DOCK2 is involved in the host genetics and biology of severe COVID-19.

Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge1-5. Here we conducted a genome-wide association study (GWAS) involving 2,393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3,289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target.

Cardiometabolic health in people with HIV: expert consensus review.

OBJECTIVES: To develop consensus data statements and clinical recommendations to provide guidance for improving cardiometabolic health outcomes in people with HIV based on the knowledge and experience of an international panel of experts. METHODS: A targeted literature review including 281 conference presentations, peer-reviewed articles, and background references on cardiometabolic health in adults with HIV published between January 2016 and April 2022 was conducted and used to develop draft consensus data statements. Using a modified Delphi method, an international panel of 16 experts convened in workshops and completed surveys to refine consensus data statements and generate clinical recommendations. RESULTS: Overall, 10 data statements, five data gaps and 14 clinical recommendations achieved consensus. In the data statements, the panel describes increased risk of cardiometabolic health concerns in people with HIV compared with the general population, known risk factors, and the potential impact of antiretroviral therapy. The panel also identified data gaps to inform future research in people with HIV. Finally, in the clinical recommendations, the panel emphasizes the need for a holistic approach to comprehensive care that includes regular assessment of cardiometabolic health, access to cardiometabolic health services, counselling on potential changes in weight after initiating or switching antiretroviral therapy and encouraging a healthy lifestyle to lower cardiometabolic health risk. CONCLUSIONS: On the basis of available data and expert consensus, an international panel developed clinical recommendations to address the increased risk of cardiometabolic disorders in people with HIV to ensure appropriate cardiometabolic health management for this population.

Effects of the induction of humoral and cellular immunity by third vaccination for SARS-CoV-2.

INTRODUCTION: To control the spread of severe disease caused by mutant strains of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), it is necessary to determine whether continued vaccination enhances humoral and cellular immunity. AIM: In this study, we examined the changes in humoral and cellular immunity to SARS-CoV-2 after administration of the third vaccination in Japanese adults who had received the second dose of messenger ribonucleic acid (mRNA)-1273 vaccine and the third vaccination (BNT162b2 or mRNA-1273). METHODS: We measured anti-spike antibodies in immunoglobulin G (IgG) and anti-nucleocapsid IgG titers in the serum of the vaccinated subjects. To evaluate cellular immunity, the peripheral blood mononuclear cells of inoculated individuals were cultured with spiked proteins, including those of the SARS-CoV-2 conventional strain and Omicron strain, and then subjected to enzyme-linked immunospot (ELISPOT). RESULTS: The results revealed that the anti-SARS-CoV-2 spike protein antibody titer increased after the third vaccination and was maintained; however, a decrease was observed at 6 months after vaccination. SARS-CoV-2 antigen-specific T helper (Th)1 and Th2 cell responses were also induced after the third vaccination and were maintained for 6 months after vaccination. Furthermore, induction of cellular immunity against Omicron strains by the omicron non-compliant vaccines, BNT162b2 or mRNA-1273, was observed. CONCLUSION: These findings demonstrate the effectiveness of vaccination against unknown mutant strains that may occur in the future and provide important insights into vaccination strategies.

Evaluation of a Previously Developed Predictive Model for Infective Endocarditis in 320 Patients Presenting with Fever at 4 Centers in Japan Between January 2018 and December 2020.

BACKGROUND In our previous single-center study, we developed an infective endocarditis (IE) prediction model among patients with undiagnosed fever (UF) based on 5 factors that can be obtained on admission: ambulance transfer, presence of cardiac murmur or pleural effusion, blood neutrophil percentage, and platelet count. The present study aimed to retrospectively evaluate the prediction model for IE in 320 patients presenting with fever at 4 university hospitals in Japan from January 2018 to December 2020. MATERIAL AND METHODS Patients aged ≥20 years admitted to 4 hospitals with I-330 (IE) or R-50-9 (UF) according to the International Statistical Classification of Diseases and Related Health Problems-10 were enrolled. More than 2 physicians at each hospital reviewed the patient diagnoses using the modified Duke criteria, allocating "definite IE" to IE group (n=119) and "non-definite IE" to UF group (n=201). Five factors on admission were analyzed by multivariate logistic regression. The discriminative ability and calibration of the model were evaluated using the area under the curve (AUC) and the shrinkage coefficient, respectively. RESULTS A total of 320 patients were enrolled. The odds ratios (95% confidence intervals) were as follows: ambulance transfer 1.81 (0.91-3.55); cardiac murmur 13.13 (6.69-27.36); pleural effusion 2.34 (0.62-2.42); blood neutrophil percentage 1.09 (1.06-1.14); and platelet count 0.96 (0.93-0.99). The AUC was 0.783 (0.732-0.834) with a shrinkage coefficient of 0.961. CONCLUSIONS The IE prediction model is useful to estimate the probability of IE immediately after admission for fever in patients aged ≥20 years.

Long-term effect of letrozole on metastatic uterine smooth muscle tumors of uncertain malignant potential: A case report.

A 48-year-old woman underwent total abdominal hysterectomy and right salpingo-oophorectomy and was initially diagnosed with a uterine leiomyoma and right ovarian cystadenoma. After 4 years, multiple pulmonary metastases were identified, and treatment with gonadotropin-releasing hormone agonists was started, but stopped later due to disease progression. The patient developed dyspnea and underwent right upper lobectomy. The histopathological findings were consistent with those of pulmonary metastases secondary to a uterine smooth muscle tumor of uncertain malignant potential. Slow disease progression after a poor response to adriamycin and hormone receptor positivity led to the start of letrozole. Letrozole induced spontaneous regression of the pulmonary metastases, and about 2 years into the treatment, sustained response was achieved with minimal side effects. This may be the first case supporting the long-term efficacy and safety of letrozole in the management of adriamycin-resistant lung metastases of uterine smooth muscle tumors of uncertain malignant potential.

Comorbidities and co-medications among 28 089 people living with HIV: A nationwide cohort study from 2009 to 2019 in Japan.

OBJECTIVES: Comorbidities are associated with a high burden of disease in people living with HIV (PLWH). The objective was to investigate the prevalence of chronic comorbidities and use of co-medications in PLWH in Japan. METHODS: This study retrospectively analysed clinical information from PLWH receiving antiretroviral therapy (ART) between April 2009 and March 2019. Demographic characteristics, numbers and types of chronic comorbidities, and numbers and types of non-ART co-medications, were described by age groups. The source of data was the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB). RESULTS: Overall, 28 089 PLWH (male 91.9%) who used ART were identified. Out of 28 089 PLWH, 81.5% had at least one chronic comorbidity. The numbers of AIDS-defining cancers and non-AIDS-defining cancers in this Japanese cohort were 2432 (8.7%) and 2485 (8.8%), respectively. The cumulative burden of comorbidities including non-AIDS-defining cancer increased with age. Changes in trend between 2009 and 2019 were observed, including a higher proportion of PLWH diagnosed at ≥ 70 years old [2019 (4.7%) vs. 2009 (2.4%)] and a decreasing percentage of patients with AIDS-defining cancers (down from 6.3% to 4.8% between 2009 and 2019). The most common co-medications during the most recent 3-month period were lipid-regulating/anti-atheroma preparations (11.3%), antacids, antiflatulents and anti-ulcerants (9.6%), and agents acting on the renin-angiotensin system (8.1%). The three most common therapeutic categories of co-medications during the study period were antacids, antiflatulents and anti-ulcerants (35.0%), systemic antihistamines (33.7%) and psycholeptics (27.1%). More than 30% of PLWH aged > 40 years used at least one co-medication in a 3-month period, while more than half of PLWH aged > 30 years had at least one co-medication prescribed concomitantly for a total of ≥ 90 days during the study period, and the numbers of co-medications used were greater in the older age groups. CONCLUSIONS: The burden of chronic comorbidities and co-medication were found to be greater in older, as compared to younger patients, among 28 089 PLWH in a nationwide study in Japan. This finding suggests the need to identify elderly PLWH and to appropriately manage their HIV and comorbidities.

The universal relationship between sample dimensions and cooperative phenomena: effects of fractal dimension on the electronic properties of high-TC cuprate observed using electron spin resonance.

As demonstrated by the unique electronic properties of nanostructured materials, which are qualitatively different from the bulk properties of the same materials, there should be a general relationship between the dimensions of the sample structures and the physical/chemical properties. However, it is demanding to examine this intriguing problem experimentally, because one cannot prepare a series of samples based on the same material with systematically varying and noninteger dimensions. This problem is solved by considering the fractal dimensions of samples. The electronic structures of a series of powder samples of the high-TC superconductor YBa2Cu3O7-δ with the fractal dimensions (Df) of 2.5-3.0 were investigated using the electron spin resonance (ESR) spectra at 293 K, to determine a general and quantitative relationship between the electronic properties and fractal dimensions of the samples. The observed Df-dependences of ESR parameters, such as g-values and linewidths, were quantitatively consistent with those of the critical temperatures, critical current densities, and lower critical magnetic fields, all of which exhibited anomalies at Df ∼ 2.9. Considering the geometrical features of the fractal models, a hypothesis for explaining the observed Df-dependences of the cooperative phenomena has been proposed, suggesting a universal structural instability at particular fractal dimensions, which affects all the physical and chemical properties of the samples.

Meals and Room Temperature Storage do not Significantly Affect Feasibility of Direct RT-PCR Tests for SARS-CoV-2 Using Saliva.

BACKGROUND: Rapid detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using saliva samples has emerged as a preferred technique since sample collection is easy and noninvasive. In addition, several commercial high-throughput PCR kits that do not require RNA extraction/purification have been developed and are now available for testing saliva samples. However, an optimal protocol for SARS-CoV-2 RT-PCR testing of saliva samples using the RNA extraction/purification-free kits has not yet been established. The aim of this study was to establish optimal preanalytical conditions, including saliva sample collection, storage, and dilution for RNA extraction/purification-free RT-PCR (direct RT-PCR). METHODS: Patients suspected with COVID-19 from March 02 to August 31, 2020, were enrolled in this study. A total of 248 samples, including 43 nasopharyngeal swabs and 205 saliva samples, were collected from 66 patients (37 outpatients and 29 inpatients) and tested using the 2019 Novel Coronavirus Detection Kit (nCoV-DK, Shimadzu Corporation, Kyoto, Japan). RESULTS: The detection results obtained using nasopharyngeal swabs and saliva samples matched 100%. The sampling time, i.e., either awakening time or post-breakfast, had no significant effect on the viral load of the saliva samples. Although saliva samples are routinely diluted to reduce viscosity, we observed that dilution negatively affected PCR sensitivity. Saliva samples could be stored at room temperature (25°C) for 24 hours or at 4°C for up to 48 hours. CONCLUSIONS: This study demonstrated the appropriate conditions of saliva sample collection, processing, and storage, and indicated that the nCoV-DK is applicable to saliva samples, making the diagnosis method simple and safe.

Decreased number of inpatients with community-acquired pneumonia during the COVID-19 pandemic: A large multicenter study in Japan.

The COVID-19 pandemic has shaped the dynamics of many diseases. This study aims to assess how the pandemic affected community-acquired pneumonia admission of all age groups among Japanese hospitals with various size and availability of COVID-19 wards. Our findings revealed a 44%-53% reduction in community-acquired pneumonia admission among 82 hospitals in Japan, from April through September of 2020, compared to the same period of 2019. Decreases were consistently found among hospitals with and without COVID-19 wards. The most significant decrease was found in the age group <20 years old. COVID-19 preventive measures and personal hygiene are considered to be effective measures to prevent the spreading of this disease. As vaccination progresses and the public gradually become less attentive to infection countermeasures, incidence of community-acquired pneumonia may increase in the coming season. Continued monitoring is required.

Real-world medication persistence among HIV-1 patients initiating integrase inhibitor-based antiretroviral therapy in Japan.

INTRODUCTION: Medication persistence has rarely been studied for integrase strand transfer inhibitor (INSTI)-based regimens among patients living HIV (PLWH) in Asia. This study investigated medication persistence for newly prescribed INSTI-based regimens in Japan by comparing single-tablet regimens (STRs) versus multiple-tablet regimens (MTRs), based on the Medical Data Vision database. METHODS: Adult PLWH with ≥2 claims for antiretroviral therapy (ART) of interest between 1 January 2017 and 30 June 2018 were included if they had a ≥3-month continuous enrolment prior to the index date and a ≥6-month follow-up after the index date. Medication persistence was measured as the duration from initiation to discontinuation of the prescribed INSTI-based regimen. RESULTS: Overall, 487 patients were included, with 220 in the STR cohort and 267 in the MTR cohort. Persistence was longer in the STR cohort than in the MTR cohort (mean days on the index regimens: 384.2 vs. 317.3, P < 0.001). MTRs were associated with a higher risk of discontinuation than STRs (hazard ratio [HR], 1.72; 95% confidence interval [CI], 1.18-2.52; P = 0.005). Other factors that were associated with discontinuation were backbone (emtricitabine/tenofovir disoproxil fumarate vs. emtricitabine/tenofovir alafenamide: HR, 5.64; 95% CI, 3.68-8.66; P < 0.001), third agent (raltegravir vs. elvitegravir/cobicistat: HR, 2.06; 95% CI, 1.10-3.86; P = 0.024), age (HR, 1.02; 95% CI, 1.01-1.03; P = 0.007), and the number of non-ART index medications (HR, 1.16; 95% CI, 1.12-1.21; P < 0.001). CONCLUSIONS: Among PLWH newly prescribed an INSTI-based regimen in Japan, STRs were associated with longer persistence than MTRs.

The impact of the COVID-19 pandemic on other infections differs by their route of transmission: A retrospective, observational study in Japan.

INTRODUCTION: The Coronavirus disease 2019 (COVID-19) pandemic and people's subsequent behavioral changes have decreased the cases of respiratory infection worldwide. However, research on infectious diseases with other transmission modes is insufficient. The aim was to assess the impact of the COVID-19 pandemic on non-respiratory infectious diseases: infectious enterocolitis, sexually transmitted diseases such as human immunodeficiency virus (HIV) infection and syphilis, and tick-borne diseases. METHODS: This retrospective, cohort study used comprehensive surveillance data from the National Institute of Infectious Diseases in Japan from January 1, 2018, to December 31, 2021. The number of cases of infectious diseases before the COVID-19 pandemic (2018-2019) was compared with that during the COVID-19 pandemic (2020-2021). Reduction rates were calculated as the number of disease cases during the COVID-19 pandemic in 2020 and 2021, respectively, divided by the mean number of disease cases in 2018 and 2019. RESULTS: The total numbers of cases of infectious enterocolitis, sexually transmitted diseases, and tick-borne diseases during the study period were 2,507,304 cases, 24,972 cases, and 3012 cases, respectively. The number of cases decreased for infectious enterocolitis and sexually transmitted diseases during the COVID-19 pandemic compared with before the COVID-19 pandemic, with an approximately 40-50% decrease in enterocolitis and 30-55% decreases in sexually transmitted diseases. However, cases of tick-borne diseases changed little, with a 0.2% increase in 2020 and a 6% increase in 2021. CONCLUSION: The COVID-19 pandemic had a different impact on the number of cases of infectious diseases depending on their mode of transmission.

Reactogenicity following two doses of the BNT162b2 mRNA COVID-19 vaccine: Real-world evidence from healthcare workers in Japan.

As the first authorized COVID-19 vaccine in Japan, the BNT162b2 mRNA COVID-19 vaccine is utilized for mass vaccination. Although efficacy has been proved, real-world evidence on reactogenicity in Japanese personnel is needed to prepare the public. Healthcare workers in a large academic hospital in Japan received two doses of the Pfizer-BioNTech vaccine from March 17 to May 19, 2021. Online questionnaires were distributed to registered recipients following each dose, from day 0 through day 8. Primary outcomes are the frequency of reactogenicity including local and systemic reactions. Length of absence from work was also analyzed. Most recipients self-reported reactogenicity after the first dose (97.3%; n = 3254; mean age [36.4]) and after the second dose (97.2%; n = 3165; mean age [36.5]). Systemic reactions following the second dose were substantially higher than the first dose, especially for fever (OR, 27.38; 95% CI, [22.00-34.06]; p < 0.001), chills (OR, 16.49; 95% CI, [13.53-20.11]; p < 0.001), joint pain (OR, 8.49; 95% CI, [7.21-9.99]; p < 0.001), fatigue (OR, 7.18; 95% CI, [6.43-8.02]; p < 0.001) and headache (OR, 5.43; 95% CI, [4.80-6.14]; p < 0.001). Reactogenicity was more commonly seen in young, female groups. 19.3% of participants took days off from work after the second dose (2.2% after the first dose), with 4.7% absent for more than two days. Although most participants reported reactogenicity, severe cases were limited. This study provides real-world evidence for the general population and organizations to prepare for BNT162b2 mRNA COVID-19 vaccination in Japan and other countries in the region.

The 24-h reporting of Gram stains from positive blood cultures contributes to physician's use of appropriate antimicrobials: Experience at a university hospital.

Although recent technological advances for the diagnosis of bloodstream infection (BSI) provide rapid and accurate results, blood culture maintains a key role in the diagnosis of BSI. The objective of this study was to determine whether 24-h reporting by telephone to disclose the suspected microorganism based on the Gram stain morphology from positive blood cultures (first laboratory report) affects a physician's use of appropriate antimicrobials. A total of 627 (14%) out of 4413 blood samples, excluding duplicate samples from the same patient on the same day, were positive for blood cultures between January and December 2016. The contamination rate of blood cultures during the study period was 2.3%. Among 627 patients with positive blood cultures, 538 (86%) were receiving antibiotics at the time of the first laboratory report, of which 502 (80%) thereafter continued the same antimicrobials, and the remaining 36 (6%) were changed to appropriate antimicrobials after the first laboratory report. An additional 25 (4%) were newly administered appropriate antimicrobials after the first laboratory report, whereas an additional 21 (3%) were newly administered appropriate antimicrobials after infection control team (ICT)-intervention. The median time lag (interquartile ranges) from flagging culture bottles as positive to a physician's use of appropriate antimicrobials after the first laboratory report (4 h, 2-7) was significantly (p < 0.001) shorter than that after ICT-intervention (12 h, 10-17). During the study period, no cases of discrepancy between the Gram stain morphology in the first laboratory report and definitive identification of microorganisms in the final laboratory report were observed. Because the timing of flagging culture bottles as positive tends to fall outside normal working hours, immediate 24-h reporting by telephone to disclose the suspected microorganism based on the Gram stain morphology from positive blood cultures may contribute to an early recognition of bacteremia and the physician's use of appropriate antimicrobials.

Delayed diagnosis of human immunodeficiency virus infection in people diagnosed with syphilis: A nationwide cohort study from 2011 to 2018 in Japan.

Early treatment of HIV infection depends on timely diagnosis, but many persons living with HIV/AIDS (PLWHA) are unaware of their infection. Though many patients seeking medical attention for sexually transmitted diseases have HIV, many patients' HIV co-infection is undiagnosed in Japan. This is the first report to analyze the timing of syphilis infection in PLWHA of all ages through the use of the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB), containing clinical data of the largest group of HIV-positive patients available in Japan. Overall, 1521 PLWHA (male 93.2%) newly diagnosed and started on antiretroviral therapy were identified in 2016, and 646 (42.5%) patients had a diagnosis of syphilis between 2011 and 2018. Although 100 patients were diagnosed with syphilis before their HIV diagnosis, only 17 (17.0%) had been tested for HIV. Over 50 patients per year became infected with syphilis even after their HIV diagnosis (2017, n = 65 (4.3%); 2018, n = 58 (3.8%)). Although early diagnosis of HIV infection is important, most syphilis patients in Japan had not been properly tested for HIV infection. Since a certain number of HIV patients developed syphilis after HIV diagnosis, education for newly diagnosed HIV patients is important.

Syphilis in people living with HIV does not account for the syphilis resurgence in Japan.

OBJECTIVES: This study aimed to determine whether the current syphilis resurgence in Japan is attributable to incident syphilis in people living with HIV (PLWH). METHODS: This observational, retrospective, population-based study used data from the Japanese National Database. Data were extracted for PLWH who received antiretroviral treatment between January 2009 and December 2018. Using these data, along with the annual number of PLWH and syphilis diagnoses in the total population of Japan acquired from the National Institute of Infectious Diseases, the fraction of PLWH with syphilis compared to the total number of syphilis patients reported each year was calculated. RESULTS: There was a dramatic increase in syphilis cases during the study period. However, the incidence of syphilis in PLWH was stable during 2010-2018; the fraction of PLWH with newly diagnosed syphilis remaining at approximately 2% of the total PLWH cases in Japan each year. The proportion of newly diagnosed syphilis cases in PLWH decreased during the study period and accounted for <10% of the total syphilis cases in Japan since 2016 (14.9% in 2015 to 9.5% in 2016 and 5.9% in 2018). An increasing trend in the number of newly diagnosed syphilis cases in PLWH aged >50 years was observed (7.4% in 2010 to 10.4% in 2014 and 14.9% in 2018). CONCLUSIONS: The recent dramatic increase in syphilis cases in Japan was not seen in PLWH. Thus, the resurgence of syphilis in Japan cannot be attributed to its transmission in the PLWH population.

COVID-19-induced acute renal tubular injury associated with elevation of serum inflammatory cytokine.

BACKGROUND: Severe acute respiratory syndrome Coronavirus 2 has rapidly spread worldwide, with acute kidney injury (AKI) as one of the manifestations with unknown causal mechanisms. We aimed to investigate tubular injury by assessing tubular markers and their association with the severity of Coronavirus disease 2019 (COVID-19). METHODS: We examined the associations between laboratory markers and urinary levels of N-acetyl-ß-D-glucosaminidase (uNAG), ß2-microglobulin (u ß2MG), α1-microglobulin (u α1MG), and liver-type fatty acid binding protein (L-FABP). We studied 18 COVID-19 patients without previous chronic kidney disease and analyzed the relationship between the urinary biomarkers and inflammatory markers in patients with severe (n = 7) or non-severe (n = 11) COVID-19, defined by requirements of supplemental oxygen. RESULTS: Fourteen patients (78%) showed abnormal urinalysis findings and two (11%) developed AKI. Patients with severe COVID-19 had significantly higher levels of proteinuria, uNAG, uß2MG, uα 1MG, and L-FABP than those with non-severe disease. Serum levels of interleukin-6 (IL-6) were significantly higher on admission in all severe COVID-19 cases and correlated with the levels of L-FABP, uß2MG, uα1MG, uNAG, and proteinuria. Moreover, the changes in serum IL-6 (ΔIL-6) levels from baseline to 7 days after admission significantly correlated with ΔL-FABP and Δuß2MG. CONCLUSIONS: Levels of tubular injury markers, especially L-FABP and uß2MG, were significantly associated with IL-6 levels even in patients with no evident AKI. This suggests that L-FABP and uß2MG could be useful as early detective biomarkers for COVID-19 associated renal injury.

A preliminary analysis of the performance of a targeted HIV electronic medical records alert system: A single hospital experience.

Early treatment of HIV relies on a timely detection of the infection, but many people living with HIV/AIDS are unaware of their infection. In the current study, we applied an electronic medical records (EMR)-based alert system flagging high-risk patients previously diagnosed with infections of syphilis, hepatitis A virus, hepatitis B virus, and/or hepatitis C virus, and those aged 20-50 years with a prior diagnosis of shingles. During the study period (April to October 2019), a total of 47 individuals among 22,264 patients visiting our department were identified as having high-risk of carrying HIV, and 14 of these individuals underwent HIV testing. Two males aged below 65 years with a previous diagnosis of syphilis were subsequently tested positive for HIV. This preliminary analysis of the EMR alert system facilitated the identification of high-risk people possibly carrying HIV, but the test rate remains to be improved.

Investigation of the Physiological, Biochemical and Antifungal Susceptibility Properties of Candida auris.

BACKGROUND: Candida auris is an emerging pathogen associated with outbreaks in clinical settings. Isolates of the pathogen have been geographically clustered into four clades with high intra-clade clonality. Pathogenicity varies among the clades, highlighting the importance of understanding these differences. OBJECTIVES: To examine the physiological and biochemical properties of each clade of C. auris to improve our understanding of the fungus. METHODS: Optimal growth temperatures of four strains from three clades, East Asia, South Asia and South Africa, were explored. Moreover, assimilation and antifungal susceptibility properties of 22 C. auris strains from the three clades were studied. RESULTS: The optimal growth temperatures of all strains were 35-37 °C. Assimilation testing demonstrated that the commercial API ID 32 C system can be used to reliably identify C. auris based on the biochemical properties of the yeast. Notably, C. auris can be uniquely differentiated from commonly clinical fungi by its ability to assimilate raffinose and inability to utilize D-xylose, suggesting a useful simple screening tool. The antifungal susceptibility results revealed that all strains are resistant against fluconazole (minimal inhibitory concentration (MIC) 4 to > 64 µg/mL) and miconazole (MIC 8 to > 16 µg/mL), with strains from the Japanese lineage showing relatively lower MIC values (1-4 µg/mL). Conversely, itraconazole, voriconazole, amphotericin B, micafungin and caspofungin were active against most of the tested strains. On the clade level, East Asian strains generally showed lower MICs against azoles comparing to the other clades, while they displayed MICs against flucytosine higher than those of strains from South Africa and South Asia clades. CONCLUSION: Our data suggest a simple identification approach of C. auris based on its physiological and biochemical properties and highlight aspects of C. auris population from various clades.

CD8+ T-cell encephalitis mimicking PRES in AIDS: a case report.

BACKGROUND: Diverse mechanisms including infections, autoimmune inflammatory reactions, neoplasms, and degeneration are involved in the central nervous system in cases of acquired immune deficiency syndrome. In such cases, it is difficult to determine the precise pathogenesis by radiological examination and laboratory testing. CASE PRESENTATION: We report a 37-year-old Japanese woman who had untreated hypertension and gender identity disorder and had been taking testosterone injections since she was 19 years old. She developed a headache and visual field deficits together with elevated blood pressure. According to radiological findings, she was initially suspected as having posterior reversible encephalopathy syndrome in the right parieto-occipital lobe with reversible cerebral vasoconstriction syndrome. Human immunodeficiency virus antibody was positive and the CD4+ T-lymphocyte count was 140 cells/µl. Therefore, antiretroviral therapy was started. Antiretroviral therapy suppressed the activity of acquired immune deficiency syndrome but worsened her visual symptoms and expanding radiological lesions. Brain biopsy led to the diagnosis of CD8+ encephalitis, and she also fulfilled the diagnosis of paradoxical immune reconstitution inflammatory syndrome. Corticosteroid therapy alleviated her symptoms. CONCLUSIONS: This is a rare case of CD8+ encephalitis, with an exacerbation owing to paradoxical immune reconstitution inflammatory syndrome after antiretroviral therapy, which radiologically mimicked posterior reversible encephalopathy syndrome. Corticosteroid therapy was effective; thus, it is important to provide a pathological diagnosis in such cases.

Trajectories of kidney function and associated factors among community-dwelling older Japanese: a 16-year longitudinal study.

BACKGROUND: No study has reported trajectories of kidney function in later life. This long-term prospective study attempted to classify trajectories of estimated glomerular filtration rate (eGFR) and identify factors associated with these trajectories. METHODS: We collected data from annual geriatric health checkups conducted during 2002-2017 in Kusatsu Town, Gunma Prefecture, Japan. The participants were 1990 adults aged 65-90 years (mean [SD] age, 71.0 [5.7] years; 57.0% women), and the total number of observations was 9291. Data were analyzed with a group-based semiparametric mixture model and age-adjusted univariable cumulative logit models. RESULTS: Trajectory of kidney function, as determined by eGFR, was classified as low, middle, and high (4.8%, 38.9%, and 56.3% of men, respectively, and 5.2%, 31.5%, and 63.3% of women). Among men and women in the low trajectory group, chronic kidney disease (CKD) stage worsened from stage G3a (51.8 ml/min/1.73 m2 in men and 53.6 in women) at age 65 years to stage G4 (28.0 ml/min/1.73 m2 in men and 28.5 in women) by age 85 years. A history of hypertension (men and women) and heart disease (men) were more likely in the low trajectory group than in the middle and high trajectory groups. CONCLUSIONS: About 5% of community-dwelling older adults had an eGFR < 30 later in life. Our findings suggest that those with stage G3a CKD at age 65 years should be managed intensively, to control risk factors for CKD progression.