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.

Related blog posts:

• Most Kids with Rumination Respond to Specialized Treatment
• Internet Survey: Lots of People Have Rumination
• Expert Advice for Diagnosis and Treatment of Rumination Syndrome
• The Half Empty Glass: Rumination Outcomes
• High-resolution Esophageal Manometry for Rumination Syndrome.
• Costs of Rumination (You don’t have to be Vinny Gambini to make the diagnosis)
• Jose Garza: What’s New in Motility (Part 2)
• Jose Garza: What’s New in Motility (Part 1)

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.
  

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

Related blog posts:

• Vedolizumab and Infliximab: Expected Dosing When Switching From IV to SC Routes
• SC Infliximab versus Vedolizumab for Crohn’s Disease and for Ulcerative Colitis
• REMSWITCH: Infliximab IV to SC Study
• FDA-Approved Subcutaneous Infliximab (Zymfentra) Now Available
• Infliximab Injections Coming Soon

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.

Related blog posts:

• Case report: Spondylodiscitis After Button Battery Ingestion
• Foreign Bodies in Children -Expert Guidance Even with “spent” batteries, there is enough residual charge to cause injury and all ingestions (even if asymptomatic) into the esophagus require emergent removal. If these batteries are in the stomach & asymptomatic, urgent removal is recommended if age < 5 years and BB ≥20 mm.
• Mitigation Efforts for Button Batteries (also includes case report of aorto-esophageal fistula and emergency surgery 25 days after ingestion of a button battery)
• New Button Battery Guidelines -with honey and vinegar
• Button battery -Update For Families
• Do Button Battery Guidelines Need To Be Revised?

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