Numerous nucleic acid ligands, also termed decoys or aptamers, have been developed during the past 15 years that can inhibit the activity of many pathogenic proteins. Two of them, Macugen and E2F decoy, are in phase III clinical trials. Several properties of aptamers make them an attractive class of therapeutic compounds. Their affinity and specificity for a given protein make it possible to isolate a ligand to virtually any target, and adjusting their bioavailability expands their clinical utility. The ability to develop aptamers that retain activity in multiple organisms facilitates preclinical development. Antidote control of aptamer activity enables safe, tightly controlled therapeutics. Aptamers may prove useful in the treatment of a wide variety of human maladies, including infectious diseases, cancer, and cardiovascular disease. We review the observations that facilitated the development of this emerging class of therapeutics, summarize progress to date, and speculate on the eventual utility of such agents in the clinic.

Aptamers are single-stranded nucleic acid molecules that bind to and inhibit proteins and are commonly produced by systematic evolution of ligands by exponential enrichment (SELEX). Aptamers undergo extensive pharmacological revision, which alters affinity, specificity, and therapeutic half-life, tailoring each drug for a specific clinical need. The first therapeutic aptamer was described 25 years ago. Thus far, one aptamer has been approved for clinical use, and numerous others are in preclinical or clinical development. This review presents a short history of aptamers and SELEX, describes their pharmacological development and optimization, and reviews potential treatment of diseases including visual disorders, thrombosis, and cancer.

Whether the large effect size of endovascular thrombectomy (EVT) for stroke due to large-vessel occlusion applies to stroke due to medium-vessel occlusion is unclear. In a multicenter, prospective, randomized, open-label trial with blinded outcome evaluation, we assigned patients with acute ischemic stroke due to medium-vessel occlusion who presented within 12 hours from the time that they were last known to be well and who had favorable baseline noninvasive brain imaging to receive EVT plus usual care or usual care alone. The primary outcome was the modified Rankin scale score (range, 0 [no symptoms] to 6 [death]) at 90 days, reported as the percentage of patients with a score of 0 or 1. A total of 530 patients from five countries were enrolled between April 2022 and June 2024, with 255 patients assigned to the EVT group and 275 to the usual-care group. Most patients (84.7%) had primary occlusions in a middle-cerebral-artery branch. A modified Rankin scale score of 0 or 1 at 90 days occurred in 106 of 255 patients (41.6%) in the EVT group and in 118 of 274 (43.1%) in the usual-care group (adjusted rate ratio, 0.95; 95% confidence interval [CI], 0.79 to 1.15; P = 0.61). Mortality at 90 days was 13.3% in the EVT group and 8.4% in the usual-care group (adjusted hazard ratio, 1.82; 95% CI, 1.06 to 3.12). Symptomatic intracranial hemorrhage occurred in 14 of 257 patients (5.4%) in the EVT group and in 6 of 272 (2.2%) in the usual-care group. Endovascular treatment for acute ischemic stroke due to medium-vessel occlusion within 12 hours did not lead to better outcomes at 90 days than usual care. (Funded by the Canadian Institutes for Health Research and Medtronic; ESCAPE-MeVO ClinicalTrials.gov number, NCT05151172.).

✓In this paper the authors review the literature concerning de novo cavernoma formation after radiation treatment. PubMed and MEDLINE database searches were performed. Data were compiled on all patients in whom de novo cavernomas formed after radiation treatment and whose cases were reported in the literature. The authors found reports in the literature of 76 patients in whom cavernomas formed de novo after radiation treatment. The mean age of the patients was 11.7 years, and the majority of these lesions occurred in males. The patients received a mean radiation dose of 60.45 Gy. The mean latency period before detection of the cavernoma was 8.9 years, and most of these lesions were detected incidentally. In symptomatic patients, the most common presenting symptoms were seizures. Thirty-seven of the patients had evidence of hemorrhage, and 54% of these required surgical intervention. De novo formation of cavernomas after radiation treatment is a relatively rare phenomenon. Patients in whom these cavernomas develop need to be followed closely because there is a propensity for the lesions to hemorrhage. Surgical intervention to treat symptomatic lesions has a favorable outcome.

OBJECTIVE:. Serum brain natriuretic peptide (BNP) is elevated after subarachnoid hemorrhage (SAH), causes diuresis and natriuresis (cerebral salt wastin