Proteasome inhibitors (PIs) are the backbone of combination treatments for patients with multiple myeloma and AL amyloidosis, while also indicated in Waldenström\'s macroglobulinemia and other malignancies. PIs act on proteasome peptidases, causing proteome instability due to accumulating aggregated, unfolded, and/or damaged polypeptides; sustained proteome instability then induces cell cycle arrest and/or apoptosis. Carfilzomib, an intravenous irreversible PI, exhibits a more severe cardiovascular toxicity profile as compared with the orally administered ixazomib or intravenous reversible PI such as bortezomib. Cardiovascular toxicity includes heart failure, hypertension, arrhythmias, and acute coronary syndromes. Because PIs are critical components of the treatment of hematological malignancies and amyloidosis, managing their cardiovascular toxicity involves identifying patients at risk, diagnosing toxicity early at the preclinical level, and offering cardioprotection if needed. Future research is required to elucidate underlying mechanisms, improve risk stratification, define the optimal management strategy, and develop new PIs with safe cardiovascular profiles.

UNASSIGNED: Initial orthostatic hypotension is a clinically relevant syndrome in older adults which has been associated with symptoms of orthostatic intolerance. The aim of this systematic review was to determine the prevalence of orthostatic intolerance symptoms in older adults with initial orthostatic hypotension.
UNASSIGNED: MEDLINE (from 1946), EMBASE (from 1974) and Cochrane were searched to December 6th, 2019 using the terms \"initial orthostatic hypotension\", \"postural hypotension\" and \"older adults\". Study selection involved the following criteria: published in English; mean or median age ≥ 65 years and diagnosis of initial orthostatic hypotension encompassed a decrease in systolic blood pressure by ≥ 40  mmHg and/or diastolic blood pressure by ≥ 20  mmHg within a maximum of 1 min following a postural change.
UNASSIGNED: Of 8311 articles, 12 articles reporting initial orthostatic hypotension prevalence in 3446 participants with a mean age of 75 (6 SD) years (56.5% female) were included. Five initial orthostatic hypotension definition variations were utilised and symptoms were reported in six articles (968 participants, mean age 73.4 (6.1 SD) years, 56% female). The prevalence of symptoms in older adults with initial orthostatic hypotension ranged from 24 to 100% and was dependent on variations in timing or the inclusion of symptoms in the initial orthostatic hypotension definition.
UNASSIGNED: Where orthostatic intolerance symptoms were reported, a large proportion of older adults with a diagnosis of initial orthostatic hypotension were symptomatic. However, the literature on initial orthostatic hypotension and orthostatic intolerance symptoms is scarce and a variety of definitions of initial orthostatic hypotension are utilised.

UNASSIGNED: We reviewed the literature on interventions for patients with medically refractory chronically occluded internal carotid artery (COICA) to assess the risks and/or benefits after recanalization via an endovascular technique (ET) or hybrid surgery (HS, i.e., ET plus carotid endarterectomy).
UNASSIGNED: A systematic search of the electronic databases was performed. Patients with COICA were classified into 4 different categories according to Hasan et al classification.
UNASSIGNED: Eighteen studies satisfied the inclusion criteria. Only 6 studies involved an HS procedure. We identified 389 patients with COICA who underwent ET or HS; 91% were males. The overall perioperative complication rate was 10.1% (95% confidence interval [CI]: 7.4%-13.1%). For types A and B, the successful recanalization rate was 95.4% (95% CI: 86.5%-100%), with a 13.7% (95% CI: 2.3%-27.4%) complication rate. For type C, the success rate for ET was 45.7% (95% CI: 17.8%-70.7%), with a complication rate of 46.0% (95% CI: 20.0%-71.4%) for ET and for the HS technique 87.6% (95% CI: 80.9%-94.4%), with a complication rate of 14.0% (95% CI: 7.0%-21.8%). For type D, the success rate of recanalization was 29.8% (95% CI: 7.8%-52.8%), with a 29.8% (95% CI: 6.1%-56.3%) complication rate. Successful recanalization resulted in a symmetrical perfusion between both cerebral hemispheres, resolution of penumbra, normalization of the mean transit time, and improvement in Montreal Cognitive Assessment (MoCA) score (ΔMoCA = 9.80 points; P = 0.004).
UNASSIGNED: Type A and B occlusions benefit from ET, especially in the presence of a large penumbra. Type C occlusions can benefit from HS. Unfortunately, we did not identify an intervention to help patients with type D occlusions. A phase 2b randomized controlled trial is needed to confirm these findings.