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.

Fructose Restriction Improved Fatty Liver Disease in Children

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A recent study (J-M Schwarz et al. Gastroenterol 2017; 153: 743-52, editorial MB Vos, IR Goran Gastroenterol 2017; 153: 642-5 ) showed that restriction of fructose quickly improved fatty liver disease.

Several points from the editorial:

  • “The metabolic driver of buildup of fat storage in the liver is de novo lipogenesis (DNL) and fructose is a major substrate of DNL”
  • “In the healthy state, DNL is not expected to be a major contributor to lipid accumulation in the liver….[but] in a fatty liver, it has been estimated that 26% of the fat originates from DNL.”
  • Fructose is “limited in a natural diet…However, it is added to many processed foods and drinks in the form of cane sugar..and other types of sugars, going by ≥57 different names.”
  • Fructose is “commonly used in animal models to induce hepatic steatosis.”

The study is summarized in a recent AGA Journals Blog: Can Restricting Fructose Intake Reduce Fatty Liver Disease in Children?

An excerpt:

Jean-Marc Schwarz et al performed a clinical trial to investigate the effects of reducing fructose intake for 9 days in obese Latino and African American children with habitual high sugar consumption (fructose intake >50 g/day). They measured the effects of isocaloric fructose restriction on de novo lipogenesis, liver fat, visceral fat, subcutaneous fat, and insulin kinetics.

In their study, 41 children, 9−18 years old, had all meals provided for 9 days. The meals had the same energy and macronutrient composition as their standard diet, but with starch substituted for sugar, yielding a final fructose content of 4% of total kilocalories. The authors measured metabolic factors before and after fructose restriction. They measured liver fat, visceral fat, and subcutaneous fat by magnetic resonance spectroscopy and imaging.

Schwarz et al found that on day 10 of the diet, liver fat decreased from a median 7.2% at baseline to 3.8%, and visceral fat decreased from 123 cm3  at baseline to 110 cm3. Liver fat decreased in all but 1 of the 38 participants for whom paired data were available…

De novo lipogenesis decreased significantly after 9 days of fructose restriction; the de novo lipogenesis area under the curve value on day 10 decreased from 68% at baseline to 26% after the diet, in childen with low or high baseline levels of liver fat.

Insulin secretion during fasting and in response to an oral glucose tolerance test decreased significantly in children with low and high baseline levels of liver fat…

In an editorial that accompanies the article, Miriam B. Vos and Michael I. Goran say that it will be important to determine whether the effects of fructose reduction are sustained past 9 days…Vos and Goran state that it is important for physicians, nutritionists, schools, and parents to find ways to reduce fructose in the diets of children and patients with NAFLD.

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Early Results with Upadacitinib -a JAK1 Inhibitor for Crohn’s Disease

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From Gastroenterology & Endoscopy News: New JAK1 Inhibitor Treats Most Challenging Crohn’s Patients

An excerpt:

An experimental oral JAK1 inhibitor, upadacitinib (AbbVie), has been tested in the most clinically challenging patients with Crohn’s and yielded impressive results. The drug led to a clinical response in 61% of these patients and remission in 22%, the new data show…

William Sandborn, MD, chief of gastroenterology at the University of California, San Diego, who led the study. “It seems to be a really effective drug in a very difficult-to-treat patient population, and the oral route of administration is attractive.”

Dr. Sandborn’s group presented the findings at the 2017 Digestive Disease Week (abstract 974h).

The CELEST trial enrolled 220 patients with active, moderate to severe Crohn’s disease. Patients received 16 weeks of induction therapy with one of five dosing regimens of upadacitinib or a placebo…

Dr. Sandborn called the findings particularly impressive given that the study participants are the most refractory patient population ever recruited in a trial for Crohn’s disease. “And this is also one of the first trials to meet new FDA requirements for demonstrating clinical remission using patient-reported outcomes as well as endoscopic improvement,” he noted.

My take: It is exciting that another oral agent may be helpful. Tofacitinib, a different JAK1 inhibitor, has data supporting its use in ulcerative colitis but not with Crohn’s disease.

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Rarely Seen and “Do Not Miss” Explanation for Failure to Thrive

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A fascinating case report (MA Curran et al. NEJM 2017; 377: 1468-77) provides a useful exercise in understanding how to evaluate difficult cases of “failure to thrive.”

From NEJM twitter feed

In essence, a 19 month girl with good linear growth had stopped gaining weight around 7 months of age.  After exhaustive evaluation, detailed in this report, the patient had an MRI which revealed a brain tumor and she was diagnosed with diencephalic syndrome. Key features include good appetite/caloric intake, happy appearance, and cachexia.

The discussion explains that in most children, poor weight gain results from poor caloric intake, which can be related to social issues including poverty, neglect, parental mental health issues, and lack of understanding by caregivers.

In children with good caloric intake, the potential reasons for poor growth are reviewed:

  • Endocrine causes: thyroid dysfunction
  • Renal, pulmonary, cardiac, liver, and pancreatic disease
  • GI diseases: Celiac disease, Inflammatory Bowel disease
  • Infections including tuberculosis, parasites, HIV

Despite the numerous potential causes, beyond basic laboratory assessment,  “extensive testing is usually not warranted: in one study, only 1.4% of additional laboratory tests were helpful in making the diagnosis.”

In many cases of diencephalic syndrome, symptoms like vomiting may be present on an intermittent basis as well as nystagmus or strabismus; these symptoms develop due to obstructive hydrocephalus.

My take: In children with good caloric intake, diencephalic syndrome is a rare but important etiology.

 

 

ACG World Congress -Useful Tweets

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I wanted to share several tweets from this year’s ACG World Congress that looked helpful.

Topic: SBBO and IBS-D

A positive breath test is the ONLY variable that can predict response to Rifaximin in IBS-D: ACG and Mark Pimenthal. tweet from @AllRezale, MD

Topic: Polyps -slides recommend cold forceps for polyps 1-3 mm and cold snare for 4-5  mm polyps.

Topic: Hereditary Colorectal Cancer Syndromes

Topic: Aggressive fluids for pancreatitis

Rising BUN is Associated with mortality with pancreatitis. Tauseef, Ali @ibdtweets: “Pancreatitis pearls: aggressive fluid hydration 250-500 cc lactated ringer’s (my personal favorite also) and ensure BUN dropping #WCOGatACG2017”

Expert 2017 Opinion: Miralax is (Still) First Choice Laxative for Children

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IJN Koppen et al. Journal of Pediatric Gastroenterology & Nutrition: October 2017 – Volume 65 – Issue 4 – p 361–363

Abstract:

 According to international guidelines, polyethylene glycol (PEG) is the laxative of first choice in the treatment of functional constipation in children, both for disimpaction and for maintenance treatment. PEG acts as an osmotic laxative and its efficacy is dose dependent. PEG is highly effective, has a good safety profile, and is well tolerated by children. Only minor adverse events have been reported. Overall the use of PEG in children has been reported to be safe, although in patients predisposed to water and electrolyte imbalances monitoring of serum electrolytes should be considered.

Because this topic is of great importance to the families that are seen by pediatric gastroenterologists (and pediatricians), I wanted to review this brief article which describes the efficacy and safety of polyethylene glycol (aka miralax).

Key Points:

  • Polyethylene glycol (PEG) is the most widely used laxative in children and adults
  • It works by interacting “with water molecules by forming hydrogen bonds, in a ratio of 100 water molecules per 1 PEG molecule, which leads to an additional increase in colonic water content.” It is minimally absorbed.
  • Studies have demonstrated that PEG is better or noninferior to all of the following: lactulose, milk of magnesia, mineral oil, and flixweed (a medicinal herb)

Safety:

  • Only minor adverse events have been reported in studies.  In randomized, placebo-controlled trials, adverse events “did not occur more frequently in patients receiving PEG compared to patients receiving placebo.”
  • The main safety issue has been when it has been administered via nasogastric administration; improper placement can lead to severe pulmonary complications.  In addition, PEG should be used “cautiously in children with swallowing problems…because of risk of aspiration.”

Combatting Myths: 

  • The authors assert that there has never been reports of physical or psychological dependence.  Weaning from PEG is to prevent relapse of constipation.
  • There is no evidence to support loss of efficacy.
  • The phenomenon of “lazy bowel syndrome” in which there is worsened colonic function has not been described due to PEG; though, patients with underlying motility problems have had these problems misattributed to PEG use.
  • Despite anecdotal reports of tremors, tics, and obsessive-compulsive behavior in children taking PEG, there has been no evidence of a causal relationship.  “These events …are still under investigation, but the FDA has decided that no action is necessary.”  The authors note that the co-occurrence of neuro-behavioral problems and constipation is well-recognized in children with and without laxative use.

Clinical Pearl: Stimulant Laxatives After Repaired Anorectal Malformations:

  • “In children with constipation after repaired anorectal malformations, …stimulant laxatives (eg. senna) should be the laxative of choice.” (J Pediatr Surg 2017; 52: 84-8)

My take (borrowed from the authors): “PEG has rapidly become the treatment of first choice for children with functional constipation.”

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Too Much Zinc

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An interesting case report (DL Saly et al. NEJM 2017; 377: 1379-85) describes a 61 year old woman with multiple medical problems who developed numbness and tingling in hands/feed which progressed to unsteady gait and inability to stand.

Her medical problems included end-stage renal disease requiring dialysis, COPD, hepatitis C, depression,reflux, breast cancer, hypertension, and chronic back pain. Due to dysgeusia and suspected zinc deficiency associated with dialysis, she had been started on zinc therapy and this was doubled when she did not improve.

Ultimately she was diagnosed with copper deficiency which can result from zinc toxicity, “because zinc upregulates the protein to which copper binds in enterocytes, and an excess of zinc forces copper to be trapped in the enterocyte and unavailable for absorption.”

My take: Too much zinc (as well as other micronutrients/vitamins) can result in adverse effects.

Related blog posts:

 

FDA Postapproval Studies: ‘You can have pie as long as you do your homework later’

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A recent commentary (S Woloshin et al. NEJM 2017; 377: 1114-7) examines the fate of FDA postapproval studies.

“Both Congress and the Food and Drug Administration (FDA) have sought to accelerate the “availability of new drugs by allowing sponsors to wait to resolve many questions about safety and benefit until after their drugs receive marketing approval.”

However, this commentary points out that many times these studies are never completed. The authors examined these studies since 2009.  Key finding:

  • “After 5 to 6 years, 20% of postapproval studies had not been started, 25% were delayed or ongoing, and 54% had been completed.”

The authors note ‘the slow irregular pace of postapproval studies contrasts starkly with the short, rigid deadlines and other shortcuts used to speed marketing approval.”  They suggest that the FDA impose fines and establish shorter deadlines.  They indicate that the current administrations stated view that the FDA is ‘slow and burdensome’ could necessitate even more reliance on postapproval studies by loosening the evidence for new medication approvals.

In the same issue, the FDA responds that there have been improvements and that since 2015, “88% of postmarketing requirements overall…were progressing according to their original schedules.”

My take: More rapid approvals will inevitably lead to more medications with unrecognized safety signals.  These postapproval studies are crucial in identifying infrequent but important adverse effects.

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America Needs Immigrant (Doctors)

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While anti-immigrant sentiment has become more widespread among many, in medicine it is clear that immigrant physicians play an important role.  This is discussed in a recent NY Times article: Why America Needs Foreign Medical Graduates

The key points:

  1. Foreign medical graduates help fill residency training positions that would otherwise be left vacant.  Their availability helps many hospitals operate.
  2. Foreign medical graduates disproportionately take positions in primary care, accounting for approximately 40% of primary care physicians.
  3. There is evidence that the care of foreign medical graduates is at least as good as physicians who received their medical degrees in the U.S.

An excerpt:

The American system relies to a surprising extent on foreign medical graduates, most of whom are citizens of other countries when they arrive. By any objective standard, the United States trains far too few physicians to care for all the patients who need them. We rank toward the bottom of developed nations with respect to medical graduates per population…

A 2015 study found that almost a quarter of residents across all fields, and more than a third of residents in subspecialist programs, were foreign medical graduates…

 About a quarter of all doctors in the United States are foreign medical graduates.

My take: Physicians from other countries improve the health of our entire country.  In addition, many physicians who train in the U.S. return abroad and help improve health in their home countries.

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How Many Kids with Reflux Actually Have Reflux?

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A terrific recent retrospective study (LB Mahoney, S Nurko, R Rosen. J Pediatr 2017; 189: 86-91) examined how often children with reflux symptoms actually have reflux.

This study reviewed 45 children ≥5 years (mean age 11.8 years) who had undergone both upper endoscopy and impedance pH study (off PPI therapy). Inclusion criteria: no erosive esophagitis. Common symptoms included heartburn, abdominal pain, chest pain, and regurgitation.

Definitions:

  • Nonerosive reflux disease –had abnormal esophageal acid exposure
  • Reflux hypersensitivity -had normal acid exposure but had a positive symptom association to acid or nonacid reflux
  • Functional heartburn -had normal acid exposure and negative symptom association

Key findings:

  • 44% had functional heartburn, 29% with reflux hypersensitivity (27% acid, 2% nonacid), 27% had nonerosive reflux disease (NERD)
  • Response to a proton pump inhibitor (PPI) was not predictive of reflux phenotype: 58% with NERD, 67% with reflux hypersensitivity, and 55% with functional heartburn. Response to PPI was stated as “at least some symptomatic improvement with PPI use.”  There was not a difference in PPI response among those who received a dose <1 mg/kg and those ≥1 mg/kg.
  • Microscopic esophagitis was present in 17% in NERD, 25% with reflux hypersensitivity, and in 20% of functional heartburn

While this study has limitations, including referral bias, it is likely that these patients are typical for many pediatric gastroenterologists. The authors note that typical patients were “patients who underwent a PPI trial but continued to have persistent symptoms.”

My take: In a pediatric gastroenterology setting, the most common reason for “reflux” is actually functional heartburn.  Thus, in those with persistent symptoms, evaluation with endoscopy and pH probe is worthwhile, especially as there has been more attention to potential risks of PPI therapy.

Related blog posts:

View from Asheville, NC

Moving Away from Liver Biopsies

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A recent review (EB Tapper, AS-F Lok. NEJM 2017; 377: 756-68) provides a good review of liver biopsy and liver imaging. My take of this review is that it highlights the emergence of noninvasive tools (imaging & fibrosis markers) which may supplant liver biopsy.  This article does not delve into how more widespread genetic testing may obviate a liver biopsy in many cases as well. The article notes that about 8% of persons in the U.S. have elevated liver enzymes.

Liver biopsy:

  • “A typical liver biopsy samples one fifty-thousandth of the liver.”
  • Limitations of liver biopsy: sampling error is common, biopsy interpretation is subjective, and biopsies can cause complications.  Pain is noted in 30-50% of patients, serious bleeding in 0.6%, injury to other organs (0.08%), and in rare cases, death (up  to 0.1%).
  • Cost: “the average direct cost of a percutaneous liver biopsy is $1448 (in 2016 U.S. dollars).” Transjugular biopsies are much more expensive.  In addition, there are unmeasured indirect costs, due to missing work.

Some prior blogs on liver biopsy

Blood tests:

  • The article details the formulas for biomarker measurements that predict the risk of fibrosis, inlcuding FIB-4, Lok Index, and NAFLD Fibrosis Score.
  • In most liver diseases, aspartate aminotransferase levels “exceed alanine aminotransferase levels when cirrhosis develops.”
  • Thrombocytopenia “is the earliest indicator of cirrhosis among routine blood tests…[due to] diminished liver function (throbopoietin underproduction) and portal hypertension (splenic sequestration).”
  • Proprietary algorithms to assess fibrosis have variable sensitivity, specificity –include FibroTest (aka FibroSure [LabCorp]), FibroMeter, HepaScore (Quest), FIBROSpect, and the Enhanced Liver Fibrosis Score.

Imaging:

  • Elastography with vibration-controlled transient elastography (VCTE) OR magnetic resonance elastography
  • “Elastography offers excellent negative likelihood ratios for advanced fibrosis but much poorer positive likelihood ratios.”
  • Patients with severe obesity are less likely to obtain adequate study with VCTE and could need magnetic resonance elastography to assess fibrosis.

My take: Noninvasive tests have already sharply reduced the need for liver biopsy.

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