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. I have authored numerous publications/presentations including original research, case reports, review articles, and textbook chapters on various pediatric gastrointestinal problems. 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 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, 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 15 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. For many families, more practical matters 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 – 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. I like to read, walk/hike, exercise, swim, and play tennis with my free time as well as go to baseball games. I do not have any financial relationships with pharmaceutical companies or other financial relationships to disclose. I have participated in industry-sponsored research studies.

How Likely/Persistent is Eosinophilic Esophagitis with Peanut Oral Immunotherapy

BL Wright et al. Clin Gastroenterol Hepatol 2021; 19: 1151-1159. Gastrointestinal Eosinophil Responses in a Longitudinal, Randomized Trial of Peanut Oral Immunotherapy

Background: “The incidence of EoE during OIT has been estimated at 2.7%.” (AJ Lucendo et al. Ann Allergy Asthma Immunol 2014; 113: 624-629)

Methods: Twenty adults with IgE-mediated peanut allergy were randomly assigned to groups given peanut OIT (n = 15) or placebo (n = 5) in this prospective study. Serial gastrointestinal biopsies were collected at baseline (n = 21, 0 weeks), following dose escalation (n = 10, 52 weeks), and during the maintenance phase (n = 11, 104 weeks)

Key findings:

  • At baseline: 3 of the 21 subjects (14%) had esophageal peak eosinophil counts ≥15 eos/hpf and all subjects had dilated intercellular spaces (DIS)
  • At 52 weeks: OIT induced or exacerbated esophageal eosinophilia (EoE) at 52 weeks with peak eosinophil counts ≥15 eos/hpf in 4 of 7 patients [57%] who did not have EoE at baseline. EoE did not develop in patients receiving placebo
  • At 104 weeks: In 4 of 6 participants (67%), OIT-induced EoE and gastrointestinal eosinophilia resolved by the end of the maintenance phase
  • One patient developed a clinical diagnosis of EoE.

The discussion notes overlap between EoE and IgE-mediated food allergy. The risk of EoE in patients with IgE-mediated food allergy is 118 times that of the general population (4.7% vs 0.04%) (J Allergy Clin Immunol Pract 2017; 5: 369-375). Also, the authors note that in this study all of the peanut allergic subjects had evidence of epithelial barrier dsyfunction.

My take: This small study shows, that for most adult patients, the development of EoE during OIT is often transitory.

Related blog posts:

2021 AGA Guidelines For Crohn’s Disease

A series of articles details the 2021 AGA Guidelines for Crohn’s disease (CD) including a clinical practice guideline (pg 2496-2508), a clinical decision support tool (2509-2510), a spotlight summary (pg 2511), a technical review (2512-2557), and a review of the recommendations (pg 2557-2262). I will highlight the first article.

JD Feuerstein et al. Gastroenterol 2021; 160: 2496-2508. Full text: AGA Clinical Practice Guidelines on the Medical Management of Moderate to Severe Luminal and Perianal Fistulizing Crohn’s Disease

Full text: Spotlight

For me the most important of their recommendations was #7:

  • In adult outpatients with moderate to severe CD, the AGA suggests early introduction with a biologic with or without an immunomodulator rather than delaying their use until after failure of 5-aminosalicylates and/or corticosteroids.

Other points:

From Spotlight:

Radiomic Imaging in Crohn’s Disease

X Li et al. Gastroenterol 2021; 160: 2303-2316. Development and Validation of a Novel Computed-Tomography Enterography Radiomic Approach for Characterization of Intestinal Fibrosis in Crohn’s Disease

Methods: This article describes the development a computed-tomography enterography (CTE)–based radiomic model (RM). This retrospective multicenter study included 167 CD patients who underwent preoperative CTE and bowel resection. 1454 radiomic features were extracted from venous-phase CTE and a machine learning–based RM was developed based on the reproducible features using logistic regression. The RM was validated in an independent external test cohort recruited from 3 centers.

Key findings:

  • In the training cohort, the area under the ROC curve (AUC) of RM for distinguishing moderate–severe from none–mild intestinal fibrosis was 0.888.
  • In the test cohort, the RM had an AUC of 0.816.
  • RM was more accurate than visual interpretations by either radiologist (radiologist 1, AUC = 0.554; radiologist 2, AUC = 0.598; both, P < .001) in the test cohort

My take: This CT approach with RM allowed for accurate characterization of intestinal fibrosis in CD. The images look pretty cool too.

SC Option for Infliximab

S Schreiber, S Ben-Horin et al. Gastroenterol 2021; 160 2340-2353. Full text: Randomized Controlled Trial: Subcutaneous vs Intravenous Infliximab CT-P13 Maintenance in Inflammatory Bowel Disease

Methods: Overall in this phase 1 randomized, open-label study in patients with either ulcerative colitis or Crohn’s disease, 66 and 65 patients were randomized to CT-P13 SC (every 2 weeks) and CT-P13 IV, respectively

Key findings: The pharmacokinetic noninferiority of CT-P13 SC to CT-P13 IV, and the comparable efficacy, safety, and immunogenicity profiles

These findings are in agreement with similar studies performed in patients with Rheumatoid Arthritis.

My take: If confirmed with additional studies, it is likely that SC infliximab treatment will be a useful alternative to intravenous infliximab. This is similar to data presented with vedolizumab which is currently administered intravenously.

Graphical Abstract

Looking at the Mycobiome to Distinguish Clostridium difficile Infection vs. Carriage

Y Cao et al. Gastroenterol 2021; 160: 2328-2339. Fecal Mycobiota Combined With Host Immune Factors Distinguish Clostridioides difficile Infection From Asymptomatic Carriage

Key findings:

  • The ratio of Ascomycota to Basidiomycota was dramatically higher in patients with CDI than in Carrier and Control (P < .05).
  • Using 4 fungal operational taxonomic units combined with 6 host immune markers in the random forest classifier can achieve very high performance (area under the curve ∼92.38%) in distinguishing patients with CDI from Carrier.

My take: It is interesting that fecal fungal diversity (mycobiome), in addition to bacterial diversity, is reduced in those with Clostridium difficile infection (CDI) compared to both control groups and those with Clostridium difficile asymptomatic carriage.

Related blog posts:

Another reason to get vaccinated

Is Non-Celiac Wheat Sensitivity an Autoimmune Disorder?

A recent study (P Mansueto et al. Am J Gastroenterol 2021; 116: 1015-1023. Autoimmunity Features in Patients With Non-Celiac Wheat Sensitivity). Thanks to Ben Gold for this reference.

The authors prospectively and consecutively studied 91 patients with Non-Celiac Wheat Sensitivity (NCWS) (F?M ratio 7:1); 76 healthy blood donors (HBD) and 55 patients with a diagnosis of irritable bowel syndrome (IBS) unrelated to NCWS served as controls.

NCWS was diagnosed based on absence of celiac serology, absence of villous atrophy (while receiving a gluten-containing diet), negative IgE-testing for wheat allergy (either serum or skin prick tests) along with resolution of symptoms off wheat and symptom reappearance wiht a DBPC wheat challenge.

Key findings:

  • Twenty-three patients with NCWS (25.3%) presented with autoimmune diseases (ADs); autoimmune thyroiditis (16 patients, 17.6%) was the most frequent. The frequency of ADs was higher in patients with NCWS than in HBD (P = 0.002) and in patients with IBS (P = 0.05).
  • In the NCWS group, antinuclear antibodies tested positive in 71.4% vs HBD 19.7%, and vs patients with IBS 21.8% (P < 0.0001 for both).
  • The frequency of extractable nuclear antigen antibody (ENA) positivity was significantly higher in patients with NCWS (21.9%) than in HBD (0%) and patients with IBS (3.6%) (P = 0.0001 and P = 0.004, respectively).
  • Among NCWS with comorbid autoimmunity, duodenal lymphocytosis was present in ~80% and others had eosinophilic infiltration (~90%), both suggestive of ongoing immune activation. (Duodenal eosinophilic infiltration was also noted in ~60% of those who had absence of autoimmune disease too)

The associated editorial by Galipeau et al notes that only 16% of those who self-report as “gluten-sensitive” will actually fulfill the current consensus criteria for a diagnosis of NCWS. The diagnosis is problematic because of the absence of a validated biomarker. While the current study shows association with autoimmune markers, other studies have shown some have markers of immune activation and others with non-IgE-mediated food sensitivities.

My take: These type of studies help us understand NCWS. Yet, without a more definitive biomarker, many people will be on a gluten-free diet needlessly.

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Dry Tortugas National Park (FL)

New Way to Diagnosis of Wilson’s Disease: ATP7B Peptides

CJ Collins, F Yi et al. Gastroenterol 2021; 160: 2367-2382. Full text: Direct Measurement of ATP7B Peptides Is Highly Effective in the Diagnosis of Wilson Disease

There continues to be challenges in the diagnosis of Wilson’s disease (WD). Genetic testing, per the authors and Vasrome (varsome.com), have found more than 649 pathogenic mutations and another 692 mutations that are VUS. Definitive diagnosis with genetic testing requires 2 known pathogenic variants. Other features, including Kayser-Fleischer rings and ceruloplasmin, have limited sensitivity and/or specificity.

Methods: Two hundred and sixty-four samples from biorepositories at 3 international and 2 domestic academic centers and 150 normal controls were used.

Key findings:

  • Two ATP7B peptides were found to have a sensitivity of 91.2%, specificity of 98.1%, positive predictive value of 98.0%, and a negative predictive value of 91.5%.
  • In patients with normal ceruloplasmin concentrations (>20 mg/dL), 14 of 16 (87.5%) were ATP7B-deficient. In patients without clear genetic results, 94% were ATP7B-deficient.

Discussion: As with other tests, ATPB7 peptide testing has limitations. Most patients with WD have pathogenic mutations that often result in protein misfolding, absence of decay of messenger RNA and enhanced degradation; hence, low ATPB7 levels; however, disease-causing mutations that affect protein activity but not protein concentration will generate false-negative results.

My take: “ATP7B peptide analysis identified WD patients in a large majority of cases and reduced ambiguities resulting from genetic analysis and Cp (ceruloplasmin) levels. This noninvasive assay can serve as an adjunctive test for the diagnosis of WD and is expected to fundamentally advance the use of proteomic technology for a rapid screening tool.

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Risks of Vaccines Compared to COVID-19 Infection in 12-17 Year Olds

NY Times: Covid Is a Greater Risk to Young People Than the Vaccines (July 4, 2021)

This article elaborates on the risks of vaccination, especially due to myocarditis, compared to the risks posed by COVID-19 infection. Even using very cautious estimates, the authors find that the risks of hospitalizations, cardiac morbidity, and deaths are likely to be much lower in those who receive the vaccine.

Key points:

  • “Among the 6.14 million Americans 17 and under who have been fully vaccinated, there have been 653 possibly related hospitalizations lasting a day or longer…. If that rate holds, it means that if all 73 million Americans ages 17 and under are eventually vaccinated, there will be around 7,700 hospitalizations.”
  • “So far, 326 Americans age 17 and younger have died of Covid-19.”
  • “If the coronavirus were eventually to infect all 73 million children in the United States, we would conservatively expect Covid-19 to be responsible for around 14,600 hospitalizations….[and] lead to over 27,000 additional hospitalizations from the [MIS-C] syndrome.”
  • Unlike hospitalizations related to vaccines which have typically been brief and uneventful, “Covid-related hospitalizations in adolescents can be long and complicated, with nearly one-third requiring patients to enter the intensive care unit.”
  • “Bad things inevitably happen to a small number of people after any vaccination, a few caused by the vaccines, but most not…The virus is more dangerous.”

My take: 12-17 year olds are at less risk from COVID-19 infection than other age groups, however, this risk is still greater risk than the risk of vaccination. Protecting them with immunizations also protects other vulnerable populations and may decrease the risk of vaccine-resistant variants.

Related article: Eric Topol NY Times: It’s Time for the F.D.A. to Fully Approve the mRNA Vaccines An excerpt: “Now more than 180 million doses of the Pfizer vaccine and 133 million of Moderna’s have been administered in the United States, with millions more doses distributed worldwide. In the history of medicine, few if any biologics (vaccines, antibodies, molecules) have had their safety and efficacy scrutinized to this degree…it’s frankly unfathomable that mRNA vaccines have been proved safe and effective in hundreds of millions of people and yet still have a scarlet “E”.”

Persistent Villous Atrophy in Celiac Disease Despite a Gluten-Free Diet

A recent study (F Fernandez-Banares et al. Am J Gastroenterol 2021; 116: 1036-1043. Persistent Villous Atrophy in De Novo Adult Patients With Celiac Disease and Strict Control of Gluten-Free Diet Adherence: A Multicenter Prospective Study (CADER Study) shows that there is a high likelihood of persistent villous atrophy among adults with celiac disease (CD) despite adherence with a gluten-free diet (GFD). Thanks to Ben Gold for showing me this paper.

Key findings:

  • Among 76 patients (median age 36.5 years) who were prospectively followed for 2 years, persistent villous atrophy was observed in 40 (53%). In this group, 72.5% were asymptomatic (based on Likert scales) and 75% had negative serology
  • Detectable fecal gluten immunogenic peptides (f-GIPs) were present in at least one sample in 69% of patients. (Two samples obtained at f/u visits which were ~every 6 months during study)
  • Excellent or good adherence to GFD was demonstrated in 68.4% of patients based on dietetic evaluations. Only 6 (8%) were clearly nonadherent
  • “There were no significant differences in the rate of clinical and serological remission between patients with villous atrophy and those with mucosal recovery”
  • The authors did not find potentially modifiable predictive factors

Discussion:

  • The authors note that serology is “not useful for monitoring patients on a GFD.” Anti-TTG2 and EMA, in a recent meta-analysis, had a pooled sensitivity of around 50%.
  • “Adults are significantly less likely than children to normalize their duodenal histology.”

Editorial:

  • The associated editorial by Rej et al (pg 946-948) outline a personalized approach for dealing with persistent villous atrophy:
    • In those with persistent symptoms/positive GIPs/elevated serology/micronutrient deficiency, the first step is careful dietetic assessment. After this, endoscopy could be considered to confirm presence or absence of mucosal healing.
    • In those with no symptoms and no abnormalities, use of monitoring endoscopy needs to be weighed against the costs as well as potential complications.
    • Other points in the editorial: 1. GIPs have poor concordance with mucosal healing and 2. causes of poor mucosal healing include the following: natural slow healing process, super sensitive to gluten, ongoing gluten exposure, and refractory celiac disease.

My take: This study shows that there is ongoing gluten exposure in the majority of patients even in those with excellent or good adherence to a GFD; in addition, it shows that clinical/serological markers are NOT effective in predicting mucosal healing in adults. Nevertheless, it is not clear that followup endoscopy is beneficial.

Related blog posts:

Forbes (7/1/21): 99.5% Of People Killed By Covid In Last 6 Months Were Unvaccinated, Data Suggests

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