Diagnostics doi: 10.3390/diagnostics16101485

Authors: Marwa Chendeb El Rai Aicha Beya Far Muna Darweesh Salam Dhou Nour Aburaed Salah El Rai Mohammed ElKhazendar Samer Ellahham

Radiology services are experiencing increasing operational complexity due to rising imaging volumes and expanding coordination demands across interconnected clinical and administrative processes. This complexity is reflected in variability across workflow stages, driven by fragmented information flows, heterogeneous system integration, and multi-source data dependencies. Artificial intelligence (AI) has therefore emerged as a potential tool to support automation, prioritization, and operational efficiency throughout the radiology pathway. This narrative review examines published applications of AI within a nine-stage representation of the radiology workflow. The review synthesizes how AI methods are being investigated to support both administrative coordination and diagnostic processes in radiology practice. AI approaches aim to reduce repetitive administrative tasks, improve resource utilization, and assist radiologists in managing increasing imaging workloads. However, research activity remains uneven, with a strong concentration on later-stage tasks such as image analysis and reporting, while earlier and administrative stages remain comparatively underexplored. By organizing existing research within a unified workflow-oriented framework, this review highlights areas of concentration and identifies gaps across less-studied stages. The findings suggest that while several AI applications are approaching early clinical deployment, broader workflow-level impact remains limited by challenges related to system integration, interoperability, governance, and real world implementation. Continued progress will depend on developing integrated and clinically validated solutions that extend beyond isolated tasks to support coordinated radiology workflow optimization.

Diagnostics doi: 10.3390/diagnostics16101483

Authors: Hidetoshi Satomi Ayumi Ryu Azusa Shingetsu Satoshi Tanada Keiichiro Honma

Background/Objectives: Trichoblastoma is a benign follicular adnexal tumor that typically arises on the head and neck. Large variants at atypical locations pose considerable diagnostic challenges because their clinical presentation can be indistinguishable from malignant soft tissue neoplasms. Herein, we describe a case of trichoblastoma presenting as a large subcutaneous thigh mass that was correctly diagnosed by fine-needle aspiration cytology. Case Presentation: A 49-year-old male presented with a 7 cm, slowly enlarging, subcutaneous mass in the left thigh of 20 years’ duration. Magnetic resonance imaging raised the possibility of a low-grade sarcoma. Fine-needle aspiration cytology yielded cohesive clusters of basaloid cells with peripheral palisading, delicate spindle-shaped follicular stromal cells intimately admixed with the epithelial component, and orangeophilic keratinous material in the background. The absence of nuclear atypia, mitotic figures, and mucinous stroma supported a preoperative cytological diagnosis of a benign follicular germinative tumor consistent with trichoblastoma, thereby guiding conservative surgical excision. Histopathological examination confirmed the diagnosis. Immunohistochemistry revealed focally positive BerEP4, CD34-positive stroma, negative androgen receptor, and positive bcl-2, consistent with trichoblastoma and distinguishing the tumor from basal cell carcinoma. The patient remained recurrence-free 12 months after surgery. Conclusions: Careful assessment of characteristic cytomorphological features, particularly a dual population of basaloid epithelial cells with peripheral palisading and specialized follicular stromal cells, is vital for the accurate preoperative cytological characterization of trichoblastoma, even at atypical anatomical sites.

Diagnostics doi: 10.3390/diagnostics16101482

Authors: Alice Verticchio Vercellin Samuel Potash Kira Manusis Paul A. Sidoti Richard B. Rosen Brent A. Siesky Keren Wood Lily A. Greenberg Peter D'Amelia Edan Kenig Norman J. Kleiman David J. Brenner George J. Eckert Lucia Tanga Carmela Carnevale Masako Chen David Qi Minwoo Kwon Gal Antman

Background/Objectives: The aim of this study was to investigate the effects of intraocular pressure (IOP)-lowering drops on the sublayers of the human tear film as assessed by a novel nanometer-resolution Tear Film Imager (TFI, AdOM, Israel). Methods: In a prospective, cross-sectional study, 98 eyes from 56 adult human subjects were imaged using the TFI. The dataset included data from 18 eyes from 12 subjects treated with preserved IOP-lowering drops and 80 eyes from 44 control subjects not under ocular hypotensive therapy. Subjects in the IOP treatment group used a variety of IOP-lowering medications, including prostaglandin analogs, beta-blockers, carbonic anhydrase inhibitors, alpha agonists, and combination drops. A linear mixed effects model was used to assess the association between IOP-lowering therapy and tear film (TF) metrics, controlling for age and intra-individual correlation. The following parameters were measured: muco-aqueous layer thickness (MALT), muco-aqueous layer thinning rate (MALTR), lipid layer thickness (LLT), lipid map uniformity (LMU), inter-blink intervals (IBI), and lipid break-up time (LBUT). Results: Average ages significantly differed (p = 0.013) between the treatment group (66.5 years) and control group (average age 51.5 years), and thus results were adjusted for age accordingly. IOP was 17.1 mmHg in the treatment group and 16.1 mmHg in the control group. When analyzing the sublayers of the TF, MALTR had a significant association with IOP-lowering therapy after adjusting for age, with a difference of −52.68 nm/s; 95% confidence interval [−96.87, −8.48]; p-value = 0.020. Additionally, IBI was significantly associated with IOP-lowering therapy after log transformation (p = 0.049), with shorter IBI in the treatment group. All other metrics (MALT, LLT, LMU, and LBUT) were statistically insignificant (p > 0.05). Conclusions: These pilot results suggest that IOP-lowering drops may accelerate thinning of the TF, specifically the muco-aqueous layer. Longitudinal studies with significantly larger samples are needed to specify the differential impact of various ocular hypotensive therapies on the human TF and the clinical implications of these findings.

Diagnostics doi: 10.3390/diagnostics16101481

Authors: David Luengo Gómez Ángel Francisco Ávila Jiménez Miguel Ángel Araújo-Jiménez Encarnación González Flores Consolación Melguizo Alonso Mercedes Zurita Herrera Antonio Jesús Láinez Ramos-Bossini Ángela Salmerón Ruiz

Introduction: Magnetic resonance imaging (MRI) is the reference imaging modality for locoregional staging and restaging of rectal cancer (RC). However, its agreement with surgical pathology in real-world practice is limited. We aimed to assess the agreement and diagnostic performance of preoperative MRI for dichotomized T and N staging in RC. Secondarily, we explored the direction of MRI misclassification and potential preoperative factors associated with discordance. Methods: We conducted a retrospective real-world study on 152 consecutive patients with pathologically confirmed RC who underwent surgery between September 2019 and June 2025 in our institution. Two cohorts were analyzed separately: patients treated without neoadjuvant therapy (non-NAT, n = 70) and patients treated with NAT followed by restaging MRI and surgery (NAT, n = 82). The main staging outcomes were dichotomized into T0-T2 vs. ≥T3 and N0 vs. N+, using final pathology as the reference standard. Agreement, Cohen’s kappa, sensitivity, specificity, predictive values, McNemar’s test, and exploratory regression analyses for misclassification were performed. Results: In the overall cohort, agreement was 72.4% for T staging and 73.0% for N staging, with moderate agreement for T (kappa = 0.452) and fair-to-moderate agreement for N (kappa = 0.349). Sensitivity and specificity were 80.3% and 67.0% for T staging and 54.5% and 80.6% for N staging, respectively. T-stage errors were mainly associated with overstaging. In NAT-treated patients, baseline MRI showed markedly poorer agreement with final pathology than restaging MRI, particularly for T stage (45.1% vs. 72.0%). Exploratory analyses did not identify strong or reproducible predictors of misclassification. Conclusions: This real-world study provides a contemporary estimate of MRI-pathology agreement for dichotomized T and N staging in routine RC care. Agreement was moderate, and performance was more consistent for advanced T-category assessment than for nodal staging. These findings support MRI as a practical tool for multidisciplinary risk stratification and highlight the need for continued monitoring of MRI usage and performance in clinical practice.

Diagnostics doi: 10.3390/diagnostics16101480

Authors: Andrei Bojan Maria-Cristina Vladeanu Catalin Pricop Iris Bararu-Bojan Cezar Ilie Foia Simona Eliza Giusca Dan Iliescu Oana Viola Badulescu Codruta Olimpiada Iliescu Halitchi Maria Alexandra Martu Amin Bazyani Manuela Ciocoiu Liliana Georgeta Foia

Background: Gallbladder carcinoma (GBC) represents one of the most aggressive malignancies of the hepatobiliary system, evolving along a continuum from chronic inflammation to preneoplastic lesions and invasive cancer. This progression is frequently associated with gallstones and chronic cholecystitis and shares common pathogenic mechanisms with systemic inflammatory and metabolic disorders. Despite its relatively low incidence, GBC is characterized by poor prognosis, largely due to late-stage diagnosis and limited understanding of its molecular underpinnings. Methods: We conducted an observational study including 60 adult patients with radiologically suspected gallbladder cancer (GBC). Patients with disseminated disease, ongoing oncologic treatment, or synchronous malignancies were excluded. Fasting venous blood samples were collected to evaluate tumor markers and biochemical parameters, including carcinoembryonic antigen (CEA) and carbohydrate antigen CA 19-9. Surgical specimens were analyzed histopathologically and staged according to the European Society for Medical Oncology TNM classification system. Statistical analysis was performed using SPSS software (version 26.0), with appropriate parametric or non-parametric tests applied based on data distribution, and a p-value < 0.05 considered statistically significant. Results: Based on histological findings, patients were stratified into benign gallbladder disease (GBD) and GBC groups. CA 19-9 demonstrated higher mean serum levels with lower variability compared to CEA, suggesting superior sensitivity and diagnostic stability for gallbladder adenocarcinoma. In contrast, CEA levels exhibited greater fluctuation, limiting its reliability as a standalone biomarker. Importantly, the combined use of CA 19-9 and CEA improved diagnostic accuracy, supporting a multimarker approach for better clinical stratification. Our findings highlight the diagnostic value of CA 19-9 as a robust biomarker in GBC and support the integration of combined biomarker panels. Beyond tumor markers, the study identified a strong interplay between systemic inflammation and metabolic comorbidities, with obesity and hypertension significantly associated with chronic gallbladder pathology, and diabetes mellitus contributing to increased risk of acute inflammatory episodes. Elevated inflammatory markers, leukocytosis, and cholestatic enzyme alterations further supported the presence of a systemic inflammatory milieu. Multivariate analysis revealed that C-reactive protein (CRP), as a marker of systemic inflammation, was significantly influenced by a combination of clinical and biochemical variables, including age, hemoglobin, hypertension, amylase, CA 19-9, and CEA, explaining over 50% of its variability and up to 85% in advanced fibrotic changes. Additionally, platelet counts were significantly reduced in adenocarcinoma and correlated specifically with CA 19-9 levels, suggesting a potential link between tumor burden, inflammation, and platelet dynamics. Conclusions: Therefore, the observed associations between chronic inflammation, metabolic dysregulation, and tumor marker expression suggest a potential link between gallbladder carcinogenesis and systemic cardiometabolic pathways, opening new perspectives for early detection and targeted therapeutic strategies.

Diagnostics doi: 10.3390/diagnostics16101479

Authors: Zeinep Avizova Ayan O. Myssayev Yerbolat M. Iztleuov

Background/Objectives: Lung cancer remains a leading cause of cancer-related death, and prognostic assessment relies mainly on TNM staging, which incompletely captures patient heterogeneity. Machine learning (ML) methods may improve survival prediction, but their use in real-world national registries with rigorous validation remains limited. This study aimed to develop ML-derived phenotypes and 1-year mortality risk groups and to evaluate their performance and clinical utility in a national lung cancer cohort from Kazakhstan. Methods: We conducted a retrospective study using a national registry including 13,685 patients. Eight routinely collected predictors were analyzed. K-means clustering was used for exploratory phenotyping. A random survival forest (RSF) model estimated 1-year mortality risk and defined low, intermediate, and high risk groups. Performance was evaluated using temporal validation, cross-validation, and bootstrap correction. Discrimination was assessed using the concordance index, prediction accuracy using the Brier score, and calibration using risk group comparisons. Comparator models included penalized Cox and TNM-only models. Clinical utility was assessed using decision-curve analysis. Results: Two phenotypes showed distinct survival outcomes, although cluster separation was modest. The RSF model showed stable performance (C-index 0.679; corrected 0.663). Risk groups demonstrated strong survival separation (high vs. low: HR 5.66). The RSF model outperformed the penalized Cox (C-index 0.544) and TNM (0.606), with improved accuracy (Brier 0.169 vs. 0.212). Calibration was generally good. Decision-curve analysis showed greater net benefit. Conclusions: An RSF-based model using routine registry data provided robust internally validated risk stratification and improved predictive performance. Clustering results were exploratory. External validation is re-quired before clinical implementation.

Diagnostics doi: 10.3390/diagnostics16101478

Authors: João Pinheiro Beatriz Afonso Emanuel Cortesão de Seiça Rita Gonçalves Luís Ribeiro Joana Reis

Background: Head motion and variability in scan quality remain major methodological challenges in autism neuroimaging. Large multi-site datasets such as ABIDE-II provide a unique opportunity to systematically quantify diagnostic differences in MRI data quality and assess the influence of site-level heterogeneity. Methods: Functional MRI Quality Assessment Protocol (QAP) metrics were combined with phenotypic data from ABIDE-II. Participants were classified as autistic (ASD) or typically developing (TD). Key quality metrics—including mean framewise displacement (mFD), proportion of volumes exceeding 0.20 mm (FD > 0.20), signal-to-noise ratio (SNR), and entropy focus criterion (EFC)—were analyzed alongside age, sex, IQ, and site. Group differences were evaluated using non-parametric tests and linear mixed-effects models with site as a random factor. Additional analyses examined site-level heterogeneity and the impact of quality-control (QC) thresholds on sample composition. Results: The final sample included 1277 participants (579 ASD; 698 TD) across 14 sites. ASD participants exhibited significantly greater head motion (median mFD = 0.101 vs. 0.081 mm; p < 1 × 10−10) and modest reductions in signal quality (lower SNR, higher EFC). Elevated motion in ASD was observed in 12 of 14 sites, although effect sizes varied substantially. Mixed-effects models confirmed that diagnosis remained a significant predictor of motion after adjusting for covariates. In contrast, signal-quality differences were small and largely explained by site effects. Simulated QC procedures disproportionately excluded ASD participants, with exclusion rates up to 31% compared to 18% in TD. Conclusions: ASD participants show consistently higher head motion, while signal-quality differences are minimal and largely site-driven. Standard QC procedures disproportionately exclude ASD individuals, highlighting the need for improved motion handling and more balanced quality-control strategies in multi-site studies.

Diagnostics doi: 10.3390/diagnostics16101477

Authors: Federica Pezzuto Martina Maione Chiara Giraudo Marta Sbaraglia Angelo Paolo Dei Tos Fiorella Calabrese

Pulmonary nodules detected in patients with a history of malignancy are often clinically presumed to represent metastatic disease until proven otherwise. Granular cell tumor (GCT) is an uncommon, usually benign neoplasm of presumed Schwannian origin, which rarely occurs in the lung. Our aim is to emphasize the diagnostic challenges and the crucial role of histopathology in preventing overtreatment in oncology patients. Herein, we report the case of a 56-year-old woman with a previous history of papillary renal cell carcinoma diagnosed one year earlier, staged as pT1, WHO/ISUP grade 2, and treated with partial nephrectomy, with no evidence of residual disease or distant metastases at follow-up. During routine surveillance, she developed a solitary pulmonary nodule. Chest computed tomography (CT) showed a 12 mm solid nodule in the left upper lobe which was then further investigated with a positron emission tomography with 2-[18F] fluoro-2-deoxy-D-glucose [(18F)-FDG PET/CT, revealing a low glucidic uptake (SUVmax 4 and SUV mean 1.4). Endobronchial ultrasound-guided biopsy was non-diagnostic. Given the patient’s oncological history, the solid appearance on CT, and the mild FDG uptake, metastatic disease could not be excluded, and a parenchyma-sparing diagnostic wedge resection was performed. Histology showed a well-circumscribed proliferation of epithelioid cells with abundant granular eosinophilic cytoplasm and bland nuclei. Immunohistochemistry demonstrated diffuse S100 and CD68 positivity, supporting the diagnosis of primary pulmonary granular cell tumor. This case underscores the critical role of histopathological evaluation in the assessment of solitary pulmonary nodules, emphasizing that lesions identified during oncologic surveillance are not invariably indicative of malignancy.

Diagnostics doi: 10.3390/diagnostics16101476

Authors: Maja Aleksandra Oksentowicz Maria Sztachelska Violetta Dymicka-Piekarska

Background: Patients with COVID-19 often develop COVID-19-Associated Coagulopathy (CAC)—an imbalance between procoagulant and anticoagulant pathways resulting from the uncontrolled inflammatory response triggered by SARS-CoV-2 infection. This study aims to investigate the impact of a hematological and inflammatory parameter—the platelet-to-lymphocyte ratio (PLR)—on the severity and mortality of COVID-19. Methods: We conducted a comprehensive search of the PubMed database and yielded 75 articles published in the period of 2020–2025, of which 20 studies that evaluated the prognostic value of PLR on hospital admission in COVID-19 patients were included. The review particularly focuses on ROC analyses and reported AUC values. Results: A total of 20 studies were analyzed, including 13 studies assessing disease severity and 14 studies evaluating mortality. Higher PLR values have been observed in patients with a more severe course of COVID-19 compared to those with milder disease, and in non-survivors compared to survivors. However, the literature shows inconsistency regarding the diagnostic utility of PLR based on ROC curve analysis. The reported AUC values ranged from 0.559 to 0.811 for disease severity differentiation and from 0.474 to 0.758 for mortality, which may be related to the heterogeneity of the study populations included in the analysis. Conclusions: PLR may not serve as a direct bridge between inflammation and coagulation in COVID-19-Associated Coagulopathy, but it is indirectly linked to disease severity and mortality, as it reflects changes in both platelet and lymphocyte counts. It is a complementary marker that may assist clinicians in assessing COVID-19 patients but still requires further investigation.

Diagnostics doi: 10.3390/diagnostics16101475

Authors: Alvita Vilkeviciute-Petraite Akvile Bruzaite Dzastina Cebatoriene Dalia Zaliuniene Rokas Lukosevicius Jurgita Skieceviciene Juozas Kupcinskas Rasa Liutkeviciene

Background/Objectives: This study explores the roles of kynurenine and 5-hydroxytryptophan (5-HTP) in modulating gut microbiota and their potential implications for exudative age-related macular degeneration (AMD). By examining the interplay between these metabolites and the microbiome, we aim to uncover novel pathways that may influence the pathogenesis of AMD. Understanding these associations could lead to innovative therapeutic approaches for managing this leading cause of vision loss in the elderly. To investigate the roles of kynurenine and 5-HTP, alongside the composition of the nasopharyngeal microbiota, in patients with exudative AMD. Methods: Blood metabolite profiling was performed using LC–MS–based metabolomics. Metabolites were extracted with cold methanol/water containing internal standards, filtered through a 10 kDa cutoff filter, separated on a ZIC-HILIC HPLC column, and detected using an Orbitrap mass spectrometer. Metabolites were identified using MZmine 2 software. Results: Patients with exudative AMD exhibited a profound systemic shift in tryptophan metabolism, characterized by significantly lower plasma levels of 5-HTP and higher levels of kynurenine compared to control subjects (p < 0.001 for both). Logistic regression analysis confirmed that both metabolites were independent predictors of AMD status; higher kynurenine levels were associated with increased disease probability, while higher 5-HTP levels demonstrated a protective effect. The kynurenine/5-HTP ratio emerged as a robust biomarker, achieving an area under the curve (AUC) of 0.85 with an optimal threshold of 3.43 (74.1% sensitivity, 84.4% specificity). When integrated with age and gender, the diagnostic performance of the model reached an excellent AUC of 0.92. After adjusting for demographic factors, the kynurenine/5-HTP ratio remained a potent independent risk factor, with each unit increase associated with a 6.30-fold increase in the odds of exudative AMD. Conclusions: Exudative AMD is characterized by a shift in tryptophan metabolism toward the kynurenine pathway, with decreased 5-HTP, increased kynurenine, and an elevated kynurenine/5-HTP ratio. This ratio showed a strong independent association with AMD and excellent diagnostic performance, highlighting its potential as a biomarker and its role in disease pathogenesis.

Diagnostics doi: 10.3390/diagnostics16101474

Authors: Nabeel Alzahrani Atheer Alghamdi Anmar Yankasar Nawal Alyami Hoda Abanmi Bassam Alwan Lana Alzamil Sameera Al Johani

Background/Objectives: Urine culture processing is labor-intensive and prone to operator-dependent variability. This study compared total laboratory automation (TLA; BD Kiestra™) with manual urine culture processing in terms of workflow efficiency, diagnostic performance, and operator variability. Methods: Three hundred midstream urine specimens were processed using manual and automated workflows, stratified by technologist experience (expert ≥10 years; non-expert <2 years) and shift. Metrics included setup time, cleanup time, and total staff time (TST). Colony-forming unit (CFU) recovery using 1 µL manual inoculation, 10 µL manual inoculation, and 10 µL TLA inoculation of 20 known positive specimens was compared. Diagnostic performance was assessed against the 1 µL manual reference using serially diluted specimens at a ≥105 CFU/mL threshold. Results: TLA reduced the setup time from 10 min 10 s to 2 min 05 s for experts and from 13 min 37 s to 2 min 20 s for non-experts (79–83% reduction). TST decreased from 11 min 06 s to 2 min 30 s and from 14 min 37 s to 3 min 15 s, respectively (77–78% reduction). Cleanup time showed smaller reductions that did not reach statistical significance in the paired analysis. Manual processing showed greater operator-dependent variability, which TLA substantially reduced. CFU recovery was concordant in high-burden specimens, with method-dependent differences in routine diagnostic samples. Conclusions: TLA improves urine culture workflow efficiency, reduces operator-dependent variability, and shows concordant semi-quantitative performance compared to the standard manual reference within the limits of a proof-of-concept design, supporting its implementation to enhance consistency and throughput in clinical microbiology laboratories.

Diagnostics doi: 10.3390/diagnostics16101473

Authors: Madalina-Ianca Suba Gheorghe-Bogdan Hogea Varga Norberth-Istvan Florina Cristiana Lucaciu Camelia Corina Pescaru Ovidiu Rosca Daniela Gurgus Bogdan Rotea Andra Rotea Ahmed Abu-Awwad Anca Mihaela Bina Daniel Pop Simona-Alina Abu-Awwad

Background/Objectives: Sepsis is a dynamic clinical syndrome characterized by a rapidly evolving inflammatory response, where early identification of patients at risk for adverse outcomes remains a major challenge. While inflammatory biomarkers are widely used, their prognostic value at baseline is limited. This study aimed to evaluate whether early changes in inflammatory biomarkers, particularly the neutrophil-to-lymphocyte ratio (ΔNLR), provide additional prognostic value in predicting short-term outcomes in patients with sepsis. Methods: A retrospective longitudinal observational study was conducted, including 168 adult patients admitted with sepsis at a tertiary infectious diseases hospital. Inflammatory biomarkers (CRP, procalcitonin, leukocyte subpopulations, and NLR) were assessed at admission and at 48–72 h. Early changes (Δ values) were calculated and analyzed in relation to a composite adverse outcome, including ICU admission, vasopressor requirement, mechanical ventilation, or in-hospital mortality. Logistic regression and ROC curve analyses were used to evaluate predictive performance. Results: Patients with adverse outcomes had significantly higher baseline inflammatory markers and severity scores. Early reductions in CRP and NLR were more pronounced in survivors, whereas non-survivors showed persistently elevated or minimally decreasing values. In multivariate analysis, ΔNLR remained independently associated with in-hospital mortality (OR 0.91, 95% CI 0.84–0.98, p = 0.015), alongside Sequential Organ Failure Assessment (SOFA) score and septic shock. ΔNLR demonstrated better discriminative performance (AUC 0.74) compared to baseline markers and improved predictive accuracy when combined with SOFA score (AUC 0.81). Higher baseline NLR quartiles were associated with a stepwise increase in adverse outcomes. Conclusions: Early changes in inflammatory biomarkers, particularly ΔNLR, provide clinically relevant prognostic information beyond baseline measurements and severity scores in sepsis. Dynamic assessment of immune response may improve early risk stratification and support more individualized clinical decision-making.

Diagnostics doi: 10.3390/diagnostics16101472

Authors: Anikó Smudla Herbert Schöchl Andreas Calatzis Csikós Richárd Gergely János Fazakas

Viscoelastic testing (VET) is widely used to guide hemostatic therapy in patients with coagulopathy. One important application is the detection of fibrinolysis, defined as a reduction in clot amplitude after maximum clot firmness (MCF), quantified as maximum lysis (ML). Low ML values have recently been associated with adverse outcomes in trauma and sepsis. However, the biological basis of low ML remains unclear. Objective: To determine whether low ML values reflect reduced plasmin-mediated fibrinolysis in tissue factor (TF) activated viscoelastic assays (EX-assay). Methods: A total of 120 healthy adults (52.5% female; mean age 38.2 ± 14.1 years) were studied. EX-assay without fibrinolysis inhibition were compared with assays containing the antifibrinolytic agent tranexamic acid (AP-assay). VET parameters obtained with and without fibrinolysis inhibition were compared using paired analyses, Pearson correlation, and Bland–Altman methods. Results: Clot firmness at 10 min (CA10) was similar with or without fibrinolysis inhibition; although MCF differed statistically, the difference was clinically negligible. ML ranged from 1% to 13% in both assays, with nearly identical mean values (5.9 ± 2.6% vs. 6.0 ± 2.6%). Correlation analysis demonstrated strong agreement for CA10, MCF, and ML between assays, and Bland–Altman analysis confirmed minimal bias for ML. Conclusions: Low ML values in TF-triggered viscoelastic assays were unaffected by tranexamic acid, suggesting that they are unlikely to reflect plasmin-mediated fibrinolysis. These findings support the contribution of alternative mechanisms, such as platelet-mediated clot retraction.

Diagnostics doi: 10.3390/diagnostics16101471

Authors: Adelina Amalia Ardelean Laura Alexandra Nussbaum Andrei Brînzeu

Somatosensory mismatch negativity (sMMN) constitutes an electrophysiological marker that initially reflects preattentional processing and subsequently indexes automatic somatosensory deviance detection. While its application in adult populations is gradually expanding, the establishment of a standardized and reproducible methodology for eliciting and analyzing sMMN in pediatric populations remains uncertain. To determine whether the published literature provides a clear, consistent, and standardized methodology for sMMN assessment in individuals under 18 years. A search was conducted in PubMed (11), Scopus (6), Web of Science (6), DOAJ (1), Europe PMC (6), Embase (0), ClinicalKey (0), Cochrane Library (0) and ClinicalTrials.gov (0) database from inception to 18 August 2025. Eligible studies included research assessing sMMN using somatosensory oddball paradigms in participants <18 years. Inclusion criteria (participants younger than 18 years, the use of the oddball paradigm to evaluate somatosensory mismatch negativity, and clinical reports, single-case reports or experimental studies including both typically developing children and children with neurological conditions, published in English), and exclusion criteria (exclusivity for adult participants, and narrative reviews or editorials) were defined a priori, as well as the screening procedures and quality assessment methods. Two reviewers independently performed study selection and data extraction, with a third reviewer resolving disagreements. Risk of bias was assessed using the MMAT (mixed methods appraisal tool). Due to substantial heterogeneity in paradigms and outcome reporting, results were synthesized narratively. Four studies met inclusion criteria. Methodological diversity was pronounced across everything except task type that was passive. There is not a consensus regarding stimulation parameters. Risk of bias assessment revealed frequent concerns related to incomplete reporting and variability in analytic choices. The small number of studies, inconsistent methodological reporting, and absence of harmonized protocols limited comparability. Current evidence does not support the existence of a standardized methodology for assessing sMMN in children. Future studies should adopt harmonized stimulation paradigms and transparent, reproducible reporting standards to enable cross-study comparability and clinical translation.

Diagnostics doi: 10.3390/diagnostics16101470

Authors: Jihyun Chun Haeyoun Kang Heewon Chung Jae-Myung Jang Jangwon Seo Taegyu Kim Woohyun Lee Cheolhong Park Mingi Hong Han-Mac Brian Kim Messi H. J. Lee Kyongseok Jang Chan Kwon Jung Sang Wun Kim Ahwon Lee

Background/Objectives: Ovarian epithelial cancers (EOCs) comprise heterogeneous subtypes with distinct clinical outcomes, making accurate histological subtyping essential for prognosis and treatment planning. Although deep learning using digitized hematoxylin and eosin (H&E) whole-slide images (WSIs) is now widely used, its application to ovarian cancer diagnosis remains limited. Methods: In this multicenter study, we analyzed 319 H&E-stained slides from 152 patients with surgically resected EOC. An attention-based multiple instance learning (MIL) framework built on a pathology-specific foundation model (UNI) was used. WSIs were divided into 512 × 512-pixel patches at 40× magnification, and slide-level classification were generated through attention-based aggregation of patch-level feature, followed by patient-level prediction. External validation was performed specifically on the high-grade serous carcinoma (HGSC) cases from The Cancer Genome Atlas (TCGA) dataset. Results: The model achieved strong performance, with slide-level and patient-level accuracies of 0.918 and 0.900, respectively, on the test set. In five-fold cross-validation, the mean slide-level AUC was 0.990 (95% CI: 0.983–0.997), and the patient-level AUC was 0.993 (95% CI: 0.989–0.996), indicating consistent results. External validation on TCGA HGSC cases showed robust generalizability, with slide-level and patient-level accuracies of 0.794 and 0.898. F1-scores ranged from 0.832 to 1.000 at the slide-level and from 0.831 to 0.966 at the patient-level, with particularly strong performance for HGSC and clear-cell carcinoma. Conclusions: These findings demonstrate the feasibility of deep learning-based models for histological subtyping of EOC using H&E-stained WSIs. This approach may help pathologists achieve more accurate and consistent histological diagnoses of EOC.

Diagnostics doi: 10.3390/diagnostics16101469

Authors: Adelina Baloi Dorel Sandesc Talida Georgiana Cut Radu Caprariu Dorin Novacescu Cristina-Stefania Dumitru Alina Cristina Barb Raluca Dumache Pavel Banov Victoria Birlutiu Voichita Elena Lazureanu Flavia Zara

Background/Objectives: Hungry bone syndrome (HBS) is a frequent and potentially life-threatening complication following parathyroidectomy (PTX) for secondary hyperparathyroidism (SHPT) in dialysis patients, yet existing prediction tools offer limited discriminative accuracy. This study aimed to develop and internally validate an interpretable machine learning (ML) framework for preoperative HBS prediction and to derive a pragmatic bedside risk score from ML-derived feature importance. Methods: Ninety end-stage renal disease patients who underwent PTX for drug-refractory SHPT at a single center (2019–2023) were analyzed. Eight supervised ML classifiers were trained on 24 preoperative features (19 raw variables plus 5 engineered features) and evaluated under 5-fold stratified cross-validation repeated 10 times. SHapley Additive exPlanations (SHAP) analysis was applied for model interpretability, and a composite bedside risk score was constructed from SHAP-derived feature rankings. Results: HBS occurred in 41 patients (45.6%). Random forest achieved the numerically highest discrimination among multi-feature models (AUC = 0.933 ± 0.065), outperforming previously published models, though univariate alkaline phosphatase (ALP) alone achieved a comparable cross-validated AUC of 0.958. ALP overwhelmingly dominated all predictors (mean |SHAP| = 3.37, exceeding the next-ranked feature by approximately 6.5-fold). Partial dependence analysis revealed a sigmoid-shaped ALP–HBS relationship with a critical inflection zone between 250–350 U/L, and SHAP dependence plots demonstrated that total parathyroidectomy amplifies ALP-mediated risk. A SHAP-guided composite bedside risk score (range 0–9) achieved an AUC of 0.883, with observed HBS rates rising monotonically from 0% (score 0) to 100% (score ≥ 6). Decision-curve analysis showed that univariate ALP and the multi-feature pipeline yielded comparable net benefit, with ALP preferable in the high-sensitivity regime and the multi-feature model preferable at high-specificity thresholds; net reclassification improvement was negative for the multi-feature model vs. univariate ALP, supporting the framework’s role as an interpretive rather than discriminative advance. Conclusions: An interpretable ML framework substantially improves HBS prediction over conventional models, confirms ALP as the overwhelmingly dominant predictor through a nonlinear dose–response relationship, and yields a clinically interpretable bedside risk score that, pending external validation, may support preoperative risk stratification.

Diagnostics doi: 10.3390/diagnostics16101466

Authors: Nicola Guindani Mario Gaffuri Pietro Andrea Bonaffini Clarissa Valle Alessandro Caruso Greta Carioli Francesca Fenili Rosalia Zangari Sandro Sironi Federico Chiodini Claudio Carlo Castelli

Objectives: The association between osteonecrosis (ON) and Coronavirus Disease of 2019 (COVID-19) was reported early during the pandemic. ON of the femoral head (ONFH) is particularly problematic, as it may destroy the joint and lead to arthroplasty, although early diagnosis and treatment might mitigate its progression. The aim of the present study was to quantify the prevalence of symptomatic and asymptomatic ONFH in patients with severe COVID-19 treated with high doses of corticosteroids during the first pandemic wave. Methods: For this prospective, observational, monocentric cohort study, patients were selected according to the risk factors described for severe acute respiratory syndrome coronavirus in 2002–2004 (SARS-1): young males (<61 years old), high cumulative cortisone doses (≥2 g), severe disease, and followed up clinically and with magnetic resonance imaging. ONFH was classified with the ARCO classification. Results: Out of 1944 patients admitted for COVID-19 from 23 February to 21 May 2020, 856 of 1944 were treated in ICU; 30/1944 were selected according to the inclusion criteria and 27 of 30 were enrolled. The mean age at admission was 54 years (range, 42–60). The mean dose of cumulative cortisone was 6.25 g (range, 2–16). A total of 4/27 (15%) patients had ONFH; only 2 of 4 (50%) were symptomatic, including 1 with multiple ON of major joints. Conclusions: A high-risk cohort of patients with COVID-19 and high doses of corticosteroids had a 15% rate of ONFH, and 2 years after the event, 50% of them were asymptomatic. For those patients, relying solely on clinical evaluation would risk underestimating ONFH, potentially influencing treatment and outcomes. Moreover, other joints might develop ON. The data collected in the present study can be considered for the management of long-COVID. The association between severe COVID-19, high doses of corticosteroids and ONFH suggests the need for focused clinical and magnetic resonance imaging, considering the high rate of asymptomatic patients.

Diagnostics doi: 10.3390/diagnostics16101468

Authors: Aurelian Mihai Ghiță Daniela Adriana Iliescu Larisa Adriana Ilie Ana Cristina Ghiță

Background/Objectives: Corneal endothelial damage remains a key concern following phacoemulsification. This study aimed to quantify early postoperative changes in endothelial cell density metrics after cataract surgery in a Romanian population and to identify preoperative and intraoperative predictors of endothelial cell loss at 1 week and 1 month postoperatively. Methods: We conducted a retrospective observational study of 137 eyes that underwent standard phacoemulsification with intraocular lens implantation at Ocularcare Ophthalmology Hospital in Bucharest, Romania. Preoperative data included age, sex, and biometric parameters: anterior chamber depth (ACD), axial length (AL), and central corneal thickness (CCT). Corneal endothelium was assessed by specular microscopy preoperatively and at 1 week and 1 month postoperatively, with measurements of endothelial cell density (CD), number of analyzed cells (No), average cell size (ACS), minimum and maximum cell size (MinCS, MaxCS), and cell size variability (SD). Intraoperative parameters included average ultrasound energy (AVE) and actual phacoemulsification time (APT). Associations between demographic, biometric, and surgical variables and postoperative endothelial changes were analyzed using univariable and multivariable regression models. Results: In 137 eyes, mean CD decreased from 2401.99 ± 342.57 cells/mm2 preoperatively to 2144.38 ± 449.92 at 1 week and 2053.15 ± 471.13 at 1 month. CCT increased from 534.64 ± 38.01 µm to 548.70 ± 41.34 µm at 1 week and remained higher than baseline at 1 month (545.67 ± 42.91 µm). Endothelial remodeling was reflected by significant increases in ACS, MaxCS, and SD, while No and MinCS showed no significant change. In adjusted models, lower postoperative CD was independently associated with shallower ACD and lower baseline CD at both timepoints, whereas higher AVE was associated with lower postoperative CD at 1 week but not at 1 month; sex was not independently associated with postoperative CD. Conclusions: In this Romanian cohort, phacoemulsification was associated with significant early endothelial cell loss measurable within the first postoperative month. The magnitude of CD reduction was influenced by both baseline patient ocular characteristics (ACD) and intraoperative phacoemulsification parameters, particularly ultrasound energy (AVE). These findings support the incorporation of preoperative biometric assessment and intraoperative ultrasound minimization strategies to reduce endothelial risk.

Diagnostics doi: 10.3390/diagnostics16101467

Authors: Mario Bonomini Valeria Vezzani Michele Rossini Lorenzo Di Liberato Liborio Stuppia Valentina Gatta

Background and Clinical Significance: Autosomal dominant tubulointerstitial kidney disease caused by a mutation in the uromodulin gene (ADTKD-UMOD) is a rare kidney disorder characterized by progressive tubulointerstitial damage and a slowly progressive loss of renal function. ADTKD is often under-recognized in the clinical setting. Diagnosis of ADTKD-UMOD can be challenging due to its nonspecific symptoms and is confirmed by genetic testing alone. Case presentation: We report the case of a 42-year-old male patient referred for evaluation of renal dysfunction, which was accidentally discovered during routine laboratory checks. He had no significant medical history and no known family history of kidney disease or gout. Physical examination was unremarkable. Renal dysfunction was confirmed, with serum creatinine at 1.44 mg/dL and eGFR at 59.5 mL/min/1.73 m2. Urinalysis was within physiological limits, proteinuria being 75 mg/day. Uric acid was mildly elevated (7.5 mg/dL) without a history of gout. Other laboratory findings, including autoantibodies, were in the normal range. The patient underwent a kidney biopsy, though it was not diagnostic, showing mild focal tubular atrophy and interstitial fibrosis without glomerular involvement. Immunofluorescence staining was negative for complement and immunoglobulins. Given the above nonspecific findings, the patient was suspected of having possible ADTKD. Genetic investigation using a clinical exome next-generation sequencing approach identified a novel heterozygous missense variant in the UMOD gene (c.409T>C; p.Cysteine137Arginine (p.Cys137Arg)) that is likely pathogenic. The patient is under regular clinical-laboratory monitoring. After one year, his overall health is good, renal function is stable with no proteinuria, and uric acid is mildly increased without gout attacks. Conclusions: Increased clinical awareness is crucial for detecting ADTKD-UMOD. Genetic testing can help to resolve clinical diagnostic challenges in patients with unexplained decreased kidney function.

Diagnostics doi: 10.3390/diagnostics16101465

Authors: Ivana Sekulovic-Radovanovic Ilya V. Sivokozov Nensi Lalic Spasoje Popevic

Hemoptysis is a potentially life-threatening phenomenon with a wide range of underlying causes. While most episodes are linked to common conditions such as infections, malignancy, or pulmonary embolism, a proportion of cases are due to unusual and often unexpected etiologies. This narrative review summarizes published case reports, series, and observational studies describing rare causes of hemoptysis, including vascular malformations, congenital anomalies, benign tumors, systemic diseases, and unusual infections. These conditions are frequently overlooked, which may delay recognition and appropriate management. The reviewed examples highlight the variety of diagnostic challenges and the broad spectrum of therapeutic strategies that may be required, ranging from endovascular procedures and surgery to targeted medical therapy. Despite advances in diagnostic methods, a subset of patients remain classified as having idiopathic or cryptogenic hemoptysis. For this reason, clinicians should keep a broad differential diagnosis in mind and remain aware of rare but clinically important entities. Awareness of these uncommon presentations and individualized patient management are essential for improving outcomes and avoiding missed critical diagnoses.

Diagnostics doi: 10.3390/diagnostics16101464

Authors: Argun Ege Türkün Müslim Ege Kalender Murat Kurt Servet Doğan

Background/Objectives: The aim of this study was to evaluate and compare the accuracy, reliability, and time efficiency of a convolutional neural network (CNN)-based deep learning model with manual annotation in the identification of soft tissue landmarks on two-dimensional (2D) facial images for orthodontic applications. Materials and Methods: Three-dimensional (3D) facial scans were obtained from 100 participants (50 females, 50 males) aged 18–25 years using the Revopoint Pop2 3D Scanner. Frontal and profile 2D images were extracted from the 3D models. Manual landmark identification was performed by a single investigator using LabelMe software, marking 22 landmarks on frontal images and 15 landmarks on profile images. A novel CNN model was developed and trained on these manually annotated images. The model’s automatic landmark identifications were compared with manual annotations in terms of positional error, identification time, and reproducibility. Results: The CNN model achieved a mean localization accuracy of 96.07%. The mean prediction error ranged from 2.3% to 4.5% across various anatomical points. Trichion, Menton, and Gonion points exhibited relatively higher error rates. The model significantly reduced the annotation time compared to manual identification (manual method: 237 s per image). Intra-observer reliability analysis demonstrated excellent agreement for manual landmarking (ICC: 0.85–0.95). The AI model provided consistent predictions for identical inputs. Conclusions: The deep learning-based model demonstrated comparable accuracy to manual landmark identification while significantly improving the annotation speed and reproducibility. These results suggest that CNN-based systems offer a promising alternative for clinical orthodontic analysis and digital workflow integration.

Diagnostics doi: 10.3390/diagnostics16101463

Authors: Ivan Maleš Anđela Šarić Ivan Lovrinčević Joško Božić Zenon Pogorelić

Background/Objectives: Intraoperative assessment guides the immediate postoperative management of acute appendicitis, whereas histopathological confirmation becomes available only after key clinical decisions have been made. This study evaluated the agreement between intraoperative and histopathological grading of acute appendicitis and compared their associations with postoperative outcomes, particularly length of hospital stay (LOS) and duration of antibiotic therapy. Methods: This retrospective single-center study included pediatric and adult patients who underwent appendectomy for suspected acute appendicitis at the University Hospital of Split between 1 January 2020 and 31 December 2025. After exclusion criteria were applied, 2279 patients were included. Agreement between intraoperative and histopathological classifications was assessed using Cohen’s kappa and weighted kappa. Associations with postoperative outcomes were examined using Kendall’s tau correlation, bootstrap comparison between age groups, Kruskal–Wallis testing with Bonferroni-adjusted post hoc analyses, adjusted negative binomial regression for length of hospital stay, zero-inflated negative binomial regression for total antibiotic duration, and Firth penalized logistic regression for binary outcomes. Results: Overall concordance between intraoperative and histopathological grading was 74.0%. Agreement was moderate by unweighted Cohen’s kappa (0.539) and substantial by weighted kappa (0.643), with intraoperative grading more often overestimating than underestimating histopathological severity. Intraoperative severity showed stronger correlations than histopathological severity with LOS (τ = 0.347 vs. 0.207) and total duration of antibiotic therapy (τ = 0.331 vs. 0.224). Both outcomes showed a non-linear pattern, with patients with a negative appendix having a longer hospital stay and greater antibiotic exposure than those with phlegmonous appendicitis, while advanced disease was associated with the greatest treatment burden. Thirty-day readmission was uncommon and not associated with severity. Conclusions: Agreement between intraoperative and histopathological grading was moderate to substantial. Intraoperative grading showed stronger associations with immediate postoperative outcomes than histopathological grading, reflecting its role as the primary driver of clinical decision-making in the immediate postoperative period. These findings do not diminish the diagnostic value of histopathological examination, which remains essential for confirmation and detection of unexpected pathology.

Diagnostics doi: 10.3390/diagnostics16101461

Authors: Simona Wójcik Monika Tomaszewska Anna Rulkiewicz

Background/Objectives: Obesity is a chronic, relapsing disease with a widening gap between clinical need and the availability of specialist care. Artificial intelligence (AI) may enable earlier risk detection, more precise phenotyping, and scalable behavioural support across obesity treatment pathways. This narrative review synthesises contemporary AI applications across the obesity care continuum and evaluates their translational readiness. Methods: A targeted search of PubMed/MEDLINE and Google Scholar (January 2024–January 2026) was conducted, complemented by citation chaining. Evidence was synthesised across four domains: (1) risk prediction and screening, (2) environmental and behavioural determinants, (3) multimodal phenotyping and precision stratification, and (4) AI-enabled lifestyle interventions and behavioural coaching (AIBC). Results: Electronic health record (EHR)-based models demonstrate clinically useful discrimination for early risk identification. Multimodal approaches refine stratification beyond body mass index (BMI)-centric classification. AI-enabled behavioural coaching (AIBC) platforms show emerging evidence of clinically meaningful weight loss, including non-inferiority to human coaching; however, long-term effectiveness, generalisability, and equity remain insufficiently established. Conclusions: AI is positioned to become a core enabler of personalised obesity pathways. Safe translation requires external validation, bias auditing, transparent reporting, human oversight, and post-deployment surveillance aligned with clinical guidelines and regulatory expectations.

Diagnostics doi: 10.3390/diagnostics16101462

Authors: Marin Davidović Juraj Kolak Josip Basić Anita Zenko Sever Lucija Brkić Barbara Kolak Igor Petrović Hrvoje Silovski

Background: Acute cholecystitis is one of the most common acute diseases of the biliary system and a frequent reason for emergency hospital admission and surgical treatment. More severe forms are associated with a higher need for intensive care, more frequent use of open surgery, and less favourable outcomes. Age and chronic comorbidity burden may play an important role in determining disease severity. The age-adjusted Charlson Comorbidity Index (CCI-Age) is a simple and widely used tool for integrated assessment of age and comorbidity burden, but its role in acute cholecystitis is not sufficiently defined. Methods: Data for this study were collected by retrospective analysis of hospital records from the hospital information system of the University Hospital Centre Zagreb. Patients treated conservatively were excluded. The association of age and CCI-Age with the severity of the clinical presentation of acute cholecystitis was analysed using dichotomised clinical variables and comparative statistical methods. Results: The results showed that age and the presence of chronic diseases were strongly associated with the severity of the clinical presentation of acute cholecystitis. Older patients and those with a greater burden of chronic comorbidities significantly more often developed more severe forms of the disease. Among chronic diseases, peripheral vascular disease, diabetes mellitus, and chronic renal disease showed the strongest association with more severe clinical presentation. Conclusions: Age and CCI-Age were strongly associated with the severity of the clinical presentation of acute cholecystitis. CCI-Age may represent a useful tool for early clinical risk stratification and support therapeutic decision making in everyday surgical practice.

Diagnostics doi: 10.3390/diagnostics16101460

Authors: Sanjana Arun Eujung Park Katja Klosterman Carissa Zhu Ronak Arun Palmer Wrigley Stratton Hamsa Gangaswamiah

Background/Objectives: Large language models (LLMs) are increasingly applied to medical image interpretation; however, their diagnostic accuracy and reliability in musculoskeletal radiology remain uncertain. This study evaluates the diagnostic performance and confidence calibration of LLMs in detecting and classifying bone tumors on radiographs. Methods: This retrospective observational study analyzed a dataset of 257 radiographs with confirmed diagnoses obtained from Radiopaedia, including normal studies and a spectrum of benign and malignant bone tumors. Cases were selected to ensure representation across multiple tumor types. Three LLMs (ChatGPT 5.3, X-ray Interpreter GPT-4.1, and X-ray Interpreter Gemini) evaluated each image using a standardized prompt assessing abnormality detection, tumor detection, classification, and confidence. Outcomes included diagnostic accuracy, false positive abnormality rates, false negative rates, tumor hallucination rates, and confidence calibration. Results: Abnormality detection was high across models, with Gemini demonstrating the highest sensitivity (up to 100%). Tumor detection was strongest in lesions with characteristic features, including osteosarcoma and osteochondroma. False negative rates varied substantially, with GPT-4.1 demonstrating the highest rate (29.9%), followed by ChatGPT (24.8%) and Gemini (6.6%). Primary diagnostic accuracy was highest for osteosarcoma in GPT-4.1 (80%), while ChatGPT 5.3 performed best in benign lesions, including osteochondroma (84.6%) and non-ossifying fibroma (76.9%). Tumor subtype classification remained limited across all models and was poorest for Ewing sarcoma (0% in ChatGPT and GPT-4.1; 10.3% in Gemini). False positive abnormality rates were highest in GPT-4.1 (40.7%), followed by Gemini (25.9%) and ChatGPT (13.5%). Tumor hallucination occurred only in Gemini (12.3%). All models demonstrated confidence miscalibration, with higher confidence observed in incorrect predictions and in tumor-negative cases. Conclusions: LLMs demonstrate strong performance in detecting radiographic abnormalities but remain limited in tumor subtype classification, particularly for diagnostically challenging lesions such as Ewing sarcoma. Elevated false positive and false negative rates, along with systematic overconfidence—especially in GPT-4.1—highlight important limitations for clinical use. These findings support the role of LLMs as adjunctive tools rather than independent diagnostic systems.

Diagnostics doi: 10.3390/diagnostics16101459

Authors: Wiktoria Narloch Marta Jaskulak Klaudia Antoniak-Pietrynczak Katarzyna Zorena

Background/Objectives: Obesity is a complex metabolic disorder associated with chronic low-grade inflammation, insulin resistance, and increased risk of metabolic complications. Traditional measures, such as body mass index (BMI), may not detect early metabolic disturbances. Myokines and cytokines, including irisin, C-C Motif Chemokine (CCL2), interleukin-1β (IL-1β), interleukin-6 (IL-6), and interleukin-15 (IL-15), have been proposed as potential biomarkers. This study aimed to investigate the relationships between these biomarkers and metabolic parameters in adults with varying BMI. Methods: Fifty-one adults (mean age 38 ± 11 years) were stratified by BMI into normal weight, overweight, and obese groups. Serum irisin, CCL2, IL-1β, IL-6, and IL-15 concentrations were measured along with metabolic parameters, including insulin, HOMA-IR, C-peptide, and visceral fat. Statistical analyses included Pearson’s correlation, Kruskal–Wallis ANOVA with Bonferroni correction, and subgroup analyses for insulin resistance (HOMA-IR ≥ 2.5). Results: Irisin concentrations were significantly higher in overweight and obese participants compared with normal-weight individuals (p < 0.001) and positively correlated with insulin (r = 0.77), HOMA-IR (r = 0.63), C-peptide (r = 0.71), and BMI (r = 0.54). In contrast, IL-6 and IL-15 levels did not differ significantly across BMI groups, although IL-15 showed a borderline increase in insulin-resistant individuals (p = 0.048). Both IL-1β and CCL2 were significantly elevated across increasing body-weight categories and showed strong positive correlations with measures of adiposity, visceral fat, and insulin resistance; however, neither marker differed significantly when participants were stratified by insulin-resistance status. Additionally, multivariable linear regression identified irisin as the only independent predictor of insulin resistance, while CCL2 was the strongest predictor of BMI. Principal component analysis (PCA) revealed two dominant components separating metabolic (irisin, HOMA-IR, insulin, BMI) and inflammatory (IL-1β, CCL2) profiles, supporting the distinction between metabolic and inflammatory pathways in obesity. Conclusions: Irisin appears to be a sensitive associative marker of metabolic dysregulation associated with increased body mass and insulin resistance. In contrast, IL-1β and CCL2 reflect obesity-related inflammatory burden rather than early metabolic changes, while IL-6 and IL-15 did not reflect early metabolic alterations in this study. Together, these findings suggest that irisin may serve as an associative biomarker for identifying individuals at risk of obesity-related metabolic disturbances, whereas CCL2 and IL-1β may be more indicative of chronic adipose tissue inflammation.

Diagnostics doi: 10.3390/diagnostics16101458

Authors: Christina Pagkaki Panayiota Papasozomenou Efthymios Oikonomou Sofoklis Stavros Anastasios Potiris Nikoletta Koutlaki Menelaos Zafrakas Angeliki Gerede

Obstetric anal sphincter injuries (OASIs) are serious complications of vaginal delivery and the most frequent cause of postpartum anal incontinence. Underdiagnosis during delivery persists due to limited availability of accurate imaging. Transperineal ultrasound (TPUS) and endoanal ultrasound (EAUS) enable structural assessment of the anal sphincter and have growing roles in triage, repair planning, and follow-up.The aim of the present review is to integrate current evidence on diagnostic value, clinical usefulness, and potential implementation of TPUS and EAUS in gynecologic practice.Ultrasound identifies a high burden of occult sphincter trauma in primiparas with normal clinical assessment with rates close to 25%. EAUS is currently the gold standard for accurate imaging of defects. TPUS has excellent diagnostic performance for external anal sphincter (EAS) defects and is practical for bedside use. Improving the diagnosis of OASIs requires structured post-delivery clinical examination combined with selective use of TPUS as a first-line imaging modality and EAUS in cases of diagnostic uncertainty or suspected complex injury.Immediate postpartum ultrasound may help reduce delayed diagnoses and support timely surgical repair. Key barriers include operator dependence, training, availability, and variable image quality, particularly for routine EAUS in the labor ward.Incorporating ultrasound into postpartum management improves detection and classification of OASIs and subsequently repair and prognosis. Currently, judicious application in high-risk deliveries seems to be an appropriate approach until more evidence from prospective and economic studies is available. New technologies (3D/4D imaging, standardized terminology, and decision-support/AI) hold promise to increase reproducibility and use in everyday clinical practice.

Diagnostics doi: 10.3390/diagnostics16101457

Authors: Muzammil H. Syed Abdelrahman Zamzam Farah Shaikh Ori D. Rotstein David J. Klein Houssam Younes Rawand Abdin Mohammad Qadura

Background/Objective: Peripheral arterial disease (PAD) is a widespread but underdiagnosed manifestation of systemic atherosclerosis, associated with high morbidity and mortality. Traditional diagnostic methods such as the ankle-brachial index (ABI) have limited sensitivity in certain populations, highlighting the need for reliable blood-based biomarkers. Fatty Acid Binding Protein 3 (FABP3) has emerged as a robust biomarker with diagnostic utility in PAD. To evaluate the diagnostic performance of FABP3 when used in combination with traditional clinical risk factors for PAD in patients presenting to vascular surgery clinics. Methods: A retrospective analysis was conducted on 657 patients presenting to ambulatory vascular surgery clinics at St. Michael’s Hospital. Two logistic regression models were compared: (1) Model A: Included standard clinical risk factors (calf pain, age, smoking, diabetes, hypertension, hypercholesterolemia, coronary artery disease, and signs of chronic limb-threatening ischemia); and (2) Model B: Included the same factors as Model A, plus FABP3 levels. Diagnostic metrics including area under the curve (AUC), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy were assessed. Results: Among 657 patients, 423 had PAD and 234 did not. Model B (FABP3-integrated model) outperformed Model A, with a higher AUC (0.86 vs. 0.82), sensitivity (96% vs. 81%), specificity (84% vs. 67%), PPV (92% vs. 81%), NPV (94% vs. 65%), and diagnostic accuracy (93% vs. 76%). FABP3 also improved detection in asymptomatic PAD patients (84% detected vs. 0%). Conclusions: Integrating FABP3 with standard clinical risk factors significantly improves PAD diagnosis, especially in asymptomatic and borderline cases. These findings support the potential role of FABP3 in routine PAD screening, warranting further prospective studies for validation.

Diagnostics doi: 10.3390/diagnostics16101456

Authors: Qingyang Zhang Zeyu Deng Wenzhe Yan Hongkai Zhu Zizhu Tian Yi Jiang Hongling Peng

Objectives: Marginal zone lymphoma (MZL) is a heterogeneous indolent B-cell lymphoma, and current clinical prognostic systems remain limited in identifying transformation risk and refining risk stratification. This study aimed to evaluate the prognostic relevance of artificial intelligence (AI)-quantified immunohistochemical (IHC) markers in MZL and to explore a revised MZL-IPI model. Methods: We retrospectively analyzed 146 patients with pathologically confirmed MZL treated at the Second Xiangya Hospital of Central South University from January 2015 to June 2022. Among them, 111 patients had digitized IHC slides available for AI-assisted quantitative analysis. AI-quantified IHC marker expression was assessed in relation to clinical features, histologic transformation, and survival outcomes. Prognosis-related markers were dichotomized using optimal cut-off values. Survival differences were evaluated using the log-rank test, independent prognostic factors were identified by multivariable Cox regression, and model performance was assessed by cross-validation. Results: Age, B symptoms, hypertension, diabetes mellitus, and gastric involvement were associated with selected IHC parameters. CD3 was independently associated with histologic transformation, with expression below 25.60% indicating higher transformation risk. High CD21 expression independently predicted favorable overall survival (OS), whereas high CD3 expression was associated with inferior progression-free survival (PFS). Incorporating CD21 into the MZL International Prognostic Index (MZL-IPI) improved OS prediction in this cohort. Conclusions: AI-assisted quantitative IHC analysis may provide complementary prognostic information in MZL. The CD21-revised MZL-IPI represents an exploratory framework for integrating AI-derived tissue biomarkers with clinical risk stratification, but external multicenter validation is required before clinical application.

Diagnostics doi: 10.3390/diagnostics16101455

Authors: Tsubasa Hasegawa Yuki Okazaki Yusuke Mochizuki Takayuki Furumatsu Takaaki Hiranaka Koki Kawada Toshiki Kohara Tomonori Tetsunaga Toshifumi Ozaki

Background/Objectives: In periarticular knee surgery, such as osteotomies, ligament reconstruction, and fracture fixation, surgeons face a dilemma: ensuring the safety of the popliteal artery (PA) while securing adequate surgical access to the bone. While macroscopic anatomical studies suggest knee flexion protects the PA, they often fail to account for physiological muscle tension in living knees. This study aimed to quantitatively evaluate the dynamic positional changes in the PA and the vastus medialis and lateralis muscles (VM and VL, respectively) using Open Magnetic Resonance Imaging (MRI) to determine the optimal limb position for each surgical step. Methods: Twenty-three living knees were evaluated using Open MRI. The shortest perpendicular distances from the posterior aspect of the femur and tibia to the PA, and from the femoral cortex to the posterior border of the VM and VL, were measured at 10° knee-flexed position (representing the extended position) and 90° knee-flexed position. Results: The PA shifted significantly away from the bone in 90° knee-flexed position compared to extension at the distal femur (0 and 1 cm proximal to the intercondylar line (Blumensaat’s line)) and the proximal tibia (0, 1, and 2 cm distal to the joint line) (Q < 0.05). Conversely, both the VM and VL moved significantly closer to the femur in flexion at all measured levels (0–4 cm) (Q < 0.05), often causing the muscles to compress tightly against the bone. Conclusions: The vascular safety margin is maximized in flexion, whereas surgical exposure for the distal femur is optimized in extension due to vastus muscle relaxation. We suggest performing superficial exposure and femoral plate insertion in extension, and surgical maneuvers involving the posterior cortex in flexion to minimize neurovascular and soft tissue complications.

Diagnostics doi: 10.3390/diagnostics16101454

Authors: Vanessa Talavera-Cobo Jose Enrique Robles-Garcia Francisco Guillen-Grima Andres Calva-Lopez Mario Tapia-Tapia Luis Labairu-Huerta Francisco Javier Ancizu-Marckert Laura Guillen-Aguinaga Daniel Sanchez-Zalabardo Bernardino Miñana-Lopez

Background: An accurate D’Amico risk stratification is mandatory for prostate cancer (PCa) management. The purpose of this proof-of-concept study was to establish a methodological framework for integrating validated clinical nomograms with strict data-quality governance in order to generate reliable artificial neural networks (ANNs), even when the sample is small. Methods: We performed a retrospective analysis of a curated cohort of 49 patients from one centre. A multilayer perceptron (MLP) was trained using 11 variables, including the ISUP biopsy grade and Briganti nomogram. Model development was guided by a proactive data-quality protocol based on FAIR principles—the DQG-AI framework (data quality governance for AI-readiness, developed at Clínica Universidad de Navarra)—with stringent checks for accuracy, consistency and validity to ensure data were “AI-ready”. A sensitivity analysis was conducted on three data partitioning scenarios (20/80, 34/66 and 39/61). Results: From a starting pool of 76 patients, the DQG-AI framework was applied to create a highly selected cohort of 49 patients. A multilayer perceptron (MLP) trained on this “AI-ready” dataset achieved, on the 20/80 configuration, mathematically perfect discrimination (AUC 1.000; 100% accuracy) for High vs. Intermediate risk groups on a very small refined internal test set (N = 9), a figure we interpret as a methodological artefact of the curated dataset and validation constraints rather than as an indicator of true model performance. This complete accuracy is not, however, presented as evidence of generalizable clinical utility: it is a best-case figure obtained on a single, very small test subset (N = 9) after necessary validation-related exclusions, and the wide confidence interval (66.4–100%), together with the software-driven removal of test cases carrying factor levels absent from the training set (detailed in the Methods section), explicitly preclude any inference about real-world performance. Accordingly, the deliverable of this proof-of-concept study is the DQG-AI framework itself, not the model’s reported accuracy. Conclusions: The main contribution of this proof-of-concept study is the effective illustration of the DQG-AI framework as a strict, repeatable approach for producing “AI-ready” urological datasets. Although the MLP demonstrated a robust internal signal for risk discrimination, its flawless accuracy is an ideal, non-generalizable situation. The most important deliverable that needs external validation is the DQG-AI framework, not the model’s performance metrics. A pre-specified three-phase multi-institutional validation roadmap (single-centre cohort expansion → within-system between-site validation → Spanish multi-centre external validation), with a minimum target of ~220 evaluable patients derived from a 10-events-per-predictor floor, is provided to operationalise this external validation.

Diagnostics doi: 10.3390/diagnostics16101453

Authors: Nebiha Gozde Ispir Gokalp Aslan

Background: We evaluated whether mandibular trabecular microarchitecture, measured via fractal dimension (FD), influences Stafne bone cavity (SBC) development. Methods: In this study, 14 images (0.56%) containing SBC were identified among 2500 retrospectively reviewed cone-beam computed tomography (CBCT) images. Among the detected SBCs, those with panoramic radiographs in the archive were included in the study. Two groups were formed based on panoramic images: an SBC group and a control group consisting of individuals without SBC, with a similar sample size. FD analysis was performed using ImageJ version 1.3 software (National Institutes of Health, Bethesda, MD, USA) on the panoramic radiographs of these two groups. Post hoc power analysis and Cohen’s effect size were calculated to evaluate the robustness of the results. Results: No significant difference existed between the mean FDs of the SBC and control groups (p > 0.05). Mean FD values were slightly lower in SBC regions (1.18 ± 0.22), compared to other mandibular regions (~1.23–1.30). While FD averages were lower within SBC regions, effect size analysis showed negligible differences (d < 0.21) in posterior regions, indicating structural similarity. However, a large effect size (d = −0.85) in the canine–lateral region suggested a localized trend. Conclusions: Within the limitations of this pilot study, SBC does not appear to disrupt the surrounding trabecular structure of the mandible. The findings support the static and developmental nature of SBC.

Diagnostics doi: 10.3390/diagnostics16101452

Authors: Taimei Egashira Masayoshi Kobayashi Eisuke Ishigami

Background/Objectives: Seromucinous hamartoma (SH) is an extremely rare benign glandular lesion arising in the nasal cavity and paranasal sinuses, characterized by proliferation of serous and mucinous glands. Preoperative diagnosis by biopsy is extremely uncommon, making it a diagnostic challenge. We report a case of SH and discuss its diagnostic difficulties and management. Case Presentation: A 52-year-old man presented with right-sided nasal obstruction. A lobulated mass in the posterior right nasal cavity was incidentally detected during transnasal endoscopy. The lesion persisted for one year without reduction. CT, MRI, and biopsy failed to provide a definitive diagnosis. The patient was referred to our department, and endoscopic surgery under general anesthesia was performed. The tumor was removed en bloc. Histopathological examination revealed glandular proliferation of mixed serous and mucinous glands within the subepithelial stroma, consistent with SH. Discussion: Preoperative diagnosis is difficult due to insufficient biopsy depth and limited recognition of this rare entity. Since the surface epithelium shows no atypia, identification of subepithelial glandular proliferation is essential. Larger and deeper biopsy specimens and communication with pathologists may improve diagnostic yield. Surgical excision is the treatment of choice. As SH often arises in the posterior nasal cavity and is highly vascular, en bloc resection under general anesthesia is recommended. Conclusions: Recognition of SH is important to improve diagnostic accuracy. Appropriate biopsy strategy and surgical planning based on tumor location are essential.

Diagnostics doi: 10.3390/diagnostics16101451

Authors: Mengmeng Zhang Xinxin Mao Xi Wu Wen Shi Yunlu Feng Aiming Yang

The endoscopic findings of gastric mucosa-associated lymphoid tissue (MALT) lymphoma are highly nonspecific and the sampling error or false-negative probabilities during conventional biopsy make its diagnosis more challenging. Confocal laser endomicroscopy is a novel technology which allows in vivo microscopic analysis of gastrointestinal mucosa. Here we present a case of gastric MALT lymphoma by targeted biopsy guided by magnifying endoscopy and probe-based confocal laser endomicroscopy.

Diagnostics doi: 10.3390/diagnostics16101450

Authors: Bernat Rovira-Lastra Sanaa ElOtmani-Sabiri Mireia Ustrell-Barral Laura Khoury-Ribas Jordi Martinez-Gomis

Background/Objectives: This clinical study assessed the validity of articulating paper for detecting occlusal contacts points, including examining the effects of clinical technique, paper thickness, and the arch. Methods: This cross-sectional test–retest study included 32 adults with natural dentitions. Four occlusal registrations were obtained from each participant using articulating paper with a thickness of 100 or 200 μm, applying one of two different clinical techniques (holding in place or pulling with forceps at the intercuspal position), and scanning the occlusal surfaces of their mandibular and maxillary arches. Silicone registrations were obtained and used as the reference standard. Mandibular and maxillary images were scaled and calibrated spatially, and two new images were created based on the sum or the areas of coincidence between the mandibular and maxillary occlusal scheme. Occlusal contact points on the right posterior teeth were analyzed using computer software. Results: The articulating paper produced true-positive contacts in 81% and false-positive contacts in 15%, regardless of the method used. Considering occlusal contact when marks matched on both arches accounted for 2.0% of false-positive contact points. General linear models with repeated measures revealed that the mandibular arch offered a higher true-positive percentage than the maxillary arch, that the 100 µm-thick paper produced higher false-positive contacts (20.6%) than the 200 µm-thick paper (9.4%), and that the pulling technique had no significant effect. Conclusions: Articulating paper offers good validity when detecting occlusal contact points and can be improved by using 200 µm articulating paper and exploring both arches.

Diagnostics doi: 10.3390/diagnostics16101448

Authors: Stefano Palermi Rita Pucciatti Nor-Eddine Regnard Ali Guermazi Fabiano Araujo Andrea Demeco Yosra Mekki Giuseppe D’Antona Alessia Guarnera Simone Cerciello Matteo Guzzini Marco Vecchiato

Background: Artificial intelligence (AI) is rapidly transforming healthcare, with increasing applications in sports medicine. Advances in machine learning, deep learning, and computer vision enable the analysis of large, heterogeneous datasets derived from imaging, wearable sensors, performance-monitoring systems, and electronic health records. While these technologies offer opportunities to enhance injury prevention, diagnostic accuracy, rehabilitation monitoring, and clinical decision-making, their integration into athlete care remains complex and context-dependent. Methods: A structured narrative review of the PubMed/MEDLINE database was conducted to identify clinically relevant AI applications in sports medicine. The search focused on key domains including injury risk prediction, musculoskeletal imaging, rehabilitation monitoring, return-to-play assessment, performance management, and clinical workflow support. Evidence from original studies, reviews, methodological reports, and regulatory documents was qualitatively synthesized to provide an overview of current applications, methodological limitations, and decision-level implications. Results: AI demonstrates growing utility across multiple domains of sports medicine. Machine learning models can identify complex, non-linear relationships among training load, physiological responses, and injury risk, though their predictive performance varies widely and is often limited by dataset heterogeneity and a lack of external validation. In musculoskeletal imaging, AI-based algorithms support automated detection and quantification of abnormalities, with performance in selected tasks approaching that of expert readers, yet remaining task-specific and context-dependent. Emerging applications include movement analysis and rehabilitation monitoring through wearable sensors and computer vision systems, as well as data-driven support for return-to-play decisions and clinical workflow optimization. However, current evidence highlights important limitations, including algorithmic bias, limited generalizability, poor interpretability, and the risk of misapplication in complex clinical decision-making contexts. Conclusions: AI is likely to become an important decision-support layer in sports medicine by enabling data integration and longitudinal monitoring. However, model performance does not necessarily translate into improved clinical outcomes, and AI-generated predictions remain probabilistic and context-sensitive. Consequently, clinical decisions—particularly high-stakes processes such as return-to-play—require structured integration of AI outputs within a broader clinical framework. The sports physician remains central as a human-in-the-loop integrator, responsible for contextualizing AI-derived information, mitigating potential errors, and ensuring safe, individualized athlete management.

Diagnostics doi: 10.3390/diagnostics16101449

Authors: Mihnea-Ionuț Nicoară Mihai Adrian Socaciu Diana Ursu Andra Ciocan Nadim Al Hajjar

Background: Preoperative CT is part of the routine diagnostic work-up for colorectal cancer (CRC), and CT-based biomarkers have been linked to oncological and surgical outcomes in CRC patients. This review aims to evaluate the association between preoperative CT-derived vascular disease markers (calcification and stenosis) and postoperative outcomes after curative CRC resection with anastomosis. Methods: Following PRISMA, we conducted a systematic review and meta-analysis of studies identified from MEDLINE/PubMed, Embase, Web of Science Core Collection and Google Scholar from inception until 1st of January 2026, with the protocol registered in PROSPERO (CRD420251248044). Eligible studies examined CT-derived abdominal vascular disease markers in CRC patients treated with curative resection and anastomosis and reported postoperative outcomes (anastomotic leakage (AL) grade C, major morbidity, and mortality). Risk of bias was assessed using the Newcastle–Ottawa Scale. We pooled odds ratios using random-effects models when ≥3 studies reported comparable exposure–outcome comparisons. Results: Fourteen studies (6712 participants) were included, and 12 contributed to quantitative synthesis. Higher calcification burden was associated with increased odds of any AL (OR 3.08, 95% CI 2.09–4.54; k = 11; n = 5005) and severe/grade C AL (OR 2.68, 95% CI 1.03–6.97; k = 3; n = 3418). Evidence for major morbidity was imprecise (OR 1.99, 95% CI 0.86–4.59; k = 3; n = 841), and data for mesenteric stenosis outcomes and mortality were limited. Sensitivity analyses indicate attenuation without loss of significance after trim-and-fill (adjusted OR 2.39) and that non-ROC cut points yield a smaller effect size (OR 2.42). Conclusions: CT-derived vascular disease markers are associated with higher odds of AL after CRC surgery. Prospective studies should standardize methods and test clinical utility.

Diagnostics doi: 10.3390/diagnostics16101445

Authors: Brigitte Osser Csongor Toth Gyongyi Osser Laura Ioana Bondar Liliana-Oana Pobirci Florin Mihai Marcu Ramona Nicoleta Suciu Nicoleta Anamaria Pascalau Adina Mincic Corina Dalia Toderescu

Background/Objectives: Spinal alignment is a key determinant of biomechanical function and postural stability, particularly during periods of growth and development. Three-dimensional (3D) surface topography offers a non-invasive method for assessing spinal posture. This study aimed to evaluate spinal alignment parameters in a mixed adolescent and adult population, to investigate sex-related differences, and to analyze biomechanical relationships between spinal components. Methods: A total of 98 participants (aged 11–45 years) underwent 3D spinal surface topography assessment. Descriptive statistics were calculated for sagittal, coronal, and rotational parameters. Group comparisons between sexes were performed using independent samples t-tests. Pearson correlation analysis and linear regression were used to assess the relationships between spinal parameters. Logistic regression analysis was conducted to identify predictors of clinically relevant rotational asymmetry (surface rotation RMS > 6°). Results: Most participants exhibited near-physiological sagittal alignment, with thoracic kyphosis and lumbar lordosis within normal ranges. However, approximately 20% demonstrated clinically relevant rotational asymmetry. Female participants showed significantly higher rotational asymmetry compared to males (p = 0.008), while sagittal parameters did not differ significantly. Strong correlations were observed between thoracic kyphosis and cervical sagittal displacement (r = 0.77). Rotational asymmetry was negatively correlated with sagittal parameters and significantly predicted coronal imbalance (β = 0.38, p < 0.01; R2 = 0.21). Conclusions: 3D surface topography provides a non-invasive method for assessing external postural alignment and surface-based asymmetries. Rotational asymmetry appears to represent a relevant component of spinal imbalance and is associated with coronal deviation within a multi-planar framework. These findings support the use of integrated biomechanical assessment in the evaluation of spinal alignment.

Diagnostics doi: 10.3390/diagnostics16101447

Authors: Christina H. Wolfsberger Christoph Schlatzer Ena Suppan Marlies Bruckner Nina Hoeller Bernhard Schwaberger Gerhard Pichler

Background/Objectives: Peripheral(-muscle) oxygenation assessed with near-infrared spectroscopy might serve as an early marker of infection/inflammation; however, evidence of its clinical relevance is lacking so far. This study aimed to develop a peripheral(-muscle) oxygenation and perfusion score (POP-Score) using the peripheral(-muscle) tissue oxygenation index (pTOI) combined with non-invasive monitoring parameters within six hours after birth. The POP-Score was designed to explore associations with elevated C-reactive protein (CRP), as an early infection/inflammation marker, in term and late-preterm neonates. Methods: Secondary outcome parameters from a prospective observational study were analysed. Included neonates weighed ≥2000 g with respiratory distress, excluding those with umbilical artery pH < 7.20. Neonates with CRP ≥ 20 mg/L were 1:4-matched to those with CRP < 20 mg/L by gestational age (±2 weeks). For pTOI measurements, a sensor was placed for a duration of 30 s, followed by four further reapplications of the sensor, using the NIRO200NX within the first six hours after birth. The POP-Score was established using the following formula: (pTOI [%] × subcutaneous fat layer thickness [cm] × heart rate [bpm])/(arterial oxygen saturation [%] × systolic blood pressure [mmHg]). POP-Score was correlated with the highest CRP within 48 h. Results: Thirty neonates were included (median gestational age: 39.1 weeks [CRP < 20 mg/L group] vs. 37.3 weeks [CRP ≥ 20 mg/L group], p = 0.299; median birth weight: 3561 g vs. 3260 g, p = 0.058, respectively). Median POP-Scores were significantly different: 1.11 (CRP ≥ 20 mg/L) vs. 0.85 (CRP < 20 mg/L), p < 0.001. POP-Score correlated positively with CRP (r = 0.341; p = 0.070). In this small exploratory cohort, a POP-Score cut-off of 1.00 was associated with CRP ≥ 20 mg/L (100% sensitivity and 87% specificity); however, these estimates are uncertain due to the limited sample size. Conclusions: This study is the first to describe a new score for peripheral(-muscle) oxygenation and perfusion (POP-Score), which may represent a potential approach for early, non-invasive assessment but requires validation in adequately powered studies before any clinical application. Trial Registration: Clinicaltrials.gov, Trial registration number: NCT04818762, Date of Registration: 26 March 2021

Diagnostics doi: 10.3390/diagnostics16101446

Authors: Elena Grueso-Navarro Victoria Úbeda-Vargas Rocío Juárez-Tosina Laura Arias-González Emilio J. Laserna-Mendieta Alfredo J. Lucendo

Background/Objectives: The recommendation of routine gastric and duodenal biopsies at index endoscopy on suspicion of eosinophilic esophagitis (EoE) remains controversial because of the limited supporting evidence. We aimed to evaluate the prevalence, clinical relevance, and predictors of gastric and duodenal histopathology in a large real-world EoE cohort. Methods: This retrospective single-center study included adult and pediatric patients with EoE diagnosed between 2001 and 2024 and enrolled in the EoE CONNECT registry. Gastric and/or duodenal biopsies obtained at diagnosis or follow-up were reviewed. Histologic findings were classified into specific diagnostic categories and analyzed according to clinical presentation, endoscopic features, and age group. Results: We evaluated 340 patients (35.7% children), of whom 88.5% underwent both gastric and duodenal biopsies. The overall diagnostic yield for extra-esophageal findings was 20.9%, predominantly Helicobacter pylori-associated gastritis (18.8%), but with a very low yield of clinically meaningful diagnoses such as celiac disease (0.6%) and eosinophilic gastritis (0.3%). Symptoms and endoscopic abnormalities were not significantly associated with pathological findings (p=0.11). Moreover, age-stratified analysis revealed no significant differences in specific diagnoses, although patients with pathological extra-esophageal biopsies were significantly older (p<0.001). Follow-up biopsies demonstrated resolution of most pathological findings after the initial diagnosis, with Helicobacter pylori-associated gastritis accounting for the majority of cases that resolved. Conclusions: Routine extra-esophageal biopsies in the context of patients with EoE have a low diagnostic yield and rarely alter clinical management, regardless of age. Therefore, our findings advocate for a selective rather than universal approach to extra-esophageal sampling in patients with EoE.

Diagnostics doi: 10.3390/diagnostics16101444

Authors: Helal F. Hetta Rehab Ahmed Abdul Haseeb Salwa Qasim Bukhari Zinab Alatawi Ahmad J. Mahrous Mahmoud E. Elrggal Ali M. Atoom Yasmin N. Ramadan Ahmed A. Kotb

Human metapneumovirus or HMPV is an important respiratory pathogen of public health significance that primarily affects the immunocompromised, the very old, and young infants. However, recent studies have long since dispelled the idea that healthy adults are not at risk for serious sequelae, though it seems that HMPV has a particular affinity to infect children rather than adults. HMPV was first identified in 2001 and is implicated in a range of respiratory illnesses, from less severe upper respiratory infections to more severe pneumonia. This review compiles the recent literature on the epidemiology, molecular virology, and clinical characteristics of HMPV with an emphasis on, importantly, the virus’s significant contribution to respiratory morbidity and the requirement for better diagnostic capabilities and public health measures against this very much underappreciated viral pathogen.

Diagnostics doi: 10.3390/diagnostics16101443

Authors: Haruo Miwa Kuniyasu Irie Tomoko Fujiyoshi Nene Sakai Ryo Soma Kozue Shibasaki Yugo Ishino Shotaro Tsunoda Yuto Matsuoka Tomomi Hamaguchi Kazuki Endo Ritsuko Oishi Yuichi Suzuki Hiromi Tsuchiya Akihiro Funaoka Yoshimasa Suzuki Satoshi Komiyama Yoshihiro Goda Manabu Morimoto Shin Maeda

Background/Objectives: The role of peroral pancreatoscopy (POPS) in patients with main-duct and mixed-type intraductal papillary mucinous neoplasm (MD/mixed-IPMN) remains unclear. This retrospective multicenter case series aimed to evaluate the feasibility and safety of POPS using the 9-Fr eyeMAX and to describe additional intraductal findings, potential surgical impact, and biopsy–surgery concordance. Methods: Consecutive patients with MD/mixed-IPMN in whom POPS was attempted between May 2023 and September 2025 were retrospectively analyzed. Pre-POPS imaging findings, POPS findings, procedural outcomes, adverse events, surgical outcomes, and concordance between POPS-guided biopsy and surgical pathology were evaluated. Results: Among the 20 patients, 14 were men, and the median age was 74.5 years (range, 46–83 years). IPMNs were classified as main-duct type in five patients (25%) and mixed type in 15 (75%). On endoscopic ultrasonography, mural nodules were identified in 14 patients (70%), with a median diameter of 11 mm (range, 3–25 mm). Endoscopic papillary intervention was performed in 6 patients (30%). The technical success rate of POPS insertion was 95% (19/20). Mural nodules were detected by POPS in 17 patients (85%), and biopsy under POPS guidance was performed a median of 5 times (range, 1–10). The adequate tissue sampling rate was 86% (88/102). Mild post-ERCP pancreatitis occurred in 1 patient (5%). Twelve patients (60%) underwent surgery. The concordance rate between POPS-targeted biopsy and surgical pathology was 45% (5/11); however, R0 resection was achieved in 11 patients (92%). Conclusions: In this small retrospective case series, POPS using the 9-Fr eyeMAX was feasible and provided additional intraductal information in selected patients. However, its diagnostic role remains adjunctive because POPS-guided biopsy showed limited reliability.

Diagnostics doi: 10.3390/diagnostics16101442

Authors: Yi-Chi Hung Yun-Ju Wu Fu-Zong Wu

Lung cancer screening has been widely studied, and strong evidence supports its role in reducing mortality among heavy smokers. The 2011 National Lung Screening Trial demonstrated a 20% reduction in lung cancer mortality, with further validation from European trials, such as NELSON and MILD. In 2015, the United States Centers for Medicare & Medicaid Services approved lung cancer screening as a reimbursable service, later expanding the criteria in 2021 to include individuals aged 50–80 years with a ≥20 pack-year smoking history. While screening models such as the Prostate, Lung, Colorectal, and Ovarian (PLCO) have effectively stratified risk among smokers, emerging research on non-smokers remains inconclusive. This review highlights five key issues in lung cancer screening in Eastern and Western countries. First, the screening rates differ significantly between regions owing to variations in healthcare policies and awareness. Second, subsolid nodule (SSN) prevalence varies between Eastern and Western populations, influencing screening strategies. Third, differences in SSN growth thresholds affect clinical decision-making and patient outcomes. Fourth, there are variations in the management of SSNs, particularly in follow-up recommendations and intervention strategies. Fifth, overdiagnosis remains a critical concern, with distinct challenges in each region owing to screening frequency and healthcare infrastructure. Additionally, microsimulation models predict a decline in smoking-related lung cancer but an increase in non-smoking-related cases, emphasizing the need for tailored screening approaches. Addressing these five issues is crucial for optimizing lung cancer screening strategies and balancing early detection with the risk of overdiagnosis.

Diagnostics doi: 10.3390/diagnostics16101441

Authors: Yi Luo Yike Guo Hamed Hooshangnejad Xue Feng Quan Chen Zongwei Zhou Yaxi Chen Yipeng Hu Rui Zhang Kai Ding

Background/Objectives: Accurate detection of pulmonary nodules on chest CT is critical for lung cancer screening, yet training robust detectors remains challenging due to the high cost of reliable annotations. In this work, we present a systematic study of curriculum learning for CT-based lung nodule detection on the enhanced LUNA25 benchmark and propose a hybrid curriculum learning framework for data-efficient optimization. Methods: Our approach estimates sample difficulty by fusing clinically interpretable handcrafted factors such as nodule size and count with model-driven signals such as prediction confidence from a teacher model, and constructs a three-stage progressive training curriculum from easy to hard samples. Using YOLOv11s as a strong baseline, the proposed hybrid curriculum is compared against conventional training without curriculum learning and against single-source curricula. Results: On the held-out LUNA25 test set, hybrid curriculum learning increases mAP50 from 0.672 to 0.696, mAP50–95 from 0.369 to 0.385, recall from 0.588 to 0.634, and precision from 0.725 to 0.764. Extensive data-efficiency experiments with proportional reductions (1/2, 1/5, 1/10) and fixed training samples (5000–40,000 slices) further confirm consistent gains across limited-data regimes. Conclusions: These results demonstrate that jointly leveraging intrinsic image complexity and optimization-aware feedback provides effective sample scheduling for robust and data-efficient lung nodule detection.

Diagnostics doi: 10.3390/diagnostics16101440

Authors: Isaac Zablah Yolly Molina Edil Argueta Marcio Madrid

Background/Objectives: Frailty is common in Latin America and the Caribbean, yet validated, low-cost screening tools based only on routine clinical data remain limited. We developed benchmarked interpretable machine learning models for frailty screening in older adults and assessed the added value of SARC-F beyond basic hemodynamic and anthropometric measures. Methods: In this cross-sectional pilot diagnostic modeling study, 100 older adults (mean age 69.8 ± 6.8 years; 73% women) from a tertiary care center were classified with the FRAIL scale. The primary endpoint was frail versus non-frail. Three logistic regression models were evaluated using stratified 5-fold cross-validation: Model A (age, sex, BMI, nutritional status, systolic and diastolic blood pressure), Model B (mean arterial pressure and pulse pressure), and Model C (Model A plus SARC-F). Decision tree and random forest were secondary comparators. Results: SARC-F was the only variable significantly associated with frailty category (p < 0.001). Models A and B showed near-chance discrimination (both AUC = 0.546), whereas Model C achieved an AUC of 0.921 (95% CI: 0.864–0.966), sensitivity of 0.812, specificity of 0.846, and F1-score of 0.821. SARC-F alone yielded an AUC of 0.942. In Model C, SARC-F was the dominant predictor (standardized OR 12.52, 95% CI: 8.90–23.91). Conclusions: Routine hemodynamic and anthropometric variables alone were inadequate for frailty discrimination. SARC-F captured most of the discriminative signal, supporting its use for frailty screening in resource-limited geriatric settings. Although the logistic regression pipeline was transparent and computationally inexpensive, external prospective validation is required.

Diagnostics doi: 10.3390/diagnostics16101439

Authors: Mehmet Yiğit Gökmen Mehmet Maden Onur Zengin

Background: Large language models (LLMs) are increasingly used for musculoskeletal health information, yet their safety in time-sensitive shoulder and elbow presentations with red-flag features remains insufficiently defined. We evaluated safety behavior using standardized vignettes, focusing on safety-critical under-triage and prompt-dependent performance differences. Methods: Eighty fictional vignettes (40 shoulder, 40 elbow) were created and classified a priori as red-flag (n = 24) or non-urgent (n = 56). Each vignette was queried in a single-turn format using three fixed prompt types (patient-, general physician-, and specialist-oriented), yielding 240 responses. Two blinded orthopedic surgeons rated outputs using a prespecified 0–8 rubric across four domains. Safety-critical under-triage was defined as failure to recommend timely urgent evaluation in red-flag presentations. Decision stability was assessed using 20 paired vignette sets differing by one predefined clinical variable. Results: The overall mean score was 6.42 ± 1.12 and was lower for red-flag than for non-urgent responses (5.28 ± 1.21 vs. 6.93 ± 0.81). Across the 72 prompt-specific responses generated for the 24 red-flag vignettes, urgency was correctly recognized in 53 responses (73.6%). Safety-critical under-triage occurred in 19 of 72 red-flag responses (26.4%) and was most frequent with patient-oriented prompts (10/24, 41.7%), followed by general physician-oriented prompts (6/24, 25.0%) and specialist-oriented prompts (3/24, 12.5%). Decision instability, defined as an inconsistent directional change after modification of a single risk-related variable, occurred in 6 of 20 paired vignette sets (30.0%). Conclusions: The evaluated LLM performed consistently well in non-urgent scenarios but showed prompt-dependent safety vulnerabilities in red-flag conditions, driven primarily by under-recognition of urgency. These findings support caution for unsupervised patient-facing use, highlight the need for explicit safeguards in high-risk presentations, and underscore the value of safety-focused evaluation frameworks in musculoskeletal care.

Diagnostics doi: 10.3390/diagnostics16101438

Authors: Bowen Su Yanpeng Zhang Xian Wu Yaping Jiang Yinan Song Xiaomin Shi

Background: The accuracy of tumor marker testing is critical for clinical decision-making. Patient-based real-time quality control (PBRTQC), as a complementary approach to traditional internal quality control (IQC), has been widely adopted in clinical laboratories. With the rapid advancement of automation and artificial intelligence (AI) in recent years, a large number of AI-based PBRTQC optimization algorithms have emerged. This study compared Patient-based real-time quality control integrating neural networks and joint probability analysis (NN-PBRTQC), Patient-Based Pre-Classified Real-Time Quality Control (PCRTQC), and traditional PBRTQC to identify the optimal method for quality control of tumor marker testing. Methods: The study utilized clinical tumor marker testing data from Peking University First Hospital. Six common tumor markers were selected, and constant error (CE) and proportional error (PE) were introduced as measures of analytical error. The False Alarm Rate (FAR) was used to reflect the specificity of the algorithms, while the Trimmed Average Number of Patient Results Affected Before Error Detection (tANPed) was used to reflect their sensitivity, in order to compare the clinical performance of the different models. Results: Under the same desired FAR (DFAR) of 0.1%, NN-PBRTQC reduced the tANPed for the six tumor markers by an average of 62% compared to the traditional PBRTQC while maintaining the same FAR, which demonstrated superior sensitivity of error detection. Meanwhile, although PCRTQC strictly controlled the FAR, its tANPed was 23% higher on average than that of the traditional PBRTQC, which indicated insufficient sensitivity of error detection. Conclusions: NN-PBRTQC demonstrated superior comprehensive quality control performance in the comparison of six common tumor markers. While ensuring that the FAR does not deviate from the DFAR, it significantly reduces tANPed, such that it could meet the specificity and sensitivity requirements of clinical testing. It is expected to enable more efficient and accurate detection of tumor marker errors.

Diagnostics doi: 10.3390/diagnostics16101437

Authors: Çağlar Uzun Sena Ünal Ebru Düşünceli Atman Elif Peker Ayşegül Gürsoy Çoruh Namik Kemal Altinbas Ayten Kayi Cangir

Thoracic outlet syndrome (TOS) is a rare neurovascular compression disorder involving the brachial plexus and/or subclavian vessels at the cervicothoracobrachial junction. Clinical presentation is often nonspecific and may overlap with peripheral neuropathies, cervical spine disorders, and musculoskeletal conditions, making diagnosis challenging. Although clinical evaluation remains central to diagnosis, imaging plays a complementary role in supporting the diagnosis of TOS by identifying the affected neurovascular structures, localizing the site of compression, and elucidating the underlying anatomical or pathological causes. Moreover, imaging is essential for excluding alternative diagnoses, including thoracic malignancies and inflammatory or degenerative vascular diseases that may mimic TOS. This review provides a comprehensive overview of the radiological anatomy of the thoracic outlet, the etiological factors contributing to neurovascular compression, and the strengths and limitations of current imaging modalities used in the evaluation of TOS.

Diagnostics doi: 10.3390/diagnostics16101436

Authors: Esra Yılmaz Hülya Kılıç

Background: Reference intervals for 25-hydroxyvitamin D are significantly influenced by seasonal variations and population-specific factors. This study aimed to establish local, population-specific Vitamin D reference intervals using the refineR algorithm and to compare these results with the conventional non-parametric method using a hospital database. Methods: A total of 127,220 laboratory results from 2022 to 2025 were retrospectively analyzed. Data were filtered based on adult age, morning fasting specimens, outpatient status, and normal parathyroid hormone levels (14–72 ng/L). Following filtration, Wilcoxon and Kruskal–Wallis tests were employed to evaluate differences between potential subgroups. Consequently, 24,036 eligible results were stratified by age (18–40, 41–65, and >65 years) and sex (female and male). Reference intervals were calculated using the refineR algorithm and the non-parametric percentile method. Results: The distribution of vitamin D levels was found to be right-skewed [Median: 12.92 ng/mL (4.21–149)]. The upper reference limits obtained via refineR were consistently lower than those derived from the non-parametric method. Both methods showed a linear increase in median values and upper reference limits with advancing age. Females in the 18–40 age group exhibited the lowest vitamin D profile. The summer concentrations were significantly higher than those of other seasons (p <0.05). Conclusions: The refineR algorithm managed outliers and pathological results more effectively than the non-parametric method. Our findings highlight the clinical necessity for age- and sex-specific subgroups, rather than relying on the manufacturer’s single reference range. Implementing these population-specific intervals can enhance diagnostic accuracy and prevent misclassification, facilitating earlier identification of vitamin D-related metabolic and skeletal disorders.

Diagnostics doi: 10.3390/diagnostics16101435

Authors: Rikke Baarts Alexander Cuculiza Henriksen Nathalie Sarup Panduro Emma Kanchana Ertner Bengtsson Ali Salari Caroline Clausen Lisbet Rosenkrantz Hölmich Lars Lönn Charlotte Mehlin Sørensen Jørgen Arendt Jensen Michael Bachmann Nielsen

Objectives: To systematically map the existing literature on ultrasound-based techniques for non-invasive visualization of the dermal microvasculature and identify methodological strengths, limitations, and evidence gaps. Methods: This scoping review was conducted according to PRISMA-ScR guidelines and registered on the Open Science Framework (DOI: 10.17605/OSF.IO/7VDUK). MEDLINE, PubMed, Embase, Scopus, and Web of Science were searched (January 2000–October 2025). Studies involving human participants and ultrasound-based techniques explicitly aimed at visualizing dermal microvasculature were included. Data on study design, population characteristics, imaging parameters, and reported outcomes were extracted and synthesized narratively. Results: Thirty-six studies published between 2007 and 2025 were included. Most were small feasibility or experimental studies (n = 24), with a median sample size of three participants and substantial heterogeneity in imaging protocols. Photoacoustic-based techniques were most frequently reported (n = 21) and were the most consistently described as providing high microvascular detail and functional assessment capability. High-frequency ultrasound (n = 10) and advanced Doppler methods (n = 7) also enabled visualization of dermal vessels, but showed variability in sensitivity, reporting, and standardization. Validation against histopathology was reported in only one study. Conclusions: Ultrasound-based techniques can visualize dermal microvasculature in vivo; however, evidence remains fragmented, methodologically heterogeneous, and largely derived from small exploratory studies. Standardized imaging protocols, pathology-based clinical cohorts and robust validation studies are required to establish comparative performance and enable clinical translation in radiology.

Diagnostics doi: 10.3390/diagnostics16101434

Authors: Paweł Gać Natalia Kusyn Rafał Poręba

Giant coronary artery aneurysms, defined as those with a diameter exceeding 8 mm or a four-fold increase relative to the reference vessel segment, are incredibly rare, with an estimated prevalence of approximately 0.02% in the general population. We present computed tomography angiography images of a thrombotic occlusion of a giant right coronary artery (RCA) aneurysm. An 80-year-old Caucasian man with chronic coronary artery disease, who had undergone percutaneous coronary intervention of the middle segment of the left circumflex artery (LCx) with drug-eluting stent implantation, was referred to the computed tomography department for coronary computed tomography angiography (CCTA) due to difficulty visualizing RCA during invasive coronary angiography. In CCTA, a giant aneurysm in the proximal segment of the RCA, with a massive thrombus, communicating with the typical origin of the RCA from the right aortic bulb sinus, then extending into the occluded part of the proximal segment of the RCA, was visualised. The maximum long dimension of the RCA aneurysm was 5.3 cm, and the maximum short dimension of the RCA aneurysm was 4.4 cm. The maximum thrombus thickness in the RCA aneurysm was 2.2 cm. The middle and distal segments of the RCA, presumably filled with collateral circulation, have significantly weaker contrast, and contain numerous predominantly calcified atherosclerotic plaques. In summary, the presented CCTA images confirm the clinical importance of this modality in diagnosing coronary artery aneurysms, even in situations where the results of invasive coronary angiography remain equivocal. Due to higher spatial resolution, the ability to perform image reconstruction in multiple planes, the ability to detect thrombus, and the ability to assess the vessel wall and extracoronary structures, CCTA not only enables the detection of coronary artery aneurysms but also enables risk prediction, thus enabling the planning of a more optimal treatment strategy.

Diagnostics doi: 10.3390/diagnostics16101432

Authors: Mikayla J. Foley Michael Cole Carolina Sandoval-Garcia Robert T. Galvin William B. Dobyns Collin M. McClelland Can Özütemiz

Background and Clinical Significance: CTC1-related cerebroretinal microangiopathy with calcifications and cysts (CRMCC), or Coats-plus syndrome, is an extremely rare autosomal recessive telomere-dysfunction disorder. A total of 29 cases in 15 reports have been reported in the English literature. The primary imaging characteristics include leukoencephalopathy, intracranial calcifications, and parenchymal cysts. Case Presentation: We describe a patient with CRMCC, who presented with a large intracranial cystic mass and basal ganglia calcifications, with imaging findings strongly mimicking a primary CNS tumor. The patient underwent multiple surgeries with inconclusive biopsies. Ultimately, it took five years and the collaboration of several specialists to arrive at the final diagnosis. Furthermore, we present dedicated clinical 7T orbit MRI findings on the patient’s brother, who has the same disease. Conclusions: We present a rare case of CRMCC with lack of overt leukoencephalopathy at presentation and absence of characteristic extracranial/extraocular manifestations, significantly complicating diagnosis. Furthermore, to the best of our knowledge, we share the first reported clinical 7T orbital MRI in the pediatric population.

Diagnostics doi: 10.3390/diagnostics16101433

Authors: Anikó Folhoffer Boglárka Zsély Anna Krolopp Dániel Németh Tamás Tóth Csaba Lőrinczi Krisztina Hagymási Anna Egresi Csenge Bánhidi Judit Halász Barbara Csongrády Bettina Katalin Budai Róbert Stollmayer Zsuzsanna Jakab András Laki Gabriella Győri Aladár Dávid Rónaszéki Pál Maurovich-Horvát Ferenc Szalay Pál Novák Kaposi István Takács

Background: Wilson’s disease (WD) is a genetic disorder of copper metabolism with over 600 disease-causing mutations, leading to variable hepatic and neurological symptoms. Early diagnosis and treatment are crucial. To evaluate hepatic involvement, serum scores and non-invasive imaging techniques complement histology. Methods: This pilot study assessed the utility of ultrasound-based tissue attenuation imaging (TAI), tissue scatter distribution imaging (TSI), and shear-wave elastography (SWE) for quantifying steatosis and fibrosis in WD. Results: Among 131 treated patients, 53 (mean age 40.5 ± 13.1 years, M/F = 35/18) underwent measurements. Based on literature-validated thresholds, 41 patients did not have significant liver fibrosis, 5 patients had moderate (F2) and 4 advanced (F3) fibrosis, while 3 patients had cirrhosis. The LS (liver stiffness) was in moderate correlation with FIB-4 (r = 0.306, p < 0.03), NAFLD fibrosis index (r = 0.336, p < 0.02), and APRI (r = 0.31, p = 0.0857). Among the WD patients, 37 had no steatosis (S0), 14 had mild steatosis (S1), and 2 had intermediate steatosis (S2); none of them had severe steatosis (S3) based on UEFF calculation. LS correlated positively with calculated free copper and negatively with serum ceruloplasmin. Normal-BMI patients exhibited no significant steatosis (R2 = 0. 0065, p = 0.966) by ultrasound-estimated fat fraction (UEFF), while those with BMI > 25 kg/m2 had increased UEFF correlating with BMI (R2 = 0.288, p < 0.015). Over a five-year follow-up using liver elastography, the fibrosis score did not progress significantly in adequately treated patients. Conclusions: Ultrasound with artificial intelligence-derived parameters supports the non-invasive evaluation of hepatic steatosis and fibrosis in WD, complementing clinical and laboratory data. However, population-specific liver stiffness thresholds are still needed.

Diagnostics doi: 10.3390/diagnostics16101430

Authors: Raúl Santiago-Montero Valentin Calzada-Ledesma David Asael Gutiérrez-Hernández Lucero de Montserrat Ortiz-Aguilar Armando Mares-Castro Luis Angel Xoca-Orozco José de Jesús Flores-Sierra

Background: Melanoma is one of the most aggressive forms of skin cancer, making early and accurate diagnosis essential for improving patient outcomes. Methods: In this work, we propose an Evolutionary Gabor-based Melanoma Descriptor (Evo-GMD), a lightweight and interpretable approach designed under the principles of Frugal AI. The method integrates multi-scale Gabor filtering with Differential Evolution to automatically learn discriminative texture patterns using a reduced set of parameters. The proposed approach was evaluated on the PH2 dataset, achieving competitive performance (accuracy above 95%) while maintaining low computational complexity and full interpretability. To further assess its robustness, complementary experiments were conducted on the ISIC 2017 dataset, which presents higher variability, class imbalance, and heterogeneous lesion characteristics. Results: The results reveal that multiple methods—including handcrafted descriptors, convolutional neural networks, and transfer learning models—exhibit significant performance degradation or converge to trivial solutions under these conditions. This behavior highlights that increasing model complexity does not necessarily improve classification performance when data constraints are present. Conclusions: Overall, the findings demonstrate that the proposed method provides a robust and efficient alternative for melanoma classification in low-resource scenarios, where data availability, computational capacity, and interpretability are critical factors.

Diagnostics doi: 10.3390/diagnostics16101431

Authors: Mihaela-Iuliana Sirbu Flavia Zara Raluca Maria Closca Marina Rakitovan Antonia Armega-Anghelescu Alexandru Cristian Cindrea Ovidiu-Alexandru Mederle Marcela-Maria Labadi Nicolae-Constantin Balica

Background/Objectives: Laryngeal squamous cell carcinoma exhibits marked heterogeneity in clinical behavior, which cannot be fully explained by conventional histopathological parameters alone. Increasing evidence highlights the pivotal role of the tumor immune microenvironment in modulating tumor progression and patient prognosis. Methods: The study group had 82 patients with laryngeal squamous cell carcinoma. A panel of immunohistochemical markers was chosen to identify and quantify key immune cell populations and immune-related components within the tumor immune microenvironment. Semiquantitative evaluation of immune infiltrates was conducted, with particular emphasis on their density and relative distribution across intratumoral and stromal compartments. Results: Based on the resulting immunophenotypic profiles, cases were categorized into three distinct immune patterns: an active immune type, defined by a prominent and dense inflammatory infiltrate; a mixed type, exhibiting intermediate and heterogeneous immune characteristics; and an immunosuppressive type, characterized by reduced effector immune cell infiltration and a predominance of immunoregulatory elements. Statistical analysis demonstrated significant correlations between these immune patterns and patient survival outcomes. Conclusions: The present study aimed to characterize the immune landscape of laryngeal squamous cell carcinoma using immunohistochemical markers and to evaluate its prognostic significance.

Diagnostics doi: 10.3390/diagnostics16101429

Authors: Pin-Chieh Wu Yun-Ju Wu Chiao-Lin Hsu Hsien-Chung Yu Chi-Shen Chen Fu-Zong Wu

Background: Low-dose computed tomography (LDCT) offers a unique opportunity to assess osteoporosis risk during routine lung cancer screening. This study aims to develop an integrated prediction model using trabecular bone features from LDCT and clinical factors to identify high-risk individuals early. Methods: This retrospective observational cohort study included 429 adults who underwent both DEXA and LDCT scans within one week at Kaohsiung Veterans General Hospital (2018–2022). Clinical data, including demographics, lifestyle factors, and comorbidities, were extracted from electronic records. Participants were categorized into osteoporotic (T-score ≤ −2.5) and non-osteoporotic groups. Trabecular bone morphometry was assessed at the T12 vertebra using QUIBIM Precision® software, analyzing parameters such as BV/TV, Tb.Th, Tb.N, Tb.Sp, D2D, D3D, and QTS. ROI placement and measurements followed standardized protocols. Ethical approval was obtained, and informed consent was waived. Statistical analyses included t-tests, ROC curves, logistic regression, and Delong tests to compare clinical and trabecular predictors of osteoporosis using SPSS v22. Results: In this study of 429 individuals, osteoporosis was significantly associated with female gender, older age, lower BMI, and smaller waist circumference. Trabecular bone morphometry revealed that osteoporotic individuals had significantly thinner trabeculae (lower Tb.Th), higher trabecular number (Tb.N), and more complex trabecular architecture (higher D2D/D3D), with lower QTS. Logistic regression showed that Model 1—the model combining clinical factors and Tb.N—showed a slightly higher predictive performance (AUC 0.738) than Model 2 (AUC 0.711), although the improvement was modest (p = 0.022). A nomogram based on age, sex, BMI, waist circumference, and Tb.N effectively estimated osteoporosis probability, providing a clinically useful tool for risk stratification. Conclusions: In conclusion, combining trabecular bone morphometry (Tb.N) from routine LDCT with age, sex, BMI, and waist circumference enhances osteoporosis risk prediction, enabling personalized assessment without extra radiation during standard lung cancer screening.

Diagnostics doi: 10.3390/diagnostics16101428

Authors: Bilgün Çetin Derya İçöz Kevser Dinç İsmail Kayadibi

Background/Objectives: This study aims to evaluate the diagnostic performance of radiomic features derived from cone-beam computed tomography (CBCT) images in differentiating radicular cysts (RC) from periapical granulomas (PG). The study also compares the performance of traditional machine learning (ML) algorithms with a novel deep learning (DL) model, Radiomics Cyst Convolutional Neural Network (RadC-CNN). Methods: CBCT images of 98 patients (55 RC, 43 PG), confirmed by histopathological diagnosis, were retrospectively analyzed. Lesions were semi-automatically segmented in 3D Slicer, and 48 radiomic features were extracted. Features with high inter-observer agreement (Intraclass Correlation Coefficient ICC ≥ 0.80) were included in the analysis. Statistical tests and classification models (Decision Tree, K-Nearest Neighbors, Support Vector Machine) were used, and performance was compared to that of the proposed RadC-CNN architecture. Results: Among the 34 features with sufficient reliability, 18 showed statistically significant differences between RC and PG (p < 0.05). Shape, first-order, and texture-based features, including the Gray Level Co-occurrence Matrix (GLCM), Gray Level Run Length Matrix (GLRLM), Gray Level Size Zone Matrix (GLSZM), and Neighboring Gray Tone Difference Matrix (NGTDM), were extracted. The RadC-CNN model demonstrated superior classification performance with an accuracy of 90%, sensitivity of 90%, and precision of 91.3%, outperforming all traditional ML algorithms. Conclusions: CBCT-based radiomic analysis, particularly when combined with DL techniques like RadC-CNN, offers a promising non-invasive approach to distinguish RC from PG.

Diagnostics doi: 10.3390/diagnostics16101427

Authors: Kamil Nelke Ömer Uranbey Ece Gülbağ Büşra Ekinci Burcu Gürsoytrak Angela Rosa Caso Michał Gontarz Maciej Janeczek Piotr Kuropka Maciej Dobrzyński

The range of possible inflammatory changes in the oral cavity and in the maxillary and mandibular bones may present with diverse patterns and characteristics in both clinical and radiological evaluation. In most cases, a standard radiological examination, such as dental panoramic radiograph (DPR), has significant limitations in assessing early or complex bone changes associated with chronic bone inflammation. Advanced imaging with multidetector computed tomography or cone-beam computed tomography (MDCT or CBCT) can improve lesion characterization and surgical planning when a detailed evaluation of tooth-bearing structures, tooth apices, cortical plates, and cancellous bone is required. Such imaging allows more detailed assessment of alterations in medullary bone morphology and architecture, as well as identification of possible periosteal reactions adjacent to chronic bone inflammation. Osteomyelitis of the jaws comprises a heterogeneous group of inflammatory bone disorders characterized by variable clinical presentations and a broad spectrum of radiological appearances. Depending on disease chronicity, host factors, and microbial burden, mandibular osteomyelitis may mimic odontogenic tumors, fibro-osseous lesions, or malignant bone pathologies. Quite often, dental treatment affects bone status and condition, leading to unwanted events such as bone inflammation. Imaging plays a central role in diagnosis; however, radiographic findings are often nonspecific, particularly in early or chronic stages. Each case of osteomyelitis underscores the importance of correlating imaging findings with clinical history and highlights the role of repeated imaging in distinguishing inflammatory bone disease from aggressive jaw lesions. This study aims to characterize diverse patterns of chronic mandibular osteomyelitis associated with various prior treatment modalities using CBCT. By presenting a series of illustrative cases from heterogeneous clinical settings, the authors highlight the nonspecific radiographic features and diagnostic challenges inherent in chronic bone inflammation. The focus remains on the interpretation of complex imaging findings rather than a comparative analysis of technical protocols.

Diagnostics doi: 10.3390/diagnostics16101426

Authors: Pedro Diz Dios Alfonso Souto Míguez Lucía García-Caballero Eliane García Mato Márcio Diniz-Freitas Berta Rivas Mundiña

Conventional: Endodontic outcome criteria established by the American Association of Endodontists (AAE) and the European Society of Endodontology (ESE) rely heavily on radiographic, clinical, and functional parameters. These criteria may not be applicable to patients with special health care needs, who often present with limited cooperation, communication impairments, and altered pain perception. Objective: This study aims to propose an adapted classification system for evaluating non-surgical root canal treatment outcomes in this underserved population. Methods: Based primarily on the criteria established by the ESE and our clinical experience, a novel classification system was developed, delineating three outcome categories grounded in both clinical and radiographic parameters. This framework deliberately excludes the “functional” criterion and introduces a “not assessable” category. It was retrospectively applied to 217 non-surgical root canal treatments performed in 137 patients with special health care needs, each with a minimum one-year follow-up. Outcomes were categorized as “favorable,” “uncertain,” or “unfavorable.” Results: Using the proposed criteria, 87 treatments (40.0%) were classified as “favorable,” 88 (40.5%) as “uncertain,” and 42 (19.3%) as “unfavorable.” By contrast, the application of AAE/ESE standards resulted in a 71.9% “favorable” classification. Most “uncertain” outcomes occurred in patients with neurodevelopmental disorders, where clinical or radiographic evaluation was not feasible. Conclusions: We propose adapted clinical and radiographic criteria for assessing non-surgical root canal treatment outcomes in patients with special health care needs, though broader validation is required. The findings suggest that this procedure remains advisable in this population, with fewer than 20% showing an “unfavorable” long-term outcome.

Diagnostics doi: 10.3390/diagnostics16101425

Authors: Maria-Luiza Băean Oana Nicu-Canareica Cristian Constantin Volovăț Gelu-Adrian Popa Diana Mihaela Ciuc Viorel Jinga Cosmin Medar

Background/Objectives: Autism Spectrum Disorder (ASD) is associated with structural brain alterations, particularly involving white matter and connectivity. Artificial intelligence (AI) enhances the detection of subtle neuroanatomical changes. This study aimed to characterize structural abnormalities and volumetric patterns in children with ASD using AI-assisted MRI. Methods: This retrospective study included 90 children diagnosed with ASD. Brain MRI scans were analyzed using the CE-certified AI platform mdbrain. Structural findings were classified into corpus callosum anomalies, white matter signal abnormalities (WMSA), ventriculomegaly, other abnormalities, or no detectable changes. Group differences were assessed using ANOVA and Kruskal–Wallis tests with Tukey post hoc analysis. Logistic regression, principal component analysis (PCA), and linear discriminant analysis (LDA) were applied. Results: WMSA were identified in 23.3% of patients, followed by other anomalies (27.8%), corpus callosum anomalies (8.9%), ventriculomegaly (8.9%), and no abnormalities (31.1%). Total white matter volume was significantly reduced in pathological groups and was the only independent predictor. PCA identified three principal components reflecting shared temporo-parietal covariance, hemispheric asymmetry, and a white matter-related axis. Exploratory LDA demonstrated partial separation among anomaly categories. Conclusions: Children with ASD in this cohort showed heterogeneous but partially structured MRI alterations involving both focal and global volumetric changes. Reduced total white matter volume was the most consistent multivariable association with structural abnormalities. AI-assisted morphometric analysis may support structural phenotyping in ASD. These findings are exploratory and require confirmation in larger, prospectively validated cohorts before biomarker applications can be considered.

Diagnostics doi: 10.3390/diagnostics16101423

Authors: Çetin Alak Fazil Çağrı Hunutlu Gokhan Ocakoglu Nuray Mammadova Zeynep Kumral Vildan Ozkocaman Fahir Ozkalemkas Dilek Yeşilbursa

Background/Objectives: Hematopoietic stem cell transplantation (HSCT) exposes patients to cardiovascular stress through inflammation, metabolic disturbances, and prior cardiotoxic therapies. Although overt dysfunction is uncommon early after transplantation, subclinical cardiac adaptation remains poorly defined. Methods: We evaluated early electrical and mechanical cardiac responses after HSCT using integrated electrocardiographic (ECG) and echocardiographic assessment. In this prospective cohort study, patients underwent paired pre-transplant and early post-transplant (3–6 months) ECG and comprehensive echocardiography, including tissue Doppler and speckle-tracking analyses of atrial, ventricular, and right heart function. Results: Patients were stratified into multiple myeloma (MM) and non-MM subgroups. ECG voltage increased after HSCT, particularly in MM patients, without changes in left ventricular (LV) mass, geometry, or global systolic indices, suggesting electrical–structural dissociation. Left atrial (LA) reservoir strain decreased despite stable atrial volumes. Diastolic indices showed selective modulation, including a group-time interaction in the lateral e′/a′ ratio without elevated filling pressures. Subgroup analyses suggested divergent myocardial responses, with numerical global longitudinal strain (GLS) improvement in MM patients and reduced LV deformation and right ventricular (RV) fractional area change in non-MM patients. Conclusions: Early cardiac responses after HSCT were heterogeneous and compartment-specific, supporting multiparametric imaging for detection of subclinical cardiac adaptation.

Diagnostics doi: 10.3390/diagnostics16101424

Authors: Lasse Fjordside Mathilde Ørbæk Thomas Bryrup Louise Helvig Kaas Alex Christian Yde Nielsen Nikolai Søren Kirkby Helene Mens Anne-Mette Lebech

Background: Measurements of the B-cell attracting chemokine CXCL13 in cerebrospinal fluid (CSF) has become increasingly popular in the diagnostic work-up for Lyme neuroborreliosis (LNB). ReaScan is a point-of-care test for CXCL13 with a short turnaround-time. However, the diagnostic cut-off value for LNB has not been firmly established. Methods: We conducted a retrospective cohort study including all ReaScan CXCL13 measurements performed on CSF samples at Copenhagen University Hospital, Rigshospitalet, from patients of all ages suspected for LNB in 2020–2025. Patients were categorized in accordance with the European Federation of Neurological Societies (EFNS) diagnostic guidelines for LNB as definite, possible, or non-LNB based on a retrospective review of patient records. The manufacturer-informed cut-off value for positive test results was applied and the diagnostic accuracy was calculated based on the ability to identify patients with possible and definite LNB. In addition, a Youden-index optimized cut-off value was calculated and evaluated on the cohort. Results: A total of 1181 ReaScan CXCL13 measurements from children and adults were evaluated against final diagnoses. Using the manufacturer-informed cut-off value (14 AU/mL) ReaScan CXCL13 reached a sensitivity of 38% and a specificity of 98% for identifying cases of possible and definite LNB. A Youden-index optimized cut-off value (1.79 AU/mL) significantly improved the diagnostic accuracy reaching a sensitivity value of 71% and a specificity of 92%. Conclusions: These real-world clinical data suggest that the current cut-off value for the ReaScan CXCL13 analysis is not optimal for diagnosing LNB. Lowering the cut-off level would significantly increase the diagnostic accuracy.

Diagnostics doi: 10.3390/diagnostics16101421

Authors: Alaa E. S. Ahmed Mostafa E. A. Ibrahim Yassine Daadaa

Background: Cardiovascular diseases (CVDs) are among the top sources of mortality worldwide. To properly diagnose cardiovascular diseases, a low-cost remedy based on phonocardiography (PCG) signals must be proposed. Several deep learning (DL)-driven CVD systems are now being developed to identify various phases of the disease. Nevertheless, the approaches’ accuracy falls short of expectations, and they necessitate substantial processing resources and training data. Methods: This paper proposes Cardio-Dense, a hybrid framework for multi-class CVD detection from phonocardiogram signals. The PCG waveform is first denoised in the wavelet domain and then converted into a 2D time–frequency spectrogram using continuous wavelet transform (CWT). We design a joint architecture that combines a Swin transformer for capturing global contextual dependencies with lightweight DenseBlocks for efficient local feature refinement, enabling robust learning from PCG spectrograms across five disease classes. Results: Experiments on PCG datasets achieve up to 0.977 accuracy, 0.975 sensitivity, 0.992 specificity, 0.978 F1-score, 0.978 AUC, and 0.976 precision, while maintaining low computational overhead suitable for real-time inference. Conclusions: The findings indicate that the proposed model provides an economical, non-invasive method for preliminary signal-level identification of multi-class heart valve diseases. It benefits clinicians by decreasing the need for arduous and error-prone manual PCG analysis. Furthermore, it offers quick, near-real-time categorization suitable for clinical and portable applications.

Diagnostics doi: 10.3390/diagnostics16101422

Authors: Hayoung Ahn Sungwoo Hur Cheol Hyun Lee Se Hun Kang Daeung Ohn SookJung Kim Junghoon Lee Yeon-Jik Choi Jeong-Eun Yi Suk Min Seo Sung-Won Jang Won Hwa Kim Osung Kwon

Background/Objectives: Left bundle branch block (LBBB) remains a common complication after transcatheter aortic valve replacement (TAVR) and is associated with adverse clinical outcomes. However, accurate prediction of LBBB remains challenging due to the complex interactions among the anatomical, procedural, and clinical factors. This study aimed to develop a machine learning (ML)-based framework to predict LBBB and identify relevant contributing features. Methods: In this multicenter retrospective study, we analyzed 242 patients undergoing TAVR across three institutions. A machine learning framework incorporating transformer-based feature selection and conventional classifiers was developed. Model performance was evaluated using accuracy, precision, recall, F1-score, and area under the receiver operating characteristic curve (AUC). Internal validation was performed using bootstrap resampling. Results: The gradient boosting model using ML-derived features demonstrated the most balanced performance, achieving an accuracy of 78.05% and an F1-score of 50.46%, with modest discrimination (AUC 0.61). The ML-based approach identified clinically relevant features, including coronary height, left ventricular outflow tract/annulus ratio, and prosthetic valve size, as well as additional variables not emphasized in conventional analyses. Conclusions: ML-based feature selection can capture complex feature interactions beyond traditional statistical approaches and provide clinically meaningful insights into risk stratification for LBBB after TAVR. Although predictive performance was modest, this approach highlights the potential of ML for improved risk stratification and individualized procedural planning. Further large-scale external validation is warranted.

Diagnostics doi: 10.3390/diagnostics16101420

Authors: Wojciech Michał Glinkowski Paweł Kaminski Rafał Obuchowicz

Background: Missed fractures on initial imaging assessments remain a clinically significant source of diagnostic errors in orthopedic and trauma care. AI-assisted imaging tools are increasingly integrated into fracture detection workflows. However, their diagnostic benefits and safety vary substantially across anatomical regions, clinical contexts, and levels of reader experience. Purpose: To synthesize the current evidence on the diagnostic impact of AI-assisted fracture detection and to discuss evidence-informed principles for safe and selective clinical deployment. Methods: A structured narrative synthesis of meta-analyses, multi-reader, multi-case observer studies, and real-world implementation investigations was performed. Diagnostic performance patterns were examined across anatomical regions and levels of reader experience. No quantitative pooling or reanalysis of the primary data was performed. The findings were synthesized across anatomical regions, reader-experience groups, and implementation-relevant clinical contexts. Results: Across studies, AI-assisted interpretation was generally associated with moderate gains in sensitivity and lower missed-fracture rates compared with unaided human reading, while largely preserving specificity. The diagnostic benefit was greatest among less-experienced readers in high-volume emergency settings. Performance was strongly anatomy-dependent: consistent and clinically meaningful improvements were observed for hip and appendicular skeleton fractures; intermediate benefits with increased false-positive burden were reported for wrist and rib fractures; and inferior sensitivity relative to expert interpretation was documented for cervical and vertebral spine injuries. Conclusions: AI-assisted fracture detection improves diagnostic safety when implemented as a structured second-reader tool; however, its effectiveness depends heavily on anatomy. Available evidence supports selective, risk-stratified deployment, guided by anatomy-specific risk considerations and supervised clinical use, rather than indiscriminate or autonomous use, to maximize benefits and minimize patient safety risks in orthopedic and trauma imaging.

Diagnostics doi: 10.3390/diagnostics16101419

Authors: Eray Abat Ezgi Gizem Abat Yusuf Emrullahoğlu Ramazan Oğuz Yüceer Süleyman Mazıcı Nimetullah Alper Durmuş Ali Şahin Halil Ulutabanca Şükrü Oral Alper Özcan Özlem Canöz Ahmet Küçük

Background: Medulloblastoma is the most common malignant pediatric central nervous system tumor and exhibits marked molecular and clinical heterogeneity. Immune evasion pathways may contribute to tumor aggressiveness and represent potential prognostic and therapeutic targets. We investigated the clinicopathological and prognostic relevance of the immune checkpoint molecules B7-H3 (CD276) and CD47 in medulloblastoma. Methods: We screened 77 patients treated between April 2015 and December 2025; in total, 32 patients with pathologically confirmed medulloblastoma and complete data were included. Tumor B7-H3 and CD47 expression was assessed using immunohistochemistry and an immunoreactivity score (IRS); patients were categorized as having negative/low (IRS < 4) or high (IRS ≥ 4) expression. We analyzed the associations with clinicopathological and molecular features. Overall survival (OS) and disease-free survival (DFS) were evaluated using Kaplan–Meier and log-rank tests. Prognostic factors were examined using univariate and multivariate Cox regression. Results: High B7-H3 expression was associated with shorter OS (median 46 vs. 85 months; p = 0.024) and markedly reduced DFS (median 21 vs. 102 months; p < 0.001). High CD47 expression was also associated with shorter OS (median 56 vs. 102 months; p = 0.025), whereas DFS did not significantly differ by CD47 status (p = 0.200). B7-H3 and CD47 expression levels were not correlated (Spearman’s rho = 0.071; p = 0.699). In the univariate analysis, high B7-H3 expression predicted mortality (HR = 25.79; p = 0.002) and recurrence risk (HR = 136.23; p = 0.045), and high CD47 expression predicted mortality (HR = 4.82; p = 0.042). In the multivariate analysis, high B7-H3 expression remained an independent predictor of poor OS (HR = 31.01; p = 0.004), whereas radiotherapy independently reduced the recurrence risk (HR = 0.197; p = 0.024). Conclusions: B7-H3 is a strong independent adverse prognostic biomarker for OS and is associated with profoundly shorter DFS in medulloblastoma, supporting its relevance as a candidate target for immune-directed strategies.

Diagnostics doi: 10.3390/diagnostics16101415

Authors: Antonio Maccio Manuela Neri Valerio Vallerino Sonia Nemolato Gabriele Sole Elisabetta Pusceddu Paolo Albino Ferrari

Background and Clinical Significance: Rare adnexal tumors with Wolffian or sex cord-like differentiation may undergo major diagnostic reclassification after integrated histologic and molecular review. The contribution of minimally invasive surgery to this process has rarely been described in detail. Case Presentation: We focused on the case of a 33-year-old woman underwent laparoscopic right salpingectomy in October 2021 for a right-sided tubo-adnexal lesion initially diagnosed as adult granulosa cell tumor and later reinterpreted as high-grade endometrioid carcinoma. Completion staging in February 2022 was negative. Positron emission tomography/computed tomography in January 2023 raised concern for recurrence, and exploratory laparoscopy in March 2023 documented peritoneal metastatic disease, followed by four cycles of cisplatin given within the then-prevailing carcinoma-based diagnostic framework. A second laparoscopic reassessment in October 2023 was negative. Because of multifocal abdominal relapse, the patient underwent major cytoreductive surgery in October 2024. Integrated pathologic and molecular review then documented serine/threonine kinase 11 alteration together with forkhead box L2 negativity, favoring classification within the STK11-altered adnexal tumor spectrum. After external review, everolimus plus anastrozole was started in May 2025. Imaging in late 2025 documented persistent pelvic recurrence, and salvage xipho-pubic laparotomy in December 2025 revealed extensive disease involving both ureters, the bladder base, the rectosigmoid wall, and parietal peritoneum; recurrent tissue showed cluster of differentiation 117 positivity. At the most recent available follow-up in April 2026, the patient had no documented death and remained under postoperative surveillance. Discussion and Conclusions: This case illustrates the diagnostic importance of repeated tissue reassessment and the practical value of minimally invasive surgery as a relatively low-burden means of resection, restaging, and tissue acquisition in a rare molecularly reclassified adnexal tumor.

Diagnostics doi: 10.3390/diagnostics16101418

Authors: Changsong Wang Naijun Fan Tian Yun Fulin Li Nianlong Meng Yaxi Wang Junling An Xuexia Lyu

Objectives: Langerhans cell sarcoma (LCS) is a very rare, highly malignant tumor that originates from Langerhans cells. The differential diagnosis of LCS and Langerhans cell histiocytosis (LCH) still faces limitations, and the molecular changes involved in LCS are unclear. Molecular biomarkers and immunophenotypes may help distinguish between LCS and LCH. In this manuscript, the pathological and molecular markers in LCS are explored. Methods: The expression patterns of ASPP1, ASPP2, and inhibitor of apoptosis-stimulating p53 protein (iASPP) were examined using the immunohistochemical method and immunofluorescence staining. Then, genetic features, such as B-Raf proto-oncogene, serine/threonine kinase (BRAF) V600E, K-ras, and ROS proto-oncogene 1, receptor tyrosine kinase (ROS1), were assayed using the amplification refractory mutation system (ARMS) method. Finally, whole-exon sequencing of LCS was performed. Results: Immunohistochemically, in all samples of LCS, ASPP2 was detected in ovoid and elliptic tumor cells. In the case of LCH, ASPP2 was expressed not only in ovoid and elliptic cells but also in histiocytic cells. The expression of iASPP was observed in five cases LCS (5/6), and no positive reaction was observed in the case of LCH. No ASPP1 expression was observed in LCH and LCS. During triple-color immunofluorescence analysis, ASPP2 and iASPP were co-expressed on Langerin+ LCS tumor cells. No mutations of BRAF V600E, K-ras, or ROS1 were detected in LCH and LCS. No gene mutation or rearrangement was detected in LCS except for the MAP2K1 gene. The mutation site was nonsynonymous in 607 bp of MAP2K1, resulting in a change from base G to A; thus, the amino acid E changed to K at the 203 site (4/6, 66.67%). Conclusions: Combined detection of ASPP2 and iASPP in tissue samples may provide valuable markers to differentiate between LCH and LCS. The MAP2K1 variants c.607G > A is the first potential marker to be reported in LCS.

Diagnostics doi: 10.3390/diagnostics16101416

Authors: Nikolaos Anagnostou Chris Kalogeropoulos Panagiotis Kanavaros Alejandra de-la-Torre Sofia Androudi Panos Kakoulidis Rafael Tierradentro-Alape Dimitrios Kalogeropoulos

The scope of the present study is to conduct a comprehensive review of the anatomy, function, major pathological conditions and clinical significance of ocular lymphatic vessels. In recent years, it has become evident that ocular lymphatics play a major role in the pathogenesis and progression of ocular disorders. Therefore, we delved into this emerging field and described newly proposed mechanisms that may explain the involvement of ocular lymphatics in healthy and pathological states. Lymphatics are present in a plethora of ocular tissues primarily under pathological conditions, including limbal stroma, optic nerve, ocular muscles, lacrimal glands and sclera. The conjunctiva contains an extensive lymphatic network, whereas the cornea and retina are typically devoid of lymphatic vessels under physiological conditions. Inflammatory conditions can give birth to nascent lymphatic vessel sprouting. Growing evidence emphasizes the role of ocular lymphatics in glaucoma pathogenesis, suggesting a previously unknown aqueous humor drainage pathway mediated by lymphatic contribution. This review is based mainly on evidence from animal and experimental models, as human clinical data remain limited; therefore, caution is warranted when translating these findings into clinical practice. By gaining insight into the mechanisms and the clinical significance of eye lymphatics, this review aims to address novel insights for future research and treatment of eye diseases, as well as to highlight a misconception that has persisted for decades in ophthalmology.

Diagnostics doi: 10.3390/diagnostics16101417

Authors: Andreas Kjaer

It is with pleasure that we announce the launch of a new section of Diagnostics, named “Forensic Diagnostics” [...]

Diagnostics doi: 10.3390/diagnostics16101414

Authors: Eugen Silviu Bud Mariana Păcurar Cristina Ioana Bica Sorana Maria Bucur Alexandru Vlasa Beáta Szabó Anamaria Bud

Background: Skeletal deep bite malocclusion (Angle Class II division 2) represents a common vertical skeletal discrepancy characterized by excessive anterior overbite and a hypodivergent craniofacial growth pattern. The contribution of cranial base morphology to mandibular growth direction during early development remains incompletely understood. Objective: To evaluate the relationship between cranial base morphology and maxillofacial growth patterns in children with skeletal deep bite, using a longitudinal cephalometric approach. Materials and Methods: This retrospective longitudinal cohort study included 96 prepubertal patients aged 7–10 years (54 with skeletal deep bite, 42 Angle Class I dentoalveolar controls). Skeletal deep bite was defined by overbite > 4 mm and mandibular plane angle (FMA) < 22°. A total of 298 standardized lateral cephalometric radiographs (2–4 per subject; mean follow-up 24 ± 4 months) were analyzed. Twenty-two cephalometric parameters were assessed. Longitudinal changes were evaluated using repeated-measures analysis, and predictors of deep bite severity were identified using multiple linear regression. Results: Compared with controls, the deep bite group exhibited significantly reduced mandibular plane angle (18.5° vs. 24.0°), smaller gonial angle (104.3° vs. 111.0°), and decreased lower anterior facial height (86.3 mm vs. 92.0 mm; all p < 0.001). Differences in cranial base morphology were modest, including reduced anterior cranial base length (58.6 mm vs. 60.0 mm; p = 0.031). Regression analysis identified gonial angle and lower anterior facial height as significant predictors (R2 = 0.58). Longitudinal analysis suggested early tendencies toward forward mandibular rotation and reduced vertical growth rate over the observation period. Conclusions: In prepubertal children, skeletal deep bite is associated with early tendencies toward reduced vertical facial development and forward mandibular rotation. Cranial base morphology appears to be associated with mandibular growth direction as a secondary modulatory factor rather than a primary determinant. Early identification of hypodivergent growth indicators may facilitate timely interceptive orthodontic strategies.

Diagnostics doi: 10.3390/diagnostics16101413

Authors: Camila Vilas Boas Machado Pedro Paulo Teixeira da Silva Torres Danilo Tadao Wada Francisco Aristofanes Coelho Sarmento Neto Maria Carolina de Oliveira Rodrigues Marcel Koenigkam-Santos

Background/Objectives: Interstitial lung disease (ILD) is the main thoracic manifestation of connective tissue diseases (CTDs) and is associated with high morbidity and mortality. High-resolution computed tomography (HRCT) of the chest is considered the gold standard imaging method for detecting and accurately characterizing ILD. This study aims to perform longitudinal visual and quantitative analyses of HRCT scans of patients with ILD secondary to CTD (ILD-CTD) and to correlate these findings with clinical outcomes (functional decline and death) in order to identify tomographic prognostic markers. Methods: This retrospective and longitudinal study included 195 patients with CTD who underwent HRCT at baseline and after two follow-ups. Data collected included initial disease extent and subjective impression of progression, as well as quantitative parameters such as lung volume and mean lung density. Forced vital capacity (FVC) and diffusion capacity of carbon monoxide (DLCO) values were also recorded, along with information on patient outcome. Results: Quantitative and visual assessments demonstrated moderate agreement in estimating ILD extent. Variations in lung volume, ground-glass index, pulmonary vascular volume-to-lung volume ratio, and disease extent correlated with subjective perception of disease progression. Lung volume reduction and increased disease extent were associated with FVC decrease at follow-up 1, whereas an increased fibrosis index correlated with reduced FVC at follow-up 2. No quantitative parameter was associated with mortality risk. Conclusions: The results support the potential benefit of using quantitative CT analysis as a complementary tool to pulmonary function tests and visual analysis in the longitudinal evaluation of ILD-CTD.

Diagnostics doi: 10.3390/diagnostics16091412

Authors: Filippo Pesapane Anna Rotili Silvia Penco Valeria Dominelli Francesca Priolo Irene Marinucci Luca Nicosia Roberto Grasso Gabriella Pravettoni Enrico Cassano

Background: Explainable artificial intelligence (XAI) is increasingly proposed to improve trust in mammography-based artificial-intelligence systems, but the validity and clinical readiness of published explanations remain unclear. We aim to systematically review XAI methods applied to mammography and synthesize how explanations are evaluated for validity, robustness, and clinical usefulness. Methods: We conducted a systematic review according to PRISMA 2020. MEDLINE/PubMed, Embase, Scopus, Web of Science Core Collection, and the Cochrane Library were searched from 1 January 2015 to 15 January 2026. Two reviewers independently screened records and extracted data; disagreements were resolved by consensus with a third reviewer. Included studies used mammography as the primary input and reported an explicit explanation or interpretability mechanism. Because the literature was methodologically heterogeneous, we performed a structured narrative synthesis and an adapted XAI-specific appraisal of explanation claims, quantitative evaluation, external validation, human-factor assessment, and reporting transparency. Results: Fourteen studies were included. Ten studies addressed detection or lesion classification and four addressed risk or outcome prediction. Primary XAI families were interpretable-by-design architectures (6/14), post hoc saliency or attribution methods (5/14), and feature-level explanation methods (3/14). Five studies remained at tier-1 qualitative plausibility only, seven reached tier-2 internal quantitative explanation evaluation, two reached tier-3 external or cross-dataset interpretability assessment, and none reported reader or workflow studies. In the dedicated mammography saliency benchmark, Pointing Game scores for Grad-CAM, Grad-CAM++, and Eigen-CAM ranged from 0.30 to 0.41, indicating only modest lesion-pointing reliability despite acceptable classifier performance. Conclusions: Mammography XAI remains dominated by visually plausible explanations that are inconsistently validated. The literature is moving toward task-aligned and intrinsically interpretable designs, yet external validation and clinician-centered evaluation remain rare. Future studies should pre-specify explanation claims, use task-appropriate quantitative metrics, report explanation robustness under distribution shift, and test whether explanations improve human decision-making.

Diagnostics doi: 10.3390/diagnostics16091410

Authors: Augustina Mozerytė Juozas Jarašūnas Kipras Mikelis Eimantas Dumskis Donatas Jocius

Background/Objectives: CT-guided transthoracic lung biopsy is a broadly performed and minimally invasive procedure for obtaining tissue samples from pulmonary lesions, offering a high diagnostic yield, and remains a cornerstone of accurate lung cancer diagnosis. The primary objective of this study was to assess the diagnostic yield of CT-guided transthoracic lung biopsies and to investigate the factors influencing this yield, with procedure-related complications being a secondary objective. Methods: A retrospective study was conducted on 356 CT-guided transthoracic lung biopsies performed between January 2021 and December 2023. The patient demographics, lesion characteristics (size, location) and histological findings were analyzed. The diagnostic yield was evaluated based on histological findings and, if necessary, follow-up information. Results: Of the 356 biopsies, 326 (91.6%) were found to be diagnostic, and 30 (8.4%) were non-diagnostic. The diagnostic yield was significantly influenced by lesion size and the number of biopsy cores, with lesions ≤2 cm associated with a higher diagnostic failure rate (p = 0.034). A significant interaction was also observed between lesion size and core number (p < 0.001). The overall complication rate was 11.5%, with pneumothorax being the most frequent event (7.0%). CIRSE grade 2 and grade 3 complications occurred in 4.8% and 3.1% of cases, respectively. Solid lesion morphology was identified as an independent predictor of complications (OR = 1.67, p = 0.022). Conclusions: In summary, CT-guided transthoracic lung biopsy demonstrates a high diagnostic yield with an acceptable safety profile and remains an important diagnostic tool in the evaluation of pulmonary lesions.

Diagnostics doi: 10.3390/diagnostics16091411

Authors: Raffaela Miriam Planka Almuthe Christine Hauer Sebastian Bauchinger Benno Kohlmaier

Background: Due to dysbiosis, intestinal barrier dysfunction, and immunosuppressive therapy, pediatric inflammatory bowel disease (PIBD) patients are more susceptible to infections. However, data on bacterial gastrointestinal (GI) infections in this population are scarce, and no guidelines explicitly address immunosuppressive therapy management during such infections. This single-center study aims to address these knowledge gaps. Methods: A retrospective study of bacterial GI infections was conducted in PIBD patients aged 0–18 years, treated between 2011 and 2021 at the Department of Pediatrics and Adolescent Medicine, Medical University of Graz. Data to assess the study endpoints were extracted from the hospital information system. Results: A total of 139 PIBD patients were screened for bacterial GI infections. The mean follow-up time was 49 months (standard deviation ±33) and the total follow-up time amounted to approximately 473 person-years. Fourteen patients developed infections, with three experiencing them twice, resulting in 17 cases of infection. Most infections were caused by opportunistic bacteria, and 10 infections were treated with antibiotics (11 antibiotic prescriptions in total). At infection onset, 12 patients were on (combined) immunosuppressive therapy, including corticosteroids (3 patients), immunomodulators (9 patients), and/or biologics (3 patients). Six infections required escalation of immunosuppressive therapy due to increased PIBD activity. Hospitalization was required in five cases, and one Clostridioides difficile infection progressed to sepsis, necessitating intensive care unit admission. This corresponds to an incidence of three infections (95% confidence interval 1.75–4.80) and 0.2 severe infections per 100 person-years (95% confidence interval 0.01–1.11). Conclusions: The incidence of bacterial GI infections was 3 per 100 person-years (95% confidence interval: 1.75–4.80), with most cases being clinically mild. Clostridioides difficile was the most common pathogen. Immunosuppressive therapy was generally continued or intensified, when necessary, while antibiotic therapy was administered as indicated.

Diagnostics doi: 10.3390/diagnostics16091409

Authors: Juan C. Restrepo Maria L. Bolanos Seungik Baek Satish C. Muluk Mark K. Eskandari Vikram S. Kashyap Eanas Yassa Ender A. Finol

Background/Objectives: Abdominal aortic aneurysm (AAA) surveillance is based largely on monitoring the maximum diameter, a single scalar metric that obscures regional remodeling and offers limited information on the location and time dependency of the growth rate. The present work addresses this limitation with a geometry-based patient-specific framework that learns local, linear evolution from longitudinal clinical imaging, yielding 3D forecasts of AAA geometry at arbitrary future times. Methods: Lumen and outer wall surfaces are represented on a centerline-anchored cylindrical grid, with subsequent implementation of individualized linear mixed-effects models. The model is explicitly interpretable as the fixed effects predict global trends and the random effects represent regional heterogeneity. In a multicenter cohort of 79 patients, we evaluated forecasts using spatial similarity (with the 95th percentile of the Hausdorff distance—HD95) and clinically relevant global geometric scalars such as maximum diameter and volume. Results: When forecasting a future AAA geometry, the model achieved sub-millimetric HD95 spatial errors and less than 6% error for the aforementioned global scalars. The model was deployed in an interactive application named the Aneurysm Forecasting Studio, which allows a user to visualize the AAA in an explorable forecast space. Conclusions: During typical clinical surveillance intervals, AAA geometric remodeling is reasonably approximated as locally linear in time, enabling transparent, fast forecasts that support surveillance optimization, threshold timing, and digital twin-based interventional planning.

Diagnostics doi: 10.3390/diagnostics16091408

Authors: Iulia Stratulat-Chiriac Raluca Ozana Chistol Lăcrămioara Perianu Elena Țarcă Viorel Țarcă Alina Mariela Murgu Paula Popovici Ioana-Alina Halip Elena Cojocaru Valeriu Chisălău Cristina Furnică

Background/Objectives: Congenital gastrointestinal malformations (CGIMs) are important causes of neonatal surgical morbidity with potential long-term consequences. Although some can be suspected on prenatal ultrasound, data on their clinical spectrum, burden, and distribution remain limited in Eastern Europe. This study aimed to describe the diagnostic spectrum, timing of diagnosis, documented prenatal ultrasound suspicion, and the early outcomes of CGIMs managed at a Romanian tertiary referral centre between 2020 and 2024, a period overlapping the COVID-19 pandemic. Methods: We conducted a retrospective, single-centre observational study including all consecutive paediatric patients with a CGIM admitted between January 2020 and December 2024. Cases were analysed by index anatomical diagnosis, phenotypic complexity, and etiologic background. Logistic regression was used to examine factors associated with documented prenatal suspicion and in-hospital mortality, and annual hospital-based CGIM admission rates were modelled with Poisson regression, using the number of paediatric surgical admission as the offset. Results: Among the 231 children (58.9% male), the most frequent diagnoses were persistent omphalomesenteric duct remnants (16%), oesophageal atresia with or without tracheoesophageal fistula (15.6%), and anorectal malformations (13.9%). Documented prenatal ultrasound suspicion was present in 17.7% of pregnancies (41/231) and was likely underestimated because antenatal documentation was unavailable for 17.7% of the cohort. The highest proportions of documented prenatal suspicion were observed in jejuno-ileal and duodenal atresia. Foregut malformations were the most common by embryological grouping (93/231, 40.3%). Most cases were diagnosed during the neonatal period (n = 161, 69.7%). CGIM admission rates per 1000 surgical admissions ranged from 20.8 to 38.2. An exploratory Poisson model yielded a hospital-based rate ratio per calendar year of 0.88 (95% CI 0.81–0.97; p = 0.008). However, given the limited number of annual observations and increasing total surgical admissions, this finding should be considered exploratory and hypothesis-generating only. Complex cases accounted for 8.2% and associated extra-intestinal anomalies were present in 70.1%. In-hospital mortality was 13.0% and occurred predominantly in patients with complex or foregut malformations. In the primary complete-case multivariable model, prematurity remained independently associated with mortality, whereas complex CGIMs were not independently associated with mortality after adjustment. A prespecified multiple-imputation sensitivity analysis yielded a stronger estimate for complex CGIMs, but this finding was interpreted cautiously and not treated as a primary result. Conclusions: In this tertiary referral cohort, documented prenatal suspicion of CGIM was low and strongly diagnosis-dependent, while most cases were identified in the neonatal period. Mortality was concentrated in foregut and clinically complex presentations in the descriptive analysis, while prematurity remained independently associated with death in the primary multivariable model. These findings highlight the need to strengthen prenatal referral pathways and coordinated national surveillance.

Diagnostics doi: 10.3390/diagnostics16091407

Authors: Francesco Sessa Clelia Grippaldi Massimiliano Esposito Carlos A. Gutierrez Emina Dervišević Efehan Ulas Federica Ministeri Lucio Di Mauro Matteo Bolcato Cristoforo Pomara Monica Salerno

Background/Objectives: Accurate post-mortem interval (PMI) estimation becomes increasingly difficult when bodies decompose under extreme heat. Hyperthermal Mediterranean environments accelerate soft-tissue degradation, induce early mummification, and distort classical thanatological indicators, often resulting in substantial PMI overestimation. This study analyzes three forensic cases affected by climate-driven decomposition anomalies and presents a climate-adaptive, AI-assisted diagnostic framework applied uniformly across all cases to improve PMI interpretation. Methods: A retrospective case series analysis was conducted on three individuals recovered during summer heatwaves. Crime scene investigation, post-mortem computed tomography (PMCT), autopsy, and genetic identification were integrated with 5–15-year meteorological datasets. Classical PMI estimations were compared with circumstantial data. A multimodal AI model, incorporating environmental features, decomposition morphology, and microenvironmental modifiers, was operationalized for each case using a hybrid Random Forest–LSTM architecture. Engineered indices included Accumulated Degree Days (ADD), a Decomposition Index, and climate-stress metrics (Thermal Load Index, Desiccation Pressure Factor, Microenvironmental Distortion Coefficient). Quantile regression provided calibrated prediction intervals. Results: Morphological assessments overestimated PMI in every case, suggesting intervals of 1–6 months despite true PMIs of approximately 20 days (Cases 1–2) or 36–48 h (Case 3). The AI model yielded conceptual outputs more consistent with verified PMIs, ~21 days (Case 1), ~23 days (Case 2), and ~42 h (Case 3), each accompanied by 50% and 90% prediction intervals. Explainability analyses identified thermal load, desiccation pressure, and microenvironmental distortion, particularly insulation in Case 3, as dominant drivers. Conclusions: Extreme heat fundamentally alters decomposition trajectories, rendering classical PMI methods unreliable. Applying a climate-aware, AI-assisted diagnostic framework across all three cases improved interpretability, providing uncertainty-aware estimates aligned with true PMIs. The AI framework is presented as a conceptual, non-trained, proof-of-concept system, and reported outputs represent operational demonstrations rather than validated predictions, offering a promising foundation for next-generation PMI diagnostics in hyperthermal forensic settings.

Diagnostics doi: 10.3390/diagnostics16091406

Authors: Busra Pirinc Ayse Gamze Ozcan Ekrem Solmaz Betul Sevindik Emine Uysal Zeliha Fazliogullari

Background: The spleen is an important organ in the evaluation of systemic diseases due to its hematologic and immunologic functions. Changes in splenic volume and surface area have diagnostic significance in various clinical conditions. This study aimed to evaluate age- and sex-related changes in splenic volume and surface area in an adult population. Material: A total of 304 abdominal CT scans (153 females, 151 males) were retrospectively evaluated. Participants aged 19–89 years were stratified by decades. Changes in splenic surface area and volume were analyzed according to age and sex using measurements obtained from these images with the 3D Slicer software package. Results: Splenic volume showed significant differences across age groups in females, whereas no statistically significant age-related difference was observed in males. Splenic surface area differed significantly according to age groups in both sexes. The highest mean splenic volume and surface area were observed in the 19–29 age group in both sexes. The lowest mean values were detected in the 80–89 age group in females and in the 70–79 age group in males. Conclusions: Splenic volume is higher in males than in females. A statistically significant decrease in splenic volume with advancing age was observed in females, whereas only a non-significant decreasing trend was noted in males. A marked reduction in splenic volume and surface area was observed particularly after the age of 70 years. This finding is associated with age-related immune decline and functional hyposplenism and carries clinical significance in terms of increased susceptibility to infections and diminished immune response in elderly individuals. Furthermore, splenic shrinkage should be considered in the assessment of hematological reserve and in the differentiation of changes related to chronic diseases.

Diagnostics doi: 10.3390/diagnostics16091402

Authors: Karina Felippe Monezi Pontes Liliam Cristine Rolo Gustavo Yano Callado Alberto Borges Peixoto Manoel Sarno Alex Sandro Rolland Souza Francisco Herlânio Costa Carvalho Antonio Braga Edward Araujo Júnior

Objective: This study aimed to describe gestational age-specific biometric and estimated fetal weight (EFW) patterns derived from a multicenter cohort of fetuses with gastroschisis and to evaluate the agreement between prenatal EFW and birth weight. Methods: This retrospective study included singleton pregnancies with a prenatal diagnosis of gastroschisis and at least two ultrasound evaluations between 20 and 37 weeks. Data were collected from four Brazilian tertiary centers between 2010 and 2024. Biometric parameters (biparietal diameter, head circumference [HC], abdominal circumference, and femur length) and EFW were recorded. EFW was calculated using Hadlock IV and Siemer formulas. Polynomial regression models were applied to generate gestational age-specific curves for HC, femur length (FL), and EFW. Agreement between prenatal EFW and birth weight (in cases assessed within 14 days of delivery) was analyzed using Bland–Altman plots and the concordance correlation coefficient (CCC). Results: A total of 116 pregnancies and 355 ultrasound tests were included. Polynomial models showed a strong association between gestational age and EFW (R2 = 0.837 for Siemer; R2 = 0.728 for Hadlock), HC (R2 = 0.849), and FL (R2 = 0.877). The 50th percentile curves for gastroschisis were consistently lower than those from standard growth charts. In the birthweight concordance analysis (n = 46), the Siemer formula showed low agreement (CCC = 0.55), while the Hadlock formula showed even lower concordance (CCC = 0.44), with both formulas underestimating actual birth weight. Conclusions: Fetuses with gastroschisis have distinct growth patterns not captured by standard references. Tailored growth curves and careful interpretation of EFW are essential to improve prenatal assessment in this population.

Diagnostics doi: 10.3390/diagnostics16091404

Authors: Khahliso Genious Seekoei Nape Matheko Phahlamohlaka Jeanette Du Plessis Setlhapelo Edward Mokhure

Introduction: Computed Tomography (CT) brain imaging provides high-resolution anatomical detail but involves relatively higher radiation doses, necessitating dose monitoring and optimisation. Diagnostic reference levels (DRLs) are recommended dose indicators for optimising radiation exposure without compromising diagnostic image quality; however, national DRLs for CT brain imaging have not yet been established in South Africa. This article presents a protocol for establishing local DRLs for non-contrast- (non-CE) and contrast-enhanced (CE) adult CT brain examinations at an academic hospital in Johannesburg, South Africa. Materials and Methods: The research site is at a single hospital in Johannesburg, South Africa. The research design for this study is retrospective. A sample of 197 adult CT brain examinations (63 non-CE, 34 CE, and 100 combined non-CE and CE examinations) performed between 1 January and 31 December 2024 will be used to develop local DRLs. The 64-slice CT scanner of choice for data collection is the Siemens SOMATOM Definition AS. The population defined for this study is individuals aged 18–70 years. The preferred contrast media used for CT brain examination at the research site is 40 mL of Omnipaque 350. The scan range for CT brain is from the base of the skull (foramen magnum) to the vertex, ensuring full coverage of intracranial structures. Dose metrics, including the volumetric CT dose index (CTDIvol) and dose–length product (DLP), will be extracted from archived dose reports. Local DRLs will be established as the 75th percentile values of CTDIvol and DLP for each protocol group. Descriptive statistics (mean, median, and interquartile range) will be used to summarise the data demographics. The effective dose will be estimated by applying a head-specific conversion coefficient to the DLP values. Results: As this is a study protocol, results are not yet available. Local DRLs will be reported as the mean, median, and 75th percentile values of the DLP and CTDIvol for non-CE, CE, and for both non-CE and CE CT brain examinations. The effective dose will be estimated by applying a head-specific dose conversion coefficient (k-factor) to the mean DLP values. Expected Outcomes: This study is expected to establish local DRLs for adult CT brain examinations, providing baseline data for dose optimisation and supporting the future development of national DRLs in South Africa. Conclusions: Establishing local DRLs will support the optimisation of the radiation dose in CT brain imaging to keep the dose as low as reasonably achievable. The DRLs developed for this study will contribute to national and international efforts toward optimising radiation dose during diagnostic X-ray imaging investigations.

Diagnostics doi: 10.3390/diagnostics16091405

Authors: Jonas Reis Marco Öchsner Chiara Adam Thomas D. Fischer Thomas Liebig Robert Forbrig

Background/Objectives: Contrast enhancement (CE) on T1-weighted MRI is routinely used to guide therapy in the management of glioblastoma, although adjacent non-contrast-enhancing (non-CE) T2/FLAIR abnormalities can also harbor viable tumor tissue. The differences between these radiographic compartments remain incompletely characterized beyond conventional structural imaging. We therefore compared CE and non-CE compartments in untreated IDH-wildtype glioblastoma using dynamic susceptibility contrast (DSC) and diffusion-weighted MRI derived indices. Methods: Adults with untreated glioblastoma imaged preoperatively between January 2021 and September 2024 on multi-vendor 1.5 T and 3 T scanners were retrospectively included. Regions of interest were placed in CE tumor, adjacent non-CE T2/FLAIR hyperintense tissue, and contralateral normal-appearing white matter (NAWM). Mean apparent diffusion coefficient (rADC), cerebral blood volume (rCBV), capillary transit time heterogeneity (rCTH), oxygen extraction fraction (rOEF), and a cerebral metabolic rate of oxygen index (rCMRO2) were extracted and harmonized for scanner effects and normalized to NAWM. Paired CE–non-CE differences were tested using Wilcoxon signed-rank tests and summarized by Hodges–Lehmann differences with bootstrap 95% confidence intervals. Spearman correlations were used to assess coupling within contrast-enhancing tumor regions. Results: Seventy-two participants were analyzed (median age 67 years; 34 women); 66 had paired CE and non-CE data. rCMRO2 and rCBV were higher in CE than non-CE (both p < 0.001), while rADC was lower (p = 0.003). rOEF (p = 0.12) and rCTH (p = 0.52) did not differ significantly between compartments. Conclusions: CE in untreated IDH-wildtype glioblastoma predominantly reflects higher perfusion capacity (rCBV) along with a higher model-derived rCMRO2 index, while capillary-function indices (rCTH and rOEF) are not consistently compartment-restricted. These findings may refine the physiological interpretation of CE in glioblastoma and support further validation of DSC-derived indices.

Diagnostics doi: 10.3390/diagnostics16091403

Authors: Mark Jain Elena Mladova Pavel Zalepaev Margarita Gundobina Alexander Klimov Liya Shcherbakova Larisa Samokhodskaya Olga Panina

Background: There is growing evidence that uterine microbiota might be linked to endometrial receptivity (ER) and affect the outcome of assisted reproductive technology (ART) procedures. Owing to the invasive nature of endometrial sampling, the evaluation of microbiota in this biomaterial is only possible outside the embryo transfer (ET) cycle. However, menstrual blood might be the key to overcoming this challenge as it can be safely aspirated from the uterine cavity at the beginning of the target ET cycle. This study aimed to evaluate the association of the microbiological profiles of menstrual blood with ER in patients undergoing frozen ET. Methods: Menstrual blood was obtained from 98 individuals scheduled for frozen ET in a private ART clinic (ET success rate–50%). DNA was isolated from menstrual sediment and analyzed using a multiplex quantitative PCR assay designed to identify 28 relevant microbial taxa and 3 Herpesviridae viruses. Results: Bacterial DNA was detected in 75.5% of samples. There were no associations between the abundance of individual microbial taxa and the outcome of ET, and the same was true for Shannon’s α-diversity indices (p > 0.05). However, Candida spp. and Enterobacteriaceae were detected exclusively in patients with negative ET outcomes (p = 0.028). Individuals with recurrent implantation failure had a significantly lower abundance of Lactobacillus spp. than the rest (0.0 [0.0; 7.4] vs. 2.8 [0.0; 91.9] %, p = 0.024). Conclusions: Menstrual blood aspirated directly from the uterus is a promising biomaterial for endometrial microbiological profiling. Upon further investigation, its analysis might become a useful tool in managing infertile patients scheduled for ART treatment.

Diagnostics doi: 10.3390/diagnostics16091401

Authors: Konstantina Bolou George Triantafyllou Nikolaos-Achilleas Arkoudis Panagiotis Papadopoulos-Manolarakis Irini Chatziralli Vasileios Papadopoulos Georgios Velonakis Maria Piagkou

Background/Objectives: Oculomotor nerve palsy (OMNP) is a clinically significant condition that may represent the earliest manifestation of life-threatening intracranial pathology, particularly aneurysmal compression or neoplasia. Despite its neurosurgical relevance, comprehensive meta-analytic evidence synthesizing OMNP etiologies, clinical presentation, and contemporary diagnostic pathways remains limited. Methods: Following PRISMA 2020 guidelines, MEDLINE, Scopus, and Web of Science were systematically searched for studies reporting quantitative data on OMNP. Pooled prevalence estimates were calculated using random-effects models for causes and symptoms, while a structured narrative synthesis was performed for diagnostic modalities because outcome reporting was heterogeneous and unsuitable for meta-analysis. Risk of bias was assessed using the Joanna Briggs Institute (JBI) risk of bias tool. Results: Twenty-four studies involving 5541 patients were included. Using a multivariate multilevel model to account for within-study dependence, the most common etiological category was vascular disorders (35.62%), followed by idiopathic (16.47%) and neoplastic (12.10%). Head trauma and aneurysms accounted for 11.26% and 10.08% of cases, respectively. Diplopia (60.63%) and ptosis (54.12%) remained the predominant clinical symptoms, while pupil involvement was identified in 40.62% of the pooled population. Diagnostic paradigms have shifted decisively toward non-invasive neuroimaging, with magnetic resonance imaging reported in 66% of included studies and magnetic resonance or computed tomographic angiography increasingly employed to identify surgically relevant vascular lesions. Conclusions: Although vascular disorders represented the most common etiological category, the notable prevalence of aneurysmal and neoplastic causes underscores the importance of prompt high-resolution neuroimaging and early neurosurgical assessment. Early recognition and etiological stratification remain essential to optimize management and prevent irreversible neurological morbidity.

Diagnostics doi: 10.3390/diagnostics16091400

Authors: Hon-Man Liu Wei-Lung Tseng

Background and Purpose: Understanding regional differences in acute ischemic stroke (AIS) lesions, particularly between cortical and basal ganglia (BG) regions, is crucial for enhancing diagnostic precision and therapeutic strategies. This study builds upon prior research in CT-based stroke imaging by introducing entropy and SD as novel biomarkers for lesion differentiation and focuses on their temporal evolution to identify critical diagnostic windows for clinical management. Methods: We retrospectively analyzed imaging data from 45 AIS patients (27 cortical, 18 BG lesions). Time-histogram metrics—standard deviation (SD), skewness, kurtosis, and entropy—were computed for lesions in both regions across multiple time points post-stroke. Statistical comparisons utilized one-way ANOVA and post hoc t-tests (p < 0.05). Results: Cortical lesions exhibited significantly higher entropy (4.34 vs. 3.99, p = 0.000034) and SD (5.16 vs. 3.94, p = 0.000144) compared to BG lesions, reflecting greater heterogeneity. No significant differences were found in skewness or kurtosis. Peak diagnostic sensitivity occurred at 76–87 min post-stroke (p < 0.001). Temporal trends revealed increasing divergence in entropy and SD between cortical and BG lesions during this window. The identification of the 76–87-min diagnostic window offers critical insights into the hyperacute phase, where early ischemic changes are often subtle on NCCT. Conclusions: SD and entropy are robust biomarkers for distinguishing cortical and BG lesions in AIS, offering insights into regional tissue responses and temporal evolution, with potential for personalized stroke care. These metrics could serve as standalone biomarkers or be integrated into AI-based NCCT triage systems to enhance lesion characterization and therapeutic decision-making.

Diagnostics doi: 10.3390/diagnostics16091399

Authors: Osama M. K. Edris Abdulgaffar Bashir Adam Emad Ali Albadawi Ahmad Mahroos ALGhabban Razan Saad M. Alqarni Wejdan Hussain Owaydhah Omar A. Alharthi Eyad Khattab Fahd Alharbi Yasir Hassan Elhassan

In the original publication [...]

Diagnostics doi: 10.3390/diagnostics16091398

Authors: Emma Sokolova Olav Goetz Ketija Grīnberga Sevinc Elif Sen Kaspars Kupics Aija Mača-Kalēja Ainārs Rudzītis Daiga Behmane Oskars Kalējs

Background: Atrial fibrillation (AF) significantly impacts the clinical and financial burden of healthcare systems worldwide. Patient-reported outcomes (PROMs) are considered a core element of patient-centered care. However, the integration of PROMs into AF clinical pathways remains limited. Objectives: In this study, we aimed to develop a policy-oriented framework for integrating PROMs into AF management, building on QoL assessment and the AF-CARE pathway. Methods: We compared the selected instruments (AFEQT, SF-36, EQ-5D, and AFSS) to examine how different QoL domains are represented. We then considered how the missing domains relate to routine care and healthcare delivery. On this basis, we constructed a conceptual framework linking PROM domains with clinical and policy decisions, as well as with diagnostic and follow-up strategies in AF. Results: Existing PROMs capture symptom burden reasonably well, but they do not fully reflect several domains that shape the daily experience of patients with AF, including cognition, sleep quality, sexual health, and economic burden. The proposed framework places PROMs within the AF-CARE components and illustrates how they can be used in routine practice—not only for long-term monitoring, but also to improve clinical decision-making, and better align with value-based healthcare strategies at both the clinical and system levels. It also outlines a practical approach to incorporating PROMs into everyday care and into broader health-system decision-making. Conclusions: Integrating PROMs into AF-CARE requires a system-level redesign rather than isolated tool implementation. Within the proposed framework, the question is no longer whether PROMs should be used in AF care, but how to integrate them in a way that meaningfully influences clinical decisions and patient outcomes.

Diagnostics doi: 10.3390/diagnostics16091397

Authors: Kazuyuki Yusa Nobuyuki Sasahara Tomoharu Hemmi Satoshi Kasuya Kenta Kagami Kotaro Taniguchi Shigeo Ishikawa

Background/Objectives: The aim of this study was to investigate the association between patient demographics and overall operating time during bilateral sagittal split osteotomy (BSSO). Methods: For this retrospective study, data were collected from patients who had undergone BSSO in our hospital between 2016 and 2023. The mandibular body and mandibular ramus were evaluated from preoperative computed tomography (CT), and CT attenuation values of cortical and cancellous bone in the mandibular ramus were obtained from standardized preoperative CT images. Patient demographics (age, sex, occlusal class, and body weight) before surgery were also collected from the medical record. Results: Forty-six patients were included in this study. Weight and CT attenuation of the mandibular ramus (both cortical and cancellous bone) correlated with operating time (weight: rs = 0.304, p = 0.04; CT attenuation of mandibular ramus: rs = 0.323, p = 0.029). In addition, the Mann–Whitney U test revealed significantly greater operating time in males (p < 0.05). Effects of each variable were estimated after adjusting for other variables, and CT attenuation of the mandibular ramus (both cortical and cancellous bone) (B = 0.088, p = 0.008) was identified as having an effect on operating time. Higher CT attenuation, reflecting greater cortical and cancellous bone density, may increase resistance during osteotomy and consequently prolong operating time. Conclusions: This pilot study observed a possible association between CT attenuation of the mandibular ramus and operating time in BSSO. However, these findings are preliminary and do not imply any causal relationships. Thus, further studies with larger cohorts are required to confirm these observations.

Diagnostics doi: 10.3390/diagnostics16091396

Authors: Achim Langenbucher Jascha Wendelstein Nóra Szentmáry Alan Cayless Anika Förster Peter Hoffmann Suphi Taneri

Background/Objectives: The purpose of this study was to investigate the variation in subjective manifest refraction measures in a patient cohort screened for myopic refractive surgery. Methods: In this retrospective non-randomised cross-sectional single-centre study, we evaluated a dataset containing sequences of three refraction measurements performed by four experienced optometrists in 175 eyes screened for refractive corneal or lens surgery for myopia or myopic astigmatism. Refraction was converted from sphere (SPH), cylinder (CYL) and axis to power vector components (spherical equivalent SEQ and cylinder projections C0 and C45). The mean power vectors of the three repeat measurements (MEAN) and the deviations (DEV) of the repeat measurements from the MEAN were evaluated. Results: MEAN values for SPH/CYL/SEQ/C0/C45 were −5.93/0.99/−5.44/−0.47/0.02 D and the corresponding standard deviations were 0.20/0.16/0.17/0.17/0.16 D. DEV of both SEQ and CYL correlated significantly with patient age (Spearman R = 0.16 and 0.20). DEV of CYL correlated with mean (myopic) SEQ (R = −0.22) and CYL (R = 0.27) whereas DEV of SEQ showed no significant correlation with mean SEQ or CYL. Conclusions: The variation in subjective manifest refraction with repeat measurements is in a range of ±0.16 to ±0.20 D for SPH, CYL and the power vector components SEQ, C0 and C45. If reliable subjective refraction measurements are mandatory, e.g., for planning refractive surgery procedures or for formula constant optimisation, repeat refractometry measures could help to ensure representative data and to estimate the intraindividual variations.

Diagnostics doi: 10.3390/diagnostics16091395

Authors: Maria Simona Dămășaru Eugen Bud Sorana Maria Bucur Mariana Păcurar Manuela Chibelean Silvia-Izabella Pop Alexandru Ștefan Zalana Irina Elena Muntean Lucian Cristian Petcu Mariana Cornelia Tilinca

Background: Chronological age does not always accurately reflect biological maturation in children, particularly in the presence of systemic conditions. Dental age is widely used as a biological maturity indicator; however, the impact of Type 1 diabetes mellitus on dental development remains unclear and inconsistently reported. Objective: This paper aims to explore differences between dental age (DA) and chronological age (CA) in children with Type 1 diabetes compared to healthy controls, and to assess the association between glycemic control (HbA1c) and dental maturation. Materials and Methods: This observational comparative study included 90 children aged 8–15 years: 45 with Type 1 diabetes and 45 age- and sex-matched healthy controls. Dental age was estimated using the Demirjian method and compared with chronological age. Group comparisons were performed using independent t-tests, while paired t-tests assessed within-group differences. Linear regression analysis evaluated the association between HbA1c and dental age. Effect sizes and 95% confidence intervals were reported. Results: In the diabetes group, dental age was significantly higher than chronological age (mean difference = 1.56 years, p < 0.001), indicating advanced dental maturation. No significant difference between dental and chronological age was observed in the control group. Dental age was also significantly higher in the diabetes group compared to controls (mean difference = 1.61 years, p < 0.001; Cohen’s d = 0.93). HbA1c levels were positively associated with dental age (R2 = 0.409, p < 0.01), suggesting that metabolic control may contribute to variability in dental maturation. Conclusions: Children with Type 1 diabetes appear to exhibit advanced dental maturation compared to healthy peers. Glycemic control may be associated with this variation, although the findings should be interpreted within the exploratory framework of the study. Dental age assessment should be used cautiously and in conjunction with other maturity indicators, particularly in children with systemic conditions.

Diagnostics doi: 10.3390/diagnostics16091394

Authors: Otto Scharff El-Nasser Helene Mens Nanna Skaarup Andersen Christoffer Valdemar Nissen Anne-Mette Lebech

Background/Objectives: Acrodermatitis chronica atrophicans (ACA), a late cutaneous manifestation of Lyme borreliosis, presents with a broad clinical spectrum. Most commonly, a characteristic bluish-red patchy rash, but it can also appear as unilateral limb swelling. This study aimed to characterize the clinical manifestations, diagnostic workup, and outcomes of patients with ACA in a tertiary setting in Denmark. Methods: Retrospective cohort study including all patients diagnosed with ACA at Copenhagen University Hospital-Rigshospitalet between 2017 and 2025. Results: Forty patients were included (median age 57 years; 63% female), with a median BMI of 24.5 [range 15.6–36.3]. Symptom duration was long (median 1 year). All patients presented with a skin rash. The most common location was the lower extremity, 26/40 (65%). Local edema and neuropathic pain were common (20/40) 50% and (23/40) 55%, respectively. A total of 13/40 patients underwent lymphoscintigraphy, which was deemed pathological in 7/13 (54%). The patients presenting with edema underwent significantly more imaging procedures, median 3 (range 1–5) vs. 0 (range 0–2), p < 0.005; they were younger, median age 49 years (range 17–76) vs. median 65 (range 30–81), p = 0.03; but did not differ in BMI, median 26.6 (range 19.0–36.2) versus median 23.8 (range 15.6–36.3), p = 0.48. All patients were Borrelia burgdorferi (Bb) IgG seropositive. Borrelia-specific PCR was positive in 6/13 (46%). Histopathology supported the diagnosis in 19/20 (95%). Clinical evaluation of the treatment response at 3 months was good in 33/40 (83%). Conclusions: Edema/swelling due to lymphatic obstruction is a common presentation of ACA in the tertiary setting, resulting in extensive diagnostic workup. The condition is associated with younger age but not BMI, sex, or immunodeficiency. Raised awareness and earlier testing for Bb IgG in serum seem warranted.

Diagnostics doi: 10.3390/diagnostics16091393

Authors: Haruo Miwa Ritsuko Oishi Nene Sakai Ryo Soma Kozue Shibasaki Yugo Ishino Shotaro Tsunoda Kazuki Endo Akihiro Funaoka Yuichi Suzuki Hiromi Tsuchiya Satoshi Komiyama Manabu Morimoto Shin Maeda

Background/Objectives: Transabdominal ultrasonography (TUS) is widely used for the detection of gallbladder lesions (GBLs), but differentiating malignant lesions from non-malignant lesions remains challenging. Microvascular flow imaging (MVFI), including superb microvascular imaging, detective flow imaging, and B-flow, enables visualization of low-flow vessels without contrast agents. This study aimed to characterize MVFI vascular features of GBLs and evaluate their reproducibility. Methods: We retrospectively analyzed 42 patients with GBLs who underwent TUS between March 2022 and December 2025. Two blinded readers independently assessed B-mode and MVFI findings. The evaluated MVFI findings included vascular flow detection, number of basal vessels, vessel shape, vessel thickness, and vessel irregularity. Interobserver agreement was assessed using Cohen’s kappa coefficient, and imaging findings were compared between invasive malignant and non-malignant lesions. Results: Of the 42 lesions, 10 were invasive malignant and 32 were non-malignant. Vascular signals were detected in all invasive malignant lesions and in 21 of 32 non-malignant lesions. Multiple basal vessels and vessel dilation were more frequently observed in invasive malignant lesions. Interobserver agreement was excellent for the number of basal vessels (κ = 0.91) and good for vessel thickness (κ = 0.72), indicating that these findings were more reproducible than other MVFI features. Conclusions: MVFI enables visualization of intralesional vascular features in GBLs. Multiple basal vessels and vessel dilation were associated with invasive malignancy and showed favorable reproducibility. These findings may serve as candidate imaging markers for future prospective validation.

Diagnostics doi: 10.3390/diagnostics16091392

Authors: Fedan Hacizade Mert Dogan Kudret Aytemir Ugur Canpolat

Background: Left bundle branch area pacing (LBBaP) has emerged as a physiological alternative to conventional biventricular pacing (BiVP) for cardiac resynchronization therapy (CRT). We aimed to compare long-term clinical, electrical, and echocardiographic outcomes of LBBaP versus BiVP in patients with heart failure with reduced ejection fraction (HFrEF). Methods: In this single-center retrospective study, 271 consecutive patients undergoing CRT implantation were included (LBBaP, n = 68; BiVP, n = 203). Outcomes included electrical resynchronization parameters, echocardiographic reverse remodeling, heart failure hospitalization, and all-cause mortality during a median follow-up of 41 months. Results: LBBaP achieved greater electrical resynchronization, with shorter postprocedural QRS duration (144 vs. 153 ms; p = 0.005) and shorter left ventricular activation time compared with BiVP. LBBaP was associated with lower radiation exposure (124 vs. 244 mGy; p < 0.001) and lower pacing thresholds. At 6 months, LVEF was higher in the LBBaP group (37.7% vs. 33.0%; p = 0.005), and heart failure hospitalization occurred less frequently (22.6% vs. 36.7%; p = 0.042). Long-term all-cause mortality did not differ between groups (p = 0.289). In multivariable analysis, baseline renal dysfunction and heart failure hospitalization within 6 months independently predicted mortality. Conclusions: In patients with HFrEF undergoing CRT, LBBaP provides superior electrical resynchronization and greater reverse remodeling compared with BiVP. Although associated with improved short-term clinical outcomes, long-term survival appears primarily determined by comorbid conditions rather than pacing modality.

Diagnostics doi: 10.3390/diagnostics16091391

Authors: Naohisa Yoshida Ken Inoue Reo Kobayashi Yoshikazu Inagaki Yuri Tomita Hikaru Hashimoto Yutaka Inada Ryohei Hirose Takeshi Yasuda Naoto Iwai Osamu Dohi Kazuhiko Uchiyama Hardesh Dhillon Tomohisa Takagi

Background and Objectives: Bowel bubble formation during colonoscopy can impair mucosal visualization and reduce procedural efficiency. However, its clinical significance remains incompletely characterized. This study aimed to evaluate the prevalence of severe bowel bubbles in the proximal colon and their impact on colonoscopic quality in patients undergoing bowel preparation with oral sulfate solution (OSS), using either a same-day regimen (SAR) with 480 mL OSS or a split-day regimen (SPR) with 960 mL OSS. Methods: This retrospective study was conducted between October 2024 and December 2025 across two affiliated institutions. Patients who underwent colonoscopy with OSS-based bowel preparation were included. SAR was used for screening, symptomatic evaluation, and surveillance colonoscopy. SPR was applied exclusively to patients with a prior history of sodium picosulfate-related abdominal pain or inadequate bowel preparation with SAR. Sodium picosulfate was prescribed on the day before colonoscopy in the SAR group and a low-residual diet was administered in both the SAR and SPR groups. The prevalence of severe bubbles in the proximal colon was evaluated, and their impact on colonoscopic quality was examined. Results: A total of 176 SAR cases and 51 SPR cases were analyzed. The rate of severe bubbles in the proximal colon was identical between both regimens (17.6%). Compared with cases without severe bubbles, those with severe bubbles had significantly longer cecal insertion times (median [IQR]: 7.0 [5.0–10.0] vs. 9.0 [7.0–13.0] min, p = 0.018) and total procedure time (20.0 [16.0–25.0] vs. 24.0 [19.0–30.0] min, p = 0.024). Preparation-to-colonoscopy time was also longer in cases with severe bubbles (5.0 [4.0–5.5] vs. 5.0 [5.0–6.0] h, p = 0.041). Adenoma detection rates were 73.2% in cases without severe bubbles and 67.5% in those with severe bubbles (p = 0.571). Conclusions: Severe bowel bubble formation tended to be associated with longer cecal insertion and total procedure times, and was more frequently observed with a longer preparation-to-colonoscopy interval.

Diagnostics doi: 10.3390/diagnostics16091389

Authors: Kun Wu Xiao Geng Xinguang Wang Jiazheng Chen Hua Tian

Background/Objectives: Coronal Plane Alignment of the Knee (CPAK) classification enables individualized alignment assessment in total knee arthroplasty (TKA), yet manual evaluation is time-consuming and lacks preoperative-to-postoperative transition analysis. Methods: This retrospective, single-center study aimed to develop and validate a fully automated deep learning-based CPAK classification system using internal validation on a held-out test set (n = 92) and to investigate individual-level transition patterns and their association with short-term clinical outcomes using paired radiographic data from a large Chinese cohort. A total of 919 KOA patients undergoing TKA were analyzed. A keypoint detection model (HRNet-W32) was developed to automatically calculate the medial proximal tibial angle, lateral distal femoral angle, arithmetic hip-knee-ankle angle, and joint line obliquity, from which CPAK types were derived. Results: On the validation set (92 cases), the model achieved a Mean Radial Error of 1.22 ± 0.43 mm for keypoint detection; mean absolute errors for MPTA and LDFA were ≤0.74°, while for aHKA and JLO they were 0.91° and 1.12°, respectively, with intraclass correlation coefficients ≥0.96 compared to manual annotations. Automatic CPAK classification accuracy was 80.98% (kappa = 0.767). Transition matrix analysis showed that only 9.36% of all patients maintained their original type postoperatively, with most shifting to types IV, V, or VII. After inverse probability weighting, no significant differences in clinical outcomes were observed among transition groups (all adjusted p > 0.05). Conclusions: These results demonstrate that the proposed automated system enables efficient CPAK assessment, revealing substantial postoperative alignment transitions that were not associated with differential short-term outcomes, thereby supporting AI-assisted individualized alignment planning in TKA.

Diagnostics doi: 10.3390/diagnostics16091390

Authors: Sena Aksoy Atay Vural İbrahim Kulaç Hatem Hakan Selçuk Ali Burak Kızılırmak Yasemin Gürsoy Özdemir Bayram Yılmaz

Background/Objectives: Mechanical thrombectomy (MT) enables direct examination of the retrieved thrombus in acute ischemic stroke. Thrombus composition may influence treatment outcomes and reflect underlying stroke mechanisms. This study aimed to analyze thrombus histological composition and CD34-positive endothelial cells and evaluate their association with clinical and radiological characteristics. Methods: Fifty-six patients with acute ischemic stroke who underwent MT were included. Thrombi were classified as fibrin-dominant or red blood cell (RBC)-dominant using hematoxylin–eosin staining (H&E). Endothelial cells were identified via CD34 immunostaining. Associations between thrombus composition, procedural variables, imaging findings, and clinical outcomes were analyzed. Results: Forty-one (73.2%) thrombi were fibrin-dominant, and 15 (26.8%) were RBC-dominant. Fibrin-dominant thrombi were significantly associated with more distal occlusions (p = 0.027) and with the use of stent-retrievers (p = 0.045). RBC-dominant thrombi were more frequently associated with the hyperdense artery sign (HAS) (p = 0.015). CD34-positive staining correlated with shorter symptom-to-door (p = 0.017) and symptom-to-puncture times (p < 0.001). Endothelial ingrowth was more common in thrombi from proximal occlusions (p = 0.017). No significant associations were observed between thrombus composition and recanalization success, number of passes, or functional outcomes. The association between RBC-dominant thrombi and HAS supports the potential role of imaging markers in predicting thrombus composition prior to intervention. In addition, the presence and distribution of CD34-positive endothelial cells in relation to time intervals and occlusion location may reflect dynamic processes such as thrombus organization and vessel wall interaction. Conclusions: These findings highlight the heterogeneous nature of thrombus in acute ischemic stroke. Further studies are needed to clarify the biological and clinical implications of these observations.

Diagnostics doi: 10.3390/diagnostics16091388

Authors: Pompiliu Mircea Bogdan Roxana Elena Bogdan-Goroftei Alina Plesea-Condratovici Adina Oana Armencia Letitia Doina Duceac Camer Salim Cristian Gutu Manuela Arbune Lavinia-Alexandra Moroianu Constantin Marinel Vlase Monica Mihaela Scutariu Alina Mihaela Calin

Background: Intensive care units (ICUs) provide management of critically ill patients requiring continuous monitoring and complex therapeutic interventions. The aim of this study was to analyze the clinical and biological characteristics associated with mortality in patients admitted to the intensive care unit. Methods: This retrospective observational study included 108 adult patients admitted to the Anesthesia and Intensive Care Unit of the “Sf. Apostol Andrei” Emergency County Clinical Hospital in Galați, who were in a coma at the time of admission. Demographic data, comorbidities, clinical parameters and biological biomarkers determined at admission were analyzed. Statistical analysis was performed using the SPSS program and included non-parametric tests (Mann–Whitney U), Spearman correlation analysis, multivariate logistic regression and ROC curve analysis to evaluate the predictive performance of biomarkers. Results: Hypertension (60.2%) and diabetes mellitus (35.2%) were the most common comorbidities. Comparative analysis revealed significant differences between deceased and surviving patients for several biological parameters, including leukocytes, C-reactive protein, LDH, D-dimers, INR and APTT. In multivariate analysis, LDH (OR = 0.998; p < 0.001) and APTT (OR = 0.951; p = 0.033) remained independently associated with mortality. ROC analysis revealed good discrimination capacity for LDH (AUC ≈ 0.805) and moderate performance for APTT. Conclusions: Determination of LDH and APTT at the time of admission to the ICU may provide useful information for assessing the prognosis of critically ill patients and for early stratification of mortality risk.

Diagnostics doi: 10.3390/diagnostics16091387

Authors: Alexandru Hamod Razvan Popovici Mihaela Oancea Mihaela Grigore Tudor Lazăr Ingrid-Andrada Vasilache Anda Pristavu Dumitru Gafițanu Alexandra Cristofor Adina Tănase Cristina Mandici Ana-Maria Grigore Liliana Strat Cristian Bucșineanu Manuela Ciocoiu

Background/Objectives: Emerging evidence links vaginal microbiome dysbiosis with HPV persistence and CIN progression, but whether microbiome markers provide incremental prognostic value beyond molecular triage assays remains unclear. This study aimed to evaluate whether Lactobacillus depletion and Shannon diversity improve prediction of biopsy-confirmed CIN2+ and CIN3+ outcomes beyond CINtec and HPV-16 genotyping. Methods: This was a secondary analysis of a cross-sectional study including 82 women undergoing cervical screening or follow-up for abnormal cytology. Associations with CIN2+, CIN3+, and CINtec positivity were estimated using modified Poisson regression. Multiplicative interaction between HPV-16 and Lactobacillus depletion was formally tested. Incremental discriminative performance was assessed using area under the receiver operating characteristic curve (AUC), DeLong’s test, net reclassification improvement (NRI), and integrated discrimination improvement (IDI). Results: HPV-16 was the strongest predictor of CIN2+ (PR = 6.08, p < 0.001) and CIN3+ (PR = 5.53, p = 0.001). A significant sub-multiplicative interaction indicated that Lactobacillus depletion carried its strongest prognostic signal in HPV-16-negative women (CIN3+: PR_interaction = 0.04, p = 0.003). Adding microbiome markers to CINtec + HPV-16 significantly improved CIN2+ discrimination (ΔAUC = 0.034, p = 0.031), driven by correct downward reclassification of non-events (NRI_non-events = 0.833). When added to HPV-16 + age, IDI for CIN2+ reached 0.092 (p = 0.004). Conclusions: Vaginal microbiome markers, particularly Lactobacillus depletion, provide statistically significant incremental discriminative value for CIN2+ beyond CINtec p16/Ki-67 dual staining and HPV-16 genotyping. Microbiome-based triage may be most impactful in HPV-16-negative women.

Diagnostics doi: 10.3390/diagnostics16091386

Authors: Yurie Nako Kiyotaka Kawai Shoko Katsumata Yuko Takayanagi Shogo Nishii Tatsuyuki Ogawa Makiko Tajima Osamu Hiraike

Background/Objectives: This study aimed to describe cumulative reproductive outcomes across three embryo transfer (ET) cycles after hysteroscopic endometrial polypectomy using a hysteroscopic tissue removal system (HTRS) and to identify determinants of cumulative and per-cycle pregnancy. Methods: In this single-center retrospective cohort study, we included infertile women who underwent HTRS-based endometrial polypectomy between January 2023 and December 2024 and subsequently initiated at least one ET cycle. Patients were followed from ET1 through ET3. The primary endpoint was the cumulative clinical pregnancy rate (CCPR) within three ET cycles. In the observed cumulative analysis, treatment discontinuation was considered as non-pregnancy. Kaplan–Meier (KM) analysis was used to estimate the cumulative pregnancy probability, with treatment discontinuation considered as censoring. Multivariate logistic regression and generalized estimating equations were used to identify patient-level and cycle-level predictors. Results: Among 100 patients, 79 achieved clinical pregnancy within three ET cycles (CCPR 79.0%). The KM estimate at ET3 was 87.4%, and the cumulative live birth rate was 65.0%. Pregnancy rates declined with advancing maternal age (≤34 years, 91.9%; 35–39 years, 78.3%; ≥40 years, 52.9%). Maternal age independently predicted lower cumulative pregnancy and lower per-cycle pregnancy probability, whereas blastocyst transfer was associated with a higher probability of pregnancy per cycle. Conclusions: In women who underwent ET after HTRS polypectomy, cumulative pregnancy across three ET cycles was relatively high; however progression to live birth declined with advancing maternal age. As no non-surgical comparison group was included, these findings should be interpreted as descriptive rather than causal.

Diagnostics doi: 10.3390/diagnostics16091385

Authors: Akiko Abe Yasushi Kotani Chiharu Wada Takaya Sakamoto Yoko Kashima Kosuke Murakami Hisamitsu Takaya Noriomi Matsumura

Background: Endoscopic sacrocolpopexy (ESC) is a widely performed procedure for pelvic organ prolapse, with laparoscopic sacrocolpopexy (LSC) and robotic-assisted sacrocolpopexy (RSC) approaches. However, suturing to the anterior longitudinal ligament at the sacral promontory carries a risk of massive hemorrhage due to presacral vascular injury. This study aimed to determine the frequency of presacral venous variations considered clinically relevant during suturing at the promontory and to explore their association with perioperative outcomes using contrast-enhanced three-dimensional computed tomography (3D-CT). Methods: Among 319 consecutive ESC cases performed between 2014 and 2025, 265 patients who underwent preoperative contrast-enhanced CT were retrospectively analyzed in this single-center cohort study. Two vascular findings were defined as clinically significant: (1) anomalous drainage of the internal iliac vein into the contralateral common iliac vein and (2) a clearly visualized median sacral vein on 3D reconstruction. The clinical impact of vascular abnormalities was evaluated using surgical time, blood loss, and perioperative complication rates as indicators. Student’s t-test was used for comparing continuous variables, and the chi-squared test was used for comparing categorical variables. The data for this study were retrospectively collected from electronic medical records, anonymized, and then analyzed. Results: Anomalous internal iliac vein drainage was observed in 11.3% (30/265), and a visible median sacral vein was observed in 10.2% (27/265). Overall, 17.7% (47/265, CI: 13.2–22.2%) of patients had at least one clinically significant variation. There were no significant differences between the groups in terms of age, parity, BMI, operative time, blood loss, or perioperative complication rates. No cases required transfusion. Conclusions: Clinically significant presacral vein mutations were present in approximately 1 in 6 patients. The main findings of this study are that clinically significant presacral vascular mutations are relatively frequent (17.7%) in ESC and that there was no significant difference in perioperative outcomes between patients with and without vascular mutations. Clinically relevant presacral vascular variations are relatively common in ESC. Preoperative contrast-enhanced 3D-CT may support risk assessment and surgical planning.