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.
JR Ryder et al. N Engl J Med 2024;391:1656-1658. DOI: 10.1056/NEJMc2404054. Ten-Year Outcomes after Bariatric Surgery in Adolescents
Methods: The Teen Longitudinal Assessment of Bariatric Surgery (Teen-LABS) is a prospective multicenter observational cohort study involving adolescents (13 to 19 years of age) undergoing bariatric surgery. Participating adolescents underwent either gastric bypass (161 participants) or sleeve gastrectomy (99 participants) at a mean age of 17 years. Overall, 83% of the 10-year postoperative visits were completed.
Key findings:
The changes in BMI were similar with gastric bypass (mean change, −20.6%) and sleeve gastrectomy (mean change, −19.2%)
Ten years after bariatric surgery, the modeled percentages of participants with remission of coexisting conditions (55% for type 2 diabetes, 57% for hypertension, and 54% for dyslipidemia)
My take (borrowed from authors): “These findings show the long-term durability of weight loss and remission of coexisting conditions after bariatric surgery, as well as the greater health benefits and durability of the effects in adolescents than would be expected in similarly treated adults.”
Related article: H Bliddal et al.N Engl J Med 2024;391:1573-1583. Once-Weekly Semaglutide in Persons with Obesity and Knee Osteoarthritis. Key finding: “treatment with once-weekly injectable semaglutide resulted in significantly greater reductions in body weight and pain related to knee osteoarthritis than placebo.”
A D’Agrosa et al. J Pediatr 2024; 273; DOI: 10.1016/j.jpeds.2024.114129. Cefdinir Stool
This 5 month old infant was brought to ED due to diarrhea and dark stools for 2 weeks. She had completed cefdinir for a UTI.
Cefdinir may cause red or maroon stools when administered with iron or products that contain iron, such as infant formula. This typically occurs within two days of antibiotic administration.
My take: Familiarity with this reaction is helpful to avoid extensive evaluations. Also, it is worthwhile to keep in mind that false-positive testing with guaiac testing is common (up to 34% in healthy infants).
Methods: This was a multisite, randomized comparative efficacy trial of a 1-food (milk) elimination diet (1FED) versus 4-food (milk, egg, wheat, soy) elimination diet (4FED) in pediatric EoE. The 12-week study enrolled 63 patients (6-17 yrs). Primary end point was symptom improvement by Pediatric Eosinophilic Esophagitis Symptom Score (PEESS).
Key findings:
1FED vs 4FED: The mean PEESS improved −25.0 versus −14.5 (P = .04), but remission rates (41% vs 44%; P = 1.00), histology scoring system (−0.25 vs −0.29; P = .77), endoscopic reference score (−1.10 vs −0.58; P = .47), and QoL scores were similar between groups.
The 4FED withdrawal rate (32%) exceeded that of 1FED (11%) (P = .0496).
My take: A 4FED diet is difficult to maintain. In this 12 week study, more than 30% of patients withdrew from the 4FED diet. In addition, dairy elimination alone resulted in similar response rates.
Recently, Dr. Sana Syed gave Children’s Healthcare of Atlanta Grand Rounds. She provided an excellent update on the development of artificial intelligence (AI) to select targeted therapies for pediatric gastroenterology diseases. My notes below may contain errors in transcription and in omission. Along with my notes, I have included many of her slides.
Key points:
One of the goals of using AI is to identify the right therapy at the time of diagnosis. Currently, diseases like eosinophilic esophagitis (EoE) and Crohn’s disease have multiple treatment options. However, many patients do not respond to first-line treatments; many develop complications due to not responding to treatment.
Currently we are lacking adequate biomarkers for individualized therapy. AI has the potential to sort through massive amounts of data (histologic, genetic, pharmacokinetics, transcriptome, metabolomics, etc) to allow for precision therapy.
For EoE, machine-learning has already identified three subtypes that may affect clinical management. EoE1 is associated with a normal-appearing esophagus. EoE2 is associated with being steroid refractory. EoE3, when compared to the other two endotypes, is associated with adult-onset and narrow-caliber esophagus or stricturing.
For Crohn’s disease, research has shown that younger age has been associated with an increased risk of not responding to anti-TNF therapy
This is a quote from President Obama when his administration announced massive funding toward precision medicine in January of 2015, that the promise of precision medicine is ”delivering the right treatments at the right time, every time to the right person.” This figure illustrates some of the kinds of data that Dr. Syed had access to as faculty at UVA, including genomics, epigenome, transcriptomics, proteomics, metabolomics, etc.Shoda and colleagues, used a combination of histology data, endoscopic features, histologic and endoscopic scoring indices, and transcripts that make up the eosinophilic esophagitis diagnostic panel, a quantitative PCR assay with 96 EoE representative genes. The key message from all of those visualizations is that they found that EoE can be divided into three distinct endotypes after analyzing transcriptomics changes via partition-around-medoid clustering, a machine-learning method.In this project, the researcher intend to curate a novel metabolic network specific to the ileum, which is relevant to Crohn’s disease, link metabolic processes with Crohn’s disease phenotypes using in silico metabolic network modeling and ‘omics and characterize and target metabolic pathways in an organoid model generated from patient-derived Crohn’s disease tissue.In CoMPAS, the researchers aim to leverage artificial intelligence methods (AI) methods to build predictive models for CD using histology slides and single-cell RNA sequencing, allowing for risk stratification of B1 patients who will respond to anti-TNF therapyThe goal of our project is to create a multi-omics reference dataset with scRNA-seq data coupled with contextual data on tissue morphology, ancestry, social determinants of health, and the environment. The cohort for this study is enrolling patients who have clinical indications for endoscopy like foreign body removal, reflux, abdominal pain
My take: This work is necessary to identify the right treatments for each patient and will lead to better outcomes. We are already seeing the early stages of machine-learning’s impact on clinical care. In many other fields, AI work is much further along (especially in oncology). A recent study in Nature identified JAK inhibitors as potential life-saving therapy with toxic epidermal necrolysis (TEN).
Reference: Nordmann, T.M., Anderton, H., Hasegawa, A. et al. Spatial proteomics identifies JAKi as treatment for a lethal skin disease. Nature (2024). https://doi.org/10.1038/s41586-024-08061-0
Summary from Eric Topol (Ground Truths) focusing on spatial omics: Thierry Nordmann, Matthias Mann and their international consortium, used deep visual proteomics from 3μm PPFE sections of skin biopsies in patients affected by TEN…
More than 5,000 proteins were quantified from single cells—keratinocyte and immune cells—using mass spec, for the 4 different skin conditions (proteome cluster in Figure below, left panel). This led to the finding that the TEN patients had marked increased in Type 1 and 2 interferon signaling and activation of phosphorylated STAT1, which invoked the janus kinase (JAK/STAT) pathway. Subsequent steps were to test JAK inhibitors in cell culture (with live cell imaging) and in two different mouse models, all showing highly potent, dose-dependent impact on inhibition of the intense inflammatory process and disease severity…
They went on to treat seven patients at Fuian Medical University, the course of one patient shown below, treated with a JAKi on day 4 after diagnosis, and manifesting a marked response starting within 48 hours. All 7 patients fully resolved, with no side effects…
For spatial medicine, there are multiple analytical challenges that invoke the need for machine learning and A.I., including segmentation of cell types, automated capture of cells of microdissection, extracting useful information from the >5,000 proteins quantified per cell, and ultimately, as we’ll see more in the future, A.I. powering the construction of high-resolution 3D maps.
“Vaccines are the first step toward health equity in many parts of the world…Around the globe the measles vaccine has saved nearly 94 million lives over the past 50 years. This and other vaccinations have revolutionized global health…”
“A May study in the Lancet estimated that vaccines against 14 common pathogens have saved 154 million lives over the past five decades—at a rate of six lives every minute. They have cut infant mortality by 40 percent globally and by more than 50 percent in Africa. Throughout history vaccines have saved more lives than almost any other intervention. And vaccines’ promotion of health equity goes far beyond preventing death. The Lancet study found that each life saved through immunization resulted in an average 66 years of full health, without the long-term problems that many diseases cause. Vaccines play a role in nearly every measurement of health equity, from improving access to care, to reducing disability and long-term morbidity, to preventing loss of labor and the death of caretakers…”
“If you have no money, then you want the best bang for the buck, and it’s going to be immunization,” says Seth Berkley, former CEO of Gavi. “For every dollar you invest in immunization, you get $54 of benefit.”
The reduction in mortality equates to 9·0 billion life-years saved.
“In late 2019, when a novel coronavirus detected in Wuhan, China, kicked off one of the largest, deadliest pandemics in a century, everyone looked to the same solution: a vaccine. COVID’s devastation hit poorer countries with less developed health-care systems particularly hard, and in wealthier countries people from underserved and low-income communities suffered higher rates of illness, death and economic hardship…”
“A 2022 study in the Lancet Infectious Diseases estimates that COVID vaccination worldwide prevented 19.8 million excess deaths.”
My take: This is a terrific article and particularly timely given the growing influence of anti-vax proponents. Not only have vaccines prevented millions of deaths, they have helped prevent chronic complications (eg. disability after meningitis). The reduction in mortality in the charts is likely UNDERESTIMATED. Many other vaccines were not included in this estimation: smallpox, human papillomavirus, (HPV), influenza, SARS-CoV-2, Ebola, mpox and other vaccines.
U Bonnet. Gastroenterol 2024; 167:1054-1055 (letter). Cannabis Hyperemesis Syndrome Recovers Completely When the Use of Cannabis or Synthetic Cannabinoids Is Permanently Discontinued—Cyclic Vomiting Syndrome Does Not
ME Mullins et al. Gastroenterol 2024; 167: 1055-1056 (letter). Comments on the AGA Clinical Practice Update on Diagnosis and Management of Cannabinoid Hyperemesis Syndrome
The correspondence regarding AGA’s clinical practice update on Cannabinoid Hyperemesis Syndrome offered a few useful points.
Bonnet notes that “CVS is most likely present if cyclic vomiting persists, recurs or worsens during cannabis abstinence (beyond 3-week cannabis withdrawal period, which may be temporarily accompanied by nausea). In other cases with more fluctuation symptoms, a clear distinction between CHS and CVS is not so easy…Evidence shows that a symptom-free period of about 12 months after cessation of long-term cannabis use should be sufficient to clearly distinguish CHS from CVS…Finally, I emphasize here that…CHS…in exceptional cases can lead to life-threatening conditions (eg due to prerenal failure, severe electrolyte disturbances, or esophageal rupture)…but recovers completely when affected patients permanently stop using cannabis or THC analogues.
Mullins et al note that “ondansetron is uniformly ineffective and that butyrophenones (haloperidol, droperidol) are more effective” for CHS. In the reply, the authors note that the data supporting these medications is based on small studies and some patients have developed acute dystonia.
Guidance recommends use of resmetirom (in adults) with F2-F3 fibrosis as determined by “imaging-based NILDAs, such as liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE) or magnetic resonance elastography (MRE)…liver biopsy is not typically recommended for fibrosis staging in current clinical practice, [though] histologic examination remains the gold standard to quantify fibrosis.”
“Glucagon-like peptide 1 (GLP-1) and GLP-1/glucose-dependent insulinotropic polypeptide (GIP) receptor agonists are FDA approved for the treatment of type 2 diabetes and overweight/obesity. They reduce the risk of cardiorenal complications in addition to their effects on glycemic control and weight loss.17–25 While these pharmaceutical agents are not currently approved for the treatment of MASH, phase 2 randomized, placebo-controlled clinical trials of liraglutide, semaglutide, and tirzepatide have demonstrated their efficacy in reducing steatohepatitis without worsening fibrosis and, in the case of tirzepatide, decreasing fibrosis without worsening of steatohepatitis as well.”
“The most common treatment-emergent adverse events were diarrhea and nausea, which developed in 24% to 34% and 12% to 22% of resmetirom-treated participants, respectively…Development of hypothyroidism requiring levothyroxine replacement occurred in 1.8% of participants receiving resmetirom.”
The authors recommend assessing response with bloodwork and noninvasive imaging at 1 yr to help determine if therapy should be continued.
My take: This article provides practical advice for using resmetirom for MASLD.
In this multicenter retrospective review with 183 patients, the adalimumab (ADM) levels were examined with respect to healing of perianal fistulas. Most patients (82%) had complex perianal fistulizing CD.
Key findings:
87 patients (48%) received intensified dosing at the time of therapeutic drug monitoring (TDM)
Patients with complete fistula healing (CFH) had higher median ADM levels: 12.9 compared to 6.1 for those witout CFH
“Optimal ADM concentration associated with CFH was 12.2 mcg/mL” which had positive predictive value of 64% and negative predictive value of 80%. Among those with ADM >12.1, CFH was achieved in 64% compared to 20.5% in those with concentrations <12.1 (Odds ratio, 5.7). “Even higher drug levels may be needed.”
There were 46 patients in each drug level category
My take: There is a lot of data supporting TDM, including proactive TDM, with anti-TNF agents like adalimumab and infliximab. This study shows that with fistulizing disease higher drug levels are needed to achieve better outcomes.
From Caitlyn Rivers Newsletter, Force of Infection 11/4/24:
Norovirus is high and increasing right now. Nationally, test positivity is at nearly 12%. To put this in context, the peak last year was 13.6%. Rates are particularly high in the Southern region.
A reminder as cases increase: norovirus causes stomach pains, diarrhea, and vomiting. It is extremely transmissible via bodily fluids and through contaminated surfaces, food, and water.
To reduce your odds of getting sick, remember to wash your hands frequently with soap and water for at least 30 seconds (norovirus is able to withstand hand sanitizer).
If you or someone in your household becomes sick, wash hard surfaces with soap and water or a diluted bleach mixture, and wash soiled clothing and linens in hot water and then dry on high heat.
Norovirus is still highly transmissible for several days after symptoms improve or go away. As such, insofar as is possible, avoid preparing food for others for at least 72 hours after symptoms end. Longer is better: it can spread up to two weeks after symptoms end, though it is most transmissible during those first few days of illness and after symptoms resolve.
gutsandgrowth 