Value contribution of etranacogene dezaparvovec gene therapy in moderately severe and severe haemophilia B through multi-criteria decision analysis.

Introduction: The value of gene therapies for haemophilia needs to be assessed holistically.

Aim: To determine the value of etranacogene dezaparvovec (ED) compared to current extended half-life (EHL) recombinant factors (rFIX), using multi-criteria decision analysis (MCDA).

Method: MCDA EVIDEM methodology adapted to orphan drugs was used, with nine quantitative criteria and four contextual criteria.

European society of clinical microbiology and infectious diseases guidelines for antimicrobial stewardship in emergency departments (endorsed by European association of hospital pharmacists).

Scope: This European Society of Clinical Microbiology and Infectious Diseases guideline provides evidence-based recommendations to support a selection of appropriate antibiotic use practices for patients seen in the emergency department (ED) and guidance for their implementation. The topics addressed in this guideline are (a) Do biomarkers or rapid pathogen tests improve antibiotic prescribing and/or clinical outcomes? (b) Does taking blood cultures in common infectious syndromes improve antibiotic prescribing and/or clinical outcomes? (c) Does watchful waiting without antibacterial therapy or with delayed antibiotic prescribing reduce antibiotic prescribing without worsening clinical outcomes in patients with specific infectious syndromes? (d) Do structured culture follow-up programs in patients discharged from the ED with cultures pending improve antibiotic prescribing?

Methods: An expert panel was convened by European Society of Clinical Microbiology and Infectious Diseases and the guideline chair. The panel selected in consensus the four most relevant antimicrobial stewardship topics according to pre-defined relevance criteria.

Epidemiology and Risk Factors of Mycotic Aneurysm in Patients With Infective Endocarditis and the Impact of its Rupture in Outcomes. Analysis of a National Prospective Cohort.

Background: Several aspects of the occurrence and management of mycotic aneurysm (MA) in patients with infective endocarditis (IE) have not been studied.

Objectives: To determine the incidence and factors associated with MA presence and rupture and to assess the evolution of those initially unruptured MA.

Methods: Prospective multicenter cohort including all patients with definite IE between January 2008 and December 2020.

Different outcomes among patients with intermediate-risk metastastic renal cell carcinoma treated with first-line tyrosine-kinase inhibitors.

Introduction: Systemic therapy of patients with metastatic renal cell carcinoma (mRCC) has improved in the past years, with the advent of new immunotherapy-based combinations as a standard treatment option for first-line therapy. Nevertheless, particularly in good-risk patients by IMDC criteria, tyrosine-kinase inhibitors (TKI) may remain as an option for some patients. We reviewed our experience with TKI as first-line therapy for mRCC patients, trying to identify subgroups of patients that may still benefit from this strategy.

Social Media Use Among Members of the Assessment of Spondyloarthritis International Society: Results of a Web-Based Survey.

Background: The use of social media in health care may serve as a beneficial tool for education, information dissemination, telemedicine, research, networking, and communications. To better leverage the benefits of social media, it is imperative to understand the patterns of its use and potential barriers to its implementation in health care. A previous study in 2016 that investigated social media use among young clinical rheumatologists (≤45 years) and basic scientists showed that there was substantial social media use among them for social and professional reasons.

Rapid, scalable assessment of SARS-CoV-2 cellular immunity by whole-blood PCR.

Fast, high-throughput methods for measuring the level and duration of protective immune responses to SARS-CoV-2 are needed to anticipate the risk of breakthrough infections. Here we report the development of two quantitative PCR assays for SARS-CoV-2-specific T cell activation. The assays are rapid, internally normalized and probe-based: qTACT requires RNA extraction and dqTACT avoids sample preparation steps.

Supplementation with the Symbiotic Formulation Prodefen Increases Neuronal Nitric Oxide Synthase and Decreases Oxidative Stress in Superior Mesenteric Artery from Spontaneously Hypertensive Rats.

In recent years, gut dysbiosis has been related to some peripheral vascular alterations linked to hypertension. In this work, we explore whether gut dysbiosis is related to vascular innervation dysfunction and altered nitric oxide (NO) production in the superior mesenteric artery, one of the main vascular beds involved in peripheral vascular resistance. For this purpose, we used spontaneously hypertensive rats, either treated or not with the commercial synbiotic formulation Prodefen (10 colony forming units/day, 4 weeks).

The human-specific duplicated α7 gene inhibits the ancestral α7, negatively regulating nicotinic acetylcholine receptor-mediated transmitter release.

Gene duplication generates new functions and traits, enabling evolution. Human-specific duplicated genes in particular are primary sources of innovation during our evolution although they have very few known functions. Here we examine the brain function of one of these genes (CHRFAM7A) and its product (dupα7 subunit).

A Blunted Sympathetic Function and an Enhanced Nitrergic Activity Contribute to Reduce Mesenteric Resistance in Hyperthyroidism.

We aimed to determine whether an experimental model of hyperthyroidism could alter the function of sympathetic and nitrergic components of mesenteric innervation. For this purpose, male Wistar rats were divided into (1) control rats (CT) and (2) rats infused with L-Thyroxine (HT). Body weight gain and adipose tissue accumulation were lower in HT rats, while systolic blood pressure and citrate synthase activity in the soleus muscle were increased by HT.

Treatment strategy optimization for patients with non-small-cell lung cancer harboring EGFR mutation: a Delphi consensus.

Aim: To stablish a consensus on the treatment strategy for advanced non-small-cell lung cancer (aNSCLC) with epidermal growth factor receptor mutation (EGFRm) in Spain.

Methods: After a systematic literature review, the scientific committee developed 33 statements in 4 fields: molecular diagnosis (10 items); histologic profile and patient clinical characteristics (7 items); first-line (1L) treatment in EGFRm aNSCLC (8 items); and subsequent-line treatment (8 items). A panel of 31 experts completed 2 Delphi online questionnaires rating their degree of agreement/disagreement for each statement through a 1-9 range scale (1-3 = disagree, 7-9 = agree).

Enhanced sympathetic neurotransduction in the superior mesenteric artery in a rat model of heart failure: role of noradrenaline and ATP.

Heart failure (HF) is associated with neurohumoral activation, which in turn leads to an increased peripheral resistance. In mesenteric vasculature, perivascular innervation plays relevant role maintaining vascular tonus and resistance. Therefore, we aimed to determine the possible alterations in superior mesenteric artery (SMA) perivascular innervation function in HF rats.

Insights into the Procoagulant Profile of Patients with Systemic Lupus Erythematosus without Antiphospholipid Antibodies.

We aimed to identify the key players in the prothrombotic profile of patients with systemic lupus erythematosus (SLE) not mediated by antiphospholipid antibodies, as well as the potential utility of global coagulation tests to characterize hemostasis in these patients. Patients with SLE without antiphospholipid antibodies and without signs of thrombosis were included. The kinetics of clot formation were determined by ROTEM.

Behavioural cardiovascular risk factors and prevalence of diabetes in subjects with familial hypercholesterolaemia.

A low prevalence of type 2 diabetes mellitus has been reported in familial hypercholesterolaemia. Whether a healthier lifestyle could explain it has not been explored. This cross-sectional study determines the prevalence of lifestyle-related cardiovascular risk factors in heterozygous familial hypercholesterolaemia (HeFH) from the Dyslipidaemia Registry of the Spanish Atherosclerosis Society and in the ENRICA study, a representative sample of the adult Spanish general population, weighted to match the age and sex distribution of the HeFH sample.

Beneficial Effect of a Multistrain Synbiotic on the Systemic and Vascular Alterations Associated with Metabolic Syndrome in Rats: The Role of the Neuronal Nitric Oxide Synthase and Protein Kinase A.

A high fat diet (HFD) intake is crucial for the development and progression of metabolic syndrome (MtS). Increasing evidence links gut dysbiosis with the metabolic and vascular alterations associated with MtS. Here we studied the use of a combination of various probiotic strains together with a prebiotic (synbiotic) in a commercially available .

Efficacy and safety of abiraterone acetate plus prednisone vs. cabazitaxel as a subsequent treatment after first-line docetaxel in metastatic castration-resistant prostate cancer: results from a prospective observational study (CAPRO).

Background: To describe the patterns of second-line treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) after docetaxel treatment in a Spanish population, to identify the factors associated with those patterns, and to compare the efficacy and safety of the treatments most frequently administered.

Methods: Observational, prospective study conducted in patients with histologically or cytologically confirmed prostate adenocarcinoma; documented metastatic castration-resistant disease; progression after first-line, docetaxel-based chemotherapy with or without other agents.

Results: Of the 150 patients recruited into the study, 100 patients were prescribed abiraterone acetate plus prednisone (AAP), 44 patients received cabazitaxel plus prednisone (CP), and 6 patients received other treatments.

Obstructive sleep apnea is associated with worse clinical-radiological risk scores of pulmonary embolism.

Obstructive sleep apnea is a risk factor for pulmonary embolism, although its association with pulmonary embolism severity is unknown. Our objective was to study if obstructive sleep apnea is associated with worse pulmonary embolism severity scores and greater extent of arterial obstruction. In consecutive pulmonary embolism patients, we performed respiratory polygraphy and recorded sleep characteristics, classical risk factors for pulmonary embolism and physical activity 6-12 months after the pulmonary embolism episode.

Salvage robot-assisted radical prostatectomy following failed local treatments.

Prostate cancer represents the most commonly diagnosed cancer in men and is the second-leading cause of cancer related death in the United States. Primary treatment for prostate cancer includes radiotherapy or ablative procedures such as cryotherapy, and high-intensity focused ultrasound (HIFU). Unfortunately, a large proportion of these patients, especially with high risk features, may experience disease recurrence within 10 years.

Association between sleep characteristics and antihypertensive treatment in older adults.

Aim: The relationship between sleeping characteristics and antihypertensive medication is little known. We examined the association of sleep quality or duration and the use of sleeping pills with the number of antihypertensive drugs used in older adults.

Methods: This was a prospective cohort study of treated hypertensive patients aged ≥60 years participating in a seniors cohort, followed from 2008 to 2010 through 2012 to 2013.

Frailty phenotype: a clinical marker of age acceleration in the older HIV-infected population.

Aim: To evaluate the association between DNA methylation and frailty in the HIV-infected population and to investigate the usefulness of assessing frailty as a clinical marker to identify age acceleration.

Methods: Frailty was assessed according to Fried's frailty phenotype. DNA methylation was analyzed in 10 frail patients, and compared with 10 robust control patients, all with HIV.

Pro-angiogenic near infrared-responsive hydrogels for deliberate transgene expression.

Unlabelled: CuS nanoparticles (CuSNP) are degradable, readily prepared, inexpensive to produce and efficiently cleared from the body. In this work, we explored the feasibility of CuSNP to function as degradable near infrared (NIR) nanotransducers within fibrin-based cellular scaffolds. To prepare NIR-responsive CuSNP hydrogels, fibrinogen was dissolved in cell culture medium and supplemented with aqueous dispersions of CuSNP.

Proximal Femoral Bone Regeneration After an Uncemented Hydroxyapatite-coated Long-stem in Revision Hip Surgery.

Background: Bone remodelling with lateral femoral cortex thinning is a major concern after extensively porous-coated long-stem in revision surgery. Extensive hydroxyapatite coated long-stems were introduced to improve osseointegration, but bone remodelling changes have not been quantified.

Objective: The question of whether bone remodelling changes from extensive hydroxyapatite-coated long stems influence the durability of femoral revision, clinical outcome is assessed in follow-up radiographs.

Association of nicotine metabolism and sex with relapse following varenicline and nicotine replacement therapy.

Nicotine is metabolized into cotinine and then into trans-3'-hydroxycotinine, mainly by cytochrome P450 2A6. Recent studies reported better effectiveness of varenicline in women and in nicotine normal metabolizers phenotypically determined by nicotine-metabolite ratio. Our objective was to study the influence of nicotine-metabolite ratio, CYP2A6 genotype and sex on the response to nicotine replacement therapy and varenicline.