Optimizing oncological outcomes in high-grade non-muscle invasive bladder cancer: The impact of a surgeon-led treatment pathway.

Obesity and T2DM substantially increase postoperative risk, with higher surgical site infections in obesity and up to a 65% increase in overall complications in T2DM. This study assesses the impact of weight loss interventions-metabolic bariatric surgery (MBS) and glucagon-like peptide-1 receptor agonists (GLP-1RA)-on BMI reduction and how that translates to postoperative outcomes in general surgery patients. Patients undergoing general surgery (2016-2024) were identified in the Epic Cosmos database. GLP-1RA or MBS exposure occurred 1-3 years preoperatively (GLP-1RA coverage ≥ 80%). Entropy balancing produced weighted cohorts with similar baseline profiles, followed by multivariable regression models assessing the association between weight loss intervention and BMI change, and the impact of BMI on postoperative outcomes. Overall 9470 individuals underwent a general surgery procedure. Median patient age was 64, with mostly females (60.6%). More patients received GLP-1RA (n = 7823, 82.3%) than MBS (n = 1647, 17.4%). MBS patients had higher initial BMIs (≥ 40: 60.8% vs. 24.5%, p < 0.001). MBS led to greater BMI reduction than GLP-1RA (Mean difference: -9.89, 95% CI: -9.64, -10.34). Higher BMI at time of a general surgical procedure correlated with increased postoperative complications (OR: 1.01, 95% CI: 1.00-1.01) and extended LOS (OR: 1.01, 95% CI: 1.00-1.01). MBS was associated with lower complication odds (OR: 0.87, 95% CI: 0.78-0.98). MBS improved surgical outcomes in patients with obesity and T2DM through greater BMI reduction compared with GLP-1RAs. These findings support the role of preoperative weight loss to mitigate surgical risk; however, evaluating outcomes relative to no intervention remains an important future direction.

Early identification of patients with suspected infection who are at risk of clinical deterioration in the Emergency Department (ED) is challenging, yet crucial for timely initiation of appropriate care and prevention of clinical deterioration. This multicenter international study evaluates the performance of established scores (SIRS, LODS, qSOFA, SOFA, NEWS) in predicting severe outcomes in ED patients with suspected infection. We combined data from five different ED cohort studies (n = 4044 adult patients) from the Netherlands and Sweden. Suspected infection was defined as obtaining a microbiological culture combined with starting antibiotics. The scores were evaluated for their accuracy in predicting the composite outcome of intensive care unit (ICU) admission and in-hospital mortality. Of 4044 patients, 655 (16 %) experienced a severe outcome, defined as ICU admission (n = 429, 11 %) or in-hospital mortality (n = 327, 8 %). SOFA (AUC 0.75 [95 %CI:0.73-0.77]) and LODS (AUC 0.73 [95 %CI:0.71-0.75]) showed the highest predictive accuracy. NEWS ≥ 5 yielded fair sensitivity (78 %) but low specificity (40 %), whereas NEWS ≥ 7 (sensitivity 71 %, specificity 59 %) performed similarly to SOFA ≥ 2 (69 %, 68 %) and LODS ≥ 2 (70 %, 66 %). In contrast, qSOFA (AUC 0.66 [95 %CI:0.64-0.69]) and SIRS (AUC 0.54 [95 %CI:0.52-0.57]) performed poorly for ED risk stratification. SOFA and LODS showed the highest accuracy but are limited by their complexity and the requirement for laboratory data. The NEWS score, simpler and more accessible, is a practical tool for rapid ED screening with comparable accuracy as SOFA and LODS.

Burns patients with recorded discharges against medical advice (DAMA) face potential medical and financial consequences associated with future readmissions. This study aimed to investigate the characteristics and outcomes of patients with recorded DAMA from burns services in Australia and New Zealand. In an observational study using data from individuals aged ≥ 16 years captured by the Burns Registry of Australia and New Zealand with a burn-related admission between July 2009 and June 2022, 325 patients (1.4 %) had recorded DAMA. A greater proportion of patients with recorded DAMA were aged 30-44 years, of Australian Aboriginal and Torres Strait Islander origin, from outer regional Australia, had pre-existing mental health conditions, with substance use, and sustained their injury through suspected assault or abuse. Injuries in patients with recorded DAMA were more severe. Compared to patients without DAMA, a greater proportion of patients with DAMA were readmitted within 28 days of discharge (13.8 % versus 4.9 %), with failed discharge processes (45.5 %) and infection (18.2 %) being the most frequently recorded reasons. They required readmission to the intensive care unit (20 % versus 8.6 %) with longer lengths of stay. Outcome findings remained similar in a matched cohort analysis between those with and without recorded DAMA. These findings highlight the consequences of DAMA, necessitating primary measures to address modifiable, cultural, and social factors preemptively to prevent DAMA among disadvantaged individuals, and secondary measures to minimize the impact of DAMA (e.g., adequate pain and wound discharge management, follow-up care, community-based treatments, etc.).

Allogeneic hematopoietic stem cell transplantation is a viable therapeutic option for several serious diseases however it is a high-risk procedure because it involves high-toxicity protocols with many adverse effects. Existing factors, such as the underlying disease and nutritional status, may influence the outcome. The objective of this study was to evaluate the Nutritional Risk Index as a prognostic tool by correlating it with body mass index, nutritional status, and clinical outcomes in patients undergoing hematopoietic stem cell transplantation. This single center retrospective study was conducted collected sociodemographic, anthropometric, biochemical, and clinical data before conditioning and 30 days post-transplantation. Statistical analyses were performed using the Mann-Whitney test and Spearman's correlation. Overall survival was estimated using the Kaplan-Meier method, with comparisons conducted via the Gehan-Breslow-Wilcoxon test. A Cox Proportional Hazards regression analysis was employed to identify factors associated with mortality; variables demonstrating a p-value ≤0.20 in the univariate analysis were included in the multivariate model. For all analyses, statistical significance was defined as a p-value <0.05. Seventy-seven participants were included, with an average age of 41 years. According to the nutritional risk index, the entire sample was classified as having severe nutritional risk. The body mass index showed that 6.4 % were malnourished, 19.4 % were obese, and 12.9 % had hypoalbuminemia. The estimated survival curve identified a significant difference for patients aged <45 years with survival being significantly longer (p-value = 0.01). Higher albumin levels (≥3.5) after transplantation were associated with longer survival (p-value = 0.04). Sex, body mass index, albumin level before conditioning, and graft-versus-host disease showed no significant differences in terms of survival. Albumin levels ≥3.5 g/dL after transplantation were marginally associated with a lower mortality risk and malignant disease showed a trend toward increased mortality. These findings underscore the clinical utility of prognostic indices, such as the Nutritional Risk Index and albumin levels, during the pre-transplant period, emphasizing the necessity for early nutritional interventions in hematopoietic stem cell transplantation patients.

Probiotic and prebiotic interventions in burn patients: A systematic review.

Enhancing outcomes for geriatric patients with evaluation of the social determinants of health.

Fish oil supplementation and clinical outcomes in patients with sepsis-associated acute kidney injury: A retrospective cohort study from the MIMIC-IV database.

Ileocaecal resection versus infliximab for ileal Crohn's disease: retrospective 10-year follow-up of the LIR!C trial.

Delandistrogene moxeparvovec is a recombinant adeno-associated virus rhesus isolate serotype 74 vector-based gene therapy that addresses the absence of functional dystrophin in Duchenne muscular dystrophy (DMD). EMBARK is a phase 3, two-part, crossover, randomized, placebo-controlled trial assessing the safety and efficacy of delandistrogene moxeparvovec (single intravenous dose 1.33 × 1014vector genomes/kg) in ambulatory male patients with DMD aged 4 to < 8years; N = 125. One-year results demonstrated the manageable safety of delandistrogene moxeparvovec, consistent with previous clinical trials. The primary endpoint (change from baseline in North Star Ambulatory Assessment [NSAA] total score at 52weeks compared with placebo) did not meet statistical significance. However, key secondary endpoints, comprising timed function tests, suggested slowing or stabilization of disease progression with delandistrogene moxeparvovec, which could become increasingly evident over longer periods of time. We report 2-year follow-up of safety and functional outcomes in patients receiving delandistrogene moxeparvovec in EMBARK part1. As a result of the crossover study design, 2-year functional outcomes of patients receiving delandistrogene moxeparvovec in part1 of EMBARK were compared, by pre-specified analysis, with a matched propensity score-weighted external control (EC). At 2years, EMBARK patients showed statistically significant benefit versus the EC cohort in functional outcomes prognostic for delaying loss of ambulation (NSAA, Time to Rise, 10-m Walk/Run), demonstrating sustained stabilization or slowing of disease progression. Delandistrogene moxeparvovec micro-dystrophin expression and sarcolemmal localization were maintained over 64weeks. No new safety signals were observed between week52 and week104. Between baseline and week104, there were no treatment-related deaths, study discontinuations due to adverse events, or clinically significant complement-mediated adverse events. At 2years, stabilization or slowing of DMD disease progression was observed in ambulatory male patients with DMD aged 4 to < 8years receiving delandistrogene moxeparvovec versus a matched EC cohort. Safety was consistent with EMBARK 1-year data and manageable with appropriate monitoring. GOV: NCT05096221.

Sleep apnoea and its consequences: from animal models to precision medicine.

Long-term outcomes in patients with aortic stenosis and transthyretin cardiac amyloidosis.

Venous invasion in upper tract urothelial carcinoma: Diagnostic features and oncologic outcomes.

Overcoming the leptomeningeal seeding of medulloblastoma by targeting HSP70.

To investigate the influence of different feature aggregation and selection methods on the predictive performance of fluorine-18 fluorodeoxyglucose ( 18 F-FDG) PET radiomics in assessing survival outcomes in patients with lymphoma. This retrospective analysis included 80 patients with histologically confirmed lymphoma, each presenting with at least three lesions on baseline 18 F-FDG PET images. Metabolic tumor volumes were segmented using a standardized uptake value threshold of 4.0. From each lesion, 107 radiomic features were extracted. Of these, 30 features were preselected based on their robustness to variations in tracer uptake time, image reconstruction parameters, and respiratory motion. Six distinct feature aggregation approaches were evaluated in combination with six feature selection methods. Multivariable Cox proportional hazards regression was used to assess the predictive performance of each aggregation-selection strategy for progression-free survival (PFS) and overall survival (OS). All combinations of feature aggregation and selection methods produced statistically significant prognostic models for PFS and OS, with Harrell's concordance indices (C-index) ranging from 0.582 to 0.668 for PFS and from 0.597 to 0.721 for OS. The best predictive performance was achieved using median value aggregation across all individual lesions combined with feature selection via the least absolute shrinkage and selection operator. Integrating clinical variables with radiomic features further improved predictive performance. The prognostic value of 18 F-FDG PET radiomics remained consistent across different feature aggregation and selection strategies. The establishment of standardized analysis workflows is essential to facilitate its clinical implementation in personalized treatment planning for patients with lymphoma.

Aspirin is widely used as an antiplatelet therapy for preventing and managing thrombotic complications in individuals at high risk. Nevertheless, growing evidence indicates that some patients continue to face cardiovascular events, suggesting impaired drug responsiveness or reduced sensitivity to aspirin. This review primarily aims to elucidate a new emerging molecular mechanism underlying this clinical outcome. Recent studies propose that aspirin induces PPARα-dependent overexpression of the Multidrug Resistance Protein 4 (MRP4) transporter, leading to increased extrusion of aspirin and reduced drug efficacy. Several findings support this mechanism: i) MRP4 is associated with resistance to several drugs; ii) it is highly expressed in platelets, which are notably affected by aspirin; iii) it transports organic anions such as aspirin, which has been demonstrated to be a substrate; and iv) aspirin enhances PPARα activity, leading to higher MRP4 gene transcription. Consequently, inhibition of MRP4-mediated aspirin efflux may enhance pharmacological efficacy and prevent platelet aggregation. This review also highlights the potential role of lifelong monitoring in patients on aspirin therapy using platelet function tests to identify those with high residual platelet reactivity (RPR) despite treatment. Such monitoring helps detect inadequate antiplatelet response, guiding clinicians in selecting the most appropriate and personalised therapy, thereby optimising treatment efficacy and reducing the risk of recurrent thrombosis. In conclusion, combining an MRP4 inhibitor with aspirin may represent a promising therapeutic strategy to overcome resistance mechanisms and improve clinical outcomes in patients who exhibit RPR on aspirin and MRP4 overexpression.

Preoperative anxiety is associated with postoperative cardiovascular events, extubation delay, and pain in patients undergoing cardiac surgery: A prospective observational study in Taiwan.

Impact of coding and non-coding SNPs in the FZD8 gene on structural and functional alterations associated with tumorigenesis: A multi-faceted computational approach.

Real-world outcomes in patients with cirrhosis undergoing cholecystectomy: a population-based study.

In FIDELITY, finerenone improved kidney and cardiovascular (CV) outcomes in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines categorise CKD progression risk based on estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR). This FIDELITY post hoc subanalysis investigated KDIGO risk category changes associated with finerenone. Improvement or worsening in KDIGO risk category was defined by variation from baseline, with specified eGFR and UACR changes. Association of these category changes with a CV composite outcome was assessed. Finerenone therapy led to a higher likelihood of KDIGO risk category improvement (odds ratio [OR], month 36: 1.47; 95% confidence interval [CI], 1.31-1.65; p<0.0001) and lower likelihood of worsening (OR, month 36: 0.83; 95% CI, 0.77-0.90; p<0.0001) vs. placebo. Risk category improvement reduced the CV composite outcome risk (hazard ratio [HR]: 0.82; 95% CI, 0.68-0.99; p=0.043) while worsening increased this risk (HR: 1.29; 95% CI, 1.06-1.56; p=0.01). Finerenone therapy is associated with greater improvement and less worsening in KDIGO risk vs. placebo. The category changes are associated with lower risk of CV events in patients with CKD and T2D. FIDELIO-DKD (NCT02540993) and FIGARO-DKD (NCT02545049) are registered with ClinicalTrials.gov (funded by Bayer AG).