Hideaki Manabe

A further meta-analysis of population-based screening for abdominal aortic aneurysm

PURPOSE It remains unclear whether population-based screening for abdominal aortic aneurysm (AAA) in men reduces all-cause long-term mortality. We performed an updated meta-analysis of randomized controlled trials of AAA screening for prevention of long-term mortality in men. METHODS To identify all randomized controlled trials of population-based AAA screening with long-term (≥ 10 year) follow-up in men, MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials were searched through June 2009. Data regarding AAA-related and all-cause mortality (including Cox regression hazard ratios [HRs] and 95% confidence intervals [CIs]) were abstracted from each individual study. For each study, data regarding mortality in both the screening and control groups were used to generate odds ratios (ORs) and 95% CIs. Study-specific estimates were combined using inverse variance-weighted averages of logarithmic ORs or HRs (or risk ratios where no HR was reported) in both fixed- and random-effects models. RESULTS Our search identified four randomized controlled trials of population-based AAA screening with long-term follow-up in men aged ≥ 65 years. Pooled analysis demonstrated a statistically significant reduction in AAA-related mortality (random-effects OR, 0.55; 95% CI, 0.36 to 0.86; P = .008; P for heterogeneity = .01; absolute risk reduction [ARR], 4 per 1000; number needed to screen [NNS], 238; random-effects HR, 0.55; 95% CI, 0.35 to 0.86; P = .009; P for heterogeneity = .009) and revealed a statistically nonsignificant reduction (but a strong trend toward a significant reduction) in all-cause mortality (fixed-effects OR, 0.98; 95% CI, 0.95 to 1.00 [1.001]; P = .06; P for heterogeneity = .93; ARR, 5 per 1000; NNS, 217; fixed-effects HR, 0.98; 95% CI, 0.96 to 1.00 [1.0001]; P ≥ .05 [P = .052]; P for heterogeneity = .74) with AAA screening relative to control. CONCLUSION The results of our analysis suggest that population-based screening for AAA reduces AAA-related long-term mortality by 4 per 1000 over control in men aged ≥ 65 years. Whereas, screening for AAA shows a strong trend toward a significant reduction in all-cause long-term mortality by 5 per 1000, which does not narrowly reach statistical significance.

Review and Meta-Analysis of Randomized Controlled Clinical Trials of Remote Ischemic Preconditioning in Cardiovascular Surgery

To determine whether remote ischemic preconditioning (RIPC) is beneficial for patients who undergo cardiovascular surgery (CVS), a systematic review and meta-analysis of randomized controlled clinical trials of RIPC for the prevention of myocardial injury in CVS was performed. All prospective randomized controlled clinical trials of RIPC versus control that enrolled patients who underwent CVS were identified using a 2-level search strategy. First, a public-domain database (Medline) was searched using a Web-based search engine (PubMed). Second, relevant studies were identified through a manual search of secondary sources, including references of initially identified reports and a search of reviews and commentaries. The search identified 4 prospective randomized controlled clinical trials of RIPC versus control that enrolled patients who underwent CVS. In total, this meta-analysis included data on 184 patients who underwent CVS randomized to RIPC or control. Pooled analysis of the 4 trials demonstrated a statistically significant reduction in biomarkers of myocardial injury with RIPC relative to control (standardized mean difference -0.81, 95% confidence interval -1.29 to -0.33, p = 0.0010). In conclusion, the present study, the first systematic review and meta-analysis of randomized controlled clinical trials, demonstrated a statistically significant benefit of RIPC over control for reduction in biomarkers of myocardial injury in CVS patients.

Circulating matrix metalloproteinase-9 concentrations and abdominal aortic aneurysm presence: a meta-analysis.

To summarize the present evidence for an association between matrix metalloproteinase-9 (MMP-9) and abdominal aortic aneurysm (AAA) presence, we performed a meta-analysis of case-control studies that compared circulating MMP-9 concentrations between patients with AAA and subjects without AAA. MEDLINE database was searched to identify all case-control studies. For each study, data regarding serum or plasma MMP-9 concentrations in both the AAA and control groups were used to generate standardized mean differences (SMDs) and 95% confidence intervals (CIs). Study-specific estimates were combined using inverse variance-weighted average of logarithmic SMDs in both fixed- and random-effects models. Our search identified eight eligible studies including 580 patients with AAA and 258 subjects without AAA. Pooled analysis demonstrated significantly higher circulating MMP-9 concentrations in the AAA group than those in the control group in random-effect models (SMD, 0.70; 95% CI, 0.23-1.17; P=0.004). There was significant study heterogeneity of results (P<0.00001) but no evidence of significant publication bias (P=0.1376). We found that, based on a systematic review and meta-analysis, circulating MMP-9 concentrations are higher in patients with AAA than those in subjects without AAA. Higher circulating MMP-9 concentrations are associated with AAA presence.

A contemporary meta-analysis of Dacron versus polytetrafluoroethylene grafts for femoropopliteal bypass grafting

BACKGROUND The present study provides a contemporary and comprehensive summation of midterm patency rates of polyester (Dacron) or polytetrafluoroethylene (PTFE) grafts in femoropopliteal bypass grafting based on a meta-analysis consisting only of randomized controlled trials. METHODS MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched to identify all randomized controlled trials of Dacron vs PTFE grafts in femoropopliteal bypass grafting. Seven trials were found. Survival data were combined to yield the pooled cumulative primary patency. We estimated the log hazard ratio (HR) for each 1-month interval and then combined the HRs in a stratified way across intervals to obtain an overall log HR for each trial. Study-specific estimates were combined using inverse variance-weighted averages of logarithmic HRs in fixed-effects and random-effects models. RESULTS The pooled cumulative primary patency of Dacron and PTFE grafts was, respectively, 60.2% (95% confidence interval [CI], 56.4%-64.0%) and 53.8% (95% CI, 46.8%-60.9%) at 3 years, and 49.2% (95% CI, 45.6%-52.7%) and 38.4% (95% CI, 32.2%-44.6%) at 5 years. Pooled analysis of the seven trials demonstrated no difference in HR for graft occlusion with Dacron relative to PTFE grafts (random-effects HR, 0.87; 95% CI, 0.67-1.12; P = .27 for effect; P = .03 for heterogeneity). CONCLUSION Either Dacron or PTFE grafts can be used in femoropopliteal bypass grafting with no significant differences in midterm graft patency at 5 years (49.2% vs 38.4%) when the autologous saphenous vein is unavailable.

Aprotinin increases mortality as compared with tranexamic acid in cardiac surgery: a meta-analysis of randomized head-to-head trials

To determine whether aprotinin increases mortality as compared with tranexamic acid in cardiac surgery, we performed a meta-analysis of randomized head-to-head trials. All prospective randomized head-to-head trials of aprotinin vs. tranexamic acid enrolling patients undergoing cardiac surgery were identified using a web-based search engine (PubMed). For each study, data regarding mortality in both the aprotinin and tranexamic acid groups were used to generate risk ratios (RRs) and 95% confidence intervals (CIs). Study-specific estimates were combined using inverse variance-weighted averages of logarithmic RRs in random-effects models. Our search identified nine trials (eight trials included in the previous meta-analysis and the blood conservation using antifibrinolytics in a randomized trial [BART] study). Seven trials were composed of low-risk patients (n=1291) and two trials consisted of low-risk patients (n=1628). Pooled analysis of the nine trials demonstrated a statistically significant 45% increase in mortality with aprotinin relative to tranexamic acid therapy (RR, 1.45; 95% CI, 1.00 [1.0002]-2.11; P=0.05 [0.0499]). The present meta-analysis of updated all randomized head-to-head trials, the best evidence, demonstrated a statistically significant increase in mortality with aprotinin relative to tranexamic acid therapy in cardiac surgery.

Circulating lipoprotein(a) concentrations and abdominal aortic aneurysm presence.

To summarize the present evidence for an association between circulating lipoprotein(a) [Lp(a)] and abdominal aortic aneurysm (AAA) presence. MEDLINE database was searched to identify all case-control studies that compared circulating Lp(a) concentrations between patients with AAA and subjects without AAA. For each study, data regarding Lp(a) concentrations in both the AAA and control groups were used to generate standardized mean differences (SMDs) and 95% confidence intervals (CIs). Study-specific estimates were combined using inverse variance-weighted average of logarithmic SMDs in both fixed- and random-effects models. Our search identified five case-control studies. In total, our meta-analysis included data on 982 cases with AAA and 1296 controls without AAA. Pooled analysis of the five studies demonstrated significantly higher Lp(a) concentrations in the AAA group than those in the control group in random-effect models (SMD, 0.26; 95% CI, 0.08-0.44; P=0.005). There was significant study heterogeneity of results (P=0.03) but no evidence of significant publication bias (P=0.3272). We found that circulating Lp(a) concentrations are likely higher in cases with AAA than in controls without AAA. Higher circulating Lp(a) concentrations may be associated with AAA presence.

Two-stage portal vein ligation facilitates liver regeneration in rats.

Background/Aims: Recent reports have demonstrated that some patients are unable to undergo scheduled liver resection after preoperative portal vein embolization due to insufficient hypertrophy of the future remnant liver. The present study examined whether two-stage portal vein ligation (PVL) increases hypertrophy of the future remnant liver compared to conventional PVL in rats. Methods: Rats were divided into 3 groups: group A, ligation of left primary branch; group B, ligation of right and left primary branches; group C, ligation of the left primary branch, followed by 2-stage PVL 7 days postoperatively. To evaluate liver regeneration, the proliferating cell nuclear antigen labeling index (LI), mitotic index (MI) in the caudate lobe and weight ratio of caudate lobe to body weight were measured. Results: The weight ratio of caudate lobe to body weight was significantly higher in group C than in groups A or B 14 days postoperatively. In groups A and B, LI and MI in the caudate lobe peaked 2 days postoperatively, then decreased to preoperative levels by 7–8 days postoperatively, but remained significantly elevated until 10–14 days postoperatively in group C. Conclusion: Two-stage PVL increases hypertrophy of the future remnant liver compared to conventional PVL in rats.

Plasma Tissue Plasminogen Activator and Abdominal Aortic Aneurysm Presence: A Systematic Review and Meta-analysis

BACKGROUND To summarize the present evidence for an association between circulating tissue plasminogen activator (tPA) levels and abdominal aortic aneurysm (AAA) presence, we performed a systematic review and meta-analysis of case-control studies that compared plasma tPA levels between patients with AAA and subjects without AAA. METHODS MEDLINE was searched to identify all case-control studies that compared plasma tPA levels between patients with AAA and subjects without AAA. For each study, data regarding plasma tPA levels in both the AAA and control groups were used to generate standardized mean differences and 95% confidence intervals. Study-specific estimates were combined using inverse variance-weighted average of logarithmic standardized mean differences in both fixed- and random-effects models. RESULTS Our search identified five eligible case-control studies, including data on 234 patients with AAA and 459 subjects without AAA. Pooled analysis of the five studies demonstrated nonsignificantly higher plasma tPA levels in the AAA group than those in the control group in fixed-effect models (standardized mean differences = 0.07; 95% confidence interval = -0.09-0.24; p = 0.40). There was minimal study heterogeneity of results (p = 0.05) and no evidence of significant publication bias (p = 0.3272). CONCLUSION The results of our analysis suggest that plasma tPA levels may not be higher in patients with AAA than those in subjects without AAA. Higher plasma tPA levels may not be associated with AAA presence.

Regarding "C-reactive protein (CRP) elevation in patients with abdominal aortic aneurysm".

Badger et al demonstrated in their case-control study that C-reactive protein (CRP) concentration was higher in patients with abdominal aortic aneurysm (AAA) than that in subjects without AAA (385.0 L/dL [95% confidence interval, 310.4442.8] vs 18.03 L/dL [168.1-196.9]). It has been, however, controvertible whether higher CRP concentration is associated with AAA presence. To summarize the present evidence for an association between CRP and AAA presence, we performed a meta-analysis of case-control studies that compared CRP concentration between patients with AAA and subjects without AAA. Our comprehensive search identified six case-control studies that compared CRP concentration between patients with AAA and patients without AAA. In total, our meta-analysis included data on 744 cases with AAA and 1,288 controls without AAA. Pooled analysis of the six studies demonstrated significantly higher CRP concentration in the AAA group than that in the control group in random-effect models (pooled standardized mean difference [SMD], 0.50; 95% confidence interval [CI], 0.09 to 0.91; P .02) (Fig). There was significant study heterogeneity of results analyzed by means of standard 2 tests (P .00001) and accordingly a little difference in the pooled result from fixed-effects modeling (pooled SMD, 0.36; 95% CI, 0.27 to 0.46; P .00001). Sensitivity analyses were performed to assess the contribution of each study to the pooled estimate by excluding individual studies one at a time and recalculating the pooled SMD estimates for the remaining studies. Exclusion of the study by Dawson et al (pooled SMD, 0.54; 95% CI, 0.08 to 0.99; P .02), Golledge et al (pooled SMD, 0.60; 95% CI, 0.13 to 1.07; P .01), Wanhainen et al (pooled SMD, 0.60; 95% CI, 0.13 to 1.07; P .01), or Powell et al (pooled SMD, 0.47; 95% CI, 0.02 to 0.93; P .04) from the analysis did not substantively alter the overall result of our analysis. Meanwhile, eliminating the study by Badger et al (pooled SMD, 0.48; 95% CI, –0.11 to 1.07; P .11) or Alberto et al (pooled SMD, 0.30; 95% CI, –0.02 to 0.62; P .07) substantially changed the pooled point estimate (no significant difference between CRP concentration in the AAA and control group). There was no evidence of significant publication bias using an adjusted rank-correlation test (P .0909). The results of our analysis suggest that CRP concentration in patients with AAA may be higher than that in patients without AAA, though several sensitivity analyses substantially changed the pooled point estimate. Despite the results of the present metaanalysis and the study by Badger et al, however, further studies may be needed to confirm whether higher CRP concentration is associated with AAA presence.

Effects of omentopexy combined with granulocyte colony-stimulating factor in a rabbit heart model

OBJECTIVE We investigated whether omentopexy combined with subcutaneously administered granulocyte colony-stimulating factor (G-CSF) reduces infarction areas and improves left ventricular dysfunction in a rabbit model of coronary occlusion and reperfusion. METHODS A coronary artery of a male Japanese white rabbit was ligated for 30 min and then reperfused. An omental pedicle graft was fixed onto the myocardial ischemic area after abrading the epicardium. G-CSF (10 μg kg(-1)day(-1)) was subcutaneously administered for 5 days postoperatively. Animals were assigned to groups (n = 7 per group) as follows: group N, saline; group O, omentopexy and saline; group G, G-CSF; and group OG, omentopexy and G-CSF. At 4 weeks postoperatively, left ventricular ejection fraction and left ventricular end-diastolic diameter were evaluated by echocardiography. Harvested left ventricles were stained with Evans blue and triphenyltetrazolium chloride to measure necrotic and fibrotic areas. The arteriolar density in ischemic and nonischemic areas was evaluated. At 7 days postoperatively, the intrathoracic omentum was evaluated (n = 6 per group). RESULTS Echocardiography at 4 weeks postoperatively revealed significant improvement in the left ventricular dysfunction of group OG. Necrosis and fibrosis in ischemic areas were significantly reduced in groups G and OG. Arteriolar density in the ischemic area and intrathoracic omentum weight were increased largely in group OG than in the other groups. CONCLUSIONS Omentopexy with G-CSF offers more potential benefits for the ischemic heart than G-CSF alone.