Diagnostics

13 pages, 469 KiB

Open AccessArticle

Overlap Syndrome of Primary Sjögren Syndrome with Antineutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis Based on the American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) Criteria

by Hyun Joon Choi, Jang Woo Ha, Jason Jungsik Song, Yong-Beom Park and Sang-Won Lee

Diagnostics 2025, 15(9), 1099; https://doi.org/10.3390/diagnostics15091099 - 25 Apr 2025

Abstract

Background/Objectives: The overlap syndrome of primary Sjögren syndrome (pSS) with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) (OvSD/pSS/AAV) has been reported in other studies. This study applied the new criteria for AAV proposed by the American College of Rheumatology/European Alliance of Associations for [...] Read more.

Background/Objectives: The overlap syndrome of primary Sjögren syndrome (pSS) with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) (OvSD/pSS/AAV) has been reported in other studies. This study applied the new criteria for AAV proposed by the American College of Rheumatology/European Alliance of Associations for Rheumatology in 2022 (the ACR/EULAR criteria) to patients with pSS presenting signs and symptoms suggestive of small- and medium-vessel vasculitis. It also investigated the overall frequency of OvSD/pSS/AAV and the major contributing factors to its reclassification. Methods: This study included 116 patients with pSS from March 2005 to December 2020, according to the inclusion criteria, and defined signs and symptoms suggestive of small- or medium-vessel vasculitides as lung parenchymal lesions supporting AAV, peripheral neuropathy, and suspected renal vasculitis. The classification could be made when the total scores for microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) are ≥5 points and the eosinophilic GPA (EGPA) score is ≥6 points. Results: The median age of the patients was 56.0 years, and 101 patients (87.1%) were women. In total, 95, 12, and 37 patients had lung parenchymal lesions supporting AAV, peripheral neuropathy, and suspected renal vasculitis, respectively. According to the ACR/EULAR criteria for AAV, 35 of 116 (30.2%) patients were reclassified as having OvSD/pSS/AAV. Among these 35 patients, 4 were reclassified as having both OvSD/pSS/MPA and OvSD/pSS/GPA and 1 as having both OvSD/pSS/MPA and OvSD/pSS/EGPA simultaneously. The major contributing factor to the reclassification of OvSD/pSS/AAV was ANCA positivity. Conclusions: The overall frequency of the reclassification of OvSD/pSS/AAV was 30.2% in pSS patients presenting signs and symptoms suggestive of small- and medium-vessel vasculitis. Its likelihood increased according to ANCA positivity. Full article

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

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15 pages, 1918 KiB

Open AccessArticle

A Breast Cancer Polygenic Risk Score Validation in 15,490 Brazilians Using Exome Sequencing

by Flávia Eichemberger Rius, Rodrigo Santa Cruz Guindalini, Danilo Viana, Júlia Salomão, Laila Gallo, Renata Freitas, Cláudia Bertolacini, Lucas Taniguti, Danilo Imparato, Flávia Antunes, Gabriel Sousa, Renan Achjian, Eric Fukuyama, Cleandra Gregório, Iuri Ventura, Juliana Gomes, Nathália Taniguti, Simone Maistro, José Eduardo Krieger, Yonglan Zheng, Dezheng Huo, Olufunmilayo I. Olopade, Maria Aparecida Azevedo Koike Folgueira and David Schlesinger Show full author list Hide full author list

Diagnostics 2025, 15(9), 1098; https://doi.org/10.3390/diagnostics15091098 - 25 Apr 2025

Abstract

Background/Objectives: Brazil has a highly admixed population. Polygenic risk scores (PRSs) have mostly been developed from European population studies, and their application to other populations is challenging. To assess the use of PRS for breast cancer (BC) risk in Brazil, we evaluated [...] Read more.

Background/Objectives: Brazil has a highly admixed population. Polygenic risk scores (PRSs) have mostly been developed from European population studies, and their application to other populations is challenging. To assess the use of PRS for breast cancer (BC) risk in Brazil, we evaluated four PRSs in the Brazilian population. Methods: We analyzed a Brazilian cohort composed of 6206 women with a history of breast cancer and 8878 unphenotyped adults as controls. Genomic variants were imputed from exomes, and scores were calculated for all samples. Results: After individuals with known pathogenic or likely pathogenic variants in BRCA1, BRCA2, PALB2, PTEN, or TP53 genes, and first-degree relatives of the probands were excluded, 5598 cases and 8767 controls remained. Four PRS models were compared, and PRS₃₈₂₀ achieved the best performance, with an odds ratio (OR) of 1.43 per standard deviation increase (p value < 0.001) and an OR of 1.88 (p value < 0.001) for the top decile. PRS₃₈₂₀ also performed well for different ancestry groups: East Asian majority (OR 1.59, p value 0.004), Non-European majority (OR 1.45, p value < 0.001), and European majority (OR 1.43, p value < 0.001). Conclusions: Among the different PRSs, PRS₃₁₃ and PRS₃₈₂₀ could be validated in our Brazilian cohort, with the latter exhibiting the best performance. While further clinical studies are necessary to guide clinical practice, this work represents an important step toward improving BC precision medicine in Brazil. Full article

(This article belongs to the Special Issue Advances in Cancer Pathology and Diagnosis)

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11 pages, 329 KiB

Open AccessArticle

Serum P-Cresyl Sulfate Levels Correlate with Peripheral Arterial Disease in Hypertensive Patients

by Yahn-Bor Chern, Jen-Pi Tsai, Bang-Gee Hsu, Chin-Hung Liu and Ji-Hung Wang

Diagnostics 2025, 15(9), 1097; https://doi.org/10.3390/diagnostics15091097 - 25 Apr 2025

Abstract

Background/Objectives: p-Cresyl sulfate (PCS) is implicated in inflammation, oxidative stress and vascular dysfunction. Hypertension is a major risk factor for peripheral arterial disease (PAD), which is linked to increased mortality in patients with hypertension. This study aimed to evaluate the association between [...] Read more.

Background/Objectives: p-Cresyl sulfate (PCS) is implicated in inflammation, oxidative stress and vascular dysfunction. Hypertension is a major risk factor for peripheral arterial disease (PAD), which is linked to increased mortality in patients with hypertension. This study aimed to evaluate the association between serum PCS levels and PAD in hypertension cases. Methods: We analyzed fasting blood samples and clinical data from 105 patients with hypertension in a cardiovascular outpatient clinic. Serum PCS levels were quantified using high-performance liquid chromatography–mass spectrometry. Ankle–brachial index (ABI) was measured using an automated oscillometric device; ABI < 0.9 indicated PAD. Results: A total of 24 patients (22.9%) had PAD. The PAD group had a higher prevalence of diabetes mellitus (p = 0.026), elevated serum C-reactive protein (CRP) levels (p < 0.001) and increased PCS levels (p = 0.002) than the normal ABI group. Multivariate logistic regression showed that PCS (odds ratio [OR]: 1.154, 95% confidence interval [CI]: 1.013–1.315, p = 0.031) and CRP (per 0.1 mg/dL increase, OR: 1.649, 95% CI: 1.138–2.389, p = 0.008) were independently associated with PAD. According to Spearman’s correlation analysis, log-transformed PCS (log-PCS) levels negatively correlated with left or right ABI (p = 0.001 and p = 0.004, respectively) and estimated glomerular filtration rate (p = 0.001) but positively correlated with log-CRP (p = 0.024). Conclusions: Elevated serum PCS and CRP levels are significantly associated with PAD in patients with hypertension, suggesting the potential role of PCS in PAD pathogenesis. Full article

(This article belongs to the Special Issue Liquid Chromatography–Mass Spectrometry (LC-MS) in the Clinical Laboratory)

16 pages, 1736 KiB

Open AccessArticle

Machine Learning-Based Non-Invasive Prediction of Metabolic Dysfunction-Associated Steatohepatitis in Obese Patients: A Retrospective Study

by Jie Chen, Bo Zhang, Yong Cheng, Yuanchen Jia and Biao Zhou

Diagnostics 2025, 15(9), 1096; https://doi.org/10.3390/diagnostics15091096 - 25 Apr 2025

Abstract

Objectives: We aimed to develop and validate machine learning (ML) models that integrate clinical and laboratory data for the non-invasive prediction of metabolic dysfunction-associated steatohepatitis (MASH) in an obese population. Methods: In this retrospective study, clinical and laboratory data were collected [...] Read more.

Objectives: We aimed to develop and validate machine learning (ML) models that integrate clinical and laboratory data for the non-invasive prediction of metabolic dysfunction-associated steatohepatitis (MASH) in an obese population. Methods: In this retrospective study, clinical and laboratory data were collected from obese patients undergoing bariatric surgery. The cohort was divided using stratified random sampling, and optimal features were selected with SHapley Additive exPlanations (SHAP). Various ML models, including K-nearest neighbors, linear support vector machine, radial basis function support vector machine, Gaussian process, random forest, multilayer perceptron, adaptive boosting, and naïve Bayes, were developed through cross-validation and hyperparameter tuning. Diagnostic performance was assessed via the area under the curve (AUC) in both training and validation sets. Results: A total of 558 patients were analyzed, with 390 in the training set and 168 in the validation set. In the training cohort, the median age was 35 years, the median body mass index (BMI) was 39.8 kg/m², 39.0% were male, 37.9% had diabetes mellitus, and 62.8% were diagnosed with MASH. The validation cohort had a median age of 34.1 years, a median BMI of 42.5 kg/m², 41.7% male, 32.7% with diabetes, and 39.9% with MASH. Among the models, the random forest achieved the highest performance among the models with AUC values of 0.94 in the training set and 0.88 in the validation set. The Gaussian process model attained an AUC of 0.97 in the training cohort but 0.79 in the validation cohort, while the other models achieved AUC values ranging from 0.63 to 0.88 in the training cohort and 0.62 to 0.75 in the validation set. Conclusions: ML models, particularly the random forest, effectively predict MASH using readily available data, offering a promising non-invasive alternative to conventional serological scoring. Prospective studies and external validations are needed to further establish clinical utility. Full article

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

17 pages, 694 KiB

Open AccessArticle

Clinical and Electrophysiological Predictors of Isthmus Dependency in Atrial Flutter

by Lyuboslav Katov, Sonja Reiländer, Alyssa Schlarb, Federica Diofano, Deniz Aktolga, Yannick Teumer, Carlo Bothner, Wolfgang Rottbauer and Karolina Weinmann-Emhardt

Diagnostics 2025, 15(9), 1095; https://doi.org/10.3390/diagnostics15091095 - 25 Apr 2025

Abstract

Background: Atrial flutter (AFL) is a macro-reentrant tachycardia classified as cavotricuspid isthmus (CTI)-dependent or non-CTI-dependent based on its reliance on the CTI for conduction. CTI dependence can present as type I ECG (sawtooth flutter waves in inferior leads and positive P-waves in [...] Read more.

Background: Atrial flutter (AFL) is a macro-reentrant tachycardia classified as cavotricuspid isthmus (CTI)-dependent or non-CTI-dependent based on its reliance on the CTI for conduction. CTI dependence can present as type I ECG (sawtooth flutter waves in inferior leads and positive P-waves in V1) or type II ECG (absence of these characteristics). This study aimed to identify clinical and electrophysiological parameters to improve CTI dependence prediction in AFL. Methods: Patients at the Ulm University Heart Center between 2010 and 2019 with AFL undergoing electrophysiological studies and ablation were enrolled. Clinical and electrophysiological parameters such as age, gender, prior comorbidities, interventions, and medication use were analyzed. Results: The study included 383 patients, with 70% presenting with type I ECG AFL. CTI dependence was observed in 242 (90.3%) type I ECG patients and 52 (45.2%) type II ECG patients. CTI-dependent AFL patients were younger and had fewer comorbidities. Predictors for CTI dependence in type I ECG included male gender (p = 0.006), absence of beta-blocker use (p = 0.031), no prior atrial fibrillation (p = 0.035), and no prior pulmonary vein isolation (p < 0.001). In type II ECG, predictors for CTI dependence included younger age (p = 0.016), male gender (p = 0.007), absence of arterial hypertension (p = 0.036), and longer atrial cycle length (p < 0.001). Conclusions: Identifying clinical and electrophysiological parameters enhances the ability to predict CTI dependence in AFL, offering valuable insights for tailored diagnostic and therapeutic approaches. Coupling these parameters with ECG findings holds promise for refining prediction accuracy and optimizing patient care. Full article

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

21 pages, 12179 KiB

Open AccessArticle

Identification of PECAM1 as a Prognostic Biomarker for Lung Adenocarcinoma

by Shih-Sen Lin, Pei-Sung Hsu, Ying-Chu Lin, Jie-Yu You, Yung-Leun Shih and Hung-Chih Lai

Diagnostics 2025, 15(9), 1094; https://doi.org/10.3390/diagnostics15091094 - 25 Apr 2025

Abstract

Background: Lung cancer continues to be one of the most fatal malignancies globally. Uncovering differentially expressed genes (DEGs) is crucial for advancing our understanding of tumor mechanisms and discovering new therapeutic targets. This study sought to identify key genes linked to prognosis [...] Read more.

Background: Lung cancer continues to be one of the most fatal malignancies globally. Uncovering differentially expressed genes (DEGs) is crucial for advancing our understanding of tumor mechanisms and discovering new therapeutic targets. This study sought to identify key genes linked to prognosis and immune infiltration in lung cancer through the analysis of public gene expression datasets. Methods: We examined three microarray datasets from the Gene Expression Omnibus (GSE10072, GSE33356, and GSE18842) to detect DEGs between tumor and normal lung tissues. Functional enrichment was performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses to interpret the biological relevance of these genes. Protein–protein interaction (PPI) networks were constructed via STRING and visualized using Cytoscape to screen for central hub genes. The prognostic implications of the hub genes were investigated using Kaplan–Meier Plotter and TIMER2.0 based on data from The Cancer Genome Atlas (TCGA). PECAM1 expression levels and its relationship with immune cell infiltration were further explored using UCSC Xena. Results: A total of 477 DEGs were consistently identified across all three datasets. Among the top 10 down-regulated hub genes, PECAM1 was significantly reduced in tumor tissues. Lower PECAM1 expression was positively associated with better first-progression survival (FPS) in lung cancer patients. This gene was particularly suppressed in lung adenocarcinoma (LUAD) and showed strong correlations with immune cell infiltration. Co-expression analysis revealed that genes linked to PECAM1 are involved in immune-related pathways. Conclusions: Our findings highlight PECAM1 as a potential prognostic biomarker in lung cancer, especially in LUAD. Its association with immune infiltration and patient survival supports its possible utility in early detection and as a candidate for immunotherapy development. Full article

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

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9 pages, 378 KiB

Open AccessArticle

Age-Adjusted Cut-Off Values for Glial Fibrillary Acidic Protein and Ubiquitin Carboxy-Terminal Hydrolase L1 Improve the Diagnostic Accuracy of the Abbott Mild Traumatic Brain Injury Assay

by Ivana Lapić, Dunja Rogić, Matea Bingula, Lea Miklić and Ivan Gornik

Diagnostics 2025, 15(9), 1093; https://doi.org/10.3390/diagnostics15091093 - 25 Apr 2025

Abstract

Objectives: To establish age-adjusted cut-off values for glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) and assess their impact on the diagnostic performance of the mild traumatic brain injury (mTBI) assay. Methods: The study included 175 adult mTBI [...] Read more.

Objectives: To establish age-adjusted cut-off values for glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) and assess their impact on the diagnostic performance of the mild traumatic brain injury (mTBI) assay. Methods: The study included 175 adult mTBI patients presenting at the emergency department (ED) within 12 h from head trauma in whom head CT scan was performed. GFAP and UCH-L1 were measured using chemiluminescence immunoassays on an Abbott analyzer (Abbott Laboratories, USA). Results: Using manufacturer’s defined cut-offs (GFAP < 35 ng/L, UCH-L1 < 400 ng/L), the mTBI assay exhibited diagnostic sensitivity (Se) of 93.1%, specificity (Sp) of 28.8%, negative predictive value (NPV) of 95.5% and a positive predictive value (PPV) of 20.6%. In the subgroup of patients aged under 50, Se and NPV were below 100% (i.e., 75.0% and 92.3%), due to two false negative mTBI results. Age-adjusted cut-offs were defined for three patient groups, ≤49 years, 50–69 years and ≥70 years, and were set to 22.4, 37.0 and 62.3 ng/L for GFAP, and 349.3, 351.6 and 369.0 ng/L for UCH-L1. Using these cut-offs, in all patient groups Se and NPV were 100%, while increased Sp was obtained in patients older than 50 years. Conclusions: Diagnostic Se and NPV can be improved by the use of age-adjusted cut-offs. In this way, the triage protocol for mTBI and head CT scan can be refined, further contributing to the optimization of the diagnostic management of mTBI patients at the ED. Full article

(This article belongs to the Special Issue Emergency Medicine: Diagnostic Insights)

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11 pages, 1776 KiB

Open AccessReview

Unmet Needs of Artificial Intelligence in Small Bowel Capsule Endoscopy

by Stefania Piccirelli, Daniele Salvi, Cecilia Lina Pugliano, Enrico Tettoni, Antonio Facciorusso, Emanuele Rondonotti, Alessandro Mussetto, Lorenzo Fuccio, Paola Cesaro and Cristiano Spada

Diagnostics 2025, 15(9), 1092; https://doi.org/10.3390/diagnostics15091092 - 25 Apr 2025

Abstract

Small bowel capsule endoscopy (SBCE) has emerged in the past two decades as the cornerstone for assessing small bowel disorders, and its use is supported by several guidelines. However, there are several limitations, such as the considerable time required for gastroenterologists to review [...] Read more.

Small bowel capsule endoscopy (SBCE) has emerged in the past two decades as the cornerstone for assessing small bowel disorders, and its use is supported by several guidelines. However, there are several limitations, such as the considerable time required for gastroenterologists to review these videos and reach a diagnosis. To address these limitations, researchers have explored the integration of artificial intelligence in the interpretation of these videos. In our review, we explore the evolving and emerging role of artificial intelligence in SBCE and examine the latest advancements and ongoing studies in these areas, aiming at overcoming current limitations. Full article

(This article belongs to the Special Issue Clinical Impacts and Challenges in Capsule Endoscopy)

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12 pages, 1256 KiB

Open AccessArticle

SARS-CoV-2 Infection Is Associated with an Accelerated eGFR Decline in Kidney Transplant Recipients up to Four Years Post Infection

by Shawn Qiu, Roham Hadidchi, Aditi Vichare, Justin Y. Lu, Wei Hou, Sonya Henry, Enver Akalin and Tim Q. Duong

Diagnostics 2025, 15(9), 1091; https://doi.org/10.3390/diagnostics15091091 - 25 Apr 2025

Abstract

Background/Objectives: Although kidney transplant recipients (KTRs) who are immune-compromised have been shown to be at high risk of adverse acute COVID-19 outcomes (i.e., mortality and critical illness), the long-term outcomes of KTRs with a history of SARS-CoV-2 infection are unknown. We aimed to [...] Read more.

Background/Objectives: Although kidney transplant recipients (KTRs) who are immune-compromised have been shown to be at high risk of adverse acute COVID-19 outcomes (i.e., mortality and critical illness), the long-term outcomes of KTRs with a history of SARS-CoV-2 infection are unknown. We aimed to compare long-term outcomes of KTRs with and without exposure to SARS-CoV-2. Methods: This study retrospectively evaluated 1815 KTRs in the Montefiore Health System from 4 January 2001 to 31 January 2024. The final cohorts consisted of KTRs who survived COVID-19 (n = 510) and matched KTRs without COVID-19 (n = 510, controls). Outcomes were defined as all-cause mortality and changes in estimated glomerular filtration rate (eGFR) and urine protein to creatinine ratio (UPCR) from 30 days up to four years post index date. Kaplan–Meier survival analysis and Cox proportional modeling were performed for mortality. Generalized estimating equations were used to analyze changes in eGFR and UPCR across time. Results: There was no significant group difference in long-term all-cause mortality (adjusted hazard ratio = 0.66, [0.43, 1.01] p = 0.057). eGFR in controls and COVID-19 patients before infection similarly decreased −0.98 units/year [−1.50, −0.46]. By contrast, eGFR declined at a significantly greater rate (−1.80 units/year [−2.45, −1.15]) in KTRs after COVID-19 compared to KTRs without COVID-19. This association was only seen among male and not female KTRs. COVID-19 status was not significantly associated with rate of change in UPCR or acute kidney rejection rate. Conclusions: SARS-CoV-2 infection was associated with an accelerated decline in eGFR up to four years post infection, suggesting potential long-term implications for graft health. These findings underscore the importance of vigilant monitoring and management of kidney function post SARS-CoV-2 infection in this vulnerable population. Full article

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

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14 pages, 1788 KiB

Open AccessReview

Hallmarks of Bacterial Vaginosis

by Diana Cristina Pérez-Ibave, Carlos Horacio Burciaga-Flores, Ximena García-Mejía, Fernando Alcorta-Nuñez, Orlando Solis-Coronado, Moisés González Escamilla, Oscar Vidal-Gutiérrez and María Lourdes Garza-Rodríguez

Diagnostics 2025, 15(9), 1090; https://doi.org/10.3390/diagnostics15091090 - 25 Apr 2025

Abstract

Background: Bacterial vaginosis (BV) is considered the most common cause of vaginal discharge, which is related to several public health issues, such as an increased risk for sexually transmitted infections, pelvic inflammatory disease, pregnancy-related problems such as abortion, stillbirth or premature birth, and [...] Read more.

Background: Bacterial vaginosis (BV) is considered the most common cause of vaginal discharge, which is related to several public health issues, such as an increased risk for sexually transmitted infections, pelvic inflammatory disease, pregnancy-related problems such as abortion, stillbirth or premature birth, and tubal factor infertility. BV is not considered an infection but an imbalance in the vaginal microbiota, characterized by a substitution of the normal Lactobacilli flora by anaerobe. Reducing resistance against infections by several mechanisms, including bacterial homeostasis, stabilization of acid pH, inhibition of pathogens adhesion by polyamine degradation, production of anti-inflammatory molecules, surfactants, and antimicrobial substances like hydrogen peroxide, acids, and bacteriocins. Approximately half of women with BV can experience symptoms, which mainly include vaginal malodor, fishy discharge, stinging sensation, and increased vaginal pH. The treatment of BV is based primarily on promoting Lactobacilli restoration and eliminating dangerous microbiota with antibiotic therapy. However, there is a high rate of recurrence and relapse. Objective: Based on the current literature, this review aims to propose a list of ten BV hallmarks: dysbiosis, inflammation, apoptosis, pH basification, mucosal barrier integrity, pathway activation, epithelial damage, genomic instability, oxidative stress (OS), and metabolic reconfiguration. Conclusions: Understanding the causes of BV and the pathogenicity mechanisms is critical for preventing and improving the current therapeutic management of patients. Full article

(This article belongs to the Special Issue Vulvovaginal Disorders: The Critical Role of Accurate Diagnosis to Effective Management Strategies)

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9 pages, 1502 KiB

Open AccessReview

From Morphology to Gene Expression Profiling in Mycosis Fungoides: Is It Still a Diagnostic Challenge?

by Alessandra Filosa, Gerardo Cazzato, Elisa Bartoli, Elena Antaldi, Federica Giantomassi, Matteo Santoni and Gaia Goteri

Diagnostics 2025, 15(9), 1089; https://doi.org/10.3390/diagnostics15091089 - 25 Apr 2025

Abstract

Background: We herein review the most important clinico-pathological features of mycosis fungoides (MF). These evolving clinico-pathological aspects are paired with innovative therapeutic schemes. Moreover, we indicate cutaneous lymphomas as a new frontier of artificial intelligence application. Methods: We encompass new diagnostic [...] Read more.

Background: We herein review the most important clinico-pathological features of mycosis fungoides (MF). These evolving clinico-pathological aspects are paired with innovative therapeutic schemes. Moreover, we indicate cutaneous lymphomas as a new frontier of artificial intelligence application. Methods: We encompass new diagnostic and prognostic data derived from the recent medical literature describing the possible histological features which could be the targets of deep learning in conjunction with available clinical data. Results: In spite of decades of research, MF diagnosis still represents the most challenging debate from a dermatopathologist’s point of view. Genetic alterations have been identified mainly in late stages of the disease, and their importance for disease initiation is still unclear. The exploration of the genome-wide expression of individual genes in skin samples may be useful in elucidating MF pathogenesis and improving early diagnosis, while artificial intelligence could offer the possibility of searching for biomarkers of disease progression. Conclusions: MF still deserves the name of the ‘great imitator’, both clinically and histopathologically. The goal of summing up all the clinico-pathological information before reaching a final diagnosis is the approach needed to reach diagnostic accuracy, especially in early MF cases. It is advisable to think of the most common clinical presentations, to be aware of the most common histopathological features, and to interpret the results of ancillary studies only in the right clinico-pathological context. Full article

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

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24 pages, 1196 KiB

Open AccessReview

The Global Burden of Obstructive Sleep Apnea

by Giannicola Iannella, Annalisa Pace, Mario Giuseppe Bellizzi, Giuseppe Magliulo, Antonio Greco, Armando De Virgilio, Enrica Croce, Federico Maria Gioacchini, Massimo Re, Andrea Costantino, Manuele Casale, Antonio Moffa, Jerome R. Lechien, Salvatore Cocuzza, Claudio Vicini, Alberto Caranti, Rosario Marchese Aragona, Mario Lentini and Antonino Maniaci

Diagnostics 2025, 15(9), 1088; https://doi.org/10.3390/diagnostics15091088 - 25 Apr 2025

Abstract

This study reviewed the global prevalence, health and socioeconomic impact, and management approaches of obstructive sleep apnea. The narrative review examined three key dimensions: (1) worldwide OSA prevalence across different regions, accounting for variations in diagnostic standards; (2) OSA’s effects on health outcomes [...] Read more.

This study reviewed the global prevalence, health and socioeconomic impact, and management approaches of obstructive sleep apnea. The narrative review examined three key dimensions: (1) worldwide OSA prevalence across different regions, accounting for variations in diagnostic standards; (2) OSA’s effects on health outcomes and socioeconomic conditions across diverse populations and healthcare systems; and (3) current global approaches to OSA diagnosis, treatment, and public health management. Despite advances in diagnosis and treatment, a large proportion of OSA cases remain undiagnosed or inadequately managed. The findings show that untreated OSA significantly increases public safety risks, particularly regarding motor vehicle and occupational accidents, while also creating a substantial pool of patients at high risk for systemic complications with severe impacts on overall health. There is a critical need for increased public awareness, universal screening approaches, and integrated care strategies to address this global health challenge and reduce its considerable socioeconomic burden. Our review uniquely addresses global disparities in OSA prevalence, clarifies the health and socioeconomic impacts that remain underexplored in the current literature, and suggests concrete strategies for public health and clinical management improvement worldwide. Full article

(This article belongs to the Special Issue Advances in Diagnosis and Treatment of Obstructive Sleep Apnea)

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20 pages, 305 KiB

Open AccessReview

Liver Elastography Methods for Diagnosis of De Novo and Recurrent Hepatocellular Carcinoma

by Razvan Cerban, Speranta Iacob, Carmen Ester, Mihaela Ghioca, Mirela Chitul, Razvan Iacob and Liana Gheorghe

Diagnostics 2025, 15(9), 1087; https://doi.org/10.3390/diagnostics15091087 - 25 Apr 2025

Abstract

Hepatocellular carcinoma (HCC), a common consequence of chronic liver disease, ranks among the most prevalent cancers globally and contributes significantly to cancer-related mortality. Liver fibrosis is intimately associated with hepatic function and the likelihood of future HCC occurrence. Despite the fact that liver [...] Read more.

Hepatocellular carcinoma (HCC), a common consequence of chronic liver disease, ranks among the most prevalent cancers globally and contributes significantly to cancer-related mortality. Liver fibrosis is intimately associated with hepatic function and the likelihood of future HCC occurrence. Despite the fact that liver biopsy continues to be the gold standard for diagnosing fibrosis, its utility is hindered by cost and invasiveness, along with patient unease, procedural rejection, and potential adverse effects. Liver elastography has become a leading noninvasive means of assessing tissue stiffness with considerable diagnostic precision. Malignant tumors generally exhibit higher cellularity in comparison to benign ones, resulting in increased stiffness. Elastography techniques capitalize on alterations in tissue elasticity stemming from specific pathological or physiological processes. Technological innovations, such as advanced ultrasound imaging and artificial intelligence (AI)-integrated systems, are paving the way for enhanced diagnostic accuracy and risk prediction. Recent research underscores the potential of elastography in managing HCC patients, presenting novel clinical applications, including prediction of HCC development, differentiation between malignant and benign liver lesions, evaluating treatment response, and forecasting recurrence post-treatment, though certain findings remain contentious. Therefore, this review aims to sum up the latest advancements in liver elastography for HCC patients, outlining its applications while addressing existing limitations and avenues for future progress. Full article

(This article belongs to the Special Issue Advancements in the Diagnosis and Management of Liver Disease and Liver Transplantation)

11 pages, 565 KiB

Open AccessArticle

Pleural Fluid Biomarkers of Pediatric Parapneumonic Effusion

by Jose D. Santotoribio, David Nuñez-Jurado, Jose L. Rubio-Prieto, Juan M. Guerrero, Juan Corral-Pérez and Juan J. Fernández-Alba

Diagnostics 2025, 15(9), 1086; https://doi.org/10.3390/diagnostics15091086 - 24 Apr 2025

Abstract

Background/Objectives: Parapneumonic pleural effusion (PPE) secondary to community-acquired pneumonia is the most common cause of pediatric pleural effusion. This study aimed to evaluate the pleural fluid characteristics of pediatric patients with PPE and to compare biomarkers between infants (1–12 months) and children (1–14 [...] Read more.

Background/Objectives: Parapneumonic pleural effusion (PPE) secondary to community-acquired pneumonia is the most common cause of pediatric pleural effusion. This study aimed to evaluate the pleural fluid characteristics of pediatric patients with PPE and to compare biomarkers between infants (1–12 months) and children (1–14 years). Methods: Fifty-four pediatric patients (14 infants and 40 children) with PPE were included. Pleural fluid samples were analyzed for white blood cell (WBC) count, glucose, total protein, lactate dehydrogenase (LDH), adenosine deaminase (ADA), and pH levels. Differences between age groups and correlations between age and pleural fluid biomarkers were assessed. Results: Most pediatric PPE cases exhibited biochemical characteristics consistent with pleural exudate: WBC > 1000 cells/µL, total protein > 3 g/dL, LDH > 200 U/L. Infants showed a predominance of mononuclear WBC, while children exhibited a predominance of polymorphonuclear WBC. Glucose levels were higher, and total protein levels were lower in infants compared to children. Age was positively correlated with polymorphonuclear WBC percentage (rho = 0.509, p < 0.001) and protein levels (rho = 0.622, p < 0.001), whereas glucose levels were negatively correlated with age (rho = −0.274, p = 0.043). Conclusions: Age-specific differences in pleural fluid biomarkers were observed in pediatric patients with PPE, suggesting a more robust and acute inflammatory response in children compared to infants. These findings underscore the importance of considering age-related variations in the inflammatory response when diagnosing and managing PPE in pediatric populations. Full article

(This article belongs to the Section Clinical Laboratory Medicine)

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14 pages, 13972 KiB

Open AccessArticle

Rapid and Efficient Screening of Helicobacter pylori in Gastric Samples Stained with Warthin–Starry Using Deep Learning

by José Aneiros-Fernández, Pedro Montero Pavón, Natalia García Gómez, Rosa María Palo Prian, Ismael Sánchez García, Ana Isabel Romero Ortiz, Rodrigo López Castro, César Casado-Sánchez, Víctor Sánchez Turrión, Antonio Luna and Manuel Álvaro Berbís

Diagnostics 2025, 15(9), 1085; https://doi.org/10.3390/diagnostics15091085 - 24 Apr 2025

Abstract

Background/Objectives: Helicobacter pylori is a major risk factor for gastric cancer. The incidence and prevalence of the pathogen are increasing worldwide, urging novel approaches to reduce detection turnaround times. H. pylori diagnosis relies on histological examination of gastric biopsies, but interobserver variability considerably [...] Read more.

Background/Objectives: Helicobacter pylori is a major risk factor for gastric cancer. The incidence and prevalence of the pathogen are increasing worldwide, urging novel approaches to reduce detection turnaround times. H. pylori diagnosis relies on histological examination of gastric biopsies, but interobserver variability considerably impacts its identification. We present an algorithm combining a feature pyramid network and a ResNet architecture for automatic and rapid H. pylori detection in digitized Warthin–Starry-stained gastric biopsies. Methods: Whole-slide images were segmented into manually annotated smaller patches and segments containing stomach tissue were analyzed for the presence of Gram-negative bacteria. Patches classified as positive were examined to confirm the presence/absence of bacteria in contact with the gastric epithelial surface (H. pylori). Results: The algorithm exhibited 0.923 average precision and 0.982 average recall. The conducted efficiency study demonstrated that algorithm utilization significantly decreased (p < 0.001) diagnostic turnaround times for all participants (two pathologists, a pathology resident, a pathology technician, and a biotechnologist), observing an 88.13–91.76% time reduction. Implementation of the algorithm also improved diagnostic accuracy for the resident, technician, and biotechnologist, indicating that the tool remarkably supports less experienced personnel. Conclusions: We believe that the incorporation of our algorithm into pathology workflows will help standardize diagnostic protocols and drastically reduce H. pylori diagnostic turnaround times. Full article

(This article belongs to the Special Issue Application of Artificial Intelligence in Gastrointestinal Disease)

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22 pages, 1313 KiB

Open AccessArticle

Mucoscopic Features of Oral Lichen Planus: A Retrospective Comparative Study with Inflammatory Mimickers

by Mihaela Paula Toader, Oana Mihaela Condurache Hritcu, Cristina Colac Botoc, Antonia Elena Hutanu, Catalina Anca Munteanu, Roxana Paraschiva Ciobanu, Stefan Vasile Toader, Alin Gabriel Colac, Victor Vlad Costan, Elena Porumb Andrese and Daciana Elena Branisteanu

Diagnostics 2025, 15(9), 1084; https://doi.org/10.3390/diagnostics15091084 - 24 Apr 2025

Abstract

Background/Objectives: Oral lichen planus (OLP) is a chronic inflammatory mucocutaneous disorder with a recognized potential for malignant transformation. While histopathological examination remains the diagnostic gold standard, mucoscopy has emerged as a valuable non-invasive tool for assessing striae patterns, vascular features, and pigmentary [...] Read more.

Background/Objectives: Oral lichen planus (OLP) is a chronic inflammatory mucocutaneous disorder with a recognized potential for malignant transformation. While histopathological examination remains the diagnostic gold standard, mucoscopy has emerged as a valuable non-invasive tool for assessing striae patterns, vascular features, and pigmentary alterations. This study aimed to evaluate the mucoscopic characteristics of OLP across different oral mucosal sites and to compare them with other inflammatory oral conditions, assessing their diagnostic relevance. Methods: A retrospective comparative study was conducted on 106 patients, including 33 with histopathologically confirmed OLP and 73 with other inflammatory oral conditions (pemphigus vulgaris, chronic cheilitis, hyperplastic oral candidiasis, leukoplakia, squamous cell carcinoma, pachyonychia congenita, morsicatio buccarum). Mucoscopic evaluation focused on the buccal mucosa, vermilion, and lingual mucosa. Features assessed included background color, white striae patterns, vascular morphology, the presence of erosions, and other features like blunting of the lingual papillae and scales on the vermilion. Statistical analysis was carried out using SPSS 29.0. Results: Reticular striae were highly specific to OLP, particularly on the buccal mucosa (90.9%, p < 0.001). Leukoplakia-like lesions were most prevalent on the lingual mucosa and significantly associated with dotted (p = 0.027) and looped vessels (p = 0.002). Erosions correlated significantly with both dotted (p < 0.001) and linear vessels (p = 0.011), especially in lingual and vermilion lesions. In comparison, control group lesions displayed significantly more globular structures (p < 0.001), veil-like patterns (p < 0.001), and diffuse vascular distributions (p = 0.018), particularly in cheilitis and candidiasis cases. Conclusions: Mucoscopy reveals distinct site-specific patterns in OLP, supporting its role as a non-invasive diagnostic aid. Comparative analysis highlights its utility in differentiating OLP from other inflammatory oral conditions and in identifying lesions with features suggestive of malignant potential. These findings support the integration of mucoscopy into routine clinical practice and warrant further validation through larger, prospective studies. Full article

(This article belongs to the Special Issue Advances in Oral Diseases Diagnosis and Management: 2nd Edition)

28 pages, 2265 KiB

Open AccessReview

Contemporary Perspectives on Congestion in Heart Failure: Bridging Classic Signs with Evolving Diagnostic and Therapeutic Strategies

by Mihai Grigore, Camelia Nicolae, Andreea-Maria Grigore, Ana-Maria Balahura, Nicolae Păun, Gabriela Uscoiu, Ioana Verde and Adriana-Mihaela Ilieșiu

Diagnostics 2025, 15(9), 1083; https://doi.org/10.3390/diagnostics15091083 - 24 Apr 2025

Abstract

Congestion represents a defining hallmark of heart failure (HF) leading to increased morbidity and mortality in HF patients. While it was traditionally viewed as a simple and uniform state of volume overload, contemporary understanding has emphasized its complexity, distinguishing between intravascular, interstitial, and [...] Read more.

Congestion represents a defining hallmark of heart failure (HF) leading to increased morbidity and mortality in HF patients. While it was traditionally viewed as a simple and uniform state of volume overload, contemporary understanding has emphasized its complexity, distinguishing between intravascular, interstitial, and tissue congestion. Congestion contributes to overt clinical manifestation of HF. However, subclinical congestion often goes undetected, increasing the risk of adverse outcomes. Residual congestion, in particular, remains a frequent and challenging issue, with its persistence at discharge being strongly linked to rehospitalization and poor prognosis. Clinical evaluation often fails to reliably identify the resolution of congestion, highlighting the need for supplementary diagnostic methods. Improvement in imaging modalities, including lung ultrasound, venous Doppler, and echocardiography, have significantly enhanced the detection of congestion. Moreover, biomarkers such as natriuretic peptides, bioactive adrenomedullin, soluble CD146, and carbohydrate antigen 125 offer valuable, complementary insights into fluid distribution and the severity of HF congestion. Therefore, a comprehensive, multimodal strategy that integrates clinical evaluation with imaging and biomarker data is crucial for optimizing the management of congestion in HF. Future approaches should prioritize personalized decongestive therapy, addressing both intravascular and tissue congestion, while aiming to preserve renal function and limit neurohormonal activation. Refinement of these strategies holds promise for improving long-term outcomes, reducing rehospitalizations, and enhancing overall patient prognosis. Full article

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

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27 pages, 492 KiB

Open AccessSystematic Review

Mapping the Neuropsychiatric Symptoms in Alzheimer’s Disease Using Biomarkers, Cognitive Abilities, and Personality Traits: A Systematic Review

by Athanasios Chatzikostopoulos, Despina Moraitou, Vasileios Papaliagkas and Magda Tsolaki

Diagnostics 2025, 15(9), 1082; https://doi.org/10.3390/diagnostics15091082 - 24 Apr 2025

Abstract

Background/Objectives: Symptoms (NPS) in Alzheimer’s disease (AD) have multiple effects in daily living, not only for the patients but for their caregivers too. The present systematic review was performed in order to identify if biomarkers, cognitive functions, and personality traits can be considered [...] Read more.

Background/Objectives: Symptoms (NPS) in Alzheimer’s disease (AD) have multiple effects in daily living, not only for the patients but for their caregivers too. The present systematic review was performed in order to identify if biomarkers, cognitive functions, and personality traits can be considered as important factors for the development and maintenance of these symptoms. Methods: To achieve that, the existing literature spanning the period from 2018 to 2024 was critically analyzed. To be included in the review, a study had to investigate any of the factors mentioned above. In total, 182 articles were assessed for eligibility, and 50 met the inclusion criteria. Results: Most of the studies were focused on the role of biomarkers and found that amyloid β, tau and phospho-tau protein are closely related to the incidence and the severity of NPS. In fewer studies, cognitive function and personality traits were also associated with NPS. Conclusions: In conclusion, biomarkers, cognitive function and personality traits are associated with NPS, but the underlying mechanisms, still, mostly remain unknown. Full article

(This article belongs to the Special Issue Advances in the Diagnosis of Nervous System Diseases—2nd Edition)

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14 pages, 3122 KiB

Open AccessArticle

Application of ¹⁸F-FDG Positron Emission Tomography/Magnetic Resonance in Evaluation of Oropharyngeal Carcinoma

by Yilin Shen, Jichang Wu, Chenling Shen, Xinyun Huang, Cui Fan, Haixia Hu, Zenghui Cheng, Biao Li, Mingliang Xiang and Bin Ye

Diagnostics 2025, 15(9), 1081; https://doi.org/10.3390/diagnostics15091081 - 24 Apr 2025

Abstract

Objectives: Oropharyngeal carcinoma is experiencing an increase in incidence and can easily metastasize to the cervical lymph nodes. Therefore, evaluating the tumor boundary and lymph node metastasis before treatment is critical. Both CT and MR may have limitations in describing the specific boundaries [...] Read more.

Objectives: Oropharyngeal carcinoma is experiencing an increase in incidence and can easily metastasize to the cervical lymph nodes. Therefore, evaluating the tumor boundary and lymph node metastasis before treatment is critical. Both CT and MR may have limitations in describing the specific boundaries of oropharyngeal tumors. To date, no research has applied PET/MR imaging to patients with only oropharyngeal carcinoma and verified its diagnostic value. The aim of our study was to evaluate the diagnostic value of PET/MR in patients with oropharyngeal carcinoma. We prepared PET/MR for comparison with CT/MR for T and N staging, with the aim of exploring the relationship between the imaging parameters and different biological factors. Methods: This was a retrospective, observational study. In total, 13 patients (11 males and 2 females) with oropharyngeal tumors who underwent FDG PET/MR and enhanced CT/MR from July 2021 to December 2022 were retrospectively analyzed. Cohen’s kappa coefficient and the McNemar test were used to compare the consistencies and diagnostic values of FDG PET/MR and enhanced CT/MR imaging in relation to primary tumors and cervical lymph node metastases. Various specific parameters of FDG PET/MR were included in the statistics. Spearman correlation coefficients were used to analyze the relationship between the parameters and the tumor stage, the degree of differentiation, p16 expression, Ki67 expression, and serological tumor markers. Results: The average age of the patients was 61.54 ± 6.62 years old. Preoperative imaging demonstrated good consistency between FDG PET/MR and enhanced CT and MR for the diagnosis of clinical T stage. A total of seven patients underwent surgery directly. Overall, 231 cervical lymph nodes were dissected. Compared to the postoperative histopathological results, PET/MR was significantly more sensitive than enhanced CT/MR imaging (78.57% vs. 50.00%, p < 0.05; 78.57% vs. 64.29%, p < 0.05, respectively). Also, PET/MR showed more accuracy in diagnosing metastatic lymph nodes, but without significance. Combined with PET/MR-specific parameters, the SUV, TLG, and the MTV were found to be higher in the patients with more advanced stages of cancer and lower in those with p16-positive tumors. In addition, they were found to be positively correlated with the level of serum CEA. Conclusions: This is the first study to evaluate the clinical diagnostic value of PET/MR in patients with oropharyngeal carcinoma. We believe that PET/MR has more advantages in describing tumor boundaries. It is more sensitive or even more accurate for the evaluation of metastatic cervical lymph nodes. Full article

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

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