Diagnostics doi: 10.3390/diagnostics16213469

Authors: Emre Şancı Feride Fulya Ercan Hamza Çıldır Başak Bayram Adile Öniz Özgören Kürşad Kutluk Neşe Çolak

Background. Intravenous (IV) thrombolysis is the standard of care for acute ischaemic stroke (AIS), yet there is still no objective bedside tool for monitoring the brain continuously during the infusion. Near-infrared spectroscopy (NIRS) provides non-invasive, continuous measurement of regional cerebral oxygen saturation (rSO2). We evaluated whether bilateral frontal NIRS, and in particular the absolute interhemispheric difference in rSO2 (ΔNIRS), tracks the clinical trajectory of patients receiving IV alteplase in the emergency department (ED). Methods. A prospective observational cohort study was conducted in the ED of a tertiary university hospital. Consecutive adults receiving IV alteplase for AIS were screened, and those enrolled underwent continuous bilateral frontal NIRS monitoring. Bilateral rSO2, ΔNIRS, vital signs, Glasgow Coma Scale (GCS) and National Institutes of Health Stroke Scale (NIHSS) were recorded at baseline and at 0, 15, 30, 45, 60 and 120 min after the start of the infusion. Patients were classified by clinical trajectory during monitoring as improvement, no change, or deterioration. Results. Forty-one patients were analyzed (26 female, 63.4%; mean age 73.6 ± 14.8 years); 15 (36.6%) improved, 21 (51.2%) showed no change and 5 (12.2%) deteriorated. In the whole cohort, absolute rSO2 rose only slightly in the affected hemisphere and did not change in the unaffected hemisphere. However, affected-hemisphere rSO2 rose significantly in the improvement group (median 59 to 67; p = 0.001) and fell significantly in the deterioration group (p = 0.015). ΔNIRS narrowed from a median of 4 (IQR 3–9) at baseline to 1 (IQR 0–5) at 120 min in the improvement group (p = 0.034) and did not change significantly in the other groups. The two patients with acute complications desaturated bilaterally. NIHSS correlated strongly and inversely with GCS at every time point (ρ = −0.74 to −0.84; all p < 0.001). Conclusions. During IV thrombolysis in the ED, continuous bilateral frontal NIRS tracked the clinical trajectory. Because recanalisation and reperfusion were not assessed independently, what NIRS paralleled was the clinical course, not reperfusion itself. These hypothesis-generating findings warrant larger studies that validate ΔNIRS against perfusion or vascular imaging.

Diagnostics doi: 10.3390/diagnostics16213468

Authors: Jamal Hasoon Jenna Chuan Grant H. Chen Christopher L. Robinson Omar Viswanath Alan D. Kaye Alaa Abd-Elsayed Thomas T. Simopoulos Jatinder Gill

Background: Sacroiliac (SI) joint pain contributes to chronic axial low back pain, but diagnosis remains challenging because no single historical feature, physical examination maneuver, imaging finding, or injection response is universally accepted as definitive. Although guidelines recommend multimodal assessment, less is known about how interventional pain physicians diagnose SI joint pain in real-world practice. Objective: We aim to describe self-reported diagnostic practices for suspected SI joint-mediated pain among interventional pain physicians. Study Design: Exploratory cross-sectional survey. Methods: An anonymous, voluntary SurveyMonkey questionnaire was distributed between 1 January 2026, and 20 June 2026, to physicians practicing interventional pain medicine through academic institutional email distribution, professional contacts, and social media platforms. The present analysis focused on survey items related to physician specialty, practice setting, diagnostic approach, discordance between history and physical examination, use of diagnostic injections, estimated prevalence of SI joint pain, and management when SI joint and lumbar facet pain coexist. Results: Forty-eight physicians initiated the survey, although some respondents skipped individual items; therefore, item-level response totals ranged from 47 to 48. Respondents were predominantly anesthesiologists (72.3%) and most commonly practiced in academic medical centers (58.3%). All incorporated history and physical examination into their primary diagnostic approach, and 62.5% also included diagnostic injection. A single diagnostic injection was reported by 59.6%, whereas 27.7% routinely used two or more. Conclusion: Respondents reported multimodal clinical assessment with variation in diagnostic injection strategies. This small, self-selected sample describes practice patterns and does not establish national consensus, diagnostic standards, or population prevalence.

Diagnostics doi: 10.3390/diagnostics16213467

Authors: Florina Popa Cosmin Alec Moldovan Corina-Cecilia Manole-Pălivan Cristina Stănescu Răzvan Adam

Background/Objectives: Digital orthopedic technologies are often evaluated as isolated tools even though clinical use depends on a sequence of transformations from diagnosis to intervention. This literature-informed conceptual framework defines the Image-to-Intervention (I2I) pathway and distinguishes diagnostic adequacy, geometric validity, biomechanical validity, decision relevance, execution accuracy, and patient-level outcomes. Methods: The orthopedic and cross-domain literature on imaging, segmentation, 3D modeling, additive manufacturing, computational modeling, patient-specific instrumentation, navigation, and digital twins was purposively mapped to I2I stages. Study design and validation function were recorded separately; the review was a purposive conceptual synthesis rather than a systematic evidence appraisal; no formal risk-of-bias or certainty assessment was performed. Results: The framework uses an early eligibility checkpoint before resource-intensive modeling and a later model-informed decision checkpoint. Nine provisional uncertainty and failure domains identify measurement, transformation, model-form, decision, implementation, and feedback problems without treating them as equivalent errors. A multidimensional maturity profile replaces a universal ordinal ladder. Among 81 retained research sources, 9 were systematic reviews or meta-analyses, 5 were narrative or current-concepts reviews, and 7 were randomized controlled trials; the remainder comprised non-randomized comparative, observational, case-based, technical, cadaveric, synthetic-surrogate, and computational studies. Direct empirical stage mappings were non-exclusive and were most frequent for I2I-4 and I2I-5 (33 sources each); guidance applicability was counted separately. Because the bibliography was purposively assembled, these distributions describe only the cited corpus. Conclusions: I2I complements rather than replaces established guidance for diagnostic efficacy, surgical innovation, computational-model credibility, AI reporting, and medical 3D printing. Its taxonomy, maturity profile, and reporting domains remain provisional and require consensus development and independent reliability testing before clinical or regulatory use.

Diagnostics doi: 10.3390/diagnostics16213466

Authors: Shujing Lyu Eva González-Angulo

Oral squamous cell carcinoma (OSCC) accounts for approximately 90% of oral malignancies, and most cases arise from oral potentially malignant disorders (OPMDs) against a background of chronic inflammation. Periodontitis, a highly prevalent chronic inflammatory disease, is increasingly implicated as a risk factor for OSCC, yet the mechanistic link between these conditions remains unclear. This review proposes that immunosenescence—the age-related decline in immune function—may provide this link. We synthesise evidence indicating that periodontitis promotes immune ageing in oral and systemic immune compartments, encompassing T-cell exhaustion, the accumulation of senescent immune cells, and a pro-inflammatory senescence-associated secretory phenotype (SASP); together, these changes progressively weaken local immunosurveillance. On this basis, we introduce the “immune-senescent switch” as a conceptual framework—explicitly distinguished from established evidence—in which senescence is hypothesised to initially act as a tumour-suppressive barrier in early OPMDs but to be converted into a tumour-promoting force by chronic, periodontitis-driven immunosenescence. We critically evaluate the supporting evidence, including the single-arm phase 2 COIS-01 trial (n = 24), in which senolytics combined with anti-PD-1 therapy achieved a 33.3% major pathological response rate in resectable head and neck squamous cell carcinoma, while emphasising the preliminary, hypothesis-generating nature of these data. Finally, we discuss emerging senotherapeutic strategies, translational gaps, and future research priorities.

Diagnostics doi: 10.3390/diagnostics16213463

Authors: Shi Yan Huanhuan Liu Yiming Kang Chong Wang Pu Zhang Haipeng Zhou Zijie Huang Guangjun Shi Lubiao An Huidan Zhang Hongyu Zhao Hongbin Xu Ruiqing Ma

Background: Pseudomyxoma peritonei (PMP) is a rare peritoneal malignancy with limited genomic data across different biospecimen types. The extent to which ascites and plasma reflect tissue-detected genomic alterations remains incompletely characterized. This study compared genomic profiles across tumor tissue, ascites, and plasma and explored KRAS-defined molecular features in PMP. Methods: Sixty patients with pathologically confirmed PMP were retrospectively included. Next-generation sequencing (NGS) data were available from tumor tissue in 57 patients, ascites in 40, and plasma in 28, with overlapping specimen availability. Cross-specimen genomic concordance was evaluated in 37 patients with matched tissue–ascites samples, including 28 patients with matched tissue, ascites, and plasma. Exploratory analyses were performed to characterize genomic and pathway-level features across KRAS-defined subgroups. Results: In tumor tissue, KRAS (66.7%), GNAS (31.6%), and TP53 (21.1%) were the most frequently altered genes. Among 28 patients with matched tissue, ascites, and plasma, patient-level concordance was 35.7%. At the mutation level, ascites showed higher tissue-referenced positive percentage agreement (PPA) than plasma (93.1% vs. 36.2%). In the expanded cohort of 37 matched tissue–ascites pairs, ascites achieved a tissue-referenced PPA of 94.2% and revealed additional alterations not detected in the corresponding tissue samples. Exploratory KRAS mutation stratification identified G12D (35.0%), G12X (32.5%), and KRAS-wild-type (wt) (17.5%) tumors as the predominant subgroups. KRAS-mutant tumors harbored more detected genomic alterations and potentially clinically actionable alterations than KRAS-wt tumors. Wnt and PI3K pathway alterations were more commonly observed in the G12D and G12X subgroups, respectively, whereas canonical oncogenic pathway alterations were less frequent in KRAS-wt tumors. Conclusions: PMP exhibits substantial genomic heterogeneity across patients and biospecimen types. Ascites cfDNA showed high concordance with tissue and captured additional genomic alterations, suggesting that ascitic fluid may serve as a complementary source for molecular profiling in PMP. KRAS-defined subgroups exhibited distinct genomic characteristics, although their clinical relevance requires further validation in larger, well-characterized cohorts.

Diagnostics doi: 10.3390/diagnostics16213465

Authors: Furkan Akın Caner Çakır

Background/Objectives: Preoperative prediction of retroperitoneal lymph node (LN) metastasis in epithelial ovarian cancer (EOC) may inform surgical planning and counselling. We evaluated the diagnostic performance of contrast-enhanced computed tomography (CT) for pathological LN metastasis and explored whether adding serum CA-125 to CT findings improves prediction. Methods: This single-centre retrospective diagnostic accuracy study included 97 patients with invasive EOC who underwent primary (n = 81) or interval (n = 16) cytoreductive surgery with histopathological LN assessment (2022–2025) and CT within two months before surgery. Pelvic and para-aortic CT findings were compared with histopathology at the patient and regional levels. A logistic model combining these CT findings with log2-transformed CA-125 was compared with the CT-only model using a likelihood-ratio test and was internally validated by bootstrapping. Results: Pathological LN metastasis was present in 31 patients (32.0%). At the patient level, CT had a sensitivity of 58% and a specificity of 67%; a short-axis threshold of >10 mm increased specificity to 94% (sensitivity 23%). Adding CA-125 to the CT model improved model fit (likelihood-ratio p = 0.019) and discrimination (optimism-corrected area under the curve 0.63 vs. 0.70), with acceptable calibration (corrected slope 0.86). The association of CA-125 with LN metastasis was attenuated after adjustment for high-grade serous histology (adjusted odds ratio per doubling 1.18, 95% confidence interval 0.98–1.43) and was not evident in patients with stage III–IV disease. Conclusions: CT has limited sensitivity for LN metastasis in EOC, although enlarged nodes are highly specific. CA-125 may add information to CT findings, but this largely reflects differences in disease extent and histology. These preliminary findings require prospective, externally validated studies before any clinical application.

Diagnostics doi: 10.3390/diagnostics16213464

Authors: Cristian Mircea Neagoș Eugenia Maria Domuța Adriana Neagoș Ileana Anca Sin

Background/Objectives: Real-time intraoperative navigation systems such as SmartNav (Cochlear Ltd., Sydney, Australia) provide objective feedback on electrode array insertion during cochlear implantation, yet it remains unclear whether the parameters they record vary across the device- and patient-level factors a surgeon selects between. This study compared intraoperative insertion dynamics and electrophysiological parameters across electrode array design (CI622 slim-straight versus CI632 slim-modiolar), surgical approach (round window versus cochleostomy), and patient age (children versus adults). Methods: Twenty-nine consecutive implantations in 26 patients (three children implanted bilaterally) performed with SmartNav monitoring were analysed. Insertion angle, insertion speed, total insertion time, the number of contacts (of 22) with in-range impedance, and the number of contacts (of 22) with a measurable neural response telemetry (NRT) response were extracted from device logs and operative records; insertion kinetics were available for 22 of 29 implantations. Distributions were non-normal, so comparisons used the Mann–Whitney U test with rank-biserial effect sizes, Fisher’s exact test, Kruskal–Wallis test, and Spearman correlation. Exploratory multivariable regression, Brown–Forsythe variance testing, bootstrap effect sizes, and outlier-inclusive and one-ear-per-patient sensitivity analyses were additionally applied; no correction for multiple comparisons was made. Results: The CI632 array was advanced faster per electrode than the CI622 (median 0.33 versus 0.56 s/electrode; n = 5 versus 16; p = 0.015; rank-biserial r = −0.75; bootstrap 95% CI −1.00 to −0.38), but the difference was not significant when one implausible outlying value was retained (p = 0.113). Impedance and NRT status were modestly correlated (ρ = 0.388, p = 0.037, uncorrected) and unchanged after adjustment for age band (partial ρ = 0.389), but were not significant in the one-ear-per-patient analysis. The study was unable to detect a difference between age groups or between surgical approaches (five cochleostomies versus 24 round window insertions) in any parameter, and impedance status varied minimally across all strata. Conclusions: Within the limits of a small, unbalanced cohort, SmartNav-derived parameters did not differ detectably across patient age or surgical approach. The data suggest that electrode array design is associated with per-electrode insertion pacing, an observation that depends on a single excluded data point and requires confirmation. The impedance–NRT association is exploratory, is consistent with a chance finding once multiplicity is considered, and should not yet be regarded as an intraoperative integrity signal. No clinical outcome was linked to the intraoperative parameters, so no inference about the clinical superiority of either array or approach can be drawn.

Diagnostics doi: 10.3390/diagnostics16213462

Authors: Waner Li Caiyun Han Jiahao Wu Qi Wang Hong Ren Wei Deng

In heart failure with preserved ejection fraction (HFpEF), functional abnormalities may emerge mainly during exercise. Resting investigations may therefore explain exertional symptoms only partly. Exercise cardiovascular magnetic resonance (Ex-CMR) measures chamber volumes, deformation and blood flow during physiological stress to assess cardiovascular reserve. This review examines the technical foundations of Ex-CMR and its applications in HFpEF diagnosis, physiological phenotyping and treatment monitoring. It considers the physiological interpretation and clinical evidence for atrial, biventricular and vascular reserve indices, with attention to standardised acquisition, multiparametric assessment and clinical translation.

Diagnostics doi: 10.3390/diagnostics16213461

Authors: Simon Weiner Sarah Perleth Silvia Herbold Anna Ryskal Yanru Wang Xinyu Zhang Florian Hessenauer Heike L. Rittner Mirko Pham Magnus Schindehütte

Background/Objectives: Dorsal root ganglion (DRG) enlargement in radiculopathy reflects inflammatory nerve root responses and correlates with symptom severity. While DRG enlargement can be detected by MRI, it is unclear whether photon-counting detector CT (PCD-CT) acquired during routine periradicular therapy (PRT) enables detection and quantification of DRG volumetric changes in lumbosacral radiculopathy. Methods: This retrospective study included 28 selected patients with unilateral L5 or S1 radiculopathy undergoing PCD-CT-guided PRT followed by confirmed therapeutic response. Three independent blinded readers segmented DRGs on low-dose planning acquisitions. Affected and contralateral DRG volumes were compared using paired Wilcoxon signed-rank tests. Results: Affected DRGs exceeded contralateral volumes in 26 of 28 patients (92.9%). Median symptomatic DRG volume was 341.1 mm3 versus 282.3 mm3 contralaterally (p < 0.001). Median DRG enlargement was +24.0%. The result was consistent across L5 and S1 radiculopathy levels. Inter-reader agreements were high (median Dice similarity coefficients 0.78–0.85, median volumetric similarities 0.93–0.95). Conclusions: PCD-CT enables visualization and quantification of DRG volumetric changes on routine therapeutic imaging of selected patients, extracting biological information from procedural acquisitions. This establishes PCD-CT for investigating nerve pathophysiology and extends CT-based neuroradiological research into biological questions previously limited to MRI.

Diagnostics doi: 10.3390/diagnostics16213460

Authors: Ozlem Busra Dogan Hatice Biltekin

Background: Panoramic radiography is widely used in dental practice, but its two-dimensional projection geometry and anatomical superimposition can obscure periapical radiolucent lesions, particularly in the maxillary anterior region and for novice observers. Methods: This retrospective multi-reader, multi-case study aimed to evaluate the effects of unsharp mask and Gaussian blur filters on the diagnostic performance and interobserver agreement of novice observers in detecting periapical radiolucent lesions on panoramic radiographs. Twenty final-year dental students evaluated 56 panoramic radiographs (28 lesion-positive and 28 lesion-free cases; 224 maxillary anterior teeth) under three imaging conditions (original, unsharp mask, and Gaussian blur). Observers scored lesion presence using a five-point confidence scale. Diagnostic performance (AUC, sensitivity, and specificity) was compared using the Dorfman–Berbaum–Metz/Obuchowski–Rockette multi-reader, multi-case method. Interobserver agreement was assessed using quadratic-weighted Cohen’s kappa and the intraclass correlation coefficient (ICC). Results: Imaging condition significantly affected AUC, sensitivity, and specificity (all p ≤ 0.003). Compared with original images, unsharp mask significantly improved sensitivity (78.2% vs. 52.5%), specificity (90.2% vs. 83.2%), and AUC (0.876 vs. 0.737) (all p < 0.05), with the highest interobserver agreement (ICC = 0.951; κ = 0.476). Gaussian blur significantly reduced sensitivity (40.2%) and AUC (0.655) compared with original images (both p < 0.001). Conclusions: Unsharp mask filtering was associated with improved diagnostic performance and interobserver agreement among novice observers, whereas Gaussian blur was associated with reduced lesion detection performance. These findings suggest that unsharp mask filtering may have potential as an adjunct to radiographic interpretation training.

Diagnostics doi: 10.3390/diagnostics16213459

Authors: Erdoğan Şeyran Azer Gökmen Çağlar Köseoğlu Emre Hafızoğlu

Background: Inflammatory and nutritional biomarkers are associated with survival in gastric cancer; however, their incremental prognostic value beyond routinely available clinical factors and the stability of their associations over time remain uncertain. We compared six routinely available biomarkers within a common clinically adjusted framework and evaluated their associations with overall survival (OS), model performance, temporal variation, and internal robustness. Methods: This retrospective single-center cohort study included 255 patients with gastric adenocarcinoma. A prespecified parsimonious Cox model comprising age, sex, Eastern Cooperative Oncology Group performance status, and metastatic disease at diagnosis served as the clinical reference model. The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index (SII), prognostic nutritional index (PNI), and hemoglobin–albumin–lymphocyte–platelet (HALP) score were added separately. Model fit and discrimination, multiple-testing-adjusted associations, time-varying effects, bootstrap internal validation, and influence-diagnostic sensitivity analyses were assessed. Results: During follow-up, 227 patients (89.0%) died. Median OS was 11.66 months (95% confidence interval [CI], 9.63–13.47), and reverse Kaplan–Meier median follow-up was 88.51 months (95% CI, 69.72–110.59). After adjustment for the prespecified clinical factors, higher NLR, PLR, and SII were associated with increased mortality, whereas higher LMR, PNI, and HALP were associated with lower mortality; all associations remained significant after Benjamini–Hochberg correction (q ≤ 0.007). The clinical model had a C-index of 0.678. Biomarker addition yielded C-indices ranging from 0.682 to 0.695, with the largest numerical increase observed for PNI (ΔC-index, +0.017). The HALP-extended model yielded the numerically lowest Akaike information criterion. Exploratory time-specific estimates suggested stronger biomarker–mortality associations during early follow-up, although the interaction tests did not remain significant after multiplicity correction. Bootstrap-corrected C-indices were 0.689 for PNI, 0.686 for HALP, and 0.682 for SII, with low optimism and successful convergence of all 1000 resamples. Influence-diagnostic sensitivity analyses preserved the direction and statistical significance of these associations. Conclusions: Inflammatory and nutritional biomarkers provided additional prognostic information beyond the prespecified clinical factors. Although all six biomarkers remained associated with OS when evaluated separately, their incremental contribution to overall discrimination was modest. PNI and HALP yielded the most favorable numerical model-performance estimates; however, the absolute differences were modest, and formal paired bootstrap comparisons identified no significant differences between the biomarker-extended models. External and longitudinal validation is required before routine prognostic implementation.

Diagnostics doi: 10.3390/diagnostics16213458

Authors: Jiaqi Yao Peihong Li Tao Guo Xiaoqing Li

Pseudoachalasia is an uncommon condition that clinically, radiographically, and manometrically mimics primary achalasia and is most frequently caused by a malignancy involving the gastroesophageal junction or gastric cardia. Distinguishing pseudoachalasia from a primary motility disorder remains challenging because conventional investigations may initially appear reassuring. We present a patient with progressive dysphagia and weight loss whose initial EGD was interpreted as showing no definite mucosal abnormality and whose HREM demonstrated a manometric pattern consistent with EGJOO. Progressive symptoms prompted repeat endoscopy and EUS; these revealed distinct abnormalities of the proximal gastric wall; targeted biopsies confirmed poorly differentiated gastric adenocarcinoma. Although the initial endoscopic examination showed no evident abnormality, HREM cannot visualize or histologically characterize tissue; therefore, it cannot exclude a structural or malignant etiology. This case illustrates that progressive symptoms should prompt re-evaluation.

Diagnostics doi: 10.3390/diagnostics16213457

Authors: Ngoc Diem Doan Phan Quang Chi Nguyen Trang Thi Thu Nguyen Xuan Thi Huong Nguyen Nhung Huynh Ho Quang Sy Nguyen Thuy Thi Chau Duong Huu Quach Tuyen Kim Cat Vo

Background/Objectives: Sonographic estimated fetal weight (EFW) guides many obstetric decisions. We examined maternal, fetal and sonographic factors associated with EFW error using the Hadlock II, Hadlock III and Shinozuka formulas. Methods: This is a retrospective cross-sectional study of 1262 singleton pregnancies at 30–41 weeks scanned within 3 days before delivery. Accuracy was assessed by mean percentage error (MPE), mean absolute percentage error (MAPE), successful estimation rate (SER; error ≤ 10%), Bland–Altman analysis with regression-based limits of agreement and Deming regression. Formulas were compared with paired tests. Each factor’s contribution was measured as the decrease in Nagelkerke R2 (ΔR2) in multivariable logistic regression; factor × formula interactions were tested with generalised estimating equations (GEE). Results: MAPE was 5.44%, 5.64% and 5.75% and SER 86.2%, 84.2% and 84.5% for Hadlock II, Hadlock III and Shinozuka, respectively; differences between formulas were small (ΔMAPE ≤ 0.31 percentage points). Against birth weight, all three overestimated small and underestimated large fetuses (Deming slopes 0.79–0.85). Birth weight was the strongest correlate of SER (decrease in Nagelkerke R2, 0.052–0.129) and, in the main analysis, the only factor whose effect differed between formulas (p < 0.001); other factors reduced Nagelkerke R2 by <0.02. Sensitivity was 42–66% for the 89 neonates < 2500 g and 18–38% for the 39 neonates ≥ 4000 g; positive predictive values were 78–82% and 88–100%, respectively, the latter based on 8–16 estimates (lower 95% confidence limits, 47–74%). Conclusions: EFW error was mainly associated with fetal size; this pattern, partly due to regression towards the mean, cannot be used as a bedside correction. Other characteristics showed little additional association with accuracy. The differences between the formulas were small, their clinical relevance is unclear, and none is recommended over the others. An EFW of 2500–2999 g does not exclude low birth weight, and an EFW of 3500–3999 g does not exclude a neonate of ≥4000 g.

Diagnostics doi: 10.3390/diagnostics16213456

Authors: Emre Karahan Simge Eşme İrem Öztürk Burak Bilecenoğlu Seçil Aksoy Kaan Orhan

Background/Objectives: Zygomatic implants are commonly used to rehabilitate atrophic maxillae and maxillary defects, offering quicker prosthesis placement than bone grafting, but their placement requires technical precision due to the complexity of the zygomatic region. Trabecular bone quality is a key determinant of implant stability, yet data on the zygomatic bone’s microarchitecture remain limited. This study aimed to evaluate and compare trabecular bone microarchitectural features of the zygomatic bone with three reference sites (first molar region, mandibular condyle, and angle of mandible) using cone beam computed tomography (CBCT). Methods: This retrospective cross-sectional study screened 847 archived CBCT scans from the Ankara University Faculty of Dentistry, of which 99 systemically healthy patients aged 20–30 years were included. Trabecular bone microstructural parameters, including tissue volume, bone volume, percent bone volume, trabecular thickness, trabecular number, trabecular separation, and fractal dimension, were assessed using CTAn software at the zygomatic bone, first molar region, mandibular condyle, and angle of mandible. Results: The zygomatic bone exhibited significantly higher tissue and bone volumes than the other regions but lower percent bone volume and trabecular number; trabecular thickness and separation were greatest in the zygomatic bone, while fractal dimension values were lowest. When pooled across the four regions, significant right–left differences were also observed, with higher tissue volume and pore space on the right side. Conclusions: These findings provide baseline reference data on the zygomatic bone’s trabecular structure in a young, systemically healthy population. Further clinical studies in patient groups more representative of typical zygomatic implant candidates, including both older individuals with age-related maxillary atrophy and younger patients with trauma- or pathology-related bone loss, are needed to confirm the relevance of these findings to implant predictability and safety.

Diagnostics doi: 10.3390/diagnostics16213455

Authors: Amneh Alshawabka Mahmoud Alfatafta Huthaifa Atallah Fahad Alhazmi Mohannad Alkhateeb Anthony McGarry Wa’el Qa’dan

Background/Objectives: The Chippaux–Smirak Index (CSI) measures relative midfoot plantar contact, whereas the six-item Foot Posture Index (FPI-6), navicular drop test (NDT), and resting calcaneal stance position (RCSP) assess static foot posture, change in navicular height, and calcaneal alignment, respectively. This study examined associations among these measures, agreement between CSI and FPI-6 classifications, and measurement reliability in young adults. Methods: This cross-sectional study included 350 young adults, with both feet assessed (700 feet). Two orthotists independently measured CSI, FPI-6, NDT, and RCSP. Generalised estimating equation models accounted for correlations between feet and were adjusted for age, sex, body mass index, and foot side. Agreement was assessed using exact percentage agreement and linear weighted Cohen’s kappa, and reliability using intraclass correlation coefficients (ICCs). Results: After adjustment, each increase of 10 percentage points in CSI was associated with a 2.141-point-higher FPI-6 total score, a 2.660 mm greater navicular drop, and an RCSP that was 3.240° more valgus (all p < 0.001). CSI and grouped FPI-6 classifications agreed for 82.9% of feet (linear weighted κ = 0.664, 95% CI 0.595–0.727). Single-measure interrater ICCs ranged from 0.644 for NDT to 0.884 for CSI. Digital remeasurement of CSI demonstrated excellent intrarater reliability (ICC(A,1) = 0.989). Conclusions: Higher CSI values were associated with a more pronated static foot posture, greater navicular drop, and a more valgus RCSP. Incomplete agreement between CSI and FPI-6 classifications indicates that these methods provide related but distinct information and should be interpreted according to the specific foot characteristic assessed.

Diagnostics doi: 10.3390/diagnostics16213454

Authors: Mariam Shadan Nazoora Khan Mohammad Amanullah Khan

Background/Objectives: Tumour-infiltrating lymphocytes (TILs) have emerged as important indicators of tumour–host immune interaction in breast cancer, with increasing prognostic and predictive significance across molecular subtypes. However, most available evidence is derived from Western populations and focuses predominantly on quantitative stromal TIL assessment, while data regarding morphologic stromal immune architecture in Asian populations remain limited. This study evaluated stromal lymphocytic infiltration patterns and their association with molecular and clinicopathologic characteristics in an Indian cohort of invasive ductal carcinoma of the breast. Methods: This retrospective observational pathology-based study included 231 female patients diagnosed with invasive ductal carcinoma at Jawaharlal Nehru Medical College, Aligarh Muslim University, India, between 2009 and 2014. Stromal lymphocytic infiltration was assessed on haematoxylin and eosin-stained sections using a semi-quantitative four-tier scoring system adapted from Guo et al. with whole-section assessment at ×100 magnification by two pathologists. Associations with tumour grade, tumour size, lymph node status, and molecular subtype were assessed using exact and ordinal tests with Holm correction for multiple comparisons. Results: Luminal breast carcinoma was the most common molecular subtype (59.3%), followed by HER2-positive tumours (22.5%) and triple-negative breast cancer (18.2%). Sparse stromal lymphocytic infiltration (score 1) represented the most frequent pattern overall (46.8%). Significant associations were identified between stromal lymphocytic infiltration and molecular subtype, tumour grade, and lymph node status (Holm-adjusted p < 0.001, p = 0.044 and p = 0.044, respectively). Triple-negative and HER2-positive tumours demonstrated higher proportions of moderate-to-dense (score 2–3) infiltration than luminal tumours (40.5% and 48.1% vs. 16.8%). Score 2–3 infiltration was more frequent in Grade III tumours (51.2%) and, conversely, in lymph node-negative than in lymph node-positive tumours (40.8% vs. 21.9%). No statistically significant association was observed between stromal lymphocytic infiltration and tumour size (Holm-adjusted p = 0.071). Conclusions: Stromal lymphocytic infiltration patterns demonstrate substantial heterogeneity across breast cancer molecular subtypes and are associated with molecular subtype and histologic grade, whereas higher infiltration was more frequent in lymph node-negative tumours. These descriptive associations suggest that stromal immune patterns vary with tumour phenotype rather than tumour size. Semi-quantitative morphologic stromal lymphocyte assessment on routine histopathology is inexpensive and feasible in resource-limited settings; its reproducibility and prognostic value require validation.

Diagnostics doi: 10.3390/diagnostics16213453

Authors: Isabella Nardone Sium Wolde Sellasie Simona Zaccaria Marina Passeri Stefania Falcone Chiara Pecchioli Laura Giurato Luigi Uccioli

Background: Radiofrequency Echographic Multi-Spectrometry (REMS) is an ultrasound-based technique for the assessment of bone mineral density (BMD) that has been proposed as an alternative to dual-energy X ray absorptiometry (DXA) for the diagnosis of osteoporosis. Although previous studies have reported high diagnostic concordance between REMS and DXA, evidence from real-world settings remains limited. The aim of this study was to evaluate the diagnostic performance and agreement between REMS and DXA in a clinical population undergoing BMD assessment. Methods: In this retrospective observational study, 145 subjects undergoing BMD evaluation were assessed with both REMS and DXA. Complete paired examinations were available for 142 patients at the lumbar spine and 134 at the femoral neck. DXA was used as the reference standard. Diagnostic performance of REMS was evaluated by calculating sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Agreement between REMS and DXA diagnostic classifications was assessed using linearly weighted Cohen’s kappa. Mean REMS and DXA measurements were compared using paired Student’s t-tests, whereas agreement between continuous BMD measurements was assessed using Bland–Altman analysis. Receiver operating characteristic (ROC) analysis was performed to evaluate the discriminative performance of REMS T-scores. Results: At the lumbar spine, REMS showed a sensitivity of 50.0% (95% CI: 37.5–62.5), specificity of 65.5% (95% CI: 54.8–74.8), PPV of 50.0% (95% CI: 37.5–62.5), and NPV of 65.5% (95% CI: 54.8–74.8). At the femoral neck, sensitivity was 40.0% (95% CI: 28.1–53.2), specificity 70.9% (95% CI: 60.1–79.7), PPV 48.9% (95% CI: 35.0–63.0), and NPV 62.9% (95% CI: 52.5–72.2). ROC analysis showed limited discriminatory performance for DXA-defined osteoporosis, with AUC values of 0.610 at the lumbar spine and 0.623 at the femoral neck. Linearly weighted Cohen’s kappa values were 0.225 and 0.183, respectively, indicating limited agreement in diagnostic classification. No statistically significant differences in mean BMD or T-score values were detected between the two techniques. Conclusions: In this real-world retrospective cohort, REMS and DXA showed no statistically significant differences in mean BMD or T-score values, but agreement in individual diagnostic classification was limited. These results suggest that REMS may have a complementary role alongside DXA rather than serving as a standalone screening method for DXA-defined osteoporosis in this cohort. Further prospective studies are needed to clarify the clinical significance of REMS–DXA discordant cases and their relationship with fracture risk.

Diagnostics doi: 10.3390/diagnostics16213452

Authors: Weiqing Tang Jingbo Wang Jiliang Ren Xing Liang Ying Yuan Xiaofeng Tao

Background: In this study, we aimed to evaluate the feasibility of a whole-tumor histogram analysis of apparent diffusion coefficient (ADC) values derived from diffusion-weighted imaging (DWI) for predicting adenoid cystic carcinoma (ACC) histological grade and solid-component status. Methods: This retrospective study included 168 patients with primary head and neck ACC who underwent preoperative 3.0 T MRI with DWI, randomly allocated with stratification by grade to a derivation cohort (n = 107) and an internal validation cohort (n = 61). Whole-tumor ADC histogram features were extracted and reduced through correlation analysis, and the two most discriminative features were combined in a logistic regression model. Overall survival was explored using Cox regression. Results: ADC10 alone (the 10th percentile of ADC) had areas under the receiver operating characteristic curve (AUCs) of 0.821 (95% confidence interval [CI] 0.727–0.899) and 0.780 (95% CI 0.643–0.895) for grade III in the derivation and validation cohorts, and 0.743 and 0.709 for solid-component status; adding the low-ADC volume did not improve discrimination (DeLong p ≥ 0.468). The model output was associated with overall survival in the pooled cohort (hazard ratio per standard deviation, 1.627) but not in the validation cohort or after adjustment for grade. Conclusions: ADC10 showed promising discrimination of grade III ACC in internal validation, with no gain from adding the low-ADC volume; the prognostic value is unconfirmed, and multicenter external validation is warranted.

Diagnostics doi: 10.3390/diagnostics16213451

Authors: Mamun Hasan Md Mahfuzur Rahman Jennifer F. May John M. Herre Leryn J. Reynolds Zhili Hao

Aim at: This study evaluates whether cardiovascular (CV) parameters derived from noninvasive arterial pulse signals can reveal subject-specific characteristics in patients with atypical CV dynamics. Methods: Seven special-case patients—including a heart transplant (HTx) recipient and individuals with bradycardia (low heart rate, HR), low dicrotic notch (DN), and intermittent arterial pulse waveform (APW) variations—were analyzed across three visits over the cardiac rehabilitation (CR) period. Radial artery (RA) and carotid artery (CA) signals, acquired using micro-fabricated tactile sensors, were processed using a single-degree-of-freedom time–frequency (SDOF–TF) framework to extract multiple CV parameters. The analysis focused on descriptive characterization of subject-specific CV patterns in individual patients. Results: The patients exhibited highly heterogeneous CV profiles. Individuals with low HR exhibited relatively limited post-exercise HR changes. Individuals with low DN morphology exhibited elevated lower-order harmonic amplitudes. Individuals with intermittent APW variations exhibited cyclic changes in APW morphology at rest and during post-exercise recovery. Although CV patterns at rest differed across individuals, post-exercise assessment revealed more distinctive individual-specific differences, including differences between individuals within the same phenotype-based case subset. Across all patients and visits, RA measurements provided more stable and interpretable subject-specific CV patterns, whereas CA measurements were more susceptible to motion artifacts (MA) and sensor noise. For individuals with intermittent APW variations, the CA signals exhibited extremely poor signal quality, limiting their suitability for physiological interpretation. Conclusions: The SDOF–TF framework enabled the characterization of subject-specific, multi-parameter CV dynamics in these seven special cases. The findings illustrate the potential value of arterial pulse analysis for the individualized characterization of atypical CV dynamics. Future studies involving larger patient cohorts are needed to further investigate these findings and establish their clinical utility.

Diagnostics doi: 10.3390/diagnostics16213450

Authors: Ying-Hsi Chen Dah-Ching Ding

Background/Objectives: Occult endometrial carcinoma, incidentally diagnosed after hysterectomy for presumed benign disease, raises concerns regarding its incidence, the prognostic effects of minimally invasive surgery and morcellation, and subsequent management. This systematic review synthesized the available evidence and performed meta-analysis where appropriate. Methods: PubMed, Scopus, and the Cochrane Central Register were searched using a sensitivity-tested strategy. After de-duplication and screening, 76 studies met the eligibility criteria. Incidence was pooled using a random-effects meta-analysis of proportions with the Freeman–Tukey double-arcsine transformation. Subgroup analyses examined surgical contexts, including hysterectomy for benign disease, morcellation-specific cohorts, and pelvic organ prolapse surgery. Survival and management outcomes were synthesized narratively. Results: Among 68 studies with extractable denominators, the pooled incidence (proportion of hysterectomies with carcinoma on final pathology) of occult endometrial carcinoma following hysterectomy for benign disease was 0.33% (95% prediction interval, 0.04–0.87%). Incidence was lowest in selected morcellation cohorts (0.22%) and higher in unselected benign hysterectomy cohorts (0.33%) and prolapse populations (0.43%; test for subgroup differences, p = 0.03), with substantially higher rates among older patients. The pooled incidence of occult uterine malignancies, including sarcoma, was 0.54%. For endometrial carcinoma specifically, the limited observational evidence did not demonstrate a statistically significant association between power morcellation or laparoscopic surgery and poorer survival, although confidence intervals were wide. However, morcellation was associated with increased mortality among patients with uterine sarcoma. Occult endometrial carcinomas were predominantly early-stage and low-grade, with 81.8% classified as International Federation of Gynecology and Obstetrics IA, and approximately 91% achieving 5-year overall survival. In a small series of selected high-risk patients, completion staging resulted in upstaging in 25% and informed adjuvant treatment decisions. Limited observational data did not demonstrate a statistically significant survival benefit of complementary lymphadenectomy, although estimates were imprecise. Conclusions: Occult endometrial carcinoma occurs in approximately 0.2–0.4% of hysterectomies performed for benign disease, with a pooled incidence of 0.33% and higher rates among older patients. The limited observational evidence did not demonstrate a statistically significant association between minimally invasive surgery or morcellation and poorer survival, but estimates were imprecise; wide confidence intervals and potential residual confounding preclude conclusions regarding oncologic safety. Overall prognosis was favorable. These findings support age-informed preoperative counseling and appropriate endometrial evaluation, with individualized consideration of re-staging when occult carcinoma is identified.

Diagnostics doi: 10.3390/diagnostics16213449

Authors: Nasima Mohammad Helal Jon Zaccary Regala Mujeeb Rahman

Background/Objectives: Gastrointestinal (GI) bleeding is a common, potentially life-threatening condition, and capsule endoscopy (CE) is the principal investigation for suspected small-bowel bleeding after non-diagnostic upper endoscopy and colonoscopy. Because manual review of thousands of CE frames is labor-intensive, artificial intelligence (AI) has been proposed to automate bleeding detection. Methods: Following PRISMA 2020, this systematic review synthesizes 15 peer-reviewed journal studies (2020–2025) applying traditional machine learning, convolutional neural networks, transfer learning, attention-based or hybrid architectures, segmentation, or object detection to GI bleeding detection in CE. Methodological quality was appraised with an AI-adapted risk-of-bias framework informed by QUADAS-2 and PROBAST. Results: Frame-level classification accuracy ranged from 90.6% to 99.9% (median 98.5%; 13 studies), with the lowest values from evaluations closest to clinical practice; the segmentation and detection studies reported a mean intersection-over-union of 86.9% and an mAP@0.5 of 79.0%. Only two studies (13%) were at low risk of bias for validation strategy, none reported patient-level separation of training and test data, only four (27%) used clinical patient data, and none compared AI with conventional endoscopy or clinical outcomes. Conclusions: Current evidence demonstrates high performance on curated datasets but not yet generalizability or clinical readiness; patient-level, external, and prospective multicentre validation is required.

Diagnostics doi: 10.3390/diagnostics16213448

Authors: Andreea Ioana Pruteanu Ioana Păvăleanu Ana Maria Haliciu Ana Maria Mihoci Raluca Anca Balan Emil Anton Sorana Caterina Anton Demetra Gabriela Socolov Razvan Vladimir Socolov

Background/Objectives: Adenomyosis is a common yet frequently underdiagnosed cause of gynecological morbidity, and its definitive diagnosis still relies on histopathological examination of hysterectomy specimens. We aimed to determine the histopathological prevalence of adenomyosis in hysterectomy specimens removed for benign indications, characterize preoperative referral diagnoses and concurrent histopathological findings, and compare our results with the contemporary literature. Methods: We retrospectively analyzed 430 consecutive abdominal hysterectomies performed for benign gynecological indications at a tertiary referral center in Iasi, Romania, between January 2019 and October 2024. Adenomyosis was defined histopathologically. An “incidental” finding was defined as the absence of adenomyosis in the preoperative referral diagnosis, without re-review of the original ultrasound reports. We report prevalence and the incidental rate with Wilson-score 95% confidence intervals (CIs); we used the chi-square test with Yates continuity correction for categorical comparisons and calculated odds ratios (ORs), with correction for multiple comparisons. Results: Adenomyosis was identified in 188 of 430 specimens (43.7%; 95% CI 39.1–48.4%), of which 186 (98.9%; 95% CI 96.2–99.7%) were incidental; adenomyosis was recorded in the referral diagnosis in only 2 cases (1.1%). Endometrial hyperplasia was the only co-finding significantly associated with adenomyosis (OR 2.30; 95% CI 1.48–3.55; p = 0.0002), an unadjusted univariate association that remained significant after multiple-comparison adjustment (adjusted p = 0.0014). No referral diagnosis discriminated adenomyosis status; leiomyoma was frequent in both groups (75.5% vs. 69.0%; not significant). Mean age was 50.0 ± 7.6 years, with no between-group difference (p = 0.112). Conclusions: Approximately two in five women undergoing hysterectomy for benign disease have adenomyosis, and it is rarely suspected preoperatively. Because this study did not test whether structured sonographic assessment improves detection, prospective evaluation of the revised 2022 Morphological Uterus Sonographic Assessment (MUSA) criteria with imaging–histopathology correlation is warranted.

Diagnostics doi: 10.3390/diagnostics16213447

Authors: Prateek Bhatia Sharun Sharun Meenakshi Malhotra Sangeetha Kirubanandhan Parminder Kaur Deepshikha Bhardwaj Rozy Thakur Minu Singh

Introduction: Amplicon-based next-generation sequencing (NGS) is widely used in clinical practice, yet few studies address the impact of fluorometric quality control and of low-volume or compromised paediatric samples on library quantification and sequencing metrics. We reframe this question around a practical goal: whether sub-optimal paediatric DNA can be reliably salvaged for custom-panel amplicon NGS. Materials and Methods: Data from 314 paediatric samples sequenced on 16 custom-designed amplicon panels (Ion Torrent S5) were analysed retrospectively by Qubit input quantity (Group A ≥ 10 ng/µL; Group B < 10 ng/µL) and Nanoquant A260/280 quality (Group C 1.7–1.9; Group D < 1.7 or >1.9), and compared against post-library quantification, mean depth, and ten coverage QC parameters. Method agreement (Bland–Altman, proportional-bias regression), effect sizes (Cliff’s δ), panel-adjusted mixed-effects models and ROC/logistic prediction of library failure were added. Results: Median input was 59.75 ng/µL by Nanoquant and 28.25 ng/µL by Qubit (p < 0.0001); median A260/280 was 1.86. Nanoquant overestimated DNA ~2.1-fold, but Bland–Altman analysis revealed wide, concentration-dependent limits of agreement (mean ratio 2.17×; 95% LoA 0.57–8.33×; proportional-bias p < 0.0001), indicating that no single correction factor is reliable. Group A comprised 91.7% (288/314) and Group B 8.3% (26/314); Group C 75.2% (236/314) and Group D 24.8% (78/314). Median post-library Qubit and mean depth were 1254 vs. 552 ng/mL (p < 0.0001) and 848× vs. 1352× (p = 0.025) for A vs. B, and 1254 vs. 1026 ng/mL (p = 0.049) and 745× vs. 1297× (p < 0.0001) for C vs. D. The higher depth in quantity Group B lost significance after adjusting for panel (mixed-model p = 0.083), identifying it as confounding. Input DNA predicted library failure (<300 ng/mL), with an ROC AUC of 0.79 and an exploratory empirical optimal threshold of ≈21 ng/µL (derived and tested in the same cohort; 14 failure events). None of the ten coverage QC parameters differed across groups. Discussion and Conclusions: Qubit quality control is strongly recommended because Nanoquant inflates readings ~2.1-fold, with no dependable correction factor. Low-volume or compromised paediatric DNA (<10 ng/µL and/or A260/280 outside 1.7–1.9) can be salvaged for amplicon NGS with defined protocol adaptations, with only ~19–23% of the worst-case samples failing library QC and comparable coverage in a small, concentration-matched representative subset (n = 5 per group) that was underpowered for formal equivalence testing. An empirical input threshold of ≈20 ng/µL, roughly double the manufacturer’s minimum, best protects against library failure.

Diagnostics doi: 10.3390/diagnostics16213445

Authors: Cara Spence Visna Rampersad Nicole Williamson Srinivasa Tejaswini Banna Noreen Reed Lindsay Iron Jessica Minon Beverly Wudel Claire Allen Kristin McBain Rick Galli Sean B. Rourke Stuart Skinner

Background: Saskatchewan faces a growing public health challenge, with outbreaks of infectious syphilis and a continued increase in new HIV diagnoses. Rural, remote, and underserved populations experience disproportionate burdens due to barriers to timely testing, diagnosis, treatment, and linkage to care. The Syphilis/HIV Early Rapid Response (SHIVER) project implemented an innovative point-of-care testing (POCT) and treatment model to improve access to rapid diagnosis, immediate treatment, and care for individuals in inner-city, rural, remote, and underserved communities across Saskatchewan, Canada. Methods: Individuals aged ≥16 years were offered POCT for syphilis and/or HIV based on non-random criteria. Standard serology was collected according to provincial guidelines. Participants with a positive syphilis POCT result were offered immediate treatment, when appropriate, and follow-up testing. Those with a positive HIV POCT received counselling, confirmatory testing, and expedited linkage to care. Results: Between February 2023 and November 2024, 1797 participants were enrolled. Syphilis POCT was completed by 1781 participants, including 319 (17.9%) first-time testers. HIV POCT was completed by 1387 participants, including 141 (10.2%) first-time testers. The program achieved a diagnostic yield of 16.45% for syphilis and 3.39% for HIV. Integrating dual POCT in a single encounter increased testing opportunity, improved case detection, and minimized procedural burden for participants. Conclusions: This flexible POCT model successfully expanded access to testing, immediate treatment, and timely linkage to care for populations at the highest risk of syphilis and HIV. Its emphasis on community partnerships and culturally safe service delivery supports a scalable model that can improve access to infectious disease care in underserved communities. Trial Registration: ClinicalTrials.gov (NCT05863117) Date of Registration: 19 April 2023.

Diagnostics doi: 10.3390/diagnostics16213444

Authors: Marta Wacewicz-Muczyńska Wiktoria Krzyżewska Bogumiła Redlarska

Background: Striae distensae (stretch marks) are atrophic skin lesions. Microneedling stimulates collagen remodeling, and high-frequency ultrasonography (HFUS) allows for the evaluation of these tissue changes. Objective: To assess the effectiveness of microneedling in reducing abdominal striae distensae using photographic and HFUS imaging. Methods: Ten women underwent three microneedling treatments at 6–8 week intervals. Skin structure was evaluated before and after the therapy using HFUS and photography. Results: Ultrasound imaging revealed pronounced structural tissue remodeling and a visible reduction in lesion visibility across the cohort. However, quantitative ultrasound shifts did not reach statistical significance in this pilot sample (n = 10), indicating that these findings represent observational trend data. In seven patients, a more homogeneous and ordered collagen structure was observed (increased medium echogenicity), while three showed the opposite trend. Visually, all subjects experienced shallower stretch marks, improved skin texture, evened color, and observational improvement. Conclusions: High-frequency ultrasonography suggests that microneedling is a safe and promising method for tissue remodeling and the clinical reduction of striae distensae.

Diagnostics doi: 10.3390/diagnostics16213446

Authors: Giada Baroni Elena Lucchesini Dan Fruja Ioana Teodora Floarea Ana-Liana Bouroș-Tataru Laura Ioana Rădoi Nicoleta Anamaria Pascalau Corina Dalia Toderescu Georgeta Lucia Piscoi Alexandru Pop

Background/Objectives: Mechanical alignment (MA) has traditionally been the reference alignment strategy in total knee arthroplasty (TKA), whereas kinematic alignment (KA) has emerged as an individualized alternative intended to approximate patient-specific knee anatomy. However, the relationship between postoperative mechanical-axis alignment and functional recovery remains incompletely understood. This study aimed to compare short-term functional outcomes and postoperative mechanical-axis alignment between MA and KA following primary TKA and to investigate the relationship between measured postoperative alignment parameters and functional outcomes. Methods: This single-center retrospective comparative cohort study included 120 patients who underwent primary unilateral TKA for end-stage knee osteoarthritis (KOA) between January 2022 and December 2024; 51 underwent MA and 69 underwent KA. Radiographic assessment included the hip–knee–ankle (HKA) angle, mechanical-axis deviation (MAD), residual varus deformity, and radiographic knee extension deficit. Functional outcomes were assessed using the Knee injury and Osteoarthritis Outcome Score (KOOS), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and the Knee Society Score (KSS). Preoperative, postoperative, and change-from-baseline (Δ) functional scores were evaluated. Analysis of covariance (ANCOVA) was used to assess associations between alignment strategy and postoperative functional outcomes after adjustment for baseline functional scores and relevant covariates. Associations between postoperative radiographic parameters and functional outcomes were additionally assessed. Results: Both alignment groups demonstrated substantial preoperative-to-postoperative functional improvement. MA achieved postoperative HKA alignment closer to the neutral mechanical axis than KA (179.63 ± 1.23° vs. 178.24 ± 2.32°; p < 0.001; FDR-adjusted p < 0.001). Absolute HKA deviation from neutral was lower with MA (0.97 ± 0.83° vs. 2.42 ± 1.62°; FDR-adjusted p < 0.001), as was postoperative absolute MAD (5.19 ± 4.53 mm vs. 7.86 ± 6.76 mm; p = 0.011; FDR-adjusted p = 0.018). KA was associated with a higher unadjusted postoperative KOOS score than MA (84.04 ± 12.33 vs. 77.12 ± 15.65; p = 0.010), whereas postoperative WOMAC (p = 0.206) and KSS (p = 0.843) did not differ significantly between groups. Between-group differences in change from baseline were not statistically significant for KOOS (p = 0.227), WOMAC (p = 0.130), or KSS (p = 0.427). After multivariable adjustment, no statistically significant between-group associations were observed for postoperative KOOS (adjusted β = 2.42; 95% CI, −0.93 to 5.77; p = 0.155), WOMAC (adjusted β = −2.80; 95% CI, −6.73 to 1.14; p = 0.162), or KSS (adjusted β = 1.09; 95% CI, −2.05 to 4.24; p = 0.492). Associations between the postoperative radiographic parameters and functional outcomes were negligible to weak, with none remaining statistically significant after FDR correction. Conclusions: Both MA and KA were associated with substantial short-term functional improvement, with no significant between-group differences in the magnitude of improvement from baseline. MA achieved postoperative alignment closer to the neutral mechanical axis, while the higher unadjusted postoperative KOOS score observed with KA was not statistically significant after adjustment for baseline characteristics and potential confounders. No significant postoperative differences in WOMAC or KSS were observed. The generally weak associations between measured postoperative mechanical-axis parameters and functional outcomes suggest that mechanical-axis alignment alone may not adequately explain short-term functional recovery. Because patient-specific coronal alignment parameters and achievement of the individualized KA target were not quantitatively assessed, the present findings cannot determine whether restoration of patient-specific anatomy was associated with functional outcomes.

Diagnostics doi: 10.3390/diagnostics16213443

Authors: Cristiana Călin Iulia Florentina Burcea Ramona Dobre Cristina Căpățînă Șerban Radian Ionela Baciu Elena Emanuela Braha Cătălina Poiană

Background: Familial isolated pituitary adenomas (FIPA) are characterized by considerable clinical and genetic heterogeneity. Although germline pathogenic variants in AIP account for a subset of cases, most FIPA families remain genetically unexplained. We aimed to describe the clinical characteristics, tumor phenotype, treatment outcomes, and targeted genetic evaluation of FIPA families from a tertiary endocrine referral center. Methods: We retrospectively identified FIPA families among patients with pituitary neuroendocrine tumors (PitNETs) evaluated at a tertiary endocrine referral center between 2019 and 2024. FIPA was defined as PitNETs occurring in at least two related individuals without clinical features suggestive of syndromic endocrine disease. Clinical, radiological, histopathological, and genetic data were analyzed. Results: Among 1068 patients with PitNETs, seven FIPA families were retrospectively identified (0.66% of the source cohort), comprising 20 affected individuals. Index cases included four women and three men, with a mean age at diagnosis of 37.1 ± 17.3 years. Somatotroph PitNETs predominated among index cases (5/7), whereas nonfunctioning PitNETs were more frequent among affected relatives (9/13). Six of seven index tumors were macroadenomas, and cavernous sinus invasion was present in two. No pathogenic or likely pathogenic variants in AIP or MEN1 were identified by Sanger sequencing, and multiplex ligation-dependent probe amplification (MLPA) detected no copy number alterations involving AIP, MEN1, or CDKN1B. Conclusions: This series highlights the clinical heterogeneity of FIPA and the differing tumor spectrum between index cases and affected relatives. The absence of pathogenic variants identified by targeted genetic testing further illustrates the genetic heterogeneity of familial pituitary tumor predisposition.

Diagnostics doi: 10.3390/diagnostics16213442

Authors: Maria Cezara Mureșan Marius Bogdan Mureșan Dan Dumitrascu-Biris Zoran Laurențiu Popa Cosmin Citu

Background/Objectives: Cerebroplacental ratio (CPR) is mainly a contemporaneous hemodynamic and prognostic marker but has also been proposed as a marker of impaired growth velocity. We quantified how much third-trimester CPR constrains an individual fetus’s preceding measured growth. Methods: In a retrospective single-center cohort, conditional estimated fetal weight growth (cEFW) was derived in 920 singleton pregnancies and analyzed in 760 fetuses appropriate for gestational age (AGA) at the third-trimester scan (median 32.9 weeks), with umbilical and middle cerebral artery Doppler measurements obtained during the same examination. Quantile regression estimated the conditional/unconditional 10th–90th percentile width of cEFW (width ratio) by within-cohort CPR z-score. Results: Each 1 SD increase in CPR corresponded to 0.100 SD higher cEFW (95% CI 0.040–0.160); the AUC for cEFW ≤ −1 SD was 0.553 (0.479–0.619). Point-estimate width ratios ranged from 0.968 to 1.194 between CPR z −2 and +1, with wide intervals at low CPR. The modeled probability of cEFW ≤ −1 SD was 14.4% (8.5–22.1) at z −2 and 10.5% (8.4–12.9) at z 0. Without AGA restriction (n = 878), the association was stronger (AUC 0.615), but point-estimate width ratios likewise showed no narrowing at low CPR. Conclusions: In AGA fetuses scanned mainly at 31–34 weeks, CPR provided limited individual-level information about preceding measured growth in terms of central 80% width, discrimination and lower-tail probabilities; at very low CPR, meaningful narrowing cannot be excluded. Prognostic value for perinatal outcome was not assessed.

Diagnostics doi: 10.3390/diagnostics16213441

Authors: Gökhan Karataş Ezgi Kula Burcu Orug Köseer

Background/Objectives: We assessed whether preprocedural serum albumin adds prognostic information to the PCI-derived Mehran score for early contrast-associated acute kidney injury (CA-AKI) after elective carotid artery stenting (CAS). Methods: This single-centre retrospective cohort included 121 consecutive elective patients (January 2020–April 2026). The primary model combined the reconstructed Mehran score with albumin < 3.5 g/dL, a conventional threshold fixed in advance. Because the score uses actual contrast volume, the combined model applies only after CAS. The outcome used KDIGO serum creatinine thresholds (≥0.3 mg/dL or ≥1.5 times baseline) from routine second-day testing. Internal validation used 1000 bootstrap resamples. Results: Early CA-AKI occurred in 32 patients (26.4%). Adjusted odds ratios were 1.35 per Mehran point (95% CI 1.13–1.60) and 11.68 for albumin < 3.5 g/dL (95% CI 4.14–32.97). AUC increased from 0.768 to 0.865 (95% CI 0.794–0.937; likelihood ratio χ2 = 24.58, p < 0.001). Corrected AUC, calibration slope, and Brier score were 0.860, 0.96, and 0.132. In exploratory decision curves (20% threshold), corrected net benefit was 0.168 for the combined model and 0.133 for Mehran alone. Conclusions: Low preprocedural albumin added prognostic information to the PCI-derived score and may help select patients for closer renal surveillance after CAS. External validation and prospective impact studies are needed before clinical use.

Diagnostics doi: 10.3390/diagnostics16213440

Authors: Ethel Flores Diana Meza Rene Gonzales Carlos Agudelo-Santos Lilian Sosa Lupe Carolina Espinoza Isaac Zablah

Background/Objectives: Gastrointestinal symptoms are a common reason for primary-care consultation, yet specialist assessment is often inaccessible in rural Central America. We evaluated whether explainable models using inexpensive demographic and lifestyle data can identify community residents aged 12 to 49 years with concurrently elevated gastrointestinal symptom burden. Methods: This was a cross-sectional survey of 1838 residents from 85 communities in five Honduran departments. Elevated symptom burden was defined as at least two of four indicators: recent abdominal pain, heartburn, gastroesophageal reflux, and post-prandial bloating. Model A used eight demographic and lifestyle predictors; Model B added self-reported previous digestive diagnosis. Logistic regression was compared with six machine-learning classifiers under repeated nested five-fold and ten-fold cross-validation and community-grouped cross-validation. Discrimination, calibration, paired differences, community-level uncertainty, decision curves, SHAP explainability and subgroup performance were assessed. Results: Elevated symptom burden affected 840/1838 participants (45.7%, 95% CI 43.4 to 48.0). Model A showed modest discrimination (AUROC 0.663, 95% CI 0.639 to 0.688), while Model B improved performance (AUROC 0.726, 95% CI 0.702 to 0.748) with good calibration (slope 0.955). No flexible learner outperformed logistic regression; the paired AUROC difference with gradient boosting was 0.001 (95% CI −0.008 to 0.010). Within strata of previous diagnosis, discrimination was only 0.621 to 0.643. Model B provided net benefit above screen-all and screen-none strategies at thresholds above approximately 0.25, but reaching 80% sensitivity required flagging 66% of participants. Conclusions: Low-cost information can identify concurrently elevated gastrointestinal symptom burden with moderate accuracy. A parsimonious, well-calibrated logistic regression model performed comparably to more complex methods and is a reasonable candidate for community-based identification of current burden, not for forecasting risk. Prospective external validation and age-specific thresholds are required before clinical implementation.

Diagnostics doi: 10.3390/diagnostics16213439

Authors: Ahmet Halil Sevinç Burcu Hancı Sevinç Erdinç Dinçer Osman Murat İpek Alparslan Çetin Cengiz Çanakcı Orkunt Özkaptan Antonios Koudonas

Background/Objectives: To compare the discriminatory performance of commonly used perioperative risk assessment tools, including the American Society of Anesthesiologists (ASA) Physical Status Classification, Estimation of Physiologic Ability and Surgical Stress (E-PASS), Surgical Outcome Risk Tool (SORT), and modified 5-item Frailty Index (mFI-5), for major postoperative complications after radical cystectomy. Methods: This retrospective observational study included 193 patients who underwent open radical cystectomy for bladder cancer between January 2017 and January 2025. Major postoperative complications were defined as Clavien–Dindo grade III or higher. The discriminatory performance of ASA, E-PASS Comprehensive Risk Score (CRS), SORT, and mFI-5 was assessed using receiver operating characteristic analysis. Pairwise comparisons of the areas under the receiver operating characteristic curves (AUCs) were performed using the DeLong test. Logistic regression models were used to evaluate associations with major complications, and exploratory analyses examined secondary postoperative outcomes. Results: Major postoperative complications occurred in 58 (30.1%) patients. The numerical AUC was highest for E-PASS CRS (0.618, 95% CI 0.536–0.701), followed by SORT (AUC 0.610, 95% CI 0.525–0.694), ASA (AUC 0.595, 95% CI 0.509–0.680) and mFI-5 (AUC 0.578, 95% CI 0.489–0.668). However, pairwise DeLong tests showed no statistically significant difference in discrimination between E-PASS CRS and SORT, or any of the other scores tested. In univariable analysis, high E-PASS CRS, high SORT score and mFI-5 ≥ 2 were significantly associated with major complications, while ASA classification was not. When all scores were entered into the multivariable model at the same time, none of the scores remained statistically significant. Conclusions: All of the risk assessment tools evaluated in this study demonstrated poor discriminatory ability for major postoperative complications following radical cystectomy. Although E-PASS CRS had the highest numeric AUC, its discrimination was not statistically better than the other scores analyzed. Existing risk tools may help with perioperative risk stratification but should not be used as stand-alone prediction models for major postoperative morbidity after radical cystectomy.

Diagnostics doi: 10.3390/diagnostics16213438

Authors: Shonik Ganjoo Samia Haffiane Mohammed El-Aichi Harrison Howell Tarek Aissi Tania Moussa Robert Charlotte Camilla Satragno Corinne Balleyguier Mabel Nuernberg Nathalie Lassau Gabriel Garcia Francois Bidault Laurent Dercle Joya Hadchiti Samy Ammari

Background/Objectives: Differentiating tumor recurrence (TR) from radiation necrosis (RN) remains a significant challenge in the post-radiation management of brain metastases due to their overlapping clinical and radiographic features. Existing imaging techniques often lack the sensitivity and specificity necessary for accurate differentiation. This study evaluates the performance of a novel suite of imaging biomarkers characterizing microvasculature, blood flow dynamics, and tumor oxygen utilization in distinguishing TR from RN, compared with established cerebral blood volume (CBV) measures. Methods: This retrospective study included 119 symptomatic patients with metastatic brain lesions, 7–15 months post-radiotherapy. The training cohort (n = 96, 182 lesions) spanned June 2013 to May 2018, while a separate test cohort (n = 23, 23 lesions) was collected from January 2023 to December 2024. Lesions were classified as TR or RN based on expert consensus, pathology, and long-term follow-up. Eleven imaging biomarkers were assessed in the historical cohort and nine shared biomarkers were evaluated across cohorts, including both standard and novel biomarkers. Standard biomarkers included the Apparent Diffusion Coefficient (ADC), corrected and non-corrected Cerebral Blood Volume (cCBV and ncCBV), and the Relative Amplitude of the Peak (rRHP). Novel biomarkers included Arterial Input Function Delay (Delay), Capillary Transit Time Heterogeneity (CTH and CTH Max), Oxygen Extraction Fraction (OEF), Relative Extravasation Correction (rLeakage), Relative Cerebral Metabolic Rate of Oxygen (rCMRO2), and Coefficient of Variance (COV). For each biomarker, a region of interest was selected from the lesion parenchyma, and a lesion-to-control parenchyma ratio was calculated. Biomarkers were evaluated for their ability to differentiate TR from RN, using the area under the receiver operating characteristic curve (AUC) for univariate analyses and random forest modeling to identify optimal biomarker combinations. Bivariate analyses modeled lesion and control parenchyma as independent variables for each biomarker and compared AUCs for models in both cohorts. Results: In the training cohort, novel biomarkers, including Delay (AUC = 0.994), CTH (AUC = 1.000), CTH Max (AUC = 1.000), OEF (AUC = 0.991), rCMRO2 (AUC = 1.000), and Coefficient of Variance (AUC = 0.993), had higher observed AUC values than cCBV (AUC = 0.930) and ncCBV (AUC = 0.786). In the test cohort, the novel biomarkers did not demonstrate a consistent advantage over cCBV or ncCBV. The random forest model identified an optimal combination of five biomarkers (cCBV, ncCBV, Delay, OEF, and COV) with an AUC of 0.964. Among these, Delay had the highest feature importance, while ncCBV contributed the least. Conclusions: Novel imaging biomarkers demonstrated high discrimination in the training cohort, but this performance was not reproduced in the independent test cohort. The random forest analysis identified a combination of conventional and novel biomarkers with a reported AUC of 0.964. These findings support further investigation of their potential complementary diagnostic value but remain exploratory and require validation in larger prospective multicenter cohorts.

Diagnostics doi: 10.3390/diagnostics16213437

Authors: İsmail Çapar Emre Haylaz Çiğdem Şeker Gediz Geduk Fahrettin Kalabalık Suayip Burak Duman

Background/Objectives: The canalis sinuosus (CS) and its accessory canals (ACs) are neurovascular canals of the anterior maxilla at risk during surgery. We examined their prevalence, side distribution, diameter, localization, and course on cone-beam computed tomography (CBCT) and explored associations with age and sex. Methods: Two observers independently read CBCT images of 603 adults from a single center. Canals were recorded only if they measured at least 0.5 mm, and ACs only if their continuity with the CS could be traced. Age, sex, and side were examined with generalized estimating equations and Benjamini–Hochberg correction. Results: The CS was present in 53.2% of patients, bilaterally in 97.5% of them. ACs were seen in 59.5% of CS-positive patients (31.7% overall). Most ended in the lateral incisor region (26.5%) and ran straight vertically (63.4%). In exploratory analyses, age was associated with the presence of both canals (q = 0.040), whereas sex and side showed no significant association; the CS was wider in men (β = 0.227 mm; q < 0.001). Conclusions: At least one AC was present in 31.7% of patients, and 43.4% of ACs ended at lateral incisor or canine sites. When CBCT is available before anterior maxillary surgery, the planned site should be examined for these canals; demographic associations need confirmation.

Diagnostics doi: 10.3390/diagnostics16213436

Authors: Ayşe Keles

Background/Objectives: Paediatric brain tumour cohorts are small, and deep networks trained directly on volumetric MRI often perform poorly on them. The usual response is a larger architecture. The contribution of the anatomical representation itself has not been isolated as an experimental factor, so it is not known how much of the difficulty is architectural and how much is representational. This study addresses that gap, using supratentorial/infratentorial tumour localisation as a task defined entirely by anatomical geometry. Methods: In 108 paediatric patients with multi-sequence MRI and manual annotation of the tumour and eight anatomical structures, the task, the cohort and the subject-grouped five-fold cross-validation assignment were held fixed while the representation of the input was varied: 3D convolutional networks on raw volumes, the same networks given coordinate and craniocaudal-profile priors, a geometric rule with no fitted parameters, and a patient-level graph whose nodes are anatomical structures, read out by logistic regression or by a graph attention network. All anatomy downstream of the landmarks was predicted out of fold. Comparisons were patient-paired, with bootstrap intervals and Holm-corrected McNemar tests. Results: Balanced accuracy rose from 0.522 on raw voxels to 0.652 with explicit spatial priors, 0.681 for the parameter-free geometric rule, 0.775 for a five-feature linear readout of the graph and 0.838 for the graph attention network; the same decision layer given manual masks reached 0.918. Only the graph attention network exceeded the strongest convolutional baseline significantly (+0.187, Holm-adjusted p = 0.009). Automated segmentation was associated with a 0.143 gap, driven by spatial mislocalisation rather than by missed tumours. Conclusions: For this geometrically defined task and cohort size, representing anatomical structure explicitly was more effective than learning the same geometry from voxels.

Diagnostics doi: 10.3390/diagnostics16213435

Authors: Karina-Alexandra Cojocaru Mariana Pavel-Tanasa Oana Roxana Oprea Larisa Ghemiș Delia Reurean-Pintilei Andra Melissa Tarțău Iris Bararu-Bojan Georgeta Liliana Foia

Background/Objectives: Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder characterized not only by impaired carbohydrate metabolism but also by alterations in lipid and protein metabolism. Hyperglycaemia in T2DM can promote the excessive production of reactive oxygen species (ROS), leading to oxidative stress. 8-Hydroxy-2′-deoxyguanosine (8-OHdG) is a biomarker of oxidative DNA damage commonly used to investigate oxidative stress. Methods: In this cross-sectional analytical observational study, patients diagnosed with T2DM and healthy controls were enrolled. Plasma 8-OHdG concentrations were measured using an enzyme-linked immunosorbent assay (ELISA). Associations between 8-OHdG concentrations and age, fasting blood glucose, and lipid profile parameters were evaluated. These associations were further explored in patient subgroups defined according to glycated haemoglobin (HbA1c) levels. Results: Patients with T2DM had higher plasma 8-OHdG concentrations than healthy controls (Cohen’s d = 1.092; 95% CI, 0.646–1.532; p < 0.001). After adjustment for age, the between-group difference was attenuated, with an adjusted mean difference of 28.84 ng/mL (95% CI, 0.278–57.41; p = 0.048). In the overall cohort, statistically significant correlations were identified between 8-OHdG levels and age (ρ = 0.379; 95% CI, 0.164–0.556; p < 0.001), fasting blood glucose (ρ = 0.266; 95% CI, 0.059–0.474; p = 0.011), and triglycerides (ρ = 0.376, 95% CI, 0.178–0.554; p < 0.001). Stratification of patients according to HbA1c levels revealed no statistically significant differences in 8-OHdG concentrations among the subgroups. Furthermore, none of the correlations examined within these subgroups remained statistically significant after adjustment for multiple testing. Conclusions: Plasma 8-OHdG concentrations were higher in patients with T2DM than in healthy controls, although the magnitude of the between-group difference was attenuated after adjustment for age. In the overall study population, 8-OHdG concentrations were associated with age, fasting blood glucose, and triglyceride concentrations. These findings suggest that 8-OHdG levels may be associated with demographic and metabolic factors. Given the cross-sectional design, these associations should not be interpreted as causal. Further prospective studies with larger cohorts are needed to evaluate the potential clinical relevance of plasma 8-OHdG measurement in T2DM.

Diagnostics doi: 10.3390/diagnostics16203434

Authors: Mansour M. Alqahtani Kathy Willowson Chris Constable Roger Fulton Elizabeth Bailey Sally Ayesa Geoff Schembri Peter L. Kench

Background/Objectives: The purpose of this prospective study was to investigate the preferred reconstruction SPECT parameters for generating reprojected planar images in bone studies, and to evaluate, by visual reader assessment, the feasibility of using these reprojected images as a substitute for traditional planar whole-body (WB) bone scan images. This was a single-centre feasibility study; diagnostic accuracy was not assessed. Methods: Patients referred for planar bone scintigraphy (PBS) and WB-SPECT/CT were prospectively enrolled. Reprojected planar bone scintigraphy (R-PBS) data were generated using forward projection of the three-bed SPECT/CT data. Three nuclear medicine (NM) specialists, blinded to the imaging reconstruction, evaluated both sets of images in a randomised order. The preferred reconstruction parameters for R-PBS were determined by visual assessment using a 4-point ordinal visual scoring scale. A side-by-side comparison of PBS vs. R-PBS was conducted, including assessments of image quality, artefact generation, image preference, and any clinical significance that may affect report interpretation. The agreement between the physicians’ evaluations was measured using the Kappa coefficient test. Results: Of the four reconstruction parameter combinations, 6 iterations, 8 subsets, and a 5 mm Gaussian post-filter yielded the highest visual quality scores. PBS images scored higher on image quality, though this difference was not statistically significant (p > 0.05). The inter-rater agreement for image quality scores was moderate for both PBS and R-PBS images. The results indicate that among the 33 reader-level assessments derived from 11 patient pairs and reviewed by the 3 readers, PBS images were preferred 13 times (~40%), R-PBS 10 times (30%), and no preference was indicated for the remaining 10 (30%). Conclusions: In this small feasibility cohort, R-PBS images derived from fast WB-SPECT/CT data were of visual quality comparable to PBS and may have potential as an alternative to PBS. If confirmed in larger studies with formal diagnostic accuracy assessment, R-PBS could remove the need for a separate PBS acquisition and reduce overall patient imaging time.

Diagnostics doi: 10.3390/diagnostics16203433

Authors: Mohammed Z. Alqahtani Amirah A. Alzaki Ghala M. Asiri Mada H. Al Jibril Bayan M. Alhashidi Khalid W. Binhamran Najmah A. Alotaibi Saad A. Alqahtani Taif M. Alqahtani Maymunah M. Alassiri Assem Gebreal Sarah A. Al Khalid Ghada Mahmoud Ismail Eman A. Alqahtani Ramy Mohamed Ghazy

Background/Objectives: Type 2 diabetes mellitus (T2DM) is a major public health challenge in Saudi Arabia and is associated with substantial morbidity through vascular complications. This systematic review and meta-analysis estimated the pooled prevalence of diabetes-related complications and examined study-level risk factors among Saudi adults with T2DM. Methods: The review followed PRISMA guidance and was registered in PROSPERO (registration number: CRD420251032235). Random-effects models were used, and heterogeneity, risk of bias, small-study effects, subgroup effects, influence, and study-level moderators were assessed. Results: Of 743 records identified, 36 unique, non-overlapping datasets contributed to at least one quantitative synthesis. Study quality was good in 25 studies (69.4%). Pooled prevalences were 24% for retinopathy (95% CI 18–30%; 26 studies), 16% for nephropathy (11–23%; 22 studies), 24% for neuropathy (16–34%; 27 studies), 3% for cerebrovascular stroke (2–6%; 10 studies), 10% for myocardial infarction (MI) and broader coronary heart disease/coronary artery disease (CHD/CAD) (6–15%; 16 studies), 5% for peripheral arterial disease (PAD; 2–11%; 10 studies), and 10% for diabetic foot (4–26%; nine studies). Heterogeneity was extreme (I2 = 93.5–99.3%), and prediction intervals were wide. Excluding influential outliers left pooled estimates essentially similar but reduced τ2. In meta-regression, no moderator was significantly associated with retinopathy, stroke, or diabetic foot prevalence (all p > 0.05). For nephropathy, longer diabetes duration (β = −0.254, 95% CI −0.411 to −0.097, p = 0.005; 52.5% of between-study variance) and female proportion (β = 0.036, 95% CI 0.005 to 0.067, p = 0.026; 18.8%) were significant. For neuropathy, smoking prevalence was significant (β = 0.093, 95% CI 0.001 to 0.185, p = 0.047; 18.8%). For PAD, female proportion was inversely associated with prevalence (β = −0.084, 95% CI −0.147 to −0.021, p = 0.015; 53.2%). Region explained 84.5% of the heterogeneity in MI/CHD/CAD, with lower estimates in Tabuk and Taif, and HbA1c explained 24.5% of the heterogeneity in stroke (p = 0.167). Year of publication explained <10.0% of the heterogeneity in every parsimonious model. Substantial residual heterogeneity remained in all models (residual I2 83.0–99.9%). Individual studies also frequently reported associations of complications with poor glycemic control, longer diabetes duration, hypertension, dyslipidemia, obesity, smoking, and physical inactivity. Conclusions: Diabetes-related complications impose a substantial burden in Saudi adults with T2DM, but estimates vary markedly across populations, clinical settings, and diagnostic definitions. The findings support standardized screening and improved primary research using consistent case definitions; study-level meta-regression findings should be interpreted cautiously.

Diagnostics doi: 10.3390/diagnostics16203432

Authors: Ergun Mete Buket Başa Akdoğan Süleyman Utku Uzun Cemalettin Dost Zeyrek Feza Kırbıyık Ahmet Akçay

Background/Objectives: DNA methylation-based lymphocyte enumeration may provide an alternative to conventional immunophenotyping, but its associations with allergic phenotypes require careful interpretation. We examined these associations in a predominantly pediatric cohort. Methods: This retrospective study included 206 participants aged 1–57 years (189 aged <18 years; 57.8% male; median age 5 years, IQR 3–8), evaluated between 24 November 2025 and 28 February 2026. Absolute subset counts were derived from the epigenetic i.Mune TBNK assay and CBC lymphocyte counts. Group comparisons used Mann–Whitney U tests with Benjamini–Hochberg correction across 56 comparisons. Firth models adjusted for three subset counts, CD4/CD8 ratio, log(IgE+1), age, and sex; percentage-based, comorbidity-adjusted, and age-restricted sensitivity analyses were added. IgE-containing models included 201 complete cases. Results: Allergic rhinitis was associated with lower CD4+ counts in the primary model (OR per 100 cells/µL 0.923; p = 0.0009), with the association retained after comorbidity adjustment and age restriction but not in the percentage model. Atopic dermatitis was associated with log(IgE+1) (OR 1.475; p = 0.0009). Food allergy was associated with higher CD19+ counts in the primary model (OR per 100 cells/µL 1.060; p = 0.0341), but this association was not retained in sensitivity analyses. No absolute NK-count difference was found for food allergy. Single-marker discrimination was modest (CD4+ AUC for rhinitis 0.711). Conclusions: These exploratory associations are sensitive to the measurement scale and model specification. They do not establish phenotype-specific epigenetic mechanisms, standalone diagnostic utility, or functional immune monitoring.

Diagnostics doi: 10.3390/diagnostics16203431

Authors: Jocelyn Chu Wai Han Ma

I-131 scintigraphy can be performed after I-131 radioactive iodine (RAI) treatment in appropriate patients for dynamic risk stratification. Sodium iodide symporter (NIS) expression is a mechanism responsible for uptake of I-131 in thyroid tissue and thyroid cancer. There are other mechanisms that iodine engages in the body, leading to possible false-positive findings. A popliteal bursa, or Baker’s cyst, is a bursa that lies in the popliteal region. As a bursa, it is a potential space and is lined by synovial membrane. It is not normally visualized on imaging. However, passive diffusion of radioactive iodine or pathological changes occur with local irritation. Presented herein is a 75-year-old woman with a history of poorly differentiated thyroid carcinoma. Her postoperative American Thyroid Association risk stratification was high. A diagnostic iodine whole body scintigraphy for dynamic risk stratification following RAI treatment performed. Planar imaging on posterior-view showed mildly intense iodine uptake in the left knee, differentials included atypical location of osseous metastasis, and false-positive pathologies. Regional SPECT/CT localized the false-positive iodine uptake in the Baker’s cyst. The teaching point for this case is to be vigilant of uncommon false-positive pathologies on iodine scintigraphy. Diagnostic confidence is improved by adding SPECT/CT imaging.

Diagnostics doi: 10.3390/diagnostics16203430

Authors: Nebiha Gozde Ispir Gokalp Aslan Gulsun Akay

Background/Objectives: Artificial intelligence (AI) chatbots are increasingly used to obtain oral health information, yet prior dental studies have already evaluated overlapping domains such as accuracy, quality, readability, understandability, and actionability. This study applied and extended a multidimensional evaluation approach to compare AI-generated answers to dental patient questions, with emphasis on Turkish-language readability, standard PEMAT-P applicability, effect-size and uncertainty reporting, and inter-rater reliability. Methods: Thirty-three AI-assisted, expert-curated questions were submitted to ChatGPT 5.2, Gemini, DeepSeek V3, and Grok 3, yielding 132 responses. Three dental evaluators independently assessed clinical accuracy, Global Quality Score (GQS), understandability (PEMAT-U), and actionability (PEMAT-A). PEMAT-P scores were calculated using the standard item structure and item-specific applicability rules, with items coded as not applicable (N/A) excluded from the denominator. Readability was calculated using a deterministic, rule-based implementation of the Ateşman formula. Model comparisons used the Friedman test, Bonferroni-adjusted Wilcoxon signed-rank tests, effect sizes, bootstrap confidence intervals, and two-way random-effects intraclass correlation coefficients. An exploratory Pareto analysis assessed multidimensional dominance without imposing arbitrary weights. Results: Significant model differences were observed for all five dimensions (all p ≤ 0.002). Gemini had the highest mean GQS, clinical accuracy, PEMAT-U, and PEMAT-A scores, but its Ateşman readability score was significantly lower than those of ChatGPT, DeepSeek, and Grok. No significant readability differences were observed among the latter three models. Average-measure reliability was poor for GQS and clinical accuracy and moderate for PEMAT-U and PEMAT-A. No model dominated another across all five dimensions. Conclusions: The chatbots demonstrated model-specific strengths rather than uniform superiority. Their performance should be interpreted multidimensionally, together with effect magnitude, uncertainty, and inter-rater reliability, rather than through a single overall ranking.

Diagnostics doi: 10.3390/diagnostics16203429

Authors: Marcello Marchetta Lucio Giuseppe Granata Branislav Crnomarkovic Simona Giubilato Giuseppe Andò Mila Kovacevic

Artificial intelligence (AI) is being investigated across the acute coronary syndrome (ACS) care pathway, including early diagnosis, coronary lesion characterization, procedural guidance, and risk prediction. This comprehensive review examines the current evidence across the entire ACS trajectory, with particular emphasis on clinically actionable and interventional applications. AI-enabled electrocardiography (ECG) may improve detection of myocardial infarction, including occlusion myocardial infarction (OMI) that does not meet conventional STEMI criteria. Models combining clinical data and high-sensitivity troponin may improve early rule-out and rule-in. In coronary imaging, AI can quantify plaque characteristics and assist with the interpretation of OCT and IVUS, while image-derived physiology may help assess non-culprit lesions. However, better diagnostic accuracy does not necessarily translate into better revascularization decisions. AI-based models can also estimate post-ACS ischemic, bleeding, and mortality risk, although evidence that their use improves treatment or outcomes remains limited. The next priority is prospective evaluation of whether these tools improve decisions, workflow, and patient outcomes across diverse clinical settings.

Diagnostics doi: 10.3390/diagnostics16203428

Authors: Zainab Magaji Musa Habeeba Adamu Kakudi

Background: This systematic review aims to evaluate and synthesize the current research on generative artificial intelligence (AI) models, focusing on their roles, performance, datasets, and evaluation metrics in improving breast cancer detection. Method: A systematic search using the PRISMA guideline was conducted. Four electronic databases (Science Direct, IEEE Explore, SpringerLink, and Scopus) and Google Scholar were searched using specific search strings for online articles published between 2020 and 2024. After applying specified inclusion and exclusion criteria, 91 articles were selected for data extraction, synthesis, and quality assessment. Results: This study reveals that generative AI models are used in breast cancer diagnosis for data augmentation, classification, and segmentation. For data augmentation, GAN has proven to be of highest effectiveness, while transformers have the highest effectiveness in terms of classification and segmentation. This review highlights the growing adoption of various publicly and privately available datasets, which have played a crucial role in training and validating these models. The findings showed the importance of selecting appropriate datasets and metrics to enhance the effectiveness of generative AI models in breast cancer diagnosis. A notable gap identified is the underrepresentation of African populations in the datasets used. Furthermore, the limited applicability of these models in real-world clinical settings is attributed to the lack of explainability. Conclusions: This review provides valuable insights into current practices, identifies existing gaps, and highlights areas for future research, aiming to improve the reliability and applicability of AI-based diagnosis in clinical settings.

Diagnostics doi: 10.3390/diagnostics16203427

Authors: Jihyeon Jeon Hyunseung Ryu Myeongjin Lee Eun Hui Bae Soo Wan Kim Chang Seong Kim Se Hun Kim Young Joon Ki Dong Joon Kim Suhyung Park

Background/Objectives: Ultrasound-guided biopsy is essential for accurate needle placement in minimally invasive procedures. However, the limited availability of labeled medical data significantly constrains the development of needle segmentation models, and existing semi-supervised approaches rely solely on data-driven consistency constraints without incorporating domain-specific dynamic properties of the imaging process. We propose a semi-supervised unrolling optimization framework that combines dynamics-based data consistency with self-training. Methods: (1) A null-space projection-based Analytic Model (A) layer is unrolled into the network to suppress background interference and enforce dynamics-based constraints derived from temporal ultrasound sequences, in which the background subspace is estimated via singular value decomposition (SVD) of consecutive frames and the needle signal is recovered by projecting the observed image onto the orthogonal complement of this subspace. (2) A self-training strategy leverages unlabeled ultrasound data by generating soft pseudo-labels from a pretrained teacher network to iteratively supervise the student model, which shares the same unrolling architecture and is jointly trained with a supervised loss on labeled data and a pseudo loss on unlabeled data. Results: Evaluation on an ultrasound needle segmentation dataset demonstrated that the proposed method achieved a Dice score of 0.7429±0.0489 and an IoU of 0.5967±0.0917, outperforming the supervised UnrollNet baseline (Dice: 0.7298±0.0518), Co-Training (U-Net) (Dice: 0.6104±0.0949), and Meta Pseudo Labels (Dice: 0.6426±0.1140). The proposed method also yielded a mean trajectory angle error of 0.66∘±0.63∘ and a tip position error of 0.95mm±0.74mm. Conclusions: These results indicate the potential of the proposed framework for ultrasound-guided needle tracking.

Diagnostics doi: 10.3390/diagnostics16203426

Authors: Betül Demirciler Yavaş Sezgin Yılmaz

Background: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with limited survival despite advances in diagnosis and treatment. Dysregulation of apoptosis and tumor cell proliferation is a fundamental feature of cancer biology. M30, BCL-2, and BAX reflect different aspects of apoptotic activity and regulation, whereas Ki-67 is a widely used marker of cellular proliferation. However, the clinicopathological significance of these markers in PDAC remains incompletely characterized. This study aimed to evaluate the immunohistochemical expression of M30, BCL-2, BAX, and Ki-67 in PDAC and to investigate their associations with established clinicopathological features. Methods: This retrospective study included 50 patients with surgically resected PDAC treated at Afyon Kocatepe University Medical Faculty Hospital between January 2003 and May 2015. Archived tumor specimens were evaluated by immunohistochemistry for M30, BCL-2, BAX, and Ki-67. M30 and Ki-67 expression were quantified according to the percentage of positive tumor cells, while BCL-2 and BAX expression were assessed using semiquantitative staining scores based on staining intensity and the proportion of positive tumor cells. Immunohistochemical findings were compared with sex, tumor differentiation, tumor size, lymphovascular invasion, perineural invasion, surgical margin status, tumor stage, lymph node metastasis, and clinical stage. Results: The study cohort comprised 30 male and 20 female patients, with a mean age of 62.12 ± 10.93 years. M30 expression was detected in 39 (78%) cases, whereas Ki-67 expression ranged from 10% to 85% of tumor cells. BCL-2 and BAX expression showed variable staining patterns. None of the four markers demonstrated a statistically significant association with tumor differentiation, tumor size, lymphovascular invasion, perineural invasion, surgical margin status, tumor stage, lymph node metastasis, or clinical stage. Conclusions: In this cohort of surgically resected PDAC, immunohistochemical expression of M30, BCL-2, BAX, and Ki-67 was not significantly associated with conventional clinicopathological indicators of tumor aggressiveness. These findings indicate that immunohistochemical assessment of individual apoptosis- and proliferation-related markers may not adequately reflect tumor aggressiveness or clinicopathological heterogeneity in PDAC. Further studies incorporating larger cohorts, standardized immunohistochemical assessment, and clinical outcome data are warranted to clarify their potential biological and prognostic significance.

Diagnostics doi: 10.3390/diagnostics16203425

Authors: Yavuz Korkmaz İbrahim Miraç Eligüzel Adem Taha Özdemir

Background/Objectives: The Fagerström Test for Nicotine Dependence (FTND) is a subjective, self-report-based instrument used to grade the level of nicotine dependence. Complete blood count (CBC) parameters reflect markers of smoking-related systemic inflammation. In the present study, we aimed to develop a leakage-free and interpretable machine learning approach for classifying FTND level using demographic data, CBC parameters, and duration of smoking exposure. Methods: In this retrospectively designed study, the records of 660 patients with complete data who had presented to the Smoking Cessation Outpatient Clinic of Malatya Training and Research Hospital were included. Because one of the six FTND items directly scores the number of cigarettes smoked per day, the number of packs and the features related to it constitute data leakage and were therefore excluded from the data pool. Smoking duration (years), which is not an FTND item, was retained as the sole predictor of smoking exposure. Feature engineering generated 49 candidate features. Six base learners (logistic regression, random forest, gradient boosting, SVM, LightGBM, XGBoost) and a stacking ensemble were evaluated with an 80–20% training/test split and 10-fold stratified cross-validation. To prevent optimism bias, feature selection and scaling were performed only within the training folds, and class imbalance was addressed through class weighting. The models were interpreted with SHAP and LIME, and the contribution of each feature family was quantified by ablation analysis. Results: In leakage-free 10-fold cross-validation (the primary performance estimate), discrimination was modest, with the highest AUC (0.652) obtained by both SVM (RBF) and logistic regression; on the single hold-out test set, the stacking ensemble reached an AUC of 0.749 (95% CI 0.667–0.831). The full model did not significantly outperform smoking duration alone (DeLong p = 0.22), and extensive feature engineering did not provide a measurable gain (ΔAUC = −0.015). In the SHAP analysis, smoking duration and the age-based interaction terms made the largest predictive contributions. Conclusions: Routine CBC parameters do not by themselves constitute an independent diagnostic tool for determining dependence severity; they carry only weak, complementary information and should not be regarded as a screening biomarker. This exploratory study classifies FTND-based nicotine dependence severity at the individual patient level by combining CBC parameters with machine learning and explainable artificial intelligence; the model is not ready for clinical use.

Diagnostics doi: 10.3390/diagnostics16203424

Authors: Isra M. Alsaady

Intestinal parasitic infections remain a significant global public health concern, particularly in low- and middle-income countries, where timely and accurate diagnosis is essential for effective disease management and control. Although conventional diagnostic methods, including microscopy, antigen detection, and polymerase chain reaction (PCR), are widely used, each possesses inherent limitations related to sensitivity, turnaround time, laboratory infrastructure, or point-of-care applicability. Recent advances in clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated (Cas) systems have led to the development of highly sensitive and rapid molecular diagnostic platforms suitable for decentralized testing. This review summarizes current applications of CRISPR/Cas-based diagnostics for intestinal and foodborne parasitic infections, with particular emphasis on assays developed for Giardia duodenalis, Cryptosporidium parvum, Clonorchis sinensis, Fasciola hepatica, and Schistosoma spp. Published studies have predominantly employed Cas12a, with additional applications of Cas12b and Cas13a and, more recently, a type I-A Cascade–Cas3 system, generally coupled with isothermal amplification methods such as recombinase polymerase amplification (RPA) or recombinase-aided amplification (RAA), enabling highly sensitive detection within 60–90 min using fluorescence or lateral-flow strip readouts. The available evidence indicates high analytical sensitivity and specificity, with several assays demonstrating substantial agreement with conventional molecular methods and potential for point-of-care development. However, current CRISPR-based assays remain limited by dependence on nucleic acid extraction, relatively small clinical validation cohorts, lack of standardized protocols, and the persistence of false-negative results associated with low parasite burdens and pre-analytical variables. Emerging strategies, including simplified or extraction-free sample preparation, one-pot sample-to-answer platforms, and detection of parasite-derived cell-free DNA, may further enhance the clinical utility of CRISPR diagnostics. Overall, CRISPR/Cas-based technologies represent a promising next-generation approach for intestinal parasite diagnosis, although large-scale clinical validation and workflow optimization are still required before widespread implementation in routine clinical and field settings.

Diagnostics doi: 10.3390/diagnostics16203423

Authors: Aybike Bas Ozturk Gelengul Urvasizoglu Rama Abdulkader Nazrin Sariyeva Fatih Sengul

Background/Purpose: This study aimed to evaluate mandibular morphological, trabecular, dental, and periapical factors associated with favorable long-term outcomes following early mandibular first permanent molar (FPM) extraction. Methods: This retrospective study included 60 patients with pre-extraction and ≥5-year follow-up panoramic radiographs. Patients were classified into favorable (FO; n = 30) and unfavorable (UFO; n = 30) outcome groups according to residual space and second permanent molar (SPM) axial position. Gonial angle (GA), antegonial notch depth (AND), notch angle (ANA), cortical thickness (ACT), and corpus and angulus fractal dimensions (FD) were assessed. Initial SPM and second premolar (SP)angulations, primary second molar (PSM)–SP status, and FPM periapical index (PAI) scores were also evaluated. Analyses included Bonferroni correction, exploratory multivariable logistic regression, and receiver operating characteristic (ROC) analysis. Results: AND was greater in the FO group (Bonferroni-adjusted p = 0.015) and remained associated with FO after adjustment (OR = 2.22 per millimeter; 95% CI: 1.19–4.15; p = 0.012). An extracted PSM with an unerupted SP was associated with higher odds of FO than a retained PSM (adjusted OR = 9.51; 95% CI: 1.45–62.50; p = 0.019). AND demonstrated moderate discrimination (AUC = 0.728; 95% CI: 0.600–0.856); a ≥2.0-mm threshold yielded 86.7% sensitivity and 53.3% specificity. Other morphological and fractal parameters did not differ significantly between groups; angulations and PAI were not significantly associated with outcome. Conclusions: AND and PSM–SP status were associated with FO. These exploratory findings require validation in larger, independent cohorts before clinical application, particularly given the wide confidence intervals for categorical estimates and the limited specificity of the proposed AND threshold.

Diagnostics doi: 10.3390/diagnostics16203422

Authors: Alberto Vassallo Alessio Delfino Greta Ghizzardi Andrea Carbone Gloria Groppelli Gisella Boselli Noemi Busca Matteo Cerutti Sara Lodigiani Caterina Golinelli Guido Grignaffini Valeria Guazzoni

Background: Screening for diabetic retinopathy (DR) is resource-intensive. We evaluated the real-world diagnostic accuracy of the DAIRET® Artificial Intelligence (AI) algorithm, integrated into the electronic medical record, as a triage tool in routine diabetes care. Methods: Retrospective, STARD-AI-compliant study of consecutive adults with diabetes screened with non-mydriatic fundus photography between April and December 2025. The DAIRET® output (“suspected”/“not suspected”) was compared with grading by an ophthalmologist masked to the AI result. Sensitivity, specificity and predictive values with exact 95% confidence intervals were calculated for any DR and referable (moderate or worse) DR. Results: Among 1051 patients, 185 (17.6%) had DR: 160 mild and 25 moderate non-proliferative DR; none had severe DR. DAIRET® classified 271 patients (25.8%) as suspected. For any DR, sensitivity was 59.5% (52.0–66.6) and specificity 81.4% (78.7–83.9). For referable DR, sensitivity was 100.0% (86.3–100.0), specificity 76.0% (73.3–78.6) and negative predictive value 100.0% (99.5–100.0). Specificity was lower in patients aged <65 years and with type 1 diabetes. Conclusions: No referable case was missed, although sensitivity was based on 25 cases (lower limit 86.3%) and 15 AI-negative patients lacked complete verification. The 74% classified as “not suspected” is a potential, not measured, reduction in referrals. Performance for severe or proliferative DR could not be assessed, and multi-center confirmation is needed.

Diagnostics doi: 10.3390/diagnostics16203421

Authors: Yuanbin Li Yunyun Sun Weibin Chen Jing Fu

Background/Objectives: To evaluate the repeatability of the Swan SW600 optical biometer and its agreement with the Lenstar LS900 in measuring ocular biometric parameters in children and adolescents. Methods: This prospective study included 778 children and adolescents aged 3–18 years. Parameters included axial length (AL), corneal radii in the flattest and steepest meridians (R1 and R2), central corneal thickness (CCT), anterior chamber depth (AD), lens thickness (LT), white-to-white distance (WTW), and axial length-to-corneal radius ratio (AL/CR). Repeatability of Swan SW600 was assessed using within-subject standard deviation (Sw), coefficient of repeatability (CoR), coefficient of variation (CoV), and intraclass correlation coefficient (ICC). Agreement between devices was evaluated using paired t tests, ICC, and Bland–Altman analysis. Results: Swan SW600 repeatability was excellent for AL, R1, R2, CCT, AD, and AL/CR (ICC = 0.9918–0.9999) and lower for LT (ICC = 0.9060) and WTW (ICC = 0.8452). Agreement with Lenstar LS900 was strongest for AL (mean difference −0.050 ± 0.041 mm; 95% LoA −0.131 to 0.031 mm; ICC = 1.000), R1 (ICC = 0.986), R2 (ICC = 0.980), and AL/CR (ICC = 0.993). CCT and AD showed good agreement (ICC = 0.877 and 0.895), whereas LT showed lower agreement (ICC = 0.689). WTW showed poor agreement (ICC = 0.288). Age-stratified analyses showed consistently high agreement for AL, R1, R2, and AL/CR across all age groups, including children aged 3–6 years, whereas agreement for CCT, AD, LT, and WTW was more variable. Conclusions: The Swan SW600 demonstrates high repeatability and close agreement with the Lenstar LS900 for AL, corneal radii, and AL/CR in children and adolescents, including preschool-aged children; however, the weaker agreement observed for LT and particularly WTW suggests that these parameters should be interpreted with caution.

Diagnostics doi: 10.3390/diagnostics16203420

Authors: Luis Miguel Granja Villavicencio Andrea Estefanía Zurita Beltran Alex Bernardo Hugo Merino

Background and Clinical Significance: Indeterminate solid adnexal masses can remain difficult to characterize on conventional CT. Dual-layer spectral CT provides iodine concentration (IC), effective atomic number (Zeff), and electron density relative to water (EDW) from the same acquisition. We report a histopathologically confirmed primary ovarian leiomyoma and describe its regional multiphasic spectral behavior. Case Presentation: A 37-year-old woman presented with an O-RADS 4 solid right adnexal mass. Retrospective analysis sampled two enhancement-defined intralesional compartments across true noncontrast (TNC), arterial, venous, and delayed phases. On TNC images, ROI-A and ROI-B showed closely similar Zeff (7.39 vs. 7.37) and EDW (103.8% vs. 103.9%). ROI-A showed intense arterial enhancement (102.2 HU; IC 2.95 mg/mL; Zeff 8.78) followed by decline, whereas ROI-B showed low early enhancement and marked delayed fill-in, with delayed values slightly exceeding ROI-A (83.8 vs. 71.3 HU; IC 1.74 vs. 1.54 mg/mL; Zeff 8.25 vs. 8.16). Initial histopathology suggested fibroma; immunohistochemistry established ovarian leiomyoma. Conclusions: The two enhancement-defined compartments showed closely similar baseline spectral measurements but divergent postcontrast behavior. EDW demonstrated substantially lower-amplitude phase-related changes than IC and Zeff. These findings are descriptive and do not establish a diagnostic spectral signature or histologic specificity. When multiphasic dual-layer spectral CT has already been clinically acquired, regional spectral analysis may provide quantitative characterization of intralesional enhancement heterogeneity. In this case, however, spectral CT did not establish the diagnosis or alter management, and definitive diagnosis remained dependent on histopathology and immunohistochemistry.

Diagnostics doi: 10.3390/diagnostics16203419

Authors: Nandini Sharma Saurav Basu Mongjam Meghachandra Singh Mrunali Zode Shikha Taneja Malik Shivani Rao

Background: Anaemia is a major public health issue in India, where point-of-care testing is central to national control strategies. This study evaluated the diagnostic accuracy of the HemoCue® Hb 201+ for haemoglobin (Hb) estimation from capillary blood compared to the gold-standard venous blood analysis. Methods: In a cross-sectional study of 748 participants in a low-resource urban Delhi setting, Hb levels from single-drop capillary samples (HemoCue® Hb 201+) were compared to those from venous samples (automated autoanalyzer). Agreement was assessed using Bland–Altman analysis, Passing–Bablok regression, and standard diagnostic accuracy metrics. Results: The mean (SD) haemoglobin concentration was lower in capillary samples (11.83 [1.95] g/dL) than in venous samples (12.56 [1.89] g/dL). Capillary Hb was, on average, 0.73 g/dL lower than venous Hb (95% limits of agreement: −3.11 to 1.65 g/dL). Consequently, the HemoCue® Hb 201+ significantly overestimated anaemia prevalence (54.4% vs. 35.0%). The capillary method demonstrated high sensitivity (92.4%) for detecting anaemia but only moderate specificity (66.1%), indicating a tendency for false positives. Conclusions: Although the HemoCue® Hb 201+ is a sensitive tool for anaemia screening in field settings, the moderate specificity and the significant negative bias can lead to overestimation of prevalence and potential misclassification of individuals. However, the limitation of single-drop capillary sampling warrant cautious interpretation of results, particularly for clinical decision-making and precise prevalence estimation.

Diagnostics doi: 10.3390/diagnostics16203418

Authors: Kenji Tsuji Naruhiko Uchida Hiroyuki Nakanoh Yoshitaka Inoue Kazuhiko Fukushima Shinji Kitamura Jun Wada

Background/Objectives: Lower urine pH has been associated with reduced kidney function and increased risk of kidney disease, but its prognostic and pathological significance in biopsy-proven kidney disease remains unclear. Medullary cast formation has been shown to predict adverse renal outcomes beyond cortical interstitial fibrosis and tubular atrophy (IFTA), although its clinical determinants are not fully understood. We examined the associations of urine pH with kidney outcomes and medullary cast formation in patients undergoing native kidney biopsy. Methods: Among 1167 adults who underwent native kidney biopsy between 2011 and 2024, 503 patients with evaluable medullary tissue were included. Urine pH was analyzed in relation to clinical and histological variables and kidney outcomes. The primary outcome was a ≥40% decline in estimated glomerular filtration rate (eGFR) or initiation of renal replacement therapy. Results: Mean baseline eGFR was 60.7 ± 26.2 mL/min/1.73 m2 and urine pH was 6.15 ± 0.84. During a median follow-up of 2.11 years, 113 patients (22.5%) reached the outcome. Lower urine pH was associated with higher risk of kidney outcomes. In multivariable Cox models, urine pH remained independently associated with outcomes (hazard ratio per 1-unit increase, 0.69; 95% CI, 0.52–0.92). Addition of urine pH modestly improved discrimination (C-index 0.642 to 0.654; likelihood ratio test, p = 0.009). Lower urine pH was associated with greater medullary cast formation in unadjusted analysis. Conclusions: Lower urine pH was independently associated with adverse kidney outcomes and with greater medullary cast formation, suggesting that urine pH may reflect intratubular pathological changes associated with CKD progression.

Diagnostics doi: 10.3390/diagnostics16203417

Authors: Nathan Vishwanathan Jakob Wasserthal Shan Yang Martin Segeroth Joshy Cyriac Johanna Maria Lieb Michael Bach Marios Nikos Psychogios Matthias Anthony Mutke

Background: Age- and sex-specific CT reference percentile curves of ventricular volume may support objective assessment of ventricular enlargement. We aimed to generate such curves by combining a locally deployed large language model (LLM) for cohort curation with nnU-Net 12-subcompartment segmentation. Methods: This retrospective study did not require formal ethics approval under the Swiss Human Research Act. We screened 42,211 head CT reports from January 2019 to April 2024. A phrase prefilter identified 9622 candidates for German-tuned 70-billion-parameter LLM review of stroke, leukoencephalopathy, parenchymal defects, enlarged ventricles, and space-occupying lesions; 6516 remained. A second LLM workflow screened 210,761 clinical data warehouse summaries to exclude dementia, organic brain disease, or cognitive decline. After image-availability and series-mismatch exclusions, the final cohort comprised 2608 CTs from 2608 patients (1374 males, 1234 females; age 14–98 years). Ventricular masks were obtained using a validated nnU-Net tool integrated in TotalSegmentator. Results: LLM labelling accuracy in 471 blinded reports ranged from 0.966 to 0.992. CDW screening audit showed 91% agreement, sensitivity 0.96, and negative predictive value 0.96. Median total ventricular volume rose from 10.94 mL in young females and 13.42 mL in young males to 21.97 mL and 31.97 mL, respectively, in the 60–69 age group. Except for the fourth ventricle, compartments showed positive age correlations (r = 0.44–0.69); the fourth ventricle showed no relevant association (r = 0.01 males; r = 0.05 females). After adjustment for age, male sex remained associated with greater total ventricular volume (6.54 mL; 95% CI, 5.61–7.46; p<0.001). Conclusions: This study provides age- and sex-specific CT ventricular nomograms in a selected reference cohort. The LLM-assisted curation and nnU-Net segmentation workflow provides a feasible approach for large-scale cohort analysis.

Diagnostics doi: 10.3390/diagnostics16203416

Authors: Anna Russo Vittorio Patanè Annalisa Di Maio Lucrezia Bucciero Renato Franco Teresa Troiani Giuseppe Argenziano Alfonso Reginelli

Background: Ultra-high-frequency ultrasound (UHFUS) provides high-resolution assessment of superficial skin lesions, but evidence in melanoma has largely focused on preoperative thickness estimation. We evaluated the reproducibility of a structured UHFUS assessment and its histopathologic concordance in primary cutaneous melanoma. Methods: This single-center retrospective study included 320 treatment-naïve, histologically confirmed primary cutaneous melanomas examined with UHFUS (48–70 MHz) before excision. Two experienced radiologists independently assessed tumor thickness, horizontal diameter, surface discontinuity, deepest involved compartment, boundary definition, morphology, echostructure, and separate perilesional hypoechoic foci. Histopathology served as the reference standard. Reproducibility was assessed using ICC and κ statistics; UHFUS–Breslow agreement was evaluated using Lin’s concordance correlation coefficient (CCC) and Bland–Altman analysis. Results: Interobserver reproducibility was excellent for tumor thickness (ICC 0.96; 95% CI, 0.95–0.97) and horizontal diameter (ICC 0.94; 95% CI, 0.92–0.95). UHFUS thickness showed excellent concordance with Breslow thickness (CCC 0.95; 95% CI, 0.94–0.96 for both readers), with small positive biases (+0.12 and +0.10 mm). Exact agreement across predefined thickness strata was 90.0%. Surface discontinuity showed high sensitivity and specificity for histopathologic ulceration, whereas perilesional hypoechoic foci were highly specific but moderately sensitive for microsatellitosis. Increased tumor-infiltrating lymphocytes and an associated nevus component independently predicted greater UHFUS overestimation. Conclusions: Structured UHFUS provides reproducible quantitative and qualitative preoperative assessment of primary melanoma beyond thickness alone and may serve as a complementary imaging tool within specialized multidisciplinary pathways, while histopathology remains the reference standard for definitive diagnosis and staging.

Diagnostics doi: 10.3390/diagnostics16203415

Authors: Liora Colobatiu Romolica Mihaiu Alexandra Pusta Simona Mirel

Continuous glucose monitoring (CGM) has evolved beyond conventional diabetes management into an enabling technology for metabolic phenotyping and precision nutrition by providing continuous, real-world assessment of individual glycemic responses to dietary and lifestyle exposures. This narrative review examines the principles and clinical utility of CGM and its emerging applications in metabolic monitoring and personalized nutrition, with particular emphasis on postprandial glycemic variability, computational prediction, dietary feedback, and behavioral interventions. A literature search was conducted in Web of Science, PubMed, Scopus, and Google Scholar using predefined combinations of terms related to CGM, precision and personalized nutrition, diet, postprandial glycemic responses, lifestyle, glycemic variability, artificial intelligence, machine learning, and computational nutrition, including English-language literature available up to June 2026. Current evidence demonstrates substantial interindividual variability in postprandial glycemic responses and supports the potential integration of CGM with dietary, clinical, anthropometric, behavioral, and microbiome-derived data to characterize individual metabolic responses and inform individualized prediction and nutritional guidance. However, the reproducibility and generalizability of CGM-derived metabolic phenotypes and predictive models remain incompletely established. CGM-supported nutritional and behavioral interventions have demonstrated improvements in glycemic and selected cardiometabolic outcomes, particularly in individuals with type 2 diabetes, whereas evidence of clinical benefit in populations without diabetes remains substantially more limited. Sustained engagement and psychological, technical, and accessibility-related limitations also remain important considerations. Emerging multi-analyte sensing technologies may further broaden continuous metabolic assessment and support more comprehensive, data-driven precision-nutrition strategies.

Diagnostics doi: 10.3390/diagnostics16203414

Authors: Jang Woo Ha Oh Chan Kwon Yong-Beom Park Sang-Won Lee

Background/Objectives: The age item of the 2022 American College of Rheumatology (ACR) and the European Alliance of Associations for Rheumatology (EULAR) criteria for Takayasu arteritis (TAK) (the 2022 ACR/EULAR criteria) limits the reclassification of TAK among patients aged over 61 who were classified as TAK according to the 1990 ACR criteria. Therefore, we evaluated the clinical significance of the age item of the 2022 ACR/EULAR criteria. Methods: We included 22 previously TAK-diagnosed patients aged over 61 (TAK patient aged >61 years) and 41 TAK-reclassified patients aged 50–60 (controls) in this study and retrospectively reviewed their medical records. We compared the satisfied items of the 2022 ACR/EULAR criteria between the two groups and further investigated whether these 22 TAK patients aged >61 years fulfilled the criteria for other relevant diseases. Results: In terms of absolute requirements, TAK patients aged >61 years were significantly older than TAK-reclassified patients aged 50–60. However, there were no further significant differences in the additional clinical and imaging criteria between the two groups. TAK patients aged >61 years exhibited a significantly higher frequency of ascending aorta involvement than TAK-reclassified patients aged 50–60 (18.2% vs. 0%, p = 0.012). Among the 22 TAK patients aged >61 years, ten were categorized as clinically isolated aortitis, and three of the ten patients with CIA could additionally be categorized as restrictively defined-isolated aortitis. Conclusions: Our findings support the need for external validation of the current age threshold in larger cohorts from different ethnic and geographical populations.

Diagnostics doi: 10.3390/diagnostics16203413

Authors: Ilkay Sibel Kervancı Gözde Özsert Yiğit

Background: Accurate identification of EGFR-mutant, KRAS-mutant, and triple-negative (TN) LUAD driver mutation subtypes is essential for guiding targeted therapy, yet standard molecular testing is invasive and not always feasible. Gene expression-based machine learning offers an alternative that avoids additional invasive sampling; however, existing models are largely restricted to binary classification and lack cross-platform generalizability. Methods: We developed a multi-cohort, ComBat-harmonized pipeline integrating SHAP-driven feature selection and a Bayesian-optimized heterogeneous ensemble of five learners, extended with NSGA-II Pareto-optimal weight optimization under leak-free cross-validation. External validation used an independent RNA-seq cohort with reference-batch harmonization and threshold calibration. Results: ParetoVoting achieved the best internal performance (F1-macro = 0.736, AUROC = 0.877), statistically indistinguishable from SoftVoting (F1-macro = 0.735; Cliff’s δ=−0.12), which was carried forward for external validation.On TCGA-LUAD (n=508), SoftVoting attained F1-macro = 0.700 and AUROC = 0.850, though this reflects an out-of-range KRAS threshold (representative value ∼0.66–0.68). Ablation analysis showed components contributed unequally within internal cross-validation, with ComBat’s critical role instead emerging during cross-platform external generalization. SHAP analysis identified biologically coherent signatures consistent with known LUAD oncogenic signaling. Conclusions: This framework provides a reproducible, cross-platform approach to three-class driver mutation subtyping from transcriptomic data, offering benchmarks for this underexplored task and potential clinical utility where tissue-based profiling is infeasible.

Diagnostics doi: 10.3390/diagnostics16203410

Authors: Vyacheslav Beloussov Vitaliy Strochkov Nurlan Sandybayev Alyona Lavrinenko Talgat Aitpenov Maxim Solomadin

Background/Objectives: Sepsis is characterized by systemic immune dysregulation and organ dysfunction, but transcriptomic profiles from different biofluids may provide partially overlapping and distinct molecular readouts of the host response. We characterized transcriptomic profiles of whole blood and urinary cellular fractions in sepsis, with particular emphasis on a urinary transcriptional gradient associated with continuous serum creatinine and on whether this association was mirrored in matched blood. Methods: Targeted RNA sequencing was performed on whole blood from 35 patients with sepsis and 10 healthy controls and on urinary cellular fractions from 21 patients with sepsis and 7 controls using the Ion AmpliSeq Transcriptome Human Gene Expression workflow. Differential expression was assessed with DESeq2, with sequencing-adjusted sensitivity models where appropriate. Sensitivity analyses addressed the highest creatinine value, sex and age, and matched blood–urine creatinine-associated effects. Results: Whole-blood analysis identified 2659 differentially expressed genes (DEGs), including a robust core of 1796 genes characterized by neutrophil–myeloid activation and adaptive-immune suppression. The exploratory urine case–control comparison identified 1552 DEGs but was substantially confounded by sequencing chip. Continuous serum creatinine analysis identified 4064 chip-adjusted urinary DEGs, including a robust core of 3774 genes enriched for inflammatory, interferon, hypoxic, autophagic, lysosomal, vesicular, metabolic, and mitochondrial programs. Exclusion of the highest creatinine sample retained 3192/4064 strict DEGs with the same direction and 2926/3774 robust-core genes. In the same 21 patients, adjusted creatinine-associated effects were weakly concordant between blood and urine at the gene level (Pearson r = 0.192; Spearman ρ = 0.199), with five overlapping strict DEGs and no robust-core overlap. Hallmark concordance was greater but moderate (Pearson r = 0.293; Spearman ρ = 0.464), with 14 shared robust pathways. Conclusions: Transcriptomic profiles of whole blood and urinary cellular fractions showed distinct but partially overlapping host-response patterns in sepsis. The serum creatinine-associated urinary transcriptional axis was robust across sensitivity analyses and was only weakly mirrored at the gene level in matched blood, despite partial pathway-level convergence. These findings should be interpreted as serum creatinine-associated transcriptional patterns rather than as evidence of kidney-specific injury or validated diagnostic or prognostic signatures. Independent longitudinal cohorts and orthogonal molecular validation are required.

Diagnostics doi: 10.3390/diagnostics16203412

Authors: Michael Y. Zhu Sejal D. Patel Nikki Daniels John Hsu Rachel D’Cunha Alex Choi Alice Haystead Stephanie J. Chiu Burton Scott Dilraj S. Grewal Sharon Fekrat

Background/Objectives: Characterization of individual retinal layer thicknesses in mild-to-moderate Parkinson’s disease (PD) remains limited. This study compares retinal layer thicknesses between patients with mild-to-moderate PD and controls. Methods: In this cross-sectional study, patients with PD of Hoehn and Yahr (HY) stage 1 to stage 3 and age- and sex-matched cognitively normal controls without PD underwent spectral-domain optical coherence tomography (OCT) imaging. Seven retinal layers were segmented: nerve fiber layer, ganglion cell–inner plexiform layer (GC-IPL), inner nuclear layer (INL), outer plexiform layer, outer nuclear layer (ONL), photoreceptor layer (PRL), and retinal pigment epithelium (RPE). Mean thickness for each layer and the total retina were measured within the 3 mm and 6 mm Early Treatment Diabetic Retinopathy Study rings. Results: Sixty-seven eyes from 41 patients with PD and 72 eyes from 41 controls were included. In the 6 mm ring, PD eyes had a nominally thicker GC-IPL (p = 0.01), INL (p = 0.01), RPE (p = 0.03), and total retina (p = 0.03) compared to control eyes. In the 6 mm ring, PRL was nominally thinner in HY stage 3 compared to HY stages 2–2.5 (p = 0.02). In the 6 mm ring, the ONL was nominally thinner in the eyes of PD patients in HY stage 3 compared to the eyes of PD patients in HY stages 1–1.5 (p = 0.02) and 2–2.5 (p = 0.04). However, none of these differences remained significant after False Discovery Rate adjustment (all adjusted p > 0.05). Conclusions: In this exploratory cross-sectional study, no significant differences in macular retinal layer thicknesses were found between patients with mild-to-moderate PD and controls without PD after adjusting for multiple comparisons. The nominal thickness differences observed here require larger, longitudinal cohorts to determine if true structural differences exist in mild-to-moderate PD.

Diagnostics doi: 10.3390/diagnostics16203411

Authors: Jianhua Mu Yi Luo Han Liu Xuanhong He Minxun Lu Fan Tang Yitian Wang Yong Zhou Li Min Chongqi Tu

Background: Stage IIB conventional osteosarcoma exhibits highly heterogeneous responses to neoadjuvant chemotherapy, necessitating reliable, noninvasive pre-treatment evaluation systems. Methods: This retrospective study of 198 patients utilized pre-treatment T2-weighted magnetic resonance imaging (MRI) and baseline clinical data. Twelve classical convolutional neural network architectures were benchmarked to identify the optimal imaging backbone. This selected radiomics score was then integrated with core clinical variables using logistic regression to construct a multimodal model. Gradient-weighted Class Activation Mapping++ (Grad-CAM++) and SHapley Additive exPlanations (SHAP) algorithms provided image- and feature-level interpretability. Results: DenseNet121 achieved the highest mean cross-validated area under the curve (AUC; 0.775) and was selected, with AUCs of 0.797 (95% CI: 0.716–0.877) and 0.701 (95% CI: 0.513–0.877) in the training and test cohorts. Adding the clinical variables improved discrimination, yielding a test-cohort AUC of 0.827 (95% CI: 0.661–0.992) with significant reclassification gain over the radiomics-only model (NRI = 1.28, IDI = 0.177; DeLong p = 0.011). Grad-CAM++ activation concentrated on the solid medullary and extraosseous soft-tissue components, and SHAP ranked the radiomics score as the strongest contributor. Conclusions: Integrating deep learning radiomics with key clinical features provides a noninvasive tool for the individualized prediction of neoadjuvant chemosensitivity in osteosarcoma.

Diagnostics doi: 10.3390/diagnostics16203409

Authors: Jakub Jankowski Natalia Maślanek Marcin Glin Marcin Jasiewicz Agnieszka Pawełczyk Michał Polguj Maciej Radek

Background/Objectives: Vertebral numbering on limited lumbosacral imaging is difficult when the thoracic or lumbar count varies. The L3 transverse process has been proposed as a landmark because it is often the longest, but this has not been tested across segmentation patterns. This study assessed whether L3 as the level bearing the longest transverse process is independent of thoracic and lumbar vertebral count on whole-spine CT. Methods: Of 499 trauma CT examinations with confirmed numbering, all 49 non-standard thoracolumbar formulas were included, together with 17 C7T12L5 spines that remained after exclusion of transitional and numerical anomalies at every level (n = 66). Bilateral lumbar transverse-process lengths were measured on multiplanar reconstructions. The longest level was identified by morphological and presacral numbering. Associations with thoracic patterns (C7T11, n = 10; C7T12, n = 43; C7T13, n = 13) were tested with the Fisher–Freeman–Halton exact test and Monte Carlo simulation. Nine primary analyses were adjusted with the Holm procedure. Inter-observer agreement was assessed with an intraclass correlation coefficient. Results: In this enriched cohort, L3 was the longest level in 45/66 cases (68.2%) based on the single longest transverse process and 49/66 (74.2%) based on bilateral mean length. These percentages are not population prevalences. Within the C7T12 group, the corresponding proportions were 76.7% and 83.7%, respectively. By bilateral mean length, L3 was longest in 30.0% of C7T11, 83.7% of C7T12 and 76.9% of C7T13 cases (exact p = 0.003, Holm-adjusted p = 0.014). The single-process association did not remain significant after Holm correction (adjusted p = 0.058). The 22nd presacral vertebra showed a comparable dependence on thoracic pattern (Holm-adjusted p = 0.041 and 0.001 for the single-process and bilateral-mean analyses, respectively). Inter-observer ICC was 0.88 for individual transverse-process lengths and 0.93 for bilateral means. Conclusions: Neither L3 nor the 22nd presacral vertebra is a segmentation-independent marker of lumbar identity. Full-spine counting remains necessary when precise numbering is required.

Diagnostics doi: 10.3390/diagnostics16203408

Authors: Gino Nicolas Algarra-Tavera Angie Jimena Páramo-Cipagauta Andrea Marisol Moreno-Gonzalez Addy Cecilia Helguera-Repetto Claudia Andrea Cruz-Baquero

Background: Syphilis remains a relevant public health problem and continues to be associated with adverse perinatal outcomes. In newborns, conventional serological tests are often difficult to interpret due to maternal antibody transfer and the immaturity of the neonatal immune response. These limitations have led to increasing interest in molecular approaches as complementary diagnostic tools. Methods: This pilot study compared two real-time PCR methodologies for detecting Treponema pallidum DNA in umbilical cord blood: a SYBR Green-based qPCR targeting the polA gene and a TaqMan probe-based qPCR targeting the TpN47 gene. Thirty samples from neonates born to mothers with suspected gestational syphilis were analyzed under standardized conditions. Analytical performance and reproducibility were evaluated before application to clinical samples. Results: Both assays showed stable amplification and acceptable reproducibility. During standardization, the TaqMan assay reached a lower detection limit. However, when applied to clinical samples, the SYBR Green approach identified more positive cases (10/30 vs. 4/30), highlighting differences between analytical performance and behavior in clinical samples. Conclusions: Both methods were suitable for molecular detection of T. pallidum. However, their performance differed in neonatal samples, indicating that analytical sensitivity alone may not predict clinical detection capacity. Molecular testing in cord blood may provide complementary information when serological results are inconclusive.

Diagnostics doi: 10.3390/diagnostics16203407

Authors: K. R. Saranya Y. Suganya

Background/Objectives: Brain tumor classification from magnetic resonance imaging (MRI) has been significantly improved through deep learning techniques; however, the lack of interpretability remains a major challenge for clinical adoption. Methods: This study proposes an explainable artificial intelligence (XAI)-driven framework for multiclass brain tumor classification using a baseline convolutional neural network (CNN) and four transfer learning models, namely ResNet50, DenseNet121, MobileNetV2, and EfficientNetB0. The models were trained and evaluated on a publicly available brain MRI dataset consisting of glioma, meningioma, and pituitary tumor classes. Their classification performance was assessed using accuracy, precision, recall, F1-score, receiver operating characteristic area under the curve (ROC-AUC), and confusion matrix analysis. To enhance transparency and interpretability, Grad-CAM, LIME, and SHAP were used to visualize and quantify the regions contributing to the classification decisions. Results: Experimental results state that the transfer learning models consistently outperformed the CNN by learning more discriminative feature representations while producing more localized and interpretable explanations. The agreement among Grad-CAM, LIME, and SHAP confirms that the proposed models predominantly relied on tumor regions rather than irrelevant background information, thereby improving the interpretability and reliability of the diagnostic predictions. Conclusions: The proposed framework provides an effective and explainable computer-aided diagnosis system that supports trustworthy deep learning-based brain tumor classification and has the potential for decision-making.

Diagnostics doi: 10.3390/diagnostics16203405

Authors: Yiao Di Chang Geng Siyuan Fan Chao Chen Min Lang Wei Zhang Daobin Zhou Yan Zhang

Objective: Neurological involvement in intravascular large B-cell lymphoma (IVLBCL) is heterogeneous, prompting us to characterize its diverse manifestations through an integrated clinical and neuroimaging framework. Methods: This single-center retrospective study included 55 patients with pathologically confirmed IVLBCL diagnosed at Peking Union Medical College Hospital between January 2015 and June 2023. Pretreatment neurological involvement was identified in 29 patients based on attributable clinical and/or imaging findings after exclusion of more plausible alternative causes. Patterns were assigned primarily by clinical manifestations, supported by available imaging. Results: Six potentially overlapping clinicoradiologic patterns were identified. The stroke-like pattern (n= 5) comprised acute focal deficits with corresponding infarct-like or ischemic lesions. The encephalopathy pattern (n= 11) included cognitive decline, behavioral changes, impaired consciousness, and/or seizures, with or without infarct-like lesions or white matter hyperintensities. Three patients developed encephalopathic features following stroke-like presentations, including one with concomitant myelopathy. The mass-like pattern (n= 1) presented with headache and vomiting associated with enhancing lesions and surrounding edema. Myelopathy (n= 3) was characterized by lower-limb weakness with spinal cord-localizing signs, whereas radiculoneuropathy (n= 5) manifested as bilateral lumbosacral nerve-root involvement with weakness, sensory abnormalities, and reduced reflexes. Corresponding MRI abnormalities were absent in two patients with encephalopathy and one with myelopathy. The asymptomatic pattern (n= 8) comprised patients with imaging abnormalities but no neurological symptoms or signs. A total of 19 of 22 patients evaluable for treatment response achieved complete remission. Conclusions: Neurological involvement in IVLBCL comprises overlapping and evolving clinicoradiologic presentations, with variable correspondence between symptoms and imaging findings. This descriptive framework may help clinicians recognize its diverse manifestations and consider IVLBCL when the clinical course or imaging findings remain insufficiently explained.

Diagnostics doi: 10.3390/diagnostics16203406

Authors: Muhammad Kabir Abdullahi Sarina Mansor Mohammad Faizal Ahmad Fauzi

Background/Objectives: Deep convolutional neural networks achieve strong histopathological image-classification performance but often require substantial computational resources. This study proposes DSR-VGG, a lightweight Depthwise Separable Residual VGG architecture for nasopharyngeal histopathological image classification. Methods: DSR-VGG comprises six Depthwise Separable Blocks with residual projection shortcuts, global average pooling, dropout regularization, and a classification layer. An inverse-frequency weighted random sampling strategy was used to address severe class imbalance. The primary evaluation used 88,002 nasopharyngeal histopathology patches from four classes: Normal, lymphoid hyperplasia, nasopharyngeal inflammation, and nasopharyngeal carcinoma. Training was repeated using three random seeds, with supplementary public datasets used to assess cross-dataset architectural robustness. Results: Across three runs, DSR-VGG achieved 99.764 ± 0.049% accuracy, 99.070 ± 0.365% balanced accuracy, and 99.219 ± 0.215% macro-F1. The model contained only 0.528 million parameters, required approximately 0.31 GFLOPs, and achieved 2.38 ms single-image inference latency under the stated GPU benchmarking conditions. Although several baseline architectures achieved marginally higher accuracy, DSR-VGG maintained competitive predictive performance with substantially lower computational complexity. Conclusions: DSR-VGG provides a favorable accuracy–complexity trade-off for histopathological patch classification. However, patient-/WSI-disjoint evaluation, independent multi-center validation, and whole-slide assessment remain necessary before clinical deployment.

Diagnostics doi: 10.3390/diagnostics16203404

Authors: Meis Jawad Yasmin Soltanzadeh-Naderi Talha Butt Stefan Acosta

Background: Acute mesenteric ischaemia (AMI) includes acute superior mesenteric artery (SMA) thrombosis and embolism, venous AMI, and non-occlusive mesenteric ischaemia (NOMI). Patients with AMI are identified using the International Classification of Diseases (tenth revision (ICD-10)) code K55.0 (acute vascular disorders of the intestine). Reporting of outcomes depends on reliable case identification. Methods: A retrospective review of all patients assigned with ICD-10 code K55.0 at a tertiary university hospital between 1st January 2023 and 31st December 2025 was performed. Medical records and imaging findings were scrutinized to validate the diagnosis. Results: Among 218 patients assigned ICD-10 code K55.0, 117 (53.7%) had confirmed AMI and 198 (90.8%) had acute gastrointestinal ischaemia. Patients with NOMI (n = 30, 53.3%) had a higher bowel resection rate than patients with embolic SMA occlusion (n = 21, 23.8%; p = 0.039) or venous AMI (n = 15, 6.7%; p = 0.012). The in-hospital mortality rate was lower in patients with venous AMI (6.7%) than in patients with NOMI (66.7%; p < 0.003) or thromboembolic SMA occlusion (42.9%; p = 0.015). Conclusions: The positive predictive value for AMI using ICD-10 code K55.0 was 53.7%, underscoring the need for validated case identification. The heterogeneity of diagnoses captured by this code supports consideration of a more granular ICD coding system. A conceptual proposal is presented for further discussion and validation.

Diagnostics doi: 10.3390/diagnostics16203403

Authors: Kübra Okuyucu Aybike Şenel Ahmet Gülünay Murat Yücel

Background and Objective: Spinal pain is highly prevalent, yet clinically accessible tools for pain quantification remain limited. This study evaluated whether machine learning (ML) algorithms using StimaWELL 120MTRS-derived scores alongside demographic variables can predict self-reported spinal pain intensity and compared their performance against linear mixed model (LMM)-based associations. Methods: Seventy-eight adults with spinal pain (44 female, 34 male; mean age 43.08 ± 11.50 years) were assessed under two electrode configurations: opposing electrode (OE) and adjacent electrode (AE). Self-reported pain was measured using the Numeric Pain Rating Scale (NPRS). Repeated measures correlation, intraclass correlation coefficients (ICC), LMM, and eight ML algorithms were applied to evaluate predictive capacity. Results: Repeated measures correlations between StimaWELL scores and NPRS were negligible and non-significant (OE: r = −0.003, p = 0.970; AE: r = 0.015, p = 0.876), with ICC values indicating poor agreement (OE: 0.364; AE: 0.452). LMM revealed no statistically significant fixed effects for either configuration. Despite this, ML algorithms achieved moderate predictive performance, with Extra Trees and CatBoost yielding the highest tolerance-based accuracy (up to 73–74% for AE-based models). The AE StimaWELL score was the dominant predictor across feature importance analyses, followed by body weight and height. Conclusions: ML algorithms extracted the predictive signal from StimaWELL 120MTRS data where LMM found none, highlighting nonlinear relationships between device-derived scores and pain intensity. AE configuration demonstrated superior predictive performance. These findings suggest that StimaWELL 120MTRS may provide complementary quantitative information in spinal pain assessment, pending external validation in larger, diverse populations.

Diagnostics doi: 10.3390/diagnostics16203402

Authors: Boyu Zhang Yu Zhang Yaqin Wu Yue Gao Xingxing Li Han Wu Yang Li Ning Song

Background and Clinical Significance: The role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) in visceral leishmaniasis (VL) remains undefined. We sought to characterize the PET/CT features of VL and assess its diagnostic and therapeutic value. Case Presentation: Four VL patients undergoing PET/CT at our hospital (2022–2025) were retrospectively analyzed as a single-center case series, combined with a literature review of published VL PET/CT cases up to December 2025. Three of the four cases exhibited increased 18F-fluorodeoxyglucose (18F-FDG) uptake in the spleen, bone marrow, and lymph nodes, with additional tonsillar uptake in one case and hepatic uptake in another; one case presented with isolated lymph node uptake. In three cases, initial bone marrow smears were negative for amastigotes, and PET/CT was performed for fever of unknown origin (FUO). One case was diagnosed within one week via metagenomic next-generation sequencing (mNGS) prompted by PET/CT and epidemiological history. In the other two, VL was not suspected; they received chemotherapy/corticosteroids for presumed hemophagocytic syndrome (HPS) or connective tissue disease, and the time from symptom onset to VL diagnosis ranged from 2.5 to 4.5 months. The fourth case, confirmed by bone marrow smear, underwent PET/CT for suboptimal treatment response to exclude other diseases. Among 99 published VL cases undergoing PET/CT, indications were documented in 35, with FUO representing 83%. Initial bone marrow smears were negative in 69% of 64 evaluable cases. Of the 88 cases with evaluable PET/CT findings, 5 showed no abnormal FDG uptake. The predominant pattern was increased 18F-FDG uptake in the reticuloendothelial system (RES), most frequently involving the spleen (73/88, 83%), bone marrow (44/88, 50%), lymph nodes (29/88, 33%), and liver (15/88, 17%); other sites (lungs/pleura, colon, tonsils) were rarely involved. Accompanying enlargement of the spleen or liver was seen in approximately 50% of cases. The most common involvement patterns were combined splenic and bone marrow (23/88, 26%) and isolated splenic (20/88, 23%). Conclusions: PET/CT can provide diagnostic clues for VL, screen for comorbidities, and guide biopsy. Typical PET/CT findings—increased RES uptake without significant other organ involvement—reflect the parasite’s RES tropism. However, these findings mimic lymphoma, HPS, hematological disorders, and connective tissue diseases, risking misdiagnosis. Thus, VL should be promptly excluded in such patients using epidemiological history and etiological testing before considering alternative diagnoses.

Diagnostics doi: 10.3390/diagnostics16203401

Authors: Miodrag Djordjevic Aleksandar Karanikolic Ljubinka Velickovic

Background/Objectives: Breast cancer (BC) is the most common cancer in women worldwide and has a high mortality rate; thus, it is essential to determine the relevance of not only standard clinicopathological parameters, but also non-standard parameters, such as cancer stem cell molecular markers CD44 and CD117. These factors could possibly be used to predict cancer aggressiveness and metastasis. The present study aimed to evaluate the significance of CD44 and CD117 expression/co-expression in relation to clinicopathological parameters, molecular cancer subtypes, and axillary lymph node (ALN) status in invasive ductal cancer (IDC) of the breast. Methods: The investigation included 136 patients with IDC in whom radical mastectomy had been performed. The level of CD44 and CD117 expression in cancer tissue (high or low) was determined via immunohistochemical analysis. Results: High CD117 expression and CD44/CD117 co-expression were closely linked to a higher Ki-67 index (p < 0.001; p = 0.003, respectively) and triple-negative breast cancer (TNBC) (p < 0.001; p < 0.001, respectively). Multivariate linear regression analysis revealed that CD44/CD117 co-expression was independently associated with a higher number (p < 0.001), as well as a higher percentage (p = 0.005) of metastatic ALNs. Conclusions: This study showed that CD44/CD117 co-expression is an independent predictor of a higher number and percentage of metastatic ALNs in IDC and may have potential prognostic value.

Diagnostics doi: 10.3390/diagnostics16203400

Authors: Sung-Lin Hu Hsiang-Lin Lee Ming-Yu Lien Edie-Rosmin Wu Xiu-Yuan He Shun-Fa Yang Chih-Hsin Tang

Background: Hepatocellular carcinoma (HCC) is the most commonly diagnosed cancer type worldwide in males and the ninth among females, and it is a primary cause of cancer-associated death. The adipokine nesfatin-1, initially discovered in hypothalamic neurons, is produced by the precursor NUCB2 gene. The relationship between NUCB2 polymorphisms, behavioral risk factors that facilitate cancer, and HCC is still unknown. Methods: Four NUCB2 genetic polymorphisms were investigated in 822 normal controls and 411 patients with HCC using qPCR. The GTEx portal was used to assess the association between NUCB2 genetic variants and expression. NUCB2 levels in patients with HCC were evaluated using TCGA data. Results: Relative to the wild-type GG genotype, the AA genotype at the NUCB2 SNP rs214101 was associated with an augmented risk of distant metastasis and vascular invasion. The GA and AA genotypes at rs214101 were also associated with an increased likelihood of vascular invasion among smoking HCC patients compared to those carrying the GG genotype. Notably, GTEx data uncovered that the AA homozygous genotype was correlated with remarkably higher NUCB2 levels than those observed in individuals with the rs214101 GG genotype in lymphocytes and whole blood samples. TCGA data revealed that HCC patients exhibited higher NUCB2 expression in tumorous compared to non-tumorous liver tissue. Conclusions: NUCB2 SNP rs214101 may be associated with HCC progression and metastasis.

Diagnostics doi: 10.3390/diagnostics16203399

Authors: Adnan Çelikel Ümit Şimşek Kenan Karbeyaz Alper Özkök

Background/Objectives: Upper extremity fractures in older adults may cause lasting disability, but radiologic characteristics associated with permanent functional impairment in medicolegal populations remain unclear. We described these injuries and examined associated factors. Methods: Of the 94 initially identified patients, seven with unavailable follow-up examination records were excluded. This single-center retrospective cohort included 87 medicolegal patients aged ≥65 years with 104 radiographically confirmed upper extremity fractures evaluated between 2015 and 2024. The outcome was permanent functional impairment documented in a definitive medicolegal report after clinically appropriate follow-up. An exploratory, clinically selected logistic regression model included age, multiple fractures, displacement, and intra-articular extension. Results: Median age was 70 years, 70.1% were men, and interpersonal violence was the most frequent mechanism (51.7%). Permanent functional impairment was identified in 35 patients (40.2%; 95% CI, 30.6–50.7). Multiple upper extremity fractures (aOR, 3.79; 95% CI, 1.01–14.25), at least one displaced fracture (aOR, 4.52; 95% CI, 1.30–15.73), and at least one intra-articular fracture (aOR, 3.94; 95% CI, 1.13–13.77) were associated with impairment in the adjusted model; no statistically significant association was detected for age. Conclusions: Fracture burden and morphology were associated with permanent functional impairment; an age association was not detected in this relatively small, age-concentrated cohort. Standardized reporting of fracture number, displacement, and intra-articular extension may support long-term follow-up and medicolegal evaluation.

Diagnostics doi: 10.3390/diagnostics16203398

Authors: Adrian Okoń Ingrid C. Landfald Michał Podgórski Roman Frach George Triantafyllou Łukasz Olewnik

Background: A simple MRI-based framework for describing part-specific dominance patterns in the human masseter muscle is lacking. This study aimed to characterize its MRI-visible parts and develop a preliminary part-dominance classification. Methods: This retrospective cross-sectional study analysed 58 clinical MRI examinations, comprising 116 masseter muscles with complete bilateral visualization. The three MRI-visible parts were identified on T2-weighted 3D coronal source images. Thickness and length were measured using a predefined study procedure, and each muscle was assigned a part-dominance type according to which part was thickest. Results: Three distinct parts were identified in all 116 muscles. The inferior part was thickest in 81 muscles (69.8%), the coronoid part in 31 (26.7%), and the middle part in 4 (3.4%). The inferior part was also the longest segment. Conclusions: In this dataset, the human masseter muscle showed a three-part MRI morphology. The findings provide a basis for a preliminary part-dominance classification for anatomical and radiological description. Functional, biomechanical, and clinical correlations require prospective validation.

Diagnostics doi: 10.3390/diagnostics16203397

Authors: Tiziana Biagioli Luisa Lanzilao Francesca Romano Sara Ciullini Mannurita Valentina Becherucci Enza Aiello Alessandra Fanelli Alessandra Celli Anna Maria Grazia Gelli Edda Russo

Serum protein electrophoresis (SPE) remains a central laboratory method for the detection and characterization of monoclonal gammopathies and other dysproteinemic patterns. Despite substantial analytical automation, interpretation still relies largely on graphical representation and expert visual assessment, making low-amplitude or borderline abnormalities particularly challenging. Artificial intelligence (AI), including machine-learning (ML) and deep-learning (DL) approaches, has increasingly been applied to SPE, with high performance reported for automated recognition of established abnormalities, particularly M-proteins, i.e., monoclonal immunoglobulins or immunoglobulin fragments produced by clonal plasma cells. However, most models have been developed against predefined diagnostic targets and evaluated using expert interpretation, immunofixation, or immunotyping as reference standards. Improved recognition of known abnormalities should therefore not be equated with discovery of additional clinically meaningful information. Modern electrophoretic platforms generate machine-readable numerical signals that may preserve features not explicitly considered during routine graphical interpretation. This creates the possibility of extending AI-assisted SPE from conventional pattern recognition toward detection of low-amplitude, distributed, or sub-visual signal characteristics. Yet current literature has focused predominantly on algorithmic performance, while the validation pathway required to determine whether additional AI-detected features are biologically meaningful and clinically actionable remains insufficiently defined. Evidence is strongest for automated M-protein recognition, including low-amplitude abnormalities, whereas non-canonical systemic patterns, longitudinal signal analysis, and AI-assisted decomposition of therapeutic monoclonal antibody interference remain exploratory. This critical review addresses this translational gap by evaluating AI applications according to the nature of detected information, strength of supporting evidence, and proximity to clinical implementation. We propose a translational framework addressing four complementary domains: analytical validity, biological validity, clinical validity, and clinical utility. The evidence required in each domain depends on the intended claim and clinical use.

Diagnostics doi: 10.3390/diagnostics16203396

Authors: Emma Verelst Sam Bayat Sylvia Verbanck Gert Van Gompel Johan de Mey Nico Buls

Background/Objectives: Pulmonary diseases exhibit spatially heterogeneous functional and structural abnormalities that are inadequately represented by conventional lung function testing. This pilot study investigates dynamic xenon-enhanced dual-energy CT (Xe-DECT) for a multiparametric assessment of lung ventilation and tissue. Methods: Four mechanically ventilated rabbits were scanned during washout of 70% xenon in oxygen using multibreath imaging with a clinical DECT both before (baseline) and after methacholine administration (post-MCh). Tracheal Xe concentration (CXe) and flow were monitored using mass spectrometry and pneumotachometry to estimate specific ventilation (sV˙ms) and end-expiratory lung volume (EELVms). DECT-derived xenon concentration and tissue density images (mg/mL) were obtained by material decomposition, yielding sV˙DECT and EELVDECT, respectively. Agreement with mass spectrometry and differences between baseline and post-MCh were assessed. Results: The baseline sV˙DECT and EELVDECT agreed with the mass spectrometry, with mean differences of 0.6 min−1 [−0.2 min−1, 1.4 min−1] and 0.6 mL [−6.7 mL, 7.9 mL], respectively. Following MCh administration, the mean differences increased to −2.9 min−1 [−4.1 min−1, −1.6 min−1] for sV˙ and 1.3 mL [−15.3 mL, 12.8 mL] for EELV. Post-MCh, sV˙DECT decreased from 8.6 ± 1.6 min−1 to 3.7 ± 0.9 min−1 (p = 0.034) and EELVDECT from 29.3 ± 1.0 mL to 27.0 ± 1.3 mL (p = 0.036), whereas sV˙ms (p = 0.308) and EELVms (p = 0.653) showed no substantial changes. Regional analysis revealed that sV˙DECT in well-ventilated regions matched tracheal sV˙ms. Conclusions: Dynamic Xe-DECT imaging enabled spatial and quantitative assessments of specific ventilation and tissue densities in an in vivo rabbit model. This technique allowed detection of focal alterations that remained undetected by tracheal measurements.

Diagnostics doi: 10.3390/diagnostics16203395

Authors: Sinem Atay Görür Merve Önder Özer Çelik İbrahim Şevki Bayrakdar Sérgio Lúcio Pereira de Castro Lopes Andre Luiz Ferreira Costa Kaan Orhan

Background/Objectives: This study evaluated the feasibility of a YOLOv5-based model for automated segmentation of these structures and automated measurement of mandibular cortical width (MCW) and panoramic mandibular index PMI. Methods: Five hundred panoramic radiographs were retrospectively collected. The mandibular cortex and the right and left mental foramina were annotated with polygon labels as three separate classes and verified by an experienced radiologist; intra- and inter-observer reliability was evaluated on a random 10% subset. A YOLOv5s-seg model was trained for 500 epochs and evaluated on an independent, patient-level test set. Model performance was quantified with precision, recall, F1 score, Dice coefficient, mean intersection over union (mIoU), and mean average precision (mAP@0.5 and mAP@0.5:0.95). Results: The model achieved a precision of 0.94, a recall of 0.82, and an F1 score of 0.88 (mAP@0.5 = 0.86; mAP@0.5:0.95 = 0.52). The Dice coefficient was 0.93 for the mandibular cortex and 0.80 and 0.75 for the right and left mental foramina, respectively. In the side-level paired agreement analysis (62 measurable sides from 44 test-set patients), the ICC was 0.89 (95% CI: 0.84–0.93) for MCW, with a mean bias of +0.08 mm and 0.87 for PMI, with a mean bias of +0.01. Conclusions: YOLOv5 showed high agreement with expert observers for mandibular cortex segmentation and moderate agreement for the mental foramen, supporting the technical feasibility of automated MCW and PMI measurement. Because missed mental foramen detections reduce the number of measurable sites, automated measurement should be combined with a verification step.

Diagnostics doi: 10.3390/diagnostics16203394

Authors: Saime Sundus Uygun Nihal Comez Osman Selcuk Duysak Evrim Kilicli Murat Konak Hanifi Soylu

Background/Objectives: The decision to administer surfactant therapy to preterm newborns is typically based on clinical respiratory findings, oxygen requirements, and the level of respiratory support. The aim of this study was to assess the association of admission complete blood count parameters and derived systemic inflammatory indices with surfactant administration within the first 24 h of life in preterm infants born at ≤32 weeks of gestation, and to evaluate their discriminative performance. Methods: This single-center, retrospective observational cohort study included 100 preterm infants with a gestational age of ≤32 weeks who were admitted to the neonatal intensive care unit between 1 January 2025 and 31 March 2026. The results of the initial complete blood count and blood gas analysis, obtained as part of routine clinical care at admission, were recorded. Systemic inflammatory indices, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), red cell distribution width-to-platelet ratio (RPR), systemic immune-inflammation index (SII), and mean platelet volume-to-platelet ratio (MPV/PLT), were calculated from the complete blood count results. The primary outcome was surfactant administration within the first 24 h of life. Associated factors were evaluated using logistic regression analysis, and the discriminative performance of continuous variables was assessed using receiver operating characteristic (ROC) curve analysis. Results: Surfactant was administered to 45 infants (45%) within the first 24 h of life. Infants who received surfactant had lower gestational ages, birth weights, 1- and 5 min Apgar scores, partial pressure of carbon dioxide (PCO2), hemoglobin levels, and hematocrit values. No significant differences were observed between groups in NLR, PLR, MLR, RPR, SII, or MPV/PLT. In multivariable analysis, lower gestational age (OR = 0.65; 95% CI: 0.50–0.84; p = 0.001), small-for-gestational-age (SGA) status (OR = 4.61; 95% CI: 1.25–16.91; p = 0.021), and lower 1 min Apgar score (OR = 0.67; 95% CI: 0.46–0.96; p = 0.031) were independently associated with early surfactant administration. Hemoglobin was not independently associated with early surfactant administration after adjustment. In the ROC analysis, the AUC values were 0.804 for birth weight, 0.776 for gestational age, 0.694 for hemoglobin, 0.677 for hematocrit, and 0.640 for PCO2. Conclusions: Lower gestational age, SGA status, and lower 1 min Apgar score were independently associated with early surfactant administration. No significant associations were observed between the evaluated complete blood count-derived inflammatory indices and early surfactant administration. Although hemoglobin and hematocrit levels differed between groups, hemoglobin was not independently associated with the outcome after adjustment. ROC analysis provided descriptive estimates of the discriminative performance of gestational age, birth weight, hemoglobin, hematocrit, and PCO2.

Diagnostics doi: 10.3390/diagnostics16203393

Authors: Andres Calva Lopez Daniel Sanchez Zalabardo Sara Esparza Alamanzon Maria Rodriguez Gomez Carlos Andres Yanez Ruiz Vanessa Talavera Cobo Lucia Polanco Pujol Francisco Javier Ancizu Marckert Luis Labairu Huerta Fernando Jose Diez-Caballero Alonso Fernando Ramon de Fata Chillon Bernardino Miñana Lopez

Background/Objectives: Hypothermic machine perfusion (HMP) has established itself as an evidence-based and effective preservation strategy to improve graft function and survival after kidney transplantation. It demonstrated a reduction in the incidence of delayed graft function (DGF) compared to static cold storage. However, the risk factors for DGF that persist when HMP is used universally are poorly defined. The aim of this study was to explore donor and recipient factors associated with DGF in a universal HMP kidney transplantation program. Methods: A single-center retrospective cohort included 134 consecutive deceased-donor kidney transplants (KTs). The primary endpoint was the incidence of DGF. Secondary endpoints included functional results, complications and survival during follow-up. Univariable and multivariable logistic regression models were performed to identify factors associated with DGF. Graft and patient survival were estimated by the Kaplan–Meier method. Graft function was assessed by serum creatinine (Cr) and estimated glomerular filtration rate (eGFR). Results: The overall incidence of DGF was 9.7% (n = 13). When stratified by donor type, the incidence of DGF was 13.3% (n = 10) for donors after brain death (DBD) and 5.1% (n = 3) for donors after circulatory death (DCD). DGF was associated with impaired graft function during follow-up, a longer in-hospital stay and a higher incidence of major complications. Donor diabetes mellitus (DM) (adjusted OR 4.09, 95% CI 1.14–14.62; p = 0.030) and lower recipient pre-KT hemoglobin (Hb) (adjusted OR 0.62 per 1 g/dL, 95% CI 0.41–0.93; p = 0.021) were associated with DGF; Firth penalized estimates were consistent, but the association with donor DM was attenuated after adjustment for donor age and CIT (OR 3.38, 95% CI 0.91–12.00). Overall graft and patient survival were 99.3% and 100%, respectively, at 12 months, and 99.3% and 96.9%, respectively, at 36 months. Conclusions: Lower recipient pre-KT Hb was consistently associated with DGF in this exploratory cohort, whereas the association with donor DM was attenuated after adjustment for donor age and CIT. Within this universal HMP program, DGF incidence did not differ significantly between DBD and DCD grafts; however, in the absence of an SCS comparator, this observation cannot be attributed to HMP. Given the limited number of events (n = 13), the lack of detailed donor DM information and the absence of PRA data, these findings are hypothesis-generating and require validation in larger prospective studies.

Diagnostics doi: 10.3390/diagnostics16203392

Authors: Pınar Karabak Bilal Hatice Şahin Fatma Özkan Sipahioğlu Gül Meral Kocabeyoğlu Aşır Eren Seven Mustafa Kemal Bayar

Background/Objectives: Adult modified Renal Angina Index (mRAI) formulations predict acute kidney injury, but their association with major adverse kidney events at 90 days (MAKE90) remains unclear. We examined the association in critically ill adults without established chronic kidney disease (CKD). Methods: This retrospective cohort included 250 adults admitted to a tertiary intensive care unit (ICU) between December 2023 and April 2025. mRAI was calculated from data available at ICU admission. MAKE90 was defined as death, renal replacement therapy, or persistent renal dysfunction within 90 days. We used logistic regression, receiver operating characteristic analysis, and nested-model comparisons. Results: Admission mRAI was higher in patients with MAKE90 than in those without MAKE90 (median 10 [IQR 5–20] vs. 3 [IQR 1–6]; p < 0.001). After adjustment for SOFA score and sepsis, mRAI remained associated with MAKE90 (adjusted OR per point from the linear model, 1.073; 95% CI, 1.032–1.116). Spline analysis demonstrated a significant nonlinear association (p = 0.004), indicating that the per-point OR should be interpreted as a summary estimate rather than a constant effect across the score range. The AUC of mRAI was 0.752 (95% CI, 0.691–0.814), higher than that of admission AKI stage (0.653) and not significantly different from APACHE II (0.702) or SOFA (0.718). Adding mRAI to SOFA and sepsis raised the AUC from 0.735 to 0.782. Conclusions: In critically ill adults without established CKD, higher admission mRAI remained associated with MAKE90 after adjustment for SOFA score and sepsis and showed moderate discrimination. External validation in larger, independent cohorts is needed to confirm these findings.

Diagnostics doi: 10.3390/diagnostics16203391

Authors: Aykut Kaşkaya Baha Şen

Background/Objectives: When a box-prompted segmentation pipeline loses accuracy on new data, the detector proposing the box or a later stage may be responsible; this study measured which. Methods: A real-time detection transformer (RT-DETR) feeding the Segment Anything Model 2.1 was compared with a detector-free model (MedSAM3 with a low-rank adapter) on whole-tumor Dice in 158 patients with glioma: held-out Brain Tumor Segmentation (BraTS) 2020 cases (n = 24), the RHUH-GBM glioblastoma cohort (n = 39), and BraTS-Africa (n = 95, glioma presumed). Giving the segmenter the ground-truth box splits the Dice gap between the systems into a detector-stage term and a residual. Results: The detector-stage term was +0.006 Dice on held-out cases, +0.018 on RHUH-GBM, and +0.091 on BraTS-Africa. Its increase over the held-out value was +0.0854 [95% CI +0.0450, +0.1303] on BraTS-Africa (Holm-adjusted p < 0.001) and, after correction of a preprocessing fault, +0.0120 [−0.0062, +0.0295] on RHUH-GBM, which was not resolved. On BraTS-Africa, it came mainly from slices without a detector box. No residual change was resolved. Conclusions: On BraTS-Africa, the detector stage accounted for most of the increase in the pipeline’s gap; on RHUH-GBM, no increase was resolved. The decomposition should be measured per cohort.

Diagnostics doi: 10.3390/diagnostics16203390

Authors: Emrah Zayman Feyza İnceoğlu

Background/Objectives: From a histological and embryological perspective, sperm identification and morphological classification are distinct assessment tasks. This study compares image-level error distributions and review-referral outcomes between separately trained conditional components and direct three-class learning. Methods: Following duplicate-image and label audits, 2947 images from the Sperm Morphology Image Dataset (SMIDS) were analyzed without changing the source labels. Logistic regression models using frozen EfficientNet-B0 features were evaluated using five outer and three inner cross-validation folds that preserved 2942 similarity groups. Final class probabilities, component probabilities, and outcomes at matched review volumes were compared. Results: Overall accuracy was 83.98% for the two-stage model and 84.80% for the direct model. Misclassification of non-sperm images as sperm decreased from 94 (direct) to 77 (two stage), whereas misclassification of true sperm images as non-sperm increased from 82 to 141. When each model referred 973 images for review, accuracy among the remaining 1974 images was 93.67% and 94.48%, respectively. Conclusions: The two models differed in the trade-off between erroneously including non-sperm material and excluding assessable sperm images. Overall and selective accuracy were higher for the direct model. The study provides a framework for jointly evaluating these two error directions on the same test images and at matched review volumes in preliminary histomorphological assessment.

Diagnostics doi: 10.3390/diagnostics16203389

Authors: Yong-Jin Park Moon-Il Park

Cervical insufficiency is conventionally classified by indication and named operative technique, yet neither fully describes the cervix as a dynamically remodeling, mechanically loaded, and structurally heterogeneous organ or specifies the reconstruction delivered. This Perspective proposes precision cervical reconstruction, a conceptual state-informed framework linking five domains: dynamic cervical phenotype, state-based operative assessment, mechanical objective, intended configuration, and achieved reconstruction. Safety and biological eligibility constrain the entire pathway. In the ultrasound-indicated context, morphology and trajectory complement cervical length, whereas elastography and other biomechanical measurements remain research-oriented. In emergency states, bulging extent, membrane reducibility, and cervical rim adequacy separately describe procedural complexity and feasibility. The framework distinguishes clinical observation, plausible mechanical interpretation, and testable hypothesis; it does not replace established indications or constitute a validated treatment-selection algorithm. Suture height, axial separation, sequence, material, tissue engagement, and membrane relationship are treated as reportable variables, and double-level cerclage is considered one conditional configuration rather than a universally superior strategy. Current comparative evidence does not establish consistent benefit from an additional suture or identify a validated state in which vertically distributed support improves outcomes. The immediate contribution is a standardized reasoning and reporting structure that separates indication from state, intended configuration from achieved reconstruction, and mechanistic hypotheses from clinical effectiveness. Prospective studies should establish measurement reliability, procedural fidelity, safety, and associations with maternal and neonatal outcomes before testing state-guided care.

Diagnostics doi: 10.3390/diagnostics16203388

Authors: Mohammed Ageeli Hakami

In tamoxifen-related endometrial alterations, a challenge arises due to the similarity between clinically significant diseases and both benign proliferation and benign polyps. This narrative review examines the clinical assessment, imaging, tissue sampling, biomarkers, and prediction models for women taking tamoxifen. We searched PubMed/MEDLINE and selected articles from reference lists up to August 2026, focusing on human studies reporting diagnostic performance, biomarkers, sampling limitations, or clinical prediction. Evidence was divided into three groups: tamoxifen-specific clinical studies, external studies of endometrial cancer, and mechanistic investigations; however, the heterogeneous populations and endpoints prevented pooled accuracy estimates. Although thickening of the endometrium is associated with an increased risk of abnormal bleeding, the finding when there is no abnormal bleeding is not significant enough to warrant routine surveillance of asymptomatic users. Representative histopathology remains the key, especially if hysteroscopy is used for sampling, particularly if the area is focal or if a diagnosis is not reached. These tissue markers primarily reflect the biology of exposure and show promise in methylation, cytology, serum-marker, and prediction studies, mostly in populations that are not tamoxifen-validated. Thus, reported discrimination does not provide sufficient reassurance to exclude atypical hyperplasia or carcinoma in tamoxifen users. The priorities are prospective validation in well-defined symptomatic patient groups, independent validation of locked assays or models against clinical baseline, and a focus on missed significant disease, avoided procedures, and patient outcomes. The current evidence favors a cautious diagnostic evaluation and does not define a biomarker-based screening or surveillance approach for women taking tamoxifen.

Diagnostics doi: 10.3390/diagnostics16203387

Authors: Yuki Katoh Yosuke Fujii Nagi Yamazaki Akiko Kubo Saki Kamata Yuki Okuma Ting Yang Ayase Futatsugi Masaki Sakamoto Hirotsugu Hino Tadashi Ogawa Mamiko Fukuta Takashi Iwata Hiroshi Nishio Masaki Sugawara Kei Kawana Shuichi Hirai

Background/Objectives: Cervical cancer (CC) is usually caused by high-risk human papillomavirus (hrHPV); however, some hrHPV-negative cases are undetectable by current screening programs. We evaluated a previously established diagnostic model based on serum free fatty acids (FFAs) in an independent cohort including hrHPV-negative CC. Methods: We analyzed serum FFAs from 101 patients with CC (16 hrHPV-negative), 60 healthy donors, and 16 patients with benign gynecological diseases, none of whom were included in the previous study, and gene expression levels of fatty acid metabolism-related enzymes in 64 surgical CC and five normal cervix samples. Results: Levels of nine FFAs differed between CC and the non-cancer groups but not between hrHPV-negative and hrHPV-positive CC. Gene expression levels of acetyl-CoA carboxylase 1, fatty acid synthase, stearoyl-CoA desaturase 1, and monoacylglycerol lipase were increased in CC compared with normal tissues, with no significant differences between hrHPV-negative and hrHPV-positive CC. The previous model (diagnostic index = −5.631 + 0.030 × (stearic acid) + 9.188 × (dihomo-γ-linolenic acid)) distinguished CC from the non-cancer groups (area under the curve, 0.969). At the pre-specified cut-off value, sensitivity was 97.0% (hrHPV-negative CC, 93.8%) and specificity in healthy donors was 58.3%; at the cut-off value derived in this cohort, these were 82.2% (93.8%) and 98.3%, respectively. In hrHPV-negative CC, the positivity rate exceeded those of squamous cell carcinoma antigen, carcinoembryonic antigen, and CA125. Conclusions: The serum-FFA-based diagnostic model detected CC, including hrHPV-negative cases, in an independent cohort. With calibration of the cut-off value, this approach may complement existing HPV-based testing.

Diagnostics doi: 10.3390/diagnostics16203386

Authors: Alina Anton Dan Brebu Meda-Ada Bugi Andreea-Adriana Neamțu Anca-Maria Căpraru Nicoleta Zurbău-Anghel Dana Iovănescu Teodor-Andrei Maghiar Paul Pașca Flaviu-Ionuț Faur Sorin Dan Chiriac Dan Iliescu Bogdan Dan Totolici Octavian Crețu Cristina-Adriana Dehelean Carmen Neamțu

Background/Objectives: Organised colorectal cancer screening is still being introduced in Romania, and the yield of opportunistic colonoscopy outside it is poorly documented. Our primary aim was to describe the histopathological spectrum and the yield of advanced neoplasia in an opportunistic colonoscopy service; a secondary, exploratory aim was to describe self-reported lifestyle items in a questionnaire subgroup. Methods: This study represents a retrospective cross-sectional analysis of consecutive colonoscopies (June 2023–June 2024) at a county hospital outside organised screening, restricted to patients from whom material reached histopathology; the comparison group therefore comprises patients whose sampled lesions were benign, not patients without neoplasia. Advanced neoplasia was defined histologically as adenocarcinoma or adenoma with high-grade dysplasia, without the 10 mm size criterion. A convenience subgroup self-completed a locally developed, unvalidated questionnaire before the procedure; its items were tested against advanced neoplasia and adenocarcinoma with false discovery rate correction. Results: Among 274 patients, 45 (16.4%) had adenocarcinoma, 139 (50.7%) adenoma and 72 (26.3%) advanced neoplasia; per examination (n = 978), detection was 4.6% for adenocarcinoma and 7.4% for advanced neoplasia. Forty-four of 45 carcinomas were graded as moderately differentiated, and no serrated lesion was separately reported. Age was associated with advanced neoplasia (OR 1.34 per decade, 95% CI 1.01–1.79). Questionnaire data were available for only 79 patients (28.8%), among whom adenocarcinoma was more frequent than among non-respondents (26.6% vs. 12.3%). In this subgroup, obesity was inversely (OR 0.07, 95% CI 0.02–0.28) and reported weight loss positively (OR 6.77, 2.26–20.30) associated with advanced neoplasia, and two coffee items were inversely associated; processed meat, dairy, aspirin and supplement use were not associated after correction. Conclusions: Opportunistic colonoscopy at this centre recovered a high proportion of carcinoma, consistent with symptom-driven presentation, and the reporting of serrated lesions and tumour grade requires standardisation. The questionnaire findings rest on a small, selected subgroup and are hypothesis-generating only. The inverse obesity association is most plausibly explained by selection of the comparison group and of respondents, and none of the associations identifies a risk factor.

Diagnostics doi: 10.3390/diagnostics16203385

Authors: Elçin Özdemir Tutar Pınar Öztürk

Background/Objectives: Multiple sclerosis (MS) has been associated with subclinical cardiovascular involvement, including impaired myocardial deformation and increased arterial stiffness. However, the local elastic properties of the ascending aorta and their relationship with subclinical left ventricular (LV) longitudinal dysfunction remain insufficiently characterized in MS. Methods: In this prospective cross-sectional study, 67 adults with MS and 67 age-matched controls without cardiovascular disease underwent standardized transthoracic echocardiography. Aortic strain, distensibility and stiffness index (β) were derived from M-mode ascending aortic diameters and simultaneous brachial blood pressure, and LV global longitudinal strain (GLS) was measured by two-dimensional speckle-tracking echocardiography. Multivariable linear regression was utilized to assess associations. Results: LV ejection fraction was similar between groups, while LV GLS was less negative in MS (−17.49 ± 1.81% vs. −19.85 ± 1.80%, p < 0.001). Patients with MS had lower aortic strain (7.54 ± 3.66% vs. 12.91 ± 3.84%) and distensibility (3.81 [2.23–6.06] vs. 5.95 [4.90–9.26] × 10−3 mmHg−1) and a higher stiffness index (4.77 [3.10–7.10] vs. 3.44 [2.31–4.05]) (all p < 0.001). After adjustment for age, sex, and body mass index, MS remained independently associated with aortic strain, distensibility, and stiffness index. Within the MS group, aortic strain was independently associated with LV GLS after adjustment for age, sex, body mass index, Expanded Disability Status Scale score and LDL cholesterol (B = −0.276, standardized β = −0.558, p < 0.001). LV GLS was independently associated with log-transformed distensibility (B = −1.021, p = 0.011) and stiffness index (B = 1.095, p = 0.014). Conclusions: Patients with MS show concurrent, inter-related impairment of local ascending aortic elasticity and LV longitudinal deformation despite preserved ejection fraction. Further studies are needed to establish the temporal sequence and prognostic relevance of these findings.

Diagnostics doi: 10.3390/diagnostics16203384

Authors: Ahmed Najjar Zeyad Al-Shaibani Nusaibah Basahel Obai M. Raffah Yasir Hassan Elhassan

Background and Clinical Significance: Rosai–Dorfman disease (RDD) is a rare non-Langerhans-cell histiocytosis that infrequently involves the central nervous system. Intracranial RDD commonly presents as a dural-based enhancing mass that radiologically resembles a meningioma. Posterior fossa involvement is particularly uncommon and may cause cerebellar compression and obstructive hydrocephalus. Case Presentation: A 58-year-old man with biopsy-confirmed systemic extranodal RDD presented with progressive headache, nausea, severe dizziness, gait instability, cerebellar ataxia, and right upper-limb dysmetria despite corticosteroid therapy. Brain magnetic resonance imaging demonstrated a strongly enhancing right posterior fossa dural-based mass with vasogenic edema, cerebellar compression, fourth-ventricular effacement, and mild obstructive hydrocephalus. A smaller anterior dural-based enhancing lesion was also identified. The radiological differential diagnosis included meningioma, metastatic disease, and an inflammatory lesion. Following multidisciplinary perioperative management of anemia and complex transfusion incompatibility, gross-total resection of the symptomatic posterior fossa lesion was achieved. Histopathological examination demonstrated histiocytic proliferation with emperipolesis. The lesional histiocytes expressed S100 and CD68, showed nuclear Cyclin D1 expression in approximately 30% of lesional histiocytes, and were negative for CD1a, supporting the diagnosis of intracranial extranodal RDD. Postoperatively, the patient’s headache and cerebellar manifestations improved. Follow-up imaging demonstrated complete resection of the posterior fossa lesion, resolution of the mass effect and hydrocephalus, and no recurrence at the resection site. Extracranial disease subsequently progressed, emphasizing the distinction between local and systemic disease control. Conclusions: Intracranial RDD should be considered in the differential diagnosis of meningioma-like posterior fossa masses, particularly in patients with systemic RDD. Histopathological and immunohistochemical confirmation is essential. Timely surgical resection can provide a definitive diagnosis, effective decompression, and sustained neurological improvement, while continued systemic surveillance remains necessary.

Diagnostics doi: 10.3390/diagnostics16203383

Authors: Vladimir O. Sigin Tamara A. Savina Nikolay N. Chekanov Sergey N. Avdeev Natalya V. Trushenko Olga A. Suvorova Baina B. Lavginova Iuliia A. Levina Olesya V. Kuryleva Goulnara Yu. Babadjanova Viktor M. Misharin

Background/Objectives: The MUC5B rs35705950 polymorphism is the strongest common genetic risk factor for idiopathic pulmonary fibrosis (IPF), whereas its role in fibrotic hypersensitivity pneumonitis (fHP) remains incompletely characterized, particularly in Eastern European cohorts. This study aimed to evaluate the distribution of MUC5B rs35705950 genotypes and alleles in Russian patients with IPF and fHP and to assess their association with disease susceptibility using a large external Russian reference dataset. Methods: The study included 114 patients with interstitial lung disease: 50 with IPF and 64 with fHP. Genotyping was performed using a custom PCR-restriction fragment length polymorphism assay. Genotype and allele frequencies were compared with an external reference dataset from the National Genetic Initiative of Russia (n = 89,261). Association analyses were performed under dominant T-carrier and allelic models. Results: The rs35705950 T allele was significantly enriched in both IPF and fHP compared with the external reference dataset. T-carrier genotypes were detected in 52.0% of patients with IPF and 42.2% of patients with fHP, compared with 18.9% in the reference dataset. T-allele frequencies were 28.0%, 26.6%, and 10.0%, respectively. In the dominant model, T-carrier status was associated with increased odds of IPF (OR = 4.65; 95% CI, 2.56–8.46; p < 0.001) and fHP (OR = 3.13; 95% CI, 1.83–5.29; p < 0.001). The direct comparison between IPF and fHP was inconclusive because of limited statistical power. Conclusions: In this Russian clinical cohort, the rs35705950 T allele was more frequent in patients with IPF and fHP than in the external Russian reference dataset. These findings provide regional replication of previously reported associations. The study did not assess causal mechanisms or diagnostic performance.

Diagnostics doi: 10.3390/diagnostics16203382

Authors: Yuxiang Feng Chaofeng Liang Shujun Wang

Background/Objectives: Forecasting the individual anatomical response to anti-vascular endothelial growth factor (anti-VEGF) therapy from optical coherence tomography (OCT) could support the management of diabetic retinal disease. Direct volumetric generation is difficult because treatment-associated change is local while most of the retina is stationary, so generative models regress to the mean and blur retinal layers. Methods: We propose a two-stage framework that decouples baseline anatomy from longitudinal change in 3D-OCT. A Retinal Response Tokenizer compresses the latent residual between baseline and follow-up volumes into discrete action tokens via Finite Scalar Quantization (FSQ), and a conditional decoder renders the follow-up volume from baseline features and these tokens. An Action Transformer predicts the tokens from the baseline scan, the follow-up interval, and baseline covariates. Results: On the OLIVES trial cohort (diabetic retinopathy and macular edema; 738 test pairs from five held-out eyes), our method achieved the highest structural similarity in every test eye (SSIM 0.657 vs. 0.543–0.623) and tracked the central subfield thickness (CST) change measured by a frozen regressor (Δ-r=0.88). In a five-fold cross-validation over 52 eyes, it improved PSNR over an identity copy by 1.27 dB (95% CI 0.93–1.57) and reduced the CST change error by 10.5 μm (95% CI 3.1–19.4). Conclusions: Prospective validation is required before clinical use.

Diagnostics doi: 10.3390/diagnostics16203379

Authors: Aiganym Amanova Bekbolat Zholdin Saule Balmagambetova Iliada Talipova Gulnara Kurmanalina Saule Madinova Mira Baspayeva Kulparshan Kubenova Gulmira Sultanbekova Maria Poltavskaya Zhenisgul Tlegenova

Background/Objectives: The HFA-ICOS baseline cardiovascular risk classification was developed to standardize pretreatment risk stratification before potentially cardiotoxic cancer therapy, but its external performance across diverse populations remains incompletely characterized. We prospectively evaluated its performance in women with breast cancer receiving anthracycline-containing therapy in Central Asia. Methods: This prospective single-center external validation study used data from the PREDICATE cohort (ISRCTN12628444). Participants were classified at baseline as being at low, moderate, high, or very high cardiovascular risk according to the HFA-ICOS classification before treatment and outcome ascertainment; the high- and very-high-risk categories were pooled for analysis because of small numbers. Participants underwent serial cardiovascular surveillance, including echocardiographic assessment of left ventricular ejection fraction and global longitudinal strain, together with serial cardiac biomarker measurements. The primary outcome was cancer therapy-related cardiac dysfunction (CTRCD), defined according to the 2022 ESC cardio-oncology criteria. Results: The analysis included 108 participants. CTRCD occurred in 43 of 108 participants (39.8%). The observed proportion of participants who developed CTRCD increased from 30.0% in the low-risk group to 47.5% in the moderate-risk group and 75.0% in the high/very-high-risk group (p = 0.026). Kaplan–Meier analysis demonstrated significant separation of CTRCD-free survival across HFA-ICOS risk categories (log-rank χ2 = 10.12; p = 0.006). Compared with the low-risk group, the hazard of CTRCD was higher in the moderate-risk group (hazard ratio [HR], 2.16; 95% confidence interval [CI], 1.13–4.13) and high/very-high-risk group (HR, 3.59; 95% CI, 1.42–9.11). Discrimination was modest (area under the curve, 0.630; 95% CI, 0.530–0.724). Conclusions: The HFA-ICOS classification demonstrated a clear ordinal gradient in CTRCD risk and significant time-to-event separation but showed limited discrimination at the individual-patient level. It may guide initial risk stratification but should be complemented by longitudinal cardiovascular surveillance rather than used as a stand-alone predictor.

Diagnostics doi: 10.3390/diagnostics16203380

Authors: Paul Filip Curcă Mioara Laura Macovei Ovidiu Mușat Mihail Zemba Andreea Alexandra Mihaela Muşat Mihai Adrian Păsărică Silvia Victoria Prodescu Cătălina Ioana Tătaru Călin Petru Tătaru

Background/Objectives: Artificial Intelligence (AI) technology—in the form of Machine Learning (ML) models and other models specialized in image recognition and processing, such as Convolutional Neural Networks Visual Transformers (CNN-ViTs)—is increasingly being used in ophthalmology. This review summarizes the main AI applications for laser-assisted refractive surgery. Methods: A wide-ranging literature search on the PubMed and ISI Thompson Web of Science databases was conducted. Results: AI is an all-encompassing technological concept that refers to either specific applications of ML/CNN models, such as in keratoconus screening or diagnosis, or agentic/multimodal AI applications that process different data types using a variety of AI models. The most clinically established applications found were corneal ectasia and keratoconus screening, in which AI models can reliably exceed 95% diagnostic accuracy, specificity, and sensitivity; nomogram-derived laser ablation programming; optimization of ray-tracing calculations for ray-traced ablation profiles; patient screening and selection for refractive surgery; visual and refractive result prediction; assessment of postoperative corneal ectasia risk; detection of intraoperative complications; research on the laser coupling effect; and other applications such as monitoring eye rubbing behavior in corneal ectasia suspects. Thus, singular, specific applications of AI models have made the largest clinical contributions. These results must be interpreted with a comparison of internal versus external validation, calibration, and generalizability. Overall the technology is highly promising. Agentic/multimodal AI frameworks are currently being discussed, with pilot studies published and applicability proposed in the context of large, high-patient-volume clinical practices. The technological advent of SHAP force plot graphs and saliency maps has improved understanding of the factors that contribute mechanistically to AI model reasoning, leading to more informed clinical decisions or research applicability, such as in finding parameters or factors linked to postoperative ectasia. Conclusions: AI is already established in laser-assisted refractive surgery in the form of models specialized in data-intensive analysis. At present, the best-performing novel AI models originate from the domain of large or multi-hospital settings due to requirements for multiple latest-generation diagnostic devices, high-volume patient data, computing expertise, and resources. Future directions could include clinical standardization and trickle-down dissemination of the technology. Agentic/multimodal AI has the potential to benefit large clinical/patient settings or offer access to expert knowledge in smaller practice settings. Agentic/multimodal AI implementation is offset by challenges in complexity, the technological limitations of LLMs (“hallucinations”), and ethical and legislative factors.

Diagnostics doi: 10.3390/diagnostics16203381

Authors: Levent Deniz Tugay Solar Ipek Deveci Kocakoc Berrin Bercik Inal Okan Dikker Cengiz Aydin

Background/Objectives: This study aimed to develop and evaluate machine learning models for predicting ionized calcium levels in patients with hypoalbuminemia, compare their performance with classical correction formulas and unadjusted total calcium levels, and assess their transportability through external validation. Methods: In a retrospective development cohort of 14,745 adults with hypoalbuminemia, XGBoost and ordinary least squares (OLS) models used total calcium, albumin, total protein, and eGFR and were evaluated with nested cross-validation. Frozen models were then applied without recalibration to an independent external cohort of 2751 patients using the same analyzer platforms. Results: Development XGBoost performance was R2 = 0.500 and AUC-ROC = 0.798 (95% CI 0.788–0.807), with 98.5% sensitivity and 26.0% specificity. External R2 was 0.397 for XGBoost and 0.363 for OLS. External AUC-ROC was 0.818 (95% CI 0.791–0.845) for XGBoost, 0.823 (0.797–0.850) for OLS, and 0.819 (0.791–0.845) for total calcium. Threshold-matched and exploratory decision-curve analyses showed no clear incremental XGBoost advantage over total calcium. Conclusions: Machine learning models provided useful continuous ionized-calcium estimates and high sensitivity for hypocalcemia detection, although specificity was low. In independent external validation, hypocalcemia discrimination was comparable to unadjusted total calcium. The models should be considered complementary rather than substitutes for measured ionized calcium, and further multicenter and prospective evaluation is warranted.

Diagnostics doi: 10.3390/diagnostics16203378

Authors: Easa Alalwany Bader Alsharif

Background/Objectives: Deep learning models for breast tumor segmentation in dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) often lose accuracy at centers that did not contribute training data. We investigated whether case-wise routing between two low-resource adapted models, combined with an uncertainty-based review-prioritization signal, behaves consistently under severe cross-center domain shift. Methods: Using the four public collections of the MAMA-MIA dataset (DUKE, ISPY1, ISPY2, NACT; 1231 cases), we performed four-fold leave-one-center-out experiments in which each held-out center contributed only five labeled cases and a pool of unlabeled scans. We compared source-only transfer, five-shot fine-tuning, and teacher–student self-training with AdaSwitch3D, which routes each case between the two adapted branches using 17 label-free features and produces a heuristic review-prioritization signal. The complete pipeline—data splits, five-shot selection, training, adaptation, router construction, and referral calibration—was repeated with five random seeds, and each seed was evaluated once on 80 untouched test cases (400 seed-specific test observations). Results: Across five independent repetitions, mean Dice was 0.325 ± 0.051 for source-only transfer, 0.353 ± 0.052 for five-shot fine-tuning, 0.372 ± 0.047 for teacher–student adaptation, and 0.377 ± 0.057 for AdaSwitch3D; a validation-selected per-center strategy reached 0.376 ± 0.044. AdaSwitch3D exceeded five-shot fine-tuning in all five seeds and teacher–student adaptation in four, but the difference between AdaSwitch3D and teacher–student adaptation was small (mean +0.005) and varied by seed, while inference required both branches (approximately twice the single-model time). Observed test referral rates ranged from 23.8% to 56.3% against a 20% validation target, and low-Dice (<0.20) failure capture ranged from 21.7% to 71.8%. In the prespecified case-level analysis of seed 42, AdaSwitch3D improved on source-only transfer and five-shot fine-tuning (Holm-adjusted p=0.021 for each), whereas the comparison with teacher–student adaptation did not provide evidence of a difference (Holm-adjusted p=0.508). Conclusions: Absolute segmentation accuracy remained low, the incremental benefit of case-wise routing over teacher–student adaptation was small and seed-dependent, and referral behavior was unstable across repetitions. The principal finding is therefore that cross-center adaptation, case-wise model selection, and heuristic referral remain sensitive under limited target supervision. AdaSwitch3D should be interpreted as an exploratory case study of these challenges rather than as a clinically validated segmentation or referral system.

Diagnostics doi: 10.3390/diagnostics16203377

Authors: Antonio Vizzuso Maria Vittoria Bazzocchi Antonio Spina Pasquale Maria Berrino Roberta Gunelli Emanuela Giampalma Matteo Renzulli

Vesico-vaginal fistula (VVF) is a debilitating complication commonly occurring after gynecologic surgery and frequently associated with significant morbidity and impaired quality of life. Although surgical repair remains the standard treatment, management strategies remain heterogeneous, while conservative approaches often require prolonged urinary diversion with variable success rates. We report a case of persistent post-surgical VVF successfully treated with image-guided embolization using n-butyl cyanoacrylate methylsulfone (NBCA; Glubran 2, GEM; Viareggio, Italy) through a transvesical catheter-based approach after failure of conservative management. This case illustrates the potential role of interventional radiology in the management of selected VVFs, suggesting that image-guided fistula embolization may represent a minimally invasive treatment option when conservative management fails and surgical reintervention is undesirable or can be deferred.

Diagnostics doi: 10.3390/diagnostics16203376

Authors: Philip H. Klecker Joscha Steetskamp Annette Hasenburg Yaman Degirmenci

We present the case of a 47-year-old woman (gravida II, para II; both deliveries by cesarean section) with a rare case of a ligamentary leiomyoma appearing as a mass lateral of the mons pubis. The lesion had first been noticed approximately seven months prior to the first examination at our institution and had shown continuous growth since its initial detection. Apart from occasional mild discomfort, no additional symptoms such as skin changes, discharge, or systemic complaints were reported. Based on the clinical and sonographic findings, no suspicion of malignancy was raised during the preoperative assessment, and elective surgical excision was scheduled for both diagnostic and therapeutic purposes. The described lesion presented intraoperatively as a ligamentary leiomyoma and subsequent histopathological examinations confirmed the diagnosis.

Diagnostics doi: 10.3390/diagnostics16203375

Authors: Felix Bratosin Horia Silviu Branea Elena Hogea

Background/Objectives: Untargeted metagenomic sequencing of microbial cell-free DNA or RNA in plasma or serum offers pathogen detection without lumbar puncture or biopsy, but its value in suspected central nervous system (CNS) infection is uncertain. We reviewed diagnostic yield, agreement with CNS-site testing, clinical impact, and failure modes. Methods: PubMed/MEDLINE was searched with seven documented strings (inception to 2 September 2026), supplemented by citation and web searching. Eligible reports were primary human studies of untargeted plasma or serum metagenomic sequencing with a separable result in patients with suspected or confirmed infectious CNS syndromes. Selection, extraction, and design-specific risk-of-bias appraisal followed PRISMA 2020 and were performed independently by two authors with disagreements resolved by discussion; the search was restricted to PubMed/MEDLINE and no protocol was registered. Synthesis was narrative because designs and reference standards were incompatible. Results: Of 190 reports assessed, 69 studies were included (18 denominator-based cohorts, 8 small series, 43 case reports; 51 from the United States). Positive CNS-specific clinical impact in commercial assay cohorts ranged from 0 of 24 adult to 5 of 24 pediatric meningoencephalitis tests. Among 51 case-level reports, the plasma or serum result was concordant with CNS-site testing in 28, positive when CNS-site testing was negative in 5, unconfirmed in 12, and negative or missed the pathogen in 6. All five plasma-only detections came from single case reports, which contributed to no yield or agreement denominator; excluding the four abstract-level case reports moved no proportion by more than 1.3 percentage points. RNA viruses, low-burden focal mould disease, and chromosomally integrated HHV-6 were recurrent sources of false-negative or misleading results. Conclusions: Plasma or serum metagenomic sequencing is a useful adjunct in selected difficult CNS infections, particularly disseminated, fungal, amoebic, or fastidious bacterial disease, but it does not replace CNS-site diagnostics.

Diagnostics doi: 10.3390/diagnostics16203374

Authors: Emmanouela Peteinidou Marino Basha Stylianos Daios Vasileios Anastasiou Evdoxia Stavropoulou Christoforos Tsamtzidis Eleftheria Baltagianni Emmanouil Fardoulis Christos Mantzios Matthaios Didagelos Antonios Ziakas Vasileios Kamperidis

Background: Reliable quantification of systemic venous congestion in acute heart failure (HF) has become feasible with the advent of the venous excess ultrasound (VExUS) score, informing therapeutic management. Nevertheless, the determinants of the VExUS score trajectory during hospitalization and the prognostic implications of persistent subclinical congestion at discharge remain poorly defined. Methods: Consecutive patients admitted for acute HF were prospectively enrolled (n = 418, 73.3 ± 11.8 years old, 59.1% male). VExUS scores were assessed at admission and prior to discharge to categorize the patients into three groups: non-congested (persistent score of 0; n = 81), improved (score reduction of ≥1 point; n = 214), and non-improved (persistent congestion without score reduction; n = 123). Baseline clinical data were collected and all the patients had a transthoracic echocardiogram on admission. All patients were followed up post-discharge and the primary endpoint was a composite of all-cause mortality or HF hospitalization. Results: Patients with non-improved VExUS exhibited a higher burden of right-sided remodeling and dysfunction including larger right chambers, lower right ventricle (RV) systolic function indices, higher RV systolic pressures and a higher prevalence of severe tricuspid regurgitation (all p < 0.001). Severe tricuspid regurgitation was the sole independent predictor of VExUS non-improvement (OR 2.86, 95% CI 1.51–5.45, p = 0.001). Non-improved VExUS (HR 1.77; 95% CI 1.17–2.67; p = 0.007), severe tricuspid regurgitation (HR 1.88; 95% CI 1.16–3.02; p = 0.010) and intravenous furosemide dose (HR 1.00; 95% CI 1.00–1.01; p = 0.011) were independent predictors of the composite primary endpoint. Inclusion of non-improved VExUS provided incremental prognostic value over models including clinical, laboratory, and echocardiographic parameters (Δχ2= 9.22; p = 0.007). Conclusions: VExUS non-improvement throughout hospitalization marks patients with worse primary endpoint Severe tricuspid regurgitation emerges as an independent determinant of VExUS non-improvement which is independently associated with poor long-term outcomes.

Diagnostics doi: 10.3390/diagnostics16203369

Authors: Ömer Emin Çınar Yasemin Adalı

Background/Objectives: The COVID-19 pandemic coincided with widespread disruption of cancer care. We examined changes in lung adenocarcinoma presentation and outcomes across the COVID-19 era and whether diagnosis-time information identifies patients at risk of early death. Methods: Adults with microscopically confirmed lung adenocarcinoma diagnosed during 2018–2023 were identified from the Surveillance, Epidemiology, and End Results 17 Registries database and grouped into three diagnostic periods. Logistic regression, time-varying Cox, and Fine-Gray models evaluated stage, metastasis, surgery, delay, and mortality. Four machine-learning algorithms using only diagnosis-time variables were developed (2018–2021; n = 87,281) and temporally validated (2022; n = 22,012). Results: Among 133,306 patients, COVID-19 versus pre-COVID-19 differences were significant but small in absolute terms: stage IV disease 47.9% versus 47.4% (adjusted odds ratio [OR], 1.03; 95% CI, 1.00–1.06), organ-specific metastasis 45.8% versus 44.4% (OR, 1.06; 1.04–1.09), and treatment delay exceeding 90 days 11.1% versus 10.2% (OR, 1.11; 1.06–1.17). Post-COVID-19 (2022–2023) diagnosis showed less advanced disease but substantially longer delay (14.5% versus 10.2%; OR, 1.45; 1.39–1.52). Gradient boosting achieved a 2022 ROC AUC of 0.840 (0.834–0.845); it flagged 46.8% of patients and correctly flagged 81.6% of those who died, against 44.0% and 75.4% for stage IV classification. Conclusions: COVID-era changes in stage and metastatic presentation were small in absolute terms, whereas the increase in treatment delay was larger and persisted. A diagnosis-time model modestly improved identification of early death beyond stage alone, flagging 28 more patients per 1000, of whom 21 died within the year. These findings support further evaluation; external validation is required before clinical use.

Diagnostics doi: 10.3390/diagnostics16203373

Authors: Freideriki Eleni Kourti Alexios S. Antonopoulos Vasileios Kytinos Theodoros Tsampras Alexandrina Kouroutzoglou Dimitrios Kyriakopoulos Maria Eleni Koilakou Pinelopi Karampina Vasiliki Gardikioti Dimitrios Terentes-Printzios Alexandros Kasiakogias Ioannis Leontsinis Christina Chrysohoou Maria Koutelou Konstantinos Toutouzas Konstantinos Tsioufis Charalambos Vlachopoulos

Background: Diagnoses of transthyretin amyloid cardiomyopathy (ATTR-CM) have increased in recent years, with a growing proportion of patients being identified at earlier disease stages. However, temporal trends in ATTR-CM diagnosis and survival during the tafamidis era in the Greek population remain largely unknown. Methods: This retrospective study included 75 patients with ATTR-CM treated with tafamidis. Baseline demographic, clinical, laboratory, and echocardiographic characteristics were assessed, and survival outcomes were subsequently evaluated. Results: Among 75 tafamidis-treated patients, 14 deaths (19%) occurred during a median follow-up of 20 months [IQR 10.0–30.5] with an estimated 30-month survival of 75%. Kaplan–Meier analysis demonstrated significantly poorer survival among patients aged ≥80 years (log-rank p = 0.013), those with NYHA class III–IV (log-rank p = 0.018), and across progressively more advanced NAC stages I–III (global log-rank p < 0.001). In contrast, survival did not differ significantly according to LVEF <50% versus ≥50% (log-rank p = 0.863) or maximal wall thickness ≥15 mm versus <15 mm (log-rank p = 0.801). After Holm correction across five comparisons, only NAC stage remained statistically significant (adjusted p < 0.001). Conclusions: In this real-world Greek cohort of patients with ATTR-CM treated with tafamidis, the estimated 30-month all-cause mortality was 25% and more advanced NAC stage was associated with poorer survival.

Diagnostics doi: 10.3390/diagnostics16203372

Authors: Amir Zemmouri Marcus Talke Marie Porte Tania Moussa Christophe Massard Gabriel Garcia Remy Barbe Nathalie Lassau Arnaud Dupont Amandine Crombé Douraied Ben Salem Capucine Baldini Tarek Aissi Mabel Nuernberg Corinne Balleyguier Laurent Dercle Samy Ammari

Background: Portal venous phase (PVP) contrast-enhanced CT is a cornerstone for response assessment in early-phase oncology trials, yet contrast-enhancement phase timing remains insufficiently monitored across sites. We assessed PVP timing using a validated artificial intelligence (AI) quality control tool (CECT-QC). Methods: In this retrospective multicenter study, 402 CT examinations from 402 patients enrolled in phase I oncology trials across three European institutions were analyzed using CECT-QC, which quantifies aortic and portal venous enhancement to classify contrast-enhancement phase. The primary analysis included 335 standard CT examinations. Optimal PVP classification was compared (i) across institutions, (ii) before vs. after French regulatory changes impacting contrast delivery, and (iii) across scanner technologies (photon-counting CT [PCCT] vs. standard CT). Results: Among the 335 standard CT examinations included in the primary analysis, 53.1% (178/335) were classified by CECT-QC as optimal PVP. Optimal PVP rates were 39.0% (32/82) at Institution A, 56.9% (87/153) at Institution B, and 59.0% (59/100) at Institution C, with a significant adjusted institutional association (p = 0.039). No significant temporal association was observed before versus after the legislative change (p = 0.716). At Institution A, standard CT was associated with higher odds of optimal PVP classification than PCCT (OR 2.24, 95% CI 1.07–4.68; p = 0.031), while PCCT showed higher aortic and portal venous attenuation (both p < 0.001). Conclusions: Approximately half of standard CT examinations in phase I oncology trials were classified as optimal PVP. Classification varied significantly across institutions and by scanner technology, whereas no significant temporal association was observed before versus after the legislative change. These findings support continued quality-control monitoring, protocol harmonization, and adaptation of classification tools to emerging CT platforms.

Diagnostics doi: 10.3390/diagnostics16203370

Authors: Marta Campillo Ajenjo Beatriz Herrero Ruiz Laura Sotillo Mallo María Carmen Bravo Laguna Olaia Rodríguez Fraga Bárbara Moreno Sanz-Gadea Rebeca Sánchez Salmador Helena Méndez del Sol Roberto Rodríguez González José Luis Bartha Rasero Eugenia Antolín Alvarado

Background: Although cardiac involvement is well characterized in complicated monochorionic (MC) pregnancies, whether subtle cardiovascular changes occur in uncomplicated pregnancies remains unclear. We characterized fetal and neonatal cardiovascular adaptation using echocardiography and cardiac biomarkers. Methods: In this prospective longitudinal cohort, 76 dichorionic (DC) and 68 uncomplicated monochorionic diamniotic (MCDA) twins underwent fetal echocardiography at 28 weeks and neonatal echocardiography within 72 h after birth. Cord blood N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin I (hs-cTnI) and heart-type fatty acid-binding protein (H-FABP) were assessed at delivery. Analyses used generalized estimating equations to account for within-pregnancy clustering and Benjamini–Hochberg correction for multiple comparisons. Associations between cardiac biomarkers and fetal echocardiographic parameters and interactions with chorionicity and gestational age at birth were also evaluated. Results: MCDA fetuses showed trends toward a higher cardiothoracic ratio, lower right ventricular fractional shortening and tricuspid annular plane systolic excursion, and a higher prevalence of tricuspid regurgitation (TR) compared with DC fetuses. In the early neonatal period, nominal differences in interventricular septal thickness and tissue Doppler indices did not persist after FDR correction. Cord-blood hs-cTnI (21.83 vs. 12.29 pg/mL; p = 0.015, FDR-adjusted p = 0.027) and NT-proBNP (1327.6 vs. 887.6 pg/mL; p = 0.018, FDR-adjusted p = 0.027) concentrations were higher in MCDA twins. After gestational age adjustment, the association with hs-cTnI remained relatively stable, whereas that with NT-proBNP was attenuated; neither remained significant after FDR correction (p = 0.116 for both). The TR-hs-cTnI association differed by chorionicity (p for interaction < 0.001, FDR-adjusted p < 0.004) and persisted after adjustment for gestational age at birth. Conclusions: Conventional echocardiographic measures of cardiac structure and function appear to be largely preserved in uncomplicated MCDA twins during fetal life and the early neonatal period. Higher cord-blood hs-cTnI and NT-proBNP may suggest subclinical myocardial stress associated with monochorionicity, although gestational age-adjusted findings warrant caution.