Abstract Background High-field intraoperative magnetic resonance imaging (iMRI) has been studied in two single-centre randomised trials with patients who have glioblastoma and is hypothesised to ...enable a greater extent of tumour resection and prolong survival in patients with gliomas. iMRI for glioblastomas has also been shown to be significantly superior to 5-ALA and white-light surgery. However, the real value of iMRI is still a controversial issue. Given that use of this technology is relatively expensive, a high-quality prospective randomised trial is necessary before the approach can be made widely available. We have undertaken a single-centre prospective, randomised controlled trial to assess the clinical efficacy of 3.0T iMRI-guided resection of malignant gliomas compared with conventional neuronavigation only. Here we present the interim analysis of a long-term follow-up of patients with high-grade gliomas. Methods Eligible patients were aged 18–70 years with suspected (as assessed by consaltant surgeon), newly diagnosed malignant supratentorial glioma, met the Karnofsky performance scale 70 or above, and for whom gross total resection was intended. Patients were excluded if they had: tumour of the midline, basal ganglia, cerebellum, or brain stem; MRI contraindications; inability to give informed consent; renal or hepatic insufficiency; history of malignant tumours of other systems; or pathology other than astrocytoma, oligodendroglioma, or oligoastoryctoma (WHO grade II to IV). All participants were randomly assigned to either the trial group (iMRI group) or control group (conventional neuronavigation group) after giving written consent. All surgical protocols including conventional neuro-navigation are identical between the two groups; iMRI is specifically used in the trial group. The estimated sample size was 303 patients in the intent-to-treat analysis to give 80% complete power with a type I error of 0·05. Computational randomisation was done when maximal safe resection was achieved by the masked surgeons. The primary endpoint was extent of tumour resection. The secondary endpoints were progression-free survival and overall survival. This trial is registered with ClinicalTrial.gov , number NCT01479686 . This study was approved by the Huashan Institutional Review Board. Written informed consents were given by patients or their attorneys before surgery. Findings Between March, 2012, and August, 2015, we enrolled 202 patients, 11 of whom were subsequently excluded because of unbefitting pathology. 177 patients were followed-up more than 6 months and subsequently analysed. 190 patients had low-grade gliomas (51 males vs 39 females, mean age 38·55 years SD 9·56), and 87 patients had high-grade gliomas (56 males vs 31 females, mean age 50·42 years 12·18). 43 of the patients with high-grade gliomas were enrolled in the iMRI group, and 44 patients with high-grade gliomas were enrolled in the control group. The extent of tumour resection (iMRI median 100% IQR 70·87–100 vs control median 98·76% 51·81–100) and the rate of gross total resection (86% vs 45%) were higher in the iMRI group than that in the control group (p<0·0001). Patients in the iMRI group who had eloquent high-grade gliomas had significantly longer progression-free survival (median not reached vs 13·2 months, p=0·012) and overall survival (median not reached vs 21·5 months, p=0·003) than patients in the control group. No events were identified as side-effects of iMRI. Interpretation The results address hypotheses about the clinical benefits of 3.0T iMRI-guided maximal safe resection of glioma. It is practical to increase the extent of tumour resection for high-grade gliomas to prolong progression-free survival and overall survival, especially for eloquent high-grade gliomas. Funding National Key Technology R&D Program of China (No. 2014BAI04B05) and the Shanghai Municipal Health Bureau (XBR2011022).
Objectives The present study aimed to establish a risk score using a simple calculation with an enhanced predictive value for major adverse cardiac events (MACE) in patients with unprotected ...left main coronary artery (UPLMCA) disease after the implantation of a drug-eluting stent (DES). Background The anatomic-, clinical-, and procedure-based NERS (New Risk Stratification) score was superior to the SYNTAX (Synergy Between Percutaneous Coronary Intervention With TAXUS and Cardiac Surgery) score in predicting MACE after stenting UPLMCA. The complexity of the calculation was its major limitation. Methods The NERS score II was derived from our previous 2 studies and externally compared with the NERS and SYNTAX scores in 1,463 patients with UPLMCA disease who underwent implantation of a DES in a prospective, multicenter registry trial. The primary endpoint was MACE at 1 year after the index procedure, including myocardial infarction, cardiac death, and target vessel revascularization. Results The NERS score II system consisted of 16 (7 clinical and 9 angiographic) variables. A NERS score II ≥19 demonstrated enhanced MACE sensitivity and specificity of 84.0% and 76.0% (MACE as the state variable), respectively, which were similar to the NERS score but significantly higher compared with the SYNTAX score. A NERS score II ≥19 was the only independent predictor of cumulative MACE (hazard ratio: 3.27; 95% confidence interval CI: 1.86 to 5.23; p ≤ 0.001) and stent thrombosis (odds ratio: 22.15; 95% CI: 12.47 to 57.92; p ≤ 0.001) at follow-up. Conclusions The NERS score II, similar to the conventional NERS score, is more predictive of MACE than the SYNTAX score in UPLMCA patients after implantation of a DES.
Abstract Background Postoperative cognitive dysfunction, a common complication after surgery in elderly patients, is an increasing and largely underestimated problem without a defined etiology. ...Neuroinflammation plays an important role in the pathogenesis of postoperative cognitive dysfunction. The present study sought to investigate the role of neuroinflammation mediated by high-mobility group box 1 (HMGB1), S100B, and the receptor for advanced glycation end product (RAGE) in cognitive dysfunction after partial hepatectomy in aged mice. Materials and methods Old C57BL/6 mice were randomly divided into three groups: normal control ( n = 18), anesthetic ( n = 66), and surgery ( n = 66). The mice in the surgery or anesthetic group received isoflurane anesthesia for either partial hepatectomy or no surgery, respectively. Cognitive function was subsequently assessed using a Y -maze. HMGB1, S100B, RAGE, interleukin-1β, and nuclear factor-kappaB p65 levels were measured at 12 h and 1, 3, and 7 d after surgery. Immunofluorescence double labeling was performed to study the colocalization between RAGE and its ligands, HMGB1 and S100B. Results The mice’s learning and memory abilities were significantly impaired at 1 and 3 d and 2 and 4 d after surgery, respectively. The expression of HMGB1, S100B, RAGE, and nuclear factor-kappaB p65 had increased significantly at 12 h and 1 and 3 d after surgery. The interleukin-1β level was significantly increased at 1 and 3 d after surgery. The interaction of HMGB1 or S100B with RAGE was confirmed at 1 d after surgery. Conclusions These data suggest that HMGB1, S100B, and RAGE signaling modulate the hippocampal inflammatory response and might play key roles in surgery-induced cognitive decline.
Abstract Objectives The present study established criteria to differentiate simple from complex bifurcation lesions and compared 1-year outcomes stratified by lesion complexity after provisional ...stenting (PS) and 2-stent techniques using drug-eluting stents. Background Currently, no criterion can distinguish between simple and complex coronary bifurcation lesions. Comparisons of PS and 2-stent strategies stratified by lesion complexity have also not been reported previously. Methods Criteria of bifurcation complexity in 1,500 patients were externally tested in another 3,660 true bifurcation lesions after placement of drug-eluting stents. The primary endpoint was the occurrence of a major adverse cardiac event (MACE) at 12 months. The secondary endpoint was the rate of stent thrombosis (ST). Results Complex (n = 1,108) bifurcation lesions were associated with a higher 1-year rate of MACE (16.8%) compared with simple (n = 2,552) bifurcation lesions (8.9%) (p < 0.001). The in-hospital ST and 1-year target lesion revascularization rates after 2-stent techniques in the simple group (1.0% and 5.6%, respectively) were significantly different from those after PS (0.2% p = 0.007 and 3.2% p = 0.009, respectively); however, 1-year MACE rates were not significantly different between the 2 groups. For complex bifurcation lesions, 2-stent techniques had lower rates of 1-year cardiac death (2.8%) and in-hospital MACE (5.0%) compared with PS (5.3%, p = 0.047; 8.4%, p = 0.031). Conclusions Complex bifurcation lesions had higher rates of 1-year MACE and ST. The 2-stent and PS techniques were overall equivalent in 1-year MACE. However, 2-stent techniques for complex lesions elicited a lower rate of cardiac death and in-hospital MACE but higher rates of in-hospital ST and revascularization at 1 year for simple lesions.
Abstract Background The results of SYNTAX trial have been reported based on “corelab” calculated SS (cSS). It has been shown that reproducibility of SS is better among the core laboratory technicians ...than interventional cardiologists. Thus, the prognostic value and clinical implication of the “site” SYNTAX SS (sSS) remain unknown. Objectives The study sought to evaluate the prognostic value and clinical implication of the sSS after percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery in the randomized SYNTAX trial. Methods The sSS was calculated by the site investigators before randomization in the SYNTAX trial. New tertiles based on the sSS were defined with low (0 to 19), intermediate (20 to 27), and high (≥28) scores. The clinical endpoints were compared between PCI and CABG by Kaplan-Meier estimates, log-rank comparison, and Cox regression analyses using the new tertiles. The sSS-based SS II was calculated and its predictive performance was evaluated. Results The mean difference in cSS and sSS is 3.8 ± 11.2, with a mean absolute difference of 8.9 ± 7.8. In the overall cohort, using sSS there was a higher incidence of major adverse cardiac and cerebrovascular events (MACCE) at 5-year follow-up in the PCI group for low (31.9% vs. 24.5%; p = 0.054), intermediate (39.5% vs. 29.5%; p = 0.019), and high (43.0% vs. 31.4%; p = 0.003) tertiles, compared with the CABG group. Similarly, in the 3-vessel disease subgroup, 5-year MACCE rates were higher in PCI group in all tertiles. Conversely, in the left main subgroup, MACCE rates were similar for PCI and CABG groups in all tertiles. The sSS-based SS II (c-index: 0.736) had predictive performance similar to the cSS-based SS II (c-index: 0.744), with net reclassification index of –0.0062 (p = 0.79). Conclusions Appropriate training and unbiased assessment are needed when using SS in clinical decision making. sSS and tertiles based on sSS showed poor discrimination among low, intermediate, and high-risk groups. However, combining clinical factors with sSS retained the predictive performance of SS II. (SYNTAX Study: TAXUS Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries; NCT00114972 )
Abstract Background Cigarette smoking is a well-known risk factor for development of coronary artery disease (CAD). However, some studies have suggested a “smoker’s paradox,” meaning neutral or ...favorable outcomes in smokers who have developed CAD, especially myocardial infarction (MI). Objectives The study aimed to examine the association of smoking status with clinical outcomes in the randomized controlled SYNTAX (SYNergy Between PCI With TAXUS and Cardiac Surgery) trial at 5-year follow-up. Methods Detailed smoking history was collected at baseline, 6-month, 1-year, 3-year, and 5-year follow-up. The composite endpoints included death/MI/stroke (primary endpoint) plus major adverse cardiac and cerebrovascular events (MACCE) (combination of death/MI/stroke and target lesion revascularization) according to patient smoking status. The comparison of 5-year clinical outcomes between the groups according to smoking status was performed with Cox regression using smoking status at baseline or smoking as a time-dependent covariate. Results A sizeable proportion (n = 322, 17.9%) of patients had changing smoking status during 5-year follow-up. One in 5 patients with complex CAD was smoking at baseline. However, 60% stopped after revascularization while others continued to smoke. Smokers had worse clinical outcomes due to a higher incidence of recurrent MI in both revascularization arms. Smoking was an independent predictor of the composite endpoint of death/MI/stroke (hazard ratio HR: 1.8; 95% confidence interval CI: 1.3 to 2.5; p = 0.001) and MACCE (HR: 1.4; 95% CI: 1.1 to 1.7; p = 0.02). Conclusions Smoking is associated with poor clinical outcomes after revascularization in patients with complex CAD. This places further emphasis on efforts at smoking cessation to improve revascularization benefits. (SYNTAX Study: TAXUS Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries; NCT00114972 )
Background Patients diagnosed with bile-duct, pancreatic-head, and ampullary carcinomas have a poor prognosis. Objective This study evaluated the potential curative efficacy and safety of ...intraluminal brachytherapy by using radioactive stents for palliative treatment of these patients. Design and Setting Patients with inoperable extrahepatic bile-duct (n = 2), pancreatic-head (n = 6), or ampullary (n = 3) carcinomas were treated by intraluminal implantation of radioactive stents designed according to a computerized treatment-planning system. Interventions Both radioactive stents and commonly used self-expanding metallic or plastic stents were placed in the common bile duct (CBD) of the patients. For pancreatic carcinoma, the combination of radioactive CBD and pancreatic duct (PD) stents or only a radioactive PD stent was chosen according to the tumor position. Main Outcome Measurements Survival, tumor status, and complications were assessed during the follow-up period. Results A total of 16 radioactive stents were successively placed in all 11 patients. There were no life-threatening complications. The median survival was 150 days. After 2 months of the placement of radioactive stents, 8 patients (72.7%) had stable disease, whereas 3 patients (27.3%) showed progressive disease. Conclusions The combination of radioactive stents and metallic and/or plastic stents was technically feasible and tolerable in patients with advanced tumors around the pancreatic-head area.
Background Stress responses have been studied extensively in animal models, but effects of major life stress on the human brain remain poorly understood. The aim of this study was to determine ...whether survivors of a major earthquake, who were presumed to have experienced extreme emotional stress during the disaster, demonstrate differences in brain anatomy relative to individuals who have not experienced such stressors. Methods Healthy survivors living in an area devastated by a major earthquake and matched healthy controls underwent 3-dimentional high-resolution magnetic resonance imaging (MRI). Survivors were scanned 13–25 days after the earthquake; controls had undergone MRI for other studies not long before the earthquake. We used optimized voxel-based morphometry analysis to identify regional differences of grey matter volume between the survivors and controls. Results We included 44 survivors (17 female, mean age 37 standard deviation (SD) 10.6 yr) and 38 controls (14 female, mean age 35.3 SD 11.2 yr) in our analysis. Compared with controls, the survivors showed significantly lower grey matter volume in the bilateral insula, hippocampus, left caudate and putamen, and greater grey matter volume in the bilateral orbitofrontal cortex and the parietal lobe (all p < 0.05, corrected for multiple comparison). Limitations Differences in the variance of survivor and control data could impact study findings. Conclusion Acute anatomic alterations could be observed in earthquake survivors in brain regions where functional alterations after stress have been described. Anatomic changes in the present study were observed earlier than previously reported and were seen in prefrontal–limbic, parietal and striatal brain systems. Together with the results of previous functional imaging studies, our observations suggest a complex pattern of human brain response to major life stress affecting brain systems that modulate and respond to heightened affective arousal.
Objectives This study aimed to update the Logistic Clinical SYNTAX score to predict 3-year survival after percutaneous coronary intervention (PCI) and compare the performance with the SYNTAX score ...alone. Background The SYNTAX score is a well-established angiographic tool to predict long-term outcomes after PCI. The Logistic Clinical SYNTAX score, developed by combining clinical variables with the anatomic SYNTAX score, has been shown to perform better than the SYNTAX score alone in predicting 1-year outcomes after PCI. However, the ability of this score to predict long-term survival is unknown. Methods Patient-level data (N = 6,304, 399 deaths within 3 years) from 7 contemporary PCI trials were analyzed. We revised the overall risk and the predictor effects in the core model (SYNTAX score, age, creatinine clearance, and left ventricular ejection fraction) using Cox regression analysis to predict mortality at 3 years. We also updated the extended model by combining the core model with additional independent predictors of 3-year mortality (i.e., diabetes mellitus, peripheral vascular disease, and body mass index). Results The revised Logistic Clinical SYNTAX models showed better discriminative ability than the anatomic SYNTAX score for the prediction of 3-year mortality after PCI (c-index: SYNTAX score, 0.61; core model, 0.71; and extended model, 0.73 in a cross-validation procedure). The extended model in particular performed better in differentiating low- and intermediate-risk groups. Conclusions Risk scores combining clinical characteristics with the anatomic SYNTAX score substantially better predict 3-year mortality than the SYNTAX score alone and should be used for long-term risk stratification of patients undergoing PCI.
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