Asociación de trasplante de progenitores hematopoyéticos y síndrome de Parsonage-Turner: ¿coincidencia o relación causa-efecto? / Association between hematopoietic stem cell transplantation and Parsonage Turner syndrome: coincidence or cause-effect relationship?

El síndrome de Parsonage-Turner o plexopatía braquial idiopática es una inflamación total o parcial del plexo braquial cuya presentación típica es una omalgia intensa y súbita, seguida de debilidad braquial y amiotrofia precoz. La etiología es desconocida, aunque se propone un mecanismo inmunomediado.El trasplante de progenitores hematopoyéticos es un tratamiento bien establecido de las neoplasias hematológicas y tiene un papel creciente en el tratamiento de enfermedades autoinmunes. Los efectos adversos neurológicos son probablemente infradiagnosticados.La asociación del síndrome de Parsonage-Turner y el trasplante de progenitores hematopoyéticos es muy poco conocida. Describimos dos casos clínicos de plexopatía braquial idiopática tras trasplante de células stem (progenitores) hematopoyéticas (TPH).La reconstitución del sistema inmune tras un trasplante de progenitores hematopoyéticos puede ser un desencadenante de plexopatía braquial, aunque se necesitan más estudios para entender la fisiopatología de esta entidad y establecer su relación causal con el trasplante. (AU)

Parsonage-Turner syndrome or idiopathic brachial neuritis is a total or partial inflammation of the brachial plexus, with a typical presentation as a sudden and very intense pain in the shoulder, followed by weakness and early amyotrophy. The etiology is still unknown, although an immune mediated mechanism is thought to be involved.Hematopoietic stem cell transplantation is a well-established treatment for hematological malignancies, but with a growing implication in the treatment of autoimmune diseases. The neurological side effects are probably underdiagnosed.The association of the Parsonage-Turner syndrome and the hematopoietic stem cell transplantation is scarce. We describe two clinical cases of idiopathic brachial plexopathy after hematopoietic stem cell transplantation.The reconstruction of the immune system after a transplant may be the trigger of a brachial plexopathy, but more studies are necessary for the etiology of this disease to be understood and to establish a cause-effect relation with the transplant. (AU)

Why your doctor is not an algorithm: exploring logical principles of different clinical inference methods using liver transplantation as a model. / Por qué mi médico no es un algoritmo? Fundamentos lógicos de los diferentes métodos de inferencia clínica a través del ejemplo del trasplante hepático.

The development of machine learning (ML) tools in many different medical settings is largely increasing. However, the use of the resulting algorithms in daily medical practice is still an unsolved challenge. We propose an epistemological approach (i.e., based on logical principles) to the application of computational tools in clinical practice. We rely on the classification of scientific inference into deductive, inductive, and abductive comparing the characteristics of ML tools with those derived from evidence-based medicine [EBM] and experience-based medicine, as paradigms of well-known methods for generation of knowledge. While we illustrate our arguments using liver transplantation as an example, this approach can be applied to other aspects of the specialty. Regarding EBM, it generates general knowledge that clinicians apply deductively, but the certainty of its conclusions is not guaranteed. In contrast, automatic algorithms primarily rely on inductive reasoning. Their design enables the integration of vast datasets and mitigates the emotional biases inherent in human induction. However, its poor capacity for abductive inference (a logical mechanism inherent to human clinical experience) constrains its performance in clinical settings characterized by uncertainty, where data are heterogeneous, results are highly influenced by context, or where prognostic factors can change rapidly.

Blastic plasmacytoid dendritic cell neoplasm: a single-center experience. Clinical characterization, mutational landscape, and clinical outcome of patients undergoing hematopoietic stem cell transplantation intensive therapy.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematodermic neoplasm usually involving the skin. In this retrospective case series, 10 cases of BPDCN were identified, 90% of which had skin involvement and exhibited predominantly violaceous nodules and/or bruise-like plaques. Skin lesions showed diffuse or nodular dermal-based infiltrates of intermediate sized blasts with a grenz zone. Tumor immunophenotyping was CD4(+), CD56(+), CD123(+) and CD303(+). The most frequently mutated genes according to targeted next-generation sequencing were TET2 (3/7) and NRAS (2/7). Multiagent chemotherapy (CT) was administered as first-line therapy, and a total of 5 patients underwent allogenic hematopoietic stem cell transplantation (allo-HSCT). Better outcomes were observed in younger patients and those treated with acute lymphoblastic leukemia (ALL)-like CT followed by allo-HSCT. This study shows the clinical range of cutaneous lesions of BPDCN. Despite the absence of a gold standard therapy, patients treated with myeloablative intensive regimens and allo-HSCT seem to have a more favorable prognosis.

[Relationship between frailty and functional status in lung transplant candidates]. / Relación entre la fragilidad y la capacidad funcional en los pacientes candidatos a trasplante de pulmón.

INTRODUCTION: Lung transplant (LT) is one of the therapeutic options for patients with terminal respiratory diseases. It is highly important to incorporate the functional status and frailty assessment into the selection process of candidates for LT. OBJECTIVES: Identify the prevalence of frailty in the LT waiting list. Study the relationship between frailty, functional status, Lung Allocation Score (LAS) and muscular dysfunction. METHODOLOGY: Descriptive transversal study of patients on the waiting list for LT. POPULATION: 74 patients with chronic respiratory diseases assessed by the lung transplant committee and accepted to be transplanted in a university hospital in Barcelona. The outcome variables were frailty status was evaluate for SPPB test, functional capacity was evaluate for the six-minute walking test (6MWT) and muscular dysfunction. The results were analyzed with the statistical package STATA 12. RESULTS: Sample of 48 men and 26 women, with a median age of 56.55 years (SD 10.87. The prevalence of frailty assessed with the SPPB was 33.8% (8.1% are in frailty and 25.7% are in a state of pre-frailty). There is a relationship between the SPPB, 6MWT and maximal inspiratory pressure, but not with others force values. There is a relationship between the risk of frailty (scores below 9 in SPPB) and the meters walked in 6 but not with the LAS. CONCLUSIONS: The risk of frailty in patients with terminal chronic respiratory diseases is high. Frailty is related with functional capacity, but not with LAS.

Survival analysis of the surgical treatment of hepatocellular carcinoma at a tertiary care center.

INTRODUCTION AND AIMS: Hepatocellular carcinoma (HCC) is a primary malignant tumor of liver epithelial cells and is the most frequent primary liver cancer. The broadening of transplantation and resectability criteria has made therapeutic decisions more complex. Our aim was to describe the clinical and survival characteristics of patients with HCC treated through resection or liver transplantation at our hospital and identify the presence of factors that enable outcome prediction and facilitate therapeutic decision-making. MATERIALS AND METHODS: Patients with HCC that underwent surgery with curative intent at the Hospital Universitario Marqués de Valdecilla, within the time frame of 2007 and 2017, were retrospectively identified. Survival, mortality, disease-free interval, and different outcome-related variables were analyzed. RESULTS: Ninety-six patients with a mean follow-up after surgery of 44 months were included. Overall mortality and recurrence were higher in the resection group. Mean survival was 51.4 months in the liver transplantation group and 37.5 months in the resection group, and the disease-free interval was 49.4 ±â€¯37.2 and 27.4 ±â€¯28.7 months, respectively (p = 0.002). The tumor burden score was statistically significant regarding risk for recurrence and specific mortality. CONCLUSIONS: There appears to be no patient subgroup in whom the results of surgical resection were superior or comparable to those of transplantation. Tumor burden determination could be a useful tool for patient subclassification and help guide therapeutic decision-making.

Critical pathway for deceased donors: An analysis in three regions of Colombia / Ruta crítica de donantes fallecidos: un análisis de tres regiones en Colombia

Introduction. The critical pathway for deceased donation offers a methodical framework for guiding the donation process. It not only serves to assess performance but also to identify areas of potential improvement. Therefore, the identification and selection of potential organ donors (POD) is a key process. This study aims to describe the critical pathway for deceased donation in a cohort of POD in three regions (CRT1, CRT2, and CRT5) of Colombia. Methods. We retrospectively reviewed data of POD assessed from January 2022 to December 2022. General characteristics of POD, diagnosis, contraindication causes, and organ procurement were described. Analysis was conducted using the Chi-squared test for categorical variables and the Mann-Whitney test for quantitative variables. Results. Within the cohort of 1451 assessed POD, 441 (30.3%) were diagnosed with brain death. Among potential donors after brain death, 198 (44.9%) were eligible donors (medically suitable). Of these, 157 donors (79.3%) became actual donors (undergoing operative incision for organ recovery), with 147 (93,6 %) having at least one organ recovered (actual donors with organ recovery). Ultimately, 411 utilized organs were utilized. Additionally, there were observed differences in the characteristics of donors from different regions. Conclusion. This study reports the critical pathway for deceased donation in a cohort of POD in three regions of Colombia. This provides useful information and helps to gain insight and understanding into the process of organ donation and organ procurement in order to take actions that could improve the donation rates.

Introducción. La ruta crítica de donantes fallecidos permite un enfoque sistemático para la donación de riñón, y, proporciona una herramienta para evaluar el rendimiento de áreas de mejora potencial. La selección de posibles donantes de órganos (PDO) es un proceso clave. El objetivo de este estudio fue describir la ruta crítica para la donación de fallecidos en una cohorte de PDO en tres regiones de Colombia. Métodos. Estudio retrospectivo de PDO evaluados durante 2022. Se describieron las características generales de los PDO, el diagnóstico y las causas de contraindicación. El análisis se llevó a cabo utilizando la prueba de Chi-cuadrado para las variables categóricas y la prueba de Mann-Whitney para las variables cuantitativas. Resultados. Entre los 1451 POD evaluados, 441 (30,3 %) fueron diagnosticados con muerte cerebral. De los posibles donantes después de la muerte cerebral, 198 (44,9 %) fueron donantes elegibles (adecuados desde el punto de vista médico). Entre ellos, 157 donantes (79,3 %) fueron donantes reales (en quienes se realizó una incisión operatoria con la intención de recuperar órganos) y 147 (93,6 %) tuvieron al menos un órgano recuperado (donantes reales con recuperación de órganos). Finalmente, se identificaron 411 órganos utilizados. Conclusión. Este estudio reporta la ruta crítica para la donación de fallecidos en una cohorte de POD en tres regiones de Colombia. Esto proporciona información útil, ayuda a obtener conocimientos y comprender el proceso de donación y obtención de órganos, para tomar medidas que puedan mejorar las tasas de donación.

Recomendaciones sobre el manejo clínico de la alopecia androgénica: un documento de consenso del Grupo Español de Tricología de la Academia Española de Dermatología y Venereología / Recommendations on the Clinical Management of Androgenetic Alopecia: A Consensus Statement From the Spanish Trichology Group of the Spanish Academy of Dermatology and Venererology (AEDV)

El tratamiento de la alopecia androgénica (AGA) puede ser complejo para el clínico debido a la amplia gama de terapias disponibles, en muchos casos con escasos ensayos clínicos disponibles, y con muchas de las opciones de tratamiento sin aprobación de uso en la AGA según su ficha técnica. Este documento de consenso sobre el manejo de la AGA se ha elaborado siguiendo un método Delphi, en el que han participado 34 dermatólogos miembros del Grupo Español de Tricología de la Academia Española de Dermatología y Venereología. Tras 2 rondas de votaciones, se consensuaron 138 de los 160 ítems propuestos (86%), estructurados en 4 bloques de recomendaciones: generalidades, tratamiento farmacológico, procedimientos y trasplante capilar, y casos especiales. Este documento de consenso se apoya en la evidencia científica disponible y en la opinión de expertos para ayudar a los profesionales en el manejo de la AGA en la práctica clínica diaria.(AU)

Androgenetic alopecia can be challenging to treat due to the wide range of available treatments, most of which are not based on evidence from clinical trials. In addition many of the options do not include androgenetic alopecia among the approved indications according to their summaries of product characteristics. A panel of 34 dermatologists from the Spanish Trichology Society of the Spanish Academy of Dermatology and Venereology (AEDV) used the Delphi method to develop a consensus statement on the management of androgenetic alopecia. Over a 2-round process the experts agreed on 138 (86%) of the 160 proposed items, which were structured into 4 blocks of recommendations: general considerations, pharmacologic treatment, procedures and hair transplant, and special cases. The resulting consensus statement based on expert opinion of the scientific evidence can guide professionals in the routine management of androgenetic alopecia.(AU)

[Translated article] Recommendations on the Clinical Management of Androgenetic Alopecia: A Consensus Statement From the Spanish Hair Disorders Group of the Spanish Academy of Dermatology and Venererology (AEDV) / Recomendaciones sobre el manejo clínico de la alopecia androgénica: un documento de consenso del Grupo Español de Tricología de la Academia Española de Dermatología y Venereología

El tratamiento de la alopecia androgénica (AGA) puede ser complejo para el clínico debido a la amplia gama de terapias disponibles, en muchos casos con escasos ensayos clínicos disponibles, y con muchas de las opciones de tratamiento sin aprobación de uso en la AGA según su ficha técnica. Este documento de consenso sobre el manejo de la AGA se ha elaborado siguiendo un método Delphi, en el que han participado 34 dermatólogos miembros del Grupo Español de Tricología de la Academia Española de Dermatología y Venereología. Tras 2 rondas de votaciones, se consensuaron 138 de los 160 ítems propuestos (86%), estructurados en 4 bloques de recomendaciones: generalidades, tratamiento farmacológico, procedimientos y trasplante capilar, y casos especiales. Este documento de consenso se apoya en la evidencia científica disponible y en la opinión de expertos para ayudar a los profesionales en el manejo de la AGA en la práctica clínica diaria.(AU)

Androgenetic alopecia can be challenging to treat due to the wide range of available treatments, most of which are not based on evidence from clinical trials. In addition many of the options do not include androgenetic alopecia among the approved indications according to their summaries of product characteristics. A panel of 34 dermatologists from the Spanish Trichology Society of the Spanish Academy of Dermatology and Venereology (AEDV) used the Delphi method to develop a consensus statement on the management of androgenetic alopecia. Over a 2-round process the experts agreed on 138 (86%) of the 160 proposed items, which were structured into 4 blocks of recommendations: general considerations, pharmacologic treatment, procedures and hair transplant, and special cases. The resulting consensus statement based on expert opinion of the scientific evidence can guide professionals in the routine management of androgenetic alopecia.(AU)

Efficacy and safety of mRNA1273 SARS-CoV-2 vaccination in hematopoietic stem cell transplant recipients: Single center experience

Background: COVID-19 represents a worldwide pandemic and vaccination remains the most effective preventive strategy. Among hematological patients, COVID-19 has been associated with a high mortality rate. Vaccination against SARS-CoV-2 has shown high efficacy in reducing community transmission, hospitalization and deaths related to severe COVID-19 disease. However, patients with impaired immunity may have lower sero-responsiveness to vaccination.MethodsThis study focuses on hematopoietic stem cell transplantation (HSCT) recipients. We performed a unicenter, prospective, observational study of a cohort of 31 allogeneic and 56 autologous-HSCT recipients monitored between March 2021 and May 2021 for serological response after COVID-19 vaccination with two doses of mRNA1273 vaccine (Moderna). In order to determine seroconversion, serological status before vaccination was studied.ResultsAt a median range of 75 days after the second vaccine dose, seroconversion rates were 84% and 85% for the autologous and allogeneic-HSCT groups, respectively. We confirmed some potential risk factors for a negative serological response, such as receiving anti-CD20 therapy in the previous year before vaccination, a low B-lymphocyte count and hypogammaglobulinemia. Neutralizing antibodies were quantified in 44 patients, with a good correlation with serological tests. Adverse events were minimal.ConclusionmRNA1273 vaccination is safe and effective in HSCT recipients, especially in those presenting recovered immunity. (AU)

Introducción: Entre los pacientes hematológicos, la COVID-19 se ha asociado a una mayor mortalidad. La vacunación frente a SARS-CoV-2 es la principal estrategia de prevención y ha demostrado eficacia en la reducción de la transmisión, de la hospitalización y de la tasa de mortalidad. Aun así, los pacientes oncohematológicos con un sistema inmunológico disfuncional podrían presentar una respuesta menor a la vacunación.MétodosEstudio unicéntrico, prospectivo y observacional, con una cohorte de 31 receptores de un trasplante alogénico de progenitores hematopoyéticos y de 56 receptores de un trasplante autólogo que recibieron la vacunación frente a SARS-CoV-2 entre marzo de 2021 y mayo de 2021, con 2 dosis de la vacuna mRNA1273 (Moderna). Para poder determinar la tasa de seroconversión, se determinó el estado serológico previamente a la vacunación y posteriormente se monitorizó la respuesta serológica.ResultadosCon un tiempo medio de seguimiento de 75 días después de la segunda vacuna, la tasa de seroconversión fue del 84%, y del 85% en el grupo receptor de trasplante autólogo y alogénico, respectivamente. Se confirmaron algunos potenciales factores de riesgo para la ausencia de respuesta serológica, como haber recibido terapias anti-CD20, un recuento bajo de linfocitos B y la hipogammaglobulinemia. En 44 pacientes se cuantificaron títulos de anticuerpos neutralizantes, con buena correlación con los test serológicos. Los efectos adversos de la vacuna fueron mínimos.ConclusiónLa vacunación con mRNA1273 es segura y efectiva en los pacientes receptores de un trasplante de progenitores hematopoyéticos, especialmente en los que presentan reconstitución inmune previa. (AU)

El paradigma de la irradiación corporal total en la leucemia linfoblástica aguda: efectividad terapéutica frente a los desafíos de toxicidad / The paradigm of total body irradiation in acute lymphoblastic leukemia: Therapeutic effectiveness against the challenges of toxicity

Introducción: La irradiación corporal total (ICT) forma parte del acondicionamiento mieloablativo del trasplante de progenitores hematopoyéticos (TPH) en hemopatías malignas. Esta terapia ha demostrado recientemente mayor supervivencia en leucemia linfoblástica aguda (LLA) frente a regímenes basados en quimioterapia. Sin embargo, los efectos secundarios son una limitación importante, especialmente en la población pediátrica.Pacientes y métodosAnalizamos retrospectivamente la supervivencia de pacientes con LLA que recibieron un TPH en un hospital terciario entre los años 1996 a 2009 (N=69 TPH en 57 pacientes). Diferenciamos una cohorte que había recibido ICT (N=44) y otra que no (N=25). Posteriormente entrevistamos a los supervivientes del grupo ICT con un mínimo de 10 años de seguimiento (N=18), preguntando acerca de la presencia de efectos secundarios.ResultadosLa supervivencia global (SG) a los 2 y 5 años fue del 79,1 y 65,2%, respectivamente para el grupo ICT y del 66,2 y 55,8% para el grupo no ICT, aunque esta diferencia no fue significativa (p=0,31). La supervivencia libre de evento (SLE) a los 2 y 5 años fue del 77,3 y 63,6%, respectivamente para el grupo ICT y del 56 y 32% para el grupo no ICT (p=0,02). La probabilidad de recidiva (PR) a los 2 años habiendo recibido ICT fue del 10% y sin haber recibido ICT del 28,6% (p=0,005). Los supervivientes que recibieron ICT desarrollaron neoplasias secundarias (39%), dislipemia (67%), alteraciones cognitivas (44%), infecciones respiratorias de repetición (39%), alteraciones tiroideas (45%), insuficiencia ovárica precoz (89%), cataratas (22%) y problemas psicológicos (44%), aunque la calidad de vida, valorada por ellos mismos, fue considerada como buena para el 83% de los encuestados.ConclusionesLos pacientes que recibieron ICT tuvieron significativamente mayor SLE y menor PR. Sin embargo, los efectos adversos son frecuentes e importantes, aunque no afectan subjetivamente a la calidad de vida. (AU)

Introduction: Total body irradiation (TBI) is part of the myeloablative conditioning for hematopoietic stem cell transplantation (HSCT) in malignant hematologic disorders. This therapy has recently shown improved survival in acute lymphoblastic leukemia (ALL) compared to chemotherapy-based regimens. However, side effects are a significant limitation, especially in the pediatric population.Patients and methodsWe retrospectively analyzed the survival of patients with ALL who underwent an HSCT at a tertiary hospital between 1996 and 2009 (N=69 HSCT in 57 patients). We differentiated a cohort that received TBI (N=44) from another that did not (N=25). Subsequently, we interviewed the survivors from the TBI group with a minimum of 10 years of follow-up (N=18), asking about the presence of side effects.ResultsThe overall survival (OS) at 2 and 5 years was 79.1% and 65.2% respectively for the TBI group and 66.2% and 55.8% for the non-TBI group, although this difference was not significant (P=.31). The event-free survival (EFS) at 2 and 5 years was 77.3% and 63.6% respectively for the TBI group and 56% and 32% for the non-TBI group (P=.02). The probability of relapse (PR) at 2 years for those who received TBI was 10% compared to 28.6% for those who did not receive TBI (P=.005). Survivors who received TBI developed secondary neoplasms (39%), dyslipidemia (67%), cognitive impairments affecting memory (44%), recurrent respiratory infections (39%), thyroid abnormalities (45%), premature ovarian failure (89%), cataracts (22%), and psychological problems (44%). However, the quality of life, as self-assessed by the patients, was considered good for 83% of the participants.ConclusionsPatients who received TBI had significantly higher EFS and lower PR. However, adverse effects are frequent and significant, although they do not subjectively affect quality of life. (AU)

Re-Descemet Membrane Endothelial Keratoplasty (DMEK) con preservación del injerto original tras free roll en cámara anterior: a propósito de un caso / Re-descemet membrane endothelial keratoplasty (DMEK) with preservation of the original graft after free-roll in the anterior chamber: a case report

Introducción: Las queratoplastias lamelares han supuesto un gran impacto en el manejo del edema corneal por disfunción endotelial. Las técnicas de trasplante mínimamente invasivo como la Descemet Membrane Endothelial Keratoplasty (DMEK) han permitido reducir la morbilidad que suponía la realización de una queratoplastia penetrante en este tipo de pacientes. Aun así, se trata de técnicas complejas que no están exentas de complicaciones, y que requieren una larga línea de aprendizaje quirúrgico y una aún más exigente experiencia en el manejo postoperatorio.Caso clínicoUna mujer de 89 años afecta de distrofia endotelial de Fuchs e intervenida de cirugía combinada de catarata y DMEK, presentó a las 24h de la intervención un edema estromal de predominio inferior y un despegamiento sectorial del injerto. Tras un re-bubbling en consultas y 4 días más tarde, se observó el injerto enrollado y libre en cámara anterior.Se intervino de re-DMEK con preservación del injerto original tras 24h, con desepitelización para optimizar la visualización. Se tiñó el injerto con azul tripán y se protegió el estroma posterior con aire. Se reimplantó el injerto bajo maniobras intraoculares y con burbuja de aire.A las 24h de la cirugía se observó el injerto adherido, con una gran disminución del edema estromal. Un mes después, la paciente presentaba una córnea transparente, una persistente adhesión completa del injerto y una agudeza visual de 0,9.ConclusiónEl hallazgo del free roll en cámara anterior tras cirugía de DMEK constituye la forma más compleja de despegamiento del injerto. El edema corneal, así como la disposición de las diferentes estructuras intraoculares son condicionantes a tener en cuenta para la resolución quirúrgica de esta complicación. En muchos casos el reposicionamiento quirúrgico del injerto es factible, hecho que implica ahorrar costes sin necesidad de utilizar nuevos tejidos corneales donantes. (AU)

Introduction: Lamellar keratoplasties have had a great impact in the management of corneal edema due to endothelial dysfunction. Minimally invasive transplant techniques such as descemet membrane endothelial keratoplasty (DMEK) have helped to reduce the morbidity involved in performing penetrating keratoplasty in this type of patient. Even so, these are complex techniques that are not free of complications and require a long line of surgical learning and an even more demanding experience in postoperative management.Clinical caseAn 89-year-old woman suffering from Fuchs endothelial dystrophy and undergoing combined cataract and DMEK surgery presented stromal edema predominantly inferior and sectoral detachment of the graft 24h after the intervention. After re-bubbling in consultations and 4 days later, the graft was observed rolled and free in the anterior chamber.She underwent re-DMEK with preservation of the original graft after 24h, with de-epithelialization to optimize visualization. The graft was stained with trypan blue and the posterior stroma was protected with air. The graft was reimplanted under intraocular maneuvers and with an air bubble.Twenty four hours after surgery, the adhered graft was observed, with a great decrease in stromal edema. One month later, the patient had a clear cornea, persistent complete graft adhesion, and visual acuity of 0.9.ConclusionThe discovery of free roll in the anterior chamber after DMEK surgery constitutes the most complex form of graft detachment. Corneal edema as well as the arrangement of the different intraocular structures are conditions to be considered for the surgical resolution of this complication. In many cases, surgical repositioning of the graft is feasible, which means saving costs without the need to use new donor corneal tissues. (AU)

Levosimendán ambulatorio repetitivo como puente al trasplante cardiaco / Repetitive ambulatory levosimendan as a bridge to heart transplantation

Introducción y objetivos:El levosimendán ambulatorio repetitivo es una opción como puente al trasplante cardiaco (TxC), aunque la evidencia sobre su eficacia y su seguridad es escasa. El objetivo del registro LEVO-T es describir a los pacientes en lista de TxC que reciben levosimendán, sus pautas y los eventos clínicos durante el seguimiento, en comparación con los que no lo reciben. Métodos: Se revisó en retrospectiva a los pacientes en lista de espera para TxC electivo de 14 centros españoles desde 2015 hasta 2020. Resultados: Se incluyó a 1.015 pacientes consecutivos; los 238 (23,4%) que recibieron levosimendán mostraron más ingresos por insuficiencia cardiaca (IC) el año anterior y peor perfil clínico. Las dosis fijas por necesidades clínicas fueron la pauta más frecuente. Dos pacientes (0,8%) presentaron arritmias ventriculares no mortales. No hubo diferencias en hospitalizaciones por IC entre los que comenzaron levosimendán en los primeros 30 días después de inclusión y los que no (el 33,6 frente al 34,5%; p=0,848). De estos últimos, 102 (32,9%) pasaron a levosimendán después de un ingreso por IC, y la tasa de ingresos por IC/mes varió de 0,57 antes del levosimendán a 0,21 después. El análisis mediante emparejamiento por puntuación de propensión no mostró diferencias entre los pacientes con y sin levosimendán en la supervivencia a 1 año tras la inclusión en lista (HR=1,03; IC95%, 0,36-2,97; p=0,958) ni en la supervivencia tras el TxC (HR=0,97; IC95%, 0,60-1,56; p=0,958). Conclusiones: El levosimendán ambulatorio repetitivo como puente al trasplante cardiaco es un tratamiento frecuente y seguro que podría reducir ingresos por IC. (AU)

Introduction and objectives: Repetitive ambulatory doses of levosimendan are an option as a bridge to heart transplantation (HT), but evidence regarding the safety and efficacy of this treatment is scarce. The objective of the LEVO-T Registry is to describe the profile of patients on the HT list receiving levosimendan, prescription patterns, and clinical outcomes compared with patients not on levosimendan. Methods: We retrospectively reviewed all patients listed for elective HT from 2015 to 2020 from 14 centers in Spain. Results: A total of 1015 consecutive patients were included, of whom 238 patients (23.4%) received levosimendan. Patients treated with levosimendan had more heart failure (HF) admissions in the previous year and a worse clinical profile. The most frequent prescription pattern were fixed doses triggered by the patients’ clinical needs. Nonfatal ventricular arrhythmias occurred in 2 patients (0.8%). No differences in HF hospitalizations were found between patients who started levosimendan in the first 30 days after listing and those who did not (33.6% vs 34.5%; P=.848). Among those who did not, 102 patients (32.9%) crossed over to levosimendan after an HF admission. These patients had a rate of 0.57 HF admissions per month before starting levosimendan and 0.21 afterwards. Propensity score matching analysis showed no differences in survival at 1 year after listing between patients receiving levosimendan and those who did not (HR, 1.03; 95%CI, 0.36-2.97; P=.958) or in survival after HT (HR, 0.97; 95%CI, 0.60-1.56; P=.958). Conclusions: Repetitive levosimendan in an ambulatory setting as a bridge to heart transplantation is commonly used, is safe, and may reduce HF hospitalizations. (AU)

Pronóstico del trasplante cardiaco en pacientes con miocardiopatía hipertrófica y restrictiva. Análisis de un registro nacional / Prognosis after heart transplant in patients with hypertrophic and restrictive cardiomyopathy. A nationwide registry analysis

Introducción y objetivos: Existe controversia acerca de los resultados del trasplante cardiaco en pacientes con miocardiopatía hipertrófica (MCH) o restrictiva (MCR). Métodos: Análisis retrospectivo de receptores adultos de un primer trasplante cardiaco entre 1984 y 2021 incluidos en un registro nacional. La mortalidad al primer y quinto año postrasplante en receptores con MCH y MCR se comparó con la de receptores con miocardiopatía dilatada (MCD). Resultados: Se incluyó a 3.703 pacientes (3.112 MCD; 331 MCH y 260 MCR) con seguimiento mediano de 5,0 años (3,1-5,0). En comparación con la MCD, el riesgo ajustado de mortalidad a 1 año fue: MCH: hazard ratio (HR)=1,38; intervalo de confianza del 95% (IC95%), 1,07-1,78; p=0,01, MCR: HR=1,48; IC95%, 1,14-1,93; p=0,003. El riesgo ajustado a 5 años fue: MCH: HR=1,17; IC95%, 0,93-1,47; p=0,18; MCR: HR=1,52; IC95%, 1,22-1,89; p<0,001. En los últimos 20 años, la MCR mejoró significativamente la supervivencia a 1 año (R2 ajustada=0,95) y a 5 años (R2=0,88); la MCH mejoró la supervivencia a 5 años (R2=0,59) y a 1 año permaneció estable (R2=0,16). Conclusiones: Se asoció la MCR y la MCH a peor pronóstico precoz postrasplante que la MCD. La diferencia desfavorable se mantuvo para la supervivencia a 5 años solo para la MCR. Se observa una tendencia temporal a mejor pronóstico precoz y tardío para la MCR, y solo para el tardío en la MCH. (AU)

Introduction and objectives: Posttransplant outcomes among recipients with a diagnosis of hypertrophic cardiomyopathy (HCM) or restrictive cardiomyopathy (RCM) remain controversial. Methods: Retrospective analysis of a nationwide registry of first-time recipients undergoing isolated heart transplant between 1984 and 2021. One-year and 5-year mortality in recipients with HCM and RCM were compared with those with dilated cardiomyopathy (DCM). Results: We included 3703 patients (3112 DCM; 331 HCM; 260 RCM) with a median follow-up of 5.0 [3.1-5.0] years. Compared with DCM, the adjusted 1-year mortality risk was: HCM: HR, 1.38; 95%CI, 1.07-1.78; P=.01, RCM: HR, 1.48; 95%CI, 1.14-1.93; P=.003. The adjusted 5-year mortality risk was: HCM: HR, 1.17; 95%CI, 0.93-1.47; P=.18; RCM: HR, 1.52; 95%CI, 1.22-1.89; P<.001. Over the last 20 years, the RCM group showed significant improvement in 1-year survival (adjusted R2=0.95) and 5-year survival (R2=0.88); the HCM group showed enhanced the 5-year survival (R2=0.59), but the 1-year survival remained stable (R2=0.16). Conclusions: Both RCM and HCM were linked to a less favorable early posttransplant prognosis compared with DCM. However, at the 5-year mark, this unfavorable difference was evident only for RCM. Notably, a substantial temporal enhancement in both early and late mortality was observed for RCM, while for HCM, this improvement was mainly evident in late mortality. (AU)

Evolución nutricional durante las primeras etapas del trasplante de precursores hematopoyéticos: importancia del ángulo de fase / Nutritional evolution during the early stages of hematopoietic stem cell transplantation: importance of the phase angle

Introducción: el objetivo de este estudio es comparar los cambios en la antropometría, dinamometría e indicadores de la impedancia bioeléctrica (BIA) de pacientes sometidos a trasplante de precursores hematopoyéticos (TPH) autólogo y alogénico luego del periodo de acondicionamiento y una semana postrasplante, así como evaluar si estos cambios precoces se asocian con el desarrollo de complicaciones posteriores. Metodología: estudio de cohorte prospectivo. El estado nutricional se evaluó mediante antropometría, dinamometría y BIA en tres momentos diferentes definidos: T1, momento del ingreso; T2, después del periodo de acondicionamiento mieloablativo; y T3, día + 8 post-TPH. Resultados: un total de 40 pacientes fueron evaluados, 17 recibieron TPH autólogo (TAU) y 23, TPH alogénico (TAL). Los pacientes con TAL presentaron una mayor mortalidad y estadía hospitalaria en comparación con los pacientes con TAU. Aquellos que desarrollaron enfermedad injerto contra huésped (EICH) presentan un menor ángulo de fase (AF) que aquellos que no desarrollaron esta complicación (T2: AF TAL con EICH 4,8° vs. AF TAL sin EICH 5,5°, p = 0,007). Los pacientes que fallecieron durante la estadía hospitalaria son todos del grupo TAL y tenían un AF menor a 5° en T3. Peso, índice de masa corporal (IMC) e índice de masa libre de grasa (IMLG) no mostraron un impacto significativo y todos ellos estaban influidos por el agua corporal total. Conclusiones: la evaluación nutricional precoz de estos pacientes mediante AF parece prometedora, ya que no se ve alterado por la retención de agua y se puede evaluar antes que los cambios antropométricos sucedan.(AU)

Introduction: the aim of this study is to compare the changes in anthropometry, dynamometry and bioelectrical impedance analysis (BIA) of patients undergoing autologous and allogeneic hematopoietic stem cell transplantation (HSCT) after the conditioning period and one-week post-transplantation, and to assess whether these early changes are associated with the development of later complications. Methods: prospective cohort study. Nutritional status was assessed by anthropometry, dynamometry and BIA at three different defined times: T1, time of admission; T2, after the myeloablative conditioning period; and T3, day + 8 post-HSCT.Results: forty patients were evaluated, 17 received autologous HSCT (TAU) and 23 received allogeneic HSCT (TAL). Patients with TAL had higher mortality and hospital stay compared to patients with TAU. Those who developed graft versus host disease (GVHD) presented a lower phase angle (PA) than those who did not develop this complication (T2: TAL PA with GVHD 4.8° vs TAL PA without GVHD 5.5°, p = 0.007). The patients who died during the hospital stay are all from the TAL group and had PA less than 5° at T3. Weight, body mass index (BMI) and fat-free mass index (FMI) did not show a significant impact, and all of them were influenced by total body water. Conclusions: early nutritional evaluation of these patients by phase angle seems promising, since it is not altered by water retention and can be evaluated before anthropometric changes occur.(AU)

Influencia de la adaptación dietética individualizada en pacientes sometidos atrasplante de precursores hematopoyéticos / Estudio aDiTraS Infl uence of individualized dietary adaptation in patients undergoing hematopoietic stem cell transplantation. The ADITRAS study

Introducción: el objetivo del estudio fue valorar la eficacia de una adaptación dietética individualizada para conseguir los requerimientos nutricionales en pacientes sometidos a trasplante de precursores hematopoyéticos (TPH). Metodología: estudio piloto de intervención nutricional con pacientes sometidos a TPH. Se realizó una valoración nutricional en las primeras 24 horas de ingreso y cada 48 a 72 horas hasta el alta, o + 40 días del trasplante, realizando adaptaciones dietéticas. Resultados: se reclutaron 25 pacientes. Según el MUST, el 92,0 % (n = 23) se encontraban bien nutridos en la visita inicial, con una pérdida de 2,1 (3,8) kg y un IMC de 26,4 kg/m2 (4,2). Antes del TPH ya hubo una disminución de la ingesta del 15,4 (23,5) % y del peso corporal de 0,2 (3,2) kg; tras el TPH, la pérdida de peso fue de 3,4 (5,0) kg y la disminución de la ingesta del 6,5 (30,4) %. Los síntomas predominantes fueron mucositis (60 %), náuseas (60 %) y diarrea (44 %). Se adaptó la dieta en el 100 % de los pacientes y el 52 % recibieron soporte nutricional oral (SNO) (n = 13), mientras que la nutrición enteral (NE) y la nutrición parenteral (NP) se utilizaron solo 1 vez. Conclusión: el estado nutricional de los pacientes sometidos a TPH es normal al ingreso pero se deteriora durante la realización del trasplante y su acondicionamiento previo. La intervención dietética es clave para mantener la ingesta oral y disminuir el riesgo de desnutrición.(AU)

Introduction: the objective of the study was to assess the effi cacy of an individualized dietary adaptation to achieve nutritional requirements in patients undergoing hematopoietic stem cell transplantation (HSCT). Methodology: a pilot study of a nutritional intervention in patients undergoing HSCT. A nutritional assessment was performed the fi rst 24 hours of admission and every 48-72 hours until discharge, or + 40 days after the transplant, making dietary adaptations. Results: 25 patients were recruited. According to MUST, 92.0 % (n = 23) were well nourished at the initial visit, with a loss of 2.1 (3.8) kg and a BMI of 26.4 kg/m2 (4.2). Before HSCT, there was already a decrease in intake of 15.4 (23.5) % and in body weight of 0.2 (3.2) kg; after the HSCT, the weight loss was 3.4 (5.0) kg and the decrease in intake was 6.5 (30.4) %. The predominant symptoms were mucositis (60 %), nausea (60 %), and diarrhea (44 %). The diet was adapted in 100 % of the patients, 52 % received oral nutritional support (ONS) (n = 13); enteral nutrition (EN) and parenteral nutrition (PN) were used only once. Conclusion: the nutritional status of patients undergoing HSCT is normal on admission but deteriorates during transplantation and prior conditioning. Dietary intervention is key to maintaining oral intake and reducing the risk of malnutrition.(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)

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.

Randomized clinical trial of non-antibiotic prophylaxis with d-Mannose plus Proanthocyanidins vs. Proanthocyanidins alone for urinary tract infections and asymptomatic bacteriuria in de novo kidney transplant recipients: The Manotras study.

BACKGROUND: Studies analyzing non-antibiotic alternatives in kidney transplant UTI's are lacking. d-Mannose, a simple sugar, inhibits bacterial attachment to the urothelium, as does Proanthocyanidins; both could act as a synergic strategy preventing UTI; nonetheless their efficacy and safety have not been evaluated in kidney transplant population yet. METHODS: This is a pilot prospective, double-blind randomized trial. Sixty de novo kidney transplant recipients were randomized (1:1) to receive a prophylactic strategy based on a 24-h prolonged release formulation of d-Mannose plus Proanthocyanidins vs. Proanthocyanidins (PAC) alone. The supplements were taken for the first 3 months after kidney transplant and then followed up for 3 months as well. The main objective of the study was to search if the addition of Mannose to PAC alone reduced the incidence of UTI and/or asymptomatic bacteriuria in the first 6 months post-transplantation. RESULTS: 27% of patients experienced one UTI episode (cystitis or pyelonephritis) while asymptomatic bacteriuria was very common (57%). Incidences according UTI type or AB were: 7% vs. 4% for cystitis episode (p 0.3), 4% vs. 5% for pyelonephritis (p 0.5) and 17% vs. 14% for asymptomatic bacteriuria (p 0.4) for patients in the Mannose+PAC group vs. PAC group respectively. The most frequent bacteria isolated in both groups was Escherichia coli (28% of all episodes), UTI or AB due to E. coli was not different according to study group (30% vs. 23% for Mannose+PAC vs. PAC alone p 0.37). CONCLUSIONS: Non-antibiotic therapy is an unmet need to prevent UTI after kidney transplantation; however, the use of d-Mannose plus PAC does not seem capable to prevent it.

El trasplante de córnea en Villa Clara: diez años transcurridos de la primera intervención quirúrgica / Corneal transplantation in Villa Clara: after ten years the first surgical intervention

Introducción: La córnea constituye el elemento más importante del sistema óptico, al ser el primer medio transparente del ojo; tiene la finalidad de mejorar la calidad de la imagen que se forma en la retina, por lo que su transparencia es imprescindible para poder obtener una buena agudeza visual. Cuando sus capas están afectadas por diferentes enfermedades, se requiere sustituir este tejido dañado; este procedimiento, denominado trasplante de córnea o queratoplastia, tiene diferentes finalidades. Objetivo: Caracterizar los resultados de la cirugía de trasplante de córnea tras diez años del primer procedimiento quirúrgico en la provincia de Villa Clara. Métodos: Se realizó un estudio observacional descriptivo longitudinal retrospectivo, con una muestra de 204 pacientes operados de trasplante de córnea en el Hospital Universitario Clínico-Quirúrgico «Arnaldo Milián Castro» de Villa Clara, en el período comprendido entre 2008 y 2018. Las variables estudiadas fueron: sexo, finalidad del procedimiento, diagnóstico y complicaciones. Resultados: Predominó el sexo masculino (53,4 %); la finalidad más frecuente del trasplante tuvo fines ópticos (85,8 %); principal diagnóstico: la queratopatía bullosa (42,7 %); dentro de las complicaciones más frecuentes estuvieron: el rechazo al injerto, el defecto epitelial y el glaucoma secundario. Conclusiones: La cirugía de trasplante de córnea en la provincia de Villa Clara significa un gran avance en el desarrollo y perfeccionamiento para el tratamiento de múltiples afecciones corneales. Los diagnósticos más frecuentes fueron: la queratopatía bullosa y las opacidades corneales; las complicaciones más frecuentes, el rechazo al injerto, la aparición de defectos epiteliales y el glaucoma secundario.

Introduction: the cornea constitutes the most important element of the optical system, being the first transparent medium of the eye; its purpose is to improve the quality of the image that is formed on the retina, so its transparency is essential to obtain good visual acuity. When its layers are affected by different diseases, it is required to replace this damaged tissue; this procedure called cornea transplant or keratoplasty has different purposes. Objective: to characterize the results of corneal transplant surgery ten years after the first surgical procedure in Villa Clara province. Methods: a retrospective, longitudinal, descriptive and observational study was carried out with a sample of 204 patients who underwent corneal transplant surgery at "Arnaldo Milián Castro" Clinical and Surgical University Hospital in Villa Clara between 2008 and 2018. Age, purpose of the procedure, diagnosis and complications were the variables studied. Results: male gender predominated (53.4%); the most frequent purpose of the transplant was for optical purposes (85.8%); bullous keratopathy (42.7%) was the main diagnosis as well as, graft rejection, epithelial defect and secondary glaucoma were among the most frequent complications. Conclusions: corneal transplant surgery in Villa Clara province means a great advance in the development and improvement for the treatment of multiple corneal conditions. The most frequent diagnoses were bullous keratopathy and corneal opacities; graft rejection, the appearance of epithelial defects and secondary glaucoma were the most frequent complications.