About

James D. Lewis, MD, MSCE, is a Professor of Medicine (Gastroenterology) at the University of Pennsylvania Perelman School of Medicine. He is also a Senior Fellow at the Leonard Davis Institute of Health Economics and a Senior Scholar at the Center for Clinical Epidemiology and Biostatistics at the same institution. Dr. Lewis specializes in epidemiology and clinical research related to inflammatory bowel disease (IBD), colon cancer, and gastroenterology. His research focuses on understanding the epidemiology, clinical management, and treatment outcomes of IBD and related gastrointestinal conditions. He has held multiple leadership roles, including Director of the Clinic Epidemiology T32 Training Program, Director of the Gastroenterology and Hepatology Clinical Research Program, and Co-Director of the Biomedical Data Science Core of the Center for Molecular Studies in Digestive and Liver Diseases. Dr. Lewis's work involves extensive clinical and epidemiological research, contributing significantly to the understanding of disease mechanisms, treatment strategies, and health economics in gastroenterology.

Research topics

• Internal medicine
• Medicine
• Biology
• Gastroenterology
• Surgery
• Cardiology
• Demography
• Chemistry
• Genetics
• Computational biology
• Family medicine
• Biochemistry
• Microbiology

Selected publications

• Spatial transcriptomics atlas of inflammatory bowel disease to guide implementation in research consortiums and clinical trials

  Nature Communications · 2026-04-28

  articleOpen access

  Using over 100 intestinal tissue sections from non-diseased controls and patients with ulcerative colitis or Crohn's disease across multiple inflammatory bowel disease consortia, we construct a spatially resolved atlas containing over three million cells and systematically evaluate two imaging-based spatial transcriptomics platforms. Here we show that CosMx tends to achieve higher detection efficiency than Xenium across commercially available panels in both ulcerative colitis and Crohn's disease, whereas Xenium shows reduced performance associated with tissue type, block quality, and panel size. CosMx identifies regulatory T cell associated biology in both disease subtypes, which we validate using independent laboratory experiments and multi-plex spatial multi-omics. CosMx's data quality remains stable across variation in fixation time and sectioning procedures, supporting its operational feasibility for multi-center studies. This study establishes a technical and biological benchmark for the application of single-cell-resolved spatial transcriptomics in gastrointestinal tissue, enabling more reliable application of spatial technologies in translational inflammatory bowel disease research.

  PublisherDOI

• S920 Diagnostic Codes Performance for Identification of Eosinophilic Gastrointestinal Diseases Varies by Reference Standard Definition and Disease Subtype

  The American Journal of Gastroenterology · 2025-10-01

  articleSenior author

  Introduction: Eosinophilic gastrointestinal diseases (EGIDs) are understudied. Internal Classification of Diseases (ICD) codes are a potential tool to facilitate EGID research, but their accuracy is unknown. We aimed to evaluate the ICD performance metrics for identifying EGIDs using multiple case definitions and across subtypes. Methods: We identified GI pathology reports containing “eosinophil” and paired them with preceding clinic notes from a large health system. Reference standard diagnoses were assigned via chart review and compared to ICD codes. The EoE reference standard required positive histology with variable definitions of esophageal dysfunction and diagnostic history. Defining reference standard for eosinophilic gastritis (EoG) and eosinophilic enteritis (EoN) included liberal (any eosinophils plus symptoms) and restrictive (increased eosinophils plus symptoms) criteria; only liberal criteria were used for eosinophilic colitis (EoC) due to limited detail. For non-EoE EGIDs, a rule-based natural language processing approach captured numeric or descriptive eosinophil increases. EoG and EoN, lacking distinct ICD codes, were evaluated individually and combined under the eosinophilic gastroenteritis code. Performance metrics included sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, Cohen’s kappa, and F1 score (harmonic mean of precision and recall). Results: Defining EoE reference standard with symptoms of dysphagia and food impaction only, the ICD achieved an F1 score of 0.70 (95% confidence interval [CI] 0.59-0.80), with a PPV of 0.64 and sensitivity of 0.77. Including additional esophageal dysfunction symptoms yielded a modest improvement in F1 score (ΔF1 = 0.02; 95% CI 0.0 to 0.08). Further addition of history of EoE documented in note free text resulted in higher PPV (0.95), specificity (0.98), and F1 score (0.84; 95% CI 0.78-0.90), with similar sensitivity (0.76). The diagnostic performance of ICD codes for identifying EoG or EoN demonstrated low PPV (0.17-0.33) and sensitivity (0.08-0.33) across individual subtypes and in combination, with slightly better performance for restrictive definitions. No patients with EoC received the corresponding ICD code, resulting in zero sensitivity and undefined PPV. Conclusion: The diagnostic performance of ICD codes for EoE is influenced by the specific criteria and clinical data elements incorporated in the reference standard definition. The ICD codes for non-EoE EGIDs demonstrate high false positive and false negative rates. These findings highlight the need for improved case identification methods to facilitate EGID research.

  PublisherDOI

• Relationship Between Timing of Hemodialysis and Procedure-Related Complications Following Endoscopy in Patients with End-Stage Renal Disease

  Digestive Diseases and Sciences · 2025-06-18 · 2 citations

  articleOpen access

  PURPOSE: There is a growing population of patients with end-stage renal disease (ESRD) on hemodialysis (HD) requiring endoscopic procedures. While literature supports timing general surgeries one day following dialysis, there is inadequate data on optimal timing of endoscopic procedures. This study examined the procedural complications related to endoscopic procedures based on timing post-HD. METHODS: This retrospective cohort study included endoscopic procedures in patients with ESRD on thrice-weekly HD at a single institution. Procedural complications were analyzed using a GEE model incorporating inverse probability treatment weighting logistic regression based on pre-procedural covariates (Model 1) and combined pre- and intra-procedural covariates (Model 2). RESULTS: 252 procedures were identified in 191 unique patients, among which 48, 147 and 57 were performed 0, 1 and 2 days post-HD, respectively. Procedures performed on the same day post-HD were more likely to be inpatient (n = 44, 91.7% vs. n = 101, 68.7% vs. n = 39, 68.4% for 0 vs. 1 vs. 2 days post-HD, respectively; p = 0.005) with indication for GI bleeding and/or anemia (n = 40, 83.3% vs. n = 95, 64.6% vs. n = 42, 73.7% for 0 vs. 1 vs. 2 days post-HD, respectively; p = 0.04). Patients undergoing procedures 0 compared to 1-2 days post-HD were more likely to experience mortality (Model 1 OR 2.91, 95% CI 1.24-6.80; p = 0.01; Model 2 OR 3.22, 95% CI 1.42-7.29, p = 0.005). CONCLUSION: Endoscopic procedures performed on the same day following HD may be associated with a higher risk for mortality. Further studies are needed to reproduce these findings and explore the underlying mechanisms driving this association.

  PublisherOA PDFDOI

• A Longitudinal Post-authorization Safety Study of Golimumab in Treatment of Ulcerative Colitis: A Cohort Study in Denmark and Sweden, 2013–2021

  Drug Safety · 2025-02-06 · 1 citations

  articleOpen access

  BACKGROUND: When golimumab (GLM) was approved for the treatment of moderate to severe ulcerative colitis (UC) in 2013, a post-authorization safety study was conducted. OBJECTIVE: Our objective was to examine whether exposure to GLM was associated with an increased incidence of all-cause total colectomy, colorectal cancer, and hepatosplenic T-cell lymphoma in Denmark and Sweden. METHODS: We conducted a new-user, active comparator cohort study of patients with UC in 2013-2021. Exposure to GLM, other anti-tumor necrosis factor (TNF) agents (infliximab and adalimumab) and thiopurines was a time-varying variable. Therapies were based on prescription redemptions and hospital-based administration of medications from national prescription and hospital registers. The association between exposure to study therapies and outcomes was evaluated using Poisson regression of incidence rates (IRs), presented as IR ratios (IRRs) and 95% confidence intervals (CIs). RESULTS: A total of 5177 and 7469 patients were included in Denmark and Sweden, respectively. The IR of all-cause total colectomy per 1000 person-years was higher in Denmark (IR 42.6; 95% CI 38.9-46.2) than in Sweden (IR 16.1; 95% CI 14.2-18.0). No significant difference was observed in all-cause total colectomy between GLM and other anti-TNF agents (Denmark: adjusted IRR [aIRR] 1.28; 95% CI 0.98-1.66; Sweden: aIRR 1.17; 95% CI 0.72-1.90). A significant difference was observed between GLM and thiopurines (Denmark: aIRR 13.62; 95% CI 8.73-21.26; Sweden: aIRR 4.52; 2.75-7.41). Privacy regulations prevented analysis of a few colorectal cancer events. No hepatosplenic T-cell lymphoma events were identified. CONCLUSION: The IR of all-cause total colectomy with GLM was similar to that with other anti-TNF agents but was much higher than with thiopurines, probably related to confounding by indication.

  PublisherOA PDFDOI

• How to Process News About Ultra Processed Food

  Clinical Gastroenterology and Hepatology · 2025-12-06

  editorial1st authorCorresponding
  PublisherDOI

• Mo1937: THE NEED FOR TOOLS TO TRIAGE USE OF ABDOMINAL CT IMAGING IN THE EVALUATION OF CROHN’S DISEASE IN THE EMERGENCY DEPARTMENT

  Gastroenterology · 2025-05-01

  articleSenior author
  PublisherDOI

• 405 Performance Errors in Hyperangulated Video Laryngoscopy

  Annals of Emergency Medicine · 2025-08-22

  articleOpen access
  PublisherOA PDFDOI

• Safety and Clinical Effectiveness of GLP1 Receptor Agonists in Inflammatory Bowel Disease Patients

  Clinical Gastroenterology and Hepatology · 2025-01-30 · 9 citations

  article
  PublisherDOI

• Inflammatory Bowel Diseases-Specific Cognitive Behavioral Therapy Delivered Through Telehealth Reduces Disability: Addressing Disability Effectively With Psychosocial Telemedicine Pragmatic Randomized Controlled Trial

  The American Journal of Gastroenterology · 2025-07-30 · 6 citations

  article

  INTRODUCTION: Inflammatory bowel disease (IBD)-related disability encompasses physical and psychosocial dimensions, and it is under-recognized and under-treated in patients with IBD. Cognitive behavioral therapy (CBT) is a structured, time-limited, and problem-focused psychotherapy that targets inaccurate thoughts and maladaptive behaviors. We aimed to investigate the effect of IBD-specific CBT delivered through telehealth on disability in patients with IBD. METHODS: "Addressing Disability Effectively with Psychosocial Telemedicine" (NCT05635292) was an open-label, multicenter 1:2 randomized controlled trial for adults with moderate-to-severe IBD-related disability (assessed by the IBD Disability Index [IBD-DI]) to receive 8 weeks of telehealth-delivered CBT or usual care. Recruitment occurred between February and October 2023 at 5 gastroenterology clinics in the United States participating in the Crohn's & Colitis Foundation's Clinical Research Alliance. Clinical, demographic, disease activity, and psychological data were collected at baseline and at week 8. The primary end point was changes in IBD-DI (absolute change in IBD-DI score; clinically relevant improvement of 17-point decrease in IBD-DI), adjusted for IBD subtype and disease activity. The secondary outcomes were differences in direct and indirect costs between groups. Changes in IBD clinical disease activity was an exploratory end point. RESULTS: Ninety patients were randomized (74.4% Crohn's disease; 25.6% ulcerative colitis; 76.7% clinically active), of which 74 (82.2%) completed the trial and 69 (76.6%) adhered to the 8-week teletherapy protocol. Teletherapy group had significantly reduced disability (β = 5.9, P = 0.02) and clinically relevant improvements (adjusted odds ratio 2.9, 95% confidence interval 1.0-8.2 P = 0.04) compared with controls. Clinical disease activity and the cost of IBD (both direct and indirect) did not differ between the 2 groups. DISCUSSION: In a randomized controlled trial of patients with IBD, an 8-week telehealth-delivered IBD-specific CBT protocol reduced IBD-related disability, independent of clinical disease activity.

  PublisherDOI

• Distinguishing diet- and microbe-derived metabolites in the human gut

  Microbiome · 2025-10-16 · 2 citations

  articleOpen access

  BACKGROUND: Human gut microbes metabolize food and host secretions, consuming and producing small molecules that are important to health and homeostasis. Here, we present an atlas of diet- and microbiome-derived metabolites in the human gut, constructed from a controlled feeding experiment of adults on omnivore and enteral nutrition diets. RESULTS: By comparing metabolite concentration before and after microbiome depletion with antibiotics and polyethylene glycol, we identified 2856 microbial products decreasing and 1057 microbial substrates increasing in concentration after depletion. We also identified 2496 diet-derived metabolites by comparing diet groups when the microbiome was depleted. Seven days after antibiotics, 98% of gut metabolites recovered to pre-antibiotic levels in the omnivore group. In plasma samples, only 93 microbiome-derived metabolites varied with gut microbiome depletion, indicating a limited impact on circulating metabolites. To demonstrate our metabolite atlas, we annotated metabolites associated with inflammatory bowel disease and identified the microbiome-derived metabolites altered in gut dysbiosis. CONCLUSIONS: We identified metabolites associated with the metabolism of the human gut microbiome, mapping its overall metabolic potential. Furthermore, we measured the rate at which metabolites were recovered following gut microbiome disruption.

  PublisherOA PDFDOI

Recent grants

• NIH Grant R03DK056729

  NIH · $144k · 2003

• NIH Grant R01CA102599

  NIH · $1.5M · 2009

• Clinical Epidemiology Training in Gastroenterology

  NIH · $9.2M · 1997–2027

• NIH Grant R01DK059961

  NIH · $3.2M · 2008

• NIH Grant K08DK002589

  NIH · $629k · 2004

Frequent coauthors

• Meenakshi Bewtra

  University of Pennsylvania

  147 shared

• Sumona Saha

  UW Health University Hospital

  109 shared

• Gary R. Lichtenstein

  103 shared

• David Hudesman

  102 shared

• Gary D. Wu

  University of Pennsylvania

  101 shared

• Colleen M. Brensinger

  University of Pennsylvania

  82 shared

• Frank I. Scott

  University of Colorado Boulder

  80 shared

• Themistocles Dassopoulos

  Wockhardt (United States)

  72 shared

Labs

• James D. Lewis LabPI