Trasplante pulmonar: una perspectiva desde la inmunología / Lung transplantation: a perspective from immunology

Resumen El trasplante pulmonar implica una serie de desafíos, que como lo ha demostrado la historia, no sólo depende de un adecuado desarrollo de técnicas quirúrgicas, sino también de la comprensión de una serie de complejas interacciones inmunológicas celulares y humorales que serán las responsables del tipo de respuesta (innata y/o adquirida) fisiológica y que pudiesen desencadenar las complicaciones asociadas al trasplante (rechazo hiperagudo, agudo o crónico). Cada una de las cuales tiene su potencial prevención y/o tratamiento. El poder conocer esta serie de respuestas, permite al clínico anticiparse a algunos de estos eventos y evitar de mejor forma el daño y las consecuencias que pueden producir en los casos de trasplante pulmonar.

Lung transplantation involves a series of challenges, which as history has shown, depends not only on an adequate development of surgical techniques, but also on the understanding of a series of complex cellular and humoral immunological interactions that will be responsible for the type of physiological response (innate - acquired) and that could trigger the complications associated with transplantation (hyperacute, acute or chronic rejection). Each of which has its potential prevention and treatment. Being able to know this series of responses, allows the clinician to anticipate some of these events and to avoid in a better way the damage and the consequences that can occur in cases of lung transplantation.

Renal transplant patients with preformed anti-HLA antibodies: early biopsy findings and clinical outcomes / Pacientes transplantados renais com anticorpos anti-HLA pré-formados: achados precoces de biópsia e desfechos clínicos

Abstract Introduction: Renal fibrosis is the end point of a process that begins at transplant, with ischemia reperfusion and early inflammation, and progresses over time with immunological and non-immunological phenomena. Early identification of morphological markers and intervention could improve graft function and survival. Objective: to evaluate the correlation between intensity and specificity of pre-transplant anti-HLA antibodies and kidney allograft pathology in order to identify early risk factors or markers of allograft dysfunction. Methods: A retrospective cohort of kidney transplant recipients with pre-transplant anti-HLA antibodies who underwent graft biopsy within the first two years post-transplant was divided into two groups according to the specificity of anti-HLA antibodies: nonspecific (non-DSA, n = 29) and specific (DSA+, n = 16). Kidney graft pathology, renal function, and proteinuria were analyzed. Results: general characteristics were similar in both groups, except for the higher dose of thymoglobulin in DSA+ group (p < 0.05). The non-DSA group had higher scores for glomerulosclerosis, interstitial inflammation (i) and interstitial fibrosis (ci) (p < 0.05) and higher incidence of cell-mediated acute rejection. No statistical difference in incidence of antibody-mediated rejection, renal function, and proteinuria was observed during follow up. Discussion and conclusions: the difference in inflammation scores and interstitial fibrosis may be associated to the higher incidence of acute cell-mediated rejection and polyomavirus nephropathy in the Non-DSA group. We also should take into account the protective effect of higher doses of thymoglobulin, reducing ischemia reperfusion injury in the DSA+ group. The short follow-up might have been insufficient to detect long-term changes in allograft tissue, renal function, and proteinuria.

Resumo Introdução: A fibrose renal é o desfecho de um processo iniciado no transplante, com reperfusão, isquemia e inflamação precoce, que progride ao longo do tempo com fenômenos imunológicos e não imunológicos. A identificação de marcadores morfológicos e a intervenção precoce poderiam melhorar a função e a sobrevida do enxerto. Objetivo: Avaliar a correlação entre intensidade e especificidade de anticorpos anti-HLA pré-transplante alterações histológicas do enxerto renal, de forma a identificar fatores de risco ou marcadores de disfunção precoces do aloenxerto. Métodos: O presente estudo incluiu uma coorte retrospectiva de receptores de transplante renal sensibilizados com anticorpos anti-HLA no pré-transplante submetidos a biópsia de enxerto nos primeiros dois anos após o transplante. Os grupos foram divididos em função da especificidade dos anticorpos anti-HLA: sem anticorpos doador-específicos (não-DSA, n = 29) e com anticorpos doador-específicos (DSA+, n = 16). Alterações histológicas do enxerto renal, função renal e proteinúria foram analisados. Resultados: Os dois grupos tinham características gerais semelhantes, exceto pela dose mais elevada de timoglobulina administrada nos indivíduos do grupo DSA+ (p < 0,05). O grupo não-DSA teve escores mais elevados de glomeruloesclerose, inflamação intersticial (i) e fibrose intersticial (ci) (p < 0,05), além de maior incidência de rejeição celular aguda (RCA). Não foi observada diferença estatística na incidência de rejeição mediada por anticorpos, função renal ou proteinúria durante o seguimento. Discussão e Conclusões: A diferença nos escores de inflamação e fibrose intersticial pode estar associada à maior incidência de RCA e nefropatia por poliomavírus no grupo não-DSA. Devemos considerar ainda o efeito protetor das doses mais elevadas de timoglobulina na redução da lesão por isquemia-reperfusão no grupo DSA+. O curto período de seguimento pode ter sido insuficiente para detectar alterações de longo prazo no tecido do aloenxerto, função renal e proteinúria.

Immunosuppressive mechanism of Hypoderma lineatum secreted serine esterase, a potential modulatory method used to inhibit transplant rejection

Background: Although immunosuppressive therapies have made organ transplantation a common medical procedure worldwide, chronic toxicity has a major issue for long-term treatment. One method to improve therapies and methods is the application of immunomodulatory agents from parasites such as Hypoderma lineatum. Hypodermin A (HA) is a serine esterase secreted by the larvae of Hypoderma lineatum, several studies demonstrated its immunosuppressive mechanism in vitro, and recently we discovered that HA inhibits the expression of interferon (IFN)-γ and interleukin (IL)-2 and activates IL-10 expression. Therefore, we hypothesized that it might be a potential agent used to block allograft rejections. However, most studies of the immunosuppressive mechanisms associated with HA were undertaken at the cellular level. In order to augment these studies, we evaluated the immunosuppressive effects of HA in vivo using an HA transgenic mouse model. Result: Our results revealed similar findings to those reported by in vitro studies, specifically that HA induced prostaglandin E2 expression, downregulated IFN-γ and IL-2 expression, and promoted IL-10 secretion via E-type prostanoid receptor 4. Additionally, we observed that HA overexpression inhibited lipopolysaccharide-induced TLR4 activation. These findings provide insight into a new potential agent capable of blocking graft rejection. Conclusion: Our founding suggested that HA-related treatment could be a promising option to improve the viability of grafts in human.

Heart Transplantation for Peripartum Cardiomyopathy: A Single-Center Experience / Transplante Cardíaco por Cardiomiopatia Periparto: Uma Experiência de Centro Único

Abstract Background: Peripartum cardiomyopathy is an idiopathic disorder defined by the occurrence of acute heart failure during late pregnancy or post-partum period in the absence of any other definable cause. Its clinical course is variable and severe cases might require heart transplantation. Objective: To investigate long-term outcomes after heart transplantation (HT) for peripartum cardiomyopathy (PPCM). Methods: Out of a single-center series of 1938 HT, 14 HT were performed for PPCM. We evaluated clinical characteristics, transplant-related complications, and long-term outcomes, in comparison with 28 sex-matched controls. Primary endpoint was death from any cause; secondary endpoints were transplant-related complications (rejection, infection, cardiac allograft vasculopathy). A value of p < 0.05 was considered of statistical significance. Results: PPCM patients and matched controls were comparable for most variables (all p values > 0.05), except for a higher use of inotropes at the time of HT in PPCM group (p = 0.03). During a median follow-up of 7.7 years, 16 patients died, 3 (21.5%) in PPCM group and 13 (46.5%) in control group. Mortality was significantly lower in PPCM group (p = 0.03). No significant difference was found in terms of transplant-related complications (p > 0.05). Conclusions: Long-term outcomes following HT for PPCM are favorable. Heart transplantation is a valuable option for PPCM patients who did not recover significantly under medical treatment.

Resumo Fundamento: A cardiomiopatia periparto é uma doença idiopática definida pela ocorrência de insuficiência cardíaca aguda durante a gravidez tardia ou pós-parto na ausência de qualquer outra causa definível. Seu curso clínico é variável e casos graves podem exigir transplante. cardíaco. Objetivo: Pesquisar os resultados a longo prazo após transplante cardíaco (TC) por cardiomiopatia periparto (CMPP). Métodos: De uma única série central de 1938 TC, 14 TC foram realizados por CMPP. Foram avaliadas características clínicas, complicações relacionadas ao transplante e resultados a longo prazo, em comparação com 28 controles pareados por gênero. O principal critério de avaliação foi a morte por qualquer causa; os critérios secundários foram complicações relacionadas ao transplante (rejeição, infecção, vasculopatia do aloenxerto cardíaco). Um valor de p < 0,05 foi considerado estatisticamente significante. Resultados: As pacientes com CMPP e controles pareados foram comparáveis ​​para a maioria das variáveis (todos os valores de p > 0,05), exceto para um maior uso de inotrópicos no momento do TC no grupo CMPP (p = 0,03). Durante um seguimento médio de 7,7 anos, 16 pacientes morreram, 3 (21,5%) no grupo CMPP e 13 (46,5%) no grupo controle. A mortalidade foi significativamente menor no grupo CMPP (p = 0,03). Não foram encontradas diferenças significativas em termos de complicações relacionadas ao transplante (p> 0,05). Conclusões: Os resultados a longo prazo após TC para CMPP são favoráveis. O transplante cardíaco é uma opção valiosa para pacientes com CMPP que não se recuperaram significativamente sob tratamento médico.

Description and evaluation of experimental models for uterine transplantation in pigs / Descrição e avaliação de modelos experimentais para transplante uterino em suínos

ABSTRACT Objective: To evaluate the technique of uterine transplantation and the use of drugs used in the process of immunosuppression. Methods: We included 12 sows, and immunosuppression was performed with minimal doses of cyclosporine, and cross-match was done to exclude the possibility of blood incompatibility. Hysterectomy was performed in the donor under general anesthesia, with the removal of the aorta and inferior vena cava in monobloc, and anastomosis of these vessels was made in the recipient. Results: Six experiments were performed, and on the immediate postoperative period, five animals had good reperfusion. However, on the seventh postoperative day, histological analysis showed rejection in five animals. Conclusion: The experimental model of uterine transplantation is feasible, but monitoring doses of immunosuppressants is pivotal to prevent rejection episodes.

RESUMO Objetivo: Avaliar a técnica de transplante uterino e o uso de drogas no processo de imunossupressão. Métodos: Foram incluídas 12 porcas, sendo realizada imunossupressão com doses mínimas de ciclosporina, e prova cruzada para afastar a possibilidade de incompatibilidade sanguínea. Realizou-se, na doadora, histerectomia sob anestesia geral, com a retirada, em monobloco, da aorta e da veia cava inferior, de tal forma que, na receptora, fosse possível realizar a anastomose com estes vasos. Resultados: Foram realizados seis experimentos e, no pós-operatório imediato, houve boa reperfusão em cinco animais. Entretanto, no sétimo dia de pós-operatório, as análises histológicas demonstraram rejeição em cinco deles. Conclusão: O modelo experimental de transplante uterino é factível, mas a monitorização das doses de imunossupressores é importante, a fim de impedir os episódios de rejeição.

Conversion to Mycophenolate Mofetil Monotherapy in Liver Recipients: Calcineurin Inhibitor Levels are Key

Abstract: The use of calcineurin inhibitors (CNI) after liver transplantation is associated with post-transplant nephrotoxicity. Conversion to mycophenolate mofetil (MMF) monotherapy improves renal function, but is related to graft rejection in some recipients. Our aim was to identify variables associated with rejection after conversion to MMF monotherapy. Conversion was attempted in 40 liver transplant recipients. Clinical variables were determined and peripheral mononuclear blood cells were immunophenotyped during a 12-month follow- up. Conversion was classified as successful (SC) if rejection did not occur during the follow-up. MMF conversion was successful with 28 patients (70%) and was associated with higher glomerular filtration rates at the end of study. It also correlated with increased time elapsed since transplantation, low baseline CNI levels (Tacrolimus ≤ 6.5 ng/mL or Cyclosporine ≤ 635 ng/mL) and lower frequency of tacrolimus use. The only clinical variable independently related to SC in multivariate analysis was low baseline CNI levels (p = 0.02, OR: 6.93, 95%, CI: 1.3-29.7). Mean baseline fluorescent intensity of FOXP3+ T cells was significantly higher among recipients with SC. In conclusion, this study suggests that baseline CNI levels can be used to identify recipients with higher probability of SC to MMF monotherapy. Clinicaltrials.gov identification: NCT01321112.

Prognostic factors for the evolution and reversibility of chronic rejection in pediatric liver transplantation

OBJECTIVE: Chronic rejection remains a major cause of graft failure with indication for re-transplantation. The incidence of chronic rejection remains high in the pediatric population. Although several risk factors have been implicated in adults, the prognostic factors for the evolution and reversibility of chronic rejection in pediatric liver transplantation are not known. Hence, the current study aimed to determine the factors involved in the progression or reversibility of pediatric chronic rejection by evaluating a series of chronic rejection cases following liver transplantation. METHODS: Chronic rejection cases were identified by performing liver biopsies on patients based on clinical suspicion. Treatment included maintaining high levels of tacrolimus and the introduction of mofetil mycophenolate. The children were divided into 2 groups: those with favorable outcomes and those with adverse outcomes. Multivariate analysis was performed to identify potential risk factors in these groups. RESULTS: Among 537 children subjected to liver transplantation, chronic rejection occurred in 29 patients (5.4%). In 10 patients (10/29, 34.5%), remission of chronic rejection was achieved with immunosuppression (favorable outcomes group). In the remaining 19 patients (19/29, 65.5%), rejection could not be controlled (adverse outcomes group) and resulted in re-transplantation (7 patients, 24.1%) or death (12 patients, 41.4%). Statistical analysis showed that the presence of ductopenia was associated with worse outcomes (risk ratio=2.08, p=0.01). CONCLUSION: The presence of ductopenia is associated with poor prognosis in pediatric patients with chronic graft rejection.

Hospitalizations for cardiovascular diseases and the coverage by the family health strategy / Internações por doenças cardiovasculares e a cobertura da estratégia saúde da família / Internaciones por enfermedades cardiovasculares y la cobertura de la estrategia salud de la familia

AbstractObjective: to verify the correlation between the rates of hospitalization for primary care-sensitive cardiovascular diseases and the coverage by the Family Health Strategy of residents of the State of Paraná, by regional health divisions, from 2000 to 2011.Method: ecological study developed from data of the Hospital Information System of the Brazilian Unified Health System (SUS) and the Department of Primary Care of the Ministry of Health. The rates of hospitalization for cardiovascular diseases were correlated with the annual coverage by the Family Health Strategy using Pearson's and Spearman's correlation coefficients.Result: there was a strong and negative correlation in the State of Paraná (r=-0.91; p <0.001) and in most regional health divisions, with the highest correlations observed in the Metropolitan and Toledo (r =-0.93; p<0.001) and Paranaguá (r=-0.92, p<0.001) regional health divisions.Conclusion: the results suggest that the increase in the coverage by the Family Health Strategy was an important factor for decrease in the hospitalizations for cardiovascular conditions among residents of the State of Paraná and in most regional health divisions. Other studies should be performed to analyze the factors and causes in regional health divisions where there was no correlation with increase in the Family Health Strategy.

ResumoObjetivo:verificar a correlação entre taxas de internação por doenças cardiovasculares sensíveis à atenção primária e a cobertura da Estratégia Saúde da Família de residentes no estado do Paraná, por regionais de saúde, no período de 2000 a 2011.Método:estudo ecológico, desenvolvido a partir de dados do Sistema de Informações Hospitalares do Sistema Único de Saúde e do Departamento de Atenção Básica do Ministério da Saúde. Correlacionaram-se as taxas de internação por doenças cardiovasculares com as coberturas anuais da Estratégia Saúde da Família, utilizando-se os coeficientes de correlação de Pearson e Spearman.Resultado:houve correlação negativa e forte no estado do Paraná (r=-0,91; p<0,001) e na maioria das regionais de saúde, sendo maior na Metropolitana e Toledo (r=-0,93; p<0,001) e Paranaguá (r=-0,92; p<0,001).Conclusão:os resultados sugerem que o aumento da cobertura da Estratégia Saúde da Família foi fator importante para a diminuição das internações por condições cardiovasculares em residentes no estado do Paraná e na maioria das regionais de saúde. Outros estudos devem ser realizados para analisar fatores e causas nas regiões do estado onde não houve correlação com incremento da Estratégia Saúde da Família.

ResumenObjetivo:verificar la correlación entre tasas de internación por enfermedades cardiovasculares sensibles a la atención primaria y la cobertura de la Estrategia Salud de la Familia de residentes en el estado de Paraná, por regionales de salud, en el período de 2000 a 2011.Método:estudio ecológico, desarrollado a partir de datos del Sistema de Informaciones Hospitalarias del Sistema Único de Salud y del Departamento de Atención Básica del Ministerio de la Salud. Se correlacionaron las tasas de internación por enfermedades cardiovasculares con las coberturas anuales de la Estrategia Salud de la Familia, utilizando los coeficientes de correlación de Pearson y Spearman.Resultado:hubo correlación negativa y fuerte en el estado de Paraná (r=-0,91; p<0,001) y en la mayoría de las regionales de salud, siendo mayor en la Metropolitana y Toledo (r=-0,93; p<0,001) y Paranaguá (r=-0,92; p<0,001).Conclusión:los resultados sugieren que el aumento de la cobertura de la Estrategia Salud de la Familia fue un factor importante para la disminución de las internaciones por condiciones cardiovasculares en residentes en el estado de Paraná y en la mayoría de las regionales de salud. Otros estudios deben ser realizados para analizar factores y causas en las regiones del estado en donde no hubo correlación con incremento de la Estrategia Salud de la Familia.

Cultural adaptation to Brazilian Portuguese of the Face, Legs, Activity, Cry, Consolability revised (FLACCr) scale of pain assessment / Adaptação cultural para o português do Brasil da escala de avaliação de dor Face, Legs, Activity, Cry, Consolability revised(FLACCr) / Adaptación cultural para el portugués de Brasil de la escala de evaluación del dolor Face, Legs, Activity, Cry, Consolability revised(FLACCr)

AbstractObjective: to perform the translation into Brazilian Portuguese and cultural adaptation of the Face, Legs, Activity, Cry, Consolability revised (FLACCr) scale, with children under 18 years old, affected by cerebral palsy, presenting or not cognitive impairment and unable to report their pain.Method: methodological development study of translation into Portuguese and cultural adaptation of the FLACCr. After approval by the ethics committee, the process aimed at translation and back-translation, evaluation of translation and back-translation using the Delphi technique and assessment of cultural equivalence. The process included the five categories of the scale and the four application instructions, considering levels of agreement equal to or greater than 80%.Results: it was necessary three rounds of the Delphi technique to achieve consensus among experts. The agreement achieved for the five categories was: Face 95.5%, Legs 90%, Activity 94.4%, Cry 94.4% and Consolability 99.4%. The four instructions achieved the following consensus levels: 1st 99.1%, 2nd 99.2%, 3rd 99.1% and 4th 98.3%.Conclusion: the method enabled the translation and cultural adaptation of the FLACCr. This is a study able to expand the knowledge of Brazilian professionals on pain assessment in children with CP.

ResumoObjetivo:realizar a tradução para a língua portuguesa do Brasil e adaptação cultural da escala Face, Legs, Activity, Cry, Consolability revised(FLACCr), com crianças de até 18 anos de idade, acometidas por paralisia cerebral, apresentando ou não comprometimento cognitivo e impossibilitadas de relatar sua dor.Método:estudo de desenvolvimento metodológico de tradução para o português e adaptação cultural da FLACCr. Após aprovação do comitê de ética, o processo contemplou tradução e retrotradução, avaliação da tradução e da retrotradução utilizando a técnica de Delphi e avaliação da equivalência cultural. O processo incluiu as cinco categorias da escala e as quatro orientações de aplicação, considerando nível de concordância igual ou maior a 80%.Resultados:foram necessários três ciclos da técnica de Delphi para consenso entre os juízes. A concordância obtida para as cinco categorias foi: Face 95,5%, Pernas 90%, Atividade 94,4%, Choro 94,4% e Consolabilidade 99,4%. As quatro orientações alcançaram os seguintes níveis de consenso: 1ª 99,1%, 2ª 99,2%, 3ª 99,1% e 4ª 98,3%.Conclusão:o método possibilitou o desenvolvimento da tradução e adaptação cultural da FLACCr. Sendo um estudo capaz de ampliar o conhecimento de profissionais brasileiros sobre a avaliação da dor em crianças com PC.

ResumenObjetivo:realizar la traducción para el portugués de Brasil y la adaptación cultural de la escala, Face, Legs, Activity, Cry, Consolability revised(FLACCr), con niños menores de 18 años de edad, afectados por la parálisis cerebral, presentando o no deterioro cognitivo y que no pueden comunicar su dolor.Método:estudio de desarrollo metodológico de traducción al portugués y adaptación cultural de la FLACCr. Después de la aprobación por el comité de ética, el proceso incluyó la traducción y retrotraducción, evaluación de la traducción y retrotraducción utilizando la técnica Delphi y evaluación de la equivalencia cultural. El proceso incluyó las cinco categorías de la escala y las cuatro orientaciones de aplicación, teniendo en cuenta nivel de concordancia igual o superior al 80%.Resultados:fueron necesarios tres ciclos de la técnica Delphi para el consenso entre los jueces. La concordancia obtenida para las cinco categorías fue: Cara 95,5%, Piernas 90%, Actividad 94,4%, Llanto 94,4% y Capacidad de Consuelo 99,4%. Las cuatro orientaciones alcanzaron los siguientes niveles de consenso: 1ª 99,1%, 2ª 99,2%, 3ª 99,1% y 4ª 98,3%.Conclusión:el método permitió el desarrollo de la traducción y adaptación cultural de la FLACCr. Este estudio fue capaz de aumentar el conocimiento de los profesionales brasileños en la evaluación del dolor en niños con PC.

Meaning of leprosy for people who have experienced treatment during the sulfonic and multidrug therapy periods / Significado da hanseníase para pessoas que viveram o tratamento no período sulfônico e da poliquimioterapia / Significado de la lepra para personas que experimentaron el tratamiento en el período sulfónico y de poliquimioterapia

AbstractObjective: to analyze the meanings of leprosy for people treated during the sulfonic and multidrug therapy periods.Method: qualitative nature study based on the Vigotski's historical-cultural approach, which guided the production and analysis of data. It included eight respondents who have had leprosy and were submitted to sulfonic and multidrug therapy treatments. The participants are also members of the Movement for Reintegration of People Affected by Leprosy.Results: the meanings were organized into three meaning cores: spots on the body: something is out of order; leprosy or hanseniasis? and leprosy from the inclusion in the Movement for Reintegration of People Affected by Leprosy.Conclusion: the meanings of leprosy for people submitted to both regimens point to a complex construction thereof, indicating differences and similarities in both treatments. Health professionals may contribute to the change of the meanings, since these are socially constructed and the changes are continuous.

ResumoObjetivo:analisar significados da hanseníase para as pessoas que foram tratadas no período sulfônico e no período da poliquimioterapia.Método:estudo de natureza qualitativa fundamentado na abordagem histórico-cultural de Vigotski, a qual orientou a construção e análise dos dados. Foram incluídos oito entrevistados que já tiveram hanseníase e que realizaram tratamento no período sulfônico e da poliquimioterapia, sendo participantes do Movimento de Reintegração das Pessoas Atingidas pela Hanseníase.Resultados:os significados foram organizados em três núcleos de significação: manchas no corpo: alguma coisa está fora de ordem; lepra ou hanseníase? e hanseníase a partir da inserção no Movimento de Reintegração das Pessoas Atingidas pela Hanseníase.Conclusão:os significados de hanseníase para pessoas tratadas nos dois períodos apontam para a construção complexa dos mesmos, indicando diferenças e semelhanças nos dois períodos. Os profissionais de saúde podem contribuir para a mudança de significados, pois esses são socialmente construídos e as transformações são contínuas.

ResumenObjetivo:analizar los significados de la lepra para las personas que fueron tratadas en el período sulfónico y en el período de poliquimioterapia.Método:estudio de naturaleza cualitativa fundamentado en el abordaje histórico cultural de Vygotsky, el cual orientó la construcción y análisis de los datos. Fueron incluidos ocho entrevistados que ya tuvieron lepra y que realizaron tratamiento en el período sulfónico y de poliquimioterapia, siendo participantes del Movimiento de Reintegración de Personas Afectadas por la Lepra.Resultados:los significados fueron organizados en tres núcleos de significación: manchas en el cuerpo: alguna cosa está fuera de orden; ¿Lepra o enfermedad de Hansen?; y lepra a partir de la inserción en el Movimiento de Reintegración de Personas Afectadas por la Lepra. Conclusión: los significados de la lepra para las personas tratadas en los dos períodos apuntan para la construcción compleja de los mismos, indicando diferencias y semejanzas en los dos períodos. Los profesionales de la salud pueden contribuir para el cambio de significados, ya que estos son socialmente construidos y las transformaciones son continuas.

Instrument to assess the nursing care product: development and content validation / Instrumento para avaliação do produto do cuidar em enfermagem: desenvolvimento e validação de conteúdo / Instrumento para evaluación del producto del cuidar en enfermería: desarrollo y validación de contenido

AbstractObjectives: develop and validate the content of a tool about nursing care production.Method: the data were collected between 2011 and 2013, based on focus groups, the application of semistructured questionnaires (prototype test) and the Delphi technique. The focus groups were used to produce the instrument items and held at three hospitals in the interior of the State of São Paulo, involving 20 nurses. A panel of 10 experts evaluated the instrument.Results: after two phases of the Delphi technique, the tool consisted of eight items. The content validity index of the scale corresponded to ≥0.9 and the content validity of the items ranged between 0.8 and 1.0, indicating the maintenance of the structure and content. The assertion on the applicability in daily nursing practice showed a content validity index of the scale equal to 0.8.Conclusion: this study permitted the development and content validation of scale on nursing care production, equipping the nurses in their management practice.

ResumoObjetivos:desenvolver e validar o conteúdo de um instrumento sobre produção do cuidado de enfermagem.Método:a coleta de dados ocorreu entre 2011 e 2013, a partir de grupos focais, aplicação de questionários semiestruturados (teste do protótipo) e técnica Delphi. Os grupos focais foram utilizados para geração de itens do instrumento e realizados em três hospitais do interior do Estado de São Paulo, com a participação de 20 enfermeiros. A apreciação do instrumento foi conduzida por um painel de 10 especialistas.Resultados:após duas fases da técnica Delphi, o instrumento passou a ser constituído por oito itens. O índice de validade do conteúdo da escala foi de ≥0,9 e a validade dos conteúdos dos itens apresentou variação de 0,8 a 1,0, indicando a manutenção da estrutura e do conteúdo. A afirmativa referente à aplicabilidade na prática diária do enfermeiro apresentou índice de validade do conteúdo da escala de 0,8.Conclusão:este estudo possibilitou desenvolver e validar o conteúdo de uma escala sobre produção do cuidado de enfermagem, instrumentalizando os enfermeiros em sua prática gerencial.

ResumenObjetivos:desarrollar y validar el contenido de un instrumento sobre producción del cuidado de enfermería.Método:los datos fueron recolectados entre 2011 y 2013, a partir de grupos focales, aplicación de cuestionarios semiestructurados (prueba del prototipo) y técnica Delphi. Los grupos focales fueron utilizados para generar ítems del instrumento y organizados en tres hospitales del interior del Estado de São Paulo, con la participación de 20 enfermeros. La apreciación del instrumento fue conducida por un panel de 10 especialistas.Resultados:tras dos fases de la técnica Delphi, el instrumento pasó a ser constituido por ocho ítems. El índice de validez de contenido de la escala fue ≥0,9 y la validez de los contenidos mostró variación de 0,8 a 1,0, indicando la manutención de la estructura y del contenido. La afirmativa respecto a la aplicabilidad en la práctica diaria del enfermero mostró índice de validez del contenido de la escala de 0,8.Conclusión:este estudio permitió desarrollar y validar el contenido de una escala sobre producción del cuidado de enfermería, instrumentalizando los enfermeros en su práctica gerencial.

Foot reflexology in feet impairment of people with type 2 diabetes mellitus: randomized trial / Reflexologia podal no comprometimento dos pés de pessoas com diabetes mellitus tipo 2: ensaio randomizado / Reflexología podal en el comprometimiento de los pies de personas con diabetes mellitus tipo 2: ensayo aleatorio

AbstractObjective: to evaluate the effect of foot reflexology on feet impairment of people with type 2 diabetes mellitus.Method: this is a randomized, controlled and blind clinical trial. The sample was comprised by people with type 2 diabetes mellitus who, after being randomized into Treated group (n = 21) and Control group (n = 24), received guidelines on foot self-care. To the Treated Group it was also provided 12 sessions of foot reflexology. The scores of impairment indicators related to skin and hair, blood circulation, tissue sensitivity and temperature were measured by means of the instrument for assessing tissue integrity of the feet of people with diabetes mellitus. Chi-square test, Fisher exact test, Mann-Whitney test and regression analyzes were applied to the data, considering a significance level of 5% (P value <0.05).Results: participants who received the therapy showed better scores in some impairment indicators related to skin and hair (hair growth, elasticity/turgor, hydration, perspiration, texture and integrity of the skin/ skin peeling).Conclusion: the foot reflexology had a beneficial effect on feet impairment of people with type 2 diabetes mellitus, which makes it a viable therapy, deserving investment. This study was registered in the Brazilian Registry of Clinical Trials - RBR-8zk8sz.

ResumoObjetivo:avaliar o efeito da reflexologia podal no comprometimento dos pés de pessoas com diabetes mellitus tipo 2.Método:trata-se de um ensaio clínico, randomizado, controlado e mascarado. A amostra foi composta por pessoas com diabetes mellitus tipo 2 que, após serem randomizadas em grupo Tratado (n=21) e Controle (n=24), receberam orientações de autocuidado com os pés. Ao Grupo Tratado também foram fornecidas 12 sessões de reflexologia podal. Foram mensurados os escores de comprometimento de indicadores relacionados à pele e pelos, circulação sanguínea, sensibilidade e temperatura tissular por meio do Instrumento para avaliação da integridade tissular dos pés de pessoas com diabetes mellitus. Aos dados foram aplicados os testes Qui-Quadrado, Exato de Fisher, Mann-Whitney e Análises de regressão, considerando-se nível de significância de 5% (Valor P<0,05).Resultados:os participantes que receberam a terapia apresentaram melhores escores de comprometimento em alguns indicadores relacionados à pele e pelos (crescimento de pelos, elasticidade/tugor, hidratação, transpiração, textura e integridade da pele/descamação cutânea).Conclusão:a reflexologia podal apresentou efeito benéfico sobre o comprometimento dos pés de pessoas com diabetes mellitus tipo 2, o que a torna uma terapia viável e que merece investimento. Este estudo foi registrado no Registro Brasileiro de Ensaios Clínicos - RBR-8zk8sz.

ResumenObjetivo:evaluar el efecto de la reflexología podal en el comprometimiento de los pies de personas con diabetes mellitus tipo 2.Método:se trata de un ensayo clínico, aleatorio, controlado y enmascarado. La muestra estuvo compuesta por personas con diabetes mellitus tipo 2 que, después de ser tratadas aleatoriamente en los grupos Tratado (n=21) y Control (n=24), recibieron orientaciones de autocuidado de los pies. También, al Grupo Tratado se le suministraron 12 sesiones de reflexología podal. Fueron medidos los puntajes de comprometimiento de indicadores relacionados a la piel y pelos, circulación sanguínea, sensibilidad y temperatura tisular por medio de instrumento para evaluación de la integridad del tejido de los pies de personas con diabetes mellitus. Los datos fueron sometidos a las pruebas Chi-cuadrado, Exacta de Fisher, Mann-Whitney y Análisis de regresión, considerando un nivel de significación de 5% (Valor p<0,05).Resultados:los participantes que recibieron la terapia presentaron mejores puntajes de comprometimiento en algunos indicadores relacionados a la piel y pelos (crecimiento de pelos, elasticidad/turgencia, hidratación, transpiración, textura e integridad de la piel/descamación cutánea).Conclusión:la reflexología podal presentó efecto benéfico sobre el comprometimiento de los pies de personas con diabetes mellitus tipo 2, lo que la torna una terapia viable y que merece inversiones. Este estudio fue registrado en el Registro Brasileño de Ensayos Clínicos - RBR-8zk8sz.

Assessment of nursing care using indicators generated by software / Avaliação da assistência de enfermagem utilizando indicadores gerados por um software / Evaluación de la asistencia de enfermería utilizando indicadores generados por un software

OBJECTIVE: to analyze the efficacy of the Nursing Process in an Intensive Care Unit using indicators generated by software. METHOD: cross-sectional study using data collected for four months. RNs and students daily registered patients, took history (at admission), performed physical assessments, and established nursing diagnoses, nursing plans/prescriptions, and assessed care delivered to 17 patients using software. Indicators concerning the incidence and prevalence of nursing diagnoses, rate of effectiveness, risk diagnoses, and rate of effective prevention of complications were computed. RESULTS: the Risk for imbalanced body temperature was the most frequent diagnosis (23.53%), while the least frequent was Risk for constipation (0%). The Risk for Impaired skin integrity was prevalent in 100% of the patients, while Risk for acute confusion was the least prevalent (11.76%). Risk for constipation and Risk for impaired skin integrity obtained a rate of risk diagnostic effectiveness of 100%. The rate of effective prevention of acute confusion and falls was 100%. CONCLUSION: the efficacy of the Nursing Process using indicators was analyzed because these indicators reveal how nurses have identified patients' risks and conditions, and planned care in a systematized manner. .

OBJETIVO: analisar a eficácia do Processo de Enfermagem em uma Unidade de Terapia Intensiva, utilizando indicadores gerados por um software. MÉTODO: estudo transversal, cujos dados foram coletados durante quatro meses. Enfermeiros e acadêmicos realizaram, diariamente, cadastro e anamnese (na admissão), exame físico, diagnósticos de enfermagem, planejamento/prescrição de enfermagem e avaliação da assistência de 17 pacientes, utilizando um software. Calculou-se os indicadores incidência e prevalência de diagnósticos de enfermagem, taxa de efetividade diagnóstica de risco e taxa de efetividade na prevenção de complicações. RESULTADOS: o Risco de desequilíbrio na temperatura corporal foi o diagnóstico mais incidente (23,53%) e o menos incidente foi o Risco de constipação (0%). O Risco de integridade da pele prejudicada foi prevalente em 100% dos pacientes, enquanto o Risco de confusão aguda foi o menos prevalente (11,76%). Risco de constipação e Risco de integridade da pele prejudicada obtiveram taxa de efetividade diagnóstica de risco de 100%. A taxa de efetividade na prevenção de confusão aguda e de queda foi de 100%. CONCLUSÃO: analisou-se a eficácia do Processo de Enfermagem utilizando indicadores, pois retratam como o enfermeiro tem identificado os problemas e riscos do paciente, e planejado a assistência de forma sistematizada. .

OBJETIVO: analizar la eficacia del Proceso de Enfermería en una Unidad de Terapia Intensiva, utilizando indicadores generados por un software. MÉTODO: estudio transversal, cuyos datos fueron recolectados durante cuatro meses. Enfermeros y académicos realizaron, diariamente, registro y anamnesis (en la admisión), examen físico, diagnósticos de enfermería, planificación/prescripción de enfermería y evaluación de la asistencia en 17 pacientes, utilizando un software. Se calculó los indicadores incidencia y prevalencia de diagnósticos de enfermería, la tasa de efectividad diagnóstica de riesgo y la tasa de efectividad en la prevención de complicaciones. RESULTADOS: el Riesgo de desequilibrio en la temperatura corporal fue el diagnóstico más prevalente (23,53%) y el menos prevalente fue el Riesgo de constipación (0%). El Riesgo de integridad de la piel perjudicada fue prevalente en 100% de los pacientes, en cuanto el Riesgo de confusión aguda fue el menos prevalente (11,76%). El Riesgo de constipación y el Riesgo de integridad de la piel perjudicada obtuvieron una tasa de efectividad diagnóstica de riesgo de 100%. La tasa de efectividad en la prevención de confusión aguda y de caída fue de 100%. CONCLUSIÓN: se analizó la eficacia del Proceso de Enfermería utilizando indicadores, ya que retratan cómo el enfermero ha identificado los problemas y riesgos del paciente, y planificado la asistencia de forma sistematizada. .

Subdominant H60 antigen-specific CD8 T-cell response precedes dominant H4 antigen-specific response during the initial phase of allogenic skin graft rejection

In allogeneic transplantation, including the B6 anti-BALB.B settings, H60 and H4 are two representative dominant minor histocompatibility antigens that induce strong CD8 T-cell responses. With different distribution patterns, H60 expression is restricted to hematopoietic cells, whereas H4 is ubiquitously expressed. H60-specific CD8 T-cell response has been known to be dominant in most cases of B6 anti-BALB.B allo-responses, except in the case of skin transplantation. To understand the mechanism underlying the subdominance of H60 during allogeneic skin transplantation, we investigated the dynamics of the H60-specific CD8 T cells in B6 mice transplanted with allogeneic BALB.B tail skin. Unexpectedly, longitudinal bioluminescence imaging and flow cytometric analyses revealed that H60-specific CD8 T cells were not always subdominant to H4-specific cells but instead showed a brief dominance before the H4 response became predominant. H60-specific CD8 T cells could expand in the draining lymph node and migrate to the BALB.B allografts, indicating their active participation in the anti-BALB.B allo-response. Enhancing the frequencies of H60-reactive CD8 T cells prior to skin transplantation reversed the immune hierarchy between H60 and H4. Additionally, H60 became predominant when antigen presentation was limited to the direct pathway. However, when antigen presentation was restricted to the indirect pathway, the expansion of H60-specific CD8 T cells was limited, whereas H4-specific CD8 T cells expanded significantly, suggesting that the temporary immunodominance and eventual subdominance of H60 could be due to their reliance on the direct antigen presentation pathway. These results enhance our understanding of the immunodominance phenomenon following allogeneic tissue transplantation.

Increase in Anti-Gal IgM Level is Associated With Early Graft Failure in Intraportal Porcine Islet Xenotransplantation

BACKGROUND: Anti-Gal is a major antibody induced in non-human primates (NHPs) after xenotransplantation. To understand the mechanism of graft rejection, we investigated the association between anti-Gal responses and graft failure in NHP recipients of porcine islet transplantation (PITx). METHODS: Intraportal PITx was performed in 35 diabetic NHPs, and graft function was monitored. Early graft failure (EGF) was defined as loss of graft function within a month after PITx. Seven, 19, nine NHPs received immunosuppression (IS) without CD40 pathway blockade (Group I), with anti-CD154 (Group II), and with anti-CD40 (Group III), respectively. The anti-Gal levels on day 0 and day 7 of PITx were measured by ELISA. RESULTS: The frequency of EGF was significantly lower in Group II (26.3%) than in Group I (100%, P=0.0012) and Group III (77.8%, P=0.0166). While levels of anti-Gal IgG in Group I and anti-Gal IgM in Group III increased on day 7 compared with day 0 (P=0.0156 and 0.0273), there was no increase in either on day 7 in Group II. The ratio of anti-Gal IgM or IgG level on day 7 to that on day 0 (Ratio7/0) was significantly higher in recipients with EGF than without EGF (P=0.0009 and 0.0027). ROC curve analysis of anti-Gal IgM Ratio7/0 revealed an area under the curve of 0.789 (P=0.0003). CONCLUSIONS: IS with anti-CD154 suppressed anti-Gal responses and prevented EGF in PITx. Anti-Gal IgM Ratio7/0, being associated with EGF, is a predictive marker for EGF.

Limited immune tolerance induced by transient mixed chimerism

No abstract available.

Development of dog mammary tumor xenograft in immunosuppressed Swiss albino mice.

Development and study of dog mammary tumour xenograft in immunosuppressed Swiss Albino Mice adds a new dimension in cancer research as dog tumors have many similarities with human tumors regarding progression, histopathology, molecular mechanism, immune response and therapy. Failure of the immune system to recognize and eliminate cancer cells leads to cancer progression and the fight between immune cells and cancer cells has a great role in understanding the mechanism of cancer progression and elimination. Rejection and acceptance of tumour xenograft depends on efficiency of CD4+, CD8+ and NK cell populations. In the present investigation, dog mammary tumor xenograft in cyclosporine-A and γ-irradiated, immunosuppressed Swiss Albino mice was developed and the immune cell status of graft accepted and rejected mice was assessed. It was observed that all the major immune cells (CD4+, CD8+ and NK cells) play an equal role in tumour rejection.

Trasplante renal en pacientes con anticuerpos dirigidos contra donante

En trasplante renal, los anticuerpos donante-específicos por ensayos de fase sólida predicen el rechazo temprano mediado por anticuerpos, incluso con resultados negativos de citometría de flujo o citotoxicidad dependiente del complemento. Aquí se describen los protocolos de inmunosupresión y los resultados a diez meses de cuatro pacientes en los que se detectó anticuerpos donante-específicos anti-antígenos leucocitarios humanos (HLA) por Luminex®, pero no detectados por el método de citotoxicidad dependiente de complemento (CDC) ni por citometría de flujo. Los cuatro pacientes recibieron tratamiento de inducción con 5 dosis de timoglobulina de 1.25 mg/kg y 5 dosis de inmunoglobulina intravenosa (IVIG) de 400 mg/kg. Además, uno recibió 20 mg de basiliximab el mismo día del trasplante y el día 4 postrasplante; otro recibió 3 sesiones de plasmaféresis en los días -5, -3, y -1 y eculizumab en dosis de 1200 mg antes del trasplante, 900 mg el día 1, and 600 mg por semana durante un mes. En todos los casos, la inmunosupresión de mantenimiento consistió en tacrolimus, micofenolato y deltisona. Todos presentaron buenos resultados en el corto plazo. Nuestra experiencia sugiere que los pacientes con anticuerpos donante-específicos anti-HLA detectados solo por Luminex® deben recibir un seguimiento estricto y que en esta población se pueden obtener buenos resultados a partir del uso de terapia de inducción con timoglobulina e IVIG.

In renal transplantation, donor specific antibodies (DSAs) detected by sensitive solid-phase assay foresee early antibody-mediated rejections, even with negative complement-dependent cytotoxicity or flow cytometry results. We describe the immunosuppression protocols and outcomes at 10 months of four renal transplant patients in whom anti-HLA DSAs were detected by Luminex® but not by CDC and flow cytometry. The four patients underwent induction treatment with five doses of thymoglobulin at 1.25 mg/kg and 5 doses of intravenous immunoglobulin (IVIG) at 400 mg/kg. In addition, one patient received 20 mg basiliximab on the day of transplant and on post-operative day 4; another patient underwent three sessions of plasmapheresis on days -5, -3, and -1 and also received 1200 mg eculizumab prior to transplant, 900 mg on day 1, and 600 mg each week during one month. In all of them, the maintenance immunosuppressive regimen consisted of tacrolimus, mycophenolate acid and deltisone. All patients had good short-term outcomes. Our findings suggest that patients with anti-HLA DSAs detected only by Luminex® should be monitored closely and can be treated successfully with induction therapy based on thymoglobulin and IVIG.

Challenges with sensitized recipients in pediatric heart transplantation

The sensitization of patients to human leukocyte antigens prior to heart transplantation is increasingly being recognized as an important challenge both before and after the transplant, and the effects of sensitization on clinical outcomes are just beginning to be understood. Many patients are listed with the requirement of a negative prospective or virtual crossmatch prior to accepting a donor organ. This strategy has been associated with both longer waitlist times and higher waitlist mortality. An alternative approach is to transplant across a potentially positive crossmatch while utilizing strategies to decrease the significance of the human leukocyte antigen antibodies. This review will examine the challenges and the impact of sensitization on pediatric patients prior to and following heart transplantation.