Urinary Tubular Injury Biomarkers Are Associated With ESRD and Death in the REGARDS Study.

IntroductionUrinary neutrophil gelatinase-associated lipocalin (uNGAL) and urinary kidney injury molecule-1 (uKIM-1) are established markers of subclinical acute kidney injury. In persons with reduced estimated glomerular filtration rate (eGFR) and albuminuria who are at high risk for end-stage renal disease (ESRD) and death, the associations of these urinary markers with incident ESRD or death is an area of active investigation.MethodsAmong 1472 black and white participants from the REasons for Geographic and Racial Differences in Stroke (REGARDS) study with eGFR ≤60 ml/min per 1.73 m2 (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] cystatin, 2012) and albumin-to-creatinine ratio (ACR) ≥30 mg/g, we evaluated the associations of baseline uNGAL and uKIM-1 with progression to ESRD and all-cause death. Cox models were sequentially adjusted for urinary creatinine, traditional risk factors, C-reactive protein, ACR, and eGFR.ResultsThere were 257 ESRD events and 819 deaths over a median follow-up of 5.7 and 6.5 years, respectively. In demographic adjusted models, higher levels of uNGAL were associated with increased risk of ESRD and death, but these associations were attenuated in fully adjusted models including baseline eGFR for both ESRD (hazard ratio [HR] = 1.06 per doubling, 95% confidence interval [CI] 0.98-1.14) and death (HR = 1.04, 95% CI = 1.00-1.08). Higher levels of uKIM-1 were associated with increased risk of ESRD and death in demographic-adjusted models, and although attenuated in fully adjusted models, remained statistically significant for both ESRD (HR = 1.24 per doubling, 95% CI = 1.08-1.42) and death (HR = 1.10, 95% CI =1.03-1.19).ConclusionIn this cohort of high-risk patients with baseline eGFR ≤60 ml/min per 1.73 m2 and albuminuria, renal tubular injury is associated with higher mortality and progression to ESRD. Further studies are necessary to investigate the mechanism underlying this increased risk

Ambient Particulate Matter Air Pollution and Venous Thromboembolism in the Women’s Health Initiative Hormone Therapy Trials

BackgroundThe putative effects of postmenopausal hormone therapy on the association between particulate matter (PM) air pollution and venous thromboembolism (VTE) have not been assessed in a randomized trial of hormone therapy, despite its widespread use among postmenopausal women.ObjectiveIn this study, we examined whether hormone therapy modifies the association of PM with VTE risk.MethodsPostmenopausal women 50–79 years of age (n = 26,450) who did not have a history of VTE and who were not taking anticoagulants were enrolled in the Women’s Health Initiative Hormone Therapy trials at 40 geographically diverse U.S. clinical centers. The women were randomized to treatment with estrogen versus placebo (E trial) or to estrogen plus progestin versus placebo (E + P trial). We used age-stratified Cox proportional hazard models to examine the association between time to incident, centrally adjudicated VTE, and daily mean PM concentrations spatially interpolated at geocoded addresses of the participants and averaged over 1, 7, 30, and 365 days.ResultsDuring the follow-up period (mean, 7.7 years), 508 participants (2.0%) had VTEs at a rate of 2.6 events per 1,000 person-years. Unadjusted and covariate-adjusted VTE risk was not associated with concentrations of PM 0.05) regardless of PM averaging period, either before or after combining data from both trials [e.g., combined trial-adjusted hazard ratios (95% confidence intervals) per 10 μg/m3 increase in annual mean PM2.5 and PM10, were 0.93 (0.54–1.60) and 1.05 (0.72–1.53), respectively]. Findings were insensitive to alternative exposure metrics, outcome definitions, time scales, analytic methods, and censoring dates.ConclusionsIn contrast to prior research, our findings provide little evidence of an association between short-term or long-term PM exposure and VTE, or clinically important modification by randomized exposure to exogenous estrogens among postmenopausal women

Natriuretic peptides and integrated risk assessment for cardiovascular disease. an individual-participant-data meta-analysis

BACKGROUND: Guidelines for primary prevention of cardiovascular diseases focus on prediction of coronary heart disease and stroke. We assessed whether or not measurement of N-terminal-pro-B-type natriuretic peptide (NT-proBNP) concentration could enable a more integrated approach than at present by predicting heart failure and enhancing coronary heart disease and stroke risk assessment. METHODS: In this individual-participant-data meta-analysis, we generated and harmonised individual-participant data from relevant prospective studies via both de-novo NT-proBNP concentration measurement of stored samples and collection of data from studies identified through a systematic search of the literature (PubMed, Scientific Citation Index Expanded, and Embase) for articles published up to Sept 4, 2014, using search terms related to natriuretic peptide family members and the primary outcomes, with no language restrictions. We calculated risk ratios and measures of risk discrimination and reclassification across predicted 10 year risk categories (ie, <5%, 5% to <7·5%, and ≥7·5%), adding assessment of NT-proBNP concentration to that of conventional risk factors (ie, age, sex, smoking status, systolic blood pressure, history of diabetes, and total and HDL cholesterol concentrations). Primary outcomes were the combination of coronary heart disease and stroke, and the combination of coronary heart disease, stroke, and heart failure. FINDINGS: We recorded 5500 coronary heart disease, 4002 stroke, and 2212 heart failure outcomes among 95 617 participants without a history of cardiovascular disease in 40 prospective studies. Risk ratios (for a comparison of the top third vs bottom third of NT-proBNP concentrations, adjusted for conventional risk factors) were 1·76 (95% CI 1·56-1·98) for the combination of coronary heart disease and stroke and 2·00 (1·77-2·26) for the combination of coronary heart disease, stroke, and heart failure. Addition of information about NT-proBNP concentration to a model containing conventional risk factors was associated with a C-index increase of 0·012 (0·010-0·014) and a net reclassification improvement of 0·027 (0·019-0·036) for the combination of coronary heart disease and stroke and a C-index increase of 0·019 (0·016-0·022) and a net reclassification improvement of 0·028 (0·019-0·038) for the combination of coronary heart disease, stroke, and heart failure. INTERPRETATION: In people without baseline cardiovascular disease, NT-proBNP concentration assessment strongly predicted first-onset heart failure and augmented coronary heart disease and stroke prediction, suggesting that NT-proBNP concentration assessment could be used to integrate heart failure into cardiovascular disease primary prevention

The medical student

The Medical Student was published from 1888-1921 by the students of Boston University School of Medicine

Explorations, Vol. 5, No. 1

Articles include: Cover: What Have We Done with Tomorrow? by Leslie C. Hyde, UMCES Extension Agent for Knox-Lincoln Counties. Editorial Reflections, Carole J. Bombard UMCES: an overview Conversation with the Director: Assistant Vice-President Judith Bailey Reaching Out for Teen Awareness, by Theresa M. Ferrari Profile of a Harbormaster, by Carole J. Bombard Minding Maine’s Business, by Mary S. Bowie Family Resource Management: Learning to ease the burden, by Olive Dubord and Doris Cushman Breaking Free and Taking Control: Helen Sawyer’s Story, by Doris Manley Partnership in Conservation: The Josephine Newman Sanctuary, by Nancy Coverstone The Mount Desert Island Health Promotion Project, by Ron Beard Dynamics of Weed Control in Agriculture, by Leigh Morrow From Generation to Generation: An Extension Homemaker Family, by Nadine B. Reimer ICLAD: The Institute for Community Leadership and Development, by Jim Killacky and Deb Burwell Exploding the Cinderella Syndrome: Strengthening Stepfamilies, by Wendy Pollock Integrated Pest Management: Bringing it all together, by Glen Koehler and Jim Dill Addressing the Issues, by Patricia M. Pierson Anti-Bruise: What’s It All About? Maine Potato Harvest Anti-Bruise Program, by Neal D. Hallee H.O.P.E. Addresses Teenage Pregnancy, by Jane M. Kelly Saving Money and the Environment, by Vaughn H. Holyoke Reservoir Tillage in Nonirrigated Potato Production, by Leigh Morrow Managing Pesticide Drift, by James D. Dwyer, Leigh S. Morrow and James F. Dill The St. George River Project — what have we done with tomorrow? Putting Research to Work, by Stephen Belyea The Best Maine Blue: Fresh Pack Blueberries, by Tom DeGomez Maine’s Green Sea Urchin, by Benjamin A. Baxter Interfaces and Cooperation: Wildlife and Fisheries Sampler, by Catherine A. Elliott Extension Responds to the Salmonella Scare, by Nellie Hedstrom and Mahmoud El-Begearm

Association of kidney function with inflammatory and procoagulant markers in a diverse cohort: A cross-sectional analysis from the Multi-Ethnic Study of Atherosclerosis (MESA)

Background: Prior studies using creatinine-based estimated glomerular filtration rate (eGFR) have found limited associations between kidney function and markers of inflammation. Using eGFR and cystatin C, a novel marker of kidney function, the authors investigated the association of kidney function with multiple biomarkers in a diverse cohort. Methods: The Multi-Ethnic Study of Atherosclerosis consists of 6,814 participants of white, African-American, Hispanic, and Chinese descent, enrolled from 2000-2002 from six U.S. communities. Measurements at the enrollment visit included serum creatinine, cystatin C, and six inflammatory and procoagulant biomarkers. Creatinine-based eGFR was estimated using the fourvariable Modification of Diet in Renal Disease equation, and chronic kidney disease was defined by an eGFR less than 60 mL/min/1.73 m2. Results: Adjusted partial correlations between cystatin C and all biomarkers were statistically significant: C-reactive protein (r = 0.08), interleukin-6 (r = 0.16), tumor necrosis factor-a soluble receptor 1 (TNF-aR1; r = 0.75), intercellular adhesion molecule-1 (r = 0.21), fibrinogen (r = 0.14), and factor VIII (r = 0.11; two-sided p less than 0.01 for all). In participants without chronic kidney disease, higher creatinine-based eGFR was associated only with higher TNF-aR1 levels. Conclusion: In a cohort characterized by ethnic diversity, cystatin C was directly associated with multiple procoagulant and inflammatory markers. Creatinine-based eGFR had similar associations with these biomarkers among subjects with chronic kidney disease.This research was supported by contracts N01-HC-95159 through N01-HC-95169 from the National Heart, Lung, and Blood Institute (NHLBI)

C-reactive protein, interleukin-6, and prostate cancer risk in men aged 65 years and older.

Inflammation is believed to play a role in prostate cancer (PCa) etiology, but it is unclear whether inflammatory markers C-reactive protein (CRP) and interleukin-6 (IL-6) associate with PCa risk in older men. Using Cox regression, we assessed the relationship between baseline concentrations of CRP and IL-6 and the subsequent PCa risk in the Cardiovascular Health Study, a population-based cohort study of mostly European American men of ages >64 years (n = 2,234; mean follow-up = 8.7 years; 215 incident PCa cases). We also tested associations between CRP and IL-6 tagSNPs and PCa risk, focusing on SNPs that are known to associate with circulating CRP and/or IL-6. Neither CRP nor IL-6 blood concentrations was associated with PCa risk. The C allele of IL-6 SNP rs1800795 (-174), a known functional variant, was associated with increased risk in a dominant model (HR = 1.44; 95% CI = 1.03-2.01; p = 0.03), but was not statistically significant after accounting for multiple tests (permutation p = 0.21). Our results suggest that circulating CRP and IL-6 do not influence PCa risk. SNPs at the CRP locus are not associated with PCa risk in this cohort, while the association between rs1800795 and PCa risk warrants further investigation

Heparin Dose Intensity and Organ Support-Free Days in Patients Hospitalized for COVID-19.

BACKGROUND Clinical trials suggest that therapeutic-dose heparin may prevent critical illness and vascular complications due to COVID-19, but knowledge gaps exist regarding the efficacy of therapeutic heparin including its comparative effect relative to intermediate-dose anticoagulation. OBJECTIVES The authors performed 2 complementary secondary analyses of a completed randomized clinical trial: 1) a prespecified per-protocol analysis; and 2) an exploratory dose-based analysis to compare the effect of therapeutic-dose heparin with low- and intermediate-dose heparin. METHODS Patients who received initial anticoagulation dosed consistently with randomization were included. The primary outcome was organ support-free days (OSFDs), a combination of in-hospital death and days free of organ support through day 21. RESULTS Among 2,860 participants, 1,761 (92.8%) noncritically ill and 857 (89.1%) critically ill patients were treated per-protocol. Among noncritically ill per-protocol patients, the posterior probability that therapeutic-dose heparin improved OSFDs as compared with usual care was 99.3% (median adjusted OR: 1.36; 95% credible interval [CrI]: 1.07-1.74). Therapeutic heparin had a high posterior probability of efficacy relative to both low- (94.6%; adjusted OR: 1.26; 95% CrI: 0.95-1.64) and intermediate- (99.8%; adjusted OR: 1.80; 95% CrI: 1.22-2.62) dose thromboprophylaxis. Among critically ill per-protocol patients, the posterior probability that therapeutic heparin improved outcomes was low. CONCLUSIONS Among noncritically ill patients hospitalized for COVID-19 who were randomized to and initially received therapeutic-dose anticoagulation, heparin, compared with usual care, was associated with improved OSFDs, a combination of in-hospital death and days free of organ support. Therapeutic heparin appeared superior to both low- and intermediate-dose thromboprophylaxis

Gene-Centric Meta-Analysis of Lipid Traits in African, East Asian and Hispanic Populations

Meta-analyses of European populations has successfully identified genetic variants in over 100 loci associated with lipid levels, but our knowledge in other ethnicities remains limited. To address this, we performed dense genotyping of ∼2,000 candidate genes in 7,657 African Americans, 1,315 Hispanics and 841 East Asians, using the IBC array, a custom ∼50,000 SNP genotyping array. Meta-analyses confirmed 16 lipid loci previously established in European populations at genome-wide significance level, and found multiple independent association signals within these lipid loci. Initial discovery and in silico follow-up in 7,000 additional African American samples, confirmed two novel loci: rs5030359 within ICAM1 is associated with total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) $(p = 8.8×10^{−7} and p = 1.5×10^{−6}$ respectively) and a nonsense mutation rs3211938 within CD36 is associated with high-density lipoprotein cholesterol (HDL-C) levels $(p = 13.5×10^{−12})$. The rs3211938-G allele, which is nearly absent in European and Asian populations, has been previously found to be associated with CD36 deficiency and shows a signature of selection in Africans and African Americans. Finally, we have evaluated the effect of SNPs established in European populations on lipid levels in multi-ethnic populations and show that most known lipid association signals span across ethnicities. However, differences between populations, especially differences in allele frequency, can be leveraged to identify novel signals, as shown by the discovery of ICAM1 and CD36 in the current report