ANMS Virtual Symposia on Constipation

For those wanting a state-of-the-art review on constipation:

YouTube (1:01) ANMS Virtual Symposia on Constipation

Dr. Jose Garza (one of my partners) gives the first lecture focused on pediatrics -first 18 minutes.

A few points:

  • Miralax is safe (time: 13:45)
  • Senna and bisacodyl are safe and have not been shown to cause dependence (time 14:55)

Study: No Increased Cancer Risk with Ranitidine

Despite theoretical concerns that impurities with N-nitrosodimethylamine (NMDA) identified in samples of ranitidine (trade name: Zantac) could increase the risk of cancer, a recent study (N Mohyuddin et al. DDW 2020; Abstract#152. RISK OF CANCER WITH USE OF RANITIDINE: RESULTS OF A COHORT STUDY OF 65 MILLION US ADULTS) did not find any evidence of this.

Methods: The authors utilized the Explorys database (IBM, New York) which is a source of longitudinal real world deidentified data collected from electronic medical records from over 40 health systems nationwide (65 million) from 1999-2019.

Key findings:

  • 1.62 million users of ranitidine were identified, 3.37 million users of famotidine, and 59.63 million individuals who did not use either H2 blocker.
  • Users of ranitidine and famotidine when compared to the general population, and users of famotidine when compared to ranitidine, were older (p<0.001), smokers (p<0.001), obese (p<0.001), had liver cirrhosis (p<0.001), a history of alcohol use (p<0.001), and a family history of cancer (p<0.001).
  • Ranitidine users had a numerically lower risk for GI cancers (liver, stomach, esophageal, colorectal, and pancreatic cancers) compared to famotidine. Among subjects without risk factors including smoking, obesity, alcohol use, family history, cirrhosis and GERD, the risk of all cancers (excluding non-melanoma skin cancers) was identical for ranitidine and famotidine (OR=1, CI=1.01-1.02, p=0.001).

My take: This large database did NOT identify an increased risk of malignancy with ranitidine over a 20 year span.  Despite this, I don’t expect that the FDA will reverse its recall.

Related blog posts:

Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  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

New Data on Bisacodyl for Pediatric Constipation

A recent retrospective study (S Bonilla et al. JPGN 2020; 71: 288-291. Long-term Use of Bisacodyl in Pediatric Functional Constipation Refractory to Conventional Therapy) provides some reassuring information about the use of bisacodyl for pediatric constipation, n=164.  Bisacodyl’s mechanism of action is due to its ability to cause mucosal secretion and a prokinetic effect on colonic mucosa.

Key findings:

  • Bisacodyl median dose was 5 mg/day, median duration of treatment was 14 months
  • Median number of BM/wk doubled after initiation of bisacodyl from 2 to 4 bm/w (P < 0.001)
  • Approximately 57% of patients had successful response. At long-term follow-up 55% of patients were successfully weaned off bisacodyl (median time of 18 months)
  • Side effects: 8 patients reported abdominal pain, 4 had diarrhea, and 1 had nausea
  • Limitations: open-label study, retrospective study, lack of a placebo-control

My take (from authors): “We observed no long-term complications with its long-term use in children.” Prospective studies are needed.

Related blog posts:

Published IBD-COVID-19 Data from SECURE-IBD & Others

When I received an email in EARLY MARCH of this year regarding SECURE-IBD, I thought the researchers were insightful and proactive.  Recently, the authors published their early findings: EJ Brenner, RC Ungaro et al. Gastroenterol 2020; 159: 481-491. Full Text PDF: Corticosteroids, But Not TNF Antagonists, Are Associated With Adverse COVID-19 Outcomes in Patients With Inflammatory Bowel Diseases: Results From an International Registry

“Surveillance Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD) is a large, international registry created to monitor outcomes of patients with IBD with confirmed COVID-19.”

Key findings:

  • 525 cases from 33 countries were reported (median age 43 years, 53% men)
  • Risk factors for severe COVID-19 among patients with IBD included increasing age (adjusted odds ratio [aOR], 1.04; 95% CI, 1.01–1.02), ≥2 comorbidities (aOR, 2.9; 95% CI, 1.1–7.8), systemic corticosteroids (aOR, 6.9; 95% CI, 2.3–20.5), and sulfasalazine or 5-aminosalicylate use (aOR, 3.1; 95% CI, 1.3–7.7).
  • Tumor necrosis factor antagonist treatment was not associated with severe COVID-19 (aOR, 0.9; 95% CI, 0.4–2.2)

Other COVID-19 articles from same journal:

My take: There is a tremendous amount of information regarding SARS-CoV-2 & COVID-19 with regard to the GI tract and liver disease.  For the most part, the data indicate that individuals need to continue to treat their underlying disease and that most therapies do not increase the risk of worsening infection; the biggest risk factors remain increasing age and common comorbidities (eg. obesity, hypertension, and diabetes).  The published studies also provide insight and recommendations for preventing SARS-CoV-2 for health care providers.

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Collagenous Gastritis

“Collagenous gastritis (CG) is a rare gastrointestinal disorder with fewer than 300 cases reported in the English-language literature.”  If you have to manage one of these rare cases, here is a useful reference:

Key points:
  • The prevalence of CG was 2.1/100,000 in children aged younger than 18 years
  • The endoscopic and histologic findings remained pathologic in all the examined patients during a median follow-up of 4.4 years
  • The serum levels of calprotectin and amyloid A were increased in 10/15 (67%) and 5/15 (33%) of the patients, respectively

Diagnostic Strategy For Children with Diarrhea and Abdominal Pain

A recent study (E Van de Vijver et al. Pediatrics 2020; 146: e20192235) shows a logical approach for testing children with diarrhea and abdominal pain.

Abstract and video abstract link: Test Strategies to Predict Inflammatory Bowel Disease Among Children With Nonbloody Diarrhea

Methods:

  • Prospective cohort study: n=193, 6 to 18 years who underwent a standardized diagnostic workup.
  • Patients with rectal bleeding or perianal disease were excluded because the presence of these findings prompted endoscopy regardless of their biomarkers.
  • In addition to symptoms, objective measures included C-reactive protein (>10 mg/L), hemoglobin (<−2 SD for age and sex), and fecal calprotectin (≥250 μg/g).

Key findings:

  • Twenty-two of 193 (11%) children had IBD
  • “Triaging with a strategy that involves symptoms, blood markers, and calprotectin will result in 14 of 100 patients being exposed to endoscopy. Three of them will not have IBD, and no IBD-affected child will be missed.

My take: The approach advocated by the authors of reserving a diagnostic endoscopy for children at high risk for IBD based on stool tests/blood tests in addition to symptoms has merit.  I would add a couple caveats:

  1. In this population, I would recommend checking for celiac disease (eg. tissue tranglutaminase IgA antibody, serum IgA level)
  2. I think in individuals with ‘borderline’ elevations of calprotectin (50-250 μg/g), followup testing is needed and if remains persistently elevated, then ileocolonoscopy is likely warranted.  (Calprotectin values in younger children tend to be higher -so this approach is best suited in children >5 years of age)

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Crohn’s Disease Anastomotic Ulcerations

A recent retrospective study (RP Hirten et al. Inflamm Bowel Dis 2020; 26: 1050-1058Anastomotic Ulcers After Ileocolic Resection for Crohn’s Disease Are Common and Predict Recurrence) showed that anastomotic ulcers occur in over half of Crohn’s disease patients after ileocolic resection and are associated with Crohn’s disease recurrence and are persistent.

Key findings:

  • Anastomotic ulcers were present in 95 (52.2%) subjects. No factors were associated with anastomotic ulcer development.
  • Anastomotic ulcers were associated with disease recurrence (adjusted hazard ratio [aHR] 3.64)

The associated editorial by Philllip Fleshner (pg 1059) identifies are a number of methodologic flaws, noting that less than 20% of all ileocolonic resections were included and marked variability in postoperative assessment (from 29 days to 2897 days).

My take: (borrowed from the editorial) the “findings should convince us that anastomotic ulcers do not represent ischemic changes but are rather a reflection of disease progression.”  Prospective studies with standardized surveillance would be helpful.

 

“Positioning Biologic Therapies in the Management of Pediatric Inflammatory Bowel Disease” & 14% of U.S. Infected with COVID-19

J Breton et al. Gastroenterology & Hepatology 2020; 16: 400-14. Full text: Positioning Biologic Therapies in the Management of Pediatric Inflammatory Bowel Disease

This is a terrific summary of biologic therapies for pediatric inflammatory bowel disease. Compared to adults, the pediatric data is much more limited.  This may affect recommendations.  For example, recent AGA guidelines for moderate to severe ulcerative colitis in adults suggests that either ustekinumab or tofacitinib is generally preferable as a 2nd line agent rather than vedolizumab in patients with primary infliximab failure (Blog post: AGA Guidelines: Moderate to Severe Ulcerative Colitis).  In the chart below, vedolizumab is recognized as a preferred 2nd line agent.

In the section on vedolizumab:

The favorable risk-benefit profile makes vedolizumab an ideal therapeutic choice for pediatric IBD. However, an important limitation is its delayed onset of action, for which corticosteroid use as bridge therapy is often necessary in this population that is already at increased risk of growth failure and bone loss. Recently, Hamel and colleagues published their small, single-center experience of using concomitant tacrolimus between anti-TNFα withdrawal to vedolizumab maintenance as a corticosteroid-sparing bridge therapy in moderate to severe IBD (Ref: Hamel B, Wu M, Hamel EO, Bass DM, Park KT. Outcome of tacrolimus and vedolizumab after corticosteroid and anti-TNF failure in paediatric severe colitis. BMJ Open Gastroenterol. 2018;5(1):e000195).

This article addresses therapeutic drug monitoring:

TDM is a key component of managing IBD patients on anti-TNFα therapy. While  reactive TDM of antiTNFα agents has been adopted by societal guidelines, there is an increasing body of literature to support the benefit of proactive TDM, particularly in pediatric populations

Conclusions from authors: Anti-TNFα agents have revolutionized the management of IBD, positively modifying the natural disease history in children. Importantly, inception cohort studies of pediatric CD and UC (RISK and PROTECT, respectively) have highlighted the variable course of disease and necessity of adopting an individualized approach with early use of biologic therapy in patients at risk of severe disease progression. 

Biologics Used in Pediatric Inflammatory Bowel Disease

Related blog posts:

Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  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

 

Hemospray Efficacy and Rebleeding

A Ofusu et al. J Clin Gastroenterol 2020. doi:10.1097/MCG.0000000000001379. The Efficacy and Safety of Hemospray for the Management of Gastrointestinal Bleeding

This systematic review and meta-analysis included 19 studies and 814 patients.

  • 212 patients were treated with Hemospray as monotherapy
  • 602 patients were treated with Hemospray with conventional hemostatic techniques.

Key findings:

  • Overall pooled clinical success after the application of Hemospray was 92%
  • Overall pooled early rebleeding rates (<7 days) after application of Hemospray was 20%
  • Overall pooled delayed rebleeding rates after the application of Hemospray was 23% (<30 days)
  • There was no statistical difference in clinical success (RR, 1.02; 95% CI, 0.96-1.08; P=0.34) and early rebleeding (RR, 0.89; 95% CI, 0.75-1.07; P=0.214) in studies that compared the use of Hemospray as monotherapy versus combination therapy with conventional therapy.

Related study: D Chahal et al. Dig Liver Dis 2020. DOI: https://doi.org/10.1016/j.dld.2020.01.009 Full text: High rate of re-bleeding after application of Hemospray for upper and lower gastrointestinal bleeds Findings (n=86): Immediate hemostasis rate was 88.4%, but there was a high rate of re-bleeding (33.7%). Most re-bleeds occurred within 7 days (86.2%)

My take: Hemospray is effective in achieving immediate hemostasis but there are high rates of rebleeding. It may be eliminated by GI tract in as few as 24 hours after use.  Thus, for lesions at high risk for bleeding, hemospray is likely more of a last resort endoscopic option.

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Eosinophilic Esophagitis -FAQs

A recent FAQ on Eosinophilic Esophagitis  Ronak Patel, MD  Ikuo Hirano, MD, AGAF: Full Text -GIHepNews (August 2020) Eosinophilic esophagitis: Frequently asked questions (and answers) for the early-career gastroenterologist

One aspect about this review that I liked was the dietary step-up –step-down therapy figure:

Reference: J Molina-Infante et al. J Allergy and Clincal Immunology. DOI:https://doi.org/10.1016/j.jaci.2017.08.038 Step-up empiric elimination diet for pediatric and adult eosinophilic esophagitis: The 2-4-6 study Results:  A TFGED (2-food) achieved EoE remission in 56 (43%) patients, with no differences between ages. Food triggers in TFGED responders were milk (52%), gluten-containing grains (16%), and both (28%). EoE induced only by milk was present in 18% and 33% of adults and children, respectively. Remission rates with FFGEDs (4-food) and SFGEDs (6-food) were 60% and 79%, with increasing food triggers, especially after an SFGED. Overall, 55 (91.6%) of 60 of the TFGED/FFGED responders had 1 or 2 food triggers. Compared with the initial SFGED, a step-up strategy reduced endoscopic procedures and diagnostic process time by 20%.

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