Category Archives: Uncategorized

Vitamin D Supplementation Did Not Improve Postsurgical Outcomes in Patients with Crohn’s Disease

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Link from Kipp Ellsworth Twitter Feed: Healio Gastro: Vitamin D does not prevent Crohn’s recurrence after resection

Re: Duijvestein M, et al. Abstract 144. Presented at: Digestive Disease Week; May 18-21, 2019; San Diego.

Background: “Researchers conducted a placebo-controlled trial comprising 143 patients with CD to assess the potential anti-inflammatory effects of vitamin D. Patients were randomly assigned to receive either 25,000 International Units of vitamin D3 (n = 72) or placebo (n = 71) weekly for 6 months after their first or second ileocolonic resection.”

Key Finding: “While serum vitamin D levels increased in the vitamin D group and remained unchanged in the placebo group, investigators found no difference in the incidence or severity of endoscopic recurrence at week 26 between the two groups. Cumulative clinical recurrence rates at week 26 were also comparable.”

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Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications/diets (along with potential adverse effects) should be confirmed by prescribing physician/nutritionist.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition

Madrid view from Círculo de Bellas Artes

 

 

IBD Articles -Briefly Noted

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A Dige et al. Gastroenterol 2019; 156: 2208-16. This study evaluated the efficacy of freshly collected autologous adipose tissue injection for healing of perianal fistulas in Crohn’s disease.  The overall healing rate was 57% and the treatment had a good safety profile.

HK Somineni et al. Gastroenterol 2019; 156: 2254-65. The researchers found that DNA methylation patterns (from ~850,000 sites) in blood samples from pediatric patients with Crohn’s disease  (n=164) were associated with inflammation and resolved with treatment of inflammation; thus, the changes in DNA methylation are less likely to be a causative agent in disease development or progression and more likely a biomarker of inflammation.

OB Kelly et al. Inflamm Bowel Dis 2019; 25: 1066-71. Among 316 patients who underwent A/P CT scan for any reason, 49 (16%) had evidence of sacroilitis, indicating this is underdiagnosed in patients with IBD.

BG Feagan et al. Inflamm Bowel Dis 2019; 25: 1028-35. In a post hoc analysis of GEMINI 1 trial (n=769 patients: 149 placebo, 620 vedolizumab), a randomized placebo-controlled trial of vedolizumab for ulcerative coliis, compared to placebo ~40% more patients receiving a full induction of vedolizumab had a sustained clinical remission after 52 weeks of therapy.  Of patients in clinical remission at week 14, 66.5% achieved a sustained clinical remission at week 52 compared with 267% of placebo-treated patients based on partial Mayo score..  Sustained clinical remission was based on partial Mayo score and rectal bleeding subscore..

Best Approach for Identifying Eosinophilic Esophagitis

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A recent study (K Radicic, RF Stokes. Clin Gastroenterol Hepatol 2019; 1408-9) indicated that taking biopsies from three esophageal areas (proximal, mid, and distal)  improved the likelihood of identifying eosinophilic esophagitis (EoE).

Key findings:

  • In their study, among 96 patients with EoE, 55.2% were positive (>15 eos/hpf) in only 1 of the 3 levels.
  • 17 patients (17.7%) were positive in the mid-esophagus alone, and 6 patients (6.3%) were positive in the proximal esophagus alone.

The authors state that a 2-level biopsy protocol missed the diagnosis of EoE in roughly 1 of 5 patients.

My take: This study is provocative. However, the reasons why 3 levels improved their yield could be related to other factors rather than location.

  1. Prior studies have shown higher yield when taking 5 or 6 biopsies rather than fewer biopsies; thus, the location of biopsies may not be as important as the number of specimens
  2. Prior studies have shown that having another pathologist review the slides can increase the yield by ~20%; this indicates that careful review of specimens by itself is helpful.  Perhaps, more specimen containers will increase the time that a pathologist reviews the biopsies.

My view is that if adequate numbers of biopsies are taken from several locations, a single jar for all the specimens should suffice (& reduce costs) –though a formal study could be beneficial to confirm this.

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From NASPGHAN 2014 EoE Slide Set

Is It Worse to Be Sitting at Work or Sitting at Home?

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A recent report indicates that sitting at home is more problematic for health than sitting at work and may be bad news for the manufacturer’s of standing desks.

Time: This Type of Sitting is the Worst for Your Health

Background: For the study, [published in the Journal of the American Heart Association: JM Garcia et al. Full text link Types of Sedentary Behavior and Risk of Cardiovascular Events and Mortality in Blacks: The Jackson Heart Study. https://doi.org/10.1161/JAHA.118.010406] “almost 3,600 African American adults reported the amount of time they’d spent sitting at work, watching television and exercising over the previous year. They also provided demographic, lifestyle and health-history information. The researchers monitored the participants’ health over eight years, during which 129 had a cardiovascular issue and 205 died.”

Key findings:

  • “After adjusting for health and lifestyle factors, the researchers found that “often or always” sitting at work was not associated with a heightened risk of death and heart disease”
  • “But those watching four or more hours of television per day had a 50% higher risk of heart issues and death, compared to those watching two hours or less per day.”
  • From Today: Sitting while watching TV, but not sitting at work, linked with higher health risk: “The health risk of watching lots of TV vanished when people spent 150 minutes or more per week doing moderate-to-vigorous exercise— like brisk walking, running, swimming and cycling.”

Commentary from Time report:

  • “People who spend a good chunk of their free time watching television likely do so at the expense of exercising.”
  • “Vegging in front of the TV may also inspire other unhealthy habits” –like snacking, consuming alcohol, and disrupting sleep patterns.

My take: This study suggests that sitting a lot at work is mainly a problem only for those who sit a lot when they leave work.

Retiro Park, Madrid

 

First Year of Life Antibiotics and Celiac Disease

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Briefly noted:

A recent study (SD Sander et al. Gastroenterol 2019; 156: 2217-29) found an association between antibiotics in the first year of life and celiac disease.

The authors “collected medical information on 1.7 million children, including 3346 with a diagnosis of celiac disease” using nationwide register-based cohorts from Norway and Denmark.

Key finding:

  • “Exposure to systematic antibiotics in the first year of life was positively associated with diagnosed celiac disease,” pooled odds ratio 1.26.  Furthermore, there was a dose-dependent relationship with increasing number of exposures increasing the risk of celiac disease.

My take: The increase in prevalence of celiac disease over that past few decades is likely related to changes in our environment.  These changes affect nearly everyone, but some are more susceptible to immune-related disease that may be triggered by these environmental changes.  This study shows that early exposure to antibiotics is likely to be one of the environmental factors that increase the risk of celiac disease.

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Retiro Park, Glass Palace
Madrid

Vedolizumab More Effective Than Adalimumab for Ulcerative Colitis

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Gastroendonews: Tea Leaves No More: Biologics Head-to-Head Produces a Winner

An excerpt:

In the first head-to-head trial of biologic treatments for inflammatory bowel disease, vedolizumab (Entyvio, Takeda) was nearly 50% more effective than adalimumab (Humira, AbbVie) in inducing clinical and mucosal remission in patients with moderate to severe ulcerative colitis…

They enrolled 771 patients with moderate to severe ulcerative colitis in the VARSITY study and randomly assigned them to receive 52 weeks of treatment with either vedolizumab or adalimumab…

They had failed other conventional therapies, including 25% in each group that had received an anti–tumor necrosis factor (TNF) agent…

  • 31.3% of vedolizumab recipients and 22.5% of those taking adalimumab were in clinical remission after 52 weeks (P=0.0061). Clinical remission was defined as a complete Mayo score of 2 or lower and no subscore greater than 1
  • Nearly 40% of patients who received vedolizumab achieved mucosal healing at 52 weeks, compared with 27.7% of adalimumab recipients (P=0.0005).

My take: This study provides a rationale for vedolizumab to be used as a first-line biologic agent for ulcerative colitis.

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Do Anti-TNF Agents Reduce Surgeries and Hospitalizations?

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Briefly noted:

A recent study (http://dx.doi.org/10.1136/gutjnl-2019-318440; SK Murthy et al. BMJ indicates that anti-TNF therapy has not been effective in significantly lowering CD-related hospitalizations or surgeries.

Full Text Link (from Eric Benchimol twitter feed): Introduction of anti-TNF therapy has not yielded expected declines in hospitalisation and intestinal resection rates in inflammatory bowel diseases: a population-based interrupted time series study)

My take: While big changes in the frequency of these outcomes were not demonstrated in this large study, prior studies, including the RISK study, have shown that anti-TNF therapy can be disease-modifying and reduce the risk of penetrating disease in Crohn’s disease.

Related blog post: CCFA Updates in IBD

 

How Often is Arthritis a Presenting Feature of Pediatric IBD & How to Make the Right Diagnosis

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A recent retrospective study (R Levy et al. J Pediatr 2019; 209: 233-5) analyzed the musculoskeletal presenting manifestations of pediatric inflammatory bowel disease (IBD).

In their cohort of 715 patients with IBD, 137 had arthritis and/or arthralgia.  28 of these 137 patients (3.9% of total cohort) had arthritis preceding the diagnosis of IBD and were eligible for this study.  Only 23 had complete data and were compared with 46 children with arthritis due to JIA (n=21), FMF (n=7), and postinfectious arthritis (n=18).

Key findings:

  • Patients with subsequent IBD diagnosis were more likely to have sacroiliac involvement (34.8% vs. 2.2%), more likely to have anemia (mean hgb 10.5 vs 12), more likely to have low albumin (mean 3.5 vs 4.3) and to have higher inflammatory markers (ESR 81 vs 46; CRP 6.6 vs 4.5 mg/dL)
  • In patients with calprotectin levels, 5 of 6 were >300 mg/kg and one was borderline
  • On direct questioning at time of IBD diagnosis, prolonged gastrointestinal symptoms (e.g. abdominal pain, diarrhea, weight loss, aphthous ulcers) were evident in 78%.
  • 4 of the 23 (17.3%) were diagnosed with IBD during the primary investigation. Ultimately, Crohn’s diagnosis was established in 87% of the IBD group.

My take: This study is important for pediatricians and rheumatologists. ~4% of children presenting with arthritis have IBD.  Careful interrogation for GI symptoms (and perianal exam) will avoid diagnostic delay in most patients as would a stool calprotectin. Features like sacroileitis, and abnormal labs should also increase the suspicion for IBD.

Briefly noted: In a study discussing pediatrician beliefs about JIA (MR Pavo, J de Inocencio, J Pediatr 2019; 209: 236-9) there is an important caveat for GI doctors:

“It is clear that booster vaccinations against measles, mumps, rubella, or varicella zoster virus, can be considered in patients receiving < 15 mg/m-squared/week of MTX [methotrexate]”  (Pediatr Rheumatol Online J 2018; 16: 46).

Related blog post:

  • IBD Update Feb 2019 -last entry shows study indicating that patients with IBD and arthritis were more likely to require biologics.

Calprotectin:

El Retiro Park, Madrid

 

Early Life Events and the Development of Inflammatory Bowel Disease

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Full Text via AGA Journal Link: Events Within the First Year of Life, but Not the Neonatal Period, Affect Risk for Later Development of Inflammatory Bowel Diseases

A recent study (CN Bernstein et al. Gastroenterol 2019; 156: 2190-7; editorial 2124) delves into the topic of early life risk factors for the development of IBD. In the background, the author note that in 2018, 267,983 Canadians (0.73%) were estimated to be living with IBD and there is a forecast that this will increase to 402,853 by 2030.

This study used a Manitoba database and examined the records of individuals diagnosed with between 1984-2010. In addition, they correlated this data with individual data of the postnatal period between 1970-2010. From this database, they analyzed 825 individuals with IBD and 5999 matched controls.

Key Findings:

  • The strongest risk factor for the development of IBD was a maternal diagnosis of IBD with an odds ratio (OR) of 4.53; the OR was higher for CD at 5.98 compared to OR of 2.71 for UC
  • Infections in the first year of life was associated with an OR of 3.06 for IBD diagnosed before age 10 years, and OR of 1.63 for IBD diagnosis before age 20 years.  Only infections in the first year of life were correlated with IBD as infections during the first 3 years of life were not associated with a significant increased risk.
  • While infections in the first year of life were associated with an increase risk of IBD, the authors could not demonstrate that individuals who developed IBD had more infections than unaffected sibling controls (though they did have more infections than the entire control cohort).
  • Highest socioeconomic quintile, also, had an increased OR of 1.35.
  • Gastrointestinal illnesses (like abdominal pain) were not found to be associated with the later development of IBD.

It is unclear whether infections in early life increase the risk of IBD or whether other factors like antibiotics contribute to the higher rate of IBD.  The authors did not find more immunodeficiency disorders in the IBD cohort compared to controls.

My take: This study identified genetic risk as substantially greater than specific environmental risks.  However, the increasing incidence of IBD suggests that environmental factors are quite significant, as genetic risk factors are less likely to change enough to account for the changes in epidemiology.  As such, there are a few explanations:

  1. There are other unidentified environment risk factors
  2. Some individuals are more susceptible to the changes that have occurred in the environment; that is, their environmental exposures are not significantly different from their peers but are significantly different than individuals from 20, 40, 60 and 100 years ago.

From AGA Journal link

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