Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Relative Contribution of Gestational Weight Gain, Gestational Diabetes, and Maternal Obesity to Neonatal Fat Mass

International audienceMaternal nutritional and metabolic status influence fetal growth. This study investigated the contribution of gestational weight gain (GWG), gestational diabetes (GDM), and maternal obesity to birthweight and newborn body fat. It is a secondary analysis of a prospective study including 204 women with a pregestational body mass index (BMI) of 18.5-24.9 kg/m 2 and 219 women with BMI ≥ 30 kg/m 2. GDM was screened in the second and third trimester and was treated by dietary intervention, and insulin if required. Maternal obesity had the greatest effect on skinfolds (+1.4 mm) and cord leptin (+3.5 ng/mL), but no effect on birthweight. GWG was associated with increased birthweight and skinfolds thickness, independently from GDM and maternal obesity. There was an interaction between third trimester weight gain and GDM on birthweight and cord leptin, but not with maternal obesity. On average, +1 kg in third trimester was associated with +13 g in birthweight and with +0.64 ng/mL in cord leptin, and a further 32 g and 0.89 ng/mL increase in diabetic mothers, respectively. Maternal obesity is the main contributor to neonatal body fat. There is an independent association between third trimester weight gain, birthweight, and neonatal body fat, enhanced by GDM despite intensive treatment

Low dose of morphine to relieve dyspnea in acute respiratory failure (OpiDys): protocol for a double-blind randomized controlled study

International audienceBackground Dyspnea is common and severe in intensive care unit (ICU) patients managed for acute respiratory failure. Dyspnea appears to be associated with impaired prognosis and neuropsychological sequels. Pain and dyspnea share many similarities and previous studies have shown the benefit of morphine on dyspnea in patients with end-stage onco-hematological disease and severe heart or respiratory disease. In these populations, morphine administration was safe. Here, we hypothesize that low-dose opioids may help to reduce dyspnea in patients admitted to the ICU for acute respiratory failure. The primary objective of the trial is to determine whether the administration of low-dose titrated opioids, compared to placebo, in patients admitted to the ICU for acute respiratory failure with severe dyspnea decreases the mean 24-h intensity of dyspnea score. Methods In this single-center double-blind randomized controlled trial with 2 parallel arms, we plan to include 22 patients (aged 18–75 years) on spontaneous ventilation with either non-invasive ventilation, high flow oxygen therapy or standard oxygen therapy admitted to the ICU for acute respiratory failure with severe dyspnea. They will be assigned after randomization with a 1:1 allocation ratio to receive in experimental arm administration of low-dose titrated morphine hydrochloride for 24 h consisting in an intravenous titration relayed subcutaneously according to a predefined protocol, or a placebo (0.9% NaCl) administered according to the same protocol in the control arm. The primary endpoint is the mean 24-h dyspnea score assessed by a visual analog scale of dyspnea. Discussion To our knowledge, this study is the first to evaluate the benefit of opioids on dyspnea in ICU patients admitted for acute respiratory failure. Trial registration ClinicalTrials.gov NCT04358133 . Registered on 24 April 2020

Characteristics, management, and prognosis of elderly patients with COVID-19 admitted in the ICU during the first wave: insights from the COVID-ICU study

International audienceAbstract Background The COVID-19 pandemic is a heavy burden in terms of health care resources. Future decision-making policies require consistent data on the management and prognosis of the older patients (> 70 years old) with COVID-19 admitted in the intensive care unit (ICU). Methods Characteristics, management, and prognosis of critically ill old patients (> 70 years) were extracted from the international prospective COVID-ICU database. A propensity score weighted-comparison evaluated the impact of intubation upon admission on Day-90 mortality. Results The analysis included 1199 (28% of the COVID-ICU cohort) patients (median [interquartile] age 74 [72–78] years). Fifty-three percent, 31%, and 16% were 70–74, 75–79, and over 80 years old, respectively. The most frequent comorbidities were chronic hypertension (62%), diabetes (30%), and chronic respiratory disease (25%). Median Clinical Frailty Scale was 3 (2–3). Upon admission, the PaO 2 /FiO 2 ratio was 154 (105–222). 740 (62%) patients were intubated on Day-1 and eventually 938 (78%) during their ICU stay. Overall Day-90 mortality was 46% and reached 67% among the 193 patients over 80 years old. Mortality was higher in older patients, diabetics, and those with a lower PaO 2 /FiO 2 ratio upon admission, cardiovascular dysfunction, and a shorter time between first symptoms and ICU admission. In propensity analysis, early intubation at ICU admission was associated with a significantly higher Day-90 mortality (42% vs 28%; hazard ratio 1.68; 95% CI 1.24–2.27; p < 0·001). Conclusion Patients over 70 years old represented more than a quarter of the COVID-19 population admitted in the participating ICUs during the first wave. Day-90 mortality was 46%, with dismal outcomes reported for patients older than 80 years or those intubated upon ICU admission

VNtyper enables accurate alignment-free genotyping of MUC1 coding VNTR using short-read sequencing data in autosomal dominant tubulointerstitial kidney disease

Summary: The human genome comprises approximately 3% of tandem repeats with variable length (VNTR), a few of which have been linked to human rare diseases. Autosomal dominant tubulointerstitial kidney disease—MUC1 (ADTKD-MUC1) is caused by specific frameshift variants in the coding VNTR of the MUC1 gene. Calling variants from VNTR using short-read sequencing (SRS) is challenging due to poor read mappability. We developed a computational pipeline, VNtyper, for reliable detection of MUC1 VNTR pathogenic variants and demonstrated its clinical utility in two distinct cohorts: (1) a historical cohort including 108 families with ADTKD and (2) a replication naive cohort comprising 2,910 patients previously tested on a panel of genes involved in monogenic renal diseases. In the historical cohort all cases known to carry pathogenic MUC1 variants were re-identified, and a new 25bp-frameshift insertion in an additional mislaid family was detected. In the replication cohort, we discovered and validated 30 new patients

Lower Rate of Daily Smokers With Symptomatic COVID-19: A Monocentric Self-Report of Smoking Habit Study

International audienceBackground: Identification of prognostic factors in COVID-19 remains a global challenge. The role of smoking is still controversial.Methods: PCR-positive in- and outpatients with symptomatic COVID-19 from a large French University hospital were systematically interviewed for their smoking status, use of e-cigarette, and nicotinic substitutes. The rates of daily smokers in in- and outpatients were compared using the same smoking habit questionnaire to those in the 2019 French general population, after standardisation for sex and age.Results: The inpatient group was composed of 340 patients, median age of 66 years: 203 men (59.7%) and 137 women (40.3%), median age of both 66 years, with a rate of 4.1% daily smokers (CI 95% [2.3–6.9]) (5.4% of men and 2.2% of women). The outpatient group was composed of 139 patients, median age of 44 years: 62 men (44.6%, median age of 43 years) and 77 women (55.4%, median age of 44 years). The daily smoker rate was 6.1% (CI 95% [2.7–11.6], 5.1% of men and 6.8% of women). Amongst inpatients, daily smokers represented 2.2 and 3.4% of the 45 dead patients and of the 29 patients transferred to ICU, respectively. The rate of daily smokers was significantly lower in patients with symptomatic COVID-19, as compared to that in the French general population after standardisation by age and sex, with standardised incidence ratios (SIRs) of 0.24 [0.12–0.48] for outpatients and 0.24 [0.14–0.40] for inpatients.Conclusions: Daily smoker rate in patients with symptomatic COVID-19 is lower as compared to the French general populatio

Retrieval of severe acute respiratory failure patients on extracorporeal membrane oxygenation: Any impact on their outcomes?

International audienceObjective: Mobile extracorporeal membrane oxygenation (ECMO) retrieval teams (MERTs) assure ECMO implantation and under-ECMO retrieval of patients with most severe acute respiratory failure (ARF) to experienced ECMO centers. Although described as feasible, mobile ECMO has only been poorly evaluated in comparison with on-site implantation. This study was undertaken to compare the indications, characteristics, and outcomes of MERT-implanted patients with venovenous (VV)-ECMO versus those implanted on site in our intensive care unit (ICU).Methods: Retrospective, single-center study.Results: Among 157 VV-ECMO implantations from 2008 to 2012, the MERT hooked up 118 (75%) patients with refractory ARF, as reflected by their median partial pressure of O2 in arterial blood/fraction of inspired oxygen of 58 (interquartile range, 50-73). ARF was accompanied by severe multiorgan failure, with a median Simplified Acute Physiology Score-II of 71 (61-81), median Sequential Organ Failure Assessment score of 14 (10-16), and with 82% of the patients receiving inotropes. All patients were transported by ground ambulance: median distance was 15 (6-25) km, and median transport time was 35 (25-35) minutes, during which no major ECMO system-related event occurred. For the MERT- and on-site-implanted groups, ICU mortality was comparable (46.6% vs 53.8%, respectively, P = .5), as were ECMO-related complication rates (53.4% of MERT vs 53.8% of on-site-implanted groups, P = 1.0). According to multivariable analysis, MERT ECMO implantation was not associated with ICU mortality (odds ratio, 1.1; 95% confidence interval, 0.4-2.7; P = .85).Conclusions: ICU mortality and ECMO-related complications of patients with MERT-implanted VV-ECMO who were transferred to our ECMO referral center were comparable with those implanted on site by the same team, thereby supporting this strategy to manage patients with severe ARF

Effect of topiramate on eating behaviours in Prader-Willi syndrome: TOPRADER double-blind randomised placebo-controlled study

International audiencePrader-Willi Syndrome (PWS) is a rare genetic syndrome leading to severe behavioural disorders and mild cognitive impairment. The objective of this double-blind randomised placebo-controlled trial was to study the efficacy and tolerance of topiramate on behavioural disorders in patients with PWS. Participants (aged 12-45 years) had genetically confirmed PWS and severe irritability/impulsivity, eating disorders and/or obesity, and skin picking. Thirty-two participants received a placebo (PBO), and 30 participants received topiramate (TOP) (50-200 mg/day) for 8 weeks. The primary outcome was the rate of responders using the Clinical Global Impression-Improvement (CGI-I) scale. The secondary outcome measures included the Aberrant Behaviour Checklist, the Dykens Hyperphagia Questionnaire (DHK), the Self-Injurious Behaviour Scale (SIBS) and the body mass index (BMI). We found no significant difference in the primary outcome (the CGI-I): 9 (30%) patients were very much or much improved in the TOP group compared to 7 (22.6%) patients in the PBO group. However, the DHK behaviour and severity scores improved significantly more over time in patients treated with topiramate versus those receiving a placebo, with a significant dose-effect relationship. DHK scores were also significantly associated with genetic subtypes and hospitalisation status. The effects of topiramate on eating behaviours remained significant after adjusting for genetic subtype and hospitalisation. Topiramate had therefore a significant effect on eating disorders, with a dose-effect relationship. Given the burden of eating disorders in PWS, we believe that topiramate may become the first psychotropic option within the global care of obesity in individuals with PWS

Early prone positioning in acute respiratory distress syndrome related to COVID-19: a propensity score analysis from the multicentric cohort COVID-ICU network-the ProneCOVID study.

peer reviewed[en] BACKGROUND: Delaying time to prone positioning (PP) may be associated with higher mortality in acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19). We evaluated the use and the impact of early PP on clinical outcomes in intubated patients hospitalized in intensive care units (ICUs) for COVID-19. METHODS: All intubated patients with ARDS due to COVID-19 were involved in a secondary analysis from a prospective multicenter cohort study of COVID-ICU network including 149 ICUs across France, Belgium and Switzerland. Patients were followed-up until Day-90. The primary outcome was survival at Day-60. Analysis used a Cox proportional hazard model including a propensity score. RESULTS: Among 2137 intubated patients, 1504 (70.4%) were placed in PP during their ICU stay and 491 (23%) during the first 24 h following ICU admission. One hundred and eighty-one patients (36.9%) of the early PP group had a PaO2/FiO2 ratio > 150 mmHg when prone positioning was initiated. Among non-early PP group patients, 1013 (47.4%) patients had finally been placed in PP within a median delay of 3 days after ICU admission. Day-60 mortality in non-early PP group was 34.2% versus 39.3% in the early PP group (p = 0.038). Day-28 and Day-90 mortality as well as the need for adjunctive therapies was more important in patients with early PP. After propensity score adjustment, no significant difference in survival at Day-60 was found between the two study groups (HR 1.34 [0.96-1.68], p = 0.09 and HR 1.19 [0.998-1.412], p = 0.053 in complete case analysis or in multiple imputation analysis, respectively). CONCLUSIONS: In a large multicentric international cohort of intubated ICU patients with ARDS due to COVID-19, PP has been used frequently as a main treatment. In this study, our data failed to show a survival benefit associated with early PP started within 24 h after ICU admission compared to PP after day-1 for all COVID-19 patients requiring invasive mechanical ventilation regardless of their severity