Avaliação de herpesvírus em sangue e saliva de pacientes cirróticos / Evaluation of herpesvirus in blood and saliva of cirrhotic patients

Pacientes cirróticos em fila de transplante hepático possuem inúmeros prejuízos em vias fisiológicas, como a evidente deficiência imune. O dano ao sistema reticuloendotelial, o comprometimento das vias e células de defesa tornam o paciente hepatopata mais propenso ao desenvolvimento de infecções que influem em sua qualidade de vida e podem piorar o seu prognóstico. Ainda neste grupo, a existência de compostos tóxicos não excretados pelo fígado cirrótico pode favorecer quadros inflamatórios e a latência viral. A família dos Herpesvírus humanos (HHV) possui o atributo de desenvolver latência vitalícia nos indivíduos infectados e seus episódios de reativação podem ser precipitados por quadros de imunossupressão. O uso da saliva para identificação de HHV é viável e pode demonstrar os 8 subtipos virais em diferentes níveis. O objetivo deste estudo foi identificar a presença de HHV-1, HHV-2, VZV, EBV, CMV, HHV-6A, HHV-6B, HHV-7 e HHV-8 em amostras de plasma sanguíneo e saliva de pacientes com cirrose hepática em fila de espera pelo transplante e verificar se a presença desses vírus tem relação com dados da cirrose, como doença descompensada, complicações e etiologia, além de dados advindos de exames sanguíneos, como a população de leucócitos circulantes. Foi desenvolvido um estudo transversal observacional com dados demográficos e médicos de prontuários e amostras de sangue e saliva de 72 indivíduos cirróticos provindas do Biobanco da Faculdade de Odontologia da Universidade de São Paulo, onde permaneceram congeladas em ultrafreezer até o momento da técnica da detecção da cadeia de polimerase. Foram utilizados dois protocolos distintos, o primeiro denominado HSV-Pan, que amplifica o DNA de HHV-1, HHV-2, EBV, CMV e HHV-8, e o segundo denominado VZV-Pan responsável pela amplificação de VZV, HHV-6 tipo A e B e HHV-7. Para as amostras positivas realizou-se subsequente digestão enzimática para identificação do subtipo de HHV. A amostra foi composta majoritariamente por indivíduos do sexo masculino (n=51, 70%), com média de idade 54 anos (DP=10). A mediana do índice MELD foi 15 (DP=6) e 59% foram classificados com cirrose descompensada. 47,2% (n=34) apresentavam leucopenia. Não foram identificados HHV em amostras sanguíneas. Em saliva, os principais HHV identificados foram HHV-7 (n=42, 62%) e EBV (n=30, 41%). Houve correlação estatística entre a presença de HSV-Pan e a identificação de alterações em série branca sanguínea (p=0,019), especificamente com a população total de leucócitos (p=0,025), mas não houve correlação com subpopulações como neutrófilos e linfócitos. Essa correlação aconteceu, provavelmente, às expensas do EBV presente na saliva, já que apenas 5 pacientes apresentaram positividade para outros vírus. De fato, a correlação entre o EBV com leucócitos totais e com linfócitos apresentou-se estatisticamente significante (p=0,038 e p=0,047, respectivamente). Não houve correlação entre a presença viral e outras variáveis independentes, como complicações da cirrose ou doença descompensada. Conclui-se que, na população estudada, a identificação de EBV na saliva está vinculada ao estado de imunidade circulante do paciente cirrótico. É possível que a deficiência imune apresentada pelos pacientes com cirrose possa ter um papel no shedding do EBV em saliva.

Effects of herbal cake separated moxibustion on Tim-4 and ubiquitination of PD-1 in rabbits with immunosuppression / 中国针灸

OBJECTIVE@#To observe the effects of herbal cake separated moxibustion on macrophage effector molecule T-cell immunoglobulin and mucin-domain containing-4 (Tim-4) and ubiquitination of programmed cell death protein 1 (PD-1) in rabbits with immunosuppression, and to explore the possible mechanism on herbal cake separated moxibustion in improving immunosuppression.@*METHODS@#Thirty-two big-ear white rabbits were randomly divided into a normal group, a model group, a moxa stick moxibustion group and a herbal cake separated moxibustion group, 8 rabbits in each group. Except the normal group, the immunosuppression model was established by intraperitoneal injection of cyclophosphamide of60 mg/kg in the other 3 groups. "Shenque" (CV 8), "Shenshu" (BL 23), "Zusanli" (ST 36), etc. were selected in both the moxa stick moxibustion group and the herbal cake separated moxibustion group. Moxa stick moxibustion was applied in the moxa stick moxibustion group, one cone at each acupoint; herbal cake separated moxibustion was applied in the herbal cake separated moxibustion group, 5 cones at each acupoint. The intervention was given once every other day for 10 times in both groups. Leukocyte content in peripheral blood was detected by blood cell analyzer; the positive expression of PD-1 in CD+4 T lymphocytes, CD+8T lymphocytes and CD+68 macrophages in peripheral blood was measured by flow cytometry, the serum levels of interleukin 2 (IL-2), CD8, CD68 and Tim-4 were detected by ELISA, and the expression of Tim-4 and F-box only protein 38 (FBXO38) in the liver and spleen tissues was measured by immunohistochemistry.@*RESULTS@#Compared with the normal group, in the model group, white blood cell count (WBC) and percentage of neutrophils (NEU%) were decreased while percentage of lymphocyte (LYM%) was increased (P<0.01) in peripheral blood; the positive expression rates of PD-1 in CD+4 T lymphocytes, CD+8T lymphocytes and CD+68 macrophages in peripheral blood were increased (P<0.01); the serum levels of IL-2, CD68 and Tim-4 were increased (P<0.01), the serum level of CD8 was decreased (P<0.01); the average optical density (AOD) of Tim-4 in the liver tissue and FBXO38 in the liver and spleen tissues was increased (P<0.01). Compared with the model group, in the moxa stick moxibustion group and the herbal cake separated moxibustion group, WBC and NEU% were increased (P<0.01); the positive expression rates of PD-1 in CD+4 T lymphocytes, CD+8T lymphocytes and CD+68 macrophages in peripheral blood were decreased (P<0.01); the serum levels of IL-2, CD68 and Tim-4 were decreased (P<0.01), the serum levels of CD8 were increased (P<0.01); the AOD of Tim-4 and FBXO38 in the liver tissue and FBXO38 in the spleen tissue was decreased (P<0.01, P<0.05). Compared with the moxa stick moxibustion group, in the herbal cake separated moxibustion group, the positive expression rate of PD-1 in CD+68 macrophages in peripheral blood was increased (P<0.05); serum level of Tim-4 was increased (P<0.01); AOD of Tim-4 in the liver tissue was decreased (P<0.05).@*CONCLUSION@#Herbal cake separated moxibustion can improve immunosuppression by regulating the expression of macrophage effector molecule Tim-4 and the FBXO38 mediated ubiquitination of PD-1, Tim-4 may be one of the specific indexes of immunomodulation involving with herbal cake separated moxibustion.

Research Progress of Regulatory T Cells in the Pathogenesis of Multiple Myeloma --Review / 中国实验血液学杂志

The multiple myeloma (MM), the second most common hematologic malignancy, is malignant proliferative disease of plasma cells. Although the application of many targeted drugs has significantly prolonged the survival time of MM patients, it is still an incurable disease. In recent years, the immunosuppression caused by interaction between tumor microenvironment(TME) and tumor cells has attracted people's attention gradually. As a kind of immunosuppressive cells in TME, regulatory T cells (Treg) play an important role in the progress of MM. Treg is related to the proliferation and metastasis of tumors, and can lead to the progress of MM by promoting the angiogenesis and generating immunosuppressive TME. In this review, we briefly summarized the latest research progress on the impact of Treg on the pathogenesis of MM.

Effect of Eltrombopag on Response to Immunosuppressive Therapy in Patients with Transfusion-Dependent Non-Severe Aplastic Anemia / 中国实验血液学杂志

OBJECTIVE@#To compare the efficacy of eltrombopag combined with cyclosporine A (CsA) and CsA alone in patients with transfusion-dependent non-severe aplastic anemia (TD-NSAA).@*METHODS@#The clinical data of 76 patients with treatment-naive TD-NSAA in Ningde Municipal Hospital of Ningde Normal University and Affiliated Hospital of Nantong University from December 2017 to June 2021 were retrospectively analyzed. Among them, 45 cases were treated with eltrombopag combined with CsA, and 31 patients with compatible baseline characters were treated with CsA alone. The efficacy of patients between the two groups was compared, and the factors affecting the curative effects were also analyzed.@*RESULTS@#There were significant differences in hematological response (HR) and complete response(CR) rates between the two groups at 3, 6, 12 months, and follow-up endpoint of treatment (P<0.05). With the prolongation of eltrombopag treatment time, the curative effect increased gradually, and the patients achieved more CR and HR rates by the end of the follow-up period. Simultaneously, with the increase in the maximum stable dose of eltrombopag, the HR rate increased gradually. The megakaryocyte count in eltrombopag group was higher than that in control at 6 and 12 months (P<0.05). Compared with the control group, the median time of platelet transfusion independence in eltrombopag group was more shorter (P=0.018), and the median platelets transfusion volume was lower (P=0.009). At 3, 6, 12 months after eltrombopag, the change of platelet in eltrombopag group was higher than that in the control group (P<0.05). Analysis of related factors affecting the efficacy showed that sex, age, iron overload, platelet count before treatment had no effect on the efficacy, and the median maximum stable dosage and the administration period for eltrombopag were related to the curative effect. The patients of eltrombopag group experienced adverse events of varying degrees, but the reactions were mild and mostly tolerated.@*CONCLUSION@#Eltrombopag can effectively improve the hematopoietic response and promote platelet recovery for TD-NSAA patients with relatively more residual hematopoietic cells, and it is safe and well tolerated.

Fatores associados à adesão a terapia imunossupressora em indivíduos transplantados renais / Factors associated with adherence to immunosuppressive therapy in renal transplant recipients / Factores asociados a la adherencia a la terapia inmunosupresora en receptores de trasplante renal

Objetivo: Analisar os fatores associados à adesão a terapia imunossupressora em indivíduos transplantados renais. Métodos: Trata-se de estudo de corte transversal, com indivíduos transplantados renais em acompanhamento ambulatorial, na cidade do Recife, Nordeste do Brasil. Utilizou-se a Assessment of Adherence with Immunosuppressive Medication Scale para avaliar a adesão aos imunossupressores. Resultados: Em 147 transplantados renais, foi observada uma prevalência de mulheres (51,70%) com baixa escolaridade e baixo nível socioeconômico (60,54%). A amostra foi composta, em sua maioria, por receptores de enxerto renal proveniente de doador cadáver (50,34%), com tempo de espera para o transplante de até 48 meses (62,59%). A taxa de adesão dos participantes foi de 56,42%, e esteve associada ao tempo médio pós-transplante (p=0,033), com maior índice naqueles com menos de 5 anos de transplante renal. Os fatores associados a não adesão foram atrasos e esquecimentos. Conclusão: Considerando a necessidade de ampliar a taxa de adesão, é fundamental considerar o tempo de transplante renal no planejamento das ações. Além disso, é preciso utilizar estratégias que auxiliem na manutenção da tomada dos imunossupressores conforme prescrição médica a fim de contribuir para a manutenção do enxerto renal. (AU)

Objective: To analyze the factors associated with adherence to immunosuppressive therapy in kidney transplant patients. Methods: This is a cross-sectional study, with kidney transplant patients undergoing outpatient follow-up, in the city of Recife, Northeast Brazil. The Assessment of Adherence with Immunosuppressive Medication Scale was used to assess adherence to immunosuppressants. Results: In 147 kidney transplant recipients, there was a prevalence of women (51,70%), with low education and low socioeconomic status (60,54%). The sample consisted, mostly, of kidney graft recipients from cadaver donors (50,34%), with a waiting time for transplantation of up to 48 months (62,59%). The adherence rate of the participants was 56.42%, and was associated with the average post-transplant time (p = 0.033), with a higher rate in those with less than 5 years of kidney transplantation. The factors associated with non-adherence were delays and forgetfulness. Conclusion: Considering the need to increase the adherence rate, it is essential to consider the time of kidney transplantation when planning actions. In addition, it is necessary to use strategies that assist in maintaining the intake of immunosuppressants according to medical prescription in order to contribute to the maintenance of the renal graft. (AU)

Objetivo: Analizar los factores asociados a la adherencia a la terapia inmunosupresora en receptores de trasplante renal. Métodos: Se trata de un estudio transversal con pacientes con trasplante renal en seguimiento ambulatorio, en la ciudad de Recife, noreste de Brasil. Se utilizó la Assessment of Adherence with Immunosuppressive Medication Scale para evaluar la adherencia a los inmunosupresores. Resultados: En 147 receptores de trasplante renal, hubo una prevalencia de mujeres (51,70%), con bajo nivel educativo y nivel socioeconómico bajo (60,54%). La muestra estuvo compuesta, mayoritariamente, por receptores de injerto renal de donante cadáver (50,34%), con un tiempo de espera para el trasplante de hasta 48 meses (62,59%). La tasa de adherencia de los participantes fue del 56,42% y se asoció con el tiempo medio pos trasplante (p = 0,033), con una tasa mayor en aquellos con menos de 5 años de trasplante renal. Los factores asociados a la no adherencia fueron los retrasos y el olvido. Conclusión: Considerando la necesidad de incrementar la tasa de adherencia, es fundamental considerar el momento del trasplante renal a la hora de planificar acciones. Además, es necesario utilizar estrategias que ayuden a mantener la ingesta de inmunosupresores según prescripción médica para contribuir al mantenimiento del injerto renal. (AU)

Direct costs associated with lupus nephritis management in the Private Healthcare System in Brazil: an expert panel perspective / Custos diretos associados ao manejo da nefrite lúpica no Sistema de Saúde Privado no Brasil: uma perspectiva segundo painel de especialistas

Objective: To estimate direct medical costs of lupus nephritis (LN) in the Brazilian private healthcare system. Methods: An expert panel of five specialists were convened to discuss health resource usage in LN patient management. The discussion included diagnosis, treatment, and disease monitoring, including dialysis and kidney transplantation. Unit costs (in BRL) were obtained from public sources, and an estimation of 1-year costs was conducted. Results: Approximately 76.0% of patients with LN undergo kidney biopsy, of which 48.1% present with LN classes III­IV and 21.4% have class V. Around 67.5% of patients with LN classes III­IV experience an average of four renal flares annually. Overall, 20.3% of patients present refractory LN, and 10.3% have end-stage kidney disease (ESKD), requiring dialysis and kidney transplantation. Estimated total weighted annual costs per patient were BRL 115,824.81 for LN classes III­IV, BRL 85,684.79 for LN class V, BRL 115,594.98 for refractory LN; and BRL 325,712.88 for ESKD. The main annual cost driver for LN classes III­IV was renal flares (BRL 60,240.41; 52.0%) and dialysis for LN class V (BRL 31,128.38; 36.3%). Conclusions: Total direct costs increase when LN progresses to ESKD. Although it is challenging to improve the diagnosis, identification of the disease at an early stage, together with rapid initiation of treatment, are fundamental elements to optimize results, potentially reducing costs to the system and the impact of disease burden and quality of life on patients.

Objetivo: Estimar os custos médicos diretos da nefrite lúpica (NL) no sistema suplementar de saúde brasileiro. Métodos: Um painel de cinco especialistas foi estruturado para discutir o uso de recursos em saúde no manejo de pacientes com NL. Nesta discussão, incluíram-se o diagnóstico, o tratamento e o monitoramento da doença, contemplando também diálise e transplante renal. Os custos unitários foram obtidos de fontes públicas e os resultados expressos em custo anual. Resultados: Aproximadamente 76,0% dos pacientes com NL são submetidos à biópsia renal, sendo 48,1% com NL de classes III-IV e 21,4% de classe V. Cerca de 67,5% dos pacientes com classes III-IV apresentam, aproximadamente, quatro flares renais anuais. No geral, 20,3% dos pacientes apresentam NL refratária e 10,3% desenvolvem doença renal terminal (DRT), necessitando de diálise e transplante renal. O custo ponderado anual estimado por paciente foi de R$ 115.824,81 para NL de classes III-IV, R$ 85.684,79 para classe V, R$ 115.594,98 para NL refratária e R$ 325.712,88 para DRT. O principal fator para incremento dos custos anuais para NL de classes III-IV foram os flares renais (R$ 60.240,41; 52,0%) e, na classe V, a diálise (R$ 31.128,38; 36,3%). Conclusões: Há um incremento dos custos diretos da NL na progressão para DRT. Embora seja desafiador melhorar o diagnóstico, a identificação da doença em uma fase precoce, aliada ao tratamento iniciado de forma célere, são elementos fundamentais para otimizar os resultados, potencialmente reduzindo os custos ao sistema e o impacto da carga da doença e qualidade de vida dos pacientes.

Reactivación de la enfermedad de Chagas después de trasplante autólogo de progenitores hematopoyéticos. Reporte de caso y revisión de la literatura / Chagas disease reactivation after autologous stem cell transplant. Case report and literature review

Introducción. La enfermedad de Chagas es una parasitosis endémica en Latinoamérica transmitida por triatominos. Está asociada a factores de riesgo como la pobreza y la ruralidad. Después de la infección aguda, un tercio de los pacientes presenta compromiso del corazón, el aparato digestivo o el sistema nervioso central, en tanto que los dos tercios restantes no presentan este tipo de compromiso secundario. La inmunosupresión farmacológica rompe el equilibrio entre el sistema inmunitario y el parásito, lo cual favorece su reactivación. Caso clínico. Se presenta el caso de un hombre de 58 años procedente de un área rural colombiana, con diagnóstico de mieloma múltiple resistente a los fármacos de primera línea de tratamiento, que requirió un nuevo esquema de quimioterapia y consolidación con trasplante autólogo de células madre. Después del trasplante, presentó neutropenia febril. Los estudios microbiológicos iniciales fueron negativos. En el frotis de sangre periférica, se demostraron tripomastigotes y se diagnosticó enfermedad de Chagas aguda posterior al trasplante. Se inició el tratamiento con benznidazol. La evolución del paciente fue satisfactoria. Conclusiones. La serología positiva para Chagas previa a un trasplante obliga a descartar la reactivación de la enfermedad en caso de neutropenia febril. Se requieren más estudios para determinar las herramientas que permitan estimar la probabilidad de reactivación de la enfermedad y decidir sobre la mejor opción de relación entre costo, riesgo y beneficio de la terapia profiláctica.

Introduction: Chagas disease is an endemic parasitic infection in Latin America transmitted by triatomines. It is associated with risk factors such as poverty and rurality. After acute infection, a third of patients will present target organ involvement (heart, digestive tract, central nervous system). The remaining two thirds remain asymptomatic throughout their life. Pharmacological immunosuppression breaks the balance between the immune system and the parasite, favoring its reactivation. Clinical case: We present the case of a 58-year-old man from a Colombian rural area with a diagnosis of multiple myeloma refractory to the first line of treatment who required a new chemotherapy scheme and consolidation with autologous stem cell transplant. During the post-transplant period, he suffered from febrile neutropenia. Initial microbiological studies were negative but the peripheral blood smear evidenced trypomastigotes in blood. With a diagnosis of acute Chagas disease in a post-transplant patient, benznidazole was started. The evolution of the patient was satisfactory. Conclusions: Positive serology prior to transplantation makes it necessary to rule out reactivation of the pathology in the setting of febrile neutropenia. More studies are required to determine tools for estimating the probability of reactivation of the disease and defining the best cost-risk-benefit relation for the prophylactic therapy.

Manifestaciones mucocutáneas y su relación con el recuento de linfocitos T CD4 en pacientes infectados con el virus de inmunodeficiencia humana hospitalizados en Medellín, Colombia / Mucocutaneous manifestations and their relationship with CD4 T-lymphocyte count in hospitalized patients infected with the human immunodeficiency virus (HIV) in Medellín, Colombia

Introducción. Entre el 80 y el 95 % de los pacientes infectados por el virus de inmunodeficiencia humana (HIV) desarrollan manifestaciones en la piel que sirven como marcadores de su estado inmunológico. Objetivos. Describir las manifestaciones dermatológicas y los factores clínicos y sociodemográficos de los pacientes hospitalizados con diagnóstico de HIV y su correlación con el recuento de linfocitos T CD4. Materiales y métodos. Se hizo un estudio observacional de corte transversal y retrospectivo a partir del registro de las historias clínicas de 227 pacientes mayores de edad con diagnóstico de HIV, evaluados por dermatología en un hospital de Medellín, Colombia. Resultados. Los 227 registros daban cuenta de 433 manifestaciones dermatológicas, el 64,4 % de ellas infecciosas. Las tres manifestaciones más frecuentes fueron candidiasis oral, condilomas acuminados y reacciones a medicamentos. Se encontró una relación estadísticamente significativa entre el virus del herpes zóster (HZ) diseminado y la sífilis secundaria, con un recuento de CD4 entre 200 y 499 células/mm3 (p=0,04 y 0,028, respectivamente), y entre la candidiasis oral y un recuento de CD4 menor de 100 células/ mm3 (p=0,008). Conclusiones. La relación entre el herpes zóster diseminado y un recuento de CD4 entre 200 y 499 células/mm3 sugiere que, a pesar de los recuentos altos, se pueden presentar formas graves de la enfermedad debido a una posible disfunción de las células T y el agotamiento del sistema inmunológico. La relación entre la candidiasis oral y un recuento de CD4 menor de 100 células/mm3 plantea la posibilidad de considerar esta infección micótica como un marcador importante de debilitamiento inmunológico de los pacientes con HIV.

Introduction. About 80-95% of patients infected with the human immunodeficiency virus (HIV) develop skin manifestations, which are markers of the patients' immune status. Objective. To describe the dermatologic manifestations and the clinical and sociodemographic factors of hospitalized patients diagnosed with HIV and their correlation with CD4 T-lymphocyte count. Materials and methods. We conducted an observational, cross-sectional, and retrospective study of the medical records of 227 adult patients with HIV diagnosis evaluated by dermatology in a hospital in Medellín, Colombia. Results. We included 227 patient records with 433 dermatologic manifestations, 64.4% of them infectious. The most frequent manifestations were oral candidiasis, condylomata acuminata, and drug reactions. Moreover, a statistically significant relationship was found between disseminated herpes zoster virus and secondary syphilis with a CD4 count between 200-499 cells/mm3 (p=0.04 and 0.028, respectively). There was also a statistically significant relationship between oral candidiasis and a CD4 count of less than 100 cells/ mm3 (p=0.008). Conclusions. The relationship between disseminated herpes zoster with CD4 between 200-499 cells/mm3 suggests that, despite having high CD4 counts, severe forms of the disease may occur due to possible T-cell dysfunction and depletion of the immune system. Additionally, the relationship between oral candidiasis and CD4 less than 100 cells/mm3 indicates the potential role of oral candidiasis as an essential marker of weakened immune status in HIV patients.

Reactivación de brucelosis en paciente receptor de trasplante hematopoyético autólogo: reporte de caso / Reactivation of brucellosis in an autologous hematopoietic transplant recipient: a case report

Introducción: La brucelosis es la zoonosis más frecuente, producida por el género brucella, que afecta a varias especies de mamíferos y dentro de ellos a los humanos. Se transmite al hombre por contacto directo con los animales infectados, por sus excretas o por la ingestión de productos no pasteurizados. En los últimos años se ha descrito un incremento de la enfermedad en los pacientes inmunocomprometidos. Objetivo: Describir la reactivación de la brucelosis en paciente receptor de un trasplante hematopoyético, su curso y manejo. Presentación de caso: Se presenta una paciente con linfoma de Hodgkin y antecedentes de brucelosis que recibió un trasplante hematopoyético autólogo mieloablativo. Después de la recuperación hematológica, inició con cuadro de fiebre, diaforesis, dolores articulares y hepato-esplenomegalia. Se le diagnosticó brucelosis, por lo que se inició tratamiento con doxiciclina y rifampicina, con lo que se logró la eliminación de los síntomas y la negativización de las pruebas evolutivas. Conclusiones: La brucelosis puede mantenerse meses o años asintomática y reactivarse después de la inmunosupresión en los pacientes trasplantados. Su sospecha y rápido tratamiento puede lograr la curación y evitar complicaciones(AU)

Introduction: Brucellosis is the most frequent zoonosis, produced by the genus brucella, which affects several species of mammals, including human beings. It is transmitted to persons by direct contact with infected animals, by their excreta or by ingestion of unpasteurized products. In recent years, an increase has been described in immunocompromised patients. Objectives: To describe the reactivation of brucellosis in a hematopoietic transplant recipient patient, its course and management. Case presentation: A patient with Hodgkin's lymphoma and a history of brucellosis is presented; that she received a myeloablative autologous hematopoietic transplant. After haematological recovery, she started with symptoms of fever, diaphoresis, joint pain and hepato-splenomegaly. She was diagnosed with brucellosis, so treatment with doxycycline and rifampin was started, which eliminated the symptoms and made the evolutionary tests negative. Conclusions: Brucellosis can be asymptomatic for months or years and after immunosuppression it can be reactivated in transplanted patients. Suspicion and prompt treatment can bring about a cure and avoid complications(AU)

Vasculitis reumatoidea como manifestación extraarticular en dos casos / Rheumatoid vasculitis as an extra articular manifestation in two cases

La vasculitis reumatoidea es un proceso inflamatorio poco frecuente que confiere una morbilidad y mortalidad significativa en pacientes con artritis reumatoidea (AR). Presenta una incidencia de 0,7 a 5,4% de los casos de AR y hasta un 40% de mortalidad a 5 años, siendo la manifestación extraarticular de mayor gravedad1,2. Se caracteriza por el desarrollo de vasculitis necrotizante; ocurre típicamente en pacientes masculinos con AR seropositiva de larga data, nodular y erosiva, tabaquistas y, en general, tiene mal pronóstico. Se presenta una serie de casos, paciente masculino y femenino con AR y manifestaciones extraarticulares, necrosis digital y compromiso multiorgánico, interpretados como cuadros de vasculitis reumatoidea, realizando tratamiento de referencia con inmunosupresores.

Rheumatoid vasculitis is a rare inflammatory process that confers significant morbidity and mortality in patients with rheumatoid arthritis (RA); it has an incidence of 0.7 to 5.4% of RA cases and up to 40% mortality at five years, making it the most serious of all the extra-articular manifestations of RA1,2. It is characterized by the development of necrotizing vasculitis, it typically occurs in male patients with long-standing seropositive RA, erosive nodular, smokers and generally has a poor prognosis. A series of cases is presented, male and female with RA and extra-articular manifestations, digital necrosis and multiorgan system involvement, interpreted as rheumatoid vasculitis, undergoing treatment with immunosuppressants.

Modeling of covariates predicting renal allograft failure within six months after transplantation / Modelagem das covariáveis preditivas para falência do enxerto renal até seis meses do transplante

INTRODUCTION: Kidney transplantation (KT) is the renal replacement therapy (RRT) of choice for patients with chronic kidney disease (CKD). However, not every KT is successful and some patients persist on RRT. OBJECTIVE: To model a logistic regression with pre- and post-KT risk covariates capable of predicting secondary allograft dysfunction in need of RRT or reaching stage V of CKD until the first six months post-KT. METHODS: Cohort with KT recipients from Northeastern Brazil. Medical records of KT performed between 2011-2018 were analyzed. KT-recipients with insufficient data or who abandoned follow-up were excluded. The covariables analyzed were: demographic; infectious; pre- and post-KT comorbidities; panel reactive-antibodies; number of HLA mismatches; acute rejection episodes mediated by T-cell (ACR) or antibodies (AAR) six months after KT; and laboratory tests six months after KT. RESULTS: Covariates with higher risk for the analyzed outcomes six months after KT were: elderly KT recipients (OR:1.41; CI95%:1.01-1.99), time between onset of RRT and KT (ΔT-RRT&KT)>10years (OR:3.54; CI95%:1.27-9.87), diabetes mellitus (DM) pre-KT (OR:3.35; CI95%:1.51-7.46), pyelonephritis (OR:2.45; CI95%:1.24-4.84), polyomavirus nephropathy (OR:4.99; CI95%:1.87-13.3), AAS (OR:4.82; CI95%:1.35-17.2), 24h-proteinuria ≥300mg/24h (OR:5.05; CI95%:2.00-12.7) and serum calcium (Ca) <8.5mg/dL (OR:4.72; CI95%:2.00-11.1). The multivariate model presented an accuracy of 88.1% and the mean variance inflation factor is 1.81. CONCLUSION: Elderly-recipients, ΔT-RRT&KT>10 years, pre-KT DM, and post-KT aggressions until six months (pyelonephritis, polyomavirus nephropathy, ABMR, 24h-proteinuria≥300mg/24h, and Ca<8.5mg/dL) are associated with high predictive power for secondary allograft dysfunction in need of RRT or reaching CKD stage V until the first six months post-KT.

INTRODUÇÃO: Transplante renal (TR) é a terapia renal substitutiva (TRS) de escolha para pacientes com doença renal crônica (DRC). Entretanto, nem todo TR é bem-sucedido e alguns pacientes persistem em TRS. OBJETIVO: Modelar uma regressão logística com covariáveis de risco pré e pós-TR preditora da disfunção secundária do aloenxerto com necessidade de TRS ou alcance ao estágio V da DRC até os primeiros seis meses pós-TR. MÉTODOS: Coorte com receptores transplantados realizado em hospital no Nordeste brasileiro. Analisou-se registros médicos dos TR realizados entre 2011-2018. Receptores com dados insuficientes ou que abandonaram seguimento foram excluídos. Foram analisadas covariáveis: demográficas; infecciosas; comorbidades pré e pós-TR; painel de reatividade; incompatibilidades de HLA; episódios de rejeições agudas mediadas por células-T ou por anticorpos; exames laboratoriais seis meses pós-TR. RESULTADOS: Receptores idosos (OR:1,41; IC95%:1,01-1,99), tempo entre início da TRS e TR (∆T-TRS&TR)>10 anos (OR:3,54; IC95%:1,27-9,87), diabetes mellitus (DM) pré-TR (OR:3,35; IC95%:1,51-7,46), pielonefrite (OR:2,45; IC95%:1,24-4,84), nefropatia por poliomavírus (OR:4,99; IC95%:1,87-13,3), RAMA (OR:4,82; IC95%:1,35-17,2), proteinúria de 24h (Pt24h) ≥300mg/24h (OR:5,05; IC95%:2,00-12,7) e cálcio sérico (Ca)<8,5mg/dL (OR:4,72; IC95%:2,00-11,1) foram identificadas como covariáveis de maior risco para os desfechos analisados até seis meses pós-TR. O modelo multivariado apresentou acurácia de 88,1% e fator de inflação da variância médio de 1,81. CONCLUSÃO: Receptores idosos, ∆T-TRS&TR>10anos, DM pré-TR e agressões até seis meses pós-TR (pielonefrite, nefropatia por poliomavírus, RAMA, Pt24h≥300mg/24h e Ca<8,5mg/dL), apresentam alto poder preditivo para disfunção secundária do aloenxerto com necessidade de TRS ou alcance ao estágio V da DRC até os primeiros seis meses pós-TR.

Sarcoma de Kaposi en diagnóstico tardío de VIH/sida / Kaposi sarcoma in late HIV/AIDS diagnosis

Introducción: El sarcoma de Kaposi es una neoplasia maligna multifocal de células endoteliales, que se presenta con lesiones características en la piel, boca y ganglios linfáticos. Objetivo: Describir un caso de sarcoma de Kaposi que, por sus características, entorpeció el diagnóstico de infección por VIH. Presentación del caso: Paciente masculino, de 30 años, diagnosticado recientemente con síndrome de inmunodeficiencia adquirida, sin tratamiento. Fue referido a la consulta de cirugía maxilofacial para biopsia de adenopatía cervical derecha. Durante el examen físico se observó edema generalizado en ambos miembros inferiores, con lesiones hiperpigmentadas de aspecto macular y papular de varias tonalidades. En la mucosa del paladar duro se apreció una lesión pigmentada violácea, que abarcaba la línea media palatina y se extendía hacia la hemiarcada izquierda. Se realizó la exégesis de la adenopatía con fines diagnósticos, con lo cual se confirmó sarcoma de Kaposi. Conclusiones: La falta de familiaridad con las características clínicas, así como la falta de una biopsia de las lesiones cutánea y un examen completo de la cavidad oral, ocasionaron que esta neoplasia pasara desapercibida en los exámenes médicos de rutina en el caso presentado, lo que condujo a un bajo índice de sospecha de la infección por VIH/sida y retrasó el tratamiento oportuno. Cuando la inmunosupresión está avanzada, el sarcoma de Kaposi relacionado al síndrome de inmunodeficiencia adquirida tiende a ser más agresivo(AU)

Introduction: Kaposi sarcoma is a multifocal malignant neoplasm of endothelial cells which presents with characteristic lesions on the skin, mouth and lymph glands. Objective: Describe a case of Kaposi sarcoma with characteristics that hindered HIV infection diagnosis. Case presentation: A case is presented of a male 30-year-old patient recently diagnosed with acquired immunodeficiency syndrome, and not following any treatment. The patient was referred to the maxillofacial surgery service for right cervical adenopathy biopsy. Physical examination revealed generalized edema in both lower limbs, with hyperpigmented lesions of macular and papular appearance and various shades of color. A purplish pigmented lesion was detected in the hard palate mucosa. The lesion covered the palatal midline and extended toward the left hemiarch. Exeresis of the adenopathy was performed for diagnostic purposes, confirming the diagnosis of Kaposi sarcoma. Conclusions: Lack of familiarity with the clinical characteristics of Kaposi sarcoma, and not performing a biopsy of the skin lesions and a complete examination of the oral cavity, made the neoplasm go unnoticed to routine medical tests, leading to low suspicion of HIV/AIDS infection and delaying timely treatment. In advanced immunosuppression, Kaposi sarcoma related to acquired immunodeficiency syndrome tends to be more aggressive(AU)

Mucormicosis orbitorrinocerebral: el manejo más allá de la cirugía. Informe de caso clínico y revisión de la literatura / Rhino-orbital-cerebral mucormycosis: management beyond surgery. Clinical case report and literature review

Introducción: se presenta el caso clínico de un paciente con mucormicosis orbitorrinocerebral y revisión de la literatura. Caso clínico: se trata de hombre de 45 años que consultó por síntomas nasosinusales manejado ambulatoriamente con múltiples antibióticos sin mejoría, por lo cual se realizó manejo quirúrgico con toma de muestras que revelaron hifas compatibles con mucormicosis. Cuando acudió a la institución presentaba extensión de la infección a todas las cavidades nasales y parte de la base del cráneo. En la búsqueda de la inmunosupresión, se encontró una diabetes de novo de difícil control. Discusión: la mucormicosis orbitorrinocerebral es una enfermedad altamente invasiva que requiere un manejo multidisciplinario, cirugías seriadas y extendidas, antimicóticos tópicos y sistémicos. El pronóstico mejora y la evolución puede ser favorable cuando se logra controlar la causa de la inmunosupresión, en este caso la diabetes. Conclusiones: es requisito fundamental realizar un tratamiento multidisciplinario en el abordaje de estos pacientes, tanto en la especialidad clínica como en la quirúrgica, psicosocial, nutricional y de rehabilitación.

Introduction: It is the clinical case of a patient with rhino-orbital-cerebral mucormycosis and the review of the literature. Clinical case: We present the case of a previously healthy young man who started with sinonasal symptoms and hyphae compatible with mucormycosis were found in the initial samples of outpatient care. When he came to the institution, the infection had spread to all the nasal cavities and part of the skull base. Discussion: Searching for baseline immunosuppression, only difficult-to-control diabetes and de novo diagnosis were found. It required multidisciplinary management, serial and extended surgeries, topical, venous and oral antifungals. The prognosis improved and the evolution became favorable when glycemic control was achieved. Conclusion: It is a fundamental requirement to carry out a multidisciplinary work for the approach to these patients, both in the clinical, surgical, psychosocial, nutritional and rehabilitation specialties.

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.

Adherence to Immunosuppressive Medications in Kidney Transplant Patients at Three Centers in Khartoum State, Sudan: A Cross-sectional Hospital Study

Background: Graft survival post-kidney transplantation is of paramount importance to patients and nephrologists. Nonadherence to immunosuppressive therapy can be associated with deterioration of renal function and graft rejection. This study aimed to evaluate the adherence to immunosuppressive medications in kidney transplant patients at three centers in Khartoum, Sudan. Methods: In this descriptive cross-sectional hospital-based survey, 277 post-kidneytransplant patients were recruited. Data were collected using a questionnaire and analyzed using the SPSS v.23. Our scoring method was calculated based on Morisky Medication Adherence Scale (MMAS-8) related to immunosuppressive medications and was expressed as questions in the questionnaire; every correct answer was given one mark, then the marks were gathered and their summation was expressed. Results: Overall, 33% ,45%, and 22% of the studied participants reported high, medium, and low adherence, respectively. The major factor for nonadherence was forgetfulness affecting 36.1% of those who did not adhere. The cost of the immunosuppressive medications did not negatively affect any of the participants' adherence (100%). However, a significant association was seen between adherence and occupational status, duration of transplantation, shortage of immunosuppressants, recognizing the name of immunosuppressant, side effect, and forgetfulness (P-values = 0.002, 0.01, 0.006 , 0.000, 0.022, and 0.000, respectively). Logistic regression analysis showed a significant association with occupational status, side effects, and forgetfulness.

Significance of paroxysmal nocturnal hemoglobinuria clone in immunosuppressive therapy for children with severe aplastic anemia / 中国当代儿科杂志

OBJECTIVES@#To study the association between paroxysmal nocturnal hemoglobinuria (PNH) clone and immunosuppressive therapy (IST) in children with severe aplastic anemia (SAA).@*METHODS@#A retrospective analysis was performed on the medical data of 151 children with SAA who were admitted and received IST from January 2012 to May 2020. According to the status of PNH clone, these children were divided into a negative PNH clone group (n=135) and a positive PNH clone group (n=16). Propensity score matching was used to balance the confounding factors, and the impact of PNH clone on the therapeutic effect of IST was analyzed.@*RESULTS@#The children with positive PNH clone accounted for 10.6% (16/151), and the median granulocyte clone size was 1.8%. The children with positive PNH clone had an older age and a higher reticulocyte count at diagnosis (P<0.05). After propensity score matching, there were no significant differences in baseline features between the negative PNH clone and positive PNH clone groups (P>0.05). The positive PNH clone group had a significantly lower overall response rate than the negative PNH clone group at 6, 12, and 24 months after IST (P<0.05). The evolution of PNH clone was heterogeneous after IST, and the children with PNH clone showed an increase in the 3-year cumulative incidence rate of aplastic anemia-PNH syndrome (P<0.05).@*CONCLUSIONS@#SAA children with positive PNH clone at diagnosis tend to have poor response to IST and are more likely to develop aplastic anemia-PNH syndrome.

Pharmacokinetic study of anti-human T-cell porcine immunoglobulin combined with cyclosporine A immunosuppressive therapy in patients with severe aplastic anemia / 中华血液学杂志

Objective: To study the metabolic characteristics of anti-human T-cell porcine immunoglobulin (p-ATG) in patients with severe aplastic anemia (SAA) . Methods: For patients with SAA treated with p-ATG combined cyclosporine A (CsA) immunosuppressants between February 2017 and December 2017, the p-ATG dose was 20 mg·kg(-1)·d(-1) over 12 h of intravenous administration for 5 consecutive days. The blood concentration of p-ATG was detected by the three-antibody sandwich ELISA method, the pharmacokinetic analysis software was fitted, and the second-chamber model method was used to calculate the pharmacokinetic parameters and plot the pharmacokinetic curve. Adverse events were recorded and the hematologic reactions were determined at 6 months after treatment. Results: Sixteen patients with SAA treated with p-ATG were enrolled, including 8 females and 8 males, with a median age of 22 years (range, 12 to 49 years) and a median weight of 62.5 kg (range, 37.5 to 82.0 kg) . The pharmacokinetics of p-ATG could be evaluated in 14 cases. p-ATG is distributed in vivo as a two-chamber model, with an average drug concentration peak (T(max)) of (5.786±2.486) days, a peak concentration (C(max)) of (616±452) mg/L, and a half-life of (10.479±8.242) days. The area under the drug time curve (AUC) was (5.807±3.236) mg/L·d. Six months after treatment, 8 of 14 patients received a hematologic response; the AUC (0-t) of the effective group and ineffective groups was (7.50±3.26) mg/L·d vs (4.50±2.18) mg/L·d, and the C(max) was (627±476) mg/L vs (584±382) mg/L, respectively. Conclusion: The plasma concentration of p-ATG reached a peak after 5 days of continuous infusion, and then decreased slowly, with a half-life of 10.479 days, and the residual drug concentration was detected in the body 60 days after administration. A relationship between drug metabolism and efficacy and adverse reactions could not be determined.

Reassessing the six months prognosis of patients with severe or very severe aplastic anemia without hematological responses at three months after immunosuppressive therapy / 中华血液学杂志

Objective: To reassess the predictors for response at 6 months in patients with severe or very severe aplastic anemia (SAA/VSAA) who failed to respond to immunosuppressive therapy (IST) at 3 months. Methods: We retrospectively analyzed the clinical data of 173 patients with SAA/VSAA from 2017 to 2018 who received IST and were classified as nonresponders at 3 months. Univariate and multivariate logistic regression analysis were used to evaluate factors that could predict the response at 6 months. Results: Univariate analysis showed that the 3-month hemoglobin (HGB) level (P=0.017) , platelet (PLT) level (P=0.005) , absolute reticulocyte count (ARC) (P<0.001) , trough cyclosporine concentration (CsA-C0) (P=0.042) , soluble transferrin receptor (sTfR) level (P=0.003) , improved value of reticulocyte count (ARC(△)) (P<0.001) , and improved value of soluble transferrin receptor (sTfR(△)) level (P<0.001) were related to the 6-month response. The results of the multivariate analysis showed that the PLT level (P=0.020) and ARC(△) (P<0.001) were independent prognostic factors for response at 6 months. If the ARC(△) was less than 6.9×10(9)/L, the 6-month hematological response rate was low, regardless of the patient's PLT count. Survival analysis showed that both the 3-year overall survival (OS) [ (80.1±3.9) % vs (97.6±2.6) %, P=0.002] and 3-year event-free survival (EFS) [ (31.4±4.5) % vs (86.5±5.3) %, P<0.001] of the nonresponders at 6 months were significantly lower than those of the response group. Conclusion: Residual hematopoietic indicators at 3 months after IST are prognostic parameters. The improved value of the reticulocyte count could reflect whether the bone marrow hematopoiesis is recovering and the degree of recovery. A second treatment could be performed sooner for patients with a very low ARC(△).

Neurotoxoplasmosis con presentación imagenológica atípica / Atypical imaging presentation of neurotoxoplasmosis

La toxoplasmosis cerebral o neurotoxoplasmosis es una de las infecciones por agentes oportunistas más frecuentes en pacientes infectados por virus de inmunodeficiencia humana (VIH) y se relaciona con inmunodeficiencia severa. En estos pacientes causa lesiones neurológicas de alto grado e incluso la muerte. Suele aparecer como múltiples focos de lesión de predominio gangliobasal y con realce anular. Se presenta un caso clínico de neurotoxoplasmosis en paciente VIH con un patrón radiológico poco frecuente.

Cerebral toxoplasmosis or neurotoxoplasmosis is one of the most frequent infections by opportunistic agents in HIV-infected patients and is associated with severe immunodeficiency. In these patients, it causes high-grade neurological lesions and even death. It usually appears as multiple foci of lesions with gangliobasal predominance and annular enhancement. We present a clinical case of neurotoxoplasmosis in a HIV patient with an unusual radiological pattern.