The −675 4G/5G PAI-1 polymorphism confers genetic susceptibility to systemic lupus erythematosus,its clinical manifestations,and comorbidities in Mexican-Mestizo population

Abstract

Systemic lupus erythematosus (SLE) involves a broad range of factors that contribute to the development of the disease and its comorbidities. Genetic predisposition influences the development of SLE, and the ?675 4G/5G PAI-1 polymorphism has been associated with several pathologies with a chronic inflammatory component. Our objective was to investigate the genetic association between the ?675 4G/5G PAI-1 polymorphism with SLE, its clinical manifestations, and comorbidities in a Mexican-Mestizo population. The ?675 PAI-1 polymorphism was determined by PCR-RFLP in 716 subjects: 293 SLE patients and 423 control subjects. Significant associations for SLE genetic susceptibility were found in carriers of 4G/5G (OR = 2.63; CI 1.81–3.87; p?<?.001) and 4G/4G (OR = 2.70; CI 1.62–4.51; p?<?.001) genotype in comparison with the 5G/5G genotype; 4G allele carriers also presented genetic risk for SLE (OR = 1.63; CI 1.31–2.03; p?<?.001) compared to the 5G allele. Following a dominant genetic model, a similar association was found with the 4G allele to SLE (OR = 2.66; CI1.84–3.84; p?<?.001). The 4G/5G genotype was associated with shorter disease duration (p?=?.039), as well as lower levels of haemoglobin (p?=?.001) and haematocrit (p?=?.009); the need for prednisone treatment (p?=?.001), higher BMI (p?=?.03), presence of type 2?DM (p?=?.015), clinical activity (Mex-SLEDAI = 57%; p?=?.047), Chronicity (SLICC-ACR = 0; p?=?.015) and CRP levels (p?=?.015) were associated with 5G/5G genotypes. In conclusion, the ?675 4G/5G and 4G/4G PAI-1genotypes were found as genetic risk markers of susceptibility for SLE in the Mexican-Mestizo population, and each genotype could influence the clinical manifestations and comorbidities differently in SLE.     

Peripheral whole blood FOXP3 TSDR methylation: a potential marker in severity assessment of autoimmune diseases and chronic infections

Immune dysregulation is a cardinal feature of autoimmune diseases and chronic microbial infections. In particular, regulatory T cells are downregulated in autoimmune diseases while upregulated in chronic microbial infections. FOXP3 is the master regulator of Treg development. Treg-specific demethylated region (TSDR) is a highly conserved locus on the FOXP3 gene that is fully demethylated in natural Tregs but methylated in effector T cells. In our study, we used high resolution melt-polymerase chain reaction (HRM-PCR) to determine the FOXP3 TSDR methylation status in autoimmune diseases and chronic microbial infections. We found that FOXP3 TSDR to have the highest mean melting temperature (highly methylated) in active SLE patients compared to all the other groups (p?<?0.001). The psoriasis group also had a significantly high mean melting temperature (78.62?±?0.20) when compared with the inactive SLE group (78.49?±?0.29, p?<?0.05) and control group (78.44?±?0.25, p?<?0.01). There was no significant difference in melting temperature between inactive SLE and healthy controls. Disease activity in SLE was directly associated with methylation of the FOXP3 TSDR. On the other hand, patients with chronic microbial infections had significantly lower FOXP3 TSDR mean melting temperature (demethylated) when compared with healthy controls (78.28?±?0.21 vs 78.44?±?0.25, p?<?0.05). Our results suggest that the use of HRM-PCR to detect FOXP3 TSDR methylation status is a reliable and easy method to predict natural regulatory T cell levels in peripheral blood in different disease conditions. Determining FOXP3 TSDR methylation status can be a useful tool in diagnosis, and monitoring the severity of autoimmune diseases and chronic microbial infections.     

Application of low dose of FK506 in pancreas transplantation model in Wistar-SD rats

Objective: To probe into application of low dose of FK506(Tacrolimus) in pancreas transplantation.

Methods: Effects of low-dose FK506 (Tacrolimus) in pancreas transplantation with examination of ELISA Electron microscopy and TUNEL by method of random control were studied.

Results: Blood glucose concentration in control group is higher than that in treated group A (FK506) and treated group B (CsA) 7 days after transplantation (p?<?0.05). Serum C-peptide and insulin concentrations in control group are less than that in treated group A (FK506) and treated group B (CsA) 7 days after transplantation (p?<?0.05). Blood glucose, serum C-peptide and insulin concentrations are same as that in control group, group A (FK506) and group B (CsA) (p?>?0.05).There are more apoptotic nuclei in control group than that in treated group A (FK506) and treated group B (CsA) (p?<?0.05). There is no significant difference between group A (FK506) and treated group B (CsA) in sum of apoptotic nuclei (p?>?0.05). There is no significant difference among treated group A (FK506) and treated group B (CsA) in electron microscopy fields.

Conclusion: Low-dose FK506 applied in pancreas transplantation could not only be effective for immunosuppressive, but also be safe for islet cells of pancreas.     

Thymosin α1 plus routine treatment inhibit inflammatory reaction and improve the quality of life in AECOPD patients

Abstract

Context: Thymosin α1 (Tα1) is considered to be a promising immunomodulatory drug and could balance immunity and tolerance in immune tolerance and autoimmunity.

Objective: To explore the efficacy of Tα1 plus routine complex treatment in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD).

Methods: Eighty-four AECOPD patients were enrolled and randomized into an experimental group and a control group. All patients received the routine treatment. Additionally, the experimental group received subcutaneous injections of Tα1 while the control group received placebo. Four weeks later, the curative effect of treatment and immune function of both groups were analyzed.

Results: Partial pressures of oxygen (PaO₂), PaCO₂, and pulmonary function of the experimental group improved after treatment compared to that recorded prior to treatment and that observed for the control group (p?<?0.01, both). The CD4⁺ T cell count, serum interferon (IFN)-γ levels, and the ratios of CD4⁺/CD8⁺ and IFN-γ/interleukin (IL)-4 increased in both groups (p?<?0.01), while the CD8⁺ T cell count and levels of IL-4, IL-8, and leukotrienes B4 (LTB4) decreased as expected (p?<?0.01). Meanwhile, the above-mentioned indices of the experimental group improved significantly compared to the indices of the control group (p?<?0.05 or 0.01).

Conclusions: Tα1 plus routine treatment could improve the immune function of AECOPD patients and inhibit the inflammatory reaction, thus reducing the recurrence of chronic obstructive pulmonary disease (COPD).     

Hyperferritinemia is Associated with Serologic Antiphospholipid Syndrome in SLE Patients

Ferritin may play a direct role on the immune system. We sought to determine if elevated levels of ferritin in lupus patients correlate with disease activity and organ involvement in a large cohort. Ferritin levels (gender and age adjusted) were assessed in 274 lupus serum samples utilizing the LIASON Ferritin automated immunoassay method. Significant disease activity was determined if European Consensus Lupus Activity Index (ECLAM)?>?2 or Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)?>?4. Utilizing an EXCEL database, we compared elevated ferritin levels to manifestations grouped by organ involvement, serology, and previous therapy. The patients were predominantly female (89%), median age was 37 years old, and disease duration was 10.6?±?7.7 years. Hyperferritinemia was found in 18.6% of SLE patients. Compared to subjects with normal ferritin levels, a significantly greater proportion of patients with hyperferritinemia had thrombocytopenia (15.4% vs. 33.3%, p?=?0.003) and lupus anticoagulant (11.3% vs. 29.0%, p?=?0.01). Additionally, compared to normoferritinemic subjects, hyperferritinemic subjects had significantly higher total aCL (99.7?±?369 vs. 30.9?±?17.3 GPI, p?=?0.02) and aCL IgM antibody levels (75.3?±?357.4 vs. 9.3?±?10.3 GPI, p?=?0.02), and marginally lower aCL IgG antibody levels (9.2?±?4.9 vs. 9.7?±?3.9 GPI, p?=?0.096). While the ECLAM score significantly correlated with hyperferritinemia (p?=?0.04), the SLEDAI score was marginally associated with hyperferritinemia (p?=?0.1). Serositis was marginally associated with hyperferritinemia, but not with other manifestations. An association with serologic APS was encountered. Hyperferritinemia was associated with thrombocytopenia, lupus anticoagulant, and anti-cardiolipin antibodies suggest that it may be an early marker for secondary antiphospholipid syndrome in SLE patients.     

FcγRIIa and FcγRIIIb polymorphisms and associations with clinical manifestations in systemic lupus erythematosus patients

Abstract

In this study, we aimed to investigate whether the distribution of the FcγRIIa and FcγRIIIb polymorphisms determines susceptibility to systemic lupus erythematosus (SLE) and acts as predictors of SLE clinical manifestations in the Brazilian patients. A total of 157 patients that fulfilled the American College of Rheumatology classification criteria for SLE and 160 healthy volunteers were included in this study. FCGR2A and FCGR3B genotypes were determined by polymerase chain reaction-based allotyping methods with allele-specific primers; the clinical features were obtained from the patients' official medical records. In the case of FcγRIIa polymorphism, it was observed association of the allele FCGR2A-R-131 (p?=?0.02, odds ratio (OR)=1.44) and genotype RR-131 (p?=?0.03, OR?=?2.09) with SLE. These associations were higher with allele (p?<?0.01, OR?=?1.67) as well genotype (p?=?0.01, OR?=?2.85) when lupus nephritis was considered. In contrast, the allele FCGR2A-H-131 was associated with susceptibility to arthritis and anti-DNA antibodies (p?=?0.05 for both). As for FcγRIIIb polymorphism, skewing did not differ significantly between patients and controls, however the genotype FCGR3B*02*02 was associated with susceptibility to arthritis (p?=?0.02) and malar rash (p?=?0.03), but no association with nephritis was found. The results demonstrate that FcγRIIa polymorphism is associated with susceptibility to SLE in Brazilian patients, whereas for FcγRIIIb polymorphism no association was found. However, notably, both polymorphisms present allelic variants that influence the clinical manifestations and may contribute to the pathogenesis of the disease. In addition, to our knowledge, this is the first study considering the frequency of FcγRIIIb polymorphism in Brazilian SLE patients.     

Computerized acoustic cardiography correlates with echocardiography and invasive haemodynamics after percutaneous transvenous mitral commissurotomy

Background:?Rheumatic mitral stenosis severity has been assessed by the systolic time interval between the QRS onset and the first heart sound (QS1) by phonocardiography. We hypothesized that non-invasive computerized acoustic cardiography could evaluate mitral stenosis severity compared with echocardiography and invasive haemodynamics in patients undergoing percutaneous transvenous mitral commissurotomy (PTMC).

Methods:?27 patients underwent computerized acoustic cardiography, echocardiography, and invasive haemodynamic measurements prior to and after PTMC.

Results:?The mean age was 31?±?10 years, and 21 (78%) were female. By echocardiography, mitral valve area increased from 0.82?±?0.14 to 1.50?±?0.24 cm² (p?<?0.0001). The QS1 interval decreased from 101.7?±?12.9 to 93.2?±?9.2?ms (p?<?0.0001). The change in the QS1 interval correlated with the change in mitral valve area by echocardiography (p?=?0.037), right ventricular systolic pressure (p?<?0.0001), and the invasive mitral valve gradient (p?=?0.076).

Conclusions:?Acoustic cardiography may be used as an adjunctive non-invasive diagnostic tool to assess mitral stenosis severity.     

Serum Leptin Levels,Leptin Receptor Gene (LEPR) Polymorphism,and the Risk of Systemic Lupus Erythematosus in Kashmiri Population

The study is conducted to evaluate relationship between LEPRQ223R (Gln?>?Arg) polymorphism, serum leptin levels, soluble leptin receptor (SOb-R) levels and SLE risk in Kashmiri population.LEPR genotyping was done by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in 100 unrelated SLE patients and equal number of healthy control subjects. Leptin and SOb-R levels were measured by ELISA assays. The present study showed higher frequency of variant genotype (AG?+?GG) in cases compared to controls [OR?=?2.52, CI?=?1.18–5.35, p?=?0.03]. Moreover the rare (G) allele was significantly more predominant in cases than controls [OR?=?1.49, p?=?0.04]. Interestingly a positive association between the variant genotype and the development of arthritis [OR?=?11.8, CI?=?1.6–85.1, p?=?0.002] and an inverse association with cardiac disorder [OR?=?0.09, CI?=?0.02–0.46, p?=?0.001] was observed in this study. Furthermore the study showed significant differences of leptin levels in SLE patients and controls (23.9?±?19.5 vs 14.8?±?10.4, p?<?0.001). SLE patients in the highest quartile leptin levels (≥32.5?ng/mL) were significantly more likely to have higher BMI (p?=?0.001) and increased risk of developing arthritis (p?=?0.02). Furthermore positive association was observed between the variant genotype(AG?+?GG) and leptin levels (p?=?0.001) in SLE patients. Thus, it is evident from our study that LEPRQ223R polymorphism and elevated leptin levels are associated with increased susceptibility of SLE in Kashmiri population.     

Correlation of plasma and urine Wnt5A with the disease activity and cutaneous lesion severity in patients with systemic lupus erythematosus

Reliable noninvasive biomarkers are needed to accurately assess disease activity and prognosis in patients with systemic lupus erythematosus (SLE). The purpose of this study was to investigate the clinical relevance of Wnt5A with disease activity and severity with cutaneous involvement in particular in SLE patients; its concentrations in plasma and urine were examined and analyzed. In the cross-sectional study, the clinical relevance of Wnt5A protein was evaluated in both plasma and urine of SLE patients and healthy cohorts using commercial enzyme-linked immunosorbent assays (ELISA). Significantly, more abundances of Wnt5A protein were determined in both of plasmas and urines of SLE patients compared to healthy cohorts (p < 0.0001), which were even higher in active disease (AD) SLE patients relative to low disease activity (LDA) SLE patients (p < 0.0001). Meanwhile, the ROC curve analysis demonstrated that the plasma and urine Wnt5A were potential candidate biomarkers for identifying the disease activity and severity in SLE patients. The discriminant function analysis further revealed that the plasma and urine Wnt5A were separated and distinct for AD SLE patients and healthy controls. In consistence, the disease severity was correlated with the plasma and urine Wnt5A as ascertained by CLASI activity score and the prevalence of serositis in SLE patients. These results suggest that Wnt5A, as a summary measure for different inflammatory processes, could be a potential biomarker for accessing the disease activity, and a noninvasive biomarker for evaluating the disease severity in terms of cutaneous involvement in SLE patients.

     

A multi-level analysis of individual- and school-level correlates of physical fitness in children

Background: Children’s physical fitness is potentially influenced by biological, behavioural and environmental factors.

Aim: To investigate the importance of individual-level and school-level characteristics in explaining variation in children’s physical fitness.

Subjects and methods: The sample comprised 354 Portuguese children, aged 5–10?years. Physical fitness [(handgrip (HG) strength, standing long jump (SLJ), shuttle-run (SR), total physical fitness score (PFz)], gross motor coordination (GMC) and body mass index (BMI) were assessed. Moderate-to-vigorous physical activity (MVPA) was objectively monitored; birth weight and socio-economic status (SES) were obtained by questionnaire. School contexts were assessed via an objective audit. Multilevel models using the Bayesian approach were used.

Results: Age was positively associated with HG, SLJ and PFz (p?<?0.05); BMI was positively associated with HG (p?<?0.05) and GMC with all physical fitness components (p?<?0.05); MVPA was only associated with PFz (p?<?0.05); children with level A SES outperformed those with level C SES in HG (p?<?0.05), but those with level B SES outperformed their level A SES peers in SR (p?<?0.05). Within the school context, no equipment for physical education was negatively associated with HG (p?<?0.05).

Conclusion: In the primary school years, individual-level characteristics were more important than the school context in explaining variations in physical fitness.     

Evaluation of the optimum time for direct application of fibroblast growth factor to human traumatic tympanic membrane perforations

Abstract

Objective: The aim of this study was to determine the optimum time for direct application of basic fibroblast growth factor (bFGF) on large traumatic tympanic membrane perforations (TMPs). Study design: Prospective clinical study. Setting: Tertiary University Hospital. Methods: Ninety-three patients, with traumatic TMPs greater in extent than 25% of the entire tympanic membrane, were randomized into observation and bFGF-treated groups (～0.2–0.25?mL of bFGF solution was applied directly onto the TM once daily and continued until the perforation closed). Initial visit times were subcategorized into perforation durations of ≤3 and >3 days, thereby rendering two subgroups, as follows: A and B in the observation group; and C and D in the bFGF-treated group. The closure rate and mean closure time were evaluated after 6 months. Results: Eighty-six patients were finally analyzed. After 6 months, the bFGF-treated group exhibited a significantly higher total closure rate (97.8 versus 82.5%, p?<?0.05) and a shorter mean closure time (12.5?±?3.4 versus 34.0?±?5.9 days, p?<?0.05) compared with the spontaneous healing group. In addition, in the observation group, visiting time was not associated with differences in closure rate (p?>?0.05) and mean closure time (p?>?0.05), between the A and B subgroups. Similarly, in the bFGF-treated group, visiting time was not associated with differences in closure rate (p?>?0.05) between the C and D subgroups. However, the D subgroup was characterized by significantly shortened mean closure time compared with the C subgroup (p?<?0.05). Conclusions: This study shows the beneficial effect of bFGF on human traumatic large TMPs when applied after the 3rd day post-injury had passed (i.e. during the proliferative stage of wound healing). The procedure can not only significantly shorten closure time but can also reduce both the clinical administration duration and occurrence of side-effects associated with bFGF.     

Anti-cyclic Citrullinated Peptide Antibodies are Highly Associated with Severe Bone Lesions in Rheumatoid Arthritis Anti-CCP and Bone Damage in RA

In the present study we investigated the predictive value of anti-cyclic citrullinated peptide antibodies (anti-CCP) in early rheumatoid arthritis (RA) with respect to the bone damage.

Fifty-four patients with early RA (onset <12 months), 35 classified as established RA (onset >12 months), 33 healthy donors and 76 non-RA autoimmune diseases, were enrolled. Anti-CCP and IgG, IgA, IgM rheumatoid factors (RFs) were determined at baseline. Disease activity score (DAS 28) was calculated at the entry. Bone involvement was evaluated by X-rays and sonography.

The specificity of anti-CCP was 98.4%; significantly (?p<0.01) higher than those of the IgM- (86.0%), IgA- (86.0%) and IgG-RFs (66.2%), respectively. Anti-CCP were detected in 23/54 (42.6%) early RA patients and in 16/35 (45.7%) established RA patients. In the early RA group, 6/33 (18.2%) of the patients without bone lesions, 12/16 (75%) with juxta-articular osteoporosis (JO) and 5/5 with joint erosions (JE) resulted positive showing a significant (?p<0.001) difference between the groups without and with radiological damage.

In the established RA group a significant (?p<0.01) difference being between the group without radiological damage and that with JE was found. Finally, in patients without radiological lesions, examined by ultrasound, anti-CCP antibodies were detected only in subjects with pathologic findings (31.25%).

Data here reported confirm that the presence of anti-CCP are specific for diagnosis of RA, of recent onset also and they are potentially useful as prognostic index of bone involvement.     

Serum Growth Arrest-Specific Protein 6 Levels are a Reliable Biomarker of Disease Activity in Systemic Lupus Erythematosus

Purpose

Growth arrest-specific protein 6 (Gas6) has been suggested to be a biomarker of disease activity in patients with systemic lupus erthematosus (SLE). We investigated the clinical significance of this protein in Korean SLE.

Methods

Blood samples were collected from 150 SLE patients and 50 normal controls (NC). In addition, follow-up samples were collected from 50 SLE patients.

Results

Serum Gas6 levels of SLE patients (43.01?±?28.02 ng/mL) were higher than those of NC (20.15?±?9.23 ng/mL, p?<?0.001). When evaluated sensitivity and specificity of the Gas6 for diagnosing SLE using ROC curves, the sensitivity and specificity were 72.7 % and 84 % with a cut-off value of 25.3 ng/mL. In the ROC analysis of Gas6, anti-dsDNA antibody, ESR, complement 3 and complement 4 to identify patients with active lupus, area under the curve (AUC) of Gas6 was highest with 0.763. Serum Gas6 levels were significantly higher in the patients with serositis (70.04?±?30.85 ng/mL) and renal disorder (65.66 ±32.28 ng/mL) compared to those without (41.88?±?27.44 ng/mL, p?=?0.033, 40.3?±?26.33 ng/mL, p?=?0.001, respectively). Gas6 levels were correlated positively with anti-dsDNA antibody (r?=?0.199, p?=?0.015), ESR (r?=?0.204, p?=?0.013) and SLEDAI (r?=?0.512, p?<?0.001). In addition, serum Gas6 levels were correlated negatively with hemoglobin (r?=??0.165, p?=?0.043), lymphocyte count (r?=??0.165, p?=?0.043), complement 3 (r?=??0.343, p?<?0.001) and complement 4 (r?=??0.316, p?<?0.001). Furthermore, change in serum Gas6 levels was correlated with change in SLEDAI levels in the SLE patients that were followed up (r?=?0.524, p?<?0.001).

Conclusion

These results suggest that serum Gas6 can be a reliable clinical marker for monitoring disease activity and treatment response in SLE.     

Associations between interleukin-23R and interleukin-12B polymorphisms and psoriasis susceptibility: a meta-analysis

Objective: The aim of this study was to determine whether interleukin (IL)-23?R and IL-12B polymorphisms confer susceptibility to psoriasis.

Methods: The authors conducted a meta-analysis on associations between the IL-23?R and IL-12B polymorphisms and psoriasis susceptibility.

Results: A total of 14 comparison studies were included in this meta-analysis. The meta-analysis identified a significant association between psoriasis and 2 alleles of the rs11209026 and rs7530511 polymorphisms in Europeans (odds ratio [OR]?=?0.624, 95% confidence interval [CI]?=?0.565–0.697, p?<?1.0?×?10^?8; OR?=?0.804, 95% CI?=?0.743–0.869, p?=?3.0?×?10^?7, respectively). Meta-analysis of IL-12B showed a significant association between the 2 alleles of the rs6887695 and rs3212227 polymorphisms and the risk of developing psoriasis (OR?=?0.710, 95% CI?=?0.673–0.749, p?<?1.0?×?10^?8; OR?=?0.684, 95% CI?=?0.639–0.731, p?<?1.0?×?10^?8, respectively). Stratification by ethnicity identified an association between the rs6887695 and rs3212227 polymorphisms and psoriasis in Europeans.

Conclusions: This meta-analysis showed that the IL-23?R (rs11209026 and rs7530511) polymorphisms are associated with psoriasis risk in Europeans and that the IL-12B (rs6887695 and rs3212227) polymorphisms are associated with susceptibility to psoriasis in Europeans.     

A new oligonucleotide-based ELISA for the detection of anti-double-stranded DNA antibodies

The detection and measurement of antibodies to double-stranded (ds) DNA is important in the diagnosis and monitoring of patients with systemic lupus erythematosus (SLE). Several methods are available for their determination but none of them is completely satisfactory. Usually, purified dsDNA from different sources is used as antigen in the solid (enzyme-linked immunosorbent assay, ELISA) or liquid phase (Farr assay). Alternatively, anti-dsDNA antibodies can be demonstrated by immunofluorescence, using the haemoflagellate Crithidia luciliae (CLIFT).

We have developed a new oligonucleotide-based anti-dsDNA ELISA in which dsDNA, constituted of a 5′photobiotinylated nucleic acid probe and its highly specific complementary oligonucleotide, is formed onto the solid-phase. To do that, a 40 bp probe is coated on the microplate wells via streptavidin–biotin bond and the in vitro (in solid-phase) developed hybrid between probe and its complementary helix used as capturing antigen. The assay has proved to be specific and the several experiments performed to ascertain the absence of single-stranded DNA (ssDNA) contamination and/or non specific binding to plastic, streptavidin, probe (without complementary chain) have all excluded any significant interference.

To evaluate the clinical performance of this new assay, 114 serum samples from 68 SLE patients and 85 samples from 85 disease controls, in addition to 30 blood donors, were studied. The results were compared with commercial ELISAs, Farr assay and indirect immunofluorescence.

The sensitivity and specificity were 66.2 and 96.4%, respectively, comparable and even better than those of the commercially available anti-dsDNA kits. Anti-dsDNA antibody levels, measured with the oligonucleotide–ELISA, correlated with SLE clinical activity determined using the European Consensus Lupus Activity Measurement (ECLAM) (r = 0.59, p < 0.0001).

In conclusion, this assay has proved to be reproducible, and the results correlate well with other standard anti-dsDNA assays. The features of this new assay make it promising for clinical use.     

Effect of hydroxychloroquine pre-exposure on infection with SARS-CoV-2 in rheumatic disease patients: a population-based cohort study

ObjectivesEarly in vitro studies have suggested that hydroxychloroquine (HCQ) is a potentially useful drug against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. This study was conducted to determine whether HCQ had a preventive effect on coronavirus disease 2019 (COVID-19) in rheumatic disease patients who were taking HCQ.MethodsWe conducted a population-based retrospective cohort study using the records of the Korean Health Insurance Review and Assessment (HIRA) claim records. The clinical data of patients with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) who were tested for SARS-CoV-2 were investigated. We compared the attack rate of COVID-19 between those who underwent HCQ therapy within 14 days before the test for SARS-CoV-2 (HCQ users) and HCQ non-users. Data were analysed using logistic regression models, χ², and Student's t-tests.ResultsAs of 15th May 2020, 2066 patients with RA or SLE were tested for COVID-19. Among them, 31.4% (649/2066) were treated with HCQ. Most HCQ users (93.7%, 608/649) were taking 200–400 mg/day recommended for the treatment of rheumatic diseases. The attack rate of COVID-19 in the HCQ users (2.3%, 15/649) did not differ from that in the HCQ non-users (2.2%, 31/1417) (p 0.86).ConclusionsHCQ prophylactic use at a usual dose did not prevent COVID-19 in patients with rheumatic disease.     

Atopy in children with systemic onset juvenile idiopathic arthritis (SoJIA) is associated with a worse outcome

Context: Atopy and systemic onset juvenile idiopathic arthritis (SoJIA) are two potential outcomes of a dysregulated immune system. Although rare, SoJIA causes 60% of the morbidity of JIA patients which exhibit a wide heterogeneity of prognosis and treatment. Co-morbidities can complicate the responses to therapy.

Objective: To study the influence of co-existing atopy on the prognosis of SoJIA.

Materials and Methods: Patients diagnosed with SoJIA between Jan 2006 and Sep 2010 were screened, enrolled in this prospective cohort study, and followed for 2 years. Management of SoJIA patients was assessed by ACR Pedi30/50/70 criteria, laboratory variables, and systemic feature score.

Results: At disease onset, 61 SoJIA patients (34 male and 27 female) were enrolled and were divided into SoJIA patients with atopy (n?=?27) or those without atopy (n?=?34). Atopic group at disease onset had significantly higher numbers of affected joints, ferritin levels and IgE serum levels than the non-atopic group. At 3 and 6 months, fewer SoJIA patients with atopy reached the ACR Pedi50 criteria (p?(p?Conclusion: Atopy may exert an adverse influence on SoJIA, as patients with atopy had a more active disease at diagnosis and poorer outcome. This prospective study showed that the TH1/TH2 hypothesis was too simplistic to explain the interaction between atopy and SoJIA.     

Obesity,hypertension, social determinants of health and the epidemiologic transition among traditional Amazonian populations

Abstract

Background: The health and nutritional situation of adults from three rural vulnerable Amazonian populations are investigated in relation to the Social Determinants of Health (SDH) and the epidemiologic transition.

Aim: To investigate the role of the environment and the SDH on the occurrence of chronic-degenerative diseases in these groups.

Subjects and methods: Anthropometric, blood pressure and demographic data were collected in adults from the RDS Mamirauá, AM (n?=?149), Flona Caxiuanã, PA (n?=?148) and quilombolas, PA (n?=?351), populations living in a variety of socio-ecological environments in the Brazilian Amazon.

Results: Adjusting for the effect of age, quilombola men are taller (F?=?9.85; p?<?0.001) and quilombola women present with higher adiposity (F?=?20.43; p?<?0.001) and are more overweight/obese. Men from Mamirauá present higher adiposity (F?=?9.58; p?<?0.001). Mamirauá women are taller (F?=?5.55; p?<?0.01) and have higher values of waist circumference and subscapular/triceps index. Quilombolas present higher prevalence of hypertension in both sexes and there are significant differences in rates of hypertension among the women (χ² = 17.45; p?<?0.01). The quilombolas are more dependent on government programmes, people from Mamirauá have more economic resources and the group from Caxiunã have the lowest SES.

Conclusion: In these populations, the SDH play a key role in the ontogeny of diseases and the ‘diseases of modernity’ occur simultaneously with the always present infectoparasitic pathologies, substantially increasing social vulnerability.