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Longitudinal functional trajectory and surgical outcomes after intracranial meningioma resection: implications for surgical decision-making in older patients.

OBJECTIVE: As the population ages, meningiomas are increasingly encountered in older patients, yet longitudinal functional outcomes following surgery across age groups remain incompletely characterized. This study evaluated age-related differences in clinical and tumor characteristics, functional trajectory, and surgical outcomes. METHODS: This was a retrospective cohort study of 396 consecutive patients who underwent surgery for intracranial meningiomas at a single academic center between January 2023 and September 2025. Patients were stratified into 5 age groups (< 65, 65-69, 70-74, 75-79, and &#x2265; 80 years). Neurological deficits and Karnofsky Performance Status (KPS) were assessed preoperatively, at discharge, and at last follow-up. Logistic regression analyses identified predictors of prolonged length of stay (LOS) (> 5 days) and poor functional outcome at discharge (KPS < 80). RESULTS: Older patients presented with greater comorbidity burden, larger tumors, and lower preoperative KPS (all p < 0.05), while gross-total resection was achieved at comparable rates across all age groups (p = 0.504). A clinically meaningful inflection point was observed around age 75 years, with KPS < 80 at discharge rising from 7.4% and 9.7% in the < 65-year and 70- to 74-year subgroups and to 36.2% and 57.1% in the 75- to 79-year and &#x2265; 80-year subgroups (p < 0.001), and median LOS increased from 4 days in the younger groups to 9 and 7 days in the 75- to 79-year and &#x2265; 80-year groups (p < 0.001). However, recovery rates among patients who experienced functional decline at discharge were comparable across age strata. On multivariable analysis, independent predictors of prolonged LOS were age &#x2265; 75 years (OR 2.31, p = 0.019), diabetes mellitus (OR 2.85, p = 0.004), posterior fossa location (OR 2.1, p = 0.008), tumor diameter (OR 1.33, p < 0.001), postoperative edema (OR 2.58, p = 0.015), and neurosurgical complications (OR 3.18, p = 0.002). Independent predictors of poor functional outcome at discharge were age &#x2265; 75 years (OR 5.84, p < 0.001), lower preoperative KPS (OR 2.8, p < 0.001), posterior fossa location (OR 3.72, p = 0.003), neurosurgical complications (OR 3.56, p = 0.008), and recurrent meningioma (OR 2.89, p = 0.025). Among 70 endoscopic endonasal approach patients, higher preoperative deficit burden and subtotal resection rates were observed compared to open craniotomy, though overall functional outcomes were comparable. CONCLUSIONS: Surgical risk in meningioma resection increases from age 75 years onwards, yet recovery capacity following initial functional decline remains similar across all age groups. Preoperative functional status, tumor location, comorbidity burden, and recurrence history should guide surgical decision-making rather than age alone.

Humans

Effectiveness of an educational video for caregivers of children with neurogenic bladder: A randomized controlled trial.

BACKGROUND: The complexity of neurogenic bladder (NGB) management underscores the importance of caregiver education, yet high-quality education materials remain scarce. This study aims to assess the effectiveness and acceptability of an educational video designed to improve knowledge about NGB among caregivers of children with this condition. METHODS: We identified English-speaking caregivers of patients aged zero to 18 years, diagnosed with NGB, without prior major bladder reconstructive surgery, who received care at our institution from 2018 to 2022. Caregivers were randomly assigned into control or video groups using a block randomization model based on age. The control arm completed a six-item knowledge assessment before viewing the video, while the video group watched the video first. All participants rated the video's acceptability. Qualitative analysis of the open-ended responses to the acceptability questionnaire followed principles of thematic analysis. RESULTS: Of 409 eligible participants, 106 (25.9%) completed the study. Video (n = 48) and control (n = 58) groups were demographically similar. In the video group, 64.6% answered correctly all questions in the knowledge questionnaire, compared to 31% in the control group. After adjusting for patient age, caregivers in the video group were more likely to answer any question in the knowledge assessment correctly (relative probability: 1.13, 95% CI [1.06, 1.21], p < 0.01). Evidence for a difference in correct response rate among individual questions was strongest for question #1, which asked about common urological conditions for which NGB patients are at higher risk (95.8% vs. 79.3%, p = 0.01), and question #6, which asked about indications for bladder surgery (87.5% vs. 67.2%, p = 0.01), with the video group more likely to answer correctly for both questions. Qualitative analysis identified three major themes regarding parents' acceptance of the educational video: 1) attitudes towards video content and presentation, 2) usefulness of video as an educational tool, and 3) future directions. CONCLUSIONS: Our study found that an educational video about NGB effectively enhanced parental understanding of the condition and was deemed acceptable by parents as an introductory educational tool. The literature shows the benefit of using technology and visual aids to enhance health literacy for patients and caregivers, a key first step towards optimizing health outcomes for pediatric urologic patients.

Humans

Positive conversion of latent tuberculosis screening in patients with inflammatory bowel disease on antitumor necrosis factor alpha drugs: a systematic review and meta-analysis.

Inflammatory bowel disease (IBD) patients undergoing antitumor necrosis factor-alpha (anti-TNF) therapy are at increased risk of developing tuberculosis (TB), making screening before anti-TNF initiation mandatory. Repeated screening during treatment is not yet recommended because of a lack of studies to support this practice. We aimed to determine the proportion of patients who develop latent TB during anti-TNF therapy. We systematically searched studies from MEDLINE, Embase, and Lilacs, and performed a single-arm meta-analysis investigating the positive conversion rate in IBD patients under anti-TNF therapy with previous negative TB screening. We calculated the combined proportion with 95% confidence interval, using the random-effects model. A P value less than 0.05 was considered statistically significant for subgroup differences. We included 13 studies from nine countries with 1153 patients. The overall positive conversion rate was 9.20%. Portugal had 18.01% of positive conversion, Spain 4.51%, and the USA 1.11%. Tests for subgroup differences were statistically significant for subgroup analysis by country and consistency of test used (performig same test as baseline). Subgroup analyses by continent, study design, or specific test (tuberculin skin test or interferon-gamma release assay) showed no statistical difference. Meta-regression analysis showed a significant positive association between positive conversion and TB incidence. In conclusion, IBD patients on anti-TNF therapy can have a positive conversion rate of 9.20%. Higher conversion rates were seen in European and Asian studies compared with those in the Americas (particularly the USA). TB prevention strategies should, therefore, be individualized and based on geographic location and risk factors.

Humans

Integrated exome and mitochondrial genome sequencing reveals the genetic landscape of primary mitochondrial diseases: findings from a large Tunisian cohort.

Primary mitochondrial diseases are a heterogeneous group of neurometabolic disorders recognized as the most common metabolic genetic diseases. They manifest at any age, affecting any tissue or organ, especially those with high energy demands, and are caused by pathogenic variants in both mitochondrial and nuclear genomes. Here, we aimed to describe the genetic spectrum of a Tunisian pediatric cohort with suspected mitochondrial diseases. We recruited 47 unrelated families who underwent exome sequencing as a first-tier test followed by whole mitochondrial genome sequencing for unsolved cases. Dedicated bioinformatic pipelines and prediction tools were used to determine the potential disease-causing variants. Sanger sequencing confirmed the presence and segregation within parents. For the newly identified variants, structural modeling was conducted to study the impact of these variants on protein structure and motions. Dual genome sequencing yielded a molecular diagnosis in 33/47 families (70%) and 18/47 (38%) showed disease-causing variants in genes encoding mitochondrial proteins. Among them, four families disclosed novel variants in FASTKD2, SERAC1 and GATB, which were supported by in-depth in silico and structural analyses demonstrating their deleterious effect. The remaining families (32%, 15/47) disclosed other metabolic and neurological disorders. An exome-first strategy delivers a high diagnostic yield in Tunisia, where consanguinity remains high and simultaneously captures mitochondrial and non-mitochondrial etiologies. Mitochondrial sequencing remains indispensable in the case of an inconclusive exome. Thus, our data expand the clinical and genetic spectrum of primary mitochondrial diseases in Tunisia, an underrepresented and admixed population.

Humans

Closed-loop vasopressor systems for hemodynamic control in perioperative and critical care settings: a systematic review and meta-analysis.

Maintaining mean arterial pressure (MAP) within a predefined target is central to haemodynamic management in surgical and critically ill adults receiving vasopressors. Closed-loop vasopressor (CLV) systems automate titration to optimise blood pressure control, but their clinical effectiveness remains uncertain. We performed a systematic review and meta-analysis comparing CLV with manual titration. This PRISMA 2020-compliant review was prospectively registered in PROSPERO (CRD420250655697). MEDLINE, Embase, Scopus, Web of Science, CENTRAL, and the Cochrane Library were searched (January 2000-June 2025). Randomised controlled trials enrolling adults receiving vasopressors in perioperative or intensive care settings were included. Primary outcomes were time within the MAP target range and time spent in hypotension or hypertension. Risk of bias was assessed using RoB 2.0 and certainty of evidence using GRADE. Random- or fixed-effects models were selected according to heterogeneity. Six randomized controlled trials (215 patients) were included in the systematic review, whereas five perioperative trials contributed to the meta-analysis of haemodynamic control outcomes, and one ICU-based study was summarized narratively because it did not report comparable MAP control endpoints. CLV increased time within the MAP target range (mean difference [MD] 33.94%, 95% CI 20.41-47.46; I2&#x2009;=&#x2009;77%) and reduced time in hypotension (MD&#x2009;-&#x2009;18.24%, 95% CI&#x2009;-&#x2009;28.95 to&#x2009;-&#x2009;7.53; I2&#x2009;=&#x2009;73%). There was no significant difference in time in hypertension, cumulative norepinephrine dose, or major/minor adverse events. ICU length of stay was not pooled because of clinical and methodological heterogeneity. Certainty of evidence ranged from low to high (moderate for haemodynamic control outcomes). CLV systems improved haemodynamic control, primarily in perioperative settings,&#xa0;but heterogeneity and small samples limit confidence in effect size and generalisability.&#xa0;Evidence in critically ill populations remains limited, and larger trials are needed to determine whether improvements in these physiological surrogate endpoints translate into meaningful patient-centred outcomes.

Humans

Efficacy and safety of human albumin combined with furosemide in acute decompensated heart failure with hepatic dysfunction.

BACKGROUND: Congestion is the most common clinical presentation on admission of patients with acute decompensated heart failure (ADHF). Finding effective ways to alleviate congestion has become a pivotal management step. This study sought to investigate the efficacy and safety of intravenous (IV) albumin use in conjunction with furosemide in patients hospitalized for ADHF with hepatic dysfunction in terms of subjective regression of congestion symptoms and worsening renal function. METHODS: This prospective, open-label, randomized-pragmatic trial recruited 241 patients with hepatic dysfunction hospitalized for ADHF. Patients (78 years, 54% female) were assigned to receive IV albumin with furosemide or IV furosemide alone. The coprimary study endpoints were patients' global assessment of symptoms score, quantified as the area under the curve (AUC) of the score on a visual analog scale, and the change in creatinine levels over 72 hours from admission. RESULTS: The experimental treatment group demonstrated a greater improvement in patients' global assessment of symptoms scores (AUCbaseline-72 h 3,767 vs 3,457 points; P < .001) and a milder increase in creatinine levels (0.07 vs 0.18 mg/dL; P = .045) than the IV furosemide group. The length of stay was 1 day shorter (4 vs 5 days; P < .001) and the incidence of worsening renal function was lower (25% vs 38%; P = .037) in the experimental treatment group. CONCLUSIONS: In this hypothesis generating study, among patients with ADHF and hepatic dysfunction, concomitant use of IV albumin and furosemide for the first 72 hours resulted in a significant improvement in subjective perception symptoms of decongestion and a milder increase in creatinine levels than IV furosemide alone.

Aged

Surgical management of esophageal atresia with tracheoesophageal fistula in extremely low birth weight neonates: A systematic review.

BACKGROUND: Surgical management of esophageal atresia/tracheoesophageal fistula (EA/TEF) in extremely low birth weight (ELBW) neonates remains challenging and controversial. This study systematically reviews surgical strategies and outcomes in this population. METHODS: Following PRISMA guidelines, Cochrane, Embase, MEDLINE, Scopus, and Web of Science (2004-2024) were searched in February 2025 for studies on surgical management of ELBW neonates with EA/TEF (PROSPERO CRD42025636228). Fatal chromosomal abnormalities were excluded. Demographics, comorbidities, surgical techniques, and complications were analyzed descriptively. Risk of bias was assessed. RESULTS: Eleven publications (five case reports and six case series) comprising 30 patients (Gross type B/C = 1/29) met the eligibility criteria. Mean gestational age was 28.1 (23-34) weeks, and mean birth weight was 760.4 (422-995) g. Twelve primary repairs (PR) and 18 delayed primary repairs (DPR) were performed, including staged repair (n = 11), lower esophageal banding (n = 4), and other techniques (n = 3). Postoperatively, four anastomotic leaks were managed conservatively, six strictures and one recurrent TEF required endoscopic intervention, three fundoplications and two aortopexies were reported (follow-up: 1-198 months, n = 19). Overall mortality was 30% (PR: 8.3%; DPR: 44.4%). Mortality was 60% among neonates with major congenital heart defects (CHD) and 40% among those with VACTERL association. EA/TEF-related complications contributed to 33.3% of deaths. CONCLUSIONS: Mortality in this cohort remains high, particularly with major CHD, and is largely unrelated to EA/TEF-specific complications. In selected cases, PR appears feasible as an alternative to DPR, although conclusions are limited by the small sample size and heterogeneous studies.

Humans

Eating Experiences During Cancer Treatment in Adolescents and Young Adults: A Systematic Literature Review and Meta-Synthesis.

Adolescents and young adults (AYAs) aged 15-39 with cancer face distinct challenges during treatment, with eating consistently emerging as one of the most distressing and underrecognized concerns. At a critical life stage, AYAs must navigate illness-related consequences that profoundly affect well-being. Eating reflects these broader challenges and is identified as a key issue requiring health care attention. To address this, we synthesized evidence on AYAs' eating experiences and well-being during mealtime-related activities to inform health care practice. Qualitative and mixed-method studies were identified through searches across CINAHL, Embase, PubMed, Scopus, and Web of Science for studies published up to May 2025, supplemented by snowball searches. Of 3214 records, 74 full-text articles were reviewed, and 18 met the inclusion criteria. These represented 302 AYAs, 73 relatives, and 88 health care professionals. Studies were analyzed using Joanna Briggs Institute review methods and GRADE-CERQual to support clinical interpretability. The meta-synthesis identified one core theme: "Eating as an embodied struggle and act of agency," with three subthemes: (a) living through physical and sensory disruption, (b) carrying the weight of new emotions and shifting relations, and (c) finding ways through gaps in support. Eating emerged as a disrupted, emotionally charged, yet agentic act requiring sensitive, individualized approaches. Thirteen evidence-informed recommendations were developed to guide clinical application. These emphasize early nutritional screening, dietetic support, flexible meal options, respectful family involvement, and psychosocially attuned care. Future research should codevelop and evaluate tailored interventions that address AYAs' embodied, emotional, and social needs to improve eating-related quality of life during cancer treatment.

Humans

Effect of an oral complementary medicine combination for symptomatic knee osteoarthritis: A double-blind, randomized, placebo-controlled trial.

OBJECTIVE: Many individuals use complementary medicine therapies for osteoarthritis, despite limited scientific supporting evidence. These therapies have demonstrated anti-inflammatory, antioxidative, and chondroprotective effects via different molecular pathways, suggesting potential therapeutic benefits. This trial aimed to evaluate the efficacy and safety of a novel oral complementary medicine combination in adults with symptomatic knee osteoarthritis at 12 weeks. DESIGN: The 12-week, double-blind, randomized, placebo-controlled ATLAS trial was conducted in Australia from July 2024 to April 2025 (ACTRN12623000380695). Eligible participants were aged &#x2265;40 years with symptomatic knee osteoarthritis and radiographic Kellgren-Lawrence grade &#x2265;2. Participants were randomized 1:1 to receive the complementary medicine combination, comprising a total daily dose of Boswellia serrata extract 250&#x202f;mg, pine bark extract 100&#x202f;mg, methylsulfonylmethane 1500&#x202f;mg, curcumin 500&#x202f;mg, and piperine 5&#x202f;mg, or placebo. The primary outcome was the 12-week change in knee pain (0-100&#x202f;mm visual analogue scale (VAS)). A 95% confidence interval excluding differences >18&#x202f;mm between groups was interpreted as the absence of a clinically meaningful difference. Harms were monitored weekly. RESULTS: Eighty-four participants were recruited (mean [SD], age 63.7 [8.0] years, BMI 29.0 [5.5] kg/m2), and 57% were female. At 12-weeks, both groups (intention-to-treat population: complementary medicine, n=42; placebo, n=41) showed a decrease in VAS pain (least squares means: complementary medicine 20.1&#x202f;mm vs placebo 20.3&#x202f;mm), however with no difference between groups: 0.16&#x202f;mm (95% CI -6.81 to 7.12). The safety profile of experiencing any AE was similar between groups (risk difference, -3.4% [95% CI -24.8-17.9%]); and most adverse events were mild or moderate. Four participants experienced serious adverse events, unrelated to the treatment. CONCLUSIONS: The complementary medicine combination was not superior to placebo for improving pain over 12 weeks, and the evidence does not support the use of this combination to treat people with symptomatic knee osteoarthritis.

Humans

Continuous Intravenous Lidocaine for Refractory Cancer Pain in Palliative Care: A Multicenter Feasibility Study.

ObjectivesTo assess the feasibility and tolerability of continuous low-dose intravenous lidocaine infusion in patients with opioid-refractory cancer pain receiving palliative care, and to explore its potential impact on pain outcomes in real-world clinical conditions.MethodsWe conducted a multicenter, randomized, double-blind, placebo-controlled feasibility study in palliative care units to evaluate continuous intravenous lidocaine infusion in patients with opioid-refractory cancer pain. Patients were randomized to receive lidocaine (5&#x2005;mg/kg/day, increased to 8&#x2005;mg/kg/day if pain reduction was <30% after 24&#x2005;h) or placebo for 48&#x2005;h. Pain intensity was assessed using the Numeric Pain Intensity Scale, with a clinically meaningful response defined as a&#x2009;&#x2265;30% reduction from baseline at 40&#x2005;min. Secondary outcomes included pain evolution over time, neuropathic pain, symptom burden, and tolerability.ResultsThirty-five patients were included in the final analysis (18 lidocaine, 17 placebo). No significant difference was observed between lidocaine and placebo for the primary endpoint or for secondary pain outcomes. Reductions in pain intensity were observed in both groups. In the lidocaine group, 61% of patients required dose escalation to 8&#x2005;mg/kg/day. Continuous intravenous lidocaine infusion was generally well tolerated, with mostly mild adverse events and no unexpected toxicity.ConclusionIn this multicenter feasibility study, continuous low-dose intravenous lidocaine did not demonstrate a clinically meaningful analgesic benefit over placebo. As the planned sample size was not reached, the study was underpowered. These findings highlight the challenges of randomized trials in palliative care and may inform future feasibility-oriented designs.

Humans

Updated adjunctive minocycline for schizophrenia: A systematic review and meta-analysis of clinical and cognitive outcomes.

BACKGROUND: Minocycline has been proposed as an adjunctive treatment for schizophrenia due to its anti-inflammatory and neuroprotective properties. However, evidence regarding its efficacy across clinical and cognitive outcomes remains inconsistent. METHODS: A systematic review and meta-analysis of double-blind RCTs was conducted following PRISMA guidelines. PubMed, Web of Science, Embase, Ovid MEDLINE, and the Cochrane Library were searched from January 2000 to August 2025. Eligible studies included patients with schizophrenia receiving adjunctive minocycline plus stable antipsychotics. Primary outcomes were PANSS total and subscale scores and overall cognitive performance. Secondary outcomes included SANS, CDS, CGI, GAF, and seven cognitive domains. Standardized mean differences (SMDs) with 95% CIs were calculated. RESULTS: Ten RCTs involving 895 participants were included. Adjunctive minocycline was associated with improvements in negative symptoms (PANSS negative: SMD = -0.55, 95% CI: -0.96 to -0.13; SANS: SMD = -0.75, 95% CI: -1.00 to -0.49) and overall psychopathology (PANSS total: SMD = -0.49, 95% CI: -0.80 to -0.18). Cognitive benefits were limited to a modest improvement in working memory (SMD = 0.24, 95% CI: 0.08 to 0.39), with no significant effects in other cognitive domains. Subgroup analyses suggested that illness stage, antipsychotic regimen, treatment duration, sample size, and geographic region may contribute to variability in treatment effects. Adverse event rates were comparable between groups. CONCLUSIONS: Adjunctive minocycline may improve negative symptoms and provide modest working memory benefits in schizophrenia. However, the evidence is limited by substantial heterogeneity, potential small-study effects, and inconsistent findings. Although short- to medium-term tolerability appeared comparable to placebo, larger, longer-term RCTs are needed to confirm its efficacy and safety.

Humans

Improving survival in Duchenne muscular dystrophy across eras: a systematic review and cumulative meta-analysis.

BACKGROUND: Duchenne muscular dystrophy (DMD) was historically associated with death in the late teens or early twenties, mainly from respiratory failure. Survival has improved substantially with home mechanical ventilation (HMV) and multidisciplinary care, although variability remains. This study evaluated temporal trends in survival in DMD and the impact of HMV. METHODS: A study-level cumulative meta-analysis (PROSPERO CRD420251163011) of studies reporting survival outcomes in patients with DMD was conducted (PubMed 1977 to 13 October 2025). Pooled estimates of median survival were calculated, and random-effects meta-analyses with predefined subgroups (HMV and study period) were performed, alongside meta-regressions. Risk of bias was assessed using the Newcastle-Ottawa Scale. RESULTS: 53 studies (median follow-up 8&#xa0;years), comprising more than 13,000 patients, of whom 60% received HMV, were included. Median survival differed substantially between ventilated (29&#xa0;years, 95%CI 27 to 31) and non-ventilated (19&#xa0;years, 95%CI 18 to 20) patients. Survival improved progressively over time in both groups. Glucocorticoid therapy was not associated with improved survival (p=0.45), whereas treatment with heart failure medications, including renin-angiotensin system inhibitors (p=0.002) and &#x3b2;-blockers (p=0.02), was associated with longer survival. The predominance of mortality shifted from respiratory to cardiac causes, while enhanced cardiac management was associated with a growing contribution of other causes of death. CONCLUSION: Survival in DMD has increased substantially over time, with median survival now approaching the third decade of life among ventilated patients. The growing contribution of cardiac and other non-respiratory causes of death highlights the importance of long-term multidisciplinary and early cardioprotective intervention. STUDY REGISTRATION: The meta-analysis and systematic review have been registered on PROSPERO (CRD420251163011).

Humans

Estimated prevalence and distribution of causes of immune-mediated hypertrophic pachymeningitis in S&#xe3;o Paulo, Brazil.

BACKGROUND: The prevalence of hypertrophic pachymeningitis (HP) remains poorly defined worldwide. In Japan, the estimated prevalence is 0.949 cases per 100,000 inhabitants, with most cases related to ANCA-associated vasculitis or IgG4-related disease. In contrast, epidemiological data from other regions, including Latin America, are scarce. METHODS: This study was conducted at a tertiary referral center in the city of S&#xe3;o Paulo, Brazil. The prevalence of HP was estimated by comparison with the known prevalence of multiple sclerosis (MS), based on the number of patients with each condition followed at our institution. The etiological distribution of HP was also analyzed. In addition, HP prevalence was compared with that of tuberculous meningoencephalitis, a compulsory notifiable disease and a well-established cause of chronic meningitis in Brazil, using data from the national surveillance system (SINAN). RESULTS: We identified 55 patients with HP: 36 (65%) idiopathic, 10 (18%) IgG4-related disease, 4 (7%) ANCA-associated pachymeningitis, 4 (7%) probable or definite neurosarcoidosis, and 1 (2%) secondary to rheumatoid arthritis. Among 968 registered MS patients and assuming an MS prevalence of 15 per 100,000 inhabitants in S&#xe3;o Paulo, the estimated HP prevalence was 0.85 per 100,000 inhabitants. This estimate was comparable to the prevalence of tuberculous meningoencephalitis in the same region. CONCLUSION: The estimated prevalence of HP in S&#xe3;o Paulo (0.85 per 100,000) is consistent with reports from other regions and is comparable to that of tuberculous meningeal disease, although with a distinct etiological profile. IgG4-related disease was the most frequent systemic association, differing from previous reports. ANCA-associated HP appears to be less frequent than in other geographic regions, possibly reflecting differences in disease phenotype. Key Points &#x2022; The estimated prevalence of HP in S&#xe3;o Paulo was 0.85 per 100,000 inhabitants. &#x2022; IgG4-related disease was the most common systemic disease identified among patients with HP. &#x2022; ANCA-associated HP was less common than reported in Asian and European cohorts. &#x2022; The prevalence of HP was comparable to that of tuberculous meningoencephalitis in S&#xe3;o Paulo.

Humans

ScRNA-seq analysis reveals the effects of nitrite stress on the endocrine system of the eyestalk in Litopenaeus vannamei.

Nitrite is a harmful substance generated in Litopenaeus vannamei farming systems, largely originating from the inadequate breakdown of surplus feed and shrimp feces. Its accumulation in the water can affect the growth and physiological functions of shrimp, damage the immune system, and even cause mass mortality, thus becoming a key environmental factor restricting the green development of the industry. Under nitrite stress, the eyestalk, as an important neuroendocrine regulatory center in crustaceans, participates in the stress adaptation of the organism and exerts a protective effect by regulating energy metabolism and immune function. However, the molecular regulatory mechanism of the eyestalk in response to nitrite stress remains unclear. In this study, single-cell RNA sequencing (scRNA-seq) technology was used to analyze the heterogeneity of eyestalk cells in L. vannamei under nitrite stress. A total of 18, 394 high-quality cells were obtained, and six major cell subpopulations, including Neurosecretory cell, Motor neuron, Sensory neuron, Interneuron, Neurogliocyte, and Support cell, were identified. Differential expression analysis identified 839 differentially expressed genes, and different cell types showed distinct specific responses to nitrite stress. Functional enrichment analysis indicated that pathways such as glycolysis, oxidative phosphorylation, ribosome function, and endoplasmic reticulum protein processing were significantly activated, while signal transduction and DNA repair-related pathways were inhibited. Further analysis revealed that nitrite stress could induce mitochondrial function changes and trigger oxidative stress, thereby affecting the neuroendocrine system function of the eyestalk. This study provided insights into transcriptomic responses of the eyestalk to nitrite stress at the single-cell level, laying a theoretical foundation for the management of aquaculture environments.

Animals

Anabolic androgen therapy in critically ill adults: A systematic review and meta-analysis.

Critical illness is characterized by a catabolic, proinflammatory state. Anabolic agents, such as testosterone, have therefore been proposed as therapeutic targets. Our objectives were to assess the effects of testosterone in critically ill populations on patient-important outcomes and identify design limitations to inform future studies. We searched for randomized control trials (RCTs) through Medline, Embase, and EBM Reviews databases from inception through February 24, 2026, including English language articles enrolling adults (&#x2265;18&#xa0;years) admitted to ICU where anabolic androgen therapies (AAT) were compared with placebo or standard of care. Studies had to report at least one of: mortality, ICU and hospital lengths of stay, or duration of mechanical ventilation. We extracted data independently using a standardized data extraction tool, and feedback was received from all co-authors to ensure agreement. For each outcome, we performed meta-analyses using a random-effects model with inverse variance weighting in RevMan. We used the GRADE approach to assess certainty in pooled estimates of effect. Of 1325 screened articles, we found 4 that fit our inclusion criteria. Together, we judged risk of bias as 'some concerns' in 3 trials and 'high' in the final trial, and ultimately found that the effects of anabolic-androgen therapy on patient-important outcomes uncertain. With the uncertainty of current evidence for the effects of anabolic-androgen therapy in critically ill adults, there is insufficient support for its routine use. Future randomized evidence is needed to determine whether anabolic-androgen therapy improves clinically-important outcomes and better define its safety profile in critically ill adults.

Humans

Catheter ablation for symptomatic atrial fibrillation (PVI-SHAM-AF): a randomised, double-blind, sham-controlled, multicentre trial.

BACKGROUND: Guidelines recommend catheter ablation for symptom relief in patients with atrial fibrillation. The aim of this trial was to ascertain whether catheter ablation improves atrial fibrillation-related quality of life more than a sham procedure. METHODS: PVI-SHAM-AF was a double-blind, multicentre, randomised trial conducted at nine study sites in Germany and Poland. Patients aged 18 years or older with symptomatic paroxysmal or persistent atrial fibrillation were randomly assigned in a 2:1 ratio to catheter ablation or a sham procedure using an automated online randomisation system with variable block sizes, stratified by trial site. The primary endpoint was the between-group difference in change from baseline to 6 months in the Atrial Fibrillation Effect on the Quality-of-life Questionnaire (AFEQT) summary score. The prespecified primary analysis was done in the intention-to-treat population and included all randomly assigned patients, with missing data handled by multiple imputation. This trial is registered with ClinicalTrials.gov (NCT05119231) and 12-month follow-up is ongoing. FINDINGS: Between Nov 12, 2021, and Nov 3, 2025, 1199 patients were invited to participate in the study and 262 patients consented and were randomly assigned: 173 patients to catheter ablation and 89 to sham. The median age was 67 years (IQR 62-73); 134 (51%) were female and 128 (49%) were male. Median follow-up was 184 days (IQR 181-191). At 6 months, the mean AFEQT summary score had increased from 61&#xb7;3 (SD 20&#xb7;1) to 81&#xb7;1 (16&#xb7;6) in the catheter ablation group and from 59&#xb7;2 (19&#xb7;0) to 74&#xb7;9 (19&#xb7;5) in the sham control group. The Hodges-Lehmann estimate of the between-group difference in change was 2&#xb7;6 (95% CI -2&#xb7;7 to 8&#xb7;0; p=0&#xb7;36). One death occurred in each group; neither was considered related to the study procedure. Serious adverse events adjudicated as related or possibly related to the study procedure occurred in ten unique patients: six patients in the catheter ablation group and four patients in the sham control group. One of these was an ischaemic stroke occurred in the sham control group. INTERPRETATION: Catheter ablation did not demonstrate superiority over a sham procedure for improving atrial fibrillation-related quality of life at 6 months. FUNDING: Helios Gesundheit (F&#xf6;rderung Leipziger Herzmedizin).

Humans

Oral semaglutide for weight loss and liver fibrosis in overweight and obesity: A randomized controlled trial.

BACKGROUND AND OBJECTIVES: Obesity is a leading risk factor for fatty liver disease and weight loss has been shown to improve liver parameters. This study evaluates the efficacy of oral semaglutide for weight loss in individuals with overweight or obesity, excluding those with diabetes mellitus. METHODS: A randomized, open-label, controlled trial was conducted at the Asian Institute of Gastroenterology, Hyderabad, from June 2022 to December 2023. Adults (&#x2265;&#x2009;18&#xa0;years) with a body mass index (BMI)&#x2009;&#x2265;&#x2009;30 or&#x2009;&#x2265;&#x2009;27 with comorbidities (pre-diabetes, hypertension, dyslipidemia, obstructive sleep apnea or cardiovascular disease) were randomized into two groups. Both groups received counselling on a reduced-calorie diet and increased physical activity. Group 1 also received oral semaglutide, starting at 3&#xa0;mg/day and titrated to 14&#xa0;mg/day over two to four&#xa0;weeks. The objectives were to assess the effects of semaglutide on weight loss, non-invasive markers of liver fibrosis and cardiometabolic parameters. (ClinicalTrials.gov ID: NCT05442450). RESULTS: Total 116 participants (58 per group) completed the study. At 28&#xa0;weeks, the mean percentage weight reduction was -10.47% (SD 5.3) in the Semaglutide group vs. -2.4% (SD 4.5) in the control group (p&#x2009;<&#x2009;0.001). Semaglutide treatment significantly improved alanine aminotransferase (ALT) (serum glutamic-pyruvic transaminase [SGPT]) levels, along with reductions in the aspartate aminotransferase to platelet ratio index (APRI) score, liver fat content and liver stiffness. However, NFS (NAFLD fibrosis score) and FIB-4 (fibrosis-4 index) did not show significant reductions. Improvements in BMI, waist circumference, HbA1c, fasting insulin and C-reactive protein (CRP) were significantly greater with semaglutide (p&#x2009;<&#x2009;0.001). Total fat mass decreased by 7.3&#xa0;kg vs. 1.74&#xa0;kg (p&#x2009;<&#x2009;0.0001) in controls, while visceral fat ratings dropped by 3.67 vs. 0.6 (p&#x2009;<&#x2009;0.0001). CONCLUSIONS: In adults with overweight or obesity without diabetes, oral semaglutide, combined with dietary and lifestyle modifications, led to significant and clinically meaningful weight loss and metabolic improvements compared to lifestyle modifications alone.

Adult

Assessing perinatal depression identifying abilities among maternal and child health workers in rural China using smartphone-based virtual patients: a multi-center cross-sectional study.

OBJECTIVE: To assess rural maternal and child health (MCH) workers' virtual patients (VPs)-assessed performance in identifying perinatal depression (PND) using smartphone-based VPs, and to identify factors associated with this performance in rural Hunan, China. METHODS: A multicentre cross-sectional study was conducted in Hunan Province, China. A standardized questionnaire collected demographic and work-related characteristics of rural MCH workers. Smartphone-based VPs were used to assess PND identification performance in a simulated clinical scenario. An overall score &#x2265;60 was used as a prespecified operational benchmark across consultation, ancillary assessment, diagnosis, management, and health education domains. Data were analyzed using SPSS 26.0. RESULTS: A total of 375 rural MCH workers participated, yielding an effective response rate of 90.4%. Only 25.9% met the prespecified operational benchmark for VP-assessed PND identification performance. The mean accuracy scores for consultation, ancillary assessment, diagnosis, management, and health education were 94%, 48%, 64%, 58%, and 74%, respectively. Complete consultation accuracy was higher among MCH workers from township health centers than among those from county-level MCH hospitals. MCH workers aged 18-39 years showed higher odds of complete diagnostic accuracy for PND than those aged &#x2265;40 years. CONCLUSIONS: Smartphone-based VP assessment was feasible in rural MCH settings and revealed suboptimal PND identification performance. Mobile VPs may help identify frontline performance gaps and inform targeted training, but further validation against real-world clinical performance, or standardized patient encounters is needed before large-scale implementation. These findings may support targeted capacity-building for rural MCH workers and more equitable perinatal mental health care.

Humans