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Intravenous thrombolysis (IVT) remains a cornerstone in the management of acute ischemic stroke (AIS). Since the landmark NINDS and ECASS III trials, numerous randomized controlled trials (RCTs) have expanded IVT indications beyond the initial 4.5-h window. Advanced imaging modalities, including perfusion-based and diffusion/fluid-attenuated inversion recovery (FLAIR) mismatch, have enabled individualized patient selection, leading to positive outcomes in trials such as WAKE-UP, EXTEND, and EXPECTS. Despite these advances, key challenges remain. Patients with large ischemic cores, those on direct oral anticoagulants (DOACs), and those with minor non-disabling strokes lack robust evidence supporting IVT use. Moreover, while alternative thrombolytics like tenecteplase have shown promise, additional data are needed to redefine the standard of care. Adjunctive pharmacologic therapies (e.g., glycoprotein IIb/IIIa or thrombin inhibitors) have yet to demonstrate consistent benefit. This review highlights the progress, limitations, and future directions of IVT, emphasizing a shift from rigid temporal thresholds toward physiology-based, patient-centered stroke reperfusion strategies.

Background: Inflammatory bowel disease (IBD) carries a hereditary risk, which is higher through maternal, rather than paternal, inheritance. Like their mothers, children born to mothers with IBD have an altered microbiome shortly after birth.

Methods: To investigate whether this altered microbiome persists later in life and affects the intestinal mucosa, the fecal microbiome was analyzed in samples from 44 infants ranging from 0 to 10 years of age born to 26 women with IBD. Forty-four age-matched children of 29 women without IBD served as controls. Fecal microbiota transplantation (FMT) to germ-free mice was carried out from 4-year-olds born to mothers with IBD and controls. Markers of inflammation, barrier function, and metabolic changes were investigated.

Findings: Intestinal microbiomes were more similar between women with IBD and their children than between control mothers and their offspring. Microbial changes were noticeable in children from mothers with IBD from the age of 4 years compared to children of controls. No inflammatory response was present in the mucosa of mice receiving FMT from children of mothers with IBD; however, mesenteric lymph node enlargement and decreased expression of barrier genes Zo1 and Ocln were seen in mice receiving FMT from these children compared to controls. Additionally, reduced colonic expression of the immunological tolerance enzyme Ido1 coincided with decreased serum kynurenine/tryptophan ratios.

Conclusions: Fecal microbiomes of children of mothers with IBD exhibit characteristics that reduce epithelial tight junction barrier genes and tolerogenic tryptophan metabolism. Microbiome-induced gut barrier disruptions may contribute to an enhanced IBD predisposition in infants of mothers with IBD.

Funding: This work was funded by ZonMw.

The analysis of cell-free DNA (cfDNA) has emerged as a cornerstone of minimally invasive liquid biopsies. We summarize the key advancements of the last five years-deepening insights into fundamental cfDNA biology, innovations in wet- and dry-lab approaches, and the amassment of clinical outcome data-and discuss prospects of this field for the coming half-decade.

Fecal microbiota transplant plus dietary change to restore the imbalance of an individual's microbiome to relieve disorders such as inflammatory bowel disease has not been established but has promise. In this commentary, we suggest the need to embrace a more nuanced, personalized approach, one that considers microbial functionality, dietary context, and host compatibility.

The phase 3 STELLAR-303 trial¹ demonstrated a significant overall survival benefit of zanzalintinib plus atezolizumab over regorafenib in refractory microsatellite-stable (MSS) metastatic colorectal cancer, marking the first phase 3 success of an immunotherapy-based regimen in this population. These results may reshape treatment paradigms and renew interest in biomarker-guided immunotherapy for MSS disease.

Background: Dysregulation of bromodomain and extra-terminal domain (BET) proteins causes aberrant acetylation of histones, triggering oncogene expression in malignancies. TQB3617 is an orally administered BET inhibitor that competitively binds to bromodomains and inhibits their activities.

Methods: This phase 1 trial assessed the safety, pharmacokinetics, and efficacy of TQB3617 in patients with relapsed or refractory lymphomas. The primary endpoints were the safety, dose-limiting toxicity (DLT), and the recommended phase 2 dose (RP2D). Secondary endpoints included pharmacokinetics and efficacy. The trial is registered with ClinicalTrials.gov: NCT05110807.

Findings: Using a 3+3 dose-escalation design, 39 patients were enrolled and treated with TQB3617 (0.05-0.25 mg) once daily. DLTs were reported in one patient at 0.1 mg with grade 3 herpes zoster and one patient at 0.25 mg with grade 3 thrombocytopenia and subcutaneous hemorrhage. The safety monitoring committee selected 0.1 mg once daily in two 21-day cycles followed by 14 days on and 7 days off in subsequent cycles as the RP2D. The most common grade 3-4 treatment-related adverse event (TRAE) was thrombocytopenia (14/39, 36%). Three patients discontinued study treatment due to TRAEs (all thrombocytopenia). The overall response rate (ORR) was 31% (12/39; complete response in 4 patients), with ORRs of 31% (5/16) in patients with Hodgkin's lymphoma, 31% (5/16) in patients with T cell lymphoma, and 29% (2/7) in patients with B cell lymphoma.

Conclusions: TQB3617 showed an acceptable safety profile and promising efficacy in patients with relapsed or refractory lymphomas.

Funding: This work was sponsored by Chia Tai Tianqing Pharmaceutical Group Co., Ltd. and funded by the National Natural Science Foundation of China.

Background: Childhood obesity is a pressing global public health challenge requiring scalable prevention strategies. This study evaluated a tiered school-family-clinic intervention for obesity prevention among primary schoolchildren in China.

Methods: This cluster randomized controlled trial enrolled 1,627 third-grade students (intervention: n = 838; control: n = 789) from six primary schools in Ningbo, China. Intervention intensity was tailored to baseline weight status. In intervention schools, children without overweight or obesity received OptiChild, comprising health education and school weight-management policies. Children with overweight or obesity received SCIENT, adding teacher-led structured physical activity and individualized family dietary guidance from clinical nutritionists, supported by mobile health tools. Control schools maintained standard curricula. The primary outcome was change in body mass index (BMI). Secondary outcomes included BMI Z score, body fat distribution, blood pressure, and health behaviors.

Findings: After one academic year, BMI gain was attenuated in the intervention vs. control group (+0.02 vs. +0.24 kg/m²; mean difference [MD] -0.25; p = 0.006). Overweight/obesity prevalence declined from 24.8% to 18.9% in intervention schools vs. 23.6%-21.0% in controls (p = 0.015). OptiChild slowed BMI increase (+0.08 vs. +0.25 kg/m²; MD -0.19; p = 0.048) in children without baseline overweight and reduced incident overweight/obesity by 68% (1.1% vs. 3.5%; p = 0.007). SCIENT reduced BMI (-0.19 vs. +0.21 kg/m²; MD -0.38; p < 0.001). Both interventions improved health behaviors, with no adverse events reported.

Conclusions: A tiered school-family-clinic intervention effectively mitigated BMI gain and reduced obesity prevalence, with promising implications for broader public health adoption.

Funding: Major Science and Technology Projects for Health of Zhejiang Province.

TL1A inhibitors offer a novel therapeutic strategy in inflammatory bowel disease by combining anti-inflammatory effects with potential antifibrotic activity. Phase 2 studies show clinical efficacy and a favorable safety profile. Ongoing phase 3 trials will further define their role, including the utility of genetic predictors to guide patient-specific therapy.

The manuscript by Fujii et al. describes the first in-human trial testing of the safety and feasibility of intrarectal perfluorodecalin, a potential method of enteral ventilation. The investigators found that a one-time dose of perfluorodecalin was safe and tolerated without significant adverse effects in healthy men. More work is needed to demonstrate whether this compound can effectively improve oxygenation in critically ill patients.