Canonical Wnt pathway and the LDL receptor superfamily in neuronal cholesterol homeostasis and function.

Aims: There is little information on the regulation of cholesterol homeostasis in the brain. Whether cholesterol crosses the blood-brain barrier is under investigation, but the present understanding is that cholesterol metabolism in the brain is independent from that in peripheral tissues. Lipoprotein receptors from the LDL receptor family (LRPs) have key roles in lipid particle accumulation in cells involved in vascular and cardiac pathophysiology; however, their function on neural cells is unknown.

Phase II trial of CDK4/6 inhibitor palbociclib in advanced sarcoma based on mRNA expression of CDK4/ CDKN2A.

Cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors demonstrated activity in terms of progression-free survival (PFS) in advanced dedifferentiated liposarcoma (DD-LPS), a sarcoma with CDK4 amplification. CDK4 overexpression is by far more common than amplification in sarcomas and it might be a rational target for CDK inhibitors. Preclinical investigators of this study found that CDK4 overexpression, while not of CDKN2A, was the most consistent predictive factor for palbociclib efficacy in sarcomas.

The Hybrid Closed-Loop System Tandem t:slim X2™ with Control-IQ Technology: Expert Recommendations for Better Management and Optimization.

Technological advances in the management of diabetes, especially type 1 diabetes (T1D), have played a main role in significantly improving glycemic control of these patients in recent years. Undoubtedly, the most important advance has been the commercialization of hybrid closed-loop systems (HCL). Their effectiveness places them in the different guidelines from scientific societies as the gold standard for the treatment of people with T1D.

Myocarditis with concomitant tuberculosis infection presenting with solitary ventricular tachycardia: a case report.

Background: Myocarditis is an infrequent extrapulmonary manifestation of tuberculosis that confers an unfavourable prognosis.

Case Summary: A 36-year-old man presented to the hospital with palpitations and dyspnoea. Tests revealed the presence of non-sustained ventricular tachycardia, with mild elevation of troponin and C-reactive protein levels.

Current Approach in the Management of Secondary Immunodeficiency in Patients with Hematological Malignancies: Spanish Expert Consensus Recommendations.

A Delphi-based survey was designed to assess the opinions of clinical hematologists (n = 17) and clinical immunologists (n = 18) from across Spain on secondary immunodeficiencies (SID) in the management of oncohematological patients. There was 100% agreement on the need to have available guidelines for the management of immunodeficiency in hematological patients; to perform a baseline immunological evaluation in patients with chronic lymphocytic leukemia (CLL), multiple myeloma (MM), lymphoma and hematopoietic stem cell transplantation (HSCT) recipients; and to quantify serum IgG, IgA and IgM levels when SID is suspected. More than 90% agreed on the need for active immunization against seasonal influenza and H1N1, pneumococcus and .

Quality control to improve LDL-cholesterol management in patients with acute coronary syndromes based on the ACS EuroPath IV project.

Aims: We performed quality control of lipid-lowering therapy (LLT) in patients with acute coronary syndrome (ACS), with a view to proposing corrective actions.

Methods And Results: Using a Define Measure Analysis Improve Control (DMAIC) approach applied to data from the ACS EuroPath IV survey, we measured attainment of two quality indicators (QIs) related to lipid-lowering treatment: (i) prescription of high-intensity statins (or equipotent treatment) before discharge, and (ii) proportion with LDL-cholesterol <55 mg/dL (1.4 mmol/L) during follow-up.

Are all JAK inhibitors for the treatment of rheumatoid arthritis equivalent? An adjusted indirect comparison of the efficacy of tofacitinib, baricitinib, upadacitinib, and filgotinib.

Introduction: Comparisons of Janus kinase inhibitors (JAKi) for treatment of rheumatoid arthritis in patients with inadequate response to biologic disease-modifying anti-rheumatic drugs are lacking. We assessed the relative efficacy and safety of four JAKi (tofacitinib, baricitinib, upadacitinib, and filgotinib) in this context.

Method: We performed an adjusted indirect comparison (IC) of randomized clinical trials using Bucher's method with an IC and mixed calculator.

Three-Photon Infrared Stimulation of Endogenous Neuroreceptors in Vivo.

To interrogate neural circuits and crack their codes, in vivo brain activity imaging must be combined with spatiotemporally precise stimulation in three dimensions using genetic or pharmacological specificity. This challenge requires deep penetration and focusing as provided by infrared light and multiphoton excitation, and has promoted two-photon photopharmacology and optogenetics. However, three-photon brain stimulation in vivo remains to be demonstrated.

Blood DNA methylation signature of diet quality and association with cardiometabolic traits.

Aims: Diet quality might influence cardiometabolic health through epigenetic changes, but this has been little investigated in adults. Our aims were to identify cytosine-phosphate-guanine (CpG) dinucleotides associated with diet quality by conducting an epigenome-wide association study (EWAS) based on blood DNA methylation (DNAm) and to assess how diet-related CpGs associate with inherited susceptibility to cardiometabolic traits: body mass index (BMI), systolic blood pressure (SBP), triglycerides, type 2 diabetes (T2D), and coronary heart disease (CHD).

Methods And Results: Meta-EWAS including 5274 participants in four cohorts from Spain, the USA, and the UK.

Frailty and mortality: Utility of Frail-VIG index in ED short-stay units for older adults.

Background: Frailty assessment allows the identification of patients at risk of death. The aim here was to study the ability of Frail-VIG Index (FI-VIG) in order to discriminate frailty groups of older adults and garner its correlation with mortality in an Emergency-Department Short-Stay Unit (ED-SSU).

Methods: Our observational, single-center, prospective study consecutively included patients over 65-years-old admitted between March 1, 2021, and April 30, 2021.

Impact of Baseline Anemia in Patients Undergoing Transcatheter Aortic Valve Replacement: A Prognostic Systematic Review and Meta-Analysis.

Transcatheter aortic valve replacement (TAVR) is currently the treatment of choice for patients aged ≥75 years with severe aortic stenosis. Preoperative anemia is present in a large proportion of patients and may increase the risk of post-procedural complications. The purpose of this prognostic systematic review was to analyze the impact of baseline anemia on short- and mid-term outcomes following TAVR.

An Analysis of JADE2 in Non-Small Cell Lung Cancer (NSCLC).

The JADE family comprises three members encoded by individual genes and roles for these proteins have been identified in chromatin remodeling, cell cycle progression, cell regeneration and the DNA damage response. JADE family members, and in particular JADE2 have not been studied in any great detail in cancer. Using a series of standard biological and bioinformatics approaches we investigated JADE2 expression in surgically resected non-small cell lung cancer (NSCLC) for both mRNA and protein to examine for correlations between JADE2 expression and overall survival.

SYNAPSES. A European observational study to evaluate the safety and the effectiveness of safinamide in routine clinical practice: post-hoc analysis of the Spanish study population.

Introduction: Parkinson's Disease (PD) is a progressive age-related neurodegenerative condition requiring new therapeutic alternatives. Safinamide, a novel levodopa add-on therapy, positively affects disease fluctuations by modulating both dopaminergic and glutamatergic systems. To further investigate the use of safinamide in European routine clinical practice, the present post-hoc analysis aimed to understand safinamide's safety profile within the Spanish study population.

Clinical characteristics and outcome of amaurosis fugax due to transient retinal ischemia: Results from a contemporary cohort.

Background: Whether presenting an episode of amaurosis fugax (AFx) increases the risk of ischemic stroke is controversial and there is a lack of consensus in the following management. We aimed to describe the clinical characteristics and prognosis of patients with AFx due to suspected transient retinal ischemia.

Methods: Observational, retrospective study of patients admitted in a Comprehensive Stroke Center with diagnosis of AFx due to suspected transient retinal ischemia between 2015 and 2020.

Sequential management of postmenopausal health and osteoporosis: An update.

Increased life expectancy means that women are now in a hypoestrogenic state for approximately one-third of their lives. Overall health and specifically bone health during this period evolves in accordance with aging and successive exposure to various risk factors. In this review, we provide a summary of the approaches to the sequential management of osteoporosis within an integrative model of care to offer physicians a useful tool to facilitate therapeutic decision-making.

Clinico-Pathological Features, Outcomes and Impacts of COVID-19 Pandemic on Patients with Early-Onset Colorectal Cancer: A Single-Institution Experience.

Background: The rising incidence of colorectal cancer (CRC) among young patients is alarming. We aim to characterize the clinico-pathological features and outcomes of patients with early-onset CRC (EOCRC), as well as the impacts of COVID-19 pandemic.

Methods: We included all patients with pathologically confirmed diagnoses of CRC at Hospital Universitario La Paz from October 2016 to December 2021.

High-precision targeting and destruction of cancer-associated PDGFR-β stromal fibroblasts through self-assembling, protein-only nanoparticles.

The need for more effective and precision medicines for cancer has pushed the exploration of new materials appropriate for drug delivery and imaging, and alternative receptors for targeting. Among the most promising strategies, finding suitable cell surface receptors and targeting agents for cancer-associated platelet derived growth factor receptor β (PDGFR-β) stromal fibroblasts is highly appealing. As a neglected target, this cell type mechanically and biologically supports the growth, progression, and infiltration of solid tumors in non-small cell lung, breast, pancreatic, and colorectal cancers.

The Relevance of Implementing the Systematic Screening of Perioperative Myocardial Injury in Noncardiac Surgery Patients.

Perioperative myocardial injury (PMI) is a common cardiac complication. Recent guidelines recommend its systematic screening using high-sensitivity cardiac troponin (hs-cTn). However, there is limited evidence of local screening programs.

Validation Study of the PALCOM Scale of Complexity of Palliative Care Needs: A Cohort Study in Advanced Cancer Patients.

Background: In a patient-centred model of care, referral to early palliative care (EPC) depends on both the prognosis and the complexity of care needs. The PALCOM scale is a 5-domain multidimensional assessment tool developed to identify the level of complexity of palliative care needs of cancer patients. The aim of this study was to validate the PALCOM scale.