Search

Abstract Background Recruitment of participants is the greatest risk to completion of most clinical trials, with 20–40% of trials failing to reach the targeted enrollment. This is particularly true of trials of central nervous system (CNS) therapies such as intervention for chronic stroke. The PISCES III trial was an invasive trial of stereotactically guided intracerebral injection of CTX0E03, a fetal derived neural stem cell line, in patients with chronic disability due to ischemic stroke. We report on the experience using a novel hybrid recruitment approach of a patient-facing portal to self-identify and perform an initial screen for general trial eligibility (tier 1), followed by phone screening and medical records review (tier 2) prior to a final in-person visit to confirm eligibility and consent. Methods Two tiers of screening were established: an initial screen of general eligibility using a patient-facing web portal (tier 1), followed by a more detailed screen that included phone survey and medical record review (tier 2). If potential participants passed the tier 2 screen, they were referred directly to visit 1 at a study site, where final in-person screening and consent were performed. Rates of screening were tracked during the period of trial recruitment and sources of referrals were noted. Results The approach to screening and recruitment resulted in 6125 tier 1 screens, leading to 1121 referrals to tier 2. The tier 2 screening resulted in 224 medical record requests and identification of 86 qualifying participants for referral to sites. The study attained a viable recruitment rate of 6 enrolled per month prior to being disrupted by COVID 19. Conclusions A tiered approach to eligibility screening using a hybrid of web-based portals to self-identify and screen for general eligibility followed by a more detailed phone and medical record review allowed the study to use fewer sites and reduce cost. Despite the difficult and narrow population of patients suffering moderate chronic disability from stroke, this strategy produced a viable recruitment rate for this invasive study of intracranially injected neural stem cells. Trial registration ClinicalTrials.gov Identifier: NCT03629275

Introduction Mechanical thrombectomy using stent retrievers and aspiration techniques has emerged as the standard of care for patients with acute ischemic stroke (AIS) secondary to emergent large vessel occlusion (LVO). This study intended to collect real‐world clinical evidence on the safety and effectiveness of endovascular treatment of AIS using the SOFIA Flow Plus 6F aspiration catheter. The primary endpoint was the proportion of subjects achieving mTICI ≥2b. Secondary endpoints included good functional outcomes (mRS 0‐2) at Day 90, revascularization time, first line and first pass mTICI ≥2b, occurrence of procedure‐related SAEs, vasospasm involving the accessed vascular tree, embolization to new territories (ENTs), symptomatic intracerebral hemorrhage (sICH) within 24 hours and mortality at Day 90. Methods SOFAST was a prospective, multicenter, single‐arm, observational post‐market study. The enrolled subjects were ≥21 and ≤85 years with large vessel (ICA or MCA) proximal occlusion, pre‐morbid mRS ≤1, baseline NIHSS ≥5, and for whom groin puncture was within 8 hours of symptom onset. A total of 108 patients were enrolled and treated using aspiration thrombectomy with SOFIA 6F as the first line treatment device. Patients were followed at 24 hours, 7 days/discharge, and 90 days post‐procedure. Cerebral angiography was performed pre‐ and post‐procedure. Clinical assessments included the NIHSS and mRS scales. All neurological, device‐related, and procedure‐related AEs and deaths were adjudicated by independent medical reviewers. Angiographic and other imaging data was adjudicated by an independent core laboratory. Results A total of 108 subjects were enrolled (mean age 62.7 years, 50% men) with a median NIHSS of 15.5. Of 108 subjects, 97.2% (105/108), 85.2% (92/108) and 55.6% (60/108) achieved mTICI ≥2b, ≥2c and =3 revascularization, respectively. With first line aspiration using SOFIA 6F, 87.0%, 79.6% and 52.8% achieved mTICI ≥2b, ≥2c and =3 revascularization, respectively. Median number of passes was one (range 1‐3). First pass rate of mTICI 2c or 3 using SOFIA 6F was 70.4%, of which 50.9% patients achieved mTICI score of 3. Mean duration from groin puncture to initial clot contact was 13.0 min and to successful revascularization was 17.9 min. Good functional outcome was achieved in 66.7% (72/108) of subjects at Day 90 (mRS 0‐2), procedure‐related SAEs occurred in 2.8% (3/108) of subjects and sICH in 0.9% (1/108) of subjects within 24 hours. Procedural vasospasm was recorded in in 9.3% (10/108) of subjects, and mortality in 7.4% (8/108) subjects at Day 90 (none related to the study device). No ENTs occurred. Conclusion In SOFAST study, mTICI ≥2b revascularization was achieved in the majority of patients at the end of all procedures (97.2%) and with first line treatment (87.0%) with a large fraction of these subjects achieving mTICI ≥2c following the first SOFIA 6F pass (70.4%). Durations from groin puncture to clot contact and successful revascularization were relatively short. The study presented high rates of good functional outcome at Day 90 and low rates of safety events. In summary, the study provides encouraging evidence of the safety and effectiveness of the SOFIA 6F device for aspiration thrombectomy in acute ischemic stroke subjects.

Introduction: The Neurocritical Care Society encourages an external ventricular drain (EVD) wean “as quickly as is clinically feasible” but guidelines on achieving it are limited (1). This study aims to improve quality of care by sharing a protocol to initiate EVD weaning. These criteria were developed over 7 years and showed a reduction in ventriculoperitoneal shunt/endoscopic third ventriculostomy (VPS/ETV) placement and length of stay (LOS) at our institute compared to national averages. Methods: 151 subarachnoid hemorrhage (SAH) patients from January 2016 to January 2019 were analyzed. 60 aneurysmal SAH (aSAH) and 18 non‐aneurysmal nontraumatic SAH (naSAH) patients required EVD placement. A gradual EVD weaning protocol was initiated if patients met the following criteria: the reason for EVD placement has resolved or is resolving, quantity of CSF output must be

Granular Cell Astrocytoma (GCA) is a rare astrocytic brain tumor histologically composed of plump astrocytic cells with abundant eosinophilic granular cytoplasm that exhibits immunoreactivity for GFAP and S100 proteins. It is associated with poor outcome often akin to glioblastoma despite its bland histologic appearance. We report a case of GCA in which neoplastic cells resembled macrophages on intra-operative frozen section and smear. Paraffin sections showed features of a granular cell astrocytoma, WHO grade IV, with diffuse immunohistochemical coexpression of GFAP and S100. No mutation of IDH1 or P53 was identified by immunohistochemistry; however, ATRX loss indicating mutation supported an astrocytic lineage. Additionally, sporadic weak cytoplasmic staining for CD68 and EMA and negative staining for CD163 is likely non-specific due to increased lysosomal activity and does not indicate true histiocytic or epithelial differentiation. We recommend that in the absence of overt high-grade features or admixture with conventional diffuse astrocytoma on intra-operative smear and frozen section, it may be advisable to wait to confirm the diagnosis on paraffin section histology and immunohistochemical stains before proceeding with definitive tumor resection. This diagnostic approach will prevent over-treatment by resection of non-neoplastic mimics of GCA.