Validated SEMA-CD Score For Crohn’s Disease

J Adler et al. Inflamm Bowel Dis 2022; Open Access! Validating the Simplified Endoscopic Mucosal Assessment for Crohn’s Disease: A Novel Method for Assessing Disease Activity

“The SEMA-CD is scored by assigning a numerical value ranging from 0 (endoscopic remission) to 4 (severe disease) for each bowel region (ileum and colon). The overall colon is scored as a whole based on the most severe colonic segment.  The number of colonic segments with any degree of active disease is recorded, regardless of the severity of individual segments. The overall colon score is then multiplied by the number of involved colonic segments, and the result is added to the ileum score.”

Related blog post: The Really Simplified Endoscopy Scoring

Understanding FDA Approval of Vonoprazan-Based Therapies for Helicobacter Pylori

Pharmacy Times (5/4/22): FDA Approves Pair of Vonoprazan Treatments for Helicobacter Pylori Infection

“The (FDA) has approved 2 vonoprazan-based medications for the treatment of Helicobacter pylori (H. pylori) infection.

Phathom Pharmaceuticals announced the approvals of both the Voquezna Triple Pak (vonoprazan, amoxicillin, clarithromycin) and Voquezna Dual Pak (vonoprazan, amoxicillin) based on positive safety and efficacy data from the phase 3 PHALCON-HP trial.”

WD Chey et al. Gastroenterol 2022; 163: 608-619. Open Access! Vonoprazan Triple and Dual Therapy for Helicobacter pylori Infection in the United States and Europe: Randomized Clinical Trial

Key findings from this randomized, controlled trial with treatment-naive 1046 adults:

  • In all patients, vonoprazan triple and dual therapy were superior to lansoprazole triple therapy (80.8% and 77.2%, respectively, vs 68.5% (both superior)
  • In patients with clarithromycin resistance, vonoprazan triple therapy was effective in 65.8%, dual therapy in 69.6%, vs lansoprazole triple therapy 31.9% (both superior)
  • Vonoprazan increases intragastric pH rapidly “and maintains it to a greater degree than PPI; this has been associated with higher H pylori eradication rates” (in prior studies as well)

The associated editorial: CA Fallone (Open Access!) The Current Role of Vonoprazan in Helicobacter pylori Treatment

Based on this new information, the author proposes the treatment algorithm below and notes that “the role of increased acid suppression by PPI substitution with vonoprazan should be examined in other H pylori regimens.” The author favors bismuth quadruple therapy in those with clarithromycin resistance as non-bismuth quadruple therapy utilizes an unnecessary antibiotic (clarithromycin).

Other points:

  • Metronidazole resistance is fairly common, but bismuth quadruple therapy can overcome much of the metronidazole resistance
  • Levofloxacin resistance is quite high in certain regions and should only be used with caution, given recent warnings from the US Food and Drug Administration of aortic rupture in susceptible individuals
  • Rifabutin can cause some bone marrow suppression

My take: With the more widespread availability of susceptiblity testing (beyond clarithromycin), I anticipate more targeted treatments. At the same time, vonoprazan-based treatments are likely to be important in increasing eradication rates.

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.

Collaboration Needed for Lock Therapy in Intestinal Failure

On Tuesday, this blog asked: Who is Going to do POEM (Peroral Endoscopic Myotomy) in Children? In the U.S., Boston Children’s offers this treatment option: Peroral Endoscopic Myotomy (POEM). This link explains the procedure and includes a video (also on YouTube) with Peter Ngo .

—————–

In 2018, Belcher pharmaceuticals managed to get the FDA to designate Ethanol as an orphan drug with a subsequent increase in cost to ~$10,000 for a 10-vial pack (10-day supply) (Related post: FDA ‘Safety Initiative’ Now Means an Ounce of Ethanol Costs $30,000). As such, many (?most) children with intestinal failure (IF) no longer have access to this therapy which prevents life-threatening infections to their central lines.

A recent retrospective study (R Josyabhata et al. JPGN 2022; 75: 304-307. Sodium Bicarbonate Locks May Be a Safe and Effective Alternative in Pediatric Intestinal Failure: A Pilot Study) examined the use of sodium bicarbonate lock therapy (SBLT) as an alternative to ethanol in four children. This study was prompted by a clinical trial in hemodialysis patients which demonstrated a reduction in catheter-related bloodstream infections (CRBSI). None of the four patients had a CRBSI.

My take: A much larger multi-center study will be needed to determine if SBLT is worthwhile.

Related blog posts:

Related articles:

A Guz-Mark et al. JPGN 2022; 75: 293-298. The Variable Response to Teduglutide in Pediatric Short Bowel Syndrome: A Single Country Real-Life Experience. The effectiveness of teduglutide, which likely costs more than $400,000 per year in most patients, was examined in a real-life retrospective study from Israel with 13 patients. Response to treatment (>20% reduction in parenteral nutrition) was observed in 8 patients (62%) and 2 patients were able to stop parenteral nutrition.

K Culbreath et al. JPGN 2022; 75: 345-350. Antibiotic Therapy for Culture-Proven Bacterial Overgrowth in Children With Intestinal Failure Results in Improved Symptoms and Growth This article describes outcomes of 104 children with intestinal failure who underwent endoscopy and had duodenal cultures sent to identify bacterial overgrowth/susceptibility/targeted antibiotics. This information was associated with fewer symptoms and better growth. The methods section provides detailed information on collection and handling of specimens (which could be helpful for those trying to implement this strategy). However, there is not a standardized protocol for duodenal cultures to detect bacterial overgrowth.

Carter Lake (not far from Seward, AK)

Who is Going to do POEM (Peroral Endoscopic Myotomy) in Children?

AA Mencin et al. JPGN 2022; 75: 231-236. Peroral Endoscopic Myotomy (POEM) in Children: A State of the Art Review

This is a terrific review of POEM; it explains the procedure technique (with pictures), outcomes, indications and adverse events. The paper indicates that more than 300 children (as young as 11 months) have had POEM in published studies with good outcomes.

Interestingly, the authors state that 20-40 procedures “should be performed for competency and that 60 are required to achieve mastery.” Also, long-term data are lacking.

This paper extensively references a White Paper summary: DJ Scott et al. Gastrointestinal Endoscopy 2014; 80: 1-15. Open Access! Per-oral endoscopic myotomy white paper summary

My take: POEM has good data supporting its use, especially in adults. Still, it will be quite difficult for pediatric gastroenterologists to acquire sufficient expertise to do this procedure.

Related blog posts:

“Exit Glacier” in Kenai Fjords National Park. This picture shows how much the glacier has retreated since 2005 due to global warming (the ice used to extend to this sign).

Eat More Chicken? (for EoE)

JB Wechsler et al. Clin Gastroenterol Hepatol 2022; 20: 1748-1756. A Single-Food Milk Elimination Diet Is Effective for Treatment of Eosinophilic Esophagitis in Children

Design: A prospective observational single-center study in 41 children with EoE treated with the 1-food elimination diet (1FED). Upper endoscopy with biopsies was performed after 8 to 12 weeks of treatment. The primary end point was histologic remission, defined as fewer than 15 eosinophils per high-power field.

Key findings:

  • Histologic remission occurred in 21 (51%) children, with a decrease in peak eosinophils per high-power field from a median of 50
  • Endoscopic abnormalities improved in 24 (59%) patients, while symptoms improved in 25 (61%). Improved symptoms included chest pain, dysphagia, and pocketing/spitting out food
  • Interestingly, in terms of all symptom resolution, this was higher in the group of nonresponders 8 (40%) than in the responders 4 (19%)
  • Younger patients (mean 7 yrs vs 12 yrs) and patients with IgE-mediated food allergies tended to be more likely to fail dairy elimination in this study
  • One key caveat is that most patients continued PPI during study; thus it is unknown if stopping a PPI before starting dairy elimination would have changed treatment response. 90% of patients were receiving PPIs at enrollment

My take: This study should prompt more widespread use of dairy elimination as a first line treatment prior to consideration of medications for long-term treatment. This study also reinforces the concept that symptom improvement remains an inadequate indicator of response. Perhaps, Chick-Fil-A marketing needs to be used for our EoE patients to shun cows (cow’s milk in this case).

Related blog posts:

Kenai Fjords National Park, near Seward Alaska

What’s New in the Treatment of Hepatitis B

P Martin et al. Clin Gastroenterol Hepatol 2022; 20: 1766-1775. Open access! Treatment Algorithm for Managing Chronic Hepatitis B Virus Infection in the United States: 2021 Update

This article provides an updated treatment algorithm with many changes since 2015.

Key points:

New terminology. The authors provide updated terminology. The term ‘immune tolerant’ is losing favor. “There is also evidence that during the immune tolerant phase virologic events occur, such as integration of viral DNA into the host genome, which may help set the stage for the subsequent development of HCC.” As such, the new terminology focuses on “describing the 2 main characteristics of chronicity, infection alone and infection with evidence of ongoing hepatic inflammation (ie, hepatitis).” (See below)

TAF preferred over TDF. “The 4 first-line therapies available for managing CHB infection in the United States are peginterferon alfa-2a, entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF)….It is the opinion of most—but not all—members of the panel that when antiviral therapy is contemplated, TAF is preferred over TDF because of the lower risks of renal or bone side effects and higher likelihood of ALT normalization through 48 weeks.” For decompensated cirrhosis, TAF and peginterferon are NOT recommended.

Long term treatment is the rule (not the exception). “HBeAg-positive patients with evidence of less extensive fibrosis (<F3) should be treated long-term, even after HBeAg seroconversion and virologic suppression because of the risks of virologic relapse55 and ALT flares, except when treatment is initiated solely for the purpose of prevention of vertical transmission…For HBeAg-negative patients without HBsAg seroconversion, the panel does not recommend stopping treatment.”

Monitoring. “Primary nonresponse to ETV, TDF, or TAF is rare; therefore, any patients who are not responsive to these agents after 12 to 24 weeks should be evaluated for compliance.”

Table 1 (see below) summarizes treatment recommendations. In almost all patients with HBV, if there is elevated ALT, treatment is recommended.

Terminology:

Table for Treatment Recommendations:

In the article, more information is available, including recommendations
for treatment in the setting of HIV coinfection

My take: Forget about “immunotolerant” HBV. Until better treatments emerge, patients with HBV and elevated liver enzymes are likely to need long-treatment if using TAF, TDF or entecavir.

Related blog posts:

New Federal Safety Standard for Magnets to Prevent Deaths and Serious Injuries

9/7/22 CPSC Approves New Federal Safety Standard for Magnets to Prevent Deaths and Serious Injuries from High-Powered Magnet Ingestion

Thanks to Ben Gold for this reference

  • “In an effort to reduce the risk of children and teens experiencing serious, even life-threatening injuries from swallowing dangerous, small high-powered magnets, the U.S. Consumer Product Safety Commission (CPSC) voted to approve a new federal safety standard for magnets on September 7, 2022.”
  • “The new mandatory federal standard requires loose or separable magnets in certain magnet products to be either too large to swallow, or weak enough to reduce the risk of internal injuries when swallowed; specifically, if the magnets fit in a small parts cylinder, then they must have a flux index of less than 50 kG2 mm2.”
  • “CPSC estimates 26,600 magnet ingestions were treated in hospital ERs from 2010 through 2021, and cases have been rising annually since 2018. CPSC is aware of seven deaths involving the ingestion of hazardous magnets (including two outside of the United States), the majority of these incidents likely involved magnet sets.”
  • “CPSC urges anyone who may own these magnets and magnet sets to discard them to protect children who may come into contact with them and unintentionally ingest them. “

My take: This is a step in the right direction.

Related posts:

Knik Glacier Ice Field, AK

Overdiagnosis of Milk Allergy in Infancy and New Consensus Recommendations

Fun story form Avi Yemini on Twitter (98 second video): “You can never get tired of hearing this story about Queen Elizabeth II”

——————————————————-

HI Allen et al. Clin Exp Allergy 2022; 52: 848-858. https://doi.org/10.1111/cea.14179. Open Access: Detection and management of milk allergy: Delphi consensus study

This study reviewed the topic of milk allergy (both IgE-mediated and non-IgE mediated milk allergy) and provides consensus recommendations from 28 non-conflicted multidisciplinary international experts.

Key points:

  • “Milk allergy diagnosis can be difficult, making the condition vulnerable to overdiagnosis – and formula milk company sponsorship of milk allergy guidelines, their authors and healthcare professional education is thought to contribute to milk allergy overdiagnosis…Prescriptions for specialized formula used by bottle-fed infants with cow’s milk allergy have increased … expected volumes by up to 10-fold.”
  • “Consensus was reached that milk allergy does not need to be considered for changes to colour, frequency or consistency of stool, aversive feeding, occasional spots of blood in stool, nasal or respiratory symptoms, in the absence of a temporal relationship with milk protein ingestion. Exceptions to this were biopsy-proven eosinophilic gastrointestinal disorders or protein-losing enteropathy or, in a child ingesting milk protein, faltering growth or daily visible blood in stools”
  • “Participants noted that visible blood in the stool in an exclusively breastfed infant [has] many possible causes including infection and fissures….and the condition is generally of short duration without serious health consequences”

My take: Milk allergy is overdiagnosed in infancy. This guideline supports a more supportive treatment approach. Because breastmilk is hypoallergenic, maternal dietary restriction may be more harmful than helpful in those with mild symptoms (especially if not having trouble with growth or with hypoalbuminemia). Table 1 below lists some of the most important of the 38 consensus recommendations.

Related blog posts:

Boat view near Kenai Fjords National Park, AK

Predicting Risk of Celiac Disease in High-risk Families

CR Meijer et al. Gastroenterol 2022; 163: 426-436. Open access: Prediction Models for Celiac Disease Development in Children From High-Risk Families: Data From the PreventCD Cohort

B Lebwohl, L Greco. Gastroenterol 2022; 163: 368-369 (editorial). Open access: Can We Predict the Onset of Celiac Disease?

Design: “In this study, the investigators analyze long-term follow-up data from the PreventCD trial, a randomized trial of infants [n=944] with a first-degree relative with CD that was designed to test the strategy of low-dose gluten introduction at age 4 months. The trial did not show that this strategy reduced the risk of CD development,7 but the abundant data collected during this trial have allowed these investigators to study risk factors for the development of CD among the trial participants.” The median f/u was 8.3 yrs.

Key points from study and editorial:

  • 135/944 (14%) children developed CD (mean age, 4.3 years)
  • CD developed significantly more often in girls (P = .005) and in Human Leukocyte Antigen (HLA)-DQ2 homozygous individuals (8-year cumulative incidence rate of 35.4%
  • Prediction application calculator with screening recommendations https://hputter.shinyapps.io/preventcd/. This screening calculator generally recommends screening every 6 months for those at greastest risk and every 12 months for those at lower risk.

HLA testing in this setting has historically been performed primarily due to its excellent negative predictive value. Because HLA DQ2 and DQ8 are present in nearly 100% of people with CD, the primary value of its use has been in ruling out CD when an individual is found to have neither haplotype. This study shows some usefulness in predicting the likelihood of CD.

My take: This study showed 14% of high-risk children developed celiac disease and the number is likely to escalate with more time. In first-degree relatives, checking HLA-DQ2/8–typing may help determine frequency of screening in asymptomatic individuals –though simply choosing to screen every 1-2 years would be a reasonable alternative.

It should be noted that current expert guidelines provide divergent advice; “NASPGHAN recommends that asymptomatic children in high-risk groups (including first-degree relatives) be screened, 4 but the United States Preventive Services Task Force concluded that the evidence is insufficient to warrant recommending for or against screening asymptomatic individuals.”

Related blog posts:

Westchester Lagoon, off Tony Knowles Coastal Trail. Anchorage, AK

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.