Severe leptospirosis in tropical and non-tropical areas: A comparison of two french, multicentre, retrospective cohorts.

BACKGROUND: Leptospirosis is an anthropozoonosis that occurs worldwide but is more common in tropical regions. Severe forms may require intensive care unit (ICU) admission. Whether the clinical patterns and outcomes differ between tropical and non-tropical regions with similar healthcare systems is unclear. Our objective here was to address this issue by comparing two cohorts of ICU patients with leptospirosis managed in mainland France and in the overseas French department of Réunion, respectively. METHODOLOGY/PRINCIPAL FINDINGS: We compared two retrospective cohorts of patients admitted to intensive care for severe leptospirosis, one from Reunion Island in the Indian Ocean (tropical climate) and the other from metropolitan France (temperate climate). Chi-square and Student's t tests were used for comparisons. After grouping the two cohorts, we also performed multiple correspondence analysis and hierarchical clustering to search for distinct clinical phenotypes. The Réunion and Metropolitan France cohorts comprised 128 and 160 patients respectively. Compared with the Réunion cohort, the metropolitan cohort had a higher mean age (42.5±14.1 vs. 51.4±16.5 years, p<0.001). Severity scores, length of stay and mortality did not differ between the two cohorts. Three phenotypes were identified: hepato-renal leptospirosis (54.5%) characterized by significant hepatic, renal and coagulation failure, with a mortality of 8.3%; moderately severe leptospirosis (38.5%) with less severe organ failure and the lowest mortality rate (1.8%); and very severe leptospirosis (7%) manifested by neurological, respiratory and cardiovascular failure, with a mortality of 30%. CONCLUSIONS/SIGNIFICANCE: The outcomes of severe leptospirosis requiring ICU admission did not differ between tropical and temperate regions with similar healthcare access, practices, and resources, despite some differences in patient characteristics. The identification of three different clinical phenotypes may assist in the early diagnosis and management of severe leptospirosis.

Influence of socio-economic status on functional recovery after ARDS caused by SARS-CoV-2: the multicentre, observational RECOVIDS study.

PURPOSE: Survivors after acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19) are at high risk of developing respiratory sequelae and functional impairment. The healthcare crisis caused by the pandemic hit socially disadvantaged populations. We aimed to evaluate the influence of socio-economic status on respiratory sequelae after COVID-19 ARDS. METHODS: We carried out a prospective multicenter study in 30 French intensive care units (ICUs), where ARDS survivors were pre-enrolled if they fulfilled the Berlin ARDS criteria. For patients receiving high flow oxygen therapy, a flow ≥ 50 l/min and an FiO2 ≥ 50% were required for enrollment. Socio-economic deprivation was defined by an EPICES (Evaluation de la Précarité et des Inégalités de santé dans les Centres d'Examens de Santé - Evaluation of Deprivation and Inequalities in Health Examination Centres) score ≥ 30.17 and patients were included if they performed the 6-month evaluation. The primary outcome was respiratory sequelae 6 months after ICU discharge, defined by at least one of the following criteria: forced vital capacity < 80% of theoretical value, diffusing capacity of the lung for carbon monoxide < 80% of theoretical value, oxygen desaturation during a 6-min walk test and fibrotic-like findings on chest computed tomography. RESULTS: Among 401 analyzable patients, 160 (40%) were socio-economically deprived and 241 (60%) non-deprived; 319 (80%) patients had respiratory sequelae 6 months after ICU discharge (81% vs 78%, deprived vs non-deprived, respectively). No significant effect of socio-economic status was identified on lung sequelae (odds ratio (OR), 1.19 [95% confidence interval (CI), 0.72-1.97]), even after adjustment for age, sex, most invasive respiratory support, obesity, most severe P/F ratio (adjusted OR, 1.02 [95% CI 0.57-1.83]). CONCLUSIONS: In COVID-19 ARDS survivors, socio-economic status had no significant influence on respiratory sequelae 6 months after ICU discharge.

Influence of socioeconomic status on functional recovery after ARDS caused by SARS-CoV-2: a multicentre, observational study.

INTRODUCTION: Prognosis of patients with COVID-19 depends on the severity of the pulmonary affection. The most severe cases may progress to acute respiratory distress syndrome (ARDS), which is associated with a risk of long-term repercussions on respiratory function and neuromuscular outcomes. The functional repercussions of severe forms of COVID-19 may have a major impact on quality of life, and impair the ability to return to work or exercise. Social inequalities in healthcare may influence prognosis, with socially vulnerable individuals more likely to develop severe forms of disease. We describe here the protocol for a prospective, multicentre study that aims to investigate the influence of social vulnerability on functional recovery in patients who were hospitalised in intensive care for ARDS caused by COVID-19. This study will also include an embedded qualitative study that aims to describe facilitators and barriers to compliance with rehabilitation, describe patients' health practices and identify social representations of health, disease and care. METHODS AND ANALYSIS: The "Functional Recovery From Acute Respiratory Distress Syndrome (ARDS) Due to COVID-19: Influence of Socio-Economic Status" (RECOVIDS) study is a mixed-methods, observational, multicentre cohort study performed during the routine follow-up of post-intensive care unit (ICU) functional recovery after ARDS. All patients admitted to a participating ICU for PCR-proven SARS-CoV-2 infection and who underwent chest CT scan at the initial phase AND who received respiratory support (mechanical or not) or high-flow nasal oxygen, AND had ARDS diagnosed by the Berlin criteria will be eligible. The primary outcome is the presence of lung sequelae at 6 months after ICU discharge, defined either by alterations on pulmonary function tests, oxygen desaturation during a standardised 6 min walk test or fibrosis-like pulmonary findings on chest CT. Patients will be considered to be socially disadvantaged if they have an "Evaluation de la Précarité et des Inégalités de santé dans les Centres d'Examen de Santé" (EPICES) score ≥30.17 at inclusion. ETHICS AND DISSEMINATION: The study protocol and the informed consent form were approved by an independent ethics committee (Comité de Protection des Personnes Sud Méditerranée II) on 10 July 2020 (2020-A02014-35). All patients will provide informed consent before participation. Findings will be published in peer-reviewed journals and presented at national and international congresses. TRIAL REGISTRATION NUMBER: NCT04556513.

Alcohol withdrawal syndrome in ICU patients: Clinical features, management, and outcome predictors.

BACKGROUND: Alcohol withdrawal syndrome (AWS) is a common condition in hospitalized patients, yet its epidemiology in the ICU remains poorly characterized. METHODS: Retrospective cohort of patients admitted to the Nantes University Hospital ICU between January 1, 2017, and December 31, 2019, and coded for AWS using ICD-10 criteria. The objective of the study was to identify factors associated with complicated hospital stay defined as ICU length of stay ≥7 days or hospital mortality. RESULTS: Among 5,641 patients admitted to the ICU during the study period, 246 (4.4%) were coded as having AWS. Among them, 42 had exclusion criteria and 204 were included in the study. The three main reasons for ICU admission were sepsis (29.9%), altered consciousness (29.4%), and seizures (24%). At ICU admission, median Cushman's score was 6 [4-9] and median SOFA score was 3 [2-6]. Delirium tremens occurred in half the patients, seizures in one fifth and pneumonia in one third. Overall, 48% of patients developed complicated hospital stay, of whom 92.8% stayed in the ICU for ≥7 days, 36.7% received MV for ≥7 days, and 16.3% died during hospital stay. By multivariable analysis, two factors were associated with complicated hospital stay: a higher number of organ dysfunctions at ICU admission was associated with a higher risk of complicated hospital stay (OR, 1.18; 95CI, 1.05-1.32, P = 0.005), whereas ICU admission for seizures was associated with a lower risk of complicated hospital stay (OR, 0.14; 95%CI, 0.026-0.80; P = 0.026). CONCLUSIONS: AWS in ICU patients chiefly affects young adults and is often associated with additional factors such as sepsis, trauma, or surgery. Half the patients experienced an extended ICU stay or death during the hospital stay. The likelihood of developing complicated hospital stay relied on the reason for ICU admission and the number of organ dysfunctions at ICU admission.

Acute cholangitis in intensive care units: clinical, biological, microbiological spectrum and risk factors for mortality: a multicenter study.

BACKGROUND: Little is known on the outcome and risk factors for mortality of patients admitted in Intensive Care units (ICUs) for Acute cholangitis (AC). METHODS: Retrospective multicenter study included adults admitted in eleven intensive care units for a proven AC from 2005 to 2018. Risk factors for in-hospital mortality were identified using multivariate analysis. RESULTS: Overall, 382 patients were included, in-hospital mortality was 29%. SOFA score at admission was 8 [5-11]. Biliary obstruction was mainly related to gallstone (53%) and cancer (22%). Median total bilirubin and PCT were respectively 83 µmol/L [50-147] and 19.1 µg/L [5.3-54.8]. Sixty-three percent of patients (n = 252) had positive blood culture, mainly Gram-negative bacilli (86%) and 14% produced extended spectrum beta lactamase bacteria. At ICU admission, persisting obstruction was frequent (79%) and biliary decompression was performed using therapeutic endoscopic retrograde cholangiopancreatography (76%) and percutaneous transhepatic biliary drainage (21%). Adjusted mortality significantly decreased overtime, adjusted OR for mortality per year was 0.72 [0.54-0.96] (p = 0.02). In a multivariate analysis, factors at admission associated with in-hospital mortality were: SOFA score (OR 1.14 [95% CI 1.05-1.24] by point, p = 0.001), lactate (OR 1.21 [95% CI 1.08-1.36], by 1 mmol/L, p < 0.001), total serum bilirubin (OR 1.26 [95% CI 1.12-1.41], by 50 µmol/L, p < 0.001), obstruction non-related to gallstones (p < 0.05) and AC complications (OR 2.74 [95% CI 1.45-5.17], p = 0.002). Time between ICU admission and biliary decompression > 48 h was associated with in-hospital mortality (adjusted OR 2.73 [95% CI 1.30-6.22], p = 0.02). CONCLUSIONS: In this large retrospective multicenter study, we found that AC-associated mortality significantly decreased overtime. Severity of organ failure, cause of obstruction and local complications of AC are risk factors for mortality, as well as delayed biliary drainage > 48 h.

NSE as a predictor of death or poor neurological outcome after non-shockable cardiac arrest due to any cause: Ancillary study of HYPERION trial data.

PURPOSE: Prognostication of hypoxic-ischaemic brain injury after resuscitation from cardiac arrest is based on a multimodal approach including biomarker assays. Our goal was to assess whether plasma NSE helps to predict day-90 death or poor neurological outcome in patients resuscitated from cardiac arrest in non-shockable rhythm. METHODS: All included patients participated in the randomised multicentre HYPERION trial. Serum blood samples were taken 24, 48, and 72 h after randomisation; pre-treated, aliquoted, and frozen at -80 °C at the study sites; and shipped to a central biology laboratory, where the NSE assays were performed. Primary outcome was neurological status at day 90 assessed by Cerebral Performance Category (1 or 2 versus. 3, 4 or 5). RESULTS: NSE was assayed in 235 assessable blood samples from 101 patients. In patients with good versus poor outcomes, median NSE values at 24, 48, and 72 h were 22.6 [95%CI, 14.6;27.3] ng/mL versus 33.6 [20.5;90.0] ng/mL (p < 0.04), 18.1 [11.7;29.7] ng/mL versus 76.8 [21.5;206.6] ng/mL (p < 0.0029), and 9 [6.1;18.6] ng/mL versus 80.5 [22.9;236.1] ng/mL (p < 0.001), respectively. NSE at 48 and 72 h predicted the neurological outcome with areas under the receiver-operating curve of 0.79 [95%CI, 0.69;0.96] and 0.9 [0.81;0.96], respectively. NSE levels did not differ significantly between the groups managed at 33°C and 37°C (p = 0.59). CONCLUSIONS: Data from a multicentre trial on cardiac arrest with a non-shockable rhythm due to any cause confirm that NSE values at 72 h are associated with 90-day outcome. NSE levels did not differ significantly according to the targeted temperature. REGISTRATION IDENTIFIER: ClinicalTrial NCT02722473.

Severe leptospirosis in non-tropical areas: a nationwide, multicentre, retrospective study in French ICUs.

PURPOSE: To report the incidence, risk factors, clinical presentation, and outcome predictors of severe leptospirosis requiring intensive care unit (ICU) admission in a temperate zone. METHODS: LEPTOREA was a retrospective multicentre study conducted in 79 ICUs in metropolitan France. Consecutive adults admitted to the ICU for proven severe leptospirosis from January 2012 to September 2016 were included. Multiple correspondence analysis (MCA) and hierarchical classification on principal components (HCPC) were performed to distinguish different clinical phenotypes. RESULTS: The 160 included patients (0.04% of all ICU admissions) had median values of 54 years [38-65] for age, 40 [28-58] for the SAPSII, and 11 [8-14] for the SOFA score. Hospital mortality was 9% and was associated with older age; worse SOFA score and early need for endotracheal ventilation and/or renal replacement therapy; chronic alcohol abuse and worse hepatic dysfunction; confusion; and higher leucocyte count. Four phenotypes were identified: moderately severe leptospirosis (n = 34, 21%) with less organ failure and better outcomes; hepato-renal leptospirosis (n = 101, 63%) with prominent liver and kidney dysfunction; neurological leptospirosis (n = 8, 5%) with the most severe organ failures and highest mortality; and respiratory leptospirosis (n = 17, 11%) with pulmonary haemorrhage. The main risk factors for leptospirosis contamination were contact with animals, contact with river or lake water, and specific occupations. CONCLUSIONS: Severe leptospirosis was an uncommon reason for ICU admission in metropolitan France and carried a lower mortality rate than expected based on the high severity and organ-failure scores. The identification in our population of several clinical presentations may help clinicians establish an appropriate index of suspicion for severe leptospirosis.

Reversible Microvascular Hyporeactivity to Acetylcholine During Diabetic Ketoacidosis.

OBJECTIVES: Metabolic acidosis is commonly observed in critically ill patients. Experimental studies suggested that acidosis by itself could impair vascular function, but this has been poorly investigated in human. DESIGN: Prospective observational study. SETTING: Medical ICU in a tertiary teaching hospital. PATIENTS: To assess the relationship between metabolic acidosis severity and microvascular reactivity, we included adult diabetic patients admitted in ICU for ketoacidosis. Microvascular response to acetylcholine iontophoresis was measured at admission (baseline) and after correction of metabolic acidosis (24 hr). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Thirty-nine patients with diabetic ketoacidosis were included (68% male), with a median age of 43 (31-57) years. At admission, microvascular reactivity negatively correlated with acidosis severity (R = -0.53; p < 0.001). Microvascular response was strongly depressed at pH less than 7.20 (area under the curve, 1,779 [740-3,079] vs 12,944 [4,874-21,596] at pH > 7.20; p < 0.0001). In addition, acidosis severity was significantly correlated with capillary refill time (R = 0.50; p = 0.02). At H24, after rehydration and insulin infusion, clinical and biological disorders were fully corrected. After acidosis correction, microvascular reactivity increased more in patients with severe baseline acidosis (pH < 7.20) than in those with mild baseline acidosis (area under the curve, +453% [213%-1,470%] vs +121% [79%-312%]; p < 0.01). CONCLUSIONS: We identified an alteration of microvascular reactivity during metabolic acidosis in critically ill patients with diabetic ketoacidosis. Microvascular hyporeactivity recovered after acidosis correction.