Author Archives: gutsandgrowth

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About gutsandgrowth

I am a pediatric gastroenterologist at GI Care for Kids (previously called CCDHC) in Atlanta, Georgia. The goal of my blog is to share some of my reading in my field more broadly. In addition, I wanted to provide my voice to a wide range of topics that often have inaccurate or incomplete information. Before starting this blog in 2011, I would tear out articles from journals and/or keep notes in a palm pilot. This blog helps provide an updated source of information that is easy to access and search, along with links to useful multimedia sources. I was born and raised in Chattanooga. After graduating from the University of Virginia, I attended Baylor College of Medicine. I completed residency and fellowship training at the University of Cincinnati at the Children’s Hospital Medical Center. I received funding from the National Institutes of Health for molecular biology research of the gastrointestinal tract. During my fellowship, I had the opportunity to work with some of the most amazing pediatric gastroenterologists and mentors. Some of these individuals included Mitchell Cohen, William Balistreri, James Heubi, Jorge Bezerra, Colin Rudolph, John Bucuvalas, and Michael Farrell. I am grateful for their teaching and their friendship. During my training with their help, I received a nationwide award for the best research by a GI fellow. I have authored numerous publications/presentations including original research, case reports, review articles, and textbook chapters on various pediatric gastrointestinal problems. In addition, I have been recognized by Atlanta Magazine as a "Top Doctor" in my field multiple times. Currently, I am the vice chair of the section of nutrition for the Georgia Chapter of the American Academy of Pediatrics. In addition, I am an adjunct Associate Clinical Professor of Pediatrics at Emory University School of Medicine. Other society memberships have included the North American Society for Pediatric Gastroenterology Hepatology and Nutrition (NASPGHAN), American Academy of Pediatrics, the Food Allergy Network, the American Gastroenterology Association, the American Association for the Study of Liver Diseases, and the Crohn’s and Colitis Foundation. As part of a national pediatric GI organization called NASPGHAN (and its affiliated website GIKids), I have helped develop educational materials on a wide-range of gastrointestinal and liver diseases which are used across the country. Also, I have been an invited speaker for national campaigns to improve the evaluation and treatment of gastroesophageal reflux disease, celiac disease, eosinophilic esophagitis, hepatitis C, and inflammatory bowel disease (IBD). Some information on these topics has been posted at my work website, www.gicareforkids.com, which has links to multiple other useful resources. I am fortunate to work at GI Care For Kids. Our group has 17 terrific physicians with a wide range of subspecialization, including liver diseases, feeding disorders, eosinophilic diseases, inflammatory bowel disease, cystic fibrosis, DiGeorge/22q, celiac disease, and motility disorders. Many of our physicians are recognized nationally for their achievements. Our group of physicians have worked closely together for many years. None of the physicians in our group have ever left to join other groups. I have also worked with the same nurse (Bernadette) since I moved to Atlanta in 1997. For many families, more practical matters about our office include the following: – 14 office/satellite locations – physicians who speak Spanish – cutting edge research – on-site nutritionists – on-site psychology support for abdominal pain and feeding disorders – participation in ImproveCareNow to better the outcomes for children with inflammatory bowel disease – office endoscopy suite (lower costs and easier scheduling) – office infusion center (lower costs and easier for families) – easy access to nursing advice (each physician has at least one nurse) I am married and have two sons (both adults). I like to read, walk/hike, bike, swim, and play tennis with my free time. I do not have any financial relationships with pharmaceutical companies or other financial relationships to disclose. I have helped enroll patients in industry-sponsored research studies.

Liver Briefs May 2017

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Briefly noted:

O Jeanniard-Malet et al. JPGN 2017; 64: 524-7. This survey of 28 centers in France assessed clinical practice with regard to primary prophylaxis in portal hypertension. More than 75% use endoscopy to screen for varices in patients with chronic liver conditions. “In cases of grade 2 varices with red marks and grade 3 varices >90% of centres perform sclerotherapy or endoscopic variceal ligation.”

Y-D Ren et al. Hepatology 2017; 65: 1765-8. FMT for chronic HBV? This small study with 5 patients who received fecal microbiota transplantation in an effort to clear HBeAg.  There were 13 controls.  Patients in both group received either ongoing entecavir or tenofovir antiviral therapy (& had received for at least 3 years). FMT was given every 4 weeks (1 to 7 treatments). HBeAg declined gradually after each round.  Three patients in the FMT arm cleared HBeAg compared with none in the control arm.  Two of the three cleared HBeAg after on FMT and the third after two rounds of FMT.

Y Sun et al. Hepatology 2017; 65: 1438-50.  In this report, the authors propose to augment the liver biopsy classification in patients with Hepatitis B.  Their goal is to provide more information about dynamic changes regarding fibrosis using three terms:

  • Predominantly progressive: thick/broad/loose/pale septa with inflammation
  • Predominantly regressive: delicate/thin/dense/splitting septa
  • Indeteminate

Using this new designation, they characterized 71 paired liver biopsies before and after entecavir for 78 weeks.  Before treatment: 58%, 29%, and 13% for progressive, regressive and indeterminate; after treatment: 11%, 11%, and 78% respectively.

Rodin Museum, Gates of Hell

 

Brain-Gut Axis in 2017

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“Brain–gut interactions and maintenance factors in pediatric gastroenterological disorders. Recommendations for clinical care.” B Reed-Knight et al. Clinical Practice in Pediatric Psychology, 2017; 5: 93-105.

A summary of this review article by Sharon Berry, PhD, ABPP, Past President, Society of Pediatric Psychology:

This review article describes the brain–gut axis as a means to increase understanding of how biological mechanisms implicated in a range of pediatric GI disorders interact with psychological and contextual factors to maintain GI symptoms and (b) provide practical ways for pediatricians and other healthcare providers to  incorporate a discussion of the brain–gut axis into patient education for pediatric GI disorders.

Biological mechanisms of the brain–gut axis including alterations in pain processing, the stress response system, and gut microbiome activity are reviewed. Psychosocial factors that contribute to or maintain disturbances in the brain–gut axis are discussed with implications for clinical assessment and intervention. The authors assert that a mutual understanding by patients, families, and providers alike of the relevant brain–gut interactions and the biopsychosocial model, in general, will serve as a foundation for successful delivery of and adherence to medical and psychological interventions. Important clinical conclusions include:

  • Early discussion of the brain-gut axis may reduce resistance to integrated behavioral or psychological treatment for pediatric gastroenterological disorders.
  • Sample visual aids and descriptive scripts are available within this review to guide discussions of the brain-gut axis with patients and families for a range of pediatric GI disorders.

My take: This article serves is a useful resource for pediatric psychologists to better understand the ideas of visceral hypersensitivity, stress response, and biological triggers (eg. gut microbiome, infections) for gastrointestinal disorders. Its discussion of biopsychosocial assessment and psychological interventions are helpful for pediatric gastroenterologists to understand the psychological approaches toward treatment.

Related blog posts:

NPR: Banana Diet for Celiac Disease

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A recent report from NPR highlights a previous diet for celiac disease -the banana diet. While celiac disease had been discovered in the 1890s by Dr. Samuel Gee, the role of gluten was not understood until WWII.

NPR: Doctors Once Thought Bananas Cured Celiac Disease

Here’s an excerpt:

a high-calorie, banana-based diet [was] invented by Dr. Sidney Haas in 1924. The diet forbade starches but included numerous daily bananas, along with milk, cottage cheese, meat and vegetables…

Haas arrived at his banana diet through an honest error — one that, unfortunately, had serious repercussions for people with celiac disease. In his 1924 paper, he wrote of a town in Puerto Rico where “dwellers who eat much bread suffer from [celiac] sprue while the farmers who live largely on bananas never.”

Haas skipped over the role of wheat and focused instead on the exotic bananas, which he thought held curative powers…

But Haas’ honest error led to serious consequences. As the children recovered, wheat was reintroduced.

It was a Dutch pediatrician, Willem Karel Dicke, who first realized that wheat might be linked to celiac disease. He noticed that in the last few years of World War II, when bread was unavailable in the Netherlands, the mortality rate from celiac disease dropped to zero. In 1952, Dicke and his colleagues identified gluten as the trigger for celiac disease, and the gluten-free diet was born.

 

Vaccine for Celiac Disease

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A recent study (KM Kemppainen et al. Clin Gastroenterol Hepatol 2017; 15: 694-702, editorial 703-5) showed that gastrointestinal infections can trigger celiac disease (CD) and that immunization with the rotavirus vaccine was protective against developing CD.

This study is part of the TEDDY study: The Environmental Determinants of Diabetes in the Young.  The TEDDY cohort involves more than 8000 children who are part of an international prospective cohort who carry genes (HLA-DR-DQ genotypes) with increased risk for diabetes and CD. In this particular group, the authors identified 6327 children who were 4 yrs old by March 2015.

Key Definition: CD autoimmunity (CDA) -children who tested positive for tTG IgA at their annual visit and remained persistently positive 3 months later

Key Findings:

  • Gastointestinal infections (n=13,881) but not respiratory infections (n=79,816) were associated with an increased risk of CDA.  CDA risk was increased within the 3 months of the GI infection.
  • 732 of 6327 (11.6%) developed CDA.  In this cohort, 318 underwent duodenal biopsy and 283 (90%) had biopsy indicative of CD (Marsh score >1). Thus, in their cohort, there is variability in the onset of CD from the onset of CDA.
  • Risk of CDA was reduced in children vaccinated against rotavirus and introduced to gluten before age 6 months (HR =0.57).
  • The exact risk depending on interaction with multiple factors including breastfeeding, HLA genotype, seasonality of birth, and timing of gluten introduction. Timing of infection plays a role as well, as earlier exposure to GI infections earlier in life was associated with a decreased risk of celiac disease.

This reference should be kept handy for vaccine advocates.  Not only can vaccines prevent infections, but they have now been shown to prevent an autoimmune disease (CD).  In addition, previous studies have shown that vaccines can prevent cancers, including hepatocellular carcinoma and cervical cancer.

My take (modified from editorial): This study “demonstrates the power of rigorously conducted prospective studies to reveal complex interactions among genetic and environmental factors.” In addition, this study shows that preventing rotavirus infection with vaccination lowers the risk of celiac disease.

Related blog posts:

SuperPoopers CCFA Team 2017

IBD Resources for Clinicians/IBD Tweets

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Another website with a few useful resources:

  • Steroid taper calendar -helps develop a calendar (can use to print out or take a picture)
  • Imaging risk calculator -this is not that great.  In essence if you have a patient present to ER with a CRP of 1 mg/dL and ESR of 20, it states that risk of a complication like a perforation is “NOT LOW” and to consider imaging
  • IBD School Video collection -links to UM website

Note -therapeutic drug monitoring may be more useful in children due to their changing size.

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  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.

Tofacitinib Induction and Maintenance for Ulcerative Colitis

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W Sandborn et al. N Engl J Med 2017; 376:1723-1736 May 4, 2017DOI: 10.1056/NEJMoa1606910

Abstract from NEJM:

BACKGROUND

Tofacitinib, an oral, small-molecule Janus kinase inhibitor, was shown to have potential efficacy as induction therapy for ulcerative colitis in a phase 2 trial. We further evaluated the efficacy of tofacitinib as induction and maintenance therapy.

 

METHODS

We conducted three phase 3, randomized, double-blind, placebo-controlled trials of tofacitinib therapy in adults with ulcerative colitis. In the OCTAVE Induction 1 and 2 trials, 598 and 541 patients, respectively, who had moderately to severely active ulcerative colitis despite previous conventional therapy or therapy with a tumor necrosis factor antagonist were randomly assigned to receive induction therapy with tofacitinib (10 mg twice daily) or placebo for 8 weeks. The primary end point was remission at 8 weeks. In the OCTAVE Sustain trial, 593 patients who had a clinical response to induction therapy were randomly assigned to receive maintenance therapy with tofacitinib (either 5 mg or 10 mg twice daily) or placebo for 52 weeks. The primary end point was remission at 52 weeks.

 

RESULTS

In the OCTAVE Induction 1 trial, remission at 8 weeks occurred in 18.5% of the patients in the tofacitinib group versus 8.2% in the placebo group (P=0.007); in the OCTAVE Induction 2 trial, remission occurred in 16.6% versus 3.6% (P<0.001). In the OCTAVE Sustain trial, remission at 52 weeks occurred in 34.3% of the patients in the 5-mg tofacitinib group and 40.6% in the 10-mg tofacitinib group versus 11.1% in the placebo group (P<0.001 for both comparisons with placebo). In the OCTAVE Induction 1 and 2 trials, the rates of overall infection and serious infection were higher with tofacitinib than with placebo. In the OCTAVE Sustain trial, the rate of serious infection was similar across the three treatment groups, and the rates of overall infection and herpes zoster infection were higher with tofacitinib than with placebo. Across all three trials, adjudicated nonmelanoma skin cancer occurred in five patients who received tofacitinib and in one who received placebo, and adjudicated cardiovascular events occurred in five who received tofacitinib and in none who received placebo; as compared with placebo, tofacitinib was associated with increased lipid levels.

 

CONCLUSIONS

In patients with moderately to severely active ulcerative colitis, tofacitinib was more effective as induction and maintenance therapy than placebo.

Heroin Epidemic Causing Surge in Hepatitis C Infections

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From NPR: Heroin Epidemic is Driving a Spike in Hepatitis C Cases

An excerpt:

The number of new Hepatitis C cases leaped nearly 300 percent from 2010 to 2015, according to a report released Thursday by the Centers for Disease Control and Prevention. And the CDC points to the likely culprit behind the spike in cases of the infectious disease: the use of heroin and other injection drugs.

And despite the existence of therapies that can cure more than 90 percent of infections, the organization says the disease remains a deadly threat. In 2013, for instance, the CDC says some 19,000 people died of their infections.

From CNN: New Hepatitis C Infections Triple due to Opioid Epidemic

The number of new nationally reported infections with the virus swelled from 850 in 2010 to 2,436 cases in 2015, with the highest rates among young people, mainly 20- to 29-year-olds, who inject drugs, according to a new report released Thursday by the Centers for Disease Control and Prevention.

NPR: Safety Problems in 1/3rd of New Medications

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From NPR: Safety Problems in 1/3rd of New Medications After FDA Approval

From 2001-2010:

Seventy-one of the 222 drugs approved in the first decade of the millennium were withdrawn, required a “black box” warning on side effects or warranted a safety announcement about new risks to the public, Dr. Joseph Ross, an associate professor of medicine at Yale School of Medicine and colleagues reported in JAMA on Tuesday. The study included safety actions through Feb. 28…

It took a median of 4.2 years after the drugs were approved for these safety concerns to come to light, the study found, and issues were more common among psychiatric drugs, biologic drugs, drugs that were granted “accelerated approval” and drugs that were approved near the regulatory deadline for approval…

“In the 21st Century Cures Act, there’s a push to have the FDA move to further support the use of surrogate markers … [but] they’re more likely to have concerns in the post-market setting.”…

The study included market withdrawals of three drugs: The anti-inflammatory drug Bextra; a drug called Zelnorm that was used to treat irritable bowel syndrome; and the psoriasis drug Raptiva. Bextra and Zelnorm were withdrawn over cardiovascular risk, and Raptiva was withdrawn because of increased risk of a rare and fatal infection that causes brain damage.

My take: FDA approval does not guarantee safety.  All medications have potential risks along with their benefits.

 

Update: Florida Physician Gag Rule Overturned

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In a previous blog post, Politics and Limiting Physician Speech, I discussed the Florida Gag Rule intended to prevent physicians from discussing firearm safety with patients. At the time, I expressed outrage that “there are laws curtailing a physician’s free speech and efforts to dictate practice based on political philosophy.”

It looks my views have been vindicated.  NEJM report (full text): Physicians, Firearms, and Free Speech

An excerpt:

In February, the full U.S. Court of Appeals for the Eleventh Circuit issued its long-awaited ruling in Wollschlaeger v. Governor, State of Florida, invalidating parts of Florida’s Firearm Owners’ Privacy Act (FOPA) and affirming that the First Amendment applies to the speech between physicians and patients. The decision ensures that physicians may continue to make efforts to protect their patients from gun-related injuries, many of which are fatal and which in aggregate account for approximately as many deaths annually as do motor vehicle accidents….

the majority affirmed that laws regulating physician speech must be designed to enhance rather than harm patient safety. The majority took this mandate seriously and required the state to show some meaningful evidence that the regulation was apt to serve the state’s interest in protecting patients.

The state could not do so for two reasons. First, the decision to keep a gun in the home substantially increases the risk of death for all household members, especially the risk of death by suicide, and particularly so when guns are stored loaded and unlocked, as they are in millions of homes where children live.3 Second, the majority of U.S. adults who live in homes with guns are unaware of the heightened risk posed by bringing guns into a home.4 Indeed, by providing accurate information about the risks created by easy access to firearms, as well as ways to modify that risk (e.g., by storing guns unloaded and locked up, separate from ammunition), a physician’s counseling can not only enhance a patient’s capacity for self-determination, but also save lives…

The fact is that most clinicians, including those who routinely encounter suicidal patients, rarely, if ever, provide firearm-safety counseling.5 This reticence predated the FOPA and has persisted since its passage..The court has done its duty. It’s now the physicians’ turn.

Related blog posts:

Capers Island