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Methicillin-resistant Staphylococcus spp. present challenges in clinical and veterinary settings because effective antimicrobial agents are limited. Phage-encoded peptidoglycan-degrading enzyme, endolysin, is expected to be a novel antimicrobial agent. The enzymatic activity has recently been shown to be influenced by the linker between functional domains in the enzyme. S6_ORF93 (ORF93) is one of the endolysins derived from previously isolated Staphylococcus giant phage S6. The ORF93 was speculated to have a catalytic and peptidoglycan-binding domain with a long linker. In this study, we examined the influence of linker shortening on the characteristics of ORF93. We produce wild-type ORF93 and the linker deletion mutants using an Escherichia coli expression system. These mutants were designated as ORF93-Δ05, ORF93-Δ10, ORF93-Δ15, and ORF93-Δ20, from which 5, 10, 15, and 20 amino acids were removed from the linker, respectively. Except for the ORF93-Δ20, ORF93 and its mutants were expressed as soluble proteins. Moreover, ORF93-Δ15 showed the highest yield and bacteriolytic activity, while the antimicrobial spectrum was homologous. The cold storage experiment showed a slight effect by the linker deletion. According to our results and other studies, linker investigations are crucial in endolysin development., Competing Interests: The authors declare that no competing interests exist., (Copyright: © 2024 Munetomo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Various risk factors for developing severe coronavirus disease 2019 (COVID-19) have been reported. However, studies on the nutritional-related risk factors are limited. In this study, we investigated the effects of serum zinc deficiency on the severity of COVID-19., Methods: The study included a total of 60 COVID-19 patients who were admitted to Tsuyama Chuo Hospital between March 2020 and April 2021. We divided the patients into two categories based on serum levels of zinc (normal and latent zinc deficiency vs. zinc deficiency [<60 μg/dL]) at the time of diagnosis. Severity of COVID-19 was defined as the most exaggerated disease status during admission. The associations between serum zinc deficiency and the severity of COVID-19 were examined using a logistic regression model adjusted for potential confounders., Results: Patients who required oxygen therapy had a higher prevalence of comorbidities and poorer nutritional status, including zinc deficiency, than those who did not require oxygen therapy. Zinc deficiency was associated with an increased risk of COVID-19 severity, with an adjusted odds ratio of 7.29 (95% confidence interval: 1.70-31.18). This result remained significant in the sensitivity analyses conducted after adjusting for patient background factors., Conclusions: Zinc deficiency at the time of COVID-19 diagnosis is an independent risk factor for severe disease. Our findings need to be validated in external studies., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Background: Understanding the association between the immune response and the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has implications for forthcoming prevention strategies. We evaluated the association between antibody titers and the risk of infection for the general population during the Omicron-dominant phase., Methods: This was a prospective cohort study of residents or people affiliated with institutions in Bizen City, which included 1899 participants. We measured the titers of antibodies against SARS-CoV-2 repeatedly every 2 months from June 2022 to March 2023. Infection status was obtained from self-reported questionnaires and the official registry. We estimated risk ratios (RRs) for infection within 2 months of the date of each antibody measurement with 95% confidence intervals (CIs) based on antibody titer categories and spline functions., Results: Compared with the <2500 arbitrary unit (AU)/mL category, the 2500-5000, 5000-10 000, and ≥10 000 AU/mL categories had adjusted RRs of 0.81 (95% CI, .61-1.08), 0.51 (95% CI, .36-.72), and 0.41 (95% CI, .31-.54), respectively. The spline function showed a nonlinear relationship between antibody titer and risk., Conclusions: Higher antibody titers were associated with a lower risk. We demonstrate the usefulness of measuring an antibody titers to determine the appropriate timing for future prevention strategies., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

We investigated the prevalence and characteristics of Cefazolin inoculum effect (CInE) among clinical MSSA isolates in Japan. Although 35.5 % (39 isolates) were positive for the blaZ gene, none met the phenotypic criteria for CInE. Our findings suggested a very low prevalence of CInE among MSSA isolates in our clinical setting., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Cryptococcus prostatitis is an uncommon manifestation of cryptococcal infection that occurs mostly in immunocompromised patients. Tocilizumab, an anti-interleukin-6 receptor monoclonal antibody, has been associated with an increased risk of cryptococcal infections. However, there have been no documented cases of cryptococcal prostatitis in patients receiving tocilizumab therapy. We report a case of cryptococcal prostatitis in a 72-year-old man treated with glucocorticoids and tocilizumab for giant cell arteritis and granulomatosis with polyangiitis. The patient presented dysuria and his serum level of prostate-specific antigen was elevated. Magnetic resonance imaging revealed a prostate mass, and a prostate biopsy was performed, leading to a pathologic diagnosis of cryptococcal prostatitis. Fungal cultures for blood and urine were negative, while the cryptococcal antigen for both serum and urine showed positive results. There were no particular findings in the pulmonary and central nervous systems. The patient was successfully treated with oral fluconazole (400 mg/day) and was discharged. Although cryptococcal prostatitis is a rare entity, clinicians should note that an immunosuppressed patient may develop such a difficult-to-diagnose disease., Competing Interests: Declaration of competing interest The authors have no conflicts of interest., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Background: We developed a virtual reality (VR) education system and evaluated its clinical utility for promoting hand hygiene practices., Methods: This prospective, 2-week, randomized controlled study conducted at Okayama University Hospital, Japan, from November 2023 to January 2024, involved 22 participants (18 medical students and 4 residents). A fully immersive 360° VR system (VIVE Pro Eye) using a head-mounted display and sensing gloves was used to develop 3 health care tasks in a virtual patient room-Environmental Cleaning, Gauze Exchange, and Urine Collection. After monitoring all participants' baseline usage data of portable hand-rubbing alcohol in the first week, we randomly assigned them into 1:1 groups (VR training and video lecture groups). The primary outcome was differences in hand-rubbed alcohol use before and after intervention., Results: Before the intervention, alcohol use did not significantly differ between both groups. After the intervention, a significant increase in alcohol use was observed in the VR training group (median: 8.2 g vs 16.2 g; P = .019) but not in the video lecture group., Conclusions: Our immersive 360° VR education system enhanced hand hygiene practices. Infection prevention and control practitioners and digital technology experts must collaborate to advance the development of superior educational devices and content., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: We aimed to improve the prognosis, treatment, and management of Staphylococcus aureus bacteremia (SAB) by evaluating the association between adherence to quality indicators (QIs) and clinical outcomes in patients with their clinical outcomes., Methods: We retrospectively collected clinical and microbiological data on hospitalized patients with SAB from 14 hospitals (three with >  600, two with 401-600, five with 201-400, and four with ≤ 200 beds) in Japan from January to December 2022. The SAB management quality was evaluated using the SAB-QI score (ranging from 0 to 13 points), which consists of 13 QIs (grouped into five categories) based on previous literature., Results: Of the 4,448 positive blood culture episodes, 289 patients with SAB (6.5%) were enrolled. The SAB-QI scores ranged from 3 to 13, with a median score of 9 points. The SAB-QI score was highest in middle-sized hospitals with 401-600 beds. Adherence to each of the four QI categories (blood culture, echocardiography, source control, and antibiotic treatment) was significantly higher in survived cases than in fatal cases. Kaplan-Meier curves with log-rank tests demonstrated that higher adherence to SAB-QIs indicated a better prognosis. Logistic regression analysis revealed that age, methicillin resistance, multiple comorbidities (≥ 2), and low SAB-QI score were significantly associated with 30-day mortality in patients with SAB., Conclusions: Our study highlights that greater adherence to the SAB-QIs correlates with improved patient outcomes. Management of patients with SAB should follow these recommended indicators to maintain the quality of care, especially for patients with poor prognosticators., (© 2024. The Author(s).)

This study investigated the correlation between oxidative stress and blood amino acids associated with nitric oxide metabolism in adult patients with coronavirus disease (COVID-19) pneumonia. Clinical data and serum samples were prospectively collected from 100 adult patients hospitalized for COVID-19 between July 2020 and August 2021. Patients with COVID-19 were categorized into three groups for analysis based on lung infiltrates, oxygen inhalation upon admission, and the initiation of oxygen therapy after admission. Blood data, oxidative stress-related biomarkers, and serum amino acid levels upon admission were compared in these groups. Patients with lung infiltrations requiring oxygen therapy upon admission or starting oxygen post-admission exhibited higher serum levels of hydroperoxides and lower levels of citrulline compared to the control group. No remarkable differences were observed in nitrite/nitrate, asymmetric dimethylarginine, and arginine levels. Serum citrulline levels correlated significantly with serum lactate dehydrogenase and C-reactive protein levels. A significant negative correlation was found between serum levels of citrulline and hydroperoxides. Levels of hydroperoxides decreased, and citrulline levels increased during the recovery period compared to admission. Patients with COVID-19 with extensive pneumonia or poor oxygenation showed increased oxidative stress and reduced citrulline levels in the blood compared to those with fewer pulmonary complications. These findings suggest that combined oxidative stress and abnormal citrulline metabolism may play a role in the pathogenesis of COVID-19 pneumonia.

Background/Objectives : Among various carbapenemases, New Delhi metallo-beta-lactamases (NDMs) are recognized as the most powerful type capable of hydrolyzing all beta-lactam antibiotics, often conferring multi-drug resistance to the microorganism. The objective of this review is to synthesize current scientific data on NDM inhibitors to facilitate the development of future therapeutics for challenging-to-treat pathogens. Methods : Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Extension for Scoping Reviews, we conducted a MEDLINE search for articles with relevant keywords from the beginning of 2009 to December 2022. We employed various generic terms to encompass all the literature ever published on potential NDM inhibitors. Results : Out of the 1760 articles identified through the database search, 91 met the eligibility criteria and were included in our analysis. The fractional inhibitory concentration index was assessed using the checkerboard assay for 47 compounds in 37 articles, which included 8 compounds already approved by the Food and Drug Administration (FDA) of the United States. Time-killing curve assays (14 studies, 25%), kinetic assays (15 studies, 40.5%), molecular investigations (25 studies, 67.6%), in vivo studies (14 studies, 37.8%), and toxicity assays (13 studies, 35.1%) were also conducted to strengthen the laboratory-level evidence of the potential inhibitors. None of them appeared to have been applied to human infections. Conclusions : Ongoing research efforts have identified several potential NDM inhibitors; however, there are currently no clinically applicable drugs. To address this, we must foster interdisciplinary and multifaceted collaborations by broadening our own horizons.

Purpose: Ureaplasma urealyticum is a rare pathogen associated with septic arthritis that predominantly affects patients with hypogammaglobulinemia. Bacterial identification of fastidious organisms is challenging because they are undetectable by routine culture testing. To the best of our knowledge, this is the first report of septic arthritis induced by U. urealyticum infection in Japan., Case Description: We describe the case of a 23-year-old Japanese female with secondary hypogammaglobulinemia (serum immunoglobulin level < 500 mg/dL), identified 8 years after treatment with rituximab. The patient presented with persistent fever and polyarthritis that were unresponsive to ceftriaxone and prednisolone. Contrast-enhanced computed tomography and gallium-67 scintigraphy revealed effusion and inflammation in the left sternoclavicular, hip, wrist, knee, and ankle joints. Although Gram staining and bacterial culture of the drainage fluid from the left hip joint were negative, the condition exhibited characteristics of purulent bacterial infection. The patient underwent empirical treatment with doxycycline, and her symptoms promptly resolved. Subsequent 16S ribosomal RNA (rRNA) gene sequencing of the joint fluid confirmed the presence of U. urealyticum, leading to the diagnosis of septic arthritis. Combination therapy with doxycycline and azithromycin yielded a favorable recovery from the inflammatory status and severe arthritic pain., Conclusion: This case highlights U. urealyticum as a potential causative agent of disseminated septic arthritis, particularly in patients with hypogammaglobulinaemia. The 16S rRNA gene analysis proved beneficial for identifying pathogens in culture-negative specimens, such as synovial fluid, in suspected bacterial infections., (© 2024. The Author(s).)

The global pandemic of COVID-19 has underscored the significance of establishing and sustaining a practical and efficient infection control system for the benefit and welfare of society. Infectious disease (ID) specialists are expected to take on leadership roles in enhancing organizational infrastructures for infection prevention and control (IPC) at the hospital, community, and national levels. However, due to an absolute shortage and an uneven distribution, many core hospitals currently lack the ID specialists. Given the escalating global risk of emerging and re-emerging infectious diseases as well as antimicrobial resistance pathogens, the education and training of ID specialists constitutes an imperative concern. As demonstrated by historical changes in the healthcare reimbursement system, the establishment and enhancement of IPC measures is pivotal to ensuring medical safety. The existing structure of academic society-driven certification and training initiatives for ID specialists, contingent upon the discretionary decisions of individual physicians, possesses both quantitative and qualitative shortcomings. In this article, I first address the present situations and challenges related to ID specialists and then introduce my idea of securing ID specialists based on the new concepts and platforms; (i) ID Specialists as National Credentials, (ii) Establishment of the Department of Infectious Diseases in Medical and Graduate Schools, (iii) Endowed ID Educative Courses Funded by Local Government and Pharmaceutical Companies, and (iv) Recruitment of Young Physicians Engaged in Healthcare Services in Remote Areas. As clarified by the COVID-19 pandemic, ID specialists play a crucial role in safeguarding public health. Hopefully, this article will advance the discussion and organizational reform for the education and training of ID specialists., Competing Interests: No potential conflict of interest relevant to this article was reported.

Escherichia coli-associated native-valve infective endocarditis is a rare disease that affects elderly patients with underlying risk factors such as diabetes mellitus, malignancy, and renal failure. Long-term use of calcium polystyrene sulfonate is a potential risk factor for gastrointestinal mucosal damage or even colorectal ulcers. Herein, we describe a fatal case of a 66-year-old Japanese man with diabetes mellitus and renal failure who was prescribed calcium polystyrene sulfonate (CPS) for 11 years and developed a CPS-induced rectal ulcer, leading to E. coli native-valve infective endocarditis. The patient was admitted to our hospital due to acute-onset impaired consciousness. As a result of the systemic investigation, he was diagnosed with E. coli bacteremia accompanied by multiple cerebral infarctions and an acute hemorrhagic rectal ulcer. Transesophageal echocardiography revealed a 20-mm vegetative structure on the mitral valve, resulting in a final diagnosis of E. coli-associated infective endocarditis. After rectal resection, mitral valve replacement surgery was performed; however, the patient died shortly after surgery. Pathological findings of the resected rectum showed deposition of a basophilic crystalline material suggesting the presence of CPS. Our case highlights the potential risk of colorectal ulcers in a long-term CPS user, which can trigger bacterial translocation and endocarditis as fatal complications., (© 2024. The Author(s).)

Depressive disorders are among the leading causes of disability globally. However, information on the burden of depressive disorders in Vietnam is limited. We aimed to analyse the burden of depressive disorders in Vietnam from 1990 to 2019. Using data from the Global Burden of Disease Study 2019, prevalence and disability-adjusted life-years (DALYs) were used as indicators to analyse the burden of depressive disorders by age and sex. In 2019 in Vietnam, depressive disorders comprised 2629.1 thousand (95% uncertainty interval (UI): 2233.3-3155.9) estimated cases and 380.6 thousand (95% UI: 258.9-533.8) estimated DALYs. The crude prevalence rate of depressive disorders was higher among females than among males. The DALYs of depressive disorder accounted for a higher percentage of the total all-cause DALYs in the 10-64-year age group than in other age groups. Major depressive disorder was the largest contributor to the burden of depressive disorders. From 1990 to 2019, the crude prevalence and DALY rates per 100 000 population due to depressive disorders increased significantly, whereas age-standardised rates of prevalence and DALYs decreased significantly; the respective average annual percent changes were 0.88% (95% confidence interval: 0.87 to 0.89), 0.68% (0.66 to 0.70), -0.20% (-0.21 to -0.19), and -0.27% (-0.28 to -0.25). Although the age-standardised prevalence rate was lower than that seen globally, depressive disorders were considerable mental health issues in Vietnam. This study will help governments and policymakers to establish appropriate strategies to reduce the burden of these disorders by identifying the priority areas and individuals., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The persistent ascension of childhood obesity on a global scale constitutes a significant quandary. The prevalence of childhood obesity in Japan peaked in the early 2000s and has been reported to have declined since then, but recent data and its trend including the novel coronavirus disease 2019 (COVID-19) pandemic era are not available. Moreover, there is a dearth of studies examining the correlation between the trend in childhood obesity and exercise habits over the past decade. This study aims to examine the changes in the prevalence of obesity, physical fitness, and exercise habits over the past 10 years in Japanese children. We investigated the prevalence of childhood obesity in Japan, using the School Health Statistics Survey data from 2012 to 2021. The dataset has a sample size representative of children nationwide and includes variables for obesity, such as height, weight, and age. Data were classified into groups by sex and age (6-8, 9-11, and 12-14 years age). Children weighing 20% or more of the standard body weight are classified as obese. The annual percentage changes and average annual percentage changes were estimated using the joinpoint regression model. We also examined the trends in the physical fitness test score and exercise time. Average annual percentage changes of boys increased, especially in the 6- to 8-year age group (3.4%-4.6%). For girls, average annual percentage changes had increased in 6- to 8-year (2.5%-4.0%) and 9- to 11-year (0.9%-2.2%) age groups. Since the late 2010s, significantly increasing annual percentage changes were observed in 12- to 14-year age boys (6.7%-8.9%) and girls of many age groups (2.6%-8.6%). The physical fitness test score and exercise time showed decreasing trends since the late 2010s. Childhood obesity may have generally risen in Japan, in the last decade. Encouraging healthy eating and physical activity through school policies and curricula is necessary., (© 2023 World Obesity Federation.)

Determination of long COVID requires ruling out alternative diagnoses, but there has been no report on the features of alternative diagnoses. This study was a single-center retrospective study of outpatients who visited our clinic between February 2021 and June 2023 that was carried out to determine the characteristics of alternative diagnoses in patients with post-COVID-19 symptoms. In a total of 731 patients, 50 patients (6.8%) were newly diagnosed with 52 diseases requiring medical intervention, and 16 (32%) of those 50 patients (2.2% of the total) were considered to have priority for treatment of the newly diagnosed disorders over long COVID treatment. The proportion of patients with a new diagnosis increased with advance of age, with 15.7% of the patients aged 60 years or older having a new diagnosis. Endocrine and metabolic diseases and hematological and respiratory diseases were the most common, being detected in eight patients (16%) each. Although 35 of the 52 diseases (67%) were related to their symptoms, endocrine and metabolic diseases were the least associated with specific symptoms. Other disorders that require attention were found especially in elderly patients with symptomatic long COVID. Thus, appropriate assessment and differentiation from alternative diagnoses are necessary for managing long COVID., (© 2024. The Author(s).)

Background and Objective: Adverse drug events (ADEs) are becoming a significant public health issue. However, reports on ADE-related mortality are limited to national-level evaluations. Therefore, we aimed to reveal overall trends in ADE-related mortality across the 21st century on an international level., Methods: This observational study analysed long-term trends in ADE-related mortality rates from 2001 to 2019 using the World Health Organization Mortality Database. The rates were analysed according to sex, age and region. North America, Latin America and the Caribbean, Western Europe, Eastern Europe and Western Pacific regions were assessed. Fifty-four countries were included with four-character International Statistical Classification of Disease and Related Health Problems, Tenth Revision codes in the database, population data in the World Population Prospects 2019 report, mortality data in more than half of the study period, and high-quality or medium-quality death registration data. A locally weighted regression curve was used to show international trends in age-standardised rates., Results: The global ADE-related mortality rate per 100,000 population increased from 2.05 (95% confidence interval 0.92-3.18) in 2001 to 6.86 (95% confidence interval 5.76-7.95) in 2019. Mortality rates were higher among men than among women, especially in those aged 20-50 years. The population aged ≥ 75 years had higher ADE-related mortality rates than the younger population. North America had the highest mortality rate among the five regions. The global ADE-related mortality rate increased by approximately 3.3-fold from 2001 to 2019., Conclusions: The burden of ADEs has increased internationally with rising mortality rates. Establishing pharmacovigilance systems can facilitate efforts to reduce ADE-related mortality rates globally., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Introduction: This study aimed to elucidate the prevalence and clinical characteristics of patients with long COVID (coronavirus disease 2019), especially focusing on 50% hemolytic complement activity (CH50)., Methods: This retrospective observational study focused on patients who visited Okayama University Hospital (Japan) for the treatment of long COVID between February 2021 and March 2023. CH50 levels were measured using liposome immunometric assay (Autokit CH50 Assay, FUJIFILM Wako Pure Chemical Corporation, Japan); high CH50 was defined as ≥59 U/mL. Univariate analyses assessed differences in the clinical background, long COVID symptoms, inflammatory markers, and clinical scores of patients with normal and high CH50. Logistic regression model investigated the association between high CH50 levels and these factors., Results: Of 659 patients who visited our hospital, 478 patients were included. Of these, 284 (59.4%) patients had high CH50 levels. Poor concentration was significantly more frequent in the high CH50 group (7.2% vs. 13.7%), whereas no differences were observed in other subjective symptoms (fatigue, headache, insomnia, dyspnea, tiredness, and brain fog). Multivariate analysis was performed on factors that could be associated with poor concentration, suggesting a significant relationship to high CH50 levels (adjusted odds ratio [aOR], 2.70; 95% confidence interval [CI], 1.33-5.49). Also, high CH50 was significantly associated with brain fog (aOR, 1.66; 95% CI, 1.04-2.66)., Conclusions: High CH50 levels were frequently reported in individuals with long COVID, indicating a relationship with brain fog. Future in-depth research should examine the pathological role and causal link between complement immunity and the development of long COVID., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Background: In the global aging, the coronavirus disease 2019 (COVID-19) pandemic may have affected the place of death (PoD) in Japan, where hospital deaths have dominated for decades. We analyzed the PoD trends before and during the COVID-19 pandemic in Japan., Methods: This nationwide observational study used vital statistics based on death certificates from Japan between 1951 and 2021. The proportion of PoD; deaths at home, hospitals, and nursing homes; and annual percentage change (APC) were estimated using joinpoint regression analysis. Analyses were stratified by age groups and causes of death., Results: After 2019, home deaths exhibited upward trends, while hospital death turned into downward trends. By age, no significant trend change was seen in the 0-19 age group, while hospital deaths decreased in the 20-64 age group in 2019. The trend change in home death in the ≥65 age group significantly increased since 2019 with an APC of 12.3% (95% confidence interval [CI]: 9.0 to 15.7), while their hospital death trends decreased by -4.0% (95% CI: -4.9 to -3.1) in 2019-2021. By cause of death, home death due to cancer and the old age increased since 2019 with an APC of 29.3% (95% CI: 25.4 to 33.2) and 8.8% (95% CI: 5.5 to 12.2), respectively., Conclusion: PoD has shifted from hospital to home during the COVID-19 pandemic in Japan. The majority of whom were older population with cancer or old age., Competing Interests: The corresponding author has co-authored with the proposed editors for less than 5 years; however, this does not alter our adherence to the PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Shibata et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Functional hyperthermia (FH) is characterized by hyperthermia resulting from sympathetic hyperactivity rather than inflammation, and it is frequently overlooked by medical practitioners due to the absence of abnormalities in a medical examination. Although FH is an important differential diagnosis for fever of unknown origin (FUO), the literature on FUO cases in Japan lacks information on FH. In this study, we aimed to uncover the population of FH patients hidden in FUO cases. Methods: An outpatient clinic for FUO was established at Okayama University Hospital, and 132 patients were examined during the period from May 2019 to February 2022. Results: A diagnosis of FH was made in 31.1% of the FUO cases, and FH predominantly affected individuals in their third and fourth decades of life with a higher incidence in females (68.3%). The frequency of a history of psychiatric illness was higher in patients with FH than in patients with other febrile illnesses. Although the C-reactive protein (CRP) is generally negative in FH cases, some obese patients, with a body mass index ≥ 25 had slightly elevated levels of CRP but were diagnosed with FH. Conclusions: The results showed the importance of identifying FH when encountering patients with FUO without any organic etiology.

Background: Cryptococcus species can cause severe disseminated infections in immunocompromised hosts. This study investigated the epidemiological features and trends in disseminated cryptococcosis in Japan., Methods: We used publicly available Infectious Diseases Weekly Reports to obtain data on the incidence of disseminated cryptococcosis in Japan from 2015 to 2021. Patient information, including age, sex, and regional and seasonal data, were extracted. The Joinpoint regression program was used to determine the age-adjusted incidence rate (AAR) per 100,000 population, annual percentage change (APC), and average APC (AAPC)., Results: A total of 1047 cases of disseminated cryptococcosis were reported, of which those aged ≥ 70 years accounted for 68.8%. The AAR in men was significantly higher than that in women (median: 0.13 vs. 0.09: p = 0.0024). APC for the overall cases increased by 9.9% (95% confidence interval [95% CI] - 5.4-27.7) from 2015 to 2018 and then decreased by 3.3% (95% CI - 15.5-10.7) from 2018 to 2021. AAPC for the entire study period was 3.1% (95% CI - 1.5-8.0), indicating a possible increase in its number, although not statistically significant. In terms of regional distribution, the average AAR was highest in Shikoku District (0.17) and lowest in Hokkaido District (0.04). Northern Japan exhibited a significantly lower median AAR (median [interquartile range]: 0.06 [0.05, 0.08]) than the Eastern (0.12 [0.12, 0.13]), Western (0.11 [0.10, 0.13]), and Southern (0.14 [0.12, 0.15]) regions. No seasonal variation in incidence was observed., Conclusion: The prevalence of disseminated cryptococcosis has not increased in Japan. Geographically, the incidence is lower in Northern Japan. Further investigations that incorporate detailed clinical data are required., (© 2024. The Author(s).)

In this age of antimicrobial resistance (AMR), improving treatment using existing antibiotics is desirable. Extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales (ESBL-E) are high priority AMR pathogens according to the World Health Organization. Cephamycin-class beta- lactams are tolerant to hydrolysis by ESBL activity and have bactericidal effects on ESBL-E. The aim of the present study was to compare the in vitro minimum inhibitory concentration (MIC) of cefmetazole (CMZ) and flomoxef (FMOX) among ESBL-E strains. This was a retrospective study using microbiology laboratory data from Okayama University Hospital (Japan) from January 2014 to June 2022. The MIC was determined by broth microdilution method and the ESBL phenotypes were determined by double-disk method. Antimicrobial use density (AUD) data for CMZ and FMOX were also gathered. Annual proportions of ESBL-producing organisms in Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae complex were 20.4-30.6%, 3.5-13.7%, and 0-3.1%, respectively. The ESBL-producing bacteria with MIC levels ≤1 μg/mL for CMZ and FMOX ranged from 57 to 84% and 97 to 100%, respectively, for E. coli, and from 50 to 92% and 80 to 100%, respectively, for K. pneumoniae. E. cloacae strains showed MIC levels ≥32 μg/mL for both agents. The AUD ratio for CMZ to FMOX ranged from 5.31 to 12.27, with no apparent upward or downward trend. Proportions of ESBL-producing E. coli and K. pneumoniae strains with MIC ≤1 μg/mL were greater in FMOX than in CMZ. To corroborate the clinical superiority of FMOX in treating ESBL-E infections, a randomized controlled study, as well as pharmacokinetic/pharmacodynamic analysis, is required.