Category Archives: Gastroenterology

INNOCENT Study: Psychological Impact for Gastroenterologist Associated with Procedural Complications

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Holzwanger, Erik A. et al. Gastroenterology 2025. Psychosocial Impact of Endoscopic Procedural Complications on Gastroenterologists: The Second Victims

Background: “Serious adverse events (SAEs) are unavoidable occurrences for those performing complex endoscopic interventions. These affect not only the patient (the first victim), but also possibly the proceduralist (the second victim). Second victim syndrome (SVS) was first described by Dr. Wu detailing the negative psychological effects of adverse patient events on physicians (Ref: Wu AW. Medical error: the second victim. BMJ. 2000;320(7237):726-727).”

Methods: Survey responses form “X” platform (n=195) were collected in 2023. Only
responses from advanced endoscopists (defined as those who perform either endoscopic
ultrasound or endoscopic retrograde cholangiopancreatography annually) and advanced
endoscopy fellows were included.

Key findings:

  • Higher procedural volume (>1000/year) was associated with feelings of greater emotional preparedness for SAEs
  • Speaking with colleagues (53%), exercise (33%), discussions at conferences (17%) and meditation (8%) were rated as used and very or extremely helpful

Discussion Points: “Peer support programs have proven to be well received and highly utilized. Additionally, surgeons criticize the often-punitive handling of SAEs, and note that the tone and culture in the review process following an SAE dictates reduction or exacerbation of SVS.”

My take: When I have had a complication in a patient, speaking with colleagues has provided a lot of support. One book I have recommended to others is the following: Complications: A Surgeon’s Notes on an Imperfect Science by Atul Gawande.

Related article (2022): “We Suffer in Silence” The Challenge of Surgeons as Second Victims

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Sterile Water is Unnecessary for Endoscopy

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From AGA Today (8/5/25): “Sterile Water is Unnecessary for Endoscopy”

GI and Hepatology News (8/4, Pass) reports a review suggests that “endoscopists can safely forgo sterile water in favor of tap, reducing both environmental and financial costs.” Researchers found that only two studies since 1975 “directly compared sterile and tap water use in endoscopy,” and “neither showed an increased risk of infection from tap water. In fact, some cultures from allegedly sterile water bottles grew pathogenic bacteria, while no patient complications were reported in either study.” Current guidelines “recommend sterile water for procedures involving mucosal penetration but acknowledge low-quality supporting evidence.” However, they pointed out that “these recommendations are based on outdated studies, some unrelated to GI endoscopy.” Furthermore, the “review estimates that the production and transportation of sterile water bottles contributes over 6,000 metric tons of emissions per year from US endoscopy units alone.” The review was published in Gastro Hep Advances.

Referenced article: D Agrawal, et al. Gastro Hep Advances, Volume 4, Issue 5, 100625. Ripple Effect: Safety, Cost, and Environmental Concerns of Using Sterile Water in Endoscopy

Environmental Costs:

“With a conservative estimate of using half of a 1-L sterile bottle for irrigation per endoscopy, 22 million yearly endoscopies in the US could result in an additional 6000 tons of eCO2.”

Economic Costs:

“A 1-L bottle of sterile water costs $3–$10. For an endoscopy unit performing 30 procedures daily and a conservative estimate of half a water bottle per case, the average monthly direct costs could be $1000–$3000”

Discussion:

“There is no direct supporting evidence for using sterile water during endoscopy…a Cochrane review show no difference in infection risk when using tap or sterile water to irrigate wounds…Similarly, there is no benefit in using sterile water for enteral feeds in immunosuppressed patients, and tap water enemas are routinely acceptable for colon cleansing before sigmoidoscopies in all patients, irrespective of immune status.

My take: Plastic water bottles in endoscopy centers contribute to health-care waste, climate change and increased costs.

Related blog post: Environmental Impact of Endoscopy

Sandy Springs, GA

Guselkumab for Crohn’s Disease: GALAXI-2 and GALAXI-3: 48-Week Results

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R Panaccione et al. The Lancet. Published online July 17, 2025 https://doi.org/10.1016/S0140-6736(25)00681-6. Efficacy and safety of intravenous induction and subcutaneous maintenance therapy with guselkumab for patients with Crohn’s disease (GALAXI-2 and GALAXI-3): 48-week results from two phase 3, randomised, placebo and active comparator-controlled, double-blind, triple-dummy trials

Methods: “GALAXI-2 and GALAXI-3 were identically designed, phase 3, randomised, double-blind, triple-dummy, treat-through trials with active and placebo comparators…1048 participants were randomly assigned, treated, and followed up until week 48, of whom 1021 participants were included in the primary analysis population: 508 (49·8%) in GALAXI-2 and 513 (50·2%) in GALAXI-3.” The studies enrolled adult patients with moderately to severely active Crohn’s disease.

Key findings:

Discussion points:

  • “Guselkumab treatment in participants with moderately to severely active Crohn’s disease was also evaluated in the GRAVITI study, which had a fully subcutaneous induction and maintenance treatment regimen. Clinical and endoscopic outcomes reported with subcutaneous guselkumab induction in the GRAVITI study were similar to those in the phase 3 GALAXI studies following intravenous guselkumab induction.”
  • “The incidence of adverse events with guselkumab during induction was low and similar to placebo.”

My take (borrowed from authors): In GALAXI-2 and GALAXI-3, both guselkumab dose regimens (each including intravenous induction and subcutaneous maintenance) were superior to placebo for short-term (week 12) and long-term (week 48) endpoints and both guselkumab dose regimens were also superior to ustekinumab

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Medications and the Risk of Microscopic Colitis

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H Khalili et al. Annals of Internal Medicine 2025; https://doi.org/10.7326/ANNALS-25-0026. Medications and Risk for Microscopic Colitis: A Nationwide Study of Older Adults in Sweden

Methods: The authors used Total Population Register, which includes information on the age and sex of all residents in Sweden. Then the cohort of older adults in Sweden was linked to the ESPRESSO study), which contains data on GI-related biopsies from all 28 pathology departments in Sweden from January 1965 until April 2017.

Key findings:

  • Estimated 12-month risk differences were close to null under angiotensin-converting enzyme versus calcium-channel blocker (CCB) initiation, angiotensin-receptor blocker versus CCB initiation, nonsteroidal anti-inflammatory drug initiation versus noninitiation, proton-pump inhibitor initiation versus noninitiation, and statin initiation versus noninitiation. 
  • There was a slight increase risk of microscopic colitis in patients receiving SSRIs compared to mirtazapine. The estimated 12-month risk difference was 0.04% (95% CI, 0.03% to 0.05%) for selective serotonin receptor inhibitors (SSRIs) versus mirtazapine.
  • Several medications were also associated with increased risk for receiving a colonoscopy with a normal colorectal mucosa biopsy result.

My take: Microscopic colitis is a very infrequent problem in the pediatric population. With the exception of SSRIs, this study in older adults did not find a significant relationship between purported “trigger” medications and the development of microscopic colitis. In addition, the low persistent associations with SSRI initiation may be due to surveillance bias.

Impact of Mediterranean Diet on Constipation

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Y Wang et al. Gastroenterol 2025; (Epub). Dietary Patterns and Incident Chronic Constipation in Three Prospective Cohorts of Middle- and Older-aged Adults

Methods: In three large cohorts, the Nurses’ Health Study (NHS), NHSII, and the Health Professional Follow-up Study (HPFS) (combined >95,000 participants), the authors identified chronic constipation based on repeatedly-measured self-reported constipation symptoms for ≥12 weeks in the past year.

Key Findings:

  • The top quintiles of alternate Mediterranean diet (aMED) and plant-based dietary index (PDI) were associated with 16% (9-22%) and 20% (14-27%) reduced risk for constipation. Vegetable and nut intake, which are enriched in aMED and PDI, were associated with decreased constipation risks.
  • A Western diet in the top quintile was associated with a 22% (11-33%) increased risk for constipation

My take: The results from this study are not surprising, but nice to see more data on the effects of diet on constipation. While this data focused on adults, it is clear that dietary patterns have a big role in the frequency of constipation in children too.

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Once-Weekly Mazdutide: Effective for Overweight and Obesity (GLORY-1 Study)

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L Ji et al. NEJM 2025; 392: 2215-2225. Once-Weekly Mazdutide in Chinese Adults with Obesity or Overweight

This study from China enrolled young participants (mean age 34 yrs) and lower BMI (mean 31.1) than in similar studies of other GLP1 RAs and GLP 1 RA/GIP dual agonists. However, there was a high prevalence of dyslipidemia (62.3%), MAFLD (48.9%), hyperuricemia (40.2%), and hypertension (22.8%).

Key findings:

  • At week 48, the mean percentage change in body weight from baseline was –11.00% in the 4-mg mazdutide group, –14.01% in the 6-mg mazdutide group, and 0.30% in the placebo group

My take: Mazdutide resulted in significant weight loss along with improvements in cardiometabolic measures. This study shows beneficial effects in a younger cohort with significant cardiometabolic disease. Improvements in younger populations is likely to result in more substantial effects on outcomes than improvement in older cohorts.

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Pilot Study: Mediterranean Diet vs Low FODMAP for Irritable Bowel Syndrome

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S Singh et al. Neurogastroenterology and Motility 2025; https://doi.org/10.1111/nmo.70060. Open Access! Efficacy of Mediterranean Diet vs. Low-FODMAP Diet in Patients With Nonconstipated Irritable Bowel Syndrome: A Pilot Randomized Controlled Trial

Methods: Patients were randomized controlled trial (RCT), adult patients with diarrhea-predominant IBS (IBS-D) or mixed bowel pattern (IBS-M) were randomized to Mediterranean diet (MD) versus a diet low in fermentable oligo-, di-, monosaccharides, and polyols (LFD) for 4 weeks. 10 patients completed the study in each group. The primary endpoint was the proportion of patients with ≥ 30% decrease in abdominal pain intensity (API) for ≥ 2/4 weeks. Daily variables included abdominal pain intensity (API) and bloating, while IBS symptom severity score (IBS-SSS) and IBS adequate relief (IBS-AR) were scored weekly

Key findings:

  • 73% percent of the MD group met the primary endpoint compared to 81.8% of the LFD group (p = 1.0)
  • Although not statistically significant, a numerically higher proportion of the LFD group reported adequate relief and met the responder endpoint for IBS-SSS (50-point reduction) compared to the MD group (54.6% vs. 27.3% for IBS-AR and 81.8% vs. 45.5% for IBS-SSS, p = 0.39 and 0.18, respectively)
  • The LFD group also had a significantly greater reduction in IBS-SSS score over the 4-week treatment period compared to the MD group (−105.5 vs. −60, p = 0.02)

My take (borrowed from authors): A Mediterannean diet “improves abdominal symptoms in the majority of patients with IBS-D and IBS-M. Larger, adequately powered, real-world studies comparing the efficacy of a MD with LFD and NICE diet are needed to validate these preliminary findings and to help patients and providers to know if a MD should be added to the list of effective, evidence-based diet interventions for patients with IBS.”

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Guselkumab for Crohn’s Disease: Pivotal GRAVITI Study

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A Hart et al. Gastroenterol 2025 (ePUB Ahead of Print) Open Access! Efficacy and Safety of Guselkumab Subcutaneous Induction and Maintenance in Participants With Moderately to Severely Active Crohn’s Disease: Results From the Phase 3 GRAVITI Study

Background: “Guselkumab is a selective dual-acting IL-23p19 subunit inhibitor that potently neutralizes IL-23 by binding to the p19 subunit and to CD64, a receptor on cells that produce IL-23…In the double-blind Phase 2 GALAXI 1 study and the 2 identically designed double-blind Phase 3 GALAXI 2 and GALAXI 3 studies, guselkumab intravenous (IV) induction (200 mg at weeks 0, 4, and 8) followed by subcutaneous (SC) maintenance (200 mg every 4 weeks or 100 mg every 8 weeks) demonstrated efficacy compared with placebo… In addition, guselkumab demonstrated superiority to ustekinumab for multiple endoscopic-based endpoints at week 48 in pooled data from GALAXI 2 and GALAXI 3… The GRAVITI study…evaluated the efficacy and safety of guselkumab SC induction followed by SC maintenance in participants with moderately to severely active Crohn’s disease.

Methods: This was a Phase 3 double-blind, placebo-controlled, treat-through GRAVITI study randomized 347 participants 1:1:1 to guselkumab 400 mg SC every 4 weeks→100 mg SC every 8 weeks (n = 115), guselkumab 400 mg SC every 4 weeks→200 mg SC every 4 weeks (n = 115), or placebo (n = 117).  Placebo participants meeting rescue criteria received guselkumab from week 16 onward. 

Key Findings:

  •  At week 12, significantly greater proportions of participants receiving guselkumab 400 mg achieved clinical remission vs placebo (56.1% vs 21.4%; P < .001), and endoscopic response vs placebo (41.3% vs 21.4%; P < .001)
  • At week 48, significantly greater proportions of participants in both guselkumab groups (100 mg SC every 8 weeks: 60.0%; 200 mg SC every 4 weeks: 66.1%) achieved clinical remission vs placebo (17.1%; P < .001 each) and endoscopic response (44.3%; 51.3%; vs placebo 6.8%; P < .001 each)
  • Immunogenicity: “Antibodies to guselkumab were detected in 24 (8.8%) of the 274 guselkumab-treated participants through week 48. Only 3 of 274 participants (1.1% of the total population) were positive for neutralizing antibodies. Through week 48, no impact of antibodies to guselkumab on serum guselkumab concentrations, efficacy, or injection-site reactions was observed”
At week 12: Compared to placebo, patients receiving Guselkumab had improved clinical remission and endoscopic response. Being naive to previous biologics was associated with a higher endoscopic response but with a lower clinical remission rate.
At week 48: Being naive to previous biologics was associated with a higher clinical remission
At week 48: Being naive to previous biologics was associated with a higher endoscopic remission

Discussion: “The results presented here from GRAVITI were consistent with those reported in the double-blind, treat-through GALAXI trials in which guselkumab induction was administered IV in participants with moderately to severely active Crohn’s disease. For example, 41.3% of participants in the GRAVITI study achieved endoscopic response 12 weeks … whereas 36.9% of participants in the pooled GALAXI studies achieved endoscopic response 12 weeks after guselkumab… IV induction (placebo: 12.2%).”

My take: This study shows that Guselkumab with a SC induction is safe and effective in participants with moderately to severely active Crohn’s disease. IV induction does not appear to be needed. Though IL-23 agents have been important advances, there are still a large number of patients without a good response.

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Yoda, the Hulk and Kermit Look Good in Green. What About the Endoscopy Suite?

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T Walradt, D Svarca. Gastroenterology 2025; 168: 1046-1048. Shining a New Light on
Gastrointestinal Endoscopy: Evaluating the Effect of Green Light vs Dim Light on Performance in the Endoscopy Suite

Background: “Unlike diagnostic radiology, GI endoscopy requires the concerted efforts of a proceduralist, anesthesiologist, nurse, and technician. Moreover, several of these individuals are often performing tasks that do not involve looking at a monitor. The advent of laparoscopic surgery presented surgeons with similar lighting challenges. In response to this problem, some operating rooms have been equipped with green lights to achieve high contrast and low glare on monitors while still allowing for the safe and efficient practice of other tasks in the operating room. The choice of green light is based on the fact that the human eye is most sensitive to light with a wavelength around 555 nm, in the green portion of the visible spectrum. This wavelength provides optimal contrast and sharpness under low-light conditions.”

Methods: The authors “conducted a single-center cross-over study comparing image
classification on video monitors and the performance of multiple nonmonitored based physical tasks in the endoscopy suite using green light and dim light.”

Key findings:

  • Performance of physical tasks was significantly faster with green light, including endoscopy setup (43.1 vs. 62.1 s), biopsy sample time (35.8 s vs. 80.1 s), and feeding wire (34.3 vs. 99.1 s)
  • There was no difference in polyp detection rate under the 2 light conditions. However, color detection of anesthesia medication tapes and endoscopic tools was better with dim light.
  • Eye strain score was significantly better with green light compared with dim light (10.3 vs. 4.1)

My take: Use of green light in endoscopy suites is likely beneficial particularly in more technically-demanding procedures. It makes common tasks easier/quicker and with less eye strain.

(A) Endoscopy suite under green light. (B) Endoscopy suite under low light.

Long-term Efficacy and Safety of Upadacitinib for Ulcerative Colitis

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R Panaccione et al. The Lancet Gastroenterology & Hepatology. 2025; 10: 507 – 519. Open Access! Long-term efficacy and safety of upadacitinib in patients with moderately to severely active ulcerative colitis: an interim analysis of the phase 3 U-ACTIVATE long-term extension study

Methods: U-ACTIVATE is an ongoing, 288-week, phase 3, long-term extension study that enrolled patients (n=369) aged 16–75 years with a confirmed diagnosis of moderately to severely active ulcerative colitis; patients who had a clinical response in the induction studies were eligible to enter the U-ACHIEVE maintenance study. Patients not in clinical remission originally randomly assigned to upadacitinib 15 mg were eligible to escalate to upadacitinib 30 mg, those originally randomly assigned to upadacitinib 30 mg continued on upadacitinib 30 mg, and those originally assigned to placebo were eligible to escalate to upadacitinib 15 mg in a masked way

Key findings:

  • In the as-observed population, 84 (71%) of 118 patients receiving upadacitinib 15 mg were in clinical remission at week 48, as were 130 (67%) of 193 receiving upadacitinib 30 mg
  • By week 96, 69 (76%) of 91 patients receiving upadacitinib 15 mg and 104 (74%) of 141 of those receiving upadacitinib 30 mg were in clinical remission
  • The most common adverse events of special interest were hepatic disorder, lymphopenia, creatine phosphokinase elevation, serious infection, neutropenia, and herpes zoster
mNRI indicates modified non-responder imputation analysis response

My take: This study shows a good durable (3 year) response to upadacitinib treatment with both 15 mg and 30 mg dosing.

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