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Ulcerative colitis (UC) is an inflammatory intestinal disorder driven by mucosal immune and stromal subsets, culminating in epithelial injury. Vedolizumab (VDZ) is an anti-integrin monoclonal antibody that is effective for treating UC. VDZ is thought to primarily inhibit lymphocyte trafficking to the intestine, but its effect on other cell subsets is less well characterized. To identify the inflammatory cells that contribute to colitis and respond to VDZ, we performed a single-cell transcriptomic and proteomic analysis of peripheral blood and colonic biopsies in healthy controls (HC) and patients with UC on either aminosalicylates or VDZ. We identified mononuclear phagocytes (MNPs) as a primary target of VDZ, with comparatively modest effects on lymphocytes. Spatial proteomics and transcriptomics demonstrated increased density and proximity of MNP and fibroblast subsets in UC biopsies when compared to HC, with inhibition by VDZ. VDZ non-responders were enriched for activated fibroblast and MNP signatures in a validation cohort.

BackgroundTo reduce unnecessary ambulatory gastroenterology (GI) visits and increase access to GI care, San Francisco Health Network gastroenterologists and primary care providers implemented guidelines in 2013 that discharged certain patients back to primary care after endoscopy with formal written recommendations. This study assesses the longer-term impact of this policy on GI clinic access, workflow, and provider satisfaction.MethodsAn email-based survey assessed gastroenterologist and primary care provider (PCP) opinions about the discharge process. Administrative data and chart review were used to assess clinic access, intervention fidelity, and re-referral rates.Results102/299 (34%) of PCPs and 5/7 (71%) of gastroenterologists responded to the survey. 74% of PCPs and 100% of gastroenterologists were satisfied or very satisfied with the discharge process. 80% of gastroenterologists believed the discharge process decreased their workload, while 53.5% of primary care providers believed it increased their workload. 6.7% of patients discharged to primary care in 2013 had re-referrals to GI. Wait time for the third-next-available new outpatient GI clinic appointment had previously decreased from 158 days (2012, pre-intervention) to 74 days (2013, post-intervention). In 2015, wait time was 19 days (p < 0.001 for 2012 vs. 2015).ConclusionsPrimary care providers and gastroenterologists are satisfied with an intervention to discharge patients from gastroenterology to primary care after certain endoscopic procedures, although this conclusion is limited by a relatively low PCP survey response rate. Discharging appropriate patients using consensus criteria from the gastroenterology clinic was instrumental in sustainably reducing clinic wait times with low re-referral rates.Electronic supplementary materialThe online version of this article (10.1186/s12913-017-2819-6) contains supplementary material, which is available to authorized users.

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