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Osteoprotegerin is a significant prognostic factor for overall survival in patients with primary systemic amyloidosis independent of the Mayo staging.

ABSTRACT: Bone metabolism has not been systematically studied in primary (AL) amyloidosis. Thus we prospectively evaluated bone remodeling indices in 102 patients with newly diagnosed AL amyloidosis, 35 healthy controls, 35 newly diagnosed myeloma and 40 monoclonal gammopathy of undetermined significance patients. Bone resorption markers (C-telopeptide of type-1 collagen, N-telopeptide of type-1 collagen) and osteoclast regulators (soluble receptor activator of nuclear factor-κB ligand (sRANKL), osteoprotegerin (OPG)) were increased in AL patients compared with controls (P<0.01), but bone formation was unaffected. Myeloma patients had increased bone resorption and decreased bone formation compared with AL patients, while sRANKL/OPG ratio was markedly decreased in AL, due to elevated OPG in AL (P<0.001). OPG correlated with N-terminal pro-brain natriuretic peptide (P<0.001) and was higher in patients with cardiac involvement (P=0.028) and advanced Mayo stage (P=0.001). OPG levels above the upper value of healthy controls was associated with shorter survival (34 versus 91 months; P=0.026), while AL patients with OPG levels in the top quartile had very short survival (12 versus 58 months; P=0.024). In Mayo stage 1 disease, OPG identified patients with poor survival (12 versus >60 months; P=0.012). We conclude that increased OPG in AL is not only a compensation to osteoclast activation but may also reflect early cardiac damage and may identify patients at increased risk of death within those with earlier Mayo stage.

SUBMITTER: Kastritis E

PROVIDER: S-EPMC4648482 | biostudies-other | 2015

REPOSITORIES: biostudies-other

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Project description:Purpose This study was launched to ascertain the independent prognostic factors influencing the overall survival (OS) prognosis of intracranial subependymoma and construct a prognostic model to predict OS time. Materials and methods We collected data from patients with intracranial subependymoma, including treatment data, follow-up data, and clinical and pathological characteristics from the SEER database within 2004 to 2016, and patients were randomly classified into training and validation cohorts. Univariate and multivariate analyses were applied to the training group through building a Cox proportional hazards model. According to the results of multivariate analysis, we established a nomogram to forecast the OS rate of the per-case patient graphically, then calculated the accuracy of verification in both training and validation cohorts by concordance index (C-index). Univariate and multivariate analyses were used for different subgroups of unoperated versus operated, gross total resection (GTR), subtotal resection (STR), and biopsy after using the propensity score matching (PSM) analyses. Results A total of 667 patients were enrolled, and we randomly assigned 535 patients (80.21%) into the training cohort and 132 patients (19.79%) into the validation cohort. Age [hazard ratio (HR) = 6.355; 95% confidence interval (CI), 2.240–18.029; p = 0.001] and sex (HR = 0.475; 95% CI, 0.232–0.974; p = 0.042) were the independent prognostic factors in the training cohort. On the basis of age and sex, the nomogram was established to predict the OS for every patient (C-index = 0.733 ± 0.065 in the training cohort and 0.850 ± 0.065 in the validation cohort), and calibration plots reflected the reliability of the nomogram. Age, gender, or laterality was the independent prognostic factor for OS in the different matched subgroups of unoperated versus operated, GTR, STR, and biopsy. Surgical treatment, race, year of diagnosis, insurance, tumor location, tumor size, pathology, tumor grade, and radiation were not statistically significantly different in OS for subependymoma in our research. Conclusion Age and sex were the independent prognostic variables for OS in intracranial subependymoma. According to our research, we should not be more inclined to choose conservative or surgical treatment. Nonetheless, the information that we present might be useful to suggest potential hypotheses to be tested in the clinical research setting.

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Osteoprotegerin is a significant prognostic factor for overall survival in patients with primary systemic amyloidosis independent of the Mayo staging.

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