Hyperoxemia during resuscitation of trauma patients and increased intensive care unit length of stay: inverse probability of treatment weighting analysis.

BACKGROUND: Information on hyperoxemia among patients with trauma has been limited, other than traumatic brain injuries. This study aimed to elucidate whether hyperoxemia during resuscitation of patients with trauma was associated with unfavorable outcomes. METHODS: A post hoc analysis of a prospective observational study was carried out at 39 tertiary hospitals in 2016-2018 in adult patients with trauma and injury severity score (ISS) of > 15. Hyperoxemia during resuscitation was defined as PaO2 of ≥ 300 mmHg on hospital arrival and/or 3 h after arrival. Intensive care unit (ICU)-free days were compared between patients with and without hyperoxemia. An inverse probability of treatment weighting (IPW) analysis was conducted to adjust patient characteristics including age, injury mechanism, comorbidities, vital signs on presentation, chest injury severity, and ISS. Analyses were stratified with intubation status at the emergency department (ED). The association between biomarkers and ICU length of stay were then analyzed with multivariate models. RESULTS: Among 295 severely injured trauma patients registered, 240 were eligible for analysis. Patients in the hyperoxemia group (n = 58) had shorter ICU-free days than those in the non-hyperoxemia group [17 (10-21) vs 23 (16-26), p < 0.001]. IPW analysis revealed the association between hyperoxemia and prolonged ICU stay among patients not intubated at the ED [ICU-free days = 16 (12-22) vs 23 (19-26), p = 0.004], but not among those intubated at the ED [18 (9-20) vs 15 (8-23), p = 0.777]. In the hyperoxemia group, high inflammatory markers such as soluble RAGE and HMGB-1, as well as low lung-protective proteins such as surfactant protein D and Clara cell secretory protein, were associated with prolonged ICU stay. CONCLUSIONS: Hyperoxemia until 3 h after hospital arrival was associated with prolonged ICU stay among severely injured trauma patients not intubated at the ED. TRIAL REGISTRATION: UMIN-CTR, UMIN000019588 . Registered on November 15, 2015.

Association between low body mass index and increased 28-day mortality of severe sepsis in Japanese cohorts.

Current research regarding the association between body mass index (BMI) and altered clinical outcomes of sepsis in Asian populations is insufficient. We investigated the association between BMI and clinical outcomes using two Japanese cohorts of severe sepsis (derivation cohort, Chiba University Hospital, n = 614; validation cohort, multicenter cohort, n = 1561). Participants were categorized into the underweight (BMI < 18.5) and non-underweight (BMI ≥ 18.5) groups. The primary outcome was 28-day mortality. Univariate analysis of the derivation cohort indicated increased 28-day mortality trend in the underweight group compared to the non-underweight group (underweight 24.4% [20/82 cases] vs. non-underweight 16.0% [85/532 cases]; p = 0.060). In the primary analysis, multivariate analysis adjusted for baseline imbalance revealed that patients in the underweight group had a significantly increased 28-day mortality compared to those in the non-underweight group (p = 0.031, adjusted odds ratio [OR] 1.91, 95% confidence interval [CI] 1.06-3.46). In a repeated analysis using a multicenter validation cohort (underweight n = 343, non-underweight n = 1218), patients in the underweight group had a significantly increased 28-day mortality compared to those in the non-underweight group (p = 0.045, OR 1.40, 95% CI 1.00-1.97). In conclusion, patients with a BMI < 18.5 had a significantly increased 28-day mortality compared to those with a BMI ≥ 18.5 in Japanese cohorts with severe sepsis.

Clinical characteristics of patients with severe sepsis and septic shock in relation to bacterial virulence of beta-hemolytic Streptococcus and Streptococcus pneumoniae.

AIM: Combined detailed analysis of patient characteristics and treatment as well as bacterial virulence factors, which all play a central role in the cause of infections leading to severe illness, has not been reported. We aimed to describe the patient characteristics (Charlson comorbidity index [CCI]), treatment (3-h bundle), and outcomes in relation to bacterial virulence of Streptococcus pneumoniae and beta-hemolytic Streptococcus (BHS). METHODS: This sepsis primary study is part of the larger Focused Outcomes Research in Emergency Care in Acute Respiratory Distress Syndrome, Sepsis and Trauma (FORECAST) study, a multicenter, prospective cohort study. We included patients diagnosed with S. pneumoniae and BHS sepsis and examined virulence, defining the high-virulence factor as follows: S. pneumoniae serotype 3, 31, 11A, 35F, and 17F; Streptococcus pyogenes, emm 1; Streptococcus agalactiae, III; and Streptococcus dysgalactiae ssp. equisimilis, emm typing pattern stG 6792. Included patients were divided into high and normal categories based on the virulence factor. RESULTS: Of 1,184 sepsis patients enrolled in the Japanese Association for Acute Medicine's FORECAST study, 62 were included in the current study (29 cases with S. pneumoniae sepsis and 33 with BHS). The CCI and completion of a 3-h bundle did not differ between normal and high virulence groups. Risk of 28-day mortality was significantly higher for high-virulence compared to normal-virulence when adjusted for CCI and completion of a 3-h bundle (Cox proportional hazards regression analysis, hazard ratio 3.848; 95% confidence interval, 1.108-13.370; P = 0.034). CONCLUSION: The risk of 28-day mortality was significantly higher for patients with high-virulence compared to normal-virulence bacteria.

Risk modifiers of acute respiratory distress syndrome in patients with non-pulmonary sepsis: a retrospective analysis of the FORECAST study.

BACKGROUND: Predisposing conditions and risk modifiers instead of causes and risk factors have recently been used as alternatives to identify patients at a risk of acute respiratory distress syndrome (ARDS). However, data regarding risk modifiers among patients with non-pulmonary sepsis is rare. METHODS: We conducted a secondary analysis of the multicenter, prospective, Focused Outcomes Research in Emergency Care in Acute Respiratory Distress Syndrome, Sepsis and Trauma (FORECAST) cohort study that was conducted in 59 intensive care units (ICUs) in Japan during January 2016-March 2017. Adult patients with severe sepsis caused by non-pulmonary infection were included, and the primary outcome was having ARDS, defined as meeting the Berlin definition on the first or fourth day of screening. Multivariate logistic regression modeling was used to identify risk modifiers associated with ARDS, and odds ratios (ORs) and their 95% confidence intervals were reported. The following explanatory variables were then assessed: age, sex, admission source, body mass index, smoking status, congestive heart failure, chronic obstructive pulmonary disease, diabetes mellitus, steroid use, statin use, infection site, septic shock, and acute physiology and chronic health evaluation (APACHE) II score. RESULTS: After applying inclusion and exclusion criteria, 594 patients with non-pulmonary sepsis were enrolled, among whom 85 (14.3%) had ARDS. Septic shock was diagnosed in 80% of patients with ARDS and 66% of those without ARDS (p = 0.01). APACHE II scores were higher in patients with ARDS [26 (22-33)] than in those without ARDS [21 (16-28), p < 0.01]. In the multivariate logistic regression model, the following were independently associated with ARDS: ICU admission source [OR, 1.89 (1.06-3.40) for emergency department compared with hospital wards], smoking status [OR, 0.18 (0.06-0.59) for current smoking compared with never smoked], infection site [OR, 2.39 (1.04-5.40) for soft tissue infection compared with abdominal infection], and APACHE II score [OR, 1.08 (1.05-1.12) for higher compared with lower score]. CONCLUSIONS: Soft tissue infection, ICU admission from an emergency department, and a higher APACHE II score appear to be the risk modifiers of ARDS in patients with non-pulmonary sepsis.

Trends in sepsis care in Japan: comparison of two sepsis cohort studies conducted by the Japanese Association for Acute Medicine.

Our analysis showed that improved compliance with sepsis bundles was associated with lower in-hospital mortality over a 7-year period in Japan, confirming that the SSC has been executed correctly in our country.

Early evaluation of severity in patients with severe sepsis: a comparison with "septic shock" - subgroup analysis of the Japanese Association for Acute Medicine Sepsis Registry (JAAM-SR).

Aim: The purpose of this subgroup analysis of a Japanese multicenter registry, the Japanese Association for Acute Medicine Sepsis Registry Advanced (JAAM-SR-Advanced), was to identify early outcome indicators for severe sepsis that are useful and more objective than "septic shock." Methods: Among 624 patients with severe sepsis registered in JAAM-SR-Advanced, 554 with valid serum lactate data were retrospectively studied. Hypotension before and after fluid resuscitation and the highest lactate values over the initial 24 h were compared for their ability to predict in-hospital mortality. Results: Of the study group, 155 (28.0%) patients were non-survivors and had significantly lower systolic blood pressures and higher lactate peaks. The mortality of 364 patients with initial hypotension was higher than those patients without it (32.7% versus 19.1%, P < 0.01). Patients with the worst lactate values ≥4 mmol/L had much higher mortality than other patients (P < 0.001). In an attempt to predict outcomes, we combined initial hypotension and the worst lactate values. The patient group with initial hypotension and the worst lactate values ≥4 mmol/L (183 patients, 33.0%) had a significantly higher mortality rate of 48.6% than the other groups (P < 0.01). Conclusion: The novel combined criterion of initial hypotension and the worst lactate values ≥4 mmol/L within the initial 24 h is potentially useful as a single outcome predictor for severe sepsis.

Impact of serum glucose levels on disease severity and outcome in patients with severe sepsis: an analysis from a multicenter, prospective survey of severe sepsis.

Aim: To determine whether glycemic abnormality and pre-existing diabetes are associated with disease severity and mortality in patients with severe sepsis. Methods: Six hundred and nineteen patients with severe sepsis were grouped into four categories according to their blood glucose levels (<100, 100-199, 200-299, and ≥300 mg/dL). We compared disease severity and mortality between glycemic categories. In addition, we examined whether there was any relationship with pre-existing diabetes status. Results: There were no significant differences in disseminated intravascular coagulation, Sequential Organ Failure Assessment, or Acute Physiology and Chronic Health Evaluation II scores and mortality rates between patients with or without pre-existing diabetes. However, in patients without pre-existing diabetes, those with blood glucose level <100 mg/dL had higher disseminated intravascular coagulation, Sequential Organ Failure Assessment, and Acute Physiology and Chronic Health Evaluation II scores than those with levels of 100-299 mg/dL. In addition, those with level ≥300 mg/dL had a higher hospital mortality rate than those with levels of 100-199 mg/dL (odds ratio = 4.837). Multivariate logistic regression analysis revealed that a blood glucose level ≥300 mg/dL is an independent predictor of hospital mortality in these patients. In contrast, no significant differences among severity scores or mortality were observed in patients with pre-existing diabetes. Conclusions: In patients with severe sepsis, the impact of glycemic abnormality on disease severity and hospital mortality depends on the pre-existing diabetes status. Specifically, a blood glucose level ≥300 mg/dL may be associated with increased mortality in patients without pre-existing diabetes.

Olive Oil Polyphenols Differentially Inhibit Smooth Muscle Cell Proliferation through a G1/S Cell Cycle Block Regulated by ERK1/2.

We hypothesized that polyphenols contained in olive oil play a role in reducing the risk of atherosclerosis. The aim of this study was to determine if the polyphenols in olive oil, oleuropein (Ole), hydroxytyrosol (HT), and tyrosol (Tyr) could inhibit smooth muscle cell (SMC) proliferation through its influence on cell cycle regulation. Bovine vascular SMC were cultured in the presence of Ole, HT, or Tyr at concentration of 1, 10, or 100 µmol/L. On days 1, 3, and 5, numbers of cells were counted. Cell cycle analysis was performed by flow cytometry on day 1 after SMC were stained with propidium iodide. Cell populations grown in the presence of Ole or HT at 100 µmol/L concentration were significantly inhibited after 5 days of exposure. Tyr had a similar tendency but it did not attain significance. Cell cycle analysis revealed that 66% of cells were in G1 phase in Ole group, compared with 48% in control group. To examine the cell cycle block between G1 and S phases, we performed Western blotting and found that ERK1/2 activation was inhibited by Ole or HT. We conclude that olive oil polyphenols could inhibit SMC proliferation through a cell cycle block between G1 and S phases which may be regulated by ERK1/2. These results demonstrate a mechanism by which olive oil consumption may be atheroprotective by inhibiting SMC proliferation.

Laminar shear, but not orbital shear, has a synergistic effect with thrombin stimulation on tissue factor expression in human umbilical vein endothelial cells.

INTRODUCTION: High levels of tissue factor (TF) have been associated with atherosclerotic plaques. The specific pathways linked to TF expression in endothelial cells (ECs) have not been well defined. This study compared TF expression in human umbilical vein ECs (HUVECs) exposed to laminar shear stress (LSS) using a parallel flow chamber and to orbital shear stress (OSS) using an orbital shaker. We also compared the effects of thrombin (TH) stimulation of ECs exposed to different shear forces on the expression of TF and investigated the role that second messengers, p38 and extracellular signal-regulated kinase 1 and 2 (ERK1/2), had in the EC response. METHODS: HUVECs were subjected to 2, 4, or 6 hours of LSS or OSS in the presence or absence of 4 U/mL of TH. Western blot analysis of ERK1/2 and p38 activation and polymerase chain reaction analysis of TF in the presence of inhibitors to these second messengers was performed in HUVECs subjected to OSS or LSS in the presence or absence of TH. RESULTS: TF expression was increased and peaked at 2 hours in all HUVECs exposed to LSS or TH. Stimulation of static HUVECs with TH resulted in an increase in TF expression of 5.68 ± 1.58-, 3.80 ± 1.21-, and 2.54 ± 0.38-fold at 2, 4, and 6 hours, respectively (n = 6 experiments). In the absence of TH, HUVECs exposed to LSS demonstrated a 9.51 ± 0.62-, 7.31 ± 1.43-, and 4.39 ± 1.32-fold increase in TF expression at 2, 4, and 6 hours, respectively (n = 6 experiments). TF was increased significantly more when exposed to LSS in the presence of TH (18.85 ± 1.43-, 15.05 ± 0.95-, and 8.91 ± 1.06-fold increases at 2, 4, and 6 hours, respectively [n = 6 experiments], P < .01). Between-group analysis showed a significant difference between groups (P < .001). OSS did not significantly increase TF expression in the presence or absence of TH. ERK1/2 and p38 activation was increased in LSS and LSS + TH but not in OSS or OSS + TH (n = 3 experiments). CONCLUSION: LSS and TH independently increased TF expression, but OSS did not. LSS + TH stimulation showed a synergistic effect, which suggests that these mechanical and chemical stimuli work through different pathways or that an intracellular interaction between TH and LSS may be present that does not occur in OSS.