2.

Conventional treatment for cancer routinely includes surgical resection and some combination of chemotherapy and radiation. These approaches are frequently accompanied by unintended and highly toxic collateral damage to healthy tissues, which are offset by only marginal prognostic improvements in patients with advanced cancers. This unfortunate balance has driven the development of novel therapies that aim to target tumors both safely and efficiently. Over the past decade, mounting evidence has supported the therapeutic utility of T-cell-centered cancer immunotherapy, which, in its various iterations, has been shown capable of eliciting highly precise and robust antitumor responses both in animal models and human trials. The identification of tumor-specific targets has further fueled a growing interest in T-cell therapies given their potential to circumvent the non-specific nature of traditional treatments. Of the several strategies geared toward achieving T-cell recognition of tumor, bispecific antibodies (bsAbs) represent a novel class of biologics that have garnered enthusiasm in recent years due to their versatility, specificity, safety, cost, and ease of production. Bispecific T-cell Engagers (BiTEs) are a subclass of bsAbs that are specific for CD3 on one arm and a tumor antigen on the second. As such, BiTEs function by recruiting and activating polyclonal populations of T-cells at tumor sites, and do so without the need for co-stimulation or conventional MHC recognition. Blinatumomab, a well-characterized BiTE, has emerged as a promising recombinant bscCD19×CD3 construct that has demonstrated remarkable antitumor activity in patients with B-cell malignancies. This clinical success has resulted in the rapid extension of BiTE technology against a greater repertoire of tumor antigens and the recent US Food and Drug Administration's (FDA) accelerated approval of blinatumomab for the treatment of a rare form of acute lymphoblastic leukemia (ALL). In this review, we dissect the role of T-cell therapeutics in the new era of cancer immunotherapy, appraise the value of CAR T-cells in the context of solid tumors, and discuss why the BiTE platform may rescue several of the apparent deficits and shortcomings of competing immunotherapies to support its widespread clinical application.

Objective Spinal cord stimulation (SCS) has been proven effective for multiple chronic pain syndromes. Over the past 40 years of use, the complication rates of SCS have been well defined in the literature; however, the incidence of one of the most devastating complications, spinal cord injury (SCI), remains largely unknown. The goal of the study was to quantify the incidence of SCI in both percutaneous and paddle electrode implantation. Methods We conducted a retrospective review of the Thomson Reuter's MarketScan database of all patients that underwent percutaneous or paddle SCS implantation from 2000 to 2009. The main outcome measures of the study were the incidence of SCI and spinal hematoma within 30 days following operation. Results Overall 8,326 patients met inclusion criteria for the study (percutaneous 5,458 vs. paddle: 2,868). The overall incidence of SCI was 177 (2.13%) (percutaneous: 128 (2.35%) vs. paddle: 49 (1.71%), p=0.0556). The overall incidence of spinal hematoma was 59 (0.71%) (percutaneous: 41 (0.75%) vs. paddle: 18 (0.63%), p = 0.5230). Conclusion Our study shows the overall incidence of SCI in SCS is low (2.13%) supporting that SCS is a safe procedure. No significant difference was found in the rates of SCI or spinal hematoma between the percutaneous and paddle groups. Further studies are needed to characterize the mechanisms of SCI in SCS and long-term outcomes in these patients.

Our results suggest that adenosine-assisted intracranial aneurysm surgery is not associated with an increase in perioperative cardiac complications or mortality in patients with low risk of coronary artery disease and may be considered a safe technique to assist clipping of complex aneurysms.