Características clinicoepidemiológicas de pacientes tratados con hemoderivados en un hospital de Santiago de Cuba / Clinical and epidemiological characteristics of patients treated with blood-derivatives in a hospital from Santiago de Cuba

Introducción: El uso de hemoderivados es una práctica habitual en los hospitales y muy efectiva en determinadas situaciones clínicas. Objetivo: Caracterizar clínica y epidemiológicamente a pacientes tratados con hemoderivados en el Hospital Provincial Docente Dr. Joaquín Castillo Duany de Santiago de Cuba. Métodos: Se realizó un estudio descriptivo y transversal de 394 pacientes que estuvieron ingresados en el Hospital Provincial Docente Dr. Joaquín Castillo Duany de Santiago de Cuba, desde enero hasta junio de 2018, que recibieron transfusión de hemoderivados. Los datos se obtuvieron de las historias clínicas y para el procesamiento se empleó el paquete estadístico SPSS, versión 23. Resultados: En la serie predominaron el sexo masculino (50,7 %), la transfusión de eritrocitos y los pacientes transfundidos con cifras de hemoglobina entre 70 y 89 g/L (47,7 %). En el Servicio de Cirugía General fue donde más se transfundió (43,2 %) y, en general, se detectaron múltiples deficiencias en las órdenes de transfusiones. Conclusiones: No existieron diferencias significativas en cuanto al sexo y los pacientes intervenidos quirúrgicamente fueron los que más recibieron este tratamiento. Hubo incumplimiento del protocolo hospitalario previsto y la omisión de datos en las órdenes de transfusiones afectó la calidad de la hemovigilancia.

Introduction: The use of blood-derivatives is an usual practice in hospitals and very effective in certain clinical situations. Objective: To characterize clinical and epidemiologically patients treated with blood-derivatives at Dr. Joaquín Castillo Duany Teaching Provincial Hospital in Santiago de Cuba. Methods: A descriptive and cross-sectional study of 394 patients that were admitted to Dr. Joaquín Castillo Duany Teaching Provincial Hospital and received blood-derivatives transfusion was carried out in Santiago de Cuba, from January to June, 2018. The data were obtained from the medical records and for its processing the SPSS statistical package, version 23 was used. Results: In the series there was a prevalence of the male sex (50.7 %), transfusion of erythrocytes and transfused patients with hemoglobin figures between 70 and 89 g/L (47.7 %). There were more transfusions in the General Surgery Service (43.2 %) and, in general, multiple deficiencies were detected in the orders of transfusions. Conclusions: As for sex there were no significant differences and patients surgically intervened were those that received this treatment more times. There was no fulfilment of the foreseen hospital protocol and the omission of data in the orders of transfusions affected the blood safety quality.

L-PRF Membrane (Fibrin Rich in Platelets and Leukocytes) and Its Derivatives (A-PRF, i-PRF) are Helpful as a Basis of Stem Cells in Regenerative Injury Treatment: Trial Work on the Horse

Developing a multidisciplinary field of tissue engineering aims to recover, improve or supplant typically damaged or missing tissues for a collection of conditions brought about by trauma, malady and old age. To guarantee that tissue engineering techniques are generally relevant in the clinical setting, it is important to adjust them so that they are promptly accessible and moderately simple to use in the everyday clinical schedule. Consequently, the steps between preparation and application must be limited and improved to make them practical in application. The general objective of creating platelet concentrates of natural origin can be delivered near the patient to quicken the implantation procedure, being monetarily practical for the patient and the health framework. Fibrin rich in platelets and leukocytes (PRF) and its derivatives (L-PRF, A-PRF, i-PRF) has been utilized in a wide collection of medical fields for delicate tissue restoration. Practically all platelets (> 97%) are missing within test-tubes in groups tested after PRF membrane extraction. Growth Factors liberated by platelets contained in derivatives of L-PRF induce and control the proliferation and migration of other cell types, associated with tissue repair, similar to smooth cell muscles (SMCs) and mesenchymal stem cells (MSCs). Conclusively, the outcomes of this work feature the positive effects of PRF on wound healing after regenerative treatment for the administration of different delicate tissue defects found in wound care.

Venous Blood Derivatives as FBS-Substitutes for Mesenchymal Stem Cells: A Systematic Scoping Review

Abstract Although the biological properties of mesenchymal stem cells (MSC) are well-characterized in vitro, MSC clinical application is still far away to be achieved, mainly due to the need of xenogeneic substances for cell expansion, such as fetal bovine serum (FBS). FBS presents risks regarding pathogens transmissions and internalization of animal's proteins, which can unleash antigenic responses in patients after MSC implantation. A wide range of venous blood derivatives (VBD) has been reported as FBS substitutes showing promising results. Thus, the aim of this study was to conduct a systematic scoping review to analyze whether VBD are effective FBS substitutes for MSC ex vivo expansion. The search was performed in SciVerse ScopusTM, PubMed, Web of ScienceTM, BIREME, Cochrane library up to January 2016. The keywords were selected using MeSH and entry terms. Two independent reviewers scrutinized the records obtained considering specific inclusion criteria. The included studies were evaluated in accordance with a modified Arksey and O' Malley's framework. From 184 found studies, 90 were included. Bone marrow mesenchymal stem cells (BMMSC) were presented in most of these studies. Overall, VBD allowed for either, maintenance of MCS's fibroblast-like morphology, high proliferation, high colony-formation ability and maintenance of multipotency. Besides. MSC expanded in VBD supplements presented higher mitogen activity than FBS. VBD seems to be excellent xeno-free serum for ex vivo expansion of mesenchymal stem cells. However, an accentuated heterogeneity was observed between the carried out protocols for VBD isolation did not allowing for direct comparisons between the included studies.

Resumo Embora as propriedades biológicas das células-tronco mesenquimais (MSC) sejam bem caracterizadas in vitro, a aplicação clínica das MSC ainda está longe de ser alcançada, principalmente devido à necessidade de substâncias xenogênicas para expansão celular, como o soro fetal bovino (FBS). O FBS apresenta riscos quanto às transmissões de patógenos e à internalização de proteínas animais, o que pode desencadear respostas antigênicas em pacientes após a implantação das MSC. Uma vasta gama de derivados do sangue venoso (VBD) têm sido relatada como substitutos do FBS mostrando resultados promissores. Assim, o objetivo deste estudo foi conduzir uma revisão de escopo sistemática para analisar se VBD poderiam ser substitutos do FBS eficazes para expansão das MSC em condições ex vivo. A pesquisa foi realizada no SciVerse Scopus, PubMed, Web of Science, BIREME e biblioteca Cochrane até janeiro de 2016. As palavras-chave foram selecionadas usando MeSH e entre termos. Dois revisores independentes examinaram os registros obtidos considerando critérios de inclusão específicos. Os estudos incluídos foram avaliados de acordo com uma estrutura modificada de Arksey e O 'Malley. Dos 184 estudos encontrados, 90 foram incluídos. As células-tronco da medula óssea (BMMSC) foram utilizadas na maior parte destes estudos. Em geral, o VBD permitiu tanto a manutenção da morfologia semelhante a fibroblastos das MCS, alta proliferação, alta capacidade de formação de colônias e manutenção de multipotêncialidade. Além disso, as MSC expandidas em suplementos derivados do sangue venoso apresentaram uma maior atividade mitogênica do que as expandidas em FBS. Os VBD parecem ser excelentes soro livres de agentes xenogênicos para expansão ex vivo de MSC. Entretanto, observou-se uma heterogeneidade acentuada entre os protocolos realizados para o isolamento VBD, não permitindo assim comparações diretas entre os estudos incluídos.

La hemotransfusión en los Testigos de Jehová como un problema de las Ciencias Médicas / Blood transfusion in Jehovah's Witnesses as a problem in Medical Sciences

Introducción: los Testigos de Jehová basan sus creencias sobre una interpretación literal de la Biblia y no aceptan la transfusión de sangre o sus derivados. Pero no siempre se consigue por medio de las opciones médicas a la transfusión, evitar la muerte del individuo en determinadas circunstancias: ello plantea un conflicto bioético. Objetivo: analizar algunos aspectos bioéticos y legales, que puedan ayudar al anestesiólogo cubano a una mejor comprensión de este conflicto y a su solución ante la perspectiva de hemotransfundir a un paciente Testigos de Jehová. Desarrollo: los peligros de la transfusión sanguínea hacen considerar siempre medidas alternativas. Los pacientes Testigos de Jehová plantean un desafío a las Ciencias Médicas que ha estimulado el avance del conocimiento y la tecnología sobre dichas alternativas en beneficio de todos los pacientes; pero renegar tácitamente de la transfusión puede eventualmente introducir la posibilidad de que un paciente muera aunque existan opciones para salvarle. La práctica compele establecer antes de cualquier procedimiento quirúrgico protocolos específicos y líneas de comunicación entre paciente, anestesiólogo, cirujano, administración del hospital y el consejo legal. Conclusiones: el progreso de las investigaciones en las Ciencias Médicas está llamado a sustituir la reposición de sangre o sus derivados por las implicaciones biológicas que estos tratamientos médicos conllevan y no por cortapisas de un fanatismo religioso, que intenta arrebatar argumentos científicos para justificar sus creencias. En nuestro medio este conflicto bioético tiene solución dentro de un marco ético y legal en el que prevalece el bien supremo: la vida humana.

Background: Jehovah's Witnesses base their beliefs on a literal interpretation of the Bible and do not accept blood transfusions or its derivatives. But, by means of medical options to transfusion, the prevention of the death of the individual in certain circumstances is not always achieved: this causes a bioethical conflict. Objective: to analyze some bioethical and legal aspects that can help the Cuban anesthesiologist to a better understanding of this conflict and its solution in the perspective of giving a blood transfusion to a Jehovah's Witness patient. Development: the dangers of blood transfusion make us consider alternative measures. Jehovah's Witness patients pose a challenge to the Medical Sciences that has stimulated the advance of knowledge and technology on such alternatives for the benefit of all patients, but tacitly deny blood transfusion may eventually introduce the possibility that a patient dies even when there are options to save him. Practice obliges to establish specific protocols and lines of communication between patient, anesthesiologist, surgeon, hospital management, and legal advice before any surgical procedure. Conclusions: the progress of research in the Medical Sciences is oriented to substitute blood replacement or its derivatives because of the biological implications that these treatments bear rather than the obstacles of a religious fanaticism that tries to snatch scientific arguments to justify their beliefs. In our means, this bioethical conflict is solved within an ethical and legal framework in which a supreme good prevails: human life.

Mejora de la calidad en el consentimiento informado / Enhancement of informed consent quality / Melhora da qualidade no consentimento informado

Objetivo: Aplicar un círculo de mejora al consentimiento informado para la transfusión de hemoderivados. Pacientes y Método: Durante 10 meses se incluyeron 577 pacientes intervenidos en el Hospital General Reina Sofía de Murcia. Seleccionamos 6 criterios relacionados con el cumplimiento de la normativa sobre transfusiones. Tras el análisis de calidad, se aplicaron medidas correctoras y se reevaluaron los criterios. Los datos se compararon con los estándares en ambos periodos y entre periodos. En la primera evaluación se obtuvo un pobre cumplimiento de los criterios. Basándonos en el análisis de factores asociados al incumplimiento y la priorización resultante del diagrama de Pareto, el plan de intervención se dividió en actividad docente y modificaciones organizativas. Resultados: Todos los criterios estaban por debajo del estándar (p<0,001). En la segunda evaluación el cumplimiento de todos los criterios mejoró significativamente respecto de la primera; aun así los resultados continúan, también significativamente, por debajo de los estándares establecidos. Conclusiones: El cumplimiento de los 6 criterios era mínimo al inicio del estudio; las medidas correctoras fueron adecuadas, puesto que mejoraron todos ellos en la segunda evaluación, pero es necesario insistir en estas medidas ya que continuamos por debajo del estándar establecido.

Aim: To apply an enhancement circle for informed consent for transfusion of blood derivatives. Patients and Method: During 10 months 577 intervened patients were included in General Hospital Reina Sofia of Murcia, Spain. Six criteria were selected related to compliance with transfusion norms. After quality analysis, corrected measures were taken and the criteria were re evaluated. Data were compared with standards in both periods and between periods. In the first evaluation a poor compliance to criteria was observed. Based on the analysis of factors associated to lack of compliance and the resulting priorization from Pareto’s diagram, the intervention plan was divided in teaching activity and management modifications. Results: all criteria were under the standard (p<0.001). In the second evaluation, compliance for all criteria was significantly enhance with respect to the first; but nevertheless, results continue, also significantly, under established standards. Conclusions: Compliance to the six criteria was minimum at the beginning of the study; corrected measures were adequate, since they enhance all of them in the second evaluation, but it is necessary to insist in these measures since we continue under the established standard.

Objetivo: Aplicar um círculo de melhora ao consentimento informado para a transfusão de hemoderivados. Pacientes e Método: Durante 10 meses foram incluídos 577 pacientes internados no Hospital General Reina Sofía de Murcia. Selecionamos 6 critérios relacionados com o cumprimento da norma sobre transfusões. Após a análise de qualidade, foram aplicadas medidas corretoras e se reavaliaram os critérios. Os dados foram comparados com os padrões em ambos periodos e entre periodos. Na primeira avaliação se obteve um pobre cumprimento dos critérios. Baseando-nos na análise de fatores associados ao incumprimento e a priorização resultante do diagrama de Pareto, o plano de intervenção se dividiu em atividade docente e modificações organizativas. Resultados: Todos os critérios estavam abaixo do padrão (p<0,001). Na segunda avaliação o cumprimento de todos os critérios melhorou significativamente com respeito à primeira; ainda assim os resultados continuam, também significativamente, abaixo dos padrões estabelecidos. Conclusões: O cumprimento dos 6 critérios era mínimo ao início do estudo; as medidas corretoras foram adequadas, posto que melhoraram todos eles na segunda avaliação, porém é necessário insistir nestas medidas já que continuamos abaixo do padrão estabelecido.

A new methodology for polyvalent intravenous immunoglobulin solution production with a two-stage process of viral inactivation

Highly purified intravenous immunoglobulin G concentrate (IV IgG) was produced with the use of polyethylene glycol associated to a single-stage precipitation by ethanol, instead of the classic Cohn-Oncley process, which employs cold alcohol as the precipitating agent, in a three-stage process. Precipitation of crude fraction containing more than 95% of immunoglobulin G was performed by liquid chromatography with a cation exchanger, CM-Sepharose, as a stationary phase. During the process, the product was subjected to two-stage viral inactivation. The first stage was performed by the action of sodium caprylate, 30 mM at pH 5.1+/- 0.1, and the second stage was performed by the action of a solvent-detergent mixture. The finished product was formulated at 5% with 10% sucralose as the stabilizing agent. The process yields 3.3g of IgG/liter of plasma. The finished product analysis showed an anti-complementary activity lower than 1CH50. Polymer and aggregate percent levels were lower than 3% in the five batches studied. The analysis of neutralizing capacity showed the presence of antibacterial and antiviral antibodies in at least three times higher concentrations than the levels found in source plasma. The finished product fulfilled all purity requirements stated in the 4th edition of the European pharmacopeia.

Obteve-se concentrado de imunoglobulina G intravenosa IgGIV, altamente purificado, utilizando-se polietilenoglicol associado a uma única etapa de precipitação por etanol, em substituição ao tradicional método descrito por Cohn-Oncley, que emprega, em três etapas, o mesmo álcool resfriado, como agente precipitante. A purificação da fração bruta contendo mais de 95% de imunoglobulina G foi realizada utilizando-se cromatografia líquida com um trocador de cátion, a CM-Sepharose, como fase estacionária. Durante o processamento o produto foi submetido a dupla inativação viral sendo a primeira pela ação do caprilato de sódio, 30 mM a pH 5,1+/- 0,1 e a segunda por ação de mistura de solvente/detergente. O produto acabado foi formulado a 5% utilizando-se sucralose 10% como estabilizante. O rendimento da metodologia foi de 3,3g de IgG/litro de plasma. A análise do produto acabado demonstrou atividade anti-complementar inferior a 1CH50. O valor percentual de polímeros e agregados em cinco lotes realizados foi inferior a 3%. O estudo da capacidade de neutralização demonstrou a presença de anticorpos anti-bacterianos e anti-virais em concentração pelo menos três vezes maior que o plasma de origem. O produto acabado apresentou conformidade com todos os requisitos de pureza dispostos na farmacopéia européia IV edição.