Carotid Intima-Media Thickness and Carotid Plaques Improves Prediction of Obstructive Angiographic Coronary Artery Disease in Women

Does carotid intima-media thickness (cIMT), a surrogate marker of cardiovascular events, have predictive incremental value over established risk factors for stable coronary artery disease (CAD)? Prospective study of 300 patients, with suspected stable CAD, admitted for an elective coronary angiography and carotid ultrasound. The CAD patients had a higher cIMT, which showed a modest predictive accuracy for CAD (area under the receiver-operating characteristic curve 0.638, 95% confidence interval 0.576-0.701, P < .001). The cIMT was an independent predictor of CAD, together with age, gender, and diabetes. C-statistic for CAD prediction by traditional risk factors was not significantly different from a model that included cIMT, carotid plaque presence, or both. However, in women, it was significantly increased by the addition of cIMT or carotid plaque presence. Although cIMT cannot be used as a sole indicator of CAD, it should be considered in the panel of investigations that is requested, particularly in women who are candidates for coronary angiography.

Leber Congenital Amaurosis: Comprehensive Survey of the Genetic Heterogeneity, Refinement of the Clinical Definition, and Genotype-Phenotype Correlations as a Strategy for Molecular Diagnosis

Leber congenital amaurosis (LCA) is the earliest and most severe form of all inherited retinal dystrophies, responsible for congenital blindness. Disease-associated mutations have been hitherto reported in seven genes. These genes are all expressed preferentially in the photoreceptor cells or the retinal pigment epithelium but they are involved in strikingly different physiologic pathways resulting in an unforeseeable physiopathologic variety. This wide genetic and physiologic heterogeneity that could largely increase in the coming years, hinders the molecular diagnosis in LCA patients. The genotyping is, however, required to establish genetically defined subgroups of patients ready for therapy. Here, we report a comprehensive mutational analysis of the all known genes in 179 unrelated LCA patients, including 52 familial and 127 sporadic (27/127 consanguineous) cases. Mutations were identified in 47.5% patients. GUCY2D appeared to account for most LCA cases of our series (21.2%), followed by CRB1 (10%), RPE65 (6.1%), RPGRIP1 (4.5%), AIPL1 (3.4%), TULP1 (1.7%), and CRX (0.6%). The clinical history of all patients with mutations was carefully revisited to search for phenotype variations. Sound genotype-phenotype correlations were found that allowed us to divide patients into two main groups. The first one includes patients whose symptoms fit the traditional definition of LCA, i.e., congenital or very early cone-rod dystrophy, while the second group gathers patients affected with severe yet progressive rod-cone dystrophy. Besides, objective ophthalmologic data allowed us to subdivide each group into two subtypes. Based on these findings, we have drawn decisional flowcharts directing the molecular analysis of LCA genes in a given case. These flowcharts will hopefully lighten the heavy task of genotyping new patients but only if one has access to the most precise clinical history since birth.

Acute Otitis Media a Reliable Warning Sign for Primary Immunodeficiencies?- A Critical Appraisal

Acute otitis media (AOM) is the most common infection in childhood, resulting from both anatomic and immunologic specificities of this age group. Recurrent AOM has been defined as one of the warning signs for primary immunodeficiencies (PID), In this study we evaluated the strength of recurrent AOM as clinical predictor of PID. Methods: Retrospective study (August 2010 - December 2013) which included all patients referred to PID appointment because of recurrent AOM (= 8 AOM episodes/year). Syndromic patients or those presenting with another warning sign for PID were excluded. Clinical, demographic and laboratory results were analized and statistical analysis was made using SPSS 20. Results: Seventy-five patients were included (median age 37,8 months; 62,7% male gender), corresponding to 15% of all first appointments. Other comorbidities were present in 20% of the patients and 17% had ORL surgery prior to PID referral. In most patients, the immunologic screening consisted on the evaluation of humoral function, but in selected cases other studies were performed (namely complement and lymphocyte immunophenotyping). A PID was identified in 12 children (16,0%) and the majority of these patients had other distinctive feature (personal or familiar antecedent of infection or auto-immunity, 66,7%, p<0,05). Nine children (12,0%) underwent prophylactic cotrimoxazole. The average length of follow-up was 11,2 months. Conclusion: Despite being a very frequent cause of immunologic screening, in this study recurrent AOM was not found to be a good predictor of underlying PID, unless the patients presents other significant personal or family history.