Discovering Novel Biochemical and Genetic Markers for Coronary Heart Disease in Qatari Individuals: The Initiative Qatar Cardiovascular Biorepository.

BACKGROUND: We aimed to describe the creation and challenge of a DNA and plasma biorepository (Qatar Cardiovascular Biorepository) with linkage to the electronic health record of cardiovascular risk factors to facilitate discovery of novel genetic and proteomic biomarkers for coronary heart disease in Qatari individuals. METHODS: A prospective case-control study was conducted between October 2013 and February 2018. CHD was defined as a history of an acute coronary syndrome (myocardial infarction [MI]/unstable angina) or coronary revascularization. Controls were identified from blood donors who had no history of coronary heart diesase. After informed consent, blood samples were obtained for DNA and plasma. Demographic, laboratory, and clinical variables were derived from the electronic medical record, and information regarding history of cardiovascular diseases and risk factors was collected from surveys. Challenges in establishing the biorepository were noted, and processes to promote use of the biorepository by Qatari investigators were put in place. RESULTS: During the study period, 2671 individuals were approached; of them, 2087 participants were recruited (1029 patients and 1058 controls). Relevant risk factors were ascertained from the electronic health record and surveys. The mean age was 49 ± 16 years, with 61% males. Challenges included setting up the infrastructure for qatar cardiovascular biorepository, developing an informed consent document in Arabic/English, and meeting target recruitment goals. The prevalence of diabetes mellitus, hypertension, dyslipidemia, and smoking was 41%, 44.5%, 40%, and 19%, respectively. History of myocardial infarction, percutaneous coronary intervention, and coronary artery bypass surgery was 55%, 68%, and 17%, respectively, among patients. CONCLUSIONS: This study addresses the challenges in setting up qatar cardiovascular biorepository, the first cardiovascular genomics biorepository in the Arab Middle Eastern region. QCBio is a unique resource for identifying genetic susceptibility variants and novel circulating markers for coronary heart disease in Qatari adults and enables individualized assessment of risk for coronary heart disease.

Greening the Operating Room: Results of a Scalable Initiative to Reduce Waste and Recover Supply Costs.

Operating rooms generate 42% of a hospital's revenue and 30% of hospital waste. Supply costs are 56% of a total operating room (OR) budget. US academic medical centers use 2 million pounds ($15 million) of recoverable medical supplies annually. Forming a multidisciplinary leadership team, we analyzed sources of waste focusing on our Department of Neurosurgery. We developed an 8-wk pilot project to recycle "blue wrap," the number 5 plastic polypropylene material that is ubiquitously used in ORs across the country to wrap instrument pans and implant trays for sterilization. Blue wrap can be baled and sold to recyclers where the material is pelletized and transformed into plastic products. During the 39 d of the pilot, we collected 1247 pounds of blue wrap (32 lbs collected daily). The cost of the pilot was $14 987 that includes a new baler ($11 200) and 5 transport carts ($3697). The revenue received from baled blue wrap was 8 cents per pound. Cost avoidance yielded $31 680.00 in savings. Implementation of this pilot across our main hospital would yield $5000 in revenue annually and $174 240 in cost avoidance. This project can be replicated at other centers and not only reduces the environmental footprint, but also helps generate additional revenue by recycling a necessary packing material that would otherwise require payment for disposal.

Whole exome sequencing implicates an INO80D mutation in a syndrome of aortic hypoplasia, premature atherosclerosis, and arterial stiffness.

BACKGROUND: Massively parallel, high-throughput sequencing technology is helping to generate new insights into the genetic basis of human diseases. We used whole exome sequencing to identify the mutation underlying a syndrome affecting 2 siblings with aortic hypoplasia, calcific atherosclerosis, systolic hypertension, and premature cataract. METHODS AND RESULTS: Exonic regions were captured and sequenced using a next-generation sequencing platform to generate 100 bases paired-end reads. A computational genomic data analysis pipeline was used to perform quality control, align reads to a reference genome, and identify genetic variants; findings were confirmed using a different exome analyses pipeline. The 2 siblings were homozygous for a rare missense mutation (Ser818Cys) in INO80D, a subunit of the human INO80 chromatin remodeling complex. Homozygosity mapping and Sanger sequencing confirmed that the mutation is located in one of the runs of homozygosity on chromosome 2. INO80D encodes a key subunit of the human IN080 complex, a multiprotein complex involved in DNA binding, chromatin modification, organization of chromosome structure, and ATP-dependent nucleosome sliding. By introducing a new disulphide-bond in the protein product and also disrupting the composition of low-complexity regions, the Ser818Cys mutation may affect INO80D function, protein-protein interactions, and chromatin remodeling. CONCLUSIONS: Our findings suggest a link between the Ser818Cys mutation in INO80D, a subunit of the human INO80 chromatin remodeling complex, and accelerated arterial aging.

An electronic medical record-linked biorepository to identify novel biomarkers for atherosclerotic cardiovascular disease.

BACKGROUND: Atherosclerotic vascular disease (AVD), a leading cause of morbidity and mortality, is increasing in prevalence in the developing world. We describe an approach to establish a biorepository linked to medical records with the eventual goal of facilitating discovery of biomarkers for AVD. METHODS: The Vascular Disease Biorepository at Mayo Clinic was established to archive DNA, plasma, and serum from patients with suspected AVD. AVD phenotypes, relevant risk factors and comorbid conditions were ascertained by electronic medical record (EMR)-based electronic algorithms that included diagnosis and procedure codes, laboratory data and text searches to ascertain medication use. RESULTS: Up to December 2012, 8800 patients referred for vascular ultrasound examination and non-invasive lower extremity arterial evaluation were approached, of whom 5268 consented. The mean age of the initial 2182 patients recruited was 70.4 ± 11.2 years, 62.6% were men and 97.6% were whites. The prevalences of AVD phenotypes were: carotid artery stenosis 48%, abdominal aortic aneurysm 21% and peripheral arterial disease 38%. Positive predictive values for electronic phenotyping algorithms were>0.90 for cases (and>0.95 for controls) for each AVD phenotype, using manual review of the EMR as the gold standard. The prevalences of risk factors and comorbidities were as follows: hypertension 78%, diabetes 29%, dyslipidemia 73%, smoking 70%, coronary heart disease 37%, heart failure 12%, cerebrovascular disease 20% and chronic kidney disease 19%. CONCLUSIONS: Our study demonstrates the feasibility of establishing a biorepository of plasma, serum and DNA, with relatively rapid annotation of clinical variables using EMR-based algorithms.