BACKGROUND:Data are needed on the effect of oxygen delivered through a high-flow nasal cannula, as compared with standard oxygen therapy, on intubation and mortality in patients with acute hypoxemic respiratory failure. METHODS:In this multicenter, open-label trial, we randomly assigned patients who had acute hypoxemic respiratory failure to receive high-flow-oxygen or standard-oxygen therapy. All the patients had a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen of 200 or less, a respiratory rate of more than 25 breaths per minute, and pulmonary infiltrate on chest imaging. The primary outcome was death by day 28. RESULTS:A total of 1116 patients underwent randomization. Of these patients, 1110 (556 in the high-flow-oxygen group and 554 in the standard-oxygen group) were included in the analysis. Mortality at day 28 was 14.6% (in 81 of 556 patients) in the high-flow-oxygen group and 14.6% (in 81 of 554 patients) in the standard-oxygen group (difference, -0.05 percentage points; 95% confidence interval [CI], -4.21 to 4.10; P = 0.98). The incidence of intubation by day 28 was 42.4% (in 236 of 556 patients) in the high-flow-oxygen group and 48.4% (in 268 of 554 patients) in the standard-oxygen group (difference, -5.93 percentage points; 95% CI, -11.78 to -0.08). Serious adverse events (cardiac arrest or pneumothorax) occurred during spontaneous breathing in 13 patients (2.3%) in the high-flow-oxygen group and in 6 patients (1.1%) in the standard-oxygen group. CONCLUSIONS:Among patients with acute hypoxemic respiratory failure, the use of oxygen delivered through a high-flow nasal cannula did not significantly reduce mortality at day 28. (Funded by the French Ministry of Health and Fisher and Paykel Healthcare; SOHO ClinicalTrials.gov number, NCT04468126.).
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.
Aim. To examine the functional state of the autonomic nervous system (ANS) in postpartum women with multiple organ/system dysfunction/failure syndrome, depending on the dominant organ damage using non-invasive monitoring of cardiointerval variation. Material and methods . The study included 100 postpartum women with multiple organ/system dysfunction/failure syndrome (MOSDFS). They were divided into four groups: Group 1 (40 patients) with predominant acute kidney injury; Group 2 (30 patients) with primary manifestations of acute liver failure; Group 3 (30 patients) with dominant acute respiratory distress syndrome; and the control group (30 healthy women of reproductive age). All patients had MOSDFS, with one dysfunction being predominant and the others at various stages and degrees of severity (80% with three affected organs and 20% with two organs). Dysfunction of the central nervous system (CNS) and its autonomic divisions were observed in all cases. An assessment of spectral and fractal analyses was conducted along with an evaluationof the degree of integration of systemic connections forming extracardiac regulation of heart rhythm by the CNS. Additionally, heart rate variability and the state of autonomic balance were also analyzed. Results and discussion . Non-invasive RR-interval monitoring in the studied postpartum women revealed significant dysfunction of the CNS and ANS in a form of imbalances and various zones of functional states across all groups, regardless of the predominant organ damage and subsequent functional failure. These disruptions manifested. Conclusion. Among five conditional zones of autonomic states (stable autonomic balance, adaptation, subcritical, critical, and supercritical), 45% of postpartum women were in the critical zone and 55% in the supercritical zone. This necessitates a personalized approach to diagnosis and treatment.
Antibiotic resistance is an escalating public health challenge, particularly among Enterobacteriaceae and Pseudomonas aeruginosa. In this study conducted at a burn center in Tunisia, we collected 307 non-redundant strains of Enterobacteriaceae from predominantly hospitalized patients, with a majority in the burn intensive care unit (59%), the primary identified species being Klebsiella pneumoniae (34.8%). We evaluated the efficacy of two antibiotics, ceftazidime-avibactam (CZA) and ceftolozane-tazobactam (CT). The results revealed that the overall resistance to CZA was 11.7%, while to CT it was 25.7%. CZA proved to be the second most sensitive molecule among all tested antibiotics, following fosfomycin. Among strains resistant to third-generation cephalosporins, 73.3% were sensitive to CZA, and 41.5% to CT. Out of seventy-nine CT-resistant strains, eight were ESBL producers, twenty-two were high-level cephalosporinases, thirty-three carried blaNDM, twelve carried blaOXA48, and four carried both blaNDM and blaOXA-48. Indeed, blaNDM were the most prevalent carbapenemases. For Pseudomonas aeruginosa strains (n=161), resistance to CZA was 42.2%, and to CT it was 47.8%. These antibiotics ranked as the second and third most active beta-lactams after aztreonam. Among the 71 strains of CZA and carbapenem-resistant P. aeruginosa, 54.1% produced VIM2. Resistance to enterobacteriaceae against CZA and CT is relatively high in our study. However, CZA remains a salvage therapy for infections caused by carbapenem-resistant organisms, and its use should be considered only after documentation and in the absence of other alternatives among β-lactams. For P. aeruginosa, CZA currently represents the most active β-lactam against CAZ-R strains and the second most active molecule overall, including those producing carbapenemases.
Le groupe FEMMIR s’est formé en 2019 pour se pencher sur les problématiques de genre en réanimation : égalité femmes-hommes, discrimination et violences ressenties par les femmes médecin. La première étape de son travail a été d’établir un état des lieux : le nombre de femmes et d’hommes est relativement semblable parmi les praticien-nes de médecine intensive et réanimation, mais la proportion de femmes diminue aux postes-clés (chef-fes de service, professeur-es, intervenant-es en congrès, expert-es intervenant dans les médias) ; de nombreuses femmes ont déjà vécu par ailleurs des discriminations ou des comportements sexistes voire du harcèlement ou des agressions sexuelles. La deuxième étape a été d’entreprendre des actions pour promouvoir l’égalité des genres et la sensibilisation aux discriminations : engagement pour la parité au sein des commissions, des congrès et des journaux, création d’une liste d’expertes, publication d’articles de recherche à propos du genre chez les patient-es ou les praticien-nes, mis en place d’un enseignement auprès des internes et de formations aux professionnel-les de santé, communication sur les réseaux sociaux et création de réseaux inter-spécialités et internationaux. Le groupe va poursuivre et consolider son action sur ces sujets dans les années à venir.
