Multi-Modality Imaging in the Assessment of Cardiovascular Toxicity in the Cancer Patient

Cancer therapy can be associated with both cardiac and vascular toxicity. Advanced multi-modality imaging can be used to stratify patient risk, identify cardiovascular injury during and after therapy, and forecast recovery. Echocardiography continues to be the mainstay in the evaluation of cardiac toxicity. Particularly, echocardiography-based strain imaging is useful for risk stratification of patients at baseline, and detection of subclinical left ventricle (LV) dysfunction during therapy. Cardiac magnetic resonance (CMR) serves a complementary role in the patient with poor echocardiographic or equilibrium radionuclide angiographic image quality or in situations where a more accurate and precise LV ejection fraction measurement is needed to inform decisions regarding discontinuation of chemotherapy. New CMR techniques like T1 and T2 mapping and positron emission tomography (PET) imaging will help us better understand the structural, pathological, and metabolic myocardial changes associated with ventricular dysfunction or release of serum biomarkers. CMR may also be helpful in the evaluation of vascular complications of cancer therapy. Stress echocardiography, stress CMR, computed tomography, and PET are excellent imaging options in the evaluation of ischemia in patients receiving therapies that could potentially cause vasospasm or accelerated atherosclerosis

Magnetic Resonance Imaging to Detect Cardiovascular Effects of Cancer Therapy:JACC CardioOncology State-of-the-Art Review

peer reviewedThis paper aims to empower and inform cardio-oncologists by providing a practical guide to the clinical application of cardiac magnetic resonance (CMR) in the rapidly evolving field of cardio-oncology. Specifically, we describe how CMR can be used to assess the cardiovascular effects of cancer therapy. The CMR literature, relevant societal guidelines, indication-specific imaging protocols, and methods to overcome some of the challenges encountered in performing and accessing CMR are reviewed

Integración del aprendizaje social (social learning) en las asignatras vinculadas al campo de conocimiento del Derecho del Trabajo y la Seguridad Social

Este proyecto trata de integrar las redes sociales como una herramienta colaborativa en la docencia de las materias relacionadas con el Derecho del Trabajo. De entre los recursos asociados a las plataformas "b-learning", e empleo de las redes sociales permite el intercambio de información en tiempo real. A través de este instrumento, los alumnos, guiados por el profesor, aportan su trabajo activo en relación con la materia seleccionada y poniéndolo en común mediante la herramienta elegida. En este proyecto nos decantamos por el empleo de Facebook. Esta metodología puede ser aplicada en cuantas disciplinas se vean especialmente vinculadas a la realidad económico-social, que por su naturaleza requieran de una permanente actualización. La recepción de esta metodología es evidente en aquellas materias que exijan del alumno un esfuerzo crítico que le permita acercarse en profundidad a los elementos novedosos de la materia

Toward a new clinical classification of patients with familial hypercholesterolemia: One perspective from Spain

The introduction of singular therapies, such as proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i), to lower high cholesterol levels requires better classification of patients eligible for intensive lipid lowering therapy. According to the European Medicines Administration, PCSK9i are recommended in primary prevention in familial hypercholesterolemia (FH) patients. Therefore, an FH diagnosis is not simply an academic issue, because it has many clinical implications. The bases of a diagnosis of FH are not entirely clear. The availability of genetic testing, including large genome-wide association analyses and whole genome studies, has shown that some patients with a clinical diagnosis of definite FH have no mutations in the genes associated with the disease. This fact does not exclude the very high cardiovascular risk of these patients, and an early and intensive lipid lowering therapy is recommended in all FH patients. Because an FH diagnosis is a cornerstone for decisions about therapies, a precise definition of FH is urgently required. This is an expert consensus document from the Spanish Atherosclerosis Society. We propose the following classification: familial hypercholesterolemia syndrome integrated by (1) heterozygous familial hypercholesterolemia: patients with clinically definite FH and a functional mutation in one allele of the LDLR, ApoB:100, and PCSK9 genes; (2) homozygous familial hypercholesterolemia: mutations affect both alleles; (3) polygenic familial hypercholesterolemia: patients with clinically definite FH but no mutations associated with FH are found (to be distinguished from non-familial, multifactorial hypercholesterolemia); (4) familial hypercholesterolemia combined with hypertriglyceridemia: a subgroup of familial combined hyperlipidaemia patients fulfilling clinically definite FH with associated hypertriglyceridemia

Safety and vaccine-induced HIV-1 immune responses in healthy volunteers following a late MVA-B boost 4 years after the last immunization

Background: We have previously shown that an HIV vaccine regimen including three doses of HIV-modified vaccinia virus Ankara vector expressing HIV-1 antigens from clade B (MVA-B) was safe and elicited moderate and durable (1 year) T-cell and antibody responses in 75% and 95% of HIV-negative volunteers (n = 24), respectively (RISVAC02 study). Here, we describe the long-term durability of vaccine-induced responses and the safety and immunogenicity of an additional MVA-B boost. Methods: 13 volunteers from the RISVAC02 trial were recruited to receive a fourth dose of MVA-B 4 years after the last immunization. End-points were safety, cellular and humoral immune responses to HIV-1 and vector antigens assessed by ELISPOT, intracellular cytokine staining (ICS) and ELISA performed before and 2, 4 and 12 weeks after receiving the boost. Results: Volunteers reported 64 adverse events (AEs), although none was a vaccine-related serious AE. After 4 years from the 1st dose of the vaccine, only 2 volunteers maintained low HIV-specific T-cell responses. After the late MVA-B boost, a modest increase in IFN-γ T-cell responses, mainly directed against Env, was detected by ELISPOT in 5/13 (38%) volunteers. ICS confirmed similar results with 45% of volunteers showing that CD4+ T-cell responses were mainly directed against Env, whereas CD8+ T cell-responses were similarly distributed against Env, Gag and GPN. In terms of antibody responses, 23.1% of the vaccinees had detectable Env-specific binding antibodies 4 years after the last MVA-B immunization with a mean titer of 96.5. The late MVA-B boost significantly improved both the response rate (92.3%) and the magnitude of the systemic binding antibodies to gp120 (mean titer of 11460). HIV-1 neutralizing antibodies were also enhanced and detected in 77% of volunteers. Moreover, MVA vector-specific T cell and antibody responses were boosted in 80% and 100% of volunteers respectively. Conclusions: One boost of MVA-B four years after receiving 3 doses of the same vaccine was safe, induced moderate increases in HIV-specific T cell responses in 38% of volunteers but significantly boosted the binding and neutralizing antibody responses to HIV-1 and to the MVA vector

Fine tuning the extracellular environment accelerates the derivation of kidney organoids from human pluripotent stem cells

The generation of organoids is one of the biggest scientific advances in regenerative medicine. Here, by lengthening the time that human pluripotent stem cells (hPSCs) were exposed to a three-dimensional microenvironment, and by applying defined renal inductive signals, we generated kidney organoids that transcriptomically matched second-trimester human fetal kidneys. We validated these results using ex vivo and in vitro assays that model renal development. Furthermore, we developed a transplantation method that utilizes the chick chorioallantoic membrane. This approach created a soft in vivo microenvironment that promoted the growth and differentiation of implanted kidney organoids, as well as providing a vascular component. The stiffness of the in ovo chorioallantoic membrane microenvironment was recapitulated in vitro by fabricating compliant hydrogels. These biomaterials promoted the efficient generation of renal vesicles and nephron structures, demonstrating that a soft environment accelerates the differentiation of hPSC-derived kidney organoids

Safety and immunogenicity of a modified pox vector-based HIV/AIDS vaccine candidate expressing Env, Gag, Pol and Nef proteins of HIV-1 subtype B (MVA-B) in healthy HIV-1-uninfected volunteers: A phase I clinical trial (RISVAC02)

Clinical Trial, Phase ITo investigate the safety and immunogenicity of a modified vaccinia virus Ankara vector expressing HIV-1 antigens from clade B (MVA-B), a phase-I, doubled-blind placebo-controlled trial was performed.Peer reviewe