Oral anticoagulation and left atrial appendage closure: a new strategy for recurrent cardioembolic stroke.

BACKGROUND AND PURPOSE: There are no recommendations regarding how to treat cardioembolic recurrent strokes when patients are well anticoagulated. We evaluated the safety and efficacy of combining oral anticoagulation (OAC) with percutaneous left atrial appendage closure (LAAC) in patients with well-anticoagulated atrial fibrillation (AF) with recurrent strokes. METHODS: In an explorative, prospective, observational study, LAAC was performed in patients with AF with at least two ischaemic strokes in the previous year, despite good anticoagulation using the Amplatzer Cardiac Plug (St Jude Medical, St Paul, MN, USA) or Amulet Abbot device (Abbot Vascular, Santa Clara, CA, USA). We recorded age, type of AF, CHA2 DS2 -VASC and HAS-BLED scores, types of OAC and risk factors. After closure, treatment with aspirin (100 mg/day) was continued for 3 months in combination with indefinite OAC. Clinical status, recurrent embolisms and bleeding complications were recorded during follow-up. RESULTS: A total of 19 patients were included (mean age, 72.1 ± 9.6 years; mean CHA2 DS2 -VASC score, 5.3 ± 1.48; mean number of previous strokes, 2.78 ± 1.15). Thirteen had spontaneous echocardiographic contrast and all had dilatation of the left atrium. Eighteen patients had a multilobulated left atrial appendage, 17 with 'chicken-wing' morphology and one patient had a left atrial appendage thrombus. There were no complications during the procedure. Only one patient had a transient ischaemic attack and no major bleeding occurred during a mean follow-up of 17.4 ± 11.5 months. CONCLUSION: Combination therapy with indefinite OAC plus LAAC in patients with AF with recurrent strokes despite good anticoagulation should be considered in order to prevent a new stroke.

[Experimental models used in research into genetic disorders that involve intellectual disability]. / Modelos experimentales utilizados en la investigación de trastornos genéticos que cursan con discapacidad intelectual.

INTRODUCTION: A basic principle of molecular and clinical medicine states that the function of the organs and the cells they are made up of is determined by the overall set of specific proteins. Therefore, the function of each organ depends on the molecules present in each cell, and hence it comes as no surprise to find that when tissue function is altered, different changes have taken place in the proteins. In the nervous system there are numerous examples of changes in proteins that correlate with functional alterations, either during normal or pathological development. DEVELOPMENT: In order to understand these relations, and to establish models in which to study the aetiopathogenesis of the disease, it is necessary to direct steady synthesis or to suppress synthesis in the brain of the protein that is potentially involved in the development of the disease. In consequence, it is possible to determine whether the presence or the absence of the protein is the direct or indirect cause of the effects; this is one of the main goals that must be achieved in order to enable researchers to define potential therapeutic targets in hereditary diseases. In order to manipulate the specific protein causing a pathology, we use experimental animal models as essential research tools, since they enable us to determine which mechanisms are altered and how the function of a particular protein affects the mechanisms being studied. CONCLUSIONS: Suppressing a gene or its over-expression in models using genetically modified mice will provide us with a means of modifying the genome and, eventually, the protein in the different tissues as well as in the nervous system in an attempt to imitate the genetic pathology that involves mental retardation. By controlling or suppressing the expression of a protein in the brain it becomes possible to remodel the functional profile of the tissue and study the consequences of molecular genetic manipulation, together with the biochemical, cytological and physiological processes, under normal basal conditions and under specific stimuli or conditions such as stress.