Abstract Objective: To determine the effects of “prolonged” antiplatelet therapy (that is, given for one month or more) on “vascular events” (non-fatal myocardial infarctions, non-fatal strokes, or vascular deaths) in various categories of patients. Design: Overviews of 145 randomised trials of “prolonged” antiplatelet therapy versus control and 29 randomised comparisons between such antiplatelet regimens. Setting: Randomised trials that could have been available by March 1990. Subjects: Trials of antiplatelet therapy versus control included about 70 000 “high risk” patients (that is, with some vascular disease or other condition implying an increased risk of occlusive vascular disease) and 30 000 “low risk” subjects from the general population. Direct comparisons of different antiplatelet regimens involved about 10 000 high risk patients. Results: In each of four main high risk categories of patients antiplatelet therapy was definitely protective. The percentages of patients suffering a vascular event among those allocated antiplatelet therapy versus appropriately adjusted control percentages (and mean scheduled treatment durations and net absolute benefits) were: (a) among about 20 000 patients with acute myocardial infarction, 10% antiplatelet therapy v 14% control (one month benefit about 40 vascular events avoided per 1000 patients treated (2P< 0.00001)); (b) among about 20 000 patients with a past history of myocardial infarction, 13% antiplatelet therapy v 17% control (two year benefit about 40/1000 (2P<0.00001)); (c) among about 10 000 patients with a past history of stroke or transient ischaemic attack, 18% antiplatelet therapy v 22% control (three year benefit about 40/1000 (2P<0.00001)); (d) among about 20 000 patients with some other relevant medical history (unstable angina, stable angina, vascular surgery, angioplasty, atrial fibrillation, valvular disease, peripheral vascular disease, etc), 9% v 14% in 4000 patients with unstable angina (six month benefit about 50/1000 (2P<0.00001)) and 6% v 8% in 16 000 other high risk patients (one year benefit about 20/1000 (2P<0.00001)). Reductions in vascular events were about one quarter in each of these four main categories and were separately statistically significant in middle age and old age, in men and women, in hypertensive and normotensive patients, and in diabetic and non: diabetic patients. Taking all high risk patients together showed reductions of about one third in non-fatal myocardial infarction, about one third in non-fatal stroke, and about one sixth in vascular death (each 2P<0.00001). There was no evidence that non-vascular deaths were increased, so in each of the four main high risk categories overall mortality was significantly reduced. The most widely tested antiplatelet regimen was “medium dose” (75-325 mg/day) aspirin. Doses throughout this range seemed similarly effective (although in an acute emergency it might be prudent to use an initial dose of 160-325 mg rather than about 75 mg). There was no appreciable evidence that either a higher aspirin dose or any other antiplatelet regimen was more effective than medium dose aspirin in preventing vascular events. The optimal duration of treatment for patients with a past history of myocardial infarction, stroke, or transient ischaemic attack could not be determined directly because most trials lasted only one, two, or three years (average about two years). Nevertheless, there was significant (2P<0.00001) further benefit between the end of year 1 and the end of year 3, suggesting that longer treatment might well be more effective. Among low risk recipients of “primary prevention” a significant reduction of one third in non: fatal myocardial infarction was, however, accompanied by a non-significant increase in stroke. Furthermore, the absolute reduction in vascular events was much smaller than for high risk patients despite a much longer treatment period (4.4% antiplatelet therapy v 4.8% control; five year benefit only about four per 1000 patients treated) and was not significant (2P=0.09). Conclusions: Among a much wider range of patients at high risk of occlusive vascular disease than is currently treated routinely, some years of antiplatelet therapy - with aspirin 75-325 mg/day or some other antiplatelet regimen (provided there are no contraindications) - offers worthwhile protection against myocardial infarction, stroke, and death. Significant benefit is evident not only among patients with unstable angina, suspected acute myocardial infarction, or a past history of myocardial infarction, stroke, or transient ischaemic attack, but also among many other categories of high risk patients (such as those having vascular procedures and those with stable angina or peripheral vascular disease). There is as yet, however, no clear evidence on the balance of risks and benefits of antiplatelet therapy in primary prevention among low risk subjects.

Collaborative overview of randomized trials of antiplatelet therapy .1. prevention of death, myocardial-infarction, and stroke by prolonged antiplatelet therapy in various categories of patients

Patients With Peripheral Arterial Disease (Lower Extremity, Renal, Mesenteric, and Abdominal Aortic) A Collaborative Report from the American Association for Vascular Surgery/Society for Vascular Surgery,* Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease) Endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation

/pdf/acc-aha-2005-practice-guidelines-for-the-management-of-4ltfid6e9i.pdf

ACC/AHA 2005 Practice Guidelines for the Management of Patients With Peripheral Arterial Disease (Lower Extremity, Renal, Mesenteric, and Abdominal Aortic)

Recommended standards for reports dealing with lower extremity ischemia: Revised version

Anesthesiology. First of two parts.

Diagnostic performance of 64-multidetector row coronary computed tomographic angiography for evaluation of coronary artery stenosis in individuals without known coronary artery disease: results from the prospective multicenter ACCURACY (Assessment by Coronary Computed Tomographic Angiography of Individuals Undergoing Invasive Coronary Angiography) trial.

[Preservation of normal metabolism in isolated canine thyroid by pulsatile perfusion: preliminary study].

Background: One of the most serious complications from plastic surgery is a thromboembolic event. The incidence of thromboembolism in truncal contouring procedures ranges from 1-9%. However, little physiologic evidence exists to support the observed hypercoagulable state. This is the first study to assess physiological markers of hypercoagulability, and one of few prospective studies addressing thromboembolic risk and prophylaxis in body contouring patients.

Abdominal Contouring Procedures Are Associated with a Physiologic Hypercoagulable State

INTRODUCTION: Already common in medicine, costutility studies are rare within plastic surgery, despite their capability of objectively comparing treatment options and assessing the societal costs of increasing a patient’s quality of life.1 Such studies can help physicians and society better understand the benefi ts that plastic surgery delivers for patients. Through the creation of a scoring tool, this study analyzes the design quality of the plastic surgery cost-utility literature.

An Analysis of the Plastic Surgery Cost-Utility Literature Using a Novel Scoring Tool

Background: Nerve decompression surgery has been successful in treating headaches refractory to traditional medical therapies. Nevertheless, a subset of patients remains unresponsive to surgical treatment. Methods: The authors conducted a retrospective chart review of the two senior authors’ (J.E.J. and W.G.A.) patient data from 2007 to 2020 to investigate differences in surgical outcomes in women reporting estrogen-associated headaches (headaches associated with menstrual period, oral contraceptives, pregnancy, or other hormonal drugs) compared with those who did not. For these two groups, the authors used the migraine headache index as the metric for headache severity and compared the mean percent change in migraine headache index score at 3 months and 1 year. Results: Of the 99 female patients who underwent nerve decompression surgery and met inclusion criteria, 50 reported estrogen-associated headaches and were found to have significantly earlier age of onset (p = 0.017) and initial presentation to clinic (p = 0.046). At 1 year postoperatively, migraine headache index score had improved more than 80 percent in the majority of patients (67 percent), but there was a subset of patients whose score improved less than 5 percent (12.5 percent). The authors did not find a significant difference in percent change in postoperative migraine headache index score between women with estrogen-associated headaches and those without such headaches. Conclusions: Women with estrogen-associated headaches have surgical outcomes comparable to those of women without this association. Nerve decompression surgery should be offered to women experiencing estrogen-associated headaches as an option for treatment. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

Estrogen-Associated Headaches Can Be Treated by Surgery: A Multicenter Retrospective Cohort Study

Purpose: Our lab has developed a novel cell therapy composed of genetically-modified autologous adipocytes. This process has been developed to enable intra-operative gene delivery via electroporation to obviate incubation times required for chemical or viral transfection. However, post-electroporation adipocyte apoptosis presents a challenge to efficient gene delivery. We hypothesize that delivery of poloxamer-188 (P188), a hydrophobic compound which stabilizes the cell membrane in the setting of electrical injury, can reduce post-electroporation apoptosis and improve overall gene delivery. Methods: Adipocytes were isolated from human abdominal subcutaneous fat (n=3) by a mechanical, collagenase-free method. Plasmids encoding peptide inhibitor of bone morphogenetic protein (BMP): CMV-Bmpr1afc was introduced into adipocytes by electroporation (20 ug plasmid DNA, 500 V/5 msec/4 pulses). Adipocytes were incubated with P188 (0.1% vol/vol) either 1) immediately prior to electroporation, 2) immediately after electroporation in culture media (Post-P188), or both before and after (Pre/Post-P188) (n=3). Control adipocytes were not treated with P188 at any time (n=3). mRNA was isolated from adipocytes and qPCR performed 7 days after electroporation to quantify pro-apoptotic (Bid and Casp3) gene expression with normalization (Actb). Culture media was collected weekly from day 7 through 28 after the electroporation, and ELISA were performed to quantify secreted BMPR1A-Fc. Results: Normalized Bid and Casp3 expression were significantly reduced with Post-P188 when compared with no P188 (Bid: 0.31 v. 1.00, p<0.01; Casp3: 0.44 v. 1.00, p<0.05). Similar results were obtained with Pre/Post-P188 treatment (Bid: 0.31 v. 1.00, p<0.01; Casp3: 0.34 v. 1.00, p<0.05). ELISA detected a significantly higher concentration of secreted BMPR1A-Fc with Post-P188 on day 7 (64.27 ng/ml v. 55.75 ng/ml, p<0.05) and day 14 (58.83 ng/ml v. 39.66 ng/ml, p<0.05). Interestingly, Pre-P188 resulted in reduced peptide secretion at day 7 (44.4 ng/ml v. 55.75 ng/ml, p<0.01) and day 14 (22.09 ng/ml v. 39.66 ng/ml, p<0.05). Conclusion: Our findings provide strong evidence that treatment with P188 can improve adipocyte survival after electroporation-mediated gene delivery. Specifically post-electroporation treatment with P188 results in elevated secretion levels which are sustained through 2 weeks in culture. Reduced peptide secretion observed with pre-electroporation P188 may be due to poor gene delivery into the cell caused by the improved cell membrane stabilization. The inclusion of post-electroporation P188 is likely to improve the efficacy of our desired cell therapy, and may have broader impact in laboratory approaches to cell transfection. 

William G. Austen

Papers

[Preservation of normal metabolism in isolated canine thyroid by pulsatile perfusion: preliminary study].

Abdominal Contouring Procedures Are Associated with a Physiologic Hypercoagulable State

An Analysis of the Plastic Surgery Cost-Utility Literature Using a Novel Scoring Tool

Estrogen-Associated Headaches Can Be Treated by Surgery: A Multicenter Retrospective Cohort Study

QS72. Post-electroporation Membrane Stabilization Improves Adipocyte Survival and Peptide Secretion After Gene Delivery