Safety and feasibility of NeuroFlo use in eight- to 24-hour ischemic stroke patients.

BACKGROUND: Acute treatment of ischemic stroke patients presenting more than eight-hours after symptom onset remains limited and largely unproven. Partial aortic occlusion using the NeuroFlo catheter can augment cerebral perfusion in animals. We investigated the safety and feasibility of employing this novel catheter to treat ischemic stroke patients eight-hours to 24 h following symptom onset. METHODS: A multicenter, single-arm trial enrolled ischemic stroke patients at nine international academic medical centers. Eligibility included age 18-85 years old, National Institutes of Health stroke scale (NIHSS) score between four and 20, within eight-hours to 24 h after symptom onset, and perfusion-diffusion mismatch confirmed by magnetic resonance imaging. The primary outcome was all adverse events occurring from baseline to 30 days posttreatment. Secondary outcomes included stroke severity on neurological indices through 90 days. This study is registered with ClinicalTrials.gov, number NCT00436592. RESULTS: A total of 26 patients were enrolled. Of these, 25 received treatment (one excluded due to aortic morphology); five (20%) died. Favorable neurological outcome at 90 days (modified Rankin score 0-2 vs. 3-6) was associated with lower baseline NIHSS (P < 0·001) and with longer duration from symptom discovery to treatment. There were no symptomatic intracranial hemorrhages or parenchymal hematomas. Asymptomatic intracranial hemorrhage was visible on computed tomography in 32% and only on microbleed in another 20%. CONCLUSIONS: Partial aortic occlusion using the NeuroFlo catheter, a novel collateral therapeutic strategy, appears safe and feasible in stroke patients eight-hours to 24 h after symptom onset

Unstable particles in matter at a finite temperature: the rho and omega mesons

Unstable particles (such as the vector mesons) have an important role to play in low mass dilepton production resulting from heavy ion collisions and this has been a subject of several investigations. Yet subtleties, such as the implications of the generalization of the Breit-Wigner formula for nonzero temperature and density, e.g. the question of collisional broadening, the role of Bose enhancement, etc., the possibility of the kinematic opening (or closing) of decay channels due to environmental effects, the problem of double counting through resonant and direct contributions, are often given insufficient emphasis. The present study attempts to point out these features using the rho and omega mesons as illustrative examples. The difference between the two versions of the Vector Meson Dominance Model in the present context is also presented. Effects of non-zero temperature and density, through vector meson masses and decay widths, on dilepton spectra are studied, for concreteness within the framework of a Walecka-type model, though most of the basic issues highlighted apply to other scenarios as well.Comment: text and figures modifie

Subjective Benefits of Bimodal Listening in Cochlear Implant Recipients with Asymmetric Hearing Loss

Objective: To investigate the influence of cochlear implant (CI) use on subjective benefits in quality of life in cases of asymmetric hearing loss (AHL). Study Design: Prospective clinical trial. Setting: Tertiary academic center. Subjects and Methods: Subjects included CI recipients with AHL (n = 20), defined as moderate-to-profound hearing loss in the affected ear and mild-to-moderate hearing loss in the contralateral ear. Quality of life was assessed with the Speech, Spatial, and Qualities of Hearing Scale (SSQ) pragmatic subscales, which assess binaural benefits. Subjective benefit on the pragmatic subscales was compared to word recognition in quiet and spatial hearing abilities (ie, masked sentence recognition and localization). Results: Subjects demonstrated an early, significant improvement (P <.01) in abilities with the CI as compared to preoperative abilities on the SSQ pragmatic subscales by the 1-month interval. Perceived abilities were either maintained or continued to improve over the study period. There were no significant correlations between results on the Speech in Quiet subscale and word recognition in quiet, the Speech in Speech Contexts subscale and masked sentence recognition, or the Localization subscale and sound field localization. Conclusions: CI recipients with AHL report a significant improvement in quality of life as measured by the SSQ pragmatic subscales over preoperative abilities. Reported improvements are observed as early as 1 month postactivation, which likely reflect the binaural benefits of listening with bimodal stimulation (CI and contralateral hearing aid). The SSQ pragmatic subscales may provide a more in-depth insight into CI recipient experience as compared to behavioral sound field measures alone

Cochlear Implantation in Cases of Asymmetric Hearing Loss: Subjective Benefit, Word Recognition, and Spatial Hearing

A prospective clinical trial evaluated the effectiveness of cochlear implantation in adults with asymmetric hearing loss (AHL). Twenty subjects with mild-to-moderate hearing loss in the better ear and moderate-to-profound hearing loss in the poorer ear underwent cochlear implantation of the poorer hearing ear. Subjects were evaluated preoperatively and at 1, 3, 6, 9, and 12 months post-activation. Preoperative performance was evaluated unaided, with traditional hearing aids (HAs) or with a bone-conduction HA. Post-activation performance was evaluated with the cochlear implant (CI) alone or in combination with a contralateral HA (bimodal). Test measures included subjective benefit, word recognition, and spatial hearing (i.e., localization and masked sentence recognition). Significant subjective benefit was reported as early as the 1-month interval, indicating better performance with the CI compared with the preferred preoperative condition. Aided word recognition with the CI alone was significantly improved at the 1-month interval compared with preoperative performance with an HA and continued to improve through the 12-month interval. Subjects demonstrated early, significant improvements in the bimodal condition on the spatial hearing tasks compared with baseline preoperative performance tested unaided. The magnitude of the benefit was reduced for subjects with AHL when compared with published data on CI users with normal hearing in the contralateral ear; this finding may reflect significant differences in age at implantation and hearing sensitivity across cohorts

Effect of a 2-week interruption in methotrexate treatment on COVID-19 vaccine response in people with immune-mediated inflammatory diseases (VROOM study): a randomised, open label, superiority trial

Background: Methotrexate is the first-line treatment for immune-mediated inflammatory diseases and reduces vaccine-induced immunity. We evaluated if a 2-week interruption of methotrexate treatment immediately after COVID-19 booster vaccination improved antibody response against the S1 receptor binding domain (S1-RBD) of the SARS-CoV-2 spike protein and live SARS-CoV-2 neutralisation compared with uninterrupted treatment in patients with immune-mediated inflammatory diseases. Method: We did a multicentre, open-label, parallel-group, randomised, superiority trial in secondary-care rheumatology and dermatology clinics in 26 hospitals in the UK. Adults (aged ≥18 years) with immune-mediated inflammatory diseases taking methotrexate (≤25 mg per week) for at least 3 months, who had received two primary vaccine doses from the UK COVID-19 vaccination programme were eligible. Participants were randomly assigned (1:1) using a centralised validated computer program, to temporarily suspend methotrexate treatment for 2 weeks immediately after COVID-19 booster vaccination or continue treatment as usual. The primary outcome was S1-RBD antibody titres 4 weeks after COVID-19 booster vaccination and was assessed masked to group assignment. All randomly assigned patients were included in primary and safety analyses. This trial is registered with ISRCTN, ISRCTN11442263; following a pre-planned interim analysis, recruitment was stopped early. Finding: Between Sept 30, 2021, and March 7, 2022, we screened 685 individuals, of whom 383 were randomly assigned: to either suspend methotrexate (n=191; mean age 58·8 years [SD 12·5], 118 [62%] women and 73 [38%] men) or to continue methotrexate (n=192; mean age 59·3 years [11·9], 117 [61%] women and 75 [39%] men). At 4 weeks, the geometric mean S1-RBD antibody titre was 25 413 U/mL (95% CI 22 227–29 056) in the suspend methotrexate group and 12 326 U/mL (10 538–14 418) in the continue methotrexate group with a geometric mean ratio (GMR) of 2·08 (95% CI 1·59–2·70; p<0·0001). No intervention-related serious adverse events occurred. Interpretation: 2-week interruption of methotrexate treatment in people with immune-mediated inflammatory diseases enhanced antibody responses after COVID-19 booster vaccination that were sustained at 12 weeks and 26 weeks. There was a temporary increase in inflammatory disease flares, mostly self-managed. The choice to suspend methotrexate should be individualised based on disease status and vulnerability to severe outcomes from COVID-19. Funding: National Institute for Health and Care Research