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.

Exercise modifies hypothalamic connectivity and brain functional networks in women after bariatric surgery: a randomized clinical trial.

BACKGROUND: Obesity is a disease that may involve disrupted connectivity of brain networks. Bariatric surgery is an effective treatment for obesity, and the positive effects on obesity-related conditions may be enhanced by exercise. Herein, we aimed to investigate the possible synergistic effects of Roux-en-Y Gastric Bypass (RYGB) and exercise training on brain functional networks. METHODS: Thirty women eligible for bariatric surgery were randomly assigned to a Roux-en-Y gastric bypass (RYGB: n = 15, age = 41.0 ± 7.3 years) or RYGB plus Exercise Training (RYGB + ET: n = 15, age = 41.9 ± 7.2 years). Clinical, laboratory, and brain functional connectivity parameters were assessed at baseline, and 3 (POST3) and 9 months (POST9) after surgery. The 6-month, three-times-a-week, exercise intervention (resistance plus aerobic exercise) was initiated 3 months post-surgery (for RYGB + ET). RESULTS: Exercise superimposed on bariatric surgery (RYGB + ET) increased connectivity between hypothalamus and sensorial regions (seed-to-voxel analyses of hypothalamic connectivity), and decreased default mode network (DMN) and posterior salience (pSAL) network connectivity (ROI-to-ROI analyses of brain networks connectivity) when compared to RYGB alone (all p-FDR < 0.05). Increases in basal ganglia (BG) network connectivity were only observed in the exercised training group (within-group analyses). CONCLUSION: Exercise training is an important component in the management of post-bariatric patients and may improve the hypothalamic connectivity and brain functional networks that are involved in controlling food intake. TRIAL REGISTRATION: Clinicaltrial.gov: NCT02441361.

Chronic kidney disease in patients with childhood-onset systemic lupus erythematosus.

BACKGROUND: Lupus nephritis (LN) is a frequent manifestation of childhood-onset systemic lupus erythematosus (cSLE) with a potential risk for kidney failure and poor outcomes. This study aimed to evaluate stages III, IV, and V of chronic kidney disease (CKD) and investigate risk factors for CKD in cSLE patients. METHODS: We performed a nationwide observational cohort study in 27 pediatric rheumatology centers, including medical charts of 1528 cSLE patients. Data were collected at cSLE diagnosis, during follow-up, and at last visit or death, between September 2016 and May 2019. RESULTS: Of 1077 patients with LN, 59 (5.4%) presented with CKD, 36/59 (61%) needed dialysis, and 7/59 (11.8%) were submitted for kidney transplantation. After Bonferroni's correction for multiple comparisons (p < 0.0013), determinants associated with CKD were higher age at last visit, urinary biomarker abnormalities, neuropsychiatric involvement, higher scores of disease activity at last visit and damage index, and more frequent use of methylprednisolone, cyclosporine, cyclophosphamide, and rituximab. In the regression model analysis, arterial hypertension (HR = 15.42, 95% CI = 6.12-38.83, p ≤ 0.001) and biopsy-proven proliferative nephritis (HR = 2.83, 95%CI = 1.70-4.72, p ≤ 0.001) increased the risk of CKD, while children using antimalarials had 71.0% lower CKD risk ((1.00-0.29) × 100%) than children not using them. The Kaplan-Meier comparison showed lower survival in cSLE patients with biopsy-proven proliferative nephritis (p = 0.02) and CKD (p ≤ 0.001). CONCLUSIONS: A small number of patients manifested CKD; however, frequencies of dialysis and kidney transplantation were relevant. This study reveals that patients with cSLE with hypertension, proliferative nephritis, and absence of use of antimalarials exhibited higher hazard rates of progression to CKD. A higher resolution version of the Graphical abstract is available as Supplementary information.

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).

Immunogenicity decay and case incidence six months post Sinovac-CoronaVac vaccine in autoimmune rheumatic diseases patients.

The determination of durability and vaccine-associated protection is essential for booster doses strategies, however data on the stability of SARS-CoV-2 immunity are scarce. Here we assess anti-SARS-CoV-2 immunogenicity decay and incident cases six months after the 2nd dose of Sinovac-CoronaVac inactivated vaccine (D210) in 828 autoimmune rheumatic diseases patients compared with 207 age/sex-balanced control individuals. The primary outcome is the presence of anti-S1/S2 SARS-CoV-2 IgG at 6 months compared to 6 weeks after 2nd vaccine dose for decay evaluation. Secondary outcomes are presence of neutralizing antibodies, percent inhibition by neutralizing, geometric mean titers and cumulative incident cases at 6 months after 2nd dose. Anti-S1/S2 IgG positivity and titers reduce to 23.8% and 38% in patients (p < 0.001) during the six-month follow up and 20% and 51% in controls (p < 0.001), respectively. Neutralizing antibodies positivity and percent inhibition declines 41% and 54% in patients (p < 0.001) and 39.7% and 47% in controls (p < 0.001). Multivariate logistic regression analysis show males (OR = 0.56;95% CI0.40-0.79), prednisone (OR = 0.56; 95% CI0.41-0.76), anti-TNF (OR = 0.66;95% CI0.45-0.96), abatacept (OR = 0.29; 95% CI0.15-0.56) and rituximab (OR = 0.32;95% CI0.11-0.90) associate with a substantial reduction in IgG response at day 210 in patients. Although cellular immunity was not assessed, a decrease of COVID-19 cases (from 27.5 to 8.1/100 person-years; p < 0.001) is observed despite the concomitant emergence and spread of the Delta variant. Altogether we show a reduction in immunity 6-months of Sinovac-CoronaVac 2nd dose, particularly in males and those under immunosuppressives therapies, without a concomitant rise in COVID-19 cases. (CoronavRheum clinicaltrials.gov:NCT04754698).

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.

Is positron emission tomography/magnetic resonance imaging a reliable tool for detecting vascular activity in treated childhood-onset Takayasu's arteritis? A multicentre study.

OBJECTIVES: Toassess whether 18F-fluordeoxiglucose (18F-FDG) PET/MRI) with angiographic sequences can contribute to detecting vessel wall inflammation in patients with childhood-onset Takayasu's arteritis (c-TA) under immunosuppressive therapy. METHODS: A three-centre cross-sectional study was conducted. 18F-FDG PET/MRI scans were performed in c-TA patients and in oncologic patients, who served as the control group. Clinical and laboratory characteristics were also analysed. RESULTS: Seventeen c-TA patients (65% females) between the ages of 6 and 21 years with a mean disease duration of 9.4 years were recruited. Only one patient presented clinical disease activity and six (35.6%) had increased ESR and/or CRP levels. The most frequent magnetic resonance angiography (MRA) findings were stenosis and thickening, observed in 82.4 and 70.6% of c-TA patients, respectively. 18F-FDG PET revealed 18F-FDG uptake greater than the liver in at least one arterial segment in 15 (88.2%) patients in a qualitative analysis and a median maximum standardized uptake value (SUVmax) of 3.22 (interquartile range 2.76-3.69) in a semi-quantitative analysis. c-TA patients presented significantly higher SUVmax values than oncologic patients (P < 0.001). A positive correlation between SUVmax and CRP levels (ρ = 0.528, P = 0.029) was seen. CONCLUSION: A state-of-the-art imaging modality was used in c-TA patients and revealed a strong arterial FDG uptake even in patients in apparent remission. We suppose that this finding may represent silent activity in the vessel wall; however, we cannot exclude the possibility of arterial remodelling. Importantly, a negative imaging scan may help in immunosuppression withdrawal in daily clinical practice.

Does [18F]F-FDG-PET/MRI add metabolic information to magnetic resonance image in childhood-onset Takayasu's arteritis patients? A multicenter case series

Abstract Background: The observation that 2-deoxy-2[18F]fluoro-D-glucose-positron emission tomography/magnetic resonance imaging ([18F]F-FDG-PET/MRI) revealed high-grade arterial wall FDG uptake, without arterial wall thickening with contrast-enhancement, in a considerable number of c-TA patients in our previous study, encouraged us to compare patients with both PET and MR angiography (MRA) positives, with those with PET positive but MRA negative. Our aim was to evaluate the relevance of these two imaging modalities together. Methods: A three-center cross-sectional study with 17 patients who fulfilled the EULAR/PRINTO/PReS criteria for c-TA and who underwent [18F]F-FDG-PET/MRI was previously performed. Herein we compared patients/vessels with positive PET (arterial wall 18F-FDG uptake higher than liver) and positive MRA (arterial wall thickening with contrast-enhancement)—group 1, with those with positive PET but negative MRA—group 2. Results: Median disease duration of 17 c-TA patients was 10.4 years. Nine patients were classified as group 1 and six as group 2. Median of metabolic inflammatory volume (MIV) of all arterial segments was significantly higher in group 1 (2346 vs. 1177 cm3; p = 0.036). Fifty-four (19%) from 284 available arterial segments presented positive findings in vessel wall in one or both images. Positive findings were concordant between PET and MRA in only 13% arterial segments (group 1); most changes (28-59.6%) that were discordant between both images, were positive in PET and negative in MRA (group 2). Conclusions: Our study demonstrated that [18F]F-FDG-PET/MRI added information about inflammation in vessel wall of c-TA patients. Prospective multicenter studies are needed in order to get solid data to guide immunosuppressive tapering and withdrawal.

Mortality predictors in ANCA-associated vasculitis: Experience of a Brazilian monocentric cohort of a rheumatology center.

ABSTRACT: The mortality rate of patients with anti-neutrophil cytoplasm antibody -associated vasculitis (AAV) is higher than the general population. To date, no studies have evaluated the factors associated with unfavorable outcomes in Brazilian patients, who represent a miscegenated population. Our objective was to identify clinical and laboratory features associated with mortality in Brazilian patients with AAV.One hundred twenty eight patients fulfilling the American College of Rheumatology and Chapel Hill Classification Criteria followed between 2000 and 2018 in our Rheumatology Outpatient Clinics were included. Data were obtained from an ongoing electronic database. Patients were divided into 2 groups (dead or alive in 2018), and disease activity (Birmingham vasculitis activity score [BVAS]), vasculitis-related damage (VDI), and laboratory parameters were compared at the most recent attendance and at the last attendance before death.Of the 128 patients followed, 78.9% had granulomatosis with polyangiitis, 16.4% had eosinophilic granulomatosis with polyangiitis, and 4.6% had microscopic polyangiitis. In 2018, 78 patients were alive, 25 had died, and 25 had lost contact. The main cause of death was infection. According to the univariate analysis, the Birmingham vasculitis activity score, VDI, and glucocorticoid dose were higher in the group of patients who died. Laboratorial features related to mortality were creatinine, hemoglobin, erythrocyte sedimentation ratio, and C-reactive protein (CRP). Logistic regression analysis showed that high VDI, creatinine levels, and CRP levels were independent factors associated with mortality. Survival was significantly decreased in patients with renal impairment.This is the first study to use this approach performed in a Brazilian population and it showed that damage index, renal impairment, and CRP levels were associated with mortality in a miscegenated population with AAV.

A randomized clinical trial on the effects of exercise on muscle remodelling following bariatric surgery.

BACKGROUND: Muscle atrophy and strength loss are common adverse outcomes following bariatric surgery. This randomized, controlled trial investigated the effects of exercise training on bariatric surgery-induced loss of muscle mass and function. Additionally, we investigated the effects of the intervention on molecular and histological mediators of muscle remodelling. METHODS: Eighty women with obesity were randomly assigned to a Roux-en-Y gastric bypass (RYGB: n = 40, age = 42 ± 8 years) or RYGB plus exercise training group (RYGB + ET: n = 40, age = 38 ± 7 years). Clinical and laboratory parameters were assessed at baseline, and 3 (POST3) and 9 months (POST9) after surgery. The 6 month, three-times-a-week, exercise intervention (resistance plus aerobic exercise) was initiated 3 months post-surgery (for RYGB + ET). A healthy, lean, age-matched control group was recruited to provide reference values for selected variables. RESULTS: Surgery resulted in a similar (P = 0.66) reduction in lower-limb muscle strength in RYGB and RYGB+ET (-26% vs. -31%), which was rescued to baseline values in RYGB + ET (P = 0.21 vs. baseline) but not in RYGB (P < 0.01 vs. baseline). Patients in RYGB+ET had greater absolute (214 vs. 120 kg, P < 0.01) and relative (2.4 vs. 1.4 kg/body mass, P < 0.01) muscle strength compared with RYGB alone at POST9. Exercise resulted in better performance in timed-up-and-go (6.3 vs. 7.1 s, P = 0.05) and timed-stand-test (18 vs. 14 repetitions, P < 0.01) compared with RYGB. Fat-free mass was lower (POST9-PRE) after RYBG than RYGB + ET (total: -7.9 vs. -4.9 kg, P < 0.01; lower-limb: -3.8 vs. -2.7 kg, P = 0.02). Surgery reduced Types I (~ - 21%; P = 0.99 between-group comparison) and II fibre cross-sectional areas (~ - 27%; P = 0.88 between-group comparison), which were rescued to baseline values in RYGB+ET (P > 0.05 vs. baseline) but not RYGB (P > 0.01 vs. baseline). RYGB + ET showed greater Type I (5187 vs. 3898 µm2 , P < 0.01) and Type II (5165 vs. 3565 µm2 , P < 0.01) fCSA than RYGB at POST9. RYGB + ET also resulted in increased capillarization (P < 0.01) and satellite cell content (P < 0.01) than RYGB at POST9. Gene-set normalized enrichment scores for the muscle transcriptome revealed that the ubiquitin-mediated proteolysis pathway was suppressed in RYGB + ET at POST9 vs. PRE (NES: -1.7; P < 0.01), but not in RYGB. Atrogin-1 gene expression was lower in RYGB + ET vs. RYGB at POST9 (0.18 vs. 0.71-fold change, P < 0.01). From both genotypic and phenotypic perspectives, the muscle of exercised patients resembled that of healthy lean individuals. CONCLUSIONS: This study provides compelling evidence-from gene to function-that strongly supports the incorporation of exercise into the recovery algorithm for bariatric patients so as to counteract the post-surgical loss of muscle mass and function.

Adrenal steroidogenesis and ovarian reserve in adult childhood-onset systemic lupus erytematosus patients.

OBJECTIVE: To assess overall adrenal mineralocorticoid/glucocorticoid/androgen steroidogenesis in childhood-onset systemic lupus erythematosus (cSLE) patients and the possible effect of prednisone on adrenal hormones and ovarian reserve. METHODS: Fifty-one adult cSLE (ACR criteria) patients and 23 healthy controls were evaluated for adrenal steroidogenesis including mineralocorticoid (progesterone, deoxycorticosterone, aldosterone), glucocorticoid (17-OHprogesterone, 11-desoxycortisol, cortisol), and androgen (dehydroepiandrosterone-sulfate, androstenedione, total testosterone, and dihydrotestosterone) hormones. Ovarian reserve assessment included follicle-stimulating hormone (FSH), estradiol, anti-Müllerian hormone, ovarian volumes, and antral follicle count. RESULTS: The median of current age [29.11 (19-39.8) vs. 30.8 (19.6-42.1) years, p = 0.502] was similar in adult cSLE and controls. Regarding mineralocorticoid/glucocorticoid, the median of progesterone (p = 0.003), 17-OH progesterone (p < 0.001), and 11-desoxycortisol (p = 0.036) were significantly lower in patients compared to controls. All androgen steroidogenesis hormones were reduced in the former group [dehydroepiandrosterone-sulfate (p < 0.001), androstenedione (p = 0.001), total testosterone (p = 0.005), and dihydrotestosterone (p < 0.001)]. Further comparison of patients with and without current use of prednisone and controls revealed a predominant impact on adrenal glucocorticoid and androgen steroidogenesis with reduced levels of 17-OH progesterone [0.17 (0-0.5) vs. 0.27 (0.1-2.9) vs. 0.33 (0.1-0.8) ng/mL, p < 0.001], dehydroepiandrosterone-sulfate [0.155 (0-0.6) vs. 0.49 (0.1-1.6) vs. 1.11 (0.1-2.6) µg/mL, p < 0.001], androstenedione [0.56 (0.2-4.4) vs. 1.7 (0.5-4.5) vs. 2.33 (0.3-3.8) ng/mL, p < 0.001], total testosterone [12 (12-167) vs. 16 (12-28) vs. (16.5 (0-50) ng/d, p = 0.002], and dihydrotestosterone [92.68 (11.8-198.5) vs. 160.62 (37.9-842.1) vs. 188.3 (71.3-543.9) pg/ml, p < 0.001] in patients under this drug. In addition, patients with this therapy had reduced median ovarian volumes [4.14 (2-12) vs. 7.13 (2-25.7) vs. 5.18 (2.4-17.3) cm3, p = 0.028) that was not associated with cyclophosphamide cumulative dose (p > 0.05). The median prednisone dose was 15/mg/day (2.5-40). CONCLUSIONS: We provided novel evidence that cSLE patients have an overall androgen/glucocorticoid/mineralocorticoid adrenal suppression. Furthermore, low/moderate prednisone use seems to underlie these abnormalities and may also adversely affect ovarian reserve, independently of immunosuppressants. Key Points • cSLE patients have an overall androgen/glucocorticoid/mineralocorticoid adrenal suppression. • Low/moderate prednisone use may affect ovarian reserve, independently of immunosuppressants.

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.

HR-pQCT in vivo imaging of periarticular bone changes in chronic inflammatory diseases: Data from acquisition to impact on treatment indications.

Imaging is essential for the assessment of bone and inflammatory joint diseases. There are several imaging techniques available that differ regarding resolution, radiation exposure, time expending, precision, cost, availability or ability to predict disease progression. High-resolution peripheral quantitative computed tomography (HR-pQCT) that was introduced in 2004 allows the in vivo evaluation of peripheral bone microarchitecture and demonstrated high precision in assessing bone changes in inflammatory musculoskeletal diseases. This review summarizes the use of HR-pQCT for the evaluation of the hand skeleton in inflammatory joint diseases. We conducted a review of the literature regarding the protocols that involve hand joints assessment and evaluation of bone changes as erosions and osteophytes in chronic inflammatory diseases. Apart from measuring bone density and structure of the radius and the tibia, HR-pQCT has contributed to assessment of bone erosions and osteophytes, considered the hallmark of diseases as rheumatoid arthritis and psoriatic arthritis, respectively. In this way, there are some conventions recently established by rheumatic study groups that we just summarized here in order to standardize HR-pQCT measurements.

Increased adiposity by feeding growing rats a high-fat diet results in iron decompartmentalisation.

The present study reports the effects of a high-fat (HF) diet of over 8 weeks on the Fe status of growing rats. Tissue Fe levels were analysed by atomic absorption spectrophotometry, and whole-body adiposity was measured by dual-energy X-ray absorptiometry. Histopathology and morphometry of adipose tissue were performed. Liver homogenates were used for measuring ferroportin-1 protein levels by immunoblotting, and transcript levels were used for Fe genes measured by real-time PCR. Tissue Fe pools were fit to a compartmental biokinetic model in which Fe was assessed using fourteen compartments and twenty-seven transfer constants (kj,i from tissue 'i' to tissue 'j') adapted from the International Commission on Radiological Protection (ICRP) 69. Ten kj,i were calculated from the experimental data using non-linear regression, and seventeen were estimated by allometry according to the formula ${k_{i,j}} = a \times {M^b}$. Validation of the model was carried out by comparing predicted and analysed Fe pool sizes in erythrocytes, the liver and the spleen. Body adiposity was negatively associated with serum Fe levels and positively associated with liver Fe stores. An inferred increase in Fe transfer from bone marrow to the liver paralleled higher hepatic Fe concentrations and ferritin heavy-chain mRNA levels in the HF diet-fed animals, suggesting that liver Fe accumulation occurred at least in part due to a favoured liver erythrocyte uptake. If this feeding condition was to be prolonged, impaired Fe decompartmentalisation may occur, ultimately resulting in dysmetabolic Fe overload.

Changes to Body Composition in Women With Long-Standing Established Rheumatoid Arthritis: Differences by Level of Disease Activity.

INTRODUCTION: Few studies on rheumatoid arthritis have investigated disease activity and body composition by dual-energy X-ray absorptiometry including evaluation of visceral adipose tissue. Thus, we sought to verify the association between body composition by dual-energy X-ray absorptiometry, including visceral adipose tissue, and inflammatory activity in long-standing established rheumatoid arthritis. METHODS: Seventy-eight postmenopausal women with rheumatoid arthritis (American College of Rheumatology 2010) were studied. Disease activity was assessed by composite indexes (DAS28, CDAI, SDAI) and C-reactive protein. Potential association between body composition and disease activity was analysed by Pearson correlation and Tukey´s test (p < 0.05). RESULTS: There was significant negative correlation between C-reactive protein and appendicular lean mass index (r = -0.234, p = 0.039). After adjusting for confounding variables, women with C-reactive protein >10 mg/L had a lower appendicular lean mass index than those with C-reactive protein 5-10 mg/L and <5 mg/L (6.3 ± 0.8 kg/m2 vs 7.2 ± 1.2 kg/m2 vs 6.8 ± 1.0 kg/m2, respectively; p = 0.013). Women with moderate inflammation (C-reactive protein 5-10 mg/L) had more fat than those with C-reactive protein >10 mg/L and C-reactive protein <5 mg/L (12.4 ± 3.5 kg/m2 vs 9.9 ± 3.6 kg/m2 vs 10.5 ± 2.8 kg/m2, respectively; p = 0.040), as well as more visceral adipose tissue than women with higher and lower C-reactive protein (812.5 ± 266.4 cm3 vs 604.3 ± 236.3cm3 vs 658.9 ± 255.6 cm3; p = 0.009). CONCLUSIONS: High inflammatory activity that persists after a long disease duration was associated with both lower muscle and fat mass (including visceral adipose tissue), which is suggestive of more exuberant rheumatoid cachexia. Conversely, moderate activity was associated with greater visceral adipose tissue, which is associated with increased cardiovascular risk. These results point to the existence of different body composition profiles according to inflammatory status and the importance of individualized approaches to muscle mass and adiposity according to disease activity level in long-standing rheumatoid arthritis.

Lower genital tract infections in young female juvenile idiopathic arthritis patients.

BACKGROUND: To evaluate human papillomavirus (HPV), Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections in juvenile idiopathic arthritis (JIA) patients. METHODS: After exclusion, 33 female adolescent and young JIA patients (ILAR criteria) and 28 healthy controls were selected for this study. Demographic data, gynecological, sexual function, cervical cytology and histological abnormalities were evaluated. JIA clinical/laboratorial parameters and treatment were also assessed. HPV-DNA, CT-DNA and NG-DNA testing in cervical specimens were performed by Hybrid Capture 2 assays. RESULTS: The mean current age was similar in JIA patients and controls (23.3 ± 6.24 vs. 26.1 ± 6.03 years, p = 0.09). The frequencies of sexual intercourse (76% vs. 89%, p = 0.201) and abnormal cervical cytology (24% vs. 11%, p = 0.201) were similar in JIA compared to controls. The higher frequency of HPV infection in JIA patients than controls (30% vs. 11%, p = 0.155) did not reach statistical significance. CT (0% vs. 7%, p = 0.207) and NG infections (0% vs. 4%, p = 0.459) were also alike in both groups. Further evaluation of JIA patients with abnormal and normal cervical cytology showed that the former group had a higher frequency of HPV infection (87% vs. 12%, p = 0.0002) with a low frequency of HPV vaccination (0% vs. 8%, p = 1.0). No differences were evidenced between these two JIA groups regarding demographic data, sexual function and clinical/laboratorial parameters. The frequencies of methotrexate (p = 0.206) and biological agent use (p = 0.238) were similar in both JIA groups. CONCLUSIONS: To our knowledge, this was the first study to assess lower genital infections in JIA patients allowing the identification of HPV as main cause of cervical dysplasia. Methotrexate and biological agents do not seem to increase risk of lower genital tract infections in JIA patients.

Ovarian reserve in young juvenile idiopathic arthritis patients.

OBJECTIVES: Juvenile idiopathic arthritis (JIA) occurs during reproductive age, however, there are no systematic data regarding ovarian function in this disease. METHODS: Twenty-eight post-pubertal JIA patients and age-matched 28 healthy controls were studied. Complete ovarian function was assessed during the early follicular phase of the menstrual cycle including anti-Müllerian hormone (AMH), estradiol, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and antral follicle count (AFC) by ovarian ultrasound, and anti-corpus lutheum antibodies (anti-CoL). Demographic data, menstrual abnormalities, disease parameters and treatment were also evaluated. RESULTS: The mean current age (22.6 ± 6.59 vs. 22.5 ± 6.59 years, p = .952) was similar in JIA patients and healthy controls with a higher median menarche age [13(8-16) vs. 12(8-14) years, p = .029]. A lower median AMH levels [2.65(0.47-9.08) vs. 4.83(0.74-17.24) ng/mL, p = .029] with a higher LH [8.44 ± 4.14 vs. 6.03 ± 2.80 IU/L, p = .014] and estradiol levels [52.3(25.8-227.4) vs. 38.9(26.2-133.6) pg/mL, p = .008] were observed in JIA compared to control group. Anti-CoL and AFC were similar in both groups (p > .05). Further analysis of JIA patients revealed that current age, disease duration, number of active/limited joints, ESR, CRP, patient/physician VAS, JADAS 71, DAS 28, CHAQ, HAQ, patient/parents PedsQL, PF-SF 36, cumulative glucocorticoid and cumulative methotrexate doses were not correlated with AMH, FSH, estradiol levels or AFC (p > .05). CONCLUSION: The present study was the first to suggest diminished ovarian reserve, not associated to hypothalamic pituitary gonadal axis, in JIA patients during reproductive age. The impact of this dysfunction in future fertility of these patients needs to be evaluated in prospective studies.

Lower genital tract infections in young female juvenile idiopathic arthritis patients

Abstract Background: To evaluate human papillomavirus (HPV), Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections in juvenile idiopathic arthritis (JIA) patients. Methods: After exclusion, 33 female adolescent and young JIA patients (ILAR criteria) and 28 healthy controls were selected for this study. Demographic data, gynecological, sexual function, cervical cytology and histological abnormalities were evaluated. JIA clinical/laboratorial parameters and treatment were also assessed. HPV-DNA, CT-DNA and NG-DNA testing in cervical specimens were performed by Hybrid Capture 2 assays. Results: The mean current age was similar in JIA patients and controls (23.3 ± 6.24 vs. 26.1 ± 6.03 years, p = 0.09). The frequencies of sexual intercourse (76% vs. 89%, p = 0.201) and abnormal cervical cytology (24% vs. 11%, p = 0.201) were similar in JIA compared to controls. The higher frequency of HPV infection in JIA patients than controls (30% vs. 11%, p = 0.155) did not reach statistical significance. CT (0% vs. 7%, p = 0.207) and NG infections (0% vs. 4%, p = 0.459) were also alike in both groups. Further evaluation of JIA patients with abnormal and normal cervical cytology showed that the former group had a higher frequency of HPV infection (87% vs. 12%, p = 0.0002) with a low frequency of HPV vaccination (0% vs. 8%, p = 1.0). No differences were evidenced between these two JIA groups regarding demographic data, sexual function and clinical/laboratorial parameters. The frequencies of methotrexate (p =0.206) and biological agent use (p =0.238) were similar in both JIA groups. Conclusions: To our knowledge, this was the first study to assess lower genital infections in JIA patients allowing the identification of HPV as main cause of cervical dysplasia. Methotrexate and biological agents do not seem to increase risk of lower genital tract infections in JIA patients.