Disparities in Objective Sleep Quality as Assessed Through Wrist Actigraphy in Minority Patients With Inflammatory Bowel Disease.

BACKGROUND: Inflammatory bowel disease (IBD) is associated with a reduced quality of life. Minority patients with IBD specifically report more impairing symptoms compared with nonminority patients. Sleep quality, a key component of quality of life, is significantly compromised in minority patients compared with nonminority patients. Nevertheless, subjective and objective sleep assessments in minority patients with IBD have not explicitly been assessed. The purpose of this prospective cohort study is to assess and compare objective sleep parameters utilizing wrist actigraphy between minority and nonminority IBD patients. METHODS: In this institutional review board approved study, 74 patients with IBD were recruited and stratified into 2 cohorts by self-identification: white nonminority patients and minority patients. Patients in the minority cohort included black and Hispanic individuals (black and nonblack). Exclusion criteria included significant comorbidity, a history of an underlying sleep disorder, or patients who did not self-identify into categorized cohorts. Sleep was measured not only through wrist-based actigraphy but also with sleep surveys. Sleep parameters were compared between minority and nonminority cohorts. Regression analyses were performed to assess for factors independently associated with parameters of poor sleep quality. RESULTS: Sixty-four patients (86.4%) were included in the final analysis. Thirty-one individuals (48.4%) were categorized into the nonminority cohort, and 33 (51.6%) patients were in the minority cohort. A significantly higher number of minority patients had poorer sleep efficiency and fragmented sleep compared with nonminority patients (90.9% vs 67.7%; P = 0.03 and 87.8% vs 61.3%; P = 0.02). In the adjusted analysis, minority status was independently associated with poor sleep efficiency (odds ratio = 6.41; 95% confidence interval, 1.48-28.17; P = 0.0139) and fragmented sleep (odds ratio = 4.98; 95% confidence interval, 1.09-22.89; P = 0.0389). CONCLUSIONS: Minority patients with IBD were shown to have poorer objective measures of sleep as assessed through wrist actigraphy compared to nonminority patients. Cultural competency in the care of minority patients with IBD, specifically focusing on the management of psychosocial issues, is needed to address these disparities in sleep. The inclusion of minority patients with IBD in studies investigating sleep and other psychosocial issues are warranted not only to assess potential disparities in disease course but also to determine the etiologies of poor sleep in minority patients with IBD.

Safety of Recombinant Zoster Vaccine in Patients with Inflammatory Bowel Disease.

BACKGROUND: Patients with inflammatory bowel disease (IBD) are at increased risk of developing herpes zoster. In October 2017, the FDA approved a two-dose adjuvanted, recombinant herpes zoster vaccine (RZV). There is a theoretical concern that vaccine adjuvants may cause flares in patients with immune-mediated diseases. We aimed to assess the rates of IBD flare and adverse reactions after administration of RZV in a cohort of patients with IBD. METHODS: We conducted a prospective observational study of patients with IBD who received RZV between February 2018 and July 2019 at a tertiary IBD referral center. IBD activity scores were collected from patients during office visit or phone call after vaccination. The primary outcome was rate of IBD flare, defined as an increase in IBD activity, resulting in escalation of medical therapy, following vaccination. The secondary outcomes were rates of local and systemic adverse reactions after vaccination. RESULTS: We identified 67 patients (28 with ulcerative colitis and 39 with Crohn's disease) who received at least one dose of RZV. The two-dose vaccine series was completed by 55 patients (82%). Median duration of follow-up after vaccination was 207 days. One case of IBD flare was identified. No cases of herpes zoster were identified. Local and systemic adverse reactions were reported in 74.6% and 56.7% of patients, respectively. CONCLUSIONS: In this cohort of 67 patients, a low rate of IBD flare (1.5%) was observed after RZV administration. Rates of local and systemic adverse reactions were comparable to those seen in the RZV clinical trials.

Imaging of Gastrointestinal Tract Perforation.

Gastrointestinal tract perforation involving the stomach, duodenum, small intestine, or large bowel occurs as a result of full-thickness gastrointestinal wall injury with release of intraluminal contents into the peritoneal or retroperitoneal cavity. Most cases are associated with high mortality and morbidity, requiring urgent surgical evaluation. Initial patient presentations can be nonspecific with a broad differential, which can delay timely management. This article provides brief overviews of different causes of perforation. Various imaging modalities and protocols are discussed, along with direct and indirect imaging findings of perforation. Specific findings associated with different causes are also described to aid in the diagnosis.

Influenza and Pneumococcal Vaccination Rates in Patients With Inflammatory Bowel Disease.

Patients with inflammatory bowel disease (IBD) are at an increased risk for vaccine-preventable illnesses, such as pneumococcal pneumonia and influenza. We hypothesized that a patient-directed educational program would increase vaccination rates of patients with IBD. We developed a written educational form that was given to all patients over a 15-month period. The form included information about the importance of vaccination and asked patients about their vaccination status. If patients indicated that they were not vaccinated, they were offered a vaccination at the time of their visit. For influenza, the vaccination rates during 3 seasons were compared. For pneumococcal pneumonia, the vaccination rates during a 6-month period before the introduction of the educational program and the rates during the 15-month period after implementation of the intervention were compared. Our form increased the percentage of patients who reported having an influenza vaccination (23% vs 47%; P<.001) and the percentage of patients who reported having a pneumococcal pneumonia vaccination (21% vs 32%; P<.001). We concluded that a simple written educational form designed to assess vaccination status and enable providers to offer same-day influenza and pneumococcal pneumonia vaccinations resulted in a significant increase in influenza and pneumococcal pneumonia vaccination rates among patients in an IBD specialty clinic.

B cells secrete eotaxin-1 in human inflammatory bowel disease.

BACKGROUND: Our previous studies have demonstrated that B cells in human inflammatory bowel disease (IBD) are highly activated and produce copious amounts of chemokines. Here, we showed that B cells produce eotaxin-1, a selective chemokine for acute eosinophilia. Increased levels of activated eosinophils have been found in the intestinal mucosa in patients with IBD, but their role(s) and the regulation of their migration patterns remain poorly defined. METHODS: To determine how B-cell secretion of eotaxin-1 influences eosinophil activation and migration, we performed immunoepidemiological approaches coupled with in vitro studies. B cells and eosinophils from patients with Crohn's disease and ulcerative colitis were isolated, and responses to Toll-like receptor ligands (TLR) were measured and assessed for the relationship with clinical disease. RESULTS: Eotaxin-1 from recirculating B cells, and TLR ligands, regulated eosinophil homing mechanisms in IBD. B cells stimulated with hypo-acylated lipopolysaccharide (LPS) produced copious amounts of eotaxin-1, which influenced eosinophil activation profiles in the bloodstream. We also found that hexa-acylated LPS, such Escherichia coli LPS, directly activated TLR2-expressing and TLR4-expressing eosinophils from patients with IBD to express a different repertoire of mucosal homing receptors, namely CCR9 and CCR10. Whereas B-cell production of eotaxin-1 was correlated with reduced disease activity, eosinophil activation by hexa-acylated LPS was associated with increased disease activity. CONCLUSIONS: These results suggest that systemic TLR ligands influence eosinophil migration patterns, both directly and indirectly, through B cells. Our report uncovers unexpected mechanisms of cross talk between certain immune cells that shed new light on IBD immunology.

Toll-like receptor 2 induces mucosal homing receptor expression and IgA production by human B cells.

There is a need for developing vaccines that elicit mucosal immunity. Although oral or nasal vaccination methods would be ideal, current strategies have yielded mixed success. Toll-like receptor 2 (TLR2) ligands are effective adjuvants and are currently used in the Haemophilus influenzae type B vaccine. Induction of humoral immunity in the mucosa is critical for effective vaccination; thus, we sought to determine the effects of TLR2 ligands on human mucosal B cell differentiation. We demonstrate that TLR2 ligands induce CCR9 and CCR10 expression by circulating B cells and increased chemotaxis to cognate chemokines CCL25 and CCL28 suggesting that TLR2 induces B cell homing to the gastrointestinal tract. TLR2 stimulation of B cells also induced J chain and IgA production demonstrating the induction of mucosal-like antibody secreting cells. These observations suggest that vaccines containing TLR2-ligands as adjuvants could induce mucosal B cell immunity even when delivered in a non-mucosal manner.

Systemic Toll-like receptor ligands modify B-cell responses in human inflammatory bowel disease.

BACKGROUND: Bacteria have a central, although poorly understood, role in inflammatory bowel disease (IBD). Host-bacteria interactions primarily take place in the gastrointestinal tract, but cells may also encounter translocated bacteria in the bloodstream. IBD is associated with activated, circulating Toll-like receptor (TLR)2 and TLR4-expressing B cells suggesting that blood-borne microbial TLR ligands modulate B cell responses. METHODS: Serum levels of lipopolysaccharide (LPS)/endotoxin and high mobility group box 1 (HMGB1), an endogenous TLR ligand, were quantified in Crohn's disease (CD) and ulcerative colitis (UC). Responses of purified B cells to LPS and HMGB1 were correlated with levels of systemic TLR ligands and clinical parameters of disease. RESULTS: While IBD patients have increased levels of blood LPS, the net effect of endotoxemia has unexpected characteristics illustrating that LPS has both pro- and antiinflammatory roles through TLR4+ B cells. Experimental treatment of B cells demonstrates that the antiinflammatory effect of LPS is due to its hypo-acylation of lipid A suggesting an increased prevalence of systemic, hypo-acylated LPS in CD. In contrast, high levels of LPS are associated with disease activity in UC. HMGB1 activates B cells through TLR2 and CD36. Serum levels of HMGB1 correlate with spontaneous IL-8 production by B cells suggesting that blood-borne TLR2 ligands increase B-cell activation in vivo. CONCLUSIONS: Systemic TLR ligands modulate B cells towards either proinflammatory or antiinflammatory activity depending on the predominant ligand(s). Further, the circulating B cell may represent an important proxy for quantifying the LPS lipid A acylation burden in patients with IBD.

Hyperactivated B cells in human inflammatory bowel disease.

IBD is characterized by a chronic, dysregulated immune response to intestinal bacteria. Past work has focused on the role of T cells and myeloid cells in mediating chronic gastrointestinal and systemic inflammation. Here, we show that circulating and tissue B cells from CD patients demonstrate elevated basal levels of activation. CD patient B cells express surface TLR2, spontaneously secrete high levels of IL-8, and contain increased ex vivo levels of phosphorylated signaling proteins. CD clinical activity correlates directly with B cell expression of IL-8 and TLR2, suggesting a positive relationship between these B cell inflammatory mediators and disease pathogenesis. In contrast, B cells from UC patients express TLR2 but generally do not demonstrate spontaneous IL-8 secretion; however, significant IL-8 production is inducible via TLR2 stimulation. Furthermore, UC clinical activity correlates inversely with levels of circulating TLR2+ B cells, which is opposite to the association observed in CD. In conclusion, TLR2+ B cells are associated with clinical measures of disease activity and differentially associated with CD- and UC-specific patterns of inflammatory mediators, suggesting a formerly unappreciated role of B cells in the pathogenesis of IBD.