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Background: Diagnosing sepsis remains difficult because it is not a single disease but a syndrome with various pathogen- and host factor-associated symptoms. Sepsis-3 was established to improve risk stratification among patients with infection based on organ failures, but it has been still controversial compared with previous definitions. Therefore, we aimed to describe characteristics of patients who met sepsis-2 (severe sepsis) and sepsis-3 definitions. Methods: This was a multicenter, prospective cohort study conducted by 22 intensive care units (ICUs) in Japan. Adult patients (≥ 16 years) with newly suspected infection from December 2017 to May 2018 were included. Those without infection at final diagnosis were excluded. Patient's characteristics and outcomes were described according to whether they met each definition or not. Results: In total, 618 patients with suspected infection were admitted to 22 ICUs during the study, of whom 530 (85.8%) met the sepsis-2 definition and 569 (92.1%) met the sepsis-3 definition. The two groups comprised different individuals, and 501 (81.1%) patients met both definitions. In-hospital mortality of study population was 19.1%. In-hospital mortality among patients with sepsis-2 and sepsis-3 patients was comparable (21.7% and 19.8%, respectively). Patients exclusively identified with sepsis-2 or sepsis-3 had a lower mortality (17.2% vs. 4.4%, respectively). No patients died if they did not meet any definitions. Patients who met sepsis-3 shock definition had higher in-hospital mortality than those who met sepsis-2 shock definition. Conclusions: Most patients with infection admitted to ICU meet sepsis-2 and sepsis-3 criteria. However, in-hospital mortality did not occur if patients did not meet any criteria. Better criteria might be developed by better selection and combination of elements in both definitions. Trial registration: UMIN000027452 [ABSTRACT FROM AUTHOR]

Background: Elderly patients have a blunted host response, which may influence vital signs and clinical outcomes of sepsis. This study was aimed to investigate whether the associations between the vital signs and mortality are different in elderly and non-elderly patients with sepsis.Methods: This was a retrospective observational study. A Japanese multicenter sepsis cohort (FORECAST, n = 1148) was used for the discovery analyses. Significant discovery results were tested for replication using two validation cohorts of sepsis (JAAMSR, Japan, n = 624; SPH, Canada, n = 1004). Patients were categorized into elderly and non-elderly groups (age ≥ 75 or < 75 years). We tested for association between vital signs (body temperature [BT], heart rate, mean arterial pressure, systolic blood pressure, and respiratory rate) and 90-day in-hospital mortality (primary outcome).Results: In the discovery cohort, non-elderly patients with BT < 36.0 °C had significantly increased 90-day mortality (P = 0.025, adjusted hazard ratio 1.70, 95% CI 1.07-2.71). In the validation cohorts, non-elderly patients with BT < 36.0 °C had significantly increased mortality (JAAMSR, P = 0.0024, adjusted hazard ratio 2.05, 95% CI 1.29-3.26; SPH, P = 0.029, adjusted hazard ratio 1.36, 95% CI 1.03-1.80). These differences were not observed in elderly patients in the three cohorts. Associations between the other four vital signs and mortality were not different in elderly and non-elderly patients. The interaction of age and hypothermia/fever was significant (P < 0.05).Conclusions: In septic patients, we found mortality in non-elderly sepsis patients was increased with hypothermia and decreased with fever. However, mortality in elderly patients was not associated with BT. These results illuminate the difference in the inflammatory response of the elderly compared to non-elderly sepsis patients. [ABSTRACT FROM AUTHOR]

Background: Dysglycemia is frequently observed in patients with sepsis. However, the relationship between dysglycemia and outcome is inconsistent. We evaluate the clinical characteristics, glycemic abnormalities, and the relationship between the initial glucose level and mortality in patients with sepsis. Methods: This is a retrospective sub-analysis of a multicenter, prospective cohort study. Adult patients with severe sepsis (Sepsis-2) were divided into groups based on blood glucose categories (<70 (hypoglycemia), 70–139, 140–179, and ≥180 mg/dL), according to the admission values. In-hospital mortality and the relationship between pre-existing diabetes and septic shock were evaluated. Results: Of 1158 patients, 69, 543, 233, and 313 patients were categorized as glucose levels <70, 70–139, 140–179, ≥180 mg/dL, respectively. Both the Acute Physiological and Chronic Health Evaluation II and Sequential Organ Failure Assessment (SOFA) scores on the day of enrollment were higher in the hypoglycemic patients than in those with 70–179 mg/dL. The hepatic SOFA scores were also higher in hypoglycemic patients. In-hospital mortality rates were higher in hypoglycemic patients than in those with 70–139 mg/dL (26/68, 38.2% vs 43/221, 19.5%). A significant relationship between mortality and hypoglycemia was demonstrated only in patients without known diabetes. Mortality in patients with both hypoglycemia and septic shock was 2.5-times higher than that in patients without hypoglycemia and septic shock. Conclusions: Hypoglycemia may be related to increased severity and high mortality in patients with severe sepsis. These relationships were evident only in patients without known diabetes. Patients with both hypoglycemia and septic shock had an associated increased mortality rate. [ABSTRACT FROM AUTHOR]

Background/Aims: The optimal duration of hemoperfusion therapy with a polymyxin B-immobilized fiber column has not yet been verified. Methods: This analysis examined whether hemoperfusion therapy with a polymyxin B-immobilized fiber column lasting longer than 2 h (prolonged polymyxin) improved outcomes for patients with septic shock compared to 2-h polymyxin therapy (sub-analysis of data from the DESIRE trial). Results: The 2-h and prolonged polymyxin groups contained 22 and 14 patients, respectively. Both groups had similar characteristics. The polymyxin duration per session in the prolonged polymyxin group was significantly longer (median, 5.5 h) than in the 2-h polymyxin group (p < 0.01). The 28-day mortality rate was significantly higher in the 2-h polymyxin group (7, 31.8%) than in the prolonged polymyxin group (0, 0%; p = 0.019). Conclusion: Prolonged polymyxin therapy might be associated with better clinical outcomes than 2-h polymyxin therapy in patients with septic shock. Video Journal Club "Cappuccino with Claudio Ronco" at http://www.karger.com/?doi=491744. [ABSTRACT FROM AUTHOR]

Background and Purpose The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J‐SSCG 2016), a Japanese‐specific set of clinical practice guidelines for sepsis and septic shock created jointly by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine, was first released in February 2017 in Japanese. An English‐language version of these guidelines was created based on the contents of the original Japanese‐language version. Methods: Members of the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine were selected and organized into 19 committee members and 52 working group members. The guidelines were prepared in accordance with the Medical Information Network Distribution Service (Minds) creation procedures. The Academic Guidelines Promotion Team was organized to oversee and provide academic support to the respective activities allocated to each Guideline Creation Team. To improve quality assurance and workflow transparency, a mutual peer review system was established, and discussions within each team were open to the public. Public comments were collected once after the initial formulation of a clinical question (CQ), and twice during the review of the final draft. Recommendations were determined to have been adopted after obtaining support from a two‐thirds (>66.6%) majority vote of each of the 19 committee members. Results: A total of 87 CQs were selected among 19 clinical areas, including pediatric topics and several other important areas not covered in the first edition of the Japanese guidelines (J‐SSCG 2012). The approval rate obtained through committee voting, in addition to ratings of the strengths of the recommendation and its supporting evidence were also added to each recommendation statement. We conducted meta‐analyses for 29 CQs. Thirty seven CQs contained recommendations in the form of an expert consensus due to insufficient evidence. No recommendations were provided for 5 CQs. Conclusions: Based on the evidence gathered, we were able to formulate Japanese‐specific clinical practice guidelines that are tailored to the Japanese context in a highly transparent manner. These guidelines can easily be used not only by specialists, but also by non‐specialists, general clinicians, nurses, pharmacists, clinical engineers, and other healthcare professionals.

Background: Accurate and early identification of infection sites might help to drive crucial decisions regarding the treatment of sepsis. We aimed to determine the clinical and etiological features of infection according to sites among patients with severe sepsis in Japan. Methods: This secondary analysis of a multicenter, prospective cohort study included 59 intensive care units (ICU) and proceeded between January 2016 and March 2017. The study cohort comprised 1184 adults (≥ 16 years) who were admitted to an ICU with severe sepsis and septic shock diagnosed according to the sepsis-2 criteria. Sites of infection diagnosed by physicians in charge at the time of arrival comprised the lung, abdomen, urinary tract, soft tissue, bloodstream, central nervous system (CNS), and undifferentiated infections. The primary outcome was in-hospital mortality. Results: The most common sites of infection were the lungs (31.0%), followed by intra-abdominal sites (26.3%), the urinary tract (18.4%), and soft tissue (10.9%). The characteristics of the patients with severe sepsis across seven major suspected infection sites were heterogeneous. Septic shock was more frequent among patients with intra-abdominal (72.2%) and urinary tract (70.2%) infections than other sites. The in-hospital mortality rate due to severe sepsis and septic shock of a pooled sample was 23.4% (range, 11.9% [urinary tract infection] to 47.6% [CNS infection]). After adjusting for clinical background, sepsis severity, and stratification according to the presence or absence of shock, variations in hospital mortality across seven major sites of infection remained essentially unchanged from those for crude in-hospital mortality; adjusted in-hospital mortality rates ranged from 7.7% (95%CI, − 0.3 to 15.8) for urinary tract infection without shock to 58.3% (95%CI, 21.0–95.7) for CNS infection with shock in a generalized estimating equation model. Intra-abdominal and urinary tract infections were statistically associated with less in-hospital mortality than pneumonia. Infections of the CNS were statistically associated with higher in-hospital mortality rates than pneumonia in a logistic regression model, but not in the generalized estimating equation model. Conclusions: In-hospital mortality and clinical features of patients with severe sepsis and septic shock were heterogeneous according to sites of infection. [ABSTRACT FROM AUTHOR]

Sepsis leads to coagulopathy by the activation of inflammatory mediators and vascular endothelial cell injury. A number of biomarkers are used to evaluate coagulopathy on sepsis. Fibrinogen and antithrombin activity have been reported as biomarkers of coagulopathy; however, the utility of these two markers has not been well established. This study aimed to evaluate the detailed association between these two markers and clinical outcomes in sepsis patients. This was a post hoc analysis of a multicenter, prospective cohort study conducted in 59 intensive care units throughout Japan from January 2016 to March 2017. We included 1103 adult patients with severe sepsis based on the Sepsis-2 criteria. The associations between the coagulation markers and in-hospital mortality were examined using linear and non-linear logistic regression analyses. We also evaluated the associations between the coagulation markers and disseminated intravascular coagulation (DIC) scores. The International Society on Thrombosis and Haemostasis overt DIC score was calculated after subtracting the fibrinogen component. The decreased levels of the fibrinogen and antithrombin activity were significantly associated with an increase in mortality (P = 0.011 and 0.002, respectively). In addition, cubic spline regression demonstrated that mortality sharply increased at a fibrinogen level of approximately <200 mg/dL and at an antithrombin activity of approximately <50%. Similarly, the decreased levels of the two markers non-linearly correlated with the elevation of DIC score. The fibrinogen level and antithrombin activity should be reconsidered as unique biomarkers for sepsis and sepsis-induced DIC. • A cubic spline model assessed nonlinear associations between markers and outcomes. • Fibrinogen levels of <200 mg/dL sharply increased the risk of mortality. • Antithrombin activity of <50% sharply increased the risk of mortality. • Fibrinogen and antithrombin were also non-linearly associated with DIC severity. [ABSTRACT FROM AUTHOR]

Disseminated intravascular coagulation (DIC) associated with multiple organ dysfunction syndrome (MODS) plays pivotal roles in severe sepsis. We performed a multicenter, prospective data collection study and retrospectively analyzed the data to confirm the role of DIC in severe sepsis. Eligible patients were ICU patients who met the definitions of severe sepsis, and 1013 patients were included. DIC scores as well as disease severity and the development of MODS on the day of the diagnosis of severe sepsis (day 0) and at day 3 were evaluated. The primary outcome was hospital mortality, and MODS on days 0 and 3 was the secondary outcomes. The overall mortality rate of severe sepsis was 21.5%, and the prevalence of DIC was 50.9% (516/1013). DIC patients were more seriously ill and exhibited a higher prevalence of MODS (32.0% vs. 13.1%) on day 0 and worse mortality rate (24,8% vs. 17.5%) than non-DIC patients. DIC patients also showed a lower survival probability than non-DIC patients (Log rank p = 0.028). Logistic regression analyses after propensity score adjustment for potential confounders confirmed a significant association between DIC and MODS and hospital death in the patients with severe sepsis. The new development of DIC and persistent DIC from days 0 to 3 were associated with a high incidence of MODS and low survival probability. The mortality rate of severe sepsis has been improved; however, DIC is still associated with the poor prognosis of these patients. Evaluating the dynamic changes in the DIC status may improve the prediction capability. • The role of DIC in severe sepsis remains unclear. • An association between DIC and the prognosis of severe sepsis was investigated. • Mortality of DIC associated with organ dysfunctions in severe sepsis was still high. • Changes in DIC status were important for predicting the prognosis of severe sepsis. [ABSTRACT FROM AUTHOR]

Additionally, based on the results of the policytree algorithm, we selected the potential treatment targets of PMX as patients with septic shock and coagulopathy of PT-INR>=1.4 (46% of the derivation cohort). However, given that the trial estimated the treatment effects of PMX only in certain prespecified patient groups, we aimed to find previously unidentified patient subgroups with septic shock who may benefit from targeted use of PMX using a machine-leaning based algorithm. B Introduction: b Polymyxin B hemoperfusion (PMX) was not shown to reduce 28-day mortality in patients with septic shock in the EUPHRATES trial. [Extracted from the article]