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.

Misdirection: False-postive Urine Cannaboid Screen due to Pantoprazole

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First of all, this post is not a joke for April 1st. But if you have a good story to tell, please feel free to comment -I’ll share a story at the bottom of this post.

A case report (Felton D et al. Pediatrics 2015; 135: 2014-16) makes a few useful points regarding testing for cannaboids in a patient admitted for cyclic vomiting syndrome.

  1. Intravenous pantoprazole could lead to a false-positive urine cannaboid screen.
  2. Cannabis hyperemesis syndrome should be included in the differential diagnosis for cyclic vomiting. (see previous blog: Think Like a Doctor -Another Reason for Cyclic Vomiting …)
  3. Don’t order every test on the differential diagnosis (my point -not the authors).

With regard to the final point, this particular case report describes a highly-impaired 13 year old with previous diagnoses of intrauterine stroke, global developmental delays, and seizures; she was nonverbal and nonambulatory.  Therefore, despite a positive urine screen, it is not surprising that the confirmatory testing for cannabis via gas chromatography-mass spectrometry was negative.

Related blog posts:

On a side note, several years ago we had a little fun in the spirit of April 1st.  One of our neighbors had been complaining for years that they had not received ‘yard of the month’ but had lived in the neighborhood for more than 16 years. So, one year when they were out of town, we managed to borrow the ‘yard of the month’ sign, placed it in their yard, and snapped a picture.  With the collusion of a different neighbor who sends out the monthly announcement, our neighbors were informed of the recognition of their yard. It was definitely a good laugh.  At the same time, I’m a little paranoid about potential payback.

 

 

Predicting Response to Topical Steroids in Eosinophilic Esophagitis

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A recent study (Wolf WA, et al. Clin Gastroenterol Hepatol 2015; 13: 45-58) examined 221 patients in a retrospective cohort study to determine how effective topical steroids were in the treatment of eosinophilic esophagitis (EoE).  The authors studied these patients from 2006-2013; the majority received budesonide (63%) and the remainder received fluticasone; the typical dosing was 0.5 mg-1 mg twice daily and 440-880 mcg twice daily, respectively. 129 (58%) of the participants were >18 years.

Key findings:

  • 57% had histologic response with <15 eos/hpf
  • Refractory patients “were difficult to treat with dietary and second-line pharmacologic therapies, with less than half responding even after multiple second-line therapies.” The most successful second-line approach was diet: 6 of 16 (38%) had improved histology (<15 eos/hpf).  Higher doses of topical agents were effective in 2 of 14 (14%) and alternative topical agent was effective in 2 of 7 patients (29%).
  • Dilatation at the time of disease presentation (25% of the study cohort) correlated with poor clinical outcome.  Only 40% (20 of 50) had a histologic response.
  • High tissue levels of tryptase and eotaxin-3 increased the likelihood of a steroid response.

As this was a retrospective study, there were several weaknesses.

Take-home message: The findings from this large cohort show that more than 40% of patients did not have a favorable histologic response.  Some recent studies indicate that higher doses of steroids may be effective, but this may be influenced by the proportion of individuals with advanced fibrostenotic disease.

Related blog posts:

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications/diets (along with potential adverse effects) should be confirmed by prescribing physician/nutritionist.  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.

Chicago's Bean

Chicago’s Bean

Lower Endoscopic Thresholds for Thrombocytopenia

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According to an advances in endoscopy report (Ross, WA. Gastroenterology Hepatology 2015; 11: 115-17), lower platelet thresholds are indicated for many endoscopic procedures.  The author works at MD Anderson Cancer Center in Houston.

Key points:

  • “We feel that the traditional threshold of 50,000 platelets/microliter that many doctors adhere to or aim for should be put aside, and a lower platelet threshold of perhaps 25,000 or 30,000 platelets/microliter should be employed for endoscopic procedures, including biopsies.“
  • “We found that therapeutic maneuvers could be performed to control bleeding.”
  • “This change would require fewer platelet transfusions to prepare a patient for endoscopy.”
  • Based on their published experience (Krishna SG, et al. “Saftey of endoscopic interventions in patients with thrombocytopenia.” Gastrointest Endosc 2014; 80: 425-34), the author notes that “polypectomy could probably be performed with a platelet count under 50,000/microliter, likely in the 30,000-40,000/microliter range, particularly if the polyp was small (<10 mm).”  They caution that cold snare technique may be safer in this setting but is not suitable for larger polyps.
  • Other preventative measures include stopping aspirin use, limiting the number and size of biopsies, and using non thermal means to help stop bleeding, such as clips or injections.
  • “Performing an endoscopic procedure in a patient with an extremely low platelet count, such as 5000/microliter, is associated with a high risk of bleeding.”

“If the procedure is just a simple biopsy, a platelet count of 25,000/microliter to 30,000/microliter should suffice.”

Take-home message: While the data that the author references is derived from adults, it is likely that in pediatrics that endoscopy, if needed, can be performed in patients with platelet counts less than 50,000/microliter.

Herbal Medicines for IBD and IBS

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A nice review (Holtmann G, Talley NJ. Clin Gastroenterol Hepatol 2015; 13: 422-32) provides a summary of the experience of herbal medicines for disorders that include irritable bowel syndrome (IBS), functional dyspepsia, and inflammatory bowel disease (IBD).

A recurring theme in the review is that herbal medicines are poorly studied and vary greatly in the quality of their manufacturing.  “Physicians and regulators need to remain very cautious about the use of herbal remedies.” The available trials, with a long list of plant extracts, are summarized in tables in the review.

Specific points:

  • “A meta-analysis also showed that supplementation of peppermint oil, in addition to pharmacologic standard treatments, was of benefit to both constipation-predominant IBS and diarrhea-predominant IBS patients.”
  • “The use os STW5 [iberogast] also has been found to be effective compared with placebo in the treatment of IBS symptoms.”
  • Very small clinical studies have suggested possible efficacy of aloe vera and curcumin in the treatment of IBD.
  • Adverse effects: “there are numerous case reports on adverse events related to herbal medicines.” Some of these have been severe.
  • “The main driver for the use of herbal and complementary medicines is the unmet need of patients.” However, given that these preparations are non patentable, “there is limited investment of producers.”

Bottomline: There is little financial incentive for companies to determine more conclusively whether these agents are effective for functional disorders or for inflammatory bowel disease.

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More on Adalimumab (Humira) in Pediatrics

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A recent ‘observational cohort’ study (Cozijnsen M, et al. JPGN 2015; 60: 205-10) provides more information regarding the use of adalimumab in pediatrics.  The authors attempted to identify all Dutch patients <18 years of age with Crohn’s disease who received adalimumab after infliximab therapy.  Excluded patients were those with “bad treatment adherence,” conflicting comorbidity, and previous participation in prospective study by Hyams et al Gastroenterol 2012; 143: 365-74 (Related blog post: Adalimumab for children with Crohn’s disease | gutsandgrowth).

Key findings:

  • 53 patients met the inclusion criteria.  12 received monotherapy with adalimumab; cotherapy in 21 with thiopurines, 11 with methotrexate, 7 with steroids, and 2 with enteral nutrition.
  • Median followup was only 12 months.
  • Remission noted in 34 (64%) patients based on either wPCDAI or PGA (physician global assessment) after a median of 3.3 months.  Remission was durable in 50% of these patients for 2 years.
  • Adalimumab failure was noted in 18 (34%).  Only 3 patients in this study were primary infliximab nonresponders and only 1/3 responded to adalimumab.
  • One serious adverse event (infection) was reported.

One weakness of this study (& many others) is its reliance on clinical disease activity indices rather than more precise measures of mucosal healing.

Take-home point: This small study provides some information about the utility of adalimumab in clinical practice in pediatrics.  As noted in other studies, those with a loss of response to infliximab, rather than primary nonresponders, appear to have a more favorable response to adalimumab. In addition, the glaring weakness in this study (i.e. small number of participants) validates the rationale behind efforts like ImproveCareNow which can generate information quickly from a large patient population.

Related study: “Levels of Drug and Antidrug Antibodies are Associated with Outcome of Interventions After Loss of Response to Infliximab or Adalimumab.” Yanai H, et al. Clin Gastroenterol Hepatol 2015; 13: 522-30. Retrospective study of 247 adult and pediatric patients. Key findings:

  • Patients with adequate trough levels (>4.5 mcg/mL for adalimumab, >3.8 mcg/mL for infliximab) “identified patients who failed to respond to an increase in dosage or a switch to another anti-TNF agent with 90% specificity.”
  • “Levels of antibody against adalimumab >4 mcg/mL-eq or antibodies against infliximab >9 mcg/mL-eq identified patients who did not respond to an increased drug dosage with 90% specificity.” These patients were likely to benefit by switching to an alternative anti-TNF.

Related study: Clin Gastroenterol Hepatol 2015; 13: 539-47.  Trough levels of infliximab (>3 mcg/mL) at week 30 was associated with improved outcomes, including mucosal healing and corticosteroid-free remission.

Briefly noted from ImproveCareNow: Dotson JL et al. “Feasibility and Validity of the Pediatric Ulcerative Colitis Activity Index in Routine Clinical Practice.” JPGN 2015; 60: 200-04.  This study, with 2503 patients, found that the PUCAI was completed in 96% if visits.  The PUCAI correlated with PGA chain scores.

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Don’t be Fooled About Withdrawing Immunomodulator Cotherapy -Look Past the Headline

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The coverage on a recent study (Clinical Gastroenterology and Hepatology 2015: 13(3): 514-521.e4) suggests that it should be fine to stop immunomodulator co-therapy.  I recommend reading the entire study (or at least this blog post)–you will probably come to a different conclusion.
Brief summary from AGA website: Withdrawal of Immuonomodulators after Co-therapy Does Not Reduce Trough Level of Infliximab in Crohn’s Patients

“The addition of immunomodulators increases the efficacy of maintenance therapy with infliximab for up to one year in patients with Crohn’s disease who have not been previously treated with immunomodulators. However, there are questions about the effect of withdrawing immunomodulator therapy from these patients. David Drobne and colleagues studied the effects of treatment with infliximab and immunomodulators (co-treatment) and then immunomodulator withdrawal on long-term outcomes of patients, as well as trough levels of infliximab and formation of anti-infliximab antibodies (ATI). Reporting in Clinical Gastroenterology and Hepatology, they find that, in a retrospective analysis, withdrawal of immunomodulators after at least six months (median, 13 months) of co-treatment with infliximab does not reduce the trough levels of infliximab in patients with Crohn’s disease. Detectable trough levels of infliximab at the time of immunomodulator withdrawal are associated with long-term response.”

Clinical Gastroenterology and Hepatology 2015: 13(3): 514-521.e4

Some additional details:

This was a retrospective open-label cohort study with 223 patients and median followup of 34 months. At baseline, 65 received infliximab (IFX) monotherapy and 158  received co-therapy with an immunomodulator (46 methotrexate, 112 thiopurine).  Immunomodulators were withdrawn “only in patients with durable response (ongoing clinical benefit with lasting disease control with low C-reactive protein [CRP] [below 10 mg/L]).”  Among the 158 on co-therapy, 117 reached a durable response and had withdrawal of immunomodulator after >6 months of combination therapy (median time 13 months).

Key findings:

  • At baseline, co-therapy patients, compared to monotherapy patients, had higher IFX trough levels (adjusted mean increase of 1.44-fold) and lower likelihood of antibodies to infliximab (ATI): 35/158 (22%) compared with 25/65 (38%), P=.01.
  • When immunomodulator was withdrawn, IFX levels remained stable: before 3.2 mcg/mL compared with after 3.7 mcg/mL. However, 45 of 117 (38%) required increasing doses of IFX and 21 of 117 (18%) discontinued IFX.
  • Trough levels of IFX and CRP  were most strongly associated with response to IFX dosing on monotherapy.
  • “Only 9 of 74 patients (12%) with detectable IFX trough levels at the time of immunomodulator withdrawal developed undetectable IFX trough levels during the subsequent follow-up.”
  • None of the 27 patients with IFX trough level >5 mcg/mL at time of immunomodulator withdrawal lost response to IFX during median follow-up of 29 months.

Though the headlines covering this article have suggested that IFX levels will stay stable when immunomodulators are withdrawn after >6 months, the authors proposed algorithm only recommends withdrawal for those with IFX trough level >5 mcg/mL.  In addition, the data showed that a large number of patients required dose escalation and/or lost detectable IFX levels. Despite their proposed algorithm to withdraw in this small group, the authors further backtrack in their conclusion:  “a prospective parallel group trial during a period of 5-10 years in a large group of patients is required to ascertain the real long-term benefit to risk ratio of continuing combined infliximab and immunomodulator treatment.”

Bottomline: If a patient is doing well, withdrawing immunomodulator co-therapy still has risks. I worry that the misleading reporting of this article will result in detrimental outcomes.

Related blog posts:

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.

 

Fatty Liver at Birth

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A provocative study (Patel KR, White FV, Deutsh GH. JPGN 2015; 60: 152-58) shows that hepatic steatosis/fatty liver is prevalent at birth in at-risk stillborns.

The authors retrospectively examined autospy results from 33 stillborns (20-40 weeks) delivered to women with diabetes (pregestational or gestational) along with 48 age-matched controls.  The majority of women (54%) were African American women; 27% were white and 9% were hispanic.

Key findings:

  • Hepatic steatosis was common and severe in the stillborns of diabetic women.  Prevalence: 78.8% (26/33) compared with 16.6% (8/48) of controls.
  • No direct correlation was identified between steatosis and glycemic control.

Whether nonalcoholic fatty liver disease (NAFLD) begins at birth is not known and what happens to the fat in newborns with hepatic steatosis is not clear.  This study indicates that maternal diabetes may increase the risk of NAFLD.

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Methotrexate Dosing in Dual Therapy

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A recent retrospective study (DOI: http://dx.doi.org/10.1093/ecco-jcc/jjv027 first published online: 23 January 2015 -reference from KT Park’s twitter feed) has suggested that high-dose methotrexate (MTX) (15-25 mg/week) is more effective than low-dose MTX (≤12.5 mg/week) as part of dual therapy for inflammatory bowel disease.

Here’s the abstract: Optimal Doses of Methotrexate

Background and Aims: Methotrexate is sometimes used as part of combination therapy for the treatment of inflammatory bowel disease (IBD), however the optimal MTX dose for combination therapy has not been established. This study compared the efficacy of lower dose and higher dose methotrexate with anti-TNF therapy among IBD patients.

Methods: Retrospective chart review was performed of 88 IBD patients at our center between 2010-2013. Low-dose methotrexate was defined as ≤ 12.5mg/week and high-dose methotrexate as 15-25mg/week. Patients who met the criteria for clinical remission (Harvey-Bradshaw Index ≤ 4, Simple Clinical Colitis Activity Index ≤ 2) at baseline were followed for up to 42 months. Chart review occurred in six-month intervals. The primary outcome was consecutive months in remission prior to relapse. Secondary outcomes included other indicators of worsening disease (endoscopic inflammation, steroid use, therapy escalation/addition, or surgery) and adverse events. Regression analysis and Kaplan-Meier survival analysis were completed.

Results: We identified 73 (83%) dual-therapy patients, of which 32 low-dose and 14 high-dose individuals achieved remission. When compared with high-dose patients, low-dose patients were more likely to relapse (log-rank test, P<0.01). Secondary indicators of worsening disease occurred during 34.4% of low-dose review periods and 31.4% of High-dose review periods (P=0.67). 3/52 (6%) low-dose patients and 3/21 (14%) high-dose patients (P=0.34) discontinued methotrexate therapy due to adverse events.

Conclusions: When combined with anti-TNF therapy, methotrexate at doses of >12.5mg/week were more effective at maintaining clinical remission than lower doses. These findings will guide management of combination therapy in IBD patients.

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Do You Think Fruit Drinks Are Healthy?

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According to a recent report in USA Today, a large number of parents have been misled into thinking that sugary beverages and fruit drinks are healthy. Here’s an excerpt:

That’s the conclusion of a new study from the Rudd Center for Food Policy and Obesity at University of Connecticut, published today in Public Health Nutrition.

Many parents believe that drinks with high amounts of added sugar — particularly fruit drinks, sports drinks and flavored water — are “healthy” options for kids, according to the report, funded by the Robert Wood Johnson Foundation, which focuses on improving health and health care…

The vast majority of parents give kids sugary drinks regularly…Equally significant, nearly half of parents surveyed rated flavored waters as healthy, and more than one-quarter considered fruit drinks and sports drinks to be healthy…

Parents said they were particularly influenced by nutritional claims appearing on the packages — such as claims that the items are “real” or “natural” or contained vitamin C or antioxidants, or were low in sodium or calories.

Bottomline: This information reinforces the fact that many parents do not realize basic nutrition information.

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Cyclophilin Inhbitor for Chronic Hepatitis B

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From AGAblog: A New Approach to Hepatitis B?

Cyclophilins are involved in multiple steps of the hepatitis B virus (HBV) life cycle in hepatocytes—cyclophilin inhibitors reduce viral replication and HBV envelope protein production and secretion, researchers report in the February issue of Gastroenterology. The cyclophilin inhibitor alisporivir, combined with the HBV polymerase inhibitor, reduces markers of HBV infection and HBV replication in cells, revealing a possible new therapeutic approach for chronic hepatitis B.