Category Archives: Uncategorized

BRUEs in Boston –Two Punch Study

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DR Duncan et al. J Pediatr 2024; 272: 114128. Brief Resolved Unexplained Events Symptoms Frequently Result in Inappropriate Gastrointestinal Diagnoses and Treatment

In this prospective cohort study from Boston Children’s (2017-2022, n=157), the authors examined diagnostic evaluations in children presenting with Brief Resolved Unexplained Events (BRUEs).

Key findings:

  • Only 28% (20% during the hospitalization, 8% afterwards) underwent VFSS with 71% abnormal.
  • 42% of infants had their BRUE attributed to GERD, and 33% were treated with acid suppression during follow-up
  • Provision of GERD diagnosis was associated with a delay in making an aspiration diagnosis. 10% (6/66) of patients with “GERD” diagnosis subsequently had swallow studies –all were abnormal. Mean diagnostic delay was 56 days.

Discussion points:

  • The approach of using symptoms to determine evaluation of BRUEs has been advised by AAP clinical practice guidelines (2016 & 2019); “however, our results suggest that reliance on these clinical characteristics may result in negative outcomes.”
  • Most aspiration in infants is silent aspiration and not detected by clinical feeding evaluation (CFE) in the absence of a VFSS. “It is concerning that 63% of patients had CFE alone without confirmatory VFSS in the present cohort, and it may be that this practice is even more common in other centers.” Silent aspiration can lead to repeat hospital visits and even long-lasting pulmonary damage including bronchiectasis.
  • Establishing a GERD diagnosis likely increases unnecessary (& potentially harmful) acid suppression

My take: The two punches in this study:

  1. Clinicians cannot diagnose aspiration based on history or bedside feeding evaluations. Objective testing (e.g. VFSS) is needed if there are concerns for dysphagia
  2. Inappropriate diagnosis of GERD may cause harm. GERD medications have been associated with increased infections and may increase risk for allergies.

The role of aspiration in causing BRUEs has been well-recognized since 2017 (see below) by the same group in Boston. It is likely that evaluation of dysphagia is even less frequent in other medical centers.

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Double Arch at Arches National Park

ChatGPT4 Outperforms GI Docs for Postcolonoscopy Surveillance Advice

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PW Chang et al. Clin Gastroenterol Hepatol 2024; 22: 1917-1925. ChatGPT4 Outperforms Endoscopists for Determination of Postcolonoscopy Rescreening and Surveillance Recommendations

Text input of de-identified data into ChatGPT4 from 505 consecutive patients undergoing colonoscopy between January 1 and April 30, 2023. Key findings:

  • ChatGPT4 recommendations were in closer agreement with the USMSTF Panel (85.7%) than gastroenterology practice recommendations with the USMSTF Panel (75.4%) (P < .001).
  • Of the 14.3% discordant recommendations between ChatGPT4 and the USMSTF Panel, recommendations were for later screening in 26 (5.1%) and for earlier screening in 44 (8.7%) cases. 

My take: Incorporating AI in deciding follow-up surveillance is likely to be a helpful tool.

Related article: K-H Yu et al. NEJM 2024; 390: 1895-1904. Medical Artificial Intelligence and Human Values. This article discusses how human values affect the results of AI advice.

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Mesa Arch at Canyonland National Park

Mom, Can We Get a Dog (& a Sibling)? I Don’t Want to Get Crohn’s Disease

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M Xue et al. Clinical Gastroenterology and Hepatology, Volume 22, Issue 9, 1889 – 1897.e12. Open Access! Environmental Factors Associated With Risk of Crohn’s Disease Development in the Crohn’s and Colitis Canada – Genetic, Environmental, Microbial Project

Methods: The authors prospectively followed 4289 healthy first-degree relatives (FDRs) of patients with CD from the Crohn’s and Colitis Canada – Genetic, Environmental, Microbial (CCC-GEM) project. Regression models identified environmental factors associated with future CD onset and their association with pre-disease biological factors, including altered intestinal permeability measured by urinary fractional excretion of lactulose to mannitol ratio (LMR); gut inflammation via fecal calprotectin (FCP) levels; and fecal microbiome composition through 16S rRNA sequencing.

Key findings:

  • Over a 5.62-year median follow-up, 86 FDRs developed CD
  • Living with a dog between ages 5 and 15 (hazard ratio [HR], 0.62; P = .034) was associated with decreased CD risk
  • Living with a dog was associated with reduced LMR, altered relative abundance of multiple bacterial genera, and increased Chao1 diversity.
  • Living with a large family size in the first year of life (HR, 0.43; P = .016) was associated with decreased CD risk
  • Having a bird at the time of recruitment (HR, 2.78; P = .005) was associated with an increased CD risk (though there were relatively few FDRs with birds at baseline, n=136)
  • Limitations: questionnaire-based assessments of environmental exposure can be subject to recall bias

My take (borrowed from authors): “Our findings contribute to the growing evidence supporting the potential health benefits of exposure to pets, particularly dogs, as a potential preventive strategy for individuals at risk of developing CD.” Having a dog during childhood may reduce the later risk of CD by ~40%.

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Dr. Praveen Goday: Tips on Managing Feeding Problems (Part 1)

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Dr. Goday gave our group a great lecture on pediatric feeding disorders. I’ve included many of his slides along with some of my notes. There may be errors in omission and transcription on my part.

Differences between picky eating, pediatric feeding disorder, and ARFID

  • 70% of picky eating is inherited.
  • If there are sequelae from picky eating, this indicates that the child has a pediatric feeding disorder.  There are 4 potential domains to pediatric feeding disorders: medical dysfunction, feeding skills dysfunction, nutritional dysfunction and psychosocial dysfunction (this is more subjective than other domains)
  • Pediatric feeding disorder (PFD) is a better term than “behavior” feeding disorder because many children have underlying contributing disorders like eosinophilic esophagitis (EoE) or aspiration/swallow dysfunction
  • ARFID is a diagnosis used by psychologists. It is when purely psychosocial concerns leads to nutrition dysfunction. The diagnosis is likely best used in older children who are mostly neurotypical and have normal development.  In younger children, it is important to assess for underlying disorders like oromotor discoordination and EoE

Strategies to prevent picky eating:

  • Breastfeeding (varied tastes in breastmilk)
  • Responsive feeding (feeding when hungry)
  • Solids [lumpy] (especially 6-9 months)
  • Multiple-varied exposures
  • Prevention/treatment: Praise at meal times, non-food rewards, Ellyn Satter’s advice (parents decide when, where, and what is offered & child decides how much

Increased risk of developing picky eating: FPIES, multiple allergies

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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.

Where Will We Be Without Formulas for Premature Babies?

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S.A Abrams, R.J. Shulman. The American Journal of Clinical Nutrition, https://doi.org/10.1016/j.ajcnut.2024.08.028. Open Access! What would happen in the United States if there were no cow milk-based preterm infant nutritional products: Historical perspective and evaluation of nutrient-related challenges

Background: “Recent legal action (1) has raised the possibility that preterm cow milk-based infant nutritional products (PCMBPs) may either not be produced and available in the United States or may require parental consent and warnings making them extremely difficult for caregivers to use and families to accept (2).”

Key points:

  • “Evidence that unfortified human milk is inadequate to meet the nutrient needs of small preterm infants has been present for over 100 years (6). Until the late 1970’s and early 1980’s, there were limited widely available solutions to either fortify or replace human milk for preterm infants and these were often based on providing feedings of concentrated evaporated cow milk; now recognized as woefully inadequate and unsafe (7 ). At that time, specialized formulas that were high in energy, protein, and micronutrients were widely introduced into the market. Early studies confirmed faster growth of infants fed such products compared to unfortified human milk or full-term formula (8) and their use became widespread by by the mid-1980s.”
  • “The availability of PCMBPs as well as a human milk-based human milk fortifier has led to relatively less frequent and severe nutritional failure in very low birth weight, less than 1500 g (VLBW) infants than in earlier eras. Nonetheless growth failure remains a current problem, especially in the smallest of infants, that is, those less than 1000 g birth weight and less than 25 weeks post-menstrual age at birth (12).”
  • “Inadequate growth and mineralization can be expected to lead to long-term developmental disability, bone demineralization, and frank rickets”
  • “Even with such improvements in policy to support breastfeeding and human milk donations, it is unlikely that an all human milk-based diet could be available for many years if ever for most of the preterm infants born in the US each year, either in the NICU or after hospital discharge.”
  • “Supplements for infants who are over a year of age.. are not suitable for preterm infants, especially those in the first 6 to 9 months after birth. They have relatively high osmolality and nutrient levels, would pose substantial risks of intolerance, and would not meet the specific nutrient requirements of this population.”
  • “The process of individualizing or creating multi-component fortification strategies would be daunting and carries risks of contamination, preparation errors, and tolerance issues. Without proper fortification, preterm infants are at a high risk of growth failure and its associated negative impacts on development and even survival.”

My take: Experts in the field of neonatal nutrition are worried that recent litigation will negate decades of nutritional advances in neonatal care. This is a very real threat. In addition to more complications, the litigation will result in much greater expenses for all infants/families.

Related blog post: Proliferation of Formula Lawsuits In Necrotizing Enterocolitis

Canyonlands National Park, Utah

Vancomycin for Inflammatory Bowel Disease in Patients with Primary Sclerosing Cholantgitis

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E Ricciuto et al. Aliment pharmacol ther 2024; 59: 1236-1247. Oral vancomycin is associated with improved inflammatory bowel disease clinical outcomes in primary sclerosing cholangitis-associated inflammatory bowel disease (PSC-IBD): A matched analysis from the Paediatric PSC Consortium

This was a retrospective study from 54 centers with 113 PSC-IBD pediatric patients receiving vancomycin (median age 12.7 years, 63% male). The matched cohort included 70 vancomycin-treated and 210 untreated patients. Clinical remission was defined as physician global assessment (PGA) of zero. It is noted that the Pediatric PSC consortium included 1362 patients at the time of this study; only 11% (n=113) were treated with vancomycin for at least 3 months. The median dose of vancomycin was 17 mg/kg/day and median duration was 2.5 years.

Key findings:

  • Vancomycin was associated with greater odds of IBD clinical remission (odds ratio [OR] 3.52, 95% CI 1.97-6.31; adjusted OR [aOR] 5.24, 95% CI 2.68-10.22).
  • Vancomycin was associated with increased odds of endoscopic remission (aOR 2.76, 95% CI 1.002-7.62; N = 101 with data), and with lower CRP (p = 0.03) and higher hemoglobin and albumin (both p < 0.01).
  • At baseline, prior to vancomycin, 34% (30/88) were in clinical remission; this increased to 60% (52/86) after 6 months of treatment. After ~ 1 year, 71% (55/78) of children treated with vancomycin were in remission, compared with 35% who had not receive the antibiotics.
  • Ursodeoxycholic acid use: 53% for vancomycin-treated and 82% of control group (P<0.001). Other cotherapies were similar including infliximab (36% vs. 27%) and vedolizumab (13% vs 7%)
  • Only 28 vancomycin-treated patients had baseline and f/u colonoscopy data available. 46% of this subgroup had endoscopic remission compared to 26% of matched untreated controls.

In the discussion, the authors acknowledge the limitations of a retrospective observational study. RCTs are quite difficult with rare disorders, especially in children. In addition, the exact mechanisms for vancomycin efficacy remain unclear -possibly microbial changes or its effects on bile acids. They note that many patients treated with vancomycin had mild clinical activity at baseline. Though, even this population may benefit with resolution of clinical inflammation which could reduce the risk of colorectal cancer.

My take: In patients with PSC-IBD, the use of vancomycin for IBD should be a consideration especially in those who have not responded adequately to other treatments.

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NEJM: Pharmacologic Treatment of Reflux in Infants?

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JR Barzilay et al. N Engl J Med 2024;391:960-962. Medication for Gastroesophageal Reflux Disease in Infants.

A recent case vignette of a 3 month old with reflux symptoms without response to dietary changes and positioning offers two potential management options. “Option 1” author advocates for use of a PPI (which I do NOT agree with):

“If conservative measures have been performed appropriately and a pediatric gastroenterology referral has been made, I would consider a short trial of medication, in accordance with guidelines from the North American and European Societies for Pediatric Gastroenterology, Hepatology, and Nutrition.2… in my experience, many pediatric gastroenterologists would conclude, on the basis of clinical symptoms, that the infant may have reflux esophagitis and would prescribe a trial of medication before considering invasive diagnostic procedures…There is no convincing evidence to support a difference between PPIs and histamine2-receptor antagonists in controlling symptoms of reflux.3 I recommend a 4-week trial of omeprazole with continuation of the nonpharmacologic treatments. If the medication is not effective, I would consider increasing the dose before terminating the trial. A PPI should not be discontinued abruptly if it has been used for several weeks, since rebound gastric hyperactivity may occur.”

“Option 2” author argues against use of medications:

“Gastric-acid inhibitors such as PPIs are often used in infants such as this one, even though there are no published studies supporting treatment.2 Several studies have indicated that PPIs and histamine2-receptor antagonists are ineffective for treating symptoms associated with infant reflux in the absence of endoscopically proven esophagitis.2….PPIs have been associated with bacterial overgrowth, respiratory infections, viral gastrointestinal illness, drug interactions, and adverse long-term bone health. The current recommendation from the North American and European Societies for Pediatric Gastroenterology, Hepatology, and Nutrition is to use PPIs (or histamine2-receptor antagonists if PPIs are contraindicated or unavailable) only in infants who have endoscopy-proven esophagitis.4“

My take:

  1. It is a mistake to publish this vignette reinforcing the idea that using a PPI in this setting is a good medical decision. Though use of a PPI is common in infants, it is rarely beneficial
  2. The vignette missed an opportunity to emphasize that some infants with reflux symptoms have oropharyngeal dysfunction, especially in those with brief resolved unexplained events (BRUEs)
  3. “Option 1” lists several fallacies —a. most pediatric GIs would NOT conclude that this infant would have reflux esophagitis –most reflux is non-erosive (especially in infants), b. even if PPIs were effective, there is not a strong argument for a 4 week trial in this age group. If PPIs were effective, response to treatment should be much quicker, and c. in this age group, a slow wean off PPIs is unnecessary. There is no proof that there is rebound gastric hyperactivity in infants.

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OpenBiome Suspending FMT Shipments

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Link: OpenBiome Voluntarily Suspends FMT Shipments

An excerpt:

On September 29, 2024, OpenBiome will voluntarily suspend the distribution of investigational Fecal Microbiota Transplants (FMT) for patients with recurrent Clostridioides difficile infection (C. diff)...

Recent interaction with the FDA has informed our decision to voluntarily suspend the distribution of all investigational FMT as we continue to seek clear direction on aligning our operations with the final Enforcement Policy published in 2022. Our commitment has always been to adhere to FDA regulations and guidelines for the manufacture and distribution of investigational FMT as a therapeutic option for patients with C. diff. Thus, this is not a safety or quality matter. Investigational FMT preparations provided by OpenBiome are manufactured and distributed in compliance with current good manufacturing practices (cGMP).    

We continue to hear from clinicians, our frontline partners, that despite the availability of FDA-approved therapeutics, there remain patients who do not respond to these treatments and, according to clinical guidelines, should have access to traditional FMT. ..

  1. Contact us. If you have a patient suffering from severe or fulminant C. diff, please contact us at 617-575-2201 or info@openbiome.org to discuss options.
  2. Share your thoughts. We believe the FDA would benefit greatly from hearing directly from survivors and their advocates about the urgent need for continued access to rigorously screened and tested FMT. If you or your C. diff patients are willing, please submit comments to ocod@fda.hhs.gov with a copy to Dr. David Kaslow, director Office of Vaccines Research and Review, at david.kaslow@fda.hhs.gov, and Dr. Peter Marks, director of the Center for Biologics Research and Evaluation at peter.marks@fda.hhs.gov. Or you may share your experiences with us directly using this FORM.  

My take: As FDA-approved therapeutics have not received a pediatric indication, NASPGHAN involvement to try to keep FMT available for children would be a worthwhile endeavor. In the absence of having FMT available from OpenBiome, NASPGHAN experts could provide guidance on best practices for refractory C diff.

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Teduglutide Study on Parenteral Nutrition -It Does NOT Reduce Costs

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U Cucinotta et al J Pediatr 2024; https://doi.org/10.1016/j.jpeds.2023.113882. The Impact of Teduglutide on Real-Life Health Care Costs in Children with Short Bowel Syndrome

It is disappointing that in this study, the authors conclusions in the abstract state the following: “Treatment with teduglutide is associated with a significant reduction in the annual costs of HPN but still remains expensive because of the drug itself.”

Key findings from the study do NOT support this concclusion:

  • In the treated group, the median total costs of home parenteral nutrition (HPN) significantly decreased after 1 (P < .001) and 2 years of treatment (P < .001) from 59,454 euros/year/patient to 43 885 euros/year/patient and 34,973 euros/year/patient, respectively
  • When we compared patients treated and not treated, the total HPN costs/year/patient were similar at baseline (P = .6) but were significantly lower in the teduglutide-treated group after 1 (P = .006) and 2 years of treatment (P < .001)
  • When we added the cost of teduglutide into the analysis, the total cost increased significantly in the treated group and remained much greater even after modeling a reduction in the cost of the drug to one-third the present cost and PN weaning (P < .001).

The study’s conclusion is like someone trying to tell me they saved money at a fancy restaurant if they just took the caviar off the bill. Guess what –it wasn’t less expensive!

My take: The conclusion from this article should be straight-forward: the costs were much greater in patients receiving teduglutide. It will remain more expensive even if the drug costs improve quite a bit. In addition, there are other additional costs of teduglutide if one follows the monitoring recommendations.

Related study: PW Wales et al. J Pediatr Gastroenterol Nutr. 2024;79:290–300. Long-term teduglutide associated with improved response in pediatric short bowel syndrome-associated intestinal failure. Safety concerns in this study (n=78 treated patients): out of 12 patients with positive antidrug antibodies, neutralizing activity was detected in four patients. There were no reported incidences of colorectal polyps

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Acute Pancreatitis in Children with Inflammatory Bowel Disease

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A Anafy et al. JPGN 2024; 79:325–334. Acute pancreatitis in children with inflammatory bowel disease: Risk factors, clinical course, and prognosis

In this retrospective study with 376 children, Key Findings:

  • 4% of patients with pediatric IBD developed acute pancreatitis (AP)
  • The presumed etiology for AP in all IBD patients was IBD-related: IBD flare-up in five, side effects of medications in two, and undetermined in seven. 
  • The only risk factor for AP development among IBD patients was IBD‐associated arthritis (23% vs. 3% for IBD‐non‐AP).
  • Extracolonic Crohn’s disease emerged as a negative risk factor for AP: it was present in only 2/13 (15%) IBD‐AP patients compared to 20/39 (51%) IBD‐non‐AP patients (p = 0.05). Patients who receive induction therapy with nutrition (exclusive enteral nutrition or Crohn’s disease exclusion diet) were less likely to be present in the IBD‐AP group (1/12 [8%] vs. 17/39 [44%] IBD non-AP patients, p = 0.04.
  • This study population, at the time of AP, had a relatively high number treated with ASA agents (66%; 11/14 AP-IBD and 26/42 Non-AP-IBD)), 27% with azathioprine (6/14 with AP-IBD and 9/42 Non-AP-IBD), and low number receiving biologics (18%, 2 AP-IBD and 8/42 Non-AP-IBD

My take: This study shows that acute pancreatitis is common in children with inflammatory bowel disease.