25-OH-Vitamin-D Deficiency Impairs Rituximab-Mediated Cellular Cytotoxicity and Is Associated With An Inferior Outcome Of Elderly DLBCL Patients Treated With Rituximab

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1819-1819 ◽  
Author(s):  
Joerg Thomas Bittenbring ◽  
Bettina Altmann ◽  
Frank Neumann ◽  
Marina Achenbach ◽  
Joerg Reichrath ◽  
...  

Abstract Background To investigate the impact and underlying mechanisms of vitamin-D-deficiency (VDD) on outcome of elderly (61 to 80 year-old) DLBCL patients. Methods Pretreatment 25-OH-vitamin-D serum levels from 359 patients treated in the prospective multicenter RICOVER-60 trial with 6 or 8 cycles of CHOP-14 with and without 8 cycles rituximab and 63 patients in the RICOVER-noRT study treated with 6xCHOP-14 + 8xR were determined determined by LIASION®, a commercially available chemoluminescent immunoassay. Results RICOVER-60 patients with VDD (defined as serum levels ≤8 ng/m l) and treated with rituximab had a 3-year event-free survival of 59% compared to 79% in patients with >8 ng/ml; 3-year overall survival was 70% and 82%, respectively. These differences were significant in a multivariable analysis adjusting for IPI risk factors with a hazard ratio of 2.1 [p=0.008] for event-free survival and 1.9 [p=0.040] for overall survival. In patients treated without rituximab 3-year EFS was not significantly different in patients with vitamin-D levels ≤8 and >8 ng/ml (HR 1.2; p=0.388). These results were confirmed in an independent validation set of 63 patients treated within the RICOVER-noRT study. Rituximab-mediated cellular toxicity (RMCC) against the CD20+ cell line Daudi as determined by LDH release assay increased significantly (p<0.005) in 5/5 vitamin-D-deficient individuals after vitamin-D substitution and normalization of their vitamin-D levels. Conclusions VDD is a significant risk factor for elderly DLBCL patients treated with rituximab. Our results show that VDD impairs RMCC and that RMCC can be improved by vitamin-D substitution. This together with the differential effect of VDD in patients treated with and without rituximab suggests that vitamin-D substitution might result in a better outcome of these patients when treated with CHOP plus rituximab. Supported by a grant from Deutsche Krebshilfe. Disclosures: No relevant conflicts of interest to declare.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8569-8569
Author(s):  
Joerg Thomas Bittenbring ◽  
Marina Achenbach ◽  
Bettina Altmann ◽  
Marita Ziepert ◽  
Joerg Reichrath ◽  
...  

8569 Background: Vitamin D deficiency was shown to be is associated with a worse outcome in patients with non-Hodgkin's lymphoma (Drake et al., 2010) To study whether this observation could be confirmed in patients with aggressive B-cell lymphomas treated uniformly within a prospective trial, we analyzed 25-OH vitamin D serum levels in patients treated within the RICOVER-60 trial of the DSHNHL. Methods: 25-OH Vitamin D serum levels were determined with a commercial chemoluminescence immunoassay in the serum from elderly patients of the RICOVER-60 trial which compared 6 or 8 cycles of CHOP, both with and without rituximab. Results: 193 of 359 pts (53.8%) had vitamin D deficiency (<10 ng/ml) and 165/359 patients (46.0%) had vitamin D insufficiency (10-30 ng/ml) according to current definitions. When treated with R-CHOP, patients with vitamin D levels ≤8 ng/ml had a 3-year EFS of 59% compared to 79% of patients with vitamin D serum levels >8 ng/ml; the respective figures for 3-year overall survival were 70% and 82%, respectively. In R-CHOP pts these differences were significant in a multivariable analysis adjusting for IPI risk factors with a hazard ratio (HR) of 2.1 (p=0.008) for EFS and a HR of 1.9 (p=0.040) for OS. In pts treated without R effects of vitamin D deficiency were significant only for OS (HR 1.8; p=0.025), but not with respect to EFS (HR 1.2; p=0.388). These results were confirmed in an independent validation set of 63 patients treated within the prospective RICOVER-noRx study. Conclusions: Vitamin D deficiency is a significant risk factor for patients with aggressive B-cell lymphomas treated with R-CHOP. The stronger adverse effect of vitamin D deficiency in patients receiving rituximab suggests that vitamin D deficiency interferes with the R mechanisms of this antibody. A prospective study evaluating the effects of vitamin D substitution on outcome of patients receiving R-CHOP is warranted. Supported by Deutsche Krebshilfe.


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 690-690
Author(s):  
Gerhard Held ◽  
Samira Zeynalova ◽  
Niels Murawski ◽  
Marita Ziepert ◽  
Barbara Kempf ◽  
...  

Abstract Abstract 690 Background: There is limited information on the role of skeletal involvement in DLBCL patients treated with rituximab. Methods: In a retrospective subgroup analysis patients with aggressive B-cell lymphomas with and without skeletal involvement were compared with respect to clinical presentation, event-free and overall survival. Results: Of 3840 patients 292 (7.6%) had skeletal involvement. In a multivariable analysis of patients treated within the randomized MInT and RICOVER-60 trials, the two largest randomized trials addressing the role of rituximab in DLBCL to date, skeletal involvement was associated with a reduced hazard ratio (HR) of 0.8 (p=0.181) for event-free survival and 0.7 (p=0.083) for overall survival for patients treated without, but with an increased HR (1.5; p=0.048) for event-free and (1.1; p=0.828) for overall survival in patients treated with rituximab. This was due to the failure of rituximab to improve the outcome of patients with skeletal involvement. In the MInT trial, the 3-year EFS rates were 64% without and 63% with rituximab (p=0.680) and the 3-year OS rates were 83% without and 90% with rituximab (p=0.542). similarly, in the RICOVER-60 trial, the 3-year EFS rates were 45% without and 50% with rituximab (p=0.593) and the 3-year OS rates were 68% without and 68% with rituximab. In a Cox regression model for event-free survival adjusted for the IPI risk factors a relevant interaction (HR 1.5; p=0.056) term between rituximab and skeletal involvement was observed. In contrast to rituximab, additive radiotherapy to sites of skeletal involvement was associated with a better outcome: 3-year EFS rates were 40% without and 75% with radiotherapy (p<0.001), 3-year OS rates were 70% without and 86% with radiotherapy to sites of skeletal involvement (p=0.064). In a multivariable analysis radiotherapy reduced the risk for an event in EFS by 70% (HR=0.3; p=0.001) and by 50% in OS (HR=0.5; p=0.111). Conclusion: Addition of rituximab failed, but radiotherapy to sites of skeletal involvement did improve the outcome of DLBCL patients with skeletal involvement. Radiotherapy to sites of skeletal involvement, though abandoned by many cooperative groups world-wide, is recommended in the rituximab era, unless prospective trials demonstrate that it might be omitted in cases with a negative PET after immunochemotherapy. Disclosures: Dreyling: Roche: Membership on an entity's Board of Directors or advisory committees. Hallek:Roche: Membership on an entity's Board of Directors or advisory committees. Schmitz:Chugai: Membership on an entity's Board of Directors or advisory committees. Pfreundschuh:Roche: Membership on an entity's Board of Directors or advisory committees; Chugai: Consultancy.


Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1890-1890
Author(s):  
Sarvari Venkata Yellapragada ◽  
Anna Frolov ◽  
Nathanael Fillmore ◽  
Pallavi Dev ◽  
Sumaira Shafi ◽  
...  

Abstract Background: A number of studies have reported elevated incidence of 25-OH-vitamin D deficiency among patients with multiple myeloma (MM). Several studies have found association between vitamin D levels and factors associated with survival, including ISS stage at diagnosis. However, the impact of vitamin D deficiency on MM prognosis is not entirely clear. Also, in general, both the incidence and the impact of vitamin D deficiency differ substantially by race. Here, we investigate the impact of vitamin D deficiency on prognosis in a large and racially heterogenous patient population with MM in the Veterans Affairs (VA) system. Methods: We used the VA's nationwide Corporate Data Warehouse to identify patients diagnosed with symptomatic MM from 1999 to 2017. Various demographic and laboratory data was collected including age, race, 25-OH-vitamin D levels, and ISS stage at diagnosis as well as survival outcome data. Details of therapies received was also available which indicted similar access to all newer agents approved for myeloma for both African American (AA) and Caucasian patients. Results: We identified 15,717 patients diagnosed with MM (3353 AA and 9070 Caucasian), of whom 6675 had vitamin D measurements within 2 months of diagnosis (1959 AA and 4398 Caucasian). Median serum vitamin D levels were significantly lower among AA patients (21.8 ng/mL) than Caucasians (28.6 ng/mL; p<0.0001). No difference in median vitamin D levels was observed across ISS stage at diagnosis (p=0.7575), but a significant positive correlation (ρ=0.166; p<0.0001) was found between vitamin D levels and age at diagnosis. We evaluated the ability of serum vitamin D level to predict overall survival (OS) in patients with MM using a cut-off of 20ng/mL. Patients with vitamin D deficiency (<20ng/mL) had a significantly worse prognosis than patients with normal levels (≥20ng/mL) (Fig 1A). Specifically, median OS was 3.10 years (95% CI 2.73-3.52) for patients with vitamin D deficiency, compared to 3.91 years (95% CI 3.59-4.38) for patients with normal serum vitamin D. Univariate Cox proportional hazard analysis also showed that vitamin D deficiency is a significant predictor of OS after MM diagnosis (HR 1.24; P=0.0021), and vitamin D deficiency remained an independent predictor of OS under multivariate analysis in which adjustments were made for race, age, and stage at diagnosis (HR 1.28; P=0.0385). The analyses were repeated for AA and Caucasian patients separately. Among AA patients, serum vitamin D was not a significant predictor of OS in univariate (P=0.5096) or multivariate analysis (P=0.6923), while it was still a strong predictor among Caucasian patients in both univariate (HR 1.38; P=0.0006) and multivariate analysis (HR 1.45; P=0.0048). Median OS is 3.54 years (95% CI 2.99-5.52; n=255) for AA patients with vitamin D deficiency and 3.95 years (3.25-5.35; n=296) with normal levels. Among Caucasians, median OS is 2.71 years (2.18-3.47; n=273) for deficient and 3.87 years (3.59-4.42; n=885) for normal. Kaplan-Meier plots (Fig. 1B and 1C) illustrate the observed OS curves for the two subgroups. Since levels of vitamin D were lower in AA patients, a lower cut-off of 10 ng/mL was also tested. Even using this lower cutoff, vitamin D deficiency was not a statistically significant predictor of OS in univariate (HR 1.33; P=0.0781) or multivariate analysis (HR 1.09; P=0.7039), though the number of AA patients with vitamin D <10 ng/ML is small (n=73). Conclusions: Vitamin D deficiency is a significant predictor of survival among patients diagnosed with MM, even after accounting for race, age, and ISS stage. However, this relationship is only observed in Caucasian patients and not observed among AA patients. Studies are ongoing to evaluate impact of Vitamin D deficiency of disease presentation including bone disease as well as genetic characteristics. This investigation highlights the need to assess the underlying biological mechanism responsible for the observed impact of vitamin D deficiency across race in MM. Figure 1. Figure 1. Disclosures Yellapragada: Novartis: Employment; Celgene: Research Funding; Takeda: Research Funding. Munshi:OncoPep: Other: Board of director.


2018 ◽  
Vol 47 (2) ◽  
pp. 765-771 ◽  
Author(s):  
Canser Yilmaz Demir ◽  
Muhammet Eren Ersoz

Objective To assess vitamin D, parathyroid hormone, calcitonin, calcium, phosphorus and magnesium levels in patients with versus without temporomandibular disorders (TMDs). Methods This prospective observational study included patients with TMDs and age-matched healthy controls. TMDs were diagnosed via physical and radiologic examination, and serum levels of 25 (OH) vitamin D, parathyroid hormone, calcitonin, calcium, magnesium, and phosphorus were determined. The impact of age, sex and seasonal variations in serum 25 (OH) vitamin D levels was controlled by the inclusion of age, sex and date-matched control patients. Results The study included 100 patients, comprising 50 patients with TMDs and 50 control patients. No statistically significant between-group differences were found regarding age or sex. No statistically significant between-group differences were found in terms of serum 25 (OH) vitamin D, calcitonin, calcium, magnesium or phosphorus levels. Parathyroid hormone levels were statistically significantly higher in patients with TMDs versus healthy control patients. Conclusion In patients with temporomandibular disorders, increased parathyroid hormone levels in response to vitamin D deficiency was significantly more prominent. These data suggest that, in patients with temporomandibular disorders, vitamin D deficiency should be assessed and corrected.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1952-1952
Author(s):  
Matthew T Drake ◽  
Matthew J Maurer ◽  
Brian K Link ◽  
Ivana N Micallef ◽  
Thomas M Habermann ◽  
...  

Abstract Abstract 1952 Poster Board I-975 Background: Vitamin D is a naturally occurring steroid hormone. In addition to its well-established role in maintaining serum calcium homeostasis, vitamin D has effects on cellular differentiation, proliferation, apoptosis, and angiogenesis. Vitamin D3 is naturally produced in skin in response ultraviolet-B (UVB) radiation from the sun. Several recent studies, however, have shown that a high proportion of community-dwelling subjects in both tropical and temperate climates are deficient in vitamin D, and that subjects in northern latitudes often require dietary supplementation to maintain vitamin D sufficiency. Further, several reports now suggest that vitamin D sufficiency is protective against the development of several cancers, including non-Hodgkin lymphoma (NHL). However, it is not known whether vitamin D impacts prognosis in diffuse large B-cell lymphoma (DLBCL), the most common NHL subtype. Methods: We evaluated serum vitamin D concentrations in two cohorts of DLBCL patients. The first cohort consisted of 374 patients newly diagnosed from September 2002-February 2008 who were prospectively enrolled in the University of Iowa/Mayo Clinic Lymphoma SPORE Molecular Epidemiology Resource, an observational study in which neither therapeutic nor diagnostic management is prescribed. All serum was obtained within 120 days of diagnosis, and was prior to treatment in 221 (59%). In the second study, 62 patients newly diagnosed from February 2006-August 2007 were enrolled on NCCTG clinical trial N0489, and all serum was obtained before the first course of therapy. Central pathology review was performed on all patients to confirm the diagnosis of DLBCL. Serum 25-hydroxyvitamin (25-OH-VitD) levels were measured by the gold standard method for vitamin D determination: liquid chromatography tandem mass spectroscopy (LC-MS/MS). Vitamin D deficiency was defined as total serum 25-OH-VitD < 25 ng/mL (62.5 nmol/L). SPORE patients were followed per a standard protocol for event-free (progression, retreatment, or death due to any cause) and overall survival (EFS and OS, respectively); N0489 patients were followed in a similar way per the clinical trial protocol. We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CI). Results: SPORE patients were primarily treated with immunochemotherapy (83%); all N0489 patients were treated with epratuzumab + R-CHOP21. The median age at diagnosis was 62 years (range, 19-93) for SPORE patients and 61 years (range, 21-82) for N0489 patients. Median follow-up for SPORE patients was 36 months (range, 1-77) with 95 deaths and 131 events; median follow-up for N0489 patients was 24 months (range, 7-39) with 13 deaths and 18 events. Vitamin D deficiency was identified in 188 SPORE patients (50%) and 15 N0489 patients (24%). There were no differences in the prevalence of vitamin D deficiency by age, IPI, or whether serum was obtained prior to starting treatment (all p > 0.28). Vitamin D deficiency was associated with inferior overall (HR=2.33, 95% CI 1.53-3.57, logrank p = 0.0001) and event-free survival (HR=1.71, 95% CI 1.20-2.44, logrank p = 0.003) in the SPORE cohort. These associations remained significant after adjusting for IPI and treatment: OS HR=1.97, 95% CI 1.27-3.07; EFS HR=1.47, 95% CI 1.02-2.21. These results were similar for the subset of SPORE patients who were treated with R-CHOP. The HRs for vitamin D deficiency and event-free survival were consistent in the N0489 patients (HR=1.63, 95% CI 0.61-4.35, IPI adjusted HR=1.43, 95% CI 0.53-3.85), although these results lacked precision due to a smaller sample size. We were unable to evaluate OS in N0489 due to the small number of deaths. Conclusions: Approximately 50% of all DLBCL patients in this northern US latitude population are vitamin D deficient at the time of diagnosis and treatment. Vitamin D deficient patients have an inferior event-free and overall survival compared to patients with vitamin D levels within the normal range. Vitamin D supplementation during treatment of DLBCL patients with vitamin D deficiency should be evaluated in a clinical trial setting. Disclosures: No relevant conflicts of interest to declare.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 9586-9586
Author(s):  
C. Gilmore ◽  
J. James ◽  
B. Zubal ◽  
D. Thomas ◽  
B. Tan

9586 Background: Vitamin (vit) D dficiency is prevalent amongst patients (pts) with colorectal and pancreatic cancers. Data for other GI malignancies are limited and the impact of short-course vit D supplementation is unclear. Methods: An IRB-approved retrospective review of 202 pts with GI cancers from 12/2007 to 9/2008 was done to evaluate the incidence of vitamin D deficiency defined as serum 25-OH vit D levels of ≤ 30 ng/ml (severe=<10 ng/ml; moderate=10–20 ng/ml; mild=21–30 ng/ml) and incidence of ‘low-normal' (31–50 ng/ml) and normal (>50 ng/ml) vit D levels. Oral supplementation with vit D at 50,000 ‘u' weekly x 8–12 weeks were done and serum levels were redrawn at 2–3 months for pts with low normal and deficient vit D, respectively. Results: 87.6% of all 202 pts is vit D deficient (61% severe to moderate). (see Table ). 92 pts were re-evaluated after 2–3 months of oral vit D supplementation. Among this cohort, the incidence of pts with vitamin deficiency decreased from 91.3% to 57.6% after first re- evaluation. Severe/moderate deficiency rates also decreased from 71.7% to 13%. There were no significant difference in response between males/females, age < or ≥ 65, caucasian or non-caucasian or tumor type. Conclusions: Vitamin D levels should routinely be evaluated for patients with GI maligancies. Oral supplementation decreases the rate 'any' vit D deficiency from 91% to 57%, and of 'severe to moderate' deficiency from 72% to 13%. Prospective studies on the impact of vit D deficiency and supplementation on various clinical outcomes among patients with GI cancers would improve supportive care management of these patients. [Table: see text] No significant financial relationships to disclose.


Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Eun Kyeung Song ◽  
Seok-Min Kang ◽  
Debra K Moser ◽  
Terry A Lennie

Introduction. Low levels of vitamin D and severe depressive symptoms have been associated with increased proinflammatory cytokines that predict cardiovascular disease. However, little is known about the relationships among depressive symptoms, vitamin D deficiency, and cardiac events in patients with heart failure (HF). Hypothesis. We hypothesized that the link of depressive symptoms to cardiac event-free survival would differ between patients with vitamin D adequacy and deficiency. Methods. A total of 232 patients with HF (age 66±8 years, 34% female) completed the Patient Health Questionnaire-9 to assess depressive symptoms and were split into 2 groups using the standard PHQ-9 cutoff point of 10. Nutrition Analysis program was used to determine average daily intake of vitamin D through a 3-day food diary. Patients with > 85% probability of deficiency were defined as having a diet deficient in vitamin D. Covariate data on age, gender, body mass index, NYHA class, ejection fraction, comorbidities, and prescribed medications were obtained from review of medical records. Patients were followed for 2 years to determine time to first event of hospitalization or death. Hierarchical Cox proportional regression was used to examine our hypothesis. Results. 106 patients (46%) had depressive symptoms and 116 patients (50%) had vitamin D deficiency. During 2 years, 88 patients (38%) were hospitalized or died due to cardiac problems. Depressive symptoms were associated with vitamin D deficiency ( X 2 =4.45, p = .035). In patients with vitamin D deficiency, depressive symptoms (HR=2.56, 95% CI=1.28-5.21) predicted shorter event-free survival after controlling for all covariates, whereas there was no difference in cardiac event-free survival between patients with depressive symptoms and no depressive symptoms in patients with vitamin D adequacy ( p = .185) . Conclusions. The data suggest that depressive symptoms were not associated with cardiac event-free survival in HF patients with adequate intake of vitamin D. Future study is required to determine whether vitamin D adequacy could play a protective role in the impact of depressive symptoms on cardiac event-free survival in patients with HF.


Author(s):  
Nazanin Alavi ◽  
Mahbod Ebrahimi ◽  
Firoozeh Akbari-Asbagh

Background: Vitamin D deficiency and infertility are two important health problems in Iran. Some studies suggest that vitamin D may influence Anti-Müllerian hormone (AMH) and antral follicle count (AFC) as an ovarian reserve. Objective: The present study aimed to investigate the impact of vitamin D on AMH serum concentrations/AFC. Materials and Methods: three hundred and five infertile women referred to the IVF Unit of Yas hospital, between July and December 2017, were enrolled in this cross-sectional study. The demographic characteristics of the participants, as well as the serum levels of vitamin D, AMH, and ultrasonic examination of AFC were recorded. Results: Finally, 287 infertile women were included in the analysis with a mean age of 29.95 ± 4.73 yr (18-45 yr) and a mean Body mass indexof 25.11 ± 4.41 kg/m2. The median AMH and vitamin D levels were 3.20 and 22.82 ng/ml, respectively. Considering the cut-off level of 20 ng/ml, 58.7% were vitamin D deficient. Regression analysis showed no association between AMH and vitamin D levels (p = 0.161), even after adjusting for baseline variables (p = 0.182). A total of 120 patients had an AFC < 6 and 164 ≥ 6, which was not statistically different between the groups with normal level or deficient vitamin D (p = 0.133). Conclusion: The present cross-sectional study showed no significant association between serum levels of vitamin D and AMH or AFC in infertile women, even after adjusting for baseline variables. Key words: Anti-Müllerian hormone, Infertility, Vitamin D deficiency, Ovarian follicle.


2017 ◽  
Vol 75 (1) ◽  
pp. 3-8 ◽  
Author(s):  
Yara Dadalti Fragoso ◽  
Tarso Adoni ◽  
Soniza Vieira Alves-Leon ◽  
Samira L. Apostolos-Pereira ◽  
Walter Oleschko Arruda ◽  
...  

ABSTRACT Objective: Vitamin D has taken center stage in research and treatment of multiple sclerosis (MS). The objective of the present study was to assess the serum vitamin D levels of a large population of patients with MS and controls living in a restricted tropical area. Methods: Data from 535 patients with MS and 350 control subjects were obtained from 14 cities around the Tropic of Capricorn. Results: The mean serum 25-OH vitamin D level was 26.07 ± 10.27 ng/mL for the control subjects, and 28.03 ± 12.19 ng/mL for patients with MS. No correlation was observed between vitamin D levels and the disability of patients over the disease duration. Conclusion: At least for the region around the Tropic of Capricorn, serum levels of vitamin D typically are within the range of 20 to 30 ng/mL for controls and patients with MS.


Author(s):  
Chandralekha Ashangari ◽  
Amer Suleman

Objectives The aim of this study is to assess vitamin D levels, including the prevalence of vitamin D deficiency/insufficiency in Postural Orthostatic Tachycardia Syndrome (POTS) patients. Background : The Postural Orthostatic Tachycardia Syndrome (POTS) affects primarily young women. POTS is a form of dysautonomia that is estimated to impact between 1,000,000 and 3,000,000 Americans, and millions more around the world. We frequently find vitamin D deficiency in patients who present with POTS Methods: 180 patients were selected randomly from our clinic with POTS. Patients Vitamin D levels charts were reviewed from electronic medical records, 25-OH vitamin D (Vitamin D3 ) status was defined as Normal (>30 ng/mL), Insufficient (20.0-29.9 ng/mL), and deficient (<20 ng/mL). Results: Out of 180 patients, 170 patients are female (94%, n=170, age 31.88±10.36), 10 patients are male (6% ,age 25.83±6.19). 79 patients had vitamin D3 level >30 ng/ml, 10 patients had vitamin D3 level range >20.0 to 29.9 ng/mL, 91 patients had vitamin D3 level < 20ng/mL. Conclusion: Our research results demonstrated that Postural Orthostatic Tachycardia Syndrome (POTS) patients have a higher rate of vitamin D3 deficiency (51% have Vitamin D3 less than 20 ng/mL). Vitamin D3 levels are low in more than half of POTS patients (56% had less than 30 ng/mL )


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