ACupuncTure for Irritable bOwel syNdrome (ACTION)

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J-W Yang et al. Gastroenterology, Volume 169, Issue 5, 958 – 969.e5. Open Acces! Efficacy of ACupuncTure in Irritable bOwel syNdrome (ACTION): A Multicenter Randomized Controlled Trial

This ACTION study enrolled 280 patients (18-75 yrs) with IBS-D in a multicenter randomized controlled trial in 6 hospitals in China. “For the sham acupuncture group, blunt-tipped placebo needles with a similar appearance to real needles were used over the adhesive pads with no skin penetration. Five fixed pairs of non-acupoints (10 stimulation points in total) away from meridians or conventional acupoints were used.”

Key finding:

  • The primary outcome (see below) was reached by 71 (57.9%) patients in the acupuncture group compared with 47 (41.4%) patients in the sham acupuncture group (risk ratio 1.40; P = .008)
  • The effects of acupuncture in symptomatic improvements of IBS-D persisted 3 months after treatment with minimal to no side effects
  • Limitations including the difficulty of acupuncture blinding (despite the identical treatment setups)

My take: Acupuncture, especially given its safety, is a reasonable therapy for IBS-D; though, it is not recommended in recent pediatric guidelines. “The rub” in many locations is finding qualified practitioners.

Related blog posts:

Dr. B Li: Cyclic Vomiting Syndrome 2025

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Dr. B Li, emeritus professor of Pediatrics (Medical College of Wisconsin), gave this year’s Billy Meyers Lecture. Dr. Li is considered the world’s foremost authority on cyclic vomiting syndrome (CVS) (‘the emperor of emesis’). He gave a fantastic update.  I have taken some notes and shared many of his slides. There may be inadvertent omissions and mistakes in my notes. More information on the CVS 2025 guidelines is noted in a separate post: 2025 Pediatric Cyclic Vomiting Syndrome Guidelines

  • Historical background of CVS: Early descriptions of CVS date back to 1880s and Samuel Gee (who also is credited with the first modern description of celiac disease). Charles Darwin was likely affected by CVS
  • Epidemiology: CVS is not a rare disorder. It likely affects ~2% of kids and adults
  • There are several patterns of CVS. Many patients who have CVS do not have a cyclical pattern
  • Lethargy and pallor are common symptoms which make patients appear more ill
  • Retching on an empty stomach and severe emesis are hallmarks and likely indicate that the primary mechanism is not due to the GI tract. Though there are some food poisonings (eg. Bacillus cereus) that can have some of these symptoms but typically milder in severity
  • Previously, CVS patients were thought to be well in between episodes. However, ~40% have inter-episode symptoms
  • Quality of life is correlated mainly with anxiety/coping rather than the severity of episodes
  • Children with CVS often (~75%) develop migraines by adulthood
  • Underlying pathophysiology likely involves the autonomic nervous system
  • 2025 CVS Guidelines — took about 3 years to develop. It is noted that the 2008 guideline diagnostic criteria missed about 48% of cases (Bujarska et al. JPGN 2025; 80: 417)
  • 2025 Guidelines emphasize limited diagnostic workup at presentation (eg. UGI and basic labs) unless there are alarm symptoms. Alarm symptoms include the following:
  • For abortive therapy, the new guidelines favor aprepitant over ondansetron, and generally favor D5 over D10 IVFs.
  • For prophylactic therapy, there is now an emphasis on non-pharmacologic therapy in addition to pharmacologic agents and PENFS. Propranolol and aprepitant are favored prior to use of TCA agents like amitriptyline due to side effect profile
  • Action plan for ED may help speed care and lower likelihood of admission
  • PENFS for prophylactic therapy had a durable response (113 days) in a recent study
  • Cannaboid hyperemesis syndrome (CHS) was first described in 2004 and has been rapidly increasing related to increased use and potency of THC products. Haloperidol, topical capsaicin and hot water (prolonged) bathing are often effective
Variants include the CVS associated with mitochondrial dysfunction, the Sato variant associated with increased BP, increase ACTH/cortisol, Catmaenial CVS is related to menses, and CHS (CVS-like) associated with cannabis use

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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

Understanding the Ileal Pouch in Inflammatory Bowel Disease and Familial Adenomatous Polyposis

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A Phillip et al. J Pediatr Gastroenterol Nutr. 2025;81:913–921. A narrative review of the ileal pouch in pediatric inflammatory bowel disease and familial adenomatous polyposis

Introduction: Total proctocolectomy with ileal pouch-anal anastomosis (IPAA) can be a life changing solution for a subset of pediatric inflammatory bowel disease (IBD) and familial adenomatous polyposis (FAP) patients. For patients with severe disease a three-stage approach is commonly performed.

Creation of IPAA -Three Stages:

Endoscopic Images and IPAA Anatomy:

  • The article provides guidance on complications including pouchitis, CD-like inflammation of the pouch, J-pouch failure, fertility after IPAA along with follow-up/screening recommendations.
  • As for screening, adult guidelines recommend annual screening for IBD patients with high risk features—previous dysplasia, primary sclerosing cholangitis, type C mucosa, refractory pouchitis. In those without these features, guidelines are variable, with one suggesting screening every 5 years. In FAP patients, the recommendation for surveillance screening following IPAA is pouchoscopy every 1–2 years.8

My take: Most pediatric gastroenterologists are not proficient in pouch management due to the small number of our patients needing IPAA. This review provides a terrific review/resource.

Related blog posts:

A Medical Wolf in Sheep’s Clothing – Monogenetic Diseases Not So Rare

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F Rahimov et al. NEJM 2025; 393: 1589-1598. Common Diseases in Clinical Cohorts — Not Always What They Seem

This was a two-part study. First the authors examined the frequency of monogenetic rare diseases among patients with primary diagnosis of multiple sclerosis, inflammatory bowel disease (IBD), or atopic dermatitis using the UK Biobank. The UK Biobank is a prospective cohort with >500,000 participants.

In the second part of the study, the authors examined populations with these diseases who had participated in clinical trials. For IBD, the authors utilized five (phase 3) clinical trials includingthe two SERENE trials (SERENE CD, SERENE UC) which examined the use of adalimumab, two risankizumab trials, and one trial of upadacitinib. In total, exome sequencing was performed in 580 with Crohn’s disease and 900 with ulcerative colitis.

This summary of this article focuses on the findings relative to IBD.

Key findings:

  • In the UK Biobank a diagnosis of a rare monogenetic disease was identified in 53 of 1850 (2.86%) with multiple sclerosis, 75 of 6681 (1.12%) with a diagnosis of inflammatory bowel disease, and 25 of 998 (2.50%) with a diagnosis of atopic dermatitis
  • Among 1480 clinical trial IBD participants with sequencing data, the authors identified 70 (4.73%) who had a molecular diagnosis of a rare disease 
  • Patients with rare clinical variants responded poorly to medical treatments. For example, in the SERENE-adalimumab studies, 31 of 33 (94%) did not have clinical or endoscopic remission within a year

Discussion Points:

  • “It is estimated that collectively 4 to 6% of the general population are affected by some form of a rare disease.37” In the absence of routine exome sequencing, diagnosing rare diseases has been a lengthy and difficult process 
  • “The higher fraction of rare diseases identified in the clinical trials cohort (4.73%) than in the U.K. Biobank cohort (1.12%) may be attributed to the targeted recruitment of patients with moderate-to-severe inflammatory bowel disease“
  • TNFRSF13B was the most common pathogenetic variant in both the Biobank group (25 of 75) and the trials cohort (39 of 70). This variant causes common variable immunodeficiency and “is probably misdiagnosed as inflammatory bowel disease or primarily manifests with inflammatory bowel disease–like symptoms.”
  • “Rare disease–associated genes may offer insights into potential mechanisms of nonresponse, as we found in this study, and may help in the identification of novel therapeutic targets for inflammatory bowel disease. Conversely, some patients with rare diseases could present opportunities for drug repurposing when they have a serendipitous response to treatments in clinical trials.”

My take:

  1. This study shows that misdiagnosis of rare disease as common conditions is not infrequent.
  2. If the trial IBD population had enrolled young children, the frequency of rare monogenetic diseases would have been higher and captured a wider variety of disorders.
  3. For IBD, use of exome sequencing is widely recommended in those with very early onset disease and is a good idea in those with unusual features and in those who are not responding favorably to treatment.

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From Chalktoberfest 2025

Dr. Jennifer Lee: AI for Peds GI

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Recently, Dr. Jennifer Lee gave our group an excellent update on artificial intelligence (AI) for pediatric gastroenterology.  My notes below may contain errors in transcription and in omission.

  • AI is ubiquitous -it helps you login into your phone, helps with traffic apps, filters spam from email, and even edits Bowel Sounds (gets rid of the ‘umms’)
  • AI can help and AI can harm
  • Dr. Lee thinks that AI is not going to replace doctors and may help doctors in their clinical work
  • AI is teaching computers to think and predict problems. This can include analyzing radiology images, endoscopic findings (eg. polyps), interpreting EKGs, help with voice recognition, and scribe office visits (still in early stages)
  • For EoE, it was hypothesized that PPI-REE was different than EoE. However, it turned out that no significant differences were found. Thus, diagnosis of EoE no longer requires exclusion of EoE. (Related blog posts: Do We Still Need PPI-REE?, Updated Consensus Guidelines for Eosinophilic Esophagitis)
  • For colonoscopy, AI may aid polyp detection but whether this is clinically meaningful is unclear
  • With more complex analysis, AI is less transparent
  • AI algorithms can increase bias
  • Reliance on AI could lead to skill deterioration. MIT did a study showing less brain activity when using ChatGPT
  • Generative AI can create a summary of a patient chart. EHRs are partnering with AI
  • Agentic AI is when AI is set up to act autonomously like reminding patients to get vaccines, reminding to make appointments, or helping schedule appointments
  • AI in the clinic and hospital may help reduce documentation burden, improve satisfaction and improve safety for patients
  • AI does have a problem of hallucination (‘making stuff up’) (my comment: so can people). Case report of man admitted to the hospital after following ChatGPT advice in substituting sodium bromide to reduce salt intake (Eichenberger et al. Annal Internal Medicine, 2025. A Case of Bromism Influenced by Use of Artificial Intelligence)
  • AI tools are still in early stages; however, ChatGPT uptake has been much quicker than previous internet tools

Related blog posts:

Related article: A Soroush et al. Clin Gastroenterol Hepatol 2025; 23: 1472-1476. Impact of Artificial Intelligence on the Gastroenterology Workforce and Practice

Randomized Control Trial of the Modified Crohn’s Disease Exclusion Diet (CDED)

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RS Boneh et al. Clin Gastroenterol Hepatol 2025; 23: 2001-2011. Open Access! Modified Crohn’s Disease Exclusion Diet Maintains Remission in Pediatric Crohn’s Disease: Randomized Controlled Trial

In this “DIETOMICS” study with 56 children with mild-to-severe Crohn’s disease, after a 2 week exclusive enteral nutrition (EEN) diet, 30 patients were randomized to CDED and 26 to EEN.

Diet intervention: The CDED group followed 3 diet phases over 24 weeks: phase 1 (weeks 3–8) supplemented with 50% PEN; phase 2 (weeks 9–14) with 25% PEN, as described previously16; and phase 3 (weeks 15–24) with gradual introduction of more foods, including 1 and 2 free meals per week from weeks 15 and 18, respectively.17 Patients in EEN group received 8 weeks of EEN followed by gradual introduction of free diet with 25% PEN up to week 24.

Key findings:

This study with a relatively small number of enrolled patients had a lot of variables in dietary parameters. “An additional potential confounder in this study is the use of IMM therapy. Although both groups were recommended to initiate IMM therapy from weeks 4 to 5 to maintain remission, several CDED patients opted for monotherapy with CDED and preferred to delay medication initiation. Interestingly, 90% of patients on CDED without IMM therapy were in remission at week 14 and 100% were in remission at week 2” (possibly impacting decision not to use IMM).

My take: This study adds another piece of information to the puzzle on dietary therapy for Crohn’s disease. The authors note the following: “while CDED shows promise as a standalone therapy in some cases, in more severe cases it may be more appropriately as an adjuvant to top-down treatment with early anti-TNF.4 Recent research and guidelines advocate for a top-down approach (anti-TNF ± nutrition) for more severe disease, emphasizing the integration of anti-TNF therapy with nutrition.8,29 This approach is crucial during critical growth stages, as the conventional step-up method may lead to ineffective use of IMM with prolonged steroid exposure and growth issues.12“

Related blog posts:

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

FDA Approves Higher Dosage of Linaclotide for IBS-C and ByHeart Formula Recall Due to Botulinism

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A Brooks. HCPLive 11/5/25: FDA Approves Linaclotide (Linzess) Capsules for Pediatric IBS-C

An excerpt:

The US Food and Drug Administration (FDA)  has approved Ironwood Pharmaceuticals’ linaclotide (Linzess) capsules for pediatric patients ≥ 7 years of age with irritable bowel syndrome with constipation (IBS-C), making it the first treatment approved for IBS-C in this patient population.1…

The approval for pediatric IBS-C was supported by extrapolation of efficacy from adequate and well-controlled studies in adults and a 12-week double-blind, randomized, parallel-group trial in pediatric patients 7-17 years of age who met modified Rome III criteria for child/adolescent IBS-C. The recommended dosage for this indication is 145 mcg orally once daily.1…

In 2023, the FDA approved linaclotide for the treatment of pediatric patients aged 6-17 years with functional constipation at a recommended dosage of 72 mcg orally once daily. 

Reference: US Food and Drug Administration. FDA approves 1st drug for children 7 years and older with irritable bowel syndrome with constipation. November 5, 2025. Accessed November 5, 2025. https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-1st-drug-children-7-years-and-older-irritable-bowel-syndrome-constipation

Also, NBC news (11/08/25): ByHeart baby formula recalled amid 10-state outbreak of infant botulism The U.S. Food and Drug Administration said the outbreak includes 13 hospitalizations since August of children who consumed ByHeart Whole Nutrition Infant Formula. No deaths have been reported.

The recall includes two lots of the powdered formula with Dec. 1 “use by” dates, the FDA said in a statement Saturday. The lot numbers are 206VABP/251261P2 and 206VABP/251131P2…The FDA says ByHeart makes up less than 1% of the baby formula sold in the U.S.

Chicago Botanic Garden

Proximal Ileal Crohn’s Disease is Harder to Treat

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K Takenaka et al. Clin Gastroenterol Hepatol 2025; 23: 1991-2000. Open Access! Inadequate Efficacy of Biologics for Treating Proximal Ileal Lesions in Crohn’s Disease: A Prospective Multicenter Study

This multicenter prospective study (n=253) examined efficacy of treatment in patients with proximal ileal disease using balloon-assisted enteroscopy (BAE). The recruited patients had a mean disease duration of 4 years. 52% were naive to biologic treatment at baseline.

Key findings:

  • At baseline, 74 patients (29.2%) had proximal ileal ulcerations without terminal ileal ulcerations
  • At week 26, after treatment with anti-TNF therapy (n=103), ustekinumab (n=99) or vedolizumab (n=51), endoscopic remission was achieved in 91 patients (36.0%). Of the patients with complete ulcer healing of the terminal ileum, 28.6% (22/77) had residual ulcers in the proximal ileum
  • The rate of endoscopic remission in the proximal ileum (50.9%) was relatively lower compared with the colon (63.4%) and terminal ileum (56.7%)
  • After a median follow-up of 134 weeks, residual ulcerations in the proximal ileum were associated with a poorer prognosis (P = .0126 for hospitalization and P = .0014 for surgery). In contrast, there was no significant differences in hospitalization and surgery associated with endoscopic activity vs remission in the colon or terminal ileum.

Discussion: Residual “proximal ileal ulcerations … are associated with a poorer prognosis…Additionally, we confirmed that proximal ileal inflammation is less responsive to biologic therapies compared with colonic inflammation. Although the reasons for this disparity remain unclear”

My take: Balloon-assisted enteroscopy is not frequently used in the setting of inflammatory bowel disease, particularly in pediatrics. MRE is typically used to follow proximal small bowel disease, though it has less sensitivity for luminal mucosal disease.

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Hypercoagulation with Acute Severe Ulcerative Colitis (ASUC) Persists for Months

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BJ Griffiths et al. Clin Gastroenterol Hepatol 2025; 23: 1798-1807. Open Access (PDF)! Hypercoagulation After Hospital Discharge in Acute Severe Ulcerative Colitis: A Prospective Study

Methods: In this prospective study, twenty-seven adult patients with ASUC and 25 control patients with quiescent ulcerative colitis were recruited. Thrombin generation (endogenous thrombin potential), rotational thromboelastometry (EXTEM and FIBTEM maximum clot firmness), procoagulant factors, anticoagulant factors, and fibrinolytic markers were assessed for those with ASUC on admission (Day 1), Day 5, 4 weeks, and at 8–12 weeks. These assessments were performed on a single occasion for control patients.

Key findings:

Discussion:

  • “Patients with ASUC had a hypercoagulable profile on initial presentation to the hospital, before receipt of LMWH, which was consistently demonstrated by individual and global assays of coagulation. The most marked elevations of individual factors at presentation were seen in the levels of Clauss fibrinogen, platelets, VWF, and FVIII, alongside heightened
    levels of the inhibitors of fibrinolysis PAI-1 and TAFIa.”
  • “This hypercoagulable state persisted for many weeks after hospital discharge, with levels of FVIII, fibrinogen, VWF, and inhibitors of fibrinolysis (TAFIa) remained significantly elevated at all timepoints up to 12 weeks, compared with the control population. This is despite
    intensive treatment for ASUC in all patients.”
  • “VTE and pulmonary embolism are 1 of the leading causes of morbidity and mortality during IBD flare-ups. The findings from this study reinforce the importance of thromboprophylaxis administration to all patients with ASUC at first presentation to hospital.”

My take: This study is in adults; the risk of VTE is lower in children and guidance on VTE prophylaxis is not clear.

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Dupilumab for FPIES

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M Plassmeyer et al. Journal of Allergy and Clinical Immunology 2025; Dupilumab Opens a Therapeutic Window in Food Protein Induced Enterocolitis Syndrome by un-licensing dendritic cells

Thanks for Ben Enav for this reference.

Methods: This was a two-part study: “(i) a detailed single-patient case of wheat-triggered, endoscopy-confirmed colitic FPIES treated with dupilumab 300 mg subcutaneously every two weeks and (ii) a prospective follow-up of seven additional FPIES patients all of whom initiated dupilumab for approved comorbidities. Serial flow cytometry quantified dendritic-cell OX40L and CD8+ CRTH2+ T-cell subsets before and after treatment; open food challenges assessed clinical tolerance.”

Key Findings:

  • Index case: Within two injections of dupilumab, the wheat sensitive patient tolerated a 50 g wheat protein challenge without gastrointestinal symptoms—this was the first uneventful exposure in 20 years. Discontinuation of dupilumab led to relapse; re-initiation again restored clinical tolerance
  • Cohort: All seven additional patients (ages 2–58 yr; triggers: milk, soy, rice, wheat, shellfish) achieved unrestricted dietary tolerance within three months
  • An important finding in the index case as well as the follow up cohort is the dupilumab induced drop in dendritic cell OX40L. OX40L is a TNF-superfamily co-stimulatory molecule induced on dendritic cells and other antigen-presenting cells.

My take: Dupilumab appears to be a promising medication for FPIES and warrants further study. If confirmed to be effective, it is likely to be targeted to those with approved comorbidities and those with more severe presentations.

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Amicalola Falls State Park