Utility of B-type natriuretic peptide in predicting medium-term mortality in patients undergoing major non-cardiac surgery

We assessed the ability of pre-operative B-type natriuretic peptide (BNP) levels to predict medium-term mortality in patients undergoing major noncardiac surgery. During a median 654 days follow-up 33 patients from a total cohort of 204 patients (16%) died. The optimal cut-off in this cohort, determined using a receiver operating characteristic curve, was >35pg.mL-1. This was associated with a 3.47-fold increase in the hazard of death (p=0.001) and had a sensitivity of 70% and a specificity of 68% for this outcome. These findings extend recent work demonstrating that BNP levels obtained before major noncardiac surgery can be used to predict peri-operative morbidity, and indicate that they also forecast medium-term mortality.This work was supported by a grant from TENOVUS Scotland. The Health Services Research Unit is core-funded by the Chief Scientists Office of the Scottish Executive Health Department.Peer reviewedAuthor versio

Pre-diagnosis plasma immune markers and risk of non-Hodgkin lymphoma in two prospective cohort studies

Inflammation and B-cell hyperactivation have been associated with non-Hodgkin lymphoma development. This prospective analysis aimed to further elucidate pre-diagnosis plasma immune marker profiles associated with non-Hodgkin lymphoma risk. We identified 598 incident lymphoma cases and 601 matched controls in Nurses\u27 Health Study and Health Professionals Follow-up Study participants with archived pre-diagnosis plasma samples and measured 13 immune marker levels with multiplexed immunoassays. Using multivariable logistic regression we calculated odds ratios and 95% confidence intervals per standard deviation unit increase in biomarker concentration for risk of non-Hodgkin lymphoma and major histologic subtype, stratifying additional models by years ( \u3c 5, 5 to \u3c 10, \u3e /=10) after blood draw. Soluble interleukin-2 receptor-alpha, CXC chemokine ligand 13, soluble CD30, and soluble tumor necrosis factor receptor-2 were individually positively associated, and B-cell activating factor of the tumor necrosis factor family inversely associated, with all non-Hodgkin lymphoma and one or more subtypes. The biomarker combinations associated independently with lymphoma varied somewhat by subtype and years after blood draw. Of note, the unexpected inverse association between B-cell activating factor and chronic lymphocytic leukemia/small lymphocytic lymphoma risk (odds ratio: 95% confidence interval: 0.51, 0.43-0.62) persisted more than 10 years after blood draw (odds ratio: 0.70; 95% confidence interval: 0.52-0.93). In conclusion, immune activation precedes non-Hodgkin lymphoma diagnosis by several years. Decreased B-cell activating factor levels may denote nascent chronic lymphocytic leukemia many years pre-diagnosis

Deconvolving the contributions of cell-type heterogeneity on cortical gene expression

Complexity of cell-type composition has created much skepticism surrounding the interpretation of bulk tissue transcriptomic studies. Recent studies have shown that deconvolution algorithms can be applied to computationally estimate cell-type proportions from gene expression data of bulk blood samples, but their performance when applied to brain tissue is unclear. Here, we have generated an immunohistochemistry (IHC) dataset for five major cell-types from brain tissue of 70 individuals, who also have bulk cortical gene expression data. With the IHC data as the benchmark, this resource enables quantitative assessment of deconvolution algorithms for brain tissue. We apply existing deconvolution algorithms to brain tissue by using marker sets derived from human brain single cell and cell-sorted RNA-seq data. We show that these algorithms can indeed produce informative estimates of constituent cell-type proportions. In fact, neuronal subpopulations can also be estimated from bulk brain tissue samples. Further, we show that including the cell-type proportion estimates as confounding factors is important for reducing false associations between Alzheimer\u27s disease phenotypes and gene expression. Lastly, we demonstrate that using more accurate marker sets can substantially improve statistical power in detecting cell-type specific expression quantitative trait loci (eQTLs)

The challenge of measuring intra-individual change in fatigue during cancer treatment

Evaluate how well three different patient-reported outcomes (PROs) measure individual change

Higher soluble CD14 levels are associated with lower visuospatial memory performance in youth with HIV.

OBJECTIVE: HIV-associated neurocognitive disorders persist despite early antiretroviral therapy (ART) and optimal viral suppression. We examined the relationship between immunopathogenesis driven by various pathways of immune activation and discrete neurocognitive performance domains in youth with HIV (YWH). DESIGN: Observational cross-sectional study. METHODS: YWH, ages 20-28 years, enrolled in Adolescent Medicine Trials Network 071/101 were assessed for biomarkers of macrophage, lymphocyte activation, and vascular inflammation using ELISA/multiplex assays. Standardized neurocognitive tests were performed, and demographically adjusted z-scores were combined to form indices of attention, motor, executive function, verbal, and visuospatial memory. Cross-sectional analysis of the relationship between 18 plasma inflammatory biomarkers and each neurocognitive domain was performed. Linear regression models were fit for each combination of log-transformed biomarker value and neurocognitive domain score, and were adjusted for demographics, socioeconomic status, substance use, depression, CD4 T-cell count, HIV viral load, and ART status. RESULTS: Study included 128 YWH [mean age 23.8 (SD 1.7) years, 86% men, 68% African American]. Verbal and visuospatial memory domains were most significantly impaired in the cohort (z=-1.59 and -1.0, respectively). Higher sCD14 was associated with impaired visuospatial memory, which remained robust after adjusting for other biomarkers, demographics, and HIV-associated covariates. Among biomarkers of vascular inflammation, sICAM-1 was negatively associated with verbal memory and attention, whereas sVCAM-1 was positively associated with executive function and visuospatial memory. Specific neurocognitive domains were not associated with sCD163, LPS, or CCL2 levels. CONCLUSION: Impaired visuospatial memory in YWH is associated with immune activation, as reflected by higher sCD14

Genome analysis of the necrotrophic fungal pathogens Sclerotinia sclerotiorum and Botrytis cinerea

Sclerotinia sclerotiorum and Botrytis cinerea are closely related necrotrophic plant pathogenic fungi notable for their wide host ranges and environmental persistence. These attributes have made these species models for understanding the complexity of necrotrophic, broad host-range pathogenicity. Despite their similarities, the two species differ in mating behaviour and the ability to produce asexual spores. We have sequenced the genomes of one strain of S. sclerotiorum and two strains of B. cinerea. The comparative analysis of these genomes relative to one another and to other sequenced fungal genomes is provided here. Their 38–39 Mb genomes include 11,860–14,270 predicted genes, which share 83% amino acid identity on average between the two species. We have mapped the S. sclerotiorum assembly to 16 chromosomes and found large-scale co-linearity with the B. cinerea genomes. Seven percent of the S. sclerotiorum genome comprises transposable elements compared t

‘Some anti-malarials are too strong for your body, they will harm you.’ Socio-cultural factors influencing pregnant women’s adherence to anti-malarial treatment in rural Gambia

Background Despite declining prevalence of malaria in The Gambia, non-adherence to anti-malarial treatment still remains a challenge to control efforts. There is limited evidence on the socio-cultural factors that influence adherence to anti-malarial treatment in pregnancy. This study explored perceptions of malaria in pregnancy and their influence on adherence to anti-malarial treatment in a rural area of The Gambia. Methods An exploratory ethnographic study was conducted ancillary to a cluster-randomized trial on scheduled screening and treatment of malaria in pregnancy at village level in the Upper River Region of The Gambia from June to August 2014. Qualitative data were collected through interviewing and participant observation. Analysis was concurrent to data collection and carried out using NVivo 10. Results Although women had good bio-medical knowledge of malaria in pregnancy, adherence to anti-malarial treatment was generally perceived to be low. Pregnant women were perceived to discontinue the provided anti-malarial treatment after one or 2 days mainly due to non-recognition of symptoms, perceived ineffectiveness of the anti-malarial treatment, the perceived risks of medication and advice received from mothers-in-law. Conclusion Improving women’s knowledge of malaria in pregnancy is not sufficient to assure adherence to anti-malarial treatment. Addressing structural barriers such as unclear health workers’ messages about medication dosage, illness recognition, side effects of the medication and the integration of relatives, especially the mothers-in-law, in community-based programmes are additionally required