Quantitative magnetic resonance imaging assessment of muscle composition in myotonic dystrophy mice.

Myotonic dystrophy type 1 (DM1) is a severe autosomal dominant neuromuscular disease in which the musculoskeletal system contributes substantially to overall mortality and morbidity. DM1 stems from a noncoding CTG trinucleotide repeat expansion in the DMPK gene. The human skeletal actin long repeat (HSALR) mouse model reproduces several aspects of the disease, but the muscle-wasting phenotype of this model has never been characterized in vivo. Herein, we used quantitative MRI to measure the fat and muscle volumes in the leg compartment (LC) of mice. These acquired data were processed to extract relevant parameters such as fat fraction and fat infiltration (fat LC/LC) in HSALR and control (FBV) muscles. These results showed increased fat volume (fat LC) and fat infiltration within the muscle tissue of the leg compartment (muscle LC), in agreement with necropsies, in which fatty clumps were observed, and consistent with previous findings in DM1 patients. Model mice did not reproduce the characteristic impaired fat fraction, widespread fat replacement through the muscles, or reduced muscle volume reported in patients. Taken together, the observed abnormal replacement of skeletal muscle by fat in the HSALR mice indicates that these mice partially reproduced the muscle phenotype observed in humans.

Vortical features for myocardial rotation assessment in hypertrophic cardiomyopathy using cardiac tagged magnetic resonance.

Left ventricular rotational motion is a feature of normal and diseased cardiac function. However, classical torsion and twist measures rely on the definition of a rotational axis which may not exist. This paper reviews global and local rotation descriptors of myocardial motion and introduces new curl-based (vortical) features built from tensorial magnitudes, intended to provide better comprehension about fibrotic tissue characteristics mechanical properties. Fifty-six cardiomyopathy patients and twenty-two healthy volunteers have been studied using tagged magnetic resonance by means of harmonic phase analysis. Rotation descriptors are built, with no assumption about a regular geometrical model, from different approaches. The extracted vortical features have been tested by means of a sequential cardiomyopathy classification procedure; they have proven useful for the regional characterization of the left ventricular function by showing great separability not only between pathologic and healthy patients but also, and specifically, between heterogeneous phenotypes within cardiomyopathies.

Assessment of Targeted Next-Generation Sequencing as a Tool for the Diagnosis of Charcot-Marie-Tooth Disease and Hereditary Motor Neuropathy.

Charcot-Marie-Tooth disease is characterized by broad genetic heterogeneity with >50 known disease-associated genes. Mutations in some of these genes can cause a pure motor form of hereditary motor neuropathy, the genetics of which are poorly characterized. We designed a panel comprising 56 genes associated with Charcot-Marie-Tooth disease/hereditary motor neuropathy. We validated this diagnostic tool by first testing 11 patients with pathological mutations. A cohort of 33 affected subjects was selected for this study. The DNAJB2 c.352+1G>A mutation was detected in two cases; novel changes and/or variants with low frequency (<1%) were found in 12 cases. There were no candidate variants in 18 cases, and amplification failed for one sample. The DNAJB2 c.352+1G>A mutation was also detected in three additional families. On haplotype analysis, all of the patients from these five families shared the same haplotype; therefore, the DNAJB2 c.352+1G>A mutation may be a founder event. Our gene panel allowed us to perform a very rapid and cost-effective screening of genes involved in Charcot-Marie-Tooth disease/hereditary motor neuropathy. Our diagnostic strategy was robust in terms of both coverage and read depth for all of the genes and patient samples. These findings demonstrate the difficulty in achieving a definitive molecular diagnosis because of the complexity of interpreting new variants and the genetic heterogeneity that is associated with these neuropathies.

Internal and external validation of a model to predict adverse outcomes in patients with left-sided infective endocarditis.

INTRODUCTION: Early identification of prognostic factors is essential to improve the grim prognosis associated with left-sided infective endocarditis. This group identified three independent risk factors obtained within 72 h of admission, (Staphylococcus aureus, heart failure and periannular complications) for inhospital mortality or urgent surgery in a series of 317 patients diagnosed at five tertiary centres (derivation sample). A stratification score was constructed for the test cohort by a simple arithmetic sum of the number of variables present. The goal was to validate this model internally and externally in a prospective manner with two different cohorts of patients. METHODS: The appropriateness of the model was tested prospectively on predicting events in two cohorts of patients with left-sided endocarditis: internally with the 263 consecutive patients diagnosed at the same centres where the model was derived (internal validation sample), and externally with 264 patients admitted at another hospital (external validation sample). RESULTS: The discriminatory power of the model, expressed as the area under the receiver operating characteristic curve was similar between derivation and both validation samples (internal 0.67 vs 0.68, p=0.79; external 0.67 vs p=0.74, p=0.09). There was a progressive, significant pattern of increasing event rates as the risk stratification score increased in both validation cohorts (p<0.001 by χ² for trend). CONCLUSIONS: The early risk stratification model derived, based on variables obtained within 72 h of admission, is applicable to different populations with left-sided endocarditis. A simple bedside assessment tool is provided to clinicians that identifies patients at high risk of having an adverse event.