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.

Understanding the New Therapies for Spinal Muscular Atrophy

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Pediatric gastroenterologists follow children with spinal muscular atrophy type 1 (Wernig-Hoffman disease) mainly due to feeding problems associated with the profound weakness. Two recent studies show promise for spinal muscular atrophy and are summarized in a “quick take” video: Quick Take NEJM video on SMA type 1

While these new therapies have improved the outcomes, long term data are needed.  With the adenovirus vector gene therapy, if the expression of the gene therapy declines, it may not be possible to do further infusions due to antibody development against the adeonviral vector.

With nusinersen, which has been approved for clinical use, the anticipated cost of $750,000 for the first year of therapy alone and ongoing need for intrathecal administration are problematic.

Incidental Brain Imaging Findings

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A recent study (PR Jansen et al. NEJM 2017; 377: 1593-5) provides some useful insight into the issue of incidental findings with pediatric brain MRIs.  Between 2013-2015, the authors examined 3966 children (mean age 10.1 years) prospectively in an effort to identify influences on development. Key findings:

  • At least one incidental finding was present in 25.6%
  • Most commonly: Pineal gland cysts 16.8% of cohort, Arachnoid cysts 2.17%, Venous anomalies 1.59%, Chiari I malformations 0.63%, subependymal heterotopia 0.48%, partial agenesis of the corpus callosum 0.05%
  • 7 children (0.18%) has suspected primary brain tumors; 2 had neurosurgical treatment
  • Imaging findings requiring clinical followup was only 0.43%

A study CT scans in asymptomatic adults, mean age 63 years, (NEJM 2007; 357: 1821) also found a high incidence of abnormalities, including 7.2% with asymptomatic infarcts, 1.8% with aneurysm, and 1.6% with benign tumors.

My take: The frequency of these incidental findings in the pediatric population is surprising to me.  Having anything reported as abnormal on an MRI is likely very unsettling for parents and often for providers due to uncertainty regarding the significance.

Grand Canyon Sunrise and  then to the South Kaibab Trail (below)

Advice on Arsenic in Baby Foods

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The issue of arsenic, mainly in rice cereal, has been discussed on this blog: Arsenic in Rice –New Recommendations

Renewed widespread publicity on this is likely following a recent NY Times Article: Should You Be Worried About the Arsenic in Your Baby Food?

Here’s an excerpt:

Rice cereal is often a baby’s first solid food, but it contains relatively high amounts of arsenic, a source of growing concern…rice cereals still contain six times more inorganic arsenic, on average, than infant cereals made with other grains like barley or oatmeal.

The new report comes from Healthy Babies Bright Futures, an alliance of scientists, nonprofit groups and private donors that aims to reduce children’s exposures to chemicals that may harm developing brains. One step parents can take immediately to reduce children’s exposure to arsenic is to feed infants cereals made with other grains, the group suggests…

For years, pediatricians have encouraged parents to introduce babies to a wide variety of grains in order to minimize exposure to arsenic…

The Healthy Babies Bright Futures alliance … found that over all, oatmeal, barley, buckwheat, organic quinoa, wheat and rice-free multigrain baby cereals contained much lower amounts of inorganic arsenic than rice cereals..

The average level of arsenic in the rice cereals tested recently was 85 parts per billion, down from an average level of 103 parts per billion found by the F.D.A. when it tested baby cereals in 2013 and 2014…

To reduce your family’s exposure to arsenic, the report suggests choosing a variety of grains including those low in arsenic.

My take: While the levels of arsenic are low, for the infants who are likely more vulnerable, it makes sense to recommend oatmeal cereal rather than rice cereal when introducing solid foods.

 

CFTR Modulators for Cystic Fibrosis

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Two more studies have shown the effectiveness of CFTR modulators for subsets of patients with cystic fibrosis.

  • JL Taylor-Cousar et al. NEJM 2017; 377: 2013-23
  • SM Rowe et al. NEJM 2017; 377: 2024-35.

In the Taylor-Cousar study, the authors treated patients with homozygous Phe508del cystic fibrosis with either combination tezacaftor-ivacaftor or placebo for 24 weeks. Combination therapy resulted in FEV1 that was 4% higher along with a 35% lower rate of pulmonary exacerbations than placebo.

In the Rowe study which examined patients some retained CFTR function (which occurs ~5% of CF patients), a prospective trial of tezacaftor-ivacaftor had a greater effect on increasing FEV1 than ivacaftor alone.  Ivacaftor monotherapy and tezacaftor-ivacaftor combination therapy were both more effective than placebo.

A related editorial (H Grasemann. pgs: 2085-8) helps provide context to help understand the importance of these studies.  His key point:

“Although CFTR modulator therapies have measurable beneficial effects on some aspects of the disease, there is still an unmet need for truly effective new therapies to be developed for all persons with cystic fibrosis.  The clinical efficacy of the current combination therapies for patients with cystic fibrosis who have the most common CFTR genotype (Phe508del/Phe508del) is suboptimal and falls within the range of established symptomatic therapies, such as nebulized inhaled hypertonic saline or recombinant human DNAse.”

This figure depicts the types of molecular defects: No functional CFTR with framshifts for deletions or insertions (class 1), CFTR trafficking defect due to misfolded protein (class II), defective channel regulation (class III), reduced cholirde conductance (class IV) , reduced synthessis (class V) or decreased CFTR stability (class VI)

Projected Obesity Rates: Majority of Today’s Children Will Be Obese in U.S.

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A recent study (ZJ Ward et al. NEJM 2017; 377: 2145-53) pooled observations from 41,567 children and adults.  They extrapolated this data to created 1000 virtual  populations of 1 million children through the age of 19 years.  They performed simulations to predict future obesity levels.

Key findings:

  • Given current levels of childhood obesity the authors predict 57.3% of today’s children will be obese at the age of 35 years.  They defined obesity for adults as BMI ≥35 and for children as 120% or more of the 95th percentile.
  • For children with severe obesity at age 2 years, approximately 80% will be obese at 35 years; whereas approximately 95% of severely obese 19 year olds will be obese at 35 years of age.
  • About half of the total prevalence of obesity at age 35 years begins in childhood in these models.

Because these are simulations, these projections could be influenced by changing circumstances.  Though, the authors note that these projections have corresponded well to measurable trends thus far in NHANES data.

My take: The increasing rates of obesity projected in these models will have profound effects for health but has implications for a wide range of issues: transportation, housing, social, etc.

South Kaibab Trail, Grand Canyon

Nonalcoholic Steatohepatitis Review

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A concise and useful review of nonalcoholic steatohepatitis (NASH): AM Diehl, C Day. NEJM 2017; 377: 2063-72

A couple points:

  • About 25% of adults have fatty livers in the absence of excessive alcohol consumption
  • NASH is strongly associated with obesity/overweight which occur in  >80% of patients
  • NASH comorbidities in adults: 72% with dyslipidemia, 44% with type 2 diabetes mellitus
  • In a typical patient with NASH, liver fibrosis progresses “at a rate of approximately one stage per decade, suggesting that F2 fibrosis will progress to cirrhosis within 20 years.” However, there is considerable variability.
  • It is expected that NASH will be the leading reason for liver transplantation by 2020.
  • Cirrhosis related to NASH increases the risk of hepatocellular carcinoma with this occuring in 1-2% per year of patients with cirrhosis.
  • NASH is estimated to cost >$100 billion currently in annual direct medical costs
  • Staging of NASH and differentiation from isoloated steatosis identifies those at high risk for sequelae.
  • In Table 2, the authors list more than 10 pharmacologic agents in phase 2/3 studies

Current lifestyle treatment recommendations (for adults):

  • Lose 7% of body weight if overweight or obese
  • Limit consumption of fructose-enriched beverages
  • Limit consumption of alcohol (no more than 1 drink/day for women and 2 drinks/day for men)
  • Drink two or more cups of caffeinated coffee daily

Related blog entries:

 

Panels A & B show typical histologic findings: ballooned hepatocytes (arrows), inflammatory infiltrates (arrowheads), and fibrosis Panel C shows the relative distribution of NASH, cirrhosis, and hepatocellular carcinoma in U.S. Adults.

Research for Fatty Liver Disease

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Recently the AASLD Postgraduate Course discussed emerging treatments for nonalcoholic fatty liver disease/nonalchoholic steatohepatitis. From AASLD News: Emerging Treatments for NASH 

Key point:

  • Quentin Anstee: “It is important to remember that our patients with fatty liver disease will most likely die of cardiovascular disease, not liver disease.”

Four principles in treating nonalcoholic fatty liver disease (NAFLD) to address both cardiovascular and liver risks.

  • Target obesity with lifestyle changes and, possibly, bariatric surgery.
  • Target metabolic syndrome to reduce cardiovascular disease risk using medications with additional liver-directed benefits.
  • Target liver disease to prevent progression of steatohepatitis to fibrosis and cirrhosis.
  • Minimize downstream complications such as hepatocellular carcinoma.

More than 60 phase 3 trials are underway –Primary Therapeutic Targets:

  • PPAR signaling (insulin signaling, glucose and lipid metabolism, energy homeostasis, inflammation)
  • FXR signaling (insulin sensitivity, glucogenesis, lipogenesis)
  • ASK1 signaling (apoptosis)
  • CCR2/CCR5 signaling (inflammation and fibrogenesis).

Low FODMAP –Real World Experience

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HM Staduacher et al. Gastroenterol October 2017; 153: 936–47

Key finding:

  • In this randomized, placebo-controlled study with 104 patients with irritable bowel syndrome (IBS), the researchers spent only 10 minutes per patient teaching the low FODMAPs diet; yet 57% reported adequate relief of symptoms.

AGA Journals blog summary: Can a Diet Low in FODMAP Reduce IBS Symptoms in the Real World?

An excerpt:

Heidi Maria Staudacher et al aimed to investigate the effects of a diet low in FODMAPs compared with a sham diet in patients with IBS, and determine the effects of a probiotic on diet-induced alterations in the microbiota.

They performed a 2×2 factorial trial of 104 patients with IBS. Patients were either given counselling to follow a sham diet or diet low in FODMAPs for 4 weeks, but not the actual foods. Patients also received a placebo or multistrain probiotic formulation, resulting in 4 groups (27 receiving sham diet/placebo, 26 receiving sham diet/probiotic, 24 receiving low-FODMAP diet/placebo, and 27 receiving low-FODMAP diet/probiotic)…

In the per-protocol analysis, a significantly higher proportion of patients on the low-FODMAP diet had adequate symptom relief (61%) than in the sham diet group (39%).

The total mean IBS severity score was significantly lower for patients on the low-FODMAP diet (173 ± 95) than the sham diet (224 ± 89), but there was no significantly difference between patients given probiotic (207 ± 98) or placebo (192 ± 93).

Related blog posts:

 

Liver Articles: Short Takes

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DBE van Wessel et al. JPGN 2017; 65: 370-74.  This retrospective study showed an increase in biliary atresia incidence in preterm infants compared with full-term: 1.06 per 10,000 compared with 0.52/10,000. In addition, 4-year transplant-free survival rates were significantly worse at 21%, whereas 4-year survival rates was 61%. Clearance of jaundice (with Kasai) was achieved in only 23%.

Related post: Biliary Atresia More Common in Preterm Infants

ES Björnsson et al. Clin Gastroenterol Hepatol 2017; 15: 1635-36. This study examined response to steroids in 18 patients with drug-induced autoimmune hepatitis.  Key findings: 14 patients had elevated antinuclear antibodies & there were none with elevated smooth muscle antibodies. Infliximab was most frequent agent (n=11) and nitrofurantoin was other frequent agent (n=3).  Overall, 40% improved after discontinuation of medication, the remainder had prompt responses to corticosteroids.  Relapse did not occur when corticosteroids were discontinued.  Among the infliximab group, there was no evidence of liver injury after transitioning to alternative tumor necrosis factor-α inhibitor.

M Balwani et al. Hepatology 2017; 66: 1314-22. Acute Hepatic Porphyrias -Review. Current recommendations include gene sequencing to confirm all biochemical cases. Biochemical tests are spot urine testing of porphobilinogen (PBG), 5-aminolevulinic acid (ALA), and porphyrins. A normal urine PBG in symptomatic patients “excludes the three most common acute hepatic porphyrias.”  For those with abnormal studies, this reference is a handy.

S Wirth et al. Hepatology 2017; 66: 1102-10.  This study examined the effectiveness of sofosbuvir and weigh-based ribavirin dosing in 12-17 year olds with genotype 2 & 3 Hepatitis C infection.  Duration of treatment was 12 weeks for genotype 2 and 24 weeks for type 3.  Overall, SVR12 was achieved in 51 of 52 (98%); one patient with genotype 3 did not achieve SVR12.

Related post: New HCV Treatment Effective in Adolescents (Genotype 1 study)

F Kanwal et al. Gastroenterol 2017; 153: 996-1005. This study, a retrospective cohort of 22,500 VA patients treated for hepatitis C infection, showed that direct-acting antivirals (DAAs) lowered, but did not eliminate, the risk of hepatocellular carcinoma (HCC). Among the 87% who achieved an SVR, the adjusted hazard ratio for HCC was 0.28.  This was true as well as among patients with cirrhosis.. Hazard ratio for those with compensated cirrhosis was 0.32 compared with 0.18 among those without cirrhosis.

TPN Amino Acid Shortages Following Hurricane Maria

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Thanks to Kipp Ellsworth for this link: FDA Announcement Regarding Medical Product Shortages Related to Puerto Rico Production

An excerpt: the hurricane disrupted Baxter’s amino acids production facilities in Puerto Rico; Baxter is one of the largest manufacturers of this product serving the U.S. market. In order to help mitigate this shortage, the FDA has worked with Baxter to facilitate the temporary importation of amino acids for pediatric and adult formulations of IV amino acids from Baxter facilities in the United Kingdom and Italy.