A Comparison of Remote and Bedside Assessment of the National Institute of Health Stroke Scale in Acute Stroke Patients.

INTRODUCTION: Telestroke videoconference for conducting the National Institute of Health Stroke Scale (NIHSS) is recommended when the facility of a direct bedside evaluation by a stroke specialist is not immediately available for hyperacute stroke assessment. However, some NIHSS-telestroke studies inherit systematic bias due to the subjective nature of NIHSS administration. We aimed to evaluate NIHSS telestroke assessment, while implementing measures to minimize subjectivity bias. PATIENTS AND METHODS: Ninety stroke patients within 48 h of onset were assessed by 6 stroke neurologists grouped in 15 pairs. Each pair of physicians assessed 6 patients. Patients were allocated through block randomization to a physician pair and order of bedside or remote assessment. Every patient was assessed once at the bedside and once remotely. Remote examination was performed by a neurologist through high-quality videoconferencing (HQ-VTC), assisted by a nurse at the patient's bedside. Kappa coefficients and the number of patients with a cumulative difference of ≤3 NIHSS points were calculated to compare bedside and remote measures. RESULTS: Cumulative difference of ≤3 NIHSS points was observed in 85.6% (95% CI 76.6-92.1%) cases. Therefore, every fifth remote examination may have been inaccurate. Quadratically weighted kappa for total NIHSS score was 0.91 (95% CI 0.87-0.95). Minimal agreements were for commands (k = 0.46), facial palsy (k = 0.43), and ataxia (k = 0.27). Remote assessments were longer than bedside: 8 min (interquartile range, IQR 7-9) vs. 6 (IQR 5-8), p < 0.001. CONCLUSIONS: NIHSS-telestroke assessment using HQ-VTC in the acute stroke settings is closely matched with NIHSS-bedside assessment but it's credibility for clinical use needs further evaluation.

Novel PD-1 inhibitor prolgolimab: expanding non-resectable/metastatic melanoma therapy choice.

BACKGROUND: Prolgolimab is an IgG1 anti-PD-1 (programmed cell death protein 1) monoclonal antibody containing the Fc-silencing 'LALA' mutation. We assessed the efficacy and safety of two dosing regimens of prolgolimab in patients with advanced melanoma in a multicenter open-label parallel-arm phase II trial (MIRACULUM). We present the final analysis after 1 year of follow-up and additional efficacy results from 2 years of follow-up. METHODS: Patients with advanced cutaneous or non-cutaneous melanoma, including stable brain metastasis, without autoimmune disease and who underwent no prior targeted therapy, anti-PD-(L)1 or anti-CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) therapy were randomly assigned (1:1) to receive prolgolimab in 2 dosing regimens, 1 mg/kg every 2 weeks (arm 1) or 3 mg/kg every 3 weeks (arm 2), until disease progression or intolerable toxicity. Randomisation was stratified based on performance status (Eastern Cooperative Oncology Group 0 or 1), lactate dehydrogenase levels (elevated or normal) and prior systemic therapy (naive or previously treated). The primary outcome was the objective response rate, assessed as per immune-related Response Evaluation Criteria in Solid Tumours by independent central review. The hypothesis that each dosing regimen of prolgolimab has an overall response rate >28% was tested independently for each study arm comprising all patients who received at least one dose of prolgolimab. Exploratory assessment of efficacy, including subgroup analysis, at 2 years of follow-up was not specified in the protocol. This study is registered withClinicalTrials.gov(NCT03269565). RESULTS: Between August 2017 and March 2018, 126 patients with advanced melanoma were enrolled. At main 1-year data cut-off, the median follow-up was 13.8 and 14.5 months in arm 1 and 2, respectively. An objective response was observed in 38.1% of patients (arm 1) and in 28.6% (arm 2). Grade III-IV treatment-related adverse events occurred in 12.7% and 3.2% of patients in arm 1 and 2, respectively. For exploratory efficacy analysis, the median follow-up was 25.4 and 25.7 months in arm 1 and 2, respectively. The 2-year progression-free survival was 33.3% in arm 1 and 30.2% in arm 2, and the 2-year overall survival was 57.1% and 46.0%, respectively. CONCLUSIONS: The MIRACULUM study met its primary end-point in both the study arms. Prolgolimab showed significant antitumour activity and a manageable safety profile in patients with advanced melanoma.

Direct electrophilic silylation of terminal alkynes.

[reaction: see text] A variety of alkynylsilanes were efficiently prepared via direct silylation of terminal alkynes with aminosilanes in the presence of zinc halides. Base- and nucleophile-sensitive functionalities were perfectly tolerated under the above reaction conditions. Initial mechanistic studies support the electrophilic character of this transformation.