Highly compliant biomimetic scaffolds for small diameter tissue-engineered vascular grafts (TEVGs) produced via melt electrowriting (MEW).

Biofabrication approaches toward the development of tissue-engineered vascular grafts (TEVGs) have been widely investigated. However, successful translation has been limited to large diameter applications, with small diameter grafts frequently failing due to poor mechanical performance, in particular mismatched radial compliance. Herein, melt electrowriting (MEW) of poly(ϵ-caprolactone) has enabled the manufacture of highly porous, biocompatible microfibre scaffolds with physiological anisotropic mechanical properties, as substrates for the biofabrication of small diameter TEVGs. Highly reproducible scaffolds with internal diameter of 4.0 mm were designed with 500 and 250µm pore sizes, demonstrating minimal deviation of less than 4% from the intended architecture, with consistent fibre diameter of 15 ± 2µm across groups. Scaffolds were designed with straight or sinusoidal circumferential microfibre architecture respectively, to investigate the influence of biomimetic fibre straightening on radial compliance. The results demonstrate that scaffolds with wave-like circumferential microfibre laydown patterns mimicking the architectural arrangement of collagen fibres in arteries, exhibit physiological compliance (12.9 ± 0.6% per 100 mmHg), while equivalent control geometries with straight fibres exhibit significantly reduced compliance (5.5 ± 0.1% per 100 mmHg). Further mechanical characterisation revealed the sinusoidal scaffolds designed with 250µm pores exhibited physiologically relevant burst pressures of 1078 ± 236 mmHg, compared to 631 ± 105 mmHg for corresponding 500µm controls. Similar trends were observed for strength and failure, indicating enhanced mechanical performance of scaffolds with reduced pore spacing. Preliminaryin vitroculture of human mesenchymal stem cells validated the MEW scaffolds as suitable substrates for cellular growth and proliferation, with high cell viability (>90%) and coverage (>85%), with subsequent seeding of vascular endothelial cells indicating successful attachment and preliminary endothelialisation of tissue-cultured constructs. These findings support further investigation into long-term tissue culture methodologies for enhanced production of vascular extracellular matrix components, toward the development of the next generation of small diameter TEVGs.

Quality assurance in 3D-printing: A dimensional accuracy study of patient-specific 3D-printed vascular anatomical models.

3D printing enables the rapid manufacture of patient-specific anatomical models that substantially improve patient consultation and offer unprecedented opportunities for surgical planning and training. However, the multistep preparation process may inadvertently lead to inaccurate anatomical representations which may impact clinical decision making detrimentally. Here, we investigated the dimensional accuracy of patient-specific vascular anatomical models manufactured via digital anatomical segmentation and Fused-Deposition Modelling (FDM), Stereolithography (SLA), Selective Laser Sintering (SLS), and PolyJet 3D printing, respectively. All printing modalities reliably produced hand-held patient-specific models of high quality. Quantitative assessment revealed an overall dimensional error of 0.20 ± 3.23%, 0.53 ± 3.16%, -0.11 ± 2.81% and -0.72 ± 2.72% for FDM, SLA, PolyJet and SLS printed models, respectively, compared to unmodified Computed Tomography Angiograms (CTAs) data. Comparison of digital 3D models to CTA data revealed an average relative dimensional error of -0.83 ± 2.13% resulting from digital anatomical segmentation and processing. Therefore, dimensional error resulting from the print modality alone were 0.76 ± 2.88%, + 0.90 ± 2.26%, + 1.62 ± 2.20% and +0.88 ± 1.97%, for FDM, SLA, PolyJet and SLS printed models, respectively. Impact on absolute measurements of feature size were minimal and assessment of relative error showed a propensity for models to be marginally underestimated. This study revealed a high level of dimensional accuracy of 3D-printed patient-specific vascular anatomical models, suggesting they meet the requirements to be used as medical devices for clinical applications.

Biofabrication of small diameter tissue-engineered vascular grafts.

Current clinical treatment strategies for the bypassing of small diameter (<6 mm) blood vessels in the management of cardiovascular disease frequently fail due to a lack of suitable autologous grafts, as well as infection, thrombosis, and intimal hyperplasia associated with synthetic grafts. The rapid advancement of 3D printing and regenerative medicine technologies enabling the manufacture of biological, tissue-engineered vascular grafts (TEVGs) with the ability to integrate, remodel, and repair in vivo, promises a paradigm shift in cardiovascular disease management. This review comprehensively covers current state-of-the-art biofabrication technologies for the development of biomimetic TEVGs. Various scaffold based additive manufacturing methods used in vascular tissue engineering, including 3D printing, bioprinting, electrospinning and melt electrowriting, are discussed and assessed against the biomechanical and functional requirements of human vasculature, while the efficacy of decellularization protocols currently applied to engineered and native vessels are evaluated. Further, we provide interdisciplinary insight into the outlook of regenerative medicine for the development of vascular grafts, exploring key considerations and perspectives for the successful clinical integration of evolving technologies. It is expected that continued advancements in microscale additive manufacturing, biofabrication, tissue engineering and decellularization will culminate in the development of clinically viable, off-the-shelf TEVGs for small diameter applications in the near future. STATEMENT OF SIGNIFICANCE: Current clinical strategies for the management of cardiovascular disease using small diameter vessel bypassing procedures are inadequate, with up to 75% of synthetic grafts failing within 3 years of implantation. It is this critically important clinical problem that researchers in the field of vascular tissue engineering and regenerative medicine aim to alleviate using biofabrication methods combining additive manufacturing, biomaterials science and advanced cellular biology. While many approaches facilitate the development of bioengineered constructs which mimic the structure and function of native blood vessels, several challenges must still be overcome for clinical translation of the next generation of tissue-engineered vascular grafts.

Symptomatic infrarenal aortic aneurysm sac expansion 5 years post-endovascular repair without an identifiable endoleak.

A 71-year-old male presented with a symptomatic expanding 11 cm infrarenal aortic aneurysm 5 years post-endovascular aortic repair. Duplex ultrasound and angiography showed no identifiable endoleak but confirmed an enlarging aneurysm sac with a new saccular configuration. The ultrasound findings were particularly unusual in that the aneurysm sac was a mixture of hardened echogenic material and an anechoic fluid-like substance, with the echogenic material appearing to float around the sac with gravitational dependence. Open surgical intervention was performed. The aneurysm appeared pressurised with forceful expulsion of the sac contents post-incision, though again no endoleak was identified. The sac contents were confirmed as a mixture of clear fluid and hardened haematoma. At 6 weeks follow-up there was complete return of the aneurysm sac almost to its pre-open surgery state. Multiple endoleak theories were considered from initial imaging through to follow-up.

Medical Graduates, Tertiary Hospitals, and Burnout: A Longitudinal Cohort Study.

BACKGROUND: Burnout among junior doctors can affect patient care. We conducted a longitudinal cohort study designed to explore the incidence of burnout in medical interns and to examine the changes in burnout during the course of the intern year. METHODS: Interns were recruited at two tertiary hospitals in Brisbane, Australia (n=180). Participants completed surveys at four time points during their internship year. All interns (100%) completed the baseline survey during their orientation. Response rates were 85%, 88%, and 79%, respectively, at 5-week, 6-month, and 12-month follow-up. RESULTS: Interns reported high levels of personal and work-related burnout throughout the year that peaked at 6 months with mean scores of 42.53 and 41.81, respectively. Increases of 5.1 points (confidence interval [CI] 2.5,7.7; P=0.0001) and 3.5 points (CI 1.3,5.6; P=0.0015) were seen at 6 months for personal and work-related burnout, respectively. The mean score for patient-related burnout at 12 months was 25.57, and this number had increased significantly by 5.8 points (CI 3.2,8.5; P<0.0001) throughout the year. Correlation with demographic variables (age, sex) were found. The total incidence of burnout was 55.9%. CONCLUSION: Our study showed that burnout is a common problem among interns. The high incidence of burnout demonstrates the need for appropriate strategies to prevent adverse effects on doctors' quality of life and on the quality of care patients receive.

Return to work after coronary artery bypass in patients aged under 50 years.

BACKGROUND: This study was designed to identify factors associated with return to work and quality of life in patients undergoing primary coronary artery bypass at age <50 years. METHODS: 172 patients<50-years old underwent primary coronary artery bypass between January 2000 and December 2006. Predictors of return to work were analysed from variables in a prospectively collected database and on follow-up by the SF-36 questionnaire in 129 (75%) patients. RESULTS: 136 (79%) patients were working prior to surgery. The educational level was: primary 14.5%, secondary 47%, trade 22%, tertiary 13%, and postgraduate 3%. Type of occupation was blue collar 51%, white collar 41%, pensioner 27%, and unspecfied 8%. The mean follow-up was 86.4±23.4 months. One hundred and twenty-six (69%) patients attended cardiac rehabilitation. Forty (23%) patients experienced recurrence of symptoms; 11 (6%) required reintervention. One hundred and twenty-seven (93%) patients returned to work postoperatively. Univariate predictors of return to work were male sex, blue-collar work, and working prior to surgery. Independent predictors of return to work were working prior to surgery and blue-collar work. Patients who returned to work had significantly higher scores in all 8 domains on the SF36-Questionnaire compared to those who did not return to work. CONCLUSIONS: Preoperative employment and blue collar occupation were associated with a higher rate of return to work after coronary artery bypass in patients of working age. Patients who returned to work had significantly better measured quality of life than those who did not.

Treatment outcomes for ischemic heart disease in dialysis-dependent patients.

OBJECTIVE: To compare outcomes following intervention in dialysis-dependent patients with ischemic heart disease. BACKGROUND: Ischemic heart disease is a major cause of mortality in dialysis-dependent patients. Coronary revascularization and medical modification to relieve symptoms is common, however, there is no clear consensus regarding optimal treatment. METHOD: Ninety dialysis-dependent patients with ischemic heart disease were prospectively assessed between 1999 and 2009, with a median follow-up of 24 months; 35 received best medical management, 31 had percutaneous coronary angioplasty and stenting, and 24 had coronary artery bypass grafting. RESULTS: By multivariate analysis, higher body mass index and lower logistic EuroSCORE were associated with having either procedure compared to medical management. Using the time-to-event Kaplan-Meier method, both stenting and coronary bypass grafting had lower risks of an adverse outcome than best medical management. Mortality was 40/90 (44.4%). Multivariate predictors of mortality were smoking and a logistic EuroSCORE of 7-14. Overall mortality was not different among groups, however, the stent group had a survival advantage at 30-days and 1-year compared to the coronary bypass group. Composite median survival was 52.3 months. SF-36 questionnaires showed quality of life after bypass grafting was significantly better than medical management or stenting. Physical function was better after bypass grafting compared to medical management or stenting. CONCLUSION: Dialysis-dependent patients with ischemic heart disease have poor survival despite intervention. Coronary artery bypass achieves fewer composite adverse events and better quality of life than stenting. Symptoms and coronary anatomy should dictate treatment decisions in dialysis-dependent patients.

Primary coronary artery bypass surgery in the presence of decreasing preoperative renal function: effect on short-term outcomes.

BACKGROUND: This study evaluated the impact of decreasing renal function on short-term outcomes in patients undergoing primary coronary artery bypass grafting (CABG). METHODS: The study period was from February 1999 to February 2009. Data on 4050 patients undergoing primary CABG were prospectively collected and analyzed retrospectively. The study population was divided into 3 groups: the CABG:N group, patients with preoperative serum creatinine levels <2 mg/dL (n = 3947); the CABG:RF group, patients with preoperative creatinine levels >2 mg/dL (n = 87); and the CABG:D group, patients on dialysis (n = 16). RESULTS: The significant differences between the groups (CABG:D > CABG:RF > CABG:N) in short-term outcomes were with respect to blood product use (P < .001), postoperative acute myocardial infarction (P < .001), pulmonary complications (P .001), infection (P < .001), and death (P < .001). The risk of short-term death (30 days) in the CABG:D group (4/16, 25%) was 25 times greater than that in the CABG:N group (38/3947, 0.96%). CONCLUSION: CABG in the presence of renal failure is associated with significant morbidity and mortality.

Ischemic cardiomyopathy: midterm survival and its predictors.

BACKGROUND: the aim of the study was to analyze all-cause mortality and predictors of long-term survival after myocardial revascularization for ischemic cardiomyopathy. METHOD: data of 101 patients (mean age, 63.86 years; age range, 30-85 years; 92% male), operated on with stable coronary artery disease and left ventricular ejection fraction <30% between April 2000 and June 2010, were analyzed. RESULTS: operative mortality was 1.9% (2/101). There was a significant improvement in left ventricular ejection fraction from 25.99% ± 3.8% preoperatively to 34% ± 12% postoperatively (p <0.0001). The mean duration of follow-up was 56.3 ± 33 months, and it was 97% complete (98/101). There were 18/96 (18.75%) late deaths. Overall actuarial survival at 1, 3, 5, and 10 years was 96%, 89%, 83% and 75%, respectively. Univariate predictors of late death were preoperative arrhythmia, cerebrovascular disease, peripheral vascular disease, and logistic EuroSCORE. Multivariate predictors of late death were cerebrovascular disease and preoperative arrhythmia. CONCLUSION: our study suggests that myocardial revascularization for ischemic cardiomyopathy improves left ventricular ejection fraction and is associated with favorable long-term survival. Patients with cerebrovascular disease and preoperative arrhythmias had poorer outcomes.

Surgical management and mid-term outcomes of 108 patients with infective endocarditis.

This study evaluates the early and mid-term outcomes, predictors of mortality and morbidity and quality of life of patients operated for infective endocarditis. Data on 108 patients undergoing 113 surgical procedures during October 1998 to January 2010 was prospectively collected. NYHA Class was >III in 49 (43.4%) cases. Thirty-seven (33%) patients had isolated mitral valve procedures, 58 (51%) had aortic valve, two had tricuspid valve and 16 had multivalvular procedures. Active endocarditis was noted in 86 (76%) procedures, native valve endocarditis in 105 (93%) and prosthetic valve endocarditis in eight procedures. Logistic EuroSCORE at presentation was >14 in 18 (17%) patients. Staphylococcus aureus was the most common organism isolated. Follow-up was carried out in 76/85 (88.37%) of surviving patients, and the mean follow-up time was 37.2 months. Functional class and quality of life (using EQ-5D Health Questionnaire) were assessed by telephone interviews. NYHA Class on follow-up was I-II in 62/76 (83%). Multivariate predictor of 30-day mortality was peripheral vascular disease (p = 0.025) whilst multivariate predictors of long-term survival were male sex (p = 0.01), peripheral vascular disease (p = 0.02) and bypass time (p = 0.006). The overall survival was 87% at one year and 80% at five years. Thirty-three percent (25/76) patients reported a score reflecting full health. Optimal antibiotic therapy and timely surgical intervention were associated with improved functional class, quality of life and mid-term survival.

Presentation with pulsatile xiphisternal bruise-Survival with a chronic ventricular rupture.

Ventricular free wall rupture is an acute, severe complication of myocardial infarction (MI). Accounting for 20-30% of MI mortality, ventricular rupture is fatal if not detected early and repaired surgically. The unique case of a delayed, chronic rupture is reported in a 64 year-old male who presented with a painless, pulsatile, sub-xiphisternal bruise, five years post MI. Trans-thoracic echocardiography (TTE) revealed haematoma extending posteriorly with only contrast echocardiography revealing an active communication between the sub-dermal area and the heart. Urgent surgery and a prolonged period in ICU enabled sufficient enough recovery for discharge.

Cardiac surgery in the presence of dialysis: effect on mid-term outcomes and quality of life.

BACKGROUND: this study evaluates the impact on short and mid-term outcomes and quality of life of dialysis dependent patients undergoing cardiac surgery. The benefit to patients from a bio-psycho-social perspective is put into context via an inter-personal patient interview. METHODS: the study period was from February 1999 to February 2009. Data on 45 dialysis dependent patients undergoing cardiac surgery was prospectively collected and analysed retrospectively. The mean age was 59.9 years and sex ratio (M:F) of 32:13. All patients were New York Heart Association (NYHA) class >2 preoperatively. Fifty-five percent (25/45) of these patients had coronary artery bypass graft surgery (CABG) and 28% (12/45) aortic valve replacement surgery alone. Forty-two variables were studied to define predictors of outcome. Follow-up was 100% (18/18) with a mean follow-up time of 48.1 months (0-124 months). They were followed up with quality of life and functional coping score surveys (SF-36). RESULTS: the main postoperative morbidities were pulmonary complications 20% (9/45), multi-organ failure 11% (5/45) and blood transfusion rates 40% (18/45). The 30 day mortality of the dialysis patients was 13.3% (6/45) and late death was 54% (21/39). Increasing age, pulmonary complications and blood product usage were the significant predictors of both 30 day mortality (age: p=0.02, pulmonary: p=0.003, blood product usage: p=0.03) and late death (age: p=0.008, pulmonary: p=0.02, blood product usage: p=0.02). New York Heart Association class was I-II in 83% (15/18) on long term follow up. All five patients awaiting renal transplants received their transplant in the first six months post-operatively. The overall survival at one year was 78% and five years was 40%. On SF-36 health questionnaire all patients scored less on physical functioning than the Australian norms (24.89 ± 4.10). CONCLUSIONS: cardiac surgery in the presence of renal failure is associated with significant morbidity and mortality. The overall survival and quality of life of dialysis patients undergoing cardiac surgery is poor.

Contemporary results following surgical repair of acute type a aortic dissection (AAAD): a single centre experience.

OBJECTIVES: The study aims to define predictors of neurological dysfunction, 30-day mortality, long-term survival and quality of life following repair of acute type A aortic dissection (AAAD). METHODS: Between 2000 and 2008, 65 patients underwent repair of AAAD. Sixty-four pre-, intra- and post-operative variables were studied. Mean follow-up was 26.6 months. RESULTS: The mean age was 61years; 60% were male and five had Marfan's syndrome. At presentation, ischaemic ECG changes were seen in 45%, malperfusion syndrome in 59%, moderate-severe aortic regurgitation in 48% and tamponade in 16%. EF was <40% in 17%. There was a delay of >12hours between diagnosis and operation in 64%. Axillary cannulation was performed in 37%. Cerebral protection was by hypothermic arrest (HCA) alone (19%), HCA with retrograde cerebral perfusion (RCP) (11%), or HCA with antegrade cerebral perfusion (ACP) (46%). The procedure was performed on cross-clamp in 24%. Full arch replacement was performed in 14% and concomitant coronary artery grafting was performed in 11%. Post-operative neurological dysfunction was present in 33.8%. The only significant predictor of poor neurological outcome was full arch replacement (p=0.04) on univariate analysis. In-hospital OR 30 mortality was 23.53%. Significant predictors of mortality were low ejection fraction (p=0.017) and post-operative renal failure (p=0.012). Long-term survival was 70% at two years, 50% at five years and 25% at nine years. Functional outcomes and long-term quality of life were assessed in 69% of patients who were alive at last follow-up. Ninety percent of patients reported minimal limitation on functional scores. Quality of life was assessed using the EQ-5D questionnaire. Forty-eight percent of patients recorded full health with an overall mean index of 0.854 (where the best possible score is 1) using the US preference weighted index score. CONCLUSIONS: Discharged patients have reasonable long-term survival and good quality of life.

Conjunctival and episcleral Splendore-Hoeppli phenomenon.

The Splendore-Hoeppli phenomenon originally described in 1908 is a rare pathological state with an as yet unknown cause. Reported is the Splendore-Hoeppli phenomenon present in both eyes of a 36-year-old woman. The pathology then proceeded to resolve itself completely within 10 weeks. Of note was the fact that the patient actually developed these granulomata despite being on high doses of oral steroids with the lesions disappearing despite her steroids being withdrawn during the resolution phase. An indication is that the phenomenon is unlikely to be because of an autoimmune response.