Preanalytical errors in emergency department samples: Investigating error sources.

BACKGROUND: The presence of preanalytical errors is a recurring fact in all areas of healthcare that send samples to laboratories. Increasing the knowledge of possible sources of error in the preanalytical phase has been the objective of this group during the last 10 years. METHODS: In this study, descriptive research has been carried out using professionals' opinions obtained by means of the Strengths, Weaknesses, Opportunities, and Threats method in a focus group. RESULTS: The opinions expressed within the focus group have emphasised the importance of patients' safety and willingness for the introduction of a computerized analytical module. The most commented weakness in both hospitals was the transport of samples through the pneumatic tube. Improving the duration of workers' contracts, especially in the laboratory, and creating a circuit for professional's localization during the work shift to facilitate potential error solving are some opportunities for the future. CONCLUSIONS: Different approaches have been developed depending on the healthcare scenario. For this, establishing a flow of information between the different professionals allows identifying identical aspects through a priori, different points of view. The line to follow is to improve the safety of the patient and also to give professionals an opportunity to express themselves.

Assessment of Collateral Circulation Using Perfusion CT in Middle Cerebral Artery Thrombectomy-Treated Patients.

INTRODUCTION: The prognostic value of leptomeningeal collateral circulation in thrombectomy-treated patients remains unclear. We evaluated the construct validity of assessing leptomeningeal collateral circulation using a new regional perfusion CT source image-based approach, the Perfusion Acquisition for THrombectomy Scale (PATHS). We also compared the prognostic value of PATHS with a further 6 scales based on various techniques: CT-angiography, perfusion CT, and digital subtraction angiography. Additionally, we studied the relationship between the scores for the different scales. PATIENTS AND METHODS: We performed a retrospective study of consecutive patients with stroke and M1/terminal carotid occlusion treated with thrombectomy in our center. Leptomeningeal collateral circulation was prospectively evaluated using 7 scales: Tan and Miteff (CT Angiography); Calleja, Cao, American Society of Intervention and Therapeutic Neuroradiology/Society of Interventional Radiology, and PATHS (perfusion); and Christoforidis (Digital Subtraction Angiography). Correlations were studied using the Spearman method. RESULTS: The study population comprised 108 patients. All scales predicted the modified Rankin Scale at 3 months (P ≤ .02) and all but 1 (Christoforidis) correlated with 24-hour brain infarct volume (P ≤ .02). These correlations were higher with PATHS (rho = -0.47, P < .001 for 3-month modified Rankin Scale; rho = -0.35, P < .001 for follow-up infarct volume). The multivariate analysis showed PATHS to be an independent predictor of modified Rankin Scale at 3 months less than equal to 2. A crosscorrelation analysis revealed a better correlation between scales that used the same techniques. CONCLUSIONS: PATHS can be used to assess leptomeningeal collateral circulation. PATHS had better prognostic value than other scales; therefore, it might be considered for assessment of leptomeningeal collateral circulation in candidates for thrombectomy. The moderate correlation between scales suggests that scores are not interchangeable.

Estudio mutacional de EGFR y PIK3CA y de hipermetilación del promotor del gen BRCA1 en cáncer de mama tipo «triple negativo» / Study of the EGFR and PIK3CA mutations and BRCA1 promoter hypermethylation in «triple-negative» breast cancer

Introducción. El cáncer de mama es una enfermedad muy heterogénea a nivel clínico, morfológico y biológico, que se clasifica en diferentes subgrupos. El tipo «triple negativo» representa el 10-20% de todos los cánceres de mama, frecuentemente muestra expresión de marcadores basales, afecta a mujeres jóvenes y tiene mal pronóstico, sin una terapia dirigida. Material y método. Estudio retrospectivo de análisis de tres alteraciones moleculares (mutación de EGFR y PIK3CA e hipermetilación del promotor del gen BRCA1), mediante la técnica de pirosecuenciación, en 60 casos de cáncer de mama «triple negativo». Resultados. Un 28,33% de las pacientes fueron diagnosticadas con 50 o menos años, y el 16,67% progresaron por diseminación vía hematógena con metástasis viscerales y murieron (menos una) en un intervalo de entre 1-5 años desde el diagnóstico. En 5 de los 16 casos estudiados se encontró una mutación patogénica de BRCA. Inmunohistoquímicamente la mayoría eran tumores con alto índice proliferativo de Ki67 y un 73,33% eran «basal-like» por expresión de CK5/6 y/o EGFR. A nivel molecular, no se encontraron mutaciones activadoras de EGFR, aunque el 53,33% de los casos mostraron sobreexpresión inmunohistoquímica de EGFR. La mutación de PIK3CA se detectó en un 10% de casos, con predominio en exón20 y con coexpresión de receptores de andrógenos en la mitad de los casos. La hipermetilación de la región promotora del gen BRCA1 estaba presente en un 25% de los casos, coexistiendo en un caso con hipermetilación del estroma no tumoral y en dos con mutación patogénica del gen BRCA1. Conclusiones. El hallazgo de alguna alteración molecular específica, aunque sea infrecuente, puede plantear una posible diana terapéutica dirigida (AU)

Introduction. Breast cancer is a clinically, morphologically and biologically heterogeneous disease. It is classified in distinct subtypes. Triple-negative breast cancers represent approximately 10-20% of all breast cancers and often express basal markers. This type preferentially affects young women and has no specific therapy. Material and method. We conducted a retrospective study of three molecular alterations (the EGFR and PIK3CA mutations and BRCA1 promoter hypermethylation) by pyrosequencing in a series of 60 patients with a diagnosis of triple-negative breast cancer. Results. A total of 28.33% of patients were diagnosed at age 50 years or younger. Only 16.67% of patients had clinical progression due to haematological dissemination with visceral metastasis and all of them, except one, died from breast cancer between 1 and 5 years after diagnosis. The BRCA1 mutation was studied in 16 patients and a known pathogenic mutation was found in 5. Immunohistochemical study showed a high Ki67 proliferative index and 73.33% of carcinomas were basal-like due to CK5/6 and/or EGFR expression. Although we found no EGFR-activating mutations, EGFR overexpression was present in 53.33% of patients. The PIK3CA mutation was identified in 10% of patients, predominantly in exon 20 and with androgen receptor expression in half of these patients. BRCA1 promoter hypermethylation was observed in 25% of the patients. Only one of these patients exhibited BRCA1 hypermethylation of non-tumoural stroma and two showed a pathogenic mutation of the BRCA1 gene. Conclusion. The finding of specific molecular alterations, although infrequent, could suggest a possible directed therapeutic target (AU)

Polymorphism in genes involved in adrenergic signaling associated with Alzheimer's.

To investigate the potential involvement of adrenergic signaling in Alzheimer's disease (AD) pathogenesis, we performed genetic and functional studies of genes initiating the cascade. We chose two functional single-nucleotide polymorphisms (SNPs) in the beta1-adrenergic receptor (ADRB1) and the G protein beta3 subunit (GNB3) genes, respectively, and analyzed their allelic frequencies in a case-control sample of AD. We found that the GNB3 T allele produces a significant risk for AD in individuals homozygous for the ADRB1 C allele, suggesting that the combined effect of both polymorphisms influences AD susceptibility. Interestingly, the co-expression of GNB3 T and ADRB1 C alleles, compared with GNB3 C and ADRB1 G, produced increased cAMP levels and MAPK activation following adrenergic stimulation of transfected human cell lines. Furthermore, the co-expression of these alleles also produced increases in APP expression. These data strongly indicate that the combination of GNB3 and ADRB1 polymorphisms produces AD susceptibility by changing the cell responsiveness to adrenergic stimulation, pointing to the modulation of brain adrenergic receptors as a potential target for novel AD therapeutic strategies.