Burden and challenges of heart failure in patients with chronic kidney disease. A call to action

Patients with the dual burden of chronic kidney disease (CKD) and chronic congestive heart failure (HF) experience unacceptably high rates of symptom load, hospitalization, and mortality. Currently, concerted efforts to identify, prevent and treat HF in CKD patients are lacking at the institutional level, with emphasis still being placed on individual specialty views on this topic. The authors of this review paper endorse the need for a dedicated cardiorenal interdisciplinary team that includes nephrologists and renal nurses and jointly manages appropriate clinical interventions across the inpatient and outpatient settings. There is a critical need for guidelines and best clinical practice models from major cardiology and nephrology professional societies, as well as for research funding in both specialties to focus on the needs of future therapies for HF in CKD patients. The implementation of crossspecialty educational programs across all levels in cardiology and nephrology will help train future specialists and nurses who have the ability to diagnose, treat, and prevent HF in CKD patients in a precise, clinically effective, and cost-favorable manner.Los pacientes con enfermedad renal crónica (ERC) que desarrollan insuficiencia cardíaca (IC) congestiva crónica presentan cifras inaceptablemente altas de síntomas, hospitalización y mortalidad. Actualmente, se echan en falta iniciativas institucionales dirigidas a identificar, prevenir y tratar la IC en los pacientes con ERC de manera multidisciplinar, prevaleciendo las actuaciones de las especialidades individuales. Los autores de este artículo de revisión respaldan la necesidad de crear equipos multidisciplinares cardiorrenales, en los que participen nefrólogos y enfermeras renales, que gestionen colaborativamente las intervenciones clínicas apropiadas en los entornos de pacientes con ERC e IC hospitalizados y ambulatorios. Es necesario y urgente que se elaboren guías y modelos de práctica clínica sobre la ERC con IC por parte de las sociedades profesionales de cardiología y nefrología, así como financiación para la investigación concertada entre ambas especialidades sobre la necesidad de futuros tratamientos para la IC en pacientes con ERC. La implementación de programas educativos cardiorrenales a todos los niveles en cardiología y nefrología ayudará a formar a los futuros especialistas y enfermeras para que tengan la capacidad de diagnosticar, tratar y prevenir la IC en pacientes con ERC de manera precisa, clínicamente efectiva y económicamente favorabl

COVID-19 Severity and Survival over Time in Patients with Hematologic Malignancies: A Population-Based Registry Study

Mortality rates for COVID-19 have declined over time in the general population, but data in patients with hematologic malignancies are contradictory. We identified independent prognostic factors for COVID-19 severity and survival in unvaccinated patients with hematologic malignancies, compared mortality rates over time and versus non-cancer inpatients, and investigated post COVID-19 condition. Data were analyzed from 1166 consecutive, eligible patients with hematologic malignancies from the population-based HEMATO-MADRID registry, Spain, with COVID-19 prior to vaccination roll-out, stratified into early (February–June 2020; n = 769 (66%)) and later (July 2020–February 2021; n = 397 (34%)) cohorts. Propensity-score matched non-cancer patients were identified from the SEMI-COVID registry. A lower proportion of patients were hospitalized in the later waves (54.2%) compared to the earlier (88.6%), OR 0.15, 95%CI 0.11–0.20. The proportion of hospitalized patients admitted to the ICU was higher in the later cohort (103/215, 47.9%) compared with the early cohort (170/681, 25.0%, 2.77; 2.01–3.82). The reduced 30-day mortality between early and later cohorts of non-cancer inpatients (29.6% vs. 12.6%, OR 0.34; 0.22–0.53) was not paralleled in inpatients with hematologic malignancies (32.3% vs. 34.8%, OR 1.12; 0.81–1.5). Among evaluable patients, 27.3% had post COVID-19 condition. These findings will help inform evidence-based preventive and therapeutic strategies for patients with hematologic malignancies and COVID-19 diagnosis.Depto. de MedicinaFac. de MedicinaTRUEFundación Madrileña de Hematología y HemoterapiaFundación Leucemia y LinfomaAsociación Madrileña de Hematología y Hemoterapiapu

Dietary diversity and Depression: Cross-sectional and longitudinal analyses in Spanish adult population with Metabolic Syndrome. Findings from PREDIMED-PLUS Trial.

Objective: To examine the cross-sectional and longitudinal (2-year follow-up) associations between Dietary Diversity (DD) and depressive symptoms. Design: An energy-adjusted Dietary Diversity Score (DDS) was assessed using a validated food-frequency questionnaire and was categorized into quartiles (Q). The variety in each food group was classified into 4 categories of diversity (C). Depressive symptoms were assessed with Beck Depression Inventory-II (Beck II) questionnaire and depression cases defined as physician-diagnosed or Beck II>=18. Linear and logistic regression models were used. Setting: Spanish older adults with Metabolic Syndrome. Participants: A total of 6625 adults aged (55-75 years) from the PREDIMED-Plus study with overweight or obesity and MetS. Results: Total DDS was inversely and statistically significantly associated with depression in the cross-sectional analysis conducted; Odds Ratio (OR) Q4 vs Q1= 0.76 (95% confidence interval (CI): 0.64, 0.90). This was driven by high diversity compared to low diversity (C3 vs. C1) of vegetables [OR (95%CI) = 0.75 (0.57, 0.93)], cereals [OR (95%CI) = 0.72 (0.56-0.94)] and proteins [OR (95%CI) = 0.27 (0.11, 0.62)]. In the longitudinal analysis, there was no significant association between the baseline DDS and changes in depressive symptoms after 2 y- of follow-up, except for DD in vegetables C4 vs C1= [β (95%CI) = 0.70 (0.05, 1.35)]. Conclusions: According to our results, DD is associated with the presence of depressive symptoms but eating more diverse does not seem to reduce the risk of future depression. Additional longitudinal studies (with longer follow-up period) are needed to confirm these findings

Identification of candidate Parkinson disease genes by integrating genome-wide association study, expression, and epigenetic data sets

Importance Substantial genome-wide association study (GWAS) work in Parkinson disease (PD) has led to the discovery of an increasing number of loci shown reliably to be associated with increased risk of disease. Improved understanding of the underlying genes and mechanisms at these loci will be key to understanding the pathogenesis of PD. Objective To investigate what genes and genomic processes underlie the risk of sporadic PD. Design and Setting This genetic association study used the bioinformatic tools Coloc and transcriptome-wide association study (TWAS) to integrate PD case-control GWAS data published in 2017 with expression data (from Braineac, the Genotype-Tissue Expression [GTEx], and CommonMind) and methylation data (derived from UK Parkinson brain samples) to uncover putative gene expression and splicing mechanisms associated with PD GWAS signals. Candidate genes were further characterized using cell-type specificity, weighted gene coexpression networks, and weighted protein-protein interaction networks. Main Outcomes and Measures It was hypothesized a priori that some genes underlying PD loci would alter PD risk through changes to expression, splicing, or methylation. Candidate genes are presented whose change in expression, splicing, or methylation are associated with risk of PD as well as the functional pathways and cell types in which these genes have an important role. Results Gene-level analysis of expression revealed 5 genes (WDR6 [OMIM 606031], CD38 [OMIM 107270], GPNMB [OMIM 604368], RAB29 [OMIM 603949], and TMEM163 [OMIM 618978]) that replicated using both Coloc and TWAS analyses in both the GTEx and Braineac expression data sets. A further 6 genes (ZRANB3 [OMIM 615655], PCGF3 [OMIM 617543], NEK1 [OMIM 604588], NUPL2 [NCBI 11097], GALC [OMIM 606890], and CTSB [OMIM 116810]) showed evidence of disease-associated splicing effects. Cell-type specificity analysis revealed that gene expression was overall more prevalent in glial cell types compared with neurons. The weighted gene coexpression performed on the GTEx data set showed that NUPL2 is a key gene in 3 modules implicated in catabolic processes associated with protein ubiquitination and in the ubiquitin-dependent protein catabolic process in the nucleus accumbens, caudate, and putamen. TMEM163 and ZRANB3 were both important in modules in the frontal cortex and caudate, respectively, indicating regulation of signaling and cell communication. Protein interactor analysis and simulations using random networks demonstrated that the candidate genes interact significantly more with known mendelian PD and parkinsonism proteins than would be expected by chance. Conclusions and Relevance Together, these results suggest that several candidate genes and pathways are associated with the findings observed in PD GWAS studies

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Assessment of the Gender Variable: CFNI in Chilean Women

The aim of this study was to analyze the factor structure and the internal consistency of the Conformity to Feminine Gender Norms Inventory - CFNI in the Chilean women. The research was conducted with 308 women between 18 and 50 years of age. Factor analysis revealed a similar profile to that obtained in the USA, it supports the structure proposed by the authors. Taking these results into account, we concluded that the CFNI is a good operationalization of the variable gender and it can be applied to Chilean women in future studies.El objetivo de este estudio fue analizar la estructura factorial y la consistencia interna de las puntuaciones del Inventario de Conformidad con las Normas de Género Femeninas (CFNI) en mujeres chilenas. La investigación se llevó a cabo con 308 mujeres, entre 18 y 50 años de edad. El análisis factorial reveló un perfil similar al obtenido en EEUU, por lo que es compatible con la estructura propuesta por los autores. Teniendo en cuenta estos resultados, se concluyó que el CFNI es una buena operativización de la variable género y podrá ser utilizado en futuras investigaciones con mujeres chilenas

La enseñanza de la estructura organizativa a través del Método del Caso

Teaching at university level has evolved in recent years towards teaching methodologies in which the student has an increasingly active role in their learning, being the protagonist together with the teaching staff. The use of techniques in which students put into practice and reflect on the theoretical contents has benefits both for the acquisition of knowledge and for the development of competences. In the field of business administration, business reality is a continuous source of information for putting this type of methodology into practice. Therefore, the objective of this paper is to achieve, through the case method, that the students of the subject " Organizational Structure and Behavior" of the degree in Business Administration and Management assimilate, understand and put into practice the concepts acquired in the theoretical classes, favoring autonomous learning, cooperative learning, dialogue and peer learning. Specifically, lectures have been replaced by a set of individual and group activities around a business case study designed by the teaching staff. The use of the case method has been adequate to achieve the objectives set at the beginning of the activity. Students have expressed a high satisfaction with the learning process, a higher perceived quality of learning, and increase of digital competences and an improvement of the evaluation processes. In addition, this methodology has increased their interest in the subject and its contents and has improved their autonomy in the learning process.La docencia en el ámbito universitario ha evolucionado en los últimos años hacia metodologías de enseñanza en las que el estudiante tiene un rol cada vez más activo en su aprendizaje y es protagonista del mismo junto con el profesorado. El uso de técnicas en las que los estudiantes ponen en práctica y reflexionan sobre los contenidos teóricos tiene beneficios tanto para la adquisición de conocimientos, como para el desarrollo de competencias. En el ámbito de la administración de empresas, la realidad empresarial es una fuente continua de información para poner en práctica este tipo de metodologías. Por ello, el objetivo del presente trabajo es conseguir, a través de la metodología del caso, que el alumnado de la asignatura de ?Estructura y Comportamiento Organizativo? del grado en Administración y Dirección de Empresas asimile, comprenda y ponga en práctica los conceptos adquiridos en las clases teóricas, favoreciendo el aprendizaje autónomo, el trabajo cooperativo, el diálogo y el aprendizaje entre iguales. En concreto, se han sustituido las lecciones magistrales por un conjunto de actividades individuales y grupales en torno a un caso de estudio empresarial diseñado por el profesorado. La metodología del caso ha resultado adecuada para alcanzar los objetivos planteados al inicio de la actividad. Los estudiantes han expresado una alta satisfacción con el proceso de aprendizaje, una mayor calidad del aprendizaje percibida, un incremento de las competencias digitales y una mejora de los procesos de evaluación. Además, esta metodología ha aumentado su interés por la asignatura y sus contenidos y ha mejorado su autonomía en el proceso de aprendizaje

Increased miR-7641 levels in peritoneal hyalinizing vasculopathy in long-term peritoneal dialysis patients

Peritoneal hyalinizing vasculopathy (PHV) represents the cornerstone of long-term peritoneal dialysis (PD), and especially characterizes patients associated with encapsulating peritoneal sclerosis. However, the mechanisms of PHV development remain unknown. A cross sectional study was performed in 100 non-selected peritoneal biopsies of PD patients. Clinical data were collected and lesions were evaluated by immunohistochemistry. In selected biopsies a microRNA (miRNA)-sequencing analysis was performed. Only fifteen patients (15%) showed PHV at different degrees. PHV prevalence was significantly lower among patients using PD fluids containing low glucose degradation products (GDP) (5.9% vs. 24.5%), angiotensin converting enzyme inhibitors (ACEIs) (7.5% vs. 23.4%), statins (6.5% vs. 22.6%) or presenting residual renal function, suggesting the existence of several PHV protective factors. Peritoneal biopsies from PHV samples showed loss of endothelial markers and induction of mesenchymal proteins, associated with collagen IV accumulation and wide reduplication of the basement membrane. Moreover, co-expression of endothelial and mesenchymal markers, as well as TGF-β1/Smad3 signaling activation were found in PHV biopsies. These findings suggest that an endothelial-to-mesenchymal transition (EndMT) process was taking place. Additionally, significantly higher levels of miR-7641 were observed in severe PHV compared to non-PHV peritoneal biopsies. Peritoneal damage by GDPs induce miRNA deregulation and an EndMT process in submesothelial vessels, which could contribute to collagen IV accumulation and PHV.This research was funded by grants from the Instituto de Salud Carlos III (ISCIII) and Fondos FEDER European Union (PI15/00120 to R.S, PI18/00882 to M.A.B, PI17/00119 to M.R.-O. and Red de Investigación Renal (REDINREN): RD16/0009, to R.S and M.R-O); “Convocatoria Dinamización Europa Investigación 2019” MINECO (EIN2019-103294 to M.R.-O.); IMPROVE-PD project (“Identification and Management of Patients at Risk–Outcome and Vascular Events in Peritoneal Dialysis”) funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie Grant Agreement No. 812699 to M.R.-O. and M.L-C. Spanish Ministry of Science and Innovation/Fondo Europeo de Desarrollo Regional (MICINN/FEDER) (PID2019-110132RB-I00) to M.L.-C.Peer reviewedPeer reviewe