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

Evaluating ecosystem effects of climate change on tropical island streams using high spatial and temporal resolution sampling regimes

Climate change is expected to alter precipitation patterns worldwide, which will affect streamflow in riverine ecosystems. It is vital to understand the impacts of projected flow variations, especially in tropical regions where the effects of climate change are expected to be one of the earliest to emerge. Space-for-time substitutions have been successful at predicting effects of climate change in terrestrial systems by using a spatial gradient to mimic the projected temporal change. However, concerns have been raised that the spatial variability in these models might not reflect the temporal variability. We utilized a well-constrained rainfall gradient on Hawaii Island to determine (a) how predicted decreases in flow and increases in flow variability affect stream food resources and consumers and (b) if using a high temporal (monthly, four streams) or a high spatial (annual, eight streams) resolution sampling scheme would alter the results of a space-for-time substitution. Declines in benthic and suspended resource quantity (10- to 40-fold) and quality (shift from macrophyte to leaf litter dominated) contributed to 35-fold decreases in macroinvertebrate biomass with predicted changes in the magnitude and variability in the flow. Invertebrate composition switched from caddisflies and damselflies to taxa with faster turnover rates (mosquitoes, copepods). Changes in resource and consumer composition patterns were stronger with high temporal resolution sampling. However, trends and ranges of results did not differ between the two sampling regimes, indicating that a suitable, well-constrained spatial gradient is an appropriate tool for examining temporal change. Our study is the first to investigate resource to community wide effects of climate change on tropical streams on a spatial and temporal scale. We determined that predicted flow alterations would decrease stream resource and consumer quantity and quality, which can alter stream function, as well as biomass and habitat for freshwater, marine, and terrestrial consumers dependent on these resources

Radiological differentiation of optic neuritis with myelin oligodendrocyte glycoprotein antibodies, aquaporin-4 antibodies, and multiple sclerosis

Recognizing the cause of optic neuritis (ON) affects treatment decisions and visual outcomes.We aimed to define radiological features of first-episode demyelinating ON.We performed blinded radiological assessment of 50 patients presenting with first-episode myelin oligodendrocyte glycoprotein (MOG) antibody-associated ON (MOG-ON; n=19), aquaporin-4 (AQP4) antibody-associated ON (AQP4-ON; n=11), multiple sclerosis (MS)-associated ON (MS-ON; n=13), and unclassified ON (n=7).Bilateral involvement was more common in MOG-ON and AQP4-ON than MS-ON (84% vs. 82% vs. 23%), optic nerve head swelling was more common in MOG-ON (53% vs. 9% vs. 0%), chiasmal involvement was more common in AQP4-ON (5% vs. 64% vs. 15%), and bilateral optic tract involvement was more common in AQP4-ON (0% vs. 45% vs. 0%). Retrobulbar involvement was more common in MOG-ON, whereas intracranial involvement was more common in AQP4-ON. MOG-ON and AQP4-ON had longer lesion lengths than MS-ON. The combination of two predictors, the absence of magnetic resonance imaging brain abnormalities and a higher lesion extent score, showed a good ability to discriminate between an autoantibody-associated ON (MOG or AQP4) and MS. AQP4-ON more frequently had severe and sustained visual impairment.MOG-ON and AQP4-ON are more commonly bilateral and longitudinally extensive. MOG-ON tends to involve the anterior optic pathway, whereas AQP4-ON the posterior optic pathway

Clinical characteristics of subependymal giant cell astrocytoma in tuberous sclerosis complex

International audienceBackground: This study evaluated the characteristics of subependymal giant cell astrocytoma (SEGA) in patients with tuberous sclerosis complex (TSC) entered into the TuberOus SClerosis registry to increase disease Awareness (TOSCA). Methods: The study was conducted at 170 sites across 31 countries. Data from patients of any age with a documented clinical visit for TSC in the 12 months preceding enrollment or those newly diagnosed with TSC were entered. Results: SEGA were reported in 554 of 2,216 patients (25%). Median age at diagnosis of SEGA was 8 years (range, 18 years. SEGA were symptomatic in 42.1% of patients. Symptoms included increased seizure frequency (15.8%), behavioural disturbance (11.9%), and regression/loss of cognitive skills (9.9%), in addition to those typically associated with increased intracranial pressure. SEGA were significantly more frequent in patients with TSC2 compared to TSC1 variants (33.7 vs. 13.2 %, p < 0.0001). Main treatment modalities included surgery (59.6%) and mammalian target of rapamycin (mTOR) inhibitors (49%). Conclusions: Although SEGA diagnosis and growth typically occurs during childhood, SEGA can occur and grow in both infants and adults