The Relationship Between the Endoscopic Healing Index, Fecal Calprotectin, and Magnetic Resonance Enterography in Crohn's Disease.

INTRODUCTION: The serum-based endoscopic healing index (EHI) test identifies endoscopic Crohn's disease (CD) activity. Data are lacking on the relationship between EHI with other endpoints. We assessed the relationship between EHI and the simplified Magnetic Resonance Index of Activity. MATERIALS AND METHODS: Data were prospectively collected on patients with CD with either an EHI or fecal calprotectin (FCAL) within 90 days of magnetic resonance enterography (MRE). Diagnostic accuracy was assessed using area under the receiver operator characteristics. Proportions with any, severe, and terminal ileum MR inflammation were compared above/below identified thresholds for both EHI and FCAL. RESULTS: A total of 241 MREs paired to either EHI or FCAL from 155 patients were included. Both EHI and FCAL had similar accuracy to diagnose inflammation (area under the receiver operator characteristics: EHI: 0.635 to 0.651, FCAL: 0.680 to 0.708). Optimal EHI values were 42 and 26 for inflammation on MRE and endoscopy, respectively. Patients with EHI ≥42 (100% vs. 63%, P=0.002), FCAL >50 µg/g (87% vs. 64%, P<0.001) and FCAL >250 µg/g (90% vs. 75%, P=0.02) had higher rates of simplified Magnetic Resonance Index of Activity ≥1 compared with lower values. EHI differentiated ileitis numerically more than FCAL (delta: 24% to 25% vs. 11% to 21%). Patients with FCAL ≥50 µg/g had higher rates of severe inflammation compared with FCAL <50 µg/g (75% vs. 47%, P<0.001), whereas smaller differentiation existed for EHI threshold of 42 (63% vs. 49%, P=0.35). CONCLUSION: Both EHI and FCAL were specific in their confirmation of inflammation and disease activity on MRE in patients with CD. However, MRE-detected inflammation was frequently present in the presence of low EHI and FCAL in similar proportions.

A Quality Improvement Initiative Is Associated With Reduced Time to Administer Biologics and Small Molecules and Emergency Room Visits in Inflammatory Bowel Disease.

BACKGROUND: Delays in biologic or small molecule medication administration are associated with increased adverse events, hospitalization, and surgery in inflammatory bowel disease (IBD). We evaluated the impact of a quality improvement (QI) intervention on the time to administration of biologics or small molecules (TABS) in IBD. METHODS: Data were retrospectively extracted for IBD patients prescribed biologics or small molecules from a convenience sample of providers participating in an accredited QI educational intervention (baseline cohort). Subsequent to the intervention, data were prospectively collected from patients prescribed these medications (postintervention cohort). Dates related to steps between a treatment decision to medication administration were collected. The primary outcome compared TABS in baseline and postintervention cohorts. RESULTS: Eighteen physicians provided survey and patient data for 200 patients in each cohort (n=400). The median time to medication administration (TABS) decreased from baseline to postintervention cohorts (30 vs. 26 d, P=0.04). Emergency room visits before medication administration also decreased (25.5% vs. 12.5%, P=0.001). Similar numerical TABS reductions were observed in subgroups limited to physicians providing patients to both cohorts and for individual medications prescribed. Primary contributors to delays included filling prescriptions subsequent to insurance approval and dispensation subsequent to this. CONCLUSIONS: A QI intervention successfully reduced medication administration times (TABS) by accelerating provider-dependent steps. This intervention was associated with reduced emergency room visits. We propose TABS as a quality metric to assess the effective delivery of therapies in IBD. Further evaluation of QI interventions, patient education on prescription drug insurance, and quality metrics are warranted.

Inflammatory bowel disease readmissions are associated with utilization and comorbidity.

OBJECTIVES: Hospital care accounts for up to one-third of the cost of inflammatory bowel disease (IBD) management. A select group of patients with IBD is responsible for a large proportion of this utilization, demonstrating the burden of frequent hospitalizations. We aim to better understand the burden of 30-day readmissions among patients with IBD using a national hospital database. STUDY DESIGN: Retrospective cohort study of state-specific inpatient databases. METHODS: The State Inpatient Databases for New York and Florida were used to identify patients with IBD hospitalized between 2009 and 2013. The prevalence of 30-day IBD-specific readmission was determined. The association between 30-day readmission and visit outcomes, specifically length of stay and a composite of comorbid conditions (venous thromboembolism, pneumonia, sepsis, Clostridium difficile infection, enteral and parenteral nutrition, and blood transfusion), was analyzed using multivariable logistic regression. RESULTS: Patients with IBD accounted for 35,514 and 39,506 inpatient stays in New York and Florida, respectively. Of these stays, 13.7% to 16.2% resulted in a 30-day readmission. On multivariable analysis, 30-day readmissions were associated with a longer length of stay than index hospitalizations by 1.00 day (adjusted regression coefficient, 1.00; 95% CI, 0.73-1.26) and a higher likelihood of having a comorbid condition (adjusted odds ratio, 1.83; 95% CI, 1.68-1.99) in New York. Similar associations were confirmed in Florida. CONCLUSIONS: Nearly 1 in 7 hospitalizations of patients with IBD lead to a 30-day readmission. These IBD-specific readmissions are associated with increased utilization and comorbidity. Patients at risk for readmission need to be targeted to improve outcomes and IBD care quality.

The Use of Actigraphy Differentiates Sleep Disturbances in Active and Inactive Crohn's Disease.

BACKGROUND: Sleep disturbances (SDs) are commonly reported in patients with Crohn's disease (CD). Several survey instruments assessing subjective measures of insufficient sleep have identified SDs in subjects with CD. However, there are limited data on objective measures of SDs in these patients as they relate to disease activity. In this prospective cross-sectional study, we compared objective estimates of sleep obtained using multiday wrist actigraphy in individuals with CD with varying disease activity. METHODS: Eighty patients with a diagnosis of CD were recruited to take part in the study. Participants were stratified by disease activity into remission, mild disease, and moderate to severe disease groups using the Harvey-Bradshaw Index and C-reactive protein levels. Participants were excluded on the basis of significant comorbidity (Charlson Comorbidity Index ≥3), a known history of a sleep disorder, or the concomitant use of systemic corticosteroids. Participants completed surveys, including the PROMIS-SD Short Form 8a, the Epworth Sleepiness Scale, and the Women's Health Initiative Insomnia Rating scale, and were provided with an accelerometer that estimated sleep-wake patterns over 7 days. Comparisons of actigraphic sleep parameters were performed between disease activity groups. Multivariate logistic regression analyses were performed using covariates determined a priori to have an association with sleep disturbance in CD through a review of the literature. RESULTS: Of the 80 participants enrolled in the study, 72 completed 5 days of actigraphy data: 28 subjects in remission, 22 subjects with mild disease activity, and 22 subjects with moderate to severe disease activity. Self-reported sleep characteristics assessed by questionnaires were similar between groups. By actigraphy, individuals with moderate to severe CD spent a significantly longer time awake after falling asleep compared with subjects with remissive disease or compared with subjects with mild disease (65.8 minutes vs 44.3 minutes and 49.1 minutes, respectively; each P < 0.05). Individuals with moderate to severe CD had significantly lower sleep efficiency compared with those with remissive CD (86.6% vs 89.9%; P = 0.03). In the multivariate analyses, moderate to severe CD disease activity was significantly associated with an increased amount of fragmented sleep (odds ratio [OR], 3.70; 95% confidence interval [CI], 1.23-11.32; P = 0.02; WASO ≥ 60 minutes). Moreover, the use of controlled substances was associated with poor sleep efficiency (OR, 3.86; 95% CI, 1.01-14.7; P = 0.04; SE ≤ 85.5%). CONCLUSIONS: This is the first study to objectively quantify disturbed sleep using wrist actigraphy in adults with CD with varying disease activity. Wrist actigraphy may serve as a useful modality for discerning SD in subjects with active vs remissive disease that is not evident with questionnaires alone. Although we determined that disease severity is a significant factor that leads to SDs in CD, larger studies using these objective measures may help determine the contribution of other factors.

Fragmented Care is Prevalent Among Inflammatory Bowel Disease Readmissions and is Associated With Worse Outcomes.

OBJECTIVES: Inflammatory bowel disease (IBD) is a complex chronic disease that often requires a multispeciality approach; thus, IBD patients are prone to care fragmentation. We aim to determine the prevalence of fragmentation among hospitalized IBD patients and identify associated predictors and visit-level outcomes. METHODS: The State Inpatient Databases for New York and Florida were used to identify 90-day readmissions among IBD inpatients from 2009 to 2013. The prevalence of fragmentation, defined as a readmission to a non-index hospital, was reported. Characteristics associated with fragmented care were identified using multivariable logistic regression. Multivariable models were utilized to determine the association between fragmentation and outcomes (in-hospital mortality, readmission length of stay, and inpatient colonoscopy). RESULTS: Among IBD inpatients, 25,241 and 29,033 90-day readmission visits were identified, in New York and Florida, respectively. The prevalence of fragmentation was 26.4% in New York and 32.5% in Florida. Younger age, a non-emergent admission type, public payer or uninsured status, mood disorder, and substance abuse were associated with fragmented care, while female gender and a primary diagnosis of an IBD-related complication had an inverse association. Fragmented inpatient care is associated with a higher likelihood of in-hospital death, higher rates of inpatient colonoscopy, and a longer readmission length of stay. CONCLUSIONS: Over one in four IBD inpatient readmissions are fragmented. Disparities and differences in fragmentation exist and contribute to poor patient outcomes. Additional efforts targeting fragmentation should be made to better coordinate IBD management, reduce healthcare gaps, and promote high-value care.

Abnormal Bolus Reflux Is Associated With Poor Pulmonary Outcome in Patients With Idiopathic Pulmonary Fibrosis.

BACKGROUND/AIMS: Gastroesophageal reflux (GER) is postulated to play a role in idiopathic pulmonary fibrosis (IPF). However, the value of objective GER measures in predicting IPF disease progression is unclear. We aim to evaluate the association between objective GER measures on multichannel intraluminal impedance and pH (MII-pH) testing and development of poor pulmonary outcomes within 1 year in prelung transplant IPF patients. METHODS: This was a retrospective cohort study of adults with IPF who underwent pre-lung transplant evaluation with MII-pH off proton pump inhibitors (PPI) at a tertiary care center from June 2008 to November 2015. Patients were followed for 1 year from time of MII-pH for poor pulmonary outcomes, defined by hospitalization for respiratory exacerbation or death. Univariate, multivariate and time-to-event analyses were performed to assess associations between baseline GER parameters on MII-pH and poor outcomes. RESULTS: Eighty-four subjects (mean age 61.1 years, 64.3% male) were included. Subjects with increased bolus exposure time (BET) had a higher incidence of 1-year poor pulmonary outcome vs normal BET (45.7% vs 15.2%, P = 0.006). Increased BET remained an independent predictor of poor outcome after controlling for age, gender, body mass index, smoking, lung disease severity, and PPI use (OR, 4.18; P = 0.030). Increased BET was also predictive of decreased time to poor pulmonary outcome (hazard ratio [HR], 4.88; P = 0.007). Subgroup analyses showed that increased BET remained independently associated with time to pulmonary hospitalization (HR, 4.00; P = 0.020), with a trend for 1-year mortality (HR, 2.19; P = 0.380). CONCLUSION: Increased BET on MII-pH is an independent predictor of poor pulmonary outcome over 1 year in IPF patients.

The Impact of Opioid Epidemic Trends on Hospitalised Inflammatory Bowel Disease Patients.

BACKGROUND AND AIMS: Opioid use disorder [OUD] has become a public health crisis among patients with chronic disease. Inflammatory bowel disease [IBD] patients are at high risk for OUD because they suffer from chronic relapsing-remitting pain. We aimed to describe the prevalence and trends in OUD-related diagnoses among hospitalised IBD patients. METHODS: A retrospective study was performed using weighted Nationwide Inpatient Sample data from 2005 to 2014. Adult IBD hospital visits and OUD-related diagnoses were identified using a previously published schema. Annual diagnoses were calculated. Characteristics associated with OUD were assessed using multivariable logistic regression. Associations between OUD and length of stay were assessed overall and separately for surgical and non-surgical stays. RESULTS: In all, 2.2% of 2585174 weighted discharges with any diagnosis of IBD also had an OUD-related diagnosis, with an 8.8% average annual increase. In multivariable analysis, Crohn's disease, public payer or no insurance, and psychiatric comorbidities were associated with a higher likelihood of OUD, whereas a primary diagnosis of an IBD-related complication was associated with a lower likelihood. An OUD-related diagnosis was associated with 0.84 days (95% confidence interval [CI] 0.71, 0.97] increased length of stay overall, 2.79 days [95% CI 1.44, 4.14] for surgical stays, and 0.71 days [95% CI 0.59, 0.82] for non-surgical stays. CONCLUSIONS: OUD-related diagnoses are increasing among IBD patients and are associated with increased length of stay. With a rising prevalence, it is important to screen and diagnose OUD in IBD and refer patients for evidence-based treatment to address unmet patient needs and reduce health care utilisation.

Proton Pump Inhibitors Independently Protect Against Early Allograft Injury or Chronic Rejection After Lung Transplantation.

BACKGROUND: Acid reflux has been associated with poor outcomes following lung transplantation. Unlike surgical fundoplication, the role of noninvasive, pharmacologic acid suppression remains uncertain. AIMS: To assess the relationship between post-transplant acid suppression with proton pump inhibitors (PPI) or histamine-2 receptor antagonists (H2RA) and onset of early allograft injury or chronic rejection following lung transplantation. METHODS: This was a retrospective cohort study of lung transplant recipients at a tertiary center in 2007-2014. Patients with pre-transplant antireflux surgery were excluded. Time-to-event analysis using the Cox proportional hazards model was applied to assess acid suppression therapy and onset of acute or chronic rejection, defined histologically and clinically. Subgroup analyses were performed to assess PPI versus H2RA use. RESULTS: A total of 188 subjects (60% men, mean age 54, follow-up 554 person-years) met inclusion criteria. During follow-up, 115 subjects (61.5%) developed rejection, with all-cause mortality of 27.6%. On univariate analyses, acid suppression and BMI, but not other patient demographics, were associated with rejection. The Kaplan-Meier curve demonstrated decreased rejection with use of acid suppression therapy (log-rank p = 0.03). On multivariate analyses, acid suppression (HR 0.39, p = 0.04) and lower BMI (HR 0.67, p = 0.04) were independently predicted against rejection. Subgroup analyses demonstrated that persistent PPI use was more protective than H2RA or no antireflux medications. CONCLUSIONS: Post-lung transplant exposure to persistent PPI therapy results in the greatest protection against rejection in lung transplant recipients, independent of other clinical predictors including BMI, suggesting that PPI may have antireflux or anti-inflammatory effects in enhancing allograft protection.

New Biomarkers for Diagnosing Inflammatory Bowel Disease and Assessing Treatment Outcomes.

Despite advances in our understanding of the pathophysiology underlying inflammatory bowel disease, there remains a significant need for biomarkers that can differentiate between Crohn's disease and ulcerative colitis with high sensitivity and specificity, in a cost-efficient manner. As the focus on personalized approaches to the delivery of medical treatment increases, new biomarkers are being developed to predict an individual's response to therapy and their overall disease course. In this review, we will outline many of the existing and recently developed biomarkers, detailing their role in the assessment of patients with inflammatory bowel disease. We will identify opportunities for improvement in our biomarkers, including better differentiation between the subtypes of inflammatory bowel disease. We will also discuss new targets and strategies in biomarker development, including combining modalities to create biomarker signatures to improve the ability to predict disease courses and response to therapy among individual patients.

Prospective Evaluation of Terminal Ileitis in a Surveillance Population of Patients with Ulcerative Colitis.

BACKGROUND: Ulcerative colitis (UC) is a disease that is normally limited to involvement of the colon. Terminal ileitis in patients with UC with only inactive or mildly active disease has never been investigated. The aim of this prospective study was to determine the prevalence and significance of ileitis among patients with UC enrolled in an endoscopic surveillance program. METHODS: The study consisted of 72 patients with UC and 90 healthy controls who underwent surveillance and screening colonoscopy, respectively. The endoscopic and histologic features of the terminal ileum (both groups) and colon (UC group only) were evaluated in a standardized fashion. Extensive clinical and endoscopic information was obtained from the subjects, and these data were compared between patients with UC either with or without ileitis. RESULTS: Sixteen of 72 patients with UC (22%) had ileitis compared to only 4 of 90 (4%) of the non-UC controls (P < 0.001). None of the patients had features of backwash. Among patients with UC, the presence of ileitis showed a trend towards correlation with extent of disease, but a significant association with involvement of the colonic side of the ileocecal valve (P = 0.02) was noted. Alcohol use in the week before the colonoscopy was also significant (P = 0.02). There were no other features that were significantly related to ileitis in the patients with UC. Only one UC case with ileitis developed Crohn's disease on follow-up. CONCLUSIONS: Ileitis in patients with UC may represent a primary extracolonic manifestation of UC in patients with inactive or mild disease and is not due to backwash.

Reinduction with Certolizumab Pegol in Patients with Crohn's Disease Experiencing Disease Exacerbation: 7-Year Data from the PRECiSE 4 Study.

BACKGROUND: Patients with Crohn's disease in whom tumor necrosis factor antagonist therapy fails have limited treatment options, and the benefit of reintroducing the same therapy remains unclear. Here, we report results from PRECiSE 4 (NCT00160706), an open-label extension study of certolizumab pegol in patients who withdrew from the placebo-controlled studies PRECiSE 1 or 2. METHODS: Patients eligible for PRECiSE 4 had Crohn's disease exacerbation on placebo or primary or secondary failure to certolizumab pegol in PRECiSE 1 or 2, and received 400 mg certolizumab pegol subcutaneously at weeks 0, 2, and 4 and every 4 weeks thereafter up to 360 weeks. We assessed safety (adverse events) and efficacy (clinical remission) of extended certolizumab pegol therapy. RESULTS: Patients enrolled in PRECiSE 4 (N = 310; mean age, 37 yr; 58% female; 95% white) had a mean Crohn's disease duration of 8.5 years before entering the qualifying studies. At weeks 52, 104, and 156, remission rates were 28.5%, 17.5%, and 12.6% by nonremitter imputation, and 63.8%, 60.0%, and 63.5% by observed cases, with 47.4%, 31.9%, and 23.2% of patients, respectively, remaining on therapy. By study end (7.5 yr), 92.3% of patients discontinued therapy, 49% on account of adverse events. No new safety signals emerged. Incidence rate (new cases)/100 patient-years was 6.11 for serious infections and 1.29 for malignancies. CONCLUSIONS: Certolizumab pegol was effective in many patients who previously discontinued certolizumab pegol for lack or loss of response. Thus, discontinuation of therapy may not always be necessary. Safety was consistent with previous findings.

Endoscopic Features and Eosinophil Density Are Associated with Food Impaction in Adults with Esophageal Eosinophilia.

BACKGROUND AND AIMS: Food impaction has been described in both eosinophilic esophagitis and proton pump inhibitor-responsive esophageal eosinophilia. The association between endoscopic/histologic features of esophageal eosinophilia and food impaction remains unclear. We aimed to identify clinical, endoscopic, and histologic findings associated with a history of food impaction in esophageal eosinophilia. METHODS: This was a retrospective cohort study of adult esophageal eosinophilia patients at a tertiary center in 6/2005-10/2014. Only patients with ≥15 eosinophils/high-power field on mucosal biopsies were included. Demographics, comorbidities, symptoms, endoscopic/histologic findings on initial endoscopy, and history of food impaction were reviewed. Statistical analyses were performed using Fisher's exact test (univariate) and forward stepwise logistic regression (multivariate). RESULTS: 400 patients (42 ± 14 years, 61 % male) were included, with 78 (20 %) having food impaction history. On univariate analyses, rings (62 vs 42 %, p = 0.003), erosions (12 vs 5 %, p = 0.03), eosinophil density on biopsy (40 [IQR = 30-50] vs 30 [IQR = 15-50], p = 0.004), and dysphagia (88 vs 62 %, p < 0.0001) were more prevalent among patients with food impaction history, while heartburn (10 vs 33 %, p < 0.0001) and abdominal pain (1 vs 12 %, p = 0.002) were less common. On multivariate analysis, rings (OR 2.6, p = 0.002), erosions (OR 3.2, p = 0.02), and eosinophil density (ß-coefficient = 0.01, p = 0.04) remained associated with food impaction. CONCLUSIONS: Findings of rings and erosions on endoscopy and increased eosinophil density on histology were independently associated with a history of food impaction in adult esophageal eosinophilia patients. Food impaction may result from both active inflammation (erosions and increased eosinophil density) and chronic fibrostenotic changes (rings).

Factors Associated with the Success of In Vitro Fertilization in Women with Inflammatory Bowel Disease.

BACKGROUND: It is unknown whether certain factors are associated with the success of in vitro fertilization (IVF) in women with inflammatory bowel disease (IBD). AIM: This study assessed whether certain characteristics are associated with greater success of live birth following IVF. METHODS: In a cohort study of 8684 women with IBD seen at two tertiary care centers, we identified 121 women with IBD who underwent IVF. We assessed the effect of numerous factors on likelihood of achieving live birth after IVF. RESULTS: Seventy-one patients with ulcerative colitis (UC) and 49 patients with Crohn's disease (CD) were analyzed. Patients with UC who achieved a live birth were younger (p = 0.03), had a shorter duration of disease (p = 0.01), and were more likely to be in remission (p = 0.03) versus those who did not achieve live birth. Patients with CD who achieved live birth were younger (p < 0.001), had lower body mass index (BMI) (p = 0.02), and had lower cycle day 3 follicle-stimulating hormone levels (p = 0.02). There was no difference in likelihood of achieving live birth among patients in remission and those with mild or unknown disease status (p = 0.69), though most CD patients (79.5 %) were in remission. Prior surgery was not associated with live birth in patients with UC (p = 0.31) or CD (p = 0.62). CONCLUSIONS: As in the general infertility population, younger patients and those with lower BMI were more likely to achieve live birth. History of surgery was not associated with live birth among IBD patients. This is important information for practitioners counseling IBD patients.

Prospective evaluation of a simplified narrowband imaging scoring system for a differential diagnosis of colorectal lesions.

BACKGROUND: Narrowband imaging (NBI) allows characterization of colorectal polyps during endoscopy; however, this is underutilized by most US physicians. The aim of this study was to assess diagnostic performance of an NBI scoring system, based on the NBI international colorectal endoscopic classification, and determine a threshold score yielding the highest negative predictive value (NPV) in the characterization of colorectal neoplasia. METHODS: During colonoscopy, colorectal lesions were scored using the NBI scoring system on a 0-3 scale for NBI findings. All lesions were biopsied or endoscopically removed for pathological examinations. RESULTS: Two hundred and three patients were enrolled, and a total of 156 colorectal lesions were detected in 67 patients. Diagnostic yields under white light mode showed limited diagnostic performance [accuracy 75.6 % (68.9-82.3), sensitivity 69.2 % (58.6-78.3), specificity 84.6 % (73.1-92.0), positive predictive value (PPV) 86.3 % (75.8-92.9), NPV 66.3 % (55.0-76.0)]. Of NBI threshold scores from 1 to 3 for the diagnosis of neoplastic lesion, the score of ≥1 resulted in an accuracy of 88.5 % (83.5-93.5), sensitivity of 97.8 % (91.5-96.6), and specificity of 75.4 % (62.9-84.9), with PPV of 84.8 % (76.1-90.8) and NPV of 96.1 % (85.4-99.3). CONCLUSIONS: The threshold value of ≥1 in this simplified NBI scoring system yielded the highest sensitivity and NPV for non-adenomatous colorectal polyps. This scoring system is simple to apply and is superior to white light endoscopy.

Use of blood based biomarkers in the evaluation of Crohn's disease and ulcerative colitis.

Despite significant improvements in our understanding of Crohn's disease (CD) and ulcerative colitis (UC) in recent years, questions remain regarding the best approaches to assessment and management of these chronic diseases during periods of both relapse and remission. Various serologic biomarkers have been used in the evaluation of patients with both suspected and documented inflammatory bowel disease (IBD), and while each has potential utility in the assessment of patients with IBD, potential limitation remain with each method of assessment. Given these potential shortcomings, there has been increased interest in other means of evaluation of patients with IBD, including an expanding interest in the role of gene expression profiling. Among patients with IBD, gene expression profiles obtained from whole blood have been used to differentiate active from inactive CD, as well as to differentiate between CD, UC, and non-inflammatory diarrheal conditions. There are many opportunities for a non-invasive, blood based test to aid in the assessment of patients with IBD, particularly when considering more invasive means of evaluation including endoscopy with biopsy. Furthermore, as the emphasis on personalized medicine continues to increase, the potential ability of gene expression analysis to predict patient response to individual therapies offers great promise. While whole blood gene expression analysis may not completely replace more traditional means of evaluating patients with suspected or known IBD, it does offer significant potential to expand our knowledge of the underlying genes involved in the development of these diseases.

Pre-lung transplant measures of reflux on impedance are superior to pH testing alone in predicting early allograft injury.

AIM: To evaluate pre-lung transplant acid reflux on pH-testing vs corresponding bolus reflux on multichannel intraluminal impedance (MII) to predict early allograft injury. METHODS: This was a retrospective cohort study of lung transplant recipients who underwent pre-transplant combined MII-pH-testing at a tertiary care center from January 2007 to November 2012. Patients with pre-transplant fundoplication were excluded. Time-to-event analysis was performed using a Cox proportional hazards model to assess associations between measures of reflux on MII-pH testing and early allograft injury. Area under the receiver operating characteristic (ROC) curve (c-statistic) of the Cox model was calculated to assess the predictive value of each reflux parameter for early allograft injury. Six pH-testing parameters and their corresponding MII measures were specified a priori. The pH parameters were upright, recumbent, and overall acid reflux exposure; elevated acid reflux exposure; total acid reflux episodes; and acid clearance time. The corresponding MII measures were upright, recumbent, and overall bolus reflux exposure; elevated bolus reflux exposure; total bolus reflux episodes; and bolus clearance time. RESULTS: Thirty-two subjects (47% men, mean age: 55 years old) met the inclusion criteria of the study. Idiopathic pulmonary fibrosis (46.9%) represented the most common pulmonary diagnosis leading to transplantation. Baseline demographics, pre-transplant cardiopulmonary function, number of lungs transplanted (unilateral vs bilateral), and post-transplant proton pump inhibitor use were similar between reflux severity groups. The area under the ROC curve, or c-statistic, of each acid reflux parameter on pre-transplant pH-testing was lower than its bolus reflux counterpart on MII in the prediction of early allograft injury. In addition, the development of early allograft injury was significantly associated with three pre-transplant MII measures of bolus reflux: overall reflux exposure (HR = 1.18, 95%CI: 1.01-1.36, P = 0.03), recumbent reflux exposure (HR = 1.25, 95%CI: 1.04-1.50, P = 0.01) and bolus clearance (HR = 1.09, 95%CI: 1.01-1.17, P = 0.02), but not with any pH-testing parameter measuring acid reflux alone. CONCLUSION: Pre-transplant MII measures of bolus reflux perform better than their pH-testing counterparts in predicting early allograft injury post-lung transplantation.

Efficacy of Vedolizumab as Induction Therapy in Refractory IBD Patients: A Multicenter Cohort.

BACKGROUND: Vedolizumab (VDZ) demonstrated efficacy in Crohn's disease (CD) and ulcerative colitis (UC) in the GEMINI trials. Our aim was to evaluate the efficacy of VDZ at week 14 in inflammatory bowel disease in a multicenter cohort of patients. METHODS: Patients at Massachusetts General Hospital and Brigham and Women's Hospital were considered for inclusion. VDZ (300 mg) was administered at weeks 0, 2, 6, and 14. Efficacy was assessed using the Harvey-Bradshaw index for CD, the simple clinical colitis activity index for UC and physician assessment, along with C-reactive protein and decrease of corticosteroid therapy. Clinical response was defined as decrease in Harvey-Bradshaw index ≥3 and simple clinical colitis activity index ≥3 and remission as Harvey-Bradshaw index ≤4, simple clinical colitis activity index ≤2 and physician assessment of response and remission. RESULTS: Our study included 172 patients (107 CD, 59 UC, 6 inflammatory bowel disease-unclassified, men 48.3%, mean age 40 years and disease duration 14 years). Fourteen patients had ostomy and 9 ileoanal pouch, and only 35.5% fulfilled eligibility for the GEMINI trials. Previous treatment failures with ≥ 2 anti-TNFs occurred in 70.9%, one-third were on an immunomodulator and 46% systemic steroids at baseline. In CD, 48.9% and 23.9% and in UC, 53.9% and 29.3% had clinical response and clinical remission at week 14, respectively. Adverse events occurred in 10.5%. CONCLUSIONS: VDZ is safe and well tolerated in refractory inflammatory bowel disease patients in a clinical practice with efficacy in UC and CD with responses similar to what was seen in clinical trials.

Clinical, pathologic, and outcome study of hyperplastic and sessile serrated polyps in inflammatory bowel disease.

There is evidence that some cancers in patients with inflammatory bowel disease (IBD) develop via the serrated pathway of carcinogenesis. This study examined the clinicopathological features and outcome of 115 IBD patients (65 with ulcerative colitis, 50 with Crohn disease), all with at least 1 serrated polyp at endoscopy or colon resection, including the presence of synchronous and metachronous conventional neoplastic lesions (dysplasia or adenocarcinoma), over an average follow-up period of 56.4 months. Conventional neoplasia was categorized as flat dysplasia (low or high grade), sporadic adenoma, adenoma-like dysplasia-associated lesion or mass, or adenocarcinoma. Overall, 97% of patients had at least 1 hyperplastic polyp (HP), 6% had a sessile serrated adenoma/polyp, and none had a traditional serrated adenoma. Eight patients (7%) had a synchronous conventional neoplastic lesion; only 1 had flat dysplasia (1%) and 2 had adenocarcinoma (2%). Thirteen patients developed a metachronous conventional neoplastic lesion, with 8 developing their conventional neoplasm within an area of previous or concurrent colitis; only 1 patient developed flat dysplasia (1%), and none developed adenocarcinoma. A higher proportion of patients with both an HP and a synchronous conventional neoplastic lesion at index developed a metachronous conventional neoplastic lesion, compared with those with an index HP only (25% versus 7%). These results suggest that IBD patients (both ulcerative colitis and Crohn disease patients) with HP have a very low risk of developing a conventional neoplastic lesion (flat dysplasia or adenocarcinoma) that would warrant surgical resection.