Analysis of SLX4/FANCP in non-BRCA1/2-mutated breast cancer families

<p>Abstract</p> <p>Background</p> <p>Genes that, when mutated, cause Fanconi anemia or greatly increase breast cancer risk encode for proteins that converge on a homology-directed DNA damage repair process. Mutations in the <it>SLX4 </it>gene, which encodes for a scaffold protein involved in the repair of interstrand cross-links, have recently been identified in unclassified Fanconi anemia patients. A mutation analysis of <it>SLX4 </it>in German or Byelorussian familial cases of breast cancer without detected mutations in <it>BRCA1 </it>or <it>BRCA2 </it>has been completed, with globally negative results.</p> <p>Methods</p> <p>The genomic region of <it>SLX4</it>, comprising all exons and exon-intron boundaries, was sequenced in 94 Spanish familial breast cancer cases that match a criterion indicating the potential presence of a highly-penetrant germline mutation, following exclusion of <it>BRCA1 </it>or <it>BRCA2 </it>mutations.</p> <p>Results</p> <p>This mutational analysis revealed extensive genetic variation of <it>SLX4</it>, with 21 novel single nucleotide variants; however, none could be linked to a clear alteration of the protein function. Nonetheless, genotyping 10 variants (nine novel, all missense amino acid changes) in a set of controls (138 women and 146 men) did not detect seven of them.</p> <p>Conclusions</p> <p>Overall, while the results of this study do not identify clearly pathogenic mutations of <it>SLX4 </it>contributing to breast cancer risk, further genetic analysis, combined with functional assays of the identified rare variants, may be warranted to conclusively assess the potential link with the disease.</p

The management of acute venous thromboembolism in clinical practice. Results from the European PREFER in VTE Registry

Venous thromboembolism (VTE) is a significant cause of morbidity and mortality in Europe. Data from real-world registries are necessary, as clinical trials do not represent the full spectrum of VTE patients seen in clinical practice. We aimed to document the epidemiology, management and outcomes of VTE using data from a large, observational database. PREFER in VTE was an international, non-interventional disease registry conducted between January 2013 and July 2015 in primary and secondary care across seven European countries. Consecutive patients with acute VTE were documented and followed up over 12 months. PREFER in VTE included 3,455 patients with a mean age of 60.8 ± 17.0 years. Overall, 53.0 % were male. The majority of patients were assessed in the hospital setting as inpatients or outpatients (78.5 %). The diagnosis was deep-vein thrombosis (DVT) in 59.5 % and pulmonary embolism (PE) in 40.5 %. The most common comorbidities were the various types of cardiovascular disease (excluding hypertension; 45.5 %), hypertension (42.3 %) and dyslipidaemia (21.1 %). Following the index VTE, a large proportion of patients received initial therapy with heparin (73.2 %), almost half received a vitamin K antagonist (48.7 %) and nearly a quarter received a DOAC (24.5 %). Almost a quarter of all presentations were for recurrent VTE, with &gt;80 % of previous episodes having occurred more than 12 months prior to baseline. In conclusion, PREFER in VTE has provided contemporary insights into VTE patients and their real-world management, including their baseline characteristics, risk factors, disease history, symptoms and signs, initial therapy and outcomes

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

Aspectos actuales de la organogénesis. Función e involución del timo

El timo es un órgano linfoide central o primario localizado en la parte anterosuperior del tórax. Constituye el principal sitio de diferenciación y maduración de las células T. En esta revisión se detallan aspectos actuales de la embriología, la histología y la función tímica y en la generación de los diferentes subtipos de timocitos y su diferenciación a células T maduras efectoras, la inducción de las células T tímicas reguladoras involucradas en el mantenimiento de la tolerancia a lo propio y la involución que sufre este órgano durante el proceso de inmunosenescencia

Linfomas cutáneos: Aspectos relevantes Cutaneous lynphomas: Significant aspects

Los linfomas cutáneos constituyen un amplio grupo dentro de los linfomas no hodgkinianos. Incluyen varios tipos de desórdenes linfoproliferativos y se clasifican según su origen en T ó B, cuadro clínico y morfología. Dentro de estos se encuentran la micosis fungoides y el síndrome de Sézary, que son entidades que aunque difieren en sus manifestaciones clínicas, se cree que son variantes de un mismo trastorno linfoproliferativo del linfocito T CD4. Estos linfomas no hodgkinianos de células T aparecen entre los 40 y 60 años y es 2,2 veces más frecuente en el sexo masculino que en el femenino. Un adecuado tratamiento depende de un exacto diagnóstico morfológico, inmunológico, genético y molecular que permitiría una más rápida remisión, una mayor sobrevida y la incorporación de estos individuos a la vida útil de la sociedad.The cutaneous lymphomas constitute a large group within the non-Hodgkin lymphomas. They include various types of lymphoproliferative disorders and they are classified according to their origin, clinical picture and morphology in T or B. The fungoid mycosis and Sézary's syndrome are among them. Although these entities differ in their clinical manifestations, it is believed that they are variants of a same lymphoproliferative disorder of the CD4 T-lymphocyte. These non-Hodgkin lymphomas of T-cells appear in individuals aged 40-60 and they are two times more frequent in males than in females. An adequate treatment depends on an accurate morphological, immunological, genetic and molecular diagnosis that will allow a faster remission, a higher survival and the incorporation of these individuals to society's useful life

Aplicación del método inmunocitoquímico de la fosfatasa alcalina anti-fosfatasa alcalina para la clasificación inmunológica de las leucemias mieloides agudas Application of the alkaline phosphatase anti-alkaline phosphatase immunocytochemical method for the immunological classification of acute myeloid leukemias

Se realizó el inmunofenotipaje celular de 30 pacientes con el diagnóstico de leucemia mieloide aguda por el método inmunocitoquímico fosfatasa alcalina anti-fosfatasa alcalina (APAAP) introducido en nuestro laboratorio. Los marcadores estudiados fueron: CD3, CD13, CD15, CD19, CD33 y CD41. Para el estudio se utilizaron extendidos de médula ósea o sangre periférica fijados en acetona pura e incubados con el respectivo anticuerpo monoclonal. Posteriormente se añadió la inmunoglobulina anti ratón obtenida en conejo ( Linking ) y por último, el complejo APAAP. Los períodos de incubación fueron de 30 minutos y se realizaron lavados con solución amortiguadora entre cada uno de los pasos. La lectura de las láminas se realizó en microscopio óptico y se consideró positivo cuando el número de células marcadas era mayor o igual a 20 %. De los pacientes estudiados, el 93,3 % y el 90 %, respectivamente, expresaron antígenos pan mieloides CD13 y CD33; 16 de ellos expresaron el CD15 (53,3 %); 3 el CD19 (10 %) y 2 el CD41 (6,6 %). Se concluyó que el método APAAP es rápido y de bajo costo y puede ser aplicado con confiabilidad en la clasificación inmunológica de las leucemias mieloides agudas<br>The cellular immunophenotyping of 30 patients with the diagnosis of acute myeloid leukemia was conducted by the alkaline phosphatase anti-alkaline phosphatase immunocytochemical method (APAAP) introduced in our laboratory. The markers studied were: CD3, CD13, CD15, CD19, CD33 y CD41. Specimens of bone marrow or peripheral blood fixed in pure acetone and incubated with the respective monoclonal antibody were used for the study. Later on, the anti-mouse immunoglobulin obtained in rabbit (Linking) was added and, finally, the APAAP complex. The incubation periods were of 30 minutes and lavages with buffer solution were carried out between one step and the other. The reading of the slides was performed on the optical microscope and it was considered positive when the number of marked cells was higher than or equal to 20 %. Of the studied patients, 93.3 % and 90 %, respectively, expressed panmyeloid antigens CD13 and CD33; 16 of them expressed the CD15 (53.3 %); 3 the CD19 (10 %); and 2 the CD41 (6.6 %). It was concluded that the APAAP method is rapid and inexpensive and that it may be reliably applied in the immunological classification of the acute myeloid leukemia