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13 pages, 410 KB  
Article
Predicting Postoperative Mortality in Neonates with Congenital Gastrointestinal Anomalies: Development of a Prognostic Scoring System
by Filla Reviyani Suryaningrat, Eka Rizki Wulandari, Devatri Hudayari, Natasha Amalda Ediwan, Lulu Eva Rakhmilla, Fiva Aprilia Kadi, Aris Primadi and Tetty Yuniati
Children 2025, 12(10), 1313; https://doi.org/10.3390/children12101313 - 30 Sep 2025
Abstract
Background: Congenital gastrointestinal anomalies (CGIAs) are the third most common congenital malformation globally, with a mortality rate reaching 39.8% in developing countries. Surgical intervention is often necessary for life-saving or corrective purposes. However, postoperative mortality in resource-limited settings can reach up to 50%. [...] Read more.
Background: Congenital gastrointestinal anomalies (CGIAs) are the third most common congenital malformation globally, with a mortality rate reaching 39.8% in developing countries. Surgical intervention is often necessary for life-saving or corrective purposes. However, postoperative mortality in resource-limited settings can reach up to 50%. Identifying prognostic factors is essential to improve clinical management and inform family counseling regarding potential outcomes. Objectives: We aimed to develop a prognostic scoring system to predict postoperative mortality in neonates with CGIAs. Methods: This retrospective study analyzed medical records of neonates who underwent surgery for CGIAs between 2020 and 2024. Prognostic factors were identified using logistic regression analysis. Receiver operating characteristic (ROC) curves were used to determine optimal cutoff points for mortality prediction. Results: A total of 282 neonates were included; 121 (42.9%) died and 161 (57.1%) survived. Multivariate logistic regression identified sepsis, mechanical ventilation, prematurity, and upper gastrointestinal anomalies as independent predictors of mortality. A scoring system was developed, with a score > 3 yielding a sensitivity of 83.5% and specificity of 72.0%. The area under the ROC curve (AUC) was 0.840 (p < 0.001). Conclusions: We developed a simple and reliable scoring system to predict postoperative mortality in neonates with CGIAs, which may support clinical decision-making and family counseling. Full article
(This article belongs to the Section Pediatric Neonatology)
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11 pages, 335 KB  
Article
Predictor Role of VKORC1 rs9923231, CYP4F2 rs2108622, and GGCX rs11676382 Polymorphisms of 5 Years Mortality of Patients with Acute Ischemic Stroke
by Silvina Iluţ, Valer Donca, Antonia Eugenia Macarie, Ştefan Cristian Vesa, Raluca Maria Pop, Vitalie Văcăraş, Diana Şipoş-Lascu, Ioana Cristina Bârsan, Lăcrămioara Perju-Dumbravă, Ovidiu Sorin Chiroban, Camelia Alexandra Coadă and Anca Dana Buzoianu
Medicina 2025, 61(10), 1760; https://doi.org/10.3390/medicina61101760 - 28 Sep 2025
Abstract
Background and Objectives: The aim of this study was to evaluate the potential predictive value of VKORC1, CYP4F2, and GGCX polymorphisms, as well as other clinical and demographic factors, for 5-year mortality in patients with acute ischemic stroke (AIS). Materials [...] Read more.
Background and Objectives: The aim of this study was to evaluate the potential predictive value of VKORC1, CYP4F2, and GGCX polymorphisms, as well as other clinical and demographic factors, for 5-year mortality in patients with acute ischemic stroke (AIS). Materials and Methods: The study enrolled 252 patients who were consecutively hospitalized for AIS. Demographic data, comorbidities, and laboratory tests were collected. Genotyping of the VKORC1 rs9923231 (-1639G > A; VKORC1*2), CYP4F2 rs2108622 (1347C > T), and GGCX rs11676382 (12970C > G) polymorphisms was performed. Mortality was noted if it occurred within five years following the 30 days after discharge, using the National Health Insurance House registry. Results: Death was recorded in 71 (28.1%) patients. In multivariate analysis the following variables were independent variables associated with 5-year mortality: age > 72 years (OR 2.83 (95%CI 1.32; 6.08), p = 0.007), a lesion volume > 12.6 mL (OR 4.05 (95%CI 2.05; 7.99), p < 0.001), and an NIHSS score > 7 (OR—2.64 (95%CI 1.31; 5.31), p = 0.006). VKORC1 (-1639G > A) SNP m/m variant was only marginally associated with mortality. Conclusions: In this study which included AIS patients, VKORC1, CYP4F2, and GGCX polymorphisms did not independently predict mortality. The VKORC1 variant was only marginally associated with mortality, but this was attenuated after correction for multiple testing. Advanced age, NIHSS score, and the lesion volume were independent predictors of long-term mortality in AIS patients. Full article
(This article belongs to the Special Issue Stroke: Diagnostic Approaches and Therapies: 2nd Edition)
14 pages, 1804 KB  
Article
Distal Adding-On as a Natural Shoulder Rebalancing Mechanism in Lenke Type 2A AIS with Right Sacral Slanting
by Jae-Hyuk Yang, Jae Min Park, Hyukjune Seong, Chang Ju Hwang and Hyung Rae Lee
J. Clin. Med. 2025, 14(19), 6850; https://doi.org/10.3390/jcm14196850 - 27 Sep 2025
Abstract
Background/Objectives: Distal adding-on (DA) is a common postoperative phenomenon in Lenke type 2A adolescent idiopathic scoliosis (AIS). Postoperative shoulder imbalance (PSI) is a clinically significant issue following AIS correction, as it may lead to aesthetic dissatisfaction, functional impairment, and reduced quality of [...] Read more.
Background/Objectives: Distal adding-on (DA) is a common postoperative phenomenon in Lenke type 2A adolescent idiopathic scoliosis (AIS). Postoperative shoulder imbalance (PSI) is a clinically significant issue following AIS correction, as it may lead to aesthetic dissatisfaction, functional impairment, and reduced quality of life. This study investigated radiographic changes in DA and shoulder balance in Lenke type 2A AIS, particularly focusing on distal wedge angle (DWA) and radiologic shoulder height (RSH) in patients with right sacral slanting (RSS). Methods: We retrospectively analyzed 120 patients with Lenke type 2A AIS who underwent posterior spinal fusion. Patients were grouped by sacral slanting: right (RSS), left (LSS), or none (NS). Radiographic parameters including proximal thoracic curve angle, main thoracic curve angle, DWA, RSH were assessed at multiple time points. Univariate and multivariate linear regression analyses were used to identify factors associated with DA. Results: The RSS group consistently showed the highest DWA and the greatest incidence of DA. RSH initially exceeded the PSI threshold in all groups but decreased to approximately 10 mm by final follow-up. In the RSS group, the inverse relationship between increasing DWA and decreasing RSH was most pronounced. Univariate regression identified postoperative RSH and sacral slanting angle as significant predictors of DWA, though not in the final multivariate model. Conclusions: In Lenke type 2A AIS with RSS, an increasing DWA and decreasing RSH over time suggest that DA may serve as a compensatory mechanism for PSI. Sacral slanting and postoperative RSH may be relevant predictors of this dynamic alignment change. Full article
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11 pages, 467 KB  
Article
Impact of a Failsafe Reminder Letter and Associated Factors on Correct Follow-Up After a Positive FIT in the Flemish Colorectal Cancer Screening Program
by Sarah Hoeck and Thuy Ngan Tran
Gastrointest. Disord. 2025, 7(4), 61; https://doi.org/10.3390/gidisord7040061 - 26 Sep 2025
Abstract
Background: Timely diagnostic colonoscopy (DC) after a positive fecal immunochemical test (FIT+) is essential for effective colorectal cancer (CRC) screening. In Flanders, 16% of FIT+ participants in 2022 had no DC in the 24 months following the FIT+ result. This study evaluated the [...] Read more.
Background: Timely diagnostic colonoscopy (DC) after a positive fecal immunochemical test (FIT+) is essential for effective colorectal cancer (CRC) screening. In Flanders, 16% of FIT+ participants in 2022 had no DC in the 24 months following the FIT+ result. This study evaluated the impact of a failsafe reminder letter—sent 24 months after a FIT+ result without registered correct follow-up—on DC completion and identified factors associated with correct follow-up. Methods: We included all individuals in the Flemish CRC screening program who had a FIT+ result between 2017 and 2019 and later received a failsafe letter due to lacking correct follow-up within 24 months. Correct follow-up was defined as a complete colonoscopy, virtual colonoscopy, or cancer diagnosis. We calculated the proportion of individuals completing correct follow-up within 24 months of the letter. Multivariable logistic regression examined associations between odds of correct follow-up and individual and area-level characteristics. Results: Of the 7175 individuals who received a failsafe letter, 16.1% completed correct follow-up within 24 months. Individuals aged 70–74 had significantly lower odds of correct follow-up than those aged 60–64 (odd ratio (OR) = 0.59; 95% confidence interval (CI): 0.48–0.72). Living in areas with a higher proportion of young adults in higher education was associated with higher odds of correct follow-up (OR = 1.041; 95% CI: 1.002–1.080). Conclusions: The failsafe letter modestly improved follow-up among a hard-to-reach group. Older age and lower area-level educational attainment were linked to reduced odds of correct follow-up. Targeted efforts are needed to improve DC completion in these subgroups. Full article
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17 pages, 1273 KB  
Article
Clinical and Histopathological Correlates of Endometrial Proliferative Lesions in Perimenopausal Women: A Retrospective Study with Internal Validation of a Risk Model
by Anca Daniela Brăila, Viorica Tudor, Cristian-Viorel Poalelungi, Constantin Marian Damian, Claudia Florina Bogdan-Andreescu, Alexandru Burcea, Andreea-Mariana Bănățeanu, Emin Cadar and Cristina-Crenguţa Albu
Clin. Pract. 2025, 15(10), 177; https://doi.org/10.3390/clinpract15100177 - 26 Sep 2025
Abstract
Background: Endometrial proliferative lesions are common in the menopausal transition and carry a measurable risk of carcinoma. Early risk stratification may guide evaluation and follow-up. Methods: We performed a single-center retrospective study of 315 women aged 45–55 years (May 2021–May 2024) at a [...] Read more.
Background: Endometrial proliferative lesions are common in the menopausal transition and carry a measurable risk of carcinoma. Early risk stratification may guide evaluation and follow-up. Methods: We performed a single-center retrospective study of 315 women aged 45–55 years (May 2021–May 2024) at a private clinic in Bucharest. Lesions were classified per WHO 2014 as hyperplasia without atypia, atypical hyperplasia/endometrial intraepithelial neoplasia (AH/EIN), or adenocarcinoma; “advanced pathology” was defined as AH/EIN or adenocarcinoma. Clinical comorbidities and transvaginal ultrasound endometrial thickness were recorded. Associations were tested with χ2; odds were estimated with multivariable logistic regression (adjusted ORs), with a modified Poisson sensitivity analysis for adjusted relative risk. Thickness differences were compared by one-way ANOVA, and severity correlations by Spearman’s ρ. Internal validation used 1000-bootstrap resampling. Results: Hyperplasia without atypia comprised 74.6% of cases, AH/EIN 20.0%, and adenocarcinoma 5.4% (advanced pathology 25.4%). Diabetes was independently associated with advanced pathology (aOR 2.75; 95% CI 1.14–6.61; p = 0.0237), while a history of non-atypical hyperplasia was inversely associated (aOR 0.31; 95% CI 0.13–0.72; p = 0.0068). Obesity showed a borderline association (aOR 1.79; 95% CI 0.98–3.26; p = 0.058), and long-term oral contraceptive use also approached significance (aOR 0.42; 95% CI 0.18–1.00; p = 0.051). Endometrial thickness increased stepwise with histopathological severity (ANOVA p < 0.0001; η2 = 0.44) and correlated with ordered severity (ρ = 0.634). The multivariable model showed moderate discrimination (AUC 0.68; optimism-corrected 0.66) with acceptable calibration (slope 0.92; Hosmer–Lemeshow p = 0.052) and overall accuracy (Brier 0.18). Conclusions: In perimenopausal abnormal bleeding, metabolic comorbidities—especially diabetes—together with increased endometrial thickness identify women at higher risk of AH/EIN or carcinoma. Histopathology remains the diagnostic reference. The model can aid clinical prioritization but requires external validation and should not be used as the sole basis for decisions. Full article
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14 pages, 273 KB  
Study Protocol
Protocol for a Prospective Cohort Study on Determinants of Outcomes in Lumbar Radiculopathy Surgery
by Alejandro Aceituno-Rodríguez, Carlos Bustamante, Carmen Rodríguez-Rivera, Miguel Molina-Álvarez, Carlos Rodríguez-Moro, Rafael García-Cañas, Carlos Goicoechea and Luis Matesanz-García
Healthcare 2025, 13(19), 2444; https://doi.org/10.3390/healthcare13192444 - 26 Sep 2025
Abstract
Introduction: Lumbar radiculopathies involving the entrapment of nerve roots in the lumbar spine are common neuropathic conditions. These conditions affect 40% to 70% of individuals in their lifetime and lead to significant medical costs. Objective: This study aims to identify clinical, psychological, [...] Read more.
Introduction: Lumbar radiculopathies involving the entrapment of nerve roots in the lumbar spine are common neuropathic conditions. These conditions affect 40% to 70% of individuals in their lifetime and lead to significant medical costs. Objective: This study aims to identify clinical, psychological, and biomarker-based prognostic factors that predict functional outcomes following surgery for lumbar radiculopathy. Materials and Methods: This prospective cohort study, conducted at Hospital Central de la Defensa Gómez Ulla, Madrid (Spain), adheres to the STROBE guidelines. The study includes patients aged 18–75 with lumbar radiculopathy, confirmed by clinical diagnosis, imaging, and electromyography (EMG) findings. Exclusion criteria include previous lumbar spine surgeries and systemic diseases. The primary outcome is the Oswestry Low Back Pain Disability Questionnaire. Sample size calculations, based on a conservative effect size (f2 = 0.20), determined the need for 172 participants, accounting for a 15% dropout rate and 80% power. Procedure: Patients will undergo an initial assessment, including EMG tests, sociodemographic and psychological questionnaires, blood sample tests, and physical questionnaires. This process will be repeated six months post-intervention, except for the blood sample test, expectations questionnaire, and EMG, which will be performed only once. Statistical Analyses: Data will be analyzed using Python 3.12.3, employing a multivariate linear regression analysis. Assumptions of linearity, independence, homoscedasticity, normality, and no multicollinearity will be validated. Corrective measures will be applied if assumptions are violated. Ethics and Dissemination: The study follows the Declaration of Helsinki guidelines and has been approved by the Ethics Committee of Universidad Rey Juan Carlos (070220241052024). Potential risks will be minimized, and adverse events will be recorded and addressed. Findings will be published in high-impact journals and presented at conferences. Full article
17 pages, 384 KB  
Article
Validating a Revised Oral Frailty 5-Item Checklist (OF-5) to Detect Pre-Symptomatic Brain Changes in Cognitively Unimpaired Older Adults
by Makoto Murahashi, Kenjiro Ono, Moeko Noguchi-Shinohara, Mai Ishimiya-Jokaji, Kentaro Ide, Toshihiro Kawano, Shusuke Tokuchi, Risako Suzuki, Mikana Isa, Shuichi Kawashiri and Hiroyuki Nakamura
Nutrients 2025, 17(19), 3058; https://doi.org/10.3390/nu17193058 - 25 Sep 2025
Abstract
Objective: Oral frailty is associated with an increased risk of cognitive decline, yet practical tools for early identification remain limited. The Oral Frailty 5-item Checklist (OF-5), recently standardized in Japan, does not account for severe tooth loss, which is a known risk factor [...] Read more.
Objective: Oral frailty is associated with an increased risk of cognitive decline, yet practical tools for early identification remain limited. The Oral Frailty 5-item Checklist (OF-5), recently standardized in Japan, does not account for severe tooth loss, which is a known risk factor for brain atrophy. We developed a revised version of the OF-5 that includes the criterion of having nine or fewer teeth. This study aimed to validate the revised OF-5 as a screening tool for detecting early brain structural changes related to dementia risk in cognitively unimpaired older adults. Methods: We analyzed 732 cognitively unimpaired participants from a population-based Japanese cohort (baseline 2016–2018). Oral frailty was assessed using both the original OF-5 and the revised OF-5. Brain volumes were measured by MRI and processed with FreeSurfer. Associations between oral frailty status and regional brain volumes were tested using multivariable-adjusted models, with further adjustment for nutrient intake and food consumption. Results: The revised OF-5, which adds severe tooth loss (≥9 teeth) as a criterion, showed greater sensitivity in detecting dementia-related brain changes than the original version. With the original OF-5, oral frailty was associated only with reduced fusiform gyrus volume (1.088% vs. 1.109% of estimated total intracranial volume [eTIV]; p < 0.05). In contrast, the revised OF-5 detected broader changes: orally frail participants showed significantly higher white matter hyperintensity (WMH) volume (0.366% vs. 0.302% of eTIV; p < 0.05) and smaller volumes in the medial temporal lobe (1.824% vs. 1.856%), pars triangularis (0.401% vs. 0.412%), and fusiform gyrus (1.080% vs. 1.111%)—all p < 0.05 (FWE-corrected). These associations persisted after adjusting for nutrient intake and food consumption. Conclusions: The revised OF-5 improves identification of pre-symptomatic brain changes in cognitively healthy older adults, independent of nutrition. It may serve as a simple and practical tool for early screening of dementia risk in clinical and community settings. Full article
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13 pages, 606 KB  
Article
Inflammatory Profile and Risk of Hypertension in Infants Following Coarctation of the Aorta Repair: The Role of IL-6/TNF-α Ratio
by Irina-Maria Margarint, Vlad Anton Iliescu, Tammam Youssef, Iulian Rotaru, Alexandru Popescu, Olguta Untaru and Radu Vladareanu
Life 2025, 15(9), 1481; https://doi.org/10.3390/life15091481 - 21 Sep 2025
Viewed by 159
Abstract
Background: Despite anatomically successful surgical correction, postoperative hypertension remains a significant concern in patients with coarctation of the aorta, even when repair is performed during infancy. Inflammation and neurohormonal activation have been proposed as contributing mechanisms. Objective: To investigate the association between preoperative [...] Read more.
Background: Despite anatomically successful surgical correction, postoperative hypertension remains a significant concern in patients with coarctation of the aorta, even when repair is performed during infancy. Inflammation and neurohormonal activation have been proposed as contributing mechanisms. Objective: To investigate the association between preoperative inflammatory biomarkers—specifically the interleukin-6 (IL-6) to tumor necrosis factor-alpha (TNF-α) ratio—and the development of hypertension in patients with successful isolated coarctation of the aorta repair under one year of age. Methods: This observational study included 42 infants with isolated CoA. Clinical, echocardiographic, and biochemical parameters were analyzed. Preoperative plasma levels of IL-6, TNF-α, von Willebrand factor (vWF), and renin were measured. Patients were classified based on hypertensive status at 2-year follow-up. Univariate and multivariate logistic regression analyses were performed to identify predictors of postoperative hypertension. Results: Hypertension was diagnosed in 16 out of 41 patients (39%) at follow-up. A preoperative IL-6/TNF-α ratio > 2 was an independent predictor in multivariate analysis for postoperative HT (OR = 6.1, 95% CI = 6.23–9.31, p = 0.02). Conclusions: In this small single-center cohort, an elevated IL-6/TNF-α ratio was associated with postoperative hypertension after coarctation repair. These exploratory findings should be considered hypothesis-generating and warrant confirmation in larger, multicenter studies. Full article
(This article belongs to the Section Medical Research)
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10 pages, 564 KB  
Article
Gender Differences in Weight Loss Extent Following Bariatric Surgery
by Santo Colosimo, Federica Sileo, Andrea Gambetti, Francesco Frattini, Amalia Bruno, Sara Mambrini, Luisa Gilardini, Federica Barbera, Alice Gotti, Verdiana Vincenti, Laura Inì, Margherita Novelli, Raffaella Cancello, Gianlorenzo Dionigi and Simona Bertoli
J. Clin. Med. 2025, 14(18), 6605; https://doi.org/10.3390/jcm14186605 - 19 Sep 2025
Viewed by 223
Abstract
Background/Objectives: Metabolic–bariatric surgery (MBS) is a highly effective treatment for severe obesity; however, gender disparities exist in access and postoperative outcomes. Despite men presenting with higher baseline weight and comorbidity burden, they are significantly underrepresented among MBS patients. Existing evidence on gender-specific outcomes [...] Read more.
Background/Objectives: Metabolic–bariatric surgery (MBS) is a highly effective treatment for severe obesity; however, gender disparities exist in access and postoperative outcomes. Despite men presenting with higher baseline weight and comorbidity burden, they are significantly underrepresented among MBS patients. Existing evidence on gender-specific outcomes remains inconclusive, particularly within Mediterranean populations under updated clinical guidelines. To evaluate gender differences in weight loss outcomes following sleeve gastrectomy in an Italian cohort managed under current multidisciplinary protocols. Methods: A prospective observational study was conducted and a total of 131 patients (109 females, 22 males) underwent sleeve gastrectomy at a single center. Anthropometric and metabolic parameters were assessed at baseline and 12 months postoperatively. Outcomes included absolute weight loss (TWL%), percentage of initial and excess body weight lost (EWL%), and waist circumference. Group comparisons used t-tests (with Welch’s correction if variances were unequal) and regression models adjusted for baseline BMI and age. Results: At 12 months, men achieved significantly greater absolute weight loss than women (−36.6 kg vs. −31.2 kg; p = 0.028), although no significant differences were observed for TWL%, EWL%, or waist circumference reduction. Gender remained a significant predictor of absolute weight loss in multivariate analysis, but not of proportional weight loss. Both genders showed similar rates of achieving clinically significant weight loss thresholds. Conclusions: While men exhibited greater absolute weight loss, relative weight loss outcomes were comparable between sexes. Gender disparity is observed in the utilization of MBS. These findings highlight the importance of equitable surgical access and tailored postoperative care. Full article
(This article belongs to the Special Issue Clinical Advances in Obesity and Bariatric Surgery—2nd Edition)
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14 pages, 759 KB  
Article
The Relationship Between Preoperative Serum Ionized Calcium, Vitamin D, and Postoperative Bleeding After Major Cardiac Surgery
by Adrian Stef, Constantin Bodolea, Aurelia Georgeta Solomonean, Nadina Tintiuc, Alexandru Oprea, Oana Antal, Gabriel Cismaru and Emanuel Palade
Life 2025, 15(9), 1460; https://doi.org/10.3390/life15091460 - 17 Sep 2025
Viewed by 205
Abstract
Objective: The role of calcium in coagulation homeostasis is well established, although the relationship between calcium levels and postoperative bleeding in major cardiac surgery remains largely unexplored. Methods: This retrospective, single-center study investigated the correlations between ionized calcium levels measured at several timepoints: [...] Read more.
Objective: The role of calcium in coagulation homeostasis is well established, although the relationship between calcium levels and postoperative bleeding in major cardiac surgery remains largely unexplored. Methods: This retrospective, single-center study investigated the correlations between ionized calcium levels measured at several timepoints: preoperatively (after induction of anesthesia), immediately after cardiopulmonary bypass (CPB) weaning, on the first postoperative day measured three times at 8 h intervals, preoperative vitamin D values, and several significant bleeding outcomes. These outcomes included the volume of blood in the drainage bag (measured in milliliters on days 1 and 2), the need for surgical or medical hemostasis, the requirement for blood transfusion (red blood cells, fresh frozen plasma, or platelets), and the occurrence of extracardiac hemorrhagic complications. A multivariable logistic regression analysis was performed, with a two-sided p-value of <0.00625 considered significant after applying Bonferroni correction. Results: The study included 83 patients with a mean age of 64.9 ± 8.5 years, with 49 (59%) being male. The most common procedures were aortic valve replacement (26 patients, 31%) and coronary artery bypass grafting (26 patients, 31%). The multivariable regression analysis demonstrated a trend toward an association between low levels of preoperative calcium and increased bleeding volume immediately after CBP and on the first day after the intervention (r = 0.30; p = 0.08 for day 1 and r = 0.24; p = 0.03 for day 2). Similar trends were observed for the association between low levels of preoperative calcium, use of medical hemostasis (r = 0.30; p = 0.009), and red blood cell transfusion (r = 0.24; p = 0.03). Additionally, we observed a trend towards a positive correlation between lower serum vitamin D levels and increased postoperative blood loss on both day 1 (r = 0.32; p = 0.07) and day 2 (r = 0.29; p = 0.04). The subgroup analysis of valve procedures vs. coronary procedures showed no statistically difference between preoperative ionized calcium levels, postoperative bleeding (289 27 vs. 283 mL, p = 0.87), the need for surgical hemostasis (p = 0.5), or blood transfusion requirement (p = 0.57). Conclusions: In our study, preoperative calcium levels were consistently associated with increased bleeding after major cardiac surgery. Post-CPB ionized calcium levels did not influence bleeding outcomes. The role of calcium in coagulation homeostasis during major cardiac surgery warrants further research, ideally with more robust data, as our study’s small sample limits robust evidence. Further larger studies will conclude on the importance of calcium levels in cardiac surgery related to hemostasis and bleeding outcomes. Lower preoperative ionized calcium and vitamin D levels showed exploratory associations with increased bleeding-related outcomes following major cardiac surgery. These findings are hypothesis-generating, and larger prospective studies are needed to confirm these potential relationships and clarify their clinical implications. Full article
(This article belongs to the Special Issue Critical Issues in Intensive Care Medicine)
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19 pages, 2541 KB  
Article
A Comparative Bioinformatic Analysis of Optic Nerve Axon Regeneration Lipidomes Using the Xenopus laevis as a Model System
by Vernon S. Volante, Fiona L. Watson and Sanjoy K. Bhattacharya
Methods Protoc. 2025, 8(5), 110; https://doi.org/10.3390/mps8050110 - 15 Sep 2025
Viewed by 329
Abstract
Lipidomics is a rapidly growing branch of metabolomics that identifies lipid compositions of samples to learn more about disease and identify potential novel therapeutic targets. In the context of ophthalmology, lipidomic research has increased our understanding of optic nerve regeneration. The diversity of [...] Read more.
Lipidomics is a rapidly growing branch of metabolomics that identifies lipid compositions of samples to learn more about disease and identify potential novel therapeutic targets. In the context of ophthalmology, lipidomic research has increased our understanding of optic nerve regeneration. The diversity of experimental designs for lipidomic research and the large datasets generated are two obstacles that must be addressed by bioinformatic tools to perform statistical analysis on lipidomics data. Our study provides an objective comparison of the features in two freely accessible web-based bioinformatics tools, MetaboAnalyst 6.0 and LipidOne 2.3, for analyzing an optic nerve regeneration model lipidome. A publicly available lipidomic dataset of the optic nerve axon regeneration model, Xenopus laevis, was used to compare the analytic capabilities of both tools. Though both tools offered univariate and multivariate analysis methods, MetaboAnalyst 6.0 had advantages in customizable data processing, normalization, analysis, and image generation. It also offered consistent multiple-comparison testing correction and comprehensive results/dataset export. Meanwhile LipidOne 2.3 uniquely allowed for univariate and multivariate analysis of lipid classes and lipid building blocks. Full article
(This article belongs to the Section Molecular and Cellular Biology)
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16 pages, 1942 KB  
Article
Fecal Metabolomics for the Diagnosis of Clostridioides difficile Infection
by Carlos Bea-Serrano, Andreu Belmonte-Domingo, Carolina Pinto-Pla, Ana Ferrer-Ribera, Sara Vela-Bernal, Ana Isabel de Gracia-León, Andrea de Castro-Oliver, Lucas Serna-Navarro, Celia Prades-Sirvent, David Ruiz-Raga, María José Galindo, María José Forner-Giner and María Rosa Oltra-Sempere
Diagnostics 2025, 15(18), 2331; https://doi.org/10.3390/diagnostics15182331 - 15 Sep 2025
Viewed by 295
Abstract
Background: Clostridioides difficile infection (CDI) is the leading cause of nosocomial diarrhea. Current diagnostic tools have difficulty distinguishing between colonization and active infection. This study evaluated the utility of fecal metabolomics in diagnosing CDI in hospitalized patients with acute diarrhea. Methods: [...] Read more.
Background: Clostridioides difficile infection (CDI) is the leading cause of nosocomial diarrhea. Current diagnostic tools have difficulty distinguishing between colonization and active infection. This study evaluated the utility of fecal metabolomics in diagnosing CDI in hospitalized patients with acute diarrhea. Methods: We conducted a prospective observational study involving hospitalized adults with new-onset diarrhea during admission. Participants were stratified into groups based on clinical and microbiological findings: controls, C. difficile colonized and C. difficile infected. Fecal samples were analyzed using UPLC-MS/MS and GC-MS to quantify selected short-chain fatty acids, amino acids, and bile acids. Multivariate and univariate statistical analyses included PLS-DA, sPLSDA, and tests with FDR correction. Results: Infected patients exhibited significantly higher concentrations of SCFAs and notable alterations in bile acid profiles. Key discriminative metabolites included isovalerate, propionate, isobutyrate and alpha-aminobutyric acid. ROC curve analyses showed strong diagnostic performance for these markers, with AUC values exceeding 0.85. Conclusions: Fecal metabolomic profiling could effectively differentiate between colonization and infection in CDI among hospitalized patients with diarrhea. These results highlight the potential of metabolomic signatures to enhance the diagnostic precision for CDI. Full article
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14 pages, 1609 KB  
Article
A Deep Learning Framework for Classification of Neuroendocrine Neoplasm Whole Slide Images
by Amir Hadjifaradji, Michael Diaz-Stewart, Jenny Chu, David Farnell, David Schaeffer, Hossein Farahani, Ali Bashashati and Jonathan M. Loree
Cancers 2025, 17(18), 2991; https://doi.org/10.3390/cancers17182991 - 13 Sep 2025
Viewed by 342
Abstract
Background/Objectives: Neuroendocrine neoplasms (NENs) are uncommon neoplasms. Grading informs the prognosis and treatment decision of NENs and is determined by cell proliferation, which is measured by mitotic count and Ki-67 index. These measurements present challenges for pathologists as they suffer inter- and [...] Read more.
Background/Objectives: Neuroendocrine neoplasms (NENs) are uncommon neoplasms. Grading informs the prognosis and treatment decision of NENs and is determined by cell proliferation, which is measured by mitotic count and Ki-67 index. These measurements present challenges for pathologists as they suffer inter- and intra-observer variability and are cumbersome to quantify. To address these challenges, we developed a machine learning pipeline for identifying tumor areas, proliferating cells, and grading NENs. Methods: Our study includes 385 samples of gastroenteropancreatic NENs from across British Columbia with two stains (247 H&E and 138 Ki-67 images). Labels for these cases are at the patient-level, and there are 186 patients. We systematically investigated three settings for our study: H&E, H&E with Ki-67, and pathologist-reviewed and corrected cases. Results: Our H&E framework achieved a three-fold balanced accuracy of 77.5% in NEN grading. The H&E with Ki-67 framework yields a performance improvement to 83.0% on grading. We provide survival and multivariate analysis with a c-index of 0.65. Grade 1 NENs misclassified by the model were reviewed by a pathologist to assess reasons. Analysis of our AI-graded NENs for the subset of pathologist-assessed G1s demonstrated a significant (p-value = 0.007) survival difference amongst samples the algorithm assigned to a higher grade (n = 20; median survival 4.22 years) compared to concordant G1 samples (n = 60; median survival 10.13 years). Conclusions: Our model identifies NEN grades with high accuracy and identified some grade 1 tumors as prognostically unique, suggesting potential improvements to standard grading. Further studies are needed to determine if this discordant group is a different clinical entity. Full article
(This article belongs to the Special Issue AI-Based Applications in Cancers)
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13 pages, 2042 KB  
Article
CDCA8 and TROAP as Prognostic Biomarkers of Postoperative Metastatic Progression in Clear Cell Renal Cell Carcinoma
by Mingyu Kim, Geehyun Song, Jaeyoung Joung, Hokyung Seo, Hyungho Lee and Jinsoo Chung
Cancers 2025, 17(18), 2975; https://doi.org/10.3390/cancers17182975 - 11 Sep 2025
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Abstract
Objectives: Clear cell renal cell carcinoma (ccRCC) may later metastasize despite curative surgery. This study asked whether transcriptomic alterations detectable at nephrectomy are associated with subsequent metastatic progression, and whether such signals retain prognostic relevance in overt metastatic disease. Methods: Bulk RNA sequencing [...] Read more.
Objectives: Clear cell renal cell carcinoma (ccRCC) may later metastasize despite curative surgery. This study asked whether transcriptomic alterations detectable at nephrectomy are associated with subsequent metastatic progression, and whether such signals retain prognostic relevance in overt metastatic disease. Methods: Bulk RNA sequencing was performed in 30 ccRCC patients without metastasis at surgery; 4 developed distant metastasis during follow-up. Differential expression, enrichment, and network analyses identified hub genes, which were screened by ROC analysis with bootstrap optimism correction. External validation used TCGA-KIRC focusing on patients metastatic at baseline (M1) to evaluate overall and disease-specific survival with multivariable Cox models (per-SD expression, adjusted for age, sex, and stage); Kaplan–Meier curves were shown for visualization only. Results: Fifty-nine DEGs distinguished patients who later metastasized from those who remained metastasis-free, with enrichment in mitotic and chromosomal-segregation pathways. Five hub genes (BASP1, CDCA8, KIF2C, LMNB1, TROAP) showed high discrimination in the discovery set (optimism-corrected AUC ~0.92–0.93). In TCGA-M1, CDCA8, and TROAP were consistently associated with worse survival and remained significant in multivariable models. Conclusions: Dysregulation of mitotic control may underlie latent metastatic competence in ccRCC. CDCA8 and TROAP emerge as candidate prognostic biomarkers, linking postoperative metastatic progression in an initially M0 cohort with survival in metastatic disease. These hypothesis-generating findings warrant validation in larger, prospective cohorts. Full article
(This article belongs to the Special Issue Genitourinary Malignancies)
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14 pages, 624 KB  
Article
Socio-Demographic Factors Linked to Psychological Well-Being in Dementia Caregivers
by Liviu Florian Tatomirescu, Cristiana Susana Glavce, Gabriel Ioan Prada, Adriana Borosanu and Suzana Turcu
Healthcare 2025, 13(17), 2235; https://doi.org/10.3390/healthcare13172235 - 7 Sep 2025
Viewed by 484
Abstract
Background: Caregivers of individuals with cognitive impairment face heightened emotional and psychological burdens, yet the interaction between caregiver well-being, patient characteristics, and socio-demographic factors still requires investigation. This study aimed to examine the psychological well-being of family caregivers in an urban Romanian context, [...] Read more.
Background: Caregivers of individuals with cognitive impairment face heightened emotional and psychological burdens, yet the interaction between caregiver well-being, patient characteristics, and socio-demographic factors still requires investigation. This study aimed to examine the psychological well-being of family caregivers in an urban Romanian context, focusing on the role of depressive and anxiety symptoms, education, and care-recipient cognition function. Methods: A cross-sectional study was conducted among family caregivers recruited from a neurology-psychiatry service in Bucharest. Caregivers completed Ryff’s Psychological Well-Being Scales, the Patient Health Questionnaire-9 (PHQ-9), and the COVI Scale. Cognitive status of care recipients was obtained from medical records (Mini-Mental State Examination, MMSE). Descriptive statistics, correlation analyses, and separate linear regression models were performed for each well-being dimension. Results: Caregivers reported moderate to high well-being scores, with Environmental Mastery highest (M = 38.01, SD = 8.70) and Purpose in Life lowest (M = 33.14, SD = 6.72). Depression scores averaged 18.49 (SD = 6.55), indicating moderate depressive symptoms, and anxiety scores averaged 12.14 (SD = 2.23), consistent with severe anxiety. Cognitive impairment in care recipients was marked (MMSE M = 11.47, SD = 6.99). Bivariate analyses showed that lower MMSE scores were associated with higher caregiver anxiety (ρ = −0.287, p = 0.014). Regression models (R2 = 0.08–0.25) indicated that higher education was positively associated with autonomy, personal growth, positive relations, and environmental mastery, whereas older age and female gender were linked to lower well-being in several domains. Depressive symptoms were unexpectedly associated with higher autonomy and self-acceptance. Conclusions: Caregiver psychological well-being was modestly associated with depressive symptoms, education, gender, and age, while care-recipient cognitive status showed only weak links to anxiety. Education emerged as a consistent protective factor, whereas female gender and older age were associated with lower well-being. Although the Bonferroni correction eliminated significance in separate models, a complementary multivariate multiple regression confirmed global effects of education, caregiver gender, and depression across well-being domains. These findings emphasize the need for systematic psychological support for caregivers and call for larger, longitudinal studies to clarify causal mechanisms and additional protective factors. Full article
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