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Keywords = Receiver Operating Characteristics (ROC)

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30 pages, 6311 KB  
Article
Comparative Diagnostic Performance of AFP, PIVKA-II, and the ASAP Score for Hepatocellular Carcinoma: A Large Tertiary Care Referral Center Study from India
by Sowjanya Chamarthi, Pasham Sathwika, Sai V. Sarada, Deepika Gujjarlapudi, Sameer Kumar Akundi, Shantan Venishetty, Manasa Alla, Sowmya Iyengar, Mithun Sharma, Nagaraja Rao Padaki, Nageshwar D. Reddy and Anand V. Kulkarni
Livers 2026, 6(5), 94; https://doi.org/10.3390/livers6050094 - 9 Sep 2026
Abstract
Background: Alpha-fetoprotein (AFP) and protein induced by vitamin K absence-II (PIVKA-Il) are established biomarkers for hepatocellular carcinoma (HCC). The ASAP score, incorporating age, sex, AFP, and PIVKA-II, may improve diagnosis, but data from Indian populations are limited. We compared the diagnostic performance of [...] Read more.
Background: Alpha-fetoprotein (AFP) and protein induced by vitamin K absence-II (PIVKA-Il) are established biomarkers for hepatocellular carcinoma (HCC). The ASAP score, incorporating age, sex, AFP, and PIVKA-II, may improve diagnosis, but data from Indian populations are limited. We compared the diagnostic performance of AFP, PIVKA-II, and ASAP in a large tertiary referral cohort from India. Methods: In this single-center cross-sectional study, consecutive adults with chronic liver disease and healthy controls evaluated at AIG Hospitals, Hyderabad, from January to December 2025 were included. HCC was diagnosed using standard imaging criteria. AFP and PIVKA-II were measured by a chemiluminescent microparticle immunoassay, and ASAP was calculated for each participant. Diagnostic performance was assessed using receiver operating characteristic (ROC) and precision–recall analyses at standard and optimized cut-offs derived from the Youden index and F1-score. Results: Among 1305 participants, 686 were cirrhotic controls, 278 had cirrhotic HCC, 130 were non-cirrhotic controls, and 37 had non-cirrhotic HCC. At standard cut-offs, AFP (20 ng/mL) showed high specificity but low sensitivity, especially for early-stage HCC (93.3% and 29.6%). PIVKA-II (40 mAU/mL) showed high sensitivity but poor specificity (82.7% and 26.4%). ASAP (0.526) provided the best balance, with 69.4% sensitivity and 52.2% specificity in early-stage HCC, 82.0% and 52.2% in cirrhotic HCC, and 81.9% and 55.5% overall. ROC analysis demonstrated superior discrimination for ASAP across cirrhotic, non-cirrhotic, and etiologic subgroups, including metabolic-dysfunction-associated steatotic liver disease (MASLD) HCC. Optimized cut-offs, particularly higher thresholds for PIVKA-II (71.3–98.1 mAU/mL) and ASAP (0.6–0.9), improved the diagnostic balance. Conclusions: The ASAP score modestly outperforms AFP and PIVKA-II, offering better overall diagnostic accuracy for HCC in a MASLD-dominant cohort. Lower cut-offs may improve early detection, but performance in very-early-stage disease remains suboptimal and hence there is limited benefit in surveillance-relevant settings. Higher population-specific cut-offs are required for Indian populations. These findings support the use of these biomarkers as complementary tools alongside imaging for risk stratification rather than standalone screening tests. Full article
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14 pages, 1473 KB  
Article
Evaluation of Serum Soluble Urokinase Plasminogen Activator Receptor (suPAR) Levels in Different Metabolic Obesity Phenotypes and Their Association with Inflammatory Cytokines: A Cross-Sectional Study
by Aycan Acet, Cagla Ozdemir and Hatice Solak
J. Clin. Med. 2026, 15(18), 6990; https://doi.org/10.3390/jcm15186990 - 9 Sep 2026
Abstract
Background: The classification of metabolic risk solely based on body mass index (BMI) fails to acknowledge the heterogeneity inherent in obesity. Soluble urokinase plasminogen activator receptor (suPAR) has been proposed as a stable biomarker of chronic inflammation; however, its behaviour across metabolic obesity [...] Read more.
Background: The classification of metabolic risk solely based on body mass index (BMI) fails to acknowledge the heterogeneity inherent in obesity. Soluble urokinase plasminogen activator receptor (suPAR) has been proposed as a stable biomarker of chronic inflammation; however, its behaviour across metabolic obesity phenotypes defined jointly by adiposity and insulin resistance remains uncertain. Methods: In this cross-sectional study, 190 adults aged 18 to 60 years attending internal medicine outpatient clinics were stratified by BMI (≥30 kg/m2) and homeostasis model assessment of insulin resistance (HOMA-IR ≥ 2.5) into four phenotypes: non-obese insulin-sensitive (NOIS, n = 64), non-obese insulin-resistant (NOIR, n = 50), obese insulin-sensitive (OIS, n = 33), and obese insulin-resistant (OIR, n = 43). Serum suPAR, interleukin-6 (IL-6), and C-X-C motif chemokine ligand 10 (CXCL10) were measured using enzyme-linked immunosorbent assays. Group comparisons, rank-based two-factor analyses, correlation analyses, logistic regression, and receiver operating characteristic (ROC) analyses were performed. Results: Serum suPAR did not differ across the four phenotypes (p = 0.19) and was not correlated with HOMA-IR (ρ = −0.09, p = 0.24). IL-6 was lower in the OIR group than in the NOIS group (p = 0.012). CXCL10 was higher in both obese phenotypes than in both non-obese phenotypes (p < 0.001), and rank-based two-factor analysis attributed this difference to obesity (p < 0.001) rather than insulin resistance (p = 0.71). CXCL10 correlated with BMI (ρ = 0.29, p < 0.001) and remained associated with obesity after adjustment for age, sex, and C-reactive protein (odds ratio per 10 ng/L, 1.12; 95% confidence interval, 1.06 to 1.18). CXCL10 discriminated obesity with an area under the ROC curve of 0.74 (95% CI, 0.66 to 0.81). None of the three biomarkers discriminated insulin resistance (areas under the curve, 0.43 to 0.50). The association between CXCL10 and obesity was consistent in both sexes and unchanged with alternative HOMA-IR cutoffs of 2.0 and 3.0. Conclusions: In this cohort, circulating CXCL10 tracked adiposity rather than insulin resistance, whereas suPAR and IL-6 did not separate metabolic obesity phenotypes. These findings do not support suPAR as a marker of insulin resistance independently of body fat. Full article
(This article belongs to the Section Endocrinology & Metabolism)
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12 pages, 630 KB  
Article
Perioperative Inflammatory Biomarkers and Surgical Site Infection After Pelvic and Acetabular Fracture Surgery: A Retrospective Cohort Study
by Kemal Şibar, Rohat Genç, Mehmet Utku Çiftçi, Mehmet Nur İneci, Hakan Zeybek and Cengiz Yıldırım
J. Clin. Med. 2026, 15(18), 6981; https://doi.org/10.3390/jcm15186981 - 9 Sep 2026
Abstract
Background: Surgical site infection (SSI) remains a serious complication following operative treatment of pelvic and acetabular fractures. Although routinely available inflammatory biomarkers have been investigated for perioperative risk assessment in various orthopedic populations, their association with SSI after pelvic and acetabular fracture [...] Read more.
Background: Surgical site infection (SSI) remains a serious complication following operative treatment of pelvic and acetabular fractures. Although routinely available inflammatory biomarkers have been investigated for perioperative risk assessment in various orthopedic populations, their association with SSI after pelvic and acetabular fracture surgery remains unclear. This study aimed to evaluate the association between perioperative inflammatory biomarkers and postoperative SSI in patients undergoing surgical fixation of pelvic and acetabular fractures. Methods: Adult patients who underwent definitive surgical fixation for pelvic ring and/or acetabular fractures between January 2018 and January 2025 were retrospectively reviewed. Hematological parameters and inflammatory biomarkers, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI), were assessed at admission, preoperatively, and on postoperative day 0. Factors associated with SSI were evaluated using univariable Cox regression and Firth penalized logistic regression, with adjustment for treatment strategy, time to definitive surgery, age, sex, and Injury Severity Score. Exploratory receiver operating characteristic analyses were performed to assess the discriminatory ability of preoperative laboratory parameters and inflammatory biomarkers. Results: Among 104 patients, 12 (11.5%) developed SSI. Univariable Cox regression identified staged treatment (p = 0.015), longer time from injury to definitive surgery (p = 0.023), lower admission platelet count (HR 0.61 per 50 × 109/L increase, 95% CI 0.38–0.97; p = 0.038), and higher admission SIRI (HR 1.03, 95% CI 1.00–1.05; p = 0.048) as factors associated with SSI. In the multivariable Firth-penalized logistic regression analysis, neither staged treatment nor time to definitive surgery remained statistically significant, and none of the included covariates demonstrated a statistically significant independent association with SSI. Exploratory ROC analyses showed limited discriminatory performance of the evaluated preoperative laboratory parameters and inflammatory biomarkers. Conclusions: Routinely available perioperative inflammatory biomarkers demonstrated limited utility for identifying patients at risk of SSI following pelvic and acetabular fracture surgery. The associations of admission SIRI, admission platelet count, staged treatment, and delayed definitive fixation observed in univariable analyses should be considered exploratory. These findings highlight the multifactorial nature of postoperative SSI and warrant validation in larger prospective cohorts. Full article
(This article belongs to the Section Orthopedics)
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14 pages, 1347 KB  
Article
Random Urinary Calcium/Creatinine Ratio as a Predictor of Dehydration in Hypercalcemic and Normocalcemic Patients
by Rotem Tal-Ben Ishay, Yossi Asaf, Michal Canetti, Michael Edery, Shir Elimeleh, Ameen Masri, Grace Rabinowitz, Neta Silbermintz, Gabriel Zollmann and Haim Mayan
J. Clin. Med. 2026, 15(18), 6975; https://doi.org/10.3390/jcm15186975 - 9 Sep 2026
Abstract
Background/Objectives: Dehydration is an under-recognized cause of hypercalcemia, and no validated bedside marker exists to distinguish it from other etiologies. We evaluated the urinary calcium-to-creatinine ratio (uCa/Cr) and the fractional excretion of calcium (FeCa) as predictors of dehydration across a spectrum of hypercalcemic [...] Read more.
Background/Objectives: Dehydration is an under-recognized cause of hypercalcemia, and no validated bedside marker exists to distinguish it from other etiologies. We evaluated the urinary calcium-to-creatinine ratio (uCa/Cr) and the fractional excretion of calcium (FeCa) as predictors of dehydration across a spectrum of hypercalcemic and normocalcemic states. Methods: We conducted a retrospective cohort study of 96 patients admitted to an internal medicine ward with dehydration and/or hypercalcemia. Dehydration was identified using a combination of clinical criteria (presenting complaint, physical examination findings of volume depletion, and admitting physician assessment) and biochemical criteria (elevated plasma urea, creatinine, or sodium, or elevated urine osmolality). Patients were classified into three groups: non-dehydrated hypercalcemic (n = 37), dehydrated hypercalcemic (n = 24), and dehydrated normocalcemic (n = 35). Urinary analyses were performed on patients not receiving chronic diuretic therapy (n = 70 with complete data). Logistic regression, receiver operating characteristic (ROC) analysis, and CKD-stratified sensitivity analyses were performed. Results: uCa/Cr differed significantly across all three groups (medians 1.046, 0.484, and 0.056 mmol/mmol respectively; p < 0.001 for all pairwise comparisons). Hypocalciuria-defined as reduced urinary calcium excretion (uCa/Cr < 0.2 mmol/mmol)-was absent in non-dehydrated patients and present in 59.5% of dehydrated patients; this should not be confused with hypocalcemia (low serum calcium). ROC analysis yielded an AUC of 0.894 (95% CI: 0.819–0.969), significantly superior to FeCa (AUC 0.813; DeLong p = 0.012). At a threshold of 0.2 mmol/mmol, specificity and positive predictive value were both 100%. uCa/Cr remained independently associated with dehydration after adjustment for chronic kidney disease (CKD), age, and sex (OR 0.112, 95% CI: 0.030–0.307, p < 0.001). PTH suppression was significantly less frequent in dehydrated than non-dehydrated patients (24.4% vs. 51.5%, p = 0.018). Conclusions: Random uCa/Cr is a highly specific, CKD-independent predictor of dehydration. A uCa/Cr value below 0.2 mmol/mmol, particularly combined with non-suppressed PTH, should prompt consideration of dehydration as the primary cause of hypercalcemia. Full article
(This article belongs to the Section Nephrology & Urology)
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17 pages, 5942 KB  
Article
Pallidal Volumetry and Neutrophil-to-Lymphocyte Ratio in Differentiating Progressive Supranuclear Palsy from Parkinson’s Disease
by Bartosz Migda, Michał Kutyłowski, Natalia Madetko-Alster, Anna Migda, Karol Kutyłowski and Piotr Alster
Diseases 2026, 14(9), 330; https://doi.org/10.3390/diseases14090330 - 9 Sep 2026
Abstract
Background: Progressive supranuclear palsy (PSP) and Parkinson’s disease (PD) frequently present with overlapping clinical features, creating diagnostic challenges, particularly during the early stages of disease. Structural MRI and peripheral inflammatory biomarkers may provide complementary information for differential diagnosis. Objective: To evaluate the diagnostic [...] Read more.
Background: Progressive supranuclear palsy (PSP) and Parkinson’s disease (PD) frequently present with overlapping clinical features, creating diagnostic challenges, particularly during the early stages of disease. Structural MRI and peripheral inflammatory biomarkers may provide complementary information for differential diagnosis. Objective: To evaluate the diagnostic performance of automated pallidal volumetry and the neutrophil-to-lymphocyte ratio (NLR), individually and in combination, for distinguishing PSP from PD. Methods: This retrospective case–control study included 12 patients with PSP and 12 patients with PD. Automated brain volumetry was performed using the volBrain 2.0 platform. Total pallidal volume was selected as the primary imaging biomarker based on its established involvement in PSP pathology. NLR was calculated from routine blood counts. Diagnostic performance was assessed using receiver operating characteristic (ROC) analysis. A combined MRI–blood model was constructed using binary logistic regression. Results: Patients with PSP demonstrated lower normalized pallidal volumes than patients with PD. Pallidal volume showed high diagnostic performance for differentiating PSP from PD (AUC = 0.885), whereas NLR demonstrated only modest discriminatory ability (AUC = 0.715). The combined pallidal volume–NLR model achieved an AUC of 0.903 compared with 0.885 for pallidal volumetry alone, but this difference was not statistically significant (DeLong p = 0.732), and sensitivity, specificity and overall accuracy remained unchanged. Conclusions: Automated pallidal volumetry provided substantially better discrimination between PSP and PD than NLR alone. Although the combined model showed a small numerical increase in AUC, this improvement was not statistically significant and did not alter sensitivity, specificity or overall accuracy. These findings do not demonstrate incremental diagnostic value of NLR beyond pallidal volumetry in this cohort. Larger prospective studies are needed to determine the clinical utility of combined MRI–blood biomarker approaches in PSP. Full article
(This article belongs to the Section Neuro-psychiatric Disorders)
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19 pages, 866 KB  
Article
Serum Alpha-Klotho and Coronary Atherosclerosis: Associations with Coronary CT Angiography Findings and Atherogenic Indices
by Ayça Tuzcu, Mustafa Gök, Kenan Yörük, Mustafa Yılmaz, Ali Alkaşi and Göksel Tuzcu
Biomedicines 2026, 14(9), 2026; https://doi.org/10.3390/biomedicines14092026 - 9 Sep 2026
Abstract
Background/Objectives: Alpha-Klotho is a circulating protein with anti-aging and vasculoprotective properties that may play a role in vascular calcification. This study aimed to investigate the association between serum alpha-Klotho levels and coronary atherosclerotic burden assessed by the Agatston score and CAD-RADS grading, [...] Read more.
Background/Objectives: Alpha-Klotho is a circulating protein with anti-aging and vasculoprotective properties that may play a role in vascular calcification. This study aimed to investigate the association between serum alpha-Klotho levels and coronary atherosclerotic burden assessed by the Agatston score and CAD-RADS grading, as well as cardiometabolic risk indices. Methods: This single-center, prospective, cross-sectional study included 86 patients undergoing coronary computed tomography angiography. Serum alpha-Klotho levels were measured by ELISA. Associations with imaging and metabolic variables were assessed using Spearman correlation and age-adjusted partial correlation analyses. Independent associations were evaluated using multivariable linear regression with HC3-robust standard errors. Binary and ordinal logistic regression models with CAD-RADS as the dependent variable and receiver operating characteristic (ROC) analysis were additionally performed. Results: Serum Klotho levels were negatively correlated with age (ρ = −0.598), Agatston score (ρ = −0.540), and CAD-RADS (ρ = −0.549) (all p < 0.001). Associations with the Agatston score and CAD-RADS remained significant after age adjustment (ρ = −0.348 and −0.352, respectively). AIP also remained independently associated with Klotho after age adjustment (ρ = −0.289, p = 0.007), whereas associations with TyG and METS-IR were attenuated. Multivariable models explained 50–52% of the variance in Klotho. In ordinal logistic regression, Klotho remained independently associated with CAD-RADS severity after adjustment for age, sex, BMI, and AIP (OR = 0.525, p = 0.033). ROC analysis demonstrated moderate discrimination for the presence of coronary atherosclerosis, defined as Agatston score > 0 (equivalently, CAD-RADS > 0 in this cohort) (AUC = 0.754, 95% CI 0.654–0.855); an exploratory, internally derived cutoff of ≤823 pg/mL—not a clinically validated threshold—yielded 72.0% sensitivity and 75.0% specificity (bootstrap-validated optimism-corrected: 69.3% and 72.5%). Conclusions: Lower serum alpha-Klotho levels were independently associated with greater coronary atherosclerotic burden and showed moderate discriminative ability for its presence. These findings are preliminary and support further investigation of alpha-Klotho as a candidate circulating biomarker of coronary atherosclerosis, pending validation in larger, prospective cohorts. Full article
(This article belongs to the Special Issue Imaging Technology for Human Diseases: 2nd Edition)
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15 pages, 1318 KB  
Article
Diagnostic Performance of Serum Leucine-Rich Alpha-2-Glycoprotein 1 and Plasma Calprotectin in Adults with Suspected Acute Appendicitis: A Cross-Sectional Observational Study
by Lea Maršić, Zvjezdana Gvozdanović, Nikolina Farčić, Luka Maršić, Željka Dujmić, Željka Dragila Tomašić, Denis Klapan, Dino Vida, Josip Samardžić, Vikica Buljanović, Dag Dušanić, Andrea Saračević, Helena Čičak, Zrinka Mihaljević and Višnja Nesek Adam
Biomedicines 2026, 14(9), 2022; https://doi.org/10.3390/biomedicines14092022 - 8 Sep 2026
Abstract
Background/Objectives: This study evaluated the diagnostic performance of serum leucine-rich alpha-2-glycoprotein 1 (LRG1) and plasma calprotectin in adults with suspected acute appendicitis, compared them with routine inflammatory markers and clinical scores, and examined their association with abdominal guarding and the discrimination of uncomplicated [...] Read more.
Background/Objectives: This study evaluated the diagnostic performance of serum leucine-rich alpha-2-glycoprotein 1 (LRG1) and plasma calprotectin in adults with suspected acute appendicitis, compared them with routine inflammatory markers and clinical scores, and examined their association with abdominal guarding and the discrimination of uncomplicated from complicated appendicitis. Methods: Adults aged ≥18 years were enrolled in two Croatian emergency departments from April 2025 to March 2026. Acute appendicitis was histopathologically confirmed, whereas controls were defined by clinical follow-up or negative appendiceal histopathology. Biomarkers were measured using enzyme-linked immunosorbent assays, and diagnostic performance was assessed using receiver operating characteristic (ROC) analysis with area under the curve (AUC). Results: Among 126 patients, 62 (49.2%) had acute appendicitis and 64 (50.8%) were controls. Serum LRG1 was higher in patients with acute appendicitis than controls (27.4 μg/mL; IQR 25.3–28.0 vs. 23.2 μg/mL; IQR 17.6–27.8; p = 0.01), whereas plasma calprotectin did not differ. LRG1 was higher in cases with abdominal guarding (p = 0.02), but neither biomarker differed significantly between uncomplicated and complicated appendicitis. Conclusions: LRG1 showed limited diagnostic accuracy, while calprotectin showed no meaningful discrimination. The Adult Appendicitis Score and Appendicitis Inflammatory Response score outperformed both biomarkers. Full article
(This article belongs to the Section Molecular and Translational Medicine)
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22 pages, 2655 KB  
Article
Predicting Musculoskeletal Injury Risk in Professional Football Using a Supervised Machine Learning Approach Based on Full-Season Multi-Protocol Neuromuscular Assessments
by Daniel Rojas-Valverde, Jesús De Jorge, Rodrigo Yáñez-Sepúlveda and Aldo A. Vásquez-Bonilla
Data 2026, 11(9), 231; https://doi.org/10.3390/data11090231 - 8 Sep 2026
Abstract
Musculoskeletal injuries are the leading cause of time loss in professional football, yet machine learning models integrating multi-protocol force-plate data for injury-risk classification are absent from the Latin American professional football literature. Purpose: This study aims to develop and internally cross-validate a supervised [...] Read more.
Musculoskeletal injuries are the leading cause of time loss in professional football, yet machine learning models integrating multi-protocol force-plate data for injury-risk classification are absent from the Latin American professional football literature. Purpose: This study aims to develop and internally cross-validate a supervised Random Forest model for injury risk classification using full-season VALD ForceDecks data from a professional Costa Rican club, with thresholds derived from receiver operating characteristic (ROC) analyses. Methods: We utilized an observational longitudinal study (September 2024 to April 2026). One hundred and twenty-six male footballers from five competitive categories underwent 518 dual-force-plate assessments across four protocols (Nordic Hamstring, isometric mid-thigh pull, isometric adductor squeeze, countermovement jump), yielding 21 variables; one assessment per player entered the model. Record linkage against 262 surveillance-documented time-loss events identified 53 players with pre-injury assessments as the positive class (42.1%; ratio 1:1.4). SMOTE (k = 5) was applied within each training fold only. A Random Forest model (500 trees; depth 4) used 5-fold stratified cross-validation. The HIGH boundary was set at the Youden index, and the LOW boundary was set as the first score quartile. Results: The mean AUC-ROC across folds was 0.683 +/− 0.050, the only estimate of generalisation reported. Refitted on the complete dataset and applied back to the same players, the model gave at the Youden cut-point (score ≥ 45.2) an apparent sensitivity of 100% and specificity of 95.9%; these resubstitution values are optimistically biased. The leading predictors were Pull RFD (10.0%), CMJ power per body mass (7.2%) and eccentric CMJ peak force (6.6%). The risk tiers were HIGH 56 (44.4%), MEDIUM 39 (31.0%), and LOW 31 (24.6%). Conclusions: Multi-protocol force-plate data yield moderate internally cross-validated discrimination of injury risk. The near-perfect threshold metrics are apparent values, not generalisation performance. Rate of force development and eccentric force capacity outranked asymmetry indices. Prospective external validation is required before clinical use. Full article
(This article belongs to the Special Issue Big Data and Data-Driven Research in Sports)
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14 pages, 526 KB  
Article
Predictive Value of the ALBI Grade for Short-Term Morbidity and Mortality After Pancreatoduodenectomy
by Ali Ramouz, Abdulelah Al-Ahdal, Carl-Stephan Leonhardt, Georgios Polychronidis, Thomas Hank, Arianeb Mehrabi, Oliver Strobel, Martin Loos, Markus W. Büchler, Zoltan Czigany and Mohammed Al-Saeedi
Cancers 2026, 18(17), 2897; https://doi.org/10.3390/cancers18172897 - 7 Sep 2026
Abstract
Background: Pancreatoduodenectomy (PD) is a complex surgical procedure with substantial postoperative morbidity and mortality. Postoperative outcomes following PD are typically determined by measuring preoperative liver function in the form of serum albumin and bilirubin levels. In this study, the prognostic value of [...] Read more.
Background: Pancreatoduodenectomy (PD) is a complex surgical procedure with substantial postoperative morbidity and mortality. Postoperative outcomes following PD are typically determined by measuring preoperative liver function in the form of serum albumin and bilirubin levels. In this study, the prognostic value of the preoperative ALBI grade was compared with that of albumin and bilirubin alone in predicting postoperative complications and short-term mortality after PD. Methods: This retrospective cohort study included 1149 patients who underwent partial or total PD between 2014 and 2017 at a high-volume surgical center. The preoperative ALBI grade (I–III) was calculated in these patients as well as the preoperative levels of bilirubin and albumin. The associations between ALBI grade, albumin and bilirubin levels with postoperative complications and 30- and 90-day mortality were analyzed using univariate and multivariable logistic regression models. The predictive performance of the ALBI grade and albumin and bilirubin levels was assessed using receiver operating characteristic (ROC) curves and area under the curve (AUC) analysis. Results: Higher ALBI grades were significantly associated with worse perioperative outcomes, including increased incidence of liver perfusion failure (42.4%) and postpancreatectomy hemorrhage (15.2%). In a pre-specified reduced multivariable model adjusted for BMI, ASA physical status as well as surgical complexity, ALBI grade III remained associated with 30- and 90-day mortality (OR 6.21; 95% CI, 1.62–23.78; p = 0.008 and OR 8.97; 95% CI, 2.91–27.62; p < 0.001) but was attenuated compared to univariate analyses. Seven of the 8 patients with ASA grade IV physical status were in ALBI grade III and accounted for 5 of the 6 30-day and 6 of the 8 90-day deaths in this group; in a sensitivity analysis excluding these patients, the association between ALBI grade III and 30-day mortality was no longer statistically significant, and the univariable association with 90-day mortality was also attenuated to non-significance, although the BMI-adjusted 90-day estimate remained significant (OR 5.02; 95% CI, 1.07–23.54; p = 0.041). ROC analysis showed that the ALBI score (AUC, 0.74 and 0.74) did not outperform albumin alone (AUC, 0.69 and 0.70) in predicting 30- and 90-day mortality (DeLong p = 0.21–0.24), although both outperformed bilirubin alone (AUC, 0.54–0.56). Conclusions: Preoperative ALBI grade III is associated with short-term morbidity and mortality after PD, but this association is confounded in part by baseline surgical risk (ASA physical status), and the ALBI score does not outperform albumin alone as a predictor of mortality. As a simple, readily available composite marker, the ALBI grade may still help flag patients who warrant closer perioperative surveillance, although this retrospective study does not establish that correcting albumin or bilirubin levels before surgery improves outcomes. Full article
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9 pages, 235 KB  
Article
A Height-Normalised Revised Drowning Index for Thoracic Fluid Burden: Associations with Water Type, Sex, Toxicology and Postmortem Interval
by Eva Montanari, Cristian D’Ovidio, Tommaso D’Anna, Emina Dervišević, Claudia Rosa, Mariu Alexandru Apostol, Alberto Salomone, Enrico Gerace, Ismail Ozgur Can, Roberto Campagna and Angelo Montana
Diagnostics 2026, 16(17), 2870; https://doi.org/10.3390/diagnostics16172870 - 7 Sep 2026
Abstract
Background: The forensic diagnosis of drowning lacks pathognomonic signs, and visceral weight-based indices normalised to spleen or heart weight have shown variable discriminant performance. We assessed a height-normalised revised Drowning Index (rDI) as a measure of thoracic fluid burden in confirmed drowning cases, [...] Read more.
Background: The forensic diagnosis of drowning lacks pathognomonic signs, and visceral weight-based indices normalised to spleen or heart weight have shown variable discriminant performance. We assessed a height-normalised revised Drowning Index (rDI) as a measure of thoracic fluid burden in confirmed drowning cases, not as a case–control test of drowning versus non-drowning deaths. Methods: Fifty-five institutional drowning cases (Ancona and Turin Province, Italy, 2008–2020) were analysed. The rDI and the original spleen-normalised Drowning Index (DI) were calculated. A multivariable linear regression assessed sex, water type, and toxicological status as simultaneous covariates; a receiver operating characteristic (ROC) analysis evaluated the within-cohort classification of water type; and the associations with the postmortem interval (PMI) were explored separately. Results: The rDI was independently associated with the male sex (standardised β = 0.391, p = 0.002) and saltwater drowning (β = 0.331, p = 0.011; adjusted R2 = 0.269). The three benzodiazepine-positive institutional cases had a lower rDI in the univariate analysis (p = 0.019), but the association was not retained in the multivariable model or in a freshwater-restricted sensitivity analysis. Alcohol exposure showed no association. The water-type ROC analysis yielded an area under the curve of 0.727 (95% CI 0.553–0.871); the distributions overlapped substantially. The original DI was not associated with the variables studied. The rDI showed no significant association with the PMI within the range represented by all but one case (1–12 days). Conclusions: The rDI quantified the variation in the thoracic fluid burden within this cohort of confirmed drownings and showed moderate, exploratory water-type classification. It is not a stand-alone diagnostic test, and its discrimination ability between drowning and non-drowning deaths was not assessed. Dedicated case–control and external validation studies are required before forensic cut-offs can be recommended. Full article
(This article belongs to the Section Forensic Diagnostics)
15 pages, 5812 KB  
Article
Microfluidic Light-Scattering Imaging Coupled with Deep Learning for Label-Free Single-Cell Classification of Lymphoma Cells
by Linyan Xie, Mengfei Wang, Xijia Luo, Shuoxian Xia, Qiongqiong Ren and Xuezhi Zhou
Biosensors 2026, 16(9), 500; https://doi.org/10.3390/bios16090500 - 7 Sep 2026
Abstract
Accurate classification of lymphoma cell subtypes is essential for disease diagnosis and therapeutic decision-making, yet conventional approaches often rely on fluorescence labeling, labor-intensive sample preparation, and specialized instrumentation, limiting their applicability for rapid, label-free single-cell analysis. Here, we present an AI-assisted microfluidic light-scattering [...] Read more.
Accurate classification of lymphoma cell subtypes is essential for disease diagnosis and therapeutic decision-making, yet conventional approaches often rely on fluorescence labeling, labor-intensive sample preparation, and specialized instrumentation, limiting their applicability for rapid, label-free single-cell analysis. Here, we present an AI-assisted microfluidic light-scattering imaging platform for label-free classification of lymphoma cells. The platform integrates hydrodynamic focusing within a microfluidic chip, continuous acquisition of two-dimensional (2D) light-scattering patterns, automated image preprocessing, and transfer learning based on a pretrained ResNet50 network for intelligent optical feature extraction and classification. Human B lymphoma (Daudi) and T lymphoblastic lymphoma (SUP-T1) cells were used to evaluate the proposed framework. The optical imaging system was first validated using standard microspheres, demonstrating reliable acquisition of light-scattering patterns under continuous-flow conditions. A dataset comprising 800 single-cell scattering patterns was subsequently established and evaluated using stratified five-fold cross-validation. The proposed framework achieved an average classification accuracy of 94.75% with an average area under the receiver operating characteristic (ROC) curve of 0.986. By integrating microfluidic optical biosensing with deep learning, this work enables automated interpretation of intrinsic optical scattering signatures and provides a promising AI-enabled strategy for rapid, label-free lymphoma screening and intelligent healthcare applications. Full article
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17 pages, 2113 KB  
Article
Insulin Tolerance Test in Adult GH Deficiency: An Exploratory Study Deriving BMI-Dependent Cut-Offs Using a Clinical Reference Standard
by Daniela Cuboni, Francesca Mocellini, Michela Sibilla, Giada De Lauro, Emanuele Varaldo, Alessandro Maria Berton, Nunzia Prencipe, Ezio Ghigo, Silvia Grottoli, Mauro Maccario and Valentina Gasco
Biomedicines 2026, 14(9), 2001; https://doi.org/10.3390/biomedicines14092001 - 5 Sep 2026
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Abstract
Background: The diagnosis of adult growth hormone (GH) deficiency (GHD) relies on demonstrating a reduced GH response to stimulation tests. Excess body weight, an increasingly prevalent condition, is associated with a blunted GH response to all types of stimulation tests. Therefore, establishing [...] Read more.
Background: The diagnosis of adult growth hormone (GH) deficiency (GHD) relies on demonstrating a reduced GH response to stimulation tests. Excess body weight, an increasingly prevalent condition, is associated with a blunted GH response to all types of stimulation tests. Therefore, establishing body mass index (BMI)-dependent cut-offs is essential for accurate interpretation. This study aimed to identify BMI-specific diagnostic thresholds for the insulin tolerance test (ITT), using residual pituitary function as the clinical gold standard. Methods: We retrospectively analyzed 105 patients with hypothalamic-pituitary disorders who underwent ITT. GHD was defined by the presence of at least three pituitary hormone deficiencies, while preserved somatotropic function was defined by the absence of other pituitary deficits and an insulin-like growth factor-I (IGF-I) standard deviation score ≥ 0. Receiver operating characteristic (ROC) curve analysis was used to determine optimal BMI-stratified cut-offs, defined as those maximizing sensitivity (SE) and specificity (SP). Results: The optimal GH cut-off was 2.8 μg/L for patients with normal weight (SE 84.6%, SP 97.4%) and those with overweight (SE 100%, SP 92.3%), and 2.1 μg/L for patients with obesity (SE 88.2%, SP 87.5%). The area under the ROC curve was 0.968, 0.957, and 0.897 for patients with normal weight, overweight, and obesity, respectively. Conclusions: This is the first study to define GH diagnostic thresholds for the ITT according to BMI, using a clinical definition of GHD as reference. More restrictive cut-offs in patients with obesity are needed to avoid GHD overdiagnosis and potential overtreatment. These findings should be considered hypothesis-generating and require prospective external validation before routine clinical implementation. Full article
(This article belongs to the Section Endocrinology and Metabolism Research)
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22 pages, 724 KB  
Article
Discriminatory Capacity of Anthropometric Indicators and Physical Fitness Tests for Identifying Waist-to-Height Ratio-Defined Cardiometabolic Risk in Adolescents According to Sex and Biological Maturity
by Victoria López-Lombó, Adrián Mateo-Orcajada, Lucía Abenza-Cano, J. Arturo Abraldes, Mario Albaladejo-Saura and Raquel Vaquero-Cristóbal
Children 2026, 13(9), 1201; https://doi.org/10.3390/children13091201 - 5 Sep 2026
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Abstract
Background/Objectives: Field-based health screening in adolescents requires accurate, non-invasive, and feasible diagnostic tools. This study evaluated the discriminatory capacity of anthropometric parameters and physical fitness tests for identifying waist-to-height ratio (WHtR)-defined surrogate cardiometabolic risk across sex and biological maturity status, determining exploratory cut-off [...] Read more.
Background/Objectives: Field-based health screening in adolescents requires accurate, non-invasive, and feasible diagnostic tools. This study evaluated the discriminatory capacity of anthropometric parameters and physical fitness tests for identifying waist-to-height ratio (WHtR)-defined surrogate cardiometabolic risk across sex and biological maturity status, determining exploratory cut-off thresholds. Methods: A cross-sectional study was conducted with 2944 Spanish adolescents (1459 males, 1485 females; age: 13.35 ± 1.20 years). Anthropometric variables (BMI, skinfolds, fat/muscle mass) and physical fitness tests (20-m shuttle run, handgrip, CMJ, SBJ, 20-m sprint, curl-up; evaluated in raw and body-mass-normalized formats) were assessed. Biological maturation was estimated via Age at Peak Height Velocity (APHV) using Mirwald equations and categorized into early, on-time, and late maturers relative to the sample mean. Surrogate risk was operationalized strictly as WHtR ≥ 0.50, without direct assessment of biochemical or hemodynamic parameters. Receiver operating characteristic (ROC) curves, optimal Youden-derived cut-offs, and internal bootstrap validation (1000 resamples) were performed. Results: Anthropometric parameters demonstrated high discriminatory performance for detecting WHtR-defined surrogate risk across all sex and maturation cohorts (AUC = 0.88–0.98). Unadjusted physical fitness tests showed poor overall classification performance. However, normalizing fitness metrics for body mass (particularly relative CMJ and cardiorespiratory fitness) substantially improved discriminatory capacity. Optimal cut-off values for anthropometric indicators displayed an observed descending pattern across progressively later-maturing cohorts. Conclusions: Anthropometric parameters represent highly accurate field proxies for WHtR-defined surrogate risk screening in adolescents. While unadjusted fitness metrics have limited utility for this anthropometric outcome, body-mass-normalized fitness parameters substantially recover classification capacity. Biological maturation timing should be carefully considered when future research derives and externally validates adolescent screening thresholds, as current cut-offs remain exploratory and sample-derived. Full article
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12 pages, 1236 KB  
Article
Differences in Chronic Pulmonary Embolism Burden in Chronic Thromboembolic Disease with and Without Pulmonary Hypertension
by Colin McQuade, Dayana Davoudi, Katherine Lajkosz, Laura Donahoe, John Granton, Marc de Perrot and Micheal McInnis
J. Clin. Med. 2026, 15(17), 6878; https://doi.org/10.3390/jcm15176878 - 5 Sep 2026
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Abstract
Background: Chronic thromboembolic disease is a recognised sequela of acute pulmonary embolism and may occur with or without pulmonary hypertension. The purpose of this study was to evaluate differences in chronic thromboembolic burden, lesion type, and distribution between chronic thromboembolic pulmonary disease [...] Read more.
Background: Chronic thromboembolic disease is a recognised sequela of acute pulmonary embolism and may occur with or without pulmonary hypertension. The purpose of this study was to evaluate differences in chronic thromboembolic burden, lesion type, and distribution between chronic thromboembolic pulmonary disease without pulmonary hypertension (CTEPD) and chronic thromboembolic pulmonary hypertension (CTEPH). Methods: This retrospective single-centre study included patients with CTEPD or CTEPH by right heart catheterisation using 2022 ESC/ERS criteria between 2021 and 2022. Two CTEPH patients were randomly selected per CTEPD patient. CTPA studies were reviewed by a blinded thoracic radiologist, assessing 32 pulmonary vessels from the main to segmental arteries for chronic thromboembolic lesions. Groups were compared by disease distribution, most proximal lesion level, Qanadli obstruction index, lesion type, and location. Exploratory receiver operating characteristic (ROC) analysis assessed discriminatory performance. Results: The 44 CTEPD and 88 CTEPH patients included had no differences in age, BMI, or sex. CTEPH patients had shorter six-minute walk distance (p = 0.001), greater right ventricular dilation/dysfunction (p < 0.001), and lower prevalence of deep vein thrombosis (p = 0.03). CTPA identified more lesions in CTEPH (21.2 vs. 10.0 lesions/case, p < 0.001) across more lobes (4.8 vs. 3.4, p < 0.001), with more proximal main/lobar disease (p < 0.001). CT obstruction index was 51% in CTEPH and 26% in CTEPD (p < 0.001). Total lesion number best discriminated CTEPH from CTEPD (AUC 0.91; optimal cutoff, 16 lesions). Conclusions: CTEPH demonstrates a greater, more diffuse, and more proximal chronic thromboembolic lesion burden on CTPA than CTEPD. Full article
(This article belongs to the Section Respiratory Medicine)
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15 pages, 633 KB  
Article
Association Between the Triglyceride-to-HDL Cholesterol Ratio and Glycemic Control in Patients with Type 2 Diabetes Mellitus: A Real-World Retrospective Study
by Ali Erol and Muhammet Fatih Şahin
Biomedicines 2026, 14(9), 1995; https://doi.org/10.3390/biomedicines14091995 - 4 Sep 2026
Viewed by 197
Abstract
Background and Objectives: The triglyceride-to-high-density lipoprotein cholesterol ratio (TG/HDL-C) is a simple lipid index associated with insulin resistance and atherogenic dyslipidemia. Previous evidence has supported the TG/HDL-C ratio as a simple surrogate marker of insulin resistance and an adverse metabolic profile. However, [...] Read more.
Background and Objectives: The triglyceride-to-high-density lipoprotein cholesterol ratio (TG/HDL-C) is a simple lipid index associated with insulin resistance and atherogenic dyslipidemia. Previous evidence has supported the TG/HDL-C ratio as a simple surrogate marker of insulin resistance and an adverse metabolic profile. However, its relationship with glycemic control in real-world patients with type 2 diabetes mellitus (T2DM) remains uncertain. This study evaluated the association between the TG/HDL-C ratio and poor glycemic control in patients with T2DM. Materials and Methods: This retrospective observational study included patients with T2DM followed in outpatient clinics. Poor glycemic control was defined as glycated hemoglobin A1c (HbA1c) ≥ 7%. The association between the TG/HDL-C ratio and glycemic control was assessed using group comparisons, Spearman correlation, tertile analysis, and multivariable logistic regression adjusted for age, sex, LDL-C, total cholesterol, insulin use, statin use, and fenofibrate use. Receiver operating characteristic (ROC) analysis was used to evaluate the discriminatory performance of the TG/HDL-C ratio for identifying poor glycemic control. A sensitivity analysis was performed after excluding patients receiving fenofibrate. Results: A total of 1001 patients with T2DM were included, of whom 568 (56.7%) had poor glycemic control. The mean age was 60.9 ± 11.4 years, and 57.1% of participants were women. The poor- and adequate-glycemic-control groups were comparable with respect to age and sex. The TG/HDL-C ratio was higher in patients with HbA1c ≥7% than in those with HbA1c < 7% [3.35 (2.35–5.00) vs. 2.74 (1.87–3.82), p < 0.001] and increased progressively across tertiles. In multivariable analysis, the TG/HDL-C ratio remained associated with poor glycemic control after adjustment for available covariates (OR: 1.201, 95% CI: 1.125–1.282, p < 0.001). The association remained significant after excluding fenofibrate users. ROC analysis showed modest discrimination (AUC: 0.601, 95% CI: 0.566–0.636). Conclusions: The TG/HDL-C ratio was associated with poor glycemic control in patients with T2DM, showing a graded association across tertiles. However, its standalone discriminatory performance is modest. Given its modest discriminatory performance, the TG/HDL-C ratio should not be considered a standalone diagnostic or predictive tool for poor glycemic control; rather, it may serve as an accessible adjunctive metabolic marker associated with an adverse glycemic and lipid profile. Full article
(This article belongs to the Special Issue Molecular Insights and Advances in Metabolic Disorders)
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