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Abstract Background Cardiac arrest remains a global health issue with limited data on long-term outcomes, particularly regarding recurrent cardiovascular events in patients surviving out-of-hospital cardiac arrest. (OHCA). We aimed to describe the long-term occurrence of major cardiac event defined by hospital admission for cardiovascular events or death in OHCA hospital survivors, whichever came first. Our secondary objective were to assess separately occurrence of hospital admission and death, and to identify the factors associated with major event occurrence. We hypothesized that patients surviving an OHCA has a protracted increased risk of cardiovascular events, due to both presence of the baseline conditions that lead to OHCA, and to the cardiovascular consequences of OHCA induced acute ischemia-reperfusion. Methods Consecutive OHCA patients from three hospitals of Sudden Death Expertise Center (SDEC) Registry, discharged alive from 2011 to 2015 were included. Long-term follow-up data were obtained using national inter-regime health insurance information system (SNIIRAM) database and the national French death registry. The primary endpoint was occurrence of a major event defined by hospital admission for cardiovascular events and death, whichever came first during the follow-up. The starting point of the time-to-event analysis was the date of hospital discharge. The follow-up was censored on the date of the first event. For patients without event, follow-up was censored on the date of December, 29th, 2016. Results A total of 306 patients (mean age 57; 77% male) were analyzed and followed over a median follow-up of 3 years for hospital admission for cardiovascular event and 6 years for survival. During this period, 38% patients presented a major event. Hospital admission for cardiovascular events mostly occurred during the first year after the OHCA whereas death occurred more linearly during the all period. A previous history of chronic heart failure and coronary artery disease were independently associated with the occurrence of major event (HR 1.75, 95%CI[1.06-2.88] and HR 1.70, 95%CI[1.11-2.61], respectively), whereas post-resuscitation myocardial dysfunction, cardiogenic shock and cardiologic cause of cardiac arrest did not. Conclusion Survivors from OHCA must to be considered at high risk of cardiovascular event occurrence whatever the etiology, mainly during the first year following the cardiac arrest and should require closed monitoring.

Adherence of Bacillus cereus spores to dairy industry equipment is a serious problem, causing food spoilage and, occasionally, outbreaks of foodborne diseases. Antimicrobial essential oils (EOs) have been proposed as an alternative to synthetic disinfectants due to their environmentally friendly properties. The aim of this study was to assess the effect of Cymbopogon winterianus and Juniperus phoenicea EOs on planktonic and adherent B. cereus spores to stainless steel surfaces. Eleven strains of B. cereus were used in this study. The chemical composition of the C. winterianus and J. phoenicea oils was analyzed by gas chromatography (GC)/mass spectrometry (MS). Ninety components were identified for C. winterianus, being geranial (37 %), neral (29 %), beta-myrcene (16 %) and geraniol (4 %) the most abundant constituents. Twelve components were identified for J. phoenicea, being alpha-pinene (65 %) the most abundant constituent. The results of the minimal inhibitory concentration and minimal bactericidal concentration revealed that C. winterianus was the most effective EO (p

Abstract Background The COVID-19 pandemic has highlighted the importance of intensive care units (ICUs) and their organization in healthcare systems. However, ICU capacity and availability are ongoing concerns beyond the pandemic, particularly due to an aging population and increasing complexity of care. This study aimed to assess the current and future shortage of ICU physicians in France, ten years after a previous evaluation. A national e-survey was conducted among French ICUs in January 2022 to collect data on ICU characteristics, medical staffing, individual physician characteristics, and education and training capacities. Results Among 290 ICUs contacted, 242 responded (response rate: 83%), representing 4943 ICU beds. The survey revealed an overall of 300 full time equivalent (FTE) ICU physician vacancies in the country. Nearly two-thirds of the participating ICUs reported at least one physician vacancy and 35% relied on traveling physicians to cover shifts. The ICUs most affected by physician vacancies were the ICUs of non-university affiliated public hospitals. The retirements expected in the next five years represented around 10% of the workforce. The median number of physicians per ICU was 7.0, corresponding to a ratio of 0.36 physician (FTE) per ICU bed. In addition, 27% of ICUs were at risk of critical dysfunction or closure due to vacancies and impending retirements. Conclusion The findings highlight the urgent need to address the shortage of ICU physicians in France. Compared to a similar study conducted in 2012, the inadequacy between ICU physician supply and demand has increased, resulting in a higher number of vacancies. Our study suggests that, among others, increasing the number of ICM residents trained each year could be a crucial step in addressing this issue. Failure to take appropriate measures may lead to further closures of ICUs and increased risks to patients in this healthcare system.

Background: Despite advances in asthma treatments, severe asthma exacerbation (SAE) remains a life-threatening condition in adults, and there is a lack of data derived from adult patients admitted to intensive care units (ICUs) for SAE. The current study investigated changes in adult patient characteristics, management, and outcomes of SAE over a 20-year period in 40 ICUs in the greater Paris area. Methods: In this retrospective observational study, admissions to 40 ICUs in the greater Paris area for SAE from January 1, 1997, to December 31, 2016 were analyzed. The primary outcome was the proportion of ICU admissions for SAE during 5-year periods. Secondary outcomes were ICU and hospital mortality, and the use of mechanical ventilation and catecholamine. Multivariate analysis was performed to assess factors associated with ICU mortality. Results: A total of 7049 admissions for SAE were recorded. For each 5-year period, the proportion decreased over time, with SAE accounting for 2.84% of total ICU admissions (n=2841) between 1997 and 2001, 1.76% (n=1717) between 2002 and 2006, 1.05% (n=965) between 2007 and 2011, and 1.05% (n=1526) between 2012 and 2016. The median age was 46 years (interquartile range [IQR]: 32–59 years), 55.41% were female, the median Simplified Acute Physiology Score II was 20 (IQR: 13–28), and 19.76% had mechanical ventilation. The use of mechanical ventilation remained infrequent throughout the 20-year period, whereas the use of catecholamine decreased. ICU and hospital mortality rates decreased. Factors associated with ICU mortality were renal replacement therapy, catecholamine, cardiac arrest, pneumothorax, acute respiratory distress syndrome, sepsis, and invasive mechanical ventilation (IMV). Non-survivors were older, had more severe symptoms, and were more likely to have received IMV. Conclusion: ICU admission for SAE remains uncommon, and the proportion of cases decreased over time. Despite a slight increase in symptom severity during a 20-year period, ICU and hospital mortality decreased. Patients requiring IMV had a higher mortality rate.

Abstract Cardiogenic shock (CS) is characterized by low cardiac output and sustained tissue hypoperfusion that may result in end-organ dysfunction and death. CS is associated with high short-term mortality, and its management remains challenging despite recent advances in therapeutic options. Timely diagnosis and multidisciplinary team-based management have demonstrated favourable effects on outcomes. We aimed to review evidence-based practices for managing patients with ischemic and non-ischemic CS, detailing the multi-organ supports needed in this critically ill patient population.

A convenient and effective synthesis of imidazo[1,2-a]pyrimidine derivatives has been developed under microwave irradiations using Al2O3 as a catalyst in solvent-free conditions. The functionalized imidazo[1,2-a]pyrimidine derivatives are useful in biochemistry and medical science. In our investigation, the antimicrobial activity of the synthesized compounds was evaluated against 13 microorganisms, including 6 Gram-positive bacteria, 4 Gram-negative bacteria, and 3 pathogenic fungi. Bioactivity tests revealed that the majority of the compounds exhibited good antimicrobial activity. Finally, molecular docking simulations and ADME-T predictions were performed, showing that the most active compounds have good binding modes with microbial targets and promising pharmacokinetic safety profiles.

Abstract Background Out-of-hospital cardiac arrest (OHCA) is a heterogeneous entity with multiple origins and prognoses. An early, reliable assessment of the prognosis is useful to adapt therapeutic strategy, tailor intensity of care, and inform relatives. We aimed primarily to undertake a prospective multicentric study to evaluate predictive performance of the Cardiac Arrest Prognosis (CAHP) Score as compare to historical dataset systematically collected after OHCA (Utstein style criteria). Our secondary aim was to evaluate other dedicated scores for predicting outcome after OHCA and to compare them to Utstein style criteria. Methods We prospectively collected data from 24 French and Belgium Intensive Care Units (ICUs) between August 2020 and June 2022. All cases of non-traumatic OHCA (cardiac and non-cardiac causes) patients with stable return of spontaneous circulation (ROSC) and comatose at ICU admission (defined by Glasgow coma score ≤ 8) on ICU admission were included. The primary outcome was the modified Rankin scale (mRS) at day 90 after cardiac arrest, assessed by phone interviews. A wide range of developed scores (CAHP, OHCA, CREST, C-Graph, TTM, CAST, NULL-PLEASE, and MIRACLE2) were included, and their accuracies in predicting poor outcome at 90 days after OHCA (defined as mRS ≥ 4) were determined using the area under the receiving operating characteristic curve (AUROC) and the calibration belt. Results During the study period, 907 patients were screened, and 658 were included in the study. Patients were predominantly male (72%), with a mean age of 61 ± 15, most having collapsed from a supposed cardiac cause (64%). The mortality rate at day 90 was 63% and unfavorable neurological outcomes were observed in 66%. The performance (AUROC) of Utstein criteria for poor outcome prediction was moderate at 0.79 [0.76–0.83], whereas AUROCs from other scores varied from 0.79 [0.75–0.83] to 0.88 [0.86–0.91]. For each score, the proportion of patients for whom individual values could not be calculated varied from 1.4% to 17.4%. Conclusions In patients admitted to ICUs after a successfully resuscitated OHCA, most of the scores available for the evaluation of the subsequent prognosis are more efficient than the usual Utstein criteria but calibration is unacceptable for some of them. Our results show that some scores (CAHP, sCAHP, mCAHP, OHCA, rCAST) have superior performance, and that their ease and speed of determination should encourage their use. Trial registration https://clinicaltrials.gov/ct2/show/NCT04167891

The role of the beta-adrenergic signaling pathway in heart failure (HF) is pivotal. Early blockade of this pathway with beta-blocker (BB) therapy is recommended as the first-line medication for patients with HF and reduced ejection fraction (HFrEF). Conversely, in patients with severe acute HF (AHF), including those with resolved cardiogenic shock (CS), BB initiation can be hazardous. There are very few data on the management of BB in these situations. The present expert consensus aims to review all published data on the use of BB in patients with severe decompensated AHF, with or without hemodynamic compromise, and proposes an expert-recommended practical algorithm for the prescription and monitoring of BB therapy in critical settings.

Abstract Background Severe hypothyroidism (SH) is a rare but life-threatening endocrine emergency. Only a few data are available on its management and outcomes of the most severe forms requiring ICU admission. We aimed to describe the clinical manifestations, management, and in-ICU and 6-month survival rates of these patients. Methods We conducted a retrospective, multicenter study over 18 years in 32 French ICUs. The local medical records of patients from each participating ICU were screened using the International Classification of Disease 10th revision. Inclusion criteria were the presence of biological hypothyroidism associated with at least one cardinal sign among alteration of consciousness, hypothermia and circulatory failure, and at least one SH-related organ failure. Results Eighty-two patients were included in the study. Thyroiditis and thyroidectomy represented the main SH etiologies (29% and 19%, respectively), while hypothyroidism was unknown in 44 patients (54%) before ICU admission. The most frequent SH triggers were levothyroxine discontinuation (28%), sepsis (15%), and amiodarone-related hypothyroidism (11%). Clinical presentations included hypothermia (66%), hemodynamic failure (57%), and coma (52%). In-ICU and 6-month mortality rates were 26% and 39%, respectively. Multivariable analyses retained age > 70 years [odds ratio OR 6.01 (1.75–24.1)] Sequential Organ-Failure Assessment score cardiovascular component ≥ 2 [OR 11.1 (2.47–84.2)] and ventilation component ≥ 2 [OR 4.52 (1.27–18.6)] as being independently associated with in-ICU mortality. Conclusions SH is a rare life-threatening emergency with various clinical presentations. Hemodynamic and respiratory failures are strongly associated with worse outcomes. The very high mortality prompts early diagnosis and rapid levothyroxine administration with close cardiac and hemodynamic monitoring.

Venoarterial extracorporeal membrane oxygenation (VA ECMO) is a form of temporary mechanical circulatory support and simultaneous extracorporeal gas exchange for acute cardiorespiratory failure, including refractory cardiogenic shock (CS) and cardiac arrest (CA). Few studies have assessed predictors of successful weaning (SW) from VA ECMO. This systematic review and meta-analysis aimed to identify a multiparameter strategy associated with SW from VA ECMO. PubMed and the Cochrane Library and the International Clinical Trials Registry Platform were searched. Studies reporting adult patients with CS or CA treated with VA ECMO published from the year 2000 onwards were included. Primary outcomes were hemodynamic, laboratory, and echocardiography parameters associated with a VA ECMO SW. A total of 11 studies (n=653) were included in this review. Pooled VA ECMO SW was 45% (95%CI: 39–50%, I2 7%) and in-hospital mortality rate was 46.6% (95%CI: 33–60%; I2 36%). In the SW group, pulse pressure [MD 12.7 (95%CI: 7.3–18) I2 = 0%] and mean blood pressure [MD 20.15 (95%CI: 13.8–26.4 I2 = 0) were higher. They also had lower values of creatinine [MD –0.59 (95%CI: –0.9 to –0.2) I2 = 7%], lactate [MD –3.1 (95%CI: –5.4 to –0.7) I2 = 89%], and creatine kinase [–2779.5 (95%CI: –5387 to –171) I2 = 38%]. And higher left and right ventricular ejection fraction, MD 17.9% (95%CI: –0.2–36.2) I2 = 91%, and MD 15.9% (95%CI 11.9–20) I2 = 0%, respectively. Different hemodynamic, laboratory, and echocardiographic parameters were associated with successful device removal. This systematic review demonstrated the relationship of multiparametric assessment on VA ECMO SW.

Abstract The use of veno-arterial extracorporeal membrane oxygenation (VA ECMO) for the treatment of refractory cardiogenic shock has increased significantly. Nevertheless, early weaning may be advisable to reduce the potential for severe complications. Only a few studies focusing on ECMO weaning predictors are currently available. Our objective was to evaluate factors that may help predict failure during VA ECMO weaning. We included 57 patients on VA ECMO support previously considered suitable for weaning based on specific criteria. Clinical, haemato-chemical and echocardiographic assessment was considered before and after a “weaning test” (ECMO flow 7 days (OR 24 [2–269]) were predictors of weaning failure. The VA ECMO weaning test failed in less than 40% of patients considered suitable for weaning. Clinical and echocardiographic criteria, which are easily accessible by a non-expert intensivist, may help increase the probability of successful weaning.

Abstract In our recent survey, we aimed to collect information on perceived inequity as well as professional and personal fulfillment among women intensivists in France. For the 371 respondents out of the 732 persons who received the survey, the findings were unequivocal: for one-third of the respondents, being a woman was considered as an obstacle to careers or academic advancement, and for two thirds, pregnancy was viewed as a barrier to their career advancement. Gender discrimination had been experienced by 55% of the respondents. In 2019, to promote and achieve gender equity in the French Intensive Care Society (FICS), ten actions were initiated and are detailed in the present manuscript together with supporting data: (1) creation of a working group: the FEMMIR group; (2) promotion of mentorship; (3) implementation of concrete sponsorship; (4) transparency and public reporting of gender ratios in editorial boards; (5) workshops dedicated to unconscious gender bias; (6) workshops dedicated to improved women assertiveness; (7) role models; (8) creation of educational/information programs for young intensivists; (9) development of research on gender inequity and, as a perspective; and (10) development of a wide-ranging program. This review is aimed at providing a toolbox of organizational best practices designed to achieve gender equity. It is particularly important to share promising practical action engaged in our FEMMIR group with other concerned professionals around the world.

Abstract Aims Published data on cardiogenic shock (CS) are scarce and are mostly focused on small registries of selected populations. The aim of this study was to examine the current CS picture and define the independent correlates of 30 day mortality in a large non‐selected cohort. Methods and results FRENSHOCK is a prospective multicentre observational survey conducted in metropolitan French intensive care units and intensive cardiac care units between April and October 2016. There were 772 patients enrolled (mean age 65.7 ± 14.9 years; 71.5% male). Of these patients, 280 (36.3%) had ischaemic CS. Organ replacement therapies (respiratory support, circulatory support or renal replacement therapy) were used in 58.3% of patients. Mortality at 30 days was 26.0% in the overall population (16.7% to 48.0% depending on the main cause and first place of admission). Multivariate analysis showed that six independent factors were associated with a higher 30 day mortality: age [per year, odds ratio (OR) 1.06, 95% confidence interval (CI): 1.04–1.08], diuretics (OR 1.74, 95% CI: 1.05–2.88), circulatory support (OR 1.92, 95% CI: 1.12–3.29), left ventricular ejection fraction

There is an extensive body of literature focused on sepsis-induced myocardial dysfunction, but results are conflicting and no objective definition of septic cardiomyopathy (SCM) has been established. SCM may be defined as a sepsis-associated acute syndrome of non-ischemic cardiac dysfunction with systolic and/or diastolic left ventricular (LV) dysfunction and/or right ventricular dysfunction. Physicians should consider this diagnosis in patients with sepsis-associated organ dysfunction, and particularly in cases of septic shock that require vasopressors. Echocardiography is currently the gold standard for diagnosis of SCM. Left ventricular ejection fraction is the most common parameter used to describe LV function in the literature, but its dependence on loading conditions, particularly afterload, limits its use as a measure of intrinsic myocardial contractility. Therefore, repeated echocardiography evaluation is mandatory. Evaluation of global longitudinal strain (GLS) may be more sensitive and specific for SCM than LV ejection fraction (LVEF). Standard management includes etiological treatment, adapted fluid resuscitation, use of vasopressors, and monitoring. Use of inotropes remains uncertain, and heart rate control could be an option in some patients.

BackgroundCardiogenic shock (CS) is a life-threatening condition carrying poor prognosis, potentially triggered by ventricular arrhythmia (VA). Whether the occurrence of VA as trigger of CS worsens the prognosis compared to non-VA triggers remains unclear. The aim of this study was to evaluate 1-year outcomes [mortality, heart transplantation, ventricular assist devices (VAD)] between VA-triggered and non-VA-triggered CS.MethodsFRENSHOCK is a prospective multicenter registry including 772 CS patients from 49 centers. One to three triggers can be identified in the registry (ischemic, mechanical complications, ventricular/supraventricular arrhythmia, bradycardia, iatrogenesis, infection, non-compliance). Baseline characteristics, management and 1-year outcomes were analyzed according to the VA-trigger in the CS population.ResultsWithin 769 CS patients included, 94 were VA-triggered (12.2%) and were compared to others. At 1 year, although there was no mortality difference [42.6 vs. 45.3%, HR 0.94 (0.67–1.30), p = 0.7], VA-triggered CS resulted in more heart transplantations and VAD (17 vs. 9%, p = 0.02). Into VA-triggered CS group, though there was no 1-year mortality difference between ischemic and non-ischemic cardiomyopathies [42.5 vs. 42.6%, HR 0.97 (0.52–1.81), p = 0.92], non-ischemic cardiomyopathy led to more heart transplantations and VAD (25.9 vs. 5%, p = 0.02).ConclusionVA-triggered CS did not show higher mortality compared to other triggers but resulted in more heart transplantation and VAD at 1 year, especially in non-ischemic cardiomyopathy, suggesting the need for earlier evaluation by advanced heart failure specialized team for a possible indication of mechanical circulatory support or heart transplantation.Clinical trial registrationhttps://clinicaltrials.gov, identifier NCT02703038.

Abstract Background Echocardiographic parameters have been poorly investigated for estimating cardiovascular risk in patients with sepsis and new-onset atrial fibrillation. We aim to assess the prevalence of transesophageal echocardiographic abnormalities and their relationship with cardiovascular events in mechanically ventilated patients with sepsis and new-onset atrial fibrillation. Methods In this prospective multicenter pilot study, left atrial/left atrial appendage (LA/LAA) dysfunction, severe aortic atheroma, and left ventricular systolic dysfunction were assessed using an initial transesophageal echocardiographic study, which was repeated after 48–72 h to detect LA/LAA thrombus formation. The study outcome was a composite of cardiovascular events at day 28, including arterial thromboembolic events (ischemic stroke, non-cerebrovascular arterial thromboembolism, LA/LAA thrombus), major bleeding, and all-cause death. Results The study population comprised 94 patients (septic shock 63%; 35% women; median age 69 years). LA/LAA dysfunction, severe aortic atheroma, and left ventricular systolic dysfunction were detected in 17 (19%), 22 (24%), and 27 (29%) patients, respectively. At day 28, the incidence of cardiovascular events was 46% (95% confidence interval [CI]: 35 to 56). Arterial thromboembolic events and major bleeding occurred in 7 (7%) patients (5 ischemic strokes, 1 non-cerebrovascular arterial thromboembolism, 2 left atrial appendage thrombi) and 18 (19%) patients, respectively. At day 28, 27 patients (29%) died. Septic shock (hazard ratio [HR]: 2.36; 95% CI 1.06 to 5.29) and left ventricular systolic dysfunction (HR: 2.06; 95% CI 1.05 to 4.05) were independently associated with cardiovascular events. Conclusions Transesophageal echocardiographic abnormalities are common in mechanically ventilated patients with sepsis and new-onset atrial fibrillation, but only left ventricular systolic dysfunction was associated with cardiovascular events at day 28.

Abstract Background Intensive care has a strong impact on health-related quality of life (HRQOL). The specific impact of cardiac arrest in non-shockable rhythm is poorly known. Patients and methods We gathered patients included in two randomized controlled trials (AWARE and HYPERION). The HYPERION trial included ICU-treated non-shockable cardiac arrest patients. The AWARE study included ICU patients requiring mechanical ventilation. We compared the 3-months HRQOL of these patients to those of a large sample of the French general population. Physical and mental dimension were compared. Multivariable linear regression was used to pick up factors associated with HRQOL. Results 72 and 307 patients of the HYPERION and the AWARE studies were compared to 20,574 French controls. ICU patients evidenced lower scores in all the SF-36 dimensions compared to the controls. Similar scores were observed in both HYPERION and AWARe trials. The physical component score was lower in patients from the HYPERION trial compared to those from the AWARE trials and to controls (38.6 [29.6-47.8], 35.4 [27.5-46.4] vs. 53.0 [46.0-56.7], $$\hbox {p}

Abstract Background The medical workforce has been feminized for the last two decades worldwide. Nonetheless, women remain under-represented among intensivists. We conducted a survey among French women intensivists to assess their professional and personal quality of life and their perception of potential gender discrimination at work. Methods We conducted an observational descriptive study by sending a survey, designed by the group FEMMIR (FEmmes Médecins en Médecine Intensive Réanimation), to women intensivists in France, using primarily the Société de Réanimation de Langue Française (SRLF) mailing list. The questionnaire was also available online between September 2019 and January 2020 and women intensivists were encouraged to answer through email reminders. It pertained to five main domains, including demographic characteristics, work position, workload and clinical/research activities, self-fulfillment scale, perceived discrimination at work and suggested measures to implement. Results Three hundred and seventy-one women responded to the questionnaire, among whom 16% had an academic position. Being a woman intensivist and pregnancy were both considered to increase difficulties in careers’ advancement by 31% and 73% of the respondents, respectively. Almost half of the respondents (46%) quoted their quality of life equal to or lower than 6 on a scale varying from 1 (very bad quality of life) to 10 (excellent quality of life). They were 52% to feel an imbalance between their personal and professional life at the cost of their personal life. Gender discrimination has been experienced by 55% of the respondents while 37% confided having already been subject of bullying or harassment. Opportunities to adjust their work timetable including part-time work, better considerations for pregnant women including increasing the number of intensivists and the systematic replacement during maternity leave, and the respect of the law regarding the paternity leave were suggested as key measures to enable better professional and personal accomplishment by women intensivists. Conclusion In this first large French survey in women intensivists, we pointed out issues felt by women intensivists that included an imbalance between professional and personal life, a perceived loss of opportunity due to the fact of being a woman, frequent reported bullying or harassment and a lack of consideration of the needs related to pregnancy and motherhood.

Abstract Background Controversies exist on the nature of COVID-19 related acute respiratory distress syndrome (ARDS) in particular on the static compliance of the respiratory system (Crs). We aimed to analyze the association of Crs with outcome in COVID-19-associated ARDS, to ascertain its determinants and to describe its evolution at day-14. Methods In this observational multicenter cohort of patients with moderate to severe Covid-19 ARDS, Crs was measured at day-1 and day-14. Association between Crs or Crs/ideal body weight (IBW) and breathing without assistance at day-28 was analyzed with multivariable logistic regression. Determinants were ascertained by multivariable linear regression. Day-14 Crs was compared to day-1 Crs with paired t-test in patients still under controlled mechanical ventilation. Results The mean Crs in 372 patients was 37.6 ± 13 mL/cmH2O, similar to as in ARDS of other causes. Multivariate linear regression identified chronic hypertension, low PaO2/FiO2 ratio, low PEEP, and low tidal volume as associated with lower Crs/IBW. After adjustment on confounders, nor Crs [OR 1.0 (CI 95% 0.98–1.02)] neither Crs/IBW [OR 0.63 (CI 95% 0.13–3.1)] were associated with the chance of breathing without assistance at day-28 whereas plateau pressure was [OR 0.93 (CI 95% 0.88–0.99)]. In a subset of 108 patients, day-14 Crs decreased compared to day-1 Crs (31.2 ± 14.4 mL/cmH2O vs 37.8 ± 11.4 mL/cmH2O, p

Abstract Background The effect of cytomegalovirus (CMV) reactivation on the length of mechanical ventilation and mortality in immunocompetent ICU patients requiring invasive mechanical ventilation remains controversial. The main objective of this study was to determine whether preemptive intravenous ganciclovir increases the number of ventilator-free days in patients with CMV blood reactivation. Methods This double-blind, placebo-controlled, randomized clinical trial involved 19 ICUs in France. Seventy-six adults ≥ 18 years old who had been mechanically ventilated for at least 96 h, expected to remain on mechanical ventilation for ≥ 48 h, and exhibited reactivation of CMV in blood were enrolled between February 5th, 2014, and January 23rd, 2019. Participants were randomized to receive ganciclovir 5 mg/kg bid for 14 days (n = 39) or a matching placebo (n = 37). Results The primary endpoint was ventilator-free days from randomization to day 60. Prespecified secondary outcomes included day 60 mortality. The trial was stopped for futility based on the results of an interim analysis by the DSMB. The subdistribution hazard ratio for being alive and weaned from mechanical ventilation at day 60 for patients receiving ganciclovir (N = 39) compared with control patients (N = 37) was 1.14 (95% CI from 0.63 to 2.06; P = 0.66). The median [IQR] numbers of ventilator-free days for ganciclovir-treated patients and controls were 10 [0–51] and 0 [0–43] days, respectively (P = 0.46). Mortality at day 60 was 41% in patients in the ganciclovir group and 43% in the placebo group (P = .845). Creatinine levels and blood cells counts did not differ significantly between the two groups. Conclusions In patients mechanically ventilated for ≥ 96 h with CMV reactivation in blood, preemptive ganciclovir did not improve the outcome.

Abstract Background Limited data are available regarding antiviral therapy efficacy in most severe patients under mechanical ventilation for Covid-19-related acute respiratory distress syndrome (ARDS). Methods Comparison of antiviral strategies (none, hydroxychloroquine (OHQ), lopinavir/ritonavir (L/R), others (combination or remdesivir) in an observational multicentre cohort of patients with moderate-to-severe Covid-19 ARDS. The primary endpoint was the number of day 28 ventilator-free days (VFD). Patients who died before d28 were considered as having 0 VFD. The variable was dichotomized into “patients still ventilated or dead at day 28” versus “patients weaned and alive at day 28”. Results We analyzed 415 patients (85 treated with standard of care (SOC), 57 with L/R, 220 with OHQ, and 53 others). The median number of d28-VFD was 0 (IQR 0–13) and differed between groups (P = 0.03), SOC patients having the highest d28-VFD. After adjustment for age, sex, Charlson Comorbidity Index, PaO2/FiO2 ratio and plateau pressure and accounting for center effect with a generalized linear mixed model, none of the antiviral strategies increased the chance of being alive and weaned from MV at day 28 compared to the SOC strategy (OR 0.48 CI95% (0.18–1.25); OR 0.96 (0.47–2.02) and OR 1.43 (0.53–4.04) for L/R, OHQ and other treatments, respectively). Acute kidney injury during ICU stay was frequent (55%); its incidence was higher in patients receiving lopinavir (66 vs 53%, P = 0.03). After adjustment for age, sex, BMI, chronic hypertension and chronic renal disease, the use of L/R was associated with an increased risk of renal replacement therapy (RRT). (OR 2.52 CI95% 1.16–5.59). Conclusion In this multicentre observational study of moderate-to-severe Covid-19 ARDS patients, we did not observe any benefit among patients treated with OHQ or L/R compared with SOC. The use of L/R treatment was associated with an increased need for RRT. Take home message Neither hydroxychloroquine nor lopinavir/ritonavir as COVID-19 antiviral treatment is associated with higher ventilator-free days at day 28 when compared with standard of care (no antiviral treatment) in ICU patients under invasive mechanical ventilation. Lopinavir/ritonavir is associated with an increased risk of renal replacement therapy requirement. Tweet COVID-19: Insights from ARDS cohort: no signal of efficacy of any antiviral drugs. Lopinavir/ritonavir may be associated with need for RRT

Abstract Purpose Recent doubts regarding the efficacy may have resulted in a loss of interest for targeted temperature management (TTM) in comatose cardiac arrest (CA) patients, with uncertain consequences on outcome. We aimed to identify a change in TTM use and to assess the relationship between this change and neurological outcome. Methods We used Utstein data prospectively collected in the Sudden Death Expertise Center (SDEC) registry (capturing CA data from all secondary and tertiary hospitals located in the Great Paris area, France) between May 2011 and December 2017. All cases of non-traumatic OHCA patients with stable return of spontaneous circulation (ROSC) were included. After adjustment for potential confounders, we assessed the relationship between changes over time in the use of TTM and neurological recovery at discharge using the Cerebral Performance Categories (CPC) scale. Results Between May 2011 and December 2017, 3925 patients were retained in the analysis, of whom 1847 (47%) received TTM. The rate of good neurological outcome at discharge (CPC 1 or 2) was higher in TTM patients as compared with no TTM (33% vs 15%, P

Abstract Background The Artificial Kidney Initiation in Kidney Injury (AKIKI) trial showed that a delayed renal replacement therapy (RRT) strategy for severe acute kidney injury (AKI) in critically ill patients was safe and associated with major reduction in RRT initiation compared with an early strategy. The five criteria which mandated RRT initiation in the delayed arm were: severe hyperkalemia, severe acidosis, acute pulmonary edema due to fluid overload resulting in severe hypoxemia, serum urea concentration > 40 mmol/l and oliguria/anuria > 72 h. However, duration of anuria/oliguria and level of blood urea are still criteria open to debate. The objective of the study is to compare the delayed strategy used in AKIKI (now termed “standard”) with another in which RRT is further delayed for a longer period (termed “delayed strategy”). Methods/design This is a prospective, multicenter, open-label, two-arm randomized trial. The study is composed of two stages (observational and randomization stages). At any time, the occurrence of a potentially severe condition (severe hyperkalemia, severe metabolic or mixed acidosis, acute pulmonary edema due to fluid overload resulting in severe hypoxemia) suggests immediate RRT initiation. Patients receiving (or who have received) intravenously administered catecholamines and/or invasive mechanical ventilation and presenting with AKI stage 3 of the KDIGO classification and with no potentially severe condition are included in the observational stage. Patients presenting a serum urea concentration > 40 mmol/l and/or an oliguria/anuria for more than 72 h are randomly allocated to a standard (RRT is initiated within 12 h) or a delayed RRT strategy (RRT is initiated only if an above-mentioned potentially severe condition occurs or if the serum urea concentration reaches 50 mmol/l). The primary outcome will be the number of RRT-free days at day 28. One interim analysis is planned. It is expected to include 810 patients in the observational stage and to randomize 270 subjects. Discussion The AKIKI2 study should improve the knowledge of RRT initiation criteria in critically ill patients. The potential reduction in RRT use allowed by a delayed RRT strategy might be associated with less invasive care and decreased costs. Enrollment is ongoing. Inclusions are expected to be completed by November 2019. Trial registration ClinicalTrials.gov, ID: NCT03396757. Registered on 11 January 2018.

Introduction International guidelines include early nutritional support (≤48 hour after admission), 20–25 kcal/kg/day, and 1.2–2 g/kg/day protein at the acute phase of critical illness. Recent data challenge the appropriateness of providing standard amounts of calories and protein during acute critical illness. Restricting calorie and protein intakes seemed beneficial, suggesting a role for metabolic pathways such as autophagy, a potential key mechanism in safeguarding cellular integrity, notably in the muscle, during critical illness. However, the optimal calorie and protein supply at the acute phase of severe critical illness remains unknown. NUTRIREA-3 will be the first trial to compare standard calorie and protein feeding complying with guidelines to low-calorie low-protein feeding. We hypothesised that nutritional support with calorie and protein restriction during acute critical illness decreased day 90 mortality and/or dependency on intensive care unit (ICU) management in mechanically ventilated patients receiving vasoactive amine therapy for shock, compared with standard calorie and protein targets.Methods and analysis NUTRIREA-3 is a randomised, controlled, multicentre, open-label trial comparing two parallel groups of patients receiving invasive mechanical ventilation and vasoactive amine therapy for shock and given early nutritional support according to one of two strategies: early calorie-protein restriction (6 kcal/kg/day-0.2–0.4 g/kg/day) or standard calorie-protein targets (25 kcal/kg/day, 1.0–1.3 g/kg/day) at the acute phase defined as the first 7 days in the ICU. We will include 3044 patients in 61 French ICUs. Two primary end-points will be evaluated: day 90 mortality and time to ICU discharge readiness. The trial will be considered positive if significant between-group differences are found for one or both alternative primary endpoints. Secondary outcomes include hospital-acquired infections and nutritional, clinical and functional outcomes.Ethics and dissemination The NUTRIREA-3 study has been approved by the appropriate ethics committee. Patients are included after informed consent. Results will be submitted for publication in peer-reviewed journals.Trial registration number NCT03573739.

Objectives: Different phenotypes have been identified in acute respiratory distress syndrome (ARDS). Existence of several phenotypes in coronavirus disease (COVID-19) related acute respiratory distress syndrome is unknown. We sought to identify different phenotypes of patients with moderate to severe ARDS related to COVID-19.Methods: We conducted an observational study of 416 COVID-19 patients with moderate to severe ARDS at 21 intensive care units in Belgium and France. The primary outcome was day-28 ventilatory free days. Secondary outcomes were mortality on day 28, acute kidney injury, acute cardiac injury, pulmonary embolism, and deep venous thrombosis. Multiple factor analysis and hierarchical classification on principal components were performed to distinguish different clinical phenotypes.Results: We identified three different phenotypes in 150, 176, and 90 patients, respectively. Phenotype 3 was characterized by short evolution, severe hypoxemia, and old comorbid patients. Phenotype 1 was mainly characterized by the absence of comorbidities, relatively high compliance, and long duration of symptoms, whereas phenotype 2 was characterized female sex, and the presence of mild comorbidities such as uncomplicated diabetes or chronic hypertension. The compliance in phenotype 2 was lower than that in phenotype 1, with higher plateau and driving pressure. Phenotype 3 was associated with higher mortality compared to phenotypes 1 and 2.Conclusions: In COVID-19 patients with moderate to severe ARDS, we identified three clinical phenotypes. One of these included older people with comorbidities who had a fulminant course of disease with poor prognosis. Requirement of different treatments and ventilatory strategies for each phenotype needs further investigation.

A new and suitable multicomponent one-pot reaction was developed for the synthesis of 2-amino-3-cyanopyridine derivatives. Background: This synthesis was demonstrated by the efficient and easy access to a variety of substituted 2-aminopyridines using enaminones as key precursors under solvent-free conditions. Methods: A range of spectroscopic techniques was used to determine and confirm the chemical structures (FTIR, 1H NMR, 13C NMR). The antimicrobial potency of synthesized compounds (2a–d) was tested using disk diffusion assays, and the Minimum Inhibitory Concentration (MIC) for the active compounds was determined against a panel of microorganisms, including Gram-positive and Gram-negative bacteria and yeasts. Moreover, a docking analysis was conducted by Molecular Operating Environment (MOE) software to provide supplementary information about the potential, as well as an ADME-T prediction to describe the pharmacokinetic properties of the best compound and its toxicity. Results: The results of the antimicrobial activity indicated that compound 2c showed the highest activity against Gram-positive bacteria, particularly S. aureus and B. subtilis whose MIC values were 0.039 ± 0.000 µg·mL−1. The results of the theoretical study of compound 2c were in line with the experimental data and exhibited excellent antibacterial potential. Conclusions: On the basis of the obtained results, compound 2c can be used as an antibacterial agent model with high antibacterial potency.

Background: Coronavirus disease 2019 (COVID-19) has been associated with cardiovascular complications and coagulation disorders.Objectives: To explore clinical and biological parameters of COVID-19 patients with hospitalization criteria that could predict referral to intensive care unit (ICU).Methods: Analyzing the clinical and biological profiles of COVID-19 patients at admission.Results: Among 99 consecutive patients that fulfilled criteria for hospitalization, 48 were hospitalized in the medicine department, 21 were first admitted to the medicine ward department and referred later to ICU, and 30 were directly admitted to ICU from the emergency department. At admission, patients requiring ICU were more likely to have lymphopenia, decreased SpO2, a D-dimer level above 1,000 ng/mL, and a higher high-sensitivity cardiac troponin (Hs-cTnI) level. A receiver operating characteristic curve analysis identified Hs-cTnI above 9.75 pg/mL as the best predictive criteria for ICU referral [area under the curve (AUC), 86.4; 95% CI, 76.6–96.2]. This cutoff for Hs-cTnI was confirmed in univariate [odds ratio (OR), 22.8; 95% CI, 6.0–116.2] and multivariate analysis after adjustment for D-dimer level (adjusted OR, 20.85; 95% CI, 4.76–128.4). Transthoracic echocardiography parameters subsequently measured in 72 patients showed an increased right ventricular (RV) afterload correlated with Hs-cTnI (r = 0.42, p = 0.010) and D-dimer (r = 0.18, p = 0.047).Conclusion: Hs-cTnI appears to be the best relevant predictive factor for referring COVID-19 patients to ICU. This result associated with the correlation of D-dimer with RV dilatation probably reflects a myocardial injury due to an increased RV wall tension. This reinforces the hypothesis of a COVID-19-associated microvascular thrombosis inducing a higher RV afterload.

Objective: To compare oral hygiene practices, education and social background, food intake and oral malodor of Algerian adults suffering from dental caries with normal controls, and to determine and compare the bacterial composition of the supragingival plaques from the above-mentioned groups. Methods: Participants completed a questionnaire and were clinically examined for dental caries using decayed, missing and filled teeth index according to the criteria laid down by the World Health Organization. Supragingival plaque samples were collected from 50 caries-free adults (CF) and 50 caries-active adults (CA). Standard procedures of culture and identification of aerobic and anaerobic bacteria were used. Data were analyzed using Chi-square test. Results: A total of 117 bacterial strains were isolated from supragingival plaques in CF group subjects, 76 (64.96%) of them belonged to 9 aerobic genera, and 41 (35.04%) to 9 anaerobic genera (P