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INTRODUCTION: The global health crisis caused by the COVID-19 pandemic has resulted in severe mortality and morbidity. Immunosuppressed patients, such as kidney transplant recipients, are particularly susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. OBJECTIVE: The aim of this cohort study was to evaluate the impact of COVID-19 vaccination on clinical outcomes in patients with kidney transplants. MATERIALS AND METHODS: In this retrospective study, 254 patients with kidney transplants were vaccinated against SARS-CoV-2 and a fraction of these contracted COVID-19. The diagnosis of COVID-19 was carried out by reverse transcriptase-polymerase chain reaction testing, and the patients received treatment involving immunosuppressive and COVID-19-specific protocols. RESULTS: SARS-CoV-2 infection was diagnosed in 38 (14.96%) patients before the COVID-19 vaccine was administered. After vaccination, an additional 29 (11.42%) patients were diagnosed with COVID-19. Risk factors for hospitalization included age, body mass index (BMI), comorbidities, and time elapsed since renal transplantation (p = 0.025, 0.038, 0.012, and 0.046, respectively). COVID-19 vaccination resulted in a significant decrease in the rate of hospital-acquired SARS-CoV-2 infection from 63.16% to 34.48% (p = 0.020). The proportion of patients from this cohort placed in intensive care units decreased from 23.68% to zero. Allograft rejections exhibited a decreasing trend from 13.16% to 6.90% (p = 0.690). This patient cohort displayed 15.79% mortality prior to COVID-19 vaccination that was reduced to nil after immunization. CONCLUSION: COVID-19 vaccination significantly reduced COVID-19 severity and mortality in this cohort of patients with kidney transplants. The risk factors for hospitalization were determined to be age, BMI, comorbidities, and time since renal transplantation. COVID-19 vaccination resulted in a clinical outcome of reduced hospitalization and a decrease in clinical complications. The COVID-19 vaccination-derived adverse effects in this cohort were found to be comparable to those in the immunocompetent population.

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BACKGROUND: Real-world, primary data on the treatment of psoriasis are scarce, especially concerning the role of soluble biomarkers as outcome predictors. OBJECTIVE: The authors evaluated the utility of Th1/Th17 serum cytokines along with clinical characteristics as predictors of drug survival in the treatment of psoriasis. METHODS: The authors consecutively included participants with moderate to severe psoriasis who were followed up for 6 years. Baseline interferon-α, tumor necrosis factor-α, and interleukin (IL)-2, IL-4, IL-6, IL-10, and IL-17A were measured using a cytometric bead array; clinical data were assessed. The authors calculated hazard ratios (HRs) for drug survival using a Cox proportional hazards model. RESULTS: The authors included 262 patients, most of whom used systemic immunosuppressants or biologics. In the multivariate model, poor quality of life measured by the Dermatology Life Quality Index (HR = 1.04; 95% CI 1.01‒1.07; p = 0.012) and elevated baseline IL-6 (HR = 1.99; 95% CI 1.29‒3.08; p = 0.002) were associated with treatment interruption. STUDY LIMITATIONS: The main limitation of any cohort study is the presence of confounders that could not be detected in clinical evaluation. CONCLUSIONS: Poor quality of life and elevated baseline serum IL-6 level predicted treatment interruption in patients with moderate to severe psoriasis. Although IL-6 is not the most important mediator of the inflammatory pathway in the skin environment, it is an interesting biomarker candidate for predicting psoriasis treatment response.

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Resumo Fundamento É desconhecido se a linfopenia é fator de risco para a reativação da doença de Chagas no transplante cardíaco (TxC), como recentemente descrito na reativação de citomegalovírus em pacientes transplantados. Objetivo Avaliar se a linfopenia no perioperatório do TxC está relacionada à parasitemia precoce pelo Trypanosoma cruzi. Métodos Amostra analisada (janeiro de 2014 a janeiro de 2023) em estudo observacional e retrospectivo. A parasitemia foi avaliada nos primeiros 3 meses após o TxC por meio da reação em cadeia da polimerase sérica (PCR) e comparada com a contagem total de linfócitos no perioperatório do TxC por curvas ROC. Comparadas características de base com a PCR Chagas por modelos de risco proporcionais de Cox independentes. Nível de significância adotado de 5%. Resultados Amostra (n = 35) apresentou idade média de 52,5 ± 8,1 anos e PCR Chagas positiva em 22 pacientes (62,8%). As médias dos menores valores de linfócitos nos primeiros 14 dias do TxC foram 398 ± 189 e 755 ± 303 células/mm3 em pacientes com e sem parasitemia nos 3 meses após o TxC, respectivamente (área sob a curva = 0,857; intervalo de confiança de 95%: 0,996 a 0,718, sensibilidade e especificidade de 83,3% e 86,4%). Determinado valor de corte inferior a 550 linfócitos/mm3 como fator de risco para presença de parasitemia. Pacientes com linfócitos < 550 unidades/mm3 nos primeiros 14 dias do pós-TxC apresentaram PCR positiva em 80% dos casos. Para cada aumento de 100 linfócitos/mm3, o risco de positividade da PCR é reduzido em 26% (razão de riscos = 0,74; intervalo de confiança de 95%: 0,59 a 0,93, p = 0,009). Conclusão Houve associação entre a linfopenia no perioperatório do TxC com a parasitemia precoce pelo T. cruzi detectada por PCR.

Abstract Background It is unknown whether lymphopenia is a risk factor for the reactivation of Chagas disease in heart transplantation (HTx), as recently described in the reactivation of cytomegalovirus in transplant patients. Objective To evaluate whether lymphopenia in the perioperative period of heart transplantation is related to early Trypanosoma cruzi parasitemia. Methods This observational, retrospective study analyzed a sample from January 2014 to January 2023). Parasitemia was evaluated in the first 3 months after HTx using serum polymerase chain reaction (PCR) and compared with the total lymphocyte count in the perioperative period of HTx using receiver operating characteristic curves. Baseline characteristics were compared with PCR for Chagas using independent Cox proportional hazards models. A significance level of 5% was adopted. Results The sample (n = 35) had a mean age of 52.5 ± 8.1 years, and 22 patients (62.8%) had positive PCR for Chagas. The mean lowest lymphocyte values in the first 14 days after HTx were 398 ± 189 and 755 ± 303 cells/mm3 in patients with and without parasitemia, respectively, within 3 months after HTx (area under the curve = 0.857; 95% confidence interval: 0.996 to 0.718, sensitivity and specificity of 83.3% and 86.4%). A cutoff value of less than 550 lymphocytes/mm3 was determined as a risk factor for the presence of parasitemia. Patients with lymphocytes < 550 units/mm3 in the first 14 days after HTx presented positive PCR in 80% of cases. For every increase of 100 lymphocytes/mm3, the risk of PCR positivity was reduced by 26% (hazard rate ratio = 0.74; 95% confidence interval: 0.59 to 0.93, p = 0.009). Conclusion There was an association between lymphopenia in the perioperative period of HTx and early T. cruzi parasitemia detected by PCR.

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BACKGROUND: Acute rejection remains one of the main complications in the first months after transplantation and may influence long-term outcomes. Tacrolimus has proven its usefulness in solid organ transplants and its monitoring through the application of pharmacokinetic concepts to optimize individual drug therapy. OBJECTIVE: This research proposes to evaluate the tacrolimus pharmacokinetic parameters in patients suspected of acute kidney graft rejection under methylprednisolone pulse therapy. METHODS: Eleven adult tacrolimus-treated renal recipients were selected from a prospective, single-arm, single-center cohort study, with suspicion of acute rejection although in use of methylprednisolone pulses therapy. They were followed up for three months posttransplantation, being tacrolimus trough serum concentrations determined using a chemiluminescent magnetic immunoassay, and pharmacokinetic parameters were estimated by using a nonlinear mixed-effects model implemented by Monolix 2020R1. A tacrolimus trough serum concentration range of 8 to 12 ng.mL-1 was considered therapeutic. RESULTS: Six patients showed acute cellular rejection, and two of them in addition had an antibody- mediated rejection. Tacrolimus trough serum concentration was below the reference range in eight patients. Most patients showed a high tacrolimus concentration intrapatient and pharmacokinetic parameters variability. CONCLUSION: The obtained pharmacokinetics parameters helped in understanding the kidney recipient patients' tacrolimus behavior, assisting in the improvement of individual drug therapy and reducing the risk of acute rejection episodes.

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Introducción: En Colombia, la información sobre la frecuencia de presentación de la enfermedad por CO-VID-19 y sus desenlaces en personas con esclerosis múltiple (EM) es prácticamente inexistente. El objetivo de este estudio es describir la frecuencia, las características y los factores relacionados con la infección por COVID-19 en una muestra de pacientes con EM en Colombia. Materiales y métodos: Análisis descriptivo y retrospectivo de pacientes diagnosticados con criterios de esclerosis múltiple que acudieron a nuestro centro entre junio y octubre del año 2021. Los pacientes proporcionaron información sobre la infección por SARS-CoV-2 y su vacunación. Se analizaron los factores relacionados con la infección por COVID-19 mediante modelos de regresión logística binomial uni y multivariable. Resultados: Se analizaron 240 pacientes, de los cuales el 71 % eran mujeres, con una edad promedio de 34 años. La mayoría estaban en tratamiento con terapias modificadoras de la enfermedad y más del 80 % estaban vacunados. Sesenta y nueve pacientes declararon haber tenido COVID-19. En los modelos multivariables, la edad (OR 0,96; IC 95 % 0,93-0,99) fue el único factor asociado con una menor probabilidad de infección por COVID-19. Discusión: La infección por COVID-19 en pacientes con EM en Colombia parece ser independiente de las variables clínicas y de tratamiento y parece estar asociada con la menor edad. Conclusiones: Se requieren más estudios para evaluar el comportamiento del COVID-19 en pacientes con EM en el contexto colombiano.

Introduction: The information about the frequency of COVID-19 and its outcomes in people with Multiple Sclerosis (MS) in Colombia is practically non-existent. We aimed to describe the frequency characteristics and factors associated with of COVID-19 in a sample of patients with MS. Materials and methods: Descriptive and retrospective analysis of patients diagnosed with Multiple Sclerosis criteria who attended our center between June and October 2021. Patients provided information about SARS-CoV-2 infection and their vaccination. COVID-19 determinants were analyzed using uni-and multivariable binomial logistic regression models. Results: 240 patients were analyzed, of whom 71% were women, with a mean age of 34 years. The majority of patients were on disease-modifying therapies and over 80 % were vaccinated. 69 patients reported having had COVID-19. In multivariable models, age (OR 0.96; 95 % CI 0.93-0.99) was the only factor associated with a lower odds of COVID-19 infection. Discussion: COVID-19 infection in patients with MS in Colombia appears to be independent of clinical and treatment variables, and it appears to be associated with younger age. Conclusions: More studies are needed to assess the behavior of COVID-19 in MS patients from Colombia.

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Los pacientes con malignidades hematológicas tienen un riesgo más alto de hospitalización, admisión a cuidado crítico y muerte cuando contraen COVID-19. En este grupo se ha propuesto la vacunación y los refuerzos para disminuir el riesgo de complicaciones. Sin embargo, es posible ver una pobre respuesta humoral y celular a las vacunas. En esta revisión se presenta la evidencia sobre la respuesta a la vacunación, poniendo de presente algunas patologías y tratamientos que pueden disminuirla de forma significativa. Los pacientes con neoplasias hematológicas se deben considerar en riesgo de complicaciones, incluso después de haber sido vacunados de forma completa y haber recibido los refuerzos. Se debe mantener la vigilancia de forma estrecha después de haber sido vacunados y evaluar la posibilidad de otras estrategias (medicamentos, anticuerpos monoclonales) para la prevención o el manejo de COVID-19.

Patients with hematological malignancies have a higher risk of hospital admission, critical care and death when they suffer from COVID-19. In this group of patients, vaccination and boosters have been proposed to mitigate the risk of complications. However, it is possible to observe a diminished rate of humoral and cellular response. In this review, evidence is shown about the response to COVID-19 vaccination, considering some specific pathologies and treatments that can affect such response in a significant account. Patients with malignant neoplasm must be considered at risk of COVID-19 complications, even after a complete vaccine schedule and boosters. Surveillance must be maintained after vaccination over these patients and other strategies must be considered (drugs, monoclonal antibodies) for prevention and management of COVID-19.

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Exponemos la experiencia del Instituto Nacional de Cardiología de una serie de casos de pacientes sometidos a trasplante cardiaco entre mayo de 2016 y junio 2022. Se realizaron 14 trasplantes, 13 fueron del sexo masculino. La edad osciló entre 19 y 62 años. Las etiologías fueron cardiopatías de tipo idiopática en 57% y valvular en 21%. El 50% se trasplantó en INTERMACS 4 (Interagency Registry for Mechanically Assisted Circulatory Support), 21% INTERMACS 3 y solo 28% en INTERMACS 2. Tres pacientes se trasplantaron con asistencia circulatoria tipo membrana circulación extracorpórea. Las complicaciones más frecuentes fueron las infecciosas. La mortalidad hospitalaria fue 35,7%. Hubo un fallecido en el seguimiento tras 5 años de trasplante.

We present the experience of the National Institute of Cardiology of a series of cases of patients undergoing heart transplantation between May 2016 and June 2022. Fourteen transplants were performed, 13 of the patients were male. The age ranged between 19 and 62 years. The etiologies were idiopathic heart disease in 57% and valvular heart disease in 21%. Fifty percent was transplanted in INTERMACS 4 (Interagency Registry for Mechanically Assisted Circulatory Support), 21% in INTERMACS 3 and only 28% in INTERMACS 2. Three patients were transplanted with membrane type extracorporeal circulation circulatory support. The most frequent complications were infectious. Hospital mortality was 35.7%. There was one patient who died during follow-up after 5 years of transplantation.

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ABSTRACT Objective: To evaluate the etiology of and factors associated with pulmonary infection in kidney and kidney-pancreas transplant recipients. Methods: This was a single-center case-control study conducted between December of 2017 and March of 2020 at a referral center for kidney transplantation in the city of Belo Horizonte, Brazil. The case:control ratio was 1:1.8. Cases included kidney or kidney-pancreas transplant recipients hospitalized with pulmonary infection. Controls included kidney or kidney-pancreas transplant recipients without pulmonary infection and matched to cases for sex, age group, and donor type (living or deceased). Results: A total of 197 patients were included in the study. Of those, 70 were cases and 127 were controls. The mean age was 55 years (for cases) and 53 years (for controls), with a predominance of males. Corticosteroid use, bronchiectasis, and being overweight were associated with pulmonary infection risk in the multivariate logistic regression model. The most common etiologic agent of infection was cytomegalovirus (in 14.3% of the cases), followed by Mycobacterium tuberculosis (in 10%), Histoplasma capsulatum (in 7.1%), and Pseudomonas aeruginosa (in 7.1%). Conclusions: Corticosteroid use, bronchiectasis, and being overweight appear to be risk factors for pulmonary infection in kidney/kidney-pancreas transplant recipients, endemic mycoses being prevalent in this population. Appropriate planning and follow-up play an important role in identifying kidney and kidney-pancreas transplant recipients at risk of pulmonary infection.

RESUMO Objetivo: Avaliar a etiologia da infecção pulmonar e os fatores a ela associados em pacientes que receberam transplante de rim ou rim-pâncreas. Métodos: Estudo unicêntrico de caso-controle realizado entre dezembro de 2017 e março de 2020 em um centro de referência em transplantes de rim em Belo Horizonte (MG). A proporção caso:controle foi de 1:1,8. Os casos foram pacientes que haviam recebido transplante de rim ou rim-pâncreas e que foram hospitalizados em virtude de infecção pulmonar. Os controles foram pacientes que haviam recebido transplante de rim ou rim-pâncreas e que não apresentaram infecção pulmonar, emparelhados com os casos pelo sexo, faixa etária e tipo de doador (vivo ou falecido). Resultados: Foram incluídos no estudo 197 pacientes. Destes, 70 eram casos e 127 eram controles. A média de idade foi de 55 anos (casos) e 53 anos (controles), com predomínio de pacientes do sexo masculino. O uso de corticosteroides, bronquiectasias e sobrepeso relacionaram-se com risco de infecção pulmonar no modelo de regressão logística multivariada. O agente etiológico de infecção mais comum foi o citomegalovírus (em 14,3% dos casos), seguido de Mycobacterium tuberculosis (em 10%), Histoplasma capsulatum (em 7,1%) e Pseudomonas aeruginosa (em 7,1%). Conclusões: O uso de corticosteroides, bronquiectasias e sobrepeso parecem ser fatores de risco de infecção pulmonar em pacientes que receberam transplante de rim ou rim-pâncreas, e as micoses endêmicas são prevalentes nessa população. O planejamento e acompanhamento adequados desempenham um papel importante na identificação de pacientes transplantados de rim/rim-pâncreas nos quais haja risco de infecção pulmonar.

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Introduction Chagas disease is an important public health problem in Latin American countries, affecting 6 million people within the region. In patients with chronic Chagas disease who undergo some type of immunosuppression reactivation of the acute form may occur, and manifestations involve many organs, including the central nervous system. Tumor-like brain reactivations are well described in patients with acquired immunodeficiency syndrome; however, this is a very rare event among Chagasic patients immunosuppressed after a heart transplantation. Case Report We describe three cases of cardiac transplant patients who had a tumor-like intracranial lesion, whose biopsies were compatible with Chagas disease. All 3 patients were treated with benznidazole, and 2 of them presented parameters of cure after 60 days of treatment, while 1 required a 2nd cycle of treatment. Discussion A tumor-like Chagas disease reactivation in the central nervous system may happen in heart-transplant patients and, due to the multiple differential diagnoses, we believe that brain biopsies should be considered when feasible

Introdução A doença de Chagas é um problema de saúde pública relevante nos países da América Latina, afetando aproximadamente 6 milhões de pessoas na região. Em pacientes com a forma crônica da doença submetidos a algum tipo de imunossupressão, a reativação da forma aguda pode ocorrer e cursar com manifestações que envolvem vários órgãos, incluindo o sistema nervoso central. A reativação cerebral pseudotumoral é bem descrita em pacientes imunossuprimidos pela síndrome de imunodeficiência adquirida; contudo, é um evento raro entre os pacientes imunossuprimidos após transplante cardíaco. Relato de caso São relatados três casos de transplantados cardíacos que apresentavam uma lesão tumoral intracraniana, cujas biópsias eram compatíveis com a doença de Chagas. Todos os 3 pacientes foram tratados com benznidazol, e 2 deles apresentaram parâmetros de cura após 60 dias de tratamento, enquanto 1 exigiu um 2° ciclo de tratamento. Discussão A reativação pseudotumoral da doença de Chagas no sistema nervoso central pode acontecer em pacientes submetidos ao transplante cardíaco e, devido aos múltiplos diagnósticos diferenciais, acreditamos que a biópsia cerebral deve ser considerada quando viável.

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Belimumabe, rituximabe, terapia imunossupressora. Indicação: Nefrite lúpica nos estágios III, IV, V, refratária à terapia imunossupressora. Pergunta: Belimumabe é eficaz (remissão da nefrite, normalização da perda da função renal, qualidade de vida) e seguro (descontinuação devido a eventos adversos totais e eventos adversos graves) para o tratamento de pacientes com nefrite lúpica refratária nos estágios III, IV, V em comparação aos medicamentos disponíveis no Sistema Único de Saúde? Objetivo: Avaliar a segurança e eficácia do belimumabe em comparação com os medicamentos disponíveis no Sistema Único de Saúde em pacientes adultos com nefrite lúpica. Métodos: Revisão rápida de revisões sistemáticas. Levantamento bibliográfico foi realizado nas bases de dados PUBMED, EMBASE, SCOPUS, BVS, EPISTEMONIKOS, Cochrane Library e em registros de revisões sistemáticas e ensaios clínicos. Seguiu estratégias de buscas predefinidas. Foi feita avaliação da qualidade metodológica dos estudos incluídos através da ferramenta AMSTAR-2 (Assessing the Methodological Quality of Systematic Reviews Version 2). Resultados: Foram selecionadas duas revisões sistemáticas que atendiam aos critérios de elegibilidade, mas nenhum ensaio clínico foi escolhido, pois não atendiam aos critérios de inclusão. Conclusão: a terapia combinada de belimumabe, ou de rituximabe, com tratamento imunossupressor padrão é mais eficaz que o tratamento padrão para alcançar remissão clínica da nefrite lúpica. A terapia combinada é tão segura quanto o tratamento padrão. Belimumabe e rituximabe tem eficácia similar entre si

Belimumab, rituximab, and immunosuppressive therapy. Indication: Refractory lupus nephritis to immunosuppressive therapy in stages III, IV, V. Question: Is belimumab effective (for remission of nephritis, normalization of loss of renal function, quality of life) and safe (for discontinuation due to total adverse events and serious adverse events) in the treatment of patients with refractory lupus nephritis in stages III, IV, V compared to the drugs available in the Brazilian Public Health System? Objective: To evaluate the safety and efficacy of belimumab compared to drugs available in the Brazilian Public Health System in adult patients with lupus nephritis. Methods: Rapid review of systematic reviews. A bibliographic search was done in the PUBMED, EMBASE, SCOPUS, BVS, EPISTEMONIKOS, Cochrane Library databases and in records of systematic reviews and clinical trials. It has followed predefined search strategies. The methodological quality of the included studies was evaluated using the AMSTAR-2 tool (Assessing the Methodological Quality of Systematic Reviews Version 2). Results: Two systematic reviews were selected, which met the eligibility criteria, but no clinical trials were chosen, as they did not meet the inclusion criteria. Conclusion: Combination therapy of belimumab or rituximab with standard immunosuppressive treatment is more effective than standard treatment in achieving clinical remission of lupus nephritis. Combination therapy is as safe as standard treatment. Belimumab and rituximab have similar efficacy to each other

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Background: Tuberculin skin test (TST) has played an essential in the diagnosis of latent tuberculosis infection (LTBI) for nearly a century. Objective: This study aimed to investigate the general characteristics of patients tested with TST in a tertiary hospital within two years. Methods: All patients who were evaluated to screen for tuberculosis and received a TST were included. The Mantoux method was used for TST administration. Results: A total of 661 patients, 345 (52.2%) men and 316 (47.8%) women, with a mean age of 43.0 ±15.9 years, were included in the study. Accordingly, TST was performed prior to anti-TNF biological agent therapy for 50% (331) of the participants, for LTBI screening before solid organ and/or hematological stem cell transplantation for 20.4% (135), for screening following contact with tuberculosis for 25.1% (166), for screening of healthcare professionals for 1.1% (7), and medical report for 3.3% (22). 2.7% of the patients who took TST were diagnosed with active tuberculosis (14 with pulmonary tuberculosis and 4 with extrapulmonary tuberculosis). QuantiFERON-TB Gold (QFT) test was performed in 332 (50.2%) patients with anergic TST results. According to TST and QFT test results, 28.3% (187) of the patients were started on tuberculosis prophylaxis. Conclusion: While TST is most performed for LTBI screening prior to biological agent therapy, almost one-fourth of patients taking TST require tuberculosis prophylaxis. On the other hand, about half of the patients require an additional QFT test.

Antecedentes: La prueba de la tuberculina ha jugado un papel fundamental en el diagnóstico de la infección latente por tuberculosis durante casi un siglo. Objetivo: Investigar las características generales de los pacientes a los que se les realizó la prueba de tuberculina en un hospital de tercer nivel. Métodos: Se incluyeron todos los pacientes que fueron incluidos en un tamizaje de tuberculosis mediante la prueba de tuberculina. Se utilizó el método de Mantoux para la administración de esta prueba. Resultados: Se incluyeron en el estudio un total de 661 pacientes, 345 (52.2%) hombres y 316 (47.8%) mujeres, con una edad media de 43.0 ±15.9 años. La prueba de tuberculina se realizó en el 50% (331) de los participantes, antes de la terapia con agentes biológicos anti-TNF; En el 20.4% (135) se hizo la prueba antes del trasplante de órganos sólidos y/o células madre hematológicas; para el 25.1% (166) se realizó tras contacto con la tuberculosis, el 1.1% (7) para tamizaje de los profesionales sanitarios y con informe médico para el 3.3% (22). El 2.7% de los pacientes que se realizaron la prueba de tuberculina fueron diagnosticados con tuberculosis activa (14 pulmonar y 4 extrapulmonar). La prueba QuantiFERON-TB Gold (QFT) se realizó en 332 (50.2 %) pacientes con resultados anérgicos para tuberculina. Según los resultados de las pruebas de tuberculina y QFT, el 28.3% (187) de los pacientes iniciaron profilaxis antituberculosa. Conclusión: Si bien la prueba de tuberculina se realiza comúnmente para la detección de tuberculosis latente antes de la terapia con agentes biológicos, casi una cuarta parte de los pacientes que se les hizo la prueba de tuberculina requieren profilaxis para tuberculosis. Por otro lado, aproximadamente la mitad de los pacientes requieren una prueba QFT adicional.

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Patients with leprosy may experience a chronic and severe type II leprosy reaction (ENL) erythema nodosum leprosum that may not respond to thalidomide and systemic immunosuppressants or may even cause serious adverse events. We here present four patients in whom anti-TNF-α therapy was used with successful results and compare our findings with other published cases. Four patients with chronic and severe ENL who did not respond to, at least, thalidomide and steroids (high doses) were followed up at two reference centers in Brazil. A thorough laboratory investigation was performed to exclude tuberculosis and other diseases before the start of immunobiological medication. Three patients were started on etanercept, and one patient was started on adalimumab. Of all patients, three developed severe adverse events resulting from the use of classical immunosuppressants for ENL (cataracts, deep vein thrombosis, diabetes, and osteoporosis). In all cases, a reduction in the number of ENL and, at least half of the immunosuppressant dose between 6 months and 2 years, were observed. Long-term follow-up of one patient revealed a dramatic reduction in hospital admissions due to ENL, from 12 instances in 1 year (before biologic therapy) to none (after biologic therapy), along with an improvement in condyloma acuminatum. In addition, no direct adverse events were observed with biologics. Treatment with anti-TNF-α therapy may be used as an alternative in patients with chronic and severe ENL who do not respond to traditional treatment (e.g., thalidomide, steroids, and other immunosuppressants). This treatment can help reduce the frequency of ENL, the immunosuppressive burden, and the number of hospital admissions.

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PURPOSE: The F3II cell line is a highly invasive variant of mammary carcinoma. Although it is frequently used as a model to evaluate the efficacy of immunotherapy, its impact on the immune system remains poorly understood. The main objectives of this study were to evaluate the effects of F3II tumors on the development of chronic inflammation and to characterize tumor-associated immunosuppression. METHODS: Following the experimental implantation of F3II tumors in BALB/c mice, alterations in the liver and spleen anatomy and the numbers of circulating leukocytes, myeloid-derived suppressor cells (MDSCs), and regulatory T cells were measured using hematological techniques, histopathological analysis, and flow cytometry. The capacity of the F3II tumor-bearing mice to reject MB16F10 allogeneic tumor transplantation was also evaluated. In addition, the restoration of immune parameters in tumor-bearing mice was evaluated after standard breast cancer chemotherapy and surgical tumor excision. RESULTS: F3II tumor implantation increased the levels of chronic inflammatory markers, such as the neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios, and caused myeloid alterations, including extramedullary granulopoiesis and megakaryopoiesis, along with the recruitment of MDSCs to the spleen. Chemotherapy or surgical F3II tumor removal completely rescued the tumor-associated extramedullary granulopoiesis and megakaryopoiesis. Notably, the presence of F3II tumors reduced the capacity of BALB/c mice to reject MB16F10 allogeneic tumor transplantation. CONCLUSION: These results support the occurrence of F3II tumor-mediated immune cell dysfunction, which mimics the immune alterations characterized by chronic systemic inflammation and immunosuppression observed in breast cancer in clinical settings. Thus, the F3II tumor model is relevant for evaluating novel breast cancer immunotherapies and combinations in preclinical studies. This model could also be useful for identifying appropriate therapeutic targets and developing proof-of-concept experiments in the future.

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Background: Tuberculin skin test (TST) has played an essential in the diagnosis of latent tuberculosis infection (LTBI) for nearly a century. Objective: This study aimed to investigate the general characteristics of patients tested with TST in a tertiary hospital within two years. Methods: All patients who were evaluated to screen for tuberculosis and received a TST were included. The Mantoux method was used for TST administration. Results: A total of 661 patients, 345 (52.2%) men and 316 (47.8%) women, with a mean age of 43.0 ±15.9 years, were included in the study. Accordingly, TST was performed prior to anti-TNF biological agent therapy for 50% (331) of the participants, for LTBI screening before solid organ and/or hematological stem cell transplantation for 20.4% (135), for screening following contact with tuberculosis for 25.1% (166), for screening of healthcare professionals for 1.1% (7), and medical report for 3.3% (22). 2.7% of the patients who took TST were diagnosed with active tuberculosis (14 with pulmonary tuberculosis and 4 with extrapulmonary tuberculosis). QuantiFERON-TB Gold (QFT) test was performed in 332 (50.2%) patients with anergic TST results. According to TST and QFT test results, 28.3% (187) of the patients were started on tuberculosis prophylaxis. Conclusion: While TST is most performed for LTBI screening prior to biological agent therapy, almost one-fourth of patients taking TST require tuberculosis prophylaxis. On the other hand, about half of the patients require an additional QFT test.

Antecedentes: La prueba de la tuberculina ha jugado un papel fundamental en el diagnóstico de la infección latente por tuberculosis durante casi un siglo. Objetivo: Investigar las características generales de los pacientes a los que se les realizó la prueba de tuberculina en un hospital de tercer nivel. Métodos: Se incluyeron todos los pacientes que fueron incluidos en un tamizaje de tuberculosis mediante la prueba de tuberculina. Se utilizó el método de Mantoux para la administración de esta prueba. Resultados: Se incluyeron en el estudio un total de 661 pacientes, 345 (52.2%) hombres y 316 (47.8%) mujeres, con una edad media de 43.0 ±15.9 años. La prueba de tuberculina se realizó en el 50% (331) de los participantes, antes de la terapia con agentes biológicos anti-TNF; En el 20.4% (135) se hizo la prueba antes del trasplante de órganos sólidos y/o células madre hematológicas; para el 25.1% (166) se realizó tras contacto con la tuberculosis, el 1.1% (7) para tamizaje de los profesionales sanitarios y con informe médico para el 3.3% (22). El 2.7% de los pacientes que se realizaron la prueba de tuberculina fueron diagnosticados con tuberculosis activa (14 pulmonar y 4 extrapulmonar). La prueba QuantiFERON-TB Gold (QFT) se realizó en 332 (50.2 %) pacientes con resultados anérgicos para tuberculina. Según los resultados de las pruebas de tuberculina y QFT, el 28.3% (187) de los pacientes iniciaron profilaxis antituberculosa. Conclusión: Si bien la prueba de tuberculina se realiza comúnmente para la detección de tuberculosis latente antes de la terapia con agentes biológicos, casi una cuarta parte de los pacientes que se les hizo la prueba de tuberculina requieren profilaxis para tuberculosis. Por otro lado, aproximadamente la mitad de los pacientes requieren una prueba QFT adicional.

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Rapidly progressive glomerulonephritis (RPGN) is a syndrome which presents rapid loss of renal function. Vasculitis represents one of the major causes, often related to anti-neutrophil cytoplasmic antibodies (ANCA). Herein, we report a case of methimazole-induced ANCA-associated vasculitis. A 35-year-old woman complained of weight loss and fatigue for 2 weeks and attended the emergency room with alveolar hemorrhage. She had been diagnosed with Graves' disease and had been taking methimazole in the past 6 months. Her physical examination showed pulmonary wheezing, hypertension and signs of respiratory failure. Laboratory tests revealed urea 72 mg/dL, creatinine 2.65 mg/dL (eGFR CKD-EPI: 20 mL/min/1.73 m2), urine analysis with >100 red blood cells per high-power field, 24 h-proteinuria: 1.3 g, hemoglobin 6.6 g/dL, white-cell count 7700/mm3, platelets 238,000/mm3, complement within the normal range, negative viral serological tests and ANCA positive 1:80 myeloperoxidase pattern. Chest tomography showed bilateral and diffuse ground-glass opacities, and bronchial washing confirming alveolar hemorrhage. A renal biopsy using light microscopy identified 27 glomeruli (11 with cellular crescentic lesions), focal disruption in glomerular basement membrane and fibrinoid necrosis areas, tubulitis and mild interstitial fibrosis. Immunofluorescence microscopy showed IgG +2/+3, C3 +3/+3 and Fibrinogen +3/+3 in fibrinoid necrosis sites. She was subsequently diagnosed with crescentic pauci-immune glomerulonephritis, mixed class, in the setting of a methimazole-induced ANCA vasculitis. The patient was treated with methimazole withdrawal and immunosuppressed with steroids and cyclophosphamide. Four years after the initial diagnosis, she is currently being treated with azathioprine, and her exams show creatinine 1.30 mg/dL (eGFR CKD-EPI: 52 mL/min/1.73 m2) and negative p-ANCA.

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When it is safe to proceed with transplantation after coronavirus disease 2019 (COVID-19) infection is still unknown. We describe the clinical course and management of immunosuppression in a patient with positive real-time polymerase chain reaction (RT-PCR) for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in a nasopharyngeal swab at the time of kidney transplantation, and with positive antibodies for SARS-CoV-2. The patient had no complications and was discharged with a functioning graft.