Yusuke Yoshino

Cryptococcus gattii Genotype VGIIa Infection in Man, Japan, 2007

We report a patient in Japan infected with Cryptococcus gattii genotype VGIIa who had no recent history of travel to disease-endemic areas. This strain was identical to the Vancouver Island outbreak strain R265. Our results suggest that this virulent strain has spread to regions outside North America.

Clinical efficacy of peramivir in adult patients with seasonal influenza during the winter of 2012 in Japan

Peramivir is an intravenously administered neuraminidase inhibitor for influenza. The clinical efficacy of peramivir remains unclear because it is used in a limited number of countries. We compared the clinical efficacy of peramivir with that of oseltamivir in influenza patients during the 2012–2013 season.

Characteristics of Serum Endocan Levels in Infection

Objectives Endocan is a newly recognized biomarker of sepsis. However, there have been no studies of the trends in endocan levels during infection and their associations with other clinical factors. The aim of this study was to assess the time course of endocan levels and the associations of endocan with clinical factors during infection by comparison with other biomarkers. Methods Serum samples and blood cultures were obtained from patients who were diagnosed with infection from June 2013 to March 2014. Serum endocan, C-reactive protein (CRP), and procalcitonin (PCT) levels during four periods during infection were measured (day 0, day 1-2, day 3-5, and day 6-10). Results A total of 78 patients were enrolled in this study. The median endocan level decreased by only 23% during infection, whereas both serum CRP and PCT levels decreased by more than 80%. Endocan levels were correlated to neither CRP levels nor PCT levels in each period. Endocan levels at day 0 in patients with bacteremia were higher than those without bacteremia (1.09 ng/mL vs 0.82 ng/mL, P=0.002), but neither CRP levels nor PCT levels at day 0 were different between the two groups. Areas under the receiver operator characteristic (ROC) curves of endocan, CRP, and PCT at day 0 were 0.662, 0.343, and 0.563, respectively. Positive blood cultures tended to be related to high endocan levels, but not significantly (odds ratio: 4.24, 95% CI: 0.99-10.34, P=0.05). Conclusions In bacteremic cases, serum endocan levels in bacteremia tended to be higher than in non-bacteremic cases. Although endocan level was not identified as a prognostic factor of bacteremia, further prospective study concerning the relationship between serum endocan level and bacteremia would be needed.

Lopinavir inhibits insulin signaling by promoting protein tyrosine phosphatase 1B expression

Treatment with antiretroviral therapy, including protease inhibitors (PIs), may result in metabolic side-effects, for example insulin resistance. The aim of the present study was to investigate the mechanism of the dysregulation of insulin signaling by two PIs, lopinavir and darunavir, by analyzing changes in the expression or activity of proteins associated with insulin signaling. 3T3-L1 preadipocytes were pretreated with lopinavir or darunavir for 48 h and then stimulated with insulin for 30 min. The cell lysates were subjected to western blotting with anti-phospho-insulin receptor substrate (IRS) 1, anti-IRS1, anti-suppressor of cytokine signaling (SOCS) 1, anti-SOCS3 and anti-protein tyrosine phosphatase (PTP) 1B antibodies and to immunoprecipitation with anti-IRS1 antibody. Translocation of glucose transporter 4 (GLUT4) following treatment with lopinavir or darunavir was observed using immunofluorescence. While GLUT4 was recruited to the cellular membrane in control adipocytes following insulin stimulation, it was diffusely distributed in the cytosol in lopinavir-treated adipocytes. In darunavir-treated adipocytes, GLUT4 was mainly recruited to the cellular membrane, but some GLUT4 remained in the cytosol. After insulin stimulation, IRS1 was tyrosine-phosphorylated to a greater extent in control adipocytes compared with darunavir-treated adipocytes. Tyrosine phosphorylation of IRS1 was inhibited in lopinavir-treated adipocytes. The expression of PTP1B was upregulated in adipocytes pretreated with the PIs, particularly lopinavir, compared with those pretreated with a vehicle control. The degree of regulation in insulin signaling differs between lopinavir and darunavir. One mechanism by which lopinavir regulates insulin signaling is by the promotion of PTP1B expression.

Infective endocarditis due to Enterobacter cloacae resistant to third- and fourth-generation cephalosporins

We report the case of using a long-term combination of meropenem and amikacin to treat infective endocarditis caused by Enterobacter cloacae resistant to third- and fourth-generation cephalosporins. Multi-drug resistant Gram-negative bacilli, such as the E. cloacae in our study, may become possible pathogens of infective endocarditis. Our experience with this case indicates that long-term use of a combination of β-lactam and aminoglycosides might represent a suitable management option for future infective endocarditis cases due to non-Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, Kingella spp. (HACEK group) Gram-negative bacilli such as ours.

Increase of 25-hydroxyvitamin D levels after initiation of combination antiretroviral therapy

Although vitamin D deficiency in HIV patients reported worldwide, the mechanisms and the effect of combination antiretroviral therapy (cART) on vitamin D levels are unclear. Patients were 50 male Japanese with HIV who visited Teikyo University Hospital, Tokyo, Japan. Patients were divided into those receiving cART (cART-experienced group, n = 30) and those who had not received cART (cART-naïve group, n = 20). Patients in the cART-experienced group had received treatment with cART for more than one year and those in the cART-naïve group were just about to start cART at study entry. Patients underwent measurement of serum 25-hydroxyvitamin D (25(OH)D) levels and assessment of clinical factors twice at one year intervals. At study entry, 23 (76.7%) in the cART-experienced group and 19 (95.0%) in the cART-naïve group had vitamin D insufficiency or deficiency. Mean 25(OH)D values were significantly higher in the cART-experienced group (25.2 ng/ml vs. 19.3 ng/ml, p = 0.01). However, levels of 25(OH)D at one year increased more in the cART-naïve group (-1.1 ng/ml vs. 5.0 ng/ml, p = 0.01), with mean 25(OH)D values in the cART-naïve group increasing to match those in the cART-experienced group. HIV infected patients who initiated cART showed increases in vitamin D levels in one year.

Prevalence and risk factors for loss of bone mineral density in male Japanese patients with HIV.

To the Editors: As the mortality of HIV-infected individuals was improved by combination antiretroviral therapy (cART), opportunistic infections were replaced by long-term complications including loss of bone mineral density (BMD). It was first reported in 1999 and has emerged in the last decade and has probably placed HIV-infected individuals at higher risk of bone fractures. The causes are considered to be multifactorial and include HIV infection itself, body mass index (BMI), estimated glomerular filtration rate (eGFR), testosterone level, and hepatitis coinfection. Some articles link the use of protease inhibitors and the tenofovir (TDF) with lower BMD. Most of the articles associated with BMD loss in HIV-infected patients have been reported from North America, Europe, and Oceania. Accordingly, the BMD research on HIV-infected Asians is underrepresented. In this work, we focused on male Japanese HIV-infected patients and studied the prevalence and severity of BMD loss among them and attempted to determine clinical factors related to BMD loss. Forty male Japanese HIV-infected individuals aged from 21 to 70 years who visited the Teikyo University Hospital were enrolled in this study. This study was approved by the ethical committee of the Teikyo University School of Medicine, and the patients gave written informed consent. The patients underwent BMD analyses from March 2010 to February 2012 with the same dual energy X-ray absorptiometry scan (Discovery SI, Hologic Inc, Bedford, MA). Thirty-nine patients were analyzed in both the lumbar spines and bilateral femoral necks, whereas 1 patient was limited to the bilateral femoral necks. The BMD data of the lumbar spines and the smaller BMD value of the femoral necks were employed to calculate T-scores that were calculated as comparison with young normal reference value expressed as SD units. Osteopenia was defined as a T-score of between −1 and −2.5SD, and osteoporosis was defined as that of

Nosocomial bacteremia due to Kluyvera cryocrescens: Case report and literature review

−2.5 negative score following the World Health Organization classification. Clinical factors were collected including age, height, body weight, BMI, smoking status, use of corticosteroid, CD4 cell counts, durations of cART, medication of nucleoside/nucleotide reverse transcriptase inhibitors, serum creatinine, bone alkaline phosphatase (BAP), eGFR, serum, and urine N-terminal telopeptide (NTx). The eGFR for Japanese male patients were calculated by 194 · serum creatinine−1.094 · age−0.287 (mL/min per 1.73 m2). To determine the high-risk groups, statistical differences of T-scores were calculated by using Wilcoxon signed ranks or Kruskal–Wallis test with the post hoc comparisons by the Dunnett test. The correlations between T-scores and each variable were examined by a linear regression employing the method of least squares. A multiple regression analysis was conducted by employing these variables with a P value ,0.1 to predict BMD loss. All the analyses were performed by JMP version 8.0.1 (SAS Institute Inc, United States). The median age of the patients was 39 years. Their median height and body weight were 169.3 cm and 65.0 kg, respectively. Twenty-three patients were #170 cm, and 14 were ,60 kg. The median CD4 count was 396/mL. Twenty-seven were on cART, and median duration of cART was 2.9 years. Five have been continued on cART for .10 years. Twelve out of 27 took TDF/emtricitabine (FTC), and 13 took abacavir/lamivudine (3TC). The median and interquartile ranges of BMD and T-scores in the lumbar spines and the femoral necks are summarized in Table 1. The median T-scores in the lumbar spines and the femoral necks were −0.8 and −1.2, respectively. The T-scores of the femoral necks were significantly lower than those of the lumbar spines (P = 0.0461). By employing the T-scores in the lumbar spines, the prevalence of osteopenia and osteoporosis was found to be 43.6% and 5.1%, respectively, and these percentages rose to 47.5% and 7.5%, respectively, if the least T-scores in the femoral necks were used. Moreover, the number (and percentage) of patients with osteopenia and osteoporosis were 21 (52.5%) and 4 (10%), respectively, in at least 1 of the T-score measured in the lumbar spines or in the femoral necks. Subgroup analyses of patients’ baseline characteristics revealed that the group of patients aged 50 years or older was the only group that showed significantly lower T-scores of the lumbar spines. In contrast, high-risk groups that showed significantly lower T-scores of the femoral necks were patients aged 40 years or older, #170 cm in height, weighed #60 kg, those on cART, particularly those continuing cART for

Multifocal Cellulitis due to Disseminated Neisseria Gonorrhoeae in a Male Patient

10 years. There were no significant differences between the 2 groups divided based on the medication of nucleotide reverse transcriptase inhibitors or use of corticosteroid.

Liver Abscess With a Markedly High Level of Carbohydrate Antigen 19-9

Kluyvera cryocrescens infection has been considered rare; clinical features of K. cryocrescens bacteremia remain unclear because few reports have been published. We report a case of K. cryocrescens bacteremia in an adult male patient and review the literature. Our case was one with nosocomial bacteremia in a patient with interstitial lung disease. The primary infection site was undetermined, although he had an indwelling peripheral intravenous catheter and a urinary catheter. Piperacilin/tazobactam was administered for 2 weeks and the bacteremia resolved. Unfortunately, there was acute exacerbation of the interstitial lung disease, which was fatal. According to our review, including our case, K. cryocrescens bacteremia tends to occur in immunocompromised hosts, and indwelling catheters might be risk factors. Extended spectrum cephalosporins, carbapenems, fluoroquinolones and tetracyclines are generally adequate agents for empiric therapy based on susceptibilities of K. cryocrescens clinical isolates.