Simulated Thrombin Generation in the Presence of Surface-Bound Heparin and Circulating Tissue Factor

An expanded computational model of surface induced thrombin generation was developed that includes hemodynamic effects, 22 biochemical reactions and 44 distinct chemical species. Surface binding of factors V, VIII, IX, and X was included in order to more accurately simulate the formation of the surface complexes tenase and prothrombinase. In order to model these reactions, the non-activated, activated and inactivated forms were all considered. This model was used to investigate the impact of surface bound heparin on thrombin generation with and without the additive effects of thrombomodulin (TM). In total, 104 heparin/TM pairings were evaluated (52 under venous conditions, 52 under arterial conditions), the results demonstrating the synergistic ability of heparin and TM to reduce thrombin generation. Additionally, the role of circulating tissue factor (TF[subscript p]) was investigated and compared to that of surface-bound tissue factor (TF[subscript s]). The numerical results suggest that circulating TF has the power to amplify thrombin generation once the coagulation cascade is already initiated by surface-bound TF. TF[subscript p] concentrations as low as 0.01 nM were found to have a significant impact on total thrombin generation.National Institutes of Health (U.S.) (Grants HL106018 and HL56819

Health research improves healthcare: now we have the evidence and the chance to help the WHO spread such benefits globally

There has been a dramatic increase in the body of evidence demonstrating the benefits that come from health research. In 2014, the funding bodies for higher education in the UK conducted an assessment of research using an approach termed the Research Excellence Framework (REF). As one element of the REF, universities and medical schools in the UK submitted 1,621 case studies claiming to show the impact of their health and other life sciences research conducted over the last 20 years. The recently published results show many case studies were judged positively as providing examples of the wide range and extensive nature of the benefits from such research, including the development of new treatments and screening programmes that resulted in considerable reductions in mortality and morbidity. Analysis of specific case studies yet again illustrates the international dimension of progress in health research; however, as has also long been argued, not all populations fully share the benefits. In recognition of this, in May 2013 the World Health Assembly requested the World Health Organization (WHO) to establish a Global Observatory on Health Research and Development (R&D) as part of a strategic work-plan to promote innovation, build capacity, improve access, and mobilise resources to address diseases that disproportionately affect the world’s poorest countries. As editors of Health Research Policy and Systems (HARPS), we are delighted that our journal has been invited to help inform the establishment of the WHO Global Observatory through a Call for Papers covering a range of topics relevant to the Observatory, including topics on which HARPS has published articles over the last few months, such as approaches to assessing research results, measuring expenditure data with a focus on R&D, and landscape analyses of platforms for implementing R&D. Topics related to research capacity building may also be considered. The task of establishing a Global Observatory on Health R&D to achieve the specified objectives will not be easy; nevertheless, this Call for Papers is well timed – it comes just at the point where the evidence of the benefits from health research has been considerably strengthened

Left subclavian artery coverage during thoracic endovascular aortic repair and risk of perioperative stroke or death

IntroductionLeft subclavian artery (LSA) coverage during thoracic endovascular aortic repair (TEVAR) is often necessary due to anatomic factors and is performed in to up to 40% of procedures. Despite the frequency of LSA coverage during TEVAR, reported associations with risk of periprocedural stroke or death are inconsistent in reported literature. We examined the 2005-2008 American College of Surgeons National Surgical Quality Improvement Program Participant Use Data file to determine associations between LSA coverage during TEVAR and risk of perioperative stroke or death.MethodsCurrent procedural terminology (CPT) codes were used to identify patients undergoing TEVAR, LSA coverage, and subclavian revascularization. Patients undergoing coronary bypass, ascending aortic repair, abdominal aortic aneurysm repair, or nonvascular intra-abdominal procedures during the same operation were excluded. Perioperative stroke and mortality associations with LSA coverage were examined using logistic regression models for each outcome. Significance was assessed at α = 0.05, with univariable P < .05 required for multivariable model entry.ResultsEight hundred forty-five TEVAR procedures were identified, of which 52 patients were excluded due to additional major procedures performed with TEVAR. Seven hundred thirty-three of the remaining 793 procedures included CPT codes indicating primary placement of an initial thoracic endograft and form the basis of this analysis. LSA coverage occurred in 279 procedures (38%). Thirty-day stroke and mortality rates were 5.7% and 7.0%, respectively. LSA coverage was associated with increased 30-day risk of stroke in multivariable modeling (odds ratio [OR], 2.17 95% confidence interval [CI], 1.13-4.14; P = .019). Other significant multivariable risk factors for stroke included proximal aortic cuff placement during TEVAR (OR, 2.58; 95% CI, 1.30-5.16; P = .007) and emergency procedure status (OR, 3.60; 95% CI, 1.87-6.94; P < .001). No significant association between LSA coverage and perioperative mortality was identified (univariable OR, 1.70; 95% CI, 0.98-2.93; P = .0578).ConclusionLSA coverage during thoracic endovascular repair is associated with increased risk of perioperative stroke following TEVAR. Further evidence is needed to determine whether procedural modifications, including LSA revascularization, reduce the incidence of stroke associated with TEVAR

Migration of the Nellix Endoprosthesis

Background This study reports the incidence and sequelae of migration of the Nellix (Endologix Inc, Irvine, Calif) endoprosthesis after endovascular aneurysm sealing. Methods A review was performed of the follow-up imaging of all endovascular aneurysm sealing patients in a university hospital endovascular program who had a minimum follow-up of 1 year. The first postoperative and latest follow-up computed tomography scans were used to measure the distances between the proximal and distal borders of the stent grafts relative to reference vessels using a previously validated technique. Device migration was based on previously established criteria and defined as any stent graft movement of ≥4 mm related to a predefined reference vessel. Device movement in a caudal direction was given a positive value, and movement in a cranial direction was denoted by a negative value. Results Eighteen patients (35 stent grafts) were eligible for inclusion in this retrospective review. The mean preoperative abdominal aortic aneurysm diameter was 57 mm (standard deviation [SD], 5; range, 50-67 mm) and aortic neck length was 30 mm (SD, 16; range, 6-62 mm). Proximal migration, according to study definitions, was identified in six stent grafts (17%), all in a caudal direction. At 1 year the mean proximal migration distance was +6.6 mm (SD, 1.6; range, +4.7-+9.2 mm). Migration occurred in a single stent graft in four patients and bilaterally in one. No distal migration occurred. Conclusions Proximal migration of the Nellix endoprosthesis does occur and was without any sequelae in our series. Further investigations into the long-term positional stability of the Nellix device, together with a more thorough understanding of the etiology and consequences of migration, are required. Author conflict of interest: F.T. and R.F.K. have received professional fees and educational grants from Endologix. The editors and reviewers of this article have no relevant financial relationships to disclose per the JVS policy that requires reviewers to decline review of any manuscript for which they may have a conflict of interest

Hierarchical fibrillar scaffolds obtained by non-conventional layer-by-layer electrostatic self-assembly

A new approach of layer-by-layer assembling is disclosed, able to create nano/micro fibrils or nanocoatings inside 3D scaffolds using non-fibrils polyelectrolytes for tissue engineering applications. This approach shows to be promising for develop advanced scaffolds with controlled nano/micro environment, nature and architecture similar to natural extracellular matrix, with improved biological performance

Endovascular repair versus open surgery in patients with ruptured abdominal aortic aneurysms: Clinical outcomes with 1-year follow-up

ObjectiveTo compare the clinical outcomes of treatment after endovascular repair and open surgery in patients with ruptured infrarenal abdominal aortic aneurysms (AAAs), including 1-year follow-up.MethodsAll consecutive conscious patients with ruptured infrarenal AAAs who presented to our tertiary care teaching hospital between January 1, 2001, and December 31, 2005, were included in this study (n = 55). Twenty-six patients underwent endovascular repair, and 29 patients underwent open surgery. Patients who were hemodynamically too unstable to undergo a computed tomography angiography scan were excluded. Outcomes evaluated were intraoperative mortality, 30-day mortality, systemic complications, complications necessitating surgical intervention, and mortality and complications during 1-year follow-up. The statistical tests we used were the Student t test, χ2 test, Fisher exact test, and Mann-Whitney U test (two sided; α = .05).ResultsThirty-day mortality was 8 (31%) of 26 patients who underwent endovascular repair and 9 (31%) of 29 patients who underwent open surgery (P = .98). Systemic complications and complications necessitating surgical intervention during the initial hospital stay were similar in both treatment groups (8/26 [31%] and 5/26 [19%] for endovascular repair, respectively, and 9/29 [31%] and 8/29 [28%] for open surgery, respectively; P > .40). During 1-year follow-up, two patients initially treated with endovascular repair died as a result of non–aneurysm-related causes; no death occurred in the open surgery group. Complications during 1-year follow-up were 1 (5%) of 20 for endovascular repair and 4 (16%) of 25 for open surgery (P = .36).ConclusionsOn the basis of our study with a highly selected population, the mortality and complication rates after endovascular repair may be similar compared with those after open surgery in patients treated for ruptured infrarenal AAAs

Predicting aortic complications after endovascular aneurysm repair

Background Lifelong surveillance is standard after endovascular repair of abdominal aortic aneurysm (EVAR), but remains costly, heterogeneous and poorly calibrated. This study aimed to develop and validate a scoring system for aortic complications after EVAR, informing rationalized surveillance. Methods Patients undergoing EVAR at two centres were studied from 2004 to 2010. Preoperative morphology was quantified using three-dimensional computed tomography according to a validated protocol, by investigators blinded to outcomes. Proportional hazards modelling was used to identify factors predicting aortic complications at the first centre, and thereby derive a risk score. Sidak tests between risk quartiles dichotomized patients to low- or high-risk groups. Aortic complications were reported by Kaplan–Meier analysis and risk groups were compared by log rank test. External validation was by comparison of aortic complications between risk groups at the second centre. Results Some 761 patients, with a median age of 75 (interquartile range 70–80) years, underwent EVAR. Median follow-up was 36 (range 11–94) months. Physiological variables were not associated with aortic complications. A morphological risk score incorporating maximum aneurysm diameter (P < 0·001) and largest common iliac diameter (measured 10 mm from the internal iliac origin; P = 0·004) allocated 75 per cent of patients to a low-risk group, with excellent discrimination between 5-year rates of aortic complication in low- and high-risk groups at both centres (centre 1: 12 versus 31 per cent, P < 0·001; centre 2: 12 versus 45 per cent, P = 0·002). Conclusion The risk score uses commonly available morphological data to stratify the rate of complications after EVAR. The proposals for rationalized surveillance could provide clinical and economic benefits

Scouting Automated Ratings Analyzing Habits (SARAH): A Statistical Methodology for Scouting and Player Development

The project serves a two-fold purpose: to reduce the time that scouts and coaches spend trying to identify what players have foundational on-ice habits, and to streamline the process of evaluating the developmental progress of a players' habits. Essentially what we did was first look at the various national women's hockey teams and identify the set of "habits" a player regularly executes (i.e., edgework, catching the puck in the hip pocket, pass placement, etc). Combining the dataset of players' habits with a set of players' microstats (entries via pass/stickhandling, exits via stickhandling/pass, accurate/inaccurate passes, etc.), we developed a random forest classification model to accurately predict if a player possesses a certain habit based on their set of microstats. We also used random forest regression on our data to see how habits impacted each specific microstat. Combining this with an estimate of how frequently players used each habit, we created a Player Development Matrix for a player's habits based entirely on their microstats. To help coaches, scouts, and anyone else access & use these tools, we've also created an interactive visualization for these models using our training dataset of national women's hockey teams in the last Worlds and Olympics