In a placebo-controlled trial, 497 patients undergoing vascular surgery were randomly assigned to receive either fluvastatin or placebo, both before surgery and for 30 days after surgery. ...Postoperative myocardial ischemia occurred significantly less frequently in the fluvastatin group. Fluvastatin was also associated with a reduction in the rate of death from cardiovascular causes or myocardial infarction.
In patients undergoing vascular surgery, postoperative myocardial ischemia occurred significantly less frequently in the fluvastatin group than in the placebo group. Fluvastatin was also associated with a reduction in the rate of death from cardiovascular causes or myocardial infarction.
Patients with atherosclerotic vascular disease who undergo noncardiac vascular surgery are at high risk for postoperative cardiac events, such as myocardial infarction and death from cardiovascular causes. Cardiac events occur in up to 24% of patients in high-risk cohorts
1
and are related to the high incidence of underlying coronary artery disease. Hertzer et al., performing routine coronary angiography in 1000 patients scheduled for vascular surgery, found that only 8% had a normal coronary-artery tree.
2
Although the pathophysiology of perioperative myocardial infarction is not entirely understood, it is well accepted that rupture of coronary plaque, leading to thrombus formation and subsequent . . .
Defective homologous recombination (HR) DNA repair imposed by BRCA1 or BRCA2 deficiency sensitizes cells to poly (ADP-ribose) polymerase (PARP)-1 inhibition and is currently exploited in clinical ...treatment of HR-deficient tumors. Here we show that mild hyperthermia (41–42.5 °C) induces degradation of BRCA2 and inhibits HR. We demonstrate that hyperthermia can be used to sensitize innately HR-proficient tumor cells to PARP-1 inhibitors and that this effect can be enhanced by heat shock protein inhibition. Our results, obtained from cell lines and in vivo tumor models, enable the design of unique therapeutic strategies involving localized on-demand induction of HR deficiency, an approach that we term induced synthetic lethality.
Endovascular repair of abdominal aortic aneurysms avoids much of the risk associated with conventional surgical repair. In two randomized trials, this technique has been shown to be associated with ...lower rates of perioperative morbidity and mortality. Longer-term follow-up data from one of these trials (the Dutch Randomized Endovascular Aneurysm Management DREAM trial) show that the survival advantage of endovascular repair is not sustained after the first postoperative year.
Endovascular repair of abdominal aortic aneurysms has been shown to be associated with lower rates of perioperative morbidity and mortality. Longer-term follow-up data show that the survival advantage of endovascular repair is not sustained after the first postoperative year.
Two randomized trials have demonstrated better outcomes with elective endovascular repair of abdominal aortic aneurysms than with conventional open repair in the first month after the procedure.
1
,
2
The reported in-hospital mortality rates in these two trials were 4.6 percent and 6.0 percent for open repair and 1.6 percent and 1.2 percent for endovascular repair, respectively. Although the relevance of a reduction in perioperative risk should not be underestimated from the patient's perspective, the improvement in early survival with the use of a less invasive technique is not surprising.
3
Consequently, both reports stressed the need for longer-term data before a . . .
The efficacy and need for secondary interventions for type II endoleaks following endovascular abdominal aortic aneurysm repair (EVAR) remain controversial. This systematic review aimed at ...investigating the clinical outcomes of different type II endoleak treatments in patients with a persistent type II endoleak after EVAR.
Embase, Medline via Ovid, Web of Science Core Collection, the Cochrane CENTRAL, and Google Scholar.
This systematic review was performed in accordance with the PRISMA Statement. Outcomes of interest were technical and clinical success, change in sac diameter, complications, need for additional interventions, abdominal aortic aneurysm (AAA) rupture, and (AAA related) mortality. Meta-analyses were performed with random effects models.
A total of 59 studies were included, with a cumulative cohort of 1073 patients with persistent type II endoleak. Peri-operative complications following treatment of type II endoleaks occurred in 3.8% of patients (95% CI 2.7–5.2%), and AAA related mortality was 1.8% (95% CI 1.1–2.7%). Overall technical success was 87.9% (95% CI 83.1–92.1%), while clinical success was 68.4% (95% CI 61.2–75.1%). Among studies detailing sac dynamics, decrease or stable sac, with or without resolution, was achieved in 78.4% (95% CI 70.2–85.6%). Changes in sac diameter following type II endoleak treatment were documented in 157 patients to at least 24 months. Within this group an actual decrease in sac diameter was reported in only 27 of 40 patients.
There is little evidence supporting the efficacy of secondary intervention for type II endoleaks after EVAR. Although generally safe, the lack of evidence supporting the efficacy of type II endoleak treatment leads to difficulty in assessing its merits.
Abdominal aortic calcification (AAC) is a common finding in patients with atherosclerosis.
The aim of this study was to demonstrate the incremental value of AAC in predicting long term cardiovascular ...(CV) outcome by conducting a meta-analysis of observational studies.
MEDLINE and Cochrane databases.
Longitudinal studies with at least 2 years of follow-up, reporting the influence of AAC on CV outcome of general population patients.
Four separate end points-coronary events, cerebrovascular events, all CV events and CV related death-were tested for their relationship with AAC at baseline, using weighted random effects meta-analysis. Heterogeneity was calculated using Q and I(2) statistic tests. Publication bias was assessed by funnel plot symmetry and trim and fill methods. The importance of calcium quantification was also explored (sensitivity analysis).
10 studies were included. An increased relative risk (RR) was found for all end points: for coronary events (five studies, n=11250) 1.81 (95% CI 1.54 to 2.14); for cerebrovascular events (four studies, n=9736) 1.37 (1.22 to 3.54); for all CV events (four studies, n=4960) 1.64 (1.24 to 2.17); and for CV death (three studies, n=4986) 1.72 (1.03 to 2.86). Analysis of studies presenting results in categories (no/minimal, moderate and severe calcification) revealed a stepwise increase in the RR for all end points. Significant heterogeneity was found in the included studies. Sources of heterogeneity were identified in the publication date, duration of follow-up, and mean age and gender differences in the included patient cohorts.
Existing data suggest that AAC is a strong predictor of CV related events or death in the general population. The predictive impact is greater in more calcified aortas. The generalisability of the meta-analysis is limited by heterogeneity in the coronary events, all CV events and CV death end points.
Background Bowel ischemia is a rare but devastating complication after abdominal aortic aneurysm (AAA) repair. Its rarity has prohibited extensive risk-factor analysis, particularly since the ...widespread adoption of endovascular AAA repair (EVAR); therefore, this study assessed the incidence of postoperative bowel ischemia after AAA repair in the endovascular era and identified risk factors for its occurrence. Methods All patients undergoing intact or ruptured AAA repair in the Vascular Study Group of New England (VSGNE) between January 2003 and November 2014 were included. Patients with and without postoperative bowel ischemia were compared and stratified by indication (intact and ruptured) and treatment approach (open repair and EVAR). Criteria for diagnosis were endoscopic or clinical evidence of ischemia, including bloody stools, in patients who died before diagnostic procedures were performed. Independent predictors of postoperative bowel ischemia were established using multivariable logistic regression analysis. Results Included were 7312 patients, with 6668 intact (67.0% EVAR) and 644 ruptured AAA repairs (31.5% EVAR). The incidence of bowel ischemia after intact repair was 1.6% (open repair, 3.6%; EVAR, 0.6%) and 15.2% after ruptured repair (open repair, 19.3%; EVAR, 6.4%). Ruptured AAA was the most important determinant of postoperative bowel ischemia (odds ratio OR, 6.4, 95% confidence interval CI, 4.5-9.0), followed by open repair (OR, 2.9; 95% CI, 1.8-4.7). Additional predictive patient factors were advanced age (OR, 1.4 per 10 years; 95% CI, 1.1-1.7), female gender (OR, 1.6; 95% CI, 1.1-2.2), hypertension (OR, 1.8; 95% CI, 1.1-3.0), heart failure (OR, 1.8; 95% CI, 1.2-2.8), and current smoking (OR, 1.5; 95% CI, 1.1-2.1). Other risk factors included unilateral interruption of the hypogastric artery (OR, 1.7; 95% CI, 1.0-2.8), prolonged operative time (OR, 1.2 per 60-minute increase; 95% CI, 1.1-1.3), blood loss >1 L (OR, 2.0; 95% CI, 1.3-3.0), and a distal anastomosis to the femoral artery (OR, 1.7; 95% CI, 1.1-2.7). Bowel ischemia patients had a significantly higher perioperative mortality after intact (open repair: 20.5% vs 1.9%; P < .001; EVAR: 34.6% vs 0.9%; P < .001) as well as after ruptured AAA repair (open repair: 48.2% vs 25.6%; P < .001; EVAR: 30.8% vs 21.1%; P < .001). Conclusions This study underlines that although bowel ischemia after AAA repair is rare, the associated outcomes are very poor. The cause of postoperative bowel ischemia is multifactorial and can be attributed to patient factors and operative characteristics. These data should be considered during preoperative risk assessment and for optimization of both the patient and the procedure in an effort to reduce the risk of postoperative bowel ischemia.
Genetic causes for abdominal aortic aneurysm (AAA) have not been identified and the role of genes associated with familial thoracic aneurysms in AAA has not been explored. We analyzed nine genes ...associated with familial thoracic aortic aneurysms, the vascular Ehlers–Danlos gene
COL3A1
and the
MTHFR
p.Ala222Val variant in 155 AAA patients. The thoracic aneurysm genes selected for this study were the transforming growth factor-beta pathway genes
EFEMP2, FBN1, SMAD3, TGBF2, TGFBR1, TGFBR2,
and the smooth muscle cells genes
ACTA2, MYH11
and
MYLK
. Sanger sequencing of all coding exons and exon–intron boundaries of these genes was performed. Patients with at least one first-degree relative with an aortic aneurysm were classified as familial AAA (
n
= 99), the others as sporadic AAA. We found 47 different rare heterozygous variants in eight genes: two pathogenic, one likely pathogenic, twenty-one variants of unknown significance (VUS) and twenty-three unlikely pathogenic variants. In familial AAA we found one pathogenic and segregating variant (
COL3A1
p.Arg491X), one likely pathogenic and segregating (
MYH11
p.Arg254Cys), and fifteen VUS. In sporadic patients we found one pathogenic (
TGFBR2
p.Ile525Phefs*18) and seven VUS. Thirteen patients had two or more variants. These results show a previously unknown association and overlapping genetic defects between AAA and familial thoracic aneurysms, indicating that genetic testing may help to identify the cause of familial and sporadic AAA. In this view, genetic testing of these genes specifically or in a genome-wide approach may help to identify the cause of familial and sporadic AAA.
Objective In patients undergoing endovascular aneurysm repair (EVAR), the postimplantation syndrome (PIS), comprising fever and inflammation, occurs frequently. The cause of PIS is unclear, but graft ...composition and acute thrombus formation may play a role. The objective of this study was to evaluate these possible causes of the inflammatory response after EVAR. Methods One hundred forty-nine patients undergoing elective EVAR were included. Implanted stent grafts differed mainly in the type of fabric used: either woven polyester (n = 82) or expanded polytetrafluorethylene (ePTFE; n = 67). Tympanic temperature and C-reactive protein (CRP) were assessed daily during hospitalization. PIS was defined as the composite of a body temperature of ≥38°C coinciding with CRP >10 mg/L. Besides graft composition, the size of the grafts and the volume of new-onset thrombus were calculated using dedicated software, and results were correlated to PIS. Results Implantation of grafts made of polyester was associated with higher postoperative temperature ( P < .001), CRP levels ( P < .001), and incidence of PIS (56.1% vs 17.9%; P < .001) compared to ePFTE. After multivariate analysis, woven polyester stent grafts were independently associated with an increased risk of PIS (hazard ratio, 5.6; 95% confidence interval, 1.6-19.4; P = .007). Demographics, amount of graft material implanted, or new-onset thrombus had no association with PIS. Conclusions The composition of stent grafts may play a material role in the incidence of postimplantation syndrome in patients undergoing EVAR. Implantation of stent grafts based on woven polyester was independently associated with a stronger inflammatory response.
The purpose of this study was to report the incidence, natural history, and outcome of type II endoleaks in the largest prospective real-world cohort to date.
Patients were extracted from the ...prospective Endurant Stent Graft Natural Selection Global Postmarket Registry (ENGAGE). Two groups were analyzed: first, patients with an isolated type II endoleak; and second, patients with a type II endoleak who later presented with a type I endoleak. A health status analysis between patients with an early type II endoleak and patients with no endoleak was performed. Second, an attempt was made to identify risk factors in patients with a type II endoleak who later presented with a type I endoleak.
Through 5 years of follow-up, a total of 197 (15.6%) patients with isolated type II endoleaks were identified. Most were detected within the first 30 days (n = 73 37.1%) and through the first year (n = 73 37.1%), with the remainder being detected after 1 year of follow-up (n = 51 25.8%). Patients with a type II endoleak had a higher incidence of aneurysm growth and more secondary endovascular procedures (15.4% vs 7.5% at 5 years; P < .001). Overall survival was higher in the isolated type II endoleak group compared with patients with no endoleak (77.2% vs 67.0% at 5 years; P = .010). Twenty-two patients (10%) with a type II endoleak were diagnosed with a late type I endoleak (type IA, n = 10; type IB, n = 12), with a secondary intervention rate of 67.5% through 5 years. There was no difference in health status scores between patients with an early type II endoleak and patients without any type of endoleak at 1-year follow-up.
In the ENGAGE registry, isolated type II endoleaks are present in 15.6% of patients during follow-up. The majority do not require secondary intervention, and an early isolated type II endoleak does not have an impact on health status through 1 year. However, a small group of patients with a type II endoleak will present with a type I endoleak, resulting in a high secondary intervention rate and significant risk of aneurysm-related complications.
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Introduction
Aging of the worldwide population has been observed, and postoperative outcomes could be worse in elderly patients. This nationwide study assessed trends in number of surgical resections ...in octogenarians regarding various major surgical procedures and associated postoperative outcomes.
Methods
All patients who underwent surgery between 2014 and 2018 were included from Dutch nationwide quality registries regarding esophageal, stomach, pancreas, colorectal liver metastases, colorectal cancer, lung cancer and abdominal aortic aneurysms (AAA). For each quality registry, the number of patients who were 80 years or older (octogenarians) was calculated per year. Postoperative outcomes were length of stay (LOS), 30 day major morbidity and 30 day mortality between octogenarians and younger patients.
Results
No increase in absolute number and proportion of octogenarians that underwent surgery was observed. Median LOS was higher in octogenarians who underwent surgery for colorectal cancer, colorectal liver metastases, lung cancer, pancreatic disease and esophageal cancer. 30 day major morbidity was higher in octogenarians who underwent surgery for colon cancer, esophageal cancer and elective AAA-repair. 30 day mortality was higher in octogenarians who underwent surgery for colorectal cancer, lung cancer, stomach cancer, pancreatic disease, esophageal cancer and elective AAA-repair. Median LOS decreased between 2014 and 2018 in octogenarians who underwent surgery for stomach cancer and colorectal cancer. 30 day major morbidity decreased between 2014 and 2018 in octogenarians who underwent surgery for colon cancer. No trends were observed in octogenarians regarding 30 day mortality between 2014 and 2018.
Conclusion
No increase over time in absolute number and proportion of octogenarians that underwent major surgery was observed in the Netherlands. Postoperative outcomes were worse in octogenarians.
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