Category Archives: Pediatric Gastroenterology Intestinal Disorder

Potential Bias with Interpreting Rumination Outcomes

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MR Jia et al. J Pediatr Gastroenterol Nutr. 2024;79:850–854. Delay in diagnosis is associated with decreased treatment effectiveness in children with rumination syndrome

In this retrospective single-center study with 247 patients, the authors evaluated whether the time from symptom onset to diagnosis over time and whether it was associated with symptom resolution.

Key findings:

  • The median age at symptom onset was 11 years and median age at diagnosis was13 years
  • Among the 164 children with outcome data, 47 (29%) met criteria for symptom resolution after treatment
  • A longer time to diagnosis was associated with a lower likelihood of symptom resolution after treatment (p = 0.01)

In the discussion, the authors note that “we suspect that one contributing factor to worse outcomes associated with diagnostic delays is the excessive testing leading to over‐medicalization of DGBIs…Our findings are the first to show that diagnostic delay contributes to poorer outcomes in children with RS, which highlights the importance of a timely diagnosis.” In fairness to the authors, other parts of the manuscript state that the delay in diagnosis is associated with worse outcomes but does not attribute causality.

Limitations:

  • The patient cohort is derived from a specialized referral center (Nationwide Children’s)
  • Recall bias

My take:

  1. While I concur that a timely diagnosis of rumination syndrome is useful, it is unproven that a delayed diagnosis contributes to a worse outcome. The outcome differences could more easily be explained by a selection bias. Patients who never recovered from rumination symptoms previously may be less likely to respond to treatment regardless of when treatment is instituted. Perhaps attributing poor outcomes to delayed diagnosis, rather than a selection bias, is due to a confirmation bias.
  2. Another important finding is that the more than 70% of patients did NOT have resolution of their symptoms. Realizing that many patients have some symptoms after treatment helps gastroenterologists set reasonable goals.

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LIBERTY Trials for Subcutaneous Infliximab

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SB Hanauer, BE Sands, et al. Gastroenterology 2024;167: 919-923. Open Access PDF! Subcutaneous Infliximab (CT-P13 SC) as Maintenance Therapy for Inflammatory Bowel Disease: Two Randomized Phase 3 Trials (LIBERTY)

Methods: Two randomized, placebo-controlled, double-blind studies were conducted in patients with moderately to severely active CD or UC and inadequate response or intolerance to corticosteroids and immunomodulators. All patients received open-label CT-P13 IV 5 mg/kg at weeks 0, 2, and 6. At week 10, clinical responders were randomized (2:1) to CT-P13 SC 120 mg or placebo every 2 weeks until week 54 (maintenance phase) using prefilled syringes. 

Key findings:

  • At week 54 in the CD study, statistically significant higher proportions of CT-P13 SC–treated patients vs placebo-treated patients achieved clinical remission (62.3% vs 32.1%; P < .0001) and endoscopic response (51.1% vs 17.9%; P < .0001)
  • In the UC study, clinical remission rates at week 54 were statistically significantly higher with CT-P13 SC vs placebo (43.2% vs 20.8%; P < .0001).
  • CT-P13 SC was well tolerated, with no new safety signals identified.
  • The mean serum infliximab trough concentrations at weeks 14 and 54 were 13.2 and 14.8 mcg/mL with CD study and 14.6 and 16.3 with UC study, respectively.
Proportions of patients achieving co-primary and key secondary end points
at week 54 in the CD study (all randomized population)
Proportions of patients achieving primary and key secondary efficacy end
points at week 54 in the UC study (all randomized population)

Discussion:

  • “The present findings are generally comparable with or numerically better than those observed in previous clinical trials that evaluated IV infliximab in patients with CD or UC…At week 50 in the SONIC trial, 35% of patients receiving infliximab achieved corticosteroid-free clinical remission,30 compared with 40% of patients in the CT-P13 SC group in the current study.”
  • “In terms of UC, the ACT 1 study4 found that patients receiving infliximab 5 mg/kg and 10 mg/kg were more likely to achieve clinical remission based on total Mayo score after 54 weeks (34.7% and 34.4%, respectively) compared with participants receiving placebo (16.5%), and in the current study, 43.2% and 20.8% of patients, all of whom had responded to induction therapy, achieved clinical remission at week 54 in the CT-P13 SC and placebo groups, respectively.”
  • This study had a high rate of antidrug antibody detection (63.8%–65.1%)…” likely due to the use of highly sensitive, next-generation ADA assays, which have improved sensitivity compared with those used in historical studies… This suggests that route of administration of CT-P13 does not affect rates of ADA formation, and that the observed incidence of ADA is not unexpected.”
  • “The decision to initiate CT-P13 SC maintenance therapy at week 10, 4 weeks after finishing CT-P13 IV induction therapy, was based on results of PK or pharmacodynamic model simulation.”

My take: These studies suggest that SC infliximab is likely to have similar efficacy as IV infliximab

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When and How to Pursue Ileal Diversion in Crohn’s Disease

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A Simard et al. J Pediatr Gastroenterol Nutr. 2024;79:800–806. Role of ileal diversion in pediatric inflammatory bowel disease

Indications:

  • Severe, medically refractory colitis
  • Complex and medically refractory perianal disease
  • In combination with bowel resection for irreversible bowel damage (e.g., fistulae, abscesses, or strictures)

Diversion “provides the opportunity to reduce steroid use, improve growth and observe the natural history of the disease in a more controlled manner. It may also enhance quality of life”

My take: This is a handy article when considering ileal diversion in a patient with medically-refractory inflammatory bowel disease.

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Near-Death Experience from a Button Battery

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MR Smetak, LJ Wilcox. N Engl J Med 2024;391:1139. Button-Battery Ingestion

An excerpt:

A previously healthy 11-month-old girl presented to the emergency department with a 2-week history of progressively worsening dysphagia and cough..A chest radiograph showed a foreign body with a “halo” or “double-ring” sign. Approximately 10 hours after endoscopic removal, “torrential hematemesis and hemorrhagic shock developed. During emergency surgical exploration, no source of bleeding was initially identified, but intraoperative angiography revealed a fistula between the esophagus, which was dilated, and the left common carotid artery (Panel B, arrow). The artery was ligated, and hemostasis was achieved.” The patient was discharged 32 days after admission without neurologic or functional deficits.

My take: Even in children in the hospital, massive bleeding due to a coronary artery to esophagus fistula carries an extremely high mortality rate.

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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.

How to Upgrade Pancreas Care –Jay Freeman MD (Part 2)

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We had a great pancreas update lecture from Dr. Jay Freeman. In my view, a great lecture involves a well-delivered informative lecture that likely leads to an improvement in clinical practice. My notes below may contain errors in transcription and in omission. Along with my notes, I have included many of his slides.

  • Currently there are NO recommendations for medications that can prevent progression of chronic pancreatitis
  • Use of neuromodulators (eg. TCAs, Gabapentin) are often given to reduce pain
  • Cognitive behavioral therapy has been used in chronic pancreatitis with significant improvement
  • Pain management is working towards objective pain markers
  • Changes in pancreatic function are associated with risk of pancreatitis
  • CF drugs have changed pancreatic function in the CF population and may be helpful in other populations
  • Pancreatic enzymes (PERT) may decrease the risk of pancreatitis. Based on the PAUSE study, a double-blind study is needed to determine if PERT can reduce pancreatitis with ARP or CP
  • From Nationwide Children’s Summary: “The researchers found that nearly 17% of children with pancreatic-sufficient ARP and CP were treated with pancreatic enzymes. Children started on pancreatic enzyme therapy experienced fewer AP episodes annually, and approximately 40% of children on pancreatic enzyme therapy had no additional AP episodes [during a mean 2.1 years of follow-up] over approximately two years of follow-up. Children with a SPINK1 mutation and those with ARP (compared with CP) were less likely to have an AP episode after initiating pancreatic enzyme therapy… a randomized, placebo-controlled clinical trial is necessary to evaluate the true impact of pancreatic enzymes for these patients.” Freeman AJ, et al. American Journal of Gastroenterology. 2024 Apr 18. DOI: 10.14309/ajg.0000000000002772. Epub ahead of print.Open Access! Pancreatic Enzyme Use Reduces Pancreatitis Frequency in Children With Acute Recurrent or Chronic Pancreatitis: A Report From INSPPIRE. “After initiation of PERT, the mean AP annual incidence rate decreased from 3.14 down to 0.71 ( P < 0.001).”
  • The TACTIC study showed that an oral serine protease inhibitor reduced daily pain; however, the 4-week change was similar to placebo. This study shows why placebo-controlled studies are needed
  • There are other treatment approaches that are being studied in adults including antifibrotics, simvastatin, and paracalcitol

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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.

How to Upgrade Pancreas Care –Jay Freeman MD (Part 1)

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We had a great pancreas update lecture from Dr. Jay Freeman. In my view, a great lecture involves a well-delivered informative lecture that likely leads to an improvement in clinical practice. My notes below may contain errors in transcription and in omission. Along with my notes, I have included many of his slides.

  • About 10% of patients with acute pancreatitis already have damage indicating chronicity
  • Severe pancreatitis is often defined by degree of organ dysfunction (eg. cardiac, pulmonary, renal). A practical definition of severe pancreatitis in children is whether the patient requires admission to an ICU
  • The term “position paper” is typically used instead of “guidelines” due to lack of definitive data and reliance on expert opinion
  • While the guidelines suggest 1.5-2.0 x maintenance fluid volumes, the benefit of this additional IVFs is not clear. Dr. Freeman’s clinical practice is often to start with 1.5 x maintenance rate and to try to transition to enteral diet
  • Aggressive fluid resuscitation of acute pancreatitis in adults is associated with increased risk of fluid overload. Lactated ringer’s is generally fluid of choice.
  • In this study with 211 pediatric patients, starting with a narcotic increases the likelihood of continuing with narcotics. Many patients can respond to acetaminophen and NSAIDs. Using narcotics, may increase the risk of sensitization to pain (lowering pain threshold)
  • In this study with adults (Not Randomized), use of PCA was associated with longer hospitalizations, slower start to enteral nutrition and increased narcotic use at discharge
  • A single episode of acute pancreatitis, even mild cases, is associated with long-term risks including risk of exocrine pancreatic insufficiency (often transient), increased risk of diabetes mellitus and even pancreatic cancer.
  • Restricting fat in the diet for 1-2 weeks after an episode may reduce some symptoms
  • Because of risk of complications, Dr. Freeman recommends follow up after hospitalization (after a few months) and for up to 5 years (at least for 2 years)
  • Dr. Freeman indicated that he recommends checking genetic tests for pancreatitis if a patient has had more than one episode. If a patient is less than 5 years of age or has a significant family history, checking for genetic predisposition should be considered with the first bout of pancreatitis.

Key points: Even patients with acute pancreatitis need follow-up. Consider using non-narcotic medicines as the first line, especially in patients who have not ‘failed’ these medications.

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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.

Good Luck Getting Intensive Feeding Therapy

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WG Sharp et al. J Pediatr 2024; 272: 114126.Intensive Multidisciplinary Feeding Day Programs in the United States: A Report Regarding the Treatment Landscape

Key findings:

  • 16 programs met the criteria for inclusion. None of these programs were in the Western U.S. Among feeding programs that were not included, there were 16 programs excluded due to lack of an intensive day program and 1 program excluded as admissions were on hold due to transition in leadership. .
  • “Results suggest current treatment capacity of <1000 slots per year.”
  • Estimates place pediatric feeding disorders as between 1 in 23 and 1 in 37 children under the age of 5 years. Thus, if 5% needed intensive care, this would equate to ~45,000 children under age 5 yrs. This estimate does not include children >5 yrs.

The discrepancy in need (~45,000) and availability (~1000) explains why wait times can be 12 months or longer.

My take: There is a huge mismatch between supply of intensive feeding therapy programs and demand. The potential barriers include training of sufficient numbers of qualified professionals, institutional support, and reimbursement,

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Channel Islands (off California coast)

Proactive Therapeutic Drug Monitoring and Better Outcomes in Pediatric Crohn’s Disease (2024)

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S Ali et al. Clinical Gastroenterology and Hepatology, Volume 22, Issue 10, 2075 – 2083.e1. Characterization of Biologic Discontinuation Among Pediatric Patients With Crohn’s Disease

Methods:  Prospective ImproveCareNow registry data (n=823, from 7 centers) were supplemented with medical record abstraction. 

Treatment/Monitoring:

  • 86% started biologics (78% infliximab, 21% adalimumab, <1% others)
  • Twenty-six percent used concomitant immunomodulators for ≥12 months
  • Most (85%) measured TDM including 47% induction, 69% proactive, and 24% reactive

Key findings:

  • Twenty-nine percent discontinued their first biologic after median 793 days because of inefficacy (34%), anti-drug antibodies (8%), adverse events (8%), or non-adherence (12%)
  • Proactive TDM and concomitant immunomodulators were associated with 60% and 32% reduced biologic discontinuation
  • Half of patients discontinued biologics without trial of high-dose therapy and 14% without any evaluation
  • Among patients started with infliximab therapy, 62% of patients started at a dose of <6 mg/kg, 18% stared at a dose >8 mg/kg. 67% of patients underwent dose escalation. This is agreement with other studies indicating that as many as 80% of children need doses in excess of ‘standard’ dosing (5 mg/kg every 8 weeks)
  • In patients with anti-TNF medication inefficacy with TDM availability, 36% had infliximab or adalimumab levels below 5 mcg/mL. and 20% had levels between 6-8 mcg/mL.
  • Among patients who discontinued anti-TNF medications, 60% had serum trough levels less than 10 mcg/mL.
  • The rate of biologic durability was lower for those (n=61) receiving a 2nd biologic who had rates of remaining on agent of 56% at 1 yr, 28% at 2 yrs, and 10% at 4 yrs. In contrast, the first biologic had durability of 90% at 1 year, 79% at 2 years, and 66% at 4 yrs.

My take: This study strongly supports the use of proactive therapeutic drug monitoring. In addition, the authors make a compelling argument to optimize a therapy and evaluate carefully before switching to a new medication/biologic. Finally, the use of concomitant immunomodulators can improve medication durability; it is particularly important if needing to switch from one anti-TNF agent to another due to anti-drug antibodies.

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Pitt Street Bridge (Mt Pleasant, SC)

Water Beads in the News and in JPGN

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NBC News 3/20/24: New health warning issued about the dangers of water bead toys

“The absorbent polymer beads are often marketed as colorful, slimy, sensory items for kids to play with. They can be as small as a stud earring  — little enough to swallow — but grow to the size of a marble or even a golf ball when immersed in water. Once inside a child’s body, they can cause gastrointestinal blockages. The CPSC (Consumer Product Safety Commission) recorded nearly 7,000 water bead-related ingestion injuries in emergency rooms between 2018 and 2022.”

EA Pasman, MA Khan, NT Kolasinski, PT Reeves. JPGN 2024;79:752–757. Water bead injuries by children presenting to emergency departments 2013−2023: An expanding issue

CPSC issued a recall of more than 50,000 Chuckle & Roar Water Beads Activity Kits in 2023 after a 10-month-old child reportedly swallowed one of the water beads and died. (Ref: AAP News (American Academy of Pediatrics). Water bead toy kits recalled following death of 10-month-old child. Accessed Sept 21, 2024)

Methods: The authors used the National Electronic Injury Surveillance System (NEISS) to identify water bead injuries from 2013 to 2023. The nationally representative NEISS database catalogs ED encounters for injuries related to consumer products over a nationwide census and captures 500,000 injury-related encounters annually. The authors used more stringent criteria than CPSC; thus the numbers of injuries from water beads in their study are less than those reported by CPSC.

Key findings:

  • Children under age 2 years comprised 29% of injuries.
  • There was a significant uptrend in water bead injury frequency after 2020.

Discussion: Published NASPGHAN recommendations include “‘urgent’ endoscopy (<24 h from presentation, following usual NPO guidelines) for any absorptive object ingested and found to be in the stomach or small bowel. The report recommends emergent upper endoscopy for any absorptive object impacted in the esophagus causing sialorrhea.” 

My take: The database captures only a fraction of these ingestions.  These objects, even if they do not cause acute injury, could pose long-term harms due to potential carcinogenicity.

Related blog post: Foreign Bodies in Children -Expert Guidance

Why Some Children Have Problems With Antegrade Enemas

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H Pearlstein et al. JPGN 2024;79:519–524. Significance of retrograde flow with antegrade continence enemas in children with fecal incontinence and constipation

Key findings:

  • Fifty-nine (36%) antegrade contrast studies showed retrograde flow: 28/59 children (48%) were not responding adequately and 21/59 (36%) had symptoms with ACE.
  • Children with retrograde flow were more likely to have symptoms with ACE than those without (36% vs. 15%, p < 0.01). 

The authors hypothesize that symptoms, including nausea, abdominal pain, and vomiting, related to antegrade enemas are potentially similar to those experienced by patients with dumping syndrome related to the osmolar content of the flush and subsequent fluid shifts under hormonal and autonomic control.

My take: Our motility team follow most of our patients with ACEs. This study helps provide a better explanation why some children do not do well with ACEs and potential interventions.

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