Author Archives: gutsandgrowth

About gutsandgrowth

I am a pediatric gastroenterologist at GI Care for Kids (previously called CCDHC) in Atlanta, Georgia. The goal of my blog is to share some of my reading in my field more broadly. In addition, I wanted to provide my voice to a wide range of topics that often have inaccurate or incomplete information. Before starting this blog in 2011, I would tear out articles from journals and/or keep notes in a palm pilot. This blog helps provide an updated source of information that is easy to access and search, along with links to useful multimedia sources. I was born and raised in Chattanooga. After graduating from the University of Virginia, I attended Baylor College of Medicine. I completed residency and fellowship training at the University of Cincinnati at the Children’s Hospital Medical Center. I received funding from the National Institutes of Health for molecular biology research of the gastrointestinal tract. I have authored numerous publications/presentations including original research, case reports, review articles, and textbook chapters on various pediatric gastrointestinal problems. Currently, I am the vice chair of the section of nutrition for the Georgia Chapter of the American Academy of Pediatrics. In addition, I am an adjunct Associate Clinical Professor of Pediatrics at Emory University School of Medicine. Other society memberships have included the American Academy of Pediatrics, the Food Allergy Network, the American Gastroenterology Association, the American Association for the Study of Liver Diseases, and the Crohn’s and Colitis Foundation. As part of a national pediatric GI organization called NASPGHAN (and its affiliated website GIKids) I have helped develop educational materials on a wide-range of gastrointestinal and liver diseases which are used across the country. Also, I have been an invited speaker for national campaigns to improve the evaluation and treatment of gastroesophageal reflux disease, celiac disease, eosinophilic esophagitis, hepatitis C, and inflammatory bowel disease (IBD). Some information on these topics has been posted at my work website, www.gicareforkids.com, which has links to multiple other useful resources. I am fortunate to work at GI Care For Kids. Our group has 18 physicians with a wide range of subspecialization, including liver diseases, feeding disorders, eosinophilic diseases, inflammatory bowel disease, cystic fibrosis, DiGeorge/22q, celiac disease, and motility disorders. Many of our physicians are recognized nationally for their achievements. For many families, more practical matters include the following: – 14 office/satellite locations – physicians who speak Spanish – cutting edge research – on-site nutritionists – on-site psychology support for abdominal pain and feeding disorders – participation in ImproveCareNow – office endoscopy suite (lower costs and easier scheduling) – office infusion center (lower costs and easier for families) – easy access to nursing advice (each physician has at least one nurse) I am married and have two sons (both adults). I like to read, walk/hike, bike, swim, and play tennis with my free time. I do not have any financial relationships with pharmaceutical companies or other financial relationships to disclose. I have participated in industry-sponsored research studies.

Understanding FDA Approval of Vonoprazan-Based Therapies for Helicobacter Pylori

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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.

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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.

Collaboration Needed for Lock Therapy in Intestinal Failure

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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 .

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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?

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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.

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“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).

More Guns in Georgia, More Bad Outcomes

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Firearm-related deaths are now the leading cause of death in U.S. children. The push to make guns more available is resulting in more tragic outcomes. In the U.S., putting too much mayonnaise on a sandwich can be a death sentence:

In Georgia, the law, signed by current governor Brian Kemp, allows Georgians to carry concealed handguns without first getting a license from the state. This law along with a previous “Guns Everywhere Law” has been associated with increased gun sales and increased gun violence and deaths.

After Uvalde, Amanda Gorman published the following poem

NY Times (5/27/22): Hymn For The Hurting

Everything hurts,
Our hearts shadowed and strange,
Minds made muddied and mute.
We carry tragedy, terrifying and true.
And yet none of it is new;
We knew it as home,
As horror,
As heritage.
Even our children
Cannot be children,
Cannot be.

Everything hurts.
It’s a hard time to be alive,
And even harder to stay that way.
We’re burdened to live out these days,
While at the same time, blessed to outlive them.

This alarm is how we know
We must be altered —
That we must differ or die,
That we must triumph or try.
Thus while hate cannot be terminated,
It can be transformed
Into a love that lets us live.

May we not just grieve, but give:
May we not just ache, but act;
May our signed right to bear arms
Never blind our sight from shared harm;
May we choose our children over chaos.
May another innocent never be lost.

Maybe everything hurts,
Our hearts shadowed & strange.
But only when everything hurts
May everything change.

Related blog posts:

IBD Updates: Probability of Needing a Stoma with Crohn’s Disease, “CEASE” anti-TNF study, Extending Tofacitinib Response Time

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AH Everhov et al. Inflamm Bowel Dis 2022; 28: 1160-1168. Open Access! Probability of Stoma in Incident Patients With Crohn’s Disease in Sweden 2003-2019: A Population-based Study

In a nationwide Swedish cohort of 18,815 incident patients with a minimum 5 years of follow-up, 652 (3.5%) underwent formation of a stoma. The 5-year cumulative incidence of stoma formation was 2.5%, with no differences between calendar periods  (2003–2006, 2007–2010, and 2011–2014).

RWM Pauweis et al. Clin Gastroentol Hepatol 2022; 20: 1671-1686. Open Access! Prediction of Relapse After Anti-Tumor Necrosis Factor Cessation in Crohn’s Disease: Individual Participant Data Meta-analysis of 1317 Patients From 14 Studies

C Ma. Clin Gastroentol Hepatol 2022; 20: 1668-1670. Associated editorial. Open Access! To Stop or Not to Stop? Predicting Relapse After Anti-TNF Cessation in Patients With Crohn’s Disease

This study captured data from 1317 patients (including 927 patients stopping infliximab and 390 patients stopping adalimumab) to develop risk prediction models.  “The authors confirm many of the high risk, albeit rather intuitive, factors that are associated with the risk of relapse, including younger age, younger age at diagnosis, smoking, upper gastrointestinal tract involvement, longer disease duration, absence of concomitant immunosuppressant use, previous anti-TNF failure, and absence of clinical remission.”

The editorial notes that even in the lowest risk group, more than 20% had risk of relapse within 1 year; in addition, stopping therapy increases risk of not recapturing remission with restart of treatment. “Stopping anti-TNF therapy is a highly personalized treatment decision and is one that carries considerable risks…therapeutic discontinuation of TNF antagonists should be reserved for the very small minority of patients who are in deep remission, have a strong desire to stop treatment, have no (or very few) characteristics of high-risk CD, can tolerate a substantial disease flare, and are fully informed of the risks of therapeutic withdrawal.”

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WJ Sandborn et al. Clin Gastroenterol Hepatol 2022; 20: 1821-1830. Open Access! Efficacy and Safety of Extended Induction With Tofacitinib for the Treatment of Ulcerative Colitis

Graphical abstract below shows that 52.2% of patients who did not achieve clinical response to 8 weeks’ treatment with tofacitinib 10 mg BID in the induction studies achieved a clinical response following extended induction (delayed responders). At Month 12 of OCTAVE Open, 70.3%, 56.8%, and 44.6% of delayed responders maintained clinical response and achieved endoscopic improvement and remission, respectively. Corresponding values at Month 36 were 56.1%, 52.0%, and 44.6%.

My take: By extending the treatment induction to 16 weeks to determine response (rather than 8 weeks), the authors showed that 75% of patients with ulcerative colitis in the initial cohort respond to tofacitinib.

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Eat More Chicken? (for EoE)

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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

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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.

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

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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.

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Knik Glacier Ice Field, AK