Múltiples reacciones adversas graves a fármacos en un paciente luego de la infección por COVID-19: informe de un caso / Drug-induced severe cutaneous adverse reactions in a patient after COVID-19 infection: case report

Durante la pandemia por COVID-19 se observaron diversas reacciones adversas a fármacos. Esto pudo haber estado relacionado con una mayor susceptibilidad inmunológica de los pacientes con SARS-CoV-2 a presentar este tipo de cuadros, así como también con la exposición a múltiples medicamentos utilizados en su tratamiento. Comunicamos el caso de un paciente con una infección respiratoria grave por COVID-19, que presentó 2 reacciones adversas graves a fármacos en un período corto de tiempo. (AU)

During the COVID-19 pandemic, various adverse drug reactions were observed. This could have been related to a greater immunological susceptibility of patients with SARS-CoV-2 to present this type of symptoms, as well as exposure to multiple drugs used in their treatment. We report the case of a patient with a severe respiratory infection due to COVID-19, who presented 2 serious adverse drug reactions associated with paracetamol in a short period of time. (AU)

Abordaje Terapéutico de Agrandamiento Gingival Influenciado por Ciclosporina y Nifedipino. Reporte de Caso / Therapeutic Approach of Gingival Enlargement Influenced by Cyclosporine and Nifedipine. Case Report

RESUMEN: Este reporte de caso muestra un paciente atendido en el Postítulo de Periodoncia de la Facultad de Odontología de la Universidad de Chile con diagnóstico de Agrandamiento Gingival influenciado por ciclosporina y nifedipino. El abordaje terapéutico consideró la fase sistémica, la fase higiénica con el tratamiento periodontal no quirúrgico para lograr la eliminación de la infección periodontal antes y después de la fase quirúrgica, y la fase de terapia de soporte periodontal. Se logró así la eliminación de los agrandamientos gingivales influenciados por ciclosporina y nifedipino.

ABSTRACT: This case report shows a patient attended in the Postgraduate Periodontics Program at the Faculty of Dentistry of the University of Chile with a diagnosis of Gingival Enlargement influenced by cyclosporine and nifedipine. The therapeutic approach considered the systemic phase, the hygienic phase with the non-surgical periodontal treatment to achieve the elimination of the periodontal infection before and after the surgical phase, and the phase of periodontal support therapy. Thus, the elimination of gingival enlargements influenced by cyclosporine and nifedipine was achieved.

Agrandamiento gingival medicamentoso en paciente con trasplante renal tratado con ciclosporina A / Drug-induced gingival enlargement in a kidney transplant patient treated with cyclosporine A

Resumen El agrandamiento gingival medicamentoso se describe como un aumento de volumen anormal, exagerado y deformante de las encías, provocado por la ingesta de algunos medicamentos. Entre los más comunes se encuentran: fármacos anticonvulsivantes, antihipertensivos, particularmente los antagonistas del calcio e inmunosupresores. Se presentó el caso de un paciente del sexo masculino, de 44 años de edad, con antecedentes de hipertensión arterial e insuficiencia renal crónica, durante 10 y tres años respectivamente. Después de 22 meses de haber recibido un trasplante renal y tratamiento con ciclosporina, acude a consulta por aumento del volumen de las encías en ambos maxilares, clínicamente compatible con agrandamiento gingival medicamentoso generalizado y grave.

ABSTRACT Drug-induced gingival enlargement is described as an abnormal, exaggerated, and deforming growth of the gingiva caused by the ingestion of some medications. Anticonvulsants, antihypertensive calcium channel blockers and immunosuppressants are among the most common drugs. We present a 44-year-old male patient with a history of arterial hypertension and chronic renal failure, for 10 and three years, respectively. Twenty-two months after receiving a kidney transplant and treatment with cyclosporine, he visited the clinic due to an increase in the volume of the gums in both jaws, clinically compatible with a generalized and severe gingival enlargement.

Moderate to severe plaque psoriasis - treatment with drugs of the classic scheme

The Guidelines Project, an initiative of the Brazilian Medical Association, aims to combine information from the medical field in order to standardize producers to assist the reasoning and decision-making of doctors. The information provided through this project must be assessed and criticized by the physician responsible for the conduct that will be adopted, depending on the conditions and the clinical status of each patient.

Agrandamiento gingival medicamentoso en paciente con trasplante renal tratado con ciclosporina A / Drug-induced gingival enlargement in a kidney transplant patient treated with cyclosporine A

El agrandamiento gingival medicamentoso se describe como un aumento de volumen anormal, exagerado y deformante de las encías, provocado por la ingesta de algunos medicamentos. Entre los más comunes se encuentran: fármacos anticonvulsivantes, antihipertensivos, particularmente los antagonistas del calcio e inmunosupresores. Se presentó el caso de un paciente del sexo masculino, de 44 años de edad, con antecedentes de hipertensión arterial e insuficiencia renal crónica, durante 10 y tres años respectivamente. Después de 22 meses de haber recibido un trasplante renal y tratamiento con ciclosporina, acude a consulta por aumento del volumen de las encías en ambos maxilares, clínicamente compatible con agrandamiento gingival medicamentoso generalizado y grave.

Urticária crônica espontânea refratária aos anti-histamínicos: opção por ciclosporina / Antihistamine-refractory chronic spontaneous urticaria: opting for cyclosporine

Introdução: Anti-histamínico de segunda geração (AH1 2ªG) é o tratamento de escolha para pacientes com urticária crônica espontânea (UCE). Porém, cerca de 50% dos pacientes não responde a este tratamento. A ciclosporina é uma opção para os quadros mais graves. A ciclosporina tem propriedades imunossupressoras potentes, mas, apesar de sua eficácia, seu uso é limitado devido a diversos efeitos colaterais importantes. Objetivo: O objetivo deste estudo foi avaliar a resposta à ciclosporina em pacientes com UCE refratária aos anti-histamínicos. Método: Estudo retrospectivo baseado no prontuário eletrônico de pacientes com UCE refratária aos AH1 2ªG e que não responderam à introdução de outros medicamentos para controle da urticária. A ciclosporina foi indicada para todos os pacientes. A dosagem de D-dímero foi realizada em alguns pacientes. Resultados: Trinta pacientes participaram do estudo. Desses pacientes, 80% eram do sexo feminino, e a média de idade era de 42,8 anos. Previamente à introdução da ciclosporina, todos estavam em uso de AH1, 60% de AH2, 67% de montelucaste, 33,3% de hidroxicloroquina, e 56,7% de corticoide oral. A mediana de tempo de uso da ciclosporina foi de 11,5 meses. Em relação à eficácia, 40% dos pacientes apresentaram melhora dos sintomas, 40% não responderam ao tratamento, e em 20% dos pacientes a resposta não foi avaliada por suspensão da ciclosporina devido a efeitos colaterais, ou não foi introduzida devido a alterações clínicas ou laboratoriais prévias. Houve aumento dos níveis pressóricos em 9 pacientes (30%), e nefrotoxicidade em 5 pacientes (16,7%). Conclusões: Embora a ciclosporina seja uma boa opção terapêutica para pacientes com UCE refratária aos AH1, os efeitos colaterais são frequentes e devem ser monitorados.

Introduction: Second-generation antihistamines (sgAH1) are the treatment of choice for patients with chronic spontaneous urticaria (CSU). However, about 50% of the patients do not respond to this treatment. Cyclosporine is an option for more severe presentations. This drug has potent immunosuppressive properties. Despite its effectiveness, use is limited due to several serious side effects. Objective: The aim of this study was to assess response to cyclosporine in patients with antihistamine-refractory CSU. Method: This retrospective study was based on the electronic records of patients with sgAH1-refractory CSU who did not respond to the introduction of other drugs to control urticaria. Cyclosporine was indicated for all patients. D-dimer dosage was performed in some patients. Results: Thirty patients participated in the study. Of these, 80% were female and the mean age was 42.8 years. Prior to the introduction of cyclosporine, all patients were using AH1, 60% AH2, 67% montelukast, 33.3% hydroxychloroquine, and 56.7% oral corticosteroids. Median time of cyclosporine use was 11.5 months. Regarding efficacy, 40% of the patients showed improvement of symptoms, 40% did not respond to treatment, and in 20% response was not evaluated because the medication was withdrawn due to side effects or was not introduced based on previous clinical or laboratory abnormalities. There was an increase in blood pressure levels in 9 patients (30%) and nephrotoxicity in 5 (16.7%). Conclusions: Even though cyclosporine is a good therapeutic option for patients with AH1-refractory CSU, side effects are frequent and should be monitored.

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.

Agrandamiento gingival por ciclosporina: reporte de un caso / Gingival enlargement due to cyclosporine: a case report

El agrandamiento gingival (AG) es el aumento de volumen anormal de la encía que genera cambios estéticos y síntomas clínicos como sangrado gingival espontáneo o inducido, trastornos periodontales y migración patológica dentaria, entre otros. Este proceso patológico puede ser un efecto secundario a ciertos fármacos como anticonvulsivantes, bloqueadores de canales de calcio e inmunosupresores. Se presenta el caso de un paciente sexo masculino de 74 años de edad con antecedentes de trasplante renal, en tratamiento con ciclosporina, que acude por aumento del volumen intraoral, clínicamente compatible con agrandamiento gingival. Se realiza tratamiento basado en exodoncias, biopsia y control de placa. A los 2 meses se pudo observar una regresión de la lesión, y se confirma el diagnóstico con el estudio histopatológico. El manejo actual del tratamiento de esta enfermedad se basa en el control de la placa. Se sugiere dar un enfoque multidisciplinario y crear protocolos para derivar oportunamente antes de la expresión más agresiva de la enfermedad.

Gingival enlargement is an abnormal increased volume of the gum that induces cosmetic changes and clinical symptoms, such as gingival bleeding, periodontal disorders, pathological tooth migration, among others. This condition can be a side effect of certain drugs such as anticonvulsants, calcium channel blockers, and immunosuppressants. A 74 year-old male patient with a medical record of kidney transplant secondary to chronic renal failure receiving cyclosporine for the past 14 years is referred to our Hospital with the chief complaint of gingival enlargement. The treatment is based on tooth extractions, biopsy and periodontal treatment. A complete regression of the lesion was observed after two months. The current approach to treat this disease is focused on plaque control. A multidisciplinary approach should be used and clinical protocols prepared that allow early treatment and avoidance of more aggressive disease expression.

Eficacia y seguridad de eltrombopag en pacientes con aplasia medular severa, no tributarios a terapia triple inmunosupresora ni trasplante de medula ósea / Efficacy and safety of eltrombopag in patients with severe medullary aplasia, non-tributary to immunosuppressive triple therapy and bone marrow transplantation

INTRODUCCIÓN: Antecedentes: El presente dictamen responde a la solicitud de evaluación de tecnología sanitaria del uso fuera del petitorio de Eltrombopag en pacientes con aplasia medular severa, no tributarios a terapia triple inmunosupresora ni trasplante de médula ósea. Aspectos Generales: La trombopeyetina es un factor humoral o citoquina, el cual estimula la producción de trombocitos (plaquetas), proliferación de megacariocitos de la médula ósea y por ende liberación de plaquetas en un mecanismo llamado trombopoyesis. El rol principal de las plaquetas es proveer la interacción y activación de factores de coagulación en la cascada de coagulación. Los pacientes con anemia aplásica exhiben altos niveles de trombopoyetina y pero aún así presentan trombocitopenia debido a una supresión o falla por parte de la producción de plaquetas en la médula ósea. Tecnología Sanitaria de Interés: Eltrombopag (ETP), Revolade o Promacta (GlaxoSmithKline lnc) es un medicamento agonista del receptor de la trombopoyetina (TPOr) que promueve la diferenciación megacariocítica, la proliferación y la producción de plaquetas. Es un agente hematopoyético que actúa como agonista no peptídico del receptor de la trombopoyetina. Interacciona con el dominio transmembrana e induce a la proliferación y diferenciación de los megacariocitos produciendo, a consecuencia de ello, un incremento en el recuento plaquetario. METODOLOGÍA: Estrategia de Búsqueda: Se llevó a cabo una búsqueda sistemática de la literatura con respecto a la eficacia y seguridad de Eltrombopag en pacientes con aplasia medular severa, no tributarios a terapia triple inmunosupresora ni trasplante de médula ósea. Para la búsqueda primaria se revisó en primer lugar la información disponible por entes reguladoras y normativas de autorización comercial como la Administración de Drogas y Alimentos (FDA) de Estados Unidos, la Agencia de Medicamentos Europea (EMA) y la Dirección General de Medicamentos y Drogas (DIGEMID) en el Perú. Seguidamente, se emplearon los motores de búsqueda de los metabuscadores Translating Research into Practice (TRIPDATABASE), Epistemonikos y Health Systems Evidence (HSE). Asimismo, se buscó información generada por grupos internacionales que realizan revisiones sistemáticas, evaluaciones de tecnologías sanitarias y guías de práctica clínica, tales como el National Institute for Health and Care Excellence (NICE) del Reino Unido, National Guideline Clearinghouse (NGC) de Estados Unidos, Canadian Agency for Drugs and Technologies in Health (CADTH) de Canadá, Scottish Medicines Consortium (SMC) de Escocia, Haute Authorité de Santé (HAS) de Francia, el Instituto de Evaluación de Tecnologías Sanitarias (IETS) de Colombia, el Instituto de efectividad clínica y sanitaria (IECS) de Argentina. Finalmente, se realizó una búsqueda dentro de las bases de datos Pubmed, EMBASE, y The Web of Science que a su vez fue complementada con una búsqueda en www.clinicaltrials.gov y www.clinicaltrialsregister.eu. RESULTADOS: Sinopsis de la Evidencia: De acuerdo con la pregunta PICO, se llevó a cabo una búsqueda de evidencia científica relacionada al uso de eficacia y seguridad de eltrombopag en pacientes con aplasia medular severa, no tributarios a terapia triple inmunosupresora ni trasplante de médula ósea. En la presente sinopsis se describe la evidencia encontrada a la fecha. Guías de práctica clínica: No se encontraron guías de práctica clínica de buena calidad que recomienden eltrombopag en AAS. Evaluaciones de tecnologías sanitarias: El grupo evaluador de NICE revisó este año (2016) la evidencia disponible para AAS con eltrombopag. Sin embargo es observable que tanto la CADTH de Canada, la SMC de Escocia, el IECS Argentina, IETS Colombia, y la HAS de Francia los cuales son referentes internacionales de evaluaciones de tecnologías sanitarias, no han realizado aún evaluaciones ni han emitido recomendaciones para el uso de eltrombopag en AAS. Ensayos clínicos: Se encontraron los ensayos clínicos fase II de Olnes et al., 2012 y Desmond et al., 2014. Ensayos clínicos no-publicados: Se encontraron tres estudios en progreso en la página de clinicaltrials.gov que corresponden a NCT01891994, NCT 01703169, y NCT 02148133. Otros documentos adicionales: Documento de recomendación como Guía de la BCSH. CONCLUSIONES: El presente dictamen responde a la solicitud de evaluación de tecnología sanitaria del uso fuera del petitorio de Eltrombopag en pacientes con aplasia medular severa, no tributarios a terapia triple inmunosupresora ni trasplante de médula ósea. Se encontraron dos ensayos clínicos fase II, no-aleatorizados, abiertos y de un solo brazo y tres ensayos clínicos en proceso no-publicados, los cuales evaluaron la respuesta hematológica a eltrombopag en la población de interés. La evidencia generada por éstos contiene limitaciones severas para la interpretación y generalización de los resultados para la población de interés. El Instituto de Evaluación de Tecnologías en Salud e Investigación ­IETSI, aprueba el uso de Eltrombopag en pacientes con aplasia medular severa, no tributarios a terapia triple inmunosupresora ni trasplante de médula ósea. La vigencia del presente dictamen preliminar es de un año. En los subsiguientes meses a la publicación del presente dictamen, se evaluará la nueva evidencia publicada en la literatura internacional, y se analizarán los datos clínicos de todos aquellos pacientes que hayan recibido eltrombopag en el contexto del presente dictamen, con el fin de establecer el impacto del mismo. Esta información será tomada en cuenta para actualizar el presente dictamen al culminar su vigencia.

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.

Utilização do gel de clorexidina em crianças com hiperplasiagengival induzida pela ciclosporina / Use of chlorhexidine gel in children with cyclosporine-induced gingival hyperplasia

Crianças que apresentam insuficiência hepática e transplante de fígado tem uma condição sistêmica comprometida. Algumas alterações bucais podem ocorrer nessas crianças, inclusive hiperplasia gengival. OBJETIVO: Utilizar um gel de clorexidina para controlar e minimizar a hiperplasia gengival ocasionada pelo uso de ciclosporina associada a corticosteróide. RELATO DO CASO: Em uma criança de 2 anos e 8 meses, submetida a transplante de fígado com prescrição de ciclosporina associada à corticosteróide, que apresentava hiperplasia gengival em que a opção de remoção cirúrgica do aumento gengival não foi autorizada, foi aplicado gel inibidor de placa clorexidina, uma vez por semana durante quatro semanas. CONSIDERAÇÕES FINAIS: O gel de clorexidina mostrou-se eficaz como auxiliar na terapêutica de impedir a hiperplasia gengival...

Oroantral communication is a pathological communication that occurs between the oral cavity and the maxillary sinus. When this communication suffers epithelialization it is called oroantral fistula. It can occur mainly after extraction of posterior maxillary teeth, due to the close relationship between their roots and the maxillary sinus floor. Aim: To present the surgical options for the treatment of oroantral communication and report a case of a large oroantral fistula, explaining the technique step. Case Report: Female patient female, 37-year-old, presented bucossinusal fistula in the left upper molars area and was surgically treated for its closure. Under local anesthesia an incision was made around the fistula, cutting epithelial tissue to allow the union of the wound edges, and it was sutured by layers: initially sinus mucosa with 4-0 catgut and then the gums, with nylon. The suture was removed 10 days later and by this time the complete closure of the fistula was observed. Conclusion: The decision of which treatment modality to use for oroantral communication is influenced by many factors, such as its size, the tissue conditions and the surgeon’s skills. The surgical technique presented in this case proved effective and easy to perform, with a confortable postoperative period for the patient and with no recurrence of the communication...

Stepwise Treatment Using Corticosteroids Alone and in Combination with Cyclosporine in Korean Patients with Idiopathic Membranous Nephropathy

PURPOSE: We undertook an observational study to investigate the effects of immunosuppressive treatment on proteinuria and renal function in 179 Korean idiopathic membranous nephropathy patients with nephrotic syndrome. MATERIALS AND METHODS: The primary outcome was regarded as the first appearance of remission and the secondary outcomes as a decline in estimated glomerular filtration rate (eGFR) >50% or initiation of dialysis, and all-cause mortality. Seventy-two (40.2%) and 50 (27.9%) patients were treated with corticosteroids alone (C) and corticosteroids plus cyclosporine (C+C), respectively, whereas 57 (31.8%) did not receive immunosuppressants (NTx). Cyclosporine was added if there was no reduction in proteinuria of >50% from baseline by corticosteroids alone within 3 months. RESULTS: There were no differences in baseline renal function and the amount of proteinuria among the three groups. Overall, complete remission (CR) was achieved in 88 (72.1%) patients by immunosuppressants. In a multivariate analysis adjusted for covariates associated with adverse renal outcome, the probability of reaching CR was significantly higher in the C [hazard ratio (HR), 4.09; p<0.001] and C+C groups (HR, 2.57; p=0.003) than in the NTx group. Kaplan-Meier analysis revealed that 5-year CR rates of C, C+C, and NTx groups were 88.5%, 86.2%, and 56.7% (p<0.001). Ten-year event-free rates for the secondary endpoints in these three groups were 91.7%, 79.9%, and 57.2% (p=0.01). CONCLUSION: Immunosuppressive treatment was effective in inducing remission and preserving renal function in these patients. Therefore, stepwise treatment using corticosteroids alone and in combination with cyclosporine is warranted in these patients.

Agrandamientos gingivales inducidos por fármacos / Drug-induced gingival enlargements

El término agrandamiento gingival por fármacos se refiere a un crecimiento anormal de la encía, secundario al uso de una medicación sistémica. Si bien se reporta una larga lista de medicamentos relacionados, se encontró una fuerte asociación sólo con la Fenitoína , la Nifedipina y la Ciclosporina A. La prevalencia del Agrandamiento Gingival varía ampliamente, sin embargo la prevalencia relacionada con el uso de la Fenitoína es aproximadamente del 50 por ciento. La Nifedipina y la ciclosporina producen cambios en el 25 por ciento de los pacientes tratados. Existe controversia entre la dosis y el riesgo o severidad del Agrandamiento.El grado de Agrandamiento gingival parece estar relacionado con la susceptibilidad del paciente y el grado dehigiene bucal de éste. Después de 1 a 3 meses de iniciada la medicación del fármaco los agrandamientos originadosen la papila interdental, se expande afectando otras áreas de la encía llegando a cubrir en casos extremosuna porción importante de los dientes principalmente en los segmentos anteriores por vestibular. El uso discontinuo de la medicación por el médico de cabecera y más aún la sustitución del fármaco por otroresulta en la regresión y el cese del Agrandamiento.

Risco cardiovascular em pacientes submetidos ao transplante hepático / Cardiovascular risk in patients submitted to liver transplantation

OBJETIVO: Determinar a prevalência de risco cardiovascular em pacientes submetidos ao transplante hepático de acordo com o escore de Framingham e avaliar possíveis associações com fatores de risco tradicionais e não tradicionais. MÉTODOS: Estudo transversal em que pacientes submetidos ao transplante hepático foram estratificados quanto ao risco cardiovascular pelo escore de Framingham. Variáveis demográficas, socioeconômicas, clínicas e antropométricas foram coletadas para verificar associação com risco cardiovascular utilizando-se análises estatísticas uni e multivariada. RESULTADOS: Foram avaliados 115 pacientes, dos quais 46,1% apresentaram médio ou alto risco para ocorrência de eventos cardiovasculares em 10 anos. O risco percentual médio dos pacientes avaliados foi de 9,5% ± 7,8%. Sexo masculino (OR: 4,97; IC 95% 1,92-12,85; p < 0,01), idade avançada (OR: 1,09; IC 95% 1,04-1,13; p < 0,01) e maior IMC no momento da avaliação (1,09; IC 95% 0,99-1,20; p = 0,03) foram fatores associados ao médio e ao alto riscos cardiovasculares. Maior percentual de risco cardiovascular também esteve associado ao uso de ciclosporina (p = 0,01). CONCLUSÃO: A probabilidade de ocorrência de evento cardiovascular nos pacientes submetidos ao transplante hepático avaliados é superior à da população brasileira. Atenção especial deve ser dedicada a essa população, principalmente em relação aos fatores potencialmente modificáveis associados como maior IMC e uso de ciclosporina.

OBJECTIVE: To determine the prevalence of cardiovascular risk in patients undergoing liver transplantation according to the Framingham score, and to evaluate possible associations with traditional and non-traditional risk factors. METHODS: Cross-sectional study in which patients undergoing liver transplantation were stratified by cardiovascular risk according to the Framingham score. Demographic, socioeconomic, clinical, and anthropometric variables were collected to assess the association with cardiovascular risk factors using univariate and multivariate statistical analyses. RESULTS: A total of 115 patients were evaluated, of which 46.1% showed medium or high risk for the occurrence of cardiovascular events over ten years. The mean percentage risk of evaluated patients was of 9.5 ± 7.8%. Male gender (OR: 4.97; CI: 1.92-12.85; p < 0.01), older age (OR: 1,09; CI: 1.04-1.13; p < 0.01), and higher BMI at the moment of assessment (1.09; CI: 0.99-1.20; p = 0.03) were factors associated with medium and high cardiovascular risk. A higher percentage of cardiovascular risk was also associated with cyclosporine use (p = 0.01). CONCLUSION: The probability of occurrence of cardiovascular events in the assessed patients undergoing liver transplantation was higher than that in the Brazilian population. Special attention should be paid to this population, especially in relation to potentially modifiable factors associated to higher BMI and cyclosporine use.

Beneficial effect of ubiquinol, the reduced form of coenzyme Q10, on cyclosporine nephrotoxicity

BACKGROUND: Cyclosporine (CyA) nephrotoxicity is partly due to some oxidative stress. Ubiquinol, the reduced form of coenzyme Q10 (rCoQ10), has recently gained attention for its anti-oxidative potential. The aim of this study is to evaluate the effect of rCoQ10 on a CyA nephrotoxic rat model. MATERIALS AND METHODS: Six-week-old male Wistar rats were divided into three groups (five animals each). Group 1 received a medium only. Group 2 received 30 mg/kg/day of CyA only. Group 3 received both the same dose of CyA and 600 mg/kg/day of rCoQ10. CyA and rCoQ10 were both given orally for four weeks. Systolic blood pressure (BP), daily urinary albumin secretion (u-Alb), serum creatinine (s-Cr) level, and super-oxide anion (SO) level in the renal tissue were measured and compared among those three groups. Immunohistochemistry using an antibody for the transforming growth factor-beta (TGF-beta) was also examined. RESULTS: BPs, u-Albs, s-Crs, and SO levels of groups 1, 2, and 3 were 114 ± 3, 132 ± 4, and 129 ± 5 mmHg, 2.6 ± 0.5, 42.1 ± 7.2, and 22.8 ± 3.4 micro-g/day, 1.1 ± 0.2, 1.7 ± 0.2, and 1.3 ± 0.2 mg/dl, and 224 ± 84, 1251 ± 138, and 512 ± 109 RLU/g kidney respectively. U-Albs, s-Crs, and SO levels were significantly ameliorated by rCoQ10. Micro-vacuolar changes and TGF-beta positive deposits in the proximal renal tubular cells of CyA group rats disappeared in those of CyA and rCoQ10 group rats. CONCLUSION: RCoQ10, an antioxidants, may have potential for preventing CyA nephrotoxicity.

Low prevalence of gingival overgrowth associated to new imunossupressive protocols with cyclosporin

Gingival overgrowth (GO) is a frequent finding in patients treated with cyclosporine (CsA). This study investigated the prevalence and severity of GO in patients who received kidney transplant and CsA therapy, as well as associations with pharmacological and clinical factors. This cross-sectional study included 63 kidney transplant recipients who were treated with CsA in a university hospital. Demographic, pharmacological, and periodontal data were collected. The primary variable was GO. Independent sample t- and chi-square tests were used to compare means in groups with versusl without GO. The response rate was 86.3%. Overall, 40% of patients had some degree of GO. Eleven individuals presented GO scores > 10%, and 5 individuals reached 30%. The mean GO percentage was low (6.79 ± 15.83). Patients that were concurrently under nifedipine treatment showed a non-significant trend toward a greater prevalence of GO. Mean CsA dosage and serum levels were 3.20 ± 0.94 mg/kg/d and 156.12 ± 162.75 ng/mL, respectively. There were no statistically significant differences between patients with versusl without GO nor between the groups receiving nifedipine, no drug, or verapamil. The GO prevalence and severity rates were lower than those reported in previous studies and seemed to be independent of drug interactions.

Nonrejection pathology of renal allograft biopsies: 10 years experience from a tertiary care center in north India.

Background: Renal dysfunction in allograft transplant is common and its assessment is done using Revised Banff '97 working classification, which is the accepted formulation for the evaluation of histological appearance of renal allograft biopsies. The nonrejection category under the Banff working classification of renal allograft pathology forms a large group resulting in allograft dysfunction. Aim: To evaluate the spectrum of histopathological changes seen in renal allograft dysfunction. Materials and Methods: A total of 119 renal biopsies were studied over 10 years presenting with renal allograft dysfunction from a tertiary center in North India. Results: Majority of the biopsies were in the nonrejection category (47.1%), which included few cases of acute tubular necrosis (25.2%), cyclosporine nephrotoxicity (16%), infections (10.9%), and thrombotic microangiopathy (3.4%). The second largest category in our study was acute/active cellular rejection group (31.9%), which displayed moderate to severe tubulitis, mononuclear cell infiltrate in the interstitium, and vasculitis. Antibody-mediated rejection cases were seen in 28.6% of the renal biopsies followed by chronic allograft nephropathy cases (12.6%) showing features of tubular atrophy and interstitial fibrosis. Borderline changes with features of mild tubulitis contributed to 7.6% of the biopsies. The smallest group comprised of only 4.2%, which were within normal histological limits. Conclusion: Timely accurate diagnosis of renal allograft dysfunction is essential for prompt, effective management of renal transplant patients. Thus, nonrejection pathology forms a significant cause of renal dysfunction in patients with renal allograft transplantation.

Cyclosporine therapy for autoimmune hepatitis in children

The current immunosuppressive treatment of patients with autoimmune hepatitis [AIH] consists of prednisolone and azathioprine. Higli doses of prednisolone used for disease remission are not universally effective and have serious adverse effects. Some authors have provided evidence of AIH therapy in children and adults with cyclosporine [Neoral] should corticosteroid therapy become ineffective. Preliminary results using cyclosporine in a small group of patients have shown that this drug appears to be a good substitute for corticosteroids. We performed this study to assess the efficacy and safety of cyclosporine in induction of remission in children with AIH. This was a case series, interventional clinical trial that involved children with AIH. twelve children with a median age of 9 years, 3 months who were diagnosed according to international criteria as having definite AIH were recruited. Cyclosporine alone was administered at a dosage of 3.5-5 mg/kg in 3 daily doses for 5 months, followed by low dose prednisolone [0.3 mg/kg/d] for one month, then followed by combined low doses of prednisolone and azathioprine [1.5 mg/kg/d in two doses]. Patients discontinued cyclosporine after seven months. Biochemical remission of the disease was established by assessment of serum transaminase activity levels. Growth parameters that included Z-scores for height and weight, and adverse effects of the treatment were recorded, Of the 10 remaining patients, 7 had normalized alanine aminotransferase [ALT] activity levels by 4 months and all patients had normalized ALT levels by 9 months of treatment. Adverse effects of cyclosporine were mild and disappeared during weaning off the medication. Cyclosporine induced biochemical remission of the hepatic inflammatory/necrotic process in children with AIH. There were few, well-tolerated adverse effects. Longer follow-up of patients is necessary to establish possible long-term toxicity of cyclosporine