Search

To develop an international consensus regarding the appropriate conditions for undertaking clinical trials in xenocorneal transplantation, here we review specific ethical, logistical, scientific, and regulatory issues regarding xenocorneal transplantation, and propose guidelines for conduct of clinical xenocorneal transplantation trials. These proposed guidelines are modeled on the published consensus statement of the International Xenotransplantation Association regarding recommended guidelines for conduct of clinical islet xenotransplantation. It is expected that this initial consensus statement will be revised over time in response to scientific advances in the field, and changes in the regulatory framework based on accumulating clinical experience. [ABSTRACT FROM AUTHOR]

Background To establish the consensus about the conditions for undertaking clinical trials in xenocorneal transplantation in Korea, specific issues regarding the xenocorneal transplantation on ethical and regulatory aspects are addressed, and the guidelines to conduct clinical trial of the xenocorneal transplantation are proposed. Method and Results Chapter 1 reviews the key ethical requirements and progress of a Korean regulatory framework for clinical trials of xenocorneal transplantation. Chapters 2-7 provide recommendations on source pigs, quality control of porcine corneal procurement, preclinical efficacy required to justify a clinical trial, strategies to prevent transmission of porcine endogenous retrovirus ( PERV), patient selection for clinical trials, and informed consent in xenocorneal transplantation using either cellularized or decellularized porcine graft, which are essentially based on the International Xenotransplantation Association ( IXA) islet xenotransplantation consensus statement. The consensus statement of the inclusion criteria for the patients' selection has been made by the executive board members in Korean External Eye Disease Society. Conclusions This consensus statement will be a good initiative for Korean Food and Drug Administration to discuss final regulatory guidelines in conducting clinical trials of xenocorneal transplantation in Korea and for International Xenotransplantation Association to develop International Consensus Standards of Xenocorneal Transplantation. [ABSTRACT FROM AUTHOR]

Abstract: Background: Ischemic lesion growth may be a surrogate marker of clinical outcome, but no such interrelationship after thrombolysis has yet been determined. We evaluated the association between early infarct growth on diffusion-weighted imaging (DWI) and long-term clinical outcome after thrombolysis. Methods: We retrospectively reviewed outcomes in patients with acute middle cerebral artery territory stroke who had been treated with intravenous tissue plasminogen activator or intra-arterial urokinase. DWI lesion volumes were measured at baseline and within 7days, and the difference was calculated. Clinical outcome was evaluated using the modified Rankin Scale (mRS) at 3months. Good and poor clinical outcomes were defined as: a) mRS 0–1 vs. mRS 2–6, b) mRS 0–2 vs. mRS 3–6, and c) responder analysis which was influenced by the baseline National Institutes of Health Stroke Scale (NIHSS) scores: good and poor outcomes were defined as mRS 0 vs. mRS 1–6 if the baseline NIHSS score was <8, mRS 0–1 vs. mRS 2–6 if the NIHSS score was 8–14, and mRS 0–2 vs. mRS 3–6 if the NIHSS score was >14. The relationship between the ischemic lesion volume change and clinical outcome was explored. The cut-off value of infarct growth predicting long-term outcome was estimated using receiver operating characteristic analysis. Results: Of the 81 patients included, 67 (82.7%) showed lesion growth, and absolute growth was significantly related to poor outcomes (P<0.001 all for mRS 2–6, mRS 3–6, and responder analysis). Multivariate analysis showed that absolute lesion growth was an independent predictor of poor outcome, defined as mRS 2–6 (P=0.002; odds ratio [OR], 1.06; 95% confidence interval [CI], 1.02–1.10), mRS 3–6 (P=0.001; OR, 1.06; 95% CI, 1.02–1.10), and poor outcome by responder analysis (P=0.001; OR, 1.06; 95% CI, 1.03–1.10). The cut-off values of lesion growth that discriminated between good and poor outcomes were 14.11cm3 for mRS 2–6; 15.87cm3 for mRS 3–6; and 14.11cm3 in responder analysis. Conclusions: Early DWI lesion growth is an independent predictor of poor outcome after thrombolysis and may serve a potential surrogate marker of clinical outcome in acute stroke trials. [Copyright &y& Elsevier]