Positioning Radiology Tests for GI Bleeding

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N Sengupta et al. Am J Gastroenterol 2024; 119: 438-449. Open Access! The Role of Imaging for Gastrointestinal Bleeding: Consensus Recommendations From the American College of Gastroenterology and Society of Abdominal Radiology. Thanks to Dr. Benjamin Gold for this reference.

This article was jointly published: Radiology 2024; 310(3):e232298

This article focuses on GI bleeding in adults; it has a lot of useful information about the advantages, disadvantages, techniques and performance date of numerous radiology tests which can help sort out GI bleeding.

CTE identification of a Dieulafoy’s lesion (from Figure 4)
CTE here shows a slowly bleeding angioectasia (arrow), most conspicuous on the delayed phase.

Some of the recommendations for Overt Lower GI Bleeding:

CT Angiography:

Catheter Angiography:

99mTc-RBC Scan

For Suspected Small Bowel Bleeding:

CT Enterography (uses oral contrast). Technique: CTE should be performed using multiphase technique in patients older than 40 years of age where vascular lesions are a common cause for bleeding.

Meckel’s Scan “A Meckel scan can be considered to identify the cause of unexplained intermittent GI bleeding in children and adolescents after negative endoscopic evaluation, including capsule endoscopy if available, and cross-sectional evaluation of the small bowel.”

Radiology compared to capsule endoscopy and balloon-assisted endoscopy The authors discuss the advantages and limitations of radiologic testing versus capsule endoscopy and balloon-assisted endoscopy for small bowel bleeding is provided in Appendix S5

My take: This article provides a good update/review on useful radiologic imaging for GI bleeding. For pediatric GI bleeding, the etiologies are much different and many patients should be evaluated with a Meckel’s scan prior to panendoscopy (depending on the clinical presentation).

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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.

Relooking at 6-Year Data of Maralixibat for Alagille Syndrome

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BE Hansen et al. Hepatology 2024; 79: 1279-1292. Open Access! Event-free survival of maralixibat-treated patients with Alagille syndrome compared to a real-world cohort from GALA

This study compared “6-year outcomes from maralixibat trials with an aligned and harmonized natural history cohort from the Global ALagille Alliance (GALA) study.”

Based on a quick review, some the data appears to overlap a recent report in the same journal: RJ Sokol et al. Hepatology 2023; 78: 1698-1710. Open Access! Predictors of 6-year event-free survival in Alagille syndrome patients treated with maralixibat, an ileal bile acid transporter inhibitor (See blog post: Six Year Data for IBAT Inhibitor Treatment for Alagille Syndrome).

In the current study, “event-free survival, defined as the time to first event of manifestations of portal hypertension (variceal bleeding, ascites requiring therapy), surgical biliary diversion, liver transplant, or death, was analyzed by Cox proportional hazards methods.”

Key findings:

  • Event-free survival in the maralixibat cohort (n=84) was significantly better than the GALA cohort (n=469) (HR, 0.305)
  • Transplant-free survival showed similar results (aHR, 0.33)

In their discussion, the authors note that much of the improvement in event-free survival is due to improvement in pruritus which is a main indication for liver transplantation. They speculate that improvement in event-free survival is also related to more broad-based clinical improvement (observed in ICONIC study), perhaps due to reduction in retained hepatic bile acids.

One of the limitations, reliance on a historical control, is discussed. “Historical control comparison is useful when there are ethical concerns regarding the recruitment of patients for long-term control arms requiring several years of study in life-threatening or debilitating diseases.”

My take: In this real-world comparison, Maralixibat, clearly was associated with improved outcomes. How much of this was due to relief of intractable pruritus and how much of this may be due to other biologic factors remains uncertain.

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Video of Intussusception Reduction

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R Michael, J Tozer. N Engl J Med 2024;390: e53. Small-Bowel Intussusception in an Adult

The authors describe the presentation/resolution of a 57 yo with a small bowel intussusception due to a fibroblastic polyp lead point.

Video: Reduction of Intussusception (may be behind a paywall)

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Dupilumab (Dupixent) for Young Children with Eosinophilic Esophagitis (Published Data)

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M Chehade et al. NEJM 2024;390:2239-2251 Dupilumab for Eosinophilic Esophagitis in Patients 1 to 11 Years of Age

This study provides published data that has been referenced previously at time of FDA approval and prior meetings (see posts: Dupixent Approved in Younger Children (15 kg+), Dupixent for Eosinophilic Esophagitis (1-11 yrs) and Clinical Diagnosis of Rumination from DDW Tweets).

Methods:

  • Part A -In this phase 3 trial, we randomly assigned, in a 2:2:1:1 ratio, patients 1 to 11 years of age (n=102) with active eosinophilic esophagitis who had had no response to proton-pump inhibitors to 16 weeks of a higher-exposure or lower-exposure subcutaneous dupilumab regimen or to placebo (two groups)
  • Part B- At the end of Part A, eligible patients in each dupilumab group continued the same regimen and those in the placebo groups were assigned to higher-exposure or lower-exposure dupilumab for 36 weeks  

Key findings:

  • In Part A, histologic remission occurred in 25 of the 37 patients (68%) in the higher-exposure group, in 18 of the 31 patients (58%) in the lower-exposure group, and in 1 of the 34 patients (3%) in the placebo group
  • The higher-exposure dupilumab regimen led to significant improvements in histologic, endoscopic, and transcriptomic measures as compared with placebo
  • The improvements in histologic, endoscopic, and transcriptomic measures between baseline and week 52 in all the patients were generally similar to the improvements between baseline and week 16 in the patients who received dupilumab in Part A
  • Similar adverse effects were noted across all groups. There was an increased rate (at least 10%) of COVID infections in participants receiving dupilumab whereas the incidence of vomiting was at least 10 percentage points lower among patients who received dupilumab (either group) than among those who received placebo 

My take: Dupilumab is an effective option for eosinophilic esophagitis.

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Do PPIs Increase the Risk of Eosinophilic Esophagitis in Patients with Esophageal Atresia?

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TC Tang et al. JPGN 2024;78:1317–1328. Proton pump inhibitors, antibiotics, and atopy increase the risk of eosinophilic esophagitis in children with esophageal atresia

In this retrospective study (2005-2020) with 184 children, key findings:

  • Of 184 children with EA, 46 (25%) developed EoE during this period
  • Children with EoE and EA received PPI for significantly higher durations (p = .018) and at significantly higher cumulative doses (p = .017) than controls. (Controls were children with EA who did not develop EoE)
  • Food allergy (adjusted odds ratio [aOR], 7.317, family history of atopy (aOR, 3.504), and infantile antibiotic exposure (aOR, 1.040) were also significantly associated with an increased risk of developing EoE in the EA cohort

Discussion: “This is congruent with the emerging evidence in the general pediatric population that there is an increased risk of EoE development in individuals who undergo acid suppressive therapy. A possible explanation for these findings is that acid suppressants inhibit gastric parietal cell function and elevate the gastric pH, thereby impairing peptic digestion of dietary allergens, potentiating sensitization, and facilitating the development of allergic diseases like EoE.” Other potential explanations could include PPIs could increase mucosal permeability and/or contribute to dysbiosis.

“Hence, the routine use of PPIs for the first year of life as recommended by the current guidelines may need to be revisited..”

My take: This study shows a clear association of PPIs with development of EoE in this cohort. Due to the study design, it is difficult to be confident regarding causality due to possible selection bias (patients who received PPIs may be those with more predisposition to EoE). Nevertheless, this study suggests that prolonged use of PPIs, even in groups at risk for reflux damage, needs to be carefully considered and possibly directed by objective markers of reflux.

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Arches National Park

Expert Advice on Gluten Introduction and Risk of Celiac Disease

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H Szajewska et al. JPGN 2024; https://doi.org/10.1002/jpn3.12280. Open Access! Early diet and the risk of coeliac disease. An update 2024 position paper by the ESPGHAN special interest group on coeliac disease

Key points:

  • Breastfeeding, whether any amount, exclusive, or of any duration, does not reduce the risk of developing CD
  • Introducing gluten into an infant’s diet at any time between completed 4 months (≥17 weeks) and 12 months of age does not affect the cumulative incidence of CD

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Survodutide, Dual Glucagon Receptor/GLP-1 Receptor Agonist, for MASH (Phase II Trial)

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AJ Sanyal et al. NEJM 2024; DOI: 10.1056/NEJMoa2401755. A Phase 2 Randomized Trial of Survodutide in MASH and Fibrosis

Background/Methods: “Dual agonism of glucagon receptor and glucagon-like peptide-1 (GLP-1) receptor may be more effective than GLP-1 receptor agonism alone for treating metabolic dysfunction–associated steatohepatitis (MASH). The efficacy and safety of survodutide (a dual agonist of glucagon receptor and GLP-1 receptor) in persons with MASH and liver fibrosis” was studied in “48-week, phase 2 trial, we randomly assigned adults with biopsy-confirmed MASH.” (n=293)

“Dual agonism of glucagon receptor and GLP-1 receptor may be more effective than GLP-1 receptor monoagonism for treating MASH, because the extrahepatic benefits of GLP-1 receptor agonism (glucose control, reduced appetite, and weight loss) are combined with direct hepatic effects (increased energy expenditure, lipolysis, and mobilization of hepatic fat) associated with glucagon receptor agonism.”

Key findings:

  • Improvement in MASH with no worsening of fibrosis occurred in 47% of the participants in the survodutide 2.4-mg group, 62% of those in the 4.8-mg group, and 43% of those in the 6.0-mg group, as compared with 14% of those in the placebo group
  • A decrease in liver fat, assessed by MRI-PDFF, content by at least 30% occurred in 63% of the participants in the survodutide 2.4-mg group, 67% of those in the 4.8-mg group, 57% of those in the 6.0-mg group, and 14% of those in the placebo group; improvement in fibrosis by at least one stage occurred in 34%, 36%, 34%, and 22%, respectively. 
  • Adverse effects were more frequent with survodutide than with placebo included nausea (66% vs. 23%), diarrhea (49% vs. 23%), and vomiting (41% vs. 4%); serious adverse events occurred in 8% with survodutide and 7% with placebo.
Primary Endpoint at 48 weeks. The primary end point was histologic improvement (reduction) in metabolic dysfunction–associated steatohepatitis (MASH) with no worsening of fibrosis at week 48.

The discussion notes that “in a phase 2 trial, treatment with the GLP-1 receptor monoagonist semaglutide resulted in a significantly higher percentage of patients with MASH resolution than placebo but not in a significantly higher percentage of patients with improvement in fibrosis stage.26” Thus, the improvement in fibrosis, which was seen in this study with survodutide,will need to be examined in future studies.

My take: Earlier this year, the selective thyroid hormone receptor beta agonist resmetirom gained conditional approval from the Food and Drug Administration as the first pharmacotherapy for MASH with moderate-to-advanced liver fibrosis.5  It looks like there will be a number of pharmacologic agents available in the coming years. Cost and availability will be ongoing concerns. In addition, determining when/how these agents will be used in the pediatric population will not be clear for quite a long time.

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Should Vedolizumab Be Used as a First Line Agent for Crohn’s Disease?

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B Bokemeyer et al. Inflamm Bowel Dis 2024; 30: 746-756.

Methods: 3277 adult biologically-unexposed CD patients starting therapy with VEDO or anti-TNF were consecutively enrolled in 45 IBD centers across Germany (2017-202). This was a non-randomized, observational study with prospectively collected data.

Findings:

  • Anti-TNF agents had higher induction clinical remission rates compared to vedolizumab: 73.9% 56.3% vs, P < .05
  • Vedolizumab (VEDO) had higher long-term clinical remission rates: clinical remission after 2 years was significantly better for VEDO compared with anti-TNF, 74.2% vs 44.7%; P < .05. This was associated with a much better treatment persistent rate. The switch rate for VEDO was 17% compared with 44% for anti-TNF agents.
  • Among week 14 responders, VEDO 2-year clinical remission rates were 88.6% compared to 45.8% (P < .00001) for anti-TNF agents

The discussion describes the strengths and limitations of this study. As it is not a randomized control trial, there can still be selection bias and confounding even with propensity scoring that was done in this study. The authors note that in a prior analysis of RCTs comparing infliximab to vedolizumab in CD patients, that infliximab had higher efficacy for induction and maintenance, though the clinical remission rates were only modestly improved at 1 year. (L Peyrin-Biroulet et al. BMC Gastroenterol 2022; 22: 291).

Recent expert guidance (2024) has favored infliximab and risankizumab over other advance therapies in CD patients who have not had previous biologic therapies (see: Comparative Evidence and Positioning Advance Therapies for Inflammatory Bowel Disease).

My take: This study shows that vedolizumab is a good advanced therapy for patients with Crohn’s disease without prior therapy. Among those with a clinical response at 14 weeks, the treatment durability was particularly impressive in this cohort.

It would be great to see an RCT in children with CD comparing IFX to VEDO. Treatment persistence is even more important in younger patients.

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Semaglutide Keeps Weight Off at Four Year Mark

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NBC News 5/14/24: Wegovy users keep weight off for 4 years, new analysis finds

“The 17,604-patient trial tested Wegovy not for weight loss but for its heart protective benefits for overweight and obese patients who had preexisting heart disease but not diabetes. Participants were not required to track diet and exercise because it was not an obesity study…”

“Patients in the trial, called Select, lost an average of nearly 10% of their total body weight after 65 weeks on Wegovy. That percentage weight-loss was roughly sustained year-on-year until the end of about four years, where weight loss stood at 10.2%…”

“A third new analysis on Select published by Novo on Tuesday showed that the heart protective benefits of Wegovy to patients in the trial occurred regardless of their weight before starting on the drug and regardless of how much weight they lose on it.”

“The weight loss in the heart trial was less than the average of 15% weight loss in earlier Wegovy obesity studies”

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