publications

2024

1. Factors Correlated With Transmural Healing In Patients With Crohn’s Disease In Long-Term Clinical Remission On Anti-TNF Medication Maconi, G., Lepore, F., Saleh, Adam, Saibeni, S., Bezzio, C., Cheli, S., Massari, A., Gridavilla, D., Ferretti, F., Cannatelli, R., Ardizzone, S., Clementi, E., Abraham, B. Digestive and Liver Disease, June 2024 [Abs] [DOI]

   Background & aims Transmural healing is a long-term target for patients with Crohn's disease. Factors contributing to its promotion are poorly understood. This study assessed factors correlating with transmural healing based on intestinal ultrasound, in patients in long-term clinical remission on anti-TNF. Methods 68 consecutive Crohn's patients on adalimumab (50) or infliximab (18) therapy with clinical remission ≥1 year were recruited and assessed for clinical features, trough serum levels of anti-TNF and intestinal ultrasound findings. Univariate analysis and multivariate binary logistic regression analysis identified variables independently associated with bowel wall thickening behavior. Results Sixty eight patients were in remission for a mean of 4.1 years. Thirty-six patients (52.9 %) showed anti-TNF trough levels below the normal threshold. Twenty-two patients (38.4 %) showed transmural healing, 32 (47.1 %) transmural response, and 26 (38.2 %) no treatment response. Transmural healing correlated with higher BMI and lower baseline bowel wall thickening; transmural response correlated with short Crohn's disease duration, high drug levels, and with non-stricturing phenotype. Treatment non-response correlated with lower BMI, lower drug levels, higher baseline bowel wall thickening, and stricturing phenotype. Conclusions Lack of transmural healing in stable remission Crohn's patients on anti-TNF therapy is multifactorial, mainly due to low anti-TNFs trough levels, development of strictures, and higher baseline bowel wall thickening at treatment initiation.

1. Postoperative Ustekinumab Drug Levels and Disease Activity in Patients with Crohn’s Disease Moskow, J., Thurston, T., Saleh, Adam, Shah, A., Abraham, B. Glassner, K., Digestive Diseases and Sciences, May 2024 [Abs] [DOI]

   Aims This study investigated how post-operative ustekinumab levels relate to surgery type, endoscopic, biochemical, and clinical outcomes in patients with Crohn’s Disease. Methods A retrospective study of patients with Crohn’s Disease with a disease-related operation between 2016 and 2022 assessed outcomes based on ustekinumab levels. Patients were included if they had an ustekinumab trough level within two years post-operatively. Patients were separated into groups based on whether their ustekinumab trough levels were adequate, defined as ≥ 4 μg/mL, or suboptimal < 4 μg/mL. A subset of patients with ustekinumab levels taken within two years both before and after surgery was compared to non-surgical treatment-escalated controls outside the initial patient set. Harvey-Bradshaw index was used to evaluate clinical disease activity. Rutgeert’s and Simple Endoscopic Score for Crohn’s Disease was used to evaluate endoscopic disease activity. C-reactive protein and fecal calprotectin values were collected to evaluate the molecular inflammatory disease state. CBC data were used to evaluate anemia. Results Forty-four patients were identified, which had ustekinumab levels after Crohn’s Disease-related surgery. Twelve of these patients had pre-operative levels and were compared to 26 non-surgical treatment-escalated controls. No relationship between ustekinumab levels and endoscopic or clinical disease activity post-operatively was found. This also held true when looking at different surgery types. Adequate levels of ustekinumab post-operatively yielded lower risk of anemia. Surgery itself did not have an impact on ustekinumab levels. Conclusions This study provided new insights into how post-operative ustekinumab levels impact several factors in patients having undergone Crohn’s disease-related surgery.

1. Measurement and Application of Incidentally Detected Coronary Calcium: JACC Review Topic of the Week Parsa, S., Saleh, Adam, Raygor, V., Hoeting, N., Rao, A., Navar, A.M., Rohatgi, A., Kay, F., Abbara, S., Khera, A., Joshi, P. Journal of the American College of Cardiology, April 2024 [Abs] [DOI]

   Coronary artery calcium (CAC) scoring is a powerful tool for atherosclerotic cardiovascular disease risk stratification. The nongated, noncontrast chest computed tomography scan (NCCT) has emerged as a source of CAC characterization with tremendous potential due to the high volume of NCCT scans. Application of incidental CAC characterization from NCCT has raised questions around score accuracy, standardization of methodology including the possibility of deep learning to automate the process, and the risk stratification potential of an NCCT-derived score. In this review, the authors aim to summarize the role of NCCT-derived CAC in preventive cardiovascular health today as well as explore future avenues for eventual clinical applicability in specific patient populations and broader health systems.

1. Therapeutic drug monitoring in patients with inflammatory bowel disease on ustekinumab Saleh, Adam, Stading, R., Miroballi, N., Glassner, K., Abraham, B. Journal of Digestive Diseases, April 2024 [Abs] [DOI]

   Objective Therapeutic drug monitoring is used clinically to guide anti-tumor necrosis factor (TNF) therapy for inflammatory bowel disease (IBD), but its use for ustekinumab (UST) remains unclear. This study aimed to determine predictive variables of UST levels. Methods In this retrospective cohort of patients with IBD, UST trough levels were drawn at maintenance dosing. Relationships between UST trough levels and demographics, therapy, and outcomes were analyzed. Machine-learning models were used to infer combinatorial traits predictive of UST levels. Results Altogether 177 patients with IBD on UST had a mean UST trough level of 4.742 μg/mL. The injection schedule correlated significantly (P < 0.001) with UST levels. Naiveté to anti-TNFs correlated with higher UST levels (P = 0.048). Univariate analysis revealed that higher inflammatory biomarkers significantly correlated to lower UST levels and a lower Simple Endoscopic Score to Crohn's Disease to adequate UST levels (P = 0.018). Multivariate analysis identified body mass index (BMI), previous anti-TNF failure, and laboratory flare as predictors of UST levels with an area under the receiver operating characteristic curve (AUROC) of 0.72. The UST cut-off level of 5.77 μg/mL yielded a 0.79 AUROC, 80% sensitivity, and 81% specificity for predicting endoscopic remission of Crohn's disease. For the clinical remission end-point in ulcerative colitis, UST level of 4.73 μg/mL yielded a 0.69 AUROC, 53% sensitivity, and 86% specificity. Conclusions Higher UST levels correlated with less disease activity. BMI was an important consideration for UST response as well. Therefore, UST dose adjustments to reach target levels may optimize response.

1. Therapeutic drug monitoring in inflammatory bowel disease patients on vedolizumab Ansari, M., Glassner, K., Irani, M., Saleh, Adam, Wang, L., Ezeana, C., Wong, S., Perry, C., Abraham, B. Journal of Digestive Diseases, April 2024 [Abs] [DOI]

   Objective We aimed to investigate whether vedolizumab (VDZ) levels were associated with inflammatory markers or clinical or endoscopic scoring in inflammatory bowel disease (IBD). Methods: Besides demographic data, clinical scoring, endoscopic data, and laboratory markers of IBD patients treated with VDZ from 2015 to 2020 who had trough levels drawn on maintenance therapy were collected at baseline and at follow-up (after at least 8 weeks on VDZ therapy or after change in dose frequency). Low drug levels were defined as VDZ trough <20 μg/mL.Results: We identified 89 patients with a mean age of 42.9 years. Of the 90 total trough levels drawn, 61.1% were low. Among patients on every 8 week (Q8 week) VDZ dosing, 81.5% had low troughs. After increasing dosing frequency to Q4 weeks, all patients showed improvement in VDZ levels, but 30.6% remained <20 μg/mL. Higher VDZ levels on Q8 week dosing were associated with higher albumin levels (P = 0.01). While higher VDZ levels on Q4 week dosing were associated with higher albumin (P = 0.02), lower erythrocyte sedimentation rate (P = 0.04) and higher likelihood of having mild disease or endoscopic remission (P = 0.01). No significant association was found between VDZ levels and clinical scoring, body mass index, hemoglobin, vitamin D or platelet levels on either Q8 or Q4 week dosing. Conclusions: Higher VDZ troughs were associated with higher albumin, mild endoscopic disease or endoscopic remission. Patients who continue to have low VDZ troughs despite Q4 week dosing may require a change in therapy.

2023

1. Association of enteric infections and disease activity in inflammatory bowel disease: a retrospective study utilizing machine learning techniques Kim, C., Maturi, V., Saleh, Adam, Garza, M., Narwankar, M., Perry, C., Glassner, K., Abraham, B. American Journal of Digestive Diseases, December 2023 [Abs] [DOI]

   Enteric infections are frequently encountered in patients with active IBD symptoms. Few studies have evaluated endoscopic findings in symptomatic IBD patients with an enteric infection. We hypothesized that IBD patients with an enteric infection were more likely to have active inflammation on colonoscopy. Machine learning techniques were used to predict the presence of enteric infection in IBD patients with active disease on colonoscopy. Patients with IBD seen from 2015 to 2020 at Houston Methodist Inflammatory Bowel Disease program were identified. Those who had stool PCR testing performed for evaluation of diarrhea were included in the study. Retrospective data collection included demographic data, disease subtype, disease location, laboratory data, clinical and endoscopic findings. Machine learning techniques were used to help identify predictors of the presence of an enteric infection. There were 284 patients with at least one stool PCR test and among these, 167 (58.8%) patients had an infection identified. Those with ulcerative colitis (UC), particularly pancolitis, were more likely to have an infection than those with Crohn’s disease (CD). Both UC and CD patients with inflammation identified on colonoscopy (based on endoscopic score) were more likely to have an enteric infection. Finally, a multivariate analysis using machine learning techniques showed that age predicted likelihood of enteric infection in IBD patients. Enteric infections were commonly identified in IBD patients being evaluated for diarrhea. Clostridioides difficile and Escherichia coli species were most common. UC, particularly pancolitis, and endoscopic disease severity increased the likelihood of enteric infection. Age was also a significant predictor as shown in our multivariate analysis. Further tailoring of machine learning techniques with larger patient numbers and additional variables are future research areas of interest.

1. Utility of Intestinal Ultrasound in Clinical Decision-Making for Inflammatory Bowel Disease Saleh, Adam, Abraham, B. Crohn's & Colitis 360, May 2023 [Abs] [DOI]

   Background: There is a clinical need to improve monitoring of inflammatory bowel disease (IBD) disease activity. Despite being used regularly in European countries, intestinal ultrasound (IUS) has been implemented less in the United States for unclear reasons. Aims: The aim of this study is to illustrate how IUS can be used as a clinical decision-making tool in an American IBD cohort. Methods: This retrospective cohort analysis evaluated patients with IBD seen at our institution who underwent IUS as part of routine evaluation of their IBD from July 2020 to March 2022. To evaluate the clinical utility of IUS for different patient populations and against more frequently used measures of inflammation, we compared patient demographics, inflammatory markers, clinical scores, and medications between patients in remission and those with active inflammation. Treatment plans between the two groups were compared and we analyzed patients with follow-up IUS visits to validate treatment plan decisions at initial evaluation. Results: Out of 148 total patients with IUS, we found that 62.1% (N=92) of our patients had active disease and 37.9% (N=56) were in remission. UCAI and Mayo scores were both significantly correlated with IUS findings. The treatment plan was significantly correlated with IUS findings (p=0.004). At follow-up, we observed an overall decrease in intestinal thickening, improvements in vascular flow, and mural stratification. Conclusion: Clinical decisions incorporating IUS findings effectively reduced inflammation in our IBD patients. IUS should be strongly considered by IBD clinicians in the United States for monitoring disease activity in IBD.

1. Integrating Intestinal Ultrasound into an Inflammatory Bowel Disease Practice: How to Get Started Abraham, B. Reddy, Dheeraj, Saleh, Adam Crohn's & Colitis 360, August 2023 [Abs] [DOI]

   Intestinal ultrasound (IUS) offers a safe, noninvasive, point-of-care tool for diagnosing and monitoring disease activity in patients with inflammatory bowel disease (IBD). IUS is used widely in Europe and Canada for IBD, but it remains underutilized in the United States. Growing interest in IUS in the United States has prompted many IBD centers to train their faculty in IUS. This, however, raises questions about how to effectively use this new tool in the United States, which does not use a social medicine model like those implemented in Europe and Canada. Here, we provide a practical framework for incorporating IUS in an IBD practice in the United States, including training requirements, equipment, and protocols for implementing IUS in daily practice.

1. The Role of Fecal Microbiota Transplantation in the Induction of Remission in Ulcerative Colitis Saleh, Adam, Parsa, S., Garza, M., Quigley, E.M.M., Abraham, B. Digestive Diseases, March 2023 [Abs] [DOI]

   Background: Considerable research supports an important role for the microbiome and/or microbiome–host immune system interactions in the pathogenesis of inflammatory bowel disease (IBD). Consequently, microbiota-modulating interventions, such as fecal microbiota transplantation (FMT), have attracted interest in the management of IBD, including ulcerative colitis (UC). Summary: While the clinical response to FMT in UC has varied between different studies, results to date may offer guidance towards optimal use of FMT. Thus, increased microbiome biodiversity, the presence of short-chain fatty acid producing bacteria, Clostridium Cluster IV and XIVa, Odoribacter splanchnicus and reduced levels of Caudovirales bacteriophages have been identified as characteristics of the donor microbiome that predict a positive response. However, inconsistency in FMT protocol between studies confounds their interpretation, so it is currently difficult to predict response and premature to recommend FMT, in general, as a treatment for UC. Additional randomized controlled trials designed based on previous findings and employing a standardized protocol are needed to define the role of FMT in the management of UC. Key Messages: There is a well-developed rationale for the use of microbiome-modulating interventions in UC. Despite variations in study protocol and limitations in study design that confound their interpretation, FMT seems to benefit patients with UC, overall. Available data identify factors predicting FMT response and should lead to the development of optimal FMT study protocols.

1. Look What the Cat Dragged in! Recurrent Clostridioides difficile from a Household Cat Garza, M., Braden, T., Saleh, Adam, Nabbout, L., Quigley, E.M.M., Mathur, N. American Journal of Case Reports, September 2023 [Abs] [DOI]

   BACKGROUND: Clostridioides difficile (C. difficile) is a bacterium that is well known for causing serious diarrheal infections and can even lead to colon cancer if left untreated. Disruption of the normal healthy bacteria in the colon can lead to development of C. difficile colitis. Risk factors for C. difficile infections (CDI) include recent antibiotic exposure, hospital or nursing home stays, inflammatory bowel disease (IBD), or impaired immunity. There is an increasing incidence of community-associated CDI (CA-CDI) in individuals without the common risk factors, which has implicated natural reservoirs, zoonoses, originating from animals such as domestic cats and dogs, livestock, shellfish, and wild animals. CASE REPORT: A previously healthy 31-year-old woman with recurrent CA-CDI suspected to be acquired from a household cat represents a novel presentation. The patient had an initial case of severe diarrhea following recent antibiotic exposure, was briefly monitored in hospital, and was diagnosed with CDI. She was trialed on oral vancomycin, which resulted in temporary resolution of her symptoms. Her symptoms recurred, however, and did not improve despite treatment with multiple therapeutic options over a period of months. Ultimately, the patient was not able to achieve long-term resolution of her symptoms until her newly adopted pet cat was treated by a veterinarian. CONCLUSIONS: In conclusion, this case report explores the epidemiologic risk factors of zoonotic CA-CDI and the importance of early identification, evaluation, and prevention of disease. This case demonstrates the significance of thorough history taking, contact (pet) tracing, and proper treatment of recurrent CA-CDI.

2022

1. Biological Therapies for the Management of Enteric Disease: Considerations for the Clinician Saleh, Adam, Ansari, U., Abughazaleh, S., Glassner, K., Abraham, B. Biologics: Targets and Therapy, June 2022 [Abs] [DOI]

   Several biologic therapies have been approved for enteric diseases. We evaluate each biologic’s role based on their mechanism of action in treating these conditions. This review examines data on efficacy and safety, as well as considerations for using these therapies in clinical practice in inflammatory bowel diseases, enteric infections—specifically Clostridioides difficile colitis—and potentially in the increasingly prevalent disorder of eosinophilic esophagitis. When choosing an appropriate therapy, it is important to assess patient severity, as most biologics are approved for those with moderate to severe disease activity. With many years of data from clinical trials and real-world experience, these therapies have been shown to improve outcomes overall in enteric diseases, contributing to more options for our patients.