Blog Archive

Αλέξανδρος Γ. Σφακιανάκης

Thursday, June 2, 2022

The microbiome of cryospheric ecosystems

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Hippocampal avoidance prophylactic cranial irradiation (HA-PCI) for small cell lung cancer reduces hippocampal atrophy compared to conventional PCI

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Abstract
Background
Reducing radiation dose to the hippocampus with hippocampal avoidance prophylactic cranial irradiation (HA-PCI) is proposed to prevent cognitive decline. It has, however, not been investigated whether hippocampal atrophy is actually mitigated by this approach. Here, we determined whether HA-PCI reduces hippocampal atrophy. Additionally we evaluated neurotoxicity of (HA-)PCI to other brain regions. Finally, we evaluated associations of hippocampal atrophy and brain neurotoxicity with memory decline.
Methods
High quality research MRI scans were acquired in the multicenter, randomized phase 3 trial NCT01780675. Hippocampal atrophy was evaluated 4 months (57 HAPCI patients and 46 PCI patients) and 12 months (28 HAPCI patients and 27 PCI patients) after (HA-)PCI. We additionally studied multimodal indices of brain injury. Memory was assessed with the Hopkins Verbal Learning Test Revised (HVLT-R).
Results
HA-PCI r educed hippocampal atrophy at 4 months (1.8% for HA-PCI and 3.0% for PCI) and at 12 months (3.0% for HA-PCI and 5.8% for PCI). Both HA-PCI and PCI were associated with considerable reductions of gray matter and normal appearing white matter, increases of white matter hyperintensities and brain aging. There were no significant associations between hippocampal atrophy and memory.
Conclusions
HA-PCI reduces hippocampal atrophy at 4 and 12 months compared to regular PCI. Both types of radiotherapy are associated with considerable brain injury. We did not find evidence for excessive brain injury after HA-PCI relative to PCI. Hippocampal atrophy was not associated with memory decline in this population as measured with HVLT-R. The usefulness of HA-PCI is still subject to debate.
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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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Differences in Fine Particle Exposure and Estimated Pulmonary Ventilation Rate with Respect to Work Tasks of Wildland Firefighters at Prescribed Burns: A Repeated Measures Study

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Abstract
Wildland firefighters (WLFFs) are exposed to a mixture of chemicals found in wildland fire smoke and emissions from nonwildland-fuel smoke sources such as diesel. We investigated compositional differences in exposure to particulate matter and explored differences in ventilation rate and potential inhaled dose relative to the work tasks of WLFFs. Repeated measures on ten professional and two volunteer firefighters were collected on prescribed burn and nonburn days. Personal monitoring consisted of real-time and gravimetric fine particulate matter (PM2.5), carbon monoxide (CO), and accelerometer measurements to estimate ventilation rate and potential dose of PM2.5. The fine particulate matter was analyzed for levoglucosan (LG) and light absorbing carbon as a surrogate for black carbon (BC). Breathing zone personal exposure concentrations of PM2.5, LG, BC, and CO were higher on burn days (P < 0.05). Differences in exposure concentrations were observed between burn day tasks (P < 0.05) with firefighters managing fire boundaries (holders) being exposed to higher CO and LG concentrations and less BC concentrations than those conducting lighting (lighters). While no statistical difference in PM2.5 exposure measures was observed between the two tasks, holders in the study tended to be exposed to higher PM2.5 concentrations (~1.4×), while lighters tended to have more inhaled amounts of PM2.5 (~1.3×). Our findings demonstrate possible diversity in the sources of particulate matter exposure at the fireline and suggest the potential importance of using dose as a metric of inhalation exposure in occupational or other settings.
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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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First case of human Brucella canis infection in the Netherlands

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Abstract
A patient was diagnosed with B. canis following exposure to infected dogs in her breeding facility. Transboundary spread of B. canis trough (illegal) import of infected dogs to non-endemic countries in Europe suggest that B. canis infection should be considered in European patients with occupational exposure to dogs.
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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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