Hospital das Clínicas da Universidade Federal de Minas Gerais

Uncertainties persist regarding the allocation of apical lymph nodes in colorectal cancer, the approaches to lymph node dissection and mesocolic excision, which may contribute to inconsistent surgical practices. The aim of this study is to assess surgeons' practices in lymph node dissection and mesocolic excision approaches and to identify areas lacking standardization. A multinational pilot survey of 22 colorectal surgeons from 6 countries was conducted during the FICARE colorectal meeting. The survey consisted of 21 Likert-scale questions on surgical practices and lymph node allocation in colorectal cancer surgery. Majority of the respondents (90.9%) recognized conceptual differences in apical lymph node stratification between right- and left-sided colon cancers, whereas D3 LND for left-sided cancer should include mesocolic tissue along the inferior mesenteric artery from its origin to the last sigmoid artery. Complete lymph node dissection requires excision of mesocolic tissue along inferior mesenteric artery for left colon cancer and superior mesenteric artery for right colon cancer according to 81.8% of respondents. At the same time, 95.5% agreed that intermediate and paracolic lymph nodes are located within a 10-cm resection margin proximally and distally from tumor, while 81.9% of respondents supported the concept of tumor-specific mesocolic excision to be sufficient enough for adequate paracolic and intermediate lymph node dissection. A multinational snapshot showed an existing contraindication in surgeons' perception of lymph node stratification and the variability in mesocolic excision and LND. Further Delphi consensus is needed to prove the suggested concepts.

ABSTRACTAdvanced chronic liver disease (ACLD) remains a major cause of global morbidity and mortality. Preventing hepatic decompensation—both the first event and subsequent recurrences—has become a central therapeutic goal to prolong survival. The transition from the compensated phase (cACLD) to the decompensated phase (dACLD) is driven by clinically significant portal hypertension (CSPH) and continuous exposure to etiologic factors, and is often precipitated by systemic triggers such as infections, portal vein thrombosis, and hepatocellular carcinoma. Thus, effective prevention requires a multidisciplinary strategy combining etiologic control with hemodynamic modulation, supported by vaccination, optimized nutrition and physical activity, judicious endoscopic therapy, and a critical reassessment of antibiotic prophylaxis in the era of antimicrobial resistance. Among non‐selective beta‐blockers (NSBBs), carvedilol—through combined β1/β2 and α1 blockade—achieves a greater reduction in hepatic venous pressure gradient (HVPG) than propranolol and demonstrates superiority in preventing first decompensation. In dACLD, although the effect of NSBBs is attenuated, carvedilol still emerges as the preferred option, given that propranolol shows significantly lower efficacy at this stage. Endoscopic variceal ligation (EVL) remains an alternative for NSBB‐intolerant patients in cACLD and is essential for secondary prophylaxis. Moreover, in dACLD, the combination of EVL with carvedilol is increasingly being explored in Child‐Pugh B/C patients. We provide an overview of pathophysiological mechanisms, risk stratification using non‐invasive tests, and pragmatic prevention strategies across the different stages of disease, emphasizing recompensation, the NSBB “therapeutic window,” and the need to revisit routine antibiotic prophylaxis.

Thestudy aimed to assess theapplicability oftheROSE conceptual framework (Resuscitation, Optimization, Stabilization, Evacuation) for fluid therapy in critically ill pediatric patients, focusing on its distinct phases, prevention offluid accumulation, and clinical outcomes. Aquasi-experimental study was conducted including 122 (retrospective: n = 71; prospective: n = 51) mechanically ventilated and vasoactive-dependent children. Aretrospective cohort was compared with aprospective cohort following structured training on ROSE-guided fluid management. Outcomes included fluid accumulation percentage (FA%), duration ofmechanical ventilation, pediatric intensive care unit (PICU) length ofstay, and need for renal replacement therapy (RRT). Adherence to phase-specific FA% targets was also assessed. FA% was similar between cohorts (retrospective vs. prospective) on PICU days 1, 3, and 10 (median [IQR] 1.8% [0.2-4.3] vs. 1.9% [0.8-3.2], P = 0.934; 5.5% [1.7-10.3] vs. 6.1% [3.8-10.2], P = 0.565; 8.3% [0.8-24.8] vs. 7.2% [2.6-18.7], P = 0.848). By ROSE phase, FA% was comparable in Resuscitation (3.5% [2.0-6.0] vs. 4.7% [2.4-6.9], P = 0.244), Optimization (3.0% [0.1-6.7] vs. 4.2% [1.0-7.9], P = 0.261), and Evacuation (2.5% [-2.6-5.3] vs. 2.4% [-0.0-7.4], P = 0.256), but higher during Stabilization (2.5% [0.0-6.9] vs. 4.2% [2.0-8.9], P = 0.043). Mechanical ventilation, length ofPICU stay, RRT, and fluid elimination were similar. No independent predictors emerged in logistic regression. FA% target adherence rose from 67.9% to 72.4% after ROSE. TheROSE framework in pediatric fluid management is feasible, provides benchmarking for FA% control, and shows promise for individualizing fluid management. Future validation in ROSE-naive centers is warranted.

We thank Huang and colleagues [1] for their thoughtful letter and for highlighting the critical role of non-selective beta-blockers (NSBBs) as a potential effect modifier in the relationship between statin therapy and clinical outcomes in cirrhosis. We agree that the interplay between statins and NSBBs is central to the pharmacotherapy of portal hypertension, and that heterogeneity in NSBB exposure across studies may introduce confounding and contribute to between-study variability. While our original publication [2] partially addressed this issue via a sensitivity analysis for the haemodynamic outcome of hepatic venous pressure gradient (HVPG), we acknowledge that applying similarly rigorous approaches to clinical endpoints would be informative and could further clarify whether the observed benefits of statins are independent of, or synergistic with, concomitant NSBB therapy. In response to their suggestion, we performed a post hoc sensitivity analysis of all-cause mortality and hepatic decompensation, restricting inclusion to the randomised controlled trials (RCTs) where NSBBs were administered as a standardised co-intervention in both study arms [3-6]. Within this NSBB-standardised subset, statin therapy remained significantly associated with lower all-cause mortality (OR 0.39; 95% CI 0.21–0.74; I2 = 0.0%) (Figure 1A). This finding suggests that the survival benefit of statins may be additive to that of NSBBs and could plausibly reflect pleiotropic effects beyond portal pressure reduction, including improvements in liver microvascular function, nitric oxide regeneration and modulation of systemic inflammation. For hepatic decompensation, the NSBB-standardised subset yielded an OR of 0.68 (95% CI 0.46–1.02; I2 = 0.0%) (Figure 1B). Consistent with the overall RCT analysis, this estimate did not reach conventional statistical significance, although the direction of effect remained protective and aligned with the signal observed across observational studies. This is relevant, as the cardiovascular/metabolic benefits of statins typically emerge with prolonged treatment and are well established in long-term follow-up studies [7, 8]. Accordingly, the absence of statistical significance for decompensation in RCTs may reflect limited follow-up and/or power rather than the absence of a biologically meaningful effect, especially in the light of the consistent mortality and haemodynamic signals. We acknowledge, however, that NSBB use is incompletely and inconsistently reported in observational cohorts, which limits the ability to adequately account for this key covariate. Although adjusted analyses were used where available, observational evidence remains susceptible to residual confounding and should be interpreted cautiously. While these findings are encouraging, we recognise that heterogeneity in treatment duration/doses, types of statins used, disease severity/stage and cirrhosis aetiology remain other major limitations of the current evidence base. Adequately powered, large-scale trials with standardised concomitant NSBB therapy, careful phenotyping of portal hypertension stage and sufficient follow-up will be essential to more definitively delineate the independent (and potentially synergistic) effects of statin therapy on clinically meaningful endpoints. In the interim, we continue to support the Baveno VII [9] recommendation to encourage statin use in patients with cirrhosis who have an approved indication, with appropriate caution in decompensated disease. At the same time, we note with excitement that the growing body of evidence raises the possibility that statins may ultimately assume a broader role as disease-modifying agents in cirrhosis. Bernardo de Faria Moraes: conceptualization, writing – original draft, methodology, formal analysis, data curation. Gustavo André Pedral Diniz Leite: conceptualization, investigation. Igor Boechat Silveira: conceptualization, investigation. Gabriel André Pedral Diniz Leite: conceptualization, investigation. Maria Luisa Motta Fonseca: conceptualization, investigation. Leonardo Corrêa Suffert: conceptualization, investigation. Luisa Medeiros Visentini: conceptualization, investigation. Luis Pedro Possapp Beis: conceptualization, investigation. Guilherme Grossi Lopes Cançado: conceptualization, validation, supervision, writing – review and editing, data curation. The authors have nothing to report. The authors have nothing to report. The authors declare no conflicts of interest. This article is linked to Moraes et al. papers. To view these articles, visit https://doi.org/10.1111/apt.70526 and https://doi.org/10.1111/apt.70558. The data that support the findings of this study are available from the corresponding author upon reasonable request.

Introduction This systematic review and meta-analysis aimed to assess the safety and efficacy of oral microbiome therapy (OMT) for the treatment of recurrent Clostridioides difficile infection (CDI). Methods A comprehensive search was performed in PubMed, Cochrane library, Scopus and Embase. All randomized controlled trials (RCTs) meeting predefined inclusion criteria were included. Statistical analysis was performed using R software. Results Three RCTs comprising 469 patients were analyzed, of whom 250 (53%) received OMT and 219 (47%) received placebo. OMT significantly reduced CDI recurrence at week 8 compared to placebo (risk ratio [RR] 0.57; 95% confidence interval [CI] 0.33–0.99; p = 0.04). In exploratory efficacy analyses, no significant differences in recurrence were observed between groups when stratified by prior fidaxomicin use (RR 0.36; 95% CI 0.03–4.01; p = 0.40) or vancomycin use (RR 0.68; 95% CI 0.30–1.55; p = 0.35). Similarly, Firmicutes engraftment at week 1 (mean difference [MD] 41.78; 95% CI −10.55 to 94.11; p = 0.12) and week 8 (MD 34.06; 95% CI −2.49 to 70.61; p = 0.07) did not show statistically significant between-group differences. Safety outcomes and adverse events were comparable between OMT and placebo. Conclusion OMT seems to reduce CDI recurrence at week 8 compared with placebo while demonstrating a comparable safety profile, supporting its role as an effective, well-tolerated therapy for recurrent CDI. New studies are necessary to confirm these findings. Registration The study protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) under registration number CRD420251022230.