Thank You Larry

One of the difficult aspects at this point in my career is saying goodbye as physicians retire.  Larry Saripkin, who is an amazing person, is retiring (last day yesterday). 

I first met Larry when I was working at Egleston Hospital. Larry, along with Jeff Lewis, provided coverage for me when I had become the single physician in my group.  This allowed me to be off when our youngest son was born.  Then, later, Larry helped convince me to join the merging GI groups at Scottish Rite (23 years ago).  This has been one of my best decisions.  Of course, I feel that our group delivers very good care for our patients.  Yet, the main reason why it has been a good choice is working alongside some terrific individuals. 

Larry has a keen intellect and a wonderful ability to connect with everyone, even families with very stressful medical conditions. He is very generous with his time.  I remember one night when he was on-call, the parents of one of my patients called. They were upset because they could not get the feeding pump to work.  They told me that Larry insisted on driving out to their house (around 11 pm).  He and his wife showed the family how to work the pump.

For about 15 years, he has spent a week every summer at Camp Oasis as the medical director.  At heart, Larry is still a kid.  For years, he would take some of the younger staff (or kids of other physicians) with him when he went to Bonaroo.

He has served as a mentor to many of us in our group and to about a dozen scribes who have moved on to become physician assistants or to medical school/physicians.

Countless families have told me how important Larry has been to them. He has attended many of his patients’ celebrations (eg. weddings).

It will be bittersweet going forward when I walk by Larry’s office & missing out on some great story or some new music.

In this picture with Melissa and Cassie (from 2011), Larry is dressed up
as a cheeseburger (with a fake mustache) at Camp Oasis.

Autoimmune Hepatitis: Safety of Low Dose Steroids and Utility of Aminotransferases

K Manwani et al. JPGN 2022; 75: 252-256. Long-Term Growth in Children and Young People with Autoimmune Liver Disease Treated with Daily Steroids

This retrospective study of patients (n=74) diagnosed with autoimmune hepatitis (AH) prior to 16 years of age examined the safety of low dose steroids. Median age of patients with 12.8 yrs and median followup was 12.6 years. Typically, after induction, patients were tapered over ~2 months to 5 mg per day (& 2.5 mg per day if <12 years). Key findings:

  • Growth of patients with AILD on a daily maintenance dose of steroids remains stable and within normal range during long-term follow up.  At all time-points, the mean z-scores for weight, height and BMI were within the normal range, indicating normal nutritional status. 
  • Small, daily doses are effective in maintaining disease control and minimize the need for high-dose steroid pulses during relapses.
  • In this cohort, there were 14 patients in which prednisolone was utilized as monotherapy; the majority received cotherapy with azathioprine (n=44), mycophenolate (n=12); triple-therapy was utilized tacrolimus (n=4).
  • Prednisolone was stopped in 17 patients (23%) after a median time of 9.5 years (range 3 years-14 years)

M Biewenga et al. Clin Gastroenterol Hepatol 2022; 20: 1776-1783. Open access! Aminotransferases During Treatment Predict Long-Term Survival in Patients With Autoimmune Hepatitis Type 1: A Landmark Analysis

In this multicenter cohort study (n=301), it was shown that higher aminotransferases during treatment were independent of baseline risk factors associated with liver transplantation–free survival in patients with AIH type 1. Median followup was 99 months. Key finding:

  • During follow-up, 15 patients required liver transplantation and 33 patients died
  • In multivariate analysis AST at 12 months (HR, 2.13; P < .001) was predictive for survival independent of age, AST at diagnosis and cirrhosis, while IgG was not associated with survival (HR, 1.30; P = .53)
  • There was a trend toward a worse survival in patients with mildly elevated aminotransferases (1–1.5× upper limit of normal) compared with patients with normal aminotransferases (P = .097)

My take: Normalization of AST (aminotransferases), especially during the first year of treatment, is associated with better long-term outcomes. The study by Manwani et al suggest that long-term low dose steroids are associated with low risks.

Also: Y Li et al.Hepatology 2022; 76: 564-575. Genome-wide meta-analysis identifies susceptibility loci for autoimmune hepatitis type 1 This study with 1622 Chinese patients identified two novel loci (CD28/CTLA4/ICOS and SYNPR) and may provide potential targets for additional treatments.

Related blog posts:

AST Values and Cumulative Live Transplant-Free Survival

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

It’s Still Not Needed: Pre-op COVID Testing Prior to Endoscopy

Last year, the AGA stated that pre-endoscopy COVID testing is not needed:

This has turned out to be good advice:

A Hann et al. Gut 2022; http://dx.doi.org/10.1136/gutjnl-2022-327053. Open Access! Impact of pre-procedural testing on SARS-CoV-2 transmission to endoscopy staff

In this retrospective study, “during a 20-month period until December 2021 using PPE and three different test approaches: no testing (n=4543), rapid antigen (RA) testing (n=682) and RT-PCR testing (n=10 465). In addition, 60 endoscopies were performed in patients with proven COVID-19. Not a single staff member became infected with SARS-CoV-2 during the 20 months analysed; vaccination rate of the team was 97%.”

The authors note that routine testing of clinical team was not performed; thus, they cannot exclude the possibility of asymptomatic infections.

My take (borrowed in part from authors): “PPE is highly effective for avoidance of SARS-CoV-2 transmission during upper or lower GI endoscopies.” Pre-op testing for COVID has many downsides: increased costs, delays in care, potential exacerbation of health disparities, and detrimental effects to endoscopy efficiency (especially with inconclusive results)

Knik River Glacier, AK

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 .

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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?

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).

More Guns in Georgia, More Bad Outcomes

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

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.”

Related blog posts:

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.

Related blog posts: