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.

Why Does this Patient Have Colitis?

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Just in time for this year’s Peachtree Road Race…

A brief report (RS Robinson et al. Gastroenterol 2018; 154: 1582-83) presents a case of a 28 year old, who had been in training for a marathon, with mild iron deficiency anemia, lower abdominal pain, and bloody bowel movements. The CT scan and colonoscopy showed diffuse colonic/ileal inflammation; the histology showed mucosal necrosis, crypt atrophy and acute inflammation (see below).

Answer to title question: Runner’s Colitis.  The authors note that in some long-distance runners an ischemic colitis can develop in part due to rerouting of blood with prolonged exercise.  Dehydration may exacerbate poor perfusion.  The splenic flexure and the rectosigmoid junction are particularly susceptible due to the ‘watershed’ nature of their blood supply.

The majority of individuals recover fully from this insult, though the literature describes one individual who required a subtotal colectomy after perforation.

HCV Treatment and “MELD Purgatory”

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A recent study (A Kwong et al. Liver Transplantation 2018; 24: 735-43) and associated editorial (P Martin, pg 727-8) highlight an unintended consequence of HCV therapeutic success –“MELD purgatory.”

The study notes that with the availability of more effective direct-acting antivirals for HCV, there has been a decrease in wait-list mortality and a decrease in disease severity.  This was determined by reviewing 3 timed cohorts (2004 n=2408, 2009 n=2402, and 2014 n=2817) from the Organ Procurement and Transplantation database.

  • For example, the 2014 had a 21% lower risk of wait-list death (HR 0.79) than the 2009 cohort.  This is in contrast to other (non-HCV) disease in which there was no change in mortality.
  • Also, the MELD rate of change was 2.35 per year for the 2009 cohort compared to 1.90 for the 2014 group.
  • In their discussion, the authors note that while patients with HCV can achieve a sustained virologic response, those with advanced liver disease still need liver transplantation.  In these patient, there is a much lower prospect of attaining a high enough MELD score to receive organ offers –“leaving them with persistent complications and a decreased quality of life.”  This situation has been termed “MELD purgatory.”

The editorial notes that in the five years since the introduction of sofosbuvir, HCV has been displaced as the single commonest indication for liver transplantation by nonalcoholic fatty liver disease.  These agents have led to a decrease in advance HCV-related liver disease.  In addition, in the past, HCV infection had near universal recurrence after transplantation and this is no longer the situation.

My take: Undeniably, the advent of DAA have made a huge dent in progressive HCV liver disease. However, those with advanced liver disease may be stuck in a purgatory between good health and poor quality of life even after clearance of HCV infection.

Related blog posts:

VICTORY Consortium Showing Good Results for Vedolizumab

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A presentation at the 13th Congress of the European Crohn’s and Colitis Organization (ECCO, Feb 2018) indicated that Vedolizumab had similar effectiveness as anti-TNF agents for both ulcerative colitis and Crohn’s disease. This data has been presented at a recent meeting in our office, some of the GI news magazines, and also ImproveCareNow listserv.

From Takeda website: Entyvio® (vedolizumab) Shows Higher Rates of Mucosal Healing Versus TNFα-Antagonist Therapy in Ulcerative Colitis and Crohn’s Disease Patients in Comparative Effectiveness Real-World Data Analysis

These analyses observed that patients with UC treated with Entyvio compared to TNFα-antagonist therapy had statistically significant higher 12-month cumulative rates of mucosal healing (50% vs 42%, hazard ratio [HR] 1.73, 95% confidence interval [CI] 1.10‑2.73) and clinical remission (54% vs 37%; HR 1.54, 95% CI 1.08‑2.18), and numerically higher steroid-free clinical remission rates (49% vs 38%; HR 1.43, 95% CI 0.79‑2.60). In CD, results reported statistically significant higher 12-month cumulative rates of mucosal healing (50% vs 41%; HR 1.67, 95% CI 1.13‑2.47), and numerically higher rates of clinical remission (38% vs 34%; HR 1.27, 95% CI 0.91‑1.78) and steroid-free clinical remission (26% vs 18%; HR 1.75, 95% CI 0.90‑3.43) compared to TNFα-antagonist therapy. These analyses were conducted by the VICTORY (Vedolizumab Health OuTComes in InflammatORY Bowel Diseases) Consortium.

My take: While the data compare anti-TNFs to vedolizumab in a “real-world setting,” the reported outcomes for anti-TNFs are lower than in other studies.  Vedolizumab had the best results in those with colonic disease.  Patients with Crohn’s disease with isolated small bowel disease had lower response rates.

Related study: AK Waljee et al Inflamm Bowel Dis 2018; 24: 1185-95. Using phase 3 clinical trial data with 594 subjects, the authors note that the majority of patients who will respond to vedolizumab can be identified by week 6 using a laboratory algorithm based on hemoglobin, albumin, vedolizumab level and CRP. Fformula: Hgb*Albumin*VDZ level/CRP*Weight. A cutoff of 185.96 predicted success with an AuROC of 0.75.   Higher hemoglobin, higher albumin, and higher vedolizumab level, and lower CRP are associate with higher response rates.

Related blog posts:

Red Top Mountain, Homestead Trail

 

 

 

What to Make of Median Arcuate Ligament Syndrome

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A recent study (C Stiles-Shields et al. JPGN 2018; 66: 71) reports on 32 cases of median arcuate ligament syndrome (MALS) from a single center, 2011-17.  To me, this is an astounding number of individuals who were operated on for this disorder.  As the authors note, “MALS remains a controversial and vexing condition. 13% to 50% of healthy patients may exhibit radiographic features of celiac artery compression.”

While the authors note that pain symptoms improved significantly, they report that “comorbid psychological conditions were common, occurring in about half the sample before and after surgery.”

My take: If one finds celiac artery compression and suspects MALS, it is unclear to me if an operation is indicated and how to determine when it is indicated.

Related blog post:

Proctor Creek Trail

Which Proton Pump Inhibitor is the Most Potent?

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A recent study (DY Graham, A Tansel. Clin Gastroenterol Hepatol 2018; 16: 800-808) analyzed 56 randomized trials to determine relative potency of proton pump inhibitors (PPIs) based on time in which intragastric pH was 4 or less (pH4time).

Key findings:

  • Pantoprazole 20 mg was equivalent to 4.5 mg of omeprazole
  • Lansoprazole 15 mg was equivalent to 13.5 mg of omeprazole
  • Esomeprazole 20 mg was equivalent to 32 mg of omeprazole
  • Rabeprazole 20 mg was equivalent to 36 mg of omeprazole

The authors note that peak effectiveness for PPIs was at ‘approximately 70 mg of omeprazole equivalents’.  In addition, they state that twice a day dosing was more effective than increasing once a day dosing; however, three times a day dosing was not more effective than twice a day. “Dexlansoprazole, a quasi-twice-a-day formulation produced similar acid suppression to the lowest twice-daily PPI regimen and 20 mg vonoprazan once daily provided similar efficacy aas high-dose twice-daily PPI.” The authors also compare costs; generics of pantoprazole, omeprazole, and esomeprazole cost as little as $0.02-0.04 per omeprazole equivalent.  Thus, 20 mg of omeprazole would be as little as 40 cents.

My take: Using the lowest effective dose of a PPI is recommended.  In patients needing higher dosing or with suboptimal response to acid suppression, this data can be very helpful.

 

Proctor Creek Trail

The Risk of Pancreatic Cancer After Acute Pancreatitis

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A recent study (J Kirkegard et al. Gastroenterol 2018; 154: 1729-36) determined that acute pancreatitis is associated with an increased risk of pancreatic cancer. This finding is based on a nationwide (Denmark), matched cohort study of all patients admitted with acute pancreatitis from 1980 to 2012.  This involved 41,669 patients with acute pancreatitis and 208,340 comparison subjects.

Key finding:

  • Five year pancreatic cancer risk was 0.87% compared to a risk of 0.13% in the comparison group (HR 2.02)

Limitations: While this study is based on a Danish registry, the authors note that the data had been prospectively entered and has a high validitiy.

My take: While I have not seen pancreatic cancer in the pediatric population, it is concerning that episodes of pancreatitis are likely to increase this risk for the children as well (over their lifetimes).

Mountain Laurel (?) -Pine Mountain Trail

How to Identify Dubin-Johnson Syndrome

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Typically, most pediatric gastroenterologists want to remember that the gross appearance of the liver in patients with Dubin-Johnson is black as this is rumored to be a frequently asked question for board testing.  Practically, though other features are important to recognize since the color of the liver is not readily evident except during surgery.  As such, a recent retrospective study (T Togawa et al. J Pediatr 2018; 196: 161-7) describes 10 neonatal patients from Japan.

Key findings:

  • Only 3 of the 8 patients who underwent liver biopsy had a grossly black liver
  • All liver specimens showed no expression of multidrug resistance-associated protein 2 and increased expression of the bile salt export pump protein
  • Homozygous or compound heterozygous pathogenic variants of ABCC2/MRP2 (ATP-binding cassette subfamily C member 2/multidrug resistance-associated protein 2) were identified in all patients

The clinical course was similar in the patients:

  • Cholestasis self-limited/benign: “severe cholestasis developed in the neonatal period…reaching a maximum at 19 to 60 days. Cholestasis then decreased and disappeared at 2 to 9 months of age.”  Acholic stools were common during the cholestatic phase.
  • Serum AST and ALT remained consistently normal
  • There was no hepatosplenomegaly and no failure to thrive

My take: Dubin-Johnson syndrome is much easier to identify with the availability of genetic panels.

Related blog post: Dubin-Johnson Syndrome

 

Hereditary Fructose Intolerance

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A recent case series (Li H, A Diaz-Kuan, M Vos et al. Mol Genet Metab. 2018 Apr;123(4):428-432) highlights the importance of dietary history in infants with liver failure (abstract below).  Congratulations to my colleague Miriam Vos one of the coauthors.

Commentary on this publication from Emory News (from Kipp Ellsworth’s twitter feed):

Babies with inherited intolerance of fructose face a risk of acute liver failure if they are fed certain widely available formulas containing fructose, pediatricians and geneticists are warning. Baby formula manufacturers should remove fructose or sucrose, or explicitly label their products to allow parents to avoid those sweeteners if necessary, the doctors say.

In a recent paper in Molecular Genetics and Metabolism, Emory geneticists Hong Li, MD, PhD and Michael Gambello, MD, PhD together with Children’s Healthcare of Atlanta pediatric hepatologist Miriam Vos, MD and colleagues report four cases of hereditary fructose intolerance (HFI), all diagnosed in early infants. All had acute liver failure that resolved when the infants switched to formula without fructose.

HFI is estimated to occur in 1 out of 20,000 live births. It comes from mutations in the aldolase B gene, resulting in an inability to metabolize fructose. Early symptoms include nausea, vomiting, abdominal pain and failure of an infant to gain weight. If unrecognized, HFI can result in liver and kidney damage, seizures or death.

HFI-related problems do not appear if an infant is being breastfed exclusively. It is normally recognized when fructose-containing solid foods, such as fruit, are introduced into the diet several months after birth. However, some baby formulas – often soy-based – contain sweeteners such as high-fructose corn syrup or sucrose (table sugar), which is made of fructose and glucose linked together. Sometimes, the label only says “sugar” instead of sucrose…

Since HFI is a treatable disease, Li urges pediatricians to consider HFI as a potential diagnosis if there is a feeding problem, elevated transaminase enzymes or jaundice (a sign of liver damage) and the infant has been fed formula containing fructose or sucrose.

Some information about a young patient’s condition can be obtained from urine carbohydrate tests, but the only way to confirm HFI is by genetic sequencing.

Abstract:

Hereditary fructose intolerance (HFI) is an autosomal recessive disorder caused by aldolase B (ALDOB) deficiency resulting in an inability to metabolize fructose. The toxic accumulation of intermediate fructose-1-phosphate causes multiple metabolic disturbances, including postprandial hypoglycemia, lactic acidosis, electrolyte disturbance, and liver/kidney dysfunction. The clinical presentation varies depending on the age of exposure and the load of fructose. Some common infant formulas contain fructose in various forms, such as sucrose, a disaccharide of fructose and glucose. Exposure to formula containing fructogenic compounds is an important, but often overlooked trigger for severe metabolic disturbances in HFI. Here we report four neonates with undiagnosed HFI, all caused by the common, homozygous mutation c.448G>C (p.A150P) in ALDOB, who developed life-threatening acute liver failure due to fructose-containing formulas. These cases underscore the importance of dietary history and consideration of HFI in cases of neonatal or infantile acute liver failure for prompt diagnosis and treatment of HFI.

Related blog post: Changing Approach to Neonatal Acute Liver Failure

Chattahoochee River Near Island Ford