Tools for a personalized tacrolimus dose adjustment in the follow-up of renal transplant recipients. Metabolizing phenotype according to CYP3A genetic polymorphisms versus concentration-dose ratio.

BACKGROUND AND JUSTIFICATION: The strategy of the concentration-dose (C/D) approach and the different profiles of tacrolimus (Tac) according to the cytochrome P450 polymorphisms (CYPs) focus on the metabolism of Tac and are proposed as tools for the follow-up of transplant patients. The objective of this study is to analyse both strategies to confirm whether the stratification of patients according to the pharmacokinetic behaviour of C/D corresponds to the classification according to their CYP3A4/5 cluster metabolizer profile. MATERIALS AND METHODS: 425 kidney transplant patients who received Tac as immunosuppressive treatment have been included. The concentration/dose ratio (C/D) was used to divide patients in terciles and classify them according to their Tac metabolism rate (fast, intermediate, and slow). Based on CYP3A4 and A5 polymorphisms, patients were classified into 3 metabolizer groups: fast (CYP3A5*1 carriers and CYP34A*1/*1), intermediate (CYP3A5*3/3 and CYP3A4*1/*1) and slow (CYP3A5*3/*3 and CYP3A4*22 carriers). RESULTS: When comparing patients included in each metabolizer group according to C/D ratio, 47% (65/139) of the fast metabolizers, 85% (125/146) of the intermediate and only 12% (17/140) of the slow also fitted in the homonym genotype group. Statistically lower Tac concentrations were observed in the fast metabolizers group and higher Tac concentrations in the slow metabolizers when compared with the intermediate group both in C/D ratio and polymorphisms criteria. High metabolizers required approximately 60% more Tac doses than intermediates throughout follow-up, while poor metabolizers required approximately 20% fewer doses than intermediates. Fast metabolizers classified by both criteria presented a higher percentage of times with sub-therapeutic blood Tac concentration values. CONCLUSION: Determination of the metabolizer phenotype according to CYP polymorphisms or the C/D ratio allows patients to be distinguished according to their exposure to Tac. Probably the combination of both classification criteria would be a good tool for managing Tac dosage for transplant patients.

Queratosis actínicas en pacientes trasplantados de órgano sólido: revisión de la literatura / Actinic Keratosis in Solid Organ Transplant Recipients: A Medical Literature Review

La inmunosupresión farmacológica de los pacientes trasplantados de órgano solido constituye un importante factor de riesgo tanto para la aparición de queratosis actínicas (QA) como para su progresión a carcinomas escamosos (CE). El tratamiento tanto de las lesiones clínicas como preclínicas en este grupo de pacientes es obligatorio debido a la elevada posibilidad de evolución a CE. Por otra parte, la prevención presenta también un papel importante que debemos tener en cuenta. Existen un gran número de estudios realizados en pacientes inmunocompetentes sobre el tratamiento y la prevención de QA, pero no en pacientes inmunosuprimidos. Esta revisión pretende resumir el conocimiento actual sobre los tratamientos y medidas de prevención de la QA en loas pacientes trasplantados de órgano sólido.(AU)

Pharmacological immunosuppression in solid organ transplant recipients is a significant risk factor in the occurrence of actinic keratosis (AK) and later progression into squamous cell carcinomas (SCC). Treating clinical and preclinical lesions is mandatory in this group of patients due to the high changes of progression into SCC. On the other hand, prevention of AK should be considered because it plays a crucial role.Several studies have been published on immunocompetent patients, as well as on the management and prevention of AK, but not on immunosuppressed patients.This review aims to summarize the current knowledge on the management and prevention measures of AK in solid organ transplant recipients.(AU)

[Translated article] Actinic Keratosis in Solid Organ Transplant Recipients: A Medical Literature Review / Queratosis actínicas en pacientes trasplantados de órgano sólido: revisión de la literatura

La inmunosupresión farmacológica de los pacientes trasplantados de órgano solido constituye un importante factor de riesgo tanto para la aparición de queratosis actínicas (QA) como para su progresión a carcinomas escamosos (CE). El tratamiento tanto de las lesiones clínicas como preclínicas en este grupo de pacientes es obligatorio debido a la elevada posibilidad de evolución a CE. Por otra parte, la prevención presenta también un papel importante que debemos tener en cuenta. Existen un gran número de estudios realizados en pacientes inmunocompetentes sobre el tratamiento y la prevención de QA, pero no en pacientes inmunosuprimidos. Esta revisión pretende resumir el conocimiento actual sobre los tratamientos y medidas de prevención de la QA en loas pacientes trasplantados de órgano sólido.(AU)

Pharmacological immunosuppression in solid organ transplant recipients is a significant risk factor in the occurrence of actinic keratosis (AK) and later progression into squamous cell carcinomas (SCC). Treating clinical and preclinical lesions is mandatory in this group of patients due to the high changes of progression into SCC. On the other hand, prevention of AK should be considered because it plays a crucial role.Several studies have been published on immunocompetent patients, as well as on the management and prevention of AK, but not on immunosuppressed patients.This review aims to summarize the current knowledge on the management and prevention measures of AK in solid organ transplant recipients.(AU)

Herramientas para un ajuste de dosis de tacrolimus más personalizado en el seguimiento de los pacientes con transplante renal. Fenotipo metabolizador según polimorfismos genéticos del CYP3A vs. el cociente concentración-dosis / Tools for a personalized tacrolimus dose adjustment in the follow-up of renal transplant recipients: Metabolizing phenotype according to CYP3A genetic polymorphisms versus concentration–dose ratio

Antecedentes y justificación: La estrategia de la aproximación concentración-dosis (C/D) y los distintos perfiles del tacrolimus (Tac), según los polimorfismos del citocromo P450 (CYPs) se centran en el metabolismo de Tac y se plantean como herramientas para el seguimiento de los pacientes trasplantados. El objetivo de este estudio es comparar la exposición al Tac analizado según ambas estrategias. Materiales y métodos: Se han incluido 425 pacientes trasplantados renales. El cálculo del cociente concentración Tac/dosis (C/D) permitió dividir la población en terciles y clasificar los pacientes según su tasa de metabolismo del Tac en tres grupos (rápida, intermedia y lenta). Con base en los polimorfismos del CYP3A4 y A5, los pacientes se agruparon en metabolizadores rápidos (portadores del CYP3A5*1 y CYP34A *1/*1), intermedios (CYP3A5*3/3 y CYP3A4*1/*1) y lentos (CYP3A5 *3/*3 y portadores del CYP3A4*22). Resultados: Al comparar los pacientes de cada grupo metabolizador según los dos criterios, coincidieron 47% (65/139) de los metabolizadores rápidos, 85% (125/146) de los intermedios y solo 12% (17/140) de los lentos. Se observaron concentraciones de Tac estadísticamente menores en los metabolizadores rápidos y concentraciones mayores en los lentos, comparándolos con el grupo intermedio según el cociente C/D o según polimorfismos. Los metabolizadores rápidos requirieron alrededor de 60% más de dosis de Tac que los intermedios a lo largo del seguimiento, mientras que los lentos aproximadamente 20% menos de dosis que los intermedios. Los metabolizadores rápidos clasificados por ambos criterios presentan un porcentaje mayor de veces con valores de concentración de Tac en sangre infraterapéuticos... (AU)

Background and justification: The strategy of the concentration–dose (C/D) approach and the different profiles of tacrolimus (Tac) according to the cytochrome P450 polymorphisms (CYPs) focus on the metabolism of Tac and are proposed as tools for the follow-up of transplant patients. The objective of this study is to analyse both strategies to confirm whether the stratification of patients according to the pharmacokinetic behaviour of C/D corresponds to the classification according to their CYP3A4/5 cluster metabolizer profile. Materials and methods: Four hundred and twenty-five kidney transplant patients who received Tac as immunosuppressive treatment have been included. The concentration/dose ratio (C/D) was used to divided patients in terciles and classify them according to their Tac metabolism rate (fast, intermediate, and slow). Based on CYP3A4 and A5 polymorphisms, patients were classified into three metabolizer groups: fast (CYP3A5*1 and CYP34A*1/*1 carriers), intermediate (CYP3A5*3/3 and CYP3A4*1/*1) and slow (CYP3A5*3/*3 and CYP3A4*22 carriers). Results: When comparing patients included in each metabolizer group according to C/D ratio, 47% (65/139) of the fast metabolizers, 85% (125/146) of the intermediate and only 12% (17/140) of the slow also fitted in the homonym genotype group. Statistically lower Tac concentrations were observed in the fast metabolizers group and higher Tac concentrations in the slow metabolizers when compared with the intermediate group both in C/D ratio and polymorphisms criteria. High metabolizers required approximately 60% more Tac doses than intermediates throughout follow-up, while poor metabolizers required approximately 20% fewer doses than intermediates. Fast metabolizers classified by both criteria presented a higher percentage of times with sub-therapeutic blood Tac concentration values... (AU)

[Translated article] Actinic Keratosis in Solid Organ Transplant Recipients: A Medical Literature Review.

Pharmacological immunosuppression in solid organ transplant recipients is a significant risk factor in the occurrence of actinic keratosis (AK) and later progression into squamous cell carcinomas (SCC). Treating clinical and preclinical lesions is mandatory in this group of patients due to the high changes of progression into SCC. On the other hand, prevention of AK should be considered because it plays a crucial role. Several studies have been published on immunocompetent patients, as well as on the management and prevention of AK, but not on immunosuppressed patients. This review aims to summarize the current knowledge on the management and prevention measures of AK in solid organ transplant recipients.

Secondary hypogammaglobulinemia in adults—A large retrospective cohort study / Hipogammaglobulinemia secundaria en adultos: estudio de cohorte retrospectiva

Background and objective: IgG replacement therapy (IgG-RT) has radically changed the clinical evolution of primary immunodeficiencies, yet the information regarding secondary hypogammaglobulinemia (SHG) is insufficient or conflicting. We aim to describe clinical features, evolution and treatment of SHG patients in our center. Methods: Dynamic retrospective cohort between January 2001 and July 2021 of adults with gamma globulin fraction <0.6g/dL in a serum protein electrophoresis and a coincident decrease of IgG levels – with a disease-related SHG or treatment that reduces serum immunoglobulins. Results: We included 1012 patients with SHG with a median follow-up of 5 years (IQR 2–8). Hematological diseases were identified in 95% of the patients and 61% received drugs related to SHG. Sixty five percent had more than one etiological factor associated with SHG. Infectious diseases were present in 69% of the patients, 48% had respiratory infections and 17% had severe infections. There was statistical association between respiratory and severe infections with multiple myeloma (MM), lymphoma and rituximab. MGUS had less infections and death compared with other etiologies. IgG-RT was indicated in 18.7% of the patients and 4.6% received it for more than 6 months with variable intervals. Among the latter group, there was a significant reduction of all-type infections and respiratory infections with IgG-RT (p<0.001), and it was consistent with similar findings in lymphoma, MM and all IgG levels subgroups. Conclusion: SHG was associated with more than one etiological factor and a high frequency of infections. IgG-RT indication was irregular yet still effective. It is relevant to consider IgG levels screening, monitoring and accurate indication of IgG-RT.(AU)

Antecedentes y objetivos: La IgG sustitutiva ha cambiado radicalmente la evolución de las inmunodeficiencias primarias, mientras que la información sobre hipogammaglobulinemia secundaria (HGS) es insuficiente y discordante. El objetivo del estudio es describir las características clínicas, evolución y tratamiento de pacientes con HGS. Métodos: Cohorte retrospectiva dinámica entre enero de 2001 y julio de 2021 de adultos con proteinograma y fracción de gammaglobulina <0,6g/dL y dosaje disminuido de IgG, con enfermedad o tratamiento que produzcan HGS. Resultados: Se incluyó a 1.012 pacientes con HGS con una mediana de seguimiento de 5 años (IIC 2-8). El 95% tenía enfermedad hematológica y el 61% recibió fármacos asociados a HGS. El 65% tenía más de un factor etiológico asociado con HGS. El 69% presentó infecciones de cualquier tipo, el 48% infecciones respiratorias y el 17%, infecciones graves. Hubo asociación significativa entre infecciones respiratorias y graves entre los subgrupos de mieloma múltiple, linfoma y rituximab. Los pacientes con MGUS tuvieron menor frecuencia de infecciones y muerte comparados con otros factores etiológicos. El 18,7% de los pacientes recibió IgG sustitutiva y el 4,6% de forma crónica, con intervalos variables. Los últimos tuvieron disminución significativa de infecciones de cualquier tipo e infecciones respiratorias con IgG sustitutiva (p<0,001), que se mantuvo en los subgrupos con mieloma múltiple, linfoma y todos los niveles de IgG. Conclusión: La HGS asoció más de un factor etiológico y alta frecuencia de infecciones. La indicación de IgG sustitutiva fue irregular, pero, aún así, efectiva. Se plantea considerar el dosaje de inmunoglobulinas, monitoreo y la adecuada indicación de IgG sustitutiva.(AU)

Incidence of herpes zoster in patients with inflammatory bowel disease. / Incidencia de herpes zóster en pacientes con enfermedad inflamatoria intestinal: estudio observacional y retrospectivo en dos hospitales españoles de tercer nivel.

BACKGROUND: Herpes zoster (HZ) is a prevalent disease caused by the reactivation of the varicella-zoster virus (VZV) and associated with chronic morbidity, particularly with post-herpetic neuralgia (PHN). Inflammatory bowel disease (IBD) has been associated with an increased risk of HZ, mainly when immunosuppressive treatment (IMT) is used. However, studies assessing the risk of HZ in IBD are scarce. AIMS: To evaluate the incidence rate and risk factors of HZ in IBD. METHODS: Retrospective study in IBD patients with a positive VVZ serology from two referral hospitals from the area of Barcelona. Diagnosis of HZ and its clinical features were recorded. RESULTS: A total of 398 IBD patients with a positive IgG-VVZ serology were identified. Fifty-eight percent of the patients received IMT (46.5% immunosuppressants monotherapy, 20.6% biologics monotherapy and, 32.7% combination therapy). After a median follow-up of 71 months (IQR 41.5-138.0), 17 (4.3%) patients developed HZ (cumulative incidence of 5.2 per 1000 person-year), 12 of them (70.6%) while receiving IMT. Median age at HZ episode was 38 years (IQR 27.5-52.5). Two (11%) developed PHN. Biological therapy was the only risk factor for developing HZ (OR 3.8 IC 95% 1.3-11.5; p=0.018). CONCLUSIONS: HZ is quite prevalent in IBD, occurring at early ages and particularly among patients using IMT. NPH appears to occur in a notable proportion of cases.

Secondary hypogammaglobulinemia in adults-A large retrospective cohort study.

BACKGROUND AND OBJECTIVE: IgG replacement therapy (IgG-RT) has radically changed the clinical evolution of primary immunodeficiencies, yet the information regarding secondary hypogammaglobulinemia (SHG) is insufficient or conflicting. We aim to describe clinical features, evolution and treatment of SHG patients in our center. METHODS: Dynamic retrospective cohort between January 2001 and July 2021 of adults with gamma globulin fraction <0.6g/dL in a serum protein electrophoresis and a coincident decrease of IgG levels - with a disease-related SHG or treatment that reduces serum immunoglobulins. RESULTS: We included 1012 patients with SHG with a median follow-up of 5 years (IQR 2-8). Hematological diseases were identified in 95% of the patients and 61% received drugs related to SHG. Sixty five percent had more than one etiological factor associated with SHG. Infectious diseases were present in 69% of the patients, 48% had respiratory infections and 17% had severe infections. There was statistical association between respiratory and severe infections with multiple myeloma (MM), lymphoma and rituximab. MGUS had less infections and death compared with other etiologies. IgG-RT was indicated in 18.7% of the patients and 4.6% received it for more than 6 months with variable intervals. Among the latter group, there was a significant reduction of all-type infections and respiratory infections with IgG-RT (p<0.001), and it was consistent with similar findings in lymphoma, MM and all IgG levels subgroups. CONCLUSION: SHG was associated with more than one etiological factor and a high frequency of infections. IgG-RT indication was irregular yet still effective. It is relevant to consider IgG levels screening, monitoring and accurate indication of IgG-RT.

mTOR inhibitors a potential predisposing factor for chronic hepatitis E: Results from the prospective collaborative CHES study (Chronic Hepatitis EScreening in patients with immune impairment and increased transaminases levels) / Los inhibidores de mTOR como potencial factor predisponente para la hepatitis crónica E: resultados del estudio prospectivo colaborativo CHES (Chronic Hepatitis E Screening in patients with immune impairment and increased transaminases levels)

Background: Chronic hepatitis E virus (HEV) in persons with immune impairment has a progressive course leading to a rapid progression to liver cirrhosis. However, prospective data on chronic HEV is scarce. The aim of this study was to determine the prevalence and risk factors for chronic HEV infection in subjects with immune dysfunction and elevated liver enzymes. Patients and methods: CHES is a multicenter prospective study that included adults with elevated transaminases values for at least 6 months and any of these conditions: transplant recipients, HIV infection, haemodialysis, liver cirrhosis, and immunosuppressant therapy. Anti-HEV IgG/IgM (Wantai ELISA) and HEV-RNA by an automated highly sensitive assay (Roche diagnostics) were performed in all subjects. In addition, all participants answered an epidemiological survey. Results: Three hundred and eighty-one patients were included: 131 transplant recipients, 115 cirrhosis, 51 HIV-infected subjects, 87 on immunosuppressants, 4 hemodialysis. Overall, 210 subjects were on immunosuppressants. Anti-HEV IgG was found in 94 (25.6%) subjects with similar rates regardless of the cause for immune impairment. HEV-RNA was positive in 6 (1.6%), all of them transplant recipients, yielding a rate of chronic HEV of 5.8% among solid-organ recipients. In the transplant population, only therapy with mTOR inhibitors was independently associated with risk of chronic HEV, whereas also ALT values impacted in the general model. Conclusions: Despite previous abnormal transaminases values, chronic HEV was only observed among solid-organ recipients. In this population, the rate of chronic HEV was 5.8% and only therapy with mTOR inhibitors was independently associated with chronic hepatitis E. (AU)

Introducción: La infección crónica por el virus de la hepatitis E (VHE) en personas con disfunción inmunitaria tiene un curso progresivo conllevando una rápida progresión a cirrosis hepática. Sin embargo, los datos prospectivos a este respecto son escasos. El objetivo de este estudio fue determinar la prevalencia y factores de riesgo para la infección crónica VHE en sujetos con disfunción inmunitaria y elevación de enzimas hepáticos. Pacientes y métodos: CHES es un estudio prospectivo multicéntrico que incluyó adultos con transaminasas elevadas durante al menos 6 meses y alguno de estos factores: receptores de trasplante, infección por VIH, hemodiálisis, cirrosis hepática o tratamiento inmunosupresor. En todos los sujetos se realizaron IgG/IgM anti-VHE (Wantai Elisa) y ARN-VHE por una técnica super sensible (Roche Diagnostics). Además, todos los participantes contestaron una encuesta epidemiológica. Resultados: 381 pacientes fueron incluidos: 131 trasplantados, 115 cirróticos, 51 infectados por VIH, 87 bajo inmunosupresores, 4 hemodiálisis. En total, 210 sujetos recibían inmunosupresores. La IgG anti-VHE fue positiva en 94 (25,6%) sujetos, con tasas similares en todas la causas de disfunción inmunitaria. El ARN-VHE fue positivo en 6 (1,6%) pacientes, todos ellos trasplantados, siendo la tasa de infección crónica VHE en receptores de órgano sólido del 5,8%. En la población de trasplantados, solo el tratamiento con inhibidores de mTOR se asoció de forma independiente a la hepatitis crónica VHE, mientras que los niveles de ALT impactaron en el modelo general. Conclusiones: A pesar de los niveles anormales de transaminasas, solo se objetivó hepatitis crónica VHE en trasplantados de órgano sólido. En esta población, la tasa de hepatitis crónica VHE fue del 5,8% y solo el tratamiento con inhibidores de mTOR se asoció de forma independiente a la hepatitis crónica E. (AU)

Absceso pulmonar en relación con un patógeno inusual / Lung abscess in relation with unusual pathogen

Un hombre de 57 años acudió a urgencias con astenia, mareo y tos con expectoración purulenta. Ingresó a cargo del Servicio de Neumología, y se objetivó en la imagen de tomografía axial computarizada un espacio aéreo grande en el lóbulo superior derecho. Esta lesión se atribuyó a un absceso pulmonar y se aisló Streptomyces albus en las muestras respiratorias. El género Streptomyces a menudo causa infecciones de la piel y tejidos blandos. Bacteriemia, neumonía y otros cuadros son raros. En nuestro caso, el paciente presentó un absceso pulmonar de gran tamaño, a pesar de los escasos síntomas descritos. La presentación del caso es atípica, dado que S. albus no suele causar abscesos pulmonares de manera aislada. (AU)

A 57-year-old man presented with asthenia, dizziness, and cough with purulent expectoration. He was admitted to the Pulmonology Unit, and a big air space in the right upper lobe was observed in computed tomography, which was characterized as a lung abscess, and Streptomyces albus was isolated. Streptomyces usually causes superficial skin and soft tissue infections. Bacteriemia, pneumonia, and other diseases are rarely seen. Our case is presented as a big lung abscess; nonetheless, our patient was paucisymptomatic. This case presentation describes the unusual phenomenon of a lung abscess caused by S. albus solely. (AU)

Enfermedad asociada a anticuerpos contra la glicoproteína de mielina de oligodendrocitos / Myelin oligodendrocyte glycoprotein antibody disease

Introducción: La enfermedad asociada a anticuerpos contra la glicoproteína de mielina del oligodendrocito (MOGAD, por sus siglas en inglés) es una entidad clínica recientemente identificada. La frecuencia de presentación del MOGAD es desconocida, pero se considera baja con respecto a otras enfermedades inflamatorias desmielinizantes. Materiales y métodos: Revisión narrativa de la literatura. Resultados: Las manifestaciones clínicas de esta condición son heterogéneas e incluyen neuritis óptica, mielitis, desmielinización multifocal del sistema nervioso central y encefalitis cortical. Se han descrito algunos hallazgos radiológicos que aumentan la sospecha diagnóstica, como el realce perineural del nervio óptico, el signo de la H en el cordón espinal y la resolución de lesiones T2 con el tiempo. El diagnóstico se basa en la detección de inmunoglobulinas G específicas contra MOG, en el contexto clínico adecuado. El tratamiento consiste en manejo de los ataques agudos con dosis altas de corticoides y en algunos casos se deberá considerar la inmunosupresión crónica, considerar la inmunosupresión crónica en pacientes con recurrencia o con discapacidad severa residual tras el primer evento. Conclusiones: En esta revisión narrativa se resumen los aspectos clave con respecto a la fisiopatología, las manifestaciones, el diagnóstico y el tratamiento de la MOGAD.

Introduction: The disease associated with antibodies against the myelin oligodendrocyte glycoprotein (MOGAD) is a recently identified clinical entity, with unknown frequency, but is considered low compared to other demyelinating inflammatory diseases. Materials And Methods: Narrative review. Results: The clinical manifestations are heterogeneous, ranging from optic neuritis or myelitis to multi-focal CNS demyelination or cortical encephalitis. There have been described characteristic MRI features that increase the diagnostic suspicion, such as perineural optic nerve enhancement, spinal cord H-sign or T2-lesion resolution over time. The diagnosis is based on the detection of specific G- immunoglobulins against MOG, in the suggestive clinical context. Acute treatment is based on high dose steroids and maintenance treatment is generally reserved for relapsing cases or patients with severe residual disability after the first attack. Conclusions: In this narrative review, fundamental aspects of pathophysiology, clinical and radiological manifestations, diagnosis and treatment of MOGAD are discussed.

Neumonía por Pneumocystis jirovecii asociada a hemorragia alveolar difusa en un paciente con trasplante renal

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.

Actinic Keratosis in Solid Organ Transplant Recipients: A Medical Literature Review. / Queratosis actínicas en pacientes trasplantados de órgano sólido: revisión de la literatura.

Pharmacological immunosuppression in solid organ transplant recipients is a significant risk factor in the occurrence of actinic keratosis (AK) and later progression into squamous cell carcinomas (SCC). Treating clinical and preclinical lesions is mandatory in this group of patients due to the high changes of progression into SCC. On the other hand, prevention of AK should be considered because it plays a crucial role. Several studies have been published on immunocompetent patients, as well as on the management and prevention of AK, but not on immunosuppressed patients. This review aims to summarize the current knowledge on the management and prevention measures of AK in solid organ transplant recipients.

Absceso subretiniano por Nocardia en paciente inmunodeprimido: a propósito de un caso / Subretinal abscess due to Nocardia in an immunosuppressed patient: A case report

La nocardiosis sistémica es una enfermedad poco frecuente. Su diseminación por vía hematógena al globo ocular lo es aún todavía más, con muy pocos casos documentados, por lo que su sospecha como posible diagnóstico en caso de absceso subretiniano no es la norma. Sin embargo, con unos antecedentes de inmunodepresión y enfermedad pulmonar, la imagen de fondo de ojo es enormemente indicativa. Presentamos el caso de un varón de 45 años inmunosuprimido, sin clínica pulmonar, que inició con una masa subretiniana que por su evolución es compatible con un absceso, diagnosticado etiológicamente en última instancia mediante vitrectomía como infección por Nocardia cyriacigeorgica, un patógeno emergente. Sumamos así nuestro caso, con sus peculiaridades, a otros para documentar una enfermedad que por su infrecuencia puede ser tardíamente diagnosticada (AU)

Systemic nocardiosis is a rarely occurring pathology, but its hematogenous spread across the eye is even less likely to occur, with only a few recorded cases. Therefore, it is not usually taken into account when a subretinal abscess is being considered for a diagnosis. However, when confronting a case with a history of immunosuppression and pulmonary disease, the examination of the ocular fondo may be a very successful approach. With such aim we introduce the case of a 45-year-old immunosuppressed male, without a history of pulmonary disease, whose subretinal mass evolution is accordant with an abscess. In the end, being etiologically diagnosed by means of a vitrectomy, it was concluded that the abscess was due to an infection of Nocardia cyriacigeorgica, an emergent pathogen. Thus the aforementioned case is to be considered in the present study, along others, in order to shed more light on a disease which may not be readily diagnosed on account of its infrequency (AU)

Impact of immunosuppression regimen on COVID-19 mortality in kidney transplant recipients: Analysis from a Colombian transplantation centers registry / Impacto de los esquemas de inmunosupresión en la mortalidad por COVID-19 en receptores de trasplante renal: análisis en centros de trasplante renal en Colombia

Backgroung The impact of immunosuppression in solid organ transplant recipients with SARS-CoV-2 infection is unknown. The knowledge about the behavior of different immunosuppression schemes in clinical outcomes is scarce. This study aimed to determine the risk of death in kidney transplant recipients with COVID-19 under two different schemes of immunosuppression. Methods We describe our experience in kidney transplant recipients with SARS-CoV-2 infection in seven transplant centers during the first year of the pandemic before starting the vaccination programs in the city of Bogotá. Demographic characteristics, clinical presentation, immunosuppression schemes at presentation, and global treatment strategies were compared between recovered and dead patients; survival analysis was carried out between calcineurin inhibitors based regimen and free calcineurin inhibitors regimen. Results Among 165 confirmed cases, 28 died (17%); the risk factors for mortality identified in univariate analysis were age older than 60 years (p=.003) diabetes (p=.001), immunosuppression based on calcineurin inhibitors (CNI) (p=.025) and patients receiving steroids (p=.041). In multivariable analysis, hypoxemia (p=.000) and calcineurin inhibitors regimen (p=.002) were predictors of death. Survival analysis showed increased mortality risk in patients receiving CNI based immunosuppression regimen vs. CNI free regimens mortality rates were, respectively, 21.7% and 8.5% (p=.036). Conclusions Our results suggest that the calcineurin inhibitors probably do not provide greater protection compared to calcineurin inhibitor free schemes being necessary to carry out analyzes that allow us to evaluate the outcomes with different immunosuppression schemes in solid organ transplant recipients with SARS-CoV-2 infection (AU)

Introducción El impacto de los diferentes esquemas de inmunosupresión en receptores de trasplante de órganos sólidos es desconocido. El conocimiento del comportamiento de la enfermedad bajo diferentes esquemas de inmunosupresión es escaso. Nuestra experiencia intenta determinar el riesgo de muerte en receptores de trasplante renal con COVID-19 bajo dos esquemas diferentes de inmunosupresión. Métodos Describimos la experiencia en receptores de trasplante renal con infección por SARS-CoV-2 en siete centros de trasplante renal en la ciudad de Bogotá, durante el primer año de pandemia y previo al inicio de los programas de vacunación. Las características demográficas, la presentación clínica, los esquemas de inmunosupresión y las estrategias de tratamiento fueron comparadas entre pacientes recuperados y fallecidos, un análisis de sobrevida fue llevado a cabo entre esquemas basados en inhibidores de calcineurina y esquemas libres de inhibidores de calcineurina. Resultados Entre los 165 casos confirmados, 28 murieron (17%), los factores de riesgo identificados para mortalidad en el análisis univariado fueron: edad mayor de 60 años, diabetes, un esquema de inmunosupresión basado en inhibidores de calcineurina y pacientes recibiendo esteroides en el momento del diagnóstico. En el análisis multivariado, la presencia de hipoxemia en el momento del diagnóstico (p = 0,000) y un esquema de inmunosupresión basado en inhibidores de calcineurina (p = 0,002) fueron predictores independientes de mortalidad. El análisis de sobrevida encontró un riesgo mayor de mortalidad en pacientes bajo esquemas de inmunosupresión con inhibidores de calcineurina vs. aquellos libres de inhibidores de calcineurina, con tasas de mortalidad respectivas en 21,7 y 8,5% (p = 0,036). Conclusiones Nuestros resultados sugieren que los inhibidores de calcineurina no aportan mayor protección en pacientes con trasplante renal y COVID-19 en comparación con esquemas libres de inhibidores de calcineurina (AU)

Management of immunosuppressive therapy in kidney transplant recipients with COVID-19. A multicentre national study derived from the Spanish Society of Nephrology COVID registry.

INTRODUCTION: SARS CoV2 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-CoV2 infection, as well as renal function and anti-HLA antibodies in kidney transplant patients 6 months after COVID19 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. RESULTS: renal transplant recipients with COVID19 were included (62.6% male), with a mean age of 57.5 years. The predominant immunosuppressive treatment prior to COVID19 was triple therapy with prednisone, tacrolimus and mycophenolic acid (54.6%) followed by m-TOR inhibitor regimens (18.6%). After diagnosis of infection, mycophenolic acid was discontinued in 73.8% of patients, m-TOR inhibitor in 41.4%, tacrolimus in 10.5% and cyclosporin A in 10%. In turn, 26.9% received dexamethasone and 50.9% were started on or had their baseline prednisone dose increased. Mean creatinine before diagnosis of COVID19, at diagnosis and at 6 months was: 1.7 ±â€¯0.8, 2.1 ±â€¯1.2 and 1.8 ±â€¯1 mg/dl respectively (p < 0.001). 56.9% of the patients (N = 350) were monitored for anti-HLA antibodies. 94% (N = 329) had no anti-HLA changes, while 6% (N = 21) had positive anti-HLA antibodies. Among the patients with donor-specific antibodies post-COVID19 (N = 9), 7 patients (3.1%) had one immunosuppressant discontinued (5 patients had mycophenolic acid and 2 had tacrolimus), 1 patient had both immunosuppressants discontinued (3.4%) and 1 patient had no change in immunosuppression (1.1%), these differences were not significant. CONCLUSIONS: The management of immunosuppressive therapy after diagnosis of COVID19 was primarily based on discontinuation of mycophenolic acid with very discrete reductions or discontinuations of calcineurin inhibitors. This immunosuppression management did not influence renal function or changes in anti-HLA antibodies 6 months after diagnosis.

Mycobacterial infection after COVID-19 pneumonia / Infección por micobacterias tras neumonía por COVID-19

A 69-year-old man with a history of hypertrophic cardiomyopathy and major depressive disorder was admitted to the Emergency Department with fever, weakness, and shortness of breath. He was diagnosed with acute respiratory distress syndrome due to COVID-19 and received oxygen and steroids during a one-month hospital stay. After discharge, he continued steroids and home oxygen therapy for nearly two years. CT scans revealed bronchiectasis and ground glass opacities related to COVID-19. He developed pulmonary nodules and M. intracellulare infection, which were treated with rifampicin, ethambutol, and azithromycin. After six months of treatment, the patient showed clinical and radiological improvement (AU)

Un hombre de 69 años con antecedentes de miocardiopatía hipertrófica y trastorno depresivo mayor acudió a urgencias por fiebre, debilidad y dificultad respiratoria. Se le diagnosticó síndrome de distrés respiratorio agudo debido a COVID-19 y fue ingresado en planta de neumología, donde recibió oxígeno y esteroides durante 1 mes. Después del alta continuó con esteroides y oxigenoterapia domiciliaria durante casi 2 años. Las tomografías objetivaron bronquiectasias y opacidades en vidrio deslustrado relacionadas con la COVID-19. Desarrolló nódulos pulmonares e infección por Mycobacterium intracellulare, siendo tratado con rifampicina, etambutol y azitromicina. Después de 6 meses de tratamiento, el paciente mostró mejoría clínica y radiológica (AU)

Subretinal abscess due to nocardia in an immunosuppressed patient: a case report.

Systemic nocardiosis is a rarely occurring pathology, but its hematogenous spread across the eye is even less likely to occur, with only a few recorded cases. Therefore, it is not usually taken into account when a subretinal abscess is being considered for a diagnosis. However, when confronting a case with a history of immunosupression and pulmonary disease, the examination of the ocular fundus may be a very successful approach. With such aim we introduce the case of a 45-year-old immunosupressed male, without a history of pulmonary disease, whose subretinal mass evolution is accordant with an abscess. In the end, being etiologically diagnosed by means of a vitrectomy, it was concluded that the abscess was due to an infection of nocardia cyriacigeorgica, an emergent pathogen. Thus the aforementioned case is to be considered in the present study, along others, in order to shed more light on a disease which may not be readily diagnosed on account of its infrequency.

Reduction in the risk of progression of solid organ transplant recipients infected by SARS-CoV-2 treated with monoclonal antibodies / Reducción del riesgo de progresión en receptores de trasplantes infectados por SARS-CoV-2 tratados con anticuerpos monoclonales

Recipients of solid organ transplants (SOT) are at higher risk of infection by SARS-CoV-2 virus especially due to chronic immunosuppression therapy and frequent multiple comorbid conditions. COVID-19 is a potentially life-threatening disease in SOT recipients, with an increased likelihood of progressing to severe disease, with the need of hospitalization, admission to the intensive care unit (ICU) and mechanical ventilatory support. This article presents an updated review of different aspects related to the outcome of COVID-19 in SOT recipients. In nvaccinated SOT recipients, COVID-19 is associated with a high mortality rate, in-patient care and ICU admission, and impaired graft function or rejection in severe disease. In vaccinated SOT recipients even after full vaccination, there is a reduction of the risk of mortality, but the course of COVID-19 may continue to be severe, influenced by the time from transplant, the net state of immunosuppression and having suffered graft rejection or dysfunction. SOT recipients develop lower immunity from mRNA vaccines with suboptimal response. Treatment with mAbs provides favorable outcomes in non-hospitalized SOT recipients at high risk for severe disease, with lower rates of hospitalization, emergency department visits, ICU care, progression to severe disease, and death. However, broad vaccination and therapeutic options are required, particularly in light of the tendency of the SARS-CoV-2 virus to adapt and evade both natural

Los receptores de trasplantes de órganos sólidos (TOS) presentan un alto riesgo de infección por el virus SARS-CoV-2 debido al tratamiento inmunosupresor y múltiples comorbilidades. La COVID-19 puede ser potencialmente mortal en receptores de TOS, con un aumento de la probabilidad de progresión a enfermedad grave. Este trabajo presenta una revisión actualizada del impacto de la COVID-19 en receptores de TOS. En los receptores de TOS no vacunados, la COVID-19 se asocia con una alta tasa de mortalidad, hospitalización, ingreso en la UCI y deterioro del injerto o rechazo. En los pacientes vacunados, incluso con pauta de vacunación completa, se reduce el riesgo de mortalidad, pero el curso de la COVID-19 puede continuar siendo grave en función del tiempo desde el trasplante, el estado neto de inmunosupresión y haber sufrido rechazo o disfunción del injerto. Los receptores de TOS presentan una baja inmunogenicidad a las vacunas de ARNm y respuesta subóptima. El tratamiento con anticuerpos monoclonales (AMC) en receptores de TOS no hospitalizados con alto riesgo de enfermedad grave, se asocia con menores tasas de hospitalización, visitas a urgencias, ingreso en UCI, progresión a enfermedad grave y muerte. Sin embargo, se requieren nuevas vacunas y opciones terapéuticas, teniendo en cuenta la tendencia del virus SARS-CoV-2 a adaptarse y a evadir tanto la inmunidad natural como la inducida por la vacuna (Au)and vaccine-induced immunity (AU)

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)