Diagnostics

17 pages, 766 KiB

Open AccessArticle

Influence of Graft Type on Muscle Contractile Dynamics After ACL Reconstruction: A 9-Month Tensiomyographic Follow-Up

by Georges Kakavas, Florian Forelli, Yoann Demangeot, Vasileios Korakakis, Nikolaos Malliaropoulos and Nicola Maffulli

Diagnostics 2025, 15(15), 1920; https://doi.org/10.3390/diagnostics15151920 (registering DOI) - 30 Jul 2025

Abstract

Background: Persistent neuromuscular deficits following anterior cruciate ligament reconstruction (ACLR) are frequently attributed to arthrogenic muscle inhibition (AMI). The type of autologous graft used may influence the trajectory of neuromuscular recovery. Objective: To investigate the influence of graft type—bone–patellar tendon–bone (BPTB), [...] Read more.

Background: Persistent neuromuscular deficits following anterior cruciate ligament reconstruction (ACLR) are frequently attributed to arthrogenic muscle inhibition (AMI). The type of autologous graft used may influence the trajectory of neuromuscular recovery. Objective: To investigate the influence of graft type—bone–patellar tendon–bone (BPTB), hamstring tendon (HT), and quadriceps tendon (QT)—on the contractile properties of periarticular knee muscles over a 9-month post-operative period. Hypothesis: Each graft type would result in distinct recovery patterns of muscle contractility, as measured by tensiomyography (TMG). Methods: Thirty-one patients undergoing ACLR with BPTB (n = 8), HT (n = 12), or QT (n = 11) autografts were evaluated at 3, 6, and 9 months post-operatively. TMG was used to measure contraction time (Tc) and maximal displacement (Dm) in the rectus femoris, vastus medialis, vastus lateralis, and biceps femoris. Results: Significant within-group improvements in Tc and Dm were observed across all graft types from 3 to 9 months (Tc: p < 0.001 to p = 0.02; Dm: p < 0.001 to p = 0.01). The QT group showed the most pronounced Tc reduction in RF (from 30.16 ± 2.4 ms to 15.44 ± 1.6 ms, p < 0.001) and VM (from 31.05 ± 2.6 ms to 18.65 ± 1.8 ms, p = 0.004). In contrast, HT grafts demonstrated limited Tc recovery in BF between 6 and 9 months compared to BPTB and QT (p < 0.001), indicating a stagnation phase. BPTB exhibited persistent bilateral deficits in both quadriceps and BF at 9 months. Conclusions: Autograft type significantly influences neuromuscular recovery patterns after ACLR. TMG enables objective, muscle-specific monitoring of contractile dynamics and may support future individualized rehabilitation strategies. Full article

(This article belongs to the Special Issue Diagnosis and Management of Sports Medicine)

14 pages, 3600 KiB

Open AccessArticle

Performance of Large Language Models in Recognizing Brain MRI Sequences: A Comparative Analysis of ChatGPT-4o, Claude 4 Opus, and Gemini 2.5 Pro

by Ali Salbas and Rasit Eren Buyuktoka

Diagnostics 2025, 15(15), 1919; https://doi.org/10.3390/diagnostics15151919 - 30 Jul 2025

Abstract

Background/Objectives: Multimodal large language models (LLMs) are increasingly used in radiology. However, their ability to recognize fundamental imaging features, including modality, anatomical region, imaging plane, contrast-enhancement status, and particularly specific magnetic resonance imaging (MRI) sequences, remains underexplored. This study aims to evaluate [...] Read more.

Background/Objectives: Multimodal large language models (LLMs) are increasingly used in radiology. However, their ability to recognize fundamental imaging features, including modality, anatomical region, imaging plane, contrast-enhancement status, and particularly specific magnetic resonance imaging (MRI) sequences, remains underexplored. This study aims to evaluate and compare the performance of three advanced multimodal LLMs (ChatGPT-4o, Claude 4 Opus, and Gemini 2.5 Pro) in classifying brain MRI sequences. Methods: A total of 130 brain MRI images from adult patients without pathological findings were used, representing 13 standard MRI series. Models were tested using zero-shot prompts for identifying modality, anatomical region, imaging plane, contrast-enhancement status, and MRI sequence. Accuracy was calculated, and differences among models were analyzed using Cochran’s Q test and McNemar test with Bonferroni correction. Results: ChatGPT-4o and Gemini 2.5 Pro achieved 100% accuracy in identifying the imaging plane and 98.46% in identifying contrast-enhancement status. MRI sequence classification accuracy was 97.7% for ChatGPT-4o, 93.1% for Gemini 2.5 Pro, and 73.1% for Claude 4 Opus (p < 0.001). The most frequent misclassifications involved fluid-attenuated inversion recovery (FLAIR) sequences, often misclassified as T1-weighted or diffusion-weighted sequences. Claude 4 Opus showed lower accuracy in susceptibility-weighted imaging (SWI) and apparent diffusion coefficient (ADC) sequences. Gemini 2.5 Pro exhibited occasional hallucinations, including irrelevant clinical details such as “hypoglycemia” and “Susac syndrome.” Conclusions: Multimodal LLMs demonstrate high accuracy in basic MRI recognition tasks but vary significantly in specific sequence classification tasks. Hallucinations emphasize caution in clinical use, underlining the need for validation, transparency, and expert oversight. Full article

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

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14 pages, 565 KiB

Open AccessArticle

Saliva Has High Sensitivity and Specificity for Detecting SARS-CoV-2 Compared to Nasal Swabs but Exhibits Different Viral Dynamics from Days of Symptom Onset

by Tor W. Jensen, Rebecca L. Smith and Joseph T. Walsh

Diagnostics 2025, 15(15), 1918; https://doi.org/10.3390/diagnostics15151918 (registering DOI) - 30 Jul 2025

Abstract

Background/Objectives: Saliva as a diagnostic medium for COVID-19 requires fewer resources to collect and is more readily adopted across a range of testers. Our study compared an Emergency Use Authorized direct saliva-to-RT-qPCR test against an FDA-authorized nasal swab RT-qPCR assay for participants [...] Read more.

Background/Objectives: Saliva as a diagnostic medium for COVID-19 requires fewer resources to collect and is more readily adopted across a range of testers. Our study compared an Emergency Use Authorized direct saliva-to-RT-qPCR test against an FDA-authorized nasal swab RT-qPCR assay for participants who reported symptoms of respiratory infection. Methods: We analyzed 737 symptomatic participants who self-selected to test at either a community testing facility or a walk-in clinic due to respiratory symptoms and provided matched saliva and nasal swab samples. Samples were collected between March and September of 2023, both before and after the declared end of the public health emergency. Results: A total of 120 participants tested positive in at least one of the tests. For participants testing in the first 5 days of reported symptoms, the saliva test had a 94.0 positive percent agreement (PPA; 95% C.I. 88.9–99.1%) with the nasal test and a 99.0 negative percent agreement (NPA; 95% C.I. 98.1–99.9%). The viral load decreased beyond day 1 of reported symptoms for saliva testing. Viral load increased up to day 4 for nasal swabs and then decreased. The same number of discordant positive samples (five each) occurred for both tests within 5 days of symptoms onset. Conclusions: In the endemic phase of COVID-19 and for development of new tests, testing methods that are less invasive are more likely to be adopted. The results of saliva-based versus nasal swab PCR measurements relative to days of symptom onset are needed to optimize future testing strategies. Full article

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

13 pages, 11739 KiB

Open AccessArticle

DeepVinci: Organ and Tool Segmentation with Edge Supervision and a Densely Multi-Scale Pyramid Module for Robot-Assisted Surgery

by Li-An Tseng, Yuan-Chih Tsai, Meng-Yi Bai, Mei-Fang Li, Yi-Liang Lee, Kai-Jo Chiang, Yu-Chi Wang and Jing-Ming Guo

Diagnostics 2025, 15(15), 1917; https://doi.org/10.3390/diagnostics15151917 (registering DOI) - 30 Jul 2025

Abstract

Background: Automated surgical navigation can be separated into three stages: (1) organ identification and localization, (2) identification of the organs requiring further surgery, and (3) automated planning of the operation path and steps. With its ideal visual and operating system, the da [...] Read more.

Background: Automated surgical navigation can be separated into three stages: (1) organ identification and localization, (2) identification of the organs requiring further surgery, and (3) automated planning of the operation path and steps. With its ideal visual and operating system, the da Vinci surgical system provides a promising platform for automated surgical navigation. This study focuses on the first step in automated surgical navigation by identifying organs in gynecological surgery. Methods: Due to the difficulty of collecting da Vinci gynecological endoscopy data, we propose DeepVinci, a novel end-to-end high-performance encoder–decoder network based on convolutional neural networks (CNNs) for pixel-level organ semantic segmentation. Specifically, to overcome the drawback of a limited field of view, we incorporate a densely multi-scale pyramid module and feature fusion module, which can also enhance the global context information. In addition, the system integrates an edge supervision network to refine the segmented results on the decoding side. Results: Experimental results show that DeepVinci can achieve state-of-the-art accuracy, obtaining dice similarity coefficient and mean pixel accuracy values of 0.684 and 0.700, respectively. Conclusions: The proposed DeepVinci network presents a practical and competitive semantic segmentation solution for da Vinci gynecological surgery. Full article

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

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31 pages, 526 KiB

Open AccessReview

Unlocking the Potential of Liquid Biopsy: A Paradigm Shift in Endometrial Cancer Care

by Nannan Gui, Chalong Cheewakriangkrai, Parunya Chaiyawat and Sasimol Udomruk

Diagnostics 2025, 15(15), 1916; https://doi.org/10.3390/diagnostics15151916 - 30 Jul 2025

Abstract

Endometrial cancer is one of the most prevalent gynecologic malignancies in developed countries, with its incidence steadily increasing each year. Early diagnosis is crucial for a favorable prognosis; however, certain patients experience recurrence and distant metastasis after surgery, similar to advanced cancer patients, [...] Read more.

Endometrial cancer is one of the most prevalent gynecologic malignancies in developed countries, with its incidence steadily increasing each year. Early diagnosis is crucial for a favorable prognosis; however, certain patients experience recurrence and distant metastasis after surgery, similar to advanced cancer patients, with limited treatment options. Therefore, effective strategies for early screening, diagnosis, predicting local recurrence, and guiding rapid treatment interventions are essential for improving survival rates and prognosis. Liquid biopsy, a method known for being non-invasive, safe, and effective, has attracted widespread attention for cancer diagnosis and treatment. Although its clinical application in endometrial cancer is less established than in other cancers, research on biomarkers using liquid biopsy in endometrial cancer patients is currently in progress. This review examines the latest advancements in non-invasive biomarkers identified through liquid biopsy and provides a comprehensive overview of their clinical applications in endometrial cancer. Additionally, it discusses the challenges and future prospects of liquid biopsy, offering valuable insights into the diagnosis and personalized treatment of endometrial cancer. Full article

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

21 pages, 732 KiB

Open AccessReview

Clonal Hematopoiesis of Intermediate Potential in Atrial Fibrillation: A Critical View of Current Knowledge as a Springboard for Future Research

by Elena Chatzikalil, Dimitris Asvestas, Stylianos Tzeis and Elena E. Solomou

Diagnostics 2025, 15(15), 1915; https://doi.org/10.3390/diagnostics15151915 - 30 Jul 2025

Abstract

Clonal hematopoiesis of intermediate potential (CHIP) is the presence of a clonally expanded hematopoietic stem cell because of a mutation in individuals without evidence of hematologic malignancy, dysplasia, or cytopenia. Interestingly, CHIP is associated with a two-fold increase in cardiovascular risk, independently of [...] Read more.

Clonal hematopoiesis of intermediate potential (CHIP) is the presence of a clonally expanded hematopoietic stem cell because of a mutation in individuals without evidence of hematologic malignancy, dysplasia, or cytopenia. Interestingly, CHIP is associated with a two-fold increase in cardiovascular risk, independently of traditional risk factors. Recent studies using deep-targeted sequencing have revealed that CHIP mutations, primarily TET2 and DNMT3A, present a higher incidence in patients with AF compared to healthy controls. Moreover, the presence of the aforementioned mutations is positively correlated with the progression and the severity of the AF clinical course. Regarding the predisposition of AF, it has been proven that TET2 and ASXL1 mutations, and not DNMT3A mutation, are associated with higher interleukin-6 (IL-6) levels. IL-6 levels, being indices of cardiac remodeling, predispose to an elevated risk for AF in healthy subjects. Currently conducted research has focused on elaborating the mechanisms driving the association between AF and CHIP and on the evaluation of potential interventions to reduce the risk of AF development. The aims of our review are (i) to summarize published evidence regarding the presence of CHIP mutations as a contributor to AF severity and predisposition, and (ii) to highlight the potential benefits of investigating the correlations between CHIP and AF for AF-diagnosed patients. Full article

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

40 pages, 3463 KiB

Open AccessReview

Machine Learning-Powered Smart Healthcare Systems in the Era of Big Data: Applications, Diagnostic Insights, Challenges, and Ethical Implications

by Sita Rani, Raman Kumar, B. S. Panda, Rajender Kumar, Nafaa Farhan Muften, Mayada Ahmed Abass and Jasmina Lozanović

Diagnostics 2025, 15(15), 1914; https://doi.org/10.3390/diagnostics15151914 - 30 Jul 2025

Abstract

Healthcare data rapidly increases, and patients seek customized, effective healthcare services. Big data and machine learning (ML) enabled smart healthcare systems hold revolutionary potential. Unlike previous reviews that separately address AI or big data, this work synthesizes their convergence through real-world case studies, [...] Read more.

Healthcare data rapidly increases, and patients seek customized, effective healthcare services. Big data and machine learning (ML) enabled smart healthcare systems hold revolutionary potential. Unlike previous reviews that separately address AI or big data, this work synthesizes their convergence through real-world case studies, cross-domain ML applications, and a critical discussion on ethical integration in smart diagnostics. The review focuses on the role of big data analysis and ML towards better diagnosis, improved efficiency of operations, and individualized care for patients. It explores the principal challenges of data heterogeneity, privacy, computational complexity, and advanced methods such as federated learning (FL) and edge computing. Applications in real-world settings, such as disease prediction, medical imaging, drug discovery, and remote monitoring, illustrate how ML methods, such as deep learning (DL) and natural language processing (NLP), enhance clinical decision-making. A comparison of ML models highlights their value in dealing with large and heterogeneous healthcare datasets. In addition, the use of nascent technologies such as wearables and Internet of Medical Things (IoMT) is examined for their role in supporting real-time data-driven delivery of healthcare. The paper emphasizes the pragmatic application of intelligent systems by highlighting case studies that reflect up to 95% diagnostic accuracy and cost savings. The review ends with future directions that seek to develop scalable, ethical, and interpretable AI-powered healthcare systems. It bridges the gap between ML algorithms and smart diagnostics, offering critical perspectives for clinicians, data scientists, and policymakers. Full article

(This article belongs to the Special Issue Machine-Learning-Based Disease Diagnosis and Prediction)

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15 pages, 747 KiB

Open AccessArticle

Comparative Analysis of LLMs in Dry Eye Syndrome Healthcare Information

by Gloria Wu, Hrishi Paliath-Pathiyal, Obaid Khan and Margaret C. Wang

Diagnostics 2025, 15(15), 1913; https://doi.org/10.3390/diagnostics15151913 - 30 Jul 2025

Abstract

Background/Objective: Dry eye syndrome affects 16 million Americans with USD 52 billion in annual healthcare costs. With large language models (LLMs) increasingly used for healthcare information, understanding their performance in delivering equitable dry eye guidance across diverse populations is critical. This study aims [...] Read more.

Background/Objective: Dry eye syndrome affects 16 million Americans with USD 52 billion in annual healthcare costs. With large language models (LLMs) increasingly used for healthcare information, understanding their performance in delivering equitable dry eye guidance across diverse populations is critical. This study aims to evaluate and compare five major LLMs (Grok, ChatGPT, Gemini, Claude.ai, and Meta AI) regarding dry eye syndrome information delivery across different demographic groups. Methods: LLMs were queried using standardized prompts simulating a 62-year-old patient with dry eye symptoms across four demographic categories (White, Black, East Asian, and Hispanic males and females). Responses were analyzed for word count, readability, cultural sensitivity scores (0–3 scale), keyword coverage, and response times. Results: Significant variations existed across LLMs. Word counts ranged from 32 to 346 words, with Gemini being the most comprehensive (653.8 ± 96.2 words) and Claude.ai being the most concise (207.6 ± 10.8 words). Cultural sensitivity scores revealed Grok demonstrated highest awareness for minority populations (scoring 3 for Black and Hispanic demographics), while Meta AI showed minimal cultural tailoring (0.5 ± 0.5). All models recommended specialist consultation, but medical term coverage varied significantly. Response times ranged from 7.41 s (Meta AI) to 25.32 s (Gemini). Conclusions: While all LLMs provided appropriate referral recommendations, substantial disparities exist in cultural sensitivity, content depth, and information delivery across demographic groups. No LLM consistently addressed the full spectrum of dry eye causes across all demographics. These findings underscore the importance for physician oversight and standardization in AI-generated healthcare information to ensure equitable access and prevent care delays. Full article

(This article belongs to the Special Issue Artificial Intelligence Application in Cornea and External Diseases)

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20 pages, 2055 KiB

Open AccessArticle

Tailored Magnetic Fe₃O₄-Based Core–Shell Nanoparticles Coated with TiO₂ and SiO₂ via Co-Precipitation: Structure–Property Correlation for Medical Imaging Applications

by Elena Emanuela Herbei, Daniela Laura Buruiana, Alina Crina Muresan, Viorica Ghisman, Nicoleta Lucica Bogatu, Vasile Basliu, Claudiu-Ionut Vasile and Lucian Barbu-Tudoran

Diagnostics 2025, 15(15), 1912; https://doi.org/10.3390/diagnostics15151912 - 30 Jul 2025

Abstract

Background/Objectives: Magnetic nanoparticles, particularly iron oxide-based materials, such as magnetite (Fe₃O₄), have gained significant attention as contrast agents in medical imaging This study aimsto syntheze and characterize Fe₃O₄-based core–shell nanostructures, including Fe₃O₄@TiO₂ and Fe₃O₄@SiO₂, and to evaluate their potential [...] Read more.

Background/Objectives: Magnetic nanoparticles, particularly iron oxide-based materials, such as magnetite (Fe₃O₄), have gained significant attention as contrast agents in medical imaging This study aimsto syntheze and characterize Fe₃O₄-based core–shell nanostructures, including Fe₃O₄@TiO₂ and Fe₃O₄@SiO₂, and to evaluate their potential as tunable contrast agents for diagnostic imaging. Methods: Fe₃O₄, Fe₃O₄@TiO₂, and Fe₃O₄@SiO₂ nanoparticles were synthesized via co-precipitation at varying temperatures from iron salt precursors. Fourier transform infrared spectroscopy (FTIR) was used to confirm the presence of Fe–O bonds, while X-ray diffraction (XRD) was employed to determine the crystalline phases and estimate average crystallite sizes. Morphological analysis and particle size distribution were assessed by scanning electron microscopy with energy-dispersive X-ray spectroscopy (SEM-EDX) and transmission electron microscopy (TEM). Magnetic properties were investigated using vibrating sample magnetometry (VSM). Results: FTIR spectra exhibited characteristic Fe–O vibrations at 543 cm⁻¹ and 555 cm⁻¹, indicating the formation of magnetite. XRD patterns confirmed a dominant cubic magnetite phase, with the presence of rutile TiO₂ and stishovite SiO₂ in the coated samples. The average crystallite sizes ranged from 24 to 95 nm. SEM and TEM analyses revealed particle sizes between 5 and 150 nm with well-defined core–shell morphologies. VSM measurements showed saturation magnetization (Ms) values ranging from 40 to 70 emu/g, depending on the synthesis temperature and shell composition. The highest Ms value was obtained for uncoated Fe₃O₄ synthesized at 94 °C. Conclusions: The synthesized Fe₃O₄-based core–shell nanomaterials exhibit desirable structural, morphological, and magnetic properties for use as contrast agents. Their tunable magnetic response and nanoscale dimensions make them promising candidates for advanced diagnostic imaging applications. Full article

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

20 pages, 3217 KiB

Open AccessArticle

Microbiome of the Proximal Small Intestine in Patients with Acute Pancreatitis

by Vladimir V. Kiselev, Stanislav I. Koshechkin, Alexey V. Kurenkov, Vera E. Odintsova, Maria S. Zhigalova, Alekxandr V. Tyakht, Sergey S. Petrikov, Petr A. Yartsev and Ilya V. Dmitriev

Diagnostics 2025, 15(15), 1911; https://doi.org/10.3390/diagnostics15151911 - 30 Jul 2025

Abstract

Currently, due to the complexity of obtaining samples, specific features of laboratory processing and analysis of the results, there is a lack of data on the microbial signature of the small intestine in healthy and diseased states of the upper gastrointestinal tract. Objective: [...] Read more.

Currently, due to the complexity of obtaining samples, specific features of laboratory processing and analysis of the results, there is a lack of data on the microbial signature of the small intestine in healthy and diseased states of the upper gastrointestinal tract. Objective: To investigate the characteristics of the small intestinal microbiome in acute pancreatitis of varying severity and to identify correlations with clinical factors. Methods: This study included 30 patients with acute pancreatitis of varying severity treated between 1 January 2019 and 31 December 2021. The composition of the microbiota was analyzed by metagenomic sequencing of the 16S rRNA gene from jejunal samples. Results: The mortality rate in the study group was 23.3%. The small intestinal microbiome was dominated by Streptococcus (median relative abundance 19.2%, interquartile range 6.4–35.1%), Veillonella (3.4%; 0.6–7%), Granulicatella (2.7%; 0.6–5%), Fusobacterium (2.2%; 0.3–5.9%), Prevotella (1.5%; 0.3–8%), Haemophilus (0.9%; 0.2–10%), Gemella (0.8%; 0.2–4.3%), and Lactobacillus (0.2%; 0.1–0.9%). More severe disease was associated with decreased abundance of Neisseria mucosa, Parvimonas micra, and Megasphaera micronuciformis. In contrast, the relative abundance of the genera Streptococcus (species S. rubneri/parasanguinis/australis), Actinomyces, and several genera within the family Enterobacteriaceae was higher in these patients. Conclusions: The state of the microbiota has important prognostic value and correlates with the duration from the onset of the pain syndrome to the time of receiving qualified care in the hospital. Full article

(This article belongs to the Special Issue Advances in the Diagnosis of Infectious Diseases and Microorganisms: 2nd Edition)

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5 pages, 628 KiB

Open AccessInteresting Images

Infrared Photography: A Novel Diagnostic Approach for Ocular Surface Abnormalities Due to Vitamin A Deficiency

by Hideki Fukuoka and Chie Sotozono

Diagnostics 2025, 15(15), 1910; https://doi.org/10.3390/diagnostics15151910 - 30 Jul 2025

Abstract

Vitamin A deficiency (VAD) remains a significant cause of preventable blindness worldwide, with ocular surface changes representing early manifestations that require prompt recognition and treatment. Conventional examination methods are capable of detecting advanced changes; however, subtle conjunctival abnormalities may be overlooked, potentially delaying [...] Read more.

Vitamin A deficiency (VAD) remains a significant cause of preventable blindness worldwide, with ocular surface changes representing early manifestations that require prompt recognition and treatment. Conventional examination methods are capable of detecting advanced changes; however, subtle conjunctival abnormalities may be overlooked, potentially delaying the administration of appropriate interventions. We herein present the case of a 5-year-old Japanese boy with severe VAD due to selective eating patterns. This case demonstrates the utility of infrared photography as a novel diagnostic approach for detecting and monitoring conjunctival surface abnormalities. The patient exhibited symptoms including corneal ulcers, night blindness, and reduced visual acuity. Furthermore, blood tests revealed undetectable levels of vitamin A (5 IU/dL), despite relatively normal physical growth parameters. Conventional slit-lamp examination revealed characteristic sandpaper-like conjunctival changes. However, infrared photography (700–900 nm wavelength) revealed distinct abnormal patterns of conjunctival surface folds and keratinization that were not fully appreciated on a routine examination. Following high-dose vitamin A supplementation (4000 IU/day), complete resolution of ocular abnormalities was achieved within 2 months, with infrared imaging objectively documenting treatment response and normalization of conjunctival surface patterns. This case underscores the potential for severe VAD in developed countries, particularly in the context of dietary restrictions, thereby underscoring the significance of a comprehensive dietary history and a meticulous ocular examination. Infrared photography provides a number of advantages, including the capacity for non-invasive assessment, enhanced visualization of subtle changes, objective monitoring of treatment response, and cost-effectiveness due to the use of readily available equipment. This technique represents an underutilized diagnostic modality with particular promise for screening programs and clinical monitoring of VAD-related ocular manifestations, potentially preventing irreversible visual loss through early detection and intervention. Full article

(This article belongs to the Collection Interesting Images)

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21 pages, 799 KiB

Open AccessReview

The Molecular Diagnosis of Invasive Fungal Diseases with a Focus on PCR

by Lottie Brown, Mario Cruciani, Charles Oliver Morton, Alexandre Alanio, Rosemary A. Barnes, J. Peter Donnelly, Ferry Hagen, Rebecca Gorton, Michaela Lackner, Juergen Loeffler, Laurence Millon, Riina Rautemaa-Richardson and P. Lewis White

Diagnostics 2025, 15(15), 1909; https://doi.org/10.3390/diagnostics15151909 - 30 Jul 2025

Abstract

Background: Polymerase chain reaction (PCR) is highly sensitive and specific for the rapid diagnosis of invasive fungal disease (IFD) but is not yet widely implemented due to concerns regarding limited standardisation between assays, the lack of commercial options and the absence of [...] Read more.

Background: Polymerase chain reaction (PCR) is highly sensitive and specific for the rapid diagnosis of invasive fungal disease (IFD) but is not yet widely implemented due to concerns regarding limited standardisation between assays, the lack of commercial options and the absence of clear guidance on interpreting results. Objectives and Methods: This review provides an update on technical and clinical aspects of PCR for the diagnosis of the most pertinent fungal pathogens, including Aspergillus, Candida, Pneumocystis jirovecii, Mucorales spp., and endemic mycoses. Summary: Recent meta-analyses have demonstrated that quantitative PCR (qPCR) offers high sensitivity for diagnosing IFD, surpassing conventional microscopy, culture and most serological tests. The reported specificity of qPCR is likely underestimated due to comparison with imperfect reference standards with variable sensitivity. Although the very low limit of detection of qPCR can generate false positive results due to procedural contamination or patient colonisation (particularly in pulmonary specimens), the rates are comparable to those observed for biomarker testing. When interpreting qPCR results, it is essential to consider the pre-test probability, determined by the patient population, host factors, clinical presentation and risk factors. For patients with low to moderate pre-test probability, the use of sensitive molecular tests, often in conjunction with serological testing or biomarkers, can effectively exclude IFD when all tests return negative results, reducing the need for empirical antifungal therapy. Conversely, for patients with high pre-test probability and clinical features of IFD, qPCR testing on invasive specimens from the site of infection (such as tissue or bronchoalveolar lavage fluid) can confidently rule in the disease. The development of next-generation sequencing methods to detect fungal infection has the potential to enhance the diagnosis of IFD, but standardisation and optimisation are essential, with improved accessibility underpinning clinical utility. Full article

(This article belongs to the Special Issue Advances in Diagnostic and Therapeutic Strategies for Infectious Diseases)

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22 pages, 2677 KiB

Open AccessArticle

Prevalence of Temporomandibular Disorder Symptoms Among Dental Students at the Faculty of Dental Medicine in Iași: A Self-Reported Study Based on DC/TMD Criteria

by Eugenia Larisa Tarevici, Oana Tanculescu, Alina Mihaela Apostu, Sorina Mihaela Solomon, Alice-Teodora Rotaru-Costin, Adrian Doloca, Petronela Bodnar, Vlad Stefan Proca, Alice-Arina Ciocan-Pendefunda, Monica Tatarciuc, Valeriu Fala and Marina Cristina Iuliana Iordache

Diagnostics 2025, 15(15), 1908; https://doi.org/10.3390/diagnostics15151908 - 30 Jul 2025

Abstract

Temporomandibular disorders (TMDs) encompass a heterogeneous group of musculoskeletal and neuromuscular conditions affecting the temporomandibular joint (TMJ) and masticatory system. Due to academic stress and parafunctional habits, dental students may be particularly vulnerable to TMD. Objective: To determine the prevalence of TMD symptoms [...] Read more.

Temporomandibular disorders (TMDs) encompass a heterogeneous group of musculoskeletal and neuromuscular conditions affecting the temporomandibular joint (TMJ) and masticatory system. Due to academic stress and parafunctional habits, dental students may be particularly vulnerable to TMD. Objective: To determine the prevalence of TMD symptoms and their psychosocial and functional correlates among students at the Faculty of Dental Medicine, UMPh Iasi, Romania, using the diagnostic criteria for TMD (DC/TMD) self-report axis and axis II instruments. Methods: In this cross-sectional survey, 356 volunteer students (66.0% female; mean age, 22.9 ± 3.6 years) out of a total population of 1874 completed an online DC/TMD–based questionnaire. Axis I assessed orofacial pain, joint noises, and mandibular locking. Axis II instruments included the Graded Chronic Pain Scale (GCPS), Jaw Functional Limitation Scale (JFLS-20), Patient Health Questionnaire (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and Oral Behaviors Checklist (OBC). Descriptive statistics summarized frequencies, means, and standard deviations; χ² tests and t-tests compared subgroups by sex; Pearson correlations explored relationships among continuous measures (α = 0.05). Results: A total of 5% of respondents reported orofacial pain in the past 30 days; 41.6% observed TMJ noises; 19.7% experienced locking episodes. Mean JFLS score was 28.3 ± 30.5, with 4.8% scoring > 80 (severe limitation). Mean PHQ-9 was 5.96 ± 5.37 (mild depression); 15.5% scored ≥ 10. Mean GAD-7 was 5.20 ± 4.95 (mild anxiety); 16.0% scored ≥ 10. Mean OBC score was 12.3 ± 8.5; 30.1% scored ≥ 16, indicating frequent parafunctional habits. Symptom prevalence was similar by sex, except temporal headache (43.4% females vs. 24.3% males; p = 0.0008). Females reported higher mean scores for pain intensity (2.09 vs. 1.55; p = 0.0013), JFLS (32.5 vs. 18.0; p < 0.001), PHQ-9 (6.43 vs. 5.16; p = 0.048), and OBC (13.9 vs. 9.7; p = 0.0014). Strong correlation was observed between PHQ-9 and GAD-7 (r = 0.74; p < 0.001); moderate correlations were observed between pain intensity and PHQ-9 (r = 0.31) or GAD-7 (r = 0.30), between JFLS and pain intensity (r = 0.33), and between OBC and PHQ-9 (r = 0.39) (all p < 0.001). Conclusions: Nearly half of dental students reported TMD symptoms, with appreciable functional limitation and psychosocial impact. Parafunctional behaviors and psychological distress were significantly associated with pain and dysfunction. These findings underscore the need for early screening, stress-management interventions, and interdisciplinary care strategies in the dental student population. Full article

(This article belongs to the Special Issue Recent Updates on the Diagnosis of Dental and Oral Diseases, Second Edition)

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17 pages, 2337 KiB

Open AccessSystematic Review

Optical Coherence Tomography-Guided vs. Angiography-Guided Percutaneous Coronary Intervention for Complex Coronary Lesions: A Systematic Review and Meta-Analysis

by Muhammad Hamza Shuja, Muhammad Ahmed, Ramish Hannat, Laiba Khurram, Hamza Ali Hasnain Sheikh, Syed Hasan Shuja, Adarsh Raja, Jawad Ahmed, Kriti Soni, Shariq Ahmad Wani, Aman Goyal, Bala Pushparaji, Ali Hasan, Raheel Ahmed and Hritvik Jain

Diagnostics 2025, 15(15), 1907; https://doi.org/10.3390/diagnostics15151907 - 30 Jul 2025

Abstract

Background: Despite advances in coronary artery disease (CAD) treatment, challenges persist, particularly in complex lesions. While percutaneous coronary intervention (PCI) is widely used, its outcomes can be affected by complications like restenosis. Optical coherence tomography (OCT), offering higher-resolution imaging than angiography, shows [...] Read more.

Background: Despite advances in coronary artery disease (CAD) treatment, challenges persist, particularly in complex lesions. While percutaneous coronary intervention (PCI) is widely used, its outcomes can be affected by complications like restenosis. Optical coherence tomography (OCT), offering higher-resolution imaging than angiography, shows promise in guiding PCI. However, meta-analytical comparisons between OCT-guided and angiography-guided PCI remain limited. Methods: Databases, including PubMed, Scopus, Cochrane Library, and ClinicalTrials.gov, were queried through May 2025 to identify randomized controlled trials (RCTs) comparing OCT-guided PCI with angiography-guided PCI. Data were pooled using risk ratios (RRs) and mean difference (MD) with 95% confidence intervals (CIs) in a random-effects model. Results: Five RCTs involving 5737 patients (OCT: 2738 and angiography: 2999) were included. On pooled analysis, OCT-guided PCI was associated with a notable reduction in major adverse cardiovascular event (MACE) (RR: 0.71, p = 0.0001), cardiac mortality (RR: 0.43, p = 0.003), target lesion revascularization (TLR) (RR: 0.53, p = 0.007), and stroke (RR: 0.17, p = 0.02), compared to angiography-guided PCI. No significant differences were noted for all-cause mortality and myocardial infarction. Conclusions: In patients with complex coronary lesions, OCT-guided PCI reduces the risk of MACE, cardiac mortality, TLR, and stroke, compared to angiography-guided PCI only. This study supports incorporating advanced imaging techniques like OCT to improve clinical outcomes, especially in complex PCIs. Full article

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

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30 pages, 1403 KiB

Open AccessReview

Role of Interleukins in Type 1 and Type 2 Diabetes

by Roha Asif, Ammara Khalid, Tolga Mercantepe, Aleksandra Klisic, Sana Rafaqat, Saira Rafaqat and Filiz Mercantepe

Diagnostics 2025, 15(15), 1906; https://doi.org/10.3390/diagnostics15151906 - 30 Jul 2025

Abstract

Background: Despite distinct etiologies, type 1 diabetes (T1D) and type 2 diabetes (T2D) share chronic inflammation as a core feature. Interleukins, key immune mediators, play important yet still not fully understood roles in the development and complications of both conditions. Objective: [...] Read more.

Background: Despite distinct etiologies, type 1 diabetes (T1D) and type 2 diabetes (T2D) share chronic inflammation as a core feature. Interleukins, key immune mediators, play important yet still not fully understood roles in the development and complications of both conditions. Objective: This narrative review aims to provide a comprehensive and critical synthesis of current evidence on the role of key interleukins in T1D and T2D, highlighting their immunological functions, genetic associations, clinical correlations, and translational potential. Methods: A targeted literature search was conducted in PubMed, Google Scholar, and ScienceDirect up to January 2025, focusing on English-language clinical and experimental studies involving interleukins and their relevance to T1D and T2D. Reference lists were manually screened for additional sources. Interleukins (ILs) were reviewed individually to assess their immunobiology, disease specificity, and biomarker or therapeutic value. Findings: Pro-inflammatory cytokines such as IL-1β, IL-6, and IL-17 contribute to islet inflammation, insulin resistance, and microvascular damage in both T1D and T2D. Anti-inflammatory mediators including IL-4, IL-10, and IL-13 exhibit protective effects but vary in expression across disease stages. Less-characterized interleukins such as IL-3, IL-5, IL-9, and IL-27 demonstrate dual or context-dependent roles, particularly in shaping immune tolerance and tissue-specific complications such as nephropathy and neuropathy. Polymorphisms in IL-10 and IL-6 genes further suggest genetic contributions to interleukin dysregulation and metabolic dysfunction. Despite promising insights, translational gaps persist due to overreliance on preclinical models and limited longitudinal clinical data. Conclusions: Interleukins represent a mechanistic bridge linking immune dysregulation to metabolic derangements in both T1D and T2D. While their diagnostic and therapeutic potential is increasingly recognized, future research must address current limitations through isoform-specific targeting, context-aware interventions, and validation in large-scale, human cohorts. A unified interleukin-based framework may ultimately advance personalized strategies for diabetes prevention and treatment. Full article

(This article belongs to the Special Issue Clinical Prognostic and Predictive Biomarkers, Third Edition)

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23 pages, 931 KiB

Open AccessReview

Neutrophils and Platelets as Key Players in the Pathogenesis of ANCA-Associated Vasculitis and Potential Sources of Disease Activity Biomarkers

by Anna Drynda, Marcin Surmiak, Stanisława Bazan-Socha, Katarzyna Wawrzycka-Adamczyk, Mariusz Korkosz, Jacek Musiał and Krzysztof Wójcik

Diagnostics 2025, 15(15), 1905; https://doi.org/10.3390/diagnostics15151905 - 29 Jul 2025

Abstract

Anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) is a heterogeneous group of small-vessel vasculitides, characterized by the presence of antibodies binding to myeloperoxidase (MPO) and proteinase-3 (PR3) found in neutrophil granules. Apart from being the target of ANCA, neutrophils actively contribute to the vicious [...] Read more.

Anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) is a heterogeneous group of small-vessel vasculitides, characterized by the presence of antibodies binding to myeloperoxidase (MPO) and proteinase-3 (PR3) found in neutrophil granules. Apart from being the target of ANCA, neutrophils actively contribute to the vicious cycle of inflammation and vascular damage in AAV. On the other hand, platelets have recently been recognized as essential for thrombosis and as inflammatory effectors that collaborate with neutrophils, reinforcing the generation of reactive oxygen species (ROS) and the formation of neutrophil extracellular traps (NETs) in those diseases. Neutrophils exhibit morphological and functional heterogeneity in AAV, reflecting the complexity of their contribution to disease pathogenesis. Since long-term immunosuppression may be related to serious infections and malignancies, there is an urgent need for reliable biomarkers of disease activity to optimize the management of AAV. This review summarizes the current understanding of the role of neutrophils and platelets in the pathogenesis of granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), focusing on their crosstalk, and highlights the potential for identifying novel biomarkers relevant for predicting the disease course and its relapses. Full article

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

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15 pages, 4667 KiB

Open AccessArticle

Longitudinal High-Resolution Imaging of Retinal Sequelae of a Choroidal Nevus

by Kaitlyn A. Sapoznik, Stephen A. Burns, Todd D. Peabody, Lucie Sawides, Brittany R. Walker and Thomas J. Gast

Diagnostics 2025, 15(15), 1904; https://doi.org/10.3390/diagnostics15151904 - 29 Jul 2025

Abstract

Background: Choroidal nevi are common, benign tumors. These tumors rarely cause adverse retinal sequalae, but when they do, they can lead to disruption of the outer retina and vision loss. In this paper, we used high-resolution retinal imaging modalities, optical coherence tomography [...] Read more.

Background: Choroidal nevi are common, benign tumors. These tumors rarely cause adverse retinal sequalae, but when they do, they can lead to disruption of the outer retina and vision loss. In this paper, we used high-resolution retinal imaging modalities, optical coherence tomography (OCT) and adaptive optics scanning laser ophthalmoscopy (AOSLO), to longitudinally monitor retinal sequelae of a submacular choroidal nevus. Methods: A 31-year-old female with a high-risk choroidal nevus resulting in subretinal fluid (SRF) and a 30-year-old control subject were longitudinally imaged with AOSLO and OCT in this study over 18 and 22 months. Regions of interest (ROI) including the macular region (where SRF was present) and the site of laser photocoagulation were imaged repeatedly over time. The depth of SRF in a discrete ROI was quantified with OCT and AOSLO images were assessed for visualization of photoreceptors and retinal pigmented epithelium (RPE). Cell-like structures that infiltrated the site of laser photocoagulation were measured and their count was assessed over time. In the control subject, images were assessed for RPE visualization and the presence and stability of cell-like structures. Results: We demonstrate that AOSLO can be used to assess cellular-level changes at small ROIs in the retina over time. We show the response of the retina to SRF and laser photocoagulation. We demonstrate that the RPE can be visualized when SRF is present, which does not appear to depend on the height of retinal elevation. We also demonstrate that cell-like structures, presumably immune cells, are present within and adjacent to areas of SRF on both OCT and AOSLO, and that similar cell-like structures infiltrate areas of retinal laser photocoagulation. Conclusions: Our study demonstrates that dynamic, cellular-level retinal responses to SRF and laser photocoagulation can be monitored over time with AOSLO in living humans. Many retinal conditions exhibit similar retinal findings and laser photocoagulation is also indicated in numerous retinal conditions. AOSLO imaging may provide future opportunities to better understand the clinical implications of such responses in vivo. Full article

(This article belongs to the Special Issue High-Resolution Retinal Imaging: Hot Topics and Recent Developments)

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25 pages, 4837 KiB

Open AccessArticle

Multimodal Computational Approach for Forecasting Cardiovascular Aging Based on Immune and Clinical–Biochemical Parameters

by Madina Suleimenova, Kuat Abzaliyev, Ainur Manapova, Madina Mansurova, Symbat Abzaliyeva, Saule Doskozhayeva, Akbota Bugibayeva, Almagul Kurmanova, Diana Sundetova, Merey Abdykassymova and Ulzhas Sagalbayeva

Diagnostics 2025, 15(15), 1903; https://doi.org/10.3390/diagnostics15151903 - 29 Jul 2025

Abstract

Background: This study presents an innovative approach to cardiovascular disease (CVD) risk prediction based on a comprehensive analysis of clinical, immunological and biochemical markers using mathematical modelling and machine learning methods. Baseline data include indices of humoral and cellular immunity (CD59, CD16, [...] Read more.

Background: This study presents an innovative approach to cardiovascular disease (CVD) risk prediction based on a comprehensive analysis of clinical, immunological and biochemical markers using mathematical modelling and machine learning methods. Baseline data include indices of humoral and cellular immunity (CD59, CD16, IL-10, CD14, CD19, CD8, CD4, etc.), cytokines and markers of cardiovascular disease, inflammatory markers (TNF, GM-CSF, CRP), growth and angiogenesis factors (VEGF, PGF), proteins involved in apoptosis and cytotoxicity (perforin, CD95), as well as indices of liver function, kidney function, oxidative stress and heart failure (albumin, cystatin C, N-terminal pro B-type natriuretic peptide (NT-proBNP), superoxide dismutase (SOD), C-reactive protein (CRP), cholinesterase (ChE), cholesterol, and glomerular filtration rate (GFR)). Clinical and behavioural risk factors were also considered: arterial hypertension (AH), previous myocardial infarction (PICS), aortocoronary bypass surgery (CABG) and/or stenting, coronary heart disease (CHD), atrial fibrillation (AF), atrioventricular block (AB block), and diabetes mellitus (DM), as well as lifestyle (smoking, alcohol consumption, physical activity level), education, and body mass index (BMI). Methods: The study included 52 patients aged 65 years and older. Based on the clinical, biochemical and immunological data obtained, a model for predicting the risk of premature cardiovascular aging was developed using mathematical modelling and machine learning methods. The aim of the study was to develop a predictive model allowing for the early detection of predisposition to the development of CVDs and their complications. Numerical methods of mathematical modelling, including Runge–Kutta, Adams–Bashforth and backward-directed Euler methods, were used to solve the prediction problem, which made it possible to describe the dynamics of changes in biomarkers and patients’ condition over time with high accuracy. Results: HLA-DR (50%), CD14 (41%) and CD16 (38%) showed the highest association with aging processes. BMI was correlated with placental growth factor (37%). The glomerular filtration rate was positively associated with physical activity (47%), whereas SOD activity was negatively correlated with it (48%), reflecting a decline in antioxidant defence. Conclusions: The obtained results allow for improving the accuracy of cardiovascular risk prediction, and form personalised recommendations for the prevention and correction of its development. Full article

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

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10 pages, 1153 KiB

Open AccessArticle

Clinical Trends and Hospital Mortality of Transjugular Intrahepatic Portosystemic Shunt (TIPS) in Germany: A Descriptive Analysis Between 2019 and 2023

by Sven H. Loosen, Christian Weigel, Anselm Kunstein, Peter Minko, Gerald Antoch, Johannes G. Bode, Tom Luedde, Christoph Roderburg and Karel Kostev

Diagnostics 2025, 15(15), 1902; https://doi.org/10.3390/diagnostics15151902 - 29 Jul 2025

Abstract

Background/Objectives: The transjugular intrahepatic portosystemic shunt (TIPS) is an established treatment for complications of portal hypertension in patients with liver cirrhosis. While its use has increased and indications have broadened in recent years, recent comprehensive data on patient characteristics, trends, and in-hospital mortality [...] Read more.

Background/Objectives: The transjugular intrahepatic portosystemic shunt (TIPS) is an established treatment for complications of portal hypertension in patients with liver cirrhosis. While its use has increased and indications have broadened in recent years, recent comprehensive data on patient characteristics, trends, and in-hospital mortality in Germany are lacking. This study aimed to evaluate current clinical patterns and mortality outcomes associated with TIPS. Methods: This nationwide cross-sectional study used anonymized hospital data from the German InEK database between 2019 and 2023. TIPS procedures were identified using relevant OPS codes. Patient demographics, liver cirrhosis stage (Child–Pugh), hepatic encephalopathy grade, comorbid conditions, and in-hospital mortality were analyzed descriptively. Analyses were conducted using SAS 9.4. Results: A total of 12,905 TIPS procedures were documented. Annual case numbers rose from 2180 in 2019 to 2954 in 2023. Most patients were male (66.3%) and aged 60–74 years. Ascites (68.6%) was the most frequent associated diagnosis, followed by variceal bleeding (16.4%) and hepatorenal syndrome (14.9%). The average hospital stay decreased from 19.6 to 16.8 days. Overall in-hospital mortality was 8.5%, increasing with age (13.0% in ≥75 years), Child–Pugh C cirrhosis (14.9%), PCCL grade 4 (17.6%), hepatorenal syndrome (16.7%), and grade 4 hepatic encephalopathy (56.1%). Conclusions: TIPS usage in Germany has increased over the past five years, with a shift toward earlier disease stages. Higher in-hospital mortality in clinically complex patients underscores the importance of careful patient selection and tailored management strategies in high-risk groups. Full article

(This article belongs to the Special Issue Diagnosis and Management of Liver Diseases, Third Edition)

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