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.

Autoimmune Liver Disease in Children with Sickle Cell Disease

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A recent retrospective study (S Jitaruch et al. J Pediatr 2017; 189: 79-85) documents the important association of autoimmune liver disease in children with sickle cell disease (SCD).  I have seen  children with hemoglobinopathy and autoimmune hepatitis.

Key findings:

  • 13 of 77 patients with SCD were diagnosed with autoimmune liver disease
  • 2 patients presented with acute liver failure
  • 6 patients had cholangiopathy on cholangiogram “suggesting autoimmune sclerosing cholangitis”
  • At median follow-up of 3.8 years, 5 achieved full remission, 4 partial remission, 1 had liver transplant, 1 died of subdural hemorrhage (prior to liver disease treatment), and 2 were lost to followup

My take: this report is a good reminder that though there are a good number of reasons for abnormal liver blood tests in children with SCD, it is important to follow these children closely and to obtain serology (including ANCA) in those with persistent elevations.

Related blog post: Blood is not enough

South Kaibab Trail at the basin of the Grand Canyon (Colorado River)

 

Cytosponge for Eosinophilic Esophagitis

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A recent prospective study (DA Katzka et al. Am J Gastroenterol 2017; 112: 1538-44 -thanks to Ben Gold for this reference) provided more information regarding the potential utility of the cytosponge for eosinophilic esophagitis (EoE); the cytosponge has been studied for Barrett’s esophagus.

Background: 86 adult patients were recruited; 6 could not swallow sponge.  In the remainder, 105 procedures were performed comparing the cytosponge to standard endoscopic biopsies. The cytosponge technique can be completed in ~5 minutes without sedation. “All that is required is centrifuging the cytosponge specimen in its preservative to create a pellet followed by routine paraffin embedding and processing.”

Key findings:

  • Cytosponge was considered to have adequate specimen in 102 of 105 cases, compared with 104 of 105 with endoscopic sampling
  • Using a cutoff of <15 eos/hpf for inactive disease, the authors found that the cytosponge had a sensitivity of 75% and a specificity of 86%.
  • Six patients had active EoE on cytosponge with negative endoscopic biopsies.
  • 14 patients with active EoE with endoscopic biopsies had <15 eos/hpf with cytosponge
  • No complications were noted with cytosponge.

The sensitivity of 75% is likely due to inadequate contact between cytosponge and esophageal wall which could be related to technique, especially in those with a normal caliber esophagus.

My take: The cytosponge appears to identify active EoE in the majority of adult patients.  In those with abnormal cytosponge, the likelihood of active EoE would be very high; as such, it could be a useful biomarker.  It is still probable that many with normal cytosponge result would need endoscopy due to suboptimal sensitivity.

Related blog posts:

NEJM 2017; 377: e22. In this patient with lingual papillomas, hx/o melenoma, and both hyperplastic and adenomatous polyps, a genetic mutation identifying Cowden syndrome was identified.

Fatty Acid Intake and Risk of Ulcerative Colitis Flare

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A recent study (Barnes EL et al. Clin Gastroenterol Hepatol 2017; 15: 1390-6) found an association between the intake of certain fatty acids and the risk of an ulcerative colitis flare.  This is nicely summarized in the AGA Journals Blog.

Here’s the link: Does Consumption of Certain Fatty Acids Increase Risk of Ulcerative Colitis Flares?

Here’s an excerpt:

Diets with high levels of fatty acids such as myristic acid (found in palm oil, coconut oil, and dairy fats) increased risk of flare in patients with ulcerative colitis (UC), researchers report in the September issue of Clinical Gastroenterology and Hepatology. Their findings, from a prospective study of more than 400 patients in remission during treatment with aminosalicylates, could guide future studies of supplements or compounds that reduce risk of flares in patients with UC in remission…

Edward L. Barnes et al performed a prospective study of dietary patterns among 412 patients, from 25 sites, with UC in remission during monotherapy with an aminosalicylate (mesalamine, sulfasalazine, or balsalazide for at least 3 months before enrollment). Patients completed a validated food frequency questionnaire (on consumption of dairy, fruits, vegetables, eggs, meat, fish, cereals, breads, and starches, beverages, sweets, and baked goods) at enrollment and were followed for 12 months…

Forty-five patients (11%) had a relapse of UC within 1 year of study enrollment… In multivariable analysis, higher intake of myristic acid (odds ratio, 3.01) and alpha linolenic acid (odds ratio, 5.50) were associated with increased risk of relapse, although a dose–response relationship was retained only for myristic acid intake.

Other foods previously implicated in flares of UC, such as processed meat, alcohol, and foods high in sulfur, were not associated with an increased risk of flare.

Related blog posts:

From Andy Warhol Exhibit at the High Museum

Infant Feeding, Opportunity, and Asthma

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A recent study (A Kloop et al. J Pediatr 2017; 190: 192-9) examined the relationship between mode of infant feeding and the development of asthma.  The authors used prospective data from 3296 Canadian children in the Canadian Healthy Infant Longitudinal Development (“CHILD” study) cohort.

Key finding:

  • “Compared with infants who received direct breast milk only [at 3 months of age], those who received some expressed milk had a 43% increased odds [of asthma at 3 years of life] …and those who received only formula had a 79% increased odds.”

The authors speculate that the direct breastfeeding may offer some advantages over expressed breast milk:

  • There may be alteration in breast milk components with storage
  • A nursing infant may trigger an increased immune response and be directly exposed to some beneficial commensal bacteria

Since this is an observational study and patients were not randomized there may be other unrecognized confounding variables.

Another study in the same issue (AF Beck et al. J Pediatr 2017; 190: 200-6) assessed whether the Child Opportunity Index (COI) was associated with asthma outcomes in a retrospective cohort of 5462 children in Hamilton County, Ohio.  The COI (see below for the measures in this index) has previously been linked to life expectancy, low birth weight, and prematurity.  Interestingly, one can go to diversitydatakids.org to see how this affects your location (here is the link for a heat map of this index in the Atlanta area: Atlanta COI)

Key finding:

  • Median hospitalization rates varied based on COI –those with very high opportunity had a rate of 1.8 per 1000.  The other quintiles of COI were the following: high opportunity 2.1, moderate opportunity 4.6, low opportunity 7.6, and very low 9.1

My take: The first study indicates that direct breastfeeding is associated with lower rates of asthma.  The second study shows that issues related to education, environment, and social/poverty have an enormous impact on need for asthma-related hospitalization.

 

 

Costs of Biologics for Inflammatory Bowel Disease

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A recent study examines the market share and costs of biologic therapies for inflammatory bowel disease:

Excerpt from abstract:

The average biologic-taking patient accounted for $25 275 PMPY in 2007 and $36 051 PMPY in 2015. The average paediatric biologic-taking patient accounted for $23 616 PMPY in 2007 and $41 109 PMPY in 2015. In all patients, the share of costs for biologics increased from 72.9% in 2007 to 85.7% in 2015 (81.7% in 2007 to 94.9% in 2015 in paediatrics).

Conclusion

The vast majority of costs allocated to out-patient IBD medications in the USA is attributed to increasing use of biologic therapies despite the relative minority of biologic-taking patients.

My take: Biologic therapies are costly but also very effective.

Related Blog Posts:

 

The Original Anti-TNF Therapy: Thalidomide

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A recent study (M Lazzerini et al. Clin Gastroenterol Hepatol 2017; 15: 1382-9) used data from 2 multicenter trials of 70 children to assess the efficacy of thalidomide in pediatric patients with refractory inflammatory bowel disease (37 with Crohn’s disease, 23 with ulcerative colitis)

Key findings:

  • 42 patients (60%) had clinical remission & 45 (64%) had clinical response at week 8
  • 38 patients (54%) had clinical remission or response at week 52. 29 of these patients had mucosal healing (no erosions or ulcerations) & 20 patients had histologic healing
  • 7 patients dropped out from study prior to 52 weeks due to side effects (n=5) or clinical relapse (n=2)

My take: I have not used thalidomide therapy and remain concerned about long term side effects (eg. peripheral neuropathy).  Though, the authors are correct that its safety “may be acceptable compared with the safety of other” treatments, especially if there are few remaining options.

Related blog posts:

“Data-free Zone” and mHealth

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A recent study (J Kamgno et al. NEJM 2017; 377: 2044-52) used an innovative cell-phone-based device (the LoaScope) to improve treatment of onchocerciasis (river blindness).

Background (summarized in editorial: pg 2088-90): Ivermectin has been distributed in Africa since 1988 to treat onchocerciasis; in fact, the 2015, Nobel Prize in Medicine was shared by the discoverers of ivermectin.  However, in 1996, it was recognized that central nervous system adverse events were occurring in ivermectin-treated patients with coexistent Loa loa infection.

Kamgno et al show that not treating patients with L loa counts >20,000 microfilariae per mL helps target ivermectin to those who will benefit.  The LoaScope identified 340 persons who were at high risk for serious adverse events; the authors estimate that 62 serious central nervous system complications and 8 deaths were avoided with this approach.

Despite the apparent success of this mobile Health (mHealth) application, a separate editorial cautions that most mHealth has little data to support its use (A Roess.  NEJM 2017; 377: 2010-11). Key points:

  • To date, more than 1200 mHealth tools or apps have been catalogued
  • Determining which are effective is difficult  With breastfeeding, there are >340 apps, yet only “15 had any evidence supporting their use, and that was from pilot evaluations.:
  • Most apps involve data collection and delivering health education messages.  The latter are usually one-way messages. “The evidence to support their rapid and widespread use is limited.”
  • mHealth in remote areas may enhance collaboration; though, practical infrastructure problems like poor wireless networks and unreliable electricity hamper their utility.
  • mHealth could improve point-of-care diagnostics. Current products include blood-glucose monitors, blood-pressure monitors, and electrocardiography
  • While many have suggested these apps will be cost-effective, these analyses typically do not evaluate the costs of misinformation and the diverse workforce requirements needed for implementation

My take (with help from editorial): mHealth tools are here and increasing.  Advances like the LoaScope for treating river blindness has been shown to improve outcomes.  Before recommending other mHealth tools, we need to insist on adequate evaluation or we will “arrive in an increasingly fragmented mHealth landscaped littered with poor-quality, unproven apps.”

Related blog posts:

Sunrise at the Grand Canyon’s South Rim

Will We Still Need Liver Biopsies to Diagnose Biliary Atresia in a Few Years?

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A recent study (C Lertudomphonwanit, R Moura, L Fei, Y Zhang, S Gutta, L Yang, KE Bove, P Shivakumar, JA Bezerra. Sci Transl Med. 2017; 9: eaan8462) may change how we diagnose biliary atresia (BA) and provides an insight into potential pathogenesis. Link to study: Large-scale proteomics identifies MMP-7 as a sentinel of epithelial injury and of biliary atresia

Using large-scale proteomics, the authors screened 1129 proteins in a discovery cohort (n=70) of patients with BA.  They identified several proteins that were increased with BA. Matrix metalloproteinase-7 (MMP-7) was the lead biomarker.  Subsequently, they used two additional validation cohorts.  Human subjects were infants in enrolled in the Prospective Database of Infants with Cholestasis (PROBE) which is part of the NIDDK-funded ChiLDRen (www.childrennetwork.org).

Key findings:

  • 76 proteins were significantly overexpressed or underexpressed in BA compared with children with intrahepatic cholestasis (IHC).
  • MMP-7 was more accurate than gamma glutamyltranspeptidase (GGT).  The combination of MMP-7 and GGT had a AUROC of 0.94 in validation cohorts.
  • The authors further studied the role of MMP-7 by immunostaining and found it primarily was detected in cholangiocytes of intrahepatic bile ducts in infants with BA.  It was also identified in a few hematopoietic cells.
  • MMP-7 expression in the liver did not correlate with fibrosis.
  • MMP-7 serum levels increased in neonatal mice after bile duct epithelial injury induced by intraperitoneal rotavirus administration.
  • Using a mice model, they found that a MMP-7 inhibitor (batimastat) could block the development of BA in a mouse model (in 86% of cases) compared with 0% in control mice.
  • Overall, the authors note that coupled with GGT, MMP-7 serum levels result in “sensitivity and specificity of 97 and 94% respectively, at optimal cutoff, which provided positive and negative predictive values of 85 and 99% respectively, if one considers the prevalence of BA of 25.9% among infants with conjugated hyperbilirubinemia.”

My take: More work is needed.  However, these values suggest that MMP-7 and GGT combined may be more accurate than a liver biopsy in the diagnosis of BA.

Related blog posts:

South Kaibab Trail, Grand Canyon

More on PPIs and Kidney Disease & Brain Disease

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The most recent information and perspective on proton pump inhibitors and kidney disease:

From AGA: More Data on PPI Use and Kidney Disease

An excerpt:

The most recent study related to PPIs and CKD was a meta-analysis by Wijarnpreecha et al. presented at the American Society of Nephrology annual meeting and published in Digestive Diseases and Sciences. They found that any use of PPIs was associated with a 33 percent relative increase in risk for CKD/ESRD whereas no such risk was seen with H2RAs.

Talking to Your Patients
  1. Inform patients that, while this study does raise some concern about long-term PPI use and the potential contributions to kidney disease, the study does not show that PPI use causes kidney disease. No decisions should be made in haste as a reaction to this study. A brief explanation of the meta-analysis may also be helpful. 
  2. Reassure patients that the benefits of using PPIs often outweigh the possible risks. Let them know that you prescribed a PPI for a clear-cut indication, in the lowest possible dose, and for an appropriate period of time (lowest dose, shortest time). 

From the published abstract:

Results: five studies (three cohort studies and two case-control studies) with 536,902 participants met the eligibility criteria and were included in the meta-analysis. We found that individuals with PPIs use had significantly increased the risk of CKD or ESRD when compared with non-PPIs users (pooled RR of 1.33, 95% CI, 1.18-1.51). There was no publication bias of overall included studies assessed by the funnel plots.

My take: (borrowed from the AGA) This is an association, not proof of a causal relationship. Patients who use PPIs differ at baseline than those who do not. For example, patients who use PPIs are more likely to have diabetes or hypertension than patients who do not use PPIs, and are more likely to use additional nephrotoxic medications. Large retrospective studies are unable to completely adjust for these baseline differences. These differences, rather than PPIs themselves, may explain the observed association.

Related study: DCF Klatte et al. Gastroenterol 2017; 153: 702-10.  In this retrospective analysis with more than 100,000 new PPI users (Swedish cohort), PPI users (compared to H2 blocker users) had an increased risk for doubled levels of creatinine with a HR of 1.26, and an increased risk of end-stage renal disease with HR of 2.40. The risk of chronic kidney disease was increased with higher cumulative PPI exposures.

Related study: Effects of PPI on dementia –recent large study shows no association: H Taipale et al. The American Journal of Gastroenterology(2017) 112, 1802–1808 (2017) doi:10.1038/ajg.2017.196.  (Thanks to Ben Gold for this reference. This study examined more than 70,000 Finnish patients with Alzheimer’s disease (AD) (2005-2011) and 280,000 controls.  Results: PPI use was not associated with risk of AD with 3-year lag window applied between exposure and outcome (adjusted odds ratio (OR) 1.03, 95% confidence interval (CI) 1.00–1.05). Similarly, longer duration of use was not associated with risk of AD (1–3 years of use, adjusted OR 1.01 (95% CI 0.97–1.06); ≥3 years of use adjusted OR 0.99 (95% CI 0.94–1.04)). Higher dose use was not associated with an increased risk (≥1.5 defined daily doses per day, adjusted OR 1.03 (95% CI 0.92–1.14)).

Sunrise over the South Rim at the Grand Canyon