This retrospective review of 24 children with tethered cord syndrome (TCS) (50% female) who had ARM testing (median age at ARM 6.0 years). 19 children had prior TCS repair.
Key findings:
No significant differences in ARM parameters were found between children who had detethering surgery before ARM and children with functional constipation (FC). The children with TCS did have lower resting pressures though this was attributed to most having their ARM while under GA for concurrent procedures. The resting pressures were still normal.
Among the 14 children who also had a colonic manometry (CM) performed (13/14 after detethering surgery), there were no significant differences in colonic motility were found between children with a history of TCS and children with FC.
My take: The vast majority of children with a history of TCS (following detethering) should be treated akin to children with functional constipation.
Impression, Sunrise by Claude Monet at National Gallery of Art (Washington, D.C.)
Methods: The participants (n=96 adults) in the combination of Healthy Low Carbohydrate Diet (HLCD) and Time Restricted Eating (TRE group were provided with HLCD and instructed to follow the 10-h TRE. The HLCD … consisted of approximately 30% of total energy from carbohydrates, 50% from fats, and 20% from proteins. Moreover, compared to a traditional low-carbohydrate diet that only focused on carbohydrate restriction, HLCD also emphasized healthy food sources and high-quality macronutrients such as unsaturated fatty acids, plant proteins, and high-quality carbohydrates, including whole grains, fresh vegetables, and fruits. Additionally, 25–35 g of mixed nuts were provided along with HLCD per day, which mainly included walnuts, peanuts, cashews, pistachios, pecans, almonds, and hazelnuts. 10-h TRE required participants to consume the provided meals within 10 h each day. Outside the eating window, only water, and noncaloric beverages were allowed.64
Key findings:
Each of the patient groups lost between 2.57 to 4.11 kg
HLCD was more effective in reducing fat mass
Both dietary interventions resulted in changes in the microbiome
My take: It is still to work on improving diet quality and improving exercise –only a small percentage of patients will be receiving GLP-1 drugs or bariatric surgery. The Mediterranean diet likely has the most data supporting its use for obesity.
This study correlated environmental toxins and steatotic liver disease. Four hundred and thirty-five children distributed across MASH (n = 293) and MASLD (n = 142), with 304 (69.9%) males. Toxins analyzed: PFAS chemicals included perfluorohexane-1-sulphonic acid (PFHXS), perfluorononanoic acid, perfluorooctanoic acid, and perfluorooctanesulfonic acid and PBDE included 2,2′,4,4′-tetrabromodiphenyl ether (BDE47), 2,2′,4,4′,5-pentabromodiphenyl ether (BDE99), and 2,2′,4,4′,6-pentabromodiphenyl ether (BDE100).
Key findings:
There was an inverse association between PFAS/PBDE mixture and MASH versus MASLD, lobular inflammation (p = 0.026), NAS (p = 0.009, FDR p = 0.04), and log-transformed ALT (p = 0.005, FDR p = 0.025) driven by perfluorohexane sulfonate (PFHXS).
PFASs were detected in 290 (67%) samples, showing the pervasive nature of this chemical exposure in children
My take: Not surprisingly, our environmental exposures influence the severity of steatotic liver disease. There is widespread exposure to pollutants and the full toll on our health is not clear.
Å Sjöholm et al. N Engl J Med 2024;391:1528. Glycogenic Hepatopathy
Case report: “An 18-year-old man with type 1 diabetes mellitus who had been admitted to the hospital with diabetic ketoacidosis had unexpected elevations in aminotransferase levels. Laboratory studies showed a peak alanine aminotransferase level of 972 U per liter.”
“Computed tomography of the abdomen showed hepatomegaly without parenchymal changes (Panel A). A liver biopsy showed swollen hepatocytes with abundant deposition of glycogen in the cytoplasm, as evidenced by positive staining with periodic acid–Schiff (Panel B) and digestion of the deposits after treatment with diastase (Panel C).”
“At follow-up 3 weeks after discharge from the hospital, the patient had been adherent to insulin therapy, and his aminotransferase levels had normalized.”
My take: The potential etiologies for elevated liver enzymes in the setting of diabetic ketoacidosis include glycogenic hepatopathy, ischemic hepatitis, infectious etiologies, autoimmune hepatitis, celiac disease, and steatotic liver disease. This recent case report describes glycogenic hepatopathy. There was not a discussion as to why a CT scan and a liver biopsy were deemed necessary.
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.
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