Optimal Management of Refractory Crohn's Disease: Current Landscape and Future Direction.

Refractory Crohn's disease, defined as ongoing inflammation despite the trial of multiple advanced therapies, impacts a number of individuals with Crohn's disease, and leads to significant burden in quality of life and cost. Interventions such as early implementation of advanced therapies, optimization of current therapies prior to switching to an alternative, as well as understanding the overlapping pathophysiology between immune-mediated disorders, however, can help shift the current landscape and reduce the number of patients with refractory disease. As such, in this review we summarize the key takeaways of the latest research in the management of moderate-to-severe Crohn's disease, focusing on maximization of our currently available medications, while also exploring topics such as combination advanced therapies. We also describe evidence for emerging and alternative therapeutic modalities, including fecal microbiota transplant, exclusive enteral feeding, hyperbaric oxygen, stem cell therapy, bone marrow transplant, and posaconazole, with a focus on both the potential impact and specific indications for each.

Older Adults With Inflammatory Bowel Disease Are at Higher Risk of Developing Antibodies to Infliximab.

Although older age is thought to confer immunosenescence, we found that older adults with inflammatory bowel disease are independently at higher risk to develop antibodies to infliximab. Additionally, older adults are less likely to receive escalated doses of infliximab.

Impact of Biologics and Small-Molecule Agents on Postoperative Complications in IBD: A Systematic Review.

BACKGROUND: Patients with IBD may require colectomy for severe disease unresponsive or refractory to pharmacological therapy. The question of the impact of biologic use on postoperative complications is a topic of active investigation. OBJECTIVE: A systematic literature review was performed to describe the current state of knowledge of the impact of perioperative biologic and tofacitinib use on postoperative complications in patients with IBD. DATA SOURCES: PubMed and Cochrane databases were searched. STUDY SELECTION: Studies between January 2000 and January 2023, in any language, were searched, followed by a snowball search identifying further studies in accordance with Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. Articles regarding pediatric or endoscopic management were excluded. INTERVENTIONS: Preoperative or perioperative exposure to biologics in IBD was included. MAIN OUTCOME MEASURES: Infectious and noninfectious complications, including anastomotic leaks, surgical site infections, urinary tract infections, pneumonia, sepsis, septic shock, postoperative length of stay, readmission, and reoperation, were the main outcomes measured. RESULTS: A total of 28 studies were included for analysis in this review, including 7 meta-analyses or systematic reviews and 5 randomized studies. Snowball search identified 11 additional studies providing topical information. Overall, tumor necrosis factor inhibitors likely do not increase the risk of postoperative adverse outcomes, while data on other biologics and small-molecule agents are emerging. LIMITATIONS: This is a qualitative review including all study types. The varied nature of study types precludes quantitative comparison. CONCLUSIONS: Although steroids increase postoperative infectious and noninfectious complications, tumor necrosis factor inhibitors do not appear to increase postoperative infectious and noninfectious complications. There is a need for further perioperative data for other agents. See video from symposium .

Structured deep embedding model to generate composite clinical indices from electronic health records for early detection of pancreatic cancer.

The high-dimensionality, complexity, and irregularity of electronic health records (EHR) data create significant challenges for both simplified and comprehensive health assessments, prohibiting an efficient extraction of actionable insights by clinicians. If we can provide human decision-makers with a simplified set of interpretable composite indices (i.e., combining information about groups of related measures into single representative values), it will facilitate effective clinical decision-making. In this study, we built a structured deep embedding model aimed at reducing the dimensionality of the input variables by grouping related measurements as determined by domain experts (e.g., clinicians). Our results suggest that composite indices representing liver function may consistently be the most important factor in the early detection of pancreatic cancer (PC). We propose our model as a basis for leveraging deep learning toward developing composite indices from EHR for predicting health outcomes, including but not limited to various cancers, with clinically meaningful interpretations.

Inflammatory Bowel Disease: Focus on Enteropathic Arthritis and Therapy.

Inflammatory bowel disease (IBD) is a chronic inflammatory disease primarily affecting the gastrointestinal (GI) tract and other organs. In this article, we provide a comprehensive review of IBD, particularly in the context of enteropathic arthritis and its therapeutic advances. Patients with IBD present with intestinal and extraintestinal manifestations (EIMs). Enteropathic arthritis or arthritis associated with IBD (Crohn's disease [CD] and ulcerative colitis [UC]) is the most common EIM and can involve both peripheral and axial joints with some overlaps. Furthermore, peripheral arthritis can be divided into two subcategories. Due to its varied inflammatory presentations and association with NOD2 mutations, CD can mimic other autoimmune and autoinflammatory diseases. Differential diagnosis should be extended to include another NOD2-associated disease, Yao syndrome. Therapy for IBD entails a myriad of medications and procedures, including various biologics targeting different pathways and Janus kinase (JAK) inhibitors. A better understanding of the therapeutic efficacy and mechanism of each drug aids in proper selection of more effective treatment for IBD and its associated inflammatory arthritis.

Post-operative prevention and monitoring of Crohn's disease recurrence.

Crohn's disease (CD) and ulcerative colitis (UC) are relapsing and remitting chronic inflammatory diseases of the gastrointestinal tract. Although surgery for UC can provide a cure, surgery for CD is rarely curative. In the past few decades, research has identified risk factors for postsurgical CD recurrence, enabling patient risk stratification to guide monitoring and prophylactic treatment to prevent CD recurrence. A MEDLINE literature review identified articles regarding post-operative monitoring of CD recurrence after resection surgery. In this review, we discuss the evidence on risk factors for post-operative CD recurrence as well as suggestions on post-operative management.

Perioperative Management of Ulcerative Colitis: A Systematic Review.

BACKGROUND: Patients with ulcerative colitis may require colectomy for severe disease unresponsive or refractory to pharmacological therapy. Managing ulcerative colitis is complicated because there are many factors at play, including patient optimization and treatment, as the guidance varies on the ideal perioperative use of corticosteroids, immunomodulators, biologics, and small molecule agents. OBJECTIVE: A systematic literature review was performed to describe the current status of perioperative management of ulcerative colitis. DATA SOURCES: PubMed and Cochrane databases were used. STUDY SELECTION: Studies published between January 2000 and January 2022, in any language, were included. Articles regarding pediatric or endoscopic management were excluded. INTERVENTIONS: Perioperative management of ulcerative colitis was included. MAIN OUTCOME MEASURES: Successful management, including reducing surgical complication rates, was measured. RESULTS: A total of 121 studies were included in this review, including 23 meta-analyses or systematic reviews, 25 reviews, and 51 cohort studies. LIMITATIONS: Qualitative review including all study types. The varied nature of study types precludes quantitative comparison. CONCLUSION: Indications for colectomy in ulcerative colitis include severe disease unresponsive to medical treatment and colitis-associated neoplasia. Urgent colectomy has a higher mortality rate than elective colectomy. Corticosteroids are associated with postsurgical infectious complications and should be stopped or weaned before surgery. Biologics are not associated with adverse postoperative effects and do not necessarily need to be stopped preoperatively. Additionally, the clinician must assess individuals' comorbidities, nutrition status, and risk of venous thromboembolism. Nutritional imbalance should be corrected, ideally at the preoperative period. Postoperatively, corticosteroids can be tapered on the basis of the length of preoperative corticosteroid use.

Endoscopic Therapy for Pouch Leaks and Strictures: A Systematic Review.

BACKGROUND: Patients with ulcerative colitis refractory to medication or familial adenomatous polyposis may require ileal pouch-anal anastomosis after a colectomy. IPAA is generally well tolerated. However, patients can experience posttreatment complications, including pouch strictures and leaks. Medical therapy has a limited role in mechanical fibrotic strictures, whereas surgery is invasive and costly. In the past few decades, endoscopic therapies have provided a less invasive and less costly intervention for pouch strictures and leaks. OBJECTIVE: This systematic literature review aimed to describe the status of advancements in endoscopic therapy for pouch leaks and strictures. DATA SOURCES: The sources used were PubMed and Cochrane databases. STUDY SELECTION: Studies between January 1990 and January 2022, in any language, were included. Articles regarding surgical management or pouches other than adult ileal pouch-anal anastomosis were excluded. INTERVENTIONS: Endoscopic management of acute and chronic leaks and strictures ileal pouch-anal anastomosis was included. MAIN OUTCOME MEASURES: Successful management (including persistent leak or stricture, pouch failure, subsequent endoscopy, or surgery) was measured. RESULTS: Sixty-one studies were included in this review, including 4 meta-analyses or systematic reviews, 11 reviews, 17 cohort studies, and 18 case series. LIMITATIONS: The limitations include qualitative review of all study types, with no randomized controlled studies available. CONCLUSION: Ileal pouch-anal anastomosis leaks are various in configuration, and endoscopic therapies have included clipping leaks at the tip of the "J" as well as endoscopic sinusotomy. Endoscopic therapies for pouch strictures have included endoscopic balloon dilation, endoscopic stricturotomy, and endoscopic stricturoplasty, which are now considered first-line therapies for pouch strictures. Endoscopic balloon dilation has shown safety and efficacy in single, short, and straight strictures and endoscopic stricturotomy for refractory long, fibrotic, anastomotic strictures. Endoscopic therapies can delay or prevent invasive surgeries. Key tenets of successful endoscopic therapy include patient and lesion candidacy, an experienced endoscopist, and adequate rescue surgery plans.

Increasing rates of venous thromboembolism among hospitalised patients with inflammatory bowel disease: a nationwide analysis.

BACKGROUND: Venous thromboembolism (VTE) is a significant cause of morbidity and mortality among patients with inflammatory bowel disease (IBD). However, data on national trends remain limited. AIMS: To assess national trends in VTE-associated hospitalisations among patients with IBD as well as risk factors for, and mortality associated with, these events METHODS: Using the U.S. Nationwide Inpatient Sample from 2000-2018, temporal trends in VTE were assessed using the National Cancer Institute's Joinpoint Regression Program with estimates presented as the average annual percent change (AAPC) with 95% confidence intervals (CIs). RESULTS: Between 2000 and 2018, there were 4,859,728 hospitalisations among patients with IBD, with 128,236 (2.6%) having a VTE, and 6352 associated deaths. The rate of VTE among hospitalised patients with IBD increased from 192 to 295 cases per 10,000 hospitalisations (AAPC 2.4%, 95%CI 1.4%, 3.4%, p < 0.001), and remained significant when stratified by ulcerative colitis (UC) and Crohn's disease as well as by deep vein thrombosis and pulmonary embolism. On multivariable analysis, increasing age, male sex, UC (aOR: 1.30, 95%CI 1.26, 1.33), identifying as non-Hispanic Black, and chronic corticosteroid use (aOR: 1.22, 95%CI 1.16, 1.29) were associated with an increased risk of a VTE-associated hospitalisation. CONCLUSION: Rates of VTE-associated hospitalisations are increasing among patients with IBD. Continued efforts need to be placed on education and risk reduction.

Water and Meadow Views Both Afford Perceived but Not Performance-Based Attention Restoration: Results From Two Experimental Studies.

Attention Restoration Theory proposes that exposure to natural environments helps to restore attention. For sustained attention-the ongoing application of focus to a task, the effect appears to be modest, and the underlying mechanisms of attention restoration remain unclear. Exposure to nature may improve attention performance through many means: modulation of alertness and one's connection to nature were investigated here, in two separate studies. In both studies, participants performed the Sustained Attention to Response Task (SART) before and immediately after viewing a meadow, ocean, or urban image for 40 s, and then completed the Perceived Restorativeness Scale. In Study 1 (n = 68), an eye-tracker recorded the participants' tonic pupil diameter during the SARTs, providing a measure of alertness. In Study 2 (n = 186), the effects of connectedness to nature on SART performance and perceived restoration were studied. In both studies, the image viewed was not associated with participants' sustained attention performance; both nature images were perceived as equally restorative, and more restorative than the urban image. The image viewed was not associated with changes in alertness. Connectedness to nature was not associated with sustained attention performance, but it did moderate the relation between viewing the natural images and perceived restorativeness; participants reporting a higher connection to nature also reported feeling more restored after viewing the nature, but not the urban, images. Dissociation was found between the physiological and behavioral measures and the perceived restorativeness of the images. The results suggest that restoration associated with nature exposure is not associated with modulation of alertness but is associated with connectedness with nature.

Deep learning on time series laboratory test results from electronic health records for early detection of pancreatic cancer.

The multi-modal and unstructured nature of observational data in Electronic Health Records (EHR) is currently a significant obstacle for the application of machine learning towards risk stratification. In this study, we develop a deep learning framework for incorporating longitudinal clinical data from EHR to infer risk for pancreatic cancer (PC). This framework includes a novel training protocol, which enforces an emphasis on early detection by applying an independent Poisson-random mask on proximal-time measurements for each variable. Data fusion for irregular multivariate time-series features is enabled by a "grouped" neural network (GrpNN) architecture, which uses representation learning to generate a dimensionally reduced vector for each measurement set before making a final prediction. These models were evaluated using EHR data from Columbia University Irving Medical Center-New York Presbyterian Hospital. Our framework demonstrated better performance on early detection (AUROC 0.671, CI 95% 0.667 - 0.675, p < 0.001) at 12 months prior to diagnosis compared to a logistic regression, xgboost, and a feedforward neural network baseline. We demonstrate that our masking strategy results greater improvements at distal times prior to diagnosis, and that our GrpNN model improves generalizability by reducing overfitting relative to the feedforward baseline. The results were consistent across reported race. Our proposed algorithm is potentially generalizable to other diseases including but not limited to cancer where early detection can improve survival.

Endoscopic Balloon Dilation Is Cost-Effective for Crohn's Disease Strictures.

BACKGROUND: Endoscopic balloon dilation (EBD) has emerged as an alternative intervention to manage Crohn's disease (CD) strictures. We determined the cost-effectiveness of EBD versus resection surgery for patients with short (< 4-5 cm) primary or secondary/anastomotic small or large bowel strictures. METHODS: A microsimulation state-transition model analyzed the benefits and risks of EBD and resection surgery for patients with primary or anastomotic CD strictures. Our primary outcome was quality-adjusted life years (QALYs) over ten years, and strategies were compared using a willingness to pay of $100,000/QALY from a societal perspective. Costs (2021 $US) and incremental cost-effectiveness ratios (ICER) were calculated. Deterministic 1-way and probabilistic analyses assessed model uncertainty. RESULTS: The EBD strategy cost $19,822 and resulted in 6.18 QALYs while the surgery strategy cost $41,358 and resulted in 6.37 QALYs. Surgery had an ICER of $113,332 per QALY, making EBD a cost-effective strategy. The median number of EBDs was 5 in the EBD strategy and 0 in the surgery strategy. The median number of surgeries was 2 in the surgery strategy and 1 in the EBD strategy. Of individuals who initially received EBD, 50.4% underwent subsequent surgery. One-way sensitivity analyses showed that the probabilities of requiring repeated interventions, surgery mortality (< 0.7%), and quality of life after interventions were the most influential model parameters. Probabilistic sensitivity analyses favored EBD in 50.9% of iterations. CONCLUSIONS: EBD is a cost-effective strategy for managing CD strictures. Differences in patient risk and quality of life after intervention impact cost-effectiveness. Intervention decisions should consider cost-effectiveness, patient risks, and quality of life.

Risk of corticosteroid treatment and hospitalization after checkpoint inhibitor and radiation therapy in patients with cancer.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are potent new cancer therapies but can cause serious immune-related adverse events. ICIs have contributed significantly to improved survival and thereby provide more opportunity for the development of local disease symptomatology requiring palliative radiation. Radiation therapy (RT) has also recently shown benefit in the oligometastatic setting. Data on the interaction and safety of concurrent ICIs and RT are limited. METHODS: In this retrospective cohort study using a large medical claims database from 2010 to 2017, the need for corticosteroid therapy and the risk of hospitalization within 180 days of treatment with an ICI were determined for patients with a diagnosis of malignant melanoma or lung cancer. Patients were stratified by the use of RT within the 30 days before and after ICI therapy. RESULTS: In all, 2020 patients (218 with RT and 1802 without RT) met the inclusion criteria for prednisone analysis, whereas 3519 patients (361 with RT and 3158 without RT) met the inclusion criteria for all other analyses. In a univariable analysis, RT was not associated with the need for prednisone (relative risk [RR], 1.2; 95% confidence interval [CI], 0.8-1.9) or methylprednisolone (RR, 1.1; 95% CI, 0.7-2.0). When the end point was hospitalization, RT was significantly associated with hospitalization after ICI therapy for certain cancer/drug combinations (RR for lung cancer/programmed death 1 receptor inhibitors, 1.4; 95% CI, 1.2-1.6; P < .001; RR for melanoma/ipilimumab, 2.0; 95% CI, 1.0-3.5; P = .03). CONCLUSIONS: In patients treated with ICIs, receiving RT was not associated with a higher risk of requiring corticosteroid therapy in comparison with not receiving RT. However, RT was associated with a higher risk of hospitalization, although this finding may be a result of differences in the underlying patient illness severity or oncologic disease burden at the baseline. LAY SUMMARY: Data on the interaction of immunotherapy (immune checkpoint inhibitors) and radiation therapy and the safety of combining them are limited. Using a large database, this study has found that patients treated concurrently with immune checkpoint inhibitors and radiation therapy are not at increased risk for requiring corticosteroid therapy (which is used as a proxy for immune-related adverse events). However, concurrent therapy is associated with a higher risk of hospitalization, although this finding may be due to differences in the underlying patient illness severity (sicker patients may require both immunotherapy and radiation therapy).

Risk of Postpartum Flare Hospitalizations in Patients with Inflammatory Bowel Disease Persists After Six Months.

BACKGROUND: Although patients with IBD are at higher risk for flares during the postpartum period, little is known about the risk factors, timeline, and healthcare-associated costs of a readmission flare. AIMS: To ascertain the timeline in which patients are hospitalized for postpartum inflammatory bowel disease (IBD) flares, and the associated risk factors. METHODS: This is a nationwide retrospective cohort study of 7054 patients with IBD who delivered between 2010-2014 obtained from the National Readmissions Database. The presence of IBD was defined using previously validated International Classification of Diseases codes, and univariable and multivariable regression models were performed to assess risk factors associated with a postpartum flare hospitalization over the nine-month observation period. RESULTS: A total of 353 (5.0%) patients were hospitalized for a postpartum IBD flare, with approximately one-third (30.0%) readmitted after 6 months. On multivariable analysis, having Crohn's disease (aRR 1.47, 95%CI 1.16-1.88), Medicare insurance (aRR 3.30, 95%CI 2.16-5.02), and ≥ 2 comorbidities (aRR 1.34, 95%CI 1.03-1.74) were independently associated with a higher risk of an IBD flare hospitalization. Compared to patients aged 25-29, those 20-24 were at higher risk for an IBD flare readmission (aRR 1.58, 95%CI 1.17-2.13), whereas patients aged 35-39 years were at lower risk (aRR 0.63, 95%CI 0.43-0.92). CONCLUSIONS: Among patients with IBD, Crohn's disease, Medicare insurance, multiple comorbidities, and younger age were independent risk factors for a postpartum IBD flare hospitalization. As approximately one-third of these readmissions occurred after 6 months, it is imperative to ensure adequate follow-up and treatment for postpartum IBD patients, particularly in the extended postpartum period.

Delivery risks and outcomes associated with grand multiparity.

BACKGROUND: There is limited recent US national data on risk for adverse outcomes associated with grand multiparity. OBJECTIVE: To examine the association between grand multiparity and severe maternal morbidity (SMM) and other adverse outcomes during delivery hospitalizations in the United States. METHODS: This repeat cross-sectional study evaluated delivery hospitalizations from 2000 through the third quarter of 2015 to women aged 15-54 in the National (Nationwide) Inpatient Sample database. Temporal trends in deliveries to women with grand multiparity were analyzed using the Cochran-Armitage trend test. The primary outcome studied was SMM, a composite of adverse outcomes defined by the Centers for Disease Control and Prevention. The exposure of interest was grand multiparity diagnosis during delivery hospitalization. Other adverse outcomes analyzed included placental abruption, preterm delivery, postpartum hemorrhage, disseminated intravascular coagulation, shock, hysterectomy, pulmonary edema and acute heart failure, transfusion of blood or blood products, hypertensive diseases of pregnancy, cesarean delivery, eclampsia, and acute renal failure. Log linear regression models were performed to determine the relationship between grand multiparity and adverse outcomes with measures of association demonstrated as unadjusted (RR) and adjusted risk ratios (aRR) with 95%CIs. RESULTS: From 2000 to 2015, there were an estimated 62,672,862 hospital deliveries with 386,019 deliveries in the setting of grand multiparity. The number of deliveries with a grand multiparity diagnosis increased over the study period from 4.2 per 1000 deliveries in 2000 to 8.6 per 1000 in 2015 (p < .01). Women with grand multiparity were more likely to be older, have comorbidities, be Hispanic or non-Hispanic Black, be from a lower ZIP code income quartile, have Medicaid insurance, and present to an urban teaching hospital for delivery (p < .01 for all). On univariable analysis, grand multiparity was associated with SMM (RR 1.27, 95%CI 1.23-1.32). However, in adjusted analyses accounting for hospital, clinical, and demographic factors, women with grand multiparity were at lower risk of SMM (aRR 0.93, 95%CI 0.89, 0.96). On analysis of individual adverse outcomes, grand multiparity was associated with a higher risk of placental abruption (RR 1.28, 95%CI 1.24-1.31), preterm delivery (RR 1.17, 95%CI 1.16-1.18), postpartum hemorrhage (RR 1.30, 95%CI 1.28-1.32), disseminated intravascular coagulation (RR 1.23, 95%CI 1.16-1.31), shock (RR 2.50, 95%CI 2.20-2.85), hysterectomy (RR 3.20, 95%CI 3.30, 3.41), pulmonary edema and acute heart failure (RR 1.33, 95%CI 1.24-1.42), and transfusion of blood or blood products (RR 1.74, 95%CI 1.70-1.79). Conversely, grand multiparity was associated with a lower risk of hypertensive diseases of pregnancy (RR 0.85, 95%CI 0.84-0.86), cesarean delivery (RR 0.96, 95%CI 0.95-0.96), and eclampsia (RR 0.69, 95%CI 0.60-0.79). There was no significant association between grand multiparity and acute renal failure. CONCLUSIONS: Delivery hospitalizations with a grand multiparity diagnosis were not associated with increased risk for SMM in adjusted analysis. Grand multiparity was associated with increased risk for hysterectomy and shock although absolute increased risk for these complications was small.

Cost-effectiveness of Venous Thromboembolism Prophylaxis After Hospitalization in Patients With Inflammatory Bowel Disease.

BACKGROUND: Patients with inflammatory bowel disease (IBD) have a 2- to 3-fold greater risk of venous thromboembolism (VTE) than patients without IBD, with increased risk during hospitalization that persists postdischarge. We determined the cost-effectiveness of postdischarge VTE prophylaxis among hospitalized patients with IBD. METHODS: A decision tree compared inpatient prophylaxis alone vs 4 weeks of postdischarge VTE prophylaxis with 10 mg/day of rivaroxaban. Our primary outcome was quality-adjusted life years (QALYs) over 1 year, and strategies were compared using a willingness to pay of $100,000/QALY from a societal perspective. Costs (in 2020 $USD), incremental cost-effectiveness ratios (ICERs) and number needed to treat (NNT) to prevent 1 VTE and VTE death were calculated. Deterministic 1-way and probabilistic analyses assessed model uncertainty. RESULTS: Prophylaxis with rivaroxaban resulted in 1.68-higher QALYs per 1000 persons compared with no postdischarge prophylaxis at an incremental cost of $185,778 per QALY. The NNT to prevent a single VTE was 78, whereas the NNT to prevent a single VTE-related death was 3190. One-way sensitivity analyses showed that higher VTE risk >4.5% and decreased cost of rivaroxaban ≤$280 can reduce the ICER to <$100,000/QALY. Probabilistic sensitivity analyses favored prophylaxis in 28.9% of iterations. CONCLUSIONS: Four weeks of postdischarge VTE prophylaxis results in higher QALYs compared with inpatient prophylaxis alone and prevents 1 postdischarge VTE among 78 patients with IBD. Although postdischarge VTE prophylaxis for all patients with IBD is not cost-effective, it should be considered in a case-by-case scenario, considering VTE risk profile, costs, and patient preference.