Published papers

Purpose: Although early prediction of mortality is useful for the management of patients with colorectal perforations, no significant perioperative predictive factors have been identified. The purpose of this study was to identify useful prognostic factors for patients with colorectal perforation. Methods: This single-center retrospective study included consecutive patients undergoing emergency surgery for colorectal perforation from January 2012 to December 2019. The primary outcome was combined 30 day and in-hospital mortality. Patient- and disease-related factors obtained perioperatively were evaluated for mortality prediction. A scoring system was developed to enhance clinical utility. Results: Overall, 146 patients were included and 20 (14%) died after surgery. Multivariate logistic regression identified five predictive factors: age, hemodialysis, uncommon perforation etiology, plasma albumin level, and decreased platelet count. The area under the receiver operating curve for the scoring system using these parameters was 0.894 (95% CI 0.835–0.952). Patients at high-risk of mortality were classified by the proposed score with a sensitivity of 90.0% and negative predictive value of 98.0%. Conclusion: This study identified five perioperative factors significantly associated with mortality of patients with colorectal perforation. Although these parameters predict mortality of patients with colorectal perforation using a score with high discrimination, further study is required to confirm these findings.

Background Septic-associated disseminated intravascular coagulation (DIC) is heterogeneous regarding prognosis and responsiveness to anticoagulant therapy. Objectives To investigate the relationship between the timing of development and recovery of DIC, its prognosis, and the difference in response to anticoagulant therapy in sepsis-associated DIC patients. Methods This study was performed with a dataset from a multicenter nationwide retrospective cohort study (J-Septic DIC registry) in Japan between 2011 and 2013 to reveal the subgroup "high risk of death in DIC"and investigate the relationship between anticoagulant use and mortality. Patients were assigned to four groups based on the International Society on Thrombosis and Haemostasis-overt DIC status at days 1 and 3: non-DIC (-/-), early-recovered DIC (+/-), late-onset DIC (-/+), and persistent DIC (+/+). Results A total of 1,922 patients were included. In-hospitalmortality in persistent and late-onset DIC patients was significantly higher than in patients with non-DIC and earlyrecovered DIC. This finding indicates that persistent DIC and late-onset DICwere a poorprognosis subgroup, "high-risk"DIC. Meanwhile, patients with high-risk DIC treated with anticoagulants had significantly better outcomes than those without anticoagulants after adjusting for confounding factors. Conclusion This study showed that individuals with a high risk of death, persistent DIC, and late-onset DIC were a poor-prognostic subgroup in septic DIC; however, highrisk DIC is also a subgroup that can obtain more benefits from anticoagulant therapy.

BACKGROUND The benefits of physician-staffed emergency medical services (EMS) for trauma patients remain unclear because of the conflicting results on survival. Some studies suggested potential delays in definitive hemostasis due to prolonged prehospital stay when physicians are dispatched to the scene. We examined hypotensive trauma patients who were transported by ambulance, with the hypothesis that physician-staffed ambulances would be associated with increased in-hospital mortality, compared with EMS personnel-staffed ambulances. METHODS A retrospective cohort study that included hypotensive trauma patients (systolic blood pressure ≤ 90 mm Hg at the scene) transported by ambulance was conducted using the Japan Trauma Data Bank (2004-2019). Physician-staffed ambulances are capable of resuscitative procedures, such as thoracotomy and surgical airway management, while EMS personnel-staffed ambulances could only provide advanced life support. In-hospital mortality and prehospital time until the hospital arrival were compared between patients who were classified based on the type of ambulance. Inverse probability weighting was conducted to adjust baseline characteristics including age, sex, comorbidities, mechanism of injury, vital signs at the scene, injury severity, and ambulance dispatch time. RESULTS Among 14,652 patients eligible for the study, 738 were transported by a physician-staffed ambulance. In-hospital mortality was higher in the physician-staffed ambulance than in the EMS personnel-staffed ambulance (201/699 [28.8%] vs. 2287/13,090 [17.5%]; odds ratio, 1.90 [1.61-2.26]; adjusted odds ratio, 1.22 [1.14-1.30]; p < 0.01), and the physician-staffed ambulance showed longer prehospital time (50 [36-66] vs. 37 [29-48] min, difference = 12 [11-12] min, p < 0.01). Such potential harm of the physician-staffed ambulance was only observed among patients who arrived at the hospital with persistent hypotension (systolic blood pressure < 90 mm Hg on hospital arrival) in subgroup analyses. CONCLUSION Physician-staffed ambulances were associated with prolonged prehospital stay and increased in-hospital mortality among hypotensive trauma patients compared with EMS personnel-staffed ambulance. LEVEL OF EVIDENCE Therapeutic, level IV.

Emergency department thoracotomy (EDT) was incorporated into traumatic out-of-hospital cardiac arrest (t-OHCA) resuscitation. Although current guidelines recommend EDT with survival predictors, futility following EDT has been demonstrated and the potential risks have not been thoroughly investigated. This study aimed to elucidate the benefits and harms of EDT for persistent cardiac arrest following injury until hospital arrival. This retrospective cohort study used a nationwide trauma registry (2019–2021) and included adult patients with t-OHCA both at the scene and on hospital arrival. Survival to discharge, hemostatic procedure frequency, and transfusion amount were compared between patients treated with and without EDT. Inverse probability weighting using a propensity score was conducted to adjust age, sex, comorbidities, mechanism of injury, prehospital resuscitative procedure, prehospital physician presence, presence of signs of life, degree of thoracic injury, transportation time, and institutional characteristics. Among 1289 patients, 374 underwent EDT. The longest transportation time for survivors was 8 and 23 min in patients with and without EDT, respectively. EDT was associated with lower survival to discharge (4/374 [1.1%] vs. 22/915 [2.4%]; adjusted odds ratio [OR], 0.43 [95% CI 0.22–0.84]; p = 0.011), although patients with EDT underwent more frequent hemostatic surgeries (46.0% vs. 5.0%; adjusted OR, 16.39 [95% CI 12.50–21.74]) and received a higher amount of transfusion. Subgroup analyses revealed no association between EDT and lower survival in patients with severe chest injuries (1.0% vs. 1.4%; adjusted OR, 0.72 [95% CI 0.28–1.84]). EDT was associated with lower survival till discharge in trauma patients with persistent cardiac arrests after adjusting for various patient backgrounds, including known indications for EDT. The idea that EDT is the last resort for t-OHCA should be reconsidered and EDT indications need to be deliberately determined. Trial registration This study is retrospectively registered at University Hospital Medical Information Network (UMIN ID: UMIN000050840).

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.

This study aimed to identify prognostic factors for severe sepsis-related in-hospital mortality using the structural equation model (SEM) analysis with statistical causality. Sepsis data from the Focused Outcomes Research in Emergency Care in Acute Respiratory Distress Syndrome, Sepsis, and Trauma study (FORECAST), a multicenter cohort study, was used. Forty seven observed variables from the database were used to construct 4 latent variables. SEM analysis was performed on these latent variables to analyze the statistical causality among these data. This study evaluated whether the variables had an effect on in-hospital mortality. Overall, 1148 patients were enrolled. The SEM analysis showed that the 72-hour physical condition was the strongest latent variable affecting mortality, followed by physical condition before treatment. Furthermore, the 72-hour physical condition and the physical condition before treatment strongly influenced the Sequential Organ Failure Assessment (SOFA) score with path coefficients of 0.954 and 0.845, respectively. The SOFA score was the strongest variable that affected mortality after the onset of severe sepsis. The score remains the most robust prognostic factor and can facilitate appropriate policy development on care.

Background Patients with traumatic out-of-hospital cardiac arrest (t-OHCA) require on-scene airway management to maintain tissue oxygenation. However, the benefits of prehospital endotracheal intubation remain unclear, particularly regarding neurological outcomes. Therefore, this study aimed to evaluate the association between prehospital intubation and favourable neurological outcomes in patients with t-OHCA. Methods This retrospective cohort study used a Japanese nationwide trauma registry from 2019 to 2021. It included adult patients diagnosed with traumatic cardiac arrest on emergency medical service arrival. Glasgow Outcome Scale (GOS) scores, survival at discharge and presence of signs of life on hospital arrival were compared between patients with prehospital intubation and those with supraglottic airway or manual airway management. Inverse probability weighting with propensity scores was used to adjust for patient, injury, treatment and institutional characteristics, and the effects of intubation on outcomes averaged over baseline covariates were shown as marginal ORs. Results A total of 1524 patients were included in this study, with 370 undergoing intubation before hospital arrival. Prehospital intubation was associated with favourable neurological outcomes at discharge (GOS≥4 in 5/362 (1.4%) vs 10/1129 (0.9%); marginal OR 1.99; 95% CI 1.12 to 3.53; p=0.021) and higher survival to discharge (25/370 (6.8%) vs 63/1154 (5.5%); marginal OR 1.43; 95% CI 1.08 to 1.90; p=0.012). However, no association with signs of life on hospital arrival was observed (65/341 (19.1%) vs 147/1026 (14.3%); marginal OR 1.09; 95% CI 0.89 to 1.34). Favourable outcomes were observed only in patients who underwent intubation with a severe chest injury (Abbreviated Injury Score ≥3) and with transportation time to hospital >15 min (OR 14.44 and 2.00; 95% CI 1.89 to 110.02 and 1.09 to 3.65, respectively). Conclusions Prehospital intubation was associated with favourable neurological outcomes among adult patients with t-OHCA who had severe chest injury or transportation time >15 min.

A limited number of studies have investigated the association between short-term exposure to PM2.5components and morbidity. The present case-crossover study explored the association between exposure to total PM2.5and its components and emergency ambulance dispatches, which is one of the indicators of morbidity, in the 23 Tokyo wards. Between 2016 and 2018 (mean mass concentrations of total PM2.513.5 μg/m3), we obtained data, from the Tokyo Fire Department, on the daily cases of ambulance dispatches. Fine particles were collected at a fixed monitoring site and were analyzed to estimate the daily mean concentrations of carbons and ions. We analyzed 1038301 cases of health-based all-cause ambulance dispatches by using a conditional logistic regression model. The average concentrations of total PM2.5over one and the previous day were positively associated with the number of ambulance dispatches. In terms of PM2.5components, the percentage increase per interquartile range (IQR) increase was 0.8% for elemental carbon (IQR = 0.8 μg/m395% CI = 0.3-1.3%), 0.9% for sulfate (2.1 μg/m30.5-1.4%), and 1.1% for ammonium (1.3 μg/m30.4-1.8%) in the PM2.5-adjusted models. This is the first study to find an association between some specific components in PM2.5and ambulance dispatches.

Background: Starting infusion at a rate based on the Baxter formula is the global standard. However, with this infusion formula, an excessive amount of fluid may be stored inside the body (fluid creep), which may lead to severe respiratory disorders or abdominal compartment syndrome. The present study explored whether the Baxter formula or the Modified Brooke formula is more beneficial for resuscitation in extensively burned patients. Methods: The study design was a randomized controlled trial. One group received conventional intervention based on the Baxter formula, and the other received intervention using the infusion method by the Modified Brooke formula. Thirty-nine patients were enrolled in this study by admission to each hospital for 3 years. Of the 39 cases, 3 dropped out according to the study protocol, so 36 cases were analyzed, and 17 patients in the Modified Brooke formula group and 19 in the Baxter formula group were used for the analyses in this study. Results: There were no statistically significant differences between the 2 groups in the age, gender, body weight, burn severity, infusion volume required within 2 days after admission, serum creatinine, and acute kidney injury based on the KDIGO guideline within 48 h after arrival at the hospital, daily P/F ratio within 1 week after hospitalization, survival rate on the 28th day, and discharge survival rate. There were no cases of abdominal compartment syndrome during the observation period. The Modified Brooke formula group failed to achieve the target urine output corresponding to the infusion volume within 8 h after arrival, especially in ≥40% TBSA burn patients, but it did not become a clinical problem. Conclusion: We were unable to conclusively demonstrate that the Modified Brooke formula blocked the occurrence of “fluid creep” in extensively burned patients. However, it was suggested that starting the initial resuscitation at half the conventional volume might contribute to an improved physiological condition in the acute phase of major burns.

Background: The effect of the surgical sealant AQUABRID on outcomes after acute aortic dissection repair has not been evaluated. The objective of this study was to examine whether the use of AQUABRID affects the volume of intraoperative blood transfusion or operative time in patients undergoing emergency surgery to repair acute aortic dissection. Methods: A multicenter retrospective cohort study from January 2007 to December 2021. A total of 399 patients underwent emergency acute aortic dissection repair. Propensity score matching was used to adjust for the type of surgery and other patient characteristics. Results: A total of 387 of the eligible 399 patients were included in this study and propensity score matching yielded 94 patients for whom characteristics were not significantly different between the two groups. The type of surgery was exactly matched (ascending aorta replacement: 19 [40%]; partial arch replacement: 13 [28%]; total arch replacement: 15 [32%] in each group). Within the matched cohort, there was a statistically significant difference in the volume of intraoperative blood transfusion. (AQUABRID vs. control: 34 [26–38] vs. 50 [38–60] U in Japan, p =.03). Operating time was significantly shorter in the AQUABRID group (total operation: mean ± SD, 343 ± 92 vs. 402 ± 161 min, p =.03; reconstruction for arch vessels: 29 ± 17 vs. 56 ± 22, p <.01). The rate of postoperative complications was comparable in the two groups. Failure to use AQUABRID was a significant predictor of the need for massive transfusion (>40 U) (odds ratio: 7.20; 95% confidence interval: 2.56–20.23; p <.01). Conclusions: The use of AQUABRID during emergency acute aortic dissection repair significantly decreased the volume of intraoperative blood transfusion and the duration of surgery.

Introduction: A nationwide survey was conducted to elucidate the current status and challenges of post-COVID-19 condition (PCC) management in Japanese medical institutions with infectious disease specialists, as PCC remains a significant health concern about accumulating knowledge regarding its impact on quality of life. Materials and methods: Between January 18 and March 9, 2024, a web-based survey comprising up to 24 questions was administered to 880 infectious disease specialists nationwide. The survey investigated respondents' attributes and backgrounds, management experience, patient characteristics, treatment status, and PCC conditions among medical staff. Results: Responses were obtained from 465 specialists across 47 prefectures (52.8 % response rate). Among the 324 hospital-affiliated respondents, 69.7 % had experience in managing PCC, whereas only 11.2 % had dedicated specialized outpatient clinics. Most respondents reported that PCC was predominantly observed in the 18–64 age group, with 80.5 % and 51.9 % of the respondents reporting patients with symptoms lasting over 3 and 12 months, respectively. In patients with symptoms persisting over 3 months, many respondents noted that neuropsychiatric manifestations including depression and forgetfulness were common. Treatment approaches included pharmacotherapy, rehabilitation, and counseling. Additionally, 27.4 % of institutions reported PCC cases among staff, with two-thirds requiring work leave. Conclusion: Although many medical institutions with infectious disease specialists provide COVID-19 treatment, the establishment of specialized PCC outpatient clinics remains limited. This highlights the need for comprehensive long-term follow-up and support systems, particularly for healthcare workers affected by PCC, emphasizing the importance for developing effective return-to-work support systems.

Objectives: Several inflammation markers have been reported to be associated with unfavorable clinical outcomes in critically ill patients. We aimed to elucidate whether serum interleukin-6 concentration considered with Sequential Organ Failure Assessment score can better predict mortality in critically ill patients. Design: A prospective observational study. Setting: Five university hospitals in 2016-2018. Patients: Critically ill adult patients who met greater than or equal to two systemic inflammatory response syndrome criteria at admission were included, and those who died or were discharged within 48 hours were excluded. Interventions: Inflammatory biomarkers including interleukin (interleukin)-6, -8, and -10; tumor necrosis factor-α; C-reactive protein; and procalcitonin were blindly measured daily for 3 days. Area under the receiver operating characteristic curve for Sequential Organ Failure Assessment score at day 2 according to 28-day mortality was calculated as baseline. Combination models of Sequential Organ Failure Assessment score and additional biomarkers were developed using logistic regression, and area under the receiver operating characteristic curve calculated in each model was compared with the baseline. Measurements and Main Results: Among 161 patients included in the study, 18 (11.2%) did not survive at day 28. Univariate analysis for each biomarker identified that the interleukin-6 (days 1-3), interleukin-8 (days 0-3), and interleukin-10 (days 1-3) were higher in nonsurvivors than in survivors. Analyses of 28-day mortality prediction by a single biomarker showed interleukin-6, -8, and -10 at days 1-3 had a significant discrimination power, and the interleukin-6 at day 3 had the highest area under the receiver operating characteristic curve (0.766 [0.656-0.876]). The baseline area under the receiver operating characteristic curve for Sequential Organ Failure Assessment score predicting 28-day mortality was 0.776 (0.672-0.880). The combination model using additional interleukin-6 at day 3 had higher area under the receiver operating characteristic curve than baseline (area under the receiver operating characteristic curve = 0.844, area under the receiver operating characteristic curve improvement = 0.068 [0.002-0.133]), whereas other biomarkers did not improve accuracy in predicting 28-day mortality. Conclusions: Accuracy for 28-day mortality prediction was improved by adding serum interleukin-6 concentration to Sequential Organ Failure Assessment score.

Purpose: The incidence of invasive Group A Streptococcus (iGAS) infection and streptococcal toxic shock syndrome (STSS) is increasing. Early detection and diagnosis of cases that may progress to STSS are currently difficult. In this study, we aimed to identify biomarkers and emm type, one of the virulence factors, associated with STSS development. Methods: In this multicentre observational study including patients with iGAS infection (n = 305), we investigated the relative associations of host factors, clinical manifestations, biomarkers, and emm type with STSS. Results: The overall mortality rate was 15.4%; the fatality rate within 28 days of admission was higher in patients with STSS (67.9%, 38/56) than in those without (3.6%, 9/249). The most predominant type was emm1 (38%), detected in 73.2% of the patients with STSS. Risk factors for STSS identified by multivariable analysis included underlying kidney disease (odds ratio [OR], 10.7; 95% confidence interval [CI], 2.1–54.0, p = 0.004), bacteraemia without primary focus (OR, 3.6; 95% CI 1.2–11.1, p = 0.023), necrotizing fasciitis (OR, 8.7; 95% CI 2.6–29.4, p < 0.001), white blood cell count (WBC) < 4,000/µL (OR, 7.8; 95% CI 2.4–25.6, p = 0.001), serum creatine kinase (CK) ≥ 300 U/L (OR, 7.5; 95% CI 2.8–19.8, p < 0.001), and emm1 (OR, 5.2; 95% CI 2.0–13.4, p = 0.001). Conclusion: WBC < 4,000/µL and CK level ≥ 300 U/L on admission are additional relevant biomarkers for STSS prediction. The most predominant iGAS type, emm1, was significantly associated with STSS.

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.

Background: The effect of antithrombotic drugs on intraoperative operative blood loss volume in patients undergoing emergency surgery for generalized peritonitis is not well defined. The purpose of this study was to investigate the effect of antithrombotic drugs on intraoperative blood loss in patients with generalized peritonitis using a nationwide surgical registry in Japan. Method: This retrospective cohort study used a nationwide surgical registry data from 2011 to 2017 in Japan. Propensity score matching for the use of antithrombotic drugs was used for the adjustment of age, gender, comorbidities, frailty, preoperative state, types of surgery, surgical approach, laboratory data, and others. The main outcome was intraoperative blood loss: comparison of intraoperative blood loss, ratio of intraoperative blood loss after adjusted for confounding factors, and variable importance of all covariates. Results: A total of 70,105 of the eligible 75,666 patients were included in this study, and 2947 patients were taking antithrombotic drugs. Propensity score matching yielded 2864 well-balanced pairs. The blood loss volume was slightly higher in the antithrombotic drug group (100 [10–349] vs 70 [10–299] ml). After adjustment for confounding factors, the use of antithrombotic drugs was related to a 1.30-fold increase in intraoperative blood loss compared to non-use of antithrombotic drugs (95% CI, 1.16–1.45). The variable importance revealed that the effect of the use of antithrombotic drugs was minimal compared with surgical approach or type of surgery. Conclusion: This study shows that while taking antithrombotic drugs is associated with a slight increase in intraoperative blood loss in patients undergoing emergency surgery for generalized peritonitis, the effect is likely of minimal clinical significance.

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.

Background: The role of lactate level in selecting the timing of definitive surgery for isolated extremity fracture remains unclear. Therefore, we aimed to elucidate the use of preoperative lactate level for predicting early postoperative complications. Methods: This was a single-center retrospective observational study of patients with isolated extremity fracture who underwent orthopedic surgery. Patients who underwent lactate level assessment within 24 h prior to surgery were included. The incidence of early postoperative complications was compared between patients with a preoperative lactate level of ≥ 2 and < 2 mmol/L. Moreover, subgroup analyses were performed based on the time from hospital arrival to surgery and fracture type. Results: In total, 187 patients were included in the study. The incidence of postoperative complications was significantly higher in patients with a preoperative lactate level of ≥ 2 mmol/L than those with a preoperative lactate level of < 2 mmol/L. This result did not change after adjusting for age and severity. Further, a high preoperative lactate level was associated with a greater incidence of postoperative complications in patients who underwent definitive surgery within 6 h after arrival. Conclusion: A preoperative lactate level of ≥ 2 mmol/L was associated with a greater incidence of early postoperative complications in isolated extremity fractures. Nevertheless, this correlation was only observed among patients who underwent definitive fixation within 6 h after hospital arrival.

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.

Aberrant immune responses to viral pathogens contribute to pathogenesis, but our understanding of pathological immune responses caused by viruses within the human virome, especially at a population scale, remains limited. We analyzed whole-genome sequencing datasets of 6,321 Japanese individuals, including patients with autoimmune diseases (psoriasis vulgaris, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), pulmonary alveolar proteinosis (PAP) or multiple sclerosis) and coronavirus disease 2019 (COVID-19), or healthy controls. We systematically quantified two constituents of the blood DNA virome, endogenous HHV-6 (eHHV-6) and anellovirus. Participants with eHHV-6B had higher risks of SLE and PAP; the former was validated in All of Us. eHHV-6B-positivity and high SLE disease activity index scores had strong correlations. Genome-wide association study and long-read sequencing mapped the integration of the HHV-6B genome to a locus on chromosome 22q. Epitope mapping and single-cell RNA sequencing revealed distinctive immune induction by eHHV-6B in patients with SLE. In addition, high anellovirus load correlated strongly with SLE, RA and COVID-19 status. Our analyses unveil relationships between the human virome and autoimmune and infectious diseases.