COAGULOPATHY PARAMETERS PREDICTIVE OF OUTCOMES IN SEPSIS-INDUCED ACUTE RESPIRATORY DISTRESS SYNDROME: A SUBANALYSIS OF THE TWO PROSPECTIVE MULTICENTER COHORT STUDIES.

ABSTRACT: Background: Although coagulopathy is often observed in acute respiratory distress syndrome (ARDS), its clinical impact remains poorly understood. Objectives: This study aimed to clarify the coagulopathy parameters that are clinically applicable for prognostication and to determine anticoagulant indications in sepsis-induced ARDS. Method: This study enrolled patients with sepsis-derived ARDS from two nationwide multicenter, prospective observational studies. We explored coagulopathy parameters that could predict outcomes in the Focused Outcome Research on Emergency Care for Acute Respiratory Distress Syndrome, Sepsis, and Trauma (FORECAST) cohort, and the defined coagulopathy criteria were validated in the Sepsis Prognostication in Intensive Care Unit and Emergency Room-Intensive Care Unit (SPICE-ICU) cohort. The correlation between anticoagulant use and outcomes was also evaluated. Results: A total of 181 patients with sepsis-derived ARDS in the FORECAST study and 61 patients in the SPICE-ICU study were included. In a preliminary study, we found the set of prothrombin time-international normalized ratio ≥1.4 and platelet count ≤12 × 10 4 /µL, and thrombocytopenia and elongated prothrombin time (TEP) coagulopathy as the best coagulopathy parameters and used it for further analysis; the odds ratio (OR) of TEP coagulopathy for in-hospital mortality adjusted for confounding was 3.84 (95% confidence interval [CI], 1.66-8.87; P = 0.005). In the validation cohort, the adjusted OR for in-hospital mortality was 32.99 (95% CI, 2.60-418.72; P = 0.002). Although patients without TEP coagulopathy showed significant improvements in oxygenation over the first 4 days, patients with TEP coagulopathy showed no significant improvement (ΔPaO 2 /FiO 2 ratio, 24 ± 20 vs. 90 ± 9; P = 0.026). Furthermore, anticoagulant use was significantly correlated with mortality and oxygenation recovery in patients with TEP coagulopathy but not in patients without TEP coagulopathy. Conclusion: Thrombocytopenia and elongated prothrombin time coagulopathy is closely associated with better outcomes and responses to anticoagulant therapy in sepsis-induced ARDS, and our coagulopathy criteria may be clinically useful.

Hyperoxia for sepsis and development of acute lung injury with increased mortality.

BACKGROUND: Supraphysiological oxygen administration causes unfavourable clinical outcomes in various diseases. This study aimed to determine whether hyperoxia would be associated with increased mortality in patients with severe infection. METHODS: A post-hoc analysis of a nationwide multicentre prospective observational study on sepsis (SPICE Study) was conducted, including adult patients admitted to the intensive care unit with available arterial partial pressure of oxygen (PaO2) at the treatment initiation for severe infection. Hyperoxia was defined as a PaO2 level of ≥300 mm Hg and in-hospital mortality was compared between patients with and without hyperoxia. RESULTS: Of the 563 patients eligible for the study, 49 had hyperoxia at treatment initiation for severe infection. The in-hospital all-cause mortality rates of patients with and without hyperoxia were 14 (29.2%) and 90 (17.6%), respectively. Inverse probability weighting analyses with propensity scores revealed the association between hyperoxia and increased in-hospital mortality rate (28.8% vs 18.8%; adjusted OR 1.75 (1.03 to 2.97); p=0.038), adjusting for patient demographics, comorbidities, site of infection, severity of infection, haemodynamic and respiratory status, laboratory data and location of patient at infection development. Acute lung injury developed more frequently in patients with hyperoxia on the following days after infection treatment, whereas sepsis-related mortality was comparable regardless of hyperoxia exposure. CONCLUSION: Hyperoxia with PaO2 ≥300 mm Hg at treatment initiation of severe infection was associated with an increased in-hospital mortality rate in patients requiring intensive care. The amount of oxygen to administer to patients with severe infection should be carefully determined. TRIAL REGISTRATION NUMBER: University Hospital Medical Information Network Clinical Trial Registry (UMIN000027452).

Precision engineered peptide targeting leukocyte extracellular traps mitigate acute kidney injury in Crush syndrome.

Crush syndrome induced by skeletal muscle compression causes fatal rhabdomyolysis-induced acute kidney injury (RIAKI) that requires intensive care, including hemodialysis. However, access to crucial medical supplies is highly limited while treating earthquake victims trapped under fallen buildings, lowering their chances of survival. Developing a compact, portable, and simple treatment method for RIAKI remains an important challenge. Based on our previous finding that RIAKI depends on leukocyte extracellular traps (ETs), we aimed to develop a novel medium-molecular-weight peptide to provide clinical treatment of Crush syndrome. We conducted a structure-activity relationship study to develop a new therapeutic peptide. Using human peripheral polymorphonuclear neutrophils, we identified a 12-amino acid peptide sequence (FK-12) that strongly inhibited neutrophil extracellular trap (NET) release in vitro and further modified it by alanine scanning to construct multiple peptide analogs that were screened for their NET inhibition ability. The clinical applicability and renal-protective effects of these analogs were evaluated in vivo using the rhabdomyolysis-induced AKI mouse model. One candidate drug [M10Hse(Me)], wherein the sulfur of Met10 is substituted by oxygen, exhibited excellent renal-protective effects and completely inhibited fatality in the RIAKI mouse model. Furthermore, we observed that both therapeutic and prophylactic administration of M10Hse(Me) markedly protected the renal function during the acute and chronic phases of RIAKI. In conclusion, we developed a novel medium-molecular-weight peptide that could potentially treat patients with rhabdomyolysis and protect their renal function, thereby increasing the survival rate of victims affected by Crush syndrome.

Early versus delayed vasopressor administration in patients with septic shock.

Aim: This study aimed to investigate the association of early vasopressor initiation with improved septic shock outcomes. Methods: This multicenter observational study was conducted in 17 intensive care units in Japan and included adult patients with sepsis admitted to the intensive care unit from July 2019 to August 2020 and treated with vasopressor therapy. Patients were divided into the early vasopressor group (≤1 h from sepsis recognition) and the delayed vasopressor group (>1 h). The impact of early vasopressor administration on risk-adjusted in-hospital mortality was estimated using logistic regression analyses adjusted by an inverse probability of treatment weighting analysis with propensity scoring. Results: Among the 97 patients, 67 received vasopressor therapy within 1 h from sepsis recognition and 30 received vasopressor after 1 h. In-hospital mortality was 32.8% in the early vasopressor group and 26.7% in the delayed vasopressor group (p = 0.543). The adjusted odds ratio for in-hospital mortality was 0.76 (95% confidence interval 0.17-3.29) when comparing patients in the early vasopressor with those in the delayed vasopressor group. The fit curve from the mixed-effects model showed a relatively lower trend toward an infusion volume over time in the early vasopressor group than in the delayed vasopressor group. Conclusion: Our study did not reach a definitive conclusion for early vasopressor administration. However, early vasopressor administration may help avoid volume overload in the long course of sepsis care.

Sepsis-related coagulopathy treatment based on the disseminated intravascular coagulation diagnostic criteria: a post-hoc analysis of a prospective multicenter observational study.

BACKGROUND: The development of disseminated intravascular coagulation (DIC) in patients with sepsis has been repeatedly confirmed as a factor associated with poor prognosis. Anticoagulant therapy has been expected to improve sepsis patient outcomes, whereas no randomized controlled trials have demonstrated the survival benefit of anticoagulant therapies in non-specific overall sepsis. Patient selection based on the component of "high disease severity" in addition to "sepsis with DIC" has recently proved important in identifying appropriate targets for anticoagulant therapy. The aims of this study were to characterize "severe" sepsis DIC patients and to identify the patient population benefiting from anticoagulant therapy. METHODS: This retrospective sub-analysis of a prospective multicenter study included 1,178 adult patients with severe sepsis from 59 intensive care units in Japan from January 2016 to March 2017. We examined the association of patient outcomes, including organ dysfunction and in-hospital mortality, with the DIC score and prothrombin time-international normalized ratio (PT-INR), one of the components of the DIC score, using multivariable regression models including the cross-product term between these indicators. Multivariate Cox proportional hazard regression analysis with non-linear restricted cubic spline including a three-way interaction term (anticoagulant therapy × the DIC score × PT-INR) was also performed. Anticoagulant therapy was defined as the administration of antithrombin, recombinant human thrombomodulin, or their combination. RESULTS: In total, we analyzed 1013 patients. The regression model showed that organ dysfunction and in-hospital mortality deteriorated with higher PT-INR values in the range of < 1.5 and that this trend was more pronounced with higher DIC scores. Three-way interaction analysis demonstrated that anticoagulant therapy was associated with better survival outcome in patients with a high DIC score and high PT-INR. Furthermore, we identified a DIC score ≥ 5 and PT-INR ≥ 1.5 as the clinical threshold for identification of optimal targets for anticoagulant therapy. CONCLUSIONS: The combined use of the DIC score and PT-INR helps in selecting the optimal patient population for anticoagulant therapy in sepsis-induced DIC. The results obtained from this study will provide valuable information regarding the study design of randomized controlled trials examining the effects of anticoagulant therapy for sepsis. TRIAL REGISTRATION: UMIN-CTR, UMIN000019742. Registered on November 16, 2015.

Guideline-based management of acute respiratory failure and acute respiratory distress syndrome.

Acute respiratory failure (ARF) is defined by acute and progressive hypoxemia caused by various cardiorespiratory or systemic diseases in previously healthy patients. Among ARF, acute respiratory distress syndrome (ARDS) is a serious condition with bilateral lung infiltration, which develops secondary to a variety of underlying conditions, diseases, or injuries. This review summarizes the current standard of care for ARF and ARDS based on current major guidelines in this field. When administering fluid in patients with ARF, particularly ARDS, restrictive strategies need to be considered in patients without shock or multiple organ dysfunction. Regarding oxygenation targets, avoiding excessive hyperoxemia and hypoxemia is probably a reasonable choice. As a result of the rapid spread and accumulation of evidence for high-flow nasal cannula oxygenation, it is now weakly recommended for the respiratory management of ARF in general and even for initial management of ARDS. Noninvasive positive pressure ventilation is also weakly recommended for the management of certain ARF conditions and as initial management of ARDS. Low tidal volume ventilation is now weakly recommended for all patients with ARF and strongly recommended for patients with ARDS. Limiting plateau pressure and high-level PEEP are weakly recommended for moderate-to-severe ARDS. Prone position ventilation with prolonged hours is weakly to strongly recommended for moderate-to-severe ARDS. In patients with COVID-19, ventilatory management is essentially the same as for ARF and ARDS, but awake prone positioning may be considered. In addition to standard care, treatment optimization and individualization, as well as the introduction of exploratory treatment, should be considered as appropriate. As a single pathogen, such as SARS-CoV-2, exhibits a wide variety of pathologies and lung dysfunction, ventilatory management for ARF and ARDS may be better tailored according to the respiratory physiologic status of individual patients rather than the causal or underlying diseases and conditions.

How do medical students learn in an online community diagnostics program?

BACKGROUND: The need to engage medical students in understanding the social and environmental determinants of health in disparate communities is increasing. However, previous reviews have noted the limited community diagnosis programs and program evaluation. Given the feasibility of the programs, it is expected to be widely available online. Therefore, this study used a realist approach to identify learning patterns through an online community diagnosis program, namely context (C), mechanism (M), and outcomes (O) patterns. METHODS: A 2-week general medicine clinical practice program was conducted for 4th- and 5th-year medical students at a medical university in Japan. The program included a one-hour zoom-based lecture, feedback for students on their presentations on community diagnosis, and a structural report on community diagnosis. We developed the program based on variation theory, which views discernment and variation in situations having time, space, and social dimensions as core learning. The students' reflections on their learning through the program were thematically analyzed through CMO perspectives. The realist approach used in the online diagnosis program evaluation allows us to explore, test, and refine what mechanisms work under what conditions (context) and with what interventions (including opportunities and resources), from which we can describe iteratively explainable results. RESULTS: First, the medical students, who spent most of their time in the limited residential areas they lived in, discovered the characteristics of their own community by discovery learning and comparison among peers. Second, they increased their intrinsic interest in the community by discerning specific issues in their familiar community through community diagnosis. Third, they valued community diagnosis by identifying relationships between local data on health issues under their learning responsibility. Fourth, they become more flexible in their thinking and created new knowledge that would fit the local community, and their reflection on themselves was encouraged. CONCLUSION: In this online community diagnosis program, medical students learned about the community through four types of learning patterns. Medical students may develop an understanding of community with interest using variation theory as a program development perspective and cognitive flexibility theory surrounding the essential ambiguity and abstraction of community.

An algorithm for PCT-guided antimicrobial therapy: a consensus statement by Japanese experts.

In Japan, a national antimicrobial resistance (AMR) action plan was adopted in 2016, advocating a 20% reduction in antibiotic consumption by 2020. However, there is still room for improvement to accomplish this goal. Many randomized controlled trials have reported that procalcitonin (PCT)-guided antimicrobial therapy could help to reduce antibiotic consumption without negative health effects, specifically in acute respiratory infections. In September 2018, some experts in Europe and the USA proposed algorithms for PCT-guided antimicrobial therapy in mild to moderate infection cases outside the ICU and severe cases in the ICU (the international experts consensus). Thereafter, a group of Japanese experts, including specialists in intensive care medicine, emergency medicine, respiratory medicine and infectious diseases, created a modified version of a PCT-guided algorithm (Japanese experts consensus). This modified algorithm was adapted to better fit Japanese medical circumstances, since PCT-guided therapy is not widely used in daily clinical practice in Japan. The Japanese algorithm has three specific characteristics. First, the target patients are limited to only hospitalized ICU or non-ICU patients. Second, pneumonia due to Pseudomonas aeruginosa, Staphylococcus aureus and Legionella species are excluded. Finally, a different timing of PCT follow-up measurement was proposed to meet restrictions of the Japanese medical insurance system. The adapted algorithms has high potential to further improve the safe reduction in antibiotic consumption in Japan, while reducing the spread of AMR pathogens.

Association of antithrombin with development of trauma-induced disseminated intravascular coagulation and outcomes.

Introduction: Trauma activates the innate immune system to modulate hemostasis and minimize the damage caused by physiological bodily responses, including the activation of coagulation. Sufficiently severe trauma overwhelms physiological responses and elicits the systemic inflammatory response syndrome, which leads to the onset of disseminated intravascular coagulation (DIC), characterized by dysregulated inflammatory coagulofibrinolytic responses. Impaired anticoagulant mechanisms, including antithrombin, constitutes the pathology of DIC, while the dynamics of antithrombin and relevance to outcomes in trauma-induced coagulopathy have not been fully elucidated. This study investigated the associations of antithrombin activity with DIC onset and outcomes in severely injured patients. Methods: This retrospective sub-analysis of a multicenter, prospective study included patients with an injury severity score ≥16. We characterized trauma patients with low antithrombin activity (antithrombin <80% on hospital arrival, n = 75) in comparison with those who had normal antithrombin activity (antithrombin ≥80%, n = 200). Global markers of coagulation and fibrinolysis, molecular biomarkers for thrombin generation (soluble fibrin [SF]), and markers of anticoagulation (antithrombin) were evaluated to confirm the associations of antithrombin with DIC development and outcomes, including in-hospital mortality and the multiple organ dysfunction syndrome (MODS). Results: Patients with low antithrombin activity had higher prevalence of shock, transfusion requirements, and in-hospital mortality. Higher DIC scores and more severe organ dysfunction were observed in the low AT group compared to that in the normal AT group. Antithrombin activity on arrival at the hospital was an independent predictor of the development of DIC in trauma patients, and levels of SF increased with lower antithrombin values (antithrombin activity > 85%). Antithrombin activity at 3 h showed good predictive performance for in-hospital mortality, and a multivariable Cox proportional-hazard regression model with a cross-product term between the antithrombin and DIC showed that the in-hospital mortality in patients with DIC increased with decreased antithrombin activity. A multivariable logistic regression model showed that the odds for the development of MODS in patients with DIC increased with lower antithrombin values. Conclusion: Decreased antithrombin activity in trauma-induced coagulopathy is associated with poor outcomes through worsening of DIC.

Effects of tranexamic acid on coagulofibrinolytic markers during the early stage of severe trauma: A propensity score-matched analysis.

Tranexamic acid (TXA) reduces the risk of bleeding trauma death without altering the need for blood transfusion. We examined the effects of TXA on coagulation and fibrinolysis dynamics and the volume of transfusion during the early stage of trauma. This subanalysis of a prospective multicenter study of severe trauma included 276 patients divided into propensity score-matched groups with and without TXA administration. The effects of TXA on coagulation and fibrinolysis markers immediately at (time point 0) and 3 hours after (time point 3) arrival at the emergency department were investigated. The transfusion volume was determined at 24 hours after admission. TXA was administered to the patients within 3 hours (median, 64 minutes) after injury. Significant reductions in fibrin/fibrinogen degradation products and D-dimer levels from time points 0 to 3 in the TXA group compared with the non-TXA group were confirmed, with no marked differences noted in the 24-hour transfusion volumes between the 2 groups. Continuously increased levels of soluble fibrin, a marker of thrombin generation, from time points 0 to 3 and high levels of plasminogen activator inhibitor-1, a marker of inhibition of fibrinolysis, at time point 3 were observed in both groups. TXA inhibited fibrin(ogen)olysis during the early stage of severe trauma, although this was not associated with a reduction in the transfusion volume. Other confounders affecting the dynamics of fibrinolysis and transfusion requirement need to be clarified.

Age-related differences in the survival benefit of the administration of antithrombin, recombinant human thrombomodulin, or their combination in sepsis.

Disseminated intravascular coagulation (DIC) is one of the major organ dysfunctions associated with sepsis. This retrospective secondary analysis comprised data from a prospective multicenter study to investigate the age-related differences in the survival benefit of anticoagulant therapy in sepsis according to the DIC diagnostic criteria. Adult patients with severe sepsis based on the Sepsis-2 criteria were enrolled and divided into the following groups: (1) anticoagulant group (patients who received anticoagulant therapy) and (2) non-anticoagulant group (patients who did not receive anticoagulant therapy). Patients in the former group were administered antithrombin, recombinant human thrombomodulin, or their combination. The increases in the risk of hospital mortality were suppressed in the high-DIC-score patients aged 60-70 years receiving anticoagulant therapy. No favorable association of anti-coagulant therapy with hospital mortality was observed in patients aged 50 years and 80 years. Furthermore, anticoagulant therapy in the lower-DIC-score range increased the risk of hospital mortality in patients aged 50-60 years. In conclusion, anticoagulant therapy was associated with decreased hospital mortality according to a higher DIC score in septic patients aged 60-70 years. Anticoagulant therapy, however, was not associated with a better outcome in relatively younger and older patients with sepsis.

Disparities in co-payments for influenza vaccine among the elderly, during the COVID-19 pandemic in Japan.

INTRODUCTION: Seasonal influenza vaccination for the elderly is highly recommended during the COVID-19 pandemic. In Japan, the amount of subsidy for influenza differs among municipalities. Thus, we investigated the amount of and variation in subsidy for influenza vaccination for the elderly in 2020. METHODS: This was an ecological study of 1,922 municipalities in Japan. The amount of subsidy for influenza vaccines for the elderly in each municipality was surveyed through websites or via telephone. Geographic and financial data for municipalities and prefectures were obtained from the open data. The amount of co-payment for the influenza vaccine and the geographical and financial status of each municipality were compared, according to the aging rate. Univariate logistic regression analysis was performed to explore factors related to the free influenza vaccine. RESULTS: Municipalities with higher aging rates tended to have higher median co-payments for vaccines in 2020. (0 yen vs 1000 yen, p < 0.001) In addition, they tended to have worse financial conditions and lower per capita incomes. A similar trend was observed in the analysis by prefecture, i.e., a higher influenza mortality rate in prefectures with a higher aging rate. Despite having lower incomes, municipalities and prefectures with higher aging populations had higher mortality rates from influenza and higher co-payments for influenza vaccination. CONCLUSIONS: In Japan, there is a disparity among elderly people; areas with an aging population have higher co-payments for influenza vaccines despite lower incomes, suggesting that the government needs to implement corrective measures to reduce this disparity.

Association between multimorbidity, self-rated health and life satisfaction among independent, community-dwelling very old persons in Japan: longitudinal cohort analysis from the Kawasaki Ageing and Well-being Project.

OBJECTIVE: This study aimed to identify associations between multimorbidity and subjective health outcomes among the very old persons, after adjusting for coexisting conditions such as frailty and depression. STUDY SETTING AND PARTICIPANTS: This was an observational cross-sectional study involving 1012 independent, community-dwelling very old persons (507 men, 505 women; aged 85-89 years) in Kawasaki city, Japan. OUTCOME MEASURES: The primary outcome was the cross-sectional associations between multimorbidity and poor self-rated health (SRH) and life satisfaction using binary logistic regression. The secondary outcome was the association of subjective health with each chronic condition. RESULTS: The prevalence of multimorbidity (≥2 conditions) was 94.7%, and the average number of chronic conditions was 4.47±1.9. Multimorbidity was significantly associated with poor SRH in the adjusted model only when six or more chronic conditions were present (OR 4.80; 95% CI 1.34 to 17.11; p=0.016). Cerebrovascular disease, heart disease, respiratory disease, connective tissue disease and arthritis showed significant associations with poor SRH after multivariate adjustment. Sex-specific analysis replicated associations between multimorbidity with six or more conditions and SRH in both men and women, while the diseases with the greatest impact on SRH differed between men and women. Most conditions were not associated with low satisfaction with life scale, with the exception of arthritis (OR 1.92, 95% CI 1.32 to 2.78, p=0.001). CONCLUSIONS: Multimorbidity is prevalent in the independent, community-dwelling very old persons and is associated with poor SRH when six or more conditions are present; conditions causing mobility limitations, such as cerebrovascular disease, connective tissue disease and arthritis, have a negative impact on SRH. TRIAL REGISTRATION NUMBER: UMIN000026053.

Nasal intubation for trauma patients and increased in-hospital mortality.

PURPOSE: Data regarding harm from nasal intubation in trauma patients have been conflicting. This study aims to elucidate whether nasal intubation is associated with increased in-hospital mortality compared with oral intubation. METHODS: A retrospective cohort study on a nationwide trauma registry of 2004-2019 was conducted. Adult trauma patients who underwent nasal or oral intubation during initial resuscitation were selected. In-hospital mortality and lung complications were compared between nasal and oral intubations. A generalized estimating equation model accounting for within-institution clustering was adopted. Patient demographics, comorbidities, mechanism, injury severity, and vital signs on hospital arrival were adjusted. Subgroup analyses were conducted based on age, Abbreviated Injury Scale [AIS] for the head and face, and vital signs on arrival. RESULTS: Among 29,271 patients eligible for the study, 667 were intubated nasally. In-hospital mortality was higher in nasal intubation compared with oral intubation (OR, 1.28 [95% CI, 1.01-1.64]). There were more noninfectious pulmonary complications in nasal intubation (OR, 1.48 [1.14-1.94]). The harms of nasal intubation were observed only in the elderly (age ≥ 75), patients with severe head injury (AIS in the head ≥ 4), and normotensive patients (systolic blood pressure ≥ 90 mmHg). Conversely, mortality was comparable regardless of the route of intubation in patients with complicated facial injury (AIS in the face ≥ 3). CONCLUSION: Nasal intubation was associated with increased in-hospital mortality, particularly in older patients and severe head injury, but not severe facial injury. The route of intubation should be judiciously decided during trauma resuscitation.

Pathophysiology of Coagulopathy Induced by Traumatic Brain Injury Is Identical to That of Disseminated Intravascular Coagulation With Hyperfibrinolysis.

Background: Traumatic brain injury (TBI)-associated coagulopathy is a widely recognized risk factor for secondary brain damage and contributes to poor clinical outcomes. Various theories, including disseminated intravascular coagulation (DIC), have been proposed regarding its pathomechanisms; no consensus has been reached thus far. This study aimed to elucidate the pathophysiology of TBI-induced coagulopathy by comparing coagulofibrinolytic changes in isolated TBI (iTBI) to those in non-TBI, to determine the associated factors, and identify the clinical significance of DIC diagnosis in patients with iTBI. Methods: This secondary multicenter, prospective study assessed patients with severe trauma. iTBI was defined as Abbreviated Injury Scale (AIS) scores ≥4 in the head and neck, and ≤2 in other body parts. Non-TBI was defined as AIS scores ≥4 in single body parts other than the head and neck, and the absence of AIS scores ≥3 in any other trauma-affected parts. Specific biomarkers for thrombin and plasmin generation, anticoagulation, and fibrinolysis inhibition were measured at the presentation to the emergency department (0 h) and 3 h after arrival. Results: We analyzed 34 iTBI and 40 non-TBI patients. Baseline characteristics, transfusion requirements and in-hospital mortality did not significantly differ between groups. The changes in coagulation/fibrinolysis-related biomarkers were similar. Lactate levels in the iTBI group positively correlated with DIC scores (rho = -0.441, p = 0.017), but not with blood pressure (rho = -0.098, p = 0.614). Multiple logistic regression analyses revealed that the injury severity score was an independent predictor of DIC development in patients with iTBI (odds ratio = 1.237, p = 0.018). Patients with iTBI were further subdivided into two groups: DIC (n = 15) and non-DIC (n = 19) groups. Marked thrombin and plasmin generation were observed in all patients with iTBI, especially those with DIC. Patients with iTBI and DIC had higher requirements for massive transfusion and emergency surgery, and higher in-hospital mortality than those without DIC. Furthermore, DIC development significantly correlated with poor hospital survival; DIC scores at 0 h were predictive of in-hospital mortality. Conclusions: Coagulofibrinolytic changes in iTBI and non-TBI patients were identical, and consistent with the pathophysiology of DIC. DIC diagnosis in the early phase of TBI is key in predicting the outcomes of severe TBI.

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2020 (J-SSCG 2020).

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2020 (J-SSCG 2020), a Japanese-specific set of clinical practice guidelines for sepsis and septic shock created as revised from J-SSCG 2016 jointly by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine, was first released in September 2020 and published in February 2021. An English-language version of these guidelines was created based on the contents of the original Japanese-language version. The purpose of this guideline is to assist medical staff in making appropriate decisions to improve the prognosis of patients undergoing treatment for sepsis and septic shock. We aimed to provide high-quality guidelines that are easy to use and understand for specialists, general clinicians, and multidisciplinary medical professionals. J-SSCG 2016 took up new subjects that were not present in SSCG 2016 (e.g., ICU-acquired weakness [ICU-AW], post-intensive care syndrome [PICS], and body temperature management). The J-SSCG 2020 covered a total of 22 areas with four additional new areas (patient- and family-centered care, sepsis treatment system, neuro-intensive treatment, and stress ulcers). A total of 118 important clinical issues (clinical questions, CQs) were extracted regardless of the presence or absence of evidence. These CQs also include those that have been given particular focus within Japan. This is a large-scale guideline covering multiple fields; thus, in addition to the 25 committee members, we had the participation and support of a total of 226 members who are professionals (physicians, nurses, physiotherapists, clinical engineers, and pharmacists) and medical workers with a history of sepsis or critical illness. The GRADE method was adopted for making recommendations, and the modified Delphi method was used to determine recommendations by voting from all committee members. As a result, 79 GRADE-based recommendations, 5 Good Practice Statements (GPS), 18 expert consensuses, 27 answers to background questions (BQs), and summaries of definitions and diagnosis of sepsis were created as responses to 118 CQs. We also incorporated visual information for each CQ according to the time course of treatment, and we will also distribute this as an app. The J-SSCG 2020 is expected to be widely used as a useful bedside guideline in the field of sepsis treatment both in Japan and overseas involving multiple disciplines.

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2020 (J-SSCG 2020).

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2020 (J-SSCG 2020), a Japanese-specific set of clinical practice guidelines for sepsis and septic shock created as revised from J-SSCG 2016 jointly by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine, was first released in September 2020 and published in February 2021. An English-language version of these guidelines was created based on the contents of the original Japanese-language version. The purpose of this guideline is to assist medical staff in making appropriate decisions to improve the prognosis of patients undergoing treatment for sepsis and septic shock. We aimed to provide high-quality guidelines that are easy to use and understand for specialists, general clinicians, and multidisciplinary medical professionals. J-SSCG 2016 took up new subjects that were not present in SSCG 2016 (e.g., ICU-acquired weakness [ICU-AW], post-intensive care syndrome [PICS], and body temperature management). The J-SSCG 2020 covered a total of 22 areas with four additional new areas (patient- and family-centered care, sepsis treatment system, neuro-intensive treatment, and stress ulcers). A total of 118 important clinical issues (clinical questions, CQs) were extracted regardless of the presence or absence of evidence. These CQs also include those that have been given particular focus within Japan. This is a large-scale guideline covering multiple fields; thus, in addition to the 25 committee members, we had the participation and support of a total of 226 members who are professionals (physicians, nurses, physiotherapists, clinical engineers, and pharmacists) and medical workers with a history of sepsis or critical illness. The GRADE method was adopted for making recommendations, and the modified Delphi method was used to determine recommendations by voting from all committee members.As a result, 79 GRADE-based recommendations, 5 Good Practice Statements (GPS), 18 expert consensuses, 27 answers to background questions (BQs), and summaries of definitions and diagnosis of sepsis were created as responses to 118 CQs. We also incorporated visual information for each CQ according to the time course of treatment, and we will also distribute this as an app. The J-SSCG 2020 is expected to be widely used as a useful bedside guideline in the field of sepsis treatment both in Japan and overseas involving multiple disciplines.

Quick sequential organ failure assessment score combined with other sepsis-related risk factors to predict in-hospital mortality: Post-hoc analysis of prospective multicenter study data.

This study aimed to assess the value of quick sequential organ failure assessment (qSOFA) combined with other risk factors in predicting in-hospital mortality in patients presenting to the emergency department with suspected infection. This post-hoc analysis of a prospective multicenter study dataset included 34 emergency departments across Japan (December 2017 to February 2018). We included adult patients (age ≥16 years) who presented to the emergency department with suspected infection. qSOFA was calculated and recorded by senior emergency physicians when they suspected an infection. Different types of sepsis-related risk factors (demographic, functional, and laboratory values) were chosen from prior studies. A logistic regression model was used to assess the predictive value of qSOFA for in-hospital mortality in models based on the following combination of predictors: 1) qSOFA-Only; 2) qSOFA+Age; 3) qSOFA+Clinical Frailty Scale (CFS); 4) qSOFA+Charlson Comorbidity Index (CCI); 5) qSOFA+lactate levels; 6) qSOFA+Age+CCI+CFS+lactate levels. We calculated the area under the receiver operating characteristic curve (AUC) and other key clinical statistics at Youden's index, where the sum of sensitivity and specificity is maximized. Following prior literature, an AUC >0.9 was deemed to indicate high accuracy; 0.7-0.9, moderate accuracy; 0.5-0.7, low accuracy; and 0.5, a chance result. Of the 951 patients included in the analysis, 151 (15.9%) died during hospitalization. The AUC for predicting in-hospital mortality was 0.627 (95% confidence interval [CI]: 0.580-0.673) for the qSOFA-Only model. Addition of other variables only marginally improved the model's AUC; the model that included all potentially relevant variables yielded an AUC of only 0.730 (95% CI: 0.687-0.774). Other key statistic values were similar among all models, with sensitivity and specificity of 0.55-0.65 and 0.60-0.75, respectively. In this post-hoc data analysis from a prospective multicenter study based in Japan, combining qSOFA with other sepsis-related risk factors only marginally improved the model's predictive value.

Association of frailty on treatment outcomes among patients with suspected infection treated at emergency departments.

BACKGROUND: The clinical frailty scale (CFS) score has been validated as a predictor of adverse outcomes in community-dwelling older people. Older people are at a higher risk of sepsis and have a higher mortality rate. However, the association of frailty on outcomes in patients with sepsis has not been completely examined. OBJECTIVE: This study evaluated the association between CFS and outcomes in patients with sepsis. DESIGN: This was a multicenter prospective cohort substudy. SETTINGS AND PARTICIPANTS: The study included 37 emergency departments from across Japan. The patients (age ≥16 years) were included in this study if they had suspected infection at an emergency department during December 2017-February 2018. OUTCOME MEASURE AND ANALYSIS: The primary outcome was 28-day mortality, stratified by the CFS score categories. The secondary outcomes were the duration of hospital stay, number of ICU-free days (ICUFDs) and number of ventilator-free days (VFDs). MAIN RESULTS: A total of 917 patients were included. The median age was 79 years. The CFS score was associated with an increased risk of 28-day mortality and with a higher likelihood of long-term hospital stay and short-term VFDs and ICUFDs. Multivariate logistic regression analysis indicated that the CFS score was a predictor of 28-day mortality [odds ratio (OR), 1.26; 95% confidence interval (CI), 1.11-1.42]. CONCLUSIONS: This study reported that in patients with suspected sepsis in the emergency department, frailty may be associated with poor prognosis and length of hospital stay.

Disseminated intravascular coagulation immediately after trauma predicts a poor prognosis in severely injured patients.

Trauma patients die from massive bleeding due to disseminated intravascular coagulation (DIC) with a fibrinolytic phenotype in the early phase, which transforms to DIC with a thrombotic phenotype in the late phase of trauma, contributing to the development of multiple organ dysfunction syndrome (MODS) and a consequently poor outcome. This is a sub-analysis of a multicenter prospective descriptive cross-sectional study on DIC to evaluate the effect of a DIC diagnosis on the survival probability and predictive performance of DIC scores for massive transfusion, MODS, and hospital death in severely injured trauma patients. A DIC diagnosis on admission was associated with a lower survival probability (Log Rank P < 0.001), higher frequency of massive transfusion and MODS and a higher mortality rate than no such diagnosis. The DIC scores at 0 and 3 h significantly predicted massive transfusion, MODS, and hospital death. Markers of thrombin and plasmin generation and fibrinolysis inhibition also showed a good predictive ability for these three items. In conclusion, a DIC diagnosis on admission was associated with a low survival probability. DIC scores obtained immediately after trauma predicted a poor prognosis of severely injured trauma patients.