Supratherapeutic Infliximab Levels Do Not Predict Risk of Short-term Complications in Adults With Crohn's Disease.

BACKGROUND: It is uncertain if higher infliximab trough levels (TLs) confer a greater risk of infectious/noninfectious complications (IC/NIC). We aimed to assess the risk of IC and NIC in patients with different TLs. METHODS: We retrospectively evaluated a cohort of Crohn's disease (CD) patients treated with infliximab who underwent therapeutic drug monitoring (TDM), at a tertiary inflammatory bowel disease center, between January 1, 2010, and December 1, 2019. TDM was defined as checking of infliximab trough and antibody levels within a 48-hour period before administration. Patients with a minimum of 3-month assessment pre-TDM and post-TDM were included. In the case of multiple TDMs, the highest TL was considered, and patients were distributed across 4 predefined TL groups (A: <5 µg/mL, B: 5 to 10 µg/mL, C: 10 to 15 µg/mL, and D: ≥15 µg/mL). Rates of IC and NIC during the 3-month prior and following TDM were compared across the groups. In addition, duration of exposure, in terms of months up to TDM, was collected to analyze differences in rates of IC and NIC. RESULTS: Our study included 341 CD patients (median age: 35 y, 58% men). IC and NIC occurred in 52 (15%) and 30 (9%) patients, respectively. Rates of IC and NIC were similar across the 4 TL groups ( P =0.9 and 0.7, respectively for IC and NIC). On multivariable analysis, exposure to infliximab >40 months (as determined by receiver operating characteristic curve analysis) was associated with decreased odds for IC (adjusted odds ratio=0.51, P =0.04), but not NIC (adjusted odds ratio=0.72, P =0.46). CONCLUSIONS: In this large CD cohort, there was no association between infliximab TL and risk of short-term IC or NIC. Interestingly, a shorter duration of exposure predicted higher rates of IC. This supports the safety of targeting higher infliximab TLs when necessary and greater vigilance during the early stages of treatment.

Validation of a Novel Multitarget Blood Test Shows High Sensitivity to Detect Early Stage Hepatocellular Carcinoma.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. Although biannual ultrasound surveillance with or without α-fetoprotein (AFP) testing is recommended for at-risk patients, sensitivity for early stage HCC, for which potentially curative treatments exist, is suboptimal. We conducted studies to establish the multitarget HCC blood test (mt-HBT) algorithm and cut-off values and to validate test performance in patients with chronic liver disease. METHODS: Algorithm development and clinical validation studies were conducted with participants in an international, multicenter, case-control study. Study subjects had underlying cirrhosis or chronic hepatitis B virus; HCC cases were diagnosed per the American Association for the Study of Liver Diseases criteria and controls were matched for age and liver disease etiology. Whole blood and serum were shipped to a central laboratory and processed while blinded to case/control status. An algorithm was developed for the mt-HBT, which incorporates methylation biomarkers (HOXA1, TSPYL5, and B3GALT6), AFP, and sex. RESULTS: In algorithm development, with 136 HCC cases (60% early stage) and 404 controls, the mt-HBT showed 72% sensitivity for early stage HCC at 88% specificity. Test performance was validated in an independent cohort of 156 HCC cases (50% early stage) and 245 controls, showing 88% overall sensitivity, 82% early stage sensitivity, and 87% specificity. Early stage sensitivity in clinical validation was significantly higher than AFP at 20 ng/mL or greater (40%; P < .0001) and GALAD (gender, age, Lens culinaris agglutinin-reactive AFP, AFP, and des-γ-carboxy-prothrombin score) of -0.63 or greater (71%; P = .03), although AFP and GALAD at these cut-off values had higher specificities (100% and 93%, respectively). CONCLUSIONS: The mt-HBT may significantly improve early stage HCC detection for patients undergoing HCC surveillance, a critical step to increasing curative treatment opportunities and reducing mortality. ClinicalTrials.gov number NCT03628651.

A Novel Blood-Based Panel of Methylated DNA and Protein Markers for Detection of Early-Stage Hepatocellular Carcinoma.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) can be treated effectively if detected at an early stage. Recommended surveillance strategies for at-risk patients include ultrasound with or without α-fetoprotein (AFP), but their sensitivity is suboptimal. We sought to develop a novel, blood-based biomarker panel with improved sensitivity for early-stage HCC detection. METHODS: In a multicenter, case-control study, we collected blood specimens from patients with HCC and age-matched controls with underlying liver disease but without HCC. Ten previously reported methylated DNA markers (MDMs) associated with HCC, methylated B3GALT6 (reference DNA marker), and 3 candidate proteins, including AFP, were assayed and analyzed by a logistic regression algorithm to predict HCC cases. The accuracy of the multi-target HCC panel was compared with that of other blood-based biomarkers for HCC detection. RESULTS: The study included 135 HCC cases and 302 controls. We identified a multi-target HCC panel of 3 MDMs (HOXA1, EMX1, and TSPYL5), B3GALT6 and 2 protein markers (AFP and AFP-L3) with a higher sensitivity (71%, 95% CI: 60-81%) at 90% specificity for early-stage HCC than the GALAD score (41%, 95% CI: 30-53%) or AFP ≥7.32 ng/mL (45%, 95% CI: 33-57%). The AUC for the multi-target HCC panel for detecting any stage HCC was 0.92 compared with 0.87 for the GALAD score and 0.81 for AFP alone. The panel performed equally well in important subgroups based on liver disease etiology, presence of cirrhosis, or sex. CONCLUSIONS: We developed a novel, blood-based biomarker panel that demonstrates high sensitivity for early-stage HCC. These data support the potential for liquid biopsy detection of early-stage HCC to clinically benefit at-risk patients. This study was registered on ClinicalTrials.gov (NCT03628651).

Epithelioid Granulomas Associate With Increased Severity and Progression of Crohn's Disease, Based on 6-Year Follow-Up.

BACKGROUND & AIMS: Epithelioid granulomas are characteristics of a subset of patients with Crohn's disease (CD), but their significance, with regard to disease progression and severity, is unclear. We investigated the relationship between granulomas and CD severity over a 6-year time period in a large cohort of patients. METHODS: We performed a retrospective study of patients with CD seen at the Inflammatory Bowel Disease Center at the University of Pittsburgh; data were collected from 2009 through 2014 and patients were assigned to groups with and without histologic evidence of granuloma. Demographic, clinical (including disease activity, quality of life, medication use, and healthcare utilization), and laboratory data were used in association and survival analyses. Differences between groups were evaluated using the Mann-Whitney U-test for continuous variables. RESULTS: Of 1466 patients with CD, granulomas were identified in 187 (12.8%). In the subset of patients who underwent surgery, 21.0% had granulomas. The presence of granuloma was associated with increased serum levels of c-reactive protein (odds ratio [OR], 2.9; 95% CI, 2.078-4.208; P < .0001), younger mean age at diagnosis (23.6 ± 11.3 years in patients with granulomas vs 27.9 ± 13.3 years in patients without; P = .0005), higher rates of stricturing or penetrating disease phenotype, higher rates of steroid and narcotic use, and higher healthcare utilization. Among patients that underwent surgery, the presence of granulomas was associated with need for repeat surgery during the 6-year observation period (OR, 2.5; 95% CI, 1.54-4.02; P = .0002). Infliximab use was associated with detection of granuloma in a significantly lower proportion of surgical specimens compared to patients who had not been treated with a biologic agent (OR, 0.22; 95 CI, 0.05-0.97; P = .03). CONCLUSIONS: Epithelioid granulomas develop in less than 13% of patients with CD, and are associated with a more aggressive disease phenotype. Patients who have undergone surgery for CD and have granulomas are at increased risk for repeat surgery within 6 years.

Endoscopic ultrasound guided 22 gauge core needle biopsy for the diagnosis of Autoimmune pancreatitis.

BACKGROUND: It is difficult to obtain adequate tissue sample for diagnosing autoimmune pancreatitis (AIP) with the help of traditional EUS-guided FNA. As per ICDC guidelines, EUS-guided FNA is not recommended for diagnosing AIP(1). We herein present a report of 2 cases of using a new flexible 22 gauge (G) core biopsy needle (SharkCore, Medtronic, Sunnydale, Calif) for diagnosing AIP. METHODS: This is a report of 2 cases reviewed retrospectively which had used 22G core biopsy needle for obtaining histo-pathological samples for diagnosing AIP. The cases were reviewed with both endoscopist and a pathologist to determine if the diagnostic criteria were met. RESULTS: Both the cases had adequate tissue sample obtained to make a clear diagnosis of AIP. Pathology showed changes of chronic pancreatitis with atrophy and storiform pattern of fibrosis with a dense lymphoplasmacytic infiltrate in both cases along with identification of IgG4 cells. CONCLUSION: EUS-guided fine needle biopsy (FNB) using the SharkCore needle can be used reliably for diagnosing AIP. More studies need to be performed to validate this further.

Differentiation of pancreatic ductal adenocarcinoma from other neoplastic solid pancreatic lesions: a tertiary oncology center experience.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC), pancreatic neuroendocrine tumors (pNET), and metastatic lesions (pMET) are the most common neoplastic solid pancreatic lesions (SPLs). Early diagnosis enables prompt treatment. OBJECTIVE: To identify factors differentiating PDAC from non-PDAC lesions and assess the accuracy of EUS-guided FNA. DESIGN AND SETTING: Retrospective tertiary center. PATIENTS AND INTERVENTION: Consecutive patients referred for EUS evaluation of SPLs from 2004 to 2011. MAIN OUTCOME MEASUREMENTS: Pretest (preceding EUS-guided FNA [EUS-FNA]) predictors of PDAC among neoplastic SPLs and accuracy of EUS-FNA. RESULTS: A total of 1333 EUS scans with 1108 EUS-FNAs were performed for pancreatic lesions. Of the 672 patients with neoplastic SPLs, 528 had PDAC and 144 non-PDAC. The sensitivity, specificity, positive predictive value, and accuracy of EUS-FNA for the diagnosis of PDAC were 97.3%, 99.3%, 99.8%, and 97.8%, respectively. Years of EUS experience significantly correlated with fewer needle passes (Rs = -0.18, P < .001). Controlling for all potential confounders, multivariable regression analysis demonstrated that patients with PDAC compared with pNETs and pMETs were older (odds ratio [OR] 4.42; 95% confidence interval [CI], 2.1-9.5; P < .001), had weight loss (OR 3.0; 95% CI, 1.6-5.4; P < .001), hyperbilirubinemia (OR 3.7; 95% CI, 1.8-7.5; P < .001), elevated CA19-9 (OR 6.9; 95% CI, 2.4-20.3; P < .01), evidence of arterial invasion (OR 6.5; 95% CI, 2.7-15.4; P < .001), and PD dilation (OR 3.3; 95% CI, 1.8-5.9; P < .001). LIMITATIONS: Retrospective design, single center. CONCLUSIONS: When evaluating neoplastic SPLs, demographic, clinical, laboratory, and imaging characteristics can reliably discern and suggest PDAC. In addition, EUS-FNA is exceedingly sensitive and specific for PDAC.

Pretest prediction and diagnosis of metastatic lesions to the pancreas by endoscopic ultrasound-guided fine needle aspiration.

BACKGROUND AND AIM: Early diagnosis of solid pancreatic lesions (SPLs) enables prompt treatment. The study aims to identify factors differentiating metastatic lesion to the pancreas (PMET) from pancreatic ductal adenocarcinoma (PDAC) and pancreatic neuroendocrine tumors (PNETs). METHODS: This is a retrospective study at a tertiary cancer center. Consecutive patients referred for endoscopic ultrasound (EUS) of SPLs from 2004 to 2011 were reviewed. The main outcomes were pre-EUS-FNA (endoscopic ultrasound-guided fine needle aspiration) predictors and diagnostic accuracy of EUS-FNA for PMETs. RESULTS: Among a total of 1108 EUS-FNAs for pancreatic lesions, 672 patients had neoplastic SPLs (PMETs = 53; PDACs = 528, PNETs = 91). The sensitivity, specificity, positive predictive value, and accuracy of EUS-FNA for diagnosis of PMETs were 84.9%, 100%, 100%, and 98.8%, respectively. The mean number of EUS-FNA passes for diagnosis of PMET was 3.1 per patient. For each endosonographer, preceding 3-year EUS volume (mean/year) significantly correlated with fewer needle passes (rs [-0.30], P = 0.03). The most common PMET was renal cell carcinoma. Stratified multivariate analyses were performed. Compared with patients with PDACs, PMETs were more common in men (odds ratio [OR] = 2.0; 95% confidence interval [CI] = 1.0-4.0); located in the pancreatic tail (OR = 2.4; 95%CI = 1.1-5.2); and were less likely with increasing age (OR = 0.95; 95%CI = 0.92-0.99), presence of major symptoms (abdomen pain/diarrhea/weight loss; OR = 0.2; 95%CI = 0.1-0.4), elevated bilirubin (OR = 0.3; 95%CI = 0.13-0.69), and imaging evidence of arterial invasion (OR = 0.15; 95%CI = 0.03-0.67). Compared with PNETs, PMETs were more common with increase age (OR = 1.05; 95%CI = 1.02-1.08) and increasing lesion size (OR = 1.03; 95%CI = 1.0-1.1), and were less likely in patients with diabetes (OR = 0.34; 95%CI = 0.11-0.99). CONCLUSION: Among the largest numbers of neoplastic SPLs evaluated at a single center, pre-test features reliably characterize, and EUS-FNA provides a highly specific diagnosis of PMETs.

Post-closure care of engineered municipal solid waste landfills.

Post-closure care is divided into perpetual care (PPC) and long-term care (LTC). Guidelines for post-closure care and associated costs are important for engineered municipal solid waste (MSW) landfills. In many states in the USA, landfill owners are required to set aside funds for 30-40 years of LTC. Currently there are no guidelines for PPC, which is also required. We undertook a pilot study, using two landfills (note: average landfill capacity 2.5 million MT MSW waste) in Wisconsin, to establish an approach for estimating the LTC period using field data and PPC funding need. Statistical analysis of time versus concentration data of selected leachate parameters showed that the concentration of most parameters is expected to be at or below the preventive action limit of groundwater and leachate volume will be very low, within 40 years of the LTC period. The gas extraction system may need to be continued for more than 100 years. Due to lack of data no conclusion could be made regarding adequacy of the LTC period for the groundwater monitoring system. The final cover must be maintained for perpetuity. The pilot study shows that although technology is available, the financial liability of maintaining a 'Dry Tomb' design for landfills is significantly higher than commonly perceived. The paper will help landfill professionals to estimate realistic post-closure funding and to develop field-based policies for LTC and PPC of engineered MSW landfills.

Next-generation Multi-target Stool DNA Panel Accurately Detects Colorectal Cancer and Advanced Precancerous Lesions.

The multi-target stool DNA (mt-sDNA) test screens for colorectal cancer by analyzing DNA methylation/mutation and hemoglobin markers to algorithmically derive a qualitative result. A new panel of highly discriminant candidate methylated DNA markers (MDM) was recently developed. Performance of the novel MDM panel, with hemoglobin, was evaluated in a simulated screening population using archived stool samples weighted to early-stage colorectal cancer and prospectively collected advanced precancerous lesions (APL). Marker selection study (MSS) and separate preliminary independent verification studies (VS) were conducted utilizing samples from multi-center, case-control studies. Sample processing included targeted MDM capture, bisulfite conversion, and MDM quantitation. Fecal hemoglobin was quantified using ELISA. Samples were stratified into 75%/25% training-testing sets; model outcomes were cross-validated 1,000 times. All laboratory operators were blinded. The MSS included 232 cases (120 colorectal cancer/112 APLs) and 490 controls. The VS featured 210 cases (112 colorectal cancer/98 APLs) and 567 controls; APLs were 86.7% adenomas and 13.3% sessile serrated lesions (SSL). Average age was 65.5 (cases) and 63.2 (controls) years. Mean sensitivity in the VS from cross-validation was 95.2% for colorectal cancer and 57.2% for APLs, with specificities of 89.8% (no CRC/APLs) and 92.4% (no neoplasia). Subgroup analyses showed colorectal cancer sensitivities of 93.4% (stage I) and 94.2% (stage II). APL sensitivity was 82.9% for high-grade dysplasia, 73.4% for villous lesions, 49.8% for tubular lesions, and 30.2% for SSLs. These data support high sensitivity and specificity for a next-generation mt-sDNA test panel. Further evaluation of assay performance will be characterized in a prospective, multi-center clinical validation study (NCT04144738). PREVENTION RELEVANCE: This study highlights performance of the next-generation mt-sDNA test, which exhibits high sensitivity and specificity for detecting colorectal cancer and APLs. This noninvasive option has potential to increase screening participation and clinical outcomes. A multi-center, clinical validation trial is underway. See related commentary by Bresalier, p. 93.

Diagnosis of Inflammatory Bowel Disease-Associated Peripheral Arthritis: A Systematic Review.

BACKGROUND: Inflammatory bowel disease (IBD)-associated peripheral spondyloarthritis (pSpA) decreases quality of life and remains poorly understood. Given the prevalence of this condition and its negative impact, it is surprising that evidence-based disease definitions and diagnostic strategies are lacking. This systematic review summarizes available data to facilitate development and validation of diagnostics, patient-reported outcomes, and imaging indices specific to this condition. METHODS: A literature search was conducted. Consensus or classification criteria, case series, cross-sectional studies, cohort studies, and randomized controlled trials related to diagnosis were included. RESULTS: A total of 44 studies reporting data on approximately 1500 patients with pSpA were eligible for analysis. Data quality across studies was only graded as fair to good. Due to large heterogeneity, meta-analysis was not possible. The majority of studies incorporated patient-reported outcomes and a physical examination. A total of 13 studies proposed or validated screening tools, consensus, classification, or consensus criteria. A total of 28 studies assessed the role of laboratory tests, none of which were considered sufficiently accurate for use in diagnosis. A total of 17 studies assessed the role of imaging, with the available literature insufficient to fully endorse any imaging modality as a robust diagnostic tool. CONCLUSIONS: This review highlights existing inconsistency and lack of a clear diagnostic approach for IBD-associated pSpA. Given the absence of an evidence-based approach, a combination of existing criteria and physician assessment should be utilized. To address this issue comprehensively, our future efforts will be directed toward pursuit of a multidisciplinary approach aimed at standardizing evaluation and diagnosis of IBD-associated pSpA.

This systematic review highlights the lack of an evidence-based approach to the diagnosis of inflammatory bowel disease­associated peripheral spondyloarthritis and the need to standardize evaluation and diagnosis via multidisciplinary collaboration with development of patient-reported outcomes and imaging indices.

An eHealth system supporting palliative care for patients with non-small cell lung cancer: a randomized trial.

BACKGROUND: In this study, the authors examined the effectiveness of an online support system (Comprehensive Health Enhancement Support System [CHESS]) versus the Internet in relieving physical symptom distress in patients with non-small cell lung cancer (NSCLC). METHODS: In total, 285 informal caregiver-patient dyads were assigned randomly to receive, for up to 25 months, standard care plus training on and access to either use of the Internet and a list of Internet sites about lung cancer (the Internet arm) or CHESS (the CHESS arm). Caregivers agreed to use CHESS or the Internet and to complete bimonthly surveys; for patients, these tasks were optional. The primary endpoint-patient symptom distress-was measured by caregiver reports using a modified Edmonton Symptom Assessment Scale. RESULTS: Caregivers in the CHESS arm consistently reported lower patient physical symptom distress than caregivers in the Internet arm. Significant differences were observed at 4 months (P = .031; Cohen d = .42) and at 6 months (P = .004; d = .61). Similar but marginally significant effects were observed at 2 months (P = .051; d = .39) and at 8 months (P = .061; d = .43). Exploratory analyses indicated that survival curves did not differ significantly between the arms (log-rank P = .172), although a survival difference in an exploratory subgroup analysis suggested an avenue for further study. CONCLUSIONS: The current results indicated that an online support system may reduce patient symptom distress. The effect on survival bears further investigation.

The effects of combining Web-based eHealth with telephone nurse case management for pediatric asthma control: a randomized controlled trial.

BACKGROUND: Asthma is the most common pediatric illness in the United States, burdening low-income and minority families disproportionately and contributing to high health care costs. Clinic-based asthma education and telephone case management have had mixed results on asthma control, as have eHealth programs and online games. OBJECTIVES: To test the effects of (1) CHESS+CM, a system for parents and children ages 4-12 years with poorly controlled asthma, on asthma control and medication adherence, and (2) competence, self-efficacy, and social support as mediators. CHESS+CM included a fully automated eHealth component (Comprehensive Health Enhancement Support System [CHESS]) plus monthly nurse case management (CM) via phone. CHESS, based on self-determination theory, was designed to improve competence, social support, and intrinsic motivation of parents and children. METHODS: We identified eligible parent-child dyads from files of managed care organizations in Madison and Milwaukee, Wisconsin, USA, sent them recruitment letters, and randomly assigned them (unblinded) to a control group of treatment as usual plus asthma information or to CHESS+CM. Asthma control was measured by the Asthma Control Questionnaire (ACQ) and self-reported symptom-free days. Medication adherence was a composite of pharmacy refill data and medication taking. Social support, information competence, and self-efficacy were self-assessed in questionnaires. All data were collected at 0, 3, 6, 9, and 12 months. Asthma diaries kept during a 3-week run-in period before randomization provided baseline data. RESULTS: Of 305 parent-child dyads enrolled, 301 were randomly assigned, 153 to the control group and 148 to CHESS+CM. Most parents were female (283/301, 94%), African American (150/301, 49.8%), and had a low income as indicated by child's Medicaid status (154/301, 51.2%); 146 (48.5%) were single and 96 of 301 (31.9%) had a high school education or less. Completion rates were 127 of 153 control group dyads (83.0%) and 132 of 148 CHESS+CM group dyads (89.2%). CHESS+CM group children had significantly better asthma control on the ACQ (d = -0.31, 95% confidence limits [CL] -0.56, -0.06, P = .011), but not as measured by symptom-free days (d = 0.18, 95% CL -0.88, 1.60, P = 1.00). The composite adherence scores did not differ significantly between groups (d = 1.48%, 95% CL -8.15, 11.11, P = .76). Social support was a significant mediator for CHESS+CM's effect on asthma control (alpha = .200, P = .01; beta = .210, P = .03). Self-efficacy was not significant (alpha = .080, P = .14; beta = .476, P = .01); neither was information competence (alpha = .079, P = .09; beta = .063, P = .64). CONCLUSIONS: Integrating telephone case management with eHealth benefited pediatric asthma control, though not medication adherence. Improved methods of measuring medication adherence are needed. Social support appears to be more effective than information in improving pediatric asthma control. TRIAL REGISTRATION: Clinicaltrials.gov NCT00214383; http://clinicaltrials.gov/ct2/show/NCT00214383 (Archived by WebCite at http://www.webcitation.org/68OVwqMPz).

A United States expert consensus to standardise definitions, follow-up, and treatment targets for extra-intestinal manifestations in inflammatory bowel disease.

BACKGROUND AND AIMS: Extra-intestinal manifestations (EIMs) are a common complication of inflammatory bowel diseases (IBD), affecting up to half of the patients. Despite their high prevalence, information on standardised definitions, diagnostic strategies, and treatment targets is limited. METHODS: As a starting point for a national EIM study network, an interdisciplinary expert panel of 12 gastroenterologists, 4 rheumatologists, 3 ophthalmologists, 6 dermatologists, and 4 patient representatives was assembled. Modified Delphi consensus methodology was used. Fifty-four candidate items were derived from the literature review and expert opinion focusing on five major EIMs (erythema nodosum, pyoderma gangrenosum, uveitis, peripheral arthritis, and axial arthritis) were rated in three voting rounds. RESULTS: For use in a clinical practice setting and as part of the creation of a prospective registry of patients with EIMs, the panel developed definitions for erythema nodosum, pyoderma gangrenosum, uveitis, peripheral arthritis, and axial arthritis; identified the appropriate and optimal subspecialists to diagnose and manage each; provided methods to monitor disease course; offered guidance regarding monitoring intervals; and defined resolution and recurrence. CONCLUSIONS: Consensus criteria for appropriate and optimal means of diagnosing and monitoring five EIMs have been developed as a starting point to inform clinical practice and future trial design. Key findings include straightforward diagnostic criteria, guidance regarding who can appropriately and optimally diagnose each, and monitoring options that include patient and physician-reported outcomes. These findings will be used in a national multicenter study network to optimise the management of EIMs.

Endpoints for extraintestinal manifestations in inflammatory bowel disease trials: the EXTRA consensus from the International Organization for the Study of Inflammatory Bowel Diseases.

Extraintestinal manifestations occur frequently in patients with inflammatory bowel disease (IBD) and remain a diagnostic and therapeutic challenge. The aim of the Endpoints for Extraintestinal Manifestations in Inflammatory Bowel Disease Trials (EXTRA) initiative was to achieve international expert consensus on how to assess these manifestations in IBD trials. A systematic literature review was done to identify methods to diagnose extraintestinal manifestations in patients with IBD and measure treatment outcomes. A consensus meeting involving a panel of 41 attendees, including gastroenterologists and referral specialists, was held on March 31, 2021, as part of an International Organization for the Study of Inflammatory Bowel Diseases initiative. The panel agreed that a specialist's expertise is needed to confirm the diagnosis of extraintestinal manifestations before the inclusion of a patient in IBD trials, except for axial spondyloarthritis, for which typical symptoms and MRI can be sufficient. Easy-to-measure endpoints were identified to assess the response of extraintestinal manifestations to treatment without needing specialist involvement. For uveitis, peripheral spondyloarthritis, and arthralgia, endpoint measurements need specialist expertise. The timing of endpoint measurements was discussed for individual extraintestinal manifestations. The EXTRA consensus proposes guidelines on how to thoroughly evaluate extraintestinal manifestations within IBD trials, and recommends that these guidelines are implemented in future trials to enable prospective assessment of these manifestations and comparison between studies.

Using action research to implement an integrated pediatric asthma case management and eHealth intervention for low-income families.

Asthma case management and education programs improve pediatric asthma outcomes, but designing rigorous randomized controlled studies that accurately measure effects while encouraging parent participation is challenging. This is especially so for low-income African American families, who face significantly more severe asthma and social stress than their middle-class counterparts. Action research can help health education researchers negotiate between the elegant and complex designs favored by scientists with the real-life challenges of recruitment, implementation, and retention. This article discusses how a multidisciplinary team uses action research concepts to continuously adjust originally proposed protocols through the planning and implementation phases to encourage participation in a year-long randomized controlled trial of a program that combines telephone asthma case management and comprehensive online asthma education. As a result of these efforts, a higher proportion of low-income African American families are recruited into the study than originally proposed.

Biologic Therapy for Ulcerative Colitis.

Five biologics are approved for the treatment of ulcerative colitis (UC): infliximab, adalimumab, golimumab, vedolizumab, and ustekinumab. These drugs have varying levels of efficacy and are recommended as first-line treatment of moderate to severe UC. There has been only 1 head-to-head trial comparing the efficacy of the biologics, adalimumab and vedolizumab, which has important implications for management. Therapeutic drug monitoring of biologics, especially anti-TNF alpha agents, may improve the long-term efficacy of these agents. The future of treatment may include personalization of medications, based on patient-specific and disease-specific characteristics as well as biomarkers, along with appropriate therapeutic drug monitoring.

Vedolizumab Serum Trough Concentrations and Response to Dose Escalation in Inflammatory Bowel Disease.

Serum vedolizumab concentrations are associated with clinical response although, it is unknown if vedolizumab concentrations predict response to dose escalation. The aim of this study was to identify if vedolizumab trough concentrations predicted the response to vedolizumab dose escalation. We assessed a retrospective cohort of patients on maintenance vedolizumab dosing at five tertiary care centers with vedolizumab trough concentrations. Multivariate logistic regression was used to control for potential confounders of association of vedolizumab concentration and clinical status. Those who underwent a dose escalation were further examined to assess if vedolizumab trough concentration predicted the subsequent response. One hundred ninety-two patients were included. On multivariate analysis, vedolizumab trough concentration (p = 0.03) and the use of immunomodulator (p = 0.006) were associated with clinical remission. Receiver operator curve analysis identified a cut off of 7.4 µg/mL for clinical remission. Of the fifty-eight patients with dose escalated, 74% of those with a vedolizumab concentration <7.4 µg/mL responded versus 52% of those with a vedolizumab trough concentration ≥7.4 µg/mL (p = 0.08). After adjustment for relevant confounders, the odds ratio for response with vedolizumab concentration <7.4 µg/mL was 3.7 (95% CI, 1.1-13; p = 0.04). Vedolizumab trough concentration are associated with clinical status and can identify individuals likely to respond to dose escalation. However, a substantial portion of patients above the identified cut off still had a positive response. Vedolizumab trough concentration is a potentially helpful factor in determining the need for dose escalation in patients losing response.

Endoscopy in Postoperative Patients with Crohn's Disease or Ulcerative Colitis. Does It Translate to Better Outcomes?

This article discusses the use of endoscopy in patients with Crohn disease and ulcerative colitis in the postoperative setting. Endoscopy is the most sensitive and validated tool available in the diagnosis of recurrence of Crohn disease in the postoperative setting. It is also the most effective diagnostic modality available for evaluating complications of pouch anatomy in patients with ulcerative colitis. In addition to diagnosis, management postoperatively can be determined through endoscopy.