Category Archives: Gastroenterology

Comprehensive ACG Clinical Guidelines for Ulcerative Coliits (2025)

Posted on by

D Rubin et al. The American Journal of Gastroenterology 120(6):p 1187-1224, June 2025. Open Access! ACG Clinical Guideline Update: Ulcerative Colitis in Adults

Today and tomorrow I am highlighting two adult clinical guidelines both of which are equivalent to up-to-date textbook chapters with specific recommendations; both are open access. In addition, the articles have accompanying author podcasts. Thanks to Ben Gold for these references.

Table 2 in the UC guideline makes 54 recommendations and Table 3 provides 57 key concepts.

Selected Management Recommendations:

  • Table 2, #4: We recommend treating patients with UC to achieve endoscopic improvement (Mayo score 0 or 1) to increase the likelihood of sustained steroid-free remission and to prevent hospitalization and surgery
  • Table 2, #5: We recommend the use of FC (fecal calprotectin) in UC to assess response to therapy, to evaluate suspected relapse, and during maintenance
  • Table 2, #33: When infliximab is used as induction therapy for patients with moderately to severely active UC, we recommend combination therapy with a thiopurine
  • Table 2, #43: Recommend continuing tofacitinib or upadacitinib as compared with no treatment for maintenance of remission in patients with prior moderately to severely active UC now in remission after induction with tofacitinib or upadacitinib. **The authors recommend continuing each biologic that achieved remission with induction therapy (#38-#43)
  • Table 2, #51: In patients with ASUC failing to adequately respond to intravenous corticosteroids (IVCS) by 3 days, we recommend medical rescue therapy with infliximab or cyclosporine (Strong recommendation, moderate quality of evidence).

Key concepts:

  • Table 3, #29: Patients who are primary nonresponders to an anti-TNF (defined as lack of therapeutic benefit after induction and despite sufficient serum drug concentrations) should be evaluated and considered for alternative mechanisms of disease control (e.g., in a different class of therapy) rather than cycling to another drug within the anti-TNF class.
  • Table 3, #31:  Subcutaneous infliximab and vedolizumab are considered equivalent to the standard intravenous maintenance dosing of these agents. The equivalence of the subcutaneous formulations for induction or as substitution for escalated doses of these therapies has not been robustly established.
  • Table 3, #41: Patients with UC should have available all medical options as recommended by their doctor and healthcare team. Third-party payers and requirements for step therapy should not come between the patient and their healthcare team in making decisions about treatment for UC.
  • Table 3, #48: All patients with ASUC should undergo a flexible sigmoidoscopy within 72 hours and preferably within 24 hours of admission. This should be used to assess endoscopic severity of inflammation and to obtain biopsies to evaluate for cytomegalovirus (CMV) colitis.
  • Table 3, #51: Nonsteroidal anti-inflammatory drugs (NSAIDs), narcotics, and medications with anticholinergic side effects should be avoided in ASUC.
  • Table 3, #57: In patients with ASUC initiating infliximab, dose intensification should be considered for those patients with low serum albumin (<2.5 g/dL).

My take: This article does an excellent job of summarizing current available evidence and good practice. Many of the recommendations may be helpful in garnering approval from third party payers.

Related blog posts:

Inability to Burp: How Effective is Botox?

Posted on by

Briefly noted: S Sanagapalli et al. The American Journal of Gastroenterology 120(9):p 2051-2058, September 2025. Prospective Controlled Study of Endoscopic Botulinum Toxin Injection for Retrograde Cricopharyngeus Dysfunction: The Inability to Belch Syndrome

This study explored a treatment with botulinum toxin (aka. Botox) for people who can’t belch due to a condition called retrograde cricopharyngeus dysfunction (R-CPD), which causes gas-related discomfort. Researchers used high-resolution manometry (HRM) with carbonated drink provocation to diagnose R-CPD. Then, they tested a treatment involving botulinum toxin injections into the cricopharyngeal muscle.

Out of 65 participants, 52 received the treatment, and 92% of those who received the treatment were able to belch after three months, significantly improving their symptoms and quality of life. In contrast, the control group, which included participants who deferred or declined treatment, saw no improvement. After 3 months, 43/51 (84%) of the treatment group reported being satisfied or very satisfied with therapeutic outcome.

Related blog posts:

Consensus Recommendations on Functional Bloating and Distention

Posted on by

C Melchior et al. United European Gastroenterology Journal, 2025; 00:1–39. Open Access! European Consensus on Functional Bloating and Abdominal Distension—An ESNM/UEG Recommendations for Clinical Management

A total of 21 experts (authors of article), recommended by ESNM, The European Association for Gastroenterology, Endoscopy and Nutrition (EAGEN) and The European Society for Primary Care Gastroenterology (ESPCG), from different countries agreed to participate as the International Working Group for the European Consensus on Bloating to vote on the Delphi statements.

This article regarding bloating/distension in adults is summarized in two tables. Table 1 has 75 statements. Table 2 is a summary –here are many of its recommendations:

Patients with functional bloating and abdominal distention should receive a lactose‐limiting diet trial based on their self‐reported symptoms or the presence of intolerance during a breath test after ingestion of a defined lactose load

  • A low FODMAP diet is effective in reducing functional bloating and abdominal distention
  • Rifaximin may be useful for the treatment of functional bloating and abdominal distention with efficacy
  • Among antispasmodic agents, pinaverium and otilonium bromide have been shown to be the most effective drugs for the treatment of functional bloating and abdominal distension
  • Lubiprostone, plecanatide and linaclotide are effective in improving constipation associated with functional bloating and abdominal distension
  • Linaclotide is the most effective secretagogue for functional bloating, although limited data is available for lubiprostone and plecanatide as well
  • Selective serotonin reuptake inhibitors (SSRI’s) are effective in reducing symptoms of functional bloating
  • Tricyclic antidepressants (TCA) such as amitriptyline are effective in reducing symptoms of functional bloating
  • In patients with discrete episodes of visible abdominal distension, biofeedback‐guided techniques to re‐educate abdominothoracic muscular activity are safe and effective for correction of abdominal distention and are associated with improvement in the subjective sensation of abdominal bloating
  • “Hypnotherapy improves symptoms of bloating in patients with IBS. However, its effect on functional bloating and abdominal distension was not explored and cannot be recommended”
  • Figure 1 provides an algorithm. For workup, it suggests checking the following in all patients: TSH, HgbA1c, CBC, CRP, TTG IgA, IgA, Glucose
  • In those with alarm features (eg. anemia, wt loss, suspicion of organic disease), more extensive evaluation is recommended

My take: One of my colleagues would often say that if there are a lot of treatments for a disease it usually indicates that none of them are very good.

Related blog posts:

Bouquet of Flowers, Claude Monet

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.

The Rise of Oral Obesity Therapies: Semaglutide and Orforglipron

Posted on by

SWharton et al. N Engl J Med 2025;393:1077-1087. Oral Semaglutide at a Dose of 25 mg in Adults with Overweight or Obesity

Methods: The participants were randomly assigned in a 2:1 ratio to receive oral semaglutide (25 mg) or placebo once daily, plus lifestyle interventions.

Key Findings:

In their discussion, the authors note that the reasons why “patients may prefer oral administration over the subcutaneous route are most often needle aversion and local skin reactions.7,8 In addition, unlike injectable agents, oral agents may not require a refrigerated chain of delivery and could widen the reach of obesity care in many regions of the world where a lack of refrigeration represents a barrier to access.”

In addition, the results were similar to the “STEP 1 (Semaglutide Treatment Effect in People with Obesity) trial of weekly subcutaneous semaglutide at a dose of 2.4 mg (12.4 percentage points more than that with placebo),16“

As with prior trials of semaglutide, “treatment was also associated with substantial reductions in cardiometabolic risk factors including BMI, waist circumference, and levels of glycated hemoglobin, fasting plasma glucose, fasting serum insulin, lipids (very-low-density lipoprotein and triglycerides), and C-reactive protein.”

My take: Effective oral therapy is a big advance for management of obesity. The entire field of pharmacology for obesity has seen remarkable advances in the past few years. For me, it is reminiscent of the proliferation of published studies for hepatitis C around 10 years ago.

Related article in same NEJM issue: J Rosenstock et al. N Engl J Med 2025;393:1065-1076. Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist, in Early Type 2 Diabetes

In the ACHIEVE-1 Trial: Key Findings (n=559 adults):

The associated editorial by DB Lowe (N Engl J Med 2025;393:1133-1134) notes that Orforglipron is a small molecule that manages to mimic the effects of glucagon-like peptide-1 (GLP-1) at the GLP-1 receptor. “The incretins, like many peptide hormones, are fairly small as proteins go — a few dozen amino acids long. But that makes them gigantic as compared with small-molecule drugs. Their molecular weights are at least 10 times as high as the 300 to 500 mass units that medicinal chemists have traditionally aimed for, and being peptides, they have generally undesirable properties as well. Many have short half-lives in the circulation, which can be a desirable feature for endogenous peptides but is nowhere near what is needed for the administration of a once-daily dose.”

Related blog posts:



AI for GI

Posted on by

This month’s Gastroenterology issue is devoted solely to the use/expected uses as well as risks of artificial intelligence (AI) for gastroenterology and hepatology.

DL Shung, M Iacucci. Gastroenterol 2025; 169: 391-392. Artificial Intelligence in Gastroenterology and Hepatology: Potential and Perils

An excerpt:

“AI is reshaping the landscape of gastroenterology and hepatology with the promise of better, faster, more objective, and standardized care of delivery. However, behind the algorithms lies a more insidious risk: the erosion of trust in human providers…Information risk …include both error commission (ie, when the models generate false statements, introduce nonsensical concepts, or fabricate sources) and error omission (ie, summaries that omit critical information)…

When AI becomes the center of care, patients may perceive their doctors as intermediaries…diminishing the therapeutic effect of the patient-physician relationship…This arrangement can dilute clinical training, increase physician burnout, and lead to medicolegal implications…Other risks include perpetuating bias from nonrepresentative training data and amplifying uncertainty of AI due to lack of real-world validation…

We hope that AI systems will allow us to spend more, not less, time with patients and empower us to provide personalized care by leveraging high-quality multimodal data.”

Most of the articles are behind a paywall in this issue. There are five that are open access articles:

My take: These articles provide a good deal of information about the applications and risks of AI. In my view, physicians will be needed more than ever to help interpret/manage the huge amount of information available.

Related blog posts:

Upadacitinib for Crohn’s Disease: U-ENDURE Study

Posted on by

R Panaccione et al. Clin Gastroenterol Hepatol 2025; (In press) Open Access! Upadacitinib Maintenance Therapy in Crohn’s Disease: Final Results From the Randomized Phase 3 U-ENDURE Study

Methods: Clinical responders to 12 weeks of upadacitinib 45 mg once daily (QD) induction were randomized (1:1:1) to receive upadacitinib 15 mg QD (n = 221), upadacitinib 30 mg QD (n = 229), or placebo (n = 223) as maintenance therapy for 52 weeks

**This study presents data from the entire cohort (n=673); a previous report from ENDURE-3 analyzed data on 502 patients (though findings were nearly identical). EV Loftus et al. N Engl J Med 2023; 388:1966-1980 (Related post: Landmark Study: Oral Biologic for Crohn’s –Upadacitinib)

Key findings:

  • At week 52, more upadacitinib-treated vs placebo patients achieved CDAI clinical remission (upadacitinib 15 mg, 36.2% and upadacitinib 30 mg, 51.5% vs placebo, 15.2%)
  • The rates of endoscopic response were 27.3% for upadacitinib 15 mg and 40.7% for upadacitinib 30 mg vs 7.2% for placebo
  • Herpes zoster infections occurred more frequently in the upadacitinib groups compared with placebo; all were nonserious, and most involved a single dermatome
  • In U-ENDURE, no dose-dependent risk for MACE, VTE, or malignancy (excluding NMSC) was observed during the 52-week maintenance period

My take: Upadacitinib is a effective in a good number of patients with with moderately to severely active Crohn’s disease who have been refractory to other advanced therapies.

Related blog posts:

What Caught My Eye in a Recent Anti-IL23 Commentary

Posted on by

This recent commentary on the all-subcutaneous induction and maintenance treatment with guselkumab, an anti-IL23 agent, reviewed the GRAVITI study. Related post: Guselkumab for Crohn’s Disease: Pivotal GRAVITI Study

However, what captured my attention was the last sentence: “The convenience of subcutaneous induction enhances patient friendliness, positioning guselkumab as a strong market contender. Could an oral anti–IL-23 formulation be the next game changer?14“

“Johnson & Johnson (NYSE: JNJ) today announced positive topline results from ANTHEM-UC, a Phase 2b study of icotrokinra (JNJ-2113), the first investigational targeted oral peptide that selectively blocks the IL-23 receptor, in adults with moderately to severely active ulcerative colitis (UC)…

In the ANTHEM-UC study (n=252), three doses of once daily icotrokinra were tested with all meeting the primary endpoint of clinical response at Week 12. A response rate of 63.5% for patients treated with the highest dose of icotrokinra was achieved at Week 12 versus 27% for placebo (p<0.001). Further, 30.2% of patients treated with the highest dose of icotrokinra demonstrated clinical remission at Week 12 versus 11.1% of patients who received placebo (p<0.01). Remission and response rates continued to improve through Week 28.

  • Clinical response is defined as decrease from baseline in the modified Mayo score by greater than or equal to (>=) 30 percent (%) and >=2 points, with either a >=1-point decrease from baseline in the rectal bleeding subscore or a rectal bleeding subscore of 0 or 1.
  • Clinical remission is defined as a Mayo stool frequency subscore of 0 or 1 and not increased from induction baseline, a Mayo rectal bleeding subscore of 0, and a Mayo endoscopy subscore of 0 or 1 with no friability present on the endoscopy.”

My take: It would be terrific for patients with inflammatory bowel disease (and other immune-mediated diseases) to have another excellent oral therapy. A prior study of plaque psoriasis indicated that an oral IL-23 medication is feasible (Related post: In Trials: An Oral IL-23 Antagonist Peptide).

Related joke (regarding “caught my eye” in the title of this post):

A man who lived in a block of apartments thought it was raining and put his head out the window to check.  As he did so a glass eye fell into his hand. He looked up to see where it came from in time to see a young woman looking down. “Is this yours?” he asked.

She said, “Yes, could you bring it up?” and the man agreed. On arrival she was profuse in her thanks and offered the man a drink. Shortly afterwards she said, “I’m about to have dinner.  There’s plenty; would you like to join me?” He readily accepted her offer and both enjoyed a lovely meal. As the evening was drawing to a close the lady said, “I’ve had a marvelous evening.  Would you like to stay the night?”  The man hesitated then said, “Do you act like this with every man you meet?”

“No,” she replied, “only those who catch my eye.”

The Manneporte by Claude Monet (at the Metropolitan Museum of Art)

Global Evidence of Gastric Cancer Prevention with Helicobacter pylori Eradication

Posted on by

Several recent articles have confirmed the benefits of H pylori eradication on reducing the risk of gastric cancer. This is in both Western and Eastern populations.

In this retrospective study from Nordic countries (Denmark, Sweden, Norway, Finland, and Iceland), researchers followed outcomes among ~700,000 people treated for H. pylori infection. The incidence of gastric adenocarcinoma was twice that of the general population in the first 5 years after treatment, likely reflecting H. pylori–related carcinogenesis that already was underway, but after 11 years, the incidence fell to that of the general population and remained there.

Discussion points:

  • The results of this study from 5 entire Western countries are in line with systematic reviews from Asian populations, indicating that H pylori eradication reduces the risk of gastric cancer
  • In addition, it has been proposed that eradication of H pylori might increase the risk of esophageal adenocarcinoma, but our recent study based on the NordHePEP found no such increase (Ref: Gastroenterology. 2024; 167:485-492.e3)

In this population-based study with more than 900,000 individuals, gastric cancer incidence and mortality rates were significantly lower in H pylori-treated individuals than in the general population.

In this meta-analysis of 11 randomized trials and 13 cohort studies researchers compared outcomes in treated and untreated H. pylori–positive adults. In both groups of studies, gastric cancer incidence was 40% lower in people who underwent H. pylori eradication. All but two of these studies were from eastern Asia.

 “In 2025, the IARC Working Group has issued a new report reaffirming H pylori eradication as a globally actionable and cost-effective intervention for the primary prevention of GC.18…Also, addressing the global public health challenge of antibiotic resistance remains essential, necessitating the development of susceptibility-guided or empirically optimized regimens tailored to local resistance patterns.

My take (borrowed from the commentary): “Despite the challenges, collectively, the emerging evidence from diverse populations reinforces the significant benefits of H pylori eradication in reducing GC incidence and mortality. These findings continuously support that H pylori eradication remains an effective preventive strategy across demographic settings, highlighting its relevance as a critical public health measure globally.”

Related blog posts:

IBS Impact: Survey Reveals Daily Life Struggles

Posted on by

AGA GastroNews, AGA IBS in America survey reveals IBS major burden despite advances in treatment (8/7/25):

Methods: The Harris Poll on behalf of AGA in 2024, among 2,013 U.S. adults age 18+ who have been diagnosed by a health care provider with IBS-C (1,005) or IBS-D (1,008). In addition, U.S. health care provider research was conducted online among 600 health care providers including gastroenterologists (n=200), primary care physicians (PCPs, n=200), gastroenterology nurse practitioners (NP)/physician assistants (PA) (n=100), and PCP NP/PAs (n=100)

Key findings:

  • IBS symptoms interfere with patients’ productivity at work/school for nearly 11 days per month on average
  • IBS symptoms disrupt personal activities eight days per month on average
  • 69% say their symptoms make them feel like they’re not “normal”
  • 77% avoid situations where bathroom access is limited.
  • 72% find it difficult to plan activities due to unpredictable symptoms.
  • 72% stay home more often because of their symptoms

My take: This sample of patients with IBS likely has more severe symptoms than a more general population of patients with IBS. Nevertheless, it highlights the impact of IBS symptoms on daily living.

Link: AGA IBS Toolkit

Related blog posts:

Westminster Abbey, London


“Are Marathons and Extreme Running Linked to Colon Cancer?”

Posted on by

NY Times 8/19/25: Are Marathons and Extreme Running Linked to Colon Cancer?

An excerpt:

A small, preliminary study found that marathoners were much more likely to have precancerous growths. Experts aren’t sure why…

Dr. Cannon, an oncologist with Inova Schar Cancer in Fairfax, Va., launched a study, recruiting 100 marathon and ultramarathon runners aged 35 to 50 to undergo a colonoscopy.

The results were staggering. Almost half the participants had polyps, and 15 percent had advanced adenomas likely to become cancerous. The rate of advanced adenomas was much higher than that seen among adults in their late 40s in the general population, which ranges from 4.5 percent to 6 percent, according to recent studies.

The research was presented at an American Society of Clinical Oncology conference but has not yet been published in a medical journal…

Dr. David Rubin, chief of gastroenterology and director of the Inflammatory Bowel Disease Center at the University of Chicago, said the study was important but limited. It lacked a control arm consisting of similar young adults who were not long-distance runners, he noted, and the family histories of colon cancer among the marathoners were not entirely known…

Runners often develop gastrointestinal symptoms that they dismiss as benign — so-called runner’s trots, for example. The symptoms can be caused by ischemic colitis, a condition that develops when blood flow to the colon is temporarily reduced as it is redirected to muscles in other parts of body (like a runner’s legs).

My take: While this is a small study, it indicates that extreme runners could have an increased risk of colonic polyps and cancer. If there are symptoms (especially rectal bleeding and weight loss), a low threshold for further evaluation is needed.

Related blog posts:

View of Statue of Liberty from Governor’s Island