Bench-to-bedside review: preventive measures for contrast-induced nephropathy in critically ill patients

An increasing number of diagnostic imaging procedures requires the use of intravenous radiographic contrast agents, which has led to a parallel increase in the incidence of contrast-induced nephropathy. Risk factors for development of contrast-induced nephropathy include pre-existing renal dysfunction (especially diabetic nephropathy and multiple myeloma-associated nephropathy), dehydration, congestive heart failure and use of concurrent nephrotoxic medication (including aminoglycosides and amphotericin B). Because contrast-induced nephropathy accounts for a significant increase in hospital-acquired renal failure, several strategies to prevent contrast-induced nephropathy are currently advocated, including use of alternative imaging techniques (for which contrast media are not needed), use of (the lowest possible amount of) iso-osmolar or low-osmolar contrast agents (instead of high-osmolar contrast agents), hyperhydration and forced diuresis. Administration of N-acetylcysteine, theophylline, or fenoldopam, sodium bicarbonate infusion, and periprocedural haemofiltration/haemodialysis have been investigated as preventive measures in recent years. This review addresses the literature on these newer strategies. Since only one (nonrandomized) study has been performed in intensive care unit patients, at present it is difficult to draw firm conclusions about preventive measures for contrast-induced nephropathy in the critically ill. Further studies are needed to determine the true role of these preventive measures in this group of patients who are at risk for contrast-induced nephropathy. Based on the available evidence, we advise administration of N-acetylcysteine, preferentially orally, or theophylline intravenously, next to hydration with bicarbonate solutions

Health-related quality of life among adult HIV positive patients : assessing comprehensive themes and interrelated associations

Acknowledgements We would like to thank all HIV doctors, HIV nurses and clinical nurse specialists for their help with the inclusion of patients in the study. We are further grateful to all patients who filled out the questionnaires.Peer reviewedPublisher PD

Strand-biased defect in C/G transversions in hypermutating immunoglobulin genes in Rev1-deficient mice

Somatic hypermutation of Ig genes enables B cells of the germinal center to generate high-affinity immunoglobulin variants. Key intermediates in somatic hypermutation are deoxyuridine lesions, introduced by activation-induced cytidine deaminase. These lesions can be processed further to abasic sites by uracil DNA glycosylase. Mutagenic replication of deoxyuridine, or of its abasic derivative, by translesion synthesis polymerases is hypothesized to underlie somatic hypermutation

The X-ray warm absorber and nuclear obscuration in the Seyfert 1.8 galaxy ESO 113-G010

We present the first analysis of the X-ray warm absorber and nuclear obscuration in the Seyfert 1.8 galaxy ESO 113-G010. We used archival data from a 100 ks XMM-Newton observation made in 2005. From high resolution spectroscopy analysis of the RGS data, we detect absorption lines originating from a warm absorber consisting of two distinct phases of ionisation, with log xi ~ 3.2 and 2.3 respectively. The higher-ionised component has a larger column density and outflow velocity (N_H ~ 1.6 x 10^22 cm^-2, v ~ -1100 km/s) than the lower-ionised component (N_H ~ 0.5 x 10^22 cm^-2, v ~ -700 km/s). The shape of the optical-UV continuum and the large Balmer decrement (H_alpha/H_beta ~ 8) indicate significant amount of reddening is taking place in our line of sight in the host galaxy of the AGN; however, the X-ray spectrum is not absorbed by cold neutral gas intrinsic to the source. We discuss different explanations for this discrepancy between the reddening and the X-ray absorption, and suggest that the most likely solution is a dusty warm absorber. We show that dust can exist in the lower-ionised phase of the warm absorber, which causes the observed reddening of the optical-UV emission, whereas the X-rays remain unabsorbed due to lack of cold neutral gas in the ionised warm absorber. Furthermore, we have investigated the uncertainties in the construction of the Spectral Energy Distribution (SED) of this object due to obscuration of the nuclear source and the effects this has on the photoionisation modelling of the warm absorber. We show how the assumed SEDs influence the thermal stability of each phase and whether or not the two absorber phases in ESO 113-G010 can co-exist in pressure equilibrium.Comment: 11 pages, 5 figures, accepted for publication in Astronomy and Astrophysic

Role of Self-Stigma in Pathways from HIV-Related Stigma to Quality of Life among People Living with HIV

Funding Information: This study was supported by Viiv Healthcare, Gilead, and Aidsfonds (research Grant Number AF-P.42601). The funders had no role in decisions regarding the study design, data analysis, or publication. Acknowledgments We extend our gratitude to all PLHIV who completed the survey. We further thank the HIV specialist nurses and doctors at OLVG hospital for their effort in recruiting patients to complete the surveys.Peer reviewedPublisher PD

Optical Spectroscopy of Active Galactic Nuclei in SA57

The cosmological evolution of X-ray-selected and optically selected Active Galactic Nuclei (AGNs) show different behaviours interpreted in terms of two different populations. The difference is evident mainly for low luminosity AGNs (LLAGNs), many of which are lost by optical photometric surveys. We are conducting a spectroscopical study of a composite sample of AGN candidates selected in SA57 following different searching techniques, to identify low luminosity AGNs and break down the sample into different classes of objects. AGN candidates were obtained through optical variability and/or X-ray emission. Of special interest are the extended variable objects, which are expected to be galaxies hosting LLAGNs. Among the 26 classified objects a fair number (9) show typical AGN spectra. 10 objects show Narrow Emission Line Galaxy spectra, and in most of them (8/10) optical variability suggests the presence of LLAGNs.Comment: 7 pages, 8 figures, to appear in A&

A fatal pseudo-tumour: disseminated basidiobolomycosis

BACKGROUND: Basidiobolomycosis is a rare disease caused by the fungus Basidiobolus ranarum, member of the class Zygomycetes, order Entomophthorales, found worldwide. Usually basidiobolomycosis is a subcutaneous infection but rarely gastrointestinal manifestations have been described; 13 adults and 10 children and a few retroperitoneal or pulmonary cases. In gastrointestinal basidiobolomycosis the colon is most frequently involved, usually presenting with subacute mild abdominal pain. In contrast to children only very few described adult patients had hepatic masses. Definitive diagnosis requires culture, serological testing can be helpful. The fungal morphology and the Splendore-Hoeppli phenomenon are characteristic histological features. There are no prominent risk factors. Usually surgery and prolonged antifungal therapy are required. CASE PRESENTATION: A 61 year old man presented with progressive left abdominal pain and constipation since a few months. Colonoscopy showed an obstructing tumour in the descending colon, and a hemicolectomy was performed. Histology showed inflammation, possibly caused by a fungal or parasitic infection, without definite identification of an organism. A few weeks postoperatively a CT scan made because of abdominal discomfort, revealed a livermass (6 cm). Treatment with metronidazole, directed against an amoebic liver abscess, was unsuccessful. He developed a marked eosinophilia (27.7%). A liver biopsy was performed and the patient was referred to a university hospital. A repeated CT scan showed a livermass of 9 cm diameter. Review of colon and liver biopsy samples showed extensive necrosis and histiocytes, multinucleated giant cells and numerous eosinophils. Grocott stained sections contained unusually large hyphae surrounded by strongly eosinophilic material in haematoxylin and eosin stained sections (Splendore-Hoeppli phenomenon). A presumptive diagnosis of Basidiobolus spp. infection was made and treated with amphotericin B (Itraconazol contra-indicated because of renal insufficiency). A few days later the patient died of a septic shock. After autopsy Basidiobolus ranarum was cultured from liver, gallbladder and colon. CONCLUSION: Our patient died of gastrointestinal basidiobolomycosis with an obstructing colon tumour and a large hepatic mass. This was a rare presentation of basidiobolomycosis and the second fatal case described worldwide

USP15 deubiquitinase safeguards hematopoiesis and genome integrity in hematopoietic stem cells and leukemia cells

Altering ubiquitination by disruption of individual deubiquitinating enzymes (DUBs) has proven to affect hematopoietic stem cell (HSC) maintenance. However, comprehensive knowledge of DUB function during hematopoiesis in vivo is lacking. To accomplish this goal, we systematically inactivated DUBs in mouse hematopoietic progenitors using in vivo small hairpin RNAs (shRNAs) screens. We found that multiple DUBs may be individually required for hematopoiesis and that the ubiquitin-specific protease 15 (USP15) is particularly important for the maintenance of murine hematopoietic stem and progenitor cells in vitro and in vivo. Consistently, Usp15 knockout mice exhibited a reduced HSC pool. The defect was intrinsic to HSCs, as demonstrated by competitive repopulation assays. Importantly, USP15 is highly expressed in normal human hematopoietic cells and leukemias, and USP15 depletion in murine early progenitors and myeloid leukemia cells impaired in vitro expansion and increased genotoxic stress. Our study underscores the importance of DUBs in preserving normal hematopoiesis and uncovers USP15 as a critical DUB in safeguarding genome integrity in HSC and in leukemia cells

Dolutegravir/Lamivudine Is Noninferior to Continuing Dolutegravir- and Non-Dolutegravir-Based Triple-Drug Antiretroviral Therapy in Virologically Suppressed People With Human Immunodeficiency Virus:DUALING Prospective Nationwide Matched Cohort Study

Background. Confirming the efficacy of dolutegravir/lamivudine in clinical practice solidifies recommendations on its use. Methods. Prospective cohort study (DUALING) in 24 human immunodeficiency virus (HIV) treatment centers in the Netherlands. HIV RNA–suppressed cases were on triple-drug antiretroviral regimens without prior virological failure or resistance and started dolutegravir/lamivudine. Cases were 1:2 matched to controls on triple-drug antiretroviral regimens by the use of dolutegravir-based regimens, age, sex, transmission route, CD4+ T-cell nadir, and HIV RNA zenith. The primary endpoint was the treatment failure rate in cases versus controls at 1 year by intention-to-treat and on-treatment analyses with 5% noninferiority margin. Results. The 2040 participants were 680 cases and 1380 controls. Treatment failure in the 390 dolutegravir-based cases versus controls occurred in 8.72% and 12.50% (difference: −3.78% [95% confidence interval {CI}, −7.49% to .08%]) by intention-to-treat and 1.39% and 0.80% (difference: 0.59% [95% CI, –.80% to 1.98%]) by on-treatment analyses. The treatment failure risk in 290 non-dolutegravir-based cases was also noninferior to controls. Antiretroviral regimen modifications unrelated to virological failure explained the higher treatment failure rate by intention-to-treat. A shorter time on triple-drug antiretroviral therapy and being of non-Western origin was associated with treatment failure. Treatment failure, defined as 2 consecutive HIV RNA &gt;50 copies/mL, occurred in 4 cases and 5 controls but without genotypic resistance detected. Viral blips occured comparable in cases and controls but cases gained more weight, especially when tenofovir-based regimens were discontinued. Conclusions. In routine care, dolutegravir/lamivudine was noninferior to continuing triple-drug antiretroviral regimens after 1 year, supporting the use of dolutegravir/lamivudine in clinical practice.</p

Dolutegravir/Lamivudine Is Noninferior to Continuing Dolutegravir- and Non-Dolutegravir-Based Triple-Drug Antiretroviral Therapy in Virologically Suppressed People With Human Immunodeficiency Virus:DUALING Prospective Nationwide Matched Cohort Study

Background. Confirming the efficacy of dolutegravir/lamivudine in clinical practice solidifies recommendations on its use. Methods. Prospective cohort study (DUALING) in 24 human immunodeficiency virus (HIV) treatment centers in the Netherlands. HIV RNA–suppressed cases were on triple-drug antiretroviral regimens without prior virological failure or resistance and started dolutegravir/lamivudine. Cases were 1:2 matched to controls on triple-drug antiretroviral regimens by the use of dolutegravir-based regimens, age, sex, transmission route, CD4+ T-cell nadir, and HIV RNA zenith. The primary endpoint was the treatment failure rate in cases versus controls at 1 year by intention-to-treat and on-treatment analyses with 5% noninferiority margin. Results. The 2040 participants were 680 cases and 1380 controls. Treatment failure in the 390 dolutegravir-based cases versus controls occurred in 8.72% and 12.50% (difference: −3.78% [95% confidence interval {CI}, −7.49% to .08%]) by intention-to-treat and 1.39% and 0.80% (difference: 0.59% [95% CI, –.80% to 1.98%]) by on-treatment analyses. The treatment failure risk in 290 non-dolutegravir-based cases was also noninferior to controls. Antiretroviral regimen modifications unrelated to virological failure explained the higher treatment failure rate by intention-to-treat. A shorter time on triple-drug antiretroviral therapy and being of non-Western origin was associated with treatment failure. Treatment failure, defined as 2 consecutive HIV RNA &gt;50 copies/mL, occurred in 4 cases and 5 controls but without genotypic resistance detected. Viral blips occured comparable in cases and controls but cases gained more weight, especially when tenofovir-based regimens were discontinued. Conclusions. In routine care, dolutegravir/lamivudine was noninferior to continuing triple-drug antiretroviral regimens after 1 year, supporting the use of dolutegravir/lamivudine in clinical practice.</p