Characterization of Blood Immune Cells in Patients With Decompensated Cirrhosis Including ACLF

Background and Aims: Patients with cirrhosis and acute-on-chronic liver failure (ACLF) have immunosuppression, indicated by an increase in circulating immune-deficient monocytes. The aim of this study was to investigate simultaneously the major blood-immune cell subsets in these patients. Material and Methods: Blood taken from 67 patients with decompensated cirrhosis (including 35 critically ill with ACLF in the intensive care unit), and 12 healthy subjects, was assigned to either measurements of clinical blood counts and microarray (genomewide) analysis of RNA expression in whole-blood; microarray (genomewide) analysis of RNA expression in blood neutrophils; or assessment of neutrophil antimicrobial functions. Results: Several features were found in patients with ACLF and not in those without ACLF. Indeed, clinical blood count measurements showed that patients with ACLF were characterized by leukocytosis, neutrophilia, and lymphopenia. Using the CIBERSORT method to deconvolute the whole-blood RNA-expression data, revealed that the hallmark of ACLF was the association of neutrophilia with increased proportions of macrophages M0-like monocytes and decreased proportions of memory lymphocytes (of B-cell, CD4 T-cell lineages), CD8 T cells and natural killer cells. Microarray analysis of neutrophil RNA expression revealed that neutrophils from patients with ACLF had a unique phenotype including induction of glycolysis and granule genes, and downregulation of cell-migration and cell-cycle genes. Moreover, neutrophils from these patients had defective production of the antimicrobial superoxide anion. Conclusions: Genomic analysis revealed that, among patients with decompensated cirrhosis, those with ACLF were characterized by dysregulation of blood immune cells, including increases in neutrophils (that had a unique phenotype) and macrophages M0-like monocytes, and depletion of several lymphocyte subsets (including memory lymphocytes). All these lymphocyte alterations, along with defective neutrophil superoxide anion production, may contribute to immunosuppression in ACLF, suggesting targets for future therapies

Learning from terrorist mass casualty incidents: a global survey

Background: Reports published directly after terrorist mass casualty incidents frequently fail to capture difficulties that may have been encountered. An anonymised consensus-based platform may enable discussion and collaboration on the challenges faced. Our aim was to identify where to focus improvement for future responses. Methods: We conducted a mixed methods study by email of clinicians\u27 experiences of leading during terrorist mass casualty incidents. An initial survey identified features that worked well, or failed to, during terrorist mass casualty incidents plus ongoing challenges and changes that were implemented as a result. A follow-up, quantitative survey measured agreement between responses within each of the themes using a Likert scale. Results: Thirty-three participants responded from 22 hospitals that had received casualties from a terrorist incident, representing 17 cities in low-middle, middle and high income countries. The first survey identified themes of sufficient (sometimes abundant) human resource, although coordination of staff was a challenge. Difficulties highlighted were communication, security, and management of blast injuries. The most frequently implemented changes were education on specific injuries, revising future plans and preparatory exercises. Persisting challenges were lack of time allocated to training and psychological well-being. The follow-up survey recorded highest agreement amongst correspondents on the need for re-triage at hospital (90% agreement), coordination roles (85% agreement), flexibility (100% agreement), and large-scale exercises (95% agreement). Conclusion: This survey collates international experience gained from clinicians managing terrorist mass casualty incidents. The organisation of human response, rather than consumption of physical supplies, emerged as the main finding

Multiple trauma in pregnant women: injury assessment, fetal radiation exposure and mortality. A multicentre observational study

Abstract Background Fetal radiation exposure in pregnant women with trauma is a concern. The purpose of this study was to evaluate fetal radiation exposure with regard to the type of injury assessment performed. Methods It is a multicentre observational study. The cohort study included all pregnant women suspected of severe traumatic injury in the participating centres of a national trauma research network. The primary outcome was the cumulative radiation dose (mGy) received by the fetus with respect to the type of injury assessment initiated by the physician in charge of the pregnant patient. Secondary outcomes were maternal and fetal morbi-mortality, the incidence of haemorrhagic shock and the physicians’ imaging assessment with consideration of their medical specialty. Results Fifty-four pregnant women were admitted for potential major trauma between September 2011 and December 2019 in the 21 participating centres. The median gestational age was 22 weeks [12–30]. 78% of women (n = 42) underwent WBCT. The remaining patients underwent radiographs, ultrasound or selective CT scans based on clinical examination. The median fetal radiation doses were 38 mGy [23–63] and 0 mGy [0–1]. Maternal mortality (6%) was lower than fetal mortality (17%). Two women (out of 3 maternal deaths) and 7 fetuses (out of 9 fetal deaths) died within the first 24 h following trauma. Conclusions Immediate WBCT for initial injury assessment in pregnant women with trauma was associated with a fetal radiation dose below the 100 mGy threshold. Among the selected population with either a stable status with a moderate and nonthreatening injury pattern or isolated penetrating trauma, a selective strategy seemed safe in experienced centres

Effect of Fibrinogen concentrate administration on early mortality in traumatic hemorrhagic shock

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Early hyperoxemia is associated with lower adjusted mortality after severe trauma: results from a French registry

International audienceBackground: Hyperoxemia has been associated with increased mortality in critically ill patients, but little is known about its effect in trauma patients. The objective of this study was to assess the association between early hyperoxemia and in-hospital mortality after severe trauma. We hypothesized that a PaO2 ≥ 150 mmHg on admission was associated with increased in-hospital mortality.Methods: Using data issued from a multicenter prospective trauma registry in France, we included trauma patients managed by the emergency medical services between May 2016 and March 2019 and admitted to a level I trauma center. Early hyperoxemia was defined as an arterial oxygen tension (PaO2) above 150 mmHg measured on hospital admission. In-hospital mortality was compared between normoxemic (150 > PaO2 ≥ 60 mmHg) and hyperoxemic patients using a propensity-score model with predetermined variables (gender, age, prehospital heart rate and systolic blood pressure, temperature, hemoglobin and arterial lactate, use of mechanical ventilation, presence of traumatic brain injury (TBI), initial Glasgow Coma Scale score, Injury Severity Score (ISS), American Society of Anesthesiologists physical health class > I, and presence of hemorrhagic shock).Results: A total of 5912 patients were analyzed. The median age was 39 [26-55] years and 78% were male. More than half (53%) of the patients had an ISS above 15, and 32% had traumatic brain injury. On univariate analysis, the in-hospital mortality was higher in hyperoxemic patients compared to normoxemic patients (12% versus 9%, p < 0.0001). However, after propensity score matching, we found a significantly lower in-hospital mortality in hyperoxemic patients compared to normoxemic patients (OR 0.59 [0.50-0.70], p < 0.0001).Conclusion: In this large observational study, early hyperoxemia in trauma patients was associated with reduced adjusted in-hospital mortality. This result contrasts the unadjusted in-hospital mortality as well as numerous other findings reported in acutely and critically ill patients. The study calls for a randomized clinical trial to further investigate this association

Thoracic Epidural Analgesia and Mortality in Acute Pancreatitis A Multicenter Propensity Analysis

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Risk factors and outcomes for airway failure versus non-airway failure in the intensive care unit: a multicenter observational study of 1514 extubation procedures

Abstract Background Patients liberated from invasive mechanical ventilation are at risk of extubation failure, including inability to breathe without a tracheal tube (airway failure) or without mechanical ventilation (non-airway failure). We sought to identify respective risk factors for airway failure and non-airway failure following extubation. Methods The primary endpoint of this prospective, observational, multicenter study in 26 intensive care units was extubation failure, defined as need for reintubation within 48 h following extubation. A multinomial logistic regression model was used to identify risk factors for airway failure and non-airway failure. Results Between 1 December 2013 and 1 May 2015, 1514 patients undergoing extubation were enrolled. The extubation-failure rate was 10.4% (157/1514), including 70/157 (45%) airway failures, 78/157 (50%) non-airway failures, and 9/157 (5%) mixed airway and non-airway failures. By multivariable analysis, risk factors for extubation failure were either common to airway failure and non-airway failure: intubation for coma (OR 4.979 (2.797–8.864), P  8 days (OR 1.956 (1.087–3.518), P = 0.025), copious secretions (OR 4.066 (2.268–7.292), P < 0.0001) were specific to airway failure, whereas non-obese status (OR 2.153 (1.052–4.408), P = 0.036) and sequential organ failure assessment (SOFA) score ≥ 8 (OR 1.848 (1.100–3.105), P = 0.02) were specific to non-airway failure. Both airway failure and non-airway failure were associated with ICU mortality (20% and 22%, respectively, as compared to 6% in patients with extubation success, P < 0.0001). Conclusions Specific risk factors have been identified, allowing us to distinguish between risk of airway failure and non-airway failure. The two conditions will be managed differently, both for prevention and curative strategies. Trial registration ClinicalTrials.gov, NCT 02450669. Registered on 21 May 2015

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

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