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- Poli, Sven, et al.
(author)
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Penumbral Rescue by normobaric O?=?O administration in patients with ischemic stroke and target mismatch proFile (PROOF): Study protocol of a phase IIb trial
- 2024
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In: INTERNATIONAL JOURNAL OF STROKE. - 1747-4930 .- 1747-4949. ; 19:1, s. 120-126
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Journal article (peer-reviewed)abstract
- Rationale: Oxygen is essential for cellular energy metabolism. Neurons are particularly vulnerable to hypoxia. Increasing oxygen supply shortly after stroke onset could preserve the ischemic penumbra until revascularization occurs.Aims: PROOF investigates the use of normobaric oxygen (NBO) therapy within 6 h of symptom onset/notice for brain-protective bridging until endovascular revascularization of acute intracranial anterior-circulation occlusion.Methods and design: Randomized (1:1), standard treatment-controlled, open-label, blinded endpoint, multicenter adaptive phase IIb trial.Study outcomes: Primary outcome is ischemic core growth (mL) from baseline to 24 h (intention-to-treat analysis). Secondary efficacy outcomes include change in NIHSS from baseline to 24 h, mRS at 90 days, cognitive and emotional function, and quality of life. Safety outcomes include mortality, intracranial hemorrhage, and respiratory failure. Exploratory analyses of imaging and blood biomarkers will be conducted.Sample size: Using an adaptive design with interim analysis at 80 patients per arm, up to 456 participants (228 per arm) would be needed for 80% power (one-sided alpha 0.05) to detect a mean reduction of ischemic core growth by 6.68 mL, assuming 21.4 mL standard deviation.Discussion: By enrolling endovascular thrombectomy candidates in an early time window, the trial replicates insights from preclinical studies in which NBO showed beneficial effects, namely early initiation of near 100% inspired oxygen during short temporary ischemia. Primary outcome assessment at 24 h on follow-up imaging reduces variability due to withdrawal of care and early clinical confounders such as delayed extubation and aspiration pneumonia.
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| 2. |
- Swarts, J. Douglas, et al.
(author)
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Panel 2: Eustachian Tube, Middle Ear, and Mastoid-Anatomy, Physiology, Pathophysiology, and Pathogenesis
- 2013
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In: Otolaryngology: Head and Neck Surgery. - : Wiley. - 0194-5998 .- 1097-6817. ; 148, s. 26-36
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Research review (peer-reviewed)abstract
- Objective. This report reviews the literature to identify the advances in our understanding of the middle ear (ME)Eustachian tube (ET) system during the past 4 years and, on that basis, to determine whether the short-term goals elaborated in the last report were achieved and propose updated goals to guide future otitis media (OM) research. Data Sources. Databases searched included PubMed, Web of Science (1945-present), Medline (1950 to present), Biosis Previews (1969-present), and the Zoological Record (1978 to present). The initial literature search covered the time interval from January 2007 to June 2011, with a supplementary search completed in February 2012. Review Methods. The panel topic was subdivided; each contributor performed a literature search and provided a preliminary report. Those reports were consolidated and discussed when the panel met on June 9, 2011. At that meeting, the progress was evaluated and new short-term goals proposed. Conclusions. Progress was made on 16 of the 19 short-term goals proposed in 2007. Significant advances were made in the characterization of ME gas exchange pathways, modeling ET function, and preliminary testing of treatments for ET dysfunction. Implications for Practice. In the future, imaging technologies should be developed to noninvasively assess ME/ET structure and physiology with respect to their role in OM pathogenesis. The new data derived from form/function experiments should be integrated into the finite element models and used to develop specific hypotheses concerning OM pathogenesis and persistence. Finally, rigorous studies of treatments, medical or surgical, of ET dysfunction should be undertaken.
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