Diagnostics Latest open access articles published in Diagnostics at https://www.mdpi.com/journal/diagnostics https://www.mdpi.com/journal/diagnostics MDPI en Creative Commons Attribution (CC-BY) MDPI support@mdpi.com Diagnostics, Vol. 16, Pages 3784: Diagnostic Performance of the CALLY Index in Predicting Complicated Acute Appendicitis: A Comparative Study with CAR, HALP, SII, and PIV https://www.mdpi.com/2075-4418/16/22/3784 Objective: This study aimed to evaluate the discriminatory performance of the C-reactive protein–albumin–lymphocyte (CALLY) index in complicated acute appendicitis and compare it with C-reactive protein (CRP) alone and other inflammatory indices. Materials and Methods: This single-center retrospective study included adults diagnosed with acute appendicitis between January 2021 and December 2025. Diagnostic performance was assessed using receiver operating characteristic analysis, with paired DeLong tests for AUC comparisons. Separate logistic regression models were adjusted for age and sex, and internal validation was performed using 350 bootstrap resamples. Results: Of 1733 patients screened, 1634 were included, of whom 306 (18.7%) had complicated appendicitis. CALLY and CAR each achieved an AUC of 0.782, compared with 0.778 for CRP alone. CALLY did not significantly outperform CAR (p = 0.913) or CRP (p = 0.489). Although CAR showed statistically higher discrimination than CRP (p = 0.006), the absolute AUC difference was small. CALLY demonstrated higher discrimination than HALP, SII, and PIV (all p < 0.001). In age- and sex-adjusted analysis, each doubling of CALLY was associated with lower odds of complicated appendicitis (adjusted odds ratio, 0.623; 95% CI, 0.580–0.670). The optimism-corrected AUC of the CALLY-extended model was 0.795. Conclusions: CALLY showed moderate discrimination of complicated acute appendicitis but no demonstrated advantage over CAR. Whether CALLY adds value beyond simpler laboratory measures requires further evaluation and external validation. 2026-11-14 Diagnostics, Vol. 16, Pages 3784: Diagnostic Performance of the CALLY Index in Predicting Complicated Acute Appendicitis: A Comparative Study with CAR, HALP, SII, and PIV

Diagnostics doi: 10.3390/diagnostics16223784

Authors: Mehmet Esat Ferhatlar Yavuzselim Koca Mehmet Akif Ulgen Abdurrahman Ak

Objective: This study aimed to evaluate the discriminatory performance of the C-reactive protein–albumin–lymphocyte (CALLY) index in complicated acute appendicitis and compare it with C-reactive protein (CRP) alone and other inflammatory indices. Materials and Methods: This single-center retrospective study included adults diagnosed with acute appendicitis between January 2021 and December 2025. Diagnostic performance was assessed using receiver operating characteristic analysis, with paired DeLong tests for AUC comparisons. Separate logistic regression models were adjusted for age and sex, and internal validation was performed using 350 bootstrap resamples. Results: Of 1733 patients screened, 1634 were included, of whom 306 (18.7%) had complicated appendicitis. CALLY and CAR each achieved an AUC of 0.782, compared with 0.778 for CRP alone. CALLY did not significantly outperform CAR (p = 0.913) or CRP (p = 0.489). Although CAR showed statistically higher discrimination than CRP (p = 0.006), the absolute AUC difference was small. CALLY demonstrated higher discrimination than HALP, SII, and PIV (all p < 0.001). In age- and sex-adjusted analysis, each doubling of CALLY was associated with lower odds of complicated appendicitis (adjusted odds ratio, 0.623; 95% CI, 0.580–0.670). The optimism-corrected AUC of the CALLY-extended model was 0.795. Conclusions: CALLY showed moderate discrimination of complicated acute appendicitis but no demonstrated advantage over CAR. Whether CALLY adds value beyond simpler laboratory measures requires further evaluation and external validation.

]]> Diagnostic Performance of the CALLY Index in Predicting Complicated Acute Appendicitis: A Comparative Study with CAR, HALP, SII, and PIV Mehmet Esat Ferhatlar Yavuzselim Koca Mehmet Akif Ulgen Abdurrahman Ak doi: 10.3390/diagnostics16223784 Diagnostics 2026-11-14 Diagnostics 2026-11-14 16 22 Article 3784 10.3390/diagnostics16223784 https://www.mdpi.com/2075-4418/16/22/3784 Diagnostics, Vol. 16, Pages 3783: Spontaneous Relative T1 Hyperintensity of Vertebral Metastases from Clear Cell Renal Cell Carcinoma: A Retrospective Diagnostic Accuracy Study Using the Spinal Cord as an Internal Standard https://www.mdpi.com/2075-4418/16/22/3783 Background/Objective: To evaluate the diagnostic accuracy of spontaneous T1 hyperintensity relative to the spinal cord (signal intensity ratio [SIR] > 1) for identifying vertebral metastases from clear cell renal cell carcinoma (ccRCC) among vertebral metastases of other origins, and to assess the spinal cord as an internal reference standard, as an alternative to the conventional comparison with paravertebral muscle or the intervertebral disc. Methods: This retrospective, single-centre, case–control diagnostic accuracy study was conducted at University Hospital of Messina, Italy, between January 2017 and December 2023. Patients with vertebral metastases who underwent spine MRI for radiotherapy planning were included: 11 consecutive patients with biopsy-proven ccRCC (14 lesions) and 28 patients with metastases from other solid tumours (41 lesions; convenience sample). The index test was the lesion-to-spinal-cord SIR measured on unenhanced sagittal T1-weighted fast spin-echo images acquired at 1.5 T. Two blinded neuroradiologists independently performed the measurements; lesions were classified as hyperintense relative to the spinal cord using the prespecified threshold of SIR > 1. The flow-void sign was assessed as a secondary finding. Diagnostic accuracy was calculated on a per-lesion basis with 95% confidence intervals (CIs). Results: At the SIR > 1 threshold, both readers correctly classified 13/14 ccRCC metastases and 38/41 control metastases (13 true positives, 3 false positives, 1 false negative, and 38 true negatives). Sensitivity was 92.9% (95% CI, 68.5–98.7%), specificity was 92.7% (95% CI, 80.6–97.5%), and accuracy was 92.7%. The positive and negative likelihood ratios were 12.7 (95% CI, 4.2–38.1) and 0.077 (95% CI, 0.011–0.51), respectively. The area under the receiver operating characteristic curve was 0.960 (95% CI, 0.886–1.000) for reader 1 and 0.953 (95% CI, 0.873–1.000) for reader 2. Categorical inter-reader agreement was perfect (55/55, 100%; Cohen’s kappa = 1.00). Continuous SIR measurements showed a concordance correlation coefficient of 0.896, a mean inter-reader difference of 0.003 SIR units, and no systematic bias (p > 0.9). The flow-void sign was present in 7/14 ccRCC lesions; it was not assessed in the control group. The three false-positive lesions originated from thyroid, breast, and lung cancers. Conclusions: In this preliminary series, T1 hyperintensity relative to the spinal cord was frequent in ccRCC vertebral metastases and uncommon in metastases from other tumours. Owing to the case–control design, non-consecutive controls, and small sample size, diagnostic accuracy may have been overestimated; validation in prospective, consecutive, multicentre cohorts is required. 2026-11-14 Diagnostics, Vol. 16, Pages 3783: Spontaneous Relative T1 Hyperintensity of Vertebral Metastases from Clear Cell Renal Cell Carcinoma: A Retrospective Diagnostic Accuracy Study Using the Spinal Cord as an Internal Standard

Diagnostics doi: 10.3390/diagnostics16223783

Authors: Michele Gaeta Marco Cavallaro Ludovica R. M. Lanzafame Sergio L. Vinci Agostino Tessitore Salvatore Silipigni Tommaso D’Angelo Karol Galletta Silvana Parisi Francesca Granata

Background/Objective: To evaluate the diagnostic accuracy of spontaneous T1 hyperintensity relative to the spinal cord (signal intensity ratio [SIR] > 1) for identifying vertebral metastases from clear cell renal cell carcinoma (ccRCC) among vertebral metastases of other origins, and to assess the spinal cord as an internal reference standard, as an alternative to the conventional comparison with paravertebral muscle or the intervertebral disc. Methods: This retrospective, single-centre, case–control diagnostic accuracy study was conducted at University Hospital of Messina, Italy, between January 2017 and December 2023. Patients with vertebral metastases who underwent spine MRI for radiotherapy planning were included: 11 consecutive patients with biopsy-proven ccRCC (14 lesions) and 28 patients with metastases from other solid tumours (41 lesions; convenience sample). The index test was the lesion-to-spinal-cord SIR measured on unenhanced sagittal T1-weighted fast spin-echo images acquired at 1.5 T. Two blinded neuroradiologists independently performed the measurements; lesions were classified as hyperintense relative to the spinal cord using the prespecified threshold of SIR > 1. The flow-void sign was assessed as a secondary finding. Diagnostic accuracy was calculated on a per-lesion basis with 95% confidence intervals (CIs). Results: At the SIR > 1 threshold, both readers correctly classified 13/14 ccRCC metastases and 38/41 control metastases (13 true positives, 3 false positives, 1 false negative, and 38 true negatives). Sensitivity was 92.9% (95% CI, 68.5–98.7%), specificity was 92.7% (95% CI, 80.6–97.5%), and accuracy was 92.7%. The positive and negative likelihood ratios were 12.7 (95% CI, 4.2–38.1) and 0.077 (95% CI, 0.011–0.51), respectively. The area under the receiver operating characteristic curve was 0.960 (95% CI, 0.886–1.000) for reader 1 and 0.953 (95% CI, 0.873–1.000) for reader 2. Categorical inter-reader agreement was perfect (55/55, 100%; Cohen’s kappa = 1.00). Continuous SIR measurements showed a concordance correlation coefficient of 0.896, a mean inter-reader difference of 0.003 SIR units, and no systematic bias (p > 0.9). The flow-void sign was present in 7/14 ccRCC lesions; it was not assessed in the control group. The three false-positive lesions originated from thyroid, breast, and lung cancers. Conclusions: In this preliminary series, T1 hyperintensity relative to the spinal cord was frequent in ccRCC vertebral metastases and uncommon in metastases from other tumours. Owing to the case–control design, non-consecutive controls, and small sample size, diagnostic accuracy may have been overestimated; validation in prospective, consecutive, multicentre cohorts is required.

]]> Spontaneous Relative T1 Hyperintensity of Vertebral Metastases from Clear Cell Renal Cell Carcinoma: A Retrospective Diagnostic Accuracy Study Using the Spinal Cord as an Internal Standard Michele Gaeta Marco Cavallaro Ludovica R. M. Lanzafame Sergio L. Vinci Agostino Tessitore Salvatore Silipigni Tommaso D’Angelo Karol Galletta Silvana Parisi Francesca Granata doi: 10.3390/diagnostics16223783 Diagnostics 2026-11-14 Diagnostics 2026-11-14 16 22 Article 3783 10.3390/diagnostics16223783 https://www.mdpi.com/2075-4418/16/22/3783 Diagnostics, Vol. 16, Pages 3782: Fulminant Pseudomonas aeruginosa Keratitis After Initial Improvement of Acanthamoeba Keratitis Requiring Emergency Large-Diameter Penetrating Keratoplasty https://www.mdpi.com/2075-4418/16/22/3782 A 36-year-old contact lens wearer presented with a five-day history of pain, redness, tearing, and photophobia in the right eye. Best-corrected visual acuity (BCVA) was 1.0 logMAR. Examination revealed diffuse corneal edema without ulceration. Corneal and conjunctival cultures obtained before antimicrobial treatment showed no bacterial or yeast growth, while in vivo confocal microscopy and clinical findings supported Acanthamoeba keratitis. Following seven days of topical chlorhexidine-based treatment, BCVA improved to 0.3 logMAR, and the epithelium was intact at discharge. Ten days later, the patient was readmitted with extensive stromal melting, central perforation, and light perception without projection. Both corneal and conjunctival cultures yielded Pseudomonas aeruginosa after 48 h, and subsequent antimicrobial treatment was guided by susceptibility testing. Progressive destruction necessitated emergency therapeutic penetrating keratoplasty with a 10.0 mm graft. At two months, BCVA was 1.0 logMAR, the epithelium was fully healed, and no clinical recurrence or graft rejection was observed. The biphasic course supports secondary bacterial superinfection, although initial coinfection cannot be excluded. This case highlights the importance of repeat microbiological sampling after clinical deterioration and documents short-term anatomical salvage; long-term graft survival remains undetermined. 2026-11-14 Diagnostics, Vol. 16, Pages 3782: Fulminant Pseudomonas aeruginosa Keratitis After Initial Improvement of Acanthamoeba Keratitis Requiring Emergency Large-Diameter Penetrating Keratoplasty

Diagnostics doi: 10.3390/diagnostics16223782

Authors: Wojciech Luboń Małgorzata Luboń Anna Agaś-Lange Adrian Smędowski Dorota Wyględowska-Promieńska

A 36-year-old contact lens wearer presented with a five-day history of pain, redness, tearing, and photophobia in the right eye. Best-corrected visual acuity (BCVA) was 1.0 logMAR. Examination revealed diffuse corneal edema without ulceration. Corneal and conjunctival cultures obtained before antimicrobial treatment showed no bacterial or yeast growth, while in vivo confocal microscopy and clinical findings supported Acanthamoeba keratitis. Following seven days of topical chlorhexidine-based treatment, BCVA improved to 0.3 logMAR, and the epithelium was intact at discharge. Ten days later, the patient was readmitted with extensive stromal melting, central perforation, and light perception without projection. Both corneal and conjunctival cultures yielded Pseudomonas aeruginosa after 48 h, and subsequent antimicrobial treatment was guided by susceptibility testing. Progressive destruction necessitated emergency therapeutic penetrating keratoplasty with a 10.0 mm graft. At two months, BCVA was 1.0 logMAR, the epithelium was fully healed, and no clinical recurrence or graft rejection was observed. The biphasic course supports secondary bacterial superinfection, although initial coinfection cannot be excluded. This case highlights the importance of repeat microbiological sampling after clinical deterioration and documents short-term anatomical salvage; long-term graft survival remains undetermined.

]]> Fulminant Pseudomonas aeruginosa Keratitis After Initial Improvement of Acanthamoeba Keratitis Requiring Emergency Large-Diameter Penetrating Keratoplasty Wojciech Luboń Małgorzata Luboń Anna Agaś-Lange Adrian Smędowski Dorota Wyględowska-Promieńska doi: 10.3390/diagnostics16223782 Diagnostics 2026-11-14 Diagnostics 2026-11-14 16 22 Interesting Images 3782 10.3390/diagnostics16223782 https://www.mdpi.com/2075-4418/16/22/3782 Diagnostics, Vol. 16, Pages 3781: InceptionTurkerNeXt: A Compact CNN and Deep Feature Engineering Framework for Image-Level Osteoid Osteoma Classification on Computed Tomography https://www.mdpi.com/2075-4418/16/22/3781 Background/Objectives: Osteoid osteoma (OO) is a painful benign bone tumor whose nidus is best depicted on computed tomography (CT). This exploratory study introduces InceptionTurkerNeXt, a compact convolutional neural network, and evaluates a deep feature engineering (DFE) framework built on it for image-level OO classification. Methods: The backbone was pretrained on a public 26-class multi-cancer dataset of 130,000 images. The DFE framework extracts global and patch features, selects them with cumulative weighted iterative neighborhood component analysis and classifies them with a t-algorithm-based k-nearest neighbors ensemble. The single-center OO set contains 359 axial CT images (184 OO and 175 control) from 82 patients. The primary protocol was patient-grouped 10-fold cross-validation with all selection steps fitted on the training folds. Results: The backbone reached 98.94% accuracy on the 26,000-image multi-cancer test set. Under the primary protocol, the DFE framework reached 90.81% image-level accuracy (95% confidence interval 86.35–94.71%), 91.30% sensitivity and 90.29% specificity. Patient-level voting gave 93.90% accuracy (82 patients), and a separate patient-level hold-out set gave 91.55% image-level accuracy (71 images). The earlier image-level estimate (98.33%) was optimistic by 7.52 percentage points. Four fine-tuned standard backbones reached 83.29–88.02% on the same partitions. Conclusions: The framework separated OO and control CT images with approximately 91% image-level accuracy under patient-grouped validation at one center. External multi-center validation is required before clinical use. 2026-11-14 Diagnostics, Vol. 16, Pages 3781: InceptionTurkerNeXt: A Compact CNN and Deep Feature Engineering Framework for Image-Level Osteoid Osteoma Classification on Computed Tomography

Diagnostics doi: 10.3390/diagnostics16223781

Authors: Sefa Key Anil Agar Omer Faruk Goktas Mehmet Baygin Sengul Dogan Turker Tuncer

Background/Objectives: Osteoid osteoma (OO) is a painful benign bone tumor whose nidus is best depicted on computed tomography (CT). This exploratory study introduces InceptionTurkerNeXt, a compact convolutional neural network, and evaluates a deep feature engineering (DFE) framework built on it for image-level OO classification. Methods: The backbone was pretrained on a public 26-class multi-cancer dataset of 130,000 images. The DFE framework extracts global and patch features, selects them with cumulative weighted iterative neighborhood component analysis and classifies them with a t-algorithm-based k-nearest neighbors ensemble. The single-center OO set contains 359 axial CT images (184 OO and 175 control) from 82 patients. The primary protocol was patient-grouped 10-fold cross-validation with all selection steps fitted on the training folds. Results: The backbone reached 98.94% accuracy on the 26,000-image multi-cancer test set. Under the primary protocol, the DFE framework reached 90.81% image-level accuracy (95% confidence interval 86.35–94.71%), 91.30% sensitivity and 90.29% specificity. Patient-level voting gave 93.90% accuracy (82 patients), and a separate patient-level hold-out set gave 91.55% image-level accuracy (71 images). The earlier image-level estimate (98.33%) was optimistic by 7.52 percentage points. Four fine-tuned standard backbones reached 83.29–88.02% on the same partitions. Conclusions: The framework separated OO and control CT images with approximately 91% image-level accuracy under patient-grouped validation at one center. External multi-center validation is required before clinical use.

]]> InceptionTurkerNeXt: A Compact CNN and Deep Feature Engineering Framework for Image-Level Osteoid Osteoma Classification on Computed Tomography Sefa Key Anil Agar Omer Faruk Goktas Mehmet Baygin Sengul Dogan Turker Tuncer doi: 10.3390/diagnostics16223781 Diagnostics 2026-11-14 Diagnostics 2026-11-14 16 22 Article 3781 10.3390/diagnostics16223781 https://www.mdpi.com/2075-4418/16/22/3781 Diagnostics, Vol. 16, Pages 3780: Posterior Lenticonus in a 7-Year-Old Child https://www.mdpi.com/2075-4418/16/22/3780 Posterior lenticonus is a congenital developmental defect of the ocular lens. It is an abnormal conical protrusion of the posterior lens capsule and usually occurs as an isolated defect. The diameter of the conical protrusion is typically between 2 and 7 mm. The pathogenesis of this condition is still not fully understood. Proposed but unconfirmed mechanisms include vitreous inflammation combined with excessive proliferation of posterior lens fibers, leading to lens opacification, traction on the posterior lens capsule by remnants of the hyaloid artery system, abnormalities within the tunica vasculosa lentis. The average age at diagnosis of posterior lenticonus is between 3 and 7 years. The most common complication of posterior lenticonus is amblyopia. Other frequent coexisting conditions include cataract, strabismus, and loss of central fixation. It has been observed that, over time, cataractous changes may develop within the cone and may spread to the adjacent subcapsular lens cortex. We present anterior segment optical coherence tomography (OCT) scans and a slit-lamp photograph of a 7-year-old child with posterior lenticonus, whose parents brought the patient to the Ophthalmology Clinic due to reduced visual acuity. Best corrected visual acuity (BCVA) in the right eye was 0.6. Slit-lamp examination and anterior segment OCT revealed posterior lenticonus. Pharmacological treatment was temporarily initiated, and surgery was withheld. 2026-11-14 Diagnostics, Vol. 16, Pages 3780: Posterior Lenticonus in a 7-Year-Old Child

Diagnostics doi: 10.3390/diagnostics16223780

Authors: Bogumiła Wójcik-Niklewska Natalia Kwaśniewska Jan Osicki Adrian Smędowski

Posterior lenticonus is a congenital developmental defect of the ocular lens. It is an abnormal conical protrusion of the posterior lens capsule and usually occurs as an isolated defect. The diameter of the conical protrusion is typically between 2 and 7 mm. The pathogenesis of this condition is still not fully understood. Proposed but unconfirmed mechanisms include vitreous inflammation combined with excessive proliferation of posterior lens fibers, leading to lens opacification, traction on the posterior lens capsule by remnants of the hyaloid artery system, abnormalities within the tunica vasculosa lentis. The average age at diagnosis of posterior lenticonus is between 3 and 7 years. The most common complication of posterior lenticonus is amblyopia. Other frequent coexisting conditions include cataract, strabismus, and loss of central fixation. It has been observed that, over time, cataractous changes may develop within the cone and may spread to the adjacent subcapsular lens cortex. We present anterior segment optical coherence tomography (OCT) scans and a slit-lamp photograph of a 7-year-old child with posterior lenticonus, whose parents brought the patient to the Ophthalmology Clinic due to reduced visual acuity. Best corrected visual acuity (BCVA) in the right eye was 0.6. Slit-lamp examination and anterior segment OCT revealed posterior lenticonus. Pharmacological treatment was temporarily initiated, and surgery was withheld.

]]> Posterior Lenticonus in a 7-Year-Old Child Bogumiła Wójcik-Niklewska Natalia Kwaśniewska Jan Osicki Adrian Smędowski doi: 10.3390/diagnostics16223780 Diagnostics 2026-11-14 Diagnostics 2026-11-14 16 22 Interesting Images 3780 10.3390/diagnostics16223780 https://www.mdpi.com/2075-4418/16/22/3780 Diagnostics, Vol. 16, Pages 3779: Immune Microenvironment Differences Between Upper Tract and Bladder Urothelial Carcinoma: Insights from Synchronous Disease https://www.mdpi.com/2075-4418/16/22/3779 Background/Objectives: Upper tract urothelial carcinoma (UTUC) is a rare malignancy that is more aggressive than urothelial bladder cancer (UBC). The mechanisms behind synchronous tumors at both sites remain unclear. The tumor microenvironment (TME) may influence tumor behavior. This exploratory study compares the immune landscape across UTUC-only, UTUC with synchronous UBC (UTUC-sUBC), their paired UBC (sUBC), and UBC-only tumors. Methods: Multiplex immunofluorescence (mIF) was performed to quantify CD8+ T cells, FOXP3+ regulatory T cells, CD68+ macrophages, PD-L1+ and PD-1+ cells. Comparisons were performed using Kruskal–Wallis, Mann–Whitney U, and Wilcoxon signed-rank tests. Results: UTUC-sUBC exhibited significantly lower densities of CD8+ (p = 0.013), FOXP3+, PD-L1+, and PD-1+ cells (all p < 0.001) compared to UBC-only. UTUC-only showed significantly lower densities of FOXP3+, PD-L1+, and PD-1+ cells (all p < 0.001) than UBC-only. Only PD-1+ cell density differed significantly between UTUC-sUBC and UTUC-only (p = 0.005). Paired analysis of UTUC-sUBC and matched sUBC revealed comparable immune profiles (p > 0.05). Conclusions: UTUC–sUBC tumors display an immune-depleted phenotype, distinct from the more inflamed UBC-only environment. Compared to UTUC-only, synchronous disease is distinguished by a higher PD-1+ cell density, raising the hypothesis that qualitative T-cell dysfunction, rather than quantitative infiltration, may be associated with its aggressiveness. These exploratory findings warrant validation in larger cohorts. 2026-11-14 Diagnostics, Vol. 16, Pages 3779: Immune Microenvironment Differences Between Upper Tract and Bladder Urothelial Carcinoma: Insights from Synchronous Disease

Diagnostics doi: 10.3390/diagnostics16223779

Authors: Sara Meireles Nuno Mendes Carolina Dias Ana Marques João Silva Luís Costa José Manuel Lopes Paula Soares

Background/Objectives: Upper tract urothelial carcinoma (UTUC) is a rare malignancy that is more aggressive than urothelial bladder cancer (UBC). The mechanisms behind synchronous tumors at both sites remain unclear. The tumor microenvironment (TME) may influence tumor behavior. This exploratory study compares the immune landscape across UTUC-only, UTUC with synchronous UBC (UTUC-sUBC), their paired UBC (sUBC), and UBC-only tumors. Methods: Multiplex immunofluorescence (mIF) was performed to quantify CD8+ T cells, FOXP3+ regulatory T cells, CD68+ macrophages, PD-L1+ and PD-1+ cells. Comparisons were performed using Kruskal–Wallis, Mann–Whitney U, and Wilcoxon signed-rank tests. Results: UTUC-sUBC exhibited significantly lower densities of CD8+ (p = 0.013), FOXP3+, PD-L1+, and PD-1+ cells (all p < 0.001) compared to UBC-only. UTUC-only showed significantly lower densities of FOXP3+, PD-L1+, and PD-1+ cells (all p < 0.001) than UBC-only. Only PD-1+ cell density differed significantly between UTUC-sUBC and UTUC-only (p = 0.005). Paired analysis of UTUC-sUBC and matched sUBC revealed comparable immune profiles (p > 0.05). Conclusions: UTUC–sUBC tumors display an immune-depleted phenotype, distinct from the more inflamed UBC-only environment. Compared to UTUC-only, synchronous disease is distinguished by a higher PD-1+ cell density, raising the hypothesis that qualitative T-cell dysfunction, rather than quantitative infiltration, may be associated with its aggressiveness. These exploratory findings warrant validation in larger cohorts.

]]> Immune Microenvironment Differences Between Upper Tract and Bladder Urothelial Carcinoma: Insights from Synchronous Disease Sara Meireles Nuno Mendes Carolina Dias Ana Marques João Silva Luís Costa José Manuel Lopes Paula Soares doi: 10.3390/diagnostics16223779 Diagnostics 2026-11-14 Diagnostics 2026-11-14 16 22 Article 3779 10.3390/diagnostics16223779 https://www.mdpi.com/2075-4418/16/22/3779 Diagnostics, Vol. 16, Pages 3775: Prognostic Value of Infarct-Zone Circumferential Strain by CMR Feature Tracking After Acute Myocardial Infarction Treated with Primary PCI https://www.mdpi.com/2075-4418/16/22/3775 Objectives: To evaluate the prognostic significance of CMR feature-tracking-derived peak infarct-zone circumferential strain (CSinfarct) in patients with acute myocardial infarction (AMI) following primary percutaneous coronary intervention (PPCI). Methods: Among 450 consecutive patients with AMI screened between February 2017 and March 2020, 356 patients with analyzable CMR and available follow-up were included. Global and regional myocardial strain were quantified using CMR feature tracking. Infarcted and remote myocardial segments were defined according to LGE. The primary endpoint was defined as a composite of cardiovascular death, reinfarction, and hospitalization for heart failure. Results: During a median follow-up of 44 months, 102 patients (28.7%) experienced MACE. Patients with MACE showed impaired global and regional myocardial strain and greater infarct size. In multivariable analysis, peak CSinfarct (HR, 1.08; 95% CI, 1.02–1.15; p = 0.008), GLS (HR, 1.14; 95% CI, 1.03–1.25; p = 0.008), and infarct size (HR, 1.02; 95% CI, 1.00–1.04; p = 0.046) remained independently associated with MACE. CSinfarct > −7.95% was associated with lower MACE-free survival (log-rank p < 0.001). An exploratory CMR score integrating LVEF, GLS, infarct size, and CSinfarct showed a graded increase in observed MACE rates across risk categories (9.46% to 67.65%). Conclusions: Peak CSinfarct was independently associated with long-term MACE after AMI and may provide complementary prognostic information when considered alongside conventional CMR markers. 2026-11-14 Diagnostics, Vol. 16, Pages 3775: Prognostic Value of Infarct-Zone Circumferential Strain by CMR Feature Tracking After Acute Myocardial Infarction Treated with Primary PCI

Diagnostics doi: 10.3390/diagnostics16223775

Authors: Danzeng Quyang Qingchen Zhang Huoyuan Xiao Rui Feng Wenkun Ma Zhili Xia Jingwei Pan

Objectives: To evaluate the prognostic significance of CMR feature-tracking-derived peak infarct-zone circumferential strain (CSinfarct) in patients with acute myocardial infarction (AMI) following primary percutaneous coronary intervention (PPCI). Methods: Among 450 consecutive patients with AMI screened between February 2017 and March 2020, 356 patients with analyzable CMR and available follow-up were included. Global and regional myocardial strain were quantified using CMR feature tracking. Infarcted and remote myocardial segments were defined according to LGE. The primary endpoint was defined as a composite of cardiovascular death, reinfarction, and hospitalization for heart failure. Results: During a median follow-up of 44 months, 102 patients (28.7%) experienced MACE. Patients with MACE showed impaired global and regional myocardial strain and greater infarct size. In multivariable analysis, peak CSinfarct (HR, 1.08; 95% CI, 1.02–1.15; p = 0.008), GLS (HR, 1.14; 95% CI, 1.03–1.25; p = 0.008), and infarct size (HR, 1.02; 95% CI, 1.00–1.04; p = 0.046) remained independently associated with MACE. CSinfarct > −7.95% was associated with lower MACE-free survival (log-rank p < 0.001). An exploratory CMR score integrating LVEF, GLS, infarct size, and CSinfarct showed a graded increase in observed MACE rates across risk categories (9.46% to 67.65%). Conclusions: Peak CSinfarct was independently associated with long-term MACE after AMI and may provide complementary prognostic information when considered alongside conventional CMR markers.

]]> Prognostic Value of Infarct-Zone Circumferential Strain by CMR Feature Tracking After Acute Myocardial Infarction Treated with Primary PCI Danzeng Quyang Qingchen Zhang Huoyuan Xiao Rui Feng Wenkun Ma Zhili Xia Jingwei Pan doi: 10.3390/diagnostics16223775 Diagnostics 2026-11-14 Diagnostics 2026-11-14 16 22 Article 3775 10.3390/diagnostics16223775 https://www.mdpi.com/2075-4418/16/22/3775 Diagnostics, Vol. 16, Pages 3777: Diagnostic Performance of Angiography-Derived MPFFR for Predicting Hemodynamically Significant Coronary Stenosis: A Multicenter Validation Study https://www.mdpi.com/2075-4418/16/22/3777 Background and Objectives: Angiography-derived fractional flow reserve (FFR) methods offer noninvasive alternatives to wire-based FFR for functional assessment of coronary stenosis, but their diagnostic performance requires validation. This study evaluated the diagnostic performance of artificial intelligence (AI)-driven angiography-based FFR for detecting hemodynamically significant coronary stenosis, as compared with percentage diameter stenosis (%DS) from quantitative coronary angiography (QCA), using invasive FFR as the reference standard. Methods: In this prospective, multicenter study, 189 patients (211 lesions) undergoing clinically indicated angiography were enrolled. AI-driven angiography-based FFR and %DS were derived from angiographic images and compared with invasive FFR (cutoff ≤ 0.80). Diagnostic performance was assessed using AUROC, sensitivity, specificity, and predictive values, along with correlation analysis and analysis time. Results: AI-driven angiography-based FFR showed significantly greater diagnostic performance than %DS (per-patient AUROC: 0.87 vs. 0.63, p < 0.001; per-lesion AUROC: 0.89 vs. 0.65, p < 0.001). AI-driven angiography-based FFR demonstrated higher specificity (92.7%) and positive predictive value (86.7%) than %DS (64.2% and 51.9%, respectively). AI-driven angiography-based FFR correlated strongly with invasive FFR (r = 0.746), whereas %DS showed a weak inverse correlation (r = −0.250). Median analysis time for AI-driven angiography-based FFR was 20.9 s. A gray-zone hybrid strategy (thresholds 0.73–0.83) yielded 89.8% accuracy and could reduce invasive FFR use by 57.1%. Conclusions: AI-driven angiography-based FFR demonstrated high diagnostic accuracy, strong correlation with invasive FFR, and rapid analysis time. These findings support AI-driven angiography-based FFR as a pressure-wire-free tool for physiological assessment during coronary angiography. 2026-11-14 Diagnostics, Vol. 16, Pages 3777: Diagnostic Performance of Angiography-Derived MPFFR for Predicting Hemodynamically Significant Coronary Stenosis: A Multicenter Validation Study

Diagnostics doi: 10.3390/diagnostics16223777

Authors: Houng-Beom Ahn Ju-Seung Kwun Ki-Hyun Jeon Wonjae Lee Chang-Hwan Yoon Hyun-Wook Chu Won-Woo Seo Donghoon Han Sang-Don Park Joon Hyung Doh Chang-Wook Nam Eun-Seok Shin Bon-Kwon Koo In-Ho Chae Tae-Jin Youn

Background and Objectives: Angiography-derived fractional flow reserve (FFR) methods offer noninvasive alternatives to wire-based FFR for functional assessment of coronary stenosis, but their diagnostic performance requires validation. This study evaluated the diagnostic performance of artificial intelligence (AI)-driven angiography-based FFR for detecting hemodynamically significant coronary stenosis, as compared with percentage diameter stenosis (%DS) from quantitative coronary angiography (QCA), using invasive FFR as the reference standard. Methods: In this prospective, multicenter study, 189 patients (211 lesions) undergoing clinically indicated angiography were enrolled. AI-driven angiography-based FFR and %DS were derived from angiographic images and compared with invasive FFR (cutoff ≤ 0.80). Diagnostic performance was assessed using AUROC, sensitivity, specificity, and predictive values, along with correlation analysis and analysis time. Results: AI-driven angiography-based FFR showed significantly greater diagnostic performance than %DS (per-patient AUROC: 0.87 vs. 0.63, p < 0.001; per-lesion AUROC: 0.89 vs. 0.65, p < 0.001). AI-driven angiography-based FFR demonstrated higher specificity (92.7%) and positive predictive value (86.7%) than %DS (64.2% and 51.9%, respectively). AI-driven angiography-based FFR correlated strongly with invasive FFR (r = 0.746), whereas %DS showed a weak inverse correlation (r = −0.250). Median analysis time for AI-driven angiography-based FFR was 20.9 s. A gray-zone hybrid strategy (thresholds 0.73–0.83) yielded 89.8% accuracy and could reduce invasive FFR use by 57.1%. Conclusions: AI-driven angiography-based FFR demonstrated high diagnostic accuracy, strong correlation with invasive FFR, and rapid analysis time. These findings support AI-driven angiography-based FFR as a pressure-wire-free tool for physiological assessment during coronary angiography.

]]> Diagnostic Performance of Angiography-Derived MPFFR for Predicting Hemodynamically Significant Coronary Stenosis: A Multicenter Validation Study Houng-Beom Ahn Ju-Seung Kwun Ki-Hyun Jeon Wonjae Lee Chang-Hwan Yoon Hyun-Wook Chu Won-Woo Seo Donghoon Han Sang-Don Park Joon Hyung Doh Chang-Wook Nam Eun-Seok Shin Bon-Kwon Koo In-Ho Chae Tae-Jin Youn doi: 10.3390/diagnostics16223777 Diagnostics 2026-11-14 Diagnostics 2026-11-14 16 22 Article 3777 10.3390/diagnostics16223777 https://www.mdpi.com/2075-4418/16/22/3777 Diagnostics, Vol. 16, Pages 3778: Molecular Diagnostic Surveillance, Antimicrobial Resistance, and Comorbidity Profiles in Major WHO-Critical-Priority-List Pathogens in a Saudi Tertiary-Care Hospital https://www.mdpi.com/2075-4418/16/22/3778 Background: Timely integrated diagnostic microbiology combines automated identification and antimicrobial susceptibility testing (AST) with assay-specific molecular confirmation. This allows final resistance classifications to be interpreted within one clinical workflow. The novelty of this study is the integration of these complementary diagnostic outputs with organism identity, specimen source, care setting, and available host context across a mixed-pathogen tertiary-care cohort. We characterized the distribution of major clinical priority-pathogen resistance profiles and examined clinical factors associated with high-priority resistances. Methods: This retrospective cross-sectional laboratory-based study included 847 non-duplicate clinical isolates recovered during routine care from a pre-established surveillance cohort at King Salman Specialist tertiary-care hospital in Saudi Arabia from July 2025 to July 2026. Automated organism identification/AST was combined with assay-specific GeneXpert molecular confirmation where applicable. GeneXpert SA Nasal Complete was used for Staphylococcus aureus/MRSA confirmation and Xpert Carba-R for relevant carbapenemase targets; organisms outside these target panels, including Streptococcus pyogenes and Candida spp., were characterized by routine culture and automated identification. Carbapenem resistance was defined by imipenem and/or meropenem resistance and reported as carbapenem-resistant Enterobacterales (CRE) for Klebsiella pneumoniae and Escherichia coli, carbapenem-resistant Pseudomonas aeruginosa (CRPA), and carbapenem-resistant Acinetobacter baumannii (CRAB). Methicillin-resistant Staphylococcus aureus (MRSA) was classified by cefoxitin resistance with concordant GeneXpert confirmation. Exploratory multivariable logistic regression assessed clinical factors associated with CRE and MRSA detection. Results: Gram-negative organisms accounted for 546 isolates (64.5%), Gram-positive organisms accounted for 281 (33.2%), and fungi accounted for 20 (2.4%). Klebsiella pneumoniae was most frequent (176/847; 20.8%), followed by Staphylococcus aureus (169/847; 20.0%) and Escherichia coli (156/847; 18.4%). Priority resistance was highest in Acinetobacter baumannii, with CRAB in 73/74 isolates (98.6%), followed by CRPA in 38/83 P. aeruginosa (45.8%), MRSA in 68/164 S. aureus (41.5%), CRE in 57/176 K. pneumoniae (32.4%), and CRE in 10/156 E. coli (6.4%). In the complete-case CRE model (n = 246; 38 events), K. pneumoniae had higher adjusted odds of CRE than E. coli (aOR 3.91, 95% CI 1.74–9.73; p = 0.002). In the MRSA model (n = 160; 68 events), non-urinary specimens (aOR 3.31, 95% CI 1.21–10.16; p = 0.025) and recorded comorbidity (aOR 3.40, 95% CI 1.26–9.64; p = 0.017) were independently associated with MRSA detection. Conclusions: The integrated diagnostic workflow revealed marked organism-specific differences in resistance, led by a very high CRAB burden and substantial CRPA, MRSA, and K. pneumoniae CRE. Interpreting the final laboratory classification together with organism identity, specimen source, and care setting provides a practical framework for focused diagnostic reporting, antimicrobial stewardship, and infection-control prioritization in tertiary care. 2026-11-14 Diagnostics, Vol. 16, Pages 3778: Molecular Diagnostic Surveillance, Antimicrobial Resistance, and Comorbidity Profiles in Major WHO-Critical-Priority-List Pathogens in a Saudi Tertiary-Care Hospital

Diagnostics doi: 10.3390/diagnostics16223778

Authors: Kamaleldin B. Said Ahmed A. Alsolami Ruba M. Elsaid Ahmed Khalid F. Alshammari Hamad Alshetaiwi Karima S. Al-Shurtan Naif K. Binsaleh Abdulrahman S. Alhammad Ibrahim Alshaghdali Ahmed N. Alshammari Abdulaziz S. AlQahtani Danah Althubyani Shahad A. Alhuthaili Leena S. Alharbi Norah K. Alharbi

Background: Timely integrated diagnostic microbiology combines automated identification and antimicrobial susceptibility testing (AST) with assay-specific molecular confirmation. This allows final resistance classifications to be interpreted within one clinical workflow. The novelty of this study is the integration of these complementary diagnostic outputs with organism identity, specimen source, care setting, and available host context across a mixed-pathogen tertiary-care cohort. We characterized the distribution of major clinical priority-pathogen resistance profiles and examined clinical factors associated with high-priority resistances. Methods: This retrospective cross-sectional laboratory-based study included 847 non-duplicate clinical isolates recovered during routine care from a pre-established surveillance cohort at King Salman Specialist tertiary-care hospital in Saudi Arabia from July 2025 to July 2026. Automated organism identification/AST was combined with assay-specific GeneXpert molecular confirmation where applicable. GeneXpert SA Nasal Complete was used for Staphylococcus aureus/MRSA confirmation and Xpert Carba-R for relevant carbapenemase targets; organisms outside these target panels, including Streptococcus pyogenes and Candida spp., were characterized by routine culture and automated identification. Carbapenem resistance was defined by imipenem and/or meropenem resistance and reported as carbapenem-resistant Enterobacterales (CRE) for Klebsiella pneumoniae and Escherichia coli, carbapenem-resistant Pseudomonas aeruginosa (CRPA), and carbapenem-resistant Acinetobacter baumannii (CRAB). Methicillin-resistant Staphylococcus aureus (MRSA) was classified by cefoxitin resistance with concordant GeneXpert confirmation. Exploratory multivariable logistic regression assessed clinical factors associated with CRE and MRSA detection. Results: Gram-negative organisms accounted for 546 isolates (64.5%), Gram-positive organisms accounted for 281 (33.2%), and fungi accounted for 20 (2.4%). Klebsiella pneumoniae was most frequent (176/847; 20.8%), followed by Staphylococcus aureus (169/847; 20.0%) and Escherichia coli (156/847; 18.4%). Priority resistance was highest in Acinetobacter baumannii, with CRAB in 73/74 isolates (98.6%), followed by CRPA in 38/83 P. aeruginosa (45.8%), MRSA in 68/164 S. aureus (41.5%), CRE in 57/176 K. pneumoniae (32.4%), and CRE in 10/156 E. coli (6.4%). In the complete-case CRE model (n = 246; 38 events), K. pneumoniae had higher adjusted odds of CRE than E. coli (aOR 3.91, 95% CI 1.74–9.73; p = 0.002). In the MRSA model (n = 160; 68 events), non-urinary specimens (aOR 3.31, 95% CI 1.21–10.16; p = 0.025) and recorded comorbidity (aOR 3.40, 95% CI 1.26–9.64; p = 0.017) were independently associated with MRSA detection. Conclusions: The integrated diagnostic workflow revealed marked organism-specific differences in resistance, led by a very high CRAB burden and substantial CRPA, MRSA, and K. pneumoniae CRE. Interpreting the final laboratory classification together with organism identity, specimen source, and care setting provides a practical framework for focused diagnostic reporting, antimicrobial stewardship, and infection-control prioritization in tertiary care.

]]> Molecular Diagnostic Surveillance, Antimicrobial Resistance, and Comorbidity Profiles in Major WHO-Critical-Priority-List Pathogens in a Saudi Tertiary-Care Hospital Kamaleldin B. Said Ahmed A. Alsolami Ruba M. Elsaid Ahmed Khalid F. Alshammari Hamad Alshetaiwi Karima S. Al-Shurtan Naif K. Binsaleh Abdulrahman S. Alhammad Ibrahim Alshaghdali Ahmed N. Alshammari Abdulaziz S. AlQahtani Danah Althubyani Shahad A. Alhuthaili Leena S. Alharbi Norah K. Alharbi doi: 10.3390/diagnostics16223778 Diagnostics 2026-11-14 Diagnostics 2026-11-14 16 22 Article 3778 10.3390/diagnostics16223778 https://www.mdpi.com/2075-4418/16/22/3778 Diagnostics, Vol. 16, Pages 3776: Prognostic Association of PET/CT-Defined Low Skeletal Muscle Mass in Advanced Non-Small Cell Lung Cancer Treated with Second-Line or Later Nivolumab: A Single-Center Retrospective Study https://www.mdpi.com/2075-4418/16/22/3776 Background: Low skeletal muscle mass (LSMM) may be associated with outcomes in patients with advanced non-small cell lung cancer (NSCLC) receiving immune checkpoint inhibitors. We evaluated CT-defined LSMM and survival in patients treated with second-line or later nivolumab. Methods: This single-center retrospective study included 62 patients with pretreatment 18F-FDG PET/CT. Skeletal muscle index (SMI) was measured at L3, and LSMM was defined as SMI <34.4 cm2/m2 in women and <45.4 cm2/m2 in men. Overall survival (OS) and progression-free survival (PFS) were assessed using Kaplan–Meier and Cox regression analyses. Results: LSMM was present in 32 patients (51.6%). Age ≥65 years (OR = 3.57, 95% CI 1.19–10.75; p = 0.021) and BMI <25 kg/m2 (OR = 5.67, 95% CI 1.73–18.53; p = 0.003) were associated with LSMM. Median OS was 14.23 versus 22.28 months (log-rank p = 0.049), and median PFS was 6.64 versus 14.42 months (p = 0.058), for LSMM versus no LSMM. Adjusted HRs for LSMM were 2.08 (95% CI 0.97–4.48; p = 0.062) for OS and 1.87 (95% CI 0.93–3.77; p = 0.078) for PFS. Martin and Prado SMI definitions did not reproduce these survival associations. Continuous SMI was also not associated with OS or PFS in adjusted analyses. Conclusions: The primary binary LSMM definition showed an unfavorable survival pattern, but this was not robust across alternative thresholds or continuous SMI and did not establish an independent prognostic association. 2026-11-14 Diagnostics, Vol. 16, Pages 3776: Prognostic Association of PET/CT-Defined Low Skeletal Muscle Mass in Advanced Non-Small Cell Lung Cancer Treated with Second-Line or Later Nivolumab: A Single-Center Retrospective Study

Diagnostics doi: 10.3390/diagnostics16223776

Authors: Esra Aydın Ogün Bülbül Hande Melike Bülbül Neşe Alyıldız Demet Nak Mehmet Kivrak

Background: Low skeletal muscle mass (LSMM) may be associated with outcomes in patients with advanced non-small cell lung cancer (NSCLC) receiving immune checkpoint inhibitors. We evaluated CT-defined LSMM and survival in patients treated with second-line or later nivolumab. Methods: This single-center retrospective study included 62 patients with pretreatment 18F-FDG PET/CT. Skeletal muscle index (SMI) was measured at L3, and LSMM was defined as SMI <34.4 cm2/m2 in women and <45.4 cm2/m2 in men. Overall survival (OS) and progression-free survival (PFS) were assessed using Kaplan–Meier and Cox regression analyses. Results: LSMM was present in 32 patients (51.6%). Age ≥65 years (OR = 3.57, 95% CI 1.19–10.75; p = 0.021) and BMI <25 kg/m2 (OR = 5.67, 95% CI 1.73–18.53; p = 0.003) were associated with LSMM. Median OS was 14.23 versus 22.28 months (log-rank p = 0.049), and median PFS was 6.64 versus 14.42 months (p = 0.058), for LSMM versus no LSMM. Adjusted HRs for LSMM were 2.08 (95% CI 0.97–4.48; p = 0.062) for OS and 1.87 (95% CI 0.93–3.77; p = 0.078) for PFS. Martin and Prado SMI definitions did not reproduce these survival associations. Continuous SMI was also not associated with OS or PFS in adjusted analyses. Conclusions: The primary binary LSMM definition showed an unfavorable survival pattern, but this was not robust across alternative thresholds or continuous SMI and did not establish an independent prognostic association.

]]> Prognostic Association of PET/CT-Defined Low Skeletal Muscle Mass in Advanced Non-Small Cell Lung Cancer Treated with Second-Line or Later Nivolumab: A Single-Center Retrospective Study Esra Aydın Ogün Bülbül Hande Melike Bülbül Neşe Alyıldız Demet Nak Mehmet Kivrak doi: 10.3390/diagnostics16223776 Diagnostics 2026-11-14 Diagnostics 2026-11-14 16 22 Article 3776 10.3390/diagnostics16223776 https://www.mdpi.com/2075-4418/16/22/3776 Diagnostics, Vol. 16, Pages 3774: Word-Anchored Eye-Movement Measures for Interpretable and Calibration-Robust Dyslexia Screening on the ETDD70 Dataset https://www.mdpi.com/2075-4418/16/22/3774 Background/Objectives:Eye-tracking models for dyslexia screening usually describe gaze in screen coordinates, although dyslexia is a difficulty with words and letters. We aimed to develop an interpretable word-anchored screening approach that is robust to calibration error. Methods: We analysed the public ETDD70 dataset (70 Czech children, 35 with dyslexia). The position of all 292 stimulus words was recovered exactly from the released landing positions, and every fixation was assigned to a word and letter. Each child was described by word-level reading measures, linguistic sensitivities and saccade geometry in letters (LexiGaze), complemented by empirical-Bayes profiles and a generative likelihood-ratio classifier. Models were evaluated by nested participant-level cross-validation and under simulated gaze error. Results: The resulting word assignment matched the dataset labels for 99.99% of fixations. Dyslexia was associated with 42% longer gaze durations on meaningful text and with an exaggerated word-length effect on fixation counts. LexiGaze reached a balanced accuracy of 82.57% (AUC 0.913) and the generative classifier an AUC of 0.938, comparable to existing descriptors. Under gaze noise of 30 pixels, pixel-based geometry lost 23.4 points of balanced accuracy and LexiGaze 6.0 (direct comparison p = 0.053); with the recorded vertical coordinates, without drift correction, they lost 5.1 and 0.3 points. Conclusions: Word-anchored measures match existing accuracy while being interpretable in psycholinguistic terms and less sensitive to calibration error. 2026-11-14 Diagnostics, Vol. 16, Pages 3774: Word-Anchored Eye-Movement Measures for Interpretable and Calibration-Robust Dyslexia Screening on the ETDD70 Dataset

Diagnostics doi: 10.3390/diagnostics16223774

Authors: Kais Khaldi Hamed Alshammari

Background/Objectives:Eye-tracking models for dyslexia screening usually describe gaze in screen coordinates, although dyslexia is a difficulty with words and letters. We aimed to develop an interpretable word-anchored screening approach that is robust to calibration error. Methods: We analysed the public ETDD70 dataset (70 Czech children, 35 with dyslexia). The position of all 292 stimulus words was recovered exactly from the released landing positions, and every fixation was assigned to a word and letter. Each child was described by word-level reading measures, linguistic sensitivities and saccade geometry in letters (LexiGaze), complemented by empirical-Bayes profiles and a generative likelihood-ratio classifier. Models were evaluated by nested participant-level cross-validation and under simulated gaze error. Results: The resulting word assignment matched the dataset labels for 99.99% of fixations. Dyslexia was associated with 42% longer gaze durations on meaningful text and with an exaggerated word-length effect on fixation counts. LexiGaze reached a balanced accuracy of 82.57% (AUC 0.913) and the generative classifier an AUC of 0.938, comparable to existing descriptors. Under gaze noise of 30 pixels, pixel-based geometry lost 23.4 points of balanced accuracy and LexiGaze 6.0 (direct comparison p = 0.053); with the recorded vertical coordinates, without drift correction, they lost 5.1 and 0.3 points. Conclusions: Word-anchored measures match existing accuracy while being interpretable in psycholinguistic terms and less sensitive to calibration error.

]]> Word-Anchored Eye-Movement Measures for Interpretable and Calibration-Robust Dyslexia Screening on the ETDD70 Dataset Kais Khaldi Hamed Alshammari doi: 10.3390/diagnostics16223774 Diagnostics 2026-11-14 Diagnostics 2026-11-14 16 22 Article 3774 10.3390/diagnostics16223774 https://www.mdpi.com/2075-4418/16/22/3774 Diagnostics, Vol. 16, Pages 3773: Machine-Learning Prediction of Pediatric Thyroid Nodule Malignancy Using Structured Nodule and Cervical Lymph-Node Ultrasonographic Features https://www.mdpi.com/2075-4418/16/22/3773 Background/Objectives: Pediatric thyroid nodules carry a higher malignancy risk and more frequent regional cervical lymph-node involvement than adult nodules, making individualized pre-biopsy risk assessment particularly important. We aimed to develop and temporally validate a machine-learning model integrating routinely available thyroid-nodule and cervical lymph-node ultrasonographic features for malignancy-risk estimation in children. Methods: This retrospective single-center study at a tertiary pediatric referral center included consecutive patients aged 18 years or younger undergoing biopsy-based diagnostic evaluation between January 2019 and August 2025. The cohort comprised 195 patients with 221 nodules. Six candidate algorithms were evaluated using patient-grouped nested cross-validation. The selected XGBoost model integrated structured nodule and regional cervical lymph-node ultrasonographic features and was evaluated using discrimination, precision–recall performance, probability accuracy, calibration, and threshold-dependent operating characteristics. ACR TI-RADS served as a secondary standardized comparator. Results: Overall, 151 of 221 nodules (68.3%) were malignant, including 32 of 48 nodules (66.7%) in the temporal validation cohort. The final model achieved an AUROC of 0.973 (95% CI, 0.919–1.000), an AUPRC of 0.986 (95% CI, 0.954–1.000), a Brier score of 0.071 (95% CI, 0.030–0.126), a sensitivity of 84.4%, and a specificity of 87.5%. For comparison, the ACR TI-RADS total score yielded an AUROC of 0.906, while the TR5-positive and TR4/5-positive strategies yielded sensitivities of 84.4% and 93.8% and specificities of 87.5% and 56.2%, respectively. Conclusions: Integrating thyroid-nodule and cervical lymph-node ultrasonographic features enabled individualized malignancy-risk estimation in this selected pediatric biopsy-evaluation cohort. The continuous risk estimate may complement established sonographic assessment as an adjunct to comprehensive diagnostic evaluation. Prospective multicenter external validation is required before broader clinical application. 2026-11-14 Diagnostics, Vol. 16, Pages 3773: Machine-Learning Prediction of Pediatric Thyroid Nodule Malignancy Using Structured Nodule and Cervical Lymph-Node Ultrasonographic Features

Diagnostics doi: 10.3390/diagnostics16223773

Authors: Jiaojiao Ding Xiao Zhang Yue Chang Saikang Tang Jiabin Wan Qiaoyin Liu Wenyuan Shi Xin Ni

Background/Objectives: Pediatric thyroid nodules carry a higher malignancy risk and more frequent regional cervical lymph-node involvement than adult nodules, making individualized pre-biopsy risk assessment particularly important. We aimed to develop and temporally validate a machine-learning model integrating routinely available thyroid-nodule and cervical lymph-node ultrasonographic features for malignancy-risk estimation in children. Methods: This retrospective single-center study at a tertiary pediatric referral center included consecutive patients aged 18 years or younger undergoing biopsy-based diagnostic evaluation between January 2019 and August 2025. The cohort comprised 195 patients with 221 nodules. Six candidate algorithms were evaluated using patient-grouped nested cross-validation. The selected XGBoost model integrated structured nodule and regional cervical lymph-node ultrasonographic features and was evaluated using discrimination, precision–recall performance, probability accuracy, calibration, and threshold-dependent operating characteristics. ACR TI-RADS served as a secondary standardized comparator. Results: Overall, 151 of 221 nodules (68.3%) were malignant, including 32 of 48 nodules (66.7%) in the temporal validation cohort. The final model achieved an AUROC of 0.973 (95% CI, 0.919–1.000), an AUPRC of 0.986 (95% CI, 0.954–1.000), a Brier score of 0.071 (95% CI, 0.030–0.126), a sensitivity of 84.4%, and a specificity of 87.5%. For comparison, the ACR TI-RADS total score yielded an AUROC of 0.906, while the TR5-positive and TR4/5-positive strategies yielded sensitivities of 84.4% and 93.8% and specificities of 87.5% and 56.2%, respectively. Conclusions: Integrating thyroid-nodule and cervical lymph-node ultrasonographic features enabled individualized malignancy-risk estimation in this selected pediatric biopsy-evaluation cohort. The continuous risk estimate may complement established sonographic assessment as an adjunct to comprehensive diagnostic evaluation. Prospective multicenter external validation is required before broader clinical application.

]]> Machine-Learning Prediction of Pediatric Thyroid Nodule Malignancy Using Structured Nodule and Cervical Lymph-Node Ultrasonographic Features Jiaojiao Ding Xiao Zhang Yue Chang Saikang Tang Jiabin Wan Qiaoyin Liu Wenyuan Shi Xin Ni doi: 10.3390/diagnostics16223773 Diagnostics 2026-11-14 Diagnostics 2026-11-14 16 22 Article 3773 10.3390/diagnostics16223773 https://www.mdpi.com/2075-4418/16/22/3773 Diagnostics, Vol. 16, Pages 3772: Dual-Timepoint 18F-FDG PET/CT Radiomics for Treatment Response in Breast Cancer: A Two-Center External Validation Study https://www.mdpi.com/2075-4418/16/22/3772 Background: This study investigated the incremental value of radiomic features derived from 18F-FDG PET/CT over clinicopathological characteristics and conventional PET parameters for predicting and assessing metabolic treatment response in breast cancer, using independent external validation. Materials and Methods: This retrospective, two-center study included 153 patients with metastatic or non-metastatic breast cancer representing different biological subtypes, all of whom underwent systemic treatment and paired pretreatment and post-treatment 18F-FDG PET/CT. The development cohort comprised 115 patients, while 38 patients from a second institution formed the external validation cohort. The endpoint was complete metabolic response (CMR) of the primary breast tumor. Scenario A examined pretreatment prediction of CMR using baseline variables, whereas Scenario B assessed imaging-defined CMR using post-treatment and longitudinal PET/CT parameters. Models were developed using L1-regularized logistic regression with five-fold stratified cross-validation and evaluated in the external cohort without refitting. Results: Primary-tumor CMR was observed in 14 of 115 patients (12.2%) in the development cohort and 18 of 38 patients (47.4%) in the external cohort. In Scenario A, the multimodal model incorporating radiomics achieved an external validation AUC of 0.747 (95% CI, 0.577–0.887), compared with 0.636 for the model combining clinicopathological variables and conventional PET parameters (ΔAUC = 0.111). Compared with the clinical-only model (AUC = 0.658), the multimodal model improved discrimination by 0.089, although the difference was not statistically significant (DeLong p = 0.146). In Scenario B, conventional post-treatment PET parameters achieved an AUC of 0.986 (95% CI, 0.953–1.000). Adding radiomic features did not improve discrimination (AUC = 0.986). Conclusions: Pretreatment radiomics showed potential additional value for predicting primary-tumor CMR, although the improvement in discrimination was not statistically significant. After treatment, conventional PET parameters provided high discrimination for imaging-defined primary-tumor CMR, with no further improvement from radiomics. These findings require confirmation in larger, prospective cohorts before their clinical application. 2026-11-14 Diagnostics, Vol. 16, Pages 3772: Dual-Timepoint 18F-FDG PET/CT Radiomics for Treatment Response in Breast Cancer: A Two-Center External Validation Study

Diagnostics doi: 10.3390/diagnostics16223772

Authors: Ozcan Senmevsim Filiz Hatipoglu Emir Gökhan Kahraman Ismail F. Ozsakarya

Background: This study investigated the incremental value of radiomic features derived from 18F-FDG PET/CT over clinicopathological characteristics and conventional PET parameters for predicting and assessing metabolic treatment response in breast cancer, using independent external validation. Materials and Methods: This retrospective, two-center study included 153 patients with metastatic or non-metastatic breast cancer representing different biological subtypes, all of whom underwent systemic treatment and paired pretreatment and post-treatment 18F-FDG PET/CT. The development cohort comprised 115 patients, while 38 patients from a second institution formed the external validation cohort. The endpoint was complete metabolic response (CMR) of the primary breast tumor. Scenario A examined pretreatment prediction of CMR using baseline variables, whereas Scenario B assessed imaging-defined CMR using post-treatment and longitudinal PET/CT parameters. Models were developed using L1-regularized logistic regression with five-fold stratified cross-validation and evaluated in the external cohort without refitting. Results: Primary-tumor CMR was observed in 14 of 115 patients (12.2%) in the development cohort and 18 of 38 patients (47.4%) in the external cohort. In Scenario A, the multimodal model incorporating radiomics achieved an external validation AUC of 0.747 (95% CI, 0.577–0.887), compared with 0.636 for the model combining clinicopathological variables and conventional PET parameters (ΔAUC = 0.111). Compared with the clinical-only model (AUC = 0.658), the multimodal model improved discrimination by 0.089, although the difference was not statistically significant (DeLong p = 0.146). In Scenario B, conventional post-treatment PET parameters achieved an AUC of 0.986 (95% CI, 0.953–1.000). Adding radiomic features did not improve discrimination (AUC = 0.986). Conclusions: Pretreatment radiomics showed potential additional value for predicting primary-tumor CMR, although the improvement in discrimination was not statistically significant. After treatment, conventional PET parameters provided high discrimination for imaging-defined primary-tumor CMR, with no further improvement from radiomics. These findings require confirmation in larger, prospective cohorts before their clinical application.

]]> Dual-Timepoint 18F-FDG PET/CT Radiomics for Treatment Response in Breast Cancer: A Two-Center External Validation Study Ozcan Senmevsim Filiz Hatipoglu Emir Gökhan Kahraman Ismail F. Ozsakarya doi: 10.3390/diagnostics16223772 Diagnostics 2026-11-14 Diagnostics 2026-11-14 16 22 Article 3772 10.3390/diagnostics16223772 https://www.mdpi.com/2075-4418/16/22/3772 Diagnostics, Vol. 16, Pages 3771: Enhancing HCC Surveillance with GPTs: Computational, Prompt Engineering, and Multimodal Strategies https://www.mdpi.com/2075-4418/16/22/3771 Objectives: Research on applying Large Language Models to hepatocellular carcinoma (HCC) surveillance is limited. We aimed to develop customized GPTs for HCC surveillance and evaluate their performance in predicting HCC risk and providing surveillance recommendations. Materials and Methods: This single-center retrospective study included 376 patients with 797 surveillance visits between January 2014 and March 2023 for evaluation. We developed GPTs by integrating medical expert knowledge and optimized it through three strategies: (1) boosting computational capabilities via code enhancements and in-context learning; (2) enhancing reasoning abilities through prompt engineering; (3) increasing clinical applicability by integrating multimodal clinical data. We assessed the predictive performance of GPTs across different modalities and the efficiency and clinical appropriateness of their surveillance recommendations. Results: Combining in-context learning with code instruction improved HCC risk score calculation accuracy to 97.4%, compared with 90.2% using code instruction alone and 31.1% using default calculation (both p < 0.001). For the five-year HCC prediction, the second chain-of-thought (CoT2) strategy improved sensitivity from 65.3% to 77.6% (p = 0.037), with a numerically higher AUC compared with original GPTs (0.782 vs. 0.731, all p = 0.095). Dual-modality and multi-modality GPTs outperformed traditional scores in predicting HCC (AUC: 0.839 and 0.840 vs. 0.737–0.762, all p < 0.05). Among patients who developed HCC, multi-modality GPTs achieved the highest surveillance efficiency index (2.34) and an estimated earlier detection time of 5.43 months, compared with 2.22 and 4.49 months, respectively, under AASLD-based surveillance, with a higher estimated annual CT/MRI examination frequency (1.46 vs. 0.98). Conclusions: Customized GPTs showed promise for HCC risk prediction and individualized surveillance, warranting further prospective multicenter validation. 2026-11-14 Diagnostics, Vol. 16, Pages 3771: Enhancing HCC Surveillance with GPTs: Computational, Prompt Engineering, and Multimodal Strategies

Diagnostics doi: 10.3390/diagnostics16223771

Authors: Shao-Hong Wu Xin-Xin Lin Yue Zeng Ya-Dan Lin Rui-Fang Lu Xiao-Fang Guo Zhe Zhang Ji-Hang Chen Lai-Na Wei Meng-Yao Cai Ying Ban Ming-De Li Wei Wang Li-Da Chen Yang-Yang Lei Mei-Qing Cheng

Objectives: Research on applying Large Language Models to hepatocellular carcinoma (HCC) surveillance is limited. We aimed to develop customized GPTs for HCC surveillance and evaluate their performance in predicting HCC risk and providing surveillance recommendations. Materials and Methods: This single-center retrospective study included 376 patients with 797 surveillance visits between January 2014 and March 2023 for evaluation. We developed GPTs by integrating medical expert knowledge and optimized it through three strategies: (1) boosting computational capabilities via code enhancements and in-context learning; (2) enhancing reasoning abilities through prompt engineering; (3) increasing clinical applicability by integrating multimodal clinical data. We assessed the predictive performance of GPTs across different modalities and the efficiency and clinical appropriateness of their surveillance recommendations. Results: Combining in-context learning with code instruction improved HCC risk score calculation accuracy to 97.4%, compared with 90.2% using code instruction alone and 31.1% using default calculation (both p < 0.001). For the five-year HCC prediction, the second chain-of-thought (CoT2) strategy improved sensitivity from 65.3% to 77.6% (p = 0.037), with a numerically higher AUC compared with original GPTs (0.782 vs. 0.731, all p = 0.095). Dual-modality and multi-modality GPTs outperformed traditional scores in predicting HCC (AUC: 0.839 and 0.840 vs. 0.737–0.762, all p < 0.05). Among patients who developed HCC, multi-modality GPTs achieved the highest surveillance efficiency index (2.34) and an estimated earlier detection time of 5.43 months, compared with 2.22 and 4.49 months, respectively, under AASLD-based surveillance, with a higher estimated annual CT/MRI examination frequency (1.46 vs. 0.98). Conclusions: Customized GPTs showed promise for HCC risk prediction and individualized surveillance, warranting further prospective multicenter validation.

]]> Enhancing HCC Surveillance with GPTs: Computational, Prompt Engineering, and Multimodal Strategies Shao-Hong Wu Xin-Xin Lin Yue Zeng Ya-Dan Lin Rui-Fang Lu Xiao-Fang Guo Zhe Zhang Ji-Hang Chen Lai-Na Wei Meng-Yao Cai Ying Ban Ming-De Li Wei Wang Li-Da Chen Yang-Yang Lei Mei-Qing Cheng doi: 10.3390/diagnostics16223771 Diagnostics 2026-11-14 Diagnostics 2026-11-14 16 22 Article 3771 10.3390/diagnostics16223771 https://www.mdpi.com/2075-4418/16/22/3771 Diagnostics, Vol. 16, Pages 3770: Topical Therapy for Keratinocyte Carcinoma—Systematic Review and Network Meta-Analysis of Efficacy and Patient Follow-Up Using Non-Invasive Imaging Techniques https://www.mdpi.com/2075-4418/16/22/3770 Background/Objectives: Topical therapies, primarily imiquimod (IMQ) and 5-fluorouracil (5-FU), have emerged as valuable treatment options in non-melanoma skin cancers (NMSC) due to their facile administration and minimal systemic reactions, especially for patients who are poor surgical candidates. This systematic review evaluates the clinical and histologic clearance rates, recurrence rates as well as the utility of non-invasive imaging modalities in the diagnosis and monitoring of basal cell carcinomas (BCC) and cutaneous squamous cell carcinoma (SCC). Methods: The systematic search was conducted in PubMed, Web of Science and Scopus to identify studies assessing the efficacy of topical therapies in BCC and SCC by clinical examination, histopathologic analysis or non-invasive imaging techniques. Articles in which at least ten lesions were evaluated were included. Risk of bias was assessed using validated tools adapted to study design. A network meta-analysis was performed on trials which provided at least one within-trial comparison. Results: Seventy-eight papers encompassing 5066 BCC and 1081 SCC were included in our analysis. The network meta-analysis was constructed from 14 trials, comprising 1633 lesions, 17 treatment nodes, 57 direct treatment comparisons and 12 designs. Favorable clearance rates were reported not only in superficial BCC (sBCC) and Bowen’s disease (BD), but also in nodular BCC (nBCC) and invasive SCC (invSCC), suggesting that these therapies may be an effective approach in selected patients with aggressive tumors. Relapse rates remain higher than after surgical excision, highlighting the need for patient follow-up. Reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) improved the detection of recurrent and relapsed tumors in comparison to clinical and dermoscopic examination alone and correlated significantly with histopathological findings, proving that these modalities can contribute significantly to diagnosis and monitoring. Conclusions: Our systematic review demonstrates the efficacy of topical therapies, especially IMQ and 5-FU, in selected cases of sBCC and BD. Results should, however, be interpreted with caution, given the small number of studies included in the network and the heterogeneity of treatment regimens. 2026-11-13 Diagnostics, Vol. 16, Pages 3770: Topical Therapy for Keratinocyte Carcinoma—Systematic Review and Network Meta-Analysis of Efficacy and Patient Follow-Up Using Non-Invasive Imaging Techniques

Diagnostics doi: 10.3390/diagnostics16223770

Authors: Mara Filip Mircea Negrutiu Sorina Danescu Camelia Alexandra Coada Adrian Baican

Background/Objectives: Topical therapies, primarily imiquimod (IMQ) and 5-fluorouracil (5-FU), have emerged as valuable treatment options in non-melanoma skin cancers (NMSC) due to their facile administration and minimal systemic reactions, especially for patients who are poor surgical candidates. This systematic review evaluates the clinical and histologic clearance rates, recurrence rates as well as the utility of non-invasive imaging modalities in the diagnosis and monitoring of basal cell carcinomas (BCC) and cutaneous squamous cell carcinoma (SCC). Methods: The systematic search was conducted in PubMed, Web of Science and Scopus to identify studies assessing the efficacy of topical therapies in BCC and SCC by clinical examination, histopathologic analysis or non-invasive imaging techniques. Articles in which at least ten lesions were evaluated were included. Risk of bias was assessed using validated tools adapted to study design. A network meta-analysis was performed on trials which provided at least one within-trial comparison. Results: Seventy-eight papers encompassing 5066 BCC and 1081 SCC were included in our analysis. The network meta-analysis was constructed from 14 trials, comprising 1633 lesions, 17 treatment nodes, 57 direct treatment comparisons and 12 designs. Favorable clearance rates were reported not only in superficial BCC (sBCC) and Bowen’s disease (BD), but also in nodular BCC (nBCC) and invasive SCC (invSCC), suggesting that these therapies may be an effective approach in selected patients with aggressive tumors. Relapse rates remain higher than after surgical excision, highlighting the need for patient follow-up. Reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) improved the detection of recurrent and relapsed tumors in comparison to clinical and dermoscopic examination alone and correlated significantly with histopathological findings, proving that these modalities can contribute significantly to diagnosis and monitoring. Conclusions: Our systematic review demonstrates the efficacy of topical therapies, especially IMQ and 5-FU, in selected cases of sBCC and BD. Results should, however, be interpreted with caution, given the small number of studies included in the network and the heterogeneity of treatment regimens.

]]> Topical Therapy for Keratinocyte Carcinoma—Systematic Review and Network Meta-Analysis of Efficacy and Patient Follow-Up Using Non-Invasive Imaging Techniques Mara Filip Mircea Negrutiu Sorina Danescu Camelia Alexandra Coada Adrian Baican doi: 10.3390/diagnostics16223770 Diagnostics 2026-11-13 Diagnostics 2026-11-13 16 22 Systematic Review 3770 10.3390/diagnostics16223770 https://www.mdpi.com/2075-4418/16/22/3770 Diagnostics, Vol. 16, Pages 3769: Imaging the Vascular Component of Primary Open-Angle Glaucoma: From Pathophysiology to Novel Hemodynamic Biomarkers https://www.mdpi.com/2075-4418/16/22/3769 Primary open-angle glaucoma (POAG) is the leading cause of irreversible blindness worldwide. Intraocular pressure (IOP) is its only validated therapeutic target, yet some patients progress despite controlled IOP, sustaining interest in a vascular contribution. This narrative review summarizes the anatomy and autoregulation of the optic nerve head circulation, the evidence linking low ocular perfusion pressure, impaired autoregulation and endothelial dysfunction to POAG, and the imaging modalities used to assess ocular hemodynamics. Color Doppler imaging consistently shows reduced retrobulbar flow velocities, particularly end-diastolic, and increased resistive indices, whereas OCT angiography shows reduced peripapillary and macular vessel density correlated with structural and functional damage. However, most evidence is cross-sectional and associative, and cannot establish whether hypoperfusion causes or follows retinal ganglion cell loss. No hemodynamic biomarker has been validated for clinical decision-making, and evidence of prognostic value beyond conventional structural and functional assessment remains inconsistent. Laser Doppler holography, a contactless technique providing pulsatile retinal blood flow waveforms, is presented as an emerging tool whose glaucoma-specific evidence is currently limited to a pilot study of four eyes. Vascular biomarkers therefore remain research tools pending standardized acquisition, normative databases and longitudinal validation. 2026-11-13 Diagnostics, Vol. 16, Pages 3769: Imaging the Vascular Component of Primary Open-Angle Glaucoma: From Pathophysiology to Novel Hemodynamic Biomarkers

Diagnostics doi: 10.3390/diagnostics16223769

Authors: Philippe Genin Charles Madar Juliette Buffault Christophe Baudouin Antoine Labbé Paul Bastelica

Primary open-angle glaucoma (POAG) is the leading cause of irreversible blindness worldwide. Intraocular pressure (IOP) is its only validated therapeutic target, yet some patients progress despite controlled IOP, sustaining interest in a vascular contribution. This narrative review summarizes the anatomy and autoregulation of the optic nerve head circulation, the evidence linking low ocular perfusion pressure, impaired autoregulation and endothelial dysfunction to POAG, and the imaging modalities used to assess ocular hemodynamics. Color Doppler imaging consistently shows reduced retrobulbar flow velocities, particularly end-diastolic, and increased resistive indices, whereas OCT angiography shows reduced peripapillary and macular vessel density correlated with structural and functional damage. However, most evidence is cross-sectional and associative, and cannot establish whether hypoperfusion causes or follows retinal ganglion cell loss. No hemodynamic biomarker has been validated for clinical decision-making, and evidence of prognostic value beyond conventional structural and functional assessment remains inconsistent. Laser Doppler holography, a contactless technique providing pulsatile retinal blood flow waveforms, is presented as an emerging tool whose glaucoma-specific evidence is currently limited to a pilot study of four eyes. Vascular biomarkers therefore remain research tools pending standardized acquisition, normative databases and longitudinal validation.

]]> Imaging the Vascular Component of Primary Open-Angle Glaucoma: From Pathophysiology to Novel Hemodynamic Biomarkers Philippe Genin Charles Madar Juliette Buffault Christophe Baudouin Antoine Labbé Paul Bastelica doi: 10.3390/diagnostics16223769 Diagnostics 2026-11-13 Diagnostics 2026-11-13 16 22 Review 3769 10.3390/diagnostics16223769 https://www.mdpi.com/2075-4418/16/22/3769 Diagnostics, Vol. 16, Pages 3768: The Impact of MTHFR Gene Polymorphisms on Cerebral Small and Large Vessel Disease, Vascular Cognitive Impairment and Cerebral Volumetric Reduction https://www.mdpi.com/2075-4418/16/22/3768 Objective: The study aims to evaluate the association of methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms with cerebral small vessel disease (CSVD), cerebral large vessel disease (CLVD), vascular cognitive impairment (VCI) and global and regional brain volumes. Methods: Clinical, laboratory, neuroimaging, volumetric, cognitive and MTHFR genotyping data were retrospectively collected from 62 patients with CSVD (n = 40) or CLVD (n = 22), all carriers of at least one MTHFR variant. Brain volumes were compared between patients with VCI carrying C677T (n = 30) and patients without VCI (n = 32). Analyses were repeated in the open-source platform jamovi and p-values were corrected for multiple comparisons with the Holm procedure. Results: The cohort comprised 41 women and 21 men (mean age 56.9 years). The CT and TT genotypes of C677T, the AC and CC genotypes of A1298C, blood pressure, total cholesterol and triglycerides differed between CSVD and CLVD at the unadjusted level (p < 0.05), but none of these differences remained significant after Holm correction. VCI carriers of C677T showed lower white matter (332.9 ± 25.5 vs. 437.9 ± 35.7 cm3) and gray matter volumes (626.0 ± 45.7 vs. 699.7 ± 51.5 cm3), higher cerebrospinal fluid volume (238.3 ± 42.2 vs. 197.1 ± 24.8 cm3) and reduced hippocampal, amygdalar, thalamic, superior frontal, middle temporal, entorhinal, parahippocampal and middle occipital volumes (all Holm-adjusted p < 0.05). Conclusions: Differences in MTHFR genotype distribution between CSVD and CLVD were not robust to correction for multiple testing, whereas VCI carriers of C677T showed global and selective regional volume loss that withstood correction. MTHFR variants are susceptibility markers rather than direct causes of vascular injury; these associations, which could not be adjusted for comorbid vascular risk factors or for concomitant neurodegenerative pathology, require confirmation in prospective, controlled studies with homocysteine measurements. 2026-11-13 Diagnostics, Vol. 16, Pages 3768: The Impact of MTHFR Gene Polymorphisms on Cerebral Small and Large Vessel Disease, Vascular Cognitive Impairment and Cerebral Volumetric Reduction

Diagnostics doi: 10.3390/diagnostics16223768

Authors: Andreea Alexandra Gogu Any Axelerad Anca Elena Gogu Marius Benta Silviu Docu-Axelerad Oana Neda-Stepan Ana Cristina Bredicean

Objective: The study aims to evaluate the association of methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms with cerebral small vessel disease (CSVD), cerebral large vessel disease (CLVD), vascular cognitive impairment (VCI) and global and regional brain volumes. Methods: Clinical, laboratory, neuroimaging, volumetric, cognitive and MTHFR genotyping data were retrospectively collected from 62 patients with CSVD (n = 40) or CLVD (n = 22), all carriers of at least one MTHFR variant. Brain volumes were compared between patients with VCI carrying C677T (n = 30) and patients without VCI (n = 32). Analyses were repeated in the open-source platform jamovi and p-values were corrected for multiple comparisons with the Holm procedure. Results: The cohort comprised 41 women and 21 men (mean age 56.9 years). The CT and TT genotypes of C677T, the AC and CC genotypes of A1298C, blood pressure, total cholesterol and triglycerides differed between CSVD and CLVD at the unadjusted level (p < 0.05), but none of these differences remained significant after Holm correction. VCI carriers of C677T showed lower white matter (332.9 ± 25.5 vs. 437.9 ± 35.7 cm3) and gray matter volumes (626.0 ± 45.7 vs. 699.7 ± 51.5 cm3), higher cerebrospinal fluid volume (238.3 ± 42.2 vs. 197.1 ± 24.8 cm3) and reduced hippocampal, amygdalar, thalamic, superior frontal, middle temporal, entorhinal, parahippocampal and middle occipital volumes (all Holm-adjusted p < 0.05). Conclusions: Differences in MTHFR genotype distribution between CSVD and CLVD were not robust to correction for multiple testing, whereas VCI carriers of C677T showed global and selective regional volume loss that withstood correction. MTHFR variants are susceptibility markers rather than direct causes of vascular injury; these associations, which could not be adjusted for comorbid vascular risk factors or for concomitant neurodegenerative pathology, require confirmation in prospective, controlled studies with homocysteine measurements.

]]> The Impact of MTHFR Gene Polymorphisms on Cerebral Small and Large Vessel Disease, Vascular Cognitive Impairment and Cerebral Volumetric Reduction Andreea Alexandra Gogu Any Axelerad Anca Elena Gogu Marius Benta Silviu Docu-Axelerad Oana Neda-Stepan Ana Cristina Bredicean doi: 10.3390/diagnostics16223768 Diagnostics 2026-11-13 Diagnostics 2026-11-13 16 22 Article 3768 10.3390/diagnostics16223768 https://www.mdpi.com/2075-4418/16/22/3768 Diagnostics, Vol. 16, Pages 3767: Beyond Epithelial Thickness: Comprehensive Profiling of Corneal Epithelial Remodeling and Its Diagnostic Value Across Keratoconus Severity: The Noor Multimodal Corneal Imaging Study (NMCIS) https://www.mdpi.com/2075-4418/16/22/3767 Background: Keratoconus causes characteristic spatial epithelial remodeling that may not be captured by conventional thickness measurements. Novel morphometric indices from MS-39 AS-OCT may better characterize these changes. Purpose: We aimed to evaluate novel MS-39 AS-OCT epithelial remodeling indices and compare their diagnostic accuracy with epithelial thickness and Pentacam tomography across the keratoconus spectrum, using an objective reference standard. Methods: This retrospective diagnostic accuracy study included 1319 eyes of 1286 patients with same-day Pentacam and MS-39 imaging at Noor Eye Hospital (2023–2025). Eyes were classified from the clinical records and Pentacam front-surface indices, without use of any epithelial data, as normal (n = 861), forme fruste keratoconus (FFKC; topographically normal fellow eye of very asymmetric ectasia; n = 40) or definite keratoconus (n = 418), graded mild, moderate or severe with the ABCD system. Generalized estimating equations, receiver operating characteristic (ROC) analysis with DeLong confidence intervals and cross-validated cut-offs, and bootstrap-validated logistic models were used. Results: The central epithelial remodeling index (CERI) and central epithelial thickness range (CETR) increased with severity (+0.137 and +6.13 µm per severity grade; both p < 0.001). For definite keratoconus, CERI (AUC 0.932; 95% CI 0.913–0.948) and CETR (0.930) outperformed central minimum epithelial thickness (0.839; p < 0.001) but not BAD-D (0.972). Their AUCs rose from 0.666–0.677 in mild to 0.993–0.995 in severe keratoconus, a gradient that partly reflects the disease spectrum. For FFKC, the best epithelial AUC was 0.668 (6 mm epithelial thickness range) versus 0.728 for BAD-D, and adding five epithelial indices to tomography did not improve validated discrimination (out-of-bag AUC gain +0.000 for definite keratoconus and +0.012, 95% interval −0.080 to +0.083, for FFKC). Conclusions: CERI and CETR quantify epithelial remodeling and discriminate established keratoconus well, but they add little validated discrimination to Pentacam tomography; in FFKC, their discrimination was modest and any added value remains uncertain. They may complement, but not replace, tomography and biomechanics. 2026-11-13 Diagnostics, Vol. 16, Pages 3767: Beyond Epithelial Thickness: Comprehensive Profiling of Corneal Epithelial Remodeling and Its Diagnostic Value Across Keratoconus Severity: The Noor Multimodal Corneal Imaging Study (NMCIS)

Diagnostics doi: 10.3390/diagnostics16223767

Authors: Hassan Hashemi Mehrnaz Atighehchian Alireza Hashemi Mehdi Khabazkhoob

Background: Keratoconus causes characteristic spatial epithelial remodeling that may not be captured by conventional thickness measurements. Novel morphometric indices from MS-39 AS-OCT may better characterize these changes. Purpose: We aimed to evaluate novel MS-39 AS-OCT epithelial remodeling indices and compare their diagnostic accuracy with epithelial thickness and Pentacam tomography across the keratoconus spectrum, using an objective reference standard. Methods: This retrospective diagnostic accuracy study included 1319 eyes of 1286 patients with same-day Pentacam and MS-39 imaging at Noor Eye Hospital (2023–2025). Eyes were classified from the clinical records and Pentacam front-surface indices, without use of any epithelial data, as normal (n = 861), forme fruste keratoconus (FFKC; topographically normal fellow eye of very asymmetric ectasia; n = 40) or definite keratoconus (n = 418), graded mild, moderate or severe with the ABCD system. Generalized estimating equations, receiver operating characteristic (ROC) analysis with DeLong confidence intervals and cross-validated cut-offs, and bootstrap-validated logistic models were used. Results: The central epithelial remodeling index (CERI) and central epithelial thickness range (CETR) increased with severity (+0.137 and +6.13 µm per severity grade; both p < 0.001). For definite keratoconus, CERI (AUC 0.932; 95% CI 0.913–0.948) and CETR (0.930) outperformed central minimum epithelial thickness (0.839; p < 0.001) but not BAD-D (0.972). Their AUCs rose from 0.666–0.677 in mild to 0.993–0.995 in severe keratoconus, a gradient that partly reflects the disease spectrum. For FFKC, the best epithelial AUC was 0.668 (6 mm epithelial thickness range) versus 0.728 for BAD-D, and adding five epithelial indices to tomography did not improve validated discrimination (out-of-bag AUC gain +0.000 for definite keratoconus and +0.012, 95% interval −0.080 to +0.083, for FFKC). Conclusions: CERI and CETR quantify epithelial remodeling and discriminate established keratoconus well, but they add little validated discrimination to Pentacam tomography; in FFKC, their discrimination was modest and any added value remains uncertain. They may complement, but not replace, tomography and biomechanics.

]]> Beyond Epithelial Thickness: Comprehensive Profiling of Corneal Epithelial Remodeling and Its Diagnostic Value Across Keratoconus Severity: The Noor Multimodal Corneal Imaging Study (NMCIS) Hassan Hashemi Mehrnaz Atighehchian Alireza Hashemi Mehdi Khabazkhoob doi: 10.3390/diagnostics16223767 Diagnostics 2026-11-13 Diagnostics 2026-11-13 16 22 Article 3767 10.3390/diagnostics16223767 https://www.mdpi.com/2075-4418/16/22/3767 Diagnostics, Vol. 16, Pages 3766: Developmental Disabilities and Subsequent Asthma Diagnosis in Children: Diagnostic Implications from a Nationwide Population-Based Cohort Study https://www.mdpi.com/2075-4418/16/22/3766 Background: The longitudinal risk of asthma among children with developmental disabilities (DDs) remains unclear. This study evaluated the association between DD and subsequent asthma risk. Methods: We conducted a nationwide retrospective cohort study using Taiwan’s National Health Insurance Research Database from 2009 through 2019. Children younger than 18 years with a claims-based DD diagnosis were propensity-score-matched 1:1 with children without DD. Children with asthma before the index date were excluded. Incident recorded asthma was defined using ICD-9-CM code 493.- or ICD-10-CM code J45.-; ICD-10-CM J44.- was excluded. Cox proportional hazards models estimated adjusted hazard ratios (aHRs). Prespecified subtype analyses addressed DD heterogeneity. Results: The study included 213,759 children in each cohort. The DD cohort had 43,782 recorded asthma diagnoses during 1,503,077 person-years (29.13 per 1000 person-years), compared with 30,559 diagnoses during 1,620,645 person-years among controls (18.86 per 1000 person-years). DD was associated with a higher rate of subsequent recorded asthma diagnosis (aHR, 1.70; 95% CI, 1.67–1.72), with associations present in both sexes and all age strata. Subtype-specific aHRs ranged from 1.65 for developmental delay or speech and language disorders to 1.94 for autism spectrum disorder. Exploratory post-index therapy and medication estimates were not interpreted as causal treatment effects. Conclusions: In this administrative claims cohort, a pre-existing DD diagnosis was associated with an approximately 70% higher adjusted rate of a subsequent recorded asthma diagnosis. The finding may support careful respiratory assessment when symptoms occur. Prospective studies incorporating healthcare-utilization measures, standardized asthma confirmation, and objective pulmonary testing are needed. 2026-11-13 Diagnostics, Vol. 16, Pages 3766: Developmental Disabilities and Subsequent Asthma Diagnosis in Children: Diagnostic Implications from a Nationwide Population-Based Cohort Study

Diagnostics doi: 10.3390/diagnostics16223766

Authors: Jun-Jun Yeh Yung-Chi Cheng Yung-En Ko Yu-Wei Huang Liang-Kai Hsieh Yu-Han Huang Fuu-Jen Tsai Chia-Hung Kao

Background: The longitudinal risk of asthma among children with developmental disabilities (DDs) remains unclear. This study evaluated the association between DD and subsequent asthma risk. Methods: We conducted a nationwide retrospective cohort study using Taiwan’s National Health Insurance Research Database from 2009 through 2019. Children younger than 18 years with a claims-based DD diagnosis were propensity-score-matched 1:1 with children without DD. Children with asthma before the index date were excluded. Incident recorded asthma was defined using ICD-9-CM code 493.- or ICD-10-CM code J45.-; ICD-10-CM J44.- was excluded. Cox proportional hazards models estimated adjusted hazard ratios (aHRs). Prespecified subtype analyses addressed DD heterogeneity. Results: The study included 213,759 children in each cohort. The DD cohort had 43,782 recorded asthma diagnoses during 1,503,077 person-years (29.13 per 1000 person-years), compared with 30,559 diagnoses during 1,620,645 person-years among controls (18.86 per 1000 person-years). DD was associated with a higher rate of subsequent recorded asthma diagnosis (aHR, 1.70; 95% CI, 1.67–1.72), with associations present in both sexes and all age strata. Subtype-specific aHRs ranged from 1.65 for developmental delay or speech and language disorders to 1.94 for autism spectrum disorder. Exploratory post-index therapy and medication estimates were not interpreted as causal treatment effects. Conclusions: In this administrative claims cohort, a pre-existing DD diagnosis was associated with an approximately 70% higher adjusted rate of a subsequent recorded asthma diagnosis. The finding may support careful respiratory assessment when symptoms occur. Prospective studies incorporating healthcare-utilization measures, standardized asthma confirmation, and objective pulmonary testing are needed.

]]> Developmental Disabilities and Subsequent Asthma Diagnosis in Children: Diagnostic Implications from a Nationwide Population-Based Cohort Study Jun-Jun Yeh Yung-Chi Cheng Yung-En Ko Yu-Wei Huang Liang-Kai Hsieh Yu-Han Huang Fuu-Jen Tsai Chia-Hung Kao doi: 10.3390/diagnostics16223766 Diagnostics 2026-11-13 Diagnostics 2026-11-13 16 22 Article 3766 10.3390/diagnostics16223766 https://www.mdpi.com/2075-4418/16/22/3766 Diagnostics, Vol. 16, Pages 3765: FetalSANet: A Lightweight Spatial-Attention MobileNetV2 Framework for Fetal Ultrasound Plane Classification https://www.mdpi.com/2075-4418/16/22/3765 Reliable identification of standard fetal ultrasound planes underpins prenatal biometry and screening, but manual identification depends on the operator. This study evaluates FetalSANet, a lightweight MobileNetV2 classifier with a 98-parameter spatial-attention module, against channel-attention, dual-attention and no-attention variants on FETAL_PLANES_DB. On the released split (five classes, one seed), spatial attention reached 93.70% accuracy, but its difference from the no-attention baseline was not significant (McNemar p=0.429), and a perceptual-hash audit found near-duplicate images across the training, validation and test partitions, mainly in Fetal Thorax and Maternal Cervix. We therefore re-evaluated the baseline and FetalSANet on a patient-disjoint, deduplicated split (six classes) with three seeds: accuracy was 88.13±0.37% and 88.29±0.79%, with no significant difference in paired tests (not evidence of equivalence). The module adds 9.6 KFLOPs to a 0.60 GFLOP network. In an external-domain evaluation without fine-tuning (two classes, two sources, N=2588), unrestricted five-class accuracy was about 87% (96.64% when restricted to the two present classes), and 11.51% of predictions fell into absent classes; class and data source are confounded. Grad-CAM++ maps are qualitative examples only. Spatial attention is therefore a nearly free but not demonstrably beneficial addition, and released-split accuracy should not be read as patient-level performance. 2026-11-13 Diagnostics, Vol. 16, Pages 3765: FetalSANet: A Lightweight Spatial-Attention MobileNetV2 Framework for Fetal Ultrasound Plane Classification

Diagnostics doi: 10.3390/diagnostics16223765

Authors: Md Wahidur Rahman Md Rahat Khan Shakil Ahmed Haitham Y. Adarbah Mohammad Sadman Tahsin Afzel Noore

Reliable identification of standard fetal ultrasound planes underpins prenatal biometry and screening, but manual identification depends on the operator. This study evaluates FetalSANet, a lightweight MobileNetV2 classifier with a 98-parameter spatial-attention module, against channel-attention, dual-attention and no-attention variants on FETAL_PLANES_DB. On the released split (five classes, one seed), spatial attention reached 93.70% accuracy, but its difference from the no-attention baseline was not significant (McNemar p=0.429), and a perceptual-hash audit found near-duplicate images across the training, validation and test partitions, mainly in Fetal Thorax and Maternal Cervix. We therefore re-evaluated the baseline and FetalSANet on a patient-disjoint, deduplicated split (six classes) with three seeds: accuracy was 88.13±0.37% and 88.29±0.79%, with no significant difference in paired tests (not evidence of equivalence). The module adds 9.6 KFLOPs to a 0.60 GFLOP network. In an external-domain evaluation without fine-tuning (two classes, two sources, N=2588), unrestricted five-class accuracy was about 87% (96.64% when restricted to the two present classes), and 11.51% of predictions fell into absent classes; class and data source are confounded. Grad-CAM++ maps are qualitative examples only. Spatial attention is therefore a nearly free but not demonstrably beneficial addition, and released-split accuracy should not be read as patient-level performance.

]]> FetalSANet: A Lightweight Spatial-Attention MobileNetV2 Framework for Fetal Ultrasound Plane Classification Md Wahidur Rahman Md Rahat Khan Shakil Ahmed Haitham Y. Adarbah Mohammad Sadman Tahsin Afzel Noore doi: 10.3390/diagnostics16223765 Diagnostics 2026-11-13 Diagnostics 2026-11-13 16 22 Article 3765 10.3390/diagnostics16223765 https://www.mdpi.com/2075-4418/16/22/3765 Diagnostics, Vol. 16, Pages 3764: Cancer Therapy-Induced Right Ventricular Systolic and Diastolic Dysfunction Assessed Using Conventional Echocardiographic Indices: A Prospective Observational Study https://www.mdpi.com/2075-4418/16/22/3764 Background/Objectives: Cancer treatment can impair right ventricular (RV) systolic and diastolic function by altering cardiomyocyte metabolism and inducing cell death. The incidence and prognosis of cancer therapy-induced RV involvement remain uncertain. We assessed RV diastolic changes and their association with systolic RV and LV dysfunction in cancer patients. Methods: We prospectively observed 60 adults (91.7% female, aged 31 to 74 years) with breast or gastrointestinal cancer receiving chemotherapy for a median of 381 days (IQR 187, 464), excluding those with cardiovascular or pulmonary disease. RV diastolic function was assessed using the 2010 right heart echocardiographic guidelines. RV systolic dysfunction was defined by abnormal values in at least two of the following RV indices: fractional area change (RVFAC), systolic tissue Doppler velocity (RVS’), tricuspid annular plane systolic excursion, or myocardial performance index. LV dysfunction was defined by abnormal LV ejection fraction or average systolic LV tissue Doppler velocity. Results: RV systolic dysfunction was found in 7 patients (11.7%), RV diastolic dysfunction in 12 (30.7%), and LV dysfunction in 11 (18.3%). Generalised estimating equations showed early decreases in RVS’ and RVFAC at the first month (β = −0.68, p = 0.016; β = −2.2, p = 0.006), and later changes in RV early diastolic tissue velocity (RVe′) and the ratio of early RV filling velocity (RVE) to RVe′ (RVE/e′) at the third month (β = −1.03, p = 0.005; β = 0.35, p = 0.034). Higher RVFAC values were linked to lower odds of LV dysfunction (OR 0.88, p = 0.002). RVe′ was associated with RV systolic dysfunction (OR 0.61, p < 0.001), with a threshold of 10 cm/s (AUC 0.81; 95% CI: 0.69, 0.93). Conclusions: Conventional echocardiographic parameters may facilitate the detection of RV systolic and diastolic dysfunction during cancer therapy. Early alterations and the prognostic value of RV parameters support the necessity for their routine monitoring. 2026-11-13 Diagnostics, Vol. 16, Pages 3764: Cancer Therapy-Induced Right Ventricular Systolic and Diastolic Dysfunction Assessed Using Conventional Echocardiographic Indices: A Prospective Observational Study

Diagnostics doi: 10.3390/diagnostics16223764

Authors: Svetoslava Elefterova Slavcheva Nikolay Conev Atanas Angelov

Background/Objectives: Cancer treatment can impair right ventricular (RV) systolic and diastolic function by altering cardiomyocyte metabolism and inducing cell death. The incidence and prognosis of cancer therapy-induced RV involvement remain uncertain. We assessed RV diastolic changes and their association with systolic RV and LV dysfunction in cancer patients. Methods: We prospectively observed 60 adults (91.7% female, aged 31 to 74 years) with breast or gastrointestinal cancer receiving chemotherapy for a median of 381 days (IQR 187, 464), excluding those with cardiovascular or pulmonary disease. RV diastolic function was assessed using the 2010 right heart echocardiographic guidelines. RV systolic dysfunction was defined by abnormal values in at least two of the following RV indices: fractional area change (RVFAC), systolic tissue Doppler velocity (RVS’), tricuspid annular plane systolic excursion, or myocardial performance index. LV dysfunction was defined by abnormal LV ejection fraction or average systolic LV tissue Doppler velocity. Results: RV systolic dysfunction was found in 7 patients (11.7%), RV diastolic dysfunction in 12 (30.7%), and LV dysfunction in 11 (18.3%). Generalised estimating equations showed early decreases in RVS’ and RVFAC at the first month (β = −0.68, p = 0.016; β = −2.2, p = 0.006), and later changes in RV early diastolic tissue velocity (RVe′) and the ratio of early RV filling velocity (RVE) to RVe′ (RVE/e′) at the third month (β = −1.03, p = 0.005; β = 0.35, p = 0.034). Higher RVFAC values were linked to lower odds of LV dysfunction (OR 0.88, p = 0.002). RVe′ was associated with RV systolic dysfunction (OR 0.61, p < 0.001), with a threshold of 10 cm/s (AUC 0.81; 95% CI: 0.69, 0.93). Conclusions: Conventional echocardiographic parameters may facilitate the detection of RV systolic and diastolic dysfunction during cancer therapy. Early alterations and the prognostic value of RV parameters support the necessity for their routine monitoring.

]]> Cancer Therapy-Induced Right Ventricular Systolic and Diastolic Dysfunction Assessed Using Conventional Echocardiographic Indices: A Prospective Observational Study Svetoslava Elefterova Slavcheva Nikolay Conev Atanas Angelov doi: 10.3390/diagnostics16223764 Diagnostics 2026-11-13 Diagnostics 2026-11-13 16 22 Article 3764 10.3390/diagnostics16223764 https://www.mdpi.com/2075-4418/16/22/3764 Diagnostics, Vol. 16, Pages 3763: Microbiological Assessment of Halitosis in Users of E-Cigarettes, Heated Tobacco Products, and Combustible Cigarettes https://www.mdpi.com/2075-4418/16/22/3763 Background/Objectives: The diagnostic value of oral microbiological testing in users of different nicotine products remains uncertain. We compared tongue-coating dysbiosis, salivary cultures, and chairside enzymatic activity across product groups and evaluated their discrimination of objective halitosis. Methods: This cross-sectional study included 225 adults: 60 never-users, 55 combustible cigarette users, 52 heated tobacco product users, and 58 e-cigarette users. Six tongue-coating taxa and total bacterial load were quantified by quantitative polymerase chain reaction. Salivary cultures and the benzoyl-DL-arginine-naphthylamide (BANA) test complemented organoleptic assessment and volatile sulfur compound measurement. Analyses included adjusted regression, compositional analysis, exploratory profiling and mediation, and receiver operating characteristic analysis. Results: Adjusted dysbiosis-index differences versus never-users were 1.82, 1.50, and 2.08 units for combustible cigarette, heated tobacco product, and e-cigarette users, respectively (all p < 0.001). E-cigarette users had the highest Solobacterium moorei load and Candida carriage, whereas combustible cigarette users had the highest Porphyromonas gingivalis load and BANA positivity. Permutational multivariate analysis of variance (PERMANOVA) R2 was 15.8%, with heterogeneous dispersions. Objective halitosis prevalence ranged from 10.8% to 66.7% across microbial profiles. The chairside/culture panel and dysbiosis index had areas under the curve of 0.72 and 0.71, respectively. Conclusions: Microbial differences were associated with product use, but exposure history and oral conditions may confound these associations. Moderate discrimination and absent external validation preclude diagnostic interchangeability or routine implementation of these adjunctive tests. 2026-11-13 Diagnostics, Vol. 16, Pages 3763: Microbiological Assessment of Halitosis in Users of E-Cigarettes, Heated Tobacco Products, and Combustible Cigarettes

Diagnostics doi: 10.3390/diagnostics16223763

Authors: Romina Georgiana Bita Mihail Pantor Mihai Benchea Edida Maghet Livia Stanga Adrian Nicoara

Background/Objectives: The diagnostic value of oral microbiological testing in users of different nicotine products remains uncertain. We compared tongue-coating dysbiosis, salivary cultures, and chairside enzymatic activity across product groups and evaluated their discrimination of objective halitosis. Methods: This cross-sectional study included 225 adults: 60 never-users, 55 combustible cigarette users, 52 heated tobacco product users, and 58 e-cigarette users. Six tongue-coating taxa and total bacterial load were quantified by quantitative polymerase chain reaction. Salivary cultures and the benzoyl-DL-arginine-naphthylamide (BANA) test complemented organoleptic assessment and volatile sulfur compound measurement. Analyses included adjusted regression, compositional analysis, exploratory profiling and mediation, and receiver operating characteristic analysis. Results: Adjusted dysbiosis-index differences versus never-users were 1.82, 1.50, and 2.08 units for combustible cigarette, heated tobacco product, and e-cigarette users, respectively (all p < 0.001). E-cigarette users had the highest Solobacterium moorei load and Candida carriage, whereas combustible cigarette users had the highest Porphyromonas gingivalis load and BANA positivity. Permutational multivariate analysis of variance (PERMANOVA) R2 was 15.8%, with heterogeneous dispersions. Objective halitosis prevalence ranged from 10.8% to 66.7% across microbial profiles. The chairside/culture panel and dysbiosis index had areas under the curve of 0.72 and 0.71, respectively. Conclusions: Microbial differences were associated with product use, but exposure history and oral conditions may confound these associations. Moderate discrimination and absent external validation preclude diagnostic interchangeability or routine implementation of these adjunctive tests.

]]> Microbiological Assessment of Halitosis in Users of E-Cigarettes, Heated Tobacco Products, and Combustible Cigarettes Romina Georgiana Bita Mihail Pantor Mihai Benchea Edida Maghet Livia Stanga Adrian Nicoara doi: 10.3390/diagnostics16223763 Diagnostics 2026-11-13 Diagnostics 2026-11-13 16 22 Article 3763 10.3390/diagnostics16223763 https://www.mdpi.com/2075-4418/16/22/3763 Diagnostics, Vol. 16, Pages 3762: LQ-HybridNet: A Parameter-Compact Classical Architecture with Quantum-Inspired Feature Transformations for Skin Lesion Classification https://www.mdpi.com/2075-4418/16/22/3762 Background/Objectives: This study evaluates LQ-HybridNet, a parameter-compact classical architecture for skin-lesion classification. Methods: MobileNetV2 is augmented with amplitude–phase channel gating and a four-qubit variational circuit feature transformation. Crucially, all evaluations enforce a rigorous, leakage-resistant stratified lesion-level split to prevent data contamination. Here, quantum-inspired denotes a classical mathematical inductive bias, not quantum hardware execution or computational advantage. Results: On HAM10000, LQ-HybridNet achieved 90.80±0.25% accuracy, 0.7714 macro precision, 0.7257 macro recall, and 0.7428 macro F1-score, compared with 88.50±0.30% accuracy for MobileNetV2. The 2.30 percentage-point gain required 45.9K additional parameters. Across the evaluated backbones, accuracy gains ranged from 1.10 to 2.40 percentage points on HAM10000 and 1.77 to 4.00 points on ISIC 2018. Latency increased from 12.4 to 48.7 ms per batch of 32 images. Conclusions: The structured classical transformations yielded incremental benchmark improvements with small parameter overhead but approximately 3.9-fold higher latency. These results concern the evaluated architectures and benchmark distributions; parameter compactness does not imply inference efficiency. 2026-11-13 Diagnostics, Vol. 16, Pages 3762: LQ-HybridNet: A Parameter-Compact Classical Architecture with Quantum-Inspired Feature Transformations for Skin Lesion Classification

Diagnostics doi: 10.3390/diagnostics16223762

Authors: Prateek Singh Sudhakar Singh Manoj Kumar Jena Venkata Pramod Nutheti Pavan Kumar Vunnava Masabattula Naga Siva Sai Durgamba

Background/Objectives: This study evaluates LQ-HybridNet, a parameter-compact classical architecture for skin-lesion classification. Methods: MobileNetV2 is augmented with amplitude–phase channel gating and a four-qubit variational circuit feature transformation. Crucially, all evaluations enforce a rigorous, leakage-resistant stratified lesion-level split to prevent data contamination. Here, quantum-inspired denotes a classical mathematical inductive bias, not quantum hardware execution or computational advantage. Results: On HAM10000, LQ-HybridNet achieved 90.80±0.25% accuracy, 0.7714 macro precision, 0.7257 macro recall, and 0.7428 macro F1-score, compared with 88.50±0.30% accuracy for MobileNetV2. The 2.30 percentage-point gain required 45.9K additional parameters. Across the evaluated backbones, accuracy gains ranged from 1.10 to 2.40 percentage points on HAM10000 and 1.77 to 4.00 points on ISIC 2018. Latency increased from 12.4 to 48.7 ms per batch of 32 images. Conclusions: The structured classical transformations yielded incremental benchmark improvements with small parameter overhead but approximately 3.9-fold higher latency. These results concern the evaluated architectures and benchmark distributions; parameter compactness does not imply inference efficiency.

]]> LQ-HybridNet: A Parameter-Compact Classical Architecture with Quantum-Inspired Feature Transformations for Skin Lesion Classification Prateek Singh Sudhakar Singh Manoj Kumar Jena Venkata Pramod Nutheti Pavan Kumar Vunnava Masabattula Naga Siva Sai Durgamba doi: 10.3390/diagnostics16223762 Diagnostics 2026-11-13 Diagnostics 2026-11-13 16 22 Article 3762 10.3390/diagnostics16223762 https://www.mdpi.com/2075-4418/16/22/3762 Diagnostics, Vol. 16, Pages 3761: Which Definition Is the Gold Standard? Reference-Standard Choice and the Reported Accuracy of Periprosthetic Joint Infection Diagnostic Tests: A Meta-Epidemiological Systematic Review https://www.mdpi.com/2075-4418/16/22/3761 Background/Objectives: Periprosthetic joint infection (PJI) has no gold standard. Accuracy studies borrow one of several composite definitions instead, and these definitions do not label the same patients as infected. We asked how often accuracy studies say which definition they used, and how far the choice moves the numbers they report. Methods: In this systematic review, we searched PubMed on 20 October 2026 for primary accuracy studies of PJI tests and classified each abstract by the reference definition it named. Studies that applied two or more definitions (MSIS 2011/2013, ICM 2018, IDSA 2013, EBJIS proposed or 2021) to the same cohort were assessed further, and accuracy was extracted per definition. Ratios of PJI cases and the change in sensitivity of the alpha-defensin test were pooled with random-effects models. Results: Of 1744 accuracy studies, 437 (25%) named a reference definition in the abstract. The share rose from none before 2012 to 35% from 2021 onward. Seventeen studies reported accuracy under more than one definition in the same patients. EBJIS classified 1.47 times as many patients as infected as MSIS (95% CI 1.33–1.62; 6 cohorts; I2 = 4%) and 1.26 times as many as ICM 2018 (1.08–1.46; 6 cohorts; I2 = 58%). The pooled sensitivity of the alpha-defensin test was 85.6% (76.9–91.4) against MSIS and 56.3% (48.6–63.7) against EBJIS in the same three cohorts, while specificity stayed between 89% and 100%. Across 13 test–cohort pairs, the median change in sensitivity when the reference moved to EBJIS was −18.5 percentage points (IQR −29.0 to −4.9); sensitivity fell in 10 pairs and changed by less than 3 points in three. Conclusions: For several PJI tests, the reported sensitivity depends substantially on the reference definition chosen. A definition that labels more patients as infected is not, for that reason, a more accurate one. Accuracy figures obtained under different definitions should not be pooled or compared as if they measured the same thing, and every accuracy study should name its reference definition in the abstract. 2026-11-13 Diagnostics, Vol. 16, Pages 3761: Which Definition Is the Gold Standard? Reference-Standard Choice and the Reported Accuracy of Periprosthetic Joint Infection Diagnostic Tests: A Meta-Epidemiological Systematic Review

Diagnostics doi: 10.3390/diagnostics16223761

Authors: Vensan Velchov Alexander Slavov Georgi Lukanov

Background/Objectives: Periprosthetic joint infection (PJI) has no gold standard. Accuracy studies borrow one of several composite definitions instead, and these definitions do not label the same patients as infected. We asked how often accuracy studies say which definition they used, and how far the choice moves the numbers they report. Methods: In this systematic review, we searched PubMed on 20 October 2026 for primary accuracy studies of PJI tests and classified each abstract by the reference definition it named. Studies that applied two or more definitions (MSIS 2011/2013, ICM 2018, IDSA 2013, EBJIS proposed or 2021) to the same cohort were assessed further, and accuracy was extracted per definition. Ratios of PJI cases and the change in sensitivity of the alpha-defensin test were pooled with random-effects models. Results: Of 1744 accuracy studies, 437 (25%) named a reference definition in the abstract. The share rose from none before 2012 to 35% from 2021 onward. Seventeen studies reported accuracy under more than one definition in the same patients. EBJIS classified 1.47 times as many patients as infected as MSIS (95% CI 1.33–1.62; 6 cohorts; I2 = 4%) and 1.26 times as many as ICM 2018 (1.08–1.46; 6 cohorts; I2 = 58%). The pooled sensitivity of the alpha-defensin test was 85.6% (76.9–91.4) against MSIS and 56.3% (48.6–63.7) against EBJIS in the same three cohorts, while specificity stayed between 89% and 100%. Across 13 test–cohort pairs, the median change in sensitivity when the reference moved to EBJIS was −18.5 percentage points (IQR −29.0 to −4.9); sensitivity fell in 10 pairs and changed by less than 3 points in three. Conclusions: For several PJI tests, the reported sensitivity depends substantially on the reference definition chosen. A definition that labels more patients as infected is not, for that reason, a more accurate one. Accuracy figures obtained under different definitions should not be pooled or compared as if they measured the same thing, and every accuracy study should name its reference definition in the abstract.

]]> Which Definition Is the Gold Standard? Reference-Standard Choice and the Reported Accuracy of Periprosthetic Joint Infection Diagnostic Tests: A Meta-Epidemiological Systematic Review Vensan Velchov Alexander Slavov Georgi Lukanov doi: 10.3390/diagnostics16223761 Diagnostics 2026-11-13 Diagnostics 2026-11-13 16 22 Systematic Review 3761 10.3390/diagnostics16223761 https://www.mdpi.com/2075-4418/16/22/3761 Diagnostics, Vol. 16, Pages 3760: Synthetic Haematocrit for Myocardial Extracellular Volume Mapping in Clinical Practice at 1.5 T and 3 T https://www.mdpi.com/2075-4418/16/22/3760 Background/Objectives: Synthetic haematocrit (HCT) permits cardiovascular magnetic resonance (CMR) extracellular volume fraction (ECV) estimation without contemporaneous laboratory HCT. We evaluated four published equations in a clinical referral cohort. Methods: This retrospective audit included 67 adults scanned at 1.5 T (n = 34) or 3 T (n = 33), with laboratory HCT within 24 h. Two equations per field strength were assessed using correlation and Bland–Altman analysis with confidence intervals. Observer reproducibility of T1 and calculated synthetic ECV was assessed using intraclass correlation coefficients (ICCs). Post hoc exploratory analyses examined classification at ECV ≥ 30%, estimation-error associations and proportional bias. Results: Absolute mean ECV bias was below one percentage point for all equations, but model-specific limits of agreement extended from −4.47 to 4.19 percentage points. At the exploratory 30% threshold, classification agreement was 85.3% and 88.2% at 1.5 T and 75.8% for both equations at 3 T. Synthetic ECV intraobserver ICCs ranged from 0.853 to 0.949; interobserver ICCs were 0.936–0.944 at 1.5 T and 0.842–0.851 at 3 T. Shang HCT showed magnitude-dependent disagreement. Conclusions: Synthetic ECV may help assess myocardial tissue when timely laboratory haematocrit is unavailable, with low average differences from conventional ECV. However, the small groups limit precision and generalisability, and individual and observer differences prevent assuming interchangeability. Local validation is needed before using synthetic ECV for clinical decisions or monitoring changes over time. 2026-11-13 Diagnostics, Vol. 16, Pages 3760: Synthetic Haematocrit for Myocardial Extracellular Volume Mapping in Clinical Practice at 1.5 T and 3 T

Diagnostics doi: 10.3390/diagnostics16223760

Authors: Elif Ayduk Gövdeli Mohamed Elzoghby Teresa Maria Capovilla Daniele Muser Gianfranco Sinagra Gaetano Nucifora

Background/Objectives: Synthetic haematocrit (HCT) permits cardiovascular magnetic resonance (CMR) extracellular volume fraction (ECV) estimation without contemporaneous laboratory HCT. We evaluated four published equations in a clinical referral cohort. Methods: This retrospective audit included 67 adults scanned at 1.5 T (n = 34) or 3 T (n = 33), with laboratory HCT within 24 h. Two equations per field strength were assessed using correlation and Bland–Altman analysis with confidence intervals. Observer reproducibility of T1 and calculated synthetic ECV was assessed using intraclass correlation coefficients (ICCs). Post hoc exploratory analyses examined classification at ECV ≥ 30%, estimation-error associations and proportional bias. Results: Absolute mean ECV bias was below one percentage point for all equations, but model-specific limits of agreement extended from −4.47 to 4.19 percentage points. At the exploratory 30% threshold, classification agreement was 85.3% and 88.2% at 1.5 T and 75.8% for both equations at 3 T. Synthetic ECV intraobserver ICCs ranged from 0.853 to 0.949; interobserver ICCs were 0.936–0.944 at 1.5 T and 0.842–0.851 at 3 T. Shang HCT showed magnitude-dependent disagreement. Conclusions: Synthetic ECV may help assess myocardial tissue when timely laboratory haematocrit is unavailable, with low average differences from conventional ECV. However, the small groups limit precision and generalisability, and individual and observer differences prevent assuming interchangeability. Local validation is needed before using synthetic ECV for clinical decisions or monitoring changes over time.

]]> Synthetic Haematocrit for Myocardial Extracellular Volume Mapping in Clinical Practice at 1.5 T and 3 T Elif Ayduk Gövdeli Mohamed Elzoghby Teresa Maria Capovilla Daniele Muser Gianfranco Sinagra Gaetano Nucifora doi: 10.3390/diagnostics16223760 Diagnostics 2026-11-13 Diagnostics 2026-11-13 16 22 Article 3760 10.3390/diagnostics16223760 https://www.mdpi.com/2075-4418/16/22/3760 Diagnostics, Vol. 16, Pages 3759: Integrated Urinary Metabolomics and Artificial Intelligence for the Identification of Diagnostic, Prognostic, and Progression Biomarkers in Chronic Kidney Disease https://www.mdpi.com/2075-4418/16/22/3759 Background: Chronic kidney disease (CKD) affects approximately 10% of the global population, and it is a critical challenge for public health worldwide. The integration of metabolomics with machine learning (ML) has emerged as a promising approach to enhancing disease diagnosis and prognosis. Objective: This study characterized the urinary metabolomic profiles of individuals with intermediate-to-advanced CKD and developed predictive models for disease diagnosis and prognosis. Methods: Urine samples from 129 participants, including healthy individuals and patients with CKD, were analyzed using liquid chromatography tandem mass spectrometry (LC-MS/MS). Multivariate analysis was performed to identify differences between groups. ML algorithms were the best for developing predictive models for the diagnosis, prognosis, and progression of CKD. Results: The results show the identities of 1499 metabolites. They also indicate that ML models effectively differentiated between healthy individuals and CKD patients, demonstrating high accuracy and specificity. The RF model was effective for diagnostic purposes, while the SVM showed superior performance in prognostic and disease progression predictions. The differentially expressed metabolites found, predominantly lipids, may serve as potential biomarkers for the detection and progression of CKD. Conclusions: The combination of urinary metabolomics with ML algorithms represents a promising, non-invasive approach for CKD diagnosis and follow-up, offering an alternative that may improve both the precision and personalization of disease management. 2026-11-13 Diagnostics, Vol. 16, Pages 3759: Integrated Urinary Metabolomics and Artificial Intelligence for the Identification of Diagnostic, Prognostic, and Progression Biomarkers in Chronic Kidney Disease

Diagnostics doi: 10.3390/diagnostics16223759

Authors: Bianca Uliana Picolo Letícia Cristina Machado de Sousa Nathalia Rabello Silva Ana Luiza Barbosa Ferreira Michelly Yorrana Miranda de Araujo Ana Laura Fonseca Orlandi Mario Machado Martins Hebréia Oliveira Almeida-Souza Tiara da Costa Silva Marcus Vinícius de Pádua Netto Luiz Ricardo Goulart Filho Vivian Alonso-Goulart Luciana Saraiva da Silva

Background: Chronic kidney disease (CKD) affects approximately 10% of the global population, and it is a critical challenge for public health worldwide. The integration of metabolomics with machine learning (ML) has emerged as a promising approach to enhancing disease diagnosis and prognosis. Objective: This study characterized the urinary metabolomic profiles of individuals with intermediate-to-advanced CKD and developed predictive models for disease diagnosis and prognosis. Methods: Urine samples from 129 participants, including healthy individuals and patients with CKD, were analyzed using liquid chromatography tandem mass spectrometry (LC-MS/MS). Multivariate analysis was performed to identify differences between groups. ML algorithms were the best for developing predictive models for the diagnosis, prognosis, and progression of CKD. Results: The results show the identities of 1499 metabolites. They also indicate that ML models effectively differentiated between healthy individuals and CKD patients, demonstrating high accuracy and specificity. The RF model was effective for diagnostic purposes, while the SVM showed superior performance in prognostic and disease progression predictions. The differentially expressed metabolites found, predominantly lipids, may serve as potential biomarkers for the detection and progression of CKD. Conclusions: The combination of urinary metabolomics with ML algorithms represents a promising, non-invasive approach for CKD diagnosis and follow-up, offering an alternative that may improve both the precision and personalization of disease management.

]]> Integrated Urinary Metabolomics and Artificial Intelligence for the Identification of Diagnostic, Prognostic, and Progression Biomarkers in Chronic Kidney Disease Bianca Uliana Picolo Letícia Cristina Machado de Sousa Nathalia Rabello Silva Ana Luiza Barbosa Ferreira Michelly Yorrana Miranda de Araujo Ana Laura Fonseca Orlandi Mario Machado Martins Hebréia Oliveira Almeida-Souza Tiara da Costa Silva Marcus Vinícius de Pádua Netto Luiz Ricardo Goulart Filho Vivian Alonso-Goulart Luciana Saraiva da Silva doi: 10.3390/diagnostics16223759 Diagnostics 2026-11-13 Diagnostics 2026-11-13 16 22 Article 3759 10.3390/diagnostics16223759 https://www.mdpi.com/2075-4418/16/22/3759 Diagnostics, Vol. 16, Pages 3758: Uncertainty and Geometric Image-Region Ranking in Artificial Intelligence-Based Panoramic Tooth Segmentation: A Multi-Source External Benchmark https://www.mdpi.com/2075-4418/16/22/3758 Background/Objectives: This retrospective benchmark evaluated scores for selecting regions of panoramic tooth segmentations for review. Methods: Three-member U-Net ensembles trained on UFBA-425 were evaluated on 590 held-out images and subsequently on 329 photographed radiographs. The original mixed-granularity pipeline comparison used the calibrated residual ensemble on 100 pediatric images. Cells in a 2 × 4 grid received regional mutual information (MI) scores but shared one whole-image soft Dice confidence (SDC) value. A lower Dice-risk area under the risk–coverage curve (AURC) indicated better ranking against source masks. Interaction tests, quality subset analyses, and prediction-positive sensitivity analyses were post hoc. Image-key bootstrap intervals may be too narrow for patient-level inference because patient independence was unverified. Results: The primary MI-minus-SDC AURC difference was +0.007 (95% confidence interval −0.033 to +0.041), leaving the comparison inconclusive. Subsequent evaluations were exploratory. Analyses of reference-positive cells (containing reference tooth pixels) received co-principal emphasis after outcomes were known. MI had a higher Dice-risk AURC than the replicated SDC in the pediatric main subset (+0.238) and the local SDC in AKUDENTAL (+0.157 residual, +0.134 ResNet18). When 20% of grid cells were reviewed, the mean maximum pixel probability (MSP) captured more error pixels than MI in seven of ten source/model comparisons, including both AKUDENTAL ensembles. On photographed radiographs, the MSP led by 15.73 percentage points for the residual ensemble and MI by 3.66 for ResNet18. For ResNet18, equal weighting of false-positive and false-negative capture favored MSP by 6.59 points. Conclusions: The primary comparison established neither superiority nor equivalence. Exploratory capture varied by source, model, and error mix. 2026-11-12 Diagnostics, Vol. 16, Pages 3758: Uncertainty and Geometric Image-Region Ranking in Artificial Intelligence-Based Panoramic Tooth Segmentation: A Multi-Source External Benchmark

Diagnostics doi: 10.3390/diagnostics16223758

Authors: Yelda Fırat

Background/Objectives: This retrospective benchmark evaluated scores for selecting regions of panoramic tooth segmentations for review. Methods: Three-member U-Net ensembles trained on UFBA-425 were evaluated on 590 held-out images and subsequently on 329 photographed radiographs. The original mixed-granularity pipeline comparison used the calibrated residual ensemble on 100 pediatric images. Cells in a 2 × 4 grid received regional mutual information (MI) scores but shared one whole-image soft Dice confidence (SDC) value. A lower Dice-risk area under the risk–coverage curve (AURC) indicated better ranking against source masks. Interaction tests, quality subset analyses, and prediction-positive sensitivity analyses were post hoc. Image-key bootstrap intervals may be too narrow for patient-level inference because patient independence was unverified. Results: The primary MI-minus-SDC AURC difference was +0.007 (95% confidence interval −0.033 to +0.041), leaving the comparison inconclusive. Subsequent evaluations were exploratory. Analyses of reference-positive cells (containing reference tooth pixels) received co-principal emphasis after outcomes were known. MI had a higher Dice-risk AURC than the replicated SDC in the pediatric main subset (+0.238) and the local SDC in AKUDENTAL (+0.157 residual, +0.134 ResNet18). When 20% of grid cells were reviewed, the mean maximum pixel probability (MSP) captured more error pixels than MI in seven of ten source/model comparisons, including both AKUDENTAL ensembles. On photographed radiographs, the MSP led by 15.73 percentage points for the residual ensemble and MI by 3.66 for ResNet18. For ResNet18, equal weighting of false-positive and false-negative capture favored MSP by 6.59 points. Conclusions: The primary comparison established neither superiority nor equivalence. Exploratory capture varied by source, model, and error mix.

]]> Uncertainty and Geometric Image-Region Ranking in Artificial Intelligence-Based Panoramic Tooth Segmentation: A Multi-Source External Benchmark Yelda Fırat doi: 10.3390/diagnostics16223758 Diagnostics 2026-11-12 Diagnostics 2026-11-12 16 22 Article 3758 10.3390/diagnostics16223758 https://www.mdpi.com/2075-4418/16/22/3758 Diagnostics, Vol. 16, Pages 3757: Super-Resolution Ultrasound Microvascular Features in Breast Invasive Ductal Carcinoma: Associations with Ki-67 Status and Stromal Tumor-Infiltrating Lymphocyte Categories https://www.mdpi.com/2075-4418/16/22/3757 Background/Objectives: Super-resolution ultrasound (SRUS) depicts tumor microvascular structure and flow. We examined associations with Ki-67 status, stromal tumor-infiltrating lymphocyte (sTIL) categories, and immunohistochemistry-based surrogate subtypes in untreated breast invasive ductal carcinoma (IDC). Methods: This single-center retrospective secondary analysis included 72 surgically confirmed IDCs. Ki-67 was categorized as low (<20%; n = 31) or high (≥20%; n = 41) and sTILs as three ordered categories. Eight SRUS fields underwent endpoint-specific false-discovery-rate correction. Revision-stage logistic and ordinal logistic models examined four selected features separately, adjusting for age and log-transformed lesion volume. Results: Complexity levels and vessel ratios were higher in high-Ki-67 tumors (both q < 0.001). Maximum curvature based on the sum-of-angles metric (MaxCurvatureSOAM) and density entropy (DenEntropy) were inversely associated with the sTIL category (Spearman ρ = −0.475 and −0.411; both q < 0.001). These four association directions persisted after age/volume adjustment (all q < 0.001), although Ki-67 effect estimates were imprecise and sensitive to individual observations. Subtype differences were exploratory, with the two smallest groups containing nine and six tumors. A supplementary two-feature analysis did not establish incremental clinical value over the vessel ratio alone. Conclusions: SRUS features showed exploratory imaging–pathology associations that persisted after limited clinical adjustment. Residual confounding, small subtype groups, platform-specific measurements, and the absence of external validation preclude claims of independent biological effects or clinical decision utility. 2026-11-12 Diagnostics, Vol. 16, Pages 3757: Super-Resolution Ultrasound Microvascular Features in Breast Invasive Ductal Carcinoma: Associations with Ki-67 Status and Stromal Tumor-Infiltrating Lymphocyte Categories

Diagnostics doi: 10.3390/diagnostics16223757

Authors: Yanshuo Shi Zhaolin Yin Anna Xu Xiaohui Ji Yueheng Wang

Background/Objectives: Super-resolution ultrasound (SRUS) depicts tumor microvascular structure and flow. We examined associations with Ki-67 status, stromal tumor-infiltrating lymphocyte (sTIL) categories, and immunohistochemistry-based surrogate subtypes in untreated breast invasive ductal carcinoma (IDC). Methods: This single-center retrospective secondary analysis included 72 surgically confirmed IDCs. Ki-67 was categorized as low (<20%; n = 31) or high (≥20%; n = 41) and sTILs as three ordered categories. Eight SRUS fields underwent endpoint-specific false-discovery-rate correction. Revision-stage logistic and ordinal logistic models examined four selected features separately, adjusting for age and log-transformed lesion volume. Results: Complexity levels and vessel ratios were higher in high-Ki-67 tumors (both q < 0.001). Maximum curvature based on the sum-of-angles metric (MaxCurvatureSOAM) and density entropy (DenEntropy) were inversely associated with the sTIL category (Spearman ρ = −0.475 and −0.411; both q < 0.001). These four association directions persisted after age/volume adjustment (all q < 0.001), although Ki-67 effect estimates were imprecise and sensitive to individual observations. Subtype differences were exploratory, with the two smallest groups containing nine and six tumors. A supplementary two-feature analysis did not establish incremental clinical value over the vessel ratio alone. Conclusions: SRUS features showed exploratory imaging–pathology associations that persisted after limited clinical adjustment. Residual confounding, small subtype groups, platform-specific measurements, and the absence of external validation preclude claims of independent biological effects or clinical decision utility.

]]> Super-Resolution Ultrasound Microvascular Features in Breast Invasive Ductal Carcinoma: Associations with Ki-67 Status and Stromal Tumor-Infiltrating Lymphocyte Categories Yanshuo Shi Zhaolin Yin Anna Xu Xiaohui Ji Yueheng Wang doi: 10.3390/diagnostics16223757 Diagnostics 2026-11-12 Diagnostics 2026-11-12 16 22 Article 3757 10.3390/diagnostics16223757 https://www.mdpi.com/2075-4418/16/22/3757 Diagnostics, Vol. 16, Pages 3754: Robustness of U-Net Retinal Layer Segmentation to Controlled OCT Image Degradation https://www.mdpi.com/2075-4418/16/22/3754 Background: Optical coherence tomography (OCT) retinal layer segmentation supports quantitative clinical assessment, but its robustness to different image degradation has not been systematically characterized. Methods: This study evaluates a U-Net trained on unmodified OCT5k scans under seven synthetic degradation families at five family-specific severity levels. The test set included 315 held-out B-scans from nine cases, with three cases each of age-related macular degeneration, diabetic macular edema, and healthy retinas. After ordered boundary decoding, two primary outcomes were calculated: boundary mean absolute error (MAE, pixels) and internal-layer Dice. Results: Clean images yielded macro-MAE of 3.66 pixels and macro-Dice of 0.934. At severity 5, MAE increased in five families and Dice decreased in all seven. Gaussian noise, contrast reduction, and global attenuation produced the largest deterioration, with macro-MAE/macro-Dice values of 94.35/0.715, 236.81/0.044, and 112.32/0.0004, respectively. Adjusted paired tests showed statistically significant deterioration in both outcomes for these three families; macro-Dice also showed declines under defocus, shadowing, and axial-resolution reduction, while speckle showed no significant change. Conclusions: These results indicate corruption- and metric-specific vulnerability in the tested U-Net. This study may inform the development of automated OCT image-quality screening. Before clinical use, these findings may be evaluated on other segmentation models, larger datasets, additional OCT devices, and with naturally occurring acquisition artifacts. 2026-11-12 Diagnostics, Vol. 16, Pages 3754: Robustness of U-Net Retinal Layer Segmentation to Controlled OCT Image Degradation

Diagnostics doi: 10.3390/diagnostics16223754

Authors: Michael R. Gardner

Background: Optical coherence tomography (OCT) retinal layer segmentation supports quantitative clinical assessment, but its robustness to different image degradation has not been systematically characterized. Methods: This study evaluates a U-Net trained on unmodified OCT5k scans under seven synthetic degradation families at five family-specific severity levels. The test set included 315 held-out B-scans from nine cases, with three cases each of age-related macular degeneration, diabetic macular edema, and healthy retinas. After ordered boundary decoding, two primary outcomes were calculated: boundary mean absolute error (MAE, pixels) and internal-layer Dice. Results: Clean images yielded macro-MAE of 3.66 pixels and macro-Dice of 0.934. At severity 5, MAE increased in five families and Dice decreased in all seven. Gaussian noise, contrast reduction, and global attenuation produced the largest deterioration, with macro-MAE/macro-Dice values of 94.35/0.715, 236.81/0.044, and 112.32/0.0004, respectively. Adjusted paired tests showed statistically significant deterioration in both outcomes for these three families; macro-Dice also showed declines under defocus, shadowing, and axial-resolution reduction, while speckle showed no significant change. Conclusions: These results indicate corruption- and metric-specific vulnerability in the tested U-Net. This study may inform the development of automated OCT image-quality screening. Before clinical use, these findings may be evaluated on other segmentation models, larger datasets, additional OCT devices, and with naturally occurring acquisition artifacts.

]]> Robustness of U-Net Retinal Layer Segmentation to Controlled OCT Image Degradation Michael R. Gardner doi: 10.3390/diagnostics16223754 Diagnostics 2026-11-12 Diagnostics 2026-11-12 16 22 Article 3754 10.3390/diagnostics16223754 https://www.mdpi.com/2075-4418/16/22/3754 Diagnostics, Vol. 16, Pages 3756: Early-Term Pneumopericardium After Cardiac Surgery https://www.mdpi.com/2075-4418/16/22/3756 Free air in the pericardial space is called pneumopericardium, a rare phenomenon. Increased intra-alveolar pressure may cause alveolar rupture, releasing air that travels to the pericardial space. This condition can occur following trauma or surgical interventions. In this case, we present a young female patient with pneumopericardium that developed early after open-heart surgery. Interestingly, the pleural spaces were not opened during the initial operation, and hemodynamic stability was maintained despite the massive mediastinal air that developed. The case was treated surgically due to the possible risk of infection associated with the Dacron graft in the mediastinum. 2026-11-12 Diagnostics, Vol. 16, Pages 3756: Early-Term Pneumopericardium After Cardiac Surgery

Diagnostics doi: 10.3390/diagnostics16223756

Authors: Mesut Engin Omer Serbetcioglu Ufuk Aydın Yusuf Ata

Free air in the pericardial space is called pneumopericardium, a rare phenomenon. Increased intra-alveolar pressure may cause alveolar rupture, releasing air that travels to the pericardial space. This condition can occur following trauma or surgical interventions. In this case, we present a young female patient with pneumopericardium that developed early after open-heart surgery. Interestingly, the pleural spaces were not opened during the initial operation, and hemodynamic stability was maintained despite the massive mediastinal air that developed. The case was treated surgically due to the possible risk of infection associated with the Dacron graft in the mediastinum.

]]> Early-Term Pneumopericardium After Cardiac Surgery Mesut Engin Omer Serbetcioglu Ufuk Aydın Yusuf Ata doi: 10.3390/diagnostics16223756 Diagnostics 2026-11-12 Diagnostics 2026-11-12 16 22 Interesting Images 3756 10.3390/diagnostics16223756 https://www.mdpi.com/2075-4418/16/22/3756 Diagnostics, Vol. 16, Pages 3755: Clinical Significance of Abnormal First-Trimester Chorionic Villus Sampling After Mosaic Embryo Transfer: A Prospective Study with Confirmatory Amniocentesis https://www.mdpi.com/2075-4418/16/22/3755 Background/Objectives: Prenatal outcomes after mosaic embryo transfer are generally reassuring. However, evidence remains limited on how an abnormal first-trimester chorionic villus sampling (CVS) result should be interpreted. We evaluated first-trimester CVS findings after mosaic embryo transfer and examined their relationship with the original preimplantation genetic testing for aneuploidy (PGT-A) results and subsequent amniocentesis. Methods: This prospective observational study included 183 CVS specimens obtained from placentas corresponding to PGT-A-designated mosaic embryos. Uncultured chorionic villi were analyzed using the same next-generation sequencing platform used for PGT-A. Abnormal CVS findings were compared with the original PGT-A results, and all nine pregnancies with an abnormal CVS result underwent diagnostic amniocentesis. Results: Of the 183 CVS specimens, 174 (95.1%) were euploid and nine (4.9%; exact 95% confidence interval, 2.27–9.13%) were abnormal. Among the nine abnormal findings, three involved the same chromosome or chromosomal region reported by PGT-A, whereas six involved a different chromosome or region. Amniocentesis showed a euploid result in eight cases, which were classified as confirmed confined placental mosaicism. In the remaining case, mosaicism was also detected in amniotic fluid and was classified as confirmed fetal mosaicism. Conclusions: This is the largest published series specifically evaluating first-trimester CVS after mosaic embryo transfer. Abnormal CVS findings were uncommon, and eight of the nine abnormal findings were confined to the placenta. Furthermore, six involved a chromosome or chromosomal region different from that reported by PGT-A. Therefore, an abnormal CVS result does not necessarily indicate fetal involvement or persistence of the original PGT-A abnormality. Amniocentesis is required to clarify the fetal chromosomal status. 2026-11-12 Diagnostics, Vol. 16, Pages 3755: Clinical Significance of Abnormal First-Trimester Chorionic Villus Sampling After Mosaic Embryo Transfer: A Prospective Study with Confirmatory Amniocentesis

Diagnostics doi: 10.3390/diagnostics16223755

Authors: Pin-Yao Lin Chun-I Lee En-Hui Cheng Yi-Ping Pai Chun-Chia Huang Ming-Jer Chen Tzu-Ning Yu Wei-Che Lo Tsung-Hsien Lee Maw-Sheng Lee

Background/Objectives: Prenatal outcomes after mosaic embryo transfer are generally reassuring. However, evidence remains limited on how an abnormal first-trimester chorionic villus sampling (CVS) result should be interpreted. We evaluated first-trimester CVS findings after mosaic embryo transfer and examined their relationship with the original preimplantation genetic testing for aneuploidy (PGT-A) results and subsequent amniocentesis. Methods: This prospective observational study included 183 CVS specimens obtained from placentas corresponding to PGT-A-designated mosaic embryos. Uncultured chorionic villi were analyzed using the same next-generation sequencing platform used for PGT-A. Abnormal CVS findings were compared with the original PGT-A results, and all nine pregnancies with an abnormal CVS result underwent diagnostic amniocentesis. Results: Of the 183 CVS specimens, 174 (95.1%) were euploid and nine (4.9%; exact 95% confidence interval, 2.27–9.13%) were abnormal. Among the nine abnormal findings, three involved the same chromosome or chromosomal region reported by PGT-A, whereas six involved a different chromosome or region. Amniocentesis showed a euploid result in eight cases, which were classified as confirmed confined placental mosaicism. In the remaining case, mosaicism was also detected in amniotic fluid and was classified as confirmed fetal mosaicism. Conclusions: This is the largest published series specifically evaluating first-trimester CVS after mosaic embryo transfer. Abnormal CVS findings were uncommon, and eight of the nine abnormal findings were confined to the placenta. Furthermore, six involved a chromosome or chromosomal region different from that reported by PGT-A. Therefore, an abnormal CVS result does not necessarily indicate fetal involvement or persistence of the original PGT-A abnormality. Amniocentesis is required to clarify the fetal chromosomal status.

]]> Clinical Significance of Abnormal First-Trimester Chorionic Villus Sampling After Mosaic Embryo Transfer: A Prospective Study with Confirmatory Amniocentesis Pin-Yao Lin Chun-I Lee En-Hui Cheng Yi-Ping Pai Chun-Chia Huang Ming-Jer Chen Tzu-Ning Yu Wei-Che Lo Tsung-Hsien Lee Maw-Sheng Lee doi: 10.3390/diagnostics16223755 Diagnostics 2026-11-12 Diagnostics 2026-11-12 16 22 Article 3755 10.3390/diagnostics16223755 https://www.mdpi.com/2075-4418/16/22/3755 Diagnostics, Vol. 16, Pages 3753: Explainable Transfer Learning for Brain Tumor MRI Classification: Leakage-Aware Evaluation, Grey Wolf Optimizer-Based Hyperparameter Tuning, and Quantitative Attribution Analysis https://www.mdpi.com/2075-4418/16/22/3753 Background/Objectives: Accurate MRI-based brain tumor classification requires leakage-free performance estimates and inspectable decisions. We compared pretrained convolutional neural networks (CNNs), evaluated Grey Wolf Optimizer (GWO)-based hyperparameter tuning against alternative search strategies, and quantified Grad-CAM explanations. Methods: Seven ImageNet-pretrained CNNs were compared with duplicate-aware 10-fold cross-validation on 5966 images of a public four-class dataset; 1057 images were held out. GWO tuning of VGG16 was compared with five other search strategies at an equal budget. Ablation, cost-sensitive training, external validation (BDNeuro-MRI), and Grad-CAM analyses of all test images were performed. Results: VGG16 had the highest cross-validation accuracy under the original protocol (96.73 ± 1.24%) but not under full fine-tuning. GWO-VGG16 reached 98.68% hold-out accuracy (95% CI 97.92–99.34%). Because 39.7% of test images had a duplicate in the development data, accuracy was also assessed on 637 duplicate-free test images (98.27%; 95% CI 96.93–99.03%) and on 1888 non-overlapping external images (87.29%; 95% CI 85.75–88.77%). GWO was not superior to alternative search strategies. Grad-CAM maps showed little border attention and were model-dependent, but lesion localization remained unverified. Conclusions: High internal accuracy did not fully transfer to external data; without patient-level validation and expert annotations, the framework remains a research-stage tool, not a validated diagnostic system. 2026-11-12 Diagnostics, Vol. 16, Pages 3753: Explainable Transfer Learning for Brain Tumor MRI Classification: Leakage-Aware Evaluation, Grey Wolf Optimizer-Based Hyperparameter Tuning, and Quantitative Attribution Analysis

Diagnostics doi: 10.3390/diagnostics16223753

Authors: Neriman Akdam Yusuf Eryesil Murat Koklu

Background/Objectives: Accurate MRI-based brain tumor classification requires leakage-free performance estimates and inspectable decisions. We compared pretrained convolutional neural networks (CNNs), evaluated Grey Wolf Optimizer (GWO)-based hyperparameter tuning against alternative search strategies, and quantified Grad-CAM explanations. Methods: Seven ImageNet-pretrained CNNs were compared with duplicate-aware 10-fold cross-validation on 5966 images of a public four-class dataset; 1057 images were held out. GWO tuning of VGG16 was compared with five other search strategies at an equal budget. Ablation, cost-sensitive training, external validation (BDNeuro-MRI), and Grad-CAM analyses of all test images were performed. Results: VGG16 had the highest cross-validation accuracy under the original protocol (96.73 ± 1.24%) but not under full fine-tuning. GWO-VGG16 reached 98.68% hold-out accuracy (95% CI 97.92–99.34%). Because 39.7% of test images had a duplicate in the development data, accuracy was also assessed on 637 duplicate-free test images (98.27%; 95% CI 96.93–99.03%) and on 1888 non-overlapping external images (87.29%; 95% CI 85.75–88.77%). GWO was not superior to alternative search strategies. Grad-CAM maps showed little border attention and were model-dependent, but lesion localization remained unverified. Conclusions: High internal accuracy did not fully transfer to external data; without patient-level validation and expert annotations, the framework remains a research-stage tool, not a validated diagnostic system.

]]> Explainable Transfer Learning for Brain Tumor MRI Classification: Leakage-Aware Evaluation, Grey Wolf Optimizer-Based Hyperparameter Tuning, and Quantitative Attribution Analysis Neriman Akdam Yusuf Eryesil Murat Koklu doi: 10.3390/diagnostics16223753 Diagnostics 2026-11-12 Diagnostics 2026-11-12 16 22 Article 3753 10.3390/diagnostics16223753 https://www.mdpi.com/2075-4418/16/22/3753 Diagnostics, Vol. 16, Pages 3752: Wearable- and Vision-Based Gait Models for Predicting Future Falls in Older Adults: A Systematic Review of Performance, Validation, and Clinical Readiness https://www.mdpi.com/2075-4418/16/22/3752 Background/Objectives: We reviewed the performance, validation and clinical readiness of wearable- and vision-based models predicting future falls. Methods: Nine databases and supplementary sources were searched for reports published in 2000–20 July 2026 (retrospective PROSPERO registration: CRD420261502037). Eligible populations had a minimum, mean or median age ≥60 years or separable older-adult results. Screening, extraction and appraisal used single-reviewer assessment with second-reviewer verification, rather than independent duplication. Ten of 47 reports (21.28%) lacked complete-article access. Cohort families were synthesized without meta-analysis; PROBAST+AI appraisal was restricted to complete articles. Results: The 47 reports represented 37 cohort families (15–1705 participants; horizons 7 days–5 years). Representative AUCs ranged from 0.51 to 0.99 across 26 families; 24 estimates were apparent, internally validated or validation-unverified. The only independent-cohort evaluation of published models yielded AUCs of 0.49–0.59. Retained domain-level appraisals classified all 37 complete-article evaluations as high risk of bias. Calibration intercept and slope appeared in one report (2.13%); none reported decision curve analysis, net benefit or clinical impact. Conclusions: Interpretability is limited by high risk of bias, sparse events, limited independent validation and missing calibration. The evidence does not support routine deployment; this concerns evidentiary readiness rather than technical potential. Funding: King Salman Center for Disability Research. 2026-11-12 Diagnostics, Vol. 16, Pages 3752: Wearable- and Vision-Based Gait Models for Predicting Future Falls in Older Adults: A Systematic Review of Performance, Validation, and Clinical Readiness

Diagnostics doi: 10.3390/diagnostics16223752

Authors: Majed S. Alsanea Yosef Hasan Jbara Alshimaa Hamdy Ismail Farha Mujeeb Ahmed Shaikh Mohammed Gh. Alzahrani

Background/Objectives: We reviewed the performance, validation and clinical readiness of wearable- and vision-based models predicting future falls. Methods: Nine databases and supplementary sources were searched for reports published in 2000–20 July 2026 (retrospective PROSPERO registration: CRD420261502037). Eligible populations had a minimum, mean or median age ≥60 years or separable older-adult results. Screening, extraction and appraisal used single-reviewer assessment with second-reviewer verification, rather than independent duplication. Ten of 47 reports (21.28%) lacked complete-article access. Cohort families were synthesized without meta-analysis; PROBAST+AI appraisal was restricted to complete articles. Results: The 47 reports represented 37 cohort families (15–1705 participants; horizons 7 days–5 years). Representative AUCs ranged from 0.51 to 0.99 across 26 families; 24 estimates were apparent, internally validated or validation-unverified. The only independent-cohort evaluation of published models yielded AUCs of 0.49–0.59. Retained domain-level appraisals classified all 37 complete-article evaluations as high risk of bias. Calibration intercept and slope appeared in one report (2.13%); none reported decision curve analysis, net benefit or clinical impact. Conclusions: Interpretability is limited by high risk of bias, sparse events, limited independent validation and missing calibration. The evidence does not support routine deployment; this concerns evidentiary readiness rather than technical potential. Funding: King Salman Center for Disability Research.

]]> Wearable- and Vision-Based Gait Models for Predicting Future Falls in Older Adults: A Systematic Review of Performance, Validation, and Clinical Readiness Majed S. Alsanea Yosef Hasan Jbara Alshimaa Hamdy Ismail Farha Mujeeb Ahmed Shaikh Mohammed Gh. Alzahrani doi: 10.3390/diagnostics16223752 Diagnostics 2026-11-12 Diagnostics 2026-11-12 16 22 Systematic Review 3752 10.3390/diagnostics16223752 https://www.mdpi.com/2075-4418/16/22/3752 Diagnostics, Vol. 16, Pages 3751: Genetic Polymorphisms in Apoptosis-Related Genes XAF1 and XIAP Are Associated with Clinical Outcomes in Pediatric Ewing Sarcoma https://www.mdpi.com/2075-4418/16/22/3751 Background/Objectives: Ewing sarcoma (ES) is an aggressive malignant cancer with a higher incidence in adolescents and young adults. Despite multimodal therapy, prognosis remains poor, particularly in metastatic and recurrence cases. Dysregulation of apoptosis is central to ES tumorigenesis; however, the impact of polymorphisms in apoptotic regulators on clinical outcomes remains unclear. This study investigated the association between single-nucleotide polymorphisms (SNPs) in the apoptotic pathway genes XAF1 and XIAP and their respective protein expression in ES outcomes. Methods: A cross-sectional study was conducted on ES samples from paraffin blocks (n = 55). Genotyping for selected SNPs and immunohistochemistry for XAF1 and XIAP expression were performed. The cohort included 41 pediatric and 14 non-pediatric cases. Statistical associations were analyzed between genotypes, age groups, protein expression, and recurrence. Results: The male sex (61.8%) and bone site (75.5%) were prevalent, while recurrence (30.9%) and metastasis (14.5%) were frequent outcomes. There was low or absent XAF1 expression (<1.2 μm2) in 75.5% of all ES cases, and 54.9% showed higher XIAP expression (≥16.4 μm2). The A allele present in the dominant group (AA + AG) of the rs3785793 [A/G] XAF1 gene, showed significantly lower XAF1 expression (p = 0.043) and was associated with recurrence in comparison to the GG genotype in pediatric ES. Conclusions: ES showed low or absent protein XAF1 expression and high XIAP expression. The wild-type A-allele of XAF1 rs3785793 was associated with decreased protein expression and increased recurrence outcome in pediatric ES. These findings suggest XAF1 polymorphism might be a potential biomarker for outcomes in ES, warranting further validation in larger prospective cohorts. 2026-11-12 Diagnostics, Vol. 16, Pages 3751: Genetic Polymorphisms in Apoptosis-Related Genes XAF1 and XIAP Are Associated with Clinical Outcomes in Pediatric Ewing Sarcoma

Diagnostics doi: 10.3390/diagnostics16223751

Authors: Leonardo Vinícius Barbosa Ana Clara de Almeida Cui Tu Rafael Roesler Caroline Brunetto de Farias Roberto Rosati Luciane Regina Cavalli Arutha Kulasinghe Fernando Souza-Fonseca Guimarães Lucia de Noronha Cleber Machado-Souza

Background/Objectives: Ewing sarcoma (ES) is an aggressive malignant cancer with a higher incidence in adolescents and young adults. Despite multimodal therapy, prognosis remains poor, particularly in metastatic and recurrence cases. Dysregulation of apoptosis is central to ES tumorigenesis; however, the impact of polymorphisms in apoptotic regulators on clinical outcomes remains unclear. This study investigated the association between single-nucleotide polymorphisms (SNPs) in the apoptotic pathway genes XAF1 and XIAP and their respective protein expression in ES outcomes. Methods: A cross-sectional study was conducted on ES samples from paraffin blocks (n = 55). Genotyping for selected SNPs and immunohistochemistry for XAF1 and XIAP expression were performed. The cohort included 41 pediatric and 14 non-pediatric cases. Statistical associations were analyzed between genotypes, age groups, protein expression, and recurrence. Results: The male sex (61.8%) and bone site (75.5%) were prevalent, while recurrence (30.9%) and metastasis (14.5%) were frequent outcomes. There was low or absent XAF1 expression (<1.2 μm2) in 75.5% of all ES cases, and 54.9% showed higher XIAP expression (≥16.4 μm2). The A allele present in the dominant group (AA + AG) of the rs3785793 [A/G] XAF1 gene, showed significantly lower XAF1 expression (p = 0.043) and was associated with recurrence in comparison to the GG genotype in pediatric ES. Conclusions: ES showed low or absent protein XAF1 expression and high XIAP expression. The wild-type A-allele of XAF1 rs3785793 was associated with decreased protein expression and increased recurrence outcome in pediatric ES. These findings suggest XAF1 polymorphism might be a potential biomarker for outcomes in ES, warranting further validation in larger prospective cohorts.

]]> Genetic Polymorphisms in Apoptosis-Related Genes XAF1 and XIAP Are Associated with Clinical Outcomes in Pediatric Ewing Sarcoma Leonardo Vinícius Barbosa Ana Clara de Almeida Cui Tu Rafael Roesler Caroline Brunetto de Farias Roberto Rosati Luciane Regina Cavalli Arutha Kulasinghe Fernando Souza-Fonseca Guimarães Lucia de Noronha Cleber Machado-Souza doi: 10.3390/diagnostics16223751 Diagnostics 2026-11-12 Diagnostics 2026-11-12 16 22 Article 3751 10.3390/diagnostics16223751 https://www.mdpi.com/2075-4418/16/22/3751 Diagnostics, Vol. 16, Pages 3750: Association of the Cholesterol–High-Density Lipoprotein–Glucose Index with Large-Artery Atherosclerotic Versus Cardioembolic Stroke: A Single-Center Retrospective Study https://www.mdpi.com/2075-4418/16/22/3750 Background/Objectives: We aimed to assess the association of the cholesterol–high-density lipoprotein–glucose index (CHG) with large-artery atherosclerotic stroke (LAA) versus cardioembolic stroke (CE), and to compare its discrimination and incremental value beyond a clinical model with those of the triglyceride–glucose index (TyG). Methods: This single-center retrospective study consecutively screened patients hospitalized with ischemic stroke at Beijing Anzhen Hospital, Capital Medical University, from September 2024 to August 2025 and included eligible patients with acute LAA or CE. CHG and TyG were calculated from the first examination results after admission. Missing BMI values were handled using 20 multiple imputations. Logistic regression, restricted cubic splines, and exploratory subgroup analyses were used to evaluate associations, with further adjustment for lipid-lowering and glucose-lowering medication use before the current stroke onset. Firth-penalized regression was also used to assess the robustness of the association estimates. Model performance was evaluated using 1000 paired outcome-stratified bootstrap resamples, comparing CHG, TyG, and joint modeling of the three component indicators and estimating differences in corrected AUC and their 95% confidence intervals. Results: The study included 921 patients, comprising 790 with LAA and 131 with CE. After multivariable adjustment, each 1-standard-deviation increase in CHG was associated with an odds ratio of 2.83 for LAA versus CE (95% confidence interval: 2.20–3.65, p < 0.001), with a nonlinear association (p for nonlinearity = 0.003). The OR in the Firth sensitivity analysis was 2.77 (95% confidence interval: 2.17–3.59). The single-index AUCs of CHG and TyG were 0.725 and 0.662, respectively (paired DeLong p < 0.001). Adding CHG increased the bootstrap-corrected AUC of the clinical model from 0.647 to 0.743 and reduced the corrected Brier score from 0.119 to 0.105. The difference in corrected AUC between the CHG-enhanced model and the TyG-enhanced model was 0.051 (95% confidence interval: 0.025–0.079), whereas its difference from the model jointly including the three component indicators remained uncertain. The direction of the main associations was consistent in sensitivity analyses, and no clear subgroup interactions were identified. Conclusions: In this cohort, higher CHG was positively associated with LAA versus CE after adjustment for measured covariates. Its enhanced model had higher discrimination than the TyG-enhanced model in internal validation, but its advantage over joint modeling of the component indicators remained uncertain. This was a single-center retrospective study with a substantial imbalance in group sizes, and residual confounding may remain. All performance estimates were derived from internal validation. The clinical utility of CHG and its applicability across centers have not been established and require independent external validation. 2026-11-12 Diagnostics, Vol. 16, Pages 3750: Association of the Cholesterol–High-Density Lipoprotein–Glucose Index with Large-Artery Atherosclerotic Versus Cardioembolic Stroke: A Single-Center Retrospective Study

Diagnostics doi: 10.3390/diagnostics16223750

Authors: Yilian Zhang Yan Ma Lupeng Wang Xiao Zhang Hui Yuan

Background/Objectives: We aimed to assess the association of the cholesterol–high-density lipoprotein–glucose index (CHG) with large-artery atherosclerotic stroke (LAA) versus cardioembolic stroke (CE), and to compare its discrimination and incremental value beyond a clinical model with those of the triglyceride–glucose index (TyG). Methods: This single-center retrospective study consecutively screened patients hospitalized with ischemic stroke at Beijing Anzhen Hospital, Capital Medical University, from September 2024 to August 2025 and included eligible patients with acute LAA or CE. CHG and TyG were calculated from the first examination results after admission. Missing BMI values were handled using 20 multiple imputations. Logistic regression, restricted cubic splines, and exploratory subgroup analyses were used to evaluate associations, with further adjustment for lipid-lowering and glucose-lowering medication use before the current stroke onset. Firth-penalized regression was also used to assess the robustness of the association estimates. Model performance was evaluated using 1000 paired outcome-stratified bootstrap resamples, comparing CHG, TyG, and joint modeling of the three component indicators and estimating differences in corrected AUC and their 95% confidence intervals. Results: The study included 921 patients, comprising 790 with LAA and 131 with CE. After multivariable adjustment, each 1-standard-deviation increase in CHG was associated with an odds ratio of 2.83 for LAA versus CE (95% confidence interval: 2.20–3.65, p < 0.001), with a nonlinear association (p for nonlinearity = 0.003). The OR in the Firth sensitivity analysis was 2.77 (95% confidence interval: 2.17–3.59). The single-index AUCs of CHG and TyG were 0.725 and 0.662, respectively (paired DeLong p < 0.001). Adding CHG increased the bootstrap-corrected AUC of the clinical model from 0.647 to 0.743 and reduced the corrected Brier score from 0.119 to 0.105. The difference in corrected AUC between the CHG-enhanced model and the TyG-enhanced model was 0.051 (95% confidence interval: 0.025–0.079), whereas its difference from the model jointly including the three component indicators remained uncertain. The direction of the main associations was consistent in sensitivity analyses, and no clear subgroup interactions were identified. Conclusions: In this cohort, higher CHG was positively associated with LAA versus CE after adjustment for measured covariates. Its enhanced model had higher discrimination than the TyG-enhanced model in internal validation, but its advantage over joint modeling of the component indicators remained uncertain. This was a single-center retrospective study with a substantial imbalance in group sizes, and residual confounding may remain. All performance estimates were derived from internal validation. The clinical utility of CHG and its applicability across centers have not been established and require independent external validation.

]]> Association of the Cholesterol–High-Density Lipoprotein–Glucose Index with Large-Artery Atherosclerotic Versus Cardioembolic Stroke: A Single-Center Retrospective Study Yilian Zhang Yan Ma Lupeng Wang Xiao Zhang Hui Yuan doi: 10.3390/diagnostics16223750 Diagnostics 2026-11-12 Diagnostics 2026-11-12 16 22 Article 3750 10.3390/diagnostics16223750 https://www.mdpi.com/2075-4418/16/22/3750 Diagnostics, Vol. 16, Pages 3748: Diagnostic Performance of Data-Driven MRI Habitat Analysis for Preoperative Prediction of IDH Status in Adult Gliomas: A Systematic Review and Diagnostic Accuracy Meta-Analysis https://www.mdpi.com/2075-4418/16/22/3748 Background/Objectives: Isocitrate dehydrogenase (IDH) status is important for the classification and prognosis of adult gliomas. Whole-tumor MRI summary measures may obscure intratumoral spatial heterogeneity, whereas data-driven habitat analysis identifies imaging-defined tumor subregions and may better capture this heterogeneity. This study aimed to evaluate the diagnostic performance of MRI habitat analysis for preoperative prediction of IDH status. Methods: We searched PubMed, Embase, Web of Science Core Collection, China National Knowledge Infrastructure (CNKI), and Wanfang Data from database inception through 22 August 2026. Eligible studies used data-driven MRI habitat analysis to predict IDH status in adult gliomas. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. Sensitivity and specificity were pooled using a bivariate random-effects model. We also performed sensitivity analyses, univariable meta-regression, subgroup analyses, and Radiomics Quality Score 2.0 (RQS 2.0) assessment. The protocol was registered in PROSPERO (CRD420261489645). Results: Eighteen reports were included in the systematic review, and 13 independent studies involving 1236 patients contributed to the meta-analysis. Pooled sensitivity and specificity were 0.78 (95% CI, 0.70–0.84) and 0.85 (95% CI, 0.79–0.89), respectively, with an SROC AUC of 0.89 (95% CI, 0.86–0.91). I2 was 82.1% for sensitivity and 71.3% for specificity. Excluding two studies with approximately reconstructed 2 × 2 tables did not materially change the pooled estimates. Radiomics studies and studies using ≥4 habitats showed higher specificity and lower sensitivity, but their overlap limited separate interpretation of feature type and habitat number. Conclusions: MRI habitat analysis showed promising diagnostic performance for preoperative prediction of IDH status in adult gliomas. However, limited external validation and incomplete assessment of reproducibility and clinical utility remain barriers to clinical translation. Future prospective multicenter studies should further evaluate habitat stability, model calibration, and clinical net benefit. 2026-11-12 Diagnostics, Vol. 16, Pages 3748: Diagnostic Performance of Data-Driven MRI Habitat Analysis for Preoperative Prediction of IDH Status in Adult Gliomas: A Systematic Review and Diagnostic Accuracy Meta-Analysis

Diagnostics doi: 10.3390/diagnostics16223748

Authors: Qiang Wei Panhui Liu Kexin Xu Yinghua Wu

Background/Objectives: Isocitrate dehydrogenase (IDH) status is important for the classification and prognosis of adult gliomas. Whole-tumor MRI summary measures may obscure intratumoral spatial heterogeneity, whereas data-driven habitat analysis identifies imaging-defined tumor subregions and may better capture this heterogeneity. This study aimed to evaluate the diagnostic performance of MRI habitat analysis for preoperative prediction of IDH status. Methods: We searched PubMed, Embase, Web of Science Core Collection, China National Knowledge Infrastructure (CNKI), and Wanfang Data from database inception through 22 August 2026. Eligible studies used data-driven MRI habitat analysis to predict IDH status in adult gliomas. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. Sensitivity and specificity were pooled using a bivariate random-effects model. We also performed sensitivity analyses, univariable meta-regression, subgroup analyses, and Radiomics Quality Score 2.0 (RQS 2.0) assessment. The protocol was registered in PROSPERO (CRD420261489645). Results: Eighteen reports were included in the systematic review, and 13 independent studies involving 1236 patients contributed to the meta-analysis. Pooled sensitivity and specificity were 0.78 (95% CI, 0.70–0.84) and 0.85 (95% CI, 0.79–0.89), respectively, with an SROC AUC of 0.89 (95% CI, 0.86–0.91). I2 was 82.1% for sensitivity and 71.3% for specificity. Excluding two studies with approximately reconstructed 2 × 2 tables did not materially change the pooled estimates. Radiomics studies and studies using ≥4 habitats showed higher specificity and lower sensitivity, but their overlap limited separate interpretation of feature type and habitat number. Conclusions: MRI habitat analysis showed promising diagnostic performance for preoperative prediction of IDH status in adult gliomas. However, limited external validation and incomplete assessment of reproducibility and clinical utility remain barriers to clinical translation. Future prospective multicenter studies should further evaluate habitat stability, model calibration, and clinical net benefit.

]]> Diagnostic Performance of Data-Driven MRI Habitat Analysis for Preoperative Prediction of IDH Status in Adult Gliomas: A Systematic Review and Diagnostic Accuracy Meta-Analysis Qiang Wei Panhui Liu Kexin Xu Yinghua Wu doi: 10.3390/diagnostics16223748 Diagnostics 2026-11-12 Diagnostics 2026-11-12 16 22 Systematic Review 3748 10.3390/diagnostics16223748 https://www.mdpi.com/2075-4418/16/22/3748 Diagnostics, Vol. 16, Pages 3749: Calibration and Cross-Dataset Behavior in Malaria Microscopy with Parameter-Efficient Fine-Tuning: A Matched LoRA–PiSSA Evaluation https://www.mdpi.com/2075-4418/16/22/3749 Background/Objectives: Reliable evaluation of deep-learning methods for malaria microscopy requires assessing both classification performance and the quality of predicted infection probabilities across datasets. We compared low-rank adaptation (LoRA) and principal singular values and singular vectors adaptation (PiSSA) under matched parameter-efficient fine-tuning (PEFT). Methods: An ImageNet-pretrained vision transformer (ViT-B/16) was adapted at ranks 2, 4, 8, and 16 using 27,558 National Institutes of Health (NIH) malaria cell images. One NIH grouped partition was held fixed across paired training seeds 42, 123, and 456. Models were evaluated on the NIH test split and, without target-domain adaptation, on BBBC041 P. vivax cell crops. The analysis was also replicated in invasive ductal carcinoma (IDC) histopathology. External probability and threshold-transfer analyses were post hoc. Results: Across LoRA and PiSSA configurations, NIH area under the receiver operating characteristic curve (ROC–AUC) ranged from 0.9960 to 0.9970. PiSSA had lower rank-level mean Brier scores and expected calibration error (ECE) at every evaluated rank in NIH and IDC, although paired-run differences varied. On BBBC041, PiSSA-r16 achieved the highest PEFT ROC–AUC (0.8451) and area under the precision–recall curve (PR–AUC, 0.1588), while fully trained reference models performed better. Across all 12 matched external comparisons, PiSSA had lower overall Brier scores and ECE but higher infected-cell Brier scores. PiSSA had lower sensitivity at NIH-derived thresholds in 11 of 12 comparisons. All PEFT models overpredicted infection relative to the observed 2.70% prevalence. Conclusions: Nearly identical internal discrimination concealed differences in external probability behavior and class-specific errors. PiSSA reduced overprediction, but neither adapter achieved adequate external calibration. 2026-11-12 Diagnostics, Vol. 16, Pages 3749: Calibration and Cross-Dataset Behavior in Malaria Microscopy with Parameter-Efficient Fine-Tuning: A Matched LoRA–PiSSA Evaluation

Diagnostics doi: 10.3390/diagnostics16223749

Authors: Sorio Boit Rajvardhan Patil Tiehang Duan

Background/Objectives: Reliable evaluation of deep-learning methods for malaria microscopy requires assessing both classification performance and the quality of predicted infection probabilities across datasets. We compared low-rank adaptation (LoRA) and principal singular values and singular vectors adaptation (PiSSA) under matched parameter-efficient fine-tuning (PEFT). Methods: An ImageNet-pretrained vision transformer (ViT-B/16) was adapted at ranks 2, 4, 8, and 16 using 27,558 National Institutes of Health (NIH) malaria cell images. One NIH grouped partition was held fixed across paired training seeds 42, 123, and 456. Models were evaluated on the NIH test split and, without target-domain adaptation, on BBBC041 P. vivax cell crops. The analysis was also replicated in invasive ductal carcinoma (IDC) histopathology. External probability and threshold-transfer analyses were post hoc. Results: Across LoRA and PiSSA configurations, NIH area under the receiver operating characteristic curve (ROC–AUC) ranged from 0.9960 to 0.9970. PiSSA had lower rank-level mean Brier scores and expected calibration error (ECE) at every evaluated rank in NIH and IDC, although paired-run differences varied. On BBBC041, PiSSA-r16 achieved the highest PEFT ROC–AUC (0.8451) and area under the precision–recall curve (PR–AUC, 0.1588), while fully trained reference models performed better. Across all 12 matched external comparisons, PiSSA had lower overall Brier scores and ECE but higher infected-cell Brier scores. PiSSA had lower sensitivity at NIH-derived thresholds in 11 of 12 comparisons. All PEFT models overpredicted infection relative to the observed 2.70% prevalence. Conclusions: Nearly identical internal discrimination concealed differences in external probability behavior and class-specific errors. PiSSA reduced overprediction, but neither adapter achieved adequate external calibration.

]]> Calibration and Cross-Dataset Behavior in Malaria Microscopy with Parameter-Efficient Fine-Tuning: A Matched LoRA–PiSSA Evaluation Sorio Boit Rajvardhan Patil Tiehang Duan doi: 10.3390/diagnostics16223749 Diagnostics 2026-11-12 Diagnostics 2026-11-12 16 22 Article 3749 10.3390/diagnostics16223749 https://www.mdpi.com/2075-4418/16/22/3749 Diagnostics, Vol. 16, Pages 3747: Association Between Trapezius Lateral Shear Strain and Perceived Stiffness Assessed with Continuous Shear Wave Imaging: A Prospective Observational Study https://www.mdpi.com/2075-4418/16/22/3747 Background/Objectives: We explored whether lateral shear strain (L-str), an imaging-derived parameter estimated from oscillatory displacement in continuous shear wave imaging (C-SWI), was associated with perceived shoulder stiffness. Methods: In this prospective observational study, 12 adults with chronic shoulder stiffness underwent bilateral C-SWI of the upper and lower trapezius and symptom evaluation at baseline and 4-week follow-up. During follow-up, participants undertook a general exercise routine provided independently of the study. Results: No C-SWI parameter changed significantly at the group level after multiplicity correction. Change in bilateral averaged all-muscle L-str was inversely associated with change in stiffness assessed using a visual analog scale (VAS) (Pearson r = −0.804, 95% confidence interval −0.94 to −0.43, p = 0.0016). The false-discovery-rate q value was 0.029 within 18 L-str–symptom comparisons, 0.058 with 36 pooled symptom comparisons, and 0.109 with all 68 comparisons; the Spearman correlation did not remain significant (ρ = −0.77, q = 0.063). After adjustment for baseline stiffness, the partial correlation was −0.51 (p = 0.11). Conclusions: These exploratory findings are sensitive to analysis choices and baseline adjustment, and regression to the mean cannot be excluded. L-str has not been independently validated as a measure of tissue deformation; confirmation is required. 2026-11-12 Diagnostics, Vol. 16, Pages 3747: Association Between Trapezius Lateral Shear Strain and Perceived Stiffness Assessed with Continuous Shear Wave Imaging: A Prospective Observational Study

Diagnostics doi: 10.3390/diagnostics16223747

Authors: Hitoshi Shitara Ren Koda Ryosuke Miyamoto Fukuhisa Ino Yoshiki Yamakoshi Hirotaka Chikuda

Background/Objectives: We explored whether lateral shear strain (L-str), an imaging-derived parameter estimated from oscillatory displacement in continuous shear wave imaging (C-SWI), was associated with perceived shoulder stiffness. Methods: In this prospective observational study, 12 adults with chronic shoulder stiffness underwent bilateral C-SWI of the upper and lower trapezius and symptom evaluation at baseline and 4-week follow-up. During follow-up, participants undertook a general exercise routine provided independently of the study. Results: No C-SWI parameter changed significantly at the group level after multiplicity correction. Change in bilateral averaged all-muscle L-str was inversely associated with change in stiffness assessed using a visual analog scale (VAS) (Pearson r = −0.804, 95% confidence interval −0.94 to −0.43, p = 0.0016). The false-discovery-rate q value was 0.029 within 18 L-str–symptom comparisons, 0.058 with 36 pooled symptom comparisons, and 0.109 with all 68 comparisons; the Spearman correlation did not remain significant (ρ = −0.77, q = 0.063). After adjustment for baseline stiffness, the partial correlation was −0.51 (p = 0.11). Conclusions: These exploratory findings are sensitive to analysis choices and baseline adjustment, and regression to the mean cannot be excluded. L-str has not been independently validated as a measure of tissue deformation; confirmation is required.

]]> Association Between Trapezius Lateral Shear Strain and Perceived Stiffness Assessed with Continuous Shear Wave Imaging: A Prospective Observational Study Hitoshi Shitara Ren Koda Ryosuke Miyamoto Fukuhisa Ino Yoshiki Yamakoshi Hirotaka Chikuda doi: 10.3390/diagnostics16223747 Diagnostics 2026-11-12 Diagnostics 2026-11-12 16 22 Article 3747 10.3390/diagnostics16223747 https://www.mdpi.com/2075-4418/16/22/3747 Diagnostics, Vol. 16, Pages 3746: Beyond Bronchospasm: Cardiovascular Involvement in Severe Asthma https://www.mdpi.com/2075-4418/16/22/3746 Background: Severe asthma and cardiovascular disease can coexist, mimic one another, and interact through respiratory mechanics and treatment. This narrative review examines these relationships and their implications for intensive care. Main findings: Conventional and tissue Doppler studies identified cardiac abnormalities in asthma before widespread use of speckle tracking in this field. Subsequent deformation studies include predominantly pediatric or non-ICU populations, alongside limited adult acute severe-asthma evidence. Their findings are heterogeneous and largely observational. During exacerbations, dynamic hyperinflation, intrinsic positive end-expiratory pressure, pleural-pressure swings, right-ventricular loading, ventricular interdependence, gas-exchange abnormalities, adrenergic stimulation, and ventilation may alter filling and forward flow without primary cardiomyopathy. Conversely, heart failure with preserved ejection fraction can present with wheezing, but neither B-lines nor an isolated echocardiographic filling index establishes that diagnosis. Four ICU scenarios illustrate low flow despite high ejection fraction, post-intubation shock, congestion with preserved ejection fraction, and arrhythmia with transient dysfunction. Strain may help characterize serial changes but is load dependent; its incremental clinical value in adult ICU asthma remains unestablished. Systemic inflammatory and catecholaminergic pathways may contribute to myocardial vulnerability. Associations involving allergic inflammation and biologic exposure are hypothesis-generating, and do not demonstrate endotype-specific myocardial injury or cardioprotection. Systemic corticosteroids and biologics require separate consideration of respiratory benefit and cardiovascular effects. Conclusions: Severe asthma can be viewed as an unplanned cardiovascular stress test. Integrated assessment of respiratory mechanics, perfusion, rhythm, congestion, and cardiac function should guide care. Persistent abnormalities warrant reassessment for alternative or coexisting disease rather than an automatic diagnosis of asthma-related cardiomyopathy. 2026-11-12 Diagnostics, Vol. 16, Pages 3746: Beyond Bronchospasm: Cardiovascular Involvement in Severe Asthma

Diagnostics doi: 10.3390/diagnostics16223746

Authors: Javier Hidalgo-Martín María del Carmen Ruiz-Iniesta Beatriz Hidalgo-Martín Ángela Maza-Rodríguez Manuel Ruiz-Bailén

Background: Severe asthma and cardiovascular disease can coexist, mimic one another, and interact through respiratory mechanics and treatment. This narrative review examines these relationships and their implications for intensive care. Main findings: Conventional and tissue Doppler studies identified cardiac abnormalities in asthma before widespread use of speckle tracking in this field. Subsequent deformation studies include predominantly pediatric or non-ICU populations, alongside limited adult acute severe-asthma evidence. Their findings are heterogeneous and largely observational. During exacerbations, dynamic hyperinflation, intrinsic positive end-expiratory pressure, pleural-pressure swings, right-ventricular loading, ventricular interdependence, gas-exchange abnormalities, adrenergic stimulation, and ventilation may alter filling and forward flow without primary cardiomyopathy. Conversely, heart failure with preserved ejection fraction can present with wheezing, but neither B-lines nor an isolated echocardiographic filling index establishes that diagnosis. Four ICU scenarios illustrate low flow despite high ejection fraction, post-intubation shock, congestion with preserved ejection fraction, and arrhythmia with transient dysfunction. Strain may help characterize serial changes but is load dependent; its incremental clinical value in adult ICU asthma remains unestablished. Systemic inflammatory and catecholaminergic pathways may contribute to myocardial vulnerability. Associations involving allergic inflammation and biologic exposure are hypothesis-generating, and do not demonstrate endotype-specific myocardial injury or cardioprotection. Systemic corticosteroids and biologics require separate consideration of respiratory benefit and cardiovascular effects. Conclusions: Severe asthma can be viewed as an unplanned cardiovascular stress test. Integrated assessment of respiratory mechanics, perfusion, rhythm, congestion, and cardiac function should guide care. Persistent abnormalities warrant reassessment for alternative or coexisting disease rather than an automatic diagnosis of asthma-related cardiomyopathy.

]]> Beyond Bronchospasm: Cardiovascular Involvement in Severe Asthma Javier Hidalgo-Martín María del Carmen Ruiz-Iniesta Beatriz Hidalgo-Martín Ángela Maza-Rodríguez Manuel Ruiz-Bailén doi: 10.3390/diagnostics16223746 Diagnostics 2026-11-12 Diagnostics 2026-11-12 16 22 Review 3746 10.3390/diagnostics16223746 https://www.mdpi.com/2075-4418/16/22/3746 Diagnostics, Vol. 16, Pages 3745: Bench Agreement of Two Units of a Low-Cost Digital Manometers with a Clinical Respiratory Pressure Comparator: A Laboratory-Based Comparison https://www.mdpi.com/2075-4418/16/22/3745 Background: Maximal inspiratory (MIP) and expiratory (MEP) pressures are widely used indices of respiratory muscle strength, but clinical manometers are costly. We evaluated the bench agreement of two units of a low-cost digital manometer with a clinical respiratory pressure comparator. Methods: Two BioPimo 101® units and a Vitalograph Pneumotrac 6800® were connected simultaneously to a mechanical insufflation–exsufflation device coupled to a test lung. Pressures of 5–70 cmH2O were applied in 5-cmH2O steps under two compliance conditions, in triplicate (56 conditions; 336 paired differences analyzed as repeated measurements). Agreement was assessed with Bland–Altman analysis, condition-clustered bootstrap confidence intervals, regression-based limits of agreement and ICC (2,1). Results: For MIP, mean differences were −0.03 to 0.21 cmH2O (limits of agreement −0.42 to 0.72 cmH2O). For MEP, both units showed higher readings than the comparator (mean differences 0.52–0.72 cmH2O), and differences increased with pressure; at 70 cmH2O under low compliance, the predicted upper limit of agreement reached 2.44–2.64 cmH2O. ICCs exceeded 0.999. Conclusions: Both units agreed closely with the comparator under bench conditions, particularly for MIP, whereas MEP showed positive, pressure-dependent differences. Without a traceable pressure standard and with only two units tested, these findings do not establish absolute accuracy or clinical interchangeability. 2026-11-12 Diagnostics, Vol. 16, Pages 3745: Bench Agreement of Two Units of a Low-Cost Digital Manometers with a Clinical Respiratory Pressure Comparator: A Laboratory-Based Comparison

Diagnostics doi: 10.3390/diagnostics16223745

Authors: Rodrigo Torres-Castro Matías Otto-Yáñez Claudia Saldaña-Villegas Luis Vasconcello-Castillo Giovanna Binetti Homero Puppo Marisol Barros-Poblete Roberto Vera-Uribe

Background: Maximal inspiratory (MIP) and expiratory (MEP) pressures are widely used indices of respiratory muscle strength, but clinical manometers are costly. We evaluated the bench agreement of two units of a low-cost digital manometer with a clinical respiratory pressure comparator. Methods: Two BioPimo 101® units and a Vitalograph Pneumotrac 6800® were connected simultaneously to a mechanical insufflation–exsufflation device coupled to a test lung. Pressures of 5–70 cmH2O were applied in 5-cmH2O steps under two compliance conditions, in triplicate (56 conditions; 336 paired differences analyzed as repeated measurements). Agreement was assessed with Bland–Altman analysis, condition-clustered bootstrap confidence intervals, regression-based limits of agreement and ICC (2,1). Results: For MIP, mean differences were −0.03 to 0.21 cmH2O (limits of agreement −0.42 to 0.72 cmH2O). For MEP, both units showed higher readings than the comparator (mean differences 0.52–0.72 cmH2O), and differences increased with pressure; at 70 cmH2O under low compliance, the predicted upper limit of agreement reached 2.44–2.64 cmH2O. ICCs exceeded 0.999. Conclusions: Both units agreed closely with the comparator under bench conditions, particularly for MIP, whereas MEP showed positive, pressure-dependent differences. Without a traceable pressure standard and with only two units tested, these findings do not establish absolute accuracy or clinical interchangeability.

]]> Bench Agreement of Two Units of a Low-Cost Digital Manometers with a Clinical Respiratory Pressure Comparator: A Laboratory-Based Comparison Rodrigo Torres-Castro Matías Otto-Yáñez Claudia Saldaña-Villegas Luis Vasconcello-Castillo Giovanna Binetti Homero Puppo Marisol Barros-Poblete Roberto Vera-Uribe doi: 10.3390/diagnostics16223745 Diagnostics 2026-11-12 Diagnostics 2026-11-12 16 22 Article 3745 10.3390/diagnostics16223745 https://www.mdpi.com/2075-4418/16/22/3745 Diagnostics, Vol. 16, Pages 3744: Calprotectin Measurement in Rectal Mucus Collected with the OriCol™ Sampling Device: A Method-Comparison Study Against Faecal Calprotectin Reference Tests https://www.mdpi.com/2075-4418/16/22/3744 Background: Faecal calprotectin is recommended by the UK National Institute of Health and Care Excellence (NICE) HealthTech guidance HTG320 (2013) to distinguish inflammatory bowel disease (IBD) from functional bowel disorders, including irritable bowel syndrome (IBS), when cancer is not suspected, and to monitor IBD activity. Stool collection can limit adherence. Home-based and smartphone-enabled assays partly address this gap, but clinic-acquired sampling could provide results soon after consultation. We compared calprotectin in OriCol™ Sampling Device-collected rectal mucus with matched faecal calprotectin. Methods: Sixty-six adults were prospectively recruited from three NHS gastroenterology clinics. Each provided a clinic-acquired rectal mucus sample and matched stool sample. Calprotectin was measured using two CE-marked ELISAs (IDK® Calprotectin and fCAL®), with laboratory staff blinded to clinical category. The primary endpoint was categorical agreement at the 50 µg/g faecal threshold; secondary analyses included Bland–Altman analysis, Cohen’s κ and patient acceptability. Results: Calprotectin was detected across both assays’ working ranges and correlated positively between matrices. Forty-eight participants were eligible for threshold analysis. Regression-derived rectal mucus equivalents produced positive percent agreement of 79% (95% CI 61–91) for IDK® and 68% (51–82) for fCAL®, and negative percent agreement of 53% (27–79) and 40% (12–74), respectively. Chance-corrected agreement was fair for IDK® (κ 0.32, 95% CI 0.02–0.62) and slight for fCAL® (κ 0.07, 95% CI −0.27–0.41), and Bland–Altman 95% limits of agreement between matrices were wide (spanning roughly two orders of magnitude). Among IBD patients, paired results were above threshold in 93% and 86%, respectively. Of 60 respondents, 96.7% would repeat sampling, 55.6% of those expressing a preference (30 of 54) chose OriCol™, and no OriCol™ Sampling Device-related adverse events occurred. Conclusions: OriCol™ enabled acceptable clinic-based rectal mucus calprotectin measurement with positive correlation to faecal results. Above-threshold agreement was encouraging, but the low negative agreement, the fair-to-slight κ values and the wide between-matrix limits of agreement indicate that rectal mucus calprotectin is not equivalent to faecal calprotectin. Below-threshold agreement, in particular, requires confirmation in larger independent cohorts with pre-specified thresholds before clinical implementation based upon current diagnostic platform threshold. 2026-11-12 Diagnostics, Vol. 16, Pages 3744: Calprotectin Measurement in Rectal Mucus Collected with the OriCol™ Sampling Device: A Method-Comparison Study Against Faecal Calprotectin Reference Tests

Diagnostics doi: 10.3390/diagnostics16223744

Authors: Andrew J. Tock Daniel Wise Ian R. Daniels Andrew J. Page Paul A. Smith Paul Knight John McLaughlin

Background: Faecal calprotectin is recommended by the UK National Institute of Health and Care Excellence (NICE) HealthTech guidance HTG320 (2013) to distinguish inflammatory bowel disease (IBD) from functional bowel disorders, including irritable bowel syndrome (IBS), when cancer is not suspected, and to monitor IBD activity. Stool collection can limit adherence. Home-based and smartphone-enabled assays partly address this gap, but clinic-acquired sampling could provide results soon after consultation. We compared calprotectin in OriCol™ Sampling Device-collected rectal mucus with matched faecal calprotectin. Methods: Sixty-six adults were prospectively recruited from three NHS gastroenterology clinics. Each provided a clinic-acquired rectal mucus sample and matched stool sample. Calprotectin was measured using two CE-marked ELISAs (IDK® Calprotectin and fCAL®), with laboratory staff blinded to clinical category. The primary endpoint was categorical agreement at the 50 µg/g faecal threshold; secondary analyses included Bland–Altman analysis, Cohen’s κ and patient acceptability. Results: Calprotectin was detected across both assays’ working ranges and correlated positively between matrices. Forty-eight participants were eligible for threshold analysis. Regression-derived rectal mucus equivalents produced positive percent agreement of 79% (95% CI 61–91) for IDK® and 68% (51–82) for fCAL®, and negative percent agreement of 53% (27–79) and 40% (12–74), respectively. Chance-corrected agreement was fair for IDK® (κ 0.32, 95% CI 0.02–0.62) and slight for fCAL® (κ 0.07, 95% CI −0.27–0.41), and Bland–Altman 95% limits of agreement between matrices were wide (spanning roughly two orders of magnitude). Among IBD patients, paired results were above threshold in 93% and 86%, respectively. Of 60 respondents, 96.7% would repeat sampling, 55.6% of those expressing a preference (30 of 54) chose OriCol™, and no OriCol™ Sampling Device-related adverse events occurred. Conclusions: OriCol™ enabled acceptable clinic-based rectal mucus calprotectin measurement with positive correlation to faecal results. Above-threshold agreement was encouraging, but the low negative agreement, the fair-to-slight κ values and the wide between-matrix limits of agreement indicate that rectal mucus calprotectin is not equivalent to faecal calprotectin. Below-threshold agreement, in particular, requires confirmation in larger independent cohorts with pre-specified thresholds before clinical implementation based upon current diagnostic platform threshold.

]]> Calprotectin Measurement in Rectal Mucus Collected with the OriCol™ Sampling Device: A Method-Comparison Study Against Faecal Calprotectin Reference Tests Andrew J. Tock Daniel Wise Ian R. Daniels Andrew J. Page Paul A. Smith Paul Knight John McLaughlin doi: 10.3390/diagnostics16223744 Diagnostics 2026-11-12 Diagnostics 2026-11-12 16 22 Article 3744 10.3390/diagnostics16223744 https://www.mdpi.com/2075-4418/16/22/3744 Diagnostics, Vol. 16, Pages 3743: Practical Application of EndoFLIP in the Evaluation of Patients with Dysphagia https://www.mdpi.com/2075-4418/16/22/3743 Dysphagia evaluation traditionally proceeds from a history and upper endoscopy to high-resolution manometry (HRM), the reference standard for esophageal motor assessment; however, HRM is swallow-dependent, technically demanding, and yields inconclusive or discordant findings, particularly esophagogastric junction outflow obstruction (EGJOO) patterns, in a clinically meaningful proportion of studies. Functional lumen imaging probe (FLIP) Panometry was developed to complement HRM by using impedance planimetry to characterize esophagogastric junction (EGJ) opening and distension-induced esophageal body contractility during sedated endoscopy, offering a mechanical rather than purely pressure-based assessment of esophageal motor function. This review synthesizes the technique, standardized interpretive framework, and clinical evidence supporting FLIP Panometry across the dysphagia evaluation pathway. We describe the FLIP protocol and core metrics, the EGJ distensibility index, maximum EGJ diameter, contractile response pattern, and distensibility plateau that together generate a motility classification per the Dallas Consensus. We then detail FLIP’s principal clinical applications: clarifying inconclusive or discordant HRM, particularly EGJOO; providing complementary information at index endoscopy, where integration with endoscopic findings, such as the endoscopic CARS score, can expedite diagnosis and reduce reliance on subsequent HRM; serving as a physiologic outcome measure after achalasia-directed therapy; and characterizing fibrostenotic remodeling in eosinophilic esophagitis through esophageal body distensibility. FLIP’s safety profile, interrater reliability, and key limitations, including reduced sensitivity for spastic motor disorders relative to HRM, are reviewed, alongside emerging directions. Taken together, FLIP Panometry has become an established component of contemporary esophageal evaluation, providing mechanistic information that complements, rather than replaces, endoscopy, histology, barium radiology, and manometry in the comprehensive work-up of dysphagia. 2026-11-12 Diagnostics, Vol. 16, Pages 3743: Practical Application of EndoFLIP in the Evaluation of Patients with Dysphagia

Diagnostics doi: 10.3390/diagnostics16223743

Authors: Chloe Savino Dustin A. Carlson

Dysphagia evaluation traditionally proceeds from a history and upper endoscopy to high-resolution manometry (HRM), the reference standard for esophageal motor assessment; however, HRM is swallow-dependent, technically demanding, and yields inconclusive or discordant findings, particularly esophagogastric junction outflow obstruction (EGJOO) patterns, in a clinically meaningful proportion of studies. Functional lumen imaging probe (FLIP) Panometry was developed to complement HRM by using impedance planimetry to characterize esophagogastric junction (EGJ) opening and distension-induced esophageal body contractility during sedated endoscopy, offering a mechanical rather than purely pressure-based assessment of esophageal motor function. This review synthesizes the technique, standardized interpretive framework, and clinical evidence supporting FLIP Panometry across the dysphagia evaluation pathway. We describe the FLIP protocol and core metrics, the EGJ distensibility index, maximum EGJ diameter, contractile response pattern, and distensibility plateau that together generate a motility classification per the Dallas Consensus. We then detail FLIP’s principal clinical applications: clarifying inconclusive or discordant HRM, particularly EGJOO; providing complementary information at index endoscopy, where integration with endoscopic findings, such as the endoscopic CARS score, can expedite diagnosis and reduce reliance on subsequent HRM; serving as a physiologic outcome measure after achalasia-directed therapy; and characterizing fibrostenotic remodeling in eosinophilic esophagitis through esophageal body distensibility. FLIP’s safety profile, interrater reliability, and key limitations, including reduced sensitivity for spastic motor disorders relative to HRM, are reviewed, alongside emerging directions. Taken together, FLIP Panometry has become an established component of contemporary esophageal evaluation, providing mechanistic information that complements, rather than replaces, endoscopy, histology, barium radiology, and manometry in the comprehensive work-up of dysphagia.

]]> Practical Application of EndoFLIP in the Evaluation of Patients with Dysphagia Chloe Savino Dustin A. Carlson doi: 10.3390/diagnostics16223743 Diagnostics 2026-11-12 Diagnostics 2026-11-12 16 22 Review 3743 10.3390/diagnostics16223743 https://www.mdpi.com/2075-4418/16/22/3743 Diagnostics, Vol. 16, Pages 3742: Preterm Small-for-Gestational-Age Risk Estimates Using Large Language Models Versus the FMF Competing-Risks Model https://www.mdpi.com/2075-4418/16/22/3742 Introduction: The midgestation prediction of preterm small-for-gestational-age (SGA) birth could use the externally validated Fetal Medicine Foundation (FMF) competing-risks model, integrating maternal characteristics and obstetric history with fetal biometry and biophysical markers. Large language model (LLM) systems are increasingly used for pregnancy-related health information, but how their numerical risk estimates respond to clinical inputs compared with this model is not known. Objective: To compare the direction and relative magnitude of changes in numerical estimates of preterm SGA risk from eight LLMs and the FMF competing-risks model when individual predictors are varied, and examine how agreement relates to the calculation methods reported by the LLMs. Methods: We generated 108 synthetic singleton pregnancy scenarios by varying one of 16 clinical variables (19 encoded predictors) at a time around low-risk multiparous and nulliparous profiles assessed at 22 weeks. Each LLM was queried once through its consumer interface for the probability of birthweight below the 10th percentile with delivery before 37 weeks; temperature and tool use could not be controlled. FMF probabilities were calculated from the published equations. Local interpretable model-agnostic explanation (LIME)-inspired weighted linear surrogates were fitted to logit-transformed probabilities and compared with FMF using an exploratory composite alignment score, combining directional concordance, Spearman correlation, cosine similarity, and normalized root mean squared error similarity. Absolute agreement was assessed on the logit scale. Results: The largest FMF surrogate coefficients were chronic hypertension, diabetes mellitus, and smoking among binary predictors, and uterine artery pulsatility index, estimated fetal weight Z-score, and gestational age at the previous delivery among continuous predictors. Composite alignment with FMF was highest for GPT-6 (0.999), Mistral (0.988), and Grok (0.917), followed by Claude (0.894), DeepSeek (0.769), Meta (0.752), Qwen (0.600), and Copilot (0.492). Diabetes mellitus received a negative surrogate coefficient in four LLMs, although only DeepSeek returned a lower probability with diabetes than without. Predicted probabilities agreed closely with FMF only for GPT-6; the other LLMs predicted higher risks, with odds on average 1.2 to 9 times those of FMF. GPT-6, Mistral, and Grok reported implementing the published FMF algorithm, although this cannot be verified; Claude, DeepSeek, and Qwen described approximate logistic models; and Copilot and Meta displayed no process messages. Conclusions: Under a single prompt and uncontrolled consumer access conditions, similarity to the FMF model varied widely and was highest for LLMs reporting use of the published algorithm, while predicted risks often diverged, even when the effects of individual risk factors were similar. Verification of the calculations and validation against observed pregnancy outcomes are required before clinical application. 2026-11-12 Diagnostics, Vol. 16, Pages 3742: Preterm Small-for-Gestational-Age Risk Estimates Using Large Language Models Versus the FMF Competing-Risks Model

Diagnostics doi: 10.3390/diagnostics16223742

Authors: Denisa O. Zelinschi Oriana M. Onicescu Alexandra Ursache Eduard Cristian Mihoci Sorana Anton Emil Anton Dragos Nemescu

Introduction: The midgestation prediction of preterm small-for-gestational-age (SGA) birth could use the externally validated Fetal Medicine Foundation (FMF) competing-risks model, integrating maternal characteristics and obstetric history with fetal biometry and biophysical markers. Large language model (LLM) systems are increasingly used for pregnancy-related health information, but how their numerical risk estimates respond to clinical inputs compared with this model is not known. Objective: To compare the direction and relative magnitude of changes in numerical estimates of preterm SGA risk from eight LLMs and the FMF competing-risks model when individual predictors are varied, and examine how agreement relates to the calculation methods reported by the LLMs. Methods: We generated 108 synthetic singleton pregnancy scenarios by varying one of 16 clinical variables (19 encoded predictors) at a time around low-risk multiparous and nulliparous profiles assessed at 22 weeks. Each LLM was queried once through its consumer interface for the probability of birthweight below the 10th percentile with delivery before 37 weeks; temperature and tool use could not be controlled. FMF probabilities were calculated from the published equations. Local interpretable model-agnostic explanation (LIME)-inspired weighted linear surrogates were fitted to logit-transformed probabilities and compared with FMF using an exploratory composite alignment score, combining directional concordance, Spearman correlation, cosine similarity, and normalized root mean squared error similarity. Absolute agreement was assessed on the logit scale. Results: The largest FMF surrogate coefficients were chronic hypertension, diabetes mellitus, and smoking among binary predictors, and uterine artery pulsatility index, estimated fetal weight Z-score, and gestational age at the previous delivery among continuous predictors. Composite alignment with FMF was highest for GPT-6 (0.999), Mistral (0.988), and Grok (0.917), followed by Claude (0.894), DeepSeek (0.769), Meta (0.752), Qwen (0.600), and Copilot (0.492). Diabetes mellitus received a negative surrogate coefficient in four LLMs, although only DeepSeek returned a lower probability with diabetes than without. Predicted probabilities agreed closely with FMF only for GPT-6; the other LLMs predicted higher risks, with odds on average 1.2 to 9 times those of FMF. GPT-6, Mistral, and Grok reported implementing the published FMF algorithm, although this cannot be verified; Claude, DeepSeek, and Qwen described approximate logistic models; and Copilot and Meta displayed no process messages. Conclusions: Under a single prompt and uncontrolled consumer access conditions, similarity to the FMF model varied widely and was highest for LLMs reporting use of the published algorithm, while predicted risks often diverged, even when the effects of individual risk factors were similar. Verification of the calculations and validation against observed pregnancy outcomes are required before clinical application.

]]> Preterm Small-for-Gestational-Age Risk Estimates Using Large Language Models Versus the FMF Competing-Risks Model Denisa O. Zelinschi Oriana M. Onicescu Alexandra Ursache Eduard Cristian Mihoci Sorana Anton Emil Anton Dragos Nemescu doi: 10.3390/diagnostics16223742 Diagnostics 2026-11-12 Diagnostics 2026-11-12 16 22 Article 3742 10.3390/diagnostics16223742 https://www.mdpi.com/2075-4418/16/22/3742 Diagnostics, Vol. 16, Pages 3741: Cadaveric Research for Understanding Mechanisms and Advancing Diagnosis and Treatment of Osteoarthritis: A Systematic Review https://www.mdpi.com/2075-4418/16/22/3741 Background/Objectives: Osteoarthritis (OA) mechanisms are extensively investigated to enable the development of improved diagnostics and therapeutic strategies. Cadaveric tissues are frequently used as “healthy” comparators in mechanistic studies and as laboratory models for the development of new surgical techniques and biomechanical studies. In parallel, advanced cell-based therapies for OA are emerging; however, their usage remains limited, particularly because of the restricted availability and variability of living donor tissues. This review evaluates the contribution of cadaveric tissues to our understanding of OA pathogenesis, diagnosis, and treatment development. Methods: A PRISMA-compliant literature search was conducted in PubMed, Web of Science, and Scopus. Studies involving cadaveric human tissues in OA research were included; animal studies, reviews, and clinical studies without cadaveric samples were excluded. Results: A total of 120 records were identified, of which 52 met the inclusion criteria. Most studies (n = 22) used cadaveric tissues to investigate mechanisms of joint degeneration and OA pathophysiology. The remaining studies were distributed between the development or optimization of diagnostic techniques (n = 9) and orthopedic or related therapeutic approaches (n = 21). Studies exploring cellular therapies derived from cadaveric tissues were scarce and were predominantly identified through citation tracking and reference list screening. Conclusions: Cadaveric studies have contributed to OA research, particularly in the elucidation of its mechanisms. Their potential in the development of cadaveric-derived cellular therapies for regenerative medicine is still in a preliminary phase of development and analysis. Future research should prioritize standardization and optimization of such approaches for eventual clinical applications. 2026-11-12 Diagnostics, Vol. 16, Pages 3741: Cadaveric Research for Understanding Mechanisms and Advancing Diagnosis and Treatment of Osteoarthritis: A Systematic Review

Diagnostics doi: 10.3390/diagnostics16223741

Authors: Janja Zupan Gregor Haring

Background/Objectives: Osteoarthritis (OA) mechanisms are extensively investigated to enable the development of improved diagnostics and therapeutic strategies. Cadaveric tissues are frequently used as “healthy” comparators in mechanistic studies and as laboratory models for the development of new surgical techniques and biomechanical studies. In parallel, advanced cell-based therapies for OA are emerging; however, their usage remains limited, particularly because of the restricted availability and variability of living donor tissues. This review evaluates the contribution of cadaveric tissues to our understanding of OA pathogenesis, diagnosis, and treatment development. Methods: A PRISMA-compliant literature search was conducted in PubMed, Web of Science, and Scopus. Studies involving cadaveric human tissues in OA research were included; animal studies, reviews, and clinical studies without cadaveric samples were excluded. Results: A total of 120 records were identified, of which 52 met the inclusion criteria. Most studies (n = 22) used cadaveric tissues to investigate mechanisms of joint degeneration and OA pathophysiology. The remaining studies were distributed between the development or optimization of diagnostic techniques (n = 9) and orthopedic or related therapeutic approaches (n = 21). Studies exploring cellular therapies derived from cadaveric tissues were scarce and were predominantly identified through citation tracking and reference list screening. Conclusions: Cadaveric studies have contributed to OA research, particularly in the elucidation of its mechanisms. Their potential in the development of cadaveric-derived cellular therapies for regenerative medicine is still in a preliminary phase of development and analysis. Future research should prioritize standardization and optimization of such approaches for eventual clinical applications.

]]> Cadaveric Research for Understanding Mechanisms and Advancing Diagnosis and Treatment of Osteoarthritis: A Systematic Review Janja Zupan Gregor Haring doi: 10.3390/diagnostics16223741 Diagnostics 2026-11-12 Diagnostics 2026-11-12 16 22 Systematic Review 3741 10.3390/diagnostics16223741 https://www.mdpi.com/2075-4418/16/22/3741 Diagnostics, Vol. 16, Pages 3740: Preoperative Assessment of Solid Pancreatic Lesions Associated with Chronic Pancreatitis https://www.mdpi.com/2075-4418/16/22/3740 Distinguishing solid pancreatic lesions arising in the background of chronic pancreatitis represents an important diagnostic challenge because mass-forming inflammatory lesions and pancreatic cancer share overlapping clinical, serological, and radiological features and their discrimination might delay the curative treatment. The features of chronic pancreatitis such as fibrosis, calcifications with acoustic shadowing, parenchymal atrophy, and main pancreatic duct abnormalities, may either mimic pancreatic ductal adenocarcinoma or obscure small malignant lesions, thereby limiting the performance of conventional imaging modalities. Surveillance for pancreatic cancer in chronic pancreatitis is recommended only for selected high-risk patients with hereditary pancreatitis; however, in patients with non-hereditary chronic pancreatitis, clinical vigilance for red flags (new-onset diabetes, weight loss, jaundice, rising CA19-9) should prompt urgent imaging diagnosis and tissue acquisition. This review summarizes the current evidence on the diagnostic preoperative assessment of solid pancreatic lesions in chronic pancreatitis, highlighting the roles of computed tomography, magnetic resonance imaging, endoscopic ultrasound, and histopathological assessment. Endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) has become the preferred method for tissue diagnosis because of its superior ability to obtain histological core specimens, although the tumors may present low cellularity and the correct targeting is often difficult. False-negative results, or misinterpretation of well-differentiated carcinoma as a benign condition remain real concerns because they delay the appropriate treatment. For these reasons a non-diagnostic biopsy should be interpreted cautiously by a multidisciplinary team especially when the suspicion for cancer is high. 2026-11-12 Diagnostics, Vol. 16, Pages 3740: Preoperative Assessment of Solid Pancreatic Lesions Associated with Chronic Pancreatitis

Diagnostics doi: 10.3390/diagnostics16223740

Authors: Edina-Cristina Seulean Radu Seicean Cristina Pojoga Andrada Seicean

Distinguishing solid pancreatic lesions arising in the background of chronic pancreatitis represents an important diagnostic challenge because mass-forming inflammatory lesions and pancreatic cancer share overlapping clinical, serological, and radiological features and their discrimination might delay the curative treatment. The features of chronic pancreatitis such as fibrosis, calcifications with acoustic shadowing, parenchymal atrophy, and main pancreatic duct abnormalities, may either mimic pancreatic ductal adenocarcinoma or obscure small malignant lesions, thereby limiting the performance of conventional imaging modalities. Surveillance for pancreatic cancer in chronic pancreatitis is recommended only for selected high-risk patients with hereditary pancreatitis; however, in patients with non-hereditary chronic pancreatitis, clinical vigilance for red flags (new-onset diabetes, weight loss, jaundice, rising CA19-9) should prompt urgent imaging diagnosis and tissue acquisition. This review summarizes the current evidence on the diagnostic preoperative assessment of solid pancreatic lesions in chronic pancreatitis, highlighting the roles of computed tomography, magnetic resonance imaging, endoscopic ultrasound, and histopathological assessment. Endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) has become the preferred method for tissue diagnosis because of its superior ability to obtain histological core specimens, although the tumors may present low cellularity and the correct targeting is often difficult. False-negative results, or misinterpretation of well-differentiated carcinoma as a benign condition remain real concerns because they delay the appropriate treatment. For these reasons a non-diagnostic biopsy should be interpreted cautiously by a multidisciplinary team especially when the suspicion for cancer is high.

]]> Preoperative Assessment of Solid Pancreatic Lesions Associated with Chronic Pancreatitis Edina-Cristina Seulean Radu Seicean Cristina Pojoga Andrada Seicean doi: 10.3390/diagnostics16223740 Diagnostics 2026-11-12 Diagnostics 2026-11-12 16 22 Review 3740 10.3390/diagnostics16223740 https://www.mdpi.com/2075-4418/16/22/3740 Diagnostics, Vol. 16, Pages 3739: Microscopic Fat on Chemical-Shift MRI in Solid Renal Tumours: Clear Cell Carcinoma, Fat-Poor Angiomyolipoma and the Added Value of T2-Weighted Heterogeneity and Necrosis https://www.mdpi.com/2075-4418/16/22/3739 Background/Objectives: To assess whether microscopic fat on chemical-shift MRI, T2-weighted heterogeneity and necrosis separate clear cell renal cell carcinoma (ccRCC) and fat-poor angiomyolipoma (AML) from other solid renal tumours and from each other. Methods: Seventy pathologically proven solid renal tumours without macroscopic fat (38 ccRCCs, 17 papillary RCCs, five chromophobe RCCs, six AMLs, and four oncocytomas) consecutively imaged at 1.5 T between 2017 and 2021 were reviewed retrospectively by one radiologist blinded to histology. Visual signal loss, the chemical-shift index (CSI) and a tumour-to-kidney signal-intensity drop ratio were recorded; signal loss > 20% defined microscopic fat. T2-weighted heterogeneity and necrosis/cystic degeneration (T2-weighted and contrast-enhanced T1-weighted images) were recorded. Groups were compared with non-parametric and Fisher’s exact tests. Results: Median CSI was 43.8% in AML, 14.3% in ccRCC and ≤11.7% in the other subtypes (p < 0.001). A CSI > 20% was observed in 20 of 44 ccRCCs or AMLs and in 1 of 26 other tumours (p < 0.001; sensitivity 45.5%, specificity 96.2%); the tumour-to-kidney ratio and visual assessment performed similarly. AML had higher CSI than ccRCC (p = 0.033), but threshold positivity did not differ significantly (5/6 vs. 15/38; p = 0.077). T2-weighted heterogeneity (84% vs. 17%; p = 0.002) and necrosis/cystic degeneration (82% vs. 0%; p < 0.001) were more frequent in ccRCC than AML. An exploratory AML-positive criterion combining CSI > 20% with T2 homogeneity increased specificity from 60.5% to 92.1%, while sensitivity decreased from 83.3% to 66.7%. A negative CSI was more frequent in papillary RCC (59% vs. 19%, p = 0.004). Conclusions: Opposed-phase signal loss > 20% is a specific but insensitive marker of ccRCC or AML. Morphology provided exploratory complementary information, but the six-AML subgroup limits precision. 2026-11-12 Diagnostics, Vol. 16, Pages 3739: Microscopic Fat on Chemical-Shift MRI in Solid Renal Tumours: Clear Cell Carcinoma, Fat-Poor Angiomyolipoma and the Added Value of T2-Weighted Heterogeneity and Necrosis

Diagnostics doi: 10.3390/diagnostics16223739

Authors: Ferhat Çengel Özgür Genç

Background/Objectives: To assess whether microscopic fat on chemical-shift MRI, T2-weighted heterogeneity and necrosis separate clear cell renal cell carcinoma (ccRCC) and fat-poor angiomyolipoma (AML) from other solid renal tumours and from each other. Methods: Seventy pathologically proven solid renal tumours without macroscopic fat (38 ccRCCs, 17 papillary RCCs, five chromophobe RCCs, six AMLs, and four oncocytomas) consecutively imaged at 1.5 T between 2017 and 2021 were reviewed retrospectively by one radiologist blinded to histology. Visual signal loss, the chemical-shift index (CSI) and a tumour-to-kidney signal-intensity drop ratio were recorded; signal loss > 20% defined microscopic fat. T2-weighted heterogeneity and necrosis/cystic degeneration (T2-weighted and contrast-enhanced T1-weighted images) were recorded. Groups were compared with non-parametric and Fisher’s exact tests. Results: Median CSI was 43.8% in AML, 14.3% in ccRCC and ≤11.7% in the other subtypes (p < 0.001). A CSI > 20% was observed in 20 of 44 ccRCCs or AMLs and in 1 of 26 other tumours (p < 0.001; sensitivity 45.5%, specificity 96.2%); the tumour-to-kidney ratio and visual assessment performed similarly. AML had higher CSI than ccRCC (p = 0.033), but threshold positivity did not differ significantly (5/6 vs. 15/38; p = 0.077). T2-weighted heterogeneity (84% vs. 17%; p = 0.002) and necrosis/cystic degeneration (82% vs. 0%; p < 0.001) were more frequent in ccRCC than AML. An exploratory AML-positive criterion combining CSI > 20% with T2 homogeneity increased specificity from 60.5% to 92.1%, while sensitivity decreased from 83.3% to 66.7%. A negative CSI was more frequent in papillary RCC (59% vs. 19%, p = 0.004). Conclusions: Opposed-phase signal loss > 20% is a specific but insensitive marker of ccRCC or AML. Morphology provided exploratory complementary information, but the six-AML subgroup limits precision.

]]> Microscopic Fat on Chemical-Shift MRI in Solid Renal Tumours: Clear Cell Carcinoma, Fat-Poor Angiomyolipoma and the Added Value of T2-Weighted Heterogeneity and Necrosis Ferhat Çengel Özgür Genç doi: 10.3390/diagnostics16223739 Diagnostics 2026-11-12 Diagnostics 2026-11-12 16 22 Article 3739 10.3390/diagnostics16223739 https://www.mdpi.com/2075-4418/16/22/3739 Diagnostics, Vol. 16, Pages 3738: PulmonaryAspergilloma Developing in a Giant Emphysematous Bulla https://www.mdpi.com/2075-4418/16/22/3738 Pulmonary aspergilloma usually develops in a pre-existing pulmonary cavity and may present with hemoptysis. We report a 51-year-old former smoker with bilateral apical post-tuberculous sequelae, severe chronic obstructive pulmonary disease, chronic respiratory failure requiring long-term oxygen therapy, and a three-month history of worsening dyspnea, productive cough with intermittent mild hemoptysis (blood-streaked sputum), and right-sided pleuritic pain. Chest computed tomography demonstrated bilateral giant emphysematous bullae and a round intracavitary soft-tissue mass within a right upper-lobe cavity of uncertain origin, partially outlined by a crescent of air. Bronchoscopy showed marked traction-related bronchial distortion without an endobronchial lesion. Bronchial aspirate was positive for Aspergillus spp. by polymerase chain reaction and fungal culture, while investigations for active tuberculosis were negative. Surgical resection was considered unsuitable because of severely impaired pulmonary function and extensive parenchymal destruction. Itraconazole was initiated; during approximately eight months of therapy, two admissions for mild hemoptysis were followed by resolution, and the patient was otherwise reported to be clinically stable; no follow-up data were available after this period. This case illustrates an uncommon site of aspergilloma formation and emphasizes the diagnostic value of correlating characteristic imaging findings with microbiological results in patients with advanced structural lung disease. 2026-11-12 Diagnostics, Vol. 16, Pages 3738: PulmonaryAspergilloma Developing in a Giant Emphysematous Bulla

Diagnostics doi: 10.3390/diagnostics16223738

Authors: Ioana Savaniu Ramona-Elena Nedelcu Aida-Andreea Fănică Marina Enache Andrei Cristian Bobocea Nicoleta Vârtejaru Florin-Dumitru Mihălțan

Pulmonary aspergilloma usually develops in a pre-existing pulmonary cavity and may present with hemoptysis. We report a 51-year-old former smoker with bilateral apical post-tuberculous sequelae, severe chronic obstructive pulmonary disease, chronic respiratory failure requiring long-term oxygen therapy, and a three-month history of worsening dyspnea, productive cough with intermittent mild hemoptysis (blood-streaked sputum), and right-sided pleuritic pain. Chest computed tomography demonstrated bilateral giant emphysematous bullae and a round intracavitary soft-tissue mass within a right upper-lobe cavity of uncertain origin, partially outlined by a crescent of air. Bronchoscopy showed marked traction-related bronchial distortion without an endobronchial lesion. Bronchial aspirate was positive for Aspergillus spp. by polymerase chain reaction and fungal culture, while investigations for active tuberculosis were negative. Surgical resection was considered unsuitable because of severely impaired pulmonary function and extensive parenchymal destruction. Itraconazole was initiated; during approximately eight months of therapy, two admissions for mild hemoptysis were followed by resolution, and the patient was otherwise reported to be clinically stable; no follow-up data were available after this period. This case illustrates an uncommon site of aspergilloma formation and emphasizes the diagnostic value of correlating characteristic imaging findings with microbiological results in patients with advanced structural lung disease.

]]> PulmonaryAspergilloma Developing in a Giant Emphysematous Bulla Ioana Savaniu Ramona-Elena Nedelcu Aida-Andreea Fănică Marina Enache Andrei Cristian Bobocea Nicoleta Vârtejaru Florin-Dumitru Mihălțan doi: 10.3390/diagnostics16223738 Diagnostics 2026-11-12 Diagnostics 2026-11-12 16 22 Interesting Images 3738 10.3390/diagnostics16223738 https://www.mdpi.com/2075-4418/16/22/3738 Diagnostics, Vol. 16, Pages 3737: Diagnostic Spectrum and Temporal Trends of Necrotic and Inflammatory Jawbone Lesions: A 22-Year Retrospective Study https://www.mdpi.com/2075-4418/16/22/3737 Background/Objectives: Medication-related osteonecrosis of the jaw (MRONJ), osteoradionecrosis (ORN), and osteomyelitis exhibit overlapping histopathological features, making clinical context essential for etiological differentiation. This study aimed to evaluate the clinicopathological characteristics and temporal distribution of four diagnostic categories of necrotic and inflammatory jawbone lesions over a 22-year period. Methods: This retrospective, single-center study reviewed 25,133 oral and maxillofacial pathology reports from 2004 to 2025. A total of 650 patients were included and categorized using clinicopathological diagnoses and available medication history. Demographic, clinical, anatomical, and temporal characteristics were analyzed, and multivariable logistic regression was performed to identify factors associated with MRONJ. Results: MRONJ was the most frequent diagnosis (51.5%), followed by osteomyelitis (39.2%), ORN (4.9%), and sclerosing osteomyelitis (4.3%). The proportion of MRONJ increased from 24.7% in 2004–2010 to 61.7% in 2018–2025, whereas osteomyelitis declined from 58.1% to 30.0% (p < 0.001). Calendar year was associated with MRONJ classification in the linear regression model (adjusted odds ratio = 1.114; 95% CI: 1.079–1.149; p < 0.001), although sensitivity analyses indicated a nonlinear temporal association. Among MRONJ patients with documented underlying disease, 37.5% had osteoporosis. The number of recorded osteoporosis-associated MRONJ cases increased from 3 in 2004–2010 to 75 in 2018–2025. Conclusions: The distribution of recorded clinicopathological diagnoses of jawbone lesions has shifted substantially, with MRONJ becoming increasingly prominent, including among patients treated for osteoporosis. These findings highlight the importance of integrating biopsy findings with clinical history and medication exposure for etiological differentiation. Changes in diagnostic recognition, terminology, referral patterns, and biopsy practices may have influenced these trends, which do not establish changes in disease incidence. 2026-11-12 Diagnostics, Vol. 16, Pages 3737: Diagnostic Spectrum and Temporal Trends of Necrotic and Inflammatory Jawbone Lesions: A 22-Year Retrospective Study

Diagnostics doi: 10.3390/diagnostics16223737

Authors: Nihan Aksakalli Zeynep Afra Akbiyik Az Envercan Gozuacik Alp Saruhanoglu

Background/Objectives: Medication-related osteonecrosis of the jaw (MRONJ), osteoradionecrosis (ORN), and osteomyelitis exhibit overlapping histopathological features, making clinical context essential for etiological differentiation. This study aimed to evaluate the clinicopathological characteristics and temporal distribution of four diagnostic categories of necrotic and inflammatory jawbone lesions over a 22-year period. Methods: This retrospective, single-center study reviewed 25,133 oral and maxillofacial pathology reports from 2004 to 2025. A total of 650 patients were included and categorized using clinicopathological diagnoses and available medication history. Demographic, clinical, anatomical, and temporal characteristics were analyzed, and multivariable logistic regression was performed to identify factors associated with MRONJ. Results: MRONJ was the most frequent diagnosis (51.5%), followed by osteomyelitis (39.2%), ORN (4.9%), and sclerosing osteomyelitis (4.3%). The proportion of MRONJ increased from 24.7% in 2004–2010 to 61.7% in 2018–2025, whereas osteomyelitis declined from 58.1% to 30.0% (p < 0.001). Calendar year was associated with MRONJ classification in the linear regression model (adjusted odds ratio = 1.114; 95% CI: 1.079–1.149; p < 0.001), although sensitivity analyses indicated a nonlinear temporal association. Among MRONJ patients with documented underlying disease, 37.5% had osteoporosis. The number of recorded osteoporosis-associated MRONJ cases increased from 3 in 2004–2010 to 75 in 2018–2025. Conclusions: The distribution of recorded clinicopathological diagnoses of jawbone lesions has shifted substantially, with MRONJ becoming increasingly prominent, including among patients treated for osteoporosis. These findings highlight the importance of integrating biopsy findings with clinical history and medication exposure for etiological differentiation. Changes in diagnostic recognition, terminology, referral patterns, and biopsy practices may have influenced these trends, which do not establish changes in disease incidence.

]]> Diagnostic Spectrum and Temporal Trends of Necrotic and Inflammatory Jawbone Lesions: A 22-Year Retrospective Study Nihan Aksakalli Zeynep Afra Akbiyik Az Envercan Gozuacik Alp Saruhanoglu doi: 10.3390/diagnostics16223737 Diagnostics 2026-11-12 Diagnostics 2026-11-12 16 22 Article 3737 10.3390/diagnostics16223737 https://www.mdpi.com/2075-4418/16/22/3737 Diagnostics, Vol. 16, Pages 3736: Incremental Value of Systematic Biopsy in Patients with Prostate Imaging Reporting and Data System 5 Lesions Undergoing MRI–Ultrasound Fusion Biopsy: A Single-Operator Study in a Secondary-Care Setting https://www.mdpi.com/2075-4418/16/22/3736 Background/Objectives: This study aimed to evaluate the incremental value of systematic biopsy (SB) in addition to targeted biopsy (TB) and its impact on Grade Group (GG) reclassification in patients with Prostate Imaging Reporting and Data System (PI-RADS) 5 lesions. Methods: We retrospectively reviewed data from 32 patients with PI-RADS 5-only lesions who underwent magnetic resonance imaging–ultrasound fusion transrectal biopsy by a single operator. Based on the patient-level maximum GG, we evaluated the detection of any prostate cancer (GG ≥ 1), clinically significant prostate cancer (GG ≥ 2), and high-grade prostate cancer (GG ≥ 3). An exploratory subgroup analysis was performed according to prostate-specific antigen density (PSAD; <0.15 vs. ≥0.15 ng/mL/mL). Results: Any prostate cancer was detected in 24 patients (75.0%) using TB, with no incremental detection using SB (0.0%; 95% confidence interval [CI], 0.0–10.9). Clinically significant prostate cancer was detected in 21 patients (65.6%) using TB, with incremental detection using SB in one patient (3.1%; 95% CI, 0.1–16.2). High-grade prostate cancer was detected in 17 patients (53.1%) using TB, with incremental detection using SB in one patient (3.1%; 95% CI, 0.1–16.2). The maximum GG was higher in three patients (9.4%) when TB and SB were combined. Among the 20 patients with PSAD ≥ 0.15 ng/mL/mL, no incremental detection of clinically significant prostate cancer or high-grade prostate cancer was observed using SB (0.0%; 95% CI, 0.0–16.8). Conclusions: In this cohort of patients with PI-RADS 5 lesions, the incremental value of SB for cancer detection was limited, although the upper limit of the 95% CI for incremental detection of clinically significant prostate cancer was 16.2%. Nevertheless, SB provided additional grading information in a small number of patients. Larger studies are needed to evaluate the clinical value of selective SB omission in patients with PI-RADS 5 lesions. 2026-11-12 Diagnostics, Vol. 16, Pages 3736: Incremental Value of Systematic Biopsy in Patients with Prostate Imaging Reporting and Data System 5 Lesions Undergoing MRI–Ultrasound Fusion Biopsy: A Single-Operator Study in a Secondary-Care Setting

Diagnostics doi: 10.3390/diagnostics16223736

Authors: Hyun Sik Yoon Jungbum Bae Hyung Suk Kim Hae Won Lee

Background/Objectives: This study aimed to evaluate the incremental value of systematic biopsy (SB) in addition to targeted biopsy (TB) and its impact on Grade Group (GG) reclassification in patients with Prostate Imaging Reporting and Data System (PI-RADS) 5 lesions. Methods: We retrospectively reviewed data from 32 patients with PI-RADS 5-only lesions who underwent magnetic resonance imaging–ultrasound fusion transrectal biopsy by a single operator. Based on the patient-level maximum GG, we evaluated the detection of any prostate cancer (GG ≥ 1), clinically significant prostate cancer (GG ≥ 2), and high-grade prostate cancer (GG ≥ 3). An exploratory subgroup analysis was performed according to prostate-specific antigen density (PSAD; <0.15 vs. ≥0.15 ng/mL/mL). Results: Any prostate cancer was detected in 24 patients (75.0%) using TB, with no incremental detection using SB (0.0%; 95% confidence interval [CI], 0.0–10.9). Clinically significant prostate cancer was detected in 21 patients (65.6%) using TB, with incremental detection using SB in one patient (3.1%; 95% CI, 0.1–16.2). High-grade prostate cancer was detected in 17 patients (53.1%) using TB, with incremental detection using SB in one patient (3.1%; 95% CI, 0.1–16.2). The maximum GG was higher in three patients (9.4%) when TB and SB were combined. Among the 20 patients with PSAD ≥ 0.15 ng/mL/mL, no incremental detection of clinically significant prostate cancer or high-grade prostate cancer was observed using SB (0.0%; 95% CI, 0.0–16.8). Conclusions: In this cohort of patients with PI-RADS 5 lesions, the incremental value of SB for cancer detection was limited, although the upper limit of the 95% CI for incremental detection of clinically significant prostate cancer was 16.2%. Nevertheless, SB provided additional grading information in a small number of patients. Larger studies are needed to evaluate the clinical value of selective SB omission in patients with PI-RADS 5 lesions.

]]> Incremental Value of Systematic Biopsy in Patients with Prostate Imaging Reporting and Data System 5 Lesions Undergoing MRI–Ultrasound Fusion Biopsy: A Single-Operator Study in a Secondary-Care Setting Hyun Sik Yoon Jungbum Bae Hyung Suk Kim Hae Won Lee doi: 10.3390/diagnostics16223736 Diagnostics 2026-11-12 Diagnostics 2026-11-12 16 22 Article 3736 10.3390/diagnostics16223736 https://www.mdpi.com/2075-4418/16/22/3736 Diagnostics, Vol. 16, Pages 3735: TriHG-XAI: A Human-Grounded Framework for Triangulated Explainability Evaluation in Ordinal Clock Drawing Test Quality Prediction https://www.mdpi.com/2075-4418/16/22/3735 Background/Objectives: Deep learning models can score the Clock Drawing Test (CDT) accurately, but their explanations are usually judged by looking at saliency maps. We asked whether complementary quantitative explainability criteria, evaluated against independent human annotations, give convergent evidence that a CDT model has learned interpretable drawing abnormalities. Methods: An image-only ResNet50 was trained to predict five-level CDT scores from the National Health and Aging Trends Study (7708 observations; participant-level split). In 200 separate, participant-unique drawings annotated for seven abnormalities, we evaluated Grad-CAM attribution alignment, matched-ink perturbation sensitivity, and linear probing of frozen representations. Sensitivity analyses covered region-of-interest definitions, data quality, and adjustment for CDT score. Results: On 1181 test observations, the quadratic weighted kappa was 0.740 and accuracy 0.678. Unadjusted analyses suggested abnormality-specific effects, including reduced hand-region attribution for missing or incorrect hands (q < 0.001) and significant perturbation sensitivity for three abnormalities. However, perturbation effects were as large in drawings without the abnormality. Within score levels, neither attribution nor perturbation sensitivity distinguished drawings with and without abnormalities. Within-score linear decodability remained for five abnormalities (AUROC 0.64–0.93), but not for uneven number spacing or same-length hands. Inter-rater agreement varied (κ 0.27–0.85). Conclusions: In this model and dataset, attribution and perturbation sensitivity mainly reflected overall drawing quality and the presence of intact hands and numerals. Abnormality-specific information was detectable only in the learned representation. Feature-level explainability evaluations should control for the prediction target, and saliency maps alone do not show that a model has learned interpretable abnormalities. 2026-11-11 Diagnostics, Vol. 16, Pages 3735: TriHG-XAI: A Human-Grounded Framework for Triangulated Explainability Evaluation in Ordinal Clock Drawing Test Quality Prediction

Diagnostics doi: 10.3390/diagnostics16223735

Authors: Ayat Elmyerigiy Emad Sami Jaha Alaa Bafail

Background/Objectives: Deep learning models can score the Clock Drawing Test (CDT) accurately, but their explanations are usually judged by looking at saliency maps. We asked whether complementary quantitative explainability criteria, evaluated against independent human annotations, give convergent evidence that a CDT model has learned interpretable drawing abnormalities. Methods: An image-only ResNet50 was trained to predict five-level CDT scores from the National Health and Aging Trends Study (7708 observations; participant-level split). In 200 separate, participant-unique drawings annotated for seven abnormalities, we evaluated Grad-CAM attribution alignment, matched-ink perturbation sensitivity, and linear probing of frozen representations. Sensitivity analyses covered region-of-interest definitions, data quality, and adjustment for CDT score. Results: On 1181 test observations, the quadratic weighted kappa was 0.740 and accuracy 0.678. Unadjusted analyses suggested abnormality-specific effects, including reduced hand-region attribution for missing or incorrect hands (q < 0.001) and significant perturbation sensitivity for three abnormalities. However, perturbation effects were as large in drawings without the abnormality. Within score levels, neither attribution nor perturbation sensitivity distinguished drawings with and without abnormalities. Within-score linear decodability remained for five abnormalities (AUROC 0.64–0.93), but not for uneven number spacing or same-length hands. Inter-rater agreement varied (κ 0.27–0.85). Conclusions: In this model and dataset, attribution and perturbation sensitivity mainly reflected overall drawing quality and the presence of intact hands and numerals. Abnormality-specific information was detectable only in the learned representation. Feature-level explainability evaluations should control for the prediction target, and saliency maps alone do not show that a model has learned interpretable abnormalities.

]]> TriHG-XAI: A Human-Grounded Framework for Triangulated Explainability Evaluation in Ordinal Clock Drawing Test Quality Prediction Ayat Elmyerigiy Emad Sami Jaha Alaa Bafail doi: 10.3390/diagnostics16223735 Diagnostics 2026-11-11 Diagnostics 2026-11-11 16 22 Article 3735 10.3390/diagnostics16223735 https://www.mdpi.com/2075-4418/16/22/3735 Diagnostics, Vol. 16, Pages 3734: Intestinal Behçet’s Disease Presenting as Recurrent Gastrointestinal Perforation: A Diagnostic Pitfall Mimicking Crohn’s Disease https://www.mdpi.com/2075-4418/16/22/3734 A 24-year-old man underwent four emergency surgeries for gastrointestinal perforation over a six-year period. Surgical pathology repeatedly suggested transmural inflammation with fissuring ulcers, favoring Crohn’s disease. However, the acute onset of each episode and the lack of typical Crohn’s disease-related chronic inflammatory symptoms between episodes were incompatible with the chronic course of Crohn’s disease. The histopathological finding of a tunnel-like ulcer, together with recurrent oral ulcers and acneiform folliculitis, led to a diagnosis of intestinal Behçet’s disease after multidisciplinary review. This case illustrates that when pathological morphology and clinical rhythm conflict, a comprehensive evaluation integrating the clinical history, extraintestinal manifestations, and histopathological findings is essential. 2026-11-11 Diagnostics, Vol. 16, Pages 3734: Intestinal Behçet’s Disease Presenting as Recurrent Gastrointestinal Perforation: A Diagnostic Pitfall Mimicking Crohn’s Disease

Diagnostics doi: 10.3390/diagnostics16223734

Authors: Libumu Axi Yufang Wang

A 24-year-old man underwent four emergency surgeries for gastrointestinal perforation over a six-year period. Surgical pathology repeatedly suggested transmural inflammation with fissuring ulcers, favoring Crohn’s disease. However, the acute onset of each episode and the lack of typical Crohn’s disease-related chronic inflammatory symptoms between episodes were incompatible with the chronic course of Crohn’s disease. The histopathological finding of a tunnel-like ulcer, together with recurrent oral ulcers and acneiform folliculitis, led to a diagnosis of intestinal Behçet’s disease after multidisciplinary review. This case illustrates that when pathological morphology and clinical rhythm conflict, a comprehensive evaluation integrating the clinical history, extraintestinal manifestations, and histopathological findings is essential.

]]> Intestinal Behçet’s Disease Presenting as Recurrent Gastrointestinal Perforation: A Diagnostic Pitfall Mimicking Crohn’s Disease Libumu Axi Yufang Wang doi: 10.3390/diagnostics16223734 Diagnostics 2026-11-11 Diagnostics 2026-11-11 16 22 Interesting Images 3734 10.3390/diagnostics16223734 https://www.mdpi.com/2075-4418/16/22/3734 Diagnostics, Vol. 16, Pages 3732: Computed Tomography-Derived Myosteatosis and Diaphragmatic Crus Morphology Are Associated with Radiologically Documented Recurrence Following Sliding Hiatal Hernia Repair: A Retrospective Cohort Study https://www.mdpi.com/2075-4418/16/22/3732 Background: Systemic muscle composition and local diaphragmatic crus morphology may be associated with recurrence after sliding hiatal hernia repair. This study evaluated the associations of preoperative CT-derived muscle measurements with radiologically documented recurrence after primary type I sliding hiatal hernia repair. Methods: This retrospective single-center study identified 132 patients who underwent repair between January 2015 and July 2024. The primary recurrence analysis was restricted to 48 patients with postoperative CT. Preoperative measurements included L3 skeletal muscle attenuation and diaphragmatic crus thickness and attenuation. Associations were evaluated using between-group comparisons and separate univariable Firth penalized logistic regression models. Multivariable models and analyses involving the overall cohort were retained as exploratory supplementary analyses. Results: Among the 48 CT-imaged patients, 15 had radiologically documented recurrence and 33 had no recurrence detected on available CT. Myosteatosis was more frequent in patients with recurrence (80.0% versus 18.2%; p < 0.001). Mean crus attenuation (31.53 ± 4.69 versus 37.21 ± 3.61 HU) and thickness (5.51 ± 0.61 versus 6.39 ± 0.71 mm) were lower in patients with recurrence (both p < 0.001). In separate univariable models, myosteatosis (OR, 15.11; 95% CI, 3.84–75.00), lower crus attenuation (OR per 1-HU decrease, 1.37; 95% CI, 1.15–1.72), and reduced crus thickness (OR per 1-mm decrease, 8.02; 95% CI, 2.42–44.33) were associated with documented recurrence. These estimates were unadjusted and imprecise. Conclusions: Among selectively CT-imaged patients, myosteatosis and adverse crural muscle measurements were associated with documented recurrence. Limited events, nonstandardized imaging, and uncontrolled confounding preclude definitive prognostic conclusions. Larger studies with standardized postoperative imaging are required. 2026-11-11 Diagnostics, Vol. 16, Pages 3732: Computed Tomography-Derived Myosteatosis and Diaphragmatic Crus Morphology Are Associated with Radiologically Documented Recurrence Following Sliding Hiatal Hernia Repair: A Retrospective Cohort Study

Diagnostics doi: 10.3390/diagnostics16223732

Authors: Mahmut Baran Yerlikaya Serhat Binici Adem Aslan Harun Bayram Fırat Aslan Ali Rıza Karayıl Ozan Okyay Abdülselam Özdemir İlyas Dündar Orhan Beger Burhan Beger

Background: Systemic muscle composition and local diaphragmatic crus morphology may be associated with recurrence after sliding hiatal hernia repair. This study evaluated the associations of preoperative CT-derived muscle measurements with radiologically documented recurrence after primary type I sliding hiatal hernia repair. Methods: This retrospective single-center study identified 132 patients who underwent repair between January 2015 and July 2024. The primary recurrence analysis was restricted to 48 patients with postoperative CT. Preoperative measurements included L3 skeletal muscle attenuation and diaphragmatic crus thickness and attenuation. Associations were evaluated using between-group comparisons and separate univariable Firth penalized logistic regression models. Multivariable models and analyses involving the overall cohort were retained as exploratory supplementary analyses. Results: Among the 48 CT-imaged patients, 15 had radiologically documented recurrence and 33 had no recurrence detected on available CT. Myosteatosis was more frequent in patients with recurrence (80.0% versus 18.2%; p < 0.001). Mean crus attenuation (31.53 ± 4.69 versus 37.21 ± 3.61 HU) and thickness (5.51 ± 0.61 versus 6.39 ± 0.71 mm) were lower in patients with recurrence (both p < 0.001). In separate univariable models, myosteatosis (OR, 15.11; 95% CI, 3.84–75.00), lower crus attenuation (OR per 1-HU decrease, 1.37; 95% CI, 1.15–1.72), and reduced crus thickness (OR per 1-mm decrease, 8.02; 95% CI, 2.42–44.33) were associated with documented recurrence. These estimates were unadjusted and imprecise. Conclusions: Among selectively CT-imaged patients, myosteatosis and adverse crural muscle measurements were associated with documented recurrence. Limited events, nonstandardized imaging, and uncontrolled confounding preclude definitive prognostic conclusions. Larger studies with standardized postoperative imaging are required.

]]> Computed Tomography-Derived Myosteatosis and Diaphragmatic Crus Morphology Are Associated with Radiologically Documented Recurrence Following Sliding Hiatal Hernia Repair: A Retrospective Cohort Study Mahmut Baran Yerlikaya Serhat Binici Adem Aslan Harun Bayram Fırat Aslan Ali Rıza Karayıl Ozan Okyay Abdülselam Özdemir İlyas Dündar Orhan Beger Burhan Beger doi: 10.3390/diagnostics16223732 Diagnostics 2026-11-11 Diagnostics 2026-11-11 16 22 Article 3732 10.3390/diagnostics16223732 https://www.mdpi.com/2075-4418/16/22/3732 Diagnostics, Vol. 16, Pages 3733: Multi-Parametric Spectral Detector CT for the Assessment of Focal Liver Lesions: Evaluation of Readers’ Diagnostic Confidence and Economic Effects https://www.mdpi.com/2075-4418/16/22/3733 Background/Objectives: Characterization of small liver lesions on computed tomography (CT) remains challenging. This study evaluated whether spectral detector CT (SDCT) improves subjective diagnostic confidence in the characterization of focal hypoperfused liver lesions using additional spectral information and assessed its potential economic impact. Methods: In this IRB-approved retrospective study, 100 patients with 229 focal hypoperfused liver lesions who underwent SDCT were included. Images were evaluated in three consecutive reading sessions using (1) conventional polychromatic images (conv), (2) conventional plus monoenergetic images at 40, 50, and 60 keV (monoE), and (3) a multiparametric SDCT approach (mSDCT) combining conventional and spectral reconstructions, including iodine density (ID) and effective atomic number (Zeff) images. Lesions were characterized, and subjective diagnostic confidence was rated on a 5-point scale. Diagnostic performance was compared, and potential economic savings were estimated. Results: mSDCT yielded the highest diagnostic confidence in 130 lesions, compared with 36 lesions for conventional CT. Diagnostic confidence increased significantly from conventional CT through monoE to mSDCT (median scores: 3, 4, 4, 4, and 5 for conventional CT, 40-, 50-, and 60-keV monoE, and mSDCT, respectively; all p < 0.001). For lesions ≤ 10 mm, sensitivity was comparable between conventional CT and mSDCT, whereas mSDCT significantly improved specificity (85.0% vs. 97.9%) and diagnostic accuracy (86.4% vs. 96.7%; p < 0.001). Conclusions: Multiparametric SDCT significantly improves radiologists’ diagnostic confidence in characterizing focal hypoperfused liver lesions, particularly lesions ≤ 10 mm in oncologic patients. Increased diagnostic confidence may reduce the need for additional imaging or biopsy, potentially enabling faster and less costly diagnostic workups. 2026-11-11 Diagnostics, Vol. 16, Pages 3733: Multi-Parametric Spectral Detector CT for the Assessment of Focal Liver Lesions: Evaluation of Readers’ Diagnostic Confidence and Economic Effects

Diagnostics doi: 10.3390/diagnostics16223733

Authors: Mathilda Weisthoff Marvin A. Spurek Karin Rau Robert Rau Stefan Haneder Christoph Bartz Christian Nelles Robert Wawer Matos Reimer Nils Große Hokamp David Maintz Simon Lennartz Thorsten Persigehl

Background/Objectives: Characterization of small liver lesions on computed tomography (CT) remains challenging. This study evaluated whether spectral detector CT (SDCT) improves subjective diagnostic confidence in the characterization of focal hypoperfused liver lesions using additional spectral information and assessed its potential economic impact. Methods: In this IRB-approved retrospective study, 100 patients with 229 focal hypoperfused liver lesions who underwent SDCT were included. Images were evaluated in three consecutive reading sessions using (1) conventional polychromatic images (conv), (2) conventional plus monoenergetic images at 40, 50, and 60 keV (monoE), and (3) a multiparametric SDCT approach (mSDCT) combining conventional and spectral reconstructions, including iodine density (ID) and effective atomic number (Zeff) images. Lesions were characterized, and subjective diagnostic confidence was rated on a 5-point scale. Diagnostic performance was compared, and potential economic savings were estimated. Results: mSDCT yielded the highest diagnostic confidence in 130 lesions, compared with 36 lesions for conventional CT. Diagnostic confidence increased significantly from conventional CT through monoE to mSDCT (median scores: 3, 4, 4, 4, and 5 for conventional CT, 40-, 50-, and 60-keV monoE, and mSDCT, respectively; all p < 0.001). For lesions ≤ 10 mm, sensitivity was comparable between conventional CT and mSDCT, whereas mSDCT significantly improved specificity (85.0% vs. 97.9%) and diagnostic accuracy (86.4% vs. 96.7%; p < 0.001). Conclusions: Multiparametric SDCT significantly improves radiologists’ diagnostic confidence in characterizing focal hypoperfused liver lesions, particularly lesions ≤ 10 mm in oncologic patients. Increased diagnostic confidence may reduce the need for additional imaging or biopsy, potentially enabling faster and less costly diagnostic workups.

]]> Multi-Parametric Spectral Detector CT for the Assessment of Focal Liver Lesions: Evaluation of Readers’ Diagnostic Confidence and Economic Effects Mathilda Weisthoff Marvin A. Spurek Karin Rau Robert Rau Stefan Haneder Christoph Bartz Christian Nelles Robert Wawer Matos Reimer Nils Große Hokamp David Maintz Simon Lennartz Thorsten Persigehl doi: 10.3390/diagnostics16223733 Diagnostics 2026-11-11 Diagnostics 2026-11-11 16 22 Article 3733 10.3390/diagnostics16223733 https://www.mdpi.com/2075-4418/16/22/3733 Diagnostics, Vol. 16, Pages 3731: Exploratory Evaluation of TBR Thresholds for Arterial [18F]F-FAPI-74 PET/CT https://www.mdpi.com/2075-4418/16/22/3731 Background/Objectives: Fibroblast activation protein inhibitor (FAPI)-directed PET/CT has emerged as a promising approach for non-invasive assessment of arterial wall pathology. While a target-to-background ratio (TBR) threshold of 1.6 has previously been applied for vascular [68Ga]Ga-FAPI-04 imaging, no established threshold exists for [18F]F-FAPI-74. Given differences in physical imaging characteristics and tracer kinetics, this study systematically evaluated candidate TBR thresholds for arterial [18F]F-FAPI-74 uptake, using CT-derived calcification as a morphological comparator. Methods: Seventy-two oncological patients undergoing [18F]F-FAPI-74 PET/CT were retrospectively analyzed. Six vascular territories were assessed for focal vessel wall-associated tracer uptake and CT-derived calcification. Three primary candidate TBR thresholds (1.2, 1.4, and 1.6) were selected for focused comparison, while complementary thresholds from 1.0 to 2.0 in increments of 0.1 were assessed descriptively. For each threshold, the number of FAPI-positive sites, proportion of FAPI-positive sites with concomitant calcification, and proportion of calcification-positive sites with concomitant FAPI uptake were determined. All co-localization measures were interpreted as descriptive morphological comparisons and not as measures of biological FAP expression, diagnostic sensitivity, or diagnostic accuracy. Results: Focal arterial uptake was detected in 69/72 patients (95.8%) at a TBR threshold of 1.2, 61/72 (84.7%) at 1.4 and 38/72 (52.8%) at 1.6. The corresponding numbers of FAPI-positive sites were 896, 452 and 220. Among the three primary candidate thresholds, the proportion of FAPI-positive sites with concomitant calcification remained broadly comparable (66.7%, 60.2%, and 68.2%, respectively), whereas the proportion of calcification-positive sites with concomitant FAPI uptake decreased from 23.4% at a TBR threshold of 1.2 to 10.7% at 1.4 and 5.9% at 1.6. Across the broader TBR range, lower thresholds, including 1.0 and 1.1, yielded greater site detection and numerically higher calcification co-localization than the TBR threshold of 1.2, and no unique empirical optimum was identified. Conclusions: A TBR threshold of 1.2 represents a pragmatic candidate threshold within the predefined primary range rather than an empirically optimized cut-off. Prospective validation in dedicated cardiovascular cohorts using standardized imaging protocols and biological reference standards is required before a generally applicable threshold for arterial [18F]F-FAPI-74 imaging can be established. 2026-11-11 Diagnostics, Vol. 16, Pages 3731: Exploratory Evaluation of TBR Thresholds for Arterial [18F]F-FAPI-74 PET/CT

Diagnostics doi: 10.3390/diagnostics16223731

Authors: Charlotte Kreuer Maximilian G. Fischer Franz Josef Gildehaus Matthias Brendel Sarah M. Berthold Adrien Holzgreve Konstantin Stark Takahiro Higuchi Frederik L. Giesel Rudolf A. Werner Sophie C. Siegmund

Background/Objectives: Fibroblast activation protein inhibitor (FAPI)-directed PET/CT has emerged as a promising approach for non-invasive assessment of arterial wall pathology. While a target-to-background ratio (TBR) threshold of 1.6 has previously been applied for vascular [68Ga]Ga-FAPI-04 imaging, no established threshold exists for [18F]F-FAPI-74. Given differences in physical imaging characteristics and tracer kinetics, this study systematically evaluated candidate TBR thresholds for arterial [18F]F-FAPI-74 uptake, using CT-derived calcification as a morphological comparator. Methods: Seventy-two oncological patients undergoing [18F]F-FAPI-74 PET/CT were retrospectively analyzed. Six vascular territories were assessed for focal vessel wall-associated tracer uptake and CT-derived calcification. Three primary candidate TBR thresholds (1.2, 1.4, and 1.6) were selected for focused comparison, while complementary thresholds from 1.0 to 2.0 in increments of 0.1 were assessed descriptively. For each threshold, the number of FAPI-positive sites, proportion of FAPI-positive sites with concomitant calcification, and proportion of calcification-positive sites with concomitant FAPI uptake were determined. All co-localization measures were interpreted as descriptive morphological comparisons and not as measures of biological FAP expression, diagnostic sensitivity, or diagnostic accuracy. Results: Focal arterial uptake was detected in 69/72 patients (95.8%) at a TBR threshold of 1.2, 61/72 (84.7%) at 1.4 and 38/72 (52.8%) at 1.6. The corresponding numbers of FAPI-positive sites were 896, 452 and 220. Among the three primary candidate thresholds, the proportion of FAPI-positive sites with concomitant calcification remained broadly comparable (66.7%, 60.2%, and 68.2%, respectively), whereas the proportion of calcification-positive sites with concomitant FAPI uptake decreased from 23.4% at a TBR threshold of 1.2 to 10.7% at 1.4 and 5.9% at 1.6. Across the broader TBR range, lower thresholds, including 1.0 and 1.1, yielded greater site detection and numerically higher calcification co-localization than the TBR threshold of 1.2, and no unique empirical optimum was identified. Conclusions: A TBR threshold of 1.2 represents a pragmatic candidate threshold within the predefined primary range rather than an empirically optimized cut-off. Prospective validation in dedicated cardiovascular cohorts using standardized imaging protocols and biological reference standards is required before a generally applicable threshold for arterial [18F]F-FAPI-74 imaging can be established.

]]> Exploratory Evaluation of TBR Thresholds for Arterial [18F]F-FAPI-74 PET/CT Charlotte Kreuer Maximilian G. Fischer Franz Josef Gildehaus Matthias Brendel Sarah M. Berthold Adrien Holzgreve Konstantin Stark Takahiro Higuchi Frederik L. Giesel Rudolf A. Werner Sophie C. Siegmund doi: 10.3390/diagnostics16223731 Diagnostics 2026-11-11 Diagnostics 2026-11-11 16 22 Article 3731 10.3390/diagnostics16223731 https://www.mdpi.com/2075-4418/16/22/3731 Diagnostics, Vol. 16, Pages 3730: Lifestyle and Clinical Correlates of Myosteatosis Among African Caribbean Men and Women https://www.mdpi.com/2075-4418/16/22/3730 Background/Objectives: Myosteatosis, i.e., adiposity in and around skeletal muscle, is a hallmark of adverse muscle aging, more common among women than men, and associated with several major health outcomes, including cardiometabolic diseases and functional decline. We investigated lifestyle and clinical correlates of skeletal muscle adiposity among an understudied cohort of Afro-Caribbean men and women. Methods: Among 213 men and 530 women aged 50–80 from the Tobago Health Study, several lifestyle and clinical factors were assessed, including accelerometry-derived physical activity and sleep duration, diet, and medications. Lifestyle risk scores were based on smoking, alcohol, physical activity, and body mass index. Calf muscle density was measured using peripheral quantitative computed tomography, with lower values suggesting more muscle adiposity. Results: Women were more likely to abstain from cigarettes and alcohol, but less physically active, with more sugar intake and lower muscle density than men. Using Isotemporal Substitution, cross-sectionally replacing sedentary time with sleep or light-intensity physical activity was significantly associated with higher muscle density. In multivariable models, older age, larger waist circumference, and taking diabetes medications were cross-sectionally associated with lower muscle density, as well as shorter sleep among men and taking anti-hypertensive medications among women. Conclusions: Older Afro-Caribbean women vs. men had healthier substance habits, but lower activity and muscle density, suggesting more muscle adiposity. Modifiable behaviors, particularly sedentary time, sleep duration, and light-intensity physical activity were strongly associated with muscle density. Interventions that replace sedentary time with light-intensity physical activity and sleep may be feasible and sustainable approaches to reduce myosteatosis. 2026-11-11 Diagnostics, Vol. 16, Pages 3730: Lifestyle and Clinical Correlates of Myosteatosis Among African Caribbean Men and Women

Diagnostics doi: 10.3390/diagnostics16223730

Authors: Megan M. Marron Ryan K. Cvejkus Adrianna I. Acevedo-Fontanez Joseph M. Zmuda Victor Wheeler Iva Miljkovic

Background/Objectives: Myosteatosis, i.e., adiposity in and around skeletal muscle, is a hallmark of adverse muscle aging, more common among women than men, and associated with several major health outcomes, including cardiometabolic diseases and functional decline. We investigated lifestyle and clinical correlates of skeletal muscle adiposity among an understudied cohort of Afro-Caribbean men and women. Methods: Among 213 men and 530 women aged 50–80 from the Tobago Health Study, several lifestyle and clinical factors were assessed, including accelerometry-derived physical activity and sleep duration, diet, and medications. Lifestyle risk scores were based on smoking, alcohol, physical activity, and body mass index. Calf muscle density was measured using peripheral quantitative computed tomography, with lower values suggesting more muscle adiposity. Results: Women were more likely to abstain from cigarettes and alcohol, but less physically active, with more sugar intake and lower muscle density than men. Using Isotemporal Substitution, cross-sectionally replacing sedentary time with sleep or light-intensity physical activity was significantly associated with higher muscle density. In multivariable models, older age, larger waist circumference, and taking diabetes medications were cross-sectionally associated with lower muscle density, as well as shorter sleep among men and taking anti-hypertensive medications among women. Conclusions: Older Afro-Caribbean women vs. men had healthier substance habits, but lower activity and muscle density, suggesting more muscle adiposity. Modifiable behaviors, particularly sedentary time, sleep duration, and light-intensity physical activity were strongly associated with muscle density. Interventions that replace sedentary time with light-intensity physical activity and sleep may be feasible and sustainable approaches to reduce myosteatosis.

]]> Lifestyle and Clinical Correlates of Myosteatosis Among African Caribbean Men and Women Megan M. Marron Ryan K. Cvejkus Adrianna I. Acevedo-Fontanez Joseph M. Zmuda Victor Wheeler Iva Miljkovic doi: 10.3390/diagnostics16223730 Diagnostics 2026-11-11 Diagnostics 2026-11-11 16 22 Article 3730 10.3390/diagnostics16223730 https://www.mdpi.com/2075-4418/16/22/3730 Diagnostics, Vol. 16, Pages 3727: HPV16/18 Genotype and Histologic High-Grade Disease in Women with ASC-H Cytology: A Systematic Review of Genotype-Stratified Outcomes https://www.mdpi.com/2075-4418/16/22/3727 Background/Objectives: Human papillomavirus (HPV) genotyping may stratify histologic risk among women with atypical squamous cells that cannot exclude high-grade squamous intraepithelial lesion (ASC-H). We evaluated genotype-specific high-grade outcomes. Methods: PubMed and Europe PMC were searched on 1 October 2026 and updated on 7 October 2026. Two reviewers independently screened, extracted, and appraised studies in accordance with PRISMA 2020. Eligible English language studies provided ASC-H-specific histologic outcomes for HPV16/18-defined and comparator groups. Risk of bias was appraised with an adapted QUADAS-2 framework (the protocol-specified Joanna Briggs Institute prevalence checklist is reported in an appendix), and certainty was rated with GRADE. An exploratory restricted meta-analysis compared HPV16/18 with other high-risk HPV (hrHPV) for CIN2+/HSIL+ using random effects and modified Hartung–Knapp confidence intervals. Results: Sixteen studies in 17 reports were included; six contributed 1655 women to the restricted comparison. The pooled risk ratio was 1.19 (95% confidence interval, 0.94–1.49), with substantial heterogeneity (I2 = 64.9%) and a prediction interval of 0.70–2.01. The results varied with study selection and genotype definition. In four studies with at least 30 hrHPV-negative women, high-grade outcomes occurred in 6.8–18.4%, and HPV-negative carcinomas were reported. Leave-one-out, screening context, and verification-restricted analyses did not show a consistent difference (histology in all participants: RR 1.01, 0.63–1.62). Incomplete verification, confounding by age and screening context, heterogeneous assays and populations, and inaccessible reports limited confidence; certainty was very low for both outcomes. Conclusions: A modest relative difference between HPV16/18 and other hrHPV types cannot be excluded, but the pooled evidence does not demonstrate a consistent incremental risk difference. Other hrHPV types and negative hrHPV results do not exclude high-grade disease. These findings are consistent with current guidance for colposcopic evaluation of all ASC-H without genotype-based deferral. 2026-11-11 Diagnostics, Vol. 16, Pages 3727: HPV16/18 Genotype and Histologic High-Grade Disease in Women with ASC-H Cytology: A Systematic Review of Genotype-Stratified Outcomes

Diagnostics doi: 10.3390/diagnostics16223727

Authors: (Mazilu) Rusu Chiriac Faur Heredea Chiriac

Background/Objectives: Human papillomavirus (HPV) genotyping may stratify histologic risk among women with atypical squamous cells that cannot exclude high-grade squamous intraepithelial lesion (ASC-H). We evaluated genotype-specific high-grade outcomes. Methods: PubMed and Europe PMC were searched on 1 October 2026 and updated on 7 October 2026. Two reviewers independently screened, extracted, and appraised studies in accordance with PRISMA 2020. Eligible English language studies provided ASC-H-specific histologic outcomes for HPV16/18-defined and comparator groups. Risk of bias was appraised with an adapted QUADAS-2 framework (the protocol-specified Joanna Briggs Institute prevalence checklist is reported in an appendix), and certainty was rated with GRADE. An exploratory restricted meta-analysis compared HPV16/18 with other high-risk HPV (hrHPV) for CIN2+/HSIL+ using random effects and modified Hartung–Knapp confidence intervals. Results: Sixteen studies in 17 reports were included; six contributed 1655 women to the restricted comparison. The pooled risk ratio was 1.19 (95% confidence interval, 0.94–1.49), with substantial heterogeneity (I2 = 64.9%) and a prediction interval of 0.70–2.01. The results varied with study selection and genotype definition. In four studies with at least 30 hrHPV-negative women, high-grade outcomes occurred in 6.8–18.4%, and HPV-negative carcinomas were reported. Leave-one-out, screening context, and verification-restricted analyses did not show a consistent difference (histology in all participants: RR 1.01, 0.63–1.62). Incomplete verification, confounding by age and screening context, heterogeneous assays and populations, and inaccessible reports limited confidence; certainty was very low for both outcomes. Conclusions: A modest relative difference between HPV16/18 and other hrHPV types cannot be excluded, but the pooled evidence does not demonstrate a consistent incremental risk difference. Other hrHPV types and negative hrHPV results do not exclude high-grade disease. These findings are consistent with current guidance for colposcopic evaluation of all ASC-H without genotype-based deferral.

]]> HPV16/18 Genotype and Histologic High-Grade Disease in Women with ASC-H Cytology: A Systematic Review of Genotype-Stratified Outcomes (Mazilu) Rusu Chiriac Faur Heredea Chiriac doi: 10.3390/diagnostics16223727 Diagnostics 2026-11-11 Diagnostics 2026-11-11 16 22 Systematic Review 3727 10.3390/diagnostics16223727 https://www.mdpi.com/2075-4418/16/22/3727 Diagnostics, Vol. 16, Pages 3728: Comparison of Cone-Beam CT, Photon-Counting Detector CT and Micro-CT for Imaging Bone Graft Biomaterials and Three-Dimensional Printed Calcium Phosphate Scaffolds: An Ex Vivo Study https://www.mdpi.com/2075-4418/16/22/3728 Background/Objectives: Cone-beam computed tomography (CBCT) is widely used in dentomaxillofacial imaging for evaluating bone grafts and implant-related procedures; however, image quality is often compromised by metal-induced artefacts. This study compared CBCT, photon-counting detector CT (PCD-CT), and micro-computed tomography (µCT) for imaging clinically relevant bone graft materials and three-dimensional printed calcium phosphate scaffolds, focusing on biomaterial visualisation and titanium artefact reduction. Methods: Four bovine mandibles were prepared with standardized cylindrical defects containing eight bone substitute materials and 3D-printed calcium phosphate scaffolds, with or without surrounding titanium cages. Specimens were imaged using CBCT and PCD-CT with low-dose and maximum-dose ultra-high-resolution acquisition protocols, and µCT. Two readers independently assessed image interpretability, biomaterial visualisation, and metal artefact severity using a five-point scoring system. Inter-reader agreement was evaluated using weighted Cohen’s kappa. Results: µCT provided the highest spatial resolution and served as the ex vivo reference standard. Under the acquisition and reconstruction protocols evaluated, PCD-CT provided favorable visualization of scaffold architecture and reduced the visual impact of titanium-induced artefacts compared with CBCT. High-energy virtual monoenergetic reconstructions (≥130 keV) further reduced beam-hardening and streak artefacts, although the optimal reconstruction energy may depend on the biomaterial and diagnostic task. Without titanium cages, PCD-CT and µCT achieved higher image interpretability scores than CBCT. With titanium cages, CBCT frequently became non-diagnostic, whereas PCD-CT maintained good visualisation of most biomaterials. Inter-reader agreement ranged from substantial to almost perfect. Conclusions: In this exploratory ex vivo study, the evaluated PCD-CT protocols provided favorable qualitative visualization of several bone graft materials and three-dimensional printed calcium phosphate scaffolds compared with the evaluated CBCT protocol, particularly in the presence of titanium cages. However, the protocols were not dose-matched, and differences in acquisition and reconstruction parameters prevent attributing the observed findings exclusively to detector technology. The study does not establish PCD-CT superiority at equivalent radiation doses or demonstrate clinical performance in longitudinal bone-regeneration monitoring. Further dose-matched studies incorporating objective image-quality measurements and clinical validation are required. 2026-11-11 Diagnostics, Vol. 16, Pages 3728: Comparison of Cone-Beam CT, Photon-Counting Detector CT and Micro-CT for Imaging Bone Graft Biomaterials and Three-Dimensional Printed Calcium Phosphate Scaffolds: An Ex Vivo Study

Diagnostics doi: 10.3390/diagnostics16223728

Authors: Julien Guerrero Paula Korn Adib Al-Haj Husain Victor Mergen Tristan T. Demmert Hatem Alkadhi Ana Pérez Domínguez Richard F. Richter Thomas Flohr Maximilian Eberhard Hermann Wagner Harald Essig Franz E. Weber Bernd Stadlinger

Background/Objectives: Cone-beam computed tomography (CBCT) is widely used in dentomaxillofacial imaging for evaluating bone grafts and implant-related procedures; however, image quality is often compromised by metal-induced artefacts. This study compared CBCT, photon-counting detector CT (PCD-CT), and micro-computed tomography (µCT) for imaging clinically relevant bone graft materials and three-dimensional printed calcium phosphate scaffolds, focusing on biomaterial visualisation and titanium artefact reduction. Methods: Four bovine mandibles were prepared with standardized cylindrical defects containing eight bone substitute materials and 3D-printed calcium phosphate scaffolds, with or without surrounding titanium cages. Specimens were imaged using CBCT and PCD-CT with low-dose and maximum-dose ultra-high-resolution acquisition protocols, and µCT. Two readers independently assessed image interpretability, biomaterial visualisation, and metal artefact severity using a five-point scoring system. Inter-reader agreement was evaluated using weighted Cohen’s kappa. Results: µCT provided the highest spatial resolution and served as the ex vivo reference standard. Under the acquisition and reconstruction protocols evaluated, PCD-CT provided favorable visualization of scaffold architecture and reduced the visual impact of titanium-induced artefacts compared with CBCT. High-energy virtual monoenergetic reconstructions (≥130 keV) further reduced beam-hardening and streak artefacts, although the optimal reconstruction energy may depend on the biomaterial and diagnostic task. Without titanium cages, PCD-CT and µCT achieved higher image interpretability scores than CBCT. With titanium cages, CBCT frequently became non-diagnostic, whereas PCD-CT maintained good visualisation of most biomaterials. Inter-reader agreement ranged from substantial to almost perfect. Conclusions: In this exploratory ex vivo study, the evaluated PCD-CT protocols provided favorable qualitative visualization of several bone graft materials and three-dimensional printed calcium phosphate scaffolds compared with the evaluated CBCT protocol, particularly in the presence of titanium cages. However, the protocols were not dose-matched, and differences in acquisition and reconstruction parameters prevent attributing the observed findings exclusively to detector technology. The study does not establish PCD-CT superiority at equivalent radiation doses or demonstrate clinical performance in longitudinal bone-regeneration monitoring. Further dose-matched studies incorporating objective image-quality measurements and clinical validation are required.

]]> Comparison of Cone-Beam CT, Photon-Counting Detector CT and Micro-CT for Imaging Bone Graft Biomaterials and Three-Dimensional Printed Calcium Phosphate Scaffolds: An Ex Vivo Study Julien Guerrero Paula Korn Adib Al-Haj Husain Victor Mergen Tristan T. Demmert Hatem Alkadhi Ana Pérez Domínguez Richard F. Richter Thomas Flohr Maximilian Eberhard Hermann Wagner Harald Essig Franz E. Weber Bernd Stadlinger doi: 10.3390/diagnostics16223728 Diagnostics 2026-11-11 Diagnostics 2026-11-11 16 22 Article 3728 10.3390/diagnostics16223728 https://www.mdpi.com/2075-4418/16/22/3728 Diagnostics, Vol. 16, Pages 3729: Unprotected TAVI with Critically Low LMCA Height: The Importance of Individualized Anatomical Assessment https://www.mdpi.com/2075-4418/16/22/3729 A 66-year-old woman with severe symptomatic aortic stenosis (STS-PROM 5.15%; EuroSCORE II 3.66%), right carotid occlusion, 50% left carotid stenosis, and a preference for TAVI underwent multidisciplinary assessment. Computed tomography demonstrated a 6 mm left main coronary artery (LMCA) ostial height, hypoplastic right coronary artery, 31 mm left coronary sinus, and no bulky calcification facing the LMCA. Following Heart Team assessment of obstruction risk and the potential complications of prophylactic stenting, transfemoral TAVI was performed without coronary protection using a 29 mm recapturable self-expanding valve, with emergency revascularization, hemodynamic support, and surgical backup available. Preserved left coronary perfusion after 18 mm balloon predilatation provided reassurance but could not exclude obstruction during valve deployment. Recovery was uneventful, with no reported adverse cardiovascular events during approximately 18 months of follow-up. Favorable sinus anatomy may inform procedural planning but cannot independently establish protection against coronary obstruction. This single case illustrates individualized anatomical assessment and Heart Team decision-making, not the general safety of omitting coronary protection in similarly high-risk patients. 2026-11-11 Diagnostics, Vol. 16, Pages 3729: Unprotected TAVI with Critically Low LMCA Height: The Importance of Individualized Anatomical Assessment

Diagnostics doi: 10.3390/diagnostics16223729

Authors: Alper Karakus Mustafa Aytek Simsek Selcuk Gormez Omer Faruk Suluker Melek Ducem Akgul Akin Emir Dokuyucu Duygu Tuncar Can Yucel Karabay

A 66-year-old woman with severe symptomatic aortic stenosis (STS-PROM 5.15%; EuroSCORE II 3.66%), right carotid occlusion, 50% left carotid stenosis, and a preference for TAVI underwent multidisciplinary assessment. Computed tomography demonstrated a 6 mm left main coronary artery (LMCA) ostial height, hypoplastic right coronary artery, 31 mm left coronary sinus, and no bulky calcification facing the LMCA. Following Heart Team assessment of obstruction risk and the potential complications of prophylactic stenting, transfemoral TAVI was performed without coronary protection using a 29 mm recapturable self-expanding valve, with emergency revascularization, hemodynamic support, and surgical backup available. Preserved left coronary perfusion after 18 mm balloon predilatation provided reassurance but could not exclude obstruction during valve deployment. Recovery was uneventful, with no reported adverse cardiovascular events during approximately 18 months of follow-up. Favorable sinus anatomy may inform procedural planning but cannot independently establish protection against coronary obstruction. This single case illustrates individualized anatomical assessment and Heart Team decision-making, not the general safety of omitting coronary protection in similarly high-risk patients.

]]> Unprotected TAVI with Critically Low LMCA Height: The Importance of Individualized Anatomical Assessment Alper Karakus Mustafa Aytek Simsek Selcuk Gormez Omer Faruk Suluker Melek Ducem Akgul Akin Emir Dokuyucu Duygu Tuncar Can Yucel Karabay doi: 10.3390/diagnostics16223729 Diagnostics 2026-11-11 Diagnostics 2026-11-11 16 22 Interesting Images 3729 10.3390/diagnostics16223729 https://www.mdpi.com/2075-4418/16/22/3729 Diagnostics, Vol. 16, Pages 3726: Longitudinal SPECT Assessment of Regional Cerebral Perfusion Associated with Nicergoline Use in Parkinson’s Disease Without Dementia: An Exploratory Observational Study https://www.mdpi.com/2075-4418/16/22/3726 Background/Objectives: Cerebral hypoperfusion has been reported in Parkinson’s disease (PD), including in patients without dementia. We explored whether long-term nicergoline use was associated with longitudinal changes in relative regional cerebral blood flow (rCBF) and clinical outcomes in non-demented PD. Methods: Thirty patients with idiopathic PD without dementia underwent Unified Parkinson’s Disease Rating Scale (UPDRS) assessment and 99mTc-ethyl cysteinate dimer brain perfusion SPECT at baseline and again after 2–4 years. Eighteen patients received nicergoline (30 mg twice daily) with standard dopaminergic treatment, whereas 12 received dopaminergic treatment without nicergoline. Treatment allocation was non-randomized. Longitudinal SPECT change images were analyzed in SPM12. The voxel-wise group comparison used p < 0.001 uncorrected with a cluster extent threshold of ≥50 voxels and was considered exploratory because no correction for multiple comparisons was applied. Results: Baseline clinical characteristics did not differ significantly between groups, although age was numerically higher in the nicergoline group (72.4 ± 6.44 vs. 66.8 ± 9.14 years; p = 0.057). Changes in UPDRS scores, Hoehn and Yahr stage, and levodopa equivalent daily dose did not differ significantly between groups. A single 76-voxel cluster showed a greater relative perfusion increase in the right temporal fusiform cortex (Brodmann area 37; peak MNI coordinate 34, −40, −22; t = 4.07; uncorrected p < 0.001) in the nicergoline group. Conclusions: Long-term nicergoline exposure was associated with an uncorrected group-level difference in right fusiform relative perfusion without corresponding clinical improvement. Because the finding was based on a small, non-randomized cohort and an uncorrected voxel-wise threshold, it should not be interpreted as evidence of therapeutic efficacy or a cholinergic/cognitive benefit. Larger randomized studies with multiplicity control and clinically relevant cognitive outcomes are required. 2026-11-11 Diagnostics, Vol. 16, Pages 3726: Longitudinal SPECT Assessment of Regional Cerebral Perfusion Associated with Nicergoline Use in Parkinson’s Disease Without Dementia: An Exploratory Observational Study

Diagnostics doi: 10.3390/diagnostics16223726

Authors: Byungseok Kim Seung-Hee Na In-Uk Song Yong-An Chung

Background/Objectives: Cerebral hypoperfusion has been reported in Parkinson’s disease (PD), including in patients without dementia. We explored whether long-term nicergoline use was associated with longitudinal changes in relative regional cerebral blood flow (rCBF) and clinical outcomes in non-demented PD. Methods: Thirty patients with idiopathic PD without dementia underwent Unified Parkinson’s Disease Rating Scale (UPDRS) assessment and 99mTc-ethyl cysteinate dimer brain perfusion SPECT at baseline and again after 2–4 years. Eighteen patients received nicergoline (30 mg twice daily) with standard dopaminergic treatment, whereas 12 received dopaminergic treatment without nicergoline. Treatment allocation was non-randomized. Longitudinal SPECT change images were analyzed in SPM12. The voxel-wise group comparison used p < 0.001 uncorrected with a cluster extent threshold of ≥50 voxels and was considered exploratory because no correction for multiple comparisons was applied. Results: Baseline clinical characteristics did not differ significantly between groups, although age was numerically higher in the nicergoline group (72.4 ± 6.44 vs. 66.8 ± 9.14 years; p = 0.057). Changes in UPDRS scores, Hoehn and Yahr stage, and levodopa equivalent daily dose did not differ significantly between groups. A single 76-voxel cluster showed a greater relative perfusion increase in the right temporal fusiform cortex (Brodmann area 37; peak MNI coordinate 34, −40, −22; t = 4.07; uncorrected p < 0.001) in the nicergoline group. Conclusions: Long-term nicergoline exposure was associated with an uncorrected group-level difference in right fusiform relative perfusion without corresponding clinical improvement. Because the finding was based on a small, non-randomized cohort and an uncorrected voxel-wise threshold, it should not be interpreted as evidence of therapeutic efficacy or a cholinergic/cognitive benefit. Larger randomized studies with multiplicity control and clinically relevant cognitive outcomes are required.

]]> Longitudinal SPECT Assessment of Regional Cerebral Perfusion Associated with Nicergoline Use in Parkinson’s Disease Without Dementia: An Exploratory Observational Study Byungseok Kim Seung-Hee Na In-Uk Song Yong-An Chung doi: 10.3390/diagnostics16223726 Diagnostics 2026-11-11 Diagnostics 2026-11-11 16 22 Article 3726 10.3390/diagnostics16223726 https://www.mdpi.com/2075-4418/16/22/3726 Diagnostics, Vol. 16, Pages 3725: A Source-Traced PET/CT Scanner Performance Database (2004–2024): The Sphere-Size Dependence of Time-of-Flight Contrast Recovery https://www.mdpi.com/2075-4418/16/22/3725 Background: Small-lesion quantification is a key task in diagnostic PET/CT. However, published performance data span two decades and multiple NEMA NU 2 revisions, complicating comparisons. We developed a source-traced database to examine how reconstruction-associated improvements in hot-sphere contrast recovery vary with sphere diameter, providing reference data for phantom-based protocol optimisation. Methods: Published NEMA and phantom measurements were source-verified, linked to scanner geometry, and annotated with acquisition and reconstruction conditions. Contrast recovery at a 4:1 sphere-to-background activity ratio (151 measurements; 13 scanners) was analysed using mixed-effects meta-regression with a scanner random intercept. Results: The database included 28 scanner models (2004–2024), 610 measurements and 43 publications. Descriptively, sensitivity was 3.8–10.9 cps/kBq for lutetium-based analogue scanners, 12.1–47.6 for conventional-geometry digital scanners and 176–192 for total-body scanners. Time of flight (TOF) was associated with a 7.9-percentage-point-higher contrast recovery (95% CI 4.8 to 11.1), but the association varied with sphere diameter (p < 0.001) and was significant only at 10–17 mm (11.4, 9.9 and 7.0 points); estimates at 28 and 37 mm rested on four to five scanners and were imprecise. The median between-laboratory difference under matched conditions was 5.7 points. Point-spread-function and regularised-reconstruction effects were not robust. Conclusions: In phantom measurements, TOF-associated gains were concentrated at 10–17 mm. These data provide reference values for phantom-based protocol optimisation, harmonisation and acceptance testing; they do not measure lesion detectability or diagnostic accuracy, which require patient-based validation. 2026-11-11 Diagnostics, Vol. 16, Pages 3725: A Source-Traced PET/CT Scanner Performance Database (2004–2024): The Sphere-Size Dependence of Time-of-Flight Contrast Recovery

Diagnostics doi: 10.3390/diagnostics16223725

Authors: Rajeh Assiri Ibrahim Hadadi Mohammed Asiri Abdulaziz Yahya M. Hussain Hussein Alshaari Mohammad Sayed Mansour M. Alqahtani

Background: Small-lesion quantification is a key task in diagnostic PET/CT. However, published performance data span two decades and multiple NEMA NU 2 revisions, complicating comparisons. We developed a source-traced database to examine how reconstruction-associated improvements in hot-sphere contrast recovery vary with sphere diameter, providing reference data for phantom-based protocol optimisation. Methods: Published NEMA and phantom measurements were source-verified, linked to scanner geometry, and annotated with acquisition and reconstruction conditions. Contrast recovery at a 4:1 sphere-to-background activity ratio (151 measurements; 13 scanners) was analysed using mixed-effects meta-regression with a scanner random intercept. Results: The database included 28 scanner models (2004–2024), 610 measurements and 43 publications. Descriptively, sensitivity was 3.8–10.9 cps/kBq for lutetium-based analogue scanners, 12.1–47.6 for conventional-geometry digital scanners and 176–192 for total-body scanners. Time of flight (TOF) was associated with a 7.9-percentage-point-higher contrast recovery (95% CI 4.8 to 11.1), but the association varied with sphere diameter (p < 0.001) and was significant only at 10–17 mm (11.4, 9.9 and 7.0 points); estimates at 28 and 37 mm rested on four to five scanners and were imprecise. The median between-laboratory difference under matched conditions was 5.7 points. Point-spread-function and regularised-reconstruction effects were not robust. Conclusions: In phantom measurements, TOF-associated gains were concentrated at 10–17 mm. These data provide reference values for phantom-based protocol optimisation, harmonisation and acceptance testing; they do not measure lesion detectability or diagnostic accuracy, which require patient-based validation.

]]> A Source-Traced PET/CT Scanner Performance Database (2004–2024): The Sphere-Size Dependence of Time-of-Flight Contrast Recovery Rajeh Assiri Ibrahim Hadadi Mohammed Asiri Abdulaziz Yahya M. Hussain Hussein Alshaari Mohammad Sayed Mansour M. Alqahtani doi: 10.3390/diagnostics16223725 Diagnostics 2026-11-11 Diagnostics 2026-11-11 16 22 Article 3725 10.3390/diagnostics16223725 https://www.mdpi.com/2075-4418/16/22/3725 Diagnostics, Vol. 16, Pages 3724: Association Between Lateral-Incisor Morphology and Palatally Impacted Maxillary Canines: A Systematic Review and Meta-Analysis https://www.mdpi.com/2075-4418/16/22/3724 Maxillary lateral-incisor morphological variations have been associated with palatal maxillary canine impaction, although the nature and strength of this association remain unclear. Aims: To systematically evaluate and quantitatively synthesize the association between maxillary lateral-incisor morphology and palatal maxillary canine impaction. Materials and Methods: Four electronic databases were searched through April 2026 for observational studies comparing lateral-incisor morphology in patients with palatally impacted canines with external controls and/or contralateral non-impacted sides. Risk of bias was assessed using the Joanna Briggs Institute checklist. Random-effects meta-analyses were performed for sufficiently comparable external-control outcomes. Results: Thirty-five reports representing 34 studies were included, with 19 studies contributing to meta-analysis. Compared with external controls, lateral incisors in patients with palatal canine impaction were significantly narrower mesiodistally (MD −0.40 mm; 95% CI −0.51 to −0.29) and buccolingually (MD −0.53 mm; 95% CI −0.82 to −0.24). Peg-shaped lateral incisors showed the strongest association (OR 6.59; 95% CI 3.85–11.29), whereas root length did not differ significantly (MD −0.21 mm; 95% CI −0.58 to 0.16). Within-person comparisons showed little consistent difference in crown dimensions between affected and contralateral sides, although shorter roots and lower tooth volumes were more frequently observed adjacent to impacted canines. Conclusions: Palatal maxillary canine impaction is associated with smaller and more frequently peg-shaped lateral incisors. The greater differences observed between affected individuals and external controls, compared with those observed between sides within the same individual, suggest a broader developmental phenotype, although local interactions cannot be excluded. Lateral-incisor morphology may therefore serve as a clinical marker of increased susceptibility rather than an isolated diagnostic feature. 2026-11-11 Diagnostics, Vol. 16, Pages 3724: Association Between Lateral-Incisor Morphology and Palatally Impacted Maxillary Canines: A Systematic Review and Meta-Analysis

Diagnostics doi: 10.3390/diagnostics16223724

Authors: Alexa Nader Anthony T. Macari

Maxillary lateral-incisor morphological variations have been associated with palatal maxillary canine impaction, although the nature and strength of this association remain unclear. Aims: To systematically evaluate and quantitatively synthesize the association between maxillary lateral-incisor morphology and palatal maxillary canine impaction. Materials and Methods: Four electronic databases were searched through April 2026 for observational studies comparing lateral-incisor morphology in patients with palatally impacted canines with external controls and/or contralateral non-impacted sides. Risk of bias was assessed using the Joanna Briggs Institute checklist. Random-effects meta-analyses were performed for sufficiently comparable external-control outcomes. Results: Thirty-five reports representing 34 studies were included, with 19 studies contributing to meta-analysis. Compared with external controls, lateral incisors in patients with palatal canine impaction were significantly narrower mesiodistally (MD −0.40 mm; 95% CI −0.51 to −0.29) and buccolingually (MD −0.53 mm; 95% CI −0.82 to −0.24). Peg-shaped lateral incisors showed the strongest association (OR 6.59; 95% CI 3.85–11.29), whereas root length did not differ significantly (MD −0.21 mm; 95% CI −0.58 to 0.16). Within-person comparisons showed little consistent difference in crown dimensions between affected and contralateral sides, although shorter roots and lower tooth volumes were more frequently observed adjacent to impacted canines. Conclusions: Palatal maxillary canine impaction is associated with smaller and more frequently peg-shaped lateral incisors. The greater differences observed between affected individuals and external controls, compared with those observed between sides within the same individual, suggest a broader developmental phenotype, although local interactions cannot be excluded. Lateral-incisor morphology may therefore serve as a clinical marker of increased susceptibility rather than an isolated diagnostic feature.

]]> Association Between Lateral-Incisor Morphology and Palatally Impacted Maxillary Canines: A Systematic Review and Meta-Analysis Alexa Nader Anthony T. Macari doi: 10.3390/diagnostics16223724 Diagnostics 2026-11-11 Diagnostics 2026-11-11 16 22 Systematic Review 3724 10.3390/diagnostics16223724 https://www.mdpi.com/2075-4418/16/22/3724 Diagnostics, Vol. 16, Pages 3723: Body Size, Radiation Dose and Exposure Index in Conventional Radiography: A Multicentre Prospective Study https://www.mdpi.com/2075-4418/16/22/3723 Background/Objectives: Exposure index (EI) reflects detector exposure rather than patient dose, but its behaviour as patient size increases remains incompletely characterised across radiographic examinations. We evaluated continuous associations of body mass index (BMI) and regional body thickness proxy with dose–area product (DAP), entrance surface dose (ESD), and EI, and tested whether associations differed by examination and institution. Methods: This prospective multicentre observational study included 572 exposures from 331 adults undergoing nine projections at three institutions. Generalised estimating equations with a Gamma distribution and log link accounted for repeated exposures. Total-association models adjusted for examination, institution, age, and sex; technical-adjusted models additionally included log mAs and kVp, with SSD included only in BMI-based models. Results: In total-association models adjusted for examination, institution, age, and sex, each 1 kg/m2 increase in BMI was associated with 4.31% higher DAP, 3.25% higher estimated ESD, and 3.45% lower EI (all p < 0.001). Each 1 cm increase in geometrically derived regional-thickness proxy was associated with 3.03% higher DAP, 2.97% higher estimated ESD, and 2.51% lower EI (all p < 0.001). Technical adjustment substantially attenuated the associations with DAP, whereas inverse associations with EI persisted. Conclusions: Body-size associations were outcome- and examination-specific. Direct EI–dose associations were generally positive but substantially attenuated after accounting for exposure technique and regional thickness, indicating that their relationship is strongly influenced by patient attenuation and technical exposure factors. These findings support further examination- and system-specific evaluation of EI behaviour alongside body size, technical factors, and patient-dose indicators. 2026-11-11 Diagnostics, Vol. 16, Pages 3723: Body Size, Radiation Dose and Exposure Index in Conventional Radiography: A Multicentre Prospective Study

Diagnostics doi: 10.3390/diagnostics16223723

Authors: Manuel Duarte Lobo Sérgio Miravent Rui Pereira de Almeida

Background/Objectives: Exposure index (EI) reflects detector exposure rather than patient dose, but its behaviour as patient size increases remains incompletely characterised across radiographic examinations. We evaluated continuous associations of body mass index (BMI) and regional body thickness proxy with dose–area product (DAP), entrance surface dose (ESD), and EI, and tested whether associations differed by examination and institution. Methods: This prospective multicentre observational study included 572 exposures from 331 adults undergoing nine projections at three institutions. Generalised estimating equations with a Gamma distribution and log link accounted for repeated exposures. Total-association models adjusted for examination, institution, age, and sex; technical-adjusted models additionally included log mAs and kVp, with SSD included only in BMI-based models. Results: In total-association models adjusted for examination, institution, age, and sex, each 1 kg/m2 increase in BMI was associated with 4.31% higher DAP, 3.25% higher estimated ESD, and 3.45% lower EI (all p < 0.001). Each 1 cm increase in geometrically derived regional-thickness proxy was associated with 3.03% higher DAP, 2.97% higher estimated ESD, and 2.51% lower EI (all p < 0.001). Technical adjustment substantially attenuated the associations with DAP, whereas inverse associations with EI persisted. Conclusions: Body-size associations were outcome- and examination-specific. Direct EI–dose associations were generally positive but substantially attenuated after accounting for exposure technique and regional thickness, indicating that their relationship is strongly influenced by patient attenuation and technical exposure factors. These findings support further examination- and system-specific evaluation of EI behaviour alongside body size, technical factors, and patient-dose indicators.

]]> Body Size, Radiation Dose and Exposure Index in Conventional Radiography: A Multicentre Prospective Study Manuel Duarte Lobo Sérgio Miravent Rui Pereira de Almeida doi: 10.3390/diagnostics16223723 Diagnostics 2026-11-11 Diagnostics 2026-11-11 16 22 Article 3723 10.3390/diagnostics16223723 https://www.mdpi.com/2075-4418/16/22/3723 Diagnostics, Vol. 16, Pages 3722: Unexpected Immune Biomarker Separation by Recorded Long COVID Status in an Exploratory Cross-Sectional Study https://www.mdpi.com/2075-4418/16/22/3722 Background: Long COVID is clinically and immunologically heterogeneous. We describe unexpected biomarker separation between recorded groups and limitations that prevent a disease-specific interpretation. Methods: This exploratory cross-sectional secondary analysis included 191 post-COVID records: 158 labeled long COVID and 33 originally designated “No adverse events.” The comparator designation did not establish a clinically verified absence of post-COVID sequelae. Eight biomarkers were evaluated after correction of confirmed reporting errors at common assay lower limits. Analyses included rank-based comparisons, Firth penalized logistic regression, internal resampling, censoring sensitivity analyses and exploratory clustering. Results: Seven biomarkers were higher in the recorded long COVID group (all false-discovery-rate q < 0.001). Apparent areas under the receiver operating characteristic curve (AUCs) were 0.9942 for CXCL9 and 0.9914 for IL-6. The seven-marker model had an apparent AUC of 1.0000 and a mean cross-validated AUC of 0.9989. CXCL9 was at or below the reporting limit in 30/33 comparator records versus 1/158 long COVID records. All individual coefficients in the full model had 95% profile intervals including the null. Clustering did not establish distinct biological subtypes. Conclusions: The unexpectedly strong separation is a hypothesis-generating observation requiring independent investigation. Incomplete verification of group definitions and sampling times limits disease-specific interpretation. These findings do not establish a long COVID-specific immune signature or a clinically applicable diagnostic test. 2026-11-11 Diagnostics, Vol. 16, Pages 3722: Unexpected Immune Biomarker Separation by Recorded Long COVID Status in an Exploratory Cross-Sectional Study

Diagnostics doi: 10.3390/diagnostics16223722

Authors: Yuka Yamagishi Satoshi Takahashi Hiroyuki Kunishima Hiroshige Mikamo

Background: Long COVID is clinically and immunologically heterogeneous. We describe unexpected biomarker separation between recorded groups and limitations that prevent a disease-specific interpretation. Methods: This exploratory cross-sectional secondary analysis included 191 post-COVID records: 158 labeled long COVID and 33 originally designated “No adverse events.” The comparator designation did not establish a clinically verified absence of post-COVID sequelae. Eight biomarkers were evaluated after correction of confirmed reporting errors at common assay lower limits. Analyses included rank-based comparisons, Firth penalized logistic regression, internal resampling, censoring sensitivity analyses and exploratory clustering. Results: Seven biomarkers were higher in the recorded long COVID group (all false-discovery-rate q < 0.001). Apparent areas under the receiver operating characteristic curve (AUCs) were 0.9942 for CXCL9 and 0.9914 for IL-6. The seven-marker model had an apparent AUC of 1.0000 and a mean cross-validated AUC of 0.9989. CXCL9 was at or below the reporting limit in 30/33 comparator records versus 1/158 long COVID records. All individual coefficients in the full model had 95% profile intervals including the null. Clustering did not establish distinct biological subtypes. Conclusions: The unexpectedly strong separation is a hypothesis-generating observation requiring independent investigation. Incomplete verification of group definitions and sampling times limits disease-specific interpretation. These findings do not establish a long COVID-specific immune signature or a clinically applicable diagnostic test.

]]> Unexpected Immune Biomarker Separation by Recorded Long COVID Status in an Exploratory Cross-Sectional Study Yuka Yamagishi Satoshi Takahashi Hiroyuki Kunishima Hiroshige Mikamo doi: 10.3390/diagnostics16223722 Diagnostics 2026-11-11 Diagnostics 2026-11-11 16 22 Article 3722 10.3390/diagnostics16223722 https://www.mdpi.com/2075-4418/16/22/3722 Diagnostics, Vol. 16, Pages 3721: Anatomical Validity of MRI-Based Choroid Plexus Segmentation: Regional Boundaries, Age-Related Morphology, and Implications for Neuroimaging Biomarkers https://www.mdpi.com/2075-4418/16/22/3721 Magnetic resonance imaging (MRI)-derived choroid plexus (ChP) volume is increasingly investigated in studies of brain aging and neurodegeneration, yet its anatomical meaning remains uncertain because segmentation methods differ in ventricular coverage, image contrast, and reference annotations. This narrative review examines the anatomical basis and methodological validity of ChP volumetry by integrating evidence on ventricular anatomy, age-related tissue changes, manual and automated segmentation, and associations with cognitive impairment and Alzheimer’s disease. The lateral ventricular ChP, particularly the atrial glomus, is generally easier to delineate on conventional MRI than its thin extensions and the third and fourth ventricular components. Segmentation performance depends on the anatomical reference and acquisition protocol; agreement with manually drawn masks does not necessarily establish complete anatomical coverage. In addition, age-related vascular remodeling, changes in stromal composition, calcification, and cystic alterations can affect MRI appearance and the interpretation of total volume. Although ChP enlargement has been associated with aging, cognitive impairment, and Alzheimer’s disease, volume alone cannot identify the contributing tissue compartments or establish blood–cerebrospinal fluid barrier dysfunction. We propose an anatomy-centered approach to ChP volumetry based on explicit regional definitions, complementary measures of spatial and volumetric accuracy, assessment of test–retest and multicenter reliability, and independent biological validation when functional interpretations are intended. 2026-11-11 Diagnostics, Vol. 16, Pages 3721: Anatomical Validity of MRI-Based Choroid Plexus Segmentation: Regional Boundaries, Age-Related Morphology, and Implications for Neuroimaging Biomarkers

Diagnostics doi: 10.3390/diagnostics16223721

Authors: Michele Cerasuolo Francesco Spada Umberto Galdiero Nicholas Giulio Raccagni Simone Laguardia Gary Antonio Barahona Rodriguez

Magnetic resonance imaging (MRI)-derived choroid plexus (ChP) volume is increasingly investigated in studies of brain aging and neurodegeneration, yet its anatomical meaning remains uncertain because segmentation methods differ in ventricular coverage, image contrast, and reference annotations. This narrative review examines the anatomical basis and methodological validity of ChP volumetry by integrating evidence on ventricular anatomy, age-related tissue changes, manual and automated segmentation, and associations with cognitive impairment and Alzheimer’s disease. The lateral ventricular ChP, particularly the atrial glomus, is generally easier to delineate on conventional MRI than its thin extensions and the third and fourth ventricular components. Segmentation performance depends on the anatomical reference and acquisition protocol; agreement with manually drawn masks does not necessarily establish complete anatomical coverage. In addition, age-related vascular remodeling, changes in stromal composition, calcification, and cystic alterations can affect MRI appearance and the interpretation of total volume. Although ChP enlargement has been associated with aging, cognitive impairment, and Alzheimer’s disease, volume alone cannot identify the contributing tissue compartments or establish blood–cerebrospinal fluid barrier dysfunction. We propose an anatomy-centered approach to ChP volumetry based on explicit regional definitions, complementary measures of spatial and volumetric accuracy, assessment of test–retest and multicenter reliability, and independent biological validation when functional interpretations are intended.

]]> Anatomical Validity of MRI-Based Choroid Plexus Segmentation: Regional Boundaries, Age-Related Morphology, and Implications for Neuroimaging Biomarkers Michele Cerasuolo Francesco Spada Umberto Galdiero Nicholas Giulio Raccagni Simone Laguardia Gary Antonio Barahona Rodriguez doi: 10.3390/diagnostics16223721 Diagnostics 2026-11-11 Diagnostics 2026-11-11 16 22 Review 3721 10.3390/diagnostics16223721 https://www.mdpi.com/2075-4418/16/22/3721 Diagnostics, Vol. 16, Pages 3720: Prosthodontic Identification in Forensic Diagnostics: From Conventional Marking to Digital Traceability and AI-Assisted Recognition—A Narrative Review https://www.mdpi.com/2075-4418/16/22/3720 Human identification is a central component of medico-legal investigations and disaster victim identification (DVI), particularly when remains are decomposed, burned, fragmented, or skeletonized. Dental tissues, restorations, and prosthetic appliances may preserve patient-specific information under conditions that compromise other identifying features. This narrative review aimed to examine conventional and digital prosthodontic identification and traceability approaches and to evaluate their potential applications in forensic diagnostics and human identification. A structured search of PubMed, Scopus, Web of Science, and Google Scholar identified publications from January 2000 to August 2026 on prosthodontic identification, digital traceability, AI-assisted implant recognition, blockchain-based dental data management, and complementary oral biometric methods. Records were independently screened by two authors according to predefined eligibility criteria. Of the 1446 records identified, 558 duplicates were removed, and 92 studies were included in the final narrative synthesis. The evidence was synthesized thematically according to the identification or traceability approach. Conventional methods remain simple and accessible but show variable durability and readability, whereas digital and electronic systems offer greater information capacity and retrievability but are limited by technical requirements and incomplete forensic validation. In a 20 min thermal-exposure experiment, acrylic resin blocks were largely destroyed at 800 °C, whereas some metallic identification labels remained readable at 800–1000 °C, with material-dependent differences in preservation and readability among metallic labels at 1200 °C. These findings represent study-specific observations rather than universal thermal resistance thresholds. Digital imaging, intraoral scanning, CAD/CAM records, AI-assisted implant recognition, and blockchain-supported systems further expand traceability, although the overall evidence remains heterogeneous. Prosthodontic identification and traceability encompass complementary conventional and digital approaches rather than a single universally applicable method, while oral biometrics serve only as adjunctive evidence and cannot independently establish identity. Their forensic value depends on durability, retrievability, availability of corresponding antemortem information, interoperability, and appropriate management of sensitive patient data. Further standardized and clinically relevant validation is needed before advanced traceability systems can be routinely incorporated into forensic identification workflows. 2026-11-11 Diagnostics, Vol. 16, Pages 3720: Prosthodontic Identification in Forensic Diagnostics: From Conventional Marking to Digital Traceability and AI-Assisted Recognition—A Narrative Review

Diagnostics doi: 10.3390/diagnostics16223720

Authors: Rabia Çiçek Gizem Yılmaz Medine Çiçek

Human identification is a central component of medico-legal investigations and disaster victim identification (DVI), particularly when remains are decomposed, burned, fragmented, or skeletonized. Dental tissues, restorations, and prosthetic appliances may preserve patient-specific information under conditions that compromise other identifying features. This narrative review aimed to examine conventional and digital prosthodontic identification and traceability approaches and to evaluate their potential applications in forensic diagnostics and human identification. A structured search of PubMed, Scopus, Web of Science, and Google Scholar identified publications from January 2000 to August 2026 on prosthodontic identification, digital traceability, AI-assisted implant recognition, blockchain-based dental data management, and complementary oral biometric methods. Records were independently screened by two authors according to predefined eligibility criteria. Of the 1446 records identified, 558 duplicates were removed, and 92 studies were included in the final narrative synthesis. The evidence was synthesized thematically according to the identification or traceability approach. Conventional methods remain simple and accessible but show variable durability and readability, whereas digital and electronic systems offer greater information capacity and retrievability but are limited by technical requirements and incomplete forensic validation. In a 20 min thermal-exposure experiment, acrylic resin blocks were largely destroyed at 800 °C, whereas some metallic identification labels remained readable at 800–1000 °C, with material-dependent differences in preservation and readability among metallic labels at 1200 °C. These findings represent study-specific observations rather than universal thermal resistance thresholds. Digital imaging, intraoral scanning, CAD/CAM records, AI-assisted implant recognition, and blockchain-supported systems further expand traceability, although the overall evidence remains heterogeneous. Prosthodontic identification and traceability encompass complementary conventional and digital approaches rather than a single universally applicable method, while oral biometrics serve only as adjunctive evidence and cannot independently establish identity. Their forensic value depends on durability, retrievability, availability of corresponding antemortem information, interoperability, and appropriate management of sensitive patient data. Further standardized and clinically relevant validation is needed before advanced traceability systems can be routinely incorporated into forensic identification workflows.

]]> Prosthodontic Identification in Forensic Diagnostics: From Conventional Marking to Digital Traceability and AI-Assisted Recognition—A Narrative Review Rabia Çiçek Gizem Yılmaz Medine Çiçek doi: 10.3390/diagnostics16223720 Diagnostics 2026-11-11 Diagnostics 2026-11-11 16 22 Review 3720 10.3390/diagnostics16223720 https://www.mdpi.com/2075-4418/16/22/3720 Diagnostics, Vol. 16, Pages 3717: Machine-Learning-Assisted Detection of Residual or Recurrent Filling in Endovascularly Treated Intracranial Aneurysms on TOF-MRA: A Pilot Study https://www.mdpi.com/2075-4418/16/22/3717 Background and Purpose: Surveillance TOF-MRA is a non-invasive alternative to digital subtraction angiography (DSA) for detecting aneurysm residual/recurrence after endovascular embolization but is limited by coil/WEB device-related susceptibility artifact and inter-reader variability. We evaluated a supervised machine-learning classifier for detecting residuals and/or recurrence on surveillance TOF-MRA obtained 3–6 months after endovascular embolization, referenced against the Raymond–Roy Occlusion Classification (RROC) class assigned on the surveillance TOF-MRA itself by a single, non-blinded neuroradiologist who had access to the completion DSA and 24–48 h post-procedural MRA. Materials and Methods: In this single-center retrospective pilot study, 53 of 55 eligible adults with intrasaccular endovascular embolization (coiling or WEB device, 2020–2024) were analyzed after excluding 2 for suboptimal MRA quality (RROC I: n = 13, II: n = 18, III: n = 27); the final analytical cohort comprised 58 aneurysms from 53 unique patients. Radiomic features from a class-agnostic 3 mm peri-device region were extracted with PyRadiomics and evaluated using L1-regularized logistic regression, calibrated linear SVM, and random forest. Model evaluation used 100 repetitions of 5-fold patient-grouped nested cross-validation, with all aneurysms from the same patient kept within the same fold and preprocessing, feature selection, hyperparameter tuning, and model fitting confined to training data. A post hoc exploratory subgroup analysis excluded the morphologically intermediate Class II cases. Results: In the primary analysis of 58 aneurysms from 53 patients, L1-regularized logistic regression yielded an aggregated repeated out-of-fold AUC of 0.716 (95% patient-cluster bootstrap CI 0.566–0.856), sensitivity 0.800, specificity 0.462, negative predictive value 0.400, and balanced accuracy 0.631 at a 0.50 threshold. The mean AUC across the 100 individual cross-validation repetitions, which is a different estimate, was 0.601 (SD 0.088) for logistic regression, 0.631 (SD 0.056) for random forest and 0.555 (SD 0.097) for the calibrated linear SVM. In the post hoc exploratory Class I versus III analysis (40 aneurysms from 38 patients), L1 logistic regression yielded AUC 0.832 (95% CI 0.704–0.946), sensitivity 0.852, specificity 0.692, and balanced accuracy 0.772. The subgroup represents a different, more separated classification task and is not directly comparable with the full cohort. Of 45 outcome-positive aneurysms, 42% were persistent residual filling and 58% interval recurrence. Conclusions: This pilot analysis demonstrates the technical feasibility of the patient-grouped radiomics-based classification of post-treatment surveillance TOF-MRA. The performance estimates remain preliminary because of the small single-center cohort, limited number of negative cases, scanner/device heterogeneity, and absence of external validation. The exploratory Class I versus III results should not be interpreted as evidence of improved clinical performance and warrant external multicenter validation. The specificity and negative predictive value were low, the incremental value of radiomics beyond simpler device- or morphology-based approaches has not been established, and the model is not ready for clinical use. 2026-11-11 Diagnostics, Vol. 16, Pages 3717: Machine-Learning-Assisted Detection of Residual or Recurrent Filling in Endovascularly Treated Intracranial Aneurysms on TOF-MRA: A Pilot Study

Diagnostics doi: 10.3390/diagnostics16223717

Authors: Sushmitha Puttappa Shivagange Augusto da Mota Goncalves Filho Mohamed S. Hefny Eduardo Portela de Oliveira

Background and Purpose: Surveillance TOF-MRA is a non-invasive alternative to digital subtraction angiography (DSA) for detecting aneurysm residual/recurrence after endovascular embolization but is limited by coil/WEB device-related susceptibility artifact and inter-reader variability. We evaluated a supervised machine-learning classifier for detecting residuals and/or recurrence on surveillance TOF-MRA obtained 3–6 months after endovascular embolization, referenced against the Raymond–Roy Occlusion Classification (RROC) class assigned on the surveillance TOF-MRA itself by a single, non-blinded neuroradiologist who had access to the completion DSA and 24–48 h post-procedural MRA. Materials and Methods: In this single-center retrospective pilot study, 53 of 55 eligible adults with intrasaccular endovascular embolization (coiling or WEB device, 2020–2024) were analyzed after excluding 2 for suboptimal MRA quality (RROC I: n = 13, II: n = 18, III: n = 27); the final analytical cohort comprised 58 aneurysms from 53 unique patients. Radiomic features from a class-agnostic 3 mm peri-device region were extracted with PyRadiomics and evaluated using L1-regularized logistic regression, calibrated linear SVM, and random forest. Model evaluation used 100 repetitions of 5-fold patient-grouped nested cross-validation, with all aneurysms from the same patient kept within the same fold and preprocessing, feature selection, hyperparameter tuning, and model fitting confined to training data. A post hoc exploratory subgroup analysis excluded the morphologically intermediate Class II cases. Results: In the primary analysis of 58 aneurysms from 53 patients, L1-regularized logistic regression yielded an aggregated repeated out-of-fold AUC of 0.716 (95% patient-cluster bootstrap CI 0.566–0.856), sensitivity 0.800, specificity 0.462, negative predictive value 0.400, and balanced accuracy 0.631 at a 0.50 threshold. The mean AUC across the 100 individual cross-validation repetitions, which is a different estimate, was 0.601 (SD 0.088) for logistic regression, 0.631 (SD 0.056) for random forest and 0.555 (SD 0.097) for the calibrated linear SVM. In the post hoc exploratory Class I versus III analysis (40 aneurysms from 38 patients), L1 logistic regression yielded AUC 0.832 (95% CI 0.704–0.946), sensitivity 0.852, specificity 0.692, and balanced accuracy 0.772. The subgroup represents a different, more separated classification task and is not directly comparable with the full cohort. Of 45 outcome-positive aneurysms, 42% were persistent residual filling and 58% interval recurrence. Conclusions: This pilot analysis demonstrates the technical feasibility of the patient-grouped radiomics-based classification of post-treatment surveillance TOF-MRA. The performance estimates remain preliminary because of the small single-center cohort, limited number of negative cases, scanner/device heterogeneity, and absence of external validation. The exploratory Class I versus III results should not be interpreted as evidence of improved clinical performance and warrant external multicenter validation. The specificity and negative predictive value were low, the incremental value of radiomics beyond simpler device- or morphology-based approaches has not been established, and the model is not ready for clinical use.

]]> Machine-Learning-Assisted Detection of Residual or Recurrent Filling in Endovascularly Treated Intracranial Aneurysms on TOF-MRA: A Pilot Study Sushmitha Puttappa Shivagange Augusto da Mota Goncalves Filho Mohamed S. Hefny Eduardo Portela de Oliveira doi: 10.3390/diagnostics16223717 Diagnostics 2026-11-11 Diagnostics 2026-11-11 16 22 Article 3717 10.3390/diagnostics16223717 https://www.mdpi.com/2075-4418/16/22/3717 Diagnostics, Vol. 16, Pages 3719: Not All That Hurts Is Fibromyalgia: The Challenges of Differential Diagnosis of Patients Referred to a Tertiary Care Center https://www.mdpi.com/2075-4418/16/22/3719 Background/Objectives: Fibromyalgia (FM) is a complex and disabling condition characterized by chronic widespread pain, fatigue and multiple somatic symptoms, often overlapping with rheumatic (RMD) and non-rheumatic diseases. Since objective biomarkers are lacking, diagnosis relies on validated criteria and careful clinical assessment. This study aimed to describe a referral cohort including patients with either a previous diagnosis or suspicion of FM and to identify the proportion of patients fulfilling FM criteria, the severity of their FM, and to identify alternative or associated conditions. Methods: A prospective cohort of consecutive patients referred to our Center between June 2023 and October 2025 was assessed according to the 2016 American College of Rheumatology (ACR) diagnostic criteria for FM. Demographic data, medical history, and clinical findings were collected. Additional laboratory or imaging investigations were performed when clinically indicated. FM severity was evaluated using validated tools included in the 2016 ACR diagnostic criteria. Results: Overall, 247 patients were enrolled: 44 with a certified previous FM diagnosis, 145 referred by physicians for suspected FM and 58 self-referred. Among patients without a previous certified diagnosis, FM was newly diagnosed in 75% of physician-referred and 77% of self-referred patients. A substantial proportion was also diagnosed with an RMD. Longer symptom duration, higher fatigue and worse global health were associated with FM. Conclusions: Among patients who reached our referral center because of suspected FM, a high proportion fulfilled the 2016 ACR criteria. Careful application of FM criteria and evaluation of coexisting conditions may improve timely diagnosis and management. 2026-11-11 Diagnostics, Vol. 16, Pages 3719: Not All That Hurts Is Fibromyalgia: The Challenges of Differential Diagnosis of Patients Referred to a Tertiary Care Center

Diagnostics doi: 10.3390/diagnostics16223719

Authors: Francesco Carubbi Alessia Alunno Piera Altieri Maria Ester Carugno Deborah Colella Marianna Litterio Antonella Paolucci Claudio Ferri

Background/Objectives: Fibromyalgia (FM) is a complex and disabling condition characterized by chronic widespread pain, fatigue and multiple somatic symptoms, often overlapping with rheumatic (RMD) and non-rheumatic diseases. Since objective biomarkers are lacking, diagnosis relies on validated criteria and careful clinical assessment. This study aimed to describe a referral cohort including patients with either a previous diagnosis or suspicion of FM and to identify the proportion of patients fulfilling FM criteria, the severity of their FM, and to identify alternative or associated conditions. Methods: A prospective cohort of consecutive patients referred to our Center between June 2023 and October 2025 was assessed according to the 2016 American College of Rheumatology (ACR) diagnostic criteria for FM. Demographic data, medical history, and clinical findings were collected. Additional laboratory or imaging investigations were performed when clinically indicated. FM severity was evaluated using validated tools included in the 2016 ACR diagnostic criteria. Results: Overall, 247 patients were enrolled: 44 with a certified previous FM diagnosis, 145 referred by physicians for suspected FM and 58 self-referred. Among patients without a previous certified diagnosis, FM was newly diagnosed in 75% of physician-referred and 77% of self-referred patients. A substantial proportion was also diagnosed with an RMD. Longer symptom duration, higher fatigue and worse global health were associated with FM. Conclusions: Among patients who reached our referral center because of suspected FM, a high proportion fulfilled the 2016 ACR criteria. Careful application of FM criteria and evaluation of coexisting conditions may improve timely diagnosis and management.

]]> Not All That Hurts Is Fibromyalgia: The Challenges of Differential Diagnosis of Patients Referred to a Tertiary Care Center Francesco Carubbi Alessia Alunno Piera Altieri Maria Ester Carugno Deborah Colella Marianna Litterio Antonella Paolucci Claudio Ferri doi: 10.3390/diagnostics16223719 Diagnostics 2026-11-11 Diagnostics 2026-11-11 16 22 Article 3719 10.3390/diagnostics16223719 https://www.mdpi.com/2075-4418/16/22/3719 Diagnostics, Vol. 16, Pages 3718: Correction: Eyiol et al. Diagnostic Performance and Trending Ability of Continuous Non-Invasive Hemoglobin Monitoring During Elective Intracranial Neurosurgery with Invasive Arterial Monitoring: Influence of Anesthetic Technique. Diagnostics 2026, 16, 673 https://www.mdpi.com/2075-4418/16/22/3718 Bahar Oc and Ates Duman were inadvertently omitted from the author list in the original publication [...] 2026-11-11 Diagnostics, Vol. 16, Pages 3718: Correction: Eyiol et al. Diagnostic Performance and Trending Ability of Continuous Non-Invasive Hemoglobin Monitoring During Elective Intracranial Neurosurgery with Invasive Arterial Monitoring: Influence of Anesthetic Technique. Diagnostics 2026, 16, 673

Diagnostics doi: 10.3390/diagnostics16223718

Authors: Hatice Eyiol Bahar Oc Ates Duman Oguzhan Arun

Bahar Oc and Ates Duman were inadvertently omitted from the author list in the original publication [...]

]]> Correction: Eyiol et al. Diagnostic Performance and Trending Ability of Continuous Non-Invasive Hemoglobin Monitoring During Elective Intracranial Neurosurgery with Invasive Arterial Monitoring: Influence of Anesthetic Technique. Diagnostics 2026, 16, 673 Hatice Eyiol Bahar Oc Ates Duman Oguzhan Arun doi: 10.3390/diagnostics16223718 Diagnostics 2026-11-11 Diagnostics 2026-11-11 16 22 Correction 3718 10.3390/diagnostics16223718 https://www.mdpi.com/2075-4418/16/22/3718 Diagnostics, Vol. 16, Pages 3716: Maternal Cardiovascular Phenotyping in Fetal Growth Restriction: Integrating Hemodynamics, Echocardiography, Circulating Biomarkers and Fetoplacental Doppler Assessment https://www.mdpi.com/2075-4418/16/22/3716 Background/Objectives: Fetal growth restriction (FGR) is associated with maternal cardiovascular maladaptation, but its relationship with cardiac function, biomarkers and fetoplacental dysfunction remains incompletely characterized. We aimed to characterize the maternal cardiovascular phenotype associated with FGR and its variation according to onset. Methods: This prospective study included 140 singleton pregnancies: 59 with FGR (10 early-onset; 49 late-onset) and 81 controls. Assessments included maternal hemodynamics, echocardiography, circulating biomarkers, fetoplacental Doppler indices and neonatal outcomes. Analyses comprised group comparisons, multivariable regression, correlations and exploratory biomarker ROC analyses. Results: After adjustment for gestational age at the corresponding assessment, maternal age, body mass index, preeclampsia and chronic hypertension, FGR was associated with lower cardiac output (−1.84 L/min; 95% CI, −2.13 to −1.55), higher systemic vascular resistance (+530 dyn·s·cm−5; 95% CI, 429–632) and altered relaxation indices. NT-proBNP and GDF-15 concentrations were 191% (95% CI, 141–250%) and 125% (95% CI, 92–164%) higher, respectively. Early-onset FGR showed greater abnormalities in selected hemodynamic and relaxation parameters and higher GDF-15 than late-onset FGR; e′, E/e′, and NT-proBNP did not differ significantly. Apparent within-cohort AUCs for FGR discrimination were 0.991 for NT-proBNP and 0.961 for GDF-15. Selected cardiovascular parameters correlated with fetoplacental Doppler indices and perinatal outcomes. Early-onset FGR had the highest NICU admission rate and longest neonatal hospitalization among survivors, alongside substantially earlier delivery. Conclusions: FGR was associated with a low-output, high-resistance maternal cardiovascular phenotype and elevated biomarkers. Onset-related comparisons remain exploratory and were not validated by the gestational-age-restricted sensitivity analysis, which included only late-onset FGR. Incremental predictive value beyond fetal biometry and Doppler assessment and benefits for clinical management remain to be established. 2026-11-11 Diagnostics, Vol. 16, Pages 3716: Maternal Cardiovascular Phenotyping in Fetal Growth Restriction: Integrating Hemodynamics, Echocardiography, Circulating Biomarkers and Fetoplacental Doppler Assessment

Diagnostics doi: 10.3390/diagnostics16223716

Authors: Dorina-Adelina Minciuna Mihai Stefan Cristian Haba Raluca-Maria Haba Cosmin-Daniel Minciuna Alexandru Carauleanu Ioana-Sadiye Scripcariu Cristina Cecati Monica Hancianu Daniela-Cristina Dimitriu Demetra-Gabriela Socolov

Background/Objectives: Fetal growth restriction (FGR) is associated with maternal cardiovascular maladaptation, but its relationship with cardiac function, biomarkers and fetoplacental dysfunction remains incompletely characterized. We aimed to characterize the maternal cardiovascular phenotype associated with FGR and its variation according to onset. Methods: This prospective study included 140 singleton pregnancies: 59 with FGR (10 early-onset; 49 late-onset) and 81 controls. Assessments included maternal hemodynamics, echocardiography, circulating biomarkers, fetoplacental Doppler indices and neonatal outcomes. Analyses comprised group comparisons, multivariable regression, correlations and exploratory biomarker ROC analyses. Results: After adjustment for gestational age at the corresponding assessment, maternal age, body mass index, preeclampsia and chronic hypertension, FGR was associated with lower cardiac output (−1.84 L/min; 95% CI, −2.13 to −1.55), higher systemic vascular resistance (+530 dyn·s·cm−5; 95% CI, 429–632) and altered relaxation indices. NT-proBNP and GDF-15 concentrations were 191% (95% CI, 141–250%) and 125% (95% CI, 92–164%) higher, respectively. Early-onset FGR showed greater abnormalities in selected hemodynamic and relaxation parameters and higher GDF-15 than late-onset FGR; e′, E/e′, and NT-proBNP did not differ significantly. Apparent within-cohort AUCs for FGR discrimination were 0.991 for NT-proBNP and 0.961 for GDF-15. Selected cardiovascular parameters correlated with fetoplacental Doppler indices and perinatal outcomes. Early-onset FGR had the highest NICU admission rate and longest neonatal hospitalization among survivors, alongside substantially earlier delivery. Conclusions: FGR was associated with a low-output, high-resistance maternal cardiovascular phenotype and elevated biomarkers. Onset-related comparisons remain exploratory and were not validated by the gestational-age-restricted sensitivity analysis, which included only late-onset FGR. Incremental predictive value beyond fetal biometry and Doppler assessment and benefits for clinical management remain to be established.

]]> Maternal Cardiovascular Phenotyping in Fetal Growth Restriction: Integrating Hemodynamics, Echocardiography, Circulating Biomarkers and Fetoplacental Doppler Assessment Dorina-Adelina Minciuna Mihai Stefan Cristian Haba Raluca-Maria Haba Cosmin-Daniel Minciuna Alexandru Carauleanu Ioana-Sadiye Scripcariu Cristina Cecati Monica Hancianu Daniela-Cristina Dimitriu Demetra-Gabriela Socolov doi: 10.3390/diagnostics16223716 Diagnostics 2026-11-11 Diagnostics 2026-11-11 16 22 Article 3716 10.3390/diagnostics16223716 https://www.mdpi.com/2075-4418/16/22/3716 Diagnostics, Vol. 16, Pages 3715: Fetal Ventriculomegaly Across the Severity Spectrum: Prenatal Ultrasound Features, Longitudinal Evolution, and Additional Fetal MRI Findings https://www.mdpi.com/2075-4418/16/22/3715 Background/Objectives: Fetal ventriculomegaly is a heterogeneous prenatal finding with variable severity, evolution, and risk of associated cerebral abnormalities. Prenatal ultrasound is the primary diagnostic and follow-up modality, while fetal magnetic resonance imaging (MRI) may provide additional anatomical information. This study evaluated ultrasound features and longitudinal evolution across the ventriculomegaly severity spectrum and investigated prenatal features associated with additional MRI abnormalities. Methods: This single-center observational cohort included 62 fetuses who underwent detailed prenatal ultrasound, fetal MRI, and serial ultrasound follow-up. Ventriculomegaly was classified as mild (10–12 mm), moderate (>12–15 mm), or severe (>15 mm). Multivariable logistic regression assessed prenatal features associated with additional MRI abnormalities, and receiver operating characteristic analysis evaluated its discriminatory performance. Results: Mild, moderate, and severe ventriculomegaly were present in 12 (19.4%), 22 (35.5%), and 28 (45.2%) fetuses. Additional MRI abnormalities increased with severity (16.7%, 40.9%, and 71.4%; p = 0.004). Longitudinal evolution differed across severity groups (Fisher’s exact test, p = 0.013), with progression observed in 25.0%, 45.5%, and 71.4% of mild, moderate, and severe cases, respectively. Greater ultrasound ventricular diameter (OR 1.19 per 1 mm increase, 95% CI 1.03–1.37; p = 0.021) and bilateral asymmetric ventriculomegaly (OR 3.82, 95% CI 1.04–13.96; p = 0.043) were independently associated with additional MRI abnormalities. Ventricular diameter showed moderate discriminatory performance (AUC 0.768, 95% CI 0.651–0.886); an exploratory, data-derived 13.5 mm threshold yielded 83.9% sensitivity and 54.8% specificity. Conclusions: Increasing ventricular severity was associated with more frequent progression and additional MRI abnormalities. The associations of ventricular diameter and bilateral asymmetric ventriculomegaly with additional MRI abnormalities should be considered exploratory and require further validation. The identification of additional abnormalities even in mild cases supports the complementary role of fetal MRI alongside longitudinal ultrasound assessment. 2026-11-10 Diagnostics, Vol. 16, Pages 3715: Fetal Ventriculomegaly Across the Severity Spectrum: Prenatal Ultrasound Features, Longitudinal Evolution, and Additional Fetal MRI Findings

Diagnostics doi: 10.3390/diagnostics16223715

Authors: Raluca-Maria Haba Alexandru Carauleanu Mihai Stefan Cristian Haba Dorina-Adelina Minciuna Ioana-Sadiye Scripcariu Vasile Adrian Sescu Iustina Petra Solomon Condriuc Danisia Haba Dragos Negru Demetra-Gabriela Socolov

Background/Objectives: Fetal ventriculomegaly is a heterogeneous prenatal finding with variable severity, evolution, and risk of associated cerebral abnormalities. Prenatal ultrasound is the primary diagnostic and follow-up modality, while fetal magnetic resonance imaging (MRI) may provide additional anatomical information. This study evaluated ultrasound features and longitudinal evolution across the ventriculomegaly severity spectrum and investigated prenatal features associated with additional MRI abnormalities. Methods: This single-center observational cohort included 62 fetuses who underwent detailed prenatal ultrasound, fetal MRI, and serial ultrasound follow-up. Ventriculomegaly was classified as mild (10–12 mm), moderate (>12–15 mm), or severe (>15 mm). Multivariable logistic regression assessed prenatal features associated with additional MRI abnormalities, and receiver operating characteristic analysis evaluated its discriminatory performance. Results: Mild, moderate, and severe ventriculomegaly were present in 12 (19.4%), 22 (35.5%), and 28 (45.2%) fetuses. Additional MRI abnormalities increased with severity (16.7%, 40.9%, and 71.4%; p = 0.004). Longitudinal evolution differed across severity groups (Fisher’s exact test, p = 0.013), with progression observed in 25.0%, 45.5%, and 71.4% of mild, moderate, and severe cases, respectively. Greater ultrasound ventricular diameter (OR 1.19 per 1 mm increase, 95% CI 1.03–1.37; p = 0.021) and bilateral asymmetric ventriculomegaly (OR 3.82, 95% CI 1.04–13.96; p = 0.043) were independently associated with additional MRI abnormalities. Ventricular diameter showed moderate discriminatory performance (AUC 0.768, 95% CI 0.651–0.886); an exploratory, data-derived 13.5 mm threshold yielded 83.9% sensitivity and 54.8% specificity. Conclusions: Increasing ventricular severity was associated with more frequent progression and additional MRI abnormalities. The associations of ventricular diameter and bilateral asymmetric ventriculomegaly with additional MRI abnormalities should be considered exploratory and require further validation. The identification of additional abnormalities even in mild cases supports the complementary role of fetal MRI alongside longitudinal ultrasound assessment.

]]> Fetal Ventriculomegaly Across the Severity Spectrum: Prenatal Ultrasound Features, Longitudinal Evolution, and Additional Fetal MRI Findings Raluca-Maria Haba Alexandru Carauleanu Mihai Stefan Cristian Haba Dorina-Adelina Minciuna Ioana-Sadiye Scripcariu Vasile Adrian Sescu Iustina Petra Solomon Condriuc Danisia Haba Dragos Negru Demetra-Gabriela Socolov doi: 10.3390/diagnostics16223715 Diagnostics 2026-11-10 Diagnostics 2026-11-10 16 22 Article 3715 10.3390/diagnostics16223715 https://www.mdpi.com/2075-4418/16/22/3715 Diagnostics, Vol. 16, Pages 3714: Development and Internal Validation of a Nurse-Led Sepsis Risk Score Using AI-Enabled Remote Patient Monitoring Data in Adult Febrile Neutropenia: A Nested Case–Control Study https://www.mdpi.com/2075-4418/16/22/3714 Background/Objectives: Febrile neutropenia (FN) in hematologic malignancies carries a high risk of sepsis. We developed a regression model and a simplified nurse-led sepsis risk score using artificial intelligence (AI)-enabled remote patient monitoring (RPM) measurements and routine clinical and laboratory variables. Methods: A nested case–control study included 120 adult FN episodes (40 Sepsis-3-defined cases within 14 days of FN onset; 80 matched controls) in a hematology/bone marrow transplantation unit (BMT) in India (December 2021–December 2024). Heart rate and respiratory rate were obtained by ballistocardiography; blood pressure (BP), peripheral oxygen saturation (SpO2), and temperature were obtained using connected probes. Only a single set of FN-onset measurements was analyzed; longitudinal RPM trends and platform-generated alerts were excluded. Conditional logistic regression identified independent predictors and supplied coefficients for an integer-weighted score. Regression-model validation used two 1000-resample bootstrap analyses: one holding cut-offs and predictors fixed, the other repeating cut-off determination and backward selection. Integer-score discrimination was assessed separately. Results: Six predictors—tachycardia, hypotension, ≥2 comorbidities, absolute neutrophil count <99.5 cells/μL, chills, and elevated procalcitonin—formed an 8-point score. The regression model area under the receiver operating characteristic curve (AUC) was 0.847, with fixed-specification optimism of 0.028 and a corrected AUC of 0.819. Repeating cut-off determination and predictor selection yielded an apparent AUC of 0.855, optimism of 0.036, and corrected AUC of 0.819. The integer-score apparent AUC was 0.654 (95% CI 0.567–0.740), without optimism correction. Conclusions: Regression-model discrimination remained similar after accounting for cut-off determination and predictor selection. Integer-score performance remains uncorrected for optimism and requires independent temporal validation before clinical use. RPM’s AI functions and continuous-monitoring benefits were not evaluated. Temporal validation is planned in Phase II. Trial registration: Clinical Trials Registry of India (CTRI/2025/06/088290). 2026-11-10 Diagnostics, Vol. 16, Pages 3714: Development and Internal Validation of a Nurse-Led Sepsis Risk Score Using AI-Enabled Remote Patient Monitoring Data in Adult Febrile Neutropenia: A Nested Case–Control Study

Diagnostics doi: 10.3390/diagnostics16223714

Authors: Aswathy Asokan Ajee Kurunjippadath Lakshmanan Sachin Suresh Jadhav Nancy Dias Premjith Bhavukam Renjitha Bhaskaran Kaippaplakal Thamikkutty Moly

Background/Objectives: Febrile neutropenia (FN) in hematologic malignancies carries a high risk of sepsis. We developed a regression model and a simplified nurse-led sepsis risk score using artificial intelligence (AI)-enabled remote patient monitoring (RPM) measurements and routine clinical and laboratory variables. Methods: A nested case–control study included 120 adult FN episodes (40 Sepsis-3-defined cases within 14 days of FN onset; 80 matched controls) in a hematology/bone marrow transplantation unit (BMT) in India (December 2021–December 2024). Heart rate and respiratory rate were obtained by ballistocardiography; blood pressure (BP), peripheral oxygen saturation (SpO2), and temperature were obtained using connected probes. Only a single set of FN-onset measurements was analyzed; longitudinal RPM trends and platform-generated alerts were excluded. Conditional logistic regression identified independent predictors and supplied coefficients for an integer-weighted score. Regression-model validation used two 1000-resample bootstrap analyses: one holding cut-offs and predictors fixed, the other repeating cut-off determination and backward selection. Integer-score discrimination was assessed separately. Results: Six predictors—tachycardia, hypotension, ≥2 comorbidities, absolute neutrophil count <99.5 cells/μL, chills, and elevated procalcitonin—formed an 8-point score. The regression model area under the receiver operating characteristic curve (AUC) was 0.847, with fixed-specification optimism of 0.028 and a corrected AUC of 0.819. Repeating cut-off determination and predictor selection yielded an apparent AUC of 0.855, optimism of 0.036, and corrected AUC of 0.819. The integer-score apparent AUC was 0.654 (95% CI 0.567–0.740), without optimism correction. Conclusions: Regression-model discrimination remained similar after accounting for cut-off determination and predictor selection. Integer-score performance remains uncorrected for optimism and requires independent temporal validation before clinical use. RPM’s AI functions and continuous-monitoring benefits were not evaluated. Temporal validation is planned in Phase II. Trial registration: Clinical Trials Registry of India (CTRI/2025/06/088290).

]]> Development and Internal Validation of a Nurse-Led Sepsis Risk Score Using AI-Enabled Remote Patient Monitoring Data in Adult Febrile Neutropenia: A Nested Case–Control Study Aswathy Asokan Ajee Kurunjippadath Lakshmanan Sachin Suresh Jadhav Nancy Dias Premjith Bhavukam Renjitha Bhaskaran Kaippaplakal Thamikkutty Moly doi: 10.3390/diagnostics16223714 Diagnostics 2026-11-10 Diagnostics 2026-11-10 16 22 Article 3714 10.3390/diagnostics16223714 https://www.mdpi.com/2075-4418/16/22/3714 Diagnostics, Vol. 16, Pages 3713: Lightweight Calibration-Based Blood Pressure Tracking from Photoplethysmography Features for Smart Devices: Accuracy, Model Size and Recalibration Interval https://www.mdpi.com/2075-4418/16/22/3713 Background/Objectives: Smart devices estimate blood pressure (BP) from photoplethysmography (PPG), but models trained on other people generalize poorly, and device constraints limit model size. This study compared calibration strategies and model sizes for PPG-based BP estimation. Methods: We used 65 hand-crafted PPG features with MIMIC-BP (1295 training and 229 subject-disjoint test subjects, ten repeats) and 17 external VitalDB surgical cases. We compared calibration-free regressors, calibration with one to five cuffs, recalibration policies and calibration models of decreasing size. Results: Without calibration, six regressors reached a systolic BP (SBP) mean absolute error (MAE) of 13.0–13.3 mmHg on unseen subjects, close to a constant predictor (14.2 mmHg). A delta model that predicts the change from the cuff reading reduced the SBP MAE to 11.8 mmHg with one cuff and 10.8 mmHg with five, but followed only 30–50% of large changes. With five calibration readings, the model achieved a pooled area under the curve (AUC) of 0.94 for new-onset SBP ≥160 mmHg on MIMIC-BP, but sensitivity was zero at an estimated-SBP threshold of 160 mmHg. Accuracy was governed by the recalibration interval: recalibration nominally every 15 min gave 10.3 mmHg on VitalDB, and event-triggered cuffs were not better than periodic ones. A 47 KB tree model lost 0.2 mmHg against a 1.5 MB reference. Conclusions: For these data, calibration was required, the recalibration interval mattered more than model complexity, and a compact tree model was sufficient; on-device use requires further validation. Accuracy remained poor at blood-pressure extremes, and external validation in only 17 VitalDB cases remains preliminary. 2026-11-10 Diagnostics, Vol. 16, Pages 3713: Lightweight Calibration-Based Blood Pressure Tracking from Photoplethysmography Features for Smart Devices: Accuracy, Model Size and Recalibration Interval

Diagnostics doi: 10.3390/diagnostics16223713

Authors: Soojeong Lee Mugahed A. Al-antari Gangseong Lee

Background/Objectives: Smart devices estimate blood pressure (BP) from photoplethysmography (PPG), but models trained on other people generalize poorly, and device constraints limit model size. This study compared calibration strategies and model sizes for PPG-based BP estimation. Methods: We used 65 hand-crafted PPG features with MIMIC-BP (1295 training and 229 subject-disjoint test subjects, ten repeats) and 17 external VitalDB surgical cases. We compared calibration-free regressors, calibration with one to five cuffs, recalibration policies and calibration models of decreasing size. Results: Without calibration, six regressors reached a systolic BP (SBP) mean absolute error (MAE) of 13.0–13.3 mmHg on unseen subjects, close to a constant predictor (14.2 mmHg). A delta model that predicts the change from the cuff reading reduced the SBP MAE to 11.8 mmHg with one cuff and 10.8 mmHg with five, but followed only 30–50% of large changes. With five calibration readings, the model achieved a pooled area under the curve (AUC) of 0.94 for new-onset SBP ≥160 mmHg on MIMIC-BP, but sensitivity was zero at an estimated-SBP threshold of 160 mmHg. Accuracy was governed by the recalibration interval: recalibration nominally every 15 min gave 10.3 mmHg on VitalDB, and event-triggered cuffs were not better than periodic ones. A 47 KB tree model lost 0.2 mmHg against a 1.5 MB reference. Conclusions: For these data, calibration was required, the recalibration interval mattered more than model complexity, and a compact tree model was sufficient; on-device use requires further validation. Accuracy remained poor at blood-pressure extremes, and external validation in only 17 VitalDB cases remains preliminary.

]]> Lightweight Calibration-Based Blood Pressure Tracking from Photoplethysmography Features for Smart Devices: Accuracy, Model Size and Recalibration Interval Soojeong Lee Mugahed A. Al-antari Gangseong Lee doi: 10.3390/diagnostics16223713 Diagnostics 2026-11-10 Diagnostics 2026-11-10 16 22 Article 3713 10.3390/diagnostics16223713 https://www.mdpi.com/2075-4418/16/22/3713 Diagnostics, Vol. 16, Pages 3712: Gut Microbiota-Derived Biomarkers for the Non-Invasive Detection of Colorectal Cancer and Adenoma: A Systematic Review https://www.mdpi.com/2075-4418/16/22/3712 Background/Objectives: Gut microbiota dysbiosis is increasingly implicated in colorectal carcinogenesis, and microbial signatures are emerging as non-invasive diagnostic tools. This systematic review synthesised human studies that evaluated gut microbiota composition, microbiota-derived metabolites and microbial biomarkers for the detection of colorectal cancer (CRC) and colorectal adenoma. Methods: Following the PRISMA 2020 statement, PubMed/MEDLINE, Scopus and the Cochrane Library were searched for studies published between 2015 and 2025, supplemented by Google Scholar and reference-list screening. Human observational and interventional studies reporting microbiota-based diagnostic or associative endpoints were eligible. Data were synthesised narratively, and risk of bias was appraised with QUADAS-2; the protocol was not prospectively registered. Results: Ten studies (5318 participants; nine from East Asia, one from Europe) were included. Four used targeted quantitative PCR, three 16S rRNA sequencing and three shotgun metagenomics, all three combined with metabolomics. Fusobacterium nucleatum and Parvimonas micra were the taxa most frequently enriched in neoplasia (five studies each), together with Peptostreptococcus species, whereas butyrate-producing commensals (Faecalibacterium prausnitzii, Roseburia spp.) were depleted. Multi-omics panels achieved the highest discrimination for CRC (area under the curve [AUC] 0.92–0.994), while performance for adenoma was lower (AUC 0.64–0.91). Adding bacterial markers to the faecal immunochemical test (FIT) increased sensitivity for CRC and advanced adenoma at the cost of specificity. Most studies had a high or unclear risk of bias in the patient-selection and index-test domains, and only two evaluated a screening or mixed symptomatic population. No study reported microbial markers separately for the right colon, left colon and rectum, or for early-onset (<50 years) CRC, and age was often unbalanced between cases and controls. Conclusions: Microbiota-derived biomarkers show reproducible associations with colorectal neoplasia and promising diagnostic accuracy, particularly as adjuncts to FIT, but the evidence derives mainly from small, hospital-based case–control studies in East Asian populations, and accuracy for adenomas remains limited. Site-specific and early-onset data are lacking. Standardised, prospective, multi-ethnic validation studies are required before clinical implementation. 2026-11-10 Diagnostics, Vol. 16, Pages 3712: Gut Microbiota-Derived Biomarkers for the Non-Invasive Detection of Colorectal Cancer and Adenoma: A Systematic Review

Diagnostics doi: 10.3390/diagnostics16223712

Authors: Michelle Zsoldos Răzvan Alexandru Ciocan Claudia Diana Gherman Robeer Ghantus Horea Bocșe Florin Vasile Zaharie Nadim Al Hajjar Andra Ciocan

Background/Objectives: Gut microbiota dysbiosis is increasingly implicated in colorectal carcinogenesis, and microbial signatures are emerging as non-invasive diagnostic tools. This systematic review synthesised human studies that evaluated gut microbiota composition, microbiota-derived metabolites and microbial biomarkers for the detection of colorectal cancer (CRC) and colorectal adenoma. Methods: Following the PRISMA 2020 statement, PubMed/MEDLINE, Scopus and the Cochrane Library were searched for studies published between 2015 and 2025, supplemented by Google Scholar and reference-list screening. Human observational and interventional studies reporting microbiota-based diagnostic or associative endpoints were eligible. Data were synthesised narratively, and risk of bias was appraised with QUADAS-2; the protocol was not prospectively registered. Results: Ten studies (5318 participants; nine from East Asia, one from Europe) were included. Four used targeted quantitative PCR, three 16S rRNA sequencing and three shotgun metagenomics, all three combined with metabolomics. Fusobacterium nucleatum and Parvimonas micra were the taxa most frequently enriched in neoplasia (five studies each), together with Peptostreptococcus species, whereas butyrate-producing commensals (Faecalibacterium prausnitzii, Roseburia spp.) were depleted. Multi-omics panels achieved the highest discrimination for CRC (area under the curve [AUC] 0.92–0.994), while performance for adenoma was lower (AUC 0.64–0.91). Adding bacterial markers to the faecal immunochemical test (FIT) increased sensitivity for CRC and advanced adenoma at the cost of specificity. Most studies had a high or unclear risk of bias in the patient-selection and index-test domains, and only two evaluated a screening or mixed symptomatic population. No study reported microbial markers separately for the right colon, left colon and rectum, or for early-onset (<50 years) CRC, and age was often unbalanced between cases and controls. Conclusions: Microbiota-derived biomarkers show reproducible associations with colorectal neoplasia and promising diagnostic accuracy, particularly as adjuncts to FIT, but the evidence derives mainly from small, hospital-based case–control studies in East Asian populations, and accuracy for adenomas remains limited. Site-specific and early-onset data are lacking. Standardised, prospective, multi-ethnic validation studies are required before clinical implementation.

]]> Gut Microbiota-Derived Biomarkers for the Non-Invasive Detection of Colorectal Cancer and Adenoma: A Systematic Review Michelle Zsoldos Răzvan Alexandru Ciocan Claudia Diana Gherman Robeer Ghantus Horea Bocșe Florin Vasile Zaharie Nadim Al Hajjar Andra Ciocan doi: 10.3390/diagnostics16223712 Diagnostics 2026-11-10 Diagnostics 2026-11-10 16 22 Systematic Review 3712 10.3390/diagnostics16223712 https://www.mdpi.com/2075-4418/16/22/3712 Diagnostics, Vol. 16, Pages 3711: Cytology of HPV-Independent Cervical Carcinomas: Morphologic Spectrum, Clinical Correlates, and Ancillary Testing https://www.mdpi.com/2075-4418/16/22/3711 Cervical cancer is one of the most common cancers that can be diagnosed by cytologic features. While the past focus was mostly on human papillomavirus (HPV)-associated cervical carcinomas, the studies on HPV-independent cervical carcinomas have become more extensive with the advancement in ancillary tests, including molecular tests. The development of digital pathology also provides additional opportunities for more accurate cytologic diagnosis. We would like to summarise the current knowledge on the epidemiology, cytomorphology, and ancillary studies for different types of HPV-independent cervical carcinomas, and explore the use of digital pathology in the diagnosis of HPV-independent cervical carcinomas. Case reports, case series, and research articles are identified on PubMed using keywords “HPV-independent”, “cervical carcinomas”, “digital pathology”, and the specific names of subtypes of HPV-independent cervical carcinomas. The studies are selected based on their relevance to cytology, with an emphasis on new updates of ancillary tests. HPV-independent cervical carcinomas are classified based on the histological features, with distinct cytomorphological, immunocytochemical, and molecular features for each subtype. The prognosis is generally worse than HPV-associated cervical carcinomas. Accurate diagnosis is limited by a small number of cases and limited exposure among cytotechnicians and cytopathologists. The use of digital pathology can potentially improve diagnostic accuracy, while more studies are required before the adoption of digital pathology for the diagnosis of HPV-independent cervical carcinomas. Recognition of suspicious clinical features, liberal use of immunocytochemistry, and molecular testing are essential to accurate cytologic diagnosis of HPV-independent cervical carcinomas. 2026-11-10 Diagnostics, Vol. 16, Pages 3711: Cytology of HPV-Independent Cervical Carcinomas: Morphologic Spectrum, Clinical Correlates, and Ancillary Testing

Diagnostics doi: 10.3390/diagnostics16223711

Authors: Samuel O. H. Ching Joshua J. X. Li

Cervical cancer is one of the most common cancers that can be diagnosed by cytologic features. While the past focus was mostly on human papillomavirus (HPV)-associated cervical carcinomas, the studies on HPV-independent cervical carcinomas have become more extensive with the advancement in ancillary tests, including molecular tests. The development of digital pathology also provides additional opportunities for more accurate cytologic diagnosis. We would like to summarise the current knowledge on the epidemiology, cytomorphology, and ancillary studies for different types of HPV-independent cervical carcinomas, and explore the use of digital pathology in the diagnosis of HPV-independent cervical carcinomas. Case reports, case series, and research articles are identified on PubMed using keywords “HPV-independent”, “cervical carcinomas”, “digital pathology”, and the specific names of subtypes of HPV-independent cervical carcinomas. The studies are selected based on their relevance to cytology, with an emphasis on new updates of ancillary tests. HPV-independent cervical carcinomas are classified based on the histological features, with distinct cytomorphological, immunocytochemical, and molecular features for each subtype. The prognosis is generally worse than HPV-associated cervical carcinomas. Accurate diagnosis is limited by a small number of cases and limited exposure among cytotechnicians and cytopathologists. The use of digital pathology can potentially improve diagnostic accuracy, while more studies are required before the adoption of digital pathology for the diagnosis of HPV-independent cervical carcinomas. Recognition of suspicious clinical features, liberal use of immunocytochemistry, and molecular testing are essential to accurate cytologic diagnosis of HPV-independent cervical carcinomas.

]]> Cytology of HPV-Independent Cervical Carcinomas: Morphologic Spectrum, Clinical Correlates, and Ancillary Testing Samuel O. H. Ching Joshua J. X. Li doi: 10.3390/diagnostics16223711 Diagnostics 2026-11-10 Diagnostics 2026-11-10 16 22 Review 3711 10.3390/diagnostics16223711 https://www.mdpi.com/2075-4418/16/22/3711 Diagnostics, Vol. 16, Pages 3710: Intravascular Optical Coherence Tomography for Neuroendovascular Intervention: Applications, Devices, and Future Directions https://www.mdpi.com/2075-4418/16/22/3710 Background/Objectives: Intravascular optical coherence tomography (OCT) is a near-infrared light-based imaging modality with an axial resolution approaching 10 µm, roughly tenfold finer than intravascular ultrasound. Although OCT is established in coronary practice, its use in the cerebral circulation has been limited by catheter crossing profile, vessel tortuosity, and the need to clear blood from the vascular lumen during acquisition. In this narrative review, we summarize the physical principles of OCT, its plaque-characterization criteria and their histologic validation, the coronary evidence base, the imaging hardware available for intracranial use, and the reported clinical applications across intracranial atherosclerotic disease, intracranial aneurysms treated with flow diverters, carotid disease and carotid webs, arterial dissection, and venous and thromboembolic disease. We also discuss the technical barriers that limit routine neuroendovascular use. Methods: MEDLINE and PubMed were searched from inception through 1 September 2026 for English-language reports of intravascular OCT in human or animal cervical and intracranial vessels; study selection was not systematic. Results: The evidence base is composed largely of preclinical models, small human feasibility series, and case reports; no randomized or large-scale clinical outcome data exist. OCT has been feasible in selected cerebrovascular series, but the pooled evidence comes largely from extracranial carotid studies and does not establish its performance in intracranial vessels. Dedicated neurovascular probes have recently entered clinical study. In the coronary circulation, randomized evidence supports intravascular imaging-guided stent implantation and OCT-defined plaque features are associated with events; corresponding benefits have not been established intracranially. Conclusions: Intravascular OCT resolves the cerebral arterial wall and endoluminal devices in detail, but its safety and clinical benefit in neuroendovascular practice require further study. Prospective studies are needed to determine whether OCT findings change management and improve patient outcomes. 2026-11-10 Diagnostics, Vol. 16, Pages 3710: Intravascular Optical Coherence Tomography for Neuroendovascular Intervention: Applications, Devices, and Future Directions

Diagnostics doi: 10.3390/diagnostics16223710

Authors: Huanwen Chen Marco Colasurdo Ajay Malhotra Mohamed A. M. Labib Dhairya A. Lakhani Dheeraj Gandhi

Background/Objectives: Intravascular optical coherence tomography (OCT) is a near-infrared light-based imaging modality with an axial resolution approaching 10 µm, roughly tenfold finer than intravascular ultrasound. Although OCT is established in coronary practice, its use in the cerebral circulation has been limited by catheter crossing profile, vessel tortuosity, and the need to clear blood from the vascular lumen during acquisition. In this narrative review, we summarize the physical principles of OCT, its plaque-characterization criteria and their histologic validation, the coronary evidence base, the imaging hardware available for intracranial use, and the reported clinical applications across intracranial atherosclerotic disease, intracranial aneurysms treated with flow diverters, carotid disease and carotid webs, arterial dissection, and venous and thromboembolic disease. We also discuss the technical barriers that limit routine neuroendovascular use. Methods: MEDLINE and PubMed were searched from inception through 1 September 2026 for English-language reports of intravascular OCT in human or animal cervical and intracranial vessels; study selection was not systematic. Results: The evidence base is composed largely of preclinical models, small human feasibility series, and case reports; no randomized or large-scale clinical outcome data exist. OCT has been feasible in selected cerebrovascular series, but the pooled evidence comes largely from extracranial carotid studies and does not establish its performance in intracranial vessels. Dedicated neurovascular probes have recently entered clinical study. In the coronary circulation, randomized evidence supports intravascular imaging-guided stent implantation and OCT-defined plaque features are associated with events; corresponding benefits have not been established intracranially. Conclusions: Intravascular OCT resolves the cerebral arterial wall and endoluminal devices in detail, but its safety and clinical benefit in neuroendovascular practice require further study. Prospective studies are needed to determine whether OCT findings change management and improve patient outcomes.

]]> Intravascular Optical Coherence Tomography for Neuroendovascular Intervention: Applications, Devices, and Future Directions Huanwen Chen Marco Colasurdo Ajay Malhotra Mohamed A. M. Labib Dhairya A. Lakhani Dheeraj Gandhi doi: 10.3390/diagnostics16223710 Diagnostics 2026-11-10 Diagnostics 2026-11-10 16 22 Review 3710 10.3390/diagnostics16223710 https://www.mdpi.com/2075-4418/16/22/3710 Diagnostics, Vol. 16, Pages 3709: Convolutional Neural Network-Based Deep Learning Models for Diagnosis of Oral Squamous Cell Carcinoma and Oral Potentially Malignant Disorders: A Scoping Review https://www.mdpi.com/2075-4418/16/22/3709 Background/Objectives: Oral squamous cell carcinoma (OSCC) represents the most common oral malignancy, accounting for over 90% of cases, with a five-year survival rate of approximately 50%. Oral potentially malignant disorders (OPMDs) carry an inherent risk of malignant transformation to OSCC, yet early and accurate diagnosis of both conditions remains challenging in clinical practice, owing to lesion heterogeneity and inter-observer variability in histopathological interpretation. While existing reviews have addressed artificial intelligence (AI) models’ diagnostic performance in oral oncology, these have typically combined varied model types and have not restricted inclusion to studies based on a held-out test set. This scoping review maps convolutional neural network (CNN)-based models applied with explicit diagnostic intent primarily to OSCC, with exploratory coverage of OPMDs, across histopathological and clinical photographic imaging, limited to studies reporting performance on held-out test data separate from model development. Methods: Following PRISMA-ScR guidelines, a systematic search was conducted in August 2025 across Scopus, PubMed, and the Cochrane Library. Studies were included if they applied CNN-based models with explicit diagnostic intent for OPMDs and/or OSCC using histopathological or clinical photographic images and reported quantitative diagnostic performance on a held-out test set. Extracted data included model architecture, imaging modality, dataset characteristics, and performance metrics comprising accuracy, sensitivity, specificity, precision, recall, F1-score, and AUC (area under the receiver operating characteristic curve). Results: Thirty studies published between 2020 and 2025 were included. CNN-based models reported generally favorable diagnostic performance, particularly with histopathological images, with accuracy frequently exceeding 90%. Models utilizing clinical photographic images demonstrated greater variability, with accuracy ranging from approximately 76% to 97.5%, in the seven of 13 studies that reported it. Across both modalities, binary classification tasks generally outperformed multi-class differentiation. Inconsistent metric reporting, reliance on small single-institution datasets, and near-absent reporting of external validation were observed as recurring methodological limitations. Conclusions: CNN-based models reported high diagnostic performance for OSCC, particularly in histopathological binary classification settings, although evidence for OPMD subtypes remains limited. However, translating this into clinical practice will require investment in large shared data repositories, standardized reporting of performance metrics, rigorous benchmarking against human experts, and external and prospective clinical validation. 2026-11-10 Diagnostics, Vol. 16, Pages 3709: Convolutional Neural Network-Based Deep Learning Models for Diagnosis of Oral Squamous Cell Carcinoma and Oral Potentially Malignant Disorders: A Scoping Review

Diagnostics doi: 10.3390/diagnostics16223709

Authors: Pooja Gadhvi Annette Si-Ki Ng Priyanka Gudsoorkar Jessica Klabak Sujay A. J. Mehta

Background/Objectives: Oral squamous cell carcinoma (OSCC) represents the most common oral malignancy, accounting for over 90% of cases, with a five-year survival rate of approximately 50%. Oral potentially malignant disorders (OPMDs) carry an inherent risk of malignant transformation to OSCC, yet early and accurate diagnosis of both conditions remains challenging in clinical practice, owing to lesion heterogeneity and inter-observer variability in histopathological interpretation. While existing reviews have addressed artificial intelligence (AI) models’ diagnostic performance in oral oncology, these have typically combined varied model types and have not restricted inclusion to studies based on a held-out test set. This scoping review maps convolutional neural network (CNN)-based models applied with explicit diagnostic intent primarily to OSCC, with exploratory coverage of OPMDs, across histopathological and clinical photographic imaging, limited to studies reporting performance on held-out test data separate from model development. Methods: Following PRISMA-ScR guidelines, a systematic search was conducted in August 2025 across Scopus, PubMed, and the Cochrane Library. Studies were included if they applied CNN-based models with explicit diagnostic intent for OPMDs and/or OSCC using histopathological or clinical photographic images and reported quantitative diagnostic performance on a held-out test set. Extracted data included model architecture, imaging modality, dataset characteristics, and performance metrics comprising accuracy, sensitivity, specificity, precision, recall, F1-score, and AUC (area under the receiver operating characteristic curve). Results: Thirty studies published between 2020 and 2025 were included. CNN-based models reported generally favorable diagnostic performance, particularly with histopathological images, with accuracy frequently exceeding 90%. Models utilizing clinical photographic images demonstrated greater variability, with accuracy ranging from approximately 76% to 97.5%, in the seven of 13 studies that reported it. Across both modalities, binary classification tasks generally outperformed multi-class differentiation. Inconsistent metric reporting, reliance on small single-institution datasets, and near-absent reporting of external validation were observed as recurring methodological limitations. Conclusions: CNN-based models reported high diagnostic performance for OSCC, particularly in histopathological binary classification settings, although evidence for OPMD subtypes remains limited. However, translating this into clinical practice will require investment in large shared data repositories, standardized reporting of performance metrics, rigorous benchmarking against human experts, and external and prospective clinical validation.

]]> Convolutional Neural Network-Based Deep Learning Models for Diagnosis of Oral Squamous Cell Carcinoma and Oral Potentially Malignant Disorders: A Scoping Review Pooja Gadhvi Annette Si-Ki Ng Priyanka Gudsoorkar Jessica Klabak Sujay A. J. Mehta doi: 10.3390/diagnostics16223709 Diagnostics 2026-11-10 Diagnostics 2026-11-10 16 22 Review 3709 10.3390/diagnostics16223709 https://www.mdpi.com/2075-4418/16/22/3709 Diagnostics, Vol. 16, Pages 3708: Linear IgA Disease with Oral and Laryngeal Mucosal Involvement in an Elderly Denture Wearer: A Case Report and Literature Review https://www.mdpi.com/2075-4418/16/22/3708 Background and Clinical Significance: Linear IgA disease (LAD) is a rare autoimmune subepithelial blistering disorder characterized by linear IgA deposition along the basement membrane zone (BMZ). Oral and laryngeal involvement is exceptionally rare and can mimic other autoimmune blistering diseases. We report such a case and review previously published cases. Case Presentation: An 85-year-old denture-wearing woman with ulcerative colitis (UC) and chronic oral erosions since 2019 underwent clinical, histopathological, immunofluorescence, and serological evaluations, as well as laryngoscopy. Medication exposure and denture-related injury were reviewed as possible triggers. Previously diagnosed as oral lichen planus (OLP) and bullous pemphigoid (BP), the lesions showed strong linear IgA (3+) and moderate C3 (2+) deposition along the BMZ on direct immunofluorescence (DIF); serological tests for pemphigoid and pemphigus antigens were negative. Laryngoscopy revealed edema, fibrinous deposits, and early scarring. After drug-related and denture-related causes were considered unlikely, a clinicopathologic diagnosis of mucosal-predominant LAD was made; because salt-split skin indirect immunofluorescence (IIF) and antigen-specific testing were unavailable, IgA-predominant mucous membrane pemphigoid (MMP) could not be completely excluded. Dapsone produced marked improvement but was discontinued because of severe hemolytic anemia; laryngeal edema later caused respiratory insufficiency. A structured literature review of English-language reports published since 2016 identified three previously reported cases of LAD limited to the oral mucosa. No prior case with simultaneous oral and laryngeal involvement without skin disease was identified, although one report described LAD confined to the hypopharyngeal and laryngeal mucosa. Conclusions: DIF is essential for diagnosis, LAD must be distinguished from IgA-predominant MMP, and laryngeal involvement requires early recognition. Because linear IgA deposition in adults may be reactive, drug-induced and denture-related injury should be excluded, and dapsone toxicity monitored. 2026-11-10 Diagnostics, Vol. 16, Pages 3708: Linear IgA Disease with Oral and Laryngeal Mucosal Involvement in an Elderly Denture Wearer: A Case Report and Literature Review

Diagnostics doi: 10.3390/diagnostics16223708

Authors: Ana Glavina Tina Gogić Salapić Braco Bošković Nikolina Smajkan Merica Glavina Durdov Antonija Tadin Daniela Šupe-Domić

Background and Clinical Significance: Linear IgA disease (LAD) is a rare autoimmune subepithelial blistering disorder characterized by linear IgA deposition along the basement membrane zone (BMZ). Oral and laryngeal involvement is exceptionally rare and can mimic other autoimmune blistering diseases. We report such a case and review previously published cases. Case Presentation: An 85-year-old denture-wearing woman with ulcerative colitis (UC) and chronic oral erosions since 2019 underwent clinical, histopathological, immunofluorescence, and serological evaluations, as well as laryngoscopy. Medication exposure and denture-related injury were reviewed as possible triggers. Previously diagnosed as oral lichen planus (OLP) and bullous pemphigoid (BP), the lesions showed strong linear IgA (3+) and moderate C3 (2+) deposition along the BMZ on direct immunofluorescence (DIF); serological tests for pemphigoid and pemphigus antigens were negative. Laryngoscopy revealed edema, fibrinous deposits, and early scarring. After drug-related and denture-related causes were considered unlikely, a clinicopathologic diagnosis of mucosal-predominant LAD was made; because salt-split skin indirect immunofluorescence (IIF) and antigen-specific testing were unavailable, IgA-predominant mucous membrane pemphigoid (MMP) could not be completely excluded. Dapsone produced marked improvement but was discontinued because of severe hemolytic anemia; laryngeal edema later caused respiratory insufficiency. A structured literature review of English-language reports published since 2016 identified three previously reported cases of LAD limited to the oral mucosa. No prior case with simultaneous oral and laryngeal involvement without skin disease was identified, although one report described LAD confined to the hypopharyngeal and laryngeal mucosa. Conclusions: DIF is essential for diagnosis, LAD must be distinguished from IgA-predominant MMP, and laryngeal involvement requires early recognition. Because linear IgA deposition in adults may be reactive, drug-induced and denture-related injury should be excluded, and dapsone toxicity monitored.

]]> Linear IgA Disease with Oral and Laryngeal Mucosal Involvement in an Elderly Denture Wearer: A Case Report and Literature Review Ana Glavina Tina Gogić Salapić Braco Bošković Nikolina Smajkan Merica Glavina Durdov Antonija Tadin Daniela Šupe-Domić doi: 10.3390/diagnostics16223708 Diagnostics 2026-11-10 Diagnostics 2026-11-10 16 22 Case Report 3708 10.3390/diagnostics16223708 https://www.mdpi.com/2075-4418/16/22/3708 Diagnostics, Vol. 16, Pages 3707: First-Line CDK4/6 Inhibitor Outcomes in HER2-Low Versus HER2-Zero Hormone-Receptor-Positive Metastatic Breast Cancer: A Single-Centre Real-World Cohort Study https://www.mdpi.com/2075-4418/16/22/3707 Background: A CDK4/6 inhibitor plus endocrine therapy is the standard first-line treatment for hormone receptor (HR)-positive, HER2-negative metastatic breast cancer. Post hoc analyses of randomised trials have raised the possibility that HER2-low status influences CDK4/6 inhibitor benefit, whereas real-world data are limited. We compared outcomes between patients with HER2-low and HER2-zero disease treated with first-line CDK4/6-inhibitor-based therapy in a real-world cohort. Methods: In this single-centre retrospective cohort study, we identified 137 patients with HR-positive, HER2-negative metastatic breast cancer who received first-line ribociclib or palbociclib plus endocrine therapy between January 2017 and December 2024. HER2-zero was defined as an immunohistochemistry (IHC) score of 0 and HER2-low as IHC 1+ or 2+ without gene amplification. Objective response, progression-free survival (PFS), overall survival (OS), and neutropenia were compared; Cox models were adjusted for recognised prognostic factors. Results: Of 137 patients, 98 (71.5%) had HER2-zero and 39 (28.5%) HER2-low disease; median follow-up was 29.5 months. Objective response rates were 63.9% versus 56.4% (p = 0.44). Median PFS was 31.4 versus 28.5 months (63 events in 134 evaluable patients; log-rank p = 0.70), and median OS was 69.7 months versus not reached (34 deaths in 127 evaluable patients; p = 0.95). Adjusted hazard ratios for HER2-low versus HER2-zero were 1.01 (95% CI 0.57–1.80) for PFS and 1.04 (95% CI 0.49–2.19) for OS. Any-grade and grade ≥3 neutropenia and dose reductions did not differ. Results were consistent across IHC categories (0, 1+, 2+) and in propensity-score-weighted and misclassification bias analyses, all with wide confidence intervals. Conclusions: In this single-centre real-world cohort, response, survival and tolerability of first-line CDK4/6-inhibitor-based therapy did not differ significantly between HER2-low and HER2-zero disease. However, with only 39 HER2-low patients the study was underpowered: it had 80% power to detect only a PFS hazard ratio of approximately 2.2, so clinically relevant differences cannot be excluded. Because all patients received a CDK4/6 inhibitor, these prognostic data cannot show whether HER2-low status modifies the CDK4/6 inhibitor benefit. The findings are hypothesis-generating and require confirmation in larger, adequately powered studies. 2026-11-10 Diagnostics, Vol. 16, Pages 3707: First-Line CDK4/6 Inhibitor Outcomes in HER2-Low Versus HER2-Zero Hormone-Receptor-Positive Metastatic Breast Cancer: A Single-Centre Real-World Cohort Study

Diagnostics doi: 10.3390/diagnostics16223707

Authors: Mehmet Acun Mehmet Mutlu Çatlı Arif Hakan Önder

Background: A CDK4/6 inhibitor plus endocrine therapy is the standard first-line treatment for hormone receptor (HR)-positive, HER2-negative metastatic breast cancer. Post hoc analyses of randomised trials have raised the possibility that HER2-low status influences CDK4/6 inhibitor benefit, whereas real-world data are limited. We compared outcomes between patients with HER2-low and HER2-zero disease treated with first-line CDK4/6-inhibitor-based therapy in a real-world cohort. Methods: In this single-centre retrospective cohort study, we identified 137 patients with HR-positive, HER2-negative metastatic breast cancer who received first-line ribociclib or palbociclib plus endocrine therapy between January 2017 and December 2024. HER2-zero was defined as an immunohistochemistry (IHC) score of 0 and HER2-low as IHC 1+ or 2+ without gene amplification. Objective response, progression-free survival (PFS), overall survival (OS), and neutropenia were compared; Cox models were adjusted for recognised prognostic factors. Results: Of 137 patients, 98 (71.5%) had HER2-zero and 39 (28.5%) HER2-low disease; median follow-up was 29.5 months. Objective response rates were 63.9% versus 56.4% (p = 0.44). Median PFS was 31.4 versus 28.5 months (63 events in 134 evaluable patients; log-rank p = 0.70), and median OS was 69.7 months versus not reached (34 deaths in 127 evaluable patients; p = 0.95). Adjusted hazard ratios for HER2-low versus HER2-zero were 1.01 (95% CI 0.57–1.80) for PFS and 1.04 (95% CI 0.49–2.19) for OS. Any-grade and grade ≥3 neutropenia and dose reductions did not differ. Results were consistent across IHC categories (0, 1+, 2+) and in propensity-score-weighted and misclassification bias analyses, all with wide confidence intervals. Conclusions: In this single-centre real-world cohort, response, survival and tolerability of first-line CDK4/6-inhibitor-based therapy did not differ significantly between HER2-low and HER2-zero disease. However, with only 39 HER2-low patients the study was underpowered: it had 80% power to detect only a PFS hazard ratio of approximately 2.2, so clinically relevant differences cannot be excluded. Because all patients received a CDK4/6 inhibitor, these prognostic data cannot show whether HER2-low status modifies the CDK4/6 inhibitor benefit. The findings are hypothesis-generating and require confirmation in larger, adequately powered studies.

]]> First-Line CDK4/6 Inhibitor Outcomes in HER2-Low Versus HER2-Zero Hormone-Receptor-Positive Metastatic Breast Cancer: A Single-Centre Real-World Cohort Study Mehmet Acun Mehmet Mutlu Çatlı Arif Hakan Önder doi: 10.3390/diagnostics16223707 Diagnostics 2026-11-10 Diagnostics 2026-11-10 16 22 Article 3707 10.3390/diagnostics16223707 https://www.mdpi.com/2075-4418/16/22/3707 Diagnostics, Vol. 16, Pages 3706: Temporal Patterns of Serum Neuroprotectin D1 and Resolvin D1 After Motor and Nonmotor Epileptic Seizures: A Prospective Repeated-Measures Study https://www.mdpi.com/2075-4418/16/21/3706 Objective: Neuroinflammatory activation is well recognized in epilepsy, whereas the temporal behavior of specialized pro-resolving mediator (SPM) responses after seizures remains poorly defined. We evaluated changes in serum neuroprotectin D1 (NP-1) and resolvin D1 (RvD1) between the early postictal period and a seizure-free period of at least 1 month and compared both time points with healthy controls. Methods: This prospective controlled repeated-measures study included 48 adults with epilepsy and 50 healthy controls. Blood was obtained within 3 h after a seizure and again after at least 1 month of seizure freedom; controls provided one sample. Serum NP-1 and resolvin D1 (RvD1) were measured using commercial enzyme-linked immunosorbent assay (ELISA) kits. The prespecified primary analysis compared paired postictal and seizure-free measurements using the Wilcoxon signed-rank test. Patient-control comparisons were considered secondary/exploratory. Results: Median NP-1 increased from 50.01 ng/mL (IQR 3.58–98.62) postictally to 67.78 ng/mL (59.81–121.81) during the seizure-free period (Z = −5.333, p < 0.001, r = 0.770). RvD1 did not change significantly (326.67 [207.77–899.95] vs. 441.47 [223.67–710.81] pg/mL; p = 0.139, r = 0.215). Both mediators were lower than controls postictally (both p < 0.001). During seizure freedom, NP-1 and RvD1 remained lower than controls (p = 0.008 and p < 0.001, respectively). The absolute percentage difference from the control median was greater for RvD1 than for NP-1 during seizure freedom (60.74% vs. 42.84%; p = 0.001, r = 0.462). Conclusions: The pro-resolving response in epilepsy appears temporally heterogeneous. NP-1 showed substantial within-patient recovery, whereas Resolvin D1 remained persistently reduced. These findings are hypothesis-generating and support larger serial-sampling studies with targeted lipidomic validation rather than establishing either mediator as a diagnostic biomarker. 2026-11-09 Diagnostics, Vol. 16, Pages 3706: Temporal Patterns of Serum Neuroprotectin D1 and Resolvin D1 After Motor and Nonmotor Epileptic Seizures: A Prospective Repeated-Measures Study

Diagnostics doi: 10.3390/diagnostics16213706

Authors: Ahmet Sengul Irem Tasci Ayse Berilgen Gurgoze Sait Albayrak Selda Telo

Objective: Neuroinflammatory activation is well recognized in epilepsy, whereas the temporal behavior of specialized pro-resolving mediator (SPM) responses after seizures remains poorly defined. We evaluated changes in serum neuroprotectin D1 (NP-1) and resolvin D1 (RvD1) between the early postictal period and a seizure-free period of at least 1 month and compared both time points with healthy controls. Methods: This prospective controlled repeated-measures study included 48 adults with epilepsy and 50 healthy controls. Blood was obtained within 3 h after a seizure and again after at least 1 month of seizure freedom; controls provided one sample. Serum NP-1 and resolvin D1 (RvD1) were measured using commercial enzyme-linked immunosorbent assay (ELISA) kits. The prespecified primary analysis compared paired postictal and seizure-free measurements using the Wilcoxon signed-rank test. Patient-control comparisons were considered secondary/exploratory. Results: Median NP-1 increased from 50.01 ng/mL (IQR 3.58–98.62) postictally to 67.78 ng/mL (59.81–121.81) during the seizure-free period (Z = −5.333, p < 0.001, r = 0.770). RvD1 did not change significantly (326.67 [207.77–899.95] vs. 441.47 [223.67–710.81] pg/mL; p = 0.139, r = 0.215). Both mediators were lower than controls postictally (both p < 0.001). During seizure freedom, NP-1 and RvD1 remained lower than controls (p = 0.008 and p < 0.001, respectively). The absolute percentage difference from the control median was greater for RvD1 than for NP-1 during seizure freedom (60.74% vs. 42.84%; p = 0.001, r = 0.462). Conclusions: The pro-resolving response in epilepsy appears temporally heterogeneous. NP-1 showed substantial within-patient recovery, whereas Resolvin D1 remained persistently reduced. These findings are hypothesis-generating and support larger serial-sampling studies with targeted lipidomic validation rather than establishing either mediator as a diagnostic biomarker.

]]> Temporal Patterns of Serum Neuroprotectin D1 and Resolvin D1 After Motor and Nonmotor Epileptic Seizures: A Prospective Repeated-Measures Study Ahmet Sengul Irem Tasci Ayse Berilgen Gurgoze Sait Albayrak Selda Telo doi: 10.3390/diagnostics16213706 Diagnostics 2026-11-09 Diagnostics 2026-11-09 16 21 Article 3706 10.3390/diagnostics16213706 https://www.mdpi.com/2075-4418/16/21/3706 Diagnostics, Vol. 16, Pages 3704: Paradoxical Splenic Signal Loss on Chemical-Shift MRI in Acute Toxic Hepatitis After Occupational Petroleum Sludge Exposure: A Case Series https://www.mdpi.com/2075-4418/16/21/3704 Background: Acute toxic hepatitis after work-related exposure to petroleum products is rare. Its imaging features are not well known. Methods: Seven men aged 18–35 years cleaned the same petroleum storage tank for two days. Symptoms began about 5 days later. Ultrasound and CT were done at admission. Non-contrast 3 T MRI with in-phase and opposed-phase imaging was done about 10 days after exposure. The splenic signal intensity ratio (SIR, in-phase/opposed-phase) was compared with that of 15 age- and sex-matched healthy controls. Results: At admission, median ALT was 481 U/L, median AST 227 U/L, and median total bilirubin 6.1 mg/dL. The injury was hepatocellular by R ratio in the six patients with raised ALT. Periportal edema was seen in 6 of 7 patients. No patient had biliary obstruction or vascular thrombosis. Notably, all seven patients demonstrated paradoxical splenic signal loss on in-phase compared with opposed-phase MRI, with a median splenic signal intensity ratio (SIR) of 0.77 (IQR, 0.74–0.81; range, 0.70–0.87). Splenic SIR was lower in patients than in healthy controls (median 0.77 vs. 1.05; p < 0.001). All patients recovered with supportive care. Conclusions: In this single exposure cluster, the spleen lost signal on in-phase images. This pattern is usually linked to iron or other T2* effects. The finding is preliminary. It needs confirmation with iron measurement, hemolysis tests, and follow-up MRI. 2026-11-09 Diagnostics, Vol. 16, Pages 3704: Paradoxical Splenic Signal Loss on Chemical-Shift MRI in Acute Toxic Hepatitis After Occupational Petroleum Sludge Exposure: A Case Series

Diagnostics doi: 10.3390/diagnostics16213704

Authors: Bişar Akbaş Mustafa Oğuz Tuğcan Fatma Efe Nisanur Yardımcı Ferhat Can Pişkin Eylül Akbal Hasan Bilen Onan

Background: Acute toxic hepatitis after work-related exposure to petroleum products is rare. Its imaging features are not well known. Methods: Seven men aged 18–35 years cleaned the same petroleum storage tank for two days. Symptoms began about 5 days later. Ultrasound and CT were done at admission. Non-contrast 3 T MRI with in-phase and opposed-phase imaging was done about 10 days after exposure. The splenic signal intensity ratio (SIR, in-phase/opposed-phase) was compared with that of 15 age- and sex-matched healthy controls. Results: At admission, median ALT was 481 U/L, median AST 227 U/L, and median total bilirubin 6.1 mg/dL. The injury was hepatocellular by R ratio in the six patients with raised ALT. Periportal edema was seen in 6 of 7 patients. No patient had biliary obstruction or vascular thrombosis. Notably, all seven patients demonstrated paradoxical splenic signal loss on in-phase compared with opposed-phase MRI, with a median splenic signal intensity ratio (SIR) of 0.77 (IQR, 0.74–0.81; range, 0.70–0.87). Splenic SIR was lower in patients than in healthy controls (median 0.77 vs. 1.05; p < 0.001). All patients recovered with supportive care. Conclusions: In this single exposure cluster, the spleen lost signal on in-phase images. This pattern is usually linked to iron or other T2* effects. The finding is preliminary. It needs confirmation with iron measurement, hemolysis tests, and follow-up MRI.

]]> Paradoxical Splenic Signal Loss on Chemical-Shift MRI in Acute Toxic Hepatitis After Occupational Petroleum Sludge Exposure: A Case Series Bişar Akbaş Mustafa Oğuz Tuğcan Fatma Efe Nisanur Yardımcı Ferhat Can Pişkin Eylül Akbal Hasan Bilen Onan doi: 10.3390/diagnostics16213704 Diagnostics 2026-11-09 Diagnostics 2026-11-09 16 21 Article 3704 10.3390/diagnostics16213704 https://www.mdpi.com/2075-4418/16/21/3704 Diagnostics, Vol. 16, Pages 3705: Cross-Phenotype Genomics Reveals Heterogeneous Genetic Susceptibility Architecture Relevant to Menopause https://www.mdpi.com/2075-4418/16/21/3705 Background: Menopause is accompanied by substantial interindividual variation in hormonal, metabolic, cardiovascular, skeletal, and thrombotic phenotypes. Although the genetics of reproductive ageing and individual menopause-associated traits are increasingly characterised, the cross-phenotype architecture of individual menopause-relevant germline variants remains less well defined. Methods: We performed a variant-centred genomic analysis of 31 prespecified menopause-relevant germline variants. Cross-trait evidence comprised 766 variant-trait records across 52 phenotypes and was integrated with a targeted Pan-UK Biobank phenome-wide association study (PheWAS; 1462 tests across 57 endpoints), clinically relevant outcome analyses, linkage disequilibrium assessment, FinnGen R12 venous thromboembolism (VTE) associations, regional fine-mapping, and molecular annotation. Association strength, between-study heterogeneity, phenotypic breadth and sharing, and locus resolution were evaluated as distinct evidence dimensions. Results: In total, 25 of 31 variants showed at least one cross-trait association at p < 1 × 10−5 and 21 reached genome-wide significance. Phenotypic breadth varied markedly, from restricted profiles to 16 associated phenotypes, and strong associations frequently coexisted with substantial between-study heterogeneity. In Pan-UK Biobank, 222 associations involving 25 variants met false-discovery-rate correction, spanning hormonal, reproductive, cardiometabolic, skeletal, nutritional, hepatic, and neurological phenotypes. Cross-phenotype reconstruction identified recurrent connectivity through sex hormone-binding globulin, testosterone, adiposity, lipid, and skeletal traits, while linkage disequilibrium analyses distinguished phenotypic sharing from genetic redundancy. Clinically, F5 rs6025 and F2 rs1799963 showed strong VTE associations in FinnGen (OR 2.387 and 1.921, respectively), but markedly different locus resolution: rs6025 had posterior inclusion probability (PIP) 0.979 and constituted a single-variant 95% credible set, whereas rs1799963 had PIP 0.596 within a four-variant credible set. Conclusions: Menopause-relevant germline variation exhibits heterogeneous cross-phenotype architectures in which association strength, phenotypic breadth, between-study consistency, genetic independence, and locus resolution are not interchangeable. This variant-centred framework provides a basis for evaluating inherited susceptibility relevant to menopause and hormone exposure, while prospective individual-level studies remain necessary before translation into risk prediction or treatment selection. 2026-11-09 Diagnostics, Vol. 16, Pages 3705: Cross-Phenotype Genomics Reveals Heterogeneous Genetic Susceptibility Architecture Relevant to Menopause

Diagnostics doi: 10.3390/diagnostics16213705

Authors: Gustavo Torres De Souza Laura Vila-Vecilla Valentina Russo Caroline Brandão Chiovatto Adil Yafou El Kayori

Background: Menopause is accompanied by substantial interindividual variation in hormonal, metabolic, cardiovascular, skeletal, and thrombotic phenotypes. Although the genetics of reproductive ageing and individual menopause-associated traits are increasingly characterised, the cross-phenotype architecture of individual menopause-relevant germline variants remains less well defined. Methods: We performed a variant-centred genomic analysis of 31 prespecified menopause-relevant germline variants. Cross-trait evidence comprised 766 variant-trait records across 52 phenotypes and was integrated with a targeted Pan-UK Biobank phenome-wide association study (PheWAS; 1462 tests across 57 endpoints), clinically relevant outcome analyses, linkage disequilibrium assessment, FinnGen R12 venous thromboembolism (VTE) associations, regional fine-mapping, and molecular annotation. Association strength, between-study heterogeneity, phenotypic breadth and sharing, and locus resolution were evaluated as distinct evidence dimensions. Results: In total, 25 of 31 variants showed at least one cross-trait association at p < 1 × 10−5 and 21 reached genome-wide significance. Phenotypic breadth varied markedly, from restricted profiles to 16 associated phenotypes, and strong associations frequently coexisted with substantial between-study heterogeneity. In Pan-UK Biobank, 222 associations involving 25 variants met false-discovery-rate correction, spanning hormonal, reproductive, cardiometabolic, skeletal, nutritional, hepatic, and neurological phenotypes. Cross-phenotype reconstruction identified recurrent connectivity through sex hormone-binding globulin, testosterone, adiposity, lipid, and skeletal traits, while linkage disequilibrium analyses distinguished phenotypic sharing from genetic redundancy. Clinically, F5 rs6025 and F2 rs1799963 showed strong VTE associations in FinnGen (OR 2.387 and 1.921, respectively), but markedly different locus resolution: rs6025 had posterior inclusion probability (PIP) 0.979 and constituted a single-variant 95% credible set, whereas rs1799963 had PIP 0.596 within a four-variant credible set. Conclusions: Menopause-relevant germline variation exhibits heterogeneous cross-phenotype architectures in which association strength, phenotypic breadth, between-study consistency, genetic independence, and locus resolution are not interchangeable. This variant-centred framework provides a basis for evaluating inherited susceptibility relevant to menopause and hormone exposure, while prospective individual-level studies remain necessary before translation into risk prediction or treatment selection.

]]> Cross-Phenotype Genomics Reveals Heterogeneous Genetic Susceptibility Architecture Relevant to Menopause Gustavo Torres De Souza Laura Vila-Vecilla Valentina Russo Caroline Brandão Chiovatto Adil Yafou El Kayori doi: 10.3390/diagnostics16213705 Diagnostics 2026-11-09 Diagnostics 2026-11-09 16 21 Article 3705 10.3390/diagnostics16213705 https://www.mdpi.com/2075-4418/16/21/3705 Diagnostics, Vol. 16, Pages 3703: Reproducibility Before Treatment Decision Rules: A Targeted Scoping Review of AI-Assisted Coronary Plaque Characterization https://www.mdpi.com/2075-4418/16/21/3703 Background/Objectives: Coronary computed tomography angiography (CCTA) can quantify plaque, whose burden predicts myocardial infarction better than stenosis severity. We reviewed evidence for artificial intelligence (AI)-assisted plaque characterization. Methods: This targeted scoping review (PRISMA-ScR) used a non-exhaustive search, mainly of MEDLINE/PubMed (July 2026, supplemented in September). AI title selection (135 of 1415 titles) and author assessment of 141 records yielded 121 included records under the revised criteria. An AI re-screen of 1280 unselected records (blind second pass on 175) found 110 further eligible records after charting; two AI passes screened 3634 confirmatory records (κ 0.93). The corresponding author accepted AI recommendations after reviewing written assessments, not blind (for the 335 confirmatory records, in one instruction). Of the 543 eligible records, 236 were charted (121 + 110 + 4 + 1; full text for 121 of the 236, abstract alone for 115) and 307 mapped from abstracts only (not fully charted). Results: In symptomatic or referred patients, AI-derived plaque burden was associated with major adverse cardiovascular events (a property of the measurement, not evidence that AI improves outcomes). In one comparison, AI modestly improved discrimination over manual quantification (AUC 0.82 vs. 0.78) without significant net reclassification improvement. No randomized trial of AI-based plaque analysis reporting clinical endpoints was identified in the sources searched and assessed; TRANSFORM (NCT06112418) is recruiting. Three small same-patient comparisons found systematic between-platform differences; no adequately powered comparison of major commercial platforms was identified. Abstract-level mapping of the 307 additional records identified no randomized outcome, observed decision-impact or photon-counting prognostic study. Conclusions: AI-derived plaque measures carry prognostic information in symptomatic patients, but randomized evidence that AI-guided treatment reduces myocardial infarction or cardiovascular death in asymptomatic adults, or does so better than coronary artery calcium (CAC)-guided prevention, has not been established in the sources searched and assessed. Under the modeled effects, demonstrating benefit in the lowest-burden stage would need an impractically large trial; as a design proposal, we outline a stage-enriched randomized trial. AI-assisted plaque characterization is best understood as a throughput and within-system repeatability technology; cross-platform portability is not demonstrated, and it is not a validated treatment decision rule. 2026-11-09 Diagnostics, Vol. 16, Pages 3703: Reproducibility Before Treatment Decision Rules: A Targeted Scoping Review of AI-Assisted Coronary Plaque Characterization

Diagnostics doi: 10.3390/diagnostics16213703

Authors: Mingyang Qin Negin Moghadasi Ahmadreza Ghasemiesfe Misagh Piran

Background/Objectives: Coronary computed tomography angiography (CCTA) can quantify plaque, whose burden predicts myocardial infarction better than stenosis severity. We reviewed evidence for artificial intelligence (AI)-assisted plaque characterization. Methods: This targeted scoping review (PRISMA-ScR) used a non-exhaustive search, mainly of MEDLINE/PubMed (July 2026, supplemented in September). AI title selection (135 of 1415 titles) and author assessment of 141 records yielded 121 included records under the revised criteria. An AI re-screen of 1280 unselected records (blind second pass on 175) found 110 further eligible records after charting; two AI passes screened 3634 confirmatory records (κ 0.93). The corresponding author accepted AI recommendations after reviewing written assessments, not blind (for the 335 confirmatory records, in one instruction). Of the 543 eligible records, 236 were charted (121 + 110 + 4 + 1; full text for 121 of the 236, abstract alone for 115) and 307 mapped from abstracts only (not fully charted). Results: In symptomatic or referred patients, AI-derived plaque burden was associated with major adverse cardiovascular events (a property of the measurement, not evidence that AI improves outcomes). In one comparison, AI modestly improved discrimination over manual quantification (AUC 0.82 vs. 0.78) without significant net reclassification improvement. No randomized trial of AI-based plaque analysis reporting clinical endpoints was identified in the sources searched and assessed; TRANSFORM (NCT06112418) is recruiting. Three small same-patient comparisons found systematic between-platform differences; no adequately powered comparison of major commercial platforms was identified. Abstract-level mapping of the 307 additional records identified no randomized outcome, observed decision-impact or photon-counting prognostic study. Conclusions: AI-derived plaque measures carry prognostic information in symptomatic patients, but randomized evidence that AI-guided treatment reduces myocardial infarction or cardiovascular death in asymptomatic adults, or does so better than coronary artery calcium (CAC)-guided prevention, has not been established in the sources searched and assessed. Under the modeled effects, demonstrating benefit in the lowest-burden stage would need an impractically large trial; as a design proposal, we outline a stage-enriched randomized trial. AI-assisted plaque characterization is best understood as a throughput and within-system repeatability technology; cross-platform portability is not demonstrated, and it is not a validated treatment decision rule.

]]> Reproducibility Before Treatment Decision Rules: A Targeted Scoping Review of AI-Assisted Coronary Plaque Characterization Mingyang Qin Negin Moghadasi Ahmadreza Ghasemiesfe Misagh Piran doi: 10.3390/diagnostics16213703 Diagnostics 2026-11-09 Diagnostics 2026-11-09 16 21 Review 3703 10.3390/diagnostics16213703 https://www.mdpi.com/2075-4418/16/21/3703 Diagnostics, Vol. 16, Pages 3702: Urgent Endovascular Treatment of a Pancreatitis-Related Pseudoaneurysm Identified on Follow-Up CT https://www.mdpi.com/2075-4418/16/21/3702 Visceral artery pseudoaneurysm (VA-PSA) is an uncommon but life-threatening complication of acute-on-chronic pancreatitis, particularly in the presence of walled-off necrosis (WON). Early radiological recognition is essential because of the high risk of rupture. We present the case of a 51-year-old man with chronic pancreatitis who developed a pseudoaneurysm arising from the proper hepatic artery within a pancreatic head necrotic collection. Follow-up contrast-enhanced computed tomography (CT) demonstrated a new arterial-phase enhancing focus within the WON. Digital subtraction angiography (DSA) confirmed the pseudoaneurysm, which was successfully excluded with a covered stent placed via a right transfemoral approach. Post-procedural recovery was uneventful, and short-term follow-up CT showed persistent exclusion of the lesion. 2026-11-09 Diagnostics, Vol. 16, Pages 3702: Urgent Endovascular Treatment of a Pancreatitis-Related Pseudoaneurysm Identified on Follow-Up CT

Diagnostics doi: 10.3390/diagnostics16213702

Authors: Vladimir Cvetic Sonja Lukendic Milica Mitrovic Aleksandra Jankovic Borivoje Lukic Aleksandar Bogdanovic Predrag Zdujic Dejan Radenkovic Jelena Djokic Kovac

Visceral artery pseudoaneurysm (VA-PSA) is an uncommon but life-threatening complication of acute-on-chronic pancreatitis, particularly in the presence of walled-off necrosis (WON). Early radiological recognition is essential because of the high risk of rupture. We present the case of a 51-year-old man with chronic pancreatitis who developed a pseudoaneurysm arising from the proper hepatic artery within a pancreatic head necrotic collection. Follow-up contrast-enhanced computed tomography (CT) demonstrated a new arterial-phase enhancing focus within the WON. Digital subtraction angiography (DSA) confirmed the pseudoaneurysm, which was successfully excluded with a covered stent placed via a right transfemoral approach. Post-procedural recovery was uneventful, and short-term follow-up CT showed persistent exclusion of the lesion.

]]> Urgent Endovascular Treatment of a Pancreatitis-Related Pseudoaneurysm Identified on Follow-Up CT Vladimir Cvetic Sonja Lukendic Milica Mitrovic Aleksandra Jankovic Borivoje Lukic Aleksandar Bogdanovic Predrag Zdujic Dejan Radenkovic Jelena Djokic Kovac doi: 10.3390/diagnostics16213702 Diagnostics 2026-11-09 Diagnostics 2026-11-09 16 21 Interesting Images 3702 10.3390/diagnostics16213702 https://www.mdpi.com/2075-4418/16/21/3702 Diagnostics, Vol. 16, Pages 3701: Beyond a Symptom: A Mechanism-Based Multidisciplinary Framework for the Diagnosis and Management of Chronic Cough https://www.mdpi.com/2075-4418/16/21/3701 Chronic cough may persist despite appropriate treatment of associated conditions, creating uncertainty about the relevance of coexisting abnormalities and therapeutic priorities. This evidence-informed narrative review draws on searches of PubMed/MEDLINE, Scopus, and Web of Science and relevant guidelines to propose a mechanism-based multidisciplinary framework for adults, particularly those with refractory or unexplained chronic cough. The nine-step pathway integrates established disease assessment, characterization of cough hypersensitivity and laryngeal involvement, provisional weighting of treatable traits and modifiable contributors, targeted multidisciplinary input, individualized intervention, and reassessment. Within this proposed framework, findings are considered dominant, contributory, incidental, or currently inactive according to converging clinical evidence; insufficiently evaluated findings remain uncertain. Treatment response is interpreted by distinguishing improvement in the targeted trait from improvement in cough. Discordant or inadequate responses prompt reassessment of treatment adequacy and mechanistic relevance. Patient-reported outcomes, objective cough monitoring when available, and trait-specific measures inform treatment evaluation and subsequent re-phenotyping. The weighting categories and integrated pathway represent the authors’ conceptual synthesis and have not been prospectively validated. Their reproducibility, feasibility, clinical effectiveness, and cost-effectiveness require evaluation. 2026-11-09 Diagnostics, Vol. 16, Pages 3701: Beyond a Symptom: A Mechanism-Based Multidisciplinary Framework for the Diagnosis and Management of Chronic Cough

Diagnostics doi: 10.3390/diagnostics16213701

Authors: Engin Dursun Emine Elif Altuntaş Haldun Oğuz Selmin Karataylı Özgürsoy Esma Altan Saime Güzelsoy Sağıroğlu Yusuf Aydemir Güleser Saylam Adile Berna Dursun Celil Göçer

Chronic cough may persist despite appropriate treatment of associated conditions, creating uncertainty about the relevance of coexisting abnormalities and therapeutic priorities. This evidence-informed narrative review draws on searches of PubMed/MEDLINE, Scopus, and Web of Science and relevant guidelines to propose a mechanism-based multidisciplinary framework for adults, particularly those with refractory or unexplained chronic cough. The nine-step pathway integrates established disease assessment, characterization of cough hypersensitivity and laryngeal involvement, provisional weighting of treatable traits and modifiable contributors, targeted multidisciplinary input, individualized intervention, and reassessment. Within this proposed framework, findings are considered dominant, contributory, incidental, or currently inactive according to converging clinical evidence; insufficiently evaluated findings remain uncertain. Treatment response is interpreted by distinguishing improvement in the targeted trait from improvement in cough. Discordant or inadequate responses prompt reassessment of treatment adequacy and mechanistic relevance. Patient-reported outcomes, objective cough monitoring when available, and trait-specific measures inform treatment evaluation and subsequent re-phenotyping. The weighting categories and integrated pathway represent the authors’ conceptual synthesis and have not been prospectively validated. Their reproducibility, feasibility, clinical effectiveness, and cost-effectiveness require evaluation.

]]> Beyond a Symptom: A Mechanism-Based Multidisciplinary Framework for the Diagnosis and Management of Chronic Cough Engin Dursun Emine Elif Altuntaş Haldun Oğuz Selmin Karataylı Özgürsoy Esma Altan Saime Güzelsoy Sağıroğlu Yusuf Aydemir Güleser Saylam Adile Berna Dursun Celil Göçer doi: 10.3390/diagnostics16213701 Diagnostics 2026-11-09 Diagnostics 2026-11-09 16 21 Review 3701 10.3390/diagnostics16213701 https://www.mdpi.com/2075-4418/16/21/3701 Diagnostics, Vol. 16, Pages 3700: Serum Asprosin Concentrations and Severity in Acute Pancreatitis: A Prospective Case–Control Study with Serial Measurements https://www.mdpi.com/2075-4418/16/21/3700 Background/Objectives: Asprosin is a fasting-induced glucogenic adipokine with pro-inflammatory effects in experimental models, but its behaviour in acute pancreatitis (AP) is unknown. In this exploratory study, we examined whether circulating asprosin differs between patients with AP and healthy controls, how it changes during hospitalisation and whether it is associated with disease severity. Methods: In this prospective case–control study, 82 patients with AP (of 183 screened, after exclusion of diabetes, hypertriglyceridaemia and morbid obesity) and 82 sex-matched healthy controls were enrolled. Serum asprosin was measured by ELISA at admission, 72 h and 120 h in patients and once in fasting controls. Severity was defined by the revised Atlanta classification. Because patients were older and heavier than controls, the group difference was adjusted for age, body mass index and sex and examined in post hoc matched subsamples. Results: Admission asprosin was 4.52 (2.94–5.89) ng/mL in patients and 3.55 (2.24–4.92) ng/mL in controls (p = 0.071); the ratio of geometric means adjusted for age, body mass index and sex was 1.17 (95% CI 0.85–1.61). Asprosin was higher in patients in post hoc age- and sex-matched pairs (median difference 1.91 ng/mL, 95% CI 0.24–3.78) but not in body mass index- and sex-matched pairs (0.96 ng/mL, −0.34 to 2.72). Asprosin changed little over five days and was not associated with moderately severe or severe AP (AUC 0.57, upper 95% confidence limits ≤0.71); only seven patients had severe AP. Conclusions: In this exploratory study, serum asprosin was modestly and non-significantly higher in patients with AP than in controls, and no statistically significant association with severity was detected. Residual confounding by age and body mass index, the exclusion of patients with diabetes or hypertriglyceridaemia (≥200 mg/dL) and the absence of in-house assay validation preclude firm conclusions. These data provide effect estimates for adequately powered, matched studies of asprosin in AP. 2026-11-09 Diagnostics, Vol. 16, Pages 3700: Serum Asprosin Concentrations and Severity in Acute Pancreatitis: A Prospective Case–Control Study with Serial Measurements

Diagnostics doi: 10.3390/diagnostics16213700

Authors: Mehmet Fatih Uzanulu Musa Ak Levent Bolat Onur Selçuk Yiğit Cihat Uçar Hacı Mehmet Çitil Handan Kanat Seyhan

Background/Objectives: Asprosin is a fasting-induced glucogenic adipokine with pro-inflammatory effects in experimental models, but its behaviour in acute pancreatitis (AP) is unknown. In this exploratory study, we examined whether circulating asprosin differs between patients with AP and healthy controls, how it changes during hospitalisation and whether it is associated with disease severity. Methods: In this prospective case–control study, 82 patients with AP (of 183 screened, after exclusion of diabetes, hypertriglyceridaemia and morbid obesity) and 82 sex-matched healthy controls were enrolled. Serum asprosin was measured by ELISA at admission, 72 h and 120 h in patients and once in fasting controls. Severity was defined by the revised Atlanta classification. Because patients were older and heavier than controls, the group difference was adjusted for age, body mass index and sex and examined in post hoc matched subsamples. Results: Admission asprosin was 4.52 (2.94–5.89) ng/mL in patients and 3.55 (2.24–4.92) ng/mL in controls (p = 0.071); the ratio of geometric means adjusted for age, body mass index and sex was 1.17 (95% CI 0.85–1.61). Asprosin was higher in patients in post hoc age- and sex-matched pairs (median difference 1.91 ng/mL, 95% CI 0.24–3.78) but not in body mass index- and sex-matched pairs (0.96 ng/mL, −0.34 to 2.72). Asprosin changed little over five days and was not associated with moderately severe or severe AP (AUC 0.57, upper 95% confidence limits ≤0.71); only seven patients had severe AP. Conclusions: In this exploratory study, serum asprosin was modestly and non-significantly higher in patients with AP than in controls, and no statistically significant association with severity was detected. Residual confounding by age and body mass index, the exclusion of patients with diabetes or hypertriglyceridaemia (≥200 mg/dL) and the absence of in-house assay validation preclude firm conclusions. These data provide effect estimates for adequately powered, matched studies of asprosin in AP.

]]> Serum Asprosin Concentrations and Severity in Acute Pancreatitis: A Prospective Case–Control Study with Serial Measurements Mehmet Fatih Uzanulu Musa Ak Levent Bolat Onur Selçuk Yiğit Cihat Uçar Hacı Mehmet Çitil Handan Kanat Seyhan doi: 10.3390/diagnostics16213700 Diagnostics 2026-11-09 Diagnostics 2026-11-09 16 21 Article 3700 10.3390/diagnostics16213700 https://www.mdpi.com/2075-4418/16/21/3700 Diagnostics, Vol. 16, Pages 3699: Ranking Features Distinguish Vestibular Migraine with Positional Vertigo from Benign Paroxysmal Positional Vertigo Using Machine Learning https://www.mdpi.com/2075-4418/16/21/3699 Objectives: Vestibular migraine with positional vertigo (VMwPV) can mimic benign paroxysmal positional vertigo (BPPV), leading to diagnostic challenges. This study aimed to compare clinical and nystagmus-related features between VMwPV and BPPV patients and to establish a differential diagnostic model using machine learning. Methods: 101 VMwPV and 219 BPPV patients were enrolled. The nystagmus-related features included spontaneous nystagmus (SN) and parameters during positional testing: latency, pure vertical or vertical-component positional nystagmus (PN), PN lasting <1 min, and the maximum slow phase velocity (SPVmax) of PN. Vertigo/dizziness during positional testing was also included. Using multiple machine learning algorithms, diagnostic models were constructed, and the optimal model was selected. The Shapley Additive Explanations (SHAP) analysis was applied to rank the feature importance. Results: (1) Compared with BPPV, VMwPV patients were more likely to have SN and pure vertical/vertical-component PN but less likely to have latency, PN lasting <1 min, and provoked vertigo/dizziness; the SPVmax of PN was lower in VMwPV than in BPPV. (2) No statistically significant differences in area under the curve (AUC) were observed among the five models. Logistic Regression was selected as the optimal model based on its superior interpretability. (3) Vertigo/dizziness during positional testing and PN lasting <1 min were ranked as the top two most important features based on SHAP analysis. These findings should be interpreted with caution due to group selection and incorporation bias. Conclusions: Apart from the subjective provoked vertigo/dizziness, other objective variables such as PN lasting <1 min may have potential value in differentiating VMwPV and BPPV, which require multicenter studies and prospective external validation. 2026-11-09 Diagnostics, Vol. 16, Pages 3699: Ranking Features Distinguish Vestibular Migraine with Positional Vertigo from Benign Paroxysmal Positional Vertigo Using Machine Learning

Diagnostics doi: 10.3390/diagnostics16213699

Authors: Kaijun Xia Linlin Wang Xingqian Shen Xiaoye Chen Ziying Xu Xuanyu Shi Lu Wang Hongchang Wang Hongjun Xiao Bo Liu Yangming Leng

Objectives: Vestibular migraine with positional vertigo (VMwPV) can mimic benign paroxysmal positional vertigo (BPPV), leading to diagnostic challenges. This study aimed to compare clinical and nystagmus-related features between VMwPV and BPPV patients and to establish a differential diagnostic model using machine learning. Methods: 101 VMwPV and 219 BPPV patients were enrolled. The nystagmus-related features included spontaneous nystagmus (SN) and parameters during positional testing: latency, pure vertical or vertical-component positional nystagmus (PN), PN lasting <1 min, and the maximum slow phase velocity (SPVmax) of PN. Vertigo/dizziness during positional testing was also included. Using multiple machine learning algorithms, diagnostic models were constructed, and the optimal model was selected. The Shapley Additive Explanations (SHAP) analysis was applied to rank the feature importance. Results: (1) Compared with BPPV, VMwPV patients were more likely to have SN and pure vertical/vertical-component PN but less likely to have latency, PN lasting <1 min, and provoked vertigo/dizziness; the SPVmax of PN was lower in VMwPV than in BPPV. (2) No statistically significant differences in area under the curve (AUC) were observed among the five models. Logistic Regression was selected as the optimal model based on its superior interpretability. (3) Vertigo/dizziness during positional testing and PN lasting <1 min were ranked as the top two most important features based on SHAP analysis. These findings should be interpreted with caution due to group selection and incorporation bias. Conclusions: Apart from the subjective provoked vertigo/dizziness, other objective variables such as PN lasting <1 min may have potential value in differentiating VMwPV and BPPV, which require multicenter studies and prospective external validation.

]]> Ranking Features Distinguish Vestibular Migraine with Positional Vertigo from Benign Paroxysmal Positional Vertigo Using Machine Learning Kaijun Xia Linlin Wang Xingqian Shen Xiaoye Chen Ziying Xu Xuanyu Shi Lu Wang Hongchang Wang Hongjun Xiao Bo Liu Yangming Leng doi: 10.3390/diagnostics16213699 Diagnostics 2026-11-09 Diagnostics 2026-11-09 16 21 Article 3699 10.3390/diagnostics16213699 https://www.mdpi.com/2075-4418/16/21/3699 Diagnostics, Vol. 16, Pages 3698: An Evidence Map of Pupillary Assessment in a Preselected Acute-Care Literature Archive https://www.mdpi.com/2075-4418/16/21/3698 Background/Objectives: We examined clinical purpose and acquisition method in a preselected acute-care archive of unknown representativeness. Methods: We reconciled 871 historical records using numerical adult-age evidence. Historical dual-human review, investigator-adopted dispositions for 325 unresolved records, a separate 100-record human-verified audit, and source reconciliation were distinguished. Six mapping domains and a scenario adding 274 age-unverified reports were analyzed. Results: The archive contained 355 core reports, 15 noncore records, 497 eligibility exclusions, three unresolved sources and one duplicate. Acquisition remained unestablished in 237/355 reports (66.8%): 38 remained unresolved after targeted source reconciliation, and 199 were not sampled for that acquisition audit. Any automated component was documented in 17/39 cardiac-arrest reports (43.6%), 15/27 mixed neurological/trauma reports (55.6%), and 6/116 trauma reports (5.2%). Diagnostic/physiological questions predominated in ocular and toxicological reports; neurological prognosis predominated after cardiac arrest. Adding age-unverified reports increased trauma representation from 32.7% to 39.9%. Conclusions: Clinical questions and documented acquisition profiles differ within this archive, while the numerical-age rule changes case mix. Unestablished acquisition and unequal verification limit comparisons of documented assessment methods across clinical groups. These findings do not establish field-wide coverage, clinical adoption, or comparative effectiveness. 2026-11-09 Diagnostics, Vol. 16, Pages 3698: An Evidence Map of Pupillary Assessment in a Preselected Acute-Care Literature Archive

Diagnostics doi: 10.3390/diagnostics16213698

Authors: Cheng-Yueh Li Chiao-Yin Cheng Chih-Jung Chang Hua Ho Yao-Jen Liang Jen-Tang Sun

Background/Objectives: We examined clinical purpose and acquisition method in a preselected acute-care archive of unknown representativeness. Methods: We reconciled 871 historical records using numerical adult-age evidence. Historical dual-human review, investigator-adopted dispositions for 325 unresolved records, a separate 100-record human-verified audit, and source reconciliation were distinguished. Six mapping domains and a scenario adding 274 age-unverified reports were analyzed. Results: The archive contained 355 core reports, 15 noncore records, 497 eligibility exclusions, three unresolved sources and one duplicate. Acquisition remained unestablished in 237/355 reports (66.8%): 38 remained unresolved after targeted source reconciliation, and 199 were not sampled for that acquisition audit. Any automated component was documented in 17/39 cardiac-arrest reports (43.6%), 15/27 mixed neurological/trauma reports (55.6%), and 6/116 trauma reports (5.2%). Diagnostic/physiological questions predominated in ocular and toxicological reports; neurological prognosis predominated after cardiac arrest. Adding age-unverified reports increased trauma representation from 32.7% to 39.9%. Conclusions: Clinical questions and documented acquisition profiles differ within this archive, while the numerical-age rule changes case mix. Unestablished acquisition and unequal verification limit comparisons of documented assessment methods across clinical groups. These findings do not establish field-wide coverage, clinical adoption, or comparative effectiveness.

]]> An Evidence Map of Pupillary Assessment in a Preselected Acute-Care Literature Archive Cheng-Yueh Li Chiao-Yin Cheng Chih-Jung Chang Hua Ho Yao-Jen Liang Jen-Tang Sun doi: 10.3390/diagnostics16213698 Diagnostics 2026-11-09 Diagnostics 2026-11-09 16 21 Review 3698 10.3390/diagnostics16213698 https://www.mdpi.com/2075-4418/16/21/3698 Diagnostics, Vol. 16, Pages 3697: Ultra-High-Resolution Imaging of Rectal Cancer with Photon-Counting Detector Computed Tomography: An Exploratory Pilot Study on the Impact of Slice Thickness and Monoenergetic Reconstruction Level on Image Quality https://www.mdpi.com/2075-4418/16/21/3697 Background/Objectives: To evaluate, in an exploratory pilot study, the influence of slice thickness and monoenergetic (ME) level on quantitative and qualitative image quality of ultra-high-resolution (UHR) photon-counting detector CT (PCD-CT) in rectal cancer (RC). Methods: This prospective pilot study enrolled 21 patients with suspected RC undergoing pre-treatment PCD-CT between July 2023 and February 2025. All underwent a QuantumPlus portal venous phase, whose 3 mm/60 keV reconstruction served as the standard reference, plus a separate pelvic UHR acquisition. Sixteen UHR reconstructions were generated (0.6–3 mm; 45–70 keV). Signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and noise were analyzed using linear mixed-effects models. Three readers independently rated overall image quality, perceived noise, mesorectal fascia (MRF) sharpness and lesion conspicuity relative to the reference; ratings were analyzed using mixed model ordinal regression. The primary analysis was the within-UHR comparison of reconstruction settings; the comparison with the reference, which differed in contrast phase and acquisition parameters, was descriptive. Results: Nineteen patients (mean age 61.7 ± 10.7 years, 73.7% male) were included. CNR showed a significant slice thickness–ME level interaction (p < 0.001), ranging from 4.85 ± 2.43 (3 mm/45 keV) to 0.86 ± 1.04 (0.6 mm/70 keV). SNR increased and noise decreased with thicker slices, while both decreased with higher ME levels (all p < 0.001). ME level influenced all four qualitative parameters (all p < 0.001); slice thickness significantly affected overall quality and perceived noise (p < 0.001) but not MRF sharpness or lesion conspicuity (p ≥ 0.115). Overall quality was rated favorably in 82.9% at 70 keV versus 45.6% at 45 keV. Lesion conspicuity reached 71.9–86.0% favorable ratings, whereas perceived noise was consistently rated worse than the reference, and UHR SNR remained below the reference in all settings. In a descriptive pooled summary, 3 mm/60 keV (68.0%) and 2 mm/70 keV (66.2%) were rated favorably most often, with overlapping confidence intervals. Conclusions: Slice thickness and ME level markedly influence UHR PCD-CT image quality in RC. One candidate working reconstruction for future validation is 3 mm at 60 keV, with 2 mm at 70 keV as a plausible alternative. Because the reference differed in acquisition and contrast phase and no diagnostic endpoint was assessed, these results do not establish a diagnostic benefit of UHR PCD-CT. 2026-11-09 Diagnostics, Vol. 16, Pages 3697: Ultra-High-Resolution Imaging of Rectal Cancer with Photon-Counting Detector Computed Tomography: An Exploratory Pilot Study on the Impact of Slice Thickness and Monoenergetic Reconstruction Level on Image Quality

Diagnostics doi: 10.3390/diagnostics16213697

Authors: Alexander Herold Andreas Strassl Daniela Beitzke Philipp Stelzer Christian Wassipaul Theresa Dachs Bence Nemeth Florian Lindenlaub Ahmed Ba-Ssalamah Johannes Laengle Michael Bergmann Michael Weber Dietmar Tamandl Michael A. Arnoldner

Background/Objectives: To evaluate, in an exploratory pilot study, the influence of slice thickness and monoenergetic (ME) level on quantitative and qualitative image quality of ultra-high-resolution (UHR) photon-counting detector CT (PCD-CT) in rectal cancer (RC). Methods: This prospective pilot study enrolled 21 patients with suspected RC undergoing pre-treatment PCD-CT between July 2023 and February 2025. All underwent a QuantumPlus portal venous phase, whose 3 mm/60 keV reconstruction served as the standard reference, plus a separate pelvic UHR acquisition. Sixteen UHR reconstructions were generated (0.6–3 mm; 45–70 keV). Signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and noise were analyzed using linear mixed-effects models. Three readers independently rated overall image quality, perceived noise, mesorectal fascia (MRF) sharpness and lesion conspicuity relative to the reference; ratings were analyzed using mixed model ordinal regression. The primary analysis was the within-UHR comparison of reconstruction settings; the comparison with the reference, which differed in contrast phase and acquisition parameters, was descriptive. Results: Nineteen patients (mean age 61.7 ± 10.7 years, 73.7% male) were included. CNR showed a significant slice thickness–ME level interaction (p < 0.001), ranging from 4.85 ± 2.43 (3 mm/45 keV) to 0.86 ± 1.04 (0.6 mm/70 keV). SNR increased and noise decreased with thicker slices, while both decreased with higher ME levels (all p < 0.001). ME level influenced all four qualitative parameters (all p < 0.001); slice thickness significantly affected overall quality and perceived noise (p < 0.001) but not MRF sharpness or lesion conspicuity (p ≥ 0.115). Overall quality was rated favorably in 82.9% at 70 keV versus 45.6% at 45 keV. Lesion conspicuity reached 71.9–86.0% favorable ratings, whereas perceived noise was consistently rated worse than the reference, and UHR SNR remained below the reference in all settings. In a descriptive pooled summary, 3 mm/60 keV (68.0%) and 2 mm/70 keV (66.2%) were rated favorably most often, with overlapping confidence intervals. Conclusions: Slice thickness and ME level markedly influence UHR PCD-CT image quality in RC. One candidate working reconstruction for future validation is 3 mm at 60 keV, with 2 mm at 70 keV as a plausible alternative. Because the reference differed in acquisition and contrast phase and no diagnostic endpoint was assessed, these results do not establish a diagnostic benefit of UHR PCD-CT.

]]> Ultra-High-Resolution Imaging of Rectal Cancer with Photon-Counting Detector Computed Tomography: An Exploratory Pilot Study on the Impact of Slice Thickness and Monoenergetic Reconstruction Level on Image Quality Alexander Herold Andreas Strassl Daniela Beitzke Philipp Stelzer Christian Wassipaul Theresa Dachs Bence Nemeth Florian Lindenlaub Ahmed Ba-Ssalamah Johannes Laengle Michael Bergmann Michael Weber Dietmar Tamandl Michael A. Arnoldner doi: 10.3390/diagnostics16213697 Diagnostics 2026-11-09 Diagnostics 2026-11-09 16 21 Article 3697 10.3390/diagnostics16213697 https://www.mdpi.com/2075-4418/16/21/3697 Diagnostics, Vol. 16, Pages 3696: AI-Supported Semiquantitative CT Characterization of COVID-19 Pneumonia Across SARS-CoV-2 Wild-Type, Alpha, and Delta Variants and Its Association with Clinical Parameters https://www.mdpi.com/2075-4418/16/21/3696 Objective: An AI-based software prototype for the detection of coronavirus disease 2019 (COVID-19) pneumonia was evaluated regarding its potential to quantify pulmonary opacities across Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variant groups, incorporating clinical and radiological parameters to facilitate faster diagnosis and therapy. Methods: Chest computed tomography (CT) examinations of 255 patients with confirmed COVID-19 pneumonia were analyzed using an AI-supported semiquantitative CT software prototype between November 2020 and December 2021. The results were correlated with clinical and laboratory parameters. The cohort consisted of wild-type (n = 93), Alpha (n = 66), Beta/Gamma (n = 3), and Delta (n = 93). Beta/Gamma cases were excluded from subgroup comparisons due to the small number of patients. Results: The mean AI-derived COVID-19 probability was 0.84 ± 0.33. After exclusion of five technically non-evaluable measurements, global mean opacity attenuation differed significantly among the wild-type (−475.12 ± 116.47 Hounsfield Units (HU)), Alpha (−464.68 ± 114.80 HU), and Delta groups (−423.92 ± 112.56 HU; Kruskal–Wallis H(2) = 12.062, p = 0.002). The Volume of Opacity showed no significant differences between wild-type (984.64 ± 908.92 mL), Alpha (1161.17 ± 933.55 mL), and Delta (988.19 ± 866.20 mL) (p = 0.339). The extent of pulmonary involvement (Volume of Opacity) correlated with the duration of hospital stay (r = 0.311, p < 0.001**), duration of intensive care treatment (r = 0.468, p < 0.001**), and the laboratory parameters CRP, leukocyte count, relative lymphocyte count, and AST (p < 0.001**). It showed no significant correlation with the duration of invasive ventilation (p > 0.05). A total of 37 (14.5%) patients died and 92 (36.1%) required intensive care unit (ICU) admission. Manual corrections of lung lobe and infiltrate boundaries were performed in 221/255 datasets and were required in all assessed datasets (221/221, 100%). Conclusions: The CT Pneumonia Analysis Prototype enabled semiquantitative assessment of pulmonary opacities across different SARS-CoV-2 variants but required radiological oversight and manual correction of the automated segmentations. Given the retrospective observational design, the findings should be interpreted in light of potential confounding and heterogeneity in CT acquisition protocols. The observed associations suggest that combining semiquantitative CT parameters with clinical and laboratory data may be of potential relevance for future prognostic models, which requires further evaluation in multivariable analyses. 2026-11-09 Diagnostics, Vol. 16, Pages 3696: AI-Supported Semiquantitative CT Characterization of COVID-19 Pneumonia Across SARS-CoV-2 Wild-Type, Alpha, and Delta Variants and Its Association with Clinical Parameters

Diagnostics doi: 10.3390/diagnostics16213696

Authors: Meike S. Schmidberger Stefan A. Schmidt Susanne Martina Büttner Franziska Flack Bettina Jungwirth Beate Grüner Steffen Stenger Thomas Stamminger Meinrad Beer

Objective: An AI-based software prototype for the detection of coronavirus disease 2019 (COVID-19) pneumonia was evaluated regarding its potential to quantify pulmonary opacities across Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variant groups, incorporating clinical and radiological parameters to facilitate faster diagnosis and therapy. Methods: Chest computed tomography (CT) examinations of 255 patients with confirmed COVID-19 pneumonia were analyzed using an AI-supported semiquantitative CT software prototype between November 2020 and December 2021. The results were correlated with clinical and laboratory parameters. The cohort consisted of wild-type (n = 93), Alpha (n = 66), Beta/Gamma (n = 3), and Delta (n = 93). Beta/Gamma cases were excluded from subgroup comparisons due to the small number of patients. Results: The mean AI-derived COVID-19 probability was 0.84 ± 0.33. After exclusion of five technically non-evaluable measurements, global mean opacity attenuation differed significantly among the wild-type (−475.12 ± 116.47 Hounsfield Units (HU)), Alpha (−464.68 ± 114.80 HU), and Delta groups (−423.92 ± 112.56 HU; Kruskal–Wallis H(2) = 12.062, p = 0.002). The Volume of Opacity showed no significant differences between wild-type (984.64 ± 908.92 mL), Alpha (1161.17 ± 933.55 mL), and Delta (988.19 ± 866.20 mL) (p = 0.339). The extent of pulmonary involvement (Volume of Opacity) correlated with the duration of hospital stay (r = 0.311, p < 0.001**), duration of intensive care treatment (r = 0.468, p < 0.001**), and the laboratory parameters CRP, leukocyte count, relative lymphocyte count, and AST (p < 0.001**). It showed no significant correlation with the duration of invasive ventilation (p > 0.05). A total of 37 (14.5%) patients died and 92 (36.1%) required intensive care unit (ICU) admission. Manual corrections of lung lobe and infiltrate boundaries were performed in 221/255 datasets and were required in all assessed datasets (221/221, 100%). Conclusions: The CT Pneumonia Analysis Prototype enabled semiquantitative assessment of pulmonary opacities across different SARS-CoV-2 variants but required radiological oversight and manual correction of the automated segmentations. Given the retrospective observational design, the findings should be interpreted in light of potential confounding and heterogeneity in CT acquisition protocols. The observed associations suggest that combining semiquantitative CT parameters with clinical and laboratory data may be of potential relevance for future prognostic models, which requires further evaluation in multivariable analyses.

]]> AI-Supported Semiquantitative CT Characterization of COVID-19 Pneumonia Across SARS-CoV-2 Wild-Type, Alpha, and Delta Variants and Its Association with Clinical Parameters Meike S. Schmidberger Stefan A. Schmidt Susanne Martina Büttner Franziska Flack Bettina Jungwirth Beate Grüner Steffen Stenger Thomas Stamminger Meinrad Beer doi: 10.3390/diagnostics16213696 Diagnostics 2026-11-09 Diagnostics 2026-11-09 16 21 Article 3696 10.3390/diagnostics16213696 https://www.mdpi.com/2075-4418/16/21/3696 Diagnostics, Vol. 16, Pages 3695: Presbylarynx Revisited: A Multidimensional Approach to Laryngeal Aging and Clinical Decision-Making https://www.mdpi.com/2075-4418/16/21/3695 Background: Presbylarynx describes the structural phenotype of an aging larynx, whereas presbyphonia refers to its clinically relevant perceptual and functional expression. Although vocal fold atrophy, bowing, and glottic insufficiency are common in older adults, their presence and severity do not consistently correspond to patient-reported voice impairments. Therefore, presbylaryngeal morphology should be interpreted within the broader context of compensatory capacity, physiological reserve, systemic health, and individual communication demands. Objective: This narrative review aims to provide a clinically oriented and multidimensional synthesis of presbylarynx, encompassing its terminology, morphological and functional characteristics, relationship with systemic aging, differential diagnosis, clinical assessment, management strategies, and emerging diagnostic and therapeutic approaches. Methods: A targeted literature search of PubMed/MEDLINE, Scopus, and Web of Science was conducted in August 2026, with additional targeted searches and citation checking during revision. Relevant systematic and narrative reviews, clinical practice guidelines, consensus statements, prospective and retrospective clinical studies, translational investigations, and landmark publications addressing the presbylarynx, presbyphonia, vocal fold atrophy, laryngeal aging, assessment, and treatment were reviewed and synthesized narratively. No formal systematic review protocol, duplicate screening, standardized data extraction, or risk-of-bias assessment was performed. Results: Presbylarynx encompasses age-related alterations in the vocal fold epithelium, lamina propria, intrinsic laryngeal musculature, and neuromuscular control, which may produce vocal fold atrophy, bowing, glottic insufficiency, and reduced vibratory efficiency. However, structural findings alone neither establish the cause of dysphonia nor determine the need for treatment. Clinical expression is modified by respiratory function, frailty, comorbidities, cognition, hearing status, compensatory behavior, and communication requirements. Assessment should integrate laryngeal morphology with patient-reported, auditory-perceptual, acoustic, aerodynamic, respiratory, and systemic findings, while excluding alternative and coexisting causes of dysphonia. Management should target meaningful functional impairment and may include observation, behavioral voice therapy, injection augmentation, durable medialization, or combined approaches within a flexible, nonlinear, and patient-centered pathway. Artificial intelligence, digital voice biomarkers, regenerative interventions, advanced biomaterials, and neuromuscular stimulation represent emerging opportunities; however, their clinical application remains limited by insufficient validation and predominantly preliminary or preclinical evidence. Conclusions: The presbylarynx is not inherently pathological or an indication for treatment. Its clinical significance emerges when age-related laryngeal changes contribute to meaningful limitations in voice function, communication, or quality of life. A multidimensional, system-aware, and function-driven approach is essential for accurate interpretation and individualized management. Future research should prioritize standardized definitions, reproducible phenotyping, comparable outcome measures, prospective comparative studies, and careful validation of new technologies. 2026-11-09 Diagnostics, Vol. 16, Pages 3695: Presbylarynx Revisited: A Multidimensional Approach to Laryngeal Aging and Clinical Decision-Making

Diagnostics doi: 10.3390/diagnostics16213695

Authors: Engin Dursun Emine Elif Altuntaş İlter Denizoğlu Güleser Saylam Celil Göçer Haldun Oğuz

Background: Presbylarynx describes the structural phenotype of an aging larynx, whereas presbyphonia refers to its clinically relevant perceptual and functional expression. Although vocal fold atrophy, bowing, and glottic insufficiency are common in older adults, their presence and severity do not consistently correspond to patient-reported voice impairments. Therefore, presbylaryngeal morphology should be interpreted within the broader context of compensatory capacity, physiological reserve, systemic health, and individual communication demands. Objective: This narrative review aims to provide a clinically oriented and multidimensional synthesis of presbylarynx, encompassing its terminology, morphological and functional characteristics, relationship with systemic aging, differential diagnosis, clinical assessment, management strategies, and emerging diagnostic and therapeutic approaches. Methods: A targeted literature search of PubMed/MEDLINE, Scopus, and Web of Science was conducted in August 2026, with additional targeted searches and citation checking during revision. Relevant systematic and narrative reviews, clinical practice guidelines, consensus statements, prospective and retrospective clinical studies, translational investigations, and landmark publications addressing the presbylarynx, presbyphonia, vocal fold atrophy, laryngeal aging, assessment, and treatment were reviewed and synthesized narratively. No formal systematic review protocol, duplicate screening, standardized data extraction, or risk-of-bias assessment was performed. Results: Presbylarynx encompasses age-related alterations in the vocal fold epithelium, lamina propria, intrinsic laryngeal musculature, and neuromuscular control, which may produce vocal fold atrophy, bowing, glottic insufficiency, and reduced vibratory efficiency. However, structural findings alone neither establish the cause of dysphonia nor determine the need for treatment. Clinical expression is modified by respiratory function, frailty, comorbidities, cognition, hearing status, compensatory behavior, and communication requirements. Assessment should integrate laryngeal morphology with patient-reported, auditory-perceptual, acoustic, aerodynamic, respiratory, and systemic findings, while excluding alternative and coexisting causes of dysphonia. Management should target meaningful functional impairment and may include observation, behavioral voice therapy, injection augmentation, durable medialization, or combined approaches within a flexible, nonlinear, and patient-centered pathway. Artificial intelligence, digital voice biomarkers, regenerative interventions, advanced biomaterials, and neuromuscular stimulation represent emerging opportunities; however, their clinical application remains limited by insufficient validation and predominantly preliminary or preclinical evidence. Conclusions: The presbylarynx is not inherently pathological or an indication for treatment. Its clinical significance emerges when age-related laryngeal changes contribute to meaningful limitations in voice function, communication, or quality of life. A multidimensional, system-aware, and function-driven approach is essential for accurate interpretation and individualized management. Future research should prioritize standardized definitions, reproducible phenotyping, comparable outcome measures, prospective comparative studies, and careful validation of new technologies.

]]> Presbylarynx Revisited: A Multidimensional Approach to Laryngeal Aging and Clinical Decision-Making Engin Dursun Emine Elif Altuntaş İlter Denizoğlu Güleser Saylam Celil Göçer Haldun Oğuz doi: 10.3390/diagnostics16213695 Diagnostics 2026-11-09 Diagnostics 2026-11-09 16 21 Review 3695 10.3390/diagnostics16213695 https://www.mdpi.com/2075-4418/16/21/3695 Diagnostics, Vol. 16, Pages 3693: Machine-Learning-Assisted Risk Stratification for Tuberculosis Infection in High-Risk Groups Receiving Immunosuppressive Therapy https://www.mdpi.com/2075-4418/16/21/3693 Background: Individuals receiving immunosuppressive therapy, solid-organ transplant recipients, household contacts of patients with tuberculosis, and healthcare workers are at increased risk of Mycobacterium tuberculosis infection and progression to tuberculosis disease. However, currently available immunological tests cannot reliably distinguish tuberculosis infection from active tuberculosis disease or predict individual progression to disease. We aimed to assess the prevalence of immunological evidence of tuberculosis infection across clinically and epidemiologically distinct risk groups and to explore the potential of machine-learning methods for individualised risk stratification. Methods: In this observational study, 544 adults aged 18–75 years were assessed between 2023 and 2026. Participants included patients with pulmonary tuberculosis, tuberculosis-facility healthcare workers, healthcare workers in the general medical network, household and occupational contacts of patients with tuberculosis, patients with rheumatic diseases receiving immunosuppressive therapy, patients undergoing assessment for heart transplantation, heart-transplant recipients, and healthy controls. Participants underwent clinical, epidemiological, radiological, and immunological assessment, including interferon-γ release assays (ELISPOT and QuantiFERON-TB Gold) and the tuberculosis recombinant allergen skin test. Individuals with positive immunological tests underwent additional assessment to exclude active tuberculosis. Exploratory logistic regression and decision-tree models were developed separately for each risk group using demographic and treatment-related variables. Model performance was estimated using repeated stratified 5-fold cross-validation (5 × 10 repeats) with bootstrap optimism correction; discrimination, calibration, sensitivity, specificity, positive and negative predictive values, Cohen’s kappa, and Matthews correlation coefficient were reported with 95% confidence intervals. Results: The prevalence of positive immunological tests was highest among heart-transplant recipients (15 [53.6%] of 28), followed by household contacts (12 [41.4%] of 29), patients undergoing pre-transplant assessment (5 [35.7%] of 14), and tuberculosis-facility healthcare workers (21 [22.6%] of 93). Positivity was lower among patients with rheumatic diseases receiving immunosuppressive therapy (11 [13.9%] of 79) and healthcare workers in the general medical network without documented tuberculosis exposure (7 [10.5%] of 68), and was 3 (4.4%) of 69 among healthy controls. Compared with healthy controls, positivity was significantly higher among tuberculosis-facility healthcare workers, household contacts, patients with rheumatic diseases, and pre-transplant and heart-transplant populations. Exploratory machine-learning analyses were performed separately for the two clinically most relevant immunosuppressed subgroups. In patients with rheumatic diseases (n = 71; 9 positive, 62 negative), pooled ROC AUC was 0.670 (95% CI 0.520–0.824, participant-level bootstrap); age showed 100% bootstrap sign consistency, whereas bDMARD treatment showed 84.6% and sex 55.0%. In the combined heart transplantation group (n = 41; 19 positive, 22 negative), pooled ROC AUC was 0.668 (95% CI 0.522–0.811); tacrolimus and everolimus showed the highest bootstrap sign consistency (100% and 97.6%, respectively); however, because tacrolimus and everolimus are administered predominantly to transplant recipients, these coefficients may partly reflect transplantation status rather than drug-specific effects. Because the heart transplantation group combines pre-transplant candidates and recipients, and because both subgroups had small numbers of events, these associations should be interpreted as exploratory and not as drug-specific causal effects. Conclusions: The prevalence of immunological evidence of tuberculosis infection varied substantially between risk groups and was particularly high among household contacts and heart-transplant recipients. The findings suggest that epidemiological exposure and the type of immunosuppressive therapy should be considered jointly when assessing tuberculosis infection risk. Exploratory machine-learning analyses suggested that treatment-related variables may contribute to individualised risk stratification in the combined heart transplantation group, but the models were developed in small, clinically heterogeneous subgroups and were not externally validated. They should therefore be regarded as hypothesis-generating. Prospective multicentre studies with longitudinal follow-up are required to determine whether integrated clinical, epidemiological, immunological, and treatment-related models can predict incident tuberculosis disease and improve targeted preventive strategies. 2026-11-09 Diagnostics, Vol. 16, Pages 3693: Machine-Learning-Assisted Risk Stratification for Tuberculosis Infection in High-Risk Groups Receiving Immunosuppressive Therapy

Diagnostics doi: 10.3390/diagnostics16213693

Authors: Anna Starshinova Adilia Sabirova Olesia Koroteeva Raul Sharipov Aleksandr Panteleev Michail Nazarenko Nikolay N. Osipov Dmitry Spelnikov Dmitry Kudlay

Background: Individuals receiving immunosuppressive therapy, solid-organ transplant recipients, household contacts of patients with tuberculosis, and healthcare workers are at increased risk of Mycobacterium tuberculosis infection and progression to tuberculosis disease. However, currently available immunological tests cannot reliably distinguish tuberculosis infection from active tuberculosis disease or predict individual progression to disease. We aimed to assess the prevalence of immunological evidence of tuberculosis infection across clinically and epidemiologically distinct risk groups and to explore the potential of machine-learning methods for individualised risk stratification. Methods: In this observational study, 544 adults aged 18–75 years were assessed between 2023 and 2026. Participants included patients with pulmonary tuberculosis, tuberculosis-facility healthcare workers, healthcare workers in the general medical network, household and occupational contacts of patients with tuberculosis, patients with rheumatic diseases receiving immunosuppressive therapy, patients undergoing assessment for heart transplantation, heart-transplant recipients, and healthy controls. Participants underwent clinical, epidemiological, radiological, and immunological assessment, including interferon-γ release assays (ELISPOT and QuantiFERON-TB Gold) and the tuberculosis recombinant allergen skin test. Individuals with positive immunological tests underwent additional assessment to exclude active tuberculosis. Exploratory logistic regression and decision-tree models were developed separately for each risk group using demographic and treatment-related variables. Model performance was estimated using repeated stratified 5-fold cross-validation (5 × 10 repeats) with bootstrap optimism correction; discrimination, calibration, sensitivity, specificity, positive and negative predictive values, Cohen’s kappa, and Matthews correlation coefficient were reported with 95% confidence intervals. Results: The prevalence of positive immunological tests was highest among heart-transplant recipients (15 [53.6%] of 28), followed by household contacts (12 [41.4%] of 29), patients undergoing pre-transplant assessment (5 [35.7%] of 14), and tuberculosis-facility healthcare workers (21 [22.6%] of 93). Positivity was lower among patients with rheumatic diseases receiving immunosuppressive therapy (11 [13.9%] of 79) and healthcare workers in the general medical network without documented tuberculosis exposure (7 [10.5%] of 68), and was 3 (4.4%) of 69 among healthy controls. Compared with healthy controls, positivity was significantly higher among tuberculosis-facility healthcare workers, household contacts, patients with rheumatic diseases, and pre-transplant and heart-transplant populations. Exploratory machine-learning analyses were performed separately for the two clinically most relevant immunosuppressed subgroups. In patients with rheumatic diseases (n = 71; 9 positive, 62 negative), pooled ROC AUC was 0.670 (95% CI 0.520–0.824, participant-level bootstrap); age showed 100% bootstrap sign consistency, whereas bDMARD treatment showed 84.6% and sex 55.0%. In the combined heart transplantation group (n = 41; 19 positive, 22 negative), pooled ROC AUC was 0.668 (95% CI 0.522–0.811); tacrolimus and everolimus showed the highest bootstrap sign consistency (100% and 97.6%, respectively); however, because tacrolimus and everolimus are administered predominantly to transplant recipients, these coefficients may partly reflect transplantation status rather than drug-specific effects. Because the heart transplantation group combines pre-transplant candidates and recipients, and because both subgroups had small numbers of events, these associations should be interpreted as exploratory and not as drug-specific causal effects. Conclusions: The prevalence of immunological evidence of tuberculosis infection varied substantially between risk groups and was particularly high among household contacts and heart-transplant recipients. The findings suggest that epidemiological exposure and the type of immunosuppressive therapy should be considered jointly when assessing tuberculosis infection risk. Exploratory machine-learning analyses suggested that treatment-related variables may contribute to individualised risk stratification in the combined heart transplantation group, but the models were developed in small, clinically heterogeneous subgroups and were not externally validated. They should therefore be regarded as hypothesis-generating. Prospective multicentre studies with longitudinal follow-up are required to determine whether integrated clinical, epidemiological, immunological, and treatment-related models can predict incident tuberculosis disease and improve targeted preventive strategies.

]]> Machine-Learning-Assisted Risk Stratification for Tuberculosis Infection in High-Risk Groups Receiving Immunosuppressive Therapy Anna Starshinova Adilia Sabirova Olesia Koroteeva Raul Sharipov Aleksandr Panteleev Michail Nazarenko Nikolay N. Osipov Dmitry Spelnikov Dmitry Kudlay doi: 10.3390/diagnostics16213693 Diagnostics 2026-11-09 Diagnostics 2026-11-09 16 21 Article 3693 10.3390/diagnostics16213693 https://www.mdpi.com/2075-4418/16/21/3693 Diagnostics, Vol. 16, Pages 3694: Coronary Collateral Circulation in Coronary Syndromes: Echocardiographic Insights and Future Perspectives https://www.mdpi.com/2075-4418/16/21/3694 Coronary collateral circulation (CCC) represents a natural adaptive mechanism capable of preserving myocardial perfusion in the presence of obstructive coronary artery disease. Although invasive angiography remains the reference method for collateral visualization, it provides limited information regarding collateral functionality and downstream myocardial protection. Echocardiography, due to its widespread availability, lack of radiation, and advances in imaging techniques, has emerged as an attractive non-invasive tool for evaluating the myocardial consequences of collateral perfusion. This review summarizes current evidence regarding the role of echocardiography in assessing coronary collateral circulation. Conventional echocardiographic parameters, stress echocardiography, myocardial contrast echocardiography, speckle-tracking imaging, myocardial work analysis and three-dimensional echocardiography are reviewed in the context of collateral-dependent myocardial function. Emerging technologies including artificial intelligence and quantitative perfusion imaging are also discussed. Rather than directly visualizing collateral vessels, echocardiography provides complementary information on the myocardial consequences of collateral-dependent perfusion through assessment of regional function, myocardial mechanics, and, with contrast techniques, tissue perfusion. However, collateral-specific validation remains limited, particularly for emerging deformation and myocardial work indices, and echocardiographic findings should be interpreted alongside coronary anatomy and physiological or perfusion measurements. Future integration with invasive assessment, multimodality imaging, and molecular markers may improve characterization of collateral-dependent myocardium. 2026-11-09 Diagnostics, Vol. 16, Pages 3694: Coronary Collateral Circulation in Coronary Syndromes: Echocardiographic Insights and Future Perspectives

Diagnostics doi: 10.3390/diagnostics16213694

Authors: Diana Zamfir Alexandra Ioana Dumitrache Diana Irena Cojocaru Alexandru Scafa-Udriște

Coronary collateral circulation (CCC) represents a natural adaptive mechanism capable of preserving myocardial perfusion in the presence of obstructive coronary artery disease. Although invasive angiography remains the reference method for collateral visualization, it provides limited information regarding collateral functionality and downstream myocardial protection. Echocardiography, due to its widespread availability, lack of radiation, and advances in imaging techniques, has emerged as an attractive non-invasive tool for evaluating the myocardial consequences of collateral perfusion. This review summarizes current evidence regarding the role of echocardiography in assessing coronary collateral circulation. Conventional echocardiographic parameters, stress echocardiography, myocardial contrast echocardiography, speckle-tracking imaging, myocardial work analysis and three-dimensional echocardiography are reviewed in the context of collateral-dependent myocardial function. Emerging technologies including artificial intelligence and quantitative perfusion imaging are also discussed. Rather than directly visualizing collateral vessels, echocardiography provides complementary information on the myocardial consequences of collateral-dependent perfusion through assessment of regional function, myocardial mechanics, and, with contrast techniques, tissue perfusion. However, collateral-specific validation remains limited, particularly for emerging deformation and myocardial work indices, and echocardiographic findings should be interpreted alongside coronary anatomy and physiological or perfusion measurements. Future integration with invasive assessment, multimodality imaging, and molecular markers may improve characterization of collateral-dependent myocardium.

]]> Coronary Collateral Circulation in Coronary Syndromes: Echocardiographic Insights and Future Perspectives Diana Zamfir Alexandra Ioana Dumitrache Diana Irena Cojocaru Alexandru Scafa-Udriște doi: 10.3390/diagnostics16213694 Diagnostics 2026-11-09 Diagnostics 2026-11-09 16 21 Review 3694 10.3390/diagnostics16213694 https://www.mdpi.com/2075-4418/16/21/3694 Diagnostics, Vol. 16, Pages 3692: A LAMP–CRISPR/Cas12a Assay for Specific Detection of Escherichia coli in Whole Blood: Analytical Performance and Clinical Evaluation in Suspected Bloodstream Infection https://www.mdpi.com/2075-4418/16/21/3692 Background/Objectives: Blood culture is slow and real-time PCR (qPCR) needs a thermal cycler, while loop-mediated isothermal amplification (LAMP) is rapid but prone to non-specific amplification. We developed a LAMP assay with CRISPR/Cas12a read-out targeting the Escherichia coli dxs gene and compared it with qPCR and blood culture. Methods: Reaction conditions were optimised and specificity tested on 15 E. coli and 40 non-target isolates. The limit of detection (LOD) was determined in spiked whole blood (20 replicates per level, 1–10 CFU/mL) by hit rate and probit regression, with conversion to dxs copies by growth phase. Fifty-two patients with suspected bloodstream infection were tested by all three methods. Results: The assay detected all 15 Escherichia coli isolates tested (inclusivity 15/15; 95% CI 79.6–100) and none of 40 non-target isolates (exclusivity 40/40; 95% CI 91.2–100); the exclusivity panel did not include Shigella spp. or Escherichia fergusonii, which the in silico analysis predicts the assay would detect. The probit LOD95 was 14.2 CFU/mL (95% fiducial limits 6.7–156; ≈43 dxs copies/mL for the mid-exponential spike culture used here) for LAMP-CRISPR/Cas12a and 5.8 CFU/mL (2.6–958) for qPCR; a positive was read within 5 min of starting the Cas12a detection step. LAMP-CRISPR/Cas12a was positive in 19/33 qPCR-positive and 0/19 qPCR-negative patients (positive and negative percent agreement 57.6% and 100%; κ = 0.50); all 13 samples at or above the qPCR LOD95 were detected. Conclusions: LAMP-CRISPR/Cas12a detects E. coli in whole blood specifically and rapidly, but its clinical sensitivity is limited by the very low bacterial loads of bacteraemia, so that it is suited to use as a rapid confirmatory test alongside blood culture rather than as a rule-out test. 2026-11-09 Diagnostics, Vol. 16, Pages 3692: A LAMP–CRISPR/Cas12a Assay for Specific Detection of Escherichia coli in Whole Blood: Analytical Performance and Clinical Evaluation in Suspected Bloodstream Infection

Diagnostics doi: 10.3390/diagnostics16213692

Authors: Dao Thanh Quyen Nguyen Sy Thau Pham Quang Trung Nguyen Quang Huy Dao Thi Huyen Phan Quoc Hoan Do Thu Trang Le Mai Parkes Le Huu Song Ngo Tat Trung

Background/Objectives: Blood culture is slow and real-time PCR (qPCR) needs a thermal cycler, while loop-mediated isothermal amplification (LAMP) is rapid but prone to non-specific amplification. We developed a LAMP assay with CRISPR/Cas12a read-out targeting the Escherichia coli dxs gene and compared it with qPCR and blood culture. Methods: Reaction conditions were optimised and specificity tested on 15 E. coli and 40 non-target isolates. The limit of detection (LOD) was determined in spiked whole blood (20 replicates per level, 1–10 CFU/mL) by hit rate and probit regression, with conversion to dxs copies by growth phase. Fifty-two patients with suspected bloodstream infection were tested by all three methods. Results: The assay detected all 15 Escherichia coli isolates tested (inclusivity 15/15; 95% CI 79.6–100) and none of 40 non-target isolates (exclusivity 40/40; 95% CI 91.2–100); the exclusivity panel did not include Shigella spp. or Escherichia fergusonii, which the in silico analysis predicts the assay would detect. The probit LOD95 was 14.2 CFU/mL (95% fiducial limits 6.7–156; ≈43 dxs copies/mL for the mid-exponential spike culture used here) for LAMP-CRISPR/Cas12a and 5.8 CFU/mL (2.6–958) for qPCR; a positive was read within 5 min of starting the Cas12a detection step. LAMP-CRISPR/Cas12a was positive in 19/33 qPCR-positive and 0/19 qPCR-negative patients (positive and negative percent agreement 57.6% and 100%; κ = 0.50); all 13 samples at or above the qPCR LOD95 were detected. Conclusions: LAMP-CRISPR/Cas12a detects E. coli in whole blood specifically and rapidly, but its clinical sensitivity is limited by the very low bacterial loads of bacteraemia, so that it is suited to use as a rapid confirmatory test alongside blood culture rather than as a rule-out test.

]]> A LAMP–CRISPR/Cas12a Assay for Specific Detection of Escherichia coli in Whole Blood: Analytical Performance and Clinical Evaluation in Suspected Bloodstream Infection Dao Thanh Quyen Nguyen Sy Thau Pham Quang Trung Nguyen Quang Huy Dao Thi Huyen Phan Quoc Hoan Do Thu Trang Le Mai Parkes Le Huu Song Ngo Tat Trung doi: 10.3390/diagnostics16213692 Diagnostics 2026-11-09 Diagnostics 2026-11-09 16 21 Article 3692 10.3390/diagnostics16213692 https://www.mdpi.com/2075-4418/16/21/3692 Diagnostics, Vol. 16, Pages 3691: Ammonia in Liver Disease: Diagnostic Utility, Preanalytical Challenges, Clinical Interpretation, and Therapeutic Implications: A Critical Narrative Review https://www.mdpi.com/2075-4418/16/21/3691 Ammonia is central to the pathogenesis of hepatic encephalopathy (HE), but blood ammonia is neither a stand-alone diagnostic test nor a reliable measure of HE grade. Its clinical value depends on the population, the question being asked, and strict control of preanalytical and analytical conditions. This critical narrative review evaluates ammonia as a diagnostic and prognostic biomarker in liver disease, with emphasis on standardised measurement, interpretation in altered mental status, selective monitoring, and the distinction between biochemical response and patient-important outcomes. Evidence was updated through 9 October 2026 and prioritised international guidelines, the 2026 International Society for Hepatic Encephalopathy and Nitrogen Metabolism consensus, randomised trials, prospective cohorts, systematic reviews, and verified trial registries. In cirrhosis, an elevated value is nonspecific and does not confirm HE, whereas a methodologically reliable normal value should prompt diagnostic reassessment. Ammonia may add prognostic information in stable and decompensated cirrhosis, but thresholds and risk models require population-specific validation and do not independently mandate treatment. In acute liver failure, arterial ammonia has a distinct role in assessing the risk of cerebral oedema. Fasting before planned testing, avoidance of fist clenching and prolonged tourniquet use, rapid chilled transport, prompt plasma separation, and timely analysis are essential for an interpretable result. Treatment should be guided primarily by clinical course, correction of precipitants, and prevention of recurrence rather than serial ammonia concentrations. Standardisation and clinically anchored diagnostic algorithms are necessary before ammonia-guided management can be adopted broadly. 2026-11-09 Diagnostics, Vol. 16, Pages 3691: Ammonia in Liver Disease: Diagnostic Utility, Preanalytical Challenges, Clinical Interpretation, and Therapeutic Implications: A Critical Narrative Review

Diagnostics doi: 10.3390/diagnostics16213691

Authors: Tamara Milovanovic Anja Tomovic Nikola Bakovic Ivana Pantic Marko Vojnovic

Ammonia is central to the pathogenesis of hepatic encephalopathy (HE), but blood ammonia is neither a stand-alone diagnostic test nor a reliable measure of HE grade. Its clinical value depends on the population, the question being asked, and strict control of preanalytical and analytical conditions. This critical narrative review evaluates ammonia as a diagnostic and prognostic biomarker in liver disease, with emphasis on standardised measurement, interpretation in altered mental status, selective monitoring, and the distinction between biochemical response and patient-important outcomes. Evidence was updated through 9 October 2026 and prioritised international guidelines, the 2026 International Society for Hepatic Encephalopathy and Nitrogen Metabolism consensus, randomised trials, prospective cohorts, systematic reviews, and verified trial registries. In cirrhosis, an elevated value is nonspecific and does not confirm HE, whereas a methodologically reliable normal value should prompt diagnostic reassessment. Ammonia may add prognostic information in stable and decompensated cirrhosis, but thresholds and risk models require population-specific validation and do not independently mandate treatment. In acute liver failure, arterial ammonia has a distinct role in assessing the risk of cerebral oedema. Fasting before planned testing, avoidance of fist clenching and prolonged tourniquet use, rapid chilled transport, prompt plasma separation, and timely analysis are essential for an interpretable result. Treatment should be guided primarily by clinical course, correction of precipitants, and prevention of recurrence rather than serial ammonia concentrations. Standardisation and clinically anchored diagnostic algorithms are necessary before ammonia-guided management can be adopted broadly.

]]> Ammonia in Liver Disease: Diagnostic Utility, Preanalytical Challenges, Clinical Interpretation, and Therapeutic Implications: A Critical Narrative Review Tamara Milovanovic Anja Tomovic Nikola Bakovic Ivana Pantic Marko Vojnovic doi: 10.3390/diagnostics16213691 Diagnostics 2026-11-09 Diagnostics 2026-11-09 16 21 Review 3691 10.3390/diagnostics16213691 https://www.mdpi.com/2075-4418/16/21/3691 Diagnostics, Vol. 16, Pages 3690: A Rare Presentation of Ranula with Supraglottic and Paraglottic Extension Managed via a Hybrid Minimally Invasive Approach https://www.mdpi.com/2075-4418/16/21/3690 A ranula is a mucus extravasation pseudocyst typically arising from the sublingual gland, usually confined to the oral floor or submandibular space. Extension into the supraglottic and paraglottic spaces by traversing or defect-bypassing the mylohyoid muscle is an exceedingly rare phenomenon that poses a significant risk of critical airway compromise. We report an exceptional case of a right-sided ranula presenting with progressive dyspnea due to extensive posterior involvement reaching the vallecula and paraglottic region. Definitive diagnosis of the plunging ranula was established through a comprehensive framework combining clinical presentation, multimodal imaging (CT, MRI, and ultrasonography), histopathological identification of a non-epithelialized lesion with mucinous extravasation, and biochemical fluid analysis via fine-needle aspiration (FNA) confirming markedly elevated levels of salivary amylase and total protein. To mitigate surgical morbidity and avoid extensive transcervical dissection, a hybrid, minimally invasive therapeutic strategy was employed, combining intraoral sublingual gland excision with postoperative percutaneous ethanol ablation for the deep paraglottic residual pseudocystic lesion. Complete resolution of the lesion was achieved without nerve injury, recurrence, or airway complications during follow-up. This case demonstrates that a sequential combination of transoral excision and ethanol ablation is a safe, effective, and organ-preserving alternative to aggressive open neck surgery for deep-extending plunging ranulas. 2026-11-09 Diagnostics, Vol. 16, Pages 3690: A Rare Presentation of Ranula with Supraglottic and Paraglottic Extension Managed via a Hybrid Minimally Invasive Approach

Diagnostics doi: 10.3390/diagnostics16213690

Authors: Jeonghyun Oh

A ranula is a mucus extravasation pseudocyst typically arising from the sublingual gland, usually confined to the oral floor or submandibular space. Extension into the supraglottic and paraglottic spaces by traversing or defect-bypassing the mylohyoid muscle is an exceedingly rare phenomenon that poses a significant risk of critical airway compromise. We report an exceptional case of a right-sided ranula presenting with progressive dyspnea due to extensive posterior involvement reaching the vallecula and paraglottic region. Definitive diagnosis of the plunging ranula was established through a comprehensive framework combining clinical presentation, multimodal imaging (CT, MRI, and ultrasonography), histopathological identification of a non-epithelialized lesion with mucinous extravasation, and biochemical fluid analysis via fine-needle aspiration (FNA) confirming markedly elevated levels of salivary amylase and total protein. To mitigate surgical morbidity and avoid extensive transcervical dissection, a hybrid, minimally invasive therapeutic strategy was employed, combining intraoral sublingual gland excision with postoperative percutaneous ethanol ablation for the deep paraglottic residual pseudocystic lesion. Complete resolution of the lesion was achieved without nerve injury, recurrence, or airway complications during follow-up. This case demonstrates that a sequential combination of transoral excision and ethanol ablation is a safe, effective, and organ-preserving alternative to aggressive open neck surgery for deep-extending plunging ranulas.

]]> A Rare Presentation of Ranula with Supraglottic and Paraglottic Extension Managed via a Hybrid Minimally Invasive Approach Jeonghyun Oh doi: 10.3390/diagnostics16213690 Diagnostics 2026-11-09 Diagnostics 2026-11-09 16 21 Interesting Images 3690 10.3390/diagnostics16213690 https://www.mdpi.com/2075-4418/16/21/3690 Diagnostics, Vol. 16, Pages 3689: PSA Dynamics, Bounce, and Biochemical Recurrence Definitions After Low-Dose-Rate Brachytherapy for Prostate Cancer: A Narrative Review with Cross-Modality Comparison https://www.mdpi.com/2075-4418/16/21/3689 Background: Prostate-specific antigen (PSA) dynamics provide the earliest indicator of treatment outcome. Understanding them, including nadir kinetics and PSA bounce, is essential for refining biochemical recurrence (BCR) definitions and guiding clinical decision making. Methods: A literature search was conducted across the PubMed, Scopus, and Web of Science databases. Backward citation chaining of selected references resulted in a final synthesis of 143 studies. Iodine-125 constitutes the primary radioisotope across the reviewed literature. Key Findings: Following low-dose-rate brachytherapy (LDR-BT), a PSA nadir < 0.2 ng/mL is strongly associated with long-term biochemical control. PSA bounce (defined as a rise ≥ 0.2 ng/mL above the current nadir with spontaneous resolution) occurs in approximately 30% to 50% of LDR-BT cohorts, with a median onset of approximately 1.5 years, a median duration of approximately 1 year, and a median amplitude < 1 ng/mL. Up to 18% of bounces exceed 2.0 ng/mL, accounting for nearly half of all early rises triggering the Phoenix criteria. Superior dosimetric parameters are associated with longer time to nadir and lower nadir values. Within LDR-BT cohorts, younger patient age is the most consistent predictor of bounce incidence, whereas between-study variation is primarily driven by differences in treatment modality. LDR-BT and hypofractionated regimens report higher bounce rates than those for conventional external beam radiotherapy, although unadjusted comparisons are confounded. Onset timing is the most useful feature distinguishing between bounce and BCR. Conclusions: Static, single cutoff BCR definitions post-LDR-BT may be suboptimal for surveillance. This observational synthesis suggests a hypothesis-generating, time-windowed approach (Phoenix definition during early follow-up (< 4 years) and an absolute threshold of PSA > 0.2 ng/mL thereafter) that requires prospective validation and is not a recommendation for clinical use. 2026-11-08 Diagnostics, Vol. 16, Pages 3689: PSA Dynamics, Bounce, and Biochemical Recurrence Definitions After Low-Dose-Rate Brachytherapy for Prostate Cancer: A Narrative Review with Cross-Modality Comparison

Diagnostics doi: 10.3390/diagnostics16213689

Authors: Nikolay Kahchiev Elenko Popov Vaska Vasileva George Dimitrov

Background: Prostate-specific antigen (PSA) dynamics provide the earliest indicator of treatment outcome. Understanding them, including nadir kinetics and PSA bounce, is essential for refining biochemical recurrence (BCR) definitions and guiding clinical decision making. Methods: A literature search was conducted across the PubMed, Scopus, and Web of Science databases. Backward citation chaining of selected references resulted in a final synthesis of 143 studies. Iodine-125 constitutes the primary radioisotope across the reviewed literature. Key Findings: Following low-dose-rate brachytherapy (LDR-BT), a PSA nadir < 0.2 ng/mL is strongly associated with long-term biochemical control. PSA bounce (defined as a rise ≥ 0.2 ng/mL above the current nadir with spontaneous resolution) occurs in approximately 30% to 50% of LDR-BT cohorts, with a median onset of approximately 1.5 years, a median duration of approximately 1 year, and a median amplitude < 1 ng/mL. Up to 18% of bounces exceed 2.0 ng/mL, accounting for nearly half of all early rises triggering the Phoenix criteria. Superior dosimetric parameters are associated with longer time to nadir and lower nadir values. Within LDR-BT cohorts, younger patient age is the most consistent predictor of bounce incidence, whereas between-study variation is primarily driven by differences in treatment modality. LDR-BT and hypofractionated regimens report higher bounce rates than those for conventional external beam radiotherapy, although unadjusted comparisons are confounded. Onset timing is the most useful feature distinguishing between bounce and BCR. Conclusions: Static, single cutoff BCR definitions post-LDR-BT may be suboptimal for surveillance. This observational synthesis suggests a hypothesis-generating, time-windowed approach (Phoenix definition during early follow-up (< 4 years) and an absolute threshold of PSA > 0.2 ng/mL thereafter) that requires prospective validation and is not a recommendation for clinical use.

]]> PSA Dynamics, Bounce, and Biochemical Recurrence Definitions After Low-Dose-Rate Brachytherapy for Prostate Cancer: A Narrative Review with Cross-Modality Comparison Nikolay Kahchiev Elenko Popov Vaska Vasileva George Dimitrov doi: 10.3390/diagnostics16213689 Diagnostics 2026-11-08 Diagnostics 2026-11-08 16 21 Review 3689 10.3390/diagnostics16213689 https://www.mdpi.com/2075-4418/16/21/3689 Diagnostics, Vol. 16, Pages 3687: CCR2 and CCR5 Expression on Tph Cells Is Associated with IL-21 and Renal Involvement in Systemic Lupus Erythematosus https://www.mdpi.com/2075-4418/16/21/3687 Background/Objectives: The increased frequency of circulating T follicular helper (cTfh) and T peripheral helper (Tph) cells in patients with systemic lupus erythematosus (SLE) and their association with higher disease activity have been reported. However, their role in the immunopathogenesis of SLE remains unclear. CCR2 and CCR5 have been identified on the surface of cTfh and Tph cells in autoimmune diseases such as Sjögren’s Disease. Methods: This study evaluates the association between CCR2+CCR5+cTfh and CCR2+CCR5+Tph cell frequencies and serum cytokine levels in patients with SLE and lupus nephritis (LN). Results: SLE patients showed higher frequencies of cTfh and Tph cells. Overall, CCR2 and CCR5 expression was higher in Tph cells than in cTfh cells. The frequency of CCR5+Tph and CCR5+cTfh cells was higher in patients with proliferative LN than in those with mixed-type LN. IL-21 correlated with the frequency of CCR2+CCR5+ Tph cells. In renal tissue, expression of CD4, CXCR5, CCR5, and CCR2 was more prominent in tubulo-interstitial areas with predominantly chronic lesions. Conclusions: Our results provide information on the expression of CCR2 and CCR5 in cTfh and Tph cells in SLE and offer insights into the association with inducing cytokines, highlighting the potential role of these cells in LN. 2026-11-08 Diagnostics, Vol. 16, Pages 3687: CCR2 and CCR5 Expression on Tph Cells Is Associated with IL-21 and Renal Involvement in Systemic Lupus Erythematosus

Diagnostics doi: 10.3390/diagnostics16213687

Authors: Katya Rocío Félix-Murray Jhonatan Velador-Mendoza Miguel Marín-Rosales Pablo C. Ortiz-Lazareno Laura Perfinka Herrera-González Diana Celeste Salazar-Camarena Noemí Espinoza-García Esther Guadalupe Corona-Sánchez María Paulina Reyes-Mata Héctor Giancarlo Torres-Nuño Claudia Azucena Palafox-Sánchez

Background/Objectives: The increased frequency of circulating T follicular helper (cTfh) and T peripheral helper (Tph) cells in patients with systemic lupus erythematosus (SLE) and their association with higher disease activity have been reported. However, their role in the immunopathogenesis of SLE remains unclear. CCR2 and CCR5 have been identified on the surface of cTfh and Tph cells in autoimmune diseases such as Sjögren’s Disease. Methods: This study evaluates the association between CCR2+CCR5+cTfh and CCR2+CCR5+Tph cell frequencies and serum cytokine levels in patients with SLE and lupus nephritis (LN). Results: SLE patients showed higher frequencies of cTfh and Tph cells. Overall, CCR2 and CCR5 expression was higher in Tph cells than in cTfh cells. The frequency of CCR5+Tph and CCR5+cTfh cells was higher in patients with proliferative LN than in those with mixed-type LN. IL-21 correlated with the frequency of CCR2+CCR5+ Tph cells. In renal tissue, expression of CD4, CXCR5, CCR5, and CCR2 was more prominent in tubulo-interstitial areas with predominantly chronic lesions. Conclusions: Our results provide information on the expression of CCR2 and CCR5 in cTfh and Tph cells in SLE and offer insights into the association with inducing cytokines, highlighting the potential role of these cells in LN.

]]> CCR2 and CCR5 Expression on Tph Cells Is Associated with IL-21 and Renal Involvement in Systemic Lupus Erythematosus Katya Rocío Félix-Murray Jhonatan Velador-Mendoza Miguel Marín-Rosales Pablo C. Ortiz-Lazareno Laura Perfinka Herrera-González Diana Celeste Salazar-Camarena Noemí Espinoza-García Esther Guadalupe Corona-Sánchez María Paulina Reyes-Mata Héctor Giancarlo Torres-Nuño Claudia Azucena Palafox-Sánchez doi: 10.3390/diagnostics16213687 Diagnostics 2026-11-08 Diagnostics 2026-11-08 16 21 Article 3687 10.3390/diagnostics16213687 https://www.mdpi.com/2075-4418/16/21/3687 Diagnostics, Vol. 16, Pages 3688: Multimodality Imaging in Contemporary Cardio-Oncology: Beyond Ejection Fraction https://www.mdpi.com/2075-4418/16/21/3688 Background: Cancer therapy-related cardiac dysfunction (CTRCD) may develop before symptoms or a measurable decline in left ventricular ejection fraction (LVEF). Surveillance therefore requires assessment beyond LVEF alone. Content: This narrative review examines cardiotoxic mechanisms, imaging findings, and treatment-specific surveillance. Transthoracic echocardiography with LVEF and global longitudinal strain remains the first-line approach. Myocardial work may provide additional information, but oncology-specific action thresholds remain unvalidated. Cardiac magnetic resonance complements echocardiography when measurements are inconclusive or tissue characterization is required. Mapping abnormalities are nonspecific and do not independently establish treatment-related injury. Nuclear imaging addresses selected diagnostic questions; fibroblast activation protein inhibitor PET remains investigational. Artificial intelligence may support image analysis and data integration, although evidence from general cardiovascular populations requires oncology-specific validation. An algorithm and surveillance matrix link clinical findings, treatment, baseline risk, imaging, and biomarkers. Conclusions: A tiered approach organizes surveillance around specific clinical questions. Earlier detection should be distinguished from demonstrated clinical benefit: evidence that imaging-guided strategies improve long-term cardiovascular outcomes remains limited. Prospective studies are needed to validate emerging markers, AI applications, and the clinical and economic effects of integrated surveillance pathways. 2026-11-08 Diagnostics, Vol. 16, Pages 3688: Multimodality Imaging in Contemporary Cardio-Oncology: Beyond Ejection Fraction

Diagnostics doi: 10.3390/diagnostics16213688

Authors: Maria Giuseppina Veglia Serena Guasti Giuseppe Romano Stefano Oliva Andrea Tedeschi Maria Laura Canale Alice Frangione Jacopo Santagata Iacopo Fabiani Francesco Piroli Francesca Musella Fabrizio Oliva Federico Nardi Massimo Grimaldi

Background: Cancer therapy-related cardiac dysfunction (CTRCD) may develop before symptoms or a measurable decline in left ventricular ejection fraction (LVEF). Surveillance therefore requires assessment beyond LVEF alone. Content: This narrative review examines cardiotoxic mechanisms, imaging findings, and treatment-specific surveillance. Transthoracic echocardiography with LVEF and global longitudinal strain remains the first-line approach. Myocardial work may provide additional information, but oncology-specific action thresholds remain unvalidated. Cardiac magnetic resonance complements echocardiography when measurements are inconclusive or tissue characterization is required. Mapping abnormalities are nonspecific and do not independently establish treatment-related injury. Nuclear imaging addresses selected diagnostic questions; fibroblast activation protein inhibitor PET remains investigational. Artificial intelligence may support image analysis and data integration, although evidence from general cardiovascular populations requires oncology-specific validation. An algorithm and surveillance matrix link clinical findings, treatment, baseline risk, imaging, and biomarkers. Conclusions: A tiered approach organizes surveillance around specific clinical questions. Earlier detection should be distinguished from demonstrated clinical benefit: evidence that imaging-guided strategies improve long-term cardiovascular outcomes remains limited. Prospective studies are needed to validate emerging markers, AI applications, and the clinical and economic effects of integrated surveillance pathways.

]]> Multimodality Imaging in Contemporary Cardio-Oncology: Beyond Ejection Fraction Maria Giuseppina Veglia Serena Guasti Giuseppe Romano Stefano Oliva Andrea Tedeschi Maria Laura Canale Alice Frangione Jacopo Santagata Iacopo Fabiani Francesco Piroli Francesca Musella Fabrizio Oliva Federico Nardi Massimo Grimaldi doi: 10.3390/diagnostics16213688 Diagnostics 2026-11-08 Diagnostics 2026-11-08 16 21 Review 3688 10.3390/diagnostics16213688 https://www.mdpi.com/2075-4418/16/21/3688 Diagnostics, Vol. 16, Pages 3686: Prognostic Factors Associated with Treatment Outcomes in Endodontic/Periodontal Lesions: A Systematic Literature Review https://www.mdpi.com/2075-4418/16/21/3686 Background/Objectives: The complex nature of endodontic/periodontal lesions complicates treatment prognosis, making long-term tooth survival challenging to predict. Identifying key prognostic factors can facilitate evidence-based clinical decision-making. This systematic review aims to evaluate the available evidence on factors associated with treatment outcomes in endodontic/periodontal lesions and to identify potential prognostic indicators. Methods: PubMed/MEDLINE, Embase, Web of Science and Cochrane Library were searched from 1 June to 1 July 2026 with no restrictions. Observational studies investigating associations between baseline prognostic factors and treatment outcomes in adults with endodontic/periodontal lesions were eligible for inclusion. Study selection and data extraction were performed independently by two reviewers. Risk of bias was assessed using the Quality In Prognosis Studies (QUIPS) tool, and certainty of evidence was evaluated using GRADE. Due to substantial methodological heterogeneity, the findings were synthesized narratively rather than through meta-analysis. Results: Four retrospective studies comprising 501 teeth were included. Risk of bias was predominantly moderate to high, and certainty of evidence was low. No single factor demonstrated directionally consistent independent association across the available adjusted analyses. Conclusions: Despite limited evidence, an overall pattern suggests that endodontic/periodontal lesion prognosis may be most frequently associated with the extent of periodontal tissue destruction and the amount of remaining periodontal support. Prospective studies using standardized endodontic/periodontal lesion definitions, outcomes and appropriately adjusted multivariable prognostic models are needed. 2026-11-08 Diagnostics, Vol. 16, Pages 3686: Prognostic Factors Associated with Treatment Outcomes in Endodontic/Periodontal Lesions: A Systematic Literature Review

Diagnostics doi: 10.3390/diagnostics16213686

Authors: Ana Kostenkova Greta Lodienė Uršulina Lyndo Eglė Zasčiurinskienė

Background/Objectives: The complex nature of endodontic/periodontal lesions complicates treatment prognosis, making long-term tooth survival challenging to predict. Identifying key prognostic factors can facilitate evidence-based clinical decision-making. This systematic review aims to evaluate the available evidence on factors associated with treatment outcomes in endodontic/periodontal lesions and to identify potential prognostic indicators. Methods: PubMed/MEDLINE, Embase, Web of Science and Cochrane Library were searched from 1 June to 1 July 2026 with no restrictions. Observational studies investigating associations between baseline prognostic factors and treatment outcomes in adults with endodontic/periodontal lesions were eligible for inclusion. Study selection and data extraction were performed independently by two reviewers. Risk of bias was assessed using the Quality In Prognosis Studies (QUIPS) tool, and certainty of evidence was evaluated using GRADE. Due to substantial methodological heterogeneity, the findings were synthesized narratively rather than through meta-analysis. Results: Four retrospective studies comprising 501 teeth were included. Risk of bias was predominantly moderate to high, and certainty of evidence was low. No single factor demonstrated directionally consistent independent association across the available adjusted analyses. Conclusions: Despite limited evidence, an overall pattern suggests that endodontic/periodontal lesion prognosis may be most frequently associated with the extent of periodontal tissue destruction and the amount of remaining periodontal support. Prospective studies using standardized endodontic/periodontal lesion definitions, outcomes and appropriately adjusted multivariable prognostic models are needed.

]]> Prognostic Factors Associated with Treatment Outcomes in Endodontic/Periodontal Lesions: A Systematic Literature Review Ana Kostenkova Greta Lodienė Uršulina Lyndo Eglė Zasčiurinskienė doi: 10.3390/diagnostics16213686 Diagnostics 2026-11-08 Diagnostics 2026-11-08 16 21 Systematic Review 3686 10.3390/diagnostics16213686 https://www.mdpi.com/2075-4418/16/21/3686 Diagnostics, Vol. 16, Pages 3685: Correlation Between Clinicopathological Findings, Cervical Smear, and HPV Results: A Retrospective Study of Women Referred for Colposcopy https://www.mdpi.com/2075-4418/16/21/3685 Background/Objectives: This study evaluated the association of cervical cytology, human papillomavirus (HPV) genotypes, and colposcopic findings with histopathological outcomes in women referred for colposcopy. Methods: This retrospective cross-sectional study included 756 women who underwent colposcopy with cervical biopsy at a tertiary center between January 2022 and June 2025 and had HPV genotyping and conventional cytology results. The primary endpoint was cervical intraepithelial neoplasia grade 2 or worse (CIN2+) on biopsy; the highest grade across biopsy and conization specimens and CIN3+ were secondary endpoints. Associations were assessed using multivariable logistic regression, and diagnostic accuracy was reported according to STARD 2015. Results: CIN2+ was found in 85 women (11.2%). HPV-16 positivity (OR: 2.87; 95% CI: 1.72–4.77), epithelial cell abnormality on cytology (OR: 4.28; 95% CI: 2.05–8.92), and positive colposcopy (OR: 3.39; 95% CI: 2.00–5.73) were independently associated with higher odds of CIN2+. Adding colposcopy to a pre-colposcopy model increased the AUC from 0.730 to 0.770 (p = 0.034; optimism-corrected 0.753). Colposcopy had a sensitivity of 71.8% (95% CI: 61.4–80.2%) and an NPV of 94.6% (95% CI: 92.1–96.3%), but 24 of 85 CIN2+ cases (28.2%) had a negative colposcopic impression; results were similar for the highest-grade endpoint (92 CIN2+ cases). Conclusions: In this referral population, HPV-16, cytological abnormality, and colposcopic impression provided complementary information on the odds of CIN2+. Because more than one-quarter of CIN2+ cases were not colposcopically apparent, a negative colposcopy should not be considered sufficient to exclude high-grade disease, particularly in women with HPV-16 positivity or abnormal cytology. Prospective validation is required before these associations are used for triage. 2026-11-07 Diagnostics, Vol. 16, Pages 3685: Correlation Between Clinicopathological Findings, Cervical Smear, and HPV Results: A Retrospective Study of Women Referred for Colposcopy

Diagnostics doi: 10.3390/diagnostics16213685

Authors: Naile Kökbudak Merve Solmaz Fahriye Kılınç Kübra Gündoğan Zeliha Çelik Pembe Oltulu

Background/Objectives: This study evaluated the association of cervical cytology, human papillomavirus (HPV) genotypes, and colposcopic findings with histopathological outcomes in women referred for colposcopy. Methods: This retrospective cross-sectional study included 756 women who underwent colposcopy with cervical biopsy at a tertiary center between January 2022 and June 2025 and had HPV genotyping and conventional cytology results. The primary endpoint was cervical intraepithelial neoplasia grade 2 or worse (CIN2+) on biopsy; the highest grade across biopsy and conization specimens and CIN3+ were secondary endpoints. Associations were assessed using multivariable logistic regression, and diagnostic accuracy was reported according to STARD 2015. Results: CIN2+ was found in 85 women (11.2%). HPV-16 positivity (OR: 2.87; 95% CI: 1.72–4.77), epithelial cell abnormality on cytology (OR: 4.28; 95% CI: 2.05–8.92), and positive colposcopy (OR: 3.39; 95% CI: 2.00–5.73) were independently associated with higher odds of CIN2+. Adding colposcopy to a pre-colposcopy model increased the AUC from 0.730 to 0.770 (p = 0.034; optimism-corrected 0.753). Colposcopy had a sensitivity of 71.8% (95% CI: 61.4–80.2%) and an NPV of 94.6% (95% CI: 92.1–96.3%), but 24 of 85 CIN2+ cases (28.2%) had a negative colposcopic impression; results were similar for the highest-grade endpoint (92 CIN2+ cases). Conclusions: In this referral population, HPV-16, cytological abnormality, and colposcopic impression provided complementary information on the odds of CIN2+. Because more than one-quarter of CIN2+ cases were not colposcopically apparent, a negative colposcopy should not be considered sufficient to exclude high-grade disease, particularly in women with HPV-16 positivity or abnormal cytology. Prospective validation is required before these associations are used for triage.

]]> Correlation Between Clinicopathological Findings, Cervical Smear, and HPV Results: A Retrospective Study of Women Referred for Colposcopy Naile Kökbudak Merve Solmaz Fahriye Kılınç Kübra Gündoğan Zeliha Çelik Pembe Oltulu doi: 10.3390/diagnostics16213685 Diagnostics 2026-11-07 Diagnostics 2026-11-07 16 21 Article 3685 10.3390/diagnostics16213685 https://www.mdpi.com/2075-4418/16/21/3685