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Purpose: Acute respiratory distress syndrome (ARDS) remains a major cause of death. Epidemiology should be continually examined to refine therapeutic strategies for ARDS. We aimed to elucidate demographics, treatments, and outcomes of ARDS in Japan., Methods: This is a prospective cohort study for ARDS. We included adult patients admitted to intensive care units through emergency and critical care departments who satisfied the American-European Consensus Conference (AECC) acute lung injury (ALI) criteria. In addition, the fulfillment of the Berlin definition was assessed. Logistic regression analyses were used to examine the association of independent variables with outcomes., Results: Our study included 166 patients with AECC ALI from 34 hospitals in Japan; among them, 157 (94.6%) fulfilled the Berlin definition. The proportion of patients with PaO2/FIO2 ≤ 100, patients under invasive positive pressure ventilation (IPPV), and in-hospital mortality was 39.2%, 92.2%, and 38.0% for patients with AECC ALI and 38.9%, 96.8%, and 37.6% for patients with Berlin ARDS, respectively. The area of lung infiltration was independently associated with outcomes of ARDS. Low-mid-tidal volume ventilation was performed in 75% of patients under IPPV. Glucocorticoid use was observed in 54% patients, and it was positively associated with mortality., Conclusions: Our study included a greater percentage of patients with ARDS with high severity and found that the overall mortality was 38%. The management of ARDS in Japan was characterized by high the utilization rate of glucocorticoids, which was positively associated with mortality.

Purpose: Hospital services are reduced during off-hour such as nighttime or weekend. Investigations of the off-hour effect on initial management and outcomes in sepsis are very limited. Thus, we tested the hypothesis that patients who were diagnosed with severe sepsis during the nighttime or on non-business days had altered initial management and clinical outcomes., Materials and Methods: Patients with severe sepsis from 59 ICUs between 2016 and 2017 were enrolled. The patients were categorized according to the diagnosis time or day and were then compared. The primary outcome was in-hospital mortality., Results: One thousand one hundred and forty-eight patients were analyzed; 769 daytime patients, vs. 379 nighttime patients, and 791 business day patients vs. 357 non-business day patients. There were no significant differences in in-hospital mortality between either daytime and nighttime (24.4% vs. 21.4%, P = .27; nighttime, adjusted odds ratio [OR] 1.17, 95% confidence interval [CI], 0.87-1.59, P = .30) or between business and non-business days (22.9% vs. 24.6%, P = .55; non-business day, adjusted OR 0.85, 95% CI 0.60-1.22, P = .85). Time to antibiotics was significantly shorter in the nighttime (114 vs. 89 min, P = .0055)., Conclusions: Nighttime and weekends were not associated with increased in-hospital mortality of severe sepsis., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Genetic variants are associated with altered clinical outcome of patients with sepsis and cardiovascular diseases. Common gene signaling pathways may be involved in the pathophysiology of these diseases. A better understanding of genetic commonality among these diseases may enable the discovery of important genes, signaling pathways, and therapeutic targets for these diseases. We investigated the common genetic factors by a systematic search of the literature. Twenty-four genes (ADRB2, CD14, FGB, FV, HMOX1, IL1B, IL1RN, IL6, IL10, IL17A, IRAK1, MASP2, MBL, MIR608, MIF, NOD2, PCSK9, PPARG, PROC, SERPINE1, SOD2, SVEP1, TF, TIRAP, TLR1) were extracted as reported genetic variations associated with altered outcome of both sepsis and cardiovascular diseases. Of these genes, the adverse allele (or combinations) was same in nine (ADRB2, FV, HMOX1, IL6, MBL, MIF, NOD2, PCSK9, SERPINE1), and the effect appears to be in the same direction in both sepsis and cardiovascular disease. Shared gene signaling pathways suggest that these are true biological results and could point to overlapping drug targets in sepsis and cardiovascular disease., (Copyright © 2019 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Liver abscess remains a life-threatening disease, particularly when it results in systemic organ failure necessitating intensive care. Only few cases of respiratory failure caused by liver abscess and treated with veno-venous extracorporeal membrane oxygenation (ECMO) have been reported. Here we present a case of liver abscess with rapid progression of multiple organ dysfunction, including severe acute respiratory failure on admission to the intensive care unit (ICU). Upon admission, we immediately initiated artificial organ support systems, including ventilator, continuous renal replacement therapy, and cardiovascular drug infusion for septic multiple organ failure and source control. Despite this initial management, respiratory failure deteriorated and V-V ECMO was introduced. The case developed abdominal compartment syndrome, for which we performed a bedside decompressive laparotomy in the ICU. The case gradually recovered from multiple organ failure and was discharged from the ICU on day 22 and from the hospital on day 53. Since liver abscess is potentially lethal and respiratory failure on admission is an additional risk factor of mortality, V-V ECMO may serve as an adjunctive choice of artificial organ support for cases of severe acute respiratory failure caused by liver abscess.

Background: Whether hospital bed number and rapid response system (RRS) call rate is associated with the clinical outcomes of patients who have RRS activations is unknown. We test a hypothesis that hospital volume and RRS call rates are associated with the clinical outcomes of patients with RRSs.Methods: This is a retrospective chart analysis of an existing dataset associated with In-Hospital Emergency Registry in Japan. In the present study, 4818 patients in 24 hospitals from April 2014 to March 2018 were analyzed. Primary outcome variable was an unplanned intensive care unit (ICU) admission after RRS activation.Results: In the primary analysis of the study using a multivariate analysis adjusting potential confounding factors, higher RRS call rate was significantly associated with decreased unplanned ICU admissions (P < 0.0001, Odds ratio [OR] 0.95, 95% confidence interval [CI] 0.92-0.98), but there was no significant association of hospital volume with unplanned ICU admissions (P = 0.44). In the secondary analysis of the study, there was a non-significant trend of increased cardiac arrest on arrival at the location of the RRS provider at large-volume hospitals (P = 0.084, OR 1.16, 95% CI 0.98-1.38). Large-volume hospitals had a significantly higher 1-month mortality rate (P = 0.0040, OR 1.10, 95% CI 1.03-1.18).Conclusion: Hospitals with increased RRS call rates had significantly decreased unplanned ICU admission in patients who had RRS activations. Patients who had RRS activations at large-volume hospitals had an increased 1-month mortality rate. [ABSTRACT FROM AUTHOR]

Objectives: Mortality from septic shock is highly heritable. The identification of causal genetic factors is insufficient. To discover key contributors, we first identified nonsynonymous single-nucleotide polymorphisms in conserved genomic regions that are predicted to have significant effects on protein function. We then test the hypothesis that these nonsynonymous single-nucleotide polymorphisms across the genome alter clinical outcome of septic shock. Design: Genetic-association study plus in vitro experiment using primary cells plus in silico analysis using genomic DNA and protein database. Setting: Twenty-seven ICUs at academic teaching centers in Canada, Australia, and the United States. Patients: Patients with septic shock of European ancestry (n = 520). Interventions: Patients with septic shock were genotyped for 843 nonsynonymous single-nucleotide polymorphisms in conserved regions of the genome and are predicted to have damaging effects from the protein sequence. Measurements and Main Results: The primary outcome variable was 28-day mortality. Secondary outcome variables were organ dysfunction. Productions of adhesion molecules including interleukin- 8, growth-regulated oncogene-a, monocyte chemoattractant protein-1, and monocyte chemoattractant protein-3 were measured in human umbilical vein endothelial cells after SVEP1 gene silencing by RNA interference. Patients with septic shock having the SVEP1 C allele of nonsynonymous single-nucleotide polymorphism, SVEP1 c.2080A>C (p. Gln581His, rs10817033), had a significant increase in the hazard of death over the 28 days (hazard ratio, 1.72; 95% Cl, 1.31-2.26; p = 9.7 × 10-5) and increased organ dysfunction and needed more organ support (p < 0.05). Silencing SVEP1 significantly increased interleukin-8, growth-regulated oncogene-a, monocyte chemoattractant protein-1, monocyte chemoattractant protein-3 production in human umbilical vein endothelial cells under lipopolysaccharide stimulation (p < 0.01). Conclusions: C allele of SVEP1 c.2080A>C (p. Gln581His) single-nucleotide polymorphism, a non-synonymous singlenucleotide polymorphism in conserved regions and predicted to have damaging effects on protein structure, was associated with increased 28-day mortality and organ dysfunction of septic shock. SVEP1 appears to regulate molecules of the leukocyte adhesion pathway. [ABSTRACT FROM AUTHOR]

ABSTRACT Background and Objective: Interleukin-8 (IL-8) is a central chemokine in acute respiratory distress syndrome (ARDS), and the IL-8 gene contains a functional single nucleotide polymorphism (SNP) −251A/T in its promoter region. We hypothesized that IL-8 −251A/T SNP is associated with PaO2/FiO2 in critically ill patients. Methods: We conducted genetic-association studies in intensive care units at academic teaching centres using a derivation septic shock cohort (vasopressin and septic shock trial (VASST), n = 467) and a validation post-cardiopulmonary bypass surgery cohort (CPB, n = 739) of Caucasian patients. Patients in both cohorts were genotyped for IL-8 −251A/T. The primary outcome variable in both cohorts was the fraction of patients who had a PaO2/FiO2 < 200. IL-8 mRNA expression was measured in genotyped lymphoblastoid cells in vitro. Results: The frequency of the patients with PaO2/FiO2 <200 was significantly greater in patients who had the AA genotype of −251A/T than in patients who had the AT or TT genotypes in both VASST (AA = 60.8% vs AT and TT = 53.8% and 48.0%, P = 0.038) and the CPB cohort (AA = 37.0% vs AT and TT = 27.0% and 26.0%, P = 0.039). Patients having the AA genotype had a higher probability to remain on mechanical ventilation ( P = 0.047) in the first 14 days. Lymphoblastoid cells having the AA genotype had significantly higher IL-8 mRNA expression than cells having the AT or TT genotype ( P = 0.022). Conclusions: Critically ill Caucasian patients who had the AA genotype of IL-8 −251A/T had an increased risk of PaO2/FiO2 <200. The AA genotype was associated with greater IL-8 mRNA expression than the AT or TT genotypes. [ABSTRACT FROM AUTHOR]

The article presents a study which tested the hypothesis that single nucleotide polymorphisms in angiotensin II pathway genes change the outcome of septic shock. The study involved 589 patients who have experienced derivation septic shock, 616 individuals with validation septic shock and 551 with coronary bypass surgery. Results revealed that angiotensin type II receptor-associated protein was associated with increase angiotensin II type 1 receptor-associated protein expansion, decreased blood pressure, and increased heart rate.

Abstract: Objectives: To investigate the usefulness of analysis of single nucleotide polymorphism (SNP) using a newly developed DNA chip assay involving single base extension(SBE) and subsequent hybridization in cytokine-related genes in critical care patients. Design and methods: Genotyping was performed in 76 ICU patients admitted to the ICU. First, the DNA samples from 58 patients were subjected to PCR and SBE conditioning for DNA. Second, another 18 patients were subjected to genotyping for SNPs in IL-6 −596G/A, −572C/G, −174G/C, TNF-α −308G/A, −238G/A, IL-1β −511C/T and −31T/C by both TaqMan and DNA chip method, and by DNA direct sequencing prospectively. Results: First, PCR and SBE condition were established with initial sample sets, which were consistent with results by TaqMan method. Second, no difference was observed between two assay methods in prospective validation set. Conclusions: The genotyping assay using the new chip was developed and its usefulness was confirmed. [Copyright &y& Elsevier]