The Majority of Myeloma Patients Are Vitamin D Deficient, Unrelated to Survival or Cytogenetics

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5336-5336 ◽  
Author(s):  
Samantha Hudzik ◽  
Beau Snoad ◽  
Luay Mousa ◽  
Douglas W Sborov ◽  
Nita Williams ◽  
...  

Abstract Introduction: Since a link between solar radiation, vitamin D production, and decreased colon cancer mortality was established in 1980, there has been increasing interest in vitamin D and cancer, suggesting that higher vitamin D levels improve overall survival, specifically in breast and colorectal cancer (Maalmi H et al, Eur J Canc, May-2014, PMID 24582912), but also in follicular lymphoma (Kelly JL, J Clin Onc, 1-May-2015, PMID 25823738). In myeloma, largest published series is from the Mayo Clinic reporting on 148 newly diagnosed MM patients for which no survival association was found, but there were associations between low 25-OH-Vit D (<20 ng/mL) and higher serum CRP, serum creatinine, and ISS stage (Ng AC, Am J. Heme, Jul-2009, PMID 19415724); we wanted to expand on their trailblazing analysis. Cytogenetically high risk myeloma characterized by the amplification of 1q21 is associated with increased serum levels of soluble IL-6 receptor (sIL-6r) (Stephens OW, Blood, 2012, PMID 22072558) which may be associated with other markers of inflammation, e.g. CRP, creatinine, and b2microglobulin. Methods: The Buckeye Myeloma Registry (OSU 10115) opened in 2011 to enroll any patient with a plasma cell dyscrasia. Serum total 25-OH-Vitamin D was measured at the time of the initial clinic visit to the myeloma group at Ohio State. Results: Of a total of 843 patients, 115 (13.6%), 53 (6.3%) with SMM, and 675 (80.1%) with MM. In the 675 MM patients, the median age was 64 y.o. (range 28-95), 14.5% African-American and the remainder Caucasian, with 28.6% ISS stage 1, 48.7% ISS stage 2, 21.9% ISS stage 3, and 24.5% unknown. At diagnosis for the MM patients, 67% presented with lytic bone disease. Out of 675 MM patients, there were 52 (7.7%) patients with < 10 ng/mL 25-OH-Vit D, 394 (51%) with low vit D (10-30 ng/mL), and 229 (39%) for 25-OH-Vit D 30-100 ng/mL. There was no correlation between 25-OH-Vit D and BMI or creatinine, but there was a strong correlation with race (r=0.18, p<0.000026). Among the MM patients, log-rank [Mantel-Cox] analysis of overall survival with serum 25-OH-Vit D including all groups demonstrated no significant differences (p=0.9725) with only 101 events. There was no correlation between 25-OH-Vit D and the presence on CD138-selected FISH of 1q21 amplification (p=0.196), 17p (p53) deletion (p=0.68), or 13q deletion (p=0.812). Conclusion: The majority of myeloma patients are vitamin D deficient, but this was not associated with worsened overall survival or with high risk cytogenetics. Cox proportional hazards analyses of survival adjusted for significant univariate covariates will be presented at the meeting. Correlations with presence or absence of diffuse lytic bone disease, severity of renal insufficiency, and race will also be presented at the meeting. Disclosures No relevant conflicts of interest to declare.

Author(s):  
Mariam El-Zein ◽  
Farzin Khosrow-Khavar ◽  
Ann N Burchell ◽  
Pierre-Paul Tellier ◽  
Shaun Eintracht ◽  
...  

Abstract Background We assessed the association between serum 25-hydroxyvitamin D levels and genital human papillomavirus (HPV) prevalence, incidence, and clearance among female participants of the HITCH cohort study. Methods We genotyped HPV DNA in vaginal samples and quantified baseline serum 25-hydroxyvitamin D levels using Roche’s Linear Array and Total vitamin D assay, respectively. We used logistic and Cox proportional hazards models to respectively estimate adjusted odds ratios (OR) and hazards ratios (HR) with 95% confidence intervals (CI). Results There was no association between vitamin D levels (every 10ng/mL increase) at baseline and HPV prevalence (OR=0.88, CI:0.73-1.03) or incidence (HR=0.88, CI:0.73-1.06), but we observed a modest negative association with HPV clearance (HR=0.76, CI:0.60-0.96). Vitamin D levels &lt;30ng/mL, compared to ≥30ng/mL, were not associated with HPV prevalence (OR=0.98, CI:0.57-1.69) or incidence (HR=0.87, CI:0.50-1.43), but were associated with a marginally significant increased clearance (OR=2.14, CI:0.99-4.64). We observed consistent results with restricted cubic spline modelling of vitamin D levels and clinically defined categories. HPV type-specific analyses accounting for multiple HPV infections per participant showed no association between vitamin D levels and all study outcomes. Conclusion This study provided no evidence of an association between low vitamin D levels and increased HPV prevalence, acquisition, or clearance.


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4847-4847
Author(s):  
Mats Jerkeman ◽  
Elisabeth Székely ◽  
Oskar Hagberg ◽  
Ola Linden

Abstract Abstract 4847 Background Low levels of circulating 25-hydroxyvitamin D [25(OH)D] has been associated with inferior EFS and OS in DLBCL[1]. Ultraviolet B radiation from the sun contributes strongly to the vitamin D status in humans. In Scandinavia, the difference in sun light exposure is highly dependent on season. Consequently, vitamin D levels in Norway have been found to be 15–50 % lower in winter compared to summer[2]. In this study we tested the hypothesis that diagnosis of DLBCL during the lighter period of the year may be related to superior overall survival in DLBCL. Patients and materials The study population was collected from the Swedish Lymphoma Registry 2000–2010. A Cox regression model was analyzed for overall survival. Light exposure was defined as a continuous variable - cos((month of diagnosis -6)/12 × 2π) – varying between -1 in December and +1 in June. In addition, age, stage, year of diagnosis, performance status, number of extranodal sites, and LDH were included as cofactors. Results During this period, 5268 adult patients with DLBCL were identified. In multivariate analysis, including all factors above, overall survival was significantly superior for patients diagnosed during the lighter part of the year, p = 0.032. The hazard ratio for death due to all causes for patients diagnosed in June compared to December was 0.90. Monthly Discussion On a population level, seasonal differences in sun light exposure may contribute to differences in overall survival in DLBCL. However, to prove if normalizing vitamin D levels in this group of patients would improve survival; this will require testing in randomized trials. Disclosures: No relevant conflicts of interest to declare.


2021 ◽  
Vol 9 (7) ◽  
pp. e002417
Author(s):  
Riyue Bao ◽  
Stefani Spranger ◽  
Kyle Hernandez ◽  
Yuanyuan Zha ◽  
Peter Pytel ◽  
...  

BackgroundTumor-infiltrating CD8+ T cells and neoantigens are predictors of a favorable prognosis and response to immunotherapy with checkpoint inhibitors in many types of adult cancer, but little is known about their role in pediatric malignancies. Here, we analyzed the prognostic strength of T cell-inflamed gene expression and neoantigen load in high-risk neuroblastoma. We also compared transcriptional programs in T cell-inflamed and non-T cell-inflamed high-risk neuroblastomas to investigate possible mechanisms of immune exclusion.MethodsA defined T cell-inflamed gene expression signature was used to categorize high-risk neuroblastomas in the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) program (n=123), and the Gabriella Miller Kids First (GMKF) program (n=48) into T cell-inflamed, non-T cell-inflamed, and intermediate groups. Associations between the T cell-inflamed and non-T cell-inflamed group, MYCN amplification, and survival were analyzed by Cox proportional hazards models. Additional survival analysis was conducted after integrating neoantigen load predicted from somatic mutations. Pathways activated in non-T cell-inflamed relative to T cell-inflamed tumors were analyzed using causal network analysis.ResultsPatients with T cell-inflamed high-risk tumors showed improved overall survival compared with those with non-T cell-inflamed tumors (p<0.05), independent of MYCN amplification status, in both TARGET and GMKF cohorts. Higher neoantigen load was also associated with better event-free and overall survival (p<0.005) and was independent of the T cell-inflamed signature. Activation of MYCN, ASCL1, SOX11, and KMT2A transcriptional programs was inversely correlated with the T cell-inflamed signature in both cohorts.ConclusionsOur results indicate that tumors from children with high-risk neuroblastoma harboring a strong T cell-inflamed signature have a more favorable clinical outcome, and neoantigen load is a prognosis predictor, independent of T cell inflammation. Strategies to target SOX11 and other signaling pathways associated with non-T cell-inflamed tumors should be pursued as potential immune-potentiating interventions.


Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Sebastian K Khoo ◽  
Jayne Y Tan ◽  
Leonard Y Yeo ◽  
Prakash Paliwal ◽  
Hock L Teoh ◽  
...  

Introduction: Vitamin D deficiency has been implicated in vascular dysfunction and the risk of recurrent vascular events. Previous studies, limited by a small sample size and lack of comparisons with long-term events, have yielded discordant results. To assess the hypothesis that low vitamin D levels predict long-term vascular events in patients with ischemic stroke, we conducted a large hospital-based study to compare the association between baseline vitamin D levels and the subsequent risk of vascular events. Methods: Between January 2010 and July 2011, 590 participants (mean age, 60.7 years; 69% men) diagnosed with ischemic stroke and transient ischemic attack at the National University Hospital, Singapore, were prospectively followed for vascular events (recurrent stroke, myocardial infarction and vascular death). Serum 25-hydroxyvitamin D levels were determined using the Roche Cobas e411 analyzer. Cox proportional hazards models were used to assess the associations between quartiles of serum 25-hydroxyvitamin D and the risk of vascular events, which were adjusted for demographic, stroke severity and subtype, and vascular risk factor covariates. Results: During a mean follow-up of 3.2 years (1,190 person-year), 116 participants developed a recurrent vascular event (recurrent stroke, n=63; myocardial infarction, n=30; vascular death, n=23). Using Cox proportional hazards models, the multivariate adjusted hazard ratios (95% confidence interval) for recurrent vascular events in participants with lower levels of serum 25-hydroxyvitamin D (<14.9 mmol/l, 14.9-21.4 mmol/l and 21.5-28.9 mmol/l) were 1.43 (0.81-2.55), 1.70 (0.97-2.91) and 2.09 (1.22-3.58) compared to participants with higher concentrations (>28.9 mmol/l). Kaplan-Meier plots for unadjusted rates of vascular events show clear differences in risk by quartiles of serum 25-hydroxyvitamin D after a year of follow-up. Conclusions: Our results support the association between vitamin D deficiency and increased risk of recurrent vascular events in patients with ischemic stroke. Clinical trials are needed to ascertain whether correcting for this deficiency could indeed reduce the burden of vascular events in these individuals.


Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Andrea L Schneider ◽  
Pamela L Lutsey ◽  
Alvaro Alonso ◽  
Rebecca F Gottesman ◽  
A R Sharrett ◽  
...  

Introduction: Recent studies, mainly performed in elderly whites, suggest that vitamin D, measured by 25-hydroxyvitamin D [25(OH)D], is important for cognition. Less is known about the association of 25(OH)D measured in mid-life with cognition and dementia risk in whites and blacks. Hypothesis: We hypothesized that lower concentrations of 25(OH)D would be associated cross-sectionally with lower cognitive test scores and prospectively with greater decline in cognitive test scores and with increased risk of dementia. Methods: We conducted cross-sectional (1993-1995), change (1993-1995 to 2004-2006), and prospective (follow-up through 2010) analyses of 1,652 participants in the ARIC Brain Ancillary Study with measured 25(OH)D (1993-1995). 25(OH)D was analyzed in race-specific tertiles and continuously. Cognition was measured by 3 tests: Delayed Word Recall (DWR), Digit Symbol Substitution (DSS), and Word Fluency (WF). Dementia was defined by hospitalization ICD-9 codes. Adjusted race-stratified linear regression and Cox proportional hazards models were used. Results: Mean age of participants was 62 years, 60% were female, and 48% were black. Mean 25(OH)D was higher in whites than blacks (25.5 versus 17.3 ng/ml, p<0.05). Over a median of 16.6 years, there were 145 incident hospitalized dementia cases. In prospective analyses, lower levels of 25(OH)D trended towards an association with increased dementia risk in whites and in blacks, but these results were not statistically significant (lowest versus highest tertile: whites, HR: 1.32 [95% CI: 0.69, 2.55]; blacks, HR: 1.53 [95% CI: 0.84, 2.79]) (Figure). Conclusion: In contrast to prior studies performed in elderly populations, our study did not find significant associations between lower levels of 25(OH)D in mid-life with lower cognitive test scores at baseline, change in score over time, or increased dementia risk.


2013 ◽  
Author(s):  
Adodra Annika ◽  
Kouklinos Andreas ◽  
Julies Priscilla ◽  
Shaw Mathew ◽  
Jacobs Benjamin

Author(s):  
Claudius E. Degro ◽  
Richard Strozynski ◽  
Florian N. Loch ◽  
Christian Schineis ◽  
Fiona Speichinger ◽  
...  

Abstract Purpose Colorectal cancer revealed over the last decades a remarkable shift with an increasing proportion of a right- compared to a left-sided tumor location. In the current study, we aimed to disclose clinicopathological differences between right- and left-sided colon cancer (rCC and lCC) with respect to mortality and outcome predictors. Methods In total, 417 patients with colon cancer stage I–IV were analyzed in the present retrospective single-center study. Survival rates were assessed using the Kaplan–Meier method and uni/multivariate analyses were performed with a Cox proportional hazards regression model. Results Our study showed no significant difference of the overall survival between rCC and lCC stage I–IV (p = 0.354). Multivariate analysis revealed in the rCC cohort the worst outcome for ASA (American Society of Anesthesiologists) score IV patients (hazard ratio [HR]: 16.0; CI 95%: 2.1–123.5), CEA (carcinoembryonic antigen) blood level > 100 µg/l (HR: 3.3; CI 95%: 1.2–9.0), increased lymph node ratio of 0.6–1.0 (HR: 5.3; CI 95%: 1.7–16.1), and grade 4 tumors (G4) (HR: 120.6; CI 95%: 6.7–2179.6) whereas in the lCC population, ASA score IV (HR: 8.9; CI 95%: 0.9–91.9), CEA blood level 20.1–100 µg/l (HR: 5.4; CI 95%: 2.4–12.4), conversion to laparotomy (HR: 14.1; CI 95%: 4.0–49.0), and severe surgical complications (Clavien-Dindo III–IV) (HR: 2.9; CI 95%: 1.5–5.5) were identified as predictors of a diminished overall survival. Conclusion Laterality disclosed no significant effect on the overall prognosis of colon cancer patients. However, group differences and distinct survival predictors could be identified in rCC and lCC patients.


2018 ◽  
Vol 100-B (5) ◽  
pp. 652-661 ◽  
Author(s):  
J. M. Lawrenz ◽  
J. F. Styron ◽  
M. Parry ◽  
R. J. Grimer ◽  
N. W. Mesko

Aims The primary aim of this study was to determine the effect of the duration of symptoms (DOS) prior to diagnosis on the overall survival in patients with a primary bone sarcoma. Patients and Methods In a retrospective analysis of a sarcoma database at a single institution between 1990 and 2014, we identified 1446 patients with non-metastatic and 346 with metastatic bone sarcoma. Low-grade types of tumour were excluded. Our data included the demographics of the patients, the characteristics of the tumour, and the survival outcome of patients. Cox proportional hazards analysis and Kaplan–Meier survival analysis were performed, and the survivorship of the non-metastatic and metastatic cohorts were compared. Results In the non-metastatic cohort, a longer DOS was associated with a slightly more favourable survival (hazard ratio (HR) 0.996, 95% confidence interval (CI) 0.994 to 0.998, p < 0.001). In all types of tumour, there was no difference in survival between patients with a DOS of greater than four months and those with a DOS of less than four months (p = 0.566). There was no correlation between the year of diagnosis and survival (p = 0.741). A diagnosis of chondrosarcoma (HR 0.636, 95% CI 0.474 to 0.854, p = 0.003) had the strongest positive effect on survival, while location in the axial skeleton (HR 1.76, 95% CI 1.36 to 2.29, p < 0.001) had the strongest negative effect on survival. Larger size of tumour (HR 1.05, 95% CI 1.03 to 1.06, p < 0.001) and increased age of the patient (HR 1.02, 95% CI 1.01 to 1.03, p < 0.001) had a slightly negative effect on survival. Metastatic and non-metastatic cohorts had similar median DOS (16 weeks, p = 0.277), although the median survival (15.5 months vs 41 months) and rates of survival at one year (69% vs 89%) and five years (20% vs 59%) were significantly shorter in the metastatic cohort. Conclusion A longer DOS prior to diagnosis is not associated with a poorer overall survival in patients with a primary bone sarcoma. Location in the axial skeleton remains the strongest predictor of a worse prognosis. This may be helpful in counselling patients referred for evaluation on a delayed basis. Cite this article: Bone Joint J 2018;100-B:652–61.


Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 453
Author(s):  
Yu-Han Wang ◽  
Shih-Ching Chang ◽  
Muhamad Ansar ◽  
Chin-Sheng Hung ◽  
Ruo-Kai Lin

Colorectal cancer (CRC) arises from chromosomal instability, resulting from aberrant hypermethylation in tumor suppressor genes. This study identified hypermethylated genes in CRC and investigated how they affect clinical outcomes. Methylation levels of specific genes were analyzed from The Cancer Genome Atlas dataset and 20 breast cancer, 16 esophageal cancer, 33 lung cancer, 15 uterine cancer, 504 CRC, and 9 colon polyp tissues and 102 CRC plasma samples from a Taiwanese cohort. In the Asian cohort, Eps15 homology domain-containing protein 3 (EHD3) had twofold higher methylation in 44.4% of patients with colonic polyps, 37.3% of plasma from CRC patients, and 72.6% of CRC tissues, which was connected to vascular invasion and high microsatellite instability. Furthermore, EHD3 hypermethylation was detected in other gastrointestinal cancers. In the Asian CRC cohort, low EHD3 mRNA expression was found in 45.1% of patients and was connected to lymph node metastasis. Multivariate Cox proportional-hazards survival analysis revealed that hypermethylation in women and low mRNA expression were associated with overall survival. In the Western CRC cohort, EHD3 hypermethylation was also connected to overall survival and lower chemotherapy and antimetabolite response rates. In conclusion, EHD3 hypermethylation contributes to the development of CRC in both Asian and Western populations.


Author(s):  
Anne Bukten ◽  
Marianne Riksheim Stavseth

Abstract Background People in prison have an extremely high risk of suicide. The aim of this paper is to describe all suicides in the Norwegian prison population from 2000 to 2016, during and following imprisonment; to investigate the timing of suicides; and to investigate the associations between risk of suicide and types of crime. Methods We used data from the Norwegian Prison Release study (nPRIS) including complete national register data from the Norwegian Prison Register and the Norwegian Cause of Death Register in the period 1.1.2000 to 31.12.2016, consisting of 96,856 individuals. All suicides were classified according to ICD-10 codes X60-X84. We calculated crude mortality rates (CMRs) per 100,000 person-years and used a Cox Proportional-Hazards regression model to investigate factors associated with suicide during imprisonment and after release reported as hazard ratios (HRs). Results Suicide accounted for about 10% of all deaths in the Norwegian prison population and was the leading cause of death in prison (53% of in deaths in prison). The CMR per 100,000 person years for in-prison suicides was 133.8 (CI 100.5–167.1) and was ten times higher (CMR = 1535.0, CI 397.9–2672.2) on day one of incarceration. Suicides after release (overall CMR = 82.8, CI 100.5–167.1) also peaked on day one after release (CMR = 665.7, CI 0–1419.1). Suicide in prison was strongly associated with convictions of homicide (HR 18.2, CI 6.5–50.8) and high-security prison level (HR 15.4, CI 3.6–65.0). Suicide after release was associated with convictions of homicide (HR 3.1, CI 1.7–5.5). Conclusion There is a high risk of suicide during the immediate first period of incarceration and after release. Convictions for severe violent crime, especially homicide, are associated with increased suicide risk, both in prison and after release.


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