Background The COVID-19 pandemic has led highly developed healthcare systems to the brink of collapse due to the large numbers of patients being admitted into hospitals. One of the potential prognostic indicators in patients with COVID-19 is frailty. The degree of frailty could be used to assist both the triage into intensive care, and decisions regarding treatment limitations. Our study sought to determine the interaction of frailty and age in elderly COVID-19 ICU patients. Methods A prospective multicentre study of COVID-19 patients ≥ 70 years admitted to intensive care in 138 ICUs from 28 countries was conducted. The primary endpoint was 30-day mortality. Frailty was assessed using the clinical frailty scale. Additionally, comorbidities, management strategies and treatment limitations were recorded. Results The study included 1346 patients (28% female) with a median age of 75 years (IQR 72–78, range 70–96), 16.3% were older than 80 years, and 21% of the patients were frail. The overall survival at 30 days was 59% (95% CI 56–62), with 66% (63–69) in fit, 53% (47–61) in vulnerable and 41% (35–47) in frail patients (p < 0.001). In frail patients, there was no difference in 30-day survival between different age categories. Frailty was linked to an increased use of treatment limitations and less use of mechanical ventilation. In a model controlling for age, disease severity, sex, treatment limitations and comorbidities, frailty was independently associated with lower survival. Conclusion Frailty provides relevant prognostic information in elderly COVID-19 patients in addition to age and comorbidities. Trial registration Clinicaltrials.gov: NCT04321265, registered 19 March 2020.

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BackgroundMechanical thrombectomy (MT) for acute ischemic stroke can be performed under local anesthesia, with or without conscious sedation (CS), or under general anesthesia (GA). The hemodynamic consequence of anesthetic drugs may explain why GA may be associated with worse outcomes. We evaluated the association between hypotension duration during MT and the 90 day functional outcome under both anesthetic regimens.MethodsPatients were included in this retrospective study if they had an ischemic stroke treated by MT under GA or CS. The main exposure variable was the time below 90% of the reference value of arterial pressure measured before MT. The primary outcome was poor functional outcome defined as a 90 day modified Rankin Score ≥3.Results371 patients were included in the study. GA was performed in 42%. A linear association between the duration of arterial hypotension and outcome was observed. The odds ratio for poor functional outcome of 10 min under 90% of the baseline mean arterial pressure was 1.13 (95% CI 1.06 to 1.21) without adjustment and 1.11 (95% CI 1.02 to 1.21) after adjustment for confounding factors. The functional outcome was poorer for patients treated under GA compared with CS, but the association with the depth of hypotension remained similar under both conditions.ConclusionIn this study, we observed a linear association between the duration of hypotension during MT and the functional outcome at 90 days. An aggressive and personalized strategy for the treatment of hypotension should be considered. Further trials should be conducted to address this question.

Purpose The number of patients ≥ 80 years admitted into critical care is increasing. Coronavirus disease 2019 (COVID-19) added another challenge for clinical decisions for both admission and limitation of life-sustaining treatments (LLST). We aimed to compare the characteristics and mortality of very old critically ill patients with or without COVID-19 with a focus on LLST. Methods Patients 80 years or older with acute respiratory failure were recruited from the VIP2 and COVIP studies. Baseline patient characteristics, interventions in intensive care unit (ICU) and outcomes (30-day survival) were recorded. COVID patients were matched to non-COVID patients based on the following factors: age (± 2 years), Sequential Organ Failure Assessment (SOFA) score (± 2 points), clinical frailty scale (± 1 point), gender and region on a 1:2 ratio. Specific ICU procedures and LLST were compared between the cohorts by means of cumulative incidence curves taking into account the competing risk of discharge and death. Results 693 COVID patients were compared to 1393 non-COVID patients. COVID patients were younger, less frail, less severely ill with lower SOFA score, but were treated more often with invasive mechanical ventilation (MV) and had a lower 30-day survival. 404 COVID patients could be matched to 666 non-COVID patients. For COVID patients, withholding and withdrawing of LST were more frequent than for non-COVID and the 30-day survival was almost half compared to non-COVID patients. Conclusion Very old COVID patients have a different trajectory than non-COVID patients. Whether this finding is due to a decision policy with more active treatment limitation or to an inherent higher risk of death due to COVID-19 is unclear. Supplementary Information The online version contains supplementary material available at 10.1007/s00134-022-06642-z.

Myoclonic epilepsy with ragged red fibers (MERRF) syndrome is a rare mitochondrial disease potentially associated with increased sensitivity to anesthesia and metabolic decompensation. We present the perioperative management in a 59-year-old man with MERRF scheduled for lipomatosis cure under general anesthesia (GA). Following a reduced fasting period, the patient had an uneventful balanced GA with propofol, sevoflurane, and rocuronium. The patient did not present metabolic decompensation nor malignant hyperthermia but prolonged neuromuscular blockade. Propofol and sevoflurane may be used in asymptomatic MERRF adult patients. Such patients present high risk of residual neuromuscular blockade that should be monitored and reversed.

Background We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15–20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases. Methods We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded. Results No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5–528.7, P = 1.1 × 10−4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3–8.2], P = 2.1 × 10−4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1–2635.4], P = 3.4 × 10−3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3–8.4], P = 7.7 × 10−8). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P = 1.68 × 10−5). Conclusions Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old.

Idiopathic pulmonary arterial hypertension (PAH) can cause right ventricular (RV) failure and death. It may progress to suprasystemic idiopathic PAH in some patients despite medical treatment, and there are limited therapeutic options. Atrial septostomy is an alternative treatment to reduce the RV afterload and improve left ventricular (LV) preload achieved at the expense of whole body desaturation. Lung transplantation is challenging because of an insufficient donor pool with a wait list mortality of 27%, 1 and long-term success limited by debilitation due to chronic disease, complications causing impaired mucus clearance, infections, and chronic lung allograft dysfunction. Based on previous observations of improved survival in Eisenmenger syndrome patients as compared to those with isolated IPAH, a new indication for surgical reverse Potts shunt creation was conceived. A Potts shunt is a window created between the left pulmonary artery and the descending aorta as a long-term alternative to lung transplantation that equalizes the pulmonary and systematic arterial pressures. 2 However,

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