Diagnostics

12 pages, 687 KB

Open AccessArticle

Antinuclear Antibodies Predict Treatment Escalation and Biologic Switching in Rheumatoid Arthritis

by Zeynel Abidin Akar, Dilan Yıldırım, Mehmet Çiftçi, Zeynep Işık Sula, Serap Karaman, Remzi Çevik, Mehmet Karakoç, Serda Em, İbrahim Batmaz, Pelin Oktayoğlu and Mehmet Çağlayan

Diagnostics 2026, 16(6), 957; https://doi.org/10.3390/diagnostics16060957 - 23 Mar 2026

Abstract

Background: Antinuclear antibodies (ANAs) are frequently detected in patients with rheumatoid arthritis (RA); however, their prognostic relevance for predicting treatment escalation and biologic therapy initiation remains incompletely understood. Identifying biomarkers associated with earlier transition to advanced therapies may enhance individualized, treat-to-target disease management. [...] Read more.

Background: Antinuclear antibodies (ANAs) are frequently detected in patients with rheumatoid arthritis (RA); however, their prognostic relevance for predicting treatment escalation and biologic therapy initiation remains incompletely understood. Identifying biomarkers associated with earlier transition to advanced therapies may enhance individualized, treat-to-target disease management. Objectives: We aimed to evaluate the association of ANA status and titer levels with clinical characteristics, treatment trajectories, and time to biologic therapy initiation in patients with RA. Methods: In this retrospective cohort study, 223 patients with RA were stratified according to ANA status (112 ANA-positive, 111 ANA-negative). Baseline demographic data, disease activity (DAS28), and serological markers (RF, anti-CCP) were analyzed. Time to biologic therapy initiation, defined from the date of RA diagnosis to first biologic or targeted synthetic DMARD use, was assessed using Kaplan–Meier survival analysis and Cox proportional hazards regression. Multivariate models adjusted for clinically relevant covariates (age, sex, disease duration, RF, anti-CCP). Within the ANA-positive group, exploratory analyses compared low–moderate (1:80–1:320) and high (>1:320) ANA titers, highlighting potential non-linear effects. Results: Baseline demographic and clinical characteristics were comparable between groups (all p > 0.05). ANA-positive patients more frequently initiated biologic therapy (48.2% vs. 24.3%, p < 0.001) and experienced multiple biologic switches (29.5% vs. 16.2%, p = 0.028). In multivariate analysis, ANA positivity independently predicted earlier biologic therapy initiation (adjusted HR 2.14; 95% CI 1.32–3.46; p = 0.002), whereas RF and anti-CCP status were not significant predictors. Exploratory subgroup analysis revealed the “titer paradox,” whereby high ANA titers (>1:320) were associated with a lower hazard of biologic therapy initiation compared with low–moderate titers (HR 0.24; 95% CI 0.06–0.98; p = 0.048). Conclusions: ANA positivity serves as an independent prognostic marker for earlier biologic therapy initiation in RA, providing incremental information beyond traditional serological markers. The observed non-linear association between ANA titers and treatment escalation underscores the need for cautious interpretation and validation in prospective, mechanistic studies, and highlights the potential value of integrating ANA profiling into personalized treatment strategies. Full article

(This article belongs to the Section Clinical Diagnosis and Prognosis)

► Show Figures

Figure 1

12 pages, 740 KB

Open AccessArticle

Acromegalic Uteropathy: Specific Uterine Ultrasound Findings in Female Patients

by Irina Stanoevich, Aurika Asanova, Svetlana Vorotnikova, Andrey Belov, Ekaterina Grezina, Yulia Fedorova, Ugljesa Stanojevic, Larisa Dzeranova, Ekaterina Pigarova, Galina Melnichenko and Natalya Mokrysheva

Diagnostics 2026, 16(6), 956; https://doi.org/10.3390/diagnostics16060956 - 23 Mar 2026

Abstract

Background/Objectives: Acromegaly is a systemic connective tissue disease driven by chronic growth hormone (GH) and insulin-like growth factor-1 (IGF-1) excess; yet, the female reproductive tract—especially the extracellular matrix (ECM)-rich cervix—has been poorly studied. We aimed to compare uterine and cervical morphology in women [...] Read more.

Background/Objectives: Acromegaly is a systemic connective tissue disease driven by chronic growth hormone (GH) and insulin-like growth factor-1 (IGF-1) excess; yet, the female reproductive tract—especially the extracellular matrix (ECM)-rich cervix—has been poorly studied. We aimed to compare uterine and cervical morphology in women with acromegaly versus healthy controls and a gynecologic disease comparator, testing the hypothesis of selective cervical hypertrophy. Methods: We performed a retrospective case–control study of reproductive-age women who underwent pelvic ultrasound: acromegaly (n = 33), healthy controls (n = 45), and adenomyosis without acromegaly (n = 44). Uterine body measurements were obtained by TAUS/TVUS; cervical biometry was performed transvaginally in all cases. Volumes were estimated using the ellipsoid formula, and a uterus-to-cervix (U:C) volume ratio was calculated. Group differences were analyzed with Mann–Whitney tests and Bonferroni correction. Results: A total of 122 women were included. Uterine body length, width, AP size, and volume did not differ between acromegaly and either comparison group (all p-values non-significant). In contrast, cervical length, width, AP thickness, and volume were significantly higher in acromegaly than in healthy controls, with a corresponding reduction in the U:C volume ratio, indicating disproportionate cervical enlargement. Compared with adenomyosis, women with acromegaly again showed larger cervical width, AP thickness, and volume, together with altered U:C indices, whereas cervical length did not differ, suggesting a pattern not explained by nonspecific pelvic pathology. Conclusions: Women with acromegaly demonstrate a distinct uterine phenotype characterized by selective cervical hypertrophy with preserved uterine corpus size—an ECM-centric “acromegalic uteropathy.” This noninvasive morphometric signature may have diagnostic and procedural relevance and warrants confirmation in prospective studies. Full article

(This article belongs to the Special Issue Diagnosis and Prognosis of Gynecological and Obstetric Diseases)

► Show Figures

Figure 1

14 pages, 990 KB

Open AccessArticle

Endocrine Sequelae of Mild Traumatic Brain Injury in Patients Admitted to the Emergency Department: A 12-Month Study

by Maria Kałas, Mariusz Siemiński and Ewelina Stępniewska

Diagnostics 2026, 16(6), 955; https://doi.org/10.3390/diagnostics16060955 - 23 Mar 2026

Abstract

Background/Objectives: Over the last two decades, there has been a substantial change in the understanding of post-traumatic hypopituitarism (PTHP), which is no longer regarded as a marginal phenomenon. Clinical manifestations of pituitary hormone deficiency are frequently nonspecific, with fatigue and cognitive dysfunction predominating. [...] Read more.

Background/Objectives: Over the last two decades, there has been a substantial change in the understanding of post-traumatic hypopituitarism (PTHP), which is no longer regarded as a marginal phenomenon. Clinical manifestations of pituitary hormone deficiency are frequently nonspecific, with fatigue and cognitive dysfunction predominating. Given that head injuries currently constitute a global burden for healthcare systems, the aim of the present study was to determine whether self-reported post-mild traumatic brain injury (mTBI) symptoms that may indicate hypopituitarism reflect true pituitary insufficiency or are attributable to other hormonal aberrations. The study aimed to assess the relationship between self-reported symptoms of PTHP and hormonal test results following mTBI. Setting: Patients were recruited from a tertiary trauma center Emergency Department (ED) in northern Poland from January 2023 to October 2025. Participants: The participants were adult (18 > y.o.) individuals with mTBI who met the inclusion criteria. Design: This was a prospective cohort study. During their post-head injury admission to the ED, patients had a blood sample taken. The procedure was repeated consecutively after 3, 6 and 12 months. After 6 and 12 months, patients were asked to complete a questionnaire. Methods: Pituitary and thyroid hormones were measured using the chemiluminescence immunoassay method and the heterogenous immunochemiluminescence method. The questionnaire used, Questionnaire for the Assessment of Symptoms of Anterior Pituitary Insufficiency in Patients After Mild Traumatic Brain Injury (mTBI) Hospitalized in the Emergency Department, was designed for the purposes of this study. Results: Self-reported symptoms suggestive of anterior pituitary dysfunction following mTBI were not confirmed by laboratory assessment of pituitary hormones. However, after 6 months, a statistically significant correlation was found between the number of reported symptoms and prolactin levels (ρ = 0.730; p = 0.0013), whereas after 12 months a downward trend in free triiodothyronine (fT3) levels was observed compared with the baseline. Conclusions: Persistent symptoms reported by patients following mTBI at 6 and 12 months, particularly fatigue and impaired concentration, showed statistical associations with prolactin levels at 6 months and lower fT3 levels at 12 months. These findings reflect correlations identified in the statistical analysis and do not support inferences regarding causality or the presence of true PTHP. Full article

(This article belongs to the Special Issue Traumatic Brain Injury and Associated Neurological and Neuropsychiatric Disorders: Diagnosis/Prognosis and Therapeutics)

► Show Figures

Figure 1

12 pages, 1203 KB

Open AccessArticle

Interpretable Machine Learning for Emergency Department Triage: Clinical Insights from 133,198 Patients Using the Korean Triage and Acuity Scale (KTAS)

by MyoungJe Song, Jongsun Kim, Eun-Chul Jang and SoonChan Kwon

Diagnostics 2026, 16(6), 954; https://doi.org/10.3390/diagnostics16060954 - 23 Mar 2026

Abstract

Background/Objectives: Emergency room severity classification (KTAS) is essential for patient safety but has limitations due to its reliance on subjective judgment. Existing machine learning models have not been trusted in clinical settings due to their opaque ‘black box’ nature in decision-making processes. To [...] Read more.

Background/Objectives: Emergency room severity classification (KTAS) is essential for patient safety but has limitations due to its reliance on subjective judgment. Existing machine learning models have not been trusted in clinical settings due to their opaque ‘black box’ nature in decision-making processes. To overcome this, this study aims to develop an explainable machine learning framework that provides a transparent basis for judgment with high accuracy. Method: We retrospectively analyzed 133,198 emergency room visits from 2022 to 2024. We trained Random Forest (RF) and XGBoost models using vital signs and pain scores and applied explainable AI (XAI) techniques to ensure model transparency. Results: Although XGBoost showed the highest predictive performance (94.7% accuracy within a ±1 error margin), we ultimately selected the RF model, which provides a good balance of predictive power (91.6%) and interpretability for clinical use. The results of the XAI analysis confirmed that pain score, age, and systolic blood pressure were the key variables in prediction, strongly aligning with clinical logic. Conclusions: This study demonstrates that explainable AI can provide transparent insights for KTAS prediction beyond the limitations of traditional black-box models. These models may support emergency department triage by improving consistency and assisting clinicians in identifying potentially high-risk patients. However, further external validation is required before routine clinical implementation. Full article

(This article belongs to the Section Machine Learning and Artificial Intelligence in Diagnostics)

► Show Figures

Figure 1

25 pages, 5903 KB

Open AccessCase Report

The Efficiency of Allotransplant in a Case of Acute Biphenotypic Myeloid and B-Lymphoid Leukemia (MPAL Myelo/B NOS) That Presented Concurrently with a Mediastinal Granulocytic Sarcoma Co-Expressing Lymphoid Markers Complicated by Cardiac Tamponade

by Alina Camelia Catana, Erzebeth Lazar Benedek, Ioan Zaharie, Liliana Mocanu, Geanina Mera, Cristina Popa and Lidia-Maria Mondoc

Diagnostics 2026, 16(6), 953; https://doi.org/10.3390/diagnostics16060953 - 23 Mar 2026

Abstract

Background and Clinical Significance: Mixed-phenotype acute leukemia (MPAL) is a rare hematologic malignancy characterized by the co-expression of myeloid and lymphoid markers and is associated with poor prognosis. Myeloid sarcoma (MS), particularly in the mediastinum, is an uncommon extramedullary manifestation and is [...] Read more.

Background and Clinical Significance: Mixed-phenotype acute leukemia (MPAL) is a rare hematologic malignancy characterized by the co-expression of myeloid and lymphoid markers and is associated with poor prognosis. Myeloid sarcoma (MS), particularly in the mediastinum, is an uncommon extramedullary manifestation and is rarely reported in association with MPAL. Case Presentation: We report a rare case of mediastinal MS with biphenotypic features and pericardial extension occurring concurrently with MPAL, highlighting diagnostic challenges, therapeutic strategies, and long-term outcomes. We describe the clinical course, diagnostic workup, treatment, and follow-up of a 21-year-old woman who presented with cardiac tamponade secondary to a mediastinal mass. Histopathology and immunophenotyping established the diagnosis of mediastinal MS associated with MPAL (B/myeloid, NOS). Management included surgical cytoreduction, intensive induction chemotherapy, and consolidation with allogeneic hematopoietic stem cell transplantation (allo-HSCT) from an unrelated donor. Fertility preservation with oocyte retrieval, in vitro fertilization (IVF), and embryo cryopreservation was performed prior to conditioning. A focused literature review of MPAL cases with extramedullary involvement was conducted. The patient achieved complete remission following induction therapy and underwent allo-HSCT. Despite the historically poor prognosis of mediastinal MS and MPAL, she remains in sustained complete remission 13 years after diagnosis. A literature review identified only eight reported cases of MPAL with extramedullary disease, with mediastinal involvement described in a single case and allo-HSCT performed in only two patients. Conclusions: This case illustrates a rare presentation of MPAL with mediastinal myeloid sarcoma and cardiac tamponade, demonstrating that aggressive multimodal therapy including allo-HSCT may achieve durable remission even in high-risk presentations. Early multidisciplinary management and consideration of fertility preservation are essential in young patients. Full article

(This article belongs to the Special Issue Diagnosis and Management of Hematologic Malignancies)

► Show Figures

Figure 1

13 pages, 747 KB

Open AccessArticle

Pre-Operative Sonographic Assessment of Ovarian Location and Mobility Predicts Intra-Operative Ovarian Resectability During Vaginal Hysterectomy: A Diagnostic Accuracy Study

by Iakovos Theodoulidis, Nikolaos Roussos, Menelaos Zafrakas, Christos Anthoulakis, Pantelis Trompoukis, Grigorios F. Grimbizis and Themistoklis Mikos

Diagnostics 2026, 16(6), 952; https://doi.org/10.3390/diagnostics16060952 - 23 Mar 2026

Abstract

Background/Objectives: This study investigates the predictive role of pre-operative sonographic assessment of ovarian mobility in determining intra-operative ovarian resectability among patients undergoing vaginal hysterectomy for pelvic organ prolapse. Methods: This prospective study was conducted in a tertiary academic urogynecology center. Women [...] Read more.

Background/Objectives: This study investigates the predictive role of pre-operative sonographic assessment of ovarian mobility in determining intra-operative ovarian resectability among patients undergoing vaginal hysterectomy for pelvic organ prolapse. Methods: This prospective study was conducted in a tertiary academic urogynecology center. Women with pelvic organ prolapse scheduled for vaginal hysterectomy were consecutively recruited after providing informed consent. Pre-operatively, all patients had a detailed history, pelvic examination (POP-Q), and pelvic floor ultrasound (including assessment of the mobility of both ovaries and sonographic determination of ovarian descent in relation to the pelvic ischial spines). Patients were planned for vaginal hysterectomy, anterior and posterior colporrhaphy, McCall culdoplasty, and bilateral salpingo-oophorectomy (SO), where feasible. During surgery, the location and mobility of the ovaries, as well as the presence of peri-ovarian adhesions, were recorded. Pair-to-pair comparisons between sonographic and clinical findings were performed. Results: From February 2023 to January 2024, 50 Caucasian adult women underwent reconstructive vaginal surgery for prolapse. Thirty-five patients underwent concomitant bilateral SO via vaginal route, seven underwent unilateral SO, and three under went salpingectomy only. ROC analysis indicated that pre-operative ultrasound assessment of ovarian mobility predicts: (1) intra-operative ovarian mobility (sensitivity 95.6%, specificity 77.8%); (2) the presence of peri-ovarian adhesions (sensitivity 46.1%, specificity 94.2%); and (3) resectability, i.e., the ability to perform SO via the vaginal route (sensitivity 96.4%, specificity 50.0%). The absence of ovarian mobility was not associated with an increased risk of intra-operative and post-operative complications. Conclusions: Pre-operative sonographic assessment of ovarian location and mobility can predict ovarian location and resectability during vaginal surgery with high diagnostic accuracy. Full article

(This article belongs to the Special Issue Diagnostic Advances in Obstetrics and Gynecology, Breast Disease and Women’s Health)

► Show Figures

Figure 1

19 pages, 3121 KB

Open AccessSystematic Review

Comparative Diagnostic Performance of TST and IGRAs in the Diagnosis of Latent Tuberculosis Infection: A Systematic Review and Diagnostic Meta-Analysis

by Shyamkumar Sriram, Tareq Abualfaraj, Manal Ali Alsharif, Marwa Zalat, Saad Madani Alawfi, Hammad Ali Fadlalmola and Muayad Albadrani

Diagnostics 2026, 16(6), 951; https://doi.org/10.3390/diagnostics16060951 - 23 Mar 2026

Abstract

Background: Patients with latent tuberculosis infection are mainly asymptomatic, but they still carry a notable risk of developing active TB, particularly when the host becomes immunosuppressed. Hence, appropriate diagnosis and management for LTBI are essential. Tuberculin skin test (TST) and interferon-gamma release assays [...] Read more.

Background: Patients with latent tuberculosis infection are mainly asymptomatic, but they still carry a notable risk of developing active TB, particularly when the host becomes immunosuppressed. Hence, appropriate diagnosis and management for LTBI are essential. Tuberculin skin test (TST) and interferon-gamma release assays (IGRAs) are among the most commonly utilized methods for detecting LTBI. Until now, no agreement has been established regarding the most effective diagnostic test, either TST or IGRA, so our study aims to evaluate the diagnostic utility of TST versus IGRA in detecting LTBI. Methods: An extensive literature search was executed in several databases from inception till June 2024. We included all the available studies that compared TST versus IGRA concurrently applied to the same study participants, utilizing one of the following proxy reference standards: previous contact with a tuberculosis patient, tuberculosis history, chest x-ray suggestive of tuberculosis, or a combination of them. The sensitivity (SN) and specificity (SP) were imputed with their 95% confidence interval (CI). A bivariate random-effects model within the OpenMeta-Analyst software was utilized for data analysis. Results: We included 39 studies, and our primary analysis regarding LTBI revealed that TST has an SN of 0.320 (95% CI [0.254–0.393]) and an SP of 0.808 (95% CI [0.752–0.854]). Nevertheless, the IGRA exhibited a higher SN estimated at 0.362 (95% CI [0.295–0.434]) and a lower SP estimated at 0.758 (95% CI [0.700–0.808]). Regarding the adult population, TST consistently showed a lower SN and a higher SP relative to IGRA. However, within the pediatric population, TST showed higher SN and lower SP when compared to IGRA. Furthermore, TST also showed a lower SN and a higher SP within hemodialysis and organ transplant patients than IGRA. Conclusions: Our diagnostic test meta-analysis revealed that TST was associated with a lower SN and a higher SP than IGRA. Clinicians should interpret these findings with caution, considering the substantial heterogeneity observed across the included studies, the reliance on proxy reference standards, the potential influence of BCG vaccination status, and the considerable overlap in confidence intervals between TST and IGRA estimates across most analyses. Full article

(This article belongs to the Section Diagnostic Microbiology and Infectious Disease)

► Show Figures

Figure 1

16 pages, 764 KB

Open AccessArticle

Integrating Tumor Biology and Host Factors in mCRPC: The Prognostic Value of ‘Time to Castration Resistance’, Systemic Inflammation, and Comorbidity Burden in Patients Treated with Enzalutamide

by Seda Sali, Arife Ulaş, Sibel Oyucu Orhan, Sevgi Topçu, Muharrem Koçar, Mürsel Sali, Birol Ocak, Adem Deligönül, Türkkan Evrensel and Erdem Çubukçu

Diagnostics 2026, 16(6), 950; https://doi.org/10.3390/diagnostics16060950 - 23 Mar 2026

Abstract

Background: Outcomes with enzalutamide in metastatic castration-resistant prostate cancer (mCRPC) are influenced by tumor burden, disease kinetics, and host factors. We evaluated the relative prognostic impact of metastatic pattern, laboratory markers, and prostate-specific antigen (PSA) dynamics in a real-world cohort. Methods: We retrospectively [...] Read more.

Background: Outcomes with enzalutamide in metastatic castration-resistant prostate cancer (mCRPC) are influenced by tumor burden, disease kinetics, and host factors. We evaluated the relative prognostic impact of metastatic pattern, laboratory markers, and prostate-specific antigen (PSA) dynamics in a real-world cohort. Methods: We retrospectively analyzed 72 patients with mCRPC treated with enzalutamide. Progression-Free Survival (PFS) and Overall Survival (OS) were estimated using the Kaplan–Meier method. Multivariate Cox proportional hazards models were utilized to identify independent predictors of survival, incorporating clinical variables (visceral metastases, bone tumor burden), kinetic parameters (Time to Castration Resistance [TTCR], Time to PSA Nadir [TTN]), and host factors (Charlson Comorbidity Index [CCI], Eastern Cooperative Oncology Group Performance Status (ECOG PS), Systemic Immune-Inflammation Index [SII], HALP score). Results: Visceral metastasis was a dominant predictor of poor outcomes, increasing the risk of death by 4.0-fold (HR: 4.05; 95% CI: 1.84–8.89; p < 0.001). A high skeletal tumor burden (≥5 bone lesions) was identified as a critical threshold, associated with a 5.5-fold increase in mortality risk (HR: 5.53; p < 0.001). Delays in initiating enzalutamide significantly compromised survival, with each 1-month delay increasing the risk of death by 7.3% (HR: 1.07; p = 0.003). While early PSA decline (≥50% at 3 months) did not independently predict OS, a prolonged TTN (>12 months) was associated with superior survival. Notably, host-related factors, including age, CCI, and ECOG PS, were not found to be significantly associated with survival outcomes in this specific dataset. Conclusions: Our preliminary findings suggest that survival in real-world mCRPC patients treated with enzalutamide may be influenced predominantly by intrinsic tumor biology—specifically anatomical extent and resistance kinetics—rather than host frailty or comorbidity burden. However, given the retrospective and single-center nature of this study, these findings should be considered hypothesis-generating and require validation in larger, multi-center cohorts. Host-related variables (including age and CCI) were evaluated but were not retained as independent predictors in the final multivariable model. Early initiation of therapy and monitoring of kinetic markers like TTN and TTCR offer superior prognostic stratification compared to static baseline characteristics. Full article

(This article belongs to the Special Issue Prostate Cancer: Innovations in Diagnosis and Risk Stratification)

► Show Figures

Figure 1

22 pages, 848 KB

Open AccessArticle

Digital Specimen Tracking- and ISO 15189-Oriented Risk Management in Anatomic Pathology: A Qualitative Study of Expert Perspectives in Western Austria

by Pius Sommeregger, Natalie Pallua, Bettina Zelger, Riem Kahlil and Johannes Dominikus Pallua

Diagnostics 2026, 16(6), 949; https://doi.org/10.3390/diagnostics16060949 - 23 Mar 2026

Abstract

Background: Breakpoints in the pre-examination processes and at organizational interfaces are a significant source of failures in specimen identification and tracking in anatomic pathology. While ISO 15189 emphasizes end-to-end traceability and risk-based quality management, implementing these principles in complex, multi-actor specimen pathways [...] Read more.

Background: Breakpoints in the pre-examination processes and at organizational interfaces are a significant source of failures in specimen identification and tracking in anatomic pathology. While ISO 15189 emphasizes end-to-end traceability and risk-based quality management, implementing these principles in complex, multi-actor specimen pathways remains challenging. This study explores expert perspectives on specimen process chains, tracking mechanisms, and ISO 15189-oriented quality and risk management in pathology. Methods: We conducted 10 semi-structured expert interviews across three settings. Interviews were audio-recorded, transcribed, pseudonymized, and analyzed using structured qualitative content analysis (Mayring) supported by MAXQDA. A deductive category system derived from the theoretical framework and interview guide comprised six main categories and twelve subcategories. Results: Across 512 coded text segments, participants identified several factors as critical for effective implementation, including: (i) interface management along the specimen pathway, with recurrent vulnerabilities at handovers between operating theater/ward/transport and accessioning; (ii) the central role of barcode-based identification and the need for closed-loop traceability; (iii) the importance of measurable quality indicators and incident learning systems to operationalize risk management; (iv) persistent paper–digital handoffs and heterogeneous IT landscapes that undermine data integrity; (v) the need for clearly assigned responsibilities, training, and SOP governance; and (vi) implementation barriers including resources, change management, and vendor integration, alongside practical enablers such as incremental roll-out and cross-professional governance. Conclusions: Experts converge on a pragmatic ISO 15189-aligned roadmap: prioritize interface risks, standardize identifiers and handover rules, define a minimal KPI set for tracking and misidentification events, and reduce paper–digital handoffs by interoperable IT. Future work should quantify baseline error rates and evaluate the impact of digital tracking interventions on patient safety and turnaround times. Full article

(This article belongs to the Section Pathology and Molecular Diagnostics)

► Show Figures

Figure 1

23 pages, 4643 KB

Open AccessArticle

Assessment of Early Breast Cancer Response to Chemotherapy with Ultrasound Radiomics

by Swapnil Dolui, Basak Dogan, Corinne Wessner, Jessica Porembka, Priscilla Machado, Bersu Ozcan, Nisha Unni, Maysa Abu Khalaf, Flemming Forsberg, Kibo Nam and Kenneth Hoyt

Diagnostics 2026, 16(6), 948; https://doi.org/10.3390/diagnostics16060948 - 23 Mar 2026

Abstract

Objective: This prospective study investigated the use of H-scan ultrasound (US) imaging as a novel component of a multiparametric radiomic analysis framework for characterizing human breast cancer response to neoadjuvant chemotherapy (NAC) before and early after treatment initiation. Methods: Thirty breast [...] Read more.

Objective: This prospective study investigated the use of H-scan ultrasound (US) imaging as a novel component of a multiparametric radiomic analysis framework for characterizing human breast cancer response to neoadjuvant chemotherapy (NAC) before and early after treatment initiation. Methods: Thirty breast cancer patients scheduled for NAC were scanned using a clinical US system (Logiq E9, GE HealthCare) equipped with a 9L-D linear array transducer. Radiofrequency (RF) data was obtained at baseline (pre-NAC) and after 10% and 30% of the complete dose of chemotherapy. The RF data was analyzed by a bank of 256 frequency-shifted bandpass filters to form H-scan US frequency images. Grayscale texture features were extracted from both B-scan and H-scan US images. In addition, US attenuation coefficient and speckle statistics based on the Nakagami and Burr distributions were estimated from the RF data. Data classification of tumor and peri-tumoral regions was performed using a novel three-dimensional (3D) score map based on support vector machine (SVM) modeling. Unlike conventional classifiers that report only a single prediction score, a 3D score map provides a visual representation of the classifier decision space, enabling interpretation of class separation and treatment-induced shifts in multiparametric US measurements. Results: The dataset was split into 10 disjoint partitions (90% training, 10% testing) to compute area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and accuracy measures. Actual patient response to NAC was assessed at surgery and categorized as either pathologic complete response (pCR) or non-pCR. Multiparametric US and data classification results at pre-NAC found AUC values of 0.78 after using only tumor information (p < 0.01), which increased to 0.81 with inclusion of peri-tumoral information (p < 0.01). Significant differences in multiparametric US measures from both cancer response types was found after integration of patient data collected at 10% completion of the NAC regimen (i.e., first NAC cycle), yielding an improved AUC of 0.86 (p < 0.001). Conclusions: Multiparametric US imaging with radiomic features from both the tumor and peri-tumoral regions is a promising noninvasive approach for monitoring early breast cancer response to NAC. Full article

(This article belongs to the Section Medical Imaging and Theranostics)

► Show Figures

Figure 1

12 pages, 942 KB

Open AccessArticle

Cephalometric Assessment of Airway-Related Hyoid Position and Velar Morphology Across Skeletal Malocclusions: A Cross-Sectional Study

by Gizem Yazdan Özen, Ali Kağan Özen and Nebiha Hilal Bilge

Diagnostics 2026, 16(6), 947; https://doi.org/10.3390/diagnostics16060947 - 23 Mar 2026

Abstract

Background: The anatomical position of the hyoid bone and the morphological characteristics of the soft palate play a key role in upper airway patency, craniofacial balance, and the coordination of functional structures. These features may vary depending on skeletal pattern and gender. This [...] Read more.

Background: The anatomical position of the hyoid bone and the morphological characteristics of the soft palate play a key role in upper airway patency, craniofacial balance, and the coordination of functional structures. These features may vary depending on skeletal pattern and gender. This study aimed to evaluate the relationship between hyoid bone position, soft palate morphology, skeletal classification, and gender using lateral cephalograms. Methods: A total of 120 individuals (60 females and 60 males) were classified as Skeletal Class I, II, or III based on the ANB (A Point–Nasion–B Point) angle. Measurements reflecting hyoid position and pharyngeal airway width were analyzed, including C3–H (distance from the third cervical vertebra to the hyoid bone), C3–RGn (distance from the third cervical vertebra to retrognathion), H–RGn (distance from the hyoid bone to retrognathion), PNS–UPW (distance from the posterior nasal spine to the upper pharyngeal wall), and U–MPW (distance from the uvula to the middle pharyngeal wall). Soft palate types were classified according to the You classification. Statistical analyses included ANOVA (analysis of variance), the Kruskal–Wallis test, the independent samples t-test, the Mann–Whitney U test, and the chi-square test. Results: Significant differences in C3–RGn, H–RGn, and U–MPW were observed between Skeletal Classes I–III and Classes II–III (p < 0.05). In contrast, C3–H and PNS–UPW did not differ significantly among skeletal classes. Soft palate types showed no significant association with skeletal classification or gender. Gender-based comparisons revealed significant differences in C3–H, C3–RGn, H–RGn, and PNS–UPW (p < 0.05). Conclusions: Mandibular-related hyoid measurements and the U–MPW parameter were associated with skeletal pattern, whereas C3–H and PNS–UPW remained relatively stable. Soft palate morphology was not significantly influenced by skeletal class or gender. These findings suggest that the hyoid–tongue–soft palate complex should be evaluated in conjunction with mandibular position during orthodontic diagnosis and treatment planning. Full article

(This article belongs to the Section Clinical Diagnosis and Prognosis)

► Show Figures

Figure 1

26 pages, 5481 KB

Open AccessReview

Intrapartum Ultrasound in Vacuum Operative Delivery: A Comprehensive Review and Proposal of the Novel Ultrasound Flexion Point Method

by Antonio Malvasi, Giorgio Maria Baldini, Tommaso Difonzo, Marco Cerbone, Iris Cara, Marianna Demarco, Ilenia Mappa, Giuseppe Rizzo, Antonella Vimercati, Miriam Dellino, Andrea Tinelli, Edoardo Di Naro and Lorenzo E. Malgieri

Diagnostics 2026, 16(6), 946; https://doi.org/10.3390/diagnostics16060946 - 23 Mar 2026

Abstract

Operative vaginal delivery (OVD) via vacuum extraction is a fundamental component of modern obstetric management, yet it carries specific risks of failure and maternal–fetal complications, such as cup detachment, cephalohematoma, and intracranial hemorrhage. The success and safety of the procedure rely heavily on [...] Read more.

Operative vaginal delivery (OVD) via vacuum extraction is a fundamental component of modern obstetric management, yet it carries specific risks of failure and maternal–fetal complications, such as cup detachment, cephalohematoma, and intracranial hemorrhage. The success and safety of the procedure rely heavily on the correct application of the vacuum cup over the “flexion point” of the fetal head. Traditional identification of this landmark via digital examination is often hindered by caput succedaneum and cranial molding, leading to high rates of diagnostic error, particularly in dystocic labor, due to fetal head malpositions and malpresentation. Intrapartum ultrasound (ITU) has demonstrated superior accuracy compared to clinical examination in assessing fetal head position and station and internal rotation. This expert commentary and technical proposal analyzes the current literature regarding vacuum extraction application and failures, focusing on the predictive value of ITU parameters (e.g., Angle of Progression, Midline Angle, Head-Symphysis Distance) and the impact of ITU on cup placement and delivery outcomes. Furthermore, we propose a novel technique: the “Ultrasound Flexion Point” (UFP). This method utilizes translabial ultrasound to identify the specific intersection of the fetal midline and the biparietal diameter as an objective sonographic proxy for the classical flexion point. By providing spatial orientation guidance immediately before the procedure, this technique aims to guide the operator in aligning the cup’s notch with the sonographically identified target zone, using the midline angle as orientation reference, thereby potentially minimizing paramedian or deflexing applications and reducing the incidence of vacuum detachment and associated neonatal trauma. This expert commentary and technical proposal synthesizes current evidence and proposes a protocol requiring prospective validation through randomized controlled trials. Full article

(This article belongs to the Special Issue Advances in Ultrasound Diagnosis in Maternal Fetal Medicine Practice)

► Show Figures

Figure 1

17 pages, 3545 KB

Open AccessArticle

A Radiomics–Clinical Nomogram for Pre-Treatment Prediction of Neoadjuvant Chemotherapy Response in Locally Advanced Gastric Cancer

by Qianzheng Zhou, Jun Xu, Qiong Li, Fengyuan Li and Hao Xu

Diagnostics 2026, 16(6), 945; https://doi.org/10.3390/diagnostics16060945 - 23 Mar 2026

Abstract

Objective: To develop and evaluate a nomogram integrating radiomic features from contrast-enhanced CT with clinical variables for pre-treatment predictions of the response to neoadjuvant therapy (NAT) in locally advanced gastric cancer (LAGC). Methods: In this retrospective multicenter study, 183 LAGC patients from the [...] Read more.

Objective: To develop and evaluate a nomogram integrating radiomic features from contrast-enhanced CT with clinical variables for pre-treatment predictions of the response to neoadjuvant therapy (NAT) in locally advanced gastric cancer (LAGC). Methods: In this retrospective multicenter study, 183 LAGC patients from the First Affiliated Hospital of Nanjing Medical University (2014–2023) were included. Radiomic features were extracted from manually delineated pre-treatment CT regions of interest. A machine learning-based predictive model combining radiomic scores and clinical data was constructed. Model performance was assessed using receiver operating characteristic (ROC) analysis, calibration curves, and decision curve analysis (DCA). Results: Multivariate analysis identified the radiomic score, preoperative N stage, and neoadjuvant regimen as independent predictors of NAT responses (all p < 0.05). The integrated nomogram achieved an area under the ROC curve of 0.807 and showed a moderate net benefit in DCA compared with the radiomics-only model. Conclusions: The radiomics–clinical nomogram demonstrates moderate predictive performance for pre-treatment stratification of NAT responses in LAGC. These findings are exploratory and hypothesis-generating, and further validation in independent cohorts is required before clinical application. Full article

(This article belongs to the Special Issue Imaging Research on Gastrointestinal Disorders: Second Edition)

► Show Figures

Figure 1

15 pages, 1686 KB

Open AccessArticle

Establishment and Temporal Validation of Next-Generation Reference Intervals for Routine Hematological Parameters Using Large-Scale Data

by Chaochao Ma, Lihua Guan, Qian Chen, Rongrong Cheng, Wei Wu and Ling Qiu

Diagnostics 2026, 16(6), 944; https://doi.org/10.3390/diagnostics16060944 - 23 Mar 2026

Abstract

Background: Conventional reference intervals (RIs) are typically expressed as fixed limits and may not adequately reflect continuous biological variation across age and sex. Next-generation reference intervals (NGRIs) allow dynamic modeling of laboratory parameters across the lifespan. This study aimed to establish age- [...] Read more.

Background: Conventional reference intervals (RIs) are typically expressed as fixed limits and may not adequately reflect continuous biological variation across age and sex. Next-generation reference intervals (NGRIs) allow dynamic modeling of laboratory parameters across the lifespan. This study aimed to establish age- and sex-specific NGRIs for routine hematological parameters using large-scale health examination data and to evaluate their temporal stability. Methods: Health examination records were linked with laboratory data, and a relatively healthy reference population was defined based on age (18–80 years), normal body mass index, normal blood pressure, and absence of documented disease history. NGRIs were constructed using generalized additive models for location, scale, and shape (GAMLSS) with the Box–Cox Cole and Green distribution. Age-dependent percentile curves (2.5th–97.5th) were generated using bootstrap resampling (100 iterations). Temporal external validation was conducted in five independent annual cohorts (2019–2023). Results: Age- and sex-dependent distributional patterns were observed across multiple hematological parameters, particularly RBC, HGB, and HCT. Continuous percentile curves demonstrated gradual age-related trends, with more pronounced changes in females after midlife. In temporal validation cohorts, the proportion of individuals classified outside the reference intervals remained consistently below 10% across years and sexes, indicating stable performance. Conclusions: Using large-scale real-world health examination data and a flexible distributional modeling framework, we established stable age-continuous next-generation reference intervals for routine hematological parameters. The proposed approach provides a reproducible strategy for modernizing laboratory reference interval construction and supports broader implementation in population-based laboratory medicine. Full article

(This article belongs to the Special Issue Advancing Blood-Based Diagnostics: Innovations, Challenges and Clinical Impact)

► Show Figures

Figure 1

21 pages, 3822 KB

Open AccessArticle

Uncertainty-Aware Framework for CT Radiation Dose Optimization in the Active Surveillance of Small Renal Masses: Clinical and Radiological Considerations

by M. A. Elsabagh, Amira Samy Talaat, Dalia Elwi, Shaimaa M. Hassan, Sameer Alqassimi and Esraa Hassan

Diagnostics 2026, 16(6), 943; https://doi.org/10.3390/diagnostics16060943 - 23 Mar 2026

Abstract

Background: Active surveillance of small renal masses is challenged by cumulative radiation exposure from repeated CT imaging, raising long-term health concerns. Low-dose CT protocols offer a strategy to mitigate this risk but are limited by uncertainty regarding measurement accuracy and potential effects on [...] Read more.

Background: Active surveillance of small renal masses is challenged by cumulative radiation exposure from repeated CT imaging, raising long-term health concerns. Low-dose CT protocols offer a strategy to mitigate this risk but are limited by uncertainty regarding measurement accuracy and potential effects on clinical decision-making. Methods: We propose an uncertainty-aware analytical framework using a multi-observer dataset of 40 paired CT cases (low-dose vs. standard-dose). The methodology combines statistical agreement assessment (concordance correlation coefficient, intraclass correlation coefficient), multi-algorithm machine learning prediction (linear regression, random forest, gradient boosting, and SVR), and integrated uncertainty quantification to evaluate equivalence across imaging protocols. Results: Comparative analysis demonstrates near-perfect concordance between protocols (concordance correlation coefficient = 0.9930). Linear regression achieved the highest predictive performance (R² = 0.9933, MAE = 0.4239 mm, MAPE = 2.07%), outperforming more complex ensemble models, highlighting that interpretable models can achieve superior accuracy without compromising reliability. Conclusions: Clinically, the framework supports the safe adoption of low-dose CT for longitudinal tumor assessment, preserving measurement fidelity and diagnostic confidence essential for timely intervention or continued surveillance. Radiologically, it ensures robust lesion characterization across protocols while minimizing cumulative radiation exposure, particularly in younger patients. By integrating uncertainty quantification, this approach enhances transparency, informs clinical decision-making, and facilitates personalized, evidence-based surveillance strategies, promoting safer, dose-optimized imaging in the management of small renal masses. Full article

(This article belongs to the Section Medical Imaging and Theranostics)

► Show Figures

Figure 1

15 pages, 339 KB

Open AccessArticle

Short-Term Heart Rate Variability Dynamics and Mortality Risk After Acute Coronary Syndrome

by Nikola Marković, Maša Petrović, Silvana Babić, Milovan Bojić and Branislav Milovanović

Diagnostics 2026, 16(6), 942; https://doi.org/10.3390/diagnostics16060942 - 23 Mar 2026

Abstract

Background/Objectives: Heart rate variability (HRV) is a non-invasive marker of autonomic nervous system function with established prognostic value after acute coronary syndrome (ACS). The clinical relevance of temporal changes in short-term HRV remains insufficiently defined. This study evaluated short-term HRV dynamics and their [...] Read more.

Background/Objectives: Heart rate variability (HRV) is a non-invasive marker of autonomic nervous system function with established prognostic value after acute coronary syndrome (ACS). The clinical relevance of temporal changes in short-term HRV remains insufficiently defined. This study evaluated short-term HRV dynamics and their association with mortality after ACS. Methods: This retrospective–prospective study included 230 patients with acute myocardial infarction. Five-minute resting ECG recordings were obtained on day 1 and day 21. Time- and frequency-domain HRV parameters were analyzed, and delta values were calculated. The primary endpoint was overall mortality. Survival was assessed using Kaplan–Meier analysis and Cox regression. Results: Patients who died during follow-up had lower HRV values on day 21 and more pronounced declines in selected parameters. In multivariable analysis, decreased ΔLF and shorter RR intervals independently predicted overall mortality. Conclusions: Short-term HRV provides a practical bedside assessment of autonomic function after ACS. Unfavorable temporal changes likely reflect persistent autonomic imbalance and may offer additional prognostic insight. Larger contemporary studies are needed to confirm these findings. Full article

(This article belongs to the Section Medical Imaging and Theranostics)

► Show Figures

Figure 1

6 pages, 674 KB

Open AccessInteresting Images

Brachial Artery Pseudoaneurysm as a Complication of Osteochondral Exostosis of the Humerus in Computed Tomography Angiography Images

by Paweł Gać, Michał Wesołowski, Kamil Biedka and Rafał Poręba

Diagnostics 2026, 16(6), 941; https://doi.org/10.3390/diagnostics16060941 - 22 Mar 2026

Abstract

We present computed tomography angiography images of a rare pseudoaneurysm of the left brachial artery, a complication of idiopathic injury to the artery caused by an osteochondral exostosis of the left humerus. A 22-year-old Caucasian man with no significant medical history was admitted [...] Read more.

We present computed tomography angiography images of a rare pseudoaneurysm of the left brachial artery, a complication of idiopathic injury to the artery caused by an osteochondral exostosis of the left humerus. A 22-year-old Caucasian man with no significant medical history was admitted to the emergency department due to sudden, intense pain in his left arm, numbness, and pallor of his left forearm and hand. The patient’s consulting vascular surgeon referred him to the computed tomography (CT) laboratory for a computed tomography angiography (CTA) of the arteries of his left upper limb. In the CTA examination, at the level of the proximal segment of the left brachial artery, an excess of contrast was visualized, measuring up to approximately 1.5 × 1.2 cm in cross-sections and up to approximately 0.7 cm in the craniocaudal dimension. The CTA image was suggestive of a pseudoaneurysm of the left brachial artery. Laterally, the pseudoaneurysm was adjacent to the apex of the imaged osteochondral exostosis on the medial surface of the proximal shaft of the left humerus. A surgical procedure was performed to repair the pseudoaneurysm of the left brachial artery, including removal of the bony exostosis of the left humerus. In summary, relatively common, benign bone lesions can occasionally result in serious vascular complications. CTA is the gold standard for diagnosing these complications. Full article

(This article belongs to the Section Medical Imaging and Theranostics)

► Show Figures

Figure 1

6 pages, 2697 KB

Open AccessInteresting Images

The Diagnostic Challenge of Rapunzel Syndrome: Multimodal Imaging Findings in a Child

by Chih-Hao Wang and Shu-Chao Weng

Diagnostics 2026, 16(6), 940; https://doi.org/10.3390/diagnostics16060940 - 22 Mar 2026

Abstract

We report the case of a school-aged patient with attention-deficit/hyperactivity disorder who presented with a palpable epigastric mass. The initial abdominal ultrasonography indicated the presence of a heterogeneous space-occupying lesion in the upper abdomen. Subsequent computed tomography revealed a large intragastric mass with [...] Read more.

We report the case of a school-aged patient with attention-deficit/hyperactivity disorder who presented with a palpable epigastric mass. The initial abdominal ultrasonography indicated the presence of a heterogeneous space-occupying lesion in the upper abdomen. Subsequent computed tomography revealed a large intragastric mass with a mottled air-containing density, an imaging feature characteristic of a bezoar. Esophagogastroduodenoscopy confirmed a massive trichobezoar extending beyond the pylorus into the duodenum, consistent with Rapunzel syndrome. Although the endoscopic removal proved unsuccessful, a subsequent surgical extraction via laparotomy yielded a 22 cm trichobezoar. Further history revealed prior hair-picking behavior approximately one year earlier, with a localized bald patch noted by her parents. This case highlights the characteristic multimodal imaging findings of trichobezoars and serves to emphasize the diagnostic challenge posed by a limited clinical history in children with psychiatric comorbidities presenting with abdominal masses. Full article

(This article belongs to the Section Medical Imaging and Theranostics)

► Show Figures

Figure 1

17 pages, 900 KB

Open AccessArticle

Association of Serum Glucose/Potassium Ratio with Injury Severity and Transfusion Requirements in Traumatic Pelvic Fractures: A Retrospective Cohort Study

by Abdullah Alper Sahin, Yunus Emre Özbilen and Çağrı Akalın

Diagnostics 2026, 16(6), 939; https://doi.org/10.3390/diagnostics16060939 - 22 Mar 2026

Abstract

Background: We evaluated the association between admission serum glucose-to-potassium ratio (GPR) and injury severity as well as early transfusion requirements in patients with traumatic pelvic fractures. Methods: This single-center, retrospective cohort study included 84 adult patients with isolated or predominantly pelvic fractures admitted [...] Read more.

Background: We evaluated the association between admission serum glucose-to-potassium ratio (GPR) and injury severity as well as early transfusion requirements in patients with traumatic pelvic fractures. Methods: This single-center, retrospective cohort study included 84 adult patients with isolated or predominantly pelvic fractures admitted between January 2020 and December 2024. Patients with concomitant non-pelvic skeletal fractures were excluded to isolate the metabolic response attributable to pelvic injury. GPR was calculated from admission serum glucose and potassium levels. Higher transfusion requirement (HT) was defined as ≥4 units of packed red blood cells within 24 h. Receiver operating characteristic (ROC) analysis identified the optimal GPR cut-off using the Youden index. Internal validation was performed using bootstrap resampling (1000 iterations), and model calibration was assessed with the Hosmer–Lemeshow test. The incremental discriminatory value of GPR beyond the Injury Severity Score (ISS) was evaluated by comparing AUC values using the DeLong test, and reclassification metrics including the category-free net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were calculated. Sensitivity analyses were conducted using alternative transfusion thresholds (≥6 and ≥10 units). Results: The optimal GPR cut-off was 34 (area under the curve (AUC) = 0.730; 95% CI: 0.593–0.853; sensitivity 78.8%; specificity 59.0%). Patients with GPR ≥ 34 (n = 43) had significantly higher ISS values (median 25 [IQR: 16–34] vs. 9 [5–17]; p < 0.001), greater transfusion volumes (median 3 [0–6] vs. 0 [0–1] units; p < 0.001), and longer intensive care unit (ICU) stays (3 (0–6) vs. 0 (0–1) days; p < 0.001). In univariable logistic regression, GPR was significantly associated with HT (OR = 1.059 per unit increase; 95% CI: 1.015–1.104; p = 0.008); however, significance was not retained in the multivariable model after adjustment for ISS (p = 0.194). ISS remained the sole independent predictor (OR = 1.128; p < 0.001). The combined ISS + GPR model yielded an AUC of 0.857, representing a modest increment over ISS alone (AUC = 0.849; ΔAUC = 0.009; DeLong p = 0.566). Bootstrap-corrected AUCs confirmed minimal optimism (GPR alone: 0.726; ISS + GPR: 0.847). The Hosmer–Lemeshow test indicated adequate calibration for all models (p > 0.05). The category-free NRI was 0.627 (p = 0.009), whereas the IDI did not reach significance (0.017; p = 0.290). Sensitivity analysis at the ≥6-unit threshold yielded consistent results (GPR AUC = 0.709). Conclusions: Admission GPR is significantly associated with injury severity, hemorrhagic burden, and transfusion requirements in patients with traumatic pelvic fractures. Although GPR does not independently predict transfusion needs beyond ISS, it yields significant reclassification improvement and may serve as a practical, rapidly obtainable adjunct for early risk stratification in the acute trauma setting. Level of Evidence: III (retrospective prognostic study). Full article

(This article belongs to the Section Clinical Diagnosis and Prognosis)

► Show Figures

Graphical abstract

Journal Description

Diagnostics

Latest Articles

Journal Menu

Journal Browser

Highly Accessed Articles

Latest Books

E-Mail Alert

News

Topics

Conferences

Special Issues

Topical Collections

Further Information

Guidelines

MDPI Initiatives

Follow MDPI