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.

High Endoscopy Complication Rate After Intestinal Transplantation

Posted on January 14, 2016 by gutsandgrowth

A recent study (J Yeh et al. JPGN 2015; 61: 636-40) indicated a high rate of endoscopy complications in pediatric patients who have undergone intestinal transplantation.

Key points:

Complications: In this single-center study with 1770 endoscopies (1014 sessions), the serious GI complication rate was 1.8% (32/1770). The complications included 11 GI perforations, 13 GI bleeds, 6 GI hematomas, 1 gastric mucosa avulsion, and 1 distention from retained air. The authors’ database was not designed to capture cardiopulmonary complications.
In comparison, the authors note that adults without intestinal transplantation have an estimated a perforation rate of 0.09% and serious complication rates (GI and non-GI complications) of 0.15% for upper endoscopy and of 0.2% for colonoscopy. In addition, a large pediatric study of non-transplant patient endoscopies, found a perforation rate of 0.014% for EGDs and 0.028% for colonoscopies. Thus, the authors are reporting a perforation rate (11 of 1770) that is more than 20-fold higher than this pediatric study’s colonoscopy perforation rate.
Their techniques are well-described. For example, “for ileoscopies, 2 to 3 sites each consisting of 2 to 3 biopsies were also taken every 5 to 10 cm from the distal graft…typically surveyed up to 50 to 60 cm from the ostomy or ileocolonic anastomosis.”
The reasons for endoscopy were most frequently related to diarrhea/stool output in 35% and for surveillance in 32%.
The other interesting finding was that “of histology-proven rejections, 45% had normal-appearing endoscopies.”

The authors recommend that patients with intestinal transplantation should have endoscopy at a specialized center with teams who are intimately familiar with these children.

My take: I worry that the high complication rates reported at this center may indicate that individuals (perhaps in training) who are less familiar with the patient’s anatomy are performing many of these endoscopies. I think individuals very familiar with the patient’s anatomy are best-suited to perform these endoscopies; this may limit some individuals at these specialized centers and may include some skilled endoscopists outside of intestinal transplant centers.

Related blog post: Something Bad is Going to Happen | gutsandgrowth

Galapagos

PPIs Alter the Microbiome

Posted on January 13, 2016 by gutsandgrowth

A couple of comments –today’s blog (below) and yesterday’s blog both point out potential concerns with proton pump inhibitors (PPIs). There is a danger that when publications emphasize the potential consequences of PPI use (including NPR’s recent piece on kidney disease and PPIs) that physicians and families will overlook the value of these medications.

With regard to the benefits of PPIs, there are a large number of studies supporting the effectiveness of PPIs for various GI conditions. As a result, there is little being published on drug effectiveness at this time. On a daily basis, these medications prevent a great deal of suffering, heal esophagitis, heal ulcers and contribute to improved health. If one looks only at the negative side of the ledger, this could create harm.

My personal belief is that when PPIs are used, that it is important to consider both the advantages and the disadvantages. If the benefits are unclear, this increases the necessity of evaluating the risks, especially in vulnerable populations. In addition, when the benefits are unclear, determining the length of therapy and/or performing appropriate diagnostic workup becomes essential.

Also, for pediatric gastroenterologists reading this blog, it is important to realize that my blog’s following is tiny in comparison to the circulation of the Journal of Pediatrics and news organizations like NPR. Therefore, we need to engage our pediatrician/family medicine colleagues to help make sure that PPIs are used effectively. I am looking forward to the January 26 NASPGHAN webinar on this topic.

——–

The degree to which proton pump inhibitors (PPIs) affect the gut microbiome is unclear. A recent study of 12 healthy volunteers (DE Freedberg et al. Gastroenterol 2015; 149: 883-85, Clearing Out My Desk | gutsandgrowth) indicated that this was not much; however, an even more recent study (F Imhann et al. Gut 2015 December 9 (Gut doi:10.1136/gutjnl-2015-310376)) suggests otherwise (abstract below) -their conclusion: “On a population level, the effects of PPI are more prominent than the effects of antibiotics or other commonly used drugs.”

Link: Proton pump inhibitors affect the gut microbiome

Abstract

BACKGROUND AND AIMS: Proton pump inhibitors (PPIs) are among the top 10 most widely used drugs in the world. PPI use has been associated with an increased risk of enteric infections, most notably Clostridium difficile. The gut microbiome plays an important role in enteric infections, by resisting or promoting colonisation by pathogens. In this study, we investigated the influence of PPI use on the gut microbiome.

METHODS: The gut microbiome composition of 1815 individuals, spanning three cohorts, was assessed by tag sequencing of the 16S rRNA gene. The difference in microbiota composition in PPI users versus non-users was analysed separately in each cohort, followed by a meta-analysis.

RESULTS: 211 of the participants were using PPIs at the moment of stool sampling. PPI use is associated with a significant decrease in Shannon’s diversity and with changes in 20% of the bacterial taxa (false discovery rate <0.05). Multiple oral bacteria were over-represented in the faecal microbiome of PPI-users, including the genus Rothia (p=9.8×10(-38)). In PPI users we observed a significant increase in bacteria: genera Enterococcus, Streptococcus, Staphylococcus and the potentially pathogenic species Escherichia coli.

CONCLUSIONS: The differences between PPI users and non-users observed in this study are consistently associated with changes towards a less healthy gut microbiome. These differences are in line with known changes that predispose to C. difficile infections and can potentially explain the increased risk of enteric infections in PPI users. On a population level, the effects of PPI are more prominent than the effects of antibiotics or other commonly used drugs.

My take: It is likely that the effects on the microbiome are even more notable in infants/younger children; in neonates, the changes in the microbiome could increase the risk of serious diseases like necrotizing enterocolitis.

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Yosemite

The Prosecution Rests…PPIs on Trial

Posted on January 12, 2016 by gutsandgrowth

For physicians who use proton pump inhibitors in a cavalier manner, a recent review (CM Stark, CM Nylund. J Pediatr 168: 16-22) provides a sobering reassessment of the potential side effects and potential complications of proton pump inhibitors (PPIs). After finishing the article, the impression left was of a lawyer putting these medications on trial for high crimes and misdemeanors.

Here were the key points:

Infectious disease: PPI-induced hypochloridia is known to alter the gastrointestinal bacteria motif, allowing certain normally absent or depleted pathogenetic microorganisms to survive and proliferate. This can lead to all of the following:

small bowel bacterial overgrowth
increased gastrointestinal infections (including Clostridium difficile, Salmonella, Campylobacter, and acute viral gastroenteritis)
pneumonia (particularly community acquired pneumonia and hospital acquired pneumonia)
upper respiratory infections
spontaneous bacterial peritonitis.

The magnitude of these associations is discussed in detail in the review.

Gastrointestinal disease: Use of PPIs has been associated with an increased incidence of the following:

celiac disease which persisted after excluding prescriptions in the year preceding diagnosis (association does not prove causation)
benign gastric fundic polyps
rebound acid hypersecretion

Malabsorption: PPIs can affect absorption of multiple nutrients, though more studies are needed, particularly in the pediatric age group.

calcium: “there is significant evidence to suggest that PPI use can alter calcium and bone metabolism…associated with an increased risk of hip fractures in older adults….It is reasonable to hypothesize that PPI administration during adolescence and early adulthood could decrease an individual’s peak bone density.”
magnesium: PPI have been hypothesized to affect magnesium absorption. “A study of 366 Canadian patients hospitalized with hypomagnesemia…found PPIs [were] associated with a 43% increased risk of hospitalization.” More studies are needed to determine the whether this risk is truly significant.
iron, vitamin B12, and vitamin C absorption may be affected by PPI use.

Cardiovascular/Renal/Microbiome:

Cardiac: In adults, PPI use has been associated with adverse cardiac events. The pathophysiology could have been pediatric implications. PPIs can increase asymmetrical dimethylarginine (ADMA) which is an endogenous inhibitor of nitric oxide synthase.
Renal: PPIs have been associated with cases of acute interstitial nephritis
Microbiome: “PPIs alter the microbiome.” Decreased diversity of the microbiome has been associated with a large number of medical conditions, including irritable bowel syndrome, inflammatory bowel disease, nonalcoholic fatty liver disease, necrotizing enterocolitis as well as many non-gastrointestinal conditions. “The temporality of dysbiosis and subsequent disease development has not been explored fully for most conditions.”

My take: PPIs can be life-saving and disease-altering medications. At the same time, (per authors) “PPIs should not be prescribed without consideration for all short- and long-term side effects.”

Related blog posts:

This Webinar Will Review Issues with Regard to Optimal PPI Usage and Includes My Esteemed Colleagues (Dr. Gold and Dr. Garza)

This NASPGHAN Webinar Will Review Issues with Regard to Optimal PPI Usage and Includes My Esteemed Partners (Dr. Gold and Dr. Garza)

Chronic Hepatitis B in North American Children

Posted on January 11, 2016 by gutsandgrowth

As part of the Hepatitis B Research Network (HBRN), 343 children were enrolled in 7 U.S. and Canadian centers. A recent study (KB Schwarz et al. J Pediatr 2015; 167: 1287-94) provides data on HBV epidemiology and a related commentary by Brian McMahon (1186-7) provides some useful advice on what is needed to further reduce HBV infection.

88 children were not enrolled. More than half of these patients refused to participate, the other reasons included language barriers or inability to comply with follow-up.

Key findings:

78% of the subjects in this study were Asian
55% were adopted. This high adoption rate likely skews some of the data because (according to the associated editorial) “children with HBV in the US..most are likely to be children of parents who immigrated to the US from endemic countries and not adoptees.”
97% had international origins with either the child or a parent born abroad
HBV genotype B was most common (43%) followed by genotype C (32%), D (16%), A (5%), E (4%) or multiple (<1%).

In the editorial, Dr. McMahon notes that ascertaining the rate of a birth dose of HBV vaccine would be of interest. In many countries, vaccination is started at ≥2 months and this is unlikely to prevent HBV transmission. Two important public health issues for North America:

“First, all pregnant women, especially those foreign-born, need to be screened for HBsAg and if positive, their infants should receive HBV vaccine and hepatitis B immune globulin immediately after birth.”
“Second, all foreign-born children and adults who immigrate to the US or Canada should be tested for HBsAg.”

My take: This study provides an up-to-date snapshot of tertiary care for children with HBV in North America. There are many opportunities to curtail (or hopefully eliminate) the impact of HBV in our communities and around the world.

AASLD Guideline (Nov 2015): Treatment of Chronic HBV

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San Diego Zoo

“Good Job Making the Diagnosis”

Posted on January 10, 2016 by gutsandgrowth

Briefly noted: JA Leon et al. Gastroenterol 2015; 149: 1697-99. Case report of Job syndrome (Autosomal-Dominant Hyper-IgE syndrome) mimicking Crohn’s disease in a 37 yo with perianal fistula, and weight loss. Clues to the diagnosis: “Recurrent skin abscesses and respiratory infections, eczema, marked elevation of serum IgE, eosinophilia, and mucocutaneous candidiasis are the hallmark of the infectious and immunologic features…Boils and furuncles almost always occur and characteristically lack of the usual inflammatory findings…”cold” abscesses…associated with markedly increase IgE or eosinophil levels, should always raise a suspicion for AD-HIES.”

Related blog post: Add it to the list | gutsandgrowth

The Push to Improve Diagnosis

Posted on January 9, 2016 by gutsandgrowth

The Institute of Medicine’s (now called the National Academy of Medicine) “Improving Diagnosis in Health Care” (the link includes a link to a 1-hour briefing) is receiving a lot of attention. One recent commentary (H Singh, ML Graber. NEJM 2015; 373: 2493-95) elaborates on this issue. The IOM reports notes that “diagnostic errors affect at least 1 in 20 U.S. adults in outpatient settings each year, or 12 million adults per year.”

The report recommends “strengthening teamwork, reforming the teaching of diagnosis, ensuring that health information technology (IT) supports the diagnostic process, measuring and learning from errors in real-world practice, promoting a culture of diagnostic safety, reforming the malpractice and reimbursement systems, and increasing research funding.”

My take: This report highlights an enormous challenge for the healthcare system. While IT support in theory sounds like it could help, right now IT isn’t helping much. Many physicians are bogged down inputting data and trying to find enough time for critical thinking. There is a lot of work ahead.

Burden of GI Diseases in U.S.

Posted on January 8, 2016 by gutsandgrowth

A useful article (AF Peery et al. Gastroenterol 2015; 149: 1731-41) provides data on the huge impact that GI & Liver diseases have.

Here are some key findings:

Leading GI symptoms (Ambulatory visits) in 2010 (Table 1):

Abdominal pain 27.1 million
Diarrhea 5.6 million
Vomiting 5.5 million
Nausea 4.7 million
Bleeding 3.6 million

Most Common Diagnosis from Hospital Admissions in 2012 (Table 5):

GI hemorrhage 507,440 admissions
Cholelithiasis with cholecystitis 389,180 admissions
Acute pancreatitis 275,170 admissions
Intestinal obstruction 256,775 admissions
Appendicitis 248,080 admissions
Chronic liver disease/viral hepatitis 243,170 admissions

Causes of Death in U.S. in 2012 (Table 7):

Colorectal cancer 51,139
Pancreatic cancer 38,797
Liver/bile duct cancer 22,973
Cirrhosis 17,495
Alcoholic liver disease 17,419

Gastroenterology Cover

Should Methotrexate Be Used For Ulcerative Colitis?

Posted on January 7, 2016 by gutsandgrowth

A recent study (F Carbonnel et al. Gastroenterol http://dx.doi.org/10.1053/j.gastro.2015.10.050, article in press; thanks to KT Park twitter feed for reference) with 111 patients provides more questions than answers. It appears that methotrexate improved clinical remission but the overall difference is fairly small; the abstract is below.

My initial impression: Immunomodulators (including methotrexate and thiopurines) have some efficacy as monotherapy agents in patients with inflammatory bowel disease. Their role as part of combination therapy (with anti-TNF agents) has been associated with improved outcomes but how long to use combination therapy and at what dosage is still being worked out.

Here’s the abstract and a link: Methotrexate is not Superior to Placebo in Inducing Steroid-free Remission, but Induces Steroid-free Clinical Remission in a Larger Proportion of Patients with Ulcerative Colitis

Background & Aims

Parenteral methotrexate is an effective treatment for patients with Crohn’s disease but has never been adequately evaluated in patients with ulcerative colitis (UC). We conducted a randomized controlled trial to determine its safety and efficacy in patients with steroid-dependent UC.

Methods

We performed a double-blind, placebo-controlled trial to evaluate the efficacy of parenteral methotrexate (25 mg/week) in 111 patients with corticosteroid-dependent UC at 26 medical centers in Europe, from 2007 through 2013. Patients were given prednisone (10 to 40 mg/day) when the study began, and randomly assigned to groups (1:1) given placebo or methotrexate (intramuscularly or subcutaneously, 25 mg weekly) for 24 weeks. The primary endpoint was steroid-free remission (defined as a Mayo score ≤ 2 with no item > 1 and complete withdrawal of steroids) at week 16. Secondary endpoints included clinical remission (defined as a Mayo clinical subscore ≤ 2 with no item > 1) and endoscopic healing without steroids at weeks 16 and/or 24, remission without steroids at week 24, and remission at both weeks 16 and 24.

Results

Steroid-free remission at week 16 was achieved by 19/60 patients given methotrexate (31.7%) and 10/51 patients given placebo (19.6%)—a difference of 12.1% (95% confidence interval [CI], –4.0% to 28.1%; P=.15). The proportions of patients in steroid-free clinical remission at week 16 were 41.7% in the methotrexate group and 23.5% in the placebo group, for a difference of 18.1% (95% CI, 1.1%–35.2%; P=.04). The proportions of patients with steroid-free endoscopic healing at week 16 were 35% in the methotrexate group and 25.5% in the placebo group—a difference of 9.5% (95% CI, –7.5% to 26.5%; P=.28). No differences were observed in other secondary endpoints. More patients receiving placebo discontinued the study because of adverse events (47.1%), mostly caused by UC, than patients receiving methotrexate (26.7%; P=.03). A higher proportion of patients in the methotrexate group had nausea and vomiting (21.7%) than in the placebo group (3.9%; P=.006).

Conclusions

In a randomized controlled trial, parenteral methotrexate was not superior to placebo for induction of steroid-free remission in patients with UC. However, methotrexate induced clinical remission without steroids in a significantly larger percentage of patients, resulting in fewer withdrawals from therapy due to active UC.

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Banning Mills

Optimism for New Treatment in Inflammatory Bowel Disease: AJM300

Posted on January 6, 2016 by gutsandgrowth

Yesterday’s post on “Eternal Nutrition” had a link to podcasts on enteral nutrition as therapy for Crohn’s disease. I listened to the podcasts and they were helpful (Enteral Therapy as Primary Therapy for Crohn’s Disease Podcast). A few points that were made included the following:

Try to have the right person teach/place the nasogastric feeding tube. If the first experience is bad, this may make further attempts quite difficult. At CHOP, their facility has an education center and they schedule 3-hour learning session for enteral feeds. Teaching the teen to place the NG tube is preferred.
Many pediatric gastroenterologists in U.S. are not informing their patients that enteral feedings are a treatment option.
In most parts of the world, induction with enteral nutrition involves virtually 100% of diet as enteral nutrition for ~8-12 weeks. CHOP modification involves 80-90% of calories delivered enterally, typically over an overnight drip. If someone is not responding to enteral feeds, CHOP may increase calories delivered enterally.
For maintenance with CHOP modification, gradually reduction from 7 days per week to 5 days per week is attempted. At CHOP, they prefer hydrolysate for enteral tube feedings and think more rapid gastric emptying could be helpful. However, the podcast state that specific formulas have not been shown to be superior in trials to date. At CHOP, if formula is taken orally, then an intact protein formula is selected.
If someone uses enteral formula for maintenance, then consideration of a gastrostomy tube (after 3 months) is reasonable. They have not had local issues at sites due to Crohn’s disease.
Resources include the Oley.org website and the Crohn’s Survival Guide.
Enteral therapy seems to work in small bowel as well as colonic disease, despite early reports suggesting less efficacy with colonic disease.

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A recent phase II study (N Yoshimura et al. Gastroenterol 2015; 149: 1775-83) indicates that an oral antagonist of α4 integrin may be quite useful for ulcerative colitis.

This double-blind, placebo-controlled trial with 102 patients found the following:

A clinical response rate at 8 weeks of 62.7% in the treatment group and 25.5% for placebo)
Rates of remission were 23.5% in the treatment group compared with 3.9% in the placebo group.
Mucosal healing were 58.8%% in the treatment group compared with 29.4% in the placebo group.
No serious adverse events were noted.

In the commentary by BG Levesque and S Ghosh (pg 1669-72), it is noted that subsequent oral integrins will be compared to vedolizumab and similar safety concerns exist; that is making sure that there are no cases of progressive multifocal leukoencephalopathy (PML) which has been associated with natalizumab therapy. For vedolizumab, the RAMP safety monitoring program has NOT identified PML in 2884 IBD patients.

The commentary (in blue) discusses several integrins as potential therapeutic targets and outlines future therapies.

Nontargeted therapies:

A) Induction: corticosteroids, 5- aminosalicylates, cyclosporin, and tacrolimus
B) Maintenance: thiopurines, methotrexate, 5-aminosalicylates, and tacrolimus.

Targeted therapies (those in development phase in italics)

A) Monoclonal antibodies (induction and maintenance): tumor necrosis factor inhibitors, vedolizumab, other integrin/adhesion molecule inhibitors, interleukin-12/23 inhibitors, and interleukin-6 inhibitors.
B) Oral synthetic (induction and maintenance or stop and start): Jakinibs, integrin blockers, sphingosine-1-phosphate (s1P) regulators, and SMAD7 antisense oligonucleotide.

“The results of AJM300 demonstrate feasibility of such an approach, and we anticipate a proliferation of such approaches given the robust evidence supporting integrins as a target, especially if the drug can be targeted or delivered in a gut-specific manner.”

My take: There are a number of therapies being developed that are likely to transform the treatment of inflammatory bowel disease; future treatments will be more precise, more effective and have many more options.

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Banning Mills

“Eternal Nutrition” Therapy

Posted on January 5, 2016 by gutsandgrowth

NASPGHAN twitter feed (with links to enteral therapy podcasts) was probably a typo &/or autocorrect issue:

“Podcast series must! Eternal Nutrition as Primary Therapy for Crohn’s disease. #nutrition #crohns #podcast ow.ly/WB7Y9”

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