Usefulness of Intraoperative Neurophysiological Monitoring in Intradural Spinal Tumor Surgeries.

Due to the absence of studies supporting the role of intraoperative neurophysiological monitoring (IONM) in intradural spinal tumors, this study evaluates the clinical outcome after these surgeries in relation to the use of the advanced intraoperative neurophysiological techniques. This is an observational, descriptive and retrospective study of two cohort groups in relation to the presence or absence of IONM during the intervention and the subsequent evaluation of the clinical and functional results in the short and medium terms. Ninety-six patients with extra- or intramedullary intradural spinal tumors operated on by the neurosurgery team of our center completed the current study.

Funding multinational investigator-initiated clinical studies in Europe: why and how?

Investigator-initiated clinical studies (IICSs), also referred to as non-commercial, academic or independent clinical studies, address important research questions that are usually neglected by industry despite their high societal value. Indeed, industry may direct their focus and resources on studies that will yield results and products that can ultimately generate revenue for the company. Conversely, IICS research questions include (a) refining or getting new indications of available treatments (drug repurposing); (b) optimisation, by comparing various health products or treatment regimens; and (c) innovation, especially for advanced therapies.

Social Cognition in Parkinson's Disease after Focused Ultrasound Subthalamotomy: A Controlled Study.

Social cognition (SC) encompasses a set of cognitive functions that enable individuals to understand and respond appropriately to social interactions. Although focused ultrasound subthalamotomy (FUS-STN) effectively treats Parkinson's disease (PD) clinical motor features, its impact and safety on cognitive-behavioral interactions/interpersonal awareness are unknown. This study investigated the effects of unilateral FUS-STN on facial emotion recognition (FER) and affective and cognitive theory of mind (ToM) in PD patients from a randomized sham-controlled trial (NCT03454425).

Minimal quantum heat pump based on high-frequency driving and non-Markovianity.

We propose a minimal setup for a quantum heat pump consisting of two tunnel-coupled quantum dots, each hosting a single level and each being coupled to a different fermionic reservoir. The working principle relies on both non-Markovian system-bath coupling and driving-induced resonant coupling. We describe the system using a reaction-coordinate mapping in combination with Floquet-Born-Markov theory and characterize its performance.

Nigrostriatal blood-brain barrier opening in Parkinson's disease.

Background: The nigrostriatal system is especially vulnerable to neurodegeneration in Parkinson's disease (PD) and the blood-brain barrier (BBB) is a limiting factor for delivery of therapeutic agents to the brain. This pilot study aimed to demonstrate safety, feasibility and tissue penetration (by 18F-Choline-positron emission tomography (PET)) of MR-guided focused ultrasound (MRgFUS) simultaneous BBB opening (BBB-O) in the substantia nigra (SN) and putamen in PD.

Methods: Three patients underwent MRgFUS for midbrain and putamen BBB-O.

Skull Density Ratio as Arm-Allocation Parameter for a Controlled Focused Ultrasound Trial in Parkinson's Disease.

Background: MR-guided focused ultrasound (FUS) thermoablation is an established therapy for movement disorders. FUS candidates must meet a predefined threshold of skull density ratio (SDR), a parameter that accounts for the efficiency in reaching ablative temperatures. Randomized sham-controlled trials to provide definitive therapeutic evidence employ pure randomization of subjects into active treatment or control arms.

Staged Bilateral MRI-Guided Focused Ultrasound Subthalamotomy for Parkinson Disease.

Importance: Unilateral magnetic resonance imaging (MRI)-guided focused ultrasound subthalamotomy (FUS-STN) improves cardinal motor features among patients with asymmetrical Parkinson disease (PD). The feasibility of bilateral FUS-STN is as yet unexplored.

Objective: To assess the safety and effectiveness of staged bilateral FUS-STN to treat PD.

The Sleeve Gastrectomy with Jejunal Bypass (Original Technique).

Sleeve gastrectomy with jejunal bypass (SGJB) has been used as a bariatric/metabolic procedure since 2003, in the search for a simpler than other standard techniques and as effective as them. The jejunal-ileal anastomosis can deliver food directly to the hindgut where incretins are secreted. This procedure has gained popularity around the globe and has been studied in rat models as in humans, especially in South America and Asia.

Unilateral focused ultrasound subthalamotomy in early Parkinson's disease: a pilot study.

Background: Unilateral focused ultrasound subthalamotomy (FUS-STN) improves motor features of Parkinson's disease (PD) in moderately advanced patients. The less invasive nature of FUS makes its early application in PD feasible. We aim to assess the safety and efficacy of unilateral FUS-STN in patients with PD of less than 5 years from diagnosis (early PD).

Canine Mammary Neoplasia Induces Variations in the Peripheral Blood Levels of CD20, CD45RA, and CD99.

The idea of using tumour biomarkers as diagnostic tools is progressively increasing. Of these, serum biomarkers are of particular interest, as they can provide rapid results. In the present study, serum samples from 26 bitches diagnosed with mammary tumours, plus 4 healthy bitches, were obtained.

BBB opening with focused ultrasound in nonhuman primates and Parkinson's disease patients: Targeted AAV vector delivery and PET imaging.

Intracerebral vector delivery in nonhuman primates has been a major challenge. We report successful blood-brain barrier opening and focal delivery of adeno-associated virus serotype 9 vectors into brain regions involved in Parkinson's disease using low-intensity focus ultrasound in adult macaque monkeys. Openings were well tolerated with generally no associated abnormal magnetic resonance imaging signals.

Trial of Globus Pallidus Focused Ultrasound Ablation in Parkinson's Disease.

Background: Unilateral focused ultrasound ablation of the internal segment of globus pallidus has reduced motor symptoms of Parkinson's disease in open-label studies.

Methods: We randomly assigned, in a 3:1 ratio, patients with Parkinson's disease and dyskinesias or motor fluctuations and motor impairment in the off-medication state to undergo either focused ultrasound ablation opposite the most symptomatic side of the body or a sham procedure. The primary outcome was a response at 3 months, defined as a decrease of at least 3 points from baseline either in the score on the Movement Disorders Society-Unified Parkinson's Disease Rating Scale, part III (MDS-UPDRS III), for the treated side in the off-medication state or in the score on the Unified Dyskinesia Rating Scale (UDysRS) in the on-medication state.

Efficacy and safety of baricitinib in hospitalized adults with severe or critical COVID-19 (Bari-SolidAct): a randomised, double-blind, placebo-controlled phase 3 trial.

Background: Baricitinib has shown efficacy in hospitalized patients with COVID-19, but no placebo-controlled trials have focused specifically on severe/critical COVID, including vaccinated participants.

Methods: Bari-SolidAct is a phase-3, multicentre, randomised, double-blind, placebo-controlled trial, enrolling participants from June 3, 2021 to March 7, 2022, stopped prematurely for external evidence. Patients with severe/critical COVID-19 were randomised to Baricitinib 4 mg once daily or placebo, added to standard of care.

Identifying obstacles hindering the conduct of academic-sponsored trials for drug repurposing on rare-diseases: an analysis of six use cases.

Background: Academic-sponsored trials for rare diseases face many challenges; the present paper identifies hurdles in the set-up of six multinational clinical trials for drug repurposing, as use cases.

Methods: Six academic-sponsored multinational trials aiming to generate knowledge on rare diseases drug repurposing were used as examples to identify problems in their set-up. Coordinating investigators leading these trials provided feedback on hurdles linked to study, country, and site set up, on the basis of pre-identified categories established through the analysis of previous peer-reviewed publications.

Effects of deep brain stimulation on the kinematics of gait and balance in patients with idiopathic Parkinson's disease.

Background: Advanced stages of idiopathic Parkinson's disease are often characterised by gait alterations and postural instability. Despite improvements in patients' motor symptoms after deep brain stimulation of the subthalamic nucleus, its effects on gait and balance remain a matter of debate. This study investigated the effects of deep brain stimulation on balance and kinematic parameters of gait.

Tenofovir Disoproxil Fumarate/Emtricitabine and Baricitinib for Patients at High Risk of Severe Coronavirus Disease 2019: The PANCOVID Randomized Clinical Trial.

Background: This study was designed to evaluate if patients with high risk for severe coronavirus disease 2019 (COVID-19) would benefit from treatment with tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) followed by baricitinib in case of hypoxemia and systemic inflammation.

Methods: PANCOVID is an open-label, double-randomized, phase 3 pragmatic clinical trial including adults with symptomatic COVID-19 with ≥2 comorbidities or aged ≥60 years and was conducted between 10 October 2020 and 23 September 2021. In the first randomization, patients received TDF/FTC or no TDF/FTC.

Striatal Blood-Brain Barrier Opening in Parkinson's Disease Dementia: A Pilot Exploratory Study.

Background: Parkinson's disease (PD) exhibits a high prevalence of dementia as disease severity and duration progress. Focused ultrasound (FUS) has been applied for transient blood-brain barrier (BBB) opening of cortical regions in neurodegenerative disorders. The striatum is a primary target for delivery of putative therapeutic agents in PD.

Hepatitis E virus genotype 3 microbiological surveillance by the Spanish Reference Laboratory: geographic distribution and phylogenetic analysis of subtypes from 2009 to 2019.

BackgroundHepatitis E virus genotype 3 (HEV-3) is widely distributed throughout Europe, with incidence of infections increasing in many countries. Belgium, Bulgaria, France, Germany, Italy, the Netherlands and the United Kingdom have reported the distribution of HEV-3 subtypes in cohorts of patients with hepatic disease.AimTo describe the distribution of the HEV-3 subtypes in Spain at national and autonomous community (AC) levels between 2009 and 2019.

Neuroimaging signatures predicting motor improvement to focused ultrasound subthalamotomy in Parkinson's disease.

Subthalamotomy using transcranial magnetic resonance-guided focused ultrasound (tcMRgFUS) is a novel and promising treatment for Parkinson's Disease (PD). In this study, we investigate if baseline brain imaging features can be early predictors of tcMRgFUS-subthalamotomy efficacy, as well as which are the post-treatment brain changes associated with the clinical outcomes. Towards this aim, functional and structural neuroimaging and extensive clinical data from thirty-five PD patients enrolled in a double-blind tcMRgFUS-subthalamotomy clinical trial were analyzed.

Combined Stimulation of the Substantia Nigra and the Subthalamic Nucleus for the Treatment of Refractory Gait Disturbances in Parkinson's Disease: A Preliminary Study.

Deep brain stimulation of the subthalamic nucleus is efficient for the treatment of motor symptoms (i.e., tremors) in patients with Parkinson's disease.

Durable Response to Vemurafenib and Cobimetinib for the Treatment of BRAF-Mutated Metastatic Melanoma in Routine Clinical Practice.

Background: The combination of and inhibitors delays the onset of resistance and provides more sustained and dramatic responses in comparison with a inhibitor in monotherapy. The objective of the study was to evaluate the effectiveness of the combination therapy with vemurafenib/cobimetinib in terms of durability, and to describe differential characteristics in patients associated to durable responses in real-world settings.

Patients And Methods: Retrospective, observational, cross-sectional, multicenter study involving 41 patients with advanced melanoma harboring a mutation who initiated a combination therapy with vemurafenib/cobimetinib between May 2018 and March 2019.

Functional Topography of the Human Subthalamic Nucleus: Relevance for Subthalamotomy in Parkinson's Disease.

Background: The subthalamic nucleus (STN) is considered a key structure in motor, behavioral, and emotional control. Although identification of the functional topography of the STN has therapeutic implications in the treatment of the motor features of Parkinson's disease (PD), the details of its functional and somatotopic organization in humans are not well understood.

Objective: The aim of this study was to characterize the functional organization of the STN and its correlation with the motor outcomes induced by subthalamotomy.