Clostridium butyricum Bacteremia Associated with Probiotic Use, Japan.

Clostridium butyricum, a probiotic commonly prescribed in Asia, most notably as MIYA-BM (Miyarisan Pharmaceutical Co., Ltd.; https://www.miyarisan.com), occasionally leads to bacteremia. The prevalence and characteristics of C. butyricum bacteremia and its bacteriologic and genetic underpinnings remain unknown. We retrospectively investigated patients admitted to Osaka University Hospital during September 2011-February 2023. Whole-genome sequencing revealed 5 (0.08%) cases of C. butyricum bacteremia among 6,576 case-patients who had blood cultures positive for any bacteria. Four patients consumed MIYA-BM, and 1 patient consumed a different C. butyricum-containing probiotic. Most patients had compromised immune systems, and common symptoms included fever and abdominal distress. One patient died of nonocclusive mesenteric ischemia. Sequencing results confirmed that all identified C. butyricum bacteremia strains were probiotic derivatives. Our findings underscore the risk for bacteremia resulting from probiotic use, especially in hospitalized patients, necessitating judicious prescription practices.

Long-acting antiretroviral therapy effectiveness and patient satisfaction using patient questionnaires: data from a real-world setting.

BACKGROUND: Antiretroviral therapy (ART) for HIV infection has evolved substantially. The development of long-acting drugs, such as cabotegravir (CAB) and rilpivirine (RPV) might improve treatment satisfaction among people living with HIV (PLWH). The real-world effectiveness of long-acting ART and its effect on patient satisfaction needs to be assessed. This study investigated antiviral effectiveness and treatment satisfaction in PLWH who switched from conventional to long-acting ART (CAB + RPV). METHODS: This prospective cohort study included PLWH aged 18 years and older who switched to CAB + RPV and received the injections every 8 weeks between June 2022 and May 2023, after a 4-week oral lead-in phase. The eligibility criteria included viral suppression, absence of hepatitis B virus (HBV) DNA, and no prior RPV resistance mutations. Clinical data, including renal, lipid, and glucose biomarker levels, were monitored from the baseline to 44 weeks after switching. Treatment satisfaction was assessed using the HIV Treatment Satisfaction Questionnaire. A linear mixed-effects model was used to estimate changes in clinical data from baseline. RESULTS: Thirty-eight male participants were enrolled. Some participants had detectable levels of viral replication; however, all participants maintained viral suppression (HIV-RNA < 50 copies/mL) at 44 weeks and no cases of virological failure were detected. The creatinine level decreased by - 0.04 mg/dL (95% confidence interval [CI]: - 0.07 to - 0.01), lipid and glucose profiles remained stable, and treatment satisfaction increased by 6.6 points (95% CI: 2.4 to 10.8) after switching to CAB + RPV. CONCLUSIONS: Long-acting ART provides effective viral suppression and enhances treatment satisfaction in PLWH switching from conventional ART. Long-acting ART can improve patient well-being; however, patient selection and monitoring to prevent HBV-related complications are important.

Ruthenibacterium lactatiformans isolated from a human blood culture: a first report.

BACKGROUND: Ruthenibacterium lactatiformans, a Gram-stain-negative, rod-shaped, obligate anaerobic bacterium of the Oscillospiraceae family, has not been previously reported in human infections. This study reports the first case of bacteraemia and potential vertebral osteomyelitis caused by Ruthenibacterium lactatiformans. CASE PRESENTATION: An 82-year-old man with a history of diabetes, chronic renal failure, and prior spinal surgery for spondylolisthesis and spinal stenosis presented with fever and lower back pain. Magnetic resonance imaging revealed multiple vertebral osteomyelitis lesions. Initial blood cultures identified methicillin-resistant Staphylococcus aureus (MRSA), which prompted vancomycin treatment. However, repeated blood cultures not only confirmed persistent MRSA, but also detected Gram-negative bacilli (GNB). Despite surgical removal of the spinal hardware and antimicrobial therapy, the patient's osteomyelitis worsened, necessitating transfer for further management. Subsequent analysis using 16S rRNA gene sequencing identified the GNB as Ruthenibacterium lactatiformans. CONCLUSIONS: This is the first documented instance of human infection with Ruthenibacterium lactatiformans, signifying its pathogenic potential in vertebral osteomyelitis. The involvement of anaerobic bacteria and the possibility of polymicrobial infections complicate the diagnosis and treatment of vertebral osteomyelitis. This report underscores the need for caution when identifying the causative organism and selecting an appropriate treatment.

COVID-19 severity and corticosteroid treatment have minimal effect on specific antibody production.

BACKGROUND: Dexamethasone is currently administered for Coronavirus disease 2019(COVID-19); however, there are concerns about its effect on specific antibodies' production. The aim of this study was to evaluate whether specific antibodies were affected by COVID-19 severity and corticosteroid treatment. METHODS: Of 251 confirmed COVID-19 patients admitted to our hospital between January 26 and August 10, 2020, the early period of the pandemic, 75 patients with sera within 1 month of onset and 1 month or longer were included in the research. A total of 253 serum samples from these patients were collected. The levels of specific antibodies for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2), immunoglobulin G (IgG) and M (IgM), were measured retrospectively. The results were compared separately of each COVID-19 severity, and with or without corticosteroid treatment. RESULTS: Among the 75 patients, 47, 18, and 10 had mild, moderate, and severe disease, respectively. The median age was 53.0 years and 22 (29%) were women. The most common comorbidities were hypertension and dyslipidemia. Corticosteroids were administered to 20 (27%) and 10 (53%), patients with moderate and severe disease, respectively. The positivity rates IgM increased first, and IgG was almost always positive after day 16, regardless of the severity of COVID-19. On days 6-10, both IgG and IgM positivity rates were higher in patients with moderate disease than in those with mild or severe disease. In patients with moderate disease, IgG positivity was similar over time, regardless of corticosteroid treatment. CONCLUSIONS: In COVID-19 patients, specific IgG is positive and maintained for a long period of time, even after corticosteroid treatment. The effect of corticosteroid treatment in a COVID-19 epidemiological study using specific IgG antibodies was considered minor. COVID-19 patients were more likely to receive oxygen if IgM was positive 1 week after onset, but not mechanical ventilation. IgM measurement 1 week after onset may predict COVID-19 severity.

Epidemiological Analysis of Legionella Pneumonia in Japan: A National Inpatient Database Study.

BACKGROUND: Legionella pneumonia, a severe form of pneumonia, is caused by Legionella bacteria. The epidemiology of Legionnaires' disease in Japan, including seasonal trends, risk factors for severe disease, and fatality rates, is unclear. This study examined the epidemiology of Legionella pneumonia in Japan. METHODS: This retrospective cohort study included data of adult patients hospitalized for Legionella pneumonia (identified using the International Classification of Diseases, 10th revision code, A481) in the Japanese Diagnosis Procedure Combination inpatient database, from April 2011 to March 2021. We performed multivariable logistic regression analysis to explore the prognostic factors of in-hospital mortality. RESULTS: Of 7,370 enrolled hospitalized patients from 1,140 hospitals (male, 84.4%; aged >50 years, 87.9%), 469 (6.4%) died during hospitalization. The number of hospitalized patients increased yearly, from 658 in 2016 to 975 in 2020. Multivariable logistic regression analysis revealed that higher in-hospital mortality was associated with older age, male sex, lower body mass index, worsened level of consciousness, comorbidities (congestive heart failure, chronic renal diseases, and metastasis), hospitalization from November to May, and ambulance use. However, lower in-hospital mortality was associated with comorbidity (liver diseases), hospitalization after 2013, and hospitalization in hospitals with higher case volume. CONCLUSION: The characterized epidemiology of Legionella pneumonia in Japan revealed a high mortality rate of 6.4%. To the best of our knowledge, this is the first study to demonstrate a higher mortality rate in winter and in patients with congestive heart failure and metastasis. Further research is needed to understand the complex interplay between the prognostic factors of Legionella pneumonia.

Exploring the efficacy of routine antimicrobial therapy in severe fever with thrombocytopenia syndrome: Overlap weighting analysis using a nationwide inpatient database.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an infectious disease that presents a formidable challenge due to the absence of established therapeutic strategies that are explicitly tailored to its management. This study aimed to assess the impact of routine antimicrobial therapy on patients diagnosed with SFTS in Japan. We conducted a comprehensive retrospective cohort analysis using extensive data from a national inpatient database. METHODS: This study scrutinized data from adult patients with SFTS and categorized them based on whether they received antimicrobial treatment within the initial 2 days of hospital admission. A meticulous evaluation was carried out on a range of outcomes, such as in-hospital mortality rates, overall costs associated with hospitalization, and length of hospital stay. Overlap weighting was applied along with multivariate regression models to enhance the reliability of the findings through confounder adjustment. The outcomes showed no significant improvement in the prognosis of patients with SFTS who received routine antimicrobial therapy. The use of antimicrobials did not yield statistically significant improvements in in-hospital mortality rates or other secondary outcomes, suggesting that such therapeutic interventions may not be necessary during the early stages of hospital admission. CONCLUSION: In our study, administration of antimicrobials within 2 days of admission for SFTS did not affect prognosis. The standard use of antimicrobial treatments may be an issue that should be reconsidered.

Symptoms of post COVID-19 condition and diseases/conditions diagnosed after COVID-19 in Japanese patients: A real-world study using a claims database.

BACKGROUND: More than 200 symptoms of post coronavirus disease (COVID-19) condition (PCC) impacting patients' quality of life have been reported. This study describes the symptoms of well-known PCC and diseases/conditions diagnosed after COVID-19 and analyzes the trends in well-known PCC according to the epidemic waves in the Japanese population. METHODS: Patients with a COVID-19 diagnosis in the JMDC claims database were matched 1:1 with individuals without COVID-19 diagnosis (controls) based on sex, year and month of birth, and risk factors for aggravation. The first month of COVID-19 diagnosis from January 2020-March 2022 was the index month, and the observation period was from July 2019 to 6 months from the index month (patients) and July 2019-September 2022 (controls). RESULTS: Of 263,456 each of patients and controls after matching, 51.8 % were aged 18-49 years, 56.3 % were male, and 24.5 % had risk factors for aggravation. One in 18 patients experienced well-known PCC 2-3 months after severe acute respiratory syndrome cornonavirus 2 infection, with the highest odds ratio (OR) being for pulmonary thromboembolism (29.37), followed by smell/taste disorder (13.34) and respiratory failure (8.28). Some of the common diseases/conditions diagnosed after COVID-19 comprised those of the genitourinary system, eye and adnexa, and ear and mastoid process and certain infectious and parasitic diseases. Overall, the risk difference decreased from the first to the sixth wave, but the OR was >1.00 for most symptoms even during the sixth wave. CONCLUSIONS: PCC symptoms showed a declining trend over time but persisted. Physicians and patients need to recognize PCC symptoms.

Cross-sectional surveillance study of long COVID in Toyonaka city, Osaka prefecture, Japan.

BACKGROUND: As the COVID-19 epidemic continues, concerns about long-term health impacts, specifically long COVID, persist. While the prevalence and symptomatology of long COVID have been explored in various global contexts, large-scale cohort studies in Japan remain limited, especially after the advent of the Omicron variant. METHODS: In this observational study, 4,047 residents with a history of COVID-19 living in Toyonaka City, Osaka Prefecture, were assessed for long COVID symptoms using the VOICE mobile application and a paper survey. Respondents provided demographic and health information, as well as information regarding COVID-19 infection and subsequent symptoms. A Cox proportional hazard regression model was used to estimate the multivariable-adjusted hazard ratios and 95 % confidence intervals for overall morbidity of long COVID symptoms. RESULTS: The survey found that 5.2 % of participants reported the persistence of one or more symptoms at 30 days post-onset. Fatigue was the most commonly reported symptom (1.75 %), followed by hair loss (1.41 %), and cough (1.28 %). Factors associated with an increased risk of experiencing long COVID symptoms included BMI, severe illness during the acute phase, and infection with certain COVID-19 variant strains, including Alpha, Delta, and Omicron. However, the incidence rate of long COVID appears to be decreasing with the dominance of the Omicron variant. CONCLUSIONS: This large-scale study from Toyonaka City suggests a 5.2 % prevalence rate for persistent COVID-19 symptoms 4 weeks post-infection, potentially indicating a lower prevalence of long COVID in Japanese populations after the rise of the Omicron variant.

Association between post-COVID-19 conditions and male semen quality in Japan: A descriptive investigation.

Some reports suggest that coronavirus disease 2019 (COVID-19) may affect male reproductive function. There is also concern in Japan that COVID-19 may contribute to the pre-existing decline in male fertility; however, no studies have investigated the effects of COVID-19 on male reproductive function. In this study, we aimed to analyze the semen quality of men who had recovered from COVID-19. Male patients who had recovered from COVID-19 between February 2020 and September 2021 were recruited for this study. Participants were sent a semen collection kit; they were asked to collect semen at home and deliver it to a laboratory at Osaka University. We used these samples to analyze sperm concentration, total sperm count, and semen volume. In total, 125 participants were included in this study. The median age of all patients was 46 years (interquartile range (IQR): 38-52 years). The severity of COVID-19 was mild in 80 patients; 19 were moderate I, 22 were moderate II, and four were severe. The median semen volume was 2.5 mL (IQR: 1.8-3.1), the median sperm concentration was 98.9 million/mL (IQR: 43.8-162.2), and the median total sperm count was 212.1 million (IQR: 89.7-368.2). In a previous study in Japan, the median sperm count in adult men was reported to be 201 million. Participants in our study did not have lower sperm counts than this, despite their older age. Our results suggest that the long-term effects of COVID-19 on spermatogenesis are minimal.

Epidemiology of post-COVID conditions beyond 3 years and factors associated with their persistence longer than 2 years: A cross-sectional study.

OBJECTIVE: This study aimed to investigate the epidemiology of post-coronavirus disease 2019 (COVID-19) conditions (PCCs) beyond 3 years and identify factors associated with their persistence longer than 2 years. STUDY DESIGN: Cross-sectional questionnaire-based survey. METHODS: We surveyed patients who had recovered from COVID-19 and visited our institution from February 2020 to November 2021. Demographic and clinical data and information on the presence and duration of PCCs were obtained. We identified factors associated with the persistence of PCCs longer than 2 years using multivariate linear regression analyses. RESULTS: Among 935 patients surveyed, 407 completed the survey. Among them, 360 patients had mild disease in the acute phase. The proportions of participants with at least one symptom at 1, 2, and 3 years after symptom onset or COVID-19 diagnosis were 33.2%, 29.8%, and 5.7%, respectively. The numbers of participants with and without any residual symptoms 2 years after the onset of COVID-19 were 87 and 193, respectively. After multivariate adjustment, persistence of PCCs longer than 2 years was associated with lower body mass index, presence of any underlying medical conditions, and number of symptoms lasting for more than 1 month ≥ 5. CONCLUSIONS: The prevalence of PCCs decreased 2 years after symptom onset or COVID-19 diagnosis. We also identified factors associated with PCC persistence longer than 2 years, which could help primary care physicians and patients with PCCs predict the duration of PCCs and better understand their natural history, thus reducing patients' anxiety about their duration.

Oral mouthwashes for asymptomatic to mildly symptomatic adults with COVID-19 and salivary viral load: a randomized, placebo-controlled, open-label clinical trial.

BACKGROUND: Recent randomized clinical trials suggest that the effect of using cetylpyridinium chloride (CPC) mouthwashes on the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load in COVID-19 patients has been inconsistent. Additionally, no clinical study has investigated the effectiveness of on-demand aqueous chlorine dioxide mouthwash against COVID-19. METHODS: We performed a randomized, placebo-controlled, open-label clinical trial to assess for any effects of using mouthwash on the salivary SARS-CoV-2 viral load among asymptomatic to mildly symptomatic adult COVID-19-positive patients. Patients were randomized to receive either 20 mL of 0.05% CPC, 10 mL of 0.01% on-demand aqueous chlorine dioxide, or 20 mL of placebo mouthwash (purified water) in a 1:1:1 ratio. The primary endpoint was the cycle threshold (Ct) values employed for SARS-CoV-2 salivary viral load estimation. We used linear mixed-effects models to assess for any effect of the mouthwashes on SARS-CoV-2 salivary viral load. RESULTS: Of a total of 96 eligible participants enrolled from November 7, 2022, to January 19, 2023, 90 were accepted for the primary analysis. The use of 0.05% CPC mouthwash was not shown to be superior to placebo in change from baseline salivary Ct value at 30 min (difference vs. placebo, 0.640; 95% confidence interval [CI], -1.425 to 2.706; P = 0.543); 2 h (difference vs. placebo, 1.158; 95% CI, -0.797 to 3.112; P = 0.246); 4 h (difference vs. placebo, 1.283; 95% CI, -0.719 to 3.285; P = 0.209); 10 h (difference vs. placebo, 0.304; 95% CI, -1.777 to 2.385; P = 0.775); or 24 h (difference vs. placebo, 0.782; 95% CI, -1.195 to 2.759; P = 0.438). The use of 0.01% on-demand aqueous chlorine dioxide mouthwash was also not shown to be superior to placebo in change from baseline salivary Ct value at 30 min (difference vs. placebo, 0.905; 95% CI, -1.079 to 2.888; P = 0.371); 2 h (difference vs. placebo, 0.709; 95% CI, -1.275 to 2.693; P = 0.483); 4 h (difference vs. placebo, 0.220; 95% CI, -1.787 to 2.226; P = 0.830); 10 h (difference vs. placebo, 0.198; 95% CI, -1.901 to 2.296; P = 0.854); or 24 h (difference vs. placebo, 0.784; 95% CI, -1.236 to 2.804; P = 0.447). CONCLUSIONS: In asymptomatic to mildly symptomatic adults with COVID-19, compared to placebo, the use of 0.05% CPC and 0.01% on-demand aqueous chlorine dioxide mouthwash did not lead to a significant reduction in SARS-CoV-2 salivary viral load. Future studies of the efficacy of CPC and on-demand aqueous chlorine dioxide mouthwash on the viral viability of SARS-CoV-2 should be conducted using different specimen types and in multiple populations and settings.

Aneurysm Infection Caused by Desulfovibrio desulfuricans.

An 84-year-old man in Japan who had undergone endovascular aortic repair 9 years earlier had an infected aneurysm develop. We detected Desulfovibrio desulfuricans MB at the site. The patient recovered after surgical debridement, artificial vessel replacement, and appropriate antimicrobial therapy. Clinicians should suspect Desulfovibrio spp. infection in similar cases.

We Should Pay More Attention to Sex Differences to Predict the Risk of Severe COVID-19: Men Have the Same Risk of Worse Prognosis as Women More Than 10 Years Older.

BACKGROUND: Prioritization for novel coronavirus disease 2019 (COVID-19)-related health policies usually considers age and certain other characteristics, but sex is rarely included, despite the higher risk of severe disease in men. The aim of this study was to compare the impact of sex and age on the severity of COVID-19 by estimating the age difference in years for which the risk for men versus women is the same. METHODS: We analyzed 23,414 Japanese COVID-19 inpatients aged 20-89 years (13,360 men and 10,054 women). We graded the severity of COVID-19 (0 to 5) according to the most intensive treatment required during hospitalization. The risk of grade 2/3/4/5 (non-invasive positive pressure ventilation/invasive mechanical ventilation/extracorporeal membrane oxygenation/death), grade 3/4/5, and separately grade 5 was analyzed using a multiple logistic regression model. RESULTS: The odds ratio (OR) of grades 2/3/4/5, 3/4/5 (primary outcome), and 5 for men relative to women was 2.76 (95% CI, 2.44-3.12), 2.78 (95% CI, 2.42-3.19), and 2.60 (95% CI, 2.23-3.03), respectively, after adjustment for age and date of admission. These risks for men were equivalent to those for women 14.1 (95% CI, 12.3-15.8), 11.2 (95% CI, 9.7-12.8), and 7.5 (95% CI, 6.3-8.7) years older, respectively. CONCLUSION: The risks of worse COVID-19 prognosis (grades 3/4/5) in men were equivalent to those of women 11.2 years older. Reanalyzing data extracted from four previous studies also revealed a large impact of sex difference on the severity of COVID-19. We should pay more attention to sex differences to predict the risk of COVID-19 severity and to formulate public health policy accordingly.

Preserved SARS-CoV-2 neutralizing IgG activity of in-house manufactured COVID-19 convalescent plasma.

PURPOSE: In the current study, we aimed to evaluate the neutralizing IgG activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as well as the coagulation factors of convalescent plasmas which we manufactured in-house without a fast-freezing technique. METHODS: We collected plasmas from eligible participants who had confirmed certain titers of neutralizing antibodies. The plasmas were frozen and stored in the ordinary biofreezer without a fast-freezing function. The purified-IgG neutralizing activity of 20 samples from 19 participants and the coagulation factors of 49 samples from 40 participants were evaluated before and after freezing. RESULTS: Purified-IgG maintained its neutralizing activities, with the median 50 % inhibitory concentration (IC50) of 10.11 mg/ml (IQR 6.53-18.19) before freezing and 8.90 m g/ml (IQR 6.92-28.27) after thawing (p = 0.956). On the contrary, fibrinogen and factor Ⅷ decreased significantly after freezing and thawing in our environment. No significant temperature deviation was observed during the storage period. CONCLUSION: Neutralizing IgG activity, which largely contributes to the antiviral activity of convalescent plasma, did not change through our in-house manufacturing, without fastfreezing and storage conditions for more than 200 days. Ordinary freezers without the fast-freezing function are suitable enough to manufacture and store convalescent plasmas. Hospitals or facilities without specified resources could easily collect and store convalescent plasmas in case of upcoming emerging or re-emerging infectious diseases on-demand with appropriate neutralizing antibody levels measurements.

The safety of plasma apheresis from donors recovering from COVID-19 infection in Japan.

PURPOSE: Since 2020, the novel coronavirus infection (COVID-19) has spread globally. A few studies have investigated the safety of COVID-19 convalescent plasma (CCP) apheresis from COVID-19. This study was the first retrospective observational study of CCP in Japan. METHODS: We recruit donors from April 2020 to November 2021 and plasmapheresis in our center (NCGM: national center for global health and medicine). We set the primary endpoint as the Donors Adverse Event (DAE) occurrence at the time of the CCP collection. Variable selection was used to explore the determinants of DAE. RESULTS: Mean and SD age was 50.5 (10.6) years old. Seventy-three (42.2 %) were female, and 87 (33.3 %) were multiple-times donors. Twelve (6.97 % by donors and 4.6 % in total collections) adverse events occurred. The DAEs were VVR (Vaso Vagal Reaction), paresthesia, hypotension, agitation, dizziness, malaise, and hearing impairment/paresthesia. Half of them were VVR during apheresis. DAE occurred only in first-time donors and more in severe illnesses such as using ventilation and ECMO. From the donor characteristics and variable selection, the risk factors are as follows: younger age, female, the severity of disease at the time of the disease, and lower SBP before initiation. Our DAE incidence did not differ from previous studies. DAEs were more likely to occur in CCP apheresis than in healthy donors. CONCLUSION: We confirm the safety of CCP apheresis in this study, although DAEs were more than healthy donors. More caution should be exercised in the plasma collection for future outbreaks of emerging infectious diseases.

Establishment and clinical application of SARS-CoV-2 catch column.

BACKGROUND: A certain number of patients with coronavirus disease 2019 (COVID-19), particularly those who test positive for SARS-CoV-2 in the serum, are hospitalized. Further, some even die. We examined the effect of blood adsorption therapy using columns that can eliminate SARS-CoV-2 on the improvement of the prognosis of severe COVID-19 patients. METHODS: This study enrolled seven patients receiving mechanical ventilation. The patients received viral adsorption therapy using SARS-catch column for 3 days. The SARS-catch column was developed by immobilizing a specific peptide, designed based on the sequence of human angiotensin-converting enzyme 2 (hACE2), to an endotoxin adsorption column (PMX). In total, eight types of SARS-CoV-2-catch (SCC) candidate peptides were developed. Then, a clinical study on the effects of blood adsorption therapy using the SARS-catch column in patients with severe COVID-19 was performed, and the data in the present study were compared with historical data of severe COVID-19 patients. RESULTS: Among all SCC candidate peptides, SCC-4N had the best adsorption activity against SARS-CoV-2. The SARS-catch column using SCC-4N removed 65% more SARS-CoV-2 than PMX. Compared with historical data, the weaning time from mechanical ventilation was faster in the present study. In addition, the rate of negative blood viral load in the present study was higher than that in the historical data. CONCLUSION: The timely treatment with virus adsorption therapy may eliminate serum SARS-CoV-2 and improve the prognosis of patients with severe COVID-19. However, large-scale studies must be performed in the future to further assess the finding of this study (jRCTs052200134).

Steroid pulse therapy for severe fever with thrombocytopenia syndrome patients may not improve prognosis: Retrospective analysis with overlap weighting using a national inpatient database.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease caused by the SFTS virus. Effective treatment for SFTS has not been established, but steroid pulse therapy is often used. This study aimed to verify whether steroid pulse therapy for SFTS improves prognosis or not. METHODS: Data of SFTS patients were obtained from the Japanese Diagnosis Procedure Combination Database from April 2013 to March 2021. Patients treated with steroid pulse therapy were compared with untreated patients, using overlap weighting and traditional multivariable regression analysis to evaluate the impact of steroid pulse therapy on prognosis. RESULTS: 412 SFTS patients were included in this study, and 66 (16%) underwent steroid pulse therapy within 3 days of admission and were allocated to the steroid pulse therapy group. After overlap weighting, patients in the steroid pulse therapy group had a significantly higher in-hospital mortality rate than patients in the control group (31.1% vs. 20.5%; difference: +10.6%; 95% confidence interval: +2.2% to +19.0%). There were no statistically significant differences in hospitalization cost and length of hospital stay between the two groups. The results of the sensitivity analysis using traditional multivariable regression were similar to those of the main analysis. CONCLUSION: In the analysis of SFTS patients using the Japanese Diagnosis Procedure Combination inpatient data, steroid pulse therapy did not improve patient prognosis. The evidence does not support the universal use of steroid pulse therapy in patients with severe SFTS.

Deprescribing antacids after the diagnosis of Clostridioides difficile infection: A single-center observational study.

Overuse of antacids is associated with the development and recurrence of Clostridioides difficile infection (CDI). Discontinuation of unnecessary antacids for CDI management is advocated; however, the clinical pervasiveness on the discontinuation of antacids remains unclear. We conducted a single-center retrospective observational study to determine the rate of antacid discontinuation following CDI diagnosis. Among 51 patients (58 infections; median age 76.5 years, range 69-82; 53.5% women) treated with antimicrobials against C. difficile, 41 had been treated with antacids, and of these, 18 exhibited no indication for antacid administration. However, none had discontinued antacid use. While CDI provides an opportunity for antacid stewardship, it is not implemented in clinical practice. In addition to the efforts of individual clinicians, the dissemination of knowledge of the indications and side effects of antacids, establishment of a multidisciplinary support system, and creation and implementation of a clinical stewardship pathway are necessary to increase the deprescription of antacids in patients with CDI.

Comparison of the clinical characteristics and outcomes of Japanese patients with COVID-19 treated in primary, secondary, and tertiary care facilities.

AIM: To compare the characteristics and clinical course of patients with coronavirus disease (COVID-19) according to the healthcare level of the admitted hospital, to provide an insight into determining the appropriate level of care for each patient. METHODS: This retrospective, observational study utilized data from the COVID-19 Registry Japan (COVIREGI-JP), the largest Japanese registry of hospitalized patients with COVID-19. Datasets were obtained from reports filed as of May 31, 2022. RESULTS: A total of 59,707 patients (2004 in the primary care group, 41,420 in the secondary care group, and 16,283 in the tertiary care group) from 585 facilities were included in the analysis. Patients with established risk factors for severe disease, such as old age and the presence of comorbidities, were treated at higher care facilities and had poorer initial conditions and in-hospital clinical course, as well as higher mortality. Analysis of the fatality rates for each complication suggested that patients with complications requiring procedures (e.g. pleural effusions, myocardial ischemia, and arrhythmia) may have better survival rates in facilities with specialist availability. The number of deaths and severe COVID-19 cases in this study were notably less than those reported overseas. CONCLUSION: Our results showed that more difficult COVID-19 cases with poor outcomes were treated at higher care level facilities in Japan. Attending to possible complications may be useful for selecting an appropriate treatment hospital. Healthcare providers need to maintain a broad perspective on the distribution of medical resources.

Analysis of cross-reactivity among flaviviruses using sera of patients with dengue showed the importance of neutralization tests with paired serum samples for the correct interpretations of serological test results for dengue.

Dengue is a febrile illness caused by the dengue virus (DENV) that belongs to the genus Flavivirus in the family Flaviviridae. Cross-reactivity between flaviviruses poses a challenge while interpreting serological test results. In the present study, the cross-reactivity of sera of the patients with dengue, who traveled from Japan to DENV-endemic countries, was analyzed by using an enzyme-linked immunosorbent assay (ELISA) and neutralization test (NT). Sixteen serum samples were collected from patients with dengue and were tested for: i) IgM antibodies against Zika virus (ZIKV), West Nile virus (WNV), Japanese encephalitis virus (JEV), and tick-borne encephalitis virus (TBEV) using IgM ELISA, ii) IgG antibody against TBEV using IgG ELISA, and iii) neutralizing antibody against ZIKV, WNV, TBEV, and JEV. Among the 16 samples tested using ELISA, seven samples were IgM-positive for at least one of the other flaviviruses, and nine samples were IgG-positive for TBEV. Neutralizing antibody titers (NATs) against ZIKV, WNV, and TBEV were one-fourth or lower than those against the causative DENV in all samples. The NATs against JEV were one-fourth or lower than those against the causative DENV in six convalescent-phase serum sample among the seven convalescent-phase serum samples. The NAT against DENV of the residual one convalescent-phase serum was similar to that against JEV and that against JEV of its relevant acute-phase serum sample. These results showed that NTs with paired serum samples are important to correctly interpret the serological test results for DENV.