Author Archives: gutsandgrowth

Unknown's avatar

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.

Why CDC is Drafting New Guidelines for Screening Children for Perinatally-Acquired Hepatitis C Infection

Posted on by

EW Hall et al. J Pediatr 2023; 258: 113409. Open Access PDF! Cost-Effectiveness of Strategies to Identify Children with Perinatally Acquired Hepatitis C Infection

In this study, the authors modeled three strategies for screening for Hepatitis C infection in children and compared to baseline testing (current approach): : anti-HCV with reflex to HCV RNA at 18 months among children known to be perinatally exposed.

New strategies:

  • #1: HCV RNA testing at 2-6 months among infants known to be perinatally exposed
  • #2 universal anti-HCV with reflex to HCV RNA at 18 months among all children
  • #3 universal HCV RNA testing at 2-6 months among all infants

Key findings:

  • Each of the 3 alternative testing strategies resulted in an increased number of children tested and improved health outcomes. HCV RNA testing at 2-6 months (test strategy 1) was cost-saving and resulted in a population-level difference in cost of $469 671.
  • More testing in each of the universal comparison strategies resulted in increased QALYs, but also over $38 million to over $129 million

In the discussion, the authors elaborate on why testing at 2-6 months is now the best approach:

  • “Factors driving these results include pediatric loss to follow up at older ages, high attendance at well-child visits in the first 6 months of life, and highly sensitive nucleic acid testing with reliable results starting at age 2 months.”
  • “One study assessing >150 000 children at 2 health networks spanning 20 states determined children rarely missed 2-month, 4-month, and 6-month well-care visits, whereas 15-month and 18-month visits were attended by less than one-half of publicly insured children”
  • Current recommendations are for all pregnant women receive HCV screening, though currently it is below 50%. The universal testing strategy becomes more cost prohibitive as more women receive HCV testing in pregnancy

The CDC has undertaken a review and is likely to implement the 2-6 month old testing strategy as a recommendation. The authors of this study are involved in this process. A slide set reviewing the draft recommendations from 12/6/22:

Link 40 Slides: Overview of draft CDC recommendations for perinatal hepatitis C testing

Some selected slides:

My take (borrowed from authors): Testing of perinatally exposed infants at age 2-6 months with a single HCV RNA test will reduce costs and improve health outcomes.

Related blog posts:

Does a Liver Transplantation Improve the Course of Inflammatory Bowel Disease?

Posted on by

AR Safarpour et al. Inflamm Bowel Dis 2023; 29: 973-985. Alterations in the Course of Inflammatory Bowel Disease Following Liver Transplantation: A Systematic Review and Meta-analysis

The authors identifed 25 studies which met inclusion criteria. Key findings:

  • In the analysis of studies with 3-category outcomes (n = 13), the pooled frequencies of patients (n=646) with improved, unchanged, or aggravated IBD course after LT were 29.4%, 51.4% (, and 25.2%.
  • Subgroup analyses revealed that patients with ulcerative colitis (UC), younger age at LT, or shorter duration of follow-up were more likely to have an improved disease course.
  • In the analysis of studies with 2-category outcomes (n = 12), the pooled frequencies of patients (n=672) with improved/unchanged or aggravated IBD course were 73.6% and 24.1%, respectively

My take: Despite the intensification of immunosuppression, most often the course of IBD is unchanged in patients following a liver transplantation.

Related blog posts:

View from L’Jaardin Exotique in Eze, France

Why Didn’t Screening for Biliary Atresia Improve Outcome In This Study?

Posted on by

ZJ Kastenberg et al J Pediatr 2023; 257: 113339. Fractionated Bilirubin Among 252 892 Utah Newborns with and Without Biliary Atresia: A 15-year Historical Birth Cohort Study

This retrospective study (2005-2019) used an administrative data from a large integrated healthcare network in Utah to identify newborns with abnormal fractionated bilirubins. since 2005, all newborns at this healthcare system had a fractionated bilirubin measured.

Key findings:

  • There were 252 892 newborns with fractionated bilirubin assessed, including 26 of those subsequently confirmed to have biliary atresia (BA).
  • Conjugated or direct bilirubin was elevated in all 26 infants with BA and an additional 3246 newborns (1.3%) without BA. The lowest direct bilirubin in the BA group was 0.6, just above cutoff value of 0.5 mg/dL. The conjugated bilirubin cutoff value wa 0.2 mg/dL.
  • The 15-year crude birth prevalence of BA was 0.68 per 10,000 births in this cohort
  • Median time to Kasai HPE was 69.5 days

This study found that all infants with BA have elevated conjugated or direct bilirubin at birth. The authors estimate that a healthcare system with about 30,000 deliveries per year, would have between 450 and 630 newborns that would require a second screen. In this group, 96 per 100,000 screened newborns (~1 in 1000) will have a positive second screen at 2-week well check and need further evaluation.

What I don’t understand about this paper is how the authors omit a discussion of the age of Kasai HPE. How is it that all of these newborns received a fractionated bilirubin and the age of Kasai HPE is not improved compared to other U.S locations that have not implemented universal testing? (Previous data from 15 ChiLDReN sites indicate age of Kasai HPE 65-70 days and unchanged over past 30 years, see blog post: Online Aspen Webinar (Part 5) -Biliary Atresia Diagnosis and Screening).

The authors note that implementation of screening could be improved with newer tests (eg. MMP-7) but that more analysis is needed to determine if screening is cost-effective and avoids harm (eg. subjecting healthy newborns to invasive testing).

My take: If universal screening is implemented, it is imperative to show that it helps and to set up the needed infrastructure to arrange appropriate followup. The first surrogate marker of this effort would be improving the age of surgical intervention.

As an aside, I find the new page numbering by The Journal of Pediatrics to be quite annoying. When you are going through the hard copy of the Journal, it is more difficult to find the articles that are listed in the table of contents because the articles are not ordered by lowest to highest numbered page. Each article is given a single page number like 113339 in this article but inside the article it is numbered page 1–10 (or however long the pages). The article prior could be a lower or higher page number. Until hard copies are eliminated, it would be an improvement if the articles could at least be ordered such that the next article would not have a lower page reference than the preceding article.

Related blog posts:

Castle Hill Park, Nice France

Be Careful with Biliary Atresia Diagnostic Biomarkers

Posted on by

B Aleiri et al. JPGN 2023; 77: 97-102. Matrix Metalloproteinase-7 and Osteopontin Serum Levels as Biomarkers for Biliary Atresia

In this study, serum was assessed from 32 biliary atresia (BA) patients and 27 controls.

Key findings:

  • Median MMP-7 was higher in BA (96.4 vs 35 ng/mL; P < 0.0001) with an optimal cut-off value of 69 ng/mL. Sensitivity and specificity was 68% and 93%, respectively [negative predictive value (NPV) = 71%]
  • Median osteopontin (OPN) was higher in BA (1952 vs 1457 ng/mL; P = 0.0001) and an optimal cut-off of 1611 ng/mL. Sensitivity and specificity was 84% and 78%, respectively (NPV = 81%)

The authors note that numerous studies from Asian countries have shown very high sensitivity and specificity for MMP-7. These studies used different cut-offs based on the testing kit. One limitation of this study was that samples were stored for a median of 12 years and perhaps this affected the results (some prior studies also used banked specimens).

My take: When these levels are very elevated, they are highly suggestive of BA. This study serves as a caution to note that the sensitivity at typical cut off values could be suboptimal

Related blog posts:

Le Jardin Exotique in Eze, France

Prevalence of Elevated ALT in U.S. Adolescents

Posted on by

AK Mischel et al. JPGN 2023; 77: 103-109. Prevalence of Elevated ALT in Adolescents in the US 2011–2018

Using NHANES data for 12-19 year olds, the authors examined rates of elevated ALT. Elevated ALT was defined as >22 U/L (females) and >26 U/L (males)  Key findings:

  • Prevalence of elevated ALT in adolescents was 16.5% overall and 39.5% among those with obesity
  • For White (W), Hispanic (H), and Asian (A) adolescents, prevalence of elevated ALT was 15.8%, 21.8%, and 16.5% overall. In overweight adolescents, 12.8% (W), 17.7% (H), and 27.0% (A), and in those with obesity, 43.0% (W), 43.5% (H), and 43.1% (A) in those with obesity, respectively
  • Prevalence was much lower in Black adolescents (10.7% overall, 8.4% for overweight, 20.7% for obesity)
  • Prevalence of ALT at 2X-ULN was 6.6% in adolescents with obesity
  • Hispanic ethnicity, age, male sex, and higher BMI were independent predictors of elevated ALT

My take: It is hard to get very excited about a mildly elevated ALT value when 1 in 6 adolescents has this as well as ~40% of adolescents with obesity.

Related blog posts:

Bougainvillea in Eze, France
View from Cap d’Ail Trail (near Eze, France)

Only 30% Ready for Transition from Pediatric IBD to Adult Practice

Posted on by

A Foster et al. J Pediatr 2023; 258: 113403. Transition Readiness in Youth with Inflammatory Bowel Disease

In this cross-sectional multicenter study evaluating transition readiness in individuals (n=186, prospectively recruited ) with IBD 16-19 years old, the authors used the validated ON Taking Responsibility for Adolescent to Adult Care (ON TRAC) questionnaire. 

Key findings:

  • ON TRAC scores determined that 26.6% of AYAs at pediatric and 40.4% at adult centers reached the threshold of readiness. The findings are limited by potential nonresponse & sampling bias.
  • Disease remission negatively (P = .03) associated with ON TRAC scores.
  • A significant percentage of AYAs reported moderate-to-severe depression (21.7%) and generalized anxiety (36%); however, neither were significantly associated with ON TRAC scores

The authors suggest that a joint clinic with adult/pediatric providers may be helpful to improve transition.

MB Cohen. J Pediatr 2023; 258. DOI:https://doi.org/10.1016/j.jpeds.2023.113556 Are You Ready to Transition? In commentary on this article, Dr. Cohen writes the following: “a novel finding was that transition readiness was inversely related to disease remission; this confirms what had been previously suggested.1 Patients who are doing well may not be as engaged in developing skills for transition readiness and knowledge about their chronic illness, unlike those with more significant disease or symptoms.”

My take: Many studies show that adolescents and young adults with IBD are not fully prepared to transition to adult medical practices. In my view, it would be better to encourage the young adult to continue engaging with his/her parents until readiness is achieved rather than try to change to a multispecialty clinic.

Related blog posts:

Castle Hill Park, Nice France

Infliximab Injections Coming Soon

Posted on by
  1. L Gianolio et al JPGN 2023; 77(2):p 235-239, August 2023. Effectiveness of Switching to Subcutaneous Infliximab in Pediatric Inflammatory Bowel Disease Patients on Intravenous Maintenance Therapy

Key findings: After switching from IV infliximab to SC 120 mg every other week, 6 of 7 patients remained in clinical remission with no significant changes in laboratory markers and median infliximab trough levels (12.3 µg/mL at baseline; 13.9 and 14.0 µg/mL at 6 and 40 weeks respectively). 

2. Gastroenterology & Endoscopy News (7/31/23) Safety, Efficacy of Subcutaneous Infliximab Supported by Trial

Excerpt:

In this multinational trial, called LIBERTY-CD, the median trough level was 16 mcg/mL, which is higher than that typically associated with IV dosing, according to Dr. Hanauer, who presented the results at Digestive Disease Week 2023 (abstract 1028)… “most professional societies to recommend a trough of 10 mcg/mL,” Dr. Hanauer said….

All patients received induction doses of infliximab by IV at weeks 0, 2 and 6. Those who achieved at least a 100-point reduction in the Crohn’s Disease Activity Index (CDAI), which accounted for 86% of the 396 patients initially enrolled, were randomized in a 2:1 ratio to receive 120 mg of subcutaneous infliximab (CT-P13) or placebo every two weeks.

The proportion of patients meeting the end point of clinical remission, defined on the basis of CDAI, was 62.3% for active therapy and 32.1% for placebo (P<0.0001). The proportion of patients in the active treatment arm achieving an endoscopic response was nearly three times higher than the proportion in the placebo arm (51.1% vs. 17.9%; P<0.0001).

My take: This study shows that SC infliximab (after IV induction) should be effective. A study showing that the SC product is not inferior to the IV dosing would be helpful. It is likely that vedolizumab will receive approval in U.S. for a similar IV induction followed by maintenance subcutaneous therapy in the next year.

Eze, France

High Rates of Denying Medical Care for Medicaid Patients Managed by Health Insurers

Posted on by

7/19/23 NY Times: Insurers Deny Medical Care for the Poor at High Rates, Report Says

Some excerpts:

Private health insurance companies paid by Medicaid denied millions of requests for care for low-income Americans with little oversight from federal and state authorities, according to a new report by U.S. investigators published Wednesday.

Medicaid, the federal-state health insurance program for the poor that covers nearly 87 million people, contracts with companies to reimburse hospitals and doctors for treatment and to manage an individual’s medical care. About three-quarters of people enrolled in Medicaid receive health services through private companies, which are typically paid a fixed amount per patient rather than for each procedure or visit.

The report by the inspector general’s office of the U.S. Department of Health and Human Services details how often private insurance plans refused to approve treatment and how states handled the denials.

Doctors and hospitals have increasingly complained about what they consider to be endless paperwork and unjustified refusals of care by the insurers when they fail to authorize costly procedures or medicines…The investigators also raised concerns about the payment structure that provides lump sums per patient. They worried it would encourage some insurers to maximize their profits by denying medical care and access to services for the poor...

The investigators emphasized the insurers were much more aggressive in refusing to authorize care under Medicaid than under Medicare…Unlike with Medicare, if an insurer refuses to authorize a treatment, patients are not automatically provided with an outside medical opinion as part of their appeal...

The investigators also found that state oversight of coverage denials was lax. Many states do not routinely examine the insurers’ denials nor collect information about how many times a plan denies requests for prior authorization...

The denial rates recorded by the investigators varied widely by insurer and by state.

My take: This is more evidence of the distorted incentives in U.S. healthcare where health insurance companies profit when patients are denied beneficial care.

Related blog posts:

Le Jardin Exotique, Eze France
Narrow walkways in Eze, France

Comparative Efficacy: Infliximab vs. Ustekinumab

Posted on by

ECL Wong et al. Inflamm Bowel Dis 2023; 29: 1015-1023. Open Access! Comparative Efficacy of Infliximab vs Ustekinumab for Maintenance of Clinical Response in Biologic Naïve Crohn’s Disease

This post hoc analysis included data from separate trials examined the response of 220 biologic-naïve CD participants to either inflximab biosimilar or ustekinumab.

Key findings:

  • Clinical remission: One-year clinical remission (CR) and corticosteroid-free CR rates were similar between infliximab-treated and ustekinumab-treated patients (CR, 66 of 110 [60.0%] vs 63 of 110 [57.3%]; adjusted odds ratio [aOR], 1.15), corticosteroid-free CR, 11 of 28 (39.3%) vs 27 of 51 [52.9%]; aOR, 0.58)
  • Endoscopic response/remission:  infliximab-treated participants were more likely to achieve 1-year endoscopic response (43 of 92 [46.7%] vs 6 of 30 [20.0%], aOR, 3.59) and endoscopic remission (31 of 92 [33.7%] vs 4 of 30 [13.3%]; aOR, 3.35)

In the discussion, the authors note only 1 head-to-head study in CD with ustekinumab. “The SEAVUE trial (NCT03464136) compared adalimumab and ustekinumab among biologic-naïve CD patients. Ustekinumab demonstrated similar efficacy for the achievement of clinical and endoscopic outcomes compared with adalimumab.23 Similar rates of CR at 1 year were reported in SEAVUE (64.9% ustekinumab vs 61% adalimumab) as in our analysis (57.3% ustekinumab vs 60% infliximab)…ustekinumab demonstrated longer retention and lower immunogenicity and has practical advantages over adalimumab, including less frequent dosing intervals (every 8 weeks for ustekinumab vs every 2 weeks for adalimumab) while providing similar efficacy.”

My take: This study suggests that infliximab may be a little better than ustekimumab in biologic-naive patients due to the higher endoscopic response; however, the study was unpowered to provide a definitive answer. A prior study suggested similar endoscopic healing rates (P Riviere et al. Inflamm Bowel Dis 2023; 29: 923-931).

Related blog posts:

Waters off the Cap d’Ail Trail (near Eze, France)

What I Don’t Like About a “Multidisciplinary Approach” for Infants with GERD-Like Symptoms

Posted on by

MH Fishbein et al. JPGN 2023; 77: 39-46. A Multidisciplinary Approach to Infants With GERD-Like Symptoms: A New Paradigm

This was a retrospective study (2011-2019) with 174 full-term infants (<6 months of age). The physician in the study decided which infants needed evaluation by SLP and/or OT.

Key findings:

  • “GERD-like symptoms” were present in 109 with 46 having concerns for dysphagia, 37 having colic/unsettledness, and 26 with concerns combined for dysphagia/colic. 65 were determined to have uncomplicated GER.

The authors conclude that “a multidisciplinary approach, including SLP and OT, is recommended for the evaluation of infants with GERD-like symptoms.” Of note, all but one of the authors are either OTs or SLPs. The authors also promote their AAP book: The CALM Baby Method: Solutions for Fussy Days and Sleepless Nights as a resource for pediatricians and families

Here’s what I don’t like about the recommendations:

  • If taken literally, the authors essentially advocate that a huge percentage of infants need to be seen by OT and SLP as many infants have GERD-like symptoms. The authors cite a review that indicated that 10-25% of infants have GERD symptoms at 1 month; however, other studies have found much higher numbers.
  • While this article stresses the fact that medications are not helpful for GERD symptoms and the importance of not overlooking dysphagia, in my experience many SLPs and OTs are frequently advocating for infants to be placed on GERD medications. In addition, many SLPs and OTs attribute a variety of infant (non-reflux) behaviors to GERD.
  • In many infants with dysphagia, the clinical evaluation by SLP does not have a high sensitivity due to silent aspiration. As such, SLP involvement could be focused on those with objective evidence of dysphagia.

My take: Most infants with GERD-like symptoms do not need to be seen by SLPs or OTs. Dysphagia symptoms (eg. choking, cough with eating, stridor, congestion, poor feeding) need to be evaluated.

Related blog posts:

Coastal Trail, Cap d’Ail, France