Rationale Pediatric-specific ventilator liberation guidelines are lacking despite the many studies exploring elements of extubation readiness testing. The lack of clinical practice guidelines has led to significant and unnecessary variation in methods used to assess pediatric patients’ readiness for extubation. Methods Twenty-six international experts comprised a multiprofessional panel to establish pediatrics-specific ventilator liberation clinical practice guidelines, focusing on acutely hospitalized children receiving invasive mechanical ventilation for more than 24 hours. Eleven key questions were identified and first prioritized using the Modified Convergence of Opinion on Recommendations and Evidence. A systematic review was conducted for questions that did not meet an a priori threshold of ⩾80% agreement, with Grading of Recommendations, Assessment, Development, and Evaluation methodologies applied to develop the guidelines. The panel evaluated the evidence and drafted and voted on the recommendations. Measurements and Main Results Three questions related to systematic screening using an extubation readiness testing bundle and a spontaneous breathing trial as part of the bundle met Modified Convergence of Opinion on Recommendations criteria of ⩾80% agreement. For the remaining eight questions, five systematic reviews yielded 12 recommendations related to the methods and duration of spontaneous breathing trials, measures of respiratory muscle strength, assessment of risk of postextubation upper airway obstruction and its prevention, use of postextubation noninvasive respiratory support, and sedation. Most recommendations were conditional and based on low to very low certainty of evidence. Conclusions This clinical practice guideline provides a conceptual framework with evidence-based recommendations for best practices related to pediatric ventilator liberation.

Background and Aims: Patients with irritable bowel syndrome (IBS) may pursue complementary and alternative medicine (CAM). We conducted a comprehensive systematic review and meta-analysis examining efficacy of CAM vs. placebo or sham in adults with IBS. Methods: Publication databases were searched for randomized controlled trials of CAM therapies (herbal therapy, dietary supplements, mind-body based, body-based, and energyhealing) in adults with IBS. Data were extracted to obtain pooled estimates of mean improvement in abdominal pain (standardized mean difference [SMD]) and relative risk (RR) of overall response using random effects models. Sensitivity and subgroup analyses along with quality assessments were completed. Results: Among 2825 articles identified, 66 were included. Herbal therapy (SMD=0.47, 95% CI: 0.20 to 0.75, I 2 =82%) demonstrated significant benefit over placebo for abdominal pain (low confidence in estimates). Benefit with mind-body based therapy for abdominal pain was of borderline significance (SMD=0.29, 95% CI:-0.01 to 0.59, I 2 =78%). Herbal therapy (RR=1.57, 95% CI: 1.31 to 1.88, I 2 =77%), dietary supplements (RR=1.95, 95% CI: 1.02 to 3.73, I 2 =75%), and mind-body based therapy (RR=1.67, 95% CI: 1.13 to 2.49, I 2 =63%) showed benefit for overall response compared to placebo (low confidence in estimates). Body-based and energy healing therapies demonstrated no significant benefit over placebo or sham for abdominal pain or overall response. Conclusion: CAM therapies such as herbal or dietary supplements and mind-body based approaches may be beneficial for abdominal pain and overall response in IBS. However, overall quality of evidence is low. Rigorous, high quality clinical trials are warranted to investigate CAM in IBS. Billings et al. 3

Imbalanced nutrition is associated with accelerated ageing, possibly mediated by microbiota. An analysis of the circulatory microbiota obtained from the leukocytes of participants in the MRC Twenty-07 general population cohort was performed. We now report that in this cohort, the most biologically aged exhibit a significantly higher abundance of circulatory pathogenic bacteria, including Neisseria, Rothia and Porphyromonas, while those less biologically aged possess more circulatory salutogenic (defined as being supportive of human health and wellbeing) bacteria, including Lactobacillus, Lachnospiraceae UCG-004 and Kocuria. The presence of these salutogenic bactreria is consistent with a capacity to metabolise and produce Nrf2 agonists. We also demonstrate that associated one carbon metabolism, notably betaine levels, did not vary with chronological age, but displayed a difference with socioeconomic position (SEP). Those at lower SEP possessed significantly lower betaine levels indicative of a poorer diet and poorer health span and consistent with reduced global DNA methylation levels in this group. Our data suggest a clear route to improving age related health and resilience based on dietary modulation of the microbiota.

Epigenetic alterations, such as those linked to DNA methylation, may potentially provide molecular explanations for complications associated with altered gene expression in illnesses, such as chronic kidney disease (CKD). Although both DNA hypo- and hypermethylation have been observed in the uremic milieu, this remains only a single aspect of the epigenetic landscape and, thus, of any biochemical dysregulation associated with CKD. Nevertheless, the role of uremia-promoting alterations on the epigenetic landscape regulating gene expression is still a novel and scarcely studied field. Although few studies have actually reported alterations of DNA methylation via methyl donor nutrient intake, emerging evidence indicates that nutritional modification of the microbiome can affect one-carbon metabolism and the capacity to methylate the genome in CKD. In this review, we discuss the nutritional modifications that may affect one-carbon metabolism and the possible impact of methyl donor nutrients on the microbiome, CKD, and its phenotype.

Introduction Resistant starch type‐2 (RS2) can mitigate inflammation and oxidative stress in hemodialysis (HD) patients. However, there is still a lack of knowledge on the impact of the RS2 on the gut microbiota community in these patients. Thus, this study aims to evaluate the effects of enriched RS2 cookies on the gut microbiome in HD patients. Methods and Results This comprises a randomized, double‐blind, placebo‐controlled trial of age‐, sex‐, and BMI‐matched patients and controls. The RS2 group receives enriched RS2 cookies (16 g d‐1 of Hi‐Maize 260, Ingredion) for 4 weeks, while the placebo group received cookies made with manioc flour. Fecal microbiota composition is evaluated by the 16S ribosomal RNA gene. Analysis of the microbiota reveals that Pielou's evenness is significantly decreased after RS2 supplementation. Notably, it is observed that RS2 intervention upregulates significantly 8 Amplicon Sequencing Variants (ASV's), including Roseburia and Ruminococcus gauvreauii, which are short‐chain fatty acids (SCFA) producers. Furthermore, it is associated with the downregulation of 11 ASVs, such as the pro‐inflammatory Dialister. Conclusions RS2 intervention for 4 weeks in HD patients effectively alters SCFA producers in the gut microbiota, suggesting that it could be a good nutritional strategy for patients with chronic kidney disease (CKD) on HD.