BACKGROUND:Whether anticoagulation alone is an adequate treatment for acute, intermediate-risk pulmonary embolism is uncertain. METHODS:We conducted a multinational, adaptive-design trial with blinded outcome adjudication. Patients with intermediate-risk pulmonary embolism (with a ratio of right ventricular end-diastolic diameter to left ventricular end-diastolic diameter of ≥1.0 and an elevated troponin level) were eligible if they had at least two indicators of cardiorespiratory distress (systolic blood pressure of ≤110 mm Hg, a heart rate of ≥100 beats per minute, or a respiratory rate of >20 breaths per minute). Patients were randomly assigned to undergo ultrasound-facilitated, catheter-directed fibrinolysis with alteplase plus anticoagulation (the intervention group) or anticoagulation alone (the control group) according to prespecified treatment protocols. The primary outcome was a composite of pulmonary embolism-related death, cardiorespiratory decompensation or collapse, or symptomatic recurrence of pulmonary embolism within 7 days. RESULTS:The intention-to-treat population comprised 544 patients: 273 in the intervention group and 271 in the control group. The mean (±SD) age was 58.2±13.5 years, and 42.6% of the patients were women. A primary-outcome event occurred in 11 patients (4.0%; 95% confidence interval [CI], 2.3 to 7.1) in the intervention group and 28 (10.3%; 95% CI, 7.2 to 14.5) in the control group (relative risk, 0.39; 95% CI, 0.20 to 0.77; P = 0.005). The effect was driven primarily by a lower risk of cardiorespiratory decompensation or collapse in the intervention group. Major bleeding occurred within 7 days after randomization in 11 patients (4.1%) in the intervention group and 6 (2.2%) in the control group (P = 0.32); major bleeding occurred within 30 days in 11 patients (4.1%) and 8 patients (3.0%), respectively (P = 0.64). No substantial between-group differences in the incidence of other serious adverse events were observed up to 30 days after randomization; no intracranial hemorrhage occurred. CONCLUSIONS:In patients with acute, intermediate-risk pulmonary embolism, ultrasound-facilitated, catheter-directed fibrinolysis plus anticoagulation led to a lower risk of the composite of pulmonary embolism-related death, cardiopulmonary decompensation or collapse, or symptomatic recurrence of pulmonary embolism within 7 days than anticoagulation alone. (Funded by Boston Scientific; HI-PEITHO ClinicalTrials.gov number, NCT04790370.).
Background Hospital sink drains are increasingly recognized as important environmental reservoirs of multidrug-resistant Gram-negative bacteria and contributors to healthcare-associated infections. Conventional chemical disinfection strategies have limited and transient efficacy and contribute to environmental pollution through the release of chemical biocides. Probiotic-based approaches relying on competitive exclusion represent a promising alternative for the sustainable control of hospital microbial reservoirs. Material and methods In this study, we evaluated the inhibitory activity of two probiotic strains, Bacillus amyloliquefaciens NBS31007 and Bacillus velezensis S499, against nineteen strains of Gram-negative pathogens isolated from hospital sink drains. They belonged to the species Klebsiella pneumoniae , Enterobacter cloacae complex, Citrobacter freundii , and Pseudomonas aeruginosa , and produced extended-spectrum β-lactamases (ESBL) or carbapenemases. Reference strains of each species were used as controls. Bacillus strains were pre-cultured under oligotrophic conditions mimicking sink drain environments and subsequently challenged with low inocula of pathogenic strains. Pathogen growth was quantified after 24 hours of co-culture, and compared with growth in the absence of Bacillus . Results Both Bacillus strains inhibited the growth of all tested drain-related and reference strains, with reductions ranging from 1.0 to 6.1 log₁₀ CFU reduction ( P -values < 6.51 10 − 4 ) depending on the bacterial species and isolate. Overall, B. amyloliquefaciens NBS31007 and B. velezensis S499 displayed comparable inhibitory capacities, with only limited strain-dependent differences. Conclusions These findings provide proof of concept that probiotic Bacillus pre-cultures can limit the establishment of ESBL- and carbapenemase-producing Gram-negative pathogens in hospital sink drains. This biocontrol strategy may represent a complementary infection prevention approach aligned with antimicrobial resistance mitigation and One Health principles.
Abstract Backgrounds Following the latest studies, the choice between chest tube drainage and simple aspiration remains debated in the treatment of spontaneous pneumothorax. The aim of this study was to compare the efficacy between SA and CTD in treatment of spontaneous pneumothorax in adults in a systematic review and meta-analysis. Methods Literature research was conducted with Medline, Embase and Central databases from inception to march 2025. The target population is adults presenting a SP managed by SA or CTD among randomized control trials and retrospective comparative studies. The RoB-2 and NOS was carried out for the quality assessment of studies. A meta-analysis was conducted with inverse variance and a random effect model. Results 19 studies were included in the meta-analysis. The results of meta-analysis comparing SA vs. CTD were as follows: immediate success OR = 0.42 (95% CI= [0.16, 1.09], p = 0.07), adverse effect occurrence OR = 0.22 (95% CI=[0.08, 0.61], p = 0.004), length of hospitalization MD = -2.59 (95% CI=[-3.57, -1.61], p < 0.001), pain score MD=-1.34 (95% CI=[-1.74, -0.95], p < 0.001). Conclusion This meta-analysis shows no difference in the efficacy between SA and CTD in the treatment of SP, especially for PSP. However, the additional benefits of SA over CTD in clinical patient management support prioritizing this strategy, in line with international guideline recommendations.
Background and ObjectivesDevelopmental and epileptic encephalopathies (DEEs) with early burst-suppression EEG (EIDEE-BS) are among the most severe neonatal epileptic syndromes, typically presenting in the first months of life with refractory seizures and profound neurodevelopmental impairment. Although variants in the KCNQ2, STXBP1, and SCN2A genes are recognized as major causes, the full genetic spectrum remains uncertain. We aimed to delineate the electroclinical characteristics, genetic etiologies, and long-term outcomes in a large MRI-negative EIDEE-BS cohort.MethodsWe retrospectively analyzed 110 patients with BS EEG enrolled from a database of 1,540 individuals with suspected genetic epilepsies (2008-2023). Clinical, EEG, and genetic data were systematically collected. Patients were stratified into 4 groups: KCNQ2, STXBP1, "other pathogenic variants," and "without a genetic diagnosis." EEG traces were reviewed independently, and outcomes were assessed through long-term follow-up.ResultsPathogenic or likely pathogenic variants were identified in 62.7% of patients and involved 23 genes, including 2 copy number variants. KCNQ2 (n = 24) and STXBP1 (n = 16) accounted for one-third of diagnoses, whereas SCN2A (n = 3) and KCNT1 (n = 2) were less frequent. In KCNQ2 cases, seizures and BS onset occurred earlier than in STXBP1 cases: mean 2 days vs 6 weeks for seizures and 3 days vs 2 months for BS, respectively. A typical BS pattern (bursts longer than suppressions) strongly correlated with KCNQ2 and STXBP1 variants. Novel associations were found with DPM1, GRIN2A, KCNT2, PIGO, PURA, WWOX, and candidate genes (KMT2E, SNAP25, and SYT1). Most variants were de novo heterozygous; however, recessive and X-linked inheritance patterns were also observed. Mortality was high (25%), primarily from status epilepticus and complications of severe disability. Most patients (72.5%) had persistent seizures at follow-up (a mean of 6.5 years), as well as profound intellectual disabilities, irrespective of genotype.DiscussionThis large series highlights the strong monogenic basis of EIDEE-BS. KCNQ2, STXBP1, and SCN2A were the most commonly affected genes. Early EEG features, particularly BS timing and morphology, can help anticipate the underlying genotype and guide precision therapy, including the early use of sodium channel blockers in selected cases. These findings support recent ILAE reclassification efforts and underscore the importance of comprehensive genomic testing for improved diagnosis and counseling.
