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.

Patient safety and treatment outcome could be improved if physicians could rapidly control the activity of therapeutic agents in their patients. Antidote control is the safest way to regulate drug activity, because unlike rapidly clearing drugs, control of the drug activity is independent of underlying patient physiology and co-morbidities. Until recently, however, there was no general method to discover antidote-controlled drugs. Here we demonstrate that the activity and side effects of a specific class of drugs, called aptamers, can be controlled by matched antidotes in vivo. The drug, an anticoagulant aptamer, systemically induces anticoagulation in pigs and inhibits thrombosis in murine models. The antidote rapidly reverses anticoagulation engendered by the drug, and prevents drug-induced bleeding in surgically challenged animals. These results demonstrate that rationally designed drug-antidote pairs can be generated to provide control over drug activities in animals.

✓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.

Tumor histology is the most important predictor of neurological outcome after surgical resection because it predicts resectability and recurrence.

Subsidence irrespective of the measurement technique or definition does not appear to have an impact on successful fusion and/or clinical outcomes. A validated definition and standard measurement technique for subsidence is needed to determine the actual incidence of subsidence and its impact on radiographic and clinical outcomes.

Coronavirus disease 2019 (COVID-19) results from infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It was first reported in Wuhan, China in patients suffering from severe pneumonia and acute respiratory distress syndrome and has now grown into the first pandemic in over 100 years. Patients infected with SARS-CoV-2 develop arterial thrombosis including stroke, myocardial infarction and peripheral arterial thrombosis, all of which result in poor outcomes despite maximal medical, endovascular, and microsurgical treatment compared with non-COVID-19-infected patients. In this review we provide a brief overview of SARS-CoV-2, the infectious agent responsible for the COVID-19 pandemic, and describe the mechanisms responsible for COVID-19-associated coagulopathy. Finally, we discuss the impact of COVID-19 on ischemic stroke, focusing on large vessel occlusion.

Increasing serum BNP levels independently were associated with hyponatremia, significantly increased the first 24 hours after onset of delayed ischemic neurological deficits, and predicted the 2-week Glasgow Coma Scale score.