Author Archives: gutsandgrowth

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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. During my fellowship, I had the opportunity to work with some of the most amazing pediatric gastroenterologists and mentors. Some of these individuals included Mitchell Cohen, William Balistreri, James Heubi, Jorge Bezerra, Colin Rudolph, John Bucuvalas, and Michael Farrell. I am grateful for their teaching and their friendship. During my training with their help, I received a nationwide award for the best research by a GI fellow. I have authored numerous publications/presentations including original research, case reports, review articles, and textbook chapters on various pediatric gastrointestinal problems. In addition, I have been recognized by Atlanta Magazine as a "Top Doctor" in my field multiple times. 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 North American Society for Pediatric Gastroenterology Hepatology and Nutrition (NASPGHAN), 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 17 terrific 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. Our group of physicians have worked closely together for many years. None of the physicians in our group have ever left to join other groups. I have also worked with the same nurse (Bernadette) since I moved to Atlanta in 1997. For many families, more practical matters about our office 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 to better the outcomes for children with inflammatory bowel disease – 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 helped enroll patients in industry-sponsored research studies.

Briefly noted: COVID-19 Cardiac Toxicity, U.S. Pandemic Research, Air-Bus Transmission

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VO Puntmann et al. JAMA Cardiol. Published online July 27, 2020. doi:10.1001/jamacardio.2020.3557. Full text: Outcomes of Cardiovascular Magnetic Resonance Imaging in Patients Recently Recovered From Coronavirus Disease 2019 (COVID-19)

Conclusion:  In this study of a cohort of German patients recently recovered from COVID-19 infection, CMR revealed cardiac involvement in 78 patients (78%) and ongoing myocardial inflammation in 60 patients (60%), independent of preexisting conditions, severity and overall course of the acute illness, and time from the original diagnosis. These findings indicate the need for ongoing investigation of the long-term cardiovascular consequences of COVID-19.

NY Times: E Emanuel et al.  Where Is America’s Groundbreaking Covid-19 Research? The U.S. could learn a lot from Britain.

Excerpt: “ Yet with over six million coronavirus cases and 183,000 deaths, the United States has produced little pathbreaking clinical research on treatments to reduce cases, hospitalizations and deaths. Even one of the most important U.S. studies to date, which showed that the antiviral drug remdesivir could reduce the time Covid-19 patients spent in the hospital to 11 days from about 15, had too few subjects to demonstrate a statistically significant reduction in mortality…[British] researchers found no benefits from the use of hydroxychloroquine in hospitalized Covid-19 patients, nor from the lopinavir-ritonavir drug combination. On the other hand, dexamethasone, an inexpensive steroid, was found to reduce mortality by up to one-third in hospitalized patients with severe respiratory complications.” 

“Unfortunately, unlike Britain, the United States has lacked a clear, unified message from government health care leaders, major insurance companies and hospital systems to put in place large, simple randomized trials that are considered the standard of care for Covid-19 treatment. We need to change that muddled approach now and reassert the nation’s clinical research excellence.”

NY Times: Roni Rabin. How a Bus Ride Turned Into a Coronavirus Superspreader Event

An excerpt: “A passenger on one of the buses had recently dined with friends from Hubei. She apparently did not know she carried the coronavirus. Within days, 23 fellow passengers on her bus were also found to be infected.

It did not matter how far a passenger sat from the infected individual on the bus, according to a study published in JAMA Internal Medicine on Tuesday. Even passengers in the very last row of the bus, seven rows behind the infected woman, caught the virus…

The new study “adds strong epidemiological evidence that the virus is transmitted through the air, because if it were not, we would only see cases close to the index patient — but we see it spread throughout the bus,” said Linsey Marr…

[THIS]  took place on Jan. 19, when there were still no confirmed Covid-19 cases reported in Ningbo…The potential for airborne transmission in close confined spaces raises concern about the winter months, when people will be spending more time indoors, Dr. Marr said. Her advice: “Avoid crowded indoor spaces where people are not wearing masks and the ventilation is poor.”

“Implementing psychological therapies for gastrointestinal disorders in pediatrics”

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Bonney Reed, Jessica Buzenski & Miranda A.L van Tilburg.  Expert Review of Gastroenterology & Hepatology (2020), DOI: 10.1080/17474124.2020.1806055 Full Text: Implementing psychological therapies for gastrointestinal disorders in pediatrics

This article is a useful and up-to-date review on the role of psychology to treat children with gastrointestinal disorders, particularly targeting functional GI disorders as well as children with inflammatory bowel disease. Also, I want to recognize Bonney and Jessica who have been so helpful for so many of our patients.

Areas covered:

  • Cognitive behavioral therapy (CBT)
  • Gut-directed hypnotherapy
  • Biofeedback-assisted relaxation training
  • E-treatment/telemedicine
  • Emerging therapies: Mindfulness, and Acceptance and Commitment therapy

Resources/Referrals:

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.

Proactive Therapeutic Drug Monitoring in Pediatric Crohn’s disease -Better Outcomes

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Y Gofin et al. Inflamm Bowel Dis 2020; 26: 1276-82.  Therapeutic Drug Monitoring Increases Drug Retention of Anti–Tumor Necrosis Factor Alpha Agents in Pediatric Patients With Crohn’s Disease

Retrospective study with 197 pediatric participants (2007-2018)

Key findings:

  • Compared with the TDM- group (n=98), the TDM+ group (n=99)
    • longer drug retention time (mean ± SE, 45.0 ± 2.7 vs 33.5 ± 2.4 months; P = 0.001)
    • lower hospitalization rate per patient per year (mean ± SE, 0.51 ± 0.7 vs 0.92 ± 0.81; P < 0.001)
    • higher treatment intensification rate (70% vs 18%; P < 0.001).
  • Analysis of the entire cohort showed a longer retention time for adalimumab vs infliximab (45.3 ± 2.8 vs 34.8 ± 2.5 months; P = 0.007)

My take: This is another study showing utility of proactive therapeutic drug monitoring

Related blog posts:

Which Crohn’s Disease Ulcerations Are Harder to Treat — Small Bowel or Colon?

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K Takenaka et al. Clin Gastroenterol Hepatol 2020; 18: 1545-1552. Small Bowel Healing Detected by Endoscopy in Patients With Crohn’s Disease After Treatment With Antibodies Against Tumor Necrosis Factor

Methods: This was a post-hoc analysis of data from a clinical trial from 116 patients with CD (46 with ileal and 70 with ileocolonic type) who received induction and then maintenance therapy with anti-TNF agents (2013-18). Median age 29 years.

Key findings (based on findings from balloon-assisted enteroscopy )

  • Before treatment, small bowel ulcerations were present in 114 patients (98%); 42 patients (60%) with ileocolonic disease had colon ulcerations.
  • During maintenance therapy, 41/114 patients (36%) had small bowel endoscopic healing; all the patients with small bowel endoscopic healing also had colonic endoscopic healing.
  • Failure to achieve small bowel endoscopic healing was significantly associated with stricturing or penetrating disease (P = .014), lack of concomitant treatment with immunomodulators (P = .015), and having received previous treatment with an anti-TNF agents (P = .018).
  • The authors found that endoscopic healing was only 35% (36% for small bowel and 79% for colonic inflammation)

My take: Small bowel inflammation did not respond to treatment as well as colonic inflammation.  The implication of this study is that even in patients who are doing well clinically with treatment, disease progression especially in the small bowel may be ongoing.

Briefly noted: M Kayal et al. Inflamm Bowel Dis 2020; 26: 1079-1086.  Inflammatory Pouch Conditions Are Common After Ileal Pouch Anal Anastomosis in Ulcerative Colitis Patients.

  • In this retrospective study of adults with ulcerative colitis who had undergone total proctocolectomy (TPC) with ileal pouch anal anastomosis (IPAA). Acute pouchitis occurred in 205 patients (53%), 60 of whom (30%) progressed to chronic pouchitis.
  • Cuffitis and Crohn’s disease-like condition (CDLC) of the pouch occurred in 119 (30%) patients and 46 (12%) patients
  • Pouch failure was noted in 6.7%
  • Only one-third of patients with chronic pouchitiis, cuffitis and CDLC responded to biologic therapy

Related blog posts:

Does Clostridium difficile Increase the Risk of Surgical Resection in Pediatric Crohn’s Disease?

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A recent retrospective & prospective study (J Hellmann et al. Inflamm Bowel Dis 2020; 26: 1212-21. Microbial Shifts and Shorter Time to Bowel Resection Surgery Associated with C. difficile in Pediatric Crohn’s Disease. Associated editorial 1222-3) suggests that C difficile infection (CDI) is associated with an increased risk of bowel resection surgery.

In the retrospective arm with 75 pediatric patients (<22 years): Key findings:

  • 14 of 75 had positive C difficile testing (mainly PCR, especially after 2009).
  • The rate of bowel resection surgery increased from 21% in those without C. difficile to 67% in those with (P = 0.003).
  • From a Kaplan-Meier survival model, the hazard ratio for time to first surgery was 4.4 (95% CI, 1.2–16.2; P = 0.00) in patients with positive C. difficile testing in the first year after diagnosis.

Importantly, the study was unable to distinguish between C difficile colonization versus infection.

In the prospective arm with 70 patients, patients underwent meatgenomic sequencing. Those with a positive PCR assay (irregardless of symptoms or calprotectin) were considered to have CDI.

  • 10 of 70 (14%) tested positive for CDI
  • 40% of those with CD and positive CDI had a history of surgery vs 15% with negative C difficile testing
  • Fecal calprotectin levels were elevated (>250) in 40% of both those testing positive for CDI and those testing negative
  • The overall fecal microbiome composition was not statistically significantly different between CDI-positive and CDI-negative
  • There were significant differences in the fecal microbiome composition between those with prior surgery and those without prior surgery.  Depletion of Alistipes and Ruminococcus species and reduction in methionine biosynthesis were noted in patients with both C. difficile carriage and past surgery

My takes:

  1. Based on my reading, the authors assert an association of shorter time to surgery associated with CDI in the retrospective cohort.  Because testing for CDI is common in those with flare-ups, it is unclear if this is a temporal phenomenon or is a causal relationship.
  2. It is interesting that their prospective cohort did not have an increased calprotectin level in those with CDI-positivity or overall composition change in microbiome in the CDI-positive group.  It would be of interest if these studies were confined to those with cytotoxin-assay positivity which has been shown to correlate with clinical outcomes.  In previous studies, individuals with PCR-positive CDI & cytotoxin-assay negative had similar outcomes to those with negative PCR assays.

Related blog posts:

COVID-19 -New Infection Fatality Data & How to Fix the Testing Mess

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From Annals of Internal Medicine 2020 https://doi.org/10.7326/M20-5352: J Blackburn et al. Full Text: Infection Fatality Ratios for COVID-19 Among Noninstitutionalized Persons 12 and Older: Results of a Random-Sample Prevalence Study

Background: Mortality rates have been calculated from confirmed cases, which overestimates the infection fatality ratio (IFR). To calculate a true IFR, population prevalence data are needed from large geographic areas where reliable death data also exist.

Results: The Table below suggests IFR of 0.01% for those <40, 0.12% for those 40-59, and 1.71% for those ≥60 in noninstitutionalized persons.  The Table indicates nearly a 3-fold increase risk in Non-White persons. Whites had an IFR of 0.18%; non-Whites had an IFR of 0.59%. Also, I think the Table incorrectly suggests that Females have a higher IFR than Males (but the numbers suggest that they are equivalent).

From The New Yorker, Atul Gawande: We Can Solve the Coronavirus-Test Mess Now—If We Want To

This is a lengthy article which describes some of the mistakes that we’ve made with testing, some of the technical details with various tests, pooled testing, at-home testing, wastewater testing, and how to fix testing (including assurance testing) to gain control of this pandemic.

An excerpt:

We could have the testing capacity we need within weeks. The reason we don’t is not simply that our national leadership is unfit but also that our health-care system is dysfunctional….

In the United States, getting a test is anything but easy…[And] through early August, results routinely took four days or more, making the tests essentially useless. 

“Assurance testing” has been required by countries such as Iceland, France, and Germany for travellers from abroad in order to avoid a mandatory two-week quarantine

Intestinal Barrier Function and Risk of Crohn’s Disease

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Several recent studies have examined biomarkers to predict Crohn’s disease.  A recent prospective study (W Turpin et al. Gastroenterol 2020; DOI: https://doi.org/10.1053/j.gastro.2020.08.005. Increased Intestinal Permeability is Associated with Later Development of Crohn’s Disease) sought to determine whether increased intestinal permeability, as measured by urinary fractional excretion of lactulose to mannitol ratio (LMR), is associated with future development of CD.

Methods: 1420 asymptomatic first-degree relatives (6–35 years old) of patients with CD (collected from 2008 through 2015) had LMR measured and were then followed for a diagnosis of CD from 2008 to 2017, with a median follow up time of 7.8 years. We analyzed data from 50 participants who developed CD after a median of 2.7 years during the study period, along with 1370 individuals who remained asymptomatic until October 2017

Key findings:

  • An abnormal LMR (> 0.03) was associated with diagnosis of CD during the follow-up period (hazard ratio, 3.03; 95% CI, 1.64–5.63; P=3.97×10 -4).
  • This association remained significant even when the test was performed more than 3 years before the diagnosis of CD (hazard ratio, 1.62, 95% CI, 1.051–2.50; P=.029).

My take:  It remains unclear whether abnormal barrier function primarily precedes or follows CD development.  The authors state that these findings support a model in which altered intestinal barrier function contributes to pathogenesis.

Yellow or Blue for Cautery of Non-pedunculated Polyps

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Almost all polyps that pediatric gastroenterologist manage are pedunculated polyps.  Nevertheless, a recent study (H Pohl et al. Gastroenterol 2020; 159: 119-28. Full text: Effects of Blended (Yellow) vs Forced Coagulation (Blue) Currents on Adverse Events, Complete Resection, or Polyp Recurrence After Polypectomy in a Large Randomized Trial) on cautery for non-pedunculated polyps was intriguing.

Methods: This multicenter, randomized, controlled, single-blinded study enrolled patients with a large colorectal polyp across 18 medical centers between April 2013 and October 2017. N=928.  ERBE device.

Key finding:

  • Equivalent results were noted with both blended current (Yellow) or forced coagulation (Blue)
    • “Serious adverse events occurred in 7.2% of patients in the Endocut (blended) group and 7.9% of patients in the forced coagulation group, with no significant differences in the occurrence of types of events.”
    • Proportions of polyps that were completely removed: 96% in the Endocut group vs 95% in the forced coagulation group
    • Proportion of polyps found to have recurred at surveillance colonoscopy: 17% for both groups
    • “Endocut more frequently caused intraprocedural bleeding that required treatment than forced coagulation (17% vs 11%). In contrast, small residual tissue islands were more frequently described in the forced coagulation group than in the Endocut group.”

Discussion: 

  • “We also did not include pedunculated polyps. Because these polyps have a greater risk of immediate bleeding, we may infer from our study that it may be safer to apply a coagulation current with a lower risk of immediate bleeding to these polyps.”

My take: Both of these settings yielded similar results.  For now, with pedunculated polyps, probably best to rely on the coagulation setting (Blue).

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

Eric Topol to Stephen Hahn/FDA: “Tell the Truth or Resign”

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An open letter from Eric Topol to Dr.Stephen Hahn details a number of glaring mistakes at the FDA which threaten its credibility and its mission.

Here’s the link: Dear Commissioner Hahn: Tell the Truth or Resign

The letter points to three high profile, politically-fraught decisions at the FDA:

  1. Authorization of hydroxychloroquine
    • “Immediately after President Trump widely and aggressively promoted hydroxychloroquine as a “miracle drug,” on March 30, 2020, you granted an Emergency Use Authorization (EUA) for this drug without any sufficient or meaningful supportive evidence”
  2. Authorization of convalescent plasma
    • “This is a major advance…[A]nd a 35% improvement in survival is a pretty substantial clinical benefit. What that means is — and if the data continue to pan out — [of] 100 people who are sick with COVID-19, 35 would have been saved because of the admission of plasma.” Every part of that statement is incorrect and a blatant misrepresentation of the data. “
  3. Authorizaton of remdesevir
    • The third breach of evidence-based data was your EUA issued August 28, 2020 broadening the remdesivir approval to include any patient hospitalized with moderate COVID-19. There are insufficient data to support this approval, as it is based on small, open-label studies with subjective endpoints.

Dr. Topol worries that Dr. Hahn will further erode confidence in the FDA by approval of a SARS-CoV-2 vaccine prematurely.  “Any shortcuts will not only jeopardize the vaccine programs but betray the public trust, which is already fragile about vaccines, and has been made more so by your lack of autonomy from the Trump administration and its overt politicization of the FDA.”

More Data on Magnetic Sphincter Augmentation for Gastroesophageal Reflux

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In adults with gastroesophageal reflux, there is more data that magnetic sphincter augmentation (MSA) is a good option for many.  R Bell et al. Clin Gastroenterol Hepatol 2020; 18: 1736-1743. Full Text: Magnetic Sphincter Augmentation Superior to Proton Pump Inhibitors for Regurgitation in a 1-Year Randomized Trial)

Methods: Patients with moderate to severe regurgitation (assessed by the foregut symptom questionnaire) despite once-daily PPI therapy (n = 152) were randomly assigned to groups given twice-daily PPIs (n = 102) or laparoscopic MSA (n = 50) at 20 sites.

Key findings:

  • MSA resulted in control of regurgitation in 72/75 patients (96%); regurgitation control was independent of preoperative response to PPIs. It is noted that none of the patients in this study had grade C or grade D esophagitis.
  • Only 8/43 patients receiving PPIs (19%) reported control of regurgitation.
  • In the MSA group, MSA, 61 (81%) had improvements in GERD health-related quality of life improvement scores (greater than 50%) and 68 patients (91%) discontinued daily PPI use. The Demeester scores improved from 33.4 to 3.5 at 6 months post implanation
  • Esophageal acid exposure time decreased from 10.7% to 1.3% (P < .001) from study entry to 1-year after MSA.
  • Safety: No serious perioperative adverse events occurred in any arm of the study. Although 19 (39.6%) MSA patients and 10 (33.3%) MSA crossover patients reported instances of dysphagia, MSA patients reported less dysphagia at 6 and 12 months than at baseline

Discussion points from authors:

  • Relatively limited duration of follow-up, though “other studies of MSA have documented little decrease in efficacy between 1 and 5 years of follow-up”
  • The American College of Gastroenterology guidelines indicate “that surgical therapy is not recommended for patients who do not respond to PPI therapy. However, the basis for these recommendations and the types of symptoms evaluated for response to PPI therapy is unclear. Three prospective cohort studies have compared the effectiveness of laparoscopic fundoplication between PPI responsive and  nonresponsive populations and found significant symptom improvement with laparoscopic fundoplication in PPI nonresponders, though not quite as much as in PPI responders”
  • Increased bloating which is common after laparoscopic fundoplication was not evident with MSA which found a decrease from baseline.  “. Continued ability to belch was reported in 99% (n = 74 of 75) of all patients who received MSA at 12 months.”

In the associated editorial, JE Richter (Clin Gastroenterol Hepatol 2020; 18: 1685-1687 Full text: Laparoscopic Magnetic Sphincter Augmentation: Potential Applications and Safety Are Becoming More Clear—But the Story Is Not Over) notes that “erosion and migration of the MSA device have been a rare event thus far. In a total of nearly 10,000 device placements, there were 29 reported cases of erosions…Smaller devices were associated with higher rates of erosions. The 12-bead device was responsible for 18 of 29 erosions (62%) and is no longer available for implantation…To an admitted skeptic about new antireflux treatments, the available data about the symptomatic and
physiological effectiveness, durability, and safety of MSA are very impressive. I believe this procedure now deserves to be routinely done as an alternative surgical procedure to traditional fundoplication for patients with mild-moderate GERD….patients with severe GERD and structural sphincter dysfunction still need the traditional fundoplication”

My take: This study and others shows that MSA (aka Linx) is an effective treatment option for many adult patients with medically-refractory regurgitative reflux.

Related blog posts:

It is surprising to me that almost half of the U.S. thnk that we have handled the pandemic well