Circulating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection: A case control study

Introduction: The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods: A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results: None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR- 145 correlated with nadir CD4+ T cell count. Discussion: No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection

Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe

Normal values of Wiberg's lateral center-edge angle and Lequesne's acetabular index--a coxometric update

BACKGROUND: The historical pathological cut-off values for Wiberg's lateral center-edge (LCE) angle and Lequesne's acetabular index (AI) are below 20° and above 12° for the LCE and AI, respectively. The aim of this study was to reassess these two angles more than 50 years after their introduction using a standardized conventional radiological measurement method, considering changing social habits and their associated physiological changes. METHODS: A total of 1,226 anteroposterior radiographs of the pelvis (2,452 hips) were obtained according to a strict standardized radiographic technique allowing reliable measurements of the LCE angle and the AI. RESULTS: Distributions of the LCE and AI were pronouncedly Gaussian, with mean values of 33.6° for the LCE and 4.4° for the AI. The 2.5th and 97.5th empirical percentiles were 18.1 and 48.0° for the LCE and -6.9 and 14.9° for the AI. These intervals contained 95 % of the data in our large sample. Small but statistically significant differences between the sexes and right and left hips have been demonstrated. Correlation between age and coxometric indices was low. CONCLUSION: The above findings do not conflict with the historical benchmarks. Statistical differences between sexes and between right and left hips were not clinically relevant. No conclusion can be drawn about coxometric indices and clinical manifestations of hip dysplasia

Acetabular fracture types vary with different acetabular version

PURPOSE: Acetabular fractures typically occur in high energy trauma. Understanding of the various contributing biomechanical factors and trauma mechanisms is still limited. While several investigations figured out what role femoral position during impact plays in distinct fracture patterns, no data exists on the influence of acetabular version on the fracture type. Our study was carried out to clarify this issue. METHODS: Radiological data sets of 192 patients (145 male, 47 female, age 14-90 years) sustaining acetabular fractures were assessed retrospectively. The crossover ratio of the crossover sign and presence or absence of the posterior wall sign and ischial spine sign were used to determine acetabular retroversion on conventional radiographs. Acetabular version in the axial plane was measured on a computed tomography (CT) scan. Statistics were then performed to analyse the relationship between the acetabular fracture type according to the Letournel classification and acetabular version. RESULTS: A significant difference (p = 0.029) in acetabular version was found between fractures of the anterior [mean equatorial edge (EE) angle 19.93°] and posterior (mean EE angle 17.53°) acetabulum in the CT scan. No difference was shown on the measurements on conventional radiographs. CONCLUSIONS: Acetabular version in the axial plane has an influence on the acetabular fracture pattern. While more anteverted acetabula were frequently associated with anterior fracture types according to the Letournel classification, retroversion of the acetabulum was associated with posterior fracture types