Diaphragm function in patients with sepsis and septic shock: A longitudinal ultrasound study.

BACKGROUND: Previous literature on the determinants of diaphragm dysfunction in septic patients is limited. The goal of this study is to assess diaphragm dysfunction in terms of its prevalence and its potential associated factors in septic intensive care unit (ICU) patients. METHODS: This prospective and observational study was conducted between June 2015 and July 2019. Ultrasound measures of diaphragm thickness were performed daily on septic patients. The primary outcome was the prevalence of diaphragm dysfunction at baseline and during the ICU stay. The secondary outcome was the diaphragm thickness. Possible associated factors were prospectively recorded. RESULTS: Fifty patients were enrolled in the study. The prevalence of diaphragm dysfunction was 58%. No diaphragm atrophy was found during the ICU stay. Diaphragm dysfunction was associated with the alteration of consciousness, intra-abdominal sepsis, hypnotics and opioids, and mechanical ventilation. Administration of hypnotics, opioids, and steroids was associated with a decreased diaphragm thickening fraction. Diaphragm dysfunction had no impact on patient outcomes. CONCLUSIONS: Our data reveal a high prevalence of diaphragm dysfunction in septic patients at the onset of sepsis. Administration of hypnotics, opioids, and steroids was associated with the alteration of diaphragm function as well as intra-abdominal sepsis.

T cell dysregulation in inflammatory diseases in ICU.

Severe inflammatory diseases, including sepsis, are characterized by an impaired host adaptive and innate immunity which results in immunosuppression, responsible for secondary infections and increased morbidity and mortality in critically ill patients. T cells are major actors of the immune system. During post-aggressive immunosuppression, lymphopenia, reduction of innate T cells, changes in T helper cell polarization and regulatory T cell increase are observed. The main mechanisms involved in T cell dysregulation are T cell apoptosis, autophagy deficiency, T cell anergy, T cell exhaustion and T cell metabolic reprogramming. In this review, we describe the alterations of T cell regulation, their mechanisms, and their association with clinical outcomes in severe inflammatory diseases, foremost of which is the sepsis.

Endothelial Cells Activated by Extracellular Histones Promote Foxp3+ Suppressive Treg Cells In Vitro.

Histones are widely recognized as pro-inflammatory mediators upon their release from the nucleus into the extracellular space. However, their impact on endothelial cell immunogenicity is unknown. Endothelial cells, Human Microvascular Endothelial cells 1 (HMEC1), have been exposed to recombinant histones in order to study their effect on the endothelial phenotype. We then studied the differentiation of CD4+-T lymphocytes subpopulations after three days of interaction with endothelial cells in vitro and observed that histone-treated endothelial cells differentiate a suppressive FoxP3+ T regulator subpopulation that expressed Human Leucocyte Antigen DR (HLA-DR) and Cytotoxic T-Lymphocyte-Associated protein 4 (CTLA4). Toll-Like Receptor 4 (TLR4) inhibition significantly decreased the expansion of these Treg cells. Moreover, blockade of Interleukin (IL)-6 and Intercellular Adhesion Molecule (ICAM)-1 in cocultures significantly decreased the expansion of Tregs, suggesting an IL-6 and ICAM-1 dependent pathway. Thus, beyond their inflammatory effects, extracellular histones may induce an increase of immunosuppressive Treg population via their action on endothelial cells. Further studies are needed to evaluate the impact on immunosuppression of an increase of peripheral suppressive Treg via endothelial cell activation by histones in vivo.

Diagnostic accuracy of diaphragm ultrasound to predict weaning outcome: A systematic review and meta-analysis.

BACKGROUND: The accuracy of diaphragm ultrasound for predicting weaning outcome is still debated, despite the publication of numerous studies evaluating this issue. OBJECTIVE: The aim of this systematic review and meta-analysis was to assess the diagnostic accuracy of diaphragm ultrasound for predicting weaning failure in critically ill patients. DESIGN AND DATA SOURCES: MEDLINE, Science direct, Cochrane Library, EMBASE and CENTRAL were searched. Two investigators independently selected studies that met the inclusion criteria, and three extracted data and performed a bias analysis using the Quality Assessment of Diagnostic Accuracy Studies-2 instrument. A bivariate model was used to estimate the pooled results for sensitivity, specificity and diagnostic odds ratio. Sources of heterogeneity were explored, and subgroup analyses were performed. RESULTS: Twenty-eight studies were included in the systematic review, from which 16 studies (816 patients in total) were included in the meta-analysis. The pooled sensitivity, specificity and area under the summary receiver operator characteristic curve were 0.70 (95% CI 0.57-0.80), 0.84 (95% CI 0.73-0.91), and 0.82 (95% Cl 0.78-0.85) for diaphragm thickening fraction, respectively, and 0.71 (95% CI 0.61-0.79), 0.80 (95% CI 0.73-0.86), and 0.82 (95% Cl 0.79-0.86) for diaphragm excursion, respectively. There was substantial heterogeneity among the studies. Meta-regression highlighted significant effects of prevalence of extubation failure, cut-off and risk of bias in flow and timing of the study on diaphragm ultrasound accuracy. By excluding outlier and influential studies, sensitivity was lower and specificity higher for diaphragm thickening fraction. CONCLUSION: The specificity of diaphragm ultrasound for predicting the risk of extubation failure in critically ill patients was moderate-to-high. However, sensitivity was low because weaning is also affected by non-diaphragm-related factors. Further research in subgroups of critically ill patients applying a homogeneous definition of weaning and uniformly conducted measure is needed to assess the accuracy of diaphragm ultrasound. CLINICAL TRIAL REGISTRATION: Registered on http://www.crd.york.ac.uk/PROSPERO as CRD42017058028. Tweetable abstract: Diaphragm ultrasound predicts extubation failure with high specificity. Absence of diaphragm dysfunction does not imply no risk of extubation failure.