Hydrocortisone plus Fludrocortisone for Adults with Septic Shock.

BACKGROUND: Septic shock is characterized by dysregulation of the host response to infection, with circulatory, cellular, and metabolic abnormalities. We hypothesized that therapy with hydrocortisone plus fludrocortisone or with drotrecogin alfa (activated), which can modulate the host response, would improve the clinical outcomes of patients with septic shock. METHODS: In this multicenter, double-blind, randomized trial with a 2-by-2 factorial design, we evaluated the effect of hydrocortisone-plus-fludrocortisone therapy, drotrecogin alfa (activated), the combination of the three drugs, or their respective placebos. The primary outcome was 90-day all-cause mortality. Secondary outcomes included mortality at intensive care unit (ICU) discharge and hospital discharge and at day 28 and day 180 and the number of days alive and free of vasopressors, mechanical ventilation, or organ failure. After drotrecogin alfa (activated) was withdrawn from the market, the trial continued with a two-group parallel design. The analysis compared patients who received hydrocortisone plus fludrocortisone with those who did not (placebo group). RESULTS: Among the 1241 patients included in the trial, the 90-day mortality was 43.0% (264 of 614 patients) in the hydrocortisone-plus-fludrocortisone group and 49.1% (308 of 627 patients) in the placebo group (P=0.03). The relative risk of death in the hydrocortisone-plus-fludrocortisone group was 0.88 (95% confidence interval, 0.78 to 0.99). Mortality was significantly lower in the hydrocortisone-plus-fludrocortisone group than in the placebo group at ICU discharge (35.4% vs. 41.0%, P=0.04), hospital discharge (39.0% vs. 45.3%, P=0.02), and day 180 (46.6% vs. 52.5%, P=0.04) but not at day 28 (33.7% and 38.9%, respectively; P=0.06). The number of vasopressor-free days to day 28 was significantly higher in the hydrocortisone-plus-fludrocortisone group than in the placebo group (17 vs. 15 days, P<0.001), as was the number of organ-failure-free days (14 vs. 12 days, P=0.003). The number of ventilator-free days was similar in the two groups (11 days in the hydrocortisone-plus-fludrocortisone group and 10 in the placebo group, P=0.07). The rate of serious adverse events did not differ significantly between the two groups, but hyperglycemia was more common in hydrocortisone-plus-fludrocortisone group. CONCLUSIONS: In this trial involving patients with septic shock, 90-day all-cause mortality was lower among those who received hydrocortisone plus fludrocortisone than among those who received placebo. (Funded by Programme Hospitalier de Recherche Clinique 2007 of the French Ministry of Social Affairs and Health; APROCCHSS ClinicalTrials.gov number, NCT00625209 .).

Assessment of Bacterial Colonization of Intracranial Pressure Transducers: A Prospective Study.

OBJECTIVES: Cerebral infections related to the presence of an intraparenchymal intracranial pressure transducer (ICPT) are rare. We assessed the incidence of ICPT-related infections and colonization using culture, molecular biology, and electron microscopy. METHODS: All consecutive patients in a neurosurgical intensive care unit who had an ICPT inserted between March 2017 and February 2018 were prospectively included. Presence of colonization on the ICPTs was assessed after removal using culture, scanning electron microscopy (SEM), and next-generation sequencing (NGS). RESULTS: Fifty-three ICPTs (53 patients), indwelling for a median of 4 (range 3-7) days, were studied. Median patient follow-up was 3 months. SEM, microbial culture, and NGS were performed for 91%, 79%, and 72% of ICPTs, respectively; 28 ICPTs (53%) were assessed using all three techniques. No patient developed ICPT-related infection. Microbial cultures were positive for two of the ICPTs (5%); colonization was identified on all ICPTs using NGS and SEM. Mature biofilm was observed on 35/48 (73%) of ICPTs. A median of 10 (8-12) operational taxonomic units were identified for each ICPT, most being of environmental origin. There was no association between biofilm maturity and antimicrobial treatment or duration of ICPT insertion. Antimicrobial treatment was associated with decreased alpha and beta-diversity (p = 0.01). CONCLUSIONS: We observed no ICPT-related cerebral infections although colonization was identified on all ICPTs using NGS and SEM. Mature biofilm was the main bacterial lifestyle on the ICPTs.

Durability of antimicrobial activity of antibiotic-impregnated external ventricular drains: a prospective study.

BACKGROUND: Antibiotic-impregnated external ventricular drains (AI-EVDs) have a debated efficacy in clinical studies. OBJECTIVES: Our aim was to assess the durability of antimicrobial activity of AI-EVDs used in clinical settings. METHODS: From April 2017 to January 2018, all consecutive AI-EVDs (Bactiseal™) inserted in adult patients were prospectively included. After removal, each AI-EVD was cultured and assessed for antimicrobial activity on both internal and external sides of AI-EVDs. Catheters were each challenged with a single Staphylococcus strain [MSSA, MRSA or methicillin-resistant Staphylococcus epidermidis (MRSE)]. MS was used to measure residual concentrations of rifampicin and clindamycin. RESULTS: Sixty-five AI-EVDs were included (56 patients). Among these, 21 were challenged with MSSA, 23 with MRSA and 21 with MRSE. Five ventriculostomy-related colonizations (9%) and two ventriculostomy-related infections (4%) occurred. Staphylococcus was the main bacterium responsible for colonization (4/5). AI-EVD inhibition decreased significantly against MRSA and MRSE according to duration of catheterization (for external and internal sides, P < 0.02) and overall volume of CSF drained (P < 0.005 for both sides against MRSE, P < 0.005 for external side against MRSA), but not against MSSA. Clindamycin concentration was not correlated with duration of catheterization or CSF volume drained, but <20% of initial concentration was recovered even after 5 days of AI-EVD dwelling. Conversely, rifampicin concentration showed a rapid and significant decline correlated to duration and CSF volume (P < 0.001 and P = 0.03, respectively). CONCLUSIONS: Antimicrobial activity of AI-EVDs dropped quickly in vivo. Antimicrobial impregnation did not prevent AI-EVD colonization by susceptible strains in 9% of the cases.

Dramatic Increase of Amoxicillin-Induced Crystal Nephropathy Found in a Cohort Study of French Pharmacovigilance Centers.

An increase in amoxicillin-induced crystal nephropathy (AICN) incidence has been recently suggested. The aims of this study were to investigate the trend of AICN incidence through Paris' regional centers of pharmacovigilance (Paris RCPVs) and better describe this rare adverse drug reaction. Forty-five AICN cases were identified between 1985 and 2016. All cases, except one, were reported since 2010. Amoxicillin (AMX) was administered intravenously (65 [interquartile range {IQR}, 43 to 110] mg/kg of body weight/day) in all patients, either for treating infection (n = 15) or as surgical prophylaxis (n = 30). Delay between AMX administration and AICN onset was 1 (IQR, 1 to 3) day; 30, 4, and 11 patients developed KDIGO stage 1, 2, and 3 acute kidney injury, respectively. Delay between AICN onset and kidney function recovery was 4 (IQR, 2 to 6) days. Precipitating factors were identified in only one-third of cases. Twelve patients required intensive care unit admission, and 8 needed renal replacement therapy. Neither chronic kidney disease nor death was observed. We confirmed the recent and dramatic increase of AICN in the Paris RCPVs since 2010. The absence of precipitating factors in the majority of cases and the onset of AICN in apparent routine indications, such as surgical prophylaxis, are alarming and justify a high vigilance from all AMX prescribers.

Development and validation of a pre-hospital "Red Flag" alert for activation of intra-hospital haemorrhage control response in blunt trauma.

BACKGROUND: Haemorrhagic shock is the leading cause of early preventable death in severe trauma. Delayed treatment is a recognized prognostic factor that can be prevented by efficient organization of care. This study aimed to develop and validate Red Flag, a binary alert identifying blunt trauma patients with high risk of severe haemorrhage (SH), to be used by the pre-hospital trauma team in order to trigger an adequate intra-hospital standardized haemorrhage control response: massive transfusion protocol and/or immediate haemostatic procedures. METHODS: A multicentre retrospective study of prospectively collected data from a trauma registry (Traumabase®) was performed. SH was defined as: packed red blood cell (RBC) transfusion in the trauma room, or transfusion ≥ 4 RBC in the first 6 h, or lactate ≥ 5 mmol/L, or immediate haemostatic surgery, or interventional radiology and/or death of haemorrhagic shock. Pre-hospital characteristics were selected using a multiple logistic regression model in a derivation cohort to develop a Red Flag binary alert whose performances were confirmed in a validation cohort. RESULTS: Among the 3675 patients of the derivation cohort, 672 (18%) had SH. The final prediction model included five pre-hospital variables: Shock Index ≥ 1, mean arterial blood pressure ≤ 70 mmHg, point of care haemoglobin ≤ 13 g/dl, unstable pelvis and pre-hospital intubation. The Red Flag alert was triggered by the presence of any combination of at least two criteria. Its predictive performances were sensitivity 75% (72-79%), specificity 79% (77-80%) and area under the receiver operating characteristic curve 0.83 (0.81-0.84) in the derivation cohort, and were not significantly different in the independent validation cohort of 2999 patients. CONCLUSION: The Red Flag alert developed and validated in this study has high performance to accurately predict or exclude SH.

Causes and Characteristics of Death in Intensive Care Units: A Prospective Multicenter Study.

BACKGROUND: Different modes of death are described in selected populations, but few data report the characteristics of death in a general intensive care unit population. This study analyzed the causes and characteristics of death of critically ill patients and compared anticipated death patients to unexpected death counterparts. METHODS: An observational multicenter cohort study was performed in 96 intensive care units. During 1 yr, each intensive care unit was randomized to participate during a 1-month period. Demographic data, characteristics of organ failures (Sequential Organ Failure Assessment subscore greater than or equal to 3), and organ supports were collected on all patients who died in the intensive care unit. Modes of death were defined as anticipated (after withdrawal or withholding of treatment or brain death) or unexpected (despite engagement of full-level care or sudden refractory cardiac arrest). RESULTS: A total of 698 patients were included during the study period. At the time of death, 84% had one or more organ failures (mainly hemodynamic) and 89% required at least one organ support (mainly mechanical ventilation). Deaths were considered unexpected and anticipated in 225 and 473 cases, respectively. Compared to its anticipated counterpart, unexpected death occurred earlier (1 day vs. 5 days; P< 0.001) and had fewer organ failures (1 [1 to 2] vs. 1 [1 to 3]; P< 0.01) and more organ supports (2 [2 to 3] vs. 1 [1 to 2]; P< 0.01). Withdrawal or withholding of treatments accounted for half of the deaths. CONCLUSIONS: In a general intensive care unit population, the majority of patients present with at least one organ failure at the time of death. Anticipated and unexpected deaths represent two different modes of dying and exhibit profiles reflecting the different pathophysiologic underlying mechanisms.

Secondary Insults and Adverse Events During Intrahospital Transport of Severe Traumatic Brain-Injured Patients.

BACKGROUND: Our aim was to assess the occurrence of secondary insults (SIs) or adverse events (AEs) during intrahospital transport (IHT) of severe traumatic brain injury (TBI) patients for head computed tomography (CT) scanning. METHODS: A prospective study based on severe TBI patients admitted from June 2011 through June 2013 in a level I trauma center. Patients received an IHT to perform a control CT scan in the first 3 days following trauma. The occurrence of SIs and AEs was assessed during the IHT for a control CT scan. The frequency of SIs was compared to the periods "before," "during," and "after" IHT. SI was defined by an intracranial pressure (ICP) >30 mmHg, a cerebral perfusion pressure (CPP) <50 mmHg, systolic blood pressure (SBP) <90 mmHg, or saturation pulse O2 (SpO2) <90 % for more than five consecutive minutes. An AE was defined as failures of hardware or ventilator asynchrony requiring therapeutic intervention during transport. In addition, we assessed the therapeutic benefit of a CT scan control. RESULTS: The final analysis included 31 patients and 31 IHTs. The median duration of IHT was 29 min [25;37]. SIs occurred in 16 patients (52 %) during transport, whereas it was observed in 4 patients (13 %) before (p = 0.002) and 4 patients (13 %) after IHT (p = 0.001). Twenty-four AEs occurred during transport of 19 patients (61 %). One patient benefited from hematoma evacuation after implementation of control CT. CONCLUSION: IHT carries significant SIs and AEs in severe TBI patients. To improve a risk/benefit ratio favorable for patients, a program focusing on IHT complications regarding therapeutic impact of control CT scan is needed.

A Brief Period of Hypothermia Induced by Total Liquid Ventilation Decreases End-Organ Damage and Multiorgan Failure Induced by Aortic Cross-Clamping.

BACKGROUND: In animal models, whole-body cooling reduces end-organ injury after cardiac arrest and other hypoperfusion states. The benefits of cooling in humans, however, are uncertain, possibly because detrimental effects of prolonged cooling may offset any potential benefit. Total liquid ventilation (TLV) provides both ultrafast cooling and rewarming. In previous reports, ultrafast cooling with TLV potently reduced neurological injury after experimental cardiac arrest in animals. We hypothesized that a brief period of rapid cooling and rewarming via TLV could also mitigate multiorgan failure (MOF) after ischemia-reperfusion induced by aortic cross-clamping. METHODS: Anesthetized rabbits were submitted to 30 minutes of supraceliac aortic cross-clamping followed by 300 minutes of reperfusion. They were allocated either to a normothermic procedure with conventional ventilation (control group) or to hypothermic TLV (33°C) before, during, and after cross-clamping (pre-clamp, per-clamp, and post-clamp groups, respectively). In all TLV groups, hypothermia was maintained for 75 minutes and switched to a rewarming mode before resumption to conventional mechanical ventilation. End points included cardiovascular, renal, liver, and inflammatory parameters measured 300 minutes after reperfusion. RESULTS: In the normothermic (control) group, ischemia-reperfusion injury produced evidence of MOF including severe vasoplegia, low cardiac output, acute kidney injury, and liver failure. In the TLV group, we observed gradual improvements in cardiac output in post-clamp, per-clamp, and pre-clamp groups versus control (53 ± 8, 64 ± 12, and 90 ± 24 vs 36 ± 23 mL/min/kg after 300 minutes of reperfusion, respectively). Liver biomarker levels were also lower in pre-clamp and per-clamp groups versus control. However, acute kidney injury was prevented in pre-clamp, and to a limited extent in per-clamp groups, but not in the post-clamp group. For instance, creatinine clearance was 4.8 ± 3.1 and 0.5 ± 0.6 mL/kg/min at the end of the follow-up in pre-clamp versus control animals (P = .0004). Histological examinations of the heart, kidney, liver, and jejunum in TLV and control groups also demonstrated reduced injury with TLV. CONCLUSIONS: A brief period of ultrafast cooling with TLV followed by rapid rewarming attenuated biochemical and histological markers of MOF after aortic cross-clamping. Cardiovascular and liver dysfunctions were limited by a brief period of hypothermic TLV, even when started after reperfusion. Conversely, acute kidney injury was limited only when hypothermia was started before reperfusion. Further work is needed to determine the clinical significance of our results and to identify the optimal duration and timing of TLV-induced hypothermia for end-organ protection in hypoperfusion states.

Biofilm-associated infection: the hidden face of cerebrospinal fluid shunt malfunction.

Diagnosis of cerebrospinal fluid (CSF) shunt infection is difficult. Growing evidence links this pattern to biofilm-associated infections (BAI). Biofilm may explain the indolent development of the infection, and the poor efficiency of traditional microbiologic methods. We report the case of a patient admitted for hydrocephalus associated to CSF shunt malfunction. None of the clinical, serum, or CSF laboratory findings were in favor of an infectious process. Only scanning electron microscopy (SEM) revealed the presence of biofilm. Hence, despite a broad CSF shunt infection definition, some infections could remain undiagnosed by the traditional approach. This study is the first to provide some direct evidence for bacterial biofilm-associated CSF shunt infection.

Acute kidney injury following hepatectomy for hepatocellular carcinoma: incidence, risk factors and prognostic value.

BACKGROUND: Acute kidney injury (AKI) following hepatectomy remains understudied in terms of diagnosis, severity, recovery and prognostic value. The aim of this study was to assess the risk factors and prognostic value of AKI on short- and long-term outcomes following hepatectomy for hepatocellular carcinoma (HCC). METHOD: This is a retrospective analysis of a single-center cohort of 457 consecutive patients who underwent hepatectomy for HCC. The KDIGO criteria were used for AKI diagnosis. The incidence, risk factors, and prognostic value of AKI were investigated. RESULTS: AKI occurred in 67 patients (15%). The mortality and major morbidity rates were significantly higher in patients with AKI (37% and 69%) than in those without (6% and 22%; p < 0.001). Renal recovery was complete in 35 (52%), partial in 25 (37%), and absent in 7 (11%) patients. Advanced age, an increased MELD score, major hepatectomy and prolonged duration of operation were identified as independent predictors of AKI. AKI was identified as the strongest independent predictor of postoperative mortality but did not impact survival. CONCLUSION: AKI is a common complication after hepatectomy for HCC. Although its development is associated with poor short-term outcomes, it does not appear to be predictive of impaired long-term survival.

Endovascular balloon occlusion is associated with reduced intraoperative mortality of unstable patients with ruptured abdominal aortic aneurysm but fails to improve other outcomes.

BACKGROUND: Proximal aortic control by endovascular balloon occlusion (EBO) is an alternative to conventional aortic cross-clamping (CAC) in hemodynamically unstable patients presenting with a ruptured abdominal aortic aneurysm (rAAA). The aim of this study was to evaluate the potential clinical benefit of EBO over CAC. METHODS: Data from 72 patients with rAAA treated at our institution from 2001 to 2013 were retrospectively analyzed. All patients were hemodynamically unstable (mean arterial blood pressure at admission <65 mm Hg or associated unconsciousness, cardiac arrest, or emergency endotracheal intubation). Clinical end points of hemodynamic restoration, mortality rate, and major postoperative complications were assessed for CAC (group 1) and EBO (group 2). RESULTS: At admission, 72 patients were unstable. CAC was performed in 40 and EBO in 32. Intraoperative mortality was 43% in group 1 vs 19% in group 2 (P = .031). In group 1, the approach for CAC (thoracotomy [n = 23] vs laparotomy [n = 17]) did not influence intraoperative mortality (43% vs 41%). There was no significant difference in 30-day (75% vs 62%) and in-hospital (77% vs 69%) mortality rates between groups. After EBO, the treatment-open vs endovascular repair-did not influence the intraoperative mortality rate (31% vs 43%; P = .5). Eight surgical complications were secondary to CAC (1 vena cava injury, 3 left renal vein injuries, 1 left renal artery injury, 1 pancreaticoduodenal vein injury, and 2 splenectomies), but no EBO-related complication was noted (P = .04). Differences in colon ischemia (15% vs 28%) and renal failure (12% vs 9%) were not statistically significant. Abdominal compartment syndrome occurred in four patients in group 2 and in no patients in group 1. CONCLUSIONS: Compared with CAC, EBO is a feasible and valuable strategy and is associated with reduced intraoperative mortality of unstable rAAA patients, but not in-hospital mortality, in this retrospective study.

Clinical, biological, and microbiological pattern associated with ventriculostomy-related infection: a retrospective longitudinal study.

BACKGROUND: Our aim was to describe the pattern of ventriculostomy-related infection (VRI) development using a dynamic approach. STUDY DESIGN: Retrospective longitudinal study. METHODS: We analyzed the files of 449 neurosurgical patients who underwent placement of external ventricular drain (EVD). During the study period, CSF sampling was performed on a daily base setting. VRI was defined as a positive CSF culture resulting in antibiotic treatment. For VRI patients, we arbitrary defined day 0 (D0) as the day antibiotic treatment was started. In these patients, we compared dynamic changes in clinical and biological parameters at four pre-determined time points: (D-4, D-3, D-2, D-1) with those of D0. For all CSF-positive cultures, we compared CSF biochemical markers' evolution pattern between VRI patients and the others, considered as a control cohort. RESULTS: Thirty-two suffered from VRI. Peripheral white blood cell count did not differ between D-4-D0. Median body temperature, CSF cell count, median Glasgow Coma Scale, CSF protein, and glucose concentrations were significantly different between D-4, D-3, D-2, and D0. At D0, 100 % of CSF samples yielded organisms in culture. The physician caring for the patient decided to treat VRI based upon positive CSF culture in only 28 % (9/32) of cases. In the control cohort, CSF markers' profile trends to normalize, while it worsens in the VRI patients. CONCLUSIONS: We showed that clinical symptoms and biological abnormalities of VRI evolved over time. Our data suggest that VRI decision to treat relies upon a bundle of evidence, including dynamic changes in CSF laboratory exams combined with microbiological analysis.

Predictors of functional outcome after intraoperative cardiac arrest.

BACKGROUND: Few outcome data are available about intraoperative cardiac arrest (IOCA). The authors studied 90-day functional outcomes and their determinants in patients admitted to the intensive care unit after IOCA. METHODS: Patients admitted to 11 intensive care units in a period of 2000-2013 were studied retrospectively. The main outcome measure was a day-90 Cerebral Performance Category score of 1 or 2. RESULTS: Of the 140 patients (61 women and 79 men; median age, 60 yr [interquartile range, 46 to 70]), 131 patients (93.6%) had general anesthesia, 80 patients (57.1%) had emergent surgery, and 73 patients (52.1%) had IOCA during surgery. First recorded rhythms were asystole in 73 patients (52.1%), pulseless electrical activity in 44 patients (31.4%), and ventricular fibrillation/ventricular tachycardia in 23 patients (16.4%). Median times from collapse to cardiopulmonary resuscitation and return of spontaneous circulation were 0 min (0 to 0) and 10 min (5 to 20), respectively. Postcardiac arrest shock was identified in 114 patients (81.4%). Main causes of IOCA were preoperative complications (n = 46, 32.9%), complications of anesthesia (n = 39, 27.9%), and complications of surgical procedures (n = 36, 25.7%). On day 90, 63 patients (45.3%) were alive with Cerebral Performance Category score 1/2. Independent predictors of day-90 Cerebral Performance Category score 1/2 were day-1 Logistic Organ Dysfunction score (odds ratio, 0.78 per point; 95% CI, 0.71 to 0.87; P = 0.0001), ventricular fibrillation/tachycardia as first recorded rhythm (odds ratio, 4.78; 95% CI, 1.38 to 16.53; P = 0.013), and no epinephrine therapy during postcardiac arrest syndrome (odds ratio, 3.14; 95% CI, 1.29 to 7.65; P = 0.012). CONCLUSIONS: By day 90, 45% of IOCA survivors had good functional outcomes. The main outcome predictors were directly related to IOCA occurrence and postcardiac arrest syndrome; they suggest that the intensive care unit management of postcardiac arrest syndrome may be amenable to improvement.

Hydrocortisone plus fludrocortisone for community acquired pneumonia-related septic shock: a subgroup analysis of the APROCCHSS phase 3 randomised trial.

BACKGROUND: Glucocorticoids probably improve outcomes in patients hospitalised for community acquired pneumonia (CAP). In this a priori planned exploratory subgroup analysis of the phase 3 randomised controlled Activated Protein C and Corticosteroids for Human Septic Shock (APROCCHSS) trial, we aimed to investigate responses to hydrocortisone plus fludrocortisone between CAP and non-CAP related septic shock. METHODS: APROCCHSS was a randomised controlled trial that investigated the effects of hydrocortisone plus fludrocortisone, drotrecogin-alfa (activated), or both on mortality in septic shock in a two-by-two factorial design; after drotrecogin-alfa was withdrawn on October 2011, from the market, the trial continued on two parallel groups. It was conducted in 34 centres in France. In this subgroup study, patients with CAP were a preselected subgroup for an exploratory secondary analysis of the APROCCHSS trial of hydrocortisone plus fludrocortisone in septic shock. Adults with septic shock were randomised 1:1 to receive, in a double-blind manner, a 7-day treatment with daily administration of intravenous hydrocortisone 50 mg bolus every 6h and a tablet of 50 µg of fludrocortisone via the nasogastric tube, or their placebos. The primary outcome was 90-day all-cause mortality. Secondary outcomes included all-cause mortality at intensive care unit (ICU) and hospital discharge, 28-day and 180-day mortality, the number of days alive and free of vasopressors, mechanical ventilation, or organ failure, and ICU and hospital free-days to 90-days. Analysis was done in the intention-to-treat population. The trial was registered at ClinicalTrials.gov (NCT00625209). FINDINGS: Of 1241 patients included in the APROCCHSS trial, CAP could not be ruled in or out in 31 patients, 562 had a diagnosis of CAP (279 in the placebo group and 283 in the corticosteroid group), and 648 patients did not have CAP (329 in the placebo group and 319 in the corticosteroid group). In patients with CAP, there were 109 (39%) deaths of 283 patients at day 90 with hydrocortisone plus fludrocortisone and 143 (51%) of 279 patients receiving placebo (odds ratio [OR] 0·60, 95% CI 0·43-0·83). In patients without CAP, there were 148 (46%) deaths of 319 patients at day 90 in the hydrocortisone and fludrocortisone group and 157 (48%) of 329 patients in the placebo group (OR 0·95, 95% CI 0·70-1·29). There was significant heterogeneity in corticosteroid effects on 90-day mortality across subgroups with CAP and without CAP (p=0·046 for both multiplicative and additive interaction tests; moderate credibility). Of 1241 patients included in the APROCCHSS trial, 648 (52%) had ARDS (328 in the placebo group and 320 in the corticosteroid group). There were 155 (48%) deaths of 320 patients at day 90 in the corticosteroid group and 186 (57%) of 328 patients in the placebo group. The OR for death at day 90 was 0·72 (95% CI 0·53-0·98) in patients with ARDS and 0·85 (0·61-1·20) in patients without ARDS (p=0·45 for multiplicative interaction and p=0·42 for additive interaction). The OR for observing at least one serious adverse event (corticosteroid group vs placebo) within 180 days post randomisation was 0·64 (95% CI 0·46-0·89) in the CAP subgroup and 1·02 (0·75-1·39) in the non-CAP subgroup (p=0·044 for multiplicative interaction and p=0·042 for additive interaction). INTERPRETATION: In a pre-specified subgroup analysis of the APROCCHSS trial of patients with CAP and septic shock, hydrocortisone plus fludrocortisone reduced mortality as compared with placebo. Although a large proportion of patients with CAP also met criteria for ARDS, the subgroup analysis was underpowered to fully discriminate between ARDS and CAP modifying effects on mortality reduction with corticosteroids. There was no evidence of a significant treatment effect of corticosteroids in the non-CAP subgroup. FUNDING: Programme Hospitalier de Recherche Clinique of the French Ministry of Health, by Programme d'Investissements d'Avenir, France 2030, and IAHU-ANR-0004.

COVID-19, air quality and space monitoring.

Due to the worldwide spread of the coronavirus disease 2019 (COVID-19), human mobility and economic activity have slowed down considerably since early 2020. A relatively high number of those infected develop serious pneumonia leading to progressive respiratory failure, system disease and often death. Apart from close human-to-human contact, the acceleration and global diffusion of this pandemic has been shown to be associated with changes in atmospheric chemistry and air pollution by microscopic particulate matter (PM). Breathing air with high concentrations of nitrogen dioxide and PM can result in over-expression of the angiotensin converting enzyme-2 (ACE-2) leading to stress of organs, such as heart and kidneys. Satellite monitoring can play a crucial role in spatio-temporal surveillance of the disease by producing data on pollution as proxy for industrial activity, transport and traffic circulation. Real-time monitoring of COVID-19 in air and chemical pollution of the atmospheric boundary layer available from Earth-observing satellites commuting with Health Information Systems (HIS) would be useful for decision makers involved with public health.

Metabolomic approach by 1H NMR spectroscopy of serum for the assessment of chronic liver failure in patients with cirrhosis.

Assessment of chronic liver failure (CLF) in cirrhotic patients is needed to make therapeutic decisions. A biological score is usually performed, using the Model for End-Stage Liver Disease (MELD), to evaluate CLF. Nevertheless, MELD does not take into account metabolic perturbations produced by liver-function impairment. In contrast, metabolomics can investigate many metabolic perturbations within biological systems. The purpose of this study was to assess whether metabolomic profiles of serum, obtained by proton NMR spectroscopy from cirrhotic patients, are affected by the severity of CLF. An orthogonal projection to latent-structure analysis was performed to compare MELD scores and NMR spectra of 124 patients with cirrhosis. The statistical model obtained showed a good explained variance (R(2)X = 0.87 and R(2)Y = 0.86) and a good predictability (Q(2)Y = 0.64). Metabolomic profiles showed significant differences regarding various metabolites depending of severity of CLF: levels of high-density lipoprotein and phosphocholine resonances were significantly higher in patients with mild CLF compared to severe CLF. Other metabolites such as lactate, pyruvate, glucose, amino acids, and creatinine were significantly higher in patients with severe CLF than mild CLF. Our conclusion is that metabolomic NMR analysis provides new insights into metabolic processes related to the severity of hepatic function impairment in cirrhosis.

Unanticipated difficult airway management in the prehospital emergency setting: prospective validation of an algorithm.

BACKGROUND: Difficult intubation management algorithms have proven efficacy in operating rooms but have rarely been assessed in a prehospital emergency setting. We undertook a prospective evaluation of a simple prehospital difficult intubation algorithm. METHODS: All of our prehospital emergency physicians and nurse anesthetists were asked to adhere to a simple algorithm in all cases of impossible laryngoscope-assisted tracheal intubation. They received a short refresher course and training in the use of the gum elastic bougie (GEB) and the intubating laryngeal mask airway (ILMA), which were techniques to be used as a first and a second step, respectively. In cases of difficult ventilation with arterial desaturation, IMLA was to be used first. Cricothyroidotomy was the ultimate rescue technique when ventilation through ILMA failed. Patient characteristics, adherence to the algorithm, management efficacy, and early complications were recorded (August 2005-December 2009). RESULTS: An alternative technique to secure the airway was needed in 160 of 2,674 (6%) patients undergoing intubation. Three instances of nonadherence to the algorithm were recorded. GEB was used first in 152 patients and was successful in 115. ILMA was used first in 8 patients and second in the 37 GEB-assisted intubation failures. Forty-five patients were successfully mask-ventilated, and 42 were blindly intubated before reaching the hospital. Cricothyroidotomy was used successfully in a patient with severe upper airway obstruction as a result of pharyngeal neoplasia. Early intubation-related complications occurred in 52% difficult cases. CONCLUSION: Adherence to a simple algorithm using GEB, ILMA, and cricothyroidotomy solved all difficult intubation cases occurring in a prehospital emergency setting.