Immunoparesis (hypogammaglobulinemia) is associated to an unfavorable prognosis in newly diagnosed Multiple myeloma (MM) patients. However, this finding has not been validated in an unselected ...population-based cohort. We analyzed 2558 newly diagnosed MM patients in the Danish Multiple Myeloma Registry representing the entire MM population in Denmark from 2005-2013. Two-thousand two hundred and fifty three patients (90%) presented with reduction below lower normal levels of at least one uninvolved immunoglobulin. Using multivariable Cox regression we found that high age, high ISS score, high LDH and IgA MM were associated to both shorter overall survival and progression free survival. Furthermore, bone marrow plasma cell % was associated to short progression free survival. Immunoparesis had no independent significant effect on OS (HR 0.9 (95%CI: 0.7;1.0; p = 0.12)). Likewise, the number of suppressed immunoglobulins or the relative degree of suppressed uninvolved immunoglobulins from lower normal level (quantitative immunoparesis) was not associated to OS in the multivariable analysis. However, quantitative immunoparesis with at least 25% reduction (from lower normal level) of uninvolved immunoglobulins was associated to shorter PFS for the entire population. The impact of quantitative immunoparesis on PFS was present irrespective of calendar periods 2005-2008 and 2009-2013. Our population-based study does not confirm that immunoparesis at diagnosis is an independent prognostic factor regarding OS. However, quantitative immunoparesis is associated to a shorter PFS.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Several risk scores for disease progression in patients with smoldering multiple myeloma (SMM) have been proposed; however, all have been developed using single‐center registries. To examine risk ...factors for time to progression (TTP) to multiple myeloma (MM) for SMM, we analyzed a nationwide population‐based cohort of 321 patients with newly diagnosed SMM registered within the Danish Multiple Myeloma Registry between 2005 and 2014. Significant univariable risk factors for TTP were selected for multivariable Cox regression analyses. We found that both an M‐protein ≥30 g/L and immunoparesis significantly influenced TTP (HR 2.7, 95%CI (1.5;4.7), P = 0.001, and HR 3.3, 95%CI (1.4;7.8), P = 0.002, respectively). High free light chain (FLC) ratio did not significantly influence TTP in our cohort. Therefore, our data do not support recent IMWG proposal of identifying patients with FLC ratio above 100 as having ultra high‐risk of transformation to MM. Using only immunoparesis and M‐protein ≥30 g/L, we created a scoring system to identify low‐, intermediate‐, and high‐risk SMM. This first population‐based study of patients with SMM confirms that an M‐protein ≥30 g/L and immunoparesis remain important risk factors for progression to MM.
Full text
Available for:
BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Background Overweight adults have low circulating concentrations of ANP (atrial natriuretic peptide) and proANP fragments. We tested the hypothesis that an intensive lifestyle intervention with an ...intended weight loss would increase plasma concentrations of a proANP fragment in overweight children. Methods and Results We measured MR‐proANP (midregional proANP) concentrations in plasma from overweight children who participated in the OOIS (Odense Overweight Intervention Study). OOIS randomized 115 overweight children (11–13 years, 55% girls) to an intensive day‐camp intervention arm with increased physical activity and healthy diet or to a less intensive standard intervention arm for 6 weeks. We used linear mixed‐effects modeling for repeated measures to estimate the difference in the mean change with 95% CIs in fasting plasma MR‐proANP concentrations between the 2 arms, and we used partial least squares regression analysis to identify candidate mediators. Differences in weight, fitness, and metabolic factors were also analyzed. At baseline, fasting plasma MR‐proANP concentrations were (median interquartile range) 35.0 pmol/L (26.8–42.0) in the day‐camp intervention arm and 37.2 pmol/L (31.7–44.7) in standard intervention arm participants, respectively. After 6 weeks intervention, children in the day‐camp intervention arm had increased their MR‐proANP (5.4 pmol/L 0.8–10.0, P =0.022) and their fitness (2.33 mL O 2 /min per kg 0.52–4.14, P =0.012) and they had deceased their body mass index (−2.12 kg/m 2 −2.59 to −1.65, P <0.001) as compared with children in standard intervention arm. In the partial least squares analysis, decreases in fasting insulin and in estimated insulin resistance were associated with the observed increase in MR‐proANP concentrations. Conclusions An intensive lifestyle intervention increases plasma MR‐proANP among overweight children. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01574352.
Summary
We compared the outcomes of multiple myeloma (MM) patients aged 21–40 and 41–60 years in the novel agent era. This case‐control study included 1089 patients between 2000 and 2015. Cases and ...controls were matched for sex, International Staging System (ISS) stage and institution. There were 173 patients in the younger group and 916 patients in the older group. Younger patients presented with a higher incidence of lytic lesions (82% vs. 72%; P = 0·04) and high‐risk cytogenetic abnormalities (83% vs. 68%; P = 0·007), but lower rate of elevated lactate dehydrogenase (21% vs. 44%; P < 0·001). Five‐ and 10‐year overall survival (OS) in younger versus older patients was 83% vs. 67% and 56% vs. 39%, respectively (P < 0·001). Similar results were seen when studying the subset of 780 patients who underwent autologous transplantation. Younger patients with ISS stage 1 had a better OS than older patients (P < 0·001). There was no survival difference between younger and older patients with ISS stage 2 or 3. Younger MM patients, aged 21–40 years, treated in the era of novel agents have a better OS than their counterparts aged 41–60 years, but the survival advantage observed in younger patients was lost in more advanced stages of MM.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Modulation of xenobiotic metabolism, including cytochrome P-450 (CYP) enzyme activities, due to dietary intakes of cruciferous vegetables, has been described in animals and humans, and the induction ...of CYP1A enzymes is suggested mainly to be related to the content of indolyl glucosinolates in these vegetables. The aim of the present study was to evaluate the effects on specific CYP activities of various broccoli samples containing different levels of glucosinolates. Groups of rats were fed 1 of 8 broccoli samples from 2 cultivars grown at different conditions. Thirteen different glucosinolates were quantified. The content of the 4 major glucosinolates, glucoraphanin (GRAP), glucoiberin, glucobrassicin (GB), and neoglucobrassicin (NeoGB) varied 5.6-, 2.7-, 3.2-, and 6.6-fold, respectively, among the broccoli samples. Dietary broccoli induced the CYP1A enzyme activities, 7-ethoxyresorufin-O-deethylase (EROD) and 7-methoxyresorufin-O-demethylase (MROD), in rat liver, weakly in colon, but not in kidney. In concordance, the hepatic metabolism of 2-amino-1-methyl-6-phenylimidazo(4,5-
b)pyridine (PhIP) to the proximate carcinogen N-OH-PhIP, a CYP1A-related activity, was enhanced by broccoli. The 7-pentoxyresorufin-O-depenthylase (PROD) activity, an assay for CYP2B1/2, was weakly induced in colon and kidney but not in liver by broccoli. The 2beta -OH- and 6beta -OH-testosterone hydroxylase activities were induced in liver microsomes, showing that broccoli increased CYP3A activity. The observed modulations of CYP activities depended clearly on the broccoli sample used, and significantly different responses were observed for different cultivars and growth conditions. These results indicate that modulation of CYP metabolism by broccoli may vary significantly in humans as well, as the content of glucosinolates and other active substances also varies between commercially available broccoli samples. The different effects depending on the vegetable sample eaten have to be considered in future experiments and dietary recommendations.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
In this paper, we develop adaptive linear prediction filters in the framework of maximum a posteriori (MAP) estimation. It is shown how priors can be used to regularize the solution and references to ...known algorithms are made. The adaptive filters are suitable for implementation in real-time and by simulation with an adaptive line enhancer (ALE), it is shown how the parameters of the estimation problem affect the convergence of the adaptive filter. The adaptive line enhancer (ALE) is a widely used adaptive filter to separate periodic signals from additive background noise where it has traditionally been implemented using the least-mean-square (LMS) or recursive-least-square (RLS) filter. The derived algorithms can generally be used in any adaptive filter application with a desired target signal.
PDF
