Somatic BrafV600E mutation in the cerebral endothelium induces brain arteriovenous malformations.

Current treatments of brain arteriovenous malformation (BAVM) are associated with considerable risks and at times incomplete efficacy. Therefore, a clinically consistent animal model of BAVM is urgently needed to investigate its underlying biological mechanisms and develop innovative treatment strategies. Notably, existing mouse models have limited utility due to heterogenous and untypical phenotypes of AVM lesions. Here we developed a novel mouse model of sporadic BAVM that is consistent with clinical manifestations in humans. Mice with BrafV600E mutations in brain ECs developed BAVM closely resembled that of human lesions. This strategy successfully induced BAVMs in mice across different age groups and within various brain regions. Pathological features of BAVM were primarily dilated blood vessels with reduced vascular wall stability, accompanied by spontaneous hemorrhage and neuroinflammation. Single-cell sequencing revealed differentially expressed genes that were related to the cytoskeleton, cell motility, and intercellular junctions. Early administration of Dabrafenib was found to be effective in slowing the progression of BAVMs; however, its efficacy in treating established BAVM lesions remained uncertain. Taken together, our proposed approach successfully induced BAVM that closely resembled human BAVM lesions in mice, rendering the model suitable for investigating the pathogenesis of BAVM and assessing potential therapeutic strategies.

Correlation exploration among CT imaging, pathology and genotype of pulmonary ground-glass opacity.

To analyse the clinical features, imaging manifestation, pathological typing and genetic testing results of patients undergoing surgery for ground-glass opacity (GGO) nodules, and explore the reasonable diagnosis and treatment program for GGO patients as to provide the basis for the establishment of GGO treatment process. This study is an exploratory study. 465 cases with GGO confirmed by HRCT, undergoing surgery and approved by pathologic diagnosis in Shanghai pulmonary hospital were enrolled in this study. All the patients with GGO were cases with single lesion. The relationship between the clinical, imaging, pathological and molecular biological data of single GGO were statistically studied. (1) Among 465 cases, the median age was 58 years and females were 315 (67.7%); there were 397 (85.4%) non-smoking, and 354 cases (76.1%) had no clinical symptoms. There were 33 cases of benign and 432 cases of malignant GGO. Significant differences were observed on the size, vacuole sign, pleural indentation and blood vessel sign of GGO between two groups (p < 0.05). Of 230 mGGO, there were no AAH, 13 cases of AIS, 25 cases of MIA and 173 cases of invasive adenocarcinoma. The probability of solid nodules in invasive adenocarcinoma was higher than that in micro invasive carcinoma, and the difference was statistically significant (p < 0.05). 360 cases were followed up with the average follow-up time of 6.05 months, and GGO of 34 cases (9.4%) increased. (2) In 428 adenocarcinoma samples approved by pathologic diagnosis, there were 262 (61.2%) lesions of EGFR mutation, 14 (3.3%) lesions of KRAS mutation, 1 (0.2%) lesion of Braf mutation, 9 (2.1%) lesions of EML4-ALK gene fusion and 2 (0.5%) lesions of ROS1 fusion. The detection rate of gene mutation in mGGO was higher than that of pGGO. During the follow-up period, genetic testing results of 32 GGO showed that EGFR mutation rate was 53.1%, ALK positive rate of 6.3%, KRAS mutation rate of 3.1% and no ros1 and BRAF gene mutation. No statistically significant difference was observed in comparison with unchanged GGO. (3) EGFR mutation rate of invasive adenocarcinoma was the highest (168/228, 73.7%), mainly in the 19Del and L858R point mutations. No KRAS mutation was found in atypical adenoma hyperplasia. No significant difference was observed on the mutation rate of KRAS between different types of GGO (p = 0.811). EML4-ALK fusion gene was mainly detected in invasive adenocarcinoma (7/9). GGO tends to occur in young, non-smoking women. The size of GGO is related to the degree of malignancy. Pleural depression sign, vacuole sign and vascular cluster sign are all characteristic images of malignant GGO. pGGO and mGGO reflect the pathological development of GGO. During the follow-up, it is found that GGO increases and solid components appear, which is the indication of surgical resection. The detection rate of EGFR mutations in mGGO and invasive adenocarcinoma is high. pGGO has heterogeneity in imaging, pathology and molecular biology. Heterogeneity research helps to formulate correct individualized diagnosis and treatment plans.

Clinical features and outcomes of perimedullary arteriovenous fistulas: comparison between micro- and macro-type lesions.

BACKGROUND: Although the angioarchitecture of perimedullary arteriovenous fistulas (PMAVFs) is straightforward, their size and blood flow are highly heterogeneous. This study aimed to evaluate the differences in clinical features and outcomes of PMAVFs based on lesion size and blood flow. METHODS: 114 consecutive patients with PMAVFs from two institutes were retrospectively reviewed. The lesions were classified as either micro-PMAVFs (shunt point diameter <1 cm) or macro-PMAVFs (shunt point diameter ≥1 cm). RESULTS: The patients with micro-PMAVFs were older at the first presentation (33.50 vs 13.50 years, p<0.001). Macro-PMAVFs were more commonly associated with spinal metameric arteriovenous shunts (6.9% vs 28.6%, p=0.003). Compared with the macro-PMAVFs, the micro-PMAVFs showed a significantly higher risk of gradual clinical deterioration after initial onset (73.6%/year vs 10.0%/year; HR 3.888, 95% CI 1.802 to 8.390, p=0.001). A total of 58.6% of the micro-PMAVFs were treated surgically, whereas 85.7% of the macro-PMAVFs were treated via endovascular approaches. Complete obliteration was 73.7% for the whole cohort, and was more common for the micro-PMAVFs than for the macro-PMAVFs (87.9% vs 58.9%, p=0.001). At the last follow-up, spinal function was significantly improved compared with the pretreatment status, and the rate of severe disability of patients with macro-PMAVFs was slightly but not significantly higher than that of patients with micro-PMAVFs (16.1% vs 8.6%, p=0.315) CONCLUSIONS: The clinical risks, treatment strategies and obliteration rates of PMAVFs differ based on their size and blood flow.

Comparison of drug-eluting stents and coronary artery bypass surgery for the treatment of multivessel coronary disease: three-year follow-up results from a single institution.

BACKGROUND: Numerous studies have compared the outcomes of coronary artery bypass grafting (CABG) surgery and coronary stenting for the treatment of multivessel coronary disease. In 2003, drug-eluting stents were introduced with the hope of reducing restenosis. However, limited information exists on the comparison of drug-eluting stents and CABG surgery. The long-term outcome of drug-eluting stents compared with that of CABG surgery is also unclear. METHODS AND RESULTS: We identified 3720 consecutive patients with multivessel disease who underwent isolated CABG surgery or received drug-eluting stents between April 1, 2004, and December 31, 2005, and we compared safety (total mortality, myocardial infarction, and stroke) and efficacy (target-vessel revascularization) during a 3-year follow-up. These outcomes were compared after adjustment for differences in baseline risk factors. Patients who underwent CABG (n=1886) were older and had more comorbidities than patients who received drug-eluting stents (n=1834). Patients receiving drug-eluting stents had considerably higher 3-year rates of target-vessel revascularization. Drug-eluting stents were also associated with higher rates of death (adjusted hazard ratio, 1.62; 95% confidence interval, 1.07 to 2.47) and myocardial infarction (adjusted hazard ratio, 1.65; 95% confidence interval, 1.15 to 2.44). The risk adjusted rate of stroke was similar in the 2 groups (hazard ratio, 0.92; 95% confidence interval, 0.69 to 1.51). CONCLUSIONS: In a cohort of patients with multivessel disease, CABG was associated with lower rates of death, myocardial infarction, and target-vessel revascularization than drug-eluting stents.

Commonality of functional annotation: a method for prioritization of candidate genes from genome-wide linkage studies.

Linkage studies of complex traits frequently yield multiple linkage regions covering hundreds of genes. Testing each candidate gene from every region is prohibitively expensive and computational methods that simplify this process would benefit genetic research. We present a new method based on commonality of functional annotation (CFA) that aids dissection of complex traits for which multiple causal genes act in a single pathway or process. CFA works by testing individual Gene Ontology (GO) terms for enrichment among candidate gene pools, performs multiple hypothesis testing adjustment using an estimate of independent tests based on correlation of GO terms, and then scores and ranks genes annotated with significantly-enriched terms based on the number of quantitative trait loci regions in which genes bearing those annotations appear. We evaluate CFA using simulated linkage data and show that CFA has good power despite being conservative. We apply CFA to published linkage studies investigating age-of-onset of Alzheimer's disease and body mass index and obtain previously known and new candidate genes. CFA provides a new tool for studies in which causal genes are expected to participate in a common pathway or process and can easily be extended to utilize annotation schemes in addition to the GO.

MicroRNA: novel regulators involved in the remodeling and reverse remodeling of the heart.

BACKGROUND: MicroRNAs (miRNAs) may serve as potential diagnostic biomarkers and therapeutic targets in cardiovascular research. However, the association between miRNAs and heart remodeling/reverse remodeling has not been evaluated. METHODS: Lewis rats were divided into three groups: control animals, animals subjected to abdominal aortic constriction (AAC) and those with heterotopic transplantation of abdominal aortic constriction (AAC-HT), respectively. The cardiomyocyte cross-sectional area and changes in the heart cavity were determined. miRNA microarray was used to search for changes in miRNAs during hypertrophy and in the unloading heart, which was also verified using real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). RESULTS: The AAC-HT group exhibited a 54% decrease in the cardiomyocyte cross-sectional area compared to the AAC group. In the two test groups, miRNA microarrays revealed changes in 293 miRNAs, among which 40 miRNAs changed >2-fold. Some major changes were also confirmed using qRT-PCR primers. The results indicated that changes in miR-23a and miR-29a were most significant, thus suggesting that these miRNAs may play important roles in heart remodeling and reverse remodeling. CONCLUSIONS: The changes observed in miRNA expression during hypertrophy and reverse remodeling may indicate possibly meaningful targets for regulating the remodeling or reverse remodeling of the heart.

Correction of diffusion calculations when using two types of non-rectangular simulation boxes in molecular simulations.

Although simulation boxes used in molecular dynamics are normally chosen to be cubic or rectangular, two other cell shapes that are very familiar to crystallographers-the truncated octahedron and the rhombic dodecahedron-could also be used because they are also space-filling cells. Due to their spherical nature, these boxes have been intentionally applied in simulations of biomolecular solutions and liquid structures. Indeed, due to the advantages of running many molecular dynamic codes in parallel, simulations based on these non-rectangular boxes have been growing in popularity in recent years. In this work, the effects of using these two types of boxes on diffusion are explored for the first time, and an appropriate correction formula is derived theoretically within the framework of hydrodynamics. In addition, the range of validity for the correction formula is evaluated by performing molecular dynamic simulations on argon at three different densities.

[Effect of proteins pre-coating on bone marrow mesenchymal cells retention and proliferation on decellular bovine pericardium].

To observe the growth of rat bone marrow mesenchymal cells (BMMCs) on decellular bovine pericardia in vitro and to investigate the effect of proteins pre-coating on cells retention and proliferation, bovine pericardia were decellularized using trypsin, DNase and Triton X-100 respectively. Then three proteins (fibronetin (FN), gelatin, collagen I) were coated on the surfaces of the bovine pericardia separately. BMMCs were harvested from rat thighbone marrow , then expanded and seeded onto decellular bovine pericardia with the proteins pre-coated . Decelluar bovine pericardia without coating were used as controls. The retention and growth of BMMSCs were observed by Hochest staining and analyzed by MTT method. It was shown that the retention and proliferation of BMMCs on FN group and gelatin group were significantly enhanced comparing with those on collagen I group and control group (P < 0.001). There was no significant difference between FN group and gelatin group (P > 0.05), nor between collagen I group and control group (P > 0.05). We conclude that the retention and proliferation of seeding cells on FN and gelatin could be significantly improved on decellular bovine pericardia (DBP) but not on collagen I.

Social hierarchy modulates responses of fish exposed to contaminants of emerging concern.

Many organisms, including the fathead minnow (Pimephales promelas), a toxicological model organism, establish social hierarchies. The social rank of each male in a population is under the control of the hypothalamic-pituitary-gonadal (HPG) axis mainly through regulation of circulating androgen concentrations, which in turn drive the expression of secondary sex characteristics (SSCs). As dominant and subordinate males in an exposure study are initially under different physiological conditions (i.e., differing plasma androgen concentrations), we proposed that they belong to different subpopulations in the context of exposure to compounds that may interact with the HPG axis. Using a meta-analysis of our data from several previously published studies, we corroborated the hypothesis that social status, as indicated by SSCs, results in distinct clusters (eigenvalues >0.8 explaining >80% of variability) with differential expression of plasma vitellogenin, a commonly used biomarker of exposure to contaminants of emerging concern (CEC). Furthermore, we confirmed our predictions that exposure to estrogenic CECs would homogenize plasma vitellogenin response (E1: cluster mean SSC values decreased to 4.33 and 4.86 relative to those of control; E2: decreased to 4.8 and 5.37) across the social hierarchy. In contrast, serotonin-specific reuptake inhibitors expand this response range (cluster mean SSC increased to 5.21 and 6.5 relative to those of control). Our results demonstrated that social hierarchies in male fathead minnows result in heterogeneous responses to chemical exposure. These results represent a cautionary note for the experimental design of single-sex exposure studies. We anticipate our study to be a starting point for the re-evaluation of toxicological data analyses in single sex exposure experiments.

Influence of diabetes mellitus on long-term clinical and economic outcomes after coronary artery bypass grafting.

BACKGROUND: China has the most patients with diabetes mellitus (DM) in the world and, annually, approximately 1 million Chinese become diabetic. We investigated both clinical and economic outcomes in a large Chinese cohort of diabetic patients undergoing coronary artery bypass graft surgery (CABG). METHODS: All 9,240 consecutive patients who underwent isolated, primary, elective CABG between January 1999 and December 2008 were included and analyzed for long-term major adverse cardiovascular and cerebrovascular events and economic outcomes up to 2 years after the procedure. The DM patients were divided into DM subgroups controlled by diet (n = 375), medication (n = 1,826) or insulin (n = 481). RESULTS: During the study period, the proportion of patients undergoing CABG who have DM increased from 20.1% to 31.8% in China. None of the DM subgroups was independently associated with in-hospital death, but DM was an independent predictor for long-term major adverse cardiovascular and cerebrovascular events (hazard ratio 1.29, 95% confidence interval: 1.14 to 1.46). Medically controlled DM and insulin-dependent DM, but not diet-controlled DM were independent predictors of long-term outcomes after CABG. Cost for initial hospitalization was higher for DM patients (76,782 Ren Min Bi [RMB] versus 65,521 RMB, respectively; p < 0.001). At 2 years after CABG, costs for DM patients were 11,261 RMB (approximately US $1,623) higher than for non-DM patients (p < 0.001). CONCLUSIONS: CABG for patients with DM was significantly more expensive and was associated with worse long-term outcomes compared with non-DM patients. The rising incidence of DM, combined with the significant incremental costs represents significant clinical, economic, and social challenges for the Chinese healthcare system.

Impaired myocardium energetics associated with the risk for new-onset atrial fibrillation after isolated coronary artery bypass graft surgery.

BACKGROUND: New-onset postoperative atrial fibrillation (POAF) is one of the most common complications occurring in 10-40% of patients after coronary artery bypass graft (CABG) surgery. Recent studies suggest that dysmetabolism may contribute to the pathogenesis of atrial fibrillation; however, the putative mechanism in patients undergoing CABG surgery is unknown. Peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) has been demonstrated as a master regulator of myocardial energy metabolism, and glucose transporter 3 (GLUT3) has both a higher affinity for glucose and a much greater transport capacity compared with GLUT1, GLUT2, and GLUT4. We sought to evaluate the role of energy metabolism, especially the glucose metabolism, on patients after isolated CABG surgery. METHODS AND RESULTS: Right atrial appendages were obtained from 79 patients who were in normal sinus rhythm and undergoing isolated CABG; those who exhibited new-onset POAF (n=22) or remained in sinus rhythm (n=57) were prospectively matched on the basis of preoperative, intraoperative, and postoperative characteristics. POAF was assessed by electrocardiogram and must have required the initiation of antiarrhythmic therapy or anticoagulation. Local PGC-1α and GLUT3 concentrations were quantified by enzyme-linked immunosorbent assay in tissue homogenates. The comparison of mRNA expression was tested by quantitative real-time PCR. PGC-1α and GLUT3 levels and the related protein mRNA expression were significantly reduced in POAF patients compared with controls (P<0.05). This selective reduction in PGC-1α was associated with the presence of diabetes mellitus (P<0.05). CONCLUSION: Patients who have low PGC-1α and GLUT3 levels are at increased risk for new-onset POAF. The myofibrillar energetic impairment may be important in the pathogenesis of atrial fibrillation.

Accurate and flexible power calculations on the spot: Applications to genomic research.

Often investigators need to calculate power to demonstrate feasibility of proposed genetic studies for grant proposals or simply to aid in their own study planning. Frequently, power can be easily calculated using a closed form formula. However, in some situations such formulae for calculating power have not been derived and derivation on demand may be difficult if not impossible. In these situations investigators typically perform simulations specific to the study. Yet such simulations can be computationally extensive and take weeks to months depending on the circumstances. Here, we provide a simple method to rapidly estimate power when one has power estimates available for corresponding situations that differ from the situation of interest only in sample size and/or alpha (type I error) level desired. We show by application to multiple published results from the genomics field that these methods are generally very accurate and applicable to a broad range of genomic studies.

Signal pathways involved in reverse remodeling of the hypertrophic rat heart after pressure unloading.

BACKGROUND: The purpose of this study was to gain a better understanding of molecular changes associated with the beneficial reverse remodeling through heterotopic transplantation model of rat hypertrophic hearts. METHODS: Stable cardiac hypertrophy was induced by abdominal aortic constriction (AAC) in Lewis rats (6 weeks). Left ventricular (LV) pressure unloading was induced by heterotopic transplantation of hypertrophic hearts (AAC-HT) (2 weeks). We measured heart weight (HW), LV weight (LVW) and the LV-to-final body weight ratio (LVW/BW). Cross-sectional areas of cardiomyocyte and collagen content were assessed by hematoxylin/eosin staining and picrosirius red staining, respectively. We further analyzed the signaling pathways of mitogen-activated protein kinases (MAPKs), Akt/GSK3ß, NF-κB, metalloproteinase-2,9 (MMP-2, 9) and tissue inhibitors of metalloproteinase-1 (TIMP-1) by Western blot. RESULTS: The HW, LVW and LVW/BW in AAC hearts were higher than normal hearts, but the transplanted hearts showed a significant reduction in HW, LVW and LVW/BW compared to AAC hearts. Unloading induced a decrease in cardiomyocyte size and an increase in collagen content in AAC-HT hearts. A significant decrease in phosphorylation of p44/p42 MAP kinases (ERK), Akt, GSK3ß and NF-κB was detected in AAC-HT hearts, but the phosphorylation of p38 MAP kinase and Jun-N-terminal kinase (JNK) was not changed. MMP-2, MMP-9 and TIMP-1 activity also increased accompanied by unloading. CONCLUSIONS: Pressure unloading of the hypertrophic heart caused a reverse remodeling through regulating the ERK, Akt/GSK3ß, and NFκB signal pathways, revealing these as potential target pathways for reversal of LV hypertrophy.

Effects of aprotinin on short-term and long-term outcomes after coronary artery bypass grafting surgery.

BACKGROUND: Recent studies demonstrated that aprotinin use would increase the short-term and long-term mortality and complications after coronary artery bypass grafting (CABG). This study was to investigate effects of aprotinin during isolated primary CABG on short-term and long-term outcomes in Chinese patients. METHODS: We studied 5,103 consecutive Chinese patients who underwent isolated primary CABG from 1999 to 2005. Of all the patients, 4,122 received aprotinin during operation (aprotinin group) and 981 received no aprotinin or other antifibrinolytic therapy (control group). Short-term and long-term mortality and major complications were analyzed with multivariate regression analysis. Propensity adjustment method was used to minimize the selection bias between the two groups, and propensity matching method was used to yield two well-matched groups for further comparison. RESULTS: Blood loss after operation was significantly reduced in the aprotinin group compared with the control group (p < 0.001). Aprotinin use was neither associated with the perioperative mortality (p = 0.45, relative risk, 1.34) or major complications, nor was it associated with long-term mortality (p = 0.21, relative risk, 1.26) and major adverse cardiac and cerebrovascular events (p = 0.82, relative risk, 0.98). After propensity adjustment for the baseline characteristics, we obtained similar results. In addition, comparison between the two well-matched groups showed no significant difference either in baseline characteristics or in short-term and long-term outcomes. CONCLUSIONS: Aprotinin use during isolated primary CABG reduced blood loss significantly, but was not associated with short-term or long-term mortality and complications. Aprotinin use in relatively low-risk CABG patients was effective and safe in a Chinese (Asian) population.

Left ventricular reconstruction with no-patch technique: early and late clinical outcomes.

BACKGROUND: Few studies have evaluated late clinical outcome of no-patch technique in patients with large left ventricular aneurysms. The objectives of this study were to evaluate a no-patch surgical technique to reconstruct the left ventricle in patients with left ventricular aneurysm and to assess early and late clinical outcomes. METHODS: In 1995, we began using a no-patch technique in patients with dyskinetic left ventricular aneurysms. A total of 145 patients underwent left ventricular reconstruction with this technique and were followed up for (59 ± 29) months (range, 1 - 127 months). Risk factors for early mortality were analyzed by bivariate analyses. Cox's proportional hazards model was used to calculate risk factors for all-cause mortality and hospital readmission. Kaplan-Meier methodology was used to analyze late survival. RESULTS: One week after operation, left ventricular end-diastolic diameter had decreased from (61 ± 8) mm to (55 ± 8) mm, and geometry of the left ventricle was restored to a more normal conical shape. Early mortality was 3% and late mortality 11%. Over a 5-year follow-up period, hospital readmission was 28%. One-, 5-, and 10-year survival estimates were 95% (95% confidence interval (CI) 91% - 99%), 86% (95%CI 78% - 94%), and 74% (95%CI 60% - 88%). Readmission-free survival at 1 and 5 years after operation was 87% (95%CI 81% - 93%) and 60% (95%CI 50% - 70%), respectively. CONCLUSION: The no-patch technique for left ventricular reconstruction is an effective and simple procedure that can achieve satisfactory early and late clinical outcomes in patients with left ventricular aneurysms.

The Chinese coronary artery bypass grafting registry study: how well does the EuroSCORE predict operative risk for Chinese population?

OBJECTIVE: The European System for Cardiac Operative Risk Evaluation (EuroSCORE) model is a widely used risk prediction algorithm for cardiac surgery in China due to lack of a local model, although its validation has never been tested. The aim of this study was to assess the performance of the logistic EuroSCORE when applied in the Chinese Coronary Artery Bypass Grafting Registry database, which is representative of adult cardiac surgery in China. METHODS: The logistic EuroSCORE model was applied to all patients undergoing coronary artery bypass grafting (CABG) surgery at 35 centres in China between January 2004 and December 2005. The entire cohort and a subgroup of patients undergoing isolated CABG were analysed. The calibration of the EuroSCORE model was assessed by comparing observed and predicted in-hospital mortalities. Discrimination was tested by determining the area under the receiver operating characteristic (ROC) curve. RESULTS: The Chinese CABG Registry Study recruited 9248 patients. There were significant differences in the prevalence of risk factors between the Chinese population and European cardiac surgical populations. For the entire cohort, the predicted mortality was 5.51% and observed mortality was 3.27%. Of the isolated CABG subset of 8120 patients, the predicted mortality was 4.21% and the observed mortality was 2.22%. The logistic EuroSCORE overpredicted observed mortality for the entire cohort and the isolated CABG subset at all risk tertiles to different degrees. The discriminative power of EuroSCORE was acceptable but not very satisfactory, with an area under the ROC curve of 0.72 for the entire cohort and 0.71 for the isolated CABG subset. CONCLUSION: EuroSCORE model does not accurately predict outcomes in this group of Chinese CABG patients. Therefore, caution should be exercised when using it for risk prediction in China. Creation of a new model, which accurately predicts outcomes in Chinese CABG patients, is warranted.

Impact of off-pump techniques on sex differences in early and late outcomes after isolated coronary artery bypass grafts.

BACKGROUND: Off-pump coronary artery bypass graft surgery (OPCAB) is associated with lower early mortality and benefits women disproportionately. The objective of this study was to assess the impact of off-pump techniques on sex differences in late outcomes. METHODS: We reviewed a clinical database of consecutive patients who underwent isolated coronary artery bypass graft surgery (CABG) at FuWai Hospital from 1999 to 2005. Logistic regression analysis and proportional hazards modeling were used to investigate whether sex or surgery type were associated with early mortality and late outcomes (mortality, major cardiac and cerebral event). RESULTS: Female sex was associated with higher rates of early death (adjusted odds ratio, 4.726; p < 0.0001), and OPCAB benefited women disproportionately for early mortality. Odds ratio of death for women versus men was 4.726 (p < 0.0001) in the conventional CABG on cardiopulmonary bypass group; odds ratio of death for women versus men was 1.344 (p = 0.5617) in the OPCAB group. Analysis of late outcomes indicated that OPCAB and cardiopulmonary bypass resulted in similar survival, regardless of sex. The women versus men hazard ratio of late mortality after CABG on cardiopulmonary bypass and OPCAB for women was 0.851 (p = 0.4984) and 0.650 (p = 0.2005), respectively. Women treated with OPCAB were less likely to be free from major cardiac and cerebral events than men treated with OPCAB. The women versus men hazard ratio of major cardiac and cerebral events after CABG on cardiopulmonary bypass and OPCAB for women was 1.079 (p = 0.4992) and 1.299 (p = 0.0387), respectively. CONCLUSIONS: Compared with men, women are a high-risk group and benefit from off-pump operation in terms of early mortality after CABG. Conversely, during follow-up, women have high adjusted risks of major cardiac and cerebral events after OPCAB.

Surgery of left ventricular aneurysm: a propensity score-matched study of outcomes following different repair techniques.

To evaluate early and late outcomes of modified left ventricular reconstruction (VR) and linear repair (LR) of post-infarct left ventricular aneurysm (LVA). A total of 514 patients were consecutively operated on for LVA with modified VR technique in 145 and LR in 352 patients. Using the propensity score-matching method, we selected 202 patients (101 LRs vs. 101 VRs) with similar pre- and intra-operative characteristics and compared their clinical outcomes. After matching, the two groups of patients were similar with regard to baseline data. The increment of left ventricular ejection fraction (LVEF) in VR group was more significant than that in LR group. Operative mortality was 2.0% (2.0% LRs vs. 2.0% VRs, P=NS). There was a statistically significant difference between LR and VR patients in MACCEs (29.7% LRs vs. 13.9% VRs, P<0.01) and hospital readmissions (51.5% LRs vs. 30.7% VRs, P<0.01). Overall long-term mortality and cardiac mortality were the same between the two groups (mortality: 11.9% LRs vs. 11.9% VRs, P=NS; cardiac mortality: 9.9% LRs vs. 7.9% VRs, P=NS). The technique of repairing LVA did not affect the early and later mortality.

A comparison before and after aprotinin was suspended in cardiac surgery: different results in the real world from a single cardiac center in China.

OBJECTIVE: Use of aprotinin has been suspended in cardiac surgery since recent studies reported its risks associated with mortality and other adverse events. This study was to investigate the safety and efficacy of aprotinin through a comparison before and after aprotinin was suspended in cardiac surgery. METHODS: We designed a case-control study in two groups of patients who underwent cardiac surgery just before and after aprotinin was suspended in China. The aprotinin group (n = 1699) was defined as operations performed from June 19, 2007, to December 18, 2007, when aprotinin was used in all the patients. The control group (n = 2225) was defined as operations performed from December 19, 2007, to June 18, 2008, when aprotinin was not used. We compared early postoperative outcomes between the two groups. RESULTS: The aprotinin group had less postoperative blood loss, transfusion requirement, and reoperation for bleeding. Application of aprotinin did not increase the risk of in-hospital mortality (0.5% vs 1.0%; P = .08) and other major adverse outcome events, including renal, cardiac, neurologic, and pulmonary complications. The aprotinin group had a shorter mechanical ventilation time (P = .04), a lower rate of delayed mechanical ventilation time (P = .04), and a higher arterial oxygen tension/inspired oxygen fraction ratio in arterial blood gas analysis (P < .001). Multivariable logistic regression analysis confirmed findings from univariate analysis. After propensity adjustment for the baseline characteristics, we obtained similar results. CONCLUSIONS: Use of aprotinin in cardiac surgery could reduce blood loss and transfusion requirement significantly and showed a protective effect on the lungs, but it did not increase the risk of mortality or major complications.

Impact of renal dysfunction on long-term survival after isolated coronary artery bypass surgery.

BACKGROUND: Preoperative renal dysfunction has been an important predictor for adverse cardiovascular events after coronary artery bypass grafting (CABG). In the past, serum creatinine was widely used to assess renal function. Until recently, estimated glomerular filtration rate (eGFR) was recommended in evaluating renal function. The Cockcroft-Gault formula and the Modification of Diet in Renal Disease (MDRD) equation are two widely used formulas in clinical practice. Which method best predicts long-term outcome after CABG is still unknown. This study compared the predictive effectiveness of the Cockcroft-Gault formula, the MDRD equation, and serum creatinine level for in-hospital and long-term mortality. METHODS: We retrospectively reviewed data collected from 5559 patients who underwent isolated CABG at Fuwai Hospital from January 1999 to December 2005. The main outcomes were in-hospital and long-term mortality. Receiver operating characteristic (ROC) curves and Cox analysis were used for the comparison. RESULTS: Mean follow-up was 56.5 +/- 24.6 months. ROC curve analysis showed that the Cockcroft-Gault formula had the greatest accuracy for predicting in-hospital mortality (area under the curve, 0.755; p < 0.001). Multivariate analysis confirmed that the eGFR based on the Cockcroft-Gault formula was an independent predictor of in-hospital (odds ratio, 4.51, p < 0.001) and long-term (hazard ratio, 1.54; p = 0.003) mortality. Both formulas were better than the serum creatinine level. CONCLUSIONS: Both formulas could provide a better measure of risk assessment than serum creatinine for in-hospital and long-term mortality. The Cockcroft-Gault formula was better than the MDRD equation for predicting in-hospital mortality.