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.
“ZYMFENTRA is approved for maintenance therapy in adults with moderately to severely active ulcerative colitis (UC) or moderately to severely active Crohn’s disease (CD) following an induction treatment regimen with an infliximab product administered intravenously. The recommended dose of ZYMFENTRA for maintenance treatment is 120 mg every two weeks.”
” ZYMFENTRA is considered a new biologic with a first-approved subcutaneous administration form and thus will be under patent protection for its dosage form by 2037 and for its route of administration by 2040.”
My take: If the cost of the subcutaneous infliximab is competitive with the intravenous formulations, then this is going to result in a lot less infusions. Currently, this product does not have a pediatric indication. Projected cost per internet search: $6,181.08 for two shots over four weeks.
R Marfella et al. NEJM 2024; 390: 900-910. Microplastics and Nanoplastics in Atheromas and Cardiovascular Events
The authors conducted a prospective, multicenter, observational study involving patients who were undergoing carotid endarterectomy for asymptomatic carotid artery disease with 257 patients who completed a mean follow-up of 34 months.
Key findings:
Polyethylene was detected in carotid artery plaque of 150 patients (58.4%), with a mean level of 21.7±24.5 μg per milligram of plaque; 31 patients (12.1%) also had measurable amounts of polyvinyl chloride, with a mean level of 5.2±2.4 μg per milligram of plaque.
Electron microscopy revealed visible, jagged-edged foreign particles among plaque macrophages and scattered in the external debris.
There was a 4.5 -fold increase of the composite of all-cause mortality, heart attack and stroke in patients in whom microplastics and nanoplastics (MNPs) were detected within the atheroma than in those in whom these substances were not detected (hazard ratio, 4.53)
“Panel A shows transmission electron microscopy images of particles of high internal electron transparency contoured by a very thin electron opaque line. These particles do not resemble usual organic material owing to their particularly irregular shape. These particles (arrows) were detected inside living macrophages and outside in the amorphous material of the plaque (arrows).”
Discussion notes that “according to a World Health Organization statement, MNPs larger than 150 μm or 10 μm in diameter, respectively, are not absorbed into blood and do not penetrate blood vessels.25 Our findings suggest that nanoplastics, rather than microplastics, might accumulate in sites of atherosclerosis…Given the wide distribution and availability of MNPs, the attribution of all potential sources in humans is nearly impossible.”
“It is important to note that our results do not prove causality. The association between the presence of MNPs within plaque and the incidence of a composite of cardiovascular disease or death outcomes may also entail the risk from exposure to other residual, unmeasured confounding variables.”
Image available on X (formerly called twitter)
The associated editorial (PJ Landrigan. NEJM 2024; 390: 948-950) provides some additional context and notes the need for wide-scale transition form fossil carbon.
Key points:
“Plastics have enabled extraordinary advances in virtually every area of medicine and have made our lives immeasurably more convenient. Multiple lines of evidence now indicate, however, that plastics are neither as safe nor as inexpensive as they seem. The benefits of plastics come at great and increasingly visible costs to human health and the environment.”
“Plastics comprise a polymer matrix plus thousands of chemical additives that impart such properties as color, stability, flexibility, flame resistance, and water repellency. Many additives are toxic; these include carcinogens, neurotoxicants, and endocrine disruptors such as bisphenols and perfluorinated and polyfluorinated substances that can disrupt lipid metabolism and increase the risk of diabetes, cardiovascular disease, and stroke.2“
“Worldwide, the annual output … to approximately 400 million tons today.3 This output is projected to double by 2040 and triple by 2060…Disposable, single-use items account for about 40% of current production and contribute disproportionately to the accumulation of plastic waste.”
” Data from the National Biomonitoring Surveys of the Centers for Disease Control and Prevention (https://www.cdc.gov/biomonitoring/index.html. opens in new tab) suggest that plastic additive chemicals are present in the bodies of nearly all Americans. The Minderoo Monaco Commission has concluded that plastics endanger human health at every stage of the plastic life cycle.1“
My take: This study provides further evidence that plastics, while incredibly important and convenient, take a huge toll on the environment and are increasingly recognized as having harmful effects on the the human body. In the same issue, is a review article “Health Effects of Fossil Fuel-Derived Endocrine Disrupters.” However, trying to reduce our dependence on plastics is not going to be easy.
This retrospective study enrolled 47 patients receiving maintenance ustekinumab (UST) for Crohn’s disease. Over one-third of patients (n = 18, 38.3%) were on higher than standard dosing of 90 mg every 8 weeks. The study utilized drug-tolerant ELISA assay for UST trough levels and drug antibody titers.
Key findings:
In this observational cohort of patients with CD on maintenance UST, 63.8% of patients (n = 30 of 47) had achieved mucosal healing at time of level assay, and 85.1% (n = 40 of 47) had achieved at least mucosal response.
Patients with mucosal healing (n = 30) had significantly higher mean serum UST levels (5.7 µg/mL, SD 6.4) compared with those with no response (1.1 µg/mL, SD 0.52; n = 7, P < .0001).
Patients with mucosal healing (n = 30) had significantly higher mean serum UST levels (5.7 µg/mL, SD 6.4) compared with those with no response (1.1 µg/mL, SD 0.52; n = 7, P < .0001)
Similarly, for patients with mucosal response (n = 40), we observed a higher mean serum UST trough level (5.1 µg/mL, SD 6.1) compared with those with no response (1.1 µg/mL, SD 0.52; n = 7, P < .0001).
There were no antidrug antibodies detected in the cohort.
Discussion:
Unlike anti-TNF therapeutic drug monitoring, “there are few data supporting a correlation between serum ustekinumab levels and MH. The STARDUST randomized control trial34 is studying standard of care compared with treat-to-target ustekinumab therapy and has reported preliminary data at 1-year showing superiority of treat-to-target approaching achieving endoscopic response.”
My take: In this study, patients with UST levels above 2.3 μg/mL had a 10-fold level higher likelihood of mucosal healing and mucosal response. UST therapeutic drug monitoring can help “determine true nonresponse rather than insufficient dosing in patients who have not responded to UST.”
Other studies have suggested higher target levels. Mayo clinic lab site: “Concentrations > or =4.5 mcg/mL are associated with mucosal healing.” Ref: Papamichael K, Cheifetz AS, Melmed GY, et al. Appropriate therapeutic drug monitoring of biologic agents for patients with inflammatory bowel diseases. Clin Gastroenterol Hepatol. 2019;17(9):1655-1668.e3
Mean through serum ustekinumab levels with standard deviation in patients who had achieved mucosal healing (n = 30), mucosal response (n = 40) or nonresponse (n = 7).
We had an brilliant lecture given to our group by Danielle Wendel who leads Seattle Children’s Intestinal Rehabilitation team. My notes below may contain errors in transcription and in omission. In addition, the information provided is based on what is done in Seattle. However, there is not a lot of evidence for much of what is done in intestinal rehabilitation. Thus, there is variation in practice at different centers and what works for one patient might not work for another. Following my notes, I have included many of her slides (same slides as yesterday’s post).
CLABSI Pointers:
-At Seattle, with suspected CLABSI, usually central blood culture obtained without peripheral blood culture. (Peripheral blood cultures have not helped their team improve management)
-Everyone with SBS and with fever (greater than or equal to 100.4) stays for at least 48 hrs on broad spectrum IV antibiotics (choice based on local sensitivities) through the central line until it is conclusively determined if they have a CLABSI (which still carry a significant mortality risk)
-Sodium bicarbonate lock experience has been good (8.4% solution, 1.5 mL lock for the entire time off PN in all tunneled CVL flushed in at the end of the dwell). It has become a good substitute for ethanol locks. Their experience will be published soon. Since sodium bicarbonate lock does not need to be withdrawn, it has been associated with less line breakage. Several lock solutions (KiteLock and Taurolidine) are not currently available in the U.S. KiteLock is about to be studied in Seattle.
-At Seattle, all CLABSI are treated through the line and every effort is made to salvage and/or repair lines. Line replacement increases risk of losing central IV access.
-Line is removed for fungal infections
-The Seattle team prefers tunneled CVC
SIBO Pointers:
-Testing is problematic. Breath tests are not reliable in kids with SBS. Duodenal aspirates are often not helpful and have a number of technical difficulties; also, it is unclear whether a duodenal aspirate is representative of the bacteria in the more distal bowel.
-Metronidazole is their first line choice. Gentamicin (IV formulation given enterally) is their 2nd choice. Rifaximin is their 3rd line. Rifaximin would possibly be used earlier in treatment except for difficulty getting covered. When used, they crush up pills rather than have it compounded to avoid sweeteners.
Teduglutide
-Best to start if a patient is is > 1yo and on stable TPN (not able to wean)
-Make sure patient is using a tiny needle (not adult needle in package)
-Anticipate long-term treatment (?indefinite)
GI Bleeding Pointers:
This is being seen frequently.
Etiologies include anastomotic ulcers and IBD-like lesions. If a patient is not improving with standard approaches and possibly resection, could need an anti-TNF type agent.
At Seattle, they are very selective about patients appropriate for a STEP procedure as this may be associated with more frequent bleeding over time due to the many staples used. Hand-sewn tapering may be a better option for many patients.
With the challenging decisions required for these bleeding patients, discussion with an experienced intestinal rehab center may be helpful.
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.
We had an brilliant lecture given to our group by Danielle Wendel who leads Seattle Children’s Intestinal Rehabilitation team. My notes below may contain errors in transcription and in omission. In addition, the information provided is based on what is done in Seattle. However, there is not a lot of evidence for much of what is done in intestinal rehabilitation. Thus, there is variation in practice at different centers and what works for one patient might not work for another. Following my notes, I have included many of her slides.
Key points:
Enteral nutrition is key for adaptation. At Seattle, oral feeds rather than GT feeds are preferred.
Time is the thing that helps the most. Unclear which additives help.
Though prediction models often look at >50 cm, it is important to counsel families, even with more bowel length, that the care is going to be quite challenging.
Acid suppression can be helpful in the early phase after resection especially if problematic high stoma output.
Iron: if given enterally, typically given everyday or every other day. Iron dextran can be given in TPN (cannot be given with lipids). Ferric carboxymaltose is a good choice for parenteral administration. Due to the need for few infusions (~1-2 per year), it is safer (less line entry) and cost-effective compared to iron sucrose.
Seattle shares an “Emergency Care Letter” with their patients (template available in EPIC)
Yearly doppler ultrasound is recommended to assess vascular access.
If a patient has more than one thrombosis, the Seattle team recommends long term prophylaxis, though it might take treatment levels to prevent further thrombosis.
SMOFlipid is the most frequently used lipid at Seattle. It can be given in higher doses than Omegaven which is important nutritionally; omegaven is generally given at only 1 to 1.5 mg/kg/day and used for treatment of IFALD.
Long term outcomes are just as good with chronic TPN as with intestinal transplantation. So, referral generally needed based on complications like losing central access (3 of 4 upper central sites) or progressive liver disease.
Diet Pointers:
-In infancy, standard formula and breastmilk are preferred and thought to help with adaptation. Some infants need elemental diets but it is not routinely given across the board (some other institutions feel strongly about using elemental diets, but there is limited data)
-Kids with short bowel syndrome may tolerate volume better than concentration
-The Seattle program strictly restricts sweet tasting food/drink for first 3-4 years of life to help educate the child’s palate and recommends limiting these food/drink for IF patients in general.
-Addition of solid foods usually helps with stoma output
Nutrient Monitoring Pointers:
Usually best to batch them all lab tests for micronutrients [many micronutrients are affected by inflammation and this may affect timing of lab testing]
At Seattle, aluminum and manganese are not routinely checked as they are contaminants in PN that cannot be removed
Serum thyroid testing is a marker for iodine deficiency in patients receiving most of their calories from PN (>70) which may be more frequent now that betadine is not used for dressing changes. Their goal for urine iodine is >100 (can be treated with ultra-diluted potassium iodide which needs to be compounded by the pharmacy)
When testing for EFA (essential fatty acid) deficiency, lipids should be off for 4 hrs (or more). Urinalysis is checked to monitor for chronic kidney disease. Urine sodium goal is >30 and is checked quarterly in patients with high ostomy output or excessive rectal stool output with poor growth.
Hypokalemia may be a sign of total body sodium depletion due to the kidneys dumping potassium to conserve sodium
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.
“Globally, Covid ranks among the worst killers since 1900. AIDS, for example, is estimated to have killed about 40 million people, but over a half century rather than only four years. The 1918 flu killed somewhere between 20 million and 50 million people.”
“Among high-income countries, the U.S. has had one of the highest Covid tolls. The excess-death rate here, as a study by Jennifer Nuzzo and Jorge Ledesma of Brown University notes, has been much higher than in Canada, Britain, Germany, France, Spain, Sweden, Denmark, Japan, South Korea or Australia…”
“Many Americans, especially political conservatives, were skeptical of the vaccines despite overwhelming evidence of their effectiveness. To this day, more than 30 percent of self-identified Republicans have not received a Covid vaccine shot, compared with less than 10 percent of Democrats…You can see the tragic effects of vaccine skepticism in this chart.“
“While many liberals exaggerated the value of pandemic restrictions, they were right about the vaccines. “
According to data from Washington State in 2023, the death rate for those older than 65 years due COVID-19 was nearly double in those unvaccinated compared to those who had been boosted. In the younger age group, 35-64, the rate of fatal infection was much lower but remained 5 times as high in those unvaccinated compared to those who had been boosted.
My take: COVID-19 has exacted a tremendous toll and these articles do not even focus on long COVID which afflicts so many people as well.
Some of the input from this video was from physicians in our ImproveCareNow consortium (personal communication). Here’s an key points/excerpt: Prior Authorization Video (8:37 minute video)
This video explains how insurance companies have ‘weaponized’ prior authorization to postpone and/or deny care in order to increase their profits. “This is medical injustice disguised as paperwork.”
The video states that ~80% of PAs are effective in preventing patients from getting the care their physician recommended. However, when physicians spend their time appealing denials, they are usually successful in getting the medication covered.
“Prior authorization gives your insurance company more power than your doctor.”
There are efforts in Congress, including the GOLD Card Act of 2023, aimed at reforming prior authorization.
My take: Prior authorization delays and denials of care sometimes have devastating consequences (watch the video)
The authors used data from 3663 population-based studies with 222 million participants that measured height and weight in representative samples of the general population.
Key findings:
More than a billion people globally are now considered obese.
Obesity has more than quadrupled among children and adolescents since 1990.
Among all adults, 43 percent were overweight in 2022.
The combined burden of underweight and obesity has increased in most countries, driven by an increase in obesity, while underweight and thinness remain prevalent in south Asia and parts of Africa.
The trend of increasing obesity prevalence was present in adults and children (5-19 years).
Age-standardized prevalence of obesity increased by more than 20 percentage points in 49 countries (25%) for women and 24 countries (12%) for men, and by as much as 33·0 percentage points in The Bahamas for women and 31·7 percentage points in Romania for men.
My take: This is an impressive study providing extensive data on what’s happening with weight trends. Clearly, there is an urgent need for obesity prevention.
F Muller et al. NEJM 2024; 390: 687-700. CD19 CAR T-Cell Therapy in Autoimmune Disease —A Case Series with Follow-up
JD Isaacs. NEJM 2024; 390: 758-759. (editorial) CAR T Cells — A New Horizon for Autoimmunity?
Methods: This case series enrolled 15 patients with severe SLE (8 patients), idiopathic inflammatory myositis (3 patients), or systemic sclerosis (4 patients) who received a single infusion of CD19 chimeric antigen receptor (CAR) T cells after preconditioning with fludarabine and cyclophosphamide. All patients were refractory to at least two conventional therapies.
Key findings:
Median follow-up was 15 months.
All the patients with SLE had DORIS remission, all the patients with idiopathic inflammatory myositis had an ACR–EULAR major clinical response, and all the patients with systemic sclerosis had a decrease in the score on the EUSTAR activity index.
Immunosuppressive therapy was completely stopped in all the patients without having relapses or worsening of their disease.
Some points from the editorial:
“Similar outcomes [as CAR T-cell infusion] can sometimes be achieved with autologous stem-cell transplantation but with a risk of substantial toxic effects and even death”
The editorial explains the potential mechanisms of how CD19 CAR T-cells therapy works in comparison to CD20 monoclonal antibodies like rituximab. “Whereas rituximab primarily depletes B cells with some secondary loss of plasmablasts, CD19 CAR T-cells have direct cytotoxicity for plasmablasts and many plasma cells.”
“The future trajectory of CAR T-cell therapy for autoimmunity will be driven by efficacy, safety, cost, and acceptability… if extended follow-up reinforces the current data, the benefit-to-risk ratio is likely to prove acceptable to both physician and patient, at least in certain cases of refractory disease. Therapy is individualized, difficult to scale, and expensive.”
Long-term safety for CAR T therapy is still poorly understood. Recently a report identified secondary cancers in patients who have received this treatment for oncologic diseases (Verdun N, Marks P. Secondary cancers after chimeric antigen receptor T-cell therapy. N Engl J Med 2024;390:584-586)
My take: For now, almost all autoimmune diseases will be treated with indefinite conventional agents. Nevertheless, it is a hopeful step that a cure for these diseases may be possible.
Methods: This retrospective cohort study analyzed electronic health record data of 603,051 adolescents aged 13 to 17 years between January 1, 2018, and December 31, 2021
Key findings:
4.4% (1 in 23) of all adolescents met the eligibility criteria for bariatric surgery.
22.2% had obesity (12.9% class 1, 5.4% class 2, and 3.9% class 3).
The most frequently diagnosed comorbid conditions were gastroesophageal reflux disease (3.2%), hypertension (0.5%), and nonalcoholic fatty liver disease (0.5%).
The authors estimate that ~1 million U.S. adolescents meet criteria for bariatric surgery though only ~1700 receive this treatment yearly
The study strongly demonstrates that the comorbid conditions associated with obesity are underdiagnosed. In some cases this is because the screening is not done; yet, in other cases, despite screening, comorbid conditions go undiagnosed. For example, the prevalence of hypertension based on having at least 3 elevated BP measurements was 10 times higher than the prevalence based on the diagnosis being made (ICD 10) codes
My take: A lot of kids meet criteria for bariatric surgery but few undergo this surgery. If effective anti-obesity medications become more widely adopted (affordable), this may be a preferable option to surgery, especially in the pediatric age group. Surgery could be deferred to those who did not respond. Also, immediate implications of the study are that we need to be more diligent about looking for associated health problems (eg. OSA, HTN, T2DM, MASLD).
gutsandgrowth 