Individual-specific levels of CTG•CAG somatic instability are shared across multiple tissues in myotonic dystrophy type 1.

Myotonic dystrophy type 1 is a complex disease caused by a genetically unstable CTG repeat expansion in the 3'-untranslated region of the DMPK gene. Age-dependent, tissue-specific somatic instability has confounded genotype-phenotype associations, but growing evidence suggests that it also contributes directly toward disease progression. Using a well-characterized clinical cohort of DM1 patients from Costa Rica, we quantified somatic instability in blood, buccal cells, skin and skeletal muscle. Whilst skeletal muscle showed the largest expansions, modal allele lengths in skin were also very large and frequently exceeded 2000 CTG repeats. Similarly, the degree of somatic expansion in blood, muscle and skin were associated with each other. Notably, we found that the degree of somatic expansion in skin was highly predictive of that in skeletal muscle. More importantly, we established that individuals whose repeat expanded more rapidly than expected in one tissue (after correction for progenitor allele length and age) also expanded more rapidly than expected in other tissues. We also provide evidence suggesting that individuals in whom the repeat expanded more rapidly than expected in skeletal muscle have an earlier age at onset than expected (after correction for the progenitor allele length). Pyrosequencing analyses of the genomic DNA flanking the CTG repeat revealed that the degree of methylation in muscle was well predicted by the muscle modal allele length and age, but that neither methylation of the flanking DNA nor levels of DMPK sense and anti-sense transcripts could obviously explain individual- or tissue-specific patterns of somatic instability.

Sex Differences Among Participants in the Latin American Stroke Registry.

Background Reports on sex differences in stroke outcome and risk factors are scarce in Latin America. Our objective was to analyze clinical and prognostic differences according to sex among participants in the LASE (Latin American Stroke Registry). Methods and Results Nineteen centers across Central and South America compiled data on demographics, vascular risk factors, clinical stroke description, ancillary tests, and functional outcomes at short-term follow-up of patients included from January 2012 to January 2017. For the present study, all these variables were analyzed according to sex at hospital discharge. We included 4788 patients with a median in-hospital stay of 8 days (interquartile range, 5-8); 2677 were male (median age, 66 years) and 2111 female (median age, 60 years). Ischemic stroke occurred in 4293: 3686 as cerebral infarction (77%) and 607 as transient ischemic attack cases (12.7%); 495 patients (10.3%) corresponded to intracerebral hemorrhage. Poor functional outcome (modified Rankin scale, 3-6) was present in 1662 (34.7%) patients and 38.2% of women (P<0.001). Mortality was present in 6.8% of the registry, with 7.8% in women compared with 6.0% in men (P=0.01). Death and poor functional outcome for all-type stroke showed a higher risk in female patients (hazard ratio, 1.3, P=0.03; and hazard ratio, 1.1, P=0.001, respectively). Conclusions A worse functional outcome and higher mortality rates occurred in women compared with men in the LASE, confirming sex differences issues at short-term follow-up.

Safety of Dual Antiplatelet Therapy After Carotid Endarterectomy for Prevention of Restenosis: A Single Center Experience.

INTRODUCTION: The incidence of recurrent carotid stenosis after carotid endarterectomy varies from 1% to 37% with only 0-8% symptomatic restenosis. Safety of short-term (30 days) dual-antiplatelet therapy has not been established in this type of procedure. AIMS: To investigate the safety of dual antiplatelet therapy after carotid endarterectomy to prevent restenosis. METHODS: We retrospectively identified all the patients who underwent carotid endarterectomy (symptomatic or asymptomatic) treated at our center between July 2010 and July 2013 according to local protocols. All patients received a dose of 100 mg of aspirin daily immediately after carotid endarterectomy, with subsequent 100 mg of aspirin daily for the rest of the study period, and some patients received 75 mg of Clopidogrel for 30 days starting immediately after surgical procedure (dual therapy group), assigned according to medical criteria. Duplex carotid ultrasound and clinical assessments were performed at 30 days and 1 year after the procedure. RESULTS: A total of 44 patients (71.2 ± 7.9 years old; 77.2% symptomatic) were analyzed; 35 of them with dual therapy (79.54%). At 30 days, two patients from the mono-therapy group developed restenosis (22.2%), compared to none in dual therapy group (p=0.04). At one year follow-up, only one patient from the dual group showed restenosis (p=0.10). No deaths, major bleeding or new strokes were reported in both groups. CONCLUSIONS: Short-term dual antiplatelet therapy with aspirin and clopidogrel after carotid endarterectomy might be associated with a lower incidence of restenosis. This observation must be validated in a prospective trial.