Grants Funded

Abstract

Impact Statement: Surgical site infection (SSIs), such as those associated with implant-based breast reconstruction (IBBR), remain a common cause of morbidity, mortality and cost. It is estimated that SSIs account for up to $10 billion annually in health care expenditures. Although the microbiome has been implicated in a number of disease processes, little if any research has explored its role in IBBR. This pilot study will show whether microbiome composition at the time of mastectomy and over the course of IBBR differs between patients that do and do not develop infection. A better understanding of the microbiome in the context of SSIs (in general), and IBBR specifically, has the potential to reduce cost and suffering immeasurably by providing insights into rational new strategies to mitigate them.

Project Summary: The long-term goal of our research program is to develop more effective strategies to reduce infection (and reconstructive failure) in implant-based breast reconstruction (IBBR). Despite the use of standardized protocols and the development of adjunct techniques (e.g., intraoperative laser angiography), implant infection rates remain as high as 30%. The objective of this application is to document and compare the abundance, diversity and composition of the breast microbiome over time using metagenomics sequencing analysis in patients who develop infections during/after IBBR, with those who do not. Our central hypothesis is that the breast microbiome of patients that do or do not have postoperative complications differ and that we can identify species within a patient's breast microbiome that go on to cause infections/loss. The rationale for the proposed study is that the reported rates of infection for IBBR contrast starkly with reported infection rates for other similar operations (e.g., prosthetic joint placement (1%) and more readily approximate the CDC expected surgical site infection (SSI) rate of clean-contaminated (3-11%) or even contaminated (10-17%) wounds. It is known that healthy and cancerous breast tissue contains distinct, robust and diverse microbiota. A better understanding of breast microbiota during IBBR has the potential to lead to novel preventive and treatment strategies. We will objectively test the feasibility of our central hypothesis using our robust prospective tissue bank and dataset that includes patients who experience infection after IBBR as well as matched controls. We will use shotgun metagenomic sequencing to quantify all microbial species and their potential functions in the tissues of infected patients and compare them to a group of case-matched control patients that had no infection. The results from taxonomic and functional profiling of microbiota will be merged to identify similarities and differences among the samples and groups. Differential abundance analysis will be performed to identify statistically significant differences between patients that do and do not develop an infection following reconstruction with a goal to identify pathogenic microbes that potentially contribute to infection and implant failures, as well as a predictive signature and potential therapeutic target for postmastectomy implantation infection.

Biography
Dr. Katz is an Associate Professor of Plastic Surgery at the University of Virginia, with joint appointments in the Department of Biomedical Engineering and the Department of Medicine. After graduating from Duke University in 1989 with a Bachelor's degree in Neuroscience, Dr. Katz obtained his M.D. from the University of Michigan Medical School, where he was president of the Alpha Omega Alpha National Honor Medical Society as well as a Hewlett-Packard Top Medical Graduate. His next 8 years were spent at the University of Pittsburgh Medical Center for General and Plastic Surgery training. While a surgical resident in Pittsburgh, Dr. Katz helped pioneer the conception, detection, description, and early characterization of multipotent stem cells derived from adipose tissue (and is one of only two court-determined inventors on the issued composition-of-matter patent describing such cells). Upon joining the staff at UVA in 2001, Dr. Katz initiated the Laboratory of Applied Developmental Plasticity with a focus on the biology and therapeutic potential of adipose-derived cells and factors. He was awarded The Academic Scholar of the American Association of Plastic Surgeons from 2002-2004, he is a member of The American Society of Plastic Surgeons (ASPS), The American Association of Plastic Surgeons (AAPS), and The Plastic Surgery Research Council, and serves on the Editorial Board of Annals of Plastic Surgery. Dr. Katz is an original founder of StemSource, Inc, a company based on his pioneering work with adipose stem cells and which is now Cytori Therapeutics (CYTX). In addition to his clinical responsibilities, Dr. Katz is also a co-founder, past president and board member of The International Federation for Adipose Therapeutics and Science (iFATS), as well as a founder and board member of two additional biotechnology companies. His current research funding is from the NIH and the Department of Defense.