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INTRODUCCION: El rechazo se define como un aumento en el nivel de creatinina sérica des-pués de la exclusión de otras causas de disfunción del injerto, asociado a cambios patológicos específicos en el injerto y puede ocurrir en cualquier momento después del trasplante.OBJETIVO: Determinar el tiempo de sobrevida del injerto renal en pacientes trasplantados renales con Rechazo Activo.MATERIALES Y MÉTODOS: Estudio observacional, descriptivo, transversal, se realizó en el Hospital de Especialidades Carlos Andrade Marín en el periodo 2013-2022, el universo se con-formó por una base de datos anonimizada de 460 pacientes trasplantados, de los cuales 92 pacientes (20 %) presentaron diagnóstico de rechazo activo. Se utilizó el programa estadístico SPSS v26®.RESULTADOS: El 60,8% fueron pacientes de sexo masculino, con una edad media de 43,7 años, la supervivencia del aloinjerto en pacientes con rechazo fue del 85% a los 5 años de seguimiento, y de los que no tuvieron rechazo fue del 97,1 % a los 5 años con una (p =0,001). El rechazo mediado por células T presentó una mayor sobrevida del injerto renal del 97% y la menor tasa de sobrevida se evidenció en el rechazo mediado por anticuerpos.DISCUSIÓN. La incidencia del rechazo del injerto renal a nivel global se estima del 5% al 10%, aunque puede ser mayor hasta el 35%, en el grupo de alto riesgo inmunológico. La sobrevida del aloinjerto empeora con cada episodio de rechazo comparado con pacientes que no experi-mentan rechazo del injerto.CONCLUSIÓN: La tasa más alta de sobrevida se evidenció en pacientes sin rechazo durante 5 años de seguimiento, corroborando lo hallado en el estado del arte. En este estudio la super-vivencia del rechazo mediado por células T fue superior en relación con el rechazo mediado por anticuerpos.

Rejection is defined as an increase in serum creatinine level after exclusion of other causes of injectable dysfunction, associated with specific pathological changes in the injectable and may occur at any time after transplantation.OBJECTIVE: Determine the survival time of the kidney graft in kidney transplant patients with Active Rejection.MATERIALS AND METHODS: Observational, descriptive, cross-sectional study was carried out at the Carlos Andrade Marín Specialty Hospital in the period 2013-2022, the universe was made up of an anonymized database of 460 transplant patients, of which 92 patients (20 %) presented a diagnosis of active rejection. The SPSS v26® statistical program was used. RESULTS: 60.8% were male patients, with a mean age of 43.7 years, allograft survival in pa-tients with rejection was 85% at 5 years of follow-up, and of those who did not have rejection it was 97.1% at 5 years with one (p =0.001). Rejection mediated by T cells presented a greater survival rate of the kidney graft of 97% and the lowest survival rate was evident in rejection mediated by antibodies.DISCUSSION. The incidence of kidney graft rejection globally is estimated at 5% to 10%, al-though it can be higher, up to 35%, in the high immunological risk group, with increasing preva-lence. Allograft survival worsens with each episode of rejection compared to patients who do not experience graft rejection.CONCLUSION: The highest survival rate was evident in patients without rejection during 5 years of follow-up, corroborating what was found in the state of the art in this study, the survival of rejection mediated by T cells was superior in relation to rejection mediated by antibodies.

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Objetivo: esta investigación tuvo por objetivo describir la adherencia al tratamiento inmunosupresor en pacientes trasplantados renales. Material y métodos: estudio de tipo cuantitativo, descriptivo, transversal y observacional. Población: trasplantados renales asistidos en una institución de salud de la ciudad de Corrientes, en el período de marzo 2018 ­ marzo 2023. Se utilizó un cuestionario confecciona-do a partir de 2 escalas de medición, ITAS e ITBS. La información recolectada se analizó mediante un programa informático Excel. Se encuestó a 23 pacientes trasplantados renales. Resultados: el 92% presentó adherencia al tratamiento inmunosupresor, la edad media fue de 43 años y el 57% son de sexo femenino. Con respecto a la variable que evalúa las barreras incontrolables para la adherencia al tratamiento inmunosupresor en los últimos tres meses, es relevante destacar que un 87% de los participantes informa una disminución en estas barreras, y en relación con la variable sobre las barreras controlables que perciben los pacientes para adherirse al tratamiento inmunosupresor en los últimos 3 meses, se observó que el 100% de los encuestados posee menor presencia de barreras controlables. Por último, la adherencia al tratamiento inmunosupresor según edad y sexo. Conclusión: se resalta una alta adherencia al tratamiento inmunosupresor en trasplante renal, 92% de los participantes. La mejora en las barreras incontrolables sugiere un avance positivo en la gestión del tratamiento. Aunque hay divergencias con otros estudios, la percepción mínima de barreras controlables indica un compromiso general de los pacientes (AU)

Objective: this research aimed to describe adherence to immunosuppressive treatment in kidney transplant patients. Material and methods: quantitative, descriptive, cross-sectional and observational study. Population: kidney transplant recipients assisted in a health institution in the city of Corrientes, in the period from March 2018 to March 2023. A questionnaire was used based on 2 measurement scales, ITAS and ITBS. The information collected was analyzed using an Excel computer program. 23 kidney transplant patients were surveyed. Results: 92% adhered to immunosuppressive treatment, the average age was 43 years and 57% were female. With respect to the variable that evaluates uncontrollable barriers to adherence to immunosuppressive treatment in the last three months, it is relevant to highlight that 87% of the participants report a decrease in these barriers, and in relation to the variable on controllable barriers that perceived by patients to adhere to immunosuppressive treatment in the last 3 months, it was observed that 100% of those surveyed have a lower presence of controllable barriers. Finally, adherence to immunosuppressive treatment according to age and sex. Conclusion: high adherence to immunosuppressive treatment in kidney transplantation is highlighted, 92% of participants. Improvement in uncontrollable barriers suggests positive progress in treatment management. Although there are divergences with other studies, the minimal perception of controllable barriers indicates a general commitment of patients (AU)

Objetivo: esta pesquisa teve como objetivo descrever a adesão ao tratamento imunossupressor em pacientes transplantados renais. Material e métodos: estudo quantitativo, descritivo, transversal e ob-servacional. População: receptores de transplante renal atendidos em uma instituição de saúde da cidade de Corrientes, no período de março de 2018 a março de 2023. Foi utilizado questionário baseado em 2 escalas de medida, ITAS e ITBS. A informação recolhida foi analisada através de um programa informático Excel. Fo-ram pesquisados 23 pacientes transplantados renais. Resultados: 92% aderiram ao tratamento imunossupressor, a média de idade foi de 43 anos e 57% eram do sexo feminino. Com relação à variável que avalia as barreiras incontroláveis à adesão ao tratamento imunossupressor nos últimos três meses, é relevante destacar que 87% dos participantes relatam diminuição dessas barreiras, e em relação à variável sobre barreiras controláveis que percebidas pelos adesão dos pacientes ao tratamento imunossupressor nos últimos 3 meses, observou-se que 100% dos pesquisados apresentam menor presença de barreiras controláveis. Por fim, adesão ao tratamento imunossupressor de acordo com idade e sexo. Conclusão: destaca-se a elevada adesão ao tratamento imunossupressor no transplante re-nal, 92% dos participantes. A melhoria nas barreiras incontroláveis sugere progresso positivo na gestão do tratamento. Embora existam divergências com outros estudos, a percepção mínima de barreiras controláveis indica um comprometimento geral dos pacientes (AU)

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SUMMARY: Although tacrolimus (TAC) significantly reduces allograft rejection incidence in solid-organ transplantation, its long-term use is associated with an increased risk of TAC-induced nephrotoxicity. In this study, we investigated the renoprotective effects of green tea extract (GTE) with or without the dipeptidyl peptidase 4 inhibitor, gemigliptin, by assessing serum creatinine levels, the amount of proteinuria, and histopathology in TAC-induced nephrotoxicity. TAC-induced nephrotoxicity was induced by intraperitoneal TAC injection, GTE was administered via subcutaneous injection, and gemigliptin was administered orally. Mice with TAC-induced nephrotoxicity exhibited a significant increase in both serum creatinine levels and 24-hour urine protein. However, when treated with GTE via subcutaneous injection, mice showed a decrease in serum creatinine levels and the amount of proteinuria. When GTE was combined with gemigliptin, further renoprotective effects were observed in biochemical assessments, consistent with the attenuation of TAC-induced nephrotoxicity in histopathology. The expression of p53 protein was lower in the mice treated with the combination of GTE and gemigliptin compared to mice with TAC-induced nephrotoxicity. Our results demonstrate that the combination of GTE and gemigliptin treatment reveals synergistic renoprotective effects by decreasing the expression of p53 protein. These findings suggest that the combination of GTE and gemigliptin could potentially be used as a prophylactic or therapeutic strategy for TAC-induced nephrotoxicity.

Aunque tacrolimus (TAC) reduce significativamente la incidencia de rechazo de aloinjertos en trasplantes de órganos sólidos, su uso a largo plazo se asocia con un mayor riesgo de nefrotoxicidad inducida por TAC. En este estudio, investigamos los efectos renoprotectores del extracto de té verde (GTE) con o sin el inhibidor de la dipeptidil peptidasa 4, gemigliptina, mediante la evaluación de los niveles de creatinina sérica, la cantidad de proteinuria y la histopatología en la nefrotoxicidad inducida por TAC. La nefrotoxicidad inducida por TAC se indujo mediante inyección intraperitoneal de TAC, el GTE se administró mediante inyección subcutánea y la gemigliptina se administró por vía oral. Los ratones con nefrotoxicidad inducida por TAC mostraron un aumento significativo tanto en los niveles de creatinina sérica como en la proteína en orina de 24 horas. Sin embargo, cuando se trataron con GTE mediante inyección subcutánea, los ratones mostraron una disminución en los niveles de creatinina sérica y en la cantidad de proteinuria. Cuando se combinó GTE con gemigliptina, se observaron efectos renoprotectores adicionales en las evaluaciones bioquímicas, lo que concuerda con la atenuación de la nefrotoxicidad inducida por TAC en histopatología. La expresión de la proteína p53 fue menor en los ratones tratados con la combinación de GTE y gemigliptina en comparación con los ratones con nefrotoxicidad inducida por TAC. Nuestros resultados demuestran que la combinación de tratamiento con GTE y gemigliptina revela efectos renoprotectores sinérgicos al disminuir la expresión de la proteína p53. Estos hallazgos sugieren que la combinación de GTE y gemigliptina podría usarse potencialmente como estrategia profiláctica o terapéutica para la nefrotoxicidad inducida por TAC.

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Objetivo: comparar o risco de infecção pelo vírus BK em pacientes transplantados renais tratados com dois diferentes esquemas terapêuticos. Além disso, avaliou-se a influência de fatores sociodemográficos no risco de infecção pelo vírus entre os dois grupos de tratamento. Métodos: realizou-se a pesquisa com dados coletados entre 2019 e 2023 a partir de prontuários eletrônicos, em um hospital universitário de Fortaleza. A análise estatística foi feita utilizando o software JAMOVI, sendo aplicados os testes qui-quadrado para avaliar a associação entre os fatores de risco e infecção por BKV e os testes ANOVA e teste t de Student para avaliar a associação entre os fatores de risco e o tempo médio de internação. Resultados: a avaliação estatística pelo teste T de Student não apresentou diferenças significativas no tempo de internação entre pacientes do sexo masculino e feminino (p>0,05), e o tempo de internação dos pacientes também não foi estatisticamente relacionado com o uso de corticosteroides na terapia imunossupressora (p>0,05), positividade para o BKV (p>0,05) e também não foi diferente com relação aos diversos esquemas de imunossupressão adotados (p>0,05). A análise estatística com o teste qui-quadrado não identificou uma associação significativa entre os imunossupressores utilizados e a infecção pelo o vírus BK pós-transplante. Conclusão: a prevalência da infecção pelo vírus está muito mais relacionada com a intensidade da imunossupressão do que a natureza dos imunossupressores utilizados, ressaltando a importância do monitoramento dos níveis séricos.

Objective: the main objective of this study was to compare the risk of BK virus infection in kidney transplant patients treated with two different therapeutic regimens. Furthermore, the influence of sociodemographic factors on the risk of virus infection between the two treatment groups was evaluated. Methods: we carried out research with data collected between 2019 and 2023 from electronic medical records in a university hospital in Fortaleza. Statistical analysis was performed using the JAMOVI software, using the chi-square test to evaluate the association between risk factors and BKV infection and the ANOVA and Student's T-test to evaluate the association between risk factors and BKV infection. average pace of internationalization. Results: statistical evaluation using the Student's T-test showed no significant differences in the length of stay between male and female patients (p>0.05), and the length of stay of patients was also not statistically related to the use of corticosteroids. In immunosuppressive therapy (p>0.05), positivity for BKV (p>0.05) and also not indifferent regarding the different immunosuppression regimens adopted (p>0.05). Statistical analysis with the chi-square test does not include a significant association between the immunosuppressants used and post-transplant BK virus infection. Conclusion: the prevalence of virus infection is much more related to the intensity of immunosuppression than the nature of the immunosuppressants used, highlighting the importance of monitoring serum levels.

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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.

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Objective To prepare mouse monoclonal antibodies against the ectodomain of E2 (E2ecto) glycoprotein of Western equine encephalitis virus (WEEV). Methods A prokaryotic expression plasmid pET-28a-WEEV E2ecto was constructed and transformed into BL21 (DE3) competent cells. E2ecto protein was expressed by IPTG induction and presented mainly as inclusion bodies. Then the purified E2ecto protein was prepared by denaturation, renaturation and ultrafiltration. BALB/c mice were immunized with the formulated E2ecto protein using QuickAntibody-Mouse5W as an adjuvant via intramuscular route, boosted once at an interval of 21 days. At 35 days post-immunization, mice with antibody titer above 1×104 were inoculated with E2ecto intraperitoneally, and spleen cells were fused with SP2/0 cells three days later. Hybridoma cells secreting specific monoclonal antibodies were screened by the limited dilution method, and ascites were prepared after intraperitoneal inoculation of hybridoma cells. The subtypes and titers of the antibodies in ascites were assayed by ELISA. The biological activity of the mAb was identified by immunofluorescence assay(IFA) on BHK-21 cells which were transfected with eukaryotic expression plasmid pCAGGS-WEEV-CE3E2E1. The specificity of the antibodies were evaluated with E2ecto proteins from EEEV and VEEV. Results Purified WEEV E2ecto protein was successfully expressed and obtained. Four monoclonal antibodies, 3G6G10, 3D7G2, 3B9E8 and 3D5B7, were prepared, and their subtypes were IgG2c(κ), IgM(κ), IgM(κ) and IgG1(κ), respectively. The titers of ascites antibodies 3G6G10, 3B9E8 and 3D7G2 were 105, and 3D5B7 reached 107. None of the four antibody strains cross-reacted with other encephalitis alphavirus such as VEEV and EEEV. Conclusion Four strains of mouse mAb specifically binding WEEV E2ecto are successfully prepared.

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Resumen El dicloruro de 1,1'-dimetil-4,4'-bipiridilo (Paraquat®) es un compuesto químico de la familia de las piridinas, utilizado como herbicida no selectivo y desecante. Este compuesto puede causar intoxicación aguda por todas las vías de exposición. En el momento, no hay un antídoto conocido y los tratamientos disponibles, incluidos los pediátricos, se basan en contrarrestar su absorción y propiciar su remoción oportuna. Se describe una serie de casos de 14 pacientes pediátricos, procedentes en su mayoría del departamento del Cauca, con intoxicación aguda por ingestión de paraquat. Los pacientes fueron remitidos y atendidos en un hospital de mediana a alta complejidad en el suroccidente colombiano, con un protocolo institucional para el manejo de la intoxicación aguda por el herbicida. La intoxicación aguda con paraquat por vía oral se asocia con una alta tasa de mortalidad, aún con atención médica oportuna, pues fácilmente se alcanzan concentraciones sistémicas para ser fulminante. Basado en la literatura disponible, el Hospital Universitario San José ha propuesto un protocolo clínico -adecuado para la intoxicación aguda por paraquat en población pediátrica- que incluye manejo estándar temprano, tratamiento inmunosupresor y antioxidante, y técnicas para su remoción sistémica

Abstract Paraquat®, or N,N'-dimethyl-4,4'-bipyridinium dichloride, is a bipyridyl compound used as a non-selective herbicide and desiccant that can cause acute poisoning through all routes of exposure. There is no known antidote, and the available treatments are based on avoiding its absorption and timely removing it, in adults and children. We describe a case series of 14 pediatric patients from the department of Cauca, Colombia, with acute intoxication after oral intake of paraquat. Patients were referred to a medium-high complexity hospital in southwestern Colombia and treated according to an institutional protocol for acute paraquat poisoning. Acute paraquat poisoning after oral ingestion is associated with a high mortality rate, even with timely medical attention, as the compound has no known antidote and quickly reaches systemic concentrations for fulminant poisoning. Based on the available literature, our center has proposed a clinical protocol including early standard management, immunosuppressive and antioxidant treatments, and systemic removal techniques. This protocol suggests an adequate approach to acute paraquat poisoning in the pediatric population.

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Abstract Objective To compare outcomes in patients with repeated implantation failure undergoing Intracytoplasmic Sperm Injection/In vitro fertilization (IVF/ICSI) plus immunosuppressants such as prednisolone, prednisone, or cyclosporine A versus the use of IVF/ICSI alone. Data source Databases were systematically searched in PubMed, Cochrane, and Embase databases in September 2023. Study Selection Randomized clinical trials and observational studies with the outcomes of interest were included. Data collect We computed odds ratios (ORs) for binary endpoints, with 95% confidence intervals (CIs). Heterogeneity was assessed using I2 statistics. Data were analyzed using Review Manager 5.4.The main outcomes were live birth, miscarriage, implantation rate, clinical pregnancy, and biochemical pregnancy. Data synthesis Seven studies with 2,829 patients were included. Immunosuppressive treatments were used in 1,312 (46.37%). Cyclosporine A improved implantation rate (OR 1.48; 95% CI 1.01-2.18) and clinical pregnancy (1.89, 95% CI 1.14-3.14). Compared to non-immunosuppressive treatment, prednisolone and prednisone did not improve live birth (OR 1.13, 95% CI 0.88-1.46) and miscarriage (OR 1.49, 95% CI 1.07-2.09). Prednisolone showed no significant effect in patients undergoing IVF/ICSI, clinical pregnancy (OR 1.34; 95% CI 0.76-2.36), or implantation rate (OR 1.36; 95% CI 0.76-2.42). Conclusion Cyclosporine A may promote implantation and clinical pregnancy rates. However, given the limited sample size, it is important to approach these findings with caution. Our results indicate that prednisolone and prednisone do not have any beneficial effects on clinical outcomes of IVF/ICSI patients with repeated implantation failure. PROSPERO CRD42023449655

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Objetivo: Los pacientes receptores de trasplante renal (TxR) tienen alta carga de comorbilidades y un riesgo aumentado de muerte por COVID-19. Nuestro objetivo es describir las manifestaciones y los desenlaces clínicos en un grupo de receptores de TxR con enfermedad por coronavirus 2019 (COVID-19) y definir factores asociados a mortalidad. Métodos: Estudio de corte transversal que incluyó la revisión retrospectiva de registros clínicos de pacientes receptores de TxR y diagnóstico de COVID-19 entre marzo de 2020 y febrero de 2022 en un centro de alta complejidad en Bogotá (Colombia). Se ejecutó un análisis bivariante y multivariante para establecer asociaciones entre las variables de interés y el desenlace en mortalidad. Resultados: Se incluyeron un total de 94 casos. El 71,28% tenía un TxR, principalmente de donante cadavérico. Las manifestaciones clínicas incluyeron la tos en el 79,7%, fiebre en el 50% y disnea en el 42,55% de los casos. La tasa de mortalidad global fue del 18,09%. En el 54,9% se realizó un ajuste inmunosupresor, con interrupción completa del esquema hasta en el 74% de estos casos. Conclusiones: La tasa de mortalidad evidenciada en receptores de TxR con COVID-19 es mayor que la descrita en la población general. La severidad de la COVID-19 en este grupo poblacional implica de forma frecuente la necesidad de ajustes a la terapia inmunosupresora. Los factores asociados a mortalidad fueron la disnea, la necesidad de intubación orotraqueal y de estancia en unidad de cuidados intensivos

Objective: Kidney transplant (KTx) recipients have a high burden of comorbidities and are at increased risk of death from coronavirus disease 2019 (COVID-19). Our objective is to describe the clinical manifestations and outcomes in a group of KTx recipients with COVID-19 and to define factors associated with mortality. Methods: Cross-sectional study that included the retrospective review of clinical records of KTx recipients diagnosed with COVID-19 between March 2020 and February 2022 in a transplant center in Bogotá (Colombia). A bivariate and multivariate analysis was performed to establish associations between the variables of interest and the primary outcome (mortality). Results: Ninety-four cases were included. 71.28% had a KTx, mainly from a cadaveric donor. Clinical manifestations included cough in 79.7%, fever in 50%, and dyspnea in 42.55% of cases. The overall mortality rate was 18.09%. In 54.9% an immunosuppressive adjustment was made, with complete interruption of the scheme in up to 74% of these cases. Conclusions: The mortality rate evidenced in KTx recipients with COVID-19 is higher than in general population. The severity of the COVID-19 in this group frequently requires adjustments to immunosuppressive therapy. The factors associated with mortality were dyspnea, the need for orotracheal intubation and intensive care unit sta

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La neumonía por Pneumocystis jirovecii es una enfermedad fúngica oportunista descrita principalmente en pacientes con VIH, sin embargo, tras la introducción de la TARV, ha incrementado su incidencia en pacientes con inmunosupresión no asociada a VIH, como neoplasias hematológicas y trasplantes de órganos sólidos. Presentamos el caso de un varón de 17 años, receptor de un trasplante renal, con inmunosupresión prolongada con corticoesteroides, con cuadro clínico de tos, disnea y fiebre. La TC mostró micronódulos pulmonares centrolobulillares y vidrio esmerilado. El LBA fue compatible con hemorragia alveolar difusa (HAD), con RPC positiva para P. jirovecii. Se descartaron otras infecciones y enfermedades autoinmunes. Recibió tratamiento con cotrimoxazol con buena evolución clínica y mejoría radiológica. Si bien las causas más frecuentes de HAD son etiologías autoinmunes como enfermedades reumatológicas o vasculitis, es prioritario descartar causas infecciosas, incluyendo P. jirovecii, ya que el tratamiento dirigido puede tener un impacto significativo en la mortalidad en este grupo de pacientes.

Pneumocystis jirovecii pneumonia is an opportunistic fungal infection, described mainly in HIV patients, however, after the introduction of ART, its presentation has increased in patients with non-HIV immunosuppression, such as hematological cancers, solid or hematopoietic stem cell transplantation. We report the case of a 17-year-old male, kidney transplant patient, with prolonged immunosuppression with corticoesteroids, with history of cough, dyspnea, and fever. Chest CT evidences centrilobular pulmonary micronodules with ground glass. BAL was performed compatible with diffuse alveolar hemorrhage, with positive PCR for P. jirovecii. Other infections and autoimmune disease were ruled out. He received treatment with cotrimoxazole with clinical improvement of the patient, and follow up chest CT at the end of treatment showed decrease of pulmonary infiltrates. Although the most frequent causes of DAH are autoimmune etiologies such as rheumatic diseases or vasculitis, it is a priority to rule out infectious causes, including P. jirovecii, since targeted treatment could have a significant impact on mortality outcomes in this group of patients.

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INTRODUCCIÓN. La nefropatía por poliomavirus BK resulta un problema emergente en el trasplante renal, pues contribuye a la pérdida temprana de los injertos renales. OBJETIVO. Caracterizar clínicamente a los pacientes trasplantados renales con nefropatía por poliomavirus BK. MATERIALES Y MÉTODOS. Estudio observacional, descriptivo, realizado en el Hospital de Especialidades Carlos Andrade Marín en el período 2013-2022, se obtuvo una base de datos anonimizada, 479 pacientes trasplantados renales, de estos se identificaron 37 pacientes que corresponde a un 7,7% con nefropatía por poliomavirus BK, se realizó un análisis con el programa estadístico SPSS v26®. RESULTADOS. La población estuvo caracterizada por pacientes del sexo masculino (56,8%), con una edad media de 48,2 años, el donante cadavérico fue el más frecuente (94,5%), la mayor parte del tratamiento de la nefropatía por poliomavirus BK consistió en cambio de micofenolato sódico a everolimus y se mantuvo con 50% de Tacrolimus y Prednisona (40,5%); al valorar el cambio de los valores de creatinina, los niveles más elevados fueros a los 12 meses cuando la pérdida renal fue temprana (p: 0,042), y de la misma manera a los 12 meses, fueron más elevados los niveles de creatinina cuando el diagnóstico histopatológico fue Nefropatía por Poliomavirus Clase 3 (p: 0,01). DISCUSIÓN. La prevalencia de la nefropatía se mantuvo por debajo del 10% reportado a nivel global, la creatinina empeoró en pacientes con pérdida temprana del injerto renal y con una clase patológica avanzada, hecho reportado en la fisiopatología de la enfermedad. CONCLUSIÓN. La pérdida del injerto renal temprano presentó una creatinina más alta que la tardía. Es recomendable un tamizaje adecuado para la detección temprana del virus BK siendo crucial para prevenir el deterioro de la función renal y limitar la posterior pérdida del injerto.

INTRODUCTION: BK polyomavirus nephropathy is emerging as a significant concern in kidney transplantation, as it contributes to the early loss of renal grafts. OBJECTIVE: The aim of this study was to clinically characterize renal transplant recipients with BK polyomavirus nephropathy. MATERIALS AND METHODS: An observational and descriptive study was conducted at Carlos Andrade Marín Specialties Hospital during the period of 2013 to 2022. An anonymized database comprising 479 renal transplant patients was utilized. Among these, 37 patients, constituting 7.7%, were identified with BK polyomavirus nephropathy. Data analysis was performed using the statistical program SPSS v26®. RESULTS: The study population was predominantly composed of male patients (56.8%) with a mean age of 48.2 years. Deceased donors accounted for the majority (94.5%) of cases. The primary approach for managing BK polyomavirus nephropathy involved transitioning from mycophenolate sodium to everolimus, alongside maintaining a regimen of 50% tacrolimus and 40.5% prednisone. When assessing changes in creatinine values, the highest levels were observed at 12 months, coinciding with early renal loss (p: 0.042). Similarly, at the 12-month mark, elevated creatinine levels were associated with a histopathological diagnosis of Polyomavirus nephropathy Class 3 (p: 0.01). DISCUSSION: The prevalence of nephropathy remained below the globally reported threshold of 10%. Creatinine levels worsened in patients experiencing early graft loss and an advanced pathological classification, aligning with established disease pathophysiology. CONCLUSION: Early renal graft loss was associated with higher creatinine levels compared to delayed loss. Adequate screening for early detection of BK virus is recommended, as it plays a crucial role in preventing renal function deterioration and limiting subsequent graft loss.

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Siponimod es un medicamento inmunosupresor selectivo, desarrollado como la primera terapia oral para la esclerosis múltiple secundaria progresiva activa. Este medicamento actúa modulando el receptor de esfingosina 1 fosfato (S1P), como antagonista de S1P1 y S1P5, evitando así la salida de linfocitos desde los nódulos linfáticos y previniendo procesos inflamatorios en el Sistema Nervioso Central que desencadenan una desmielinización. Existe amplio conocimiento científico respecto a que la administración del medicamento a pacientes va a depender de sus características farmacogenéticas, por lo que la FDA recomienda fuertemente realizar un estudio de genotipificación de la enzima que metaboliza siponimod, CYP2C9, cuyas variantes genéticas *2 y *3 clasifican a pacientes como metabolizadores pobres, extensivos o rápidos. Para pacientes homocigotos de CYP2C9*3 siponimod está totalmente contraindicado. Adicionalmente, antes de su prescripción se debe realizar un electrocardiograma, evaluaciones del estado de anticuerpos, oftálmica, estado de vacunación contra varicela y recuento de linfocitos periféricos, ya que el efecto del medicamento es dependiente de la dosis administrada, por lo que se realiza un proceso de titulación en dosis desde los 0,25mg hasta los 2 mg. El protocolo farmacoterapéutico de siponimod es reflejo fidedigno de la utilidad de la farmacogenética en la medicina personalizada..

Siponimod is a selective immunosuppressive medication, developed as the first oral therapy for active secondary progressive multiple sclerosis. This medication acts by modulating the sphingosine 1 phosphate (S1P) receptor, as an antagonist of S1P1 and S1P5, thus preventing the egress of lymphocytes from lymph nodes and preventing inflammatory processes in the Central Nervous System that trigger demyelination. There is extensive scientific knowledge regarding the administration of the medication to patients, which will depend on their pharmacogenetic characteristics. Therefore, the FDA strongly recommends conducting a genotyping study of the enzyme that metabolizes siponimod, CYP2C9, whose genetic variants *2 and *3 classify patients as poor, extensive, or rapid metabolizers. Siponimod is completely contraindicated for patients who are homozygous for CYP2C9*3. Additionally, before prescribing it, an electrocardiogram, assessments of antibody status, ophthalmic evaluation, varicella vaccination status, and peripheral lymphocyte count should be conducted, as the medication's effect is dose-dependent. Therefore, a titration process is carried out starting from 0.25mg up to 2 mg. The pharmacotherapeutic protocol of siponimod is a reliable reflection of the utility of pharmacogenetics in personalized medicine.

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INTRODUCCIÓN. La sepsis es un estado de disfunción multisistémica, que se produce por una respuesta desregulada del huésped a la infección. Diversos factores influyen en la gravedad, manifestaciones clínicas y progresión de la sepsis, tales como, heterogeneidad inmunológica y regulación dinámica de las vías de señalización celular. La evolución de los pacientes depende del tratamiento oportuno, las escalas de puntuación clínica permiten saber la mortalidad estimada. OBJETIVO. Evaluar la mortalidad en la unidad de cuidados intensivos; establecer el manejo y la utilidad de aplicar paquetes de medidas o "bundlers" para evitar la progresión a disfunción, fallo multiorgánico y muerte. METODOLOGÍA. Modalidad de investigación tipo revisión sistemática. Se realizó una búsqueda bibliográfica en bases de datos como Google académico, Mendeley, ScienceDirect, Pubmed, revistas como New England Journal Medicine, Critical Care, Journal of the American Medical Association, British Medical Journal. Se obtuvo las guías "Sobreviviendo a la sepsis" actualización 2021, 3 guías internacionales, 10 estudios observacionales, 2 estudios multicéntricos, 5 ensayos aleatorizados, 6 revisiones sistémicas, 5 metaanálisis, 1 reporte de caso clínico, 4 artículos con opiniones de expertos y actualizaciones con el tema mortalidad de la sepsis en UCI con un total de 36 artículos científicos. RESULTADOS. La mortalidad de la sepsis en la unidad de cuidados intensivos, fue menor en el hospital oncológico de Guayaquil, seguido de Australia, Alemania, Quito, Francia, Estados Unidos de Norteamérica y Vietnan, La mortalidad más alta se observa en pacientes con enfermedades del tejido conectivo. DISCUSIÓN. La aplicación de los paquetes de medidas o "bundlers" en la sepsis, se asocia con una mejor supervivencia y menores días de estancia hospitalaria. CONCLUSIÓN. Las escalas SOFA, APACHE II y SAPS II ayudan a predecir la mortalidad de forma eficiente, en la detección y el tratamiento temprano en pacientes con enfermedades agudas y de alto riesgo.

INTRODUCTION. Sepsis is a state of multisystem dysfunction, which is caused by a dysregulated host response to infection. Several factors influence the severity, clinical manifestations and progression of sepsis, such as immunological heterogeneity and dynamic regulation of cell signaling pathways. The evolution of patients depends on timely treatment, clinical scoring scales allow to know the estimated mortality. OBJECTIVE. To evaluate mortality in the intensive care unit; to establish the management and usefulness of applying bundlers to prevent progression to dysfunction, multiorgan failure and death. METHODOLOGY. Systematic review type research modality. A bibliographic search was carried out in databases such as Google Scholar, Mendeley, ScienceDirect, Pubmed, journals such as New England Journal Medicine, Critical Care, Journal of the American Medical Association, British Medical Journal. We obtained the guidelines "Surviving Sepsis" update 2021, 3 international guidelines, 10 observational studies, 2 multicenter studies, 5 randomized trials, 6 systemic reviews, 5 meta-analyses, 1 clinical case report, 4 articles with expert opinions and updates on the subject of sepsis mortality in ICU with a total of 36 scientific articles. RESULTS. The mortality of sepsis in the intensive care unit, was lower in the oncological hospital of Guayaquil, followed by Australia, Germany, Quito, France, United States of America and Vietnam, The highest mortality is observed in patients with connective tissue diseases. DISCUSSION. The application of bundlers in sepsis is associated with better survival and shorter days of hospital stay. CONCLUSIONS. The SOFA, APACHE II and SAPS II scales help to predict mortality efficiently in the early detection and treatment of patients with acute and high-risk disease.

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INTRODUCCIÓN. La enfermedad renal crónica es definida como la pérdida progresiva, permanente e irreversible de la función renal, uno de los tratamientos es el trasplante renal el mismo que aumenta la calidad de vida de los pacientes que presentan esta patología, sin embargo, a pesar de ser uno de las mejores terapias no está exento de complicaciones especialmente las que se presentan posterior al acto quirúrgico ya que afectan al buen funcionamiento del injerto y afecta la supervivencia del mismo. OBJETIVO. Determinar la prevalencia de complicaciones clínicas y quirúrgicas en el postrasplante renal inmediato con el fin de identificar las principales complicaciones que ocasionan mayor deterioro en la función renal a corto plazo. MATERIAL Y MÉTODOS. Estudio Observacional descriptivo transversal, de pacientes trasplantados que se encuentran en seguimiento desde enero del 2015 hasta diciembre del 2018 en el servicio de Trasplante renal del Hospital de Especialidades Carlos Andrade Marín. La muestra será los 211 pacientes trasplantados de donante cadavérico. Los análisis se realizaron con el paquete estadístico IBM SPSS versión 25, para lo cual se empleó estadísticas descriptivas, utilizando tablas y representando los valores absolutos y relativos de las variables cualitativas, así como medidas de tendencia central y de variabilidad para las variables cuantitativas. RESULTADOS. Se estudiaron 193 pacientes trasplantados de los cuales el 49.66% tuvieron complicaciones, de los mismos el 33.16% fueron complicaciones clínicas y 16,5% complicaciones quirúrgicas; de las clínicas la infección de tracto urinario fueron las más prevalentes con 15%, seguida por el rechazo agudo 6,7%, las infecciones por virus poliomavirus BK fueron un porcentaje de 6,2%, la necrosis tubular aguda el 3,16% terminando con el rechazo hiperagudo en el 1,5% y la toxicidad por calcineurínicos 1,04%. Mientras tanto las complicaciones quirúrgicas las urológicas son las más prevalentes 8,8% seguida por las colecciones liquidas con el 6,74% finalmente la trombosis vascular con el 1,04%. CONCLUSIONES. Las complicaciones más prevalentes son las clínicas vs las quirúrgicas, afectando de igual forma la función renal al año sin diferencia estadísticamente significativa.

INTRODUCTION. Chronic kidney disease is defined as the progressive, permanent and irreversible loss of renal function, one of the treatments is renal transplantation, which increases the quality of life of patients with this pathology, however, despite being one of the best therapies, it is not free of complications, especially those that occur after surgery, since they affect the proper functioning of the graft and affect its survival. OBJECTIVE. To determine the prevalence of clinical and surgical complications in immediate post-renal transplantation in order to identify the main complications that cause greater deterioration in short-term renal function. MATERIAL AND METHODS. Cross-sectional descriptive observational study, of transplanted patients under follow-up from January 2015 to December 2018 in the Renal Transplant service of the Hospital de Especialidades Carlos Andrade Marín. The sample will be the 211 cadaveric donor transplanted patients. The analyses were performed with the IBM SPSS version 25 statistical package, for which descriptive statistics were used, using tables and representing the absolute and relative values of qualitative variables, as well as measures of central tendency and variability for quantitative variables. RESULTS. We studied 193 transplanted patients of whom 49.66% had complications, of which 33. Of the clinical complications, urinary tract infection was the most prevalent with 15%, followed by acute rejection 6.7%, polyomavirus BK infections were 6.2%, acute tubular necrosis 3.16%, ending with hyperacute rejection in 1.5% and calcineurin toxicity 1.04%. Meanwhile, urological surgical complications are the most prevalent 8.8% followed by liquid collections with 6.74% and finally vascular thrombosis with 1.04%. CONCLUSIONS. The most prevalent complications are clinical vs. surgical, affecting renal function at one year with no statistically significant difference.

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Neuropsychiatric syndromes in systemic lupus erythematosus (SLE) are one of the many clinical manifestations in which this pathology presents. They have a wide range of prevalence, from 37- 95% due to factors like absence of standardized definitions and non-nespecific clinical manifestations. Physiopathology is mediated by autoimmune mechanisms commonly differentiated in ischemic and inflammatory; there is a clear relationship between the pathologic pathway and the neuropsychiatric manifestation. Moreover, the blood-brain barrier plays a key role, since an alteration of the permeability allows the pass of autoantibodies to the cerebrospinal fluid. There are 19 neuropsychiatric syndromes described which include both diffuse and focal manifestations. The diagnosis must be of exclusion in sights of the more prevalent, severe and potentially deadly etiologies of the neuropsychiatric manifestations, being indispensable to conduct a full study of the patient. The therapyfocuses on symptomatic treatment for each manifestation. Immunotherapy and antithrombotic treatments should be prescripted depending on the underlying pathophysiological mechanism; however, to uncover the predominant pathological route remains a challenge. Future studies should be focused in a better understanding of the physiopathological routes in order to develop standardized diagnosis criteria and optimize an early treatment. This would have a major impact in the life of patients suffering from neuropsychiatric manifestations of SLE, whose late diagnosis is linked with greater organic damage and a poorer quality of life.

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BACKGROUND: Ototoxicity is a side effect of drugs and medications that usually leads to bilateral and symmetric sensorineural hearing loss that commonly affects the high-frequency range initially, with or preceded by tinnitus. Possible ototoxic side effects of calcineurin inhibitor immunosuppressants have been suggested, but this remains unclear. Therefore, this study aims to evaluate audiological changes in patients undergoing transplantation receiving immunosuppressive treatment with calcineurin inhibitors. METHODS: Prospective cohort study. Adult patients undergoing liver or kidney transplantation treated with calcineurin inhibitors were included. Pure-tone audiometry, distortion product otoacoustic emissions, and the Tinnitus Handicap Inventory questionnaire were completed at baseline, one, three, and six months after transplantation. Hearing thresholds were compared and correlated with plasma concentrations of calcineurin inhibitors. RESULTS: Seventeen patients were included, 59% males, with a median age of 54.7 years (29-68 years). Twelve patients underwent liver transplantation, four underwent kidney transplantation, and one patient underwent both. The medianfollow-up was 5.8 months (4-8 months). Significant pure-tone average shifts were observed in two patients. Both cases presented fluctuations in their hearing levels, which were not bilateral or symmetrical and affected the higher frequencies. All patients received tacrolimus within the therapeutic range during the follow-up period. Three different patients exceeded the expected range once; however, they were rapidly corrected and did not correlate with any changes in hearing. CONCLUSIONS: It appears that tacrolimus does not cause hearing loss when levels are within the therapeutic range for a follow-up period of six months post-transplantation.

INTRODUCCIÓN: La ototoxicidad corresponde a un efecto secundario a agentes terapéuticos que se manifiesta como hipoacusia sensorioneural bilateral simétrica de frecuencias agudas. Se postulan posibles efectos ototóxicos de los inmunosupresores inhibidores de la calcineurina, pero hasta la fecha es aún incierto. El objetivo de este estudio fue evaluar los cambios audiológicos en pacientes trasplantados en tratamiento inmunosupresor con inhibidores de calcineurina. MATERIAL Y MÉTODO: Cohorte prospectiva. Se incluyeron pacientes adultos sometidos a trasplante hepático o renal tratados con inhibidores de calcineurina. Se realizó una evaluación otorrinolaringo-lógica pre-trasplante con audiometría tonal, emisiones otoacústicas por producto de distorsión y cuestionario Tinnitus Handicap Inventory. Se realizó una evaluación audiológica de seguimiento uno, tres y seis meses después del trasplante. Se compararon los umbrales auditivos antes y después del inicio del tratamiento inmunosupresor y se correlacionaron con las concentraciones plasmáticas de IC. RESULTADOS: Se incluyeron 17 pacientes, 59% hombres, con una mediana de edad de 54,7 años. La mediana de seguimiento fue 5,8 meses. Se observaron cambios en el promedio tonal puro en dos pacientes, los cuales no seguían un patrón audiométrico sugerente de ototoxicidad. Todos los pacientes recibieron Tacrolimus dentro del rango terapéutico durante el seguimiento. Tres pacientes diferentes excedieron el rango esperado una vez sin embargo, se corrigieron rápidamente y no se correlacionaron con cambios auditivos, puntaje de tinnitus o emisiones otoacústicas. DISCUSIÓN: Impresiona que Tacrolimus no se asocia a hipoacusia cuando los niveles están en rango terapéutico durante un período de seguimiento de seis meses post trasplante.

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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.

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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.

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OBJECTIVE@#To evaluate the efficacy, safety and relapse of cyclosporine A (CsA) and CsA combined with corticosteroid (CS) as the frontline therapy for patients with newly diagnosed acquired pure red cell aplasia (aPRCA).@*METHODS@#The clinical features, treatment responses, relapses and clinical outcomes of patients with newly diagnosed aPRCA in Peking Union Medical College Hospital (PUMCH) from January 2015 to May 2020 were analyzed retrospectively. All the enrolled patients had been treated with either CsA or CsA+CS for at least 6 months and had been followed up for at least 12 months, with complete clinical data and consent forms.@*RESULTS@#96 patients including 72 treated with CsA and 24 treated with CsA+CS were enrolled. With comparable baseline characteristics and follow-up periods, patients treated with CsA or with CsA+CS had similar overall response rates (ORRs) and complete response rates (CRRs) at the 3rd, 6th and 12th month and at the end of follow-up (P>0.05). Meanwhile, no significant difference was found between the two groups in the optimal ORR, optimal CRR, time to response or time to complete response. CsA+CS and CsA groups had similar adverse event (AE) rates, but CsA+CS group had higher CS-related infection rate (P <0.05). One patient in CsA+CS group died of multiple infections. As for the relapse, the two groups had compatible relapse rates at different time points, time to relapse, overall relapse rate and relapse-free survival (P>0.05). CsA exposure time, rather than different therapy regimens, was the only influence factor for either ORR or relapse rate (P <0.05).@*CONCLUSION@#CsA monotherapy has similar efficacy, AE rate and relapse rate as compared with CsA+CS for patients with newly diagnosed aPRCA, and shows less CS-related AEs such as infection.

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Calcineurin inhibitors (CNI), including oral cyclosporin A and tacrolimus, are intensive immunosuppressants that are extensively used in the treatment of rheumatic and immunologic diseases in China. CNI selectively inhibit the activation and proliferation of T lymphocytes and the transcription of cytokines [such as tumor necrosis factor-α, interleukin (IL)-6, and IL-17] through inhibiting the activation of calcineurin in cells and reducing the release of IL-2. To standardize the use of CNI in the field of rheumatic and immunologic diseases, this consensus statement was developed by the National Clinical Research Center for Dermatologic and Immunologic Diseases (Peking Union Medical College Hospital), in conjunction with the Chinese Association of Rheumatology and Immunology Physicians, the Chinese Research Hospital Association, the Rheumatology and Immunology Professional Committee, and the Chinese Association of Rehabilitation Medicine. The 2011 Oxford Centre for Evidence-Based Medicine Levels of Evidence was used to rate the quality of the evidence and the strength of the recommendations, and the RIGHT (Reporting Items for practice Guidelines in HealThcare) checklist was followed to report the consensus. The consensus offers recommendations addressing nine clinical challenges to Chinese clinicians. The primary objective of this consensus is to deliver scientific and detailed guidance on CNI for Chinese clinicians, and to improve the quality of patient-centered medical services.