Nine-year prospective efficacy and safety of brain-responsive neurostimulation for focal epilepsy.

Objective: To prospectively evaluate safety and efficacy of brain-responsive neurostimulation in adults with medically intractable focal onset seizures (FOS) over 9 years.

Methods: Adults treated with brain-responsive neurostimulation in 2-year feasibility or randomized controlled trials were enrolled in a long-term prospective open label trial (LTT) to assess safety, efficacy, and quality of life (QOL) over an additional 7 years. Safety was assessed as adverse events (AEs), efficacy as median percent change in seizure frequency and responder rate, and QOL with the Quality of Life in Epilepsy (QOLIE-89) inventory.

A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for Covid-19.

Background: Coronavirus disease 2019 (Covid-19) occurs after exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For persons who are exposed, the standard of care is observation and quarantine. Whether hydroxychloroquine can prevent symptomatic infection after SARS-CoV-2 exposure is unknown.

Machine Learning Methods Predict Individual Upper-Limb Motor Impairment Following Therapy in Chronic Stroke.

. Accurate prediction of clinical impairment in upper-extremity motor function following therapy in chronic stroke patients is a difficult task for clinicians but is key in prescribing appropriate therapeutic strategies. Machine learning is a highly promising avenue with which to improve prediction accuracy in clinical practice.

Spectral Content of Electroencephalographic Burst-Suppression Patterns May Reflect Neuronal Recovery in Comatose Post-Cardiac Arrest Patients.

Purpose: To assess the potential biologic significance of variations in burst-suppression patterns (BSPs) after cardiac arrest in relation to recovery of consciousness. In the context of recent theoretical models of BSP, bursting frequency may be representative of underlying network dynamics; discontinuous activation of membrane potential during impaired cellular energetics may promote neuronal rescue.

Methods: We reviewed a database of 73 comatose post-cardiac arrest patients who underwent therapeutic hypothermia to assess for the presence of BSP and clinical outcomes.

EEG Characteristics in Cooled and Rewarmed Periods in Post-cardiac Arrest Therapeutic Hypothermia Patients.

Purpose: Continuous video EEG is a tool to assess brain function in injuries, including cardiac arrest (CA). In post-CA therapeutic hypothermia (TH) studies, some EEG features are linked to poor prognosis, but the evolvement of EEG characteristics during two temperature phases and its significance is unclear. We systematically analyzed EEG characteristics in cooled and rewarmed phases of post-CA therapeutic hypothermia patients and investigated their correlation to patient outcome.

SSEP in Therapeutic Hypothermia Era.

Purpose: The reliability of somatosensory evoked potentials (SSEPs) in predicting outcome in comatose survivors of cardiac arrest treated with therapeutic hypothermia (TH) has been questioned. We investigated whether the absence of cortical (N20) responses was a reliable predictor of a nonawakening in the setting of TH.

Methods: A retrospective review was conducted in cardiac arrest survivors treated with TH admitted to a single tertiary care hospital from April, 2010 to March, 2013 who underwent SSEP testing at various time points after cardiac arrest.

Correlation analysis of [F]fluorodeoxyglucose and [F]fluoroazomycin arabinoside uptake distributions in lung tumours during radiation therapy.

Background: PET-guided dose painting (DP) aims to target radioresistant tumour regions in order to improve radiotherapy (RT) outcome. Besides the well-known [F]fluorodeoxyglucose (FDG), the hypoxia positron emission tomography (PET) tracer [F]fluoroazomycin arabinoside (FAZA) could provide further useful information to guide the radiation dose prescription. In this study, we compare the spatial distributions of FDG and FAZA PET uptakes in lung tumours.

F-Fluoroform: a F-trifluoromethylating agent for the synthesis of SCFF-aromatic derivatives.

Herein the synthesis of various SCFF-containing derivatives is reported by a transition metal-free process. By using HCFF, readily generated from a bench-stable difluoromethyl sulfonium salt, various aromatic disulfides were easily converted into the desired radiolabelled trifluoromethylthiolated compounds in the presence of a base. This protocol allowed the formation of the SCFF-containing aromatic derivatives in good to excellent radiochemical yields.

Brain-responsive neurostimulation in patients with medically intractable mesial temporal lobe epilepsy.

Objective: Evaluate the seizure-reduction response and safety of mesial temporal lobe (MTL) brain-responsive stimulation in adults with medically intractable partial-onset seizures of mesial temporal lobe origin.

Methods: Subjects with mesial temporal lobe epilepsy (MTLE) were identified from prospective clinical trials of a brain-responsive neurostimulator (RNS System, NeuroPace). The seizure reduction over years 2-6 postimplantation was calculated by assessing the seizure frequency compared to a preimplantation baseline.

Brain-responsive neurostimulation in patients with medically intractable seizures arising from eloquent and other neocortical areas.

Objective: Evaluate the seizure-reduction response and safety of brain-responsive stimulation in adults with medically intractable partial-onset seizures of neocortical origin.

Methods: Patients with partial seizures of neocortical origin were identified from prospective clinical trials of a brain-responsive neurostimulator (RNS System, NeuroPace). The seizure reduction over years 2-6 postimplantation was calculated by assessing the seizure frequency compared to a preimplantation baseline.

Evolution of [F]fluorodeoxyglucose and [F]fluoroazomycin arabinoside PET uptake distributions in lung tumours during radiation therapy.

Background: Dose painting (DP) aims to improve radiation therapy (RT) outcome by targeting radioresistant tumour regions identified through functional imaging, e.g., positron emission tomography (PET).

Radiosynthesis and validation of (±)-[18F]-3-fluoro-2-hydroxypropionate ([18F]-FLac) as a PET tracer of lactate to monitor MCT1-dependent lactate uptake in tumors.

Cancers develop metabolic strategies to cope with their microenvironment often characterized by hypoxia, limited nutrient bioavailability and exposure to anticancer treatments. Among these strategies, the metabolic symbiosis based on the exchange of lactate between hypoxic/glycolytic cancer cells that convert glucose to lactate and oxidative cancer cells that preferentially use lactate as an oxidative fuel optimizes the bioavailability of glucose to hypoxic cancer cells. This metabolic cooperation has been described in various human cancers and can provide resistance to anti-angiogenic therapies.

A Framework for Combining rTMS with Behavioral Therapy.

Upon its inception, repetitive transcranial magnetic stimulation (rTMS) was delivered at rest, without regard to the potential impact of activity occurring during or around the time of stimulation. rTMS was considered an experimental intervention imposed on the brain; therefore, the myriad features that might suppress or enhance its desired effects had not yet been explored. The field of rTMS has since grown substantially and therapeutic benefits have been reported, albeit with modest and inconsistent improvements.

DW-MRI and (18) F-FLT PET for early assessment of response to radiation therapy associated with hypoxia-driven interventions. Preclinical studies using manipulation of oxygenation and/or dose escalation.

Early markers of treatment response may help in the management of patients by predicting the outcome of a specific therapeutic intervention. Here, we studied the potential value of diffusion-weighted MRI (DW-MRI) and (18)F-fluorothymidine ((18)F-FLT), markers of cell death and cell proliferation respectively, to predict the response to irradiation. In addition, dose escalation and/or carbogen breathing were used to modulate the response to irradiation.

Long-Term Distributed Repetitive Transcranial Magnetic Stimulation for Tinnitus: A Feasibility Study.

Objectives: To assess feasibility and tolerability of long-term distributed therapeutic rTMS for refractory tinnitus, distributed over seven months.

Materials And Methods: Eight subjects with refractory tinnitus underwent five weekly sessions of 1800 pulses of 1 Hz rTMS targeted toward the temporoparietal junction. Five weeks later (study week 10), subjects meeting predefined responder criteria entered a monthly rTMS treatment phase, for the next five months.

Long-term efficacy and safety of thalamic stimulation for drug-resistant partial epilepsy.

Objective: To report long-term efficacy and safety results of the SANTE trial investigating deep brain stimulation of the anterior nucleus of the thalamus (ANT) for treatment of localization-related epilepsy.

Methods: This long-term follow-up is a continuation of a previously reported trial of 5- vs 0-V ANT stimulation. Long-term follow-up began 13 months after device implantation with stimulation parameters adjusted at the investigators' discretion.

Predictive value of (18)F-FAZA PET imaging for guiding the association of radiotherapy with nimorazole: a preclinical study.

Purpose: To assess the predictive value of hypoxia imaging by (18)F-FAZA PET in identifying tumors that may benefit from radiotherapy combined with nimorazole, a hypoxic radiosensitizer.

Material And Methods: Rats of two tumor models (Rhabdomyosarcoma and 9L-glioma) were divided into two treated groups: radiotherapy (RT) alone or RT plus nimorazole. (18)F-FAZA PET images were obtained to evaluate tumor hypoxia before the treatment.

Long-term treatment with responsive brain stimulation in adults with refractory partial seizures.

Objective: The long-term efficacy and safety of responsive direct neurostimulation was assessed in adults with medically refractory partial onset seizures.

Methods: All participants were treated with a cranially implanted responsive neurostimulator that delivers stimulation to 1 or 2 seizure foci via chronically implanted electrodes when specific electrocorticographic patterns are detected (RNS System). Participants had completed a 2-year primarily open-label safety study (n = 65) or a 2-year randomized blinded controlled safety and efficacy study (n = 191); 230 participants transitioned into an ongoing 7-year study to assess safety and efficacy.

Hypoxia-guided adaptive radiation dose escalation in head and neck carcinoma: a planning study.

Objective: To evaluate from a planning point of view the dose distribution of adaptive radiation dose escalation in head and neck squamous cell carcinoma (HNSCC) using (18)F-Fluoroazomycin arabinoside (FAZA) positron emission tomography/computed tomography (PET-CT).

Material/methods: Twelve patients with locally advanced HNSCC underwent three FAZA PET-CT before treatment, after 7 fractions and after 17 fractions of a carboplatin-5FU chemo-radiotherapy regimen (70 Gy in 2 Gy per fraction over 7 weeks). The dose constraints were that every hypoxic voxel delineated before and during treatment (newborn hypoxic voxels) should receive a total dose of 86 Gy.

Long-term repetitive transcranial magnetic stimulation therapy: new research questions arising from one tinnitus case?

Tinnitus may become refractory to treatment and disabling. Brain transcranial magnetic stimulation (TMS) has shown promise as a therapy, but has been employed primarily short-term. We treated a patient with 5 weeks of weekly repetitive TMS (rTMS), followed by 6 months of monthly rTMS.

Potential role of hypoxia imaging using (18)F-FAZA PET to guide hypoxia-driven interventions (carbogen breathing or dose escalation) in radiation therapy.

Background And Purpose: Hypoxia-driven intervention (oxygen manipulation or dose escalation) could overcome radiation resistance linked to tumor hypoxia. Here, we evaluated the value of hypoxia imaging using (18)F-FAZA PET to predict the outcome and guide hypoxia-driven interventions.

Material And Methods: Two hypoxic rat tumor models were used: rhabdomyosarcoma and 9L-glioma.

Reprogramming of tumor metabolism by targeting mitochondria improves tumor response to irradiation.

Background: The Warburg phenotype identified decades ago describes tumor cells with increased glycolysis and decreased mitochondrial respiration even in the presence of oxygen. This particular metabolism also termed 'aerobic glycolysis' reflects an adaptation of tumor cells to proliferation in a heterogeneous tumor microenvironment. Although metabolic alterations in cancer cells are common features, their impact on the response to radiotherapy is not yet fully elucidated.

[(18) F]CuCF3 : a [(18) F]trifluoromethylating agent for arylboronic acids and aryl iodides.

Positron emission tomography has emerged as the leading method for medical imaging with fluorine-18 as the most widely used radioactive isotope. Here we report a semi-automated method for the preparation of valuable [(18) F]trifluoromethylcopper, as well as its use for the radiosynthesis of [(18) F]trifluoromethylarenes and heteroarenes. Mild conditions of [(18) F]trifluoromethylation make this method particularly useful for the radiosynthesis of pharmacologically relevant [(18) F]trifluoromethylarenes and heteroarenes.

A prospective clinical study of ¹⁸F-FAZA PET-CT hypoxia imaging in head and neck squamous cell carcinoma before and during radiation therapy.

Purpose: Hypoxia in head and neck squamous cell carcinoma (HNSCC) is associated with poor prognosis and outcome. (18) F-Fluoroazomycin arabinoside (FAZA) is a positron emission tomography (PET) tracer developed to enable identification of hypoxic regions within tumor. The aim of this study was to evaluate the use of (18) F-FAZA-PET for assessment of hypoxia before and during radiation therapy.