All Publications


  • Clinical use of shear-wave elastography for detecting liver fibrosis in children and adolescents with cystic fibrosis. Pediatric radiology Levitte, S. n., Lee, L. W., Isaacson, J. n., Zucker, E. J., Milla, C. n., Barth, R. A., Sellers, Z. M. 2021

    Abstract

    Complications from liver cirrhosis are a leading cause of death in children with cystic fibrosis. Identifying children at risk for developing liver cirrhosis and halting its progression are critical to reducing liver-associated mortality.Quantitative US imaging, such as shear-wave elastography (SWE), might improve the detection of liver fibrosis in children with cystic fibrosis (CF) over gray-scale US alone. We incorporated SWE in our pediatric CF liver disease screening program and evaluated its performance using magnetic resonance (MR) elastography.Ninety-four children and adolescents with CF underwent 178 SWE exams, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT) and platelet measurements. Of these, 27 children underwent 34 MR elastography exams. We evaluated SWE performance using 6-MHz and 9-MHZ point SWE, and 9-MHz two-dimensional (2-D) SWE.The 6-MHz point SWE was the only method that correlated with MR elastography (r=0.52; 95% confidence interval [CI] 0.20-0.74; P=0.003). SWE of 1.45 m/s distinguished normal from abnormal MR elastography (79% sensitivity, 100% specificity, 100% positive predictive value [PPV], 55% negative predictive value [NPV], area under the receiver operating characteristic [AUROC] curve 0.94). SWE of 1.84 m/s separated mild-moderate (3.00-4.77 kPa) from severe (>4.77 kPa) MR elastography (88% sensitivity, 86% specificity, 78% PPV, 93% NPV, AUROC 0.79). Elevations of AST, ALT, GGT and thrombocytopenia were associated with higher SWE. AST-to-platelet ratio index of 0.42, fibrosis-4 of 0.29, and GGT-to-platelet ratio of 1.43 all had >95% NPV for SWE >1.84 m/s.Given its correlation with MR elastography, SWE might be a clinically useful predictor of liver fibrosis. We identified imaging criteria delineating the use of SWE to identify increased liver stiffness in children with CF. With multicenter validation, these data might be used to improve the detection and monitoring of liver fibrosis in children with CF.

    View details for DOI 10.1007/s00247-021-05015-w

    View details for PubMedID 33759025

  • Artificial intelligence applications in inflammatory bowel disease: Emerging technologies and future directions. World journal of gastroenterology Gubatan, J. n., Levitte, S. n., Patel, A. n., Balabanis, T. n., Wei, M. T., Sinha, S. R. 2021; 27 (17): 1920-1935

    Abstract

    Inflammatory bowel disease (IBD) is a complex and multifaceted disorder of the gastrointestinal tract that is increasing in incidence worldwide and associated with significant morbidity. The rapid accumulation of large datasets from electronic health records, high-definition multi-omics (including genomics, proteomics, transcriptomics, and metagenomics), and imaging modalities (endoscopy and endomicroscopy) have provided powerful tools to unravel novel mechanistic insights and help address unmet clinical needs in IBD. Although the application of artificial intelligence (AI) methods has facilitated the analysis, integration, and interpretation of large datasets in IBD, significant heterogeneity in AI methods, datasets, and clinical outcomes and the need for unbiased prospective validations studies are current barriers to incorporation of AI into clinical practice. The purpose of this review is to summarize the most recent advances in the application of AI and machine learning technologies in the diagnosis and risk prediction, assessment of disease severity, and prediction of clinical outcomes in patients with IBD.

    View details for DOI 10.3748/wjg.v27.i17.1920

    View details for PubMedID 34007130

    View details for PubMedCentralID PMC8108036

  • Prevalence, risk factors and clinical outcomes of COVID-19 in patients with a history of pancreatitis in Northern California. Gut Gubatan, J. n., Levitte, S. n., Patel, A. n., Balabanis, T. n., Sharma, A. n., Jones, E. n., Lee, B. n., Manohar, M. n., Swaminathan, G. n., Park, W. n., Habtezion, A. n. 2020

    View details for DOI 10.1136/gutjnl-2020-321772

    View details for PubMedID 32493828

  • SARS-CoV-2 Testing, Prevalence, and Predictors of COVID-19 in Patients with Inflammatory Bowel Disease in Northern California. Gastroenterology Gubatan, J. n., Levitte, S. n., Balabanis, T. n., Patel, A. n., Sharma, A. n., Habtezion, A. n. 2020

    View details for DOI 10.1053/j.gastro.2020.05.009

    View details for PubMedID 32387541

  • Biologics During Pregnancy in Women With Inflammatory Bowel Disease and Risk of Infantile Infections: A Systematic Review and Meta-Analysis. The American journal of gastroenterology Gubatan, J. n., Nielsen, O. H., Levitte, S. n., Juhl, C. B., Maxwell, C. n., Streett, S. E., Habtezion, A. n. 2020

    Abstract

    Biologics, such as tumor necrosis factor inhibitors, anti-integrins and anticytokines, are therapies for inflammatory bowel disease (IBD) that may increase the risk of infection. Most biologics undergo placental transfer during pregnancy and persist at detectable concentrations in exposed infants. Whether this is associated with an increased risk of infantile infections is controversial. We performed a systematic review and meta-analysis evaluating the risk of infantile infections after in utero exposure to biologics used to treat IBD.We searched PubMed, Embase, Scopus, Web of Science, and CENTRAL from inception to June 2020 to evaluate the association of biologic therapy during pregnancy in women with IBD and risk of infantile infections. Odds ratios of outcomes were pooled and analyzed using a random effects model.Nine studies met the inclusion criteria comprising 8,013 women with IBD (5,212 Crohn's disease, 2,801 ulcerative colitis) who gave birth to 8,490 infants. Biologic use during pregnancy was not associated with an increased risk of all infantile infections (odds ratio [OR] 0.91, 95% confidence interval [CI] 0.73-1.14, I = 30%). In a subgroup analysis for the type of infection, biologic use was associated with increased infantile upper respiratory infections (OR 1.57, 95% CI 1.02-2.40, I = 4%). Biologic use during pregnancy was not associated with infantile antibiotic use (OR 0.91, 95% CI 0.73-1.14, I = 30%) or infection-related hospitalizations (OR 1.33, 95% CI 0.95-1.86, I = 26%).Biologics use during pregnancy in women with IBD is not associated with the overall risk of infantile infections or serious infections requiring antibiotics or hospitalizations but is associated with an increased risk of upper respiratory infections.

    View details for DOI 10.14309/ajg.0000000000000910

    View details for PubMedID 33110017

  • Lysosomal Disorders Drive Susceptibility to Tuberculosis by Compromising Macrophage Migration CELL Berg, R. D., Levitte, S., O'Sullivan, M. P., O'Leary, S. M., Cambier, C. J., Cameron, J., Takaki, K. K., Moens, C. B., Tobin, D. M., Keane, J., Ramakrishnan, L. 2016; 165 (1): 139-152

    Abstract

    A zebrafish genetic screen for determinants of susceptibility to Mycobacterium marinum identified a hypersusceptible mutant deficient in lysosomal cysteine cathepsins that manifests hallmarks of human lysosomal storage diseases. Under homeostatic conditions, mutant macrophages accumulate undigested lysosomal material, which disrupts endocytic recycling and impairs their migration to, and thus engulfment of, dying cells. This causes a buildup of unengulfed cell debris. During mycobacterial infection, macrophages with lysosomal storage cannot migrate toward infected macrophages undergoing apoptosis in the tuberculous granuloma. The unengulfed apoptotic macrophages undergo secondary necrosis, causing granuloma breakdown and increased mycobacterial growth. Macrophage lysosomal storage similarly impairs migration to newly infecting mycobacteria. This phenotype is recapitulated in human smokers, who are at increased risk for tuberculosis. A majority of their alveolar macrophages exhibit lysosomal accumulations of tobacco smoke particulates and do not migrate to Mycobacterium tuberculosis. The incapacitation of highly microbicidal first-responding macrophages may contribute to smokers' susceptibility to tuberculosis.

    View details for DOI 10.1016/j.cell.2016.02.034

    View details for Web of Science ID 000372785600016

    View details for PubMedCentralID PMC4819607