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Objectives HIV-infected individuals are at increased risk of incident fractures. Evaluation of trabecular bone micro-architecture is an important tool to assess bone strength, but its use has not yet been reported in middle-aged HIV-infected male individuals. The aim of the study was to compare bone micro-architecture between HIV-infected and HIV-uninfected men. Methods In this cross-sectional study, 53 HIV-infected male individuals with a mean (± standard deviation) age of 49 ± 9 years who had been receiving antiretroviral therapy including tenofovir disoproxil fumarate ( DF) for at least 60 months were compared with 50 HIV-uninfected male controls, matched for age and ethnic origin. We studied the volumetric bone density and micro-architecture of the radius and tibia using high-resolution peripheral quantitative computed tomography ( HR-p QCT). Results Volumetric trabecular bone density was 17% lower in the tibia ( P < 10−4) and 16% lower in the radius ( P < 10−3) in HIV-infected patients compared with controls. By contrast, the cortical bone density was normal at both sites. The tibial trabecular micro-architecture differed markedly between patients and controls: bone volume/total volume ( BV/ TV) and trabecular number were each 13% lower ( P < 10−4 for both). Trabecular separation and inhomogeneity of the network were 18% and 24% higher in HIV-infected patients than in controls, respectively. The radial BV/ TV and trabecular thickness were each 13% lower ( P < 10−3 and 10−2, respectively). Cortical thickness was not different between the two groups. Conclusions The findings of lower volumetric trabecular bone density and disrupted trabecular micro-architectural parameters in middle-aged male HIV-infected treated patients help to explain bone frailty in these patients. [ABSTRACT FROM AUTHOR]

Narlaprevir, a hepatitis C virus (HCV) NS3/4A serine protease inhibitor, has demonstrated robust antiviral activity in a placebo-controlled phase 1 study. To study evolutionary dynamics of resistant variants, the NS3 protease sequence was clonally analysed in thirty-two HCV genotype 1-infected patients following treatment with narlaprevir. Narlaprevir monotherapy was administered for one week (period 1) followed by narlaprevir/pegylated interferon-alpha-2b combination therapy with or without ritonavir (period 2) during two weeks, interrupted by a washout period of one month. Thereafter, all patients initiated pegylated interferon-alpha-2b/ribavirin combination therapy. Longitudinal clonal analysis was performed in those patients with NS3 mutations. After narlaprevir re-exposure, resistance-associated mutations at position V36, T54, R155 and A156 were detected in five patients in >95% of the clones. Narlaprevir retreatment resulted in a 2.58 and 5.06 log10 IU/mL viral load decline in patients with and without mutations, respectively ( P = <0.01). After treatment, resistant variants were replaced with wild-type virus within 2-24 weeks in three patients. However, the R155K mutation was still observed 3.1 years after narlaprevir dosing in two patients in 5% and 45% of the viral population. Resistant variants could be detected early during treatment with narlaprevir. A slower viral load decline was observed in those patients with resistance-associated mutations detectable by direct population sequencing. These mutations disappeared within six months following treatment with the exception of R155K mutation, which persisted in two patients. [ABSTRACT FROM AUTHOR]

To assess the antiviral response to optimized therapy following genotypic resistance testing and to identify factors associated with virological response in HIV-1-infected patients failing antiretroviral therapy.A prospective cohort study was conducted in 344 HIV-1-infected patients who underwent genotypic resistance testing because of virological failure. Virological response was defined as a plasma HIV RNA level below 200 HIV-1 RNA copies/mL or a drop of plasma viral load from baseline of more than 1 log10. A multivariate logistic regression analysis was performed to identify factors associated with virological response.The median age of the patients was 40 years, with a male to female ratio of 4:1. Fifty-one per cent of patients had received the three major classes of antiretrovirals and the median duration of previous antiretroviral therapy was 4.6 years. At baseline, the median plasma HIV RNA level was 4.4 log10 copies/mL and the median CD4 cell count was 274 cells/μL. At 3 months, 55% of patients (188 of 344) had a virological response, which was sustained at 6 months (53%). Predictors of virological response were exposure to two or fewer protease inhibitors [odds ratio (OR) 1.8;P=0.046], and use in optimized therapy of a new class of antiretrovirals (OR 2.9;P=0.006), of more than two new drugs (OR 3.0;P<0.0001), of abacavir (OR 1.9;P=0.03), or of lopinavir/ritonavir (OR 3.7;P=0.0002).A high proportion of patients achieved a short-term virological response in this cohort study. Patients with the least experience of protease inhibitor treatment and in whom a new class of antiretroviral, more than two new drugs, abacavir or lopinavir/ritonavir was used in optimized therapy had the best virological outcome. [ABSTRACT FROM AUTHOR]

Spontaneous remission of acute myeloid leukemia in the adult is a rare event. We report on a 31-year-old male patient suffering from acute myeloid leukemia (AML) M5a according to the French-American-British (FAB) classification with biphenotypic features in flow cytometric examination and severe bacterial infection with group G streptococci at the time of diagnosis. Because of sepsis and stable clinical conditions, chemotherapy was delayed and antibiotics were administered intravenously. Within 6 weeks a spontaneous remission of AML occurred. Remission lasted for about 2 months. At the time of relapse, a change in phenotype of the leukemic blasts with a loss of B-lymphoid markers could be demonstrated by flow cytometry. The patient was treated with an induction therapy according to the multicentric German AMLCG 2000 schedule. To our knowledge, this is the first report of a spontaneous remission in an AML FAB M5a associated with coexpression of myeloid- and lymphoid-associated antigens on the leukemic blasts. Possible mechanisms of this phenomenon are discussed with a review of the literature. [ABSTRACT FROM AUTHOR]

Although numerous diseases may mimic or be confused with irritable bowel syndrome (IBS), a detailed and precise clinical history and a normal clinical examination usually lead to an accurate diagnosis of IBS. The presence of symptom criteria and the absence of warning signs must be established. Before entering a clinical trial, several routine tests are generally required: total blood count, erythrocyte sedimentation rate, biochemistry screen, stool culture and examination for occult blood, ova, and parasites, and a recent (<2 years) normal flexible sigmoidoscopy or colonoscopy with biopsy. Blood and stool tests are not necessary for the diagnosis of IBS but are important in the framework of controlled trials. Esophagogastroduodenoscopy, abdominal ultrasonography, and malabsorption tests are needed only in patients with atypical IBS or for phase II trials in certain subgroups of patients. Chronic diseases, drugs, and toxic agents that may mimic IBS symptoms or exacerbate the disorder must be excluded. Errors in patient inclusion will be minimized if the duration and severity of IBS symptoms before inclusion is sufficient and will have little effect on the result of the trial if the new drug is really effective and the study well randomized with a correct calculation of sample size. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor of "Leukemia" journal commenting on the successful treatment of hyperuricemia in patients with hematologic malignancy and tumor lysis syndrome.

Abstract: The quality of a therapeutic trial depends on several parameters. The ideal trial in prostate cancer should be a high-quality trial on a well-defined and significant population. The method used to calculate the number of subjects necessary should appear in the study. There should be a single and significant evaluation criterion and follow-up should be long given the natural history of the disease. Intention to treat is also a quality criterion. Finally, the therapeutic class effect does not exist; therefore, the efficacy of any new drug, must be proven. [Copyright &y& Elsevier]

Abstract: BK-virus is a very common polyomavirus in the global population, similar to the JC-virus responsible for Progressive Multifocal Leukoencephalopathy. BK-virus infections are an important diagnostic and therapeutic challenge in immuno-compromised patients, including: bone marrow transplant pediatric recipients in whom it may cause hemorrhagic cystitis, renal transplant recipients in whom it may cause interstitial nephropathy leading to graft loss, and in HIV infected patients in whom it may cause some types of encephalitis. Indeed, this poorly documented virus is responsible for infections with various clinical profiles, probably under-diagnosed, but could also be involved in the genesis of some cancers, especially cervix and prostate cancer. We reviewed the latest published data on this virus focusing on its possible pro-oncogenic properties. We also listed the diseases in which it is involved, with an emphasis on rare and insufficiently investigated entities. Finally, we studied the new tools available for diagnosis and treatment, and their importance in current practice. [Copyright &y& Elsevier]