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

Gas Sensing Properties of NiSb 2

Micro- and nanoparticles of NiSb2O6 were synthesized by the microwave-assisted colloidal method. Nickel nitrate, antimony chloride, ethylenediamine, and ethyl alcohol were used. The oxide was obtained at 600°C and was analyzed by X-ray diffraction (XRD) and Raman spectroscopy, showing a trirutile-type structure with cell parameters a = 4.641 Å, c = 9.223 Å, and a space group P42/mnm (136). Average crystal size was estimated at ~31.19 nm, according to the XRD-peaks. The microstructure was scrutinized by scanning electron microscopy (SEM), observing microrods measuring ~3.32 μm long and ~2.71 μm wide, and microspheres with an average diameter of ~8 μm; the size of the particles shaping the microspheres was measured in the range of ~0.22 to 1.8 μm. Transmission electron microscopy (TEM) revealed that nanoparticles were obtained with sizes in the range of 2 to 20 nm (~10.7 nm on average). Pellets made of oxide’s powders were tested in propane (C3H8) and carbon monoxide (CO) atmospheres at different concentrations and temperatures. The response of the material increased significantly as the temperature and the concentration of the test gases rose. These results show that NiSb2O6 may be a good candidate for gas sensing applications

613 cases of splenic rupture without risk factors or previously diagnosed disease: a systematic review

Background Rupture of the spleen in the absence of trauma or previously diagnosed disease is largely ignored in the emergency literature and is often not documented as such in journals from other fields. We have conducted a systematic review of the literature to highlight the surprisingly frequent occurrence of this phenomenon and to document the diversity of diseases that can present in this fashion. Methods Systematic review of English and French language publications catalogued in Pubmed, Embase and CINAHL between 1950 and 2011. Results We found 613 cases of splenic rupture meeting the criteria above, 327 of which occurred as the presenting complaint of an underlying disease and 112 of which occurred following a medical procedure. Rupture appeared to occur spontaneously in histologically normal (but not necessarily normal size) spleens in 35 cases and after minor trauma in 23 cases. Medications were implicated in 47 cases, a splenic or adjacent anatomical abnormality in 31 cases and pregnancy or its complications in 38 cases. The most common associated diseases were infectious (n = 143), haematologic (n = 84) and non-haematologic neoplasms (n = 48). Amyloidosis (n = 24), internal trauma such as cough or vomiting (n = 17) and rheumatologic diseases (n = 10) are less frequently reported. Colonoscopy (n = 87) was the procedure reported most frequently as a cause of rupture. The anatomic abnormalities associated with rupture include splenic cysts (n = 6), infarction (n = 6) and hamartomata (n = 5). Medications associated with rupture include anticoagulants (n = 21), thrombolytics (n = 13) and recombinant G-CSF (n = 10). Other causes or associations reported very infrequently include other endoscopy, pulmonary, cardiac or abdominal surgery, hysterectomy, peliosis, empyema, remote pancreato-renal transplant, thrombosed splenic vein, hemangiomata, pancreatic pseudocysts, splenic artery aneurysm, cholesterol embolism, splenic granuloma, congenital diaphragmatic hernia, rib exostosis, pancreatitis, Gaucher's disease, Wilson's disease, pheochromocytoma, afibrinogenemia and ruptured ectopic pregnancy. Conclusions Emergency physicians should be attuned to the fact that rupture of the spleen can occur in the absence of major trauma or previously diagnosed splenic disease. The occurrence of such a rupture is likely to be the manifesting complaint of an underlying disease. Furthermore, colonoscopy should be more widely documented as a cause of splenic rupture

Putative mechanisms and biological role of coccoid form formation in Campylobacter jejuni.

In certain conditions Campylobacter jejuni cells are capable of changing their cell shape from a typically spiral to a coccoid form (CF). By similarity to other bacteria, the latter was initially considered to be a viable but non-culturable form capable of survival in unfavourable conditions. However, subsequent studies with C. jejuni and closely related bacteria Helicobacter pylori suggested that CF represents a non-viable, degenerative form. Until now, the issue on whether the CF of C. jejuni is viable and infective is highly controversial. Despite some preliminary experiments on characterization of CF cells, neither biochemical mechanisms nor genetic determinants involved in C. jejuni cell shape changes have been characterized. In this review, we highlight known molecular mechanisms and genes involved in CF formation in other bacteria. Since orthologous genes are also present in C. jejuni, we suggest that CF formation in these bacteria is also a regulated and genetically determined process. A possible significance of CF in the lifestyle of this important bacterial pathogen is discussed

The evolution of living beings started with prokaryotes and in interaction with prokaryotes

In natural world, no organism exists in absolute isolation, and thus every organism must interact with the environment and other organisms. Next-generation sequencing technologies are increasingly revealing that most of the cells in the environment resist cultivation in the laboratory and several prokaryotic divisions have no known cultivated representatives. Based on this, we hypothesize that species that live together in the same ecosystem are more or less dependent upon each other and are very large in diversity and number, outnumbering those that can be isolated in single-strain laboratory culture. In natural environments, bacteria and archaea interact with other organisms (viruses, protists, fungi, animals, plants, and human) in complex ecological networks, resulting in positive, negative, or no effect on one or another of the interacting partners. These interactions are sources of ecological forces such as competitive exclusion, niche partitioning, ecological adaptation, or horizontal gene transfers, which shape the biological evolution. In this chapter, we review the biological interactions involving prokaryotes in natural ecosystems, including plant, animal, and human microbiota, and give an overview of the insights into the evolution of living beings. We conclude that studies of biological interactions, including multipartite interactions, are sources of novel knowledge related to the biodiversity of living things, the functioning of ecosystems, the evolution of the cellular world, and the ecosystem services to the living beings