Editor’s note — the following is a roundup of the news that made headlines at Vanderbilt University Medical Center in 2023.
Whole-genome sequencing agreement
Nashville Biosciences LLC, a wholly owned subsidiary of Vanderbilt University Medical Center, and Illumina Inc., a global leader in DNA sequencing and array-based technologies, announced an agreement with Amgen, a global biopharmaceutical company, to whole-genome sequence approximately 35,000 DNA samples.
The sample cohort is primarily made up of DNA from African Americans, who are currently underrepresented in research for the clinical applications of genomics, including drug target discovery. This cohort will be the largest datasets of genomes of its kind to date.
It’s widely recognized that most genomic datasets are drawn from people of European ancestry. This lack of diversity in genomic data has created a gap in the scientific understanding of the underlying genetic causes of disease and inhibits equitable access to precision health therapies.
Accelerating diversity, equity, inclusion in biomedical research
VUMC and Vanderbilt University launched a $17 million multiyear transformative program with support from the National Institutes of Health (NIH) to accelerate diversity, equity, inclusion and belonging in the biomedical research community.
The institutions are building on prior successes in recruitment to strengthen hiring, promotion and retention efforts for diverse, early-career investigators as a foundational element of the Vanderbilt Faculty Institutional Recruitment for Sustainable Transformation Program (V-FIRST). V-FIRST is funded by the NIH Common Fund Faculty Institutional Recruitment for Sustainable Transformation (FIRST) program as part of its third round of awards.
Project seeks to improve oversight of AI technology in health care systems
VUMC and Duke University School of Medicine were awarded a $1.25 million grant from the Gordon and Betty Moore Foundation for the project “Measuring Artificial Intelligence (AI) Maturity in Healthcare Organizations.”
Working with the Coalition for Health AI (CHAI) and the University of Iowa, a team of experts are leveraging the grant to develop a maturity model framework. The project leads are Peter Embí, MD, MS, and Laurie Novak, PhD, MHSA, from VUMC and Michael Pencina, PhD, and Nicoleta Economou, PhD, from Duke.
This framework will outline the essential capabilities that health systems must establish to ensure they are well prepared for the trustworthy utilization of AI models.
Repairing donor lungs rejected for transplant
Only 20% of donor lungs are in sufficient condition for transplantation, which means that many people die every day while waiting on the transplant list. Discovering new ways to increase the supply of donor lungs is an urgent problem and is desperately needed to save lives of patients with chronic lung disease.
A Vanderbilt team discovered that donor lungs rejected for transplant can be repaired using cross-circulation with a xenogeneic (swine) host.
In this system, a declined human donor lung is connected via catheters to a live swine, which serves as a bioreactor. The swine provides critical physiologic and hormonal support needed to support the recovery of the lung.
Grant aids effort to increase efficiency of conducting clinical trials
Researchers in the Vanderbilt Institute for Clinical and Translational Research (VICTR) were awarded two five-year federal grants totaling $51 million to harness new and existing approaches for boosting recruitment and removing roadblocks to the efficiency of conducting clinical trials throughout the country.
The grants, from the National Center for Advancing Translational Sciences, part of the NIH, recognized the expertise, leadership and plethora of clinical research tools developed over the past several years at VICTR, home of VUMC’s NIH-funded Clinical and Translational Science Award.
Initiative to advance evidence generation in complex disease populations
nference, a science-first software company transforming health care by making biomedical data computable, and VUMC announced a strategic agreement aimed at advancing research through the deployment of nference’s state-of-the-art federated clinical analytics platform. By leveraging the power of federated AI and machine learning, this collaboration will expand clinical insights in key research areas.
Record year for solid organ transplants; transplant programs grow at fast rate
The Vanderbilt Transplant Center performed a record number of solid organ transplants in fiscal year 2023 (FY 23) — 665 life-saving procedures among its adult and pediatric programs. The total number of transplants from FY 23, the period between July 2022 and the end of June 2023, rose 3% from the 645 transplants during the same period in FY 22.
Vanderbilt’s lung transplant program had a record fiscal year, with 80 transplants, a 29% increase over FY 22. Growth was also driven by kidney transplants, increasing 7% to 315 adult and pediatric transplants.
In the Adult Transplant program in FY 23, teams performed 301 kidney transplants (including simultaneous pancreas-kidney transplants and pancreas-after-kidney transplants), 112 heart transplants, 130 liver transplants, and 80 lung transplants.
Pediatric transplant teams with Monroe Carell performed 14 kidney transplants, 21 heart transplants and seven liver transplants.
The Vanderbilt Transplant Center has emerged over the past five years as an international leader in solid organ transplantation.
Among the fastest-growing programs has been Vanderbilt’s heart transplant program, which performed a combined total of 429 transplants during the past three years, more than any other center in the country. Key to the success of the program has been commitment to a multidisciplinary effort that involves physicians, nurses, social workers, pharmacists and others, some of whom travel across the state of Tennessee and beyond to care for patients with advanced heart failure who may need transplants and to recover donor hearts for patients awaiting transplant.
ICU antibiotics may be safe for kidneys
Two ‘big gun’ antibiotics thought to cause kidney failure in ICU patients with a severe bacterial infection, especially when combined with another antibiotic, may be safer for the kidneys than previously reported, following a randomized trial led by Vanderbilt University Medical Center.
The findings on cefepime vs. piperacillin/tazobactam were released simultaneously in JAMA and during a presentation from VUMC first author Eddie Qian, MD, assistant professor of Medicine in the Division of Pulmonary and Critical Care Medicine, at ID Week 2023 in Boston.
The study by Qian, co-senior author Todd Rice, MD, professor of Medicine, and colleagues was named among the most popular JAMA articles published in 2023.
Grant aids study of relationship between COVID-19 and diabetes
Researchers at VUMC received a four-year, $28 million grant from the National Institute of Diabetes and Digestive and Kidney Diseases, part of the NIH, to study the relationship between COVID-19 and diabetes.
Several studies have found that infection with SARS-CoV-2 and a COVID-19 diagnosis are associated with a higher risk for the development and progression of both Type 1 and Type 2 diabetes, possibly through the infection of insulin-secreting beta cells, increased insulin resistance, inflammation and fibrosis and other biological processes.
The COVID-19 and Diabetes Assessment (CODA) Study is identifying and recruiting 1,600 participants through the T1D Exchange, a research network of diabetes centers, and PCORnet, a national research network funded by the Patient-Centered Outcomes Research Institute, which engages hundreds of health care sites with access to electronic health record data from more than 30 million patients annually.
Ambulatory Surgery Division formed
With year-over-year growth in surgical volume, Vanderbilt Health formed a new Ambulatory Surgery Division. Within the Vanderbilt Health System approximately 85,000 surgical operations are performed each year, of which 70% are ambulatory.
The new division resides within the Ambulatory Enterprise led by an executive team. David Penson, MD, MPH, MMHC, chair of the Department of Urologic Surgery, serves as the new division’s Executive Medical Director. Stephen W. Marshall, MBA, Senior Vice president of Operations for Surgery Partners, was named Vice President and Chief Operating Officer for the division, and Chris Wilde, MBA, CPA, Vice President and Divisional Chief Financial Officer, serves as the division’s director of Finance.
VUMC joins research initiative to improve patient outcomes
The Patient-Centered Outcomes Research Institute (PCORI) named VUMC to a select group of health systems nationwide brought together to accelerate the implementation of medical research results that will improve patient outcomes.
As a participant in PCORI’s Health Systems Implementation Initiative (HSII), VUMC uses its expertise in health care delivery to develop and implement strategies to adopt new evidence beneficial to patient care. The team is evaluating practice change efforts, including what strategies work best in different contexts and their impact on patient care.
Consuelo Wilkins appointed to NASEM committee for Unequal Treatment Revisited
Consuelo Wilkins, MD, MSCI, Senior Vice President and senior associate dean for Health Equity and Inclusive Excellence and professor of Medicine at VUMC, was appointed to the National Academies of Sciences, Engineering and Medicine (NASEM) committee for Unequal Treatment Revisited.
The 17-person committee is comprised of national leaders with a range of relevant expertise across medicine, public health and economics.
Their goal is twofold: examine the current state of racial and ethnic health care disparities in the U.S. and provide an update on the NASEM’s last report, which was published in 2003.
Research platform to explore early-childhood determinants of health
Having received a seven-year, $51 million grant from the NIH, biomedical scientists at VUMC launched a research platform devoted to molecular underpinnings of early-childhood determinants of health.
The project, called ELVIS, or, less connotatively, the ECHO Laboratory core at Vanderbilt for Integrated Sample biobanking and processing, is part of an expansion of ECHO, the NIH’s multi-center Environmental Influences on Child Health Outcomes program, which launched in 2016 with an initial $157 million in funding, including to teams at VUMC.
Under ELVIS, biospecimens collected around the country from participants in ECHO’s long-term research cohorts arrive for biobanking and analysis at VUMC, and data from the ensuing molecular assays flows to ECHO-qualified researchers everywhere via a secure web portal.
Renovation of pediatric operating rooms
Monroe Carell Jr. Children’s Hospital at Vanderbilt began the first major renovation of its operating rooms since the hospital opened 19 years ago.
The first phase of renovations will overhaul 10 of the hospital’s 18 ORs, focusing on two surgical suites at a time. The first two rooms to undergo renovations will be the cardiac room and a multiuse room used primarily for robotic surgery cases. Each room will take about 13 weeks to complete.
Alliance for Genomic Discovery
Illumina Inc., a global leader in DNA sequencing and array-based technologies, in collaboration with Nashville Biosciences LLC, a leading clinical and genomic data company and wholly owned subsidiary of VUMC, announced the five founding new members of the Alliance for Genomic Discovery.
The multiyear agreement aims to accelerate development of therapeutics through large-scale genomics and the establishment of a preeminent clinical genomic resource. Member organizations AbbVie, Amgen, AstraZeneca, Bayer and Merck will co-fund the whole-genome sequencing (WGS) of 250,000 samples and have access to the resulting data for use in drug discovery and therapeutic development.
Systemic lupus erythematosus finding
Targeting iron metabolism in immune system cells may offer a new approach for treating systemic lupus erythematosus (SLE) — the most common form of the chronic autoimmune disease lupus.
A multidisciplinary team of investigators at VUMC discovered that blocking an iron uptake receptor reduces disease pathology and promotes the activity of anti-inflammatory regulatory T cells in a mouse model of SLE. The findings were published in the journal Science Immunology.
Potential to save taxpayers millions on Medicare generic oncology drugs
The U.S. government could save taxpayers between $228 million and $2.15 billion a year if insurers who operate its Medicare Part D plans purchased seven generic oncology drugs at the same prices obtained by the Mark Cuban Cost Plus Drug Company (MCCPDC), according to a study published in the Journal of Clinical Oncology,
The VUMC study, led by Ruchika Talwar, MD, a urologic oncology fellow, estimated potential savings by switching to MCCPDC prices with the implication that Medicare Part D plan sponsors and beneficiaries are likely overpaying for these self-administered generic oncology drugs.
Antibody against RSV, human metapneumovirus discovered
VUMC and Stanford University researchers discovered a potent, cross-neutralizing human monoclonal antibody against the respiratory syncytial virus (RSV) and human metapneumovirus.
The findings, published in Cell Host and Microbe, describe not only the potency of the RSV-199 antibody but the mechanisms through which it cross-neutralizes eight different strains of RSV and hMPV infection in mice. This discovery marks a crucial step in developing and designing a single vaccine against both pathogens.
Diabetes medication and heart risk for older patients
GLP1 receptor agonists — a class of diabetes medications — are associated with fewer major adverse cardiovascular events than another type of diabetes drug (DPP4 inhibitors) in older veterans with no prior heart disease. The findings, reported in Annals of Internal Medicine, will aid clinicians in choosing a diabetes drug regimen for older patients.
Tumor mutation burden discovery
The expected course of a patient’s cancer prognosis has traditionally been judged by its type, stage and microscopic aggressiveness, but patients with the same presentation can still have widely divergent outcomes. Researchers from Vanderbilt-Ingram Cancer Center have discovered that differences in tumor mutation burden are a major reason for this divergence.
The study, published in JCO Precision Oncology, revealed that mutation burden is a fundamental predictor of survival, independent of the clinical presentation metrics currently used. The researchers state in the study that mutational indices can be “used to predict disease course as effectively as (cancer) stage or grade.”
Monroe Carell’s heart-lung support program honored
For the past 15 years Monroe Carell’s heart-lung support program has achieved the highest level of recognition available from the Extracorporeal Life Support Organization (ELSO).
This year, the program, the first in Tennessee to use extracorporeal membrane oxygenation (ECMO), garnered the premium designation bestowed by the society — the Platinum Level of Excellence in Life Support by ESLO.
Study to compare sedatives used during tracheal intubation
VUMC received a $7 million, five-year funding award from PCORI to compare two sedatives used to place breathing tubes in the emergency department or intensive care unit.
The study will compare the effectiveness of ketamine versus etomidate during tracheal intubation of 2,364 critically ill adults at five centers.
Gastric cancer development finding
Fibroblast cells play key roles in the repair of damaged tissue and in pathological scarring. Researchers at VUMC have uncovered evidence of their direct involvement in the development of gastric cancer.
The findings, published in the journal Gastroenterology, could lead to novel interventions to prevent cancer of the stomach, the third leading cause of cancer deaths worldwide after lung and colorectal malignancies.
Genetic counseling continuing education initiative
Upon receiving a $9.7 million grant from The Warren Alpert Foundation (WAF), the Perelman School of Medicine at the University of Pennsylvania (Penn Medicine) partnered with Vanderbilt University School of Medicine and three other institutions to design and provide continuing education programs for genetic counselors.
This is the first of its kind as there are currently no formal training programs for continuing education in the field of genetic counseling.
Study sheds new light on how lungs develop
Using a four-dimensional microscope that allows them to watch a tissue putting itself together, researchers at VUMC achieved a rare feat in science — they shattered a long-standing dogma about how the lung develops.
Their tour de force raises the possibility that one day scientists will be able to repair damaged lungs by triggering the growth of normal tissue, and that doctors will be able to prevent the development of lung disease in babies born prematurely.
Immune system T cells become dysfunctional soon after encountering a tumor
Immune system T cells that should be able to kill cancer cells become dysfunctional or “exhausted” within hours of encountering a tumor, according to a study reported in Nature Immunology.
The surprising findings have implications for cancer immunotherapies that aim to harness the tumor-killing power of T cells, and they challenge existing ideas about how T cells become exhausted, said Mary Philip, MD, PhD, assistant professor of Medicine in the Division of Hematology and Oncology at VUMC.
Vanderbilt-Ingram Cancer Center earns MERIT Award
Vanderbilt-Ingram Cancer Center earned a Merit Extension Award from the National Cancer Institute (NCI) in recognition of more than a decade of sustained exceptional progress.
The Merit Extension Award provides two additional years of funding from the NCI Cancer Center Support Grant (CCSG), adding $15 million to the $36 million grant that the NCI awarded to VICC in 2020. VICC became eligible for the Merit Extension Award after receiving two consecutive “exceptional” ratings, the highest possible, for the CCSG in 2015 and 2020. The ratings are based on a rigorous evaluation process conducted by nationally recognized peer reviewers.
Research proves environmentally sustainable cost savings for MRIs, CTs
A collaboration between Royal Philips and VUMC, initially announced in May, proved that sustainable initiatives in health care can be both environmentally friendly and cost-effective.
The two entities announced initial results of a research collaboration to decarbonize the health system’s radiology department.
The assessment indicated that circular business models, such as upgrades, can reduce total cost of ownership of a magnetic resonance imaging (MRI) system by up to 23% and carbon emissions by 17%, and for CT, refurbished systems and equipment upgrades can contribute to reducing costs of ownership by up to 10% and 8% respectively, and reducing carbon emissions by 6% and 4% respectively.
Study finds polygenic risk score doesn’t enhance prostate cancer screening
A prostate cancer polygenic risk score (PRS) has limited utility for enhancing prostate cancer screening, according to a study published in JAMA Internal Medicine.
VUMC researchers led the study to evaluate whether a prostate cancer PRS, an indicator of an individual’s “burden” of prostate cancer-associated genetic variants, could improve risk prediction compared to an available clinical risk calculator. While the prostate cancer PRS improved detection of all prostate cancers, it did not improve prediction of aggressive cancers, the researchers found.
Behavioral interventions to treat childhood obesity
VUMC received a $10 million, five-year research funding award from PCORI to study the ideal “dose” of behavioral interventions to treat childhood obesity in rural and minority communities across Tennessee and Louisiana.
Researchers are enrolling 900 parent-child pairs, with children ages 5 to 17 who have obesity and are from rural and minority communities in Tennessee and Louisiana, where childhood obesity rates are among the highest in the country. Underserved communities often have unequal access to evidence-based obesity interventions, contributing to the higher rates among these populations.
Viewing earliest events leading to development of cancer
Researchers at VUMC identified the mechanism by which the enzyme and tumor suppressor SETD2 prevents the propagation of these errors, and thus safeguards the integrity of the genome.
Their discovery, reported in the Proceedings of the National Academy of Sciences (PNAS), provided a remarkably detailed view of the earliest events leading to the development of cancer, and of potential new ways to prevent it.
Potential new targets for antibacterial drugs to combat C. diff
Iron storage “spheres” inside the bacterium C. diff — the leading cause of hospital-acquired infections — could offer new targets for antibacterial drugs to combat the pathogen.
A team of Vanderbilt researchers discovered that C. diff (Clostridioides difficile) produces the spheres, called ferrosomes, and that these structures are important for infection in an animal model. The findings, reported in the journal Nature, are also a rare demonstration of a membrane-bound structure inside a pathogenic bacterium.
Linking gene network and pancreatic beta cell defects to Type 2 diabetes
In a collaborative effort co-led by teams from VUMC and the University of Michigan, a comprehensive study that integrates multiple analytic approaches linked a regulatory gene network and functional defects in insulin-producing pancreatic beta cells to Type 2 diabetes.
The study, published in the journal Nature, lays the foundation for identifying additional early disease-driving events for Type 2 diabetes and also provides a template for identifying regulatory networks that drive other diseases.
Study sheds light on mechanisms of small cell lung cancer tumors
The largest genomic analysis ever conducted of small cell lung cancer tumors (SCLC) identified genetic subtypes and provided insights into the mechanisms of this aggressive and deadly cancer.
The study, published recently in Cancer Discovery, reveals cues toward the development of personalized treatment approaches.
Possible avenue to improved immunotherapy for colorectal cancer
By mapping the cellular and molecular geography of colorectal cancer, VU and VUMC researchers collaboratively discovered why most colorectal tumors escape detection and destruction by the body’s immune system.
Their findings, reported in the journal Cell, could lead to new ways to bring these evasive tumors into the harsh and potentially curative light of immunotherapy.