Manejo de la inmunosupresión en pacientes trasplantados de riñón con COVID19. Estudio multicéntrico nacional derivado del registro COVID de la Sociedad Española de Nefrología / Management of immunosuppressive therapy in kidney transplant recipients with COVID-19. A multicentre national study derived from the Spanish Society of Nephrology. COVID registry

Introducción: La infección por SARS-CoV2 ha impactado de forma importante en los pacientes con trasplante renal causando una elevada mortalidad en los primeros meses de la pandemia. La reducción intencionada de la inmunosupresión se ha postulado como uno de los pilares en el manejo de la infección ante la falta de un tratamiento antiviral dirigido. Esta se ha modificado de acuerdo con la situación clínica de los pacientes, y su efecto sobre la función renal o los anticuerpos anti-HLA a medio plazo no ha sido evaluado. Objetivos: Evaluar los cambios de inmunosupresión realizados durante la infección por SARS-CoV2, así como la función renal y los anticuerpos anti-HLA de los pacientes trasplantados de riñón a los 6 meses del diagnóstico de COVID19. Material y métodos: Estudio retrospectivo, multicéntrico nacional (30 centros) de pacientes trasplantados de riñón con COVID19 desde el 01/02/20 al 31/12/20. Se recogieron las variables de la historia clínica y se incluyeron en una base de datos anonimizada. Se utilizó el programa estadístico SPSS para el análisis de resultados. (AU)

Introduction: SARS-CoV-2 infection has had a major impact on renal transplant patients with a high mortality in the first months of the pandemic. Intentional reduction of immunosuppressive therapy has been postulated as one of the cornerstone in the management of the infection in the absence of targeted antiviral treatment. This has been modified according to the patient's clinical situation and its effect on renal function or anti-HLA antibodies in the medium term has not been evaluated. Objectives: Evaluate the management of immunosuppressive therapy made during SARS-CoV-2 infection, as well as renal function and anti-HLA antibodies in kidney transplant patients 6 months after COVID-19 diagnosis. Material and methods: Retrospective, national multicentre, retrospective study (30 centres) of kidney transplant recipients with COVID19 from 01/02/20 to 31/12/20. Clinical variables were collected from medical records and included in an anonymised database. SPSS statistical software was used for data analysis. (AU)

Immunotherapy combined with radiotherapy to reverse immunosuppression in microsatellite stable colorectal cancer

In recent years, the exploration of immune checkpoint inhibitors (ICIs) has resulted in substantial progress and has changed the pattern of cancer treatment. ICIs have revolutionized the treatment landscape of microsatellite instable colorectal cancer while the efficacy is very limited in patients with microsatellite stable colorectal cancer. Therefore, sensitizing MSS CRC to immunotherapy is a major challenge in the field of CRC immunotherapy. Immunotherapy-based combination therapy is an effective strategy. This review of radiotherapy (RT) as a local treatment has dramatically changed in recent years, and it is now widely accepted that RT can deeply reshape the tumor environment by modulating the immune response. Such evidence gives a strong rationale for the synergism of radiotherapy and immunotherapy, introducing the era of ‘immunoradiotherapy’. How to give full play to the synergistic effect of radiotherapy and immunotherapy to improve the therapeutic effect of MSS CRC and bring good prognosis is a hot problem to be solved in the field of cancer treatment.This article reviews the development of CRC immunotherapy, the immune resistance mechanism of MSS CRC, and the impact and potential value of immunotherapy combined with radiotherapy on the immune environment of CRC (AU)

Interplay between tumor-derived factors and tumor-associated neutrophils: opportunities for therapeutic interventions in cancer

Neutrophils have emerged as important players in the tumor microenvironment, largely attributed to their plasticity and heterogeneity. Evidence accumulated thus far indicates that neutrophils signaled by external cues can promote tumor progression via several mechanisms. Hence, in our quest to target tumor-associated neutrophils to improve treatment, understanding the mechanisms by which tumor-derived factors regulate neutrophils to gain pro-tumor functions and the feedback loop by which these neutrophils promote tumor progression is very crucial. Herein, we review the published data on how tumor-derived factors alter neutrophils phenotype to promote tumor progression with particular emphasis on immunosuppression, autophagy, angiogenesis, tumor proliferation, metastasis, and therapeutic resistance. These deeper insights could provide a wider view and novel therapeutic approach to neutrophil-targeted therapy in cancer (AU)

ENO1 promotes immunosuppression and tumor growth in pancreatic cancer

Background Pancreatic adenocarcinoma (PAAD) is a highly aggressive and malignant cancer type with the highest mortality rate of all major cancers. However, the molecular and tumor immune escape mechanism underlying pancreatic cancer remains largely unclear. α-enolase (ENO1) is a glycolytic enzyme reported to overexpress in a variety of cancer types. This study was undertaken to investigate the functional role and therapeutic potential of ENO1 in pancreatic cancer. Methods We examined the expression levels of ENO1 across a broad spectrum of cancer types from the TCGA database. ENO1-knockout (ENO1-KO) through CRISPR/CAS9 technology in a mouse pancreatic cancer cell line (PAN02) was used to analyze the role of ENO1 on proliferation and colony formation. Flow cytometry and RT-PCR were also applied to analyze T lymphocytes and relevant cytokines. Results In the present study, we identified that ENO1 promoted pancreatic cancer cell proliferation. Our bioinformatics data indicated that ENO1 was significantly overexpressed in pancreatic cancer cell lines and tissues. Survival analyses revealed that ENO1 overexpression implicated poor survival of PAAD patients. Knockout of ENO1 expression repressed the ability of proliferation and colony formation in PAN02. In addition, ENO1-KO significantly decreased tumor growth in mouse models. Further flow cytometry and RT-PCR analysis revealed that ENO1-KO modulates the tumor microenvironment (TME), especially in suppressed Treg cells and inducing anti-tumor cytokine responses. Conclusions Taken together, our data showed that ENO1 was an oncogenic biomarker and might serve as a promising target for immunotherapy of pancreatic cancer (AU)

Opportunistic infections as a cause of death in patients with autoimmune diseases: An autopsy-based study / Infecciones oportunistas como causa de muerte en pacientes con enfermedades autoinmunes: estudio basado en autopsias

Background: Infections are an important cause of mortality in patients with autoimmune diseases and opportunistic infections account for a large percentage of these cases. It is often a clinical challenge to find a balance between immunosuppressive therapy and the risk of developing an infectious process. Methods: A retrospective, descriptive study of autopsy reports. Results: 15 patients with a premortem diagnosis of autoimmune disease were included. All patients died due to an opportunistic infection. The most commonly reported infection was tuberculosis, followed by invasive fungal infections. Conclusions: The most prevalent pathogens were found in our autopsy-based study of patients with autoimmune diseases and opportunistic infections. Prevention and early detection strategies are vital in order to reach a correct diagnosis and begin the appropriate treatment as soon as possible.(AU)

Antecedentes: Las infecciones son una causa importante de mortalidad en pacientes con enfermedades autoinmunes. Las infecciones oportunistas engloban un gran porcentaje de estos casos. Encontrar un equilibrio entre la terapia inmunosupresora y el riesgo de desarrollar procesos infecciosos normalmente constituye un desafío clínico. Métodos: Estudio retrospectivo y descriptivo de informes de autopsias. Resultados: Se incluyó a 15 pacientes con diagnóstico pre mortem de enfermedad autoinmune. Todos los pacientes fallecieron debido a infecciones oportunistas. La infección más frecuentemente reportada fue la tuberculosis, seguida de infecciones fúngicas invasivas. Conclusiones: En este estudio basado en autopsias, realizado en pacientes con enfermedades autoinmunes e infecciones oportunistas, se recogieron los patógenos más prevalentes. Es clave establecer estrategias de prevención y detección temprana en estos grupos de pacientes para realizar un diagnóstico precoz e introducir con prontitud el tratamiento adecuado.(AU)

Tuberculosis screening after detection of a case in a paediatric haemato-oncology unit in a low prevalence country / Cribado de tuberculosis tras la detección de un caso en una unidad de hematooncología pediátrica en un país con baja prevalencia

Background: There are no guidelines to screen haemato-oncologic children when a tuberculosis (TB) outbreak is suspected. Methods: After exposition to an adult with active TB, children exposed from a haemato-oncology unit were screened according to immunosuppression status and time of exposure. Until an evaluation after 8–12 weeks from last exposure, isoniazid was indicated to those with negative initial work-up. Results: After 210 interventions, we detected a case of pulmonary TB, and another with latent TB infection. Pulmonary findings and treatment approach were challenging in some patients. Conclusions: The TB screening of oncologic children required a multidisciplinary approach, and clinicians managed challenging situations.(AU)

Antecedentes: No existen pautas para el cribado de niños hematooncológicos cuando se sospecha de un brote de tuberculosis (TB). Métodos: Después de la exposición a un adulto con TB activa, se evaluó a los niños expuestos de una unidad de hematooncología según el estado de inmunosupresión y el tiempo de exposición. Hasta una evaluación después de ocho a12 semanas desde la última exposición, se indicó isoniazida para aquellos con un proceso inicial negativo. Resultados: Tras 210 intervenciones se detectó un caso de tuberculosis pulmonar y otro con infección por TB latente. Los hallazgos pulmonares y el método de tratamiento fueron un desafío en algunos pacientes. Conclusiones: El cribado de TB en niños oncológicos requirió un método multidisciplinario y los médicos manejaron situaciones complejas.(AU)

Respuesta inmunológica en cirugía del cáncer de mama. Estudio comparativo y prospectivo de diferentes técnicas anestésicas / Immune response in breast cancer surgery. A comparative and prospective study of different anesthetic techniques

Introducción: El principal motivo de la alta mortalidad en el cáncer de mama es la recurrencia local y las metástasis, siendo la cirugía la primera opción terapéutica. La técnica anestésica utilizada en quirófano puede modificar la respuesta inmunológica del paciente. Métodos: Estudio prospectivo, comparativo y no aleatorizado en pacientes intervenidos de cáncer de mama en el Hospital Universitario de Getafe (Madrid) tras la aprobación del Comité Ético del Hospital.Dividimos a los pacientes en dos grupos: grupo A, que recibió anestesia general con propofol y fármacos opiáceos; grupo B, en el que además de la anestesia general, se realizaron tres bloqueos interfasciales (Pec I, Pec II y BRILMA) en todos los pacientes. Se obtuvieron tres muestras sanguíneas: 1) antes de la inducción anestésica; 2) 2h después de finalizar la cirugía y 3) 24-48h posquirúrgicas. En cada muestra, se analizaron el número de leucocitos, células CD3, CD4 y CD8, así como las células natural killer (NK). Resultados: Se incluyeron en el estudio un total de 103 pacientes; 59 (grupo A) recibieron anestesia general y 54 (grupo B) anestesia general y bloqueos interfasciales. Según las características basales, la edad fue significativamente superior en las pacientes que recibieron anestesia general. La mastectomía se realizó con más frecuencia en el grupo que recibió bloqueos interfasciales. Observamos que después de la cirugía hay un aumento en el número de leucocitos pero regresa a los niveles basales a las 48h, comportamiento que se repite a nivel inmunológico: disminuye después de la cirugía pero vuelve a niveles previos a las 48h de la cirugía. Los grupos A y B presentan resultados similares en el resto de parámetros estudiados, al igual que los subgrupos según los receptores hormonales (HER+, PR y/o ER+).(AU)

Introduction: The main reason for high mortality in breast cancer is local recurrence and metastasis, despite surgery as the first therapeutic option. The anesthesia used in the operation room can determine the immune response. Methods: A prospective, comparative and non-randomized study in patients undergoing breast cancer surgery was conducted in our hospital after obtaining approval from the Hospital's Institutional Review Board. Patients were divided in two groups: Group A received general anesthesia with propofol and opioids. Group B, in addition to general anesthesia, three interfascial blocks (Pec I, Pec II and BRILMA) were performed in all patients. Three blood samples were taken 1) previous anesthetic induction; 2) two hours after the end of the surgery and 3) 24-48hours after surgery. Leukocytes, CD3, CD4, CD8 and Natural Killer cells were determined at each time. Results: 103 patients were included. 59 (group A) received general anesthesia and 54 (group B) general anesthesia and interfascial blocks. Regarding baseline characteristics, age was significantly higher in the group that received general anesthesia and mastectomy was more frequent in the group that received interfascial blocks.We observed after surgery an increase in leukocytes level that returns close to baseline levels. On the other hand, a reduction in the immune response was observed that also returns to the previous level 48hours after surgery. Group A and B get similar results and also subgroups of hormonal receptors (HER+, PR and/or ER+). Conclusions: Interfascial blocks in chest wall added to general anesthesia in breast cancer surgery has not shown a significant difference in the inflammatory response or immunological depression compared to general anesthesia as the only anesthetic technique. It seems to trend less immunological depression in the interfascial block group.(AU)

SEOM clinical guidelines for the prophylaxis of infectious diseases in cancer patients (2021)

Infections are still a major cause of morbi-mortality in patients with cancer. Some of these infections are preventable through specific measures, such as vaccination or prophylaxis. This guideline aims to summarize the evidence and recommendations for the prevention of infections in cancer patients, devoting special attention to the most prevalent preventable infectious disease. All the evidences will be graded according to The Infectious Diseases Society of America grading system.

Penfigoide ocular cicatricial: ¿metotrexato como tratamiento de inicio? / Ocular Cicatricial Pemphigoid: Methotrexate as an Initial Treatment?

Objetivo: Analizar los datos clínicos/epidemiológicos, el manejo y los tratamientos instaurados a pacientes con penfigoide ocular cicatricial en un Servicio de Reumatología. Material y métodos: Revisión de historias clínicas de pacientes con penfigoide ocular cicatricial derivados por oftalmología entre 2008 y 2019. Resultados: En nuestra serie de 27 pacientes, el 67% fue diagnosticado y derivado en los últimos 2 años. La mayoría en estadio 1 de Foster. El 18,5% presentó síndrome de Sjogren asociado, conllevando una evolución desfavorable. El 88,8% recibió metotrexato, el 74% lo utilizó en monoterapia y el 66% continuó el tratamiento hasta el final. El 18,5% debió combinar/rotar terapias, los fármacos utilizados fueron micofenolato, azatioprina, ciclofosfamida, sirolimus, rituximab. El 29% utilizó esteroides. Solo en 2 ojos progresó el estadio. No se registraron eventos adversos serios y el 37% presentó eventos adversos leves. Conclusión: El inicio temprano de la terapia inmunosupresora es fundamental, siendo el metotrexato una buena alternativa como tratamiento de inicio según nuestra experiencia, debiendo escalar el tratamiento de acuerdo a la evolución.(AU)

Objective: To analyse the clinical / epidemiological data, the management and the treatments established in patients with ocular cicatricial pemphigoid in a Rheumatology Service. Material and methods: Review of clinical histories of patients with ocular cicatricial pemphigoid referred by ophthalmology between 2008 and 2019. Results: In our series of 27 patients, 67% were diagnosed and referred in the last 2 years. Most in Foster stage 1. Of the patients, 18.5% presented associated Sjogren's syndrome, with poor progression: 88.8% received Methotrexate, 74% used it as monotherapy and 66% continued with said treatment up to the end. Eighteen point five percent had to combine or rotate therapies, the drugs used were mycophenolate, azathioprine, cyclophosphamide, sirolimus, etanercept, rituximab: 29% used steroids. Only in 2 eyes was stage progression observed. There were no serious adverse events, and 37% had mild adverse events. Conclusion: Starting immunosuppressive therapy early is essential, methotrexate being a good initial alternative in our experience, and treatment must be escalated in line with disease progression.(AU)

Riesgo de infección asociado a los inhibidores de las quinasas Janus (JAK) y las terapias biológicas en enfermedad inflamatoria intestinal y artritis reumatoide. Estrategias de prevención / Risk of infection associated with Janus Kinase (JAK) inhibitors and biological therapies in inflammatory intestinal disease and rheumatoid arthritis. Prevention strategies

Los pacientes con ciertas enfermedades inflamatorias mediadas inmunológicamente, como la artritis reumatoide (AR) y la enfermedad inflamatoria intestinal (EII), presentan una mayor incidencia y gravedad de enfermedades infecciosas que la población general, asociadas especialmente a los tratamientos inmunosupresores que reciben.Dichos tratamientos actúan sobre el sistema inmunitario a través de diferentes mecanismos, causando diferentes grados de inmunosupresión y un riesgo variable dependiendo de si el patógeno es un virus, una bacteria o un hongo. Este artículo es una revisión de la bibliografía más relevante sobre el tema, seleccionada y debatida por un panel de expertos. El objetivo de este artículo es revisar el riesgo de infecciones en pacientes con EII y AR y las potenciales medidas preventivas.(AU)

Patients with certain immune-mediated inflammatory diseases, such as rheumatoid arthritis (RA) and inflammatory bowel disease (IBD), have an increased risk of severe infectious diseases than the general population, which are mainly associated with the immunosuppressive treatments that they receive.These treatments act on the immune system through different mechanisms, causing different degrees of immunosuppression and a variable risk depending on whether the pathogen is a virus, bacteria or fungus. This article reviews the most relevant literature on the subject, which was selected and discussed by a panel of experts. The aim of this article is to review the risk of infections in patients with IBD and RA, and the potential preventive measures.(AU)

SARS-CoV-2 (COVID-19) en pacientes con algún grado de inmunosupresión / SARS-CoV-2 (COVID-19) in Patients with some Degree of Immunosuppression

Antecedentes: No es claro si los pacientes con algún grado de inmunosupresión tienen peores desenlaces en la infección por SARS-CoV-2, en comparación con la población sana. Objetivo: Realizar una revisión narrativa de la información disponible sobre infección por SARS-CoV-2 en pacientes inmunosuprimidos, especialmente pacientes con cáncer, trasplantados, con patologías neurológicas, inmunodeficiencias primarias y secundarias. Resultados: Los pacientes con cáncer y tratamiento reciente del mismo (quimioterapia o cirugía) e infección por SARS-CoV-2 tienen mayor riesgo de peores desenlaces. En los pacientes trasplantados (renal, cardiaco y hepático), con patologías neurológicas (esclerosis múltiple [EM], neuromielitis óptica [NMODS], miastenia grave [MG]), inmunodeficiencias primarias e infección por virus de inmunodeficiencia humana (VIH) en asociación con uso de inmunosupresores, los estudios no han mostrado tendencia a peores desenlaces. Conclusión: Dada la poca evidencia con que contamos hasta el momento no es claro el comportamiento de la infección por SARS-CoV-2 en pacientes con inmunosupresión, pero los estudios actuales no han mostrado peores desenlaces en este tipo de pacientes, a excepción de los pacientes con cáncer.(AU)

Background: It is not clear whether patients with some degree of immunosuppression have worse outcomes in SARS-CoV-2 infection, compared to healthy people. Objective: To carry out a narrative review of the information available on infection by SARS-CoV-2 in immunosuppressed patients, especially patients with cancer, transplanted, neurological diseases, primary and secondary immunodeficiencies. Results: Patients with cancer and recent cancer treatment (chemotherapy or surgery) and SARS-CoV-2 infection have a higher risk of worse outcomes. In transplant patients (renal, cardiac and hepatic), with neurological pathologies (multiple sclerosis [MS], neuromyelitis optica [NMODS], myasthenia gravis [MG]), primary immunodeficiencies and infection with human immunodeficiency virus (HIV) in association with immunosuppressants, studies have shown no tendency for worse outcomes. Conclusion: Given the little evidence we have so far, the behaviour of SARS-CoV-2 infection in immunosuppressed patients is unclear, but current studies have not shown worse outcomes, except for patients with cancer.(AU)

Presentación atípica de nocardiosis pulmonar como pioneumotórax en un paciente en tratamiento con corticoides / Unusual presentation of pulmonary nocardiosis as pyopneumothorax in a patient under corticotherapy

Nocardiosis is a rare opportunistic infection caused by the bacteria Nocardia spp. It may present as a localized infection or as an invasive infection (pulmonary, central nervous system or disseminated). The authors describe a 76-year-old woman under corticotherapy for the last month because of a recent diagnosis of cryptogenic organising pneumonia. She presented to the emergency department with one-week evolution of pleuritic chest pain and shortness of breath. Chest radiograph showed a left hydropneumothorax. A chest tube was inserted, and the drained pleural effusion was purulent, compatible with a pyopneumothorax. The pleural fluid culture came positive for Nocardia cyriacigeorgica. Nocardiosis is a serious infection with non-specific presentation making its diagnosis a challenge. (AU)

Pneumocystis jirovecii en pacientes inmunocomprometidos con enfermedades reumáticas / Pneumocystis jirovecii in immunocompromised patients with rheumatic diseases

Las infecciones, entre ellas las oportunistas, constituyen una causa importante y frecuente de morbilidad y mortalidad en los pacientes con enfermedades reumáticas y autoinmunitarias sistémicas. La neumonía por Pneumocystis jirovecii, clásicamente considerada propia de pacientes con VIH, trasplantados o tratados con quimioterapia oncológica, aparece cada vez con mayor frecuencia en estos pacientes. Es por ello conveniente que los reumatólogos conozcan su mecanismo de producción, manifestaciones clínicas, tratamiento y profilaxis, aspectos todos ellos abordados en esta revisión.(AU)

Infections, including opportunistic infections, are a major and frequent cause of morbidity and mortality in patients with systemic autoimmune and rheumatic diseases. Pneumocystis jirovecii pneumonia, classically considered to be typical of HIV patients, transplanted patients or patients treated with oncological chemotherapy, is appearing increasingly frequently in these patients. Therefore, rheumatologists should know its mechanism of production, clinical manifestations, treatment and prophylaxis, all of which are addressed in this review.(AU)

Nen de 9 anys trasplantat cardíac I renal amb lesió dolorosa a l'engonal / No disponible

No disponible

Lesiones costrosas a estudio / Scabby injuries

No disponible

Pembrolizumab en pacientes en hemodiálisis ¿es seguro? / Pembrolizumab in hemodialysis patients. Is it safe?

No disponible

Inmunosupresión en el trasplante hepático en la era covid-19 / Liver transplant immunosuppression during the covid-19 pandemic

La infección por el virus SARS-CoV-2 ha producido una pandemia con graves consecuencias sobre nuestro sistema sanitario. Aunque el colectivo de pacientes trasplantados hepáticos representa solo una minoría de la población, los hepatólogos que seguimos a estos pacientes hemos intentado coordinar esfuerzos para protocolizar el manejo de la inmunosupresión durante la infección por SARS-CoV-2. Aunque no hay estudios sólidos que avalen recomendaciones generales, las experiencias con otras infecciones víricas (hepatitis C, citomegalovirus) sugieren que el manejo de la inmunosupresión sin micofenolato mofetilo ni inhibidores m-Tor (fármacos que además se asocian a leucopenia y linfopenia) puede resultar beneficiosa. Es importante además prestar atención a las posibles interacciones farmacológicas, especialmente en el caso de tacrolimus, con algunos de los tratamientos con efecto antiviral que se administran en el contexto de la covid-19 (lopinavir/ritonavir, azitromicina). Finalmente, deberá tenerse en cuenta el efecto inmunosupresor de fármacos inmunomoduladores (tocilizumab y similares) que se administran en pacientes con enfermedad pulmonar severa. En el artículo se revisan los mecanismos de actuación de los diferentes fármacos inmunosupresores, su potencial efecto sobre la infección por SARS-CoV-2 y se sugieren unas pautas en el manejo de la inmunosupresión

SARS-CoV-2 infection has produced a pandemic with serious consequences for our health care system. Although liver transplant patients represent only a minority of the population, the hepatologists who follow these patients have tried to coordinate efforts to produce a protocol the management of immunosuppression during SARS-CoV-2 infection. Although there are no solid studies to support general recommendations, experiences with other viral infections (hepatitis C, cytomegalovirus) suggest that management of immunosuppression without mycophenolate mofetil or m-Tor inhibitors (drugs that are also associated with leukopenia and lymphopenia) may be beneficial. It is also important to pay attention to possible drug interactions, especially in the case of tacrolimus, with some of the treatments with antiviral effect given in the context of COVID 19 (lopinavir/ritonavir, azithromycin). Finally, the immunosuppressive effect of immunomodulating drugs (tocilizumab and similar) administered to patients with severe lung disease should be taken into account. The mechanisms of action of the different immunosuppressive drugs are reviewed in this article, as well as their potential effect on SARS-CoV-2 infection, and suggests guidelines for the management of immunosuppression