Impact of operative indication and surgical complexity on outcomes after thoracic endovascular aortic repair at National Surgical Quality Improvement Program Centers

IntroductionThoracic endovascular aortic repair (TEVAR) devices are increasingly being utilized to treat aortic pathologies outside of the original Food & Drug Administration (FDA) approval for nonruptured descending thoracic aorta aneurysms (DTAs). The objective of this study was to evaluate the outcomes of patients undergoing TEVAR, elucidating the role of surgical and pathologic variables on morbidity and mortality.MethodsNational Surgical Quality Improvement Program (NSQIP) data were reviewed for all patients undergoing endovascular thoracic aorta repair from 2005 to 2007. The patients' operative indication and surgical complexity were used to divide them into study and control populations. Comorbid profiles were assessed utilizing a modified Charlson Comorbidity Index (CCI). Thirty-day occurrences of mortality and serious adverse events (SAEs) were used as study endpoints. Univariate and multivariate models were created using demographic and clinical variables to assess for significant differences in endpoints (P ≤ .05).ResultsA total of 440 patients undergoing TEVAR were identified. When evaluating patients based on operative indication, the ruptured population had increased mortality and SAE rates compared to the nonruptured DTA population (22.6% vs 6.2%;P < .01 and 35.5% vs 9.1%;P < .01, respectively). Further analysis by surgical complexity revealed increased mortality and SAE rates when comparing the brachiocephalic aortic debranching population to the noncovered left subclavian artery population (23.1% vs 6.5%; P = .02 and 30.8% vs 9.1%; P < .01, respectively). Multivariate analysis demonstrated that operative indication was not a correlate of mortality or SAEs (odds ratio [OR], 0.95; P = .92 and OR, 1.42; P = .39, respectively); however, brachiocephalic aortic debranching exhibited a deleterious effect on mortality (OR, 8.75; P < .01) and SAE rate (OR, 6.67; P = .01).ConclusionThe operative indication for a TEVAR procedure was not found to be a predictor of poor patient outcome. Surgical complexity, specifically the need for brachiocephalic aortic debranching and aortoiliac conduit, was shown to influence the occurrence of SAEs in a multivariate model. Comparative data, such as these, illustrate real-world outcomes of patients undergoing TEVAR outside of the original FDA-approved indications. This information is of paramount importance to various stakeholders, including third-party payers, the device industry, regulatory agencies, surgeons, and their patients

Design of an 8-40 GHz Antenna for the Wideband Instrument for Snow Measurements (WISM)

Measurement of land surface snow remains a significant challenge in the remote sensing arena. Developing the tools needed to remotely measure Snow Water Equivalent (SWE) is an important priority. The Wideband Instrument for Snow Measurements (WISM) is being developed to address this need. WISM is an airborne instrument comprised of a dual-frequency (X- and Ku-bands) Synthetic Aperture Radar (SAR) and dual-frequency (K- and Ka-bands) radiometer. A unique feature of this instrument is that all measurement bands share a common antenna aperture consisting of an array feed reflector that covers the entire bandwidth. This paper covers the design and fabrication of the wideband array feed which is based on tightly coupled dipole arrays. Implementation using a relatively new multi-layer microfabrication process results in a small, 6x6 element, dual-linear polarized array with beamformer that operates from 8 to 40 gigahertz

Design of an 8-40 GHz Antenna for the Wideband Instrument for Snow Measurements (WISM)

This poster describes the implementation of a 6x6 element, dual linear polarized array with beamformer that operates from about 8-40 GHz. It is implemented using a relatively new multi-layer microfabrication process. The beamformer includes baluns that feed dual-polarized differential antenna elements and reactive splitters that cover the full frequency range of operation. This fixed beam array (FBA) serves as the feed for a multi-band instrument designed to measure snow water equivalent (SWE) from an airborne platform known as the Wideband Instrument for Snow Measurements (WISM)

Progranulin is expressed within motor neurons and promotes neuronal cell survival

<p>Abstract</p> <p>Background</p> <p>Progranulin is a secreted high molecular weight growth factor bearing seven and one half copies of the cysteine-rich granulin-epithelin motif. While inappropriate over-expression of the progranulin gene has been associated with many cancers, haploinsufficiency leads to atrophy of the frontotemporal lobes and development of a form of dementia (frontotemporal lobar degeneration with ubiquitin positive inclusions, FTLD-U) associated with the formation of ubiquitinated inclusions. Recent reports indicate that progranulin has neurotrophic effects, which, if confirmed would make progranulin the only neuroprotective growth factor that has been associated genetically with a neurological disease in humans. Preliminary studies indicated high progranulin gene expression in spinal cord motor neurons. However, it is uncertain what the role of Progranulin is in normal or diseased motor neuron function. We have investigated progranulin gene expression and subcellular localization in cultured mouse embryonic motor neurons and examined the effect of progranulin over-expression and knockdown in the NSC-34 immortalized motor neuron cell line upon proliferation and survival.</p> <p>Results</p> <p><it>In situ </it>hybridisation and immunohistochemical techniques revealed that the <it>progranulin </it>gene is highly expressed by motor neurons within the mouse spinal cord and in primary cultures of dissociated mouse embryonic spinal cord-dorsal root ganglia. Confocal microscopy coupled to immunocytochemistry together with the use of a progranulin-green fluorescent protein fusion construct revealed progranulin to be located within compartments of the secretory pathway including the Golgi apparatus. Stable transfection of the human <it>progranulin </it>gene into the NSC-34 motor neuron cell line stimulates the appearance of dendritic structures and provides sufficient trophic stimulus to survive serum deprivation for long periods (up to two months). This is mediated at least in part through an anti-apoptotic mechanism. Control cells, while expressing basal levels of progranulin do not survive in serum free conditions. Knockdown of progranulin expression using shRNA technology further reduced cell survival.</p> <p>Conclusion</p> <p>Neurons are among the most long-lived cells in the body and are subject to low levels of toxic challenges throughout life. We have demonstrated that progranulin is abundantly expressed in motor neurons and is cytoprotective over prolonged periods when over-expressed in a neuronal cell line. This work highlights the importance of progranulin as neuroprotective growth factor and may represent a therapeutic target for neurodegenerative diseases including motor neuron disease.</p

The natural history of thin melanoma and the utility of sentinel lymph node biopsy

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141184/1/jso24765_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/141184/2/jso24765.pd

Dislocation interactions during low-temperature plasticity of olivine and their impact on the evolution of lithospheric strength

The strength of the lithosphere is typically modelled based on constitutive equations for steady-state flow. However, strain hardening may cause significant evolution of strength in the colder load-bearing portion of the lithosphere. Recent rheological data from low-temperature deformation experiments on olivine suggest that strain hardening occurs due to the presence of temperature-independent back stresses generated by long-range elastic interactions among dislocations. These interpretations provided the basis for a flow law that incorporates hardening by the development of back stress. Here, we test this dislocation-interaction hypothesis by examining the microstructures of olivine samples deformed plastically at room temperature either in a deformation-DIA apparatus at differential stresses of ≤4.3GPa or in a nanoindenter at applied contact stresses of ≥10.2GPa. High-angular resolution electron backscatter diffraction maps reveal the presence of geometrically necessary dislocations with densities commonly above 1014m−2 and intragranular heterogeneities in residual stress on the order of 1 GPa in both sets of samples. Scanning transmission electron micrographs reveal straight dislocations aligned in slip bands and interacting with dislocations of other types that act as obstacles. The resulting accumulations of dislocations in their slip planes, and associated stress heterogeneities, are consistent with strain hardening resulting from long-range back-stresses acting among dislocations and thereby support the form of the flow law for low-temperature plasticity. Based on these observations, we predict that back stresses among dislocations will impart significant mechanical anisotropy to deformed lithosphere by enhancing or reducing the effective stress. Therefore, strain history, with associated microstructural and micromechanical evolution, is an important consideration for models of lithospheric strength. The microstructural observations also provide new criteria for identifying the operation of back-stress induced strain hardening in natural samples and therefore provide a means to test the applicability of the flow law for low-temperature plasticity.This research was supported by Natural Environment Research Council grants NE/M000966/1 to LNH, AJW, and DW and 1710DG008/JC4 to LNH and AJW; European Plate Observing System Transnational Access grant EPOS-TNA-MSL 2018-022 to LNH; Advanced Photon Source General User Proposal 55176 to LNH, DLG, and WBD; and National Science Foundation Awards EAR-1361319 to WBD, EAR-1625032 to JMW, and EAR-1806791 to KMK

HER2/HER3 heterodimers and p21 expression are capable of predicting adjuvant trastuzumab response in HER2+ breast cancer

Human epidermal growth factor receptor 2 (HER2) plays an important role in breast cancer progression and provides predictive information for response to targeted therapy including trastuzumab although this is limited. Downstream pathways, such as PI3K/Akt, are associated with HER2/HER3 heterodimerization promoting survival and proliferation amongst cancer cells. Thus, patient outcome and trastuzumab therapy effectiveness might be further characterised by HER2/HER3 dimerisation and its signalling pathways. HER2/HER3 dimerisation status was assessed, using chromogenic in situ Proximity Ligation Assay, in two breast cancer series: early stage primary breast cancer, including 224 HER2+ patients that were not submitted to trastuzumab, and HER2+ breast cancer where patients were treated with adjuvant trastuzumab (n = 143). Levels of biomarkers including PI3K, pAKT, ER, PgR, HER3, BCL2, p53, PTEN and p21 were measured using immunohistochemistry. Levels of HER2/HER3 heterodimers were compared with biomarker expression and patient outcome. An association between high levels of HER2/HER3 dimerisation and absence of hormone receptors, ER and PgR, was observed. We further show for the first time the presence of HER2/HER3 heterodimers and the loss of p21 expression in HER2+ breast cancer predicts a significantly poorer outcome when submitted to adjuvant trastuzumab. Breast cancer patients that reveal high levels of HER2/HER3 dimerisation and loss of p21 are associated with poor survival prognosis in patients with HER2+ breast cancer treated with adjuvant trastuzumab. Further quantification analysis of HER dimer/ligand complexes and downstream signalling pathways will begin to unravel the complex associations with patient outcome and its relationship with sensitivity to targeted treatment