Diagnostics

21 pages, 1872 KB

Open AccessCase Report

Pregnancy-Associated Melanoma: A Molecular Reappraisal of the Hormonal Hypothesis, Illustrated by a Postpartum-Persistent Melanoma In Situ

by Laura Maghiar, Andrada Iftode, Andreea-Adriana Neamțu, Teodor-Andrei Maghiar, Raul Chioibas, Diana Haj-Ali, Cristina Dumitrescu, Ciprian-Nicușor Solomon, Valentin-Cristian Iovin, Ovidiu Tica, Anca Huniadi, Cristina-Adriana Dehelean and Ilarie Brihan

Diagnostics 2026, 16(15), 2485; https://doi.org/10.3390/diagnostics16152485 - 6 Aug 2026

Viewed by 389

Abstract

Background and Clinical Significance: Pregnancy-associated melanoma (PAM) is clinically challenging because the physiological pigmentary and naevus changes in pregnancy can obscure early malignancy, and the long-standing assumption that the hormonal milieu of pregnancy drives melanocytic transformation continues to shape clinical expectations. We [...] Read more.

Background and Clinical Significance: Pregnancy-associated melanoma (PAM) is clinically challenging because the physiological pigmentary and naevus changes in pregnancy can obscure early malignancy, and the long-standing assumption that the hormonal milieu of pregnancy drives melanocytic transformation continues to shape clinical expectations. We present a case of postpartum-persistent melanoma in situ and use it to anchor a molecular reappraisal of that hormonal hypothesis. Case Presentation: We describe the clinical, dermoscopic, histopathological, and immunohistochemical findings in a 32-year-old woman with a peri-umbilical naevus that changed during the third trimester and persisted twelve months postpartum, and we review the hormonal, immunological, and diagnostic literature relevant to PAM. Dermoscopy showed a multicomponent pattern with asymmetry, irregular structureless areas, peripheral pseudopods, and central regression; excisional biopsy demonstrated an atypical intraepidermal melanocytic proliferation without dermal invasion (melanoma in situ, pTis cN0 cM0, Stage 0), with Melan-A positivity and reduced p16. The reviewed evidence indicates that melanomas lack classical oestrogen/progesterone receptors and that the dominant oestrogen and α-MSH signals act through non-classical, differentiating pathways (GPER, MC1R) that are growth-suppressive rather than oncogenic, while pregnancy provides an immunologically permissive and diagnostically obscuring context. Conclusions: Pregnancy is better understood not as a hormonal driver of melanoma but as a permissive and obscuring state in which the principal preventable harm is diagnostic delay; suspicious lesions in pregnant or postpartum women warrant the same urgency as in other patients, and structured dermoscopic surveillance of at-risk women is the rational response. Full article

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

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15 pages, 271 KB

Open AccessArticle

Effects of Non-Surgical Periodontal Therapy on Gingival Crevicular Fluid Apelin Isoforms and Oxidative Stress Markers in Periodontitis

by Gozde Nur Aydogan, Hatice Yemenoglu, Oguz Kose, Semih Alperen Bostan, Sibel Mataraci Karakas and Adnan Yilmaz

Diagnostics 2026, 16(15), 2484; https://doi.org/10.3390/diagnostics16152484 - 6 Aug 2026

Viewed by 345

Abstract

Background/Objectives: Periodontitis is a chronic inflammatory disease in which host response and oxidative stress contribute to periodontal tissue destruction. Apelin isoforms may be involved in inflammatory regulation, tissue remodeling, and oxidative balance. This study evaluated changes in gingival crevicular fluid (GCF) apelin-13, apelin-36, [...] Read more.

Background/Objectives: Periodontitis is a chronic inflammatory disease in which host response and oxidative stress contribute to periodontal tissue destruction. Apelin isoforms may be involved in inflammatory regulation, tissue remodeling, and oxidative balance. This study evaluated changes in gingival crevicular fluid (GCF) apelin-13, apelin-36, total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) following non-surgical periodontal therapy (NSPT) in systemically healthy individuals with stage I–II or stage III–IV periodontitis. Methods: A total of 61 systemically healthy individuals with periodontitis were included and divided into two groups: stage I–II periodontitis (n = 31) and stage III–IV periodontitis (n = 30). Clinical periodontal parameters and GCF samples were obtained at baseline and at 1, 3, and 6 months after NSPT. Apelin-13 and apelin-36 levels were measured by enzyme-linked immunosorbent assay, while TAS and TOS levels were determined using commercial assay kits. OSI was calculated as the percentage ratio of TOS to TAS. The study was retrospectively registered at ClinicalTrials.gov (NCT06850987). Results: Baseline apelin-13 levels were significantly higher in stage III–IV periodontitis and decreased in both groups after NSPT, whereas apelin-36 increased over time and was higher in stage I–II periodontitis at baseline. Apelin-13 was positively associated with clinical periodontal parameters, while apelin-36 showed negative associations. TAS remained higher in stage I–II periodontitis, whereas OSI was consistently higher in stage III–IV periodontitis. Conclusions: These findings suggest that the combined assessment of GCF apelin isoforms and oxidative stress markers may provide useful biomarker information for distinguishing periodontitis severity and monitoring biochemical responses to NSPT. Full article

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

15 pages, 1313 KB

Open AccessArticle

Automated Diffusion-Weighted MRI Analysis for Exploratory Risk Stratification of Malignant Cerebral Edema After Acute Ischemic Stroke

by Cheng-Hsuan Juan, Chia-Hui Tsao, Ya-Hui Li, Chia-Ching Chang, Ming-Ting Tsai, Tung-Yang Lee, Cheng-En Juan, Hsiao-Wen Chung and Chun-Jung Juan

Diagnostics 2026, 16(15), 2483; https://doi.org/10.3390/diagnostics16152483 - 6 Aug 2026

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Abstract

Background/Objectives: Malignant cerebral edema (MCE) is an infrequent but devastating complication of acute ischemic stroke (AIS). Early, reliable identification of patients at risk remains a major clinical challenge. The purpose of this study was to evaluate SCR-U1.8, a single automated imaging biomarker integrating [...] Read more.

Background/Objectives: Malignant cerebral edema (MCE) is an infrequent but devastating complication of acute ischemic stroke (AIS). Early, reliable identification of patients at risk remains a major clinical challenge. The purpose of this study was to evaluate SCR-U1.8, a single automated imaging biomarker integrating stroke lesion burden and cerebrospinal fluid reserve, for exploratory risk stratification of MCE after AIS. Methods: In this retrospective study, consecutive patients with AIS who underwent diffusion-weighted imaging (DWI) between January 2019 and October 2022 were screened. Stroke lesions were automatically segmented on initial DWI using an ADC threshold of <1.8 × 10⁻³ mm²/s to derive U1.8 lesion volume. Cerebrospinal fluid volume (CSFV) was automatically estimated within the intracranial compartment, and SCR-U1.8 was calculated as U1.8/CSFV. Four low-complexity prediction strategies were evaluated: U1.8 > 82 mL, U1.8 > 145 mL, single-predictor U1.8 logistic regression, and single-predictor SCR-U1.8 logistic regression. Performance was evaluated across 100 repeated stratified patient-level train–test splits. Random undersampling was restricted to the training data, and no synthetic samples were generated. Model performance was assessed by accuracy, sensitivity, specificity, precision, negative predictive value (NPV), F1 score, receiver operating characteristic area under the curve (ROC-AUC), and average precision (AP) as appropriate. Results: A total of 530 patients were included, comprising 198 women and 332 men (mean age, 68 ± 14 years); a total of 12 patients developed MCE. Across 100 repeated stratified train–test splits, SCR-U1.8-LR achieved the highest accuracy (0.990 ± 0.006), precision (0.759 ± 0.150), specificity (0.992 ± 0.005), F1 score (0.806 ± 0.131), ROC-AUC (0.998 ± 0.002), and average precision (0.935 ± 0.062). Compared with the U1.8 > 82 mL threshold, SCR-U1.8-LR achieved significantly higher accuracy, precision, specificity, and F1 score, although sensitivity decreased from 1.000 to 0.900 and NPV decreased slightly from 1.000 to 0.998. Conclusions: SCR-U1.8 may provide a simple and physiologically interpretable measure of stroke lesion burden relative to CSF reserve. The findings remain exploratory because only 12 independent MCE events were available and require external validation. Full article

(This article belongs to the Special Issue Clinical Diagnostics and Management of Stroke)

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19 pages, 7765 KB

Open AccessArticle

Bowel Wall Vascularization in Crohn’s Disease: Exploratory Comparison of Vendor-Derived Vascular Index, ImageJ-Based Quantification, and Blinded Video-Based Doppler Scoring

by Paula Linhart, Wolfgang Kratzer, Mark Hänle, Jochen Klaus and Benedikt Haggenmüller

Diagnostics 2026, 16(15), 2482; https://doi.org/10.3390/diagnostics16152482 - 6 Aug 2026

Viewed by 306

Abstract

Background: Assessment of inflammatory activity in Crohn’s disease (CD) remains challenging. Bowel wall vascularization is an established marker of transmural inflammation and is typically evaluated using semiquantitative ultrasound scoring systems. In contrast, quantitative vascularization analysis is not yet widely used in clinical [...] Read more.

Background: Assessment of inflammatory activity in Crohn’s disease (CD) remains challenging. Bowel wall vascularization is an established marker of transmural inflammation and is typically evaluated using semiquantitative ultrasound scoring systems. In contrast, quantitative vascularization analysis is not yet widely used in clinical practice. To compare these approaches, this study evaluated semiquantitative and quantitative methods in the same patient cohort. Methods: This prospective single-center study included 50 patients with CD and sonographically detectable bowel wall thickening. Bowel wall vascularization was assessed using power Doppler (PD), color-coded superb microvascular imaging (cSMI) and monochrome mode superb microvascular imaging (mSMI). Video sequences were independently evaluated by three blinded readers using the Limberg classification. Quantitative vascularization was assessed using a vendor-derived vascular index and retrospective ImageJ analysis. Crohn’s Disease Activity Index (CDAI) and laboratory parameters were documented. Results: Interobserver agreement differed between imaging modalities. Krippendorff’s α values were 0.735 (PD), 0.655 (cSMI) and 0.527 (mSMI), indicating higher reliability for PD than for the SMI techniques. According to Fleiss’ κ (0.480 (PD), 0.376 (cSMI) and 0.367 (mSMI)), agreement was moderate for PD and fair for both SMI techniques. Complete concordance among all three readers was observed in 24 (PD), 18 (cSMI), and 22 (mSMI) patients, respectively. SMI-based techniques consistently resulted in higher Limberg grades compared to PD. Exploratory analyses showed strong correlations between different quantitative vascularization parameters (ρ up to 0.898, p < 0.001), but only moderate correlations with fecal calprotectin (FC) (ρ up to 0.389 with p = 0.017). Significant negative correlations were observed between vascular indices and body mass index (BMI) and skin-to-bowel distance (ρ up to −0.614, p < 0.001). The same trend was observed in the semiquantitative Limberg classification. Conclusions: Semiquantitative assessment of bowel wall vascularization seems to be limited by interobserver variability and Doppler technique, with SMI yielding higher Limberg grades than conventional Doppler. Standardized quantitative approaches may improve objectivity, but their reproducibility requires further validation. Patient-related factors should be considered when interpreting vascularization findings. Full article

(This article belongs to the Special Issue Advanced Ultrasound Techniques in Diagnosis, Second Edition)

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5 pages, 5548 KB

Open AccessInteresting Images

Anterior Chest Wall Pilonidal Sinus Mimicking Recurrent Abscess: Diagnostic Pitfalls and Therapeutic Implications

by Di Xu, Yimin He, Fangyi Wu, Jun Fu and Ying Gao

Diagnostics 2026, 16(15), 2481; https://doi.org/10.3390/diagnostics16152481 - 6 Aug 2026

Viewed by 258

Abstract

Pilonidal sinus is a chronic inflammatory skin condition predominantly found in the sacrococcygeal region, characterized by recurrent infections and sinus tract formation. Occurrences outside this area, particularly on the anterior chest wall, are exceedingly rare and prone to misdiagnosis. We report a rare [...] Read more.

Pilonidal sinus is a chronic inflammatory skin condition predominantly found in the sacrococcygeal region, characterized by recurrent infections and sinus tract formation. Occurrences outside this area, particularly on the anterior chest wall, are exceedingly rare and prone to misdiagnosis. We report a rare case of a 24-year-old Chinese man presenting with a 3-year history of a recurrent, draining lesion on the anterior chest wall. Initial treatment via simple incision and drainage for a presumed sebaceous cyst resulted in delayed wound healing and persistent purulent discharge. Subsequent magnetic resonance imaging (MRI) and computed tomography (CT) revealed a localized superficial lesion. Definitive surgical debridement uncovered a sinus tract containing embedded hair fragments. Histopathological examination confirmed a pilonidal sinus with a robust foreign body giant cell reaction and chronic inflammation. After complete resection, during the nearly two-year follow-up period, the healing has been smooth, and no recurrence has been observed. This case highlights the necessity of detailed clinical history-taking and the inclusion of ectopic pilonidal sinus in the differential diagnosis of refractory chest wall abscesses to prevent repeated, ineffective interventions. Full article

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

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16 pages, 2662 KB

Open AccessArticle

Clinical and Genetic Features in EYA1-Associated Branchio-Oto Syndrome: Cochlear Nerve Deficiency in Five of Thirteen Patients

by Yirong Niu, Yun Lin, Jiali Yu, Huanhuan Zhao, Yuting Zhao, Jie Chen, Ying Sun, Zeqi An, Mengping Wang, Kun Han, Hao Wu, Yun Li, Zhili Wang and Ying Chen

Diagnostics 2026, 16(15), 2480; https://doi.org/10.3390/diagnostics16152480 - 6 Aug 2026

Viewed by 355

Abstract

Background/Objectives: Branchio-oto syndrome (BOS) is an autosomal dominant disorder primarily associated with pathogenic variants in EYA1, mainly characterized by branchial anomalies, auricular abnormalities, and hearing loss. However, the co-occurrence of inner ear malformations in BOS remains understudied, especially severe malformations. This [...] Read more.

Background/Objectives: Branchio-oto syndrome (BOS) is an autosomal dominant disorder primarily associated with pathogenic variants in EYA1, mainly characterized by branchial anomalies, auricular abnormalities, and hearing loss. However, the co-occurrence of inner ear malformations in BOS remains understudied, especially severe malformations. This study aimed to investigate the clinical and genetic characteristics of patients with EYA1-associated BOS, with emphasis on cochlear nerve deficiency (CND). Methods: From January 2020 to April 2026, patients diagnosed with EYA1-associated BOS at an otology outpatient clinic in a tertiary hospital were included. Clinical manifestations, audiological assessments, imaging and genetic findings were analyzed. Results: Thirteen patients (six females and seven males) from eight unrelated families aged 0.3–58.3 years were enrolled. Branchial cleft fistulas and preauricular pits were each observed in 76.9% (10/13) of patients. The mean pure-tone average was 74.3 ± 20.7 dB HL. Eight EYA1 variants (four truncating, two large deletions, and two splicing) were identified. Among these, five were novel (c.320_329del, c.518del, c.1307dupT, c.1475+1G>A, and exon 12–18 deletion). CND was detected in 38.5% (5/13) of patients and 26.9% (7/26) of ears. Patients with CND carried either truncating variants (n = 3) or large deletions (n = 2) of EYA1. No CND was observed in patients with splicing variants. Conclusions: This study identifies five novel EYA1 pathogenic variants and suggests that CND may be a relatively common radiologic feature in EYA1-associated BOS, particularly among patients with truncating variants or large deletions, although larger studies are needed to confirm this association. Full article

(This article belongs to the Special Issue Recent Advances in Hearing and Audiology Science: Diagnosis and Management, 2nd Edition)

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18 pages, 2359 KB

Open AccessReview

Artificial Intelligence in the Assessment of Males with Chronic Pelvic Pain Syndrome: An Up-to-Date UPOINTS-Based Narrative Mapping Review

by Ali Talyshinskii, Fatima Kudakova, Olga Staroseltseva, Nariman Gadzhiev and Bhaskar Kumar Somani

Diagnostics 2026, 16(15), 2479; https://doi.org/10.3390/diagnostics16152479 - 6 Aug 2026

Viewed by 522

Abstract

Background/Objectives: Male chronic pelvic pain syndrome (CPPS) is a heterogeneous condition involving overlapping urinary, psychosocial, organ-specific, infectious, neurological, myofascial, and sexual phenotypes. This complexity limits the effectiveness of routine symptom assessment and empirical treatment strategies. Artificial intelligence (AI) may support more reproducible interpretation, [...] Read more.

Background/Objectives: Male chronic pelvic pain syndrome (CPPS) is a heterogeneous condition involving overlapping urinary, psychosocial, organ-specific, infectious, neurological, myofascial, and sexual phenotypes. This complexity limits the effectiveness of routine symptom assessment and empirical treatment strategies. Artificial intelligence (AI) may support more reproducible interpretation, differential diagnosis, phenotyping, and personalized management. This up-to-date narrative mapping review aimed to identify AI-assisted approaches that are directly or indirectly relevant to the assessment of males with CPPS, classify them according to UPOINTS phenotypic domains and clinical functions, and critically discuss the extent to which current evidence is disease-specific or extrapolated from related conditions. Methods: A literature search was performed in PubMed/MEDLINE, the Cochrane Library, and Google Scholar from database inception to May 2026 using terms related to male CPPS, UPOINTS domains, diagnosis, treatment, prognosis, digital solutions, artificial intelligence, machine learning, deep learning, natural language processing, computer vision, and decision support. Studies were included if they described AI-based or AI-adjacent computational approaches relevant to male CPPS or to related conditions important for UPOINTS-based phenotyping, differential diagnosis, or phenotype-specific assessment. Results: Available evidence remains fragmented and is largely extrapolated from related urological, chronic pain, pelvic floor, infectious, neurological, and sexual medicine conditions. AI applications were most developed in urinary and organ-specific domains, including uroflowmetry analysis, bladder volume assessment, cystoscopy, prostate imaging, urinary biomarkers, and differential diagnosis of lower urinary tract disorders. AI tools also showed potential for infection detection, psychosocial screening, chronic pain monitoring, neuroimaging-based phenotyping, pelvic floor dysfunction assessment, and evaluation of sexual dysfunction. However, male-CPPS-specific validation remains limited. Conclusions: AI has promising potential to improve differential diagnosis, multidomain phenotyping, and individualized management in males with CPPS. Current evidence is mainly translational and hypothesis-generating. Future studies should focus on prospective male-CPPS-specific cohorts, external validation, explainable multimodal models, and integration of AI tools into clinically meaningful, patient-centered workflows. Full article

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

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22 pages, 3763 KB

Open AccessReview

Artificial Intelligence for Integrated Analysis of Non-Blood Biological Fluids: From Biomarker Discovery to Clinical Decision-Support Systems

by Valentina Becherucci, Francesca Romano and Edda Russo

Diagnostics 2026, 16(15), 2478; https://doi.org/10.3390/diagnostics16152478 - 6 Aug 2026

Viewed by 357

Abstract

The analysis of non-blood biological fluids, including cerebrospinal fluid (CSF), serous effusions, and synovial fluid, plays a central role in laboratory medicine by providing essential diagnostic and prognostic information for neurological, infectious, inflammatory, and neoplastic diseases. However, the interpretation of these specimens remains [...] Read more.

The analysis of non-blood biological fluids, including cerebrospinal fluid (CSF), serous effusions, and synovial fluid, plays a central role in laboratory medicine by providing essential diagnostic and prognostic information for neurological, infectious, inflammatory, and neoplastic diseases. However, the interpretation of these specimens remains challenging because it requires the integration of heterogeneous biochemical, cytological, microbiological, molecular, and clinical data, often in the absence of standardized analytical workflows. Artificial intelligence (AI), particularly Machine Learning (ML) and Deep Learning (DL), is emerging as a powerful approach for extracting clinically relevant information from complex multidimensional datasets beyond the capabilities of conventional analytical methods. AI-driven Clinical Decision-Support Systems (CDSSs) can integrate laboratory findings with clinical, demographic, imaging, and multi-omics data, supporting diagnostic interpretation, patient stratification, and personalized clinical decision-making. At the same time, the convergence of AI with proteomics, metabolomics, metagenomics, and other omics technologies is accelerating biomarker discovery and advancing precision laboratory medicine. Current evidence indicates different levels of maturity across biological fluids. AI-assisted interpretation of CSF biomarkers and digital cytology of serous effusions currently show the strongest clinical evidence, whereas applications involving synovial fluid and integrated multi-omics remain largely exploratory. Although important technical, methodological, and regulatory challenges still limit widespread clinical implementation, AI has the potential to improve diagnostic accuracy, reduce interpretative variability, and support more integrated diagnostic workflows. This mini-review summarizes current and emerging AI applications in non-blood biological fluid analysis, with particular emphasis on biomarker discovery, CDSS, multi-omics integration, current evidence, existing limitations, and future perspectives for precision laboratory medicine. Full article

(This article belongs to the Special Issue From Innovation to Clinical Practice: Anticipating the New Era of AI-Driven Laboratory Medicine)

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19 pages, 2002 KB

Open AccessArticle

Intra- and Interobserver Reliability of the CT-Based Glenoid Arc-Angle Method Using Injured-Side and Contralateral Reference Circles: A Diagnostic Reliability Study

by Susanne Strasser, Johannes Dominikus Pallua, Anton Aschaber, Franz Kralinger, Dietmar Dammerer, Dietmar Krappinger, Rohit Arora and Clemens Hengg

Diagnostics 2026, 16(15), 2477; https://doi.org/10.3390/diagnostics16152477 - 6 Aug 2026

Viewed by 257

Abstract

Background/Objectives: This study aimed to compare the intraobserver and interobserver reliability and absolute agreement of the CT-based glenoid arc-angle method when the reference circle was constructed either directly on the injured glenoid or transferred from the healthy contralateral glenoid. The objective was [...] Read more.

Background/Objectives: This study aimed to compare the intraobserver and interobserver reliability and absolute agreement of the CT-based glenoid arc-angle method when the reference circle was constructed either directly on the injured glenoid or transferred from the healthy contralateral glenoid. The objective was to assess measurement reproducibility rather than anatomical validity, diagnostic accuracy, or clinical utility. Methods: Preoperative CT scans of 31 patients with anterior shoulder instability who underwent surgery were retrospectively analyzed. Three independent observers with different levels of experience performed measurements at two separate time points using two geometrical approaches. In the contralateral-reference method, the diameter of the best-fit circle was determined on the healthy contralateral glenoid and transferred to the injured side. In the injured-side method, the best-fit circle was determined directly on the injured glenoid. The defect angle and glenoid diameter were measured, and the defect angle was converted into an area-based percentage of glenoid bone loss. Intraobserver reliability was assessed across the two measurement sessions, whereas interobserver reliability was assessed across observer-specific means from the two sessions, using intraclass correlation coefficients with 95% confidence intervals. Absolute agreement, systematic bias, and measurement error between sessions were additionally evaluated using Bland–Altman analysis, the standard error of measurement, and the minimum detectable change. Results: The contralateral-reference method yielded numerically higher ICC point estimates for both measured parameters. For defect-angle measurements, the interobserver ICC based on observer-specific two-session mean estimates was 0.890 with the contralateral-reference method (95% CI: 0.811–0.942) and 0.603 with the injured-side method (95% CI: 0.399–0.767). For glenoid-diameter measurements, the corresponding interobserver ICCs were 0.900 (95% CI: 0.660–0.961) and 0.812 (95% CI: 0.672–0.900), respectively. Several confidence intervals crossed conventional reliability category boundaries and partially overlapped between methods; therefore, these findings represent numerical differences in point estimates rather than statistically established superiority. Conclusions: Within this cohort, the contralateral-reference method yielded numerically higher ICC point estimates, smaller session-related biases, and lower measurement-error estimates than the injured-side method. These descriptive findings do not establish statistically significant superiority, diagnostic accuracy, clinical utility, or treatment thresholds. The results are limited by the relatively small retrospective cohort of 31 surgically treated patients and the absence of anatomical or clinical outcome validation. Full article

(This article belongs to the Special Issue Interdisciplinary Approaches to Musculoskeletal Disorders: From Imaging to Management)

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12 pages, 1239 KB

Open AccessSystematic Review

Pancreatic Steatosis and Survival Outcomes in Pancreatic Ductal Adenocarcinoma: A Systematic Review of the Current Evidence

by Daniel Vasile Balaban, Manucu George and Mariana Jinga

Diagnostics 2026, 16(15), 2476; https://doi.org/10.3390/diagnostics16152476 - 6 Aug 2026

Viewed by 326

Abstract

Background: Pancreatic steatosis (PS) has emerged as a potential risk factor for pancreatic ductal adenocarcinoma (PDAC). While increasing evidence supports its role in pancreatic carcinogenesis, its prognostic significance after PDAC diagnosis remains unclear. We performed a systematic review to evaluate the association between [...] Read more.

Background: Pancreatic steatosis (PS) has emerged as a potential risk factor for pancreatic ductal adenocarcinoma (PDAC). While increasing evidence supports its role in pancreatic carcinogenesis, its prognostic significance after PDAC diagnosis remains unclear. We performed a systematic review to evaluate the association between PS and survival outcomes in patients with pancreatic cancer. Methods: A systematic search of PubMed and Scopus was conducted in May 2026 according to PRISMA guidelines. Observational studies assessing pancreatic steatosis by imaging or histology and reporting survival outcomes in PDAC patients were included. Risk of bias was evaluated using the Quality in Prognosis Studies (QUIPS) tool. Results: Five studies met inclusion criteria, comprising three imaging-based and two histology-based papers. Three studies reported findings suggestive of an adverse prognostic role of PS, whereas two found no significant association with survival. The strongest evidence originated from a study using quantitative histological assessment of pancreatic fat, which demonstrated that greater pancreatic fat accumulation was independently associated with poorer overall survival and recurrence-free survival following surgical resection. In contrast, imaging-based studies yielded inconsistent results. Histology-based studies consistently supported a negative prognostic impact, whereas CT-derived attenuation measures showed substantial variability. Risk of bias was moderate to high in most studies, largely due to retrospective designs, small sample sizes, heterogeneous definitions of pancreatic steatosis, and incomplete adjustment for metabolic confounders. Conclusions: Current evidence regarding the prognostic value of pancreatic steatosis in PDAC is limited and conflicting. While histology-based studies suggest an adverse impact on survival, imaging-based data remain inconsistent. Full article

(This article belongs to the Special Issue Diagnosis and Management of Pancreatic Cancer, Second Edition)

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11 pages, 1089 KB

Open AccessOpinion

Clinical Reasoning as the Guiding Framework in Medical Biochemical Test Reporting

by Torleif Trydal and Geir Erland Tjønnfjord

Diagnostics 2026, 16(15), 2475; https://doi.org/10.3390/diagnostics16152475 - 5 Aug 2026

Viewed by 286

Abstract

Clinical biochemical reports should reflect the clinical perspective, be well organized and biologically oriented, and present accurate reference values based on clinically relevant distributions. To illustrate possible quality issues, we selected Clinical Cases from The New England Journal of Medicine as it publishes [...] Read more.

Clinical biochemical reports should reflect the clinical perspective, be well organized and biologically oriented, and present accurate reference values based on clinically relevant distributions. To illustrate possible quality issues, we selected Clinical Cases from The New England Journal of Medicine as it publishes comprehensive reports to teach internationally relevant high-level workups. We evaluated their organization with a system organ grouping and the consistency of reference values between comparable cases. We found that the ordering of tests varied across issues, and associated interpretative tests were not organized in a scholarly manner. In several cases, the reference values for hemoglobin did not align with WHO recommendations, the upper reference value for glycohemoglobin did not correspond to established guidelines, and the upper reference value for creatinine did not reflect internationally standardized methods. The ferritin reference values in young women were not adjusted for the postmenopausal age group. When searching for incident blood loss using a common reference in young women and those of postmenopausal age in a large primary health care cohort, the frequency of flagged low ferritin results was so low that the ratio of flagged results to the incidence rate of colorectal cancer was only 1.1 (0.95 confidence interval 1.0 to 1.3). In men, low ferritin flagging was far more prevalent, resulting in a ratio of 11.7 (0.95 confidence interval 11.2 to 12.1). Thus, men had an 11-fold higher theoretical relative sensitivity when detecting occult iron loss compared with women. System organ assessment is a basic clinical competence, and system organ classification for clinical biochemical tests could be used to organize clinical laboratory reports. The reference values provided should be biologically based, harmonized, and readily recognizable by the clinician to accurately guide decisions, in contrast to local procedural determinations. Examination of local laboratory data may reveal biased laboratory support. Full article

(This article belongs to the Section Clinical Laboratory Medicine)

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11 pages, 974 KB

Open AccessArticle

The Diagnostic Value of Lung Ultrasound in Bronchopulmonary Dysplasia Among Preterm Infants with Gestational Age ≤ 28 Weeks

by Haifeng Zong, Bingchun Lin, Xueyu Chen, Yichu Huang, Jingyu Song, Hongyan Sun, Qingling Li, Sue Zhang and Chuanzhong Yang

Diagnostics 2026, 16(15), 2474; https://doi.org/10.3390/diagnostics16152474 - 5 Aug 2026

Viewed by 292

Abstract

Objective: The aim of this study was to explore the diagnostic value of lung ultrasound (LUS) for bronchopulmonary dysplasia (BPD) in extremely premature infants. Methods: This was a prospective observational cohort study in which infants with gestational age (GA) ≤ 28 [...] Read more.

Objective: The aim of this study was to explore the diagnostic value of lung ultrasound (LUS) for bronchopulmonary dysplasia (BPD) in extremely premature infants. Methods: This was a prospective observational cohort study in which infants with gestational age (GA) ≤ 28⁺⁶ weeks were included. LUS was performed at least once a week until 36 weeks of postmenstrual age. The LUS characteristics of infants with moderate–severe BPD were compared with those of infants with non–mild BPD. Results: A total of 114 infants were included, of which 69 (60.5%) had non–mild BPD, and 45 (39.5%) had moderate–severe BPD. The mean GA and birth weight of infants with non–mild BPD and moderate–severe BPD were 27.0 ± 1.4 and 26.3 ± 1.6 weeks and 969 ± 184 and 802 ± 228 g, respectively. The proportions of rough pleural lines, fused B-lines, patch-like anechoic appearance on the pleural surface, subpleural speckled hyperechoic appearance, lung consolidation (≥0.5 cm), fuzzy or invisible A-lines, and pleural insect erosion (PIE)-like changes in the moderate–severe BPD group were significantly greater than those in the non–mild BPD group (100% vs. 37.7%, 88.9% vs. 13.0%, 84.4% vs. 7.2%, 73.3% vs. 8.7%, 80.0% vs. 11.6%, 86.7% vs. 10.1%, and 75.6% vs. 5.8%, respectively; p < 0.001). In evaluating moderate–severe BPD, rough pleura had 100.0% (95% CI: 0.921–1.000) in sensitivity, 63.4% (95% CI: 0.518–0.736) in PPV, and 62.3% (95% CI: 0.505–0.728) in specificity. PIE-like changes had 75.6% (95% CI: 0.613–0.858) in sensitivity, 89.5% (95% CI: 0.759–0.958) in PPV, and 94.2% (95% CI: 0.860–0.977) in specificity. Pleura surface irregular patch-like anechoic had 84.4% (95% CI: 0.712–0.923) in sensitivity, 88.4% (95% CI: 0.755–0.949) in PPV, and 92.8% (95% CI: 0.841–0.969) in specificity. Subpleural speckled hyperechogenicity had 73.3% (95% CI: 0.592–0.840) in sensitivity, 84.6% (95% CI: 0.704–0.930) in PPV, and 91.3% (95% CI: 0.824–0.960) in specificity. Conclusions: LUS is a valuable tool for evaluating and diagnosing BPD. Full article

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

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19 pages, 2778 KB

Open AccessArticle

Early Prediction of Volumetric Progression in Sellar–Parasellar Meningiomas Using Delta Radiomics on 6-Month MRI Following Gamma Knife Radiosurgery

by Merve Yazol, Halil Özer, Pelin Kuzucu and Burak Karaaslan

Diagnostics 2026, 16(15), 2473; https://doi.org/10.3390/diagnostics16152473 - 5 Aug 2026

Viewed by 325

Abstract

Background/Objectives: This study aimed to develop and internally validate multiparametric MRI radiomics models for predicting volumetric progression following Gamma Knife radiosurgery (GKRS) in sellar–parasellar meningiomas and to evaluate the incremental value of diffusion-derived features beyond contrast-enhanced imaging. Methods: Fifty-four patients underwent [...] Read more.

Background/Objectives: This study aimed to develop and internally validate multiparametric MRI radiomics models for predicting volumetric progression following Gamma Knife radiosurgery (GKRS) in sellar–parasellar meningiomas and to evaluate the incremental value of diffusion-derived features beyond contrast-enhanced imaging. Methods: Fifty-four patients underwent pretreatment and approximately 6-month post-treatment MRI, including contrast-enhanced T1-weighted imaging (T1C-WI) and apparent diffusion coefficient (ADC) maps. Whole-tumor segmentations were reviewed by two neuroradiologists by consensus. Radiomic features were extracted using PyRadiomics, and delta features were calculated as post-treatment minus pretreatment values. Elastic-net logistic regression models were evaluated using repeated nested cross-validation with five-fold inner and outer loops repeated 10 times. The primary endpoint was volumetric progression, defined as a >20% volume increase at 3 years. Results: At 3 years, 9 tumors (16.7%) progressed, 25 (46.3%) remained stable, and 20 (37.0%) regressed. The ΔT1C-WI model showed the highest repeated nested cross-validation performance, with a mean AUC of 0.861 ± 0.065, an accuracy of 0.846 ± 0.037, and an F1 score of 0.579 ± 0.097. Averaged patient-level out-of-fold predictions yielded an AUC of 0.914 (95% CI, 0.822–0.980), a sensitivity of 77.8%, and a specificity of 88.9%. The ΔADC model showed moderate discrimination, whereas combining ΔT1C-WI and ΔADC features did not improve performance. Conclusions: Delta radiomics derived from 6-month post-treatment T1C-WI may help identify sellar–parasellar meningiomas at risk of 3-year volumetric progression after GKRS. These findings suggest that 6-month ΔT1C-WI radiomics may support early risk stratification, but its clinical value requires external validation and prospective evaluation. Full article

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

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3 pages, 156 KB

Open AccessReply

Reply to Kiral, B.S. Ultrasonographic Evaluation of Superior Cluneal Nerve Entrapment: Methodological Considerations. Comment on “Iudicelli et al. The Role of Musculoskeletal Ultrasound in Detecting Superior Cluneal Nerve Entrapment: Biomechanical Insights in Chronic Low Back Pain—A Pilot Study. Diagnostics 2026, 16, 469”

by Giovanni Iudicelli, Francesco Agostini, Alberto Altarocca, Francesco Ioppolo, Marco Narciso, Marco Conti, Andrea Fisicaro, Alessio Savina, Vincenzo Di Nunno, Massimiliano Mangone, Stefano Galletti and Marco Paoloni

Diagnostics 2026, 16(15), 2472; https://doi.org/10.3390/diagnostics16152472 - 5 Aug 2026

Viewed by 239

Abstract

We thank Dr. Kiral for a thoughtful and constructive commentary, with which we largely agree. Surrogate biomechanical markers and direct visualisation of the SCN are complementary rather than competing: the markers were intended to extend diagnostic support to the many settings and patients [...] Read more.

We thank Dr. Kiral for a thoughtful and constructive commentary, with which we largely agree. Surrogate biomechanical markers and direct visualisation of the SCN are complementary rather than competing: the markers were intended to extend diagnostic support to the many settings and patients in whom direct visualisation is not easy to achieve, whether for patient-related reasons or because high-resolution equipment and dedicated expertise are not universally available. We agree that these findings are supportive rather than primary diagnostic markers, and that their value may lie in the triad within a clinically pre-selected population rather than in any single sign. The nociceptive–neuropathic distinction the author emphasises is itself one of the central conclusions of our study. Full article

(This article belongs to the Special Issue Musculoskeletal Disorders: Diagnosis, Management, and Rehabilitation, 2nd Edition)

4 pages, 556 KB

Open AccessComment

Ultrasonographic Evaluation of Superior Cluneal Nerve Entrapment: Methodological Considerations. Comment on Iudicelli et al. The Role of Musculoskeletal Ultrasound in Detecting Superior Cluneal Nerve Entrapment: Biomechanical Insights in Chronic Low Back Pain—A Pilot Study. Diagnostics 2026, 16, 469

by Busra Sezer Kiral

Diagnostics 2026, 16(15), 2471; https://doi.org/10.3390/diagnostics16152471 - 5 Aug 2026

Cited by 1 | Viewed by 494

Abstract

Superior cluneal nerve (SCN) entrapment is an underrecognized cause of chronic low back pain, and musculoskeletal ultrasound has recently gained attention as a potential diagnostic tool. In a recent pilot study, an indirect ultrasonographic triad consisting of thoracolumbar fascia thickening, iliac crest enthesophytes, [...] Read more.

Superior cluneal nerve (SCN) entrapment is an underrecognized cause of chronic low back pain, and musculoskeletal ultrasound has recently gained attention as a potential diagnostic tool. In a recent pilot study, an indirect ultrasonographic triad consisting of thoracolumbar fascia thickening, iliac crest enthesophytes, and Copeman nodules was proposed as a potential diagnostic indicator of SCN entrapment. In this comment, we discuss several anatomical and methodological considerations regarding the ultrasonographic evaluation of SCN entrapment. Based on previous anatomical studies and our own ultrasonographic experience, we emphasize that the principal role of ultrasonography in SCN entrapment is to facilitate accurate ultrasound-guided diagnostic nerve blocks by identifying the target anatomy. Although direct visualization of the SCN may provide supportive anatomical information, the diagnosis should remain based on the clinical presentation and, when indicated, confirmation by an ultrasound-guided diagnostic nerve block. Further multicenter prospective studies are needed to establish standardized ultrasonographic diagnostic criteria for SCN entrapment. Full article

(This article belongs to the Special Issue Musculoskeletal Disorders: Diagnosis, Management, and Rehabilitation, 2nd Edition)

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5 pages, 5899 KB

Open AccessInteresting Images

Intestinal Endometriosis in a 38-Year-Old Woman

by Ruoxi Zhang, Xiaoqing Li, Aiming Yang and Qiang Wang

Diagnostics 2026, 16(15), 2470; https://doi.org/10.3390/diagnostics16152470 - 5 Aug 2026

Viewed by 302

Abstract

Endometriosis is a common gynecological disorder that can involve the intestinal tract and may present with bleeding, bowel obstruction, and, rarely, perforation or malignant transformation. Intestinal endometriosis can mimic malignant tumors or other conditions, which may lead to unnecessary aggressive surgical resections. It [...] Read more.

Endometriosis is a common gynecological disorder that can involve the intestinal tract and may present with bleeding, bowel obstruction, and, rarely, perforation or malignant transformation. Intestinal endometriosis can mimic malignant tumors or other conditions, which may lead to unnecessary aggressive surgical resections. It continues to be a challenging diagnosis to make preoperatively. We report a case of intestinal endometriosis with endoscopic features of lymphatic dilatation-like changes, which correlated with the pathological findings, aiming to provide a reference for the endoscopic recognition of intestinal endometriosis. Full article

(This article belongs to the Special Issue Complex Digestive Diseases: Diagnosis and Management)

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19 pages, 1788 KB

Open AccessArticle

Inflammatory–Hematological Profiles in Nasopharyngeal Carcinoma and Suspicious Adenoid Hypertrophy: An Exploratory Single-Center Study

by Darius Radu Roman, Carmen Delia Nistor-Cseppento, Dana Carmen Zaha, Timea Claudia Ghitea, Alexia Manole, Dana Zdremtan, Alexandru Chioreanu, Daniela Florina Trifan, Palade Octavian Dragoș and Felicia Manole

Diagnostics 2026, 16(15), 2469; https://doi.org/10.3390/diagnostics16152469 - 5 Aug 2026

Viewed by 353

Abstract

Background: Differentiating nasopharyngeal carcinoma (NPC) from benign nasopharyngeal lesions may be challenging because clinical and endoscopic findings can overlap. This study compared routine inflammatory and hematological biomarkers between patients with histopathologically confirmed NPC and patients with suspicious but histopathologically benign adenoid hypertrophy [...] Read more.

Background: Differentiating nasopharyngeal carcinoma (NPC) from benign nasopharyngeal lesions may be challenging because clinical and endoscopic findings can overlap. This study compared routine inflammatory and hematological biomarkers between patients with histopathologically confirmed NPC and patients with suspicious but histopathologically benign adenoid hypertrophy (AH). Methods: This retrospective single-center study included 72 adults evaluated between January 2024 and January 2026: 36 patients with NPC and 36 with AH. Routine hematological and inflammatory variables were compared between groups. After inconsistencies were identified in the originally derived indices, the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) were recalculated using the available absolute blood-cell-count variables. Receiver operating characteristic analyses and exploratory Firth penalized logistic regression were performed, with histopathologically confirmed NPC coded as the positive outcome. Results: Patients with NPC were younger than patients with AH (38.14 ± 7.64 vs. 56.06 ± 8.29 years; p < 0.001). CRP, ESR, and leukocyte count were significantly higher in the NPC group. PLR was significantly higher in the AH group, whereas NLR and SII did not differ significantly between groups. CRP demonstrated apparent complete discrimination between the two selected diagnostic groups (AUC 1.000), while ESR yielded an AUC of 0.948. In the Firth penalized logistic regression model adjusted for age, sex, and smoking status, each 10 mg/L increase in CRP was associated with higher odds of NPC (adjusted OR 3.16, 95% CI 1.68–16.72; p < 0.001). The addition of CRP increased the model AUC from 0.950 to 1.000. Conclusions: Routine inflammatory markers showed different cross-sectional distributions between patients with node-positive NPC and patients with suspicious benign adenoid hypertrophy. CRP provided incremental discriminatory information in this selected cohort but should not be interpreted as a validated stand-alone diagnostic marker. The findings require prospective external validation in a larger and clinically representative population. Full article

(This article belongs to the Section Clinical Laboratory Medicine)

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16 pages, 5618 KB

Open AccessSystematic Review

Artificial Intelligence for Diagnosis of Temporomandibular and Cranio-Cervico-Mandibular Musculoskeletal Disorders: A Systematic Review and Exploratory Diagnostic Test Accuracy Meta-Analysis

by Arturo Arbeláez Ramírez and Daniel Botero Rosas

Diagnostics 2026, 16(15), 2468; https://doi.org/10.3390/diagnostics16152468 - 5 Aug 2026

Viewed by 385

Abstract

Objectives: To systematically evaluate the diagnostic accuracy, clinical applicability, and methodological maturity of artificial intelligence (AI)-based methods for temporomandibular disorders (TMD), temporomandibular joint (TMJ) abnormalities, and related cranio-cervico-mandibular (CCM) musculoskeletal conditions compared with conventional diagnostic methods and accepted reference standards. Materials and [...] Read more.

Objectives: To systematically evaluate the diagnostic accuracy, clinical applicability, and methodological maturity of artificial intelligence (AI)-based methods for temporomandibular disorders (TMD), temporomandibular joint (TMJ) abnormalities, and related cranio-cervico-mandibular (CCM) musculoskeletal conditions compared with conventional diagnostic methods and accepted reference standards. Materials and Methods: This systematic review and exploratory diagnostic test accuracy meta-analysis was conducted in accordance with PRISMA 2020 and PRISMA-DTA. The protocol was retrospectively registered in PROSPERO (CRD420261428138). PubMed/MEDLINE, Embase, and Scopus were searched from database inception through February 2026. Eligibility for the primary synthesis was restricted to published studies in English or Spanish involving adults aged 18 years or older. All extracted records were re-audited article by article to align the evidence with the diagnostic question. The domain-specific quantitative synthesis was restricted to TMJ osteoarthritis studies with explicit 2 × 2 diagnostic data or a unique, verifiable reconstruction from reported class totals and sensitivity/specificity. Risk of bias was assessed with QUADAS-2. Results: From 1471 records identified, 174 entered the master extraction dataset. After reclassification, 84 records were retained for primary TMD/TMJ qualitative synthesis, 8 as secondary CCM musculoskeletal evidence, 31 as conventional or reference standard supporting evidence, 33 as methodological or contextual evidence, 4 as differential orofacial pain evidence, and 14 as excluded or minimal-background records. Twenty-one studies were assessed as potential diagnostic accuracy candidates. Three TMJ osteoarthritis studies contributed to the domain-specific exploratory meta-analysis: two with explicit 2 × 2 data and one with a reproducible reconstruction. Pooled sensitivity was 0.791 (95% CI: 0.700–0.861) and pooled specificity was 0.869 (95% CI: 0.811–0.911). Heterogeneity was substantial for sensitivity (I² = 68.2%) and moderate for specificity (I² = 57.3%). Conclusions: AI demonstrates promising performance in selected image-based TMJ osteoarthritis tasks. Nevertheless, the evidence remains exploratory because only three studies were quantitatively comparable, one table was reconstructed, and modalities and validation designs differed. AI should be interpreted as an augmentative decision support tool rather than a replacement for MRI, CBCT, or validated clinical frameworks such as DC/TMD. Clinical Relevance: AI may support image-based TMD/TMJ workflows, but present evidence does not justify autonomous diagnosis or replacement of established clinical and imaging reference standards. Full article

(This article belongs to the Special Issue Advances in Dental Diagnostics)

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12 pages, 360 KB

Open AccessArticle

Effective Dose Evaluation of Cerebral Angiography Using Kerma Area Product and Development of Effective Dose Conversion Factors

by Jeongbok Min and Jungsu Kim

Diagnostics 2026, 16(15), 2467; https://doi.org/10.3390/diagnostics16152467 - 5 Aug 2026

Viewed by 272

Abstract

Background/Objectives: Transfemoral cerebral angiography (TFCA) involves significant radiation exposure because of prolonged fluoroscopy and repeated imaging sequences. Because complex dose simulations are often infeasible in routine clinical practice, this study employed PC-based Monte Carlo methods to estimate organ-absorbed and effective doses. The [...] Read more.

Background/Objectives: Transfemoral cerebral angiography (TFCA) involves significant radiation exposure because of prolonged fluoroscopy and repeated imaging sequences. Because complex dose simulations are often infeasible in routine clinical practice, this study employed PC-based Monte Carlo methods to estimate organ-absorbed and effective doses. The primary objective was to establish Kerma area product (KAP)-based conversion factors to facilitate efficient clinical dose assessment. Methods: We analyzed 30 patients who underwent TFCA. Key parameters, including total KAP, tube voltage, and projection angles, were obtained from DICOM Radiation Dose Structured Reports. Monte Carlo simulations were conducted for anteroposterior, lateral, and cranial planes. The conversion factors were then derived by calculating the ratio of the effective dose to the total KAP. Results: The average KAP was 36.23 ± 6.81 Gy·cm². Effective doses calculated via Monte Carlo simulation were 1.70 ± 0.35 mSv under International Commission on Radiological Protection (ICRP) 60 and 1.90 ± 0.40 mSv under ICRP 103 standards. The corresponding conversion factors were 0.0468 ± 0.0054 and 0.0525 ± 0.0065 mSv/Gy·cm² respectively. Notably, the ICRP 103-based factor was 12.2 percent higher than the ICRP 60-based factor, reflecting updated tissue weighting factors in modern dosimetry. Conclusions: This study provides standardized conversion factors that allow rapid and reliable dose estimation without requiring complex simulations. The findings demonstrated substantial radiation absorption in the head and neck regions, providing critical data for routine dose monitoring. These results emphasize the importance of rigorous radiation protection and safety protocols during interventional procedures. Full article

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

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17 pages, 429 KB

Open AccessSystematic Review

Reported Prevalence of Inherited Thrombophilia in Pregnancy: Impact of Cohort Selection on Screening Implications—A Systematic Review

by Maria Fulina, Lucian Șerbănescu, Georgeta-Camelia Cozaru, Elena Danteș, Elena Dumea, Eugenia-Alina Radu and Elena Mocanu

Diagnostics 2026, 16(15), 2466; https://doi.org/10.3390/diagnostics16152466 - 5 Aug 2026

Viewed by 336

Abstract

Background/Objectives: Inherited thrombophilia (IT) has been extensively investigated as a potential contributor to adverse pregnancy outcomes; however, reported prevalence varies widely across studies. This systematic review aimed to evaluate how cohort selection influences the reported prevalence of inherited thrombophilia in pregnancy and [...] Read more.

Background/Objectives: Inherited thrombophilia (IT) has been extensively investigated as a potential contributor to adverse pregnancy outcomes; however, reported prevalence varies widely across studies. This systematic review aimed to evaluate how cohort selection influences the reported prevalence of inherited thrombophilia in pregnancy and to explore the implications of this variability for clinical interpretation and screening practices. Methods: A systematic review was conducted following PRISMA 2020 guidelines. PubMed, Scopus, Web of Science, and Google Scholar were searched. A total of 5480 records were identified, and 7 observational studies (cohort and case–control) met inclusion criteria. Data were synthesized qualitatively due to heterogeneity. Results: Prevalence ranged from 0% to 14%, depending on population characteristics. The largest cohort study reported an inherited thrombophilia prevalence of 8.1%, comparable to the general population. Higher rates were observed in referral-based and antiphospholipid Syndrome (APS)-associated cohorts, while case–control studies showed no significant differences between affected individuals and controls. Ethnic variability was also observed. Conclusions: These findings should be interpreted as patterns observed across heterogeneous study designs rather than as definitive evidence of causality. Current evidence does not clearly support universal screening in pregnancy; however, the findings should be interpreted cautiously because several included studies were limited by small sample sizes and methodological heterogeneity. Full article

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

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12 pages, 16126 KB

Open AccessArticle

Evaluation of High-Risk Anatomical Features in Single and Opposite-Sinus Origin Coronary Artery Anomalies Using Coronary Computed Tomography Angiography

by Fatma Durmaz and Ebru Temel Kurt

Diagnostics 2026, 16(15), 2465; https://doi.org/10.3390/diagnostics16152465 - 5 Aug 2026

Viewed by 327

Abstract

Objective: To characterize the anatomical spectrum of a single coronary artery (SCA) and an anomalous coronary artery originating from the opposite sinus of Valsalva (ACAOS) and to assess high-risk features using Coronary computed tomography angiography (CCTA)-based quantitative parameters. Methods: A retrospective [...] Read more.

Objective: To characterize the anatomical spectrum of a single coronary artery (SCA) and an anomalous coronary artery originating from the opposite sinus of Valsalva (ACAOS) and to assess high-risk features using Coronary computed tomography angiography (CCTA)-based quantitative parameters. Methods: A retrospective review of 2513 consecutive CCTA examinations performed between June 2021 and December 2025 was conducted. Patients diagnosed with ACAOS or SCA were included. Coronary origin, course patterns, and morphological characteristics were analyzed. High-risk features—including interarterial course, intramural segment, acute take-off angle, slit-like ostium, intramural length, and interluminal space (ILS)—were quantitatively assessed using multiplanar and curved MPRs. Results: Twenty-two patients (0.88%) were identified (ACAOS: 0.64%, n = 16; SCA: 0.24%, n = 6). All SCA cases showed benign courses. Among ACAOS patients, 62.5% had an interarterial course. In this subgroup, the mean take-off angle was 14.4° ± 4.5°, with universal slit-like ostium and intramural course. Mean intramural length was 9.21 ± 2.00 mm and minimal ILS was 0.87 ± 0.12 mm. Conclusions: CCTA enables comprehensive anatomical characterization of morphological features associated with higher risk in patients with ACAOS and SCA. Quantitative assessment of parameters such as the take-off angle, intramural course, slit-like ostium, intramural length, and interluminal space may complement clinical evaluation, although further prospective studies incorporating functional ischemia assessment and clinical outcome data are needed to clarify their clinical significance. Full article

(This article belongs to the Special Issue Advancements in Cardiovascular Imaging)

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13 pages, 17781 KB

Open AccessCase Report

Two Cases of Steroid Cell Tumour, Not Otherwise Specified, of the Ovary with Distinct Exon 3 CTNNB1 Hotspot Mutations (p.D32V and p.S45P): Further Evidence of Wnt/β-Catenin-Pathway Involvement

by Sarah Bouri, Philomène Lavis and Jean-Christophe Noël

Diagnostics 2026, 16(15), 2464; https://doi.org/10.3390/diagnostics16152464 - 5 Aug 2026

Viewed by 280

Abstract

Background and Clinical Significance: Steroid cell tumours of the ovary, not otherwise specified (SCT-NOSs), are rare sex cord–stromal neoplasms with a poorly characterised molecular landscape, in which only exceptional CTNNB1 mutations have so far been reported and no recurrent driver alteration is firmly [...] Read more.

Background and Clinical Significance: Steroid cell tumours of the ovary, not otherwise specified (SCT-NOSs), are rare sex cord–stromal neoplasms with a poorly characterised molecular landscape, in which only exceptional CTNNB1 mutations have so far been reported and no recurrent driver alteration is firmly established. A better characterisation of their molecular spectrum has clinical significance for accurate diagnostic categorisation of ovarian sex cord–stromal tumours and for the identification of potentially targetable pathway alterations in this rare entity. Case Presentation: We report two consecutive SCT-NOSs of the right ovary, retrieved from the archives of the Department of Pathology of the Hôpital Universitaire de Bruxelles and of Curepath. Both underwent comprehensive sex cord–stromal and differential immunohistochemistry and targeted next-generation sequencing on a 168-gene panel with a mean coverage of 2690× (Case 1) and a 17-gene panel (Case 2) (MGI DNBSEQ-T7 for Case 1; Ion GeneStudio S5 for Case 2). A 56-year-old post-menopausal woman (Case 1) and a 50-year-old immunosuppressed woman with a history of renal transplantation and lymphoma (Case 2) both presented with rapidly progressive virilisation. The two right ovarian tumours (20 to 25 mm, no Reinke crystals) displayed an unambiguous sex cord–stromal immunophenotype (α-inhibin, calretinin, SF-1 and Melan-A positive; CD10, WT1, EMA, AE1/AE3 and PAX8 negative), with aberrant nuclear and cytoplasmic β-catenin staining. Sequencing identified a pathogenic CTNNB1 c.133T>C p.(Ser45Pro) variant in Case 1 and a pathogenic CTNNB1 c.95A>T p.(Asp32Val) variant in Case 2, with wild-type FOXL2 in both. Conclusions: Three of the four molecularly characterised CTNNB1-mutated SCT-NOSs converge on the two principal GSK-3β phosphorylation residues of β-catenin, identifying Wnt/β-catenin-pathway dysregulation as a potentially recurrent event and providing additional evidence for the involvement of the Wnt/β-catenin pathway in an emerging molecular subset of SCT-NOS. In a tumour with the canonical sex cord–stromal immunophenotype, an exon 3 CTNNB1 hotspot mutation should not be regarded as evidence against the diagnosis of SCT-NOS and may help define a distinct molecular subset. Full article

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

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13 pages, 619 KB

Open AccessArticle

Lactate Clearance as a Prognostic Marker in Severe Trauma: A Retrospective Cohort Study

by Lotfi Rebai, Melinda Sammary, Olfa Faten, Sabrine Ben Brahem, Firas Kalai, Ichraf Ardhaoui and Lamia Thabet

Diagnostics 2026, 16(15), 2463; https://doi.org/10.3390/diagnostics16152463 - 5 Aug 2026

Viewed by 367

Abstract

Background/Objectives: Lactate is a key biomarker of tissue hypoperfusion in severe trauma. While admission lactate is widely used, the prognostic value of delayed lactate clearance remains a subject of ongoing investigation, notably due to the inherent risk of survivorship bias. This study [...] Read more.

Background/Objectives: Lactate is a key biomarker of tissue hypoperfusion in severe trauma. While admission lactate is widely used, the prognostic value of delayed lactate clearance remains a subject of ongoing investigation, notably due to the inherent risk of survivorship bias. This study assessed the association between lactate kinetics and in-hospital mortality in a cohort of severely injured patients admitted to the intensive care unit. Methods: We conducted a single-center retrospective cohort study including adult patients (≥18 years) admitted to the ICU for severe trauma between January 2018 and December 2022. Arterial lactate was measured at H0, H4 (±1 h), and H12 (±1 h). Lactate clearance (LC) was calculated using the formula: LC (%/h) = [(Lactate_t1 − Lactate_t2)/Lactate_t1] × (1/Δt) × 100, where positive values indicate decreasing lactate (clearance) and negative values indicate worsening lactatemia. LC was calculated over H0–H4, H0–H12, and H4–H12. Among the 38 patients who died before 12 h and were excluded from the LC H0–H12 analysis, non-survivors were significantly older, had higher severity scores, and presented more frequently with hemorrhagic shock. Predictive performance was evaluated using ROC curves and multivariate logistic regression. The composite prognostic score was assessed using bootstrap internal validation (1000 resamples) to provide an optimism-adjusted AUC estimate. Results: Among 318 patients (median age 36 years; 86.5% male), hyperlactatemia (>2.2 mmol/L) was present in 70.1% at admission and persisted in 39.9% at 12 h. Non-survivors exhibited higher lactate levels and lower LC at all time points. LC H0–H12 demonstrated the best predictive performance for in-hospital mortality (AUC = 0.75; 95% CI [0.69–0.81]; p < 0.001). For early mortality (≤48 h), LC H0–H12 achieved an AUC of 0.80 (95% CI [0.71–0.89]; p < 0.001). A composite prognostic score incorporating age >60 years, GCS ≤ 7, prothrombin time ≤ 55%, pH ≤ 7.29, and LC H0–H12 > −2.93 %/h demonstrated good discrimination (AUC = 0.84; optimism-adjusted AUC = 0.82). Conclusions: Lactate levels and 12 h lactate clearance are valuable prognostic markers in severe trauma. Given the inherent survivorship bias affecting the LC H0–H12 analysis, its prognostic performance should be interpreted with appropriate caution and within a multimodal clinical assessment. The proposed composite score is promising but requires prospective external validation before clinical implementation. Full article

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

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18 pages, 13455 KB

Open AccessReview

Common and Uncommon Splenic Lesions: A Review

by Rajvir Teja, Evan Allarie and Christopher Fung

Diagnostics 2026, 16(15), 2462; https://doi.org/10.3390/diagnostics16152462 - 4 Aug 2026

Viewed by 640

Abstract

Background/Objectives: Briefly review the imaging and pathologic findings associated with common and uncommon splenic lesions. These lesions are often incidental and cause a diagnostic dilemma in determining the need for further work-up and follow-up. Methods/Results: A step-by-step review of splenic lesions [...] Read more.

Background/Objectives: Briefly review the imaging and pathologic findings associated with common and uncommon splenic lesions. These lesions are often incidental and cause a diagnostic dilemma in determining the need for further work-up and follow-up. Methods/Results: A step-by-step review of splenic lesions will be provided. This includes general demographics, fundamental pathology, and key imaging features. Conclusions: Splenic lesions are often challenging due to their relatively uncommon presentation, predominantly incidental detection, and broad age of incidence. The vast majority of these lesions, however, are benign. Correlation with the patient demographics and specific elements of the patient history will often significantly narrow the differential diagnosis. Full article

(This article belongs to the Special Issue Detection and Characterization of Focal Lesions in the Solid Abdominal Organs)

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12 pages, 7817 KB

Open AccessCommunication

Is Visual Vertical Perception Altered in Children and Adolescents with Spinal Misalignment? A Cross-Sectional Study

by Alessandro Picelli, Nicola Turri, Rita Di Censo, Irene Chignola, Antonella Dell’Orco, Ilaria Di Maria, Gaspare Crimi, Mirko Filippetti, Nicola Smania and Valentina Varalta

Diagnostics 2026, 16(15), 2461; https://doi.org/10.3390/diagnostics16152461 - 4 Aug 2026

Viewed by 260

Abstract

Background/Objectives. Spinal misalignment in childhood and adolescence may be associated with altered sensory integration and body representation. The subjective visual vertical reflects visual, vestibular, and somatosensory integration, but its relationship with pediatric spinal misalignment remains uncertain. This study investigated the subjective visual [...] Read more.

Background/Objectives. Spinal misalignment in childhood and adolescence may be associated with altered sensory integration and body representation. The subjective visual vertical reflects visual, vestibular, and somatosensory integration, but its relationship with pediatric spinal misalignment remains uncertain. This study investigated the subjective visual vertical using two complementary paradigms. Methods. This exploratory, single-center, cross-sectional study included participants aged 7–17 years with clinically identified spinal misalignment. Participants underwent standardized physiatric assessment and subjective visual vertical testing using a luminous-line test and the Bucket Test. Spearman’s rank correlations examined associations with clinical and radiographic variables, with false-discovery-rate control using the Benjamini–Hochberg procedure. Radiographic analyses were restricted to participants with available imaging. Results. Fifty-seven participants were included (mean age 12.8 years, SD 2.25), and all completed both tests. Mean subjective visual vertical was 0.053° (SD 0.953) with the luminous-line test and −0.561° (SD 1.165) with the Bucket Test. Radiographs were available for 21 participants. No association remained significant after false-discovery-rate correction. Two luminous-line associations were nominally significant before correction: primary lumbar curve presence (ρ = −0.278, p = 0.036) and secondary thoracolumbar curve presence (ρ = −0.324, p = 0.015); both had q = 0.721. The tests were moderately correlated (ρ = 0.493, p < 0.001). Radiographic sensitivity and subgroup analyses showed no significant findings. Conclusions. Subjective visual vertical was not robustly associated with spinal misalignment characteristics in this modest, clinically heterogeneous cohort. Larger controlled studies with standardized imaging and adequately powered severity groups are required. Full article

(This article belongs to the Special Issue Orthopedics and the Musculoskeletal System: Clinical Diagnosis and Management)

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20 pages, 649 KB

Open AccessArticle

Norms for Automatic Estimation of White Matter Hyperintensities Burden: LST-AI Service in neuGRID

by Alberto Boccali, Silvia De Francesco, Claudio Crema, Claudio Demaria, Cesare M. Baronio, Damiano Archetti and Alberto Redolfi

Diagnostics 2026, 16(15), 2460; https://doi.org/10.3390/diagnostics16152460 - 4 Aug 2026

Viewed by 303

Abstract

Background: White Matter Hyperintensities (WMH) are common MRI markers of cerebral small-vessel disease and are associated with cognitive impairment and dementia. Deep Learning (DL) tools have improved WMH segmentation, enabling faster and more reproducible lesion quantification. However, the lack of normative reference [...] Read more.

Background: White Matter Hyperintensities (WMH) are common MRI markers of cerebral small-vessel disease and are associated with cognitive impairment and dementia. Deep Learning (DL) tools have improved WMH segmentation, enabling faster and more reproducible lesion quantification. However, the lack of normative reference frameworks limits the clinical and translational use of WMH volumes. Aims: to develop and validate normative reference curves for automated WMH quantification and to define clinically useful thresholds for rule-out and rule-in interpretation in memory-clinic settings. Methods: We developed age- and sex-adjusted WMH normative models for 2D (n = 788) and 3D (n = 895) FLAIR acquisitions in cognitively normal individuals aged 40–95 years. WMH volumes were segmented using LST-AI and normalized to total intracranial volume. Normative percentiles were derived using Generalized Additive Models for Location, Scale and Shape (GAMLSS) with a Johnson’s SU distribution and externally validated in 458 individuals spanning cognitively normal (CN), mild cognitive impairment (MCI), and dementia groups from two validation cohorts. Normative distributions have been made available through neuGRID, an online platform providing AI-based tools for neuroimaging analysis. Results: WMH burden increased progressively with age in both normative datasets and showed a stepwise increase across the cognitive continuum from CN to MCI and dementia. The optimal balanced thresholds corresponded to the 92nd percentile for the 2D model and the 85th percentile for the 3D model, yielding areas under the receiver operating characteristic curve (ROC-AUCs) of 0.71 (95% CI: 0.63–0.78) and 0.68 (95% CI: 0.61–0.74), respectively. Secondary threshold analyses highlighted complementary operating characteristics, with the 2D model favoring sensitivity and the 3D model favoring specificity, supporting their potential use in sequential diagnostic workflows. Conclusion: This study provides an externally validated normative framework for interpreting LST-AI-derived WMH burden through the neuGRID single-case service. The proposed modality-specific norms enable standardized identification and contextualization of elevated WMH burden and may support clinical stratification, second-opinion assessment, and research applications in cognitive disorders. Full article

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

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4 pages, 3332 KB

Open AccessInteresting Images

Disproportionate Subgaleal Hemorrhage in an Infant: Abuse or Bleeding Disorder?

by Chih-Hao Wang, Po-Chih Lin and Jen-Yin Hou

Diagnostics 2026, 16(15), 2459; https://doi.org/10.3390/diagnostics16152459 - 4 Aug 2026

Viewed by 278

Abstract

Subgaleal hemorrhage is uncommon in infants beyond the newborn period and, when disproportionate to the reported causal trauma, raises suspicion for child abuse. We describe a 9-month-old girl who developed a large right subgaleal and small epidural hematoma after a 50 cm fall. [...] Read more.

Subgaleal hemorrhage is uncommon in infants beyond the newborn period and, when disproportionate to the reported causal trauma, raises suspicion for child abuse. We describe a 9-month-old girl who developed a large right subgaleal and small epidural hematoma after a 50 cm fall. Initial abuse evaluation was negative, and standard coagulation tests were normal, although von Willebrand factor (vWF) activity was elevated. However, repeat testing 2 months later revealed markedly reduced vWF antigen and activity, suggestive of type 1 von Willebrand disease (vWD). This case highlights that disproportionate bleeding after minor head trauma should prompt evaluation for both non-accidental injury and occult bleeding disorders, and that variability in vWF levels necessitates repeat testing for accurate interpretation. Full article

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

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12 pages, 992 KB

Open AccessArticle

Ultrasound-Based Severity Stratification in Carpal Tunnel Syndrome: Median Nerve Cross-Sectional Area for Distinguishing Severe from Moderate Disease

by Işıl Peker, Abir Alaamel and Nilgün Cengiz

Diagnostics 2026, 16(15), 2458; https://doi.org/10.3390/diagnostics16152458 - 4 Aug 2026

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Abstract

Background: High-resolution ultrasound is increasingly used as a complementary tool in carpal tunnel syndrome (CTS), but the value of median nerve cross-sectional area (CSA) for severity stratification remains uncertain. This study evaluated whether median nerve CSA measured at the pisiform level can distinguish [...] Read more.

Background: High-resolution ultrasound is increasingly used as a complementary tool in carpal tunnel syndrome (CTS), but the value of median nerve cross-sectional area (CSA) for severity stratification remains uncertain. This study evaluated whether median nerve CSA measured at the pisiform level can distinguish severe from moderate CTS classified according to the Bland grading scale. Methods: This prospective cross-sectional study included 72 participants: moderate CTS (n = 34), severe CTS (n = 24), and healthy controls (n = 14). Nerve conduction studies, abductor pollicis brevis needle electromyography, and ultrasound examinations were performed on the same day. CSA was measured three times by a blinded examiner, and the mean value was used for analysis. Correlation, age-adjusted linear regression, and receiver operating characteristic curve analyses were performed. Results: Median nerve CSA increased progressively from controls to moderate and severe CTS groups (8.0 ± 1.1, 16.5 ± 4.6, and 19.8 ± 3.4 mm², respectively; p < 0.001), with significant pairwise differences. Intraobserver and interobserver reliability were excellent (ICC = 0.95 and 0.91, respectively). CSA correlated positively with distal motor and sensory latencies and inversely with compound muscle action potential and sensory nerve action potential amplitudes. CSA also showed a weak positive association with neurogenic motor unit action potentials. In age-adjusted regression analysis, distal motor latency remained independently associated with CSA (B = 0.873, p = 0.002). A CSA cut-off of 18.5 mm² distinguished severe from moderate CTS with an area under the curve (AUC) of 0.728, sensitivity of 66.67%, and specificity of 79.41%. Conclusions: Median nerve CSA measured at the pisiform level may provide useful adjunctive structural information for CTS severity assessment and may show moderate discriminatory performance for differentiating severe from moderate CTS. CSA should be interpreted in conjunction with clinical and electrodiagnostic findings rather than as a stand-alone severity marker. Full article

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

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16 pages, 1086 KB

Open AccessArticle

Diagnostic Accuracy of Body Mass Index, Bioelectrical Impedance Analysis, and Waist-to-Hip Ratio Against DEXA for Obesity in Saudi Arabia: A Cross-Sectional Study

by Haifa F. Alotaibi, Saleh A. Alqahtani, Alanoud Alfraidi, Jamala Selan, Feras Altunusi, Abdulrahman Albatly, Shadan AlMuhaidib, Hanan Taib, Amr Arafat and Waleed Alhazzani

Diagnostics 2026, 16(15), 2457; https://doi.org/10.3390/diagnostics16152457 - 4 Aug 2026

Cited by 1 | Viewed by 460

Abstract

Background/Objectives: Body mass index (BMI) is the most widely used measure for obesity classification, yet it does not directly measure body fat and may substantially underestimate obesity prevalence. Simultaneous evaluation of the diagnostic accuracy of bioelectrical impedance analysis (BIA), BMI, and waist-to-hip [...] Read more.

Background/Objectives: Body mass index (BMI) is the most widely used measure for obesity classification, yet it does not directly measure body fat and may substantially underestimate obesity prevalence. Simultaneous evaluation of the diagnostic accuracy of bioelectrical impedance analysis (BIA), BMI, and waist-to-hip ratio (WHR) against dual-energy X-ray absorptiometry (DEXA) for obesity classification is lacking in Saudi Arabia. We aimed to quantify the diagnostic performance of these three surrogate measures against DEXA in Saudi adults. Methods: We conducted a cross-sectional diagnostic accuracy study reported according to the STARD guideline at Prince Sultan Military Medical City, Riyadh, Saudi Arabia. We enrolled a convenience sample of 399 adults aged 18–65 years recruited from primary health care and outpatient clinic waiting areas. Each participant underwent InBody 770 BIA, anthropometric measurements (BMI, WHR), and DEXA (Lunar iDXA, GE) on the same day. We evaluated BIA body fat percentage against DEXA body fat percentage, BMI ≥ 30 kg/m² against DEXA body fat percentage and fat mass index (FMI)-defined obesity, and WHR against the DEXA android-to-gynoid ratio. We calculated sensitivity, specificity, positive and negative predictive values, likelihood ratios, and area under the receiver operating characteristic curve (AUC), overall and stratified by sex. Results: DEXA classified 86.0% of participants as having obesity, compared with 62.9% by BIA and 24.8% by BMI; against DEXA body fat percentage, BMI ≥ 30 kg/m² had a sensitivity of 28.9% and specificity of 100%. When FMI replaced body fat percentage as the reference standard, BMI sensitivity increased to 68.5% (specificity 97.3%, AUC 0.95). BIA achieved a sensitivity of 72.3%, specificity of 94.4%, and AUC of 0.86. WHR had the lowest sensitivity for central obesity (54.0%, specificity 94.8%, AUC 0.80). BIA showed the strongest correlation with DEXA body fat percentage (Spearman ρ = 0.82), followed by BMI (ρ = 0.60). Conclusions: BMI alone missed two-thirds of participants with DEXA-defined obesity in this Saudi adult cohort. Although BIA was more sensitive, it still missed 27.7% of individuals with DEXA-defined obesity. These findings support integrating body composition assessment into clinical practice and suggest that national obesity prevalence estimates based on BMI alone substantially underestimate the true burden. Full article

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

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22 pages, 1621 KB

Open AccessArticle

A Self-Controlled Benchmark of Retrieval-Augmented Generation for Large Language Models on Clinical Guideline Questions

by Andreas Vollmer, Lara Schorn, Felix Schrader, Norbert Kübler, Christoph Sproll, Michael Vollmer, Daman Deep Singh and Babak Saravi

Diagnostics 2026, 16(15), 2456; https://doi.org/10.3390/diagnostics16152456 - 4 Aug 2026

Viewed by 518

Abstract

Background/Objectives: Large language models (LLMs) show promise for clinical decision support, yet their accuracy in interpreting specialized medical guidelines remains uncertain. Retrieval-augmented generation (RAG) may enhance performance by grounding responses in authoritative knowledge bases. This study aimed to compare the accuracy, comprehensiveness, [...] Read more.

Background/Objectives: Large language models (LLMs) show promise for clinical decision support, yet their accuracy in interpreting specialized medical guidelines remains uncertain. Retrieval-augmented generation (RAG) may enhance performance by grounding responses in authoritative knowledge bases. This study aimed to compare the accuracy, comprehensiveness, and safety of RAG-enhanced versus standard LLMs for answering clinical questions derived from the German S3 guideline for oral cavity carcinoma. Methods: We conducted a prospective, single-blind benchmark study evaluating six LLMs: one RAG-enhanced model (Custom GPT with guideline access), one consensus-based model (ConsensusGPT), and four standard models (DeepSeek-V3.2, Mistral Small 3.2, Qwen3-Next-80B, GPT-OSS-120B). Fifty clinical questions covering 17 guideline domains were presented to each model three times, yielding 900 evaluations. Three expert reviewers assessed responses using 5-point Likert scales for accuracy, comprehensiveness, and clarity, under a single-blind procedure, the effectiveness of which was tested by a pre-specified manipulation check. We then ran a paired within-model experiment in which each base model was queried with and without guideline access through a transparent, openly released retrieval pipeline, and scored every response with a condition-blind automated judge alongside deterministic retrieval metrics computed from the logs. Secondary outcomes included hallucination rates and guideline citation behavior. Inter-rater reliability was assessed using intraclass correlation coefficients (ICCs). Results: In a paired within-model design that held each base model fixed, adding transparent guideline retrieval improved accuracy—significantly in the three weaker open-weight models (Mistral, Qwen3, and GPT-OSS) and directionally in the already-strong DeepSeek and GPT-5 bases. Because a pre-specified blinding check found that experts could still identify retrieval-augmented answers with 98.5% accuracy, we anchored causal interpretation on measures that do not depend on the human raters, ranked by their independence: deterministic, log-derived retrieval metrics first, and then an automated, condition-blind LLM judge, whose agreement with the experts (Spearman ρ = 0.81, 95.7% within-one agreement) establishes shared calibration rather than independence from their bias. Deterministically from the retrieval logs, citation groundedness rose from 0% to 51–89% and retrieval recall@5 was 92%. On the judge, content-level hallucination fell from 42% to 4% and accuracy rose by a pooled +0.64 points (95% CI 0.47–0.80); the accuracy gain persisted after adjustment for response length (+0.48, 95% CI 0.22–0.73), which retrieval shortened rather than lengthened. The accuracy gain was large for weaker base models and small or non-significant for already-strong ones, whereas the hallucination and auditability gains were consistent across all models. The human ratings reproduced the judge’s accuracy effect (+0.61, 95% CI 0.49–0.74), and GPT-5 run through the transparent pipeline showed no significant difference from the proprietary Custom GPT (judge accuracy 4.48 vs. 4.58). Conclusions: Guideline retrieval yields a reproducible, largely base-independent improvement in the safety and auditability of LLM answers to clinical guideline questions, with accuracy gains concentrated in weaker base models. Because retrieval-augmented answers are recognizable to experts, rigorous evaluation should rely on rater-independent measures, and residual hallucination continues to require human oversight. Full article

(This article belongs to the Special Issue AI-Driven Precision Medicine: Innovations in Diagnosis, Prognosis, and Management Response)

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Diagnostics, Volume 16, Issue 15 (August-1 2026) – 187 articles

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