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.

Big Advance for Hepatitis B, Plus One

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A recent open-label randomized controlled study (M Bazinet et al. Gastroenterol 2020; 158: 2180-94.  https://doi.org/10.1053/j.gastro.2020.02.058) showed that the addition of nucleic acid polymers (NAPs) which inhibit assembly and secretion of hepatitis B virus (HBV) subviral particles significantly improved outcomes in a phase 2 HBV trial (n=40).

Full text: Safety and Efficacy of 48 Weeks REP 2139 or REP 2165, Tenofovir Disoproxil, and Pegylated Interferon Alfa-2a in Patients With Chronic HBV Infection Naïve to Nucleos(t)ide Therapy

NAP therapy was administered intravenously once a week.

Key findings:

  • During the first 24 weeks of tenofovir (TDF) and peg-Interferon (pegIFN) administration, significantly higher proportions of patients in NAP groups had decreases in HBsAg to below 1 IU/mL (P < .001 vs control) and HBsAg seroconversion (P = .046 vs control).
  • At the time patients completed the TDF + pegIFN + NAP regimen, HBsAg levels were 0.05 IU/mL or lower in 24/40 participants
  • During 48 weeks of treatment-free follow-up, virologic control persisted in 13 of 40 participants (2 lost to follow-up after 24 weeks), whereas functional cure persisted in 14 of 40 participants (all completing 48 weeks of follow-up) with persistent HBsAg seroconversion

The associated editorial (pg 2051-4 by D Durantel, T Asselah) makes the following points:

  • The authors call for larger multicenter studies with longer followup.  They note that more evaluation is needed to determine if seroconversion is sustained.
  • It remains unclear whether PEG-IFN is needed. TDF/NAP therapy without PEG-IFN was not studied.
  • They state that more information about flares during treatment are needed.  In this study, flares were safe and associated with beneficial outcomes.  It is not clear if therapy flares would be detrimental in those with advanced fibrosis.
  • Optimistically, they state that there are multiple competing therapies being studied (eg. small interfering RNA, and small molecule HBs-RNA destabilizer) which could be more easily administered.

My take (borrowed from authors): In a phase 2 randomized trial, “we found that addition of NAPs to TDF + pegIFN did not alter tolerability and significantly increased rates of HBsAg loss and HBsAg seroconversion during therapy and functional cure after therapy.”

A related commentary (Gastroenterol 2020; 158: 2028-32) calls for investment/study of treatment for immune-tolerant patients along with curative therapy when it becomes available.  The authors also argue for a study of long-term viral suppression with either entecavir or tenofovir alafenamide.

Plus one: N Rodriguez-Baez et al. JPGN 2020; 71: 99-105.  This study examined liver histology from 134 liver biopsies from treatment-naive children with chronic hepatitis B infection. 60% acquired infection vertically, 69% were HBeAg-positive.   Interface hepatitis was mild in 31%, moderate in 61% and severe in 6%; lobular inflammation was mild in 54%, moderate in 29% and severe in 7%. Fibrosis: 18% had no fibrosis, 59% had portal fibrosis without bridging, 19% had bridging fibrosis and 4% had cirrhosis. Alanine amnotransferase was a fairly good indicator of the severity of hepatic inflammation and extent of fibrosis.

Related blog posts:

Liver Shorts -June 2020

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SH Ibrahim et al. Hepatology 2020; 71: 1474-85.  Thorough review of liver diseases in the perinatal period and relationship of the maternal-infant interactions.  Liver diseases discussed include GALD which has “strikingly normal or near normal transaminases” despite liver failure (most common etiology).  Treatment for GALD includes IVIG (1 g/kg) along with subsequent double-volume exchange transfusion.  The review covers maternally-transmitted viral infections, fatty liver disease, and acute fatty liver disease of pregnancy (AFLP); AFLP is most commonly caused by LCHAD but can be caused by other defects in fatty acid oxidation.

RT Khalaf, RJ Sokol. Hepatology 2020; 71: 1486-98. This review focuses on intestinal failure-associated liver disease (IFALD).  The review provides an in-depth discussion of intravenous lipid emulsions and other factors implicated in the pathogenesis.

  • Risk factors: bacterial overgrowth, central line infections, recurrent sepsis, prematurity, parenteral nutrition composition, and micronutrient imbalances
  • Protective factors: early enteral nutrition, cycled parenteral nutrition, glucagon-like peptide 2, preservation of ileocecal valve, small bowel lengthening when appropriate
  • While the authors acknowledge that lipid minimization often improves cholestasis, they advise caution due to concern for both essential fatty acid deficiency and detrimental effects on brain growth.
  • Prevention of central line infections with use of ethanol locks is important and effectively reduces the rate by more than 80% (though currently costs of ethanol locks have skyrocketed: FDA Safety Initiative Complicit in Ethanol Costing $30,000 for 1 oz)
  • The authors note that long-term survival from intestinal transplantation is only 40% at 10 years indicating benefit of ongoing parenteral nutrition management if feasible.

Related blog posts:

PL Valentino et al. JPGN 2020; 70: 547-54. This article discusses potential management of Wilson disease diagnosed in infancy based on ATP7B genetic testing. Very little evidence presented.  Suggests starting Zinc therapy at an early age and monitoring for copper deficiency along with efficacy.  More precise recommendations regarding urine copper goals for children would be helpful as well.

Large (n=112, median age 38 years) prospective observational study of Acute Hepatic Porphyria. L Gouya et al. Hepatology 2020; 71: 1546-58. Key findings from EXPLORE group:

  • Chronic symptoms were noted in 65%; 46% had daily symptoms. Symptoms including body pains, trouble sleeping/tiredness, anxiety, GI symptoms (eg. nausea) and weakness.
  • During the 2-year study period, 88% experienced a total of 483 attacks; 77% of these attacks required treatment at a health care facility or hemin administration
  • Median annualized attack rate was 2.0
  • UrineDelta-aminolevulinic acid (ALA) and porphobilinogen (PBG) compared with upper limit of normal at baseline and increased further during attacks.
  • At baseline, 16% had elevations of liver aminotransferases
  • Related reference: M Balwani et al. Hepatology 2017; 66: 1314-22. Acute Hepatic Porphyrias -Review. Current recommendations include gene sequencing to confirm all biochemical cases. Biochemical tests are spot urine testing of porphobilinogen (PBG), 5-aminolevulinic acid (ALA), and porphyrins. A normal urine PBG in symptomatic patients “excludes the three most common acute hepatic porphyrias.”  For those with abnormal studies, this reference is a handy.

Automated ascites pump. F Wong et al. Liver Transplantation 2020; 26: 651-61. In this study with 30 patients, interventional radiology placement of an “alfapump” helped manage refractory ascites in cirrhosis.

Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  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

Weekend News: Elevators, Maskne, Fraudulent Mask Exemptions, Vaccine Optimism, and Taking Healthcare from Millions

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Weekend News:

:NY Times: Maskne Is the New Acne, and Here’s What Is Causing It

Maskne — the most common kind of which is acne mechanica, a.k.a. the type of acne a football player may get where the helmet rubs — is also enough of a thing that the Covid-19 task force of the American Academy of Dermatology (A.A.D.) felt compelled to release advice on the subject.

The article describes how mask can trigger acne and ways to prevent/treat this.

Related: American Academy of Dermatology: 9 WAYS TO PREVENT FACE-MASK SKIN PROBLEMS

NY Times: Don’t Whistle on the Elevator. Don’t Even Talk. (print version article title)

“The good news is: If you don’t like small talk in the elevator, those days are over,”…“Imagine if you have a 30-story office building in New York City and you’re trying to get 5,000 people in between 7 and 9 in the morning,”

From NPR:

This administration should present its ‘plan’ and pass it before taking healthcare insurance from millions.

 

How Very Early Onset-Inflammatory Bowel Disease is Different, Plus One

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A recent retrospective study (JR Kelsen et al. Inflamm Bowel Dis 2020; 26: 909-18) compares children diagnosed with inflammatory bowel disease at different age points and their outcomes.  During a 9 year study span (2008-16), there were 229 subjects diagnosed as very-early onset (<6 years, VEO), 221 diagnosed as intermediate onset (6-10 years), and 521 diagnosed as older onset (> 10 years)

Key findings:

  • VEO-IBD patients were significantly more likely to have had a diverting ileostomy and colectomy than the older patients.  Diverting ileostomy rates: 12.2%, 4.1%, and 1.2% respectively.  Colectomy rates: 7.4%, 4.1%, and 1.7% respectively.
  • Ileocecal resections were significantly higher in the older-onset IBD population. In the older group, these resections were noted in 64/521 (12.2%) compared to 1/229 (0.4%) in the VEO group and 10/221 (4.5%) in the intermediate group.
  • VEO-IBD patients had higher medication failure rates at 1 year into treatment and were more frequently readmitted to the hospital. For infliximab (IFX), failure rates were 62.4% for VEO subjects compared to 14.6% for older-onset subjects.  For adalimumab, the respective rates were 53.2% vs. 7.2%.
  • Targeted therapy was successfully used almost exclusively in the VEO-IBD population

My take: Children with VEO-IBD have a more severe disease course than older children.  Since monogenetic disorders occur in ~8% of the VEO population, targeted therapies are more likely; however; ~2% of older children also have a monogenetic disorder and as such, targeted therapy could be important in this group as well.

Related review article: J Ouahed et al. Very Early Onset Inflammatory Bowel Disease: A Clinical Approach With a Focus on the Role of Genetics and Underlying Immune Deficiencies. Inflamm Bowel Dis 2020; 26: 820-842.  This is a useful review.  A couple of key points:

  • “There are no quality studies assessing the use of nutritional approaches in VEO-IBD”
  • Stem Cell Transplantation NOT efficacious in these disorders (per Table 3): TTC7A, STXBP2, IKBKG (NEMO)

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ACG Review (Zobair Younassi, MD): NAFLD and NASH

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For PDF copy of slides: NAFLD and NASH

Dr. Zobair Younassi gave a recent virtual grand rounds –here are some of the slides:

Epidemiology:

Natural History:

  • Progression of disease is not linear
  • Fatty liver disease is a multisystem disorder.  Cardiovascular disease is leading cause of death in patients with fatty liver disease
  • Fatigue (~50%) is common with fatty liver disease

Main treatment:

  • Weight loss -Mediterranean diet may be helpful
  • Exercise
  • No FDA-approved treatments, though pioglitizone supported by AASLD for biopsy-proven NASH
  • Public health interventions are needed

Iodine Deficiency in Extremely Low Gestational Age Newborns Receiving Parenteral Nutrition

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Briefly noted: N Kanike et al. Nutrients 2020, 12(6), 1636; https://doi.org/10.3390/nu12061636 (from Kipp Ellsworth Twitter feed)

Full text: Risk of Iodine Deficiency in Extremely Low Gestational Age Newborns on Parenteral Nutrition

Background/Methods: Extremely Low Gestational Age Newborns (ELGAN) do not receive Iodine supplementation while on parenteral nutrition (PN)….We measured urine iodine levels and thyroid function tests in 50 mother–infant dyads at birth, at 1 week, 1, 2, 3 months and near discharge. In our study, 64% of mothers were iodine deficient at the time of delivery.

Key findings:

  • At 1 month of age, ELGAN on PN developed iodine deficiency (p = 0.017) and had high thyroglobulin levels of 187 (156–271) ng/mL
  • Iodine levels improved with enteral feeds by 2 months of age (p = 0.01).

My take: The authors note that “Iodine supplementation during pregnancy and postnatally should be considered to avoid iodine deficiency.”  In addition, in those at risk, there needs to be monitoring and treatment of hypothyroidism.

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Blog Case Report: Colonic Polyp & Elevated Calprotectin

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Last week, a 7 year old with a 6 month history of loose stools and rectal bleeding underwent a panendoscopy.  Prior to endoscopy, she had a calprotectin level of 1000 mcg/gram.

  • Findings: Huge (>5 cm) multilobulated polyp which was removed at stalk.  A second pass to revise stalk was completed subsequently. The histology report noted that the polyp was a benign juvenile polyp.

This case was interesting to me due to the unusual size/configuration of the polyp and the very elevated calprotectin.  I was aware of elevated calprotectin levels with polyposis (in part from a recent review of our experience with ~400 colonoscopies in our center: Full Text Link: Diagnostic Yield Variation with Colonoscopy among Pediatric Endoscopists)

Two views of large polyp from scope in descending colon

Related blog posts:

 

Data on Mask Efficacy and COVID-19 Safety –How U.S. Compares

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According to this ranking, U.S. is 58th in the world:

From Health Affairs, Full Text: Community Use Of Face Masks And COVID-19: Evidence From A Natural Experiment Of State Mandates In The US

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Healthy Microbiome: A Work in Progress, Plus Microbiome-Drug Metabolism

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A recent study (G Galazzo, N Van Best, et al. Gastroenterol 2020; 158: 1584-96) highlights the changes in microbiota diversity from birth until 11 years of age.

Full text: Development of the Microbiota and Associations With Birth Mode, Diet, and Atopic Disorders in a Longitudinal Analysis of Stool Samples, Collected From Infancy Through Early Childhood

Methods: We collected 1453 stool samples, at 5, 13, 21, and 31 weeks postpartum (infants), and once at school age (6–11 years), from 440 children (49.3% girls, 24.8% born by cesarean delivery; all children except for 6 were breastfed for varying durations; median 40 weeks; interquartile range, 30–53 weeks).

Key findings:

  • Most bacteria within the Bacteroidetes and Proteobacteria phyla were already present at 5 weeks after birth, whereas many bacteria of the Firmicutes phylum were acquired at later times in infancy.
  • At school age, many new Actinobacteria, Firmicutes, and Bacteroidetes bacterial taxa emerged.
  • The largest increase in microbial diversity occurred after 31 weeks of life.
  • Vaginal, compared with cesarean delivery, was most strongly associated with an enrichment of Bacteroides species at 5 weeks through 31 weeks.
  • From 13 weeks onward, diet became the most important determinant of microbiota composition; cessation of breastfeeding, rather than solid food introduction, was associated with changes.
  • When we adjusted for confounding factors, we found fecal microbiota composition to be associated with development of atopic dermatitis, allergic sensitization, and asthma. Members of the Lachnospiraceae family, as well as the genera Faecalibacterium and Dialister, were associated with a reduced risk of atopy.

My take: We are still learning a lot about the microbiome.  Though a ‘healthy’ microbiome is still not straight-forward determination, a good diet with plenty of fruits and vegetables has been associated with more favorable attributes.

Plus One: Bahar Javdan, et al. Personalized Mapping of Drug Metabolism by the Human Gut Microbiome. Cell, 2020; DOI: 10.1016/j.cell.2020.05.001

In this study, the authors found how variations in the microbiome had unique effects on drug metabolism.  From ScienceDaily, Can gut microbiome alter drug safety and efficacy?  The authors tested 575 FDA-approved drugs to see if they are chemically modified by one of the 21 cultured microbiomes, and then tested a subset of the drugs with all the cultured microbiomes. Here, they found microbiome-derived metabolites that had never been previously reported

Related blog posts:

 

Reducing Gastrostomy Tube Placement in Children with Aspiration & COVID-19 Tracking

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From The COVID Tracking Project: Effective Reproduction Number

These are up-to-date values for Rt, a key measure of how fast the virus is growing. It’s the average number of people who become infected by an infectious person. If Rt is above 1.0, the virus will spread quickly. When Rt is below 1.0, the virus will stop spreading.  All 50 states listed below (but hard to see) -these numbers adjust for testing frequency:

The site has each state -here are Georgia and Florida:

A recent study (McSweeney M, Meleedy-Rey P, Kerr J, Yuen JC, Fourneir G, Norris K, Larson K, Rosen R. A quality improvement initiative to reduce gastrostomy tube placement in aspirating patients. Pediatrics. 2020, 145: e20190325; DOI: https://doi.org/10.1542/peds.2019-0325) was highlighted by John Pohl in Practical Gastroenterology:

Full text summary: Reducing Gastrostomy Placement in Children with Aspiration

An excerpt:

Children equal to or less than 2 years of age with aspiration demonstrated on VFSS were included in the study…If a VFSS was abnormal and the child was less than 52 weeks gestational age, then the child either was admitted to the hospital for a trial of nasogastric (NG) breastmilk or oral thickened formula with NG breast milk. The patient then continued to work with SLP… If a repeat VFSS showed improvement in the swallowing mechanism, then work with SLP and trialing with thickened feeds continued until the aspiration had resolved as demonstrated by VFSS. However, if a repeat VFSS still showed aspiration, a child was considered a candidate for gastrostomy placement…

In total, 6125 patients at 2 years of age or less underwent a VFSS during the 4-year study period, and 1668 of these patients had aspiration or penetration… 94 of the patients with aspiration or aspiration and penetration on their first VFSS (12.2%) and 31 of the patients with penetration only on their first VFSS (3.4%) eventually required gastrostomy placement…

Gastrostomy placement in this patient population fell from 10.9% at the beginning of the study to 5.2% at the end…

The number of emergency room visits and hospitalizations in the patient group without gastrostomies did not increase during the study with this same patient group having significantly less emergency room visits and hospitalizations compared to those children who had undergone gastrostomy placement

My take: This study shows that conservative therapy allows most children (<2 yrs) to avoid gastrostomy tube placement

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