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SARS-Cov-2 (COVID-19) has become a major worldwide health concern since its appearance in China at the end of 2019.To evaluate the intrinsic mortality and burden of COVID-19 and seasonal influenza pneumonia in ICUs in the city of Lyon, France.A retrospective study.Six ICUs in a single institution in Lyon, France.Consecutive patients admitted to an ICU with SARS-CoV-2 pneumonia from 27 February to 4 April 2020 (COVID-19 group) and seasonal influenza pneumonia from 1 November 2015 to 30 April 2019 (influenza group). A total of 350 patients were included in the COVID-19 group (18 refused to consent) and 325 in the influenza group (one refused to consent). Diagnosis was confirmed by RT-PCR. Follow-up was completed on 1 April 2021.Differences in 90-day adjusted-mortality between the COVID-19 and influenza groups were evaluated using a multivariable Cox proportional hazards model.COVID-19 patients were younger, mostly men and had a higher median BMI, and comorbidities, including immunosuppressive condition or respiratory history were less frequent. In univariate analysis, no significant differences were observed between the two groups regarding in-ICU mortality, 30, 60 and 90-day mortality. After Cox modelling adjusted on age, sex, BMI, cancer, sepsis-related organ failure assessment (SOFA) score, simplified acute physiology score SAPS II score, chronic obstructive pulmonary disease and myocardial infarction, the probability of death associated with COVID-19 was significantly higher in comparison to seasonal influenza [hazard ratio 1.57, 95% CI (1.14 to 2.17); P = 0.006]. The clinical course and morbidity profile of both groups was markedly different; COVID-19 patients had less severe illness at admission (SAPS II score, 37 [28 to 48] vs. 48 [39 to 61], P 0.001 and SOFA score, 4 [2 to 8] vs. 8 [5 to 11], P 0.001), but the disease was more severe considering ICU length of stay, duration of mechanical ventilation, PEEP level and prone positioning requirement.After ICU admission, COVID-19 was associated with an increased risk of death compared with seasonal influenza. Patient characteristics, clinical course and morbidity profile of these diseases is markedly different.

We describe a March 2020 co-occurrence of Legionnaires' disease (LD) and coronavirus disease in France. Severe acute respiratory syndrome coronavirus 2 co-infections were identified in 7 of 49 patients from LD case notifications. Most were elderly men with underlying conditions who had contracted severe pneumonia, illustrating the relevance of co-infection screening.

BACKGROUND For more than 20 years, hip fracture 1-year mortality has remained around 20%. An elevation of the postoperative troponin peak within 72 hours (myocardial injury after noncardiac surgery [MINS]) is associated with a greater risk of short-term mortality in the general population. However, there seem to be conflicting results in the specific population who undergo hip fracture surgery, with some studies finding an association between troponin and mortality and some not. The objective of the present study was to investigate the association of MINS and the short- (before 28th day), intermediate- (before 180th day), and long-term (before 365th day) mortality after hip fracture surgery. METHODS We conducted a single-center retrospective cohort of patients undergoing hip fracture surgery from November 2013 to December 2015. MINS was defined as postoperative troponin peak within the 72 hours >5 ng/L. Four MINS subgroups were defined according to the value of troponin peak (ie, ≥5

OBJECTIVES: Little is known about the epidemiology of ventilator-acquired pneumonia among coronavirus disease 2019 patients such as incidence or etiological agents. Some studies suggest a higher risk of ventilator-associated pneumonia in this specific population. DESIGN: Cohort exposed/nonexposed study among the REA-REZO surveillance network. SETTING: Multicentric; ICUs in France. PATIENTS: The coronavirus disease 2019 patients at admission were matched on the age, sex, center of inclusion, presence of antimicrobial therapy at admission, patient provenance, time from ICU admission to mechanical ventilation, and Simplified Acute Physiology Score II at admission to the patients included between 2016 and 2019 within the same surveillance network (1:1). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The overall incidence of ventilator-associated pneumonia, the cumulative incidence, and hazard rate of the first and the second ventilator-associated pneumonia were estimated. In addition, the ventilator-associated pneumonia microbiological ecology and specific resistant pattern in coronavirus disease 2019 exposed and nonexposed patients were compared. Medication data were not collected. A total of 1,879 patients were included in each group. The overall incidence of ventilator-associated pneumonia was higher among coronavirus disease 2019 exposed patients (25.5; 95% CI [23.7-27.45] vs 15.4; 95% CI [13.7-17.3] ventilator-associated pneumonia per 1,000 ventilation days). The cumulative incidence was higher for the first and the second ventilator-associated pneumonia among the coronavirus disease 2019 exposed patients (respective Gray test p < 0.0001 and 0.0167). The microbiological ecology and resistance were comparable between groups with a predominance of Enterobacterales and nonfermenting Gram-negative bacteria. The documented resistance pattern was similar between groups, except for a lower rate of methicillin-resistant Staphylococcus aureus in the coronavirus disease 2019 exposed patient (6% vs 23%; p = 0.013). CONCLUSIONS: There was a higher incidence of ventilator-associated pneumonia occurring among coronavirus disease 2019 patient compared with the general ICU population, with a similar microbiological ecology and resistance pattern.

Increased preoperative delay in patients with hip fractures may be responsible for increased morbidity and mortality. We hypothesized that a strategy of reversal of vitamin K antagonist (VKA) by prothrombin complexes concentrates (PCCs), as compared to vitamin K, is safe and reduces preoperative delay and hospital length of stay (LOS).In this pilot study, we reviewed the records of patients admitted to a university-affiliated hospital for hip fracture between Jan. 1, 2012, and Dec. 31, 2016, who were taking VKA. Patients were stratified according to reversal strategy (vitamin K v. PCC). Adverse effects, time to surgery, LOS and mortality were collected from the electronic medical record and were compared between the 2 study groups and a control group not treated with VKA.A total of 141 patients were included in the study: 65 in the vitamin K group, 26 in the PCC group and 50 in the control group. The median preoperative delay in the PCC group (20 h [interquartile range (IQR)] 13-25 h]) and the control group (20 h [IQR 15-33 h]) was lower than that in the vitamin K group (45 h [IQR 31-52 h]) (p0.001). Patients in the PCC group had a shorter median hospital LOS than those in the vitamin K group (6 d [IQR 4-9 d] v. 8 d [IQR 6-11 d], p0.05). No difference was observed in the proportion of patients who received a red blood cell transfusion, or had thrombotic or hemorrhagic complications. No difference in mortality at 12 months was observed between the groups.In patients with hip fracture, the use of PCCs as compared to vitamin K to reverse the effect of VKA significantly reduced preoperative delay and hospital LOS, and was not associated with an increase in the rates of thrombotic or hemorrhagic complications. Prospective studies involving a greater number of patients are required to confirm these promising results.L’allongement du délai préopératoire chez les patients atteints d’une fracture de la hanche pourrait expliquer l’augmentation de la morbidité et de la mortalité. Selon notre hypothèse, une stratégie d’inversion des antagonistes de la vitamine K (AVK) au moyen de concentrés de complexes prothrombiques (CCP), plutôt que de vitamine K, est sécuritaire et réduit le délai préopératoire et la durée du séjour hospitalier.Pendant cette étude pilote, nous avons passé en revue les dossiers de patients sous AVK admis dans un centre universitaire pour fracture de la hanche entre le 1er janvier 2012 et le 31 décembre 2016. Les patients ont été stratifiés selon la stratégie d’inversion choisie (vitamine K c. CCP). Les effets indésirables, le délai préopératoire, la durée du séjour hospitalier et la mortalité ont été recueillis à partir des dossiers médicaux électroniques et ont été comparés entre les 2 groupes de l’étude et un groupe témoin non sous AVK.En tout, 141 patients ont été inclus dans l’étude, 65 dans le groupe sous vitamine K, 26 dans le groupe sous CCP et 50 dans le groupe témoin. Le délai préopératoire médian pour le groupe sous CCP (20 h [éventail interquartile (ÉIQ)] 13–25 h]) et le groupe témoin (20 h [ÉIQ 15–33 h]) a été plus bref que pour le groupe sous vitamine K (45 h [ÉIQ 31–52 h]) (p0,001). Les patients du groupe sous CCP ont eu un séjour hospitalier médian plus bref que les patients du groupe sous vitamine K (6 j [ÉIQ 4–9 j] c. 8 j [ÉIQ 6–11 j]) (p0,05). Aucune différence n'a été observée quant à la proportion de patients ayant reçu une transfusion de culot globulaire ou ayant manifesté des complications thrombotiques ou hémorragiques. Aucune différence quant à la mortalité à 12 mois n'a été observée entre les groupes.Chez les patients atteints d’une fracture de la hanche, l’utilisation des CCP plutôt que de la vitamine K pour inverser l’effet des AVK a significativement abrégé le délai préopératoire et la durée du séjour hospitalier, et n’a pas été associée à une augmentation des taux de complications thrombotiques ou hémorragiques. Des études prospectives sur un plus grand nombre de patients sont nécessaires pour confirmer ces résultats prometteurs.

BACKGROUND: The prevalence of current electronic cigarette (e-cigarette) use has increased dramatically among US youth. It is unknown how the impact of policies to curb e-cigarette use might differ across rural and urban areas. METHODS: Data were collected from an annual statewide survey of middle and high school students in Kansas. Multivariable logistic regression was performed to examine the temporal change in current e-cigarette use in 2018 and 2019 across rural and urban areas and across the areas with and without a Tobacco 21 (T21) policy that raises the minimum age of tobacco sales to 21 years. RESULTS: Of 132 803 participants, the prevalence of current e-cigarette use increased from 8.2% in 2018 to 12.6% in 2019. The increase was larger in rural areas (from 6.7% in 2018 to 13.4% in 2019, difference = 6.7%) than in urban areas (9.8%–11.9%, difference = 2.1%), with a significant interaction effect of year × urbanicity/T21 group (P < .0001). In urban areas, e-cigarette use increased significantly for middle school students in T21 areas (3.3%–4.5%; P = .01) and all students in non-T21 areas (8.1%–12.0%; P < .0001). In rural areas, the increase in e-cigarette use was significant in both T21 and non-T21 areas for all students, but the increase was smaller in T21 (7.9%–10.8%, difference = 3.0%) than in non-T21 areas (6.5%–13.7%, difference = 7.1%). CONCLUSIONS: In this study, we reported marked disparities in the increase of youth e-cigarette use, with a larger recent increase in rural than in urban areas. T21 policies appear to mitigate these increases in both rural and urban youth.

Data on the relationship between antimicrobial resistance and mortality remain scarce, and this relationship needs to be investigated in intensive care units (ICUs). The aim of this study was to compare the ICU mortality rates between patients with ICU-acquired pneumonia due to highly antimicrobial-resistant (HAMR) bacteria and those with ICU-acquired pneumonia due to non-HAMR bacteria. We conducted a multicenter, retrospective cohort study using the French National Surveillance Network for Healthcare Associated Infection in ICUs (“REA-Raisin”) database, gathering data from 200 ICUs from January 2007 to December 2016. We assessed all adult patients who were hospitalized for at least 48 h and presented with ICU-acquired pneumonia caused by S. aureus, Enterobacteriaceae, P. aeruginosa, or A. baumannii. The association between pneumonia caused by HAMR bacteria and ICU mortality was analyzed using the whole sample and using a 1:2 matched sample. Among the 18,497 patients with at least one documented case of ICU-acquired pneumonia caused by S. aureus, Enterobacteriaceae, P. aeruginosa, or A. baumannii, 3081 (16.4%) had HAMR bacteria. The HAMR group was associated with increased ICU mortality (40.3% vs. 30%, odds ratio (OR) 95%, CI 1.57 [1.45–1.70], P P P

OBJECTIVE: The authors report on a case of a 59-year-old man hospitalized in the intensive care unit because of severe SARS-COV-2 infection (COVID-19). BACKGROUND: The patient had several comorbidities, including liver cirrhosis. He developed ventilation-associated bacterial pneumonia for which he was administered cefepime at an initial dose of 2 g/8 hours. Therapeutic drug monitoring was performed, showing overexposure with an initial trough concentration of >60 mg/L. METHODS: Analysis of pharmacokinetic data and model-based dose adjustment was performed using BestDose software. RESULTS: The patient had unexpected pharmacokinetic parameter values. Serum creatinine was only moderately increased, whereas measured creatinine clearance based on urine collection showed impaired renal function. Bacterial minimum inhibitory concentration was also considered in the dosing decisions. After dose reduction to 0.5 g/8 hours, the cefepime trough concentration progressively declined and reached the target values by the end of the therapy. A post-hoc analysis provided a different interpretation of drug overexposure. CONCLUSION: This case report illustrates how physiological, microbiological, and drug concentration data can be used for model-based dosage individualization of cefepime in intensive care unit patients.

Background Raising the minimum legal age (MLA) of tobacco sales from 18 to 21 (Tobacco 21 [T21]) has recently been implemented nationwide as a method to reduce tobacco use, but empirical data on youth knowledge of T21 policies and related pathways to tobacco use are limited. Methods Data were collected from the 2018 Kansas Communities That Care Student Survey. Knowledge of the MLA was compared between T21 and non-T21 regions using a quasi-experimental design. Logistic regression and mediation analysis were conducted to assess the association between knowledge of the MLA, influencing factors, and intention to use tobacco. Results Of 16 949 students (aged between 11 and 18) completing the T21 survey, fewer students responded correctly about the MLA in T21 than in non-T21 regions (37.4% vs. 46.3% responded correctly, 27.6% vs. 24.2% responded incorrectly, respectively). In T21 regions, Hispanics and students who support T21 were more likely to respond correctly about the MLA. Among current non-tobacco users in T21 regions, students who responded correctly about the MLA were less likely to report intention to use tobacco (adjusted odds ratio [AOR] = 0.7, 95% confidence interval [CI]: [0.6–0.8]) than those who responded incorrectly. The pathway from knowledge of the MLA to intention to use tobacco was significantly mediated by increased support for T21 (p = .002), perceived difficulty in accessing cigarettes (p = .042), and reduced susceptibility to peer influence (p = .027). Conclusions Knowledge of the MLA was inversely associated with intention to use tobacco among youth. Educational campaigns to raise awareness and support for T21 among youth may improve the impact of T21 policies. Implications This study examined youth knowledge of the MLA to purchase tobacco products, and whether knowledge of the MLA was associated with reduced intention to use tobacco. It also examined other influencing factors (eg, perceived support for T21) and potential mediation pathways linking knowledge of the MLA with intention to use tobacco. Given the nationwide adoption of T21, educational campaigns to promote knowledge of the policy may improve its impact.

Background: Candidemia is a major cause of mortality in the intensive care unit (ICU). According to the Infectious Diseases Society of America (IDSA), an echinocandin is recommended as initial therapy and fluconazole as an alternative. In a context of echinocandin resistance development, the question arising is whether azoles are a suitable alternative to echinocandins for the treatment of candidemia in critically ill patients. Methods: A 3-year (2015–2017) retrospective multicentric cohort study was conducted. Adult patients with a diagnosis of candidemia during the ICU stay and treated with echinocandins or azoles were included. Demographic, clinical data, mycological data, and antifungal treatments were collected. Kaplan–Meier survival analysis, univariate analysis, and a multivariate logistic regression analysis using a propensity score with the inverse probability of treatment weighting method were performed. Findings: Seventy-nine patients (n = 79) were analyzed. Treatment success, as well as survival on day 90 (Kaplan–Meier survival analysis, log rank test, p = 0.542), were comparable between patients who received echinocandins (caspofungin (n = 47)) or azoles (fluconazole (n = 29) or voriconazole (n = 3)). A multivariable analysis demonstrated that higher SOFA score on the day of candidemia diagnosis and absence of adequate Candida source control were independently associated with a greater risk of 90-day mortality, whereas azoles treatment was not associated with an excess 90-day mortality. Interpretation: This study confirms that the use of azoles recommended for candidemia, mostly fluconazole, as a first-line therapy is a reasonable alternative to caspofungin for ICU patients in our institution. This needs to be included in local guidelines through antifungal stewardship programs. Keywords: Candidemia, Caspofungin, Fluconazole, Voriconazole, Mortality, Propensity score

© 2020 Elsevier Ltd Background: Observational studies have suggested that accelerated surgery is associated with improved outcomes in patients with a hip fracture. The HIP ATTACK trial assessed whether accelerated surgery could reduce mortality and major complications. Methods: HIP ATTACK was an international, randomised, controlled trial done at 69 hospitals in 17 countries. Patients with a hip fracture that required surgery and were aged 45 years or older were eligible. Research personnel randomly assigned patients (1:1) through a central computerised randomisation system using randomly varying block sizes to either accelerated surgery (goal of surgery within 6 h of diagnosis) or standard care. The coprimary outcomes were mortality and a composite of major complications (ie, mortality and non-fatal myocardial infarction, stroke, venous thromboembolism, sepsis, pneumonia, life-threatening bleeding, and major bleeding) at 90 days after randomisation. Patients, health-care providers, and study staff were aware of treatment assignment, but outcome adjudicators were masked to treatment allocation. Patients were analysed according to the intention-to-treat principle. This study is registered at ClinicalTrials.gov (NCT02027896). Findings: Between March 14, 2014, and May 24, 2019, 27 701 patients were screened, of whom 7780 were eligible. 2970 of these were enrolled and randomly assigned to receive accelerated surgery (n=1487) or standard care (n=1483). The median time from hip fracture diagnosis to surgery was 6 h (IQR 4–9) in the accelerated-surgery group and 24 h (10–42) in the standard-care group (p

Amikacin is commonly used for probabilistic antimicrobial therapy in critically ill patients with sepsis. Its narrow therapeutic margin makes it challenging to determine the right individual dose that ensures the highest efficacy target attainment rate (TAR) in this setting. This study aims to develop a new initial dosing approach for amikacin by optimizing the a priori TAR in this population. A population pharmacokinetic model was built with a learning data set from critically ill patients who received amikacin. It was then used to design an initial dosing approach maximizing a priori TAR for a target ratio of ≥8 for the peak concentration to the MIC (C(max)/MIC) or of ≥75 for the ratio of the area under the concentration-time curve from 0 to 24 h to the MIC (AUC(0–24)/MIC). In the 166 patients included, 53% had amikacin C(max) of ≥64 mg/liter with a median dose of 23.4 mg/kg. A two-compartment model with creatinine clearance and body surface area as covariates best described the data and showed good predictive performance. Our dosing approach was successful in optimizing TAR for C(max)/MIC, with a rate of 92.9% versus 67.9% using a 30-mg/kg regimen, based on an external subset of data and assuming a MIC of 8 mg/liter. Mean optimal doses were higher (3.5 ± 0.5 g) than with the 30-mg/kg regimen (2.1 ± 0.3 g). Suggested doses varied with the MIC, the target index, and desired TAR threshold. A dosing algorithm based on the method is proposed for a large range of patient covariates. Clinical studies are necessary to confirm efficacy and safety of this optimized dosing approach.

Purpose Several remarks have been raised regarding the variables and cut-points used in the Sequential Organ Failure Assessment (SOFA) score. This study revisited the SOFA score and created a new simplified and accurate sa-SOFA score. Methods The study grouped four prospective cohorts (2005–2016) of patients with Systemic Inflammatory Response Syndrome. It collected 28-day mortality, sociodemographic characteristics, and the SOFA score with all variable values at Day 1. A logistic regression analysis was used to select the most relevant variables and a minimum p value approach with a 10-fold cross-validation were used to find the optimal partition of selected variables. The minimum number of cut-points (2, 3, or 4) was also tested by comparing the distributions of areas under receiver operating characteristic (AUROC) curves. Results Among the 1436 participants, 416 died within 28 days (28.9%). The sa-SOFA kept one variable per dimension and two cut-points per variable. The AUROC curves that investigated the abilities of the sa-SOFA and SOFA scores to predict 28-day mortality were 0.739 [0.712–0.768] and 0.687 [0.656–0.717], respectively (p-value of DeLong test Conclusion Keeping the conventional SOFA dimension variables, the new sa-SOFA proved to be simpler and more accurate in predicting 28-day mortality.

International audience; Amikacin antimicrobial effect has been correlated with the ratio of the peak concentration (Cmax ) to the minimum inhibitory concentration. A target Cmax >= 60-80 mg/L has been suggested. It has been shown that such target is not achieved in a large proportion of critically ill patients in intensive care units. A retrospective analysis was performed to examine the determinants of Cmax >= 80 mg/L on the first peak in 339 critically ill patients treated by amikacin. The influence of available variables on Cmax target attainment was analyzed using a classification and regression tree (CART) and logistic regression. Mean Cmax in the 339 patients was 73.0 \textpm 23.9 mg/L, with a target attainment rate (TAR, Cmax >= 80 mg/L) of 37.5%. In CART analysis, the strongest predictor of amikacin target peak attainment was dose per kilogram of lean body weight (dose/LBW). TAR was 60.1% in patients with dose/LBW >= 37.8 vs. 19.9% in patients with lower dose/LBW (OR = 6.0 (95% CI: 3.6-10.2)). Renal function was a secondary predictor of Cmax . Logistic regression analysis identified dose per kilogram of ideal body weight (OR = 1.13 (95% CI: 1.09-1.17)) and creatinine clearance (OR = 0.993 (95% CI: 0.988-0.998)) as predictors of target peak achievement. Based on our results, an amikacin dose >= 37.8 mg/kg of LBW should be used to optimize the attainment of Cmax >= 80 mg/L after the first dose in critically ill patients. An even higher dose may be necessary in patients with normal renal function.

Severe septic syndromes deeply impair innate and adaptive immunity and are responsible for sepsis-induced immunosuppression. Although neutrophils represent the first line of defense against infection, little is known about their phenotype and functions a few days after sepsis, when the immunosuppressive phase is maximal (i.e., between d 3 and 8). The objective of the present study was to perform, for the first time, a global evaluation of neutrophil alterations in immunosuppressed septic patients (at d 3–4 and d 6–8) using phenotypic and functional studies. In addition, the potential association of these parameters and deleterious outcomes was assessed. Peripheral blood was collected from 43 septic shock patients and compared with that of 23 healthy controls. In the septic patients, our results highlight a markedly altered neutrophil chemotaxis (functional and chemokine receptor expressions), oxidative burst, and lactoferrin content and an increased number of circulating immature granulocytes (i.e., CD10dimCD16dim). These aspects were associated with an increased risk of death after septic shock. In contrast, phagocytosis and activation capacities were conserved. To conclude, circulating neutrophils present with phenotypic, functional, and morphologic alterations a few days after sepsis onset. These dysfunctions might participate in the deleterious role of sepsis-induced immunosuppression. The present results open new perspectives in the mechanisms favoring nosocomial infections after septic shock. They deserve to be further investigated in a larger clinical study and in animal models recapitulating these alterations.

OBJECTIVE Quick identification of septic source is fundamental in patients with severe sepsis of unknown origin. The purpose of this case report was to assess the benefit and feasibility of an early PET-CT in critically ill patients with undiagnosed sepsis. DATA SOURCES Clinical observations of two patients. STUDY SELECTION Case reports. DATA EXTRACTION Data extracted from medical records, after patient's consent. Illustrations were collected from the imaging software. DATA SYNTHESIS We admitted two critically ill patients for suspected sepsis and altered mental state. As all bacteriological samples were initially sterile, diagnostic workups in both patients led us to suspect underlying malignant hemopathy. In fact, the lumbar puncture of the first patient revealed a large B-cell lymphoma, and an acquired thrombotic thrombocytopenic purpura was suspected in the second patient. However, PET-CTs performed in both patients displayed infra-clinical underlying infectious foci. Within 48 hours, both patients developed a clearly identified sepsis linked to the described focus, and favorable outcome thanks to the precious information delivered by the PET-CT. CONCLUSIONS PET-CT precisely detected the deep foci of infection about 48 hours prior to the diagnosis of sepsis. The cases reports suggested the use of this image technique in ICU for patients with sepsis of unknown origin.

Purpose Intensive care unit (ICU)-acquired infections (IAI) result in increased hospital and ICU stay, costs and mortality. To date, no biomarker has shown sufficient evidence and ease of application in clinical routine for the identification of patients at risk of IAI. We evaluated the association of the systemic mRNA expression of two host response biomarkers, CD74 and IL10, with IAI occurrence in a large cohort of ICU patients. Methods ICU patients were prospectively enrolled in a multicenter cohort study. Whole blood was collected on the day of admission (D1) and on day 3 (D3) and day 6 (D6) after admission. Patients were screened daily for IAI occurrence and data were censored after IAI diagnosis. mRNA expression levels of biomarkers were measured using RT-qPCR. Fine and Gray competing risk models were used to assess the association between gene expression and IAI occurrence. Results A total of 725 patients were analyzed. At least one IAI episode occurred in 137 patients (19%). After adjustment for shock and sepsis status at admission, CD74 and IL10 levels were found to be significantly associated with IAI occurrence [subdistribution hazard ratio (95% confidence interval) 0.67 (0.46–0.97) for CD74 D3/D1 expression ratio and 2.21 (1.63–3.00) for IL10 at D3]. IAI cumulative incidence was significantly different between groups stratified according to CD74 or IL10 expression (Gray tests p

A new pathway of three protein tyrosine kinase receptors, namely, the TAM receptor family [Tyro-3, Axl and Mer tyrosine kinase (MerTK)], has recently been described to negatively control immune responses. The objective of this prospective, observational, clinical study was to investigate the expression patterns of TAM receptors in circulating white blood cells collected from patients with septic shock.The expression of TAM receptors was measured by flow cytometry in circulating leukocytes from patients with septic shock sampled on days (D) 1-2 (n = 47) and D3-4 (n = 37) after the onset of shock, severe trauma patients at D1-2 after trauma (n = 51) and healthy individuals (n = 23).On D1-2 after injury, MerTK was overexpressed in monocytes and neutrophils collected from patients with septic shock in comparison with those collected from healthy volunteers and trauma patients. This phenomenon was also observed for mRNA. Conversely, the expression of Tyro-3 and Axl was higher in monocytes from trauma patients versus healthy volunteers or those in septic shock. MerTK expression between D1-2 and D3-4 remained elevated in patients suffering from septic shock who died or developed an intensive care unit-acquired infection, whereas it decreased in patients who recovered uneventfully. This in vivo observed expression pattern was reproduced ex vivo after the incubation of healthy volunteer cells with plasma from septic shock or trauma patients.MerTK expression in circulating innate immune cells is increased in patients with septic shock in comparison with healthy volunteers and trauma patients. Persistent MerTK overexpression after septic shock is associated with adverse outcome. The role of this family of receptors in the pathophysiology of injury-induced immune dysfunctions deserves to be specifically investigated.

Septic patients develop immune dysfunctions, the intensities and durations of which are associated with deleterious outcomes. LILRB2 (leukocyte immunoglobulin-like receptors subfamily B, member 2), an inhibitory member of the LILR family of receptors, is known for its immunoregulatory properties. In a microarray study, we identified LILRB2 as an upregulated gene in septic shock patients. On monocytes primed with LPS ex vivo, LILRB2 mRNA and protein expressions were dose-dependently downregulated and subsequently highly upregulated versus non-stimulated cells. This is concordant with clinical data, since both LILRB2 mRNA and protein expressions were significantly increased in septic shock patients at day 3. In a cohort of more than 700 patients, only after septic shock were LILRB2 mRNA levels increased compared with non-infected or less severely infected patients. This was preceded by a phase of downregulated mRNA expression during the first hours after septic shock. Interestingly, the intensity of this decrease was associated with increased risk of death after septic shock. LILRB2 protein and mRNA expressions are deregulated on monocytes after septic shock and this can be reproduced ex vivo after LPS challenge. Considering LILRB2 inhibitory properties, we can hypothesize that LILRB2 may participate in the altered immune response after septic shock.

Background Chemokine (C-X3-C motif) receptor 1 (CX3CR1) was identified as the most differentially expressed gene between survivors and non-survivors in two independent cohorts of septic shock patients and was proposed as a marker of sepsis-induced immunosuppression. Whether such a biomarker is associated with mortality in the heterogeneous group of critically ill patients is unknown. The primary objective of this study was to evaluate the association between CX3CR1 messenger RNA (mRNA) expression and mortality in intensive care unit (ICU) patients. The secondary objective was to evaluate similar endpoints in the subgroup of septic shock patients. Methods We performed a prospective, multicentre, non-interventional study in six ICUs of university hospitals in Lyon, France. Every consecutive adult patient with systemic inflammatory response syndrome and an expected length of stay in the ICU over 2 days was included. Whole-blood CX3CR1 mRNA expression was measured by quantitative real-time polymerase chain reaction at day 1 (D1) and D3 after inclusion. Results In ICU patients (n = 725), decreased CX3CR1 mRNA expression at D1 was associated with high D7 mortality (AUC 0.70, adjusted OR [aOR] 2.03, 95 % CI 1.19–3.46), while decreased expression at D3 was associated with increased D28 mortality (AUC 0.64, aOR 2.34, 95 % CI 1.45–3.77). In septic shock patients (n = 279), similar associations were observed between decreased D1 CX3CR1 mRNA expression and D7 mortality (AUC 0.69, aOR 2.76, 95 % CI 1.32–5.75) as well as decreased D3 expression and D28 mortality (AUC 0.72, aOR 3.98, 95 % CI 1.72–9.23). These associations were independent of lactacidaemia, Simplified Acute Physiology Score II, Sepsis-related Organ Failure Assessment score and Charlson comorbidity index. Conclusions This study represents the largest evaluation of such an mRNA marker in a heterogeneous cohort of severely injured patients. Our results show that decreased CX3CR1 mRNA expression is associated with increased mortality in ICU patients. This suggests a link between injury-induced immunosuppression and mortality in critically ill patients. In this context, the monitoring of such a host response molecular biomarker could prove very helpful for the identification of patients at high risk of death in the ICU. Electronic supplementary material The online version of this article (doi:10.1186/s13054-016-1362-x) contains supplementary material, which is available to authorized users.

Sepsis represents the host's systemic inflammatory response to an infection. In this condition, immune response associates a marked inflammatory response and the delayed development of severe dysfunctions affecting both innate and adaptive responses. As neutrophils are the first line of defense against infection, they are central to the pathophysiology of sepsis in first hours. Nevertheless, their role during immunosuppression phase remains elusive. The main objective of the current work was to perform a transcriptomic study on purified neutrophils from septic shock patients (n=9) so as to identify genes that are differentially expressed during the first week after disease onset both (3-4 and 6-8days) versus healthy donors. Then, 45 septic shock patients were prospectively enrolled to confirm results at the protein level using flow cytometry. Twenty healthy volunteers (HV) were also included for the whole study. By comparing the transcriptome of purified neutrophils, we identified 364 up-regulated and 328 down-regulated genes differentially expressed. Of them, CD177 mRNA, coding for an activation molecule in chemotaxis, had the highest fold change modulation between patients and HV. This increase was then confirmed at the protein level. There was a constant subset of neutrophils that did not express CD177. However, when positive, septic neutrophils presented with significantly increased CD177 expression. Of note, no association between CD177 overexpression and features of immunosuppression has been highlighted. In addition, this up-regulation was negatively correlated with a decreased expression of CD10, a characteristic of immature myeloid cells. In conclusion, in this exploratory work, we shed light on the increased CD177 mRNA and protein expressions in circulating neutrophils after septic shock. Considering the potential dual roles of CD177 neutrophil (i.e., maturation/chemotaxis), negatively correlated in this study, its participation in septic shock pathophysiology deserves further investigation. Furthermore, its potential as a biomarker for sepsis would deserve to be investigated in large cohorts of patients.

International audience; OBJECTIVES:Low first-dose peak serum concentrations of amikacin and gentamicin are commonly reported in ICU patients. The present study aimed to assess whether 30 mg/kg amikacin or 8 mg/kg gentamicin achieved target concentrations in ICU patients with severe sepsis.PATIENTS AND METHODS:Sixty-three ICU patients (Simplified Acute Physiology Score II = 43 ± 16) with severe sepsis and an indication for intravenous amikacin (n = 47) or gentamicin (n = 16) were included. The first (30 mg/kg amikacin; 8 mg/kg gentamicin) and subsequent doses and corresponding peak concentrations (30 min after the completion of an infusion) were recorded. French guideline target concentrations were ≥60 and ≥30 mg/L for amikacin and gentamicin, respectively. A target pharmacokinetic/pharmacodynamic ratio of 10 × MIC was also measured.RESULTS:Pulmonary, abdominal and urinary tract infections were diagnosed in 56 patients. Infection was confirmed in 37 patients (59%). The targeted first-dose peak concentration was achieved in 37/63 patients (59%) [amikacin 36/47 (77%) and gentamicin 1/16 (6%)], and 59/63 patients (94%) achieved the pharmacokinetic/pharmacodynamic ratio using the MIC data that were available from 21 patients. However, the second dose of aminoglycoside was withheld because of high trough concentrations in nearly half of patients who did not have renal dysfunction.CONCLUSIONS:In this study, 30 mg/kg amikacin and 8 mg/kg gentamicin led to target peak serum concentrations in 59% of patients.

Background and objectives For patients suffering from peritoneal carcinomatosis, cytoreductive surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) is the only curative option. We focused on severe complications in the postoperative course of HIPEC. Methods We studied perioperative data from patients who underwent HIPEC between January 2010 and August 2011. Our primary objective was to identify perioperative risk factors for ICU admission. Our secondary objective was to identify patient that may be re-admitted to the ICU thanks to a prognostic score. Results 122 patients underwent HIPEC. 32 presented severe adverse events (26.2%) and 7 died (5.7%). Reasons for ICU admission were septic shock in 28.1% of patients, hemorrhagic shock for 21.9%, hemodynamic instability for 15.6%, respiratory causes for 6.2% and post-operative acidosis for 6.2%. Vasopressors were required for 34% and 40.6% were mechanically ventilated. Conclusion Peritoneal cancer index, diaphragmatic peritonectomy, the need of vasopressive therapy, total volume of fluid leakage collected in drains and total volume of fluid therapy administered at day 1 reported on ideal body weight were the 5 significant variables that we combined to build a morbidity prognostic score. One patient over 4 is likely to present severe complications. A predictive morbidity score provide informative data for clinicians.

The uptake and clearance of apoptotic cells by macrophages and other phagocytic cells, a process called efferocytosis, is a major component in the resolution of inflammation. Increased concentrations of extracellular histones are found during acute inflammatory states and appear to contribute to organ system dysfunction and mortality. In these studies, we examined the potential role of histones in modulating efferocytosis. We found that phagocytosis of apoptotic neutrophils or thymocytes by macrophages was significantly diminished in the presence of histones H3 or H4, but not histone H1. Histone H3 demonstrated direct binding to macrophages, an effect that was diminished by preincubation of macrophages with the opsonins growth arrest-specific gene 6 (Gas6) and milk fat globule-epidermal growth factor (EGF) 8 (MFG-E8). Incubation of histone H3 with soluble α(v)β₅ integrin and Mer, but not with α(v)β₃, diminished its binding to macrophages. Phagocytosis of apoptotic cells by alveolar macrophages in vivo was diminished in the presence of histone H3. Incubation of histone H3 with activated protein C, a treatment that degrades histones, abrogated its inhibitory effects on efferocytosis under both in vitro and in vivo conditions. The present studies demonstrate that histones have inhibitory effects on efferocytosis, suggesting a new mechanism by which extracellular histones contribute to acute inflammatory processes and tissue injury.

Phagocytosis of apoptotic cells by macrophages, known as efferocytosis, is a critical process in the resolution of inflammation. High mobility group box 1 (HMGB1) protein was first described as a nuclear nonhistone DNA-binding protein, but is now known to be secreted by activated cells during inflammatory processes, where it participates in diminishing efferocytosis. Although HMGB1 is known to undergo modification when secreted, the effect of such modifications on the inhibitory actions of HMGB1 during efferocytosis have not been reported. In the present studies, we found that HMGB1 secreted by Toll-like receptor 4 (TLR4) stimulated cells is highly poly(ADP-ribosyl)ated (PARylated). Gene deletion of poly(ADP)-ribose polymerase (PARP)-1 or pharmacological inhibition of PARP-1 decreased the release of HMGB1 from the nucleus to the extracellular milieu after TLR4 engagement. Preincubation of macrophages or apoptotic cells with HMGB1 diminished efferocytosis through mechanisms involving binding of HMGB1 to phosphatidylserine on apoptotic cells and to the receptor for advanced glycation end products (RAGE) on macrophages. Preincubation of either macrophages or apoptotic cells with PARylated HMGB1 inhibited efferocytosis to a greater degree than exposure to unmodified HMGB1, and PARylated HMGB1 demonstrated higher affinity for phosphatidylserine and RAGE than unmodified HMGB1. PARylated HMGB1 had a greater inhibitory effect on Ras-related C3 botulinum toxin substrate 1 (Rac-1) activation in macrophages during the uptake of apoptotic cells than unmodified HMGB1. The present results, showing that PARylation of HMGB1 enhances its ability to inhibit efferocytosis, provide a novel mechanism by which PARP-1 may promote inflammation.

High mobility group box 1 (HMGB1) is a highly conserved protein with multiple intracellular and extracellular functions, including transcriptional regulation, as well as modulation of inflammation, cell migration, and ingestion of apoptotic cells. In these experiments, we examined a potential role for intracellular HMGB1 in modulating phagocytosis. We found that phagocytosis of apoptotic cells resulted in translocation of HMGB1 into the cytoplasm and extracellular space. Transient or stable inhibition of HMGB1 expression in bone marrow-derived macrophages or fibroblasts resulted in increased phagocytosis of apoptotic thymocytes and apoptotic neutrophils. Knockdown of HMGB1 was associated with enhanced activation of Rac-1 and cytoskeletal rearrangement. Intracellular events involved in phagocytosis and upstream of Rac-1 activation, such as phosphorylation of ERK and focal adhesion kinase (FAK), were increased after knockdown of HMGB1. Inhibition of Src kinase activity prevented the increase in phosphorylation of FAK and ERK present during phagocytosis in HMGB1 knockdown cells, and also abrogated the enhancement in phagocytosis associated with HMGB1 knockdown. Interaction between Src and FAK in the cytoplasm of HMGB1 knockdown fibroblasts was enhanced compared with that present in control fibroblasts. Under in vitro conditions, the presence of HMGB1 diminished interactions between purified FAK and Src. These studies demonstrate a novel role for HMGB1 in the regulation of phagocytosis. In particular, these experiments show that intracellular HMGB1, through associating with Src kinase and inhibiting interactions between Src and FAK, diminishes the phagocytic ability of macrophages and other cell populations.

Enterococci may increase morbidity and mortality in elderly patients with intra-abdominal infections (IAIs) hospitalized in the intensive care unit (ICU).A single-centre, retrospective evaluation of an ICU database (1997-2007) of elderly ICU patients (≥75 years) with a severe IAI was performed. Demographics, severity scores, underlying diseases, microbiology and outcomes were recorded. Patients with enterococci isolated in peritoneal fluid (E+ group) were compared with those lacking enterococci in peritoneal fluid (E- group). Stepwise multivariate logistic regression was used to identify independent factors associated with mortality.One hundred and sixty patients were included (mean ± SD age 82 ± 5 years; n = 72 in the E+ group). The E+ group was more severely ill than the E- group, with higher Simplified Acute Physiologic Score 2 (61 ± 20 versus 48 ± 16, P = 0.0001) and Sequential Organ Failure Assessment scores (8 ± 3 versus 5 ± 3, P = 0.0001), a greater postoperative infection rate (58.3% versus 34.1%, P = 0.01), a higher incidence of inappropriate empirical antimicrobial therapies (33.3% versus 19.3%, P = 0.04), a longer duration of mechanical ventilation (11.8 ± 10.9 versus 7.8 ± 10.2 days, P = 0.02) and greater vasopressor use (7.2 ± 7.1 versus 3.3 ± 4.1 days, P = 0.001). ICU mortality was higher in the E+ group than in the E- group (54.2% versus 38.6%, P = 0.05). In the multivariate analysis, E+ status was independently associated with mortality (odds ratio 2.24; 95% confidence interval 1.06-4.75; P = 0.03).In severely ill, elderly patients in the ICU for an IAI, the isolation of enterococci was associated with increased disease severity and morbidity and was an independent risk factor for mortality.

Phagocytosis of apoptotic cells is critical to resolution of inflammation. High mobility group box 1 protein (HMGB1), a mediator of inflammation, has been shown to diminish phagocytosis through binding to phosphatidylserine (PS) exposed on the surface of apoptotic neutrophils. However, it is currently unknown whether HMGB1 also modulates the activity of receptors involved in PS recognition on the surface of phagocytes. In the present studies, we found that preincubation of macrophages with HMGB1 decreased their ability to engulf apoptotic neutrophils or thymocytes. Preincubation of macrophages with HMGB1 prevented the enhancement of efferocytosis resulting from exposure to milk fat globule EGF factor 8 (MFG-E8), an opsonin that bridges PS and αvβ3 as well as αvβ5-integrins on the surface of phagocytes. The inhibitory effect of HMGB1 on the phagocytic activity of macrophages was prevented by preincubation of HMGB1 with soluble αvβ3, but not with soluble αvβ5. HMGB1 colocalized with the β3-integrin on the cell membrane of macrophages and bound to soluble αvβ3, but not to soluble αvβ5. HMGB1 suppressed the interaction between MFG-E8 and αvβ3. HMGB1 also inhibited intracellular signaling events, including ERK phosphorylation and Rac-1 activation, which are activated in macrophages during phagocytosis of apoptotic cells. These results demonstrate that HMGB1 blocks αvβ3-dependent recognition and uptake of apoptotic cells.

The HMGB1 C-terminal tail is responsible for the in vitro and in vivo inhibitory effects of HMGB1 on phagocytosis of apoptotic neutrophils. HMGB1 was described originally as a nuclear protein involved in DNA binding and transcriptional regulation. However, HMGB1 also has an extracellular role as a potent mediator of inflammation and can diminish the uptake of apoptotic cells by phagocytes, a process called efferocytosis. To explore the mechanism responsible for the ability of HMGB1 to inhibit efferocytosis, we examined the role of the C-terminal acidic tail, a region of HMGB1 that has been shown to participate in specific intramolecular interactions. Deletion of the C-terminal tail abrogated the ability of HMGB1 to decrease murine macrophage ingestion of apoptotic neutrophils and to diminish phagocytosis-induced activation of Erk and Rac-1 in macrophages. We found that RAGE plays a major role in efferocytosis, and deletion of the C-terminal tail of HMGB1 prevented binding of HMGB1 to RAGE but not to other macrophage receptors involved in efferocytosis, such as the αVβ3 integrin. Whereas HMGB1 decreased ingestion of apoptotic neutrophils significantly by alveolar macrophages under in vivo conditions in the lungs of mice, this effect was lost when the C-terminal acidic tail was absent from HMGB1. These results demonstrate that the HMGB1 C-terminal tail is responsible for the inhibitory effects of HMGB1 on phagocytosis of apoptotic neutrophils under in vitro and in vivo conditions.

To determine whether peak systolic velocity of tricuspid annular motion assessed by tissue Doppler echocardiography (Sta), a right ventricular function parameter, can discriminate patients with true- and false-positive pulse pressure variation. Pulse pressure variation is used to predict fluid responsiveness in mechanically ventilated patients. However, this parameter has been reported to be falsely positive, especially in patients with right ventricular dysfunction.A prospective study.Medical and surgical intensive care unit of a university hospital.Thirty- five mechanically ventilated patients hospitalized for24 hrs with a pulse pressure variation of12%.Doppler echocardiography (including measurement of Sta and stroke volume) was performed before and after infusion of 500 mL of colloid solution. Patients were classified into two groups according to their response to fluid infusion: responders (at least 15% increase in stroke volume) and nonresponders.Twenty-three patients (66%) were responders (true-positive group) and 12 (34%) were nonresponders (false-positive group). Before volume expansion, Sta was statistically lower in the nonresponder group (0.13 [0.04] vs. 0.20 [0.05], p = .0004). The area under the curve of the receiver operating characteristic curve was 0.87 (95% confidence interval, 0.74-1). In patients with pulse pressure variation of12%, a Sta cutoff value of 0.15 m/s discriminated between responders and nonresponders with a sensitivity of 91% (80-100) and a specificity of 83% (62-100).A Sta value of0.15 m/s seems to be an accurate parameter to detect false-positive pulse pressure variation. Echocardiography should therefore be performed before fluid infusion in patients with pulse pressure variation of12%.

Summary Background Intravascular-catheter-related infections are frequent life-threatening events in health care, but incidence can be decreased by improvements in the quality of care. Optimisation of skin antisepsis is essential to prevent short-term catheter-related infections. We hypothesised that chlorhexidine–alcohol would be more effective than povidone iodine–alcohol as a skin antiseptic to prevent intravascular-catheter-related infections. Methods In this open-label, randomised controlled trial with a two-by-two factorial design, we enrolled consecutive adults (age ≥18 years) admitted to one of 11 French intensive-care units and requiring at least one of central-venous, haemodialysis, or arterial catheters. Before catheter insertion, we randomly assigned (1:1:1:1) patients via a secure web-based random-number generator (permuted blocks of eight, stratified by centre) to have all intravascular catheters prepared with 2% chlorhexidine–70% isopropyl alcohol (chlorhexidine–alcohol) or 5% povidone iodine–69% ethanol (povidone iodine–alcohol), with or without scrubbing of the skin with detergent before antiseptic application. Physicians and nurses were not masked to group assignment but microbiologists and outcome assessors were. The primary outcome was the incidence of catheter-related infections with chlorhexidine–alcohol versus povidone iodine–alcohol in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01629550 and is closed to new participants. Findings Between Oct 26, 2012, and Feb 12, 2014, 2546 patients were eligible to participate in the study. We randomly assigned 1181 patients (2547 catheters) to chlorhexidine–alcohol (594 patients with scrubbing, 587 without) and 1168 (2612 catheters) to povidone iodine–alcohol (580 patients with scrubbing, 588 without). Chlorhexidine–alcohol was associated with lower incidence of catheter-related infections (0·28 vs 1·77 per 1000 catheter-days with povidone iodine–alcohol; hazard ratio 0·15, 95% CI 0·05–0·41; p=0·0002). Scrubbing was not associated with a significant difference in catheter colonisation (p=0·3877). No systemic adverse events were reported, but severe skin reactions occurred more frequently in those assigned to chlorhexidine–alcohol (27 [3%] patients vs seven [1%] with povidone iodine–alcohol; p=0·0017) and led to chlorhexidine discontinuation in two patients. Interpretation For skin antisepsis, chlorhexidine–alcohol provides greater protection against short-term catheter-related infections than does povidone iodine–alcohol and should be included in all bundles for prevention of intravascular catheter-related infections. Funding University Hospital of Poitiers, CareFusion.

High-fidelity simulation (HFS) calls heavily upon cognitive capacities and generates stress and anxiety. The objectives of this prospective, observational study were to assess trait anxiety and fear of negative evaluation (FNE) in anaesthesiology and critical care residents and appraise their state anxiety levels and cardiovascular responses during HFS training sessions.First-year anaesthesiology and critical care residents completed the French-Canadian adaptation of the State-Trait Anxiety Inventory (IASTA Y-1: state anxiety, IASTA Y-2: trait anxiety) and the French adaptation of the Fear of Negative Evaluation Scale (FNE). Their heart rate (HR) and blood pressure (BP) were assessed before and after the training session.Twenty-three residents (8 women, 15 men) were included in the study. IASTA Y-1 and Y-2 scores were low (respectively 40.2±9.9 and 39.7±8) and FNE scores were moderate (16.7±5.5). HR measurements before and after the training sessions were significantly higher than at rest (respectively 78±19, 80±17 and 63±9b/min; P0.001). BP measurements before and after the HFS sessions were not significantly different. The IASTA Y-2 and FNE scores of female residents were significantly higher than those of male residents (respectively P=0.004 and P=0.049).First-year anaesthesiology and critical care residents had low trait anxiety and FNE. HFS training increased their HR but not their BP. Their state anxiety also remained low. Several differences between individuals were noted, particularly between men and women.

International audience; Since the implementation of two French laws in 2002 and 2005 and the implementation of guidelines about End-of-Life (EoL) decisions, few studies concerning EoL practices in French intensive care units (ICUs) have been reported. This study was aimed at assessing compliance with recommendations and current legislation concerning EoL decisions. Prospective observational study based on 1-day audit conducted from January to May 2009 in 66 southern French ICUs. Six hundred and twenty-five patients were included (median age: 63 [52-76] years, median SAPS II: 46 [34-58]). The written designation of a surrogate decision-maker was reported for 87 (15%) patients. Advance directives were completed for only 4% of patients. The EoL decision-making process consisted in a multidisciplinary approach for 99 (47%) patients and was recorded in the medical chart for 63 (64%) cases. Families were informed about medical decisions in 58% of cases. This proportion was higher (87%) if a decision to forego life-sustaining therapy was made. EoL decisions consisted of withholding treatments for 72 (94%) patients and withdrawal of treatments for 5 (6%) patients. In the multivariate stepwise logistic regression, four variables were independently associated with a decision to forego life support: preexisting dependence on others (P

Introduction Patients with advanced chronic obstructive pulmonary disease (COPD) are at risk for developing invasive pulmonary aspergillosis. A clinical algorithm has been validated to discriminate colonization from putative invasive pulmonary aspergillosis (PIPA) in Aspergillus-positive respiratory tract cultures of critically ill patients. We focused on critically ill patients with COPD who met the criteria for PIPA. Methods This matched cohort study included critically ill patients with COPD from two university hospital intensive care units (ICUs). We studied the risk factors for PIPA as well as the impact of PIPA on short- and long-term outcomes. Whether PIPA was associated with a pattern of bacterial colonization and/or infection 6 months before and/or during ICU stay was assessed. In addition, antifungal strategies were reviewed. Results Fifty cases of PIPA in critically ill patients with COPD in the ICU were matched with one hundred control patients with COPD. The ICU short- and the long-term (at 1 year) mortality were significantly increased in the PIPA group (p p p = 0.004 and p Conclusions PIPA was a strong death predictor in critically ill patients with COPD. The use of corticosteroids and antibiotics before ICU admission was a risk factor for PIPA. PIPA was not associated with a specific bacterial pattern of colonization or infection. Prompting antifungal treatment in critically ill patients with COPD who have PIPA may not be the only factor involved in prognosis reversal.

Pyelonephritides are frequently encountered diagnosis in Emergency Departments. Urinalyses have a central place in the management of this situation but the usefulness of blood cultures is not clear. We conducted a single-center retrospective study of 24 months to study the microbiological relevance of blood cultures in pyelonephritis. We included patients with blood cultures (BC) and urine cultures (UC) drawn at the same time, if they were not exposed to antibiotics prior to these tests. Of our 264 patients, 39 (15 %) had no bacteriological documentation. There were 83 (31 %) bacteremic patients. Seven patients had contaminated or sterile UC with positive BC. Four patients had positive UC and BC with the latter allowing identification of a pathogen absent from the UC (n = 1) or identifying the main pathogen in three cases. A total of 11 patients theoretically benefited from BC representing 4.2 % of our population. Excluding one patient who was known to be infected with multi-drug resistant bacteria, all empirical antibiotics regimens were effective against the identified pathogens. We did not reveal any significant therapeutic impact of blood cultures in the management of pyelonephritis, when BC and UC are performed before any antimicrobials treatment.

From the Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Service d’Anesth esie et R eanimation M edicale et Chirurgicale, Centre Hospitalier Lyon Sud, Service d’Accueil des Urgences, and Centre Hospitalier Lyon Sud, Service de Chirurgie G en erale, Digestive et Endocrinienne, Pierre-B enite; and Universit e Lyon 1, UFR Facult e de M edecine Lyon Sud-Charles M erieux, Unit e de Recherche 3738, Oullins, France

Bacterial parotitis is a common childhood disease with a favorable outcome. Staphylococcus aureus is the most frequently involved pathogen. Clinical presentation in adult patients can be misleading, Onset occurs in patients with multiple comorbidities, making diagnosis difficult--particularly in ICU. Different pathogens are found in adults with worse outcomes observed. We report here the case of a critically ill patient and discuss diagnosis and management of bacterial parotitis.

BackgroundDirect observation has been widely used to assess interactions between healthcare workers (HCWs) and patients but is time-consuming and feasible only over short periods. We used a Radio Frequency Identification Device (RFID) system to automatically measure HCW-patient interactions.MethodsWe equipped 50 patient rooms with fixed sensors and 111 HCW volunteers with mobile sensors in two clinical wards of two hospitals. For 3 months, we recorded all interactions between HCWs and 54 patients under airborne precautions for suspected (n = 40) or confirmed (n = 14) tuberculosis. Number and duration of HCW entries into patient rooms were collected daily. Concomitantly, we directly observed room entries and interviewed HCWs to evaluate their self-perception of the number and duration of contacts with tuberculosis patients.ResultsAfter signal reconstruction, 5490 interactions were recorded between 82 HCWs and 54 tuberculosis patients during 404 days of airborne isolation. Median (interquartile range) interaction duration was 2.1 (0.8-4.4) min overall, 2.3 (0.8-5.0) in the mornings, 1.8 (0.8-3.7) in the afternoons, and 2.0 (0.7-4.3) at night (PConclusionsThe RFID was well accepted by HCWs. This original technique holds promise for accurately and continuously measuring interactions between HCWs and patients, as a less resource-consuming substitute for direct observation. The results could be used to model the transmission of significant pathogens. HCW perceptions of interactions with patients accurately reflected reality.

Storage of cisatracurium at room temperature seems to have no effect on its degradation in vitro contrary to the recommendations of storage at +4°C. The purpose of this study was to evaluate the influence of cisatracurium' s storage temperature on its onset time.Prospective, randomized, double-blind trial study.Thirty patients were enrolled. The control group consisted of 15 patients receiving cisatracurium (0.15mg/kg) stored at room temperature and the intervention consisted of 15 patients receiving cisatracurium (0.15mg/kg) stored at +4°C. The primary endpoint was to compare cisatracurium onset time depending on the storage temperature.Cisatracurium onset time was 235 (180-292) seconds in the "room temperature" group vs. 240 (210-292) seconds in the "refrigerated" group. There was no difference between the onset of cisatracurium depending on the temperature of storage (p=0.51). Subgroups analysis in the "room temperature" group did not show any difference in cisatracurium onset depending on whether it was stored at room temperature for one, two or three weeks. Excellent intubation score was obtained for 100% of the patients.This study demonstrated that cisatracurium's storage at room temperature had no influence on its onset time. It provides an argument for the preservation of cisatracurium at room temperature for a period not exceeding 21 days. Monitoring the onset of curarization may increase the quality score of intubation.

To examine whether the effect of hypoxia-hypotension (HH) after traumatic brain injury (TBI) is affected by the delay between insults. Thirty Sprague-Dawley rats were randomized into five groups: sham, TBI alone (trauma alone, impact-acceleration, 450 g weight drop from 1.8 m), HH alone (blood depletion, mean arterial pressure 40 mmHg, FIO2 = 10%, 15 min), TBI + early HH (TBI followed by HH, 45-min delay), and TBI + late HH (225-min delay). Cerebral perfusion pressure was continuously recorded. Brain microdialysis and PtiO2 probes were inserted stereotaxically into the right thalamus. After the HH period and for 60 min a significant increase in cerebral lactate-pyruvate ratio was observed in groups subjected to HH vs. TBI alone and sham groups (33.0 ± 5.1 for HH alone and 51.9 ± 6.7 for TBI + early HH vs. 16.7 ± 2.4 for TBI alone at the same time, 27.6 ± 4.4 for TBI + late HH vs. 13.1 ± 1 for TBI alone at the same time). There was no significant difference in lactate-pyruvate ratio peaks between HH alone and TBI + late HH while it was higher in TBI + early HH. Similar results were obtained for cerebral glycerol. PtiO2 during HH phase did not differ between HH alone, TBI + early HH and TBI + late HH (respectively, 4.2 ± 3.1, 4.9 ± 5.7, and 2.9 ± 1.8 mmHg). A 45-min delay between HH and TBI has important metabolic consequences while a 225-min delay has a similar effect as HH in a noninjured brain. The posttraumatic brain vulnerability to HH depends on the delay between cerebral aggressions.

Malignant pleural mesothelioma represents a rare disease, for which chemotherapy actually remains unsatisfactory. From August 1998 to November 2001, 28 chemo-radio-immunonaive patients were consecutively enrolled in the trial: 22/6 males/females; median age 63 years (range, 45-79); median ECOG PS 1 (range, 0-2). They were treated with epirubicin (100 mg/m2 iv on day 1) plus gemcitabine (1000 mg/m2 iv on days 1 and 8) every 4 weeks for 6 cycles. Patients who responded to chemotherapy (n = 6) were subsequently treated with interleukin-2 (4,500,000 IU) subcutaneously every other day, until progression. A total of 124 epirubicin-gemcitabine cycles were administered (median, 6/patient; range, 2-6). Twenty-six patients were evaluated for toxicity. According to WHO criteria, we observed grade III-IV hematological and gastrointestinal toxicity respectively in 3 patients (11%) and 1 patient (3%). No red cell transfusions were required and no toxic deaths occurred. Two patients (8%) could not be evaluated for response (no therapy performed). According to WHO criteria, the final responses were: partial in 4 patients (14%), stable disease in 19 patients (69%), and progression in 3 patients (10%). In 26 patients, the median survival was 55 weeks (range, 7-222) and median time to progression 30 weeks (range, 4-156). At the time of this writing, no patient is alive. The 1-year survival was 32%, 2-year survival 11%, and 4% at 3 and 4 years. All patients were at stage III, and time to progression was 58 weeks and survival 63.5 weeks, without any toxicity. This multi-center phase II clinical trial showed that epirubicin plus gemcitabine, as a first-line treatment in malignant pleural mesothelioma, has promising activity with a good tolerability profile and symptom palliation. The role of interleukin-2 in maintenance therapy for malignant pleural mesothelioma is encouraging and requires further study.

Introduction Septic syndromes remain the leading cause of mortality in intensive care units (ICU). Septic patients rapidly develop immune dysfunctions, the intensity and duration of which have been linked with deleterious outcomes. Decreased mRNA expressions of major histocompatibility complex (MHC) class II-related genes have been reported after sepsis. We investigated whether their mRNA levels in whole blood could predict mortality in septic shock patients. Methods A total of 93 septic shock patients were included. On the third day after shock, the mRNA expressions of five MHC class II-related genes (CD74, HLA-DRA, HLA-DMB, HLA-DMA, CIITA) were measured by qRT-PCR and monocyte human leukocyte antigen-DR (mHLA-DR) by flow cytometry. Results A significant correlation was found among MHC class II related gene expressions. Among mRNA markers, the best prognostic value was obtained for CD74 (HLA-DR antigen-associated invariant chain). For this parameter, the area under the receiver operating characteristic curve (AUC) was calculated (AUC = 0.67, 95% confidence interval (CI) = 0.55 to 0.79; P = 0.01) as well as the optimal cut-off value. After stratification based on this threshold, survival curves showed that a decreased CD74 mRNA level was associated with increased mortality after septic shock (Log rank test, P = 0.0043, Hazard Ratio = 3.0, 95% CI: 1.4 to 6.5). Importantly, this association remained significant after multivariate logistic regression analysis including usual clinical confounders (that is, severity scores, P = 0.026, Odds Ratio = 3.4, 95% CI: 1.2 to 9.8). Conclusion Decreased CD74 mRNA expression significantly predicts 28-day mortality after septic shock. After validation in a larger multicentric study, this biomarker could become a robust predictor of death in septic patients.

OBJECTIVES The aim of this study was to describe the 30-day mortality rate of patients aged 80 years and older undergoing surgical and nonsurgical procedures under anaesthesia in Europe and to identify risk factors associated with mortality. DESIGN A prospective cohort study. SETTING European multicentre study, performed from October 2017 to December 2018. Centres committed to a 30-day recruitment period within the study period. PATIENTS Nine thousand four hundred and ninety-seven consecutively recruited patients aged 80 years and older undergoing any kind of surgical or nonsurgical procedures under anaesthesia. MAIN OUTCOME MEASURES The primary outcome was all-cause mortality within 30 days after procedure described by Kaplan–Meier curves with 95% CI. Risk factors for 30-day mortality were analysed using a Cox regression model with 14 fixed effects and a random centre effect. RESULTS Data for 9497 patients (median age, 83.0 years; 52.8% women) from 177 academic and nonacademic hospitals in 20 countries were analysed. Patients presented with multimorbidity (77%), frailty (14%) and at least partial functional dependence (38%). The estimated 30-day mortality rate was 4.2% (95% CI 3.8 to 4.7). Among others, independent risk factors for 30-day mortality were multimorbidity, hazard ratio 1.87 (95% CI 1.26 to 2.78), frailty, hazard ratio 2.63 (95% CI 2.10 to 3.30), and limited mobility, hazard ratio 2.19 (95% CI 1.24 to 3.86). The majority of deaths (76%) occurred in hospital. Mortality risk for unplanned ICU admission was higher, hazard ratio 3.57 (95% CI 2.38 to 5.26) than for planned ICU admission, hazard ratio 1.92 (95% CI 1.47 to 2.50). Compared with other studies, the in-hospital complication rates of 17.4 and 3.9% after discharge were low. Admission to a unit with geriatric care within 30 days after the intervention was associated with a better survival within the first 10 days. CONCLUSIONS The estimated 30-day mortality rate of 4.2% was lower than expected in this vulnerable population. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT03152734, https://clinicaltrials.gov. ispartof: European Journal Of Anaesthesiology vol:39 issue:3 pages:198-209 ispartof: location:England status: published