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PurposeThe SARS-CoV-2 infection can lead to a severe acute respiratory distress syndrome (ARDS) with prolonged mechanical ventilation and high mortality rate. Interestingly, COVID-19-associated ARDS share biological and clinical features with sepsis-associated immunosuppression since lymphopenia and acquired infections associated with late mortality are frequently encountered. Mechanisms responsible for COVID-19-associated lymphopenia need to be explored since they could be responsible for delayed virus clearance and increased mortality rate among intensive care unit (ICU) patients.MethodsA series of 26 clinically annotated COVID-19 patients were analyzed by thorough phenotypic and functional investigations at days 0, 4, and 7 after ICU admission.ResultsWe revealed that, in the absence of any difference in demographic parameters nor medical history between the two groups, ARDS patients presented with an increased number of myeloid-derived suppressor cells (MDSC) and a decreased number of CD8pos effector memory cell compared to patients hospitalized for COVID-19 moderate pneumonia. Interestingly, COVID-19-related MDSC expansion was directly correlated to lymphopenia and enhanced arginase activity. Lastly, T cell proliferative capacity in vitro was significantly reduced among COVID-19 patients and could be restored through arginine supplementation.ConclusionsThe present study reports a critical role for MDSC in COVID-19-associated ARDS. Our findings open the possibility of arginine supplementation as an adjuvant therapy for these ICU patients, aiming to reduce immunosuppression and help virus clearance, thereby decreasing the duration of mechanical ventilation, nosocomial infection acquisition, and mortality.

The purpose of this study is to assess risk factors for the acquisition of extended-spectrum β-lactamase-producing Gram-negative bacilli (ESBL-GNB) colonization and infection (AI) in ICUs with low ESBL-GNB prevalence rate. We conducted a retrospective observational study in three ICUs in Bretagne, France. All patients admitted from January 2016 to September 2017 with a length of stay of 2 days or more were included. Universal screening for ESBL-GNB colonization was performed in all participating ICUs. Of the 3250 included patients, 131 (4.0%) were colonized at admission, 59 acquired colonization while hospitalized (1.9%; 95% CI [1.5–2.5%]), and 15 (0.5%; 95% CI [0.3–0.8%]) acquired ESBL-GNB infections. In the case of infection, the specificity and the negative predictive values of preexistent colonization for the ESBL-GNB etiology were 93.2% [91.5–95.1%] and 95.2% [93.5–97.1%], respectively. Colonization was the main risk factor for ESBL-GNB AI (OR = 9.61; 95% CI [2.86–32.29]; p < 0.001). Antimicrobial susceptibility of non-ESBL-GNB isolates responsible for AI was similar for any non-carbapenem β-lactam (95%) and imipenem (94%). ESBL-GNB AIs were rare in ICUs with low ESBL-GNB prevalence rate. Prior colonization was the main risk factor for subsequent infection. Empirical carbapenem therapy could be avoided in non ESBL-GNB colonized patients with suspected AI.

BackgroundIncreasing use of cardiovascular implantable electronic devices (CIED), as permanent pacemakers (PPM), implantable cardioverter defibrillators (ICD), or cardiac resynchronization therapy (CRT), is associated with the emergence of CIED-related infective endocarditis (CIED-IE). We aimed to characterize CIED-IE profile, temporal trends, and prognostic factors.MethodsCIED-IE diagnosed at Rennes University Hospital during years 1992–2017 were identified through computerized database, and included if they presented all of the following: (1) clinical signs of infection; (2) microbiological documentation through blood and/or CIED lead cultures; (3) lead or valve vegetation, or definite IE according to Duke criteria. Data were retrospectively extracted from medical charts. The cohort was categorized in three periods: 1992–1999, 2000–2008, and 2009–2017.ResultsWe included 199 patients (51 women, 148 men, median age 73 years [interquartile range, 64–79]), with CIED-IE: 158 PPMs (79%), 24 ICD (12%), and 17 CRT (9%). Main pathogens were coagulase-negative staphylococci (CoNS: n = 86, 43%), Staphylococcus aureus (n = 60, 30%), and other Gram-positive cocci (n = 28, 14%). Temporal trends were remarkable for the decline in CoNS (P = 0.002), and the emergence of S. aureus as the primary cause of CIED-IE (24/63 in 2009–2017, 38%). Factors independently associated with one-year mortality were chronic obstructive pulmonary disease (COPD: hazard ratio 3.84 [1.03–6.02], P = 0.03), left-sided endocarditis (HR 2.25 [1.09–4.65], P = 0.03), pathogens other than CoNS (HR 3.16 [1.19–8.39], P = 0.02), and CIED removal/reimplantation (HR 0.41 [0.20–0.83], P = 0.01).ConclusionsS. aureus has emerged as the primary cause of CIED-IE. Left-sided endocarditis, COPD, pathogens other than CoNS, and no CIED removal/reimplantation are independent risk factors for one-year mortality.

Background and Aim The molecular adsorbent recirculating system (MARS) is the most widely used device to treat liver failure. Nevertheless, data from widespread real‐life use are lacking. Methods This was a retrospective multicenter study conducted in all French adult care centers that used MARS between 2004 and 2009. The primary objective was to evaluate patient survival according to the liver disease and listing status. Factors associated with mortality were the secondary objectives. Results A total of 383 patients underwent 393 MARS treatments. The main indications were acute liver failure (ALF, 32.6%), and severe cholestasis (total bilirubin >340 μmol/L) (37.2%), hepatic encephalopathy (23.7%), and/or acute kidney injury–hepatorenal syndrome (22.9%) most often among patients with chronic liver disease. At the time of treatment, 34.4% of the patients were listed. Overall, the hospital survival rate was 49% (95% CI: 44–54%) and ranged from 25% to 81% depending on the diagnosis of the liver disease. In listed patients versus those not listed, the 1‐year survival rate was markedly better in the setting of nonbiliary cirrhosis (59% vs 15%), early graft nonfunction (80% vs 0%), and late graft dysfunction (72% vs 0%) (all P < 0.001). Among nonbiliary cirrhotic patients, hospital mortality was associated with the severity of liver disease (HE and severe cholestasis) and not being listed for transplant. In ALF, paracetamol etiology and ≥3 MARS sessions were associated with better transplant‐free survival. Conclusion Our study suggests that MARS should be mainly used as a bridge to liver transplantation. Survival was correlated with being listed for most etiologies and with the intensity of treatment in ALF. Because the long‐term outcome of patients treated with the molecular adsorbent recirculating system (MARS) in the real life has not been well assessed, we performed a retrospective multicenter study in all French adult care centers that used MARS between 2004 and 2009. The hospital survival rate was 49% (95% CI: 44–54%) and varied from 25% to 81% depending on the diagnosis of the liver disease and the 1‐year survival rate was markedly better in listed versus not listed patients in the setting of non‐biliary cirrhosis (59% vs 15%), early graft non‐function (80% vs 0%) and late graft dysfunction (72% vs 0%) (all P < 0.001). In acute liver failure, paracetamol etiology and ≥3 MARS sessions were associated with higher transplant‐free survival.

Purpose CD64 expression on the surface of neutrophils has recently been proposed as an early marker of bacterial infection. The goal of this study was to determine whether the CD64 index allows differentiation of bacterial sepsis from viral and fungal sepsis and other inflammatory states in a critical-care setting. Methods This was an observational prospective study conducted in a medical ICU of a university hospital. All patients admitted between September 2009 and March 2010 with at least two criteria for systemic inflammatory response syndrome (SIRS) were eligible for inclusion. Upon admission, hematological exams were conducted by flow cytometry, allowing quantification of CD64 expression (Leuko64™ kit, Trillium Diagnostics LLC, USA). ROC curve analysis was performed to evaluate the utility of the CD64 index in the diagnosis of bacterial infection. Patients with suspected infection were excluded when infection could not be microbiologically confirmed. Results Our study included 293 patients with a SAPS II score of 45 (31–59). Bacterial infection was found in 148 patients and SIRS or non-bacterial infection was documented in 145 patients. A CD64 index greater than 2.2 predicted bacterial infection with a sensitivity and specificity of 63% (55–71%) and 89% (83–94%), respectively. The area under the ROC curve was 0.8 (0.75–0.84). Positive and negative likelihood ratios were 5.7 (5.0–6.5) and 0.4 (0.3–0.7), respectively. Conclusions The CD64 index is specific for bacterial infection among ICU patients. As a result of its weak sensitivity, the CD64 index may not be practically recommended, but it may be useful in combination with a more sensitive biological marker.

Background Vacuoles, E1 enzyme, X-linked, autoinflammatory, and somatic syndrome is a newly discovered inflammatory disease affecting male subjects, for which few data exist in the literature. Here, we describe the case of a patient with known Sweet’s syndrome admitted to the intensive care unit and for whom a vacuoles, E1 enzyme, X-linked, autoinflammatory, and somatic syndrome was diagnosed, allowing for appropriate treatment and the patient’s discharge and recovery. Case presentation A 70-year-old male White patient was hospitalized in the intensive care unit following an intrahospital cardiac arrest. History started a year before with repeated deep vein thrombosis and episodes of skin eruption compatible with Sweet’s syndrome. After a course of oral steroids, fever and inflammatory syndrome relapsed with onset of polychondritis, episcleritis along with neurological symptoms and pulmonary infiltrates. Intrahospital hypoxic cardiac arrest happened during patient’s new investigations, and he was admitted in a critical state. During the intensive care unit stay, he presented with livedoid skin lesions on both feet. Vasculitis was not proven; however, cryoglobulinemia screening came back positive. Onset of pancytopenia was explored with a myelogram aspirate. It showed signs of dysmyelopoiesis and vacuoles in erythroid and myeloid precursors. Of note, new deep vein thrombosis developed, despite being treated with heparin leading to the diagnosis of heparin-induced thrombocytopenia. The course of symptoms were overlapping multiple entities, and so a multidisciplinary team discussion was implemented. Screening for UBA1 -mutation in the blood came back positive, confirming the vacuoles, E1 enzyme, X-linked, autoinflammatory, and somatic syndrome. Corticosteroids and anti-IL1 infusion were started with satisfactory results supporting patient’s discharge from intensive care unit to the internal medicine ward. Conclusions Vacuoles, E1 enzyme, X-linked, autoinflammatory, and somatic syndrome should be suspected in male patients presenting with inflammatory symptoms, such as fever, skin eruption, chondritis, venous thromboembolism, and vacuoles in bone marrow precursors. Patients with undiagnosed vacuoles, E1 enzyme, X-linked, autoinflammatory, and somatic syndrome may present with organ failure requiring hospitalization in intensive care unit, where screening for UBA1 mutation should be performed when medical history is evocative. Multidisciplinary team involvement is highly recommended for patient management, notably to start appropriate immunosuppressive treatments.

Large studies on severe imported malaria in non-endemic industrialized countries are lacking. We sought to describe the clinical spectrum of severe imported malaria in French adults and to identify risk factors for mortality at admission to the intensive care unit. Retrospective review of severe Plasmodium falciparum malaria episodes according to the 2000 World Health Organization definition and requiring admission to the intensive care unit. Data were collected from medical charts using standardised case-report forms, in 45 French intensive care units in 2000-2006. Risk factors for in-hospital mortality were identified by univariate and multivariate analyses. Data from 400 adults admitted to the intensive care unit were analysed, representing the largest series of severe imported malaria to date. Median age was 45 years; 60% of patients were white, 96% acquired the disease in sub-Saharan Africa, and 65% had not taken antimalarial chemoprophylaxis. Curative quinine treatment was used in 97% of patients. Intensive care unit mortality was 10.5% (42 deaths). By multivariate analysis, three variables at intensive care unit admission were independently associated with hospital death: older age (per 10-year increment, odds ratio [OR], 1.72; 95% confidence interval [95%CI], 1.28-2.32; P = 0.0004), Glasgow Coma Scale score (per 1-point decrease, OR, 1.32; 95%CI, 1.20-1.45; P<0.0001), and higher parasitemia (per 5% increment, OR, 1.41; 95%CI, 1.22-1.62; P<0.0001). In a large population of adults treated in a non-endemic industrialized country, severe malaria still carried a high mortality rate. Our data, including predictors of death, can probably be generalized to other non-endemic countries where high-quality healthcare is available.

Invasive pulmonary aspergillosis (IPA) in intensive care unit patients is a major concern. Influenza-associated acute respiratory distress syndrome (ARDS) and severe COVID-19 patients are both at risk of developing invasive fungal diseases. We used the new international definitions of influenza-associated pulmonary aspergillosis (IAPA) and COVID-19-associated pulmonary aspergillosis (CAPA) to compare the demographic, clinical, biological, and radiological aspects of IAPA and CAPA in a monocentric retrospective study. A total of 120 patients were included, 71 with influenza and 49 with COVID-19-associated ARDS. Among them, 27 fulfilled the newly published criteria of IPA: 17/71 IAPA (23.9%) and 10/49 CAPA (20.4%). Kaplan–Meier curves showed significantly higher 90-day mortality for IPA patients overall (p = 0.032), whereas mortality did not differ between CAPA and IAPA patients. Radiological findings showed differences between IAPA and CAPA, with a higher proportion of features suggestive of IPA during IAPA. Lastly, a wide proportion of IPA patients had low plasma voriconazole concentrations with a higher delay to reach concentrations > 2 mg/L in CAPA vs. IAPA patients (p = 0.045). Severe COVID-19 and influenza patients appeared very similar in terms of prevalence of IPA and outcome. The dramatic consequences on the patients’ prognosis emphasize the need for a better awareness in these particular populations.

Continuous cardiac index (CI) monitoring is frequently used in critically ill patients. Few studies have compared the pulse contour-based device FloTrac/Vigileo ® to pulmonary artery thermodilution (PAC) in terms of accuracy for CI monitoring in septic shock. The aim of our study was to compare the third-generation FloTrac/Vigileo ® to PAC in septic shock. Eighteen patients with septic shock requiring monitoring by PAC were included in this study. We monitored CI using both FloTrac/Vigileo ® and continuous thermodilution (PAC-CI). Hemodynamic data were recorded every hour or every 2 min during fluid challenges. The primary endpoint was the global agreement of all CI-paired measurements determined using the Bland–Altman method adapted to replicated data. We tested the linearity of the bias by regression analysis, and compared the reactivity of the 2 techniques during fluid challenges. A receiver operating characteristic (ROC) curve analysis tested the ability of FloTrac/Vigileo ® to detect concordant and significative CI changes, using PAC-CI as the reference method. Overall, 1,201 paired CI measurements were recorded. The Bland–Altman analysis for global agreement of the 2 techniques showed a bias of −0.1 ± 2.1 L min −1  m −2 and a percentage error of 64 %. The overall correlation coefficient between PAC-CI and FloTrac/Vigileo ® CI was 0.47 ( p  < 0.01), with r 2  = 0.22. The area under the curve of the ROC curve for detecting concordant and significant changes in CI was 0.72 (0.53; 0.87). In our study, third-generation Flowtrac-Vigileo ® appears to be too inaccurate to be recommended for CI monitoring in septic shock.