RESUMO
Lack of long-term patency has hindered the clinical use of small-diameter prosthetic vascular grafts with the majority of these failures due to the development of neointimal hyperplasia. Previous studies by our laboratory revealed that small-diameter expanded polytetrafluoroethylene (ePTFE) grafts coated with antioxidant elastomers are a promising localized therapy to inhibit neointimal hyperplasia. This work is focused on the development of poly(diol-co-citrate-co-ascorbate) (POCA) elastomers with tunable properties for coating ePTFE vascular grafts. A bioactive POCA elastomer (@20 : 20 : 8, [citrate] : [diol] : [ascorbate]) coating was applied on a 1.5 mm diameter ePTFE vascular graft as the most promising therapeutic candidate for reducing neointimal hyperplasia. Surface ascorbate density on the POCA elastomer was increased to 67.5 ± 7.3 ng mg-1 cm-2. The mechanical, antioxidant, biodegradable, and biocompatible properties of POCA demonstrated desirable performance for in vivo use, inhibiting human aortic smooth muscle cell proliferation, while supporting human aortic endothelial cells. POCA elastomer coating number was adjusted by a modified spin-coating method to prepare small-diameter ePTFE vascular grafts similar to natural vessels. A significant reduction in neointimal hyperplasia was observed after implanting POCA-coated ePTFE vascular grafts in a guinea pig aortic interposition bypass graft model. POCA elastomer thus offers a new avenue that shows promise for use in vascular engineering to improve long-term patency rates by coating small-diameter ePTFE vascular grafts.
Assuntos
Elastômeros , Politetrafluoretileno , Animais , Prótese Vascular , Citratos , Ácido Cítrico , Células Endoteliais/patologia , Cobaias , Hiperplasia/prevenção & controleRESUMO
BACKGROUND: Federal initiatives have recently addressed the sex bias that exists in biomedical and clinical research. However, improvement to the inclusion of sex as a biological variable remains unknown. METHODS: We performed a 5-year follow-up study of all clinical and biomedical research articles published in 5 surgical journals from January 1, 2017, through December 31, 2018. Human, animal, and cell subjects were analyzed for study/subject type, sex of participants, sex matching, and sex-based data reporting, analysis, and discussion. RESULTS: Comparing 2017 to 2018 with 2011 to 2012, slightly more articles reported the sex of the human studied (87% vs 83%; P = .001). Inclusion of both sexes remained high (94% vs 95%; P = .22), but sex-based data reporting (36% vs 38%; P = .17), analysis (35% vs 33%; P = .39), and discussion of results (10% vs 23%; P < .0001) remained unchanged or worsened. Regarding animal research, the number of articles that stated the sex studied remained unchanged (79% vs 78%; P = .67); if stated, slightly more included both sexes (7% vs 3%; P = .002). Regarding cell research, fewer articles reported the sex of the cells studied (5% vs 24%; P = .0001); if stated, more articles included both sexes, but the difference did not reach statistical significance (25% vs 7%; P = .34). Sex matching remained poor with only 50% of human, 4% of animal, and 9% of cell studies matching the inclusion of both sexes by at least 50%. CONCLUSION: Sex bias persists in surgical research. The majority of articles failed to report, analyze, or discuss results based on sex, which will negatively affect clinical translatability and outcomes of evidence-based medicine.
Assuntos
Bibliometria , Pesquisa Biomédica , Cirurgia Geral , Sexismo/estatística & dados numéricos , Animais , Feminino , Seguimentos , Humanos , Masculino , Fatores de TempoRESUMO
Importance: Although fluoroquinolones are commonly prescribed antibiotics in the US, recent international studies have shown an increased risk of aortic aneurysm and dissection after fluoroquinolone use, leading to US Food and Drug Administration warnings limiting use for high-risk patients. It is unclear whether these data are true for the US population and who is truly high risk. Objective: To assess aortic aneurysm and dissection risks in a heterogeneous US population after fluoroquinolone use. Design, Setting, and Participants: Prescription fills for fluoroquinolones or a comparator antibiotic from 2005 to 2017 among commercially insured individuals aged 18 to 64 years were identified in this retrospective analysis of MarketScan health insurance claims. This cohort study included 27â¯827â¯254 US adults (47â¯596â¯545 antibiotic episodes), aged 18 to 64 years, with no known previous aortic aneurysm or dissection, no recent antibiotic exposure, and no recent hospitalization. Exposures: Outpatient fill of an oral fluoroquinolone or comparator antibiotic (amoxicillin-clavulanate, azithromycin, cephalexin, clindamycin, and sulfamethoxazole-trimethoprim). Main Outcomes and Measures: The 90-day incidence of aortic aneurysm and dissection. Inverse probability of treatment weighting in Cox regression was used to estimate the association between fluoroquinolone fill and 90-day aneurysm incidence. Interaction terms were used to assess the association of known risk factors (ie, sex, age, and comorbidities) with aneurysm after fluoroquinolone use. Data analysis was performed March 2019 to May 2020. Results: Of 47â¯596â¯545 prescription fills, 9â¯053â¯961 (19%) were fluoroquinolones and 38â¯542â¯584 (81%) were comparator antibiotics. The median (interquartile range) age of adults with fluoroquinolone fills was 47 (36-57) years vs 43 (31-54) years with comparator antibiotic fills. Women comprised 61.3% of fluoroquinolone fills and 59.5% of comparator antibiotic fills. Before weighting, the 90-day incidence of newly diagnosed aneurysm was 7.5 cases per 10â¯000 fills (6752 of 9â¯053â¯961) after fluoroquinolones compared with 4.6 cases per 10â¯000 fills (17â¯627 of 38â¯542â¯584) after comparator antibiotics. After weighting for demographic characteristics and comorbidities, fluoroquinolone fills were associated with increased incidence of aneurysm formation (hazard ratio [HR], 1.20; 95% CI, 1.17-1.24). More specifically, compared with comparator antibiotics, fluoroquinolone fills were associated with increased 90-day incidence of abdominal aortic aneurysm (HR, 1.31; 95% CI, 1.25-1.37), iliac artery aneurysm (HR, 1.60; 95% CI, 1.33-1.91), and other abdominal aneurysm (HR, 1.58; 95% CI, 1.39-1.79), and adults were more likely to undergo aneurysm repair (HR, 1.88; 95% CI, 1.44-2.46). When stratified by age, all adults 35 years or older appeared at increased risk (18-34 years: HR, 0.99 [95% CI, 0.83-1.18]; 35-49 years: HR, 1.18 [95% CI, 1.09-1.28]; 50-64 years: HR, 1.24 [95% CI, 1.19-1.28]; P = .04). Conclusions and Relevance: This study found that fluoroquinolones were associated with increased incidence of aortic aneurysm formation in US adults. This association was consistent across adults aged 35 years or older, sex, and comorbidities, suggesting fluoroquinolone use should be pursued with caution in all adults, not just in high-risk individuals.