Assessment of Bone Microarchitecture in Patients with Systemic Mastocytosis and its Association with Clinical and Biochemical Parameters of the Disease.

Patients with systemic mastocytosis (SM) are at high risk of bone deterioration. However, the evaluation of bone microarchitecture in this disease remains unclear. We aimed to assess bone microarchitecture in patients with SM. This was a cross-sectional study of 21 adult patients with SM conducted in a quaternary referral hospital in Sao Paulo, Brazil. A healthy, age-, weight-, and sex-matched cohort of 63 participants was used to provide reference values for bone microarchitecture, assessed by high resolution peripheral quantitative computed tomography (HR-pQCT). Total volumetric bone mineral density (vBMD), cortical vBMD, and cortical thickness at the radius were significantly lower in the control group compared with the SM group (all P < 0.001). Patients with aggressive SM had significantly lower trabecular number (Tb.N) (P = 0.035) and estimated failure load (F.load) (P = 0.032) at the tibia compared with those with indolent SM. Handgrip strength was significantly higher in patients who had more Tb.N at the radius (ρ, 0.46; P = 0.036) and tibia (ρ, 0.49; P = 0.002), and lower who had more trabecular separation at the radius (ρ, -0.46; P = 0.035) and tibia (ρ, -0.52; P = 0.016). Strong and positive associations between F.load (ρ, 0.75; P < 0.001) and stiffness (ρ, 0.70; P < 0.001) at the radius, and between F.load at the tibia (ρ, 0.45; P = 0.038) were observed with handgrip strength. In this cross-sectional study, aggressive SM was more susceptible to bone deterioration compared with indolent SM. In addition, the findings demonstrated that handgrip strength was associated with bone microarchitecture and bone strength.

Social impact of disease parameters and damage accrual in adult Brazilian patients with childhood-onset Systemic Lupus Erythematosus.

OBJECTIVES: To describe the frequency and investigate potential associations of unemployment, need of financial assistance and health-related quality of life in adult patients with childhood-onset Systemic Lupus Erythematosus (cSLE). METHODS: In this multicenter cross-sectional retrospective cohort study including cSLE adult patients, questionnaires were applied evaluating demographic characteristics, medical history, treatment, receipt of government financial assistance, work status, quality of life, economic classification, disease activity, and damage accrual. Disease activity and disease damage were measured at the study visit. RESULTS: Sixty-nine cSLE patients with a median age of 21 years from two Brazilian tertiary centers were included (median disease duration 9 years). Twenty-eight (40.6%) patients were unemployed and 16 (23.2%) were receiving financial assistance or retirement pension. Work unemployment was associated with higher damage scores (OR 1.83, 95% CI 1.08 to 3.09, p = 0.024), and the need of financial assistance was associated with longer disease duration (OR 1.15, 95% CI 1.00 to 1.31, p = 0.045) and worse economic score (OR 0.87, 95% CI 0.77 to 0.99, p = 0.038). Emotional health and body image perception were the most compromised domains of quality of life but showed no association with disease parameters. Disease activity, on the other hand, was inversely associated with symptoms scores (ß = -1.377, p = 0.014) and scores of adverse effects of medications (ß = -1.286, p = 0.020). CONCLUSION: cSLE is a disease with severe outcomes and high social burden that profoundly impacts patients. Damage accrual is a major contributor to unemployment during adulthood and its prevention must be central in the management of cSLE.

Effect of a single high dose of vitamin D3 on cytokines, chemokines, and growth factor in patients with moderate to severe COVID-19.

BACKGROUND: The modulating effect of vitamin D on cytokine concentrations in severe coronavirus disease 2019 (COVID-19) remains unknown. OBJECTIVES: We aimed to investigate the effect of a single high dose of vitamin D3 on cytokines, chemokines, and growth factor in hospitalized patients with moderate to severe COVID-19. METHODS: This is a post hoc, ancillary, and exploratory analysis from a multicenter, double-blind, placebo-controlled, randomized clinical trial. Patients with moderate to severe COVID-19 were recruited from 2 hospitals in São Paulo, Brazil. Of 240 randomly assigned patients, 200 were assessed in this study and randomly assigned to receive a single oral dose of 200,000 IU vitamin D3 (n = 101) or placebo (n = 99). The primary outcome was hospital length of stay, which has been published in our previous study. The prespecified secondary outcomes were serum concentrations of IL-1ß, IL-6, IL-10, TNF-α, and 25-hydroxyvitamin D. The post hoc exploratory secondary outcomes were IL-4, IL-12p70, IL-17A, IFN-γ, granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-8, IFN-inducible protein-10 (IP-10), macrophage inflammatory protein-1ß (MIP-1ß), monocyte chemoattractant protein-1 (MCP-1), vascular endothelial growth factor (VEGF), and leukocyte count. Generalized estimating equations for repeated measures, with Bonferroni's adjustment, were used for testing all outcomes. RESULTS: The study included 200 patients with a mean ± SD age of 55.5 ± 14.3 y and BMI of 32.2 ± 7.1 kg/m2, of which 109 (54.5%) were male. GM-CSF concentrations showed a significant group-by-time interaction effect (P = 0.04), although the between-group difference at postintervention after Bonferroni's adjustment was not significant. No significant effects were observed for the other outcomes. CONCLUSIONS: The findings do not support the use of a single dose of 200,000 IU vitamin D3, compared with placebo, for the improvement of cytokines, chemokines, and growth factor in hospitalized patients with moderate to severe COVID-19.This trial was registered at clinicaltrials.gov as NCT04449718.

Influence of vitamin D status on hospital length of stay and prognosis in hospitalized patients with moderate to severe COVID-19: a multicenter prospective cohort study.

BACKGROUND: Vitamin D acts as a mediator in the immune system regulating antiviral mechanisms and inflammatory processes. Vitamin D insufficiency has been suggested as a potential risk factor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, although its impact on the prognosis of hospitalized patients with coronavirus disease 2019 (COVID-19) remains unclear. OBJECTIVE: This multicenter prospective cohort study was designed to investigate whether serum 25-hydroxyvitamin D [25(OH)D] concentration is associated with hospital length of stay and prognosis in hospitalized patients with COVID-19. METHODS: Patients with moderate to severe COVID-19 (n = 220) were recruited from 2 hospitals in Sao Paulo, Brazil. Serum 25(OH)D concentrations were categorized as follows: <10 ng/mL, 10 to <20 ng/mL, 20 to <30 ng/mL, and ≥30 ng/mL, and <10 ng/mL and ≥10 ng/mL. The primary outcome was hospital length of stay and the secondary outcomes were the rate of patients who required invasive mechanical ventilation and mortality. RESULTS: There were no significant differences in hospital length of stay when the 4 25(OH)D categories were compared (P = 0.120). Patients exhibiting 25(OH)D <10 ng/mL showed a trend (P = 0.057) for longer hospital length of stay compared with those with 25(OH)D ≥10 ng/mL [9.0 d (95% CI: 6.4, 11.6 d) vs. 7.0 d (95% CI: 6.6, 7.4 d)]. The multivariable Cox proportional hazard models showed no significant associations between 25(OH)D and primary or secondary outcomes. CONCLUSIONS: Among hospitalized patients with moderate to severe COVID-19, those with severe 25(OH)D deficiency (<10 ng/mL) exhibited a trend for longer hospital length of stay compared with patients with higher 25(OH)D concentrations. This association was not significant in the multivariable Cox regression model. Prospective studies should test whether correcting severe 25(OH)D deficiency could improve the prognosis of patients with COVID-19.

Effect of a Single High Dose of Vitamin D3 on Hospital Length of Stay in Patients With Moderate to Severe COVID-19: A Randomized Clinical Trial.

Importance: The efficacy of vitamin D3 supplementation in coronavirus disease 2019 (COVID-19) remains unclear. Objective: To investigate the effect of a single high dose of vitamin D3 on hospital length of stay in patients with COVID-19. Design, Setting, and Participants: This was a multicenter, double-blind, randomized, placebo-controlled trial conducted in 2 sites in Sao Paulo, Brazil. The study included 240 hospitalized patients with COVID-19 who were moderately to severely ill at the time of enrollment from June 2, 2020, to August 27, 2020. The final follow-up was on October 7, 2020. Interventions: Patients were randomly assigned to receive a single oral dose of 200 000 IU of vitamin D3 (n = 120) or placebo (n = 120). Main Outcomes and Measures: The primary outcome was length of stay, defined as the time from the date of randomization to hospital discharge. Prespecified secondary outcomes included mortality during hospitalization; the number of patients admitted to the intensive care unit; the number of patients who required mechanical ventilation and the duration of mechanical ventilation; and serum levels of 25-hydroxyvitamin D, total calcium, creatinine, and C-reactive protein. Results: Of 240 randomized patients, 237 were included in the primary analysis (mean [SD] age, 56.2 [14.4] years; 104 [43.9%] women; mean [SD] baseline 25-hydroxyvitamin D level, 20.9 [9.2] ng/mL). Median (interquartile range) length of stay was not significantly different between the vitamin D3 (7.0 [4.0-10.0] days) and placebo groups (7.0 [5.0-13.0] days) (log-rank P = .59; unadjusted hazard ratio for hospital discharge, 1.07 [95% CI, 0.82-1.39]; P = .62). The difference between the vitamin D3 group and the placebo group was not significant for in-hospital mortality (7.6% vs 5.1%; difference, 2.5% [95% CI, -4.1% to 9.2%]; P = .43), admission to the intensive care unit (16.0% vs 21.2%; difference, -5.2% [95% CI, -15.1% to 4.7%]; P = .30), or need for mechanical ventilation (7.6% vs 14.4%; difference, -6.8% [95% CI, -15.1% to 1.2%]; P = .09). Mean serum levels of 25-hydroxyvitamin D significantly increased after a single dose of vitamin D3 vs placebo (44.4 ng/mL vs 19.8 ng/mL; difference, 24.1 ng/mL [95% CI, 19.5-28.7]; P < .001). There were no adverse events, but an episode of vomiting was associated with the intervention. Conclusions and Relevance: Among hospitalized patients with COVID-19, a single high dose of vitamin D3, compared with placebo, did not significantly reduce hospital length of stay. The findings do not support the use of a high dose of vitamin D3 for treatment of moderate to severe COVID-19. Trial Registration: ClinicalTrials.gov Identifier: NCT04449718.

Visceral adipose tissue in granulomatosis with polyangiitis: association with disease activity parameters.

OBJECTIVE: To assess the body composition (BC) of patients with granulomatosis with polyangiitis (GPA) compared to healthy controls, emphasizing visceral adipose tissue (VAT) and associated BC parameters with disease activity, the damage index, and inflammatory parameters in patients with GPA. METHODS: This study was conducted in 43 patients with GPA and 43 healthy controls matched by sex, age, and body mass index (BMI). BC was analyzed using dual-energy X-ray absorptiometry (DXA). The fat mass parameters evaluated were total fat mass (FM), adiposity (%), the fat mass index (FMI: fat mass/ht2), and VAT (g, cm2, cm3). Disease activity was assessed by the Birmingham Vasculitis Activity Score (BVAS). Damage was assessed by the Vasculitis Damage Index (VDI). C-reactive protein (CRP) and the erythrocyte sedimentation rate (ESR) were measured. RESULTS: Comparing patients with GPA with healthy controls, patients had a significantly greater VAT (VAT in g: 685.81 ± 306.10 vs. 581.21 ± 235.57, p = 0.04; VAT in cm2: 142.23 ± 63.48 vs. 119.84 ± 49.54, p = 0.03; VAT in cm3: 741.33 ± 330.97 vs. 628.44 ± 254.66, p = 0.04). Patients with higher VAT (≥ 768 g) had an increased value of ESR (22.77 ± 26.79 vs. 11.57 ± 11.30 mm/1st hour, p = 0.04) and an increased value of BVAS (3.18 ± 4.15 vs. 0.90 ± 1.70, p = 0.01) when compared to patients with less VAT (< 768 g). CONCLUSION: Patients with GPA have altered BC compared to healthy controls. Moreover, higher VAT was associated with disease activity and higher inflammatory markers, suggesting a relationship between GPA activity and adiposity parameters. Key points • Granulomatosis with polyangiitis patients have increased visceral adipose tissue when compared to health controls; • Granulomatosis with polyangiitis patients with higher values of visceral adipose tissue have worse disease activity and higher inflammatory markers; • This paper represents important contribution to the well-studied association between vasculitis and inflammatory markers, adding the role of adipose visceral tissue in the disease physiopathology.