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.

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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Treatment Outcomes in Children and Adolescents with Hypercholesterolemia

Posted on November 29, 2016 by gutsandgrowth

A recent study (MM Mendelson et al. J Pediatr 2016; 178: 149-55) provides some useful data indicating that statin therapy for children and adolescents is typically effective based on cholesterol reduction levels.

This observational study prospectively collected data from 2010-2014 among 1521 pediatric patients seen for a lipid disorder. In this cohort, 1260 patients (83%) did not receive statin therapy during the study period. Ultimately, 97 patients (6% of clinic cohort) had received statin therapy and had adequate data for evaluation.

70 patients received simvastatin: 1 at 5 mg/day, 26 at 10 mg/day, and 43 for 20 mg/day.
24 patients received atorvastatin: 22 at 10 mg/day and 2 at 20 mg/day
3 patients received pravastatin: 2 at 10 mg/day and 1 at 20 mg/day

Primary outcome for therapy: LDL-C <130 for patients without high risk factors and <110 for patients with high risk condition(s) (eg. diabetes mellitus, end-stage renal disease, heart transplant, Kawasaki disease with aneurysms)

Key findings:

Median baseline LDL-C was 215.
LDL-C decreased by 37% on average (83 mg/dL) within the first 60 days of therapy
Achieved primary outcome: 60% at 1 year, 73% at 2 years, and 87% at 3 years
No patients presented with relevant hepatic or myopathic side effects. 2 of 97 had transient epiosde of ALT > 3 x ULN.

Discussion:

Overall, the reported outcomes in this select cohort were at least as good as outcomes reported in studies of adults in the general population. This may be due to parental supervision or perhaps due to a better physiologic response. In addition, as this was an observational study, poorly adherent patients may be lost to follow-up and would not be accounted for.
Currently statin therapy is recommended if lifestyle modifications are not sufficient to lower LDL-C. Thus, “it is estimated that more than 700,000 US children and adolescents may be eligible for statin therapy according to the 2011 NHLBI guidelines.”

My take: Since cholesterol and LDL-C are biomarkers of treatment, the long-term benefit (& possible risks) of statin therapy remains unclear . However, more data on meaningful endpoints like heart attacks and strokes could take decades. Until then, the best evidence available suggests that the potential benefit of statin therapy could be quite substantial.

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HCV Treatment: Nearing 100% Effectiveness

Posted on November 28, 2016 by gutsandgrowth

While access to HCV treatment remains the biggest obstacle, recent studies show that the rates of HCV eradication, even in the toughest cases, now approaches 100%.

E Lawitz et al. Gastroenterol 2016; 151: 893-901.
EJ Gane et al. Gastroenterol 2016; 151: 902-9.
Editorial: M Buti pgs 795-8.

Most prior studies examined the use of two direct-acting antivirals (DAAs) with or without ribavirin. These DAAs targeted nonstructural (NS) proteins necessary for HCV replication: NS3 protease, NS5B polymerase, and NS5A protein.

These two new studies examined whether treatment with a DAA targeting all 3 NS proteins would be effective and possibly allow shorter treatments. It is noted that currently only treatment-naive genotype 1 (w/o cirrhosis) patients have a regimen that is recommended for only 8 weeks; these patients also should have HCV-RNA<6,000,000 IU/mL.

Lawitz et al studied the combination of sofosbuvir-velpatasvir and GS-9857 (voxilaprevir) for 6-8 weeks (one treatment group received ribavirin); n=197. Among treatment-naive patients w/o cirrhosis, SVR12 was 100% after 8 weeks of treatment and 94% of treatment-naive patients with cirrhosis. Among treatment-experienced patients treated for 12 weeks, 100% of all patients (w and w/o cirrhosis) achieved SVR12.

Gane et al studied the effectiveness of the combination of sofosbuvir-velpatasvir and GS-9857 in HCV genotypes 2, 3, 4, and 6 (as well as 1 with 1b); n=128. After 8 weeks of treatment, SVR12s were achieved in 93% of treatment-naive patients with cirrhosis. After 12 weeks, treatment-experienced patients with and without cirrhosis had SVR12s of 97% and 100% respectively.

My take: This combination of therapies should allow shorter treatment regimens in treatment-naive patients and effective rescue therapy for previous DAA failures. Now that we can cure almost everyone with HCV, how do make therapies affordable and accessible?

Glacier Nat’l Park

Severe Hypothyroidism due to Iodine Deficiency Associated with Parenteral Nutrition

Posted on November 27, 2016 by gutsandgrowth

From Kipp Ellsworth Twitter Feed:

J Parenter Enteral Nutr November 2016 vol. 40 no. 8 1191-1193

Abstract:

Parenteral nutrition is crucial for supply of nutrients in children who cannot tolerate a full enteral diet. In the United States, it is not standard of care to give iodine to children dependent on parenteral nutrition, hence iodine is not routinely included in the micronutrient package. Herein, we present a case of a boy with hypothyroidism secondary to iodine deficiency after prolonged exclusive use of parenteral nutrition. Our case highlights the importance of screening for iodine deficiency and administering timely iodine supplementation in these at-risk children to prevent iatrogenic hypothyroidism.

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