Category Archives: Genetic medicine

News Release

Wednesday, December 8, 2021

Researchers have linked a rare genetic mutation found mostly in Black Americans and other people of African descent to an earlier onset of heart failure and a higher risk of hospitalization. The findings suggest that earlier screening for the mutation could lead to faster treatment and improved outcomes for heart failure in this vulnerable group, the researchers said. The results of the study, which was largely supported by the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health, appear in the Journal of the American College of Cardiology: Heart Failure.

This is the most comprehensive evaluation of the association between this mutation and measures of cardiac structure, heart function, and heart failure risk in an exclusively Black population, said lead study author Ambarish Pandey, M.D., assistant professor of internal medicine in the Division of Cardiology at University of Texas Southwestern Medical Center in Dallas. The results also highlight the importance of early genetic screening in patients at higher risk for carrying the mutation.

Heart failure is a chronic, debilitating condition that develops when the heart cant pump enough blood to meet the bodys needs. Despite the name, it does not mean that the heart has stopped beating. Common symptoms include shortness of breath during daily activities or trouble breathing when lying down. The condition affects about 6.5 million people in the United States alone. Black Americans are at higher risk for the condition than any other racial/ethnic group in the U.S., and they experience worse outcomes.

The genetic variant studied in the current research had long ago been linked to a higher risk of heart failure in people of African ancestry. Known as TTR V142I, the gene can cause a condition called transthyretin amyloid cardiomyopathy, which is potentially fatal because protein builds up inside the heart. However, little was known about the impact of the mutation on important clinical-related factors such as heart structure, heart function, hospitalization rates, and blood biomarkers.

To learn more, the researchers studied TTR V142I in a group of middle-aged participants from the 20-year-long Jackson Heart Study, the largest and longest investigation of cardiovascular disease in Black Americans. Of the 2,960 participants selected from the study, about 119 (4%) had the genetic mutation, but none had heart failure at the start. The researchers followed the participants for about 12 years between 2005 and 2016.

During the study period, the researchers observed 258 heart failure events. They found that patients who carried the genetic mutation were at significantly higher risk of developing heart failure, compared to those without the mutation. These patients also developed heart failure nearly four years earlier and had a higher number of heart failure hospitalizations. Researchers said they found no significant difference in death rates between the two groups during this study period.

During follow-up studies, however, they observed significant increases in blood levels of troponin, a protein complex that is an important marker of heart damage, among carriers of the genetic mutation. They did not see any significant associations between the genetic mutation and changes in heart structure and function as evaluated by echocardiographic and cardiac MRI assessments.

What that means is that the gene is causing heart damage slowly over time, said Amanda C. Coniglio, M.D., the lead author of the study and a physician with Duke University School of Medicine in Durham, North Carolina. The changes are subtle but significant.

The researchers noted that more studies will be needed to continue assessing participants heart structure and function and to see, long-term, if increased hospitalization risk translates into higher risk of death.

Identification of genetic susceptibility to amyloid cardiomyopathy is an important advance related to heart failure, especially given its disproportionate effect on older and multiethnic populations, said Patrice Desvigne-Nickens, M.D., a medical officer in the Heart Failure and Arrhythmia Branch in NHLBIs Division of Cardiovascular Sciences.

Adolfo Correa, M.D., Ph.D., study co-author and former director of the Jackson Heart Study, agreed. About half of Black American men and women living in the United States today have some form of cardiovascular disease, but the root causes are poorly understood, he said. This study brings us a step closer to better understanding this particular form of gene-related heart failure, as well as the life-saving importance of early screening.The Jackson Heart Study is supported and conducted in collaboration with Jackson State University (HHSN268201800013I), Tougaloo College (HHSN268201800014I), the Mississippi State Department of Health (HHSN268201800015I/HHSN26800001) and the University of Mississippi Medical Center (HHSN268201800010I, HHSN268201800011I, and HHSN268201800012I) contracts from the NHLBI and the National Institute on Minority Health and Health Disparities. Additional NIH funding support includes the National Institute of Diabetes and Digestive and Kidney Diseases grant 1K08DK099415- 01A1; National Institute of General Medical Sciences grants P20GM104357 and 5U54GM115428.

About the National Heart, Lung, and Blood Institute (NHLBI): NHLBI is the global leader in conducting and supporting research in heart, lung, and blood diseases and sleep disorders that advances scientific knowledge, improves public health, and saves lives. For more information, visit http://www.nhlbi.nih.gov.

About the National Institutes of Health (NIH):NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

NIHTurning Discovery Into Health

Transthyretin V142I Genetic Variant and Cardiac Remodeling, Injury, and Heart Failure Risk in Black Adults. JACC-Heart Failure.DOI: 10.1016/j.jchf.2021.09.006

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Rare gene mutation in some Black Americans may allow earlier screening of heart failure - National Institutes of Health

Introduction

Despite race being a socio-political system of categorization without a biologic basis, race has historically and continues to play a role in medical teaching and clinical decision making within health care. Race permeates clinical decision making and treatment in multiple ways, including: (1) through providers attitudes and implicit biases, (2) disease stereotyping and clinical nomenclature, and (3) clinical algorithms, tools, and treatment guidelines. While some diseases have higher prevalence among individuals with certain genetic ancestry, genetic ancestry is poorly correlated with commonly used social racial categories. The use of race to inform clinical diagnoses and decision making may reinforce disproven notions of race as a biological construct and contribute to ongoing racial disparities in health and health care. This brief provides an overview of the role of race in clinical care and discusses the implications for health and health care disparities and efforts to advance health equity.

Despite there being no biologic basis to race, the medical and scientific community have used race to explain differences in disease prevalence and outcomes. The Western concept of race arose as a system of hierarchical human categorization to support European colonialization, oppression, and discrimination of non-European groups. Within U.S. medical curricula, the concept of race led to theories of biological inferiority of people of color and White supremacy, which fueled an array of atrocities in medicine including forced sterilization efforts targeting Black and Native American women, the use of Henrietta Lacks cells for scientific research without consent or acknowledgement, and the infamous Tuskegee Syphilis study, among others. Although research has since disproven the existence of universal biologic differences by race, some recent scientific studies continue to suggest that genetic differences between racial groups may explain differences in health outcomes. For example, an article published in 2020 originally suggested that unknown or unmeasured genetic or biological factors may be contributing to increased severity of COVID-19 illness among Black people, although the article was later revised to clarify that the difference is most likely explained by societal factors. Recent research further suggests that measures of demographic characteristics and socioeconomic position may be more effective than genetic characteristics in explaining disparities in cardiovascular disease between Black and White adults.

There have been growing calls against using race as a factor to explain health differences without acknowledging the role of racism. Contemporary science has demonstrated that race is a social category with no basis in biology. Race is a poor proxy for genetic ancestry and large genetic studies have demonstrated more variation within defined racial groups (intra-racially) than there are between different racial groups (inter-racially). Within the medical and scientific community, there have been longstanding critiques of using racial classifications in diagnosis and treatment of disease. Recently, there have been calls for research studies and guidance in the medical community to name and examine the role of racism versus race as a key driver of health inequities to avoid perpetuating disproven understandings of biologic differences by race.

Although race is not tied to biologic differences, understanding differences in health and health care by race and ethnicity remains important for identifying and addressing disparities in health and health care that stem from racism and social and economic inequities. Complete and accurate race and ethnicity data is key for identifying disparities and taking action to address them. However, there are longstanding gaps and limitations in racial and ethnic data within health care. In addition to deficiencies in survey and administrative data, many institutions report gaps in electronic health record (EHR) data on race, with substantial misclassification of self-reported race and preferred language. The largest discrepancies between EHR demographic data and self-reported data are among individuals who identify as Hispanic.

A significant and longstanding body of research suggests that provider and institutional bias and discrimination are drivers of racial disparities in health, contributing to racial differences in diagnosis, prognosis, and treatment decisions. Prior work suggests that providers historically were more likely to perceive individual patient factors rather than provider or health system influences as causes for health disparities. For example, studies have found that providers view Black patients as less cooperative with medical treatment and that providers associate Hispanic patients with noncompliance and risky behavior. A 2015 systematic review of published studies showed that most health care providers appear to have implicit bias in terms of positive attitudes towards White people and negative attitudes towards people of color. While some studies have found no link between bias and provider treatment behaviors, others have demonstrated that provider bias correlates with poorer patient-provider interactions and is associated with disparities in pain management and empathy. Providers who endorse false beliefs about biological differences by race report lower pain for Black patients compared to White patients, which has been linked to systematic undertreatment for pain of Black patients. Similarly, compared to White patients in emergency departments, Hispanic and Asian patients are less likely to receive pain assessments and appropriate pain medication.

Research also shows that patients report being treated unfairly because of their race/ethnicity while accessing health care. For example, a 2020 KFF/the Undefeated survey of adults found that Black and Hispanic adults are more likely than White adults to report they were personally treated unfairly because of their race and ethnicity while getting health care in the past year. Black adults also are more likely than White adults to report negative experiences with health care providers, including feeling a provider did not believe they were telling the truth, being refused a test or treatment they thought they needed, and being refused pain medication. In addition, Black and Hispanic adults are more likely than their White counterparts to say it is difficult to find a doctor who shares their background and experiences and one who treats them with dignity and respect.

Some medical training approaches and materials use imprecise labels conflating race and ancestry, portray diseases through racial stereotypes, and rely on racial heuristics (i.e., mental shortcuts or associations) for teaching clinical diagnosis. Preclinical lectures and clinical vignettes for teaching use nonspecific labels (e.g., Black instead of Nigerian/Haitian and Asian instead of Chinese/Vietnamese/Pakistani) and may misuse race as a surrogate for genetic ancestry. In some cases, they inappropriately use race as a proxy for differences in socioeconomic status, health behaviors (such as diet), or other factors that may influence access to health care or risk of disease. In addition, lecture materials commonly present racial differences in disease burden without historical or social context, which may contribute to students connecting diseases with certain racial groups and ascribing differences to genetic predisposition. For example, preclinical lecturers often teach that recurrent lung infections in White individuals are indicative of cystic fibrosis, which may result in missed diagnoses of cystic fibrosis among Black patients. The hereditary condition glucose-6-phosphate dehydrogenase (G6PD) deficiency, which can cause severe anemia, affects individuals of all racial and ethnic backgrounds, with highest prevalence in Africa, the Middle East, and certain parts of the Mediterranean and Asia. However, lecturers and board materials teach students to have higher clinical suspicion for diagnosis of this deficiency in Black patients. In nearly all medical learning resources, Lyme disease is depicted predominantly on White skin and is often diagnosed much later when the disease has progressed to arthritic stages among Black patients. Other examples of connecting race to disease exist in medical textbooks. For example, Black skin is more commonly used to depict sexually transmitted diseases. A recently recalled textbook for nursing students published in 2017 suggested that there were racial differences in how patients experience and respond to pain. The text described Black patients as reporting higher pain intensity than other cultures, Hispanic patients as having wide expression of pain (some are stoic and some are expressive), Asian patients as valuing stoicism as a response to pain, and Native American patients as being less expressive both verbally and nonverbally. Beyond teaching materials, medical board examinations often test students based on race-based guidelines and heuristics.

Some disease names use racial or geographic terms that link diseases to certain groups or communities. For example, congenital dermal melanocytosis was formerly referred to as Mongolian spot. Similarly, Down syndrome was first described as Mongolism by a 19th century British physician who believed that patients with the genetic disorder resembled individuals of Mongolian descent. As another example, vancomycin infusion reaction was formerly called Red Man syndrome, evoking racist connotations against Indigenous American people. Clinical nomenclature has shifted towards more descriptive language, although in some cases, disease naming is tied to place of discovery. Disease names incorporating geography may still perpetuate racist-xenophobic sentiment. In 2015, the World Health Organization noted associating disease names with geography may result in backlash towards members of particular ethnic communities. This experience was seen in the recent use of the label China virus for the COVID-19 virus, which has been associated with an increase in public anti-Asian sentiment and Asian hate crimes, as well as an increase in depressive symptoms among individuals identifying with multiple Asian subgroups. Moreover, a recent KFF survey of Asian community health center patients found that one in three felt more discrimination based on their racial/ethnic background since the COVID-19 pandemic began in the U.S. and 15% said they had been accused of spreading or causing COVID-19.

While some diseases have higher prevalence among individuals with certain genetic ancestry, the practice of using race within clinical calculators and screening metrics may contribute to health disparities. Today, clinical calculators across multiple specialties assign differential risk for certain diseases or conditions based on race. Prior work has identified a range of examples of clinical calculators that use race (Appendix Table 1). One of the most well-known examples of this practice is within nephrology, where separate measures of kidney function (i.e., estimated glomerular filtration rates, eGFRs) are applied to Black patients compared to non-Black patients. However, similar examples are seen across medicine. For example, a common calculator used to predict success of vaginal birth after Cesarian (VBAC) section had a correction factor for both Black and Hispanic race that decreases the success of VBAC for Black and Hispanic patients by 67% and 68% respectively. This tool may bias providers into disproportionately counseling these patients towards undergoing a Cesarian section. Similarly, pulmonary function tests have a race correction factor, East Asian race is considered a major risk factor for neonatal jaundice, and a different Body Mass Index threshold is used to recommend diabetes testing among asymptomatic Asian and Pacific Islander patients. Given that race is an extremely inconsistent proxy for genetic ancestry, this use of race within clinical calculators may lead to both undertreatment and overtreatment of racialized individuals, and delays in diagnosis and clinical care.

Research shows that some clinical tools may be less effective or misused for certain populations. For example, pulse oximeters have low accuracy in measuring oxygen saturation in darker skin and are three times as likely to miss low oxygen levels in Black patients compared to White patients. Such discrepancies may contribute to delayed intervention and increased mortality for Black patients with COVID-19. In pediatrics, findings suggest that jaundice measurement tools (i.e., bilirubinometer for measurement of transcutaneous bilirubin) have varied reliability based on skin color, with underestimates of risk in lighter skin and overestimates in darker skin tone. Overestimates of bilirubin using transcutaneous measurements may result in unnecessary follow-up blood work (an invasive process for infants), increases in follow-up visits and commute to clinics, and increased infant caregiver distress. In lower resource settings where serum bilirubin measurement is unavailable and transcutaneous bilirubinometry continues to be the primary method for infant monitoring, underestimates of risk may result in delayed intervention for the life-threatening condition neonatal kernicterus, while overestimates of risk for hyperbilirubinemia may result in unnecessary prolonged hospital stays and treatment. In dermatology, the dearth of images depicting lesions on dark skin in medical and dermatologic textbooks and lack of representation of providers with darker skin in the specialty may result in reduced clinician ability to identify life-threatening dermatological presentation on people of color (e.g., sepsis, cellulitis, or severe drug reactions to medications). Skin cancer, while less common in Black and Hispanic patients, is often diagnosed later with subsequently lower survival rates. Fitzpatrick skin type (FS) is the most commonly used skin type classification system in dermatology. It was originally designed to describe the likelihood of skin to burn from UV light exposure but is misused by many providers to describe skin color as a proxy for race.

Preventing against racial bias will be important as use of artificial intelligence and algorithms to guide clinical decision-making continue to expand. The health care system is increasingly using artificial intelligence and algorithms to guide health decisions. Research has shown that these algorithms may have racial bias because the underlying data on which they are trained may be biased and/or may not reflect a diverse population. For example, one study found that an algorithm designed to identify patients with complex health needs resulted in Black patients being assigned the same level of risk as White patients despite being sicker. This unintended bias occurred because of underlying racial bias in how the algorithm was designed, implemented, and interpretedthe algorithm used health care costs to predict health care needs, but Black patients have lower health care costs in part because they face greater barriers to accessing health care. Other examples have found that skewed dermatological datasets result in less accurate models and decreased ability to diagnose skin conditions among darker skin tones. However, research also suggests that carefully designed algorithms can mitigate bias and help to reduce disparities in care.

Race also factors into some medication prescribing decisions, but the use of race is often based on limited evidence from small studies and may result in inappropriate dosing and treatment. In 2005, the U.S. Food and Drug Administrative approved the drug BiDil as a race-specific drug to treat heart failure among African Americans. It was subsequently critiqued for misguided marketing due to using race as a proxy for genotype, which was not evaluated in the study from which conclusions were drawn, although it remains approved as a race-based drug today. There are additional examples of race-based prescribing guidelines. For example, hydrochlorothiazide is recommended as first line hypertension therapy for Black patients based on Joint National Committee (JNC) Hypertension guidelines, as opposed to ACE inhibitor therapy for all other groups due to presumed inefficacy of these agents among Black patients. Eltrombopag, a drug used to treat thrombocytopenia, has a lower recommended starting dose for East Asian patients compared to all other patients. Similarly, the Food and Drug Administration recommends a lower starting dose for Crestor (a statin, used to lower lipid levels) for Asian patients based on a gene that confers metabolic variability, despite the understanding that this gene may be prevalent among any population. There has been ongoing discussion around race-based dosing and the utility of race-based genetic screening for drugs such as warfarin (commonly used for anticoagulation therapy) and abacavir for HIV treatment. Medical community viewpoints on race-based prescribing vary. For example, a study of American cardiologists found that many providers believe race-based drug labels in treatment of heart failure may help prescribe effective medications sooner, while others expressed concerns that considering race could potentially harm patients by resulting in some patients not receiving the drug.

The use of race in the emerging field of pharmacogenomics has come under increasing scrutiny. Pharmacogenomics explores the relationships between genes and drug effects and is viewed as a way to potentially personalize medical therapy. Pharmacogenomics research often uses race to guide decisions about genetic screening prior to using certain drugs to prevent against adverse drug events based on the assumption that certain racial categories may have high or low prevalence of certain genes. Proponents argue that race-based targeting in the field of pharmacogenetics is useful to propel personalized medicine for patient care at the individual level. However, critiques of race-specific therapies express concerns around attempting to address health disparities through commercial drug development versus examining upstream structural factors that may explain differences in treatment response. Moreover, as noted, genetic variation within certain racial/ethnic groups can exceed variation across racial/ethnic categories, suggesting limited utility of this approach and that it may run counter to personalized medicine by treating people based on groupings that have limited genetic association. Current work has limited representation from communities of color, resulting in less extrapolatable, premature recommendations for clinical screening for diverse communities. In addition, inequities across the continuum of drug development and clinical trial participation and evaluation may exacerbate existing disparities in medication access for communities of color, including decreased access to novel, high-cost medications and lower-cost generic therapies.

The use of race within clinical decision making and treatment may reinforce disproven concepts of racial biology and exacerbate health inequities. Race continues to permeate medical teaching and clinical decision making and treatment in multiple ways, including: (1) through providers attitudes and implicit biases, (2) disease stereotyping and nomenclature, and (3) clinical algorithms and treatment guidelines. Racial bias among providers may contribute to poorer quality of care and worse health outcomes. Racial stereotyping of disease and use of race in clinical algorithms and treatment guidelines may lead to errors in clinical diagnosis and management (overtreatment or undertreatment and other delays in clinical care), which may perpetuate and potentially worsen health disparities. Moreover, continued use of race as a biological concept limits examination and understanding of social drivers of health inequities, including racism, and contributes to ongoing racial bias and discrimination among providers.

There have been growing efforts within the medical community to re-evaluate and revise practices around the use of race within clinical care and efforts to move towards race-conscious (as opposed to race-based) medicine. In 2020, the American Medical Association (AMA) adopted new policies to recognize race as a social construct and, as part of these policies, encourages medical education programs to recognize the harmful effects of using race as a proxy for biology in medical education through curriculum changes that explain how racism results in health disparities. In September 2020, the House Ways and Means Committee announced a Request for Information around the misuse of race in clinical care. The Agency for Healthcare Research and Quality (AHRQ) similarly announced in March 2021 a Request for Information on the use of clinical algorithms that have the potential to introduce racial/ethnic bias into healthcare delivery. A subsequent Ways and Means final report released in October 2021 found that professional societies suggest more research (with evaluation of unintended consequences of removing race correctors) is needed before decisions can be made, as a growing number of institutions have removed race from clinical calculators. For example, in the past year-and-a-half, Mass General Brigham hospital, the University of Washington, Vanderbilt University, and NYC Health and Hospitals have all removed race corrections from kidney function estimates. The UC Davis School of Medicine also eliminated race-based reference ranges from renal function estimates, followed shortly by UCSFs release of a new approach to estimate kidney function without race. Moreover, both the American Society of Nephrology and National Kidney Foundation have outlined approaches to diagnose kidney disease without race. In November 2021, the New York City Department of Health launched a Coalition to End Racism in Clinical Algorithms, pledging to end race adjustment in at least one clinical algorithm and to create plans for evaluation of racial inequities and patient engagement. Additionally, some commonly used medical calculators have made use of race correction factors optional, while others have removed them entirely (see Appendix Table 1). In contrast, other institutions have held off on making changes to clinical calculators or guidelines, noting potential downstream implications for other aspects of clinical care and management.

Looking ahead, continued education of health care providers and students to eliminate beliefs of biologic differences by race, improving pedagogy around distinctions between race and genetic ancestry, and reducing racial bias and discrimination will be important, as will efforts to increase the diversity of our health care workforce. Moreover, continued careful evaluation of how race factors into clinical decision-making through clinical guidelines, tools, and algorithms will be important for mitigating biased decision making, particularly as the use of artificial intelligence and machine-driven algorithms to guide clinical decisions expand.

Michelle Tong is a fourth year medical student at the University of California, San Francisco, completing a health policy fellowship with the Kaiser Family Foundation. Samantha Artiga serves as Vice President and Director of the Racial Equity and Health Policy Program at KFF. The authors thank Dr. Louis H. Hart III and Dr. Monica Hahn for their expertise and subject matter review. Dr. Louis Hart is the Medical Director of Health Equity for Yale New Haven Health System and Assistant Professor of Pediatric Hospital Medicine at the Yale School of Medicine. Dr. Monica Hahn is the Co-Founder of the Institute for Healing and Justice in Medicine and Associate Clinical Professor at UCSF in the Department of Family and Community Medicine.

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Use of Race in Clinical Diagnosis and Decision Making: Overview and Implications - Kaiser Family Foundation

Carlos Fernndez-Hernando

Carlos Fernndez-Hernando, whose work combines cell biology, genetics, and mouse models to study lipid metabolism and cardiovascular related disorders, was recently appointed the Anthony N. Brady Professor of Comparative Medicine and Pathology.

He is also a member of the Vascular Biology & Therapeutics Program and the Yale Center for Molecular Metabolism.

After earning a bachelors degree in chemistry and his Ph.D. in biochemistry/molecular biology from Universidad Autnoma de Madrid in Spain, Fernndez-Hernando completed a postdoctoral fellowship at Hospital Ramn y Cajal, Spain. He then continued his postdoctoral training with Prof. William Sessa at Yale from 2005 to 2009. Then, after starting his laboratory in the Department of Medicine at New York University, he returned to Yale in 2013.

His research aims to identify and characterize novel mechanisms by which cholesterol and lipoprotein metabolism is regulated. Work from his group identified miRNA-33a/b, an intronic miRNA encoded within the intronic sequences of SREBP genes, the master transcriptional regulators that control lipid metabolism. In a number of relevant studies his group was able to demonstrate that miRNA-33a/b provides a critical link between the regulation of cholesterol and fatty acid biosynthesis by SREBP and cholesterol efflux, high-density lipoprotein (HDL) biogenesis and fatty acid oxidation pathways. Fernndez-Hernando group and colleagues found that pharmacological inhibition of miR-33 increases hepatic ABCA1 expression, circulating HDL-C and attenuates the progression of atherosclerosis. His group has also uncovered the first non-coding RNA (miRNA-148a) that regulates plasma low-density lipoprotein (LDL)-C levels via hepatic LDLR using a genome-wide miRNA screen. These findings correlate with recent reports that identified a genetic variation in the miR-148a locus associated with plasma LDL-C and triglycerides in humans. Together, these contributions have provided novel insights about the molecular mechanisms that regulate cellular lipid homeostasis and lipoprotein metabolism.

Fernndez-Hernando has authored or co-authored more than 150 research articles, many of them in prominent journals, including Science, Nature, Nature Medicine, Cell Metabolism, Journal of Clinical Investigation and Proceding of the National Academy of Sciences, among other publications. He has been the recipient of numerous awards for his contributions in the field of lipid metabolism and vascular biology including the Irvine Page Young Investigator Award (American Heart Association), Springer Award (North American Vascular Biology Association), David L. Williams Award (Kern Lipid Conference), Established Investigator Award (American Heart Association), Jeffrey M. Hoeg Atherosclerosis, Thrombosis & Vascular Biology Award in Basic Science and Clinical Research (American Heart Association), R35EIA from NHBLI and the Folkman Award in Vascular Biology (North American Vascular Biology Association).

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Fernndez-Hernando named Anthony N. Brady Professor of Comparative Medicine - Yale News

The consortium brings together genome-wide association data from 200 cohort studies across the globe, allowing research teams to closely investigate key genetic variation related to blood cholesterol levels in a lot of people at once. U.S. veterans participating in the Million Veteran Program were a major contributor to the increased diversity of the GLGC. In all, around 500 scientists who have collected and analyzed these data are credited as co-authors.

The researchers already knew they needed many, many participants in order to draw big conclusions about lipid levels. What they didnt know in advance was exactly how big the benefit would be of studying diverse samples.

Of three aspects of the research they examined, diversity made a big difference for two of them, and a smaller difference for the third. Willer said they identified approximately the same number of total genetic variation related to lipids (thousands of them), irrespective of the level of diversity.

However, for homing in on the functional gene, or for predicting high cholesterol levels, researchers report that diversity was critically important.

We find that increasing the diversity of the populations studied rather than simply increasing sample size more efficiently identifies the genetic variants that control cholesterol levels in our blood, Assimes said. Importantly, we can potentially level the playing field when it comes to predicting cholesterol levels if we introduce diversity into our study design, and the more diversity we introduce, the better.

LDL cholesterol is a warning bell for future cardiovascular events like heart attacks, so a high cholesterol level in an annual physical is likely to lead to a discussion about how to lower it.

If you could find out in advance that you were more susceptible to having high blood lipids, or high risk of heart attacks, then you could reduce your cholesterol before it even becomes a problem, Graham said.

SEE ALSO: Cholesterol-carrying protein found to help suppress immune response in pancreatic tumor microenvironment

We hope this study will one day allow physicians to better identify people at risk of high cholesterol and cardiovascular disease who may benefit from lifestyle changes or lipid-lowering medication earlier in life, she added.

This study also suggests that genetic studies of any diseases would likely benefit from studying people of diverse ancestries, researchers said.

We should work hard to ensure that genetics research benefits all people, and improving diversity of ancestries represented in research is an important step towards equality, Willer said.

Paper cited: The power of genetic diversity in genome-wide association studies of lipids, Nature. DOI: 10.1038/d41586-021-02998-2

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Making the case for more diversity in genetic research - Michigan Medicine

Content

Can genetic testing shed light on your risk for cardiovascular disease? A Baylor College of Medicine cardiologist will address this question and more at an upcoming Evenings with Genetics virtual seminar on Tuesday, Dec. 14, at 7 p.m.

During the hourlong webinar, Dr. Christie Ballantyne, professor of medicine and section chief of cardiology and cardiovascular research at Baylor, will lead a discussion on precision medicine and heart disease. He will cover topics like what genetic tests are available, who should consider genetic testing and how these tests are helpful in assessing risk for heart disease.

Cardiovascular disease, the most common cause of death for both men and women in the United States, has a very important genetic component, said Ballantyne, director of the Center for Cardiometabolic Disease Prevention at Baylor. If you have a family history, it is very helpful to know which tests you should get and also what you should do to reduce your risk from cardiovascular disease.

Evenings with Genetics is a regular speaker series hosted by Baylor College of Medicine and Texas Childrens Hospital that offers the most current information on care and research advances for many genetic conditions.

The program is free and open to the public, but registration is required. A Zoom link will be sent to all registered participants the day before the seminar. For more information, call 713-798-8407 or visit the event registration page.

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Evenings with Genetics addresses genetic testing and heart disease - Baylor College of Medicine News

Developers of individualized investigational antisense oligonucleotide (ASO) therapies for ultra-rare diseases received additional guidance from the US Food and Drug Administration (FDA). In two draft documents, the agency has provided new information for sponsor-investigators and for those overseeing manufacture of these so-called N of 1 therapies for people with severely debilitating or life-threatening genetic disease."Progress in individualized medicines provides hope to patients with severely debilitating or life-threatening genetic diseases, said acting FDA commissioner Janet Woodcock in a press release accompanying the new draft guidances. Advances in technology enable targeting a drug to an individual patient's genes. Single-subject clinical trialsalso called 'N of 1' trialsfocus on evaluating investigational drug products developed for an individual patient.Woodcock continued, This field is rapidly evolving, and antisense oligonucleotide drugs are the most advanced in this space. However, many N of 1 trials are carried out by academic investigators who may not have much experience interacting with the FDA. Earlier this year, the FDA took initial steps to provide draft guidance to investigators carrying out this critical work. Today, we are issuing additional draft guidance in this area. Once finalized, this guidance will detail important clinical and production considerations to support applications for these types of clinical trials and drug development programs.The newly released draft guidances complement a January 2021 draft guidance covering administrative and procedural considerations for ASO developers and an April document that focuses on nonclinical testing of the therapies. (RELATED: 'N of 1' therapies addressed in draft FDA guidance, Regulatory Focus 5 January 2021)Woodcock and Peter Marks, head of FDAs biologics center, addressed some of the ethical and practical issues that arise in regulating these hyper-specialized therapies in a 2019 New England Journal of Medicine editorial. On a larger scale, we need to consider how such truncated programs fit into the spectrum of drug development in general: what are the differences between treating one, ten, or thousands of patients? asked the regulators in the editorial.Guidance for clinical investigatorsThe draft guidance for clinical investigators covers a gamut of clinical considerations ranging from ethical and human subject considerations to recommendations for conducting diagnostic and genetic testing and determining dosing. The document also lays out suggested procedures for administration of the drug product and provides guidance on assessing both safety and clinical response to ASO therapy.In addition to obtaining informed consent for participants, sponsors should conduct genetic testing that ensures that the gene variant or variants intended to be the target of an ASO drug is the cause of the patients pathology, and that the variant is unique to that patient.Dosing considerations should build on experience with related ASO drug products; the starting dose should be expected to have a pharmacologic effect. These dose estimates may have to be calculated based on known interspecies differences; investigators should plan for a dose escalation strategy and monitor patients closely while cautiously increasing the dose. De-escalation in case of toxicity should be planned for.ASO administration should be conducted in an inpatient setting with special staffing and monitoring precautions taken when doses are administered intrathecally. The guidance specifies what routine safety assessments should be conducted, providing special considerations for ASOs that have phosphorothioate or mixed-phosphorothioate backbones, since these products can cause thrombocytopenia. This portion of the guidance also advises investigators to be on the lookout for such ASO-specific risks as off-target genetic effects, building on experience with other ASO products in the same chemical class and on bioinformatics analyses.Clinical response can be evaluated through a clearly defined program of clinical assessments that may include performance-based, clinician-reported, and patient- or caregiver-reported assessments. Biomarkers that are scientifically justified and relevant to the target disease may also be helpful in assessing response. In weighing whether to continue administering an ASO product, sponsors should weigh toxicity against any observed clinical benefits.CMC considerationsA second guidance document released on Tuesday lays out general considerations for chemistry, manufacturing and controls (CMC) in ASO drug development. These recommendations support first-in-human exposure for the individualized ASO drug products covered under this guidance and do not address regulatory considerations for continued, long-term administration of an individualized ASO drug product or other circumstances that fall outside of the N of 1 investigational sphere, according to the guidance.Although there are many aspects of the manufacturing process of an investigational ASO drug product that differ from traditional pharmaceutical products, FDA still expects that sponsor will provide enough CMC information in their investigational new drug (IND) application to ensure the proper identification, quality, purity, and strength of the investigational drug product. The draft guidance recommends a pre-IND meeting with FDA to talk through CMC plans for the ASO product.Another key regulatory consideration is that ASO drug products do not ordinarily move from phase 1 to 2 to 3 in their clinical development process. Accordingly, the manufacture of the first batch of an ASO drug product can confirm with the current good manufacturing practices (CGMP) expected at the phase 1 stage, but subsequent batches should comply with CGMP requirements for finished pharmaceuticals as laid out in 21 CFR 211.Taking these regulatory recommendations into account, the draft guidance on CMC for ASO drug products recommends that, when possible, the same batch of drug product used for the nonclinical studies be used for initial clinical investigations, to simplify quality assessments.It could also be the case that CMC information from other individualized ASO drug products could be incorporated by reference either to another IND or a drug master file, noted FDA in the draft guidance.As for other drug substances, sponsors of N of 1 ASO drug products should provide a description of the physical and chemical characteristics of the drug, including such ASO-specific information as the base moieties and backbone of the therapy. The submission should also include information about the general method for preparation, with a flow diagram and a clear description of process controls that ensure quality of the drug substance.In terms of characterization, the sequence determination should be included in the IND or provided as soon as possible in an amendment after providing a justification in the IND. Both ASO-related and nonrelated impurities should also be addressed in the characterization.The specification section of the IND should include the identity of the ASO drug substance achieved through a combination or two or more methods, such as sequencing and molecular weight determination; a strength assay; quantities of determined and unidentified impurities; microbiological testing; bacterial endotoxins, and other items.The guidance also reviews how to address other required CMC data for individualized ASO drug products, giving advice about how to assess stability when extended storage conditions might be necessary.If a sponsor is considering developing a targeted treatment that could treat more than a few patients, then the suite of guidances that FDA has issued addressing ASO therapies in N of 1 trials would not apply. FDA recommends that sponsors of individualized ASO drug product INDs provide a claim for categorical exclusion from environmental analysis requirements.The FDA is hopeful these draft guidances, once finalized, will help promising drugs reach patients in a timely manner. We are optimistic that the development of these individualized drug products may continue to change the landscape for treating rare diseases, and the FDA is committed to providing resources and guidance to those advancing these technologies to treat patients in need," said Woodcock.Clinical guidance for ASO drug products

CMC considerations

2021Regulatory Affairs Professionals Society.

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FDA rolls out more guidance on 'N of 1' gene therapies - Regulatory Focus

Harnessing the bodys immune system to treat cancer has made remarkable cures possiblebut not for every patient. Now, researchers from UConn Health and the Cleveland Clinic have designed a way to reliably predict who will get good results from immunotherapy, they report in the Journal of Experimental Medicine.

Melanoma, a type of skin cancer, is often deadly once it spreads beyond its original spot. But immunotherapy drugs such as Keytruda have made dramatic cures possible, even for patients whose cancer has spread. About a third see their cancers stop growing or shrink, and 10% have complete remission. The flip side is that two-thirds of patients get no benefit at all.

These immunotherapies are not really as effective as they seem in the advertisements by drug companies, says UConn School of Medicine immunologist Beiyan Zhou. And the treatments take time. It can take at least two to four months, and as long as a year, to tell if a patients cancer responds to a specific immunotherapy. And if it doesnt, thats four months to a year of additional time to metastasize, when the patient could have been pursuing a different treatment entirely.

Zhou has been working with doctors at the Cleveland Clinic to figure out who will benefit from a specific immunotherapy before they spend time and money on it.

Our study highlights a population of cells that not only is associated with immunotherapy resistance, but its intrinsic genetic signals can be leveraged to identify who will or will not respond to their emerging cancer therapeutics. Collaborative efforts of clinicians, immunologists and bioinformaticians yield these exciting discoveries, says Brian Gastman, a collaborator on the project and the Director of Melanoma & High Risk Skin Cancer Program at Cleveland Clinic.

Gastman had been taking skin cancer samples and blood samples from patients and performing single cell profiling with them. These data were then analyzed at Zhous lab at UConn Health, first using conventional methods to take a lone cell and profile which genes in the cell are active.

Most cancer drug prediction tools rely on genetic analysis of specific mutations. If those mutations are present in the cancer, the tool will predict a certain drug will be effective. But these predictions are often inaccurate. Sometimes the gene with the mutation in question isnt active or doesnt matter to that particular cancer.

Unlike genetic analysis, single cell analysis tell us which genes a cell is actually using. Drugs that target active genes should be more effective than those targeting inactive ones.

Zhou and colleagues at UConn created a tool that used both computational and biomedical models on single cell data to predict whether or not a specific patient would respond to immunotherapy. After identifying a signature gene panel using a new strategy developed in Zhous lab, a predictive model was trained using a published single cell dataset (from Broad Institute of MIT and Harvard), and then tested in additional data from the Cleveland Clinics patient data. The tool, named NiCir (non-invasive circulating T cells model), focuses on the activity of 20 specific genes known to be important in melanoma skin cancer and lung cancer. NiCir achieved 88% accuracy in three different datasets predicting which patients cancers had shrunken in response to a specific immuno-checkpoint inhibitor immunotherapy.

The team is now working on creating an new computational program which will allow the creation of more accurate tools for disease prediction, and to facilitate guided-drug discovery.

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Which Patients Benefit Most from Immunotherapy? This Tool Can Tell - UConn Today - UConn Today

BETHESDA, Md., Dec. 7, 2021 /PRNewswire/ -- The ACMG Foundation for Genetic and Genomic Medicine (www.acmgfoundation.org) announced that it has received a commitment from Spark Therapeutics, Inc. to fund two fellowship training awards in ophthalmic genetics through its Next Generation Fellowship & Training Awards Program. This is the first time in its history that the ACMG Foundation will provide funding for training in this rapidly advancing area of specialty in medical genetics and genomics.

The ACMG Foundation's Next Generation Fellowship & Training Awards Program has worked to address a shortage of medical genetics experts needed to diagnose and treat patients with genetic disorders. To date, the program has funded a total of 60 years of study in genetic and genomic medicine to highly qualified medical students. The partnership between the ACMG Foundation and Spark Therapeutics will help foster medical genetics and genomics expertise for physicians seeking to specialize in the evaluation, diagnosis, and management of genetic eye disease.

"I am delighted to announce the generous gift from Spark Therapeutics, Inc. to fund two fellowship positions in ophthalmic genetics with an emphasis on inherited retinal diseases," said Max Muenke, MD, FACMG, CEO of the American College of Genetics and Genomics. "Healthcare professionals experienced in ophthalmic genetics have been at the forefront of helping individuals and families affected with inherited eye diseases. Recent successes in discovering genetic variants and conditions known to contribute to eye disorders and developing and delivering gene therapies for specific eye conditions have the potential of not just managing but laying a foundation towards curing these disorders. With the continually evolving advances in genetics and genomics, we need many more ophthalmologists trained in managing hereditary eye diseases and utilizing these novel treatment modalities."

"As we work together to advance novel treatment options for people and families affected by genetic diseases, it is increasingly important that we continue to build on our foundation and understanding of genetics across the healthcare community," said Bartholomew Tortella, MD, FACS, FCCM, and head of medical affairs, Spark Therapeutics. "Diagnosing and treating inherited eye diseases is complex, and programs such as the ACMG Foundation fellowship focused on ophthalmic genetics are a step forward in supporting patient communities."

Bruce R. Korf, MD, PhD, FACMG, president of the ACMG Foundation said, "A remarkably high proportion of retinal disorders have a genetic basis. Training specialists who are able to use the powerful approaches of genetic and genomic medicine in this area not only will benefit patients with genetic eye disorders but serves as a model for the integration of genetics and genomics across all of medicine."

The ACMG Foundation has stated it is eager to also work with other specialties to ensure that pediatricians, oncologists, obstetricians and other specialties are able to add genetic studies to their years of schooling.

About the ACMG Foundation for Genetic and Genomic Medicine

The ACMG Foundation for Genetic and Genomic Medicine, a 501(c)(3) nonprofit organization, is a community of supporters and contributors who understand the importance of medical genetics and genomics in healthcare. Established in 1992, the ACMG Foundation supports the American College of Medical Genetics and Genomics (ACMG) mission to "translate genes into health." Through its work, the ACMG Foundation fosters charitable giving, promotes training opportunities to attract future medical geneticists and genetic counselors to the field, shares information about medical genetics and genomics and sponsors important research. To learn more and support the ACMG Foundation mission to create "Better Health through Genetics" visit http://www.acmgfoundation.org.

Note to editors: To arrange interviews with experts in medical genetics, contact ACMG Senior Director of Communications and Public Relations, Kathy Moran, MBA at [emailprotected].

CONTACTS:Kathy Moran, MBA[emailprotected]

SOURCE American College of Medical Genetics and Genomics

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ACMG Foundation Receives Gift from Spark Therapeutics for Ophthalmic Genetics Fellowships - PRNewswire

Doctors tell Joe Beard his only shot at survival is a two-organ, bone marrow transplant

ROCKTON This time of year almost everyone has a wish list.

Joe Beardof Rockton has a short but weighty list of needs.

The 40-year-old husband and father of twoneedsa new kidney, a new liver and a bone marrow transplant.

Without them, his chances of living long enoughto see his daughters graduate from high school get slimmer and slimmer each day.

In 2018, Beard was diagnosed witha rare genetic disorder of the immune system called STAT3 gain of function.

An article that appeared in theAmerican Journal of Respiratory and Critical Care Medicine the same year that Beard was diagnosed reported only 28 known cases.

"I have an autoimmune disease that's just running wild, attacking my organs, my body, everything," Beard said.

"Eventually, this is going to kill me. … I don't know if it is six months from now or two years from now, but it's not long."

Seated in the living room of his Rockton home with his wife, Hayley, and daughters Elsie, 6, and Molly, 4, Beard said it was six years ago when the disease first manifested.

"I wasn't feeling well," he said. "I started coughing and losing weight."

Over a three- to four-year period, Beard lost 50 pounds, a lot of weight for anyone of any stature, but even more so for someone who is5-foot-8 andinitially weighed 175 pounds.

At the outset, doctors suspected the fitness buffhad a lung infection and prescribed treatment for such, but the illness persisted.

Eventually, the couple sought care from an immunologist at the University of Wisconsin Hospital in Madison.

"On a whim, she decided to test for genetic diseases," Beard said, "andlow and behold one came back positive for STAT3 gain of function."

STAT3 GOF is a rare genetic disorder of the immune system. The disease is named after the gene, STAT3, and the effect caused by mutations in STAT3 gain of function, meaning the genes protein becomes overactive.

Stolen year:Rockford teen was living her best life when a rare disease attacked her brain

The Beards were referred to the National Institute of Health in Bethesda, Maryland, where the couple visited on a monthly basisfor nearly two years.

"They put me on these experimental drugs to try to control the inflammation," Beard said, "and it seemed to help, but my kidney function continued to decline."

Beard started dialysis about 2 1/2 years ago, about the same time his liver began to fail.

"So now, I am in end-stage renal disease, ESRD, and liver failure," he said."I essentially need a liver and kidney transplant," two vital organs that by themselves won't be enough to save Beard's life because, according to doctors,Beard's immune system will still continue to attack his body.

"So, they said, 'Really what we need to do is give you a new immune system, too,'" Beard said. "So that's where the bone marrow transplant comes in."

A double-organ transplant followed by a bone marrow transplant is a rare procedure, andmultiple hospitals declined to perform the surgeriesbefore theUniversity of Pittsburg Medical Center, one the country'sleading hospitals in performing organ transplants, accepted the case.

Beard was evaluated in January andinformed in March that he was not a candidate for a traditional cadaver-donor transplant because he neededtwo organs and lives more than 500 miles away from the hospital.

"But then they said, 'You could do living donors. If you can find someone to donate half their liver and then another person to donate a kidney and some bone marrow, we'll do it.'"

The Beards'excitement over the news was tempered by their insurance provider. Theywere told the combinations of procedures was "experimental" and would not be covered.

After seven months of filing appeals, submitting letters from doctors and threats of lawsuits, adoctor independent of the Beards and their insurance provider reviewed the case and determined thedouble-organ and bone marrow transplants wasBeard's best option.

"Based on that and per our current laws, they (the insurance provider) had to change their opinion to match the external reviewer," Beard said. "So, we got approved."

Hayley explained not one, but two donors are needed, one to provide the liver, the other to provide a kidney and bone marrow.

Kidney donation is the most common type of living-donor transplant. Individuals can donate one of their two kidneys, and the remaining kidney is able to perform the necessary functions.

As for liver donors, only a portion of the liver is removed and in a matter of months, the donor's liverwill regenerate and perform as normal.

"They'll take up 60 percent of your liver and within three months it will grow back up to 98 percent," Hayley said. "They just said it won't look the same."

Beard said his first choice for donors were his three siblings, all of whom were tested and were found to have the same genetic disorder, which was passed down to them from their father.

Of the four, Beard is the sickest.

"My full sister has no health problems whatsoever, and my other two half siblings have minor health problems, and my dad's been fine."

For the time being, Beard receives weekly infusions of donor antibodies and four days a week he undergoes home dialysis.

He described what is atbest a love-hate relationship with hisdialysis machine, a wonderful piece of technologythat removes waste from his blood and keeps him alive and its a ball and chain that zaps him of his energy and has to go with him when traveling.

"I feel like a bad father sometimes," he said, "because I can't play with my girls."

One of the joys of fatherhoodis teaching achild learn to ridea bike, an undertaking that Beard has had to relinquishto Hayley.

And yet, the dialysis machine has createda special bond betweenBeard and his girls.

Elsie is tasked with entering her father's blood pressure numbers from the dialysis machineinto an app on the family's iPad. Molly pushesthe save button before the information is forwarded to the DaVita Roxbury Dialysis Center wherea dialysis nurse remotely monitor's Beard's health.

More: Generations at Neighbors opens new dialysis unit

Because of his compromised immune system, Beard doesn't stray far away from home other than to go to work at Taylor Co., a Rockton-based manufacturer of commercial food service equipment.

Beard,an electrical engineer, called the company's management team "gracious" and "very accommodating" as they haveprovided him with his own office and allowhim to work from home as his health dictates.

"People ask me, 'How can you still work? I don't know. I guess I'm just trying to keep things as normal as possible and to provide for, you know, the kids and my wife.

"I told my boss, 'This is a good release for me because it makes me forget about things. For a moment, I'm normal.'"

The Beards said it is their faith that holds them up each day and are blessedto have the support of family and friends who pitch in on a moments notice to care for their daughters when needed.

Still, the family is concerned about two looming deadlines.

The first is Jan. 1 when Taylor Co. changes its insurance provider. TheBeards fear they may have to endure another lengthy and contentious processto convince the new insurer to cover thesurgeries.

The other deadline is more murkyand more daunting.

"They want to do the transplants as soon as possible because, you know, I am declining every day. And there's going to come a point when I'll become too ill to receive a transplant. So, they want to do this while I'm still healthy and have enough energy to get through the surgeries."

Chris Green: cgreen@rrstar.com; @chrisfgreen

Register to be a potential donor atlivingdonorreg.upmc.com. TypeJoseph Beard in the Donation to spot.

To help the family with travel and expenses, donations can be sent to:

Roscoe United Methodist Church

C/O Joseph Beard Transplant Fund

10816 Main St.,

Roscoe, IL 61073

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'This is going to kill me': Rockton man with rare genetic disorder in need of 2 live donors - Rockford Register Star

ATLANTA, Dec. 9, 2021 /PRNewswire/ -- Atlanta- and New York-based Moss & Gilmore LLP announced today the settlement with the U.S. Department of Justice ("DOJ") and State of Georgia of a False Claims Act ("FCA") lawsuit against Defendants Jeffrey M. Gallups, M.D. ("Dr. Gallups"), Milton Hall Surgical Associates, LLC ("MHSA") and Entellus Medical, Inc. on behalf of its client, Dr. Myron Jones, an ear, nose and throat doctor and a board certified otolaryngologist. Dr. Jones is a former Army Colonel and Active Duty U.S. Army Otolaryngologist who has been practicing medicine for over thirty four years and who was employed by MHSA from 2015 to 2017.

Defendant Georgia-based Milton Hall's ENT Institute website (http://www.entinstitute.com), provides that "The Ear, Nose & Throat Institute provides exceptional treatment and care for ear, nose and throat disorders including balloon sinuplasty, allergy treatments, sleep apnea and snoring treatment, hearing aids, voice therapy, tonsils and adenoids. Milton Hall serves the Atlanta, GA area with 13 locations in Gainesville, Dawsonville, Cumming, Lawrenceville, Suwanee, Alpharetta, Marietta (East Cobb), Buckhead (Atlanta), Windy Hill (Atlanta), Stockbridge, Peachtree City, and White Oak (Newnan) Georgia."

According to the Department of Justice website and Settlement Agreement, MHSA and Dr. Gallops, while not acknowledging wrongdoing, will pay to DOJ $3,068,434 ("Settlement Amount") to resolve allegations in the lawsuit that it knowingly violated the FCA and the Georgia False Medicaid Claims Act for, among other things, the following:

First, between 2015 and 2017, Dr. Gallups caused MHSA and/or MHSA's physician employees to order medically unnecessary genetic and toxicology tests from Next Health, LLC ("Next Health") for their patients and, in return for these referrals, Dr. Gallups was paid illegal remuneration in the form of a percentage of the revenues that Next Health received from Medicare, Medicaid and TRICARE.

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Second, between 2014 and 2018, Dr. Gallups caused MHSA and/or MHSA's physician employees to order various products associated with balloon sinuplasty surgery from Entellus Medical, Inc., which was acquired by the Stryker Corporation (NYSE:SYK) in 2018 (collectively "Entellus"), and Entellus offered and provided Dr. Gallups and MHSA with various forms of illegal remuneration which included, but was not limited to, trips meals, and monetary payments in order to induce Dr. Gallups to order MHSA physicians and employees to: (1) increase the number of sinuplasty surgeries that they performed; and (2) perform medically unnecessary balloon sinuplasty surgeries. In return for the illegal remuneration from Entellus, Dr. Gallups insisted that MHSA employees and physicians order various products from Entellus and instructed MHSA physicians and employees to exclusively use Entellus products.

As part of the lawsuit, Entellus also agreed to settle these allegations against itself, while also not acknowledging wrongdoing, and to pay to DOJ $1,2000,000.

With respect to the allegations concerning Next Health, LLC, on October 21, 2021, before the U.S. District Court for the Northern District of Georgia, Dr. Gallups pleaded guilty to health care fraud in case number 1:21-cr-00370. Dr. Gallup's sentencing in this criminal action is currently scheduled for February 11, 2022.

In the event that Dr. Gallups and/or MHSA fails to pay the entire Settlement Amount within twelve months of the execution of the November 30, 2021 Settlement Agreement, a Consent Judgment wherein Dr. Gallups and MHSA acknowledge their joint and several liability and debt owed to DOJ in the amount of $5,388,863, plus post-judgment interest, will be enforced by DOJ.

DOJ's press release can be found at https://www.justice.gov/usao-ndga/pr/dr-jeffrey-m-gallups-and-entellus-medical-agree-pay-42-million-resolve-false-claims-act.

The whistleblower physician, who was awarded 20% of all payments to be received under each of the Settlement Agreements by DOJ, was represented by Raymond L. Moss at Moss & Gilmore LLP, who initially brought this FCA action on behalf of the whistleblower, the U.S. Government and the State of Georgia against the Defendants in 2017.

"The whistleblower, Dr. Myron Jones, a decorated former Army Colonel, bravely and tenaciously brought what he believed to be very troubling practices to light as described in his lawsuit in order to seek to protect vulnerable patients and stop government fraud and abuse and illegal kick-back arrangements, which undermine quality and affordable healthcare", said Raymond Moss.

The case, brought in the United States District Court for the Northern District of Georgia, is captioned, United States ex rel. Myron Jones, M.D., et al. v. Milton Hall Surgical Associates, LLC d/b/a The ENT Institute and a/k/a Ear, Nose & Throat Institute, Jeffrey M. Gallups, M.D., Entellus Medical, Inc. et al., Civil Action. No. 1:17-cv-2472.

The Government investigation and settlement of these allegations were handled and settled by the United States Attorney's Office in the Northern District of Georgia through Assistant United States Attorneys Paris Wynn and Georgia Assistant Attorney General James Mooney in the Medicaid Fraud Division. The Department of Health and Human Services ("HHS") for the Inspector General also participated in the investigation. The criminal case was handled and resolved by Assistant U.S. Attorney Chris Huber.

The False Claims Act fosters a private-public partnership to fight fraud against the government. The law encourages whistleblowers to file civil lawsuits against companies that are defrauding the government by offering job protection against retaliation and a reward of 15 to 30 percent of the government's civil recovery if the government joins or intervenes in the case. Under the False Claims Act, the United States may recover three times the number of losses, plus civil penalties.

About Moss & Gilmore LLP: With offices in Atlanta and New York, Moss & Gilmore LLP represents whistleblowers in the U.S. and worldwide in federal and state false claim whistleblower and related retaliation cases involving healthcare fraud and military procurement fraud. Moss & Gilmore LLP represents whistleblowers in cases under the False Claims Act and claims under the U.S. Securities and Exchange Commission, Commodity Futures Trading Commission involving securities and commodities fraud and IRS whistleblower reward programs. For more information, visit http://www.mossgilmorelaw.com.

CONTACT Raymond MossMoss & Gilmore LLP(678) 381-8601rlmoss@mossgilmorelaw.com

Cision

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SOURCE Moss & Gilmore LLP

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ENT Practice Milton Hall Surgical Associates, LLC, Jeffrey M. Gallups, M.D. and Entellus Medical, Inc. Agree to Pay $4,200,000 to Settle Whistleblower...