Treatment Outcomes Among Patients With a Positive Candida Culture Close to Randomization Receiving Rezafungin or Caspofungin in the ReSTORE Study.

BACKGROUND: Rezafungin, a novel, once-weekly echinocandin for the treatment of candidemia and/or invasive candidiasis (IC) was non-inferior to caspofungin for Day 30 all-cause mortality (ACM) and Day 14 global cure in the Phase 3 ReSTORE trial (NCT03667690). We conducted pre-planned subgroup analyses for patients with a positive culture close to randomization in ReSTORE. METHODS: ReSTORE was a multicenter, double-blind, double-dummy, randomized trial in patients aged ≥18 years with candidemia and/or IC treated with once-weekly intravenous rezafungin (400 mg/200 mg) or once-daily intravenous caspofungin (70 mg/50 mg). This analysis comprised patients with a positive blood culture drawn between 12 hours before and 72 hours after randomization, or a positive culture from another normally sterile site sampled between 48 hours before and 72 hours after randomization. Efficacy endpoints included Day 30 ACM, Day 14 global cure rate, and Day 5 and 14 mycological response. Adverse events were evaluated. RESULTS: This analysis included 38 patients randomized to rezafungin and 46 to caspofungin. In the rezafungin and caspofungin groups, respectively: Day 30 ACM was 26.3% and 21.7% (between-group difference [95% confidence interval] 4.6% [-13.7, 23.5]); Day 14 global response was 55.3% and 50.0% (between-group difference 5.3% [-16.1, 26.0]); and Day 5 mycological eradication was 71.1% and 50.0% (between-group difference 21.1% [-0.2, 40.2]). Safety was comparable between treatments. CONCLUSIONS: These findings support the efficacy and safety of rezafungin compared with caspofungin for the treatment of candidemia and/or IC in patients with a positive culture close to randomization, with potential early treatment benefits for rezafungin.

Occurrences of post-traumatic stress disorder, anxiety, depression, and burnout syndrome in ICU staff workers after two-year of the COVID-19 pandemic: the international PSY-CO in ICU study.

PURPOSE: The present study aimed at assessing the prevalences of post-traumatic stress disorder (PTSD) (main objective), anxiety, depression, and burnout syndrome (BOS) and their associated factors in intensive care unit (ICU) staff workers in the second year of the COVID-19 pandemic. MATERIALS AND METHODS: An international cross-sectional multicenter ICU-based online survey was carried out among the ICU staff workers in 20 ICUs across 3 continents. ICUs staff workers (both caregivers and non-caregivers) were invited to complete PCL-5, HADS, and MBI questionnaires for assessing PTSD, anxiety, depression, and the different components of BOS, respectively. A personal questionnaire was used to isolate independent associated factors with these disorders. RESULTS: PCL-5, HADS, and MBI questionnaires were completed by 585, 570, and 539 responders, respectively (525 completed all questionnaires). PTSD was diagnosed in 98/585 responders (16.8%). Changing familial environment, being a non-caregiver staff worker, having not being involved in a COVID-19 patient admission, having not been provided with COVID-19-related information were associated with PTSD. Anxiety was reported in 130/570 responders (22.8%). Working in a public hospital, being a woman, being financially impacted, being a non-clinical healthcare staff member, having no theoretical or practical training on individual preventive measures, and fear of managing COVID-19 patients were associated with anxiety. Depression was reported in 50/570 responders (8.8%). Comorbidity at risk of severe COVID-19, working in a public hospital, looking after a child, being a non-caregiver staff member, having no information, and a request for moving from the unit were associated with depression. Having received no information and no adequate training for COVID-19 patient management were associated with all 3 dimensions of BOS. CONCLUSION: The present study confirmed that ICU staff workers, whether they treated COVID-19 patients or not, have a substantial prevalence of psychological disorders.

ß-D-Glucan Assay in the Cerebrospinal Fluid for the Diagnosis of Non-cryptococcal Fungal Infection of the Central Nervous System: A Retrospective Multicentric Analysis and a Comprehensive Review of the Literature.

BACKGROUND: Except for cryptococcosis, fungal infection of the central nervous system (FI-CNS) is a rare but severe complication. Clinical and radiological signs are non-specific, and the value of conventional mycological diagnosis is very low. This study aimed to assess the value of ß1,3-D-glucan (BDG) detection in the cerebrospinal fluid (CSF) of non-neonatal non-cryptococcosis patients. METHODS: Cases associated with BDG assay in the CSF performed in 3 French University Hospitals over 5 years were included. Clinical, radiological, and mycological results were used to classify the episodes as proven/highly probable, probable, excluded, and unclassified FI-CNS. Sensitivity and specificity were compared to that calculated from an exhaustive review of the literature. RESULTS: In total, 228 episodes consisting of 4, 7, 177, and 40 proven/highly probable, probable, excluded, and unclassified FI-CNS, respectively, were analysed. The sensitivity of BDG assay in CSF to diagnose proven/highly probable/probable FI-CNS ranged from 72.7% [95% confidence interval {CI}: 43.4%‒90.2%] to 100% [95% CI: 51%‒100%] in our study and was 82% in the literature. For the first time, specificity could be calculated over a large panel of pertinent controls and was found at 81.8% [95% CI: 75.3%‒86.8%]. Bacterial neurologic infections were associated with several false positive results. CONCLUSIONS: Despite its sub-optimal performance, BDG assay in the CSF should be added to the diagnostic armamentarium for FI-CNS.

How to distinguish mpox from its mimickers: An observational retrospective cohort study.

During the current global outbreak of mpox (formerly monkeypox), atypical features were frequently described outside endemic areas, raising concerns around differential diagnosis. In this study, we included 372 adult patients who had clinical signs consistent with mpox and who were screened using non-variola orthopoxvirus specific quantitative polymerase chain reaction (PCR) between 15 May and 15 November 2022 at the University Hospital Institute Méditerranée Infection, Marseille, France. At least one clinical sample was positive for 143 (38.4%) of these patients and 229 (61.6%) were negative. Clinically, patients who had mpox presented more frequently with systemic signs (69.9% vs. 31.0%, p < 10-6 ) including fever (51.0% vs. 30.1%, p < 10-3 ), myalgia (33.5% vs. 17.9%, p = 0.002), and lymphadenopathy (38.5% vs. 13.1%, p < 10-6 ). Among the patients who were negative for the non-variola orthopoxvirus, an alternative diagnosis was identified in 58 of them (25.3%), including chickenpox (n = 30, 13.1%), syphilis (n = 9, 4%), bacterial skin infection (n = 8, 3.5%), gonococcus (n = 5, 2.2%), HSV infection (n = 5, 2.2%), and histoplasmosis (n = 1, 0.4%). Overall, in the current outbreak, we show that mpox has a poorly specific clinical presentation. This reinforces the importance of microbiological confirmation. In symptomatic patients who are negative for the monkeypox virus by PCR, a broad differential diagnosis should be maintained.

Sequencing of monkeypox virus from infected patients reveals viral genomes with APOBEC3-like editing, gene inactivation, and bacterial agents of skin superinfection.

A large outbreak of Monkeypox virus (MPXV) infections has arisen in May 2022 in nonendemic countries. Here, we performed DNA metagenomics using next-generation sequencing with Illumina or Nanopore technologies for clinical samples from MPXV-infected patients diagnosed between June and July 2022. Classification of the MPXV genomes and determination of their mutational patterns were performed using Nextclade. Twenty-five samples from 25 patients were studied. A MPXV genome was obtained for 18 patients, essentially from skin lesions and rectal swabbing. All 18 genomes were classified in clade IIb, lineage B.1, and we identified four B.1 sublineages (B.1.1, B.1.10, B.1.12, B.1.14). We detected a high number of mutations (range, 64-73) relatively to a 2018 Nigerian genome (genome GenBank Accession no. NC_063383.1), which were harbored by a large part of a set of 3184 MPXV genomes of lineage B.1 recovered from GenBank and Nextstrain; and we detected 35 mutations relatively to genome ON563414.3 (a B.1 lineage reference genome). Nonsynonymous mutations occurred in genes encoding central proteins, among which transcription factors and core and envelope proteins, and included two mutations that would truncate a RNA polymerase subunit and a phospholipase d-like protein, suggesting an alternative start codon and gene inactivation, respectively. A large majority (94%) of nucleotide substitutions were G > A or C > U, suggesting the action of human APOBEC3 enzymes. Finally, >1000 reads were identified as from Staphylococcus aureus and Streptococcus pyogenes for 3 and 6 samples, respectively. These findings warrant a close genomic monitoring of MPXV to get a better picture of the genetic micro-evolution and mutational patterns of this virus, and a close clinical monitoring of skin bacterial superinfection in monkeypox patients.

Pre-Hospital Management of Patients with COVID-19 and the Impact on Hospitalization.

Background and Objectives: During the COVID-19 pandemic, patient care was mainly organized around the hospital. Pre-hospital care has, to our knowledge, never been evaluated. We aimed to study the impact of pre-hospital pathways on hospitalization during the last part of the pandemic. Materials and Methods: This was a monocentric, retrospective analysis of prospectively collected medical records. Data from patients admitted to our institute between 1 February and 7 March 2022 were analyzed. The primary outcomes were defined as the number of hospitalizations, resuscitations, and deaths at the time of interview and in the subsequent 30 days. The main explanatory variables were times from onset of symptoms to care, age, gender, News2 score, comorbidities, and pre-hospital pathways and their duration. Results: Three pre-hospital pathways were identified: a pathway in which the patient consults a general practitioner for a test (PHP1); a pathway in which the patient consults for care (PHP2); and no pre-hospital pathway and direct admission to hospital (PHP3). Factors independently associated with outcome (hospitalization) were being male (OR 95% CI; 2.21 (1.01-4.84), p = 0,04), News2 score (OR 95% CI; 2.04 (1.65-2.51), p < 0.001), obesity (OR 95% CI; 3.45 (1.48-8.09), p = 0.005), D-dimers > 0.5 µg/mL (OR 95% CI; 3.45 (1.47-8.12), p = 0.005), and prolonged time from symptoms to hospital care (PHP duration) (OR 95% CI; 1.07 (1.01-1.14), p = 0.03). All things being equal, patients with a "PHP2" pre-hospital pathway had a higher probability of hospitalization compared to those with a "PHP3" pre-hospital pathway (OR 95% CI; 4.31 (1.48-12.55), p = 0.007). Conclusions: Along with recognized risk factors such as gender, News 2 score, and obesity, the patient's pre-hospital pathway is an important risk factor associated with hospitalization.

Observational Cohort Study of Evolving Epidemiologic, Clinical, and Virologic Features of Monkeypox in Southern France.

We enrolled 136 patients with laboratory-confirmed monkeypox during June 4-August 31, 2022, at the University Hospital Institute Méditerranée Infection in Marseille, France. The median patient age was 36 years (interquartile range 31-42 years). Of 136 patients, 125 (92%) were men who have sex with men, 15 (11%) reported previous smallpox vaccinations, and 21 (15.5%) were HIV-positive. The most frequent lesion locations were the genitals (68 patients, 53%), perianal region (65 patients, 49%), and oral/perioral area (22 patients, 17%). Lesion locations largely corresponded with the route of contamination. Most (68%) patients had isolated anal, genital, or oral lesions when they were first seen, including 56 (61%) who had >1 positive site without a visible lesion. Concurrent sexually transmitted infections were diagnosed in 19 (15%) patients, and 7 patients (5%) were asymptomatic. We recommend vaccination campaigns, intensified testing for sexually transmitted infections, and increased contact tracing to control the ongoing monkeypox outbreak.

First cases of infection with the 21L/BA.2 Omicron variant in Marseille, France.

The SARS-CoV-2 21K/BA.1, 21L/BA.2, and BA.3 Omicron variants have recently emerged worldwide. To date, the 21L/BA.2 Omicron variant has remained very minority globally but became predominant in Denmark instead of the 21K/BA.1 variant. Here, we describe the first cases diagnosed with this variant in south-eastern France. We identified 13 cases using variant-specific qPCR and next-generation sequencing between 28/11/2021 and 31/01/2022, the first two cases being diagnosed in travelers returning from Tanzania. Overall, viral genomes displayed a mean (±standard deviation) number of 65.9 ± 2.5 (range, 61-69) nucleotide substitutions and 31.0 ± 8.3 (27-50) nucleotide deletions, resulting in 49.6 ± 2.2 (45-52) amino acid substitutions (including 28 in the spike protein) and 12.4 ± 1.1 (12-15) amino acid deletions. Phylogeny showed the distribution in three different clusters of these genomes, which were most closely related to genomes from England and South Africa, from Singapore and Nepal, or from France and Denmark. Structural predictions highlighted a significant enlargement and flattening of the surface of the 21L/BA.2 N-terminal domain of the spike protein compared to that of the 21K/BA.1 Omicron variant, which may facilitate initial viral interactions with lipid rafts. Close surveillance is needed at global, country, and center scales to monitor the incidence and clinical outcome of the 21L/BA.2 Omicron variant.

Early hyperoxia and 28-day mortality in patients on venoarterial ECMO support for refractory cardiogenic shock: a bicenter retrospective propensity score-weighted analysis.

BACKGROUND: The mortality rate for a patient with a refractory cardiogenic shock on venoarterial (VA) extracorporeal membrane oxygenation (ECMO) remains high, and hyperoxia might worsen this prognosis. The objective of the present study was to evaluate the association between hyperoxia and 28-day mortality in this setting. METHODS: We conducted a retrospective bicenter study in two French academic centers. The study population comprised adult patients admitted for refractory cardiogenic shock. The following arterial partial pressure of oxygen (PaO2) variables were recorded for 48 h following admission: the absolute peak PaO2 (the single highest value measured during the 48 h), the mean daily peak PaO2 (the mean of each day's peak values), the overall mean PaO2 (the mean of all values over 48 h), and the severity of hyperoxia (mild: PaO2 < 200 mmHg, moderate: PaO2 = 200-299 mmHg, severe: PaO2 ≥ 300 mmHg). The main outcome was the 28-day all-cause mortality. Inverse probability weighting (IPW) derived from propensity scores was used to reduce imbalances in baseline characteristics. RESULTS: From January 2013 to January 2020, 430 patients were included and assessed. The 28-day mortality rate was 43%. The mean daily peak, absolute peak, and overall mean PaO2 values were significantly higher in non-survivors than in survivors. In a multivariate logistic regression analysis, the mean daily peak PaO2, absolute peak PaO2, and overall mean PaO2 were independent predictors of 28-day mortality (adjusted odds ratio [95% confidence interval per 10 mmHg increment: 2.65 [1.79-6.07], 2.36 [1.67-4.82], and 2.85 [1.12-7.37], respectively). After IPW, high level of oxygen remained significantly associated with 28-day mortality (OR = 1.41 [1.01-2.08]; P = 0.041). CONCLUSIONS: High oxygen levels were associated with 28-day mortality in patients on VA-ECMO support for refractory cardiogenic shock. Our results confirm the need for large randomized controlled trials on this topic.

Individualised or liberal red blood cell transfusion after cardiac surgery: a randomised controlled trial.

BACKGROUND: Current practice guidelines for red blood cell (RBC) transfusion in ICUs are based on haemoglobin threshold, without consideration of oxygen delivery or consumption. We aimed to evaluate an individual physiological threshold-guided by central venous oxygen saturation ScvO2. METHODS: In a randomised study in two French academic hospitals, 164 patients who were admitted to ICU after cardiac surgery with postoperative haemoglobin <9 g dl-1 were randomised to receive a transfusion with one unit of RBCs (haemoglobin group) or transfusion only if the ScvO2 was <70% (individualised group). The primary outcome was the number of subjects receiving at least one unit of RBCs. The secondary composite outcome was acute kidney injury, stroke, myocardial infarction, acute heart failure, mesenteric ischaemia, or in-hospital mortality. One- and 6-month mortality were evaluated during follow-up. RESULTS: The primary outcome was observed for 80 of 80 subjects (100%) in the haemoglobin group and in 61 of 77 patients (79%) in the individualised group (absolute risk -21% [-32.0; -14.0]; P<0.001). There was no significant difference in the secondary outcome between the two groups. Follow-up showed a non-significant difference in mortality at 1 and 6 months. CONCLUSIONS: An individualised strategy based on an central venous oxygen saturation threshold of 70% allows for a more restrictive red blood cell transfusion strategy with no incidence on postoperative morbidity or 6-month mortality. CLINICAL TRIAL REGISTRATION: NCT02963883.

Origin of COVID-19: Dismissing the Mojiang mine theory and the laboratory accident narrative.

The origin of SARS-CoV-2 is still the subject of a controversial debate. The natural origin theory is confronted to the laboratory leak theory. The latter is composite and comprises contradictory theories, one being the leak of a naturally occurring virus and the other the leak of a genetically engineered virus. The laboratory leak theory is essentially based on a publication by Rahalkar and Bahulikar in 2020 linking SARS-CoV-2 to the Mojiang mine incident in 2012 during which six miners fell sick and three died. We analyzed the clinical reports. The diagnosis is not that of COVID-19 or SARS. SARS-CoV-2 was not present in the Mojiang mine. We also bring arguments against the laboratory leak narrative.

Time to source control and outcome in community-acquired intra-abdominal infections: The multicentre observational PERICOM study.

BACKGROUND: Optimal management of community-acquired intra-abdominal infections (IAI) requires timely surgical source control and adequate anti-infective treatment. OBJECTIVE: To describe the initial management of community-acquired IAI admitted to the emergency department and assess the association between the length of time to either diagnosis or therapeutic procedures and patient outcomes. DESIGN: A prospective, multicentre, observational study. SETTING: Thirteen teaching hospitals in France between April 2018 and February 2019. PATIENTS: Two hundred and five patients aged at least 18 years diagnosed with community-acquired IAI. MAIN OUTCOME MEASURES: The primary outcome was hospital length of stay. The secondary outcome was hospital mortality. RESULTS: Patients had a mean age of 56 (± 21) years and a median [interquartile] SAPS II of 26 [17 to 34]. Among the study cohort, 18% were postoperatively transferred to intensive care unit and 7% had died by day 28. Median [IQR] time to imaging, antibiotic therapy and surgery were 4 [2 to 6], 7.5 [4 to 12.5] and 9 [5.5 to 17] hours, respectively. The length of time to surgical source control [0.99, 95% confidence interval (CI), 0.98 to 0.99], SOFA greater than 2 [0.36 (95% CI, 0.26 to 0.651)], age greater than 60 years [0.65 (95% CI, 0.45 to 0.94)], generalized peritonitis [0.7 (95% CI, 0.56 to 0.89)] and laparotomy surgery [0.657 (95% CI, 0.42 to 0.78)] were associated with longer hospital length of stay. The duration of time to surgical source control [1.02 (95% CI, 1.01 to 1.04)], generalized peritonitis [2.41 (95% CI, 1.27 to 4.61)], and SOFA score greater than 2 [6.14 (95% CI, 1.40 to 26.88)] were identified as independent risk factors for 28-day mortality. CONCLUSION: This multicentre observational study revealed that the time to surgical source control, patient severity and generalized peritonitis were identified as independent risk factors for increased hospital LOS and mortality in community-acquired IAI. Organisational strategies to reduce the time to surgical management of intra-abdominal infections should be further evaluated. STUDY REGISTRATION: ClinicalTrials.gov on 1 April 2018, NCT03544203.

Multinational Observational Cohort Study of COVID-19-Associated Pulmonary Aspergillosis1.

We performed an observational study to investigate intensive care unit incidence, risk factors, and outcomes of coronavirus disease-associated pulmonary aspergillosis (CAPA). We found 10%-15% CAPA incidence among 823 patients in 2 cohorts. Several factors were independently associated with CAPA in 1 cohort and mortality rates were 43%-52%.

Risk factors for therapeutic failure in the management of post-operative peritonitis: a post hoc analysis of the DURAPOP trial.

BACKGROUND: Therapeutic failure is a frequent issue in the management of post-operative peritonitis. OBJECTIVES: A post hoc analysis of the prospective, multicentre DURAPOP trial analysed the risk factors for failures in post-operative peritonitis following adequate source control and empirical antibiotic therapy in critically ill patients. PATIENTS AND METHODS: Overall failures assessed post-operatively between Day 8 and Day 45 were defined as a composite of death and/or surgical and/or microbiological failures. Risk factors for failures were assessed using logistic regression analyses. RESULTS: Among the 236 analysed patients, overall failures were reported in 141 (59.7%) patients, including 30 (12.7%) deaths, 81 (34.3%) surgical and 95 (40.2%) microbiological failures. In the multivariate analysis, the risk factors associated with overall failures were documented piperacillin/tazobactam therapy [adjusted OR (aOR) 2.10; 95% CI 1.17-3.75] and renal replacement therapy on the day of reoperation (aOR 2.96; 95% CI 1.05-8.34). The risk factors for death were age (aOR 1.08 per year; 95% CI 1.03-1.12), renal replacement therapy on reoperation (aOR 3.95; 95% CI 1.36-11.49) and diabetes (OR 6.95; 95% CI 1.34-36.03). The risk factors associated with surgical failure were documented piperacillin/tazobactam therapy (aOR 1.99; 95% CI 1.13-3.51), peritoneal cultures containing Klebsiella spp. (aOR 2.45; 95% CI 1.02-5.88) and pancreatic source of infection (aOR 2.91; 95% CI 1.21-7.01). No specific risk factors were identified for microbiological failure. CONCLUSIONS: Our data suggest a predominant role of comorbidities, the severity of post-operative peritonitis and possibly of documented piperacillin/tazobactam treatment on the occurrence of therapeutic failures, regardless of their type.

The association between body mass index class and coronavirus disease 2019 outcomes.

BACKGROUND/OBJECTIVES: A growing body of data suggests that obesity influences coronavirus disease 2019 (COVID-19). Our study's primary objective was to assess the association between body mass index (BMI) categories and critical forms of COVID-19. SUBJECTS/METHODS: Data on consecutive adult patients hospitalized with laboratory-confirmed COVID-19 at Amiens University Hospital (Amiens, France) were extracted retrospectively. The association between BMI categories and the composite primary endpoint (admission to the intensive care unit or death) was probed in a logistic regression analysis. RESULTS: In total, 433 patients were included, and BMI data were available for 329: 20 were underweight (6.1%), 95 have a normal weight (28.9%), 90 were overweight (27.4%), and 124 were obese (37.7%). The BMI category was associated with the primary endpoint in the fully adjusted model; the odds ratio (OR) [95% confidence interval (CI)] for overweight and obesity were respectively 1.58 [0.77-3.24] and 2.58 [1.28-5.31]. The ORs [95% CI] for ICU admission were similar for overweight (3.16 [1.29-8.06]) and obesity (3.05 [1.25-7.82]) in the fully adjusted model. The unadjusted ORs for death were similar in all BMI categories while obesity only was associated with higher risk after adjustment. CONCLUSIONS: Our results suggest that overweight (and not only obesity) is associated with ICU admission, but overweight is not associated with death.

Early combination therapy with hydroxychloroquine and azithromycin reduces mortality in 10,429 COVID-19 outpatients.

We evaluated the age-specific mortality of unselected adult outpatients infected with SARS-CoV-2 treated early in a dedicated COVID-19 day hospital and we assessed whether the use of hydroxychloroquine (HCQ) + azithromycin (AZ) was associated with improved survival in this cohort. A retrospective monocentric cohort study was conducted in the day hospital of our center from March to December 2020 in adults with PCR-proven infection who were treated as outpatients with a standardized protocol. The primary endpoint was 6-week mortality, and secondary endpoints were transfer to the intensive care unit and hospitalization rate. Among 10,429 patients (median age, 45 [IQR 32-57] years; 5597 [53.7%] women), 16 died (0.15%). The infection fatality rate was 0.06% among the 8315 patients treated with HCQ+AZ. No deaths occurred among the 8414 patients younger than 60 years. Older age and male sex were associated with a higher risk of death, ICU transfer, and hospitalization. Treatment with HCQ+AZ (0.17 [0.06-0.48]) was associated with a lower risk of death, independently of age, sex and epidemic period. Meta-analysis evidenced consistency with 4 previous outpatient studies (32,124 patients-Odds ratio 0.31 [0.20-0.47], I2 = 0%). Early ambulatory treatment of COVID-19 with HCQ+AZ as a standard of care is associated with very low mortality, and HCQ+AZ improve COVID-19 survival compared to other regimens.

Characteristics and outcomes of COVID-19 in hospitalized patients with and without diabetes.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a rapidly progressing pandemic, with four million confirmed cases and 280 000 deaths at the time of writing. Some studies have suggested that diabetes is associated with a greater risk of developing severe forms of COVID-19. The primary objective of the present study was to compare the clinical features and outcomes in hospitalized COVID-19 patients with vs without diabetes. METHODS: All consecutive adult patients admitted to Amiens University Hospital (Amiens, France) with confirmed COVID-19 up until April 21st, 2020, were included. The composite primary endpoint comprised admission to the intensive care unit (ICU) and death. Both components were also analysed separately in a logistic regression analysis and a Cox proportional hazards model. RESULTS: A total of 433 patients (median age: 72; 238 (55%) men; diabetes: 115 (26.6%)) were included. Most of the deaths occurred in non-ICU units and among older adults. Multivariate analyses showed that diabetes was associated neither with the primary endpoint (odds ratio (OR): 1.12; 95% confidence interval (CI): 0.66-1.90) nor with mortality (hazard ratio: 0.73; 95%CI: 0.40-1.34) but was associated with ICU admission (OR: 2.06; 95%CI 1.09-3.92, P = .027) and a longer length of hospital stay. Age was negatively associated with ICU admission and positively associated with death. CONCLUSIONS: Diabetes was prevalent in a quarter of the patients hospitalized with COVID-19; it was associated with a greater risk of ICU admission but not with a significant elevation in mortality. Further investigation of the relationship between COVID-19 severity and diabetes is warranted.

Invasive Tracheobronchial Aspergillosis in Critically Ill Patients with Severe Influenza. A Clinical Trial.

Rationale: Invasive tracheobronchial aspergillosis (ITBA) is an uncommon but severe clinical form of invasive pulmonary aspergillosis in which the fungal infection is entirely or predominantly confined to the tracheobronchial tree.Objectives: To analyze the diagnostic and prognostic differences between tracheobronchial aspergillosis and pulmonary aspergillosis without tracheobronchial lesions among patients admitted to the ICU with severe influenza.Methods: This retrospective, observational study included critically ill patients with influenza associated with pulmonary aspergillosis from three hospital ICUs between 2010 and 2019. Patient characteristics and clinical and mycologic data at admission and during ICU stay were collected in a database to evaluate variables in the two groups.Measurements and Main Results: Thirty-five patients admitted to the ICU with severe influenza and pulmonary aspergillosis were included. Ten patients were included in the group with ITBA (n = 10 of 35; 28.6%), and 25 patients were included in the group without ITBA. The group with ITBA comprised more patients with active smoking, diabetes mellitus, and higher severity scores (Simplified Acute Physiology Score II). Ninety-day mortality rates in the groups with and without ITBA were 90% and 44%, respectively (P = 0.02). Moreover, significantly higher serum 1,3-ß-d-glucan and galactomannan and BAL fluid galactomannan concentrations were observed in the group with ITBA compared with the group without ITBA (P < 0.0001, P = 0.003, and P = 0.008, respectively).Conclusions: ITBA was associated with higher severity scores, mortality, and serum and BAL fluid galactomannan and 1,3-ß-d-glucan concentrations than invasive pulmonary aspergillosis without tracheobronchial lesions. ITBA should be systematically researched by bronchoscopic examination in ICU patients with concomitant pulmonary aspergillosis and influenza.Clinical trial registered with www.clinicaltrials.gov (NCT04077697).

Central venous-to-arterial CO2 difference is a poor tool to predict adverse outcomes after cardiac surgery: a retrospective study.

PURPOSE: The venous-to-arterial carbon dioxide partial pressure difference (CO2 gap) has been reported to be a sensitive indicator of cardiac output adequacy. We aimed to assess whether the CO2 gap can predict postoperative adverse outcomes after cardiac surgery. METHODS: A retrospective study was conducted of 5,151 patients from our departmental database who underwent cardiac surgery from 1 January 2008 to 31 December 2018. Lactate level (mmol·L-1), central venous oxygen saturation (ScVO2) (%), and the venous-to-arterial carbon dioxide difference (CO2 gap) were measured at intensive care unit (ICU) admission and on days 1 and 2 after cardiac surgery. The following postoperative adverse outcomes were collected: ICU mortality, hemopericardium or tamponade, resuscitated cardiac arrest, acute kidney injury, major bleeding, acute hepatic failure, mesenteric ischemia, and pneumonia. The primary outcome was the presence of at least one postoperative adverse outcome. Logistic regression was used to assess the association between ScVO2, lactate, and the CO2 gap with adverse outcomes. Their diagnostic performance was compared using a receiver operating characteristic (ROC) curve. RESULTS: There were 1,933 patients (38%) with an adverse outcome. Cardiopulmonary bypass (CPB) parameters were similar between groups. The CO2 gap was slightly higher for the "adverse outcomes" group than for the "no adverse outcomes" group. Arterial lactate at admission, day 1, and day 2 was also slightly higher in patients with adverse outcomes. Central venous oxygen saturation was not significantly different between patients with and without adverse outcomes. The area under the ROC curve to predict outcomes after CPB for the CO2 gap at admission, day 1, and day 2 were 0.52, 0.55, and 0.53, respectively. CONCLUSION: After cardiac surgery with CPB, the CO2 gap at ICU admission, day 1, and day 2 was associated with postoperative adverse outcomes but showed poor diagnostic performance.

RéSUMé: OBJECTIF: La différence de pression partielle de dioxyde de carbone veineux versus artériel (gradient de CO2) a été rapportée comme étant un indicateur sensible d'un débit cardiaque adéquat. Nous avons tenté d'évaluer si le gradient de CO2 pouvait prédire les devenirs postopératoires défavorables après une chirurgie cardiaque. MéTHODE: Une étude rétrospective a été réalisée en se basant sur les dossiers de 5151 patients issus de notre base de données départementale ayant subi une chirurgie cardiaque entre le 1er janvier 2008 et le 31 décembre 2018. Les taux de lactate (mmol·L−1), la saturation en oxygène veineux central (ScVO2) (%), et la différence de dioxyde de carbone veineux versus artériel (gradient de CO2) ont été mesurés lors de l'admission en réanimation (ICU) et aux jours 1 et 2 après la chirurgie cardiaque. Les complications postopératoires suivantes ont été colligées : mortalité en réanimation, hémopéricarde ou tamponnade, arrêt cardiaque récupéré, insuffisance rénale aiguë, saignements majeurs, insuffisance hépatique aiguë, ischémie mésentérique et pneumonie. Le critère d'évaluation principal était la présence d'au moins une complication postopératoire. La régression logistique a été utilisée pour évaluer l'association entre ScVO2, taux de lactate et gradient de CO2 et les complications. Leur performance diagnostique a été comparée à l'aide d'une courbe ROC (receiver operating characteristic). RéSULTATS: Des complications sont survenues chez 1933 patients (38 %). Les paramètres de circulation extracorporelle (CEC) étaient semblables entre les groupes. Le gradient de CO2 était légèrement plus élevé dans le groupe « complications ¼ que dans le groupe « pas de complication ¼. Les taux de lactate artériels à l'admission, au jour 1 et au jour 2 étaient également légèrement plus élevés chez les patients ayant subi des complications. La différence de saturation en oxygène veineux central n'était pas significative entre les patients avec ou sans complications. L'aire sous la courbe ROC pour prédire les devenirs après la CEC pour le gradient de CO2 à l'admission, au jour 1 et au jour 2 était de 0,52, 0,55 et 0,53, respectivement. CONCLUSION: Après une chirurgie cardiaque avec CEC, le gradient de CO2 à l'admission en réanimation, au jour 1 et au jour 2 était associé aux complications postopératoires, mais sa performance diagnostique était médiocre.

Changes in Plasma Angiopoietin Levels After Transcatheter Aortic Valve Replacement and Surgical Aortic Valve Replacement: A Prospective Cohort Study.

OBJECTIVE: Angiopoietins (Angs) regulate endothelial permeability. Ang-1 and 2 (Ang-1 and Ang-2) are implied in endothelial stability through an antagonism effect. The objectives of the present study were to describe and compare changes in Ang levels after transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR). DESIGN: A prospective, single-center study. PARTICIPANTS: Adult patients with aortic stenosis scheduled for SAVR or TAVR. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Ang-1 and Ang-2 were measured using an enzyme-linked immunosorbent assay right before surgery (T0), at the end of surgery (T1), and at day one (T2). Sixty consecutive patients (SAVR group [n = 30] and TAVR group [n = 30]) were included between January and June 2017. Ang-1 decreased significantly after both TAVR (T0: 3,663 [2,602-4,262]; T1: 1,611 [981-2,409]; T2: 1,082 [652-1,589] ng/mL; p < 0.0001) and SAVR (T0: 1,603 [975-2,849]; T1: 783 [547-1,024]; T2: 828 [460-1,227] ng/mL; p = 0.0001). Ang-2 increased significantly after SAVR (T0: 2,472 [1,502-3,622]; T1: 2,997 [1,759-3,839]; T2: 5,421 [3,557-7,087] ng/mL; p < 0.0001) but did not change markedly after TAVR (T0: 3,343 [2,661-6,272]; T1: 3,788 [2,574-5,016]; T2: 3,446 [3,029-6,313] ng/mL; p = 0.066). Among patients with paravalvular leakage, the changes in the plasma Ang-2 level and the Ang-2/Ang-1 ratio were greater. CONCLUSION: SAVR induces greater alterations of Ang homeostasis than TAVR, confirming a role for the use of cardiopulmonary bypass. Paravalvular leakage after TAVR is associated with Ang changes similar to those observed with SAVR.