Correction: The anti-metastatic activity of collagenase-2 in breast cancer cells is mediated by a signaling pathway involving decorin and miR-21.

The original microRNA hybridization data for this article, which has been available for the scientific community upon request, has now been deposited in the GEO repository under accession number GSE124432.

Quality assessment of buffy-coat-derived leucodepleted platelet concentrates in PAS-plasma, prepared by the OrbiSac or TACSI automated system.

BACKGROUND AND OBJECTIVES: Buffy-coat (BC)-derived platelet concentrates (PCs) are the predominant product for platelet transfusion in many countries. Two automated systems, OrbiSac and TACSI, have been introduced in blood centres to prepare these PCs, as an alternative to the manual method. We compared the in vitro quality of PCs prepared by both methods during standard storage. STUDY DESIGN AND METHODS: Twenty primary BC pools were split into two parts, which were processed with OrbiSac and TACSI system to obtain OrbiSac PCs (O-PCs) and TACSI PCs (T-PCs), respectively. On days 1, 5 and 7 of standard storage, samples were taken and the following analysed: cell count, metabolic variables, platelet function and content of activation and proinflammatory substances. RESULTS: Both the OrbiSac and TACSI systems produced PCs that meet the standards for platelet products in terms of platelet and leucocyte content. In vitro evaluation pointed to the similar preservation of platelet metabolism (pH, glucose, bicarbonate and lactate) in O-PCs and T-PCs. Moreover, there were no significant differences between O-PCs and T-PCs as regards the hypotonic shock response or in the platelet aggregation profile. The OrbiSac system caused greater platelet activation, which resulted in higher concentrations of sCD62P, RANTES and sCD40L on the day the PCs were prepared. CONCLUSION: The systems OrbiSac and TACSI can be used to produce buffy-coat-derived PCs whose cell content, platelet function and metabolism are similar during standard storage. However, the preparation with the OrbiSac system induces a transient increase in platelet activation and release of proinflammatory substances.

The anti-metastatic activity of collagenase-2 in breast cancer cells is mediated by a signaling pathway involving decorin and miR-21.

Matrix metalloproteinases (MMPs) have been traditionally implicated in cancer progression because of their ability to degrade the extracellular matrix. However, some members of the MMP family have recently been identified as proteases with antitumor properties. Thus, it has been described that collagenase-2 (MMP-8) has a protective role in tumor and metastasis progression, but the molecular mechanisms underlying these effects are unknown. We show herein that Mmp8 expression causes a decrease in miR-21 levels that in turn leads to a reduction in tumor growth and lung metastasis formation by MDA-MB-231 (4175) breast cancer cells. By using both in vitro and in vivo models, we demonstrate that the mechanism responsible for these MMP-8 beneficial effects involves cleavage of decorin by MMP-8 and a subsequent reduction of transforming growth factor ß (TGF-ß) signaling that controls miR-21 levels. In addition, miR-21 downregulation induced by MMP-8 increases the levels of tumor suppressors such as programmed cell death 4, which may also contribute to the decrease in tumor formation and metastasis of breast cancer cells overexpressing this metalloproteinase. These findings reveal a new signaling pathway for cancer regulation controlled by MMP-8, and contribute to clarify the molecular mechanisms by which tumor-defying proteases may exert their protective function in cancer and metastasis.

[The enigma of quaternary prevention in Primary Care. When and when not to do it (presentation of two cases)]. / El enigma de la prevención cuaternaria en atención primaria. Cuándo hacer y cuándo no hacer (a propósito de 2 casos).

Quaternary prevention has been commonly defined with the "primum non nocere" of classical texts by many authors. The daily life of our primary care consultations are full of patients in which we wondered if we try to obtain the benefit of our intervention will exceed the damage we cause him to intervene. Patients with multiple comorbidities, polypharmacy and complex are common in our consultations and it is becoming more difficult to move the balance of our actions, diagnostic or therapeutic benefit to the side. Through 2 cases often move to the reflection of this problem. Quaternary prevention must also be present in our daily activities.

El enigma de la prevención cuaternaria en atención primaria. Cuándo hacer y cuándo no hacer (a propósito de 2 casos) / The enigma of quaternary prevention in Primary Care. When and when not to do it (presentation of two cases)

La prevención cuaternaria ha sido definida comúnmente con el «primun non nocere» de los textos clásicos por muchos autores. El día a día de nuestras consultas en Atención Primaria están llenas de pacientes en las que nos preguntamos si el beneficio que pretendemos obtener con nuestra intervención superará el perjuicio que le ocasionamos al intervenir. Los pacientes pluripatológicos, polimedicados y complejos son frecuentes en nuestras consultas y cada vez se hace más complicado mover la balanza de nuestras actuaciones, diagnósticas o terapéuticas, hacia el lado del beneficio. A través de 2 casos clínicos frecuentes movemos a la reflexión de este problema. La prevención cuaternaria también debe estar presente en nuestra actividad diaria(AU)

Quaternary prevention has been commonly defined with the “primum non nocere” of classical texts by many authors. The daily life of our primary care consultations are full of patients in which we wondered if we try to obtain the benefit of our intervention will exceed the damage we cause him to intervene. Patients with multiple comorbidities, polypharmacy and complex are common in our consultations and it is becoming more difficult to move the balance of our actions, diagnostic or therapeutic benefit to the side. Through 2 cases often move to the reflection of this problem. Quaternary prevention must also be present in our daily activities(AU)

The KRAS mutation detection within the initial management of patients with metastatic colorectal cancer: a status report in France in 2011.

BACKGROUND: The detection of KRAS mutations is mandatory to initiate an anti-epidermal growth factor receptor (EGFR) antibody in the treatment of metastatic colorectal carcinoma (mCRC). PATIENTS AND METHODS: This observational retrospective study was performed in 160 French centres during a 2-week period in 2011. Its main objective was to evaluate the rate of KRAS testing in patients with mCRC having initiated their first-line therapy. Secondary objectives included time of process, techniques used and reasons for non-prescription. RESULTS: Five hundred and thirty eight mCRC patients (67.1 ± 11.3 years, synchronous metastases: 69.9%) were enrolled in the study. KRAS testing was prescribed in 81.1% of patients, in a median of 15 days after the diagnosis of metastases, and of 15 days prior to the initiation of the first-line metastatic chemotherapy. KRAS status was available for 87% of patients, after 23.6 ± 28.2 days, but after the choice of the first-line therapy in 56.6% of patients. Heterogeneity of reception time was noteworthy within regions (8.3 ± 7 days to 38.8 ± 101 days). KRAS testing was not prescribed mainly due to the planned non-prescription of an anti-EGFR antibody. CONCLUSION: This study confirmed that KRAS testing is definitely part of the management of most of mCRC patients, despite discrepancies observed in the rate of prescription and the time of results.

[Creation of a unit for education in the self-management of oat]. / Creación de una unidad de educación en el autocontrol del TAO.

Oral anticoagulant therapy (OAT) with Vitamin K antagonists requires frequent analytical controls that create a certain degree of dependency and a loss of autonomy in the patient. These drugs have an undesirable variability due to food and drug interactions, febrile processes, etc. which can modify the patient's INR and predispose them to a thromboembolic or hemorrhagic event. OAT self-control is supported by more than 15 years of experience in countries such as Germany and the Netherlands, and by comparative studies that reflect a reduction of thromboembolism and other adverse effects. The reason of this is because these patients are in the correct therapeutic range for longer periods of time due to more frequent controls (once a week against every 4-5 weeks of traditional control) and also to a better understanding of their treatment. In Aragon, OAT is a free health service and in our hospital, OAT has been an institutional aim since 2070. After a training course, the patient is capable to make their own INR determinations at home, to evaluate their results and adjust their own dose. Additionally the patient should acquire the appropriate knowledge to detect any adverse symptom and to know how to react to any problem in their treatment. This article summarizes our experience regarding the implementation of the programme and creation of the specific unit: the organization and training of the professionals involved, establishment of the patient selection criteria, and design of the patients' training course, follow-up strategy and equipment. In addition, the results of the study conducted in our Unit, showing a high degree of patient satisfaction, are included. At this moment 20% of our patients are included in the self-control strategy.

Creación de una unidad de educación en el autocontrol del TAO / Creation of a unit for education in the self-management of OAT

El tratamiento anticoagulante oral (TAO) con antagonistas de la vitamina K requiere frecuentes controles analíticos que crean en el paciente un cierto grado de dependencia y pérdida de autonomía. Estos fármacos tienen un indeseable efecto variable debido a interacciones medicamentosas, alimentarias, comorbilidad, etc. que puede provocar una modificación de la INR (International Normalized Ratio) del rango terapéutico correcto y la posibilidad de sufrir algún evento tromboembólico o hemorrágico. El programa de autocontrol del TAO está avalado por una experiencia superior a 15 años en países como Alemania y Holanda, y por numerosos estudios en los que queda reflejada una reducción de los efectos adversos, principalmente de carácter tromboembólico. Esto es debido a que los pacientes se encuentran más tiempo en el rango terapéutico correcto, al ser más frecuentes los controles analíticos y ajustes de dosis (una vez a la semana frente a las 4-5 semanas del control tradicional) y a un mejor conocimiento de su tratamiento. En la CCAA de Aragón esta prestación sanitaria gratuita y en nuestro hospital es un objetivo institucional desde el año 2010. El programa consiste en capacitar al paciente para realizarse la determinación de la INR en su autoanalizador, interpretar el resultado y ajustar su propia dosis acomodándola a los cambios sufridos. Así mismo, debe adquirir los conocimientos adecuados para advertir cualquier síntoma adverso y saber reaccionar ante cualquier problema en su tratamiento. En este artículo relatamos nuestra experiencia en la creación de la unidad y la implantación del programa: estructuración y formación de los profesionales implicados, elección de los criterios en la selección de los pacientes, material necesario, diseño del curso de aprendizaje de los pacientes, estrategia de la evolución y seguimiento. Además se incluyen los resultados de un estudio realizado en nuestra unidad, donde se muestra el alto grado de satisfacción de los pacientes adscritos. Se ha logrado implantar el programa con una gran aceptación. Actualmente se halla incluido el 20% del total de asistidos(AU)

Oral anticoagulant therapy (OAT) with Vitamin K antagonists requires frequent analytical controls that create a certain degree of dependency and a loss of autonomy in the patient. These drugs have an undesirable variability due to food and drug interactions, febrile processes, etc. which can modify the patient's INR and predispose them to a thromboembolic or hemorrhagic event. OAT self-control is supported by more than 15 years of experience in countries such as Germany and the Netherlands, and by comparative studies that reflect a reduction of thromboembolism and other adverse effects. The reason of this is because these patients are in the correct therapeutic range for longer periods of time due to more frequent controls (once a week against every 4-5 weeks of traditional control) and also to a better understanding of their treatment. In Aragon, OAT is a free health service and in our hospital, OAT has been an institutional aim since 2010. After a training course, the patient is capable to make their own INR determinations at home, to evaluate their results and adjust their own dose. Additionally, the patient should acquire the appropriate knowledge to detect any adverse symptom and to know how to react to any problem in their treatment. This article summarizes our experience regarding the implementation of the programme and creation of the specific Unit: the organization and training of the professionals involved, establishment of the patient selection criteria, and design of the patients' training course, follow-up strategy and equipment. In addition, the results of the study conducted in our Unit, showing a high degree of patient satisfaction, are included. At this moment 20% of our patients are included in the self-control strategy (AU)

[Role of pathologic anatomy in the diagnosis, prognostic evaluation, and surveillance of bladder tumors]. / Place de l'anatomie pathologique dans le diagnostic, l'évaluation pronostique et la surveillance des tumeurs de vessie.

The usual histological techniques are necessary and sufficient for the routine diagnosis of bladder tumours. Many laboratory tools are designed to determine prognostic factors but require such technical conditions that they cannot be used routinely. The determination of DNA ploidy by flow cytometry of voided urine, fresh, formalin-fixed or paraffin-embedded tumour fragments is a simple, standardised and reproducible technique and the method of choice of pathologists as it allows morphological control of the element analysed. Based on a series of 720 bladder tumours collected by 3 different centres, the authors demonstrate how to use, correlate and integrate into routine practice the data of image analysis flow cytometry in relation to conventional cytology and histology. 5% of grade 1 tumours, 27% of grade 2 tumours, and 92% of grade 3 tumours were DNA aneuploid. 17% of non-invasive tumours (PTa) and 79% of invasive tumours (PT1 and more) were DNA aneuploid. These proportions are in line with the results of various series in the literature. DNA ploidy is therefore an objective and measurable element completing histological grading. The determination of DNA ploidy also helps the cytologist in difficult cases of urine cytology.

Malignant adenomyoepithelioma of the breast. An immunohistochemical, cytophotometric, and ultrastructural study of a case with lung metastases.

Adenomyoepithelioma of the breast is a rare tumor that, on the basis of histologic, immunohistochemical, and ultrastructural features, has a bicellular pattern of epithelial and myoepithelial cells regularly distributed in tubular structures. Until now, this tumor was thought to be a benign or low-grade malignant lesion because of possible local recurrences (7 recurrent cases of 60 in the literature). Only one of these cases had nodal involvement, thereby suggesting the possible malignancy of this lesion. This paper reports the first documented case of malignant adenomyoepithelioma with lung metastases presenting the same biphasic pattern as the primary tumor.

Granulomatous hepatitis in Q fever.

Liver lesions in 17 patients with serologically diagnosed Q fever are described. A distinctive granulomatous pattern, with granuloma formation plus a fibrinoid ring, was observed in 14 cases. In two cases the fibrinoid material consisted of fibrillar eosinophilic structures without an annular arrangement, interspersed among epithelioid cells. In only one case was a nonspecific granuloma (devoid of fibrinoid material) noted. We conclude that the association of a granuloma with fibrinoid material is highly indicative of Q fever, but serial sections are often necessary to demonstrate this pattern.

Leukoerythroblastosis and cancer frequency, prognosis, and physiopathologic significance.

This investigation was carried out on 100 bone marrow biopsies with metastases and 56 autopsies on patients with evidence of cancer. Leukoerythroblastosis was found in 44% of the patients with bone marrow mestastases and was more frequent in prostatic and gastric carcinoma. Moreover, the postmortem study of patients who died with cancer showed that leukoerythroblastosis was always the sign of bone marrow metastasis. A significant correlation was found between these blood changes and bone marrow fibrosis around the metastasis. Furthermore, leukoerythroblastosis seems caused by hepatosplenic extra medullary hematopoiesis.