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.
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.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Objectives Our objective was to assess the short- and long-term outcome for patients after carotid body tumor (CBT) resection and discuss the potential pitfalls of the treatment. Methods An analysis ...was undertaken of all patients who underwent CBT resection at Royal Brisbane and Women's Hospital and Greenslopes Private Hospital between 1982 and 2007. Primary tumor characteristics, surgical technique, and outcomes were recorded and analyzed. Results A total of 49 consecutive CBT resections (2 recurrent tumors) were carried out in 39 patients (26 women 56%) who were a mean age of 49 years (range, 17-75 years). A nontender neck mass was the presenting complaint in 85%, followed by screening in familial or contralateral tumors in 26%. Familial cases occurred in 11 patients (28%). There were no operative deaths. Complications occurred in 13 of the 49 operations (27%), predominantly temporary nerve palsies and were more likely to occur in tumors of large volume or in cases of removal of coexisting vagal tumors. Malignant disease was present in seven cases (15%). All patients have been followed-up postoperatively for a mean of 11 years (range, 2-26 years). Metachronous paragangliomas have been discovered in six patients, all with familial disease. Conclusions Early resection of carotid body tumors should be undertaken while still small to minimize the risk of neural injury, which increases with tumor size. In cases of bilateral CBT, we recommend that the smaller tumor be resected first, before the staged resection of the larger contralateral tumor. In familial or bilateral tumor cases, other synchronous and metachronous paragangliomas should be excluded. Mandatory lifelong follow-up is essential.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
IMPORTANCE: It is unclear whether counseling to promote walking reduces the risk of major adverse cardiovascular events (MACE) in people with peripheral artery disease (PAD). OBJECTIVE: To test ...whether a counseling intervention designed to increase walking reduced the risk of MACE in patients with PAD. DESIGN, SETTING, AND PARTICIPANTS: The BIP trial was a randomized clinical trial, with recruitment performed between January 2015 and July 2018 and follow-up concluded in August 2023. Participants with walking impairment due to PAD from vascular departments in the Australian cities of Brisbane, Sydney, and Townsville were randomly allocated 1:1 to the intervention or control group. Data were originally analyzed in March 2024. INTERVENTION: Four brief counseling sessions aimed to help patients with the challenges of increasing physical activity. MAIN OUTCOMES AND MEASURES: The primary outcome was the between-group difference in risk of MACE, which included myocardial infarction (MI), stroke, and cardiovascular death. The relationship between Intermittent Claudication Questionnaire (ICQ) scores, PAD Quality of Life (PADQOL) scores, and MACE was examined with Cox proportional hazard regression analyses. RESULTS: A total of 200 participants were included, with 102 allocated to the counseling intervention (51.0%) and 98 to the control group (49.0%).Participants were followed up for a mean (SD) duration of 3.5 (2.6) years. Median (IQR) participant age was 70 (63-76) years, and 56 of 200 participants (28.0%) were female. A total of 31 individuals had a MACE (composed of 19 MIs, 4 strokes, and 8 cardiovascular deaths). Participants allocated to the intervention were significantly less likely to have a MACE than participants in the control group (10 of 102 participants 9.8% vs 21 of 98 21.4%; hazard ratio HR, 0.43; 95% CI, 0.20-0.91; P = .03). Greater disease-specific quality of life (QOL) scores at 4 months (ICQ: HR per 1–percentage point increase, 0.97; 95% CI, 0.95-0.99; P < .001; PADQOL factor 3 symptoms and limitations in physical functioning: HR per 1-unit increase, 0.91; 95% CI, 0.84-0.98; P = .01) and at 12 months (ICQ: HR per 1–percentage point increase, 0.97; 95% CI, 0.95-0.99; P = .003; PADQOL factor 3: HR per 1-unit increase, 0.91; 95% CI, 0.84-0.98; P = .02) were associated with a lower risk of MACE. In analyses adjusted for ICQ or PADQOL factor 3 scores at either 4 or 12 months, allocation to the counseling intervention was no longer significantly associated with a lower risk of MACE. CONCLUSIONS AND RELEVANCE: This post hoc exploratory analysis of the BIP randomized clinical trial suggested that the brief counseling intervention designed to increase walking may reduce the risk of MACE, possibly due to improvement in QOL. TRIAL REGISTRATION: anzctr.org.au Identifier: ACTRN12614000592640
An extensive mechanistic investigation has been carried out on ethylene polymerizations catalyzed by neutral Ni(II) catalysts derived from bulky anilinotropone ligands. Complexes and precatalysts ...prepared include aryl derivatives (2,6-i-Pr2C6H3)NC7H4O(7-Aryl)Ni(Ph)(PPh3) (9, Aryl = phenyl(a), 1-naphthyl(b), p-methoxyphenyl(c), p-trifluoromethylphenyl(d)), alkyl derivatives (2,6- i Pr2C6H3)NC7H5ONi(R)(2,4-lutidine) (16, R = Et (a), n-Pr (b)) and (2,6- i Pr2C6H3)NC7H5ONi(R)(PPh3) (17, R = Et (a), n-Pr (b), n-hexyl (c), i-Pr (d)), and the nickel hydride complex (2,6- i Pr2C6H3)NC7H5ONi(H)(PPh3), 20. Branched polyethylenes are produced at 40−80 °C in toluene with M n values in the 100−200K range and molecular weight distributions of ca. 1.4−2.2. Branching ranges from 15 to 64 branches/1000 carbons depending on temperature and ethylene pressure. The electron-withdrawing −CF3 substituent on the 7-aryl group increases activity but has little effect on branching and molecular weight. NMR experiments establish that in the case of the PPh3-substituted systems, the catalyst rests as an equilibrating mixture of the alkyl phosphine and the alkyl ethylene complexes. At high ethylene pressures, the turnover frequency saturates, indicating that the equilibrium has shifted nearly completely to the alkyl olefin complex. Under these conditions, the barriers to migratory insertion were determined to be ca. 16−17 kcal/mol for 9a, 9c, 9d, and 16a. Extraction of 2,6-lutidine from complexes 16a,b yields highly dynamic β-agostic alkyl complexes (2,6-i-Pr2C6H3)NC7H5ONi(Et) 21 and (2,6-i-Pr2C6H3)NC7H5ONi(i-Pr) 22. Free energy barriers to nickel−carbon bond rotation and β-hydride elimination of 11.1 and ca. 17 kcal/mol, respectively, were determined for 22. Themolysis of 17c at 50 °C generates hydride 20 and hexene and occurs by two pathways, one independent of PPh3 and one retarded by PPh3. At much slower rates, hydride 20 reductively eliminates free ligand, which ultimately generates a bis-ligand complex, 25. Catalyst decay under polymerization conditions was shown to occur by a similar process to generate free ligand and a bis-ligand complex formed by reaction of free ligand with an active catalyst species. The major chain transfer route is a simple β-elimination process, not chain transfer to monomer.
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IJS, KILJ, NUK, PNG, UL, UM
Ankle-brachial pressure index (ABPI) is commonly measured in people referred to vascular specialists. This study aimed to assess the association of high ABPI (≥ 1.4) with cardiovascular events in ...people with peripheral artery disease (PAD). 1533 participants with PAD diagnosed by a vascular specialist were prospectively recruited from four out-patient clinics in Australia. ABPI was measured at recruitment and the occurrence of myocardial infarction (MI), stroke or cardiovascular death (major cardiovascular events; MACE) and any amputation were recorded over a median (inter-quartile range) follow-up of 3.3 (1.0-7.1) years. The association of high, compared to normal, low (0.5-0.9) or very low (<0.5), ABPI with clinical events was estimated using Cox proportional hazard analyses, adjusting for traditional risk factors and reported as hazard ratio with 95% confidence intervals. 596 (38.9%), 676 (44.1%), 157 (10.2%) and 104 (6.8%) participants had normal, low, very low and high ABPI, respectively. Participants with high ABPI had increased risk of MACE, MI and death by comparison to those with either normal ABPI 1.69 (1.07, 2.65), 1.93 (1.07, 3.46) and 1.67 (1.09, 2.56) or either low or very low ABPI 1.51 (1.02, 2.23), 1.92 (1.16, 3.19) and 1.47 (1.02, 2.14) after adjusting for other risk factors. Findings were similar in a sensitivity analysis excluding people with ABPI only measured in one leg (n = 120). Participants with high ABPI also had an increased risk of MACE and MI compared to those with very low ABPI alone. High ABPI is a strong indicator of excess risk of cardiovascular events amongst people with PAD.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The aims of this study were firstly to assess the correlation between disease specific measures of quality of life (QOL) and physical performance and activity, and secondly to identify demographic, ...clinical, functional, and physical activity measures independently associated with QOL in people with intermittent claudication.
This was a cross sectional observational study of 198 people with intermittent claudication caused by peripheral artery disease who were recruited prospectively. QOL was assessed with the intermittent claudication questionnaire (ICQ) and the eight-theme peripheral artery disease quality of life questionnaire. Physical performance was assessed with the six minute walk test (6MWT) and short physical performance battery (SPPB), and an accelerometer was used to measure seven day step count. The associations between QOL scores and 6MWT distance, SPPB scores and seven day step count were examined using Spearman Rho's (ρ) correlation and multivariable linear regression.
ICQ scores were significantly correlated with 6MWT distance (ρ = 0.472, p < .001), all four SPPB scores (balance ρ = 0.207, p = .003; gait speed ρ = 0.303, p < .001; chair stand ρ = 0.167, p = .018; total ρ = 0.265, p < .001), and seven day step count (ρ = 0.254, p < .001). PADQOL social relationships and interactions (ρ = 0.343, p < .001) and symptoms and limitations in physical functioning (ρ = 0.355, p < .001) themes were correlated with 6MWT distance. The 6MWT distance was independently positively associated with ICQ and both PADQOL theme scores (ICQ: B 0.069, p < .001; PADQOL social relationships and interactions: B 0.077, p < .001; PADQOL symptoms and limitations in physical functioning: B 0.069, p < .001).
Longer 6MWT distance independently predicted better physical and social aspects of QOL in people with intermittent claudication supporting its value as an outcome measure.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background The aim of this study was to assess the relationship between serum lipoprotein (a) (Lpa) concentration and the requirement for peripheral artery disease (PAD) operations or incidence of ...major adverse cardiovascular events. Methods and Results A total of 1472 people with PAD presenting with intermittent claudication (n=355), abdominal aortic aneurysm (n=989) or critical limb ischemia (n=128) were prospectively recruited from 4 outpatient clinics in Australia. Lp(a) was measured in serum samples collected at recruitment using an immunoassay. Participants were followed for a median (interquartile range) of 2.4 (0.1-6.1) years to record requirement for any PAD operation, defined to include any open or endovascular PAD intervention (lower limb peripheral revascularization, abdominal aortic aneurysm repair, other aneurysm repair, or carotid artery revascularization). Myocardial infarctions, strokes, and deaths were also recorded. The association of Lp(a) with events was assessed using Cox proportional hazard analysis adjusting for traditional risk factors. Participants with Lp(a) ≥30 mg/dL had a greater requirement for any PAD operation (hazard ratio, 1.20, 95% CI, 1.02-1.41) and lower limb peripheral revascularization alone (hazard ratio 1.33, 95% CI, 1.06-1.66) but no increased risk of major adverse cardiovascular events or all-cause mortality. Lp(a) ≥50 mg/dL and a 40 mg/dL increase in Lp(a) were also associated with an increased risk of lower limb peripheral revascularization alone but not with other outcomes. Conclusions In participants with PAD referred for hospital management those with high Lp(a) had greater requirement for lower limb peripheral revascularization but Lp(a) was not consistently associated with other clinical events.
Background There is no drug therapy for abdominal aortic aneurysm ( AAA ). FAME-2 (Fenofibrate in the Management of Abdominal Aortic Aneurysm 2) was a placebo-controlled randomized trial designed to ...assess whether administration of 145 mg of fenofibrate/d for 24 weeks favorably modified circulating markers of AAA. Methods and Results Patients with AAA s measuring 35 to 49 mm and no contraindication were randomized to fenofibrate or identical placebo. The primary outcome measures were the differences in serum osteopontin and kallistatin concentrations between groups. Secondary analyses compared changes in the circulating concentration of AAA -associated proteins, and AAA growth, between groups using multivariable linear mixed-effects modeling. A total of 140 patients were randomized to receive fenofibrate (n=70) or placebo (n=70). By the end of the study 3 (2.1%) patients were lost to follow-up and 18 (12.9%) patients had ceased trial medication. A total of 85% of randomized patients took ≥80% of allocated tablets and were deemed to have complied with the medication regimen. Patients' allocated fenofibrate had expected reductions in serum triglycerides and estimated glomerular filtration rate, and increases in serum homocysteine. No differences in serum osteopontin, kallistatin, or AAA growth were observed between groups. Conclusions Administering 145 mg/d of fenofibrate for 24 weeks did not significantly reduce serum concentrations of osteopontin and kallistatin concentrations, or rates of AAA growth in this trial. The findings do not support the likely benefit of fenofibrate as a treatment for patients with small AAA s. Clinical Trial Registration URL : www.anzctr.org.au . Unique identifier: ACTRN 12613001039774.
Experimental studies suggest that fenofibrate prevents abdominal aortic aneurysm (AAA) development by lowering aortic osteopontin (OPN) concentration and reducing the number of macrophages ...infiltrating the aortic wall. The current study examined the effects of a short course of fenofibrate on AAA pathology in people with large AAAs awaiting aortic repair.
This randomised double blind parallel trial included male and female participants aged ≥ 60 years who had an asymptomatic AAA measuring ≥ 50 mm and were scheduled to undergo open AAA repair. Participants were allocated to fenofibrate (145 mg/day) or matching placebo for at least two weeks before elective AAA repair. Blood samples were collected at recruitment and immediately prior to surgery. AAA biopsies were obtained during aortic surgery. The primary outcomes were (1) AAA OPN concentration; (2) serum OPN concentration; and (3) number of AAA macrophages. Exploratory outcomes included circulating and aortic concentrations of other proteins previously associated with AAA. Outcomes assessed at a single time point were compared using logistic regression. Longitudinal outcomes were compared using linear mixed effects models.
Forty-three participants were randomised. After three withdrawals, 40 were followed until the time of surgery (21 allocated fenofibrate and 19 allocated placebo). As expected, serum triglycerides reduced significantly from recruitment to the time of surgery in participants allocated fenofibrate. No differences in any of the primary and exploratory outcomes were observed between groups.
A short course of 145 mg of fenofibrate/day did not lower concentrations of OPN or aortic macrophage density in people with large AAAs.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background This study was undertaken to document the results of our current practice of open mesenteric revascularization to enable comparison with the recent trend of percutaneous endovascular ...therapy for the treatment of chronic mesenteric ischemia. Methods Patients were identified via operation code data as well ongoing audit data from 1992 until 2006. Only patients with a history of chronic mesenteric ischemia secondary to atherosclerosis for 3 months or longer were included in the study. Follow-up data have been collected prospectively and include clinical examination and history, as well as graft surveillance consisting of mesenteric duplex ultrasonography, computed tomography, and/or angiography every 6 months for 3 years and then yearly thereafter. Results Thirty-nine consecutive patients underwent 41 open revascularization procedures for chronic mesenteric ischemia, comprising 67 bypass grafts. The mean patient age was 65 years (range, 45-85 years), and 44% (n = 17) were male. Symptoms were present on average for 11 months (range, 4-48 months) before treatment. The average weight loss was 11.4 kg, and three patients (7.6%) also had evidence of ischemic enteritis. There was one perioperative death, thus giving a perioperative mortality rate of 2.5%. Perioperative morbidity occurred in five patients (12.2%). Primary graft patency was 92% at 5 years. Seven patients died during follow-up, which ranged from 4 to 161 months (mean, 39 months)—one (2.5%) from mesenteric ischemia. Two (5%) other patients have had recurrent mesenteric ischemic symptoms. Conclusions Open surgical mesenteric revascularization by bypass grafting for atherosclerotic-induced chronic mesenteric ischemia can be performed with low mortality and morbidity and provides excellent long-term primary patency rates and symptom-free outcomes. Pending more data on the acute and long-term results of endovascular techniques, open mesenteric revascularization remains the gold standard for most patients with chronic mesenteric ischemia.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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