Diagnostics

17 pages, 6008 KB

Open AccessCase Report

Novel Sonoguided Digital Palpation and Hydrodissection for Sural Nerve Dysfunction Mimicking Achilles Tendinopathy in a Psoriasis Patient

by Yonghyun Yoon, King Hei Stanley Lam, Howon Lee, Chanwool Park, Seungbeom Kim, Minjae Lee, Jaeyoung Lee, Jihyo Hwang, Hyemi Yu, Jonghyeok Lee, Daniel Chiung-Jui Su, Teinny Suryadi, Anwar Suhaimi and Kenneth Dean Reeves

Diagnostics 2025, 15(21), 2706; https://doi.org/10.3390/diagnostics15212706 (registering DOI) - 25 Oct 2025

Abstract

Background and Clinical Significance: Psoriasis, a chronic immune-mediated inflammatory disease, can affect musculoskeletal structures, including the Achilles tendon. Achilles pain in psoriasis patients may arise from tendinitis or neuropathic pain due to peripheral nerve dysfunction, such as sural nerve (SN) involvement, a condition [...] Read more.

Background and Clinical Significance: Psoriasis, a chronic immune-mediated inflammatory disease, can affect musculoskeletal structures, including the Achilles tendon. Achilles pain in psoriasis patients may arise from tendinitis or neuropathic pain due to peripheral nerve dysfunction, such as sural nerve (SN) involvement, a condition frequently misdiagnosed due to limitations in conventional diagnostics. Fascial tissues are critical in nerve compression syndromes. This case explores the application of a novel quantitative Sonoguide Digital Palpation (SDP) protocol and ultrasound (US)-guided hydrodissection (HD) for SN dysfunction mimicking Achilles tendinopathy in a psoriasis patient. Case Presentation: A 41-year-old male with psoriasis presented with acute onset of right heel stiffness and paresthesia. Physical examination, radiographs, and ultrasound were performed. SDP, employing a validated four-criterion diagnostic framework (including fascial mobility quantification and concordant pain provocation), identified crural fascia restriction affecting SN and reproduced patient’s concordant Achilles pain. High-resolution ultrasonography provided key morphological evidence, revealing a 2.6-fold enlargement of the sural nerve’s cross-sectional area (CSA) on the affected side (13 mm²) compared to the asymptomatic side (5 mm²). Notably, a positive Tinel’s sign was elicited over the psoriatic plaque. US-guided HD was performed using 50 cc of 5% dextrose in water (D5W) without local anesthetic below the psoriatic lesion. Post-HD, the patient reported immediate and significant pain relief (Numeric Pain Rating Scale (NPRS) score reduction from 8 to 2), confirming the prompt correction of a clinically important fascial restriction, associated with improved SN mobility, objectively verified by a post-procedure SDP assessment. At 24-month follow-up, sustained symptom relief and complete functional recovery were reported. Conclusions: This case highlights SDP’s ability to objectively visualize and confirm fascial restriction as a cause of nerve dysfunction by quantitatively reproducing concordant pain. The objective finding of nerve swelling provides sonographic substantiation for the functional diagnosis of nerve dysfunction. This integrated diagnostic approach, combining dynamic functional assessment with morphological confirmation, offers a novel paradigm for evaluating peripheral nerve disorders. US-guided HD of the SN with D5W without local anesthetic shows promise as both a diagnostic confirmatory tool and therapeutic intervention for neuropathic Achilles pain in psoriasis patients with SN involvement, aligning with its efficacy in other peripheral neuropathies. The significant nerve swelling (13 mm²) provides robust morphological corroboration of the functional impairment diagnosed by SDP, offering a more comprehensive diagnostic paradigm. Full article

(This article belongs to the Special Issue Ultrasound Diagnosis and Guided Intervention of Musculoskeletal/Neuromuscular Pathology, Second Edition)

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5 pages, 1635 KB

Open AccessInteresting Images

An Exceptional Case of Blow-Out Fracture with Complete Globe Dislocation into the Maxillary Sinus: Diagnostic Imaging and Surgical Reconstruction

by Krzysztof Gąsiorowski, Michał Gontarz, Jakub Bargiel, Tomasz Marecik and Grażyna Wyszyńska-Pawelec

Diagnostics 2025, 15(21), 2705; https://doi.org/10.3390/diagnostics15212705 (registering DOI) - 25 Oct 2025

Abstract

Orbital floor fractures are primarily caused by blunt trauma to the area around the eyes. These injuries most commonly affect the orbital floor and medial wall due to the fragility of these structures. The mechanism typically involves transmission of force through the orbital [...] Read more.

Orbital floor fractures are primarily caused by blunt trauma to the area around the eyes. These injuries most commonly affect the orbital floor and medial wall due to the fragility of these structures. The mechanism typically involves transmission of force through the orbital rim or an acute increase in intraorbital pressure caused by globe displacement. Blowout fractures often occur alongside additional maxillofacial fractures and periorbital soft tissue injuries. The reported causes mirror those of general maxillofacial trauma and include motor vehicle collisions, interpersonal violence, falls, sports-related injuries, incidents involving firearms, and occupational accidents. Here, we present the case of a 56-year-old male patient who sustained an exceptionally rare injury pattern characterized by a complete orbital floor fracture with globe dislocation into the maxillary sinus. Such extensive fractures are associated with significant functional impairments, including diplopia, enophthalmos, and restricted extraocular muscle movement, as well as marked aesthetic deformity. Comprehensive diagnostic imaging, comprising coronal, sagittal, and three-dimensional CT reconstructions, was crucial for accurately assessing the extent of bony disruption and soft tissue involvement. Particular emphasis should be placed on imaging that clearly delineates the extraocular muscles and the optic nerve, as precise evaluation of these structures is essential for surgical planning and prognosis. Surgical management involved repositioning of the globe and the orbital contents, followed by reconstruction of the orbital floor using a titanium mesh anchored to the infraorbital rim. This case highlights the technical challenges of total orbital floor reconstruction, emphasizing the importance of meticulous anatomical restoration for achieving optimal functional and aesthetic outcomes. Full article

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

12 pages, 1062 KB

Open AccessReview

Current Surgical Perspective on the Prognosis of Small-Cell Lung Cancer

by Hüseyin Fatih Sezer

Diagnostics 2025, 15(21), 2704; https://doi.org/10.3390/diagnostics15212704 (registering DOI) - 25 Oct 2025

Abstract

Small-cell lung cancer (SCLC) is a highly aggressive neuroendocrine tumour that can metastasise early, may show resistance to systemic treatment, and has a poor prognosis. The use of tobacco products is closely related to the duration of their use, and approximately 95% of [...] Read more.

Small-cell lung cancer (SCLC) is a highly aggressive neuroendocrine tumour that can metastasise early, may show resistance to systemic treatment, and has a poor prognosis. The use of tobacco products is closely related to the duration of their use, and approximately 95% of those diagnosed have a history of smoking. No satisfactory progress has been made in the prognosis with current treatment methods up to the present day. The treatment approach has traditionally involved long-term chemotherapy (CT) and radiotherapy (RT), and recent literature has focused on immunotherapy and genetic advancements. Surgery can only be performed in cases detected at an early stage. Although both chemotherapy and radiotherapy are indispensable options for most patients, their impact on prognosis and survival is limited. Although promising developments are expected in immunotherapy, its impact on survival is still very limited, lasting only about 2 months. In patients undergoing surgical resection as part of their treatment, overall survival (OS) ranges from 34 to 69 months. OS for 1 year is 84.8–93.8%, for 3 years is 60–71.2%, and for 5 years is 51.1–63.8%. The five-year survival rates are reported as follows: stage I 31–63.8%, stage II 25–65.5%, stage III 15–27.8%, and stage IV 0%. In this study, the prognosis and factors affecting prognosis in SCLC were investigated in light of current literature from a surgical perspective, and predictions were attempted to be made to lay the groundwork for personalised treatment approaches. Compared to non-small-cell lung cancer, the number of studies is quite limited. Most of the surgical case series were conducted in the past, retrospectively, and involved a small number of patients. Advances in immunotherapy are promising. In the early stages, resection and subsequent chemotherapy may be the main treatment. Full article

(This article belongs to the Special Issue Recent Advances in the Diagnosis and Prognosis of Lung Cancer)

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11 pages, 886 KB

Open AccessArticle

Quadratic Spline Fitting for Robust Measurement of Thoracic Kyphosis Using Key Vertebral Landmarks

by Nikola Kirilov and Elena Bischoff

Diagnostics 2025, 15(21), 2703; https://doi.org/10.3390/diagnostics15212703 (registering DOI) - 25 Oct 2025

Abstract

Objective: The purpose of this study is to present a kyphosis measurement method based on quadratic spline fitting through three key vertebral landmarks: T12, T8 and T4. This approach aims to capture thoracic spine curvature more continuously and accurately than traditional methods such [...] Read more.

Objective: The purpose of this study is to present a kyphosis measurement method based on quadratic spline fitting through three key vertebral landmarks: T12, T8 and T4. This approach aims to capture thoracic spine curvature more continuously and accurately than traditional methods such as the Cobb angle and circle fitting. Methods: A dataset of 560 lateral thoracic spine radiographs was retrospectively analyzed, including cases of postural kyphosis, Scheuermann’s disease, osteoporosis-induced kyphosis and ankylosing spondylitis. Two trained raters independently performed three repeated landmark annotations per image. The kyphosis angle was computed using two methods: (1) a quadratic spline fitted through the three landmarks, with the angle derived from tangent vectors at T12 and T4; and (2) a least-squares circle fit with the angle subtended between T12 and T4. Agreement with reference Cobb angles was evaluated using Pearson correlation, MAE, RMSE, ROC analysis and Bland–Altman plots. Reliability was assessed using intraclass correlation coefficients (ICC). Results: Both methods showed excellent intra- and inter-rater reliability (ICC ≥ 0.967). The spline method achieved lower MAE (5.81°), lower RMSE (8.94°) and smaller bias compared to the circle method. Both methods showed strong correlation with Cobb angles (r ≥ 0.851) and excellent classification performance (AUC > 0.950). Conclusions: Spline-based kyphosis measurement is accurate, reliable and particularly robust in cases with severe spinal deformity. Significance: This method supports automated, reproducible kyphosis assessment and may enhance clinical evaluation of spinal curvature using artificial intelligence-driven image analysis. Full article

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

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16 pages, 1814 KB

Open AccessReview

Descending Pain Modulation in Fibromyalgia: A Short Review of Mechanisms and Biomarkers

by Bruno Daniel Carneiro, Sandra Torres, José Tiago Costa-Pereira, Daniel Humberto Pozza and Isaura Tavares

Diagnostics 2025, 15(21), 2702; https://doi.org/10.3390/diagnostics15212702 (registering DOI) - 25 Oct 2025

Abstract

Fibromyalgia is a prevalent chronic pain disorder characterized by widespread musculoskeletal pain, fatigue, cognitive dysfunction, and sleep disturbances, with high impact in quality of life. Despite extensive research, the pathophysiological mechanisms of fibromyalgia remain partially understood, complicating the diagnosis and treatment. Some evidence [...] Read more.

Fibromyalgia is a prevalent chronic pain disorder characterized by widespread musculoskeletal pain, fatigue, cognitive dysfunction, and sleep disturbances, with high impact in quality of life. Despite extensive research, the pathophysiological mechanisms of fibromyalgia remain partially understood, complicating the diagnosis and treatment. Some evidence underscores the central role of abnormal pain processing, particularly central sensitization and defective descending pain modulation pathways. This review synthesizes and discusses current findings on the neurobiological underpinnings of pain in fibromyalgia, with focus on descending inhibitory control mechanisms and on the role of biomarkers. We integrate data from neurochemical, neuroimaging, and clinical studies to explain how impaired descending modulation contributes to enhanced pain sensitivity and discuss the putative biomarkers associated with changes in descending modulation. A better understanding of descending pain modulation dysfunction in fibromyalgia and related biomarkers is crucial for improving clinical outcomes and developing novel and more effective treatments. Full article

(This article belongs to the Special Issue Progress in Chronic Pain: Bridging Basic and Clinical Research)

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16 pages, 860 KB

Open AccessArticle

Impact of Preprocedural Collateral Status on Hemorrhagic Transformation and Outcomes After Endovascular Thrombectomy in Acute Ischemic Stroke

by Shiu-Yuan Huang, Nien-Chen Liao, Jin-An Huang, Wen-Hsien Chen and Hung-Chieh Chen

Diagnostics 2025, 15(21), 2701; https://doi.org/10.3390/diagnostics15212701 (registering DOI) - 25 Oct 2025

Abstract

Background: Hemorrhagic transformation (HT) is a major complication of endovascular thrombectomy (EVT) for acute ischemic stroke (AIS). Objectives: To investigate the factors as sociated with HT in patients with successful recanalization and examine the impact of collateral status (CS) on ischemic [...] Read more.

Background: Hemorrhagic transformation (HT) is a major complication of endovascular thrombectomy (EVT) for acute ischemic stroke (AIS). Objectives: To investigate the factors as sociated with HT in patients with successful recanalization and examine the impact of collateral status (CS) on ischemic progression and outcomes. Methods: We retrospectively analyzed patients with AIS with successful recanalization (modified treatment in cerebral infarction (mTICI) 2B-3) who underwent dual-energy CT (DECT) within 24 h and MRI within 10 days post-EVT. Patients with posterior circulation stroke, missing multiphase CT angiography (CTA) collateral scores, or missing 3-month modified ranking scale scores were excluded from the study. Results: Among the 86 patients, those with HT had a significantly lower proportion of 3-month excellent outcomes and worse imaging scores, including non-contrast CT (NCCT)-Alberta Stroke Program Early CT Score (ASPECTS), virtual non-contrast (VNC)-ASPECTS, and diffusion-weighted imaging (DWI)-ASPECTS. Patients with HT with poor CS had a significantly lower proportion of 3-month excellent outcomes, poorer post-EVT National Institutes of Health Stroke Scale (NIHSS) score, worse imaging scores, including VNC-ASPECTS, and DWI-ASPECTS. In the predictive factor analysis, post-EVT NIHSS and VNC-ASPECTS scores were significantly associated with 3-month excellent functional outcomes (modified Rankin Scale (mRS) 0-1). Conclusions: In patients with successfully recanalized AIS, HT with poor CS was associated with poorer functional outcomes and worse imaging scores, and a 24 h combined measure (post-EVT NIHSS and DECT VNC-ASPECT) show promise for early risk stratification; prospective external validation is warranted before routine use. Full article

(This article belongs to the Special Issue Cerebrovascular Lesions: Diagnosis and Management, 2nd Edition)

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15 pages, 475 KB

Open AccessArticle

Sensory Modulation Disorder as a Diagnostic Marker in Fibromyalgia: Associations with Stress and Symptom Severity

by Patricija Goubar and Tomaž Velnar

Diagnostics 2025, 15(21), 2700; https://doi.org/10.3390/diagnostics15212700 (registering DOI) - 24 Oct 2025

Abstract

Background/Objectives: Fibromyalgia (FM) is a nociplastic pain disorder marked by altered central nervous system processing and abnormal sensory modulation. Diagnosis remains largely symptom-based and lacks objective biomarkers. Sensory modulation disorder (SMD)—impaired regulation of responses to non-noxious input—may represent a clinically relevant diagnostic [...] Read more.

Background/Objectives: Fibromyalgia (FM) is a nociplastic pain disorder marked by altered central nervous system processing and abnormal sensory modulation. Diagnosis remains largely symptom-based and lacks objective biomarkers. Sensory modulation disorder (SMD)—impaired regulation of responses to non-noxious input—may represent a clinically relevant diagnostic dimension. This study aimed to estimate the prevalence/diagnostic value of SMD in FM, examine links with symptom severity and stress, and assess its potential for patient stratification. Methods: In this cross-sectional study, 182 adults were enrolled (104 FM; 78 controls). Standardized instruments included the Adolescent/Adult Sensory Profile (AASP), Fibromyalgia Impact Questionnaire (FIQ), and Perceived Stress Scale (PSS). Group comparisons, regression, and discriminant analyses evaluated SMD profiles. Results: Compared with controls, FM adults showed higher sensory sensitivity and avoidance (both p < 0.001), lower sensation seeking (p = 0.002), and modestly higher low registration (p = 0.027). Elevated SMD correlated with greater symptom severity and perceived stress. Stress significantly predicted FM’s impact (β = 0.57, p < 0.001). A discriminant model achieved 84% apparent in-sample accuracy for classifying FM severity from sensory/stress profiles. Conclusions: Sensory modulation abnormalities are highly prevalent in FM and show meaningful associations with symptom severity and stress, suggesting that SMD could represent a potential diagnostic dimension and stratification aid. These findings should be interpreted within an exploratory, cross-sectional design. Incorporating sensory modulation assessment into FM evaluation may improve diagnostic precision, reduce delays, and guide individualized management. Confirmation in larger longitudinal studies is warranted. Full article

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

11 pages, 722 KB

Open AccessArticle

Unraveling the Burden of Viral and Bacterial Central Nervous System Infections: A Two-Year Retrospective Study

by Nabeel Alzahrani, Ahmed Alshehri, Ali Alshehri and Sameera Al Johani

Diagnostics 2025, 15(21), 2699; https://doi.org/10.3390/diagnostics15212699 (registering DOI) - 24 Oct 2025

Abstract

Background/Objectives: Central nervous system (CNS) infections remain a significant public health challenge and require rapid and accurate diagnosis to guide clinical management. Although the incidence of bacterial meningitis has declined owing to widespread vaccination, viral etiologies continue to dominate CNS infections. The aim [...] Read more.

Background/Objectives: Central nervous system (CNS) infections remain a significant public health challenge and require rapid and accurate diagnosis to guide clinical management. Although the incidence of bacterial meningitis has declined owing to widespread vaccination, viral etiologies continue to dominate CNS infections. The aim of this study was to assess the epidemiological trends, age distribution, and seasonality of CNS infections using multiplex PCR. Methods: A retrospective analysis was conducted on cerebrospinal fluid (CSF) samples collected between January 2021 and December 2022 from patients with CNS infections at King Abdulaziz Medical City. A BioFire FilmArray Meningitis/Encephalitis (ME) panel was used to detect pathogens. Patient demographics, pathogen distribution, and seasonal trends were analyzed. Results: A total of 2,460 CSF samples were tested, of which 130 (5%) were positive for at least one pathogen. Viral pathogens accounted for 82.3% of the infections, with human herpesvirus-6 (HHV-6) (31%) and enterovirus (EV) (20%) being the most common. Bacterial pathogens represented 17.7% of the cases, with Streptococcus pneumoniae (6%) and Escherichia coli K1 (5%) being the predominant bacterial agents. The highest infection burden was observed in infants aged 0–6 months, with a marked male predominance. Seasonal analysis revealed multiple peaks in viral infections, particularly of HHV-6 and EVs, whereas bacterial infections were sporadic, with Streptococcus agalactiae and Streptococcus pneumoniae peaking in October and November. Conclusions: Viral infections, particularly HHV-6 and EVs, dominated CNS infections, with distinct seasonal and age-related variations. These findings underscore the value of multiplex PCR in improving the rapid diagnosis of CNS infections and aiding in timely treatment and antimicrobial stewardship. Full article

(This article belongs to the Section Clinical Laboratory Medicine)

17 pages, 1419 KB

Open AccessArticle

Optical Coherence Tomography Angiography (OCTA) Captures Early Micro-Vascular Remodeling in Non-Melanoma Skin Cancer During Superficial Radiotherapy: A Proof-of-Concept Study

by Gerd Heilemann, Giulia Rotunno, Lisa Krainz, Francesco Gili, Christoph Müller, Kristen M. Meiburger, Dietmar Georg, Joachim Widder, Wolfgang Drexler, Mengyang Liu and Cora Waldstein

Diagnostics 2025, 15(21), 2698; https://doi.org/10.3390/diagnostics15212698 (registering DOI) - 24 Oct 2025

Abstract

Background/Objectives: This proof-of-concept study evaluated whether optical coherence tomography angiography (OCTA) can non-invasively capture micro-vascular alterations in non-melanoma skin cancer (NMSC) lesions during and after superficial orthovoltage radiotherapy (RT) using radiomics and vascular features analysis. Methods: Eight patients (13 NMSC lesions) [...] Read more.

Background/Objectives: This proof-of-concept study evaluated whether optical coherence tomography angiography (OCTA) can non-invasively capture micro-vascular alterations in non-melanoma skin cancer (NMSC) lesions during and after superficial orthovoltage radiotherapy (RT) using radiomics and vascular features analysis. Methods: Eight patients (13 NMSC lesions) received 36–50 Gy in 6–20 fractions. High-resolution swept-source OCTA volumes (1.1 × 10 × 10 mm³) were acquired from each lesion at three time points: pre-RT, immediately post-RT, and three months post-RT. Additionally, healthy skin baseline was scanned. After artifact suppression and region-of-interest cropping, (i) first-order and texture radiomics and (ii) skeleton-based vascular features were extracted. Selected features after LASSO (least absolute shrinkage and selection operator) were explored with principal-component analysis. An XGBoost model was trained to classify time points with 100 bootstrap out-of-bag validations. Kruskal–Wallis tests with Benjamini–Hochberg correction assessed longitudinal changes in the 20 most influential features. Results: Sixty-one OCTA volumes were analyzable. LASSO retained 47 of 103 features. The first two principal components explained 63% of the variance, revealing a visible drift of lesions from pre- to three-month post-RT clusters. XGBoost achieved a macro-averaged AUC of 0.68 ± 0.07. Six features (3 texture, 2 first order, 1 vascular) changed significantly across time points (adjusted p < 0.05), indicating dose-dependent reductions in signal heterogeneity and micro-vascular complexity as early as treatment completion, which deepened by three months. Conclusions: OCTA-derived radiomic and vascular signatures tracked RT-induced micro-vascular remodeling in NMSC. The approach is entirely non-invasive, label-free, and feasible at the point of care. As an exploratory proof-of-concept, this study helps to refine scanning and analysis protocols and generates knowledge to support future integration of OCTA into adaptive skin-cancer radiotherapy workflows. Full article

(This article belongs to the Collection Biomedical Optics: From Technologies to Applications)

6 pages, 2063 KB

Open AccessInteresting Images

Perineurial Malignant Peripheral Nerve Sheath Tumor of the Cauda Equina: Diagnostic Challenge

by Tomonori Kawasaki, Tomoaki Torigoe, Takuya Watanabe, Satoshi Kanno, Masataka Hirasaki, Arisa Kokubo, Kojiro Onohara, Masanori Wako, Tetsuhiro Hagino and Jiro Ichikawa

Diagnostics 2025, 15(21), 2697; https://doi.org/10.3390/diagnostics15212697 (registering DOI) - 24 Oct 2025

Abstract

Malignant peripheral nerve sheath tumors (MPNSTs) are rare sarcomas with an extremely rare perineurial subtype. Herein, we present a case of a perineurial MPNST in the cauda equina. Clinically and radiologically, a mass extending from within the spinal canal at the L5 level [...] Read more.

Malignant peripheral nerve sheath tumors (MPNSTs) are rare sarcomas with an extremely rare perineurial subtype. Herein, we present a case of a perineurial MPNST in the cauda equina. Clinically and radiologically, a mass extending from within the spinal canal at the L5 level to outside the intervertebral foramen was identified, raising suspicion of a neurogenic tumor as the primary diagnosis. Computed tomography-guided biopsy suggested an intermediate- to low-grade malignancy; however, a definitive diagnosis could not be established. Two years later, worsening neurological symptoms prompted further imaging, which revealed significant tumor growth and bone invasion. Open biopsy was performed to obtain a definitive diagnosis of perineurial MPNST. MPNSTs lack distinctive imaging features and are generally diagnosed based on a combination of radiological and histopathological findings. Although MPNSTs have a poor prognosis, the perineurial subtype is considered to have a relatively favorable outcome. Given these factors, early diagnosis followed by surgical resection or radiation therapy is recommended. Full article

(This article belongs to the Special Issue Advanced Diagnosis and Integrated Management of Bone and Soft Tissue Tumors)

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15 pages, 1037 KB

Open AccessArticle

Dangerous Alarming Diameter Assessment (DADA Index) in Which the Ratio of Iris Surface/Pupil Surface Size Is More Reliable than Pupil Diameter Measurement in Comatose Patients After Subarachnoid Haemorrhage: An Experimental Rabbit Model

by Hüseyin Findik, Mehmet Dumlu Aydın, Feyzahan Uzun, Muhammet Kaim, Ayhan Kanat, Osman Nuri Keleş, Hakan Hadi Kadıoğlu, Mehmet Emin Akyüz and Mete Zeynal

Diagnostics 2025, 15(21), 2696; https://doi.org/10.3390/diagnostics15212696 (registering DOI) - 24 Oct 2025

Abstract

Objective/Background: Pupil diameter varies across individuals, limiting its reliability in assessing cerebral pathologies, particularly in comatose patients following subarachnoid haemorrhage (SAH). The Dangerous Alarming Diameter Assessment (DADA) index, defined as the ratio of iris surface to pupil surface, may offer a more precise [...] Read more.

Objective/Background: Pupil diameter varies across individuals, limiting its reliability in assessing cerebral pathologies, particularly in comatose patients following subarachnoid haemorrhage (SAH). The Dangerous Alarming Diameter Assessment (DADA) index, defined as the ratio of iris surface to pupil surface, may offer a more precise diagnostic tool. This study evaluates the efficacy of the DADA index compared to pupil diameter in predicting neurodegeneration in the Edinger–Westphal nucleus (EWN) and diagnosing brain death in an SAH model. Methods: Twenty-three rabbits were divided into Control (n = 5), Sham (n = 5), and Study (SAH, n = 12) groups. Pupil diameter and DADA index values were measured via spectral-domain optical coherence tomography (SD-OCT) in groups at post-intervention (0.75 cc serum physiologic injection for Sham, 0.75 cc autologous blood injection for Study). After one week, animals were sacrificed, and EWN degenerated neuron density was quantified using stereological methods. Data were analysed with Kruskal–Wallis and Mann–Whitney U tests, with correlations assessed for pupil diameter and DADA index against EWN neurodegeneration. Results: Pupil diameter assessment classified all 12 study group subjects as deceased, primarily due to fixed and dilated pupils. In contrast, the DADA index identified only 8 of these 12 subjects as deceased, with EWN degenerated neuron density exceeding 80%, while the remaining 4 subjects showed less than 80% neurodegeneration, indicating viability. Strong negative correlations were observed between pupil diameter (r = −0.972, p < 0.001) and DADA index (r = −0.977, p < 0.001) with EWN neurodegeneration. The DADA index demonstrated superior precision in distinguishing severe neurodegeneration, suggesting its potential as a criterion for brain death assessment. Conclusions: The DADA index provides a more accurate and nuanced evaluation of EWN neurodegeneration compared to pupil diameter, offering a promising diagnostic tool for brain death in SAH-induced comatose states, with potential implications for future brain transplantation diagnostics. Full article

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

26 pages, 1535 KB

Open AccessArticle

Prognostic and Predictive Significance of B7-H3 and CD155 Expression in Gastric Cancer Patients

by Ozlem Dalda, Zehra Bozdag, Sami Akbulut, Hasan Gokce, Yasin Dalda, Ayse Nur Akatli and Mustafa Huz

Diagnostics 2025, 15(21), 2695; https://doi.org/10.3390/diagnostics15212695 (registering DOI) - 24 Oct 2025

Abstract

Background/Objectives: This study aimed to characterize the expression patterns of B7 homolog 3 (B7-H3) and cluster of differentiation 155 (CD155), two immune-related transmembrane glycoproteins, in resectable gastric adenocarcinoma and to elucidate their clinicopathological, prognostic, and molecular implications. Methods: The study included [...] Read more.

Background/Objectives: This study aimed to characterize the expression patterns of B7 homolog 3 (B7-H3) and cluster of differentiation 155 (CD155), two immune-related transmembrane glycoproteins, in resectable gastric adenocarcinoma and to elucidate their clinicopathological, prognostic, and molecular implications. Methods: The study included 112 patients who underwent gastrectomy for gastric adenocarcinoma between 2020 and 2025, along with 30 samples of normal gastric tissue obtained from sleeve gastrectomy specimens. Histological subtype, grade of differentiation, TNM stage, and invasion parameters were re-evaluated. Immunohistochemical expression of B7-H3 and CD155 was quantified for membranous, stromal and membranous/cytoplasmic staining patterns. Quantitative reverse transcription polymerase chain reaction (RT-PCR) was performed on 29 tumor and 25 normal samples to confirm mRNA expression levels, with fold change ≥2 considered biologically significant upregulation and ≤0.5 considered downregulation. Machine learning models were developed to predict metastasis and mortality based on clinical and immunohistochemical features. Results: 78.5% of tumors were at an advanced stage (T3–T4), and metastasis was present in 22.3% of patients. Perineural invasion (PNI) and lymphovascular invasion (LVI) were observed in 67.9% and 88.4% of cases, respectively. Increased B7-H3 and CD155 expression were significantly associated with advanced tumor stage, metastasis, and the presence of PNI and LVI (all p < 0.05). In metastatic tumors, median membranous B7-H3, stromal B7-H3, and CD155 scores were 60, 130, and 190, respectively, compared with 20, 90, and 120 in non-metastatic tumors. A significant positive correlation was found between stromal B7-H3 and CD155 expression (r = 0.384, p < 0.001), indicating parallel upregulation. Quantitative RT-PCR confirmed significant overexpression of both genes in tumor tissues relative to normal controls. B7-H3 was upregulated in 75.9% and CD155 in 58.6% of samples, with co-upregulation in 55.2%. Fold-change levels were markedly higher in metastatic versus non-metastatic cases (B7-H3: 7.69-fold vs. 3.04-fold; CD155: 7.44-fold vs. 1.79-fold). ML analysis using the XGBoost model achieved 91.1% accuracy for metastasis prediction (F1-score 0.800). Key variables included pathological T4b stage, perineural invasion, N3b status, T4a stage, and CD155 score. The mortality model yielded 86.7% accuracy (F1-score 0.864), with metastasis, differentiation status, nodal involvement, age, lymph node ratio, and perineural invasion emerging as principal predictors. Conclusions: Combined evaluation of B7-H3 and CD155, supported by immunohistochemical staining and RT-PCR quantification of B7-H3 and CD155 mRNA expression levels, provides meaningful prognostic insights and supports their potential as dual molecular biomarkers for aggressive gastric adenocarcinoma phenotypes. Full article

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

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9 pages, 760 KB

Open AccessArticle

Variability of ChatGPT in Interpreting the Lexicon of ACR-TIRADS, EU-TIRADS, and K-TIRADS

by Pierpaolo Trimboli, Amos Colombo, Lorenzo Ruinelli and Andrea Leoncini

Diagnostics 2025, 15(21), 2694; https://doi.org/10.3390/diagnostics15212694 (registering DOI) - 24 Oct 2025

Abstract

Background: There is an ongoing project to create an international Thyroid Imaging Reporting And Data System (I-TIRADS) to harmonize the terminology of guidelines for reporting thyroid ultrasonography. As artificial intelligence (AI) has been gaining increasing attention also in the thyroid field, achieving solid [...] Read more.

Background: There is an ongoing project to create an international Thyroid Imaging Reporting And Data System (I-TIRADS) to harmonize the terminology of guidelines for reporting thyroid ultrasonography. As artificial intelligence (AI) has been gaining increasing attention also in the thyroid field, achieving solid information about the consistency of AI in interpreting the TIRADS terminology is relevant before the I-TIRADS is published. The present study aimed to examine the issue of AI when interpreting the TIRADS terminology to describe thyroid nodules (TNs). Methods: Three TIRADSs from the USA (ACR-TIRADS), Europe (EU-TIRADS), and Asia (K-TIRADS) were considered. The most popular AI, such as ChatGPT, was tested. All possible combinations of terms of the three TIRADSs were performed. Results: 2592 cases were included. With the ACR-TIRADS lexicon, there was a slightly significant difference between systems (p = 0.0494) which was attributed to variations between ACR- and EU-TIRADS (p = 0.0099). With the EU-TIRADS lexicon, there was a significant difference between systems (p < 0.0001) with a significant result between EU- and ACR-TIRADS (p = 0.0003). Using the K-TIRADS terminology, no significant difference was observed (p = 0.7954). The intraobserver agreement of ChatGPT was moderate with the best values (from 0.55 to 0.60) with the K-TIRADS lexicon. Conclusions: ChatGPT interprets the TIRADS lexicon but with variations when it is asked to assess TNs according to one TIRADS using the terminology of another TIRADS. Clinical operators as well as patients should also be aware of these novel data. Full article

(This article belongs to the Special Issue The Future of Diagnostics: Exploring the Role of Artificial Intelligence in Medicine)

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18 pages, 1432 KB

Open AccessArticle

Machine Learning-Based Prediction of Three-Year Heart Failure and Mortality After Premature Ventricular Contraction Ablation

by Chung-Yu Lin, Yu-Te Lai, Chien-Wei Chuang, Chih-Hsien Yu, Chiung-Yun Lo, Mingchih Chen and Ben-Chang Shia

Diagnostics 2025, 15(21), 2693; https://doi.org/10.3390/diagnostics15212693 (registering DOI) - 24 Oct 2025

Abstract

Introduction: Long-term heart failure and mortality after catheter ablation for premature ventricular contraction (PVC) remain underexplored. Methods: We retrospectively analyzed 4195 adults who underwent PVC ablation in a nationwide claims database. To address class imbalance, we used synthetic minority over-sampling technique (SMOTE) and [...] Read more.

Introduction: Long-term heart failure and mortality after catheter ablation for premature ventricular contraction (PVC) remain underexplored. Methods: We retrospectively analyzed 4195 adults who underwent PVC ablation in a nationwide claims database. To address class imbalance, we used synthetic minority over-sampling technique (SMOTE) and random over-sampling examples (ROSE). Five supervised algorithms were compared: logistic regression, decision tree, random forest, XGBoost, and LightGBM. Discrimination was assessed by stratified five-fold cross-validation using the area under the receiver operating characteristic curve (ROC AUC). Because rare events can bias ROC, we also examined precision–recall (PR) curves. Results: For predicting three-year heart failure, LightGBM with ROSE achieved the highest ROC AUC at 0.822. For three-year mortality, logistic regression with ROSE and LightGBM with ROSE showed balanced performance with ROC AUCs of 0.886 and 0.882. Pairwise DeLong tests indicated that these leading models formed a high-performing cluster without significant differences in ROC AUC. Age, prior heart failure, malignancy, and end-stage renal disease were the most influential predictors by model explainability analysis. Discussion: Addressing class imbalance and benchmarking modern learners against a transparent logistic baseline yielded robust, clinically interpretable risk stratification after PVC ablation. These models are suitable for integration into electronic health record dashboards, with external validation and local threshold optimization as next steps. Full article

(This article belongs to the Special Issue New Advances in Cardiovascular Risk Prediction)

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34 pages, 385 KB

Open AccessReview

Machine Learning in MRI Brain Imaging: A Review of Methods, Challenges, and Future Directions

by Martyna Ottoni, Anna Kasperczuk and Luis M. N. Tavora

Diagnostics 2025, 15(21), 2692; https://doi.org/10.3390/diagnostics15212692 (registering DOI) - 24 Oct 2025

Abstract

In recent years, machine learning (ML) has been increasingly used in many fields, including medicine. Magnetic resonance imaging (MRI) is a non-invasive and effective diagnostic technique; however, manual image analysis is time-consuming and prone to human variability. In response, ML models have been [...] Read more.

In recent years, machine learning (ML) has been increasingly used in many fields, including medicine. Magnetic resonance imaging (MRI) is a non-invasive and effective diagnostic technique; however, manual image analysis is time-consuming and prone to human variability. In response, ML models have been developed to support MRI analysis, particularly in segmentation and classification tasks. This work presents an updated narrative review of ML applications in brain MRI, with a focus on tumor classification and segmentation. A literature search was conducted in PubMed and Scopus databases and Mendeley Catalog (MC)—a publicly accessible bibliographic catalog linked to Elsevier’s Scopus indexing system—covering the period from January 2020 to April 2025. The included studies focused on patients with primary or secondary brain neoplasms and applied machine learning techniques to MRI data for classification or segmentation purposes. Only original research articles written in English and reporting model validation were considered. Studies using animal models, non-imaging data, lacking proper validation, or without accessible full texts (e.g., abstract-only records or publications unavailable through institutional access) were excluded. In total, 108 studies met all inclusion criteria and were analyzed qualitatively. In general, models based on convolutional neural networks (CNNs) were found to dominate current research due to their ability to extract spatial features directly from imaging data. Reported classification accuracies ranged from 95% to 99%, while Dice coefficients for segmentation tasks varied between 0.83 and 0.94. Hybrid architectures (e.g., CNN-SVM, CNN-LSTM) achieved strong results in both classification and segmentation tasks, with accuracies above 95% and Dice scores around 0.90. Transformer-based models, such as the Swin Transformer, reached the highest performance, up to 99.9%. Despite high reported accuracy, challenges remain regarding overfitting, generalization to real-world clinical data, and lack of standardized evaluation protocols. Transfer learning and data augmentation were frequently applied to mitigate limited data availability, while radiomics-based models introduced new avenues for personalized diagnostics. ML has demonstrated substantial potential in enhancing brain MRI analysis and supporting clinical decision-making. Nevertheless, further progress requires rigorous clinical validation, methodological standardization, and comparative benchmarking to bridge the gap between research settings and practical deployment. Full article

(This article belongs to the Special Issue Brain/Neuroimaging 2025–2026)

23 pages, 2069 KB

Open AccessArticle

Early Lung Cancer Detection via AI-Enhanced CT Image Processing Software

by Joel Silos-Sánchez, Jorge A. Ruiz-Vanoye, Francisco R. Trejo-Macotela, Marco A. Márquez-Vera, Ocotlán Diaz-Parra, Josué R. Martínez-Mireles, Miguel A. Ruiz-Jaimes and Marco A. Vera-Jiménez

Diagnostics 2025, 15(21), 2691; https://doi.org/10.3390/diagnostics15212691 (registering DOI) - 24 Oct 2025

Abstract

Background/Objectives: Lung cancer remains the leading cause of cancer-related mortality worldwide among both men and women. Early and accurate detection is essential to improve patient outcomes. This study explores the use of artificial intelligence (AI)-based software for the diagnosis of lung cancer through [...] Read more.

Background/Objectives: Lung cancer remains the leading cause of cancer-related mortality worldwide among both men and women. Early and accurate detection is essential to improve patient outcomes. This study explores the use of artificial intelligence (AI)-based software for the diagnosis of lung cancer through the analysis of medical images in DICOM format, aiming to enhance image visualization, preprocessing, and diagnostic precision in chest computed tomography (CT) scans. Methods: The proposed system processes DICOM medical images converted to standard formats (JPG or PNG) for preprocessing and analysis. An ensemble of classical machine learning algorithms—including Random Forest, Gradient Boosting, Support Vector Machine, and K-Nearest Neighbors—was implemented to classify pulmonary images and predict the likelihood of malignancy. Image normalization, denoising, segmentation, and feature extraction were performed to improve model reliability and reproducibility. Results: The AI-enhanced system demonstrated substantial improvements in diagnostic accuracy and robustness compared with individual classifiers. The ensemble model achieved a classification accuracy exceeding 90%, highlighting its effectiveness in identifying malignant and non-malignant lung nodules. Conclusions: The findings indicate that AI-assisted CT image processing can significantly contribute to the early detection of lung cancer. The proposed methodology enhances diagnostic confidence, supports clinical decision-making, and represents a viable step toward integrating AI into radiological workflows for early cancer screening. Full article

(This article belongs to the Special Issue Application of Machine Learning in Disease Screening, Diagnosis and Prognosis)

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9 pages, 648 KB

Open AccessArticle

Clinical Characteristics of Seizures and Course of Epilepsy in Children with Neurofibromatosis Type 1—A Tertiary Center Experience in a Cohort of 118 Children

by Ružica Kravljanac, Jovana Beđik, Irene Bruno, Biljana Vučetić Tadić, Sofija Popović, Vladimir Oparnica and Pavle Kravljanac

Diagnostics 2025, 15(21), 2690; https://doi.org/10.3390/diagnostics15212690 (registering DOI) - 24 Oct 2025

Abstract

Background/Objectives: This study aimed to improve the knowledge of seizures and epilepsy in children with neurofibromatosis type 1 (NF1) by evaluating the frequency, clinical characteristics, and risk for epilepsy in children with NF1. Methods: The retrospective study included all NF1 patients [...] Read more.

Background/Objectives: This study aimed to improve the knowledge of seizures and epilepsy in children with neurofibromatosis type 1 (NF1) by evaluating the frequency, clinical characteristics, and risk for epilepsy in children with NF1. Methods: The retrospective study included all NF1 patients aged one month to 18 years treated at the Institute from 2010 to 2025, who experienced seizures. Diagnosis of NF1 was made using revised diagnostic criteria from 2021. The seizures were classified according to the ILAE classification, updated in 2025. Further parameters were analyzed: sex, age at seizure onset, type and duration, electroencephalographic (EEG) findings, brain magnetic-resonance imaging (MRI), anti-seizure medications (ASMs), treatment response, and outcome. The patients were divided into two groups: epilepsy—NF1 patients (14) and non-epilepsy—NF1 patients (104). To evaluate the predictive factors for epilepsy in NF1 patients, univariate and multivariate logistic regression analyses were performed. Results: The study included 118 children with NF1. In 14 children (11.9%), a diagnosis of epilepsy was established. Ten of 14 children (71.4%) experienced SE. Good seizure control was achieved in 13/14. We found statistically significant predictive values of hydrocephalus (p = 0.001), brain atrophy (p = 0.002), and vasculopathy (p = 0.015) for epilepsy in children with NF1. Conclusions: In our cohort, the frequency of epilepsy in NF children was at least ten times higher than in the general population. The predictive factors for epilepsy were hydrocephalus, brain atrophy, and vasculopathy. Recommendations for rescue medication and parental education are important, since status epilepticus occurs in a high percentage of NF1 patients with epilepsy. Full article

(This article belongs to the Special Issue Neurofibromatosis and Schwannomatosis: Diagnosis and Management)

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21 pages, 1246 KB

Open AccessArticle

Evaluation of the Relationship Between Neurologic Manifestations and Genetic Mutations in Wilson’s Disease with Next-Generation Sequencing

by Sami Akbulut, Seyma Is, Tugba Kul Koprulu, Fatma Ilknur Varol, Zeynep Kucukakcali, Cemil Colak, Ahmet Koc, Saban Tekin and Sezai Yilmaz

Diagnostics 2025, 15(21), 2689; https://doi.org/10.3390/diagnostics15212689 - 24 Oct 2025

Abstract

Background: Wilson’s disease (WD) is a rare autosomal recessive disorder caused by mutations in the ATP7B gene, leading to copper accumulation in the liver and brain. Given the clinical heterogeneity of the disease, this study aimed to characterize the mutational spectrum of [...] Read more.

Background: Wilson’s disease (WD) is a rare autosomal recessive disorder caused by mutations in the ATP7B gene, leading to copper accumulation in the liver and brain. Given the clinical heterogeneity of the disease, this study aimed to characterize the mutational spectrum of ATP7B and explore genotype–phenotype correlations in Turkish patients. Methods: Whole-exome sequencing (WES) was performed in 17 Turkish patients clinically diagnosed with WD. Variants were annotated and evaluated using five in silico prediction tools (REVEL, CADD, PolyPhen, SIFT, MutationTaster). Copy number variation (CNV) analysis was conducted using the CLC Genomics Server (Version 22.0.2). Results: A total of 14 distinct ATP7B variants were identified, comprising 12 missense, 1 nonsense, and 1 frameshift mutation. Variant distribution showed some phenotype-specific patterns: four variants were found more frequently in hepatic cases and three in neurological cases, although no statistically significant or consistent correlation between genotype and clinical presentation could be established. The most frequent mutation was p.His1069Gln, present in both phenotypes. All missense variants were predicted to be pathogenic by at least three computational tools, with high concordance among platforms. No pathogenic CNVs were detected. Conclusions: This study expands the mutational landscape of ATP7B in Turkish patients with WD and supports the utility of WES combined with in silico tools for accurate variant classification. The results emphasize the genetic heterogeneity of WD and suggest possible associations between certain mutations and clinical phenotypes. Full article

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

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14 pages, 2571 KB

Open AccessReview

Exploring Morphologic and Functional Variants in Hypertrophic Cardiomyopathy: An Echocardiographic and Doppler Review

by Kamil Stankowski, Fabrizio Celeste, Manuela Muratori, Francesco Cannata, Nicola Cosentino, Fabio Fazzari, Laura Fusini, Daniele Junod, Massimo Mapelli, Riccardo Maragna, Andrea Baggiano, Saima Mushtaq, Luigi Tassetti, Gianluca Pontone and Mauro Pepi

Diagnostics 2025, 15(21), 2688; https://doi.org/10.3390/diagnostics15212688 - 24 Oct 2025

Abstract

Hypertrophic cardiomyopathy (HCM) is a complex and heterogeneous myocardial disorder, best evaluated with echocardiography for initial diagnosis, risk stratification, and longitudinal monitoring. This focused review explores the echocardiographic assessment of various morphologic phenotypes of HCM, emphasizing their diagnostic nuances. Distinct phenotypes, including asymmetric [...] Read more.

Hypertrophic cardiomyopathy (HCM) is a complex and heterogeneous myocardial disorder, best evaluated with echocardiography for initial diagnosis, risk stratification, and longitudinal monitoring. This focused review explores the echocardiographic assessment of various morphologic phenotypes of HCM, emphasizing their diagnostic nuances. Distinct phenotypes, including asymmetric septal hypertrophy, concentric hypertrophy, and the less common apical HCM, present unique imaging challenges. Additionally, the review outlines essential techniques and practical tips for assessing left ventricular apical aneurysm flow patterns and dynamic intraventricular gradients. A thorough understanding of mitral valve anatomy and its role in left ventricular outflow tract obstruction is also crucial. Finally, anatomical variants of the mitral valve, papillary muscles and left ventricular myocardium are examined for their contribution to systolic anterior motion and mid-ventricular obstruction as well as for constituting additional phenotypical expressions of HCM, beyond left ventricular hypertrophy. Full article

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

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15 pages, 4435 KB

Open AccessCase Report

Renal Hypoplasia and Oligomeganephronia in a Fetus with Wolf–Hirschhorn Syndrome

by Maria Paola Bonasoni, Mariangela Pati, Khush Shah, Andrea Musarò, Immacolata Blasi, Flavio Vanacore, Giovanna Botticelli, Veronica Barbieri, Veronica Bizzarri, Maria Marinelli, Moira Foroni, Lorenzo Aguzzoli and Marzia Pollazzon

Diagnostics 2025, 15(21), 2687; https://doi.org/10.3390/diagnostics15212687 - 24 Oct 2025

Abstract

Background and Clinical Significance: Wolf–Hirschhorn syndrome (WHS, OMIM #194190) is caused by deletion of the distal short arm of chromosome 4. It is characterized by intrauterine growth restriction (IUGR), developmental delay, epilepsy, distinctive facial features, and urinary tract anomalies, particularly renal hypoplasia. [...] Read more.

Background and Clinical Significance: Wolf–Hirschhorn syndrome (WHS, OMIM #194190) is caused by deletion of the distal short arm of chromosome 4. It is characterized by intrauterine growth restriction (IUGR), developmental delay, epilepsy, distinctive facial features, and urinary tract anomalies, particularly renal hypoplasia. However, the histological profile of renal involvement in WHS is rarely documented. Case presentation: We report a case of fetal WHS with renal hypoplasia and histological evidence of oligomeganephronia (OMN). At 21 weeks’ gestation, a prenatal ultrasound revealed oligo/anhydramnios and IUGR. Genetic testing (karyotype and CGH-array) confirmed a de novo 17.92 Mb terminal deletion from 4p16.3 to 4p15.31. The pregnancy was legally terminated at 23 weeks. The autopsy showed characteristic WHS dysmorphisms, growth restriction, and markedly small kidneys. Histology revealed OMN with a thinned renal cortex with reduced glomeruli, mainly hypoplastic, some of which were hypertrophic, and dilated proximal tubules. Scattered medullary tubules were present within the tubulointerstitial compartment, alongside thickened tubular basement membranes highlighted by Collagen IV staining. Conclusions: This case suggests that OMN may be a histological hallmark of renal hypoplasia in WHS, especially in larger 4p deletions. Recognizing this pattern may help with prenatal prognosis and clinical management. Further studies are needed to confirm this association. Full article

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

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18 pages, 1004 KB

Open AccessCase Report

Vesicovaginal Leiomyoma at 20 Years of Age—A Rare Clinical Entity: Case Report and Literature Review

by Carmen Elena Bucuri, Răzvan Ciortea, Andrei Mihai Măluțan, Aron Valentin Oprea, Maria Patricia Roman, Cristina Mihaela Ormindean, Ionel Daniel Nati, Viorela Elena Suciu, Alex Emil Hăprean and Dan Mihu

Diagnostics 2025, 15(21), 2686; https://doi.org/10.3390/diagnostics15212686 - 24 Oct 2025

Abstract

Background and Clinical Significance: Vesicovaginal leiomyomas are an exceedingly rare form of extrauterine fibroids. They represent less than 1% of all leiomyomas and have been reported in less than 300 cases worldwide since 1733. These benign smooth muscle tumors typically occur in perimenopausal [...] Read more.

Background and Clinical Significance: Vesicovaginal leiomyomas are an exceedingly rare form of extrauterine fibroids. They represent less than 1% of all leiomyomas and have been reported in less than 300 cases worldwide since 1733. These benign smooth muscle tumors typically occur in perimenopausal women aged 35–50 years, presenting in young adults extraordinarily uncommonly. The rarity in younger patients creates significant diagnostic challenges, as clinical presentation often mimics malignant entities, particularly embryonal rhabdomyosarcoma. Case Presentation: This paper presents a 20-year-old nulliparous female who developed progressive dyspareunia and urinary dysfunction over 12 months due to a large vesicovaginal mass. Physical examination revealed a 6–7 cm smooth, firm mass obstructing the vaginal canal. Transvaginal ultrasound demonstrated a well-circumscribed, hypoechoic solid lesion measuring 6.9 cm in the vesicovaginal space. Magnetic resonance imaging showed a characteristic T2-hypointense signal with restricted diffusion consistent with leiomyoma, revealing an incidental septate uterus. Ultrasound-guided core needle biopsy confirmed benign leiomyoma with bland spindle cells, absent atypia, and minimal mitotic activity. The patient underwent successful transvaginal enucleation with complete symptom resolution. Conclusion: This case highlights diagnostic challenges posed by benign leiomyomas in young women presenting with solid pelvic masses. Systematic diagnostic approaches incorporating multimodal imaging and guided tissue sampling are essential to avoid misdiagnosis and unnecessary radical surgery. When malignancy is confidently excluded, management should prioritize fertility preservation in young patients. Full article

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

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15 pages, 1889 KB

Open AccessArticle

Predicting Sarcopenia in Peritoneal Dialysis Patients: A Multimodal Ultrasound-Based Logistic Regression Analysis and Nomogram Model

by Shengqiao Wang, Xiuyun Lu, Juan Chen, Xinliang Xu, Jun Jiang and Yi Dong

Diagnostics 2025, 15(21), 2685; https://doi.org/10.3390/diagnostics15212685 - 23 Oct 2025

Abstract

Objective: This study aimed to evaluate the diagnostic value of logistic regression and nomogram models based on multimodal ultrasound in predicting sarcopenia in patients with peritoneal dialysis (PD). Methods: A total of 178 patients with PD admitted to our nephrology department between June [...] Read more.

Objective: This study aimed to evaluate the diagnostic value of logistic regression and nomogram models based on multimodal ultrasound in predicting sarcopenia in patients with peritoneal dialysis (PD). Methods: A total of 178 patients with PD admitted to our nephrology department between June 2024 and April 2025 were enrolled. According to the 2019 Asian Working Group for Sarcopenia (AWGS) diagnostic criteria, patients were categorized into sarcopenia and non-sarcopenia groups. Ultrasound examinations were used to measure the muscle thickness (MT), pinna angle (PA), fascicle length (FL), attenuation coefficient (Atten Coe), and echo intensity (EI) of the right gastrocnemius medial head. The clinical characteristics of the groups were compared using the Mann–Whitney U test. Binary logistic regression was used to identify sarcopenia risk factors to construct clinical prediction models and nomograms. Receiver operating characteristic (ROC) curves were used to assess the model accuracy and stability. Results: The sarcopenia group exhibited significantly lower MT, PA, and FL, but higher Atten Coe and EI than the non-sarcopenia group (all p < 0.05). A multimodal ultrasound logistic regression model was developed using machine learning—Logit(P) = −7.29 − 1.18 × MT − 0.074 × PA + 0.48 × FL + 0.52 × Atten Coe + 0.13 × EI (p < 0.05)—achieving an F1-score of 0.785. The area under the ROC curve (ROC-AUC) was 0.902, with an optimal cut-off value of 0.45 (sensitivity 77.3%, specificity 56.7%). Nomogram consistency analysis showed no statistical difference between the ultrasound diagnosis and the appendicular skeletal muscle index (ASMI) measured by bioelectrical impedance analysis (BIA) (Z = 0.415, p > 0.05). Conclusions: The multimodal ultrasound-based prediction model effectively assists clinicians in identifying patients with PD at a high risk of sarcopenia, enabling early intervention to improve clinical outcomes. Full article

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

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32 pages, 14260 KB

Open AccessSystematic Review

Efficacy of Percutaneous Vertebroplasty Versus Placebo and Conservative Treatment in Osteoporotic Vertebral Fractures: An Updated Systematic Review and Meta-Analysis of Randomized Clinical Trials

by Antonio Jesús Láinez Ramos-Bossini, Francisco Garrido Sanz, Marina Gea Becerra, Consolación Melguizo Alonso, José Prados, Fernando Ruiz Santiago and José Manuel Benítez

Diagnostics 2025, 15(21), 2684; https://doi.org/10.3390/diagnostics15212684 - 23 Oct 2025

Abstract

Introduction: The efficacy of percutaneous vertebroplasty (PV) versus placebo and conservative treatment (CT) in patients with osteoporotic vertebral fractures (OVFs) has been debated in recent years. The aim of this study was to conduct an updated systematic review with a meta-analysis on the [...] Read more.

Introduction: The efficacy of percutaneous vertebroplasty (PV) versus placebo and conservative treatment (CT) in patients with osteoporotic vertebral fractures (OVFs) has been debated in recent years. The aim of this study was to conduct an updated systematic review with a meta-analysis on the efficacy of randomized controlled trials (RCTs) comparing PV versus placebo and CT in pain relief, functionality and quality of life in patients with OVFs. Methods: A systematic search was conducted in PubMed, Web of Science, EMBASE, and CENTRAL, resulting in a total of 15 RCTs. The risk of bias was assessed using the Risk of Bias v.2 tool. A meta-analysis was performed using the weighted inverse variance method to analyze the standardized mean difference (SMD) in pain (VAS/NRS scales), functionality (RMDQ/ODI scales) and quality of life (QUALEFFO scale) in the short (<1 month), medium (1–6 months) and long terms (≥6 months). Heterogeneity was assessed using I² and τ². Subgroup analyses were performed according to the type of control, geographic region, number of institutions, fracture chronicity, and risk of bias. In addition, sensitivity (leave-one-out) and publication bias (funnel plots and Egger’s tests) analyses were performed. Results: Overall, PV showed benefits over the combined control groups in pain relief in the short (SMD: −0.68; 95%CI: −1.28–−0.07), medium (SMD: −0.63; 95%CI: −1.18–−0.07), and long terms (SMD: −0.59; 95%CI: −1.02–−0.15). No statistically significant differences were found in functionality and quality of life, although several trends toward significance were observed favoring PV. Subgroup analyses showed greater advantages of PV at several time intervals in acute (<8 weeks) OVFs, multicentric trials and studies with a low risk of bias. There were cues suggestive of potential publication bias in functionality, but not in pain or quality of life. Conclusions: PV shows significant benefits in pain relief, particularly in acute OVFs, but its efficacy in terms of functionality and quality of life remains unclear. These results support the use of PV in appropriately selected patients. However, given the high heterogeneity found, more controlled, multicenter trials are still required. Full article

(This article belongs to the Special Issue Advancements in the Diagnostics and Management of Musculoskeletal Diseases)

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6 pages, 3663 KB

Open AccessInteresting Images

A Multi-Modality Approach to the Assessment of a Right Atrium Mass in a Female Patient with Breast Cancer Undergoing Neoadjuvant Chemotherapy

by Małgorzata Chlabicz, Paweł Muszyński, Joanna Kruszyńska, Piotr Kazberuk, Magdalena Róg-Makal, Magdalena Lipowicz, Urszula Matys, Anna Tomaszuk-Kazberuk, Marcin Kożuch and Sławomir Dobrzycki

Diagnostics 2025, 15(21), 2683; https://doi.org/10.3390/diagnostics15212683 - 23 Oct 2025

Abstract

Echocardiography remains a vital part of the initial assessment and monitoring of oncological patients. It allows for proper treatment selection but can also reveal life-threatening complications, including impaired left ventricular function or thromboembolism. It can rarely detect intracardiac masses that require further investigation. [...] Read more.

Echocardiography remains a vital part of the initial assessment and monitoring of oncological patients. It allows for proper treatment selection but can also reveal life-threatening complications, including impaired left ventricular function or thromboembolism. It can rarely detect intracardiac masses that require further investigation. In the presented case, a 51-year-old female patient with left-sided breast cancer, who had undergone neoadjuvant chemotherapy, was hospitalised due to a right atrial mass identified via routine transthoracic echocardiography (TTE). Initial anticoagulation therapy showed no clinical improvement. Follow-up TTE revealed a 12 × 19 mm hyperechogenic, mobile mass in the right atrium (RA). Computed tomography angiography (CTA) ruled out pulmonary embolism and revealed that the mass was located close to the tip of the vascular access port. Transoesophageal echocardiography showed that the lesion was not connected to the vascular port. Based on location and mobility, the lesion was most consistent with a cardiac myxoma. After the Heart Team made a decision, endovascular intervention using a vacuum-assisted device was performed without complications. Histopathological examination excluded thrombosis and myxoma, revealing a fibro-inflammatory lesion. A multimodality approach is necessary to assess RA masses. However, even an extensive evaluation could be misleading, so treatment options should always be subject to the Heart Team’s decision. Full article

(This article belongs to the Special Issue The Future of Cardiac Imaging in the Diagnosis, 2nd Edition)

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15 pages, 882 KB

Open AccessArticle

Diagnostic Performance of the Triglyceride-Glucose Index in Screening for Gestational Diabetes Mellitus at 24–28 Weeks of Gestation

by Saliha Sağnıç, Tuğba Gül Yılmaz, Addule Serhanoğlu Seçen, Mustafa Bağcı, Selin Güney, Mert Cenker Güney and Ayşegül Atalay

Diagnostics 2025, 15(21), 2682; https://doi.org/10.3390/diagnostics15212682 - 23 Oct 2025

Abstract

Background/Objectives: The objective of this study was to assess the diagnostic accuracy of the Triglyceride-Glucose (TyG) index for screening gestational diabetes mellitus (GDM) at 24–28 weeks of gestation, to determine its optimal diagnostic threshold, and to compare its predictive performance with conventional [...] Read more.

Background/Objectives: The objective of this study was to assess the diagnostic accuracy of the Triglyceride-Glucose (TyG) index for screening gestational diabetes mellitus (GDM) at 24–28 weeks of gestation, to determine its optimal diagnostic threshold, and to compare its predictive performance with conventional lipid ratios (LDL/HDL, TG/HDL, and TC/HDL). Materials and Methods: We retrospectively analyzed 440 pregnant women with singleton pregnancies who underwent a 75 g oral glucose tolerance test (OGTT) between January and July 2025. The TyG index and lipid ratios were calculated, and their associations with GDM were evaluated. Subgroup analyses were conducted to assess the efficacy of the TyG index in predicting GDM, using logistic regression to estimate odds ratios (ORs) with 95% confidence intervals (CIs), and receiver operating characteristic (ROC) curve analysis along with restricted cubic spline modeling to evaluate diagnostic performance and determine the optimal cutoff value. Results: The overall prevalence of GDM, as defined by the IADPSG (International Association of the Diabetes and Pregnancy Study Groups) criteria, was 22.7%. The median TyG index was significantly higher in the GDM group compared with the non-GDM group (9.1 vs. 8.9, p = 0.001). The TyG index was a significant predictor of GDM (p < 0.05), with each one-unit increase associated with significantly higher odds of GDM (OR = 12.29), after adjusting for covariates. ROC analysis demonstrated an AUC of 0.716 (95% CI: 0.627–0.793, p < 0.001) for the TyG index, and the optimal cut-off value was identified as 9.35, yielding a sensitivity of 38.5% and a specificity of 96.5% and a negative predictive value of 83.7%. Subgroup analyses indicated that the TyG index had limited discriminative ability for predicting GDM in both the post-load and insulin-requiring groups. Among conventional lipid ratios, TG/HDL demonstrated the highest predictive performance (AUC = 0.587), while LDL/HDL (AUC = 0.483) and TC/HDL (AUC = 0.509) demonstrated low predictive accuracy. Compared with conventional lipid ratios, the TyG index demonstrated superior predictive performance. Conclusions: A higher TyG index was positively associated with the development of GDM and showed better predictive ability than conventional lipid ratios. However, its low sensitivity limits its use as a standalone diagnostic tool, suggesting it may be most useful when combined with other clinical parameters. Full article

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

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16 pages, 2314 KB

Open AccessArticle

Placental Pathological Findings and Clinical Outcomes in Triplet Pregnancies Conceived via Oocyte Donation and Non-Oocyte Donation: A Case–Control Study

by Eva Manuela Pena-Burgos, Maria De la Calle, Jose Juan Pozo-Kreilinger, Cecilia García-Díaz and Rita María Regojo-Zapata

Diagnostics 2025, 15(21), 2681; https://doi.org/10.3390/diagnostics15212681 - 23 Oct 2025

Abstract

Objective: This study aimed to assess whether oocyte donation in triplet pregnancies is associated with increased risk of placental abnormalities and pregnancy complications compared to triplet pregnancies conceived through assisted reproductive technology (ART) without oocyte donation. Methods: This single-center, retrospective, case–control [...] Read more.

Objective: This study aimed to assess whether oocyte donation in triplet pregnancies is associated with increased risk of placental abnormalities and pregnancy complications compared to triplet pregnancies conceived through assisted reproductive technology (ART) without oocyte donation. Methods: This single-center, retrospective, case–control study analyzed triplet pregnancies conceived via ART. The case group included pregnancies resulting from oocyte donation, while the control group comprised triplet pregnancies conceived by ART without oocyte donation. Maternal, obstetric, fetal, and neonatal outcomes were assessed. Gross and histopathological placental findings were evaluated using standardized criteria. Univariate and multivariate statistical analyses were performed. Results: A total of 77 triplet pregnancies (231 fetuses) were included: 29 in the oocyte donation group (87 fetuses) and 48 in the non-oocyte donation group (144 fetuses). Multivariate analysis revealed significantly higher rates of pregnancy-induced hypertension (p = 0.03), preeclampsia (p = 0.03), fetal growth restriction (p = 0.04), and fetal death (p = 0.01) in the oocyte donation group. Placental evaluation showed a higher frequency of infarcts (p = 0.04) and chronic inflammatory lesions—chronic villitis (p = 0.02) and chronic deciduitis (p = 0.03)—as well as signs of fetal vascular malperfusion, including avascular villi (p = 0.02) and stromal–vascular karyorrhexis (p = 0.01). Intervillous fibrin deposition was also more common in this group (p = 0.02). Conclusions: Oocyte donation in triplet pregnancies is associated with increased rates of placental abnormalities and adverse maternal and fetal outcomes when compared with ART without oocyte donation. Placental examination may provide valuable insights into the mechanisms involved. Further research is warranted to clarify the underlying immunological and vascular pathways. Synopsis: In our cohort of 77 triplet pregnancies, those conceived via oocyte donation showed significantly higher rates of preeclampsia, fetal growth restriction, and fetal death. Placental examination revealed more chronic villitis, deciduitis, intervillous fibrin, avascular villi, and stromal–vascular karyorrhexis, suggesting immune and vascular dysfunction in oocyte donation pregnancies. Full article

(This article belongs to the Special Issue Hot Topics in Modern and Personalized Pathology)

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13 pages, 2814 KB

Open AccessArticle

Intratumoral SPP1⁺BCL2A1⁺ Tumor-Associated Macrophages Predict Poor Response to PD1 Blockade

by Chun-Hao Lai, Yu-Ping Hung, Po-Chun Tseng, Rahmat Dani Satria and Chiou-Feng Lin

Diagnostics 2025, 15(21), 2680; https://doi.org/10.3390/diagnostics15212680 - 23 Oct 2025

Abstract

Background/Objectives: Immune checkpoint blockade (ICB) has emerged as a promising therapeutic option for hepatocellular carcinoma (HCC), yet reliable biomarkers to predict clinical outcomes remain limited. Tumor-associated macrophages (TAMs) are increasingly recognized as key regulators of the tumor immune microenvironment. Methods: We interrogated a [...] Read more.

Background/Objectives: Immune checkpoint blockade (ICB) has emerged as a promising therapeutic option for hepatocellular carcinoma (HCC), yet reliable biomarkers to predict clinical outcomes remain limited. Tumor-associated macrophages (TAMs) are increasingly recognized as key regulators of the tumor immune microenvironment. Methods: We interrogated a publicly available HCC single-cell RNA sequencing (scRNA-seq) dataset to characterize intratumoral immune cell subpopulations. Through unsupervised clustering and gene signature analysis, we identified a distinct subset of SPP1 (secreted phosphoprotein 1, also known as osteopontin) and BCL2A1 (Bcl-2-related protein A1) double-positive TAMs. Their abundance was quantified and associated with patient outcomes. Further independent HCC transcriptomic datasets with annotated PD1-based ICB response status were used for examination. Results: Across the discovery (GSE149614; n = 10) cohort, elevated expression of intratumoral SPP1⁺BCL2A1⁺ TAMs was identified in HCC. In the ICB datasets (GSE151530; n = 4), patients with high SPP1⁺BCL2A1⁺ TAM expression further exhibited significantly poorer responses to ICB therapy. Further, the validation cohort (GSE206325; n = 18) confirmed these findings accordingly. Notably, these TAMs were expressed thoroughly within the immunosuppressive T-cell microenvironment in non-responders but were distinctly expressed among the cytotoxic T-cell responses in responders. Conclusions: Our findings identify SPP1⁺BCL2A1⁺ TAMs as a poor prognostic biomarker in HCC patients undergoing ICB therapy. By promoting an immunosuppressive microenvironment, SPP1⁺BCL2A1⁺ TAMs, which are survival-advantaged, may represent both a predictive marker and a potential therapeutic target to enhance the efficacy of immunotherapy. Full article

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

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13 pages, 2506 KB

Open AccessArticle

Spatial Distribution of Senescent Cells and Their Proximity to Immune Subsets in the Human Endometrium During the Implantation Window

by Dimitar Parvanov, Rumiana Ganeva, Margarita Ruseva, Maria Handzhiyska, Jinahn Safir, Lachezar Jelezarsky, Nina Vidolova, Dimitar Metodiev, Georgi Stamenov and Savina Hadjidekova

Diagnostics 2025, 15(21), 2679; https://doi.org/10.3390/diagnostics15212679 - 23 Oct 2025

Abstract

Background/Objectives: Senescent cells contribute to endometrial remodeling during the implantation window, but their spatial organization within the stroma remains poorly understood. This study aimed to characterize the distribution of senescent (p16-positive) cells in the functional layer of the endometrium and to evaluate [...] Read more.

Background/Objectives: Senescent cells contribute to endometrial remodeling during the implantation window, but their spatial organization within the stroma remains poorly understood. This study aimed to characterize the distribution of senescent (p16-positive) cells in the functional layer of the endometrium and to evaluate their spatial relationships with immune cell subsets. Methods: Endometrial biopsies from 68 women undergoing IVF were collected during the mid-luteal phase (LH+7, corresponding to the implantation window). Samples were analyzed by immunohistochemistry for p16 and immune markers (CD3, CD4, CD8, CD14, CD68, CD56, CD79α). Images from adjacent serial sections were digitally aligned, and senescent cell density, clustering, and nearest-neighbor distances to immune cells were quantified using HALO Image Analysis software (v3.4). Ratios of senescent-to-immune cell abundance were also calculated to account for stromal variability. Results: Senescent cells were heterogeneously dispersed within the stroma, with occasional high-density clusters. Quantitative analysis revealed that their abundance was lower than that of monocytes, macrophages, and total T cells, but higher than that of T-helper and B cells. Across patients, median senescent-to-immune cell ratios were approximately 1, indicating comparable abundances, except for CD4⁺ and CD79α⁺ subsets, where ratios were significantly elevated. Nearest-neighbor analysis showed that macrophages and monocytes localized in closest proximity to senescent cells (45 ± 20 μm and 45 ± 25 μm), while T-helper and NK cells were positioned at greater distances from senescent cells (102 ± 42 μm and 53 ± 23 μm, respectively). B cells showed the greatest separation (211 ± 66 μm). Correlation analysis confirmed density-driven proximity for most immune subsets, with CD4⁺ and CD56⁺ cells as exceptions, displaying limited spatial association with senescent cells. Conclusions: Senescent cells in the endometrium during the implantation window display heterogeneous distribution and selective spatial associations with immune subsets. Their preferential distancing from T-helper and NK cells suggests impaired local immune–senescence crosstalk, highlighting spatial profiling of senescent cells as a potential diagnostic marker of endometrial receptivity. Full article

(This article belongs to the Topic Development of Diagnosis and Treatment Modalities in Obstetrics and Gynecology)

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21 pages, 2910 KB

Open AccessCase Report

Perforator-Sparing Microsurgical Clipping of Tandem Dominant-Hemisphere Middle Cerebral Artery Aneurysms: Geometry-Guided Reconstruction of a Wide-Neck Bifurcation and Dorsal M1 Fusiform Lesion

by Matei Șerban, Corneliu Toader and Răzvan-Adrian Covache-Busuioc

Diagnostics 2025, 15(21), 2678; https://doi.org/10.3390/diagnostics15212678 - 23 Oct 2025

Abstract

Background and Clinical Significance: Tandem pathology at the dominant-hemisphere middle cerebral artery (MCA)—combining a wide-neck bifurcation aneurysm that shares the neck with both M2 origins and a short dorsal M1 fusiform dilation embedded in the lenticulostriate belt—compresses the therapeutic margin and complicates device-first [...] Read more.

Background and Clinical Significance: Tandem pathology at the dominant-hemisphere middle cerebral artery (MCA)—combining a wide-neck bifurcation aneurysm that shares the neck with both M2 origins and a short dorsal M1 fusiform dilation embedded in the lenticulostriate belt—compresses the therapeutic margin and complicates device-first pathways. We aimed to describe an anatomy-led, microscope-only sequence designed to secure an immediate branch-definitive result at the fork and to remodel dorsal M1 without perforator compromise, and to place these decisions within a pragmatic perioperative framework. Case Presentation: A 37-year-old right-handed man with reproducible, load-sensitive cortical association and capsulostriate signs underwent high-fidelity digital subtraction angiography (DSA) with 3D rotational reconstructions. Through a left pterional approach, vein-respecting Sylvian dissection achieved gravity relaxation. Reconstruction proceeded in sequence: a fenestrated straight clip across the bifurcation neck with the superior M2 encircled to preserve both M2 ostia, followed by a short longitudinal clip parallel to M1 to reshape the fusiform segment while keeping each lenticulostriate mouth visible and free. Temporary occlusion windows were brief (bifurcation 2 min 30 s; M1 < 2 min). No neuronavigation, intraoperative fluorescence, micro-Doppler, or intraoperative angiography was used. No perioperative antiplatelets or systemic anticoagulation were administered and venous thromboembolism prophylaxis followed institutional practice. The bifurcation dome collapsed immediately with round, mobile M2 orifices, and dorsal M1 regained near-cylindrical geometry with patent perforator ostia under direct inspection. Emergence was neurologically intact, headaches abated, and preoperative micro-asymmetries resolved without new deficits. The early course was uncomplicated. Non-contrast CT at three months showed structurally preserved dominant-hemisphere parenchyma without infarction or hemorrhage. Lumen confirmation was scheduled at 12 months. Conclusions: In dominant-hemisphere tandem MCA disease, staged, perforator-sparing clip reconstruction can restore physiologic branch and perforator behavior while avoiding prolonged antiplatelet exposure and device-related branch uncertainty. A future-facing pathway pairs subtle clinical latency metrics with high-fidelity angiography, reports outcomes in branch- and perforator-centric terms, and, where available, incorporates patient-specific hemodynamic simulation and noninvasive lumen surveillance to guide timing, technique, and follow-up. Full article

(This article belongs to the Special Issue Cerebrovascular Lesions: Diagnosis and Management, 2nd Edition)

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16 pages, 1513 KB

Open AccessArticle

Clinical Value of Galectin-9, Soluble TREM-1, and Soluble CD25 Among Critically Ill Patients with Organ Failure in the Emergency Department: A Prospective Observational Study

by Uihwan Kim, Sijin Lee, Kap Su Han, Su Jin Kim, Sungwoo Lee, Dae Won Park and Juhyun Song

Diagnostics 2025, 15(21), 2677; https://doi.org/10.3390/diagnostics15212677 - 23 Oct 2025

Abstract

Background/Objectives: This study investigated clinical value of galectin-9 (Gal-9), a soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), and soluble CD25 (sCD25) among critically ill patients with organ failure in the emergency department. Methods: Overall, 786 patients were enrolled and classified [...] Read more.

Background/Objectives: This study investigated clinical value of galectin-9 (Gal-9), a soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), and soluble CD25 (sCD25) among critically ill patients with organ failure in the emergency department. Methods: Overall, 786 patients were enrolled and classified into non-infectious organ failure (NIOF, n = 331), sepsis (n = 266), and septic shock (n = 189). The diagnostic value of Gal-9, sTREM-1, and sCD25 were evaluated by receiver operating characteristic curve analysis. The prognostic value of the biomarkers was evaluated using Kaplan–Meier survival curve and Cox proportional hazard model analyses. Results: Gal-9, sTREM-1, and sCD25 could discriminate sepsis from NIOF (Gal-9, area under the curve [AUC], 0.599–0.678; sTREM-1, AUC, 0.616–0.695; sCD25, AUC, 0.710–0.781) and septic shock from sepsis (Gal-9, AUC, 0.562–0.667; sTREM-1, AUC, 0.572–0.676; sCD25, AUC, 0.555–0.660), respectively. Sepsis patients with higher levels of biomarkers over their cut-off value showed higher 30-day mortality compared to those with lower levels below the cut-off value (Gal-9 ≥ 14,391.80 ng/L, p < 0.001; sTREM-1 ≥ 580.62 ng/L, p < 0.001; sCD25 ≥ 1639.29 ng/L, p < 0.001; respectively) (log-rank test). sCD25 is an independent risk factor for 30-day mortality in patients with sepsis or septic shock. Conclusions: Gal-9, sTREM-1, and sCD25 showed diagnostic and prognostic value in critically ill patients with organ failure. sCD25 can predict the 30-day mortality in patients with sepsis. Gal-9, sTREM-1, and sCD25 could serve as auxiliary biomarkers to support clinicians in effective sepsis management. Full article

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

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Diagnostics, Volume 15, Issue 21 (November-1 2025) – 43 articles

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