Genetics of Coronary Artery Disease: Discovery, Biology and Clinical Translation !

Genetics

Coronary artery disease is the leading global cause of mortality. Long recognized to be heritable, recent advances have started to unravel the genetic architecture of the disease. Common variant association studies have linked approximately 60 genetic loci to coronary risk. Large-scale gene sequencing efforts and functional studies have facilitated a better understanding of causal risk factors, elucidated underlying biology and informed the development of new therapeutics. Moving forwards, genetic testing could enable precision medicine approaches by identifying subgroups of patients at increased risk of coronary artery disease or those with a specific driving pathophysiology in whom a therapeutic or preventive approach would be most useful.

• Coronary artery disease is a heritable disorder that remains the leading cause of global mortality despite advances in treatment and prevention strategies. Human genetics studies have started to unravel the genetic underpinnings of this disorder.
• Gene discovery efforts have rapidly transitioned from family-based studies (for example, those that led to the discovery of familial hypercholesterolaemia) to large cohorts that facilitate both common and rare variant association studies.
• Common variant association studies have confirmed ∼60 genetic loci with a robust association with coronary disease, the majority of which are of modest effect size and in non-coding regions. Rare variant association studies have linked inactivating mutations in at least nine genes with risk of coronary artery disease.
• Human genetics and large-scale biobanks can facilitate drug development for coronary artery disease by highlighting causal biology and helping to understand the phenotypic consequences of lifelong deficiency of a given protein.
• Genomic medicine may provide patients and their health care providers with genetic data that will aid in coronary artery disease prevention and treatment.
• Genome editing to introduce mutations that are protective against coronary artery disease into the population could prove curative with a one-time injection, although substantial additional work is needed to confirm efficacy and safety, and to address the underlying ethics.

Observational epidemiology and translational research efforts have led to significant progress in improving the understanding of the pathophysiology underlying coronary artery disease (CAD). Prevention and treatment strategies developed on the basis of this knowledge led to a >50% decrease in age-adjusted CAD mortality rate in the United States between 1980 and 2000. However, despite these advances, CAD remains the leading global cause of mortality. Current predictions estimate that more than 900,000 individuals in the United States will suffer a myocardial infarction (heart attack) or die of CAD this year.

This review outlines research efforts to understand the genetic drivers of CAD, the role of human genetics in catalysing CAD drug discovery efforts and the promises and challenges of integrating genetic information into routine clinical practice.

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Sepsis And The Hematology Laboratory

An affordable, widely available test can impact today`s biggest healthcare challenge.

Sepsis, the inflammatory response to infection, is quickly becoming one of the biggest healthcare problems worldwide. No matter the perspective one takes, the numbers are staggering. Currently the number of diagnosed cases per year in the United States is at least 750,000; some estimates surpass one million. Worldwide mortality estimates are as high as 20 percent, and thus we are dealing with one of the biggest drivers of mortality in modern medicine. Sepsis kills nearly as many people as heart attack, HIV, and breast cancer combined.

Viewed from the perspective of health economics, the average in-hospital cost per case is approximately $20,000 dollars, and yearly estimates of sepsis-related expenses in the U.S. alone exceed $20 billion.

Read more: Sepsis And The Hematology Laboratory

Source: MedicalLaboratoryObserver

Serum Albumin Levels Associated with Mortality in Hemodialysis Patients

Serum albumin is commonly used as a proxy for nutritional status, as well as a marker of inflammation and a low serum albumin concentration is not only indicative of protein energy wasting in dialysis patients, but it is also a powerful predictor of the mortality risk in this population.

Several clinical conditions are associated with low serum albumin levels in dialysis patients, including infectious and inflammatory diseases, fluid overload, inadequate dialysis, severe co-morbidity, and taste change. Therefore, regular monitoring of serum albumin levels is useful for predicting outcomes in dialysis patients.

Read more: Enlarged Prostate: Molecular Mechanism Clue May Explain Link To Inflammation

The Hitachi 7600–210 modular clinical biochemistry analyzer (Photo courtesy of Hitachi).

Source: labmedica

Current Approaches For The Detection Of Acute Kidney Injury

Acute kidney injury is a recognized complication in hospitalized patients and is associated with a high morbidity and high mortality. This brief article aims to summarize the need for early detection of acute kidney injury and the current approach within NHS England to identify such patients.

Background

Acute kidney injury (AKI) is a recognized complication in hospitalized patients. A report in 2009 from National Confidential Enquiry into Patient Outcome and Death (NCEPOD) suggested that AKI was frequently undetected in hospital patients thus contributing to patient morbidity and mortality.

Clinical guidelines for recognition and treatment for acute kidney injury were published by NICE (the National Institute for Health and Care Excellence) in 2013 and reported an associated mortality with AKI of more than 25–30%. This guideline also recognized the prevalence of AKI in the primary care population in patients with or without acute illness.

NICE also recognized the impact of AKI on healthcare resources, with costs (excluding those in the community) of £434–620 million per year, more than that associated with breast, lung and skin cancer combined.

Read more: Current Approaches For The Detection Of Acute Kidney Injury

Table 1. Common causes of acute kidney injury.

Source: cli-online

Current Approaches for the Detection of Acute Kidney Injury

Acute kidney injury (AKI) is a recognized complication in hospitalized patients. A report in 2009 from National Confidential Enquiry into Patient Outcome and Death (NCEPOD) suggested that AKI was frequently undetected in hospital patients thus contributing to patient morbidity and mortality. Clinical guidelines for recognition and treatment for acute kidney injury were published by NICE (the National Institute for Health and Care Excellence) in 2013 and reported an associated mortality with AKI of more than 25–30%. This guideline also recognized the prevalence of AKI in the primary care population in patients with or without acute illness. NICE also recognized the impact of AKI on healthcare resources, with costs (excluding those in the community) of £434–620 million per year, more than that associated with breast, lung and skin cancer combined

AKI is characterized by an acute loss of the kidney’s excretory capacity leading to accumulation of waste products such as urea and creatinine, and decreased urine output. It is associated with rapid decline in glomerular filtration rate and increases in potassium, phosphate and hydrogen ions. It has varied causes and may be secondary to a non-renal event, thus may be common in hospitalized patients and critically ill patients. It may go undetected in primary care as it can occur without any symptoms. There are associations between co-morbidities, current medications, acute illness and AKI resulting in the high morbidity associated with the condition and the impact on healthcare resources.

Read more: Current Approaches for the Detection of Acute Kidney Injury

Source: cli-online

Tools for Lung Cancer Research

Recent advances in lung cancer research suggest a personalized approach to diagnostics and therapeutics to reduce mortality

Due to its high rate of mortality, lung cancer is a prominent area of research for scientists. Lung cancer is a complex disease with many subtypes resulting from factors such as family history, lifestyle and occupation-with each subtype requiring different treatment regimens. Thus, developing therapeutics for this disease requires vast research efforts.

The specific subtypes of the cancer must be paired to successful treatments, which can then be matched to individual patients. The American Type Culture Collection (ATCC) has responded to this initiative for personalized medicine by creating new drug screening and diagnostic test development tools, such as tumor cell panels based on genetic alteration, primary cells, gene-edited isogenic cell lines and cell line derivatives.

"Over the years, we have expanded our portfolio into the most diverse and unique collection of cancer cells to include thousands of human and animal cancer cell lines representing the diversity of the disease," said Fang Tian, PhD, lead scientist at ATCC. "Our growing collection of lung cancer cell lines is now just shy of 100 lines.

Read more: Tools for Lung Cancer Research

Source: laboratory-manager.advanceweb