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Aspirin may reduce the risk of vascular graft thrombosis after cardiovascular surgery. We previously reported the 30-day results of a trial evaluating aspirin use before coronary artery surgery. Here we report the 1-year outcomes evaluating late thrombotic events and disability-free survival.Using a factorial design, we randomly assigned patients undergoing coronary artery surgery to receive aspirin or placebo and tranexamic acid or placebo. The results of the aspirin comparison are reported here. The primary 1-year outcome was death or severe disability, the latter defined as living with a modified Katz activities of daily living score 8. Secondary outcomes included a composite of myocardial infarction, stroke and death from any cause through to 1 year after surgery.Patients were randomly assigned to aspirin (1059 patients) or placebo (1068 patients). The rate of death or severe disability was 4.1% in the aspirin group and 3.5% in the placebo group (relative risk, 1.17; 95% confidence interval, 0.76-1.81; P = .48). There was no significant difference in the rates of myocardial infarction (P = .11), stroke (P = .086), or death (P = .24), or a composite of these cardiovascular end points (P = .68). With the exception of those with a low European System for Cardiac Operative Risk Evaluation score (P = .03), there were no interaction effects on these outcomes with tranexamic acid (all tests of interaction P .10).In patients undergoing coronary artery surgery, preoperative aspirin did not reduce death or severe disability, or thrombotic events through to 1 year after surgery.

Background Sutureless aortic valve replacement (SU-AVR) offers an alternative to traditional aortic valve replacement (AVR) and is becoming widely performed in many hospitals. The aim of the current study was to evaluate the early experience in SU-AVR with the Perceval S bioprosthesis at Monash Medical Centre. Methods Fifty-two (52) patients who underwent SU-AVR were retrospectively analysed (mean age: 74.8 ± 6.5 years). Data regarding preoperative and operative details, hospital stay, postoperative outcomes within 30 days after surgery, re-admissions and longer term echocardiographic data were collected from the relevant hospital databases. Results In isolated SU-AVR, the mean aortic cross-clamp and cardiopulmonary bypass times were 48.8 and 67.8 minutes, respectively. There were no deaths within 30 days after surgery. Rhythm disturbances developed in 46.2% of patients, with atrial fibrillation (32.7%) and heart block (9.6%) being most common. Mean and peak transaortic gradients reduced from 46.2 and 77.9 mmHg preoperatively, to 10.7 and 19.7 mmHg at 12 months postoperatively, respectively. Conclusions The absence of early mortality and the satisfactory clinical and haemodynamic results demonstrated the overall safety and efficacy of the Perceval S valve. Although sutureless valves seem to be a promising alternative to traditional sutured valves, the high rate of new postoperative rhythm disturbances, particularly heart block, is potentially a concern with SU-AVR.

Summary:. Optimizing preoperative planning is widely sought in deep inferior epigastric artery perforator (DIEP) flap surgery. One reason for this is that rates of fat necrosis remain relatively high (up to 35%), and that adjusting flap design by an improved understanding of individual perforasomes and perfusion characteristics may be useful in reducing the risk of fat necrosis. Imaging techniques have substantially improved over the past decade, and with recent advances in 3D printing, an improved demonstration of imaged anatomy has become available. We describe a 3D-printed template that can be used preoperatively to mark out a patient’s individualized perforasome for flap planning in DIEP flap surgery. We describe this “perforasome template” technique in a case of a 46-year-old woman undergoing immediate unilateral breast reconstruction with a DIEP flap. Routine preoperative computed tomographic angiography was performed, with open-source software (3D Slicer, Autodesk MeshMixer and Cura) and a desktop 3D printer (Ultimaker 3E) used to create a template used to mark intra-flap, subcutaneous branches of deep inferior epigastric artery (DIEA) perforators on the abdomen. An individualized 3D printed template was used to estimate the size and boundaries of a perforasome and perfusion map. The information was used to aid flap design. We describe a new technique of 3D printing a patient-specific perforasome template that can be used preoperatively to infer perforasomes and aid flap design.

Coronary artery bypass grafting (CABG) is one of the most commonly performed procedures worldwide. Its place in the treatment of coronary artery disease has been established for decades with the benefits of CABG versus percutaneous coronary intervention (PCI) in various scenarios being extensively investigated. Recent major landmark randomised clinical trials such as SYNTAX, EXCEL and NOBLE have helped to define the patients in which each approach is likely to be most successful. Indeed, the last decade has seen most centres embrace the “Heart Team” concept, whereby a collaborative approach helps to optimise patients’ outcomes.

Multiple sources of funding for research exist. Publically-funded research bodies serve as ideal starting points for investigators. A strong understanding of the research project is required prior to preparing funding applications. Grant applications must be tailored to the funding body’s priorities. An experienced, multidisciplinary team is essential for securing funding for larger, more complex research projects. Important criteria used to judge grant applications include originality, generalizability, feasibility and methodological strength in addition to the track record of the investigators.

Background Repeat cardiac surgeries are well known to have higher rates of complications, one of the important reasons being injuries associated with re-do sternotomy. Routine imaging with CT can help to minimise this risk by pre-operatively assessing the anatomical relation between the sternum and the underlying cardiovascular structures, but is limited by its inability to determine the presence and severity of functional tethering and adhesions between these structures. However, with the evolution of wide area detector MD CT scanners, it is possible to assess the presence of tethering using the dynamic four-dimensional CT (4D CT) imaging technique. Methods Nineteen patients undergoing re-do cardiac surgery were pre-operatively imaged using dynamic 4D CT during regulated respiration. The datasets were assessed in cine mode for presence of differential motion between sternum and underlying cardiovascular structures which indicates lack of significant tethering. Results Overall, there was excellent correlation between preoperative imaging and intraoperative findings. The technique enabled our surgeons to meticulously plan the procedures and to avoid re-entry related injuries. Conclusions Our initial experience shows that dynamic 4D CT is useful in risk stratification prior to re-do sternotomy by determining the presence or absence of tethering between sternum and underlying structures based on assessment of differential motion. Furthermore we determined the technique to be superior to non-dynamic assessment of retrocardiac tethering.

The delivery of healthcare that meets the requirements for quality, safety and cost-effectiveness relies on a well-trained medical workforce, including clinical academics whose career includes a specific commitment to research, education and/or leadership. In 2011, the Medical Deans of Australia and New Zealand published a review on the clinical academic workforce and recommended the development of an integrated training pathway for clinical academics. A bi-national Summit on Clinical Academic Training was recently convened to bring together all relevant stakeholders to determine how best to do this. An important part understood the lessons learnt from the UK experience after 10 years since the introduction of an integrated training pathway. The outcome of the summit was to endorse strongly the recommendations of the medical deans. A steering committee has been established to identify further stakeholders, solicit more information from stakeholder organisations, convene a follow-up summit meeting in late 2015, recruit pilot host institutions and engage the government and future funders.

Objective To assess whether introduction of universal leukodepletion (ULD) of red blood cells (RBCs) for transfusion was associated with improvements in cardiac surgery patient outcomes. Methods Retrospective study (2005-2010) conducted at 6 institutions. Associations between leukodepletion and outcomes of mortality, infection, and acute kidney injury (AKI) were modeled by logistic regression, and intensive care unit length of stay (LOS) in survivors was explored using linear regression. To examine trends over time, odds ratios (ORs) for outcomes of transfused were compared with nontransfused patients, including a comparison with nontransfused patients who were selected based on propensity score for RBC transfusion. Results We studied 14,980 patients, of whom 8857 (59%) had surgery pre-ULD. Transfusions of RBCs were made in 3799 (43%) pre-ULD, and 2525 (41%) post-ULD. Administration of exclusively leukodepleted, versus exclusively nonleukodepleted, RBCs was associated with lower incidence of AKI (adjusted OR 0.80, 95% confidence interval [CI] 0.65-0.98, P = .035), but no difference in mortality or infection. For post-ULD patients, no difference was found in mortality (OR 0.96, 95% CI 0.76-1.22, P = .76) or infection (OR 0.91, 95% CI 0.79-1.03, P = .161); however, AKI was reduced (OR 0.79 95% CI 0.68-0.92, P = .003). However, ORs for post-ULD outcomes were not significantly different in nontransfused, versus transfused, patients. Furthermore, those who received exclusively nonleukodepleted RBCs were more likely to have surgery post-ULD. Conclusions Universal leukodepletion was not associated with reduced mortality or infection in transfused cardiac surgery patients. An association was found between ULD and reduced AKI; however, this reduction was not significantly different from that seen in nontransfused patients, and other changes in care most likely explain such changes in renal outcomes.

ObjectivesTo evaluate the impact of preoperative atrial fibrillation (pre-op AF) on early and late mortality after isolated coronary artery bypass graft (CABG) surgery.MethodsData obtained prospectively between June 2001 and December 2009 by the Australasian Society of Cardiac and Thoracic Surgeons National Cardiac Surgery Database Program were retrospectively analyzed. Patients who underwent concomitant atrial arrhythmia surgery/ablation were excluded. Demographic and operative data were compared between patients with and without pre-op AF. The independent association of pre-op AF on early mortality, perioperative complications, and late mortality was determined.ResultsIsolated CABG surgery was performed in 21,534 patients; 1312 (6.1%) presented with pre-op AF. Pre-op AF patients were older (mean age, 71 years vs. 65 years, p

Acute kidney injury (AKI) is a common complication following cardiac surgery performed on cardiopulmonary bypass (CPB) and has important implications for prognosis. The aetiology of cardiac surgery-associated AKI is complex, but renal hypoxia, particularly in the medulla, is thought to play at least some role. There is strong evidence from studies in experimental animals, clinical observations and computational models that medullary ischaemia and hypoxia occur during CPB. There are no validated methods to monitor or improve renal oxygenation during CPB, and thus possibly decrease the risk of AKI. Attempts to reduce the incidence of AKI by early transfusion to ameliorate intra-operative anaemia, refinement of protocols for cooling and rewarming on bypass, optimization of pump flow and arterial pressure, or the use of pulsatile flow, have not been successful to date. This may in part reflect the complexity of renal oxygenation, which may limit the effectiveness of individual interventions. We propose a multi-disciplinary pathway for translation comprising three components. Firstly, large-animal models of CPB to continuously monitor both whole kidney and regional kidney perfusion and oxygenation. Secondly, computational models to obtain information that can be used to interpret the data and develop rational interventions. Thirdly, clinically feasible non-invasive methods to continuously monitor renal oxygenation in the operating theatre and to identify patients at risk of AKI. In this review, we outline the recent progress on each of these fronts.

Objectives This study was conducted to investigate the microbial contamination of caffeine citrate 10 mg/mL oral solution (CCOS) during a simulated in-use test in a clinical environment. Methods A real-time in-use simulation study was conducted in a neonatal intensive care unit at a UK National Health Service hospital. Following the simulation, samples of the product were taken and assessed for microbiological contamination. Results This study shows that CCOS does not comply with the European Pharmacopoeia (Ph Eur) Specification for Preservative Efficacy. However, it shows that the in-use contamination of the product in a clinical environment remained within the Ph Eur General Text (5.1.4) Specification for the Microbiological Quality of Non-Sterile Pharmaceutical Preparations. Discussion There is a requirement for medicines to be developed and formulated specifically for paediatric use. This requires that excipients should be kept to a minimum. CCOS has been specifically developed to treat apnoea of prematurity in neonates. This product does not contain antimicrobial preservatives. It is produced as a terminally sterilised solution to enable an appropriate shelf-life. CCOS is currently marketed as a unit dose product, and once opened has an immediate-use, single-patient requirement. This gives CCOS an expensive unit cost. A suitable in-use shelf-life would reduce unit dose costs. Conclusions The evidence from this study would suggest that CCOS, a product specifically formulated for use in neonates without antimicrobial preservatives, can safely be assigned a 7-day room temperature in-use shelf-life.

Objective To inform the design of a pivotal randomized controlled trial of prophylactic intra-aortic balloon counterpulsation (IABC) in patients undergoing coronary artery bypass graft (CABG) at high risk of postoperative low cardiac output syndrome (LCOS). Design Inception cohort study. Setting A total of 13 established cardiac centers in Australia, Canada, New Zealand, and the United Kingdom. Participants Adult patients were eligible for inclusion if they were listed for CABG surgery and had 2 or more LCOS risk factors (low ejection fraction, severe left main coronary artery disease, redo sternotomy, unstable angina). Interventions Outcomes of interest were a composite outcome of in-hospital mortality, postoperative acute myocardial infarction (AMI), acute kidney injury (AKI), or stroke as well as 6-month vital status and quality of life using the EuroQol 5-dimensional questionnaire (EQ5D). Measurements and Main Results The study included 136 participants over a 29-month period. Overall, in-hospital and 6-month mortality occurred in 7 (5%) and 11 (8%) participants, respectively. The composite outcome occurred in 60 (44%). The mean increase in EQ5D summary index at 6 months was 0.10 (standard deviation 0.24, p = 0.01). Perioperative AMI, AKI, or stroke significantly decreased the odds of a clinically meaningful improvement in quality of life (odds ratio 0.32; 95% confidence interval 0.13-0.79; p = 0.014). Preoperative IABC was used in 39 participants and did not predict postoperative outcomes. Conclusions The study identified a group of patients at risk of LCOS in whom CABG surgery was associated with a substantial burden of perioperative morbidity. Preoperative IABC use was variable, supporting the need for further research.

Background The inflammatory response to surgery varies considerably between individual patients. Age might be a substantial factor in this variability. Our objective was to examine the association of patient age and other potential risk factors with the occurrence of a postoperative systemic inflammatory response syndrome, during the first 24 h after cardiac surgery. Methods This was a retrospective cohort study, using linked data from the Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) Database and the Australian and New Zealand Intensive Care Society (ANZICS) Adult Patient Database. Data from patients who underwent coronary artery bypass grafting and/or valve surgery were used. The association between age and postoperative SIRS was analysed using Poisson regression, and corrected for other risk factors. Restricted cubic splines were used to determine relevant age categories. Results are expressed as risk ratios (RR) with 95% confidence intervals (CI). Results Data from 28 513 patients were used. In both univariable and multivariable models, increased patient age was strongly associated with reduced postoperative SIRS prevalence. Using 73–83 yr as the reference category, the RRs (95% CI) for the age categories were 1.38 (1.28–1.49) for ≤43 yr, 1.15 (1.09–1.20) for 44–63 yr, 1.05 (1.00–1.09) for 64–72 yr, and 1.03 (0.94–1.12) for >83 yr, respectively. The predictive value for postoperative SIRS of the final model, however, was moderate (c-statistic: 0.61). Conclusions We have demonstrated that advanced patient age is associated with a decreased risk of postoperative SIRS among cardiac surgery patients, where patients aged over 72 yr had the lowest risk.

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Background The Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) Database collects and monitors preoperative, operative, and 30-day outcome data on patients undergoing cardiac surgery, and delivers regular performance feedback reports to key personnel with intent to drive quality improvement. The current feedback approach appears to be ineffective in driving change to minimise Unit performance variation. We sought to determine the acceptability and feasibility of providing structured feedback in addition. Methods Cardiac surgeons were surveyed to assess their evaluation of the current feedback reports and assist in developing the content of structured feedback. We then assessed acceptability and performance outcomes of control Units receiving current feedback reports via email, versus intervention Units that in addition received structured feedback. Results Survey respondents assessing the current feedback report agreed that the content is relevant (95%), key performance indicators (KPIs) are useful (85%), and that it would be beneficial to compare surgeons’ KPIs (75%). Survey respondents rating method of feedback, requested structured feedback sessions one to two times annually (67%; control Units), and future structured feedback (83%; intervention Units). With combined report and structured feedback, improved performance was noted for an under-performing Unit. Limitations of feedback in driving quality improvement was high performance of Units at baseline, low surgeon participation, and scheduling challenges for structured feedback. Conclusions In this pilot study, compared to the control method, structured feedback did not significantly improve communication. To maximise quality improvement efforts, a collaborative feedback approach that fosters a climate of continuous performance improvement, is recommended.

Acute pulmonary embolism (PE) is a common condition frequently associated with a high mortality worldwide. It can be classified into non-massive, sub-massive and massive, based on the degree of haemodynamic compromise. Surgical pulmonary embolectomy, despite having been in existence for over 100 years, is generally regarded as an option of last resort, with expectedly high mortality rates. Recent advances in diagnosis and recognition of key qualitative predictors of mortality, such as right ventricular stress on echocardiography, have enabled the re-exploration of surgical pulmonary embolectomy for use in patients prior to the development of significant circulatory collapse, with promising results. We aim to review the literature and discuss the indications, perioperative workup and outcomes of surgical pulmonary embolectomy in the management of acute PE.

Single cell microinjection is widely used in biological sciences, especially in genetic engineering and cytopathology. To investigate mechanical responses of the adherent cell in microinjection, a general geometrical description of adherent cells in microinjection is proposed. Based on finite strain theory in isotropic hyperelasticity and minimal potential energy principle, a hyperelastic model of the adherent cell is developed. Factors affecting the interaction force and the stress distribution in the adherent cell penetration are revealed and analyzed. The force-deformation relationship obtained in the proposed model shows high similarity with classical Hertz model, while more detailed mechanical behaviours of the adherent cell in microinjection can be discovered from the proposed model.

Additive manufacturing was used to build a large scale prototype of a 3-DOF, 3-PRS parallel manipulator designed for enhancing the mobility of instruments used in endonasal neurosurgery. The prototype is 5 times larger than the design, with an outer diameter of 25mm. It uses custom ball and socket joints to provide pitch and roll capabilities of ±60° while remaining compact. Testing of the robots range of motion shows the desired workspace is achievable. Visual tracking was used to record the precision of this motion. Positioning errors were relatively low with a root mean squared error of 1.1°. The prototype exhibits high strength and is able to withstand axial forces of 80 N and torques up to 300 N mm. Future research will focus on the development of a 5 mm diameter manipulator.

Background: Currently, the mechanical dynamics of soft tissue deformation is achieved by numerical time integrations such as the explicit or implicit integration; however, the explicit integration is stable only under a small time step, whereas the implicit integration is computa-tionally expensive in spite of the accommodation of a large time step. Objective: This paper presents a cellular neural network method for stable simulation of soft tissue deformation dynamics. Method: The non-rigid motion equation is formulated as a cellular neural network with lo-cal connectivity of cells, and thus the dynamics of soft tissue deformation is transformed into the neural dynamics of the cellular neural network. Results: Results show that the proposed method can achieve good accuracy at a small time step. It still remains stable at a large time step, while maintaining the computational effi-ciency of the explicit integration. Conclusion: The proposed method can achieve stable soft tissue deformation with effi-ciency of explicit integration for surgical simulation.

BACKGROUND: Realistic and real-time modeling and simulation of soft tissue deformation is a fundamental research issue in the field of surgical simulation. OBJECTIVE: In this paper, a novel cellular neural network approach is presented for model-ing and simulation of soft tissue deformation by combining neural dynamics of cellular neural network with ChainMail mechanism. METHOD: The proposed method formulates the problem of elastic deformation into cellular neural network activities to avoid the complex computation of elasticity. The local position adjustments of ChainMail are incorporated into the cellular neural network as the local con-nectivity of cells, through which the dynamic behaviors of soft tissue deformation are trans-formed into the neural dynamics of cellular neural network. RESULTS: Experiments demonstrate that the proposed neural network approach is capable of modeling the soft tissues' nonlinear deformation and typical mechanical behaviors. CONCLUSIONS: The proposed method not only improves ChainMail's linear deformation with the nonlinear characteristics of neural dynamics but also enables the cellular neural net-work to follow the principle of continuum mechanics to simulate soft tissue deformation.

Summary Acute risk change has been described as the difference in calculated mortality risk between the pre-operative and postoperative periods of cardiac surgery. We aimed to assess whether this was associated with long-term survival after cardiac surgery. We retrospectively analysed 22,570 cardiac surgical patients, with minimum and maximum follow-up of 1.0 and 6.7 years. Acute risk change was calculated as the arithmetic difference between pre- and postoperative mortality risk. ‘Rising risk’ represented an increase in risk from pre- to postoperative phase. The primary outcome was one-year mortality. Secondary outcomes included mortality at 3 and 5 years and time to death. Univariable and multivariable analyses were undertaken to examine the relationship between acute risk change and outcomes. Rising risk was associated with higher mortality (5.6% vs. 3.5%, p < 0.001). After adjusting for baseline risk, rising risk was independently associated with increased 1-year mortality (OR 2.6, 95%CI 2.2–3.0, p < 0.001). The association of rising risk with long-term survival was greatest in patients with highest baseline risk. Cox regression confirmed rising risk was associated with shorter time to death (HR 1.86, 1.68–2.05, p < 0.001). Acute risk change may represent peri-operative clinical events in combination with unmeasured patient risk and noise. Measuring risk change could potentially identify patterns of events that may be amenable to investigation and intervention. Further work with case review, and risk scoring with shared variables, may identify mechanisms, including the interaction between miscalibration of risk and true differences in peri-operative care.

To use the World Health Organisation’s International Classification of Functioning to measure disability following critical illness using patient-reported outcomes. A prospective, multicentre cohort study conducted in five metropolitan intensive care units (ICU). Participants were adults who had been admitted to the ICU, received more than 24 h of mechanical ventilation and survived to hospital discharge. The primary outcome was measurement of disability using the World Health Organisation’s Disability Assessment Schedule 2.0. The secondary outcomes included the limitation of activities and changes to health-related quality of life comparing survivors with and without disability at 6 months after ICU. We followed 262 patients to 6 months, with a mean age of 59 ± 16 years, and of whom 175 (67%) were men. Moderate or severe disability was reported in 65 of 262 (25%). Predictors of disability included a history of anxiety/depression [odds ratio (OR) 1.65 (95% confidence interval (CI) 1.22, 2.23), P = 0.001]; being separated or divorced [OR 2.87 (CI 1.35, 6.08), P = 0.006]; increased duration of mechanical ventilation [OR 1.04 (CI 1.01, 1.08), P = 0.03 per day]; and not being discharged to home from the acute hospital [OR 1.96 (CI 1.01, 3.70) P = 0.04]. Moderate or severe disability at 6 months was associated with limitation in activities, e.g. not returning to work or studies due to health (P

Coordinating angiogenesis with acquisition of tissue-specific properties in endothelial cells is essential for vascular function. In the retina, endothelial cells form a blood-retina barrier by virtue of tight junctions and low transcytosis. While the canonical Norrin/Fz4/Lrp5/6 pathway is essential for angiogenesis, vascular remodeling, and barrier maturation, how these diverse processes are coordinated remains poorly understood. Here we demonstrate that Apcdd1, a negative regulator of Wnt/β-catenin signaling, is expressed in retinal endothelial cells during angiogenesis and barrier formation. Apcdd1-deficient mice exhibit a transient increase in vessel density at ages P10-P12 due to delayed vessel pruning. Moreover, Apcdd1 mutant endothelial cells precociously form the paracellular component of the barrier. Conversely, mice that overexpress Apcdd1 in retina endothelial cells have reduced vessel density but increased paracellular barrier permeability. Apcdd1 thus serves to precisely modulate Wnt/Norrin signaling activity in the retinal endothelium and coordinate the timing of both vascular pruning and barrier maturation.

Disruption of the blood-brain barrier (BBB) is a defining and early feature of multiple sclerosis (MS) that directly damages the central nervous system (CNS), promotes immune cell infiltration, and influences clinical outcomes. There is an urgent need for new therapies to protect and restore BBB function, either by strengthening endothelial tight junctions or suppressing endothelial vesicular transcytosis. Although wingless integrated MMTV (Wnt)/β-catenin signaling plays an essential role in BBB formation and maintenance in healthy CNS, its role in BBB repair in neurologic diseases such as MS remains unclear. Using a Wnt/β-catenin reporter mouse and several downstream targets, we demonstrate that the Wnt/β-catenin pathway is up-regulated in CNS endothelial cells in both human MS and the mouse model experimental autoimmune encephalomyelitis (EAE). Increased Wnt/β-catenin activity in CNS blood vessels during EAE progression correlates with up-regulation of neuronal Wnt3 expression, as well as breakdown of endothelial cell junctions. Genetic inhibition of the Wnt/β-catenin pathway in CNS endothelium before disease onset exacerbates the clinical presentation of EAE, CD4+ T-cell infiltration into the CNS, and demyelination by increasing expression of vascular cell adhesion molecule-1 and the transcytosis protein Caveolin-1 and promoting endothelial transcytosis. However, Wnt signaling attenuation does not affect the progressive degradation of tight junction proteins or paracellular BBB leakage. These results suggest that reactivation of Wnt/β-catenin signaling in CNS vessels during EAE/MS partially restores functional BBB integrity and limits immune cell infiltration into the CNS.

Rorschach inkblots have had a striking impact on the worlds of art and science because of the remarkable variety of associations with recognizable and namable objects they induce. Originally adopted as a projective psychological tool to probe mental health, psychologists and artists have more recently interpreted the variety of induced images simply as a signature of the observers' creativity. Here we analyze the relationship between the spatial scaling parameters of the inkblot patterns and the number of induced associations, and suggest that the perceived images are induced by the fractal characteristics of the blot edges. We discuss how this relationship explains the frequent observation of images in natural scenery.

Background: Few studies have addressed the effect of “trainee surgeon” status on outcomes after isolated aortic valve replacement (AVR). Methods and Results: A retrospective analysis of data, collected by the Australasian Society of Cardiac and Thoracic Surgeons Cardiac Surgery Database Program between June 2001 and December 2009 was performed. Patient demographics, intra-operative characteristics and early morbidity were compared between trainee and staff cases. Multivariate analyses were used to determine the independent association of training status with 30-day and late mortality. Isolated AVR was performed in 2747 patients; of these, 369 (13.4%) were by trainees. Compared to staff cases, trainee cases were less likely to present with renal failure (1.1% vs. 3.7%, p = 0.010) or in a critical preoperative state (1.4% vs. 3.7%, p = 0.020). The mean EuroSCORE was lower in trainee patients, compared to staff patients (8.11 ± 2.80 vs. 8.81 ± 3.09, p < 0.001). Trainee cases had longer mean perfusion (117.9 min vs. 98.9 min, p < 0.001) and cross-clamp (88.8 min vs. 73.2 min, p < 0.001) times. The incidence of early complications was similar between the two groups, except for post-operative myocardial infarction (1.1% vs. 0.3%, p = 0.008) and red blood cell transfusion (43.9 vs. 40.0%, p = 0.006). On multivariate analysis, trainee status was not associated with an increased risk of 30-day mortality (2.2% vs. 2.4%, p = 0.823). Moreover, there was no significant difference in long-term outcomes and 5-year survival was comparable in both groups (89.9% vs. 84.8%, p = 0.274). Conclusions: Isolated AVR can be safely and effectively performed by trainee surgeons who are strictly supervised in the operating theatre especially during the technically complex parts of the procedure.

Coronary artery bypass grafting (CABG) remains the most widely performed cardiac operation in the western world. Over recent decades, remarkable technical progress has been made allowing the operation to be performed with low morbidity and mortality. The large majority of CABGs are still carried out on pump utilizing the heart– lung machine. In this Review, the noncardiac complications of CABG are discussed including etiology, pathophysiology, treatment and prevention.

Comorbidities, such as diabetes, affect revascularization strategy for coronary disease. We sought to determine if the degree of renal impairment affected long-term mortality after percutaneous coronary intervention (PCI) compared to coronary artery bypass grafting (CABG) in patients with multi-vessel coronary disease (MVD).8970 patients with MVD undergoing revascularization between 2004 and 2008, in two multi-center parallel PCI and CABG Australian registries were assigned to three groups based on their estimated glomerular filtration rate (eGFR)≥60 mL/min/1.73 m2 (n=1678:839), 30-59 mL/min/1.73 m2 (n=452:226) and30 mL/min/1.73 m2 (n=74:37). We used 2:1 propensity matching to compare 3306 patients undergoing primary CABG versus PCI. Shock, myocardial infarction (MI)24 h, previous CABG, valve surgery or PCI were exclusions. Long-term mortality (mean 3.1 years) was compared with Cox-proportional hazard-adjusted modeling. Observed long-term mortality rates (CABG vs. PCI) were 4.5% vs. 4.3% p=0.84, 12.8% vs. 17.3% p=0.12, and 23.0% vs. 40.5% p=0.05 in the three strata, respectively. In patients with eGFR≥60 mL/min/1.73 m2, long-term mortality between PCI and CABG (HR 0.99, 95% CI 0.65-1.49, p=0.95) was similar. However, amongst patients with eGFR 30-59 mL/min/1.73 m2, there was a significant mortality hazard with PCI (HR 2.00, 95% CI 1.32-3.04, p=0.001). In patients with eGFR30 mL/min/1.73 m2, there was a trend for hazard with PCI (HR 1.66, 95% CI 0.80-3.46, p=0.17).Long-term mortality in MVD patients with preserved renal function was very low and similar between PCI and CABG. However there was a long-term mortality hazard associated with PCI amongst patients with moderate renal impairment.

We describe the determinants of urinary oxygen tension (Po2) and the potential for use of urinary Po2as a “physiological biomarker” of the risk of acute kidney injury (AKI) in hospital settings. We also identify knowledge gaps required for clinical translation of bedside monitoring of urinary Po2. Hypoxia in the renal medulla is a hallmark of AKI of diverse etiology. Urine in the collecting ducts would be expected to equilibrate with the tissue Po2of the inner medulla. Accordingly, the Po2of urine in the renal pelvis changes in response to stimuli that would be expected to alter oxygenation of the renal medulla. Oxygen exchange across the walls of the ureter and bladder will confound measurement of the Po2of bladder urine. Nevertheless, the Po2of bladder urine also changes in response to stimuli that would be expected to alter renal medullary oxygenation. If confounding influences can be understood, urinary bladder Po2may provide prognostically useful information, including for prediction of AKI after cardiopulmonary bypass surgery. To translate bedside monitoring of urinary Po2into the clinical setting, we require 1) a more detailed knowledge of the relationship between renal medullary oxygenation and the Po2of pelvic urine under physiological and pathophysiological conditions; 2) a quantitative understanding of the impact of oxygen transport across the ureteric epithelium on urinary Po2measured from the bladder; and 3) a simple, robust medical device that can be introduced into the bladder via a standard catheter to provide reliable and continuous measurement of urinary Po2.

Overview: Working music theater singers (MTS) typically have a heavy vocal load and little is known about their perception of vocal function. The Evaluation of the Ability to Sing Easily (EASE) was used to assess professional MTS' perceptions of current singing voice status and to compare scores across demographic and performance characteristics and to evaluate the construct validity of the EASE and its subscales (VF = Vocal Fatigue, PRI = Pathologic-Risk Indicators). Methods: Professional MTS (n = 284) completed an online survey including the EASE and two additional Vocal Concern (VC) items. Scores were compared across age, gender, whether currently working, role, perceived vocal load over the past 24 h and self-reported voice problem. Results: For the whole cohort, statistically significant differences were found on all subscales according to whether or not singers perceived themselves to have a voice problem (p < 0.001). Currently performing singers were significantly different from those not performing in a show on the EASE Total (p = 0.014) and VF (p = 0.002), but not for PRI and VC. In the currently performing singer group, significant differences were found for gender, role and perceived voice problem on the EASE Total and all subscales (p < 0.01). Significantly higher VF scores were recorded for singers with heavy vocal load (p = 0.01), but there were no differences on the EASE Total (p = 0.57), PRI (p = 0.19) or VC subscales (p = 0.53). Among these performing singers, no significant age differences were found for any EASE subscales. Conclusions: These findings provide further validation of the EASE as a useful tool for measuring singers' perceptions of vocal function and suggest that the subscales should be scored separately. Future evaluation of the EASE against objective clinical assessments (e.g., videostroboscopy) is recommended. © 2014 S. Karger AG, Basel

V. Pettilä on työryhmän ARISE Investigators jäsen. Study objective: The influence of the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) on the conduct of future sepsis research is unknown. We seek to examine the potential effect of the new definitions on the identification and outcomes of patients enrolled in a sepsis trial. Methods: This was a post hoc analysis of the Australasian Resuscitation in Sepsis Evaluation (ARISE) trial of early goal-directed therapy that recruited 1,591 adult patients presenting to the emergency department (ED) with early septic shock diagnosed by greater than or equal to 2 systemic inflammatory response syndrome criteria and either refractory hypotension or hyperlactatemia. The proportion of participants who would have met the Sepsis-3 criteria for quick Sequential Organ Failure Assessment (qS0FA) score, sepsis (an increased Sequential Organ Failure Assessment score >= 2 because of infection) and septic shock before randomization, their baseline characteristics, interventions delivered, and mortality were determined. Results: There were 1,139 participants who had a qSOFA score of greater than or equal to 2 at baseline (71.6% [95% confidence interval [Cl) 69.4% to 73.8%]). In contrast, 1,347 participants (84.7% [95% CI 82.9% to 86.4%]) met the Sepsis-3 criteria for sepsis. Only 1,010 participants were both qSOFA positive and met the Sepsis-3 criteria for sepsis (63.5% [95% CI 61.1% to 65.8%]). The Sepsis-3 definition for septic shock was met at baseline by 203 participants (12.8% [95% CI 11.2% to 14.5%]), of whom 175 (86.2% [95% CI 81.5% to 91.0%]) were also qSOFA positive. Ninety-day mortality for participants fulfilling the Sepsis-3 criteria for sepsis and septic shock was 20.4% (95% CI 18.2% to 22.5%) (274/1,344) and 29.6% (95% CI 23.3% to 35.8% [60/203]) versus 9.4% (95% CI 5.8% to 13.1%) (23/244) and 17.1% (95% CI 15.1% to 19.1% [237/1,388]), respectively, for participants not meeting the criteria (risk differences 11.0% [95% CI 6.2% to 14.8%] and 12.5% [95% CI 6.3% to 19.4%], respectively). Conclusion: Most ARISE participants did not meet the Sepsis-3 definition for septic shock at baseline. However, the majority fulfilled the new sepsis definition and mortality was higher than for participants not fulfilling the criteria. A quarter of participants meeting the new sepsis definition did not fulfill the qSOFA screening criteria, potentially limiting its utility as a screening tool for sepsis trials with patients with suspected infection in the ED. The implications of the new definitions for patients not eligible for recruitment into the ARISE trial are unknown.

AIM: Urinary oxygen tension (uPO2 ) may provide an estimate of renal medullary PO2 (mPO2 ) and thus risk of acute kidney injury (AKI). We assessed the potential for variations in urine flow and arterial PO2 (aPO2 ) to confound these estimates. METHODS: In 28 sheep urine flow, uPO2 , aPO2 and mPO2 were measured during development of septic AKI. In 65 human patients undergoing cardiac surgery requiring cardiopulmonary bypass (CPB) uPO2 and aPO2 were measured continuously during CPB, and in a subset of 20 patients, urine flow was estimated every 5 minutes. RESULTS: In conscious sheep breathing room air, uPO2 was more closely correlated with mPO2 than with aPO2 or urine flow. The difference between mPO2 and uPO2 varied little with urine flow or aPO2 . In patients, urine flow increased abruptly from 3.42 ± 0.29 mL min-1 to 6.94 ± 0.26 mL min-1 upon commencement of CPB, usually coincident with reduced uPO2 . During hyperoxic CPB high values of uPO2 were often observed at low urine flow. Low urinary PO2 during CPB (

Background Tranexamic acid reduces blood loss and transfusion requirements in cardiac surgery but may increase the risk of coronary graft thrombosis. We previously reported the 30-day results of a trial evaluating tranexamic acid for coronary artery surgery. Here we report the 1-year clinical outcomes. Methods Using a factorial design, we randomly assigned patients undergoing coronary artery surgery to receive aspirin or placebo and tranexamic acid or placebo. The results of the tranexamic acid comparison are reported here. The primary 1-year outcome was death or severe disability, the latter defined as living with a modified Katz activities of daily living score of less than 8. Secondary outcomes included a composite of myocardial infarction, stroke, and death from any cause through to 1 year after surgery. Results The rate of death or disability at 1 year was 3.8% in the tranexamic acid group and 4.4% in the placebo group (relative risk, 0.85; 95% confidence interval, 0.64-1.13; P = .27), and this did not significantly differ according to aspirin exposure at the time of surgery (interaction P = .073). The composite rate of myocardial infarction, stroke, and death up to 1 year after surgery was 14.3% in the tranexamic acid group and 16.4% in the placebo group (relative risk, 0.87; 95% CI, 0.76-1.00; P = .053). Conclusions In this trial of patients having coronary artery surgery, tranexamic acid did not affect death or severe disability through to 1 year after surgery. Further work should be done to explore possible beneficial effects on late cardiovascular events.

As long-lived post-mitotic cells, neurons employ unique strategies to resist pathogen infection while preserving cellular function. Here, using a murine model of Zika virus (ZIKV) infection, we identified an innate immune pathway that restricts ZIKV replication in neurons and is required for survival upon ZIKV infection of the central nervous system (CNS). We found that neuronal ZIKV infection activated the nucleotide sensor ZBP1 and the kinases RIPK1 and RIPK3, core components of virus-induced necroptotic cell death signaling. However, activation of this pathway in ZIKV-infected neurons did not induce cell death. Rather, RIPK signaling restricted viral replication by altering cellular metabolism via upregulation of the enzyme IRG1 and production of the metabolite itaconatemechanism of viral restriction during neur. Itaconate inhibited the activity of succinate dehydrogenase, generating a metabolic state in neurons that suppresses replication of viral genomes. These findings demonstrate an immunometabolic mechanism of viral restriction during neuroinvasive infection.

Australian and New Zealand Society of Cardiac and Thoracic Surgeons, Sydney, Australia Cardiothoracic Surgical Unit, Royal Prince Alfred Hospital; The Baird Institute; University of Sydney, Sydney, Australia Department of Cardiothoracic Surgery, Royal Melbourne Hospital; Department of Surgery, University of Melbourne Victorian Heart Centre, Epworth Hospital; Department of Cardiac Surgery, Austin Hospital; University of Melbourne, Melbourne, Australia Department of Cardiothoracic Surgery, Monash Health and Department of Surgery (Monash Medical Centre), Monash University, Clayton, Victoria, Australia Department of Cardiothoracic Surgery, Westmead Hospital, Sydney, Australia

We used a dynamic three-dimensional (3D) mapping method to model the wrist in dynamic unrestricted dart throwers motion in three men and four women. With the aid of precision landmark identification, a 3D coordinate system was applied to the distal radius and the movement of the carpus was described. Subsequently, with dynamic 3D reconstructions and freedom to position the camera viewpoint anywhere in space, we observed the motion pathways of all carpal bones in dart throwers motion and calculated its axis of rotation. This was calculated to lie in 27° of anteversion from the coronal plane and 44° of varus angulation relative to the transverse plane. This technique is a safe and a feasible carpal imaging method to gain key information for decision making in future hand surgical and rehabilitative practices.

Summary Objectives Most voice self-rating tools are disease-specific measures and are not suitable for use with healthy voice users. There is a need for a tool that is sensitive to the subtleties of a singer's voice and to perceived physical changes in the singing voice mechanism as a function of load. The aim of this study was to devise and validate a scale to assess singer's perceptions of the current status of their singing voice. Methods Ninety-five vocal health descriptors were collected from focus group interviews of singers. These were reviewed by 25 currently performing music theater (MT) singers. Based on a consensus technique, the number of descriptors was decreased to 42 items. These were administered to a sample of 284 professional MT singers using an online survey to evaluate their perception of current singing voice status. Results Principal component analysis identified two subsets of items. Rasch analysis was used to evaluate and refine these sets of items to form two 10-item subscales. Both subscales demonstrated good overall fit to the Rasch model, no differential item functioning by sex or age, and good internal consistency reliability. The two subscales were strongly correlated and subsequent Rasch analysis supported their combination to form a single 20-item scale with good psychometric properties. Conclusions The Evaluation of the Ability to Sing Easily (EASE) is a concise clinical tool to assess singer's perceptions of the current status of their singing voice with good measurement properties. EASE may prove a useful tool to measure changes in the singing voice as indicators of the effect of vocal load. Furthermore, it may offer a valuable means for the prediction or screening of singers “at risk” of developing voice disorders.

Alkaptonuria is an autosomal recessive disorder of tyrosine metabolism, which results in accumulation of unmetabolized homogentisic acid and its oxidized product in various tissues, including the heart. Cardiovascular involvement is a rare but serious complication of the disease. We present two patients who have undergone successful aortic valve replacement for alkaptonuria-associated aortic stenosis along with a review of the literature.

Natural disasters impose a significant burden on society. Current disaster training programmes do not place an emphasis on equipping surgeons with non-technical skills for disaster response. This literature review sought to identify non-technical skills required of surgeons in disaster response through an examination of four categories of literature: "disaster"; "surgical"; "organisational management"; and "interprofessional". Literature search criteria included electronic database searches, internet searches, hand searching, ancestry searching and networking strategies. Various potential non-technical skills for surgeons in disaster response were identified including: interpersonal skills such as communication, teamwork and leadership; cognitive strategies such flexibility, adaptability, innovation, improvisation and creativity; physical and psychological self-care; conflict management, collaboration, professionalism, health advocacy and teaching. Such skills and the role of interprofessionalism should be considered for inclusion in surgical disaster response training course curricula.

Background Determining admission criteria to select candidates most likely to succeed in surgical training in Australia and New Zealand has been an imprecise art with little empirical evidence informing decisions. Selection to the Royal Australasian College of Surgeons' Surgical Education and Training programme is based entirely on applicants' performance in structured curriculum vitae (CV), referees' reports and interviews. This retrospective review compared General Surgery (GS) trainees' performance in selection with subsequent performance in assessments during training. Methods Data from three cohorts of GS trainees were sourced. Scores for four selection items were compared with scores from six training assessments. Interrelationships within each of the sets of selection and assessment variables were determined. Results A single significant relationship was found between scores on the three selection tools. High scores in the CV did not correlate with higher scores in any subsequent assessments. The structured referee report score, multi-station interview score and total selection score all correlated with performance in subsequent work-based assessments and examinations. Direct observation of procedural skills (DOPS) scores appear to reflect increasing acquisition of operative skills. Performance in mini clinical examinations (Mini-CEX) was variable, perhaps reflecting limitations of this assessment. Candidates who perform well in one examination tend to perform well in all three examinations. Conclusions No selection tool demonstrated strong relationships with scores in all subsequent assessments; however referee reports, multi-station interviews and total selection scores are indicators for performance in particular assessments. This may engender confidence that candidates admitted into the GS training programme are likely to progress successfully through the programme.

Background: Robotic-assisted minimally invasive surgery systems not only have the advantages of traditional laparoscopic instruments but also have other important advantages, including restoring the surgeon's hand-eye coordination and improving the surgeon's precision by filtering hand tremors. Unfortunately, these benefits have come at the expense of the surgeon's ability to feel. Various solutions for restoring this feature have been proposed. Methods: An actuated modular force feedback-enabled laparoscopic instrument was proposed that is able to measure tip-tissue lateral interaction forces as well as normal grasping forces. The instrument has also the capability to adjust the grasping direction inside the patient body. In order to measure the interaction forces, strain gauges were employed. A series of finite element analyses were performed to gain an understanding of the actual magnitude of surface strains where gauges are applied. The strain gauge bridge configurations were calibrated. A series of experiments was conducted and the results were analysed. Results: The modularity feature of the proposed instrument makes it interchangeable between various tip types of different functionalities (e.g. cutter, grasper, dissector). Calibration results of the strain gauges incorporated into the tube and at the base of the instrument presented the monotonic responses for these strain gauge configurations. Experimental results from tissue probing and tissue characterization experiments verified the capability of the proposed instrument in measuring lateral probing forces and characterizing artificial tissue samples of varying stiffness. Conclusion: The proposed instrument can improve the quality of palpation and characterization of soft tissues of varying stiffness by restoring sense of touch in robotic assisted minimally invasive surgery operations.

BackgroundThere are limited data on the impact of smoking status on outcomes after isolated coronary artery bypass graft (CABG) surgery.MethodsData obtained prospectively between June 2001 and December 2009 by the Australian and New Zealand Society of Cardiac and Thoracic Surgeons Cardiac Surgery Database Program were retrospectively analyzed. Demographic and operative data were compared between patients who were non-smokers, previous smokers, and current smokers. The independent impact of smoking status on 14 short-term complications and long-term mortality was determined using binary logistic and Cox regression, respectively.ResultsIsolated CABG surgery was performed in 21 534 patients; smoking status was recorded in 21486 (99.8%). Of these, 7023 (32.6%) had no previous smoking history, 11183 (59.1%) were previous smokers, and 3290 (15.2%) were current smokers. The 30-day mortality rate was 1.8% in non-smokers, 1.5% in previous smokers, and 1.5% in current smokers (p=NS). The incidence of peri-operative complications was generally similar in the three groups, but current smokers were at an increased risk of pneumonia (p

Background. The effect of coronary artery bypass grafting (CABG) operations on cognition was examined after controlling for the operation, emotional state, preexisting cognitive impairment, and repeated experience with cognitive tests. Methods. On-pump CABG patients (n 16), thoracic surgical patients (n 15), and a nonsurgical control group (n 15) were tested preoperatively, and at 1 and 8 weeks postoperatively, using a battery of cognitive tests and an emotional state assessment. Patient groups were similar in age, sex, level of education, and premorbid intelligence quotient score. Surgical group data were normalized against data from the nonsurgical control group before statistical analysis. Results. CABG patients performed worse on every subtest before the operation, and this disadvantage persisted after the operation. Anxiety, depression, and stress were associated with impaired cognitive performance in the surgical groups 1 week after the operation: 44% of CABG patients and 33% of surgical control patients were significantly impaired; yet, by 8 weeks, nearly all patients had recovered to preoperative levels, with 25% of CABG and 13% of surgical control patients improving beyond their preoperative performance. Conclusions. Stress, anxiety, and depression impair cognitive performance in association with CABG and thoracic operations. Most patients recover to, or exceed, preoperative levels of cognition within 8 weeks. Thus, after controlling for nonsurgical factors, the prospects of a tangible improvement in cognition after CABG are high.