Faculty Bibliography

BACKGROUND: Recent trials suggest fecal microbiota transplantation (FMT) with repeated enemas and high-diversity FMT donors is a promising treatment to induce remission in ulcerative colitis. METHODS: We designed a prospective, open-label pilot study to assess the safety, clinical efficacy, and microbial engraftment of single FMT delivery by colonoscopy for active ulcerative colitis using a 2-donor fecal microbiota preparation (FMP). Safety and clinical endpoints of response, remission, and mucosal healing at week 4 were assessed. Fecal DNA and rectal biopsies were used to characterize the microbiome and mucosal CD4 T cells, respectively, before and after FMT. RESULTS: Of the 20 patients enrolled in this study, 7 patients (35%) achieved a clinical response by week 4. Four patients (20%) were in remission at week 4 and 2 of these patients (10%) achieved mucosal healing. Three patients (15%) required escalation of care. No serious adverse events were observed. Microbiome analysis revealed that restricted diversity of recipients pre-FMT was significantly increased by high-diversity 2-donor FMP. The microbiome of recipients post-transplant was more similar to the donor FMP than the pretransplant recipient sample in both responders and nonresponders. Notably, donor composition correlated with clinical response. Mucosal CD4 T-cell analysis revealed a reduction in both Th1 and regulatory T-cells post-FMT. CONCLUSIONS: High-diversity, 2-donor FMP delivery by colonoscopy seems safe and effective in increasing fecal microbial diversity in patients with active ulcerative colitis. Donor composition correlated with clinical response and further characterization of immunological parameters may provide insight into factors influencing clinical outcome.

BACKGROUND: Patients admitted to the Medicine Service from the Emergency Department (ED) at times when no beds are available pose a particular challenge to workflow, staffing and patient care. Due to the expansion of our clinically integrated network and recruitment of high-volume surgical teams, the hospital daily census surged, causing an increase in the average number of patients admitted to the hospital but physically located in the ED. The Hospitalist program was charged with developing a coordinated strategy to manage these patients METHODS: In 2015, we created an ED Hospitalist Team composed of a hospitalist and a nurse practitioner to care for patients admitted to the Medicine Service but awaiting beds on the floor. We purposely created this model so that the medicine teams could focus on caring for patients on their own units and not disrupt their workflow by traveling to the ED. We created a Checklist (Figure 1) for this ED Hospitalist Team to ensure that protocols and pathways were followed, just as they would be on the medical floor. We partnered with ED leadership to identify workspace and standardize handoffs, as well as with leadership from Social Work to proactively identify complex situations starting on hospital day 0. Patients requiring ICU level care were excluded (as intensivists were involved immediately). All patients admitted to the medicine service (i.e. patients who would ultimately be cared for on the general medicine, cardiac, oncologic or hepatobiliary teams), were cared for by the ED Hospitalist team until a bed became available on the appropriate unit. RESULTS: The average number of patients admitted to the hospital, but physically located in the ED increased from 2.1/day in April 2015 to 14.5/ day in October 2016. At least 70% of these patients were admitted to the Medicine Service. Even with this increase, the observed to expected length of stay (O:E LOS) for Medicine patients remained at 0.92. The discharge before noon rate increased from 39 to 43% during this same period. CONCLUSIONS: We have demonstrated a strategic and sustainable approach for managing a growing number of patients who are admitted to the Medicine Service but physically located in the ED. By consolidating our resources in creating an ED Hospitalist team, we are able to maintain our workflow efficiencies on the floor, as demonstrated by the O:E LOS and our improved discharge before noon rate. (Figure Presented)

BACKGROUND: The CDC reports that 5% of hospitalized patients develop hospital acquired infections, which are responsible for 100,000 deaths annually. Poor hand hygiene compliance on the Medicine service placed patients at higher risk for infection and was the impetus for our Clean Hands Save Lives Initiative. METHODS: The Clean Hands Save Lives initiative was a triple-prong systems based strategy that required the leadership of the medical director and nurse manager and the engagement of the entire floor. First, unit leadership dedicated a portion of the the morning unit-based safety huddle to identify daily hand washing champions. Each day a new group of champions was identified, including 2 nurses, one one floor patient unit technician, and two physicians. Champions were responsible for reinforcing correct hand hygiene procedures in real time, promoting a culture of "if you see something, say something."Each week, 35 different health care providers were hand-hygiene champions, hardwiring best practice. Second, proper hand hygiene procedures were reinforced at the safety huddle several times a week and Purell dispensers were installed outside every patient room. Third, an email was sent to each team member regarding the hand hygiene initiative at the start of each rotation. Real time feedback on hand hygiene technique was provided by unit leadership. RESULTS: At the start of the initiative in quarter 1 of 2015, hand hygiene compliance for the 17 East Medical Unit was at 64%. By quarter 1 of 2016, hand hygiene compliance was at 93 and has remained above 90% for the past 4 quarters (Figure 1). CONCLUSIONS: Successful implementation of our Clean Hands Save Lives Initiative on a hospitalist led medicine unit was due in large part to making this a daily focus of all members of the team, leading to unit culture change. The interdisciplinary approach to the problem, daily reinforcement of the initiative, regular education of unit staff and ease of practicing proper hand hygiene all were contributing factors to its success and sustainability. The initiative is now practiced in all units on the Medicine service

BACKGROUND: Prior To March 2016 interdisciplinary rounds were held in the back of the nurses' stations on two inpatient medial units. Patients satisfaction scores around the discharge process and communication were consistently low. Medical director and nurse manager dyad leadership teams redesigned interdisciplinary rounds to improve communication between the patient and the health care team. METHODS: With the At-The-Bedside Walking Interdisciplinary Rounds initiative, every patient is visited by the entire interdisciplinary team each afternoon. The interdisciplinary team consists of the Hospitalist, the unit nurse manager, the bedside nurse, the care manager, the social worker and the medicine resident. Each visit takes 3-5 min and is led by the resident, who starts by introducing everymember of the team. Importantly, the patient is surrounded by every person on the team (a design to be literally and figuratively patient centric). Rounds are structured around four simple questions designed to effectively communicate the diagnosis, the milestones for discharge and the discharge disposition and date. Updated information is written on the patient's white board, located at the foot of the bed. Patients and caregivers have an opportunity to ask clarifying questions. Moreover, the patient can experience first-hand the collaboration that takes place amongst the team members with a streamlined and unified message. The team will use a video language access network for interpreter services for those patients who feel more comfortable speaking in their native language. For those patients who prefer not to discuss discharge planning in large groups, members of the team will return individually. RESULTS: When comparing pre (Q1CY2016, N= 81) and post (Q2CY2016, N= 80) intervention top box HCAHPS patient satisfaction scores, the results were mixed. Care transitions improved slightly from46 to 48 and communication with doctors increased from74 to 75%. Communication with nurses decreased from 78 to 75%. Discharge information, however, improved from 78 to 84%. CONCLUSIONS: While these early results are disappointing, we believe that patient centered care starts with streamlined communication at the bedside with the interdisciplinary team. We will be tweaking how to better contextualize these rounds for patients in the future

Peripheral spondyloarthritis (SpA) is a common extraintestinal manifestation in patients with active inflammatory bowel disease (IBD) characterized by inflammatory enthesitis, dactylitis, or synovitis of nonaxial joints. However, a mechanistic understanding of the link between intestinal inflammation and SpA has yet to emerge. We evaluated and functionally characterized the fecal microbiome of IBD patients with or without peripheral SpA. Coupling the sorting of immunoglobulin A (IgA)-coated microbiota with 16S ribosomal RNA-based analysis (IgA-seq) revealed a selective enrichment in IgA-coated Escherichia coli in patients with Crohn's disease-associated SpA (CD-SpA) compared to CD alone. E. coli isolates from CD-SpA-derived IgA-coated bacteria were similar in genotype and phenotype to an adherent-invasive E. coli (AIEC) pathotype. In comparison to non-AIEC E. coli, colonization of germ-free mice with CD-SpA E. coli isolates induced T helper 17 cell (TH17) mucosal immunity, which required the virulence-associated metabolic enzyme propanediol dehydratase (pduC). Modeling the increase in mucosal and systemic TH17 immunity we observed in CD-SpA patients, colonization of interleukin-10-deficient or K/BxN mice with CD-SpA-derived E. coli lead to more severe colitis or inflammatory arthritis, respectively. Collectively, these data reveal the power of IgA-seq to identify immunoreactive resident pathosymbionts that link mucosal and systemic TH17-dependent inflammation and offer microbial and immunophenotype stratification of CD-SpA that may guide medical and biologic therapy.

BACKGROUND: Rectal budesonide foam is a second-generation corticosteroid efficacious for active mild to moderate ulcerative proctitis and ulcerative proctosigmoiditis. This subgroup analysis examined the impact of baseline oral 5-aminosalicylic acid (5-ASA) on the efficacy and safety of budesonide foam in patients with mild to moderate ulcerative proctitis or ulcerative proctosigmoiditis. METHODS: Patients received budesonide foam 2 mg/25 mL twice daily for 2 weeks, then once daily for 4 weeks, or placebo, with or without continued stable dosing of baseline oral 5-ASAs, for remission induction at week 6 (primary endpoint) in 2 identically designed, randomized, double-blind, phase 3 studies. RESULTS: Of the 267 and 279 patients randomized to treatment with budesonide foam or placebo (pooled population), 55.1% and 55.2%, respectively, reported baseline 5-ASA use. A significantly greater percentage of patients achieved remission with budesonide foam versus placebo, either with (42.2% versus 31.8%, respectively; P = 0.03) or without (40.0% versus 14.4%; P < 0.0001) baseline 5-ASA use at week 6. A significantly greater percentage of patients achieved a Modified Mayo Disease Activity Index rectal bleeding subscale score of 0 at week 6, regardless of baseline 5-ASA use (5-ASA, 50.3% versus 35.7%; P = 0.003: no 5-ASA, 45.8% versus 19.2%; P < 0.0001). The frequency of adverse events was comparable between groups, regardless of baseline 5-ASA use. CONCLUSIONS: Budesonide foam was efficacious and safe for induction of remission of mild to moderate ulcerative proctitis and ulcerative proctosigmoiditis in patients receiving oral 5-ASA at baseline and those who were not (Clinicaltrials.gov: NCT01008410 and NCT01008423).This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially.

BACKGROUND AND AIMS: Our understanding of malignancy associated with immunosuppression in patients with inflammatory bowel disease (IBD) comes from studies of individuals with no history of cancer. We investigated whether patients with IBD and a history of cancer who were subsequently immunosuppressed have an increased risk of developing incident cancer. METHODS: We performed a retrospective analysis of data from 333 patients with IBD treated at 7 academic medical centers who developed cancer and subsequently received treatment with anti-tumor necrosis factor (TNF), anti-TNF with an anti-metabolite (thiopurines, methotrexate), anti-metabolites, or no subsequent exposure to immunosuppressive agents (controls). We collected data on their primary outcomes of incident cancers (new or recurrent). Hazard ratios (HRs) were calculated using Cox proportional hazards and Kaplan-Meier survival curves; study groups were compared using the Log-Rank test. RESULTS: During the follow-up period, 90 patients (27%) developed an incident cancer. Patient characteristics between groups differed, but matching was not possible due to the relatively small sample sizes. There was no difference in time to (p=0.14) or type of (p= 0.61) incident cancer among the 4 groups. After adjusting for recurrence risk for type of prior cancer, there was no difference in risk of incident cancer (HR for anti-TNF=0.32; 95% confidence interval [CI], 0.09-1.09; HR for anti-TNF with an anti-metabolite=0.64; 95% CI, 0.26-1.59; HR for an anti-metabolite=1.08; 95% CI, 0.54-2.15) or time to subsequent cancer between study arms (p=.22). CONCLUSION: Based on a retrospective study, in patients with IBD and a history of cancer, exposure to an anti-TNF agent or an anti-metabolite following cancer was not associated with an increased risk of incident cancer, compared to patients who did not receive immunosuppression. Larger, matched, prospective studies are needed to confirm these findings.