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.

Eosinophilic Esophagitis -Three Subtypes

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Eosinophilic oesophagitis endotype classification by molecular, clinical, and histopathological analyses: a cross-sectional study

T Shoda et al. The Lancet Gastroenterology & Hepatology, published online May 2, 2018. DOI: https://doi.org/10.1016/S2468-1253(18)30096-7

Abstract:

Background

Eosinophilic oesophagitis is understood in terms of quantifiable histological, endoscopic, and molecular features. Data are scant for inter-relations of these features and their potential to identify distinct disease endotypes. We aimed to identify clinical–pathological correlations between endoscopic and histological disease variables by transcription profiling of the oesophagus of patients with eosinophilic oesophagitis of varying severity and disease activity states.

Methods

We did a cross-sectional study across ten hospital sites in the USA associated with the Consortium of Eosinophilic Gastrointestinal Disease Researchers. We analysed oesophageal biopsy specimens taken from paediatric and adult patients with eosinophilic oesophagitis (discovery cohort), using the eosinophilic oesophagitis diagnostic panel (EDP), a set of 96 informative transcripts. Histological and endoscopic features were assessed by quantification of oesophageal eosinophils and use of the eosinophilic oesophagitis histology scoring system (HSS) and the eosinophilic oesophagitis endoscopic reference score (EREFS). Associations among the various histological, endoscopic, and molecular features were analysed by Spearman correlation. Results were replicated in a biologically independent, single-centre, validation cohort of patients with active eosinophilic oesophagitis.

Findings

The discovery cohort contained 185 samples and the validation cohort comprised 100 specimens. In the discovery cohort, EDP showed intersite consistency, significant correlation with oesophageal eosinophils (p<0·0001), and similar findings between paediatric and adult patients. Of eight HSS domains, basal zone hyperplasia correlated with the EDP (median Spearman ρ 0·47 [IQR 0·36–0·60]). Of five EREFS features, distal furrows correlated with the EDP (median Spearman ρ 0·42 [0·32–0·50]). By analysing active eosinophilic oesophagitis in the discovery cohort, the EDP identified three clusters associated with distinct endotypes (termed EoEe1–3) despite similar eosinophil levels. EoEe1 was associated with a normal-appearing oesophagus (risk ratio [RR] 3·27, 95% CI 1·04–10·27; p=0·0443), an inverse association with a history of oesophageal dilation (0·27, 0·09–0·82; p=0·0105) and showed relatively mild histological, endoscopic, and molecular changes. EoEe2 showed an inflammatory and steroid-refractory phenotype (RR 2·77, 95% CI 1·11–6·95; p=0·0376) and had the highest expression of inflammatory cytokines and steroid-responding genes. EoEe3 was associated with a narrow-calibre oesophagus (RR 7·98, 95% CI 1·84–34·64; p=0·0013) and adult onset (2·22, 1·19–4·12; p=0·0155), and showed the highest degree of endoscopic and histological severity and the lowest expression of epithelial differentiation genes. These endotypes were replicated in the validation cohort by clustering and with an eosinophilic oesophagitis endotype-prediction algorithm.

Interpretation

Our new disease classification stratifies patients with eosinophilic oesophagitis into subgroups with potential clinical and therapeutic significance and provides a framework for a precision medicine approach to eosinophilic oesophagitis.

Related blog entries:

Comprehensive 2018 AASLD Guidance for Chronic Hepatitis B

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NA Terrault et al. Hepatology 2018; 67: 1560-99. Here’s the full link: Update on Prevention, Diagnosis, and Treatment of Chronic Hepatitis B: AASLD 2018 Hepatitis B Guidance

Some of the key points:

Table 4 (pg 1565): provides a refresher on interpretation of serology

Table 5 (pg 1567): Children and Adults Who Are HBsAg Positive:

  • Can participate in all activities, including contact sports
  • Should not be excluded from daycare or school participation and should not be isolated from other children
  • Can share food and utensils and kiss others

Figure 1 (pg 1571) Treatment algorithms.

  • For both HBsAg-positive/HBeAg-positive and HBsAg-positive/HBeAg-negative patients, treatment is recommended if ALT ≥2 x ULN.
  • For both groups, treatment is NOT recommended for those with ALT ≤ULN and low HBV DNA levels (<20,000 IU/mL for HBeAg-positive and <2,000 IU/mL for HBeAg-negative).
  • In those who do not fall into these categories, ongoing monitoring is recommended

Figure 1 from AASLD Guidance Link

Guidance Statements for HCC Screening in HBsAg‐Positive Persons

  • All HBsAg‐positive patients and high risk adults (see page 1574) with cirrhosis should be screened with US examination with or without AFP every 6 months.
  • There are insufficient data to identify high‐risk groups for HCC in children. However, it is reasonable to screen HBsAg‐positive children and adolescents with advanced fibrosis (F3) or cirrhosis and those with a first‐degree family member with HCC using US examination with or without AFP every 6 months.

Treatment: 

  • In adults: The AASLD recommends peg‐IFN, entecavir, or tenofovir (TDF) as preferred initial therapy for adults with immune‐active CHB
  • In children: The AASLD suggests antiviral therapy in HBeAg‐positive children (ages 2 to <18 years) with both elevated ALT and measurable HBV‐DNA levels, with the goal of achieving sustained HBeAg seroconversion.

Perinatal transmission:

  • The AASLD suggests antiviral therapy to reduce the risk of perinatal transmission of HBV in HBsAg‐positive pregnant women with an HBV‐DNA level >200,000 IU/mL..The only antivirals studied in pregnant women are lamivudine, telbivudine, and TDF. Of these 3 options, TDF is preferred to minimize the risk of emergence of viral resistance during treatment. Interim studies show high efficacy of TDF in preventing mother‐to‐child transmission.
  • The infants of all HBsAg‐positive women should receive immunoprophylaxis (HBV vaccination with or without hepatitis B immunoglobulin, per World Heath Organization and Centers for Disease Control and Prevention recommendations)

Treatment & prevention of HBV reactivation in patients receiving immunosuppressive or cytotoxic drugs (section 6 pages 1577-9)

  • HBsAg and anti‐HBc (total or immunoglobulin G) testing should be performed in all persons before initiation of any immunosuppressive, cytotoxic, or immunomodulatory therapy.
  • HBsAg‐positive, anti‐HBc–positive patients should initiate anti‐HBV prophylaxis before immunosuppressive or cytotoxic therapy.
  • HBsAg‐negative, anti‐HBc–positive patients could be carefully monitored with ALT, HBV DNA, and HBsAg with the intent for on‐demand therapy, except for patients receiving anti‐CD20 antibody therapy (e.g., rituximab) or undergoing stem cell transplantation, for whom anti‐HBV prophylaxis is recommended.

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.

Sub-Analysis of DIAMOND Study

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K Watanabe et al. Clin Gastroenterol Hepatol 2018; 16: 542-9.

The DIAMOND study evaluated monotherapy with adalimumab (n=85) compared with combination therapy of adalimumab with azathioprine (n=91).

Key findings:

  • In this subanalysis of patients with moderate and severe Crohn’s disease (CD), endoscopic response (defined by SES-CD drop of at least 8 points or SES-CD <4) was significantly higher at week 26: 71.6% vs 54.4%. The OR for endoscopic response was 2.12 at week 26 with combination therapy.
  • At week 52 the endoscopic response difference was not statistically significant: 60% vs. 50%.
  • Similarly, mucosal healing was more common (but not statistically significant) in the combination group compared with monotherapy: 20.9% vs 103% at week 26, and 21.5% vs 12.2% at week 52.
  •  While not statistically significant, the combination group had ADA trough that was higher (7.6 compared with 6.5).

My take: The results described above for endoscopic responses and mucosal healing rates are depicted in figure 2 (I do not have a digital copy of figure or permission to use).  After one looks at this figure, depicting the data noted above, there certainly appears to be an advantage for the use of combination therapy in patients with moderate-to-severe CD.

Related blog posts:

 

 

I have not independently verified the claims on this tweet

Don’t Forget the Kidneys in Children with Intestinal Failure

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Increasingly, kidney problems are recognized in children with intestinal failure/short bowel syndrome who receive long-term parenteral nutrition.  A recent study (H Billing et al JPGN 2018; 66: 751-54) highlights the experience with this issue at a pediatric intestinal rehabilitation center in Germany.

Key findings:

  • Among 50 patients with a median age of 4.2 years, 76% had proteinuria
  • 30% had chronic kidney disease –indicated by reduced creatinine clearance of <90 min (1.73 squared)/min
  • Hypercalciuria was identified in 30 patients (60%)
  • Nephrocalcinosis was identified in 9 patients (18%)

The authors note that end-stage renal failure has not been reported in association with intestinal failure, though proteinuria is associated as a risk factor.

My take: This observational study shows a high frequency of kidney issues in children with intestinal failure. With improvements in survival, chronic kidney disease could become a more significant clinical issue.

 

Tweet below indicates need for careful nutrition input when children are placed on unusual diets, including the ketogenic diet.

Super Poopers –CCFA Take Steps 2018

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Yesterday, I was fortunate to participate in Crohn’s and Colitis Foundation of America (CCFA) “Take Steps” walk with a big contingent of our team.  A shout out to Melissa Sheffer who was honored as Adult Volunteer of the year and to Jacqueline Akin who was honored as a pediatric hero.

Melissa along with Dr. Larry Saripkin (not pictured but also at event/walk) have been the crucial volunteers to run Camp Oasis for the last 14 years.  Jacqueline said in her speech that she is followed by our team and also described some of the issues she has faced in trying to manage Crohn’s disease.

Also, I want to thank Jacob Schoeff and Dr. Dinesh Patel for team leadership and organizing our participation.  Great work!

For those so inclined, it’s not too late to donate to our CCFA team: CCFA Super Poopers Donation Link

Celecoxib as Safe as Naproxen and Ibuprofen

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Link to NPR article: FDA Affirms Safety of Painkiller Celebrex

An excerpt:

The FDA’s committee’s conclusion is based on the results of that study, which involved more than 24,000 patients with osteoarthritis and rheumatoid arthritis. One-third took celecoxib, which is only available by prescription. One-third took prescription doses of ibuprofen. The remaining third took prescription naproxen.

The study found no evidence that celecoxib poses any greater risk for causing heart attacks and strokes than ibuprofen or naproxen. Those medications are in category known as nonsteroidal anti-inflammatory drugs, or NSAIDs…

The study found the risk of dying, suffering a stroke or having a heart attack among patients taking celecoxib was 2.3 percent during a 30-month period, compared with 2.5 percent for naproxen and 2.7 percent for ibuprofen

Endoscopy for Graft-versus-host Disease

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Briefly noted: T Martensson et al. JPGN 2018; 66: 744-50.

This retrospective study with 44 children (81 procedures) examined the yield of endoscopy for graft-versus-host disease (GVHD).  They found that sigmoidoscopy had a sensitivity of 85% whereas Ileocolonoscopy OR combined EGD-sigmoidoscopy both had a sensitivity of 97.4%.  The authors, thus, advocate more extensive evaluation in the majority of children with possible GVHD.  “Sigmoidoscopy may be an approach to consider in severely ill children with contraindications to full endoscopy, for example, general anesthesia.”

Related blog post: Image Only: GVHD

Big Creek Greenway, near McFarland

Liver Shorts May 2018

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VL NG et al. J Pediatr 2018; 196: 139-47. This study with 148 children examined the neurodevelopmental outomes of young children with biliary atresia (ChiLDRen Study). Key finding: Children with their native livers were at increased risk for neurodevelopmental delays at 12 and 24 months.  This risk was more than 4-fold increased among those with unsuccessful Kasai procedure.

Related blog posts:

WS Lee et al. J Pediatr 2018; 196: 14-20. Updated review on hepatopulmonary synddrome (HPS) and portopulmonary hypertension (POPH).  Figure 1 graphically shows the difference in pathophysiology.  HPS hallmark is intrapulmonary vascular dilatation.  POPH is characterized by progressive remodeling of the wall (thickening & vasoconstriction) of small pulmonary arteries.

Related blog posts:

JA Woo Baidal et al. Hepatology; 2018; 67: 1339-47. This prospective cohort study with 528 children showed that increased Vitamin E intake in early childhood, based on validated food questionnaires, correlated with lower ALT values in mid-childhood.  Children with higher intakes “had lower odds of elevated mid-childhood ALT” (adjusted odds ratio of 0.62) when comparing quartiles 2-4 to the lowest quartile.  The authors note that Vitamin E is present in foods that are more often consumed in “healthful diets, such as wheat germ, almonds, spinach, and broccoli, as well as cooking oils.”

J Pfeiffenberger et al. Hepatology 2018; 67: 1261-69. The retrospective multicenter study with 282 pregnancies in 136 women with Wilson’s disease (WD), showed good outcomes. Aggravation of neurologic symptoms was rare (1%) (though tended to persist), liver test abnormalities (6%) resolved in all cases after delivery. Birth defect rate of 3% and spontaneous abortion rate of 26%; rthough, patients receiving treatment with zinc and D-penicillamine had lower spontaneous abortion rates, (10% and 17%, respectively) than those without treatment.  Chelation therapy resulted in no increase in the rate of birth defects compared to the general population.

Related blog posts:

F Bril et al. Clin Gastroenterol Hepatol 2018; 16: 558-66. This prospective study of adults with biopsy-proven NASH (52 with diabetes and 49 with prediabetes) found that pioglitazone treatment was associated with a reduction in the primary outcome, NAFLD activity score by 2 or more points, in 48% of those with type 2 diabetes and 46% of those with prediabetes. And, with a resolution of NASH in 44% and 26% respectively.

 

Big Creek Greenway near McFarland

From ImproveCareNow: Resources for Mind Body Interventions

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From ImproveCareNow: Resources for Mind Body Interventions

The above linked-website has links to many others for patients and providers: meditation, mindfulness, yoga and guided imagery.  The links on this page borrowed from Chelly Dykes and KT Park who credits Dr. Sindu Vellanki and Dr Ann Ming Yeh from Stanford.

 

Literature on these topics (also from ImproveCareNow): Mind Body Interventions and IBD

Mind Body Interventions and IBD – Journal Articles

Overview:

  • Yeh, A. M., Wren, A., & Golianu, B. (2017). Mind–Body Interventions for Pediatric Inflammatory Bowel Disease. Children, 4(4), 22. doi:10.3390/children4040022
  • Mindfulness/ Meditation/ Mindfulness based Stress Reduction (MBSR):
  • Kabat-Zinn, J., Lipworth, L., Burney, R., & Sellers, W. (1987). Four-Year Follow-Up of a Meditation-Based Program for the Self-Regulation of Chronic Pain: Treatment Outcomes and Compliance. The Clinical Journal of Pain, 3(1), 60.

**Note: This is an overview of MBSR, not IBD specific

Mindfulness:

  • Neilson, K., Ftanou, M., Monshat, K., Salzberg, M., Bell, S., Kamm, M. A., . . . Castle, D. (2016). A Controlled Study of a Group Mindfulness Intervention for Individuals Living With Inflammatory Bowel Disease. Inflammatory Bowel Diseases, 22(3), 694-701.
  • Jedel, S., Hoffman, A., Merriman, P., Swanson, B., Voigt, R., Rajan, K., . . . Keshavarzian, A. (2014). A Randomized Controlled Trial of Mindfulness-Based Stress Reduction to Prevent Flare-Up in Patients with Inactive Ulcerative Colitis. Digestion, 89(2), 142-155.
  • Hood, M. M., & Jedel, S. (2017). Mindfulness-Based Interventions in Inflammatory Bowel Disease. Gastroenterology Clinics of North America, 46(4), 859-874.
  • Berrill, J. W., Sadlier, M., Hood, K., & Green, J. T. (2014). Mindfulness-based therapy for inflammatory bowel disease patients with functional abdominal symptoms or high perceived stress levels. Journal of Crohns and Colitis,8(9), 945-955. doi:10.1016/j.crohns.2014.01.018
  • Gerbarg, P. L., Jacob, V. E., Stevens, L., Bosworth, B. P., Chabouni, F., Defilippis, E. M., . . . Scherl, E. J. (2015). The Effect of Breathing, Movement, and Meditation on Psychological and Physical Symptoms and Inflammatory Biomarkers in Inflammatory Bowel Disease.Inflammatory Bowel Diseases,21(12), 2886-2896.

Clinical Hypnosis:

  • Keefer, L., Taft, T. H., Kiebles, J. L., Martinovich, Z., Barrett, T. A., & Palsson, O. S. (2013). Gut-directed hypnotherapy significantly augments clinical remission in quiescent ulcerative colitis. Alimentary Pharmacology & Therapeutics,38(7), 761-771.
  • Mawdsley, J. E., Jenkins, D. G., Macey, M. G., Langmead, L., & Rampton, D. S. (2008). The Effect of Hypnosis on Systemic and Rectal Mucosal Measures of Inflammation in Ulcerative Colitis. The American Journal of Gastroenterology,103(6), 1460-1469.
  • Shaoul, R., Sukhotnik, I., & Mogilner, J. (2009). Hypnosis as an Adjuvant Treatment for Children With Inflammatory Bowel Disease. Journal of Developmental & Behavioral Pediatrics,30(3), 268.
  • Vlieger, A., Govers, A., Frankenhuis, C., & Benninga, M. (2010). Hypnotherapy for children with functional abdominal pain or irritable bowel syndrome: Long term follow-up. European Journal of Integrative Medicine,2(4), 191.

Yoga: 

IBS + Yoga:

  • Schumann, D., Anheyer, D., Lauche, R., Dobos, G. Langhorst, J., Cramer, H. Effect of Yoga in the Therapy of Irritable Bowel Syndrome: A Systematic Review. Clin. Gastroenterol. Hepatol.  2016, 14, 1720-1731.
  • Selvan, S. R., Kavuri, V., Selvan, P., Malamud, A., & Raghuram, N. (2015). Randomized clinical trial study of Yoga therapy for Irritable Bowel Syndrome (IBS). European Journal of Integrative Medicine,7, 23.
  • Kuttner, L., Chambers, C., Hardial, J., Israel, D., Jacobson, K., Evans, K. A Randomized Trial of Yoga for Adolescents with Irritable Bowel Syndrome. Pain Research & Management 2006, 11, 217-223.
  • Evans, S., Lung, K., Seidman, L., Sternlieb, B., Zeltzer, L., & Tsao, J. (2014). (567) Iyengar yoga for adolescents and young adults with irritable bowel syndrome (IBS). J. Pediatri. Gastroenterol. Nutri. 2014, 59, 244-253.

IBD + Yoga:

 

Concurrent Infections in Inflammatory Bowel Disease Flares

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Briefly noted: Y Hanada et al. Clin Gastroenterol Hepatol 2018; 16: 528-33.

In this retrospective review with 9247 patients with IBD, the incidence of bacterial pathogens (non-C diff) identified was <3% of those who were tested; in this group (n=25), Aeromonas was detected in 8,Salmonella in 7, Plesiomonas in 4, Campylobacter in 2, and Yersinia in 2.  From authors: “These infections did not have a significant negative impact on patient outcomes.  Given these findings, routine testing for infections other than CDI is not recommended.”

Chattahoochee River