Effect of an individualized versus standard blood pressure management during mechanical thrombectomy for anterior ischemic stroke: the DETERMINE randomized controlled trial.

BACKGROUND: Hypotension and blood pressure (BP) variability during endovascular therapy (EVT) for acute ischemic stroke (AIS) due to an anterior large vessel occlusion (LVO) is associated with worse outcomes. However, the optimal BP threshold during EVT is still unknown given the lack of randomized controlled evidence. We designed the DETERMINE trial to assess whether an individualized BP management during EVT could achieve better functional outcomes compared to a standard BP management. METHODS: The DETERMINE trial is a multicenter, prospective, randomized, controlled, open-label, blinded endpoint clinical trial (PROBE design). AIS patients with a proximal anterior LVO are randomly assigned, in a 1:1 ratio, to an experimental arm in which mean arterial pressure (MAP) is maintained within 10% of the first MAP measured before EVT, or a control arm in which systolic BP (SBP) is maintained within 140-180 mm Hg until reperfusion is achieved or artery closure in case of EVT failure. The primary outcome is the rate of favorable functional outcomes, defined by a modified Rankin Scale (mRS) between 0 and 2 at 90 days. Secondary outcomes include excellent outcome and ordinal analysis of the mRS at 90 days, early neurological improvement at 24 h (National Institutes of Health Stroke Scale), final infarct volume, symptomatic intracranial hemorrhage rates, and all-cause mortality at 90 days. Overall, 432 patients will be included. DISCUSSION: DETERMINE will assess the clinical relevance of an individualized BP management before reperfusion compared to the one size fits all approach currently recommended by international guidelines. TRIAL REGISTRATION: ClinicalTrials.gov , NCT04352296. Registered on 20th April 2020.

Psychosocial and clinical factors of probands impacting intrafamilial disclosure and uptake of genetic testing among families with BRCA1/2 or MMR gene mutations.

OBJECTIVE: Intrafamilial disclosure of hereditary cancer predisposition in BRCA1/2 and mismatch repair gene (MMR) syndromes allows appropriate prevention strategies in at-risk relatives. We previously showed in a nationwide study that the uptake of genetic targeted testing (GTT) in these families was only 30%. We aimed to identify the clinical and psychosocial factors affecting the probands' intrafamilial disclosure and relatives' uptake of GTT in BRCA1/2 or MMR syndromes. METHODS: We assessed clinical variables, family history, and psychosocial variables of probands (depressive symptoms, anxiety, alexithymia, optimism, coping, family relationship, perception of cancer risks, and of hereditary transmission), together with disclosure and uptake of GTT within 103 French BRCA1/2 or MMR families. RESULTS: Among relatives eligible for GTT, 68% were informed of the predisposition, and 37% underwent GTT, according to probands' reports. Intrafamilial disclosure was inversely associated with the degree of kinship (P < .01). In multivariable analysis, disclosure increased with time since probands' genetic diagnosis (P < .01) and probands' feeling of family cohesion (0.01). GTT uptake increased with probands' depressive symptoms (0.02) and decreased with probands' perception of cancer risks (0.03). BRCA1/2 and MMR groups did not differ concerning family information and GTT uptake. CONCLUSIONS: This study identified factors affecting disclosure to relatives and GTT uptake in BRCA1/2 and MMR syndromes and gives new insights to improve probands' follow-up and intrafamilial sharing of genetic information.