Comparison of combination methods to create calibrated ensemble forecasts for seasonal influenza in the U.S.

The characteristics of influenza seasons vary substantially from year to year, posing challenges for public health preparation and response. Influenza forecasting is used to inform seasonal outbreak response, which can in turn potentially reduce the impact of an epidemic. The United States Centers for Disease Control and Prevention, in collaboration with external researchers, has run an annual prospective influenza forecasting exercise, known as the FluSight challenge. Uniting theoretical results from the forecasting literature with domain-specific forecasts from influenza outbreaks, we applied parametric forecast combination methods that simultaneously optimize model weights and calibrate the ensemble via a beta transformation and made adjustments to the methods to reduce their complexity. We used the beta-transformed linear pool, the finite beta mixture model, and their equal weight adaptations to produce ensemble forecasts retrospectively for the 2016/2017, 2017/2018, and 2018/2019 influenza seasons in the U.S. We compared their performance to methods that were used in the FluSight challenge to produce the FluSight Network ensemble, namely the equally weighted linear pool and the linear pool. Ensemble forecasts produced from methods with a beta transformation were shown to outperform those from the equally weighted linear pool and the linear pool for all week-ahead targets across in the test seasons based on average log scores. We observed improvements in overall accuracy despite the beta-transformed linear pool or beta mixture methods' modest under-prediction across all targets and seasons. Combination techniques that explicitly adjust for known calibration issues in linear pooling should be considered to improve probabilistic scores in outbreak settings.

Association of Statin Use and Mortality After Transcatheter Aortic Valve Replacement.

Background Statins may reduce mortality after transcatheter aortic valve replacement (TAVR) through prevention of atherosclerotic events or pleiotropic effects. However, the competing mortality risks in TAVR patients may dilute any positive effect of statins. We sought to understand the association of statin use with post-TAVR mortality. Methods and Results We included high- or intermediate-surgical risk patients who underwent TAVR as a part of the PARTNER (Placement of Aortic Transcatheter Valves) II and Sapien 3 trials and registries. Outcomes included 2-year all-cause, cardiovascular, and noncardiovascular mortality. We used propensity score matching to generate matched pairs between those discharged on a statin and those not on a statin after TAVR. Bias was explored with falsification end points (urinary infection, hip fracture). Among 3956 patients who underwent TAVR, we matched 626 patients on a statin with 626 patients not on a statin at discharge. Among matched patients, statin use was associated with lower risk of all-cause (hazard ratio [HR] 0.65, 95% CI 0.49-0.87, P=0.001), cardiovascular (HR 0.66, 95% CI 0.46-0.96, P=0.030), and noncardiovascular mortality (HR 0.64, 95% CI 0.44-0.99, P=0.045) compared with no statin use. The survival curves diverged within 3 months and continued to separate over a median follow-up of 2.1 years. The falsification end points were similar among groups (urinary infection, P=0.66; hip fracture, P=0.64). Conclusions In an observational, propensity-matched analysis of TAVR patients, statin use was associated with lower rates of cardiovascular and noncardiovascular mortality compared with no statin use. Given the early emergence of the apparent protective effect of statins, this result may be driven either by pleiotropic effects or by residual confounding despite propensity-matching methodology.

Impact of Short-Term Complications on Mortality and Quality of Life After Transcatheter Aortic Valve Replacement.

OBJECTIVES: The aim of this study was to examine the independent association of short-term complications of transcatheter aortic valve replacement (TAVR) with survival and quality of life at 1 year. BACKGROUND: Prior studies have examined the mortality and cost implications of various complications of TAVR. However, many of these complications may primarily affect patients' quality of life after TAVR, which has not been previously studied. METHODS: Among patients at intermediate or high surgical risk who underwent TAVR as part of the PARTNER (Placement of Aortic Transcatheter Valve) 2 studies and survived 30 days, the association between complications within the 30 days after TAVR and mortality and quality of life at 1 year was examined. Quality of life was assessed using the Kansas City Cardiomyopathy Questionnaire and the Short-Form 12. Complications assessed included major and minor stroke, life-threatening and major bleeding, vascular injury, stage 3 acute kidney injury, new pacemaker implantation, and mild and moderate or severe paravalvular leak (PVL). Multivariable models that included all complications as well as baseline clinical factors were used to examine the independent association of each complication with outcomes. RESULTS: Among 3,763 TAVR patients, major stroke and stage 3 acute kidney injury were associated with markedly increased risk for 1-year mortality, with adjusted hazard ratios of 5.4 (95% confidence interval [CI]: 3.1 to 9.5) and 4.9 (95% CI: 2.7 to 8.8), respectively, as well as poorer quality of life among survivors (reductions in 1-year Kansas City Cardiomyopathy Questionnaire overall summary score of 15.1 points [95% CI: 24.8 to 5.3 points] and 14.7 points [95% CI: 25.6 to 3.8 points], respectively). Moderate or severe PVL, life-threatening bleeding, and major bleeding were each associated with a more modest increase in mortality and decrement in quality of life, whereas mild PVL was associated with a small decrease in quality of life. After adjusting for baseline characteristics and other complications, need for a new pacemaker, minor stroke, and vascular injury were not independently associated with poor outcomes. CONCLUSIONS: Among patients undergoing TAVR, similar events are associated with increased mortality and impaired quality of life at 1 year. These results suggest that despite considerable progress, efforts to further reduce stroke, acute kidney injury, bleeding, and moderate or severe PVL are likely to yield important clinical benefits and remain key targets for device iteration and procedural improvement.

Predictors of Left Ventricular Remodeling After Myocardial Infarction in Patients With a Patent Infarct Related Coronary Artery After Percutaneous Coronary Intervention (from the Post-Myocardial Infarction Remodeling Prevention Therapy [PRomPT] Trial).

Left ventricular (LV) remodeling after myocardial infarction (MI) is a strong predictor of heart failure and mortality. The predictors of long-term remodeling after MI have been incompletely studied. We therefore examined the correlates of LV remodeling in patients with large ST-segment elevation myocardial infarction and a patent infarct artery after percutaneous 2coronary intervention (PCI) from the randomized Post-Myocardial Infarction Remodeling Prevention Therapy trial. Peri-infarct pacing had a neutral effect on long-term remodeling in patients with large first MI. The present analysis includes 109 patients in whom an open artery was restored after PCI, and in whom LV end-diastolic volume (LVEDV) at baseline and 18 months was assessed by transthoracic echocardiography. Multivariable models were fit to identify the independent predictors of LVEDV at baseline and 18 months. By multivariable analysis, male sex (p = 0.004) and anterior MI location (p = 0.03) were independently associated with baseline LVEDV. The following variables were independent predictors of increased LVEDV at 18 months: younger age (p = 0.01), male sex (p = 0.03), peak creatine phosphokinase (p = 0.03), shorter time from MI to baseline transthoracic echocardiography (p = 0.04), baseline LVEDV (p < 0.0001), and lack of statin use (p = 0.03). In conclusion, patients with large MI and an open infarct artery after PCI, anterior MI location, and male sex were associated with greater baseline LVEDV, but MI location was not associated with 18-month LVEDV. In contrast, younger age, peak creatine phosphokinase, male sex, baseline LVEDV, and lack of statin use were associated with long-term LV remodeling.

Reply & Supply: Efficient crowdsourcing when workers do more than answer questions.

Crowdsourcing works by distributing many small tasks to large numbers of workers, yet the true potential of crowdsourcing lies in workers doing more than performing simple tasks-they can apply their experience and creativity to provide new and unexpected information to the crowdsourcer. One such case is when workers not only answer a crowdsourcer's questions but also contribute new questions for subsequent crowd analysis, leading to a growing set of questions. This growth creates an inherent bias for early questions since a question introduced earlier by a worker can be answered by more subsequent workers than a question introduced later. Here we study how to perform efficient crowdsourcing with such growing question sets. By modeling question sets as networks of interrelated questions, we introduce algorithms to help curtail the growth bias by efficiently distributing workers between exploring new questions and addressing current questions. Experiments and simulations demonstrate that these algorithms can efficiently explore an unbounded set of questions without losing confidence in crowd answers.

Impact of TCFA on Unanticipated Ischemic Events in Medically Treated Diabetes Mellitus: Insights From the PROSPECT Study.

OBJECTIVES: This study sought to investigate the relationship between thin-cap fibroatheromas (TCFAs) on major adverse cardiac events (MACEs) arising from medically treated nonculprit lesions (NCLs) in patients with acute coronary syndromes (ACS) with and without diabetes mellitus (DM). BACKGROUND: MACEs occur frequently in patients with DM and ACS. The impact of plaque composition on subsequent MACEs in DM patients with ACS is unknown. METHODS: In the PROSPECT (Providing Regional Observations Study Predictors of Events in the Coronary Tree) study, using 3-vessel radiofrequency intravascular ultrasound, we analyzed the incidence of NCL-MACE in 2 propensity-matched groups according to the presence of DM and TCFA. RESULTS: Among 697 patients, 119 (17.7%) had DM. The 3-year total MACE rate (29.4% vs. 18.8%; p = 0.01) was significantly higher in patients with versus without DM, driven by a higher rate of NCL-MACE in DM (18.7% vs. 10.4%; p = 0.02). Propensity score matching generated 2 balanced groups with and without DM of 82 patients each. Among DM patients, the presence of ≥1 TCFA was associated with higher NCL-MACE at 3 years (27.8% vs. 8.9% in patients without a TCFA, hazard ratio: 3.56; 95% confidence interval: 0.98 to 12.96; p = 0.04). DM patients without a TCFA had a similar 3-year rate of NCL-MACE as patients without DM (8.9% vs. 8.9%; hazard ratio: 1.09; 95% confidence interval: 0.27 to 4.41; p = 0.90). CONCLUSIONS: ACS patients with DM and ≥1 TCFA have a high rate of NCL-MACE at 3 years. In contrast, the prognosis of ACS patients with DM but no TCFAs is favorable and similar to patients without DM.

Robustness of spatial micronetworks.

Power lines, roadways, pipelines, and other physical infrastructure are critical to modern society. These structures may be viewed as spatial networks where geographic distances play a role in the functionality and construction cost of links. Traditionally, studies of network robustness have primarily considered the connectedness of large, random networks. Yet for spatial infrastructure, physical distances must also play a role in network robustness. Understanding the robustness of small spatial networks is particularly important with the increasing interest in microgrids, i.e., small-area distributed power grids that are well suited to using renewable energy resources. We study the random failures of links in small networks where functionality depends on both spatial distance and topological connectedness. By introducing a percolation model where the failure of each link is proportional to its spatial length, we find that when failures depend on spatial distances, networks are more fragile than expected. Accounting for spatial effects in both construction and robustness is important for designing efficient microgrids and other network infrastructure.

The association between the extent of coronary artery disease and major bleeding events after percutaneous coronary intervention: from the ACUITY trial.

OBJECTIVE: We sought to evaluate the relation between the extent of coronary artery disease (CAD) and bleeding risk in patients undergoing percutaneous coronary intervention (PCI) for non-ST segment elevation acute coronary syndrome (NSTEACS). BACKGROUND: Patients with severe CAD undergoing PCI for NSTEACS are at high risk for recurrent adverse events. Hemorrhagic events after PCI are associated with high rates of morbidity and mortality. Despite sharing many common risk factors, the relationship between the extent of CAD and bleeding after PCI remains understudied. METHODS: The SYNTAX score (SS) was used to quantify the extent and severity of CAD. We stratified 2627 patients from the ACUITY PCI cohort into SS groups based on score tertiles from the ACUITY trial (<7, 7-12, and >12). Thirty-day major bleeding rates were determined for each group. RESULTS: When stratified by ACUITY tertiles, 30-day major bleeding rates were significantly greater in the highest SS tertile (>12) than in the intermediate and lowest tertiles (P<.01). By multivariable analysis, the SS (by augmentation of 1 point) remained independently associated with 30-day major bleeding (hazard ratio = 1.03; 95% confidence interval, 1.01-1.04; P<.01). CONCLUSION: The results of this large-scale study suggest that in addition to its previously described association with adverse ischemic events, the extent of CAD, as assessed by the SS, was independently associated with major bleeding after PCI for NSTEACS.

Femoral vascular closure device use, bivalirudin anticoagulation, and bleeding after primary angioplasty for STEMI: results from the HORIZONS-AMI trial.

OBJECTIVE: To assess the relationship of femoral vascular closure device (VCD) use to bleeding and ischemic events in patients undergoing primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) via different anticoagulation strategies. BACKGROUND: It is unknown whether femoral VCD reduce major bleeding after primary PCI for STEMI using bivalirudin anticoagulation. METHODS: We compared VCD-treated patients with propensity-matched controls in the HORIZONS-AMI trial with respect to net adverse clinical events (NACE), defined as the composite of major bleeding unrelated to coronary artery bypass graft surgery (CABG) and major adverse cardiac events (comprised of death, reinfarction, ischemia-driven target vessel revascularization, and stroke), at 30 days and 1 year. RESULTS: Among 3,602 patients enrolled in HORIZONS-AMI, 2,948 underwent primary PCI via femoral arterial access and 896 (30%) received VCDs, of whom 642 were included in our model along with 642 propensity-matched controls. At 30 days, VCD-treated patients had significantly less NACE (6.7% vs. 10.8%, HR: 0.61, 95% CI: 0.42-0.89, P = 0.009), driven by a lower rate of non-CABG related major bleeding (5.0% vs. 8.1%, HR: 0.61, 95% CI: 0.39-0.94, P = 0.02). Bleeding reduction was maintained at one year and consistent in magnitude regardless of randomization to bivalirudin or unfractionated heparin plus a glycoprotein IIb/IIIa inhibitor (P for interaction = 0.84). CONCLUSION: In patients undergoing transfemoral primary PCI for STEMI, VCD use was associated with significantly lower non-CABG major bleeding irrespective of anticoagulation strategy.

Clinical profile and impact of family history of premature coronary artery disease on clinical outcomes of patients undergoing primary percutaneous coronary intervention for ST-elevation myocardial infarction: analysis from the HORIZONS-AMI Trial.

BACKGROUND/PURPOSE: Family history of coronary artery disease (CAD) is a well-established risk factor of future cardiovascular events. The authors sought to examine the relationship between family history of CAD and clinical profile and prognosis of patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). MATERIALS/METHODS: Baseline features and clinical outcomes at 30 days and at 3 years from 3601 patients with STEMI enrolled in the HORIZONS-AMI trial were compared in patients with and without family history of premature CAD, which was present in 1059 patients (29.4%). RESULTS: These patients were younger (median 56.7 vs. 62.1years, P<0.0001) and more often current smokers (52.4% vs. 43.5%, P<0.0001), had more dyslipidemia (47.7% vs. 41.1%, P=0.0003), less diabetes mellitus (14.1% vs. 17.5%, P=0.01) and had shorter symptom onset to balloon times (median 213 vs. 225 min, P=0.02). Patients with a family history of premature CAD had higher rates of final TIMI 3 flow (93.8% vs. 90.6%, P=0.002), and myocardial blush grade 2 or 3 (83.2% vs. 78.0% P=0.0008), and fewer procedural complications. Although the unadjusted 30-day and 3-year mortality rates were lower in patients with a family history of premature CAD (1.8% vs. 3.0%, P=0.046 and 4.8% vs. 7.7%, P=0.002, respectively), by multivariable analysis the presence of a family history of premature CAD was not an independent predictor of death at 3 years (HR [95%CI]=1.00 [0.70, 1.44], P=0.98). CONCLUSIONS: A family history of premature CAD is not an independent predictor of higher mortality.

Stenting for ST-segment elevation myocardial infarction is associated with less neointimal hyperplasia in the pooled IVUS analysis from HORIZONS-AMI and the TAXUS IV and V and ATLAS workhorse, long lesion, and direct stent studies.

OBJECTIVE: To investigate the difference in neointimal hyperplasia (NIH) between ST-segment elevation myocardial infarction (STEMI), stable angina pectoris (SAP), and unstable angina pectoris (UAP). PATIENTS AND METHODS: From formal core laboratory intravascular ultrasound substudies, we compared NIH after paclitaxel-eluting stents (PES) or bare metal stents (BMS) in STEMI lesions from HORIZONS-AMI trial with SAP and UAP lesions from TAXUS IV, V, and ATLAS studies. RESULTS: At follow-up, %NIH at the minimum lumen area (MLA) site was less in STEMI (n=212) than in UAP (n=233) and SAP (n=440) lesions treated with PES (19.6 vs. 26.2 vs. 25.0%, P=0.002; all intravascular ultrasound data shown as least-square means in abstract) and less in STEMI (n=66) than in UAP (n=72) and SAP (n=143) lesions treated with BMS (34.0 vs. 26.7 vs. 45.5%, P=0.0003). As a result, MLA at follow-up was larger in STEMI than in UAP and SAP lesions treated with PES (5.9 vs. 5.2 vs. 5.0 mm, P<0.0001) or treated with BMS (5.1 vs. 4.3 vs. 4.0 mm, P=0.002). Net volume obstruction ([NIH/stent volume]×100) at follow-up was significantly less in STEMI than in UAP and SAP lesions treated with PES (7.8 vs. 13.4 vs. 13.4%, P<0.0001) or BMS (20.6 vs. 28.5 vs. 32.1%, P<0.0001). Multivariate linear regression analysis showed that STEMI was correlated independently and inversely with net volume obstruction compared with SAP (regression coefficient -6.99, P<0.0001) or UAP (regression coefficient -6.29, P<0.0001). CONCLUSION: Implantation of PES or BMS in STEMI compared with UAP and SAP was associated with less NIH.

Early regression of severe left ventricular hypertrophy after transcatheter aortic valve replacement is associated with decreased hospitalizations.

OBJECTIVES: This study sought to examine the relationship between left ventricular mass (LVM) regression and clinical outcomes after transcatheter aortic valve replacement (TAVR). BACKGROUND: LVM regression after valve replacement for aortic stenosis is assumed to be a favorable effect of LV unloading, but its relationship to improved clinical outcomes is unclear. METHODS: Of 2,115 patients with symptomatic aortic stenosis at high surgical risk receiving TAVR in the PARTNER (Placement of Aortic Transcatheter Valves) randomized trial or continued access registry, 690 had both severe LV hypertrophy (left ventricular mass index [LVMi] ≥ 149 g/m(2) men, ≥ 122 g/m(2) women) at baseline and an LVMi measurement at 30-day post-TAVR follow-up. Clinical outcomes were compared for patients with greater than versus lesser than median percentage change in LVMi between baseline and 30 days using Cox proportional hazard models to evaluate event rates from 30 to 365 days. RESULTS: Compared with patients with lesser regression, patients with greater LVMi regression had a similar rate of all-cause mortality (14.1% vs. 14.3%, p = 0.99), but a lower rate of rehospitalization (9.5% vs. 18.5%, hazard ratio [HR]: 0.50, 95% confidence interval [CI]: 0.32 to 0.78; p = 0.002) and a lower rate of rehospitalization specifically for heart failure (7.3% vs. 13.6%, p = 0.01). The association with a lower rate of rehospitalization was consistent across subgroups and remained significant after multivariable adjustment (HR: 0.53, 95% CI: 0.34 to 0.84; p = 0.007). Patients with greater LVMi regression had lower B-type natriuretic peptide (p = 0.002) and a trend toward better quality of life (p = 0.06) at 1-year follow-up than did those with lesser regression. CONCLUSIONS: In high-risk patients with severe aortic stenosis and severe LV hypertrophy undergoing TAVR, those with greater early LVM regression had one-half the rate of rehospitalization over the subsequent year compared to those with lesser regression.

Body mass index and acute and long-term outcomes after acute myocardial infarction (from the Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction Trial).

The clinical outcome of acute cardiovascular events may be more favorable in patients with a high body mass index (BMI), although obesity increases the risk for cardiovascular diseases. The authors sought to define the association between BMI and acute and long-term outcome of patients presenting within 12 hours of ST-segment myocardial infarction (STEMI) in a large multinational cohort. A total of 3,579 patients enrolled in the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction trial were stratified according to BMI quartiles: <24.5, 24.5 to <27.1, 27.1 to 30.1, and >30.1 kg/m(2) (quartiles 1, 2, 3, and 4, respectively). Death, myocardial reinfarction, ischemia-driven target vessel revascularization, stroke, and noncoronary artery bypass grafting-related major bleeding events were centrally adjudicated for the acute, 30 days, and yearly follow-up. Patients with a BMI in the highest quartile were younger than patients in the lower BMI quartiles and more frequently had hypertension, hyperlipidemia, and diabetes mellitus. Complete occlusions and noncalcified lesions were more common in patients with a high BMI. In-hospital mortality decreased with increasing BMI due to lower cardiac mortality (2.9%, 2.3%, 1.2%, and 1.0% for quartiles 1, 2, 3, and 4, respectively, p <0.05). Out-of-hospital 3-year mortality was also lower in higher-weight patients due to lower noncardiac mortality (4.2%, 2.6%, 2.3%, and 1.7% for quartiles 1 to 4, respectively, p = 0.01). After adjustment for covariates, BMI was no longer predictive of acute or long-term mortality after STEMI. In conclusion, as BMI increases, patients have a more extensive adjusted cardiovascular risk profile and disease burden and premature STEMI onset but similar adjusted acute and long-term outcomes.

Impact of coronary lesion complexity on drug-eluting stent outcomes in patients with and without diabetes mellitus: analysis from 18 pooled randomized trials.

OBJECTIVES: The aim of this study was to investigate whether baseline lesion complexity affects drug-eluting stent (DES) outcomes according to diabetic status. BACKGROUND: Previous studies have reported conflicting results regarding DES safety and efficacy in patients with and without diabetes mellitus (DM). METHODS: Patient-level data from 18 prospective randomized trials were pooled. DES treatment outcomes in patients with versus without DM were analyzed in 2 propensity score-matched groups further stratified according to lesion complexity (American College of Cardiology and American Heart Association class A/B1 vs. B2/C). Remaining baseline differences were adjusted for by multivariate analysis. RESULTS: DM was present in 3,467 of 18,441 patients (18.8%). DM was a predictor of 1-year repeat revascularization (target lesion revascularization: hazard ratio: 1.34; 95% confidence interval: 1.05 to 1.70; target vessel revascularization: hazard ratio: 1.40; 95% confidence interval: 1.15 to 1.72) and cardiac death or myocardial infarction (hazard ratio: 1.40; 95% confidence interval: 1.09 to 1.81). Rates of target lesion and target vessel revascularization were significantly higher in patients with versus those without DM with type B2/C lesions (8.0% vs. 4.5% and 10.6% vs. 5.9%, respectively, p < 0.0001 for both), but not in patients with only type A/B1 lesions (4.6% vs. 4.8%, p = 0.87, and 7.4% vs. 6.8%, p = 0.47, respectively), with a significant interaction between DM and lesion type observed for both endpoints (p = 0.01 and p = 0.02, respectively). No interaction was observed for death or myocardial infarction (p = 0.28). CONCLUSIONS: In the DES era, patients with DM remain at increased risk for cardiac death or myocardial infarction. However, DM is a risk factor for repeat revascularization only in those patients with complex lesions; patients with DM and noncomplex lesions have similar rates of 1-year freedom from repeat revascularization as do patients without DM.

Sex-related differences in outcomes after transcatheter or surgical aortic valve replacement in patients with severe aortic stenosis: Insights from the PARTNER Trial (Placement of Aortic Transcatheter Valve).

OBJECTIVES: This study sought to examine sex-specific differences in outcomes after surgical aortic valve replacement (SAVR) or transcatheter aortic valve replacement (TAVR) in high-risk patients with severe aortic stenosis. BACKGROUND: The PARTNER (Placement of Aortic Transcatheter Valve) trial demonstrated similar 2-year survival with SAVR or TAVR for high-risk patients, but sex-specific outcomes are unknown. METHODS: In all, 699 patients (300 female) were randomly assigned 1:1 to either SAVR or TAVR with a balloon expandable pericardial tissue valve. Baseline characteristics and 2-year outcomes of TAVR versus SAVR were compared among males and females. RESULTS: Baseline characteristics differed between the sexes. Despite higher Society of Thoracic Surgeons mortality risk scores (11.9 vs. 11.6; p = 0.05), female patients had lower prevalence of coronary artery disease (64.4% vs. 83.7%), prior coronary artery bypass graft surgery (19.8% vs. 61.2%), peripheral vascular disease (36.4% vs. 46.9%), diabetes mellitus (35.6% vs. 45.6%), and elevated creatinine (11.7% vs. 23.9%). Among female patients, procedural mortality trended lower with TAVR versus SAVR (6.8% vs. 13.1%; p = 0.07) and was maintained throughout follow-up (hazard ratio [HR]: 0.67; 95% confidence interval [CI]: 0.44 to 1.00; p = 0.049), driven by the transfemoral arm (HR: 0.55; 95% CI: 0.32 to 0.93; p = 0.02). Among male patients, although procedural mortality was lower with TAVR (6% vs. 12.1%; p = 0.03), there was no overall survival benefit (HR: 1.15; 95% CI: 0.82 to 1.61; p = 0.42). CONCLUSIONS: In this retrospective subanalysis of high-risk, symptomatic aortic stenosis patients in the PARTNER trial, female subjects had lower late mortality with TAVR versus SAVR. This was especially true among patients suitable for transfemoral access and suggests that TAVR may be preferred over surgery for high-risk female patients. A randomized, controlled trial conducted specifically in female patients is necessary to properly study differences in mortality between treatment modalities. (THE PARTNER TRIAL: Placement of AoRTic TraNscathetER Valve Trial; NCT00530894).

A clinical and pathologic comparison between stage-matched endometrial intraepithelial carcinoma and uterine serous carcinoma: is there a difference?

Endometrial intraepithelial carcinoma (EIC) is a rare pathologic variant of uterine serous carcinoma (USC). Our aim is to distinguish patterns of clinic-pathologic outcomes in patients with EIC and USC for disease limited to the endometrium (stage 1A) as well as with distant metastasis (stage 4B). Surgically staged patients were retrospectively identified and relevant variables were extracted and compared. Kaplan-Meier was used to generate the survival data. More USC (n = 29) exhibited lymphovascular invasion (stage 4, P = .01) and expressed higher levels of estrogen receptor-α than EIC (P = .0009 and .063 for stages 1 and 4, respectively). The survival is comparable, with 1 recurrence in each group for stage 1A disease. For stage 4 EIC and USC, the progression-free survival (14 vs10 months) and overall survival (19 vs 20 months) are similar to what is previously published. In conclusion, EIC, whether limited to the endometrium, or widely metastatic, imparts similar outcomes and should be treated comparably with stage-matched USC.

Transcatheter versus surgical aortic valve replacement in patients with diabetes and severe aortic stenosis at high risk for surgery: an analysis of the PARTNER Trial (Placement of Aortic Transcatheter Valve).

OBJECTIVES: The goal of this study was to determine whether a less-invasive approach to aortic valve replacement (AVR) improves clinical outcomes in diabetic patients with aortic stenosis (AS). BACKGROUND: Diabetes is associated with increased morbidity and mortality after surgical AVR for AS. METHODS: Among treated patients with severe symptomatic AS at high risk for surgery in the PARTNER (Placement of Aortic Transcatheter Valve) trial, we examined outcomes stratified according to diabetes status of patients randomly assigned to receive transcatheter or surgical AVR. The primary outcome was all-cause mortality at 1 year. RESULTS: Among 657 patients enrolled in PARTNER who underwent treatment, there were 275 patients with diabetes (145 transcatheter, 130 surgical). There was a significant interaction between diabetes and treatment group for 1-year all-cause mortality (p = 0.048). Among diabetic patients, all-cause mortality at 1 year was 18.0% in the transcatheter group and 27.4% in the surgical group (hazard ratio: 0.60 [95% confidence interval: 0.36 to 0.99]; p = 0.04). Results were consistent among patients treated via transfemoral or transapical routes. In contrast, among nondiabetic patients, there was no significant difference in all-cause mortality at 1 year (p = 0.48). Among diabetic patients, the 1-year rates of stroke were similar between treatment groups (3.5% transcatheter vs. 3.5% surgery; p = 0.88), but the rate of renal failure requiring dialysis >30 days was lower in the transcatheter group (0% vs. 6.1%; p = 0.003). CONCLUSIONS: Among patients with diabetes and severe symptomatic AS at high risk for surgery, this post-hoc stratified analysis of the PARTNER trial suggests there is a survival benefit, no increase in stroke, and less renal failure from treatment with transcatheter AVR compared with surgical AVR. (The PARTNER Trial: Placement of AoRTic TraNscathetER Valve Trial; NCT00530894).

Bleeding complications after surgical aortic valve replacement compared with transcatheter aortic valve replacement: insights from the PARTNER I Trial (Placement of Aortic Transcatheter Valve).

OBJECTIVES: This study sought to identify the incidence, predictors, and prognostic impact of bleeding complications (BC) after surgical aortic valve replacement (SAVR) compared with transcatheter aortic valve replacement (TAVR). BACKGROUND: Bleeding complications after SAVR and TAVR are frequent and may be associated with an unfavorable prognosis. METHODS: In the randomized controlled PARTNER (Placement of Aortic Transcatheter Valve) I trial, 657 patients from cohort A (operable high risk) were randomly assigned to SAVR or TAVR (transfemoral [TF] if iliofemoral access was suitable or transapical [TA] if not) and received the designated treatment. First-generation Edwards SAPIEN valves and delivery systems (Edwards Lifesciences, Irvine, California) were used for TAVR, through a 22- or 24-F sheath. The 30-day rates of major BC (modified Valve Academic Research Consortium definitions), predictors of BC, and their association with 1-year mortality were assessed. RESULTS: A total of 71 (22.7%), 27 (11.3%), and 9 (8.8%) patients had major BC within 30 days of the procedure after SAVR, TF-TAVR, and TA-TAVR, respectively (p < 0.0001). SAVR was associated with a significantly higher 30-day rate of transfusion (17.9%) than either TF-TAVR (7.1%) or TA-TAVR (4.8%; p < 0.0001). Independent predictors of major BC were the occurrence of major vascular complications and use of intraprocedural hemodynamic support among TF-TAVR patients, severe procedural complications requiring conversion to open surgery among TA-TAVR patients, and the presence of low hemoglobin at baseline among SAVR patients. Major BC was identified as the strongest independent predictor of 1-year mortality among the full cohort. However, risk-adjusted analyses demonstrated a significant interaction between BC and treatment strategy with respect to mortality, suggesting that BC after SAVR have a greater impact on prognosis than after TAVR. CONCLUSIONS: Among high-risk aortic stenosis patients enrolled in the PARTNER I randomized trial, BC were more common after SAVR than after TAVR and were also associated with a worse long-term prognosis. (THE PARTNER TRIAL: Placement of AoRTic TraNscathetER Valve Trial; NCT00530894).

Prediction of 1-year mortality in patients with acute coronary syndromes undergoing percutaneous coronary intervention: validation of the logistic clinical SYNTAX (Synergy Between Percutaneous Coronary Interventions With Taxus and Cardiac Surgery) score.

OBJECTIVES: This study sought to validate the Logistic Clinical SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score in patients with non-ST-segment elevation acute coronary syndromes (ACS), in order to further legitimize its clinical application. BACKGROUND: The Logistic Clinical SYNTAX score allows for an individualized prediction of 1-year mortality in patients undergoing contemporary percutaneous coronary intervention. It is composed of a "Core" Model (anatomical SYNTAX score, age, creatinine clearance, and left ventricular ejection fraction), and "Extended" Model (composed of an additional 6 clinical variables), and has previously been cross validated in 7 contemporary stent trials (>6,000 patients). METHODS: One-year all-cause death was analyzed in 2,627 patients undergoing percutaneous coronary intervention from the ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trial. Mortality predictions from the Core and Extended Models were studied with respect to discrimination, that is, separation of those with and without 1-year all-cause death (assessed by the concordance [C] statistic), and calibration, that is, agreement between observed and predicted outcomes (assessed with validation plots). Decision curve analyses, which weight the harms (false positives) against benefits (true positives) of using a risk score to make mortality predictions, were undertaken to assess clinical usefulness. RESULTS: In the ACUITY trial, the median SYNTAX score was 9.0 (interquartile range 5.0 to 16.0); approximately 40% of patients had 3-vessel disease, 29% diabetes, and 85% underwent drug-eluting stent implantation. Validation plots confirmed agreement between observed and predicted mortality. The Core and Extended Models demonstrated substantial improvements in the discriminative ability for 1-year all-cause death compared with the anatomical SYNTAX score in isolation (C-statistics: SYNTAX score: 0.64, 95% confidence interval [CI]: 0.56 to 0.71; Core Model: 0.74, 95% CI: 0.66 to 0.79; Extended Model: 0.77, 95% CI: 0.70 to 0.83). Decision curve analyses confirmed the increasing ability to correctly identify patients who would die at 1 year with the Extended Model versus the Core Model versus the anatomical SYNTAX score, over a wide range of thresholds for mortality risk predictions. CONCLUSIONS: Compared to the anatomical SYNTAX score alone, the Core and Extended Models of the Logistic Clinical SYNTAX score more accurately predicted individual 1-year mortality in patients presenting with non-ST-segment elevation acute coronary syndromes undergoing percutaneous coronary intervention. These findings support the clinical application of the Logistic Clinical SYNTAX score.

Impact of bivalirudin and paclitaxel-eluting stents on outcomes in patients undergoing primary percutaneous coronary intervention of the left anterior descending artery.

Patients with ST elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) of the left anterior descending artery (LAD) are at increased risk for cardiovascular events compared with patients undergoing non-LAD PCI. We assessed the impact of bivalirudin and paclitaxel-eluting stenting (PES) in patients with STEMI who underwent LAD PCI. In the HORIZONS-AMI trial, 1,445 patients had LAD PCI and 1,884 patients had non-LAD PCI. The 3-year composite rates of death, reinfarction, stroke, or ischemia-driven target vessel revascularization were significantly higher in patients who underwent LAD PCI compared with non-LAD PCI (24.0% vs 20.6%, hazard ratio [HR] 1.20, 95% confidence interval [CI] 1.04 to 1.39, p = 0.013), driven by a statistically significant increase in cardiac death (5.4% vs 2.7%, HR 2.00, 95% CI 1.40 to 2.86, p = 0.001). For patients who underwent LAD PCI, treatment with bivalirudin resulted in significantly lower rates of cardiac death (3.8% vs 6.8%, HR 0.55, 95% CI 0.34 to 0.89, p = 0.01), reinfarction (5.3% vs 9.5%, HR 0.55, 95% CI 0.37 to 0.83, p = 0.004), and major bleeding events (7.3% vs 11.8%, HR 0.60, 95% CI 0.43 to 0.86, p = 0.004) compared with unfractionated heparin plus glycoprotein IIb/IIIa inhibitor. Randomization to PES compared with bare-metal stenting resulted in a significant lower rate of target vessel revascularization (13.2% vs 19.8%, HR 0.64, 95% CI 0.47 to 0.86, p = 0.003) with no significant differences in stent thrombosis, reinfarction, or death. In conclusion, in patients with STEMI who underwent primary PCI of LAD, the use of bivalirudin was associated with a reduction in mortality and bleeding rates at 3 years. PES reduced revascularization rates in this population but did not have a significant impact on mortality.