Diffuse bone marrow uptake on 18F-fluorodeoxyglucose positron emission tomography/computed tomography with copper-deficiency anemia.

A 59-year-old man with pancytopenia underwent 18F-fluorodeoxyglucose positron emission tomography/computed tomography for suspected carcinomatosis. The scan revealed diffuse bone marrow uptake, prompting further investigation. Bone marrow analysis revealed no malignant cells; however, erythroblasts with cytoplasmic vacuolization were observed. Subsequent testing showed low serum copper and ceruloplasmin levels, indicating copper deficiency. Copper supplementation resulted in significant improvement in cytopenia. Notably, the bone marrow uptake on subsequent scans decreased significantly. This case highlights the importance of considering copper deficiency as a potential cause of diffuse bone marrow uptake of 18F-fluorodeoxyglucose on positron emission tomography/computed tomography.

Accumulation of Immunity in Heavy-Tailed Sexual Contact Networks Shapes Mpox Outbreak Sizes.

Many countries affected by the global outbreak of mpox in 2022 have observed a decline in cases. Our mathematical model accounting for heavy-tailed sexual partnership distributions suggests that mpox epidemics can hit the infection-derived herd immunity threshold and begin to decline, with <1% of sexually active men who have sex with men infected regardless of interventions or behavioral changes. We consistently found that many countries and US states experienced an epidemic peak, with cumulative cases of around 0.1% to 0.5% among men who have sex with men. The observed decline in cases may not necessarily be attributable to interventions or behavioral changes primarily.

Effect of Inhaled Ciclesonide in Non-Critically Ill Hospitalized Patients With Coronavirus Disease 2019: A Multicenter Observational Study in Japan.

Background: Coronavirus disease 2019 (COVID-19) is an ongoing global pandemic. Although systemic steroids play an important role in treating patients with severe COVID-19, the role of inhaled corticosteroids in non-critically ill, hospitalized patients with COVID-19 remains unclear. Methods: We analyzed findings in non-critically ill, hospitalized patients with COVID-19 who were >18 years old and were admitted to 64 Japanese hospitals between January and September 2020. We performed propensity score matching analysis to evaluate 28-day and in-hospital mortality rates with or without inhaled ciclesonide within 2 days of admission. Sensitivity analyses using inverse probability weighting analysis, and generalized estimating equation method were also performed. Results: Eligible patients (n = 3638) were divided into ciclesonide (n = 290) and control (n = 3, 393) groups. The 1-to-4 propensity score matching analysis included 271 ciclesonide users and 1084 nonusers. There were no significant differences between the 2 groups for 28-day (3.3% vs 2.3%; risk difference, 1.0% [95% confidence interval, -1.2 to 3.3]) or in-hospital (4.8% vs 2.6%; risk difference, 2.2 [-.5 to 4.9]) mortality rates. The sensitivity analysis showed similar outcomes. Conclusions: From this multicenter observational study in Japan, inhaled ciclesonide did not decrease 28-day or in-hospital mortality rates in non-critically ill, hospitalized patients with COVID-19. Future large, multinational, randomized trials are required to confirm our results.

Optogenetic stimulation of vagal nerves for enhanced glucose-stimulated insulin secretion and ß cell proliferation.

The enhancement of insulin secretion and of the proliferation of pancreatic ß cells are promising therapeutic options for diabetes. Signals from the vagal nerve regulate both processes, yet the effectiveness of stimulating the nerve is unclear, owing to a lack of techniques for doing it so selectively and prolongedly. Here we report two optogenetic methods for vagal-nerve stimulation that led to enhanced glucose-stimulated insulin secretion and to ß cell proliferation in mice expressing choline acetyltransferase-channelrhodopsin 2. One method involves subdiaphragmatic implantation of an optical fibre for the photostimulation of cholinergic neurons expressing a blue-light-sensitive opsin. The other method, which suppressed streptozotocin-induced hyperglycaemia in the mice, involves the selective activation of vagal fibres by placing blue-light-emitting lanthanide microparticles in the pancreatic ducts of opsin-expressing mice, followed by near-infrared illumination. The two methods show that signals from the vagal nerve, especially from nerve fibres innervating the pancreas, are sufficient to regulate insulin secretion and ß cell proliferation.

Associated organs and system with COVID-19 death with information of organ support: a multicenter observational study.

BACKGROUND: The organ dysfunction that is associated with death in COVID-19 patients has not been determined in multicenter epidemiologic studies. In this study, we evaluated the major association with death, concomitant organ dysfunction, and proportion of multiple organ failure in deaths in patients with COVID-19, along with information on organ support. METHODS: We performed an observational cohort study using the Japanese multicenter research of COVID-19 by assembling a real-world data (J-RECOVER) study database. This database consists of data on patients discharged between January 1 and September 31, 2020, with positive SARS-CoV-2 test results, regardless of intensive care unit admission status. These data were collected from the Diagnosis Procedure Combination and electronic medical records of 66 hospitals in Japan. The clinician identified and recorded the organ responsible for the death of COVID-19. RESULTS: During the research period, 4,700 patients with COVID-19 were discharged from 66 hospitals participating in the J-RECOVER study; of which, 272 patients (5.8%) from 47 institutions who died were included in this study. Respiratory system dysfunction (87.1%) was the leading association with death, followed by cardiovascular (4.8%), central nervous (2.9%), gastrointestinal (2.6%), and renal (1.1%) dysfunction. Most patients (96.7%) who died of COVID-19 had respiratory system damage, and about half (48.9%) had multi-organ damage. Of the patients whose main association with death was respiratory dysfunction, 120 (50.6%) received mechanical ventilation. CONCLUSION: This study showed that although respiratory dysfunction was the most common association with death in many cases, multi-organ dysfunction was associated with death due to COVID-19.

Estimation of waning vaccine effectiveness from population-level surveillance data in multi-variant epidemics.

Monitoring time-varying vaccine effectiveness (e.g., due to waning of immunity and the emergence of novel variants) provides crucial information for outbreak control. Existing studies of time-varying vaccine effectiveness have used individual-level data, most importantly dates of vaccination and variant classification, which are often not available in a timely manner or from a wide range of population groups. We present a novel Bayesian framework for estimating the waning of variant-specific vaccine effectiveness in the presence of multi-variant circulation from population-level surveillance data. Applications to simulated outbreaks and the COVID-19 epidemic in Japan are also presented. Our results show that variant-specific waning vaccine effectiveness estimated from population-level surveillance data could approximately reproduce the estimates from previous test-negative design studies, allowing for rapid, if crude, assessment of the epidemic situation before fine-scale studies are made available.

Trends in massive transfusion practice for trauma in Japan from 2011 to 2020: a nationwide inpatient database study.

BACKGROUND: Previous studies have reported conflicting results regarding fresh frozen plasma (FFP)-to-red blood cell (RBC) ratio and platelet-to-RBC ratio on outcomes for massive transfusion for trauma. Moreover, nationwide data on massive transfusion practices for trauma in the real-world clinical setting are scarce. This study aimed to examine the nationwide practice patterns and trends in massive transfusion for trauma in Japan using a national administrative, inpatient database. METHOD: We identified patients who underwent emergency hospitalization for trauma and received massive transfusion, defined as administration of at least 20 units of RBC within the first 2 days of admission, using the nationwide inpatient database, which covers approximately 90% of all tertiary emergency hospitals in Japan, between 2011 and 2020. Trends in the incidence and practice patterns of massive transfusion were described by calendar year. The association of practice patterns with mortality or adverse events was tested. RESULTS: A total of 3,530,846 trauma hospitalizations were identified, of which 5247 (0.15%) received massive transfusion. A significant declining trend was observed in the incidence of massive transfusion in trauma hospitalizations from 0.24% in 2011 to 0.10% in 2020 (P for trend < 0.001). The FFP-to-RBC ratio rose significantly from 0.77 in 2011 to 1.08 in 2020 (P for trend < 0.001), while the platelet-to-RBC ratio remained virtually unchanged from 0.71 in 2011 to 0.78 in 2020 (P for trend 0.060). Massive transfusion with lower FFP-to-RBC (< 0.75) and platelets-to-RBC ratio (< 1.00) were associated with increased in-hospital mortality compared with those ≥ 1.00, while there were linear increases in adverse events with increasing FFP and platelets ratios. CONCLUSIONS: This study demonstrated a declining trend in the incidence and a rise in higher FFP-to-RBC ratios in massive transfusion in association with patient outcomes for trauma from 2011 to 2020 in Japan.

Early restricted oxygen therapy after resuscitation from cardiac arrest (ER-OXYTRAC): protocol for a stepped-wedge cluster randomised controlled trial.

INTRODUCTION: Cardiac arrest is a critical condition, and patients often experience postcardiac arrest syndrome (PCAS) even after the return of spontaneous circulation (ROSC). Administering a restricted amount of oxygen in the early phase after ROSC has been suggested as a potential therapy for PCAS; however, the optimal target for arterial partial pressure of oxygen or peripheral oxygen saturation (SpO2) to safely and effectively reduce oxygen remains unclear. Therefore, we aimed to validate the efficacy of restricted oxygen treatment with 94%-95% of the target SpO2 during the initial 12 hours after ROSC for patients with PCAS. METHODS AND ANALYSIS: ER-OXYTRAC (early restricted oxygen therapy after resuscitation from cardiac arrest) is a nationwide, multicentre, pragmatic, single-blind, stepped-wedge cluster randomised controlled trial targeting cases of non-traumatic cardiac arrest. This study includes adult patients with out-of-hospital or in-hospital cardiac arrest who achieved ROSC in 39 tertiary centres across Japan, with a target sample size of 1000. Patients whose circulation has returned before hospital arrival and those with cardiac arrest due to intracranial disease or intoxication are excluded. Study participants are assigned to either the restricted oxygen (titration of a fraction of inspired oxygen with 94%-95% of the target SpO2) or the control (98%-100% of the target SpO2) group based on cluster randomisation per institution. The trial intervention continues until 12 hours after ROSC. Other treatments for PCAS, including oxygen administration later than 12 hours, can be determined by the treating physicians. The primary outcome is favourable neurological function, defined as cerebral performance category 1-2 at 90 days after ROSC, to be compared using an intention-to-treat analysis. ETHICS AND DISSEMINATION: This study has been approved by the Institutional Review Board at Keio University School of Medicine (approval number: 20211106). Written informed consent will be obtained from all participants or their legal representatives. Results will be disseminated via publications and presentations. TRIAL REGISTRATION NUMBER: UMIN Clinical Trials Registry (UMIN000046914).

Phagocytosis by macrophages promotes pancreatic ß cell mass reduction after parturition in mice.

Elucidating the mechanism(s) modulating appropriate tissue size is a critical biological issue. Pancreatic ß cells increase during pregnancy via cellular proliferation, but how ß cells promptly decrease to the original amount after parturition remains unclear. Herein, we demonstrate the role and mechanism of macrophage accumulation in this process. In the final stage of pregnancy, HTR1D signaling upregulates murine ß cell CXCL10, thereby promoting macrophage accumulation in pancreatic islets via the CXCL10-CXCR3 axis. Blocking this mechanism by administering an HTR1D antagonist or the CXCR3 antibody and depleting islet macrophages inhibited postpartum ß cell mass reduction. ß cells engulfed by macrophages increased in postpartum islets, but Annexin V administration suppressed this engulfment and the postpartum ß cell mass reduction, indicating the accumulated macrophages to phagocytose ß cells. This mechanism contributes to both maintenance of appropriate ß cell mass and glucose homeostasis promptly adapting to reduced systemic insulin demand after parturition.

A case of fulminant myocarditis with full recovery after a 38-h sustained asystole.

Key Clinical Message: Even if cardiac rhythm deteriorated to asystole in the clinical course of fulminant myocarditis, cardiac function may recover, and the patient may be discharged without brain damage, if circulation could be maintained by appropriate mechanical cardiac supports. Abstract: A 69-year-old man was diagnosed with fulminant myocarditis with circulatory collapse. His cardiac rhythm deteriorated to asystole on the second day; however, circulatory status was maintained through extracorporeal membrane oxygenation and intra-aortic balloon pumping. After 38 h-lasting asystole, his heart resumed beating. He was discharged without neurological deficits on Day 25.

Manual Chest Compression versus Automated Chest Compression Device during Day-Time and Night-Time Resuscitation Following Out-of-Hospital Cardiac Arrest: A Retrospective Historical Control Study.

OBJECTIVE: We assessed the effectiveness of automated chest compression devices depending on the time of admission based on the frequency of iatrogenic chest injuries, the duration of in-hospital resuscitation efforts, and clinical outcomes among out-of-hospital cardiac arrest (OHCA) patients. METHODS: We conducted a retrospective historical control study of OHCA patients in Japan between 2015-2022. The patients were divided according to time of admission, where day-time was considered 07:00-22:59 and night-time 23:00-06:59. These patients were then divided into two categories based on the in-hospital cardiopulmonary resuscitation (IHCPR) device: manual chest compression (mCC) group and automatic chest compression devices (ACCD) group. We used univariate and multivariate ordered logistic regression models adjusted for pre-hospital confounders to evaluate the impact of ACCD use during IHCPR on outcomes (IHCPR duration, CPR-related chest injuries, and clinical outcomes) in the day-time and night-time groups. RESULTS: Among 1101 patients with OHCA (day-time, 809; night-time, 292), including 215 patients who underwent ACCD during IHCPR in day-time (26.6%) and 104 patients in night-time group (35.6%), the multivariate model showed a significant association of ACCD use with the outcomes of in-hospital resuscitation and higher rates of return in spontaneous circulation, lower incidence of CPR-related chest injuries, longer in-hospital resuscitation durations, greater survival to Emergency Department and hospital discharge, and greater survival with good neurological outcome to hospital discharge, though only in the night-time group. CONCLUSIONS: Patients who underwent ACCD during in-hospital resuscitation at night had a significantly longer duration of in-hospital resuscitation, a lower incidence of CPR-related chest injuries, and better outcomes.

Effectiveness of intravenous immunoglobulin therapy for invasive group A Streptococcus infection: A Japanese nationwide observational study.

OBJECTIVES: Invasive group A Streptococcus infection (iGAS) is a rare but fatal condition. We aimed to evaluate the effectiveness of intravenous immunoglobulin (IVIG) in the treatment of iGAS. METHODS: Patients' data were extracted from a Japanese nationwide database between April 2018 and March 2021. The primary outcome was in-hospital mortality rate, whereas the secondary outcomes were 30-day and 7-day mortality rates. RESULTS: Overall, 481 patients (median age, 65 years; female, 49.7%) were included in the analysis. The overall mortality rate was 31.0%. After adjusting for background factors, we found that IVIG treatment had no effect on in-hospital mortality (adjusted odds ratio [OR]: 0.99, 95% confidence interval [CI]: 0.93-1.04, P = 0.92). Similar results were obtained after propensity score matching (OR: 1.00, 95% CI: 0.62-1.61, P >0.99). The 7-day and 30-day mortality rates were not associated with IVIG treatment. CONCLUSION: IVIG administration had no survival benefit in iGAS patients. However, these overall findings should not be extrapolated to streptococcal toxic shock syndrome as the effect of IVIG therapy in this condition remains uncertain. Considering the rarity of iGAS, conducting a randomized controlled trial may be impractical. Therefore, an equivalent or more extensive observational study is warranted to validate these findings.

Time-saving effect of real-time ultrasound-guided cannulation for extracorporeal cardiopulmonary resuscitation: A multicenter retrospective cohort study.

BACKGROUND: Extracorporeal cardiopulmonary resuscitation (ECPR), a bridge to treatments for cardiac arrest patients, can be technically challenging and requires expertise. While ultrasound guidance is frequently used for vascular access, its effects on cannulation time in patients treated with ECPR are poorly defined. We hypothesized that real-time ultrasound guidance would contribute to faster and safer cannulation for ECPR. METHODS: This nationwide, multicenter, retrospective study analyzed data from 36 Japanese institutions. Patients who were over age 18 years and underwent ECPR between January 1, 2013, and December 31, 2018, were included. Patients who underwent open surgical vascular access were excluded. Cannulation time and outcomes of patients who underwent real-time ultrasound-guided cannulation (i.e., ultrasound-guided group) were compared to those cannulated without the use of real-time ultrasound guidance (control group) using propensity score matching analysis. RESULTS: The ultrasound-guided group comprised 510 cases, whereas the control group comprised 941 cases. Of those, 443 propensity score-matched pairs were evaluated. Cannulation time in the ultrasound-guided group was 2.5 minutes shorter than in the control group [difference, -2.5 minutes; 95% Confidence interval (CI), -3.7 to -1.3, p < 0.001]. The incidence of catheter-related complications and the incidence of the poor neurological outcomes (Cerebral Performance Category ≥3) did not differ between groups [Odds ratio (OR), 1.51; 95% CI, 0.64-3.74; OR, 1.08; 95% CI, 0.83-1.59]. CONCLUSION: Real-time ultrasound-guided cannulation was associated with shorter cannulation time of ECPR.

Association between obesity and mortality in critically ill COVID-19 patients requiring invasive mechanical ventilation: a multicenter retrospective observational study.

This study aimed to determine whether obesity and disease outcomes are associated in patients with critically-ill coronavirus disease 2019 (COVID-19) requiring invasive mechanical ventilation (IMV). This retrospective observational study using Japanese multicenter registry data included COVID-19 patients who required IMV and were discharged between January and September 2020. The patients were divided into the obese (body mass index [BMI] ≥ 25 kg/m2) and nonobese (BMI < 25 kg/m2) groups. Logistic regression models were used to analyze the association between obesity and disease outcomes. The primary outcome was in-hospital mortality; the secondary outcome was venovenous extracorporeal membrane oxygenation (VV-ECMO) implementation. Altogether, 477 patients were enrolled (obese, n = 235, median BMI, 28.2 kg/m2; nonobese, n = 242, median BMI, 22.4 kg/m2). Obesity was significantly associated with lower in-hospital mortality in the unadjusted logistic regression model (odds ratio 0.63; 95% confidence interval, 0.42-0.97; p = 0.033), but not with mortality in the adjusted logistic regression model using age, sex, and Charlson Comorbidity Index as covariates (p = 0.564). Obesity was not associated with VV-ECMO implementation in both unadjusted and adjusted models (unadjusted, p = 0.074; adjusted, p = 0.695). Obesity was not associated with outcomes in COVID-19 patients requiring IMV. Obesity may not be a risk factor for poor outcomes in these patients.

The Restrictive Red Blood Cell Transfusion Strategy for Critically Injured Patients (RESTRIC) trial: a cluster-randomized, crossover, non-inferiority multicenter trial of restrictive transfusion in trauma.

BACKGROUND: The efficacies of fresh frozen plasma and coagulation factor transfusion have been widely evaluated in trauma-induced coagulopathy management during the acute post-injury phase. However, the efficacy of red blood cell transfusion has not been adequately investigated in patients with severe trauma, and the optimal hemoglobin target level during the acute post-injury and resuscitation phases remains unclear. Therefore, this study aimed to examine whether a restrictive transfusion strategy was clinically non-inferior to a liberal transfusion strategy during the acute post-injury phase. METHODS: This cluster-randomized, crossover, non-inferiority multicenter trial was conducted at 22 tertiary emergency medical institutions in Japan and included adult patients with severe trauma at risk of major bleeding. The institutions were allocated a restrictive or liberal transfusion strategy (target hemoglobin levels: 7-9 or 10-12 g/dL, respectively). The strategies were applied to patients immediately after arrival at the emergency department. The primary outcome was 28-day survival after arrival at the emergency department. Secondary outcomes included transfusion volume, complication rates, and event-free days. The non-inferiority margin was set at 3%. RESULTS: The 28-day survival rates of patients in the restrictive (n = 216) and liberal (n = 195) strategy groups were 92.1% and 91.3%, respectively. The adjusted odds ratio for 28-day survival in the restrictive versus liberal strategy group was 1.02 (95% confidence interval: 0.49-2.13). Significant non-inferiority was not observed. Transfusion volumes and hemoglobin levels were lower in the restrictive strategy group than in the liberal strategy group. No between-group differences were noted in complication rates or event-free days. CONCLUSIONS: Although non-inferiority of the restrictive versus liberal transfusion strategy for 28-day survival was not statistically significant, the mortality and complication rates were similar between the groups. The restrictive transfusion strategy results in a lower transfusion volume. TRIAL REGISTRATION NUMBER: umin.ac.jp/ctr: UMIN000034405, registration date: 8 October 2018.

Fetal atomic bomb survivor dosimetry using the J45 series of pregnant female phantoms with realistic survivor exposure scenarios: comparisons to dose estimates in the DS02 system.

A significant source of information on radiation-induced biological effects following in-utero irradiation stems from studies of atomic bomb survivors who were pregnant at the time of exposure in Hiroshima, and to a lesser extent, from survivors in Nagasaki. Dose estimates to the developing fetus for these survivors have been assigned in prior dosimetry systems of the Radiation Effects Research Foundation as the dose to the uterine wall within the non-pregnant adult stylized phantom, originally designed for the dosimetry system DS86 and then carried forward in DS02. In a prior study, a new J45 (Japanese 1945) series of high-resolution phantoms of the adult pregnant female at 8 weeks, 15 weeks, 25 weeks, and 38-weeks post-conception was presented. Fetal and maternal organ doses were estimated by computationally exposing the pregnant female phantom series to DS02 free-in-air cumulative photon and neutron fluences at three distances from the hypocenter at both Hiroshima and Nagasaki under idealized frontal (AP) and isotropic (ISO) particle incidence. In this present study, this work was extended using realistic angular fluences (480 directions) from the DS02 system for seven radiation source terms, nine different radiation dose components, and five shielding conditions. In addition, to explore the effects of fetal position within the womb, four new phantoms were created and the same irradiation scenarios were performed. General findings are that the current DS02 fetal dose surrogate overestimates values of fetal organ dose seen in the J45 phantoms towards the cranial end of the fetus, especially in the later stages of pregnancy. For example, for in-open exposures at 1000 m in Hiroshima, the ratio of J45 fetal brain dose to DS02 uterine wall dose is 0.90, 0.82, and 0.70 at 15 weeks, 25 weeks, and 38-weeks, respectively, for total gamma exposures, and are 0.64, 0.44, and 0.37 at these same gestational ages for total neutron exposures. For organs in the abdominal and pelvic regions of the fetus, dose gradients across gestational age flatten and later reverse, so that DS02 fetal dosimetry begins to underestimate values of fetal organ dose as seen in the J45 phantoms. For example, for the same exposure scenario, the ratios of J45 fetal kidney dose to DS02 uterine wall dose are about 1.09 from 15 to 38 weeks for total gamma dose, and are 1.30, 1.56, and 1.75 at 15 weeks, 25 weeks, and 38 weeks, respectively, for the total neutron dose. Results using the new fetal positioning phantoms show this trend reversing for a head-up, breach fetal position. This work supports previous findings that the J45 pregnant female phantom series offers significant opportunities for gestational age-dependent assessment of fetal organ dose without the need to invoke the uterine wall as a fetal organ surrogate.

A highly sensitive strategy for monitoring real-time proliferation of targeted cell types in vivo.

Cell proliferation processes play pivotal roles in timely adaptation to many biological situations. Herein, we establish a highly sensitive and simple strategy by which time-series showing the proliferation of a targeted cell type can be quantitatively monitored in vivo in the same individuals. We generate mice expressing a secreted type of luciferase only in cells producing Cre under the control of the Ki67 promoter. Crossing these with tissue-specific Cre-expressing mice allows us to monitor the proliferation time course of pancreatic ß-cells, which are few in number and weakly proliferative, by measuring plasma luciferase activity. Physiological time courses, during obesity development, pregnancy and juvenile growth, as well as diurnal variation, of ß-cell proliferation, are clearly detected. Moreover, this strategy can be utilized for highly sensitive ex vivo screening for proliferative factors for targeted cells. Thus, these technologies may contribute to advancements in broad areas of biological and medical research.

Relationship between institutional ventilated COVID-19 case volume and in-hospital death: A multicenter cohort study.

BACKGROUND: The volume-outcome relationship in patients with severe Coronavirus disease 2019 (COVID-19) is unclear and is important for establishing a system for the medical care of severe COVID-19. This study aimed to evaluate the association between institutional case volume and outcomes in patients with ventilated COVID-19. METHODS: We analyzed patients with severe COVID-19 on ventilatory control aged > 17 years who were enrolled in the J-RECOVER study, which is a retrospective multicenter observational study conducted between January 2020 and September 2020 in Japan. Based on the ventilated COVID-19 case volume, the higher one-third of institutions were defined as high-volume centers, the middle one-third as middle-volume centers, and the lower one-third as low-volume centers. The primary outcome measure was in-hospital mortality during hospitalization due to COVID-19. Multivariate logistic regression analysis for in-hospital mortality and ventilated COVID-19 case volume was performed after adjusting for multiple propensity scores and in-hospital variables. To estimate the multiple propensity score, we fitted a multinomial logistic regression model, which fell into one of the three groups based on patient demographics and prehospital factors. RESULTS: We analyzed 561 patients who required ventilator management. In total, 159, 210, and 192 patients were admitted to low-volume (36 institutions, < 11 severe COVID-19 cases per institution during the study period), middle-volume (14 institutions, 11-25 severe cases per institution), and high-volume (5 institutions, > 25 severe cases per institution) centers, respectively. After adjustment for multiple propensity scores and in-hospital variables, admission to middle- and high-volume centers was not significantly associated with in-hospital death compared with admission to low-volume centers (adjusted odds ratio, 0.77 [95% confidence interval (CI): 0.46-1.29] and adjusted odds ratio, 0.76 [95% CI: 0.44-1.33], respectively). CONCLUSIONS: There may be no significant relationship between institutional case volume and in-hospital mortality in patients with ventilated COVID-19.