Discordinate Recommendations for Celiac Screening with Down Syndrome

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VN Dargenio et al. J Pediatr Gastroenterol Nutr. 2026;83:304–313. A systematic review of celiac disease recommendations for children with Down syndrome

Background: “CD [celiac disease] prevalence in DS is higher than in the general population.10 The overlapping symptoms between CD and DS, such as growth failure, fatigue, GI disturbances, and, less frequently, neurological and behavioral problems, pose significant diagnostic challenges, as these are often attributed to underlying DS comorbidities, leading to delays in recognizing CD.4, 11 

Guidelines:

The authors note wide variation in the prevalence of CD in DS in various studies. “A meta-analysis of 31 studies including 4383 individuals found a pooled prevalence of biopsy-confirmed CD of 5.8% (95% CI 4.7%–7.2%), with slightly higher rates in children (6.6%) compared to mixed-age samples (5.1%)31…these findings align with the 5%–13% prevalence range documented in earlier European studies2“

The authors recommend the following strategy:

“Given the high prevalence of asymptomatic and atypical presentations, reliance on symptoms alone is insufficient. A pragmatic strategy should initiate with universal serological screening for all children with DS after gluten introduction (12–24 months of age), followed by periodic re-screening every 2–3 years, using tTG-IgA with total IgA assessment, supplemented by IgG-based assays in the context of the high rate of selective IgA deficiency in DS.”

My take: There are wide discrepancies in the recommendations for screening for celiac disease in asymptomatic individuals with Down syndrome.

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Evaluation of the Rumination Severity Index (RumSI) and Usefulness for Clinical Practice

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JS Khoo, D Yang et al. J Pediatr Gastroenterol Nutr. 2026;83:251–257. The rumination severity index: Development and evaluation of a scoring tool for rumination syndrome

Methods: 66 children with rumination syndrome (RS) completed the 7-item RumSI and PedsQL questionnaires between 2018 and 2023.

RumSI Scoring: Skipped meals, weight loss due to vomiting, and use of a feeding tube or parenteral nutrition were each dichotomized, with absence of the symptom assigned a score of zero for each item and presence of the symptom assigned a score of 1.5σ = 4, where σ is the standard deviation of the combined vomiting/re-swallowing score. Both skipped days of school and social activities in the past 60 days were grouped into categories of 0, 1–4, 5–9, 10–19, 20–39, and 40–60 and assigned integer values of zero to five. The overall RumSI score was calculated by summing the six individual components (vomiting/re-swallowing, skipped meals, weight loss, use of feeding tube or parenteral nutrition, skipped days of school, and skipped days of sports/social activities).

Key Findings:

  • RumSI scores ranged from 0 to 26.5 (mean 10.6 ± 7.2) out of a total possible 28, with higher scores indicating worse rumination symptoms
  • RumSI and PedsQL scores were significantly negatively correlated (r = −0.45, p < 0.001), with every 1-point increase in RumSI score associated with a 1.3-point decrease in PedsQL total score
  • Higher RumSI scores were associated with co-morbid conditions including depression, functional dyspepsia, functional nausea/vomiting, gastroparesis, and postural orthostatic tachycardia syndrome

My take: Currently, the RumSI score would be cumbersome in clinical practice (in the absence of an embedded calculator). However, the questions on the RumSI are very useful and I already made a smartphrase to help capture this information on patients with suspected rumination. Also, the RumSI should be useful for research studies by offering a common scoring system to define and track disease burden.

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Misleading Autoimmune Markers in Wilson Disease Diagnosis

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AS Patel et al. J Pediatr Gastroenterol Nutr. 2026;83:241–246. False positive autoimmune markers and elevated immunoglobulin G in genetically confirmed Wilson disease

Key findings:

  • Elevated IgG (>1.1× upper limit of normal) was observed in 82.3% of WD patients, while 31.5% tested positive for at least one autoantibody
  • 20.2% of WD patients met the simplified diagnostic criteria for AIH
  • Liver histology findings were available in 25 WD patients. Compared to AIH, WD patients were less likely to have interface hepatitis (40% vs. 89%; p < 0.001) and plasma cell infiltrates (32% vs. 72.6%; p = 0.009), while having a higher presence of glycogenated nuclei (24% vs. 6.2%; p = 0.009), ballooning degeneration (56% vs. 33%; p = 0.024), and steatosis (52% vs. 9.8%; p < 0.001). Copper quantification studies were not done

Discussion Points:

  • “Reports of co-existence of WD and AIH in children further complicate the diagnosis.16, 17“
  • “The presence of elevated IgG and autoantibodies, often interpreted as supportive diagnosis of AIH, may be misleading in WD.”

As an aside, I disagree with the authors introduction that “Wilson disease (WD) and autoimmune hepatitis (AIH) are the two most common treatable causes of chronic liver disease (CLD) in children.1, 2” Clearly, steatotic liver disease is the most common treatable chronic liver disease in children; in addition, both hepatitis B and hepatitis C are more common as well.

My take: A low threshold for testing of WD is needed in patients diagnosed with autoimmune hepatitis; this could include genetic testing and/or coppor quantification in liver biopsies..

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Helicobacter pylori Treatment 2026

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T Rokkas, DY Graham. Gastroenterol 2026; 171: 271-284. The Unfinished Agenda in Helicobacter pylori Treatment: Resistance, Microbiome Effects, and Future Directions

This was a narrative review aimed at synthesizing contemporary evidence.

Background: Globally, approximately half of the population is infected. Prevalence surpasses 70% in many low- and middle-income countries (LMICs) where crowded living conditions, poor sanitation, and limited access to clean water enhance transmission. 

Key points:

  • Global resistance to clarithromycin, metronidazole, and fluoroquinolones significantly undermines the performance of traditionally effective antimicrobial therapies. The corner stone of successful antimicrobial therapy is susceptibility-guided therapy but remains of limited use with H pylori because of lack of infrastructure.
  • Clarithromycin should no longer be prescribed as an empiric therapy (ie, it should be restricted to susceptibly based therapy)…Despite the poor cure rates with clarithromycin achieved with vonoprazan in the United States, the American College of Gastroenterology H pylori guideline still recommended vonoprazan triple therapy.17 (With clarithromycin-susceptible infections, vonoprazan is not more effective than PPIs.) The discordance between guideline recommendations and clinical effectiveness contributes to treatment failures.
  • Bismuth quadruple therapy (BQT), which combines metronidazole with tetracycline and bismuth, can partially overcome moderate metronidazole resistance through antimicrobial synergy and higher effective dosing.
  • Next-generation sequencing (NGS) is now available at a fraction of the cost of an endoscopy in the United States using stools, fresh, frozen, or paraffin-embedded gastric biopsies37 (American Molecular). Economic analyses indicate that susceptibility-guided therapy is cost-effective.
  • When BQT fails or is unavailable, several alternative regimens can be considered.4–6 Rifabutin-based triple therapy can achieve eradication rates of 70% to 90% even in heavily pretreated patients.40
  • When designing rescue therapy, antibiotics previously associated with failure should not be reused unless susceptibility has been clearly established.
  • Optimizing H pylori treatment requires evidence-based regimen selection, precision-guided strategies, antimicrobial stewardship, and equitable access to essential medications

My take: This is a helpful review of H pylori issues and management.

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Should the Gluten Threshold Dose in Celiac Disease Change Based on Immune Activation?

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Background: Interleukin 2 (IL2) rises acutely after gluten ingestion, allowing the definition of threshold doses that trigger immune activation.

Methods: This was a randomized double-blind, placebo-controlled adaptive dose–response trial in adults with biopsy-proven celiac disease on a gluten-free diet for >2 years. Participants (n = 51; median age, 52 years; 69% were female) underwent 3 oral gluten (1–1000 mg) or placebo challenges at 4-week intervals. Eliciting dose (EDp, ie, the dose at which p% of people respond) was estimated by interval-censored survival analysis.

Key findings:

  • Gluten induced dose-dependent IL2 elevations, with ≥2-fold increases in 83% at 1000 mg, 83% at 610 mg, 36% at 90 mg, 17% at 13 mg, 27% at 8 mg, and 17% at 3 mg; none responded to 5 mg, 2 mg, 1 mg, or placebo.  
  • Estimated ED50 was 111 mg, ED10 was 2.4 mg, ED05 was 0.8 mg, and ED01 was 0.1 mg

From the editorial:

“To date, the few investigators who addressed this question defined tolerance in relation to quantifiable histologic damage (intestinal morphometry)…Bearing in mind that the typical Western diet contains 10–15 g of gluten per day, these studies found that the protracted, daily ingestion of 1000, 200, or 50 mg of gluten elicits significant damage at the mucosal level.2,3 A daily dose of 10 mg was also associated with minimal architectural changes in some patients…

In 2007, the Food and Agricultural Organization/World Health Organization Codex Alimentarius Commission4 applied these findings to establish that commercially available gluten-free food must not contain more than 20 mg/kg gluten (20 part per million [ppm]), as this would ensure that daily gluten intake does not exceed 10 mg…Not a single case of proven intolerance to 20 ppm gluten-free food has been described…in some 20-ppm countries, most labeled gluten-free products already contain much less than 20 ppm of gluten, usually <10 ppm5…

The authors concluded that the daily gluten threshold should be decreased because acute IL2 release occurred at 3 mg, which is less than is allowed by current food-labeling rules for gluten-free products…

Because symptoms did not correlate with the result of the IL2 test for gluten doses <1 g, further prolonged microchallenge studies remain the only reliable strategy to investigate the correlation between the IL2 test and the gold standard of CeD activity—histologic damage of the small intestinal mucosa.10,11“

My take: This study is intriguing that there is evidence of immune activation at lower gluten exposures; however, it does not prove that changing the gluten threshold is beneficial.

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Breaking the Silence: A Doctor’s Struggle with Mental Health

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T Khan et al. NEJM 2026; 395: 529-531. Doctor’s Dirty Little Secret — The Cost of Silence

An excerpt:

No one would suspect that for the past month I’d been plotting my death. Death felt like the only way to let go of the fear and exhaustion that was swallowing me whole…

“You know we don’t lock people up just for having suicidal thoughts anymore, right?” The on-call emergency psychiatrist’s tone, though comforting, was edged with frustration…

“Most of us have had thoughts of suicide at some time in our careers,” she said plainly. “It’s an occupational hazard — like a needlestick or missing your kid’s recital.”

With those matter-of-fact words, she named the doctor’s dirty little secret: we are human. But we believe this admission could cost us everything. That curbside consult saved my life. For the first time in a long while, I didn’t feel alone.

I’d been an emergency doctor for nearly half my life, running on a steady drip of cortisol. By my 40s, my body struggled to keep pace with the demands of the job…

I was responsible for everyone and everything all at once — crisis, illness, intoxication, and circumstance colliding, each person having been carried to me by whatever fear or fate had gripped them. I absorbed the frequent interruptions along with the urgency and blame, until the weight of it all settled as a constant heaviness in my chest…

I was deep in burnout.

And I am not alone. In the United States, female physicians die by suicide at more than 2.27 times the rate of women in the general population, and male physicians at 1.41 times the rate of men in general.1 These statistics are not abstract. They reflect the real suffering of physicians, who are also children, spouses, parents, siblings, and friends, and they reflect a story I never expected would one day become my own. The data challenge the enduring myth that doctors are somehow superhuman…

Despite copious literature on burnout, effective solutions remain scarce…many of us find deep meaning in our work, which fuels perseverance even in the face of adversity…

It took crashing into a wall for me to understand the delicate dance between grit and resilience. Grit is the pedal that drives us forward; resilience is the wheel that helps us change course. Resilience guided me to seek help — which was surprisingly difficult to find…

I kept my license, my family, and my life — for now. But many physicians aren’t as fortunate. Shame, stigma, and institutional failures may keep them silent, but silence is not strength. And asking for help is not a betrayal of the profession.

Related article: A Albert. Gastro & Endo News July 2026. Listen to Your Youngers: Why Gen Z Doctors Refuse to Die for RVUs Open Access! “I think we do better by our patients when we do better for ourselves…The younger generation isn’t “killing” medicine. They’re trying to survive it. They’re realizing that an exhausted, dehydrated doctor who hasn’t seen sunlight in three days isn’t “dedicated”—they’re a liability.”

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Practice-Changing Study on Minor Papillotomy for Treatment of Pancreas Divisum

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GA Cote et al. JAMA 2026; 335;(8):682-692. doi:10.1001/jama.2025.23988. Open Access! Minor Papillotomy for Treatment of Idiopathic Acute Pancreatitis With Pancreas Divisum: A Randomized Clinical Trial

Background:  When pancreas divisum is identified by cross-sectional imaging, many clinicians proceed to ERCP with minor papillotomy because of its suggested benefit in reducing future episodes of pancreatitis. This practice has been disputed because pancreas divisum is present in 7% to 10% of asymptomatic individuals…the primary aim of the Sphincterotomy for Acute Recurrent Pancreatitis (SHARP) trial was to determine if ERCP with minor papillotomy reduces the risk of acute pancreatitis in patients with pancreas divisum and otherwise unexplained acute recurrent pancreatitis.

Normal Pancreatic Anatomy:

Methods: This multicenter, sham-controlled, double-blind randomized clinical trial enrolled adults (n=148) with 2 or more episodes of acute pancreatitis and pancreas divisum; participants were followed up for a median of 34 months. Adults with other etiologies for acute pancreatitis or concomitant chronic calcific pancreatitis were excluded.

Key findings:

  • ERCP with minor papillotomy did not significantly reduce the rate of acute pancreatitis during follow-up (34.7% vs 43.8% for sham ERCP; adjusted hazard ratio, 0.83).
  • The adverse event of acute pancreatitis within 30 days of randomization occurred more frequently in the ERCP with minor papillotomy group (14.7%) vs the sham ERCP group (8.2%) 
  • There was no between-group difference in acute pancreatitis episode frequency and development of chronic calcific pancreatitis, diabetes, or exocrine pancreatic dysfunction.

Discussion: “The current trial showed that patients who underwent ERCP with minor papillotomy did not have a lower risk of developing another episode compared with those managed conservatively (sham ERCP). The added risk of post-ERCP pancreatitis (occurred in 13.3% of ERCP with minor papillotomy group vs 0% with sham ERCP) furthers the argument to avoid minor papillotomy for pancreas divisum alone and controverts years of teaching that had been grounded in data from cohort studies suggesting a benefit.”

My take (borrowed from authors): Among patients with unexplained acute recurrent pancreatitis and pancreas divisum, ERCP with minor papillotomy does not reduce the risk of another episode of acute pancreatitis or related sequelae.

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A Natural Experiment: Sugar Rationing and Metabolic Dysfunction-Associated Steatotic Liver Disease

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J Zheng et al. Clinical Gastroenterology Hepatology 2026; 24: 2168-2180. Open Access! Sugar Rationing in the First 1000 Days After Conception and Long-Term Risk of Metabolic Dysfunction-Associated Steatotic Liver Disease and Major Adverse Liver Outcomes: A Natural Experiment Study

A previous blog post (The Hidden Dangers of Early Sugar Exposure) reviewed the beneficial effects of sugar rationing in Britain around WWII. There were lower rates of type 2 diabetes and hypertension.

Today’s article, reviews the effects of sugar rationing on liver outcomes.

Methods:

Key findings:

  • Among 63,698 participants, early-life sugar rationing was associated with a 30% reduced risk of MASLD (hazard ratio, 0.70), 17% lower risk of metabolic dysfunction-associated steatotic liver disease with alcohol consumption, 35% for major adverse liver outcomes, and 32% for cirrhosis. 
  • The protective effect increased with longer exposure.

My take: Reducing sugar, including in the prenatal period, reduces the risk of adverse liver outcomes in addition to type 2 diabetes and hypertension.

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From AGA Today in Medicine on 8/19/26 – Ongoing Cyclospora Outbreak:

Negative Study: Nortriptyline for Functional Dyspepsia

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Yesterday’s post showed that peppermint oil/sweets were not superior to placebo for management of pediatric IBS. Today’s study, likewise, shows that nortriptyline was not superior to placebo for functional dyspepsia, another DGBI. At the same time, the trials also showed fairly high response rates along with low adverse effect rate.

Methods: This was a multicenter, RCT of patients with FD (functional dyspepsia) in primary, secondary, and tertiary care. Sixty-nine participants were randomly assigned to nortriptyline (weeks 1–2: 10 mg; weeks 3–4: 25 mg; weeks 5–12: 50 mg) vs placebo for a 12-week treatment. The primary outcome was clinical response based on a decrease in FD symptoms of at least 30% compared with baseline, in 50% of the last 10 weeks of the treatment period.

Key finding:

  • The primary outcome showed no significant difference in response for nortriptyline compared with placebo (45% vs 58%; odds ratio [OR], 0.574)
  • There was no significant difference in adverse events between the nortriptyline and placebo group
  • Nortriptyline plasma levels were significantly higher in responders compared with non-responders (13.0 μg/L vs. vs 9.0 μg/L; P = .003)
  • The belief to have received nortriptyline showed a higher response rate than the belief to have received placebo (77% vs 36%; OR, 11.439; P = .004)

The accompanying editorial makes several important points:

  • “Placebo response is intrinsic to all DGBI trials. Across pediatric and adult populations, placebo response rates of 30% to 60% are common.3–5 Symptom fluctuation, regression to the mean, expectation bias, and cognitive–affective modulation of visceral perception all contribute. In children, parental expectations and heightened suggestibility may further amplify contextual effects. Nevertheless, they also highlight that placebo effects are an integral part of the therapeutic response seen in DGBI trials and clinical practice.”
  • “Expectancy effects deserve deliberate consideration in both trial design and clinical care. The nortriptyline trial elegantly demonstrated that participants’ belief or expectation about treatment allocation was more strongly associated with response than the medication itself…In clinical practice, clear explanations, symptom validation, confident framing of the treatment rationale, and a strong clinician–patient alliance can ethically harness expectancy and placebo effects to enhance response.6“
  • “Neither study suggests that pharmacologic therapy has no role in management. The association between higher nortriptyline plasma levels and response leaves open the possibility that a subset of patients derive biological benefit. Likewise, peppermint oil was safe and well-tolerated. However, these trials caution against overinterpreting modest signals from small or uncontrolled studies and emphasize the importance of adequately powered, methodologically rigorous trials in conditions characterized by high placebo response.”

My take: Rigorous pharmacologic studies show that medications, to date, recommended for patients with DGBIs have difficulty outperforming placebo; yet, there is a high response in patients with DGBIs. In this setting, the use of medications with a low incidence of adverse effects and plausible beneficial effects continue to have a role in improving symptom control.

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