Table_1_Assessing the diagnostic accuracy of CT perfusion: a systematic review.docx

Background and purposeComputed tomography perfusion (CTP) has successfully extended the time window for reperfusion therapies in ischemic stroke. However, the published perfusion parameters and thresholds vary between studies. Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses of Diagnostic Test Accuracy Studies (PRISMA-DTA) guidelines, we conducted a systematic review to investigate the accuracy of parameters and thresholds for identifying core and penumbra in adult stroke patients.MethodsWe searched Medline, Embase, the Cochrane Library, and reference lists of manuscripts up to April 2022 using the following terms “computed tomography perfusion,” “stroke,” “infarct,” and “penumbra.” Studies were included if they reported perfusion thresholds and undertook co-registration of CTP to reference standards. The quality of studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool and Standards for Reporting of Diagnostic Accuracy (STARD) guidelines.ResultsA total of 24 studies were included. A meta-analysis could not be performed due to insufficient data and significant heterogeneity in the study design. When reported, the mean age was 70.2 years (SD+/−3.69), and the median NIHSS on admission was 15 (IQR 13–17). The perfusion parameter identified for the core was relative cerebral blood flow (rCBF), with a median threshold of ConclusionA single threshold and parameter may not always accurately differentiate penumbra from core and oligemia. Further refinement of parameters is needed in the current era of reperfusion therapy.</p

Phase I trial outcome of amnion cell therapy in patients with ischemic stroke (I-ACT)

BackgroundWe proposed a Phase I dose escalation trial to assess the safety of allogeneic human amniotic epithelial cells (hAECs) in stroke patients with a view to informing the design for a Phase II trial.MethodsThe design is based on 3 + 3 dose escalation design with additional components for measuring MR signal of efficacy as well as the effect of hAECs (2–8 × 106/kg, i.v.) on preventing immunosuppression after stroke.ResultsEight patients (six males) were recruited within 24 h of ischemic stroke onset and were infused with hAECs. We were able to increase the dose of hAECs to 8 × 106 cells/kg (2 × 106/kg, n = 3; 4 × 106/kg, n = 3; 8 × 106/kg, n = 2). The mean age is 68.0 ± 10.9 (mean ± SD). The frequencies of hypertension and hyperlipidemia were 87.5%, diabetes was 37.5%, atrial fibrillation was 50%, ischemic heart disease was 37.5% and ever-smoker was 25%. Overall, baseline NIHSS was 7.5 ± 3.1, 7.8 ± 7.2 at 24 h, and 4.9 ± 5.4 at 1 week (n = 8). The modified Rankin scale at 90 days was 2.1 ± 1.2. Supplemental oxygen was given in five patients during hAEC infusion. Using pre-defined criteria, two serious adverse events occurred. One patient developed recurrent stroke and another developed pulmonary embolism whilst in rehabilitation. For the last four patients, infusion of hAECs was split across separate infusions on subsequent days to reduce the risk for fluid overload.ConclusionOur Phase I trial demonstrates that a maximal dose of 2 × 106/kg hAECs given intravenously each day over 2 days (a total of 4 × 106/kg) is safe and optimal for use in a Phase II trial.Clinical trial registrationClinicalTrials.gov, identifier ACTRN12618000076279P