Search

Purpose Despite progress in the treatment of coronavirus disease 2019 (COVID-19), including the development of monoclonal antibodies (mAbs), more clinical data to support the use of mAbs in outpatients with COVID-19 is needed. This study is designed to determine the impact of bamlanivimab, bamlanivimab/etesevimab, or casirivimab/imdevimab on clinical outcomes within 30 days of COVID-19 diagnosis. Methods A retrospective cohort study was conducted at a single academic medical center with 3 campuses in Manhattan, Brooklyn, and Long Island, NY. Patients 12 years of age or older who tested positive for COVID-19 or were treated with a COVID-19–specific therapy, including COVID-19 mAb therapies, at the study site between November 24, 2020, and May 15, 2021, were included. The primary outcomes included rates of emergency department (ED) visit, inpatient admission, intensive care unit (ICU) admission, or death within 30 days from the date of COVID-19 diagnosis. Results A total of 1,344 mAb-treated patients were propensity matched to 1,344 patients with COVID-19 patients who were not treated with mAb therapy. Within 30 days of diagnosis, among the patients who received mAb therapy, 101 (7.5%) presented to the ED and 79 (5.9%) were admitted. Among the patients who did not receive mAb therapy, 165 (12.3%) presented to the ED and 156 (11.6%) were admitted (relative risk [RR], 0.61 [95% CI, 0.50-0.75] and 0.51 [95% CI, 0.40-0.64], respectively). Four mAb patients (0.3%) and 2.64 control patients (0.2%) were admitted to the ICU (RR, 01.51; 95% CI, 0.45-5.09). Six mAb-treated patients (0.4%) and 3.37 controls (0.3%) died and/or were admitted to hospice (RR, 1.61; 95% CI, 0.54-4.83). mAb therapy in ambulatory patients with COVID-19 decreases the risk of ED presentation and hospital admission within 30 days of diagnosis.

PDF file - 33K

MOV file - 14MB, Supplementary video SV1 highlights the 3-dimensional imaging capability of MPM

Endoscopy is widely used to detect and remove premalignant lesions with the goal of preventing gastrointestinal (GI) cancers. Because current endoscopes do not provide cellular resolution, all suspicious lesions are biopsied and subjected to histologic evaluation. Technologies that facilitate directed biopsies should decrease both procedure-related morbidity and cost. Here we explore the use of multiphoton microscopy (MPM), an optical biopsy tool that relies on intrinsic tissue emissions, to evaluate pathology in both experimental and human GI specimens, using hematoxylin and eosin (H&E)-stained sections from these tissues for comparison. After evaluating the entire normal mouse GI tract, MPM was used to investigate disease progression in mouse models of colitis and colorectal carcinogenesis. MPM provided sufficient histologic detail to identify all relevant substructures in ex vivo normal GI tissue, visualize both acute and resolving stages of colitis, and show the progression of colorectal carcinogenesis. Next, ex vivo specimens from human subjects with celiac sprue, inflammatory bowel disease, and colorectal neoplasia were imaged by MPM. Finally, colonic mucosa in live anesthetized rats was imaged in vivo using a flexible endoscope prototype. In both animal models and human specimens, MPM images showed a striking similarity to the results of H&E staining, as shown by the 100% concordance achieved by the study pathologists' diagnoses. In summary, MPM is a promising technique that accurately visualizes histology in fresh, unstained tissues. Our findings support the continued development of MPM as a technology to enhance the early detection of GI pathologies including premalignant lesions. Cancer Prev Res; 5(11); 1280–90. ©2012 AACR.

PDF file - 522K, Experimental designs for DSS and AOM models

Objective:New York City was the epicenter of the outbreak of the 2019 coronavirus disease (COVID-19) pandemic in the United States. As a large, quaternary care medical center, NYU Langone Medical Center was one of many New York medical centers that experienced an unprecedented influx of patients during this time. Clinical leadership effectively identified, oriented, and rapidly deployed a “COVID Army,” consisting of non-hospitalist physicians, to meet the needs of the patient influx. We share feedback from our providers on our processes and offer specific recommendations for systems experiencing a similar influx in the current and future pandemics.Methods:To assess the experiences and perceived readiness of these physicians (n = 183), we distributed a 32-item survey between March and June of 2020. Thematic analyses and response rates were examined to develop results.Results:Responses highlighted varying experiences and attitudes of our frontline physicians during an emerging pandemic. Thematic analyses revealed a series of lessons learned, including the need to (1) provide orientations, (2) clarify roles/workflow, (3) balance team workload, (4) keep teams updated on evolving policies, (5) make team members feel valued, and (6) ensure they have necessary tools available.Conclusions:Lessons from our deployment and assessment are scalable at other institutions.

Primary care physicians frequently evaluate patients with constipation. The history is crucial in uncovering warning symptoms and signs that warrant colonoscopy. Particular elements in the history and rectal examination also can provide clues regarding the underlying etiology. Regardless of etiology, lifestyle modifications, fiber, and laxatives are first-line therapies. Patients who fail first-line therapies can be offered second-line treatments and/or referred for testing of defecatory function. In those with severely refractory symptoms, referrals to a gastroenterologist and a surgeon should be considered.

The COVID-19 pandemic has challenged front-line clinical decision-making, leading to numerous published prognostic tools. However, few models have been prospectively validated and none report implementation in practice. Here, we use 3345 retrospective and 474 prospective hospitalizations to develop and validate a parsimonious model to identify patients with favorable outcomes within 96 h of a prediction, based on real-time lab values, vital signs, and oxygen support variables. In retrospective and prospective validation, the model achieves high average precision (88.6% 95% CI: [88.4–88.7] and 90.8% [90.8–90.8]) and discrimination (95.1% [95.1–95.2] and 86.8% [86.8–86.9]) respectively. We implemented and integrated the model into the EHR, achieving a positive predictive value of 93.3% with 41% sensitivity. Preliminary results suggest clinicians are adopting these scores into their clinical workflows.

For more than half of Crohn’s disease patients, strictures will cause bowel obstructions that require surgery within 10 years of their initial diagnosis. This study utilizes computed tomography imaging and clinical data obtained at the initial emergency room visit to create a prediction model for progression to surgery in Crohn’s disease patients with acute small bowel obstructions. A retrospective chart review was performed for patients who presented to the emergency room with an ICD-10 diagnosis for Crohn’s disease and visit diagnosis of small bowel obstruction. Two expert abdominal radiologists evaluated the CT scans for bowel wall thickness, maximal and minimal luminal diameters, length of diseased segment, passage of oral contrast, evidence of penetrating disease, bowel wall hyperenhancement or stratification, presence of a comb sign, fat hypertrophy, and small bowel feces sign. The primary outcome was progression to surgery within 6 months of presentation. The secondary outcome was time to readmission. Forty patients met the inclusion criteria, with 78% receiving medical treatment alone and 22% undergoing surgery within 6 months of presentation to the emergency room. Multivariable analysis produced a model with an AUC of 92% (95% CI 0.82–1.00), 78% sensitivity, and 97% specificity, using gender, body mass index, and the radiographic features of segment length, penetrating disease, and bowel wall hyperenhancement. The model demonstrates that routine clinical and radiographic data from an emergency room visit can predict progression to surgery, and has the potential to risk stratify patients, guide management in the acute setting, and predict readmission.

Background We aimed to characterize patients with inflammatory bowel disease (IBD) and novel coronavirus disease 2019 (COVID-19). Methods We performed a case series of patients with IBD and confirmed or highly suspected COVID-19 to assess rates of severe outcomes. Results We identified 83 patients with IBD with confirmed (54%) or highly suspected (46%) COVID-19. The overall hospitalization rate was 6%, generally comprising patients with active Crohn’s disease or older men with comorbidities, and 1 patient expired. Discussion In this series of patients with IBD, severe outcomes of COVID-19 were rare and comparable to similarly aged individuals in the general population.

Common mechanisms against small intestinal bacterial overgrowth (SIBO), including an intact ileocecal valve, gastric acid secretion, intestinal motility, and an intact immune system, are compromised in inflammatory bowel disease (IBD), and therefore, a relatively high incidence of SIBO has been reported in this population. We aimed to determine whether an improvement in IBD clinical activity scores is seen after testing and treating SIBO. A retrospective cohort study of 147 patients with inflammatory bowel disease who were referred for SIBO breath testing from 1/2012 to 5/2016 was performed. Characteristics of SIBO positive and treated patients were compared to SIBO negative patients, including the changes in Partial Mayo Score or Harvey Bradshaw Index (HBI), using Student’s t test for continuous variables and Chi-squared or Fisher’s exact test for categorical variables. 61.9% were SIBO positive and treated, and 38.1% were SIBO negative. In Crohn’s disease, the median HBI decreased from 5 to 3 and 5 to 4, in the SIBO positive and negative groups, respectively (p = 0.005). In ulcerative colitis, the Partial Mayo Score decreased from 2 to 1.5 and 2 to 1, respectively (p = 0.607). This study examines the clinical effect of testing and treating for SIBO in an IBD population. We see a significant reduction in HBI after testing for and treating SIBO. Future prospective studies are necessary to further investigate the role of SIBO in the evaluation and management of IBD.

Background To create meaningful quality improvement (QI) curricula for graduate medical education (GME) trainees, institutions strive to improve coordination of QI curricula with hospital improvement infrastructure. Objective We created a curriculum to teach residents about QI and value-based medicine (VBM) and assessed curricular effectiveness. Methods We designed a 2-week required curriculum for internal medicine residents at a large academic program. After participating in basic skills workshops, trainees developed QI/VBM project ideas with faculty and nonclinical support and pitched them to hospital leaders at the end of the rotation. Pre-post and 1-year follow-up surveys were conducted for residents to self-assess knowledge, attitudes, and skills, participation in QI/VBM projects, and career intentions. We tracked QI/VBM project implementation. Results In the first 2 years (2017–2018), 92 trainees participated, and 71 of 76 (93%) recommended the curriculum. Surveys (76 of 92, 83%) show improvement in our learning objectives (12%–60% pre to 62%–97% post; P Conclusions Our project-based curriculum culminating in a project pitch to hospital leadership was acceptable to GME trainees, improved self-assessed skills sustained at 1 year, and resulted in successfully implemented QI/VBM projects.

Ustekinumab (UST) is a monoclonal antibody inhibitor of IL-12/IL-23 approved for the treatment of Crohn’s disease (CD) and ulcerative colitis (UC). We conducted a meta-analysis to compare rates of adverse events (AEs) in randomized controlled trials (RCTs) of UST for all indications. A systematic search was performed of MEDLINE, Embase, and PubMed databases through November 2019. Study inclusion included RCTs comparing UST to placebo or other biologics in patients aged 18 years or older with a diagnosis of an autoimmune condition. Thirty RCTs with 16,068 patients were included in our analysis. Nine thousand six hundred and twenty-six subjects were included in the UST vs placebo analysis. There was no significant difference in serious or mild/moderate AEs between UST and placebo with an OR of 0.83 (95% CI 0.66, 1.05) and 1.08 (95% CI 0.99, 1.18), respectively, over a median follow-up time of 16 weeks. In a sub-analysis of CD and UC trials, no difference in serious or mild/moderate AEs in UST versus placebo was seen. UST was not associated with an increase in short-term risk of AEs.

Background Cirrhosis has been shown in small studies to be a predictor of suboptimal bowel preparation at screening colonoscopy. It has yet to be established whether patients with chronic liver disease in the absence of cirrhosis experience equally poor colon cleansing. Intestinal dysmotility related to cirrhosis might impair bowel preparation in this population more than those with chronic liver disease without cirrhosis. Objective This study compared the quality of bowel preparation in cirrhotic and non-cirrhotic patients with chronic liver disease and determined whether this influenced polyp detection rate. Methods A retrospective study of patients with chronic liver disease, both cirrhotic and non-cirrhotic, who underwent screening colonoscopy was performed. Patient characteristics, concomitant medication use, adequacy of bowel preparation, and the total number and types of polyps found were compared between cirrhotic and non-cirrhotic groups. Results 330 patients fulfilled inclusion criteria; 36% (n = 120) were cirrhotic. Cirrhotic patients had significantly worse bowel preparation scores compared with non-cirrhotics (mean 3.4 ± 1.1 vs. 3.7 ± 0.9, P = 0.003). Worse bowel preparation scores in cirrhotics vs. non-cirrhotics persisted despite controlling for age, sex, and concomitant diabetes mellitus (DM) (P = 0.0027). Among the cirrhotics, 48% had the lowest preparation scores compared with 30% of non-cirrhotics. No difference in polyp detection rate was found between cirrhotics and non-cirrhotics. Severity of cirrhosis as assessed by the MELD score did not predict worse bowel preparation. Conclusions Cirrhotics have significantly worse bowel preparation scores compared to non-cirrhotics with chronic liver disease. No correlation between MELD score and bowel preparation score was observed in the cirrhotic cohort.

Ulcerative colitis (UC), a chronic inflammatory bowel disease, extends proximally from the rectum through the length of the colon.1 Ulcerative proctitis (UP) involves inflammation limited to the rectum distal to the rectosigmoid junction, whereas ulcerative proctosigmoiditis (UPS) involves rectal and sigmoid inflammation without involvement of the descending colon. UC has been estimated to affect approximately 0.3% of the US population, or 960,000 patients; 46% of patients have UP or UPS.2,3 Current guidelines recommend rectal corticosteroids as second-line therapy for the induction of remission of patients with UP or UPS.4–6 Rectal therapies have a limited proximal distribution, with suppositories localized to the rectum, and foams and enemas capable of spreading to the sigmoid colon and splenic flexure, respectively.7–11 A combination of rectal and oral therapy is generally more efficacious than either alone for the induction of remission of UC, even in patients with extensive UC.4,5 This may be related to uniform drug distribution across affected segments in the colon.12 Rectal budesonide foam is a second-generation corticosteroid that provides uniform delivery of budesonide to the distal colon for the treatment of UP and UPS.13 Budesonide foam has been shown to be safe and efficacious for the treatment of patients with active UP or UPS in 2 identically designed, randomized, double-blind, placebo-controlled studies.14 More than half of patients in each of these studies used 5-aminosalicylic acids (5-ASAs) concomitantly with budesonide foam. In this study, the impact of baseline use of oral 5-ASA on the efficacy and safety of budesonide foam for the induction of remission of UP and UPS was examined in patients with mild to moderate disease.

INTRODUCTION: The outbreak of novel severe acute respiratory virus syndrome coronavirus 2 (SARS-CoV 2), the causative virus of coronavirus disease 2019 (COVID-19), has become a global pandemic In the United States, cases exceed 2 million, with the New York City (NYC) metropolitan area at the epicenter Patients with inflammatory bowel disease (IBD) are generally considered higher risk of infection due to immunosuppressive therapies, however, data are lacking regarding outcomes of COVID-19 in patients with IBD compared to the general population We aim to investigate the impact of IBD on COVID-19 outcomes METHODS: We prospectively collected data on all patients with IBD [Crohn's disease (CD), ulcerative colitis (UC)] with confirmed or highly suspected COVID-19 (fever and/or close contact plus respiratory symptoms) and all non-IBD patients with confirmed COVID-19 from March 3 to May 10, 2020 at an academic medical center in NYC Patient demographics, co-morbidities, and medication history were recorded The endpoints were severe outcomes of COVID-19, including hospitalization, ventilator requirement, ICU admission and death Adjusted analyses were performed for predictors of a composite endpoint of ventilator, ICU and death RESULTS: We identified 83 patients with IBD [CD (n = 56, 67%) or UC (n = 27, 33%)] with confirmed or suspected COVID-19 and 8277 non-IBD patients with confirmed COVID-19 (Table 1) IBD patients had a lower median age (34 vs 53 years;P < 0 001) and a higher proportion of Caucasians (69% vs 41%;P < 0 001) IBD patients were less likely to have any co-morbidity (29% vs 52%;P < 0 001), and had higher rates of immunomodulator (IMM) or biologic use IBD patients with confirmed COVID-19 had lower rates of hospitalizations (14% vs 51%;P < 0 001) and ICU admissions (2% vs 13%;P = 0 04;Table 2) On multivariable analysis restricted to confirmed COVID-19, the presence of IBD was not associated with severe outcomes (OR 0 55, 95% CI 0 12-2 44, P = 0 43) Age, male gender, number of comorbidities, thiopurine and steroid use were significant predictors of severe COVID-19 outcomes, while TNF-antagonists had a protective effect (Table 3) CONCLUSION: In this large cohort study, IBD was not a risk factor for severe outcomes of COVID-19 Age, co-morbidities, and exposure to thiopurines and steroids were associated with severe outcomes of COVID-19 TNF-antagonists may be protective from severe outcomes of COVID-19, but this requires further study

Limited evidence suggests that exercise may have beneficial, anti-inflammatory effects in patients with inflammatory bowel disease (IBD). The purpose of this study was to evaluate the prevalence of exercise in patients with IBD and the limitations they experience secondary to their disease. Two hundred and fifty IBD patients were prospectively enrolled in this study at an academic medical center at the time of their outpatient visits between March and October 2013. Subjects were asked to complete a one-time survey that asks questions about medical and surgical history, exercise frequency and intensity, and the limitations and barriers they experience. Two hundred and twenty-seven patients (148 female patients) completed the survey. Crohn’s disease was present in 140 patients (61.5 %), while 87 had ulcerative colitis. Forty-one patients (16.4 %) never exercised, 82 patients (32.8 %) exercised 1–2 times per week, 59 (23.6 %) exercised 3–4 times per week, and 45 (18.0 %) exercised more than four times per week. Of the 186 who regularly exercise, 95 (51 %) reported moderate exercise intensity, 61 (33 %) reported light intensity, and 30 (16 %) reported vigorous intensity. Ninety-nine patients (44 %) reported that their IBD limited their exercise for reasons including fatigue (n = 81), joint pain (n = 37), embarrassment (n = 23), weakness (n = 21), and others. Although they may benefit from exercise, IBD patients experience considerable barriers to regular exercise secondary to the relapsing and remitting nature of IBD. Larger studies are needed to determine the effects of exercise on disease symptomatology and activity.

Cerebral venous thrombosis (CVT) is a rare but devastating complication of inflammatory bowel disease (IBD). Here we describe six IBD patients with cerebral venous thrombosis. The patients presented with hours to days of headache and were found to have venous thrombosis on imaging. Four of the six patients had ulcerative colitis and two had Crohn's disease. All six patients were treated with therapeutic anticoagulation. There were two deaths; one patient became comatose and died despite anticoagulation while the other recovered well from the sinus thrombosis but died after a bowel perforation 3 weeks later. This case series demonstrates the critical need for early recognition of neurological symptoms in patients with IBD during disease flares. It is important to recognize the clinical signs in order to start anticoagulation expeditiously and improve neurological outcomes.

Background Infliximab (IFX) is commonly used in patients with inflammatory bowel disease. One common side effect of IFX is an acute infusion reaction. Despite the lack of evidence supporting their use, clinicians use various premedications to prevent acute reactions. We evaluated the effectiveness of premedications in the prevention of acute IFX infusion reactions. Methods A retrospective cohort study was performed identifying patients with a diagnosis of inflammatory bowel disease who received IFX at our institution. Information about each IFX infusion was recorded, including the dose, infusion rate, use of premedications, and any reactions. Infusions were stratified into low and high risk. In the high- and low-risk groups, the relative risk was calculated for each premedication combination used in our institution. Results Seven hundred seventy-three patients were identified; 578 patients (7090 infusions) met inclusion criteria and were included for analysis. Nine hundred eighty-six high-risk infusions were isolated; 620 (62.8%) of these infusions were administered with premedications (diphenhydramine and/or hydrocortisone) and 53 (5.4%) reactions occurred. Six thousand one hundred four low-risk infusions were identified; 2253 (36.9%) of these infusions had premedications and 61 (1.0%) reactions occurred. In both groups, none of the premedications used resulted in a significantly lower reaction rate compared with no premedication use. Conclusions In both the high- and low-risk cohorts in this study, premedication use was not effective in reducing the rate of acute IFX reactions. Given this, routine premedication use is not recommended without future randomized control trials to demonstrate efficacy.

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.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.Of the 20 patients enrolled in this study, 7 patients (35%) achieved a clinical response by week 4. Three patients (15%) 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.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.

Digestive diseases may have protean neurological manifestations, and should be considered during neurological evaluation of patients. Neurological manifestations of celiac disease (CD) may involve both central and peripheral nervous system, including syndromes of cerebellar and myoclonic ataxia, encephalopathy and dementia, seizures, CNS vasculitis and progressive multifocal leukoencephalopathy, peripheral neuropathy, and myopathy. Gluten sensitivity has been frequently implicated as a cause of neuropathy, with up to 49% of celiac disease patients experiencing some form of neuropathy and almost 40% meeting the criteria for peripheral neuropathy. Gluten ataxia is one of the most common neurological manifestations of celiac disease. Neurologic manifestations of inflammatory bowel disease (IBD) have long been recognized, with an incidence ranging from less than 1% to 35%. These manifestations may precede or, more commonly, follow a diagnosis of IBD. Hepatic encephalopathy, Wilson’s disease, and acute intermittent porphyria are examples of liver diseases associated with hepatic disorders.

Summary LGR5 and BMI1 mark intestinal stem cells in crypt base columnar cells and +4 position cells, respectively, but characterization of functional markers in these cell populations is limited. ID1 maintains the stem cell potential of embryonic, neural, and long-term repopulating hematopoietic stem cells. Here, we show in both human and mouse intestine that ID1 is expressed in cycling columnar cells, +4 position cells, and transit-amplifying cells in the crypt. Lineage tracing revealed ID1+ cells to be self-renewing, multipotent stem/progenitor cells that are responsible for the long-term renewal of the intestinal epithelium. Single ID1+ cells can generate long-lived organoids resembling mature intestinal epithelium. Complete knockout of Id1 or selective deletion of Id1 in intestinal epithelium or in LGR5+ stem cells sensitizes mice to chemical-induced colon injury. These experiments identify ID1 as a marker for intestinal stem/progenitor cells and demonstrate a role for ID1 in maintaining the potential for repair in response to colonic injury., Highlights • ID1 is expressed in mouse and human intestinal and colonic stem and progenitor cells • ID1+ cells are long-lived and multipotent • Deletion of Id1 in stem and progenitor cells sensitizes mice to colon injury, In this article, Benezra, Dannenberg, and colleagues show that the dominant-negative transcription factor ID1 marks the stem and progenitor cells of the gut and is required in the colon for an optimal response to injury in a mouse model of colitis.

International audience; INTRODUCTION:The most cost-effective diagnostic algorithm for gastroesophageal reflux disease (GERD) remains controversial. We hypothesized that prompt referral for esophageal pH monitoring is more cost-effective than prolonged empiric courses of proton-pump inhibitors (PPIs).DISCUSSION:A cost model was created based on a cohort of 100 patients with possible GERD who underwent pH monitoring. The additional costs incurred from pH monitoring were compared to the potential savings from avoiding unnecessary PPI usage in patients with a negative pH study. The costs of PPI therapy reach equivalence with pH monitoring after 6.4 to 23.7 weeks, depending on the PPI regimen. A total of 21,411 weeks of PPIs were prescribed beyond the recommended 8-week trial, of which 32 % were for patients who had a negative 24-h pH monitoring study. If the sensitivity of pH monitoring was 96 %, early referral for pH monitoring would have saved between $1,197 and $6,303 per patient over 10 years. This strategy remains cost-effective as long as the sensitivity of pH monitoring is above 35 %. Prompt referral for pH monitoring after a brief empiric PPI trial is a more cost-effective strategy than prolonged empiric PPI trials for patients with both esophageal and extraesophageal GERD symptoms.

Signaling through sphingosine-1-phosphate receptor₁ (S1P₁) promotes blood vessel barrier function. Degradation of S1P₁ results in increased vascular permeability in the lung and may explain side effects associated with administration of FTY720, a functional antagonist of the S1P₁ receptor that is currently used to treat multiple sclerosis. Ulcerative colitis (UC) is characterized by an increased density of abnormal vessels. The expression or role of S1P₁ in blood vessels in the colon has not been investigated. In the present study, we show that S1P₁ is overexpressed in the colonic mucosa of UC patients. This increase in S1P₁ levels reflects increased vascular density in the inflamed mucosa. Genetic deletion of S1pr1 in mice increases colonic vascular permeability under basal conditions and increases bleeding in experimental colitis. In contrast, neither FTY720 nor AUY954, two S1P receptor-targeting agents, increases bleeding in experimental colitis. Taken together, our findings demonstrate that S1P₁ is critical to maintaining colonic vascular integrity and may play a role in UC pathogenesis.

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 Systematic reviews with meta-analyses and meta-regression suggest that timely probiotic use can prevent Clostridium difficile infection (CDI) in hospitalized adults receiving antibiotics, but the cost effectiveness is unknown. We sought to evaluate the cost effectiveness of probiotic use for prevention of CDI versus no probiotic use in the United States. Methods We programmed a decision analytic model using published literature and national databases with a 1-year time horizon. The base case was modeled as a hypothetical cohort of hospitalized adults (mean age 68) receiving antibiotics with and without concurrent probiotic administration. Projected outcomes included quality-adjusted life-years (QALYs), costs (2013 US dollars), incremental cost-effectiveness ratios (ICERs; $/QALY), and cost per infection avoided. One-way, two-way, and probabilistic sensitivity analyses were conducted, and scenarios of different age cohorts were considered. The ICERs less than $100000 per QALY were considered cost effective. Results Probiotic use dominated (more effective and less costly) no probiotic use. Results were sensitive to probiotic efficacy (relative risk 1.6%), the risk of probiotic-associated bactermia/fungemia (65). In probabilistic sensitivity analysis, at a willingness-to-pay threshold of $100000/QALY, probiotics were the optimal strategy in 69.4% of simulations. Conclusions Our findings suggest that probiotic use may be a cost-effective strategy to prevent CDI in hospitalized adults receiving antibiotics age 65 or older or when the baseline risk of CDI exceeds 1.6%.

Background: Escherichia coli is increasingly implicated in the pathogenesis of ileal Crohn's disease (ICD), offering a potential therapeutic target for disease management. Empirical antimicrobial targeting of ileal E. coli has advantages of economy and speed of implementation, but relies on uniform susceptibility of E. coli to routinely selected antimicrobials to avoid apparent treatment failure. Therefore, we examined the susceptibility of ileal E. coli to such antimicrobials. Methods: E. coli from 32 patients with ICD and 28 with normal ileum (NI) were characterized by phylogroup, pathotype, antimicrobial susceptibility, and presence of antimicrobial resistance genes. Results: In all, 17/32 ICD and 12/28 NI patients harbored ≥1 E. coli strain; 10/24 E. coli strains from ICD and 2/14 from NI were nonsusceptible to ≥1 antimicrobial in ≥3 categories (multidrug-resistant). Resistance to amoxicillin/clavulanic-acid, cefoxitin, chloramphenicol, ciprofloxacin, gentamicin, and rifaximin was restricted to ICD, with 10/24 strains from 8/17 patients resistant to ciprofloxacin or rifaximin (P < 0.01). Adherent-invasive E. coli (AIEC) were isolated from 8/32 ICD and 5/28 NI, and accounted for 54% and 43% of E. coli strains in these groups. In all, 8/13 AIEC strains from ICD (6/8 patients) versus 2/6 NI (2/5 patients) showed resistance to the macrophage-penetrating antimicrobials ciprofloxacin, clarithromycin, rifampicin, tetracycline, and trimethoprim/sulfamethoxazole. Resistance was associated with tetA, tetB, tetC, blaTEM, blaoxa-1, sulI, sulII, dhfrI, dhfrVII, ant(3″)-Ia, and catI genes and prior use of rifaximin (P < 0.01). Conclusions: ICD-associated E. coli frequently manifest resistance to commonly used antimicrobials. Clinical trials of antimicrobials against E. coli in ICD that are informed by susceptibility testing, rather than empirical selection, are more likely to demonstrate valid outcomes of such therapy. (Inflamm Bowel Dis 2012;)

OBJECTIVE: Tumor necrosis factor (TNF) inhibitors can be used to treat inflammatory bowel disease (IBD) but may lead to anti-nuclear antibody (ANA) positivity and lupus-like reactions. Because of its unique structure, certolizumab has lower rates of these complications. We sought to investigate whether patients who have had lupus-like reactions to infliximab or adalimumab would be able to tolerate certolizumab. METHODS: We performed a retrospective analysis on the 23 patients at the Roberts Inflammatory Bowel Disease Center who received certolizumab for the treatment of Crohn's disease from March 2008 to June 2009. We identified 6 patients who were switched to this drug because of lupus-like reactions from prior anti-TNF therapy and had documented ANA after the reaction and prior to certolizumab initiation. We then rechecked the ANA status after certolizumab initiation. RESULTS: Five out of 6 patients had a resolution of their arthralgias or lupus-like symptoms after being switched to certolizumab (P

Background Budesonide foam, a rectally administered, second-generation corticosteroid with extensive hepatic first-pass metabolism, is efficacious for the treatment of mild-to-moderate ulcerative proctitis and ulcerative proctosigmoiditis. Aim The aim of this study was to comprehensively assess the safety and pharmacokinetic profile of budesonide foam. Methods Data from five phase III studies were pooled to further evaluate safety, including an open-label study (once-daily treatment for 8 weeks), an active-comparator study (once-daily treatment for 4 weeks), and two placebo-controlled studies and an open-label extension study (twice-daily treatment for 2 weeks, then once daily for 4 weeks). Data from the placebo-controlled studies and two phase I studies (i.e., patients with mild-to-moderate ulcerative colitis and healthy volunteers) were pooled to evaluate the pharmacokinetics of budesonide foam. Results A similar percentage of patients reported adverse events in the budesonide foam and placebo groups, with the majority of adverse events being mild or moderate in intensity (93.3 vs 96.0 %, respectively). Adverse events occurred in 41.4 and 36.3 % of patients receiving budesonide foam and placebo, respectively. Mean morning cortisol concentrations remained within the normal range for up to 8 weeks of treatment; there were no clinically relevant effects of budesonide foam on the hypothalamic–pituitary–adrenal axis. Population pharmacokinetic analysis demonstrated low systemic exposure after budesonide foam administration. Conclusions This integrated analysis demonstrated that budesonide foam for the induction of remission of distal ulcerative colitis is safe overall, with no clinically relevant effects on the hypothalamic–pituitary–adrenal axis.

Background This study evaluated the effects of the Breath-Body-Mind Workshop (BBMW) (breathing, movement, and meditation) on psychological and physical symptoms and inflammatory biomarkers in inflammatory bowel disease (IBD). Methods Twenty-nine IBD patients from the Jill Roberts IBD Center were randomized to BBMW or an educational seminar. Beck Anxiety Inventory, Beck Depression Inventory, Brief Symptom Inventory 18, IBD Questionnaire, Perceived Disability Scale, Perceived Stress Questionnaire, Digestive Disease Acceptance Questionnaire, Brief Illness Perception Questionnaire, fecal calprotectin, C-reactive protein, and physiological measures were obtained at baseline and weeks 6 and 26. Results The BBMW group significantly improved between baseline and week 6 on Brief Symptom Inventory 18 (P = 0.02), Beck Anxiety Inventory (P = 0.02), and IBD Questionnaire (P = 0.01) and between baseline and week 26 on Brief Symptom Inventory 18 (P = 0.04), Beck Anxiety Inventory (P = 0.03), Beck Depression Inventory (P = 0.01), IBD Questionnaire (P = 0.01), Perceived Disability Scale (P = 0.001), and Perceived Stress Questionnaire (P = 0.01) by paired t tests. No significant changes occurred in the educational seminar group at week 6 or 26. By week 26, median C-reactive protein values decreased significantly in the BBMW group (P = 0.01 by Wilcoxon signed-rank test) versus no significant change in the educational seminar group. Conclusions In patients with IBD, participation in the BBMW was associated with significant improvements in psychological and physical symptoms, quality of life, and C-reactive protein. Mind-body interventions, such as BBMW, which emphasize Voluntarily Regulated Breathing Practices, may have significant long-lasting benefits for IBD symptoms, anxiety, depression, quality of life, and inflammation. BBMW, a promising adjunctive treatment for IBD, warrants further study.