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PubMed2026

Contrast Heat-Cold Versus Thermoneutral Showering in Trained Combat Sport Athletes: A Randomized Field Trial of Recovery Outcomes.

Contrast heat-cold showering is popular for recovery, but multisystem evidence and persistence after cessation remain unclear. To evaluate whether a 4-week post-training contrast heat-cold shower intervention produces an integrated recovery profile across four domains (autonomic, endocrine, perceptual, and microvascular) rather than testing a single isolated physiological pathway, across baseline (T0), post-intervention (T1), and 2-week wash-out (T2). Sixty combat-sport athletes were randomized to contrast showers (10 min alternating warm 38-40°C and cold 13-15°C) or an active thermoneutral-shower comparator (10 min, 32-34°C) after training for 4 weeks. Primary analyses were per-protocol (≥ 75% compliance; n = 57), with intention-to-treat sensitivity analyses. Outcomes were Total Quality Recovery (TQR), morning salivary cortisol (two mornings averaged), resting HRV, and post-occlusive reactive hyperemia (PORH). From T0 to T1, favorable between-group changes were observed for resting HR (ΔΔ -2.10 bpm, 95% CI -2.24 to -1.96; g -0.65; p < 0.001), lnRMSSD (ΔΔ 0.123 log units, 95% CI 0.108 to 0.137; g 0.74; p < 0.001), with similar T1 effects for RMSSD and SDNN, and TQR (ΔΔ 0.61 points, 95% CI 0.27 to 0.95; g 0.80; p < 0.001). These T1 autonomic and perceptual changes were not maintained at T2 (all T2-T0 ΔΔ p > 0.05). Cortisol and PORH-derived outcomes showed no statistically clear between-group differences at T1 or T2 (all p > 0.05). Compared with thermoneutral showering, 4 weeks of post-training contrast heat-cold showering produced short-term favorable between-group changes in autonomic regulation and perceived recovery, but not in morning cortisol or PORH-derived microvascular reactivity. These effects were not maintained after wash-out; therefore, causal attribution to the shower intervention alone and claims of persistent physiological adaptation should be made cautiously. Trial registration: ISRCTN15418049.

Humans↗

PubMed2026

Predictors of Treatment Failure in Children With HIV Starting First-line Antiretroviral Therapy in the ODYSSEY Trial.

BACKGROUND: Data on predictors of treatment failure in children starting antiretroviral therapy (ART) are limited, particularly on dolutegravir-based regimens (DTG). METHODS: ODYSSEY demonstrated superior efficacy of DTG versus standard-of-care (SOC). We assessed predictors at ART initiation of treatment failure by 96 weeks. RESULTS: Three hundred and eighty-one children started first-line ART (82% African). At ART-initiation, median age was 10.5 years (IQR: 6.5, 14.0, 67 < 3 years), CD4% 20% (IQR: 12, 28), BMI-for-age Z-score -.58 (IQR:-1.48, +.25). One hundred and eighty-nine children started DTG, 192 started SOC (91% ≥3 years started efavirenz; 79% <3 years started lopinavir). Seventy-five children experienced treatment failure (24 DTG, 51 SOC). Failure risk was lower on DTG than SOC (hazard ratio [HR] = 0.47, 95% CI: 0.29-0.77, P = .002). Lower BMI-for-age Z-score (HR = 0.82 for each unit gain, 95% CI: 0.70-0.96, P = .01) and being at an African site (HR = 2.09, 95% CI: 0.82-5.31, P = .09) were associated with higher failure risk. Risk was also higher at younger ages with the steepest increase in the youngest children and increased at lower CD4%, with a stronger CD4% effect at younger ages. At CD4% = 20, HRs relative to age 10 years were 2.40 (95% CI: 1.58-3.65) at age 1 year, 1.30 (95% CI: 1.15-1.48) at age 5 years, and 0.80 (95% CI: 0.72-0.89) at age 18 years. At age 1 year, HRs relative to CD4% = 20 were 1.39 (95% CI: 1.16-1.66) at CD4% = 15, and 0.52 (95% CI: 0.36-0.75) at CD4% = 30; at age 10, corresponding estimates were 1.07 (95% CI: 0.94-1.20) at CD4% = 15, and 0.88 (95% CI: 0.69-1.13) at CD4% = 30. CONCLUSIONS: Young age, low BMI-for-age, and low CD4% at ART initiation predicted higher risk of treatment failure and can guide targeted support.

Humans↗

PubMed2026

CL16019, A Combination of Cissus quadrangularis and Boswellia serrata Extracts Promotes the Healing of Distal Radius Fractures: A Multicentric, Randomized, Open-Label Study.

OBJECTIVE: Distal radius fracture (DRF) is the most frequent injury to the upper limb. Complications include nonunion, wrist stiffness and instability, local discomfort, and tendon irritation. The purpose of the current open-label clinical study was to evaluate the safety, efficacy, and tolerability of CL16019, an herbal formulation of Cissus quadrangularis and Boswellia serrata extract, in accelerating fracture healing in volunteers with DRFs. METHODS: Fifty participants (both male and female; age: 30-50 years) with type I, IIA, or IIB DRFs (as per Lidstrom classification) were equally randomized and treated with standard treatment (ST) or ST + CL16019 for 60 days. The primary efficacy outcome was the radiographical bone fracture healing rate as scored by the Radius Union Scoring System (RUSS). Pain, swelling, and tenderness were among the clinical characteristics evaluated using the visual analog scale (VAS). Wrist function improvements were assessed using the Patient-Rated Wrist Evaluation Questionnaire (PRWEQ). The intergroup and intragroup results were analyzed using a paired t-test and an analysis of covariance model, respectively. RESULTS: The RUSS scores for the ST and ST + CL16019 groups at the end of the trial were 5.54 ± 1.77 and 7.96 ± 0.20, respectively, with a p-value <0.0001. In addition, the CL16019 volunteers showed substantial (p < 0.05) declines in their VAS and PRWEQ scores. The ST + CL16019 group demonstrated higher Physician Global Assessment and Subject Global Assessment scores. CONCLUSIONS: Supplementation of CL16019 along with standard therapy was found to enhance the bone fracture healing rate, possibly by accelerating the callus formation rate and enhancing cortical bridging. These findings imply that CL16019 might be a good adjunctive in addition to ST for the faster healing of DRFs. The trial was registered with the Clinical Trial Registry of India (CTRI) with the registration number CTRI/2021/12/039006, on December 29, 2021.

Humans↗

PubMed2026

GIP contributes to postprandial regulation of splanchnic blood supply in humans with type 2 diabetes: a randomised, single-blinded, placebo-controlled, crossover study.

AIMS/HYPOTHESIS: In healthy lean humans, endogenous glucose-dependent insulinotropic polypeptide (GIP) contributes significantly to the postprandial increase in arteria mesenterica superior blood flow. The vascular biology related to activation of the GIP receptor is markedly impaired in individuals with type 2 diabetes and is sometimes absent. In this population, we investigated the role of endogenous GIP on postprandial splanchnic blood flow by using the GIP receptor antagonist, GIP(3-30)NH2. The primary outcome of this study was the changes in blood flow in arteria mesenterica superior during oral glucose with or without GIP receptor antagonist infusion. METHODS: Ten participants with type 2 diabetes (age 20-80 years, BMI 20-35 kg/m2, and HbA1c >48 mmol/mol and <75 mmol/mol) were investigated in a randomised, placebo-controlled, crossover study. On four separate occasions, participants received the following treatment: oral glucose + i.v. GIP(3-30)NH2; oral glucose + i.v. saline (154 mmol/l NaCl); oral water + i.v. GIP(3-30)NH2; oral water + i.v. saline. Participants were randomly assigned to intervention groups using (random.org). Participants were unaware of allocation, while investigators were aware. No additional allocation concealment procedures were used. During all four interventions, splanchnic blood flow was measured using phase-contrast MRI in the arteria mesenterica superior, truncus coeliacus and vena portae during oral glucose (75 g) or water ingestion. The study was conducted at Rigshospitalet, Copenhagen. Liver volume and oxygenation, as well as gallbladder volume, were assessed. Blood samples were collected and analysed for insulin, C-peptide, GIP, glucagon and glucose. RESULTS: Oral glucose alone increased mean blood flow in arteria mesenterica superior by 57% (95% CI 26, 88) and this was 15% (95% CI -2, 32) lower during concomitant GIP receptor antagonist infusion, p=0.012. Infusion of GIP receptor antagonist during oral glucose treatment did also result in lower insulin secretion, C-peptide and C-peptide/glucose ratio compared with saline infusion, whereas glucagon levels and plasma glucose were unaffected. Oral water did not affect any outcomes. CONCLUSIONS/INTERPRETATION: Endogenous GIP contributes to postprandially increased splanchnic blood flow in people with type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT06426823 FUNDING: This work was supported by the Novo Nordisk Foundation.

Humans↗

PubMed2026

Treatment-related associations of nucleus accumbens connectivity within mesocorticolimbic circuits in depression.

Pharmacological treatment remains a mainstay in managing depression, yet the neural correlates associated with treatment response remain incompletely understood. This study used multimodal neuroimaging to examine nucleus accumbens (NAc)-centered structural and functional alterations associated with fluoxetine and Shugan Jieyu Capsule (SG), a traditional Chinese medicine, in patients with mild-to-moderate depression (MMD). Sixty patients were randomized to an 8-week course of fluoxetine or SG. Depression severity was assessed using the 24-item Hamilton Depression Rating Scale (HAMD-24), and structural and functional MRI scans were acquired at baseline and endpoint. Both treatments were associated with significant symptom improvement. Neuroimaging analyses revealed structural and functional alterations involving the NAc. Changes in NAc-amygdala connectivity showed an exploratory association with symptom improvement in the SG group, whereas changes in NAc-rostral anterior cingulate cortex connectivity were associated with symptom improvement in the fluoxetine group and remained significant after correction for multiple comparisons. In addition, remitters exhibited stronger baseline connectivity between the NAc and ventral tegmental area and between the NAc and middle frontal gyrus compared with non-remitters. These findings suggest that NAc-centered connectivity may be relevant to treatment-related neural changes in depression and may inform future research on imaging-based candidate markers of treatment response and personalized treatment approaches. TRIAL REGISTRATION: The study is registered in https://www.chictr.org.cn/ with a registration number ChiCTR1900024988 (date: 08.06.2019).

Humans↗

PubMed2026

Virtual reality physical education and adolescents' exercise interest and physical fitness: An explanatory sequential mixed-methods randomized trial with exploratory pathway analysis.

Traditional physical education (PE) faces declining student interest and limited fitness gains. Virtual reality (VR) offers immersive, gamified experiences, but evidence regarding its effectiveness and explanatory pathways remains limited. This explanatory sequential mixed-methods randomized trial assigned 360 adolescents (aged 13-16) from three middle schools to either VR-supported PE (n = 180) or conventional PE (n = 180) for 12 weeks, with a 4-week follow-up. Outcomes included exercise interest (validated scale), physical fitness (coordination via MABC-2, cardiorespiratory endurance via the 20-m shuttle run, explosive power via the standing long jump, and speed via the 10-m sprint), and accelerometer-measured physical activity. The qualitative component involved 38 unique students: 32 completed individual semi-structured interviews, and six additional students participated only in focus groups. Three-level linear mixed-effects models and exploratory structural equation modeling were used. The VR group showed significantly greater improvements in exercise interest (d = 0.78), coordination (d = 0.62), cardiorespiratory endurance (d = 0.55), and speed (d = 0.48) than the control group (all p < 0.001), but not in explosive power (d = 0.12, p = 0.148). Effects were partially retained at follow-up (interest d = 0.65, coordination d = 0.48, endurance d = 0.42, and speed d = 0.30), a pattern not fully consistent with a purely novelty-driven explanation. Exploratory mediation identified exercise interest as a statistically compatible explanatory pathway (indirect effect = 0.34, 95% CI [0.22, 0.46]), although the timing of measurement precludes causal interpretation. Qualitative findings contextualized these results by highlighting immersion, feedback, self-efficacy, and perceived transfer. VR-supported PE may enhance adolescents' exercise interest and selected fitness dimensions, but its limited effect on explosive power and possible novelty contribution indicate that it should complement, rather than replace, conventional PE. Longer-term studies are needed.

Humans↗

PubMed2026

Acute mild cold exposure with shivering reduces 24 h glucose levels in individuals with type 2 diabetes but not prediabetes.

AIMS/HYPOTHESIS: Repeated cold exposure with shivering has been proposed as a potential strategy to enhance glucose metabolism by increasing energy expenditure and substrate utilisation. However, acute effects/benefits of cold-induced shivering on glucose homeostasis in metabolically compromised individuals are unknown. Here, we aimed to determine whether cold exposure at two different intensities improves 24 h glucose homeostasis in individuals with prediabetes and type 2 diabetes. METHODS: In a randomised crossover trial conducted in the South Limburg/Maastricht region of the Netherlands, men and postmenopausal women with prediabetes (n=12) and stable type 2 diabetes (n=12), aged 40-75 years, body mass index ≥27 and ≤35 kg/m2, non-smoking and sedentary, underwent two whole-body cold exposure sessions using a water-perfused suit. Session order was randomised using an online randomisation tool (randomizer.org); participants were masked to the cold exposure intensity received, but investigators were not. Sessions were designed to elicit ~1.5-fold (mild, 15°C) and ~2.5-fold (moderate, 4°C) increases in resting metabolic rate (RMR). Continuous glucose monitoring assessed interstitial glucose concentrations over 24 h periods before and after each intervention, with controlled diet and activity. Shivering was confirmed via indirect calorimetry and electromyography. RESULTS: In both study groups and periods, RMR increased significantly vs baseline (p<0.001 for all). In prediabetes, the increase in the final 1 h of cold was 1.53 × RMR in mild and 1.94 × RMR in moderate cold. In type 2 diabetes, the increase was 1.57 × RMR and 2.09 × RMR in the final 1 h of mild and moderate cold, respectively. In prediabetes, neither mild nor moderate cold exposure altered mean 24 h glucose levels. In contrast, after mild cold exposure the type 2 diabetes group exhibited a significant reduction in mean 24 h glucose levels (-0.6 ± 0.5 mmol/l, p=0.003) and fasting glucose (-0.6 ± 0.8 mmol/l, p=0.019), as well as an increase in time in normal range (+8.8 ± 10.3%, p=0.013) and reduced time in hyperglycaemia (-10.9 ± 12.9%, p=0.014). Moderate cold did not significantly affect any of the glucose outcomes in type 2 diabetes. Baseline fasting glucose, age and ALT levels were predictors of the glucose-lowering response, suggesting greater benefits in individuals who have higher baseline glucose levels, are younger and/or have more optimal liver health, i.e. lower ALT. CONCLUSIONS/INTERPRETATION: Acute mild cold exposure with shivering reduced 24 h glucose levels in individuals with type 2 diabetes. No changes were observed in prediabetes. The observed effects appear to depend on baseline metabolic status rather than acute substrate utilisation during cold exposure. These findings support the potential of cold exposure as an adjunct non-pharmacological therapy for type 2 diabetes, although further mechanistic studies and validation in larger cohorts are warranted. TRIAL REGISTRATION: ClinicalTrials.gov NCT05576025 FUNDING: Dutch Organisation for Knowledge and Innovation in Health, Healthcare and Well-being (ZonMw): 09120012010062.

Humans↗

PubMed2026

AI echo INSIGHT study: A prospective blinded randomized trial of artificial intelligence echocardiogram interpretation.

BACKGROUND: Transthoracic echocardiography (TTE) is the most commonly performed cardiac imaging modality with over 30 million studies annually. Demand for timely expert interpretation continues to outpace capacity, creating diagnostic delays and inter-observer variability that impact patient care. Recent research has suggested computer vision artificial intelligence (AI) models can generate accurate preliminary comprehensive TTE reports, however, prospective evaluation is needed to determine whether AI-assisted TTE interpretation can improve clinician efficiency while preserving diagnostic accuracy. METHODS: AI ECHO INSIGHT is a prospective randomized blinded clinical trial conducted at Kaiser Permanente Northern California that will evaluate 1200 historical TTE studies (1000 consecutive unselected studies plus 200 with moderate or greater valvular disease) interpreted using three workflows: (1) AI-generated preliminary report finalized by a blinded cardiologist (AI-assisted); (2) cardiologist-generated preliminary report finalized by a blinded cardiologist (cardiologist-assisted); and (3) sonographer-generated preliminary report finalized by a blinded cardiologist (sonographer-assisted). The primary outcome is the rate of substantial change between preliminary and final reports, comparing the AI-assisted workflow to the pooled cardiologist-assisted and sonographer-assisted workflows. Secondary outcomes include cardiologist interpretation time for report finalization, superiority testing for diagnostic accuracy, and reporting consistency. CONCLUSION: AI ECHO INSIGHT is a prospective randomized blinded clinical trial evaluating the clinical impact of AI-assisted TTE interpretation on diagnostic accuracy, cardiologist efficiency, and reporting consistency in real-world echocardiography workflows. TRIAL REGISTRATION: ClinicalTrials.gov registration number NCT07229300.

Humans↗

PubMed2026

Antibiotic-impregnated bone graft to prevent infection after total hip arthroplasty (ABOGRAFT): protocol for a randomised, double-blind, placebo-controlled trial.

INTRODUCTION: Studies have shown promising results using bone graft as a carrier for local administration of antibiotics to reduce the risk of prosthetic joint infection (PJI). The objective of this clinical trial is to determine if tobramycin and vancomycin-impregnated bone graft is safe and effective in reducing the rate of PJI after total hip arthroplasty (THA). METHODS AND ANALYSIS: This study is an international, randomised, double-blinded, placebo-controlled clinical drug trial. Patients scheduled for THA (n=1100) requiring bone grafting (excluding revisions due to an ongoing infection) are randomised in a 1:1 ratio to prophylactic treatment with tobramycin and vancomycin or placebo-impregnated bone graft.The primary outcome is the time to reoperation due to infection or diagnosis of PJI, expressed as a relative risk difference between the two groups. A risk reduction of at least 50% is considered clinically relevant. Secondary outcomes are time to and reason for reoperation and implant revision, type of micro-organism and antibiotic susceptibility pattern within 2 and 5 years after surgery. Safety outcomes are the number of adverse events and revision rate due to aseptic loosening. The primary analysis will be performed using proportional hazard models. ETHICS AND DISSEMINATION: The study has been approved under the Clinical Trial Regulation No 536/2014 (EU CT; 2024-510921-25-00). Results will be published in open-access peer-reviewed journals and disseminated to patient organisations and the media, and de-identified individual participant data will be curated and shared on reasonable request in accordance with the Findability, Accessibility, Interoperability and Reuse principles, subject to the laws and regulations governing data protection in each participating country. TRIAL REGISTRATION NUMBER: NCT05169229.

Humans↗

PubMed2026

Comparison of clinical efficacy and gut microbiota characteristics in children with ASD treated with fecal microbiota transplantation and ketogenic diet.

OBJECTIVE: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social communication and interaction, along with restricted, repetitive patterns of behavior. It is often accompanied by gastrointestinal dysfunction and gut microbiota dysbiosis. Fecal Microbiota Transplantation (FMT) and the Ketogenic Diet (KD) are interventions targeting the gut microbiota for ASD. METHODS: 30 participants were diagnosed with ASD according to DSM-5 and ADOS-2. ASD core symptoms were evaluated with CARS and ABC. Gut microbiota composition was analyzed by shotgun metagenomic sequencing. RESULTS: Both groups demonstrated significant improvements in core symptoms. In the FMT group, the mean CARS score significantly decreased from 34.87 to 33.53 (p < 0.01); in the KD group, it declined from 35.13 to 33 (p < 0.01). The mean ABC score reduced from 79.93 to 69.33 (p = 0.064) in the FMT group and from 63.07 to 42.73 (p < 0.01) in the KD group. Following the intervention, no statistically significant changes were observed in α-diversity or β-diversity within either group. LEfSe analysis revealed distinct post-intervention microbial signatures: FMT significantly enriched butyrate-producing taxa (Wujia chipingensis, Eubacterium sp. MSJ-33, and Butyrivibrio crossotus), while KD elevated Blautia massiliensis and decreased propionate metabolism -associated taxa (Veillonella sp. S12025-13 and Veillonella nakazawae). KEGG enrichment analysis revealed that KD enriched propionate metabolism (Fold enrichment = 3.747, q = 0.010) and aromatic compound degradation (Fold enrichment = 3.591, q = 0.010). CONCLUSIONS: Both interventions significantly improved clinical symptoms among children with ASD, potentially through distinct patterns of gut microbiota modulation. CLINICAL TRIALS NUMBER: NCT06348433 (03/21/2024).

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PubMed2026

Risk factors for leg wound infection after conventional and no-touch vein harvesting: insights from a multicentre randomised trial.

ClinicalTrials.gov: ID NCT03501303.

Humans↗

PubMed2026

Ameliorating Effects and Autonomic Mechanisms of Transcutaneous Auricular Vagus Nerve Stimulation on Abdominal Pain in Patients With Functional Dyspepsia and Irritable Bowel Syndrome.

BACKGROUND: Patients with functional dyspepsia (FD) and irritable bowel syndrome (IBS) often experience abdominal pain and reduced quality of life and need effective treatments. This exploratory study aimed to evaluate whether transcutaneous auricular vagus nerve stimulation (taVNS) could improve abdominal pain and quality of life in patients with FD and IBS, and whether the effects were mediated via the autonomic mechanisms. METHODS: A total of 64 patients with abdominal pain (43 FD and 21 IBS) with a pain score of 3 out of 10 or higher were randomized to receive 2 weeks of taVNS or sham-taVNS treatment. The primary outcome was numeric rating scale (NRS) for abdominal pain. The dyspeptic symptom scales (DSS), IBS symptom severity scale score (IBS-SSS), anxiety and depression scores, and the SF36 quality of life scale were assessed before and after the treatment. The electrocardiogram was also recorded for the assessment of autonomic function at baseline and after the treatment. KEY RESULTS: (1) taVNS reduced the abdominal pain score (p < 0.001 for both FD and IBS), the frequency of abdominal pain (p < 0.001 for both FD and IBS), and overall symptom scores in both FD patients and IBS patients (p < 0.001 for FD and IBS). There was no significant difference in the effect of taVNS on abdominal pain between FD and IBS patients. (2) taVNS improved quality of life compared with baseline in both FD and IBS patients. (3) taVNS decreased anxiety (p < 0.001) and depression (p < 0.001). (4) taVNS increased vagal activity. At the end of the taVNS treatment, the vagal activity was negatively correlated with the pain score (r = -0.491, p = 0.004). CONCLUSIONS: Non-invasive taVNS improves abdominal pain, quality of life, and anxiety and depression in patients with FD and patients with IBS, possibly attributed to the enhancement of vagal activity. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR2400085697.

Humans↗

PubMed2026

Effect of Baseline ASPECTS on Tenecteplase Efficacy Before Thrombectomy in Acute Large-Vessel Occlusion Stroke: A Post Hoc Analysis of the BRIDGE-TNK Randomized Trial.

BACKGROUND AND OBJECTIVES: The impact of ischemic extent on the efficacy and safety of intravenous thrombolysis before thrombectomy remains uncertain. The aim of this study was to evaluate whether the baseline ischemic extent, measured by the Alberta Stroke Program Early Computed Tomography Score (ASPECTS), modifies outcomes of intravenous tenecteplase administered before endovascular thrombectomy. METHODS: This was a post hoc analysis of the BRIDGE-TNK (thrombectomy with vs without rhTNK-tPA in stroke) trial, conducted across China from May 2022 to September 2024. We compared the efficacy and safety of intravenous tenecteplase plus thrombectomy vs thrombectomy alone in acute large-vessel occlusion stroke patients within 4.5 hours of last known well, stratified by baseline ASPECTS (<8 vs 8-10). The outcomes included 90-day functional independence (modified Rankin Scale score of 0-2), 48-hour symptomatic intracranial hemorrhage (sICH), and 90-day mortality. Regression models incorporating a treatment-by-ASPECTS interaction term were used for analysis. RESULTS: Among 550 patients, 241 (43.8%) had ASPECTS <8 (median [interquartile range, IQR] age, 69 [61-77] years; 56.4% male) and 309 had ASPECTS 8-10 (median [IQR] age, 70 [61-77] years; 59.5% male). The rate of functional independence was significantly higher in the tenecteplase plus thrombectomy group than in the thrombectomy-alone group in the ASPECTS <8 subgroup (adjusted risk ratio [aRR], 1.67; 95% CI 1.18-2.35), but not in the ASPECTS 8-10 subgroup (aRR, 0.99; 95% CI 0.84-1.17; pinteraction = 0.007). Rates of sICH did not differ significantly between treatment groups in either ASPECTS subgroups (ASPECTS <8: 10.0% vs 11.2%; ASPECTS 8-10: 7.5% vs 2.8%; pinteraction = 0.11). Ninety-day mortality was comparable between treatment groups in the ASPECTS <8 subgroup, but numerically higher with tenecteplase plus thrombectomy in the ASPECTS 8-10 subgroup (aRR = 1.89, 95% CI 0.99-3.61, pinteraction = 0.04). DISCUSSION: In this exploratory post hoc analysis, a signal of benefit was observed in patients with ASPECTS <8 who received intravenous tenecteplase before thrombectomy, whereas no functional improvement and possible safety concerns were seen in those with ASPECTS 8-10. Prospective confirmation in randomized trials is required before practice change. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov; Unique identifier: NCT04733742.

Humans↗

PubMed2026

Matching-adjusted indirect comparison of fruquintinib versus ramucirumab in advanced gastric or gastroesophageal junction adenocarcinoma.

Aim: Fruquintinib (Fruq), a selective VEGFR 1/2/3 inhibitor, showed a significant progression-free survival (PFS) benefit in the Phase III FRUTIGA trial for advanced gastric/gastroesophageal junction (G/GEJ) adenocarcinoma. Ramucirumab (RAM), an anti-VEGFR2 antibody, demonstrated efficacy in the RAINBOW-Asia trial. This anchored matching-adjusted indirect comparison (MAIC) evaluated Fruq plus paclitaxel versus RAM plus paclitaxel as second-line therapy for G/GEJ adenocarcinoma in the absence of head-to-head trials. Materials & methods: Data from individual patients in the FRUTIGA study (N = 703) and aggregated data from the RAINBOW-Asia study (N = 440) were analyzed. Baseline characteristics were balanced using entropy balancing. The placebo plus paclitaxel (PBO + PTX) groups served as the common comparators. The primary outcome was PFS; secondary outcomes included overall survival, objective response rate (ORR) and disease control rate (DCR). Rates of treatment-emergent adverse events (TEAEs) were also compared as an exploratory outcome using an adjusted indirect risk difference. Sensitivity analyses included restricted mean survival time and simulated treatment comparison. Results: After weighting (effective sample size = 564), baseline covariates were balanced. The anchored MAIC demonstrated that Fruq + PTX significantly improved PFS compared with RAM + PTX (HR: 0.70; 95% CI: 0.51-0.96; p = 0.0280), corresponding to a 30% reduction in progression risk, with a significant restricted mean survival time benefit of 1.18 months at 20 months (95% CI: 0.08-2.27; p = 0.024). Fruq achieved significantly higher ORR (OR: 1.76, 95% CI: 1.16-2.68; p = 0.008) and DCR (OR: 1.94, 95% CI: 1.33-2.83; p < 0.001). Overall survival was similar (0.97; 95% CI: 0.73-1.30; p = 0.8640). Subgroup analyses showed PFS benefits with Fruq in patients with ECOG PS 1, peritoneal metastases and two or fewer metastatic sites. In sensitivity analysis, the simulated treatment comparison also suggested a PFS benefit for Fruq + PTX (HR: 0.40, 95% CI: 0.32-0.50; p < 0.0001). For any-grade TEAEs, the indirect comparison showed higher adjusted relative incidences of increased bilirubin with Fruq + PTX than with RAM + PTX (RD: 12.3%; 95% CI: 2.3-22.4%, p < 0.05) and of hypokalemia (RD: 9.0%; 95% CI: 1.5-16.4%, p < 0.05). For grade ≥3 TEAEs, the adjusted relative incidence of decreased body weight was higher with Fruq + PTX than with RAM + PTX (RD: 2.9%; 95% CI: 0.6-5.2%, p < 0.05). The adjusted relative incidences of increased AST, ALT and hypocalcemia were numerically lower in the fruquintinib group than in the RAM group. Conclusion: This MAIC indicates that Fruq + PTX may be more effective than RAM + PTX in second-line advanced G/GEJ adenocarcinoma, with potentially improved PFS, ORR and DCR, and similar overall survival. Safety analyses suggested generally comparable safety profiles across the two regimens. Fruq + PTX remains a valuable treatment option, offering important comparative evidence for clinical and health technology assessment decisions. Trial Registration: Clinicaltrials.gov identifiers: NCT07144995.

Adult↗

PubMed2026

Implementing Prolonged Exposure Therapy in a Community Substance Use Treatment Program: A Qualitative Study.

INTRODUCTION: Post-traumatic stress disorder (PTSD) commonly co-occurs with substance use disorders (SUD), yet few community-based SUD programs incorporate evidence-based trauma-focused. Prolonged exposure (PE), including its massed format (M-PE) with session frequency of 3-4 times per week, is a gold standard intervention for PTSD; however, concerns about client readiness, logistical demands and relapse risk have limited its adoption within SUD settings. This study examined staff perspectives on the feasibility and acceptability of integrating M-PE into a community-based SUD program. METHODS: Prior to launching a Hybrid Type 1 effectiveness-implementation trial (Project COMET), we conducted semi-structured virtual interviews with 15 community clinic staff: providers (n = 8), administrators (n = 2) and peer specialists (n = 5). Interviews were recorded, transcribed and analysed using a rapid qualitative analysis framework with matrix techniques to compare themes across roles. RESULTS: Four overarching themes captured staff perspectives on integrating M-PE: (Theme 1) Prior Knowledge and Experiences: Most staff were familiar with EMDR, while direct knowledge of PE/M-PE was limited. (Theme 2) Perceptions of M-PE: M-PE was widely viewed as a promising, structured intervention that fits the pacing and duration of SUD care. (Theme 3) Symptom Reduction and Client Impact: Staff anticipated improvements in PTSD and SUD symptoms through trauma-focused treatment. (Theme 4) Barriers and Constraints: Participants identified several potential implementation challenges, including logistical barriers and client readiness. DISCUSSION AND CONCLUSIONS: Findings suggest that staff generally viewed M-PE favourably but emphasised the importance of ensuring client readiness and organisational support. Enhancing feasibility and long-term sustainability may require expanded psychoeducation, targeted provider training and flexible delivery models. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT06968832.

Adult↗

PubMed2026

Naltrexone Is Superior to Placebo for Abstinence and Craving Reduction in Alcohol-Associated Cirrhosis: NAL-CI Trial.

BACKGROUND AND AIMS: Alcohol use disorder (AUD) coexisting with cirrhosis carries high morbidity and mortality, with no approved pharmacotherapy for AUD. We evaluated the safety and efficacy of naltrexone, an opioid receptor antagonist, in patients with compensated alcohol-associated cirrhosis (AaC) and AUD. METHODS: One hundred patients with compensated AaC and DSM-5 AUD were randomised 1:1 to naltrexone (50 mg/day) or placebo for 12 weeks. The primary endpoint was point-prevalence abstinence at 12 weeks, defined as no alcohol use in the four preceding weeks. Secondary endpoints included craving (Obsessive Compulsive Drinking Scale [OCDS]-Obsessive and Compulsive subscales), lapses, relapses, and hepatic safety. Standardised psychosocial support was provided to both arms. RESULTS: Baseline characteristics were well matched between groups (mean MELD 12.6 vs. 12.7; CTP score 5.9 vs. 6.2; age 42.9 vs. 44.3 years). AUDIT and OCDS scores were comparable between groups. Abstinence at 12 weeks was significantly higher with naltrexone: 64% (32/50) versus 22% (11/50), p < 0.001; OR 10.86 (95% CI: 1.89-62.2). Naltrexone significantly reduced lapses at 3 months (28% vs. 54%, p = 0.008) and showed a trend toward fewer heavy-drinking relapses (12% vs. 28%, p = 0.07). Maintenance of abstinence at 6 months favoured naltrexone (22% vs. 8%, p = 0.09). No patient developed hepatic decompensation attributable to study medication, and no AST/ALT elevation exceeding 5× ULN was observed in either group. Mean craving scores were lower with naltrexone by week 12 than with placebo: OCDS-O score (6.63 ± 1.16 vs. 9.29 ± 1.78, p < 0.01) and OCDS-C score (6.35 ± 1.23 vs. 9.02 ± 1.86, p < 0.01). Adverse events were comparable between the groups. CONCLUSION: Naltrexone is safe and effective in patients with compensated alcohol-associated cirrhosis, achieving a threefold higher abstinence rate and significantly reducing craving compared with placebo. These findings support the use of naltrexone as a pharmacological option in patients with compensated AaC and AUD. TRIAL REGISTRATION: NCT04391764.

Humans↗

PubMed2026

Therapeutic-drug-monitoring-based ATG Targeted Dosing Strategy in Unmanipulated Haploidentical Haematopoietic Stem Cell Transplantation: a randomized, multicenter, phase 3 clinical trial.

Anti-thymocyte globulin (ATG) has been a standard prophylaxis for graft-versus-host disease (GVHD). However, the pharmacokinetics of ATG in vivo vary significantly, and weight-based fixed dosing may not optimize efficacy while minimizing toxicity. We investigated the clinical results of a therapeutic-drug-monitoring (TDM)-based, dose-optimized ATG strategy versus weight-based fixed dosing in haploidentical haematopoietic stem cell transplantation (NCT05166967). Patients were randomly assigned in a 1:1 ratio to receive a targeted dose of ATG or a fixed dose of 10 mg/kg. The primary endpoint was the 365-day graft-versus-host disease-free and relapse-free survival (GRFS). From January 1, 2022, to January 16, 2024, 204 patients were enrolled, with 102 patients in each group. The 365-day GRFS was higher in the targeted dose group (66.7%) than in the fixed dose group (50.0%; hazard ratio [HR], 0.666; 95% confidence interval [CI], 0.4456 to 0.9954; P = 0.048). The cumulative incidence of moderate to severe chronic GVHD at day 365 was significantly lower in the targeted dose group (9.8%; 95% CI, 5.0 to 16.5) compared with the fixed dose group (22.5%; 95% CI, 15.0 to 31.1; P = 0.026). Fewer grade 3-5 infections were reported in the targeted dose group (44.1%) than in the fixed dose group (70.6%; P < 0.001). More patients in the targeted dose group achieved optimal ATG exposure (P = 0.007) and superior CD4+ T-cell reconstitution (P = 0.002). These findings support the clinical utility of a TDM-based individualized ATG dosing strategy that balances efficacy and toxicity for GVHD prophylaxis in allogeneic stem cell transplantation. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05166967.

Humans↗

PubMed2026

The Efficacy of Pharmacotherapy Intervention on Anthropometric Outcomes in Survivors of Childhood Brain Tumors: An Updated Systematic Review and Meta-Analysis.

INTRODUCTION: Many survivors of childhood brain tumors face long-term adverse health outcomes like obesity. Uncertainties surround the effect of interventions to manage obesity-related outcomes in survivors of childhood brain tumors. The goal of this updated systematic review and meta-analysis was to provide the best estimate of the treatment efficacy of pharmacotherapy intervention on anthropometric outcomes in this pediatric population. METHODS: We searched CENTRAL, MEDLINE, EMBASE, CINAHL, PsycINFO, PubMed, ClinicalTrials.gov, and ProQuest for articles published from January 1, 2015, to January 31, 2025. A meta-analysis was performed using the generic inverse-variance method in RevMan 5.4. Heterogeneity was assessed using the Cochrane Q test and the I2 statistic. We used the GRADE approach to determine the certainty of evidence. RESULTS: A total of six studies met the inclusion criteria: four newly identified studies published after January 1, 2015 (125 participants), and two from the previously published review (23 participants). The pooled estimate showed no significant change in body mass index z-score after intervention (mean difference = -0.02; 95% CI: -0.06 to 0.02, I2 = 0%; 4 studies, 94 participants; low certainty of evidence). Similar pooled effects were observed across other outcomes; however, individual studies reported significant changes in some outcomes within the treatment groups after the intervention. CONCLUSION: Pharmacological agents showed no significant change in anthropometric outcomes for survivors of childhood brain tumors. Further trials are needed to assess the efficacy of pharmacological agents and to identify subgroups most likely to benefit.

Humans↗