Local radiotherapy for chemotherapy-refractory Kaposi's sarcoma in an HIV-infected patient: A case report and literature review.

Human immunodeficiency virus-associated Kaposi's sarcoma (HIV-KS) is a well-documented vascular tumor with a pathogenesis involving human herpesvirus-8 (HHV-8) infection. While antiretroviral therapy (ART) and chemotherapy are effective for treating most KS cases, some become refractory. In this report, we present a case of a 58-year-old man with refractory HIV-KS treated with ART and chemotherapy. Chemotherapy was eventually discontinued due to an adverse reaction, and the patient presented with painful plantar lesions that impaired ambulation. With the exclusion of visceral metastases, localized radiotherapy was administered, which resulted in significant cosmetic and functional improvements. The patient regained ambulation and lived independently, receiving additional radiotherapy as needed. This case underscores the potential use of radiotherapy for the treatment of ART-resistant KS, particularly when the patient is unresponsive to conventional chemotherapy. It also highlights the need for future research in this area.

Development of a partnership between academia, community, and government in response to the 2022 mpox outbreak in Japan.

Objectives　In response to the steady rise in the number of cases of mpox in nonendemic countries, starting with an outbreak in the United Kingdom in May 2022, the World Health Organization declared a public health emergency of international concern on July 23, 2022. As of November 13, 2022, seven cases of mpox have been reported in Japan.Methods　A community engagement approach was applied to prevent the spread of mpox in Japan.Results　A tripartite partnership between academia, community, and government (ACG) was established to promote multisectoral communication between vulnerable communities, medical personnel involved in diagnosis and treatment, public health specialists at public health centers, epidemiologists at the National Institute of Infectious Diseases (NIID), and government and public administration. Through information sharing, this ACG partnership can translate accurate information into effective infection control measures.Conclusion　By developing and maintaining the ACG partnership, an environment will be created that allows an immediate response to future public health crises affecting vulnerable communities. This Practice Report describes the process of establishing an ACG partnership.

Large-scale resurgence of herpangina in Japan, following the easing of COVID-19 measures.

Objectives: This study examined the rise in herpangina cases and its demographic trends in Japan post-easing of COVID-19 restrictions in the summer of 2023, assessing its potential strain on pediatric healthcare. Methods: Weekly herpangina cases data from the National Institute of Infectious Diseases from 2017 to 2023 were analyzed using difference-in-differences methodology and Poisson regression models, incorporating variables such as time, the COVID-19 pandemic, and the easing of measures. Statistical significance was set at a two-sided P-value of 0.05. Results: A significant increase in herpangina cases was observed from the 19th to the 27th week of 2023, with a notable shift in age distribution compared to that of pre-pandemic years. Poisson regression analysis revealed a positive correlation between the number of herpangina cases and the easing of infection control measures. There was an increase in other respiratory illnesses, including respiratory syncytial virus, particularly in children aged 3 and above. Conclusion: We found a surge in herpangina cases in Japan after the easing of the COVID-19 restrictions during the summer of 2023, along with a noticeable increase in other respiratory illnesses, emphasizing the potential strain on pediatric healthcare and reinforcing the ongoing significance of implementing general infection prevention strategies.

Sitafloxacin- Versus Moxifloxacin-Based Sequential Treatment for Mycoplasma Genitalium Infections: Protocol for a Multicenter, Open-Label Randomized Controlled Trial.

BACKGROUND: Mycoplasma genitalium is an emerging sexually transmitted pathogen associated with increasing antibiotic resistance. The current treatment guidelines recommend moxifloxacin-sequential therapy for macrolide-resistant Mgenitalium or strains with unknown resistance profiles. However, it is unclear whether sitafloxacin, a 4th-generation fluoroquinolone antibiotic, is effective against resistant strains. OBJECTIVE: This study aims to assess and compare the efficacy and safety of sitafloxacin- and moxifloxacin-based treatment regimens for managing Mgenitalium infections. METHODS: We will conduct this randomized controlled trial at multiple centers in Japan. Eligible participants include adults aged 18 years or older with a confirmed Mgenitalium infection, as determined through the nucleic acid amplification test. Patients will be randomly assigned using a stratified approach based on the treatment facility and infection site. The interventions comprise oral sitafloxacin (200 mg) daily for 7 days (with optional pretreatment of oral doxycycline, 200 mg, daily for up to 7 days), with a control group receiving oral doxycycline (200 mg) daily for 7 days followed by moxifloxacin (400 mg) daily for another 7 days. The primary outcome is the treatment success rate with a superiority margin of 10%, as confirmed through the nucleic acid amplification test. Secondary outcomes encompass changes in the bacterial load at the urogenital or rectal sites and the emergence of posttreatment-resistant mutant strains. RESULTS: Enrollment commenced in June 2023 and will conclude in December 2024, with findings anticipated by 2025. The expected success rates fall within the range of 80% for sitafloxacin and 42% for moxifloxacin against Mgenitalium carrying the G248T (S83I) mutation, based on previous studies. Accordingly, with a 5% significance level (2-sided) and 80% statistical power, we aim to recruit 50 participants per group, factoring in a 10% expected dropout rate. CONCLUSIONS: This study will provide valuable insights into the efficacy and safety of sitafloxacin- versus moxifloxacin-based sequential therapy in treating Mgenitalium infections. These findings have the potential to influence clinical guidelines, favoring more effective therapeutic choices. The multicenter approach enhances the robustness of this study. However, a limitation is the potential insufficiency of statistical power to detect posttreatment-resistant mutant strains in each group, rendering posttreatment-resistance mutations a notable concern. In the future, we may need to increase the sample size to enhance power. TRIAL REGISTRATION: Japan Registry of Clinical Trials (jRCTs031230111); https://jrct.niph.go.jp/en-latest-detail/jRCTs031230111. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/52565.

Prevalence of Asymptomatic Mpox among Men Who Have Sex with Men, Japan, January-March 2023.

We prospectively assessed asymptomatic monkeypox virus infections among men who have sex with men in Tokyo, Japan, during the initial phase of the mpox epidemic. Our findings suggest that asymptomatic infections were likely underestimated and were comparable in magnitude to symptomatic infections, highlighting the need to improve testing accessibility among high-risk populations.

Clinical outcomes and epidemiological characteristics of bacteremia in the older Japanese population.

BACKGROUND: The characteristics and clinical consequences of bacteremia in older people, who are highly susceptible to infections, need to be clarified. This study aimed to determine the epidemiological characteristics, prognosis, and predictors of 7-day mortality in patients with community-acquired (CA), healthcare-associated (HCA), and hospital-onset (HO) bacteremia in older adults aged ≥65 years. METHODS: Patients aged ≥65 years with positive blood cultures between April 1, 2015, and March 31, 2018, were divided into three groups: pre-old (65-74 years), old (75-89 years), and super-old (≥90 years). Characteristics based on medical exposure, including CA, HCA, and HO, were also compared and factors related to mortality were identified. RESULTS: Overall, 1716 episodes of bacteremia were identified in 1415 patients. Of the 1211 episodes without contamination, 32.8%, 54.3%, and 12.9% occurred in pre-old, old, and super-old patients. Central line-associated bloodstream infections were more common in pre-old patients and urinary tract infections in the old and super-old. The 7-day mortality rates in the pre-old, old, and super-old groups were 7.4%, 5.8%, and 14.2% (P = 0.002), respectively. Multivariable logistic regression showed that super-old age (adjusted odds ratio, aOR: 2.09 [1.13-3.88], P = 0.019) and HO bacteremia (aOR: 1.97 [1.18-3.28], P = 0.010) were independent risk factors for 7-day mortality. Infectious disease consultation had a protective effect on 7-day mortality (aOR: 0.59 [0.35-0.99], P = 0.047). CONCLUSIONS: The epidemiology of bacteremia differs among older people; thus, they should not be treated as a single entity. A careful approach is needed for the optimal management of bacteremia in these vulnerable patients.

Correction: Conjunctivitis, the key clinical characteristic of adult rubella in Japan during two large outbreaks, 2012-2013 and 2018-2019.

[This corrects the article DOI: 10.1371/journal.pone.0231966.].

Clinical performance testing of the automated haematology analyzer XN-31 prototype using whole blood samples from patients with imported malaria in Japan.

BACKGROUND: The automated haematology analyzer XN-31 prototype (XN-31p) is a new flow cytometry-based device developed to measure the number and the ratio of malaria-infected red blood cells (MI-RBC) with a complete blood count (CBC). The XN-31p can provide results in about one minute and also can simultaneously provide information on the malaria parasite (Plasmodium) species. In this study, clinical testing of the XN-31p was performed using blood samples from patients with imported malaria in Japan. METHODS: Blood samples were collected from 80 patients who visited the hospital of the National Center for Global Health and Medicine, Tokyo, Japan, for malaria diagnosis from January 2017 to January 2019. The test results by the XN-31p were compared with those by other standard methods, such as microscopic observation, rapid diagnostic tests and the nested PCR. RESULTS: Thirty-three patients were diagnosed by the nested PCR as being malaria positive (28 Plasmodium falciparum, 2 Plasmodium vivax, 1 Plasmodium knowlesi, 1 mixed infection of P. falciparum and Plasmodium malariae, and 1 mixed infection of P. falciparum and Plasmodium ovale), and the other 47 were negative. The XN-31p detected 32 patients as "MI-RBC positive", which almost matched the results by the nested PCR and, in fact, completely matched with the microscopic observations. The ratio of RBCs infected with malaria parasites as determined by the XN-31p showed a high correlation coefficient of more than 0.99 with the parasitaemia counted under microscopic observation. The XN-31p can analyse the size and nucleic acid contents of each cell, and the results were visualized on a two-dimensional cytogram termed the "M scattergram". Information on species and developmental stages of the parasites could also be predicted from the patterns visualized in the M scattergrams. The XN-31p showed a positive coincidence rate of 0.848 with the nested PCR in discriminating P. falciparum from the other species. CONCLUSIONS: The XN-31p could rapidly provide instructive information on the ratio of MI-RBC and the infecting Plasmodium species. It was regarded to be of great help for the clinical diagnosis of malaria.

Negative Results of Nucleic Acid Amplification Tests for SARS-CoV-2 in Clinical Practice May Vary among Six Molecular Assays in Patients with COVID-19.

Several commercial nucleic acid amplification tests (NAATs) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed. We used 6 kits available in Japan in 13 NAAT-positive specimens with crossing point values >36 and 7 NAAT-negative specimens from patients with coronavirus disease 2019 (COVID-19), and their results were compared. Specimens positive in ≥2 assays were considered true-positive and examined for concordance with the specimen results. The SARS-CoV-2 Detection Kit -Multi- (Toyobo M; Toyobo, Osaka, Japan) using extracted RNA had the highest concordance (κ = 1.00). This was followed by Cobas® SARS-CoV-2 (Roche, Basel, Switzerland) (κ = 0.79). There was a weak correlation between the number of negative results for each kit and the number of days between onset and testing (Spearman rank correlation: ρ = 0.44; P < 0.05). We believe that the variations in results among kits for specimens with low viral loads should not be problematic when these kits are used for screening infectious patients because these variations are more likely to be observed in specimens tested many days after onset (i.e., those that have lost their infectivity). However, it may be better to use a test for suspected late-stage COVID-19 with a low viral load, such as Toyobo M or Cobas.

Factors associated with high antibody titer following coronavirus disease among 581 convalescent plasma donors: A single-center cross-sectional study in Japan.

INTRODUCTION: The ability to predict which patients with a history of coronavirus disease (COVID-19) will exhibit a high antibody titer is necessary for more efficient screening of potential convalescent plasma donors. We aimed to identify factors associated with a high immunoglobulin G (IgG) titer in Japanese convalescent plasma donors after COVID-19. METHODS: This cross-sectional study included volunteers undergoing screening for convalescent plasma donation after COVID-19. Serum anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) S-protein IgG antibodies were measured using a high-sensitivity chemiluminescence enzyme immunoassay. RESULTS: IgG antibodies were measured in 581 patients, 534 of whom had full information of selected independent variables. Multiple linear regression analysis revealed that increasing age (1.037 [1,025, 1.048]), days from symptom onset to sampling (0.997 [0.995, 0.998]), fever (1.664 [1.226, 2.259]), systemic corticosteroid use during SARS-CoV-2 infection (2.382 [1.576, 3.601]), and blood type AB (1.478 [1.032, 2.117]) predict antibody titer. CONCLUSION: Older participants, those who experienced fever during infection, those treated with systemic corticosteroids during infection, those from whom samples were obtained earlier after symptom onset, and those with blood type AB are the best candidates for convalescent plasma donation. Therefore, these factors should be incorporated into the screening criteria for convalescent plasma donation after SARS-CoV-2 infection.

Fatty liver on computed tomography scan on admission is a risk factor for severe coronavirus disease.

OBJECTIVES: To alleviate the overflow of coronavirus disease 2019 (COVID-19) patients in hospitals, less invasive and simple criteria are required to triage the patients. We evaluated the relationship between COVID-19 severity and fatty liver on plain computed tomography (CT) scan performed on admission. METHODS: In this retrospective cohort study, we considered all COVID-19 patients at a large tertiary care hospital between January 31 and August 31, 2020. COVID-19 severity was categorized into severe (moderate and severe) and non-severe (asymptomatic and mild) groups, based on the Japanese National COVID-19 guidelines. Fatty liver was detected on plain CT scan. Multivariate logistic regression analysis was performed to evaluate factors associated with severe COVID-19. RESULTS: Of 222 patients (median age: 52 years), 3.2%, 58.1%, 20.7%, and 18.0% presented with asymptomatic, mild, moderate, and severe COVID-19, respectively. Although 59.9% had no fatty liver on plain CT, mild, moderate, and severe fatty liver occurred in 13.1%, 18.9%, and 8.1%, respectively. Age and presence of fatty liver were significantly associated with severe COVID-19. CONCLUSION: Our study showed that fatty liver on plain CT scan on admission can become a risk factor for severe COVID-19. This finding may help clinicians to easily triage COVID-19 patients.

Catheter-related bloodstream infection caused by Tsukamurella ocularis: A case report.

Tsukamurella spp. causes mainly bacteremia and central venous catheter-related bloodstream infections. To the best of our knowledge, there is no documented evidence that Tsukamurella ocularis causes catheter-related bloodstream infections like other species of Tsukamurella. We present a novel case of T. ocularis bacteremia in a 69-year-old woman with malignant cancer, wherein the patient was successfully treated with a peripherally inserted central venous catheter. We administered combination antimicrobial therapy to the patient, which was terminated only after confirming the absence of infection. We identified T. ocularis by sequencing three housekeeping genes that could not be identified using conventional mass spectrometry and 16S rRNA gene analysis.

Systemic corticosteroid as an adjunctive treatment for lower respiratory tract infection in children with severe motor and intellectual disabilities.

INTRODUCTION: Children with severe motor and intellectual disabilities (SMID) are susceptible to severe lower respiratory tract infection (LTRI). As SMID patients are prone to develop recurrent wheezing and are often diagnosed with bronchial asthma, they frequently receive systemic corticosteroids as an adjunctive treatment for LRTIs. However, the efficacy of corticosteroid therapy for LTRIs in SMID children is unclear. We investigated whether or not corticosteroid therapy was associated with better clinical outcomes for SMID children with LRTIs. METHODS: Our retrospective study enrolled 217 SMID children 1-15 years old hospitalized for LTRIs. We compared the clinical characteristics and outcomes between patients with and without corticosteroid therapy. RESULTS: Of the 217 patients, 29 (13.3%) received corticosteroid therapy. The proportion of patients with a history of bronchial asthma was higher and LRTI was more severe in patients with corticosteroid therapy than in those without the therapy. The length of hospital stay (LOHS) was significantly longer in patients with corticosteroid therapy (median 13 days) than in those without corticosteroid therapy (median 9 days) (P = 0.02). The same tendency was shown for the LOHS in patients with severe or moderate LRTI, although not to a significant extent. CONCLUSION: Systemic corticosteroid therapy was not associated with better clinical outcomes in SMID children with LRTIs, even if the patients suffer from severe LRTIs. Corticosteroids should be used cautiously for LRTIs in SMID children because bronchial asthma is likely to be overdiagnosed in these children.

Electrocautery ablation therapy for anal intraepithelial carcinoma: A study protocol.

BACKGROUND: Anal cancer is a human papillomavirus-related cancer. Screening with high-resolution anoscopy (HRA) and subsequent therapeutic intervention are increasingly recognized as the standard procedure for anal cancer. Generally, lesions suspected as being high-grade squamous intraepithelial lesions are biopsied and treated if they are grade 2 or 3 anal intraepithelial neoplasia (AIN). According to several studies, electrocautery ablation for grade 2 or 3 AIN is highly effective. However, relapse within and outside the targeted areas after the intervention is a clinical problem. In Japan, electrocautery ablation is not available at most facilities. Therefore, this study aims to investigate the efficacy and safety of electrocautery ablation. METHODS: This single-arm, open-label, pilot intervention study will investigate the efficacy and safety of electrocautery ablative therapy using high-frequency medical devices. Patients diagnosed with grade 2 or 3 AIN will be included and will receive ablation treatment. Then, they will be followed up at 3 and 6 months after the procedure for HRA-guided sextant biopsy. To reduce the possibility of missed lesions before and after the intervention, we will perform HRA-guided sextant biopsy routinely. In this study, a sextant biopsy is defined as at least 6 biopsies in all directions, regardless of abnormal findings under HRA. The primary outcome is the recurrence rate at 6 months, and the secondary outcomes are the adverse event and recurrence rates at 3 months. CONCLUSION: This pilot study will provide data on the effectiveness and safety of electrocautery ablation as a treatment for grade 2 or 3 AIN.

Extracorporeal membrane oxygenation may decrease the plasma concentration of remdesivir in a patient with severe coronavirus disease 2019.

Remdesivir is an antiviral drug that results in clinical improvement after five days of treatment and accelerates recovery by 31%. No studies have discussed the pharmacokinetic analysis of remdesivir in patients with severe COVID-19 requiring extracorporeal membrane oxygenation (ECMO). A 63-year-old American man who underwent mechanical ventilation and ECMO for severe COVID-19 was administered remdesivir for ten days. The loading dosage was 200 mg at 7 PM on day 12 and 100 mg daily at 0:00 PM from day 13-21, administered within 1 h. The pharmacokinetic analysis was performed. The serum creatinine concentration was within the normal range of 0.5-0.7 mg/dL during treatment. According to the pharmacokinetic analysis, the plasma concentrations of remdesivir and GS-441524 4 h after administration (C4) were 662 ng/mL and 58 ng/mL, respectively, and the concentrations 18 h after administration (C18) were 32 ng/mL and 44 ng/mL, respectively. Therefore, the half-life of remdesivir and GS-441524 was 3.2 and 35.1 h, respectively. Monitoring the plasma concentrations of remdesivir and GS-441524 in patients undergoing ECMO may be necessary.

Resurgence of Respiratory Syncytial Virus Infections during COVID-19 Pandemic, Tokyo, Japan.

More than a year into the coronavirus-19 pandemic, intensified infection control measures have controlled most viral respiratory infections in Tokyo, Japan. As of July 2021, however, an unusually high number of respiratory syncytial virus infections were reported in Tokyo. This resurgence may have resulted from restarting social activities for children.

Infection with capsular genotype K1-ST23 hypervirulent Klebsiella pneumoniae isolates in Japan after a stay in East Asia: Two cases and a literature review.

Disseminated community-acquired infections caused by the hypervirulent Klebsiella pneumoniae (hvKp) among relatively healthy individuals in East Asia have been reported in recent years. Isolate of the capsular genotype K1, belonging to sequence type (ST) 23, is the most common causative agent of this disease. We experienced two cases of K1-ST23 infection with a travel history in East Asia, and hvKp infection was diagnosed after entering or returning to Japan. Case 1 was a 45-year-old Myanmar seaman with a history of ischemic heart disease who developed a fever on board and was transported to Japan via Shanghai and Taiwan. He had multiple disseminated lesions due to K. pneumoniae; other symptoms included liver abscess, intraocular inflammation, intraventricular thrombosis, brain abscess, and bloodstream infection. Along with antimicrobial treatment, drainage of liver abscesses and surgery for intraocular inflammation and intraventricular thrombosis were required. The patient was discharged 93 days after admission, with little improvement in the visual acuity. Case 2: A 29-year-old Japanese man with no underlying disease developed a prostate abscess and bloodstream infection caused by K. pneumoniae after a trip to Korea. However, he improved only with antimicrobial treatment. K. pneumoniae in both cases were identified to have the rmpA gene, with capsular genotypes K1 and ST23. Further, both cases were considered to have been infected with hvKp during their stay in East Asia. In conclusion, it is important to suspect disseminated disease and perform a systemic search, taking into account that hvKp may be present in cases of Klebsiella infection acquired from East Asia.

Positive Ratio of Polymerase Chain Reaction (PCR) and Validity of Pre-Screening Criteria at an Outpatient Screening Center during the Early Phase of the COVID-19 Epidemic in Japan.

Despite the increase in COVID-19 cases globally, the number of cases in Japan has been relatively low, and an explosive surge in the prevalence has not occurred. In March 2020, the Ministry of Health, Labour and Welfare (MHLW) in Japan recommended the original criteria for polymerase chain reaction (PCR) testing, although there was a lack of evidence for appropriate targets for COVID-19 testing. This study aimed to evaluate the COVID-19 positive ratio and pre-screening criteria in Tokyo immediately after the insurance-covered SARS-CoV-2 PCR testing became available in Japan. We subjected 277 individuals with mild symptoms in metropolitan Tokyo (positive: 9.0%) from March 9 to 29, 2020, to SARS-CoV-2 PCR testing. The results revealed that 25 (9.0%) of them were PCR-positive. The sensitivity and specificity of the MHLW criteria were 100% and 10.7%, respectively. When the criteria excluded nonspecific symptoms, fatigue, and dyspnea, the sensitivity slightly decreased to 92%, and the specificity increased to 22.2%. The specificity was highest when the fever criterion was ≥37.5°C for ≥4 days, and exposure/travel history, including age and underlying comorbidities, was considered. Our findings suggest that the MHLW criteria, including the symptoms and exposure/travel history, may be useful for COVID-19 pre-screening.