Targeted therapies for lupus nephritis: Current perspectives and future directions / 中华医学杂志(英文版)

Lupus nephritis (LN), a severe manifestation of systemic lupus erythematosus, poses a substantial risk of progression to end-stage renal disease, with increased mortality. Conventional therapy for LN relies on broad-spectrum immunosuppressants such as glucocorticoids, mycophenolate mofetil, and calcineurin inhibitors. Although therapeutic regimens have evolved over the years, they have inherent limitations, including non-specific targeting, substantial adverse effects, high relapse rates, and prolonged maintenance and remission courses. These drawbacks underscore the need for targeted therapeutic strategies for LN. Recent advancements in our understanding of LN pathogenesis have led to the identification of novel therapeutic targets and the emergence of biological agents and small-molecule inhibitors with improved specificity and reduced toxicity. This review provides an overview of the current evidence on targeted therapies for LN, elucidates the biological mechanisms of responses and failure, highlights the challenges ahead, and outlines strategies for subsequent clinical trials and integrated immunomodulatory approaches.

Effect of mycophenolate mofetil alleviates carbon tetrachloride-induced liver fibrosis in mice / 中南大学学报(医学版)

OBJECTIVES@#Hepatic fibrosis is a serious pathological consequence of chronic liver disease. Mycophenolate mofetil (MMF) is a commonly used immunosuppressant after organ transplant. However, the relationship between MMF and hepatic fibrosis remains unclear. This study aims to explore the effect of MMF on hepatic fibrosis in mice and the potential mechanism.@*METHODS@#A total of 24 mice (male, 8-week old, C57BL/6) were randomly divided into a control group, a MMF group, a carbon tetrachloride (CCl4) group and a CCl4+MMF group (n=6 in each group). After the mice were sacrificed, the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were detected. The liver tissues were taken up for Masson staining and collagen I (COL1) immunohistochemistry. The levels of transforming growth factor-β1 (TGF-β1) and α-smooth muscle actin (α-SMA) were detected by Western blotting. Finally, the levels of mRNA for TGF-β1, α-SMA, and COL1 were detected using real-time PCR.@*RESULTS@#Compared with the CCl4 group, the ALT and AST levels were lower (both P<0.05), the degree of liver fibrosis was alleviated, and the deposition of COL1 in the liver was significantly decreased (P<0.01) in the CCl4+MMF group. Compared with the CCl4 group, the protein expression levels of TGF-β1 and α-SMA were significantly decreased (both P<0.05) and the relative expression levels of TGF-β1, α-SMA and COL1 mRNA in the liver were significantly decreased (all P<0.05) in the CCl4+MMF.@*CONCLUSIONS@#MMF could reduce CCl4-induced hepatic fibrosis, which might be related to the inhibition of TGF-β1. This study is expected to provide a target for the treatment of hepatic fibrosis.

Therapeutic effect of mycophenolate mofetil or cyclophosphamide in children with Henoch-Schönlein purpura nephritis of different age groups / 中国当代儿科杂志

OBJECTIVES@#To investigate the difference in the therapeutic effect of mycophenolate mofetil (MMF) or cyclophosphamide (CTX) in children with Henoch-Schönlein purpura nephritis (HSPN) of different age groups.@*METHODS@#A retrospective analysis was conducted on the clinical data of 135 children with HSPN who were treated with MMF or CTX in the Department of Nephrology, Children's Hospital Affiliated to Capital Institute of Pediatrics, from October 2018 to October 2020. According to the immunosuppressant used, they were divided into two groups: MMF group and CTX group, and according to the age, each group was further divided into two subgroups: ≤12 years and >12 years, producing four groups, i.e, the ≤12 years MMF subgroup (n=30), the >12 years MMF subgroup (n=15), the ≤12 years CTX subgroup (n=71), and the >12 years CTX subgroup (n=19). All children were followed up for at least 12 months, and the above groups were compared in terms of clinical outcomes and the incidence rate of adverse reactions.@*RESULTS@#There was no significant difference in the complete response rate between the MMF group and the CTX group after 3, 6, and 12 months of treatment (P>0.05). There were no significant difference in the complete response rate and the incidence rate of adverse reactions between the >12 years MMF subgroup and the ≤12 years MMF subgroup at 3, 6, and 12 months of treatment (P>0.05). The >12 years CTX subgroup had a significantly lower complete response rate than the ≤12 years CTX subgroup at 6 and 12 months of treatment (P<0.05). The >12 years CTX subgroup had a significantly higher incidence rate of adverse reactions than the >12 years MMF subgroup (P<0.05).@*CONCLUSIONS@#The efficacy and adverse reactions of MMF are not associated with age, but the efficacy of CTX is affected by age, with a higher incidence rate of adverse reactions. CTX should be selected with caution for children with HSPN aged >12 years.

Clinical effect of different immunosuppressive treatment regimens in children with ocular myasthenia gravis: a retrospective analysis / 中国当代儿科杂志

OBJECTIVES@#To investigate the clinical effect of different immunosuppressive treatment regimens in children with ocular myasthenia gravis (OMG).@*METHODS@#A retrospective analysis was conducted on 130 children with OMG who were treated in the Department of Neurology, Jiangxi Children's Hospital, from February 2018 to February 2023. According to the treatment regimen, they were divided into four groups: glucocorticoid (GC) group (n=29), mycophenolate mofetil (MMF) group (GC+MMF; n=33), methotrexate (MTX) group (GC+MTX; n=30), and tacrolimus (FK506) group (GC+FK506; n=38). Treatment outcomes and adverse reactions were compared among the groups.@*RESULTS@#After 3 months of treatment, the FK506 group had significantly lower scores of Myasthenia Gravis Quantitative Scale and Myasthenia Gravis-Specific Activities of Daily Living than the other three groups (P<0.05). After 3 months of treatment, the FK506 group had a significantly lower dose of prednisone than the GC group, and after 6 and 9 months of treatment, the MMF, MTX, and FK506 groups had a significantly lower dose of prednisone than the GC group (P<0.05). After 12 months of treatment, the MMF, MTX, and FK506 groups had a significantly lower incidence rate of GC-related adverse reactions than the GC group (P<0.05).@*CONCLUSIONS@#For children with OMG, the addition of various immunosuppressants can reduce the dosage of GC and adverse reactions. Among them, FK506 shows superior efficacy compared to other immunosuppressants in the early treatment of OMG.

Uso de micofenolato mofetilo fuera de registro en enfermedades inmunomediadas / Off-label use of mycophenolate mofetil in immune-mediated diseases

BACKGROUND: Mycophenolate mofetil (MMF) is a largely used immunosuppressive agent in the prevention of transplant rejection and lupus nephritis. Its use has been extended to other immune-mediated diseases (ID). AIM: To assess the off-label use of MMF, its performance as a glucocorticoid sparing agent, the therapeutic response, and its adverse effects. MATERIAL AND METHODS: A retrospective study was performed. One hundred-seven patients aged 58 ± 16 years (83% females) who received MMF for ID in off label uses between 2016 and 2018 were included. The study variables were cause of MMF indication, sex, age, use as a first- or second-line treatment and maintenance dosing. The cumulative doses of glucocorticoids six months before and after MMF indication were compared. RESULTS: MMF was used as a second-line therapy in 66 patients (62%). The mean maintenance dose of MMF was 1,500 ± 540 mg/day. Prednisone cumulative doses were 3,908 ± 2,173 and 1,672 ± 1,083 milligrams six months before and six months after starting MMF, respectively (p < 0.01). Adverse effects were identified in 21 (20%) cases, none of them serious. CONCLUSIONS: Mycophenolate has a favorable response profile as a second line immunosuppressive agent. It is effective as a glucocorticoid sparing drug. The safety profile is also favorable as adverse effects were scanty and mild.

Análise de custo-efetividade do uso de inibidores da via de sinalização mTOR x micofenolato em receptores de transplante renal sem profilaxia para citomegalovírus s / Cost-effectiveness analysis of the use of mTOR signaling pathway inhibitors x mycophenolate in kidney transplantation recipients without cytomegalovirus prophylaxis

Objetivo: Avaliar a relação de custo-efetividade dos regimes imunossupressores utilizados em pacientes receptores de transplante renal, no Hospital Santa Casa de Misericórdia de Juiz de Fora, MG, basiliximabe, micofenolato de sódio, tacrolimo e prednisona (Grupo 1 = 93 pacientes), comparados com a associação de timoglobulina, everolimo, tacrolimo e prednisona (Grupo 2 = 91 pacientes). Métodos: Para a análise farmacoeconômica, foi utilizado o modelo de Árvore de Decisão, desenvolvido no software Treeage Suite 2011. Foi considerada uma coorte real de pacientes submetidos ao transplante renal entre janeiro de 2013 e março de 2017, os quais foram acompanhados por um período de um ano, sendo mensurados os benefícios clínicos, bem como os custos associados, na perspectiva do Sistema Único de Saúde. O método de custeio utilizado foi o botton-up. Foram adotados os limiares de custo-efetividade (LCEs) equivalentes a 1 PIB per capita e 1 a 3 PIB, considerando o ano de 2017. Resultados: No que diz respeito à sobrevida, a RCEI foi de cerca de R$ 214.234,12 para 1 ano de vida ganho. Em relação aos eventos adversos, a RCEI foi de cerca de R$ 43.682,98 para 1 ano sem incidência de eventos adversos. Conclusões: Ao avaliar a sobrevida e a incidência de eventos adversos, timoglobulina+everolimo não é considerado custo-efetivo em relação ao esquema contendo basiliximabe+micofenolato de sódio diante do LCE de 1 PIB per capita. No entanto, ao adotarmos o LCE até 3 PIB per capita, o regime contendo moglobulina+everolimo é custo-efetivo, ultrapassando cerca de 38% do PIB per capita.

Objective: Evaluate the cost-effectiveness of immunosuppressive regimens used in kidney transplant recipients at the Santa Casa de Misericórdia, Hospital in Juiz de Fora, MG, compared with basiliximab, mycophenolate sodium, tacrolimus and prednisone (Group 1 = 93 patients) with the association of thymoglobulin, everolimus, tacrolimus and prednisone (Group 2 = 91 patients). Methods: For the pharmacoeconomic analysis, the Decision Tree model was used, developed in the TreeAge Suite 2011 software. A real cohort of patients undergoing kidney transplantation between January 2013 and March 2017 was considered, they were followed up for a period of 1 year, where the clinical benefits were measured, as well as the associated costs, from the perspective

Pharmacogenomics of mycophenolic acid in kidney transplantation: Contribution of immune response-related genes

Abstract Mycophenolic acid (MPA) inhibits IMPDH, involved in the guanosine nucleotides synthesis, and prevents DNA replication in immune cells. The repression of cell and humoral immunity by MPA induces allograft tolerance preventing acute rejection in solid organ transplantation. MPA is an effective and safe drug, but genetic and non-genetic factors have been implicated in the interindividual variability of drug response. Several studies have shown the impact of variants of pharmacokinetics or pharmacodynamics-related genes on MPA response in kidney transplantation. This review explored further the influence of genes involved in the immune response on clinical outcomes of kidney recipients on short- or long-term MPA treatment. Variants in genes related to T cell activation (CD28, CTL4, ICOS, PDPC1), pro-inflammatory cytokines (IL2, IL6, IL12A, IL12B, TNF, IFNG), immunomodulatory cytokines (IL4, IL10, TGFB1), and innate immune response (CD14, TLR2, TLR4) were shown to be associated with increased risk of acute rejection, graft function or survival, chronic graft nephropathy, viral infections or MPA-induced myelotoxicity. Some of the significant pharmacogenetic associations were confirmed by meta-analyses of kidney transplantation. These findings are suggestive that variants in immune response-related genes contribute to the variability of MPA response, and have potential application as biomarkers of acute rejection in kidney transplantation.

Lesiones ampollares en una paciente con morfea panesclerótica discapacitante de la infancia / Bullous lesions in a patient with panesclerotic morphea of the childhood

La morfea ampollar es un tipo enfrecente de esclerodermia localizada que se caracteriza por presentar ampollas sobre placas escleróticas. La presencia de este tipo de lesiones obliga a descartar la variante extraenital de liquen esclerodemias localizadas, es posible hallar ambas afecciones. Se describe el caso de una paciente de 19 años con diagnóstico de morfea panesclerótica y liquen escleroso ampollar.

Bollous morphea is an infreqent type of morphea characterized for developing bullae on sclerodermiformic plaques. The presence of bullae forces to discard lichen sclerosus, a disease that usually develops in the genital zone, the extragenital variant could belong to the same spectrum that localized sclerodermiformic diseases. We present a 19 year old female patient with the diagnosis of panesclerotic morphea and bullous lichen sclerosus.

Thromboelastometry assessment of mycophenolate mofetil effect on thrombotic risk in dogs with primary and secondary immune-mediated hemolytic anemia and by Erhlichia canis infection / [Avaliação por tromboelastometria do efeito do micofenolato de mofetila no risco trombótico em cães com anemia hemolítica imunomediada primária e secundária à infecção por Erhlichia canis]

This study aimed to identify, by means of thromboelastometry assessment, altered thrombotic risk in dogs with primary and secondary IMHA by E. canis infection after initiating the immunosuppressive therapy with mycophenolate mofetil. The animals' screening was based on complete blood count (CBC), biochemical and urine tests. Dogs with moderate to severe anemia (hematocrit ≤ 25%) which showed symptoms of immune-mediated hemolysis, such as spherocytosis, positive saline agglutination, bilirubinuria and/or hemoglobinuria, were included. Blood and urine samples were collected at two different moments. The first sample (M1) was collected at the time of diagnosis, when hematocrit was lower or equal to 25% before treatment with mycophenolate mofetil (Accord ®); the second sample (M2) was collected after treatment with mycophenolate mofetil, when hematocrit was greater or equal to 30%. Five out of the twelve animals selected died before the end of the study. No reduction in thrombotic risk was observed in the animals treated with mycophenolate mofetil. The animals that presented hypocoagulation at the time of diagnosis showed the worst prognosis, and their reticulocyte count displayed a better prognostic value than their erythrocytes count at the time of diagnosis.(AU)

O objetivo deste estudo foi esclarecer se há alteração do risco trombótico em cães com anemia hemolítica imunomediada primária e secundária a E.canis, avaliado por meio da tromboelastometria, após início de tratamento com micofenolato de mofetila. A seleção dos animais foi baseada na avaliação de hemograma, exame bioquímico e urinálise. Cães com anemia moderada a severa (hematócrito ≤ 25%), com sinais de hemólise imunomediada, como esferocitose, aglutinação em salina positivo, bilirrubinúria e/ ou hemoglobinúria, foram incluídos. As amostras de sangue e urina foram coletadas em dois momentos diferentes. A primeira amostra (M1) foi coletada no momento do diagnóstico, quando o hematócrito era igual ou inferior a 25%, sem fazer uso do micofenolato de mofetila (Accord®), e o segundo momento (M2), após tratamento com micofenolato de mofetila, quando o hematócrito era igual ou maior que 30%. Doze animais foram selecionados, cinco morreram antes do término do estudo. Não houve diminuição do risco trombótico entre os animais tratados com micofenolato de mofetila; os animais que apresentaram menor coagulabilidade apresentaram pior prognóstico, e a contagem de reticulócitos apresentou melhor valor prognóstico do que a contagem de hemácias no momento do diagnóstico.(AU)

Efficacy and safety of mycophenolate mofetil versus cyclophosphamide in the treatment of Henoch-Schönlein purpura nephritis with nephrotic-range proteinuria in children: a prospective randomized controlled trial / 中国当代儿科杂志

OBJECTIVE@#To study the efficacy and safety of mycophenolate mofetil (MMF) versus cyclophosphamide (CTX) in the treatment of children with Henoch-Schönlein purpura nephritis (HSPN) and nephrotic-range proteinuria.@*METHODS@#A prospective clinical trial was conducted in 68 pediatric patients who were admitted to the Department of Nephrology, Children's Hospital Affiliated to Capital Institute of Pediatrics and who were diagnosed with HSPN and nephrotic-range proteinuria from August 2016 to November 2019. The patients were randomly divided into two groups:MMF treatment (@*RESULTS@#At months 3, 6, and 12 of treatment, there was no significant difference in the complete remission rate and the response rate between the MMF treament and CTX treatment groups (@*CONCLUSIONS@#MMF and CTX have similar efficacy and safety in the treatment of HSPN children with nephrotic-range proteinuria.

Safety and effectiveness of mycophenolate mofetil associated with tacrolimus for liver transplantation immunosuppression: a systematic review and meta-analysis of randomized controlled trials

A combination of immunosuppressants may improve outcomes due to the synergistic effect of their different action mechanisms. Currently, there is no consensus regarding the best immunosuppressive protocol after liver transplantation. This review aimed to evaluate the effectiveness and safety of tacrolimus associated with mycophenolate mofetil (MMF) in patients undergoing liver transplantation. We performed a systematic review and meta-analysis of randomized clinical trials. Eight randomized trials were included. The proportion of patients with at least one adverse event related to the immunosuppression scheme with tacrolimus associated with MMF was 39.9%. The tacrolimus with MMF immunosuppression regimen was superior in preventing acute cellular rejection compared with that of tacrolimus alone (risk difference [RD]=-0.11; p =0.001). The tacrolimus plus MMF regimen showed no difference in the risk of adverse events compared to that of tacrolimus alone (RD=0.7; p=0.66) and cyclosporine plus MMF (RD=-0.7; p=0.37). Patients undergoing liver transplantation who received tacrolimus plus MMF had similar adverse events when compared to patients receiving other evaluated immunosuppressive regimens and had a lower risk of acute rejection than those receiving in the monodrug tacrolimus regimen.

Neumonía intersticial con características autoinmunes: reporte de caso / Interstitial Pneumonia with Autoimmune Features: case report

La neumonía intersticial con características autoinmunes por sus siglas en inglés, es una entidad en la que existe un compromiso pulmonar intersticial y hallazgos clínicos y paraclínicos que sugieren una enfermedad del tejido conectivo, aunque no cumplen criterios diagnósticos para ninguna de estas. Con fines de investigación, en el 2015 se describieron criterios para esta entidad, en los que se incluyeron características de los dominios clínicos, serológicos y morfológicos, con diversos patrones de compromiso pulmonar. En la actualidad, hay un aumento en el interés de esta entidad, pues algunos autores sugieren que se pueda tratar de una enfermedad autoinmune per se, cuyo órgano blanco principal sería el pulmón. Dado su reciente reconocimiento, son pocos los casos descritos en la literatura. Con el propósito de contribuir a la mejor identificación de esa entidad, presentamos el caso de una paciente de 68 años con afectación pulmonar en quien después de descartar otras causas se llegó al diagnóstico de neumonía intersticial con características autoinmunes al cumplir los criterios de cada dominio requerido. Se inició tratamiento con micofenolato mofetilo a dosis de 2,5 mg/día. En su evolución clínica, la paciente presentó mejoría y fue dada de alta con tratamiento ambulatorio(AU)

Interstitial pneumonia with autoimmune features is a condition in which patients can have clinical and serological findings suggesting of a connective tissue disease associated with an interstitial lung disease, nonetheless no criteria for an specific connective tissue disease are meeting. In 2015 classification criteria where proposed, the diagnosis is made in the presence of a combination of features from clinical, serological and morphological domain with various patterns of pulmonary involvement. Currently there is an increase in the interest of this condition, as some authors suggest that it can be an autoimmune pathology per se, whose main target organ would be the lung. Given its recent recognition, there are few cases described in the literature and therefore in order to contribute to the better identification of that entity, we present the case of a 65 year old patient with lung involvement in whom after ruling out other etiological causes reached the diagnosis of I Interstitial pneumonia with autoimmune by meeting criteria of each required domain(AU)

Informe diário de evidências COVID-19: busca realizada em 11 de agosto de 2020 / COVID-19 daily evidence report: search conducted on August 11, 2020

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referentes ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 14 artigos e 5 protocolos.

Informe diário de evidências COVID-19: busca realizada em 7 de julho de 2020 / COVID-19 daily evidence report: search conducted on July 7, 2020

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referente ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 17 artigos.

Does the association of tacrolimus and mycophenolate mofetil change the healing of the abdominal wall? study in rats submitted to ischemia and kidney reperfusion / A associação de tacrolimus e micofenolato mofetil altera a cicatrização da parede abdominal? estudo em ratos submetidos à isquemia e reperfusão renal

ABSTRACT Background: Tacrolimus and mycophenolate mofetil are immunosuppressive agents widely used on the postoperative period of the transplants. Aim: To evaluate the influence of the association of them on the abdominal wall healing in rats. Methods: Thirty-six Wistar rats were randomly assigned in three groups of 12. On the early postoperative period, four of the control group and three of the experimental groups died. The three groups were nominated as follow: control group (GC, n=8); group I (GI, n=11, standard operation, mycophenolate mofetil and tacrolimus); group II (GII, n=10, standard operation, mycophenolate mofetil and tacrolimus). The standard operation consisted of right total nephrectomy and 20 min ischemia of the left kidney followed by reperfusion. Both NaCl 0.9% and the immunosuppressive agents were administered starting on the first postoperative day and continuing daily until the day of death on the 14th day. On the day of their deaths, two strips of the anterior abdominal wall were collected and submitted to breaking strength measurement and histological examination. Results: There were no significant differences in wound infection rates (p=0,175), in the breaking strength measurement and in the histological examination among the three groups. Conclusion: The combination of the immunosuppressive agents used in the study associated with renal ischemia and reperfusion does not interfere in the abdominal wall healing of rats.

RESUMO Racional: O tacrolimus e o micofenolato mofetil são imunossupressores amplamente utilizados no pós-operatório dos transplantes de órgãos. Objetivo: Avaliar os efeitos deles sobre a cicatrização da parede abdominal em ratos. Métodos: Foram utilizados 36 ratos Wistar, distribuídos aleatoriamente em três grupos de 12. No pós-operatório imediato, quatro do grupo controle e três do grupo experimentação morreram. Os três grupos receberam as seguintes denominações: grupo controle (GC, n=8); grupo I (GI, n=11, operação-padrão, micofenolato mofetil e tacrolimus); grupo II (GII, n=10, operação-padrão, micofenolato mofetil e tacrolimus). A operação-padrão consistiu de nefrectomia total à direita, isquemia durante 20 min seguida de reperfusão do rim esquerdo. Solução de NaCl 0,9% e micofenolato mofetil + tracolimus foram administradas a partir do 1° dia do pós-operatório e mantidas até o dia do sacrifício dos animais, no 14° dia. Na data do sacrifício, foram retirados dois fragmentos da parede abdominal para análise da resistência à ruptura e exame histológico. Resultados: Não houve diferença estatisticamente significativa no índice de infecção de ferida operatória (p=0,175), nos valores de resistência de ruptura e nos achados histopatológicos entre os três grupos de animais. Conclusão: Os esquemas de imunossupressão empregados associados ao fenômeno da isquemia-reperfusão renal não induzem fraqueza significativa da cicatriz da parede abdominal em ratos no 14° dia de pós-operatório.

Comparación entre dos esquemas de inmunosupresión en pacientes con trasplante hepático en un hospital universitario en Medellín, Colombia / Comparison of two immunosuppressive regimens for liver transplant patients in a university hospital in Medellín, Colombia

Introducción. El desarrollo de terapias inmunosupresoras en trasplante hepático ha sido uno de los aspectos fundamentales que ha permitido disminuir la presencia de rechazos y mejorar la supervivencia del injerto y de los pacientes. El presente estudio se hizo para conocer la efectividad de dos esquemas de tratamiento inmunosupresor en una cohorte de pacientes con trasplante hepático, entre 2006 y 2017, en un hospital universitario en Medellín, Colombia. Metodología. Se realizó un estudio observacional retrospectivo donde se compararon dos esquemas de tratamiento inmunosupresor con ciclosporina (CsA) y azatioprina (AZA) versus tacrolimus (TAC) y micofenolato (MMF). Resultados. Se incluyeron 147 pacientes al estudio, 79 mujeres y 68 hombres, con una mediana de edad de 55 años. La tasa de incidencia de rechazo agudo en el grupo CsA/AZA fue de 7,3 y para el grupo TAC/MMF fue de 13,8, con una razón de tasas de 0,53 (IC95%=0,31-0,89) por cada 100 personas/año, siendo esta diferencia estadísticamente significativa (p=0,02). No hubo diferencias significativas entre los grupos con respecto a la presencia de rechazo crónico, supervivencia del injerto o de los pacientes. Con respecto a los efectos adversos asociados al tratamiento, solo hubo diferencia significativa en una mayor presencia de diarrea en el grupo TAC/MMF. Conclusión. Solo se encontró diferencia significativa en cuanto a un número mayor de rechazos agudos en el grupo tratado con TAC/MMF. Estos hallazgos están en concordancia con la experiencia local, en la que en pacientes seleccionados se puede utilizar este esquema, con buenos resultados clínicos y menores costos para el sistema de salud. Hasta el momento, esta es la primera cohorte retrospectiva de Colombia y Latinoamérica que realiza una comparación, como la expuesta.

Introduction. The development of immunosuppressive therapies in liver transplantation has been one of the major contributing factors that have reduced the presence of rejections and improved graft and patient survival. The present study was conducted to determine the effectiveness of two immunosuppressive schemes in a cohort of liver transplant patients, between 2006 and 2017, at a university hospital in Medellin, Colombia. Methodology. A retrospective observational study was performed to compare two immunosuppressive treatment schemes with cyclosporine (CsA) and azathioprine (AZA) versus tacrolimus (TAC) and mycophenolate (MMF). Results. A total of 147 patients were included in the study, 79 women and 68 men, with a median age of 55 years. The incidence rate of acute rejection in the CsA/AZA group was 7.3 while in the TAC/MMF group was 13.8, with a rate ratio of 0.53 (95%CI=0.31-0.89) for every 100 person-year, this difference being statistically significant (p=0.02). There were no significant differences between the groups regarding the presence of chronic rejection, graft or patient survival. With respect to adverse effects associated with the treatment, there was only a significant difference in the presence of diarrhea in the TAC/MMF group. Conclusion. A significant difference was only found in terms of a higher number of acute rejections in the group treated with TAC/MMF. These findings are in agreement with local experience, in which this scheme can be used in selected patients, with good clinical results and lower costs for the health system. So far, this is the first retrospective study in Colombia and Latin America to make a comparison such as the one presented.

Analysis of the clinical effects of the combination of mycophenolate mofetil with either tacrolimus or cyclophosphamide

OBJECTIVES: Here, we aimed to compare the clinical effects of mycophenolate mofetil combined with either tacrolimus or with cyclophosphamide on lupus nephritis (LN) and to analyze their influence on the expression of cystatin C and on transforming growth factor-1 (TGF-β1). METHODS: A total of 234 patients were randomly divided into two groups: group A, for mycophenolate mofetil combined with tacrolimus (n=117) and group B, for mycophenolate mofetil combined with cyclophosphamide (n=117). The enzyme-linked immunosorbent assay was adopted to detect the expression levels of serum TGF-β1 and cystatin C before and after treatment. RESULTS: The total effectiveness rate in group A was much higher than that in group B. The times of effectiveness and effect validity in group A were much lower than those in group B. The expression levels of serum TGF-β1 and cystatin C decreased slightly after treatment in the two groups, and those of group A were much lower than those of group B. CONCLUSIONS: The combination of mycophenolate mofetil and tacrolimus showed better clinical efficacy on LN and was safer than that of mycophenolate mofetil and cyclophosphamide. Moreover, the drug combination of mycophenolate mofetil and tacrolimus greatly reduced the expression levels of serum TGF-β1 and cystatin C.

Síndrome de Susac: Una causa poco frecuente de encefalopatía / Susac syndrome, a rare cause of encephalopathy

El síndrome de Susac es una enfermedad rara causada por oclusión autoinmune de la microvasculatura del cerebro, de la retina y del oído interno, lo que provoca la triada clínica característica de disfunción del sistema nervioso central, trastornos visuales y déficit vestíbulo-coclear. El diagnóstico se basa en las manifestaciones clínicas y en estudios complementarios que demuestren el compromiso de los tres sistemas. Existen diferentes tratamientos que incluyen combinaciones de varios fármacos inmunosupresores como corticoides, inmunoglobulina intravenosa, micofenolato mofetilo, entre otros. Presentamos el caso de una mujer de 26 años que manifestó hipoacusia izquierda, zumbidos y episodios de vértigo recurrente. Cuatro semanas después agregó visión borrosa bilateral, ataxia cerebelosa y encefalopatía. La resonancia magnética de cerebro mostró múltiples lesiones redondeadas hiperintensas en t2 y FLAIR (fluid-attenuated inversion recovery), hipointensas en t1 a nivel medial del cuerpo calloso, cápsula interna, cerebelo y pedúnculo cerebeloso medio derecho. La audiometría evidenció hipoacusia perceptual bilateral a predominio del oído izquierdo y en la angiografía por tomografía de coherencia óptica se observó obstrucción de arterias de la capa profunda de la retina. Se diagnosticó síndrome de Susac y se inició tratamiento con pulsos de metilprednisolona por 5 días y mantenimiento con micofenolato, revirtiendo totalmente la encefalopatía, con persistencia de leve ataxia e hipoacusia. Es importante conocer la triada clínica característica y los estudios complementarios necesarios para arribar al diagnóstico, ya que muchas veces se puede demorar el tratamiento inmunosupresor. Nuestro caso tuvo una excelente respuesta a los corticoides.

Susac syndrome is a rare disorder caused by autoimmune-mediated occlusions of microvessels in the brain, retina and inner ear. These occlusions lead to a characteristic clinical triad of central nervous system dysfunction, visual disturbances and vestibule-cochlear deficits. The diagnosis is based on clinical manifestations and complementary studies, which demonstrate the involvement of three systems. There are different treatments that include various immunosuppressive drugs combinations such as corticosteroids, intravenous immunoglobulin, mycophenolate mofetil, among others. We present the case of a 26-year-old woman with left hearing loss, tinnitus and episodes of recurrent vertigo, four weeks after bilateral blurred vision, cerebellar ataxia and encephalopathy. Magnetic resonance imaging of the brain showed multiple rounded hyperintense lesions in t2 and fluid-attenuated inversion recovery (FLAIR), hypointense in t1, at the middle level of the corpus callosum, internal capsule, cerebellum and right middle cerebellar peduncle. The audiometry evidenced bilateral perceptual hearing loss, predominantly in the left ear. Angiography by optical coherence tomography showed obstruction in the deep layer retina arteries. The Susac syndrome was diagnosed and treatment started with methylprednisolone pulses therapy, intravenously 1000 mg/ day for 5 days, followed by maintenance with mycophenolate, which completely reversed the encephalopathy, with persistence of mild ataxia and hearing loss. It is important to know the clinical triad characteristic and the complementary studies necessary to arrive at the diagnosis, since immunosuppressive treatment can often be delayed. Our case had an excellent response to corticosteroids.

Comparison of Renal Responses to Cyclophosphamide and Mycophenolate Mofetil used as Induction Therapies in Korean Patients with Lupus Nephritis

OBJECTIVE: Although intravenous cyclophosphamide (IVC) is generally accepted as the standard therapy for induction treatment of active proliferative lupus nephritis (LN), several clinical trials have suggested that mycophenolate mofetil (MMF) is at least as effective as IVC. Because few Asian studies have compared the two treatment modalities, we compared the efficacies of MMF and IVC as LN remission induction treatments in Korean patients. METHODS: We enrolled 39 patients with class III and IV LN who received MMF or IVC as LN induction therapy. The renal outcomes (i.e., complete response [CR], partial response [PR], and no response [NR]) at 6 and 12 months were defined using the ACR 2006 response criteria. RESULTS: Of 39 patients, 23 (59.0%) were treated with IVC, and 16 (41.0%) were treated with MMF. Demographics, clinical characteristics, laboratory data, and adverse events did not significantly differ between the two groups. However, C3 levels were lower and activity scores in renal biopsy were higher in IVC-treated patients. CRs were achieved by 11 (47.8%) of the patients receiving IVC and 7 (43.8%) of the patients receiving MMF after 6 months of treatment (p=0.961) and by 11 (47.8%) of those who received IVC and 9 (56.2%) of those who received MMF at 12 months of treatment (p=0.713). Neither the PR rate nor the NR rate differed significantly at 6 or 12 months between the two groups. CONCLUSION: The efficacy of MMF does not differ from that of IVC in terms of induction of LN remission in Korean patients.