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1.
Medicine (Baltimore) ; 98(48): e18113, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31770235

RESUMO

The impact of vitamin D deficiency on the recovery of patients with malnutrition remains undefined. Our aim was to study the prevalence of vitamin D deficiency in a well-characterized cohort of patients with malnutrition and its association with outcomes.Within this secondary analysis of a randomized controlled trial, we examined the association of vitamin D deficiency and adverse clinical outcomes over a follow-up of 180 days in hospitalized patients at risk for malnutrition. We measured 25-hydroxyvitamin D levels upon admission and defined Vitamin D deficiency when levels were <50nmol/l. The primary endpoint was 180-day mortality.The prevalence of vitamin D deficiency in our cohort of 828 patients was 58.2% (n = 482). Patients with vitamin D deficiency had increased 180-day mortality rates from 23.1% to 29.9% (odds ratio 1.42, 95% confidence interval [CI] 1.03-1.94, P = .03). When adjusting the analysis for demographics, comorbidities, and randomization, this association remained significant for the subgroup of patients not receiving vitamin D treatment (adjusted odds ratio 1.63, 95% CI 1.01-2.62, P = .04). There was no significantly lower risk for mortality in the subgroup of vitamin D deficient patients receiving vitamin D treatment compared to not receiving treatment (adjusted odds ratio 0.74, 95% CI 0.48-1.13, P = .15).Vitamin D deficiency is highly prevalent in the population of malnourished inpatients and is negatively associated with long-term mortality particularly when patients are not receiving vitamin D treatment. Our findings suggest that malnourished patients might benefit from vitamin D screening and treatment in case of deficiency.


Assuntos
Idoso Fragilizado/estatística & dados numéricos , Fragilidade/mortalidade , Desnutrição/mortalidade , Deficiência de Vitamina D/mortalidade , Deficiência de Vitamina D/terapia , Idoso , Idoso de 80 Anos ou mais , Suplementos Nutricionais , Feminino , Fragilidade/sangue , Fragilidade/complicações , Humanos , Pacientes Internados/estatística & dados numéricos , Masculino , Desnutrição/sangue , Desnutrição/complicações , Prevalência , Estudos Prospectivos , Qualidade de Vida , Resultado do Tratamento , Vitamina D/análogos & derivados , Vitamina D/sangue , Vitamina D/uso terapêutico , Deficiência de Vitamina D/complicações , Vitaminas/uso terapêutico
2.
Crit Care ; 23(1): 200, 2019 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-31164148

RESUMO

BACKGROUND: Vitamin D supplementation has shown promise for reducing mortality in the intensive care setting. As a steroid prohormone with pleiotropic effects, there may be a lag between administration and observing clinical benefit. This secondary analysis of the VITdAL-ICU study sought to explore whether the effect size of vitamin D on mortality was different when study participants who died or were discharged early were excluded. METHODS: The VITdAL-ICU study was a randomized, placebo-controlled trial in critically ill adults who received placebo or 540,000 IU cholecalciferol followed by monthly supplementation. The effect of vitamin D on 28-day mortality was evaluated after exclusion of participants who died or were discharged within 7 days from study drug administration, according to vitamin D concentrations on day 3, using a bivariate analysis adjusted for confounders and in a stepwise multiple analysis. RESULTS: Of 475 study participants, 65 died or were discharged within the first 7 days. In the remaining 410 patients, vitamin D supplementation was associated with a reduction in 28-day mortality [OR 0.58 (95% CI 0.35-0.97) p value = 0.035]. The effect on mortality was not significant after adjusting for age, severity scores, female gender, chronic liver and kidney disease, COPD, diagnosis of the tumor, mechanical ventilation, and vasopressors at enrollment (all p > 0.05). In a multiple model, the mortality reduction by vitamin D supplementation did not remain independently significant [OR 0.61 (95% CI 0.35-1.05) p = 0.075]. Vitamin D metabolite response, in the treatment group, demonstrated that survivors at 28 days, had higher levels of 25-hydroxyvitamin D (34.4 vs 25.4 ng/ml, p = 0.010) and 1,25-dihydroxyvitamin D (107.6 vs 70.3 pg/ml, p = 0.049) on day 3. The increase of plasma metabolites after vitamin D oral supplementation, independent of the baseline value, was associated with lower odds of death [OR 0.48 (95% CI 0.27-0.87) p value = 0.016]. CONCLUSIONS: High-dose vitamin D3 supplementation was associated with a reduction of 28-day mortality in a mixed population of critically ill adults with vitamin D deficiency when excluding patients who died or were discharged within 7 days after study inclusion. However, this survival benefit was not independently confirmed when adjusted for other factors strongly associated with mortality.


Assuntos
Mortalidade/tendências , Vitamina D/farmacologia , Idoso , Idoso de 80 Anos ou mais , Estado Terminal/mortalidade , Estado Terminal/terapia , Método Duplo-Cego , Feminino , Humanos , Unidades de Terapia Intensiva/organização & administração , Unidades de Terapia Intensiva/estatística & dados numéricos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Placebos , Análise de Sobrevida , Vitamina D/sangue , Vitamina D/uso terapêutico , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/mortalidade , Vitaminas/farmacologia , Vitaminas/uso terapêutico
3.
Artigo em Inglês | MEDLINE | ID: mdl-30700025

RESUMO

Epidemiological evidence suggests that vitamin D deficiency is associated with increased mortality, but it is unclear whether this is explained by reverse causation, and if there are specific causes of death for which vitamin D might be important. We conducted a systematic review of observational studies investigating associations between circulating 25-hydroxyvitamin D (25(OH)D) concentration and all-cause or cause-specific mortality in generally healthy populations. Relevant studies were identified using PubMed and EMBASE searches. After screening 722 unique records and removing those that were ineligible, 84 articles were included in this review. The vast majority of studies reported inverse associations between 25(OH)D concentration and all-cause mortality. This association appeared to be non-linear, with progressively lower mortality with increasing 25(OH)D up to a point, beyond which there was no further decrease. There is moderate evidence that vitamin D status is inversely associated with cancer mortality and death due to respiratory diseases, while for cardiovascular mortality, there is weak evidence of an association in observational studies, which is not supported by the data from intervention or Mendelian randomization studies. The relationship between vitamin D status and other causes of death remains uncertain due to limited data. Larger long-term studies are required to clarify these associations.


Assuntos
Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/mortalidade , Vitamina D/análogos & derivados , Vitaminas/sangue , Estudos Observacionais como Assunto , Vitamina D/sangue
4.
Eur J Nutr ; 58(6): 2535-2543, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30121806

RESUMO

PURPOSE: Low 25-hydroxyvitamin D (25[OH]D) concentrations have been associated with adverse outcomes in selected populations with established chronic heart failure (CHF). However, it remains unclear whether 25[OH]D deficiency is associated with mortality and hospitalisation in unselected patients receiving contemporary medical and device therapy for CHF. METHODS: We prospectively examined the prevalence and correlates of 25[OH]D deficiency in 1802 ambulatory patients with CHF due to left ventricular systolic dysfunction (left ventricular ejection fraction ≤ 45%) attending heart failure clinics in the north of England. RESULTS: 73% of patients were deficient in 25[OH]D (< 50 nmol/L). 25[OH]D deficiency was associated with male sex, diabetes, lower serum sodium, higher heart rate, and greater diuretic requirement. During a mean follow-up period of 4 years, each 2.72-fold increment in 25[OH]D concentration (for example from 32 to 87 nmol/L) is associated with 14% lower all-cause mortality (95% confidence interval (CI) 1, 26%; p = 0.04), after accounting for potential confounding factors. CONCLUSIONS: Low 25-hydroxyvitamin D deficiency is associated with increased mortality in patients with chronic heart failure due to left ventricular systolic dysfunction. Whether vitamin D supplementation will improve outcomes is, as yet, unproven.


Assuntos
Insuficiência Cardíaca/mortalidade , Deficiência de Vitamina D/mortalidade , Idoso , Doença Crônica , Estudos de Coortes , Comorbidade , Inglaterra/epidemiologia , Feminino , Seguimentos , Insuficiência Cardíaca/sangue , Humanos , Masculino , Prevalência , Estudos Prospectivos , Fatores Sexuais , Vitamina D/análogos & derivados , Vitamina D/sangue , Deficiência de Vitamina D/sangue
5.
J Gerontol A Biol Sci Med Sci ; 74(1): 121-128, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30371905

RESUMO

Background: A strong association of serum 25-hydroxyvitamin-D levels (25(OH)D) with all-cause mortality has been shown previously and 25(OH)D could be a useful aging marker. Methods: The analysis was performed in a population-based, cohort study from Germany with 9,940 participants, aged 50-74 years at baseline. A general linear model was used to assess associations of 25(OH)D levels with chronological age and the aging markers leukocyte telomere length (LTL), epigenetic age acceleration, and 8-isoprostane levels. A multivariate Cox regression model was applied to explore the independent and combined associations of these biomarkers with all-cause mortality (2,204 deaths occurred during a median follow-up of 14.3 years). Results: On average, study participants lost 2.9 nmol/L 25(OH)D each 10 years of age. Increasing 25(OH)D levels were significantly associated with decreasing levels of 8-isoprostane levels but neither with LTL nor epigenetic age acceleration. The association of 25(OH)D quartiles with mortality was almost unchanged after adjusting for all aging markers (1.6-fold increased mortality in bottom quartile compared with top quartile). All aging markers were independent mortality predictors and subjects with unfavorable values for 4, 3, 2, and 1 aging marker(s) had 4.3-, 2.9-, 2.2, and 1.4-fold increased mortality, respectively. Conclusions: The 25(OH)D level can be regarded as an aging marker because it is linearly associated with age and an independent mortality predictor. Mechanisms linking vitamin D to healthy aging are unique and can neither be fully explained by aging of the epigenome, loss of telomeres, or antioxidative effects of vitamin D metabolites.


Assuntos
Envelhecimento/sangue , Dinoprosta/análogos & derivados , Epigênese Genética/genética , Epigenômica/métodos , Telômero/metabolismo , Deficiência de Vitamina D/sangue , Vitamina D/análogos & derivados , Idoso , Biomarcadores/sangue , Causas de Morte/tendências , Dinoprosta/sangue , Feminino , Seguimentos , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Vitamina D/sangue , Deficiência de Vitamina D/genética , Deficiência de Vitamina D/mortalidade
6.
In Vivo ; 33(1): 177-182, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30587620

RESUMO

BACKGROUND: The aim of this study was to investigate the association between vitamin D deficiency (<10 mg/ml) and mortality in patients with and without hepatocellular carcinoma (HCC) in a cohort of patients with liver cirrhosis. MATERIALS AND METHODS: A prospective study was conducted among 345 patients with liver cirrhosis. RESULTS: At enrolment, 46 (13.3%) patients had HCC. Severe vitamin D deficiency was associated with mortality (p<0.01). At the survival analysis, alpha-fetoprotein >10 ng/ml (p=0.003), vitamin D deficiency (p<0.001), a Model for End-Stage Liver Disease score ≥15 (p<0.001), Child-Pugh class B and C (versus A) (p<0.001) and the presence of active HCC (p<0.001) were strongly associated with death. At the multivariate Cox regression analysis, only Child-Pugh class B and C (versus A) and vitamin D deficiency were found to be significantly associated with death during the follow-up period (p<0.001 and p=0.006, respectively). CONCLUSION: Vitamin D deficiency is common in patients with HCC, it is associated with active HCC and it negatively affects the overall survival of patients with cirrhosis.


Assuntos
Carcinoma Hepatocelular/mortalidade , Cirrose Hepática/mortalidade , Neoplasias Hepáticas/mortalidade , Deficiência de Vitamina D/mortalidade , Idoso , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/patologia , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Humanos , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática/complicações , Cirrose Hepática/patologia , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Fatores de Risco , Índice de Gravidade de Doença , Vitamina D/metabolismo , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/patologia
7.
BMC Nephrol ; 19(1): 309, 2018 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-30400889

RESUMO

BACKGROUND: Patients with end stage renal disease have a high all-cause and cardiovascular mortality. Secondary hyperparathyroidism and vitamin D deficiency are considered part of the mechanism for the excess mortality observed. We aimed to evaluate the relationship between vitamin D use and all-cause mortality. METHODS: In this retrospective cohort study, we included all incident patients who started hemodialysis in Taiwan between 2001 and 2009. Patients were followed from landmark time, i.e., the 360th day from hemodialysis initiation, through the end of 2010 or death. We evaluated the association between activated vitamin D use or not before landmark time and all-cause mortality using conditional landmark analysis with Cox regression. We used group-based trajectory model to categorize high-dose versus average-dose users to evaluate dose-response relationships. RESULTS: During the median follow-up of 1019 days from landmark time, vitamin D users had a lower crude mortality rate than non-users (8.98 versus 12.93 per 100 person-years). Compared with non-users, vitamin D users was associated with a lower risk of death in multivariate Cox model (HR 0.91 [95% CI, 0.87-0.95]) and after propensity score matching (HR 0.94 [95% CI, 0.90-0.98]). High-dose vitamin D users had a lower risk of death than conventional-dose users, HR 0.75 [95% CI, 0.63-0.89]. The association of vitamin D treatment with reduced mortality did not alter when we re-defined landmark time as the 180th day or repeated analyses in patients who underwent hemodialysis in the hospital setting. CONCLUSIONS: Our findings supported the survival benefits of activated vitamin D among incident hemodialysis patients.


Assuntos
Falência Renal Crônica/mortalidade , Falência Renal Crônica/terapia , Diálise Renal/tendências , Deficiência de Vitamina D/tratamento farmacológico , Deficiência de Vitamina D/mortalidade , Vitamina D/administração & dosagem , Administração Oral , Idoso , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Diálise Renal/efeitos adversos , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Taiwan/epidemiologia , Resultado do Tratamento
8.
Circ Res ; 123(8): 996-1007, 2018 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-30355032

RESUMO

RATIONALE: Bioavailable and free 25-hydroxyvitamin D (25(OH)D) are emerging measurements of vitamin D. Whether serum bioavailable or free 25(OH)D level is associated with mortality in patients with coronary artery disease (CAD) is unknown. OBJECTIVE: Our aim is to determine the potential association between serum total, bioavailable, and free 25(OH)D levels and the risk of mortality among patients with CAD. METHODS AND RESULTS: We measured serum 25(OH) levels in 1387 patients with angiographically confirmed CAD from the Guangdong Coronary Artery Disease Cohort. Serum DBP (vitamin D-binding protein) levels were measured using a polyclonal immunoassay, and serum-free 25(OH)D levels were measured using a 2-step immunoassay. Bioavailable 25(OH)D levels were calculated using a previously validated formula. By the median follow-up time of 6.7 years, 205 patients had died, including 134 deaths from cardiovascular diseases. In multivariate analyses, low serum bioavailable 25(OH)D level was significantly associated with increased risks of mortality, independent of established cardiovascular risk factors, features and treatments of CAD, factors associated with vitamin D and mineral metabolism, and CRP (C-reactive protein). The multivariable-adjusted hazard ratios across quartiles of bioavailable 25(OH)D were 1.79, 1.35, 1.36, and 1.00 for all-cause mortality ( P for trend=0.01) and 2.58, 1.85, 1.73, and 1.00 for cardiovascular mortality ( P for trend=0.001), respectively. Serum-free 25(OH)D level was inversely associated with the risk of mortality, with the extreme-quartile hazard ratios of 1.64 for all-cause mortality ( P for trend=0.024) and 1.97 for cardiovascular mortality ( P for trend=0.013). In contrast, serum total 25(OH)D level was not significantly associated with all-cause mortality or cardiovascular mortality. CONCLUSIONS: Lower serum bioavailable and free 25(OH)D levels rather than total 25(OH)D level are independently associated with an increased risk of all-cause mortality and cardiovascular mortality in a population-based CAD cohort.


Assuntos
Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/mortalidade , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/mortalidade , Vitamina D/análogos & derivados , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Causas de Morte , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Vitamina D/sangue , Deficiência de Vitamina D/diagnóstico
9.
Geriatr Gerontol Int ; 18(12): 1585-1590, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30280463

RESUMO

AIM: Previous studies on the association between low vitamin D level and increased mortality mainly came from high-income countries. The primary objective of the present study was to examine the effect of sex on the association between 25-hydroxyvitamin D2 and D3 and mortality among community-dwelling older people in Thailand. METHODS: A cohort of individuals aged ≥60 years from the Thai 4th National Health Examination Survey carried out in 2008 were followed and linked to a vital registry in 2015. Data regarding comorbid diseases, physical activity and serum vitamin D were obtained at the baseline assessment. Factors associated with all-cause mortality were determined using Cox proportional hazards models. RESULTS: A total of 1268 participants with a median age of 74.0 years (interquartile range 67.0-81.0) were included. The prevalence of vitamin D insufficiency was 24.5% and 43.9% in men and women, respectively. Vitamin D insufficiency was significantly associated with all-cause mortality only among men (adjusted HR 1.77, 95% CI 1.25-2.51), but not women. Analysis of 25-hydroxyvitamin D3 divided into tertiles also showed an association with an adjusted HR of 1.83 (95% CI 1.23-2.72) for the lowest tertile in men. Diabetes was an effect modifier for low serum vitamin D and male sex, with HR 3.34 (95% CI 1.76-6.33, P < 0.001) in diabetic men with vitamin D insufficiency. CONCLUSIONS: Low serum vitamin D is an independent risk factor for increased mortality in community-dwelling Thai older men. Further randomized controlled study to investigate the benefit of vitamin D3 supplementation in older persons, particularly men, is warranted. Geriatr Gerontol Int 2018; 18: 1585-1590.


Assuntos
Doenças Cardiovasculares/epidemiologia , Deficiência de Vitamina D/complicações , Vitamina D/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Doenças Cardiovasculares/etiologia , Causas de Morte/tendências , Estudos Transversais , Feminino , Seguimentos , Humanos , Masculino , Estudos Retrospectivos , Fatores de Risco , Distribuição por Sexo , Fatores Sexuais , Taxa de Sobrevida/tendências , Tailândia/epidemiologia , Fatores de Tempo , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/mortalidade
10.
J Int Med Res ; 46(10): 4246-4257, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30157690

RESUMO

Objective To investigate 25(OH)D3 levels and their relationship to survival in a cohort of acutely ill patients on admission to an intensive care unit. Methods This study enrolled acutely ill patients at admission to an intensive care unit and a group of sex- and age-matched healthy control subjects. The 25(OH)D3 levels were measured using an enzyme immunoassay. C-reactive protein and procalcitonin levels were also measured using immunoassays. Results A total of 50 acutely ill patients and 50 healthy control subjects were enrolled in the study. The mean ± SEM 25(OH)D3 levels were significantly lower in the acutely ill patients compared with the control group (11.74 ± 0.88 ng/ml versus 24.66 ± 1.60 ng/ml, respectively). The 25(OH)D3 levels were not related to survival. An inverse relationship was observed between 25(OH)D3 levels and C-reactive protein levels. A weak inverse relationship was also observed between 25(OH)D3 levels and procalcitonin levels. Conclusions The 25(OH)D3 levels were decreased in acutely ill patients admitted to an intensive care unit compared with healthy control subjects. 25(OH)D3 levels may be inversely related to C-reactive protein and procalcitonin levels.


Assuntos
Calcifediol/sangue , Estado Terminal/mortalidade , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/mortalidade , Doença Aguda , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteína C-Reativa/análise , Calcifediol/deficiência , Calcitonina/sangue , Feminino , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem
11.
Nutrients ; 10(7)2018 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-30011816

RESUMO

Previous meta-analyses have shown an improved survival with higher blood 25-hydroxyvitamin D (25(OH)D) concentrations in patients with colorectal cancer (CRC). However, a number of much larger studies have been published since then. We provide an updated meta-analysis to synthesize current evidence. PubMed and Web of Science databases were systematically searched for eligible studies. The dose-response relationships and pooled hazard ratios for overall and CRC-specific survival comparing the highest versus the lowest categories of blood 25(OH)D concentrations were assessed. Subgroup analyses based on study geographic location, year of publication, sample size, length of follow-up time and stage were conducted to explore potential sources of heterogeneity. Overall, 11 original studies with a total of 7718 CRC patients were included. The dose-response meta-analysis showed an improvement in survival outcomes with increasing blood 25(OH)D concentrations. Pooled hazard ratios (95% confidence intervals) comparing highest versus lowest categories were 0.68 (0.55⁻0.85) and 0.67 (0.57⁻0.78) for overall and CRC-specific survival, respectively. Associations were more prominent among studies conducted in Europe, with larger sample sizes, and including stage I⁻IV patients. This updated meta-analysis reveals robust evidence of an association between higher blood 25(OH)D concentrations and better survival in CRC patients. The potential for enhancing prognosis of CRC patients by vitamin D supplementation should be explored by randomized trials.


Assuntos
Neoplasias Colorretais/sangue , Deficiência de Vitamina D/sangue , Vitamina D/análogos & derivados , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Neoplasias Colorretais/terapia , Progressão da Doença , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Fatores de Proteção , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Vitamina D/sangue , Deficiência de Vitamina D/mortalidade , Deficiência de Vitamina D/terapia
12.
Nutrients ; 10(6)2018 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-29865146

RESUMO

In patients suffering from chronic kidney disease (CKD), the prevalence of cardiovascular disease is much more common than in the general population. The role of vitamin D deficiency had been underestimated until a significant association was found between vitamin D therapy and survival benefit in haemodialysis patients. Vitamin D deficiency is present even in the early stages of chronic kidney disease. The results of experimental studies have revealed the relationship between vitamin D deficiency and impairment of cardiac contractile function, higher cardiac mass and increased myocardial collagen content. Experimental models propose that intermediate end points for the relationship between vitamin D deficiency and higher risk of cardiovascular disease comprise diminished left ventricular hypertrophy (LVH), enhanced left ventricular diastolic function, and decreased frequency of heart failure. Multiple observational studies have demonstrated an association between the use of active vitamin D therapy in patients on dialysis and with CKD and improved survival. However, there are also many studies indicating important adverse effects of such treatment. Therefore, large randomized trials are required to analyze whether supplementation of vitamin D may affect outcomes and whether it is safe to be used in CKD patients.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Suplementos Nutricionais , Diálise Renal , Insuficiência Renal Crônica/terapia , Deficiência de Vitamina D/fisiopatologia , Vitamina D/uso terapêutico , Animais , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/fisiopatologia , Sistema Cardiovascular/metabolismo , Sistema Cardiovascular/patologia , Sistema Cardiovascular/fisiopatologia , Suplementos Nutricionais/efeitos adversos , Humanos , Diálise Renal/efeitos adversos , Diálise Renal/mortalidade , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/mortalidade , Insuficiência Renal Crônica/fisiopatologia , Fatores de Risco , Vitamina D/efeitos adversos , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/diagnóstico por imagem , Deficiência de Vitamina D/mortalidade
13.
Biosci Rep ; 38(2)2018 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-29437901

RESUMO

To assess the hypothesis that vitamin D, reflected by 25-hydroxyvitamin D (25(OH) D) would be associated with higher risk of poor functional outcomes amongst nondiabetic stroke patients. The present study was conducted in Nanchang, China. Serum concentration of 25(OH) D and National Institutes of Health Stroke Scale (NIHSS) were measured at the time of admission. Functional outcome was measured by modified Rankin scale (mRS) at 1 year after admission. Multivariate analyses were performed using logistic regression models. The cut point of 25(OH) D level for vitamin D deficiency was 20 ng/ml. In the present study, 266 nondiabetic subjects with stroke were included; 149 out of the 266 patients were defined as vitamin D deficiency (56%). The poor outcome distribution across the 25(OH) D quartiles ranged between 64% (first quartile) and 13% (fourth quartile). In those 149 patients with vitamin D deficiency, 75 patients were defined as poor functional outcomes, giving a prevalence rate of 50% (95% confidence interval (CI): 42-58%). In multivariate analysis models, for vitamin D deficiency, the adjusted risk of poor functional outcomes and mortality increased by 220% (odds ratio (OR): 3.2; 95% CI: 1.7-4.2, P<0.001) and 290% (OR: 3.9; 95% CI: 2.1-5.8, P<0.001), respectively. Vitamin D deficiency is associated with an increased risk of poor functional outcome events in Chinese nondiabetic stroke individuals.


Assuntos
Isquemia Encefálica/sangue , Isquemia Encefálica/mortalidade , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/mortalidade , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/mortalidade , Idoso , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida
14.
Nutrients ; 10(1)2018 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-29315215

RESUMO

Some observational studies suggest an inverse association between circulating 25-hydroxyvitamin D (25OHD) and cancer incidence and mortality. We conducted a Mendelian randomization analysis of the relationship between a vitamin D genetic risk score (GRS, range 0-10), comprised of five single nucleotide polymorphisms (SNPs) of vitamin D status in the DHCR7, CYP2R1 and GC genes and cancer risk among women. Analysis was performed in the Women's Genome Health Study (WGHS), including 23,294 women of European ancestry who were cancer-free at baseline and followed for 20 years for incident cancer. In a subgroup of 1782 WGHS participants with 25OHD measures at baseline, the GRS was associated with circulating 25OHD mean (SD) = 67.8 (26.1) nmol/L, 56.9 (18.7) nmol/L in the lowest versus 73.2 (27.9) nmol/L in the highest quintile of the GRS (p trend < 0.0001 across quintiles). However, in age-adjusted Cox proportional hazards models, higher GRS (reflecting higher 25OHD levels) was not associated (cases; Hazard Ratio (HR) (95% Confidence Interval (CI)), p-value) with incident total cancer: (n = 3985; 1.01 (1.00-1.03), p = 0.17), breast (n = 1560; 1.02 (0.99-1.05), p = 0.21), colorectal (n = 329; 1.06 (1.00-1.13), p = 0.07), lung (n = 330; 1.00 (0.94-1.06), p = 0.89) or total cancer death (n = 770; 1.00 (0.96-1.04), p = 0.90). Results were similar in fully-adjusted models. A GRS for higher circulating 25OHD was not associated with cancer incidence or mortality.


Assuntos
Colestanotriol 26-Mono-Oxigenase/genética , Família 2 do Citocromo P450/genética , Neoplasias/epidemiologia , Neoplasias/genética , Oxirredutases atuantes sobre Doadores de Grupo CH-CH/genética , Polimorfismo de Nucleotídeo Único , Deficiência de Vitamina D/epidemiologia , Deficiência de Vitamina D/genética , Proteína de Ligação a Vitamina D/genética , Vitamina D/análogos & derivados , Biomarcadores/sangue , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , Incidência , Modelos Lineares , Análise da Randomização Mendeliana , Pessoa de Meia-Idade , Neoplasias/sangue , Neoplasias/mortalidade , Razão de Chances , Fenótipo , Modelos de Riscos Proporcionais , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Estados Unidos/epidemiologia , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/mortalidade
15.
Pediatr Blood Cancer ; 65(2)2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28960811

RESUMO

BACKGROUND: Pediatric patients undergoing hematopoietic stem cell transplantation (HSCT) are frequently diagnosed with vitamin D deficiency, which may impact outcomes. OBJECTIVES: To estimate the prevalence of vitamin D deficiency and examine its association with short-term survival in pediatric HSCT patients. METHODS: Patients undergoing HSCT at Phoenix Children's Hospital were retrospectively identified. Routine serum 25-hydroxyvitamin D measurements were described prior to transplant and at 100 days and 1-year post-HSCT. Associations of pre-HSCT vitamin D groups (i.e., normal ≥30 ng/ml, insufficient 20-29 ng/ml, and deficient <30 ng/ml) with demographics, clinical factors, and outcomes were examined using nonparametric tests and Cox proportional hazards analyses. RESULTS: Among 72 study subjects, the median vitamin D pre-HSCT was 26 ng/ml (range: 19-34 ng/ml). Levels were insufficient and deficient in 25 (35%) and 20 (28%) patients, respectively, with only two (3%) patients on supplemental therapy pre-HSCT. Despite supplemental therapy provided to 46 (74%) subjects, insufficient/deficient rates did not significantly change between pre-HSCT and 100 days post-HSCT, but mean vitamin D levels significantly increased by 1-year post-HSCT (P = 0.01).Vitamin D pre-HSCT was not associated with the development of acute or chronic graft-versus-host disease (GVHD) or delayed engraftment. Overall 1-year survival was significantly lower for patients with deficient (65%) compared to normal (93%) pre-HSCT vitamin D (P = 0.001). CONCLUSION: Suboptimal vitamin D levels are common in pediatric patients scheduled to receive HSCT and are associated with lower overall 1-year survival. Further study is warranted to delineate the mechanisms underlying the role of vitamin D in successful HSCT.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/mortalidade , Vitamina D/análogos & derivados , Adolescente , Adulto , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Lactente , Masculino , Neoplasias/sangue , Neoplasias/mortalidade , Neoplasias/terapia , Taxa de Sobrevida , Fatores de Tempo , Vitamina D/sangue , Deficiência de Vitamina D/terapia
16.
J Neurosurg ; 128(6): 1635-1641, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-28799870

RESUMO

OBJECTIVE Vitamin D deficiency has been associated with a variety of negative outcomes in critically ill patients, but little focused study on the effects of hypovitaminosis D has been performed in the neurocritical care population. In this study, the authors examined the effect of vitamin D deficiency on 3-month outcomes after discharge from a neurocritical care unit (NCCU). METHODS The authors prospectively analyzed 25-hydroxy vitamin D levels in patients admitted to the NCCU of a quaternary care center over a 6-month period. Glasgow Outcome Scale (GOS) scores were used to evaluate their 3-month outcome, and univariate and multivariate logistic regression was used to evaluate the effects of vitamin D deficiency. RESULTS Four hundred ninety-seven patients met the inclusion criteria. In the binomial logistic regression model, patients without vitamin D deficiency (> 20 ng/dl) were significantly more likely to have a 3-month GOS score of 4 or 5 than those who were vitamin D deficient (OR 1.768 [95% CI 1.095-2.852]). Patients with a higher Simplified Acute Physiology Score (SAPS II) (OR 0.925 [95% CI 0.910-0.940]) and those admitted for stroke (OR 0.409 [95% CI 0.209-0.803]) or those with an "other" diagnosis (OR 0.409 [95% CI 0.217-0.772]) were significantly more likely to have a 3-month GOS score of 3 or less. CONCLUSIONS Vitamin D deficiency is associated with worse 3-month postdischarge GOS scores in patients admitted to an NCCU. Additional study is needed to determine the role of vitamin D supplementation in the NCCU population.


Assuntos
Cuidados Críticos , Escala de Resultado de Glasgow , Estado Nutricional , Deficiência de Vitamina D/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Lesões Encefálicas Traumáticas/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores de Risco , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/mortalidade , Acidente Vascular Cerebral/terapia , Vitamina D/análogos & derivados , Vitamina D/sangue , Deficiência de Vitamina D/mortalidade
17.
J Steroid Biochem Mol Biol ; 175: 60-81, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-27662817

RESUMO

The aim of this study is to determine and critically evaluate the plausible relationships of vitamin D with extra-skeletal tissues in humans. Severe vitamin D deficiency results in rickets in children and osteomalacia in adults; these beneficial effects in the musculoskeletal system and certain physiological functions are well understood. Nevertheless, mounting reports support additional beneficial effects of vitamin D, outside the musculoskeletal system. This review explores the recent advances in knowledge about the non-skeletal effects of vitamin D. Peer-reviewed papers were extracted from research databases using key words, to assess correlations between vitamin D and extra-skeletal diseases and conditions. As per the guidelines of the Preferred Reporting Items for Systematic Reviews (PRISMA); general interpretations of results are included; taking into consideration the broader evidence and implications. This review summarizes current knowledge of the effects of vitamin D status on extra-skeletal tissues with special attention given to relationships between vitamin D status and various diseases commonly affecting adults; the effects of intervention with vitamin D and exposure to sunlight. Evidence suggests that vitamin D facilitates the regulation of blood pressure; and cardiac; endothelial; and smooth muscle cell functions; playing an important role in cardiovascular protection. In addition; 1,25(OH)2D improves immunity; subdues inflammation; and reduces the incidence and severity of common cancers; autoimmune diseases and infectious diseases. Almost all adequately powered; epidemiological and biological studies that use; adequate doses of vitamin D supplementation in D-deficient populations have reported favorable outcomes. These studies have concluded that optimizing 25(OH)D status improves the functionality of bodily systems; reduces comorbidities; improves the quality of life; and increases survival. Although accumulating evidence supports biological associations of vitamin D sufficiency with improved physical and mental functions; no definitive evidence exists from well-designed; statistically powered; randomized controlled clinical trials. Nevertheless, most studies point to significant protective effects of vitamin D in humans when the minimum 25(OH)D serum level exceeds 30ng/mL and is maintained throughout the year.


Assuntos
Doenças Autoimunes/sangue , Doenças Cardiovasculares/sangue , Diabetes Mellitus/sangue , Doenças Neurodegenerativas/sangue , Deficiência de Vitamina D/sangue , Vitamina D/análogos & derivados , Doenças Autoimunes/complicações , Doenças Autoimunes/etnologia , Doenças Autoimunes/mortalidade , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/etnologia , Doenças Cardiovasculares/mortalidade , Grupos de Populações Continentais , Complicações do Diabetes , Diabetes Mellitus/etnologia , Diabetes Mellitus/mortalidade , Humanos , Incidência , Doenças Neurodegenerativas/complicações , Doenças Neurodegenerativas/etnologia , Doenças Neurodegenerativas/mortalidade , Osteoporose/sangue , Osteoporose/complicações , Osteoporose/etnologia , Osteoporose/mortalidade , Sarcopenia/sangue , Sarcopenia/complicações , Sarcopenia/etnologia , Sarcopenia/mortalidade , Análise de Sobrevida , Vitamina D/sangue , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/etnologia , Deficiência de Vitamina D/mortalidade
18.
J Steroid Biochem Mol Biol ; 175: 29-43, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28027913

RESUMO

Vitamin D regulates blood pressure, cardiac functions, and endothelial and smooth muscle cell functions, thus, playing an important role in cardiovascular health. Observational studies report associations between vitamin D deficiency with hypertension and cardiovascular-related deaths. Peer-reviewed papers were examined in several research databases as per the guidelines of the Preferred Reporting Items for Systematic Reviews, using key words that address the relationship between vitamin D and cardiovascular disease. Correlations and interpretations were made considering the risks-benefits, broader evidence, and implications. This review analyzed current knowledge regarding the effects of vitamin D on the cardiovascular system. 1,25(OH)2D and related epigenetic modifications subdue cellular inflammation, improve overall endothelial functions, reduce age-related systolic hypertension and vascular rigidity, and attenuate the actions of the renin-angiotensin-aldosterone system. Most observational and ecological studies support 25(OH)vitamin D having protective effects on the cardiovascular system. However, the association of vitamin D deficiency with cardiovascular diseases is based primarily on observational and ecological studies and thus, is a matter of controversy. Adequately powered, randomized controlled clinical trial data are not available to confirm these associations. Thus, to test the hypothesis that correction of vitamin D deficiency protects the cardiovascular system, well-designed, statistically powered, longer-term clinical trials are needed in persons with vitamin D deficiency. Nevertheless, the available data support that adequate vitamin D supplementation and/or sensible sunlight exposure to achieve optimal vitamin D status are important in the prevention of cardiovascular disease and other chronic diseases.


Assuntos
Doenças Cardiovasculares/metabolismo , Suplementos Nutricionais , Calcificação Vascular/metabolismo , Deficiência de Vitamina D/metabolismo , Vitamina D/administração & dosagem , Cálcio/metabolismo , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/dietoterapia , Doenças Cardiovasculares/mortalidade , Ensaios Clínicos como Assunto , Humanos , Sistema Renina-Angiotensina/efeitos dos fármacos , Fatores de Risco , Análise de Sobrevida , Raios Ultravioleta , Calcificação Vascular/complicações , Calcificação Vascular/dietoterapia , Calcificação Vascular/genética , Vitamina D/efeitos adversos , Vitamina D/análogos & derivados , Vitamina D/sangue , Vitamina D/metabolismo , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/dietoterapia , Deficiência de Vitamina D/mortalidade
19.
Nutr Metab Cardiovasc Dis ; 27(12): 1143-1151, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29170060

RESUMO

BACKGROUND AND AIMS: The impact of vitamin D concentrations on subsequent cardiovascular disease (CVD) and overall mortality has been generally examined for periods under two decades. The magnitude of the association may depend on follow-up length. We aimed to investigate the relationship between baseline vitamin D and risk of total CVD, stroke and all-cause mortality over three decades of follow-up. Secondly, we aimed to assess how follow-up affects the associations. METHODS AND RESULTS: Concentrations of 25-hydroxyvitamin D (25D) were measured in a population-based sample of 1227 middle-aged women using serum collected at baseline and categorized into low (lowest 25D quartile) vs high 25D status (upper three 25D quartiles). Hazard ratio (HR) of the endpoints was estimated for low 25D. The impact of follow-up was examined in intermediary analyses where follow-up was interrupted up to four times, each time decreasing it by five years. There were 596 cardiovascular events and 635 participants died. During the first 17 years, the low 25D group experienced a 29% higher CVD risk and 3.3-fold higher stroke risk after accounting for confounders. Longer follow-up diminished significantly these risks and 25D status had no contribution at 32 years. For mortality, the decline over time was less dramatic, with HR = 1.96 (1.25; 3.08) at 17 years and HR = 1.42 (1.17; 1.72) at 37 years. CONCLUSION: Low 25D status increased the risk for all endpoints, but a lengthy follow-up diminished these risks towards the null. The impact of follow-up depends on the outcome. Future studies of 25D and disease should use repeated 25D assessments.


Assuntos
Doenças Cardiovasculares/mortalidade , Deficiência de Vitamina D/mortalidade , Saúde da Mulher , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Doenças Cardiovasculares/diagnóstico , Causas de Morte , Feminino , Seguimentos , Nível de Saúde , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Medição de Risco , Fatores de Risco , Fatores Sexuais , Suécia/epidemiologia , Fatores de Tempo , Vitamina D/análogos & derivados , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/diagnóstico
20.
Cochrane Database Syst Rev ; 11: CD011564, 2017 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-29099543

RESUMO

BACKGROUND: Vitamin D deficiency is often reported in people with chronic liver diseases. Therefore, improving vitamin D status could have a beneficial effect on people with chronic liver diseases. OBJECTIVES: To assess the beneficial and harmful effects of vitamin D supplementation in people with chronic liver diseases. SEARCH METHODS: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Science Citation Index Expanded, and Conference Proceedings Citation Index - Science. We also searched databases of ongoing trials and the World Health Organization International Clinical Trials Registry Platform. We scanned bibliographies of relevant publications and asked experts and pharmaceutical companies for additional trials. All searches were up to January 2017. SELECTION CRITERIA: Randomised clinical trials that compared vitamin D at any dose, duration, and route of administration versus placebo or no intervention in adults with chronic liver diseases. Vitamin D could have been administered as supplemental vitamin D (vitamin D3 (cholecalciferol) or vitamin D2 (ergocalciferol)), or an active form of vitamin D (1α-hydroxyvitamin D (alfacalcidol), 25-hydroxyvitamin D (calcidiol), or 1,25-dihydroxyvitamin D (calcitriol)). DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by The Cochrane Collaboration. We contacted authors of the trials to ask for missing information. We conducted random-effects and fixed-effect meta-analyses. For dichotomous outcomes, we calculated risk ratios (RRs), and for continuous outcomes, we calculated mean differences (MD), both with 95% confidence intervals (CI) and Trial Sequential Analyses-adjusted CIs. We calculated Peto odds ratio (OR) for rare events. We considered risk of bias in domains to assess the risk of systematic errors. We conducted Trial Sequential Analyses to control the risk of random errors. We assessed the quality of the evidence with GRADE. MAIN RESULTS: We included 15 randomised clinical trials with 1034 participants randomised. All trials had a parallel group design. Nine trials were conducted in high-income countries and six trials in middle-income countries. All trials were at high risk of bias. Six trials included participants with chronic hepatitis C, four trials included participants with liver cirrhosis, four trials included participants with non-alcoholic fatty liver disease, and one trial included liver transplant recipients. All included trials reported the baseline vitamin D status of participants. Participants in six trials had baseline 25-hydroxyvitamin D levels at or above vitamin D adequacy (20 ng/mL), while participants in the remaining nine trials were vitamin D insufficient (less than 20 ng/mL). All trials administered vitamin D orally. Mean duration of vitamin D supplementation was 0.5 years and follow-up was 0.6 years. Eleven trials (831 participants; 40% women; mean age 52 years) tested vitamin D3, one trial (18 men; mean age 61 years) with three intervention groups tested vitamin D2 and 25-dihydroxyvitamin D in separate groups, and three trials (185 participants; 55% women; mean age 55 years) tested 1,25-dihydroxyvitamin D. Seven trials used placebo, and eight trials used no intervention in the control group.The effect of vitamin D on all-cause mortality at the end of follow-up is uncertain because the results were imprecise (Peto OR 0.70, 95% CI 0.09 to 5.38; I2 = 32%; 15 trials; 1034 participants; very low quality evidence). Trial Sequential Analysis on all-cause mortality was performed based on a mortality rate in the control group of 10%, a relative risk reduction of 28% in the experimental intervention group, a type I error of 2.5%, and type II error of 10% (90% power). There was no diversity. The required information size was 6396 participants. The cumulative Z-curve did not cross the trial sequential monitoring boundary for benefit or harm after the 15th trial, and the Trial Sequential Analyses-adjusted CI was 0.00 to 2534.The effect of vitamin D on liver-related mortality (RR 1.62, 95% CI 0.08 to 34.66; 1 trial; 18 participants) and on serious adverse events such as hypercalcaemia (RR 5.00, 95% CI 0.25 to 100.8; 1 trial; 76 participants), myocardial infarction (RR 0.75, 95% CI 0.08 to 6.81; 2 trials; 86 participants), and thyroiditis (RR 0.33 95% CI 0.01 to 7.91; 1 trial; 68 participants) is uncertain because the results were imprecise. The evidence on all these outcomes is of very low quality. The effect of vitamin D3 on non-serious adverse events such as glossitis (RR 3.70, 95% CI 0.16 to 87.6; 1 trial; 65 participants; very low quality of evidence) is uncertain because the result was imprecise.Due to few data, we did not conduct Trial Sequential Analysis on liver-related mortality, and serious and non-serious adverse events.We found no data on liver-related morbidity and health-related quality of life in the randomised trials included in this review. AUTHORS' CONCLUSIONS: We are uncertain as to whether vitamin D supplements in the form of vitamin D3, vitamin D2, 1,25-dihydroxyvitamin D, or 25-dihydroxyvitamin D have important effect on all-cause mortality, liver-related mortality, or on serious or non-serious adverse events because the results were imprecise. There is no evidence on the effect of vitamin D supplementation on liver-related morbidity and health-related quality of life. Our conclusions are based on few trials with an insufficient number of participants and on lack of data on clinically important outcomes. In addition, the analysed trials are at high risk of bias with significant intertrial heterogeneity. The overall quality of evidence is very low.


Assuntos
Hepatopatias/complicações , Deficiência de Vitamina D/terapia , Vitamina D/administração & dosagem , Vitaminas/administração & dosagem , Administração Oral , Calcitriol/administração & dosagem , Causas de Morte , Colecalciferol/administração & dosagem , Doença Crônica , Ergocalciferóis/administração & dosagem , Feminino , Hepatite C Crônica/sangue , Hepatite C Crônica/complicações , Humanos , Hidroxicolecalciferóis/administração & dosagem , Cirrose Hepática/sangue , Cirrose Hepática/complicações , Hepatopatias/sangue , Hepatopatias/mortalidade , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/complicações , Ensaios Clínicos Controlados Aleatórios como Assunto , Vitamina D/análogos & derivados , Deficiência de Vitamina D/mortalidade
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