Temporal Relationship between Vitamin D Status and Parathyroid Hormone in the United States

Background

Interpretation of parathyroid hormone (iPTH) requires knowledge of vitamin D status that is influenced by season.

Objective

Characterize the temporal relationship between 25-hydroxyvitamin D₃ levels [25(OH)D₃] and intact iPTH for several seasons, by gender and latitude in the U.S. and relate 25-hydrovitamin D₂ [25(OH)D₂] levels with PTH levels and total 25(OH)D levels.

Method

We retrospectively determined population weekly-mean concentrations of unpaired [25(OH)D₂ and 25(OH)D₃] and iPTH using 3.8 million laboratory results of adults. The 25(OH)D₃ and iPTH distributions were normalized and the means fit with a sinusoidal function for both gender and latitudes: North >40, Central 32–40 and South <32 degrees. We analyzed PTH and total 25(OH)D separately in samples with detectable 25(OH)D₂ (≥4 ng/mL).

Findings

Seasonal variation was observed for all genders and latitudes. 25(OH)D₃ peaks occurred in September and troughs in March. iPTH levels showed an inverted pattern of peaks and troughs relative to 25(OH)D₃, with a delay of 4 weeks. Vitamin D deficiency and insufficiency was common (33% <20 ng/mL; 60% <30 ng/mL) as was elevated iPTH levels (33%>65 pg/mL). The percentage of patients deficient in 25(OH)D₃ seasonally varied from 21% to 48% and the percentage with elevated iPTH reciprocally varied from 28% to 38%. Patients with detectable 25(OH)D₂ had higher PTH levels and 57% of the samples with a total 25(OH)D > 50 ng/mL had detectable 25(OH)D₂.

Interpretation

25(OH)D₃ and iPTH levels vary in a sinusoidal pattern throughout the year, even in vitamin D₂ treated patients; 25(OH)D₃, being higher in the summer and lower in the winter months, with iPTH showing the reverse pattern. A large percentage of the tested population showed vitamin D deficiency and secondary hyperparathyroidism. These observations held across three latitudinal regions, both genders, multiple-years, and in the presence or absence of detectable 25(OH)D₂, and thus are applicable for patient care.     

Vitamin D Levels Decline with Rising Number of Cardiometabolic Risk Factors in Healthy Adults: Association with Adipokines,Inflammation, Oxidative Stress and Advanced Glycation Markers

Introduction

Hypovitaminosis D associates with obesity, insulin resistance, hypertension, and dyslipoproteinemia. We asked whether the presence of multiple cardiometabolic risk factors, and which particular combination, exerts additive negative effects on 25(OH)D₃ levels; and whether 25(OH)D₃ levels associate with markers of inflammation and oxidative stress.

Subjects and Methods

In non-diabetic medication-free adults central obesity (waist-to-height ratio > 0.5); elevated blood pressure (systolic BP≥130 mm Hg and/or diastolic BP ≥85 mm Hg); increased atherogenic risk (log(TAG/HDL) ≥ 0.11); and insulin resistance (QUICKI < 0.322) were considered as cardiometabolic risk factors. 25(OH)D₃ status was classified as deficiency (25(OH)D₃ ≤20 ng/ml); insufficiency (levels between 20-to-30 ng/ml), or as satisfactory (>30 ng/ml). Plasma adipokines, inflammatory and oxidative stress markers, advanced glycation end-products, and their soluble receptor were determined.

Results

162 subjects were cardiometabolic risk factors-free, 162 presented increased (i.e. 1 or 2), and 87 high number (i.e. 3 or 4) of cardiometabolic risk factors. Mean 25(OH)D₃ decreased with rising number of manifested risk factors (36 ± 14 ng/ml, 33 ± 14 ng/ml, and 31 ± 15 ng/ml, respectively; p_ANOVA: 0.010), while prevalence of hypovitaminosis D did not differ significantly. Elevated blood pressure and insulin resistance appeared as significant determinants of hypovitaminosis D. Subjects presenting these risk factors concurrently displayed the lowest 25(OH)D₃ levels (29 ± 15 ng/ml). Plasma adipokines, inflammatory and oxidative stress markers, advanced glycation end-products, and their soluble receptor generally differed significantly between the groups, but only advanced oxidation protein products and advanced glycation end-products associated fluorescence of plasma showed significant independent association with 25(OH)D₃ levels.

Conclusion

In apparently healthy adults increasing number of cardiometabolic risk factors associates with poorer 25(OH)D₃ status, while the association between 25(OH)D₃ status and inflammatory or oxidative stress markers remains equivocal.     

25-Hydroxyvitamin D3 Deficiency Independently Predicts Cognitive Impairment in Patients with Systemic Lupus Erythematosus

Objectives

Cognitive dysfunction has been reported in 20–80% of SLE patients. Converging evidence has indicated the importance of vitamin D as a neuroimmunomodulator for cognitive function. In this study, we evaluated the relationship between vitamin D and cognitive dysfunction.

Methods

Consecutive age- and gender-matched SLE patients and healthy controls (HCs) were administered Automated Neuropsychological Assessment Metrics in this cross-sectional study. The primary outcome was the total throughput score (TTS). Anxiety and depression were measured using the Hospital Anxiety and Depression Scale (HADS). Levels of 25-hydroxyvitamin D [25(OH)D₃ and total 25(OH)D] were measured using Liquid Chromatography-Tandem Mass Spectrometry.

Results

In total, 61 SLE patients and 61 HCs were studied. SLE patients scored significantly lower than HCs in the TTS (p = 0.004). There were no statistically significant differences in 25(OH)D₃ levels, total 25(OH)D levels and total 25(OH)D deficiency between SLE patients and HCs. However, more SLE patients had 25(OH)D₃ deficiency compared to HCs [12 (19.7%) versus 2 (3.3%), p = 0.003]. Deficiency of 25(OH)D₃ (β = -63.667, SE = 27.456, p = 0.025), but not other vitamin D variables, independently predicted worse TTS after adjusting for age, education, gender, ethnicity, HADS-Total, duration of SLE, SELENA-SLEDAI, SLICC/ACR Damage Index and cumulative steroid dose in SLE patients. Age (β = -4.261, SE = 0.866, p < 0.001) was the only predictor of TTS after adjusting for education, gender, ethnicity, HADS-Total, vitamin D levels or status in HCs.

Conclusions

Deficiency of 25(OH)D₃, a potentially modifiable risk factor, independently predicted cognitive impairment in SLE patients.     

Inverse Association of Serum Vitamin D in Relation to Carotid Intima-Media Thickness in Chinese Postmenopausal Women

Objective

This study aimed to investigate the relationship between serum vitamin D level and carotid intima-media thickness (C-IMT) in Chinese postmenopausal women.

Methods

Nine hundred and twenty six Chinese postmenopausal women without carotid artery plaque or history of cardiovascular disease were selected for analysis. Measurements of serum 25 hydroxyvitamin D₃ (25(OH)D₃) concentration and C-IMT were made by electrochemiluminescence immunoassay and B-mode ultrasound, respectively. Trend analysis was conducted according to tertiles of C-IMT.

Results

The median serum 25(OH)D₃ level was 11.03 ng/mL, with an interquartile range of 8.22–14.70. A decreasing trend of serum 25(OH)D₃ level was accompanied by increased C-IMT tertiles (P for trend = 0.001). Correlation analysis found an inverse relationship between serum 25(OH)D₃ level and C-IMT (r = –0.113, P = 0.001). After adjustment for confounding factors, multiple regression analysis showed that serum 25(OH)D₃ level independently and negatively associated with C-IMT (Standard β = –0.112, P < 0.001). Moreover, the inverse correlation of serum 25(OH)D₃ with C-IMT was also found in a subgroup of women with normal glucose tolerance, blood pressure and body mass index, and without undergoing lipid-lowering therapy (standard β = –0.140, P = 0.018).

Conclusions

Serum 25(OH)D₃ level was inversely correlated with C-IMT in Chinese postmenopausal women.     

The association of 25-hydroxyvitamin D3 and D2 with behavioural problems in childhood

Background

Higher serum concentrations of 25-hydroxyvitamin D (25(OH)D), an indicator of vitamin D synthesis and intake, have been associated with better mental health and cognitive function. Concentrations of 1,25-dihydroxyvitamin D₃ (the active vitamin D₃ metabolite) have been associated with openness and extrovert behaviour, but 25(OH)D concentrations have not been associated with behavioural problems in humans.

Methods

We investigated the prospective association between the different forms of 25(OH)D - 25(OH)D₃ and 25(OH)D₂– and childhood behavioural problems in Avon Longitudinal Study of Parents and Children (ALSPAC). Serum 25(OH)D₃ and 25(OH)D₂ concentrations were assessed at mean age 9.9 years. Incident behavioural problems were assessed with Strengths and Difficulties Questionnaire (SDQ; emotional symptoms, conduct problems, hyperactivity-inattention problems, peer relationship problems and pro-social behaviour subscales and total difficulties score) at mean age 11.7. Sample sizes varied between 2413-2666 depending on the outcome.

Results

Higher 25(OH)D₃ concentrations were weakly associated with lower risk of prosocial problems (fully adjusted odds ratio: OR (95% confidence interval: CI) 0.85 (0.74, 0.98)). Serum 25(OH)D₃ or 25(OH)D₂ concentrations were not associated with other subscales of SDQ or total difficulties score after adjusting for concfounders and other measured analytes related to vitamin D.

Conclusions

Our findings do not support the hypothesis that 25-hydroxyvitamin D status in childhood has important influences on behavioural traits in humans.     

Oral Supplementation with Cholecalciferol 800 IU Ameliorates Albuminuria in Chinese Type 2 Diabetic Patients with Nephropathy

Background

Low vitamin D levels can be associated with albuminuria, and vitamin D analogs are effective anti-proteinuric agents. The aim of this study was to investigate differences in vitamin D levels between those with micro- and those with macroalbuminuria, and to determine whether low dose cholecalciferol increases vitamin D levels and ameliorates albuminuria.

Methods

Two studies were performed in which 25-OH vitamin D₃ (25(OH)D₃) concentrations were determined by electrochemiluminescence immunoassay: 1) a cross-sectional study of patients with type 2 diabetes mellitus (T2DM) (n = 481) and healthy controls (n = 78); and 2) a longitudinal study of T2DM patients with albuminuria treated with conventional doses, 800 IU, of cholecalciferol for 6 months (n = 22), and a control group (n = 24).

Results

1) Cross-sectional study: Compared to controls and T2DM patients with normoalbuminuria, serum 25(OH)D₃ concentrations were significantly lower in patients with macro-albuminuria, but not in those with micro-albuminuria. Serum 25(OH)D₃ levels were independently correlated with microalbuminuria. 2) Longitudinal study: Cholecalciferol significantly decreased microalbuminuria in the early stages of treatment, in conjunction with an increase in serum 25(OH)D₃ levels.

Conclusions

Low vitamin D levels are common in type 2 diabetic patients with albuminuria, particularly in patients with macroalbuminuria, but not in those with microalbuminuria. Conventional doses of cholecalciferol may have antiproteinuric effects on Chinese type 2 diabetic patients with nephropathy.     

Serum 25-hydroxyvitamin d(3) and d(2) and non-clinical psychotic experiences in childhood

Objective

Non-clinical psychotic experiences are common and distressing. It has been hypothesized that early life vitamin D deficiency may be a risk factor for psychosis-related outcomes, but it is not known if circulating concentrations of 25-hydroxyvitamin D (25(OH)D) during childhood are associated with psychosis-related outcomes or whether the two different forms of 25(OH)D, (25(OH)D₃ and 25(OH)D₂, have similar associations with psychosis-related outcomes.

Methods

We investigated the association between serum 25(OH)D₃ and 25(OH)D₂ concentrations and psychotic experiences in a prospective birth cohort study. Serum 25(OH)D₃ and 25(OH)D₂ concentrations were measured at mean age 9.8 years and psychotic experiences assessed at mean age 12.8 years by a psychologist (N = 3182).

Results

Higher 25(OH)D₃ concentrations were associated with lower risk of definite psychotic experiences (adjusted odds ratio: OR (95% confidence interval: CI) 0.85 (0.75–0.95)). Higher concentrations of 25(OH)D₂ were associated with higher risk of suspected and definite psychotic experiences (adjusted odds ratio: OR (95% confidence interval: CI) 1.26 (1.11, 1.43)). Higher 25(OD)D₂ concentrations were also weakly associated with definite psychotic experiences (adjusted OR (95% CI) 1.17 (0.96, 1.43), though with wide confidence intervals including the null value.

Conclusions

Our findings of an inverse association of 25(OH)D₃ with definite psychotic experiences is consistent with the hypothesis that vitamin D may protect against psychosis-related outcomes.     

Vitamin D,Vitamin D Binding Protein,and Longitudinal Outcomes in COPD

Background

Associations between Vitamin D₃ [25(OH)D], vitamin D binding protein (VDBP) and chronic obstructive pulmonary disease (COPD) are previously reported. We aimed to further investigate these associations on longitudinal outcomes.

Methods

426 COPD patients from western Norway, GOLD stage II-IV, aged 40–76, were followed every six-month from 2006 through 2009 with spirometry, bioelectrical impedance measurements and registration of exacerbation frequency. Serum 25(OH)D and VDBP levels were determined at study-entry by high-performance liquid chromatography coupled with mass spectrometry and enzyme immunoassays respectively. Yearly change in lung function and body composition was assessed by generalized estimating equations (GEE), yearly exacerbation rate by negative binomial regression models, and 5 years all-cause mortality by Cox proportional-hazard regression.

Results

1/3 of the patients had vitamin D deficiency (<20ng/mL) and a greater decline in both FEV1 and FVC, compared to patients with normal levels; for FEV1 this difference only reached statistical significance in the 28 patients with the lowest levels (<10ng/mL, p = 0.01). Neither 25(OH)D nor VDBP levels predicted exacerbation rate, change in fat free mass index or risk of death.

Conclusion

Severe vitamin D deficiency may affect decline in lung function parameters in COPD. Neither 25(OH)D nor VDBP levels did otherwise predict markers of disease progression.     

Vitamin D Metabolites and Their Association with Calcium,Phosphorus, and PTH Concentrations,Severity of Illness,and Mortality in Hospitalized Equine Neonates

Background

Hypocalcemia is a frequent abnormality that has been associated with disease severity and outcome in hospitalized foals. However, the pathogenesis of equine neonatal hypocalcemia is poorly understood. Hypovitaminosis D in critically ill people has been linked to hypocalcemia and mortality; however, information on vitamin D metabolites and their association with clinical findings and outcome in critically ill foals is lacking. The goal of this study was to determine the prevalence of vitamin D deficiency (hypovitaminosis D) and its association with serum calcium, phosphorus, and parathyroid hormone (PTH) concentrations, disease severity, and mortality in hospitalized newborn foals.

Methods and Results

One hundred newborn foals ≤72 hours old divided into hospitalized (n = 83; 59 septic, 24 sick non-septic [SNS]) and healthy (n = 17) groups were included. Blood samples were collected on admission to measure serum 25-hydroxyvitamin D₃ [25(OH)D₃], 1,25-dihydroxyvitamin D₃ [1,25(OH) ₂D₃], and PTH concentrations. Data were analyzed by nonparametric methods and univariate logistic regression. The prevalence of hypovitaminosis D [defined as 25(OH)D₃ <9.51 ng/mL] was 63% for hospitalized, 64% for septic, and 63% for SNS foals. Serum 25(OH)D₃ and 1,25(OH) ₂D₃ concentrations were significantly lower in septic and SNS compared to healthy foals (P<0.0001; P = 0.037). Septic foals had significantly lower calcium and higher phosphorus and PTH concentrations than healthy and SNS foals (P<0.05). In hospitalized and septic foals, low 1,25(OH)₂D₃ concentrations were associated with increased PTH but not with calcium or phosphorus concentrations. Septic foals with 25(OH)D₃ <9.51 ng/mL and 1,25(OH) ₂D₃ <7.09 pmol/L were more likely to die (OR=3.62; 95% CI = 1.1-12.40; OR = 5.41; 95% CI = 1.19-24.52, respectively).

Conclusions

Low 25(OH)D₃ and 1,25(OH)₂D₃ concentrations are associated with disease severity and mortality in hospitalized foals. Vitamin D deficiency may contribute to a pro-inflammatory state in equine perinatal diseases. Hypocalcemia and hyperphosphatemia together with decreased 1,25(OH)₂D₃ but increased PTH concentrations in septic foals indicates that PTH resistance may be associated with the development of these abnormalities.     

1,25 Dihydroxyvitamin D3 Inhibits TGFβ1-Mediated Primary Human Cardiac Myofibroblast Activation

Aims

Epidemiological and interventional studies have suggested a protective role for vitamin D in cardiovascular disease, and basic research has implicated vitamin D as a potential inhibitor of fibrosis in a number of organ systems; yet little is known regarding direct effects of vitamin D on human cardiac cells. Given the critical role of fibrotic responses in end stage cardiac disease, we examined the effect of active vitamin D treatment on fibrotic responses in primary human adult ventricular cardiac fibroblasts (HCF-av), and investigated the relationship between circulating vitamin D (25(OH)D₃) and cardiac fibrosis in human myocardial samples.

Methods and Results

Interstitial cardiac fibrosis in end stage HF was evaluated by image analysis of picrosirius red stained myocardial sections. Serum 25(OH)D₃ levels were assayed using mass spectrometry. Commercially available HCF-av were treated with transforming growth factor (TGF)β₁ to induce activation, in the presence or absence of active vitamin D (1,25(OH)₂D₃). Functional responses of fibroblasts were analyzed by in vitro collagen gel contraction assay. 1,25(OH)₂D₃ treatment significantly inhibited TGFβ₁-mediated cell contraction, and confocal imaging demonstrated reduced stress fiber formation in the presence of 1,25(OH)₂D₃. Treatment with 1,25(OH)₂D₃ reduced alpha-smooth muscle actin expression to control levels and inhibited SMAD2 phosphorylation.

Conclusions

Our results demonstrate that active vitamin D can prevent TGFβ1-mediated biochemical and functional pro-fibrotic changes in human primary cardiac fibroblasts. An inverse relationship between vitamin D status and cardiac fibrosis in end stage heart failure was observed. Collectively, our data support an inhibitory role for vitamin D in cardiac fibrosis.     

Independent Association of Circulating Vitamin D Metabolites with Anemia Risk in Patients Scheduled for Cardiac Surgery

Background

Preoperative anemia is considered an independent risk factor of poor clinical outcome in cardiac surgical patients. Low vitamin D status may increase anemia risk.

Methods

We investigated 3,615 consecutive patients scheduled for cardiac surgery to determine the association between preoperative anemia (hemoglobin [Hb] <12.5 g/dL) and circulating levels of the vitamin D metabolites 25-hydroxyvitamin D (25OHD) and 1,25-dihydroxyvitamin D (1,25[OH]₂D).

Results

Of the study cohort, 27.8 % met the criteria for anemia. In patients with deficient 25OHD levels (<30 nmol/l) mean Hb concentrations were 0.5 g/dL lower than in patients with adequate 25OHD levels (50.0–125 nmol/l; P<0.001). Regarding 1,25(OH)₂D, mean Hb concentrations were 1.2 g/dL lower in the lowest 1,25(OH)₂D category (<40 pmol/l) than in the highest 1,25(OH)₂D category (>70 pmol/l; P<0.001). In multivariable–adjusted logistic regression analyses, the odds ratios for anemia of the lowest categories of 25OHD and 1,25(OH)₂D were 1.48 (95%CI:1.19-1.83) and 2.35 (95%CI:1.86-2.97), compared with patients who had adequate 25OHD levels and 1,25(OH)₂D values in the highest category, respectively. Anemia risk was greatest in patients with dual deficiency of 25OHD and 1,25(OH)₂D (multivariable-adjusted OR = 3.60 (95%CI:2.40-5.40). Prevalence of deficient 25OHD levels was highest in anemia of nutrient deficiency, whereas low 1,25(OH)₂D levels were most frequent in anemia of chronic kidney disease.

Conclusion

This cross-sectional study demonstrates an independent inverse association between vitamin D status and anemia risk. If confirmed in clinical trials, preoperative administration of vitamin D or activated vitamin D (in case of chronic kidney disease) would be a promising strategy to prevent anemia in patients scheduled for cardiac surgery.     

Serum Sphingolipid Variations Associate with Hepatic Decompensation and Survival in Patients with Cirrhosis

Background

Sphingolipids constitute bioactive molecules with functional implications in liver homeostasis. Particularly, ablation of very long chain ceramides in a knockout mouse model has been shown to cause a severe hepatopathy.

Methods

We aimed to evaluate the serum sphingolipid profile of 244 patients with cirrhosis prospectively followed for a median period of 228±217 days via mass spectrometry.

Results

We thereby observed a significant decrease of long and very long chain ceramides, particularly of C24ceramide, in patients with increasing severity of cirrhosis (p<0.001). Additionally, hydropic decompensation, defined by clinical presentation of ascites formation, was significantly correlated to low C24ceramide levels (p<0.001) while a significant association to hepatic decompensation and poor overall survival was observed for low serum concentrations of C24ceramide (p<0.001) as well. Multivariate analysis further identified low serum C24ceramide to be independently associated to overall survival (standard beta = -0.001, p = 0.022).

Conclusions

In our current analysis serum levels of very long chain ceramides show a significant reciprocal correlation to disease severity and hepatic decompensation and are independently associated with overall survival in patients with cirrhosis. Serum sphingolipid metabolites and particularly C24ceramide may constitute novel molecular targets of disease severity, hepatic decompensation and overall prognosis in cirrhosis and should be further evaluated in basic research studies.     

Vitamin D Status Is an Independent Risk Factor for Global Cognitive Impairment in Peritoneal Dialysis Patients

Objective

Vitamin D (VD) deficiency is an independent risk factor for cognitive impairment (CI) in the general population, but VD status in peritoneal dialysis (PD) patients has not been investigated. In this study, we aimed to investigate the relationship between serum VD levels and global and specific cognitive functions in PD patients.

Design and Setting

Cross-sectional study, simultaneously conducted at two PD centers.

Patients

Clinically stable patients (n = 273) undergoing PD for at least 3 months were enrolled over a period of one year.

Main outcome Measures

Demographic and comorbidity data were recorded, and routine biochemical parameters and serum 25-hydroxyvitamin D (25(OH) D) levels of overnight fasted patients were determined. Global cognitive function was assessed by the Modified Mini-Mental State Examination (3MS) score; executive function, by the trail making tests (Trails A and B); and immediate memory, delayed memory, and language ability by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) sub-tests.

Results

In the univariate analysis, serum 25(OH) D levels significantly correlated with 3MS scores (r = -0.139; P = 0.02), and Trail A (r = -0.188; P = 0.002) and B (r = -0.154; P = 0.01) completion times. In the multivariate analysis, 25(OH) D was found to be independently associated with global CI, but not with executive dysfunction. Serum 25(OH) D could not predict scores of immediate/delayed memory and language ability.

Conclusions

VD deficiency is highly prevalent in PD patients and is an independent risk factor for global CI in this patient cohort.     

Vitamin D Status at Birth and Future Risk of Attention Deficit/Hyperactivity Disorder (ADHD)

Objective

To investigate whether children with Attention Deficit/Hyperactivity Disorder have lower levels of Vitamin D₃ at birth than matched controls.

Material

Umbilical cord blood samples collected at birth from 202 children later diagnosed with Attention Deficit/Hyperactivity Disorder were analysed for vitamin D content and compared with 202 matched controls. 25-OH vitamin D₃ was analysed by liquid chromatography tandem mass spectrometry.

Results

No differences in cord blood vitamin D concentration were found between children with Attention Deficit/Hyperactivity Disorder (median 13.0 ng/ml) and controls (median 13.5 ng/ml) (p = 0.43). In a logistic regression analysis, Attention Deficit/Hyperactivity Disorder showed a significant association with maternal age (odds ratio: 0.96, 95% confidence interval: 0.92–0.99) but not with vitamin D levels (odds ratio: 0.99, 95% confidence interval: 0.97–1.02).

Conclusion

We found no difference in intrauterine vitamin D levels between children later developing Attention Deficit/Hyperactivity Disorder and matched control children. However, the statistical power of the study was too weak to detect an eventual small to medium size association between vitamin D levels and Attention Deficit/Hyperactivity Disorder.     

Immune Activation Response in Chronic HIV-Infected Patients: Influence of Hepatitis C Virus Coinfection

Objectives

We have analyzed the parameters (bacterial translocation, immune activation and regulation, presence of HCV coinfection) which could be implicated in an inappropriate immune response from individuals with chronic HIV infection. The influence of them on the evolution of CD4+ T cell count has been investigated.

Patients and methods

Seventy HIV-infected patients [monoinfected by HIV (n = 20), HCV-coinfected (with (n = 25) and without (n = 25) liver cirrhosis)] and 25 healthy controls were included. Median duration of HIV infection was 20 years. HIV- and HCV-related parameters, as well as markers relative to bacterial translocation, monocyte and lymphocyte activation and regulation were considered as independent variables. Dependent variables were the increase of CD4+ T cell count during the follow-up (12 months).

Results

Increased values of bacterial translocation, measured by lipopolysaccharide-binding protein, monocyte and lymphocyte activation markers and T regulatory lymphocytes were detected in HIV-monoinfected and HIV/HCV coinfected patients. Serum sCD14 and IL-6 were increased in HIV/HCV-coinfected patients with liver cirrhosis in comparison with those with chronic hepatitis or HIV-monoinfected individuals. Time with undetectable HIV load was not related with these parameters. The presence of cirrhosis was negatively associated with a CD4+ T cell count increase.

Conclusion

In patients with a chronic HIV infection, a persistent increase of lipopolysaccharide-binding protein and monocyte and lymphocyte modifications are present. HCV-related cirrhosis is associated with more elevated serum concentrations of monocyte-derived markers. Cirrhosis influences the continued immune reconstitution of these patients.     

Altered Calcium and Vitamin D Homeostasis in First-Time Calcium Kidney Stone-Formers

Background

Elevated serum 1,25-dihydroxyvitamin D (1,25(OH)₂D) concentrations have been reported among cohorts of recurrent calcium (Ca) kidney stone-formers and implicated in the pathogenesis of hypercalciuria. Variations in Ca and vitamin D metabolism, and excretion of urinary solutes among first-time male and female Ca stone-formers in the community, however, have not been defined.

Methods

In a 4-year community-based study we measured serum Ca, phosphorus (P), 25-hydroxyvitamin D (25(OH)D), 1,25(OH)₂D, 24,25-dihydroxyvitamin D (24,25(OH)₂D), parathyroid hormone (PTH), and fibroblast growth factor-23 (FGF-23) concentrations in first-time Ca stone-formers and age- and gender frequency-matched controls.

Results

Serum Ca and 1,25(OH)₂D were increased in Ca stone-formers compared to controls (P = 0.01 and P = 0.001). Stone-formers had a lower serum 24,25(OH)₂D/25(OH)D ratio compared to controls (P = 0.008). Serum PTH and FGF-23 concentrations were similar in the groups. Urine Ca excretion was similar in the two groups (P = 0.82). In controls, positive associations between serum 25(OH)D and 24,25(OH)₂D, FGF-23 and fractional phosphate excretion, and negative associations between serum Ca and PTH, and FGF-23 and 1,25(OH)₂D were observed. In SF associations between FGF-23 and fractional phosphate excretion, and FGF-23 and 1,25(OH)₂D, were not observed. 1,25(OH)₂D concentrations associated more weakly with FGF-23 in SF compared with C (P <0.05).

Conclusions

Quantitative differences in serum Ca and 1,25(OH)₂D and reductions in 24-hydroxylation of vitamin D metabolites are present in first-time SF and might contribute to first-time stone risk.     

Association between Plasma 25-Hydroxyvitamin D,Ancestry and Aggressive Prostate Cancer among African Americans and European Americans in PCaP

Background

African Americans (AAs) have lower circulating 25-hydroxyvitamin D3 [25(OH)D3] concentrations and higher prostate cancer (CaP) aggressiveness than other racial/ethnic groups. The purpose of the current study was to examine the relationship between plasma 25(OH)D3, African ancestry and CaP aggressiveness among AAs and European Americans (EAs).

Methods

Plasma 25(OH)D3 was measured using LC-MS/MS (Liquid Chromatography Tandem Mass Spectrometry) in 537 AA and 663 EA newly-diagnosed CaP patients from the North Carolina-Louisiana Prostate Cancer Project (PCaP) classified as having either ‘high’ or ‘low’ aggressive disease based on clinical stage, Gleason grade and prostate specific antigen at diagnosis. Mean plasma 25(OH)D3 concentrations were compared by proportion of African ancestry. Logistic regression was used to calculate multivariable adjusted odds ratios (OR) and 95% confidence intervals (95%CI) for high aggressive CaP by tertile of plasma 25(OH)D3.

Results

AAs with highest percent African ancestry (>95%) had the lowest mean plasma 25(OH)D3 concentrations. Overall, plasma 25(OH)D3 was associated positively with aggressiveness among AA men, an association that was modified by calcium intake (OR_T3vs.T1: 2.23, 95%CI: 1.26–3.95 among men with low calcium intake, and OR_T3vs.T1: 0.19, 95%CI: 0.05–0.70 among men with high calcium intake). Among EAs, the point estimates of the ORs were <1.0 for the upper tertiles with CIs that included the null.

Conclusions

Among AAs, plasma 25(OH)D3 was associated positively with CaP aggressiveness among men with low calcium intake and inversely among men with high calcium intake. The clinical significance of circulating concentrations of 25(OH)D3 and interactions with calcium intake in the AA population warrants further study.     

Significant Effects of Oral Phenylbutyrate and Vitamin D3 Adjunctive Therapy in Pulmonary Tuberculosis: A Randomized Controlled Trial

Background

Development of new tuberculosis (TB) drugs and alternative treatment strategies are urgently required to control the global spread of TB. Previous results have shown that vitamin D₃ (vitD₃) and 4-phenyl butyrate (PBA) are potent inducers of the host defense peptide LL-37 that possess anti-mycobacterial effects.

Objective

To examine if oral adjunctive therapy with 5,000IU vitD₃ or 2x500 mg PBA or PBA+vitD₃ to standard chemotherapy would lead to enhanced recovery in sputum smear-positive pulmonary TB patients.

Methods

Adult TB patients (n = 288) were enrolled in a randomized, double-blind, placebo-controlled trial conducted in Bangladesh. Primary endpoints included proportions of patients with a negative sputum culture at week 4 and reduction in clinical symptoms at week 8. Clinical assessments and sputum smear microscopy were performed weekly up to week 4, fortnightly up to week 12 and at week 24; TB culture was performed at week 0, 4 and 8; concentrations of LL-37 in cells, 25-hydroxyvitamin D₃ (25(OH)D₃) in plasma and ex vivo bactericidal function of monocyte-derived macrophages (MDM) were determined at week 0, 4, 8, 12 and additionally at week 24 for plasma 25(OH)D₃.

Results

At week 4, 71% (46/65) of the patients in the PBA+vitD₃-group (p = 0.001) and 61.3% (38/62) in the vitD₃-group (p = 0.032) were culture negative compared to 42.2% (27/64) in the placebo-group. The odds of sputum culture being negative at week 4 was 3.42 times higher in the PBA+vitD₃-group (p = 0.001) and 2.2 times higher in vitD₃-group (p = 0.032) compared to placebo. The concentration of LL-37 in MDM was significantly higher in the PBA-group compared to placebo at week 12 (p = 0.034). Decline in intracellular Mtb growth in MDM was earlier in the PBA-group compared to placebo (log rank 11.38, p = 0.01).

Conclusion

Adjunct therapy with PBA+vitD₃ or vitD₃ or PBA to standard short-course therapy demonstrated beneficial effects towards clinical recovery and holds potential for host-directed-therapy in the treatment of TB.

Trial Registration

clinicaltrials.gov NCT01580007     

The Prevalence of Vitamin D Deficiency among Cancer Survivors in a Nationwide Survey of the Korean Population

Background

Recent studies have shown that inadequate vitamin D levels are associated with a poor cancer prognosis, but data regarding actual vitamin D levels in cancer survivors are limited. This study investigated the vitamin D levels and prevalence of vitamin D deficiency among Korean cancer survivors compared with non-cancer controls, and identified the factors associated with vitamin D deficiency.

Methods

Using the Korea National Health and Nutrition Examination Survey (KNHANES), 915 cancer survivors and 29,694 controls without a history of cancer were selected. Serum 25(OH)D levels were measured; vitamin D deficiency was defined as 25(OH)D levels less than 20 ng/mL. Chi-square tests and multiple logistic regression analyses were used to evaluate the prevalence of vitamin D deficiency and associated factors.

Results

Vitamin D deficiency was observed in 62.7% of cancer survivors and 67.1% of controls. Among cancer survivors, vitamin D deficiency was most prevalent among 19–44 year olds (76.2%) and among managers, professionals, and related workers (79.3%). Multiple logistic regression analysis revealed that younger cancer survivors and those who work indoors were predisposed to vitamin D deficiency.

Conclusion

Vitamin D deficiency was prevalent among both cancer survivors and controls in Korea. The regular evaluation and management of vitamin D levels is needed for both bone health and general health in cancer survivors.