Neutrophil microRNAs Promote Genomic Instability and Carcinogenesis in Inflamed Intestinal Tissue

Principal Investigator: Ronen Sumagin, PhD   Normally immune cells like polymorphonuclear neutrophils (PMNs) protect our body against invading pathogens, but sometimes they go overboard. Accumulating in tissue they can cause cell injury in the GI tract, leading to the development of Inflammatory Bowel Diseases (IBD) and potentially, colorectal cancer. While neutrophils can drive inflammation, it remains unclear just how they contribute to tumor development. Supported by funding from a Digestive Health Foundation, Ronen Sumagin, PhD, a faculty member in the Department of Pathology at Northwestern Medicine and colleagues plan to define the mechanism that allows neutrophils to both promote abnormal cell mutations and inhibit DNA repair genes. They will also study if neutralizing these harmful effects can prevent increased mutations and cancer. The research team will specifically explore the potential use of targeted inhibition PMN-derived miRNAs as an antitumor therapy and test the theory that PMNs play a critical role in causing genomic instability, cellular transformation and tumor growth. Recurring PMN-mediated injury to the intestinal lining is a hallmark of IBD and significantly enhances the risk of developing colorectal cancer (CRC). Current IBD therapies include steroids, which have harsh long-term side effects. Confirmation of the role of PMNs, and identification of specific targets to inhibit PMN activity in patients with IBD, could help reduce the need for steroids and lead to the development of future diagnostics for colon cancer. Preventative treatment in this vulnerable patient population—many of them young adults—could significantly reduce their risk of colon cancer, which typically increases with age. Beyond IBD patients, Dr. Sumagin’s groundbreaking discovery of the relationship between inflammation and cancer could have far-reaching...

A Multidisciplinary Collaboration to Minimize Diversion of Opioids

Principal Investigator: Jonah J. Stulberg, MD, PhD, MPH A surplus of prescription pain killers continues to fuel the drug crisis in America. Accidental overdose of opioids have surpassed motor vehicle crashes in this country. Nearly two-thirds of opioid pills prescribed to Digestive Health Center (DHC) patients now go unused, leaving them vulnerable to abuse or misuse within our communities. Thanks to a Digestive Health Foundation grant, Jonah J. Stulberg, MD, PhD, MPH, a faculty member in the Department of Surgery, plans to launch the nation’s first-of-its-kind intervention project aimed at this growing risk among the DHC patient population. Through education and training, he hopes to change the culture of drug misuse among patients and the prescribing habits of ordering physicians to provide a safer and more effective pain management strategy. The study will include the installation of a one-way, sealed drug collection receptacle within the DHC Clinic; provider training on opioid prescribing risks, benefits and alternatives; and patient education materials promoting opioid medication safety. The grant will support the development of the educational tools and the statistical and project coordinator staff needed to study implementation effectiveness as well as the costs associated with the installation and maintenance of the opioid retrieval box. The ultimate goal is to develop a sustainable model for safe opioid prescribing and optimal pain control, while minimizing societal harm due to a surplus of unused...

Bowel Purge and Change in Pulmonary Function Tests in People with Cystic Fibrosis: A Pilot Study

Principal Investigator: Adam C. Stein, MD Does constipation cause breathing problems? In some individuals with cystic fibrosis (CF), the answer is yes-maybe.  A genetic disorder typically affecting lung function, CF can also cause GI tract issues. Many patients with CF suffer from severe constipation that sometimes lands them in the hospital for intensive management of their condition. Bowel purges can bring relief. After undergoing a bowel preparation—much like one used before colonoscopies—to assist with bowel movement, some CF patients surprisingly reported improvements in their breathing. As a part of the multi-specialty CF clinic at Northwestern Medicine, Adam C. Stein, MD, a faculty member in the Division of Gastroenterology and Hepatology, has seen the debilitating consequences of constipation in patients. He believes there may be a connection between pulmonary function and GI problems, such as constipation. Supported by a grant from the Digestive Health Foundation, Dr. Stein and colleagues will characterize the effect of a single bowel purge on breathing or pulmonary function tests in patients with CF who also have pancreatic insufficiency. They plan to enroll 20 patients in this pilot study by identifying and recruiting potential participants (18 years or older) at the time of their clinic appointment at Lurie Children’s Hospital. Baseline breathing tests will be performed as per the usual routine at clinic visits. Participants will answer a short survey about bowel habits and, within two weeks of their follow up visit, will undergo a bowel prep. The next day at the subsequent clinic visit, breathing tests will be re-administered and participants will complete the same short survey. If data from this novel pilot study reveals...

Metabolomic Biomarkers for the Diagnosis of NASH in the Liver Transplant Population

Principal Investigator: Mary Rinella, MD The most common cause of liver injury in the United States, non-alcoholic fatty liver disease (NAFLD) occurs when extra fat builds up in liver cells. A serious offshoot of NAFLD, nonalcoholic steatohepatitis (NASH) can cause the liver to become inflamed. Those who develop NASH often require a liver transplant. Even after liver transplant, these patients face an uphill battle. They remain at particularly high risk of NASH recurrence, which can lead to graft failure and even death. Currently painful and invasive needle biopsies are the only way to diagnose and stage NASH. As NASH reoccurs, byproducts of the disease process appear in the blood that may provide important clues to disease progression. Supported by a grant from the Digestive Health Foundation, Mary Rinella, MD, a gastroenterology and hepatology faculty member and her co-investigators hope to develop a blood-based alternative by identifying biomarkers that can accurately indicate the onset or recurrence of NASH. The investigators will focus on patients who have undergone liver transplantation at Northwestern Memorial Hospital from 1987 to present. Their pilot study will look at participants from the “Mini-Liver” cohort: patients who have had liver biopsy after transplantation, several of whom have recurrent NASH. Plasma samples are collected from all patients in this group and immediately stored at the time of biopsy for future reference and research studies. Dr. Rinella’s study will involve the use of a validated blood serum-based biomarker panel test (OWLiver assay) that has shown great promise in diagnosing NASH in the non-transplant setting to test the existing biobanked plasma samples. The researchers will also review clinical data drawn...

Perioperative Lidocaine Pharmacokinetics in Patients Receiving Intravenous Lidocaine Analgesia during and after Colorectal Surgery

Principal Investigator: Shireen Ahmad, MD More than 300 patients undergo bowel surgery every year at Northwestern Memorial Hospital for a variety of digestive diseases. Understandably, a chief concern is adequate pain relief. Most patients usually receive narcotic pain medications. While good for controlling pain, they come with a host of side effects ranging from nausea and constipation to sleepiness and confusion. Beginning in September 2016, Northwestern Memorial offered another option as part of a pilot program: intravenously-injected lidocaine. A numbing agent, it also provides pain relief but without the adverse side effects of narcotics. Additionally, lidocaine decreases inflammation and speeds recovery of bowel function after surgery. While many patients benefited from the lidocaine given at doses recommended by experts at other medical centers, a small number experienced side effects that required immediate cessation of the drug. Their metabolism of the pain reliever may have resulted in higher than expected (and higher than potentially safe) levels of lidocaine in the blood stream. Funded by a Digestive Health Foundation grant, a research team led by Shireen Ahmad, MD, an anesthesiology faculty member at Northwestern Medicine, will study blood levels of lidocaine in 40 patients at various times while they are receiving the medication. The aim is to identify predisposing characteristics that put certain patients at risk for lidocaine-induced side effects to better individualize the dosing, safety and effectiveness of the drug. A clearer understanding of the pharmacokinetics of the drug lidocaine will help to maximize its pain-killing properties while minimizing adverse side effects of this promising alternative to narcotics for pain...