Chiraag V Kulkarni

All Publications

• Statin use is associated with protection against acute cholangitis in patients with primary sclerosing cholangitis: a multi-center retrospective cohort study. Clinical and translational gastroenterology Kulkarni, C., Cholankeril, G., Fardeen, T., Rathkey, J., Khan, S., Murag, S., Lerrigo, R., Kamal, A., Mannalithara, A., Jalal, P., Ahmed, A., Vierling, J., Goel, A., Sinha, S. R. 2025

  Abstract

  Patients with primary sclerosing cholangitis (PSC) are at increased risk for acute cholangitis. The epidemiological risks for cholangitis are poorly studied despite the high morbidity associated with this infection. This study's aim was to understand the impact of statins on acute cholangitis in PSC.This multicenter, retrospective cohort study assessed data from 294 patients with PSC at Stanford Medical Center, Baylor Medical Center, and Valley Medical Center. Clinical factors associated with development of cholangitis were identified using multivariable Cox regression.The patients were predominantly male (68.7%) with a median age at enrollment of 48 years [IQR: 31.0-60.8]. Fifty patients (17.0%) were prescribed statins. Median follow-up time was 6 years [IQR: 2.0-12.0], in which 29.6% (n=87) developed cholangitis.In multivariable analysis, statins were associated with an 81% reduction in cholangitis (HR 0.19, 95% CI 0.03-0.64). Statins were associated with a lower incidence of cholangitis at 36 months compared with patients not on statin therapy (incidence of 11.9% vs 34.7%, p<0.001). Statins were also associated with increased time-to-stricture (p=0.004), an outcome known to be associated with PSC complications1,2.Statin therapy is associated with reduced risk of cholangitis in PSC, possibly by delaying time to development of a dominant or high-grade strictures. In patients with PSC, use of statin therapy may be a beneficial modality to prevent the development of cholangitis and warrants further investigation.

  View details for DOI 10.14309/ctg.0000000000000816

  View details for PubMedID 39835681

• Artificial intelligence and machine learning technologies in ulcerative colitis. Therapeutic advances in gastroenterology Kulkarni, C., Liu, D., Fardeen, T., Dickson, E. R., Jang, H., Sinha, S. R., Gubatan, J. 2024; 17: 17562848241272001

  Abstract

  Interest in artificial intelligence (AI) applications for ulcerative colitis (UC) has grown tremendously in recent years. In the past 5 years, there have been over 80 studies focused on machine learning (ML) tools to address a wide range of clinical problems in UC, including diagnosis, prognosis, identification of new UC biomarkers, monitoring of disease activity, and prediction of complications. AI classifiers such as random forest, support vector machines, neural networks, and logistic regression models have been used to model UC clinical outcomes using molecular (transcriptomic) and clinical (electronic health record and laboratory) datasets with relatively high performance (accuracy, sensitivity, and specificity). Application of ML algorithms such as computer vision, guided image filtering, and convolutional neural networks have also been utilized to analyze large and high-dimensional imaging datasets such as endoscopic, histologic, and radiological images for UC diagnosis and prediction of complications (post-surgical complications, colorectal cancer). Incorporation of these ML tools to guide and optimize UC clinical practice is promising but will require large, high-quality validation studies that overcome the risk of bias as well as consider cost-effectiveness compared to standard of care.

  View details for DOI 10.1177/17562848241272001

  View details for PubMedID 39247718

  View details for PubMedCentralID PMC11378191

• Colonoscopy Prep Is Associated With Increased Risk of Flare Among Patients With Previously Inactive Inflammatory Bowel Disease Kulkarni, C., Talamantes, S. M., Sinha, S. LIPPINCOTT WILLIAMS & WILKINS. 2023: S840

  View details for Web of Science ID 001091849302218

• Oral Vancomycin Is Associated With Less IBD Therapy Intensification in PSC-IBD Talamantes, S. M., Kulkarni, C., Cholankeril, G., Fardeen, T., Sinha, S. LIPPINCOTT WILLIAMS & WILKINS. 2023: S830-S831

  View details for Web of Science ID 001091849302206

• Severe Diarrhea and Weight Loss Due to Protein-Losing Enteropathy: Don't Pass Up the PAS Stain. Digestive diseases and sciences Yeoh, A., Kulkarni, C., Ryan, E., Berry, G., Triadafilopoulos, G. 2023

  View details for DOI 10.1007/s10620-023-07982-6

  View details for PubMedID 37231192

• Dietary Exposures and Interventions in Inflammatory Bowel Disease: Current Evidence and Emerging Concepts. Nutrients Gubatan, J., Kulkarni, C. V., Talamantes, S. M., Temby, M., Fardeen, T., Sinha, S. R. 2023; 15 (3)

  Abstract

  Diet is intimately linked to the gastrointestinal (GI) tract and has potent effects on intestinal immune homeostasis. Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the GI tract. The therapeutic implications of diet in patients with IBD have received significant attention in recent years. In this review, we provide a contemporary and comprehensive overview of dietary exposures and interventions in IBD. Epidemiological studies suggest that ultra-processed foods, food additives, and emulsifiers are associated with a higher incidence of IBD. Exclusion and elimination diets are associated with improved symptoms in patients with IBD, but no effects on objective markers of inflammation. Specific dietary interventions (e.g., Mediterranean, specific carbohydrate, high fiber, ketogenic, anti-inflammatory diets) have been shown to reduce symptoms, improve inflammatory biomarkers, and quality of life metrics to varying degrees, but these studies are limited by study design, underpowering, heterogeneity, and confounding. To date, there is no robust evidence that any dietary intervention alone may replace standard therapies in patients with IBD. However, diet may play an adjunct role to induce or maintain clinical remission with standard IBD therapies. The results of novel dietary trials in IBD such as personalized fiber, intermittent fasting, and time-restricted diets are eagerly awaited.

  View details for DOI 10.3390/nu15030579

  View details for PubMedID 36771288

• Development and Validation of an Artificial Intelligence System to Optimize Clinician Review of Patient Records. JAMA network open Chi, E. A., Chi, G., Tsui, C. T., Jiang, Y., Jarr, K., Kulkarni, C. V., Zhang, M., Long, J., Ng, A. Y., Rajpurkar, P., Sinha, S. R. 2021; 4 (7): e2117391

  Abstract

  Importance: Physicians are required to work with rapidly growing amounts of medical data. Approximately 62% of time per patient is devoted to reviewing electronic health records (EHRs), with clinical data review being the most time-consuming portion.Objective: To determine whether an artificial intelligence (AI) system developed to organize and display new patient referral records would improve a clinician's ability to extract patient information compared with the current standard of care.Design, Setting, and Participants: In this prognostic study, an AI system was created to organize patient records and improve data retrieval. To evaluate the system on time and accuracy, a nonblinded, prospective study was conducted at a single academic medical center. Recruitment emails were sent to all physicians in the gastroenterology division, and 12 clinicians agreed to participate. Each of the clinicians participating in the study received 2 referral records: 1 AI-optimized patient record and 1 standard (non-AI-optimized) patient record. For each record, clinicians were asked 22 questions requiring them to search the assigned record for clinically relevant information. Clinicians reviewed records from June 1 to August 30, 2020.Main Outcomes and Measures: The time required to answer each question, along with accuracy, was measured for both records, with and without AI optimization. Participants were asked to assess overall satisfaction with the AI system, their preferred review method (AI-optimized vs standard), and other topics to assess clinical utility.Results: Twelve gastroenterology physicians/fellows completed the study. Compared with standard (non-AI-optimized) patient record review, the AI system saved first-time physician users 18% of the time used to answer the clinical questions (10.5 [95% CI, 8.5-12.6] vs 12.8 [95% CI, 9.4-16.2] minutes; P=.02). There was no significant decrease in accuracy when physicians retrieved important patient information (83.7% [95% CI, 79.3%-88.2%] with the AI-optimized vs 86.0% [95% CI, 81.8%-90.2%] without the AI-optimized record; P=.81). Survey responses from physicians were generally positive across all questions. Eleven of 12 physicians (92%) preferred the AI-optimized record review to standard review. Despite a learning curve pointed out by respondents, 11 of 12 physicians believed that the technology would save them time to assess new patient records and were interested in using this technology in their clinic.Conclusions and Relevance: In this prognostic study, an AI system helped physicians extract relevant patient information in a shorter time while maintaining high accuracy. This finding is particularly germane to the ever-increasing amounts of medical data and increased stressors on clinicians. Increased user familiarity with the AI system, along with further enhancements in the system itself, hold promise to further improve physician data extraction from large quantities of patient health records.

  View details for DOI 10.1001/jamanetworkopen.2021.17391

  View details for PubMedID 34297075

• Association of Anti-TNF Therapy With Increased Risk of Acute Cholangitis in Patients With Primary Sclerosing Cholangitis. Inflammatory bowel diseases Kulkarni, C., Murag, S., Cholankeril, G., Fardeen, T., Mannalithara, A., Lerrigo, R., Kamal, A., Ahmed, A., Goel, A., Sinha, S. R. 2020

  Abstract

  BACKGROUND: Patients with primary sclerosing cholangitis (PSC) are at increased risk of developing acute cholangitis. The majority of patients with PSC have comorbid inflammatory bowel disease, and many take immunosuppressive medications. The epidemiological risks for the development of acute cholangitis in patients with PSC, including the impact of immunosuppressive therapy, are unknown.METHODS: We conducted a 2-center, retrospective cohort study using data from 228 patients at Stanford University Medical Center and Santa Clara Valley Medical Center (CA), a county health care system. Patient demographics, medications, PSC disease severity, and inflammatory bowel disease status were extracted. Using stepwise variable selection, we included demographic and covariate predictors in the multiple logistic regression model assessing risk factors for cholangitis. Time-to-event analysis was performed to evaluate specific immunosuppressive medications and development of cholangitis.RESULTS: Thirty-one percent of patients had at least 1 episode of acute cholangitis (n = 72). Anti-tumor necrosis factor (TNF) therapy was associated with increased odds of acute cholangitis (odds ratio, 7.29; 95% confidence interval, 2.63-12.43), but immunomodulator use was protective against acute cholangitis (odds ratio, 0.23; 95% confidence interval, 0.05-0.76). Anti-TNF therapy was associated with decreased time-to-cholangitis, with a median time of 28.4 months; in contrast, only 11.1% of patients who were prescribed immunomodulators developed cholangitis over the same time period (P < 0.001).CONCLUSIONS: Our observations suggest that classes of immunosuppressive medications differentially modify the odds of acute cholangitis. Biologic therapy, ie, anti-TNF therapy, was shown to have significantly higher odds for patients developing acute cholangitis whereas immunomodulator therapy was shown to have a potential protective effect. These findings may help guide physicians in decision-making for determining appropriate immunosuppressive therapy.

  View details for DOI 10.1093/ibd/izaa317

  View details for PubMedID 33300561

• Bacterial colonization reprograms the neonatal gut metabolome NATURE MICROBIOLOGY Bittinger, K., Zhao, C., Li, Y., Ford, E., Friedman, E. S., Ni, J., Kulkarni, C. V., Cai, J., Tian, Y., Liu, Q., Patterson, A. D., Sarkar, D., Chan, S. J., Maranas, C., Saha-Shah, A., Lund, P., Garcia, B. A., Mattei, L. M., Gerber, J. S., Elovitz, M. A., Kelly, A., DeRusso, P., Kim, D., Hofstaedter, C. E., Goulian, M., Li, H., Bushman, F. D., Zemel, B. S., Wu, G. D. 2020; 5 (6): 838-+

  Abstract

  Initial microbial colonization and later succession in the gut of human infants are linked to health and disease later in life. The timing of the appearance of the first gut microbiome, and the consequences for the early life metabolome, are just starting to be defined. Here, we evaluated the gut microbiome, proteome and metabolome in 88 African-American newborns using faecal samples collected in the first few days of life. Gut bacteria became detectable using molecular methods by 16 h after birth. Detailed analysis of the three most common species, Escherichia coli, Enterococcus faecalis and Bacteroides vulgatus, did not suggest a genomic signature for neonatal gut colonization. The appearance of bacteria was associated with reduced abundance of approximately 50 human proteins, decreased levels of free amino acids and an increase in products of bacterial fermentation, including acetate and succinate. Using flux balance modelling and in vitro experiments, we provide evidence that fermentation of amino acids provides a mechanism for the initial growth of E. coli, the most common early colonizer, under anaerobic conditions. These results provide a deep characterization of the first microbes in the human gut and show how the biochemical environment is altered by their appearance.

  View details for DOI 10.1038/s41564-020-0694-0

  View details for Web of Science ID 000527689900004

  View details for PubMedID 32284564

  View details for PubMedCentralID PMC8052915

• Clinical Significance of Nonsustained Ventricular Tachycardia on Routine Monitoring of Pacemaker Patients PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY Seth, N., Kaplan, R., Bustamante, E., Kulkarni, C., Subacius, H., Rosenthal, J. E., Passman, R. 2015; 38 (8): 980-988

  Abstract

  Permanent pacemakers (PPMs) are capable of recording tachyarrhythmic events including nonsustained ventricular tachycardia (NSVT), though the clinical significance of NSVT on routine PPM evaluation is unknown. Our goals: assess the prevalence of NSVT on routine PPM follow-up and survival of PPM patients with NSVT, without NSVT, and with ventricular high rate (VHR) episodes of undefined origin.A single-center retrospective, cohort study was performed on patients implanted with PPMs capable of recording NSVT, defined as ≥5 consecutive ventricular beats at ≥170/minutes lasting <30 seconds. Patients were categorized: (1) no NSVT; (2) NSVT; or (3) VHR episodes of uncertain etiology. The primary endpoint was all-cause mortality within 6 months of last follow-up.Note that in 1,125 enrollees (51.8% male, age 74.2 ± 15.5 years, ejection fraction 57.0 ± 9.0%), 742 (66%) had no NSVT, 223 had NSVT (20%), and 160 (14%) had VHR. There were no differences in ejection fraction, diabetes, hypertension, coronary disease, prior myocardial infarction, baseline creatinine, QRS duration, prevalence of left bundle branch block, or β-blocker use among groups. "No NSVT" patients were older (P = 0.013), NSVT patients had more males (P = 0.012); atrial fibrillation and digoxin use were more prevalent in VHR patients (P < 0.01). During median follow-up of 2.8 years there were 93 deaths within 6 months of last follow-up with no differences in survival among groups (log rank P = 0.47). Age, ejection fraction at time of implant, and β-blocker use were independent predictors of survival.NSVT detected on routine PPM follow-up in this patient population with a preserved ejection fraction is not associated with long-term mortality.

  View details for DOI 10.1111/pace.12632

  View details for Web of Science ID 000358697100010

  View details for PubMedID 25790151

• Risk Prediction for Adverse Events during Initiation of Sotalol and Dofetilide for the Treatment of Atrial Fibrillation PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY Agusala, K., Oesterle, A., Kulkarni, C., Caprio, T., Subacius, H., Passman, R. 2015; 38 (4): 490-498

  Abstract

  Inpatient antiarrhythmic drug initiation for atrial fibrillation is mandated for dofetilide (DF) and is often performed for sotalol (SL), particularly if proarrhythmia risk factors are present. Whether low-risk patients can be identified to safely allow outpatient initiation is unknown.A single-center retrospective cohort study was performed on patients initiated with DF or SL. Risk factors for adverse events (AEs), defined as any arrhythmia or electrocardiogram change requiring dose reduction or cessation, were identified.Of 329 patients, 227 (69%) received SL and 102 (31%) DF. The cohort had a mean age of 63 ± 13 years; 70% of patients were male and had a baseline QTc of 440 ± 37 ms. A total of 105 AEs occurred in 92 patients: QTc prolongation or ventricular tachyarrhythmia in 70 patients (67% of AEs), bradyarrhythmias in 35 patients (33% of AEs), with some experiencing both AE types. Ventricular arrhythmias were seen in 23 patients (7%) and torsades de pointes in one (0.3%). Total AE rates were similar between drugs (P = 0.09); however, DF patients had more QTc prolongation or ventricular arrhythmias (P = 0.001). In SL patients, there were no predictors for QTc prolongation or ventricular proarrhythmia. In DF patients, higher baseline QTc interval (odds ratio = 1.64/25 ms, P = 0.01) was an independent predictor of QTc prolongation or ventricular proarrhythmias. For patients without proarrhythmia risk factors, overall AE rate was 26%.In conclusion, AEs are common during DF and SL initiation but rarely severe in hospitalized inpatients. Baseline QTc predicts AEs for DF patients only and AE are common even in "low-risk" patients. These results support in-hospital drug initiation for all DF and SL patients.

  View details for DOI 10.1111/pace.12586

  View details for Web of Science ID 000352288100012

  View details for PubMedID 25626340