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

Identificación de fases portadoras y flujos de mercurio en el registro sedimentario de la Laguna del Plata, región central de Argentina

En este trabajo se analiza la variación en las concentraciones de mercurio, las fases portadoras del mismo y los flujos de este elemento producidos en la Laguna del Plata, en la región central de Argentina, en los últimos 80 años, aproximadamente. Para ello se realizaron análisis químicos, mineralógicos, sedimentológicos y dataciones radiométricas en un núcleo de sedimento de 120 cm de profundidad extraído de la Laguna del Plata y de sedimentos de lecho tomados a lo largo de toda la cuenca del río Suquía que desemboca en la mencionada laguna. La determinación de mercurio total particulado (HgT) se realizó mediante espectrometría de absorción atómica con vapor frío, previa incineración y amalgamación, utilizando un analizador directo de mercurio. Los resultados obtenidos sugieren que las variaciones en los niveles de Hg responden principalmente a cambios hidrológicos registrados en el sistema en los últimos 80 años, más o menos. En el período seco que afectó la región antes de 1968, la principal fuente de Hg fueron los sedimentos transportados desde las cabeceras de la cuenca del río Suquía; esto generó concentraciones de Hg más o menos constantes en la base del núcleo de sedimento, que son además similares a las medidas en los sedimentos del resto de la cuenca. En estos sedimentos, el Hg se encuentra principalmente adsorbido a la pirita y en menor medida asociado con la materia orgánica particulada. El aumento en las precipitaciones de la región a partir de 1968 y hasta 2003 coincide con un aumento en las concentraciones de HgT, probablemente asociado con un mayor arrastre de sedimentos desde las cabeceras de la cuenca y un mayor aporte de Hg atmosférico desde las precipitaciones. En ese período la mayor parte del Hg determinado pareciera ser de tipo geogénico y habría llegado a la laguna adsorbido sobre pirita y óxidos de Fe y Mn presentes en los sedimentos de lecho. Una vez en la laguna, se habría producido una removilización y transporte a partir de diversos procesos biogeoquímicos, que determinaron su asociación preferente con la materia orgánica en los sedimentos acumulados en ese período. El pico de concentración de Hg registrado en sedimentos acumulados entre 1990 y 1995 se atribuye al aporte de las cenizas volcánicas que alcanzaron la región luego de la erupción del volcán Láscar en 1993. Finalmente, en los sedimentos más modernos (acumulados desde 2003) el incremento continuo de las concentraciones de Hg se atribuye a las mencionadas fuentes geogénicas y al aumento de los flujos globales de Hg atmosférico.In this work the variations in the concentrations of mercury, the carrying phases and fluxes in the last ~80 years are anal yzed for the sedimentary record of the Laguna del Plata. Chemical, mineralogical and sedimentological analysis were performed, as well as radiometric dating, of a 120 cm sediment core extracted from Laguna del Plata and sediments collected from the riverbed along the Suquía river basin that discharges into the mentioned lake. Total mercury (HgT) was determined by cold vapour atomic absorption spectrometry after incineration and amalgamation, using a direct mercury analyzer. The results suggest that variations in Hg levels respond mainly to hydrological changes registered in the system in the last ~80 years. During the dry period that affected the region before 1968, the main Hg sources were the sediments transported from the upper Suquía river watershed. Constant Hg concentrations measured at the base of the sedimentary core are similar to those measured in the sediments of the basin, which supports the hypothesis of a contribution from terrigenous Hg. The main Hg-bearing phase determined in these sediments is pyrite and, to a lesser extent, particulate organic matter. The rise in the regional precipitation from 1972 to 2003 coincides with an increase in HgT concentrations, probably associated to an increased sediment transport from the upper part of the basin and to higher atmospheric Hg input from precipitation. In that period, Hg probably reached the lake adsorbed into pyrite and Fe and Mn-(hydr) oxides present in the riverbed sediments. Once in the lake, subsequent remobilization and transport through various biogeochemical processes would have occurred, which explains its association with organic matter in sediments accumulated in that period. The peak of Hg concentrations registered in sediments accumulated between 1990 and 1995 is attributed to the contribution from volcanic ash that reached the region after the eruption of the Lascar volcano in 1993. Finally, in the most recent sediments (accumulated since 2003) the steady increase in Hg concentrations is attributed to the mentioned geogenic sources, but also to the increase of global atmospheric Hg fluxes.Fil: Stupar, Yohana Vanesa. Universite de Bordeaux; FranciaFil: Garcia, Maria Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Ciencias de la Tierra; ArgentinaFil: Schäfer, Jörg. Universite de Bordeaux; Francia. Centre National de la Recherche Scientifique; FranciaFil: Schmidt, Sabine. Universite de Bordeaux; Francia. Centre National de la Recherche Scientifique; FranciaFil: Piovano, Eduardo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Ciencias de la Tierra; ArgentinaFil: Blanc, Gérard. Universite de Bordeaux; Francia. Centre National de la Recherche Scientifique; FranciaFil: Huneau, Fréderic. Université de Corse Pascal Paoli; Francia. Centre National de la Recherche Scientifique; FranciaFil: Le Coustumer, Phillipe. Universite de Bordeaux; Franci

Endoscopic treatment of fistula after sleeve gastrectomy: results of a multicenter retrospective study

International audienceBACKGROUND AND STUDY AIMS:Fistula is the main complication of laparoscopic sleeve gastrectomy (LSG), for which healing is difficult to achieve. The aims of the study were to evaluate the efficacy of interventional endoscopy for post-LSG fistula treatment, to evaluate various endoscopic techniques used and identify their complications, and to identify predictive factors of healing following endoscopic treatment.PATIENTS AND METHODS:This retrospective multicenter study included patients with post-LSG fistula. Therapeutic procedures were evaluated, taking into account complications and healing times. Endoscopic procedures were considered to have promoted healing if no other surgical procedure was performed. Predictive factors of healing were identified by univariate and multivariate analysis.RESULTS:A total of 110 patients were included, of whom 6 (5.5 %) healed spontaneously, 81 (73.6 %) healed following endoscopic treatment, and 19 (17.3 %) healed following surgery. Healing rates following endoscopic treatment were 84.4 % in the first 6 months of treatment (65/77), 52.4 % for treatment lasting 6 - 12 months (11/21), and 41.7 % after 12 months of treatment (5/12). A drainage procedure (surgical, endoscopic, or percutaneous) was performed in 92 patients (83.6 %). A total of 177 esogastric stents were placed in 88 patients (80.0 %). Surgical debridement, clip placement, glue sealing, and plug placement were also performed. Multivariate analysis identified four predictive factors of healing following endoscopic treatment: interval < 21 days between fistula diagnosis and first endoscopy (P = 0.003), small fistula (P = 0.01), interval between LSG and fistula ≤ 3 days (P = 0.01), no history of gastric banding (P = 0.04).CONCLUSION:Endoscopic treatment facilitated healing of post-LSG fistula in 74 % of patients. Early endoscopic treatment increased the likelihood of success, and was most effective during the first 6 months of management. After this point, surgical treatment should be considered.Fistula is the main complication of laparoscopic sleeve gastrectomy (LSG), for which healing is difficult to achieve. The aims of the study were to evaluate the efficacy of interventional endoscopy for post-LSG fistula treatment, to evaluate various endoscopic techniques used and identify their complications, and to identify predictive factors of healing following endoscopic treatment

Position statement on the diagnosis and management of premature/primary ovarian insufficiency (except Turner Syndrome)

International audiencePremature ovarian insufficiency (POI) is a rare pathology affecting 1-2% of under-40 year-old women, 1 in 1000 under-30 year-olds and 1 in 10,000 under-20 year-olds. There are multiple etiologies, which can be classified as primary (chromosomal, genetic, auto-immune) and secondary or iatrogenic (surgical, or secondary to chemotherapy and/or radiotherapy). Despite important progress in genetics, more than 60% of cases of primary POI still have no identifiable etiology; these cases are known as idiopathic POI. POI is defined by the association of 1 clinical and 1 biological criterion: primary or secondary amenorrhea or spaniomenorrhea of>4 months with onset before 40 year of age, and elevated follicle-stimulating hormone (FSH)>25IU/L on 2 assays at>4 weeks' interval. Estradiol level is low, and anti-Müllerian hormone (AMH) levels have usually collapsed. Initial etiological work-up comprises auto-immune assessment, karyotype, FMR1 premutation screening and gene-panel study. If all of these are normal, the patient and parents may be offered genome-wide analysis under the "France Génomique" project. The term ovarian insufficiency suggests that the dysfunction is not necessarily definitive. In some cases, ovarian function may fluctuate, and spontaneous pregnancy is possible in around 6% of cases. In confirmed POI, hormone replacement therapy is to be recommended at least up to the physiological menopause age of 51 years. Management in a rare diseases center may be proposed