Suppression of Type I Interferon Signaling in Myeloid Cells by Autoantibodies in Severe COVID-19 Patients.

PURPOSE: Auto-antibodies (auto-abs) to type I interferons (IFNs) have been identified in patients with life-threatening coronavirus disease 2019 (COVID-19), suggesting that the presence of auto-abs may be a risk factor for disease severity. We therefore investigated the mechanism underlying COVID-19 exacerbation induced by auto-abs to type I IFNs. METHODS: We evaluated plasma from 123 patients with COVID-19 to measure auto-abs to type I IFNs. We performed single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells from the patients with auto-abs and conducted epitope mapping of the auto-abs. RESULTS: Three of 19 severe and 4 of 42 critical COVID-19 patients had neutralizing auto-abs to type I IFNs. Patients with auto-abs to type I IFNs showed no characteristic clinical features. scRNA-seq from 38 patients with COVID-19 revealed that IFN signaling in conventional dendritic cells and canonical monocytes was attenuated, and SARS-CoV-2-specific BCR repertoires were decreased in patients with auto-abs. Furthermore, auto-abs to IFN-α2 from COVID-19 patients with auto-abs recognized characteristic epitopes of IFN-α2, which binds to the receptor. CONCLUSION: Auto-abs to type I IFN found in COVID-19 patients inhibited IFN signaling in dendritic cells and monocytes by blocking the binding of type I IFN to its receptor. The failure to properly induce production of an antibody to SARS-CoV-2 may be a causative factor of COVID-19 severity.

Incidence and mortality of community-acquired and nosocomial infections in Japan: a nationwide medical claims database study.

BACKGROUND: It is important to determine the prevalence and prognosis of community-acquired infection (CAI) and nosocomial infection (NI) to develop treatment strategies and appropriate medical policies in aging society. METHODS: Patients hospitalized between January 2010 and December 2019, for whom culture tests were performed and antibiotics were administered, were selected using a national claims-based database. The annual trends in incidence and in-hospital mortality were calculated and evaluated by dividing the patients into four age groups. RESULTS: Of the 73,962,409 inpatients registered in the database, 9.7% and 4.7% had CAI and NI, respectively. These incidences tended to increase across the years in both the groups. Among the patients hospitalized with infectious diseases, there was a significant increase in patients aged ≥ 85 years (CAI: + 1.04%/year and NI: + 0.94%/year, P < 0.001), while there was a significant decrease in hospitalization of patients aged ≤ 64 years (CAI: -1.63%/year and NI: -0.94%/year, P < 0.001). In-hospital mortality was significantly higher in the NI than in the CAI group (CAI: 8.3%; NI: 14.5%, adjusted mean difference 4.7%). The NI group had higher organ support, medical cost per patient, and longer duration of hospital stay. A decreasing trend in mortality was observed in both the groups (CAI: -0.53%/year and NI: -0.72%/year, P < 0.001). CONCLUSION: The present analysis of a large Japanese claims database showed that NI is a significant burden on hospitalized patients in aging societies, emphasizing the need to address particularly on NI.

Efficiency and Workload Reduction of Semi-automated Citation Screening Software for Creating Clinical Practice Guidelines: A Prospective Observational Study.

BACKGROUND: We evaluated the applicability of automated citation screening in developing clinical practice guidelines. METHODS: We prospectively compared the efficiency of citation screening between the conventional (Rayyan) and semi-automated (ASReview software) methods. We searched the literature for five clinical questions (CQs) in the development of the Japanese Clinical Practice Guidelines for the Management of Sepsis and Septic Shock. Objective measurements of the time required to complete citation screening were recorded. Following the first screening round, in the primary analysis, the sensitivity, specificity, positive predictive value, and overall screening time were calculated for both procedures using the semi-automated tool as index and the results of the conventional method as standard reference. In the secondary analysis, the same parameters were compared between the two procedures using the final list of included studies after the second screening session as standard reference. RESULTS: Among the five CQs after the first screening session, the highest and lowest sensitivity, specificity, and positive predictive values were 0.241 and 0.795; 0.991 and 1.000; and 0.482 and 0.929, respectively. In the secondary analysis, the highest sensitivity and specificity in the semi-automated citation screening were 1.000 and 0.997, respectively. The overall screening time per 100 studies was significantly shorter with semi-automated than with conventional citation screening. CONCLUSION: The potential advantages of the semi-automated method (shorter screening time and higher discriminatory rate for the final list of studies) warrant further validation.

Prediction of the neurological outcomes post-cardiac arrest: A prospective validation of the CAST and rCAST.

INTRODUCTION: The neurologic prognosis of out-of-hospital cardiac arrest (OHCA) patients in whom return of spontaneous circulation (ROSC) is achieved remains poor. The aim of this study was to externally and prospectively validate two scoring systems developed by us: the CAST score, a scoring system to predict the neurological prognosis of OHCA patients undergoing targeted temperature management (TTM), and a simplified version of the same score developed for improved ease of use in clinical settings, the revised CAST (rCAST) score. METHODS: This study was a prospective, multicenter, observational study conducted using the SOS KANTO 2017 registry, an OHCA registry involving hospitals in the Kanto region (including Tokyo) of Japan. The primary outcome was favorable neurological outcome (defined as Cerebral Performance Category score of 1 or 2) at 30 days and the secondary outcomes were favorable neurological outcome at 90 days and survival at 30 and 90 days. The predictive accuracies of the original CAST (oCAST) and rCAST scores were evaluated by using area under the receiver operating characteristic curve (AUC). RESULTS: Of 9909 OHCA patients, 565 showed ROSC and received TTM. Of these, we analyzed the data of 259 patients in this study. The areas under the receiver operating characteristic curve (AUCs) of the oCAST and rCAST scores for predicting a favorable neurological outcome at 30 days were 0.86 and 0.87, respectively, and those for predicting a favorable neurological outcome at 90 days were 0.87 and 0.88, respectively. The rCAST showed a higher predictive accuracy for the neurological outcome as compared with the NULL-PLEASE score. The patients with a favorable neurological outcome who had been classified into the high severity group based on the rCAST tended to have hypothermia at hospital arrival and to not show any signs of loss of gray-white matter differentiation on brain CT. Neurological function at 90 days was correlated with the rCAST (r = 0.63, p < 0.001). CONCLUSIONS: rCAST showed high predictive accuracy for the neurological prognosis of OHCA patients managed by TTM, comparable to that of the oCAST score. The scores on the rCAST were strongly correlated with the neurological functions at 90 days, implying that the rCAST is a useful scale for assessing the severity of brain injury after cardiac arrest.

Treatment outcomes in non-occlusive mesenteric ischemia and post-treatment return to social activities.

PURPOSE: To investigate the treatment outcomes of patients with non-occlusive mesenteric ischemia (NOMI) at our institution, we focused on their post-treatment return to social activities. METHODS: This study included patients with suspected NOMI who were referred to our department between 2011 and 2023. In-hospital mortality was also investigated as a prognostic factor. The Glasgow-Pittsburgh Outcome Categories (GPOC) score was used to evaluate the return to social activities. The relationship between in-hospital mortality and GPOC scores and patient background and treatment factors was examined. RESULTS: Eighty-two patients were included in the study. Among them, 54 (65.9%) died during hospitalization. Only 9 patients (11%) returned to their social activities. In the multivariate analysis, non-surgical management was found to be the only independent factor for in-hospital mortality. Positive portal venous gas on computed tomography, no open abdomen, no pre-onset catecholamine administration, platelet count < 100,000/µL, lactate level < 5 mmol/L, APTT < 46 s, and Sequential Organ Failure Assessment score < 11 were factors significantly associated with an increased likelihood of return to social activities. CONCLUSION: This is the first study to assess the post-treatment return to social activities among patients with NOMI. Our findings highlight the concerning reality that survivors may face prolonged dependence on medical care.

Performance of a Large Language Model in Screening Citations.

Importance: Large language models (LLMs) are promising as tools for citation screening in systematic reviews. However, their applicability has not yet been determined. Objective: To evaluate the accuracy and efficiency of an LLM in title and abstract literature screening. Design, Setting, and Participants: This prospective diagnostic study used the data from the title and abstract screening process for 5 clinical questions (CQs) in the development of the Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock. The LLM decided to include or exclude citations based on the inclusion and exclusion criteria in terms of patient, population, problem; intervention; comparison; and study design of the selected CQ and was compared with the conventional method for title and abstract screening. This study was conducted from January 7 to 15, 2024. Exposures: LLM (GPT-4 Turbo)-assisted citation screening or the conventional method. Main Outcomes and Measures: The sensitivity and specificity of the LLM-assisted screening process was calculated, and the full-text screening result using the conventional method was set as the reference standard in the primary analysis. Pooled sensitivity and specificity were also estimated, and screening times of the 2 methods were compared. Results: In the conventional citation screening process, 8 of 5634 publications in CQ 1, 4 of 3418 in CQ 2, 4 of 1038 in CQ 3, 17 of 4326 in CQ 4, and 8 of 2253 in CQ 5 were selected. In the primary analysis of 5 CQs, LLM-assisted citation screening demonstrated an integrated sensitivity of 0.75 (95% CI, 0.43 to 0.92) and specificity of 0.99 (95% CI, 0.99 to 0.99). Post hoc modifications to the command prompt improved the integrated sensitivity to 0.91 (95% CI, 0.77 to 0.97) without substantially compromising specificity (0.98 [95% CI, 0.96 to 0.99]). Additionally, LLM-assisted screening was associated with reduced time for processing 100 studies (1.3 minutes vs 17.2 minutes for conventional screening methods; mean difference, -15.25 minutes [95% CI, -17.70 to -12.79 minutes]). Conclusions and Relevance: In this prospective diagnostic study investigating the performance of LLM-assisted citation screening, the model demonstrated acceptable sensitivity and reasonably high specificity with reduced processing time. This novel method could potentially enhance efficiency and reduce workload in systematic reviews.

Machine-learning model for predicting oliguria in critically ill patients.

This retrospective cohort study aimed to develop and evaluate a machine-learning algorithm for predicting oliguria, a sign of acute kidney injury (AKI). To this end, electronic health record data from consecutive patients admitted to the intensive care unit (ICU) between 2010 and 2019 were used and oliguria was defined as a urine output of less than 0.5 mL/kg/h. Furthermore, a light-gradient boosting machine was used for model development. Among the 9,241 patients who participated in the study, the proportions of patients with urine output < 0.5 mL/kg/h for 6 h and with AKI during the ICU stay were 27.4% and 30.2%, respectively. The area under the curve (AUC) values provided by the prediction algorithm for the onset of oliguria at 6 h and 72 h using 28 clinically relevant variables were 0.964 (a 95% confidence interval (CI) of 0.963-0.965) and 0.916 (a 95% CI of 0.914-0.918), respectively. The Shapley additive explanation analysis for predicting oliguria at 6 h identified urine values, severity scores, serum creatinine, oxygen partial pressure, fibrinogen/fibrin degradation products, interleukin-6, and peripheral temperature as important variables. Thus, this study demonstrates that a machine-learning algorithm can accurately predict oliguria onset in ICU patients, suggesting the importance of oliguria in the early diagnosis and optimal management of AKI.

Usability evaluation of a glove-type wearable device for efficient biometric collection during triage.

To efficiently allocate medical resources at disaster sites, medical workers perform triage to prioritize medical treatments based on the severity of the wounded or sick. In such instances, evaluators often assess the severity status of the wounded or sick quickly, but their measurements are qualitative and rely on experience. Therefore, we developed a wearable device called Medic Hand in this study to extend the functionality of a medical worker's hand so as to measure multiple biometric indicators simultaneously without increasing the number of medical devices to be carried. Medic Hand was developed to quantitatively and efficiently evaluate "perfusion" during triage. Speed is essential during triage at disaster sites, where time and effort are often spared to attach medical devices to patients, so the use of Medic Hand as a biometric measurement device is more efficient for collecting biometric information. For Medic Hand to be handy during disasters, it is essential to understand and improve upon factors that facilitate its public acceptance. To this end, this paper reports on the usability evaluation of Medic Hand through a questionnaire survey of nonmedical workers.

Machine learning algorithm for predicting 30-day mortality in patients receiving rapid response system activation: A retrospective nationwide cohort study.

This study investigated the accuracy of a machine learning algorithm for predicting mortality in patients receiving rapid response system (RRS) activation. This retrospective cohort study used data from the In-Hospital Emergency Registry in Japan, which collects nationwide data on patients receiving RRS activation. The missing values in the dataset were replaced using multiple imputations (mode imputation, BayseRidge sklearn. linear model, and K-nearest neighbor model), and the enrolled patients were randomly assigned to the training and test cohorts. We established prediction models for 30-day mortality using the following four types of machine learning classifiers: Light Gradient Boosting Machine (LightGBM), eXtreme Gradient Boosting, random forest, and neural network. Fifty-two variables (patient characteristics, details of RRS activation, reasons for RRS initiation, and hospital capacity) were used to construct the prediction algorithm. The primary outcome was the accuracy of the prediction model for 30-day mortality. Overall, the data from 4,997 patients across 34 hospitals were analyzed. The machine learning algorithms using LightGBM demonstrated the highest predictive value for 30-day mortality (area under the receiver operating characteristic curve, 0.860 [95 % confidence interval, 0.825-0.895]). The SHapley Additive exPlanations summary plot indicated that hospital capacity, site of incidence, code status, and abnormal vital signs within 24 h were important variables in the prediction model for 30-day mortality.

Usefulness of Endoscopic Retrograde Cholangiopancreatography (ERCP)-Related Procedures for Gallstone Pancreatitis.

INTRODUCTION: Endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic sphincterotomy (EST) are said to be useful procedures for gallstone pancreatitis. However, there have been few reports on a large number of patients to whom they were used. The clinical usefulness of ERCP and EST is herein examined retrospectively. METHODS: ERCP and EST were performed to evaluate their clinical usefulness and safety in 108 patients who had gallbladder stones from December 1985 to October 2017 and were diagnosed as having gallstone pancreatitis. Of 108 patients, 83 were mild, and 25 were severe. Following the procedures, clinical courses were observed for three years in 108 patients who underwent the treatments. RESULTS: Cholangiogram was successfully conducted in 108 patients. Bile duct stones were noted in 90 patients, and the stones were removed after EST. Of 18 patients who did not show bile duct stone in cholangiogram, 13 patients underwent EST, while five patients taking anticoagulants completed procedures only with cholangiogram. Accidental symptom was hemorrhage in three patients (2.7%; 3/108), but it was mild and conservatively resolving. During the three-year observation period, acute cholangitis was noted in three patients (2.7%; 3/108), but no relapsing pancreatitis was noted. CONCLUSIONS: It was suggested that ERCP and EST could be useful therapies for gallstone pancreatitis.

Toward an application of automatic evaluation system for central facial palsy using two simple evaluation indices in emergency medicine.

A stroke is a medical emergency and thus requires immediate treatment. Paramedics should accurately assess suspected stroke patients and promptly transport them to a hospital with stroke care facilities; however, current assessment procedures rely on subjective visual assessment. We aim to develop an automatic evaluation system for central facial palsy (CFP) that uses RGB cameras installed in an ambulance. This paper presents two evaluation indices, namely the symmetry of mouth movement and the difference in mouth shape, respectively, extracted from video frames. These evaluation indices allow us to quantitatively evaluate the degree of facial palsy. A classification model based on these indices can discriminate patients with CFP. The results of experiments using our dataset show that the values of the two evaluation indices are significantly different between healthy subjects and CFP patients. Furthermore, our classification model achieved an area under the curve of 0.847. This study demonstrates that the proposed automatic evaluation system has great potential for quantitatively assessing CFP patients based on two evaluation indices.

Association between hospital spending and in-hospital mortality of patients with sepsis based on a Japanese nationwide medical claims database study.

Background: The effect of hospital spending on the mortality rate of patients with sepsis has not yet been fully elucidated. We hypothesized that hospitals that consume more medical resources would have lower mortality rates among patients with sepsis. Methods: This retrospective study used administrative data from 2010 to 2017. The enrolled hospitals were divided into quartiles based on average daily medical cost per sepsis case. The primary and secondary outcomes were the average in-hospital mortality rate of patients with sepsis and the effective cost per survivor among the enrolled hospitals, respectively. A multiple regression model was used to determine the significance of the differences among hospital categories to adjust for baseline imbalances. Results: Among 997 hospitals enrolled in this study, the crude in-hospital mortality rates were 15.7% and 13.2% in the lowest and highest quartiles of hospital spending, respectively. After adjusting for confounding factors, the highest hospital spending group demonstrated a significantly lower in-hospital mortality rate than the lowest hospital spending group (coefficient = -0.025, 95% confidence interval [CI] -0.034 to -0.015; p < 0.0001). Similarly, the highest hospital spending group was associated with a significantly higher effective cost per survivor than the lowest hospital spending group (coefficient = 77.7, 95% CI 73.1 to 82.3; p < 0.0001). In subgroup analyses, hospitals with a small or medium number of beds demonstrated a consistent pattern with the primary test, whereas those with a large number of beds or academic affiliations displayed no association. Conclusions: Using a nationwide Japanese medical claims database, this study indicated that hospitals with greater expenditures were associated with a superior survival rate and a higher effective cost per survivor in patients with sepsis than those with lower expenditures. In contrast, no correlations between hospital spending and mortality were observed in hospitals with a large number of beds or academic affiliations.

Epidemiology and patterns of empiric antimicrobial therapy practice in patients with community-onset sepsis using data from a Japanese nationwide medical claims database-the Japan Sepsis Alliance (JaSA) study group.

Objectives: We aimed to describe empiric antimicrobial options for patients with community-onset sepsis using nationwide real-world data from Japan. Methods: This retrospective cohort study used nationwide Japanese data from a medical reimbursement system database. Patients aged ≥20 years with both presumed infections and acute organ dysfunction who were admitted to hospitals from the outpatient department or emergency department between 2010 and 2017 were enrolled. We described the initial choices of antimicrobials for patients with sepsis stratified by intensive care unit (ICU) or ward. Results: There were 1,195,741 patients with community-onset sepsis; of these, 1,068,719 and 127,022 patients were admitted to the wards and ICU, respectively. Third-generation cephalosporins and carbapenem were most commonly used for patients with community-onset sepsis. We found that 1.7% and 6.0% of patients initially used antimicrobials for methicillin-resistant Staphylococcus aureus coverage in the wards and ICU, respectively. Although half of the patients initially used antipseudomonal agents, only a few patients used a combination of antipseudomonal agents. Moreover, few patients initially used a combination of antimicrobials to treat methicillin-resistant Staphylococcus aureus and Pseudomonas sp. Conclusion: Third-generation cephalosporins and carbapenem were most frequently used for patients with sepsis. A combination therapy of antimicrobials for drug-resistant bacteria coverage was rarely provided to these patients.

Distinction of Drug-Induced Liver Injury From Autoimmune Hepatitis in Patients With Acute Liver Injury: Proposal of a Combination of Diagnostic Scores.

Background and Aims: Acute liver injury (ALI) due to autoimmune hepatitis (AIH) can be treated by immunosuppression. In contrast, idiosyncratic drug-induced liver injury (DILI) had a poor prognosis. DILI thus needs to be distinguished from non-DILI. Methods: Twenty-nine patients with DILI and 77 with non-DILI (42 of AIH and 35 with undetermined cause) diagnosed during 2005-2017 comprised the derivation cohort. 110 patients with ALI due to either AIH, DILI, or obscure causes at 6 liver centers during 2010-2015 were the validation cohort. Revised international AIH group scores (IAIHGs) and the Roussel-Uclaf Causality Assessment Method (RUCAM) were modified to calculate results using medical interviews and laboratory data without chronological changes. Diagnostic accuracy for the distinction of DILI and non-DILI was evaluated by receiver operating characteristic analysis and results were expressed as the area under the curve (AUC). This study received institutional institutional review board approval (MH2020-205). Results: The AUCs of modified IAIHGs and RUCAM scores for the diagnosis of DILI were 0.96 and 1.00 when cut-off values were set at 3 for the modified RUCAM and 5 for the modified IAIHGs in the derivation cohort. In the validation cohort, the AUCs of modified IAIHGs and RUCAM scores for the diagnosis of DILI were 0.95 and 0.97, respectively. The accuracy of the combination of the modified scores was 81% (89/110). Conclusion: Modified diagnostic scores based on detailed medical interviews and routine laboratory data can distinguish DILI from non-DILI in patients with ALI.

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J-SSCG 2016)

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (JSSCG 2016), a Japanese-specific set of clinical practice guidelines for sepsis and septic shock created jointly by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine, was first released in February 2017 in Japanese. An English-language version of these guidelines was created based on the contents of the original Japanese-language version. Members of the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine were selected and organized into 19 committee members and 52 working group members. The guidelines were prepared in accordance with the Medical Information Network Distribution Service (Minds) creation procedures. The Academic Guidelines Promotion Team was organized to oversee and provide academic support to the respective activities allocated to each Guideline Creation Team. To improve quality assurance and workflow transparency, a mutual peer review system was established, and discussions within eachteam were open to the public. Public comments were collected once after the initial formulation of a clinical question (CQ), and twice during the review of the final draft. Recommendations were determined to have been adopted after obtaining support from a twothirds (>66.6%) majority vote of each of the 19 committee members. A total of 87 CQs were selected among 19 clinical areas, including pediatric topics and several other important areas not covered in the first edition of the Japanese guidelines (J-SSCG 2012). The approval rate obtained through committee voting, in additionto ratings of the strengths of the recommendation and its supporting evidence were also added to each recommendation statement.We conducted meta-analyses for 29 CQs. Thirty seven CQs contained recommendations in the form of an expert consensus due to insufficient evidence. No recommendations were provided for 5 CQs.Based on the evidence gathered, we were able to formulate Japanese-specific clinical practice guidelines that are tailored to the Japanese context in a highly transparent manner. These guidelines can easily be used not only by specialists, but also by non-specialists, general clinicians, nurses, pharmacists, clinical engineers, and other healthcare professionals.