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.

Weak Link in Liver Transplantation Survival

Posted on December 8, 2016 by gutsandgrowth

A recent article and editorial (DH Leung et al. Liver Transpl 2016; 22: 1584-92 & editorial by JC Bucuvalas, S Feng 1466-68) provides a better picture of long-term survival for pediatric patients facing the prospect of liver transplantation.

Among patients less than 2 years in the UNOS data sharing registry, there were 994 with biliary atresia (BA) and 221 with other chronic liver disease.

The key data:

The overall postlisting mortality was 19.6% with most of this due to wait-list mortality (12.4%). Posttransplant mortality was 8%.
The non-BA patients had a higher wait-list mortality compared with BA patients: 23.9% vs 9.8%
Risk factors for mortality included lack of exception points (HR 5.8), and initial creatinine >0.5. In addition, BA patients without prior abdominal surgery (eg Kasai) was higher (risk was 1.6 times greater) than in those with BA with presumed Kasai.

Reviewing the article, it is not clear to me if patients removed the waitlist (eg due to sepsis and other causes) are included in this analysis. Thus, the true postlisting mortality may be higher than 20% if all needy individuals are considered.

From the editorial -other aspects:

Only one-third of pediatric recipients have optimal outcomes which would include normal LFTs, maintained on monotherapy immunosuppression, normal growth, and free of comorbidity. In addition, even among those with ‘optimal’ outcomes, many would still have histologic injury.
The “incidence of nonstandard exception requests has increased 5-fold and is now used on behalf of 44% of wait-listed children.” Importantly, children with public insurance were less likely to have petitions for exception PELD points.

My take (with help from editorial): To improve outcomes, this means starting with candidate selection and working on each step: traversing wait-list management and optimizing posttransplant care.

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Mural in Rockland, ME

Notable Briefs for IBD -December 2016

Posted on December 7, 2016 by gutsandgrowth

MI Abdalla et al. Inflamm Bowel Dis 2016; 22: 2658-64. This article reviewed the impact of an ostomy on QOL (quality of life) for Crohn’s disease patients. n=402 with ostomy compared with 4331 CD patients without.

Key findings:

Patients with ostomy were more likely to be in remission: 48.5% versus 31.35%.
Having an ostomy did not impact overall health-related quality of life but did reduce social role satisfaction.
Conclusion: “ostomy is well tolerated…particularly when clinical remission is achieved.”

WKM Liew et al. J Pediatr 2016; 178: 227-32. In this study with 16 patients (aged 6-24 years) who received thalidomide, more information on neuropathy is provided. “All subjects with cumulative doses greater than 60 g developed polyneuropathy.” 4 of 5 subjects receiving the drug for >20 months developed neuropathy. Two important points:

the severity of neuropathy plateaued (nonprogressive)
there are similar derivative drugs which do not appear to cause neuropathy: lenalidomide adnd pomalidomide
related blog posts: When nothing else is working | gutsandgrowth, Desperate measures in refractory IBD

V Collij et al. Inflamm Bowel Dis; 2016; 22: 2562-70. “We identified drugs that target the proteins encoded by IBD candidate genes.” Key finding: There were 113 drugs that could potentially be used in IBD treatment, including 14 known IBD drugs, 48 drugs that are/have been tested for IBD, 19 being tested for other inflammatory diseases, and 32 new investigational medications.

from one of the best days all year on board “Bufflehead”

Latest on Vedolizumab

Posted on December 6, 2016 by gutsandgrowth

A Amiot et al. Clin Gastroenterol Hepatol November 2016 Volume 14, Issue 11, Pages 1593–1601.

Abstract:

Background & Aims

Phase 3 trials have shown the efficacy of vedolizumab, which binds to integrin α4β7, in patients with Crohn’s disease (CD) or ulcerative colitis (UC). We investigated the effectiveness and safety of vedolizumab in patients who failed anti-tumor necrosis factor therapy.

Methods

From June through December 2014, there were 173 patients with CD and 121 patients with UC who were included in a multicenter nominative compassionate early access program granted by French regulatory agencies. This program provided patients with access to vedolizumab before it was authorized for marketing. Vedolizumab (300 mg) was administered intravenously at weeks 0, 2, and 6, and then every 8 weeks. Disease activity was assessed using the Harvey–Bradshaw Index for CD and the partial Mayo Clinic score for UC. We report results obtained after the 14-week induction phase.

Results

Among the 294 patients treated with vedolizumab (mean age, 39.5 ± 14.0 y; mean disease duration, 10.8 ± 7.6 y; concomitant steroids, 44% of cases), 276 completed the induction period, however, 18 discontinued vedolizumab because of a lack of response (n = 14), infusion-related reaction (n = 2), or infections (n = 2). At week 14, 31% of patients with CD were in steroid-free clinical remission and 51% had a response; among patients with UC, 36% were in steroid-free clinical remission and 50% had a response. No deaths were reported. Severe adverse events occurred in 24 patients (8.2%), including 15 (5.1%) that led to vedolizumab discontinuation (1 case of pulmonary tuberculosis and 1 rectal adenocarcinoma).

Conclusions

In a cohort of patients with CD or UC who failed previous anti–tumor necrosis factor therapy, approximately one third of patients achieved steroid-free clinical remission after 14 weeks of induction therapy with vedolizumab. This agent had an acceptable safety profile in these patients.

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Are Followup Biopsies Necessary for Celiac Disease? Look Beyond the Headline

Posted on December 5, 2016 by gutsandgrowth

A retrospective study from Boston has gained attention for suggesting that repeat biopsies may be needed for celiac disease (published online, MM Leonard et al JPGN, doi: 10.1097/MPG.0000000000001460). In my view, this may be a little early for that recommendation for asymptomatic patients with normal serology.

Full Abstract:

Value of IgA tTG in Predicting Mucosal Recovery in Children with Celiac Disease on a Gluten Free Diet.

Objective: Our objective was to determine the rate of mucosal recovery in pediatric patients with celiac disease on a gluten free diet. We also sought to determine whether IgA tissue transglutaminase (tTG) correlates with mucosal damage at the time of a repeat endoscopy with duodenal biopsy in these patients.

Methods: We performed a retrospective chart review of one-hundred and three pediatric patients, under 21 years of age, with a diagnosis of celiac disease defined as Marsh 3 histology, and who underwent a repeat endoscopy with duodenal biopsy at least twelve months after initiating a gluten free diet.

Results: We found that 19% of pediatric patients treated with a gluten free diet had persistent enteropathy. At the time of the repeat biopsy, tTG was elevated in 43% of cases with persistent enteropathy and 32% of cases in which there was mucosal recovery. Overall the positive predictive value of the autoantibody tissue transglutaminase was 25% and the negative predictive value was 83% in patients on a gluten free diet for a median of 2.4 years.

Conclusions: Nearly one in five children with celiac disease in our population had persistent enteropathy despite maintaining a gluten free diet and IgA tTG was not an accurate marker of mucosal recovery. Neither the presence of symptoms nor positive serology were predictive of a patient’s histology at the time of repeat biopsy. These findings suggest a revisitation of monitoring and management criteria of celiac disease in childhood.

Link to full text: A few other key points:

The most common indications for repeat endoscopy were due to persistent symptoms (43%) and new gastrointestinal symptoms (27%). Twenty-four subjects (34%) had persistently elevated serology at the time of the repeat biopsy.
19% exhibited persistent enteropathy consistent with a Marsh 3 lesion at the time of the repeat endoscopy.
Only 71 patients had serology within 4 months of repeat endoscopy, limiting the interpretation of the concordance of tTG value to histology

My take: I think it is premature to recommend routine followup biopsies in asymptomatic patients with normal serology. I think a prospective study will be helpful; the majority of patients in this study who underwent repeat biopsy were symptomatic and 9% were not adherent to their diet. Thus, this may not reflect a typical patient with celiac disease at followup. In addition, it would be helpful with regard to whether persistent histological findings have clinical significance.

Despite these limitations –this is how this article is being reported (from news-medical.net), here’s an excerpt from a recent summary:

Study finds 1 in 5 pediatric celiac disease patients on gluten-free diet sustain persistent intestinal damage

Alessio Fasano, MD, director of the MGHfC center and co-senior author of the study, was also surprised by the results, which were based on a retrospective examination of the biopsy and medical records of 103 children with celiac disease treated at MGHfC or BCH. The children had been on the gluten-free diet for at least one year and were determined by dietitians and other hospital health care practitioners to have complied well with the diet. But repeat biopsies found persistent intestinal damage in 19 percent of them. “The number of children who don’t heal on the gluten-free diet was much higher than what I expected,” Fasano says.

Image Only: Negative NSAIDs for Barrett’s Esophagus Study

Posted on December 4, 2016 by gutsandgrowth

Public Shaming is Not an Effective Drug Pricing Policy

Posted on December 3, 2016 by gutsandgrowth

From NBC News: Congress Doesn’t Scare Drug Execs Into Lowering Prices

Excerpt:

Congress’s routine of publicly shaming drug company executives over high prices works no better than a placebo: It may make some people feel better, but it doesn’t treat the problem…

But a review by The Associated Press of the list prices of nearly 30 brand-name medications and generic versions targeted by congressional investigators shows most haven’t budged since coming under federal scrutiny, according to figures from Truven Health Analytics.

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The Dark Cloud Inside the Silver Lining -What’s Really Going on with Hepatitis C Infection

Posted on December 2, 2016 by gutsandgrowth

Despite the flood of articles touting the success and costs of the new hepatitis C virus (HCV) treatments, direct-acting antivirals (DAA), currently hepatitis C remains more dangerous than HIV and it is likely to continue to exert a huge mortality and morbidity for at least three more decades in the United States.

One study and an associated editorial look into this subject further:

J Chhatwal et al. Hepatitis C Disease Burden in the United States in the Era of Oral Direct-Acting Antivirals. Hepatology 2016; 64: 1442-1450.
JM Pawlotsky. The End of the Hepatitis C Burden: Really?

In the study, the authors used a validated HCV burden simulation model (HEP-SIM) and noted the following:

“Even in the oral DAA era, 320,000 patients will die, 157,000 will develop hepatocellular carcinoma, and 203,000 will develop decompensated cirrhosis in the next 35 years.”

Part of the problems will be a large number of individuals who remain unaware of their diagnosis (560,000 by year 2020) but other barriers include medication costs.

From the editorial -some pushback on the cost-savings argument:

“Although current drug regimens were reported to be cost-effective, nothing justifies the current prices, except financial considerations on the drug makers’ side. On the one hand, one could consider that the money saved on liver disease-related expenses is not truly saved. Being cured from HCV and not dying from its complications will not prevent the same individual from dying from another cause at a very high cost.”

My take: To bend the HCV curve faster, there will need to be increased HCV screening, increased treatment capacity, and reasonable costs.

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Acadia Natl Park

Cool Microflora Translational Study with Celiac Disease

Posted on December 1, 2016 by gutsandgrowth

There has been a deluge of articles regarding the microbiome; yet, many aspects of microbiome derangements may have limited clinical significance. In addition, in many circumstances, it is not clear if the changes in the microbiome represent the proverbial chicken or the egg. How much of the changes in the microbiome are a consequence rather than a cause of a clinical problem?

One fascinating article (A Caminero et al. Gastroenterol 2016; 151: 670-83) looks at the role of the microflora with regard to gluten breakdown and immunogenicity. Thanks to Ben Gold who prompted me to take a 2nd look at this study.

In this study, the authors took bacteria isolated from the small intestines of Celiac disease (CD) patients or controls and colonized germ-free mice. Subsequently, “after gluten gavage, gliadin amount and proteolytic activities were measured” and characterized.

Key findings:

Pseudomonas aeruginosa isolated from CD patients “produced peptides that better translocated the mouse intestinal barrier.”
The P aeruginosa-modified gluten peptides activated gluten-specific T-cells from CD patients.
In contrast, Lactobacillus spp isolated from the duodenum of non-CD controls degraded gluten peptides and reduced their immunogenicity.

The others selected P aeruginosa from CD patients as it was not present in controls, though most strains were in fact within the phylum Firmicutes. Lactobacillus spp was chosen from the healthy subjects “because it constitutes a core resident group in the human small intestine that is involved in gluten metabolism in vitro and is altered in CD patients.”

Figure 2 specifies the distinct gluten metabolic patterns induced by the intestinal bacteria.
Figure 3-6 show numerous changes in the immunogenicity of gluten peptides induced the intestinal bacteria.

Overall, the study provides some evidence that changes in microbiome could trigger intestinal inflammation. Thus, since autoimmunity and celiac disease have an environmental trigger, this study implicates changes in the microflora as a risk factor for developing celiac disease in the susceptible host (see Figure 7 in the source article).

My take (from authors): This study identified “both pathogenic and protective microbe-gluten-host interactions that may modulate autoimmune risk in HLA-DQ2 susceptible persons.”

Acadia Natl Park

NASPGHAN Statement on High-Powered Magnet Court Ruling

Posted on November 30, 2016 by gutsandgrowth

NASPGHAN Statement on High-Powered Magnet Court Ruling

The North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) is shocked and deeply disappointed by the decision of the U.S. Court of Appeals for the Tenth Circuit to overturn the federal government’s strict safety standard for small, high-powered magnets. This legal ruling does not change the hazard these products pose to children.

Representing pediatric gastroenterologists who are on the front lines of treating children who accidentally ingest these magnets, NASPGHAN is calling on U.S. retailers, including online retailers, to boycott the sale of products that do not meet the safety standard for magnet sets issued by the Consumer Product Safety Commission in 2014.

Prior to the new safety standard, pediatric gastroenterologists witnessed a rise in the number of ingestions of high-powered magnets by toddlers and teenagers, often with severe medical consequences. These magnets were sold as part of magnet sets sold as desk toys.

Kids ingest a lot of things they shouldn’t. High-powered magnet ingestions are different than other ingested foreign bodies. Most foreign bodies will pass through the digestive tract without incident. When two or more magnets are ingested, their attractive force allows the magnets to “find” each other once inside the digestive tract. Consequently, there is a high risk of a fold of intestine becoming trapped between the magnets. When this occurs, ulceration and bowel perforation can occur and lead to death.

NASPGHAN recommends that high-powered magnet sets should not be stored or used in homes or other settings where children are present. Because these high-powered magnets often come in sets of 100 or more, missing magnets are not easily accounted for and can get lost in carpet or furniture where they can be found by small children.

Children should receive immediate medical attention for a known or suspected magnet ingestion. Consumers and health care providers are strongly encouraged to report incidents of ingestions to www.saferproducts.gov.

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Update on Chronic Cough

Posted on November 30, 2016 by gutsandgrowth

It is not uncommon for a pediatric gastroenterologist to see a patient with a chronic cough due to concerns about potential gastroesophageal reflux disease (GERD). As such, a recent clinical practice article (JA Smith, A Woodcock. NEJM 2016; 375: 1544-51) by lung specialists was of interest, even though this article was not targeted to the pediatric population.

Key points:

The authors define a chronic cough as lasting more than 8 weeks and note that it common with respiratory conditions (eg. chronic obstructive pulmonary disease, asthma, and bronchiectasis) and some non-respiratory conditions (eg. gastroesophageal reflux and rhinosinusitis). Medications, particularly ACE inhibitors, can trigger a chronic cough as well.
Steps in evaluation: 1. H&P, CXR, spirometry. 2. Consider metacholine challenge, ENT evaluation, consider empiric treatment (eg. inhaled glucocorticoids, PPI), and consider GERD evaluation. 3. High-resolution CT and bronchoscopy.
For many patients, there is likely to be an abnormality in neuronal pathways controlling cough and the term “cough hypersensitivity syndrome” has been coined. Figure 2 (below) illustrates the neuronal pathways.
For refractory patients, potential therapies would include low-dose morphine, gabapentin or pregabalin, and speech language therapy.

GERD:

Guidelines “suggest a trial of treatment with acid-suppression therapy” (eg. twice-daily PPIs for up to 3 months).
“Most randomized, controlled trials of reflux treatment for cough have not shown a significant improvement in association with this type of treatment.”
Subgroups of patients with heartburn, regurgitation, or excessive acid reflux on esophageal pH monitoring “appeared marginally more likely to have a response to PPI treatment.” pH or impedance tests “are poorly predictive of a response of cough to acid suppression.”

My take: In the absence of clinical reflux, reflux therapy is unlikely to help with chronic cough. However, in patients with an adequate workup, an empiric course of a PPI is likely more preferable than empiric morphine or gabapentin.

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