Anaphylaxis is a systemic acute hypersensitivity reaction that is considered to depend on allergen-specific immunoglobulin E (IgE) antibodies and histamine release by mast cells and basophils. Nevertheless, allergen-specific IgG antibodies have been proposed to contribute when the allergen is an abundant circulating large molecule, e.g., after infusions of therapeutic antibodies or dextran. Data from animal models demonstrate a pathway involving platelet-activating factor (PAF) release by monocytes/macrophages and neutrophils activated via their Fc gamma receptors (FcγRs). We hypothesized that such a pathway may also apply to small drugs and could be responsible for non–IgE-mediated anaphylaxis and influence anaphylaxis severity in humans. We prospectively conducted a multicentric study of 86 patients with suspected anaphylaxis to neuromuscular-blocking agents (NMBAs) during general anesthesia and 86 matched controls. We found that concentrations of anti-NMBA IgG and markers of FcγR activation, PAF release, and neutrophil activation correlated with anaphylaxis severity. Neutrophils underwent degranulation and NETosis early after anaphylaxis onset, and plasma-purified anti-NMBA IgG triggered neutrophil activation ex vivo in the presence of NMBA. Neutrophil activation could also be observed in patients lacking evidence of classical IgE-dependent anaphylaxis. This study supports the existence of an IgG-neutrophil pathway in human NMBA-induced anaphylaxis, which may aggravate anaphylaxis in combination with the IgE pathway or underlie anaphylaxis in the absence of specific IgE. These results reconcile clinical and experimental data on the role of antibody classes in anaphylaxis and could inform diagnostic approaches to NMBA-induced acute hypersensitivity reactions.

Knowledge of the pathophysiological mechanisms of acute kidney injury emphasizes the importance of the role of the microcirculation in its development. Preventive and therapeutic approach should be based on restoring the homeostasis between nitric oxide, reactive oxygen species and renal oxygenation.

IntroductionSeptic shock is one of the most frequent causes of admission to the intensive care unit (ICU) and is associated with a poor prognosis. Early and late death in septic shock should be distinguished because they may involve different underlying mechanisms. In various conditions, the neutrophil-to-lymphocyte count ratio (NLCR) has been described as an easily measurable parameter to express injury severity. In the present study, we investigated whether the timing of death was related to a particular NLCR.MethodsWe conducted a prospective, single-center, observational study that included consecutive septic shock patients. Severity scores, early (before day 5) or late (on or after day 5 of septic shock onset) ICU mortality, and daily leukocyte counts were collected during the ICU stay. We assessed the association between leukocyte counts at admission and their evolution during the first 5 days with early or late death. The association between patient characteristics (including cell counts) and prognosis was estimated using Cox proportional cause-specific hazards models.ResultsThe study included 130 patients who were diagnosed with abdominal (n = 99) or extra-abdominal (n = 31) septic shock. The median (interquartile range) NLCR was 12.5 (6.5–21.2) in survivors and 6.2 (3.7–12.6) in nonsurvivors (p = 0.001). The NLCR at admission was significantly lower in patients who died before day 5 than in survivors (5 [3.5–11.6] versus 12.5 [6.5–21.2], respectively; p = 0.01). From day 1 to day 5, an increased NLCR related to an increase in neutrophil count and a decrease in lymphocyte count was associated with late death (+34.8 % [−8.2 to 305.4] versus −20 % [−57.4 to 45.9]; p = 0.003). Those results were present in patients with abdominal origin sepsis as well as in those with extra-abdominal sepsis, who were analyzed separately.ConclusionsIn the present study, a reversed NLCR evolution was observed according to the timing of death. Septic shock patients at risk of early death had a low NLCR at admission, although late death was associated with an increased NLCR during the first 5 days.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-015-1144-x) contains supplementary material, which is available to authorized users.

SARS-CoV-2 has caused a global pandemic unprecedented in size, spread, severity, and mortality. The influx of patients with severe or life-threatening disease means that in some cases, the available medical resources are not sufficient to meet the needs of all patients. Hence, healthcare providers may be forced to make difficult choices about which patients should be referred to the ICU. This document is intended to provide conceptual support to all healthcare teams currently engaged in the frontline management of the COVID-19 pandemic. It aims to assist physicians in the decision-making process for ICU admission and to help them provide uninterrupted and highquality care.

BackgroundThe choice of empirical antimicrobial therapy for pneumonia in intensive care unit (ICU) is a challenge, since pneumonia is often related to multidrug-resistant pathogens, particularly extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E). To prevent the overuse of broad-spectrum antimicrobial therapy, the main objective of this study was to test the performance of digestive colonization surveillance as a predictor of ESBL-E presence or absence in respiratory samples performed in ICU and to evaluate the impact of time sampling (≤5 days or >5 days) on such prediction. Design: Multicentric retrospective observational study, including every patient with a respiratory tract specimen positive culture and a previous rectal ESBL-E screening performed within 7 days before the respiratory sample, between January 2012 and December 2014. Results were analyzed in two groups: respiratory samples obtained during the first 5 days of ICU stay (early group) and respiratory samples obtained after 5 days (late group). Interventions: none.ResultsAmong 2498 respiratory tract samples analyzed corresponding to 1503 patients, 1557 (62.3%) were performed early (≤5 days) and 941 (37.7%) later (>5 days). Positivity rates for ESBL-E were 15.0 and 36.8% for rectal swabs in the early and late groups, respectively. Sensitivity, specificity, positive (PPV) and negative (NPV) predictive values and likelihood ratios were calculated for ESBL-E digestive colonization as a predictor of ESBL-E presence in respiratory samples. PPVs of ESBL-E digestive colonization were 14.5% (95% CI [12.8; 16.3]) and 34.4% (95% CI [31.4; 37.4]), for the early and late groups, respectively, whereas NPVs were 99.2% (95% CI [98.7; 99.6]) and 93.4% (95% CI [91.9; 95.0]), respectively.ConclusionsSystematic surveillance of ESBL-E digestive colonization may be useful to limit the use of carbapenems when pneumonia is suspected in ICU. When rectal swabs are negative, the risk of having ESBL-E in respiratory samples is very low even after 5 days of ICU stay.Electronic supplementary materialThe online version of this article (doi:10.1186/s13613-017-0237-x) contains supplementary material, which is available to authorized users.

Despite our increasing ability to support vital organs and resuscitate patients, the morbidity and mortality of acute kidney injury (AKI) remain high in the intensive care unit (ICU). The ability to predict the occurrence of AKI is crucial for the development of preventive strategies. Early diagnosis of AKI requires markers that are sensitive and easily applicable in clinical practice. The use of Doppler ultrasonography to assess renal perfusion is increasing in many kidney diseases and in the ICU. The Doppler-based renal resistive index, which is a simple, rapid, noninvasive, and repeatable marker, could be a promising tool to prematurely detect the patients most at risk of developing AKI in the ICU and to distinguish transient from persistent AKI. Moreover, the resistive index could also be useful to adjust preventive or therapeutic modalities for the kidney perfusion at the bedside. The recent progress in ultrasound with contrast-enhanced ultrasound gives the opportunity to assess not only the kidney macrocirculation but also the kidney microcirculation in the ICU.

OBJECTIVES: Although clinical presentation of coronavirus disease 2019 has been extensively described, immune response to severe acute respiratory syndrome coronavirus 2 remains yet not fully understood. Similarities with bacterial sepsis were observed; however, few studies specifically addressed differences of immune response between both conditions. Here, we report a longitudinal analysis of the immune response in coronavirus disease 2019 patients, its correlation with outcome, and comparison between severe coronavirus disease 2019 patients and septic patients. DESIGN: Longitudinal, retrospective observational study. SETTING: Tertiary-care hospital during the first 2020 coronavirus disease 2019 outbreak in France. PATIENTS: All successive patients with confirmed severe acute respiratory syndrome coronavirus 2 infection admitted to the emergency department, medical ward, and ICU with at least one available immunophenotyping performed during hospital stay. MEASUREMENTS AND MAIN RESULTS: Between March and April 2020, 247 patients with coronavirus disease 2019 were included and compared with a historical cohort of 108 severe septic patients. Nonsevere coronavirus disease 2019 patients (n = 153) presented normal or slightly altered immune profiles. Severe coronavirus disease 2019 (n = 94) immune profile differed from sepsis. Coronavirus disease 2019 exhibited profound and prolonged lymphopenia (mostly on CD3, CD4, CD8, and NK cells), neutrophilia, and human leukocyte antigen D receptor expression on CD14+ monocytes down-regulation. Surprisingly, coronavirus disease 2019 patients presented a unique profile of B cells expansion, basophilia, and eosinophilia. Lymphopenia, human leukocyte antigen D receptor expression on CD14+ monocytes down-regulation, and neutrophilia were associated with a worsened outcome, whereas basophilia and eosinophilia were associated with survival. Circulating immune cell kinetics differed between severe coronavirus disease 2019 and sepsis, lack of correction of immune alterations in coronavirus disease 2019 patients during the first 2 weeks of ICU admission was associated with death and nosocomial infections. CONCLUSIONS: Circulating immune cells profile differs between mild and severe coronavirus disease 2019 patients. Severe coronavirus disease 2019 is associated with a unique immune profile as compared with sepsis. Several immune features are associated with outcome. Thus, immune monitoring of coronavirus disease 2019 might be of help for patient management.

Inappropriate antibiotic therapy in ventilator-associated pneumonia (VAP) is associated with increased mortality. Using broad-spectrum antibiotics for 48 h until the results of conventional cultures and antimicrobial susceptibility testing (AST) are available, may promote the emergence of drug-resistant bacteria. Performing AST directly on clinical respiratory samples would hasten the process by at least 24 h. Here, we analysed the diagnostic performance of a rapid method combining mass spectrometry and direct AST (DAST), and compared it with the conventional method (mass spectrometry with conventional AST (CAST)). Additionally, we assessed its potential impact on antimicrobial use in patients. Over a period of 18 months, the two methods were performed on 85 bronchoalveolar lavages obtained from intensive care unit patients with suspected VAP, and in which Gram-negative bacilli were observed on direct examination. Only the CAST results were reported to the clinicians. DAST produced useable results in 85.9% of the patients. The sensitivity and negative predictive values of DAST were 100% for all antibiotics tested, except gentamicin (97.1%, (95% CI 93.3-101) and 97.4% (93.7-101), respectively) and amikacin (88.9% (81.7-96.1) and 96.4% (92.1-100.7), respectively), compared with CAST. Specificity and positive predictive values ranged from 82.9 (74.2-91.5) to 100%, and from 86.4 (78.5-94.2) to 100%, respectively. If the DAST results had been reported to the clinicians, treatment could have been optimized 24 h earlier in 35/85 (41.2%) patients, with 17 carbapenem patient-days saved. Overall, routine use of the DAST method could help optimize earlier antibiotic treatment in patients with suspected VAP.