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23 pages, 1805 KB  
Article
Baseline Neurological Severity and Early Imaging Findings Predict 3-Month Functional Outcome in Anterior-Circulation Acute Ischemic Stroke: A Retrospective Cohort Study with One-Year Follow-Up
by Abdullah Güzel, Elif Simin Issı, Sinem Yorgancı Ulaş, Usame Rakip and Ayşe Ertekin
J. Clin. Med. 2026, 15(15), 6016; https://doi.org/10.3390/jcm15156016 - 2 Aug 2026
Abstract
Background: Bedside prognostication after acute ischemic stroke remains challenging despite the availability of several composite scores, which often demand variables not routinely obtained at admission. Whether the combination of baseline neurological severity and early non-contrast computed tomography findings can support parsimonious, contemporaneous prediction [...] Read more.
Background: Bedside prognostication after acute ischemic stroke remains challenging despite the availability of several composite scores, which often demand variables not routinely obtained at admission. Whether the combination of baseline neurological severity and early non-contrast computed tomography findings can support parsimonious, contemporaneous prediction of 3-month functional outcome is an open question, particularly given the well-documented overlap between clinical and imaging measures of stroke extent. Methods: We retrospectively analyzed 432 consecutive adults admitted with confirmed anterior-circulation acute ischemic stroke to a Turkish tertiary care university hospital between January 2022 and December 2025. The primary outcome was a poor functional outcome, defined as modified Rankin Scale (mRS) score 3–6 at 3 months. A prespecified multivariable logistic regression model incorporated three admission variables: baseline National Institutes of Health Stroke Scale (NIHSS) per five-point increment, Alberta Stroke Program Early CT Score (ASPECTS) per one-point increment, and age dichotomized at 65 years. Model performance was assessed with the area under the receiver operating characteristic curve (AUC), five-fold stratified cross-validation, and calibration testing. We additionally performed DeLong tests, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) analyses to evaluate the incremental contribution of ASPECTS, and compared the parsimonious model against a comprehensive multivariable model containing ten predictors. Results: At 3 months, 252 patients (58.3%) had poor functional outcome, with 177 deaths (41.0%). Baseline NIHSS emerged as the dominant predictor (adjusted odds ratio [aOR] 4.16 per five-point increase, 95% confidence interval [CI] 2.79–6.22, p < 0.001), whereas ASPECTS retained no independent prognostic value after adjustment (aOR 0.99 per point, 95% CI 0.73–1.34, p = 0.952). Age ≥ 65 years was likewise non-significant (aOR 0.79, 95% CI 0.46–1.37, p = 0.405). The parsimonious model achieved excellent discrimination (AUC 0.904, 95% CI 0.876–0.932; cross-validated AUC 0.899, 95% CI 0.873–0.926) and good overall calibration on internal validation (calibration slope 0.958; calibration-in-the-large 0.009), although the Hosmer–Lemeshow test was significant (p = 0.001), reflecting localized miscalibration in the intermediate-risk range. Adding ASPECTS to a reduced model containing only NIHSS and age produced no meaningful discrimination gain (ΔAUC + 0.0003, DeLong p = 0.50; IDI ≈ 0), consistent with substantial variance sharing between NIHSS and ASPECTS (Spearman ρ = −0.89). A comprehensive model including infarct volume, Glasgow Coma Scale, reperfusion therapy, and comorbidities did not improve discrimination (AUC 0.905) and yielded a worse Akaike information criterion, supporting the sufficiency of the parsimonious model. Conclusions: In this Turkish tertiary center cohort, baseline NIHSS captured most of the prognostic information available at admission, and early ASPECTS added minimal independent value once neurological severity was accounted for. Findings should be interpreted in the context of the high case-mix severity of this referral population; external validation in independent, multicenter cohorts is required before clinical implementation is considered. Full article
(This article belongs to the Section Clinical Neurology)
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27 pages, 1362 KB  
Article
Body Roundness Index and A Body Shape Index as First-Trimester Risk-Stratification Markers for Gestational Diabetes in Overweight Pregnant Women Without Established Major Risk Factors: A Prospective Single-Center Cohort Study
by Ömer Osman Eroğlu, Cansın Eroğlu, Sait Erbey, Murat Polat, Bilge Erbey, Mehmet Alican Sapmaz and Çağanay Soysal
Diagnostics 2026, 16(15), 2384; https://doi.org/10.3390/diagnostics16152384 - 29 Jul 2026
Viewed by 186
Abstract
Background/Objectives: Universal screening for gestational diabetes mellitus (GDM) is performed at 24–28 gestational weeks, but recommendations for earlier risk stratification differ across guidelines. Overweight pregnant women (body mass index [BMI] 25.0–29.9 kg/m2) without established major GDM risk factors constitute a clinical [...] Read more.
Background/Objectives: Universal screening for gestational diabetes mellitus (GDM) is performed at 24–28 gestational weeks, but recommendations for earlier risk stratification differ across guidelines. Overweight pregnant women (body mass index [BMI] 25.0–29.9 kg/m2) without established major GDM risk factors constitute a clinical gray zone for which current guidelines provide no explicit directive. We evaluated the first-trimester diagnostic performance of two composite anthropometric indices—the Body Roundness Index (BRI) and A Body Shape Index (ABSI)—for subsequent IADPSG-defined GDM within this specific clinical niche. Methods: This prospective single-center cohort study enrolled 198 consecutive overweight pregnant women without major GDM risk factors at 11 + 0 to 13 + 6 gestational weeks; 186 participants completed the 75 g OGTT at 24–28 weeks and were analyzed. Anthropometric measurements were obtained by trained nurses blinded to outcome. Glucose was assayed by hexokinase enzymatic reference method (intra-assay CV ≤ 1.5%). Discrimination, calibration, reclassification (NRI, IDI), decision curve analysis, and three independent internal validation procedures were performed. Results: GDM prevalence was 18.28% (34/186). BRI achieved an AUC of 0.905 (95% CI 0.835–0.974) and ABSI an AUC of 0.889 (95% CI 0.815–0.963), both significantly greater than BMI (AUC 0.705; DeLong p < 0.001). The optimal BRI cutoff of 4.45—interpreted as a cohort-specific analytic anchor rather than a transferable clinical threshold—yielded 85.3% sensitivity and 90.8% specificity. Adding BRI to BMI improved discrimination by 45.6% (IDI). Bootstrap optimism remained below 0.01 across all models. Conclusions: Following internal validation through bootstrap optimism correction and cross-validation, first-trimester BRI and ABSI provided strong supplementary risk stratification for GDM in overweight pregnant women without major risk factors. External validation in independent populations is required before clinical implementation. Full article
(This article belongs to the Special Issue Advanced Diagnostics in Women's Health: From Biomarkers to Imaging)
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15 pages, 1588 KB  
Article
Serum Urate as a Cardiometabolic Risk Enhancer Beyond SCORE2 in Psoriatic Arthritis
by Lilyan C. Charca, Marta Loredo, Estefanía Pardo, Ignacio Braña, Stefanie Burger, Paula Alvarez and Rubén Queiro
J. Clin. Med. 2026, 15(15), 5788; https://doi.org/10.3390/jcm15155788 - 24 Jul 2026
Viewed by 201
Abstract
Background/Objectives: Cardiovascular risk (CVR) prediction using SCORE2 may incompletely capture the burden of subclinical atherosclerosis in patients with chronic inflammatory conditions. Identifying simple, accessible markers to refine risk stratification remains an unmet need. This study aimed to evaluate whether serum urate improves detection [...] Read more.
Background/Objectives: Cardiovascular risk (CVR) prediction using SCORE2 may incompletely capture the burden of subclinical atherosclerosis in patients with chronic inflammatory conditions. Identifying simple, accessible markers to refine risk stratification remains an unmet need. This study aimed to evaluate whether serum urate improves detection of subclinical atherosclerosis beyond SCORE2 in a psoriatic arthritis cohort. Methods: We conducted a cross-sectional study including 250 patients with psoriatic arthritis fulfilling CASPAR criteria. Vascular assessment comprised carotid and femoral ultrasound and abdominal radiography. Atherosclerotic plaque was defined according to Mannheim criteria. The main outcomes were global plaque (≥1 vascular territory) and extended plaque (≥2 territories). Multivariable logistic regression adjusted for SCORE2 categories assessed independent associations. Incremental value was evaluated using decision curve analysis (DCA), category-free net reclassification improvement (cfNRI), and integrated discrimination improvement (IDI). Results: Hyperuricemia prevalence was 21.6%. Patients with hyperuricemia showed a higher prevalence of global plaque (88.9% vs. 62.8%, p < 0.001). After adjustment for SCORE2, serum urate was independently associated with global plaque (OR 4.23, 95% CI 1.26–14.2). Notably, 64.3% of patients classified as low–moderate risk already exhibited plaque. In the 50–69-year subgroup, adding serum urate improved reclassification (cfNRI +0.60; IDI +0.031) and was associated with higher net clinical benefit across decision thresholds. The combined model (SCORE2+HU+cIMT) achieved the highest curves, although with limited incremental gain over HU alone. Conclusions: SCORE2 categories showed substantial discordance with imaging-defined subclinical atherosclerotic burden in this population. Serum urate, an inexpensive and widely available marker, may help refine cardiovascular risk stratification and identify patients who could benefit from further vascular assessment. Full article
(This article belongs to the Special Issue Cardiovascular Risks in Autoimmune and Inflammatory Diseases)
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19 pages, 4586 KB  
Article
Prognostic Significance of the CALM Index in Surgically Resected Non-Small Cell Lung Cancer
by Soomin An, Wankyu Eo, Sookyung Lee and Dae Hyun Kim
J. Clin. Med. 2026, 15(15), 5772; https://doi.org/10.3390/jcm15155772 - 23 Jul 2026
Viewed by 222
Abstract
Background: Anatomical staging is often insufficient for predicting outcomes in stage I-IIIA non-small cell lung cancer (NSCLC) patients after curative resection due to inherent prognostic variability. In this study, we evaluated the prognostic value of the C-reactive protein–albumin–lymphocyte–monocyte (CALM) index as an [...] Read more.
Background: Anatomical staging is often insufficient for predicting outcomes in stage I-IIIA non-small cell lung cancer (NSCLC) patients after curative resection due to inherent prognostic variability. In this study, we evaluated the prognostic value of the C-reactive protein–albumin–lymphocyte–monocyte (CALM) index as an integrative biomarker for overall survival (OS). Methods: This retrospective study included 533 patients with stage I-IIIA NSCLC. We assessed the association between the CALM index and OS using multivariable Cox proportional hazards models, adjusted for established clinicopathological factors. We employed LASSO-penalized regression to optimize variable selection and ensure model stability. Comprehensive performance metrics were calculated, including Harrell’s C-index, integrated area under the curve (iAUC), integrated discrimination improvement (IDI), and decision-curve analysis (DCA). Results: The CALM index was identified as a stable, independent predictor of OS across both conventional and LASSO-penalized models. The final multivariable model incorporated the CALM index alongside age, pathological stage, American Society of Anesthesiologists status, pleural invasion, and the modified Shine–Lal index. Incorporation of the CALM index significantly enhanced model discrimination and risk reclassification at 3 and 5 years, while consistently increasing net clinical benefit across a wide range of threshold probabilities. Conclusions: The CALM index is a biologically plausible, robust, and readily accessible prognostic biomarker that provides incremental prognostic information beyond established factors in patients with resected stage I-IIIA NSCLC. Its integration into postoperative assessment offers a framework for refined prognostic stratification and more individualized clinical decision-making. Full article
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12 pages, 900 KB  
Article
Apolipoprotein B/A1 Ratio Improves Discrimination of Severe Atherosclerosis Beyond Conventional Lipid Markers in High-Risk Statin-Naive Patients
by Taedong Ok, Woo-Ri Lee, Sung Hun Kim and Kwon-Duk Seo
J. Clin. Med. 2026, 15(14), 5598; https://doi.org/10.3390/jcm15145598 - 16 Jul 2026
Viewed by 250
Abstract
Background/Objectives: The apolipoprotein B to apolipoprotein A1 (ApoB/A1) ratio has been proposed as a marker of cardiovascular risk, but its value for assessing extracranial and intracranial atherosclerosis beyond conventional lipid markers remains uncertain. We evaluated whether the ApoB/A1 ratio improves discrimination of severe [...] Read more.
Background/Objectives: The apolipoprotein B to apolipoprotein A1 (ApoB/A1) ratio has been proposed as a marker of cardiovascular risk, but its value for assessing extracranial and intracranial atherosclerosis beyond conventional lipid markers remains uncertain. We evaluated whether the ApoB/A1 ratio improves discrimination of severe atherosclerosis in high-risk statin-naive patients. Methods: We retrospectively included 3416 statin-naive patients who underwent lipid profiling and carotid duplex ultrasonography and/or cerebrovascular imaging between 2014 and 2023. The primary outcome was stenosis severity, categorized as normal, mild (<50% stenosis), or severe (≥50% stenosis, including occlusion), based on clinical imaging reports. Secondary outcomes were carotid plaque score and the number of stenotic intracranial vessels. Associations were assessed using multivariable ordinal logistic regression with 1-SD–standardized lipid markers. Results: The ApoB/A1 ratio was independently associated with greater stenosis severity (adjusted odds ratio 1.24 per 1-SD increase, 95% CI 1.15–1.35; p < 0.0001). Adding ApoB/A1 to a model including clinical covariates, LDL-C, and HDL-C significantly improved discrimination of severe stenosis on every metric examined (continuous NRI +0.142, 95% CI 0.053–0.227; IDI +0.0058, 0.0026–0.0088; likelihood ratio p = 0.0004), although the absolute increase in AUC was modest (0.660 to 0.668; ΔAUC +0.008; DeLong p = 0.026). Associations were consistent for carotid plaque score and intracranial vessel-count outcomes. Conclusions: In high-risk statin-naive patients undergoing carotid or cerebrovascular evaluation, the ApoB/A1 ratio was independently associated with atherosclerosis severity and provided modest incremental discrimination beyond conventional lipid markers. Apolipoprotein assessment may help refine risk stratification in this population. Full article
(This article belongs to the Section Clinical Neurology)
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30 pages, 7181 KB  
Article
Molecular Mechanisms of Oil and Saponin Accumulation and the Regulation of Carbohydrate Metabolism in Sapindus mukorossi Fruit
by Xiao Zhou, Changzhu Li, Yunzhu Chen, Yan Yang, Qiang Liu, Wenbin Zeng, Luhong Zhang, Lijuan Jiang, Zhihong Xiao, Yuena Ji, Li Li, Hao Wang, Peiwang Li and Jingzhen Chen
Plants 2026, 15(14), 2173; https://doi.org/10.3390/plants15142173 - 15 Jul 2026
Viewed by 265
Abstract
Sapindus mukorossi, known as soapberry, is a multipurpose woody species with oil-rich kernels and saponin-rich pulp, and its kernel oil and pulp saponins have important applications in oleochemicals, detergents, cosmetics, pharmaceuticals, and bioenergy. However, the mechanism by which carbohydrate-derived carbon is differentially [...] Read more.
Sapindus mukorossi, known as soapberry, is a multipurpose woody species with oil-rich kernels and saponin-rich pulp, and its kernel oil and pulp saponins have important applications in oleochemicals, detergents, cosmetics, pharmaceuticals, and bioenergy. However, the mechanism by which carbohydrate-derived carbon is differentially allocated to kernel oil biosynthesis and pulp saponin biosynthesis within the same fruit remains unclear. In this study, we integrated morphological, physiological, metabolomic, and transcriptomic analyses to investigate the developmental accumulation patterns of oil and saponins and their relationship with carbohydrate metabolism in S. mukorossi fruit. The fruit reached maturity at approximately 130 days after flowering and was divided into four developmental stages: slow growth, rapid expansion, color transition, and maturation. Kernel oil accumulated in a typical S-shaped pattern and increased rapidly during the middle-to-late developmental stages, whereas pulp saponins increased continuously before maturity and remained stable. At maturity, soluble sugars mainly accumulated in the pulp, while starch was relatively enriched in the kernels, indicating different carbohydrate storage and utilization patterns between the two tissues. Integrated transcriptomic and metabolomic analyses revealed tissue-specific metabolic regulation: lipid metabolism was preferentially enriched in kernels, whereas terpenoid and secondary metabolic pathways were more active in pulp. Several genes related to fatty acid assembly and oil accumulation, including SmACC, SmLACS, SmGPAT, and SmLPAT, showed kernel-biased expression, while genes involved in the mevalonate (MVA)-dependent triterpenoid saponin pathway, including SmACCT, SmMVK, SmIDI, SmSQE, and SmLUP2, were closely associated with pulp saponin accumulation. Hormone-related transcription factors, such as GRAS and BES1 in kernels and MYC2 in pulp, may contribute to the coordination between carbohydrate metabolism and oil or saponin biosynthesis. Overall, these findings suggest that oil and saponin accumulation in S. mukorossi fruit are regulated by distinct tissue-specific metabolic programs closely linked to carbohydrate metabolism. This study provides new insights into carbon allocation between kernel oil and pulp saponin biosynthesis and identifies candidate pathways and genes for the genetic improvement and resource utilization of S. mukorossi. Full article
(This article belongs to the Special Issue Biological Value of Plant Metabolites)
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20 pages, 1474 KB  
Article
Red Cell Distribution Width–Standard Deviation and the Severity of In-Stent Restenosis: Associations with Angiographic Stenosis Burden and Mehran Classification
by Mert Deniz Savcilioglu, Kemal Ozan Lule, Osman Buyukcelebi and Ertan Vuruskan
Medicina 2026, 62(7), 1358; https://doi.org/10.3390/medicina62071358 - 14 Jul 2026
Viewed by 233
Abstract
Background and Objectives: Red cell distribution width–standard deviation (RDW-SD) has been associated with systemic inflammation and adverse cardiovascular outcomes, but its relationship with the angiographic severity and morphological complexity of drug-eluting stent-in-stent restenosis (ISR) has not been systematically characterized. The present study [...] Read more.
Background and Objectives: Red cell distribution width–standard deviation (RDW-SD) has been associated with systemic inflammation and adverse cardiovascular outcomes, but its relationship with the angiographic severity and morphological complexity of drug-eluting stent-in-stent restenosis (ISR) has not been systematically characterized. The present study investigated whether RDW-SD is associated with angiographic restenosis severity and restenotic lesion complexity, and compared its performance with the platelet distribution width (PDW), Metabolic Stress Index (MSI), and Platelet-to-HDL Ratio (PHR). Materials and Methods: In this retrospective single-center observational study, 290 patients undergoing clinically indicated repeat coronary angiography following prior drug-eluting stent (DES) implantation were enrolled. Angiographic luminal narrowing was quantified by QCA and categorized as reference (<50% in-stent luminal narrowing; n = 111), intermediate ISR (50–69%; n = 76), and severe ISR (≥70%; n = 103). The Mehran classification was applied to patients with ISR ≥50% and dichotomized as Mehran class I–II (n = 91) vs. Mehran class III–IV (n = 70). Multivariable logistic regression, hierarchical modeling, and incremental discrimination analyses (IDI and NRI) were performed for both binary outcomes. Results: RDW-SD differed significantly across angiographic severity groups (Kruskal–Wallis H = 51.14, p < 0.001), being highest in the ISR ≥70% group [44.6 fL (IQR 43.8–45.3)] and lowest in the ISR 50–69% group [43.2 fL (42.7–43.7)]. A parallel pattern was observed across Mehran class (H = 50.57, p < 0.001; Mehran class III–IV: 44.9 fL [44.2–45.8]). In multivariable analysis, RDW-SD independently associated with ISR ≥70% (OR = 1.228 per 0.5 fL, 95% CI 1.122–1.344, p < 0.001) and Mehran class III–IV (OR = 1.274, 95% CI 1.155–1.406, p < 0.001). Hierarchical modeling showed that adding RDW-SD improved the AUC from 0.603 to 0.719 for ISR ≥ 70% and from 0.592 to 0.757 for Mehran class III–IV (LRT p < 0.001 for both), with incrementally larger IDI and NRI gains for the Mehran class III–IV outcome. PDW did not retain significance after adjustment; MSI and PHR were not significantly associated with either outcome. Conclusions: RDW-SD was independently associated with both angiographic ISR severity and Mehran morphological complexity in patients with established drug-eluting stent restenosis, with numerically greater model discrimination for the Mehran class III–IV endpoint. These findings suggest that RDW-SD may provide complementary information regarding restenosis burden and complexity in patients with established ISR. Prospective studies are required to validate these observations and determine their clinical relevance. Full article
(This article belongs to the Section Cardiology)
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15 pages, 2641 KB  
Article
Integrated Impact of Post-TAVR Cardiac Damage and Pacemaker Implantation on Long-Term Outcomes
by Xinyue Yang, Ruisi Tang, Yijun Yao, Fei Chen, Xingzhou Pu, Xi Wang, Jianyong Wang, Chengqiang Liao, Yun Bao, Chao Li, Yiming Li and Mao Chen
Biomedicines 2026, 14(7), 1569; https://doi.org/10.3390/biomedicines14071569 - 13 Jul 2026
Viewed by 278
Abstract
Background/Objectives: Post-procedural permanent pacemaker implantation (PPMI) and cardiac damage are individually associated with adverse outcomes following transcatheter aortic valve replacement (TAVR). However, their joint impact has not been systematically evaluated. Methods: Individuals who underwent TAVR procedures between 2013 and 2024 were [...] Read more.
Background/Objectives: Post-procedural permanent pacemaker implantation (PPMI) and cardiac damage are individually associated with adverse outcomes following transcatheter aortic valve replacement (TAVR). However, their joint impact has not been systematically evaluated. Methods: Individuals who underwent TAVR procedures between 2013 and 2024 were retrospectively enrolled and classified into four groups based on their PPMI and cardiac damage status. Univariate and multivariable Cox regression were used to analyze the association of these factors with long-term outcomes, while receiver operating characteristic (ROC) curves, decision curve analysis (DCA), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were used to further assess their predictive performance. Results: A total of 1274 patients met the inclusion criteria. Compared to non-PPMI patients with early cardiac damage stage, those with PPMI and advanced stage had higher all-cause mortality (HR: 2.98; 95% CI: 1.60–5.56; p value < 0.001) and more cardiac deaths (HR: 3.85; 95% CI: 1.36–11.10; p = 0.012). Multivariable analysis confirmed PPMI and cardiac damage stage as independent prognostic factors. Notably, the predictive model incorporating both variables achieved the best performance (AUC = 0.703) with significant NRI and favorable DCA results, suggesting incremental value for identifying high-risk patients and acceptable clinical utility. Conclusions: The current study is among the first to explore whether post-procedural cardiac damage may identify a subgroup in whom PPMI carries a particularly adverse long-term prognosis, highlighting the need for integrated risk assessment for post-TAVR lifelong management. Full article
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15 pages, 762 KB  
Article
The Norton Scale at Admission Improves APACHE II-Based Mortality Prediction in the Intensive Care Unit: A Retrospective Cohort Study of 5775 Patients
by Manuel Tejeda-Adell, José Javier de León-Belmar, Marcelino Pérez-Bermejo, Javier Pérez-Murillo, Sonia Gomar-Vidal, Sara Linares-Aguayo, Antonio Alberto Tortosa-Valencia, Ignacio Ventura, Belén Romero-Gómez, Miriam Martínez-Peris, Alma María Palau-Ferré and María Teresa Murillo-Llorente
Medicina 2026, 62(7), 1329; https://doi.org/10.3390/medicina62071329 - 9 Jul 2026
Viewed by 330
Abstract
Background and Objectives: Malnutrition and frailty affect 30–55% of intensive care unit (ICU) patients, yet formal nutritional screening remains inconsistently implemented in routine ICU admission workflows. The APACHE II score, the standard measure of acute physiological severity, does not capture pre-existing nutritional [...] Read more.
Background and Objectives: Malnutrition and frailty affect 30–55% of intensive care unit (ICU) patients, yet formal nutritional screening remains inconsistently implemented in routine ICU admission workflows. The APACHE II score, the standard measure of acute physiological severity, does not capture pre-existing nutritional status or functional reserve. The Norton scale, routinely recorded by nursing staff for pressure-ulcer screening, could serve as a pragmatic proxy for the nutritional-functional axis. We assessed its independent prognostic value at admission for in-hospital and post-ICU mortality. Materials and Methods: Retrospective cohort study of 5775 consecutive adult patients admitted to a Spanish tertiary polyvalent ICU between 2012 and 2019, with APACHE II and Norton scores recorded at admission. The Norton was analysed as continuous and categorised (minimal >14, medium 13–14, high 10–12, very high 5–9). Discrimination was assessed by AUC and DeLong’s test, predictive improvement by IDI and NRI, and internal validity by bootstrap resampling (B = 200). Results: Hospital mortality was 12.8% (n = 738), rising from 7.7% in patients with minimal-risk Norton to 34.5% in very high risk. After adjustment for APACHE II, each additional Norton point reduced the odds of death by 7.7% (adjusted OR = 0.923; 95% CI 0.903–0.943). Adding the Norton to APACHE II improved discrimination (AUC 0.865 → 0.872; DeLong p = 0.003; IDI = 0.011; continuous NRI = 0.30). In the highest APACHE II quartile, the absolute mortality difference between minimal and very high Norton categories reached 23.2 percentage points. The Norton’s prognostic effect was approximately twice as large for post-ICU mortality (ΔAUC +0.011) as for overall in-hospital mortality (ΔAUC +0.006). Conclusions: The Norton scale at admission improves the prognostic capacity of APACHE II in critically ill patients, particularly for post-ICU mortality. Its widespread availability without additional patient-level data collection positions it as a pragmatic candidate for routine prognostic assessment and for guiding targeted nutritional screening. Full article
(This article belongs to the Section Intensive Care/ Anesthesiology)
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11 pages, 1606 KB  
Article
Incremental Predictive Value of the Non-HDL-C/HDL-C Ratio for Cryptogenic Stroke in Patients with Patent Foramen Ovale
by Tarik Yildirim, Mehmet Tolga Hekim and Tuncay Kiris
J. Cardiovasc. Dev. Dis. 2026, 13(7), 313; https://doi.org/10.3390/jcdd13070313 - 8 Jul 2026
Viewed by 272
Abstract
Background: The non-high-density lipoprotein cholesterol (non-HDL-C) / high-density lipoprotein cholesterol (HDL-C) ratio has emerged as a marker of residual vascular risk; however, its role in patent foramen ovale (PFO)-associated cryptogenic stroke (CS) remains unclear. We investigated the association between the non-HDL-C/HDL-C ratio [...] Read more.
Background: The non-high-density lipoprotein cholesterol (non-HDL-C) / high-density lipoprotein cholesterol (HDL-C) ratio has emerged as a marker of residual vascular risk; however, its role in patent foramen ovale (PFO)-associated cryptogenic stroke (CS) remains unclear. We investigated the association between the non-HDL-C/HDL-C ratio and CS in patients with PFO and evaluated its incremental predictive value beyond the Risk of Paradoxical Embolism (ROPE) score. Methods: This retrospective study included 316 patients with confirmed PFO, including 56 patients with CS. Multivariable logistic regression, restricted cubic spline analysis, ROC analysis, net reclassification improvement (NRI), integrated discrimination improvement (IDI), decision curve analysis, and bootstrap internal validation were performed. Results: Patients with CS had significantly higher non-HDL-C/HDL-C ratio levels than those without CS (p < 0.001). In multivariable analysis, the non-HDL-C/HDL-C ratio remained independently associated with CS (OR: 1.881, 95% CI: 1.310–2.700, p < 0.001). Restricted cubic spline analysis demonstrated a significant nonlinear association between the non-HDL-C/HDL-C ratio and CS risk (overall p = 0.001; nonlinear p = 0.015). Addition of the non-HDL-C/HDL-C ratio to the ROPE score improved discrimination, increasing the AUC from 0.781 to 0.819 (DeLong p = 0.010), and significantly improved risk reclassification (continuous NRI: 0.555, p = 0.002; IDI: 0.057, p = 0.002). Internal validation demonstrated stable model performance with minimal optimism. Conclusions: The non-HDL-C/HDL-C ratio was independently associated with CS and demonstrated potential incremental predictive value beyond the ROPE score in patients with PFO. These findings suggest that metabolic lipid burden may contribute to thromboembolic susceptibility and may improve individualized risk stratification in PFO-related stroke. Full article
(This article belongs to the Section Stroke and Cerebrovascular Disease)
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18 pages, 1617 KB  
Article
Comparative Performance of HALP, PNI, and CONUT Scores in No-Reflow Among Patients with Acute Coronary Syndrome: A Prospective Study
by Mert Deniz Savcilioglu, Nil Savcilioglu, Nezihe Otay Lule, Osman Büyükcelebi and Mehmet Murat Sucu
J. Clin. Med. 2026, 15(13), 5191; https://doi.org/10.3390/jcm15135191 - 2 Jul 2026
Viewed by 301
Abstract
Background: Nutritional impairment has been associated with adverse outcomes in acute coronary syndrome (ACS), yet its relationship with the no-reflow phenomenon remains incompletely understood. We aimed to compare the performance of the Hemoglobin–Albumin–Lymphocyte–Platelet (HALP), Prognostic Nutritional Index (PNI), and Controlling Nutritional Status (CONUT) [...] Read more.
Background: Nutritional impairment has been associated with adverse outcomes in acute coronary syndrome (ACS), yet its relationship with the no-reflow phenomenon remains incompletely understood. We aimed to compare the performance of the Hemoglobin–Albumin–Lymphocyte–Platelet (HALP), Prognostic Nutritional Index (PNI), and Controlling Nutritional Status (CONUT) scores for no-reflow assessment in patients with ACS. Methods: This prospective single-centre study included 279 consecutive patients with ACS undergoing percutaneous coronary intervention. HALP, PNI, and CONUT scores were calculated from admission laboratory parameters. No-reflow was defined as post-procedural TIMI flow grade ≤ 2 in the absence of mechanical obstruction, with myocardial blush grade used in equivocal cases. Hierarchical logistic regression, receiver operating characteristic (ROC) analysis, net reclassification improvement (NRI), integrated discrimination improvement (IDI), decision curve analysis, and bootstrap validation were performed. Results: No-reflow occurred in 46 patients (16.5%). All three nutritional indices were significantly associated with no-reflow (all p < 0.001). In multivariable analysis, only the CONUT score remained independently associated with no-reflow (OR 1.728, 95% CI 1.226–2.435, p = 0.002). The addition of nutritional indices to the clinical model improved discrimination, increasing the area under the curve from 0.649 to 0.693 for HALP, 0.733 for PNI, and 0.770 for CONUT. CONUT provided the largest likelihood-ratio improvement (χ2 = 25.98, p < 0.001), NRI (0.757, p < 0.001), and IDI (0.104, p < 0.001). Pairwise DeLong comparisons showed no statistically significant differences among the nutritional models. Internal validation of the CONUT model demonstrated good discrimination and calibration (bootstrap-corrected AUC 0.754). Conclusions: Among the evaluated nutritional indices, CONUT showed the largest incremental improvement in model performance; however, statistically significant superiority over HALP and PNI was not demonstrated. These findings should be considered as exploratory and require confirmation in larger multicentre studies. Full article
(This article belongs to the Section Cardiology)
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11 pages, 1048 KB  
Article
7-Aminopyrazolo[1,5-d][1,2,4]triazin-4(5H)-ones: Synthesis and Growth-Regulating Activity in Chlorella vulgaris
by Ekaterina E. Khramtsova, Anastasia D. Novokshonova, Maksim V. Dmitriev and Pavel V. Khramtsov
Chemistry 2026, 8(7), 90; https://doi.org/10.3390/chemistry8070090 - 1 Jul 2026
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Abstract
A series of 7-aminopyrazolo[1,5-d][1,2,4]triazin-4(5H)-ones was synthesized via a cascade condensation of methyl aroylpyruvates with 1,3-diaminoguanidine hydrochloride. The scope and limitations of this approach were investigated. Methyl mesitoylpyruvate bearing a sterically hindered mesityl substituent diverted the reaction pathway, affording a [...] Read more.
A series of 7-aminopyrazolo[1,5-d][1,2,4]triazin-4(5H)-ones was synthesized via a cascade condensation of methyl aroylpyruvates with 1,3-diaminoguanidine hydrochloride. The scope and limitations of this approach were investigated. Methyl mesitoylpyruvate bearing a sterically hindered mesityl substituent diverted the reaction pathway, affording a 1,2,4-triazine derivative. Diethyl 2,4,6-trioxoheptanedioate resulted in an unexpected pyrazolo[1,5-d][1,2,4]triazepine scaffold. All synthesized compounds were evaluated for growth-regulating activity using the green microalga Chlorella vulgaris as a model organism. 7-Amino-2-(4-methoxyphenyl)pyrazolo[1,5-d][1,2,4]triazin-4(5H)-one has shown the best results in the initial microplate screening, showing increased cell density at 10 μmol/L. However, subsequent validation in 50 mL flask cultures revealed no significant effect on biomass accumulation, photosynthetic pigment content, carbohydrate levels, or neutral lipid production compared to the negative control. Only a modest increase in protein content was observed at the concentration of 100 μmol/L. Full article
(This article belongs to the Section Molecular Organics)
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27 pages, 705 KB  
Article
Knowledge, Attitudes, and Practices of Cattle Farmers Regarding Antibiotic Use and Antimicrobial Resistance in Selected Districts of Zambia
by Doreen Chilolo Sitali, Geoffrey Mainda, Isaac Silwamba, Inyambo Mumbula, Taona Sinyawa, Fusya Yvonne Goma, Steward Mudenda, Mercy Mukuma, Geoffrey Chomba, Niwael Jesse Mtui Malamsha, Suze Percy Filippini and John Bwalya Muma
Antibiotics 2026, 15(7), 651; https://doi.org/10.3390/antibiotics15070651 - 30 Jun 2026
Cited by 1 | Viewed by 288
Abstract
Background: Antimicrobial resistance (AMR) is increasingly recognized as a major public health challenge in Zambia. However, limited evidence exists on the factors driving AMR and antimicrobial use behaviours among cattle farmers. This study explored farmers’ knowledge, attitudes, and practices (KAPs) regarding AMR and [...] Read more.
Background: Antimicrobial resistance (AMR) is increasingly recognized as a major public health challenge in Zambia. However, limited evidence exists on the factors driving AMR and antimicrobial use behaviours among cattle farmers. This study explored farmers’ knowledge, attitudes, and practices (KAPs) regarding AMR and antimicrobial use (AMU), and explored factors influencing them. Methods: Data were collected from Namwala, Mpongwe, and Chingola districts between January and April 2024. A total of 377 cattle farmers participated in a structured survey, supplemented by ten focus group discussions (FGDs) and seventeen in-depth interviews (IDIs). Qualitative data were analysed thematically to identify recurring patterns, while quantitative data were summarized using descriptive statistics and analysed using bivariate tests and regression models to assess key associations. Results: Overall, a small proportion of farmers demonstrated high levels of knowledge (33.9%), positive attitudes (40.4%), and good practices (19.6%) related to AMU and AMR, with significant differences observed across districts. Major drivers of AMU included poor implementation of biosecurity measures, limited access to veterinary services, high reliance on non-prescribed antimicrobials, and weak enforcement of regulations governing antimicrobial distribution. Conclusions: This study highlights critical gaps in AMR-related knowledge and widespread irresponsible AMU among cattle farmers in Zambia. Strengthening targeted AMU/AMR awareness campaigns, improving veterinary service infrastructure, and enhancing regulatory oversight on antibiotic distribution are urgently needed to protect both animal and public health. These findings can support policymakers in designing evidence-based interventions to curb AMR in the livestock sector. Full article
(This article belongs to the Section Antibiotics Use and Antimicrobial Stewardship)
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33 pages, 7388 KB  
Article
Short Interdelivery Interval and Neonatal Acid–Base Status, Postpartum Anemia, and Postnatal Depression: A Retrospective Cohort Study with Within-Mother Sensitivity Analysis
by Ömer Osman Eroğlu, Cansın Eroğlu, Sait Erbey, Mehmet Alican Sapmaz, Murat Polat and Çağanay Soysal
J. Clin. Med. 2026, 15(13), 5053; https://doi.org/10.3390/jcm15135053 - 29 Jun 2026
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Abstract
Background/Objectives: Short interdelivery interval (IDI) is associated with adverse perinatal outcomes, but its relationship with objective neonatal acid–base markers, postpartum anemia, and early postnatal depression remains poorly characterized. We examined IDI < 24 months across four pre-specified outcome domains: neonatal acid–base status, [...] Read more.
Background/Objectives: Short interdelivery interval (IDI) is associated with adverse perinatal outcomes, but its relationship with objective neonatal acid–base markers, postpartum anemia, and early postnatal depression remains poorly characterized. We examined IDI < 24 months across four pre-specified outcome domains: neonatal acid–base status, maternal composite morbidity, postpartum anemia, and early postnatal depression. Methods: This single-center retrospective cohort study included 851 women with two consecutive singleton live births at Ankara Etlik City Hospital between 2023 and 2025. Women were classified by IDI as short (<24 months; n = 635) or standard (≥24 months; n = 216). Multivariable logistic regression provided the primary inference. Sensitivity analyses included inverse probability of treatment weighting (IPTW), restricted cubic splines (4 df), within-mother paired analysis, multiple imputation by chained equations (MICE × 20), Firth penalization, E-values, and Benjamini–Hochberg false discovery rate (FDR) correction across 13 outcomes. Results: After FDR correction, short IDI was associated with postpartum anemia (adjusted odds ratio [aOR] 1.84, 95% confidence interval (CI) 1.26–2.68; q = 0.022) and with an Edinburgh Postnatal Depression Scale score ≥13 (aOR 1.93, 95% CI 1.20–3.10; q = 0.042); umbilical-artery pH < 7.10 did not cross the FDR threshold (aOR 2.37, 1.17–4.82; q = 0.075) and is reported as an exploratory, hypothesis-generating signal. Postpartum anemia did not mediate the IDI–depression association (proportion mediated 0.6%, 95% CI −13.1% to +13.5%). Conclusions: Short IDI was associated with maternal hematologic and psychosocial signals; the IDI–depression link appears non-hematologic. Neonatal acid–base findings did not meet the FDR threshold and are exploratory. Multicenter validation is warranted. Full article
(This article belongs to the Section Obstetrics & Gynecology)
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17 pages, 1697 KB  
Article
Uric Acid-to-Albumin Ratio as a Complementary Biomarker for In-Hospital Risk Stratification in Patients with Pulmonary Hypertension: A Retrospective Cohort Study
by Yuanzheng Ye, He Wang, Yongying Lan, Wenqi Pan, Ning Zhang, Tianyou Ling, Yun Xie, Hongzhen Wang, Qiancheng Ma, Chengze Lin, Baopeng Tang and Liqun Wu
J. Cardiovasc. Dev. Dis. 2026, 13(7), 295; https://doi.org/10.3390/jcdd13070295 - 25 Jun 2026
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Abstract
Background: Oxidative stress is pivotal in pulmonary hypertension. The uric acid-to-albumin ratio (UAR) is a readily available composite biomarker reflecting oxidative stress, inflammation and nutritional status. However, its clinical value for short-term risk stratification in PH remains unclear. Objective: This study [...] Read more.
Background: Oxidative stress is pivotal in pulmonary hypertension. The uric acid-to-albumin ratio (UAR) is a readily available composite biomarker reflecting oxidative stress, inflammation and nutritional status. However, its clinical value for short-term risk stratification in PH remains unclear. Objective: This study aimed to evaluate the association of UAR with in-hospital mortality, clinically recorded PH severity grades, and selected cardiac structural and functional indicators in hospitalized patients with PH. Methods: This single-center retrospective cohort study included 8763 PH patients. Patients were stratified by UAR quartiles. Ordinal logistic regression, multivariable logistic regression, and linear regression were used to assess associations of UAR with clinically recorded PH severity grades, in-hospital mortality, left ventricular ejection fraction (LVEF), and right ventricular internal diameter (RVID). Restricted cubic spline analyses, subgroup analyses, receiver operating characteristic curve analyses, and incremental prediction analyses using C-statistics, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were also performed. Results: In-hospital mortality increased stepwise across UAR quartiles (0.5% vs. 1.0% vs. 1.8% vs. 2.8%, p < 0.001). In the fully adjusted model, each 1-unit increase in UAR was associated with higher odds of a more severe clinically recorded PH grade (OR = 1.11, 95% CI: 1.09–1.13, p < 0.001) and higher odds of in-hospital mortality (OR = 1.09, 95% CI: 1.04–1.14, p < 0.001). Higher UAR was also associated with lower LVEF (β = −0.53, 95% CI: −0.58 to −0.47, p < 0.001) and greater RVID (β = 0.18, 95% CI: 0.15–0.22, p < 0.001). Adding UAR to a model containing routinely available clinical, laboratory, and echocardiographic variables improved the C-statistic from 0.6922 to 0.7230, with significant improvements in NRI and IDI. Conclusions: UAR was independently associated with in-hospital mortality, clinically recorded PH severity, LVEF, and RVID, and provided incremental prognostic information. UAR may serve as a low-cost, routinely available, complementary biomarker for short-term in-hospital risk stratification in patients with PH. Full article
(This article belongs to the Section Cardiovascular Clinical Research)
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