ACCURE Trial: Appendectomy As an Adjunct Ulcerative Colitis Treatment Plus One

Posted on May 6, 2025 by gutsandgrowth

YIZ Acherman, et al. The Lancet Gastroenterology & Hepatology, 2025. DOI: 10.1016/S2468-1253(25)00026-3. Open access! Appendicectomy plus standard medical therapy versus standard medical therapy alone for maintenance of remission in ulcerative colitis (ACCURE): a pragmatic, open-label, international, randomised trial

Background: “An inverse association between appendicectomy and the development of ulcerative colitis was first reported in 1987, with subsequent case-control studies confirming this observation, and suggesting a possible role of the appendix in ulcerative colitis. In 2016, our research group did a systematic review and meta-analysis of available (case-control) studies. This analysis showed that previous appendicectomy was associated with a significantly reduced risk of developing ulcerative colitis, with an overall odds ratio of 0·39 (95% CI 0·29–0·52).”

Methods: Adult patients (n=197) with established ulcerative colitis who were in remission but had been treated for disease relapse within the preceding 12 months were randomly assigned (1:1) to undergo appendicectomy plus continued maintenance medical therapy (intervention group) or to continue maintenance medical therapy alone (control group). Approximately 25% of participants had pancolitis.

Key findings:

The 1-year relapse rate was significantly lower in the appendicectomy group than in the control group (36 [36%] of 99 patients vs 55 [56%] of 98 patients; relative risk 0·65 [p=0·005; adjusted p=0·002).

My take (borrowed from the authors): “The ACCURE trial is the first randomised controlled trial evaluating the clinical effectiveness of appendicectomy in maintaining remission in patients with ulcerative colitis without advanced medical therapy (ie, biologicals or small molecules). This trial shows that laparoscopic appendicectomy, in addition to standard medical therapy, significantly reduces the relapse rates within 1 year.”

Also, NPR notes 5/5/25: NIH cuts baby ‘Safe to Sleep’ team. Here’s what parents should know

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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.

Targeting Intestinal Epithelial Serotonin for Treating Disorders of Gut-Brain Interaction and Mood

Posted on May 5, 2025 by gutsandgrowth

Briefly noted: LY Hung et al. Gastroenterol 2025; 168: 754-768. Open Access! Intestinal Epithelial Serotonin as a Novel Target for Treating Disorders of Gut-Brain Interaction and Mood

This study used transgenic, surgical, and pharmacological approaches to study the effects of intestinal epithelial serotonin reuptake transporter or serotonin on mood and gastrointestinal function, as well as relevant communication pathways.

Key findings:

Serotonin reuptake transporter ablation targeted to the intestinal epithelium promoted anxiolytic and antidepressive-like effects without causing adverse effects on the gastrointestinal tract or brain; conversely, epithelial serotonin synthesis inhibition increased anxiety and depression-like behaviors.
In utero SSRI exposure is a significant and specific risk factor for development of the DGBI, functional constipation, in the first year of life.

My take: While this lengthy article presents data mainly from mice studies, it further supports the likelihood that SSRI selective targeting of the gut epithelium may improve anxiety, depression and comorbid DGBI. Selective targeting of the GI tract would reduce adverse effects of these medications.

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Menetrier’s Disease in a Pediatric Patient Plus Measles and Influenza Updates

Posted on May 4, 2025 by gutsandgrowth

X Wang et al. N Engl J Med 2025;392:1334. Ménétrier’s Disease

History: 16-year-old girl was admitted to the hospital with a 2-month history of leg swelling and hypoalbuminemia. She had no gastrointestinal symptoms.
Treatment: She was placed on a high-protein diet and medications to eradicate a concurrent infection with Helicobacter pylori. At a 3-month follow-up visit, the patient’s edema and hypoalbuminemia had resolved.

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Measles as of Friday May 2nd (per Caitlin Rivers): “According to CDC, a total of 935 confirmed measles cases have been reported by 30 jurisdictions. The previous high was 1,274 in 2019. So far this year, 121 cases (13%) have been hospitalized.”

AP News May 2nd: CDC reports 216 child deaths this flu season, the most in 15 years

“More U.S. children have died this flu season than at any time since the swine flu pandemic 15 years ago, according to a federal report released Friday…It’s a startlingly high number, given that the flu season is still going on. The final pediatric death tally for the 2023-2024 flu season wasn’t counted until autumn…There are likely several contributors to this season’s severity, but a big one is that fewer children are getting flu shots, added O’Leary, a University of Colorado pediatric infectious diseases specialist. The flu vaccination rate for U.S. children has plummeted from about 64% five years ago to 49% this season. Flu vaccinations may not prevent people from coming down with symptoms, but research shows they are highly effective at preventing hospitalizations and deaths, O’Leary said.”

Long-Acting GLP-2 Analogue Glepaglutide Reduces Parenteral Support

Posted on May 2, 2025 by gutsandgrowth

PB Jeppesen et al. Gastroenterol 2025; 168: 701-713. Open Access! Glepaglutide, a Long-Acting Glucagon-like Peptide-2 Analogue, Reduces Parenteral Support in Patients With Short Bowel Syndrome: A Phase 3 Randomized Controlled Trial

Background: “GLP-2 is a specific, endogenous, intestinal, pro-adaptive factor that plays a key role in enhancing intestinal mucosal morphology, function, and integrity under normal and pathophysiological conditions. The introduction of GLP-2 analogue treatment has been a paradigm shift in the treatment of SBS, targeting the pathophysiology of SBS by aiming to reinforce the structural and functional integrity of the remaining intestine. Exogenous GLP-2 induces significant hyperplasia of the small intestinal mucosal epithelium via stimulation of stem cell proliferation in the crypts and via inhibition of apoptosis in the villi…

The short half-life of 5–7 minutes for circulating native GLP-2³² is a significant practical limitation for its use in a therapeutic setting. This is improved for the currently marketed GLP-2 analogue teduglutide, which has a half-life in circulation of approximately 2 hours.³³ However, treatment is time-consuming due to the requirement for daily drug product reconstitution and dosing…

Glepaglutide is a novel, long-acting GLP-2 analogue in a stable, aqueous formulation for subcutaneous administration to treat patients with SBS. The stability in aqueous solution allows for dosing of glepaglutide as a ready-to-use liquid formulation. The mean effective half-life is 88 hours,³⁴ which enables extension of the dosing interval beyond daily dosing.”

Methods: In this placebo-controlled, randomized, parallel-group, double-blind, phase 3 trial, adult patients (n=106) with SBS with intestinal failure requiring PS ≥3 d/wk were randomized 1:1:1 to 24 weeks of glepaglutide 10 mg twice weekly or once weekly or placebo

Key findings:

Glepaglutide twice weekly significantly reduced weekly PS volumes from baseline to week 24 vs placebo (mean change, −5.13 vs −2.85 L/wk; P = .0039; primary end point).
The improvement with glepaglutide was more prominent in those without a colon in continuity.
Mean concentrations of citrulline (a biomarker for enterocyte mass) increase 47% and 19% from baseline in the TW and OW treatment groups vs 5% in the placebo group
Serious adverse events were more common in both glepaglutide groups (28.6% and 11.4% for TW and OW respectively) compared to 5.6% for placebo. Specific risks of the active treatment included injection site reactions (common). Stoma complications (swelling of stoma nipple) along with GI events (nausea, vomiting and pain) were reported in more than 10% of patients. One patient developed cholecystitis and one developed a generalized rash in the active treatment group.
61 of 70 patients (87%) treated with glepaglutide developed anti-drug antibodies. However, the authors found no apparent association with glepaglutide pharmacokinetics.

The improvement in parenteral support was more notable in those without the colon in continuity

Difference compared to placebo: 14.1% more of patients receiving twice weekly dosing and 11.2% more of patients receiving once weekly dosing of glepaglutide achieved enteral autonomy.

My take: This study shows that glepaglutide, like its GLP-2 analogue predecessor teduglutide, reduces the volume of parenteral support for patients with SBS. Due to its longer half-life, less frequent dosing is an added benefit compared to teduglutide.

Drawbacks for this group of medications include the potential for long-term adverse effects, endoscopic monitoring (possibly both upper endoscopy and colonoscopy), substantial costs, and reversion of intestinal failure severity when the medications are stopped.

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Elevated Fecal Calprotectin Levels in Pediatric Patients with H pylori Infection

Posted on May 1, 2025 by gutsandgrowth

P Villalba-Davila et al. J Pediatr Gastroenterol Nutr. 2025;80:617–622 Helicobacter pylori infection is associated with significant elevations to fecal calprotectin, systemic inflammatory markers

In this retrospective study from a high immigrant density community, patients aged 6–18 years old who had an fecal calprotectin (FC) level within 6 months prior to EGD and who were tested for HP infection were included in the study.

Key findings:

Of 129 patients, 37 (28.7%) tested positive for HP infection.
The mean FC level was significantly elevated in HP-positive patients (241.2) as compared with HP-negative patients (88.1) (p < 0.001)
HP-positive patients were also found to have small but notably higher elevations of CRP and ESR levels

My take: This study confirms what I have seen in my own practice. Patients with H pylori frequently have elevated calprotectin levels. Checking stool for H pylori may help avoid some colonoscopies. H pylori infection, however, can be present in patients with inflammatory bowel disease as well.

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Celiac Disease: Lower TTG-IgA Titers Associated with Isolated Duodenal Bulb Presentation

Posted on April 30, 2025 by gutsandgrowth

QY Wang et al. JPGN 2025; 80:678–685. Open Access! Low TTG-IgA associated with isolated bulb pathology in pediatric celiac disease: Implications in a no-biopsy approach era

Methods: There were 405 cases included in this retrospective study (mean age = 9.6 years). TTG-IgA values were considered negative if <4 U/mL, equivocal between 4 and 10 U/mL inclusively, and positive if >10 U/mL. At the authors’ institution, TTG‐IgA ≥10× ULN corresponds to ≥100 U/mL.

Key findings:

Bulb-restricted CD was present in 7.4% of cases
TTG-IgA was negative or equivocal in 60.0% of bulb-restricted CD, compared to 5.3% of distal duodenal CD (odds ratio [OR] = 26.6
No bulb-restricted CD cases attained TTG-IgA ≥10× ULN, compared to 48.5% of distal duodenal CD

My take: This study confirms and quantitates what most clinicians have experienced. Isolated duodenal bulb pathology is associated with lower celiac titer abnormalities.

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Gorgeous stained glass by Margaret Vetter at Piedmont Arts Festival

SNL: Flamin Hot Preparation H (Would Not Recommend)

Posted on April 29, 2025 by gutsandgrowth

SNL: Flammin Hot Commercial

Bowel Obstruction in Newborn

Posted on April 28, 2025 by gutsandgrowth

A Le-Nguyen. N Engl J Med 2025;392:1215. Meconium Ileus

An abdominal radiograph had shown dilated loops of small intestine (Panel A). Owing to concern for intestinal malrotation with midgut volvulus, an urgent laparotomy was performed. Considerable distention of the small bowel by thick meconium — rather than midgut volvulus — was identified. An enterotomy for evacuation of meconium was performed (Panel B). On postoperative genetic testing, the baby was found to be homozygous for a mutation in CFTR, the gene encoding cystic fibrosis transmembrane conductance regulator… The condition is associated with a very high risk of cystic fibrosis, so genetic testing is warranted in all cases. Uncomplicated cases are typically managed with serial enemas.

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Shingles Vaccine Linked to Lower Dementia Risk

Posted on April 27, 2025 by gutsandgrowth

L Carroll. NBC News, 4/2/25: Shingles vaccine may protect against dementia, new study suggests

An excerpt:

It’s been shown that reactivation of the chickenpox virus can lead to the accumulation of aberrant proteins associated with Alzheimer’s…

The new research, published Wednesday in Nature, analyzed data from more than 280,000 older adults in Wales and found that people who received the original shingles live virus vaccine were 20% less likely to develop dementia of any type than those who were not vaccinated...

The new study was possible because of an unusual public health policy in Wales that provided a “natural experiment” to explore the potential impact of the vaccine on dementia risk. With the rollout of the vaccine on Sept. 1, 2013, in Wales, shots were offered to people who were 79 on that date but not given to people who had turned 80. That allowed the German and Stanford University researchers to compare two groups of people with similar health characteristics who differed only by one week in age...

Bolstering the case for the shingles vaccine protecting against dementia were the findings from a study published in Nature Medicine in 2024 that analyzed medical records from more than 100,000 patients. That analysis suggested the newer shingles vaccine was associated with even better protection against dementia.

Actual study:Eyting, M., Xie, M., Michalik, F. et al. . Nature (2025). https://doi.org/10.1038/s41586-025-08800-x Open Access! A natural experiment on the effect of herpes zoster vaccination on dementia