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.

What is an Entrustable Professional Activity?

Posted on July 18, 2015 by gutsandgrowth

It has been said that the difference between a haircut and a coiffure is about $30.

When I was reviewing an article (Rose S, et al. Gastroenterol 2014; 147: 233-42 -thanks to Ben Gold for this reference), the previous joke came to mind. While I’m sure that there has been a lot of hard work to improve the effectiveness of gastroenterology fellowship training, I find the term “entrustable professional activity” (EPA) to be a strange term to define specific goals for educational assessment and competency.

Bottomline: For those in training and for those doing the training, entrustable professional activity is the new buzzword.

Briefly noted -unrelated studies:

Wang H et al. J Pediatr 2015; 166: 1404-9. This study examined 4976 among the “Children of 1997,” a prospective population-representative Chinese birth cohort. They “did not find adiposity [to] be a factor in the development of emotional/behavioral problems in early adolescence” (age 11 years).

Niemi AK, et al. J Pediatr 2015; 166: 1455-61. Treatment of methymalonic academia by liver or combined liver-kidney transplantation. This study identified fourteen transplant recipients; the 6 who had isolated liver transplant underwent transplantation much earlier at an average age of 17 months whereas the mean age for transplantation was 8.2 years. The mean serum MMA dropped from 1648 μmol/L to 305 μmol/L (at four months post-Tx). This level is still 1000-fold elevated but was low enough to eradicate episodes of hyperammonemia. In addition, it was associated with stabilization of neurocognitive development.

The Connection Between Anxiety and Gastroesophageal Reflux Disease

Posted on July 17, 2015 by gutsandgrowth

Why is it that reflux is so much worse during periods of anxiety and depression?

A recent prospective study (Kessing BF et al. Clin Gastroenterol Hepatol 2015; 13: 1089-1095) of 225 consecutive patients with symptoms of gastroesophageal reflux disease (GERD) looks into this issue. All patients underwent ambulatory 24-hour pH-impedance (pH-MII) monitoring and had assessment of anxiety/depression with the Hospital Anxiety and Depression Scale.

GERD was defined by having pathologic acid exposure time and/or positive temporal correlation between the occurrence of symptoms ad reflux episodes. Hypersensitivity to reflux was considered if there was physiologic acid exposure times while having temporal association between reflux episodes and symptoms. Functional heartburn indicated the presence of symptoms with a normal pH-MII.

Key findings:

147 patients had GERD and 78 had functional heartburn; 36 patients were considered hypersensitive to gastroesophageal reflux.
Among patients with GERD (including patients with hypersensitivity), increased anxiety/depression levels were associated with more severe retrosternal pain/burning. However, anxiety/depression were NOT associated with an increased number of reflux episodes or number of symptoms reported on pH-MII.
Patients with functional heartburn had higher levels of anxiety than patients with GERD.

Bottomline: Anxiety is associated with increased GERD symptoms. In addition, anxiety is more prevalent in patients with functional heartburn.

Briefly noted: Review (Lipa S, et al. Clin Gastroenterol Hepatol 2015; 13: 1058-67) of 4 trials with 153 analyzed patients: “Stretta [radiofrequency ablation] for patient with GERD does not produce significant changes, compared with sham therapy, in physiologic parameters, including time spent at pH less than 4, LESP, ability to stop PPIs, or HRQOL.”.

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Cumberland Island

Complications with G-tube Placement

Posted on July 16, 2015 by gutsandgrowth

Two recent studies highlight the risks with gastrostomy tube (G-tube) placement.

McSweeney ME, et al. J Pediatr 2015; 166: 1514-9.
Jacob A, et al. J Pediatr 2015; 166: 1526-8.

The first study, a chart review of 591 patients, identified a 10.5% major complication rate and ~25% complication rate overall. By far the most common complication for both major and minor complications was stoma infections. In this study, the g-tube used was the Corflo PEG tubes using a pull-procedure. Perioperative antibiotics (i.e. cefazolin for 24 hrs) were administered. Exchange of g-tubes (to a skin-level device) took place at 6 months in most patients. Major complications were defined as an unplanned adverse event necessitating additional hospitalization, surgery or interventional procedure.

Key findings:

Cumulative incidence of major complications was 2.4% within 48 hours, 5.8% with 1 month, 9.2% within 6 months, and 14.7% at 12 months post-G-tube placement
Among the 62 patients experiencing major complications, 55 of the 72 were due to infections, 6 were dehiscence of PEG at exchange, 2 were due to granulation needing surgery, 2 were due to colon perforation, and 1 due to pneumoperitoneum. Other major complications included: 1 aborted PEG procedure, 1 post-PEG cardiopulmonary arrest, 3 malfunctioning PEG tubes, and 1 failure to exchange PEG tube for a skin-level device.

Overall, this study shows a fairly high rate of significant complications and that their occurrence was usually not in the immediate post-operative period.

The second study was a prospective study of 183 children undergoing a one-step percutaneous G-tube using the MIC-KEY introducer kit. This one-step button requires insertion of three gastropexy anchors, dilatation of gastrostomy tract, and button measurement. The authors evaluated the safety technique and the learning curve.

Key Findings:

In the first 6-month period, the authors noted a 17% failure rate; this declined to 0-7% in the following 6-month study periods.
The time for placement improved from 21 minutes during the first 6-months to 12 minutes during the sixth 6-month study period
The authors highlighted several advantages: 1. lower peristomal infection rate (10.6% compared to their historical control of 29% with pull-PEG); the PEG avoids need to bypass the oropharynx. 2. One procedure/anesthetic for a skin-level device.
In the article, the results indicate that there are clearly tradeoffs for these advantages: after the initial learning curve, their remained complications in the majority (65%), mostly mild complications which included accidental button removal (35%), gastric heterotopy (24%), and peristomal leakage (15%). Also, 35% of patients returned for a replacement tube before the planned date because of intragastric balloon deflation.
The cost savings with this one-step button were estimated to be 11% lower.

Bottomline: While g-tubes remain important in caring for children with feeding problems, there is not a magic bullet to eliminate complications. Understanding the frequency of these problems and discussing them with families will help them be addressed promptly.

Related blog posts:

Best gastrostomy tube | gutsandgrowth

Resource:

www.feedingtubeawareness.com This site contains a terrific PDF download which explains enteral tubes in an easy to understand style along with good graphics. “What You Need to Know Now, A Parent’s Introduction to Tube Feeding is the guidebook that every parent wished they had when they were first introduced to feeding tubes.”

How High Can You Go with Adalimumab?

Posted on July 15, 2015 by gutsandgrowth

A recent study (Inflamm Bowel Dis 2015; 21: 1047-53) explored the “Efficacy and Safety of Adalimumab 80 mg Weekly in Luminal Crohn’s Disease.”

Methods: Between 2011-2012, 42 adults with active Crohn’s disease, defined by CDAI > 150 and an objective marker of inflammation, had a dose escalation of adalimumab to 80 mg weekly in prospective multi center study.

Objective markers could include CRP >0.5 mg/dL, fecal calprotectin >300 mcg/g, radiologic evidence or endoscopic evidence
Only 4 patients were receiving concomitant immunomodulators (& none were started)
There were no reports of adalimumab drug levels

Findings: At 14 weeks, 33.3% achieved a clinical remission (CDAI <150) and 23 (54.8%) had a clinical response. These patients had associated improvements in CRP. The authors do not report on serious adverse events; all AEs “were consistent with previous experience with this drug.”

Take-home point: The authors do not recommend this approach in routine clinical practice at this time. However, it would seem that some patients with low adalimumab trough levels (and no anti-drug antibodies) may benefit from high doses of adalimumab

Briefly noted:

Fumery M, et al. JPGN 2015; 60: 744-48. This retrospective study identified 27 children who received adalimumab (ADA) after infliximab failure. Though ADA was well-tolerated, 8 (30%) had primary nonresponse to ADA and an additional 5 (26%) had ADA failure by 1 year.

Huang EY, et al. Inflamm Bowel Dis 2015; 21: 963-72. “Exposure to dexamethasone in mice led to substantial shifts in gut microbiota over a 4-week period.” Take-home point: Corticosteroids may have both direct and indirect impacts on the microbiome as one mechanism of influencing disease response

Related blog posts:

Zoo Atlanta

When Will MRI Obviate the Need for a Liver Biopsy in Pediatric NAFLD?

Posted on July 14, 2015 by gutsandgrowth

A recent study (JB Schwimmer et al. Hepatology 2015; 1887-95, editorial Vos MB, pages 1779-80) examines the accuracy of magnetic resonance imaging (MRI) compared with liver histology in children with nonalcoholic fatty liver disease.

This prospective validation study enrolled 174 children with a mean age of 14 years. The MRI estimated the liver proton density fat fraction (PDFF).

Key findings:

Liver MRI-PDFF correlated with steatosis grade; the correlation was particularly strong at high and low end values. Thus, a very low MRI-PDFF was highly likely to predict a steatosis grade 0 or 1 while a very high value corresponded to high steatosis levels.
Liver MRI-PDFF was weaker in children with stage 2-4 fibrosis than in children with no fibrosis

The editorial notes that this study “is one of hundreds now published in the literature on MRI and NAFLD…The superiority of MR-based methods…over ultrasound is clear. The question is why are we still ordering abdominal ultrasounds to diagnose NAFLD in children?” The barriers for usage of MRI include cost, potential sedation, and nonuniform methods for MRI usage.

The paper conclude that “MRI is not yet sufficient to replace liver biopsy in children.” The editorial also indicates that the MRI era is fast approaching but not viable today.

Take-home point: Due to the huge numbers of patients with pediatric NAFLD, MRI remains a terrific area for research but remains problematic in clinical practice. Given the expense of MRI, until its use can reduce liver biopsies or improve management, its role is likely to remain limited.

Turner Field

Genetically Modified Humans: Genome Editing 101

Posted on July 13, 2015 by gutsandgrowth

In a review at last year’s NASPGHAN meeting, John Barnard gave a basic science review (Basic Science Year in Review -#NASPGHAN 2014 | gutsandgrowth) that touched on CRISPR-Cas9 for genome engineering (Cell 2014; 157: 1262-78). Reading through a recent editorial (Lander ES. NEJM 2015; 373: 5-7), it seems that the potential for genome editing is not that far from landing into clinical use.

His points:

Genome editing holds great therapeutic promise…

“physicians might edit a patient’s immune cells to delete the CCR5 gene, conferring the resistance to HIV carried by the 1% of the U.S. population.”
“Editing blood stem cells might cure sickle cell anemia and hemophilia.”
Eliminate genes which increase the risk for Alzheimer’s, Huntingdon’s disease and heart attacks

Concerns:

“Genetically modified humans” and true “designer babies”
Technical issues to perform editing with precision.
Unanticipated effects with various edits. “We remain terrible at predicting the consequences of even simple genetic modification.”
Who decides? Future generations cannot consent to their modification.
Is it morally right? “Would the ‘best’ genomes go to the most privileged?”

In the U.S., genome editing would not garner approval from FDA or NIH in the near future. But, given the advancing technical capabilities, it is not too early to begin the discussion about genome editing. At the very least, this technology should spurn a couple great sci-fi movies.

Take-home point: “Authorizing scientists to make permanent changes to the DNA of our species is a decision that should require broad societal understanding and consent…We should exercise great caution before we rewrite” the human genome.

Zoo Atlanta (Kinda looks like a genetically-modified giraffe)

Not Thirsty for Water

Posted on July 12, 2015 by gutsandgrowth

As noted in several previous posts (see below), many kids (and adults) would likely benefit from increased water consumption. The pervasiveness of this problem was recently discussed in a recent (June 11th) USA Today article (“Researchers to kids: drink more water”), though experts disagree on whether mild water deficits are detrimental.

Here’s an excerpt:

The study, published Thursday by the American Journal of Public Health, found 54.5% of children ages 6 to 19 inadequately hydrated, at least by the standard set in the study.

The findings, based on one-time urine samples from more than 4,000 children, do not mean most children are seriously dehydrated…

The researchers considered a child inadequately hydrated if the concentration reached a level other studies have linked to sluggish thinking and mood changes.

They found boys and black children were more likely than girls and children of other races to have highly concentrated urine…

But … some experts …say most people can judge their fluid needs by thirst alone – and that fluids can come from any drink and many foods…

The study showed 22% of children drank no water.

Related blog posts:

Will Infliximab Worsen Flare-ups Associated with Cytomegalovirus Infection?

Posted on July 11, 2015 by gutsandgrowth

Another look (Pillet S, et al. Inflamm Bowel Dis 2015; 21: 1580-86) at Cytomegalovirus (CMV) infection in patients with ulcerative colitis (UC) examines 109 flareups in 73 patients who were receiving maintenance therapy with anti-TNF therapy.

This was a single-center prospective observational study. CMV load was determined with PCR based on a pair of biopsies. DNA load was either undetectable, mild (10-250 copies/mg of tissue) or high (>250 copies/mg of tissue). 69 patients with anti-TNF therapy were compared with 40 patients receiving azathioprine. Key findings:

CMV reactivation was noted in 35% of anti-TNF therapy patients and 38% in azathioprine patients.
Among 45 patients requiring infliximab optimization, clinical remission was not significantly impacted by the presence of CMV reactivation.
17 of 20 who had repeat biopsies 8 weeks later had stable or decreased CMV load.

Bottomline: This prospective, small study shows that “in patients with moderate-to-severe UC, treatment with anti-TNF mab does not increase the risk of colonic CMV infection.” In addition, “no adverse influence of CMV colonic infection was observed in patients with flare-up treated by anti-TNF mabs.”

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.

Zoo Atlanta

Utility of Antiviral Therapy for Cytomegalovirus in the Setting of Inflammatory Bowel Disease

Posted on July 10, 2015 by gutsandgrowth

According to a recent study (Jones A et al. Clin Gastroenterol Hepatol 2015; 13: 949-55), the tissue density of cytomegalovirus (CMV) is an important determinant of antiviral response in patients with inflammatory bowel disease (IBD).

In this case-control study, the authors identified 68 samples from 1111 patients with IBD that were found to contain CMV. Adequate data was available for 50, including 16 with high-grade CMV (all treated) and 34 with low-grade CMV (20 treated). High-grade CMV was defined as biopsies with 5 or more inclusions. Treatment included ganciclovir, valganciclovir or both; 33 of 36 treated patients received at least 21 days of therapy.

Key findings:

Patients with high-grade CMV showed significant benefit from treatment: they had the best outcomes with “only 33% undergoing surgery by 1 year after biopsy.”
All patients with low-grade CMV, treated or not, were more likely to undergo surgery than those with high-grade CMV, with HR of 2.13. However, the treated low-grade CMV had a lower risk of surgery (HR 0.39) compared with the untreated group. 73% of the untreated low-grade CMV group had undergone resection by 1 year after biopsy.

The authors note the many limitations of the study. Requests to rule out CMV were not done uniformly but “usually reflected refractoriness of steroids or failure to respond to escalation of therapy.”

Bottomline: In those with high-grade CMV, the likelihood of responding to antiviral therapy was much higher than in patients with low-grade CMV; however, treatment in all patients with CMV inclusions was associated with improved outcomes.

Another Way of Preventing Recurrent Clostridium Difficile

Posted on July 9, 2015 by gutsandgrowth

I frequently tell families that Clostridium difficile is the ‘Forrest Gump’ of bacteria; it tends to do well when its competitors are decimated. One of the problems with Clostridium difficile infection (CDI) has been recurrence. This occurs in part because after treatment of CDI the microbiota of the host remains vulnerable to recurrence. This has been one of the rationales behind the use of probiotics. However, probiotics have not been very effective. As such, more research has been directed in this area. This includes a recent study (Gerding DN et al. JAMA 2015; 313: 1719-27) which showed that administration of spores of nontoxigenic Clostridium difficile can prevent recurrent CDI.

While fecal microbiota transplantation (FMT) has been very effective in treating CDI, there is definitely a yuck factor. In addition, more targeted therapy is desirable. In this study, the authors enrolled 173 patients (157 completed treatment) at 44 study centers as part of a phase 2, randomized, double-blind placebo-controlled, dose-ranging study. After completion of antibiotics (metronidazole or vancomycin), participants received 1 of 4 treatments with a nontoxigenic C difficile strain M3 (NTCD-M3).

Key findings:

Recurrence of CDI were reported in 14 (11%) of NTCD-M3 patients compared with 13 (30%) placebo patients.
69% of NTCD-M3 patients were colonized. Recurrence in this group (n=86) occurred in 2 (2%) compared with 12 (31%) of NTCD-M3 non-colonized patients.
Fewer adverse events were noted in NTCD-M3 group compared with placebo patients with serious events occurring in 3% and 7% respectively.

Bottomline: These nontoxigenic oral spores of NCTD-M3 were well-tolerated and significantly reduced the risk of recurrent CDI.

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