CD4 cell count and the risk of AIDS or death in HIV-Infected adults on combination antiretroviral therapy with a suppressed viral load: a longitudinal cohort study from COHERE.

BACKGROUND: Most adults infected with HIV achieve viral suppression within a year of starting combination antiretroviral therapy (cART). It is important to understand the risk of AIDS events or death for patients with a suppressed viral load. METHODS AND FINDINGS: Using data from the Collaboration of Observational HIV Epidemiological Research Europe (2010 merger), we assessed the risk of a new AIDS-defining event or death in successfully treated patients. We accumulated episodes of viral suppression for each patient while on cART, each episode beginning with the second of two consecutive plasma viral load measurements 500 copies/µl, the first of two consecutive measurements between 50-500 copies/µl, cART interruption or administrative censoring. We used stratified multivariate Cox models to estimate the association between time updated CD4 cell count and a new AIDS event or death or death alone. 75,336 patients contributed 104,265 suppression episodes and were suppressed while on cART for a median 2.7 years. The mortality rate was 4.8 per 1,000 years of viral suppression. A higher CD4 cell count was always associated with a reduced risk of a new AIDS event or death; with a hazard ratio per 100 cells/µl (95% CI) of: 0.35 (0.30-0.40) for counts <200 cells/µl, 0.81 (0.71-0.92) for counts 200 to <350 cells/µl, 0.74 (0.66-0.83) for counts 350 to <500 cells/µl, and 0.96 (0.92-0.99) for counts ≥500 cells/µl. A higher CD4 cell count became even more beneficial over time for patients with CD4 cell counts <200 cells/µl. CONCLUSIONS: Despite the low mortality rate, the risk of a new AIDS event or death follows a CD4 cell count gradient in patients with viral suppression. A higher CD4 cell count was associated with the greatest benefit for patients with a CD4 cell count <200 cells/µl but still some slight benefit for those with a CD4 cell count ≥500 cells/µl

Role of MicroRNA Profile Modifications in Hepatitis C Virus-Related Mixed Cryoglobulinemia

Hepatitis C virus infection is closely related to lymphoproliferative disorders (LPDs), including mixed cryoglobulinemia (MC) and some lymphomas. Modification of the expression of specific microRNAs (miRNAs) has been associated with different autoimmune diseases and/or LPDs. No data exist about the modifications in miRNA expression in HCV-associated LPDs. The aim of this study was to analyze the expression levels of a panel of miRNAs previously associated with autoimmune/LPDs in a large population of HCV patients with and without MC or non-Hodgkin’s lymphoma (NHL), to identify potential markers of evolution of HCV infection. PBMC expression of miR-Let-7d, miR-16, miR-21, miR-26b, miR-146a and miR-155 was evaluated by real-time PCR in 167 HCV patients (75 with MC [MC-HCV], 11 with HCV-associated NHL [NHL-HCV], 81 without LPD [HCV]) and in 35 healthy subjects (HS). A significant increase in miR-21 (p<0.001), miR-16 (p<0.01) and miR-155 (p<0.01) expression was detected in PBMCs from only NHL patients whereas a significant decrease in miR-26b was detected in both MC and NHL subjects (p<0.01) when compared to HS and HCV groups. A restoration of miR-26b levels was observed in the post-treatment PBMCs of 35 HCV-MC patients experiencing complete virological and clinical response following antiviral therapy. This study, for the first time, shows that specific microRNAs in PBMC from HCV patients who developed MC and/or NHL are modulated differently. The specific, reversible downregulation of miR-26b strongly suggests the key role it plays in the pathogenesis of HCV-related LPDs and its usefulness as a biomarker of the evolution of HCV infection to these disorders

Alzheimers Dement

INTRODUCTION: The clinical relevance of brain atrophy subtypes categorization in non-demented persons without a priori knowledge regarding their amyloid status or clinical presentation is unknown. METHODS: A total of 2083 outpatients with either subjective cognitive complaint or mild cognitive impairment at study entry were followed during 4 years (MEMENTO cohort). Atrophy subtypes were defined using baseline magnetic resonance imaging (MRI) and previously described algorithms. RESULTS: Typical/diffuse atrophy was associated with faster cognitive decline and the highest risk of developing dementia and Alzheimer's disease (AD) over time, both in the whole analytic sample and in amyloid-positive participants. Hippocampal-sparing and limbic-predominant atrophy were also associated with incident dementia, with faster cognitive decline in the limbic predominant atrophy group. Lewy body dementia was more frequent in the hippocampal-sparing and minimal/no atrophy groups. DISCUSSION: Atrophy subtypes categorization predicted different subsequent patterns of cognitive decline and rates of conversion to distinct etiologies of dementia in persons attending memory clinics

Waist circumference and waist/hip ratio are better predictive risk factors for mortality and morbidity after colorectal surgery than body mass index and body surface area

Objectives: To determine whether body fat distribution, measured by waist circumference (WC) and waist/hip ratio (WHR), is a better predictor of mortality and morbidity after colorectal surgery than body mass index (BMI) or body surface area (BSA). Background: Obesity measured by BMI is not a consistent risk factor for postoperative mortality and morbidity after abdominal surgery. Studies in metabolic and cardiovascular diseases have shown WC and WHR to be better outcome predictors than BMI. Methods: A prospective multicenter international study was conducted among patients undergoing elective colorectal surgery. The WHR, BMI, and BSA were derived from body weight, height, and waist and hip circumferences measured preoperatively. Uni- and multivariate analyses were performed to identify risk factors for postoperative outcomes. Results: A total of 1349 patients (754 men) from 38 centers in 11 countries were included. Increasing WHR significantly increased the risk of conversion [odds ratio (OR) = 15.7, relative risk (RR) = 4.1], intraoperative complications (OR = 11.0, RR = 3.2), postoperative surgical complications (OR = 7.7, RR = 2.0), medical complications (OR = 13.2, RR = 2.5), anastomotic leak (OR = 13.7, RR = 3.3), reoperations (OR = 13.3, RR = 2.9), and death (OR = 653.1, RR = 21.8). Both BMI (OR = 39.5, RR = 1.1) and BSA (OR = 4.9, RR = 3.1) were associated with an increased risk of abdominal wound complication. In multivariate analysis, the WHR predicted intraoperative complications, conversion, medical complications, and reinterventions, whereas BMI was a risk factor only for abdominal wall complications; BSA did not reach significance for any outcome. Conclusions: The WHR is predictive of adverse events after elective colorectal surgery. It should be used in routine clinical practice and in future risk-estimating systems. Keywords: body mass index, body surface area, colorectal surgery, morbimortality, waist/hip rati