Category Archives: Pediatric Gastroenterology Intestinal Disorder

IBD Briefs: Upadcitinib in Children with Severe Colitis and Timing of Infliximab Switch to SC Route in Adults

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A Yerushalmy-Feler et al. Inflammatory Bowel Diseases, 2025, 31, 3320–3326. Real-World Experience with Upadacitinib for Pediatric Acute Severe Ulcerative Colitis: An International Multicenter Retrospective Study from the Pediatric IBD Porto Group of ESPGHAN

In this study of 22 pediatric patients with ASUC refractory to infliximab, key findings:

  • By week 26, 14 (64%) were in corticosteroid-free clinical remission and 16 (73%) patients remained colectomy-free
  • Two serious AEs of an appendiceal neuroendocrine tumor and cytomegalovirus colitis

My take: It is good to see more pediatric data. The availability of upadacitinib will likely lead to lower colectomy rates.

Related blog post: IBD Briefs: Upadacitinib in Children, Predicting Crohn’s Disease, and Autoimmune Diseases Associated with IBD

L Bertani et al. Inflammatory Bowel Diseases, 2025, 31, 3363–3369. When to Switch to Subcutaneous Infliximab? The RE-WATCH Multicenter Study

Methods: The RE-WATCH study was an observational, multicenter, retrospective study performed in four IBD referral centers. Inclusion criteria meant that only patients receiving on label SC-IFX at a dosage of 120 mg every other week were included in the study. The initiation of IFX therapy as the baseline timepoint.

Key findings:

  • There were no statistical differences between the two groups, early vs. late switch, after one year in terms of the respective endoscopic response (71.4% vs 70.8%, P = .95), steroid-free clinical remission (62.5% vs 68.7%, P = .51), or IFX retention rate (75.0% vs 66.7%, P = .35).
  • There was higher endoscopic remission rates in early switch patients as compared to late switch patients; however, this trend was not significant (69.6% vs 52.1%, P = .07).
  • A return to IV-IFX was required in 1 of 43 early switch patients and in 3 of 44 late switch patients (2.3% vs 6.8%, P = .31)
  • While the early switch group appears to fare a little better, there is likely a selection bias. For example, the early group had a much lower rate of severe endoscopic score at baseline (20% vs. 54%) and lower rate of Crohn’s fistulizing disease (8% vs 33%).
partial Mayo score (pMS)
Harvey–Bradshaw index (HBI)

My take: These results indicate that outcomes are similar between patients switching from to IFX SC at both early (after induction) and late (after 6 months).

It is worth noting that prior studies have shown that home-based therapies (eg. home infusion), compared to office-based therapies, have been “associated with suboptimal outcomes including higher rates of nonadherence and discontinuation of infliximab.” This is a concern for SC biologics as well.

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Why Changing to Denmark’s Vaccine Schedule is a Bad Idea and Other Ways RFK Jr is Working to Undermine Our Health

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Last week, the following article explained why the newest changes, announced yesterday (see link below), to the vaccine schedule recommendations are not a good idea:

J Interlandi. NY Times 12/30/25: This Is the Damage Kennedy Has Done in Less Than a Year

An excerpt:

“Proponents of the push to align U.S. recommendations with those of so-called peer nations such as Denmark, Japan and Germany — all of which recommend fewer shots than the United States — have billed it as a common-sense corrective. But, as innumerable doctors and scientists have explained, when it comes to public health, countries with fewer shots on their must-have list are not actually our peers.

In Denmark, to take the administration’s favorite example, prenatal care is free and universal. More than 95 percent of pregnant women are screened for hepatitis B, and those who test positive are promptly treated and duly monitored…

None of this is true in the United States.

Here, nearly a quarter of pregnant women lack adequate prenatal care, and those who face the highest risk of contracting and spreading vaccine-preventable diseases are often the least likely to have access to doctors or pharmacies. When U.S. health officials tried to stamp out hepatitis B through vaccination programs aimed at high-risk groups, they failed miserably. It was not until they carried out a universal, at-birth vaccination policy in 1991 that hepatitis B infections finally plummeted — by about 99 percent.

In fact, if the U.S. public health system has one thing going for it relative to other nations, it’s probably vaccines. As the C.D.C.’s own data indicates, routine childhood vaccination has prevented hundreds of millions of illnesses and tens of millions of hospitalizations here. It has also saved half a trillion dollars in medical costs, a figure that jumps into the multitrillions once you factor in indirect, societal costs like lost productivity and lost wages.

The United States tends to have higher rates of measles vaccination than Europe, and fewer measles cases as a result. Compared with Denmark, we also tend to have lower hospitalization rates for rotavirus (which causes diarrhea and can be fatal in infants and children) and respiratory syncytial virus, or R.S.V. (which is a leading cause of hospitalization among children). The reason for those disparities is not in dispute: We vaccinate routinely against both viruses. Denmark does not…

In the meantime, the Food and Drug Administration is angling to make an even bigger and more enduring impact on Americans’ access to vaccines…top officials at the agency have proposed a roster of new requirements for the shots, including several that critics say would be logistically impossible and could leave us with no F.D.A.-approved Covid or flu vaccines…

We don’t have to wonder what that future will look like. We can glimpse it already in communities across the country where measles and whooping cough are resurgent and where infants and young children have already died from both. We can also see it foretold in the current flu season: This year’s flu vaccine has proved an imperfect match to the currently circulating strains. New shots, based on mRNA technology, would have one day enabled us to avoid this kind of misfire. But the nation’s leaders have imperiled that future with the decisions they made this year…

Mr. Kennedy has brought us to this precipice by aggressively subverting nearly every process and protocol that previously governed our public health institutions. He has granted political appointees enormous sway over agency scientists. He has excluded people with meaningful expertise from his planning and deliberations. And he has fired dissenters all the way up to the C.D.C. director and replaced them with lackeys, sycophants and wellness grifters.”

My take: RFK Jr and this administration has already done great damage to our health care and the toll will be evident for a long time. But, they are not done yet.

Link to yesterday’s announcement: NY Times 1/05/25: Kennedy Scales Back the Number of Vaccines Recommended for Children“Public health experts expressed outrage at the sweeping revisions, saying federal officials did not present evidence to support the changes or incorporate input from vaccine experts…and will endanger the health of children in the United States…The C.D.C.’s new schedule continues to recommend vaccines against some diseases, including measles, polio and whooping cough, for all children. Immunization against six other illnesses — hepatitis A, hepatitis B, meningococcal disease, rotavirus, influenza and respiratory syncytial virus, the leading cause of hospitalization in American infants — will be recommended for only some high-risk groups or after consultation with a health care provider.”

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Cochran Shoals, Atlanta

Duodenal Hematoma Following Endoscopy

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A Coe et al. J Pediatr Gastroenterol Nutr. 2025;81:1514–1517. Duodenal hematoma in pediatric upper endoscopy: A5‐year review and comparison to previous experience

This 5-year single-center study from 2018 to 2022 identified a total of 13 patients with duodenal hematoma (DH). There were a total of 21,569 EGDs, and 16,978 EGDs with duodenal biopsies were performed during the study period.

Key findings:

  • 1 DH in 1306 (0.08%) EGDs with duodenal biopsies. Ten of the thirteen patients had normal duodenal histology, and the other three each had findings of celiac disease, peptic duodenitis, and graft-versus host disease
  • None of the patients had a history of anticoagulant or antiplatelet agent therapy
  • Symptom onset occurred within 24 h for 8/13 (62%),48 h for 11/13 (85%), and 72 h for all 13 patients after EGD. Emesis occurred in all 13 patients and abdominal pain 7/13 (58%)
  • All patients were admitted with a mean length of stay of 18 days
  • Treatment: jejunal feedings in 4 of the 13 patients (31%), and parenteral nutrition in 10 of 13 (77%) patients. Most patients (62%) utilized opioids for pain management following DH
  • A similar study was conducted at the same center in 2015. It was noted that there was a lower rate of duodenal biopsies in the current cohort: 78.7% versus 92.4%
Computed tomography coronal image with hematoma

My take: Duodenal hematoma is a major complication leading to the need for parenteral nutrition and prolonged hospitalization. BMT and organ transplantation appear to increase this risk based on prior studies.

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Effectiveness of Switch to Subcutaneous Infliximab

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N Mathieu et al. Clin Gastroenterol Hepatol 2025; 23: 2597 – 2606. Open Access! PErsistence and Safety of Subcutaneous Infliximab 1 Year After Switch From Intravenous Route in IBD Patients in REMission

Methods: The PEREM (PErsistence, effectiveness and safety of subcutaneous infliximab after switch from intravenous infliximab in IBD patients in REMission) study, a prospective national French cohort trial, enrolled 426 patients with IBD. Participants were in steroid-free clinical remission for at least 6 months on IV-IFX when they switched to SC-IFX. 56% were on IV-IFX standard dosing (5 mg/kg 8-weekly) and 16% received combination therapy with an immunomodulator drug at baseline. All patients were switched to SC-IFX standard dosing (ie, 120 mg every other week). The treatment could be intensified during follow-up, either to 120 mg every week or 240 mg every other week.

Key Findings:

  •  At week 48, SC-IFX persistence was 95.4%
  •  86.9% of patients were in steroid-free clinical remission
  • Mean infliximab levels were 8.0 μg/mL at inclusion and 18.0 μg/mL at week 48 (P < .0001)
  • Among the 19 (4.5%) patients who stopped SC-IFX, 6 (1.4%) switched back to IV-IFX
  • 23 (5.4%) patients required SC-IFX dose escalation
  • Dosing at 10 mg/kg/Q4W had 100% SC IFX persistence compared to 95% for 5 mg/kg/Q8W; however, at the 48 week followup, there were only 6 patients in the higher dose compared to 149 in the lower dose
  • Ongoing use of combination therapy was not associated with better persistence. Though, only 7 patients were receiving combination therapy at the 48 week followup

From the discussion:

  • “The high persistence observed in the PEREM study is partly explained by the long-term control of the disease by the time of switch, the median time since last flare being over 5 years before inclusion. Henceforth, the persistence observed here is in accordance with results on long term maintenance of IV-IFX, the yearly persistence of IV-IFX without intervention being 87%.”
  • SC-IFX was associated with higher levels. However, this was expected and higher levels are needed with SC administration. The “different bioavailability of SC-IFX compared with IV-IFX is responsible for different goals of infliximab blood levels depending on its route. In particular, a level above 20 μg/mL has been associated with higher rates of remission20” with SC-IFX.

My take: This study shows that SC-IFX is a good option for patients in long-term remission. With SC-IFX therapy, more effort is needed to make sure patients are adherent with therapy and monitoring in order to achieve optimal outcomes.

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From Treatment to Cures for Autoimmune Diseases

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In March 2024, CAR-T therapy was shown to be a promising though difficult and expensive option for severe SLE (NEJM 2024; 390: 687-700. Blog post: CAR T-cell Therapy: A Cure for Autoimmune Disease?)

Eric Topol has summarized more recent advances that indicate that future treatments could be safer and less costly. Instead of manipulating T-cells outside the body, an inside the body (in vivo) approach looks promising. Substack post, 12/14/25: The Exhilarating Movement From Treatment to Cures for Autoimmune Diseases

An excerpt:

“This inside the body, off-the-shelf strategy has already been shown to be safe and successful in Phase 1 trials of refractory SLE and in patients with systemic sclerosis or severe myositis…Several companies are in clinical trials with in vivo CAR T for autoimmune diseases including Capstan Therapeutics, Kite Therapeutics, Umoja Biopharma, and Shenzhen Magic-RNA. The striking progress in this field towards universal, potential one-shot cures is tempered by residual anticipated high cost, the cytokine release syndrome and neurotoxicity that can occur with CAR T. The mRNA and non-viral vectors are considered a better choice than a lentivirus vector because of the latter’s potential risk of mutagenesis and cancer…

The Soft Reset: Inverse Vaccines to Achieve Tolerance…

Tolerogenic vaccines [are] the opposite of standard vaccines that boost the immune system…Inverse vaccines are being pursued in celiac disease (Anokion, with positive clinical trial results reported earlier this year) , multiple sclerosis (ANokion, Moderna, BioNTech), and Type 1 diabetes (Diamyd Medical), rheumatoid arthritis (Janssen clinical trials.

How Progress in Cancer Fuels Autoimmune Disease Innovation

Cancer biology is the mirror image of autoimmunity. Predisposition to cancer occurs when the immune system is hypoactive, losing its protection, whereas autoimmune disease reflects hyperactivity and a dysregulated state…The B cells are a common culprit, hence the successful use of CAR T vs B cells for both diseases. The checkpoint inhibitor PD-1 (prototype Keytruda) is to cancer (cut the brakes on the immune system) as PD-1 agonists (slam on the brakes) are to autoimmune diseases. Similarly, cancer vaccines to rev up immunotherapy are the opposite of inverse, tolerogenic vaccines…

[There is a] reciprocal relationship between CAR T for cancer and autoimmunity. What’s important to emphasize is all the work to achieve in vivo, universal CAR T works for both diseases. Anything that helps cancer immunotherapy has the big dividend of also helping the efforts for curing autoimmune diseases. The new field of structural immunotherapeutics has legs to achieve precise control of our immune system vs either sets of diseases…

We’e seeing the initial stages of a renaissance vs autoimmunity. Curing instead of just treating autoimmune diseases.”

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Long-Term Outcomes of Surgery For Excessive Drooling

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D van den Nieuwenhof, . et al. The Journal of Pediatrics, Volume 288, 114807. Open Access! Long-Term Outcomes of Surgical Drooling Treatment in Individuals with Neurodevelopmental Disabilities: A Retrospective Cohort Study

Background: “Long-term relief of drooling remains a challenge due to the side effects of anticholinergics,13 and botulinum neurotoxin type A injections provide only a temporary relief of drooling with potential loss of effect after repeated injections.15…Surgery for drooling is often considered if moderate to severe drooling persists in children after the age of 12 years.”

Submandibular duct relocation (SMDR) “is currently considered the first choice among these surgical procedures and involves the relocation of the submandibular duct papillae to the base of the tongue, allowing saliva to flow posteriorly into the oropharynx and trigger the swallowing reflex…Since the saliva is rerouted to the oropharynx, an adequate pharyngeal swallowing phase is a prerequisite for this surgery to prevent saliva aspiration and choking. Thus, SMDR is contraindicated in patients at risk of aspiration… In these cases, SMGE [submandibular gland excision] or SDL [submandibular duct ligation] can be considered.19“

Methods: This was a retrospective cohort study with 255 patients. The authors used the visual analog scale (VAS) for drooling as the primary outcome to compare the long-term treatment outcomes of submandibular duct relocation (SMDR), submandibular gland excision (SMGE), and submandibular duct ligation (SDL) for the treatment of anterior drooling in individuals with neurodevelopmental disabilities.

Key findings:

  • A mean reduction in VAS was observed of 44.9 points for SMDR (P < .001), 27.2 for SMGE (P < .001), and 25.4 for SDL (P < .001). 
  • A significant degree of drooling recurrence was observed after SDL and SMGE at long-term follow-up

    Discussion points:

    • “SMDR is an invasive treatment requiring a night of postsurgical intubation and observation in intensive care. In specifically vulnerable children, less invasive alternatives such as SDL might therefore be preferential.”
    • “Since drooling is predominantly caused by insufficient swallowing, maintaining a balance between saliva production and clearance through swallowing is essential. SMGE and SDL inhibit saliva secretion from the submandibular glands, thereby reducing the overall volume of saliva produced.19,20 However, these procedures do not actively influence the swallowing process…A durable effect after SMGE and SDL is therefore achievable only if the reduction in saliva production reaches a threshold where the volume of saliva produced matches or falls below the individual’s capacity to swallow it effectively. On the other hand, after SMDR, the swallowing frequency itself probably increases.”
    • Selection bias: “SMDR was contraindicated for patients with inadequate swallowing… leads to a selection of less vulnerable patients with more favorable characteristics to undergo the SMDR procedure.” Thus, the improved results from SMDR over the other techniques is likely related to selection bias, though the authors adjusted the analysis “for differences in cognitive and oral motor functioning.”

    My take: Excessive drooling is a common problem in children with neurodevelopmental disabilities. This study provides useful data on surgical management.

    Video Capsule Endoscopy in VEO-IBD — Is the Juice Worth the Squeeze?

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    S-I Hagiwara et al.  Inflammatory Bowel Diseases, 2025; izaf144, https://doi.org/10.1093/ibd/izaf144. Open Access! Feasibility and Safety of Small Bowel Capsule Endoscopy in Very Early-Onset Inflammatory Bowel Disease: A Multi-Institutional Study

    This article shows that video capsule endoscopy (VCE) (aka small bowel capsule endoscopy [SBCE]) is feasible in children with very early-onset inflammatory bowel disease (VEO-IBD). There were 82 patients (median age, 3.8 years; median body weight, 13.0 kg) who underwent 104 SBCEs. All capsules were deployed endoscopically. Gastrointestinal patency was assessed in 95% of procedures, most commonly using patency capsules (70%).

    Key findings:

    • Observation of the entire small intestine was achieved in 100 (96.1%) patients
    • Of the remaining 4 patients, 3 could not undergo a complete observation of the entire small intestine due to battery depletion, and 1 had the capsule retained in the stomach
    • Abnormal small bowel findings were observed in 42% of patients, with aphthae being the most common (34%), followed by ulcers (18%)

    In their discussion, the authors note that due to young age, the capsules and the patency capsules required endoscopic deployment (best in duodenum). Thus, most patients received general anesthesia or intravenous sedation twice within a short period.

    The authors note that “SBCE has been reported to be superior to MRE in detecting superficial mucosal activity… [and] offers a radiation-free, relatively well-tolerated, and highly sensitive method for mucosal evaluation in VEO-IBD.”

    My take: Given the typical use of a patency capsule and thus the need for two separate anesthesia dates, I doubt the “juice is worth the squeeze” in utilizing SBCE for most patients VEO-IBD.

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    Useful repurposing of phone booth in Cotwolds, UK

    Genetic Risk Assessment and Testing for Gastrointestinal Cancers and Polyposis (2025)

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    K Monahan et al. Gastroenterol 2025; 169: 1147-1165. Open Access! In Our Scope of Practice: Genetic Risk Assessment and Testing for Gastrointestinal Cancers and Polyposis in Gastroenterology

    This open access review is a great up-to-date reference/resource on risks, evaluation/surveillance, and genetic testing in a wide range of disorders. This includes the myriad of polyposis syndromes as well as colorectal cancer, pancreatic cancer, and gastric cancer.

    Table 2 describes the Genetic Syndromes Associated With Risks for GI Cancers and Polyposis and the recommended surveillance/testing. For example –FAP (familial adenomatous polyposis) and JPS (juvenile polyposis syndrome):

    “Yield of MGPT in GI cancers and polyposis. MGPT has been evaluated in a number of GI cancers/polyposis. Shown in this figure are rates of positive findings on MGPT. Some of the variability among studies could be attributed to the number of genes included on the panels. [As an example,] among CRC patients, 9.9%–15% of cases were found to carry pathogenic variants in cancer-related genes.62,65,66“

    One recent new twist is the availability of direct-to-consumer testing (DTC). “Caution is advised as DTC tests can vary with regard to their quality and clinical validity. For example, some nonclinical DTC genetic tests use arrays (or “chips”) to detect single nucleotide polymorphisms associated with cancer risk in genome-wide association studies, and do not perform comprehensive sequencing of the genes of interest or evaluate for genomic deletions or duplications. DTC testing may focus on selected high-risk variants and thus incomplete test results could be falsely reassuring.

    Furthermore, DTC tests do not usually include pre- and post-test genetic counselling to inform individuals about the genomic information being evaluated, as well as the broad implications for them as an individual, and for their families.”

    My take: This article provides useful updated guidance on genetic testing for a wide range of GI disorders that predispose to cancer.

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    Is Surveillance Helpful For Patients with Barrett’s Esophagus?

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    Key finding: Compared with at need endoscopy, 2-yearly surveillance costs $115,563/QALY
    gained.

    Related editorial: SN Van Munster et al. Gastroenterol; 2025: 169: 1116 – 1118. Open Access! Endoscopic Surveillance for Nondysplastic Barrett’s Esophagus: Are We Violating “Primum Non Nocere”?

    “Although guidelines have historically endorsed surveillance, this endorsement has rested on observational studies vulnerable to bias and confounding. The first RCT now available provides no evidence that routine surveillance improves survival or decreases cancer burden. These findings align with an expanding body of prospective cohort evidence suggesting that the annual progression rate from NDBE to EAC [Non-Dysplastic Barrett’s Esophagus to Esophageal Adenocarcinoma] is substantially lower than historically believed—approximately 0.3%–0.5% per year,8–10,13,14 as opposed to the 2.0%–4.0% per year estimated in the early 1990s.15–17“

    The authors note that recent Dutch guidelines have been revised: “Routine surveillance is no longer recommended for low-risk Barrett’s patients—defined as those with segments with a maximal extent (Prague M) of <5 cm and no prior dysplasia.”

    My take: While Barrett’s esophagus is a rare issue for pediatric gastroenterologists, it is worth noting that these recent studies cast doubt on the benefit of routine surveillance endoscopy in patients with nondysplastic Barrett’s esophagus.

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    Postoperative Outcomes with Tofacitinib Following Colectomy for ASUC and Real-World Outcomes for Upadacitinib in Crohn’s Disease

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    C Larson et al. Clin Gastroenterol Hepatol 2025; 23: 2263-2271. Postoperative Outcomes in Tofacitinib-Treated Patients With Acute Severe Ulcerative Colitis Undergoing Colectomy

    This  was a multicenter, retrospective, case-control study of patients hospitalized with ASUC who underwent colectomy, comparing patients treated with tofacitinib (n=41) prior to colectomy with infliximab-treated controls (n=68).

    Key findings:

    • Compared with tofacitinib-treated patients, infliximab-treated patients had higher overall rates of overall (44 [64.7%] vs 13 [31.7%]; P = .002) and serious (19 [27.9%] vs 3 [12%]; P = .019) postoperative complications

    My take: This study supports the safety of JAK inhibitor therapy for ASUC. It showed a significantly lower rate of overall postoperative complications in ASUC patients treated with tofacitinib compared with infliximab; the authors note that “these findings can likely be extrapolated to upadacitinib, a selective JAK inhibitor, given its similar mechanism of action.”

    J Devi et al. Clin Gastroenterol Hepatol 2025; 23: 2281-2291. Open Access! Real-World Effectiveness and Safety of Upadacitinib in Crohn’s Disease: A Multicenter Study

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