Diagnostics

2 pages, 155 KB

Open AccessComment

Clarifying the Clinical Utility of NTAR/RGR for PAH and CTEPH. Comment on Iancu et al. Evaluating NT-proBNP-to-Albumin (NTAR) and RDW-to-eGFR (RGR) Ratios as Biomarkers for Predicting Hospitalization Duration and Mortality in Pulmonary Arterial Hypertension (PAH) and Chronic Thromboembolic Pulmonary Hypertension (CTEPH). Diagnostics 2025, 15, 2126

by Gianluca Pagnoni, Aurora Vicenzi and Francesca Coppi

Diagnostics 2026, 16(1), 55; https://doi.org/10.3390/diagnostics16010055 (registering DOI) - 23 Dec 2025

Abstract

We read with interest the work by Iancu et al [...] Full article

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

11 pages, 486 KB

Open AccessArticle

Diagnostic Value of CA-125 and Other Tumor Biomarkers in Children with Suspected Malignancy: A Retrospective Cohort Study

by Şule Çalışkan Kamış, Metin Çil and Begül Yağcı

Diagnostics 2026, 16(1), 54; https://doi.org/10.3390/diagnostics16010054 (registering DOI) - 23 Dec 2025

Abstract

Background/Objective: Tumor biomarkers are widely used in adult oncology, but their diagnostic value in pediatric patients remains unclear. This study aimed to evaluate the clinical significance of CA-125, CA 19-9, CA 15-3, and CEA in children evaluated for suspected malignancy. Methods: [...] Read more.

Background/Objective: Tumor biomarkers are widely used in adult oncology, but their diagnostic value in pediatric patients remains unclear. This study aimed to evaluate the clinical significance of CA-125, CA 19-9, CA 15-3, and CEA in children evaluated for suspected malignancy. Methods: This retrospective study included 211 pediatric patients (0–18 years) referred to a tertiary pediatric oncology center. Serum levels of the four biomarkers were analyzed in relation to patient demographics, imaging findings, and final diagnoses. Statistical analyses included chi-square, Mann–Whitney U, Kolmogorov–Smirnov tests, and receiver operating characteristic (ROC) curve analysis. Results: Of the 211 patients, 35 (16.6%) were diagnosed with malignancy. Elevated CA-125 was significantly associated with malignancy (p = 0.002), particularly among postpubertal female patients. Imaging abnormalities were more frequent in CA-125–positive cases (p < 0.001) and in patients with confirmed malignancy. ROC curve analysis demonstrated that CA-125 had an area under the curve (AUC) of 0.642, indicating modest discriminatory power. No significant associations were found for CA 19-9, CA 15-3, or CEA. Conclusions: CA-125 may serve as an adjunctive diagnostic biomarker in pediatric oncology, particularly in postpubertal girls and when interpreted alongside imaging findings. Other markers showed limited diagnostic value. Given its low sensitivity, CA-125 is not suitable as a standalone screening test in children. Larger, multicenter prospective studies are needed to establish pediatric-specific reference ranges and validate these findings. Full article

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

26 pages, 1023 KB

Open AccessArticle

Non-Glycemic Clinical Data for Type 2 Diabetes Detection in Mexican Adults: A Comparative Analysis of Atherogenic Indices, Statistical Transformations, and Machine Learning Algorithms

by Martin Hazael Guerrero-Flores, Valeria Maeda-Gutiérrez, Carlos E. Galván-Tejada, Jorge I. Galván-Tejada, Miguel Cruz, Luis Alberto Flores-Chaires, Karina Trejo-Vázquez, Rafael Magallanes-Quintanar and Javier Saldívar

Diagnostics 2026, 16(1), 53; https://doi.org/10.3390/diagnostics16010053 - 23 Dec 2025

Abstract

Background: Type 2 diabetes (T2D) is a growing public health problem in Mexico. Lipid profile alterations have been shown to appear years before changes in glycemic biomarkers, and some of the latter are limited in availability, especially in underserved settings. Therefore, anthropometric variables [...] Read more.

Background: Type 2 diabetes (T2D) is a growing public health problem in Mexico. Lipid profile alterations have been shown to appear years before changes in glycemic biomarkers, and some of the latter are limited in availability, especially in underserved settings. Therefore, anthropometric variables and lipids represent relevant early indicators for the early detection of the disease. This study evaluates the capacity of non-glycemic clinical data—including lipid profile and anthropometric indicators—to detect T2D using machine learning, and compares the performance of different feature engineering approaches. Methods: Using more than a thousand clinical records of Mexican adults, three experiments were developed: (1) a distribution and normality analysis to characterize the variability of lipid variables; (2) an evaluation of the predictive power of multiple atherogenic indices (Castelli I, Castelli II, TG/HDL, and AIP); and (3) the implementation of statistical transformations (logarithmic, quare-root, and Z-standardization) to stabilize variance and improve feature quality. Logistic regression, SVM-RBF, random forest, and XGBoost models were trained on each feature set and evaluated using accuracy, sensitivity, specificity, F1-score, and area under the ROC curve. Results: The AIP index showed the greatest discriminatory power among the atherogenic indices, while normality-based transformations improved the performance of distribution-sensitive models, such as SVM. In the final experiment, the SVM-RBF and XGBoost models achieved AUC values greater than 0.90, demonstrating the feasibility of a diagnostic approach based exclusively on non-glycemic data. Conclusions: The findings indicate that the transformed lipid profile and anthropometric variables can constitute a solid and accessible alternative for the early detection of T2D in clinical and public health contexts, offering a robust methodological framework for future predictive applications in the absence of traditional glycemic biomarkers. Full article

(This article belongs to the Special Issue AI and Digital Health for Disease Diagnosis and Monitoring, 2nd Edition)

13 pages, 656 KB

Open AccessArticle

Comparative Analysis of Coagulation and Liver Parameters in Individuals with Alcohol and Substance Use Disorders and Healthy Controls

by Şeyma Bardakçı, Muhammed Raşit Bardakçı, Derya Güzel Erdoğan, Abdülkadir Aydın and Ahmet Bulent Yazici

Diagnostics 2026, 16(1), 52; https://doi.org/10.3390/diagnostics16010052 - 23 Dec 2025

Abstract

Background/Objectives: Alcohol Use Disorder (AUD) and Substance Use Disorders (SUDs) can affect both the liver, where clotting factors are synthesized, and the coagulation system, which prevents acute bleeding. Methods: This study included 451 inpatients undergoing addiction detoxification and 150 healthy controls. Patients were [...] Read more.

Background/Objectives: Alcohol Use Disorder (AUD) and Substance Use Disorders (SUDs) can affect both the liver, where clotting factors are synthesized, and the coagulation system, which prevents acute bleeding. Methods: This study included 451 inpatients undergoing addiction detoxification and 150 healthy controls. Patients were stratified by substance type: Alcohol (n = 110), Cannabinoid (n = 71), Methamphetamine (n = 110), Multiple-Substance (Methamphetamine + Cannabinoid, n = 110), and Opioid (n = 50) users. Age-matched control groups (mean ages 45, n = 50; 30, n = 100) were used. Serum levels of Ca, INR, PT, APTT, PLT, AST, and ALT, alongside sociodemographic variables, were assessed. Results: Significant group differences were observed in ALT, AST, PT, APTT, and PLT (p < 0.001). Notably, PT was lower in Multiple Substance and Methamphetamine users; APTT was elevated in Cannabinoid users; AST was higher in Alcohol users; and Methamphetamine and Opioid users exhibited both decreased AST and ALT. Post hoc analyses confirmed substance-specific effects (p < 0.001). Regular cigarette use was significantly more prevalent among alcohol and substance user groups compared to controls; however, smoking did not exert a significant effect on the evaluated biochemical or coagulation parameters. Conclusions: These findings demonstrate that liver enzymes and coagulation parameters can vary significantly by substance type. Observed alterations in AST, ALT, PT, APTT, and PLT suggest that substance use may exert substance-specific effects on hepatic and haemostatic function, highlighting potential risks for bleeding or thrombotic complications. Monitoring these parameters in AUD and SUD patients could provide valuable clinical insights, allowing for more tailored and proactive management strategies. While the underlying mechanisms remain to be fully elucidated, these results emphasize the importance of considering substance-specific physiological impacts when assessing liver and coagulation health in addicted populations. Full article

(This article belongs to the Section Clinical Laboratory Medicine)

22 pages, 762 KB

Open AccessReview

MicroRNAs as Diagnostic and Prognostic Biomarkers in Melanoma and Non-Melanoma Skin Cancers: An Updated Review

by Alexandra Oiegar, Adrian Bogdan Tigu, Adrian Baican, Elisabeta Candrea, Mircea Negrutiu and Sorina Danescu

Diagnostics 2026, 16(1), 51; https://doi.org/10.3390/diagnostics16010051 - 23 Dec 2025

Abstract

MicroRNAs (miRNAs) have emerged as critical post-transcriptional regulators in melanoma and non-melanoma skin cancers (NMSCs), yet their full biological and clinical significance remains incompletely defined. This review synthesizes current evidence on miRNA dysregulation across basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC), [...] Read more.

MicroRNAs (miRNAs) have emerged as critical post-transcriptional regulators in melanoma and non-melanoma skin cancers (NMSCs), yet their full biological and clinical significance remains incompletely defined. This review synthesizes current evidence on miRNA dysregulation across basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC), Merkel cell carcinoma (MCC), and melanoma, emphasizing their diagnostic, prognostic, and therapeutic relevance. In BCC, distinct miRNA expression signatures differentiate tumor tissue from normal skin and correlate with histopathological subtypes. miR-383-5p, miR-4705, miR-145-5p, and miR-18a show strong diagnostic potential, while downregulation of miR-34a is consistently associated with greater tumor aggressiveness. Subtype-specific profiles further delineate superficial versus infiltrative lesions, highlighting miRNAs as markers of tumor behavior. cSCC similarly demonstrates characteristic miRNA alterations. miR-31 is markedly upregulated during the transition from actinic keratosis to invasive carcinoma, whereas high miR-205 and low miR-203 levels correlate with poor and favorable prognosis, respectively. Regarding MCC, many miRNAs such as miR-375 and miR-182 may present a clinical value for potential biomarkers, as they are upregulated in MCC. Merkel cell carcinoma has also been linked with Merkel cell polyomavirus (MCPyV). Melanoma exhibits a complex miRNA landscape, including oncogenic miR-18a-5p and miR-146a, and tumor-suppressive miR-128-3p. Several miRNAs correlate with metastatic potential, BRAF mutation status, and therapeutic resistance, particularly miR-181a/b, underscoring their potential as predictive biomarkers. Overall, current evidence supports miRNAs as promising diagnostic, prognostic, and predictive biomarkers in cutaneous oncology. Standardized methodologies and large-scale validation remain essential for their integration into routine clinical practice. Full article

(This article belongs to the Special Issue Advances in Diagnosis of Skin and Superficial Tissues Disorders—“Old and Emerging” Diagnostic Tools—2nd Edition)

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13 pages, 1052 KB

Open AccessArticle

Immunoglobulin Free Light Chains as a Biomarker of Inflammation and Heart Failure in Myocarditis and Non-Inflammatory Heart Disease

by Olga Blagova, Yulia Lutokhina, Maria Kozhevnikova, Elena Zheleznykh and Evgeniya Kogan

Diagnostics 2026, 16(1), 50; https://doi.org/10.3390/diagnostics16010050 - 23 Dec 2025

Abstract

Aim: to study the level of immunoglobulin FLC in patients with myocarditis in comparison with non-inflammatory heart diseases, and FLC’s correlation with the severity of CHF. Methods: Ninety-nine patients (41 women, 59.6 ± 14.6 y.o.) were included in the study: 50 [...] Read more.

Aim: to study the level of immunoglobulin FLC in patients with myocarditis in comparison with non-inflammatory heart diseases, and FLC’s correlation with the severity of CHF. Methods: Ninety-nine patients (41 women, 59.6 ± 14.6 y.o.) were included in the study: 50 patients with myocarditis [confirmed by myocardial biopsy (n = 20) and/or cardiac MRI]; 49 patients with non-inflammatory heart disease. CHF was diagnosed in 66% and 65% of patients, respectively. The levels of FLC were determined using the ‘Cloneus S-FLC-K TIA Kit’ and ‘Cloneus S-FLC-L TIA Kit’ reagents. Results: Elevated FLC levels were found in 56% of patients with myocarditis and in 67% of comparison group patients (p > 0.05). Mean FLC kappa levels were 13.4 [11.7; 16.7] and 16.0 [11.3; 23.7] mg/L, FLC lambda 22.7 [16.7; 32.4] and 24.7 [18.1; 39.1] mg/L, FLC kappa/lambda ratio 0.62 [0.50; 0.73] and 0.65 [0.56; 0.76] in myocarditis and comparison groups, respectively; there were no significant differences between groups. Both groups showed correlations of FLC levels with levels of CRP and leukocytes, as well as with glomerular filtration rate, CHF NYHA class, and left ventricular ejection fraction. Only in patients with myocarditis did we observe a significant correlation between both kappa and lambda FLC and NT-proBNP (r = 0.528, p = 0.004, and r = 0.756, p < 0.001) and high-sensitivity troponin (r = 0.829, p = 0.042) levels. Conclusions: Increased FLC level may be considered an important pathogenetic link reflecting both specific mechanisms of myocarditis and severity of CHF. The determination of FLC can be used as an additional diagnostic marker, as well as one predictor of the decompensated course of myocarditis. Full article

(This article belongs to the Special Issue Advanced Diagnostic Approaches in Cardiovascular Diseases: From Imaging to Biomarkers)

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26 pages, 976 KB

Open AccessReview

From Radical Resection to Precision Surgery: Integrating Diagnostic Biomarkers, Radiomics-Based Predictive Models, and Perioperative Systemic Therapy in Head and Neck Oncology

by Luiz P. Kowalski, Carol R. Bradford, Jonathan J. Beitler, Juan Pablo Rodrigo, Orlando Guntinas-Lichius, Petra Ambrosch, Arlene A. Forastiere, Karthik N. Rao, Marc Hamoir, Nabil F. Saba, Alvaro Sanabria, Primoz Strojan, Kevin Thomas Robbins and Alfio Ferlito

Diagnostics 2026, 16(1), 49; https://doi.org/10.3390/diagnostics16010049 - 23 Dec 2025

Abstract

Head and neck cancer surgery has evolved from radical organ-sacrificing procedures to function-preserving approaches integrated within multidisciplinary frameworks. This comprehensive literature review, concentrating on studies from the past five years while incorporating relevant publications from the last three decades and landmark historical papers, [...] Read more.

Head and neck cancer surgery has evolved from radical organ-sacrificing procedures to function-preserving approaches integrated within multidisciplinary frameworks. This comprehensive literature review, concentrating on studies from the past five years while incorporating relevant publications from the last three decades and landmark historical papers, examines the evolving role of surgery emphasizing diagnostic methodologies including comprehensive genomic profiling, validated imaging biomarkers, and their clinical integration for treatment selection and response prediction. Modern surgical practice demonstrates a paradigm shift toward precision medicine through validated diagnostic technologies. Comprehensive genomic profiling identifies clinically actionable alterations in over 90% of head and neck squamous cell carcinomas, with tumor mutational burden serving as a validated predictive biomarker for immunotherapy response. Programmed death-ligand 1 (PD-L1) combined positive score functions as a validated diagnostic biomarker for immunotherapy efficacy, demonstrating significant clinical benefit in biomarker-selected populations. Radiomics-based predictive models utilizing machine learning algorithms achieve diagnostic accuracies exceeding 85% for treatment response prediction when validated across independent cohorts. Quantitative ultrasound spectroscopy combined with magnetic resonance imaging radiomics demonstrates high sensitivity and specificity for radiation response prediction. Habitat imaging techniques characterizing tumor microenvironmental heterogeneity predict pathologic complete response to neoadjuvant chemoimmunotherapy with area under the curve values approaching 0.90 in validation studies. Integration of these diagnostic methodologies enables response-adaptive treatment strategies, with neoadjuvant chemotherapy facilitating mandibular preservation and adjuvant therapy omission in over half of human papillomavirus (HPV)-associated cases following surgical downstaging. Clinical validation of these diagnostic platforms enables accurate treatment response prediction and informed surgical decision-making, though standardization across institutions and demonstration of survival benefits through prospective trials remain essential for broader implementation. Full article

(This article belongs to the Special Issue Clinical Diagnosis of Otorhinolaryngology)

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18 pages, 2738 KB

Open AccessCase Report

Ultrasound Images That Speak: Assessing the Therapeutic Decision in the Emergency Department Regarding the Risk–Benefit Ratio of Systemic Thrombolysis in Intermediate-High-Risk Pulmonary Embolism—A Case Report

by Adela Golea, Raluca Mihaela Tat, Carina Adam, Sonia Luka, Mirela Anca Stoia and Ștefan Cristian Vesa

Diagnostics 2026, 16(1), 48; https://doi.org/10.3390/diagnostics16010048 - 23 Dec 2025

Abstract

Background: The management of acute pulmonary embolism (PE) in the Emergency Department (ED) remains challenging, particularly in hemodynamically and respiratory stable patients with minimal symptoms. Diagnostic and therapeutic difficulties are further compounded when the condition is complicated by a mobile right atrial [...] Read more.

Background: The management of acute pulmonary embolism (PE) in the Emergency Department (ED) remains challenging, particularly in hemodynamically and respiratory stable patients with minimal symptoms. Diagnostic and therapeutic difficulties are further compounded when the condition is complicated by a mobile right atrial (RA) thrombus, representing an extreme-risk phenotype. Case Presentation: We report the case of a 65-year-old male with a single known venous thromboembolism risk factor-chronic venous insufficiency-who presented to the ED following a transient episode of severe dyspnea at home. On admission, he was hemodynamically and respiratory stable, without the need for oxygen supplementation. Arterial blood gas analysis revealed a metabolically compensated acidosis with elevated lactate, while cardiac biomarkers were moderately increased. Emergency point-of-care transthoracic echocardiography (POCUS-TTE) demonstrated severe right ventricular (RV) dysfunction and a large, mobile intracardiac thrombus prolapsing through the tricuspid valve. Computed Tomography Pulmonary Angiography confirmed pulmonary embolism and revealed a massive and extensive bilateral thrombotic burden (Qanadli score 32 points). Given the extreme risk for fatal embolization, immediate full-dose systemic thrombolysis with Alteplase (100 mg over 2 h) was initiated in the ED. Thrombolysis was completed without hemorrhagic complications. Follow-up POCUS-TTE at 2 h showed complete resolution of the intracardiac thrombus and significant improvement of RV function (RV/RA gradient reduced from 40 mmHg to 28 mmHg). Conclusions: This case highlights the effectiveness and safety of early systemic thrombolysis guided by ED POCUS-TTE in PE with a massive thrombotic burden, complicated by a mobile intracardiac thrombus, even in the absence of shock. Such prompt intervention may reduce mortality risk in intermediate-to-high-risk PE subsets, despite limited guidance in current clinical recommendations. Full article

(This article belongs to the Special Issue New Trends in Ultrasound Imaging)

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15 pages, 3223 KB

Open AccessArticle

First Clinical Description of Coagulation of Whole Blood with Resonant Acoustic Rheometry

by Connor M. Bunch, Weiping Li, Kiera Downey, Timothy L. Hall, Allen Chehimi, Samuel J. Thomas, Afsheen Mansoori, Miguel Velasco, Marie N. Karam, Jenny Chen, Jacob Tuttle, Matthew R. Walsh, Scott G. Thomas, Mark M. Walsh, Joseph B. Miller, Jan P. Stegemann and Cheri X. Deng

Diagnostics 2026, 16(1), 47; https://doi.org/10.3390/diagnostics16010047 - 23 Dec 2025

Abstract

Background/Objectives: The timely evaluation of blood clot formation and breakdown is essential in the care of patients with severe bleeding or critical illness. Resonant acoustic rheometry is a novel, non-contact ultrasound method that measures changes in the viscoelastic properties of blood in [...] Read more.

Background/Objectives: The timely evaluation of blood clot formation and breakdown is essential in the care of patients with severe bleeding or critical illness. Resonant acoustic rheometry is a novel, non-contact ultrasound method that measures changes in the viscoelastic properties of blood in a standard microplate format. Here, we present the first clinical description of whole blood coagulation and fibrinolysis assessed with resonant acoustic rheometry, with paired thromboelastography measurements for comparison. Methods: In this retrospective analysis, whole blood samples from three critically ill patients were divided and tested under four different conditions that included a control mixture, kaolin activation, tissue factor activation, and a tissue factor mixture supplemented with tissue plasminogen activator. The resonant acoustic rheometry system obtained real time measurements of resonant surface waves and displacements from the samples. Heat maps and spectrograms of the resonant surface waves were analyzed to determine the onset of clotting, the rate of viscoelastic stiffening, the time to maximum rigidity, and the onset as well as magnitude of fibrinolysis. These measurements were compared with thromboelastography reaction time, clot strength, fibrinogen contribution, and lysis values. Results: Resonant acoustic rheometry detected reproducible transitions from liquid to clot and from clot to lysis in all samples. Activator-dependent changes in clot initiation and propagation matched the expected hierarchy observed in thromboelastography. Significantly, samples exposed to tissue plasminogen activator demonstrated a clear fall in resonant frequency and a corresponding rise in surface displacement that reflected fibrinolysis. The technique also reproduced clinically meaningful patterns of hemostasis that aligned with each patient’s underlying disease. Conclusions: Whole blood clotting can be measured with resonant acoustic rheometry in a manner that aligns with established clinical assays. These results suggest strong potential for future use of resonant acoustic rheometry as a cost-effective, complementary platform for rapid, scalable, and clinically informative hemostatic assessment. Full article

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

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16 pages, 3554 KB

Open AccessArticle

Early Detection of Cystoid Macular Edema in Retinitis Pigmentosa Using Longitudinal Deep Learning Analysis of OCT Scans

by Farhang Hosseini, Farkhondeh Asadi, Reza Rabiei, Arash Roshanpoor, Hamideh Sabbaghi, Mehrnoosh Eslami and Rayan Ebnali Harari

Diagnostics 2026, 16(1), 46; https://doi.org/10.3390/diagnostics16010046 - 23 Dec 2025

Abstract

Background/Objectives: Retinitis pigmentosa (RP) is a progressive hereditary retinal disorder that frequently leads to vision loss, with cystoid macular edema (CME) occurring in approximately 10–50% of affected patients. Early detection of CME is crucial for timely intervention, yet most existing studies lack [...] Read more.

Background/Objectives: Retinitis pigmentosa (RP) is a progressive hereditary retinal disorder that frequently leads to vision loss, with cystoid macular edema (CME) occurring in approximately 10–50% of affected patients. Early detection of CME is crucial for timely intervention, yet most existing studies lack longitudinal data capable of capturing subtle disease progression. Methods: We propose a deep learning–based framework utilizing longitudinal optical coherence tomography (OCT) imaging for early detection of CME in patients with RP. A total of 2280 longitudinal OCT images were preprocessed using denoising and data augmentation techniques. Multiple pre-trained deep learning architectures were evaluated using a patient-wise data split to ensure robust performance assessment. Results: Among the evaluated models, ResNet-34 achieved the best performance, with an accuracy of 98.68%, specificity of 99.45%, and an F1-score of 98.36%. Conclusions: These results demonstrate the potential of longitudinal OCT–based artificial intelligence as a reliable, non-invasive screening tool for early CME detection in RP. To the best of our knowledge, this study is the first to leverage longitudinal OCT data for AI-driven CME prediction in this patient population. Full article

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

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13 pages, 4226 KB

Open AccessArticle

Multi-Center Validation of Artificial Intelligence-Based Video Analysis Platform for Automatic Evaluation of Swallowing Disorders

by Chang-Won Jeong, Dong-Wook Lim, Si-Hyeong Noh, Hee-Kyung Moon, Chul Park, Nayeon Ko and Min-Su Kim

Diagnostics 2026, 16(1), 45; https://doi.org/10.3390/diagnostics16010045 - 23 Dec 2025

Abstract

Background: Videofluoroscopic swallow study (VFSS) is a key examination for assessing swallowing function. Although several artificial intelligence (AI) models for VFSS interpretation have shown high predictive accuracy through internal validations, AI models that have undergone external validation are rare. This study aims to [...] Read more.

Background: Videofluoroscopic swallow study (VFSS) is a key examination for assessing swallowing function. Although several artificial intelligence (AI) models for VFSS interpretation have shown high predictive accuracy through internal validations, AI models that have undergone external validation are rare. This study aims to develop an AI model that automatically diagnoses aspiration and penetration from VFSS videos and to evaluate the model’s performance through multicenter external validation. Methods: Among the 2343 VFSS videos collected, 309 cases of Q1-grade videos, which were free of artifacts and clearly showed the airway and vocal cords, were included in the internal validation dataset. The training, internal validation, and test datasets were divided in a 7:1:2 ratio, with 2012 images (aspiration = 532, penetration = 932, no airway invasion = 548) used for training. The AI model was developed and trained using You Only Look Once version 9, model c (YOLOv9_c). External validation of the AI model was conducted using 138 Q1 and Q2-grade VFSS videos from two different hospitals. Results: According to the internal validation, the YOLOv9_c model showed a training accuracy of 98.1%, a validation accuracy of 97.8%, and a test accuracy of 61.5%. From the confusion matrix analysis, the AI model’s diagnostic accuracy for aspiration in VFSS videos was 0.76 (AUC = 0.70), and for penetration, the diagnostic accuracy was 0.66 (AUC = 0.65). According to the external validation, the AI model demonstrated good performance in diagnosing aspiration (precision: 90.2%, AUC = 0.79) and penetration (precision: 78.3%, AUC = 0.80). The overall diagnostic accuracy of external validation for VFSS videos was 80.4%. Conclusions: We developed an AI model that automatically diagnoses aspiration and penetration when an entire VFSS video is input, and external validation showed good accuracy. In the future, to improve the performance of this AI model and facilitate its clinical application, research using training and validation with VFSS video data from more hospitals is needed. Full article

(This article belongs to the Special Issue Artificial Intelligence for Clinical Diagnostic Decision Making)

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15 pages, 517 KB

Open AccessArticle

The Thrombopoietic Signature of Preeclampsia: Diagnostic and Monitoring Insights from the Immature Platelet Fraction

by Ilkay Er, Senol Sentürk, Medeni Arpa and Nalan Kuruca

Diagnostics 2026, 16(1), 44; https://doi.org/10.3390/diagnostics16010044 - 23 Dec 2025

Abstract

Background: Preeclampsia is a major obstetric disorder characterized by platelet activation and dysregulated thrombopoiesis. While conventional platelet indices reflect platelet morphology, the immature platelet fraction (IPF) provides insight into thrombopoietic activity. This study assessed IPF discrimination at presentation and its early post-treatment change [...] Read more.

Background: Preeclampsia is a major obstetric disorder characterized by platelet activation and dysregulated thrombopoiesis. While conventional platelet indices reflect platelet morphology, the immature platelet fraction (IPF) provides insight into thrombopoietic activity. This study assessed IPF discrimination at presentation and its early post-treatment change in preeclampsia while controlling for potential confounding factors. Methods: In a prospective design, demographic and laboratory parameters—particularly platelet indices—were evaluated in women with preeclampsia and normotensive pregnant controls. Measurements were obtained at diagnosis and repeated 24–48 h after treatment, including initiation of medical treatment or delivery. Logistic regression and ROC analyses were performed, adjusting for age and gestational age. Results: Sixty-four women with preeclampsia and 25 normotensive controls were included; the preeclampsia group was older (31.3 ± 5 vs. 28.4 ± 4 years), and delivery occurred in 73.4%. At diagnosis, IPF, MPV, and PDW were higher, and platelet counts were lower compared with controls. After treatment, IPF decreased markedly (ΔIPF = 3.4; p < 0.001), accompanied by reductions in MPV and PDW, while platelet counts remained unchanged in the preeclampsia group. ΔIPF showed subtype-related differences, being higher in late-onset preeclampsia. Only IPF retained an independent association with preeclampsia (OR = 27.29; p = 0.006), whereas age, platelet count, MPV, PDW, BUN, and CRP were not significant. On ROC analysis, IPF demonstrated strong diagnostic performance (AUC = 0.992; cut-off ≥4%), with 98.4% sensitivity and 100% specificity. Conclusions: Easily measurable as part of a routine complete blood count, IPF may support diagnostic evaluation and clinical monitoring, consistent with its early post-treatment decline and subtype-related patterns. Full article

(This article belongs to the Special Issue Advances in Maternal and Fetal Medicine Research: from Diagnostics to Prognosis)

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16 pages, 281 KB

Open AccessReview

Understanding Current Trends and Advances in Transarterial Radioembolization Dosimetry

by Shamar Young, Kiyon Naser-Tavakolian, Abin Sajan, Stephen Reis, Gregory Woodhead, Tyler Sandow, Juan Gimenez, Kirema Garcia-Reyes, Zachary Berman and Venkatesh P. Krishnasamy

Diagnostics 2026, 16(1), 43; https://doi.org/10.3390/diagnostics16010043 - 23 Dec 2025

Abstract

Transarterial radioembolization (TARE) is an established therapy for primary and secondary hepatic malignancies. Outcomes depend heavily on dosimetry, which has evolved from empirical and body-surface-area methods to partition and voxel-based approaches. This review summarizes current evidence for advanced (personalized) dosimetry across tumor types, [...] Read more.

Transarterial radioembolization (TARE) is an established therapy for primary and secondary hepatic malignancies. Outcomes depend heavily on dosimetry, which has evolved from empirical and body-surface-area methods to partition and voxel-based approaches. This review summarizes current evidence for advanced (personalized) dosimetry across tumor types, highlights emerging dose–response concepts, and outlines practical barriers and implementation strategies. A narrative review of peer-reviewed clinical studies and trials evaluating dosimetry in TARE, with emphasis on hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (iCCA), metastatic colorectal cancer (mCRC), neuroendocrine tumor (NET), and breast cancer liver metastases, was performed with comparison of single-compartment medical internal radiation dosimetry method (MIRD), partition (multicompartment) methods, and voxel-based dosimetry methodologies. Personalized dosimetry improves outcomes in multiple tumor types. A randomized trial in HCC showed superior overall survival with partition-based dosing versus MIRD. In selective HCC treatments, voxel-derived metrics (e.g., D95) correlate with complete pathologic necrosis, suggesting benefit beyond mean dose targets. For iCCA, data associate higher tumor doses with better radiologic response, progression-free survival, and downstaging. In mCRC, voxel-based and threshold analyses link specific tumor and margin doses with metabolic/radiographic response and survival. Smaller series in NET and breast cancer indicate dose–response relationships using advanced dosimetry. Evidence supports broader adoption of advanced dosimetry in TARE. Emerging strategies that ensure adequate coverage of the “coldest” tumor regions and thoughtful particle-load planning may further optimize results. Standardized protocols, prospective validation, and scalable workflows are needed to accelerate implementation. Full article

(This article belongs to the Special Issue Interventional Radiology in 2025–2026: From Technological Innovation to Clinical Optimization)

13 pages, 3572 KB

Open AccessArticle

Diagnostic Performance of Ring Aperture Retro Mode Imaging for Detecting Pigment Migration in Age-Related Macular Degeneration

by Thomas Desmettre, Gerardo Ledesma-Gil and Michel Paques

Diagnostics 2026, 16(1), 42; https://doi.org/10.3390/diagnostics16010042 - 23 Dec 2025

Abstract

Background/Objectives: Pigment migration is a key biomarker of progression in age-related macular degeneration (AMD). This study assessed the diagnostic performance of ring aperture Retro mode (RAR) imaging for detecting pigment migration and compared its performance with established multimodal imaging techniques. Methods: [...] Read more.

Background/Objectives: Pigment migration is a key biomarker of progression in age-related macular degeneration (AMD). This study assessed the diagnostic performance of ring aperture Retro mode (RAR) imaging for detecting pigment migration and compared its performance with established multimodal imaging techniques. Methods: This retrospective study included 80 eyes from 61 consecutive patients with AMD who underwent multimodal imaging with color fundus images (CFIs), fundus autofluorescence (FAF), RAR imaging (Mirante, NIDEK), and en face optical coherence tomography (OCT) with B-scans (Cirrus HD-OCT 5000, Zeiss). Two independent retina specialists graded the AMD stage and the presence of pigment migration across modalities. Sensitivity and positive predictive value (PPV) of RAR were calculated using en face OCT as the reference standard. Results: RAR demonstrated high diagnostic performance, with a sensitivity of 94.7% and a PPV of 93.4% relative to en face OCT. RAR frequently identified pigment migration that was not visible on CFI or FAF, particularly in early AMD and in eyes with media opacity. Distinct morphologic patterns—including hyperreflective foci, thickened retinal pigment epithelium, refractile drusen, and cuticular drusen—were consistently identifiable on RAR. In four eyes with geographic atrophy, RAR detected perifoveal pigment redistribution at least six months before foveal involvement was confirmed by OCT and FAF. Conclusions: RAR imaging is a rapid, sensitive, and clinically practical technique for detecting pigment migration in AMD. By complementing en face OCT and enhancing visualization in cases where standard imaging is limited, RAR may strengthen early disease surveillance, support prognostic assessment, and improve multimodal diagnostic workflows in routine practice. Full article

(This article belongs to the Special Issue Diagnosis and Management of Ophthalmic Disorders)

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12 pages, 899 KB

Open AccessArticle

Evaluation of OCT Angiography Parameters as Biomarkers for Glaucoma Progression

by Konstantina Kancheva, Mladena Radeva, Igor B. Resnick and Zornitsa Zlatarova

Diagnostics 2026, 16(1), 35; https://doi.org/10.3390/diagnostics16010035 - 23 Dec 2025

Abstract

Background: Optical coherence tomography angiography (OCT-A) provides quantitative assessment of retinal and peripapillary microvasculature and has emerged as a promising tool for glaucoma diagnostics. However, its sensitivity for detecting early glaucomatous progression over short intervals remains uncertain. This study evaluated cross-sectional and short-term [...] Read more.

Background: Optical coherence tomography angiography (OCT-A) provides quantitative assessment of retinal and peripapillary microvasculature and has emerged as a promising tool for glaucoma diagnostics. However, its sensitivity for detecting early glaucomatous progression over short intervals remains uncertain. This study evaluated cross-sectional and short-term longitudinal OCT-A vessel density (VD) metrics in primary open-angle glaucoma (POAG) and explored their relationships with structural (RNFL) and functional (MD) measures. Methods: Sixty eyes (30 POAG, 30 controls) underwent baseline and 6-month examinations including intraocular pressure (IOP), standard automated perimetry (SAP), structural OCT, and OCT-A (RTVue XR Avanti; AngioVue). Parameters analyzed included peripapillary VD (PP-VD), parafoveal VD (PF-VD), foveal avascular zone (FAZ) metrics, FD-300, and RNFL thickness. Between-group comparisons used t-tests or Mann–Whitney U tests. Effect sizes (Cohen’s d), 95% confidence intervals (CI), and ANCOVA models (adjusted for baseline, age, and sex) were included. Longitudinal change was defined as Δ = 6 months − baseline. Pearson correlations evaluated structure–vascular associations. Results: At baseline, POAG eyes showed significantly lower PP-VD, PF-VD, thinner RNFL, and worse MD (all p < 0.001). Strong correlations were observed between RNFL and PP-VD (r ≈ 0.7). Over 6 months, glaucoma eyes showed small but statistically significant reductions in RNFL (Δ = −1.04 µm), MD (Δ = −0.10 dB), and PP-VD (Δ = −0.57%), whereas controls remained stable. However, the absolute OCT-A changes were small and largely within the known range of test–retest variability. ANCOVA demonstrated a significant adjusted group effect only for PP-VD (B = −1.22%, 95% CI −1.53 to −0.90; p < 0.001). Conclusions: OCT-A demonstrated clear cross-sectional differences between POAG and controls and strong structure–vascular associations. However, with only two measurements over a 6-month interval, the study cannot distinguish true glaucomatous progression from physiological or device-related variability. Short-term changes should therefore be interpreted cautiously. PP-VD remains the most robust and consistent OCT-A parameter, but larger, longer, and prospectively powered studies are required to validate OCT-A as a reliable biomarker for progression. Full article

(This article belongs to the Special Issue Applications of Optical Coherence Tomography and Optical Coherence Tomography Angiography in Ophthalmology)

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12 pages, 1119 KB

Open AccessArticle

Transcranial Sonographic Characteristics of Substantia Nigra in End-Stage Renal Disease Patients with Restless Legs Syndrome: A Diagnostic Marker Study

by Caishan Wang, Zhoubing Zhan, Changwei Ding, Yingchun Zhang and Weifeng Luo

Diagnostics 2026, 16(1), 41; https://doi.org/10.3390/diagnostics16010041 - 22 Dec 2025

Abstract

Objective: Restless legs syndrome (RLS) is a highly prevalent neurological complication in end-stage renal disease (ESRD) patients. This study aimed to explore the transcranial sonography (TCS) characteristics of the substantia nigra (SN) and brainstem raphe (BR) in ESRD patients with and without [...] Read more.

Objective: Restless legs syndrome (RLS) is a highly prevalent neurological complication in end-stage renal disease (ESRD) patients. This study aimed to explore the transcranial sonography (TCS) characteristics of the substantia nigra (SN) and brainstem raphe (BR) in ESRD patients with and without RLS and to evaluate the diagnostic value of SN echogenicity for ESRD-related RLS. Methods: A total of 65 ESRD patients (45 with RLS [ESRD + RLS] and 20 without RLS [ESRD − RLS]) from the dialysis center and 30 age- and gender-matched healthy controls (NC) from the health management center were enrolled between January 2017 and December 2022. All participants underwent TCS to measure the bilateral SN echogenic area, and the total SN echogenic area (SNsA) was calculated. BR echogenicity was assessed using a semiquantitative scale. Receiver operating characteristic (ROC) curves were plotted to determine the optimal SNsA cutoff for diagnosing ESRD + RLS. Results: The SNsA in the ESRD + RLS group [0.15 (0.13–0.22) cm²] was significantly smaller than that in the ESRD − RLS group [0.27 (0.23–0.31) cm²] and the NC group [0.27 (0.22–0.30) cm²] (both p < 0.001). ROC curve analysis showed that SNsA had the highest diagnostic efficacy for ESRD + RLS, with an area under the curve (AUROC) of 0.823 (95% confidence interval [CI]: 0.722–0.924). At a cutoff of 0.22 cm², SNsA yielded a sensitivity of 85.0%, specificity of 73.3%, accuracy of 76.92%, positive predictive value (PPV) of 58.6%, and negative predictive value (NPV) of 91.7%. The prevalence of BR hypoechogenicity was significantly higher in ESRD + RLS (33.33%) and ESRD − RLS (35.00%) groups than in the NC group (10.00%) (both p < 0.05), but no difference was observed between the two ESRD subgroups (p > 0.05). No significant differences in third ventricle (TV) width or bilateral middle cerebral artery peak systolic velocity (MCA-PSV) were found among the three groups (all p > 0.05). Conclusions: ESRD + RLS patients exhibit significant SN hypoechogenicity compared with ESRD − RLS patients and healthy controls. SNsA with a cutoff of 0.22 cm² serves as a reliable imaging biomarker for diagnosing ESRD + RLS, and TCS is a valuable noninvasive tool to assist clinical decision-making in this population. Full article

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

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12 pages, 1619 KB

Open AccessArticle

Real-World Outcomes of Immediate Femoral Sheath Removal After Emergency Embolization in the Age of Ultrasound-Guided Device-Assisted Vascular Closure

by Terrence Hui, Akshay Kohli, Ross Copping, Hannah Ireland, Shady Osman, Bryan Barry, Jules Catt and Glen Schlaphoff

Diagnostics 2026, 16(1), 40; https://doi.org/10.3390/diagnostics16010040 - 22 Dec 2025

Abstract

Background/Objectives: Emergency arterial embolization is a life-saving procedure typically performed via femoral access. This study evaluated the safety and efficacy of immediate femoral sheath removal following emergency embolization. Methods: A retrospective cohort study was conducted at a Level 1 trauma center [...] Read more.

Background/Objectives: Emergency arterial embolization is a life-saving procedure typically performed via femoral access. This study evaluated the safety and efficacy of immediate femoral sheath removal following emergency embolization. Methods: A retrospective cohort study was conducted at a Level 1 trauma center (January 2022–May 2025). Adult patients undergoing emergency embolization with immediate sheath removal were included. Endpoints were reintervention (repeat embolization within 7 days) and access site complications. Multivariate logistic regression identified independent predictors of outcomes. Results: A total of 322 emergency embolization procedures in 299 patients were included. The most common indication was gastrointestinal hemorrhage (45.7%). Vascular closure devices (VCDs) were used in 92.5% of cases. The re-intervention rate was 4.0% (13/322). The overall access site complication rate was 6.2% (20/322), with a major complication rate of 0.9% (3/322). On univariate analysis, pre-procedural platelet level ≤ 80 × 10⁹/L (p = 0.034) and INR > 1.5 (p = 0.034) were significantly associated with an increased risk of complications. On multivariate analysis, pre-procedural platelets ≤ 80 × 10⁹/L was the strongest independent predictor of access site complications (OR 7.28, 95% CI 1.51–35.12; p = 0.013). Choice of vascular closure device was an independent predictor for both reintervention and complications (p < 0.05), likely reflecting bias. Conclusions: Immediate femoral sheath removal following emergency embolization is safe for most patients. However, thrombocytopenia is a significant risk factor for access site complications. A risk-stratified approach with consideration for delayed sheath removal is warranted for patients with platelet counts ≤ 80 × 10⁹/L. Full article

(This article belongs to the Special Issue Advancements in Interventional Radiology Techniques in Vascular and Extravascular Diseases)

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10 pages, 225 KB

Open AccessArticle

A Critical Assessment of Antenatal Monitoring for Fetal Well-Being in Down Syndrome Pregnancies

by Juliet C. Bishop, Angie C. Jelin, Ahizechukwu C. Eke, Christine B. Hertenstein, Amanda Jones, Clark T. Johnson and Karin Blakemore

Diagnostics 2026, 16(1), 39; https://doi.org/10.3390/diagnostics16010039 - 22 Dec 2025

Abstract

Background/Objectives: The antenatal management of Down syndrome (DS) is difficult as it is associated with a high risk for in utero fetal demise (IUFD) with a paucity of literature to guide antenatal surveillance. Avoidance of preterm delivery in the DS fetus, so commonly [...] Read more.

Background/Objectives: The antenatal management of Down syndrome (DS) is difficult as it is associated with a high risk for in utero fetal demise (IUFD) with a paucity of literature to guide antenatal surveillance. Avoidance of preterm delivery in the DS fetus, so commonly affected by anomalies, compounds the dichotomy of achieving term delivery while balancing against the risk for IUFD as gestational age advances. Higher-performing tests are needed to predict, and, thus, hopefully prevent, both preterm delivery and fetal mortality. Our study was undertaken to evaluate the performance metrics of current antenatal surveillance parameters that might suggest an increased risk for IUFD. Methods: We studied a retrospective cohort of all continuing pregnancies with a cytogenetically confirmed DS fetus between 2009 and 2019 at a single institution. Cases were investigated for abnormalities in fetal growth, anatomy, UA Doppler, and amniotic fluid volume to analyze their interrelationships and their association with the primary outcome, IUFD. Nonstress testing (NST) and biophysical profile data as available were also reviewed for analysis on each case. Maternal demographic data were also collected. Results: A total of 41 DS pregnancies at >20 weeks gestation were included. Eight (19.5%) resulted in IUFD, while thirty-three (80.5%) resulted in live birth. Between these groups, there was no significant difference in the incidence of fetal structural anomalies. FGR was present in 8/41 fetuses or 19.5% of all cases. FGR was present in 1 of 8 (12.5%) IUFD cases and 7 of 33 (21.2%) live births (p = 0.50). Thus, notably, 87.5% (7/8) of the IUFDs occurred in the absence of FGR. Furthermore, 1/8 (12.5%) FGR cases resulted in IUFD vs. 7/33 (21.2%) of non-FGR cases (p = 0.50). In DS fetuses after 24 weeks gestation, UA Doppler abnormalities developed in 75% of FGR cases (6/8) and in 64.5% of normally grown cases (20/31) (p = 0.33). Abnormal UA Dopplers were noted in 83.3% of IUFD and in 84.8% of liveborn cases (p = 0.34). Eleven of thirty-three live births, however, underwent iatrogenic delivery secondary to worsening fetal surveillance, including ten with worsening UA Doppler indices. There was an increased frequency of abnormal NST in the IUFD group (66.7% vs. 23.8%), although this difference did not reach statistical significance. Polyhydramnios was more frequent in the IUFD group (62.5% vs. 16.1%, p = 0.04). Conclusions: Aside from polyhydramnios, no fetal surveillance parameter demonstrated an association with IUFD that reached statistical significance. A majority of fetuses with DS are normally grown and demonstrate abnormal UA Doppler indices in the absence of FGR. Within our cohort, a substantial number of liveborn deliveries were prompted following worsening UA Dopplers. Both polyhydramnios and UA Doppler indices are worthy of further investigation to inform clinically useful fetal surveillance strategies in DS. Full article

(This article belongs to the Special Issue Game-Changing Concepts in Reproductive Health)

15 pages, 966 KB

Open AccessArticle

Long-Term Cardiovascular and Mortality Risk in Patients with Pre-Existing Arrhythmia Post-SARS-CoV-2 Infection

by Suhani Pahuja, Roham Hadidchi, Janhavi Tonge, Sonya Henry and Tim Q. Duong

Diagnostics 2026, 16(1), 38; https://doi.org/10.3390/diagnostics16010038 - 22 Dec 2025

Abstract

Background/Objectives: Individuals with arrhythmia who survived COVID-19 could be susceptible to long-term cardiovascular complications and clinical outcomes. Methods: We performed a retrospective cohort study of adults with a history of arrhythmia in the Montefiore Health System (1 January 2016–17 August 2024). COVID-19 status [...] Read more.

Background/Objectives: Individuals with arrhythmia who survived COVID-19 could be susceptible to long-term cardiovascular complications and clinical outcomes. Methods: We performed a retrospective cohort study of adults with a history of arrhythmia in the Montefiore Health System (1 January 2016–17 August 2024). COVID-19 status was determined by a positive or negative polymerase-chain-reaction test. Outcomes included all-cause mortality, first-time myocardial infarction (MI), heart failure (HF), ischemic or hemorrhagic stroke, and major adverse cardiovascular events (MACE: defined as MI, HF, stroke, or death) > 30 days post-index date. Cox proportional hazards and Fine–Gray competing risk models, adjusted for demographic, clinical, socioeconomic, and COVID-19 vaccination variables, were employed. The association of outcomes with blood biomarkers taken at time of infection were also assessed in hospitalized COVID-19 patients. Results: Among the 6830 arrhythmia patients, 985 were hospitalized for COVID-19, 1591 were not hospitalized for COVID-19, and 4254 did not have COVID-19. Patients hospitalized for COVID-19 had a higher risk of all-cause mortality (adjusted hazard ratio = 2.90, 95% confidence-interval [2.08, 4.04]), first-time MI, HF, and MACE compared to controls without COVID-19. No increased risk was observed among non-hospitalized COVID-19-positive patients compared to controls, except for all-cause mortality. Older age, male sex, Medicaid, and significant comorbidities were associated with the risk of MACE. Elevated levels of creatinine, lactate dehydrogenase, D-dimer, neutrophil-to-lymphocyte ratio, low hemoglobin, and low left ventricular ejection fraction during infection were associated with higher future MACE risk. Conclusions. In individuals with arrhythmia, severe COVID-19 is associated with increased long-term risks of mortality and new-onset cardiovascular complications, while mild infection with mortality risk. These findings highlight the need for long-term cardiovascular monitoring in this population. Full article

(This article belongs to the Special Issue Diagnosis and Prognosis of Heart Disease, 2nd Edition)

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