While mass shootings are occurring frequently and garner a lot of press, everyday children and adults are dying from more ‘mundane’ tragedies. To reduce some these –a recent AAP message: Is There an Unlocked Gun Where Your Child Plays?
Parents need to ask this question to protect their children.
A recent study (C Stiles-Shields et al. JPGN 2018; 66: 71) reports on 32 cases of median arcuate ligament syndrome (MALS) from a single center, 2011-17. To me, this is an astounding number of individuals who were operated on for this disorder. As the authors note, “MALS remains a controversial and vexing condition. 13% to 50% of healthy patients may exhibit radiographic features of celiac artery compression.”
While the authors note that pain symptoms improved significantly, they report that “comorbid psychological conditions were common, occurring in about half the sample before and after surgery.”
My take: If one finds celiac artery compression and suspects MALS, it is unclear to me if an operation is indicated and how to determine when it is indicated.
Related blog post:
Proctor Creek Trail
A recent study (DY Graham, A Tansel. Clin Gastroenterol Hepatol 2018; 16: 800-808) analyzed 56 randomized trials to determine relative potency of proton pump inhibitors (PPIs) based on time in which intragastric pH was 4 or less (pH4time).
Key findings:
The authors note that peak effectiveness for PPIs was at ‘approximately 70 mg of omeprazole equivalents’. In addition, they state that twice a day dosing was more effective than increasing once a day dosing; however, three times a day dosing was not more effective than twice a day. “Dexlansoprazole, a quasi-twice-a-day formulation produced similar acid suppression to the lowest twice-daily PPI regimen and 20 mg vonoprazan once daily provided similar efficacy aas high-dose twice-daily PPI.” The authors also compare costs; generics of pantoprazole, omeprazole, and esomeprazole cost as little as $0.02-0.04 per omeprazole equivalent. Thus, 20 mg of omeprazole would be as little as 40 cents.
My take: Using the lowest effective dose of a PPI is recommended. In patients needing higher dosing or with suboptimal response to acid suppression, this data can be very helpful.
Proctor Creek Trail
A recent study (J Kirkegard et al. Gastroenterol 2018; 154: 1729-36) determined that acute pancreatitis is associated with an increased risk of pancreatic cancer. This finding is based on a nationwide (Denmark), matched cohort study of all patients admitted with acute pancreatitis from 1980 to 2012. This involved 41,669 patients with acute pancreatitis and 208,340 comparison subjects.
Key finding:
Limitations: While this study is based on a Danish registry, the authors note that the data had been prospectively entered and has a high validitiy.
My take: While I have not seen pancreatic cancer in the pediatric population, it is concerning that episodes of pancreatitis are likely to increase this risk for the children as well (over their lifetimes).
Mountain Laurel (?) -Pine Mountain Trail
Typically, most pediatric gastroenterologists want to remember that the gross appearance of the liver in patients with Dubin-Johnson is black as this is rumored to be a frequently asked question for board testing. Practically, though other features are important to recognize since the color of the liver is not readily evident except during surgery. As such, a recent retrospective study (T Togawa et al. J Pediatr 2018; 196: 161-7) describes 10 neonatal patients from Japan.
Key findings:
The clinical course was similar in the patients:
My take: Dubin-Johnson syndrome is much easier to identify with the availability of genetic panels.
Related blog post: Dubin-Johnson Syndrome
A recent case series (Li H, A Diaz-Kuan, M Vos et al. Mol Genet Metab. 2018 Apr;123(4):428-432) highlights the importance of dietary history in infants with liver failure (abstract below). Congratulations to my colleague Miriam Vos one of the coauthors.
Commentary on this publication from Emory News (from Kipp Ellsworth’s twitter feed):
Babies with inherited intolerance of fructose face a risk of acute liver failure if they are fed certain widely available formulas containing fructose, pediatricians and geneticists are warning. Baby formula manufacturers should remove fructose or sucrose, or explicitly label their products to allow parents to avoid those sweeteners if necessary, the doctors say.
In a recent paper in Molecular Genetics and Metabolism, Emory geneticists Hong Li, MD, PhD and Michael Gambello, MD, PhD together with Children’s Healthcare of Atlanta pediatric hepatologist Miriam Vos, MD and colleagues report four cases of hereditary fructose intolerance (HFI), all diagnosed in early infants. All had acute liver failure that resolved when the infants switched to formula without fructose.
HFI is estimated to occur in 1 out of 20,000 live births. It comes from mutations in the aldolase B gene, resulting in an inability to metabolize fructose. Early symptoms include nausea, vomiting, abdominal pain and failure of an infant to gain weight. If unrecognized, HFI can result in liver and kidney damage, seizures or death.
HFI-related problems do not appear if an infant is being breastfed exclusively. It is normally recognized when fructose-containing solid foods, such as fruit, are introduced into the diet several months after birth. However, some baby formulas – often soy-based – contain sweeteners such as high-fructose corn syrup or sucrose (table sugar), which is made of fructose and glucose linked together. Sometimes, the label only says “sugar” instead of sucrose…
Since HFI is a treatable disease, Li urges pediatricians to consider HFI as a potential diagnosis if there is a feeding problem, elevated transaminase enzymes or jaundice (a sign of liver damage) and the infant has been fed formula containing fructose or sucrose.
Some information about a young patient’s condition can be obtained from urine carbohydrate tests, but the only way to confirm HFI is by genetic sequencing.
Abstract:
Hereditary fructose intolerance (HFI) is an autosomal recessive disorder caused by aldolase B (ALDOB) deficiency resulting in an inability to metabolize fructose. The toxic accumulation of intermediate fructose-1-phosphate causes multiple metabolic disturbances, including postprandial hypoglycemia, lactic acidosis, electrolyte disturbance, and liver/kidney dysfunction. The clinical presentation varies depending on the age of exposure and the load of fructose. Some common infant formulas contain fructose in various forms, such as sucrose, a disaccharide of fructose and glucose. Exposure to formula containing fructogenic compounds is an important, but often overlooked trigger for severe metabolic disturbances in HFI. Here we report four neonates with undiagnosed HFI, all caused by the common, homozygous mutation c.448G>C (p.A150P) in ALDOB, who developed life-threatening acute liver failure due to fructose-containing formulas. These cases underscore the importance of dietary history and consideration of HFI in cases of neonatal or infantile acute liver failure for prompt diagnosis and treatment of HFI.
Related blog post: Changing Approach to Neonatal Acute Liver Failure
Chattahoochee River Near Island Ford
Briefly noted: J Remmler et al. Clin Gastroenterol Hepatol 2018; 16: 730-7. This retrospective study with 474 patients showed that blood levels of interleukin 6 were associated with mortality. In this cohort, those with levels in the lowest quartile (< 5.3 pg/mL) had zero fatalities within 1 year. In those with the highest quartile (37 pg/mL or more), had a 67.7% mortality rate within 1 year. The associated editorial (pg 630-32) notes that IL6 functions include liver regeneration, infection defense, and metabolic homeostasis. “IL6 is synthesized during inflammatory conditions…persistent activation of the IL6 pathway may have detrimental effects in the livers and in other tissues.”
Pine Mountain Trail
Another treatment is emerging for biliary cholangitis (PBC): C Corpechot et al (NEJM 2018; 378: 2171-81) shows that an inexpensive medication, bezafibrate, is effective in patients with PBC who have not responded adequately to ursodeoxycholic acid. An associated editorial (2234-35 by Elizabeth Carey) notes that this medication is not available in the U.S., though a similar medicine, fenofibrate “has shown similar efficacy” in PBC (off-label).
AL Granstrom et al. JPGN 2018; 66: 398-401. Using a nationwide Swedish registry, the authors determined that patients with a Hirschsprung disease had an increased risk of receiving a diagnosis of IBD (OR 4.99). In total 20 of 739 HD patients, developed IBD.
T Card et al. Inflamm Bowel Dis 2018; 24: 953-9. This article questions the ‘what is the risk of progressive multifocal leukoencephalopathy ..with vedolizumab? The authors are not certain. But they state that after reviewing 54,619 patient-years “there have been no cases of PML reported in association with vedolizumab use.”
LCT Buer et al. Inflamm Bowel Dis 2018; 24: 997-1004. This case report of 10 patients describes combination therapy with anti-TNF therapy with vedolizumab. “At the end of follow-up, all patients were in clinical remission, and 8 patients could discontinue anti-TNF treatment.”
OJ Adedokun et al. Gastroenterol 2018; 154: 1660-71. This study examined pharmocokinetics and response of ustekinumab in patients with Crohn’s disease from 701 patients in phase 3 studies.. “Trough concentrations was approximately threefold higher in patients given ustekinumab at 8-week intervals compared with 12-week intervals…Trough concentrations of 0.8 (or even up to 1.4 mcg/mL) or greater were associated with maintenance of clinical remission.” Also, “concentrations of ustekinumab did not seem to be affected by cotreatment with immunomodulators.”
View from Pine Mountain
A recent study (ME McSweeney et al. JPGN 2018; 66: 887-92) determined that preoperative characteristics were unable to determine which patients who had gastrostomy tube (GT) placement would ultimately need conversion to gastrojejunostomy (GJ) placement.
This retrospective study matched 79 GJ patients with 79 GT patients.
Key points:
While not a result in the study, the issue of GJ compared with fundoplication is briefly discussed. The authors in their discussion of preoperative workup state that
“the complications of fundoplication are more significant and the risks are higher than GJ placement”
In my view, this is one of the most consequential parts of their discussion. While the authors have extensive experience, I think the issue regarding GJ tube placement and fundoplication is more murky. GJ tubes can be difficult to maintain and I have not seen long-term well-controlled studies comparing outcomes between GJ placement and fundoplication.
Other pointers in the discussion:
My take: This is an important retrospective study that illustrates how difficult it is to know preoperatively which patients need GJ placement (or fundoplication) compared to GT placement alone. In our institution, we are reluctant to place GT placement if a patient has not demonstrated tolerance of nasogastric feeds.
Related blog posts:
Amelia Island
gutsandgrowth 