Serum osteoprotegerin and its gene polymorphisms in patients with Takayasu's arteritis: a bicentric cross-sectional study.

INTRODUCTION: Takayasu's arteritis (TAK) patients are at an elevated risk of metabolic syndrome and cardiovascular diseases (CVD). Currently, there are no well-validated biomarkers to assess this risk in this population. Previous research in different cohorts has linked serum levels of osteoprotegerin (OPG) and its polymorphisms to accelerated atherosclerosis and a marker of poor prognosis in CVD. Thus, we assessed this protein as a potential biomarker of CVD in TAK patients. OBJECTIVES: To evaluate the serum levels of OPG and its SNPs (single nucleotide polymorphisms) in TAK patients and healthy controls, and to associate these parameters with clinical data. METHODS: This bicentric cross-sectional study included TAK patients who were compared with healthy individuals (control group). The serum levels of OPG and the frequency of OPG SNPs [1181G > C (rs2073618), 245 A > C (rs3134069), 163T > C (rs3102735), and 209 C > T (rs3134070)] were compared between the both groups and associated with clinical data. RESULTS: In total, 101 TAK patients and 93 controls were included in the study. The serum levels of OPG (3.8 ± 1.9 vs. 4.3 ± 1.8pmol/L, respectively; P = 0.059), and its four polymorphisms were comparable between both groups. In an additional analysis of only TAK patients, serum OPG levels and its four genes were not associated with any CVD parameters, except for higher OPG levels among patients without dyslipidemia. CONCLUSION: No significant differences were observed in serum OPG levels or in the genotype frequencies of OPG SNPs between the patient and control groups. Similarly, no correlation was found between laboratory parameters and clinical data on CVD risk in TAK patients.

Vasculitis induced by biological agents used in rheumatology practice: A systematic review.

Objectives: Biological medications have been used with an increasing frequency to treat rheumatological diseases. Autoimmune events can be induced by these drugs, such as psoriasiform lesions, alopecia, lupus and, vasculitis, which more often affects the skin (small-sized vessels) and eventually other organs. In this review, we describe the clinical profile of patients with vasculitis induced by the main biological agents used in rheumatology. Patients and methods: We performed a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. The PubMed database was used for searching eligible articles. We included case reports, case series, and letter to the editor of patients on anti-tumor necrosis factor-alpha (anti-TNF-a) molecules, as well as tocilizumab, ustekinumab, secukinumab, rituximab, and abatacept, who had vasculitis induced by these agents. Results: Eighty-one articles were included for final analysis (n=89). Twenty-seven patients were using infliximab, 20 adalimumab, 18 etanercept, seven secukinumab, four certolizumab, four rituximab, three golimumab, three ustekinumab, two abatacept, and one tocilizumab. Unspecific leukocytoclastic vasculitis (LCV) was the most common type of vasculitis (n=37), followed by anti-neutrophil cytoplasmic antibody (ANCA)- associated vasculitis (n=16). The medication was replaced with another biological molecule in 23 cases, with only four relapses. In six cases, the biological was maintained, but vasculitis worsened/persisted in one case, being necessary drug removal. Conclusion: Infections, infusion reaction, cancer, and autoimmune events are well-known side effects of biological therapy. This review demonstrates that vasculitis is another adverse effect of this type of therapy, particularly the anti-TNF-a molecules, and LCV the most reported type of vasculitis.

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.

Distinct features of youth-onset primary antiphospholipid syndrome.

BACKGROUND: Characteristics of primary APS (PAPS) in the youth population have never been studied. In contrast with children, pregnancy is genuinely relevant in the youth age, and understanding clinical characteristics of PAPS patients within this specific age stratum may also provide insights regarding the well-known risk of poor obstetric outcomes during the adolescence. OBJECTIVE: To evaluate clinical and laboratory characteristics of patients with youth-onset PAPS (15-24 years) and compare them with adult-onset PAPS (over 24 years old). METHODS: This was a cross-sectional study derived from two rheumatology outpatient clinics. Patients who fulfilled Sidney criteria and who were 15 years of age or older at disease onset were included. Secondary APS patients were excluded. We subdivided patients into two groups: youth- (15-24 years) and adult-onset (over 24 years) and compared them regarding demographic characteristics, criteria and non-criteria manifestations, cardiovascular risk factors, and aPL status. For the pregnancy outcomes analysis, ever-pregnant patients were divided in three groups: youth-onset, early adult-onset (25-34 years), and late adult-onset (35-49 years). RESULTS: A total of 250 consecutive PAPS patients were included. Groups had a comparable female and Caucasian distribution. We found a similar disease duration (14.0±7.9 vs 17.0±10.1 years, p = 0.079) and similar rates of thrombotic arterial (34.2% vs. 42.0%, p = 0.250) and venous events (69.7% vs. 69.5%, p = 0.975) between them. Skin ulcers were more frequent in the youth-onset group (17.1% vs. 4.0%, p = 0.001), whereas nephropathy was less common (1.3% vs. 8.0%, p = 0.039). No differences were observed for the other criteria and non-criteria manifestations. The adult-onset group presented more frequently with hypertension (p = 0.002), hyperlipidemia (p = 0.008), and smoking (p = 0.003). The youth-onset group presented a higher frequency of obstetric events as the first manifestation of PAPS (30.3% vs. 21.7%, p = 0.005), with worse pregnancy outcomes, namely, fetal death (58.5% vs. 46.4% vs. 24.1%, p = 0.012) and premature delivery (35.8% vs. 19.0% vs. 10.3%, p = 0.016). Of note, all groups had a comparable number of pregnancies (2.81±2.52 vs 2.74±2.07, p = 0.899). CONCLUSION: This study provides novel evidence that youth-onset PAPS presents a higher frequency of obstetric complications as its first manifestation, with an increased risk of fetal death and preterm delivery. Early recognition of this condition by obstetricians is essential to improve prognosis.

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.

Cutaneous Vasculitis During Secukinumab Treatment.

Secukinumab is an inhibitor of interleukin IL-17A, and is mainly used in the treatment of psoriasis, psoriatic arthritis and ankylosing spondylitis. Although rarely, this drug may induce paradoxical reactions, such as cutaneous vasculitis. Worldwide, only four previous cases of vasculitis induced by secukinumab have been reported. We herein report the first case described in Brazil of cutaneous vasculitis due to secukinumab in a patient with peripheral spondyloarthritis who demonstrated good resolution after withdrawal of the drug and initiation of etanercept. Clinicians should be aware of this rare but potentially serious adverse effect of secukinumab. LEARNING POINTS: Treatment with biologics can cause vasculitis.The vasculitis may be independent of class of the biologic.Only five cases of vasculitis induced by secukinumab have been reported.

Predictors of HPV incidence and clearance in a cohort of Brazilian HIV-infected women.

Persistent infection with high-risk human papillomavirus (HR-HPV) is necessary for the development of precursor lesions and cervical cancer. HPV infection among women living with HIV/AIDS (WLHA) occurs more frequently, presents a higher rate of persistent infections and an earlier progression to cancer. We aimed to evaluate HR-HPV prevalence, incidence and clearance, and its association with HIV viral suppression, immunological response and other risk factors among WLHA followed at an STD/HIV reference center. This was a cohort study conducted at a reference center for STD/AIDS in Northeastern Brazil from September 2013 to September 2015. Follow-up visits were conducted at 6 and 12 months after enrolment, where socio-epidemiological data were obtained. Cervical samples were collected for conventional cytology and HPV DNA research (PCR COBAS® Roche) in addition to blood samples for CD4+ T lymphocyte count and HIV viral load. We prospectively evaluated 333 women. HR-HPV DNA prevalence was 33.3% at baseline. HPV-16 was present in 5.1%, HPV-18 in 3.9% and 29.4% WLHA had other HR-HPV (31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68). The HR-HPV incidence during the follow-up was 10.8%, at the 6-month visit was 7.7% and at the 12-month visit was 3.7%. Variables associated with HR-HPV incidence were: nulliparity, combined oral contraceptive use and detectable HIV viral load. The HR-HPV clearance rate was 41.7% and was associated with age >30 years and lymphocyte T CD4 count >500 cells/mm3 at enrolment. These findings contribute to the knowledge about a group of women that need more careful HPV screening and describe the association between an efficient immunological response and HIV viral suppression with lower incidence and increased clearance of HR-HPV.

Estudio de frecuencia de los factores de riesgo asociados al desarrollode enfermedad cerebrovascular isquémica no embólica en un hospitalde tercer nivel / Frecuency study of risk factors for cerebrovascular disease development in tertiary hospital in Colombia

Los factores epidemiológicos y las características clínicas de la Enfermedad Cerebrovascular(ECV) varían de acuerdo a factores ambientales, raciales, de género y socioculturales; por tal razón, el conocimientode dichos factores epidemiológicos de riesgo para ECV en nuestra población tiene gran importanciay aporta elementos claves en términos de salud pública.Objetivos. Determinar la frecuencia de los factores de riesgo para el desarrollo de ECV y su tiempo de evolución,así como el número de pacientes que reciben tratamiento para dichos factores de riesgo, la adherenciaal mismo y el seguimiento de recomendaciones de dieta y actividad física.Materiales y métodos. Se realizó un estudio observacional, tipo serie de casos, en pacientes mayores de 18años que consultaron por ECV isquémico en el periodo comprendido entre enero de 2009 hasta septiembrede 2013. Los pacientes se identificaron a través de los códigos CIE-10 contenidos en la base de datos de lainstitución para obtener los registros que incluyeran un diagnóstico principal o relacionado de EnfermedadCerebrovascular Isquémica.Resultados. El promedio de edad fue de 72.7 (SD 12.7) años. Hubo predominio del sexo masculino (50.4%).Conclusiones. La frecuencia de factores de riesgo para ECV parece haber aumentado respecto a publicacionesprevias, posiblemente por modificaciones no saludables en el estilo de vida de la población. El presente estudio brinda información respecto al tratamiento y adherencia farmacológica, ya que realizar un diagnóstico correctode factores de riesgo es muy importante; así mismo, es fundamental instaurar un tratamiento adecuado y, sobre todo, que los pacientes sean adherentes con la terapia para obtener los resultados esperados...

to environmental racial, gender and cultural factors, for this reason, knowledge of the epidemiology of CVDrisk factors in our population is very important and provides key elements in terms of public health.Objective. To determine the frequency of risk factors for the development of CVD and its development time,as well and the number of patients receiving treatment for these risk factors, their adherence to it, in terms offollowing recommendations of diet and physical activity.Materials and Methods. We performed an observational, case series, in patients over 18 years old whoconsulted for ischemic CVD in the period between January 2009 and September 2013. Patients were identifiedby ICD-10 codes in the database for those records or associated with a diagnosis of Ischemic CerebrovascularDisease. Thus, 220 patients met the inclusion criteria. For data collection, a questionnaire was designed to beapplied to each of the records. The information collected was entered in a database in Excel. Descriptive analysiswas performed using STATA statistical software version 12.0. Measures of central tendency and dispersionfor continuous variables and frequencies and proportions for nominal and ordinal variables were estimated...