Teprotumumab attenuates the actions of both IGF-1 and TSH in fibrocytes. Specifically, it blocks the induction of proinflammatory cytokines by TSH. These results provide, at least in part, the molecular rationale for interrogating the therapeutic efficacy of this antibody in TAO.

Object The long-term success of spinal cord stimulation is impeded by the high incidence of adverse events. The cost of complications to the healthcare budget is influenced by the time course needed to reverse the effect, and by the type of corrective measures required. Understanding the mechanism of complications and reducing them can improve the overall success rate and the cost factor. Methods The authors performed a retrospective analysis of data obtained in 160 patients treated during a 10-year period. For each category of complication, the level of healthcare resource use was assessed for each case and a unit cost was applied. The total cost of each complication was determined by summing across healthcare resource headings. All cost calculations were performed in Canadian dollars at 2005 prices. To understand the mechanics of various hardware-related complications and how to avoid them, the authors have utilized the results of bench tests conducted at Medtronic, Inc. Fifty-one adverse events occurred in 42 of the 160 patients. The complications were classified as either hardware related (39 events) or biological (12 events). The mean cost of complications during the 10-year study period was $7092 (range $130–$22,406). Conclusions Complications not only disrupt the effect of pain control but also pose an added expense to the already high cost of therapy. It is possible to reduce the complication rate, and thus improve the long-term success rate, by following the suggestions made in this paper, which are supported by the biomechanics of the human body and the implanted material.

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Purpose of Review Thyroid eye disease (TED) is a poorly understood autoimmune manifestation most commonly associated with Graves’ disease. Current nonspecific treatment paradigms offer symptomatic improvement but fail to target the underlying pathogenic mechanisms and thus, do not significantly alter the long-term disease outcome. The purpose of this review is to provide an update of the current understanding of the immunopathogenesis of TED and explore these implications for targeted immunotherapy. Recent Findings Orbital fibroblasts are integral to the pathogenesis of TED and may modulate immune responses by production of cytokines and hyaluronan in response to activation of shared autoantigens including thyrotropin receptor (TSHR) and insulin-like growth factor-1 receptor (IGF-R1). Fibrocytes share many of these phenotypic and functional features, suggesting a link between systemic and site-specific disease. Use of targeted immunotherapies in TED is limited, though data from the use Rituximab (RTX), a B cell depleting agent, are encouraging. Sustained clinical response has been seen with RTX in several reports, despite return of peripheral B cell levels to pretreatment levels. Additionally, this response appears to be independent to cytokine and antibody production, suggesting possible modulation of antigen presentation as a mechanism of its effect. Summary Progressive advances in the understanding of the immunopathogenesis of TED continue to spur clinical trials utilizing targeted immune therapies. Continued understanding of the molecular mechanisms of disease will expand potential treatments for TED patients and obviate the need for reconstructive surgical therapies.