Summary Background The likelihood of tumour recurrence after nephrectomy in localised clear cell renal cell carcinoma is well characterised by clinical and pathological parameters. However, these ...assessments can be improved and personalised by the addition of molecular characteristics of each patient's tumour. We aimed to develop and validate a prognostic multigene signature to improve prediction of recurrence risk in clear cell renal cell carcinoma. Methods In the development stage, we investigated the association between expression of 732 genes, measured by reverse-transcription PCR, and clinical outcome in 942 patients with stage I–III clear cell renal cell carcinoma who had undergone a nephrectomy at the Cleveland Clinic (OH, USA). 516 genes were associated with recurrence-free interval. 11 of these genes were selected by further statistical analyses, and were combined with five reference genes (ie, 16 genes in total), from which a recurrence score algorithm was developed. The recurrence score was then validated in an independent cohort of 626 patients from France with stage I–III clear cell renal cell carcinoma who had also undergone nephrectomy. The association between the recurrence score and the risk of recurrence and cancer-specific survival in the first 5 years after surgery was assessed using Cox proportional hazard regression, stratified by tumour stage (stage I vs stage II vs III). Findings In our primary univariate analysis, the continuous recurrence score (median 37, IQR 31–45) was significantly associated with recurrence-free interval (hazard ratio 3·91 95% CI 2·63–5·79 for a 25-unit increase in score, p<0·0001). In multivariable analyses, the recurrence score was significantly associated with the risk of tumour recurrence (hazard ratio per 25-unit increase in the score 3·37 95% CI 2·23–5·08, p<0·0001) after stratification by stage and adjustment for tumour size, grade, or Leibovich score. The recurrence score was able to identify a clinically significant number of both high-risk stage I and low-risk stage II–III patients. A heterogeneity study on separate samples showed little to no intratumoural variability among the 16 genes. Interpretation Our findings validate the recurrence score as a predictor of clinical outcome in patients with stage I–III clear cell renal cell carcinoma, providing a more accurate and individualised risk assessment beyond existing clinical and pathological parameters. Funding Genomic Health Inc and Pfizer Inc.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Background The purpose of this study was to assess temporal trends in clinical characteristics, treatments, quality indicators, and outcomes for heart failure (HF) hospitalizations. Methods ...Characteristics, treatments, quality measures, and inhospital outcomes were measured over 12 consecutive quarters (January 2002 to December 2004) using data from 159 168 enrollments from 285 ADHERE hospitals. Results Baseline characteristics were similar or showed only modest changes, and severity of illness by logistic regression was unchanged over all 12 quarters. Inhospital treatment changed significantly over time with inotrope use decreasing from 14.7% to 7.9% ( P < .0001). Discharge instructions increased 133%; smoking counseling, 132%; left ventricular function measurement, 8%; and β-blocker use, 29% (all P < .0001). Clinical outcomes improved over time, including need for mechanical ventilation, which decreased 5.3% to 3.4% (relative risk 0.64, P < .0001); length of stay (mean), 6.3 to 5.5 days; and mortality, 4.5% to 3.2% (relative risk 0.71, P < .0001). Conclusions Over a 3-year period, demographics and clinical characteristics were relatively similar, but significant changes in intravenous therapy, enhancements in conformity to quality-of-care measures, increased administration of evidence-based HF medications, and substantial improvements in inhospital morbidity and mortality were observed during hospitalization for HF.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Admission B-Type Natriuretic Peptide Levels and In-Hospital Mortality in Acute Decompensated Heart Failure Gregg C. Fonarow, William F. Peacock, Christopher O. Phillips, Michael M. Givertz, Margarita ...Lopatin, for the ADHERE Scientific Advisory Committee and Investigators The relationship between B-type natriuretic peptide (BNP) and mortality during acute heart failure hospitalizations was assessed using ADHERE (Acute Decompensated Heart Failure National Registry). The BNP quartiles in 48,629 hospitalizations were quartile (Q) Q1 (<430), Q2 (430 to 839), Q3 (840 to 1,729), and Q4 (≥1,730 pg/ml). There was a near-linear relationship between BNP quartiles and mortality: Q1 (1.9%), Q2 (2.8%), Q3 (3.8%), Q4 (6.0%), p < 0.0001. The BNP quartile remained predictive of mortality even after adjustment for age, gender, systolic blood pressure, blood urea nitrogen, creatinine, sodium, pulse, and dyspnea at rest, Q4 versus Q1 (adjusted odds ratio 2.23 range 1.91 to 2.62, p < 0.0001). The BNP quartiles independently predicted in-hospital mortality in patients with reduced and preserved systolic function.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background Prior studies on chronic systolic heart failure (HF) have demonstrated that body mass index (BMI) is inversely associated with mortality, the so-called obesity paradox. The aim of this ...study was to determine whether BMI influences the mortality risk in acute decompensated HF, a subject not previously studied. Methods The Acute Decompensated Heart Failure National Registry was analyzed for acute HF hospitalizations in 263 hospitals in the United States from October 2001 through December 2004. Patients with documented height and weight were divided into BMI (measured in kilograms per square meter) quartiles. Inhospital mortality by BMI quartile for all the patients and for those with reduced (n = 43 255) and preserved (n = 37 901) systolic function was assessed. Results Body mass index quartiles in the 108 927 hospitalizations were QI (16.0-23.6 kg/m2 ), QII (23.7-27.7 kg/m2 ), QIII (27.8-33.3 kg/m2 ), and QIV (33.4-60.0 kg/m2 ). Patients in the higher BMI quartiles were younger, had more diabetes, and had a higher left ventricular ejection fraction. Inhospital mortality rates decreased in a near-linear fashion across successively higher BMI quartiles. After adjustments for age, sex, blood urea nitrogen, blood pressure, creatinine, sodium, heart rate, and dyspnea at rest, BMI quartile still predicted mortality risk. For every 5-U increase in BMI, the odds of risk-adjusted mortality was 10% lower (95% CI 0.88-0.93, P < .0001). Conclusions In this cohort of hospitalized patients with HF, higher BMI was associated with lower inhospital mortality risk. The relationship between BMI and adverse outcomes in HF appears to be complex and deserving of further study.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
B-type natriuretic peptide (BNP) and cardiac troponin (Tn) I or T have been demonstrated to provide prognostic information in patients with acute coronary syndromes. Whether admission BNP and Tn ...levels provide additive prognostic value in acutely decompensated heart failure (HF) has not been well studied. Hospitalizations for HF from April 2003 to December 2004 entered into ADHERE were analyzed. BNP assessment on admission was performed in 48,629 (63%) of 77,467 hospitalization episodes. Tn assessment was performed in 42,636 (88%) of these episodes. In-hospital mortality was assessed using logistic regression models adjusted for age, gender, blood urea nitrogen, systolic blood pressure, creatinine, sodium, pulse, and dyspnea at rest. Median BNP was 840 pg/ml (interquartile range 430 to 1,730). Tn was increased in 2,370 (5.6%) of 42,636 HF episodes. BNP above the median and increased Tn were associated with significantly increased risk of in-hospital mortality (odds ratios OR 2.09 and 2.41 respectively, each p value <0.0001). Mortality was 10.2% in patients with BNP ≥840/Tn increased compared with 2.2% with BNP <840/Tn not increased (OR 5.10, p <0.0001). After covariate adjustment, mortality risk remained significantly increased with BNP ≥840/Tn not increased (adjusted OR 1.56, 95% confidence interval 1.40 to 1.79, p <0.0001), BNP <840/Tn increased (adjusted OR 1.69, 95% confidence interval 1.17 to 2.45, p = 0.006), and BNP ≥840/Tn increased (adjusted OR 3.00, 95% confidence interval 2.47 to 3.66, p <0.0001). Admission BNP and cardiac Tn levels are significant, independent predictors of in-hospital mortality in acutely decompensated HF. Patients with BNP levels ≥840 pg/ml and increased Tn levels are at particularly high risk for mortality. In conclusion, a multimarker strategy for the assessment of patients hospitalized with HF adds incremental prognostic information.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Heart failure (HF) with normal ejection fraction (EF) is an increasingly common presentation of acute decompensated HF. Differences between patients with HF and truly normal EF and those with mildly ...impaired EF have not been described. The Acute Decompensated Heart Failure Registry (ADHERE) contains information on >100,000 HF hospitalizations and may provide insight into this distinction. The ADHERE database was used to investigate differences between patients hospitalized with HF and severely (<25%), moderately (25% to 40%), and mildly (40% to 55%) decreased EF and those with normal EF (≥55%). The group with normal EF was 69% women with a mean age of 74 years (p <0.0001 vs all other groups). Coronary artery disease was less frequent in the normal EF group, and hypertension played a larger role. Patients with EF ≥55% had increased pulse pressure, suggesting a role for arterial stiffening. Treatment differed by EF. Creatinine increased ≥0.5 mg/dl more often in the group with HF and normal EF than in the group with HF and severely decreased EF. In-hospital mortality and length of stay in the intensive care unit varied inversely with EF; overall length of stay was similar. In conclusion, patients with HF and normal EF are more likely to be women, have a history of high pulse pressure hypertension, less coronary artery disease, and a lower risk of inpatient death but a higher likelihood of deterioration in renal function during hospitalization. These observations may be important considerations in the design of future clinical trials.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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