Risk factors for mortality in 1528 Brazilian childhood-onset systemic lupus erythematosus patients.

OBJECTIVES: To identify associations between mortality in cSLE patients and their characteristics: clinical and laboratory features, disease activity and damage scores, and treatment; to evaluate risk factors associated with mortality in cSLE; and to determine the most frequent causes of death in this group of patients. METHODS: We performed a multicenter retrospective cohort using data from 1,528 cSLE patients followed in 27 pediatric rheumatology tertiary centers in Brazil. Patients' medical records were reviewed according to a standardized protocol, in which information regarding demographic and clinical features, disease activity and damage scores, and treatment were collected and compared between deceased cSLE patients and survivors. Univariate and multivariate analyses by Cox regression model were used to calculate risk factors for mortality, whereas survival rates were analyzed by Kaplan-Meier plots. RESULTS: A total of 63/1,528 (4.1%) patients deceased, 53/63 were female (84.1%), median age at death was 11.9 (9.4-13.1) years and median time interval between cSLE diagnosis and death was 3.2 (0.5-5.3) years. Sepsis was the main cause of death in 27/63 (42.8%) patients, followed by opportunistic infections in 7/63 (11.1%), and alveolar hemorrhage in 6/63 (9.5%) patients. The regression models resulted in neuropsychiatric lupus (NP-SLE) (HR = 2.56, 95% CI = 1.48-4.42) and chronic kidney disease (CKD) (HR = 4.33, 95% CI = 2.33-4.72), as risk factors significantly associated with mortality. Overall patient survival after cSLE diagnosis at 5, 10, and 15 years were 97%, 95.4%, and 93.8%, respectively. CONCLUSIONS: This study confirmed that the recent mortality rate in cSLE in Brazil is low, but still of concern. NP-SLE and CKD were the main risk factors for mortality, indicating that the magnitude of these manifestations was significantly high.

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.

The new 2019-EULAR/ACR classification criteria specific domains at diagnosis can predict damage accrual in 670 childhood-onset systemic lupus erythematosus patients.

OBJECTIVE: To evaluate if the 2019-European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) criteria at diagnosis of childhood-onset systemic lupus erythematosus (cSLE) are associated with higher rates of early damage scored by Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index (SDI). METHODS: This retrospective multicenter study included 670 cSLE patients with ≤5 years of disease duration. All patients fulfilled both 2019-EULAR/ACR and 1997-ACR classification criteria. Total score of 2019-EULAR/ACR criteria and each of its specific domains were assessed at diagnosis as predictors of damage accrual at the last visit, according to the presence of any organ damage (defined by SDI ≥ 1). RESULTS: Median disease duration was 2.8 (IQR 1.8-3.8) years and 200 (29.9%) patients had at least one organ damage (SDI ≥ 1). The most frequent domains were neuropsychiatric (12%), renal (7%), and musculoskeletal (6%). There was a higher frequency of renal (58% vs 43%, p = 0.0004) and neuropsychiatric domain (21% vs 7%, p < 0.0001) of 2019-EULAR/ACR criteria in patients with damage (SDI ≥ 1) compared to those without damage (SDI = 0). Patients scoring renal or neuropsychiatric domains of the 2019-EULAR/ACR criteria at diagnosis were associated with renal damage (odds ratio 9.701, 95% confidence interval 3.773-24.941, p < 0.001) or neuropsychiatric damage (OR 9.480, 95% CI 5.481-16.399, p<0.0001) at latest visit, respectively. cSLE patients with positive anti-dsDNA at diagnosis were also associated with renal damage by the latest visit (OR 2.438, 95% CI 1.114-5.3381, p = 0.021). Constitutional, hematologic, mucocutaneous, serosal, and musculoskeletal domains and specific criteria as well as other immunologic criteria were not associated with damage accrual. Median of SLEDAI-2K was significantly higher in patients with global damage (19.5 (2-51) vs 14 (0-51), p<0.001). 2019-EULAR/ACR score >25 was associated with more overall (SDI ≥ 1) (38% vs 25%, p = 0.0002) and renal damage (11% vs 5%, p = 0.023). CONCLUSIONS: The 2019-EULAR/ACR criteria at diagnosis were associated with a higher rate of early damage in cSLE patients, especially for renal and neuropsychiatric damage. Of note, damage was particularly associated with high disease activity at diagnosis and 2019-EULAR/ACR score >25.

Bone erosions associated with systemic bone loss on HR-pQCT in women with longstanding polyarticular juvenile idiopathic arthritis.

OBJECTIVES: To analyze longstanding polyarticular juvenile idiopathic arthritis (pJIA) for possible associations between localized bone damage (erosions), and systemic bone loss. Besides, to compare the systemic bone mass of pJIA with healthy controls. METHODS: Thirty-four pJIA women and 99 healthy controls (HC) were included. Radius and tibia of all subjects were scanned by HR-pQCT. Volumetric bone mineral density (vBMD), bone microarchitecture, and -finite element parameters were analyzed. Patients underwent HR-pQCT of 2nd and 3rd metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints of the dominant hand, for bone erosions quantification. RESULTS: The mean age of patients was 31.5 ± 7.4yrs with a mean disease duration of 21.7 ± 9.2yrs. Bone erosions were detectable in 79% of patients. The number of bone erosions was positively correlated with cortical porosity (Ct.Po) at tibia (r = 0.575, p = 0.001), and radius (r = 0.423, p = 0.018); and negatively correlated with cortical vBMD at tibia (r=-0.420, p = 0.015). In a logistic regression analysis, adjusted for anti-CCP, the presence of bone erosions was independently associated with Ct.Po at radius (p = 0.018) and cortical vBMD at tibia (p = 0.020). Moreover, cortical and trabecular vBMD, trabecular number, and µ-finite element parameters were decreased in patients compared to HC (p < 0.05). CONCLUSION: Bone erosions in longstanding pJIA women were associated with decreased cortical bone parameters, and these patients showed systemic bone impairment at peripheral sites compared with healthy controls.

Association of Appendicular Lean Mass, and Subcutaneous and Visceral Adipose Tissue With Mortality in Older Brazilians: The São Paulo Ageing & Health Study.

Body composition changes as a result of ageing may impact the survival of older adults. However, its influence on mortality risk is uncertain. Currently, the best method for body composition analysis in clinical practice is DXA. Nonetheless, the few studies on body composition by DXA and mortality risk in the elderly have some limitations. We investigated the association between body composition by DXA and mortality in a cohort of elderly subjects. Eight hundred thirty-nine community-dwelling subjects (516 women, 323 men) ≥ 65 years of age were assessed by a questionnaire, clinical data, laboratory exams, and body composition by DXA at baseline. Total fat and its components (eg, visceral adipose tissue [VAT]) were estimated. Appendicular lean mass (ALM) adjusted for fat and ALM divided by height² was used to ascertain the presence of low muscle mass (LMM). Mortality was recorded during follow-up. Multivariate logistic regression was used to compute ORs for all-cause and cardiovascular mortality. Over a mean follow-up of 4.06 ± 1.07 years, there were 132 (15.7%) deaths. In men, after adjustment for relevant variables, the presence of LMM (OR, 11.36, 95% CI, 2.21 to 58.37, P = 0.004) and VAT (OR, 1.99, 95% CI, 1.38 to 2.87, P < 0.001, for each 100-g increase) significantly increased all-cause mortality risk, whereas total fat, measured by the fat mass index, was associated with decreased mortality risk (OR, 0.48, 95% CI, 0.33 to 0.71, P < 0.001). Similar results were observed for cardiovascular mortality. In women, only LMM was a predictor of all-cause (OR, 62.88, 95% CI, 22.59 to 175.0, P < 0.001) and cardiovascular death (OR, 74.54, 95% CI, 9.72 to 571.46, P < 0.001). LMM ascertained by ALM adjusted for fat and fat mass by itself are associated with all-cause and cardiovascular mortality risk in the elderly. Visceral and subcutaneous fat have opposite roles on mortality risk in elderly men. Thus, DXA is a promising tool to estimate risk of mortality in the elderly. © 2019 American Society for Bone and Mineral Research.

Treatment of Human Immunodeficiency Virus Infection With Tenofovir Disoproxil Fumarate-Containing Antiretrovirals Maintains Low Bone Formation Rate, But Increases Osteoid Volume on Bone Histomorphometry.

Bone mineral density (BMD) loss is a known complication of human immunodeficiency virus (HIV) infection and its treatment, particularly with tenofovir disoproxil fumarate (TDF)-containing antiretroviral regimens. Although renal proximal tubular dysfunction and phosphaturia is common with TDF, it is unknown whether BMD loss results from inadequate mineralization. We evaluated change in BMD by dual-energy X-ray absorptiometry (DXA) and bone histomorphometry by tetracycline double-labeled transiliac crest biopsies in young men living with HIV before (n = 20) and 12 months after (n = 16) initiating TDF/lamivudine/efavirenz. We examined relationships between calciotropic hormones, urinary phosphate excretion, pro-inflammatory and pro-resorptive cytokines, and bone remodeling-related proteins with changes in BMD and histomorphometry. Mean age was 29.6 ± 5.5 years, with mean CD4 + T cell count of 473 ± 196 cells/mm3 . At baseline, decreased bone formation rate and increased mineralization lag time were identified in 16 (80%) and 12 (60%) patients, respectively. After 12 months, we detected a 2% to 3% decrease in lumbar spine and hip BMD by DXA. By histomorphometry, we observed no change in bone volume/total volume (BV/TV) and trabecular parameters, but rather, increases in cortical thickness, osteoid volume, and osteoblast and osteoclast surfaces. We did not observe significant worsening of renal phosphate excretion or mineralization parameters. Increases in PTH correlated with decreased BMD but not histomorphometric parameters. Overall, these data suggest abnormalities in bone formation and mineralization occur with HIV infection and are evident at early stages. With TDF-containing antiretroviral therapy (ART), there is an increase in bone remodeling, reflected by increased osteoblast and osteoclast surfaces, but a persistence in mineralization defect, resulting in increased osteoid volume. © 2019 American Society for Bone and Mineral Research.

Anti-SARS-CoV-2 inactivated vaccine in patients with ANCA-associated vasculitis: Immunogenicity, safety, antibody decay and the booster dose

Abstract Objective: To evaluate inactivated CoronaVac prime vaccination, antibody decay, booster dose, and safety in ANCA-Associated Vasculitis (AAV) patients. Methods: Fifty-three AAV patients and 106 Controls (CG) received CoronaVac on days: D0 (first dose), D28(second dose), and D210 (booster dose, 32 AAV: 32 CG). The primary outcome was immunogenicity after the second vaccine dose (day 69) assessed by Seroconversion Rates (SC) of anti-SARS-CoV-2 S1/S2 IgG and Neutralizing Antibodies (NAb). Secondary outcomes were safety, immunogenicity (D28/D240), 6-months antibody decay (D210) and the booster dose response (D240). Results: At D69 SC (65.1% vs. 96.8%, p = 0.0001), GMT (21.3 UA/mL vs. 67.7 UA/mL, p < 0.001) and NAb- positivity (53.7% vs. 80.6%, p = 0.001) were moderate but lower in naïve-AAV patients than CG. Patients without SC used more often IS (93.3% vs. 53.3%, p = 0.015), mycophenolate mofetil (20% vs. 0%, p = 0.037) and prednisone (60.0% vs. 28.6%, p = 0.057) than seroconverted. NAb negativity in AAV patients was associated with prednisone treatment (57.9% vs. 18.2%, p = 0.015) and IS (84.2% vs. 55.0%, p = 0.046). Logistic regression analysis models showed that only prednisone was associated with lower seroconversion (OR = 0.2, 0,95% CI 0.05-0.86, p = 0.030) and with lower NAb positivity (OR = 0.2, 0,95% CI 0.05-0.88, p = 0.034). After six months (D69-D210) a decrease in IgG positivity occurred in 32 AAV patients (15.7%, p = 0.074) and 32 CG (18.7%, p = 0.041). For the NAb positivity, the 6-month decrease was not significant (p = 0.114) whereas a major reduction occurred for CG (p < 0.001). A booster dose (D240) resulted in an increment in IgG-positivity (21.9%, p = 0.023) and NAb-positivity (34.4%, p = 0.006) in AAV patients. No moderate/severe adverse events attributable to the vaccine were observed. Conclusion: This study provides novel data on the excellent safety and moderate immunogenicity of CoronaVac in AAV patients. A six-month mild antibody waning was observed with a good response to the booster dose, although levels remained lower than CG (CoronavRheum-NCT04754698).

Bone Mineral Density and Parathyroid Hormone as Independent Risk Factors for Mortality in Community-Dwelling Older Adults: A Population-Based Prospective Cohort Study in Brazil. The São Paulo Ageing & Health (SPAH) Study.

Previous studies have shown a relationship between osteoporosis and increased mortality risk. However, none of these studies performed a concomitant evaluation of the parathyroid hormone (PTH)-calcium-vitamin D axis and bone mass to accurately determine the contribution of each of these parameters to survival in older subjects. Thus, we sought to investigate the association between bone parameters and mortality in a longitudinal, prospective, population-based cohort of 839 elderly subjects. Clinical data (including history of fractures and cardiovascular events) were assessed using a specific questionnaire. Laboratory exams, including serum 25OHD and PTH, were also performed. Bone mineral density (BMD) at the lumbar spine and hip were evaluated using DXA. All analyses were performed at baseline (2005 to 2007). Mortality was recorded during follow-up. Multivariate Cox proportional regression was used to compute hazard ratios for all-cause and cardiovascular mortality. Over a mean 4.06 ± 1.07 years, there were 132 (15.7%) deaths. These individuals were compared to 707 subjects who were alive at the end of the coverage period for mortality data collection. In a multivariate Cox proportional hazards model, age (HR 1.32; 95% CI, 1.13 to 1.55; p = 0.001, for each 5-year increase), male gender (HR 1.90; 95% CI, 1.30 to 2.79; p = 0.001), recurrent falls (more than two in the previous year; HR 1.65; 95% CI, 1.06 to 2.56; p = 0.026), diabetes mellitus (HR 2.17; 95% CI, 1.46 to 3.21; p < 0.001), low physical activity score (HR 1.78; 95% CI, 1.14 to 2.79; p = 0.011), prior cardiovascular event (HR 1.76; 95% CI, 1.18 to 2.63; p = 0.006), total hip BMD (HR 1.41; 95% CI, 1.15 to 1.72; p = 0.001, per each 1 SD decrease), and intact PTH (iPTH) (HR 1.06; 95% CI, 1.04 to 1.08; p < 0.001, per each 10 pg/mL increase) were independently associated with all-cause mortality. The subjects in the highest quartile of PTH (>49 pg/mL) were at a higher risk of cardiovascular death (HR 3.09; 95% CI, 1.36 to 6.99; p = 0.007) compared with the subjects in the lowest quartile (<26 pg/mL). Low BMD and higher PTH were significantly associated with mortality in community-dwelling older adults. These findings support the notion that careful screening of these bone parameters might lead to better management of older patients and improve outcomes in this population. © 2016 American Society for Bone and Mineral Research.

Current knowledge regarding Asherson's syndrome.

Catastrophic antiphospholipid (Asherson's) syndrome (CAPS) is known to be a severe variant (1%) of antiphospholipid syndrome, with a high rate of mortality (50%). The distinguishing feature of CAPS is microvascular thromboses in the presence of antiphospholipid antibodies. Molecular mimicry between beta2-glycoprotein I and infectious agents, endothelial cell activation and reduced fibrinolysis are the most frequently described pathophysiological mechanisms. Genetic risk factors have also been implicated in the onset of CAPS, although these have not yet been identified. There have been no randomized, controlled trials evaluating the efficacy of any medication on CAPS; however, when CAPS is suspected, aggressive multimodal treatment is required. Patients who receive a combination of anticoagulation therapy, glucocorticosteroids and plasma exchange with or without intravenous immunoglobulin show the best survival rates. Herein, we review the clinical and laboratory findings, diagnostic criteria, pathophysiology, treatment and prognosis of CAPS.

Bone densitometry by dual-energy X-ray absorptiometry (DXA) in preterm newborns compared with full-term peers in the first six months of life / Densitometria óssea de dupla absorção de raio-X (DXA) em crianças nascidas pré-termo comparada com seus pares a termo nos primeiros 6 meses

OBJECTIVES: To longitudinally assess bone mineral content (BMC), bone mineral density (BMD), and whole-body lean mass obtained through bone densitometry by dual-energy X-ray absorptiometry (DXA) in preterm newborns (PTNs) and compare them with full-term newborns (FTNs) from birth to 6 months of corrected postnatal age. METHODS: A total of 28 adequate for gestational age (AGA) newborns were studied: 14 preterm and 14 full-term newborns. DXA was used to determine BMC, BMD, and lean mass in three moments: 40 weeks corrected post-conceptual age, as well as 3 and 6 months of corrected postnatal age. PTNs had gestational age ≤ 32 weeks at birth and were fed their mother's own milk or milk from the human milk bank. RESULTS: All infants had an increase in BMC, BMD, and lean body mass values during the study. PTNs had lower BMC, BMD, and lean mass at 40 weeks of corrected post-conceptual age in relation to FTNs (p < 0.001, p < 0.001, p = 0.047, respectively). However, there was an acceleration in the mineralization process of PTNs, which was sufficient to achieve the normal values of FTNs at 6 months of corrected age. CONCLUSIONS: This study suggests that bone densitometry by dual-energy X-ray absorptiometry is a good method for the assessment of body composition parameters at baseline, and at the follow-up of these PTNs. .

OBJETIVOS: Avaliar longitudinalmente o conteúdo mineral ósseo (CMO), a densidade mineral óssea (DMO) e a massa magra do corpo inteiro obtidos através da densitometria óssea de dupla absorção de Raios-X (DXA) em recém-nascidos pré-termo (RNPT) e comparar com seus pares a termo (RNT) desde o nascimento até 6 meses de idade pós-natal corrigida. MÉTODOS: Foram estudados 28 recém-nascidos adequados para a idade gestacional: 14 recém-nascidos pré-termo e 14 recém-nascidos a termo. Utilizando-se a DXA, foram determinados CMO, DMO e massa magra em três momentos: 40 semanas de idade pós-concepcional corrigida, 3 e 6 meses de idade pós-natal corrigida. Os recém-nascidos pré-termo apresentavam ao nascimento uma idade gestacional igual ou inferior a 32 semanas e receberam leite da própria mãe ou leite humano de banco. RESULTADOS: Todos os recém-nascidos apresentaram um aumento nos valores de CMO, DMO e massa magra durante o estudo. Os recém-nascidos pré-termo apresentaram menor CMO, DMO e massa magra, com 40 semanas de idade pós-concepcional corrigida, em relação aos recém-nascidos a termo (p < 0,001, p < 0,001, e p = 0,047, respectivamente). Entretanto, houve uma aceleração no processo de mineralização nos pré-termos, suficiente para atingirem os valores normais do recém-nascidos a termo aos 6 meses de idade corrigida. CONCLUSÕES: Este estudo sugere que a densitometria óssea de dupla absorção de Raios-X constitui um bom método para a avaliação dos parâmetros de composição corporal no início e no seguimento destes recém-nascidos pré-termo. .