Vogeljustesen2922

uncommon cause of severe hyponatremia.

The performance of the galactomannan enzyme immunoassay (GM-EIA) is impaired in patients receiving mould-active antifungal therapy. The impact of mould-active antifungal therapy on Aspergillus PCR testing needs to be determined.

To determine the influence of anti-mould prophylaxis (AMP) on the performance of PCR blood testing to aid the diagnosis of proven/probable invasive aspergillosis (IA).

As part of the systematic review and meta-analysis of 22 cohort studies investigating Aspergillus PCR blood testing in 2912 patients at risk of IA, subgroup analysis was performed to determine the impact of AMP on the accuracy of Aspergillus PCR. The incidence of IA was calculated in patients receiving and not receiving AMP. The impact of two different positivity thresholds (requiring either a single PCR positive test result or ≥2 consecutive PCR positive test results) on accuracy was evaluated. Meta-analytical pooling of sensitivity and specificity was performed by logistic mixed-model regression.

In total, 166robable IA using the EORTC/MSGERC definitions.

Rifapentine exposure is associated with bactericidal activity against Mycobacterium tuberculosis, but high interindividual variation in plasma concentrations is encountered.

To investigate a genomic association with interindividual variation of rifapentine exposure, SNPs of six human genes involving rifamycin metabolism (AADAC, CES2), drug transport (SLCO1B1, SLCO1B3) and gene regulation (HNF4A, PXR) were evaluated.

We characterized these genes in 173 adult participants in treatment trials of the Tuberculosis Trials Consortium. Participants were stratified by self-identified race (black or non-black), and rifapentine AUC from 0 to 24 h (AUC0-24) was adjusted by analysis of covariance for SNPs, rifapentine dose, sex, food and HIV coinfection. This study was registered at ClinicalTrials.gov under identifier NCT01043575.

The effect on rifapentine least squares mean AUC0-24 in black participants overall decreased by -10.2% for AADAC rs1803155 G versus A allele (Wald test P = 0.03; false discovery rate, 0. exposure. Further pharmacogenomic study is needed to characterize the association of the AADAC rs1803155 with inadequate rifapentine exposure in different patient groups.Multiple sclerosis is an autoimmune disease of the CNS in which both genetic and environmental factors are involved. Genome-wide association studies revealed more than 200 risk loci, most of which harbour genes primarily expressed in immune cells. However, whether genetic differences are translated into cell-specific gene expression profiles and to what extent these are altered in patients with multiple sclerosis are still open questions in the field. To assess cell type-specific gene expression in a large cohort of patients with multiple sclerosis, we sequenced the whole transcriptome of fluorescence-activated cell sorted T cells (CD4+ and CD8+) and CD14+ monocytes from treatment-naive patients with multiple sclerosis (n = 106) and healthy subjects (n = 22). We identified 479 differentially expressed genes in CD4+ T cells, 435 in monocytes, and 54 in CD8+ T cells. Pixantrone Importantly, in CD4+ T cells, we discovered upregulated transcripts from the NAE1 gene, a critical subunit of the NEDD8 activating enzyme, which activates the neddylation pathway, a post-translational modification analogous to ubiquitination. Finally, we demonstrated that inhibition of NEDD8 activating enzyme using the specific inhibitor pevonedistat (MLN4924) significantly ameliorated disease severity in murine experimental autoimmune encephalomyelitis. Our findings provide novel insights into multiple sclerosis-associated gene regulation unravelling neddylation as a crucial pathway in multiple sclerosis pathogenesis with implications for the development of tailored disease-modifying agents.

Diminished mental health is associated with increased morbidity and mortality and may contribute to loss of independence and motivation in patients receiving dialysis and their caregivers. Increased understanding of the patient perspective on triggers, impacts and strategies for managing mental health may inform ways to address mental health conditions in this population.

A secondary thematic analysis was undertaken using data from the Standardized Outcomes in Nephrology (SONG)-Hemodialysis and SONG-Peritoneal Dialysis projects. We extracted and analysed data on the perceived causes, meaning, impact and management of mental health in patients receiving dialysis from 26 focus groups (in six countries), multinational Delphi surveys and consensus workshops.

A total of 644 patients and caregivers participated. We identified five themes bound to dialysis (forced into isolation, enslaved to a machine, stress of relentless planning and grieving the loss of a normal life), underrecognized and ignored (missed by burden, which can impair motivation for self-management. Increased attention to monitoring and management of mental health in this population is needed.

Serum anti-dsDNA and anti-nucleosome IgGs have been proposed as signatures for SLE and LN in limited numbers of patients. We sought to show higher sensitivity and specificity of the same antibodies with the IgG2 isotype and included IgG2 antibodies vs specific intracellular antigens in the analysis.

A total of 1052 SLE patients with (n = 479) and without (n = 573) LN, recruited at different times from the beginning of symptoms, were included in the study. Patients with primary APS (PAPS, n = 24), RA (RA, n = 24) and UCTD (UCTD, n = 96) were analysed for comparison. Anti-nucleosome (dsDNA, Histone2A, Histone3), anti-intracellular antigens (ENO1), anti-annexin A1 and anti-C1q IgG2 were determined by non-commercialtechniques.

The presence in the serum of the IgG2 panel was highly discriminatory for SLE/LN vs healthy subjects. Serum levels of anti-dsDNA and anti-C1q IgG2 were more sensitive than those of IgGs (Farr radioimmunoassay/commercial assays) in identifying SLE patients at low-medium increments. Of more importance, serum positivity for anti-ENO1 and anti-H2A IgG2 discriminated between LN and SLE (ROC T0-12 months), and high levels at T0-1 month were detected in 63% and 67%, respectively, of LN, vs 3% and 3%, respectively, of SLE patients; serum positivity for each of these was correlated with high SLEDAI values. Minor differences existed between LN/SLE and the other rheumatologic conditions.

Nephritogenic IgG2 antibodies represent a specific signature of SLE/LN, with a few overlaps with other rheumatologic conditions. High levels of anti-ENO1 and anti-H2A IgG2 correlated with SLE activity indexes and were discriminatory between SLE patients limited to the renal complication and other SLE patients.

The Zeus study was registered at https//clinicaltrials.gov, NCT02403115.

The Zeus study was registered at https//clinicaltrials.gov, NCT02403115.