Gp130-HIF1α axis-induced vascular damage is prevented by the short-term inhibition of IL-6 receptor signaling.

Protection against endothelial damage is recognized as a frontline approach to preventing the progression of cytokine release syndrome (CRS). Accumulating evidence has demonstrated that interleukin-6 (IL-6) promotes vascular endothelial damage during CRS, although the molecular mechanisms remain to be fully elucidated. Targeting IL-6 receptor signaling delays CRS progression; however, current options are limited by persistent inhibition of the immune system. Here, we show that endothelial IL-6 trans-signaling promoted vascular damage and inflammatory responses via hypoxia-inducible factor-1α (HIF1α)-induced glycolysis. Using pharmacological inhibitors targeting HIF1α activity or mice with the genetic ablation of gp130 in the endothelium, we found that inhibition of IL-6R (IL-6 receptor)-HIF1α signaling in endothelial cells protected against vascular injury caused by septic damage and provided survival benefit in a mouse model of sepsis. In addition, we developed a short half-life anti-IL-6R antibody (silent anti-IL-6R antibody) and found that it was highly effective at augmenting survival for sepsis and severe burn by strengthening the endothelial glycocalyx and reducing cytokine storm, and vascular leakage. Together, our data advance the role of endothelial IL-6 trans-signaling in the progression of CRS and indicate a potential therapeutic approach for burns and sepsis.

Association between tranexamic acid administration and mortality based on the trauma phenotype: a retrospective analysis of a nationwide trauma registry in Japan.

BACKGROUND: In trauma systems, criteria for individualised and optimised administration of tranexamic acid (TXA), an antifibrinolytic, are yet to be established. This study used nationwide cohort data from Japan to evaluate the association between TXA and in-hospital mortality among all patients with blunt trauma based on clinical phenotypes (trauma phenotypes). METHODS: A retrospective analysis was conducted using data from the Japan Trauma Data Bank (JTDB) spanning 2019 to 2021. RESULTS: Of 80,463 patients with trauma registered in the JTDB, 53,703 met the inclusion criteria, and 8046 (15.0%) received TXA treatment. The patients were categorised into eight trauma phenotypes. After adjusting with inverse probability treatment weighting, in-hospital mortality of the following trauma phenotypes significantly reduced with TXA administration: trauma phenotype 1 (odds ratio [OR] 0.68 [95% confidence interval [CI] 0.57-0.81]), trauma phenotype 2 (OR 0.73 [0.66-0.81]), trauma phenotype 6 (OR 0.52 [0.39-0.70]), and trauma phenotype 8 (OR 0.67 [0.60-0.75]). Conversely, trauma phenotypes 3 (OR 2.62 [1.98-3.47]) and 4 (OR 1.39 [1.11-1.74]) exhibited a significant increase in in-hospital mortality. CONCLUSIONS: This is the first study to evaluate the association between TXA administration and survival outcomes based on clinical phenotypes. We found an association between trauma phenotypes and in-hospital mortality, indicating that treatment with TXA could potentially influence this relationship. Further studies are needed to assess the usefulness of these phenotypes.

Impact of Coronavirus Disease 2019 (COVID-19) Outbreak on Emergency Patients Hospitalized With Cardiocerebrovascular Diseases in Osaka Prefecture, Japan　- A Population-Based Study.

BACKGROUND: Little is known about the transport and outcomes of emergency patients with cardiocerebrovascular diseases in Japan before and during the COVID-19 pandemic.Methods and Results: Data were extracted from a population-based registry in Osaka, Japan, from 2019 to 2021. There were almost no differences in the numbers of emergency patients hospitalized with myocardial infarction, stroke, or heart failure or their deaths. However, the number of cases of difficulty obtaining patient acceptance by hospitals increased in 2020 and 2021 compared with 2019. CONCLUSIONS: The numbers of emergency patients hospitalized with cardiocerebrovascular diseases and their deaths in Osaka were not affected by the COVID-19 epidemic.

Sex disparities in prehospital advanced cardiac life support in out-of-hospital cardiac arrests in Japan.

OBJECTIVE: Sex disparities in out-of-hospital cardiac arrest (OHCA) care processes have been reported. This study aimed to investigate the association between sex and prehospital advanced cardiac life support (ACLS) interventions provided by emergency medical services in Japan. METHODS: We analyzed data from January 1, 2013, to December 31, 2020, from the All-Japan Utstein Registry of patients with OHCA aged ≥18 years who were resuscitated by bystanders. The primary outcomes were prehospital ACLS interventions, including advanced airway management (AAM) and epinephrine administration. Sex-based disparities in receiving prehospital ACLS interventions were assessed via multivariable logistic regression analyses. RESULTS: Among 314,460 eligible patients, females with OHCA received fewer prehospital ACLS interventions than males: 83,571/187,834 (44.5%) males vs. 55,086/126,626 (43.5%) females (adjusted odds ratio [AOR] = 0.94, 95% confidence interval [CI] = 0.93-0.96) for AAM and 60,097/187,834 (32.0%) males vs. 35,501/126,626 (28.0%) females (AOR = 0.84, 95% CI = 0.83-0.85) for epinephrine administration. Similar results were also obtained in the subgroup analysis (groups included patients aged 18-74 years and ≥75 years and those with cardiac origin, ventricular fibrillation (VF), non-VF, non-family member witnessed, and family member witnessed). CONCLUSION: Compared with males, females were less likely to receive prehospital ACLS. Emergency medical service staff must be made aware of this disparity, and off-the-job training on intravenous cannulation or AAM replacement must be conducted. Investigation of the impact of sex disparity on OHCA care processes can facilitate planning of future public health policies to improve survival outcomes.

ABCD approach at the #7119 center, telephone triage system in Tokyo, Japan; a retrospective cohort study.

BACKGROUND: The algorithm and protocol of the #7119 telephone triage in Tokyo, Japan, had been originally established and consists of three steps. In this study, we investigated the outcome of patients treated with physiological abnormality (ABCD approach: A, airway; B, breathing; C, circulation, and D, dysfunction of central nervous system) in step 2 during the #7119 telephone triage and clarified the meaning of evaluation of this approach. METHODS: We retrospectively reviewed data from the Tokyo Fire Department from January 2016 to December 2017. Almost all the patients triaged using the ABCD approach were transferred to the hospital by ambulance and assigned severity by a physician. We divided patients into groups with combinations of 15 patterns including A, B, C, D, AB, AC, AD, BC, BD, CD, ABC, ABD, ACD, BCD, and ABCD. We compared the proportion of severe cases in each group using a Fisher's exact test, followed by residual analysis. RESULTS: We analyzed 13,793 cases triaged using the ABCD approach. In this analysis, 31% of total cases were assessed as severe cases. Groupwise analysis showed that the proportion of severe cases was significantly higher in the AD, BC, CD, ABD, and ABCD groups, while it was significantly less in the C and AB groups than in the total cases. CONCLUSION: At the #7119 telephone triage, we can pick up the severe cases by the ABCD approach. This may contribute to the prompt transportation of severe patients to hospitals by dispatching ambulance cars using the #7119 telephone triage methods.

[THE ANALYSIS OF ANAPHYLAXIS DIAGNOSED AT DERMATOLOGY OF TOKYO MEDICAL UNIVERSITY HOSPITAL].

OBJECTIVE: There are few epidemiological reports of anaphylaxis since childhood. We herein examined cases of anaphylaxis diagnosed in our department. METHODS: One hundred-thirty-two patients who were examined at the Dermatology Department of Tokyo Medical University Hospital between January 2011 and March 2017 and were prescribed epinephrine autoinjector (EpiPen®) for treatment were enrolled. The referral institution if any, severity of anaphylaxis, diagnostic method, causative antigen, and recurrence rate was examined. RESULTS: The referral rate was 54% while 46% of patients requested examination of their own accord. Anaphylaxis severity was mild to moderate in 75% of cases. Food allergy accounted for 71% of the symptoms, with wheat as the most common causative antigen, followed by Anisakis allergy. After diagnosis only 37% of patients continued periodic consultations, and 16 patients recurred anaphylaxis of the diagnosis. CONCLUSION: Wheat and WDEIA were the most frequent causes of anaphylaxis diagnosed in our department. We also found that as many as 15% of patients had Anisakis allergy, suggesting that it may be an important item in antigen testing.

Analysis of comprehensive biomolecules in critically ill patients via bioinformatics technologies.

Each patient with a critical illness such as sepsis and severe trauma has a different genetic background, comorbidities, age, and sex. Moreover, pathophysiology changes dynamically over time even in the same patient. Therefore, individualized treatment is necessary to account for heterogeneity in patient backgrounds. Recently, the analysis of comprehensive biomolecular information using clinical specimens has revealed novel molecular pathological classifications called subtypes. In addition, comprehensive biomolecular information using clinical specimens has enabled reverse translational research, which is a data-driven approach to the identification of drug target molecules. The development of these methods is expected to visualize the heterogeneity of patient backgrounds and lead to personalized therapy.

Association between lung contusion volume and acute changes in fibrinogen levels: A single-center observational study.

Aim: Organ tissue damage, including the lungs, may lead to acute coagulopathy. This study aimed to evaluate the association between lung contusion volume and serum fibrinogen level during the acute phase of trauma. Methods: We conducted an observational study using electronic medical records at a tertiary-care center between January 2015 and December 2018. We included patients with lung contusions on hospital arrival. We used three-dimensional computed tomography to calculate lung contusion volumes. The primary outcome was the lowest fibrinogen level measured within 24 h of hospital arrival. We evaluated the association between lung contusion volume and outcome with multivariable linear regression analysis. Also, we calculated the sensitivity and specificity of lung contusion volume in patients with a serum fibrinogen level of ≤150 mg/dL. Results: We identified 124 eligible patients. Their median age was 43.5 years, and 101 were male (81.5%). The median lung contusion volume was 10.9%. The median lowest fibrinogen level within 24 h from arrival was 188.0 mg/dL. After adjustment, lung contusion volume had a statistically significant association with the lowest fibrinogen level within 24 h from arrival (coefficient -1.6, 95% confidence interval -3.16 to -0.07). When a lung contusion volume of 20% was used as the cutoff, the sensitivity and specificity to identify fibrinogen depletion were 0.27 and 0.95, respectively. Conclusion: Lung contusion volume was associated with the lowest fibrinogen level measured within 24 h from hospital arrival. Measuring lung contusion volume may help to identify patients with a progression of fibrinogen depletion.

The timing of death in burn patients.

Aim: When treating burn patients, some patients die in the chronic phase, even if they overcome the acute phase of the burn. To elucidate the timing of death and its underlying causes among burn patients. Methods: Patients evaluated were admitted to our burn center between January 2015, and December 2019. Patient information, time, and cause of death were retrospectively collected from their medical records. Results: Among 342 admitted patients, 49 died. The time of death was as follows: within 24 h (n = 9), within 3 days (n = 7), within 1 week (n = 5), within 2 weeks (n = 4), within 3 weeks (n = 3), within 30 days (n = 6), within 60 days (n = 5), and after 60 days (n = 9). The causes of death within 3 days were hypoxic encephalopathy, extensive burns (>80%), severe heat stroke, and acute coronary syndrome. The causes of death after 3 days were sepsis, pneumonia, intestinal ischemia, pancreatitis, and worsening of chronic diseases. The mortality rate was similar for patients ≥65 years of age and those with a burn area of ≥20%, with both groups showing a particularly poor prognosis. Conclusions: The timing of death in hospitalized burn patients showed a bimodal distribution as approximately 40% of patients who survived the resuscitation period died after 30 days. Elderly patients were at particularly high risk for mortality. In burn care, treatment planning should consider not only the short-term but also the long-term prognosis.

Assessing associated factors for failure of nonoperative management in pediatric blunt liver and spleen injuries: a secondary analysis of the SHIPPs study.

PURPOSE: The purpose of this study was to describe the characteristics of pediatric patients who underwent nonoperative management (NOM) for blunt splenic and hepatic injuries and to explore factors associated with NOM failure. METHODS: This was a secondary analysis of a multicenter cohort study of pediatric patients with blunt liver and spleen injuries in Japan. Participants included pediatric trauma patients aged 16 years or younger between 2008 and 2019 with NOM, which was defined as no surgery provided within 6 h of hospital arrival. NOM failure, defined as abdominal surgery performed after 6 h of hospital arrival, was the primary outcome. Descriptive statistics were provided and exploratory analysis to assess the associations with outcome using logistic regression. RESULTS: During the study period, 1339 met our eligibility criteria. The median age was 9 years, with a majority being male. The median Injury Severity Score (ISS) was 10. About 14.0% required transfusion within 24 h, and 22.3% underwent interventional radiology procedures. NOM failure occurred in 1.0% of patients and the in-hospital mortality was 0.7%. Factors associated with NOM failure included age, positive focused assessment with sonography for trauma (FAST), contrast extravasation on computed tomography (CT), severe liver injury, concomitant pancreas injury, concomitant gastrointestinal injury, concomitant mesenteric injury, and ISS. CONCLUSIONS: In our study, NOM failure were rare. Older age, positive FAST, contrast extravasation on CT, severe liver injury, concomitant pancreas injury, concomitant gastrointestinal injury, concomitant mesenteric injury, and higher ISS were suggested as possible risk factors for NOM failure.

Plasma Proteomics Profile-Based Comparison of Torso Versus Brain Injury: A Prospective Cohort Study.

INTRODUCTION: Trauma-related deaths and post-traumatic sequelae are a global health concern, necessitating a deeper understanding of the pathophysiology to advance trauma therapy. Proteomics offers insights into identifying and analyzing plasma proteins associated with trauma and inflammatory conditions; however, current proteomic methods have limitations in accurately measuring low-abundance plasma proteins. This study compared plasma proteomics profiles of patients from different acute trauma subgroups to identify new therapeutic targets and devise better strategies for personalized medicine. METHODS: This prospective observational single-center cohort study was conducted between August 2020 and September 2021 in the intensive care unit of Osaka University Hospital in Japan. Enrolling 59 consecutive patients with blunt trauma, we meticulously analyzed plasma proteomics profiles in participants with torso or head trauma, comparing them with those of controls (mild trauma). Using the Olink Explore 3072® instrument, we identified five endotypes (α-ε) via unsupervised hierarchical clustering. RESULTS: The median time from injury to blood collection was 47 minutes [interquartile range: 36-64 minutes]. The torso trauma subgroup exhibited 26 unique proteins with significantly altered expression, while the head trauma subgroup showed 68 unique proteins with no overlap between the two. The identified endotypes included α (torso trauma, n = 8), ß (young patients with brain injury, n = 5), γ (severe brain injury post-surgery, n = 8), δ (torso or brain trauma with mild hyperfibrinolysis, n = 18), and ε (minor trauma, n = 20). Patients with torso trauma showed changes in blood pressure, smooth muscle adaptation, hypermetabolism, and hypoxemia. Patients with traumatic brain injury had dysregulated blood coagulation and altered nerves regeneration and differentiation. CONCLUSIONS: This study identified unique plasma protein expression patterns in patients with torso trauma and traumatic brain injury, helping categorize five distinct endotypes. Our findings may offer new insights for clinicians, highlighting potential strategies for personalized medicine and improved trauma-related care. LEVEL OF EVIDENCE: Prospective Cohort Study, Level III.

Elective surgery for liver injury and misinserted tube into the inferior vena cava associated with chest tube replacement: A case report.

Background: Several reports on organ injury and death due to incorrect chest tube insertion exist; however, reports on the chest tube penetrating the liver and reaching the inferior vena cava are limited. Case Presentation: A 79-year-old man presented with a clamped tube because of massive bleeding from the tube following right chest tube replacement in the hospital of origin. The tube entered the inferior vena cava from the hepatic parenchyma via the right hepatic vein and was removed 15 h later because his hemodynamics stabilized. A ruptured pseudoaneurysm necessitated further transcatheter arterial embolism on the second hospitalization day, and the patient was transferred back to the referring hospital on day 17. Conclusion: Liver injury caused by an inferior vena cava misinsertion-associated chest tube can be treated with elective surgery in anticipation of the tube's tamponade effect. However, due to the risk of rebleeding, imaging follow-up is necessary soon after surgery.

Relationship between extravascular leakage and clinical outcome on computed tomography of isolated traumatic brain injury.

Aim: This study investigated whether contrast extravasation on computed tomography (CT) angiography in patients with traumatic brain injury (TBI) is associated with death or surgical procedures. Methods: Patients over 18 years old, directly brought in by ambulance with an isolated head injury and confirmed to have acute intracranial hemorrhage on a CT scan upon admission between 2010 and 2020, were included. The primary outcome was mortality, and the secondary outcome was neurosurgical procedures performed from admission to discharge from the intensive care unit. Multivariable logistic regression analyses were performed to evaluate the association between these outcomes and contrast extravasation. Results: The analysis included 188 patients with a median age of 65 years, 123 men (65.4%), 34 deaths (18.1%), and 91 surgeries (48.4%). Among the 66 patients with contrast extravasation, 22 (33.3%) died and 47 (71.2%) required surgery. Among the 122 patients with no contrast extravasation, 12 (9.8%) died, and 44 (36.1%) required surgery. The presence or absence of extravascular leakage was associated with death (odds ratio, 3.6 [95% CI: 1.2-12.2]) and surgery (odds ratio, 7.6 [95% CI: 2.5-22.7]). Conclusion: Contrast extravasation was associated with mortality and performance of surgery in patients with an isolated head injury.

T cell dysfunction in elderly ARDS patients based on miRNA and mRNA integration analysis.

Background: Acute respiratory distress syndrome (ARDS) is respiratory failure that commonly occurs in critically ill patients, and the molecular mechanisms underlying its pathogenesis and severity are poorly understood. We evaluated mRNA and miRNA in patients with ARDS and elucidated the pathogenesis of ARDS after performing mRNA and miRNA integration analysis. Methods: In this single-center, prospective, observational clinical study of patients with ARDS, peripheral blood of each patient was collected within 24 hours of admission. Sequencing of mRNA and miRNA was performed using whole blood from the ARDS patients and healthy donors. Results: Thirty-four ARDS patients were compared with 15 healthy donors. Compared with the healthy donors, 1233 mRNAs and 6 miRNAs were upregulated and 1580 mRNAs and 13 miRNAs were downregulated in the ARDS patients. For both mRNA and miRNA-targeted mRNA, canonical pathway analysis showed that programmed death-1 (PD-1) and programmed cell death ligand 1 (PD-L1) cancer immunotherapy pathway was most activated and the Th2 pathway was most suppressed. For mRNA, the Th1 pathway was most suppressed. miR-149-3p and several miRNAs were identified as upstream regulators. Conclusion: miRNAs regulated the PD-1 and PD-L1 cancer immunotherapy pathway and Th2 pathway through miRNA interference action of mRNA. Integrated analysis of mRNAs and miRNAs showed that T cells were dysfunctional in ARDS patients.

Factors associated with difficulty in hospital acceptance during the COVID-19 pandemic period in Osaka Prefecture, Japan: a population-based study.

Background: In many countries, emergency medical systems were responsible for initial treatment of patients with COVID-19. Generally, acceptance by medical institutions may not be sufficient, and it may take much time to determine the medical institution to which to transport the patient. This problem is termed "difficulty in hospital acceptance (DIH)," and it is used as a key performance indicator in the assessment of the EMS in Japan. The purpose of this study was to reveal the factors associated with the DIH during the COVID-19 pandemic using dataset in the ORION (Osaka emergency information Research Intelligent Operation Network system). Methods: This was a retrospective descriptive study with a 3-year study period from January 1, 2019 to December 31, 2021. We included patients who were recorded in the ORION system during the study period. The primary endpoint was defined as DIH. Multivariable logistic regression model was used to assess factors associated with DIH during the COVID-19 pandemic and calculated their adjusted odds ratio (AOR) and associated 95% confidence interval (CI). Results: 1,078,850 patients included in this study. Of them, 41,140 patients (3.8%) experienced DIH and 1,037,710 patients (96.2%) did not experience DIH. The median age was 71 years (IQR: 45-82), and 543,760 patients (50.4%) were male. In this study, SpO2, body temperature, and epidemic period of COVID-19 were associated with difficulty in hospital acceptance. The highest AOR of SpO2 was 80% or less (AOR: 1.636, [95% CI: 1.532-1.748]), followed by 81-85% (AOR: 1.584, [95% CI: 1.459-1.721]). The highest AOR of body temperature was 38.0-38.9°C (AOR: 1.969 [95% CI: 1.897-2.043]), followed by 39°C or higher (AOR: 1.912 [95% CI: 1.829-1.998]). The highest AOR of epidemic period of COVID-19 was the 4th wave (AOR: 2.134, [95% CI: 2.065-2.205]), followed by the 3rd wave (AOR: 1.842, [95% CI: 1.785-1.901]). Conclusion: In this study, we revealed factors associated with the DIH during the COVID-19 pandemic. As various factors are involved in the spread of an unknown infectious disease, it is necessary not only to plan in advance but also to take appropriate measures according to the situation in order to smoothly accept emergency patients.

Impact of pre-existing medical conditions on mortality in geriatric trauma: a nationwide study in Japan.

PURPOSE: To investigate the relationship between pre-existing medical conditions and outcomes in elderly trauma patients in Japan. METHODS: This multicenter observational study utilized data from the Japan Trauma Data Bank (JTDB) from 2019 to 2020. The primary outcome was in-hospital mortality. Factors associated with in-hospital mortality were identified using multivariate logistic regression analysis, from which adjusted odds ratios (AOR) and 95% confidence intervals (CI) were determined. RESULTS: Of the participants during the study period, 19,598 patients were included in the analysis. Among the pre-existing medical conditions, moderate or severe liver disease showed the strongest positive association with in-hospital mortality (AOR: 7.087, 95% CI: 3.194-15.722), followed by multiple malignancies (AOR: 3.490, 95% CI: 1.046-11.641), congestive heart failure (AOR: 2.572, 95% CI: 1.920-3.445), and moderate or severe renal disease (AOR: 2.256, 95% CI: 1.584-3.215). CONCLUSION: Data from JTDB suggests that pre-existing conditions like moderate or severe liver disease, congestive heart failure, and moderate or severe renal disease in elderly trauma patients are positively correlated with in-hospital mortality.

Dysbiosis of gut microbiota in patients with severe COVID-19.

Aim: Altered gut microbiota has been proposed as one of the causes of exacerbation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2/COVID-19) from the perspective of the gut-lung axis. We aimed to evaluate gut microbiota in mechanically ventilated patients with COVID-19 prior to using antibiotics. Methods: We retrospectively selected for enrollment COVID-19 patients who required mechanical ventilation on admission but who had not used antibiotics before admission to observe the influence of SARS-Cov-2 on gut microbiota. Fecal samples were collected serially on admission and were evaluated by 16S rRNA gene deep sequencing. Results: The phylum of Bacteroidetes decreased, and those of Firmicutes and Actinobacteria increased in COVID-19 patients compared with those in healthy controls (p < 0.001). The main commensals of Bacteroides, Faecalibacterium, and Blautia at the genus level were significantly decreased in the COVID-19 patients, and opportunistic bacteria including Corynebacterium, Anaerococcus, Finegoldia Peptoniphilus, Actinomyces, and Enterococcus were increased (p < 0.001). α-Diversity and ß-diversity in COVID-19 patients significantly changed compared with those in the healthy controls. Conclusion: The commensal gut microbiota were altered, and opportunistic bacteria increased in patients with severe COVID-19 who required mechanical ventilation on admission.

Effects of Concomitant Traumatic Spinal Cord and Brain Injury on In-Hospital Mortality: A Retrospective Analysis of a Nationwide Trauma Registry in Japan.

Isolated traumatic spinal cord injury (t-SCI) and traumatic brain injury (TBI) represent significant public health concerns, resulting in long-term disabilities and necessitating sophisticated care, particularly when occurring concurrently. The impact of these combined injuries, while crucial in trauma management, on clinical, socioeconomic, and health care outcomes is largely unknown. To address this gap, our secondary retrospective cohort study used data from the Japan Trauma Data Bank, covering patients enrolled over a 13-year period (2006-2018), to elucidate the effects of concurrent t-SCI and TBI on in-hospital mortality. Data on patient demographics, injury characteristics, treatment modalities, and outcomes were analyzed. Multivariate logistic regression analysis was performed to examine prognostic variables associated with in-hospital mortality, including interaction terms between t-SCI severity and TBI presence. This study included 91,983 patients with neurotrauma, with a median age of 62 years (69.7% men). Among the patients, 9,018 (9.8%) died in the hospital. Concomitant t-SCI and TBI occurred in 2,954 (3.2%) patients. t-SCI only occurred in 9,590 (10.4%) patients, whereas TBI only occurred in the majority of these cases (79,439, 86.4%). Multivariate logistic regression analysis revealed age; sex; total number of comorbidities; systolic blood pressure at presentation; Glasgow coma scale score at presentation; and Abbreviated Injury Scale (AIS) scores for head, face, chest, abdomen, cervical-SCI, thoracic-SCI, and lumbar-SCI as significant independent factors for in-hospital mortality. The odds ratio of cervical-SCI × head AIS as an interaction term was 0.85 (95% confidence interval: 0.77-0.95), indicating a negative interaction. In conclusion, we identified 12 factors associated with in-hospital mortality in patients with t-SCI. In addition, the negative interaction between cervical t-SCI and TBI suggests that the presence of t-SCI in patients with TBI may be underestimated. This study highlights the importance of early recognition and comprehensive management of these complex trauma conditions while considering the possibility of concomitant t-SCI in patients with TBI.

Can Gram staining be a guiding tool for optimizing initial antimicrobial agents in bacterial infections?

The emergence of multidrug-resistant organisms poses a significant threat to global public health, making the optimization of antimicrobial use crucial. Antimicrobial therapy is often initiated in emergency rooms (ERs) and intensive care units (ICUs), where patients are at high risk of infection. Prompt antimicrobial selection is essential in these facilities, and point-of-care testing can guide the appropriate initial antimicrobial therapy. Gram staining, a quick and inexpensive method, was previously used for point-of-care testing by physicians in the 1980s but was discontinued in 1988 in the United States. However, in Japan, the clinical practice of Gram stain-based antimicrobial therapy by physicians has continued in a limited number of hospitals. Several studies undertaken in Japan have shown that Gram staining carried out by trained physicians can reduce the overuse of broad-spectrum antimicrobial agents in ERs and ICUs without worsening patients' outcomes. Gram stain-based antimicrobial therapy reduced unnecessary use of carbapenems in the ER. Furthermore, Gram staining has been shown to significantly reduce the overuse of broad-spectrum antimicrobials without worsening clinical cure and mortality for patients with ventilator-associated pneumonia in the ICU. The classic technique of Gram staining has regained its usefulness through persistent clinical practice in Japan. It is hoped that Japanese researchers in this field will demonstrate to the world the efficacy of the classic technique of Gram staining in addressing this critical problem. Gram staining carried out by trained physicians could serve as a valuable means of optimizing antimicrobial treatment in ERs and ICUs.

Anticoagulant therapies against sepsis-induced disseminated intravascular coagulation.

Disseminated intravascular coagulation (DIC) is a frequent but lethal complication in sepsis. Anticoagulant therapies, such as heparin, antithrombin, activated protein C, and recombinant human-soluble thrombomodulin, were expected to regulate the progression of coagulopathy in sepsis. Although a number of randomized controlled trials (RCTs) have evaluated the survival effects of these therapies over the past few decades, there remains no consistent evidence showing a significant survival benefit of anticoagulant therapies. Currently, anticoagulant therapies are not conducted as a standard treatment against sepsis in many countries and regions. However, most of these RCTs were performed overall in patients with sepsis but not in those with sepsis-induced DIC, who were theoretically the optimal target population of anticoagulants. Actually, multiple lines of evidence from observational studies and meta-analyses of the RCTs have suggested that anticoagulant therapies might reduce mortality only when used in septic DIC. In addition, the severity of illness is another essential factor that maximally affects the efficacy of the therapy. Therefore, to provide evidence on the true effect of anticoagulant therapies, the next RCTs must be designed to enroll only patients with sepsis-induced overt DIC and a high severity of illness. To prepare these future RCTs, a novel scientific infrastructure for accurate detection of patients who can receive maximal benefit from anticoagulant therapies also needs to be established.