Interaction between inflammatory bowel disease, physical activity, and myokines: Assessment of serum irisin levels.

Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, showed a wide spectrum of intestinal and extra-intestinal manifestations, which rendered the patients physically inactive and impaired their quality of life. It has been found that physical activity is a non-pharmacological intervention that improves the quality of life for those patients. Irisin is one member of the myokines secreted by muscle contraction during exercise and could be used as an anti-inflammatory biomarker in assessing the physical activity of IBD patients. In addition, experimental studies showed that exogenous irisin significantly decreased the inflammatory markers and the histological changes of the intestinal mucosa observed in experimental colitis. Furthermore, irisin produces changes in the diversity of the microbiota. Therefore, endogenous or exogenous irisin, via its anti-inflammatory effects, will improve the health of IBD patients and will limit the barriers to physical activity in patients with IBD.

Impact of sex and socioeconomic status on the likelihood of surgery, hospitalization, and use of medications in inflammatory bowel disease: a systematic review and meta-analysis.

BACKGROUND: Inflammatory bowel diseases (IBDs) are associated with high healthcare utilization. This systematic review aimed to summarize what is known about the impact of sex, income, and education on the likelihood of bowel surgery, hospitalization, and use of corticosteroids and biologics among patients with IBD. METHODS: We used EMBASE, MEDLINE, CINAHL, and Web of Science to perform a systematic literature search. Pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random effects meta-analysis for the impact of sex on the likelihood of surgery and hospitalization. In addition, we performed subgroup analyses of the effect of IBD type (Crohn's disease or ulcerative colitis) and age. Finally, meta-regression was undertaken for the year of publication. RESULTS: In total, 67 studies were included, of which 23 studies were eligible for meta-analysis. In the main meta-analysis, male sex was associated with an increased likelihood of bowel surgery (HR 1.42 (95% CI 1.13;1.78), which was consistent with the subgroup analysis for UC only (HR 1.78, 95% CI 1.16; 2.72). Sex did not impact the likelihood of hospitalization (OR 1.05 (95% CI 0.86;1.30), although the subgroup analysis revealed an increased likelihood of hospitalization in CD patients (OR 1.42, 95% CI 1.28;1.58). In 9 of 10 studies, no significant sex-based differences in the use of biologics were reported, although in 6 of 6 studies, female patients had lower adherence to biologics. In 11 of 13 studies, no significant sex-based difference in the use of corticosteroids was reported. The evidence of the impact of income and education on healthcare utilization was sparse and pointed in different directions. The substantial heterogeneity between studies was explained, in part, by differences in IBD type and age. CONCLUSIONS: The results of this systematic review indicate that male patients with IBD are significantly more likely to have surgery than female patients with IBD but are not, overall, more likely to be hospitalized, whereas female patients appear to have statistically significantly lower adherence to biologics compared to male patients. Thus, clinicians should not underestimate the impact of sex on healthcare utilization. Evidence for income- and education-based differences remains sparse. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022315788.

Inflammatory bowel disease training assessment of gastroenterology fellows in Saudi Arabia.

BACKGROUND: Recent advancement and complexity in the management of inflammatory bowel disease (IBD) has made it challenging for gastroenterology (GI) fellows to obtain competency and confidence in managing the complex IBD patient. We aimed to evaluate the confidence and training in IBD among GI fellows in Saudi Arabia. METHODS: We conducted an electronic, voluntary, and anonymous multicenter survey study of GI fellows in Saudi Arabia, from 1/5/2023 to 1/9/2023. The survey evaluated the fellows' confidence level in IBD management, methods of training received, and the amount of additional training desired in 20 core IBD domains. GI fellows' preferred learning method was also evaluated. RESULTS: A total of 65 GI fellows responded to the survey. In the entire cohort, >50% of fellows reported low confidence in 7 out of 20 IBD management domains, which included 71% in managing j-pouch disorders, 67% in managing the elderly/frail patient with IBD, 60% in managing extraintestinal manifestations, 57% in recommending preventative health services, and 54% in counseling patients on small molecules. Receiving >4 IBD didactic sessions per year was significantly associated with high confidence in managing j-pouch disorders (44.4% vs 13.3%, P = 0.05) and managing the elderly/frail patient with IBD (86.7% vs 50.0%, P = 0.03). Doing an external rotation to expand IBD knowledge was associated with high confidence in managing the elderly/frail patient with IBD (100% vs 26.7%, P = 0.01). CONCLUSION: Many GI fellows lacked confidence and training in key domains of IBD management. Enhancing IBD exposure with didactics and external rotations improved fellows' confidence in specific domains.

Granzyme B PET Imaging for Assessment of Disease Activity in Inflammatory Bowel Disease.

Developing a noninvasive imaging method to detect immune system activation with a high temporal resolution is key to improving inflammatory bowel disease (IBD) management. In this study, granzyme B (GZMB), typically released from cytotoxic T and natural killer cells, was targeted using PET with 68Ga-NOTA-GZP (where GZP is ß-Ala-Gly-Gly-Ile-Glu-Phe-Asp-CHO) to detect early intestinal inflammation in murine models of colitis. Methods: Bioinformatic analysis was used to assess the potential of GZMB as a biomarker for detecting IBD and predicting response to treatment. Human active and quiescent Crohn disease and ulcerative colitis tissues were stained for GZMB. We used IL-10-/- mice treated with dextran sulfate sodium (DSS) as an IBD model, wild-type C57BL/6J mice as a control, and anti-tumor necrosis factor as therapy. We used a murine GZMB-binding peptide conjugated to a NOTA chelator (NOTA-GZP) labeled with 68Ga as the PET tracer. PET imaging was conducted at 1, 3, and 4 wk after colitis induction to evaluate temporal changes. Results: Bioinformatic analysis showed that GZMB gene expression is significantly upregulated in human ulcerative colitis and Crohn disease compared with the noninflamed bowel by 2.98-fold and 1.92-fold, respectively; its expression is lower by 2.16-fold in treatment responders than in nonresponders. Immunofluorescence staining of human tissues demonstrated a significantly higher GZMB in patients with active than with quiescent IBD (P = 0.032).68Ga-NOTA-GZP PET imaging showed significantly increased bowel uptake in IL-10-/- mice with DSS-induced colitis compared with vehicle-treated IL-10-/- mice (SUVmean, 0.75 vs. 0.24; P < 0.001) and both vehicle- and DSS-treated wild-type mice (SUVmean, 0.26 and 0.37; P < 0.001). In the IL-10-/- DSS-induced colitis model, the bowel PET probe uptake decreased in response to treatment with tumor necrosis factor-α (SUVmean, 0.32; P < 0.001). There was a 4-fold increase in colonic uptake of 68Ga-NOTA-GZP in the colitis model compared with the control 1 wk after colitis induction. The uptake gradually decreased to approximately 2-fold by 4 wk after IBD induction; however, the inflamed bowel uptake remained significantly higher than control at all time points (week 4 SUVmean, 0.23 vs. 0.08; P = 0.001). Conclusion: GZMB is a promising biomarker to detect active IBD and predict response to treatment. This study provides compelling evidence to translate GZMB PET for imaging IBD activity in clinical settings.

Clinical Education: Psychosocial Assessment and Treatment Planning for Patients with Inflammatory Bowel Disease.

Psychosocial factors play an important role in the disease course and illness experience of patients with inflammatory bowel disease (IBD). Consultation with a health psychologist is an important component of care for many IBD patients and provides an opportunity to identify areas of psychosocial concern, recognize coping deficits and strengths, and facilitate treatment recommendations. Psychosocial assessment in IBD requires a nuanced approach that goes beyond general mental health screening and considers the disease-specific concerns that impact patients. In this paper, we outline strategies for an IBD-focused psychological evaluation, including specific guidance for assessing disease-specific concerns of anxiety, depression, post-traumatic stress, sleep, pain, body image disturbance, food-related quality of life, and psychological resilience.

Development of the Nursing Assessment Tool for the Patient With Inflammatory Bowel Disease.

This study aims to develop and validate a nursing assessment tool for patients with inflammatory bowel disease. In this cross-sectional descriptive study using a quantitative approach, nurses were invited to participate. The Delphi technique was used to obtain a consensus among expert nurses. Descriptive analysis was used for each item on the nursing assessment tool. Overall, 345 nurses were identified; 32 were eligible as experts and 13 validated the consultation. Of the 13 expert nurses, most were female (11, 84.62%), their mean age was 46.36 ± 10.59 years, eight (61.54%) graduated from public institutions, and eight (61.54%) had a master's degree. The initial version had 106 items, which was reduced to 95 items. The content of four domains (identification, health-disease profile, psychobiological needs, and physical examination) was validated in two rounds about the content with more than 80% of agreement. Two domains (sociodemographic data and health conditions, and personal cares) were validated in the first round with more than 80% of agreement. All domains were validated for their appearance during the first round with more than 80% of agreement. The Nursing Assessment Tool for Patients with Inflammatory Bowel Disease (IBD) had a considerable level of agreement regarding content and appearance validation in all dimensions.

COMPARATIVE ASSESSMENT OF SURGICAL TREATMENT OF COMPLICATIONS OF ULCERATIVE COLITIS IN CHILDREN.

Ulcerative colitis is an inflammatory disease of the colon, characterized by a chronic relapsing course, affecting only the colon with hemorrhagic-purulent inflammation of the mucous and submucosal layer of the intestinal wall, as well as the frequent development of local and systemic complications. The incidence of ulcerative colitis is increasing every year. Objective - improving the results of surgical treatment of ulcerative colitis in children through the use of laparoscopic and video-assisted technologies in clinical practice. The work carried out the analysis of the case histories of 75 (boys - 34, girls - 41) children with ulcerative colitis who were treated in surgical departments of Baku and Moscow - over a 12-year period - from 2010 to 2022. This study was a retrospective cohort analysis with prospective database completion. The main clinical group (Group 1) of the study included 53 children with ulcerative colitis (UC), who underwent surgical treatment for abdominal complications using minimally invasive laparoscopic techniques developed in the clinic. There were 25 boys (47.2%), girls - 28 (52.8%). The age of the children ranged from 4 to 17 years. It is characteristic that the main group of patients with UC consisted of adolescent children. Comparative Group 2 in our study included 22 children with UC - 9 boys (40.9%), girls 13 (59.1%), in whom surgical treatment of complications was carried out using previously generally accepted "open" surgical techniques - classical emergency and planned operations - colectomy and proctocolectomy - using wide laparotomy approaches. The technique of laparoscopic total proctocolectomy with direct ileoanal anastomosis, developed and adopted in our clinic, is an effective method of treatment for this serious disease, not inferior to "open" operations in any aspect of versatility, convenience, radicality, etc. Laparoscopic operations can be performed and indicated in almost all clinical situations in children with complicated inflammatory bowel diseases, for emergency indications and routinely, as well as during radical surgical treatment for ulcerative colitis. Endosurgical ostomy operations, total proctocolectomy, ileal retraction with the formation of ileoanal anastomosis are an effective and safe method of treatment in these complex groups of patients.

Inflammatory bowel disease-associated colorectal cancer negatively affects surgery outcomes and health care costs.

BACKGROUND: Inflammatory bowel disease may affect the pathogenesis and clinicopathologic course of colorectal cancer. We sought to characterize the impact of inflammatory bowel disease on outcomes after colectomy and/or proctectomy for a malignant indication. METHODS: Patients diagnosed with colorectal cancer as well as a pre-existing comorbid diagnosis of Crohn's disease or ulcerative colitis between 2018 and 2021 were identified from Medicare claims data. The postoperative textbook outcome was defined as the absence of complications, as well as no extended hospital stay, 90-day readmission, or mortality. Postdischarge disposition and expenditures were also examined. RESULTS: Among 191,684 patients with colorectal cancer, 4,770 (2.5%) had a pre-existing diagnosis of inflammatory bowel disease. Patients with inflammatory bowel disease-associated colorectal cancer were less likely to undergo surgical resection (no inflammatory bowel disease: 47.6% vs inflammatory bowel disease: 42.1%; P < .001). Among patients who did undergo colorectal surgery, individuals with inflammatory bowel disease were less likely to achieve a textbook outcome (odds ratio 0.64 [95% confidence interval 0.58-0.70]). In particular, patients with inflammatory bowel disease had higher odds of postoperative complications (odds ratio 1.24 [1.12-1.38]), extended hospital stay (odds ratio 1.41 [1.27-1.58]), and readmission within 90 days (odds ratio 1.56 [1.42-1.72]) (all P < .05). Patients with inflammatory bowel disease-associated colorectal cancer were less likely to be discharged to their home under independent care (odds ratio 0.77 [0.68-0.87]) and had 12.2% higher expenditures, which correlated with whether the patient had a postoperative textbook outcome. CONCLUSION: One in 40 patients with colorectal cancer had concomitant inflammatory bowel disease. Inflammatory bowel disease was associated with a lower probability of achieving ideal postoperative outcomes, higher postdischarge expenditure, as well as worse long-term survival after colorectal cancer resection.

Health Care Utilization and Direct Costs Prior to Subspecialty Care in Children with Chronic Pain Compared with Other Chronic Childhood Diseases: A Cohort Study.

OBJECTIVES: To understand the burden associated with pediatric chronic pain (CP) on the health care system compared with other costly chronic diseases prior to subspecialty care. STUDY DESIGN: In this retrospective cohort study, we assessed all-cause health care utilization and direct health care costs associated with pediatric CP (n = 91) compared with juvenile arthritis (n = 135), inflammatory bowel disease (n = 90), type 1 diabetes (n = 475) or type 2 diabetes (n = 289), anxiety (n = 7193), and controls (n = 273) 2 and 5 years prior to patients entering subspecialty care in Manitoba, Canada. Linked data from physician encounters, emergency department visits, hospitalizations, and prescriptions were extracted from administrative databases. Differences in health care utilization and direct health care costs associated with CP vs the other conditions were tested using negative binomial and zero-inflated negative binomial regression models, respectively. RESULTS: After adjustment for age at diagnosis, sex, location of residence, and socioeconomic status, CP continued to be associated with the highest number of consulted physicians and subspecialists and the highest number of physician billings compared with all other conditions (P < .01, respectively). CP was significantly associated with higher physician costs than juvenile arthritis, inflammatory bowel disease, type 1 diabetes, type 2 diabetes, or controls (P < .01, respectively); anxiety was associated with the highest physician and prescription costs among all cohorts (P < .01, respectively). CONCLUSION: Compared with chronic inflammatory and endocrinologic conditions, pediatric CP and anxiety were associated with substantial burden on the health care system prior to subspecialty care, suggesting a need to assess gaps and resources in the management of CP and mental health conditions in the primary care setting.

Bayesian compositional models for ordinal response.

Ordinal response is commonly found in medicine, biology, and other fields. In many situations, the predictors for this ordinal response are compositional, which means that the sum of predictors for each sample is fixed. Examples of compositional data include the relative abundance of species in microbiome data and the relative frequency of nutrition concentrations. Moreover, the predictors that are strongly correlated tend to have similar influence on the response outcome. Conventional cumulative logistic regression models for ordinal responses ignore the fixed-sum constraint on predictors and their associated interrelationships, and thus are not appropriate for analyzing compositional predictors.To solve this problem, we proposed Bayesian Compositional Models for Ordinal Response to analyze the relationship between compositional data and an ordinal response with a structured regularized horseshoe prior for the compositional coefficients and a soft sum-to-zero restriction on coefficients through the prior distribution. The method was implemented with R package rstan using efficient Hamiltonian Monte Carlo algorithm. We performed simulations to compare the proposed approach and existing methods for ordinal responses. Results revealed that our proposed method outperformed the existing methods in terms of parameter estimation and prediction. We also applied the proposed method to a microbiome study HMP2Data, to find microorganisms linked to ordinal inflammatory bowel disease levels. To make this work reproducible, the code and data used in this paper are available at https://github.com/Li-Zhang28/BCO.

Savings in social expenditures for work incapacity in patients with inflammatory bowel disease depend on access to innovative therapies in Poland.

OBJECTIVES: Inflammatory bowel diseases (IBD) are an increasing burden for societies. We examined Polish Social Insurance Institution (ZUS) work incapacity expenditures for people with IBD compared with the general population. METHODS: Aggregate data were obtained on ZUS expenditures between 2012 and 2021 in Polish zlotys (PLN). Annual work incapacity benefit expenditures were analyzed and IBD benefit expenditures were examined relative to innovative IBD drug utilization in individual provinces. RESULTS: Between 2012 and 2021, annual ZUS expenditures per person increased, while expenditures per IBD patient decreased. Proportionally, absenteeism was the largest ZUS expenditure in the general population, while disability pensions were the largest in the IBD population. ZUS expenditures due to absenteeism in the general population increased by PLN 282 per person; those due to disability pensions decreased by PLN 85. Disability pension spending due to Crohn's disease (CD) and ulcerative colitis (UC) decreased by PLN 371 and PLN 284, respectively, while absenteeism spending per person with CD and UC decreased (PLN 58 and PLN 35, respectively). Nationwide in 2021, 8.5% of people with CD and 1.9% of those with UC received innovative drugs. The percentage of people receiving innovative drugs and ZUS expenditure per person were inversely related in 9/16 provinces for CD and 5/16 for UC. CONCLUSION: Polish state spending on work incapacity benefits increased in the general population but decreased in people with IBD between 2012 and 2021. Use of innovative drugs was associated with reduced spending per person with IBD in some provinces.

Parental perspectives on pediatric inflammatory bowel disease: Unraveling concerns, and study participation willingness.

OBJECTIVES: The impact of disease burden extends beyond pediatric inflammatory bowel disease (IBD) patients to include their parents. Previous studies, predating the biologic era, have highlighted parental concerns about potential side effects associated with IBD medications. However, there is a notable gap in the literature regarding parents' perceptions of clinical studies involving pediatric IBD patients. This study aims to explore the specific concerns troubling parents of children with IBD, identifying factors influencing these concerns, and assesses parental willingness to allow their child's participation in clinical studies. METHODS: Utilizing social media, we disseminated an anonymous questionnaire to parents of pediatric IBD patients. The questionnaire encompassed queries about parental willingness for their child to partake in clinical studies, aspects of the disease deemed bothersome, and the sense of coherence scale (SOC). RESULTS: Responses were obtained from 101 parents, with a mean age of 46.4, of whom 82.2% were female. Concerns about potential future side effects of their child's medications surpassed worries about disease symptoms (80.04% vs. 73.47%). Linear regression analysis revealed that parents with lower SOC scores, limited medical care accessibility, and a higher age of the child at diagnosis, exhibited heightened concerns about the future impact of the disease on their child (p = 0.016, 0.003, and 0.045, respectively). While a majority rejected participation in studies involving new medications (54.5%), there was greater agreement for studies on nutritional therapies (84.2%) and complementary medicine (91.1%). Classification tree analysis indicated that women were more inclined to permit their child's participation in studies focusing on complementary medicine (adjusted p = 0.002). CONCLUSION: Parents of IBD patients express greater apprehension about potential side effects from IBD medications and display reluctance toward their child participating in clinical studies related to medications.

Molecular Engineering of Activatable NIR-II Hemicyanine Reporters for Early Diagnosis and Prognostic Assessment of Inflammatory Bowel Disease.

Molecular imaging in the second near-infrared window (NIR-II) provides high-fidelity visualization of biopathological events in deep tissue. However, most NIR-II probes produce "always-on" output and demonstrate poor signal specificity toward biomarkers. Herein, we report a series of hemicyanine reporters (HBCs) with tunable emission to NIR-II window (715-1188 nm) and structurally amenable to constructing activatable probes. Such manipulation of emission wavelengths relies on rational molecular engineering by integrating benz[c,d]indolium, benzo[b]xanthonium, and thiophene moieties to a conventional hemicyanine skeleton. In particular, HBC4 and HBC5 possess bright and record long emission over 1050 nm, enabling improved tissue penetration depth and superior signal to background ratio for intestinal tract mapping than NIR-I fluorophore HC1. An activatable inflammatory reporter (AIR-PE) is further constructed for pH-triggered site-specific release in colon. Due to minimized background interference, oral gavage of AIR-PE allows clear delineation of irritated intestines and assessment of therapeutic responses in a mouse model of inflammatory bowel disease (IBD) through real-time NIRF-II imaging. Benefiting from its high fecal clearance efficiency (>90%), AIR-PE can also detect IBD and evaluate the effectiveness of colitis treatments via in vitro optical fecalysis, which outperforms typical clinical assays including fecal occult blood testing and histological examination. This study thus presents NIR-II molecular scaffolds that are not only applicable to developing versatile activatable probes for early diagnosis and prognostic monitoring of deeply seated diseases but also hold promise for future clinical translations.

The clinical and economic burden of illness in the first two years after ostomy creation: a nationwide Danish cohort study.

BACKGROUND: Living with an ostomy is often associated with costly complications. This study examined the burden of illness the first two years after ostomy creation. METHODS: Data from Danish national registries included all adult Danes with an ostomy created between 2002 and 2014. RESULTS: Four cohorts consisted, respectively, of 11,385 subjects with a colostomy and 4,574 with an ileostomy, of which 1,663 subjects had inflammatory bowel disease (IBD) and 1,270 colorectal cancer as cause of their ileostomy. The healthcare cost was significantly higher for cases versus matched controls for all cohorts. In the first year, the total healthcare cost per person-year was €27,962 versus €4,200 for subjects with colostomy, €29,392 versus €3,308 for subjects with ileostomy, €15,947 versus €2,216 when IBD was the underlying cause, and €32,438 versus €4,196 when it was colorectal cancer. Healthcare costs decreased in the second year but remained significantly higher than controls. Hospitalization and outpatient services were primary cost drivers, with ostomy-related complications comprising 8-16% of hospitalization expenses. CONCLUSION: Compared to controls, subjects with an ostomy bear a significant health and financial burden attributable to ostomy-related complications, in addition to the underlying disease, emphasizing the importance of better ostomy care to enhance well-being and reduce economic strain.