Supplementing maternal diet with milk oligosaccharides and probiotics helps develop the immune system and intestinal flora of offsprings.

Intestinal flora is very important for improving the development of the immune system in newborns. Maternal diet during pregnancy and lactation is one of the key factors affecting the growth and development of offspring. The objective of the present study was to examine whether supplementation of maternal diet with milk oligosaccharides and Bifidobacterium could influence the development of the intestinal flora and immune system of neonatal mice. In total, 30 pregnant Institute of Cancer Research (ICR) mice were randomly divided into six groups: a control group (basal diet) and five intervention groups (basal diet supplemented with different doses of 2'-fucosyllactose [2'-FL] and Bifidobacterium Bb12) during the pregnancy period. All female mice were monitored for physical health during gavage. After delivery, the number of mice in each litter, any deformity, and the development of the offspring were recorded. The spleen, blood, and fecal samples of six groups of 10-12 day-old offspring were collected. The results demonstrated that maternal milk oligosaccharides and probiotics conferred protective effects against lipopolysaccharide (LPS)-induced immunosuppression in mice offspring by significantly enhancing the immune organ indexes, splenocyte proliferation, immunoglobulin (immunoglobulin G, A, M) production as well as improving the macrophage phagocytosis (p < .05). The abundance of Lactobacilli and Bifidobacteria in the feces of offspring mice in the intervention groups was significantly higher than that of the offspring mice in the control group (p < .05). These findings suggest that the combination of 2'-FL and Bifidobacterium Bb12 displayed synergistic interactions between the two components that could promote the development of the immune system of the offsprings and improve their microbiota through maternal ingestion.

Recent Advances in Genetic Code Expansion Techniques for Protein Phosphorylation Studies.

Protein phosphorylation is a reversible, residue-specific posttranslational modification that plays a pivotal role in cell signaling, and the phosphorylation state of proteins is tightly regulated by kinases and phosphatases. Malfunction of this regulation is often associated with human diseases, and therefore elucidation of the function and regulation of this posttranslational modification is important. Genetic code expansion, which allows for site-specific introduction of noncanonical amino acids directly into target proteins in response to a non-sense codon is a powerful method for preparing homogeneously phosphorylated proteins both in Escherichia coli and mammalian cells and therefore is useful for studying protein phosphorylation. Herein, we summarize recent developments in the application of genetic code expansion for protein phosphorylation studies.

When Supramolecular Chemistry Meets Chemical Biology: New Strategies to Target Proteins through Host-Guest Interactions.

Supramolecular chemistry for targeting proteins is of great interest for the development of novel approaches to recognize, isolate and control proteins. Taking advantage of chemical biology approaches, such as genetic-code expansion and enzyme-mediated ligation, guest recognition elements can be built into proteins of interest, allowing supramolecular control of protein function and regulation. In this viewpoint article, we will discuss the methods, applications, limitations, and future perspectives of supramolecular chemistry for targeting proteins in a site-specific manner.

Long-term clinical outcomes in transradial versus transfemoral access for left main percutaneous coronary intervention.

OBJECTIVE: The present study compared 10-year clinical outcomes between transradial access (TRA) and transfemoral access (TFA) for left main (LM) percutaneous coronary intervention (PCI). BACKGROUND: There are limited data regarding the long-term safety and efficacy of TRA for LM PCI. METHODS: This retrospective study evaluated consecutive patients who underwent unprotected LM PCI between January 2004 and December 2008 at Fu Wai Hospital. The exclusion criteria were age of less than 18 years and presentation with acute myocardial infarction. The primary endpoint was major adverse cardiac or cerebrovascular events (MACCE), which was defined as a composite of all-cause death, myocardial infarction, stroke, and any revascularization at the 10-year follow-up. RESULTS: Among 913 eligible patients, TRA was used for 417 patients (45.7%) and TFA was used for 496 patients (54.3%). The 30-day clinical outcomes were similar between the two groups. Results from the 10-year follow-up revealed that MACCE occurred in 180 patients (46.7%) from the TRA group and in 239 patients (51.2%) from the TFA group (log-rank p = .3). The TRA and TFA groups also had low and comparable cumulative rates of all-cause death (14.6% vs. 17.3%, log-rank p = .56) and cardiac death (7.9% vs. 9.1%, log-rank p = .7). CONCLUSION: The present study revealed no significant differences in long-term clinical outcomes when TRA or TFA were used for LM PCI.

Long-Term Clinical Outcomes of Unprotected Left Main Percutaneous Coronary Intervention: A Large Single-Centre Experience.

AIMS: This study sought to report the 10-year clinical outcomes of patients who underwent unprotected left main (LM) percutaneous coronary intervention (PCI) in a large centre. METHODS AND RESULTS: A total of 913 consecutive patients who underwent unprotected LM PCI from January 2004 to December 2008 at Fu Wai Hospital were retrospectively analysed; the mean age was 60.0 ± 10.9 years, females accounted for 22% of patients, diabetes was present in 27.7% of patients, and an LM bifurcation lesion occurred in 82.9% of patients. During the median follow-up of 9.7 years, major adverse cardiac or cerebrovascular events (MACCEs) occurred in 25.6% (234) of patients, and the rates of all-cause death, myocardial infarction, and stroke were 14.9%, 11.0%, and 7.1%, respectively. Cardiac death occurred in only 7.9% of patients. The estimated event rate was 41.9% for death/myocardial infarction/any revascularization and 45.9% for death/MI/stroke/any revascularization. Definite/probable stent thrombosis occurred in 4.3% (39) of patients. According to the subgroup analysis, IVUS-guided PCI was associated with less long-term MACCEs. Further multivariate analysis identified that age and LVEF<40% were the only independent predictors for 10-year death. Age, LVEF<40%, creatinine clearance, and incomplete revascularization were independent predictors for death/MI, while a two-stent strategy, diabetes, a transradial approach, and the use of bare metal stents (BMSs) or first-generation drug-eluting stents (DESs) were not. CONCLUSIONS: Unprotected LM PCI in a large cohort of consecutive patients in a single large centre demonstrated favourable long-term outcomes up to 10 years even with the use of BMSs and first-generation of DESs.

A General Supramolecular Approach to Regulate Protein Functions by Cucurbit[7]uril and Unnatural Amino Acid Recognition.

Regulation of specific protein function is of great importance for both research and therapeutic development. Many small or large molecules have been developed to control specific protein function, but there is a lack of a universal approach to regulate the function of any given protein. We report a general host-guest molecular recognition approach involving modification of the protein functional surfaces with genetically encoded unnatural amino acids bearing guest side chains that can be specifically recognized by cucurbit[7]uril. Using two enzymes and a cytokine as models, we showed that the activity of proteins bearing unnatural amino acid could be turned off by host molecule binding, which blocked its functional binding surface. Protein activity can be switched back by treatment with a competitive guest molecule. Our approach provides a general tool for reversibly regulating protein function through molecular recognition and can be expected to be valuable for studying protein functions.

Efficient Selection Scheme for Incorporating Noncanonical Amino Acids Into Proteins in Saccharomyces cerevisiae.

With the advances in the field of expanded genetic code, the application of non-canonical amino acid (ncAA) is considered an effective strategy for protein engineering. However, cumbersome and complicated selection schemes limit the extensive application of this technology in Saccharomyces cerevisiae. To address this issue, a simplified selection scheme with confident results was developed and tested in this study. Based on a mutation library derived from Escherichia coli tyrosyl-tRNA synthetase (EcTyrRS), a logic gate in synthetic biology was used to optimize screening procedures. We found that an "and" gate was more suitable than an "or" gate for isolating aminoacyl-tRNA synthetase from S. cerevisiae. The successful incorporation of O-methyltyrosine (OMeY) proved the utility and efficiency of this new selection scheme. After a round of positive selection, several new OMeY-tRNA synthetase (OMeYRS) mutants were screened, and their incorporation efficiency was improved. Furthermore, we characterized the insertion of several tyrosine analogs into Herceptine Fab and discovered that OMeYRS and its mutants were polyspecific. One of these mutants showed an optimal performance to incorporate different ncAAs into recombinant proteins in S. cerevisiae; this mutant was cloned and transfected into mammalian cells, and the results proved its functionality in HEK293 cells. This study could expand the application of ncAA in S. cerevisiae to construct efficient yeast cell factories for producing natural and synthetic products.

Thermophilic Pyrrolysyl-tRNA Synthetase Mutants for Enhanced Mammalian Genetic Code Expansion.

Genetic code expansion (GCE) is a powerful technique for site-specific incorporation of noncanonical amino acids (ncAAs) into proteins in living cells, which is achieved through evolved aminoacyl-tRNA synthetase mutants. Stability is important for promoting enzyme evolution, and we found that many of the evolved synthetase mutants have reduced thermostabilities. In this study, we characterized two novel pyrrolysyl-tRNA synthetases (PylRSs) derived from thermophilic archaea: Methanosarcina thermophila (Mt) and Methanosarcina flavescens (Mf). Further study demonstrated that the wild-type PylRSs and several mutants were orthogonal and active in both Escherichia coli and mammalian cells and could thus be used for GCE. Compared with the commonly used M. barkeri PylRS, the wild-type thermophilic PylRSs displayed reduced GCE efficiency; however, some of the mutants, as well as some chimeras, outperformed their mesophilic counterparts in mammalian cell culture at 37 °C. Their better performance could at least partially be attributed to the fact that these thermophilic synthetases exhibit a threshold of enhanced stability against destabilizing mutations to accommodate structurally diverse substrate analogues. These were indicated by the higher melting temperatures (by 3-6 °C) and the higher expression levels that were typically observed for the MtPylRS and MfPylRS mutants relative to the Mb equivalents. Using histone H3 as an example, we demonstrated that one of the thermophilic synthetase mutants promoted the incorporation of multiple acetyl-lysine residues in mammalian cells. The enzymes developed in this study add to the PylRS toolbox and provide potentially better scaffolds for PylRS engineering and evolution, which will be necessary to meet the increasing demands for expanded substrate repertoire with better efficiency and specificity in mammalian systems.

An Orthogonal Tyrosyl-tRNA Synthetase/tRNA Pair from a Thermophilic Bacterium for an Expanded Eukaryotic Genetic Code.

The Escherichia coli-derived tyrosyl-tRNA synthetase was the first enzyme engineered for genetic code expansion in a eukaryotic system but can charge only a limited set of structurally simple noncanonical amino acids. In contrast, the thermophilic Methanocaldococcus jannaschii-derived tyrosyl-tRNA synthetase mutants, used in only a prokaryotic system, can charge a surprisingly large set of structurally diverse ncAAs, due to their remarkable structural ability to tolerate mutations. Inspired by this, we characterized a new class of tyrosyl-tRNA synthetase/tRNATyr pairs from thermophilic bacterium Geobacillus stearothermophilus, which is homologous to the E. coli tyrosyl-tRNA synthetase but with better thermostability. This new pair is both orthogonal in mammalian cells and in Saccharomyces cerevisiae for genetic code expansion and can charge a diverse set of ncAAs with a comparable cellular efficiency, better specificity, and lower background, as compared to those of its E. coli homologue. This thermostable enzyme provides an alternative scaffold for synthetase library screening or evolution to genetically encode more structurally complex ncAAs in eukaryotic cells.

Proteomic Identification of Protein Tyrosine Phosphatase and Substrate Interactions in Living Mammalian Cells by Genetic Encoding of Irreversible Enzyme Inhibitors.

Protein tyrosine phosphatases (PTPs) play critical roles in cell signaling pathways, but identification of unknown PTPs for a given substrate in live cells remain technically challenging. Here, we synthesized a series of tyrosine-based irreversible PTP inhibitors and characterized by site-specific encoding on substrate proteins in cells with an expanded genetic code. By fine-tuning the chemical reactivity, we identified optimal active amino acid probes to covalently cross-link a PTP and its substrate both in vitro and in mammalian cells. Using HER2 as an example, we provide first direct evidence of HER2 Y1023 and SHP2 cross-linking in situ in living human cells. Moreover, proteomic analysis using our approach identified PTP1B as a novel phosphatase for HER2 that specifically dephosphorylated pY1221 position, which may shed light on the puzzle of PTP1B's role in HER2 positive breast cancer. This novel method provides a useful tool for dissecting tyrosine phosphoregulation in living cells.

Effect of final kissing balloon dilatation after one-stent technique at left-main bifurcation: a single center data.

BACKGROUND: Whether final kissing balloon (FKB) dilatation after one-stent implantation at left-main (LM) bifurcation site remains unclear. Therefore, this large sample and long-term follow-up study comparatively assessed the impact of FKB in patients with unprotected LM disease treated with one-stent strategy. METHODS: Total 1528 consecutive patients underwent LM percutaneous coronary intervention in one center from January 2004 to December 2010 were enrolled; among them, 790 patients treated with one drug-eluting stent crossover LM to left anterior descending (LAD) with FKB (n = 230) or no FKB (n = 560) were comparatively analyzed. Primary outcome was the rate of major adverse cardiovascular events, defined as a composite of death, myocardial infarction (MI) and target vessel revascularization (TVR). RESULTS: Overall, The prevalence of true bifurcation lesions, which included Medina classification (1,1,1), (1,0,1), or (0,1,1), was similar between-groups (non-FKB: 37.0% vs. FKB: 39.6%, P = 0.49). At mean 4 years follow-up, rates of major adverse cardiovascular events (non-FKB: 10.0% vs. FKB: 7.8%, P = 0.33), death, MI and TVR were not significantly different between-groups. In multivariate propensity-matched regression analysis, FKB was not an independent predictor of adverse outcomes. CONCLUSIONS: For patients treated with one-stent crossover LM to LAD, clinical outcomes appear similar between FKB and non-FKB strategy.

[Clinical features and outcome of eight patients with mediastinal and neck hematoma after transradial cardiac catheterization approach].

OBJECTIVE: The clinical features of patients with mediastinal and/or neck hematoma after transradial cardiac catheterization were reviewed and analyzed to help the clinicians to recognize this complication, and try their best to avoid the complication and treat the complication properly. METHODS: A total of 8 patients with mediastinal and/or neck hematoma after right transradial cardiac catheterization in Fuwai hospital from January 1, 2005 to the end of 2012 were included in this study. Among these 8 patients, 1 patient underwent coronary angiography, 7 patients underwent percutaneous coronary intervention and drug eluting stents were successfully implanted in 6 patients. The clinical data of these patients were analyzed retrospectively. RESULTS: Super slide hydrophilic guild-wire was used in all patients. These patients felt chest pain, dyspnea and neck pain and neck or throat tightness after the procedure. CT scan was performed in all 8 patients and reviewed mediastinal hematoma, 4 patients complicated with neck hematoma, and suspicious laceration on the right subclavian artery or branch of innominate artery were found in 2 patients. Post procedure hemoglobin decrease was evidenced in all 8 patients. Anti-platelet therapy was discontinued until discharge in 2 patients, dual anti-platelet drugs were transiently discontinued or underwent dosage reduction in 4 patients, protamine was administered in 2 patients to neutralize heparin. Blood transfusion was not required, there was no stent thrombosis, and surgery was not indicated for all 8 patients. No complication was reported during follow up. CONCLUSIONS: Mediastinal and/or neck hematoma is a rare complication post transradial catheterization approach. This complication is caused by super slide guild-wire or catheter's injury of small vessels near the aortic arch or subclavian artery, especially with rough manipulation. Neck and mediastinal CT scan should be performed as early as possible for patients with suspect hematoma and prognosis is usually fine with suitable therapy.

Comparison of procedural and long-term outcomes between transradial and transfemoral approach in one-stage intervention for triple vessel coronary artery disease.

OBJECTIVES: The aim of the present study was to evaluate the safety, feasibility, procedural, and long-term outcomes by the transradial (TR) approach as compared to transfemoral (TF) approach in patients with triple vessel coronary artery disease undergoing one-stage percutaneous coronary intervention. BACKGROUND: The feasibility, safety, and efficacy between the TR and TF approach for coronary interventional treatment have been compared in some complex situations including AMI and unprotected left main disease. However, in terms of triple vessel disease (3VD) intervention, there has been no comparison regarding procedural and long-term outcomes between the TR and TF approach. METHODS: A total of 4,974 consecutive patients (TR n = 3,856, TF n = 1,118), who were diagnosed with 3VD without LM disease and underwent one-stage percutaneous revascularization, were enrolled in the study. Procedural results and clinical outcomes were obtained through database and follow-up. We used the propensity score matching method and obtained 930 pairs of patients with comparable baseline data in order to compare the procedural and long-term outcome between TR and TF groups. In the study cohort, risk reduction of all the clinical outcomes were evaluated with Cox's proportional-hazards models. Cumulative incidences concerning safety and efficacy of the cohort were estimated by the Kaplan-Meier method and a comparison was made utilizing the log-rank test. RESULTS: After propensity score matching, the baseline clinical and angiographic characteristics were similar between the 2 groups. Regarding procedural results, no significant differences were observed between the 2 groups, with the exception of a decreased hospital stay (TR 7.49 ± 4.46 days vs. TF 8.63 ± 6.23 days, P < 0.0001) and fewer bleedings (TR 1.0% vs. TF 2.9, P = 0.003) in the TRI group. After an average 21-month follow-up, the all-cause mortality (TR 1.7% vs. TF 4.2%, P = 0.0014; HR 0.44, 0.25-0.79) was significantly lower with TRI patients. Other clinical outcomes were comparable between the 2 groups. CONCLUSIONS: As compared to TFI, TRI for 3VD intervention is feasible, safe, and associated with similar procedural success, shorter hospitalization, reduced bleeding, lower incidence of death, and comparable long-term efficacy.

Long-term clinical outcomes of patients with unprotected left main bifurcation lesions treated with 2-stent techniques.

BACKGROUND: Currently available evidence suggests that outcomes are less favorable when left main (LM) bifurcation lesions are treated with 2-stent techniques compared with a single-stent technique. We aimed to evaluate the long-term outcomes of the 2-stent techniques for treating unprotected LM bifurcation lesions in Chinese patients. METHODS: We enrolled 301 consecutive patients treated with drug-eluting stents (DES) implantation using 2-stent techniques for unprotected LM bifurcation lesions (MEDINA 1, 1, 1, 70.5%). The 2-stent techniques included crush technique, V stenting, T stenting, and Culottes stenting. After stenting, both vessels were redilated at a high pressure before final kissing balloon (FKB). Clinical and angiographic data were analyzed. The primary endpoints were major adverse cardiac events (MACE), which included death, myocardial infarction, and target lesion revascularization. RESULTS: Immediate procedural success was obtained in all cases with a FKB success rate of 95.3%. Follow-up data were available for all patients. The overall incidence of angiographic in-stent restenosis (ISR) rate was 20.3% and most ISRs were of the focal type. During long-term follow-up (mean duration, (54 ± 22) months), the cumulative incidence of MACE was 11.0%, with 8 (2.7%) deaths, 7 (2.3%) myocardial infarctions, and 18 (6.0%) repeated lesion revascularization. MACEs in high SYNTAX score terciles were significantly higher compared with those in low and intermediate SYNTAX score terciles (P = 0.001). CONCLUSIONS: Although percutaneous coronary intervention (PCI) with 2-stent technique for unprotected LM bifurcation lesions was accompanied with a slightly high incidence of ISR, the long-term clinical follow-up is acceptable. Technical modifications and stent innovations may further improve both the angiographic and clinical outcomes for patients with LM bifurcation disease treated by PCI.

Can "Hybrid stent implantation" improve long-term safety without adversely affecting efficacy when treating multilesion coronary artery disease in the drug-eluting stent era?

BACKGROUND: Though drug-eluting stent (DES) almost solved a problem of restenosis, safety issues related to stent thrombosis are still the major concern of DES. We hypothesized that hybrid stent implantation may decrease the use of DES, probably improving the long-term safety but not affecting efficacy adversely when treating multilesion coronary artery disease in the DES era. METHODS: From April 2004 to October 2006, 848 patients with multilesion disease underwent hybrid stent implantation. During the same period 5647 patients with multilesion coronary heart disease were treated by exclusive DES implantation in Fu Wai Hospital. According to propensity score matching, we chose 823 pairs of patients with multileison coronary artery disease for inclusion into our study. We obtained the 24-month clinical outcome including death, myocardial infarction (MI), thrombosis, target lesion revascularization (TLR), target vessel revascularization (TVR), and major adverse cardiac events (MACE, the composite of death, MI, and TVR). We used Cox's proportional-hazard models to assess relative risks of all the outcome measures after propensity match. RESULTS: At 24 months, patients in the hybrid stent implantation group showed a significantly higher risk of TLR (8.39% vs. 3.28%, HR 2.38, 95%CI: 1.50 - 3.70), TVR (11.07% vs. 6.32%, HR 1.61, 95%CI: 1.15 - 2.27) and MACE (13.75% vs. 8.75%, HR 1.37, 95%CI: 1.02 - 1.85). No significant difference was apparent in terms of mortality (1.22% vs. 1.70%, HR 0.55, 95%CI: 0.24 - 1.25), MI (1.95% vs. 2.31%, HR 0.73, 95%CI: 0.37 - 1.42), or thrombosis (definite + probable) (0.73% vs. 1.58%, HR 0.40, 95%CI: 0.15 - 1.05). CONCLUSIONS: In patients with multilesion coronary artery disease, the exclusive DES implantation was associated with significantly lower risks of TLR, TVR and MACE, and the hybrid stent implantation did not result in any significant improvements regarding safety issues. Prospective studies are needed to confirm our results.

Impact of depressed left ventricular function on outcomes in patients with three-vessel coronary disease undergoing percutaneous coronary intervention.

BACKGROUND: Patients with multivessel coronary artery disease and depressed left ventricular ejection fraction (LVEF) represent a high risk group of patients for coronary revascularization. There are limited data on percutaneous coronary intervention treatment in this population. METHODS: Among a cohort of 4335 patients with three-vessel disease with or without left main disease undergoing percutaneous coronary intervention, 191 patients had LVEF < 40% (low ejection fraction (EF)) and 4144 patients had LVEF ≥ 40%. In-hospital and long-term outcomes were examined according to LVEF. RESULTS: The estimated two-year rates of major adverse cardiac events, cardiac death, and myocardial infarction were significantly higher in the low EF group (19.64% vs. 8.73%, Log-rank test: P < 0.01; 10.30% vs. 1.33%, Log-rank test: P < 0.01, and 10.32% vs. 2.28%, Log-rank test: P < 0.01 respectively), but there was no difference in the rates of target vessel revascularization (6.18% vs. 6.11%, Log-rank test: P = 0.96). Using the Cox proportional hazard models, LVEF < 40% was a significant risk factor for cardiac death, myocardial infarction, and major adverse cardiac events (OR (95%CI): 4.779 (2.369 - 9.637), 2.673 (1.353 - 5.282), and 1.827 (1.187 - 2.813) respectively), but was not a statistically significant risk factor for target vessel revascularization (OR (95%CI): 1.094 (0.558 - 2.147)). CONCLUSION: Among patients undergoing percutaneous coronary intervention for multivessel coronary artery disease, left ventricular dysfunction remains associated with further risk of cardiac death in-hospital and during long-term follow-up.

Clinical and angiographic correlates of left ventricular dysfunction in patients with three vessel coronary disease.

BACKGROUND: Among patients with advanced multivessel coronary disease, left ventricular (LV) function is widely variable, and clinical and angiographic correlates of ventricular dysfunction remain to be defined. METHODS: Among 73 339 patients undergoing diagnostic cardiac catheterization at a single center in China, patients with left ventriculographic assessment were identified with three-vessel coronary disease with or without left main involvement. Clinical and angiographic characteristics were examined among patients with normal or varying extent of LV dysfunction, and predictors of LV impairment (ejection fraction (EF): < 25%, 25% - 40% or > 40%) were determined. RESULTS: Among 11 950 patients identified with three-vessel coronary disease, the sample distribution of LVEF was > 40%, n = 10 776; 25% - 40%, n = 948; < 25%, n = 226. Patients with reduced LV function (< 40%) more commonly were male and had a history of myocardial infarction (MI), diabetes or unstable angina. Hypertension was more frequent in those with LVEF ≥ 40%. In a multivariate Logistic regression analysis, prior MI (odds ratio (OR), 3.37; 95% confidence interval (CI), 2.96 - 3.84) was most predictive of LVEF < 40%, followed by male gender, diabetes, and presentation with unstable angina. For LVEF < 25%, only prior MI was identified as a significant correlate of severe LV dysfunction (OR 4.06, 95%CI 3.06 - 5.39). Following exclusion of patients with previous MI (n = 7416), male gender and diabetes were predictive of LVEF < 40%, yet presentation with unstable angina was the only factor significantly associated with LVEF < 25%. CONCLUSION: Among individuals identified with three-vessel coronary disease with or without left main involvement, previous MI was the most significant risk factor of LV dysfunction.

Sirolimus-eluting stents for treatment of drug-eluting versus bare-metal stents restenosis: 42-month clinical outcomes from a Chinese single center.

BACKGROUND: Restenosis of bare-metal stents (BMS) and drug-eluting stents (DES) has been increasingly treated with sirolimus-eluting stents (SES), but the long-term outcomes are unknown. METHODS: In our study, 388 consecutive patients (144 DES restenosis and 244 BMS restenosis) with 400 lesions (147 DES restenosis and 253 BMS restenosis) treated with SES were included. The rates of target lesion revascularization (TLR) and major adverse cardiac events (MACE) at 42 months were analyzed. RESULTS: At the mean follow-up of 42 months, the rates of death (3.5% vs. 3.3%, P = 1.000) and myocardial infarction (2.8% vs. 1.2%, P = 0.431) in the DES group and BMS group were comparable. Compared with the BMS group, ischemia-driven TLR occurred with a higher frequency in the DES group (18.8% vs. 10.7%, P = 0.024). This translated into an increased rate of MACE in the DES group (22.2% vs. 14.0%, P = 0.034). Stent thrombosis occurred with a similar frequency in both groups (2.8% vs. 1.6%, P = 0.475). Multivariate analysis showed that DES restenosis (OR = 1.907, 95%CI 1.108 - 3.285, P = 0.020) and smoking (OR = 2.069; 95%CI 1.188 - 3.605; P = 0.010) were independent predictors of MACE. CONCLUSIONS: Although SES implantation appears to be safe and effective, it was associated with higher TLR recurrence for DES than BMS restenosis.

Current treatment status in patients with severe aortic valve stenosis and outcome of long term follow-up at advanced age: a Chinese single center study.

BACKGROUND: Surgical aortic valve replacement is the standard treatment for patients with severe aortic stenosis, but some registries have indicated that 30% to 60% of these patients are not treated surgically, usually due to advanced age and/or comorbidities. This single center study in China investigated the current treatment status in the patients with severe aortic stenosis and evaluated the long term clinical outcome in advanced age patients whether or not undergoing aortic valve replacement. METHODS: Clinical data of 867 consecutive patients with severe aortic stenosis between January 2000 and December 2006 were retrospectively analyzed. The patients ≥ 65 years old were followed up by telephone or information from medical records. The primary end-point was all-cause mortality. RESULTS: The patients' average age was (52 ± 19) years (range, 1 - 91 years), and 34% were women. The percentages of the patients aged < 15 years, between 15 and 34 years, between 35 and 54 years, between 55 and 64 years, between 65 and 74 years, and ≥ 75 years who underwent surgical aortic valve replacement were 82.3%, 87.2%, 88.8%, 78.2%, 65.3% and 22.2% respectively. In the patients (n = 256) ≥ 65 years old, 43.4% had New York Heart Association class III and IV symptoms, 39.1% had hypertension, 33.2% had coronary heart disease, and 3.1% had stroke. In the patients not undergoing aortic valve replacement, 1.6% had renal insufficiency, 4.7% had chronic obstructive pulmonary disease, 2.0% had critical hematopathy, and 0.4% had mammary cancer. A total of 186 (72.7%) patients finished the follow-up, and the average duration of the follow-up was (60 ± 26) months. In the patients between 65 and 74 years old, the total deaths and cardiac deaths in the patients undergoing aortic valve replacement decreased significantly compared with those with conservative treatment (10.3% vs. 53.7%, P < 0.001 and 6.3% vs. 50.7%, P < 0.001). Similarly, in the patients ≥ 75 years old, there was a significant difference between patients who had surgery and those who had conservative treatment in the total deaths and cardiac deaths (21.4% vs. 63.3%, P = 0.007 and 14.3% vs. 46.9%, P = 0.033). The total deaths in the patients aged between 65 and 74 years were significantly fewer compared with = 75 years old patients (25.4% vs. 54.0%, P < 0.001). Cox regression revealed that aortic valve replacement was the only independent predictor of mortality (HR 0.183; 95% CI, 0.101 - 0.332, P < 0.001). CONCLUSIONS: This single centre study showed that surgical aortic valve replacement was still the standard treatment for the patients with severe aortic stenosis and had a satisfying prognosis. However, the high risk patients with advanced age and comorbidities usually selected conservative treatment and had an unfavorable prognosis.