Diagnostics

29 pages, 722 KiB

Open AccessReview

Molecular Insights into Pleural Mesothelioma: Unveiling Pathogenic Mechanisms and Therapeutic Opportunities

by Teodora Zahiu, Carmen Mihaela Mihu, Bianca A. Bosca, Mariana Mărginean, Lavinia Patricia Mocan, Roxana-Adelina Ștefan, Rada Teodora Suflețel, Carina Mihu and Carmen Stanca Melincovici

Diagnostics 2025, 15(11), 1323; https://doi.org/10.3390/diagnostics15111323 (registering DOI) - 24 May 2025

Abstract

Pleural mesothelioma (PM) is a rare disease, which is going to be a global medical concern in the 21st century, because of its aggressiveness, late diagnosis, and insufficient therapies. This review seeks to enhance the comprehension of medical professionals regarding the risk factors [...] Read more.

Pleural mesothelioma (PM) is a rare disease, which is going to be a global medical concern in the 21st century, because of its aggressiveness, late diagnosis, and insufficient therapies. This review seeks to enhance the comprehension of medical professionals regarding the risk factors and environmental influences that contribute to the development of the disease, as well as its underlying mechanisms. In addition, we aim to provide a schematic yet thorough overview of diagnostic techniques in PM, emphasizing the significance of the immunohistochemical markers BAP1 and MTAP, with the latter serving as an almost ideal surrogate for the gold-standard diagnostic approach, FISH p16/CDKN2A deletion. The scientific world is grappling with BAP1, MTAP, and the tumour inflammatory microenvironment, because they are the key for personalized treatments and palliative care in this disease. Considering that the survival rate for patients with PM seldom surpasses five years, every moment is significant. Therefore, our article also highlights recent advancements in clinical assessments related to prognostic scoring and treatment options. PM is a complex disease, with gradual progression over decades, which requires further investigation covering the prevention, mutations, diagnosis and treatment. Full article

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

18 pages, 2879 KiB

Open AccessArticle

PEBP1 and 15-LO-1 in Asthma: Biomarker Potential for Diagnosis and Severity Stratification

by Vijayalakshmi Vadde, Mohammed Kaleem Ullah, Mandya Venkateshmurthy Greeshma, Muhlisa Muhammed Ali Laila, Athira Nair, Sivasubramaniam Karunakaran, SubbaRao V. Madhunapantula, Sindaghatta Krishnarao Chaya, Komarla Sundararaja Lokesh, Jayaraj Biligere Siddaiah and Padukudru Anand Mahesh

Diagnostics 2025, 15(11), 1322; https://doi.org/10.3390/diagnostics15111322 (registering DOI) - 24 May 2025

Abstract

Background: Ferroptosis, a regulated form of cell death characterized by iron-dependent lipid peroxidation, has been implicated in the pathogenesis of asthma. The ferroptosis markers PEBP1 and 15-LO-1 are increasingly recognized as potential biomarkers for asthma. This study investigates the association of these markers [...] Read more.

Background: Ferroptosis, a regulated form of cell death characterized by iron-dependent lipid peroxidation, has been implicated in the pathogenesis of asthma. The ferroptosis markers PEBP1 and 15-LO-1 are increasingly recognized as potential biomarkers for asthma. This study investigates the association of these markers with asthma and its severity to evaluate their diagnostic potential. Methods: This cross-sectional study included 45 asthmatic patients and 45 healthy controls. Serum phosphatidylethanolamine-binding protein 1 (PEBP1) and 15-lipoxygenase-1 (15-LO-1) levels were measured using ELISA. Spirometric parameters (FEV₁, FEV₁/FVC ratio, and PEFR) were recorded. A multivariate regression assessed associations between ferroptosis markers and asthma severity. A generalized linear model (GLM) analyzed the relationship between biomarkers (PEBP1 and 15-LO-1) and lung function parameters. A receiver operating characteristic (ROC) analysis evaluated the discriminative capacity of PEBP1 and 15-LO-1. Results: PEBP1 and 15-LO-1 levels were significantly associated with asthma. The multivariate analysis revealed that low PEBP1 levels were strongly associated with asthma and severe asthma (p < 0.001). While elevated 15-LO-1 levels were associated with asthma (p < 0.001), they did not correlate with severity. The ROC analysis demonstrated excellent discriminative capacity for PEBP1 (AUC 0.962, cutoff 1509.8 pg/mL) and 15-LO-1 (AUC 0.895, cutoff 144.8 pg/mL). Lower PEBP1 and higher 15-LO-1 levels were associated with reduced lung function, and lower FEV₁, FEV₁/FVC, and PEF. Older age and female gender were associated with severe asthma. Conclusions: PEBP1 and 15-LO-1 are promising biomarkers for asthma, with PEBP1 showing strong correlations with asthma severity. These findings highlight the potential role of ferroptosis markers in asthma and underscore the need for further longitudinal studies to explore these markers’ clinical utility in personalized asthma management. Full article

(This article belongs to the Section Clinical Laboratory Medicine)

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11 pages, 1069 KiB

Open AccessArticle

Comparison of Cottle-Area-2 and Cottle-Area-3 in Computed Tomography Scans of Patients with Nasal Obstruction and Controls

by Helen Heppt, Gerlig Widmann, Matthias Santer, Felix Riechelmann, Herbert Riechelmann and Aris I. Giotakis

Diagnostics 2025, 15(11), 1321; https://doi.org/10.3390/diagnostics15111321 (registering DOI) - 24 May 2025

Abstract

Background/Objectives: Data that compare nasal Cottle-area-2 (i.e., nasal valve) and Cottle-area-3 are sparce. We intended to compare these areas in subjects with and without nasal obstruction. Methods: We compared cross-sectional areas, derived by computed tomography, of Cottle-area-2 (CT-CSA_COT-2) and [...] Read more.

Background/Objectives: Data that compare nasal Cottle-area-2 (i.e., nasal valve) and Cottle-area-3 are sparce. We intended to compare these areas in subjects with and without nasal obstruction. Methods: We compared cross-sectional areas, derived by computed tomography, of Cottle-area-2 (CT-CSA_COT-2) and Cottle-area-3 (CT-CSA_COT-3), in cases planned for surgery due to chronic nasal obstruction and controls with trauma not involving the head. In these cases, we investigated the correlation of the size of narrow and wide sides with active anterior rhinomanometry (AAR). Results: In 56 cases, CT-CSA_COT-2 were 15% smaller than CT-CSA_COT-3 (all p < 0.007). However, both were similarly large in 56 controls (all p > 0.2). Both narrow sides of the CT-CSA_COT-2 and CT-CSA_COT-3 were significantly smaller in cases (69 ± 23 mm² and 79 ± 28 mm², respectively) than in controls (91 ± 21 mm²; p < 0.001 and 93 ± 21 mm²; p = 0.004, respectively). However, only the size of the total nasal airway of CT-CSA_COT-2 was significantly smaller in cases (p < 0.001), not that of CT-CSA_COT-3 (p > 0.2). Correlations of AAR with CT were significant only on the narrow sides (all p < 0.037), but not on the wide sides (all p > 0.2). Conclusions: In contrast to Cottle-area-3, the total nasal airway of Cottle-area-2, i.e., nasal valve, was smaller in patients with nasal obstruction, the latter of which may not be easily identified before nasal surgical procedures. Full article

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

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15 pages, 2409 KiB

Open AccessArticle

Do LLMs Have ‘the Eye’ for MRI? Evaluating GPT-4o, Grok, and Gemini on Brain MRI Performance: First Evaluation of Grok in Medical Imaging and a Comparative Analysis

by Alperen Sozer, Mustafa Caglar Sahin, Batuhan Sozer, Gokberk Erol, Ozan Yavuz Tufek, Kerem Nernekli, Zuhal Demirtas and Emrah Celtikci

Diagnostics 2025, 15(11), 1320; https://doi.org/10.3390/diagnostics15111320 (registering DOI) - 24 May 2025

Abstract

Background/Objectives: Large language models (LLMs) are revolutionizing the world and the field of medicine while constantly improving themselves. With recent advancements in image interpretation, evaluating the reasoning capabilities of these models and benchmarking their performance on brain MRI tasks has become crucial, [...] Read more.

Background/Objectives: Large language models (LLMs) are revolutionizing the world and the field of medicine while constantly improving themselves. With recent advancements in image interpretation, evaluating the reasoning capabilities of these models and benchmarking their performance on brain MRI tasks has become crucial, as they may be utilized—albeit off-label—for patient care by both neurosurgeons and non-neurosurgeons. Methods: ChatGPT-4o, Grok, and Gemini were presented with 35,711 slices of brain MRI, including various pathologies and normal MRIs. Models were asked to identify the MRI sequence and determine the presence of pathology. Their individual performances were measured and compared with one another. Results: GPT refused to answer 28.02% of the slices despite three attempts, whereas Grok and Gemini provided responses on the first attempt for every slice. Gemini achieved 74.54% pathology prediction and 46.38% sequence prediction accuracy. GPT-4o achieved 74.33% pathology prediction and 85.98% sequence prediction accuracy for questions that it had answered (53.50% and 61.67% in total, respectively). Grok achieved 65.64% pathology prediction and 66.23% sequence prediction accuracy. Conclusions: The image interpretation capabilities of the investigated LLMs are limited for now and require further refinement before competing with specifically trained and fine-tuned dedicated applications. Amongst them, Gemini outperforms the others in pathology prediction while Grok outperforms others in sequence prediction. These limitations should be kept in mind if use during patient care is planned. Full article

(This article belongs to the Special Issue Artificial Intelligence in Neuroimaging 2024)

4 pages, 461 KiB

Open AccessInteresting Images

Platelet Satellitism in a Patient with Underlying Infection, Immune Thrombocytopenic Purpura (ITP) and Multiple Sclerosis

by Athanasios Liaskas, Natali El-Gkotmi, Anestis Karapaschalidis, Dimitrios Tzanetakos and Serena Valsami

Diagnostics 2025, 15(11), 1319; https://doi.org/10.3390/diagnostics15111319 (registering DOI) - 24 May 2025

Abstract

Platelet satellitism (PS) is an in vitro phenomenon of platelets adhering around white blood cells, especially in blood samples anticoagulated with K₃EDTA. This, in some cases, can lead to spurious thrombocytopenia, without platelet dysfunction or bleeding events. Diagnosis is made by [...] Read more.

Platelet satellitism (PS) is an in vitro phenomenon of platelets adhering around white blood cells, especially in blood samples anticoagulated with K₃EDTA. This, in some cases, can lead to spurious thrombocytopenia, without platelet dysfunction or bleeding events. Diagnosis is made by peripheral blood smear examination. The potential mechanism for PS remains largely unknown; however, it possibly involves the formation of IgG antibodies against the platelet glycoprotein receptor IIb/IIIa (GPIIb/IIIa). PS has been observed in various medical conditions, including infectious, autoimmune, and lymphoproliferative disorders, without an obvious causative relationship. Here, we describe a case of PS in a patient who presented with infection in the setting of underlying Immune Thombocytopenic Purpura and Multiple Sclerosis. Full article

(This article belongs to the Section Clinical Laboratory Medicine)

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24 pages, 3487 KiB

Open AccessArticle

A Convolutional Mixer-Based Deep Learning Network for Alzheimer’s Disease Classification from Structural Magnetic Resonance Imaging

by M. Krithika Alias Anbu Devi and K. Suganthi

Diagnostics 2025, 15(11), 1318; https://doi.org/10.3390/diagnostics15111318 - 23 May 2025

Abstract

Objective: Alzheimer’s disease (AD) is a neurodegenerative disorder that severely impairs cognitive function across various age groups, ranging from early to late sixties. It progresses from mild to severe stages, so an accurate diagnostic tool is necessary for effective intervention and treatment planning. [...] Read more.

Objective: Alzheimer’s disease (AD) is a neurodegenerative disorder that severely impairs cognitive function across various age groups, ranging from early to late sixties. It progresses from mild to severe stages, so an accurate diagnostic tool is necessary for effective intervention and treatment planning. Methods: This work proposes a novel AD classification architecture that integrates depthwise separable convolutional layers with traditional convolutional layers to efficiently extract features from structural magnetic resonance imaging (sMRI) scans. This model benefits from excellent feature extraction and lightweight operation, which reduces the number of parameters without compromising accuracy. The model learns from scratch with optimized weight initialization, resulting in faster convergence and improved generalization. However, medical imaging datasets contain class imbalance as a major challenge, which often results in biased models with poor generalization to the underrepresented disease stages. A hybrid sampling approach combining SMOTE (synthetic minority oversampling technique) with the ENN (edited nearest neighbors) effectively handles the complications of class imbalance issue inherent in the datasets. An explainable activation space occlusion sensitivity map (ASOP) pixel attribution method is employed to highlight the critical regions of input images that influence the classification decisions across different stages of AD. Results and Conclusions: The proposed model outperformed several state-of-the-art transfer learning architectures, including VGG19, DenseNet201, EfficientNetV2S, MobileNet, ResNet152, InceptionV3, and Xception. It achieves noteworthy results in disease stage classification, with an accuracy of 98.87%, an F1 score of 98.86%, a precision of 98.80%, and recall of 98.69%. These results demonstrate the effectiveness of the proposed model for classifying stages of AD progression. Full article

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

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16 pages, 440 KiB

Open AccessArticle

Lumbar Temperature Map of Elderly Individuals with Chronic Low Back Pain—An Infrared Thermographic Analysis

by Nelson Albuquerque, Liliana Gonçalves, Wally Strasse, Joaquim Gabriel, Laetitia Teixeira and Pedro Cantista

Diagnostics 2025, 15(11), 1317; https://doi.org/10.3390/diagnostics15111317 - 23 May 2025

Abstract

Background/Objectives: Chronic low back pain (CLBP) is a prevalent condition that significantly impacts the aging population. Among non-invasive assessment tools, infrared thermography (IRT) has been highlighted as a radiation-free method to evaluate thermal variations in the lumbar region. However, its applicability in [...] Read more.

Background/Objectives: Chronic low back pain (CLBP) is a prevalent condition that significantly impacts the aging population. Among non-invasive assessment tools, infrared thermography (IRT) has been highlighted as a radiation-free method to evaluate thermal variations in the lumbar region. However, its applicability in clinical practice and correlation with functional and pain-related parameters remain unclear. This study aimed to analyze the thermal profile of the lumbar region in elderly individuals with CLBP and explore potential correlations between lumbar temperature patterns and clinical factors such as pain intensity and functional capacity. Methods: A cross-sectional observational study was performed in an outpatient setting. The population included thirty-one elderly individuals diagnosed with CLBP. IRT was used to assess the lumbar temperature distribution, including participants who reported pain radiating to the lower limbs. Pain intensity was measured using a numerical rating scale (0–10). The functional assessments included spine mobility tests and validated questionnaires evaluating clinical characteristics. Results: No significant differences in lumbar temperature patterns were observed among the participants. Additionally, no correlation was found between pain intensity and functional capacity based on a thermographic analysis. Nonetheless, individuals reporting lower fatigue levels and those with a higher body mass index (BMI) were generally associated with cooler thermal readings on the lumbar region’s thermographic maps. Conclusions: These findings suggest that IRT may require methodological refinements, including optimized technical specifications and image acquisition protocols, to enhance its applicability in assessing CLBP. Indeed, IRT might not be the most effective tool for evaluating pain-related thermal changes in elderly populations. Further research is needed to clarify its role in clinical assessments. Full article

(This article belongs to the Special Issue Advanced Musculoskeletal Imaging in Clinical Diagnostics)

13 pages, 632 KiB

Open AccessArticle

The Association Between Serum Isthmin-1 and Disease Activity, Inflammation, and Autoantibody Status in Rheumatoid Arthritis

by Burak Oz, Ibrahım Gunduz, Gulsah Yamancan, Yusuf Dogan, Ramazan Fazıl Akkoc, Nevzat Gozel, Mustafa Gur, Ahmet Karatas and Suleyman Serdar Koca

Diagnostics 2025, 15(11), 1316; https://doi.org/10.3390/diagnostics15111316 - 23 May 2025

Abstract

Background/Objectives: Isthmin-1 (ISM1) is a secreted protein involved in immune regulation, inflammation, and angiogenesis. Although ISM1 has been implicated in chronic inflammatory conditions, its clinical relevance in rheumatoid arthritis (RA) remains unknown. This study aimed to evaluate serum ISM1 levels in RA [...] Read more.

Background/Objectives: Isthmin-1 (ISM1) is a secreted protein involved in immune regulation, inflammation, and angiogenesis. Although ISM1 has been implicated in chronic inflammatory conditions, its clinical relevance in rheumatoid arthritis (RA) remains unknown. This study aimed to evaluate serum ISM1 levels in RA patients and assess their associations with disease activity, autoantibody status, and inflammatory markers. Methods: This cross-sectional study included 90 RA patients fulfilling the 2010 ACR/EULAR criteria and 30 age- and sex-matched healthy controls. Serum ISM1 concentrations were measured using ELISA. Disease activity was assessed using DAS28-CRP and DAS28-ESR. Statistical analyses included group comparisons, correlation testing, multivariate linear regression, and ROC curve analysis to evaluate the predictive performance of ISM1 for remission or low disease activity. Results: Serum ISM1 levels were significantly lower in RA patients than in controls (454 ± 378 vs. 972 ± 809 ng/L, p < 0.001). ISM1 concentrations were inversely correlated with CRP, ESR, and both DAS28 indices. Multivariate regression confirmed independent associations between lower ISM1 concentrations and higher disease activity. ISM1 levels were significantly reduced in RF- and anti-CCP-positive patients, as well as in treatment-naïve early RA. ROC analysis identified a cut-off value of 673.73 ng/L for predicting remission or low disease activity, with an AUC of 0.713 (95% CI: 0.596–0.820), 100% specificity, and 38.9% sensitivity. Conclusions: This study is the first to demonstrate that serum ISM1 is independently associated with disease activity and autoantibody positivity in RA. High ISM1 levels may serve as a specific indicator of clinical remission or low disease activity, supporting its potential as a non-invasive biomarker for disease monitoring. Full article

(This article belongs to the Section Clinical Laboratory Medicine)

15 pages, 870 KiB

Open AccessSystematic Review

Artificial Intelligence in Rotator Cuff Tear Detection: A Systematic Review of MRI-Based Models

by Umile Giuseppe Longo, Benedetta Bandini, Letizia Mancini, Mario Merone, Emiliano Schena, Alessandro de Sire, Pieter D’Hooghe, Leandro Pecchia and Arianna Carnevale

Diagnostics 2025, 15(11), 1315; https://doi.org/10.3390/diagnostics15111315 - 23 May 2025

Abstract

Objective: This descriptive systematic review aimed to assess in the available literature on the current application and overall performance of Artificial Intelligence (AI) models in the diagnosis and classification of Rotator Cuff Tears (RCTs) using MRIs. Methods: The systematic review was [...] Read more.

Objective: This descriptive systematic review aimed to assess in the available literature on the current application and overall performance of Artificial Intelligence (AI) models in the diagnosis and classification of Rotator Cuff Tears (RCTs) using MRIs. Methods: The systematic review was performed by two of the authors from 2020 to November 2024. Only diagnostic studies involving AI application to MRI images of the rotator cuff were considered, including supraspinatus and biceps tears. Studies evaluating AI applications to Ultrasound or X-ray, or including only healthy rotator cuffs, were not analyzed in this paper. Results: The coronal plane in the T2 sequence emerged as the predominant imaging protocol, with the VGG network being the most widely utilized AI model. The studies included in this research exhibited a solid performance of the AI models with accuracy, ranging from 71.0% to 100%. The statistical analysis revealed no significant differences (p > 0.05) in accuracy, sensitivity, specificity, or precision between AI and human experts across studies that included such comparisons. Conclusions: While AI can significantly improve diagnostic efficiency and workflow optimization, future studies must focus on external validation, regulatory approval, and AI-human collaboration models to ensure safe and effective integration into orthopedic imaging. Full article

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

13 pages, 664 KiB

Open AccessArticle

Validation of Takotsubo Syndrome Scoring System

by Dana Deeb, Ranel Loutati, Louay Taha, Mohammad Karmi, Akiva Brin, Ofir Rabi, Nir Levi, Noam Fink, Pierre Sabouret, Mohammed Manassra, Abed Qadan, Motaz Amro, Benyamin Khalev, Michael Glikson and Elad Asher

Diagnostics 2025, 15(11), 1314; https://doi.org/10.3390/diagnostics15111314 - 23 May 2025

Abstract

Background: Takotsubo syndrome (TS) mimics acute coronary syndrome in 1% to 3% of patients presenting with chest pain, ECG changes and echocardiographic transient apical wall hypokinesia. Objectives: This study aimed to validate a previously developed scoring system on a larger cohort [...] Read more.

Background: Takotsubo syndrome (TS) mimics acute coronary syndrome in 1% to 3% of patients presenting with chest pain, ECG changes and echocardiographic transient apical wall hypokinesia. Objectives: This study aimed to validate a previously developed scoring system on a larger cohort size. Methods: Patients admitted to an intensive cardiovascular care unit were divided into three groups: (a) patients diagnosed with TS, (b) females with anterior MI, and (c) other all-comer STEMIs. A 10-point scoring system was used: stressful events (three points), female gender (two points), no history of diabetes mellitus (two points), estimated left ventricular ejection fraction (LVEF) ≤40% on admission echocardiography (one point), positive troponin on admission (one point), and no smoking (one point). A t-test was applied to the three study groups,sensitivity and specificity testing was performed using the ROC curve method. Results: A total of 1150 patients were included in our study: 54 with TS, 97 females with anterior MI and 999 other all-comer STEMIs. Patients in the TS group were predominantly females with a higher rate of stressful events prior to admission, lower rates of diabetes mellitus and smoking, and lower LVEF% systolic function compared to the STEMI cohort. In a multivariate logistic regression analysis, the average TS scoring system was significantly higher in the TS group compared with the anterior STEMI and all-comer STEMI groups (8.3 vs. 5.7 vs. 3.83, p < 0.001, respectively) with an AUC of 0.83 for TS score ≥8. Conclusions: The 10-point TS scoring system is an easy, reliable, and useful diagnostic tool that might help in distinguishing patients with TS and ACS. Full article

(This article belongs to the Special Issue Clinical Diagnosis and Management in Cardiology)

9 pages, 1624 KiB

Open AccessCase Report

Diagnostic Challenges of Thyrotropin-Secreting Hypophyseal Macroadenoma Associated with Papillary Thyroid Carcinoma: Case Report and Literature Review

by Juras Jocys, Romena Laukienė and Algirdas Edvardas Tamošiūnas

Diagnostics 2025, 15(11), 1313; https://doi.org/10.3390/diagnostics15111313 - 23 May 2025

Abstract

Background and Clinical Significance: The concurrent presence of a thyrotropin-secreting hypophyseal adenoma (TSHoma) with a thyroid malignancy, such as papillary thyroid carcinoma (PTC), is exceptionally rare and significantly complicates clinical diagnosis and management. This rare combination raises difficult decisions regarding the treatment [...] Read more.

Background and Clinical Significance: The concurrent presence of a thyrotropin-secreting hypophyseal adenoma (TSHoma) with a thyroid malignancy, such as papillary thyroid carcinoma (PTC), is exceptionally rare and significantly complicates clinical diagnosis and management. This rare combination raises difficult decisions regarding the treatment sequence and carries the risk of exacerbating either or both conditions. Case report: We present the case of a 59-year-old female patient exhibiting persistent hyperthyroid symptoms with unusually normal TSH levels despite elevated thyroid hormone concentrations. Initial diagnostic imaging revealed a hypophyseal macroadenoma and a diffuse nodular goiter. After the macroadenoma diagnosis, the patient initially refused surgical intervention, and subsequent dopamine agonist therapy proved ineffective. Eight years later, during a routine follow-up, a thyroid ultrasound revealed a diffuse nodular goiter classified as EU-TIRADS 5, and papillary thyroid carcinoma was confirmed through fine needle aspiration biopsy. A total thyroidectomy and subsequent radioactive iodine therapy were performed. However, persistently elevated postoperative TSH levels remained despite high-dose levothyroxine therapy. Due to the increased risk of malignancy recurrence associated with elevated TSH levels, the patient consented to macroadenoma surgery. A successful transsphenoidal macroadenomectomy stabilized the patient’s condition, allowing for the normalization of TSH levels. Conclusions: This case underscores the importance of accurate differential diagnosis and highlights the challenges in managing TSH levels in patients with coexisting thyroid malignancies. With there being no clear guidelines for managing the combination of these conditions, decisions regarding treatment priority should consider the patient’s preferences, the risk of malignancy recurrence or progression, neurological symptoms, and the aggressiveness of the thyroid tumor. Full article

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

14 pages, 1043 KiB

Open AccessArticle

Deep Learning-Based Aortic Diameter Measurement in Traumatic Hemorrhage Using Shallow Attention Network: A Path Forward

by Yoonjung Heo, Go-Eun Lee, Jungchan Cho and Sang-Il Choi

Diagnostics 2025, 15(11), 1312; https://doi.org/10.3390/diagnostics15111312 - 23 May 2025

Abstract

Background/Objectives: The accurate assessment of aortic diameter (AoD) is essential in managing patients with traumatic hemorrhage, particularly during interventions such as resuscitative endovascular balloon occlusion of the aorta (REBOA). Manual AoD measurements are time-consuming and subject to inter-observer variability. This study aimed to [...] Read more.

Background/Objectives: The accurate assessment of aortic diameter (AoD) is essential in managing patients with traumatic hemorrhage, particularly during interventions such as resuscitative endovascular balloon occlusion of the aorta (REBOA). Manual AoD measurements are time-consuming and subject to inter-observer variability. This study aimed to develop and validate a deep learning (DL) model for automated AoD measurement in trauma patients requiring massive transfusion. Methods: Abdominal CT scans from 300 adult patients were retrospectively analyzed. A Shallow Attention Network was trained on 444 manually annotated axial CT images to segment the aorta and measure its diameter. An ellipse-based calibration method was employed for enhanced measurement accuracy. Results: The model achieved a mean Dice coefficient of 0.865 and an intersection over union of 0.9988. After calibration, the mean discrepancy between predicted and ground truth diameters was 2.11 mm. The median diaphragmatic AoD was 22.59 mm (interquartile range: 20.18–24.74 mm). Conclusions: The proposed DL model with ellipse-based calibration demonstrated robust performance in automated AoD measurement and may facilitate timely planning of aortic interventions in trauma care. Full article

(This article belongs to the Special Issue Deep Learning in Medical and Biomedical Image Processing)

14 pages, 1137 KiB

Open AccessSystematic Review

Intraepidermal Nerve Fiber Density as an Indicator of Neuropathy Predisposition: A Systematic Review with Meta-Analysis

by Alexandros Samolis, Theodore Troupis, Constantinus Politis, Nikos Pantazis, George Triantafyllou, George Tsakotos, Thomas Tegos, Nikolaos Lazaridis, Konstantinos Natsis and Maria Piagkou

Diagnostics 2025, 15(11), 1311; https://doi.org/10.3390/diagnostics15111311 - 23 May 2025

Abstract

Background/Objectives: Skin spot biopsy is the gold standard for diagnosing small fiber neuropathy. A systematic approach to intraepidermal nerve fiber density (IENFD) was conducted to estimate its value precisely in healthy and neuropathic subjects, independent of the neuropathy disease. The findings will [...] Read more.

Background/Objectives: Skin spot biopsy is the gold standard for diagnosing small fiber neuropathy. A systematic approach to intraepidermal nerve fiber density (IENFD) was conducted to estimate its value precisely in healthy and neuropathic subjects, independent of the neuropathy disease. The findings will serve as a guidance model for IENFD as an indicator of neuropathy predisposition. It was also investigated how IENFD was influenced by age, gender, and neuropathy. Methods: A systematic search of PubMed, Web of Science, and ScienceDirect was conducted to identify clinical studies from 1997 to 2022 concerning IENFD in healthy and neuropathic adult populations. Data were retrieved from longitudinal cohort studies, including 5–188 healthy and 6–40 neuropathic patients. Multilevel meta-regression was employed to assess associations between the anatomical region, mean patient age, and male/female ratio with IENFD. This method accounted for correlations between multiple outcomes from the same survey, offering a more nuanced analysis than standard meta-regression. Results: In the healthy population, the estimated (95% CI) IENFD values (fibers/mm) were 21.4 (19.9, 22.9) in the thigh, 17.7 (15.3, 20.1) in the forearm, 12.9 (11.8, 14.0) in the distal leg, 11.3 (6.1, 16.5) in the fingers, and 6.5 (4.4, 8.6) in the toes. The corresponding estimates in the neuropathic population were 17.2 (15.2, 19.2) in the thigh, 6.3 (2.3, 10.2) in the forearm, 5.1 (3.8, 6.4) in the distal leg, and 2.0 (0.0, 5.7) in the toes. In a healthy population, IENFD decreased with aging by 1.35 fibers/mm every 5 years (p < 0.001). Gender dimorphism in IENFD existed, with females showing higher values in the distal leg (13.6–10.5) compared to males (9.3–7.2). Conclusions: The systematic study and meta-analysis integrate evidence of IENFD in skin biopsies. This analysis reconciles findings from various methodologies and populations over two decades. Meta-regression techniques address variability due to biopsy site, fixation protocols, immunohistochemical markers, and demographics. To reduce future study heterogeneity, using the thigh is advisable as it shows the least variability. Additionally, standardizing the biopsy site internationally will ensure comparability. These findings urge further investigation into IENFD changes in neurodegenerative diseases and whether IENFD can be a reliable prognostic marker for neuropathy diagnosis. Full article

(This article belongs to the Special Issue Clinical Anatomy and Diagnosis of Peripheral Nervous System)

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12 pages, 541 KiB

Open AccessArticle

Study of the MTHFR 677C>T Polymorphism in Children and Adolescents with Hashimoto’s Thyroiditis: An Original Case–Control Study

by Savvas Kolanis, Elisavet Georgiou, Eleni P. Kotanidou, Vasiliki Rengina Tsinopoulou, Evdoxia Sapountzi, Emmanouel Hatzipantelis, Liana Fidani and Assimina Galli-Tsinopoulou

Diagnostics 2025, 15(11), 1310; https://doi.org/10.3390/diagnostics15111310 - 23 May 2025

Abstract

Background/Objectives: Hashimoto’s thyroiditis (HT) is the most common cause of hypothyroidism during childhood and adolescence. Children and adolescents with HT have an increased susceptibility to the development of thyroid nodules and thyroid cancer. Among the genetic causes of thyroid cancer, the 677C>T [...] Read more.

Background/Objectives: Hashimoto’s thyroiditis (HT) is the most common cause of hypothyroidism during childhood and adolescence. Children and adolescents with HT have an increased susceptibility to the development of thyroid nodules and thyroid cancer. Among the genetic causes of thyroid cancer, the 677C>T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene is also reported. This study investigated for the first time the association between the 677C>T polymorphism (rs1801133) of the MTHFR gene and HT in children and adolescents. Methods: This case–control study included 130 children and adolescents with HT and 130 healthy controls. The 677C>T polymorphism of the MTHFR gene was studied in all participants with Restriction Fragment Length Polymorphism (RFLP) methodology for genetic variance analysis. Results: Children and adolescents with HT presented approximately 2.5 times more frequently the T allele sequences (CT and TT variants) and the T alleles in total for the 677C>T polymorphism of the MTHFR gene compared to the healthy population (OR: 2.56, CI: 1.53–4.21 and OR: 2.57, CI: 1.59–4.16, respectively). Children and adolescents with HT and T allele sequences (CT and TT variants) exhibited abnormal thyroglobulin antibodies (anti-TG) two times more frequently compared to those with the wild-type (CC) sequence in the same population (OR: 2.13, CI: 1.04–4.389). Conclusions: Children and adolescents with HT showed an increased frequency of T allele sequences (CT and TT variants) and total T alleles of the 677C>T polymorphism of the MTHFR gene compared to the healthy population. Full article

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

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15 pages, 893 KiB

Open AccessArticle

Nomogram-Based Prediction of Survival in Stage IV Nasopharyngeal Carcinoma: A Retrospective Single-Center Study

by Peng Yeh, Chih-Ming Chang, Li-Jen Liao, Chia-Yun Wu, Chen-Hsi Hsieh, Pei-Wei Shueng, Po-Wen Cheng and Wu-Chia Lo

Diagnostics 2025, 15(11), 1309; https://doi.org/10.3390/diagnostics15111309 - 23 May 2025

Abstract

Background/Objectives: To assess the pretreatment and posttreatment clinical factors associated with the rate of survival at 1, 3, and 5 years in stage IV nasopharyngeal carcinoma (NPC) patients. Methods: Clinicopathological characteristics of 61 Stage IV NPC patients diagnosed between 2008 and [...] Read more.

Background/Objectives: To assess the pretreatment and posttreatment clinical factors associated with the rate of survival at 1, 3, and 5 years in stage IV nasopharyngeal carcinoma (NPC) patients. Methods: Clinicopathological characteristics of 61 Stage IV NPC patients diagnosed between 2008 and 2022 in a single tertiary medical center were retrospectively reviewed. Univariate and multivariate analyses were performed to evaluate the prognostic factors associated with overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS). A nomogram was developed to forecast DSS. Results: The OS at 1-year, 3-year, and 5-year were 93%, 70%, and 57%, while the DSS at 1-year, 3-year, and 5-year were 93%, 73%, and 58%, whereas the DFS at 1-year, 3-year, and 5-year were 51%, 44%, and 41%, respectively. In multivariate analyses, posttreatment body mass index (BMI) < 21.6 kg/m² (hazard ratio [HR] 2.717, 95% confidence interval [CI] 1.248–5.917, p = 0.012) was an independent indicator for worsened OS. Posttreatment BMI < 21.6 kg/m² (HR 3.003, 95% CI 1.340–6.757, p = 0.008) and pretreatment systemic inflammation response index (SIRI) ≥ 125 (HR 2.841, 95% CI 1.256–6.429, p = 0.012) were independent indicators for worsened DSS. Posttreatment BMI < 21.6 kg/m² (HR 3.650, 95% CI 1.757–7.576, p = 0.001), change in BMI < −1.93 kg/m² (HR 3.731, 95% CI 1.642–8.475, p = 0.002), and pretreatment SIRI ≥ 125 (HR 3.541, 95% CI 1.717–7.304, p = 0.001) were independent indicators for worsened DFS. A nomogram was created to predict DSS using posttreatment BMI and pretreatment SIRI. Conclusions: Associations with survival were observed between posttreatment BMI and OS, DSS, and DFS; pretreatment SIRI and DSS/DFS; and changes in BMI and DFS among patients with stage IV NPC. The developed nomogram aids in survival prediction. Full article

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

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10 pages, 958 KiB

Open AccessArticle

Minimally Invasive Surgery Versus Conventional Neurosurgical Treatments for Patients with Subcortical Supratentorial Intracerebral Hemorrhage: A Nationwide Study of Real-World Data from 2016 to 2022

by Huanwen Chen, Matthew K. McIntyre, Mihir Khunte, Ajay Malhotra, Mohamed Labib, Marco Colasurdo and Dheeraj Gandhi

Diagnostics 2025, 15(11), 1308; https://doi.org/10.3390/diagnostics15111308 - 23 May 2025

Abstract

Background: Neurosurgical interventions are often indicated for patients with subcortical, supratentorial intracerebral hemorrhage (ICH); however, the optimal treatment modality is controversial. Whether minimally invasive surgery (MIS) may be superior to conventional craniotomy (CC) or decompressive craniectomy (DC) in real-world clinical practice is [...] Read more.

Background: Neurosurgical interventions are often indicated for patients with subcortical, supratentorial intracerebral hemorrhage (ICH); however, the optimal treatment modality is controversial. Whether minimally invasive surgery (MIS) may be superior to conventional craniotomy (CC) or decompressive craniectomy (DC) in real-world clinical practice is unknown. Methods: This was a retrospective cohort study of hospitalization data from the 2016–22 Nationwide Readmissions Database. International Classification of Diseases—10th edition (ICD-10) codes were used to identify patients with primary supratentorial subcortical ICH who underwent neurosurgical treatment. Patients with ICH in other brain compartments (other than intraventricular hemorrhage) were excluded. Coprimary outcomes were routine discharge to home without rehabilitation needs (excellent outcome) and in-hospital mortality. Outcomes were compared between MIS versus CC and MIS versus DC, with multivariable adjustments for patient demographics and comorbidities. Results: A total of 3829 patients were identified; 418 underwent MIS (10.9%), 2167 (56.6%) underwent CC, and 1244 (32.5%) underwent DC. Compared to CC patients, MIS patients were less likely female (p = 0.004) but otherwise had similar patient characteristics; compared to DC patients, MIS patients were older, less likely female, more likely to have mental status abnormalities, more likely to have underlying dementia, less likely to undergo external ventricular drainage, more likely to have vascular risk factors (hypertension, hyperlipidemia, diabetes), and less likely to have underlying coagulopathy (all p < 0.05). After multivariable adjustments, MIS patients had higher odds of excellent outcomes compared to CC (OR 1.99 [95%CI 1.06–3.30], p = 0.039), and similar odds compared to DC (OR 1.10 [95%CI 0.66–1.86], p = 0.73). In terms of in-hospital mortality, MIS had lower odds compared to DC (OR 0.63 [95%CI 0.41–0.96], p = 0.032) and similar odds compared to CC (OR 0.81 [95%CI 0.56–1.18], p = 0.26). Conclusions: For patients with subcortical, supratentorial ICH requiring surgical evacuation, MIS was associated with higherhigher rates of excellent outcomes compared to CC and lower rates of in-hospital mortality compared to DC. However, since key variables such as hematoma size and symptom severity were not available, residual confounding could not be excluded, and results should be interpreted cautiously. Dedicated prospective or randomized studies are needed to confirm these findings. Full article

(This article belongs to the Special Issue New Advances in Neurosurgery: Clinical Diagnosis, Treatment and Prognosis)

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14 pages, 985 KiB

Open AccessArticle

Exercise Hemodynamics and Sex-Specific Data in Asymptomatic Adults: An Exploratory Pilot Study

by Mi-Hyang Jung, So-Young Lee, Woo-Baek Chung, Jong-Chan Youn and Hae Ok Jung

Diagnostics 2025, 15(11), 1307; https://doi.org/10.3390/diagnostics15111307 - 23 May 2025

Abstract

Background: Understanding normal exercise hemodynamics is essential for assessing individuals with exertional dyspnea. This study utilized exercise echocardiography to gain insights into exercise hemodynamics in asymptomatic middle-aged to older adults without overt cardiovascular disease. Methods: We prospectively enrolled 30 individuals aged [...] Read more.

Background: Understanding normal exercise hemodynamics is essential for assessing individuals with exertional dyspnea. This study utilized exercise echocardiography to gain insights into exercise hemodynamics in asymptomatic middle-aged to older adults without overt cardiovascular disease. Methods: We prospectively enrolled 30 individuals aged 45–75 years without dyspnea, excluding those with left ventricular ejection fraction (LVEF) < 50% or significant heart/lung diseases. All participants underwent symptom-limited bicycle exercise echocardiography. Results: Two individuals exhibited early-stage dyspnea, leading to the inclusion of 28 individuals (mean age 61 ± 8 years, 50% female) in the final analysis. Throughout the exercise, the average E/e’ ratio increased from 8.3 ± 1.6 at rest to 9.7 ± 1.8 at 75 W (p = 0.001), while systolic pulmonary artery pressure (SPAP) rose from 23.0 ± 3.9 mmHg at rest to 41.2 ± 9.3 mmHg at 75 W (p < 0.001). Sex-specific analysis revealed a more pronounced elevation in SPAP during exercise among females (SPAP at 75 W, 45.5 ± 8.3 in females; 36.8 ± 8.3 mmHg in males, p = 0.011; p < 0.001 for interaction between sexes). Conclusions: In asymptomatic middle-aged to older adults, while there was a slight increase in left ventricular filling pressure and SPAP during exercise, the mean average E/e’ and SPAP at peak exercise were below 10 and 50 mmHg, respectively. Our findings also demonstrate sex-specific differences, with females exhibiting a more pronounced elevation in SPAP during exercise. Full article

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

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11 pages, 583 KiB

Open AccessArticle

Adenoviral Pharyngitis in the Paediatric Emergency Department: The Pivotal Role of Rapid Antigenic Testing

by Marco Denina, Francesco Del Monte, Emanuele Castagno, Giulia Tosoni, Samuele La Mendola, Federico Vigna, Alessandro Bondi, Angelo Giovanni Delmonaco and Claudia Bondone

Diagnostics 2025, 15(11), 1306; https://doi.org/10.3390/diagnostics15111306 - 22 May 2025

Abstract

Background: adenoviruses (AdVs) are DNA viruses that typically cause mild infections in immunocompetent children, and typically involve the respiratory and gastrointestinal tract. Adenoviral pharyngitis is a common paediatric illness, particularly in children under 4 years old. The aim of our 7-year retrospective study, [...] Read more.

Background: adenoviruses (AdVs) are DNA viruses that typically cause mild infections in immunocompetent children, and typically involve the respiratory and gastrointestinal tract. Adenoviral pharyngitis is a common paediatric illness, particularly in children under 4 years old. The aim of our 7-year retrospective study, conducted at a tertiary care paediatric emergency department (ED), was to describe the clinical and laboratory characteristics and management of patients with pharyngeal AdV infections. Specifically, we examined how the management of patients with adenoviral pharyngitis has evolved following the introduction of a rapid antigen nasopharyngeal swab test for AdVs, which has been performed directly in the ED since 2023. Methods: in this single-centre retrospective observational study, the demographic and clinical information for children discharged from the ED who had been diagnosed with a pharyngeal AdV infection between 1 January 2017 and 31 December 2023 were retrospectively reviewed. Moreover, we compared data before and after the introduction of rapid AdV antigenic swabs, which have been directly performed in the ED since the beginning of 2023. Statistical analysis was undertaken using the Student’s t-test and Pearson and Fisher’s exact test, as appropriate. Significance was set at p-value < 0.05. Results: during the study period, 172 children were diagnosed with adenoviral pharyngitis based on a positive swab. All patients were febrile, with a median duration of fever of 4 days. Blood tests were requested for 84.9% of patients at admission, resulting in a mean WBC count of 13,250/mmc and a mean CRP of 70.6 mg/L. The highest CRP median values were found on the third day of fever. Out of 383 swabs performed during 2017–2022, 13.6% were positive vs a 32% positive rate for the 372 swabs performed in 2023. The mean duration of observation in the ED before 2023 was 31.4 h vs. 10.4 h in 2023. Similarly, 9% of patients with adenoviral pharyngitis were admitted to a paediatric ward before 2023 and only 0.8% in 2023. Conclusions: the primary reason for ED admission in cases of adenoviral pharyngitis is fever lasting several days due to hyperinflammation. Differential diagnosis with bacterial infection is essential to limit the number of hospitalisations and inappropriate antibiotic therapy. The introduction of the rapid antigen nasopharyngeal swab has simplified the diagnosis of adenoviral pharyngitis, enabling timely and accurate differentiation from bacterial causes. Full article

(This article belongs to the Special Issue Laboratory Diagnosis of Infectious Disease: Advances and Challenges)

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18 pages, 1228 KiB

Open AccessArticle

The Biochemical–Imaging Connection: Urinary Noradrenaline and Fluorodeoxyglucose-Positron Emission Tomography in Unresectable or Metastatic Pheochromocytomas and Paragangliomas

by Junki Takenaka, Shiro Watanabe, Takashige Abe, Satoshi Takeuchi, Kenji Hirata, Rina Kimura, Hiroshi Ishii, Naoto Wakabayashi, Mungunkhuyag Majigsuren and Kohsuke Kudo

Diagnostics 2025, 15(11), 1305; https://doi.org/10.3390/diagnostics15111305 - 22 May 2025

Abstract

Background/Objectives: Pheochromocytomas and paragangliomas (PPGLs) are rare tumors of neural crest origin that secrete varying levels of catecholamines. [¹⁸F]Fluorodeoxyglucose-positron emission tomography (FDG-PET) is a valuable tool for the detection of metastases and the prediction of prognoses. However, varying FDG avidities in [...] Read more.

Background/Objectives: Pheochromocytomas and paragangliomas (PPGLs) are rare tumors of neural crest origin that secrete varying levels of catecholamines. [¹⁸F]Fluorodeoxyglucose-positron emission tomography (FDG-PET) is a valuable tool for the detection of metastases and the prediction of prognoses. However, varying FDG avidities in PPGLs raise concerns regarding cost-effectiveness and unnecessary radiation exposure. Catecholamine secretion patterns are associated with metastasis and clinical outcomes. This study aimed to explore the relationships among FDG avidity, catecholamine levels, and clinical factors in patients with PPGLs. Methods: This retrospective study included 25 patients with unresectable or metastatic PPGLs scheduled for [¹³¹I]metaiodobenzylguanidine therapy with FDG-PET data available within 40 days of urine catecholamine measurements. FDG avidity was assessed using semiquantitative parameters such as the maximum standardized uptake value (SUVmax), total metabolic tumor volume (MTV), and total lesion glycolysis (TLG). Urine catecholamine levels were quantified. Logistic regression and Spearman’s correlation were performed to evaluate the relationship between FDG parameters and urinary catecholamine levels. Results: Urinary noradrenaline levels were significantly higher in patients with FDG-avid lesions than in those without (726.25 μg/day vs. 166.3 μg/day, p = 0.001). Noradrenaline levels showed significant positive correlations with SUVmax, MTV, and TLG (ρ = 0.527, 0.541, and 0.557, respectively; all p < 0.01). Urinary noradrenaline levels predicted FDG avidity with an AUC of 0.849; a cutoff value of 647.5 μg/day achieved 55.6% sensitivity and 100% specificity. Conclusions: Urinary noradrenaline levels were significantly associated with FDG avidity in PPGLs, suggesting their potential utility in predicting FDG-PET outcomes. Therefore, FDG-PET may be unnecessary in PPGL patients with low urinary noradrenaline levels. These findings may help optimize imaging strategies for patients with PPGLs. Full article

(This article belongs to the Special Issue Nuclear Medicine and Molecular Imaging in Cancer Diagnosis, Therapy, and Treatment Assessment)

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