SMOF Neurodevelopmental Data Looks Good –In Five Years We’ll Know More

A recent study (C Binder et al. J Pediatr 2019; 211: 46-53) examined electrophysiological brain maturation in a randomized double-blinded controlled trial of SMOF lipid compared to soybean lipid emulsion for extremely low birth weight (ELBW) premature infants. This was a prespecified secondary outcome analysis of a randomized trial of 230 infants (2012-2015).

It is recognized that the ELBW infants have very little nutritional reserve.  In addition, DHA which is transferred to the fetus in high amounts in the last trimester is absent from parenteral soybean lipid emulsions.  Thus, the authors explored whether SMOF lipid which is a mixture of lipids (30% soybean oil, 30% medium-chain triglycerides, 25% olive oil, and  15% fish oil) and contains DHA would have a favorable effect on neurocognitive outcomes.

In this study, the authors examined amplitude-integrated electroencephalography measurements (aEEG)  to assess neurodevelopment. Both groups received similar lipid dosing, SMOF 2.2 g/day and Soybean 2.1 g/day.

Key findings:

  • Among the available 121 infants in the subgroup with aEEG (n=63 SMOF, n=58 soybean), maximum maturational scores on aEEG were achieved 2 weeks earlier in the SMOF group (36.4 weeks vs 38.4 weeks, P<.001).

Limitation:

  • aEEG is a marker of neurocognitive development; however, more adequate outcomes of  neurodevelopmental progress are needed. The authors plan to follow these infants up to 5 years of age.

My take: This study is very favorable for the use of SMOF lipids in premature infants.  — SMOF lipid emulsion by itself may improve neurocognitive outcomes. In addition, clinicians are more likely to provide adequate amounts of lipid calories with SMOF as compared to soybean emulsion which is often restricted to minimize liver injury.  Giving adequate lipid calories is also likely to enhance neurological outcomes.

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Incredibly blue waters of Crater Lake, Oregon -from Wizard Island

 

Sclerosing Cholangitis-Like Changes Due to Drug Induced Liver Injury

A recent study (J Ahmad et al. Clin Gastroenterol Hepatol 2019; 17: 789-90) reviewed subjects in enrolled in drug-induced liver injury (DILI) prospective cohort to determine the frequency of sclerosing cholangitis (SC)-like changes in this population.  SC-like changes have previously been noted in up to 10% of DILI cases (Dig Liv dis 2015; 47: 502-7). In this study, 233 of 1487 subjects had underwent an MRI.

Key findings:

  • Four of 56 (7%) with adequate quality images had SC-like images (4 with intrahepatic stricture and 1 with a common hepatic duct stricture as well)
  • Patients with SC-like changes had a more severe initial injury noted and were more likely to develop chronic injury as noted by persistent lab abnormalities at 6 months

My take: This study indicates that a severe DILI can result in secondary sclerosing cholangitis.

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Dust Mites and Eosinophilic Esophagitis

Given seasonal fluctuation in the activity of eosinophilic esophagitis (EoE), aeroallergens have been considered a trigger in some patients.

Briefly noted: A recent study (A Ravi et al. Gastroenterol 2019; 157: 255-6, editorial 17) showed that dust mite antigen was present in esophageal biopsy specimens at a greater level in adult patients with EoE compared to controls.  With active EoE, patients had dust mite staining in 1.6% of the field which was significantly greater than patients with inactive EoE (0.7). The control group had a complete absence of epithelial dust mite staining.

The editorial (Seena Aceves) notes that these investigators have also shown gluten accumulation in the EoE esophagus.  Whether dust mite antigens or other specific postulated aeroallergens plays a causative role is unclear.  This study shows the presence of these antigens in the esophagus but does not show whether this is an epiphenomenon due to increased permeability or whether these antigens activate the local immune system.

A second study (T Patton et al. JPGN 2019; 69: e43-e48) describes the outcome of coexisting celiac disease and eosinophilic esophagitis in 22 children (from a cohort of 350 children with celiac disease. 17 had repeat biopsies.  Four of 17 (23.5%) had resolution of EoE with a gluten-free diet.  Related blog post: Is there a Link Between Eosinophilic Esophagitis and Celiac Disease?

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“Tofacitinib: A Jak of All Trades”

The clever title is derived from an editorial (KE Burke, AN Ananthakrishan. Clin Gastroenterol Hepatol 2019; 17: 1438-40) regarding three recent publications regarding Tofacitinib, a non-selective inhibitor of janus kinase (JAK) enzymes 1,2 and 3 which was FDA-approved in May 2018 for moderate to severe ulcerative colitis. This report was published prior to recent FDA warning regarding blood clots: FDA Warning on Tofacitinib

Two of the reports have been summarized previously on this blog:

The third study examines the safety of tofacitinib: W Sandborn et al. Clin Gastroenterol Hepatol 2019; 17: 1541-50

Methods: This study analyzed data from phase 2 and phase 3 trials with 1157 patients who had a median treatment of 1.4 years (1613 person-years).  More than three-fourths were receiving 10 mg BID.

Findings:

  • Serious infections were infrequent but there was a dose response relationship associated with herpes zoster infections.  At 10 mg BID,  the frequency was 5% whereas the rate was 1.5% in those receiving 5 mg BID and 0.5% in placebo-treated patients. This is likely related to interference of interferon production related to JAK inhibitor disruption.
  • Sandborn et al conclude that the “safety profile of tofacitinib for patients with UC appeared similar to that reported for patients with rheumatoid arthritis and for patients with UC treated with biologic agents, except for the higher incidence rate of herpes zoster infection.”

The editorial recommends NOT using tofacitinib for acute severe ulcerative colitis (ASUC); it “should be encouraged only in selected patients and preferably in the context of a research study.”  “Infliximab and cyclosporine [should be used] for steroid refractory UC;” however, they suggest that “one can consider initiating tofacitinib PRIOR to patients becoming steroid refractory.  “It could be used upfront on day 1.”

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Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications/diets (along with potential adverse effects) should be confirmed by prescribing physician/nutritionist.  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.

Should Pediatric Patients with Celiac Disease Be Screened for Low Bone Mineral Density?

A recent retrospective study (J Webster et al. Clin Gastroenterol Hepatol 2019; 17: 1509-14) with 673 children with newly diagnosed (biopsy-proven) celiac disease (CD) (median age 10.6 y) evaluated DXA studies at time of diagnosis.

Key findings:

  • Approximately 7% (n=46) had a low lumbar spine areal bone mineral density (aBMD) z-score (less than -2)
  • Of those with abnormal aBMDs, 18 had repeat studies.  11 of 18 normalized after institution of dietary management. Mean time for repeat DXA was 2.3 years
  • Of note, mean BMI z-score at time of repeat DXA was 0.005 (this includes 90 who had followup studies after a normal baseline DXA).
  • Low body mass index (BMI) with z-score of -0.4 identified a >10% risk of an abnormal aBMD

The authors acknowledge than DXA screening is controversial.  The current study’s strength is its large size.  Limitations include the inability to correlate with clinical factors including adherence to a gluten-free diet.

My take:

  1. Based on this study, it is likely that only 2-3% of pediatric patients with celiac disease will have a persistently abnormal DXA after institution of a gluten free diet for 2 years; it is likely that even more will improve with time if receiving appropriate dietary treatment.
  2. I am not likely to recommend obtaining a baseline DXA study in pediatric patients with newly diagnosed celiac disease; the treatment for low bone mineral density in the setting of celiac disease is the same as for all children with celiac disease.  If one were inclined to look for low BMD, optimal timing would likely be AFTER being adherent on a gluten free diet for at least two years particularly in those who had low BMI at presentation.

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Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications/diets (along with potential adverse effects) should be confirmed by prescribing physician/nutritionist.  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