Time to diagnosis in systemic lupus erythematosus: Associated factors and its impact on damage accrual and mortality. Data from a multi-ethnic, multinational Latin American lupus cohort.

BACKGROUND: Systemic lupus erythematosus (SLE) often mimics symptoms of other diseases, and the interval between symptom onset and diagnosis may be long in some of these patients. Aims: To describe the characteristics associated with the time to SLE diagnosis and its impact on damage accrual and mortality in patients with SLE from a Latin American inception cohort. METHODS: Patients were from a multi-ethnic, multi-national Latin-American SLE inception cohort. All participating centers had specialized lupus clinics. Socio-demographic, clinical/laboratory, disease activity, damage, and mortality between those with a longer and a shorter time to diagnosis were compared using descriptive statistical tests. Multivariable Cox regression models with damage accrual and mortality as the end points were performed, adjusting for age at SLE diagnosis, gender, ethnicity, level of education, and highest dose of prednisone for damage accrual, plus highest dose of prednisone, baseline SLEDAI, and baseline SDI for mortality. RESULTS: Of the 1437 included in these analyses, the median time to diagnosis was 6.0 months (Q1-Q3 2.4-16.2); in 721 (50.2%) the time to diagnosis was longer than 6 months. Patients whose diagnosis took longer than 6 months were more frequently female, older at diagnosis, of Mestizo ethnicity, not having medical insurance, and having "non-classic" SLE symptoms. Longer time to diagnosis had no impact on either damage accrual (HR 1.09, 95% CI 0.93-1.28, p = 0.300) or mortality (HR 1.37, 95% CI 0.88-2.12, p = 0.200). CONCLUSIONS: In this inception cohort, a maximum time of 24 months with a median of 6 months to SLE diagnosis had no apparent negative impact on disease outcomes (damage accrual and mortality).

Expression and clinical implications of HLA-G and PD-L1 following kidney transplantation: A cohort study.

Kidney transplantation (KT) is the preferred treatment for end-stage renal diseases. Human leukocyte antigen G (HLA-G) and programmed death-ligand 1 (PD-L1) have notable clinical and therapeutic significance in transplantation because of their roles in promoting tolerance. This study aimed to assess HLA-G and PD-L1 levels at various stages following KT. A cohort of 12 patients was monitored from the pretransplant phase to 12 months post-surgery. Blood samples were taken at specific intervals: before kidney transplantation (T0), and then on the 7th (T7), 30th (T30), 90th (T90), 180th (T180), and 365th days post transplantation. Renal biopsies were performed in patients with graft dysfunction. Plasma levels of soluble HLA-G (sHLA-G) and PD-L1 were quantified using enzyme-linked immunosorbent assays. Additionally, immunohistochemistry was used to detect the presence of both molecules in biopsy samples. Multivariate analysis indicated that episodes of rejection were correlated with decreased expression of sHLA-G (P < .001) and PD-L1 (P < .001). Over the course of the study, the sHLA-G levels also declined (P < .001). Patients who had been transfused had lower PD-L1 levels (P = .03). Furthermore, kidney recipients from related live donors had increased HLA-G expression (P < .001). Our findings suggest that diminished HLA-G and PD-L1 levels correlate with an increased risk of graft rejection. Notably, HLA-G expression significantly decrease after the third-month posttransplantation.

MODIFIED MUBARAK TECHNIQUE FOR FLEXIBLE FLATFOOT CORRECTION IN CHILDREN AND ADOLESCENTS.

Objective: To describe the technique, analyze possible radiographic correction and evaluate the clinical result of medial and plantar calcaneal displacement osteotomy associated with opening wedge cuboid osteotomy for flexible flatfoot correction. Methods: 23 patients (30 feet) diagnosed with flexible flat foot treated with plantar and medial calcaneal displacement osteotomy associated with opening wedge cuboid osteotomy were evaluated retrospectively. In the lateral radiographs calcaneal pitch and Meary's angle were the radiographic parameters evaluated; while the talonavicular coverage angle was evaluated in the anteroposterior radiographs. To assess the clinical outcome of the surgical procedure, the American Orthopedic Foot and Ankle Society Score (AOFAS) for the ankle and hindfoot was adopted. Results: The mean values of the evaluated angles and AOFAS score for ankle and hindfoot significantly improved when comparing pre- and postoperative values. Conclusion: Plantar and medial calcaneal displacement osteotomy associated with an opening wedge cuboid osteotomy is able to improve radiological and clinical parameters of child patients with flexible flatfoot. Level of Evidence III, Retrospective Comparative Study.

Objetivo: Descrever a técnica, analisar possíveis correções radiográficas e avaliar o resultado clínico da osteotomia de deslocamento medial e plantar do calcâneo associada à osteotomia em cunha de adição do cuboide para correção do pé plano flexível de crianças. Métodos: Foram avaliados retrospectivamente 23 pacientes (30 pés) com diagnóstico de pé plano flexível tratadas com osteotomia de deslocamento plantar e medial do calcâneo associada à osteotomia em cunha de adição do cuboide. Os parâmetros radiográficos avaliados nas imagens em perfil foram o pitch do calcâneo e o ângulo de Meary, enquanto nas radiografias anteroposteriores o ângulo de cobertura do tálus. Para avaliar o resultado clínico do procedimento cirúrgico, foi adotado o escore da American Orthopaedic Foot and Ankle Society (AOFAS) para tornozelo e retropé. Resultados: Os valores médios dos ângulos avaliados e do escore AOFAS para tornozelo e retropé melhoraram significativamente na comparação dos resultados pré e pós-operatórios. Conclusão: A osteotomia de deslocamento plantar e medial do calcâneo associada à osteotomia em cunha de adição do cuboide é capaz de melhorar os parâmetros radiológicos e clínicos de crianças com pé plano flexível. Nível de Evidência III, Estudo Comparativo Restrospectivo.

Evaluation of patients treated by telemedicine in the beginning of the COVID-19 pandemic in São Paulo, Brazil: A non-randomized clinical trial preliminary study.

We performed a pilot open-label, non-randomized controlled clinical trial in a clinic in São Paulo, Brazil in the beginning of the COVID-19 pandemic. "This medical pilot project was carried out during the pandemic of a new and unknown agent. It was necessary to find a new and safe therapeutic approach for pathogens with high potential for severity and contamination. The repositioning of safe and accessible pre-existing and approved medications and the telemedicine approach improved treated covid patients' symptoms and reduced the risk of disease transmission. The emergency application of a new medical technology was the major limitation of the study. This innovative care model is a low-cost safe strategy, and we understand that applicability can be expanded to other regions in emergency situations." The 187 patients of the study (mean age of 37.6 ± 15,6 years) were divided into four groups: (1) asymptomatic, (2) mild symptoms, (3) moderate symptoms and (4) severe symptoms and were followed up for five days. A drug intervention was performed in group 3 and the patients of Group 4 were oriented to seek hospital care. Of all the patients, 23.0% were asymptomatic, 29.4% reported mild symptoms, 43.9% moderate symptoms and 3.7% severe symptoms. Three patients were hospitalized and discharged after recovery. Our results indicate that the use of telemedicine with diagnosis and drug treatment is a safe and effective strategy to reduce overload of health services and the exposure of healthcare providers and the population. The patients that initiated the treatment in the early stages of the disease presented satisfactory clinical response, reducing the need of face-to-face consultations and hospitalizations. The patients who followed the protocol treatment for COVID-19 with hydroxychloroquine and azithromycin for five days presented statistically significant improvement of clinical symptoms when compared to moderate patients who opted for not following the protocol (p < 0.05) and to all no treatment patients (p < 0.001).

Predictors of severe hemolytic anemia and its impact on major outcomes in systemic lupus erythematosus: Data from a multiethnic Latin American cohort.

OBJECTIVE: To determine the predictors of the occurrence of severe autoimmune hemolytic anemia (AIHA) and its impact on damage accrual and mortality in SLE patients. METHODS: Factors associated with time to severe AIHA (hemoglobin level ≤7 g/dL) occurring from the onset of SLE symptoms were examined by Cox proportional hazards regressions. The association of severe AIHA with mortality was examined by logistic regression analyses while its impact on damage was by negative binomial regression. RESULTS: Of 1,349 patients, 49 (3.6%) developed severe AIHA over a mean (SD) follow-up time of 5.4 (3.8) years. The median time from the first clinical manifestation to severe AIHA was 111 days (IQR 43-450). By multivariable analysis, male sex (HR 2.26, 95% CI 1.02-4.75, p = 0.044), and higher disease activity at diagnosis (HR 1.04, 95% CI 1.01-1.08, p = 0.025) were associated with a shorter time to severe AIHA occurrence. Of the SLEDAI descriptors, only hematologic (leukopenia and/or thrombocytopenia) showed a certain trend toward significance in the multivariable analysis (HR 2.36, 95% CI 0.91-6.13, p = 0.0772). Severe AIHA contributed neither to damage nor to mortality. CONCLUSIONS: Severe AIHA occurs during the early course of SLE. Male sex and higher disease activity at diagnosis emerged as independent predictors of a shorter time to severe AIHA occurrence. Although not statistically significant, hematological abnormalities at SLE diagnosis could predict the occurrence of severe AIHA in a shorter time. Damage and mortality did not seem to be impacted by the occurrence of severe AIHA.

Modified mubarak technique for flexible flatfoot correction in children and adolescents / Técnica de mubarak modificado para correção do pé plano flexível de crianças e adolescentes

ABSTRACT Objective: To describe the technique, analyze possible radiographic correction and evaluate the clinical result of medial and plantar calcaneal displacement osteotomy associated with opening wedge cuboid osteotomy for flexible flatfoot correction. Methods: 23 patients (30 feet) diagnosed with flexible flat foot treated with plantar and medial calcaneal displacement osteotomy associated with opening wedge cuboid osteotomy were evaluated retrospectively. In the lateral radiographs calcaneal pitch and Meary's angle were the radiographic parameters evaluated; while the talonavicular coverage angle was evaluated in the anteroposterior radiographs. To assess the clinical outcome of the surgical procedure, the American Orthopedic Foot and Ankle Society Score (AOFAS) for the ankle and hindfoot was adopted. Results: The mean values of the evaluated angles and AOFAS score for ankle and hindfoot significantly improved when comparing pre- and postoperative values. Conclusion: Plantar and medial calcaneal displacement osteotomy associated with an opening wedge cuboid osteotomy is able to improve radiological and clinical parameters of child patients with flexible flatfoot. Level of Evidence III, Retrospective Comparative Study.

RESUMO Objetivo: Descrever a técnica, analisar possíveis correções radiográficas e avaliar o resultado clínico da osteotomia de deslocamento medial e plantar do calcâneo associada à osteotomia em cunha de adição do cuboide para correção do pé plano flexível de crianças. Métodos: Foram avaliados retrospectivamente 23 pacientes (30 pés) com diagnóstico de pé plano flexível tratadas com osteotomia de deslocamento plantar e medial do calcâneo associada à osteotomia em cunha de adição do cuboide. Os parâmetros radiográficos avaliados nas imagens em perfil foram o pitch do calcâneo e o ângulo de Meary, enquanto nas radiografias anteroposteriores o ângulo de cobertura do tálus. Para avaliar o resultado clínico do procedimento cirúrgico, foi adotado o escore da American Orthopaedic Foot and Ankle Society (AOFAS) para tornozelo e retropé. Resultados: Os valores médios dos ângulos avaliados e do escore AOFAS para tornozelo e retropé melhoraram significativamente na comparação dos resultados pré e pós-operatórios. Conclusão: A osteotomia de deslocamento plantar e medial do calcâneo associada à osteotomia em cunha de adição do cuboide é capaz de melhorar os parâmetros radiológicos e clínicos de crianças com pé plano flexível. Nível de Evidência III, Estudo Comparativo Restrospectivo.

COVID-19 was not associated or trigger disease activity in spondylarthritis patients: ReumaCoV-Brasil cross-sectional data.

OBJECTIVES: To evaluate the disease activity before and after COVID-19 and risk factors associated with outcomes, including hospitalization, intensive care unit (ICU) admission, mechanical ventilation (MV) and death in patients with spondylarthritis (SpA). METHODS: ReumaCoV Brazil is a multicenter prospective cohort of immune-mediated rheumatic diseases (IMRD) patients with COVID-19 (case group), compared to a control group of IMRD patients without COVID-19. SpA patients enrolled were grouped as axial SpA (axSpA), psoriatic arthritis (PsA) and enteropathic arthritis, according to usual classification criteria. RESULTS: 353 SpA patients were included, of whom 229 (64.9%) were axSpA, 118 (33.4%) PsA and 6 enteropathic arthritis (1.7%). No significant difference was observed in disease activity before the study inclusion comparing cases and controls, as well no worsening of disease activity after COVID-19. The risk factors associated with hospitalization were age over 60 years (OR = 3.71; 95% CI 1.62-8.47, p = 0.001); one or more comorbidities (OR = 2.28; 95% CI 1.02-5.08, p = 0.001) and leflunomide treatment (OR = 4.46; 95% CI 1.33-24.9, p = 0.008). Not having comorbidities (OR = 0.11; 95% CI 0.02-0.50, p = 0.001) played a protective role for hospitalization. In multivariate analysis, leflunomide treatment (OR = 8.69; CI = 95% 1.41-53.64; p = 0.023) was associated with hospitalization; teleconsultation (OR = 0.14; CI = 95% 0.03-0.71; p = 0.01) and no comorbidities (OR = 0.14; CI = 95% 0.02-0.76; p = 0.02) remained at final model as protective factor. CONCLUSIONS: Our results showed no association between pre-COVID disease activity or that SARS-CoV-2 infection could trigger disease activity in patients with SpA. Teleconsultation and no comorbidities were associated with a lower hospitalization risk. Leflunomide remained significantly associated with higher risk of hospitalization after multiple adjustments.

Does sensitization by SARS-CoV-2 immune complexes trigger DRESS syndrome?

The diagnosis of coronavirus disease (COVID-19) has been a great challenge since the infection affects not only the respiratory system, but also different organs, given the intense inflammatory and autoimmune reaction triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Herein we present a case of a 36-year-old male patient, with some comorbidities and previous use of carbamazepine, who developed a severe condition triggered by COVID-19, including extensive exfoliative erythroderma and severe impairment of liver function, which lasted approximately 80 days.

Does sensitization by SARS-CoV-2 immune complexes trigger DRESS syndrome?

Abstract The diagnosis of coronavirus disease (COVID-19) has been a great challenge since the infection affects not only the respiratory system, but also different organs, given the intense inflammatory and autoimmune reaction triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Herein we present a case of a 36-year-old male patient, with some comorbidities and previous use of carbamazepine, who developed a severe condition triggered by COVID-19, including extensive exfoliative erythroderma and severe impairment of liver function, which lasted approximately 80 days.

Intestinal microbiota and active systemic lupus erythematosus: a systematic review.

BACKGROUND: Systemic Lupus Erythematosus (SLE) is an autoimmune disease, characterized by being multi-systemic and, therefore, reaching various organs and affecting mainly young women. Its pathogenesis comprehends many factors, including the interaction between microbiota and immune system. This systematic review assessed the relationship between intestinal microbiota and SLE in activity, highlighting microbiota representative patterns regarding quantity and diversity. METHODS: This study considered researches carried out in patients with SLE, with no restriction of age or gender, which fulfilled the classification criteria of either Systemic Lupus International Collaborating Clinic (SLICC), American College of Rheumatology (ACR) or European League Against Rheumatism (EULAR) and used the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) to classify disease in activity or remission were included. The search was carried out from October, 2020 to January, 2021 using the following databases: Medline via Pubmed, Scopus, and Embase. Five papers were included with a total of 288 participants with SLE. RESULTS: Regarding microbiota in patients with SLE in activity, there was significant increase in the following genera: Lactobacillus, Streptococcus, Megasphaera, Fusobacterium, Veillonella, Oribacterium, Odoribacter, Blautia, and Campylobacter. On the other hand, decrease in Faecalibacterium and Roseburia genera as well as Ruminococcus gnavus species was observed in remission cases, showing differences between the microbiota profile in SLE in activity and in remission. CONCLUSIONS: Results suggest that dysbiosis may be involved in the disease activity process. TRIAL REGISTRATION: CRD42021229322 .

Factors associated with neuropsychiatric involvement in Latin American patients with systemic lupus erythematosus.

INTRODUCTION: Factors related to presentation of neuropsychiatric (NP) SLE manifestations, early in the course of the disease, and during follow up have not been clearly established. PURPOSE: To identify disease and non-disease related factors associated with NP manifestations in early SLE. METHODS: We included 1193 patients from the GLADEL inception cohort free of NP involvement at cohort entry. We evaluated the association of demographic, clinical and laboratory data with NP involvement during follow-up. STATISTICAL METHODS: Independent factors associated with NP involvement were identified using a multivariable Cox regression model. RESULTS: Factors independently associated with NP manifestations were: mestizo ethnicity (HR 1.701, 95% CI 1.282-2.258, p = 0.0002), myalgias/myositis (HR 1.832, 95% CI 1.335-2.515, p = 0.0002), pneumonitis (HR 2.476, 95% CI 1.085-5.648, p = 0.0312), shrinking lung (HR 2.428, 95% CI 1.074-5.493, p = 0.0331) and hemolytic anemia (HR 1.629, 95% CI 1.130-2.347, p = 0.0089). Longer disease duration at cohort entry (13 to 24 months) was associated with a lower risk of developing NP manifestations (HR 0.642, 95% CI 0.441-0.934, p = 0.0206). CONCLUSIONS: Patients with myalgias/myositis, pneumonitis, shrinking lung and hemolytic anemia are at higher risk of NP involvement, whereas longer disease duration at cohort entry is associated with a lower risk of developing NP involvement.

Intestinal microbiota and active systemic lupus erythematosus: a systematic review

Abstract Background: Systemic Lupus Erythematosus (SLE) is an autoimmune disease, characterized by being multi-systemic and, therefore, reaching various organs and affecting mainly young women. Its pathogenesis comprehends many factors, including the interaction between microbiota and immune system. This systematic review assessed the relationship between intestinal microbiota and SLE in activity, highlighting microbiota representative patterns regarding quantity and diversity. Methods: This study considered researches carried out in patients with SLE, with no restriction of age or gender, which fulfilled the classification criteria of either Systemic Lupus International Collaborating Clinic (SLICC), American College of Rheumatology (ACR) or European League Against Rheumatism (EULAR) and used the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) to classify disease in activity or remission were included. The search was carried out from October, 2020 to January, 2021 using the following databases: Medline via Pubmed, Scopus, and Embase. Five papers were included with a total of 288 participants with SLE. Results: Regarding microbiota in patients with SLE in activity, there was significant increase in the following genera: Lactobacillus, Streptococcus, Megasphaera, Fusobacterium, Veillonella, Oribacterium, Odoribacter, Blautia, and Campylobacter. On the other hand, decrease in Faecalibacterium and Roseburia genera as well as Ruminococcus gnavus species was observed in remission cases, showing differences between the microbiota profile in SLE in activity and in remission. Conclusions: Results suggest that dysbiosis may be involved in the disease activity process. Trial registration: CRD42021229322 .

Predictors of renal damage in systemic lupus erythematous patients: data from a multiethnic, multinational Latin American lupus cohort (GLADEL).

AIM: A decrease in proteinuria has been considered protective from renal damage in lupus nephritis (LN), but a cut-off point has yet to be established. The aim of this study was to identify the predictors of renal damage in patients with LN and to determine the best cut-off point for a decrease in proteinuria. METHODS: We included patients with LN defined clinically or histologically. Possible predictors of renal damage at the time of LN diagnosis were examined: proteinuria, low complement, anti-double-stranded DNA antibodies, red cell casts, creatinine level, hypertension, renal activity (assessed by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)), prednisone dose, immunosuppressive drugs and antimalarial use. Sociodemographic variables were included at baseline. Proteinuria was assessed at baseline and at 12 months, to determine if early response (proteinuria <0.8 g/day within 12 months since LN diagnosis) is protective of renal damage occurrence. Renal damage was defined as an increase of one or more points in the renal domain of The Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) Damage Index (SDI). Cox regression models using a backward selection method were performed. RESULTS: Five hundred and two patients with systemic lupus erythematosus patients were included; 120 patients (23.9%) accrued renal damage during their follow-up. Early response to treatment (HR=0.58), antimalarial use (HR=0.54) and a high SES (HR=0.25) were protective of renal damage occurrence, whereas male gender (HR=1.83), hypertension (HR=1.86) and the renal component of the SLEDAI (HR=2.02) were risk factors for its occurrence. CONCLUSIONS: Early response, antimalarial use and high SES were protective of renal damage, while male gender, hypertension and higher renal activity were risk factors for its occurrence in patients with LN.

Predictors of Remission and Low Disease Activity State in Systemic Lupus Erythematosus: Data from a Multiethnic, Multinational Latin American Cohort.

OBJECTIVE: To determine the predictors of remission and low disease activity state (LDAS) in patients with systemic lupus erythematosus (SLE). METHODS: Three disease activity states were defined: Remission = SLE Disease Activity Index (SLEDAI) = 0 and prednisone ≤ 5 mg/day and/or immunosuppressants (maintenance dose); LDAS = SLEDAI ≤ 4, prednisone ≤ 7.5 mg/day and/or immunosuppressants (maintenance dose); and non-optimally controlled state = SLEDAI > 4 and/or prednisone > 7.5 mg/day and/or immunosuppressants (induction dose). Antimalarials were allowed in all groups. Patients with at least 2 SLEDAI reported and not optimally controlled at entry were included in these analyses. Outcomes were remission and LDAS. Multivariable Cox regression models (stepwise selection procedure) were performed for remission and for LDAS. RESULTS: Of 1480 patients, 902 were non-optimally controlled at entry; among them, 196 patients achieved remission (21.7%) and 314 achieved LDAS (34.8%). Variables predictive of a higher probability of remission were the absence of mucocutaneous manifestations (HR 1.571, 95% CI 1.064-2.320), absence of renal involvement (HR 1.487, 95% CI 1.067-2.073), and absence of hematologic involvement (HR 1.354, 95% CI 1.005-1.825); the use of immunosuppressive drugs before the baseline visit (HR 1.468, 95% CI 1.025-2.105); and a lower SLEDAI score at entry (HR 1.028, 95% CI 1.006-1.051 per 1-unit decrease). These variables were predictive of LDAS: older age at entry, per 5-year increase (HR 1.050, 95% CI 1.004-1.098); absence of mucocutaneous manifestations (HR 1.401, 95% CI 1.016-1.930) and renal involvement (HR 1.344, 95% CI 1.049-1.721); and lower SLEDAI score at entry (HR 1.025, 95% CI 1.009-1.042). CONCLUSION: Absence of mucocutaneous, renal, and hematologic involvement, use of immunosuppressive drugs, and lower disease activity early in the course of the disease were predictive of remission in patients with SLE; older age was predictive of LDAS.

Efecto de los antimaláricos sobre los diferentes dominios del índice de daño SLICC en pacientes de la cohorte GLADEL / Effect of antimalarials on the different domains of the SLICC damage index in patients of the GLADEL cohort

Objetivos: Estimar el efecto de los antimaláricos (AM) sobre los diferentes dominios del índice de daño SLICC (SDI). Métodos: Se estudiaron pacientes con diagnóstico clínico reciente (≤2 años) de lupus eritematoso sistémico (LES) de la cohorte GLADEL. Variable de estudio: aumento en los dominios del SDI desde el ingreso a la cohorte. Variables independientes: características sociodemográficas, clínicas, laboratorio y tratamientos. El efecto de los AM, como variable dependiente del tiempo, sobre los dominios más frecuentes del SDI (ajustado por factores de confusión) fue examinado con un modelo de regresión de Cox multivariado. Resultados: De 1466 pacientes estudiados, 1049 (72%) recibieron AM con un tiempo medio de exposición de 30 meses (Q1-Q3: 11-57) y 665 pacientes (45%) presentaron daño durante un seguimiento medio de 24 meses (Q1-Q3: 8-55); 301 eventos fueron cutáneos, 208 renales, 149 neuropsiquiátricos, 98 musculoesqueléticos, 88 cardiovasculares y 230 otros. Después de ajustar por factores de confusión, el uso de AM se asoció a un menor riesgo de daño renal (HR 0,652; IC 95%: 0,472-0,901) y en el límite de la significancia estadística (HR 0,701, IC 95%: 0,481-1,024) para el dominio neuropsiquiátrico. Conclusión: En GLADEL, el uso de AM se asoció independientemente a un menor riesgo de daño acumulado renal.

Objective: To assess the effects of antimalarials (AM) over the items of the SLICC Damage Index (SDI). Methods: Patients with recent (≤2 years) diagnosis of systemic lupus erythematosus (SLE) from the GLADEL cohort were studied. End-point: increase in items SDI since cohort entry. Independent variables (socio-demographic, clinical, laboratory and treatment) were included. The effect of AM as a time dependent variable on most frequent SDI items (adjusting for potential confounders) was examined with a multivariable Cox regression model. Results: Of the 1466 patients included in this analysis, 1049 (72%) received AM with a median exposure time of 30 months (Q1-Q3: 11-57). Damage occurred in 665 (45%) patients during a median follow-up time of 24 months (Q1-Q3: 8-55). There were 301 integument, 208 renal, 149 neuropsychiatric, 98 musculoskeletal, 88 cardiovascular and 230 others less frequently represented damages. After adjusting for potential confounders at any time during follow-up, a lower risk of renal damage (HR 0.652; 95% CI: 0.472-0.901) and borderline for neuropsychiatric damage (HR 0.701, 95% CI: 0.481-1.024) was found. Conclusion: In the GLADEL cohort, after adjustment for possible confounding factors, AM were independently associated with a reduced risk of renal damage accrual.

A Novel Missense GLA Mutation (p.G35V) Detected in Hemodialysis Screening Leads to Severe Systemic Manifestations of Fabry Disease in Men and Women.

BACKGROUND/AIMS: Fabry disease (FD), an X-linked lysosomal storage disorder, leads to accumulation of globotriaosylceramide. Screening in dialysis patients may identify genetic variants of unknown clinical significance. We aimed to characterize the pathogenicity of a novel GLA gene mutation identified during hemodialysis screening and the histologic findings of early Fabry nephropathy. METHODS: One out of 108 male hemodialysis patients screened for FD presented low α-galactosidase A activity. A novel missense mutation (p.G35V) in the GLA gene was detected. Family screening identified 11 additional cases (8 women). Clinical investigation was conducted in 10 patients (index case and 9 relatives). Pathogenicity of the new mutation was investigated by clinical and laboratory tests, cardiac and cranial magnetic resonance imaging, and kidney biopsy. RESULTS: Cardiac manifestations were detected in most patient from both genders, such as left ventricular hypertrophy and short PR interval. White matter lesion was present in 3 women. Pulvinar lesion of the thalamus and ischemic stroke were detected in male patients. Abnormal glomerular filtration rate (GFR) and/or albuminuria were present in 5 patients (3 women). Renal biopsies (n = 7) revealed globotriaosylceramide deposits in different cell types and foot processes effacement in all patients, including women with normal albuminuria. Despite a normal GFR, tubulointerstitial fibrosis ranging from 5 to 20% was present in young women and men with normal or high albuminuria, respectively. CONCLUSION: The novel missense mutation p.G35V leads to severe systemic manifestations of FD in men and women. Kidney histological changes, including tubulointerstitial fibrosis, may predate albuminuria and GFR changes in adult women. Novel non-invasive markers are required for early detection of Fabry nephropathy.

Rheumatic fever: update on the Jones criteria according to the American Heart Association review - 2015 / Febre reumática: atualização dos critérios de Jones à luz da revisão da American Heart Association - 2015

ABSTRACT Rheumatic fever is still currently a prevalent disease, especially in developing countries. Triggered by a Group A β-hemolytic Streptococcus infection, the disease may affect genetically predisposed patients. Rheumatic carditis is the most important of its clinical manifestations, which can generate incapacitating sequelae of great impact for the individual and for society. Currently, its diagnosis is made based on the Jones criteria, established in 1992 by the American Heart Association. In 2015, the AHA carried out a significant review of these criteria, with new diagnostic parameters and recommendations. In the present study, the authors perform a critical analysis of this new review, emphasizing the most relevant points for clinical practice.

RESUMO A febre reumática ainda é uma doença prevalente nos tempos atuais, sobretudo nos países em desenvolvimento. Deflagrada por uma infecção pelo Streptococcus β-hemolítico do grupo A, pode afetar pacientes geneticamente predispostos. A cardite reumática é a mais importante das manifestações clínicas, pode gerar sequelas incapacitantes e de grande impacto para o indivíduo e para a sociedade. Atualmente, seu diagnóstico é feito baseado nos Critérios de Jones, estabelecidos em 1992 pela American Heart Association (AHA). Em 2015, a AHA procedeu a uma significativa revisão desses critérios, com novos parâmetros e recomendações diagnósticas. No presente estudo, os autores fazem uma análise crítica dessa nova revisão e enfatizam os pontos de maior relevância para a prática clínica.

Rheumatic fever: update on the Jones criteria according to the American Heart Association review - 2015.

Rheumatic fever is still currently a prevalent disease, especially in developing countries. Triggered by a Group A ß-hemolytic Streptococcus infection, the disease may affect genetically predisposed patients. Rheumatic carditis is the most important of its clinical manifestations, which can generate incapacitating sequelae of great impact for the individual and for society. Currently, its diagnosis is made based on the Jones criteria, established in 1992 by the American Heart Association. In 2015, the AHA carried out a significant review of these criteria, with new diagnostic parameters and recommendations. In the present study, the authors perform a critical analysis of this new review, emphasizing the most relevant points for clinical practice.

Medication adherence in patients in treatment for rheumatoid arthritis and systemic lupus erythematosus in a university hospital in Brazil.

Medication adherence is essential for the control of symptoms and progression of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). The aim of the study was to investigate medication adherence in outpatients in treatment for RA and SLE in a university hospital in Brazil. This was a quantitative, cross-sectional analytical study. A total of 92 patients (55 RA patients and 37 SLE patients) were included in the study. A structured questionnaire for patients' interview and a form for collecting data from medical records were used for data collection. Adherence to drug treatment was assessed by the Morisky scale questionnaire. Data storage and analysis were performed using Epi Info 3.5.4 and statistical analysis by Stata/SE 12.0. The Pearson's chi-squared test and Fisher's exact test were applied for statistical and bivariate analyses. For multivariate data analysis the Poisson regression and the Wald test were used. The prevalence of adherence to drug treatment was 16.4% in RA patients and 45.9% in SLE patients. The final model of the multivariate analysis demonstrated associations between medication adherence and the following covariates for both RA and SLE groups: duration of therapy for rheumatic disease at the institution greater than 15 years and presence of more than six chronic comorbidities. The parameter "acquisition of medication at the high-cost pharmacy" was differently associated with medication adherence by group, and for the SLE group, living outside the city of Goiânia was a protective factor associated with adherence. This study demonstrated a low prevalence of medication adherence in patients in treatment for RA and SLE treated at this institution. These findings will serve as a base for future studies to elucidate what factors may positively or negatively affect medication adherence in this population. In addition, multidisciplinary approaches are needed to enhance adherence to drug treatment in patients in treatment for rheumatic disease.

The impact of comorbidities on the physical function in patients with rheumatoid arthritis.

OBJECTIVES: To investigate the association of comorbidities with mobility limitation and functional disability in patients with rheumatoid arthritis and to identify which comorbidity indicator is the most appropriate to determine this association. METHODS: Sixty rheumatoid arthritis patients were enrolled in a cross-sectional study for a period of 11 months. Comorbidities were assessed using three indicators: (i) the total number of comorbidities; (ii) the Charlson comorbidity index; and (iii) the functional comorbidity index. Disease activity was assessed using the Disease Activity Score 28. Functional capacity was measured using the Health Assessment Questionnaire, and mobility was measured using Timed Up and Go Test and Five-Times-Sit-to-Stand Test. Statistical analysis was performed using a stepwise log-linear multiple regression with a significance level of 5%. RESULTS: In the final model, only comorbidity was associated with mobility limitation. The functional comorbidity index score explained 19.1% of the variability of the Five-Times-Sit-to-Stand Test (coefficient of determination [R(2)]=0.191) and 19.5% of the Timed Up and Go Test variability (R(2)=0.195). With regard to functional disability, the associated factors were comorbidity and disease activity, which together explained 32.9% of the variability of the Health Assessment Questionnaire score (adjusted R(2)=0.329). CONCLUSION: Comorbidities were associated with mobility limitation and functional disability in rheumatoid arthritis patients. The functional comorbidity index proved to be an appropriate comorbidity indicator to determine this association.