Diagnostics

14 pages, 925 KB

Open AccessArticle

Diagnostic Evaluation of an Increased Risk of Developing Small Intestinal Bacterial Overgrowth Associated with Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists and Dual GLP-1/GIP Receptor Agonists: A Global Retrospective Multicenter Cohort Analysis

by Yan Sun, Donovan Veccia, Benjamin Douglas Xun Liu, William Tse, Ronnie Fass and Gengqing Song

Diagnostics 2025, 15(17), 2264; https://doi.org/10.3390/diagnostics15172264 (registering DOI) - 7 Sep 2025

Abstract

Background/Objectives: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) effectively manage type 2 diabetes mellitus (T2DM) but may impair gastrointestinal motility, increasing the risk of small intestinal bacterial overgrowth (SIBO). Diagnostic evaluation of SIBO commonly involves breath testing and clinical assessment. This study aimed to [...] Read more.

Background/Objectives: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) effectively manage type 2 diabetes mellitus (T2DM) but may impair gastrointestinal motility, increasing the risk of small intestinal bacterial overgrowth (SIBO). Diagnostic evaluation of SIBO commonly involves breath testing and clinical assessment. This study aimed to assess the association between GLP-1 RAs or dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) RAs are associated with incident SIBO. Methods: We conducted a retrospective cohort study using the TriNetX global database, identifying adult T2DM patients initiating GLP-1 RA or dual GLP-1/GIP RA therapy versus other second-line T2DM agents (OSLT2DM) from 1 January 2006 to 2 December 2024. Patients with major abdominal surgery, connective tissue disorders, gastroparesis, or other high-risk conditions for SIBO were excluded. 1:1 Propensity score matching was applied. Short-term (<1 year) and long-term (up to 5 years) risks were evaluated with Kaplan–Meier curves and univariable Cox models. Results: After matching, 216,173 patients per cohort were analyzed. Short-term analysis demonstrated a higher incidence of diagnostically confirmed SIBO in patients treated with GLP-1 RA/GIP (0.177 per 1000 patient-years) compared to OSLT2DM (0.083 per 1000 patient-years; HR 2.14, 95% CI 1.13–4.07; p = 0.0491). Long-term analysis indicated a non-significant trend toward increased risk in the GLP-1 RA/GIP group (HR 2.02, 95% CI 0.98–4.12), though Kaplan–Meier analysis revealed a sustained divergence (p = 0.017). Conclusions: GLP-1 RA and dual GLP-1/GIP RA therapy are associated with increased short-term SIBO risk. Symptom-driven SIBO breath-test evaluation may be warranted in patients initiating these agents. Full article

(This article belongs to the Special Issue Advances in Diagnosis of Digestive Diseases)

28 pages, 16728 KB

Open AccessArticle

Deep Learning-Based DNA Methylation Detection in Cervical Cancer Using the One-Hot Character Representation Technique

by Apoorva, Vikas Handa, Shalini Batra and Vinay Arora

Diagnostics 2025, 15(17), 2263; https://doi.org/10.3390/diagnostics15172263 (registering DOI) - 7 Sep 2025

Abstract

Background: Cervical cancer is among the most prevalent malignancies in women worldwide, and early detection of epigenetic alterations such as Deoxyribose Nucleic Acid (DNA) methylation is of utmost significance for improving clinical results. This study introduces a novel deep learning-based framework for [...] Read more.

Background: Cervical cancer is among the most prevalent malignancies in women worldwide, and early detection of epigenetic alterations such as Deoxyribose Nucleic Acid (DNA) methylation is of utmost significance for improving clinical results. This study introduces a novel deep learning-based framework for predicting DNA methylation in cervical cancer, utilizing a UNet architecture integrated with an innovative one-hot character encoding technique. Methods: Two encoding strategies, monomer and dimer, were systematically evaluated for their ability to capture discriminative features from DNA sequences. Experiments were conducted on Cytosine–Guanine (CG) sites using varying sequence window sizes of 100 bp, 200 bp, and 300 bp, and sample sizes of 5000, 10,000, and 20,000. Model validation was performed on promoter regions of five cervical cancer-associated genes: miR-100, miR-138, miR-484, hTERT, and ERVH48-1. Results: The dimer encoding strategy, combined with a 300-base pair window and 5000 CG sites, emerged as the optimal configuration. The proposed framework demonstrated better predictive performance, with an accuracy of 91.60%, sensitivity of 96.71%, specificity of 87.32%, and an Area Under the Receiver Operating Characteristic (AUROC) score of 96.53, significantly outperforming benchmark deep learning models, including Convolutional Neural Networks and MobileNet. Validation on promoter regions further confirmed the robustness of the model, as it accurately identified 86.27% of methylated CG sites and maintained a strong AUROC of 83.99, demonstrating its precision–recall balance and practical relevance during validation in promoter-region genes. Conclusions: These findings establish the potential of the proposed UNet-based approach as a reliable and scalable tool for early detection of epigenetic modifications. Thus, the work contributes significantly to improving biomarker discovery and diagnostics in cervical cancer research. Full article

(This article belongs to the Special Issue Diagnosis and Management of Gynecological Cancers: Third Edition)

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20 pages, 595 KB

Open AccessReview

Liquid Biopsy’s Role in Head and Neck Tumors: Changing Paradigms in the Era of Precision Medicine

by Rudy N. Zalzal, Najla Fakhruddin and Rami Mahfouz

Diagnostics 2025, 15(17), 2262; https://doi.org/10.3390/diagnostics15172262 (registering DOI) - 7 Sep 2025

Abstract

In the era of precision medicine, liquid biopsy has become an indispensable tool in research and clinical diagnostics. This innovative molecular approach offers significant benefits in managing cancers, such as melanoma, colorectal cancer, lung cancer, and, now, head and neck tumors. By addressing [...] Read more.

In the era of precision medicine, liquid biopsy has become an indispensable tool in research and clinical diagnostics. This innovative molecular approach offers significant benefits in managing cancers, such as melanoma, colorectal cancer, lung cancer, and, now, head and neck tumors. By addressing the challenges posed by tumor heterogeneity, liquid biopsy aligns seamlessly with precision medicine strategies, providing more accessible methods to detect and monitor genetic alterations in tumors. While biomarkers for head and neck tumors have been identified, integrating these markers into diagnostic workflows remains a challenge due to the complexities of current sampling techniques. Could liquid biopsy pave the way for a breakthrough in the diagnosis, monitoring, and treatment of patients with head and neck cancer? This review explores the expanding role of liquid biopsy in oncology, with a focus on its potential to revolutionize the management of head and neck malignancies. Liquid biopsy has become an integral part of diagnosis, classification, and prognostication of numerous cancers, namely, head and neck tumors. Liquid biopsy should work in concert with histological testing, imaging, surgery, and other diagnostic and therapeutic approaches, as each offers distinct advantages that together contribute to achieving the best possible patient outcomes. Full article

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

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10 pages, 242 KB

Open AccessArticle

The “Grey Zone” in Blood Donor Screening: A Retrospective Study and Proposal for Donor Re-Entry

by Wajnat A. Tounsi, Nora Y. Hakami, Seraj O. Alamoudi, Wejdan A. Altayeb, Shahad H. Aljuhani, Afnan J. Al-Sulami, Osama A. Alzahrani, Raed M. Garout, Taghreed S. Almansouri, Waleed M. Bawazir, Aisha Qattan and Maha A. Badawi

Diagnostics 2025, 15(17), 2261; https://doi.org/10.3390/diagnostics15172261 (registering DOI) - 7 Sep 2025

Abstract

Background/Objectives: Grey zone serologic results in blood donor screening pose challenges for transfusion safety, donor management, and blood supply sustainability. In Saudi Arabia, standardized national protocols for managing grey zone outcomes remain lacking. This study aimed to evaluate the prevalence and follow-up [...] Read more.

Background/Objectives: Grey zone serologic results in blood donor screening pose challenges for transfusion safety, donor management, and blood supply sustainability. In Saudi Arabia, standardized national protocols for managing grey zone outcomes remain lacking. This study aimed to evaluate the prevalence and follow-up outcomes of grey zone serologic results among blood donors at a Saudi hospital over a five-year period. Methods: Serological screening results of six transfusion-transmissible infections (TTIs) markers were extracted alongside nucleic acid testing (NAT) results for HBV, HCV, and HIV. The grey zone was defined as a signal-to-cutoff (S/CO) of 0.90–0.99. Repeat and follow-up results, including subsequent donations, were assessed for seroconversion. Results: A total of 48,241 donations from 38,524 donors were analyzed. Anti-HBc showed the highest reactivity (n = 2312; 4.8%), followed by HbsAg (n = 2292; 0.31%) and syphilis (n = 218; 0.5%). Grey zone results were rare, and most frequent in anti-HBc (n = 76; 0.16%), HCV (n = 39; 0.08%), and HBsAg (n = 28; 0.06%). Grey zone-to-reactive conversion upon subsequent donation was rare. Three donors who initially tested in the grey zone for anti-HBc later tested reactive in subsequent donations, but their HBV NAT remained negative. Conclusions: While grey zone outcomes were infrequent, a subset involving HBV markers showed low-level reactivity on repeat testing. For other TTIs markers, grey zone results likely reflected assay variability rather than true infection. We propose a six-month temporary deferral with follow-up serologic and NAT testing, allowing conditional re-entry for donors with consistently non-reactive results, supporting both transfusion safety and a more sustainable donor pool. Full article

(This article belongs to the Section Clinical Laboratory Medicine)

12 pages, 2315 KB

Open AccessArticle

Susceptibility-Weighted Breast MRI Differentiates Abscesses from Necrotic Tumors: A Prospective Evaluation

by Fadime Güven and Muhammed Halid Yener

Diagnostics 2025, 15(17), 2260; https://doi.org/10.3390/diagnostics15172260 (registering DOI) - 7 Sep 2025

Abstract

Background/Objectives: Breast abscesses and necrotic masses often show similar peripheral enhancement and a fluid-containing appearance on breast MRI, leading to diagnostic confusion. Accurate differentiation is critical because biopsies that fail to sample the lesion wall may yield false-negative results, may be misinterpreted [...] Read more.

Background/Objectives: Breast abscesses and necrotic masses often show similar peripheral enhancement and a fluid-containing appearance on breast MRI, leading to diagnostic confusion. Accurate differentiation is critical because biopsies that fail to sample the lesion wall may yield false-negative results, may be misinterpreted as an infectious process, and delay diagnosis. Incorporating SWI into the protocol can provide additional clues to malignancy and, when warranted, prompt a second wall-targeted biopsy, thus reducing the risk of delayed cancer diagnosis. Methods: This single-center prospective diagnostic accuracy study included 42 female patients diagnosed between 2022 and 2025 with either necrotic breast tumors or abscesses, confirmed by histopathology. SWI-based Intralesional Susceptibility Score (ILSS), rim morphology, and mean ADC values were evaluated. Statistical analyses included the Mann–Whitney U test, chi-square test, ROC analysis, DeLong test for comparison of AUCs, and Cohen’s kappa for interobserver agreement. Results: SWI-based ILSS values were significantly higher in necrotic tumors compared to abscesses (mean ILSS: 2.28 vs. 0.85; 95% CI: 1.0–2.0; p < 0.001). Smooth hypointense rims were predominantly observed in abscesses (Sensitivity: 63.1%, 95% CI: 0.38–0.83; Specificity: 88.9%, 95% CI: 0.65–0.98; p = 0.001). Incomplete rim morphology was more frequent in tumors (Sensitivity: 78.9%, 95% CI: 0.54–0.93; Specificity: 77.8%, 95% CI: 0.52–0.93; p < 0.001). The double rim sign was highly specific for abscesses (Specificity: 95.2%, 95% CI: 0.76–0.99 p = 0.002). Conclusions: SWI provides valuable morphological information in differentiating abscesses from necrotic tumors on breast MRI. When used in combination with ADC values, it can enhance diagnostic accuracy. Full article

(This article belongs to the Special Issue Advances in Breast Radiology)

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20 pages, 982 KB

Open AccessArticle

Exploring IL-10 and NOS3 Genetic Variants as a Risk Factor for Neonatal Respiratory Distress Syndrome and Its Outcome

by Mădălina Anciuc-Crauciuc, George-Andrei Crauciuc, Florin Tripon, Marta Simon, Manuela Camelia Cucerea and Claudia Violeta Bănescu

Diagnostics 2025, 15(17), 2259; https://doi.org/10.3390/diagnostics15172259 (registering DOI) - 6 Sep 2025

Abstract

Background/Objective: Neonatal respiratory distress syndrome (RDS) is a leading cause of morbidity and mortality in preterm infants. Interleukin-10 (IL-10) and endothelial nitric oxide synthase (eNOS, also known as NOS3) regulate inflammation and vascular tone, and genetic variants may influence the [...] Read more.

Background/Objective: Neonatal respiratory distress syndrome (RDS) is a leading cause of morbidity and mortality in preterm infants. Interleukin-10 (IL-10) and endothelial nitric oxide synthase (eNOS, also known as NOS3) regulate inflammation and vascular tone, and genetic variants may influence the risk of RDS. To investigate the association between IL-10 rs1800872 (c.-149+1984T>G), IL-10 rs1800896 (c.-149+2474T>C), and NOS3 rs2070744 (c.-149+1691C>T), NOS3 rs1799983 (c.894T>G) variants and the risk of RDS in a Romanian cohort of preterm neonates. Methods: This case–control study included 340 preterm neonates (113 with RDS, 227 controls) born at <36 weeks of gestation. Genotyping was performed using TaqMan SNP assays. Logistic regression adjusted for gestational age and sex estimated odds ratios (ORs) and 95% confidence intervals (CIs). ROC analyses evaluated predictive performance. Results: No significant differences in genotype or allele distributions were observed between RDS and control groups for any variant. Haplotype analysis also revealed no association with RDS susceptibility or severity. NOS3:c.894T>G variant was associated with reduced risk of severe RDS after correction (adjusted p = 0.009), though survival analysis showed no significant genotype-specific effects. Epistatic genotype interaction was observed for the IL-10 T/G + T/C, present only in RDS (p = 0.0026). ROC analysis revealed a clinical prediction of RDS (AUC = 0.996), while the addition of genetic variants improved discrimination for severity (AUC = 0.865; 95% CI: 0.773–0.957) and mortality (AUC = 0.913; 95% CI: 0.791–1.000). Conclusions: IL-10 and NOS3 variants were not individually associated with overall RDS susceptibility. The observed epistatic interactions and the potential protective effect of NOS3:c.894T>G against severe forms can suggest modulatory roles in disease progression. Larger, ethnically homogeneous cohorts are needed to confirm these findings and assess their potential for informing personalized care for neonates. Full article

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

30 pages, 2016 KB

Open AccessArticle

A Novel Knowledge Fusion Ensemble for Diagnostic Differentiation of Pediatric Pneumonia and Acute Bronchitis

by Elif Dabakoğlu, Öyküm Esra Yiğit and Yaşar Topal

Diagnostics 2025, 15(17), 2258; https://doi.org/10.3390/diagnostics15172258 (registering DOI) - 6 Sep 2025

Abstract

Background: Differentiating pediatric pneumonia from acute bronchitis remains a persistent clinical challenge due to overlapping symptoms, often leading to diagnostic uncertainty and inappropriate antibiotic use. Methods: This study introduces DAPLEX, a structured ensemble learning framework designed to enhance diagnostic accuracy and reliability. A [...] Read more.

Background: Differentiating pediatric pneumonia from acute bronchitis remains a persistent clinical challenge due to overlapping symptoms, often leading to diagnostic uncertainty and inappropriate antibiotic use. Methods: This study introduces DAPLEX, a structured ensemble learning framework designed to enhance diagnostic accuracy and reliability. A retrospective cohort of 868 pediatric patients was analyzed. DAPLEX was developed in three phases: (i) deployment of diverse base learners from multiple learning paradigms; (ii) multi-criteria evaluation and pruning based on generalization stability to retain a subset of well-generalized and stable learners; and (iii) complementarity-driven knowledge fusion. In the final phase, out-of-fold predicted probabilities from the retained base learners were combined with a consensus-based feature importance profile to construct a hybrid meta-input for a Multilayer Perceptron (MLP) meta-learner. Results: DAPLEX achieved a balanced accuracy of 95.3%, an F1-score of ~0.96, and a ROC-AUC of ~0.99 on an independent holdout test. Compared to the range of performance from the weakest to the strongest base learner, DAPLEX improved balanced accuracy by 3.5–5.2%, enhanced the F1-score by 4.4–5.6%, and increased sensitivity by a substantial 8.2–13.6%. Crucially, DAPLEX’s performance remained robust and consistent across all evaluated demographic subgroups, confirming its fairness and potential for broad clinical. Conclusions: The DAPLEX framework offers a robust and transparent pipeline for diagnostic decision support. By systematically integrating diverse predictive models and synthesizing both outcome predictions and key feature insights, DAPLEX substantially reduces diagnostic uncertainty in differentiating pediatric pneumonia and acute bronchitis and demonstrates strong potential for clinical application. Full article

(This article belongs to the Special Issue Artificial Intelligence and Deep Learning in Clinical Classification and Prediction)

11 pages, 594 KB

Open AccessArticle

Nanopore 16S-Full Length and ITS Sequencing for Microbiota Identification in Intra-Abdominal Infections

by Jian-Jhou Liao, Yong-Sian Chen, Hui-Chen Lin, Yi-Ju Chen, Kuo-Lung Lai, Yan-Chiao Mao, Po-Yu Liu and Han-Ni Chuang

Diagnostics 2025, 15(17), 2257; https://doi.org/10.3390/diagnostics15172257 (registering DOI) - 6 Sep 2025

Abstract

Background/Objectives: Intra-abdominal infections (IAIs) constitute significant clinical challenges that can rapidly progress to life-threatening conditions if not promptly diagnosed and treated. Traditional pathogen identification methodologies, predominantly culture-based, frequently necessitate extended turnaround times (TATs) and exhibit limitations in detecting polymicrobial or anaerobic infections. [...] Read more.

Background/Objectives: Intra-abdominal infections (IAIs) constitute significant clinical challenges that can rapidly progress to life-threatening conditions if not promptly diagnosed and treated. Traditional pathogen identification methodologies, predominantly culture-based, frequently necessitate extended turnaround times (TATs) and exhibit limitations in detecting polymicrobial or anaerobic infections. Methods: We implemented Oxford Nanopore Technology (ONT) sequencing to analyze the microbiota in patients with IAIs at Taichung Veterans General Hospital. The study cohort comprised sixteen patients with IAIs. Following specimen collection, DNA extraction was performed, and then full-length 16S rRNA and ITS region amplification and subsequent ONT sequencing were conducted. Results: Conventional clinical culture-based methodologies detected pathogens in 13 patients. Among the 14 successfully sequenced specimens, ONT sequencing elucidated a diverse spectrum of bacteria and fungi, with read counts ranging from 375 to 19,716. Polymicrobial and anaerobe-enriched communities were predominantly observed in lower gastrointestinal tract infections, specifically colonic or small bowel perforations, whereas upper gastrointestinal perforations, including those of the stomach or duodenum, were frequently dominated by Streptococcus, Granulicatella, or Candida species. The sequencing identified pathogens concordant with culture results, including Escherichia coli, Enterococcus, and Candida albicans. In addition, anaerobic or low-abundance taxa were exclusively identifiable through sequencing methodologies. Conclusions: ONT sequencing facilitated results within up to 24 h and successfully detected pathogens in culture-negative cases. These findings underscore the utility of ONT sequencing as an expeditious and comprehensive diagnostic modality for IAIs. Full article

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

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9 pages, 854 KB

Open AccessBrief Report

The Effects of Age on the Human Tear Film Assessed with a Novel Imaging Device

by Alice Verticchio Vercellin, Lauren J. Isserow, Richard B. Rosen, Paul A. Sidoti, Brent A. Siesky, Keren Wood, Nathan Schanzer, Francesco Oddone, Carmela Carnevale, Tak Yee Tania Tai, Masako Chen, Kira Manusis, Katy Tai, David J. Brenner, Norman J. Kleiman, Samuel Potash, George J. Eckert and Gal Antman

Diagnostics 2025, 15(17), 2256; https://doi.org/10.3390/diagnostics15172256 (registering DOI) - 6 Sep 2025

Abstract

Purpose: We aimed to analyze the effects of age on human tear film (TF) using a novel nanometer resolution TF imaging device (Tear Film Imager, TFI, AdOM, Israel). Methods: 44 healthy adult subjects (≥18 years of age) without ocular or systemic diseases or [...] Read more.

Purpose: We aimed to analyze the effects of age on human tear film (TF) using a novel nanometer resolution TF imaging device (Tear Film Imager, TFI, AdOM, Israel). Methods: 44 healthy adult subjects (≥18 years of age) without ocular or systemic diseases or prior eye treatments with ages spanning seven decades were enrolled in this prospective cross-sectional study. Subjects underwent a comprehensive ophthalmic examination and completed the Ocular Surface Disease Index questionnaire (OSDI). All study participants underwent TF imaging using the TFI, including assessment of muco-aqueous layer thickness (MALT), lipid-layer thickness (LLT), inter-blink interval, and lipid map uniformity. Associations between TFI parameters and age were tested using linear regression (accounting for multiple eyes). Results: A total of 80 eyes (44 subjects) were imaged: 19 eyes from 10 subjects in the 3rd decade of life (aged 20–29); 10 eyes from 5 subjects in the 4th decade of life (aged 30–39); 5 eyes from 3 subjects in the 5th decade of life (40–49); 12 eyes from 7 subjects in the 6th decade of life (50–59), 19 eyes from 11 subjects in the 7th decade of life (60–69); 11 eyes from 6 subjects in the 8th decade of life (70–79); and 4 eyes from 2 subjects in the 9th decade of life (80–89). With increasing age, MALT significantly decreased (p = 0.024), and LLT significantly increased (p = 0.001). No statistically significant linear age effects were found for the other TFI parameters (p > 0.05) or the OSDI scores of study participants of different ages (p = 0.786). Conclusions: Quantitative TF biomarkers varied significantly with advancing age in healthy individuals, highlighting the importance of accounting for age in TF assessments. Full article

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

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11 pages, 949 KB

Open AccessArticle

Patient-Reported Outcomes of Microfracture, Nanofracture, and K-Wire Drilling in Talus Osteochondral Lesions

by Ahmet Görkem Kasapoğlu, Mehmet Arıcan, Yıldıray Tekçe, Giray Tekçe and İlyas Kaban

Diagnostics 2025, 15(17), 2255; https://doi.org/10.3390/diagnostics15172255 (registering DOI) - 6 Sep 2025

Abstract

Background/Objectives: Different patient-reported outcomes and radiological results are reported depending on whether microfracture, drilling, or nanofracture is utilized in the arthroscopic treatment of talus osteochondral lesions, but the first-line treatment is still controversial. The aim of this study is to evaluate the early [...] Read more.

Background/Objectives: Different patient-reported outcomes and radiological results are reported depending on whether microfracture, drilling, or nanofracture is utilized in the arthroscopic treatment of talus osteochondral lesions, but the first-line treatment is still controversial. The aim of this study is to evaluate the early patient-reported outcomes of microfracture, nanofracture, and antegrade drilling methods in talus anteromedial osteochondral lesions. Methods: A total of 77 patients who presented with ankle pain between October 2016 and June 2022, were diagnosed with talus osteochondral lesions, and underwent microfracture (n: 27), nanofracture (n: 25), and K-wire drilling (n: 25) were included. Demographic data of the patients were evaluated, such as age, gender, lesion side, dominant extremity, body mass index (BMI), smoking status, smoking (pack/day-year), and symptom duration. Patient-reported outcomes of the patients were evaluated with VAS (visual analog scale) and AOFAS (American Orthopedic Foot & Ankle Society) scores measured before surgery and at 6 and 12 months after surgery. The results were evaluated at the significance level of p < 0.05. Results: There were no statistically significant differences among the microfracture, nanofracture, and drilling groups in terms of age, gender, lesion side, dominant extremity, BMI, smoking, or daily cigarette use (p = 0.121, p = 0.852, p = 0.956, p = 0.731, p = 0.881, p = 0.769, p = 0.124). Similarly, the mean duration of symptoms did not differ significantly between the groups (p = 0.336). Although AOFAS and VAS scores significantly improved in all groups (p = 0.0001), there were no statistically significant differences between the microfracture, nanofracture, and drilling groups at preoperative, 6th-, and 12th-month measuring points. The microfracture group showed a significantly higher AOFAS improvement from preop to 6 months compared to the other groups (p = 0.012), though no differences were found between nanofracture and drilling or in 12-month changes. VAS percentage changes showed no significant differences among groups at either time point. Conclusions: All treatment groups had similar baseline characteristics and outcomes, with the microfracture group showing a greater functional improvement at 6 months. Full article

(This article belongs to the Special Issue Recent Advances in Bone and Joint Imaging—3rd Edition)

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4 pages, 659 KB

Open AccessInteresting Images

A Patient Presenting with Joint Deformities and ST-Elevation Myocardial Infarction

by Emil J. Dąbrowski, Wiktoria U. Kozłowska, Patrycja O. Lipska, Marcin Kożuch and Sławomir Dobrzycki

Diagnostics 2025, 15(17), 2254; https://doi.org/10.3390/diagnostics15172254 (registering DOI) - 5 Sep 2025

Abstract

A 62-year-old man presented with ST-elevation myocardial infarction and advanced tophaceous gout, despite long-term urate-lowering therapy. His history included chronic kidney disease, hypertension, heart failure, and atrial fibrillation. Examination revealed severe joint deformities with multiple tophi. Coronary angiography showed multivessel disease with critical [...] Read more.

A 62-year-old man presented with ST-elevation myocardial infarction and advanced tophaceous gout, despite long-term urate-lowering therapy. His history included chronic kidney disease, hypertension, heart failure, and atrial fibrillation. Examination revealed severe joint deformities with multiple tophi. Coronary angiography showed multivessel disease with critical right coronary artery stenosis, treated with primary percutaneous coronary intervention. Following a Heart Team consultation, the patient was bridged with cangrelor and underwent urgent hybrid coronary artery bypass grafting and left atrial appendage occlusion. This case highlights the systemic burden of treatment-refractory gout, with progressive cardiovascular and renal complications. Tophaceous gout represents a distinct, high-risk phenotype associated with increased mortality and reduced quality of life. Despite standard therapies, this patient experienced continued disease progression, prompting referral for advanced treatment with pegloticase and canakinumab. Multidisciplinary care and personalized strategies are essential in managing severe, refractory gout with multi-organ involvement. Full article

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

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18 pages, 3709 KB

Open AccessArticle

AI-Based Response Classification After Anti-VEGF Loading in Neovascular Age-Related Macular Degeneration

by Murat Fırat, İlknur Tuncer Fırat, Ziynet Fadıllıoğlu Üstündağ, Emrah Öztürk and Taner Tuncer

Diagnostics 2025, 15(17), 2253; https://doi.org/10.3390/diagnostics15172253 - 5 Sep 2025

Abstract

Background/Objectives: Wet age-related macular degeneration (AMD) is a progressive retinal disease characterized by macular neovascularization (MNV). Currently, the standard treatment for wet AMD is intravitreal anti-VEGF administration, which aims to control disease activity by suppressing neovascularization. In clinical practice, the decision to [...] Read more.

Background/Objectives: Wet age-related macular degeneration (AMD) is a progressive retinal disease characterized by macular neovascularization (MNV). Currently, the standard treatment for wet AMD is intravitreal anti-VEGF administration, which aims to control disease activity by suppressing neovascularization. In clinical practice, the decision to continue or discontinue treatment is largely based on the presence of fluid on optical coherence tomography (OCT) and changes in visual acuity. However, discrepancies between anatomic and functional responses can occur during these assessments. Methods: This article presents an artificial intelligence (AI)-based classification model developed to objectively assess the response to anti-VEGF treatment in patients with AMD at 3 months. This retrospective study included 120 patients (144 eyes) who received intravitreal bevacizumab treatment. After bevacizumab loading treatment, the presence of subretinal/intraretinal fluid (SRF/IRF) on OCT images and changes in visual acuity (logMAR) were evaluated. Patients were divided into three groups: Class 0, active disease (persistent SRF/IRF); Class 1, good response (no SRF/IRF and ≥0.1 logMAR improvement); and Class 2, limited response (no SRF/IRF but with <0.1 logMAR improvement). Pre-treatment and 3-month post-treatment OCT image pairs were used for training and testing the artificial intelligence model. Based on this grouping, classification was performed with a Siamese neural network (ResNet-18-based) model. Results: The model achieved 95.4% accuracy. The macro precision, macro recall, and macro F1 scores for the classes were 0.948, 0.949, and 0.948, respectively. Layer Class Activation Map (LayerCAM) heat maps and Shapley Additive Explanations (SHAP) overlays confirmed that the model focused on pathology-related regions. Conclusions: In conclusion, the model classifies post-loading response by predicting both anatomic disease activity and visual prognosis from OCT images. Full article

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

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15 pages, 749 KB

Open AccessArticle

The Predictive Value of Clinical Signs to Identify Shock in Critically Ill Patients

by Matthias Noitz, Sabine Preining, Dominik Jenny, Simon Langthaler, Romana Erblich, Thomas Tschoellitsch, Jens Meier and Martin W. Dünser

Diagnostics 2025, 15(17), 2252; https://doi.org/10.3390/diagnostics15172252 - 5 Sep 2025

Abstract

Background/Objectives: Current guidelines recommend the use of clinical signs to diagnose shock and cellular hypoperfusion in critically ill patients. However, these recommendations are based on limited scientific evidence. The objective was to determine the predictive value of clinical signs to identify shock. Methods: [...] Read more.

Background/Objectives: Current guidelines recommend the use of clinical signs to diagnose shock and cellular hypoperfusion in critically ill patients. However, these recommendations are based on limited scientific evidence. The objective was to determine the predictive value of clinical signs to identify shock. Methods: Retrospective cohort study including adult (≥18 years) patients admitted to the critical care resuscitation unit of a tertiary hospital. The primary goal was to determine the predictive value of tachycardia, prolonged capillary refill time (CRT), skin mottling, weak radial pulse, inadequate peripheral perfusion, shock index >0.8, altered mental state, and diaphoresis to identify shock. Two-by-two contingency tables were used for statistical analysis. Results: Three-hundred-seventeen patients (no shock, n = 231; shock, n = 86) were included. As a single clinical sign, skin mottling [sensitivity, 0.38; specificity, 0.92; negative likelihood ratio (LR−), 0.68; positive likelihood ratio (LR+), 4.62], prolonged CRT (sensitivity, 0.44; specificity, 0.89; LR−, 0.62; LR+, 4.17), shock index >0.8 [sensitivity, 0.77; specificity, 0.64; LR−, 0.36; LR+, 2.15], a weak radial pulse [sensitivity, 0.62; specificity, 0.79; LR−, 0.49; LR+, 2.88], and inadequate peripheral perfusion [sensitivity, 0.68; specificity, 0.73; LR−, 0.44; LR+, 2.52] predicted shock. Prolonged CRT, skin mottling, inadequate peripheral perfusion, a weak radial pulse, and a shock index >0.8 predicted shock states with low cardiac output. A shock index >0.8, tachycardia, and a weak radial pulse were predictive of distributive/vasodilatory shock. The accuracy to identify shock were higher if ≥2 clinical signs were present compared to only one. Conclusions: Skin mottling, prolonged CRT, shock index >0.8, weak radial pulse, and inadequate peripheral perfusion can identify patients with shock, particularly shock states with low cardiac output, with high specificity and LR+. Full article

(This article belongs to the Special Issue Diagnostics in the Emergency and Critical Care Medicine)

14 pages, 673 KB

Open AccessArticle

Fetal and Neonatal Outcomes in Fetuses with an Estimated Fetal Weight Percentile of 10–20 in the Early Third Trimester: A Retrospective Cohort Study

by Miguel A. Mendez-Piña, Mario I. Lumbreras-Marquez, Sandra Acevedo-Gallegos, Berenice Velazquez-Torres, Maria J. Rodriguez-Sibaja, Dulce M. Camarena-Cabrera and Juan M. Gallardo-Gaona

Diagnostics 2025, 15(17), 2251; https://doi.org/10.3390/diagnostics15172251 - 5 Sep 2025

Abstract

Background: Fetal size is often dichotomized as normal or abnormal using the 10th percentile of estimated fetal weight (EFW) or abdominal circumference as a cutoff. While the risk of adverse perinatal outcomes decreases with increasing fetal weight percentile, no percentile completely eliminates that [...] Read more.

Background: Fetal size is often dichotomized as normal or abnormal using the 10th percentile of estimated fetal weight (EFW) or abdominal circumference as a cutoff. While the risk of adverse perinatal outcomes decreases with increasing fetal weight percentile, no percentile completely eliminates that risk. Objective: The aim of this study was to compare perinatal outcomes between fetuses with an EFW between the 10th and 20th percentiles and those with an EFW between the 20th and 90th percentiles (i.e., >20 and <90) at the beginning of the accelerated growth stage (28.0–30.0 weeks’ gestation). Methods: We conducted a retrospective cohort study of singleton pregnancies managed at a quaternary center in Mexico City (2017–2024). Outcomes were compared based on EFW percentiles at 28.0–30.0 weeks. The primary outcome was adverse neonatal outcome (ANeO), defined as the presence of at least one of the following: umbilical artery pH ≤ 7.1, 5 min Apgar ≤ 7, NICU admission, early neonatal hypoglycemia, non-reassuring fetal status, respiratory distress syndrome, intraventricular hemorrhage, hypoxic–ischemic encephalopathy, or perinatal death. Secondary outcomes included progression to fetal growth restriction (FGR) and low birth weight. Modified Poisson regression was used to estimate adjusted risk ratios (aRRs) with 95% confidence intervals (CIs). Results: Among 650 cases, ANeO occurred in 45.8% of fetuses in the 10th–20th percentile group vs. 29.4% in the 20th–90th percentile group (aRR: 1.51, 95% CI: 1.22–1.86; p < 0.001). FGR and low birth weight were also more frequent in the 10th–20th percentile group (21.1% and 27.6% vs. 6.4% and 5.8%, respectively; p < 0.001). Conclusions: Fetuses between the 10th and 20th percentiles at 28–30 weeks have increased risks of neonatal morbidity, FGR, and low birth weight. Full article

(This article belongs to the Special Issue Diagnosis and Management of Contemporary Issues in Maternal-Fetal Medicine)

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16 pages, 3521 KB

Open AccessArticle

Temporal Trends and Machine Learning-Based Risk Prediction of Female Infertility: A Cross-Cohort Analysis Using NHANES Data (2015–2023)

by Ismat Ara Begum, Deepak Ghimire and A. S. M. Sanwar Hosen

Diagnostics 2025, 15(17), 2250; https://doi.org/10.3390/diagnostics15172250 - 5 Sep 2025

Abstract

Background: Female infertility represents a significant global public health concern, yet its evolving trends and data-driven risk prediction remain under examined in nationally representative cohorts. This study investigates temporal changes in infertility prevalence and evaluates Machine Learning (ML) models for infertility risk prediction [...] Read more.

Background: Female infertility represents a significant global public health concern, yet its evolving trends and data-driven risk prediction remain under examined in nationally representative cohorts. This study investigates temporal changes in infertility prevalence and evaluates Machine Learning (ML) models for infertility risk prediction using harmonized clinical features from NHANES cycles (2015, 2016, 2017, 2018, 2021, 2022, and 2023). Methods: Women aged 19 to 45 with complete data on infertility-related variables (including reproductive history, menstrual irregularity, Pelvic Infection Disease (PID), hysterectomy, and bilateral oophorectomy) were analyzed. Descriptive statistics and cohort comparisons employed ANOVA and Chi-square tests, while multivariate Logistic Regression (LR) estimated Adjusted Odds Ratios (OR) and informed feature importance. Predictive models (LR, Random Forest, XGBoost, Naive Bayes, SVM, and a Stacking Classifier ensemble) were trained and tuned via GridSearchCV with five-fold cross-validation. Model performance was evaluated using accuracy, precision, recall, F1-score, specificity, and AUC-ROC. Results: We observed a notable increase in infertility prevalence from 14.8% in 2017–2018 to 27.8% in 2021–2023, suggesting potential post-pandemic impacts on reproductive health. In multivariate analysis, prior childbirth emerged as the strongest protective factor (Adjusted OR

\approx 0.00

), while menstrual irregularity showed a significant positive association with infertility (OR

= 0.55

, 95% CI

0.40

to

0.77

,

p < 0.001

). Unexpectedly, PID, hysterectomy, and bilateral oophorectomy were not significantly associated with infertility after adjustment (

p > 0.05

), which may partly reflect the inherent definition of self-reported infertility used in this study. All six ML models demonstrated excellent and comparable predictive ability (AUC

> 0.96

), reinforcing the effectiveness of even a minimal common predictor set for infertility risk stratification. Conclusions: The rising prevalence of self-reported infertility among U.S. women underscores emerging public health challenges. Despite relying on a streamlined feature set, interpretable and ensemble ML models successfully predicted infertility risk, showcasing their potential applicability in broader surveillance and personalized care strategies. Future models should integrate additional sociodemographic and behavioral factors to enhance precision and support tailored interventions. Full article

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

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26 pages, 2924 KB

Open AccessArticle

Simultaneous Detection and Differentiation of SARS-CoV-2, Influenza A/B, and Respiratory Syncytial Viruses in Respiratory Specimens Using the VitaSIRO solo™ SARS-CoV-2/Flu/RSV Assay

by Ralph-Sydney Mboumba Bouassa, Sarah Lukumbisa and Laurent Bélec

Diagnostics 2025, 15(17), 2249; https://doi.org/10.3390/diagnostics15172249 - 5 Sep 2025

Abstract

Background/Objectives: The concurrent circulation of SARS-CoV-2 with influenza A and B viruses and respiratory syncytial virus (RSV) represents a new diagnostic challenge in the post-COVID-19 area, especially considering that these infections have overlapping clinical presentations but different approaches to treatment and management. Multiplexed [...] Read more.

Background/Objectives: The concurrent circulation of SARS-CoV-2 with influenza A and B viruses and respiratory syncytial virus (RSV) represents a new diagnostic challenge in the post-COVID-19 area, especially considering that these infections have overlapping clinical presentations but different approaches to treatment and management. Multiplexed molecular testing on point-of-care platforms that focus on the simultaneous detection of multiple respiratory viruses in a single tube constitutes a useful approach for diagnosis of respiratory infections in decentralized clinical settings. This study evaluated the analytical performances of the VitaSIRO solo™ SARS-CoV-2/Flu/RSV Assay performed on the VitaSIRO solo™ Instrument (Credo Diagnostics Biomedical Pte. Ltd., Singapore, Republic of Singapore). Methods: With a view to accreditation, the criteria of the 2022-revised EN ISO 15189:2022 norma were applied for the retrospective on-site verification of method using anonymized respiratory specimens collected during the last 2024–2025 autumn–winter season in France. Results: Usability and satisfaction were comparable to current reference point-of-care platforms, such as the Cepheid GeneXpert^® Xpress System (Cepheid Diagnostics, Sunnyvale, CA, USA). Repeatability and reproducibility (2.34–4.49% and 2.78–5.71%, respectively) demonstrated a high level of precision. The platform exhibited a low invalid rate (2.9%), with most resolving on retesting. Analytical performance on 301 clinical samples showed high overall sensitivities: 94.8% for SARS-CoV-2 (Ct ≤ 33), 95.8% for influenza A and B viruses, 95.2% for RSV, and 95.4% for all viruses. Specificities were consistently high (99.2–100.0%). False negatives (2.6%) were predominantly associated with high Ct values. Agreement with the comparator reference NeuMoDx™ Flu A-B/RSV/SARS-CoV-2 Vantage Assay (Qiagen GmbH, Hilden, Germany) was almost perfect (Cohen’s κ 0.939–0.974), and a total of 91.1%, 94.8%, and 100.0% of Ct values were within the 95% limits of agreement for the detection of SARS-CoV-2, influenza A and B viruses, and RSV, respectively, by Bland–Altman analyses. Passing–Bablok regression analyses demonstrated good Ct values correlation between VitaSIRO solo™ and NeuMoDx™ assays, with a slight, non-significant, positive bias for the VitaSIRO solo™ assay (mean absolute bias +0.509 to +0.898). Conclusions: These findings support VitaSIRO solo™ Instrument as a user-friendly and reliable point-of-care platform for the rapid detection and differentiation of SARS-CoV-2, influenza A and B viruses, and RSV responding to the EN ISO 15189:2022 criteria for accreditation to be implemented in hospital or decentralized settings. Full article

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

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18 pages, 2228 KB

Open AccessArticle

Artificial Intelligence-Based MRI Segmentation for the Differential Diagnosis of Single Brain Metastasis and Glioblastoma

by Daniela Pomohaci, Emilia-Adriana Marciuc, Bogdan-Ionuț Dobrovăț, Mihaela-Roxana Popescu, Ana-Cristina Istrate, Oriana-Maria Onicescu (Oniciuc), Sabina-Ioana Chirica, Costin Chirica and Danisia Haba

Diagnostics 2025, 15(17), 2248; https://doi.org/10.3390/diagnostics15172248 - 5 Sep 2025

Abstract

Background/Objectives: Glioblastomas (GBMs) and brain metastases (BMs) are both frequent brain lesions. Distinguishing between them is crucial for suitable therapeutic and follow-up decisions, but this distinction is difficult to achieve, as it includes clinical, radiological and histopathological correlation. However, non-invasive AI examination [...] Read more.

Background/Objectives: Glioblastomas (GBMs) and brain metastases (BMs) are both frequent brain lesions. Distinguishing between them is crucial for suitable therapeutic and follow-up decisions, but this distinction is difficult to achieve, as it includes clinical, radiological and histopathological correlation. However, non-invasive AI examination of conventional and advanced MRI techniques can overcome this issue. Methods: We retrospectively selected 78 patients with confirmed GBM (39) and single BM (39), with conventional MRI investigations, consisting of T2W FLAIR and CE T1W acquisitions. The MRI images (DICOM) were evaluated by an AI segmentation tool, comparatively evaluating tumor heterogeneity and peripheral edema. Results: We found that GBMs are less edematous than BMs (p = 0.04) but have more internal necrosis (p = 0.002). Of the BM primary cancer molecular subtypes, NSCCL showed the highest grade of edema (p = 0.01). Compared with the ellipsoidal method of volume calculation, the AI machine obtained greater values when measuring lesions of the occipital and temporal lobes (p = 0.01). Conclusions: Although extremely useful in radiomics analysis, automated segmentation applied alone could effectively differentiate GBM and BM on a conventional MRI, calculating the ratio between their variable components (solid, necrotic and peripheral edema). Other studies applied to a broader set of participants are necessary to further evaluate the efficacy of automated segmentation. Full article

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

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11 pages, 650 KB

Open AccessArticle

Stratifying Treatment-Resistant Monosymptomatic Nocturnal Enuresis: Identifying the Subgroup Most Responsive to Biofeedback Therapy

by Emre Kandemir, Ali Sezer and Mehmet Sarikaya

Diagnostics 2025, 15(17), 2247; https://doi.org/10.3390/diagnostics15172247 - 5 Sep 2025

Abstract

Background/Objectives: A subset of children with monosymptomatic nocturnal enuresis (MNE) remains unresponsive to standard treatments such as desmopressin and alarm therapy. This study aimed to identify clinical predictors of response to biofeedback therapy in treatment-resistant MNE and to evaluate the role of [...] Read more.

Background/Objectives: A subset of children with monosymptomatic nocturnal enuresis (MNE) remains unresponsive to standard treatments such as desmopressin and alarm therapy. This study aimed to identify clinical predictors of response to biofeedback therapy in treatment-resistant MNE and to evaluate the role of bladder capacity as a stratification parameter. Methods: In this prospective study, 89 children with treatment-resistant MNE underwent six weekly sessions of biofeedback therapy involving visual pelvic floor feedback. Based on treatment outcomes, patients were classified as complete responders or partial/non-responders. Clinical characteristics including age-adjusted maximal voided volume (MVV), nocturnal polyuria, and wetting frequency were compared. Results: Patients with a complete response had significantly lower baseline MVV and age-adjusted MVV (p < 0.001). Nocturnal overactivity was more common among responders (60.6% vs. 33.9%, p = 0.017), whereas nocturnal polyuria was more frequent in non-responders (p = 0.027). Age-adjusted MVV emerged as the only independent predictor of treatment success in multivariate analysis (p = 0.045), with ROC analysis confirming its predictive value (AUC = 0.767, 95% CI: 0.667–0.866). Conclusions: These findings suggest that reduced bladder capacity and frequent night-time wetting may help identify patients who are more likely to benefit from biofeedback therapy. Bladder capacity assessment may thus serve as a useful tool in tailoring management strategies for refractory MNE. Full article

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

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24 pages, 1636 KB

Open AccessReview

Diagnostic Innovations to Combat Antibiotic Resistance in Critical Care: Tools for Targeted Therapy and Stewardship

by Ahmed D. Alatawi, Helal F. Hetta, Mostafa A. Sayed Ali, Yasmin N. Ramadan, Amirah B. Alaqyli, Wareef K. Alansari, Nada H. Aldhaheri, Talidah A. Bin Selim, Shahad A. Merdad, Maram O. Alharbi, Wejdan Alhumaidi Hmdan Alatawi and Abdelazeem M. Algammal

Diagnostics 2025, 15(17), 2244; https://doi.org/10.3390/diagnostics15172244 - 5 Sep 2025

Abstract

Antibiotic resistance is a growing global health threat, with critical care settings representing one of the most vulnerable arenas due to the high burden of infection and frequent empirical antibiotic use. Rapid and precise diagnosis of infectious pathogens is crucial for initiating appropriate [...] Read more.

Antibiotic resistance is a growing global health threat, with critical care settings representing one of the most vulnerable arenas due to the high burden of infection and frequent empirical antibiotic use. Rapid and precise diagnosis of infectious pathogens is crucial for initiating appropriate therapy, minimizing unnecessary antimicrobial exposure, and supporting effective stewardship programs. This review explores how innovative diagnostic technologies are reshaping infection management and antimicrobial stewardship in critical care. We examine the clinical utility of molecular assays, multiplex PCR, MALDI-TOF mass spectrometry, metagenomic sequencing, point-of-care (POC) diagnostics, and emerging tools like biosensors and AI-powered predictive models. These platforms enable earlier pathogen identification and resistance profiling, facilitating timely and targeted therapy while minimizing unnecessary broad-spectrum antibiotic use. By integrating diagnostics into stewardship frameworks, clinicians can optimize antimicrobial regimens, improve patient outcomes, and reduce resistance selection pressure. Despite their promise, adoption is challenged by cost, infrastructure, interpretation complexity, and inequitable access, particularly in low-resource settings. Future perspectives emphasize the need for scalable, AI-enhanced, and globally accessible diagnostic solutions. In bridging innovation with clinical application, diagnostic advancements can serve as pivotal tools in the global effort to curb antimicrobial resistance in critical care environments. Full article

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

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