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.

Pediatric Liver Transplantation: Past Time to Split

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A recent study (EK Hsu et al. Gastroentorol 2017; 153: 988-95, editorial 888-89) exposes some deep flaws in organ transplantation in U.S.

The retrospective study examined children on the U.S liver transplant wait-list from 2007-14.  This included 3852 pediatric candidates.  Key findings:

  • Of 27,831 adults who underwent transplantation, 1667 (6%) received livers from pediatric donors (<18 years)
  • Of children who died or were delisted, the centers caring for 173 (55%) had received an offer of 1 or more livers that was subsequently transplanted into another pediatric recipient.  The remaining 45% died or delisted with no offers. High-volume (>15 transplants per year) centers were more likely to accept an organ than a low-volume center (<5 transplants per year).
  • Only 29% of children received a split graft.  When a splittable adult liver graft was allocated to an adult the chance of it being used as a split was 0.6%.

Background:

  • Children have much lower survival rate than adults on waiting list. Of adults who died or delisted, 85% receive at least one transplant offer; whereas, nearly half of all children never even receive an offer.  Children who died/delisted had wait-time of 33 days compared with 92 days for adults who died/delisted.
  • Less than 10% of all liver transplant recipients are pediatric transplants.  Per editorial, “a measure that improves pediatric access by 20% would only reduce adult access by 2%.”
  • There are more than 100 pediatric liver transplant centers in U.S. Certainly, this improves convenience; however, per editorial:  “three-fourths are very low volume centers, performing <5 liver transplantations per year…Death on waiting list” occur 5 times more at low-volume transplantation centers.
  • In this study, only 29% of children received split livers; in comparison, in the UK, >80% receive either a split graft or living donor graft.

The editorial points out that splittable livers that are allocated to adults are virtually never split; this is either due to inconvenience or lack of expertise.  A small increase in liver splitting would dramatically lower the pediatric mortality wait list.  There is no incentive in the current system to split a liver/save a child’s life.

My take: The data from this study points out glaring problems in pediatric liver transplantation.

  1. Children are dying due to lack of prioritization.  Pediatric livers are going to adults.
  2. There is practically no splitting when liver organs are allocated to an adult.  Incentives to increase organ splitting would save many children from dying waiting for an organ.
  3. Large volume pediatric centers are much more likely to accept a liver offer for patients waiting at their centers.  There is an increased wait-list mortality at very low volume centers, perhaps due to lack of expertise and passing up viable organs.  Do hepatologists/surgeons at these centers explain this risk to families at their centers?

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>99% Accuracy in Non-Biopsy Diagnosis of Celiac Disease

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Another large study (KJ Werkstetter et al. Gastroenterol 2017; 153: 924-35) shows a high accuracy of diagnosing celiac disease (CD) without a biopsy when very high celiac titers are identified in symptomatic patients. A previous study (n=898) this year also showed similar findings: The Non-Biopsy Diagnosis of Pediatric Celiac Disease

The current study (2001-2014) identified 743 consecutive pediatric patients with positive celiac serology (TTG-IgA). Key findings:

  • If TTG-IgA was higher than 10-fold the upper limit of normal and a separate sample tested positive for endomysial antibodies, then non-biopsy approach had a positive predictive value >99.6%.  The authors utilized a variety of TTG-IgA assays.
  • The authors noted that HLA-DQ2/DQ8 typing did not improve the accuracy of CD diagnosis.  “Negative results for HLA-DQ2/DQ8 in patients with TGA or EMA positivity are most likely false negative …or due to very rare risk-allele combinations not recognized by the test systems.”
  • “At least 50% of affected children in clinical practice will benefit from this nonbiopsy approach, which reduces burden and risks of endoscopy and anesthesia” and is more cost-effective.

The authors’ conclusion: “allowing omission of biopsies enables a correct diagnosis of CD in symptomatic children if TTG-IgA exceed 10xULN and positive EMA-IgA confirms celiac disease autoimmunity in a second blood sample. If one of these criteria is not fulfilled, biopsy should be performed to confirm the diagnosis.”

My take: This study provides convincing data that CD diagnosis does NOT require an intestinal biopsy under specific conditions.

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Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

The MH Score: Separating primary Hemophagocytic Lymphohistiocytosis from Macrophage Activation Syndrome

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“Sincerity is the key to success. Once you can fake that, you’ve got it made.”

–Groucho Marx

The above quote is not particularly related to this blog post –but I like it.

A recent study (F Minoia et al. J Pediatr 2017; 189: 72-8) provides data supporting a scoring system which helps distinguish primary hemophagocytic lymphohistiocytosis (HLH) from macrophage activation syndrome (MAS).

Background: “By convention, secondary HLH seen in rheumatic disorders is termed macrophage activation syndrome…occurs most commonly in systemic juvenile idiopathic arthritis (sJIA).”  Both HLH and MAS are life-threatening, though HLH tends to be more severe.  The treatment for the two disorders is much different.

HLH typically develops in the first year of life, though some remain asymptomatic until later.  Identification of pathologic mutations (primary HLH is not a single disease) is considered the gold standard, but this “takes weeks to complete and is not available in many resource-limited areas.”

In this study, the authors reviewed clinical features from 362 patients with MAS and 258 patients with HLH to develop a scoring system that more readily distinguished these conditions.The data from 80% of the patients was used to construct the scoring system and then this was validated with the remaining 20%.  MH Score:

  • Age of onset, years:                              0 points if >1.6 yr, 37 points if ≤1.6 yr
  • Neutrophil count, x 10 to the 9th/L:      0 points if >1.4, 37 points if ≤1.4
  • Fibrinogen, mg/dL:                               0 points if >131, 15 points if ≤131
  • Splenomegaly:                                      0 points if no, 12 points if yes
  • Platelet count, x 10 to the 9th/L:           0 points if >78, 11 points if ≤78
  • Hemoglobin, g/dL:                                0 points if >8.3, 11 points if ≤8.3

The age of onset and severe neutropenia are weighted the most heavily as they most heavily influence the odds ratio of having HLH; with multivariate analysis (Table 3), age of onset ≤1.6 yrs had an OR of 40.3, and neutrophil count ≤1.4 had an OR of 39.3.  All of the other parameters had OR between 2.9 and 4.4.  Hepatomegaly favored HLH as well but was not independently associated with the diagnosis.

How to use this scoring system:

  • In this cohort, the MH score ranged from 0 to 123.  The median value was 97 for HLH and 12 for MAS.
  • A cutoff of ≥60 yielded a sensitivity of 91% and specificity of 93% for the diagnosis of HLH.  Higher values increased the probability of HLH further.

Most laboratory studies were more abnormal with HLH; however, both ferritin elevation and LDH elevation were more pronounced with MAS.  Median ferritin was 5353 with MAS and 2910 with HLH.  Median LDH was 1230 with MAS compared with 696 with HLH.

This study validated the MH score for distinguishing HLH from MAS associated with sJIA; this can allow early introduction of aggressive treatment and appropriate genetic/immunologic evaluation.  The applicability of the MH score for distinguishing HLH from other conditions is unclear.  Further prospective evaluation of the MH score is needed.

My take: This is a very helpful study and is likely to influence diagnostic workup and management of these sick patients. Due to the liver and spleen abnormalities, pediatric gastroenterologists need to be able to recognize both HLH and MAS.

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Breastfeeding: Protection from Inflammatory Bowel Disease

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Xu L, et al. Systematic review with meta-analysis: breastfeeding and the risk of Crohn’s disease and ulcerative colitis. Aliment Pharmacol Ther. 2017;46:780-789.

https://doi.org/10.1111/apt.14291Thanks to Mike Hart for this reference.

From abstract:

Results

A total of 35 studies were included in the final analysis, comprising 7536 individuals with CD, 7353 with UC and 330 222 controls. Ever being breastfed was associated with a lower risk of CD (OR 0.71, 95% CI 0.59-0.85) and UC (OR 0.78, 95% CI 0.67-0.91). While this inverse association was observed in all ethnicity groups, the magnitude of protection was significantly greater among Asians (OR 0.31, 95% CI 0.20-0.48) compared to Caucasians (OR 0.78, 95% CI 0.66-0.93; P = .0001) in CD. Breastfeeding duration showed a dose-dependent association, with strongest decrease in risk when breastfed for at least 12 months for CD (OR 0.20, 95% CI 0.08-0.50) and UC (OR 0.21, 95% CI 0.10-0.43) as compared to 3 or 6 months.

From associated editorial by David Rakel:

This meta-analysis of 35 studies shows that there is a dose–response protective effect of the duration of breastfeeding on inflammatory bowel disease. The association shows as much as an 80% reduction in risk for both Crohn’s disease and ulcerative colitis for breastfeeding more than 12 months.

Breast Feeding Graph

Inflammatory bowel disease arises from a complex set of interactions related to genetic susceptibility, environmental exposures, and a dysregulated immune response to dysbiotic intestinal microbiota, according to the study authors. These data will give us one more reason to encourage breastfeeding, ideally for a year or more.

Related blog post: Nutrition Week (Day 7) Connecting Diet and Epidemiology in IBD

 

 

Assessing Neonatal Jaundice with Smartphone App

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A recent study (Taylor JA, et al. Pediatrics 2017; 140 (3) e20170312) reports on the effectiveness of a smartphone app, BiliCam, to detect total serum bilirubin (TSB) in a diverse sample of newborns < 7 days old.  Thanks to Ben Gold for this reference.

BiliCam uses a calibration card which is placed on the infant’s sternum to standardize the color (and jaundice) reading in the photo; the image goes via the internet to a server for analysis.

Key findings:

  • Estimated bilirubin levels using BiliCam were compared with TSB levels in 530 newborns which included 20.8% African American,, 26.3% Hispanic and 21.2% Asian American
  • The overall correlation was 0.91 were similar among all ethnic groups with correlations ranging from 0.88 to 0.92
  •  The sensitivity of Bilicam was 84.6% is for identifying infants with a TSB in the high-risk zone of the Bhutani nomogram. The sensitivity was 100% for identifying TSB > 17 mg/dL. Specificities were 75.1% adn 76.4% respectively.

For more commentary on this article: AAP Journals Blog: Bilirubin phone apps –our future calls!

My take: This article indicates that a digital image with Smartphone app analysis is much more accurate in detecting jaundice that a visual assessment.

Prospective Outcome Data for Infants with Gastroschisis

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A recent study (BS Fullerton et al. J Pediatr 2017; 188: 192-7) reports outcome data from 4420 neonates with gastroschisis from 175 North Amercan centers.

This study, using prospectively-collected data from the Vermont Oxford Network, was restricted to infants with birth weights >1500 g and gestational age >28 weeks.

Key findings from this cohort:

  • Survival was 97.8%
  • Length of stay (LOS) 37 day median
  • Sepsis, confirmed with either positive blood culture or CSF culture, “was the only independent predictor of mortality.”
  • In addition to gastroschisis repair, abdominal surgery was needed in 22.3%
  • At discharge, 57.0% were <10% weight for age; whereas, only 37.2% were born small for gestational age.
  • There were no outcome differences based on mode of delivery (eg. vaginal vs. cesarean)
  • Other congenital anomalies were noted in many infants, with 5.8% had an intestinal atresia: 4.6% jejunal/ileal, 1.9% colonic, 0.4% duodenal atresia.

My take: This contemporary study shows excellent survival of neonates with gastroschisis.  Sepsis, need for additional surgery, and poor growth remain important challenges.

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Bile Acid Therapy -18 Year Study

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JE Heubi et al (JPGN 2017; 65: 321-6) performed a phase 3, open-label, nonrandomized trial on the efficacy and safety of oral cholic acid for patients with Zellweger Spectrum disorders (n=20) and patients with bile acid synthesis disorders (BASD) (n=50). Cholic acid dosing: 10-15 mg/kg/day. Most common BASD were 3β-HSD (n=35), and 5β-reductase (n=10).  Based on this work, cholic acid is an FDA-approved agent.

Key findings:

  • Urine bile acid metabolite scores improved (P<0.0001) with cholic acid
  • Transaminases improved (AST, ALT) (P<0.0001)
  • Growth parameters, improved with weight gain reaching statistical significance
  • “Liver biopsies showed either stable findings or histologic improvement in all parameters except bridging fibrosis”
  • No study drug-related serious adverse events were noted
  • With Zellweger spectrum disorders, it is important to note that “there is no evidence that treatment with cholic acid has any impact on the extrahepatic disease.”

My take: Cholic acid helps the liver in these disorders which is particularly important for BASD. It is unclear if this improves outcomes in patients with Zellweger spectrum disorders as it has not been shown to improve extrahepatic disease.

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