Depth prediction of nanotags in tissue using surface enhanced spatially offset Raman scattering (SESORS)

A model for the prediction of the depth of two ‘flavours’ of surface enhanced Raman scattering (SERS) active nanotags embedded within porcine tissue is demonstrated using ratiometric analysis of the nanotag and tissue intensities in spatially offset Raman spectroscopy (SORS) measurements.

USP Standardized Mixtures of Bovine, Ovine and Porcine Heparin Exhibit Comparable Biologic Effects to Referenced Single Sourced Heparins and May be Interchangeable,

Introduction: Unfractionated heparin (UFH) is the first line anticoagulant for the management of medical indications. UFH complexes with antithrombin to produce strong inhibition of thrombin and factor Xa. The UFHs are standardized using USP compliant amidolytic anti-Xa and IIa methods in defined conditions. Clinically used UFH is solely sourced from porcine mucosal tissue. Because of the shortage of porcine tissue and the African Swine Fever, the supply chain of this anticoagulant is compromised. Thus, there is a need for resourcing of this anticoagulant. Bovine and ovine mucosal sources represent alternate material for production of UFH. Previous studies have shown that bovine and ovine UFH exhibit anticoagulant effects which can be standardized by using the USP method. Additionally, the standardized heparins from various sources can be blended and their potency can be adjusted to exhibit comparable effects as the single sourced UFH. The purpose of this study is to evaluate the pharmacologic profile of the blended heparin and compare these activities to that of the single sourced porcine, ovine and bovine heparins. Methods: Two groups of heparins were evaluated in this study, porcine, ovine, bovine, and the blended heparin in gravimetric measurements (ug/ml) and these same four in potency adjusted measurements (U/ml). The pharmacologic profiles of the heparins in this study were investigated via global anticoagulant assays and anti-protease assays performed in plasma. Clot based assays such as the activated partial thromboplastin time (aPTT) and thrombin time (TT) were used to study the anticoagulant effects of the single source and blended heparins. The amidolytic anti-Xa and IIa assays were used to assess the inhibitory effects of these heparins on these proteases. USP compliant anti-Xa and IIa assays were used to determine potencies of the various heparins. Protamine sulfate (PS) neutralization studies were performed to evaluate the reversal of anticoagulant effects in each of the heparins. Results: The aPTT assay showed that at final concentrations of 5 ug/ml and 2.5 ug/ml porcine heparin significantly (p < .01) prolonged the aPTT compared to ovine, bovine, and blended heparins. When studied with potency adjusted heparins, all heparins demonstrated comparable aPTT values at all concentrations (U/ml). The TT assay showed that porcine and ovine heparins prolonged the TT at 1.25 ug/ml compared to bovine and blended heparins. When studied with potency adjusted heparins, all heparins demonstrated comparable TT values at all concentrations (U/ml). The anti-Xa assay showed that at all final concentrations between 10 ug/ml and 0.625 ug/ml porcine, ovine, and blended heparins produced significantly (p <.001) stronger Xa inhibition than bovine heparin. When studied with potency adjusted heparins, all heparins demonstrated comparable anti-Xa inhibition at all concentrations (U/ml). The anti-IIa assay showed that at final concentrations 2.5 ug/ml, 1.25 ug/ml, and 0.625 ug/ml porcine and ovine heparins produced significantly (p < .05) stronger IIa inhibition than bovine heparin. When studied with potency adjusted heparins, all heparins demonstrated comparable anti-IIa inhibition at all concentrations (U/ml). The USP compliant anti-Xa assay with gravimetric heparins showed potencies of 201, 201, 150, and 184 U for porcine, ovine, bovine, and blended heparins respectively. The USP compliant anti-Xa assay with potency adjusted heparins showed comparable potencies for all four heparins. The USP compliant anti-IIa assay with gravimetric heparins showed potencies of 204, 196, 127, and 167 U for porcine, ovine, bovine, and blended heparins respectively. The USP compliant anti-IIa assay with potency adjusted heparins showed comparable potencies for all four heparins. The protamine sulfate neutralization studies demonstrated complete neutralization at all concentrations for all of the potency adjusted heparins in the aPTT, TT, anti-Xa, and anti-IIa assays. Conclusion: These studies support the hypothesis that a blended heparin product from bovine, ovine, and porcine tissue, when standardized in USP unit-equivalent proportions, exhibits a comparable anticoagulant profile to the single species heparins. These findings suggest that there is a potential for development of blended heparin to stabilize supply chain of this important anticoagulant and warrant clinical validation. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Thermal Evaluation of a Micro-Coaxial Antenna Set to Treat Bone Tumors: Design, Parametric FEM Modeling and Evaluation in Multilayer Phantom and Ex Vivo Porcine Tissue

Bone cancer is rare in adults, the most affected persons by this disease are young people and children. The common treatments for bone cancer are surgery, chemotherapy, and targeted therapies; however, all of them have side-effects that decrease the patient’s quality of life. Thermotherapy is one of the most promising treatments for bone cancer; its main goal is to increase the tumor temperature to kill cancerous cells. Although some micro-coaxial antennas have been used to treat bone tumors, most of them are designed to treat soft tissue. Therefore, the purpose of this work is to analyze the thermal behavior of four micro-coaxial antennas specifically designed to generate thermal ablation in bone tissue to treat bone tumors, at 2.45 GHz. The proposed antennas were the metal-tip monopole (MTM), the choked metal-tip monopole (CMTM), the double slot (DS) and the choked double slot (CDS). The design and optimization of the antennas by using the Finite Element Method (FEM) allow to predict the optimal antenna dimensions and their performance when they are in contact with the affected biological tissues (bone, muscle, and fat). In the FEM model, a maximum power transmission was selected as the main parameter to choose the optimum antenna design, i.e., a Standing Wave Ratio (SWR) value around 1.2–1.5. The four optimized antennas were constructed and experimentally evaluated. The evaluation was carried out in multilayer phantoms (fat, muscle, cortical, and cancellous bone) and ex vivo porcine tissue at different insertion depths of the antennas. To fully evaluate the antennas performance, the standing wave ratio (SWR), power loss, temperature profiles, and thermal distributions were analyzed. In the experimentation, the four antennas were able to reach ablation temperatures (>60 °C) and the highest reached SWR was 1.7; the MTM (power loss around 16%) and the CDS (power loss around 6.4%) antennas presented the lowest SWR values depending on the antenna insertion depth, either in multilayer tissue phantom or in ex vivo tissue. These proposed antennas allow to obtain ablation temperatures with an input power of 5 W after 5 min of treatment; these values are lower than the ones reported in the literature.

Characterizing the Material Properties of the Kidney and Liver in Unconfined Compression and Probing Protocols with Special Reference to Varying Strain Rate

The liver and kidneys are the most commonly injured organs due to traumatic impact forces applied to the abdomen and pose a challenge to physicians due to a hard-to-diagnose risk of internal bleeding. A better understanding of the mechanism of injury will improve diagnosis, treatment, forensics, and other fields. Finite element modelling is a tool that can aid in this understanding, but accurate material properties are required including the strain rate dependency and the feasibility of using animal tissue properties instead of human. The elastic modulus in a probing protocol and the elastic modulus, failure stress, and failure strain in a compression protocol were found for both liver and kidney tissue from human and porcine specimens at varying strain rates. Increases in the elastic modulus were seen for both the human kidney and liver, but only for the porcine kidney, when comparing the unconfined compression and probing protocols. A strain rate dependency was found for both the liver and kidney properties and was observed to have a larger saturation effect at higher rates for the failure stress than for the elastic modulus. Overall, the material properties of intact liver and kidney were characterized, and the strain rate dependency was numerically modelled. The study findings suggest that some kidney and liver material properties vary from human to porcine tissue. Therefore, it is not always appropriate to use material properties of porcine tissue in computational or physical models of the human liver and kidney.

Large-gap Peripheral Nerve Repair Using Xenogeneic Transplants in Primates

Early surgical intervention is required to successfully treat severe, large-gap peripheral nerve injuries. However, all existing treatments have shortcomings, and for large-gap injuries (≥4 cm), there is no reported alternative to autologous nerve. We report preclinical repair of large (4 cm), complete transectional radial nerve damage in Rhesus macaques using viable, whole sciatic nerve from genetically engineered, designated pathogen free porcine donors. Porcine nerves are physiologically similar to human nerves, contain neurotrophic growth factors and a matrix-rich scaffold, and offer greater clinical availability. We demonstrate regeneration of the transected nerve, distal muscle reinnervation, and recovery of conduction velocity and compound muscle action potential across xenogeneic transplants resulting in functional recovery comparable to autologous controls. We also show the lack of systemic porcine cell migration and the elimination of detectable transplanted porcine tissue. Our findings support the safety and efficacy of neural porcine therapeutics and the broader clinical potential of xenotransplantation.

Ex Vivo Determination of Broadband Absorption and Effective Scattering Coefficients of Porcine Tissue

A novel approach for precise determination of the optical scattering and absorption properties of porcine tissue using an optimized integrating sphere setup was applied. Measurements on several sample types (skin, muscle, adipose tissue, bone, cartilage, brain) in the spectral range between 400 nm and 1400 nm were performed. Due to the heterogeneity of biological samples, measurements on different individual animals as well as on different sections for each sample type were carried out. For all samples, we used an index matching method to reduce surface roughness effects and to prevent dehydration. The derived absorption spectra were used to estimate the concentration of important tissue chromophores such as water, oxy- and deoxyhemoglobin, collagen and fat.

Surgically generated aerosol and mitigation strategies: combined use of irrigation, respirators and suction massively reduces particulate matter aerosol

Background Aerosol is a health risk to theatre staff. This laboratory study quantifies the reduction in particulate matter aerosol concentrations produced by electrocautery and drilling when using mitigation strategies such as irrigation, respirator filtration and suction in a lab environment to prepare for future work under live OR conditions. Methods We combined one aerosol-generating procedure (monopolar cutting or coagulating diathermy or high-speed diamond- or steel-tipped drilling of cadaveric porcine tissue) with one or multiple mitigation strategies (instrument irrigation, plume suction and filtration using an FFP3 respirator filter) and using an optical particle counter to measure particulate matter aerosol size and concentrations. Results Significant aerosol concentrations were observed during all aerosol-generating procedures with concentrations exceeding 3 × 106 particles per 100 ml. Considerable reductions in concentrations were observed with mitigation. In drilling, suction, FFP3 filtration and wash alone respectively reduced aerosol by 19.3–31.6%, 65.1–70.8% and 97.2 to > 99.9%. The greatest reduction (97.38 to > 99.9%) was observed when combining irrigation and filtration. Coagulating diathermy reduced concentrations by 88.0–96.6% relative to cutting, but produced larger particles. Suction alone, and suction with filtration reduced aerosol concentration by 41.0–49.6% and 88.9–97.4% respectively. No tested mitigation strategies returned aerosol concentrations to baseline. Conclusion Aerosol concentrations are significantly reduced through the combined use of filtration, suction and irrigation. Further research is required to characterise aerosol concentrations in the live OR and to find acceptable exposure limits, and in their absence, to find methods to further reduce exposure to theatre staff.

Monitoring deep-tissue oxygenation with a millimeter-scale ultrasonic implant

Deep tissue oxygenation monitoring has many potential applications. Vascular complications after solid organ transplantation, for example, frequently lead to graft ischemia, dysfunction or loss, and can occur months after transplantation. While imaging approaches can provide intermittent assessments of graft perfusion, they require highly skilled practitioners, and fail to directly assess graft oxygenation. Existing tissue oxygen monitoring systems have many drawbacks, including the need for wired connections, the inability to provide real-time data, and, crucially, an operation that is limited to surface tissues. Here, we present the first wireless, minimally-invasive deep tissue oxygen monitoring system that provides continuous real-time data from centimeter-scale depths in a clinically-relevant large animal (sheep) model and demonstrates operation at great depths (up to 10 cm) through ex vivo porcine tissue. The system relies on a millimeter-sized, wireless, battery-free, implantable luminescence oxygen sensor that is powered by ultrasound and capable of bi-directional data transfer with an external transceiver. We present various aspects of system and sensor performance and demonstrate the operation of the system in vitro in distilled water, phosphate-buffered saline (PBS) and undiluted human serum, ex vivo through porcine tissue, and in vivo in a sheep model. We believe this technology represents a new class of diagnostic system particularly suitable for organ monitoring, as well as other surgical or critical care indications.