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.

Isopropyl Alcohol -Antiemetic Aromatherapy

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April MD et al. Aromatherapy versus oral ondansetron for antiemetic therapy among adult emergency department patients: A randomized controlled trial. Ann Emerg Med 2018 Feb 17; [e-pub]. (https://doi.org/10.1016/j.annemergmed.2018.01.016) Thanks to Ann Beach for this reference.

Review/excerpt of this study from NEJM Journal Watch: by Daniel J. Pallin, MD, MPH.

In the current trial, 120 adult ED patients with nausea or vomiting who did not require intravenous access were randomized to inhaled isopropyl alcohol plus 4 mg oral ondansetron; inhaled isopropyl alcohol plus oral placebo; or inhaled saline plus 4 mg oral ondansetron. Isopropyl alcohol was provided in the form of a standard alcohol swab. Patients received a single dose of the oral intervention but could sniff alcohol or saline swabs repeatedly. Nausea was measured on a 100-mm visual analog scale at baseline and 30 minutes.

Mean nausea scores decreased by 30 mm in the alcohol/ondansetron group, 32 mm in the alcohol/placebo group, and 9 mm in the saline/ondansetron group. Rescue antiemetic therapy was given to 28%, 25%, and 45% of each group, respectively. Differences between alcohol and saline groups were statistically significant. Patients in the inhaled alcohol groups also had better nausea control at the time of discharge and reported higher satisfaction with nausea treatment. No adverse events occurred. The mechanism of action is currently unknown.

Dr. Pallin’s comments on study:

It is uncommon for us to assign a rating of “Practice Changing” to a small, single-center study, but these results are truly remarkable and are consistent with prior research. For patients not obviously requiring IV therapy, we should treat nausea with repeated inhalations from an isopropyl alcohol swab instead of administering any other drug. And, although this study provides no direct evidence of benefit to patients who do require IV therapy, there would seem to be little downside to trying this simple and safe intervention in that group, too.

My take: Who is doing the pediatric study to try to replicate these results in the pediatric population?

Related blog posts:

Foggy Morning in Sandy Springs

How to Cultivate Clostridium difficile Infections

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The emergence of more frequent and virulent Clostridium difficile infections (CDIs) has generally been attributed to antibiotic usage.  A recent study (J Collins et al Nature 553, 291–4.  doi:10.1038/nature25178) suggests that changes in our diet are a contributing factor as well.

From Abstract:

Here we show that two epidemic ribotypes (RT027 and RT078) have acquired unique mechanisms to metabolize low concentrations of the disaccharide trehalose. RT027 strains contain a single point mutation in the trehalose repressor that increases the sensitivity of this ribotype to trehalose by more than 500-fold. Furthermore, dietary trehalose increases the virulence of a RT027 strain in a mouse model of infection. RT078 strains acquired a cluster of four genes involved in trehalose metabolism, including a PTS permease that is both necessary and sufficient for growth on low concentrations of trehalose. We propose that the implementation of trehalose as a food additive into the human diet, shortly before the emergence of these two epidemic lineages, helped select for their emergence and contributed to hypervirulence.

From GI & Hepatology News: Food additive makes C difficile more virulent: “Prior to 2000, trehalose was limited by a relatively high cost of production.”  However, with innovations in production, trehalose concentrations in food increased, particularly in ice cream, pasta, and ground beef; “concentration in food skyrocketed form around 2% to 11.25%.”  In addition, the FDA in 2000 noted that trehalose as “generally recognized as safe.”

My take: “On the basis of these observations, we propose that the widespread adoption and use of the disaccharide trehalose in the human diet has played a significant role in the emergence of these epidemic and hypervirulent strains,” Dr. Collins and his colleagues wrote in Nature.

Flower Display in Las Vegas Hotel

March for Our Lives

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Today there is a “March for Our Lives”

Some relevant tweets:

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For the Next Upper GI Bleed, Azithromycin?

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Earlier this week, I was tasked with helping a teenager with an upper GI bleed.  I was surprised to learn that our hospital did not have IV erythromycin available due to a shortage.  A potential alternative is azithromycin.

The following is a 2017 ACG abstract (D Issa et al): A Comparison of Azithromycin to Erythromycin Infusions in Improving Visualization of Endoscopy for Upper Gastrointestinal Bleeding

Introduction: Several studies show the use of intravenous erythromycin prior to upper endoscopy for upper gastrointestinal bleeding (GIB) improves visualization and decreases the need for second look endoscopy. Erythromycin requires reconstitution delaying administration in emergency procedures. Azithromycin is more readily available as it is part of pneumonia treatment protocols and does not require reconstitution. Physiologic studies show azithromycin produces motility effects similar to that of erythromycin.

Aim: To assess the effect of azithromycin in improving the quality of endoscopic visualization in upper GIB compared to erythromycin.

Methods: We performed a retrospective analysis of patients admitted with acute upper GIB who underwent emergent endoscopy and were ordered either erythromycin or azithromycin before procedure. Primary outcome of the quality of visualization was assessed by two gastroenterologists, blinded to the choice of infusion, using a scoring system ranging from 0 to 8 with a maximum of 2 points assigned to each of the fundus, body, antrum and bulb. Secondary outcomes included time elapsed between administering the infusion and starting the procedure, length of hospital stay, blood transfusions, and procedure-related complications.

Results: The study included 31 patients in the erythromycin group and 18 patients in the azithromycin group. Mean age was 57 years and 68% were male. The overall median visualization score was significantly higher in the azithromycin group compared to that of the erythromycin group {7.0 (1.5) vs. 6.0 (3.0), respectively; P=0.02}. Time between administration of azithromycin and starting the procedure was longer than that of erythromycin but did not meet statistical significance (67 vs 48.5 minutes, respectively; P = 0.92). Length of hospital stay was comparable between the two groups after adjusting for the admission primary diagnosis (6.0 days for azithromycin vs. 7.0 days for erythromycin; P=0.48). Four patients were ordered erythromycin but this was not administered on time whereas all patient who were ordered azithromycin started the infusion prior to the procedure. Procedure immediate complications, need for second look endoscopy and number of transfused blood units did not differ between the groups.

Discussion: Azithromycin infusion before endoscopy for upper GIB was associated with better visualization than that of erythromycin, the current standard of care. Randomized trials are needed to validate these findings.

Here is a link to a summary from Gastro and Endoscopy News: Azithromycin Appears Worthy Stand-In For Erythromycin in Upper GI Bleeding

There have been prior publications showing that azithromycin, like erythromycin, has prokinetic properties: Broad J, Sanger GJ. The antibiotic azithromycin is a motilin receptor agonist in human stomach: comparison with erythromycin. Br J Pharmacol. 2013 Apr;168(8):1859-67.

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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.

Motility in Duchenne Muscular Dystrophy

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Briefly noted: D Kraus et al J Pediatr 2018; 194: 238-40.  This study of 7 young adults with Duchenne muscular dystrophy (DMD_ showed normal gastrointestinal motility using a wireless motility capsule (WMC).  The study findings are limited by the small sample size and a selection bias of enrolling only patients capable of swallowing a WMC. This study, however, is important as it supports the notion of ‘enteric muscle sparing’ in DMD.

Related blog post: Don’t Let the Chief of Staff Review This Study

Chattahoochee River

IBD Shorts -March 2018

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T Piester et al. Inflamm Bowel Dis 2018; 24: 227-34.  Stanford group published data on 49 patients which highlight the utility of a point of care (mobile) infliximab (IFX) dosing calculator: http://med.stanford.edu/gastroenterology/infliximab-calc/  In their cohort, the IFX calculator recommendations were for IFX dosing escalations in 13% of the 222 calculations.  Overall, the IFX calculator was part of a larger quality initiative (QI) to achieve therapeutic drug levels >5 mcg/mL which occurred in 81% during the QI period.

JC deBruyn et al. JPGN 2018; 66: 268-77. This was a retrospective review of infliximab (IFX) in pediatric Crohn’s disease with 180 children. The authors determined that IFX had good therapeutic durability with 91% remaining on IFX after 2 years of treatment.

FS Macaluso et al. Inflamm Bowel Dis 2018; 24: 394-401. In this 2-year study, among 630 patients, 46 had a modestly-dosed immunomodulator added to anti-TNF therapy due to loss of response (31 to IFX or biosimilar, 10 with adalimumab, and 5 with golimumab).  This resulted in a steroid-free remission in 15 (32.6%) and a clinical response in 6 (13.0%). The immunomodulators were azathioprine in 15, 6-mercaptopurine in 5, methotrexate in 20, and mycophenolate mofetil in 6. The median doses for immunomodulators were 1.64 mg/kg/day, 0.84 mg/kg/day, 15.6 mg/week, and 1500 mg/day respectively.

C Reenaers et al. Clin Gastroenter Hepatol 2018; 16: 234-43. This retrospective study examined 7-year outcomes from a STORI cohort of 115 adults with Crohn’s disease (CD) with combination therapy who had infliximab withdrawal after achieving sustained remission. Among those restarting infliximab, treatment failed in 30.1%; 70.2% “had no failure of de-escalation strategy.” Major complicatins occurred in 18.5% of patients. Risk factors for failure included anemia (Hgb <12.5), increased white blood cell count >5.0, and upper GI location of CD.

VM Merrick et al. JPGN 2018; 66: 274-80.  This UK “real-life” review of 37 centers and 524 patients (429 with Crohn’s disease) found a remarkably poor rate of documentation.  They could determine the remission rates in only 71 of these patients (65% 46 of 71).  Thus, in the real-world, presumably in adults and children, most institutions do not know their remission rates.  While the determination of remission still relies on imperfect measures, the centers who participate in ImproveCareNow have high documentation rates –this is also a real-world experience as more than 29,000 patients and more than 900 pediatric GI doctors participate.

Esophageal Diseases Special

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Gastroenterology published a ‘special issue’ in January 2018 (volume 154; pages 263-451) which reviewed several esophageal diseases in-depth: gastroesophageal reflux disease (GERD), eosinophilic esophagitis (EoE), and esophageal cancer. For me, this issue served as a good review on GERD and EoE.

A couple of items that I picked up:

  • For both GERD and functional dyspepsia, “estimated prevalence values are approximately 20% for each.” (pg 269)
  • “15% of healthy individuals may have microscopic esophagitis” (pg 291)
  • For pH-impedance, the current view of non-acid reflux is unchanged: “unknown clinical relevance of non-acid reflux in the setting of aggressive acid suppression.” (pg 291)
  • Treatment algorithm for EoE (pg 353):
    • Induction treatment with any of the three approaches:  high dose topical corticosteroids, double dose proton pump inhibitor (PPI) or elimination diet “because no comparative studies have shown any of these to be superior to the others.”
    • Then, re-evaluation after 2-3 months (clinical, endoscopic, and histologic).  Responders should continue on therapy but maintenance treatment suggests low dose topical corticosteroid, lowering PPI to single dose, or continuing elimination diet.  For nonresponders, switching to one of the other two treatment approaches is recommended.
    • The algorithm indicates that followup evaluation of responders to insure ongoing response should be considered 1 year later
  • As for dilatation, the authors note that this does not control the underlying inflammation and thus should not be used as monotherapy. Also, “after dilatation, 75% of patients have considerable chest pain that may last several days.” (pg 354)

Unrelated twitter post below -IgG allergy testing is NOT a good idea:

Cost Effective Fecal Transplantation

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A recent retrospective study (DE Brumbaugh et al. J Pediatr 2018; 194: 123-7) examined the effectiveness of intragastric fecal microbiota transplantation (FMT) for recurrent Clostridium difficile infection (CDI) in 42 children (47 FMTs).

Key findings:

  • 94% (16/17) success in otherwise healthy children
  • 75%  (9/12) success in medically complex children
  • 54% (7/13) success in inflammatory bowel disease.
  • Figure 2 describes cost: nasogastric FMT cost for hospital/professional charges was $1139 compared to $4998 for nasoduodenal FMT and $7767 for colonoscopy FMT

To understand the results better, one needs to look at their methods.  The authors defined CDI based on a positive fecal polymerase chain reaction (PCR) test.  All patients undergoing FMT had to have had >2 episodes of CDI.

The authors discuss the issue that asymptomatic Clostridium difficile carriage is common in IBD (“6 times that in healthy controls”) and the fact that true CDI can be difficult to ascertain as the relative contribution of IBD activity can be difficult to separate from CDI.  Interestingly, the authors did not comment on their use of PCR testing to establish infection.

As noted in a previous blog post (Overdiagnosis of Clostridium difficile with PCR assays), immunoassay testing for toxin is likely helpful in equivocal cases.  In an influential JAMA Intern Med study (JAMA Intern Med. 2015;175(11):1792-1801.  doi:10.1001/jamainternmed.2015.4114), virtually all CDI-related complications and deaths occurred in patients with positive toxin immunoassay test results. Patients with a positive molecular test result and a negative toxin immunoassay test result had outcomes that were comparable to patients without C difficile by either method.

Other useful points in this study:

  • The authors note that craniofacial anatomy may preclude NG placement in some patients (in some orogastric insertion could be an alternative)
  • Patients at high risk for GERD/aspiration along with general anesthesia patients are “not good candidates for FMT”
  • “If there is concern for undiagnosed IBD or other GI pathology, FMT via colonoscopy may be preferable” as FMT could be diagnostic and therapeutic.

My take: This study confirms the utility of intragastric FMT for recurrent CDI as a cost-effective option.  More careful examination of CDI in patients with IBD could result in determining which patients are most likely to benefit from FMT

Hoover Dam

 

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What Should an Aerodigestive Program Look Like

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A recent “consensus statement” publication (Boesch RP, et al. Pediatrics 2018; 141: e20171701) discusses the structure and functions of an aerodigestive program. Congratulations to Dr. Ben Gold –one of my partners and a coauthor.

Overall this is a useful document and a good starting point to establish what an aerodigestive program should look like.

  • Table 1 lists common conditions addressed by aerodigestive programs like chronic cough, Gtube dependence, failure to thrive, TEF/esophageal atresia, recurrent infections, craniofacial anomalices, tracheostomy dependence, vocal cord dysfunction, stridor and wheezing.
  • Table 2 lists important team members.
  • Table 3 establishes important functions like care coordination, combined endoscopy, and summary of recommendations.
  • Table 4, 5, and 6 summarizes procedural skills needed by pulmonology, gastroenterology, and ENT respectively.

The accepted definition of an aerodigestive disorder: “A pediatric aerodigestive patient is a child with a combination of multiple and interrelated congenital and/or acquired conditions affecting airway, breathing, feeding, swallowing, or growth that require a coordinated interdisciplinary diagnostic and therapeutic approach to achieve optimal outcomes.”

  • The authors were split on whether the care needs to be provided by all providers in the same space or whether coordination can occur with separate physician locations.
  • The authors argue that coordinated care is valuable, citing care in children with cystic fibrosis and inflammatory bowel disease (via ImproveCareNow).
  • They note the major limitation is that their recommendations are based on expert opinion.

My take: My main concerns with multidisciplinary care, having participated in a number of multidisciplinary teams, are the following:

  1. There is a lot of redundancy in care with these clinics.  Often, these clinics result in a patient having two GIs, two pulmonologists, and two ENTs. If the aerodigestive team is useful, the aerodigestive expertise needs to be substantially greater than the expertise of their colleagues.  If it is simply a matter of care coordination, this is a deficiency that could be corrected in the absence of a multidisciplinary team.
  2. Many patients do not need all of the multidisciplinary team members. This increases costs unnecessarily.
  3. The potential promise of care coordination is sometimes offset by the extremely lengthy visits at multidisciplinary visits.

So in my view, the key for aerodigestive clinic success is to identify a narrow population of children with high-complexity problems and to identify subspecialists with exceptional abilities.  As an aside, the study states that Cincinnati was the first location to establish a pediatric aerodigestive clinic.  The success there was in large part due to Dr. Colin Rudolph (GI) and Dr. Robin Cotton (ENT), both recognized leaders and innovators in their fields.

Tunnels and hallways inside Hoover Dam