Traditional Risk Parameters Research Articles

Evaluation of treatment effects in patients with endometrial cancer and POLE mutations: An individual patient data meta-analysis.

Endometrial cancers (ECs) with somatic mutations in DNA polymerase epsilon (POLE) are characterized by unfavorable pathological features, which prompt adjuvant treatment. Paradoxically, women with POLE-mutated EC have outstanding clinical outcomes, and this raises concerns of overtreatment. The authors investigated whether favorable outcomes were independent of treatment. A PubMed search for POLE and endometrial was restricted to articles published between March 1, 2012, and March 1, 2018, that provided individual patient data (IPD), adjuvant treatment, and survival. Following the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) reporting guidelines for IPD, the authors used univariate and multivariate one-stage meta-analyses with mixed effects Cox models (random effects for study cohorts) to infer the associations of treatment, traditional prognostic factors, and outcome, which was defined as the time from first diagnosis to any adverse event (progression/recurrence or death from EC). Three hundred fifty-nine women with POLE-mutated EC were identified; 294 (82%) had pathogenic mutations. Worse outcomes were demonstrated in patients with nonpathogenic POLE mutations (hazard ratio, 3.42; 95% confidence interval, 1.47-7.58; log-rank P < .01). Except for stage (P < .01), traditional prognosticators were not associated with progression/recurrence or death from disease. Adverse events were rare (11 progressions/recurrences and 3 disease-specific deaths). Salvage rates in patients who experienced recurrence were high and sustained, with 8 of 11 alive without evidence of disease (range, 5.5-14.2 years). Adjuvant treatment was not associated with outcome. Clinical outcomes for ECs with pathogenic POLE mutations are not associated with most traditional risk parameters, and patients do not appear to benefit from adjuvant therapy. The observed low rates of recurrence/progression and the high and sustained salvage rates raise the possibility of safely de-escalating treatment for these patients. Ten percent of all endometrial cancers have mutations in the DNA repair gene DNA polymerase epsilon (POLE). Women who have endometrial cancers with true POLE mutations experience almost no recurrences or deaths from their cancer even when their tumors appear to have very unfavorable characteristics. Additional therapy (radiation and chemotherapy) does not appear to improve outcomes for women with POLE-mutated endometrial cancer, and this supports the move to less therapy and less associated toxicity. Diligent classification of endometrial cancers by molecular features provides valuable information to inform prognosis and to direct treatment/no treatment.

The Low Downside Risk Effect - Lower Risk and Higher Returns with Low Downside Risk

Past downside risk is shown to have an even stronger influence on future stock sector performance than past low risk as represented by traditional risk parameters that represent both down- and upside risk in one single measure.The fact past low (downside) risk stocks outperform past high risk stocks in the future (or the fact past high risk stocks don’t outperform past low risk stocks), is usually seen as an anomaly to be explained by many sources of biased investor preferences for high risk stocks. As is pointed out in this paper, the outperformance of low over high risk stocks isn't an anomaly and can not be explained by biased investor preferences for risky stocks. Instead, I suggest an opposite view: in line with basic micro economics, financial economics and behavioral finance principles the market values highest and trades accordingly what it likes most: low risk. And even more so: low downside risk. Vice versa, I suggest the market values lowest and trades accordingly what it dislikes most: high risk and particularly high downside risk.

Prognostic Value of Contrast-enhanced Cardiac Magnetic Resonance Imaging in Patients with Newly Diagnosed Non-Ischemic Cardiomyopathy: Cohort Study

BackgroundOwing to its variable course from asymptomatic cases to sudden death risk stratification is of paramount importance in newly diagnosed non-ischemic cardiomyopathy. We tested whether late gadolinium enhancement (LGE) assessed by cardiac magnetic resonance (CMR) imaging is a prognostic marker in consecutive patients with newly diagnosed non-ischemic cardiomyopathy.MethodsWe enrolled 185 patients who presented for evaluation of newly diagnosed non-ischemic cardiomyopathy. Coronary artery disease was excluded by coronary angiography. Following risk markers were additionally assessed: NYHA functional class (≥II), brain natriuretic peptide (>100 ng/l), troponin I (TnI, ≥0.03 µg/l), left ventricular ejection fraction (LVEF, ≤40%), left ventricular enddiastolic diameter (>55 mm) and QRS duration (>98 ms). Endpoint of the study was the composite of all-cause mortality, heart transplantation, aborted sudden death, sustained ventricular tachycardia or hospitalization due to decompensated heart failure within three years of follow-up.ResultsDuring median follow-up of 21 months, 54 patients (29.2%) reached the composite endpoint. Ninety-four of the 185 patients (50.8%) were judged LGE-positive. Prognosis of LGE-positive patients was significantly worse than that of LGE-negative patients (cumulative 3-year event rates of 67.4% in LGE-positive and 27.2% in LGE-negative patients, respectively; p = 0.021). However, in multivariable analysis, presence of LGE was not an independent predictor of outcome. Only LVEF ≤40% and TnI ≥0.03 µg/l were independent risk predictors of the composite endpoint yielding relative risks of 3.9 (95% CI 1.9–8.1; p<0.0001) and 2.2 (95% CI 1.2–4.0; p = 0.014), respectively.ConclusionsIn consecutive patients presenting with newly diagnosed non-ischemic cardiomyopathy, LGE-positive patients had worse prognosis. However, only traditional risk parameters like left ventricular performance and cardiac biomarkers but not presence of LGE were independent risk predictors.

Cardiovascular risk in patients with rheumatoid arthritis: assessment of several traditional risk parameters and a German risk score model

The present cross-sectional data demonstrate cardiovascular (CV) risk in patients with rheumatoid arthritis (RA). The cross-sectional data were part of an interventional trial that included 100 patients with defined RA. Traditional CV risk parameters and risk score calculation for the German population were used to assess the CV risk profile in the collective given. Proatherogenic lipid profile characterised by increased total cholesterol (≥ 5.2 mmol/l) and LDL cholesterol (≥ 3.5 mmol/l) levels was measured in 85 and 66%, respectively, of the study population. Elevated concentrations of homocysteine (≥ 10 μmol/l) were reached by 67%. The prevalence of patients at high CV risk was 12% and increased up to 42% after using a multiplication factor of 1.5. No association was seen between the CV risk SCORE and DAS 28 or disease duration. RA patients in this study showed a proatherogenic risk profile with regard to the CV risk factors evaluated. The calculation of a 10-year risk using German risk charts might have led to an overall underestimation of the mean CV risk. Cardiovascular co-morbidity in RA patients must be seen as a major prevention and treatment target and should be monitored adequately.

Dissociation of Blood Pressure and Resistance Artery Structure: Potential Clinical Implications

Essential hypertension (EH) is associated with structural changes in small arteries (SMASCH) in terms of wall thickening and lumen narrowing throughout the entire resistance circulation. This remodelling process occurs early in EH development and is an important contributor to the elevation of vascular resistance. SMASCH also decreases the vasodilatory capability leading to demand-related organ dysfunction (e.g. microvascular angina) and later contributes to organ failure as seen in hypertensive heart and renal failure. In large groups of patients, office blood pressure (BP) precisely predicts strokes and myocardial infarctions, but it is difficult to apply risk prediction equations based on studies of large numbers of patients in individual patients. Office BP may be a rather poor predictor of future cardiovascular events. Adding other risk factors unrelated to BP (SCORE factors) improves risk prediction, and in subgroups with intermediate risk, there may be added value of considering BP-related parameters such as albuminuria or left ventricular hypertrophy. Being directly related to the process of hyper-resistance and dissociated from BP itself, measurements of SMASCH may contribute to risk over and above office BP and other traditional risk parameters. Furthermore, as only antihypertensive treatment regimens resulting in vasodilatation seem to improve SMASCH, this parameter has the potential to guide and improve the management of EH. SMASCH can be assessed, for example, by plethysmography in the forearm or by echocardiography in the heart. These techniques are accurate and reproducible and could constitute part of the diagnostic apparatus for EH patients. This review focuses on methodological issues of SMASCH, haemodynamic consequences, implementation in the clinical setting and suggestions for future research.