Anorectal Manometry in Patients With Fecal Incontinence After Ileal Pouch-Anal Anastomosis for Ulcerative Colitis: A Cohort Study.

Background: Fecal incontinence commonly occurs in patients with ulcerative colitis and ileal pouch-anal anastomosis. There is a paucity of manometric data in pouch patients. We aimed to better define manometric parameters in pouch patients with fecal incontinence. Methods: We compared clinical and manometric variables in ulcerative colitis patients with pouch and fecal incontinence to ulcerative colitis patients with pouch without fecal incontinence and to non-ulcerative colitis patients with fecal incontinence. Manometric data for the 3 cohorts were compared to established normative data. An independent-samples t-test was performed for continuous variables, and chi-square test was used for categorical variables. Logistic regression was performed to identify predictors of incontinence in pouch patients (P < .05). Results: Among 26 pouch patients with fecal incontinence (73% female), 26 pouch patients without fecal incontinence (35% female), and 84 patients with fecal incontinence without ulcerative colitis (68% female), there were no differences in anorectal pressures between patients with fecal incontinence. Lower pressures were observed in pouch patients with fecal incontinence compared to those without fecal incontinence. Resting pressure was similar between pouch patients with fecal incontinence and healthy controls (60.9 ±â€…36.1 mmHg vs. 66.9 ±â€…3.2 mmHg, P = .40). Female sex (P = .019) and defecatory disorders (P = .033) each independently predicted fecal incontinence in pouch patients. Conclusions: Pouch patients with fecal incontinence have lower anorectal pressures compared to pouch patients without incontinence, though have similar pressures to non-ulcerative colitis patients with fecal incontinence. Pouch patients with fecal incontinence have similar resting pressures as healthy controls. Distinct manometric normative values for pouch patients are needed.

Novel autoantibody targets identified in patients with autoimmune hepatitis (AIH) by PhIP-Seq reveals pathogenic insights.

Autoimmune hepatitis (AIH) is a severe autoimmune disease, characterized by the presence of autoantibodies. However, the role of autoantibodies in the pathophysiology of AIH remains uncertain. Here, we employed Phage Immunoprecipitation-Sequencing (PhIP-Seq) to identify novel autoantibodies in AIH. Using these results, a logistic regression classifier was able to predict which patients had AIH, indicating the presence of a distinct humoral immune signature. To further investigate the autoantibodies most specific to AIH, significant peptides were identified relative to a broad array of controls (298 patients with non-alcoholic fatty liver disease (NAFLD), primary biliary cholangitis (PBC), or healthy controls). Top ranked autoreactive targets included SLA, the target of a well-recognized autoantibody in AIH, and disco interacting protein 2 homolog A (DIP2A). The autoreactive fragment of DIP2A shares a 9-amino acid stretch nearly identical to the U27 protein of HHV-6B, a virus found in the liver. In addition, antibodies against peptides derived from the leucine rich repeat N-terminal (LRRNT) domain of the relaxin family peptide receptor 1 (RXFP1) were highly enriched and specific to AIH. The enriched peptides map to a motif adjacent to the receptor binding domain, which is required for RXFP1 signaling. RXFP1 is a G protein-coupled receptor that binds relaxin-2, an anti-fibrogenic molecule shown to reduce the myofibroblastic phenotype of hepatic stellate cells. Eight of nine patients with antibodies to RXFP1 had evidence of advanced fibrosis (F3 or greater). Furthermore, serum from AIH patients positive for anti-RFXP1 antibody was able to significantly inhibit relaxin-2 signaling in the human monocytic cell line, THP1. Depletion of IgG from anti-RXFP1 positive serum abrogated this effect. These data provide supporting evidence that HHV6 plays a role in the development of AIH and point to a potential pathogenic role for anti-RXFP1 IgG in some patients. Identification of anti-RXFP1 in patient serum may enable risk stratification of AIH patients for fibrosis progression and lead to the development of novel strategies for disease intervention.

Impact of the COVID-19 pandemic on colorectal cancer screening in New York City.

BACKGROUND: The COVID-19 pandemic significantly impacted the delivery of cancer screening. The resulting decrease in outpatient visits and cancellations of non-urgent procedures have negatively affected colorectal cancer (CRC) screening. We aimed to determine the effect of the pandemic on CRC screening at a safety-net hospital and a private health system based in New York City. METHODS: We identified individuals eligible for CRC screening aged 50 to 75 years presenting for outpatient care at a safety-net public hospital and private health system in April through September of 2019 and 2020. The primary outcome was the proportion of screening-eligible patients seen in primary care who underwent CRC screening. RESULTS: The safety-net hospital had 516 (6.1% of screening-eligible individuals) and 269 (4.3%) screening tests completed in 2019 and 2020, respectively (p < 0.01). Fecal immunochemical tests (FIT) accounted for 69.6% of screening in 2019 and 88.1% in 2020. Colonoscopy accounted for 20.3% of screening in 2019 and 11.9% in 2020. The private health system had 39 (0.7%) and 21 (0.6%) screening tests completed in 2019 and 2020, respectively (p = 0.48). FIT accounted for 61.9% of screening in 2019 and 57.1% in 2020. Colonoscopy accounted for 38.1% of screening in 2019 and 42.9% in 2020. CONCLUSION: Absolute numbers of screening tests decreased for both institutions during the COVID-19 pandemic. We observed a decrease in screening uptake and increase in proportional FIT use in the safety-net hospital but no change in the private health system.

Current and Emerging Approaches to the Diagnosis and Treatment of Crohn's Disease Strictures.

The management and understanding of Crohn's disease (CD) continues to evolve quickly. Intestinal strictures were previously thought to be an inevitable result of irreversible fibrosis caused by chronic inflammation. However, increased understanding of the dynamic nature of strictures and of the pathophysiology of this condition has highlighted emerging targets for potential treatment. In the diagnosis of strictures, a distinction must be made between inflammatory and fibrotic types, as the former may respond to medical therapy. Emerging technologies, such as dual-energy computed tomography enterography and iodine density, have allowed more accurate characterization of strictures. Surgical and endoscopic treatment remains the mainstay for fibrotic strictures, but developments in systemic and intralesional biologic therapy have shown efficacy. This article reviews the pathophysiology of this debilitating complication of CD as well as current and emerging diagnostics and treatments.

Effectiveness and Harms of Colorectal Cancer Screening Strategies.

Colorectal cancer screening incorporates various testing modalities. Factors including effectiveness, harms, cost, screening interval, patient preferences, and test availability should be considered when determining which test to use. Fecal occult blood testing and endoscopic screening have the most robust evidence, while newer blood- and imaging-based techniques require further evaluation. In this review, we compare the effectiveness, harms, and costs of the various screening strategies.

Increased Colorectal Cancer Screening Sustained with Mailed Fecal Immunochemical Test Outreach.

BACKGROUND & AIMS: Reports of mailed fecal immunochemical test (FIT) outreach effectiveness over time are minimal. We aimed to better evaluate a mailed FIT program with longitudinal metrics. METHODS: A total of 10,771 patients aged 50 to 75 years not up-to-date with colorectal cancer screening were randomized to intervention or usual care. The intervention arm received an advanced notification call and informational postcard prior to a mailed FIT. Usual care was at the discretion of the primary care provider. Patients were followed for up to 2.5 years. The primary outcome was the difference in cumulative proportion of completed FIT screening between arms. Screening was further examined with the proportion of time up-to-date, consistency of adherence, and frequency of abnormal FIT. RESULTS: The cumulative proportion of FIT completion was higher in the outreach intervention (73.2% vs 55.1%; P < .001). The proportion of time covered by screening was higher in the intervention group (46.8% vs 27.3%; Δ19.6%; 95% confidence interval, 18.2%-20.9%). Patients assigned to FIT outreach were more likely to consistently complete FITs (2 completed of 2 offered) (50.1% vs 21.8%; P < .001). However, for patients who did not complete the FIT during the first cycle, only 17.1% completed a FIT during the second outreach cycle. The number and overall proportion of abnormal FIT was significantly higher in the outreach intervention (6.9% Outreach vs 4.1% Usual Care; P < .01). CONCLUSIONS: Organized mailed FIT outreach significantly increased colorectal cancer screening over multiple years in this safety-net health system. Although mailing was overall effective, the effect was modest in patients who did not complete FIT in first cycle of intervention. (ClincialTrials.gov, NCT02613260).

Selection of patients for large mailed fecal immunochemical test colorectal cancer screening outreach programs: A systematic review.

OBJECTIVE: Digital health care offers an opportunity to scale and personalize cancer screening programs, such as mailed outreach for colorectal cancer (CRC) screening. However, studies that describe the patient selection strategy and process for CRC screening are limited. Our objective was to evaluate implementation strategies for selecting patients for CRC screening programs in large health care systems. METHODS: We conducted a systematic review of 30 studies along with key informant surveys and interviews to describe programmatic implementation strategies for selecting patients for CRC screening. PubMed and Embase were searched since inception through December 2018, and hand searches were performed of the retrieved reference lists but none were incorporated (n = 0). No language exclusions were applied. RESULTS: Common criteria for outreach exclusion included: being up-to-date with routine CRC screening (n = 22), comorbidities (n = 20), and personal history (n = 22) or family history of cancer (n = 9). Key informant surveys and interviews were performed (n = 28) to understand data sources and practices for patient outreach selection, and found that 13 studies leveraged electronic medical care records, 10 studies leveraged a population registry (national, municipal, community, health), 4 studies required patient opt-in, and 1 study required primary care provider referral. Broad ranges in fecal immunochemical test completion were observed in community clinic (n = 8, 31.0-59.6%), integrated health system (n = 5, 21.2-82.7%), and national regional CRC screening programs (n = 17, 23.0-64.7%). Six studies used technical codes, and four studies required patient self-reporting from a questionnaire to participate. CONCLUSION: This systematic review provides health systems with the diverse outreach practices and technical tools to support efforts to automate patient selection for CRC screening outreach.

Texture features from computed tomography correlate with markers of severity in acute alcohol-associated hepatitis.

The aim of this study was to use texture analysis to establish quantitative CT-based imaging features to predict clinical severity in patients with acute alcohol-associated hepatitis (AAH). A secondary aim was to compare the performance of texture analysis to deep learning. In this study, mathematical texture features were extracted from CT slices of the liver for 34 patients with a diagnosis of AAH and 35 control patients. Recursive feature elimination using random forest (RFE-RF) was used to identify the best combination of features to distinguish AAH from controls. These features were subsequently used as predictors to determine associated clinical values. To compare machine learning with deep learning approaches, a 2D dense convolutional neural network (CNN) was implemented and trained for the classification task of AAH. RFE-RF identified 23 top features used to classify AAH images, and the subsequent model demonstrated an accuracy of 82.4% in the test set. The deep learning CNN demonstrated an accuracy of 70% in the test set. We show that texture features of the liver are unique in AAH and are candidate quantitative biomarkers that can be used in prospective studies to predict the severity and outcomes of patients with AAH.

Advanced Notification Calls Prior to Mailed Fecal Immunochemical Test in Previously Screened Patients: a Randomized Controlled Trial.

BACKGROUND: Phone calls as part of multimodal fecal immunochemical test (FIT) outreach are effective but resource-intensive. Previous studies of advanced notification calls before FIT mailing have not differentiated patients' prior screening status. OBJECTIVE: To determine the effectiveness of a phone call preceding mailing of a FIT kit on test completion rate for patients who have completed a prior FIT. DESIGN: Randomized controlled trial nested within a larger study. All patients were assigned to receive organized mailed FIT outreach in the larger study. PARTICIPANTS: Patients in a safety-net health setting ages 50-75 years old with a previously negative FIT. INTERVENTIONS: Patients were assigned to either receive an advanced notification phone call or no phone call preceding a mailed FIT kit. Both groups received an informational postcard prior to the mailed FIT. MAIN MEASURES: The primary outcome was FIT completion rate at 1 year. The secondary outcomes were FIT completion rates at 60, 90, and 180 days, rates stratified by demographic subgroups, and rates according to outcome of the phone call. KEY RESULTS: A total of 1645 patients were assigned to advanced notification calls and 1595 were assigned to no call preceding the FIT mailing. Although FIT completion rate was higher at day 60 (55.5% vs. 50.8%, p < 0.01), an advanced notification call did not significantly improve FIT completion at 1 year (70.9% vs. 69.9%, p = 0.52). Of the patients assigned to receive an advanced notification call, 90.5% were spoken with or left a voicemail; patients who were spoken with were more likely to complete a FIT at 1 year compared with patients who were only left a voicemail or could not be left a voicemail (79.9% vs. 69.2% vs. 49.6%, p < 0.01). CONCLUSIONS: Advanced notification phone calls prior to FIT mailing did not improve rates at 1 year for patients with a previously negative FIT.

Race/ethnicity is an independent risk factor for autoimmune hepatitis among the San Francisco underserved.

Although autoimmune hepatitis (AIH) is more common in women and affects people of all races/ethnicities, there is currently limited information regarding the relationship between race/ethnicity and AIH, especially in the context of underserved populations. We aim to evaluate the relationship between race/ethnicity and AIH and better characterize its clinical features among different racial groups. We conducted a 15-year retrospective analysis, from January 2002 to June 2017, of patients seen at Zuckerberg San Francisco General Hospital (ZSFG). Sixty-three AIH patients and 2049 non-AIH controls were eligible for the study. The main predictor of interest was race/ethnicity, and the main outcome of interest was AIH diagnosis; other secondary measures recorded include clinical features such as ALT, bilirubin, and biopsy fibrosis at presentation. In a multivariable model adjusting for age and sex, we found that black (OR 9.6, 95% CI 1.8-178), Latino (OR 25.0, 95% CI 5.3-448), and Asian/Pacific Islander (API) (OR 10.8, 95% CI 2.2-196) race/ethnicity were associated with increased odds of an AIH diagnosis compared to the white reference group. Among people of colour with AIH, there were no significant differences in baseline ALT (p = .45), total bilirubin at presentation (p = .06), fibrosis at presentation (p = .74), and hospitalization (p = .27). Race/ethnicity is an independent risk factor for AIH. The clinical features of AIH did not differ significantly among black, Latino, and API patients.