Rationale and design of the Kidney Precision Medicine Project

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The Effect of Left Ventricular Assist Device Therapy on Cardiac Biomarkers: Implications for the Identification of Myocardial Recovery

Purpose of Review

Left ventricular assist device (LVAD) therapy serves as mainstay therapy for bridge to transplantation and destination therapy. Evidence is now mounting on the role of LVAD therapy as bridge to recovery. In the current review, we will summarize the data on biomarkers of myocardial recovery following LVAD implantation.

Recent Findings

Myocardial recovery can occur spontaneously, following pharmacological intervention and in the setting of mechanical circulatory support such as LVAD. Several biomarkers such as B-type natriuretic peptide (BNP), N-terminal pro B-type natriuretic peptide (NT-proBNP), ST2, etc. have been identified and are being used to guide medical therapy in heart failure (HF) patients. However, recent data raised concern that those biomarkers may not be helpful in managing heart failure patients in general, and as such questioned their use in the advanced heart failure population. At this point, the use of biomarker to identify patients with myocardial recovery during LVAD support has not been established, and LVAD explantation remains a decision driven by echocardiographic and hemodynamics improvement.

Summary

HF biomarkers in monitoring myocardial and neurohormonal activation response to mechanical unloading and medical therapy could be valuable. However, at this time, there is inadequate evidence to select a single or a set of HF biomarkers to reliably identify patients bridged to recovery for LVAD explantation.

     

Determinants of turnover among low wage earners in long term care: the role of manager-employee relationships

The demand for Long-Term Care (LTC) is steadily increasing as Baby Boomers age and enter retirement. High turnover rates among employees in LTC creates challenges for supervisors and administrators, and can negatively impact quality of care. This study examines manager-subordinate relationship quality using Leader-Member Exchange Theory (LMX) as an antecedent to turnover among low-wage earners in the LTC environment. Survey data measuring LMX, job satisfaction, and demographic information was collected at time 1, and turnover data was collected 18 months later at time 2. The results reveal that all four LMX dimensions were rated significantly different among subordinates who left versus those who stayed, however, only the LMX dimension of supervisor loyalty was a significant predictor of turnover among low wage earners. Our study adds a more nuanced view of the reasons low-wage employees turnover, and presents implications for clinical managers and LTC organizations more broadly.     

Anticoagulation in patients with atrial fibrillation,thrombocytopenia and hematological malignancy

Journal of Thrombosis and Thrombolysis - Managing anticoagulation in hematological malignancy patients with atrial fibrillation and thrombocytopenia is a clinical challenge with limited data. We...     

Infective endocarditis in diabetic and non-diabetic patients

We compared clinical, microbiological, and prognostic characteristics of infective endocarditis in patients with and without diabetes mellitus. In 1987--1996, 213 patients with definite or possible infective endocarditis were included, of which 39 (18%) had diabetes mellitus. Diabetic patients were older than non-diabetic (median age of 71 vs 65 y, respectively; p =0.04), had more aortic valve and less mitral valve involvement (71% vs 27%, and 21% vs 62%; p = 0.004). There was no significant difference in the frequency of Staphylococcus aureus involvement between the 2 groups (21% in diabetic vs 20% in non-diabetic group; p = ns). On multivariate analysis diabetes mellitus was not found to be an independent factor for mortality. Unlike other infections diabetes mellitus does not significantly affect clinical and microbiological features, and outcome of infective endocarditis.     

Effect of serum from leukapheresed mice on myelocytes, promyelocytes and colony-forming cells.

Leukapheresis of neutrophil granulocytes in mice increased the myelopoietic activity of their serum. Leukapheresed mouse serum (LMS) caused a threefold increase in the in vitro stathmokinetic index of myeloid precursors. Five to ten minutes of incubation were sufficient to change the colony-forming capacity of mouse bone marrow cells as expressed by the increase in the ratio of granuloid to erythroid cells in spleen colonies. The in vitro stathmokinetic index assay also showed that there are diurnal variations in levels of granulopoietic activity in normal mouse sera. However, at any time of the day, LMS had higher granulopoietic activity.     

Discovery of novel non-synonymous SNP variants in 988 candidate genes from 6 centenarians by target capture and next-generation sequencing

Despite evidence of a substantial genetic component, the genetic factors that underlie longevity in humans remain to be identified. Previous genome-wide linkage and association studies have not found strong evidence for the contribution of common variants besides the APOE gene, suggesting the role of rare variants in human longevity. To discover rare variants that might contribute to longevity, we selected 988 candidate genes and performed a pilot study to identify novel non-synonymous variants in 6 Ashkenazi Jewish centenarians older than 105. Our candidate genes act in pathways implicated in aging and longevity, including neurodegeneration, cognitive function, lipid metabolism, DNA repair, and genome maintenance. By implementing custom-designed Agilent SureSelect target capture and next-generation sequencing, we discovered a total of 89 novel non-synonymous SNPs (nsSNPs) and validated 51 nsSNPs by iPLEX MassArray assays. Genotyping analysis of these novel SNPs in 410 Ashkenazi Jewish controls and 390 centenarians showed significant enrichment (5.3 fold, p = 0.02) of the p.Y318C variant in PMS2 and significant depletion (7.5 fold, p = 0.04) of the p.V465A variant in GABRR3 in centenarians compared to controls. Our study presents the potential of targeted next-generation sequencing for discovery of rare but functional genetic variation which may lead to exceptional longevity in humans.