Recombinant Klotho administration after myocardial infarction reduces ischaemic injury and arrhythmias by blocking intracellular calcium mishandling and CaMKII activation.

Ischaemic heart disease (IHD) remains a major cause of death and morbidity. Klotho is a well-known anti-ageing factor with relevant cardioprotective actions, at least when renal dysfunction is present, but its actions are much less known when renal function is preserved. This study investigated Klotho as a biomarker and potential novel treatment of IHD-associated complications after myocardial infarction (MI) under preserved renal function.

Comorbidities Associated With Different Degrees of Severity in Children and Young People Hospitalized With Acute COVID-19.

In this prospective cohort study with 2326 hospitalized children and young people with coronavirus disease 2019 in Spain and Colombia, 36.4% had comorbidities. Asthma, recurrent wheezing, chronic neurological, cardiac and pulmonary diseases significantly increased the risk of severe outcomes such as death, mechanical ventilation and intensive care unit admission.

Interleukin-6 as a prognostic marker in acute kidney injury and its klotho-dependent regulation.

Background And Objective: In acute kidney injury (AKI), a strong inflammatory component is activated in response to the renal damage, and one of the main mediators behind this process is the pro-inflammatory interleukin 6 or IL-6. Beside to this phenomenon, there are also alterations in different components of mineral metabolism, such as those dependent on fibroblast growth factor (FGF)23 and the anti-ageing cofactor klotho. The aim of this work was to explore the association between renal function and systemic levels of IL-6, as well as FGF23 and klotho in the early stages of AKI, analysing the predictive capacity of IL-6 in early mortality associated with AKI.

Connecting genomic and proteomic signatures of amyloid burden in the brain.

Background: Alzheimer's disease (AD) has a high heritable component characteristic of complex diseases, yet many of the genetic risk factors remain unknown. We combined genome-wide association studies (GWAS) on amyloid endophenotypes measured in cerebrospinal fluid (CSF) and positron emission tomography (PET) as surrogates of amyloid pathology, which may be helpful to understand the underlying biology of the disease.

Methods: We performed a meta-analysis of GWAS of CSF Aβ42 and PET measures combining six independent cohorts (n=2,076).

Complete vs Culprit-Only Revascularization in Older Patients With Myocardial Infarction With or Without ST-Segment Elevation.

Background: The effectiveness of complete revascularization is well established in patients with ST-segment elevation myocardial infarction (STEMI), but it is less investigated in those with non-ST-segment elevation myocardial infarction (NSTEMI).

Objectives: This study aimed to assess whether complete revascularization, compared with culprit-only revascularization, was associated with consistent outcomes in older patients with STEMI and NSTEMI.

Methods: In the FIRE (Functional Assessment in Elderly MI Patients with Multivessel Disease) trial, 1,445 older patients with myocardial infarction (MI) were randomized to culprit-only or physiology-guided complete revascularization, stratified by STEMI (n = 256 culprit-only vs n = 253 complete) and NSTEMI (n = 469 culprit-only vs n = 467 complete).

A genome-wide association meta-analysis of all-cause and vascular dementia.

Introduction: Dementia is a multifactorial disease with Alzheimer's disease (AD) and vascular dementia (VaD) pathologies making the largest contributions. Yet, most genome-wide association studies (GWAS) focus on AD.

Methods: We conducted a GWAS of all-cause dementia (ACD) and examined the genetic overlap with VaD.

Consensus document of the Spanish Society of Paediatric Infectious Diseases (SEIP) and the Spanish Society of Paediatric Intensive Care (SECIP) for the diagnosis and treatment of central venous catheter-related infections in paediatric care.

Intravascular devices are essential for the diagnostic and therapeutic approach to multiple diseases in paediatrics, and central venous catheters (CVCs) are especially important. One of the most frequent complications is the infection of these devices, which is associated with a high morbidity and mortality. These infections are highly complex, requiring the use of substantial resources, both for their diagnosis and treatment, and affect vulnerable paediatric patients admitted to high-complexity units more frequently.

Experience with the ACURATE neo and neo2 transcatheter aortic valves in Spain. The PRECISA (PRospective Evaluation Complementing Investigation with ACURATE devices) registry.

Background: Previous studies have documented a high rate of implantation success with the ACURATE neo2 valve, as well as a reduction in paravalvular leak (PVL) compared to its predecessor, the ACURATE neo. However, there are no studies that have reviewed and compared the long-term clinical and hemodynamic outcomes of these patients.

Aims: This study aimed to evaluate the results of the ACURATE neo transcatheter aortic valve in a real-world context, and to compare the results of the outcomes of both generations of this device (ACURATE neo and ACURATE neo2), with a specific focus on procedural success, safety, and long-term effectiveness.

PAH deficient pathology in humanized c.1066-11G>A phenylketonuria mice.

We have generated using CRISPR/Cas9 technology a partially humanized mouse model of the neurometabolic disease phenylketonuria (PKU), carrying the highly prevalent PAH variant c.1066-11G>A. This variant creates an alternative 3' splice site, leading to the inclusion of 9 nucleotides coding for 3 extra amino acids between Q355 and Y356 of the protein.

Violence as a Health Problem.

Violence is a public health problem, and when it affects childhood, it can cause illness throughout the individual's life. Apart from being able to cause damage in the physical, mental and social spheres, it represents a violation of the rights of the affected children, and a high consumption of resources, both economic and social. A multitude of investigations have improved attention to this violence.

Phase II trial of afatinib in patients with advanced urothelial carcinoma with genetic alterations in ERBB1-3 (LUX-Bladder 1).

Background: Preclinical and early clinical data suggest that the irreversible ErbB family blocker afatinib may be effective in urothelial cancers harbouring ERBB mutations.

Methods: This open-label, phase II, single-arm trial (LUX-Bladder 1, NCT02780687) assessed the efficacy and safety of second-line afatinib 40 mg/d in patients with metastatic urothelial carcinoma with ERBB1-3 alterations. The primary endpoint was 6-month progression-free survival rate (PFS6) (cohort A); other endpoints included ORR, PFS, OS, DCR and safety (cohorts A and B).

Ocular side effects of oncological therapies: Review.

With the advance of cancer therapy in recent years, the knowledge of the mechanisms involved in this disease has increased, which has meant an increase in the quality of life and survival of patients with tumor pathologies previously considered incurable or refractory to treatment. The number of drugs used has increased exponentially in number, and although the implicit toxicity is lower than that of conventional antineoplastic therapy, they lead to the appearance of new associated adverse effects that the ophthalmologist must recognize and manage.

[HDL-cholesterol concentration and risk of SARS-CoV-2 infection in people over 75 years of age: a cohort with half a million participants from the Community of Madrid].

Objective: The aim of this study was to analyze the relationship between HDL-cholesterol and the risk of SARS-CoV-2 infection in over 75-year-olds residing in the Community of Madrid.

Methods: Study of a population-based cohort, composed of all residents in Madrid (Spain) born before January 1, 1945 and alive on December 31, 2019. Demographic, clinical and analytical data were obtained from primary care electronic medical records from January 2015.

Dysregulated Cell Homeostasis and miRNAs in Human iPSC-Derived Cardiomyocytes from a Propionic Acidemia Patient with Cardiomyopathy.

Propionic acidemia (PA) disorder shows major involvement of the heart, among other alterations. A significant number of PA patients develop cardiac complications, and available evidence suggests that this cardiac dysfunction is driven mainly by the accumulation of toxic metabolites. To contribute to the elucidation of the mechanistic basis underlying this dysfunction, we have successfully generated cardiomyocytes through the differentiation of induced pluripotent stem cells (iPSCs) from a PCCB patient and its isogenic control.

Baricitinib or imatinib in hospitalized COVID-19 patients: Results from COVINIB, an exploratory randomized clinical trial.

Baricitinib and imatinib are considered therapies for coronavirus disease 2019 (COVID-19), but their ultimate clinical impact remains to be elucidated, so our objective is to determine whether these kinase inhibitors provide benefit when added to standard care in hospitalized COVID-19 patients. Phase-2, open-label, randomized trial with a pick-the-winner design conducted from September 2020 to June 2021 in a single Spanish center. Hospitalized adults with COVID-19 pneumonia and a symptom duration ≤10 days were assigned to 3 arms: imatinib (400 mg qd, 7 days) plus standard-care, baricitinib (4 mg qd, 7 days) plus standard-care, or standard-care alone.