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Purpose To compare risks of interstitial lung disease (ILD) between patients treated with dronedarone versus other antiarrhythmics. Methods Parallel retrospective cohort studies were conducted in the United States Department of Defense Military Health System database (DoD) and the HealthCore Integrated Research Database (HIRD). Study patients were treated for atrial fibrillation (AF) with dronedarone, amiodarone, sotalol, or flecainide. Propensity score matching was employed to create analysis cohorts balanced on baseline variables considered potential confounders of treatment decisions. The study period of July 20, 2008 through September 30, 2014 included a 1‐year baseline and minimum 6 months of follow‐up, for patients with drugs dispensed between July 20, 2009 and March 31, 2014. Suspect ILD outcomes were reviewed by independent adjudicators. Cox proportional hazards regression compared risk of confirmed ILD between dronedarone and each comparator cohort. A sensitivity analysis examined the effect of broadening the outcome definition. Results A total 72 ILD cases (52 DoD; 20 HIRD) were confirmed among 27 892 patients. ILD risk was significantly higher among amiodarone than dronedarone initiators in DoD (HR = 2.5; 95% CI = 1.1–5.3, p = 0.02). No difference was detected in HIRD (HR = 1.0; 95% CI = 0.4–2.4). Corresponding risks in sotalol and flecainide exposure groups did not differ significantly from dronedarone in either database. Conclusions ILD risk among AF patients initiated on dronedarone therapy was comparable to or lower than that of amiodarone initiators, and similar to that of new sotalol or flecainide users. This finding suggests that elevated ILD risk associated with amiodarone does not necessarily extend to dronedarone or other antiarrhythmic drugs.

Pancreatic neuroendocrine tumors (PanNETs) are indolent pancreatic tumors derived from neuroendocrine cells in pancreatic islets. To date, reliable predictors for identifying patients at high risk for recurrence after curative cancer resection are lacking. We aimed to determine independent predictors for high-risk PanNETs and patient outcomes after surgery. We analyzed relevant clinicopathological parameters in 319 consecutive patients of derivation cohort 1 and 106 patients of validation cohort 2 who underwent pancreatectomy and were diagnosed with PanNETs. Association of tumor characteristics with recurrence-free survival (RFS) and overall survival (OS) was evaluated using Cox regression. PanNET grade 3 (G3), pancreatic duct dilatation, and perineural invasion were independent prognostic factors for RFS and were significantly associated with early recurrence (within 1.5 years) of PanNETs after curative resection (P = 0.019, P

ObjectiveThis study retrospectively characterized the immune infiltrating profile in nonfunctional pancreatic neuroendocrine tumors (NF-PanNETs).MethodsTumor tissues from the 109-patient Fudan cohort and a 73-patient external validation set were evaluated by immunohistochemistry for 9 immune cell types: tumor-infiltrating neutrophils (TINs), tumor-associated macrophages (TAMs), CD11c+ dendritic cells, anti-NCR1+ natural killer (NK) cells, CD4+ and CD8+ T cells, CD45RO+ memory T cells, FOXP3+ regulatory T cells (Tregs), and CD20+ B cells.ResultsTINs were primarily distributed in the intratumoral area, dendritic cells and NK cells were scattered evenly in intratumoral and stromal areas, and Tregs were rarely detected. The remaining 5 cell types were primarily present in peritumoral stroma. Total TINs (P < .001) and TAMs (P = .002) increased as NF-PanNET grade rose. Kaplan-Meier analyses showed that high intratumoral TINs, total TAMs, and stromal CD4+ T-cell infiltration correlated with shorter recurrence-free survival (RFS, P = .010, P = .027, and P = .035, respectively) and overall survival (OS, P = .017, P = .029, and P = .045, respectively). Additionally, high intratumoral CD8+ T cell infiltration correlated with prolonged RFS (P = .039). Multivariate Cox regression demonstrated that intratumoral TINs, World Health Organization (WHO) classification, and eighth edition of the American Joint Committee on Cancer tumor-node-metastasis staging system (AJCC8th TNM) were independent factors for RFS (P = .043, P = .023, and P = .029, respectively), whereas intratumoral TINs and WHO classification were independent factors for OS (P = .010 and P = .007, respectively). Furthermore, the combination of TINs, WHO classification, and AJCC8th TNM remarkably improved prognostic accuracy for RFS. These results have been verified in the external validation set.ConclusionIntratumoral TINs are an independent and unfavorable predictor of postoperative NF-PanNETs. A combination of TINs, WHO classification, and AJCC8th TNM could improve prognostic accuracy for RFS.

Purpose: The systemic inflammation response index (SIRI), based on peripheral neutrophil, monocyte, and lymphocyte counts, was recently emerged and used as a novel tool in predicting prognosis in different types of cancer. Our aim was to investigate the clinical significance of preoperative SIRI in patients with resectable pancreatic ductal adenocarcinoma (PDAC). Materials and methods: The SIRI was developed in a training cohort of 371 PDAC patients undergoing radical surgery between 2010 and 2013 and validated in a validation cohort of 310 patients from 2014 to 2015. Baseline clinicopathologic characteristics, preoperative laboratory parameters and follow-up information were collected. The optimal cutoff value of SIRI was determined by receiver operating characteristic curve. Univariate and multivariate analysis were performed to analyze the prognostic value of SIRI. Results: The optimal cutoff value of SIRI stratified patients into low SIRI group (≤0.69) and high SIRI group (>0.69). Survival analysis showed that the median overall survival (OS) and recurrence-free survival (RFS) were significantly better in patients with low SIRI. The SIRI was an independent predictor of OS and RFS in multivariate analysis. In addition, SIRI remained its prognostic significance both in patients with early-stage diseases and in patients with normal carbohydrate antigen 19-9 levels. High SIRI indicated poor treatment response for patients who received postoperative adjuvant chemotherapy. Conclusion: Preoperative SIRI was an independent prognostic indicator of poor outcomes in PDAC patients after radical resection. It might assist clinicians to identify high-risk patients and choose the optimal individualized treatment strategy.

BackgroundTertiary lymphoid structures (TLS) are associated with favorable survival and play a critical role in most solid tumors. However, investigations of TLS are lacking in patients with grade 1 or grade 2 (G1/G2) non-functional pancreatic neuroendocrine tumors (NF-PanNETs). This study aimed to investigate the presence, cellular composition, association with tumor-infiltrating immune cells, and prognostic value of TLS in G1/G2 NF-PanNETs.MethodsTumor tissues from a 182-patient Fudan cohort and a 125-patient external validation set were assessed by H&E staining, immunohistochemistry, and/or multispectral fluorescent immunohistochemistry.ResultsTLS were identified in more than one-third of patients with G1/G2 NF-PanNETs and were located peritumorally, either just outside the tumor tissue or in the stromal area. TLS were mainly composed of B-cell follicles with germinal centers and T-cell zones with dendritic cells. Kaplan-Meier analyses showed that the presence of TLS correlated with both longer recurrence-free survival (RFS, p8th) tumor-node-metastasis (TNM) stage were independent prognostic factors for RFS (p=0.004, p=0.001, and p8th TNM stage.ConclusionsThe presence of TLS is an independent and favorable predictor of resected G1/G2 NF-PanNETs, which may play a role in cancer immunobiology.

Pancreatic ductal adenocarcinoma (PDAC) is a devastating malignancy with poor prognosis. Many preoperative biomarkers can predict postoperative survival of PDAC patients. In this study, we created a novel ratio index based on preoperative liver function test, γ‐glutamyltransferase‐to‐albumin ratio (GAR), and evaluated its prognostic value in predicting clinical outcomes of PDAC patients following radical surgery. We retrospectively enrolled 833 PDAC patients who had underwent radical surgery at our institution between January 2010 and January 2017. Patients were divided into two groups according to the cut‐off value of GAR. Univariate and multivariate survival analysis between the groups were evaluated. TNM stage, GAR, preoperative serum carbohydrate antigen 19‐9 (CA19‐9) and tumor differentiation were combined to generate a more accurate prognostic model. The optimal cut‐off value of GAR was 0.65. Significant correlations were found between GAR and tumor location, tumor size, vascular invasion, obstructive jaundice, biliary drainage and parameters of liver function test. Univariate and multivariate analysis showed that high level of GAR independently predicted poorer postoperative overall survival (OS, P < 0.001) and recurrence‐free survival (RFS, P < 0.001). Subgroup analysis demonstrated that GAR was predictive of survival in patients without biliary obstruction or severely impaired liver function. In addition, integration of GAR, preoperative serum CA19‐9, and tumor differentiation into TNM staging system could better stratify the prognosis for PDAC patients compared with TNM stage alone. Our study demonstrates that preoperative GAR is an independent prognostic factor for prediction of surgical outcomes in PDAC patients. Combination of TNM stage, GAR, preoperative serum CA19‐9, and tumor differentiation can enhance the prognostic accuracy.

Radical surgical resection represents the only hope of cure for pancreatic neuroendocrine tumor (PanNET). Adjuvant therapy is rarely used because there is no evidence to distinguish patients with high recurrence risk. Here we investigated the recurrence feature of resected PanNET and established a novel risk stratification to predict its recurrence. We analyzed 505 PanNET patients who underwent R0 resection at our institute from January 2004 through May 2015. The median follow-up was 71months (range: 12months-143months), 129 patients (25.5%) experienced recurrence with median disease-free survival (mDFS) of 19months. Restricted cubic spline (RCS) functions revealed a positive, linear relationship between Ki-67 index and recurrence. Multivariate analysis showed T stage, N stage, insulinoma and Ki-67 index were independent predictors of recurrence (P

Effect of atorvastatin inhibition of endoplasmic reticulum stress and amelioration of atherosclerosis through AMPK pathway were studied. Eight-week-old male apolipoprotein E-deficient (ApoE−/−) mice were fed with high-fat diet for 2 weeks and randomly divided into two groups: Atorvastatin treatment group was given atorvastatin (5 mg/kg/day) injection for a total of 6 weeks; control group was given the same dose of PBS through intraperitoneal injection for a total of 6 weeks. H&E staining was used to detect plaque size; immunohistochemical staining was used to detect T cells, macrophages and phospho-protein kinase-like ER kinase (phospho-PERK) in localized plaques. Proteins were extracted from mouse thoracic and abdominal aortic tissues. Western blot analysis was used to detect the protein expression levels of endoplasmic reticulum stress-related molecules phospho-eukaryotic initiation factor-2α (p-eIF2α), eukaryotic initiation factor (eIF2a), and sliced x-box binding protein 1 (sXBP-1). Cultured human umbilical vein endothelial cells (HUVECs), induced endoplasmic reticulum stress with human oxidized low density lipoprotein (ox-LDL), were treated with atorvastatin, AMPK agonist 5-amino-4-imidazolecarboxamide riboside-I-β-D-ribofuranoside (AICAR) and AMPK-DN that expressed a dominant-negative mutant of AMPK. Western blot analysis was used to test the expression levels of endoplasmic reticulum stress-related molecules p-elF2a and sXBP-1. The area of aortic plaques in atorvastatin group was obviously decreased, and the infiltrations of CD3+ T cells and macrophages in the localized plaques were reduced. The endoplasmic reticulum stress-related proteins sXBP-1 and p-eIF2a were significantly reduced. The results of immunohistochemistry also showed a significant decrease in the level of phospho-PERK (p-PERK) in atorvastatin group. The results in ox-LDL-induced HUVECs showed that atorvastatin inhibited ox-LDL-induced endoplasmic reticulum stress, and the AMPK agonist AICAR also had the same effect, which was offset by DN-AMPK treatment. Atorvastatin inhibits ER stress both in vitro and in vivo and this protective effect is mediated by AMPK activation.

Diabetic ketoacidosis (DKA) is a common complication of type 1 diabetes mellitus (T1DM). We found that the incidence of DKA was 55.5 per 1000 person-years in US commercially insured patients with T1DM; age-sex-standardized incidence decreased at an average annual rate of 6.1% in 2018–2019 after a steady increase since 2011.

Purpose Dronedarone may increase digoxin plasma levels through inhibition of P-glycoprotein. Using real-world data, we evaluated the risk of digitalis intoxication in concomitant users of dronedarone and digoxin compared digoxin-alone users. Methods We used the Clinformatics DataMart, a US claims database, to identify adult patients with atrial fibrillation (AF) or atrial flutter (AFL) who concomitantly used dronedarone and digoxin and those who used digoxin alone between July 2009 and March 2016. Digitalis intoxication during follow-up until March 2016 was ascertained using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) and International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM). Adjusted hazard ratios (HR) for digitalis intoxication in concomitant users versus users of digoxin alone were estimated, controlling for age, sex, cohort entry year, number of medical encounters for AF or AFL, history of congestive heart failure, diabetes, hypertension, stroke, myocardial infarction, renal failure, use of drugs interacting with digoxin, and digoxin dose. Findings Overall, 524 concomitant users and 32,459 users of digoxin alone were identified, among which 3 and 301 events of digitalis intoxication occurred during follow-up, respectively. Incidence rates were 17.25 and 9.17 cases per 1000 person-years, respectively. The adjusted HR for digitalis intoxication in concomitant users versus users of digoxin alone was 1.56 (95% CI, 0.50-4.88; P = 0.45). When digitalis intoxication was defined by ICD-9-CM and ICD-10-CM codes accompanied by laboratory testing for digoxin/digitoxin or hospitalization within 30 days, no events occurred in the concomitant users and 40 events occurred in the users of digoxin alone (incidence rate of 1.22 cases per 1000 person-years). Implications Concomitant use of dronedarone and digoxin was uncommon in this study, and no significant increase in the risk of digitalis intoxication with concomitant use was found.

Background The aim of this study was to assess the immune profile within the microenvironment of pancreatic ductal adenocarcinoma (PDAC), and to investigate the prognostic value of intratumoral infiltrating immune/inflammatory cells (IICs) in patients after surgery. Methods Eighteen phenotypic markers representing 11 types of IIC and the protein products of genes TP53, CDKN2A/p16 and SMAD4/DPC4 were assessed by immunohistochemistry of specimens from patients with pancreatic cancer. The expression of IICs and the mutational status of the genes were correlated with tumour recurrence and survival, and results were validated in an independent cohort. Results CD15+ neutrophils, CD20+ B cells and CD206+ tumour-associated macrophages were seen frequently in tumours, and their presence was associated with reduced survival in a cohort of 79 patients. Expression of CD4+ T helper cells, CD8+ cytotoxic T lymphocytes and CD117+ mast cells was associated with a favourable prognosis. A weighted Cox regression recurrence-predictive model was constructed that showed good correlation of IICs and gene mutations. A combination of CD15, CD206, CD117 and Smad4 expression was independently associated with overall (hazard ratio (HR) 3·63, 95 per cent c.i. 2·18 to 6·04; P < 0·001) and recurrence-free (HR 2·93, 1·81 to 4·75; P < 0·001) survival. These findings were validated in an independent cohort (151 patients) and in 54 tissue samples obtained by preoperative endoscopic ultrasound-guided fine-needle aspiration. Conclusion PDAC has a unique immunosuppressive phenotype that is associated with characteristic gene mutations, disease recurrence and survival after pancreatectomy. Surgical relevanceThe immune microenvironment plays a critical role in the development of pancreatic ductal adenocarcinoma (PDAC). PDAC is associated with mutations in major driver genes, including KRAS, TP53, CDKN2A/p16 and SMAD4/DPC4.This study shows that the microenvironment of PDAC has a unique immunosuppressive phenotype, which may be driven by oncogene mutations. Patients with PDAC with a highly immunosuppressive profile tended to have poor postoperative survival. A model including three intratumoral infiltrating immune markers (CD15+, CD206+ and CD117+) and a SMAD4 mutation can be used to predict recurrence and survival in patients after surgery for PDAC.

The clinicopathological and prognostic features of insulinoma with synchronous metastases are unclear. This study aimed to verify the distinct clinicopathological and prognostic features of insulinoma with synchronous distant metastasis.Patients with pancreatic neuroendocrine tumor (PanNET) were retrospectively enrolled and divided into cohort 1 (Fudan University Shanghai Cancer Center) and cohort 2 (Surveillance, Epidemiology, and End Results Program database). Both cohorts were further divided into three subgroups: insulinoma, nonfunctioning pancreatic neuroendocrine tumor (NF-PanNET), and non-insulinoma functioning pancreatic neuroendocrine tumor (NiF-PanNET).Cohorts 1 and 2 comprised 505 and 2761 patients (1566 M0 patients and 1195 M1 patients), respectively. In cohort 1 and cohort 2 M0 subgroup, insulinoma showed longer disease-free survival, overall survival (OS), and disease-specific survival (DSS) than NiF-PanNET and NF-PanNET (not reached vs. 48 and 60months, p 0.001; 183months vs. 87 and 109months, p 0.001; 247months vs. 121 and 140months, p = 0.002). However, in cohort 2 M1, the mDSS for metastatic insulinoma was shorter than that for NiF-PanNET (31months vs. 61months, p = 0.045), while the mDSS and mOS were similar to those for NF-PanNET. The percentage of T1 and N0 patients was similar between the metastatic insulinoma subgroup and NiF-PanNET and NF-PanNET subgroups. The Ki-67 index and recurrence had a positive linear relationship only for NiF-PanNET and NF-PanNET (p = 0.009).Insulinoma with synchronous metastasis showed clinicopathological and prognostic characteristics similar to those of NF-PanNET. Metastatic insulinoma had worse prognosis than non-insulinoma F-PanNET. These findings may help in the clinical management of metastatic insulinoma.

The objective of this study was to compare the risks of breast cancer in women treated with insulin glargine and NPH using claims data. The MarketScan and Clinformatics databases were used to identify patients prescribed glargine or NPH in the study periods of January 2007 to March 2016 and July 20to June 2016, respectively. The risks of breast cancer in patients prescribed glargine relative to NPH were compared using three approaches: (1) on-treatment, (2) intent-to-treat and (3) time-dependent analysis. The overall and follow-up period stratified adjusted hazard ratios (aHRs) for breast cancer for glargine compared to NPH were obtained using Cox proportional hazards modelling controlling for potential confounders.In the MarketScan database, 75,422 glargine and 21,491 NPH patients were identified, of which 42,491 glargine and 7,826 NPH patients were new users. Using the Clinformatics database, 65,648 glargine and 16,194 NPH patients were identified, including 47,118 and 10,560 new users, respectively. The overall aHRs for breast cancer for glargine compared to NPH ranged from 0.90 (95% CI: 0.76-1.07) in the time-dependent analysis for all users in the Clinformatics database to 1.30 (95% CI: 0.76-2.25) in the on-treatment analysis for new users in the MarketScan database. In the MarketScan database, the aHRs stratified by the follow-up period (< 1, 1 - < 3, 3 - < 5 and ≥ 5 Years) ranged from 0.67 to 1.63. In the Clinformatics database the corresponding aHRs ranged from 0.85 to 1.40. All 95% confidence intervals (CIs) included the null value of 1. These findings suggest that the risk of breast cancer in patients prescribed glargine was not different from that in NPH patients. In conclusion, the risks of breast cancer were not different between patients prescribed glargine and NPH. Additionally, no association between glargine and breast cancer was observed with follow-up longer than 5 years. Disclosure P. Boyle: Other Relationship; Self; Sanofi. C. Wu: Employee; Self; Sanofi. K. Sharma: Employee; Spouse/Partner; Sanofi US. S.L. Lin: Employee; Self; Sanofi. Employee; Spouse/Partner; Bristol-Myers Squibb Company. J. Juhaeri: Employee; Self; Sanofi. Other Relationship; Spouse/Partner; Sanofi.

Pancreatic cancer is currently one of the deadliest solid malignancies and pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer. In the past decade, diagnostics and surgical techniques for PDAC have been evolving steadily; however, clinical outcomes of patients with PDAC have shown little, if any, improvement. Subgroup classification based on accurate prediction of prognosis in patients with pancreatic cancer is important for treatment selection and clinical decision-making. The traditional method to evaluate prognosis relies on the TNM staging system, but it may not reflect the true status of every patient due to individual biological differences. Metabolomics is a field of study that involves the identification and quantification of metabolites present in a biological system. Analysis of metabolic differences between cancerous and noncancerous tissues can provide novel insights into tumor biology that are closely associated with disease prognosis and diagnosis. Therefore, evaluation of metabolic tumor burden may improve the accuracy of the clinical decision-making process, thereby facilitating optimization of the treatment strategies for pancreatic cancer.

Pancreatectomy is associated with significant morbidity and unpredictable outcome, with few diagnostic tools to determine, which patients gain the most benefit from this treatment, especially before the operation. This study aimed to define a preoperative signature panel of serum markers to indicate response to pancreatectomy for pancreatic cancer. Over 1000 patients with pancreatic cancer treated at two independent high-volume institutions were included in this study and were divided into three groups, including resected, locally advanced and metastatic. Eight serum tumor markers most commonly used in gastrointestinal cancers were analyzed for patient outcome. Preoperative CA19-9 independently indicated surgical response in pancreatic cancer. Patients with CA19-9 ≥1000 U/mL generally had a poor surgical benefit. However, a subset of these patients still achieved a survival advantage when CA19-9 levels decreased postoperatively. CEA and CA125 in the presence of CA19-9 ≥1000 U/mL could independently predict the non-decrease of CA19-9 postoperatively. The combination of the three markers was useful for predicting a worse surgical outcome with a median survival of 5.1 months vs. 23.0 months (p

Background— A simple risk score to predict long-term mortality after percutaneous coronary intervention (PCI) using preprocedural risk factors is currently not available. In this study, we created one by simplifying the results of a Cox proportional hazards model. Methods and Results— A total of 11 897 patients who underwent PCI from October through December 2003 in New York State were randomly divided into derivation and validation samples. Patients’ vital statuses were tracked using the National Death Index through the end of 2008. A Cox proportional hazards model was fit to predict death after PCI using the derivation sample, and a simplified risk score was created. The Cox model identified 12 separate risk factors for mortality including older age, extreme body mass indexes, multivessel disease, a lower ejection fraction, unstable hemodynamic state or shock, several comorbidities (cerebrovascular disease, peripheral vascular disease, congestive heart failure, chronic obstructive pulmonary disease, diabetes mellitus, and renal failure), and a history of coronary artery bypass graft surgery. The C statistics of this model when applied to the validation sample were 0.787, 0.785, and 0.773 for risks of death within 1, 3, and 5 years after PCI, respectively. In addition, the point-based risk score demonstrated good agreement between patients’ observed and predicted risks of death. Conclusions— A simple risk score created from a more complicated Cox proportional hazards model can be used to accurately predict a patient’s risk of long-term mortality after PCI.

Caveolin-1 exhibits a stage-dependent, functional fluctuation during pancreatic cancer development, but the underlying mechanisms remain unclear. Here, we report that cavin-1, a structural protein of caveolae, modulates the oncogenic function of caveolin-1 and cooperates with caveolin-1 to enhance pancreatic cancer aggressiveness. Cavin-1 expression is associated with caveolin-1 in pancreatic cancer tissue samples and cell lines, and predicts the metastatic potential of pancreatic cancer. Interactome analyses further revealed the physical interaction of cavin-1 and caveolin-1 and their colocalization in pancreatic cancer cells. Cavin-1 stabilizes caveolin-1 expression or activity by inhibiting its internalization and subsequent lysosomal degradation. More in-depth functional experiments showed that caveolin-1-enhanced aggressiveness of pancreatic cancer cells is dependent on the presence of cavin-1. In contrast, cavin-1 depletion inhibited the invasion and metastasis of pancreatic cancer cells, which could not be restored by caveolin-1-rescue construct. Tissue microarray analyses in two independent clinic cohorts also supported the augment of cavin-1 on the prognostic potency of caveolin-1, and showed that combination of cavin-1 with caveolin-1 predicted worse survival in pancreatic cancer patients. Of note, the phenotypes because of cavin-1 could not be achieved by other cavins such as cavin-2, and the tumor-promoting role of cavin-1 in pancreatic cancer was found to be largely dependent on caveolin-1 expression, which highlights the critical role of cavin-1/caveoin-1 in pancreatic cancer progression, and suggests that the interruption of cavin-1/caveolin-1 interaction is a promising therapeutic strategy for pancreatic cancer.

Few studies have examined differences in long-term mortality between coronary artery bypass graft surgery and stenting with drug-eluting stents (DES) for multivessel disease without left main coronary artery stenosis. This study compares the risks of long-term mortality between these 2 procedures during a follow-up of up to 5 years.Patients who underwent isolated bypass surgery (n=13,212) and stenting with DES (n=20,161) between October 2003 and December 2005 in New York State were followed for their vital status through 2008. To control for treatment selection bias, bypass and stenting patients were matched on age, number of diseased coronary vessels, presence of proximal or nonproximal left anterior descending (LAD) artery disease, and propensity of undergoing bypass surgery. Five-year survival rates for the 2 procedures were compared and hazard ratios for death of bypass surgery compared with stenting were obtained.The respective 5-year survival rates in the 8,121 pairs of matched bypass and stenting patients were 80.4% and 73.6% (p0.001), and the risk of death after bypass surgery was 29% lower than for stenting (hazard ratio = 0.71, 95% confidence interval: 0.67 to 0.77, p0.001). Significantly lower risks of death for bypass surgery were observed in patients with LAD artery disease but not in patients without LAD artery disease. Significantly lower risks of death for bypass surgery were also found in all patient subgroups defined by the presence of selected baseline risk factors.Bypass surgery is associated with lower risk of death than stenting with DES for multivessel disease without left main stenosis.

Background— The impact of incomplete revascularization (IR) on adverse outcomes after percutaneous coronary intervention remains inconclusive, and few studies have examined mortality during follow-ups longer than 5 years. The objective of this study is to test the hypothesis that IR is associated with higher risk of long-term (8-year) mortality after stenting for multivessel coronary disease. Methods and Results— A total of 13 016 patients with multivessel disease who had undergone stenting procedures with bare metal stents in 1999 to 2000 were identified in the New York State's Percutaneous Coronary Intervention Reporting System. A logistic regression model was fit to predict the probability of achieving complete revascularization (CR) in these patients using baseline risk factors; then, the CR patients were matched to the IR patients with similar likelihoods of achieving CR. Each patient's vital status was followed through 2007 using the National Death Index, and the difference in long-term mortality between IR and CR was compared. It was found that CR was achieved in 29.2% (3803) of the patients. For the 3803 pair-matched patients, the respective 8-year survival rates were 80.8% and 78.5% for CR and IR ( P =0.04), respectively. The risk of death was marginally significantly higher for IR (hazard ratio=1.12; 95% confidence interval, 1.01–1.26, P =0.04). The 95% bootstrap confidence interval for the hazard ratio was 0.98 to 1.32. Conclusions— IR may be associated with higher risk of long-term mortality after stenting with BMS in patients with multivessel disease. More prospective studies are needed to further test this association.

Objectives To examine the circadian pattern of cardiac autonomic modulation (CAM) and its attributes in general population. Methods We obtained 24-h beat-to-beat RR data using a high resolution 12-lead Holter ECG in a community-dwelling sample of 115 non-smokers. We performed heart rate variability (HRV) analysis on the normal RRs from each 5-min segment to obtain time-specific HRV indices: high (HF; 0.15–0.40 Hz) and low (LF; 0.04–0.15 Hz) frequency powers, standard deviation of RR intervals (SDNN), and the square root of the mean of the sum of the squared differences of the adjacent RR intervals (RMSSD). For each individual, we fit the segment-specific HRV data to a cosine periodic function, and estimated 3 individual-level cosine function parameters to quantify the circadian variation: the mean (M), amplitude (A), and acrophase (θ). We then used a random-effects meta-analysis to summarize the M, A, and θ, and their 95% confidence intervals (CI). Results The mean age was 56 (SD 8) years, with 63% female and 76% white. The averages of M, A and θ (95%CI) of log HF were 3.59 (3.43–3.76) ms2, 0.61 (0.54–0.68) ms2, and 3:10 (2:25–3:55) AM, respectively, and that of RMSSD were 22.3 (20.5–24.1) ms, 6.5 (5.4–7.5) ms, 3:45 (2:55–4:35) AM, respectively. Older age is associated with lower mean of HRV. Males have higher oscillation amplitude than females. The acrophase of LF/HF was earlier in females than in males, and in younger individuals than in older individuals. Conclusions The circadian pattern of CAM can be quantified by 3 cosine parameters of HRV, which are correlated with age and gender.

e13592Background: Diabetes and breast cancer are common diseases in women. Studies of the association have been heterogeneous. The objective of this study was to compare the risks of breast cancer ...

Purpose There are few data on the risk for peripheral neuropathy associated with dronedarone, a newer antiarrhythmic medicine. The objective of this study was to assess whether dronedarone is potentially associated with an increased risk for peripheral neuropathy compared with other antiarrhythmics, including amiodarone, sotalol, flecainide, and propafenone. Methods The MarketScan database was used for identifying patients who were at least 18 years of age, had atrial fibrillation or flutter, and had not been diagnosed with peripheral neuropathy in the 180-day period prior to or on the date of the first prescription of an antiarrhythmic between July 20, 2009, and December 31, 2011. Peripheral neuropathy that occurred during the treatment period for a study drug was ascertained using ICD-9-CM diagnostic codes. For each antiarrhythmic, the incidence rate of peripheral neuropathy was calculated. The adjusted hazard ratio (aHR) for peripheral neuropathy for dronedarone compared with another antiarrhythmic was obtained, with control for age, sex, diabetes mellitus status, and the presence of other comorbidities. Findings The study population included 106,933 patients treated with dronedarone (n = 12,989), amiodarone (n = 45,173), sotalol (n = 22,036), flecainide (n = 14,244), or propafenone (n = 12,491). The incidence rates (per 1000 person–years) of peripheral neuropathy were 1.33 for dronedarone, 2.38 for amiodarone, 1.20 for sotalol, 1.08 for flecainide, and 1.97 for propafenone. The aHRs for peripheral neuropathy for dronedarone relative to other drugs ranged from 0.53 (95% CI, 0.21–1.34) compared with propafenone, to 0.94 (95% CI, 0.38–2.30) compared with sotalol. A new-user analysis showed similar results. Implications The risks for peripheral neuropathy were not significantly different between dronedarone and other antiarrhythmics.

Objectives We sought to compare outcomes for percutaneous coronary intervention patients undergoing complete revascularization (CR) and incomplete revascularization (IR) in the drug-eluting stent era. Background There have been relatively few studies that have examined the impact of IR in patients undergoing coronary stenting, particularly in the era of drug-eluting stents. Methods New York State9s Percutaneous Coronary Intervention Reporting System was used to identify 11,294 stent patients with multivessel disease undergoing either IR or CR in 39 hospitals between October 1, 2003, and December 31, 2004. These patients were followed through December 31, 2005, and IR patients were subdivided based on the number of IR vessels and presence of a chronic total occlusion. Risk-adjusted mortality and mortality/myocardial infarction (MI) for CR and IR patients were compared at 18 months. Results Incomplete revascularization was performed in a total of 7,795 patients (69.0%). Incomplete revascularization was associated with higher 18-month mortality (adjusted hazard ratio [HR]: 1.23, 95% confidence interval [CI]: 1.04 to 1.45) and higher 18-month MI/mortality (adjusted HR: 1.27, 95% CI: 1.09 to 1.47). The risk-adjusted survival rates for CR and IR were 94.9% and 93.8% (p = 0.01). The risk-adjusted survival/freedom from MI rates were 93.3% and 91.7% (p = 0.002). Patients with 2 diseased vessels unattempted with a total occlusion were at highest risk (adjusted survival HR: 1.44, 95% CI: 1.14 to 1.82, risk-adjusted survival 94.9% vs. 92.9%, p = 0.002; and adjusted survival/freedom from MI: 1.50, 95% CI: 1.21 to 1.86, rates 93.3% vs. 90.3%, p Conclusions Patients undergoing coronary stenting who receive IR experience more adverse outcomes even in the era of drug-eluting stents. This has implications for choice of procedure and post-procedural monitoring.

Numerous studies have compared the outcomes of two competing interventions for multivessel coronary artery disease: coronary-artery bypass grafting (CABG) and coronary stenting. However, little information has become available since the introduction of drug-eluting stents.We identified patients with multivessel disease who received drug-eluting stents or underwent CABG in New York State between October 1, 2003, and December 31, 2004, and we compared adverse outcomes (death, death or myocardial infarction, or repeat revascularization) through December 31, 2005, after adjustment for differences in baseline risk factors among the patients.In comparison with treatment with a drug-eluting stent, CABG was associated with lower 18-month rates of death and of death or myocardial infarction both for patients with three-vessel disease and for patients with two-vessel disease. Among patients with three-vessel disease who underwent CABG, as compared with those who received a stent, the adjusted hazard ratio for death was 0.80 (95% confidence interval [CI], 0.65 to 0.97) and the adjusted survival rate was 94.0% versus 92.7% (P=0.03); the adjusted hazard ratio for death or myocardial infarction was 0.75 (95% CI, 0.63 to 0.89) and the adjusted rate of survival free from myocardial infarction was 92.1% versus 89.7% (P0.001). Among patients with two-vessel disease who underwent CABG, as compared with those who received a stent, the adjusted hazard ratio for death was 0.71 (95% CI, 0.57 to 0.89) and the adjusted survival rate was 96.0% versus 94.6% (P=0.003); the adjusted hazard ratio for death or myocardial infarction was 0.71 (95% CI, 0.59 to 0.87) and the adjusted rate of survival free from myocardial infarction was 94.5% versus 92.5% (P0.001). Patients undergoing CABG also had lower rates of repeat revascularization.For patients with multivessel disease, CABG continues to be associated with lower mortality rates than does treatment with drug-eluting stents and is also associated with lower rates of death or myocardial infarction and repeat revascularization.

Background— Off-pump coronary artery bypass graft surgery (OPCAB) has been performed for many years, but its use is increasing in frequency, and it remains an open question whether OPCAB is associated with better outcomes than on-pump coronary artery bypass graft (CABG) surgery. Methods and Results— New York State patients who underwent either OPCAB with median sternotomy (13 889 patients) or on-pump CABG surgery (35 941 patients) between 2001 and 2004 were followed up via New York databases. Short- and long-term outcomes were compared after adjustment for patient risk factors and after patients were matched on the basis of significant predictors of type of CABG surgery. OPCAB had a significantly lower inpatient/30-day mortality rate (adjusted OR 0.81, 95% confidence interval [CI] 0.68 to 0.97), lower rates for 2 perioperative complications (stroke: adjusted OR 0.70, 95% CI 0.57 to 0.86; respiratory failure: adjusted OR 0.80, 95% CI 0.68 to 0.93), and a higher rate of unplanned operation in the same admission (adjusted OR 1.47, 95% CI 1.01 to 2.15). In the matched samples, no difference existed in 3-year mortality (hazard ratio 1.08, 95% CI 0.96 to 1.22), but OPCAB patients had higher rates of subsequent revascularization (hazard ratio 1.55, 95% CI 1.33 to 1.80). The 3-year OPCAB and on-pump survival rates for matched patients were 89.4% and 90.1%, respectively ( P =0.20). For freedom from subsequent revascularization, the respective rates were 89.9% and 93.6% ( P Conclusions— OPCAB is associated with lower in-hospital mortality and complication rates than on-pump CABG, but long-term outcomes are comparable, except for freedom from revascularization, which favors on-pump CABG.

Background Several randomized controlled trials and observational studies have compared outcomes for coronary artery bypass graft (CABG) surgery and drug-eluting stents (DES), but these studies have not thoroughly investigated the relative difference in outcomes by sex. We aimed to compare 3-year outcomes (mortality, mortality/myocardial infarction/stroke, and repeat revascularization) for CABG surgery and percutaneous coronary interventions with DES by sex. Methods A total of 4,532 women (2,266 pairs of CABG and DES patients) and 11,768 men (5,884 pairs) were propensity matched separately using multiple patient risk factors and were compared with respect to 3-year outcomes. Results Both women and men receiving DES had significantly higher mortality rates (adjusted hazard ratio, 1.28; 95% confidence interval, 1.06 to 1.54 and adjusted hazard ratio, 1.22; 95% confidence interval, 1.06 to 1.41, respectively) and myocardial infarction/mortality/stroke rates (adjusted hazard ratio, 1.40; 95% confidence interval, 1.19 to 1.64 and adjusted hazard ratio, 1.36; 95% confidence interval, 1.20 to 1.54, respectively) with DES. The advantage for CABG surgery was also present for several preselected patient subgroups. Men had consistently lower adverse outcome rates than women for both procedures. For example, the mortality rates for CABG and DES for men were 8.0% and 9.1%, compared with respective rates of 11.8% and 13.7% for women. Conclusions For women, the advantage of CABG surgery over DES is very similar to what was found for men, and this advantage persisted for patients with and without high-risk characteristics.

Objectives Our purpose was to develop a risk score to predict in-hospital mortality for percutaneous coronary intervention (PCI) using a statewide population-based PCI registry. Background Risk scores predicting adverse outcomes after PCI have been developed from a single or a small group of hospitals, and their abilities to be generalized to other patient populations might be affected. Methods A logistic regression model was developed to predict in-hospital mortality for PCI using data from 46,090 procedures performed in 41 hospitals in the New York State Percutaneous Coronary Intervention Reporting System in 2002. A risk score was derived from this model and was validated using 2003 data from New York. Results The risk score included nine significant risk factors (age, gender, hemodynamic state, ejection fraction, pre-procedural myocardial infarction, peripheral arterial disease, congestive heart disease, renal failure, and left main disease) that were consistent with other reports. The point values for risk factors range from 1 to 9, and the total risk score ranges from 0 to 40. The observed and recalibrated predicted risks in 2003 were highly correlated for all PCI patients as well as for those in the higher-risk subgroup who suffered myocardial infarctions within 24 h before the procedure. The total risk score for mortality is strongly associated with complication rates and length of stay in the 2003 PCI data. Conclusions The risk score accurately predicted in-hospital death for PCI procedures using future New York data. Its performance in other patient populations needs to be further studied.

Objectives The purpose of this research was to develop a risk index for in-hospital mortality for coronary artery bypass graft (CABG) surgery. Background Risk indexes for CABG surgery are used to assess patients’ operative risk as well as to profile hospitals and surgeons. None has been developed using data from a population-based region in the U.S. for many years. Methods Data from New York’s Cardiac Surgery Reporting System in 2002 were used to develop a statistical model that predicts mortality and to create a risk index based on a relatively small number of patient risk factors. The fit of the index was tested by applying it to another year (2003) of New York data and testing the correspondence of expected and observed mortality rates for each risk score in the index. Results The risk index contains a total of 10 risk factors (age, female gender, hemodynamic state, ejection fraction, pre-procedural myocardial infarction, chronic obstructive pulmonary disease, calcified ascending aorta, peripheral arterial disease, renal failure, and previous open heart operations). The score possible for each variable ranges from 0 to 5, and total risk scores possible range from 0 to 34. The highest score observed for any patient was 22, and 93% of the patients had scores of 8 or lower. When the risk index was applied to another year of New York data with a considerably lower mortality rate, the C-statistic was 0.782. Conclusions The risk index appears to be a valuable tool for predicting patient risk when applied to another year of New York data. It should now be tested against other risk indexes in a variety of geographical regions.

Background— Most studies that are the basis of recommended volume thresholds for percutaneous coronary interventions (PCIs) predate the routine use of stent placement. Methods and Results— Data from New York’s Percutaneous Coronary Interventions Reporting System in 1998 to 2000 (n=107 713) were used to examine the impact of annual hospital volume and annual operator volume on in-hospital mortality, same-day coronary artery bypass graft (CABG) surgery, and same-stay CABG surgery after adjustment for differences in patients’ severity of illness. For a hospital-volume threshold of 400, the odds ratios for low-volume hospitals versus high-volume hospitals were 1.98 (95% CI, 1.17, 3.35) for in-hospital mortality, 2.07 (95% CI, 1.36, 3.15) for same-day CABG surgery, and 1.51 (95% CI, 1.03, 2.21) for same-stay CABG surgery. For an operator-volume threshold of 75, the odds ratios for low-volume versus high-volume operators were 1.65 (95% CI, 1.05, 2.60) for same-day CABG surgery and 1.55 (95% CI, 1.10, 2.18) for same-stay CABG surgery. Operator volume was not significantly associated with mortality. Also, for hospital volumes below 400 and operator volumes below 75, the respective odds of mortality, same-day CABG surgery, and same-stay CABG surgery were 5.92, 4.02, and 3.92 times the odds for hospital volumes of 400 or higher and operator volumes of 75 or higher. Conclusions— Higher-volume operators and hospitals continue to experience lower risk-adjusted PCI outcome rates.

Background— Restriction of volume-based referral for CABG surgery to high-risk patients has been suggested, and earlier studies have reached different conclusions regarding volume-based referral for low-risk patients. Methods and Results— Patients who underwent isolated CABG surgery in New York from 1997 through 1999 (n=57 150) were separated into low-risk and moderate-to-high-risk groups with a predicted probability of in-hospital death of 2% as the cutoff point. The provider volume-mortality relationship was examined for both groups. For annual hospital volume thresholds between 200 and 600 cases, the adjusted ORs of in-hospital mortality for high-volume to low-volume hospitals ranged from 0.45 to 0.77 and were all significant for the low-risk group; for the moderate-to-high-risk group, ORs ranged from 0.62 to 0.91, and most were significant. The number needed to treat at higher-volume hospitals to avoid 1 death was greater for the low-risk group (a range of 114 to 446 versus 37 to 184). As the annual surgeon volume threshold increased from 50 to 150 cases, the ORs for high- to low-volume surgeons increased from 0.43 to 0.74 for the low-risk group; for the moderate-to-high-risk group, ORs ranged from 0.79 to 0.86. Compared with patients treated by surgeons with volumes of Conclusions— For both low-risk and moderate-to-high-risk patients, higher provider volume is associated with lower risk of death.

Background— Studies that are the basis of recommended volume thresholds for CABG surgery are outdated and not reflective of recent advances in the field. This study examines both hospital and surgeon volume-mortality relations for CABG surgery through the use of a population-based clinical data set. Methods and Results— Data from New York’s clinical CABG surgery registry from 1997 to 1999 (total number of procedures, 57 150) were used to examine the individual and combined impact of annual hospital volume and annual surgeon volume on in-hospital mortality rates after adjusting for differences in severity of illness. Significantly lower risk-adjusted mortality rates occurred above all annual hospital volume thresholds between 200 and 800 and above all surgeon volume thresholds between 50 and 200. The number needed to treat (NNT) at higher-volume providers to avoid a death was minimized for a hospital threshold volume of 100 (NNT=50) and a surgeon threshold volume of 50 (NNT=118). The risk-adjusted mortality rate (RAMR) for patients undergoing surgery performed by surgeons with volumes of ≥125 in hospitals with volumes of ≥600 was 1.89%. The RAMR was significantly higher (2.67%) for patients undergoing surgery performed by surgeons with volumes of Conclusions— Higher-volume surgeons and hospitals continue to have lower risk-adjusted mortality rates, and patients undergoing surgery performed by higher-volume surgeons in higher-volume hospitals have the lowest mortality rates.

microRNAs (miRNAs or miRs) are essential in cardiac hypertrophy and in the development of heart failure. In the present study, we aimed to determine whether the restoration of miRNA-455 (miR-455) gene expression in vivo aggravates hypertrophy, but protects against adverse cardiac remodeling induced by pressure overload. Cardiac hypertrophy was induced by left ventricular pressure overload in male mice subjected to transverse aortic constriction (TAC). The mice were randomly selected to receive a tail vein injection of either miR-455 or green fluorescent protein per animal at 1, 8, 15 and 21 days following surgery. Cardiac hypertrophy, function and remodeling were evaluated by echocardiography, catheterization, histological analysis and the examination of the expression of specific genes and cardiac apoptosis. TAC (2 weeks following surgery) resulted in significant cardiac hypertrophy, which was significantly aggravated by treatment with miR-455. However, miR-455 replacement therapy markedly reduced myocardial fibrosis and inhibited apoptosis, suggesting that this therapy can prevent maladaptive ventricular remodeling. miR-455 was also identified and validated to target calreticulin, a protein that is critical for cardiac development. The restoration of miR-455 gene expression may thus be a potential therapeutic strategy to reverse pressure-induced cardiac hypertrophy and prevent maladaptive cardiac remodeling through the regulation of miR-455 at different time points following hypertrophy.

As the most challenging human malignancies, pancreatic cancer is characterized by its insidious symptoms, low rate of surgical resection, high risk of local invasion, metastasis and recurrence, and overall dismal prognosis. Lymphatic metastasis, above all, is recognized as an early adverse event in progression of pancreatic cancer and has been described to be an independent poor prognostic factor. It should be noted that the occurrence of lymphatic metastasis is not a casual or stochastic but an ineluctable and designed event. Increasing evidences suggest that metastasis-initiating cells (MICs) and the microenvironments may act as a double-reed style in this crime. However, the exact mechanisms on how they function synergistically for this dismal clinical course remain largely elusive. Therefore, a better understanding of its molecular and cellular mechanisms involved in pancreatic lymphatic metastasis is urgently required. In this review, we will summarize the latest advances on lymphatic metastasis in pancreatic cancer.

Background A dronedarone utilization study using US MarketScan and InVision Data Mart databases was conducted to estimate the prevalence of the following: (1) dronedarone use in contraindicated patients with worsening heart failure (HF) or hospitalization for HF within 1 month before dronedarone prescription; (2) concomitant prescribing of contraindicated drugs; and (3) recommended creatinine testing after dronedarone initiation among dronedarone users. Methods In this retrospective cohort study, data in the MarketScan database between July 20, 2009, and December 31, 2011, and in the InVision Data Mart database between July 20, 2009, and March 31, 2012, were analyzed. The study population included patients who received ≥1 dronedarone prescription during the study period. The following variables were reported: worsening of or hospitalization for HF, concomitant prescribing of potent cytochrome P450 CYP 3A4 inhibitors or QT-prolonging drugs, and creatinine testing. Results There were 31,408 and 7025 dronedarone users identified in the MarketScan and InVision Data Mart databases, respectively. Approximately 86% to 90% of patients had a diagnosis of atrial fibrillation in each database. In the MarketScan database, 40% were women and 54% were aged ≥65 years. In the InVision Data Mart database, 31% were women and 32% were aged ≥65 years. The corresponding prevalence of worsening or hospitalization for HF was 6.4% (95% CI, 6.2–6.7) and 4.7% (95% CI, 4.2–5.2) in each database, respectively. The corresponding estimates of concomitant prescribing of potent cytochrome P450 CYP 3A4 inhibitors and QT-prolonging drugs within 30 days before initiation or refilling of dronedarone were 2.0% (95% CI, 1.8–2.1) and 10.0% (95% CI, 9.7–10.4), respectively, in the MarketScan database, and 2.3% (95% CI, 2.0–2.7) and 11.2% (95% CI, 10.5–12.0) in the InVision Data Mart database. More than 50% of patients in each database had serum creatinine tests conducted after dronedarone initiation. Conclusions The results of the present analysis based on a long-term follow-up (nearly 3 years) were consistent with the previous findings that dronedarone has mostly been used appropriately in compliance with US prescribing in the target populations.

Several randomized controlled trials and observational studies have compared outcomes of percutaneous coronary interventions (PCIs) with drug-eluting stents (DESs) and coronary artery bypass grafting (CABG), but they have not thoroughly investigated the relative difference in outcomes for patients aged ≥75 years. In this study, a total of 3,864 patients receiving DES and CABG (1,932 CABG-DES pairs) with multivessel coronary disease were propensity matched using multiple patient risk factors and were compared with respect to 3 outcomes (mortality, stroke/myocardial infarction [MI]/mortality, and repeat revascularization) at 2.5 years with a mean follow-up of 18 months. The mortality rates (DES/CABG hazard ratio 1.06, 95% confidence interval 0.87 to 1.30) and the stroke/MI/mortality rates (DES/CABG hazard ratio 1.15, 95% confidence interval 0.97 to 1.38) for the 2 procedures were not significantly different. Repeat revascularization rates were significantly higher for patients who received DESs. In conclusion, older patients experienced similar mortality and stroke/MI/mortality rates for CABG and PCI with DES, although repeat revascularization rates were higher for patients undergoing PCI with DES.

The association between incomplete revascularization (IR) and long-term mortality after stenting in the era of drug-eluting stents is not well understood. In the present study, we test the hypothesis that IR is associated with a greater risk of long-term (5-year) mortality after stenting for multivessel coronary disease. Using data from the Percutaneous Coronary Intervention Reporting System of New York State, 21,767 patients with multivessel disease who underwent stenting during October 2003 to December 2005 were identified. Complete revascularization (CR) was achieved in 6,844 patients (31.4%), and 14,923 patients (68.6%) were incompletely revascularized. The CR and IR patients were propensity matched on a 1:1 ratio on the number of diseased vessels, the presence of total occlusion, type of stents, and the probability of achieving CR estimated using a logistic model with established risk factors as independent variables. Patients were followed for vital status until December 31, 2008 using the National Death Index. Differences in survival between the matched CR and IR patients were compared. Among the 6,511 pairs of propensity-matched patients, the 5-year survival rate for IR was lower compared with CR (79.3% vs 81.4%, p = 0.004), and the risk of death during follow-up was 16% greater for IR compared with CR (hazard ratio 1.16, 95% confidence interval 1.06 to 1.27, p = 0.001). In addition, subgroup analyses demonstrated that the association between IR and long-term mortality was not dependent on major patient risk factors. In conclusion, IR is associated with an increased risk of long-term mortality after stenting for multivessel disease in the era of drug-eluting stents.

Background— No simplified bedside risk scores have been created to predict long-term mortality after coronary artery bypass graft surgery. Methods and Results— The New York State Cardiac Surgery Reporting System was used to identify 8597 patients who underwent isolated coronary artery bypass graft surgery in July through December 2000. The National Death Index was used to ascertain patients' vital statuses through December 31, 2007. A Cox proportional hazards model was fit to predict death after CABG surgery using preprocedural risk factors. Then, points were assigned to significant predictors of death on the basis of the values of their regression coefficients. For each possible point total, the predicted risks of death at years 1, 3, 5, and 7 were calculated. It was found that the 7-year mortality rate was 24.2 in the study population. Significant predictors of death included age, body mass index, ejection fraction, unstable hemodynamic state or shock, left main coronary artery disease, cerebrovascular disease, peripheral arterial disease, congestive heart failure, malignant ventricular arrhythmia, chronic obstructive pulmonary disease, diabetes mellitus, renal failure, and history of open heart surgery. The points assigned to these risk factors ranged from 1 to 7; possible point totals for each patient ranged from 0 to 28. The observed and predicted risks of death at years 1, 3, 5, and 7 across patient groups stratified by point totals were highly correlated. Conclusion— The simplified risk score accurately predicted the risk of mortality after coronary artery bypass graft surgery and can be used for informed consent and as an aid in determining treatment choice.

Objectives To compare 2-year outcomes (mortality, mortality/myocardial infarction (MI), target vessel PCI (TVPCI), and target lesion PCI (TLPCI)) for patients receiving EES and ZES. Background The utilization of drug-eluting coronary stents (DES) among patients undergoing percutaneous coronary interventions (PCI) has increased dramatically in the last decade. Everolimus-eluting stents (EES) and ENDEAVOR zotarolimus eluting stents (ZES) constitute the latest generation of approved DES in the United States, but little is known about their relative effectiveness. Methods New York patients undergoing EES and ZES revascularization without any other type of stent between 7/08 and 12/08 were propensity matched at the hospital level using multiple patient, operator, and hospital characteristics, and matched patients were followed through the end of 2010 to obtain comparative 2-year outcomes. Results A total of 3286 patients were propensity-matched. Patients receiving EES had a significantly lower TVPCI rate (9.0% vs. 11.9%, AHR = 1.31, 95% CI (1.04, 1.65)) and a significantly lower TLPCI rate (6.0% vs. 8.3%, AHR = 1.35, 95% CI (1.02, 1.79)). There was no significant difference between EES and ZES for mortality or MI/mortality. Conclusions There were no significant differences in the hard endpoints of death or MI between patients who received EES versus those who received ZES (ENDEAVOR). Patients with EES experienced lower repeat revascularization rates than patients with ZES at 24 months. © 2012 Wiley Periodicals, Inc.

Background— The survival difference between off-pump and on-pump coronary artery bypass graft surgery for follow-up longer than 5 years is not well-understood. The objective of this study is to examine the difference in 7-year mortality after these 2 procedures. Methods and Results— The state of New York's Cardiac Surgery Reporting System was used to identify the 2640 off-pump and 5940 on-pump patients discharged from July through December 2000. The National Death Index was used to ascertain patients' vital statuses through 2007. A logistic regression model was fit to predict the probability of receiving an off-pump procedure using baseline patient characteristics. Off-pump and on-pump patients were matched with a 1:1 ratio based on the probability of receiving an off-pump procedure. Kaplan-Meier survival curves for the 2 procedures were compared using the propensity-matched data, and the hazard ratio for death for off-pump in comparison with on-pump procedures was obtained. In subgroup analyses, the significance of interactions between type of surgery and baseline risk factors was tested. In this study, 2631 pairs of off-pump and on-pump patients were propensity matched. The 7-year Kaplan-Meier survival rates were 71.2% and 73.4% ( P =0.07) for off-pump and on-pump surgery, respectively. The hazard ratio for death (off-pump versus on-pump) was 1.10 (95% confidence interval: 0.99 to 1.21, P =0.07). No statistical significance was detected for the interaction terms between the type of surgery and a number of different baseline risk factors. Conclusions— The difference in long-term mortality between on-pump and off-pump coronary artery bypass graft surgery is not statistically significant.

Background: Transradial cardiac catheterization has only been used in a small fraction of percutaneous coronary intervention (PCI) procedures in the United States, despite of the evidence that it may be associated with a lower risk of bleeding and mortality following PCI compared to the transfemoral approach. Objective: To evaluate the impact of the transradial approach on adverse outcomes following PCI and its potential of being a process to improve the quality of care for PCI in a single-center practice. Methods: We compared the risks of post-procedural adverse outcomes including in-hospital mortality, bleeding, and vascular complications between the 462 transradial and the 625 transfemoral cases who had undergone PCI procedures between January 2007 and March 2009. The difference in length of stay following PCI between the two entry approaches was also examined. Results: Compared to the transfemoral approach, the transradial cardiac catheterization was associated with significantly lower risk of bleeding (2.60% (12 of 462) vs. 6.08% (38 of 625); adjusted odds ratio (aOR)=0.34, 95% confidence interval (CI): 0.17-0.68, P=0.002) and vascular complications (0% vs. 1.44% (9 of 625), P=0.01). Although the trend was that the transradial approach was associated with lower risk of in-hospital mortality, the difference was not statistically significant (0.87% (4 of 462) vs. 2.24% (14 of 625); aOR=0.55, 95% CI: 0.14-2.10, P=0.38). Transradial patients were more likely to be discharged on the same day of procedure (14.2% vs. 2.2%, P Conclusion: The transradial approach is related to lower risk of bleeding and vascular complications. Introducing this approach to practice could improve the quality of care for PCI.

There is little information on relative survival with follow-up longer than 5 years in patients undergoing coronary artery bypass grafting (CABG) and patients undergoing percutaneous coronary intervention (PCI) with stenting. This study tested the hypothesis that CABG is associated with a lower risk of long-term (8-year) mortality than is stenting with bare-metal stents for multivessel coronary disease.We identified 18,359 patients with multivessel disease who underwent isolated CABG and 13,377 patients who received bare-metal stenting in 1999 to 2000 in New York and followed their vital status through 2007 using the National Death Index (NDI). We matched CABG and stent patients on the number of diseased coronary vessels, proximal left anterior descending (LAD) artery disease, and propensity of undergoing CABG based on numerous patient characteristics and compared survival after the 2 procedures.In the 7,235 pairs of matched patients, the overall 8-year survival rates were 78.0% for CABG and 71.2% for stenting (hazard ratio [HR], 0.68; 95% confidence interval [CI], 0.64 to 0.74; p0.001). For anatomic groups classified by the number of diseased vessels and proximal LAD involvement, the HRs ranged from 0.53 (p0.001) for patients with 3-vessel disease involving proximal LAD artery disease to 0.78 (p = 0.05) for patients with 2-vessel disease but no disease in the LAD artery. A lower risk of death after CABG was observed in all subgroups stratified by a number of baseline risk factors.Coronary artery bypass grafting is associated with a lower risk of death than is stenting with bare metal stents for multivessel coronary disease.

Ventricular premature complexes (VPCs) and atrial premature complexes (APCs) are common findings on routinely obtained electrocardiograms. Despite their common occurrence, the significance of these irregular beats is unclear, especially with regard to risk of sudden cardiac death (SCD). In this study, we examined the prospective relation between baseline VPCs or APCs and SCD, myocardial infarction, and fatal coronary heart disease (CHD) in a population-based sample of subjects from the Atherosclerosis Risk in Communities (ARIC) study excluding participants with known history of CHD or stroke. Baseline examination was conducted from 1987 to 1989, with follow-up data regarding clinical cardiac events collected until December 2002. The total study population was 14,574 subjects. Kaplan-Meier curves and computed univariate and multivariate Cox proportional hazard models were employed to estimate the effect of VPC and APC occurrences on incident cardiac events. During the follow-up period, there were 130 incident cases of SCD, 1,657 incident cases of CHD cases, and 288 cases of fatal CHD. Participants with VPC were 2 times as likely to have SCD (hazard ratio [HR] 2.09, 95% confidence interval [CI] 1.22 to 3.56) compared to those without VPC. Presence of APC was not significantly associated with SCD (HR 1.15, 95% CI 0.56 to 2.39). Compared to subjects without VPC and APC, risk of SCD in subjects with VPC and APC was significantly increased (HR 6.39, 95% CI 2.58 to 15.84). In conclusion, our study shows that subjects with VPCs are significantly more likely to die from SCD, despite not having any known history of cardiovascular disease. This effect appears to be additive when APCs occur concurrently.

Pregnancies in systemic lupus erythematosus (SLE) patients are high risk to both mother and fetus because of increased rates of complications. During the past years, we have treated many cases of SLE patients using autologous peripheral blood stem cell transplantation with good outcome after pregnancy. The rate of maternal hypertension and lupus nephritis was greatly reduced in autologous peripheral blood stem cell transplanted group (n = 11) when compared to non-transplant group (n = 39) (P0.05). In addition, the outcome of lupus flare activity of the mother after delivery is significantly better in transplanted group than that in non-transplanted group (P0.05). Here, we describe two typical cases of long duration (6 years) of remission after successful pregnancy in refractory SLE patients post-autologous peripheral blood stem cell transplantation. Our report demonstrated that peripheral blood stem cell transplantation is safe and effective, thereby could be recommended as prior strategy in refractory SLE patients, especially for those women of child-bearing age who plan for pregnancy.

Limited contemporary information is available on outcomes for patients with unprotected left main coronary artery (LMCA) disease who are revascularized.We examined the relative frequency, severity of illness, and outcomes of stenting and coronary artery bypass graft (CABG) surgery for treating unprotected LMCA disease in New York between January 1, 2000 and December 31, 2004. A total of 16,336 (98.7%) patients who underwent CABG surgery and 212 (1.3%) who underwent stenting were included in this study.Stent patients had higher preprocedural severity of illness (eg, they were older, more likely to be female, and had more comorbidities). A total of 135 stent patients were matched to 135 CABG patients on baseline characteristics identified by a propensity model as predictors of type of procedure received. At the end of follow-up on December 31, 2004, the respective 2-year survival rates were 94.1% and 82.0% (hazard ratio = 0.32, p = 0.005) for the 135 pairs of matched CABG and stent patients. The respective 2-year rates for freedom from subsequent revascularization were 93.7% and 62.7% (hazard ratio = 0.15, p0.001). In the drug-eluting stent era between October 1, 2003 and December 31, 2004, the same trends in mortality (hazard ratio = 0.73, p = 0.69) and repeat revascularization (hazard ratio = 0.10, p = 0.03) were observed among the 56 pairs of matched CABG and drug-eluting stent patients.Most patients with LMCA disease who needed coronary revascularization received CABG surgery; stent patients were sicker. This study found that surgery patients experienced lower risk of long-term death and repeat revascularization. However, more studies comparing these procedures are needed, especially in the drug-eluting stent era.

To the Editor: We read with great interest the recent report by Hannan et al1 on the short-term benefits of off-pump coronary artery bypass graft surgery compared with the standard on-pump approach on in-hospital/30-day mortality and perioperative complication rates. The 3-year follow-up proved comparable outcomes, excluding a lower rate of freedom from revascularization for the off-pump surgery group. The topic is certainly extremely interesting, especially nowadays, when less invasive approaches, such as off-pump coronary surgery and percutaneous coronary interventions, are acquiring dominant roles in the treatment of ischemic heart disease.2 However, we believe that this …

Background A few studies have investigated differences in elective procedure rates across small and medium sized referral regions. The purposes of this study are to investigate differences in revascularizations across 11 entire states and to investigate differences in choice of revascularization procedure (percutaneous coronary intervention (PCI) vs. coronary artery bypass graft (CABG) surgery). Methods Age-sex adjusted rates per 100,000 population who were 20 or older were calculated for PCI, CABG surgery, and total revascularization for each state. Also, the risk-adjusted proportion of revascularized patients who underwent PCI was calculated for each state and differences were compared. Results We found variations in procedures performed per capita of 1.83-fold for PCI, 1.54-fold for CABG surgery, and 1.54-fold for total revascularization. For patients undergoing revascularization of two or more vessels, the age/sex adjusted maximum rate of 224 per 100,000 population over 20 years old in Florida was 53% higher than the minimum rate of 146 in Colorado. Higher catheterization rates per 1,000 Medicare enrollees and higher percent of white patients were significant predictors of higher revascularization rates, and density of specialists was a significant predictor of catheterization rate. The risk-adjusted percentage of revascularized patients with two or more arteries attempted who underwent PCI ranged from 10.4% in Oregon to 29.0% in Iowa. Conclusion There are reasonably large differences among states in total revascularization rates and in type of revascularization among revascularization. These differences appear to be related to practice pattern differences. Future effort should be devoted to understanding the reason for these differences and the impact on patients' health and survival.

Background Numerous studies have developed a "severity score" or "risk index" for short-term mortality associated with coronary artery bypass graft (CABG) surgery, but very few studies have developed risk indices derived from statistical models to predict outcomes for cardiac valve replacement patients. Methods Data from New York's Cardiac Surgery Reporting System in 2001 to 2003 were used to develop statistical models that predict mortality for valve surgery and for valve/CABG surgery. These models were used to develop risk indices based on the type of valve surgery performed and several patient risk factors. The fit of each index was tested by examining the correspondence of expected and observed mortality rates for various risk score ranges using New York data between 1998 and 2000. Results There were a total of 11 risk factors for valve patients without CABG surgery and 12 risk factors for patients with both valve and CABG surgery. Risk factors represented measures of demographics, type of valve surgery, previous open heart surgery, ventricular function, hemodynamic state, and various comorbidities. Possible variable scores ranged from 0 to 7 in the isolated valve model and 0 to 5 in the valve/CABG model. The highest overall risk scores possible for the two models were 49 for isolated valve surgery and 35 for valve/CABG surgery, and the highest scores observed for any patient were 32 and 26, respectively. Conclusions These valve surgery risk indices will enable providers to estimate patients' short-term mortality risk and allow for comparisons of valve surgery outcomes with other regions.

In recent years, several studies in the medical and health service research literature have advocated the use of hierarchical statistical models (multilevel models or random-effects models) to analyze data that are nested (eg, patients nested within hospitals). However, these models are computer-intensive and complicated to perform. There is virtually nothing in the literature that compares the results of standard logistic regression to those of hierarchical logistic models in predicting future provider performance.We sought to compare the ability of standard logistic regression relative to hierarchical modeling in predicting risk-adjusted hospital mortality rates for coronary artery bypass graft (CABG) surgery in New York State.New York State CABG Registry data from 1994 to 1999 were used to relate statistical predictions from a given year to hospital performance 2 years hence.Predicted and observed hospital mortality rates 2 years hence were compared using root mean square errors, the mean absolute difference, and the number of hospitals whose predicted mortality rate data was within a 95% confidence interval around the observed mortality rate.In these data, standard logistic regression performed similarly to hierarchical models, both with and without a second level covariate. Differences in the criteria used for comparison were minimal, and when the differences could be statistically tested no significant differences were identified.It is instructive to compare the predictive abilities of alternative statistical models in the process of assessing their relative performance on a specific database and application.