Effects of Vedolizumab Therapy on Extraintestinal Manifestations in Inflammatory Bowel Disease

Background

Approximately 15–20% of ulcerative colitis patients and 20–40% of those with Crohn’s disease experience extraintestinal manifestations (EIMs) of their inflammatory bowel disease (IBD). Clinicians who treat IBD must manage EIMs affecting multiple organs that variably correlate with intestinal disease activity. Vedolizumab is a monoclonal antibody for the treatment of IBD with a gut-selective mechanism of action.

Aims

This report evaluates whether vedolizumab is an effective treatment of EIMs, given its gut-specific mechanism of action.

Methods

We report 8 case studies of patients with various EIMs, including pyoderma gangrenosum, peripheral arthralgia/arthritis, axial arthropathies, erythema nodosum, and uveitis, who received vedolizumab therapy.

Results

Vedolizumab therapy was effective for pyoderma gangrenosum in ulcerative colitis, uveitis, erythema nodosum, polyarticular arthropathy, and ankylosing spondylitis/sacroiliitis but did not provide sustained benefit for the treatment of pyoderma gangrenosum in a patient with Crohn’s disease.

Conclusions

These cases demonstrate the potential of vedolizumab as a treatment of EIMs in patients with IBD.

     

New perspectives on the long-term outcome of segmental colectomy for Crohn’s colitis: an observational study on 200 patients

Background and aims

Surgical management of Crohn’s colitis represents one of the most complex situations in colorectal surgery. Segmental colectomy (SC) and total abdominal colectomy with ileorectal anastomosis (TAC-IRA) are the most common procedures, but there are few available data on their long-term outcome. The aim of the present study was to analyze the long-term outcome of patients who underwent segmental colectomy for Crohn’s colitis, with regard to the risk for total abdominal colectomy.

Methods

In this observational, monocentric, retrospective analysis, we analyzed patients who received a segmental colectomy for Crohn’s colitis at our institution. The database was updated by asking patients to complete a questionnaire by telephone or at the outpatient clinic. Only patients followed up at our Hospital were included. Patients were followed up by a specialized multidisciplinary team (IBD Unit). The primary endpoint was the interval between segmental colectomy and, when performed, total abdominal colectomy.

Results

Between 1973 and 2014, 200 patients underwent segmental colectomy for Crohn’s colitis. The median follow-up was 13.5 years (interquartile range [IQR] 7.8–21.5). Overall, 62 patients (31%) had a surgical recurrence, of these, 42 (21%) received total abdominal colectomy. At multivariate analysis, the presence of ≥?3 sites (HR =?2.47; 95% CI 1.22–5.00; p?=?0.018) and perianal disease (HR =?3.23; 95% CI 1.29–8.07; p?=?0.006) proved to be risk factors for total abdominal colectomy.

Conclusions

The risk for surgical recurrence after SC for Crohn’s colitis is acceptable. We recommend a bowel-sparing policy for the treatment of Crohn’s colitis in any case in which the extent of the disease at the moment of surgery makes the conservative approach achievable.

     

CMV Infection in Pediatric IBD

Purpose of Review

Patients with inflammatory bowel disease (IBD) are predisposed to infections. Cytomegalovirus (CMV) colitis in adult IBD patients, particularly ulcerative colitis (UC), is related to severe or steroid-refractory disease. The aim of this review is to summarize the data on the prevalence and role of CMV colitis in children with IBD.

Recent Findings

Data on CMV colitis in children continue to be very limited due to its rarity. As in adults, children with coexisting UC and CMV tend to have more severe colitis, are resistant to corticosteroids, and are at high risk for colectomies on short- and long-term follow-up.

Summary

In children, as in adults, the significance of CMV colitis, in terms of whether CMV is a pathogen that aggravates acute severe colitis or simply reflects disease severity, is still unknown.

     

Surgical aspects of inflammatory bowel diseases in pediatric and adolescent age groups

Background

Inflammatory bowel disease (IBD) is increasingly encountered in children. Early disease is associated with higher complication rate with increased incidence of surgical intervention.

Patients and methods

From January 2010 to June 2015, 25 patients in the pediatric and adolescent age groups with IBD underwent surgical intervention in our center. They were classified into two groups. Group I included 15 patients with ulcerative colitis where 5 cases had left colon disease underwent left colectomy, while 10 cases had pancolonic disease underwent total colectomy and anal mucosectomy with ileo-anal or ileal pouch-anal anastomosis with covering ileostomy. Group II included 10 cases with Crohn’s disease where the indications for surgery were intestinal obstruction in seven cases, fulminant perianal infection with septic shock in one, perianal fistula and ulcers in one, and growth failure due to resistant intestinal fistula in one.

Results

Group I included eight males and seven females; mean age at surgery was 10.6 years. There were postoperative complications in seven cases in the form of pelvic abscess and wound infection in one, wound infection in two, and recurrent pouchitis in four cases. Group II contained eight males and two females; mean age at surgery was 6.6 years. Two cases had recurrent symptoms after stricturoplasty. The mean length of time from diagnosis to surgery was 2.4 years (ranging from 6 to 36 months).

Conclusion

A multidisciplinary team is mandatory for proper management of IBD cases. The risk of the disease and the expected surgical complications determine the timing of surgical interference.

     

The prevalence,incidence and natural history of primary sclerosing cholangitis in an ethnically diverse population

Background

Primary sclerosing cholangitis (PSC) is a rare chronic cholestatic liver disease often associated with inflammatory bowel diseases (IBD). Current epidemiological data are limited to studies of predominantly Caucasian populations. Our aim was to define the epidemiology of PSC in a large, ethnically diverse US population.

Methods

The Northern California Kaiser Permanente (KP) database includes records from over 3 million people and was searched for cases of PSC between January 2000 and October 2006. All identified charts were reviewed for diagnosis confirmation, IBD co-morbidity, and major natural history endpoints.

Results

We identified 169 (101 males) cases fulfilling PSC diagnostic criteria with a mean age at diagnosis of 44 years (range 11-81). The age-adjusted point prevalence was 4.15 per 100,000 on December 31, 2005. The age-adjusted incidence per 100,000 person-years was not significantly greater in men 0.45 (95% CI 0.33 - 0.61) than women 0.37 (95% CI 0.26 - 0.51). IBD was present in 109/169 (64.5%) cases and was significantly more frequent in men than women with PSC (73.3% and 51.5%, respectively, p = 0.005). The cumulative average yearly mortality rate was 1.9%. Age and serum sodium, creatinine and bilirubin at diagnosis and albumin at last entry were identified as significant factors associated with death, liver transplant or cholangiocarcinoma.

Conclusions

The incidence and prevalence of PSC observed in a representative Northern California population are lower compared to previous studies in Caucasian populations and this might reflect differences in the incidence of PSC among various ethnic groups.

     

Bactericidal/permeability increasing protein gene polymorphism and inflammatory bowel diseases: meta-analysis of five case–control studies

Objective

Bactericidal/permeability increasing protein (BPI) gene polymorphisms have been extensively investigated in terms of their associations with inflammatory bowel disease (IBD), with contradictory results. The aim of this meta-analysis was to evaluate associations between BPI gene polymorphisms and the risk of IBD, Crohn’s disease (CD), and ulcerative colitis (UC).

Methods

Eligible studies from PubMed, Embase, and Cochrane library databases were identified.

Results

Ten studies (five CD and five UC) published in five papers were included in this meta-analysis. G645A polymorphism was associated with a decreased risk of UC in allele model, dominant model, and homozygous model.

Conclusions

Our data suggested that BPI G645A polymorphism was associated with a decreased risk of UC; the BPI G645A polymorphism was not associated with the risk of CD.

     

Cytomegalovirus,inflammatory bowel disease,and anti-TNFα

Background and purpose

Anti-TNFα agents emerged in inflammatory bowel disease (IBD) as an effective option in situations that, otherwise, would be refractory to medical therapy. Cytomegalovirus infection may present with a high spectrum of manifestations and lead to high morbidity and mortality. However, its clinical significance in IBD course remains unknown and data on its association with anti-TNFα are limited.

Aims

This study aims to evaluate cytomegalovirus (CMV) infection/disease in patients with IBD treated with anti-TNFα; if possible, possible risk factors associated with CMV infection/disease in IBD patients under anti-TNFα as well as the influence of CMV infection/disease in IBD course would be determined.

Methods

During three consecutive years, all IBD patients starting infliximab in our department were included. Cytomegalovirus status before anti-TNFα was evaluated. Data regarding IBD, therapeutic and IBD course after infliximab, were recorded. CMV analysis was performed with polymerase chain reaction (PCR)-cytomegalovirus in peripheral blood and colonoscopy with biopsies (histopathology/immunohistochemistry).

Results

We included 29 patients: female—83%; Crohn’s disease–51.8%, ulcerative colitis—44.8%, non-classified colitis—3.4%; 23 cytomegalovirus seropositive. Median follow-up: 19 months (3–36). During follow-up, 14 patients were under combination therapy with azathioprine and 5 did at least 1 cycle of corticosteroids. Twenty-one patients responded to infliximab. We registered 8 exacerbations of IBD. Four patients discontinued infliximab: none had CMV infection. We documented 1 case of intestinal cytomegalovirus infection—detected in biopsies performed per protocol in an asymptomatic UC patient, who responded to valganciclovir without infliximab discontinuation.

Conclusions

Infliximab, with/without immunosuppression, does not confer an increased risk of (re)activation of cytomegalovirus. Cytomegalovirus was not responsible neither for significant morbidity nor mortality in IBD.

     

The Natural History of IBD: Lessons Learned

Purpose of Review

Inflammatory bowel diseases (IBD), which include Crohn’s disease (CD) and ulcerative colitis (UC), are chronic, relapsing diseases with unknown etiologies. The purpose of this review is to present the natural disease course evidenced in the latest epidemiology data.

Recent Findings

The prevalence of IBD is rapidly increasing, affecting five million patients worldwide with the highest incidence observed in Northern Europe and Northern America. It has been shown that both CD and UC patients are at an increased risk for developing cancer of the gastrointestinal tract compared to the general population. Though the disease course of IBD is unpredictable, the rate of surgical treatment has declined potentially as a consequence of the introduction of immunomodulators and new biologic treatment options.

Summary

Treatments with biological agents and/or immunosuppressive drugs as well as disease monitoring with eHealth devices seem to have a positive impact on the disease course. However, long-term follow-up studies are still lacking and therefore no reliable conclusions can be drawn as of yet. Medical compliance is paramount in the treatment of IBD, and continuous research focusing on approaches that increase compliance is also necessary.

     

Alterations in Docosahexaenoic Acid-Related Lipid Cascades in Inflammatory Bowel Disease Model Mice

Background

Inflammatory bowel disease (IBD) is an intestinal disorder, involving chronic and relapsing inflammation of the digestive tract. Dysregulation of the immune system based on genetic, environmental, and other factors seems to be involved in the onset of IBD, but its exact pathogenesis remains unclear. Therefore, radical treatments for ulcerative colitis and Crohn’s disease remain to be found, and IBD is considered to be a refractory disease.

Aims

The aim of this study is to obtain novel insights into IBD via metabolite profiling of interleukin (IL)-10 knockout mice (an IBD animal model that exhibits a dysregulated immune system).

Methods

In this study, the metabolites in the large intestine and plasma of IL-10 knockout mice were analyzed. In our analytical system, two kinds of analysis (gas chromatography/mass spectrometry and liquid chromatography/mass spectrometry) were used to detect a broader range of metabolites, including both hydrophilic and hydrophobic metabolites. In addition, an analysis of lipid mediators in the large intestine and ascites of IL-10 knockout mice was carried out.

Results

The levels of a variety of metabolites, including lipid mediators, were altered in IL-10 knockout mice. For example, high large intestinal and plasma levels of docosahexaenoic acid (DHA) were observed. In addition, arachidonic acid- and DHA-related lipid cascades were upregulated in the ascites of the IL-10 knockout mice.

Conclusions

Our findings based on metabolite profiles including lipid mediators must contribute to development of researches about IBD.

     

Post-Transplant Disease Recurrence in Pediatric PSC

Purpose of Review

Review the current knowledge about recurrent primary sclerosing cholangitis (rPSC) after transplant in children.

Recent Findings

Recurrent PSC is a significant complication that afflicts 16% of children after liver transplantation for primary sclerosing cholangitis (PSC) at a median onset of 38 months post-transplant. Possible risk factors include younger age at PSC diagnosis or transplant, the presence of overlap syndrome or IBD, and post-transplant induction with thymoglobulin. rPSC impairs the patient’s quality of life and can be detrimental to the graft. Preventive options and therapeutic measures are limited. Ursodeoxycholic acid is widely used, but its effect on long-term outcome is unknown. Vancomycin can improve the biochemical profile of rPSC, but it remains unknown whether it halts the disease progression.

Summary

Pediatric liver transplant for primary sclerosis cholangitis can be complicated by recurrence of the disease, which portends poor outcomes. Although few risk factors have been implicated, larger studies with longer follow-ups are needed to characterize cardinal risk factors for rPSC, as well as evaluate possible preventative and therapeutic options.

     

Prevalence and risk factors for low bone mineral density in ulcerative colitis

Background

Inflammatory bowel disease (IBD) has been associated with increased risk of osteopenia and osteoporosis. Several risk factors contribute to this; however, studies evaluating their association have conflicting results.

Methods

We conducted a cross-sectional study with prospective enrollment of adult ulcerative colitis patients attending the Gastroenterology Department of Sawai Man Singh Hospital, Jaipur Rajasthan between June 2015 and December 2015. Demographic data including age, gender, body mass index (BMI), disease duration, type of disease, prior steroid use and vitamin D levels were recorded and compared with bone mineral density (BMD) using dual-energy X-ray absorptiometry (DEXA).

Results

Of the 55 patients enrolled, 41 (74.5%) had abnormal BMD; out of this, 19 (34.5%) had osteopenia and 22 (40.0%) had osteoporosis. In univariate analysis, disease duration and history of steroid use were observed as statistically significant. However, on multivariate analysis, only duration of disease was found to be a significant independent predictor of low BMD. Age, gender, BMI, low levels of vitamin D and steroid usage were not associated with low BMD.

Conclusion

Prevalence of low BMD is common in Indian ulcerative colitis patients. Prolonged disease duration appears to be the major risk factor.

     

Clinical recurrence and re-resection rates after extensive vs. segmental colectomy in Crohn’s colitis: a retrospective cohort study

Background

The aim of the present study was to document long-term clinical recurrence and re-resection rates of segmental and extended colectomy in patients with Crohn’s colitis and to identify risk factors causing recurrence.

Methods

Records of patients with isolated colonic Crohn’s disease who underwent colectomy between 1995 and 2013 and were followed at our medical center were identified. Data on age at diagnosis, gender, smoking, disease location at diagnosis, perianal and rectal disease, indication for surgery, preoperative disease duration, type of operation, primary anastomosis at first operation, length of resected specimen, recurrence of symptoms, postoperative medication, reoperation, and total follow-up time were retrieved.

Results

Thirty-five suitable patients (18 segmental colectomy, 17 extensive colectomy; 17 males; mean age at operation 36.6 years) were identified. Mean age at primary operation was 36 years. The mean preoperative disease duration was 121 months. Postoperative medical treatment was needed in 10 (56 %) patients undergoing segmental colectomy and in 16 (94 %) of those undergoing extensive colectomy (p = 0.01). There was longer reoperation-free survival in the segmental colectomy patient group (p = 0.02) and also a trend toward longer symptom-free survival compared to the extensive colectomy patient group (p = 0.105). There was no correlation between the length of resected bowel and recurrence. Patients operated on at a younger age did not have a higher rate of recurrence of symptoms. Shorter disease duration, smoking, and male gender were risk factors for clinical recurrence.

Conclusions

Segmental resection with primary anastomosis can be safely performed in patients with limited Crohn’s colitis with reasonable clinical recurrence rates.

     

Determinants of Healthcare Utilization Among Veterans with Inflammatory Bowel Disease

Background

Identifying patient-level and disease-specific predictors of healthcare utilization in inflammatory bowel disease (IBD) may allow targeted interventions to reduce costs and improve outcomes.

Aim

To identify demographic and clinical predictors of healthcare utilization among veterans with IBD.

Methods

We conducted a single-center cross-sectional study of veterans with IBD from 1998 to 2010. Demographics and disease characteristics were abstracted by manual chart review. Annual number of IBD-related visits was estimated by dividing total number of IBD-related inpatient and outpatient encounters by duration of IBD care. Associations between predictors of utilization were determined using stepwise multivariable linear regression.

Results

Overall, 676 patients (56% ulcerative colitis (UC), 42% Crohn’s disease (CD), and 2% IBD unclassified (IBDU)) had mean 3.08 IBD-related encounters annually. CD patients had 3.59 encounters compared to 2.73 in UC (p < 0.01). In the multivariable model, Hispanics had less visits compared to Caucasians and African-Americans (2.09 vs. 3.09 vs. 3.42), current smokers had more visits than never smokers (3.54 vs. 2.43, p = 0.05), and first IBD visit at age <40 had more visits than age >65 (3.84 vs. 1.75, p = 0.04). UC pancolitis was associated with more visits than proctitis (3.47 vs. 2.15, p = 0.04). CD penetrating phenotype was associated with more encounters than inflammatory type (4.68 vs. 4.15, p = 0.04).

Conclusions

We found that current tobacco use, age <40 at first IBD visit, UC pancolitis, and CD fistuilizing phenotype in addition to Caucasian and African-American race were independent predictors of increased healthcare utilization. Interventions should be targeted at these groups to decrease healthcare utilization and costs.

     

Postoperative course of laparoscopic subtotal colectomy is affected by prolonged preoperative anti-TNF therapy in patients with acute colitis complicating inflammatory bowel disease

Purpose

The aim of medical treatment of severe acute colitis (SAC) complicating inflammatory bowel disease (IBD) is to avoid surgery, but in 20 to 50% of the cases, colectomy remains necessary. This study aimed to determine the impact of the different lines of medical therapy (i.e., steroids, anti-TNF, or ciclosporin) on postoperative course after laparoscopic subtotal colectomy for SAC complicating IBD.

Methods

All the patients who underwent laparoscopic subtotal colectomy for SAC were included and divided into two groups: those who presented with postoperative morbidity (group A) and those with an uneventful postoperative course (group B). Preoperative physical, endoscopic and radiological data, and medical treatments were compared between groups.

Results

From 2006 to 2015, 65 consecutive patients (32 males, median age = 35 [17–87] years) operated for SAC were included. Postoperative morbidity occurred in 19 patients (29%, group A) and was mainly represented by surgical morbidity (n = 15), including ileus (n = 9), stoma-related complications (n = 5), and intra-abdominal abscess (n = 4). Lichtiger score, endoscopic and radiological evaluations were similar between groups. Patients with morbidity had more frequently presented two previous episodes of SAC (26%) than those without (7%, p = 0.04). Duration of anti-TNF treatment was more frequently longer than 2 months in group A (67%) than that in group B (14%, p = 0.04). No significant differences between groups were noted regarding other preoperative medical treatments and number of lines therapy.

Conclusion

This study suggests that postoperative course after laparoscopic subtotal colectomy for SAC is affected by prolonged preoperative anti-TNF therapy, and in the case of recurrent SAC.

     

College inflammatory bowel disease (C-IBD) day: a targeted approach to shared decision-making in college age students with IBD—a 2-year pilot project

Background

Adherence to treatment is a key therapeutic goal in chronic disorders including diabetes, inflammatory bowel disease (IBD), and hypertension. Non-adherence has been associated with increased health care costs. Previous studies have evaluated adherence to treatment in inflammatory bowel disease, as well as predictors of non-adherence. Higher belief of necessity for medications and membership of IBD patient organizations have been associated with higher medication adherence.

Aim

This study aimed to identify patient reported factors that influence understanding of IBD in college age patients with IBD.

Methods

We conducted questionnaire based survey among a group of college age patients with IBD who attended a structured program. The program consisted of a clinical appointment with an IBD physician, lecture by an IBD physician, followed by interactive segment between patients. Educational material was available for patients to review. In addition, opportunity was given to patients to share their story and ask questions in a safe environment.

Results

A total of 26 patients participated in the two C-IBD sessions over a 2-year period. Twenty-three were enrolled in college, 1 was a recent graduate, and 2 were of college age but not enrolled. All patients thought the program was beneficial, 96% rated the overall experience as “awesome” or “very good.” Seventy-six percent of patients reported sharing their story as the most beneficial. Only 19% found the physician lecture beneficial.

Conclusion

A targeted approach to a vulnerable population with IBD is an additional useful tool in improving understanding of IBD. This may lead to improved compliance with management plans.

     

Aryl Hydrocarbon Receptor Activation Down-Regulates IL-7 and Reduces Inflammation in a Mouse Model of DSS-Induced Colitis

Background and Aims

The pathogenesis of inflammatory bowel disease (IBD) is associated with dysregulation of intestinal immune system. Aryl hydrocarbon receptor (AHR) is believed to control the chronic inflammation in the gut. Besides, interleukin-7 (IL-7) is proved to be an important cytokine that activates mucosal inflammation in IBD. Moreover, intraepithelial lymphocytes (IELs) are one of the key immunological compartments involved in regulating intestinal inflammation. In this study, we investigated the function of 6-formylindolo (3,2-b) carbazole (Ficz), a ligand of AHR, on IL-7, colitis, and IEL phenotypes.

Methods

Colitis was induced by administration of dextran sulfate sodium (DSS) to wild-type C57BL/6J mice for 7 days. Mice were weighted, colon tissues were collected and measured, and histology analyses were performed. IELs were isolated from colon, and the phenotype and activation of IELs were examined using flow cytometry detection. The expression of AHR and IL-7 was measured by immunofluorescence, Western blot, and RT-PCR.

Results

Ficz down-regulated epithelial-derived IL-7 expression in mice with DSS-induced colitis and ameliorated DSS-induced colitis. Ficz also decreased CD8αβ⁺ and CD8⁺ IEL subpopulations, enhanced TCRγδ⁺ IEL subpopulation, and reduced the percentage of activated CD4⁺ and CD8⁺ subpopulations.

Conclusions

Ficz could down-regulate epithelial-derived IL-7 expression in mice with DSS-induced colitis and inhibit inflammation in the gastrointestinal tract of mice. AHR-related compounds might be the new and promising therapeutic medicaments for the treatment of patients with IBD.

     

A national survey on the patterns of treatment of inflammatory bowel disease in Canada

Background

There is a general lack of information on the care of inflammatory bowel disease (IBD) in a broad, geographically diverse, non-clinic population. The purposes of this study were (1) to compare a sample drawn from the membership of a national Crohn's and Colitis Foundation to published clinic-based and population-based IBD samples, (2) to describe current patterns of health care use, and (3) to determine if unexpected variations exist in how and by whom IBD is treated.

Methods

Mailed survey of 4453 members of the Crohn's and Colitis Foundation of Canada. The questionnaire, in members stated language of preference, included items on demographic and disease characteristics, general health behaviors and current and past IBD treatment. Each member received an initial and one reminder mailing.

Results

Questionnaires were returned by 1787, 913, and 128 people with Crohn's disease, ulcerative colitis and indeterminate colitis, respectively. At least one operation had been performed on 1159 Crohn's disease patients, with risk increasing with duration of disease. Regional variation in surgical rates in ulcerative colitis patients was identified. 6-Mercaptopurine/Azathioprine was used by 24% of patients with Crohn's disease and 12% of patients with ulcerative colitis (95% CI for the difference: 8.9% – 15%). In patients with Crohn's disease, use was not associated with gender, income or region of residence but was associated with age and markers of disease activity. Infliximab was used by 112 respondents (4%), the majority of whom had Crohn's disease. Variations in infliximab use based on region of residence and income were not seen. Sixty-eight percent of respondents indicated that they depended most on a gastroenterologist for their IBD care. There was significant regional variation in this. However, satisfaction with primary physician did not depend on physician type (for example, gastroenterologist versus general practitioner).

Conclusion

This study achieved the goal of obtaining a large, geographically diverse sample that is more representative of the general IBD population than a clinic sample would have been. We could find no evidence of significant regional variation in medical treatments due to gender, region of residence or income level. Differences were noted between different age groups, which deserves further attention.

     

Evaluation of interleukin-6 and its soluble receptor components sIL-6R and sgp130 as markers of inflammation in inflammatory bowel diseases

Purpose

Interleukin-6 (IL-6) production and signalling are increased in the inflamed mucosa in inflammatory bowel diseases (IBD). As published serum levels of IL-6 and its soluble receptors sIL-6R and sgp130 in IBD are from small cohorts and partly contradictory, we systematically evaluated IL-6, sIL-6R and sgp130 levels as markers of disease activity in Crohn’s disease (CD) and ulcerative colitis (UC).

Methods

Consecutive adult outpatients with confirmed CD or UC were included, and their disease activity and medication were monitored. Serum from 212 CD patients (815 measurements) and 166 UC patients (514 measurements) was analysed, and 100 age-matched healthy blood donors were used as controls.

Results

IL-6 serum levels were significantly elevated in active versus inactive CD and UC, also compared with healthy controls. However, only a fraction of IBD patients showed increased serum IL-6. IL-6 levels ranged up to 32.7 ng/mL in active CD (>?5000-fold higher than in controls), but also up to 6.9 ng/mL in inactive CD. Increases in active UC (up to 195 pg/mL) and inactive UC (up to 27 pg/mL) were less pronounced. Associations between IL-6 serum levels and C-reactive protein concentrations as well as leukocyte and thrombocyte counts were observed. Median sIL-6R and sgp130 levels were only increased by up to 15%, which was considered of no diagnostic significance.

Conclusions

Only a minority of IBD patients shows elevated IL-6 serum levels. However, in these patients, IL-6 is strongly associated with disease activity. Its soluble receptors sIL-6R and sgp130 do not appear useful as biomarkers in IBD.

     

Predictors of severe outcomes in patients with <Emphasis Type="Italic">Clostridium difficile</Emphasis> infection from a Hispanic population

Background

Factors associated with complicated Clostridium difficile infection (CDI) may vary among populations, and predictors of severe outcomes in CDI have not been studied in Hispanic patients. The aim of this study was to identify factors associated with a higher risk of colectomy, all-cause mortality, and CDI-associated mortality in a Hispanic population.

Methods

We performed a retrospective study of all hospitalized patients with a diagnosis of CDI between January 1, 2011 and September 30, 2015 in a 450-bed teaching hospital in Monterrey, northeast Mexico. Three main outcomes were defined: fulminant colitis with subsequent colectomy, all-cause mortality within 30 days of diagnosis, and CDI-attributable mortality.

Results

Of 261 patients with diarrhea, 176 were diagnosed with CDI. For colectomy, Charlson comorbidity index, ICU stay and mechanical ventilation prior to CDI diagnosis, days with diarrhea prior to treatment, total days of hospital stay and days after CDI diagnosis, elevated ATLAS score, days of diarrhea post CDI treatment, and treatment failure significantly predicted the necessity of surgical treatment with colectomy.

Conclusion

Treatment failure, persistent diarrhea, and a high ATLAS score were identified as risk factors for severe outcomes of CDI. A low albumin concentration and high creatinine were associated with higher overall mortality.

     

Estradiol Has Differential Effects on Acute Colonic Inflammation in the Presence and Absence of Estrogen Receptor β Expression

Background

Inflammatory bowel disease (IBD) increases the risk of developing colon cancer. This risk is higher in men compared to women, implicating a role for female hormones in the protection against this disease. Studies from our laboratory demonstrated that estradiol (E₂) protects against inflammation-associated colon tumor formation when administered following chemical carcinogen and induction of chronic colitis.

Aim

This study seeks to better understand the effect of E₂ on acute colitis in the presence and absence of estrogen receptor β (ERβ).

Methods

Inflammation was induced by 2,4,6-trinitrobenzenesulfonic acid in wild-type (WT) and ERβ knockout (ERβKO) mice implanted with a control or E₂-containing pellet and killed 5 days later. Inflammation and injury were scored by a pathologist. Apoptosis and proliferation were assessed by immunohistochemistry. Cytokines were measured by multiplex analysis.

Results

E₂ treatment reduced inflammation in the middle colon in WT mice and the distal colon in ERβKO mice compared to control mice. WT mice had reduced IL-6, IL-12, IL-17, GM-CSF, IFN-γ, MCP-1, MIP-1α, and TNF-α, and ERβKO had reduced IL-6 and IFN-γ expression in response to E₂. Injury scores were lower in E₂-treated ERβKO mice compared to control ERβKO mice. ERβKO mice had increased proliferation in the basal third of crypts in the distal colon and decreased apoptosis in the proximal colon.

Conclusions

These data suggest that E₂ has differential protective effects against acute colitis in the presence or absence of ERβ and provide insight into how E₂ may protect against IBD.