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.

Updated AASLD guidelines and Ascites

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The American Association for the Study of Liver Diseases (AASLD) updates all of its practice guidelines annually (AASLD: Practice Guidelines).  In adults with ascites due to cirrhosis, a recent publication highlights some of the more recent updates (Hepatology 2013; 57: 1651-53).

  • In adults, typically “cirrhosis cures hypertension.”  In addition, a prospective study has shown that propranolol shortens survival in patients with refractory ascites.  So, “consideration should be given to discontinuing beta-blockers or not initiating beta-blockers in those patients with refractory ascites.”
  • “Percutaneous endoscopic gastrostomy is advised against in patients with cirrhosis and ascites.”
  • “A meta-analysis of 17 trials involving 1225 patients..” demonstrates a reduction in mortality with albumin infusion after large-volume paracentesis.  Odds ratio of death with albumin infusion was 0.64.
  • There is an increasing prevalence of bacterial resistance due to widespread use of quinolines to prevent spontaneous bacterial peritonitis (SBP).  “It is prudent to limit prophylactic antibiotics to patients with well-defined criteria for SBP prophylaxis.”
  • A new biomarker (not available in U.S.) assists with the diagnosis of hepatorenal syndrome: urinary neutrophil gelatinase-associated lipocalin.
  • Vaptans are discussed in the update.  The largest trial with cirrhotic patients “demonstrated no clinical benefit in long-term management of ascites” and may increase mortality.

Norovirus Impact on Young Children

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As noted in a previous blog (Norovirus -now more important than rotavirus | gutsandgrowth), Norovirus has become the most important cause of gastroenteritis in children younger than 5 years.  More data to back up that claim has been published (NEJM 2013; 368: 1121-30).

The authors examined laboratory-confirmed cases of norovirus in children younger than 5 years with acute gastroenteritis in hospitals, emergency departments, and outpatient clinical settings during the years 2009 and 2010.  Using the New Vaccine Surveillance Network (NVSN), the authors undertook a 2-year prospective population-based survey with a catchment population of more than 141,000.  The specific sites included county populations around the University of Rochester, Vanderbilt University, and Cincinnati Children’s.

Results:

  • Norovirus was detected in 21% of children with acute gastroenteritis (2009-2010); it was also detected in 4% of healthy controls.
  • The age group with the highest rates of norovirus infection in this study were 6-18 months of age.
  • The GII.4 Minerva strain was most predominant strain in 2009 and GII.4 New Orleans in 2010. (In 2012, a novel GII.4 Sydney variant has emerged).
  • Rotavirus was identified in 12% of children with acute gastroenteritis (2009-2010).
  • Using this data, the authors extrapolated national estimates (for norovirus) of 14,000  hospitalizations per year (in this age group), 281,000 emergency room visits, and 627,000 outpatient visits.
  • The estimated costs exceed more than $273 million.

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Predicting duration of reflux symptoms in babies

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A recent study identified two factors on multichannel intraluminal impedance pH monitoring (MII/pH) that correlated with the duration of gastroesophageal reflux symptoms in newborns (J Pediatr 2013; 162: 770-5).

This study examined 64 newborns who underwent MII/pH in the first weeks of life and then were enrolled in followup at 1, 3, 6, 9, 12, 18. 24, and 36 months. 53 patients completed the three-year study.

These patients were enrolled consecutively.  All preterm infants had to have a minimum postmenstrual age of 36 weeks.  Other criteria included a MII/pH study with a minimum duration of 19 hours, absence of GERD pharmacology for at least 1 week, and absence of infection, metabolic disease or central nervous system disease.

Results:

  • Impedance bolus exposure index (IBEI) and proximal reflux frequency positively correlated with duration of GERD symptoms.
  • IBEI was 1.45 in the short duration group (0-3 months), 1.85 in the medium duration group (4-9 months) and 2.46 in the long duration group (> 9 months).
  • Proximal reflux frequency (events/hour) was 1.56 in the short duration group (0-3 months), 1.95 in the medium duration group (4-9 months) and 2.38 in the long duration group (> 9 months).
  • Overall, one-half of patients were asymptomatic within the fifth month of age and the vast majority were asymptomatic by one year of age.
  • Weakly acidic events but not acid reflux events were significant in determining the differences in IBEI and proximal reflux.  As such, this study adds weight to the idea that acid blockers have little benefit in the first months of life.

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N-acetylcysteine for Acute Liver Failure

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A study which took 8 years to complete (2001-2009) and involved more than 20 pediatric liver transplant centers has shown that N-acetylcysteine (NAC) is NOT effective for nonacetaminophen acute liver failure in the pediatric population (Hepatology 2013; 57: 1542-49).

Eligible patients were drawn from a registry of pediatric acute liver failure (PALF) patients.  Among 607 who were enrolled in the registry, 271 were eligible for the NAC trial and 184 of these patients (families) agreed to participate.  The most common reasons for patients to be ineligible for the study included acetaminophen toxicity, previous NAC treatment, sepsis, and “reason unknown.”

The design of the study was doubly masked with patients stratified by age and hepatic encephalopathy.  Patients either received intravenous NAC (150 mg/kg/d) or D5W for up to 7 consecutive days.

Key findings:

  • No significant difference in 1-year survival: 73% of NAC patients and 82% of placebo patients
  • NAC patients had lower 1-year liver transplant free survival (p = 0.03): 35% in NAC group compared to 53% of placebo patients.

The study did have several limitations.  Despite the lengthy enrollment period, the absolute number of patients was only 92 in each group.  In addition, there were differences in the diagnoses in both groups and the ages of the groups, though these were unlikely to change the results.  With regard to diagnoses, both groups had ~60% with an indeterminate reason for PALF.  However, the NAC group had an increased number with metabolic diseases (14% compared with 5% in placebo group); the most common metabolic disease was Wilson’s disease (7 in NAC group and 3 in placebo group).  The NAC group had a median age of 3.7 years compared with 4.5 years for the placebo group.

Another limitation was in testing for acetaminophen-cysteine adducts (A-CA) which can be used as a marker of acetaminophen exposure.  This was performed retrospectively in 84 of the participants.  A-CA was positive in 9 (six from placebo and three from treatment arm).  Again, this was unlikely to change the results as there were no statistical differences in clinical features of those who were tested for A-CA compared with those who were not.

In some ways, the results are surprising due to prospective studies in adults showing benefit of NAC in ALF and a previous retrospective uncontrolled pediatric study suggesting efficacy in PALF.  Ultimately, this study proves again that pediatric patients are not “small adults” and highlights the need for prospective pediatric drug trials.

Bottom-Line:

NAC works for acetaminophen-induced ALF but is not helpful for other causes of PALF.

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Lunchroom Makeover

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A recent pilot study indicates that $50 and three hours can increase the chances that teens will eat their fruits and vegetables (J Pediatr 2013; 162: 867-9).  While the US Department of Agriculture has mandated alterations in what foods that schools offer for lunch, schools cannot force students to eat specific foods.  As such, the authors tried changing the convenience, attractiveness, and ‘normative nature of healthy foods’ in the lunchroom. These changes are part of a behavioral science called “libertarian paternalism.”

These field studies took place at two schools in western New York with students at 7-12 grade levels.  After implementing changes in the lunchrooms, researchers recorded tray waste on multiple dates.

Specific changes included the following:

Improved convenience:

  • “Healthy convenience line” with only submarine sandwiches and healthier sides (fruits/vegetables)
  • Salad served in see-through to-go containers

Improved attractiveness:

  • Lunch menu posted with nice color photos of fruits and vegetables
  • Fruit displayed in nice bowls or tiered stands

Normative behavior:

  • Verbal prompts by staff: “Would you like to try…”, “No veggie? How about…” “You can get another side with your meal. How about grabbing a piece of fruit?”
  • “Last chance for Fruit” sign displayed next to fruit basket at the cash register

The impact of the “smarter lunchroom:” actual fruit consumption increased by 18% and vegetable consumption increased by 23%.  The limitations of this study: no control school, did not track individual consumption, and small number of measured days.

Related blog link:

Global increases in IBD incidence

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Two more studies have shown increasing incidence of pediatric inflammatory bowel disease.

First in Victoria, Australia (mostly Melbourne) (Inflamm Bowel Dis 2013; 19: 1-6).

Over a 60-year span (1950-2009), a retrospective review was undertaken of ulcerative colitis (UC) pediatric patients. In total, 342 children were diagnosed with UC. Key finding: The number of reported cases increased by 11-fold during the study period with a marked increase since 1990 (0.15 –>1.61/100,000).  In addition, recently diagnosed children have had more extensive disease.

Next in Spain (Inflamm Bowel Dis 2013; 19: 73-80).

This retrospective study from hospitals’ databases looked at the incidence between 1996-2009 in the pediatric population (<18 years).  A total of 2107 patients were identified: 1165 with Crohn’s disease, 788 ulcerative colitis, and 154 IBD unclassified. Median age at diagnosis was 12.3 years.  Key finding: in the last 14 years, pediatric IBD incidence has almost tripled (0.9 –>2.8/100,000).

Both of these studies have limitations related to large retrospective reviews in terms of potential problems with capturing all of the patients and the potential for misdiagnosis.  However, the trend is clear.  In addition, these studies show incidence rates comparable to several other Western studies.  The increasing incidence of IBD ‘argue for a common environmental factor in their pathogenesis.’  While interest has focused on microbial factors, the basis for this increased incidence currently remains elusive.

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Nuance in Celiac Serology Interpretation

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A recent study adds additional nuance to the interpretation of celiac serology (Clin Gastroenterol Hepatol 2013; 11: 398-403).

In this study the authors analyzed anti-TTG IgA levels from 104 consecutive pediatric and adult patients who were not IgA deficient.  The study took place between 2000-2009.  In addition, samples from 537 consecutive controls were available for comparison.

The study determined the likelihood of having celiac disease based on antibody level from four different companies and pre-test clinical factors.  The general population pretest probability was 1%; the pretest probability for their population was 6% if their were gastrointestinal complaints, 14% if weight loss/small stature was present, 11% for patients with anemia/iron deficiency, and 9% for patients with malabsorption.

Key findings:

Even in those with high antibody titers (>10-fold normal), if they were asymptomatic, only 53%-75% had celiac disease (depending on the individual assay).  That is, >10-fold elevation with some commercial assays did not correspond to >10-fold elevation in all of the assays leading to variable probabilities.

In patients with low level elevations (1-3 fold times the cut-off level), the probability of having celiac disease in asymptomatic individuals varied from 1% to 7%.  Thus, mild elevations in TTG IgA are not highly predictive in this asymptomatic population.  However, in those with pretest probability of 14%, the frequency of celiac disease varied among the four assays from 14% to 56%.

Take home message:  Not all assays for celiac disease are comparable.  While very high serology levels (>10 fold) are associated with celiac disease, in asymptomatic patients as few as 53% may have celiac disease.

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Button Battery Algorithm Link

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The following website has a useful button battery algorithm (thanks to JL for forwarding this link):

One important point is that in an asymptomatic patient, a button battery in the stomach can be left alone if no coingestion with a magnet.  If gastric battery is > 15 mm and child is less than 6 year,  the recommendation is to check xray in 4 days and remove if still in stomach or whenever there are symptoms.
Of course, a button battery in the esophagus is a true endoscopic emergency. Recognizing that it is a button battery and not a coin can alter the outcome.
Related blog links:
Another link on foreign bodies, 2011: Postgraduate Course Syllabus – Slides, only – NASPGHAN.org (Look for the slides from Marsha Kay)

Fish Oil, IFALD, and Liver Fibrosis

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While there has been a lot of enthusiasm for the use of fish oil as a potential breakthrough for intestinal failure-associated liver disease, this has been based largely on the use of surrogate markers of liver disease and based on comparisons with the historical use of conventional intravenous lipids.  The latter problem has been discussed before on this blog (see links below).

A recent study begins to address the issue of surrogate markers by reinforcing the viewpoint that improvements in bilirubin and aminotransferases may not translate into improvement in liver fibrosis or other clinically-meaningful outcomes (JPGN 2013; 56: 364-69).  A previous pediatric study (J Pediatr 2010; 156: 327-31) showed failure of regression of hepatic fibrosis in 2 children receiving FOE therapy.

In this study, the authors sequentially examined 6 children on fish-oil lipid emulsions (FOE) who underwent multiple liver biopsies.  In this cohort, 5 of 6 children had gastroschisis and the mean gestational age was 35 weeks.  Median intestinal (small bowel) length beyond the ligament of Treitz was 26 cm and most children retained about 2/3rds of their colon.  Liver biopsies were obtained at the time of other open abdominal operations (eg. serial transverse enteroplasty, stoma takedown).

Key results:

  • Liver fibrosis persisted in 2 cases, progressed in 3 cases, and regressed in 1 case.
  • Histology and biochemistries indicated improvement in cholestasis and inflammation.
  • One patient has weaned off parenteral nutrition, two patients underwent isolated small bowel transplantation due to recurrent line infections, and three patients receive 25-40% of their calories parenterally.

The biggest limitation of this study besides the small number of enrolled patients was the relatively short  time period that was studied.  Only one patient who was studied had data reported for FOE more than 36 weeks.  The oldest age of any patient at the time of their last biopsy was 131 weeks old.

Take-home points:

  • “There is no direct evidence to support any one [proposed theoretical benefit of FOE] as clinically meaningful as yet.”
  • “Lipid minimization strategies are also effective in reducing cholestasis.”
  • “Many of the biopsies taken right at the time of FOE initiation” showed significant fibrosis which “speaks to how quickly fibrosis can develop.” One child had stage 2 fibrosis at 14 weeks of life.
  • “The biochemical resolution of cholestasis is at best a weak surrogate marker ..for…enteral independence and overall survival.”  “These findings make a strong case for early referral of children with short bowel syndrome to specialized intestinal rehabilitation centers.”

Related blog posts:

True red flags in recurrent abdominal pain

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For pediatricians and pediatric gastroenterologists alike, identifying which children need additional workup for recurrent abdominal pain (RAP) is facilitated by recognizing “red flags.”  “Red flags” are clinical features that indicate a higher likelihood of a nonfunctional disorder.  A recent study notes that reports of waking from sleep and joint pains do not distinguish functional from nonfunctional causes of RAP (J Pediatr 2013; 162: 783-7).

This study, performed between 2005 to 2008, had patients presenting to an outpatient pediatric gastroenterology clinic for RAP prospectively complete a detailed questionnaire. Data, though, was extracted retrospectively. In this population (n=606), 85% were Caucasian.  After their evaluation, patients with functional GI diseases (FGID, n=478) were compared with patients confirmed with Crohn’s disease (CD, n=128).  All FGIDs underwent biochemical testing, 41% had upper endoscopy, and 32% underwent colonoscopy.

Additional key findings:

  • Using a tree analysis, the cumulative sensitivity for Crohn’s disease was 54% with the presence of anemia, 78% when blood in stool was added to anemia, and 94% when weight loss was added as well.
  • FGID patients were more likely to report stress and headaches, more likely to have family history of FGID, and less likely to have anemia, hematochezia, or growth issues.
  • FGID patients were more likely to experience vomiting.

The sensitivity and specificity of these symptoms/signs will vary based on the population.  For a general pediatric clinic, it is likely that the sensitivity of these red flags would remain high; the specificity would likely be lower than in a pediatric gastroenterology office due to the increased prevalence of functional diseases in the general pediatric setting.

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