Diagnostics

14 pages, 2044 KB

Open AccessArticle

Molecular Characterization of Wilson’s Disease in Liver Transplant Patients: A Five-Year Single-Center Experience in Iran

by Zahra Beyzaei, Melika Majed, Seyed Mohsen Dehghani, Mohammad Hadi Imanieh, Ali Khazaee, Bita Geramizadeh and Ralf Weiskirchen

Diagnostics 2025, 15(19), 2504; https://doi.org/10.3390/diagnostics15192504 - 1 Oct 2025

Abstract

Background/Objectives: Wilson’s disease (WD) is an autosomal recessive disorder characterized by pathological copper accumulation, primarily in the liver and brain. Severe hepatic involvement can be effectively treated with liver transplantation (LT). Geographic variation in ATP7B mutations suggests the presence of regional patterns [...] Read more.

Background/Objectives: Wilson’s disease (WD) is an autosomal recessive disorder characterized by pathological copper accumulation, primarily in the liver and brain. Severe hepatic involvement can be effectively treated with liver transplantation (LT). Geographic variation in ATP7B mutations suggests the presence of regional patterns that may impact disease presentation and management. This study aims to investigate the genetic basis of WD in patients from a major LT center in Iran. Methods: A retrospective analysis was conducted on clinical, biochemical, and pathological data from patients suspected of WD who underwent evaluation for LT between May 2020 and June 2025 at Shiraz University of Medical Sciences. Genetic testing was carried out on 20 patients at the Shiraz Transplant Research Center (STRC). Direct mutation analysis of ATP7B was performed for all patients, and the results correlated with clinical and demographic information. Results: In total, 20 WD patients who underwent liver transplantation (15 males, 5 females) carried 25 pathogenic or likely pathogenic ATP7B variants, 21 of which were previously unreported. Fifteen patients were homozygous, and five were compound-heterozygous; all heterozygous combinations occurred in the offspring of second-degree consanguineous unions. Recurrent changes included p.L549V, p.V872E, and p.P992S/L, while two nonsense variants (p.E1293X, p.R1319X) predicted truncated proteins. Variants were distributed across copper-binding, transmembrane, phosphorylation, and ATP-binding domains, and in silico AlphaMissense scores indicate damaging effects for most novel substitutions. Post-LT follow-up showed biochemical normalization in the majority of recipients, with five deaths recorded during the study period. Conclusions: This single-center Iranian study reveals a highly heterogeneous ATP7B mutational landscape with a large proportion of novel population-specific variants and underscores the benefit of comprehensive gene sequencing for timely WD diagnosis and family counseling, particularly in regions with prevalent consanguinity. Full article

(This article belongs to the Special Issue Advanced Pathology and Diagnostics in Gastroenterology and Liver Diseases 2025)

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7 pages, 6824 KB

Open AccessInteresting Images

Infrequent, but Not Intricate Radiological and Pathological Diagnosis of Chronic Intestinal Pseudo-Obstruction—Presented in a Two Pediatrics Cases of the Visceral Myopathy

by Monika Kujdowicz, Grażyna Drabik, Damian Młynarski, Katarzyna Jędrzejowska, Wojciech Górecki, Anna Wierdak, Kamila Płachno and Józef Kobos

Diagnostics 2025, 15(19), 2503; https://doi.org/10.3390/diagnostics15192503 - 1 Oct 2025

Abstract

Obstruction differential diagnosis involves tumors, “acute abdomen”, and chronic pseudo-obstruction (CIPO). Pediatric CIPO cases have different backgrounds than adults’ and impairs development. The cases are rare; diagnosis and treatment are still not well established. Diagnosis is complex; clinical, radiological, molecular, and manometric pathologic [...] Read more.

Obstruction differential diagnosis involves tumors, “acute abdomen”, and chronic pseudo-obstruction (CIPO). Pediatric CIPO cases have different backgrounds than adults’ and impairs development. The cases are rare; diagnosis and treatment are still not well established. Diagnosis is complex; clinical, radiological, molecular, and manometric pathologic data are essential. The performance of broad radiological investigations and manometry is cumbersome in a small intestine. Herein, we present cases of a 14-year-old girl and 11-year-old boy with visceral myopathies (VMs). Presented cases show unique hardship in the analysis of standing and contrast bedside X-ray images—the colon distension alone speaks to Hirschsprung, and the clinicians could not confirm suspected short-segment disease for a long time. VMs are usually diagnosed up to 12 months of life and accompanied by other organ dysfunctions, which are herein absent. The key features here were also the involvement of the small intestine, lack of distant colon contraction, and for the long-lasting case in the boy, loss of haustration. The initial diagnosis relied on clinical data (vomiting, malabsorption, >6-month obstruction, and uncharacteristic biochemical tests), radiology (lack of tumor, enlargement of diameter, and fluid in small and large intestines), and manometry (presence of propagation wave and of anal inhibitory reflex in recto–anal manometry). Examination of intestinal muscle biopsies involved hematoxylin-eosin, trichrome-Masson staining, and immunohistochemistry. The characteristics were fibrosis, small vacuoles, muscle layer thinning, and decreased expression of smooth muscle actin and desmin. The localization of biopsies was chosen after X-ray examination, due to interruption and with various degree changes. The final diagnosis was put forward after the analysis of all accessible data. The diagnosis of VM underlines the importance of interdisciplinary co-work. An earlier intestine muscle biopsy and well-designed molecular panel might fasten the process of diagnosis. Deeper exploration of phenotype–genotype correlation of various VM presentations in the future is crucial for personalized treatment. Full article

(This article belongs to the Special Issue Pediatric Gastrointestinal Pathology)

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Graphical abstract

3 pages, 726 KB

Open AccessInteresting Images

Unilateral Vocal Cord Paralysis Diagnosed with Dynamic Digital Radiography

by Michaela Cellina

Diagnostics 2025, 15(19), 2502; https://doi.org/10.3390/diagnostics15192502 - 1 Oct 2025

Abstract

Flexible laryngoscopy (FL) is the standard diagnostic tool for vocal cord paralysis (VCP), but it involves patient discomfort, and its interpretation is subjective and operator-dependent. Dynamic digital radiography (DDR) is a novel imaging technique that acquires high-resolution sequential radiographs at a low radiation [...] Read more.

Flexible laryngoscopy (FL) is the standard diagnostic tool for vocal cord paralysis (VCP), but it involves patient discomfort, and its interpretation is subjective and operator-dependent. Dynamic digital radiography (DDR) is a novel imaging technique that acquires high-resolution sequential radiographs at a low radiation dose. While DDR has been widely applied in chest and diaphragmatic imaging, its use for laryngeal motion analysis has been poorly investigated. We present the case of a 50-year-old male referred for Computed Tomography (CT) of the neck and chest for suspected vocal cord paralysis. The referring physician did not specify the side of the suspected paralysis. Due to a language barrier and the absence of prior documentation, a detailed history could not be obtained. To assess vocal cord motion, we performed, for the first time in our Institution, a DDR study of the neck. During phonation maneuvers, DDR demonstrated fixation of the left vocal cord in an adducted paramedian position. CT confirmed this finding and did not highlight any further anomaly. This case demonstrates the feasibility of DDR as a low-cost, low-dose, non-invasive technique for functional evaluation of the larynx and may represent a valuable complementary imaging tool in laryngeal functional assessment. Full article

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

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12 pages, 570 KB

Open AccessArticle

Predictive Impact of Hematological and Biochemical Parameters on the Clinical Course of Sarcoidosis

by Tugba Onyilmaz, Serap Argun Baris, Huseyin Kaya, Ayse Zeynep Pehlivan, Hanife Albayrak, Sena Nur Aktoprak, Hasim Boyaci and Ilknur Basyigit

Diagnostics 2025, 15(19), 2501; https://doi.org/10.3390/diagnostics15192501 - 1 Oct 2025

Abstract

Background: Sarcoidosis is a systemic granulomatous disease with a highly variable clinical course, and distinguishing it from other diseases and predicting its prognosis can be challenging. In recent years, hematological and biochemical parameters have been investigated as potential biomarkers for assessing inflammation and [...] Read more.

Background: Sarcoidosis is a systemic granulomatous disease with a highly variable clinical course, and distinguishing it from other diseases and predicting its prognosis can be challenging. In recent years, hematological and biochemical parameters have been investigated as potential biomarkers for assessing inflammation and predicting disease prognosis. This study aimed to evaluate the prognostic value of the lactate dehydrogenase-to-albumin ratio (LAR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and lymphocyte-to-monocyte ratio (LMR). Methods: This retrospective, single-center study included 369 newly diagnosed patients with sarcoidosis who were admitted between January 2020 and October 2024. Sarcoidosis was diagnosed based on current ERS, ATS, and WASOG guidelines. At the 6-month follow-up, patients’ clinical courses were classified as regression, stable, or progression based on clinical, radiological, and pulmonary function tests. The predictive values of various hematological and biochemical parameters were analyzed using statistical methods, including binary logistic regression analysis and ROC analysis. Results: A total of 369 patients were included in the study. At the 6-month follow-up, 63.4% of patients showed regression, 21.4% had a stable course, and 15.2% showed progression. The progression group had a significantly higher LAR (5.26 [4.21–7.76]) compared to the stable/regression group (4.59 [3.82–5.86]) (p = 0.033). Additionally, baseline FVC% (OR, 0.97; p = 0.036) and the presence of dyspnea (OR, 3.08; p = 0.03) were identified as independent risk factors for disease progression. No significant associations were found between NLR, PLR, LMR, and serum ACE levels and the clinical course. The cutoff value of LAR for predicting disease progression was 4.87 (AUC: 0.605), with a sensitivity of 58.8% and specificity of 59.7%. Conclusions: Our study, which is the first to evaluate the prognostic value of LAR in sarcoidosis, identified this parameter as a significant indicator for the clinical course. The finding of significantly higher LAR levels in patients with disease progression suggests its potential as a prognostic biomarker. These results may help guide treatment and follow-up strategies, although further large-scale prospective studies are needed for validation. Full article

(This article belongs to the Special Issue Respiratory Diseases: Diagnosis and Management)

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14 pages, 1065 KB

Open AccessArticle

The Association Between Naples Prognostic Score and Coronary Collateral Circulation in Patients with Chronic Coronary Total Occlusion

by Abdullah Tunçez, Sevil Bütün, Kadri Murat Gürses, Hüseyin Tezcan, Aslıhan Merve Toprak Su, Burak Erdoğan, Mustafa Kırmızıgül, Muhammed Ulvi Yalçın, Yasin Özen, Kenan Demir, Nazif Aygül and Bülent Behlül Altunkeser

Diagnostics 2025, 15(19), 2500; https://doi.org/10.3390/diagnostics15192500 - 1 Oct 2025

Abstract

Background: Coronary collateral circulation (CCC) plays a crucial protective role in patients with chronic total occlusion (CTO), mitigating ischemia and improving long-term outcomes. However, the degree of collateral vessel development varies substantially among individuals. Systemic inflammatory and nutritional status may influence this variability. [...] Read more.

Background: Coronary collateral circulation (CCC) plays a crucial protective role in patients with chronic total occlusion (CTO), mitigating ischemia and improving long-term outcomes. However, the degree of collateral vessel development varies substantially among individuals. Systemic inflammatory and nutritional status may influence this variability. The Naples Prognostic Score (NPS) is a composite index reflecting these parameters, yet its relationship with CCC remains incompletely defined. Methods: We retrospectively analyzed 324 patients with angiographically confirmed CTO at Selçuk University Faculty of Medicine between 2014 and 2025. Coronary collaterals were graded using the Rentrop classification, and patients were categorized as having poor (grades 0–1) or good (grades 2–3) collaterals. The NPS was calculated using serum albumin, cholesterol, neutrophil-to-lymphocyte ratio, and lymphocyte-to-monocyte ratio. Baseline clinical and laboratory data were compared between groups. Univariate and multiple binary logistic regression analyses were performed to identify independent predictors of collateral development. Results: Of the 324 patients, 208 (64.2%) had poor and 116 (35.8%) had good collateral circulation. Patients with good collaterals had higher body mass index, HDL Cholesterol (HDL-C), and triglyceride levels, and significantly lower NPS values compared with those with poor collaterals (p < 0.05 for all). In multiple binary logistic regression analysis, HDL-C (OR 1.035; 95% CI 1.008–1.063; p = 0.011) and NPS (OR 0.226; 95% CI 0.130–0.393; p < 0.001) emerged as independent predictors of well-developed collaterals. Conclusions: Both NPS and HDL-C are independently associated with the degree of coronary collateral circulation in CTO patients. These findings highlight the interplay between systemic inflammation, nutritional status, lipid metabolism, and vascular adaptation. As simple and routinely available measures, NPS and HDL-C may serve as practical tools for risk stratification and identifying patients at risk of inadequate collateral formation. Prospective studies with functional assessments of collateral flow are warranted to confirm these associations and explore potential therapeutic interventions. Full article

(This article belongs to the Section Clinical Laboratory Medicine)

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12 pages, 1169 KB

Open AccessArticle

Demographic, Morphological, and Histopathological Characteristics of Melanoma and Nevi: Insights from Statistical Analysis and Machine Learning Models

by Blagjica Lazarova, Gordana Petrushevska, Zdenka Stojanovska and Stephen C. Mullins

Diagnostics 2025, 15(19), 2499; https://doi.org/10.3390/diagnostics15192499 - 1 Oct 2025

Abstract

Background: Early and accurate differentiation between melanomas and benign nevi is essential for making proper clinical decisions. This study aimed to identify clinical, morphological, and histopathological variables most strongly associated with melanoma, using both statistical and machine learning approaches. Methods: This study [...] Read more.

Background: Early and accurate differentiation between melanomas and benign nevi is essential for making proper clinical decisions. This study aimed to identify clinical, morphological, and histopathological variables most strongly associated with melanoma, using both statistical and machine learning approaches. Methods: This study evaluated 184 melanocytic lesions using clinical, morphological, and histopathological parameters. Univariable analyses were performed in XLStat statistical software, version 2014.5.03, while multivariable machine learning models were developed in Jamovi (version 2.4). Five supervised algorithms (random forest, partial least squares, elastic net regression, conditional inference trees, and k-nearest neighbors) were compared using repeated cross-validation, with performance evaluated by accuracy, Kappa, sensitivity, specificity, F1 score, and calibration. Results: Univariable analysis identified significant differences between melanomas and nevi in age, horizontal diameter, gender, lesion location, and selected histopathological features (cytological and extracellular matrix changes, epidermal interactions). However, several associations weakened in multivariable analysis due to collinearity and overlapping effects. Using glmnet, the most influential independent predictors were cytological changes, horizontal diameter, epidermal interactions, and extracellular matrix features, alongside age, gender, and lesion location. The model achieved high discrimination (AUC = 0.97, 95% CI: 0.93–0.99) and accuracy (training: 95.3%; test: 92.6%), confirming robustness. Conclusions: Structured demographic, morphological, and histopathological data—particularly age, lesion size, cytological and extracellular matrix changes, and epidermal interactions—can effectively support classification of melanocytic lesions. Machine learning approaches (the glmnet model in our study) provide a reliable framework to evaluate such predictors and offer practical diagnostic support in dermatopathology. Full article

(This article belongs to the Special Issue Artificial Intelligence in Dermatology)

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15 pages, 2453 KB

Open AccessArticle

Assessing REM Sleep as a Biomarker for Depression Using Consumer Wearables

by Roland Stretea, Zaki Milhem, Vadim Fîntînari, Cătălina Angela Crișan, Alexandru Stan, Dumitru Petreuș and Ioana Valentina Micluția

Diagnostics 2025, 15(19), 2498; https://doi.org/10.3390/diagnostics15192498 - 1 Oct 2025

Abstract

Background: Rapid-eye-movement (REM) sleep disinhibition—shorter REM latency and a larger nightly REM fraction—is a well-described laboratory correlate of major depression. Whether the same pattern can be captured efficiently with consumer wearables in everyday settings remains unclear. We therefore quantified REM latency and proportion [...] Read more.

Background: Rapid-eye-movement (REM) sleep disinhibition—shorter REM latency and a larger nightly REM fraction—is a well-described laboratory correlate of major depression. Whether the same pattern can be captured efficiently with consumer wearables in everyday settings remains unclear. We therefore quantified REM latency and proportion of REM sleep out of total sleep duration (labeled “REM sleep coefficient”) from Apple Watch recordings and examined their association with depressive symptoms. Methods: 191 adults wore an Apple Watch for 15 consecutive nights while a custom iOS app streamed raw accelerometry and heart-rate data. Sleep stages were scored with a neural-network model previously validated against polysomnography. REM latency and REM sleep coefficient were averaged per participant. Depressive severity was assessed twice with the Beck Depression Inventory and averaged. Descriptive statistics, normality tests, Spearman correlations, and ordinary-least-squares regressions were performed. Results: Mean ± SD values were BDI 13.52 ± 6.79, REM sleep coefficient 24.05 ± 6.52, and REM latency 103.63 ± 15.44 min. REM latency correlated negatively with BDI (Spearman ρ = −0.673, p < 0.001), whereas REM sleep coefficient correlated positively (ρ = 0.678, p < 0.001). Combined in a bivariate model, the two REM metrics explained 62% of variance in depressive severity. Conclusions: Wearable-derived REM latency and REM proportion jointly capture a large share of depressive-symptom variability, indicating their potential utility as accessible digital biomarkers. Larger longitudinal and interventional studies are needed to determine whether modifying REM architecture can alter the course of depression. Full article

(This article belongs to the Special Issue A New Era in Diagnosis: From Biomarkers to Artificial Intelligence)

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24 pages, 334 KB

Open AccessReview

From Heart to Abdominal Aorta: Integrating Multi-Modal Cardiac Imaging Derived Haemodynamic Biomarkers for Abdominal Aortic Aneurysm Risk Stratification, Surveillance, Pre-Operative Assessment and Therapeutic Decision-Making

by Rafic Ramses and Obiekezie Agu

Diagnostics 2025, 15(19), 2497; https://doi.org/10.3390/diagnostics15192497 - 1 Oct 2025

Abstract

Recent advances in cardiovascular imaging have revolutionized the assessment and management of abdominal aortic aneurysm (AAA) through the integration of sophisticated haemodynamic biomarkers. This comprehensive review evaluates the clinical utility and mechanistic significance of multiple biomarkers in AAA pathogenesis, progression, and treatment outcomes. [...] Read more.

Recent advances in cardiovascular imaging have revolutionized the assessment and management of abdominal aortic aneurysm (AAA) through the integration of sophisticated haemodynamic biomarkers. This comprehensive review evaluates the clinical utility and mechanistic significance of multiple biomarkers in AAA pathogenesis, progression, and treatment outcomes. Advanced cardiac imaging modalities, including four-dimensional magnetic resonance imaging (4D MRI), computational fluid dynamics (CFD), and specialized echocardiography, enable precise quantification of critical haemodynamic parameters. Wall shear stress (WSS) emerges as a fundamental biomarker, with values below 0.4 Pa indicating pathological conditions and increased risk for aneurysm progression. Time-averaged wall shear stress (TAWSS), typically maintaining values above 1.5 Pa in healthy arterial segments, provides crucial information about sustained haemodynamic forces affecting the vessel wall. The oscillatory shear index (OSI), ranging from 0 (unidirectional flow) to 0.5 (purely oscillatory flow), quantifies directional changes in WSS during cardiac cycles. In AAA, elevated OSI values between 0.3 and 0.4 correlate with disturbed flow patterns and accelerated disease progression. The relative residence time (RRT), combining TAWSS and OSI, identifies regions prone to thrombosis, with values exceeding 2–3 Pa⁻¹ indicating increased risk. The endothelial cell activation potential (ECAP), calculated as OSI/TAWSS, serves as an integrated metric for endothelial dysfunction risk, with values above 0.2–0.3 Pa⁻¹ suggesting increased inflammatory activity. Additional biomarkers include the volumetric perivascular characterization index (VPCI), which assesses vessel wall inflammation through perivascular tissue analysis, and pulse wave velocity (PWV), measuring arterial stiffness. Central aortic systolic pressure and the aortic augmentation index provide essential information about cardiovascular load and arterial compliance. Novel parameters such as particle residence time, flow stagnation, and recirculation zones offer detailed insights into local haemodynamics and potential complications. Implementation challenges include the need for specialized equipment, standardized protocols, and expertise in data interpretation. However, the potential for improved patient outcomes through more precise risk stratification and personalized treatment planning justifies continued development and validation of these advanced assessment tools. Full article

(This article belongs to the Special Issue Cardiovascular Diseases: Innovations in Diagnosis and Management)

12 pages, 1270 KB

Open AccessArticle

Transarterial Embolization for Refractory Non-Cervical-Origin Interscapular Pain Following Ultrasound-Guided Injection: A Retrospective Feasibility Study

by Yu-Han Huang, Chia-Wei Chang, Jui-Yuan Chen, Chia-Shiang Lin, Chun-Wei Lin, Ping-Sheng Lu, Neng-Yu Chiu and Keng-Wei Liang

Diagnostics 2025, 15(19), 2496; https://doi.org/10.3390/diagnostics15192496 - 1 Oct 2025

Abstract

Objective: Chronic non-cervical-origin interscapular pain remains challenging to treat when refractory to conservative management and ultrasound-guided injections. This retrospective feasibility study aimed to assess the feasibility, procedural practicality, safety, and preliminary clinical outcomes of transarterial embolization (TAE) as a salvage therapy in [...] Read more.

Objective: Chronic non-cervical-origin interscapular pain remains challenging to treat when refractory to conservative management and ultrasound-guided injections. This retrospective feasibility study aimed to assess the feasibility, procedural practicality, safety, and preliminary clinical outcomes of transarterial embolization (TAE) as a salvage therapy in this patient population. Methods: This single-center retrospective study included 20 patients with chronic interscapular pain (Numeric Rating Scale [NRS] score ≥5 for >3 months) who initially underwent ultrasound-guided injection therapy. Patients who experienced inadequate pain relief after 3 months (n = 10) proceeded to TAE, while the remaining 10 patients with sufficient relief formed the comparison group. TAE primarily targeted the transverse cervical artery using imipenem/cilastatin sodium as the embolic agent. Pain outcomes were assessed using NRS scores at 1, 3, and 6 months post-procedure. The primary outcome was pain reduction (≥50% decrease in NRS score), with secondary outcomes including technical success, medication use, and safety assessment. Results: The mean baseline NRS score for all patients was 6.5 ± 1.4, which decreased to 3.4 ± 2.0 at 1 month and 3.9 ± 2.5 at 3 months post-injection (p < 0.001). In the TAE group, the NRS score decreased from 7.4 ± 1.4 to 5.1 ± 1.1 at 1 month and 6.0 ± 1.4 at 3 months, indicating inadequate pain relief. In contrast, the injection-only group showed significant improvement, with NRS scores decreasing from 5.6 ± 0.5 to 1.6 ± 0.5 at 1 month and 1.7 ± 0.7 at 3 months (p < 0.001). The reduction in NRS scores was significantly less in the TAE group compared with the injection-only group (−2.2 vs. −4.0 and −28.7% vs. −71.4% at 1 month; −1.4 vs. −3.9 and −18.2% vs. −69.7% at 3 months; all p ≤ 0.001). Following TAE, the mean NRS score further decreased to 2.1 ± 0.7, 2.0 ± 1.1, and 1.9 ± 1.2 at 1, 3, and 6 months, respectively (p < 0.001), with clinical success rates of 90%, 100%, and 90% at these respective time points. At the final follow-up, the percentage of NRS score reduction was comparable between the TAE and injection-only groups (−74.8% vs. −69.7%, p = 0.397). No severe or life-threatening adverse events were observed; only self-limited adverse events were reported. Conclusions: In this retrospective feasibility study, TAE appeared safe and effective as a salvage therapy for patients with refractory non-cervical-origin interscapular pain unresponsive to injection therapy. Further prospective, randomized studies are needed to validate these findings, refine patient selection criteria, and optimize treatment outcomes. Full article

(This article belongs to the Special Issue Advances in Pain Medicine: Diagnosis and Management)

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13 pages, 482 KB

Open AccessReview

Echoes of Muscle Aging: The Emerging Role of Shear Wave Elastography in Sarcopenia Diagnosis

by Linda Galasso, Federica Vitale, Manuela Pietramale, Giorgio Esposto, Raffaele Borriello, Irene Mignini, Antonio Gasbarrini, Maria Elena Ainora and Maria Assunta Zocco

Diagnostics 2025, 15(19), 2495; https://doi.org/10.3390/diagnostics15192495 - 30 Sep 2025

Abstract

Sarcopenia, a progressive age-related loss of skeletal muscle mass, strength, and function, is a major contributor to disability, reduced quality of life, and mortality in older adults. While current diagnostic approaches, such as dual-energy X-ray absorptiometry (DXA), bioelectrical impedance analysis (BIA), magnetic resonance [...] Read more.

Sarcopenia, a progressive age-related loss of skeletal muscle mass, strength, and function, is a major contributor to disability, reduced quality of life, and mortality in older adults. While current diagnostic approaches, such as dual-energy X-ray absorptiometry (DXA), bioelectrical impedance analysis (BIA), magnetic resonance imaging (MRI), and computed tomography (CT), are widely used to assess muscle mass, they have limitations in detecting early qualitative changes in muscle architecture and composition. Shear Wave Elastography (SWE), an ultrasound-based technique that quantifies tissue stiffness, has emerged as a promising tool to evaluate both muscle quantity and quality in a non-invasive, portable, and reproducible manner. Studies suggest that SWE can detect alterations in muscle mechanical properties associated with sarcopenia, providing complementary information to traditional morphometric assessments. Preliminary evidence indicates its good reproducibility, feasibility in various clinical settings, and potential for integration into routine evaluations. This narrative review summarizes current evidence on the use of SWE for the assessment of sarcopenia across diverse populations. Full article

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

22 pages, 3227 KB

Open AccessArticle

Associations Between Regulatory Immune Cells, Thymus Cellular Remodeling, and Vascular Aging in Advanced Coronary Atherosclerosis: A Pilot Study

by Irina Kologrivova, Alexey Dmitriukov, Natalia Naryzhnaya, Olga Koshelskaya, Olga Kharitonova, Alexandra Vyrostkova, Elena Kravchenko, Ivan Stepanov, Sergey Andreev, Vladimir Evtushenko, Anna Gusakova, Oksana Ogurkova and Tatiana Suslova

Diagnostics 2025, 15(19), 2494; https://doi.org/10.3390/diagnostics15192494 - 30 Sep 2025

Abstract

Background/Objectives: Biological aging phenotypes in coronary artery disease (CAD) include coronary atherosclerosis, vascular aging, and endothelial dysfunction. The aim of the present study was to investigate the potential links between aging phenotypes, regulatory immune cells, and features of the thymus in patients with [...] Read more.

Background/Objectives: Biological aging phenotypes in coronary artery disease (CAD) include coronary atherosclerosis, vascular aging, and endothelial dysfunction. The aim of the present study was to investigate the potential links between aging phenotypes, regulatory immune cells, and features of the thymus in patients with CAD. Methods: A single-center, cross-sectional, comparative study was conducted. Patients were stratified according to the severity of coronary atherosclerosis: patients with a Gensini score ≥ 65 points and patients with a Gensini score < 65 points. Peripheral blood and thymus biopsy were obtained. Imaging flow cytometry, ELISA, and immunohistochemical analysis were used for analysis. Results: Thymic morphology ranged from total fatty involution to a preserved structure of the thymus (20–80% area in 31% of obtained samples) but was not associated with the severity of atherosclerosis. Meanwhile, patients with a Gensini score ≥ 65 had impaired thymus cellular composition compared to patients with a Gensini score < 65 points; increased frequency of CD8+ T lymphocytes and NK cells; and decreased frequency of CD4 + CD8+ T lymphocytes. In peripheral blood, the main determinants of a Gensini score ≥ 65 points were low absolute counts of eMDSCs and CD25^low Tregs with FoxP3 nuclear translocation, while advanced vascular aging was associated with elevated eMDSC absolute counts. Advanced coronary atherosclerosis was also associated with decreased numbers of endothelial progenitor cells in circulation. Conclusions: Thymus dysfunction accompanies CAD progression and is manifested in changes in cellular composition rather than morphology. In CAD patients, MDSC and Treg lymphocytes are equally involved in the progression of coronary atherosclerosis, which is aggravated by the decreased regulatory potential of the endothelium. Vascular aging represents a distinct phenotype of biological aging in CAD patients, characterized by the expansion of eMDSCs. Full article

(This article belongs to the Special Issue Molecular Diagnosis and Medical Management of Cardiovascular Diseases)

22 pages, 384 KB

Open AccessReview

Molecular Diagnostics and Personalized Therapeutics in Differentiated Thyroid Carcinoma: A Clinically Oriented Review

by Andrés Coca-Pelaz, Juan Pablo Rodrigo, Mark Zafereo, Iain Nixon, Pia Pace-Asciak, Gregory W. Randolph, Carlos Suárez and Alfio Ferlito

Diagnostics 2025, 15(19), 2493; https://doi.org/10.3390/diagnostics15192493 - 30 Sep 2025

Abstract

Differentiated thyroid carcinoma (DTC) is the most common endocrine malignancy and typically has a favorable prognosis. However, a subset of patients experience aggressive disease, recurrence, or treatment resistance, underscoring the need for more precise diagnostic and therapeutic strategies. Advances in molecular profiling have [...] Read more.

Differentiated thyroid carcinoma (DTC) is the most common endocrine malignancy and typically has a favorable prognosis. However, a subset of patients experience aggressive disease, recurrence, or treatment resistance, underscoring the need for more precise diagnostic and therapeutic strategies. Advances in molecular profiling have improved the management of thyroid cancer by enabling risk-adapted treatment and targeted interventions. This narrative review offers a clinically focused synthesis of the current role of molecular diagnostics and personalized therapeutics in DTC. We examine key genetic alterations and their diagnostic, prognostic, and therapeutic implications, and discuss how molecular markers enhance traditional risk stratification systems, informing surgical decisions, radioactive iodine (RAI) use, and surveillance. The growing role of targeted therapies, such as tyrosine kinase inhibitors and agents against specific oncogenic drivers, is reviewed, particularly for RAI-refractory DTC. We also address real-world challenges in implementing precision medicine, including access, cost, and standardization. Future directions, such as liquid biopsy, artificial intelligence, and multi-omic integration, are explored as tools to achieve fully personalized care. This review aims to bridge the gap between molecular discovery and clinical application, offering practical insights for endocrinologists, surgeons, oncologists, and multidisciplinary teams managing DTC. Full article

(This article belongs to the Special Issue Advances in Molecular Pathology and Imaging for Precision Diagnosis and Treatment of Tumors)

17 pages, 995 KB

Open AccessArticle

Assessment of Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancer: Interobserver Variability and Contributing Factors

by Nurkhairul Bariyah Baharun, Mohamed Afiq Hidayat Zailani, Afzan Adam, Qiaoyi Xu, Muaatamarulain Mustangin and Reena Rahayu Md Zin

Diagnostics 2025, 15(19), 2492; https://doi.org/10.3390/diagnostics15192492 - 30 Sep 2025

Abstract

Background/Objectives: Tumor-infiltrating lymphocytes (TILs) are emerging as a crucial prognostic biomarker in triple-negative breast cancer (TNBC). However, their clinical utility remains constrained by the subjectivity and interobserver variability of manual scoring, despite standardization efforts by the International TILs Working Group (TIL-WG). This study [...] Read more.

Background/Objectives: Tumor-infiltrating lymphocytes (TILs) are emerging as a crucial prognostic biomarker in triple-negative breast cancer (TNBC). However, their clinical utility remains constrained by the subjectivity and interobserver variability of manual scoring, despite standardization efforts by the International TILs Working Group (TIL-WG). This study aimed to evaluate the interobserver agreement among pathologists in scoring stromal and intratumoral TILs from H&E-stained TNBC slides and to identify contributing histological factors. Methods: Two consultant pathologists at Hospital Canselor Tuanku Muhriz, Kuala Lumpur, independently assessed 64 TNBC cases using TIL-WG guidelines. Interobserver agreement was quantified using the intraclass correlation coefficient (ICC) and Cohen’s kappa coefficient. Cases with over 10% scoring discrepancies underwent review by a third pathologist, and a consensus discussion was held to explore the underlying confounders. Results: Our results showed moderate interobserver agreement for stromal TILs (ICC = 0.58) and strong agreement for intratumoral TILs (ICC = 0.71). Significant variability was attributed to three main confounding variables: heterogeneous TIL distribution, poorly defined tumor-stroma interface, and focal dense lymphoid infiltrates. Conclusions: These findings highlight the need for standardized TIL scoring protocols and suggest that validated AI-based tools may help mitigate observer variability in future TIL assessments. Full article

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

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17 pages, 1744 KB

Open AccessArticle

Predicting Mortality in Older Adults Using Comprehensive Geriatric Assessment: A Comparative Study of Traditional Statistics and Machine Learning Approaches

by Esin Avsar Kucukkurt, Esra Tokur Sonuvar, Dilek Yapar, Yasemin Demir Avcı, Irem Tanriverdi, Andisha Behzad and Pinar Soysal

Diagnostics 2025, 15(19), 2491; https://doi.org/10.3390/diagnostics15192491 - 30 Sep 2025

Abstract

Objective: The objective was to evaluate the ability of Comprehensive Geriatric Assessment (CGA) parameters to predict all-cause mortality in older adults using both traditional statistical methods and machine learning (ML) approaches. Methods: A total of 1.974 older adults from a university hospital outpatient [...] Read more.

Objective: The objective was to evaluate the ability of Comprehensive Geriatric Assessment (CGA) parameters to predict all-cause mortality in older adults using both traditional statistical methods and machine learning (ML) approaches. Methods: A total of 1.974 older adults from a university hospital outpatient clinic were included in this study. Ninety-six CGA-related variables encompassing functional and nutritional status, frailty, mobility, cognition, mood, chronic conditions, and laboratory findings were assessed. Cox proportional hazards regression and six ML algorithms (logistic regression, support vector machine, decision tree, random forest, extreme gradient boosting, and artificial neural networks) were employed to identify mortality predictors. Model performance was evaluated using area under the curve (AUC), sensitivity, and F1-score. Results: During a median follow-up of 617 days (interquartile range [IQR]: 297–1015), 430 participants (21.7%) died. Lower Lawton instrumental activities of daily living scores, unintentional weight loss, slower gait speed, and elevated C-reactive protein levels were consistent mortality predictors across all models. The artificial neural network demonstrated the highest predictive performance (AUC = 0.970), followed by logistic regression (AUC = 0.851). SHapley Additive explanations (SHAP) analysis confirmed the relevance of these key features. Conclusions: CGA parameters provide robust prognostic information regarding mortality risk in older adults. Functional decline and inflammation markers offer greater predictive power than chronological age alone in assessing overall health and survival probability. Full article

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

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16 pages, 3259 KB

Open AccessArticle

Spinal Epidural Fat as an Imaging Biomarker of Visceral Obesity: An MRI-Based Quantitative Analysis

by Nicola Marrone, Gabriele Bilancia, Domenico Romeo, Valerio D’Agostino, Federico Ponti, Francesca Salamanna, Amandine Crombé and Paolo Spinnato

Diagnostics 2025, 15(19), 2490; https://doi.org/10.3390/diagnostics15192490 - 29 Sep 2025

Abstract

Background/Objectives: Spinal epidural lipomatosis (SEL) is increasingly recognized as a possible radiological indicator of Metabolic Syndrome (MS) and visceral adiposity. However, the precise relationship between visceral adiposity and the accumulation of epidural fat (EF) remains unclear. This study aimed to investigate the [...] Read more.

Background/Objectives: Spinal epidural lipomatosis (SEL) is increasingly recognized as a possible radiological indicator of Metabolic Syndrome (MS) and visceral adiposity. However, the precise relationship between visceral adiposity and the accumulation of epidural fat (EF) remains unclear. This study aimed to investigate the association between visceral adipose tissue (VAT) and EF thickness using quantitative MRI analyses. Methods: We retrospectively reviewed all MRI scans performed at our institution over a 7-month period, from May to November 2024. Two radiologists measured and recorded the VAT maximum antero-posterior diameter at the L3 level, EF maximum diameter at the L5-S1 level, spinal canal antero-posterior diameter at the L5-S1 level, and subcutaneous fat (SF) when included in the MRI images (at the L3 level) in all the MRI scans. Results: A cohort of 516 patients was collected (320 women and 196 men; mean age 57.31 ± 18.45 years old). In 508 patients (98.4%) SF and VAT were both measurable, while in 8 patients VAT only was assessable on MRI scans. Pearson correlation identified significant associations between EF and VAT thickness (correlation coefficient > 20%; p < 0.05). A linear regression model confirmed a significant, albeit modest, positive relationship between VAT and EF (R² = 5.4%). A multivariate regression model incorporating age, sex, spinal canal size, VAT, and SF improved the explanatory power (adjusted R² = 16.7%), with VAT, spinal canal diameter, and age emerging as significant predictors of EF (p < 0.001). Conclusions: Our study revealed in a large cohort of patients that EF and VAT are directly associated. On the other hand, SF resulted in not being associated with EF. These findings support the emerging concept that SEL can be a radiological phenotype of visceral obesity and, by extension, of MS. Integrating EF measurement into standard MRI interpretation may facilitate the early detection of SEL and offer additional insights into patients’ underlying metabolic profile. Full article

(This article belongs to the Special Issue Multimodal Imaging: Enhancing Precision Medicine Across Diverse Clinical Pathways)

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5 pages, 1212 KB

Open AccessInteresting Images

Squamous Metaplasia of Lactiferous Ducts (SMOLD) in a Male Patient: Clinical, Dermoscopic, and Histopathological Insights

by Beata Zagórska, Przemysław Miłosz, Jakub Żółkiewicz, Urszula Maińska and Martyna Sławińska

Diagnostics 2025, 15(19), 2489; https://doi.org/10.3390/diagnostics15192489 - 29 Sep 2025

Abstract

We present the case of a 44-year-old male patient who presented to a dermatology outpatient clinic due to an asymmetric swelling of the left nipple. The patient reported a burning sensation within the area, persisting for approximately six months. Due to the inconclusive [...] Read more.

We present the case of a 44-year-old male patient who presented to a dermatology outpatient clinic due to an asymmetric swelling of the left nipple. The patient reported a burning sensation within the area, persisting for approximately six months. Due to the inconclusive dermoscopic findings and lack of improvement following empirical treatment, a biopsy was performed. Histopathological examination revealed keratinizing squamous metaplasia of the lactiferous ducts (SMOLD). Full article

(This article belongs to the Special Issue Advances in Diagnosis and Management of Skin Diseases)

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8 pages, 1509 KB

Open AccessArticle

Neuroimaging Findings and Neurocognitive Features of Patients with Ochoa Syndrome (Urofacial Syndrome)—A Prospective Experimental Study

by Aykut Akinci, Murat Can Karaburun, Mehmet Fatih Ozkaya, Muhammed Arif Ibis, Tugba Babayigit, Merve Cikili Uytun, Elif Peker, Sena Unal, Seda Kaynak Sahap, Gozde Vatansever, Sertac Ustun, Tarkan Soygur and Berk Burgu

Diagnostics 2025, 15(19), 2488; https://doi.org/10.3390/diagnostics15192488 - 29 Sep 2025

Abstract

Background/Objectives: To characterize functional brain activation during smiling and to assess cognitive profiles in patients with Ochoa (Urofacial) syndrome (UFS). Materials and Methods: In a block-design fMRI paradigm, participants alternated between imitating a smiling emoji and viewing a fixation cross. Images were preprocessed [...] Read more.

Background/Objectives: To characterize functional brain activation during smiling and to assess cognitive profiles in patients with Ochoa (Urofacial) syndrome (UFS). Materials and Methods: In a block-design fMRI paradigm, participants alternated between imitating a smiling emoji and viewing a fixation cross. Images were preprocessed and analyzed in SPM12; Smile > Rest contrasts were tested with a voxelwise threshold of p < 0.001 (uncorrected). Cognitive levels were assessed using age-appropriate Wechsler scales administered by certified psychologists. Results: Six patients (mean age 20 years; 50% female) with genetically/clinically confirmed UFS were included. Smile > Rest elicited robust activation in the supplementary motor area (highest Z = 4.70), insula (largest cluster), dorsal anterior cingulate, primary motor cortex, and frontal eye fields, among others. Five patients completed cognitive testing; Full-Scale IQ ranged 50–74, consistent with mild intellectual disability to borderline intellectual functioning. Conclusions: During voluntary smiling, UFS patients exhibit activation patterns that overlap extensively with those reported in healthy cohorts. Nevertheless, cognitive performance was limited in this sample. Given the rarity of UFS and the small cohort, findings should be interpreted cautiously and validated in multicenter studies. Full article

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

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13 pages, 1673 KB

Open AccessArticle

Relationship Between Right Ventricular Function and Body Composition in Adolescents and Young Adults

by Karolina Angela Sieradzka Uchnar, Stefan Toth, Ingrid Schusterova, Dominik Pella, Silvia Gurbalova and Tibor Poruban

Diagnostics 2025, 15(19), 2487; https://doi.org/10.3390/diagnostics15192487 - 29 Sep 2025

Abstract

Objective: This study sought to examine the relationships between right ventricular (RV) parameters and function, and body composition in adolescents and young adult individuals with overweight and obesity. We hypothesized that abnormal body composition is linked to RV dysfunction and subclinical changes in [...] Read more.

Objective: This study sought to examine the relationships between right ventricular (RV) parameters and function, and body composition in adolescents and young adult individuals with overweight and obesity. We hypothesized that abnormal body composition is linked to RV dysfunction and subclinical changes in the ventricle. Methods: The study prospectively included 80 young adult individuals, with 55 being overweight or obese and 25 having a normal body weight. We examined differences in RV echocardiographic parameters between these groups and their relationship with body composition parameters. Results: Adolescents and young adults with overweight or obesity had greater RV pressure load, and larger RV diameter. Significant differences in RV size and strain were noted between groups. Across the cohort, lean body mass positively correlated with RV strain, while fat mass and total serum protein negatively correlated with RV strain (both p < 0.01 or lower). Conclusions: This study found that RV function and body composition are often linked and improving body composition could prevent RV dysfunction, while addressing wasting might enhance RV function. Overweight or obese young adults show decreased RV strain in the absolute value compared to those with normal body weight. Full article

(This article belongs to the Special Issue Echocardiography Applications in Cardiovascular Diseases)

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23 pages, 1668 KB

Open AccessArticle

Brain Stroke Classification Using CT Scans with Transformer-Based Models and Explainable AI

by Shomukh Qari and Maha A. Thafar

Diagnostics 2025, 15(19), 2486; https://doi.org/10.3390/diagnostics15192486 - 29 Sep 2025

Abstract

Background & Objective: Stroke remains a leading cause of mortality and long-term disability worldwide, demanding rapid and accurate diagnosis to improve patient outcomes. Computed tomography (CT) scans are widely used in emergency settings due to their speed, availability, and cost-effectiveness. This study proposes [...] Read more.

Background & Objective: Stroke remains a leading cause of mortality and long-term disability worldwide, demanding rapid and accurate diagnosis to improve patient outcomes. Computed tomography (CT) scans are widely used in emergency settings due to their speed, availability, and cost-effectiveness. This study proposes an artificial intelligence (AI)-based framework for multiclass stroke classification (ischemic, hemorrhagic, and no stroke) using CT scan images from the Ministry of Health of the Republic of Turkey. Methods: We adopted MaxViT, a state-of-the-art Vision Transformer (ViT)-based architecture, as the primary deep learning model for stroke classification. Additional transformer variants, including Vision Transformer (ViT), Transformer-in-Transformer (TNT), and ConvNeXt, were evaluated for comparison. To improve model generalization and handle class imbalance, classical data augmentation techniques were applied. Furthermore, explainable AI (XAI) was integrated using Grad-CAM++ to provide visual insights into model decisions. Results: The MaxViT model with augmentation achieved the highest performance, reaching an accuracy and F1-score of 98.00%, outperforming the baseline Vision Transformer and other evaluated models. Grad-CAM++ visualizations confirmed that the proposed framework effectively identified stroke-related regions, enhancing transparency and clinical trust. Conclusions: This research contributes to the development of a trustworthy AI-assisted diagnostic tool for stroke, facilitating its integration into clinical practice and improving access to timely and optimal stroke diagnosis in emergency departments. Full article

(This article belongs to the Special Issue 3rd Edition: AI/ML-Based Medical Image Processing and Analysis)

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