Optimization and validation of PD-L1 immunohistochemistry staining protocols using the antibody clone 28-8 on different staining platforms.

Several immunohistochemistry (IHC) assays have been developed to assess tumor programmed death-ligand 1 (PD-L1) expression levels in patients who are candidates for programmed death-1 (PD-1)/PD-L1 inhibitor therapy. The PD-L1 IHC 28-8 pharmDx kit is FDA-approved as a complementary diagnostic and CE-marked as an in vitro diagnostic device for nivolumab therapy in melanoma and specific lung cancer subtypes (and for squamous cell carcinoma of the head and neck/urothelial carcinoma in Europe only). Kit availability is limited outside the United States, and its use requires the Dako Autostainer Link 48 platform, which is unavailable in many laboratories. Validated laboratory-developed tests based on 28-8 concentrated antibody outside the kit are needed. This study compared the results from PD-L1 expression level analysis across four immunohistochemistry platforms (Dako Autostainer Link 48, Dako Omnis, Leica Bond-III, and Ventana BenchMark ULTRA) with the 28-8 pharmDx kit in lung cancer (multiple histologies), melanoma, and head and neck cancer (multiple histologies). Samples were prepared per protocol for each platform and stained using PD-L1 IHC 28-8 pharmDx kit on Dako Autostainer Link 48, and per protocol for each platform. The control samples (tonsil and placenta tissue; cell lines with prespecified PD-L1 expression levels) were tested to evaluate the specificity and the sensitivity of test assays. An agreement level of 0.90 with the pharmDx kit was set for each platform. Inter- and intra-assay reliability were assessed. Evaluable samples were lung cancer = 29; melanoma = 31; head and neck cancer = 30. Mean agreement was calculated for PD-L1 expression levels of ≥1%, ≥5%, ≥10%, and ≥50%. Mean overall agreement for all indications was 0.87-0.99. Inter- and intra-assay of scoring/classification repeatability was 100%. Analysis of PD-L1 expression levels using laboratory-developed immunohistochemistry assays with 28-8 antibody may be permissible if the platform is validated using reference samples with defined expression levels.

Prescripción enfermera, función avanzada para el profesional de enfermería / Nurse prescribing, function of advanced nursing

La concepción de las funciones del personal de enfermería ha ido evolucionando a través del tiempo, así como su influencia en el desarrollo de la profesión. Motivados por esto se realizó una revisión bibliográfica con el objetivo de hacer una reflexión que lleve al debate sobre un tema que a nivel mundial viene tomando auge, la prescripción enfermera. Este ha tenido éxito en muchos países, dado que permite el desarrollo del ejercicio autónomo de la profesión de enfermería y la importancia que tiene en el reconocimiento de la labor de todos los integrantes del equipo de salud, promoviendo el respeto a la profesionalidad, dignidad, derechos y valores de todos sus miembros. Se concluye que las demandas de salud de la población, unidas al creciente desarrollo de la profesión, han generado un cambio en el rol del profesional de enfermería que lo Lleva a ampliar su perfil y realizar funciones de avanzada en su práctica, siendo la prescripción enfermera una realidad consolidada en diferentes países y una creciente disposición en el resto de los mismos.

The conception of the functions of nurses has evolved over time, as well as its influence in the development of the profession. Motivated by this, a literature review was conducted with the objective of making a reflection that leads the debate on an issue that is increasing world-wide, the nurse prescribing. It has been successful in many countries, as it allows the development of the autonomous exercise of the profession of nursing and the importance in recognizing the work of all health team members, promoting respect for the professionalism, dignity, rights and values of all its members. We conclude that that the health demands of the population, together with the increasing development of the profession; have generated a change in the role of the nurse who leads to expand their profile and perform functions of advanced practice, being the nurse prescription a consolidated reality in different countries and an increasing willingness in the rest of them.

Uso prudente de antibióticos y propuestas de mejora desde la farmacia comunitaria y hospitalaria / Prudent use of antibiotics and suggestions for improvement from community and hospital pharmacy

El uso prudente de antibióticos requiere un abordaje interdisciplinar en el que la farmacia, tanto hospitalaria como comunitaria, desempeña un papel importante. Las actividades que se realizan en la farmacia hospitalaria se pueden dividir en 3 fases: a) antes de la prescripción: mediante la selección de antimicrobianos, la elaboración de guías de profilaxis y tratamiento empírico, y la incorporación de las decisiones en programas informáticos que permitan una prescripción electrónica informada; b) durante la prescripción: evaluación de la prescripción, adecuación de la dosis y pauta a los datos del paciente y de la infección, preparación de las dosis listas para su uso, ajustes farmacocinéticos y monitorización de la duración de los tratamientos, y c) después del tratamiento: realizando auditorías clínicas y medidas de la utilización de antibióticos. Desde la farmacia comunitaria las actividades a realizar son fomentar la adherencia al tratamiento, el seguimiento farmacoterapéutico del paciente para prevenir y detectar problemas relacionados con la medicación, y evitar la dispensación sin prescripción médica. Como propuestas de mejora se considera principalmente la formación en el control del uso de antimicrobianos, la integración en equipos interdisciplinares y la no venta de medicamentos sin prescripción médica

Appropriate use of antibiotics requires an interdisciplinary approach in which hospital and community pharmacies play a key role. The activities carried out in hospital pharmacy can be divided into 3 stages: a) before prescription: through the selection of antimicrobial agents, the creation of guides on prophylaxis and empirical treatments, and incorporation of the decisions into computer programmes that provide detailed electronic prescriptions; b) during prescription: prescription assessment, dose adjustment, patient information and infection data, preparation of doses to be used, pharmacokinetic adjustments and monitoring of treatment duration, and c) after treatment: clinical audits and measurements of the use of antibiotics. In community pharmacy, activities include promoting patient compliance, pharmacotherapeutic follow-up of patients to prevent and detect drug-related problems and avoidance of over-the-counter drug dispensation. Suggestions for improvement include mainly training in monitoring the use of antimicrobials, integration in interdisciplinary teams and avoiding the sale of over-the-counter antibiotics

[Prudent use of antibiotics and suggestions for improvement from community and hospital pharmacy]. / Uso prudente de antibióticos y propuestas de mejora desde la farmacia comunitaria y hospitalaria.

Appropriate use of antibiotics requires an interdisciplinary approach in which hospital and community pharmacies play a key role. The activities carried out in hospital pharmacy can be divided into 3 stages: a) before prescription: through the selection of antimicrobial agents, the creation of guides on prophylaxis and empirical treatments, and incorporation of the decisions into computer programmes that provide detailed electronic prescriptions; b) during prescription: prescription assessment, dose adjustment, patient information and infection data, preparation of doses to be used, pharmacokinetic adjustments and monitoring of treatment duration, and c) after treatment: clinical audits and measurements of the use of antibiotics. In community pharmacy, activities include promoting patient compliance, pharmacotherapeutic follow-up of patients to prevent and detect drug-related problems and avoidance of over-the-counter drug dispensation. Suggestions for improvement include mainly training in monitoring the use of antimicrobials, integration in interdisciplinary teams and avoiding the sale of over-the-counter antibiotics.

El coheficiente de correlación de los rangos de Spearman: caracterización / The coheficiente of correlation of the ranges of Spearman: characterization

En el ámbito de las investigaciones clínico-epidemiológicas, los profesionales de la salud asiduamente se proyectan en sus investigaciones; se definen las relaciones entre las características de un fenómeno, el grado de esa relación o probar la confiabilidad de sus observaciones, planteándose como hipótesis si estas son o no la causa de una determinada entidad. En la práctica, generalmente, acontece que el investigador entre las disímiles pruebas estadísticas de las que dispone, no selecciona adecuadamente la que con mayor cientificidad le aportará una lectura fácil de dicha relaciones. Se realiza una revisión bibliográfica con el objetivo de caracterizar el método de correlación de rangos de Spearman, utilizado para valorar la asociación entre variables cuantitativas, aplicándose el método de análisis documental .Los resultados son declarados al resumir la historia del surgimiento de la teoría de la correlación y la regresión, explicación de conceptos asociados, su presentación gráfica, los rasgos esenciales del algoritmo de solución tradicional y con asesor estadístico, así como una compilación sobre escalas de interpretación de la prueba estadística. Se proyecta que el trabajo realizado sirva de bibliografía a consultar por investigadores y estudiantes de las Ciencias Médicas(AU)

In the environment of the investigations epidemic clinic, the professionals of the health assiduously are projected in their investigations, to define the relationships among the characteristics of a phenomenon, the grade of that relationship or to prove the dependability of their observations, thinking about as hypothesis if these they are or it doesn't cause it of a certain entity. In the practice it generally happens that the investigator among the dissimilar statistical tests of those that prepares doesn't select appropriately the one that will contribute him a reading with more exactitude, easy of these relations. Se he carries out a bibliographical revision with the objective of characterizing the method of correlation of ranges of Spearman, used to value the association among quantitative variables, being applied the method of documental analysis. The results are declared when summarizing the history of the emergence of the theory of the correlation and the regression, explanation of associate concepts, his graphic presentation, the essential features of the algorithm of traditional solution and with advisory statistical as well as a compilation on scales of interpretation of the statistical test. He/she is projected that the carried out work serves from bibliography to consult for investigators and students of the Medical sciences(AU)

El coeficiente ee correlacion de los rangos de spearman caracterizacoon / Characteization of the spearman correlation ranks coefficient

En el ámbito de las investigaciones clínico-epidemiológicas, los profesionales de la salud asiduamente se proyectan en sus investigaciones; se definen las relaciones entre las características de un fenómeno, el grado de esa relación o probar la confiabilidad de sus observaciones, planteándose como hipótesis si estas son o no la causa de una determinada entidad. En la práctica, generalmente, acontece que el investigador entre las disímiles pruebas estadísticas de las que dispone, no selecciona adecuadamente la que con mayor cientificidad le aportará una lectura fácil de dicha relaciones. Se realiza una revisión bibliográfica con el objetivo de caracterizar el método de correlación de rangos de Spearman, utilizado para valorar la asociación entre variables cuantitativas, aplicándose el método de análisis documental .Los resultados son declarados al resumir la historia del surgimiento de la teoría de la correlación y la regresión, explicación de conceptos asociados, su presentación gráfica, los rasgos esenciales del algoritmo de solución tradicional y con asesor estadístico, así como una compilación sobre escalas de interpretación de la prueba estadística. Se proyecta que el trabajo realizado sirva de bibliografía a consultar por investigadores y estudiantes de las Ciencias Médicas.

In the environment of the investigations epidemic clinic, the professionals of the health assiduously are projected in their investigations, to define the relationships among the characteristics of a phenomenon, the grade of that relationship or to prove the dependability of their observations, thinking about as hypothesis if these they are or it doesn't cause it of a certain entity. In the practice it generally happens that the investigator among the dissimilar statistical tests of those that prepares doesn't select appropriately the one that will contribute him a reading with more exactitude, easy of these relations. Se he carries out a bibliographical revision with the objective of characterizing the method of correlation of ranges of Spearman, used to value the association among quantitative variables, being applied the method of documental analysis. The results are declared when summarizing the history of the emergence of the theory of the correlation and the regression, explanation of associate concepts, his graphic presentation, the essential features of the algorithm of traditional solution and with advisory statistical as well as a compilation on scales of interpretation of the statistical test. He/she is projected that the carried out work serves from bibliography to consult for investigators and students of the Medical sciences.

An integral approach towards a practical application for a plant-made monoclonal antibody in vaccine purification.

The use of transgenic plants for the production of pharmaceutical compounds has received increasing attention in the last few years. However, many technological and regulatory issues regarding the practical exploitation of this alternative system of production remain to be solved; a situation that explains the lack of commercial products derived from such a system. This paper reports the expression in transgenic plants and cells of a single-chain antibody variable-region fragment (scFv) and a mouse monoclonal antibody to the hepatitis B virus surface antigen (HBsAg). The large-scale purification of the scFv from plants and its use for immunopurification of HBsAg are also described, together with elements concerning regulatory issues and technologies for compliance with good manufacturing and agricultural practices.

Oral N-acetylcysteine attenuates elastase-induced pulmonary emphysema in rats.

STUDY OBJECTIVE: To study the effect of the antioxidant N-acetylcysteine (NAC) in the development of elastase-induced emphysema in rats. MATERIALS AND METHODS: Wistar rats (n = 72) were orotracheally instilled with 75 IU elastase or saline solution. Eighteen rats from each group received the antioxidant NAC from 2 days before induction of the lesion until they were killed 2, 8, and 28 days after instillation. The effects of treatment were assessed by measuring collagen content for the left lung, a histopathology evaluation (ie, mean alveolar internal surface area (AIA) and mean linear intercept measurement), and lung function. RESULTS: Twenty-eight days after elastase instillation, rats treated with NAC showed significant attenuation of the lesion in comparison with rats treated only with elastase, including the following: normalization of mean (+/- SEM) collagen content (1.23 +/- 0.09 vs 1.51 +/- 0.10 mg per left lung, respectively; p < 0.05); partial inhibition of mean AIA (14,860 +/- 1,135 vs 19,622 +/- 1,294 micro m(2), respectively; p < 0.05) and mean linear intercept (108.8 +/- 3.7 vs 123.0 +/- 4.2 micro m, respectively; p < 0.05); and increases and improvement in expiratory flows (27.8 +/- 1.2 vs 23.4 +/- 1.3 mL/s, respectively; p < 0.05). NAC was not able to avoid the compliance increase in the elastase-plus-NAC group. CONCLUSION: Consistent with the results of anatomic, pathologic, and functional studies, NAC is able to attenuate the lesions induced by elastase in rats, which is in accordance with previous data supporting the idea that oxidant injury could contribute to the development of elastase-induced emphysema.

Gene therapy with galectin-3 inhibits bronchial obstruction and inflammation in antigen-challenged rats through interleukin-5 gene downregulation.

The pathophysiology of asthma involves an intricate network of molecular and cellular interactions. Elevated Th2 cytokines (interleukin [IL]-5 and IL-4) associated with eosinophilic inflammation characterize allergic diseases and provide potential targets for immunomodulation. Recent evidence has demonstrated that galectin-3 induces selective downregulation of IL-5 gene expression in several cell types (eosinophils, T cell lines, and antigen specific T cells). Accordingly, we sought to elucidate whether in vivo intratracheal instillation of plasmid DNA encoding galectin-3 would inhibit an experimental asthmatic reaction in a rat model with increased eosinophils and T cells in bronchoalveolar fluid and impaired pulmonary function. We found that instillation of galectin-3 gene in these rats led to normalization of the eosinophil and T cell count in bronchoalveolar lavage fluid and that there was a strong concomitant inhibition of IL-5 mRNA in the lungs. As a consequence, galectin-3-treated rats showed recovery of pulmonary functional parameters, such as pulmonary pressure and expiratory flows. These data emphasize the potential utility of galectin-3 as a novel therapeutic approach for treatment of allergic asthma.

Estrategia para el establecimiento de las especificaciones de calidad en el centro de ingeniería genética y biotecnología de la Habana, Cuba / Strategy for setting the quality specifications at the center for genetic engineering and biotechnology in Havana, Cuba

El establecimiento de las especificaciones de calidad es un paso importante en el desarrollo de un nuevo producto biofarmacéutico y constituyen un compromiso legal con las autoridades regulatorias en le campo de los medicamentos. En el trabajo se presenta la estrategia seguida en el centro de ingeniería genética y biotecnología de la Habana, Cuba para el establecimento de las especificaciones de calidad...(AU)

Traumatismo en el cuello como causa de oclusión aguda de la arteria central de la retina / Neck traumatism as cause of acute occlusion for central artery of the retina

Se ha descrito la oclusión de la arteria carótida interna y de las arterias vertebrales, entre otras causas, por traumatismos o manipulaciones del cuello; más raramente, se han comunicado casos en que los vasos ocluidos son parte de los sistemas vasculares a que ellas dan origen, como la arteria cerebral media, el tronco basilar y la cerebelosa porteroinferior. Se presenta el caso de un paciente que sufrió una oclusión aguda de la arteria central de la retina, secundaria a un traumatismo en la región lateral del cuello, con conservación de la visión central por la existencia de una arteria ciliorretiniana permeable, y su evolución a través de dos años. Se discuten aspectos fisiopatológicos y la importancia práctica que tiene para el oftalmólogo considerar este factor causal, así como mantener una estrecha relación con el neurólogo por las implicaciones que pueden tener estos traumatismos sobre el sistema nervioso central(AU)