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Background: Skeletal metastases from renal cell carcinoma are highly destructive vascular lesions. They pose unique surgical challenges due to the risk of life-threatening hemorrhage and resistance to other treatments. The goal of this retrospective study was to evaluate factors that may affect survival after surgical treatment of metastases of renal cell carcinoma.Methods: We performed a retrospective review of a series of 295 consecutive patients who had been treated for metastatic renal cell carcinoma at one institution between 1974 and 2004. There were 226 men and sixty-nine women. A total of 368 metastases of renal cell tumors to the extremities and pelvis were treated. The surgical procedures included curettage with cementing and/or internal fixation (214 tumors), en bloc resection (117), closed nailing (twenty-seven), amputation (four), and other measures (six). Overall survival was calculated with Kaplan-Meier analysis. The log-rank test was used to evaluate the effect of different variables on overall survival.Results: The overall patient survival rates at one and five years were 47% and 11%, respectively. The metastatic pattern had a significant effect on the survival rate (p < 0.0001): patients with a solitary bone metastasis had the most favorable overall survival rate. Patients with multiple bone-only metastases had a better survival rate than patients with pulmonary metastases (p = 0.009). A clear-cell histological subtype was also associated with better survival (p < 0.0001). The tumor grade did not predict survival (p = 0.17). Fifteen patients (5%) died within four weeks after surgery. The causes included acute pulmonary failure (seven patients), multiorgan failure (six), cerebrovascular accident (one), and hypercalcemia (one). There were no deaths attributable to intraoperative hemorrhage.Discussion: Survival beyond twelve months is possible for a substantial proportion of patients with metastatic renal cell carcinoma. Patients with a clear-cell histological subtype, bone-only metastases, and a solitary metastasis have superior survival rates. The presence of pulmonary metastases does not predict early death in a reliable manner, and some patients may survive for years with pulmonary and systemic disease. The data are important for surgeons to consider when choosing treatment for these patients. For example, local control of disease and implant stability are important issues for patients with a potential for a long duration of survival. [ABSTRACT FROM AUTHOR]

Intralesional excision of intraosseous grade 1 periacetabular chondrosarcoma may seem an attractive alternative to the current recommendation of joint-sacrificing, en bloc resection. We report eight patients who initially underwent this treatment to identify if local tumor control can be achieved consistently. All patients had a percutaneous biopsy that was interpreted as grade 1 chondrosarcoma. The final histology after curettage indicated Grade 1 chondrosarcoma in five patients, Grade 2 in two, and dedifferentiated chondrosarcoma in one. Three of the five patients with true grade 1 chondrosarcoma have been free of disease at a median followup of 108 months. The other two patients with grade 1 chondrosarcoma on the curettage specimen recurred as higher-grade tumors. Three patients died of high-grade chondrosarcoma at a median of 23 months (range 17-72 months). Overall, the majority of patients in this cohort had either a misdiagnosis or recurrence of higher-grade disease. Based on these observations, in the absence of a predictable method to identify the true intraosseous grade 1 chondrosarcomas of the pelvis, curettage must be undertaken with the understanding that a percutaneous biopsy may misrepresent the histologic grade and that curettage may result in a higher risk of recurrence.Level of Evidence: Level II, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

Background: Cyclo-oxygenase-2 (COX-2) selective inhibitors have been associated with an increased risk of thrombotic cardiovascular events in placebo-controlled trials, but no clinical trial has been reported with the primary aim of assessing relative cardiovascular risk of these drugs compared with traditional non-steroidal anti-inflammatory drugs (NSAIDs). The MEDAL programme was designed to provide a precise estimate of thrombotic cardiovascular events with the COX-2 selective inhibitor etoricoxib versus the traditional NSAID diclofenac.Methods: We designed a prespecified pooled analysis of data from three trials in which patients with osteoarthritis or rheumatoid arthritis were randomly assigned to etoricoxib (60 mg or 90 mg daily) or diclofenac (150 mg daily). The primary hypothesis stated that etoricoxib is not inferior to diclofenac, defined as an upper boundary of less than 1.30 for the 95% CI of the hazard ratio for thrombotic cardiovascular events in the per-protocol analysis. Intention-to-treat analyses were also done to assess consistency of results. These trials are registered at http://www.clinicaltrials.gov with the numbers NCT00092703, NCT00092742, and NCT00250445.Findings: 34 701 patients (24 913 with osteoarthritis and 9 787 with rheumatoid arthritis) were enrolled. Average treatment duration was 18 months (SD 11.8). 320 patients in the etoricoxib group and 323 in the diclofenac group had thrombotic cardiovascular events, yielding event rates of 1.24 and 1.30 per 100 patient-years and a hazard ratio of 0.95 (95% CI 0.81-1.11) for etoricoxib compared with diclofenac. Rates of upper gastrointestinal clinical events (perforation, bleeding, obstruction, ulcer) were lower with etoricoxib than with diclofenac (0.67 vs 0.97 per 100 patient-years; hazard ratio 0.69 [0.57-0.83]), but the rates of complicated upper gastrointestinal events were similar for etoricoxib (0.30) and diclofenac (0.32).Interpretation: Rates of thrombotic cardiovascular events in patients with arthritis on etoricoxib are similar to those in patients on diclofenac with long-term use of these drugs. [ABSTRACT FROM AUTHOR]

In the United States each year, >5.3 million patients present to emergency departments with chest discomfort and related symptoms. Ultimately, >1.4 million individuals are hospitalized for unstable angina and non-ST-segment elevation myocardial infarction. For emergency physicians and cardiologists alike, these patients represent an enormous challenge to accurately diagnose and appropriately treat. This update of the 2002 American College of Cardiology/American Heart Association Guidelines for the Management of Patients with Unstable Angina and Non-ST-Segment Elevation Myocardial Infarction (UA/NSTEMI) provides an evidence-based approach to the diagnosis and treatment of these patients in the emergency department, in-hospital, and after hospital discharge. Despite publication of the guidelines several years ago, many patients with UA/NSTEMI still do not receive guidelines-indicated therapy. [ABSTRACT FROM AUTHOR]

Cholesterol-lowering therapies have been shown in clinical trials to have a substantial impact on cardiovascular risk, incidence of cardiovascular events, and mortality. ATP III and its 2004 update recommend aggressive lipid-lowering strategies for several categories of at-risk patients; early and aggressive cholesterol-lowering therapy is beneficial both clinically and with regard to cost-effectiveness, as treatment of patients at risk can reduce the incidence of costly disease-related events. Patient screening to ensure proper treatment of those at highest risk is also important. While secondary prevention has been shown to reduce the costs associated with cardiovascular morbidities, primary prevention can also be cost-effective in some scenarios. Programs that aim to increase patient adherence to treatment can also provide a cost benefit, as therapies that are not used as pre-scribed are generally not cost-effective. Increased adherence, improved tolerability, and lower drug costs may all be provided by newer therapeutic options, such as single-tablet formulations of effective combination therapy regimens. [ABSTRACT FROM AUTHOR]

The results of recent clinical trials emphasize the importance of lowering LDL cholesterol levels with respect to cardiovascular risk. Most patients treated clinically for hypercholesterolemia are unsuccessful at reaching goals for LDL cholesterol put forth by US and European guidelines. The proposed new lower targets, based on clinical trials such as PROVE IT-TIMI 22, will lead to further challenges in patients' achievement of LDL cholesterol goals. Often, physicians, pharmacists, and patients are concerned about the safety of higher doses of statins, leading to inadequate statin dose titration. Patients may have more success at reaching their LDL cholesterol goals by using an effective medication regimen that decreases the need for statin titration. Several combination treatments, including fibrate/statin, niacin/statin, and ezetimibe/statin, are effective at reducing LDL cholesterol levels using lower doses of statin drugs. The dual inhibition of cholesterol absorption and cholesterol synthesis with ezetimibe/statin is a novel, unique strategy for achieving lower LDL targets. [ABSTRACT FROM AUTHOR]

Context: The American College of Cardiology/American Heart Association (ACC/AHA) guidelines for the management of non-ST-segment elevation acute coronary syndromes (NSTE ACS) recommend early invasive management for high-risk patients, given the benefits with this approach demonstrated in randomized clinical trials.Objectives: To determine the use and predictors of early invasive management strategies (cardiac catheterization <48 hours following presentation) in high-risk patients with NSTE ACS and to examine the association of early invasive management with mortality.Design, Setting, and Patients: The CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the ACC/AHA Guidelines) Quality Improvement Initiative evaluated care patterns and outcomes for 17,926 high-risk NSTE ACS patients (positive cardiac markers and/or ischemic electrocardiographic changes) based on ACC/AHA guidelines recommendations at 248 US hospitals with catheterization and revascularization facilities between March 2000 and September 2002.Main Outcome Measures: Use of early invasive management within 48 hours of presentation, predictors of early invasive management, and in-hospital mortality. Results Of the 17,926 patients analyzed, 8037 (44.8%) underwent early cardiac catheterization less than 48 hours following presentation. Predictors of early invasive management included cardiology care, younger age, lack of prior or current congestive heart failure, lack of renal insufficiency, ischemic electrocardiographic changes, positive cardiac markers, white race, and male sex. Patients treated with early invasive management were more likely to be treated with medications and interventions recommended by the ACC/AHA guidelines and had a lower risk of in-hospital mortality after adjusting for differences in clinical characteristics and after comparing propensity-matched pairs (2.5% vs 3.7%, P<.001). Conclusions An early invasive management strategy is not utilized in the majority of high-risk patients with NSTE ACS. This strategy appears to be reserved for patients without significant comorbidities and those cared for by cardiologists and is associated with a lower risk of in-hospital mortality. [ABSTRACT FROM AUTHOR]

Objectives: We hypothesized that elevated B-type natriuretic peptide (BNP) levels would be associated with a greater severity of angiographic disease and a greater extent of myocardium at risk. Background: Elevations of BNP have been associated with increased risk of adverse outcomes in patients with unstable angina and non-ST-segment elevation myocardial infarction (UA/NSTEMI). Methods: Of the 2,220 patients with UA/NSTEMI enrolled in the Treat Angina with Aggrastat and Determine Cost of Therapy with an Invasive or Conservative Strategy-Thrombolysis In Myocardial Infarction-18 (TACTICS-TIMI-18) trial, 276 randomized to the invasive arm had both baseline BNP levels and angiographic core laboratory data. Patients were categorized according to their baseline BNP levels as < or =80 or >80 pg/ml. Results: A total of 233 patients (84%) had BNP levels >80 pg/ml, and 43 (16%) had admission BNP levels >80 pg/ml. Patients with BNP >80 pg/ml had tighter culprit vessel stenosis on quantitative coronary angiography (median stenosis 76% vs. 67%, p = 0.004) and a higher (slower) corrected TIMI frame count (median CTFC 43 vs. 30, p = 0.018) in the culprit vessel. The median BNP level was higher in patients with a left anterior descending coronary artery (LAD) versus non-LAD culprit lesion location (median BNP level 40 vs. 24 pg/ml, p = 0.005), and the culprit artery was more often the LAD in patients with BNP >80 pg/ml compared with < or =80 pg/ml (44% vs. 30%, p = 0.06). Conclusions: Among patients with UA/NSTEMI, elevated BNP levels are associated with tighter culprit stenosis, higher CTFC, and LAD involvement. These findings suggest that elevated BNP may be associated with a greater severity and extent of myocardial ischemic territory during the index event and may partly explain the association between elevated BNP and adverse outcomes. [ABSTRACT FROM AUTHOR]

Context: In the Treat Angina with Aggrastat and Determine Cost of Therapy with an Invasive or Conservative Strategy (TACTICS)-Thrombolysis in Myocardial Infarction (TIMI) 18 trial, patients with either unstable angina or non-ST-segment elevation myocardial infarction (UA/NSTEMI) treated with the platelet glycoprotein (Gp IIb/IIIa) inhibitor tirofiban had a significantly reduced rate of major cardiac events at 6 months with an early invasive vs a conservative strategy.Objective: To examine total 6-month costs and long-term cost-effectiveness of an invasive vs a conservative strategy.Design: Randomized controlled trial including a priori economic end points.Setting: Hospitalization for UA/NSTEMI with 6-month follow-up period.Patients: A total of 2220 patients with UA/NSTEMI; economic data from 1722 patients at US-non-VA hospitals.Intervention: Early invasive strategy with routine catheterization and revascularization as appropriate vs a conservative strategy with catheterization performed only for recurrent ischemia or a positive stress test.Main Outcome Measure: Total 6-month costs and incremental cost-effectiveness ratio.Results: The average initial hospitalization costs among those in the invasive strategy group were $15714 vs $14047 among those in the conservative strategy group, a difference of $1667 (95% confidence interval [CI], $387-3091). The in-hospital costs were offset significantly at the 6-month follow-up, with an average cost in the invasive group of $6098 vs $7180 in the conservative group, a difference of $1082 (95% CI, -$2051 to $76). The average total costs at 6 months, including productivity costs, for the invasive group was $21 813 vs $21 227 for the conservative group, a $586 difference (95% CI, -$1087 to $2486). The average 6-month costs excluding productivity costs in the invasive group was $19 780 vs $19 111 in the conservative group, a difference of $670, 95% CI; (-$1035 to $2321). Estimated cost per year of life gained for the invasive strategy, based on projected life expectancy, was $12739 for the base case, and ranged from $8371 to $25769, based on model assumptions.Conclusions: In patients with UA/NSTEMI treated with the Gp IIb/IIIa inhibitor tirofiban, the clinical benefit of an early invasive strategy was achieved with a small increase in cost, yielding favorable projected estimates of cost per year of life gained. These results support the broader use of an early invasive strategy in these patients. [ABSTRACT FROM AUTHOR]

The management of acute coronary syndromes has changed: treatment goals have been expanded, early catheterization is recommended for more patients, and new drugs are pivotal. [ABSTRACT FROM AUTHOR]

Context: Cardiac troponins I (cTnI) and T (cTnT) are useful for assessing prognosis in patients with unstable angina and non-ST-segment elevation myocardial infarction (UA/NSTEMI). However, the use of cardiac troponins for predicting benefit of an invasive vs conservative strategy in this patient population is not clear.Objective: To prospectively test whether an early invasive strategy provides greater benefit than a conservative strategy in acute coronary syndrome patients with elevated baseline troponin levels.Design: Prospective, randomized trial conducted from December 1997 to June 2000.Setting: One hundred sixty-nine community and tertiary care hospitals in 9 countries.Participants: A total of 2220 patients with acute coronary syndrome were enrolled. Baseline troponin level data were available for analysis in 1821, and 1780 completed the 6-month follow-up.Interventions: Patients were randomly assigned to receive (1) an early invasive strategy of coronary angiography between 4 and 48 hours after randomization and revascularization when feasible based on coronary anatomy (n = 1114) or (2) a conservative strategy of medical treatment and, if stable, predischarge exercise tolerance testing (n = 1106). Conservative strategy patients underwent coronary angiography and revascularization only if they manifested recurrent ischemia at rest or on provocative testing.Main Outcome Measure: Composite end point of death, MI, or rehospitalization for acute coronary syndrome at 6 months.Results: Patients with a cTnI level of 0.1 ng/mL or more (n = 1087) experienced a significant reduction in the primary end point with the invasive vs conservative strategy (15.3% vs 25.0%; odds ratio [OR], 0.54; 95% confidence interval [CI], 0.40-0.73). Patients with cTnI levels of less than 0.1 ng/mL had no detectable benefit from early invasive management (16.0% vs 12.4%; OR, 1.4; 95% CI, 0.89-2.05; P<.001 for interaction). The benefit of invasive vs conservative management through 30 days was evident even among patients with low-level (0.1-0.4 ng/mL) cTnI elevation (4.4% vs 16.5%; OR, 0.24; 95% CI, 0.08-0.69). Directionally similar results were observed with cTnT.Conclusion: In patients with clinically documented acute coronary syndrome who are treated with glycoprotein IIb/IIIa inhibitors, even small elevations in cTnI and cTnT identify high-risk patients who derive a large clinical benefit from an early invasive strategy. [ABSTRACT FROM AUTHOR]

Background: Use of resources for patients with acute chest pain may be improved with clinical strategies that integrate research, Bayesian analysis, and expert opinion.Objectives: To 1) develop a critical pathway for management of patients with acute chest pain who are at low risk for complications of ischemic heart disease and 2) assess the potential effects of implementation of the pathway on patient safety and resource use.Design: Evidence-based consensus and prospective cohort study.Setting: Urban teaching hospital.Patients: Patients at least 30 years of age who were seen in the emergency department for chest pain and who did not have a history of trauma or abnormalities on radiologic study.Intervention: Physician-opinion leaders defined criteria for patient inclusion in the pathway and for remaining on the pathway after 6 or 12 hours of observation. Criteria were defined for appropriateness of direct admission, direct discharge, or 6 hours of observation followed by exercise treadmill testing.Measurements: Number of patients admitted to the hospital, number of days that patients were hospitalized, and clinical outcome.Results: 2898 of 4585 patients (63%) were admitted to the hospital; of the 2898, 1152 (40%) were classified as potentially eligible for the pathway and 1068 (93%) had a benign clinical course during the initial observation period. The 1068 patients had a mean length of stay of 2.8 +/- 4.8 days. If 47% of these patients had been discharged after observation and exercise testing, implementation of the pathway would have reduced the number of admissions by 505 (17%) and days of hospitalization by 1407 (11%).Conclusions: Retrospective analysis suggests that a critical pathway for patients with acute chest pain may substantially reduce resource use. Prospective study is needed to ensure increased efficiency without increased adverse outcomes. [ABSTRACT FROM AUTHOR]

Major advances in the diagnosis of acute coronary syndromes (ACS) have occurred in 2011, but physicians treating ACS still walk the tightrope between efficacy and bleeding. Key publications have shed light on this delicate balance and heralded a new era of novel oral anticoagulants for the treatment of ACS. [ABSTRACT FROM AUTHOR]