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.

Checklists for Crisis and Daily Care

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Not surprisingly, a new study has shown that checklists were associated with improvement in the management of operating-room crisis (NEJM 2013;  368: 246-53).

Many people use a checklist just to go to the grocery store so they don’t forget something important.  In medicine, checklists offer the same opportunity.

In this particular study, 17 operating-room teams participated in 106 simulated surgical crisis scenarios.  When checklists were available, there was better adherence to lifesaving processes: only 6% of steps were missed with checklists compared with 23% when they were unavailable.  Every team performed better when the crisis checklists were available.  Furthermore, 97% of participants reported they would prefer to have a checklist in the event of a crisis.

There were many limitations of this study, particularly the absence of surgeons from most of the simulations (due to difficulty enlisting them as volunteers).  Nevertheless, “experts have long recognized the potential for human fallibility in complex systems…it has been nearly 100 years since the surgeon W. Wayne Babcock called for emergency protocols to be rehearsed and ‘posted on the walls of every operating room.'”

For a pediatric gastroenterologist, the implication of this study is much broader.  It is trying to develop a checklist for every patient.  For a patient with a GI bleed, that checklist may include a supply list for the endoscopy suite, having written instructions for the settings of the cautery equipment, checking the proper PPI dose, and drawing a specific set of labs.  Agreeing to a minimum and not-too-onerous checklist would be worthwhile for almost anybody.  If you have a checklist for any GI condition (or a mobile app), think about adding a comment to this posting. If something is important in day-to-day care of a specific condition, a “hardstop” can be incorporated into electronic records as a reminder.

Related blog entries (mostly guidelines –not really checklists for a few specific conditions):

A much more articulate spokesman for checklists would be Atul Gawande:

Limiting Cow’s Milk for EoE

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A small retrospective study suggests that eliminating cow’s milk, without other interventions, can be effective in the treatment of Eosinophilic Esophagitis (EoE) (JPGN 2012; 55: 711-16).

Out of 161 children with EoE, 17 patients were identified who excluded only cow’s milk from their diet.  Remission was noted in 65%.  Complete histologic remission (≤1 eosinophil/hpf) was noted in 7 patients (41%) and 4 (24%) had “significant remission” (defined as peak eosinophil count of 2-15/hpf).

This study, conducted in Chicago, took place between 2006-2011.  The majority of the patients treated at this institution are treated with dietary elimination: 61% with empiric elimination diet, 8% empiric elimination diet with topical steroids, and 7% with elemental diet.

The authors suggested that younger children may be more likely to benefit from this approach but cautioned against drawing firm conclusions due to the small ‘scope’ of this retrospective study.

 Related posts:

T-cell therapy for Crohn’s disease

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Data from the Crohn’s and Treg Cells Study (CATS1) are very preliminary but indicate that administration of antigen-specific T-regulatory cells (Tregs) to refractory Crohn’s disease (CD) patients could be effective (Gastroenterol 2012; 143: 1207-17).  Tregs are specialized subpopulations of T-cells.

In this study, the investigators, performed a 12-week open-label multicenter single injections study of 20 patients with refractory CD.  After withdrawing blood from patients, mononuclear cells were isolated and cultured.  Subsequently, T cells were cloned.  A specific subset with high IL-10/IL-13 production and low IL-4 production were selected.

Key findings:

  • 8 of 20 (40%) patients had a CDAI reponse at 5 and 8 weeks.  This was associated with a reduction in serum CRP and a trend of decreasing fecal calprotectin.
  • Remission was noted in 3 patients at week 5 and in 2 patients at week 8.
  • Overall, regardless of dose used, the safety profile was “in line” with severe active refractory CD.  Gastrointestinal adverse events were common.  7 patients had CD flares. One patient died due to suicide.

To understand this study more fully, an accompanying editorial is in the same issue (pages 1135-38).  A more complete discussion of the function of Treg cells is given, included their physiologic role of patrolling the gut lamina propia for antigens ‘derived from food and commensal flora.’  Circulating Treg cells may be deficient in IBD patients and thus contribute to the pathogenesis.

While injecting Treg cells may become a useful therapy, other ways of boosting Treg cells may be enhanced as an alternative.  Currently, granulocyte colony-stimulating factor (GCSF), anti-TNFα agents, and IL-2 all have the potential to enhance Treg cell function.  This supports the editorial’s conclusion that ‘Treg cells are rapidly moving from the bench to the bedside.’

Given the experimentation with stem cell therapy and bone marrow transplantation for CD, Treg cells show promise of a much more targeted effect on the immune system.

Additional references:

  • -Blood 2010; 116:6123-32.  Autologus stem cell transplantation in patients with refractory CD.
  • -Gut 2008; 57: 211-17.  Autologus stem cell transplantation for refractory CD.
  • -Gut 2010; 59: 1662-69.  Mesenchymal stromal cell treatment for luminal Crohn’s.

Could Cysteamine help NAFLD?

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Maybe (J Pediatr 2012; 161: 639-45, editorial p 579).

Cysteamine bitartrate has been used in cystinosis and reduces intralysosomal Cys accumulation.  It has potential antioxidant and antiapoptotic effects.  A pilot study has shown that cysteamine may improve NAFLD through unclear mechanisms and may reduce aminotransferase levels in the serum along with increasing adiponectin levels (reduced in NAFLD).

Adiponectin is produced by adipocytes and helps regulate glucose and lipid homeostasis.  It has insulin-sensitizing properties as well as anti-inflammatory effects. Adiponectin levels inversely correlate with degree of obesity and insulin resistance.

In this study of 10 children with biopsy-proven NAFLD, cysteamine therapy was administered for 24 weeks.

  • Following therapy, multimers of adiponectin were increased and total adiponectin level increased 49.3% (P = 0.05).
  • ALT dropped from a mean of 123 IU/L at baseline to 55 IU/L at 24 weeks.
  • AST dropped from a mean of 61 IU/L at baseline to 32 IU/L at 24 weeks.
  • Adiponectin values returned to baseline 16 weeks after completing treatment while aminotransferase values remained low.

The editorial notes that an NIH-funded NASH clinical research network study will investigate cysteamine in a much larger cohort.

Related blog entries:

Challenging the Obesity Myths

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A recent provocative article highlights the myriad misconceptions regarding obesity (NEJM 2013; 368: 446-54).

According to the authors, many of the obesity recommendations are fallacies:

  • Myth: “Small sustained changes in energy intake will produce large long-term weight changes.” Fact: Because of changes in body mass, the energy requirements change which results in only modest improvement.
  • Myth: “Setting realistic goals for weight loss is important.” Fact: Setting realistic goals has not been shown to improve outcomes over more ambitious goals.
  • Myth: “Rapid weight loss is associated with poorer long-term weight-loss outcomes, as compared with slow, gradual weight loss.”  Fact: Ultimate success in terms of body weight is better with greater initial weight loss.
  • Myth: “It is important to assess…diet readiness.” Fact: Readiness does not predict the magnitude of weight loss or treatment adherence among those who sign up for behavioral programs or undergo weight loss surgery.
  • Myth: “Physical-education classes…play an important role in reducing or preventing childhood obesity.” Fact: Physical education, as typically provided, has not been shown to reduce or prevent obesity.
  • Myth: “Breast-feeding is protective against obesity.” Fact: “Studies with better control for confounding..involving more than 13,000 children who were followed for more than 6 years provided no compelling evidence of an effect of breast-feeding on obesity.”
  • Myth: “Sexual activity burns 100-300 kcal for each participant.” Fact: “Incremental benefit of one bout…is plausibly on the order of 14 kcal.”  (This is going to dampen the all-you-need-to-lose weight is to become a pornography star craze.)

Presumptions -also not proven:

  • Eating breakfast is protective against obesity
  • Early childhood learning regarding exercise and eating influence our weight throughout life
  • Eating more fruits and vegetables will result in weight loss
  • Snacking contributes to weight gain
  • Availability of parks and sidewalks influence the development of obesity

Facts:

  • Reducing energy intake (dieting) can be effective.
  • Increased exercise improves health.
  • Programs that involve parents promote greater weight loss.
  • Some pharmaceutical agents can help.
  • Bariatric surgery can be lifesaving treatment in some cases.
  • Heritability is not destiny.  Moderate sustained environmental changes can be effective.

 

Some related links:

Avoid breastfeeding to lower the risk of HIV

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AAP recommends against breastfeeding infants of HIV-infected mothers:

http://pediatrics.aappublications.org/content/early/2013/01/23/peds.2012-3543.abstract?papetoc

“It is critical that physicians are aware of the HIV transmission risk from human milk and the current recommendations for feeding HIV-exposed infants in the United States. Because the only intervention to completely prevent HIV transmission via human milk is not to breastfeed, in the United States, where clean water and affordable replacement feeding are available, the American Academy of Pediatrics recommends that HIV-infected mothers not breastfeed their infants, regardless of maternal viral load and antiretroviral therapy.”

Thanks to Mike Hart for sharing this link.

Antibiotic resistance: doomed to repeat

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“We’re doomed to repeat the past no matter what. That’s what it is to be alive. It’s pretty dense kids who haven’t figured that out by the time they’re ten.” Kurt Vonnegut, Bluebeard

“Those who don’t know history are destined to repeat it.” Edmund Burke

Antibiotic resistance has been occurring for billions of years and will keep on happening (NEJM 2013; 368: 299-301).  This commentary offers a different perspective and indicates that Kurt Vonnegut’s quote is more appropriate for this post.  Some key points:

  • “We live in a bacterial world where we will never be able to stay ahead of the mutation curve.” We will run out of targets to attack microbes.
  • Bacteria “invented” antibiotics billions of years ago, and “resistance is primarily the result of bacterial adaptation to eons of antibiotic exposure.” Thus, even with good antimicrobial stewardship, resistance will still occur.
  • Antibiotic resistance has been identified in bacteria found in underground caves that have been geologically isolated from the planet surface for four million years.
  • In 1945, Alexander Fleming called for stopping the overuse of penicillin to slow the development of resistance.
  • In 2009, three million kilograms of antibiotics were administered to humans and 13 million kilograms to animals.

Possible useful steps: more vaccines to prevent infections, smaller antibiotic clinical trials, use of rapid biomarkers to withhold antibiotics from those without bacterial infections, stopping antibiotics to help livestock growth, better waste-treatment of antibiotics, ‘self-cleaning’ hospital rooms, and better drug delivery to avoid foreign materials in intensive care patients.

Related blog entry:

Green beans for short gut syndrome

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A recent article indicates that the addition of green beans may improve diarrhea and reduce dependence on parenteral nutrition (Adding Dietary Green Beans to Formula Resolves the Diarrhea …) (ICAN. DOI: 10.1177/1941406412469403). Thanks to Kipp Ellsworth for pointing out this reference on his twitter feed.

This small retrospective study of 18 infants examined the addition of green beans to the diet of infants with short bowel syndrome (SBS) (1 jar of stage 2 baby food green beans to every 8 ounces of 30 cal formula).  The average gestational age of the patients was 32 weeks (range 23-39 weeks) and the average birth weight was 1938 gram.  Nine patients had NEC, four had gastroschisis, two had Christmas tree defect, and three had other reasons for either SBS or intestinal failure.  The IF group (n=10) was defined as being dependent on parenteral nutrition to meet nutritional needs; the SBS group (n=8), who were more severely affected, was defined as the malabsorptive state that follows a massive resection.

Products that were used:

  • Gerber Natural Select: 3 gm of fiber per 4 ounce
  • Beach-Nut Homestyle: 2 gm of fiber per 4 ounce
  • HyVee Mother Choice: 2 gm of fiber per 4 ounce
  • These products average 32% soluble and 68% insoluble fiber

While the authors note that they use only amino-acid based formulas currently, at the time of the study, 61% were receiving Peptamen Junior.

It is not clear in the manuscript exactly at what age green beans are introduced. However, a previous case study suggested addition of green beans at ~4 months or >44 weeks postconception.  This prior case study indicated that adding stage 2 green beans changed the caloric density of 30 cal formula to 22 cal/ounce (Nutrition in Clinical Practice 2005; 20: 674-77).  In addition, this adds 2 gm/kg/day of fiber.

Results from current study:

  • 9 of 10 IF patients were able to discontinue parenteral nutrition
  • 2 of 8 SBS patients were able to discontinue parenteral nutrition
  • All infants had improvements in stool consistency, typically within 24 hours of dietary change.

While the authors acknowledge the limitations of the study, they hypothesize that the reason for improvement is due to the fiber content of green beans.   Fermentation of dietary fiber produces short chain fatty acids (SCFAs) which in turn have a trophic effect on the mucosa and enhance nutrient absorption.

Studies have shown that adults with IF or SBS have improved stool consistency with the addition of fiber.  However, the authors note that there have been no studies documenting the effectiveness of dietary fiber in the pediatric SBS/IF population.

Whether green beans would outperform other sources of fiber like pectin, guar gum, bananas or benefiber is not clear.

Additional references/links:

Feeling the urge and stopping the shame

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So many parents misinterpret withholding behavior in children.  Many indicate that their child is trying to go but cannot and others indicate that their child does not feel an urge to defecate.  Now more insight into this common issue has emerged (JPGN 2013; 56: 19-22).

The authors reviewed their experience with colonic manometry (n=410).  150 patients were identifed as having functional constipation.  Among this group, 56 patients volunteered that they had no urge to defecate.

Yet, during colonic manometry, when the first high-amplitude propagating colonic contraction (HAPC) occurred, this was associated with retentive posturing, grimacing or denial of sensation.  When the HAPC occurred, the examiner would explain that it was causing pain that would improve if the child defecated.  Ultimately, “every patient acknowledged an urge to defecate and successfully defecated.”

One other interesting part of this publication is the discussion of psychological aspects.  Do you remember Erikson’s stages (Erik Erikson – Wikipedia, the free encyclopedia)?  The authors note, “if toilet training is not achieved or the process involves negative experiences including being shamed into the process, shame and doubt will persist.  Shame, according to Erikson, is an infantile emotion and leads to secretive behavior.  Therefore, children who failed toilet learning may deny sensations of the urge to defecate…all the while having shame and embarrassment.”

These psychological issues are important in the propagation of constipation. The authors note that, even in children with rectal distention due to chronic constipation which could result in decreased sensation, studies have shown rectal compliance was not associated with treatment failure.  Therefore, constipation and soiling are not simply due to a mechanical issue of not knowing when to go.

Related posts:

Colic Microbiome

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A new study identifies a potential microbiome signature that is associated with colic (Pediatrics 2013; 131: e550-58). Thanks to Mike Hart for this reference.

With new technology, the microbiome’s role in many gastrointestinal conditions is being unraveled.  For colic, there has been concern about that an abnormal microbiome has been contributing to the pathophysiology.  On a personal level, I have had an interest in this subject for quite a while:

In this current study, the authors serially followed the microbiome infants in a prospective longitudinal project.  Nine stool specimens were obtained from each infant. Four were obtained in the first month at day of life 2, 7, 14, and 28 days.  Five were obtained at 3 to 5 months.  All specimens were stored at -20°C until analyzed by the “Human Intestinal Tract Chip (HITChip).” The HITChip microarray was considered satisfactory if 2 independent hybridizations had >95% correlation.  These microarrays “showed a dynamic range of >10,000-fold and >200 independent microarray readouts were used.”

Of 160 healthy term infants, the authors identified colic in 25% who averaged >180 minutes of crying per day over a four-day period.  Then, the authors selected the 12 infants who cried the most and compared them to the 12 infants who cried the least.

Results:

  • In the infants who were highly similar, the “infants with colic showed a significantly reduced microbiota diversity at 14 and 28 days of life.”  Proteobacteria, including Enterobacter aerogenes, Escherichia coli, and Klebsiella pneumoniae, were increased with more than a doubled abundance.  Bifidobacteria and lactobacilli were decreased in colicy infants.
  • At about 3-4 months of age, the colic group had a similar microbiome as the non-colicy group.
  • The authors speculate that proteobacteria might cause inflammation and may displace helpful bacteria.  Certain butyrate-producing bacteria like Butyrivibrio crossotus and Coprococcus estates were more commonly present in the non-colicy group.  The authors note that butyrate reduces the pain sensation in adults.

Bottom-line:

These results could explain why administration of probiotics (and possibly antibiotics) can result in a decrease in colic symptoms.

Related blog entries:

Additional references:

  • -Pediatrics 2010; 126: e526.  Double-blind randomized placebo-controlled trial of Lactobacillus reuteri.
  • -J Pediatr 2009; 155:823. Increased calprotectin in colicy infants. n=36. editorial pg 772.
  • -J Pediatr 2009; 154: 514-20. Colic and reflux. (Orenstein et al), & 475 (editorial -Putnam). PPIs (lansoprazole) do not help colicy Sx in infants c GERD. n=162. Increased resp infections in pts on PPIs. 44% response in Rx & control group.
  • -J Pediatr 2008; 152: 801. Probiotic helped reduce colic sx in 30 preterm infants, Lactobacillus reuteri
  • -Pediatrics 2007; 119; e124. Probiotics reduced colic in breastfed babies more than simethicone. n=83, lactobacillus reuteri, 10-8th power per day. Decreased crying 18 minutes per day at 1 week compared to simethicone & by 94 minutes/day at 4 weeks (95% response vs 7% of simethicone)
  • -Pediatrics 2005; 116: e709. Low-allergen maternal diet was helpful.
  • -Arch Pediatr Adol Med 2002; 1183 &1172. lack of sequelae on maternal mental health.
  • -Arch Pediatr Adol Med 2002; 156: 1123-1128. colic 24% of infants, breastfeeding did not help.
  • -Pediatrics 2002; 109: 797-805. carbohydrate malabsorption with breath testing in colicy infants, n=30. 2 hour fasting period.
  • -Arch Dis Child 2001; 84: 138-41. Lack of benefit (vs placebo) of chiropractic manipulation for colic, n=100. 86 completed study. 70% improved vs 60% in placebo.
  • -JPGN 2001; 33:110-111. Lack of assoc c GER
  • -Pediatrics 2000; 106: 1349. Use of hydrolysate decreased crying by 63mins/day
  • -Pediatrics 2001; 108; 878-882. No assoc between colic and markers of atopy/asthma/allergy.