Prevention of excitotoxicity-induced processing of BDNF receptor TrkB-FL leads to stroke neuroprotection.

Neuroprotective strategies aimed to pharmacologically treat stroke, a prominent cause of death, disability, and dementia, have remained elusive. A promising approach is restriction of excitotoxic neuronal death in the infarct penumbra through enhancement of survival pathways initiated by brain-derived neurotrophic factor (BDNF). However, boosting of neurotrophic signaling after ischemia is challenged by downregulation of BDNF high-affinity receptor, full-length tropomyosin-related kinase B (TrkB-FL), due to calpain-degradation, and, secondarily, regulated intramembrane proteolysis.

Management of anticoagulation in patients undergoing leadless pacemaker implantation.

Background: The Micra transcatheter pacing system (Micra TPS) is often implanted in patients with atrial fibrillation and thus with increased thromboembolic risk. It is unknown whether the use of anticoagulants, associated with the use of a large venous introducer, implies an increased risk of bleeding in this group of patients.

Objective: The purpose of this study was to assess the incidence of bleeding and thromboembolic complications after Micra TPS implantation with and without therapeutic anticoagulation.

Healthcare resource utilization and associated cost analysis of the PROCLAIM study in patients with stage III non-small-cell lung cancer.

To analyze patient-reported swallowing difficulties, healthcare resource utilization and associated costs during the PROCLAIM study. Patients with stage III non-squamous non-small cell lung cancer received pemetrexed-cisplatin (PemCis) combined with concurrent thoracic radiotherapy followed by consolidation pemetrexed, or concurrent chemoradiotherapy with etoposide-cisplatin (EtoCis) followed by standard consolidation chemotherapy. Patient - reported swallowing function was measured using diaries.

Electrocardiographic optimization techniques in resynchronization therapy.

Cardiac resynchronization therapy (CRT) is a cornerstone of therapy for patients with heart failure, reduced left ventricular (LV) ejection fraction, and a wide QRS complex. However, not all patients respond to CRT: 30% of CRT implanted patients are currently considered clinical non-responders and up to 40% do not achieve LV reverse remodelling. In order to achieve the best CRT response, appropriate patient selection, device implantation, and programming are important factors.

Empagliflozin Ameliorates Adverse Left Ventricular Remodeling in Nondiabetic Heart Failure by Enhancing Myocardial Energetics.

Background: Empagliflozin cardiac benefits in the EMPA-REG OUTCOME (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients) trial cannot be explained exclusively by its antihyperglycemic activity.

Objectives: The hypothesis was that empagliflozin's cardiac benefits are mediated by switching myocardial fuel metabolism away from glucose toward ketone bodies (KB), which improves myocardial energy production.

Methods: Heart failure was induced in nondiabetic pigs (n = 14) by 2-h balloon occlusion of the proximal left anterior descending artery.

Failure-free survival of the Riata implantable cardioverter-defibrillator lead after a very long-term follow-up.

Aims: Riata implantable cardioverter-defibrillator (ICD) leads from St. Jude Medical are prone to malfunction. This study aimed to describe the rate of this lead's malfunction in a very long-term follow-up.

Ocean acidification alters morphology of all otolith types in Clark's anemonefish ().

Ocean acidification, the ongoing decline of surface ocean pH and [CO ] due to absorption of surplus atmospheric CO, has far-reaching consequences for marine biota, especially calcifiers. Among these are teleost fishes, which internally calcify otoliths, critical elements of the inner ear and vestibular system. There is evidence in the literature that ocean acidification increases otolith size and alters shape, perhaps impacting otic mechanics and thus sensory perception.

Ascertaining the epidemiology, patient flow and disease management for Dravet syndrome in Spain.

Introduction: Dravet syndrome (DS) is a rare, drug resistant epilepsy that starts very early in life with febrile seizures followed by cognitive impairment and diverse seizure types.

Aim: To generate evidence on the epidemiology of DS, its diagnosis, patient-flow, treatment and unmet needs from the perspective of Spanish experts.

Development: A two-round Delphi study involving 19 physicians was conducted.

Effect of pulmonary artery denervation in postcapillary pulmonary hypertension: results of a randomized controlled translational study.

There is scarce evidence for pulmonary artery denervation (PADN) as a potential treatment for chronic postcapillary pulmonary hypertension (PH). We aimed to perform a proof-of-concept of PADN in a translational model of chronic PH. Nineteen pigs with chronic postcapillary PH (secondary to pulmonary vein banding) were randomized to surgical-PADN (using bipolar radiofrequency clamps) or sham procedure.

Determining the best approach to reduce the impact of exercise-induced atrial fibrillation: prevention, screening, or symptom-based treatment?

: Regular endurance exercise over the course of many years appears to increase the risk of atrial fibrillation (AF). These data challenge the notion that the benefits of physical activity have no appreciable limits. The incidence of exercise-induced AF is expected to increase as a consequence of the popularity of extreme endurance sports.

Radiation Therapy Quality Assurance (RTQA) of Concurrent Chemoradiation Therapy for Locally Advanced Non-Small Cell Lung Cancer in the PROCLAIM Phase 3 Trial.

Purpose: Chemoradiation therapy trials of different tumors, including lung cancer, have shown a correlation between protocol deviations and adverse outcomes. Radiation therapy quality assurance (RTQA) was mandated for all patients treated in the PROCLAIM trial evaluating 2 different chemoradiation therapy regimens. The RTQA results were evaluated from the PROCLAIM study, and the impact of irradiation deviations on efficacy outcomes was investigated.

The Impact of Staging by Positron-Emission Tomography on Overall Survival and Progression-Free Survival in Patients With Locally Advanced NSCLC.

Introduction: We investigated the potential impact of stage migration because of positron-emission tomography (PET) scan staging on survival in the locally advanced (stage IIIA/B) NSCLC setting.

Methods: In PROCLAIM, 598 patients with stage IIIA/B nonsquamous NSCLC (intent-to-treat population) were randomized to either pemetrexed plus cisplatin and concurrent thoracic radiotherapy for 3 cycles followed by 4 cycles of pemetrexed consolidation or etoposide plus cisplatin and concurrent thoracic radiotherapy for 2 cycles followed by a consolidation platinum-based doublet regimen for up to 2 cycles. Baseline PET scan (PET Yes versus No) was one of the stratification factors.

Evaluation of changes in renal function in PARAMOUNT: a phase III study of maintenance pemetrexed plus best supportive care versus placebo plus best supportive care after induction treatment with pemetrexed plus cisplatin for advanced nonsquamous non-small-cell lung cancer.

Objectives: To assess the effect of long-term pemetrexed maintenance therapy on patients' renal function.

Methods: In the PARAMOUNT phase III trial (NCT 00789373), pemetrexed was compared with placebo as maintenance treatment in advanced nonsquamous non-small-cell lung cancer patients who completed 4 cycles of pemetrexed plus cisplatin induction therapy. To evaluate changes in renal function during pemetrexed continuation maintenance treatment, we retrospectively analyzed changes in serum creatinine (sCr), treatment-emergent adverse events, dose delays and treatment discontinuations associated with impaired renal function.

New holosystolic murmur after acute myocardial infarction.

In the era of primary percutaneous coronary intervention, mechanical complications after acute myocardial infarction are extremely rare, with an incidence of less than 0.5%. Rupture of the ventricular septum is the least frequent occurrence.

Serum levels of Growth Arrest-Specific 6 protein and soluble AXL in patients with ST-segment elevation myocardial infarction.

Background: Serum soluble AXL (sAXL) and its ligand, Growth Arrest-Specific 6 protein (GAS6), intervene in tissue repair processes. AXL is increased in end-stage heart failure, but the role of GAS6 and sAXL in ST-segment elevation myocardial infarction (STEMI) is unknown.

Objectives: To study the association of sAXL and GAS6 acutely and six months following STEMI with heart failure and left ventricular remodelling.

The collαgen III fibril has a "flexi-rod" structure of flexible sequences interspersed with rigid bioactive domains including two with hemostatic roles.

Collagen III is critical to the integrity of blood vessels and distensible organs, and in hemostasis. Examination of the human collagen III interactome reveals a nearly identical structural arrangement and charge distribution pattern as for collagen I, with cell interaction domains, fibrillogenesis and enzyme cleavage domains, several major ligand-binding regions, and intermolecular crosslink sites at the same sites. These similarities allow heterotypic fibril formation with, and substitution by, collagen I in embryonic development and wound healing.

A rare cause of severe mitral stenosis and reversible pulmonary hypertension.

Myxoma is a rare cause of severe mitral stenosis. We describe a challenging case of severe mitral stenosis and reversible pulmonary hypertension produced by a giant left atrial myxoma. The greatest risk is a diagnostic delay due to focus on discarding a pulmonary etiology of dyspnea.

Safety Analyses of Pemetrexed-cisplatin and Pemetrexed Maintenance Therapies in Patients With Advanced Non-squamous NSCLC: Retrospective Analyses From 2 Phase III Studies.

Background: In a phase III study, maintenance pemetrexed showed superior survival over placebo (PARAMOUNT) for patients with advanced non-squamous non-small cell lung cancer (NSCLC) who completed 4 cycles of pemetrexed plus cisplatin (PC) induction therapy, with low incidence of treatment-emergent adverse events (TEAEs) generally associated with pemetrexed. Prior analyses did not account for toxicities carried over from induction; thus, the current analysis was developed to understand toxicities that may be attributed to pemetrexed maintenance versus PC induction, and how treatment duration affects toxicity.

Patients And Methods: Selected clinically relevant TEAEs were explored in 2 analyses: assessing induction versus maintenance treatment in PARAMOUNT, and comparing PC from PARAMOUNT with toxicity data from a previous phase III study that established the role of PC in front-line therapy of non-squamous NSCLC (JMDB trial).