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Πέμπτη 2 Ιουνίου 2022

The microbiome of cryospheric ecosystems

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Identification of exosomal hsa-miR-483-5p as a potential biomarker for hepatocellular carcinoma via microRNA expression profiling of tumor-derived exosomes

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Publication date: Available online 1 June 2022

Source: Experimental Cell Research

Author(s): Jie Lin, Wansong Lin, Yannan Bai, Yanling Liao, Qiaoyan Lin, Lingfeng Chen, Yijuan Wu

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Phase II study of alisertib as a single agent for treating recurrent or progressive atypical teratoid/rhabdoid tumor

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Abstract
Background
Recurrent atypical teratoid/rhabdoid tumor (AT/RT) is, most often, a fatal pediatric malignancy with limited curative options.
Methods
We conducted a phase II study of Aurora kinase A inhibitor alisertib in patients aged <22 years with recurrent AT/RT. Patients received alisertib once daily (80 mg/m 2 as enteric-coated tablets or 60 mg/m 2 as liquid formulation) on Days 1–7 of a 21-day cycle until progressive disease (PD) occurred. Alisertib plasma concentrations were measured in cycle 1 on Days 1 (single dose) and 7 (steady state) and analyzed with noncompartmental pharmacokinetics. Trial efficacy end point was ≥10 participants with stable disease (SD) or better at 12 weeks.
Results
SD (n=8) and partial response (PR) (n=1) were observed among 30 evaluable patients. Progression-free survival (PFS) was 30.0% ± 7.9% at 6 months and 13.3% ± 5.6% at 1 year. One-year overa ll survival (OS) was 36.7% ± 8.4%. Two patients continued treatment for >12 months. PFS did not differ by AT/RT molecular groups. Neutropenia was the most common adverse effect (n=23/30, 77%). The 22 patients who received liquid formulation had a higher mean maximum concentration (Cmax) of 10.1 ± 3.0 µM and faster time to Cmax (Tmax = 1.2 ± 0.7 h) than those who received tablets (Cmax = 5.7 ± 2.4 µM, Tmax = 3.4 ± 1.4 h).
Conclusions
Although the study did not meet pre-determined efficacy end point, single agent alisertib was well tolerated by children with recurrent AT/RT, and SD or PR was observed in approximately a third of the patients.
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Overexpression of TIGAR and HO-1 in peripheral blood mononuclear cells (PBMCs) of breast cancer patients treated with radiotherapy

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Dedicated isotropic 3-D T1 SPACE sequence imaging for radiosurgery planning improves brain metastases detection and reduces the risk of intracranial relapse

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Publication date: Available online 2 June 2022

Source: Radiotherapy and Oncology

Author(s): Tugce Kutuk, Kevin J. Abrams, Martin C. Tom, Muni Rubens, Haley Appel, Charif Sidani, Matthew D. Hall, Ranjini Tolakanahalli, D. Jay J. Wieczorek, Alonso N. Gutierrez, Michael W. McDermott, Manmeet S. Ahluwalia, Minesh P. Mehta, Rupesh Kotecha

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Depolarization of echo chambers by random dynamical nudge

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Effectiveness of Paxlovid in Reducing Severe COVID-19 and Mortality in High Risk Patients

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Abstract
Background
Paxlovid was granted emergency use authorization for the treatment of mild to moderate COVID-19, based on the interim analysis of EPIC-HR trial. Paxlovid effectiveness needs to be assessed in a noncontrolled setting. In this study we used population-based real world data to evaluate the effectiveness of Paxlovid.
Methods
The database of the largest healthcare provider in Israel was used to identify all adults aged 18 years or older with first ever positive test for SARS-CoV-2 between January and February 2022, who were at high risk for severe COVID-19 and had no contraindications for Paxlovid use. Patients were included irrespective of their COVID-19 vaccination status. Cox hazard regression was used to estimate the 28 day HR for severe COVID-19 or mortality with Paxlovid examined as time-dependent variable.
Results
Overall, 180,351 eligible were included, of them only 4,737 (2.6%) were treated with Paxlovid , and 135,482 (75.1%) had adequate COVID-19 vaccination status. Both Paxlovid and adequate COVID-19 vaccination status were associated with significant decrease in the rate of severe COVID-19 or mortality with adjusted HR 0.54 (95% CI, 0.39-0.75) and 0.20 (95% CI, 0.17-0.22), respectively. Paxlovid appears to be more effective in older patients, immunosuppressed patients, and patients with underlying neurological or cardiovascular disease (interaction p-value <0.05 for all). No significant interaction was detected between Paxlovid treatment and COVID-19 vaccination status.
Conclusions
This study suggests that in the era of omicron and in real life setting Paxlovid is highly effective in reducing the risk of severe COVID-19 or mortality.
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