Triheptanoin versus trioctanoin for long-chain fatty acid oxidation disorders: a double blinded,randomized controlled trial

Background

Observational reports suggest that supplementation that increases citric acid cycle intermediates via anaplerosis may have therapeutic advantages over traditional medium-chain triglyceride (MCT) treatment of long-chain fatty acid oxidation disorders (LC-FAODs) but controlled trials have not been reported. The goal of our study was to compare the effects of triheptanoin (C7), an anaplerotic seven-carbon fatty acid triglyceride, to trioctanoin (C8), an eight-carbon fatty acid triglyceride, in patients with LC-FAODs.

Methods

A double blinded, randomized controlled trial of 32 subjects with LC-FAODs (carnitine palmitoyltransferase-2, very long-chain acylCoA dehydrogenase, trifunctional protein or long-chain 3-hydroxy acylCoA dehydrogenase deficiencies) who were randomly assigned a diet containing 20% of their total daily energy from either C7 or C8 for 4 months was conducted. Primary outcomes included changes in total energy expenditure (TEE), cardiac function by echocardiogram, exercise tolerance, and phosphocreatine recovery following acute exercise. Secondary outcomes included body composition, blood biomarkers, and adverse events, including incidence of rhabdomyolysis.

Results

Patients in the C7 group increased left ventricular (LV) ejection fraction by 7.4% (p = 0.046) while experiencing a 20% (p = 0.041) decrease in LV wall mass on their resting echocardiogram. They also required a lower heart rate for the same amount of work during a moderate-intensity exercise stress test when compared to patients taking C8. There was no difference in TEE, phosphocreatine recovery, body composition, incidence of rhabdomyolysis, or any secondary outcome measures between the groups.

Conclusions

C7 improved LV ejection fraction and reduced LV mass at rest, as well as lowering heart rate during exercise among patients with LC-FAODs.Clinical Trial Registration: Clinicaltrials.gov NCT01379625.

     

Incorporation of a Formalized Emergency Radiology Curriculum to Facilitate Population of a MIRC-based Digital Teaching File

Teaching files are integral to radiological training. Digital Imaging and Communication in Medicine compatible digital radiological data and technological advances have made digital teaching files a desirable way to preserve and share representative and/or unusual cases for training purposes. The Medical Imaging Resource Community (MIRC) system developed by the Radiological Society of North America (RSNA) is a robust multi-platform digital teaching file implementation that is freely available. An emergency radiology training curriculum developed by the American Society of Emergency Radiology (ASER) was incorporated to determine if such an approach might facilitate the entry, maintenance, and cataloguing of interesting cases. The RSNA MIRC software was obtained from the main MIRC website and installed. A coding system was developed based on the outline form of the ASER curriculum. Weekly reports were generated tallying the number of cases in each category of the curriculum. Resident participation in the entry and maintenance of cases markedly increased after incorporation of the ASER curriculum. The coding schema facilitated progress assessment. Ultimately, 454 total cases were entered into the MIRC database, representing at least 42% of the subcategories within the ASER curriculum (161 out of 376). The incorporation of the ASER emergency radiology curriculum greatly facilitated the location, cataloguing, tracking, and maintenance of representative cases and served as an effective means by which to unify the efforts of the department to develop a comprehensive teaching resource within this subspecialty. This approach and format will be extended to other educational curricula in other radiological subspecialties.     

Heterogeneous phenotypes of platelet and plasma von Willebrand factor in obligatory heterozygotes for severe von Willebrand disease

To characterize the heterogeneity of severe (type III) von Willebrand disease (vWD), plasma and platelet von Willebrand factor antigen (vWF:Ag) and ristocetin cofactor activity (Ricof) were measured in 28 obligatory heterozygotes (ie, parents or children of probands from 15 different kindreds with severe vWD). On the average, heterozygotes had low levels of vWF in both platelets and plasma. There was, however, considerable heterogeneity, with four distinct patterns. Eleven heterozygotes had concordant reduction of vWF:Ag and Ricof in both plasma and platelets; five had low levels of vWF:Ag and Ricof in plasma contrasting with normal levels in platelets; eight had a peculiar pattern, the reverse of the above (ie, low levels in platelets and normal levels in plasma); and in one, both vWF measurements were normal in plasma and platelets. These patterns were genetically determined: they were consistent in four couples of consanguineous heterozygotes and in two couples carrying the same gene deletion. Only the remaining three heterozygotes had no clearly identifiable pattern. Other findings of this study were that although most of the heterozygotes had normal bleeding times, the 7 of 28 who had prolonged bleeding times had concordantly low levels of vWF measurements in both plasma and platelets. In conclusion, this large series of obligatory heterozygotes provides evidence for phenotypic and genotypic heterogeneity of severe vWD.     

Characterization of antibody and selection of alternative drug therapy in hydrochlorothiazide-induced immune hemolytic anemia

The authors report the clinical and laboratory findings of a patient who had severe immune hemolytic anemia due to hydrochlorothiazide (HCTZ). In this case, the HCTZ antibody reacted not only with other thiazide and thiazide-like drugs, but also with a chemically unrelated diuretic, ethacrynic acid. These results indicate that HCTZ antibody activity is not restricted solely to the thiazides and imply that therapy with any of the reactive drugs would be contraindicated for this patient. The serologic screening for drug reactivity may be useful for selecting alternative therapy for patients with drug-induced immune hemolytic anemia.