abstracts

2022

1. Consequences of Intentional and Unintentional Nonadherence in Inflammatory Bowel Disease Patients Cho, S. M., Waghela R., Saleh, Adam, Abraham, B. Digestive Disease Week, May 2022 [Abs] [HTML] [Poster]

   Introduction: The management of inflammatory bowel disease (IBD), despite its many advances over the years, can be greatly limited by patient nonadherence. Nonadherence can be divided into two broad categories, with intentional nonadherence being primarily driven by the patients' free will while unintentional nonadherence being primarily driven by factors outside patients' control. This study explores the pattern of nonadherence and the impact that specific types of nonadherence can have on IBD complications. Methods: We performed a retrospective analysis of patients from a single-center IBD program from the year 2010 to 2021 who were found to have medical record documentation of nonadherence to their IBD regimen, whether it be for medications, clinic visits, lab evaluations, and/or endoscopic evaluations. We found 58 unique patients to be nonadherent, with a total nonadherence count of 78. Basic demographic data was obtained for the unique patients. The primary analysis was focused on the intentionality of these patients' nonadherence (intentional vs unintentional). Additional data points included type of nonadherence (medications, clinic visits, lab draws, endoscopies), reason for nonadherence, as well as complications (flares, need for escalation of therapy, need for surgery, infection, etc.) Result: At our center, more females (62.1%) than males (37.9%) were nonadherent to their IBD regimen. Of total nonadherence occurrences, 66.7% were intentional and 33.3% were unintentional, and there was no statistically significant association between intentionality and sex. A sheer majority of unintentional adherence was related to insurance and cost. The majority of nonadherent behaviors were largely seen with medications (78%), and this was especially with unintentional nonadherence (96.15%). When comparing between intentional and unintentional nonadherence patients, there was no statistical difference in subsequent flare development, need for escalation of therapy, need for systemic steroids, need for hospitalization, development of EIM, and development of cancer. However, there was a statistical difference (p = 0.029) for a higher need for surgery in unintentional nonadherence. Discussion: Insurance and cost issues are major sources of unintentional nonadherence despite the majority of these patients having insurance, a frustrating reality for both patients and physicians. Most IBD complications appear to occur similarly between intentional and unintentional nonadherence, with the exception being the higher need for surgical intervention in unintentional nonadherence. This highlights the need to maintain active coverage of IBD management due to the complications and higher expenses that could likely be avoided in unintentional nonadherence.

2021

1. Utility of Intestinal Ultrasound in Inflammatory Bowel Disease Patients in Making Management Decisions Saleh, Adam, Perry, C., Abraham, B. American College of Gastroenterology, October 2021
   European Crohn's and Colitis Organization, July 2021 [Abs] [HTML] [Poster]

   Introduction: Intestinal Ultrasound (IUS) has been gaining momentum in the management of patients with inflammatory bowel disease (IBD). Underutilized in the United States(U.S.), we present the impact of IUS in management decisions in a cohort of IBD patients seen at a tertiary center. Methods: This retrospective study analyzed all IBD patients seen at our institution undergoing IUS as part of routine clinical evaluation. Patient demographics, disease type, clinical activity, laboratory markers, and therapy was obtained. Patients with evidence of inflammation based on IUS characteristics of bowel wall thickening, with additional parameters of mural stratification, mesenteric fat, doppler flow, lymph nodes, dilated bowel, free fluid used as adjunct measures were compared to those without IUS features of activity. Subsequent management plan based on findings were evaluated. Results: Of 148 patients seen for IUS (median age 41 (range 18-81), 67% female), 108(73%) had Crohn’s disease (CD), 39(26.4%) had ulcerative colitis (UC), 1(0.7%) had IBD-undetermined (IBD-U) with 111(75%) Caucasians, 9.5% Blacks, 8.8% Asians, and 6.8% Hispanics. Median disease duration was 8 years, range (0-43) with 113(94.1%) on biologic/small molecule therapy and 7(5.8%) on mesalamines. No differences in BMI were noted in those with active disease vs. those in remission. However, we noted 29(19.3%) had fatty liver on ultrasound, which correlated highly with high BMI (31 vs. 24) in those with normal liver (p< 0.05). On IUS, 110(66%) of our patients had evidence of disease activity and 56(34%) were in remission. Inflammatory markers ESR and CRP did not correlate to IUS activity. In our UC patients Mayo score correlated to IUS findings but not Harvey Bradshaw Index (HBI) for CD. For those with positive findings on IUS, 29.5% escalated therapy for their IBD, and 13.3% required change in drug mechanism. For those in remission, the majority of patients 43(84.3%) continued their therapy while 3(5.9%) successfully de-escalated therapy. Discussion: In our study, IUS was useful in providing management decisions in those with active disease especially as there was a lack of correlation to inflammatory markers and HBI scores.

1. SARS-CoV-2 Vaccine Antibody Response in Patients with IBD Garza, M., Saleh, Adam, Maturi, V., Perry, C., Cho, S. M., Abraham, B. American College of Gastroenterology, October 2021 [Abs] [HTML] [Poster]

   Introduction: Patients with inflammatory bowel disease (IBD) are often on immunosuppressive therapies which may reduce the immunologic response to the SARS-CoV-2 vaccine. At this time, there is limited data on vaccine response in patients on different therapies. Furthermore, the CDC does not recommend antibody testing to confirm immunity, and revaccination is not recommended. Methods: Our study evaluated antibody response measured by a quantitative IgG antibody to the spike antigen of SARS-CoV-2 via ELISA in a group of 73 vaccinated IBD patients who have undergone or are receiving infusions of vedolizumab, infliximab, and ustekinumab, or a combination of multiple biologics. All patients have received the 2-dose vaccination and must have completed them for minimum 2 weeks or longer before testing. Statistical analysis was performed by segmenting the patient population into two subgroups of normal ( >20 U/mL) and abnormal (< 20 U/mL) titer levels. Independent T-tests were then performed on specific patient characteristics, inflammatory markers, and medications to determine statistical significance. Results: Responses greater than 20 IU/mL were considered normal responses. Patients older than age 50 were more likely to have abnormal antibody titers after vaccination. There were no differences in antibody response when comparing patients on different biologics including those that were on more frequent dosing (q4 week injections/ infusions vs q8 weeks, or between ulcerative colitis (UC) vs. Crohn’s disease (CD), or in those with biomarker evidence of active disease based on erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) (See Table 1). None of these patients, including those with abnormal titer levels developed COVID infection after vaccination. Discussion: In our study, it was found that only age was a statistically significant predictor among our immunosuppressed IBD patients for antibody response levels. Importantly, even more aggressive combination biological therapies did not appear to affect antibody response in our patient population. Lastly, inflammatory markers and presumably disease activity, did not appear to have a statistically significant impact on antibody response. More studies will be needed to further assess if there is clinical utility in evaluating for vaccine antibody titers in our IBD patients.

1. SARS-CoV Vaccination and IBD Garza, M., Saleh, Adam, Perry, C., Abraham, B. American College of Gastroenterology, October 2021 [Abs] [HTML] [Poster]

   Introduction: We have limited data on the response of the SARS-CoV2 vaccine on patients on immunosuppressive therapies. However, there is concern that the vaccination may not be as effective based on preliminary information from transplant patients. In inflammatory bowel disease, many patients are on biologic therapies to maintain remission. Although the currently approved vaccines are considered safe to use in immunosuppression as they are killed vaccines, we have limited data on the effectiveness in preventing COVID infection in individuals with inflammatory bowel disease (IBD). Case Description/Methods: We present a case report on a 39-year-old female with Crohn's disease who was vaccinated against COVID using the Pfizer vaccine. Two months after vaccination, she developed symptoms of COVID of fever, abdominal cramping, and nausea. She recovered without any sequelae after 8 days. She has been on adalimumab 40mg every two weeks since 2016, previously on vedolizumab, but had worsening gastroparesis. SARS-COV2 antibody titers were not evaluated in this patient after vaccination or before her known infection. Although this was reported in only one of our patients seen in our tertiary referral IBD center, this raises concern of lower efficacy of the SARS-CoV2 vaccination in those on biologic therapy especially anti-TNF treatment such as adalimumab. Discussion: Further evaluation on vaccine response should be considered for future research and our IBD patients on immunosuppressive therapy must be educated on the possibility of getting COVID after exposure despite vaccination. Furthermore, this case highlights the individualization of care that should be provided for individuals with IBD amidst a pandemic.

1. Association of Enteric Infections and Disease Activity in Inflammatory Bowel Disease Kim, C., Garza, M., Maturi, V., Narwankar, M., Saleh, Adam, Perry, C., Glassner, K. Abraham, B. American College of Gastroenterology, October 2021 [Abs] [HTML] [Poster]

   Introduction: Patients with IBD often present with abdominal pain and diarrhea. However, distinguishing between active IBD, acute enteric infection, or the coexistence of both, can be difficult. It is unknown whether enteric infection may be a manifestation of active disease in patients with IBD, and only a few studies have evaluated endoscopic findings in symptomatic IBD patients with a positive stool PCR. Our aim was to assess whether enteric infections in IBD patients are associated with disease activity.Methods: A retrospective observational cohort analysis of IBD patients with Crohn’s disease, ulcerative colitis or indeterminate colitis seen at HMH IBD Center from 2015 to 2020 who had stool PCR testing for diarrhea was performed. Data was collected on demographics including age, sex, disease subtype, disease location and endoscopic findings within 3 months of stool PCR. Patients without endoscopic findings within 3 months were excluded. Endoscopic scoring was converted to remission, mild, moderate or severe based on the Mayo endoscopic score or Rutgeert’s score and/or Crohn’s Disease Simple Endoscopic score. Results: There were 193 patients who had at least one stool PCR test for a total of 258 stool PCRs. Among these, an enteric infection was identified in 95(49.22%) of patients and 138(53.49%) of the PCR tests. Patients with an enteric infection were significantly less likely to have CD, 62 (44.93%) compared to 77 (64.1%) those without infection, (p=0.0077) (Table 1). There was a significant difference in endoscopic findings at three months with and without enteric infection (p=.017). Patients with disease located in either colon or small bowel alone were significantly associated with a positive stool PCR. An elevated lactoferrin was significantly associated with a positive stool PCR (p =0.02), but was not significant for an elevated fecal calprotectin. The most common infection identified was Clostridioides difficile in 65 (46.43%) followed by Enteropathogenic Escherichia Coli 19 (13.57%) (Table 2). Discussion: IBD patients in our study population showed that UC more than CD, those with colonic or small bowel disease alone, and having higher endoscopic severity within 3 months of testing, were more likely to have stool PCR positive for enteric infection, most commonly Clostridioides difficile and Escherichia coli. Our study shows that achieving endoscopic remission especially in those with UC or colonic disease can reduce the likelihood of enteric infections in our IBD patients.

2019

1. Beating Heart Model for Surgical Simulation Saleh, Adam, Beckerman, Z. Fraser, C. Dell Medical School Symposium, September 2019

2016

1. Test Isolation of Wharton’s Jelly and Evaluation of In Situ Osteogenic Differentiation Potential of Wharton’s Jelly-Embedded Stem Cells Saleh, Adam, Triolo, F. McGovern Student Abstracts, July 2016 [Abs] [HTML] [PDF]

   Introduction: Wharton’s jelly-derived mesenchymal stem cells (WJMSC) are considered to be a promising new source for regenerative medicine. They are derived from wharton’s jelly, which is a gelatinous tissue located in the umbilical cord. It combines the benefits of adult stem cells and embryonic stem cells while avoiding the ethical and physical limitations of both. Specifically, WJMSCs have anti-tumoral properties and are immunosuppressant. Addtionally, WJMSC come with it’s own natural tissue construct, the wharton’s jelly itself which is loaded with rich extra-cellular matrices and proteins that aid in the growth and development of WJMSCs in vivo and in vitro. Collectively, these properties are exciting for regenerative medicine and warrant investigation in order to further explore potential clinical applications of WJMSCs. Specifically within the lab of Dr. Triolo, WJMSC are currently being used in pioneering experiments to treat cleft palate in infants. In order to use the mesenchymal stem cells found within the wharton’s jelly for the treatment of cleft palate , the wharton’s jelly must first be isolated from the umbilical cord and the osteogenic differentiation potential of the WJMSC muse then be evaluated.Methods: The wharton’s jelly was isolated through a set protocol in which the umbilical cord is cleaned and divided into pieces of roughly 5-8 cm in length. The pieces were cleaned and opened, then the three vessels innate to the umbilical cord were removed. The wharton’s jelly was then scraped off the epithelial tissue and placed in phosphate buffer solution. The isolated Wharton’s jelly was then placed in both an osteogenic media and a control media and observed for mineralization after fourteen days using alizarin red staining. Results: The isolation method for wharton’s jelly from the umbilical cord was proven effective by the results of the wharton’s jelly in culture. After fourteen days, the plates containing wharton’s jelly within osteogenic media showed significant mineralization as indicated by the alizarin red staining. This was further verified by comparing the mineralization of the WJMSC in the osteogenic media with the WJMSC in the control media which showed no mineralization. Conclusions: The results of this experiment reinforced the promising nature of WJMSC in clinical applications. The WJMSC showed strong differentiation potency in situ when placed in osteogenic media, showing clear signs of differentiation by its mineral deposits just after fourteen days. These results reinforce the ability of WJMSC to differentiate osteogenically and be used in clinical applications such as the treatment of cleft palate.