This novel trauma workflow, comprising immediate CT diagnosis and rapid bleeding control without patient transfer, as realized in the Hybrid ER, may improve mortality in severe trauma.This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0.

IntroductionWhole-body computed tomography (CT) has gained importance in the early diagnostic phase of trauma care. However, the diagnostic value of CT for seriously injured patients is not thoroughly clarified. This study assessed whether preoperative CT beneficially affected survival of patients with blunt trauma who required emergency bleeding control.MethodsThis retrospective study was conducted from January 2004 to December 2010 in two tertiary trauma centers in Japan. The primary inclusion criterion was patients with blunt trauma who required emergency bleeding control (surgery or transcatheter arterial embolization). CT before emergency bleeding control was performed at the attending physician's discretion based on individual patient condition (for example, hemodynamic stability or certain abnormalities in the primary survey). We assessed covariates associated with 28-day mortality with multivariate logistic regression analysis and evaluated standardized mortality ratio (SMR, ratio of observed to predicted mortality by Trauma and Injury Severity Score (TRISS) method) in two subgroups of patients who did or did not undergo CT.ResultsThe inclusion criterion was fulfilled by 152 patients with a median Injury Severity Score of 35.3. During the early resuscitation phase, 132 (87%) patients underwent CT and 20 (13%) did not. Severity of injury was significantly higher in the non-CT versus CT group patients. Observed mortality rate was significantly lower in the CT versus non-CT group (18% vs. 80%, P <0.001). Multivariate adjustment for the probability of survival (Ps) by TRISS method confirmed CT as an independent predictor for 28-day mortality (adjusted OR, 7.22; 95% CI, 1.76 to 29.60; P = 0.006). In the subgroup with less severe trauma (TRISS Ps ≥50%), SMR in the CT group was 0.63 (95% CI, 0.23 to 1.03; P = 0.066), indicating no significant difference between observed and predicted mortality in the CT group. In contrast, in the subgroup with more severe trauma (TRISS Ps <50%), SMR was 0.65 (95% CI, 0.41 to 0.90; P = 0.004) only in the CT group, whereas the difference between observed and predicted mortality was not significant in the non-CT group, suggesting a possible beneficial effect of CT on survival only in trauma patients at high risk of death.ConclusionCT performed before emergency bleeding control might be associated with improved survival, especially in severe trauma patients with TRISS Ps of <50%.

BackgroundAcute pyelonephritis (APN) is a common complication of ureteral obstruction caused by urolithiasis, and it can be lethal if it progresses to septic shock. We investigated the clinical characteristics of patients undergoing emergency drainage and assessed risk factors for septic shock.MethodsA retrospective study was performed of 98 patients (101 events) requiring emergency drainage at our urology department for obstructive APN associated with upper urinary tract calculi from January 2003 to January 2011. Clinical characteristics were summarized, and risk factors for septic shock were assessed by logistic regression analysis.ResultsObjective evidence of sepsis was found in 64 (63.4%) events, and 21 events (20.8%) were categorized as septic shock. Ninety-six patients recovered, but 2 patients died of septic shock. Multivariate analysis revealed that age and the presence of paralysis were independent risk factors for septic shock.ConclusionsAPN associated with upper urinary tract calculi is a severe disease that should be treated with caution, particularly when risk factors are present.

Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge1–5. Here we conducted a genome-wide association study (GWAS) involving 2,393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3,289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target.

Recently, computed tomography (CT) has gained importance in the early diagnostic phase of trauma care in the emergency room. We implemented a new trauma workflow concept with CT in our emergency room that allows emergency therapeutic intervention without relocating the patient. Times from patient arrival to CT initiation, CT end, and definitive intervention were significantly shorter with our new protocol than were those with the conventional CT protocol. Our new workflow concept, which provides faster time to definitive intervention, appears to be effective.

To elucidate the host genetic loci affecting severity of SARS-CoV-2 infection, or Coronavirus disease 2019 (COVID-19), is an emerging issue in the face of the current devastating pandemic. Here, we report a genome-wide association study (GWAS) of COVID-19 in a Japanese population led by the Japan COVID-19 Task Force, as one of the initial discovery GWAS studies performed on a non-European population. Enrolling a total of 2,393 cases and 3,289 controls, we not only replicated previously reported COVID-19 risk variants (e.g., LZTFL1, FOXP4, ABO, and IFNAR2), but also found a variant on 5p35 (rs60200309-A at DOCK2) that was significantly associated with severe COVID-19 in younger (<65 years of age) patients with a genome-wide significant p-value of 1.2 × 10-8 (odds ratio = 2.01, 95% confidence interval = 1.58-2.55). This risk allele was prevalent in East Asians, including Japanese (minor allele frequency [MAF] = 0.097), but rarely found in Europeans. Cross-population Mendelian randomization analysis made a causal inference of a number of complex human traits on COVID-19. In particular, obesity had a significant impact on severe COVID-19. The presence of the population-specific risk allele underscores the need of non-European studies of COVID-19 host genetics.

Background We aimed to elucidate differences in the characteristics of patients with coronavirus disease 2019 (COVID-19) requiring hospitalization in Japan, by COVID-19 waves, from conventional strains to the Delta variant. Methods We used secondary data from a database and performed a retrospective cohort study that included 3261 patients aged ≥ 18 years enrolled from 78 hospitals that participated in the Japan COVID-19 Task Force between February 2020 and September 2021. Results Patients hospitalized during the second (mean age, 53.2 years [standard deviation {SD}, ± 18.9]) and fifth (mean age, 50.7 years [SD ± 13.9]) COVID-19 waves had a lower mean age than those hospitalized during the other COVID-19 waves. Patients hospitalized during the first COVID-19 wave had a longer hospital stay (mean, 30.3 days [SD ± 21.5], p < 0.0001), and post-hospitalization complications, such as bacterial infections (21.3%, p < 0.0001), were also noticeable. In addition, there was an increase in the use of drugs such as remdesivir/baricitinib/tocilizumab/steroids during the latter COVID-19 waves. In the fifth COVID-19 wave, patients exhibited a greater number of presenting symptoms, and a higher percentage of patients required oxygen therapy at the time of admission. However, the percentage of patients requiring invasive mechanical ventilation was the highest in the first COVID-19 wave and the mortality rate was the highest in the third COVID-19 wave. Conclusions We identified differences in clinical characteristics of hospitalized patients with COVID-19 in each COVID-19 wave up to the fifth COVID-19 wave in Japan. The fifth COVID-19 wave was associated with greater disease severity on admission, the third COVID-19 wave had the highest mortality rate, and the first COVID-19 wave had the highest percentage of patients requiring mechanical ventilation.

Computed tomography (CT) embedded in the emergency room has gained importance in the early diagnostic phase of trauma care. In 2011, we implemented a new trauma workflow concept with a sliding CT scanner system with interventional radiology features (IVR-CT) that allows CT examination and emergency therapeutic intervention without relocating the patient, which we call the Hybrid emergency room (Hybrid ER). In the Hybrid ER, all life-saving procedures, CT examination, damage control surgery, and transcatheter arterial embolisation can be performed on the same table. Although the trauma workflow realized in the Hybrid ER may improve mortality in severe trauma, the Hybrid ER can potentially affect the efficacy of other in/outpatient diagnostic workflow because one room is occupied by one severely injured patient undergoing both emergency trauma care and CT scanning for long periods. In July 2017, we implemented a new trauma workflow concept with a dual-room sliding CT scanner system with interventional radiology features (dual-room IVR-CT) to increase patient throughput. When we perform emergency surgery or interventional radiology for a severely injured or ill patient in the Hybrid ER, the sliding CT scanner moves to the adjacent CT suite, and we can perform CT scanning of another in/outpatient. We believe that dual-room IVR-CT can contribute to the improvement of both the survival of severely injured or ill patients and patient throughput.