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Impact of real-time respiratory function monitoring on neonatal mask ventilation training: a multicentre simulation-based crossover study.

OBJECTIVE: To evaluate whether visibility of respiratory function monitor (RFM) feedback improves mask ventilation performance and influences subsequent ventilation performance during neonatal resuscitation training. DESIGN: multicentre randomised crossover simulation study. PARTICIPANTS: Healthcare professionals involved in neonatal resuscitation training across participating centres. INTERVENTION: Participants performed positive pressure ventilation (PPV) on both term and premature manikins under two conditions: with visible RFM feedback and with the display masked. The order of feedback visibility was randomised. Each participant completed ventilation assessments in both conditions. MAIN OUTCOME MEASURES: Primary outcomes were expired tidal volume (Vte) and mask leak (%). The proportion of breaths within the target Vte range (4-8 mL/kg) was calculated as a performance indicator. Secondary outcomes included variability in Vte and mask leak to assess ventilation stability between conditions. RESULTS: Visible RFM feedback was associated with lower mask leak and improved ventilation stability in the preterm manikin and with tidal volumes entering the target range in the term manikin. Participants initially ventilated with visible feedback maintained performance after feedback removal, suggesting a carry-over learning effect. CONCLUSION: In this multicentre crossover simulation study, visible RFM feedback was associated with changes in mask ventilation performance and evidence of a carry-over learning effect following feedback removal. Real-time visibility of respiratory parameters may strengthen neonatal resuscitation training.

Humans

Efficacy and safety of middle meningeal artery embolization for chronic subdural hematoma: an updated systematic review and meta-analysis focusing on time of intervention.

INTRODUCTION: Chronic subdural hematoma (cSDH) is increasingly prevalent among older adults due to population aging and widespread antithrombotic use. Although burr-hole drainage remains the standard treatment, recurrence rates are substantial. Middle meningeal artery embolization (MMAE) has emerged as an adjunctive strategy to disrupt dural neovascularization and prevent rebleeding. OBJECTIVES: To assess the efficacy and safety of MMAE combined with standard therapy versus standard therapy alone, with stratification by timing of intervention. METHODS: Randomized controlled trials (RCTs) were searched in PubMed, Scopus, and Cochrane Central up to July 2025. Adults with confirmed cSDH were included. The primary outcome was hematoma recurrence or persistence. Secondary outcomes were reoperation, hematoma resorption, serious adverse events, neurological death, mortality, functional independence, and hospital stay. Risk of bias was assessed with RoB-2, and analyses followed PRISMA guidelines (PROSPERO CRD420251112841). RESULTS: Seven RCTs (1,889 patients) were included. Compared with standard therapy, MMAE significantly reduced recurrent or residual cSDH (RR 0.63; 95% CI 0.46-0.85) and reoperation (RR 0.39; 95% CI 0.28-0.56) without increasing serious adverse events (RR 0.87; 95% CI 0.72-1.06), neurological death, mortality, or poor functional outcomes. Hematoma resorption did not differ significantly. Subgroup and sensitivity analyses confirmed the robustness of the results across age, intervention timing, and follow-up duration. CONCLUSION: MMAE combined with standard therapy significantly reduces recurrence and reoperation in cSDH without increasing adverse events or mortality. Benefits appear independent of procedural timing, though larger RCTs with extended follow-up are warranted to define long-term outcomes and optimal use.

Humans

Prophylactic folinic acid prevents pemetrexed myelosuppression: A randomized trial toward safer treatment with chemotherapy in non-small cell lung cancer.

Background Pemetrexed is a cornerstone in advanced non-small cell lung cancer treatment. Although generally well tolerated, severe myelosuppression occurs in 26% of patients. Preventing chemotherapy-associated toxicity has become increasingly important with the introduction of osimertinib combined with pemetrexed-based chemotherapy. Due to substantial toxicity, this regimen is often not administered to frail patients. Folinic acid prophylaxis can mitigate pemetrexed-induced toxicity, however its preventive use has not been routinely studied. We aimed to investigate the efficacy of folinic acid prophylaxis to reduce myelosuppression. Methods Fifty patients treated with pemetrexed were randomized (1:1) to receive pemetrexed with or without oral folinic acid prophylaxis on days 2-4 after each chemotherapy cycle. The primary endpoint was absolute neutrophil count (ANC) after the first chemotherapy cycle. Secondary endpoints included ANC after the second cycle, grade neutropenia, treatment efficacy, renal function and incidence of dose modifications. Results Twenty-four patients received folinic acid and twenty-six served as controls. Higher ANC were observed in the folinic acid group after the first cycle (median 3.79; IQR 2.22-4.93 vs. 1.85; IQR 1.43-3.78; p.

Humans

Psychological consequences of AI-assisted training and the buffering role of mindfulness.

The integration of artificial intelligence (AI) into athletic training is accelerating, yet its psychological implications for athletes remain insufficiently understood. Drawing on the transactional model of stress and the stress-buffering framework of mindfulness, this study examined whether mindfulness training can mitigate adverse psychological responses associated with AI-assisted training. Using a randomized controlled factorial design, 160 collegiate athletes were assigned to AI-assisted training or standard training, with or without concurrent mindfulness intervention, and assessed at baseline, week 4, and week 8. Athletes exposed to AI-assisted training without psychological support exhibited increases in perceived stress and AI dependence over time. In contrast, these stress increases were substantially attenuated when mindfulness training was implemented alongside AI-assisted training. A significant AI × Mindfulness × Time interaction emerged for perceived stress at post-intervention, and difference-in-differences analyses corroborated a robust buffering effect. Mediation analyses further indicated that mindfulness training reduced stress partially through enhancing mindful awareness; a three-wave cross-lagged analysis showed that mindful awareness and stress were reciprocally related over time, with the hypothesized awareness-to-stress pathway remaining robust. Together, these findings suggest that AI-assisted training introduces a distinct form of evaluative pressure, and that mindfulness training may serve as an effective psychological buffer during the adoption of continuous algorithmic performance evaluation systems.

Humans

Comparative effects of pharmacological interventions in the prophylactic treatment of tension-type headache: systematic review and network meta-analysis.

BACKGROUND: Tension-type headache (TTH) is the most common neurological disorder. The comparative effect of pharmacological interventions for TTH prophylaxis remains unclear. We aimed to assess the comparative effects of pharmacological interventions in the prophylactic treatment of TTH. METHODS: Ovid Medline, Embase, and Cochrane were searched from inception to 12 December, 2025. Randomized controlled trials (RCTs) of medications compared to placebo or another medication for preventing TTH were included. The primary outcome was headache days per month. A Bayesian random-effect model was employed as the primary analysis of chronic TTH. RESULTS: Thirty-five RCTs were included, 33 (88.6%) RCTs involved chronic TTH patients, and 24 RCTs provided available data for meta-analysis. Amitriptyline 100 mg presented more reduction of monthly headache days than placebo at 4 and 8 weeks (4 weeks: MD -6.59, 95% CrI -11.22 to -0.64; 8 weeks: MD -6.14, 95% CrI -10.27 to -0.87). BTX-A 100 U can reduce monthly headache days (MD -3.79, 95% CrI -7.16 to -0.33). Amitriptyline 100 mg was the highest-ranked treatment for monthly headache days at 4 (SUCRA 0.85), 8 (SUCRA 0.85), and 24 (SUCRA 0.87) weeks; 12 weeks was lidocaine 25 ml (SUCRA 0.75). Amitriptyline 100 mg and BTX-A 500 U showed a higher adverse event rate than placebo. CONCLUSION: Amitriptyline 100 mg and BTX-A 100 U may be options to reduce monthly headache days in patients with chronic TTH. Given the low to very low certainty of evidence, high risk of bias, and high heterogeneity, more studies are needed. TRIAL REGISTRATION: PROSPERO (CRD42025639586).

Humans

Incidence of Cirrhosis in Fibrotic Metabolic Dysfunction-Associated Steatohepatitis: A Meta-Analysis of Placebo Arms from Randomized Clinical Trials.

BACKGROUNDS AND AIMS: Metabolic dysfunction-associated steatohepatitis (MASH) with stage F2-F3 fibrosis represents the main target population for emerging pharmacotherapies. However, data on short-term progression to cirrhosis (F4) in this group remain limited. We aimed to evaluate the incidence of cirrhosis in placebo-treated patients with fibrotic MASH in randomized controlled trials (RCTs). METHODS: In this single-arm meta-analysis, we systematically searched PubMed and Cochrane Library from inception to December 13, 2024, for pharmacological Phase ≥ 2 RCTs reporting cirrhosis events (detected in liver biopsy or clinical signs) among patients with fibrotic MASH receiving placebo. Incidence rates were pooled using generalized linear mixed models with Clopper-Pearson confidence intervals (CIs). RESULTS: We identified a total of 11 RCTs, including 586 patients with fibrotic MASH. Total follow-up was 657.23 person-years (PYs), with 83 cirrhosis events reported. The pooled incidence rate was 13.09 per 100 PYs (95% CI 7.81 to 21.12, I2 = 75.6%, τ2 = 0.682). In subgroup analysis, the incidence of cirrhosis was 3.40 per 100 PYs in MASH F2 (95% CI 1.10 to 10.02, I2 = 0%, τ2 = 0) and 17.90 per 100 PYs (95% CI 10.63 to 28.55, I2 = 70.2%, τ2 = 0.561) in MASH F3, with significant differences between stages (p = 0.006). Sensitivity analyses showed consistent estimates. Most RCTs were judged to have a low risk of bias. CONCLUSIONS: This study provides stage-specific data on cirrhosis incidence in fibrotic MASH, highlighting the high short-term risk associated with MASH F3 in trial settings. These data may inform benchmarks to guide event expectations, enrichment strategies, sample size assumptions, and the interpretation of future MASH clinical trials.

Humans

Effects of blood flow restriction training combined with resistance training on lower-limb strength and sport-specific performance in athletes: a systematic review and meta-analysis.

BACKGROUND: In contemporary sports science, athletes and coaches continuously explore strategies to reduce training load and injury risk while increasing muscular strength and sport-specific performance. This meta-analysis evaluated the effects of blood flow restriction training (BFRT) combined with resistance training (RT) on lower-limb muscle strength and sport-specific performance in athletes. METHODS: Relevant randomized controlled trials (RCTs) were systematically searched across major databases (e.g. PubMed, Web of Science, Cochrane, CNKI, Wanfang Data, and Embase) from inception until November 2024. Two independent reviewers carefully assessed the studies. Data analysis was carried out using RevMan 5.4 software, which included heterogeneity testing, meta-analysis, subgroup analysis, and assessment of publication bias. RESULTS: Ten RCTs (181 athletes; 91 in the BFRT and RT group, 90 in the control group) were included. Outcomes determined BFRT combined with RT yielded notable enhancements in lower-limb muscle strength (SMD = 1.09, 95% CI [0.52, 1.66], p&#x2009;<&#x2009;0.05) and muscle hypertrophy (MD = 1.09, 95% CI [0.10, 2.09], p&#x2009;<&#x2009;0.05) compared to control training. However, no significant improvement in sport-specific performance was found (SMD = 0.11, 95% CI [-0.18, 0.40], p&#x2009;=&#x2009;0.46). Substantial heterogeneity was observed for strength outcomes (I2 = 75%), whereas low heterogeneity was observed for sport-specific performance and hypertrophy outcomes (I2 = 0%). No evidence of significant publication bias was detected. CONCLUSION: BFRT combined with RT appears to provide effective augmentation of lower-limb muscle strength and hypertrophy in athletes compared to RT or conventional training alone. It may be prudent to integrate this approach systematically into training cycles to optimize physiological muscle stimulation and training outcomes, despite not directly improving sport-specific performance.

Humans

Use of wearable technologies for physical activity promotion in older adults: A systematic review.

This systematic review, conducted according to PRISMA guidelines and registered in PROSPERO (CRD420251055299), examined the use of wearable technologies for promoting physical activity (PA) in adults aged 60 years and older. Searches across five databases (PubMed, Scopus, Web of Science, CINAHL, Cochrane) identified 2438 records, of which only six randomized controlled trials published between 2021 and 2025 met inclusion criteria, with sample sizes ranging from 36 to 551 participants and mean ages between 65 and 79 years. Given the small number of included studies, findings should be interpreted as preliminary. The studies ranged from the standalone use of commercial trackers (Fitbit, Polar, ActiGraph) to multicomponent interventions combining wearables with physiotherapist feedback, telephone counseling, web-based platforms, or interactive cognitive-motor training. Wearables used alone, as in the REACT trial, produced small or non-significant PA effects. In contrast, interventions integrating devices with personalized feedback, professional support, or digital platforms, such as PROMOTE and TASMANIA, were associated with more consistent improvements in PA, physical function, and cognitive outcomes. Multicomponent programs, such as PEER and ICMT, reported broader benefits, including cognition, balance, and reductions in sedentary behavior, though these findings derive from individual trials and require replication. Risk of bias, assessed with the Cochrane Risk of Bias tool version 2 (RoB 2.0), was rated as "some concerns" for five studies and low for only one, mainly due to gaps in randomization reporting, missing data, and lack of preregistration. Tentatively, and based on a very limited evidence base, wearables may have greater impact when embedded within broader behavioral systems, incorporating feedback, coaching, or interactive components, rather than when used in isolation as passive monitoring tools. Adherence and psychosocial outcomes appeared related to comfort and perceived usefulness among older adults, though larger and more robust trials are needed to confirm these patterns.

Humans

A First-in-Japanese Phase 1, Double-Blind, Placebo-Controlled, Parallel-Cohort Study of Sefaxersen, an Antisense Oligonucleotide Targeting Complement Factor B, in Healthy Participants.

Increased activity in the complement alternative pathway (AP) plays a key role in diseases such as IgA nephropathy (IgAN). This first-in-Japanese double-blind Phase 1 study investigated the pharmacokinetics (PK), pharmacodynamics (PD), safety, and tolerability of sefaxersen (RO7434656), an antisense oligonucleotide targeting complement factor B messenger RNA. Healthy participants were randomized equally into four cohorts: placebo or sefaxersen 20, 40, or 70&#xa0;mg. The PK, PD, and safety endpoints were monitored throughout the study and during the 90-day follow-up period. All 24 participants completed the study, with no new safety signals or clinically meaningful changes in blood chemistry, electrocardiogram, or vital signs observed. Plasma sefaxersen concentration demonstrated a biphasic PK profile, characterized by an initial rapid decline followed by a slow elimination. Sefaxersen decreased PD markers related to the complement AP selectively, without affecting the classical pathway, in a dose-dependent manner, and the PD effects persisted over 2 to 3 months. Sefaxersen was well tolerated by healthy Japanese participants, with a manageable safety profile. These findings support the inclusion of Japanese patients with IgAN in the global Phase 3 study (IMAGINATION, NCT05797610).

Humans

Anti-inflammatory agents after hip and shoulder arthroplasty: A systematic review and meta-analysis.

BACKGROUND: Postoperative inflammation after arthroplasty contributes to pain, delayed mobilization and prolonged hospitalization. Recent randomized trials have evaluated pharmacological anti-inflammatory strategies within contemporary enhanced recovery pathways, but evidence after hip and shoulder arthroplasty remains scattered across different drug classes and perioperative regimens. OBJECTIVES: To synthesize recent randomized controlled trial (RCT) evidence on perioperative anti-inflammatory agents after hip and shoulder arthroplasty. METHODS: PubMed, Embase, Cochrane Library and Web of Science were searched for English-language RCTs published from January 2020 to March 2026. The 2020-2026 window was selected to update evidence generated under modern arthroplasty, anesthesia, multimodal analgesia and enhanced recovery after surgery (ERAS) pathways. Eligible trials included adults undergoing hip or shoulder arthroplasty and compared corticosteroids, cyclooxygenase-2 (COX-2) inhibitors, nonsteroidal anti-inflammatory drug (NSAID)-based/local anti-inflammatory regimens, or related anti-inflammatory interventions with placebo, saline, no treatment, or the same regimen without the target component. Weighted mean differences (WMDs) were pooled using random-effects models. RESULTS: Nine RCTs involving 800 patients were included. Anti-inflammatory interventions significantly reduced postoperative C-reactive protein (CRP) [WMD=-32.18, 95% confidence interval (CI) (-41.16, -23.21), P<0.001], interleukin-6 (IL-6) [WMD=-31.25, 95% CI (-41.79, -20.77), P<0.001], rest pain [WMD=-0.41, 95% CI (-0.58, -0.23), P<0.001], activity pain [WMD=-0.56, 95% CI (-0.83, -0.29), P<0.001] and hospital stay [WMD=-0.54, 95% CI (-0.92, -0.15), P=0.006]. CONCLUSION: Recent RCT evidence suggests that perioperative anti-inflammatory interventions can attenuate early inflammatory responses and improve short-term pain and recovery after hip and shoulder arthroplasty. Because data were limited and clinically heterogeneous, the findings should not be interpreted as evidence favoring a specific drug class, dose, route, or timing.

Humans

Impact of subthreshold troponin levels and temporal trends on short term adverse cardiovascular outcomes in patients discharged from the emergency department: a RACE-IT trial substudy.

BACKGROUND: High-sensitivity cardiac troponin I assays enable early exclusion of myocardial infarction in the emergency department. However, the clinical implications of detectable troponin values below the 99th percentile upper reference limit (4-18 ng/L) remain unclear. OBJECTIVE: To assess the association between subthreshold troponin levels and 30-day outcomes in patients from the RACE-IT trial, using exact troponin values when available. METHODS: This post-hoc analysis of the RACE-IT stepped-wedge randomized controlled trial included patients with troponin&#x2009;&#x2264;&#x2009;18 ng/L across nine EDs. Patients were stratified by initial troponin, peak value, absolute change, and percent change. The primary outcome was a 30-day composite of all-cause death, acute MI, percutaneous coronary intervention, and coronary artery bypass grafting. Logistic regression analysis after adjusting for age, sex, race, and coronary artery disease was performed. RESULTS: Among 19,194 patients with troponin&#x2009;&#x2264;&#x2009;18 ng/L, 117 (0.6%) experienced the composite outcome. Higher troponin levels were associated with increased event rates in unadjusted analyses. Adjusted analyses showed no independent associations overall, though patients whose highest troponin values fell within the&#x2009;&#x2265;&#x2009;11-&#x2009;&#x2264;&#x2009;18 ng/L range continued to demonstrate significantly worse outcomes than those with lower peak levels. Elevated troponin values correlated with older age, male sex, and greater comorbidity burden. CONCLUSION: In this post-hoc analysis of patients with troponin values below the 99th percentile URL, absolute levels and temporal changes were not independently associated with 30-day adverse outcomes. These findings support the use of subthreshold troponin values in rapid rule-out protocols, emphasizing the need to consider clinical context and comorbidities in risk assessment.

Humans

Efficacy of Mindfulness-Based Interventions on Anxiety and Sleep Quality in Patients with Breast Cancer: A Systematic Review and Meta-Analysis.

INTRODUCTION: Patients with breast cancer commonly experience anxiety and sleep disturbance during and after treatment, and these symptoms are closely interrelated, negatively affecting the quality of life. Mindfulness-based interventions (MBIs) have been increasingly used as a nonpharmacological supportive approach. This systematic review and meta-analysis aimed to evaluate the effects of MBIs on anxiety and sleep quality in patients with breast cancer. METHODS: A systematic search of PubMed, Web of Science, Cochrane Library, CINAHL, and Embase was conducted up to May 15, 2025. Random-effects meta-analysis was used to estimate standardized mean differences (SMDs) with 95% confidence intervals (CIs). Risk of bias was assessed using the Cochrane RoB 2.0, and the certainty of evidence was evaluated with Grading of Recommendations, Assessment, Development, and Evaluation. RESULTS: Twenty-four randomized controlled trials (RCTs) including 3,212 participants were analyzed. MBIs significantly reduced anxiety compared with control groups receiving usual care, no intervention, or wait-list conditions (SMD: -0.47, 95% CI: -0.62 to -0.32), whereas no significant effect was observed for sleep quality. Subgroup analysis indicated that intervention duration accounted for 55.5% of the heterogeneity in anxiety outcomes. All studies were rated as having some concerns regarding risk of bias, primarily due to self-reported outcomes and lack of blinding. Certainty of evidence was moderate for anxiety and low for sleep quality. DISCUSSION: MBIs appear to be effective in reducing anxiety among patients with breast cancer; however, no significant effect was observed for sleep quality. All included studies were rated as having some concerns regarding risk of bias, and the limited reporting of adverse events represents a limitation of the evidence. In addition, substantial heterogeneity in sleep quality outcomes and the limited number of included RCTs restrict exploration of heterogeneity sources and limit generalizability. Further high-quality well-designed RCTs are needed to strengthen and confirm the evidence.

Female

Artificial intelligence in genitourinary oncology: publication trends and systematic review.

OBJECTIVE: To conduct an analysis of publication trends and a systematic review of randomized controlled trials (RCTs) to characterize the current state of artificial intelligence (AI) use in genitourinary (GU) oncology, as AI has emerged as a transformative tool in healthcare with potential applications in diagnostics, treatment planning, and prognostication. METHODS: We searched the Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica dataBASE (EMBASE; Ovid), and Cumulative Index to Nursing and Allied Health Literature (CINAHL) Ultimate for studies related to AI and GU oncology, excluding non-English papers, non-human studies, review articles, and articles using AI solely for manuscript writing. Publication trends were analysed from 2013 to 2023 and categorized by study design and cancer type. RCTs were evaluated through systematic review using Covidence (Veritas Health Innovation Ltd, Melbourne, Victoria, Australia) for screening and data extraction. Two reviewers independently assessed all studies, with risk of bias (RoB) evaluated using the Cochrane RoB 2.0 tool. RESULTS: Of 2409 articles identified, 1220 met inclusion criteria. These included 962 retrospective articles, 175 prospective studies, 79 studies with combined retrospective/prospective methods, and four RCTs. Studies most commonly addressed prostate (n&#x2009;=&#x2009;923), renal (n&#x2009;=&#x2009;274), and urothelial (n&#x2009;=&#x2009;194) cancers. Publications grew from 14 in 2013 to 362 in 2023, with substantial acceleration in 2019. Four RCTs were identified - one in urothelial cancer and three in prostate cancer. Two RCTs evaluated AI-based diagnostics, demonstrating improved performance over conventional methods; the remaining two RCTs evaluated AI in prognostication and treatment planning, showing improved gains in imaging interpretation and operational efficiency. RoB varied across studies, primarily related to randomisation and deviations from intended interventions. CONCLUSIONS: Artificial intelligence research in GU oncology has grown, although high-level evidence from RCTs remains limited. Existing trials underscore AI's promise in diagnostics, prognostication, and treatment planning, and the rapidly evolving nature of this field warrants continued prospective investigation.

Humans

Maternal vaccination with RSVpreF and risk of hypertensive disorders of pregnancy: a systematic review and meta-analysis.

BACKGROUND: A bivalent respiratory syncytial virus (RSV) prefusion F protein-based vaccine (RSVpreF) was approved in the United States in August 2023 for use during pregnancy to prevent infant RSV-associated lower respiratory tract disease. The pivotal phase 3 trial identified a numerical imbalance in hypertensive disorders of pregnancy (HDP) that did not reach statistical significance; postmarketing observational studies have since reported inconsistent findings. We conducted a systematic review and meta-analysis to assess this association. METHODS: We searched MEDLINE, Embase, CENTRAL, Scopus, ClinicalTrials.gov, and WHO ICTRP from inception to Jan 26, 2026, for randomized controlled trials (RCTs) and observational studies comparing HDP outcomes in RSVpreF-vaccinated versus unvaccinated or placebo-receiving pregnant individuals. Unadjusted risk ratios (RRs) were pooled using a random-effects model; adjusted estimates from observational studies were pooled separately by inverse variance methods. This study is registered with PROSPERO (CRD420251026835). RESULTS: Nine studies were included (3 RCTs, 6 retrospective cohort studies; n&#xa0;=&#xa0;148,267). RSVpreF vaccination was associated with a small but statistically significant increase in overall HDP risk (RR 1&#xb7;08, 95% CI 1&#xb7;02-1&#xb7;13; p&#xa0;=&#xa0;0&#xb7;004; I2&#xa0;=&#xa0;44%), driven by the observational studies group (1&#xb7;08, 1&#xb7;02-1&#xb7;14; I2&#xa0;=&#xa0;61%); RCTs showed a directionally consistent but non-significant RR (1&#xb7;12, 0&#xb7;87-1&#xb7;43; I2&#xa0;=&#xa0;0%). The association was attributable to gestational hypertension, with no significant association for preeclampsia/eclampsia. CONCLUSION: Maternal RSVpreF vaccination was associated with a small increase in HDP attributable to gestational hypertension and driven primarily by observational studies, in which residual confounding remains possible. The benefits of infant RSV prevention remain substantial, and these findings support continued postmarketing surveillance and informed shared decision-making.

Humans

Gut microbiota and metabolic alterations in participants with flatulence identify Faecalibacterium prausnitzii as a key microbial target for clinical intervention.

Flatulence is closely associated with gut dysbiosis, yet the characteristic microbial signatures, metabolic alterations, and actionable intervention targets remain unclear. This limited mechanistic understanding has hindered the development of precise microbiota-based strategies for managing flatulence. Here, we found that participants with flatulence exhibited marked shifts in gut microbial functions and fecal metabolic profiles compared with healthy controls, characterized by enhanced abnormal fermentation, enrichment of oxidative stress-related functions, elevated low-grade inflammatory signatures, and reduced anti-inflammatory and mucosal-protective metabolic features. Faecalibacterium prausnitzii was significantly negatively associated with the high-gas-producing phenotype. In vitro replenishment experiments further validated the role of F. prausnitzii in reducing gas production, promoting butyrate generation, and remodeling butyrate-associated microbial communities. Based on microbial interaction analysis, we identified Bifidobacterium longum CCFM1319 as a candidate strain for targeting F. prausnitzii. In a double-blind, randomized, placebo-controlled clinical trial, supplementation with B. longum CCFM1319 significantly increased intestinal F. prausnitzii abundance and improved flatulence-related symptoms. Collectively, these findings reveal the microbiota and metabolic dysbiosis underlying flatulence, highlight the key regulatory role of F. prausnitzii, and lays the foundation for targeted microbiota-based intervention strategies for flatulence.

Humans

A 7-mm Covered TIPS Reduces&#xa0;Hepatic Encephalopathy Without Increasing Rebleeding in Cirrhotic Patients With Small Liver: A Randomized Study.

BACKGROUND/AIMS: International guidelines recommend initiating transjugular intrahepatic portosystemic shunt (TIPS) placement with an 8-mm stent. However, there is an evident lack of randomized controlled trials evaluating TIPS diameters <&#x2009;8&#x2009;mm in cirrhotic patients with a relatively small liver. The aim of this study was to determine whether 7&#x2009;mm-covered TIPS, compared with 8-mm stents, could achieve comparable shunt function with a lower incidence of hepatic encephalopathy (HE). METHODS: In this multicenter randomized controlled trial, patients with cirrhosis and relatively small liver were randomized 1:1 to receive TIPS with a 7-mm (n&#x2009;=&#x2009;92) or 8-mm (n&#x2009;=&#x2009;92) covered stent to prevent variceal rebleeding. The primary endpoint was the incidence of overt HE after randomization. All-cause rebleeding, orthotopic liver transplantation (OLT)-free survival and a composite of these outcomes, were designated as secondary endpoints. RESULTS: Among the 184 enrolled patients, the predominant etiologies of liver cirrhosis were hepatitis B virus infection (56.0%) and alcohol-related liver disease (20.7%). Over a median follow-up of 26.5&#x2009;months, overt HE occurred in 19 patients (20.7%) in the 7-mm group and 33 patients (35.9%) in the 8-mm group. The 2-year cumulative incidence of overt HE was significantly lower in the 7-mm group than in the 8-mm group (21.4% vs. 37.2%, p&#x2009;=&#x2009;0.02). Stent diameter, post-TIPS portosystemic pressure gradient, pre-covert HE and MELD-Na score were identified as independent risk factors for overt HE. The rates of shunt dysfunction were statistically similar between groups (8.7% vs. 8.7%, p&#x2009;=&#x2009;1.0), as were 2-year rebleeding rates (10.9% vs. 9.8%, p&#x2009;=&#x2009;0.81) and OLT-free survival rates (91.3% vs. 88.0%, p&#x2009;=&#x2009;0.82). CONCLUSIONS: A 7-mm covered TIPS demonstrated comparable shunt function to an 8-mm covered stents, with a significantly lower risk of overt HE. These findings support consideration of 7-mm TIPS stents for preventing variceal rebleeding in cirrhotic patients with a small liver who are undergoing TIPS. TRAIL REGISTRATION: ClinicalTrials.gov, NCT02541825.

Humans

Comparison of three tracking methods to assess usage of two pediatric powered mobility devices for young children with cerebral palsy.

Powered mobility devices are underutilized for promoting self-initiated mobility in young children with cerebral palsy due to prioritization of walking, caregiver effort, device characteristics, and environmental factors. Understanding device usage patterns is important to assess the impact of powered mobility interventions on child outcomes. As part of clinical trial (NCT04684576), three objective tracking methods including integrated loggers, Global Positioning System trackers (GPST), and caregiver reported activity logs (CRAL) were compared to provide insights into device usage patterns. Metrics included play session frequency, session duration, total usage minutes, and unique usage days for two powered mobility devices: Modified Ride-on Cars (MROC) and the Permobil Explorer Mini (EM). Twelve children with cerebral palsy used each device for eight consecutive weeks in home and community settings (16&#x2009;weeks total), with device ordered randomized. Results showed no significant differences among tracking methods for the MROC. For the EM, only session duration differed between GPST and CRAL. Correlation analysis revealed variable relationships amongst tracking methods for both devices. The EM was used more frequently than the MROC, with significantly greater total usage minutes and session duration via CRAL, not GPST. The findings highlight the need for reliable tracking technologies that can be used across powered mobility devices.

Child, Preschool

Comparing Clinical and Cytokine Profiling of Genital Inflammation as Predictors of HIV Acquisition in Women.

BACKGROUND: Inflammation in the female genital tract is a key risk factor for HIV acquisition, but it remains unclear whether clinical or immunological measures best predict risk. We aimed to compare HIV acquisition among women with clinically and/or immunologically defined inflammation. SETTING: HIV-uninfected women enrolled in the CAPRISA 004 tenofovir gel randomized controlled trial in South Africa were followed for up to 34 months. METHODS: We analyzed data from 889 women, with cytokine measurements available for 774 participants. Clinical genital abnormalities were assessed at scheduled visits, and 9 cytokines were measured in cervicovaginal lavage samples. HIV incidence was compared across categories of clinical and immunological inflammation using time varying Cox proportional hazards models, adjusting for relevant covariates. RESULTS: Immunological inflammation, defined as &#x2265;9 elevated cytokines, was present in 18% (140/774) of women. Among specific clinical signs, abnormal genital discharge (adjusted hazard ratio: 2.67, 95% confidence interval [CI]: 1.14 to 6.23, P = 0.024) and cervicitis (adjusted hazard ratio: 10.34, 95% CI: 2.46 to 43.65, P = 0.001) were significantly associated with increased HIV acquisition. Women with both clinical and immunological inflammation had the highest risk of HIV acquisition, with adjusted hazard ratios of 2.08 (95% CI: 1.10 to 3.91, P = 0.022) and 2.46 (95% CI: 1.21 to 5.03, P = 0.013), respectively. CONCLUSIONS: Clinical and immunological definitions of inflammation were each independently associated with increased HIV acquisition risk and combined, they reflected greater susceptibility. These findings highlight the important role of genital inflammation in women's HIV susceptibility, suggesting that clinical signs may provide practical early indicators of risk even as cytokine profiles provide more sensitive measures of underlying inflammation.

Humans