Estudio epidemiológico y genotipificación de virus BK en receptores de trasplante renal

El virus BK pertenece a la familia poliomaviridae. Fue clasificado inicialmente en Subtipos I a IV, de acuerdo a su reactividad antigénica. Posteriormente, al estudiar el genoma viral, sustituciones nucleotídicas en el gen VP1, fueron identificadas como responsables de esa diversidad inmunoserológica, dando lugar a la clasificación molecular en Subtipos I a IV y a la visualización, mediante análisis filogenético , de Subgrupos dentro del Subtipo I, los cuales presentan una estrecha relación con poblaciones humanas de etnias determinadas. No se cuenta en Argentina con estudios de prevalencia de los subgrupos mencionados, a excepción de los previos presentados por nuestro Programa en receptores de trasplante renal, en quienes la nefropatía producida por el virus puede llevar a la pérdida del injerto.Facultad de Ciencias Médica

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

Flexible sigmoidoscopy screening for colorectal cancer in average-risk subjects: A community-based pilot project

Design: Subjects, chosen at random and recruited by mail, were examined by flexible sigmoidoscopy. Participants and setting: Normal-risk, asymptomatic men and women aged 55-59 years recruited from the community, July to December, 1995. Main outcome measures: Number of polyps detected and cancers diagnosed, and compliance with screening. Results: Letters of invitation were sent to 3500 subjects; of these, 2881 were eligible for inclusion in the study and 342 (12%) consented to participate. A further 3.5% of non-compliant subjects attended the screening program after a telephone survey assessing reasons for non-attendance. Common reasons for non-attendance were a lack of interest (30%) or a lack of time, mainly due to work commitments (28%). A third of subjects had polyps and 46% of these were adenomas. Three subjects were found to have adenocarcinoma: in two the cancer was confined to a polyp and treated with polypectomy, and one subject underwent anterior resection (overall prevalence of cancer, 0.9%). The median depth of insertion achieved with flexible sigmoidoscopy was 55 cm (range, 25-100 cm). Median pain level (on a scale of 0 = no pain to 10 = worst pain imaginable) was 2 (range, 0-8.5), and 99% of the subjects would have the test again if required. Conclusions: Flexible sigmoidoscopy was well tolerated and had an acceptable detection rate of adenomatous polyps and early cancer. Subject compliance emerged as a major issue which requires further evaluation to maximise participation in future programs

Thermal stability and decomposition mechanism of 1-allylimidazole coordination compounds: a TG-FTIR study of Co(II), Ni(II) and Cu(II) hexacoordinate complexes

A thermoanalytical study of 1-allylimidazole complexes with divalent transition metal ions, such as Co(II), Ni(II) and Cu(II) is reported. The precipitated [ML(6)](NO(3))(2) Octahedral compounds were characterized by elemental analysis and thermo-gravimetry (TG)-FTIR spectroscopy

Distal colonic neoplasms predict proximal neoplasia in average-risk, asymptomatic subjects

Flexible sigmoidoscopy has been recommended as a screening method to reduce the incidence of colorectal cancer in asymptomatic, average-risk subjects through the early detection and removal of polyps. However, the association between distal and proximal colonic neoplasia and, hence, the requirement for colonoscopic follow up of screen-detected distal neoplasms is unclear. Our aims were: (i) to evaluate the risk of having proximal neoplasms in those with distal colonic neoplasms; and (ii) to determine whether the risk was dependent on the number, size, histology or morphology of the distal lesions. We prospectively evaluated asymptomatic subjects in a flexible sigmoidoscopy based screening programme. Those with rectosigmoid neoplasia underwent colonoscopy. The number, size, histology and morphology of the polyps were recorded. Advanced lesions were defined as adenomas > 1 cm or with a villous component or severe dysplasia, carcinoma in situ or cancer. Adenomatous polyps were found in 17% (135) of screening flexible sigmoidoscopies. At colonoscopy, up to 30% of subjects with distal colonic neoplasms had synchronous proximal lesions at colonoscopy and up to 20% had advanced proximal lesions. The risk of proximal colonic neoplasia was increased in those with distal sessile colonic neoplasms but appeared independent of distal lesion size, number or morphology. In conclusion, distal colonic neoplasia predicts proximal neoplasia in up to 30% of subjects and these were advanced lesions in up to 20%. We recommend that all subjects with biopsy proven distal colonic neoplasia undergo colonoscopy

Colorectal cancer screening by general practitioners: Comparison with national guidelines

OBJECTIVE: To determine whether general practitioners (GPs) had received Australian guidelines on early detection, screening and surveillance for colorectal cancer or rectal bleeding, and whether their reported practice conformed with these guidelines. DESIGN: Cross-sectional postal survey of self-reported practice. PARTICIPANTS AND SETTING: 213 GPs in practice in the southern metropolitan area of Perth, Western Australia, were randomly selected from the Fremantle Regional Division of General Practice database and surveyed in March 1997. RESULTS: Replies were received from 155 (73%) of the GPs, and 110 reported receiving guidelines (from the Australian Gastroenterology Institute [AGI], 44; Gut Foundation of Australia [GFA], 40; others, 6; and not specified, 20). GPs who reported receiving guidelines were significantly more likely to screen for colorectal cancer (99/110; 90%) than those who reported not receiving guidelines (33/45; 73%) (P = 0.008). The commonest method to investigate people with identifiable risk factors for colorectal cancer was colonoscopy. Reported screening frequencies in asymptomatic patients with above-average risk (family history of colorectal cancer or past history of adenomatous polyps or colorectal cancer) were significantly higher than recommended by AGI and GFA guidelines (P < 0.05). Up to 24% of GPs investigated altered bowel habit or bleeding per rectum with faecal occult blood testing. CONCLUSIONS: Most GPs report having received guidelines. Reported screening frequency was higher than recommended for most above-average-risk patients, which will result in excessive consumption of resources without benefits for cancer prevention