The Real-World Effectiveness and Safety of Ustekinumab in the Treatment of Crohn's Disease: Results From the SUCCESS Consortium.

INTRODUCTION: We evaluated the real-world effectiveness and safety of ustekinumab (UST) in patients with Crohn's disease (CD). METHODS: This study used a retrospective, multicenter, multinational consortium of UST-treated CD patients. Data included patient demographics, disease phenotype, disease activity, treatment history, and concomitant medications. Cumulative rates of clinical, steroid-free, endoscopic, and radiographic remissions were assessed using time-to-event analysis, and clinical predictors were assessed by using multivariate Cox proportional hazard analyses. Serious infections and adverse events were defined as those requiring hospitalization or treatment discontinuation. RESULTS: A total of 1,113 patients (51.8% female, 90% prior antitumor necrosis factor exposure) were included, with a median follow-up of 386 days. Cumulative rates of clinical, steroid-free, endoscopic, and radiographic remissions at 12 months were 40%, 32%, 39%, and 30%, respectively. Biologic-naive patients achieved significantly higher rates of clinical and endoscopic remissions at 63% and 55%, respectively. On multivariable analyses, prior antitumor necrosis factor (hazard ratio, 0.72; 95% confidence interval, 0.49-0.99) and vedolizumab exposure (hazard ratio, 0.65; 95% confidence interval, 0.48-0.88) were independently associated with lower likelihoods of achieving endoscopic remission. In patients who experienced loss of remission, 77 of 102 (75%) underwent dose optimization, and 44 of 77 (57%) achieved clinical response. An additional 152 of 681 patients (22.3%) were dose-optimized because of primary nonresponse incomplete response to UST, of whom 40.1% (61 of 152) responded. Serious infections occurred in 3.4% of patients while other noninfectious adverse events (lymphoma [n = 1], arthralgia [n = 6], rash [n = 6], headache [n = 3], hepatitis [n = 3], hair loss [n = 3], neuropathy [n = 1], and vasculitis [n = 1]) occurred in 2.4% of patients. DISCUSSION: UST represents a safe and effective treatment option for CD, with 40% of patients from a highly refractory cohort achieving clinical remission by 12 months. The greatest treatment effect of UST was seen in biologic-naive patients, and dose escalation may recapture clinical response.

De Novo Ostomy Placement Is Associated with Increased Outpatient Opioid Use In Patients with Inflammatory Bowel Disease.

BACKGROUND/AIMS: Opioid use is associated with poor outcomes in patients with inflammatory bowel disease (IBD). We aimed to identify novel factors associated with increased outpatient opioid (OPRx) use following IBD-related hospitalization. METHODS: This was a retrospective cohort study of IBD patients ≥ 18 years old, hospitalized during 2018. The primary outcome was receiving ≥ 1(OPRx) in the year following index hospitalization (IH), excluding prescriptions written within 2 weeks of discharge. Secondary outcomes included having 1-2 vs ≥ 3 OPRx and rates of healthcare utilization. Univariate and multivariate analyses tested associations with OPRx. RESULTS: Of 526 patients analyzed, 209 (40%) received at least 1 OPRx; with a median of 2 [1-3] OPRx. Presence or placement of ostomy at IH, exposure to opioids during IH, ulcerative colitis (UC), mental health comorbidities, admission for surgery and managed on the surgical service, and IBD surgery within 1 year prior to IH were associated with ≥ 1 OPRx on univariate analysis. On multivariable analysis, UC, ostomy placement during IH, anxiety, and inpatient opioid exposure were independently associated with ≥ 1 OPRx. A majority (> 70%) of both inpatient and outpatient opioid prescriptions were written by surgeons. Patients requiring ≥ 3 OPRx had the highest rates of unplanned IBD surgery (56% p = 0.04), all-cause repeat hospitalization (81%, p = 0.003), and IBD-related repeat hospitalization (77%, p = 0.007) in the year following IH. CONCLUSIONS: A multimodal approach to pain management for IBD patients, as well as increased recognition that any patient with a de novo ostomy is at particular risk of opioid use, is needed.

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.

Delays in Initiating Post-operative Prophylactic Biologic Therapy Are Common Among Crohn's Disease Patients.

BACKGROUND: Studies have shown that prophylactic biologic therapy can reduce post-surgical Crohn's disease recurrence. AIMS: We aimed to identify the frequency of delay and risk factors associated with a delay in the initiation of prophylactic post-surgical biologic therapy in high-risk patients. METHODS: We performed a cohort study of Crohn's disease patients who underwent a bowel resection. We identified those at risk of recurrence and explored multiple characteristics for those with and without a delay post-operatively. RESULTS: A total of 84 patients were included in our analysis of which 69.0% had a greater than 4-week delay and 56.0% a greater than 8-week delay in post-surgical biologic prophylaxis. Publicly insured patients had a 100% delay in post-surgical prophylaxis initiation (p = 0.039, p = 0.003 at 4 and 8 weeks, respectively). Patients on a biologic pre-surgery were less likely to have a delay (p < 0.001) in post-operative prophylaxis. Care at an inflammatory bowel disease (IBD) center was associated with timely therapy when considering a post-operative immunomodulator or biologic strategy. CONCLUSIONS: There are a substantial number of delays in initiating post-operative prophylactic biologic therapy in high-risk patients. Identifying susceptible patients by insurance type or absence of pre-operative therapy can focus future improvement efforts. Additionally, consultation with IBD-specialized providers should be considered in peri-surgical IBD care.

Risk of Early Colorectal Cancers Needs to Be Considered in Inflammatory Bowel Disease Care.

BACKGROUND: Current guidelines recommend starting colorectal cancer (CRC) surveillance 8-10 years after inflammatory bowel disease (IBD) onset. Recent studies report that the incidence of CRC within 8-10 years of IBD onset (i.e., early CRC) ranges from 12 to 42%. AIMS: To describe the current prevalence of early CRC in a tertiary care center IBD cohort with CRC and to identify associated risk factors. METHODS: We performed a single-center observational study of IBD patients diagnosed with CRC from 2005 to 2015. We compared characteristics of patients with early CRC (diagnosis of CRC within 8 years of initial IBD onset) to those with CRC diagnosed later in their IBD course. RESULTS: Ninety-three patients met inclusion criteria. Eleven (11.8%) patients developed CRC within 8 years of initial IBD onset. On multivariable logistic regression, age greater than 28 at IBD onset (adjusted OR 12.0; 95% CI 2.30, 62.75) and tobacco use (adjusted OR 8.52; 95% CI 1.38, 52.82) were significant predictors of early CRC. A validation cohort confirmed calibration and discrimination of the model. CONCLUSIONS: One out of every eight IBD patients with CRC developed their malignancy prior to the currently recommended timeframe for the initiation of surveillance colonoscopy. IBD onset at 28 years or older and tobacco use were identified as predictors of early CRC. Early CRC should be considered in discussions of cancer surveillance in this population. Prospective cohort studies are necessary to further analyze the impact of early CRC in IBD.

MR Imaging of Adverse Local Tissue Reactions around Rejuvenate Modular Dual-Taper Stems.

PURPOSE: To describe the magnetic resonance (MR) imaging characteristics associated with adverse local tissue reactions and tissue damage around hip arthroplasties in which the recalled Rejuvenate modular dual-taper stem was used. MATERIALS AND METHODS: The institutional review board of the Hospital for Special Surgery approved the study. All study patients provided informed consent. MR imaging studies were retrospectively reviewed in a cohort of 58 patients with 66 hip arthroplasties with Rejuvenate stems who had presented for imaging evaluation because of recall of the implant. Multiple regression analysis was used to examine MR imaging features, biomechanical factors, and metal ion levels as predictors of aseptic lymphocytic vasculitis-associated lesion (ALVAL) score at histologic assessment while adjusting for age and sex for 54 revised hips. RESULTS: Revision surgery was performed in 54 hips on the basis of clinical or imaging findings (24% of hips were completely asymptomatic). The median ALVAL score among the revised hips was 9 (range, 1-10). Imaging characteristics observed with high frequency in patients with ALVAL included synovitis, mixed- or solid-type synovitis, synovial thickening, and capsular dehiscence. CONCLUSION: MR imaging provides an effective noninvasive method for assessing the presence and severity of adverse local tissue reaction, as well as the degree of pre-existing tissue damage, thereby facilitating early and accurate identification of candidates for revision surgery.

Therapeutic alliance in the personal therapy of graduate clinicians: relationship to the alliance and outcomes of their patients.

UNLABELLED: This is the first study to explore the relationship between aspects of a therapists' personal therapy and the subsequent psychotherapy process and outcome they perform. The participants were 14 graduate clinicians with various experiences in personal therapy, who treated 54 outpatients engaged in short-term psychodynamic psychotherapy at a university-based community clinic. Results demonstrated non-significant relationships between the duration of personal therapy as well as a graduate clinician's overall alliance in their personal therapy with alliance ratings made by themselves as therapists and their patients, as well as the number of psychotherapy sessions attended by patients. However, the clinician's personal therapy alliance was significant and positively related to their patients' rating of outcome. Additionally, a significant negative correlation was observed between the degree of perceived helpfulness in their personal therapy and how these clinicians rated alliances, as the therapist, with their patients. The current findings suggest a relationship between a clinician's personal therapy alliance and the outcome of treatments they conduct. Implications for clinical training and practice as well as future research are discussed. KEY PRACTITIONER MESSAGE: While graduate clinician's personal therapy alliance was not significantly related to their patients' ratings of alliance, it was related to their patients' ratings of outcome. Trainee satisfaction with or quality of their personal therapy may be a more relevant than the amount or duration of their treatment in regard to the process and outcomes of their patients. The findings from retrospective clinician surveys on the helpfulness of their personal therapy may not be entirely consistent with empirical examination of these issues. The relation of personal therapy and outcome may work through improving the therapist's level of adaptive functioning (i.e., psychological-relational-emotional health) and future research should examine this simpler, more parsimonious, explanation for our findings.

MRI predicts ALVAL and tissue damage in metal-on-metal hip arthroplasty.

BACKGROUND: Adverse local tissue reactions (ALTR) around metal-on-metal (MOM) hip arthroplasties are increasingly being recognized as a cause of failure. These reactions may be associated with intraoperative tissue damage and complication rates as high as 50% after revision. Although MRI can identify ALTR in MOM hips, it is unclear whether the MRI findings predict those at revision surgery. QUESTIONS/PURPOSES: We therefore (1) identified which MRI characteristics correlated with histologically confirmed ALTR (using the aseptic lymphocytic vasculitis-associated lesions [ALVAL] score) and intraoperative tissue damage and (2) developed a predictive model using modified MRI to detect ALVAL and quantify intraoperative tissue damage. METHODS: We retrospectively reviewed 68 patients with failed MOM hip arthroplasties who underwent preoperative MRI and subsequent revision surgery. Images were analyzed to determine synovial volume, osteolysis, and synovial thickness. The ALVAL score was used to grade tissue samples, thus identifying a subset of patients with ALTR. Intraoperative tissue damage was graded using a four-point scale. Random forest analysis determined the sensitivity and specificity of MRI characteristics in detecting ALVAL (score ≥ 5) and intraoperative tissue damage. RESULTS: Maximal synovial thicknesses and synovial volumes as determined on MRI correlated with the ALVAL score and were higher in cases of severe intraoperative tissue damage. Our MRI predictive model showed sensitivity and specificity of 94% and 87%, respectively, for detecting ALVAL and 90% and 86%, respectively, for quantifying intraoperative tissue damage. CONCLUSIONS: MRI is sensitive and specific in detecting ALVAL and tissue damage in patients with MOM hip implants. MRI can be used as a screening tool to guide surgeons toward timely revision surgery.

The use of parenteral nutrition in patients with inflammatory bowel disease: A detailed guide on the indications, risks, and benefits.

Malnutrition is estimated to affect roughly 30%-80% of patients with inflammatory bowel disease (IBD). In those patients who cannot tolerate sufficient oral nutrition or there is no possibility for placing an enteral nutrition tube, parenteral nutrition offers a lifesaving alternative. However, this is not without risk. For patients with IBD, understanding the indications, contraindications, and complications associated with parenteral nutrition is crucial. In this review, we will discuss the indications and contraindications for parenteral nutrition in patients with IBD, the common complications associated with intravenous nutrition, the use of parenteral nutrition in special populations, such as in pediatric and perioperative patients, and the impact of parenteral nutrition on IBD-related outcomes.

Magnetic resonance imaging of the wrist: bone and cartilage injury.

Magnetic resonance imaging (MRI) is particularly useful for imaging the wrist due to its superior soft tissue contrast and ability to detect subtle bone marrow changes and occult fractures. A high field (1.5T or greater) strength, dedicated wrist coil, and high in-plane and through-plane resolution must be utilized to successfully visualize the relatively thin cartilage of the wrist. MRI can be used to detect occult carpal bone fractures, identify complications following scaphoid fractures, and assess for avascular necrosis in the setting in Kienböck's and Preiser's disease. MRI is useful to identify secondary soft tissue and chondral pathology in impaction/impingement syndromes. The use of an intermediate-echo time fast spin echo sequence allows for accurate assessment of articular cartilage, allowing evaluation of chondral wear in the setting of primary osteoarthritis and posttraumatic degenerative arthrosis. MRI is the most sensitive imaging modality for the detection of early inflammatory arthropathies and can detect synovitis, bone marrow edema, and early erosions in the setting of negative radiographs.

Assessment of reactive synovitis in rotating-platform posterior-stabilized design: a 10-year prospective matched-pair MRI study.

This is the first long-term (mean 11.6 years), prospective, matched-pair study (based on age, gender, BMI and UCLA scores) using MAVRIC (multi-acquisition variable-resonance image combination) magnetic resonance imaging to analyze reactive synovitis and osteolysis between rotating-platform posterior-stabilized (RP-PS), fixed-bearing metal-back (FB-MB), and all-polyethylene tibial (APT) in active patients (24 total, 8 in each group, mean age of 64 years, mean UCLA of 8.5) with identical femoral component and polyethylene. Reactive synovitis was observed in 6 RP-PS (75%), all 8 FB-MB (100%), and 6 APT (75%). There was a significant difference between the RP-PS and FB-MB knees in volumetric synovitis (P=0.023). Osteolysis with bone loss more than 4mm was seen in 3 FB-MB, 2 APT and none for RP-PS. These were not statistically significant.

To Fiber or Not to Fiber: The Swinging Pendulum of Fiber Supplementation in Patients with Inflammatory Bowel Disease.

Evidence-based dietary guidance around dietary fiber in inflammatory bowel disease (IBD) has been limited owing to insufficient reproducibility in intervention trials. However, the pendulum has swung because of our increased understanding of the importance of fibers in maintaining a health-associated microbiome. Preliminary evidence suggests that dietary fiber can alter the gut microbiome, improve IBD symptoms, balance inflammation, and enhance health-related quality of life. Therefore, it is now more vital than ever to examine how fiber could be used as a therapeutic strategy to manage and prevent disease relapse. At present, there is limited knowledge about which fibers are optimal and in what form and quantity they should be consumed to benefit patients with IBD. Additionally, individual microbiomes play a strong role in determining the outcomes and necessitate a more personalized nutritional approach to implementing dietary changes, as dietary fiber may not be as benign as once thought in a dysbiotic microbiome. This review describes dietary fibers and their mechanism of action within the microbiome, details novel fiber sources, including resistant starches and polyphenols, and concludes with potential future directions in fiber research, including the move toward precision nutrition.

Review article: Putting some muscle into sarcopenia-the pathogenesis, assessment and clinical impact of muscle loss in patients with inflammatory bowel disease.

BACKGROUND: Sarcopenia, a loss of skeletal muscle mass or function, affects up to 50% of patients with inflammatory bowel disease (IBD) and is associated with poor clinical outcomes including increased hospitalizations, need for surgery and post-operative complications. Despite the high prevalence and clinical significance of sarcopenia in patients with IBD, few patients undergo routine muscle evaluation. AIM: The goal of this study was to review the mechanisms of sarcopenia in patients with IBD and understand novel modalities to assess and treat impaired muscle mass or function. METHODS: Pubmed and Cochrane databases were searched including articles published up to February 2023 utilizing the following keywords: "inflammatory bowel disease", "IBD", "Crohn's disease", "ulcerative colitis", "sarcopenia", "myosteatosis", "muscle health", and "frailty". RESULTS: The pathogenesis of sarcopenia in IBD is not well defined, however, there is evidence supporting the role of malabsorption, reduced protein intake, chronic inflammation, dysbiosis, decreased physical activity, medication effects and hormone signaling from visceral adiposity. Traditional sarcopenia assessment techniques include direct measurements on cross sectional imaging. However, given the time, cost and radiation exposure associated with cross sectional imaging, new bedside tools are now available to estimate muscle mass, including assessment of grip strength, mid upper arm circumference and body composition utilizing bioelectrical impedance analysis. In addition, novel biomarkers for assessing muscle mass and techniques utilizing point of care ultrasound have been proposed to make sarcopenia evaluation more streamlined in the IBD clinic. CONCLUSION: Sarcopenia is associated with poor clinical outcomes independent of IBD activity and therefore muscle health should be assessed in all IBD patients at routine intervals. Future studies to better our understanding of the pathophysiology as well as most effective management of sarcopenia in IBD will help guide clinical care and reduce disease related complications.

Identification and Evaluation of Mobile Applications for Self-Management of Diet and Lifestyle for Patients with Inflammatory Bowel Disease.

Background: Mobile health applications (apps) providing diet and lifestyle self-management programs to patients with inflammatory bowel disease (IBD) are emerging. The objective of this study was to evaluate current apps available in the US and Canada based on app quality, perceived impact on diet and mental health and comprehensiveness to support self-management. Methods: The Apple iOS and Google Play app stores were searched for terms related to IBD. Apps were included if they targeted diet and lifestyle behaviours for patients living with IBD and were available to the general public. Apps were excluded if they were not specific to IBD, not available in English, did not target diet or lifestyle therapy, were not available in the US and Canada, or did not offer stand-alone self-management programs. The Mobile App Rating Scale was used to assess mobile app quality. Results: A total of 1,512 apps were identified through the app stores. Six apps met inclusion criteria. My IBD Care: Crohn's and Colitis received the highest quality rating and LyfeMD received the highest overall app rating. Only these two apps provided behaviour tracking over time, and three (50 percent) apps provided good-quality information. Conclusions: While many IBD-related apps exist, few support self-management of diet and lifestyle behaviours. The My IBD Care and LyfeMD apps had the highest ratings and can be used to track lifestyle behaviours. The effectiveness of these apps to improve behaviours, and subsequently impact the disease course and quality of life, should be explored in future studies.

High Prevalence of Malnutrition and Micronutrient Deficiencies in Patients With Inflammatory Bowel Disease Early in Disease Course.

BACKGROUND: Patients with inflammatory bowel disease (IBD) are at an increased risk of malnutrition. The goal of this study was to define the prevalence of malnutrition and micronutrient deficiencies in recently diagnosed IBD patients and to compare the performance of existing malnutrition screening tools in identifying IBD patients at increased risk for malnutrition. METHODS: This was a retrospective cohort study of adult patients with recently diagnosed IBD (≤18 months disease duration). A diagnosis of malnutrition was made utilizing the European Society for Clinical Nutrition and Metabolism malnutrition criteria. Serum micronutrient levels were included. The sensitivity of 5 malnutrition screening tools in identifying patients at moderate-high risk of malnutrition was determined based on the European Society for Clinical Nutrition and Metabolism malnutrition definition. Descriptive statistics summarized the data and univariate analyses tested associations. RESULTS: A total of 182 patients were included for analysis; 65 (36%) met criteria for malnutrition. A total of 135 (74%) patients had ≥1 micronutrient level checked and 105 (78%) had ≥1 deficiency. Patients with prior surgery (odds ratio [OR], 4.5; P = .004), active Crohn's disease (OR, 2.8; P = .03), and diarrhea (OR, 2.1; P = .02) were more likely to be malnourished. The Malnutrition Universal Screening Tool and Saskatchewan IBD Nutrition Risk Tool had the highest sensitivity (100%) in predicting those at moderate-high risk of malnutrition at the time of screening. CONCLUSIONS: Patients with recently diagnosed IBD have a high prevalence of malnutrition and micronutrient deficiencies. Both the Malnutrition Universal Screening Tool and Saskatchewan IBD Nutrition Risk Tool can be used to identify those at increased risk of malnutrition. Future studies and screening tool development are necessary to identify those at risk of developing malnutrition to facilitate timely referral for nutritional evaluation and prevent disease related complications.

This retrospective cohort study identified that patients with recently diagnosed inflammatory bowel disease have a high prevalence of malnutrition as well as micronutrient deficiencies and compared the utility of 5 available malnutrition screening tools in this population.