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.

10 Years of Intractable Diarrhea

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A recent report (JPGN 2014; 59: 571-76) from Turkey reviewed their experience with intractable diarrhea of infancy from 2000-2010.  This retrospective review included 60 hospitalized patients.

Key findings:

  • Carbohydrate malabsorption, including glucose-galactose malabsorption, and food allergy accounted for 11 patients (18%) each.
  • 16 patients (27%) had no definitive diagnosis.
  • Other etiologies included infections, inflammatory bowel disease, autoimmune enteropathy, microvillus inclusion disease, tufting enteropathy, short bowel syndrome, cystic fibrosis, proprotein convertase 1 deficiency, congenital disorder of glycosylation, abetalipoproteinemia.

The authors provide a useful diagnostic algorithm (Figure 1).

Related blog post:

Four IBD Articles –Four Teaching Points

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  1. Inflamm Bowel Dis 2014; 20: 1891-1901
  2. Inflamm Bowel Dis 2014; 20: 1996-2003
  3. Inflamm Bowel Dis 2014; 20: 2013-21.
  4. Inflamm Bowel Dis 2014; 20: 2056-66.

The first article is listed as a ‘basic science’ article.  However, it has direct relevance to the clinical problem of anti-TNF-induced psoriasiform skin lesions.  The article notes that this problem affects about 5% of patients treated with anti-TNF agents.  The authors found that IL-36γ and IL-17C are increased in anti-TNF-induced psoriasiform skin lesions of patients with Crohn’s disease (n=13 patients).  An important clinical point was that 7 of these patients with “severe anti-TNF induced skin lesions were successfully treated with the IL-12/IL-23 neutralizing antibody ustekinumab.”  This was superior to topical steroids or topical tacrolimus.

The second article is a proof-in-principle type article showing that proactive measurements of infliximab (IFX) levels may improve outcomes.  This retrospective observational study examined 48 patients who had proactive IFX levels. In 12 of 48, IFX dosing was escalated after the first proactive monitoring.  In addition, over the study period, 15% of patients had their dosing lowered. In those with proactive monitoring, the probability of remaining on IFX was >80%.  Those patients who achieved trough levels >5 mcg/mL had >90% probability of remaining on IFX therapy.  The authors hypothesize that better IFX levels may reduce anti-infliximab levels.

The third article examines carbohydrate intake in relation to the development of Crohn’s disease (CD) and ulcerative colitis (UC). The authors utilized the “EPIC” cohort (European Prospective Investigation into Cancer and Nutrition) (Public Health Nutr 2002; 5: 1113-24).  among 401,326 enrollees at recruitment, the dietary intakes of carbohydrates were measured using validated food frequency questionnaires. In this cohort, 110 developed CD and 244 developed UC during followup. Key finding: there was no significant risk for IBD based on total carbohydrate intake.  This study does not exclude the possibility that specific carbohydrates could have an etiological role.

The fourth article, a case-control study (2002-2011),  examines risk factors for endoscopy-associated perforation and perforation-associated complications (PAC) in patients with and without IBD. n=217,334 lower endoscopies (with 9518 in IBD patients).  Perforation rates: 18.91 per 10,000 and 2.50 per 10,000 for IBD and non-IBD endoscopy respectively.  The use os systemic corticosteroids at the time of endoscopy was associated with a 13 times greater risk for PAC.

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Anti-Tumor Necrosis Factor Therapies and Cochrane Reviews

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A recent article (Inflamm Bowel Dis 2014; 20: 2132-41) reviews the best available evidence on anti-TNF therapies.  This article emerged from a Cochrane collaboration session at Digestive Diseases Week (DDW) in 2013.

Key points:

  • “There is insufficient evidence to recommend ECI (early combined immunosuppression)) for every newly diagnosed patient, although it may be justifiable in some “high-risk” patients.”
  • With Crohn’s disease, combination of infliximab and azathioprine significantly improved remission, steroid-free remission, and mucosal healing rates compared with infliximab alone.
  • “A recent Cochrane review has shown that infliximab, adalimumab, and certolizumab are all effective…The choice of TNF-α antagonist depends on adherence, patient preference, mode of delivery, and cost.“
  • Elective switching of TNF-α antagonists: in patients who are doing well, elective switching “may be associated with loss of both tolerance and efficacy.”  “Dose intensification or early treatment termination was observed in 47% of patients who switched to adalimumab after an ongoing response to scheduled maintenance infliximab therapy compared with 16% of patients who remained on infliximab maintenance therapy.” 28% of ADA patients discontinued therapy compared with 2% of IFX patients.
  • When to stop therapy: among patients in deep remission >6 months who stopped, relapse occurred in 43.9% over 1 year.
  • Patients who take thiopurines or biologics (IFX or ADA) have an increased risk of nonmelanoma skin cancer. Odds ratio, compared to controls, as high as 6.75 for combination therapy (>365 days).
  • Lymphoma: the Cochrane review “found no statistically significant difference in the incidence of lymphoma between biologics and control treatment…and data from the TREAT registry also demonstrated no apparent signal for TNF-α antagonist (i.e. infliximab)-related lymphoma or overall malignancy.”
  • There has been incremental risk of Non-Hodgkin’s lymphoma and hepatosplenic T-cell lymphoma with azathioprine (thiopurines).

Related blog posts:

Other articles briefly noted:

Inflamm Bowel Dis 2014; 20: 2142-50. “Approach and management of patients with chronic hepatitis B and hepatitis C during the course of inflammatory bowel disease.”

Inflamm Bowel Dis 2014; 20: 2151-56.  Use of cyclosporin and tacrolimus in inflammatory bowel disease.  Checking hepatitis B surface antigen, surface antibody, and core antibody are recommended at the time of diagnosis of IBD. Algorithm for managing hepatitis B serology is given in Figure 1.

New Normal for Ulcerative Colitis

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A recent study (Clin Gastroenterol Hepatol 2014; 12: 1887-93) shows that patients with ulcerative colitis (UC) with subclinical activity, based on fecal calprotectin levels, improve with mesalamine escalation.  DEAR, the acronym for this study,  stands for Dose Escalation And Remission.

Methods: The researchers screened 119 patients with UC who were considered to be in remission based on the Simple Clinical Colitis Activity Index score. 52 patients who had calprotectin > 50 mcg/g and were receiving no more that  3 g/day of mesalamine were identified and switched to a mesalamine  MMX 2.4 g/day dose for 6 weeks.  Then the group was divided into an escalation group (4.8 g/day) or control group (continued with 2.4 g/day) for an additional 6 weeks.

Key findings:

  • 26.9% of the escalation group and 3.8% of the control group achieved a calprotectin <50 mcg/g.
  • 52.6% of the escalation group and 15.8% of the control group achieved a calprotectin <100 mcg/g.
  • 76.9% of the escalation group and 16.7% of the control group achieved a calprotectin <200 mcg/g.

This study shows that higher doses of mesalamine were more effective in improving the calprotectin biomarker; however, the exact target value for calprotectin is not entirely clear.  This study is in agreement with several others which have suggested a dose-response relationship with mesalamine therapy. This study suggests that a “quiescent” ulcerative colitis by scoring indices may overestimate the extent of colitis control.  However, the associated editorial (pg 1894) cautions that “the current data are not sufficient to warrant the use of mesalamine dose escalation in patients with UC in clinical remission who have an increased FC (fecal calprotectin) concentration greater than 50 mcg/kg.”

Also noted: Clin Gastroenterol Hepatol 2014; 12: 1865-70.  Prospective study of 59 patients with UC with clinical and endoscopic remission.  18 (30.5%) had histologic inflammation which correlated with elevated fecal calprotectin: median 278 mcg/g compared with 68 mcg/g for those without histologic inflammation.

Take-away message: If histologic inflammation is important, then fecal calprotectin can help identify this in patients otherwise considered to be in remission.

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Methotrexate Abstract: Subcutaneous vs. Oral Administration

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A recent abstract (Link: Gut doi:10.1136/gutjnl-2014-307964) indicates that there may be some advantages with subcutaneous methotrexate compared with oral administration, especially at the onset of treatment.

Here’s the abstract (thanks to KT Park for sharing this abstract on his twitter feed):

Efficacy of oral methotrexate in paediatric Crohn’s disease: a multicentre propensity score study

Background Oral methotrexate (MTX) administration avoids weekly injections, reduces costs and may improve quality of life of patients with Crohn’s disease (CD), especially children. Routes of administration have never been systematically compared in CD. We aimed to compare effectiveness and safety of orally (PO) versus subcutaneously (SC) administered MTX in paediatric CD.

Methods 226 children with CD treated with oral or subcutaneous MTX were included in a multicentre, retrospective 1-year cohort study (62% boys, mean age 13.8±2.8 years, 88% previous thiopurines). 38 (17%) were initially commenced on oral, 98 (43%) started subcutaneous and switched to oral and 90 (40%) were treated with subcutaneous only. Matching and ‘doubly robust’ weighted regression models were based on the propensity score method, controlling for confounding-by-indication bias. 11/23 pretreatment variables were different between the groups, but the propensity score modelling successfully balanced the treatment groups.

Results 76 children (34%) had sustained steroid-free remission with a difference that did not reach significance between the PO and the SC groups (weighted OR=1.72 (95% CI 0.5 to 5.9); p=0.52). There were no differences in need for treatment escalation (p=0.24), elevated liver enzymes (p=0.59) or nausea (p=0.85). Height velocity was lower in the PO group (p=0.006) and time to remission was delayed in the PO group (p=0.036; Fleming (0, 1) test).

Conclusions In this largest paediatric CD cohort to date, SC administered MTX was superior to PO, but only in some of the outcomes and with a modest effect size. Therefore, it may be reasonable to consider switching children in complete remission treated with subcutaneous MTX to the oral route with close monitoring of inflammatory markers and growth.

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What Better Care Looks Like -Five Examples

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From Harvard Business Review and the New England Journal of Medicine: Five examples of Better Care

  1. Increased transparency with patient feedback at University of Utah
  2. Shared responsibility to coordinate care experience at Mayo Clinic
  3. Teamwork with all members of health care team at Northwestern
  4. Addressing socioeconomic barriers at Contra Costa
  5. Consolidating care in London to specialized centers to improve outcomes and costs (with stroke)

What sets your institution apart from others?

“Show Don’t Tell” –Colonoscopy Prep Instructions

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A recent study, summarized in this link– Gastroenterology and Endoscopy News, indicates that providing an 11 minute video with colonoscopy prep instructions was more effective than written instructions.  Not only were the cleanouts better, but this resulted in better outcomes including higher adenoma detection rate and higher rates of completed colonosocpy.

Here’s an excerpt:

Dr. Bearelly and his colleagues randomized 298 individuals scheduled for screening colonoscopy to receive either the practice’s usual written instructions, or to receive the paper handout plus an instructional video (right). The 11-minute video—burned on a disk —covers the same instructions as the written materials, but in an interactive format that depicts a typical patient asking questions of one of the practice’s doctors.

The quality of bowel preparation between the two groups differed significantly (P=0.0098). Cecal intubation was 96% in the intervention group compared with 89% in the control group, and the adenoma detection rate was 53% and 42% in the two groups, respectively.

Patients in the intervention group had a Boston Bowel Preparation Score (BBPS) of 6.99±1.87, whereas those in the control group had a score of 6.43±2.54, although the difference was not statistically significant. A BBPS of 6, with a minimum of 2 in each segment, was considered adequate.

Take-home message:  Video instructions for colonoscopy are worthwhile.  In pediatrics, variability in cleanout regimens is a limiting factor.

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PEG vs Lactulose in Hepatic Encephalopathy

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In a study (JAMA Intern Med. Published online September 22, 2014. doi:10.1001/jamainternmed.2014.4746) with 50 participants, PEG was more effective than standard therapy of lactulose for hepatic encephalopathy.  PEG vs Lactulose (HELP study) Abstract.

Here’s an excerpt:

Design, Setting, and Participants  The HELP (Hepatic Encephalopathy: Lactulose vs Polyethylene Glycol 3350-Electrolyte Solution) study is a randomized clinical trial in an academic tertiary hospital of 50 patients with cirrhosis (of 186 screened) admitted for HE.

Interventions  Participants were block randomized to receive treatment with PEG, 4-L dose (n = 25), or standard-of-care lactulose (n = 25) during hospitalization…

Results  Thirteen of 25 patients in the standard therapy arm (52%) had an improvement of 1 or more in HESA score, thus meeting the primary outcome measure, compared with 21 of 23 evaluated patients receiving PEG (91%) (P < .01)… The median time for HE resolution was 2 days for standard therapy and 1 day for PEG (P = .01). Adverse events were uncommon, and none was definitely study related.

Conclusions and Relevance  PEG led to more rapid HE resolution than standard therapy, suggesting that PEG may be superior to standard lactulose therapy in patients with cirrhosis hospitalized for acute HE.

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Looking More Closely at a Persistent Question

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Virtually everyday, families that I care for are trying to ascertain the link between their GI symptoms and the foods in their diet.  Many authoritative recommendations on irritable bowel have concluded that “food allergies (symptoms caused by an immune response) are rarely the culprit in IBS patients. Most IBS patients with food-related symptoms have food sensitivities or intolerances, which are not caused by an immune response.” (From Univ Virginia Irritable Bowel Diet PDF)

Whether the process is a sensitivity or an immune-reaction, many patients are quite sensitive to certain foods and many have had improvement with a low FODMAPs diet.

A much closer look at this problem with confocal laser endomicroscopy (CLE), in a pilot study (Gastroenterol 2014; 147: 1012-20), has shown measurable changes within five minutes of a food challenge that takes place during an endoscopy.  In this study, the researchers examined 36 patients with IBS who had suspected food intolerance and 10 control patients with Barrett’s esophagus.  Then during an endoscopy, the researchers used provoking solutions of cow’s milk, wheat, yeast, or soy.  The subjects had CLE before and after the challenges. To enhance visualization of changes, subjects had fluorescein dye injected intravenously prior to examination of the duodenum.

Results

  • In 22 of 36 patients, the challenges were considered positive.  These patients had mucosal changes including increase in intraepithelial lymphocytes, followed by disruption of the villi tips/shedding of cells, then fluorescein leakage into the lumen.
  • None of the control patients exhibited these changes.
  • 19 of 22 patients with positive challenges had a >50% reduction, after 4-weeks, in symptom score with individualized diet based on inciting antigen.

Bottomline:

This provocative study indicates that subtle mucosal changes can occur in a number of IBS patients in a quick and direct response to food challenges.  Perhaps when we look closer with technologies like CLE we will find more answers as to why certain foods provoke symptoms in adults and children with IBS.

Related blog posts:

Also noted –web-based information on gastroparesis: