Host adaptive immunity deficiency in severe pandemic influenza

INTRODUCTION: Pandemic A/H1N1/2009 influenza causes severe lower respiratory complications in rare cases. The association between host immune responses and clinical outcome in severe cases is unknown. METHODS: We utilized gene expression, cytokine profiles and generation of antibody responses following hospitalization in 19 critically ill patients with primary pandemic A/H1N1/2009 influenza pneumonia for identifying host immune responses associated with clinical outcome. Ingenuity pathway analysis 8.5 (IPA) (Ingenuity Systems, Redwood City, CA) was used to select, annotate and visualize genes by function and pathway (gene ontology). IPA analysis identified those canonical pathways differentially expressed (P < 0.05) between comparison groups. Hierarchical clustering of those genes differentially expressed between groups by IPA analysis was performed using BRB-Array Tools v.3.8.1. RESULTS: The majority of patients were characterized by the presence of comorbidities and the absence of immunosuppressive conditions. pH1N1 specific antibody production was observed around day 9 from disease onset and defined an early period of innate immune response and a late period of adaptive immune response to the virus. The most severe patients (n = 12) showed persistence of viral secretion. Seven of the most severe patients died. During the late phase, the most severe patient group had impaired expression of a number of genes participating in adaptive immune responses when compared to less severe patients. These genes were involved in antigen presentation, B-cell development, T-helper cell differentiation, CD28, granzyme B signaling, apoptosis and protein ubiquitination. Patients with the poorest outcomes were characterized by proinflammatory hypercytokinemia, along with elevated levels of immunosuppressory cytokines (interleukin (IL)-10 and IL-1ra) in serum. CONCLUSIONS: Our findings suggest an impaired development of adaptive immunity in the most severe cases of pandemic influenza, leading to an unremitting cycle of viral replication and innate cytokine-chemokine release. Interruption of this deleterious cycle may improve disease outcome.The study was scientifically sponsored by the Spanish Society for Critical Care Medicine (SEMICYUC). Funding: MICCIN-FIS/JCYL-IECSCYL-SACYL (Spain): Programa de Investigación Comisionada en Gripe, GR09/0021-EMER07/050- PI081236-RD07/0067. CIHR-NIH-Sardinia Recherché-LKSF Canada support DJK.S

Factors associated with the need of parenteral nutrition in critically ill patients after the initiation of enteral nutrition therapy

Background and aimsDespite enteral nutrition (EN) is the preferred route of nutrition in patients with critical illness, EN is not always able to provide optimal nutrient provision and parenteral nutrition (PN) is needed. This is strongly associated with gastrointestinal (GI) complications, a feature of gastrointestinal dysfunction and disease severity. The aim of the present study was to investigate factors associated with the need of PN after start of EN, together with the use and complications associated with EN.MethodsAdult patients admitted to 38 Spanish intensive care units (ICUs) between April and July 2018, who needed EN therapy were included in a prospective observational study. The characteristics of EN-treated patients and those who required PN after start EN were analyzed (i.e., clinical, laboratory and scores).ResultsOf a total of 443 patients, 43 (9.7%) received PN. One-third (29.3%) of patients presented GI complications, which were more frequent among those needing PN (26% vs. 60%, p = 0.001). No differences regarding mean energy and protein delivery were found between patients treated only with EN (n = 400) and those needing supplementary or total PN (n = 43). Abnormalities in lipid profile, blood proteins, and inflammatory markers, such as C-Reactive Protein, were shown in those patients needing PN. Sequential Organ Failure Assessment (SOFA) on ICU admission (Hazard ratio [HR]:1.161, 95% confidence interval [CI]:1.053–1.281, p = 0.003) and modified Nutrition Risk in Critically Ill (mNUTRIC) score (HR:1.311, 95% CI:1.098–1.565, p = 0.003) were higher among those who needed PN. In the multivariate analysis, higher SOFA score (HR:1.221, 95% CI:1.057–1.410, p = 0.007) and higher triglyceride levels on ICU admission (HR:1.004, 95% CI:1.001–1.007, p = 0.003) were associated with an increased risk for the need of PN, whereas higher albumin levels on ICU admission (HR:0.424, 95% CI:0.210–0.687, p = 0.016) was associated with lower need of PN.ConclusionA higher SOFA and nutrition-related laboratory parameters on ICU admission may be associated with the need of PN after starting EN therapy. This may be related with a higher occurrence of GI complications, a feature of GI dysfunction.Clinical trial registrationClinicalTrials.gov: NCT03634943

Nurses' perceptions of aids and obstacles to the provision of optimal end of life care in ICU

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