Background Activating variants in platelet‐derived growth factor receptor beta (PDGFRB), including a variant we have previously described (p.Tyr562Cys [g.149505130T>C [GRCh37/hg19]; c.1685A>G]), are associated with development of multiorgan pathology, including aneurysm formation. To investigate the association between the allele fraction genotype and histopathologic phenotype, we performed an expanded evaluation of post‐mortem normal and aneurysmal tissue specimens from the previously published index patient. Methods and Results Following death due to diffuse subarachnoid hemorrhage in a patient with mosaic expression of the above PDGFRB variant, specimens from the intracranial, coronary, radial and aortic arteries were harvested. DNA was extracted and alternate allele fractions (AAF) of PDGFRB were determined using digital droplet PCR. Radiographic and histopathologic findings, together with genotype expression of PDGFRB were then correlated in aneurysmal tissue and compared to non‐aneurysmal tissue. The PDGFRB variant was identified in the vertebral artery, basilar artery, and P1 segment aneurysms (AAF: 28.7%, 16.4%, and 17.8%, respectively). It was also identified in the coronary and radial artery aneurysms (AAF: 22.3% and 20.6%, respectively). In phenotypically normal intracranial and coronary artery tissues, the PDGFRB variant was not present. The PDGFRB variant was absent from lymphocyte DNA and normal tissue, confirming it to be a non‐germline somatic variant. Primary cell cultures from a radial artery aneurysm localized the PDGFRB variant to CD31‐, non‐endothelial cells. Conclusions Constitutive expression of PDGFRB within the arterial wall is associated with the development of human fusiform aneurysms. The role of targeted therapy with tyrosine kinase inhibitors in fusiform aneurysms with PDGFRB mutations should be further studied.

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INTRODUCTION:The Affordable Care Act expanded Medicaid eligibility in many states, improving access to some forms of elective healthcare in the United States. Whether this effort increased access to elective spine surgical care is unknown.METHODS: We evaluated elective spine surgeries using state inpatient databases from 2011-2016 from 10 states that did and four states that did not expand Medicaid access in 2014. Patients aged 18-64 years undergoing elective spine surgery were included. We used a quasiexperimental difference-in-difference design to evaluate the impact of CLINICAL NEUROSURGERY

BackgroundMajor challenges to T cell engager drugs are antigen loss and adaptive resistance, often in the form of PDL1 upregulation on cancer cells or the tumor microenvironment. Engaged T cells are dependent on cancer cell co-stimulation, and synaptic engagements that may deteriorate the function of the effector T cell compartment.MethodsGuidance and Navigation Control (GNC) drugs are multi-specific cell engagers. This platform of GNC T cell engagers is designed to mediate direct cytolysis of cancer cells by T cells, and influence the outcome of synaptic engagement, overcome PDL1 resistance, and respond to biological signals in the tumor microenvironment to increase functional potency. GNC that bind tumor antigens, CD3, 4-1BB and PDL1 are designed to redirect T cells toward tumor antigens and engage PDL1 as a target antigen.ResultsT cell activation resulting from tumor associated antigen and CD3/41BB binding, results in IFN-gamma release. The local IFN-gamma upregulates PDL1 on cancer cells, increasing the antigen density and converting a major mechanism of adaptive resistance into local drug sensitivity. This novel design and first-in-class mechanism of action may reduce resistance mediated by both antigen loss, and immune suppression through cytolysis of PDL1 expressing cells within the tumor microenvironment.ConclusionsKnowledge of PDL1 regulation and its role as a universal target in the solid tumor microenvironment provides one path forward for multi-modal T cell engagers with potential for broad clinical efficacy. Multi-specific GNC demonstrated preclinical functionality, and developability. GNC T cell engagers targeting tumor associated and tumor specific antigens are currently in Phase I trials for solid and liquid cancer indications.1 2ReferencesA Study of GNC-038, a Tetra-specific Antibody, in Participants With R/R Non-Hodgkin Lymphoma. ClinicalTrials.gov Identifier: NCT04606433.A Study of GNC-039, a Tetra-specific Antibody, in Participants With Relapsed/Refractory or Metastatic Solid Tumors. ClinicalTrials.gov Identifier: NCT04794972.