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, 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 15 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. I like to read, walk/hike, exercise, swim, and play tennis with my free time as well as go to baseball games. I do not have any financial relationships with pharmaceutical companies or other financial relationships to disclose. I have participated in industry-sponsored research studies.

Work Disability with Celiac Disease

Most patients that I see with celiac disease (CD) do very well after diagnosis/implementation of dietary therapy. A recent study indicates a subset of patients have significant work disability as adults.

SR Bozorg et al. Clin Gastroenterol Hepatol 2022; 20: 1068-1076. Open Access: Work Loss in Patients With Celiac Disease: A Population-based Longitudinal Study

In this large-scale nationwide study (part of the ESPRESSO study) from Sweden, the authors used prospectively recorded register data to estimate work loss in patients with CD in comparison to the general population, including the temporal relationship of work loss before and after diagnosis. This study included more than 16,000 patients with CD.

Key findings:

  • In 2015, patients with prevalent CD had a mean of 42.5 lost work days as compared with 28.6 in comparators
  • More than one-half of the work loss (60.1%) in patients with CD was derived from a small subgroup (7%), whereas 75.4% had no work loss
  • The annual mean difference between patients and comparators was 8.0 days of lost work 5 years before CD diagnosis, which grew to 13.7 days 5 years after diagnosis in the incident CD group (dx between 2008-2015)

In the discussion, the authors speculate about whether the work loss could be due to inadequate response to a gluten free diet; however, in this study, the authors found similar work loss between patients with CD with or without mucosal healing (only 25% underwent f/u biopsy).

My take: It would be interesting to see the pediatric corollary of work loss, namely school absenteeism and whether this is increased in a small subset as well. My suspicion is that the subset with increased work loss likely has a higher rate of functional disorders, in addition to CD, than the comparator group and probably accounts for a significant amount of the work disability.

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This sign works better at keeping people from wandering off the trail than “area under restoration.”

Delusional Thinking That COVID-19 Is Over

A couple recent articles indicate a lot of reasons for concern.

First of all, it is important to recognize that even among persons less than 55 years of age, COVID-19 was the leading cause of death in 2021. Inside Medicine: Open Access: The million US Covid dead are younger than you think.

Sadly, more than 300,000 deaths in the U.S. could have been averted (NPR: This is how many lives could have been saved with COVID vaccinations in each state)

There has been a culture shift to learn to live with the virus. This is evident almost everywhere from packed restaurants, crowded venues, etc. However, there is currently high transmission and variants that are evading vaccine protection as detailed by Eric Topol, Open Access: The Covid Capitulation

Key points:

  • The United States is now in the midst of a new wave related to Omicron variants BA.2 and BA.2.12.1 with over 90,000 confirmed new cases a day and a 20% increase in hospitalizations in the past 2 weeks…The real number of cases is likely at least 500,000 per day, far greater than any of the US prior waves except Omicron.
  • “Infections…beget more cases, …Long Covid, … sickness, hospitalizations and deaths. They are also the underpinning of new variants.”
  • CDC currently is vastly underestimating the number of cases leading many towards false confidence, “feeding the myth that the pandemic is over.”
  • “As of last week, 43% of new cases were attributable to BA.2.12.1 …. BA.2.12.1 is out-competing BA.2 with its 25% higher transmission rate, which foretells its further rise to dominance across the US in the days and weeks ahead.”
  • “This family of Omicron variants with functional impact indicates more rapid evolution of the virus than what we have seen previously.”
  • There has been a “reduction in vaccine effectiveness that we are now encountering…[Protection from severe disease] has declined to approximately 80%, particularly taking account the more rapid waning than previously seen.”
  • “It’s overly optimistic to think we’ll be done when Omicron variants run their course. Not only are they providing further seeding grounds for more variants of concern, but that path is further facilitated by tens of millions of immunocompromised people around the world, multiple and massive animal reservoirs, and increased frequency of recombinants.”
  • “Vaccinated individuals accounted for … 42 per cent [of the deaths] during the Omicron wave. This is attributable to waning of protection, lack of boosters, and the diminished protection against Omicron (BA.1).”
  • What needs to be done: More boosters/vaccines (“we rank 60th in the world’s countries for boosters”) along with more medicines, and nasal vaccines which could induce mucosal immunity

My take: Unfortunately, these articles indicate that we have a long way to go. High quality masks are going to be needed at health care settings for a while. For those trying to avoid COVID-19, it will remain important to avoid large indoor gatherings. For public policy/economic policy, we need to continue to fund COVID-19 resources.

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Here’s Why Therapeutic Drug Monitoring Should Work

RC Ungaro et al. Inflamm Bowel Dis 2022; 28: 649-651. Impact of Thiopurine Exposure on Immunogenicity to Infliximab Is Negligible in the Setting of Elevated Infliximab Concentrations

Background: Whether proactive therapeutic drug monitoring (pTDM) is superior to reactive TDM (rTDM) is not entirely clear, though some studies have shown better outcomes with pTDM. Additionally, Colombel et al (Clin Gastroenterol Hepatol 2019; 17: 1525-32) showed that antidrug antibodies during combination therapy were detected only in those with the lowest quartile of infliximab trough levels; this suggests that optimized monotherapy should be similarly effective to combination therapy.

Methods: The authors retrospectively analyzed a commercial laboratory database (Prometheus) with 3970 patients and paired 6-thioguanine (6-TGN) levels with infliximab (IFX) and antibodies to infliximab (ATIs)

Key findings:

  • “Those with higher levels of IFX had negligible benefit from concomitant thiopurine treatment in preventing ATIs.”
  • ATIs were detected in 9.9% of all patients. IFX level of >5 mcg/mL were associated with a very low risk of ATI (OR 0.05). “Immunogenicity was negligible (<3%) in the presence of IFX concentrations greater than 5 mcg/mL.”
  • 6-TGN levels (>125) were associated with lower risk of ATI, OR 0.42; though, this effect had a significant impact, only for those with with IFX <5 mcg/mL.
  • The authors note the prospective OPTIMIZE study (NCT04835506) should help determine the effectiveness of pTDM.

My take: In patients with IFX levels >5 mcg/mL, there does not appear to be much benefit for most patients from the addition of a thiopurine; this may not be true for those who are switching to a 2nd anti-TNF agent due to antidrug antibodies. This study supports pTDM to assure adequate IFX levels.

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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

White Sands National Park, New Mexico

Tweetorial: Refractory Gastroparesis

Tweetorial from “The Emoroid Digest”(posted 5/2/22):

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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.

Shifting of Infectious Diseases Due to Climate Change

CDC (January 2022): Open Access PDF: Our Risk of Infectious Diseases Is Increasing Because of Climate Change

“Between 2004 and 2018, the number of reported illnesses from mosquito, tick, and flea bites more than doubled, with more than 760,000 cases reported in the United States. Nine new germs spread by mosquitoes and ticks were discovered or introduced into the United States during this period. The geographic ranges where ticks spread Lyme disease, anaplasmosis, ehrlichiosis, and spotted fever rickettsiosis have expanded, and experts predict that tickborne diseases will continue to increase.”

EPA: Climate Change Indicators: Lyme Disease This EPA website has links to many other climate change indicators.

The lack of dots in Massachusetts in 2018 is due to a difference in
reporting standards, not an absence of Lyme disease

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AGA Expert Clinical Practice Update for Adults with GERD

R Yadiatpati et al. Clin Gastroenterol Hepatol 2022; 20: 984-994. AGA Clinical Practice Update on the Personalized Approach to the Evaluation and Management of GERD: Expert Review

The general approach, outlined in Figure 1, is to empirically treat patients with typical GERD symptoms for 4-8 weeks with single-dose PPI. In those with response, the goal is to use the lowest effective dose and consider reflux testing (“offer endoscopy with prolonged wireless reflux monitoring”) if needing prolonged treatment (>1 yr). In those without a response, adjusting treatment (possibly change medication or change to twice a day) should be considered and reflux testing (off treatment) is recommended as well in those lacking response to treatment.

Some of the recommendations/best practice advice:

  • Clinicians should provide standardized educational material on GERD mechanisms, weight management, lifestyle and dietary behaviors, relaxation strategies, and awareness about the brain-gut axis relationship to patients with reflux symptoms.
  • Clinicians should emphasize safety of proton pump inhibitors (PPIs) for the treatment of GERD.
  • Clinicians should provide patients presenting with troublesome heartburn, regurgitation, and/or non-cardiac chest pain without alarm symptoms a 4- to 8-week trial of single-dose PPI therapy. With inadequate response, dosing can be increased to twice a day or switched to a more effective acid suppressive agent once a day. When there is adequate response, PPI should be tapered to the lowest effective dose.
  • If troublesome heartburn, regurgitation, and/or non-cardiac chest pain do not respond adequately to a PPI trial or when alarm symptoms exist, clinicians should investigate with endoscopy and, in the absence of erosive reflux disease (Los Angeles B or greater) or long-segment (≥3 cm) Barrett’s esophagus, perform prolonged wireless pH monitoring off medication (96-hour preferred if available) to confirm and phenotype GERD or to rule out GERD.
  • Clinicians should perform upfront objective reflux testing off medication (rather than an empiric PPI trial) in patients with isolated extra-esophageal symptoms and suspicion for reflux etiology.
  • Clinicians should provide pharmacologic neuromodulation, and/or referral to a behavioral therapist for hypnotherapy, cognitive behavioral therapy, diaphragmatic breathing, and relaxation strategies in patients with functional heartburn or reflux disease associated with esophageal hypervigilance reflux hypersensitivity and/or behavioral disorders.
  • In patients with proven GERD, laparoscopic fundoplication and magnetic sphincter augmentation are effective surgical options, and transoral incisionless fundoplication is an effective endoscopic option in carefully selected patients.

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World’s Largest Pistachio (with my favorite pistachio eater). Alamogordo, New Mexico

America’s Formula Shortages –The Bigger Picture

A recent article (The Dispatch, Scott Lincicome: America’s Infant Formula Crisis and the ‘Resiliency’ Mirage) explains that the reasons we are facing formula shortages go beyond the Abbott recall.

Excerpts:

The infant formula crisis isn’t simply another case of a one-off event causing pandemic-related supply chain pressures to boil over. Instead, U.S. policy has exacerbated the nation’s infant formula problem by depressing potential supply….all part of our government’s longstanding subsidization and protection of the politically powerful U.S. dairy industry…

[Additionally, there] are strict FDA labeling and nutritional standards that any formula producer wishing to sell here must meet….These regulatory barriers are probably well-intentioned, but that doesn’t make them any less misguided—especially for places like Europe, Canada, or New Zealand that have large dairy industries and strict food regulations

The combination of trade and regulatory barriers to imported infant formula all but ensures that our almost $2 billion U.S. market is effectively captured by a few domestic producers—despite strong demand for foreign brands. What German company, for example, is willing to spend the time and money meeting all the FDA requirements—registration, clinical trials, labeling and nutritional standards, inspections, etc.—only to then face high import taxes that make its product uncompetitive except during emergencies? The answer: almost none…

Meanwhile, Abbott is in full-on crisis mode and has turned to flying in formula produced at an FDA-registered Irish affiliate…

WIC program’s use of sole supplier contracts has created a problem specific to the current crisis because … the big FDA recall just happened to hit the very producer—Abbott—holding most of the WIC contracts. 

My take: This article explains why there is not a simple switch to flip to fix the current formula bottlenecks.

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White Sands National Park, New Mexico

Antimicrobial Stewardship for Helicobacter Pylori

Yesterday, this blog discussed what is needed to achieve high cure rates for H pylori. One of my microbiology colleagues informed me that until recently there have only been susceptibility standards for clarithromycin from the Clinical Laboratory Standards.  Now, the European Committee on Antimicrobial Susceptibility Testing has criteria for clarithromycin, tetracycline, amoxicillin, levofloxacin, metronidazole, and rifampin. Given the difficulty culturing H pylori, his view is that stool testing is the most promising avenue for susceptibility testing because we now have the genes that determine resistance delineated for all of these drugs.

A related issue is antimicrobial stewardship: DY Graham. J-M Liou. Clin Gastroenterol Hepatol 2022; 20: 973-983. Open Access: Primer for Development of Guidelines for Helicobacter pylori Therapy Using Antimicrobial Stewardship

Key points:

  • “Therapies that fail to achieve at least a 90% cure rate should be abandoned as unacceptable”
  • “Antibiotics in the access group have lower resistance potential … They should be widely available and affordable. Amoxicillin, tetracycline, and metronidazole are classified as the access group. In contrast, clarithromycin and levofloxacin have higher resistance potential and are classified as the watch group. They should be prioritized as key targets of stewardship program and monitoring”
  • “Therapies that contain antibiotics which do not contribute to outcome should be eliminated”
  • The “full antisecretory activity of PPIs requires 3–4 days. This makes the actual duration of effective therapy shorter than the days it is administered…However, pharmaceutical companies often have chosen to shorten the recommended duration of therapy to obtain a marketing advantage at the expense of reduced effectiveness”
  • “Currently most H pylori infections receive empiric therapy, and the clinician does not know or even have access to treatment guidance based on local or regional antimicrobial susceptibility patterns…few hospitals or clinics offer susceptibility testing”
  • Even without susceptibility testing, clinicians could achieve much better results if test of cure data were carefully collected and analyzed
  • “Metronidazole-containing bismuth quadruple therapy is unique in that it appears that metronidazole resistance can be partially or completely overcome by increasing the dose and duration of therapy…metronidazole resistance as assessed in vitro does not correlate well with its effectiveness in vivo, especially when used as a component of a triple or quadruple therapy”

H pylori is difficult to eradicate:

  • Location: “the organisms reside within the highly acid stomach, which is physically outside of the body and thus poorly accessible to blood-borne antibiotics and the immune system”
  • Inoculum effect: “H pylori is also typically present in vast numbers, resulting in an inoculum effect … the inoculum effect is largely responsible for the failure of dual therapy with PPIs clarithromycin, metronidazole, or levofloxacin, as their effectiveness is undermined by emergence of resistance during therapy”
  • Biofilm and intracellular: “A proportion of H pylori attach to the surface of gastric cells, leading to a biofilm phenomenon, and some are present intracellular by requiring the use of antibiotics capable of penetrating into cells”
  • Dormant state: “H pylori can become dormant in part because they can replicate only when the pH is approximately 6…this results in a persister effect”

My take: The lack of action on H pylori susceptibility despite the current tools is a bad look for the GI community. Would this still be the case if the treatment were relegated to our infectious disease colleagues? Antibiotic stewardship is coming for H pylori -children and adults with this infection should have higher cure rates and easier treatment regimens.

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White Sands National Park, New Mexico

How To Achieve Helicobacter Pylori Cure Rates of >95%

Related to yesterday’s blog, here is an SNL commercial for the “Koohl” toilet (also with Benedict Cumberbatch) in 2016: SNL Koohl Toilet

————————————

DY Graham, SF Moss. Am J Gastroenterol 2022. 117: 524-528. Antimicrobial Susceptibility Testing for Helicobacter pylori Is Now Widely Available: When, How, Why

Key points:

  • Susceptibility testing for H pylori is widely available in the U.S. and should help optimize treatments to get success rates >95%. Testing is now available for the most common treatment antibiotics: amoxicillin, metronidazole, tetracycline, levofloxacin, clarithromycin, and rifabutin.
  • Handling/shipping specimens properly is important with susceptibility testing
  • The authors recommend a PPI which is minimally-affected by CYP2C19 metabolism, namely rabeprazole or esomeprazole.
  • Provide careful instructions to patient/family regarding treatment

Susceptibility Testing Labs (see Table 1):

A treatment algorithm is listed:

  • In the absence of highly effective empiric treatment or after treatment failure, the authors recommend susceptibility testing.
  • If clarithromycin susceptible, then a 14-day clarithromycin triple therapy course is recommended
  • If clarithromycin resistant but metronidazole susceptible, then 14-day metronidazole triple therapy
  • If resistant to both clarithromycin and metronidazole, then either a 14-day bismuth quadruple therapy, or a rifabutin triple therapy are preferred. However, if H pylori organisms are levofloxacin susceptible, then 14-day levofloxacin triple therapy may be a good option.
  • The authors recommend quinolone therapy only in the setting of susceptibility testing due to the FDA warnings about long-term adverse effects.

My take: Perhaps H pylori susceptibility testing availability needs to be a quality metric for hospitals and endoscopy centers.


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