Incidência de reações adversas associadas ao uso de inibidores de calcineurina em pacientes submetidos ao transplante pulmonar / Incidence of adverse reactions associated with the use of calcineurin inhibitors in patients undergoing lung transplantation

Introdução: O uso de terapia imunossupressora é de extrema importância no transplante pulmonar, entretanto existem diversas reações adversas (RAMs) associadas ao seu uso. Neste trabalho buscamos descrever a incidência de perda de função renal (FR), diabetes mellitus (DM), hipertensão arterial sistêmica (HAS) e hipercolesterolemia associadas ao uso de ICN na população de transplantados pulmonares do Hospital de Clínicas de Porto Alegre após 1 ano de transplante.Metodologia: Estudo de coorte retrospectivo, conduzido no Hospital de Clínicas de Porto Alegre. Foram incluídos os pacientes transplantados de pulmão no período de 2016 a 2018.Resultados: Após um ano do transplante 56,5% (13/23) tiveram uma perda de FR em comparação ao basal, mas com valores ainda dentro da normalidade e 30,4% (7/23) perderam FR. A diferença de FR antes e após o transplante foi estatisticamente significativa com p < 0,001, no entanto não foi observado diferença entre os ICN (p = 0,499). Entre as variáveis: DM, HAS e Hipercolesterolemia, apenas o desenvolvimento de HAS foi estaticamente significativo quando comparado ao período pré-transplante (p < 0,001).Conclusão: Nossos dados demonstraram importante perda de FR após uso de imunossupressores ICN, corroborando com dados já publicados, no entanto, não foi possível identificar associação com ICN específico, sugerindo que benefícios na intercambialidade de terapias entre os ICN na tentativa de preservação da FR devem ser melhor estudados. Diante da possibilidade de desenvolvimento de RAMs associadas ao uso de imunossupressores, destacamos a importância da inserção do farmacêutico clínico nas equipes de transplante.

Introduction: Immunosuppressive therapy is extremely important in lung transplantation, but there are several adverse drug reactions (ADRs) associated with its use.Objective: To report the incidence of loss of renal function (RF), diabetes mellitus (DM), systemic arterial hypertension (SAH), and hypercholesterolemia associated with the use of calcineurin inhibitors (CNIs) in the population of lung transplant recipients at Hospital de Clínicas de Porto Alegre at 1 year after transplant. Methods: We conducted a retrospective cohort study of patients undergoing a lung transplant at Hospital de Clínicas de Porto Alegre from 2016 to 2018.Results: At 1 year after transplant, 56.5% (13/23) had loss of RF compared with baseline, but the values remained within the normal range, whereas 30.4% (7/23) had complete loss of RF. There was a statistically significant difference in RF before and after transplant (p < 0.001), but not in CNIs (p = 0.499). Among the variables DM, SAH, and hypercholesterolemia, only the development of SAH was statistically significant compared with the pre-transplant period (p < 0.001).Conclusion: Our data demonstrated an important loss of RF after the use of CNI immunosuppressants, which is consistent with published data. However, no association was identified with the type of CNI, suggesting that the benefits of the interchangeability of CNI therapies aimed at preserving RF should be further studied. Given the potential occurrence of ADRs associated with the use of immunosuppressants, we highlight the importance of the presence of a clinical pharmacist in the transplant team.

Histoplasmosis: informe de un caso / Histoplasmosis: a case report

Objetivo: Describir el diagnóstico y el tratamiento interdisciplinario de un caso clínico de histoplasmosis. Caso clínico: Un paciente masculino de 39 años, con antecedentes de consumo de drogas, alcohol, tabaquismo crónico y VIH+ sin adherencia al tratamiento, acudió al Servicio de Odontología por una interconsulta del Servicio de Clínica Médica para la evaluación de lesiones erosivas en paladar duro y blando, reborde alveolar anterior, dorso lingual y lesión tumoral en encía anterosuperior. El diagnóstico definitivo se obtuvo por medio del análisis de muestras de biopsia transbronquial, lavado broncoalveolar y biopsia de lesión en piel. El paciente recibió tratamiento sistémico con antimicóticos (anfotericina B e itraconazol según esquema) y tratamiento local con colutorio de clorhexidina al 0,12% y 100.000 UI de nistatina en suspensión. Al momento del alta, presentaba una considerable mejoría de su estado general y de las lesiones orales, con disminución de sintomatología dolorosa. Se indicó turno para control a los 7 días de forma ambulatoria, al cual el paciente no asistió. El abordaje interdisciplinario y el análisis de los diferentes aspectos socioeconómicos, culturales, ambientales y sistémicos del paciente facilitaron el diagnóstico temprano de la enfermedad (AU)

Aim: To describe the diagnosis and interdisciplinary treatment of a clinical case of histoplasmosis. Clinical case: 39-year-old male patient with a history of drug abuse, alcohol, and chronic smoking, HIV+ without treatment compliance, attends the dental department referred by the medical department for the diagnosis of erosive lesions in the hard and soft palate, anterior alveolar ridge, lingual dorsum and tumor lesion in the anterosuperior gingiva. The definitive diagnosis was obtained by the analysis of transbronchial biopsy, bronchoalveolar lavage and skin lesion biopsy. The patient received systemic treatment with antifungals (amphotericin b, itraconazole according to protocol), and local treatment with 0.12% chlorhexidine mouthwash and 100,000 IU nystatin suspension. At the time of medical discharge, the patient presented a considerable improvement in his general condition and of the oral lesions with a reduced pain. A 7 days recall was prescribed, however the patient failed to attend. The interdisciplinary approach to the patient and the analysis of the different socio-economic, cultural, environmental and systemic aspects of the patient facilitates the early diagnosis of the disease (AU)

Influencia del polimorfismo de CYP3A4 y CYP3A5 en la farmacocinética de tacrolimus en receptores de trasplante renal. Revisión narrativa / Influence of CYP3A4 and CYP3A5 polymorphism of the pharmacokinetics of tacrolimus in renal transplant recipients. Narrative review

El uso de inhibidores de calcineurina, en particular de tacrolimus como terapia inmunosupresora se ha generalizado a nivel mundial, permitiendo mejorar la tasa de sobrevida del injerto y la calidad de vida del paciente trasplantado. Con el acceso a los estudios de farmacogenética, los grupos de trasplante a nivel mundial se han visto motivados a realizar estudios genéticos que permitan interpretar la influencia de polimorfismos de genes como mTOR, PPP3CA, FK BP1A, FKBP2, y FOXP3, sin embargo, los más estudiados en la población trasplantada para optimizar la dosis de tacrolimus y ciclosporina son los polimorfismos del citocromo p450, CYP3A4 y CYP3A5.El objetivo de la presente revisión narrativa es examinar publicaciones recientes que estudien la relación entre el polimorfismo de CYP3A4/5 y el metabolismo de tacrolimus en pacientes trasplantados renales.Se revisó literatura reciente extraída de los sitios NCBI PubMed y PharmGKB.org en la que se hubiera investigado la influencia de los polimorfismos de CYP3A4/5 en el metabolismo de tacrolimus en trasplantados renales. Se identificó variaciones genéticas de CYP3A4/5 en pacientes trasplantados tratados con tacrolimus que permitirán a los médicos trasplantólogos dosificar de manera precisa el inmunosupresor. El uso de análisis farmacogenéticos permite determinar las variables genéticas del CYP3A4/5, y por lo tanto la toma de decisiones personalizadas en la dosis de inicio y de mantenimiento del inmunosupresor tacrolimus para alcanzar los niveles óptimos y con ello disminuir el riesgo de rechazo, de infecciones asociadas a inmunosupresión, y de toxicidad por el medicamento.

The use of the calcineurin inhibitor tacrolimus as immunosuppressive therapy, has become widespread world-wide, improving the graft's survival rate and the quality of life of the transplanted patient. With access to pharmacogenetic studies, transplant groups worldwide have been motivated to conduct genetic studies to inter-pret the influence of polymorphisms of genes such asmTOR, PPP3CA, FK BP1A, FKBP2, and FOXP3, however the most studied in the transplanted population to optimize the dose of tacrolimus and cyclosporine are those of cytochrome p450,CYP3A4 and CYP3A5. The objective of this narrative review is to examine recent publications studying the relationship betweenCYP3A4/5polymorphism, and tacrolimus metabolism in renal transplant patients. Literature extracted from the NCBI PubMed site and PharmGKB.org, from the past five years, which investigated the influence ofCYP3A4/5polymorphism on tacrolimus metabolism in renal transplants had been reviewed. Genetic variations ofCYP3A4/5 were identified in transplant patients treated with tacrolimus that will allow transplant physicians to dose the immunosuppressant accurately. The use of pharmacogenetic analyses makes it possible to determine the genetic polymorphisms ofCYP3A4/5, and therefore the decision-making cus-tomized at the starting and maintenance dose of the tacrolimus immunosuppressant to achieve optimal levels and thereby reduce the risk of rejection, immunosuppression-associated infections, and drug toxicity.

Esporotricose pulmonar em paciente imunocompetente: relato de caso / Pulmonary sporotrichosis in immunocompetent patient: case report

A forma extracutânea pulmonar da esporotricose, uma infecção causada por espécies geneticamente distintas de um fungo dimórfico do gênero Sporothrix, é rara, com poucos casos relatados na literatura. Trata-se de um caso de uma mulher de 55 anos, residente da região do Barreiro de Belo Horizonte/Minas Gerais, que buscou o serviço de infectologia de um hospital público de Belo Horizonte com história de emagrecimento, dispneia aos pequenos esforços, tosse crônica e calafrios vespertinos de três anos de evolução. Foi tratada para pneumonia bacteriana, em cinco ocasiões, sem melhora clínica. Apresentou tomografia computadorizada de tórax com cavitação residual e lesões escavadas pulmonares. A paciente foi internada com quadro de dispneia aos pequenos esforços, tosse e expectoração purulenta, sendo sua cultura de escarro positiva para Sporothrix spp. Foi instituído o tratamento padrão ouro para esporotricose pulmonar, inicialmente, com itraconazol, 200 mg, duas vezes ao dia, entretanto, após 10 meses, a melhora clínica e radiológica não foi satisfatória e optou-se pela internação a administração de anfotericina B complexo lipídico endovenosa 4 mg/kg/dia. Em menos de 1 mês a paciente apresentou piora do quadro e evoluiu a óbito, apesar de ter recebido 2g de dose acumulada de anfotericina

The pulmonary extracutaneous form of sporotrichosis, an infection caused by genetically distinct species of a dimorphic fungus of the genus Sporothrix, is rare, with few cases reported in the literature. This is a case of a 55-year-old woman, resident of the Barreiro region in Belo Horizonte/ Minas Gerais, who sought the infectious disease service of a public hospital in Belo Horizonte with a history of weight loss, dyspnea at small efforts, chronic cough and three-year-old vespertinus chills. She was treated for bacterial pneumonia on five occasions without clinical improvement. He presented computed tomography of the chest with residual cavitation and excavated pulmonary lesions. The patient was hospitalized with dyspnea on small efforts, cough and purulent sputum, and her sputum culture was positive for Sporothrix spp. The gold standard treatment for pulmonary sporotrichosis was instituted, initially with itraconazole, 200 mg twice a day, however, after 10 months, the clinical and radiological improvement was not satisfactory and the administration of intravenous amphotericin B lipid complex 4 mg/kg/day was chosen. In less than 1 month the patient presented worsening of the condition and died, despite receiving 2g of accumulated dose of amphotericin B lipid complex.

Mulheres submetidas ao transplante de medula óssea: impacto dos quimioterápicos e da doença do enxerto contra o hospedeiro sobre o sistema reprodutor / Women undergoing bone marrow transplantation: impact of chemotherapy and graft-versus-host disease (GVHD) on the feminine reproductive system

O transplante de medula óssea (TMO) é um procedimento indicado para o tratamento de doenças hematológicas, que afetam muitas mulheres jovens. O aperfeiçoamento dos cuidados durante o TMO proporciona altos índices de cura e de sobrevida. No entanto, pode deixar sequelas em vários órgãos e sistemas, entre eles o sistema reprodutor e os órgãos genitais, impactando negativamente a qualidade de vida das receptoras do TMO. O objetivo desta publicação foi realizar uma revisão narrativa sobre o tema e propor um protocolo assistencial que torne acessível os cuidados relacionados à saúde sexual e reprodutiva a esse grupo especial de mulheres, baseado em dados clínicos de um ambulatório de assistência ginecológica às mulheres transplantadas no Hospital Amaral Carvalho, em Jaú, no interior de São Paulo.(AU)

Bone marrow transplantation (BMT) is indicated for the treatment of hematological diseases which affect many young women. The improvement of care during BMT procedures provides higher cure and survival rates. however, it can cause sequelae in various organs and systems, including the reproductive system and genitals, negatively impacting quality of life. The purpose of this publication is to present a narrative review related to this theme and to propose a healthcare protocol that allows sexual and reproductive care in this special group of patients, based on the clinical experience of a gynecological outpatient clinic at the Amaral Carvalho Hospital, in Jaú (SP) which specifically care for these women.(AU)

Heart Transplantation for Chagas Cardiomyopathy

Abstract Heart transplantation (HT) is an established treatment for patients with advanced heart failure (HF). Chagas disease (CD), caused by the Trypanosoma cruzi (T.cruzi) is an important cause of HF in Latin America. Considering CD is a chronic infectious disease, the use of immunosuppressive therapy after HT can reactivate T. cruzi infection and compromise outcomes. Early diagnosis and treatment of this complication is extremely important, which requires knowledge, experience, and a high degree of suspicion by transplant physicians. Furthermore, with the international immigration of people, CD is no longer exclusive to Latin America, since a large number of immigrants with T. cruzi infection are living in non-endemic countries. This phenomenon represents not only a new global epidemiological problem, but also a challenge for transplant teams. This review aims to discuss the peculiarities of HT in the context of CD, with a focus on reactivation of the infection, clinical manifestations, etiological treatment of T. cruzi and differential diagnosis with allograft rejection, among HT recipients.

Infección por citomegalovirus en pacientes reumatológicos: análisis de un caso y revisión de la literatura / Cytomegalovirus infection in rheumatologic patients: a case report and literature review

El Citomegalovirus es un microorganismo capaz de generar infecciones severas en pacientes inmunosuprimidos. Existe abundante información respecto a la infección en pacientes inmunosuprimidos por VIH o en relación a trasplante de órganos sólidos o hematopoyéticos. No ocurre lo mismo con los pacientes portadores de enfermedades autoinmunes. Si bien la clínica puede ser inespecífica y dificultar la sospecha diagnóstica, la clave está en determinar al paciente de riesgo para la infección y así realizar un diagnóstico precoz. Se presenta el caso de una mujer de 56 años, portadora de una polimiositis de difícil tratamiento, que en un contexto de terapia en base a corticoides e inmunosupresores (azatioprina y metotrexato), desarrolla cuadro febril asociado a fatiga, cuyo estudio concluyó una infección por Citomegalovirus, tratado exitosamente con Valganciclovir.

Cytomegalovirus is a microorganism associated with severe infections in immunosuppressed patients. There is abundant information regarding infection in HIV immunosuppressed patients or in relation to solid or hematopoietic organ transplantation. The same does not happen with patients with rheumatic diseases. Although the clinic can be nonspecific and hinder diagnostic suspicion, the key is to determine the patient at risk for the infection and thus make an early diagnosis. We present a case of a 56-year-old woman with a difficult-to-treat polymyositis, who, in a context of corticosteroid and immunosuppressive agents (azathioprine and methotrexate), develops a fever associated with fatigue, whose study con-cluded an infection due to Cytomegalovirus, successfully treated with Valganci-clovir.

BK virus salivary shedding and viremia in renal transplant recipients

Abstract Objectives: This study aimed to verify the presence of polyomavirus BK (BKPyV) in the saliva of kidney transplant recipients and to correlate it with blood viremia. Material and Methods: We have conducted a cross-sectional study with a sample involving 126 renal transplant recipients. 126 samples of saliva and 52 samples of blood were collected from these patients. Detection and quantification of BKPyV were performed using a real-time PCR. To compare the presence of BKPyV in blood and saliva, the binomial proportion test was used. To verify associations between salivary shedding BKPyV and post-transplant periods (in months), the Mann-Whitney test was used. Spearman's correlation was used to correlate the viral load in the saliva with blood of kidney transplant recipients. Results: The mean age of the study group was 51.11±12.45 years old, and 69 participants (54.8%) were female, with a mean post-transplantation time of 4.80±6.04 months. BKPyV was quantified in several samples of saliva and blood, with medians of 1,108 cp/mL and 1,255 cp/mL, respectively. Only 16/52 (30.8%) participants presented BKPyV in blood, and 59/126 (46.8%) excreted the virus in saliva (p=0.004). BKPyV shedding was found in patients at a shorter post-transplantation period (3.86±5.25, p=0.100). A weak correlation was observed between viral quantification in saliva and blood (Spearman's correlation coefficient=0.193). Conclusion: The results of this study suggested that, although saliva excretes more BKPyV than blood, there is no reliable correlation between salivary shedding and blood viremia, showing two independent compartments of viral replication.

Sarcoma de Kaposi intestinal en paciente trasplantado renal / Intestinal KaposiÆs Sarcoma in renal transplant patient

El sarcoma de Kaposi (SK) es una neoplasia vascular, en la cual podemos distinguir cuatro formas clínicas: la clásica o mediterránea, endémica o africana, asociada al VIH y la iatrogénica. Sus manifestaciones clínicas más frecuentes son las lesiones mucocutáneas y afectación de ganglios linfáticos si bien puede cursar con afectación a nivel visceral. Presentamos a continuación el caso de un paciente trasplantado renal que fue diagnosticado de un sarcoma de Kaposi intestinal, sin lesiones cutáneas asociadas

Kaposi's sarcoma (KS) is a vascular neoplasm, in which we can distinguish four clinical forms: the classic or Mediterranean, endemic or African, associated with HIV and iatrogenic. Its most frequent clinical manifestations are mucocutaneous lesions and lymph node involvement, although it may manifest with involvement at the visceral level. We present the case of a renal transplant patient who was diagnosed with an intestinal Kaposi's sarcoma, with no associated cutaneous lesions

Skin disorders in renal transplant recipients: a retrospective study

Abstract: Background: Immunosuppressive therapy, which is necessary to avoid graft rejection in renal transplant recipients, presents an increased risk of several pathologies, namely infectious and neoplastic. Objectives: To identify the most frequent skin diseases and their clinical and demographical risk factors within a population of renal transplant recipients. Methods: A retrospective study of renal transplant recipients referred to dermatology visit and observed for the first time from January 2008 to December 2014. Results: The study included 197 patients, 120 men (60,9%). Mean age was 50,7 years (±13,4). 12 patients (6,1%) had previous skin cancer. Infections were the most frequent reason of referral (93/197; 44%). From the total referred, 18,3% (36/197) presented pre-cancerous lesions. Malignancy was diagnosed in 36 patients (18,3%), with 29 non-melanoma skin cancers (14,7%) and 7 Kaposi sarcomas (3,6%). Ratio of basal cell carcinoma to squamous cell carcinoma was 1,1:1. Non-melanoma skin cancer was significantly associated with older age (p = 0,002), male gender (p = 0,028), history of previous skin cancer (p = 0,002) and higher duration of immunosuppressive therapy (p<0,001). Study limitations: Retrospective study, with data from the first visit in dermatology. We didn't made classification on skin-types. Conclusions: The great incidence of cutaneous infections and skin cancer is responsible for a significant morbidity. It is important to assure the regular dermatological follow-up of renal transplant recipients, which will promote the prevention, an early diagnosis and an efficient treatment.

Study of factors affecting the incidence of skin cancer in patients after liver transplant

Abstract: Background: Many factors are currently being identified as potential inductors of skin cancer in patients after a liver transplant, among them, immunosuppressive regimen. Objective: To study the factors that influence the incidence of skin cancer in patients after liver transplant. Methods: We have carried out a retrospective and observational study with 170 transplanted patients who had undergone transplantation from 1997 to 2010. We have adjusted the multiple logistic regression model (saturated model) to the ensemble of collected data using skin cancer as dependent variable, indicated in anatomopathological analysis between 1997 and 2014. Results: Incidence of skin cancer was 9.4%. Predictors were incidence of diabetes in the third year after the transplantation (p=0.047), not using tacrolimus in the first year after the transplantation (p=0.025) and actinic keratosis (p=0.003). Study Limitations: An important limitation is that the interpretation of the results was based on information collected of patients undergoing transplantation at a single center. Future research, multicentric and involving larger and more diverse populations, are needed. Conclusions: Factors found might contribute to Brazilian surveillance programs associated with decreased incidence of skin cancer.

Neoplasias extra-colónicas en pacientes con enfermedad inflamatoria intestinal / Extra-intestinal malignancies in patients with inflammatory bowel disease

Patients with inflammatory bowel disease (IBD) have shown to be at increased risk of developing extraintestinal malignancies. Immunomodulators (immunosuppressant and anti-tumor necrosis factor) diminish the mucosal inflammatory response changing the evolution of the disease, especially when these strategies are introduced earlier. However, therapies that alter the immune system may also promote carcinogenesis. Treatment of IBD in patients with prior malignancy is challenging and the final decision regarding therapeutic strategy should be made on a case-by-case basis. The purpose of this review is to show the characteristics of extra-colonic cancer in patients with IBD, including risks, pathogenesis and management of IBD after cancer diagnosis, the effect of neoplasm treatment on IBD, and the effect of IBD and its treatments on cancer outcomes.

Los pacientes con enfermedad inflamatoria intestinal (EII) presentan un mayor riesgo de desarrollar neoplasias extraintestinales. Los inmunomoduladores (inmunosupresores y terapia biológica anti-TNF) disminuyen la respuesta inflamatoria a nivel de la mucosa, modificando la evolución de la enfermedad, especialmente cuando son introducidos precozmente. Sin embargo, estas terapias pueden alterar el sistema inmune y promover la carcinogénesis. El tratamiento de la EII en pacientes con antecedentes de cáncer es un desafío y la decisión final sobre la estrategia terapéutica debe ser determinada caso a caso. Esta revisión tiene como objetivo mostrar las características de las neoplasias extra-intestinales en pacientes con EII, incluyendo los riesgos, patogénesis y manejo de la EII posterior al diagnóstico del cáncer, el efecto de la neoplasia sobre el tratamiento de la EII y el efecto de la EII y su tratamiento sobre el cáncer.

The need for endodontic treatment and systemic characteristics of hematopoietic stem cell transplantation patients

Abstract The aim of this study is to investigate the relationship between the epidemiological and clinical profiles of patients before and after hematopoietic stem cell transplantation (HSCT) and the need for endodontic treatment. The subjects included 188 individuals enrolled in the dental care program for transplanted patients of the School of Dentistry, Federal University of Minas Gerais (Faculdade de Odontologia da Universidade Federal de Minas Gerais, FO-UFMG) from March 2011 through March 2016. The patients were subjected to an HSCT conditioning dental regimen based on a thorough clinical and radiographic evaluation. Intraoral periapical and bite-wing X-rays were obtained, and after evaluation, specific dental treatment was planned and performed. The following demographic and clinical data were collected from the patients' medical records: age, gender, transplantation stage, primary disease, transplant type, medication used, complete blood count at the time of visit, and need for endodontic treatment. The Kolmogorov-Smirnov and the chi-square tests were used. Leukemia (31.3%) and multiple myeloma (17.9%) were the most prevalent primary diseases. Most patients were subjected to allogeneic-related transplantation (83.6%). Most patients exhibited platelet counts and hemoglobin concentrations below the reference values in the pre-transplantation stage, while the neutrophil and platelet counts and the hemoglobin levels were within the reference ranges in the post-transplantation stage. The proportions of individuals requiring endodontic treatment were similar between the pre- and post-transplantation groups: 24.3% and 24.7%, respectively. The systemic conditions of the patients referred for dental treatment were compromised.

Heart transplantation: review / Transplante cardíaco: revisão

ABSTRACT Heart transplantation is currently the definitive gold standard surgical approach in the treatment of refractory heart failure. However, the shortage of donors limits the achievement of a greater number of heart transplants, in which the use of mechanical circulatory support devices is increasing. With well-established indications and contraindications, as well as diagnosis and treatment of rejection through defined protocols of immunosuppression, the outcomes of heart transplantation are very favorable. Among early complications that can impact survival are primary graft failure, right ventricular dysfunction, rejection, and infections, whereas late complications include cardiac allograft vasculopathy and neoplasms. Despite the difficulties for heart transplantation, in particular, the shortage of donors and high mortality while on the waiting list, in Brazil, there is a great potential for both increasing effective donors and using circulatory assist devices, which can positively impact the number and outcomes of heart transplants.

RESUMO O transplante cardíaco é atualmente a abordagem cirúrgica definitiva padrão-ouro no tratamento da insuficiência cardíaca refratária. No entanto, a escassez de doadores limita a realização de um número maior de transplantes cardíacos, situação em que vem aumentando a utilização de dispositivos de assistência circulatória mecânica. Com indicações e contraindicações bem estabelecidas, além de diagnóstico e tratamento de rejeição, por meio de protocolos definidos de imunossupressão, os resultados do transplante cardíaco são muito favoráveis. Dentre as complicações precoces que podem impactar a sobrevida, destacamos a disfunção primária do enxerto, a disfunção do ventrículo direito, rejeição e infecções; já as complicações tardias incluem a doença vascular do enxerto e as neoplasias. Apesar das dificuldades para realização do transplante cardíaco, em especial pela escassez de doadores e pela elevada mortalidade em fila de espera, no Brasil, existe um grande potencial, tanto no aumento de doadores efetivos, quanto na utilização de dispositivos de assistência circulatória, o que pode vir a impactar positivamente no número e nos resultados do transplante cardíaco.

Manifestaciones cutáneas en adultos con trasplante hepático del Hospital Clínico de la Universidad de Chile / Skin manifestations in adults with a liver allograft

Background: Skin manifestations after liver transplantation are increasing due to long term immunosuppressive therapy along with an increase in patient survival. Several studies have reported dermatologic complications following renal transplant, but few have studied dermatologic problems after liver transplantation. Aims: To describe the different types of cutaneous lesions encountered in adults receiving a liver allograft. To evaluate the frequency of cutaneous manifestations of patients in the liver transplant waiting list. Material and Methods: Eighty patients submitted to a liver transplant and 70 patients in the liver transplant waiting list were evaluated with a complete dermatological physical examination. Results: Sixty one percent of patients with a liver allograft had at least one skin manifestation. Of these, 34% had superficial fungal infections, 31% had viral infections, 20% had cutaneous side effects due to immunosuppressive treatment, 10% had malignant lesions, 2% had bacterial infections and one patient had a graft versus host disease. Only 28% of patients in the liver transplant waiting list had dermatologic problems, and the vast majority were lesions linked to liver cirrhosis. Conclusions: Cutaneous infections were the most common skin problems in liver transplant patients. Although neoplastic lesions are the most commonly mentioned lesions in the literature, only a 10% of our liver transplant patients presented these type of lesions.

Oral changes in individuals undergoing hematopoietic stem cell transplantation / Alterações orais em indivíduos submetidos à transplante de células hematopoiéticas

INTRODUCTION: Patients undergoing hematopoietic stem cell transplantation receive high doses of chemotherapy and radiotherapy, which cause severe immunosuppression. OBJECTIVE: To report an oral disease management protocol before and after hematopoietic stem cell transplantation. METHODS: A prospective study was carried out with 65 patients aged > 18 years, with hematological diseases, who were allocated into two groups: A (allogeneic transplant, 34 patients); B (autologous transplant, 31 patients). A total of three dental status assessments were performed: in the pre-transplantation period (moment 1), one week after stem cell infusion (moment 2), and 100 days after transplantation (moment 3). In each moment, oral changes were assigned scores and classified as mild, moderate, and severe risks. RESULTS: The most frequent pathological conditions were gingivitis, pericoronitis in the third molar region, and ulcers at the third moment assessments. However, at moments 2 and 3, the most common disease was mucositis associated with toxicity from the drugs used in the immunosuppression. CONCLUSION: Mucositis accounted for the increased score and potential risk of clinical complications. Gingivitis, ulcers, and pericoronitis were other changes identified as potential risk factors for clinical complications. .

INTRODUÇÃO: Pacientes submetidos a transplante de células hematopoiéticas recebem altas doses de quimioterapia e radioterapia que podem causar imunossupressão e doenças orais graves. OBJETIVO: Apresentar um protocolo de avaliação de doenças orais antes e após transplante de células hematopoiéticas. MÉTODO: Estudo clínico prospectivo de 65 pacientes com idade acima de 18 anos, com doenças hematológicas submetidas a transplante de células hematopoiéticas, divididos em dois grupos: A (transplante alogênico, 34 pacientes) e B (transplante autólogo). Foram realizadas três avaliações odontológicas: período antes do transplante (momento 1), uma semana (momento 2) e 100 dias após o transplante (momento 3). Em cada momento as alterações orais foram pontuadas e classificadas como leve, moderada e grave. RESULTADOS: As alterações orais mais frequentes foram: gengivite, pericoronite do terceiro molar e úlceras. Entretanto nos momentos dois e três a principal doença foi a mucosite associada a toxicidades das drogas usadas na imunossupressão. CONCLUSÃO: Mucosite foi principal alteração, com a pontuação mais alta e com maior risco de complicações. Gengivites, úlceras e pericoronites foram outras alterações com risco menor de complicações. .

Effects of immunosuppression with tacrolimus and mycophenolate mofetil on renal histology and function in single kidney rats submitted to ischemia and reperfusion

PURPOSE: To evaluate renal histological changes and renal function in single kidney rats submitted to renal ischemia-reperfusion and to immunosuppression with tacrolimus and mycophenolate-mofetil. METHODS: Experimental study with 80 Wistar rats distributed into control, Sham and six other groups treated with immunosuppressive drugs. Animals undergoing surgery, right nephrectomy and left renal clamping, killed on the 14th day and analyzed for renal histology, urea and creatinine. RESULTS: The group receiving tacrolimus at higher doses (T3) showed renal histological lesions indicative of early nephrotoxicity, and significant increase in urea and creatinine. The group M (mycophenolate-mofetil alone) and the group M2 (mycophenolate-mofetil combined with half the usual dose of tacrolimus) presented a slight rise in serum urea. The groups using mycophenolate-mofetil alone or combined with tacrolimus showed creatinine levels similar to that of the group T3. CONCLUSIONS: Histologically, the association of injury by ischemia-reperfusion with the use of tacrolimus or mycophenolate-mofetil alone demonstrated a higher rate of renal changes typical of early nephrotoxicity. In laboratory, the combination of injury by ischemia-reperfusion with tacrolimus at higher doses proved to be nephrotoxic. .

An analysis of tacrolimus-related complications in the first 30 days after liver transplantation

OBJECTIVES: Orthotopic liver transplantation has improved survival in patients with end-stage liver disease; however, therapeutic strategies that achieve ideal immunosuppression and avoid early complications are lacking. To correlate the dose and level of Tacrolimus with early complications, e.g., rejection, infection and renal impairment, after liver transplantation. From November 2011 to May 2013, 44 adult liver transplant recipients were studied in this retrospective comparative study. RESULTS: The most frequent indication for liver transplantation was hepatitis C cirrhosis (47.7%), with a higher prevalence observed in male patients (68.18%). The ages of the subjects ranged from 19-71 and the median age was 55.5 years. The mean length of the hospital stay was 16.1±9.32 days and the mean Model for End-stage Liver Disease score was 26.18±4.28. There were five cases of acute cellular rejection (11.37%) and 16 cases of infection (36.37%). The blood samples that were collected and analyzed over time showed a significant correlation between the Tacrolimus blood level and the deterioration of glomerular filtration rate and serum creatinine (p<0.05). Patients with infections had a higher serum level of Tacrolimus (p = 0.012). The dose and presence of rejection were significantly different (p = 0.048) and the mean glomerular filtration rate was impaired in patients who underwent rejection compared with patients who did not undergo rejection (p = 0.0084). CONCLUSION: Blood Tacrolimus levels greater than 10 ng/ml were correlated with impaired renal function. Doses greater than 0.15 mg/kg/day were associated with the prevention of acute cellular rejection but predisposed patients to infectious disease. .

Epidemiological profile of nonmelanoma skin cancer in renal transplant recipients: experience of a referral center

BACKGROUND: Nonmelanoma skin cancer is the most common form of cancer in humans and also the malignant disease that is increasingly common among kidney transplant recipients. OBJECTIVE: To determine the epidemiological characteristics of renal transplant recipients with nonmelanoma skin cancer seen at a referral transplantation center. METHODS: Cross-sectional descriptive study with renal transplant recipients presenting nonmelanoma skin cancer, treated at a transplantation referral center between 08/01/2004 and 08/31/2009. Analyzed variables were: gender, age, skin phototype, occupational and recreational sun exposure, use of photoprotection, personal and family history of non-melanoma skin cancer, clinical type and location, time between transplantation and the appearance of the first nonmelanoma skin cancer, occurrence of viral warts, timing of transplantation, type of donor, cause of kidney failure, previous transplants, comorbidities, pre-transplant dialysis, type and duration of dialysis. RESULTS: 64 subjects were included. Males - 71.9%; low skin phototypes (up to Fitzpatrick III) - 89%; mean age - 57.0 years - and mean age at transplant - 47.3 years; sun exposure - 67.2% occupational - and 64.1% recreational; photoprotection - 78.2% (although only 34.4% in a regular manner); squamous cell carcinoma - 67.2%; squamous cell carcinoma/basal cell carcinoma ratio - 2:1; personal history of nonmelanoma skin cancer - 25% - and family history - 10.9%; location at photoexposed area - 98.4%; average latency time between transplantation and first nonmelanoma skin cancer appearance - 78.3 months; viral warts (HPV) after transplant - 53.1%; average timing of transplantation - 115.5 months; living donor - 64.1%; triple regimen (antirejection) - 73.2%; comorbidities - 92.2%; pre-transplant dialysis - 98.4%; hemodialysis - 71.7%; average duration of dialysis - 39.1 months; previous transplants - 3.1%; hypertension as cause of renal failure ...