“Is Salt at Fault?” in Inflammatory Bowel Disease

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R Kuang et al. Inflamm Bowel Dis 2023; 29: 140-150. Is Salt at Fault? Dietary Salt Consumption and Inflammatory Bowel Disease

This review looks at the potential role of salt in relation to the epidemiology of inflammatory bowel disease. The general focus is that the prevalence/incidence of IBD has been increasing and there must be environmental/dietary factors involved. Could salt be one of those causal factors or is it merely a temporal association?

Key points:

  • Ultra-processed foods make up more than half of the daily caloric intake in developed countries such as the United States! and Canada and between one-third to one-fifth of diets in middle-income countries such as Brazil and Mexico.. Ultra-processed foods involve “fractioning of whole foods into substances, chemical modifications of these substances, frequent use of cosmetic additives and sophisticated packaging that allow producers to create highly profitable, convenient, and hyperpalatable products.” Ultra-processed foods are typically high in sugar, unhealthy fats, and salt and low in dietary fiber, protein, vitamins, and minerals. They are also calorie dense. For Americans, the primary source of sodium in the diet is from commercially processed foods.
  • At present, the typical American consumes over 40% more salt on a daily basis than is re-commended. Added salt is a key component of UPFs, whose increased consumption has been closely linked to this rise in the IBD incidence. Even though salt is a key component of UPFs, it has received limited attention in the investigation of IBD...Excess salt contributes to greater monocyte and T-cell-driven inflammation and a parallel loss of immunoregulatory mechanisms involving M2 macrophages and Tregs in the Th17 axis.
  • The authors argue that improvement in IBD with exclusive enteral nutrition is another factor indicating a potential role for salt reduction as beneficial. “Although these ultra-processed liquid nutrition formulas were high in sugars, emulsifiers, and carrageenan, they were very low in sodium content.”

My take: It is not clear what impact salt has on IBD. However, too much salt causes problems well beyond hypertension and may contribute to several inflammatory conditions, including IBD, asthma, and rheumatoid arthritis.

Related blog posts:

Unrelated website information: IBD-EII is a website which has tried to organize/summarize some of the more important IBD articles including a timeline of these publications and evidence for specific medications.

Atlanta Botanical Gardens. Garden Nights, Holiday Lights exhibit

Tofacitinib Outperformed Vedolizumab in Anti-TNF-experienced Ulcerative Colitis

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T Straamijer et al. Clin Gastroenterol Hepatol 2023; 21: 182-191. Open Access! Superior Effectiveness of Tofacitinib Compared to Vedolizumab in Anti-TNF-experienced Ulcerative Colitis Patients: A Nationwide Dutch Registry Study

Methods: Adults with ulcerative colitis (UC) previously who failed anti-TNF treatment and initiated vedolizumab (n=83) or tofacitinib (n=65) treatment were identified in the Initiative on Crohn and Colitis Registry in the Netherlands.

Key findings (Vedolizumab is in gray):

  • There was no difference in infection rate or severe adverse events.

My take: Coupled with more recent reassuring safety data on JAK inhibitors, this study makes a strong case for positioning Tofacitinib (or other JAK inhibitor) earlier in patients with moderate-to-severe ulcerative colitis. Given that vedolizumab outperformed adalimumab in a head-to-head study, this indicates that tofacitinib is a very effective therapy.

Related article: B Chen et al. Gastroenterology 2022; 163: 1555-1568. Efficacy and Safety of Ivarmacitinib in Patients With Moderate-to-Severe, Active, Ulcerative Colitis: A Phase II Study This phase 2 study with 146 patients examined the effectiveness of the selective JAK inhibitor Ivarmacitinib found a week 8 clinical response in 46% of those receiving 8 mg per day. The week 8 clinical remission rate was 22%-24% in the treatment groups compared to 5% in the placebo group.

Related blog posts:

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.

POSE 2.0 Procedure for Obesity

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Anyone who follows this blog closely knows my inherent attraction for study acronyms; it is too bad I am not a leading researcher because it would be really fun to come up with some hilarious acronyms.

The Primary Obesity Surgery Endoluminal (POSE) Procedure for the treatment of obesity (GL Nava et al. Clin Gastroenterol Hepatol 2023; 21: 81-89) prospectively enrolled 44 adult patients who underwent “a novel pattern of full-thickness gastric body plications to shorten and narrow the stomach using durable suture anchor pairs.”

Key findings:

  • This procedure used an average of 19 suture anchor pairs, with a mean duration of 37 ± 11 minutes, and was technically successful in all subjects
  • Mean percentage total body weight loss (%TBWL) at 12 months was 15.7% ± 6.8%. >15% TBWL was achieved by 58%
  • Improvements in lipid profile, liver biochemistries, and hepatic steatosis were seen at 6 months
  • Repeat assessment at 24 months (n = 26) showed fully intact plications. No serious adverse events occurred

My take: This study shows that endoscopic therapies for obesity are quite promising. However, endoscopic therapies and bariatric surgery may become 2nd or 3rd line therapies if oral medications are available that can achieve similar success. Though, medications could require indefinite treatment.

Related blog posts:

“What Makes A “Successful” Kasai Portoenterostomy “Unsuccessful”?

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M Matcovici et al. JPGN 2023; 76: 66-71. What Makes A “Successful” Kasai Portoenterostomy “Unsuccessful”?

Methods: This review of a single-center prospective biliary atresia (BA) database examined which factors were associated with long-term success of a Kasai portoenterostomy (KPE). Successful KPE was defined by achieving a postoperative bilirubin of ≤20 µmol/L. Cholangitis was based on Tokyo (Adult) Guidelines (Calculator MD Calc: Tokyo Guidelines for Acute Cholangitis 2018). Explanation of Tokyo Guidelines: Tokyo Classification Cholangitis

Key findings:

  • 90 (67%) achieved clearance of jaundice after KPE. From these 20 (22%) (Cohort A) underwent LT with the remainder continuing with native liver (Cohort B) (median follow-up of 4.15 years)
  • Postoperatively, both cholangitis [any episode, 18/20 (90%) vs 15/70 (21%); P < 0.0001] and portal hypertension (PHT) [gastrointestinal (GI) bleed, 10/20 (50%) vs 2/70 (2.8%); P < 0.0001] were significantly more common in cohort A

My take: The authors assert that “failure is not preordained at KPE but due to recurrent cholangitis and/or symptoms of PHT.” In my view, this study shows an association but not causation of cholangitis/PHT with increased likelihood of KPE failure. It is quite possible that the cholangitis develops in those with suboptimal bile flow; thus, cholangitis (as well as PHT) may be an indicator that the KPE is not working as well, rather than the reason. Yet, it is also likely that episodes of cholangitis exacerbate any underlying problems.

Related blog posts:

Useful Endoscopic Tricks for Stricture Management and Magnets

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JL Yasuda et al. JPGN 2023; 76: 77-79. Measurement of Stricture Dimensions Using a Visual Comparative Estimation Method With Biopsy Forceps During Endoscopy

This quick study looked at using biopsy forceps in 191 endoscopies to estimate esophageal stricture narrowing. Key findings:

  • Lin’s concordance correlation coefficient was 0.92 (95% confidence interval: 0.89–0.94) between the visual diameter estimates and the fluoroscopic stricture measurements.
  • Correlation was strongest for smaller to mid-sized stricture diameters
  • Yellow biopsy forceps open wide to ~6 mm and standard orange biopsy forceps ~7 mm
  • Dimensions of the actual scope can be helpful in estimating a stricture. Some pediatric scope have 5-6 mm diameter and standard scopes ranging from 8.0-9.8 mm

My take: This study shows that commonly available endoscopic tools can be used to more accurately estimate stricture diameter.

Related blog posts:

K Guilcher et al. JPGN Reports 3(4):p e257, November 2022. | DOI: 10.1097/PG9.000000000000025. Open Access! Innovative Makeshift Technique for Removing Ingested Rare Earth Magnets “In this case, a makeshift technique of a prototype magnet in a net attracted the buried magnets within the food bolus and allowed successful retrieval of all intragastric magnets at once.” My take: This is a clever way to co-opt the enemy (the magnets). However, other useful approaches: 1. Many times an endoscopic forceps will attract the magnets 2. Using fluoroscopy, can be helpful in locating difficult to visualize objects

Atlanta Botanical Gardens: Garden Lights, Holiday Lights (with and without 3-D glasses)

Celiac Disease Identified After Family Index Case

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MJ Gould et al. JPGN 2023; 76: 49-52. Characteristics of Pediatric Patients With Celiac Disease Identified Due to an Affected First-Degree Family Member

In this retrospective study, 49 patients were screened due to an affected first-degree relative with celiac disease. They were compared to 178 patients who were screened for other clinical indications. Key findings:

  • Although 51% of patients screened due to an affected first-degree relative were asymptomatic, their disease histology and TTG levels were as severe as those screened for symptoms suggestive of celiac disease (in the comparison group 16% were asymptomatic). 

Comments:

  1. “Previous studies have shown that asymptomatic adolescents and those diagnosed with CD by serologic screening are less likely to adhere strictly to a GFD when compared to younger children and adults diagnosed because of classical symptoms” (Dig Dis Sci. 2008 Jun; 53(6): 1573–1581).”
  2. Some individuals who are thought to be asymptomatic, clinically improve with a gluten free diet (GFD). In one study, “the GFD group also had reduced indigestion (P=.006), reflux (P=.05), and anxiety (P=.025), and better health, based on the visual analog scale (P=.017), than the gluten-containing diet group” (Gastroenterology  2014 Sep;147(3):610-617).

My take: In this study, being asymptomatic (identified due to affected first-degree relative) was NOT associated with milder celiac disease based on serology or histology.

Relate blog posts:

Garden Lights, Holiday Lights at Atlanta Botanical Gardens

Safety Net for Celiac Disease?

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JA Murray, JA Syage et al.Gastroenterol 2022; 163: 1510-1521. Open access! Latiglutenase Protects the Mucosa and Attenuates Symptom Severity in Patients With Celiac Disease Exposed to a Gluten Challenge

Background: Latiglutenase (IMGX003) is an investigational dual-enzyme drug candidate that acts to degrade gluten in vivo when consumed with a meal. The authors note that “despite strict adherence to a GFD, about half of CD patients show evidence of persistent small intestinal mucosal injury (Marsh grades II–III);’ thus, there is a need to improve treatment with other measures in addition to diet.

Methods: 43 patients (IMGX003, n = 21; placebo, n = 22) completed this double blind and placebo controlled study which assessed the efficacy and safety of a 1200-mg dose of IMGX003 in patients with celiac disease (CD) exposed to 2 g of gluten per day for 6 weeks study

Key findings:

  • In IMGX003-treated patients, there was less damage to mucosa. The mean change in the ratio of villus height to crypt depth (primary endpoint) for IMGX003 vs placebo was –0.04 vs –0.35 (P = .057). The mean change in the density of intraepithelial lymphocytes (secondary endpoint) for IMGX003 vs placebo was 9.8 vs 24.8 cells/mm epithelium (P = .018). 
  • Measurements of gluten-immunogenic peptides (GIP) in urine indicated 95% gluten degradation in the stomach by latiglutenase.

The 2 g dose per meal of gluten allowed used in the study, “would likely substantially exceed that accidently occurring while on a GFD, 4 supporting such an approach for management for gluten-triggered symptoms in treated patients.”

Graphical abstract:

In both the placebo and IMGX003 groups, there was an increases in symptoms, but this was blunted in the treated group–Figure 2:

My take: This study shows the potential for latiglutenase to act as a ‘safety net’ to protect from CD from accidental gluten exposure. The findings reinforce the idea that this agent is not likely to be effective in the absence of gluten restriction. As an aside, I would be interested in finding out whether patients with presumed non-celiac gluten sensitivity would improve on this therapy.

Related blog posts:

IBD Updates: Understanding Newest IBD Therapies for Kids- Bowel Sounds, Hispanic Patients with IBD, More on Intestinal Ultrasound

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Bowel Sounds Link: Joel Rosh talks small molecules and biologics

This is another good chat. Dr. Rosh provides a lot of information about the newest IBD agents. Overall, the episode indicates a very enthusiastic experience with IL-23 targeting agents like risankizumab (perhaps the ‘Michael Jordan’ of biologics) and with JAK agents like tofacitinib and upadacitinib. Dr. Rosh’s experience with regard to safety of these newer agents has been very positive. For tofacitinib, the typical dosing alluded to in the podcast was 10 mg twice a day (not three times a day). The potential adverse effects, though unlikely in the pediatric population, are carefully discussed with families and monitored.

So far, Dr. Rosh has not found a niche for ozanimod. In addition, he briefly discusses therapeutic drug monitoring. With regard to using vedolizumab as a first-line agent for ulcerative colitis, he often uses the VARSITY study (BE Sands et al NEJM 2019; 381: 1215-26) to justify this to payers. There is a sad element to the podcast though –Dr. Rosh admits to being a lifelong Mets fan!

Related blog posts:

NH Nguyen et al. Clin Gastroenterol Hepatol 2023; 21: 173-181. Open Access! Effectiveness and Safety of Biologic Therapy in Hispanic Vs Non-Hispanic Patients With Inflammatory Bowel Diseases: A CA-IBD Cohort Study

Key findings in this retrospective study with 240 Hispanic patients:

  • Within 1 year of biologic initiation, Hispanic patients had higher rates of hospitalizations (31% vs 23%; adjusted hazard ratio [aHR], 1.32; 95% CI, 1.01–1.74) and IBD-related surgery (7.1% vs 4.6%; aHR, 2.00; 95% CI, 1.07–3.72), with a trend toward higher risk of serious infections (8.8% vs 4.9%; aHR, 1.74; 95% CI, 0.99–3.05).
  • The authors state “these findings suggest that biologic agents may not be as effective or safe in Hispanic patients as they are in non-Hispanic Caucasians… Besides biological factors, socioeconomic factors related to costs and access to care, which contribute to delayed initiation of biologics, and/or limited postinitiation monitoring, leading to higher rates of unplanned health care utilization.”

T Kucharzik et al. Clin Gastroenterol Hepatol 2023; 21: 153-163. Open Access! Early Ultrasound Response and Progressive Transmural Remission After Treatment With Ustekinumab in Crohn’s Disease (STARDUST study)

Key findings:

  • IUS showed that ustekinumab-treated CD patients achieved progressive IUS response (46.3%) and transmural remission (24.1%) through week 48, with a more robust response in the colon and biologic-naive patients
  • Fair/moderate reliability (κ = 0.21–0.51) was observed between week 4 IUS response and week 48 overall endoscopic response and fecal calprotectin/complete biomarker outcomes.