A Gardening Session Turns Into a Life Threatening Aortic Transection.

Penetrating injuries to the sub-diaphragmatic aorta are challenging, with high mortality rates. Most penetrating aortic trauma results from gunshots or stab wounds. This case reports a successful aortic bypass, following partial aortic transection caused by an accidental fall on a utility knife. A healthy 82 year old woman was admitted to the emergency department following penetrating abdominal trauma following an accidental fall on an 18 cm long utility knife. On admission, the patient was haemodynamically stable, with no neurological deficit. Computed tomography angiography revealed multiple abdominal injuries to the stomach, duodenum, L4-L5 left vertebrae, and infrarenal abdominal aorta. The patient underwent urgent midline laparotomy, followed by successful aortic repair using a 14 mm polyester graft. The gastric and duodenal lesions were repaired with an omental patch. The post-operative course was uneventful. Penetrating abdominal trauma with visceral lesions and aortic transection are high risk injuries, albeit rarely described in the literature. A low threshold for imaging, and multidisciplinary management by vascular and visceral surgeons are essential for timely recognition and successful intervention

Dexamethasone for the treatment of established postoperative nausea and vomiting: A randomised dose finding trial.

Dexamethasone is widely used for the prevention of postoperative nausea and vomiting (PONV) but little is known about its efficacy for the treatment of established PONV. To test the antiemetic efficacy of intravenous dexamethasone for the treatment of established PONV in adults undergoing surgery under general anaesthesia and to determine whether there is dose-responsiveness. The DexPonv trial is a multicentre, placebo-controlled, randomised, double-blind, dose-finding study. Inclusion of patients was between September 2012 and November 2017. Follow-up for PONV symptoms was for 24 h. Thirty days postoperatively, patients were contacted by study nurses for any information on postoperative bleeding and infection. Four public hospitals in Switzerland. A total of 803 adults scheduled for elective surgery without any antiemetic prophylaxis signed the consent form; 714 were included. Among those, 319 had PONV and 281 patients were eventually randomised (intention to treat population and safety set). The per protocol set consisted of 260 patients. Patients with PONV symptoms (including retching) were randomised to a single intravenous dose of dexamethasone 3, 6 or 12 mg or matching placebo. The primary endpoint was the absence of further nausea or vomiting (including retching), within 24 h after administration of the study drug. Dexamethasone was ineffective during the first 24 h, whatever the dosage, compared to placebo, even when the model was adjusted for known risk factors (P = 0.170). There were no differences in the time to treatment failure or the quality of sleep during the first night. There was a positive correlation between the dose of dexamethasone and blood glucose concentrations (P < 0.001), but not with bleeding risk, wound infections or other adverse effects. This randomised trial failed to show anti-emetic efficacy of any of the tested intravenous regimens of dexamethasone for the treatment of established PONV in adults undergoing surgery under general anaesthesia. clinicaltrials.gov (NCT01975727)

Paclitaxel-Coated Balloon for the Treatment of Infrainguinal Disease: 12-Month Outcomes in the All-Comers Cohort of BIOLUX P-III Global Registry

Purpose: To further investigate the safety and performance of the Passeo-18 Lux drug-coated balloon (DCB) for the treatment of atherosclerotic infrainguinal disease under real-world conditions. Materials and Methods: BIOLUX P-III is an international, prospective, observational registry (ClinicalTrials.gov identifier NCT02276313) conducted at 41 centers in Europe, Asia, and Australia with follow-up visits at 6, 12, and 24 months. Of 700 patients (mean age 70.0\ub110.2 years; 439 men) with 863 lesions in the all-comers cohort, 330 (47.1%) patients had diabetes and 234 (37.7%) had chronic limb-threatening ischemia. The majority (79.3%) of lesions were in the femoropopliteal segment; of all lesions, 645 (74.9%) were calcified and 99 (11.5%) had in-stent restenosis (ISR). The mean lesion length was 84.7\ub173.3 mm. The primary clinical endpoint was major adverse events (MAEs) within 6 months, a composite of device- and procedure-related mortality through 30 days, major target limb amputation, and clinically-driven target lesion revascularization (TLR). The primary performance endpoint was clinically-driven TLR within 12 months. Results: At 6 and 12 months, freedom from MAEs was 94.0% and 89.5% in the all-comers cohort: 95.0% and 91.2% in the femoropopliteal group and 95.3% and 88.0% in the ISR subgroup, respectively. Freedom from clinically-driven TLR at 12 months was 93.1% in the all-comers cohort, 93.9% in the femoropopliteal lesions, and 89.4% for ISR lesions. All-cause mortality was 6.1% in the all-comers cohort: 5.9% in both the femoropopliteal and ISR subgroups. There were no device- or procedure-related deaths at up to 12 months. The Rutherford category improved in >80% of all subgroups at 12 months. Conclusion: In a real-world patient population, the safety and performance of the Passeo-18 Lux DCB for the treatment of atherosclerotic infrainguinal lesions are maintained, with good performance outcomes and low complication rates at 12 months

Long-term follow-up of surgically excluded popliteal artery aneurysms with multi-slice CT angiography and Doppler ultrasound

The purpose of this study was to evaluate the role of multi-slice computed tomography (MSCT) angiography in the follow-up of popliteal artery aneurysms (PAAs) that have been operated on. Aneurysm exclusion and progression, graft patency and graft-related complications were analyzed. Fourteen patients with 21 surgically excluded PAAs were evaluated with MSCT angiography with slice thickness of 1.25 mm. The mean follow-up time was 67 months. MSCT demonstrated blood flow in six non-excluded PAAs (24%), with an average increase in the diameter of 21 mm over time. Fifteen PAAs demonstrated no blood flow and revealed an average decrease of 7 mm in diameter. The origin of this residual perfusion was demonstrated, and collaterals were involved in five of six non-excluded PAAs. In addition, MSCT demonstrated three graft stenoses. Furthermore, two occluded grafts were visualized. Twenty-four percent of the patients after surgical exclusion of PAAs revealed residual perfusion within the aneurysmal sac during follow-up, with a significant increase in the aneurysmal size with MSCT. Moreover, evaluation of the graft patency could also be done as could demonstration of anastomotic abnormalities. Thus, MSCT might be considered as a new tool to evaluate residual collateral feeding of popliteal aneurysmal sac and could be useful in identification and localization of feeding vessels

Amino Acid Restriction Triggers Angiogenesis via GCN2/ATF4 Regulation of VEGF and H2S Production

Angiogenesis, the formation of new blood vessels by endothelial cells (ECs), is an adaptive response to oxygen/nutrient deprivation orchestrated by vascular endothelial growth factor (VEGF) upon ischemia or exercise. Hypoxia is the best-understood trigger of VEGF expression via the transcription factor HIF1 alpha. Nutrient deprivation is inseparable from hypoxia during ischemia, yet its role in angiogenesis is poorly characterized. Here, we identified sulfur amino acid restriction as a proangiogenic trigger, promoting increased VEGF expression, migration and sprouting in ECs in vitro, and increased capillary density in mouse skeletal muscle in vivo via the GCN2/ATF4 amino acid starvation response pathway independent of hypoxia or HIF1 alpha. We also identified a requirement for cystathionine-gamma-lyase in VEGF-dependent angiogenesis via increased hydrogen sulfide (H2S) production. H2S mediated its proangiogenic effects in part by inhibiting mitochondrial electron transport and oxidative phosphorylation, resulting in increased glucose uptake and glycolytic ATP production.11Ysciescopu

An Early Study on the Mechanisms that Allow Tissue-Engineered Vascular Grafts to Resist Intimal Hyperplasia

Intimal hyperplasia is one of the prominent failure mechanisms for arteriovenous fistulas and arteriovenous access grafts. Human tissue-engineered vascular grafts (TEVGs) were implanted as arteriovenous grafts in a novel baboon model. Ultrasound was used to monitor flow rates and vascular diameters throughout the study. Intimal hyperplasia in the outflow vein of TEVGs was assessed at the anastomosis and at juxta-anastomotic regions via histological analysis, and was compared to intimal hyperplasia with polytetrafluoroethylene (PTFE) grafts in the baboon model and in literature reports from other animal models. Less venous intimal hyperplasia was observed in histological sections with arteriovenous TEVGs than with arteriovenous PTFE grafts. TEVGs were associated with a mild, noninflammatory intimal hyperplasia. The extent of intimal tissue that formed with TEVG placement correlated with the rate of blood flow through tissue engineered vascular grafts at 2 weeks postimplant. Outflow vein dilatation was observed with increased flow rate. Both mid-graft flow rates and outflow vein diameters reached a plateau by week 4, which suggested that venous remodeling and intimal hyperplasia largely occurred within the first 4 weeks of implant in the baboon model. Given their compliant and noninflammatory nature, TEVGs appear resistant to triggers for venous intimal hyperplasia that are common for PTFE arteriovenous grafts, including (1) abundant proinflammatory macrophage populations that are associated with PTFE grafts and (2) compliance mismatch between PTFE grafts and the outflow vein. Our findings suggest that arteriovenous TEVGs develop only a mild form of venous intimal hyperplasia, which results from the typical hemodynamic changes that are associated with arteriovenous settings

Styrene maleic acid recovers proteins from mammalian cells and tissues while avoiding significant cell death.

Detection of protein biomarkers is an important tool for medical diagnostics, typically exploiting concentration of particular biomarkers or biomarker release from tissues. We sought to establish whether proteins not normally released by living cells can be extracted without harming cells, with a view to extending this into biomarker harvest for medical diagnosis and other applications. Styrene maleic acid (SMA) is a polymer that extracts nanodiscs of biological membranes (containing membrane proteins) from cells. Hitherto it has been used to harvest SMA-lipid-membrane protein particles (SMALP) for biochemical study, by destroying the living cellular specimen. In this study, we applied SMA at low concentration to human primary cardiovascular cells and rat vascular tissue, to 'biopsy' cell proteins while avoiding significant reductions in cell viability. SMA at 6.25 parts per million harvested proteins from cells and tissues without causing significant release of cytosolic dye (calcein) or reduction in cell viability at 24 and 72 hours post-SMA (MTT assay). A wide range of proteins were recovered (20-200 kDa) and a number identified by mass spectrometry: this confirmed protein recovery from plasma membrane, intracellular membranes and cell cytosol without associated cell death. These data demonstrate the feasibility of non-lethally sampling proteins from cells, greatly extending our sampling capability, which could yield new physiological and/or pathological biomarkers

The Governance of Global Innovation Systems: Putting Knowledge in Context

Technological innovation increasingly depends on multiscalar actor networks and institutions. However, the developers of many conceptual frameworks explaining innovation success have paid only limited attention to this new reality, due to their focus on regions and countries as agents that shape innovation governance and as containers that provide institutional conditions for innovation success. In particular, innovation systems literature has been criticized in this respect. In the present chapter, we refer to the recently formulated Global Innovation Systems approach, which enables researchers to capture the emergence of system resources across spatial scales. With this framework, we emphasize that beyond the focus on knowledge generation processes, a better understanding of valuation processes is necessary to guide governance structures for generating new technologies and products. This is particularly true for sectors that are oriented towards confronting grand challenges, such as cleantech industries