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In patients infected with human immunodeficiency virus (HIV)-1 at our hospital, we observed increases in skin and soft-tissue infections (SSTIs) by community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA). Therefore, we analyzed factors related to CA-MRSA infection and performed a molecular epidemiological investigation.HIV-1-infected patients were diagnosed with SSTIs related to S. aureus between 2007 and 2017, and MRSA was classified into community and hospital-acquired types according to published criteria. Information was collected retrospectively from clinical records, and multivariate analysis by logistic regression was performed concerning factors related to CA-MRSA infection. We evaluated the staphylococcal cassette chromosome mec (SCCmec) type, multilocus sequence type, and the presence of genes encoding Panton-Valentine leucocidin (PVL) in 27 MRSA samples isolated during and after 2015.We found 218 episodes of SSTIs in 169 patients, and among initial episodes of SSTIs, the MRSA ratio was higher from 2015 to 2017 relative to that from 2007 to 2014 (88% vs. 44%; p 0.0001). Multivariate analysis showed that in men having sex with men [MSM; odds ratio (OR): 13] and exhibiting onset during and after 2015 (OR: 5.4), CD4These data describe an increased prevalence of SSTIs due to PVL-positive ST8-MRSA-IV, not previously considered epidemic in Japan, in MSM infected with HIV-1 in Osaka, Japan.

A new design concept for polymer electrolyte fuel cells, which included a flat-metal separator and a gas diffusion layer (GDL) with interdigitated gas flow channels (FCs), was developed in our previous research. This design led to improved performance compared to that obtained with the conventional design of a metal separator with FCs and a flat GDL. Applications of the interdigitated gas flow channels formed on the separator, however, have conventionally faced two issues associated with low performance: one occurs under high humidity conditions because of nonuniform gas flow due to accumulated water in the GDL; the other is caused by forced water discharge from the GDL under low humidity conditions. In this study, both conventional and new cell designs are tested with single cells of 1 cm2 active area, and the performances are compared at high and low humidity with various conditions of gas supply. From these results, we have found that the new design of the GDL with interdigitated channels has a clear advantage over the conventional interdigitated cell in being able to maintain high performance under conditions of both water excess and water shortage.

Background Circulating interferon-γ (IFN-γ) concentration may be sustained at a high level regardless of the initiation of antiretroviral therapy (ART) in some patients with HIV-1 infection. In the present study, we examined the clinical characteristics of HIV-1-infected patients with high levels of plasma IFN-γ. Methods The study subjects were patients infected with HIV-1 who were either naïve to ART with CD4+ cell count > 200 cells/μL (n = 12), or had achieved viral suppression after ART for over a year (n = 188). The levels of plasma IFN-γ and interleukin-6 (IL-6) were measured by the enzyme-linked immunosorbent assay. Patients were divided into high IFN-γ and low IFN-γ groups based on a cutoff level of 5 pg/mL. Results The high IFN-γ group included 41 patients (21%). Compared to the patients on ART with low IFN-γ levels, those on ART in the high IFN-γ group were more likely to be younger than 50 years of age (P = 0.0051) and less likely to have dyslipidemia (P = 0.0476) or to be on a protease inhibitor (P = 0.0449). There was no significant difference between groups in the median increase of CD4+ cell counts from the initiation of ART for up to 3 years. However, after 4 years, the increase in CD4+ cell counts was significantly lower in the high IFN-γ group compared with that in the low IFN-γ group. There were no such significant differences between patients with low and high (> 2 pg/mL) levels of plasma IL-6. Conclusion We concluded that HIV-1-infected patients with high levels of circulating IFN-γ did not have a higher rate of comorbidities related to immune activation. However, they exhibited lower CD4+ cell count recovery after 4 years of being on ART. This deficit could be a consequence of persistent immune activation. Electronic supplementary material The online version of this article (10.1186/s12879-018-3643-2) contains supplementary material, which is available to authorized users.

Infections caused by carbapenemase-producing Enterobacteriaceae (CPE) are becoming increasingly common worldwide. Although CPE infections can be fatal, few reports in the literature have described effective and successful treatments for infectious diseases caused by several types of IMP CPE, and, to our knowledge, no reports have described the successful treatment of IMP-6 CPE infections. We describe two patients who developed bacteremia caused by IMP-6 CPE after surgery for cancer who were successfully treated with amikacin plus high-dose prolonged-infusion meropenem. Both patients were treated over a 2-week period using amikacin 15 mg/kg at various intervals based on therapeutic drug monitoring and meropenem 2000 mg infused over 3 hours every 12 hours. The dosages of amikacin and meropenem were determined based on the creatinine clearance of each patient. Both patients were cured of their bacteremia and did not experience any antibiotic-related adverse effects. Based on the outcomes of these patients, it appears that amikacin plus high-dose prolonged-infusion meropenem may be safe and effective for the treatment of bacteremia caused by IMP-6 CPE.

INTRODUCTION HIV infection is known to cause a variety of central nervous system complications, such as malignant lymphoma (ML), toxoplasma encephalopathy, cryptococcal encephalopathy, progressive multifocal leukoencephalopathy (PML), brain tuberculosis and HIV encephalopathy. In our hospital, we performed brain biopsy for HIV-positive patients with central nervous system lesions suspected malignant lymphoma, or cases difficult to diagnose with blood, cerebrospinal fluid, and imaging alone. In this study, we retrospectively examined HIV-positive patients who underwent brain biopsy at our hospital, and analyzed diagnosis and treatment of patients with ML. Methods HIV-positive patients who underwent brain biopsy in our hospital from January 2010 to April 2019 were examined in this study. We analyzed background factors, preoperative examination results, pathological diagnosis, treatment and prognosis. RESULTS There were 1,894 HIV-positive patients who were treated at our hospital during the period, of which 16 cases underwent a total of 18 brain biopsies. The final diagnosis was 7 ML (6 PCNSL, 1 brain metastasis), 3 toxoplasma encephalopathy, 1 PML, 1 brain tuberculosis, 1 immune reconstitution syndrome, 1 Penicillium marneffei infection, 1 hematoma and one case that could not be diagnosed. In patients with ML, preoperative sIL-2 receptor was higher and EBV positive cases in cerebrospinal fluid tended to be more common (p=0.051, p=0.086, respectively). Five of the six patients with PCNSL were treated at our hospital, four of which were treated with highly active antiretroviral treatment (HAART) and whole-brain irradiation and one with HAARA alone, resulting four with CR and one with SD. Four patients, except one who had sudden death of unknown cause, were still alive without recurrence (median observation period 44.5 months). CONCLUSION At the moment, it is difficult to diagnose ML without brain biopsy. HIV-positive status has been regarded as a poor prognosis factor in PCNSL patients, but the prognosis seems to have improved with HAART.

Raltegravir (RAL), an HIV integrase inhibitor, is metabolized mainly by UDP-glucuronosyltransferase 1A1 (UGT1A1). Polymorphisms in UGT1A1 may cause alterations in the pharmacodynamics of RAL, which is taken twice daily with no dietary restrictions. We compared the effect of two polymorphic alleles in this gene, UGT1A1*6 and UGT1A1*28 on plasma RAL concentrations in Japanese HIV-1-infected patients. Of 114 Japanese HIV-1-infected patients who received RAL, the frequencies of UGT1A1*6 and UGT1A1*28 were 18% and 13%, respectively. The percentage of homozygotes for UGT1A1*6 and UGT1A1*28 was 6% and 4%, respectively, the percentage of compound heterozygotes for UGT1A1*6 and UGT1A1*28 was 2%, and that of heterozygotes for UGT1A1*6 and UGT1A1*28 was 22% and 17%, respectively. RAL plasma trough concentrations were compared for each polymorphism. Significantly higher levels of RAL were observed with patients who were homozygous for UGT1A1*6 (median: 1.0 μg/mL) than for the normal allele (median: 0.11 μg/mL; p = 0.021). Multivariate logistic regression analysis showed that the presence of one or two alleles of UGT1A1*6 or two alleles of UGT1A1*28 were independent factors associated with high RAL plasma trough concentrations (≥ 0.17 μg/mL). These results indicated that UGT1A1*6 and UGT1A1*28 are both factors influencing the RAL plasma trough concentrations in Japanese HIV-1-infected patients.

Background Dolutegravir (DTG) is metabolized mainly by uridine diphosphate (UDP)-glucuronosyltransferase 1A1 (UGT1A1), and partly by cytochrome P450 3A (CYP3A). Therefore, we focused on UGT1A1 gene polymorphisms (*6 and *28) in Japanese individuals infected with human immunodeficiency virus (HIV)-1 to examine the relationship between their plasma trough concentration of DTG and gene polymorphisms. Recently, neuropsychiatric adverse events (NP-AEs) after the use of DTG have become a concern, so the association between UGT1A1 gene polymorphisms and selected NP-AEs was also investigated. Methods The study subjects were 107 Japanese patients with HIV-1 infections who were receiving DTG. Five symptoms (dizziness, headache, insomnia, restlessness, and anxiety) were selected as NP-AEs. The subjects were classified by their UGT1A1 gene polymorphisms for the group comparison of DTG trough concentration and the presence or absence of NP-AEs. Results The subjects consisted of eight (7%) *6 homozygotes, three (3%) *28 homozygotes, four (4%) for *6/*28 compound heterozygotes, 23 (21%) *6 heterozygotes, 18 (17%) *28 heterozygotes, and 51 (48%) patients carrying the normal allele. The plasma DTG trough concentration of the *6 homozygous patients was significantly higher than that of the patients carrying the normal allele (median, 1.43 and 0.82 μg/mL, respectively, p = 0.0054). The *6 and *28 heterozygous patients also showed significantly higher values than those shown by patients with the normal allele. Multivariate analysis revealed that carrying one or two UGT1A1*6 gene polymorphisms, one UGT1A1*28 polymorphism, and age of

The development of herpes zoster is associated with reduced varicella zoster virus (VZV)-specific cell-mediated immune (CMI) reactions. In this study, VZV-specific CMI reactions in 42 anti-VZV-IgG antibody-positive adults infected with HIV-1 were evaluated by measuring the IFN-γ production levels in whole blood in response to stimulation with ultraviolet light-inactivated live attenuated VZV vaccine. The median VZV-specific IFN-γ production level in all patients was 63 pg/ml. Antiretroviral therapy (ART)-naive patients with an AIDS-defining illness (HIV classification category C) had significantly lower IFN-γ production than ART-naive patients in categories A and B and patients receiving ART (P=0.0194 and P=0.0046, respectively). IFN-γ production increased significantly in patients within 1 month of the onset of recurrent VZV disease and at more than 1 year from onset, compared with patients who had never had recurrent VZV disease (P=0.0396 and P=0.0484, respectively). In multivariate analyses, category C and history of recurrent VZV disease were significant factors affecting IFN-γ production. Levels of IFN-γ were measured before and after ART in seven ART-naive patients with no history of recurrent VZV disease, and no significant changes were observed. The results indicate that VZV-specific CMI reactions were reduced in patients with an AIDS-defining illness and enhanced in patients with a history of recurrent VZV disease, but not enhanced by ART alone. Vaccination may be necessary to inhibit the development of herpes zoster in patients receiving ART; this IFN-γ releasing assay is one useful method for evaluating VZV-specific CMI reactions in clinical settings.

High human herpesvirus 8 (HHV-8) seroprevalence has been reported in men who have sex with men (MSM) and are infected with HIV-1. However, it is unclear when they become infected with HHV-8. Thus, we conducted cross-sectional and longitudinal investigations of HHV-8 seroprevalence in HIV-1-infected individuals in Osaka, Japan.Plasma was collected from 121 individuals infected with HIV-1 and the anti-HHV-8 antibody titer was measured using an enzyme-linked immunosorbent assay with whole virus lysate. Subjects were classified into those with and without a past medical history of HHV-8-associated disease; the latter group was then classified into 3 subgroups based on the assumed route of HIV-1 infection: blood products, homosexual contact, and other routes. HHV-8 seroprevalence was compared among the groups and measured again approximately 3 years after the baseline measurement. The relationship between HHV-8 seropositivity and possible associated factors was also investigated.All 15 subjects with HHV-8-associated disease were seropositive, and all 11 subjects in the blood product group were seronegative. In the MSM group, 25 (30%) of 79 subjects were HHV-8 seropositive and, in the non-MSM group, 1 (6%) of 16 subjects was (p 0.0001). In the longitudinal investigation, seroconversion was observed in 10 (19%) of 52 subjects in the MSM group who were seronegative at baseline. A correlation was observed between seroconversion and symptomatic syphilis (p = 0.0432).HHV-8 seropositivity and seroconversion rates were high in HIV-1-infected MSM, suggesting that, currently, HHV-8 is an epidemic pathogen in this population.

A 44-year-old male, who was HIV seropositive, developped weight loss, high grade fever, and multiple lymphadenopathies. Bone marrow biopsy revealed a granuloma lesion, and at the same part of the specimen, Ziehl Neelsen staining showed multiple mycobacterium diffusely arranged in the histocytes. The culture did not show positive after 6 to 8 weeks. Finally we diagnosed disseminated Mycobacterium genavense using a house-keeping gene analysis including 16S rRNA sequencing of lymph punctate with fine needle aspiration and the specimen from the biopsy of the lymph node. If a specimen tests positive for Ziehl Neelsen staining smear positive, culture negative, and PCR negative for tuberculosis and Mycobacterium avium complex, we should consider M. genavense infection as one of the differential diagnoses.

Background Estimates of the interval from HIV-1 infection to disease progression may be affected by selection bias, and data concerning asymptomatic early seroconverters are limited. We examined the interval until disease progression in HIV-1 seroconverters in whom the timing of infection could be estimated within 1 year before diagnosis. Methods Subjects included newly diagnosed patients at Osaka National Hospital between 2003 and 2010 who had either (1) symptomatic acute HIV-1 infection with a negative or intermediate reaction on Western blotting and a positive reaction on an HIV RNA test (symptomatic acute group) or (2) a positive reaction on Western blotting at diagnosis and a

A 46-year-old man presented with a high-grade fever, multiple lymphadenopathies, hepatosplenomegaly and human immunodeficiency virus (HIV) seropositivity, without severe immunosuppression. We suspected human herpesvirus-8 (HHV-8)-associated multicentric Castleman's disease (MCD) based on the results of a physical examination and laboratory investigations, including bone marrow aspiration. However, the patient died eight days after admission due to multiorgan failure. An autopsy revealed MCD and lymphoma cell infiltration in multiple organs. The final diagnosis was large B-cell lymphoma (LBCL) arising in HHV-8-associated MCD. This case illustrates the potential for LBCL in HHV-8 MCD in HIV-infected patients with hepatosplenomegaly and lymphadenopathy without severe immunosuppression and highlights the clinical significance of bone marrow aspiration.

The development of herpes zoster is associated with reduced varicella zoster virus (VZV)-specific cell-mediated immune (CMI) reactions. In this study, VZV-specific CMI reactions in 42 anti-VZV-IgG antibody-positive adults infected with HIV-1 were evaluated by measuring the IFN-γ production levels in whole blood in response to stimulation with ultraviolet light-inactivated live attenuated VZV vaccine. The median VZV-specific IFN-γ production level in all patients was 63 pg/ml. Antiretroviral therapy (ART)-naïve patients with an AIDS-defining illness (HIV classification category C) had significantly lower IFN-γ production than ART-naïve patients in categories A and B and patients receiving ART (P=0.0194 and P=0.0046, respectively). IFN-γ production increased significantly in patients within 1 month of the onset of recurrent VZV disease and at more than 1 year from onset, compared with patients who had never had recurrent VZV disease (P=0.0396 and P=0.0484, respectively). In multivariate analyses, category C and history of recurrent VZV disease were significant factors affecting IFN-γ production. Levels of IFN-γ were measured before and after ART in seven ART-naïve patients with no history of recurrent VZV disease, and no significant changes were observed. The results indicate that VZV-specific CMI reactions were reduced in patients with an AIDS-defining illness and enhanced in patients with a history of recurrent VZV disease, but not enhanced by ART alone. Vaccination may be necessary to inhibit the development of herpes zoster in patients receiving ART; this IFN-γ releasing assay is one useful method for evaluating VZV-specific CMI reactions in clinical settings.

Recently, 2 monoclonal antibodies that specifically inhibit mitochondrial creatine kinase (MtCK) activity have been developed. In this study, we measured the serum MtCK activity in HIV-1-infected individuals (n = 100) by employing a novel method using these antibodies. The mean serum MtCK activity in 44 patients treated with highly active antiretroviral therapy (HAART) including tenofovir disoproxil fumarate (TDF) was 16.0 IU/L. The MtCK activity was significantly higher in patients receiving TDF than in those receiving HAART without TDF (3.4 IU/L) or in naive patients (6.9 IU/L) (Tukey–Kramer test, p < 0.0001 and p = 0.0029, respectively). The serum MtCK activity reached a plateau at 1 month after the initiation of TDF administration and decreased upon discontinuation. It showed no significant correlation with the trough plasma TDF concentration, serum creatinine level, or red blood cell count. The activity was elevated in 75% of the patients receiving TDF, and this elevation was specific to TDF; it was not observed with other anti-HIV drugs. In addition, our report emphasizes the careful interpretation of creatine kinase-MB (CK-MB) test results in patients receiving TDF because MtCK in serum could cause false-positive results on a conventional CK-MB test, which does not include MtCK-specific inhibitory antibodies.

To investigate the thermal behavior during fast hydrogen filling process, the simple one-dimensional analysis considering the heat conduction in tank wall and the three-dimensional numerical simulation dealing with inner gas region were carried out. The numerical analyses were subject to the fast filling test of 35 MPa hydrogen gas into 34 litter tank for 80 seconds. The one-dimensional analysis predicted the temperature rise and the heat loss into surrounding air qualitatively and the averaged temperature of tank wall was underestimated. On the other hand, the three-dimensional simulation overestimated the temperature distribution because of using adiabatic wall condition. However, the effects of buoyant force and convective flow on local thermal profile were fully explained from our numerical results.

A 44-year-old male, who was HIV seropositive, developped weight loss, high grade fever, and multiple lymphadenopathies. Bone marrow biopsy revealed a granuloma lesion, and at the same part of the specimen, Ziehl Neelsen staining showed multiple mycobacterium diffusely arranged in the histocytes. The culture did not show positive after 6 to 8 weeks. Finally we diagnosed disseminated Mycobacterium genavense using a house-keeping gene analysis including 16S rRNA sequencing of lymph punctate with fine needle aspiration and the specimen from the biopsy of the lymph node. If a specimen tests positive for Ziehl Neelsen staining smear positive, culture negative, and PCR negative for tuberculosis and Mycobacterium avium complex, we should consider M. genavense infection as one of the differential diagnoses.