Factors Associated With Mortality in Patients With Immune-Mediated Rheumatic Diseases and COVID-19 From Latin America: Data From Argentina, Mexico, and Brazil.

OBJECTIVE: To describe characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with rheumatic immune-mediated inflammatory diseases (IMIDs) from Argentina, Mexico and Brazil, and to assess factors associated with mortality in this population. METHODS: Data from 3 national registries, SAR-COVID (Argentina), CMR-COVID (Mexico), and ReumaCoV-Brasil (Brazil), were combined. Adult patients with IMIDs and SARS-CoV-2 infection were recruited. Sociodemographic data, comorbidities, IMID clinical characteristics and treatment, and SARS-CoV-2 infection presentation and outcomes were recorded. RESULTS: A total of 4827 individuals were included: 2542 (52.7%) from SAR-COVID, 1167 (24.2%) from CMR-COVID, and 1118 (23.1%) from ReumaCoV-Brasil. Overall, 82.1% were female with a mean age of 49.7 (SD, 14.3) years; 22.7% of the patients were hospitalized, and 5.3% died because of COVID-19 (coronavirus disease 2019). Argentina and Brazil had both 4% of mortality and Mexico 9.4%. In the multivariable analysis, older age (≥60 years; odds ratio [OR], 7.4; 95% confidence interval [CI], 4.6-12.4), male sex (OR, 1.5; 95% CI, 1.1-2.1), living in Mexico (OR, 3.0; 95% CI, 2.0-4.4), comorbidity count (1 comorbidity: OR, 1.5; 95% CI, 1.0-2.1), diagnosis of connective tissue disease or vasculitis (OR, 1.8; 95% CI, 1.3-2.4), and other diseases (OR, 2.6; 95% CI, 1.6-4.1) compared with inflammatory joint disease, high disease activity (OR, 4.2; 95% CI, 2.5-7.0), and treatment with glucocorticoids (OR, 1.9; 95% CI, 1.4-2.5) or rituximab (OR, 4.2; 95% CI, 2.7-6.6) were associated with mortality. CONCLUSIONS: Mortality in patients with IMIDs was particularly high in Mexicans. Ethnic, environmental, societal factors, and different COVID-19 mitigation measures adopted have probably influenced these results.

Obstetric outcomes in women with rheumatic disease and COVID-19 in the context of vaccination status.

OBJECTIVE: To describe obstetric outcomes based on COVID-19 vaccination status, in women with rheumatic and musculoskeletal diseases (RMDs) who developed COVID-19 during pregnancy. METHODS: Data regarding pregnant women entered into the COVID-19 Global Rheumatology Alliance registry from 24 March 2020-25 February 2022 were analysed. Obstetric outcomes were stratified by number of COVID-19 vaccine doses received prior to COVID-19 infection in pregnancy. Descriptive differences between groups were tested using the chi-squared or Fisher's exact test. RESULTS: There were 73 pregnancies in 73 women with RMD and COVID-19. Overall, 24.7% (18) of pregnancies were ongoing, while of the 55 completed pregnancies, 90.9% (50) of pregnancies resulted in livebirths. At the time of COVID-19 diagnosis, 60.3% (n = 44) of women were unvaccinated, 4.1% (n = 3) had received one vaccine dose while 35.6% (n = 26) had two or more doses. Although 83.6% (n = 61) of women required no treatment for COVID-19, 20.5% (n = 15) required hospital admission. COVID-19 resulted in delivery in 6.8% (n = 3) of unvaccinated women and 3.8% (n = 1) of fully vaccinated women. There was a greater number of preterm births (PTB) in unvaccinated women compared with fully vaccinated 29.5% (n = 13) vs 18.2% (n = 2). CONCLUSIONS: In this descriptive study, unvaccinated pregnant women with RMD and COVID-19 had a greater number of PTB compared with those fully vaccinated against COVID-19. Additionally, the need for COVID-19 pharmacological treatment was uncommon in pregnant women with RMD regardless of vaccination status. These results support active promotion of COVID-19 vaccination in women with RMD who are pregnant or planning a pregnancy.

Active lupus in Argentina: Results of a multicenter and national registry.

OBJECTIVE: To evaluate the association between patients' characteristics and disease activity in an Argentine lupus registry. METHODS: Cross-sectional study. Disease activity was stratified into: Remission off-treatment: SLEDAI = 0, without prednisone and immunosuppressive drugs. Low disease activity Toronto Cohort (LDA-TC): SLEDAI ≤2, without prednisone or immunosuppressive drugs. Modified lupus low disease activity (mLLDAS): SLEDAI score of ≤4, with no activity in major organ systems and no new features, prednisone of ≤10 mg/day and/or immunosuppressive drugs (maintenance dose) and Active disease: SLEDAI score of >4 and prednisone >10 mg/day and immunosuppressive drugs. A descriptive analysis and logistic regression model were performed. RESULTS: A total of 1346 patients were included. Of them, 1.6% achieved remission off steroids, 0.8% LDA-TC, 12.1% mLLDAS and the remaining 85.4% had active disease. Active disease was associated with younger age (p ≤ 0.001), a shorter time to diagnosis (p ≤ 0.001), higher frequency of hospitalizations (p ≤ 0.001), seizures (p = 0.022), serosal disease (p ≤ 0.001), nephritis (p ≤ 0.001), higher SDI (p ≤ 0.001), greater use of immunosuppressive therapies and higher doses of prednisone compared to those on mLLDAS. In the multivariable analysis, the variables associated with active disease were the presence of pleuritis (OR 2.1, 95% CI 1.2-3.9; p = 0.007), persistent proteinuria (OR 2.5, 95% CI 1.2-5.5; p ≤ 0.011), nephritis (OR 2.5, 95% CI 1.2-5.6; p = .018) and hospitalizations (OR 8.9, 95% CI 5.3-16.0; p ≤ 0.001) whereas age at entry into the registry was negatively associated with it (OR 0.9, 95% CI 0.9-1.0; p = 0.029). CONCLUSION: Active disease was associated with shorter time to diagnosis, worse outcomes (SDI and hospitalizations) and renal, neurological and serosal disease.

Does the Use of Immunosuppressive Drugs Impact on SARS-CoV-2 Infection Outcome? Data From A National Cohort of Patients With Immune-Mediated Inflammatory Diseases (SAR-COVID Registry).

BACKGROUND/OBJECTIVE: This study describes the impact of immunomodulatory and/or immunosuppressive (IM/IS) drugs in the outcomes of COVID-19 infection in a cohort of patients with immune-mediated inflammatory diseases (IMIDs). METHODS: Adult patients with IMIDs with a confirmed SARS-CoV-2 infection were included. Data were reported by the treating physician between August 13, 2020 and July 31, 2021. Sociodemographic data, comorbidities, and DMARDs, as well as clinical characteristics, complications, and treatment of the SARS-CoV-2 infection, were recorded. Descriptive analysis and multivariable logistic regression models were carried out. RESULTS: A total of 1672 patients with IMIDs were included, of whom 1402 were treated with IM/IS drugs. The most frequent diseases were rheumatoid arthritis (47.7%) and systemic lupus erythematosus (18.4%). COVID-19 symptoms were present in 95.2% of the patients. A total of 461 (27.6%) patients were hospitalized, 8.2% were admitted to the intensive care unit, and 4.4% died due to COVID-19.Patients without IM/IS treatment used glucocorticoids less frequently but at higher doses, had higher levels of disease activity, were significantly older, were more frequently hospitalized, admitted to the intensive care unit, and died due to COVID-19. After adjusting for these factors, treatment with IM/IS drugs was not associated with a worse COVID-19 outcome (World Health Organization-Ordinal Scale ≥5) (odds ratio, 1.24; 95% confidence interval, 0.73-2.06). CONCLUSIONS: SAR-COVID is the first multicenter Argentine registry collecting data from patients with rheumatic diseases and SARS-CoV-2 infection. After adjusting for relevant covariates, treatment with IM/IS drugs was not associated with severe COVID-19 in patients with IMIDs. STUDY REGISTRATION: This study has been registered in ClinicalTrials.gov under the number NCT04568421.

Multicenter lupus register from Argentina, the RELESSAR database: Influence of ethnicity on disease phenotype.

OBJECTIVE: The objective is to describe the main characteristics of patients with systemic lupus erythematosus (SLE) in Argentina and to examine the influence of ethnicity on the expression of the disease. PATIENTS AND METHODS: RELESSAR is a multicentre register carried out by 106 researchers from 67 rheumatologic Argentine centres. It is a cross-sectional study of SLE (1982/1997 ACR) patients. RELESSAR electronic database includes demographic, cumulative SLE manifestations, SELENA-SLEDAI, SLICC-SDI, Katz's severity and Charlson's comorbidity indexes and treatment patterns. RESULTS: We included 1,610 patients, 91.7% were female with a median age at diagnosis of 28.1 ± 12.8; 96.2% met ≥4 ACR 1982/97 criteria. Frequent manifestations were arthritis (83.5%), malar rash (79.5%), photosensitivity (75.3%), haematological (63.8%) and renal disease (47.4%), antinuclear antibodies (96%), anti-dsDNA (66.5%) and anti-Smith antibodies (29%). The mean Selena-SLEDAI score at last visit was 3.18 (SD 4.3) and mean SDI was 1 (SD 1.3). The accumulated treatments most frequently used were antimalarials (90.4%), corticosteroids (90%), azathioprine (31.8%), intravenous cyclophosphamide (30.2%), mycophenolate mofetil or mycophenolic acid (24.5%), methotrexate (19.3%), belimumab 5.3% and rituximab 5.1%. Refractory lupus was diagnosed in 9.3% of the cases. The main causes of death were lupus activity (25.0%), activity and concomitant infections (25.0%), infections (18.2%), vascular disease (13.6%) and cancer (4.5%). Mortality was associated with higher SLEDAI, Katz, damage indexes and comorbidities. Of the 1610 patients included, 44.6% were Caucasian, 44.5% Mestizo, 8.1% Amerindian and 1.2% Afro-Latin American. Mestizo patients had higher male representation, low socioeconomic status, more inadequate medical coverage, fewer formal years of education and shorter disease duration. Polyadenopathies and Raynaud's phenomenon were more frequent in Caucasians. In the logistic regression analysis higher damage index (OR 1.28, CI 95% 1.02-1.61, p = 0.03) remained associated to mestizo ethnicity. CONCLUSIONS: This study represents the largest number of adult patients with SLE studied in Argentina. Caucasian patients were differentiated by having Raynaud's phenomenon and polyadenopathy more frequently, while patients of Mestizo origin had higher damage indexes.

Pathogenic mechanisms contributing to thrombocytopenia in patients with systemic lupus erythematosus.

SummarySystemic lupus erythematosus (SLE) is an autoimmune condition developing thrombocytopenia in about 10-15% of cases, however, mechanisms leading to low platelet count were not deeply investigated in this illness. Here we studied possible causes of thrombocytopenia, including different mechanisms of platelet clearance and impairment in platelet production. Twenty-five SLE patients with and without thrombocytopenia were included. Platelet apoptosis, assessed by measurement of loss of mitochondrial membrane potential, active caspase 3 and phosphatidylserine exposure, was found to increase in thrombocytopenic patients. Plasma from 67% SLE patients (thrombocytopenic and non-thrombocytopenic) induced loss of sialic acid (Ricinus communis agglutinin I and/or Peanut agglutinin binding) from normal platelet glycoproteins. Concerning platelet production, SLE plasma increased megakaryopoiesis (evaluated using normal human cord blood CD34+ hematopoietic progenitors), but inhibited thrombopoiesis (proplatelet count). Anti-platelet autoantibody depletion from SLE plasma reverted this inhibition. Overall, abnormalities were more frequently observed in thrombocytopenic than non-thrombocytopenic SLE patients and in those with active disease (SLEDAI≥5). In conclusion, platelet clearance due to apoptosis and desialylation, and impaired platelet production mainly due to inhibition of thrombopoiesis, could be relevant mechanisms leading to thrombocytopenia in SLE. These findings could provide a rational basis for the choice of proper therapies to correct platelet counts in these patients.[Figure: see text].

Characterization of Patients With Dermatomyositis According to Anti-Melanoma Differentiation-Associated Gene-5 Autoantibodies in Centers from 3 Latin American Countries: A Cohort Study.

BACKGROUND/OBJECTIVE: The anti-melanoma differentiation-associated protein 5 (MDA5) autoantibodies have been associated with a high frequency of interstitial lung disease (ILD) and rapidly progressive ILD (RP-ILD) in dermatomyositis (DM) patients, mainly in Asian subjects. However, there is scarce information about these parameters in Latin American patients. METHOD: This was a medical records review cohort study that included classic DM (CDM) and clinically amyopathic DM (CADM) patients from 3 Latin American countries (Argentina, Brazil, and Mexico). RESULTS: A total of 270 DM patients were evaluated: 25.9% with CADM and 74.1% with CDM. The overall prevalence of ILD and RP-ILD, respectively, was 70 (25.9%) and 4 (1.5%) of the 270 patients, and the distributions were comparable between patients with CDM and CADM. The anti-MDA5 was present in 31 (25.4%) of 122 CDM patients and in 17 (48.6%) of 35 CADM patients; it was not associated with presence of ILD and RP-ILD. However, anti-MDA5-positive CDM patients had significantly high frequency of "mechanic's hands," arthralgia, arthritis, and lower serum levels of creatine phosphokinase, whereas anti-MDA5-positive CADM patients had significantly high frequency of arthritis. Pulmonary infection and ILD are main causes of death in DM patients. CONCLUSIONS: In the present study, the prevalence of ILD in DM patients is comparable to that described in the literature, in contrast to the very low frequency of RP-ILD. In addition, the anti-MDA5 is not associated with ILD and RP-ILD, but anti-MDA5-positive DM patients present conditions that mimic antisynthetase syndrome. Pulmonary infection and ILD were the main causes of death in our sample.

Clinical and Serological Features in Latin American IgG4-Related Disease Patients Differ According to Sex, Ethnicity, and Clinical Phenotype.

BACKGROUND/OBJECTIVE: Data on IgG4-related disease (IgG4-RD) come almost exclusively from cohorts from Asia, Europe, and North America. We conducted this study to describe the clinical presentation, phenotype distribution, and association with sex, ethnicity, and serological markers in a large cohort of Latin American patients with IgG4-RD. METHODS: We performed a multicenter medical records review study including 184 Latin American IgG4-RD patients. We assigned patients to clinical phenotypes: group 1 (pancreato-hepato-biliary), group 2 (retroperitoneal/aortic), group 3 (head and neck-limited), group 4 (Mikulicz/systemic), and group 5 (undefined). We focused the analysis on how sex, ethnicity, and clinical phenotype may influence the clinical and serological presentation. RESULTS: The mean age was 50.8 ± 15 years. Men and women were equally affected (52.2% vs 48.8%). Fifty-four patients (29.3%) were assigned to group 1, 21 (11.4%) to group 2, 57 (30.9%) to group 3, 32 (17.4%) to group 4, and 20 (10.8%) to group 5. Male sex was associated with biliary tract (odds ratio [OR], 3.4; 95% confidence interval [CI], 1.36-8.26), kidney (OR, 3.4; 95% CI, 1.28-9.25), and retroperitoneal involvement (OR, 5.3; 95% CI, 1.45-20). Amerindian patients presented more frequently with atopy history and gallbladder involvement. Group 3 had a female predominance. CONCLUSIONS: Latin American patients with IgG4-RD were younger, and men and women were equally affected compared with White and Asian cohorts. They belonged more commonly to group 1 and group 3. Retroperitoneal and aortic involvement was infrequent. Clinical and serological features differed according to sex, ethnicity, and clinical phenotype.

Validation and adaptation of the Spanish version of the systemic lupus activity questionnaire (S-SLAQ) in an Argentinean population.

OBJECTIVES: To validate the systemic lupus activity questionnaire (SLAQ) in Spanish language. METHODS: The SLAQ questionnaire was translated and adapted in Spanish. Consecutive SLE patients from 8 centers in Argentina were included. A rheumatologist completed a Systemic Lupus Activity Measure (SLAM), Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)-2K, and a physician's assessment. Reliability was assessed by internal consistency (Cronbach's alpha), stability by test-retest reliability (intraclass correlation coefficient), and construct validity by evaluating the correlation with clinically relevant scores. Sensitivity and specificity for clinically significant disease activity (SLEDAI ≥6) of different S-SLAQ cut-off points were evaluated. RESULTS: We included 97 patients ((93% female, mean age: 40 years (SD14.7)). Internal consistency was excellent (Cronbach's alpha = 0.84, p < 0.001), and the intraclass correlation coefficient was 0.95 (p < 0.001). Mean score of S-SLAQ was 8.2 (SD 7.31). Correlation of S-SLAQ was moderate with Patient NRS (r= 0.63 p< 0.001), weak with SLAM-no lab (r = 0.42, p <0.001) and SLAM (r = 0.38, p < 0.0001), and very weak with SLEDAI-2K (r = 0.15, p =0.1394). Using the S-SLAQ cutoff of five points, the sensitivity was 72.2% and specificity was 37.9%, for clinically significant disease activity. CONCLUSIONS: The S-SLAQ showed good validity and reliability. A good correlation, similar to the original instrument, was observed with patient´s global disease activity. No correlation was found between S-SLAQ and gold standard disease activity measures like SLEDAI-2K and SLAM. The S-SLAQ cutoff point of 5 showed a good sensitivity to identify the active SLE population and therefore could be an appropriate screening instrument for disease activity in clinical and epidemiological studies.

Validation of the adjusted global antiphospholipid syndrome score in systemic lupus erythematosus patients in Argentina.

INTRODUCTION: Assessment of risk both for pregnancy morbidity and thrombosis in the presence of anti-phospholipid antibodies (aPL) is still a challenge in Systemic Lupus Erythematosus (SLE) patients. The Global Antiphospholipid Syndrome Score (GAPSS) takes into account the aPL profile (criteria and non-criteria aPL), the conventional cardiovascular risk factors and the autoimmune antibody profile. An adjusted model of the score (aGAPSS) excluding anti-phosphatidylserine/Prothrombin (aPS/PT), suggests that the score is able to stratify patients for their rate of events making it widely applicable in daily clinical practice. OBJECTIVE: To validate the aGAPSS in a multicentric cohort of SLE patients in Argentina. PATIENTS AND METHODS: consecutive SLE patients with and with andwithout thrombotic events from seven Rheumatologist centers were included. Traditional cardiovascular risk factors, aPL antibodies and medications received (aspirin, hydroxychloroquine and anticoagulation) were collected. The score aGAPSS was calculated for each patient at the last visit by adding together the points corresponding to the risk factors: 1 for hypertension, 3 for dyslipidemia, 4 for LA and B2GPI (IgM or IgG) antibodies and 5 for aCL (IgM or IgG) antibodies. The discriminative ability of the aGAPSS was calculated by measuring the area under the receiver operating characteristic curve (AUC). Multivariate logistic regression analysis was performed to examine the impact of multiple cardiovascular risk factors and laboratory parameters on the occurrence of thrombosis. RESULTS: Two hundred and ninety-six SLE patients were included. One-hundred and twenty-one patients (40.9%) presented thrombotic and/or pregnancy complications. Median aGAPSS was significantly higher in patients who experienced an event (thrombosis and/or pregnancy morbidity) compared with those without [4 (IQR 1-9) versus 1 (IQR 0-5); p < 0.001]. The best cut off point for the diagnosis of thrombosis and/or pregnancy complications was aGAPSS ≥4. Multivariate logistic regression analysis showed that aCL antibodies [OR 2.1 (95% CI 1.16-3.90); p = 0.015] were an independent risk factors for thrombotic events. CONCLUSIONS: This score is a simple tool, easy to apply to SLE patients in daily practice. The use of the aGAPSS could change the non-pharmacologic and pharmacologic treatment in higher risk patients to improve their survival.

Usefulness of Methotrexate in the Reduction of Relapses and Recurrences in Polymyalgia Rheumatica: An Observational Study.

OBJECTIVES: Methotrexate (MTX) has been studied with conflicting results in patients with polymyalgia rheumatica (PMR). Our objective was to evaluate the effectiveness of MTX to reduce relapses and recurrences in patients with PMR. METHODS: This observational longitudinal cohort study included 94 consecutive patients with PMR. Patients were assigned to 3 groups according to the prescribed treatment: group 1, treated with glucocorticoids (GCs) alone; group 2, treated with GCs initially plus MTX after a relapse or recurrence; and group 3, treated with GCs plus MTX since diagnosis.Factors associated with a first relapse were studied in the population. To evaluate MTX effect, patients from group 2 were evaluated comparing results from the first treatment period (GCs alone) to the second treatment period with GCs plus MTX. RESULTS: Ninety-four patients were included. The median follow-up time was 21.3 months (interquartile range [IQR], 11.7-56.2). Fifty-three patients (56.4%) were in group 1, 33 (35.1%) in group 2, and 8 (8.5%) in group 3. We found that female sex had a tendency to be associated with a first relapse (p = 0.07).In group 2, 35 relapses were identified during the first treatment period and only 8 relapses during the combined treatment period (p < 0.001). In this group, after the addition of MTX, the GCs dose at relapse was lower (5.1 vs 3 mg/d, p = 0.02) and the time to accomplish remission was shorter (22.9 vs 8.7 months, p = 0.01). There were no differences in the number of recurrences. CONCLUSIONS: The use of MTX in PMR patients who already had a relapse reduced the number of future relapses and decreased the time to achieve remission. Adding MTX allowed a reduction of GCs dose at relapse.

Long-term Outcome of Lupus Nephritis Class II in Argentine Patients: An Open Retrospective Analysis.

BACKGROUND: There is controversy in medical literature over the outcome of patients with lupus nephritis (LN) class II. The aim of this study was to explore the risk of histological transformation (HT) and possible factors related to negative response to treatment in patients with mesangial LN class II. METHODS: A retrospective and multicenter study was carried out that includes patients who had received a diagnosis of LN class II on their first renal biopsy. Creatinine, urine sediment, and proteinuria were recorded at the time of the first biopsy, 6 months, and 1, 2, and 5 years after the first biopsy. Response to treatment, HT, and long-term outcome were evaluated. RESULTS: Forty-one patients were included. The manifestation at first biopsy was proteinuria greater than 0.5 g/d in 28 patients (68.29%; 8 [28.57%] of 28 patients had nephrotic syndrome), hematuria in 18 patients (43.90%), and deterioration of renal function in 3 patients (7.31%). During the follow-up (median, 8 years; range, 1-35 years), a new biopsy was performed in 18 patients (43.90%), and in 17 patients (17/18 [94.44%]), there was HT. Median time at rebiopsy was 32 months (range, 11-305 months). Of the 18 patients who had a second biopsy, 10 (55.55%) were on hydroxychloroquine versus 100% (19/19) of patients who did not undergo the procedure (P = 0.001). A year after the first renal biopsy, there are data available from 34 patients; of them, 24 patients (70.58%) had achieved response, and 10 patients (29.41%) had no response (NR) (missing data in 7). A higher 24-hour urinary protein at 6 months was predictor of worse outcome at 1 year, with statistical significance difference for the nonresponder group (median proteinuria, 2.3 g/d [range, 0-4.7 g/d]) compared with responders (median proteinuria, 0.28 g/d [range, 0-1.7 g/d]) (P = 0.0133).In the long-term follow-up (5 years), HT was the main cause of unfavorable outcome and was measured in 78.57% of patients (11/14 patients). CONCLUSIONS: This series shows a high rate of HT in long-term follow-up. Proteinuria at 6 months made it possible to set aside patients who will have an unfavorable outcome in the long term and who will thus benefit from a more aggressive treatment. The results suggest that hydroxychloroquine had a nephroprotective effect.

Elevated IL-1ß levels in anti-Ro/SSA connective tissue diseases patients with prolonged corrected QTc interval.

OBJECTIVES: Patients with systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS) have increased IL-1ß levels. IL-1ß and other pro-inflammatory cytokines have a modulating activity on cardiac ion channels and have been associated with increased arrhythmic risk in rheumatoid arthritis patients. Likewise, adult patients with connective tissue diseases (CTDs) may have prolonged QTc intervals associated with the presence of anti-Ro/SSA antibodies. Our objective was to evaluate the presence of serum IL-1ß in subjects with CTDs, in relation to the presence of anti-Ro/SSA antibodies and QTc interval duration. METHODS: 12-lead electrocardiograms (ECG) were performed and blood was withdrawn, measuring electrolytes, IL-1ß anti-Ro/SSA antibodies by ELISA in 73 patients with CTDs. RESULTS: 55 patients were anti-Ro/SSA positive and 18 were anti-Ro/SSA negative. Patients with anti-Ro/SSA positive antibodies had a significantly greater median IL-1ß serum level: 7.29 (range: 0.17-17.3 pg/ml) compared to patients with anti-Ro/SSA negative antibodies whose median was: 1.67 (range 0.55-4.12 pg/ml) p<0.001. The mean QTc interval values obtained in both groups were not significantly different (417.7±23.1 vs. 414.7±21.2, p=0.63). The QTc interval was prolonged in 11 (20%) patients, who were all anti-Ro/SSA positive versus 0 (0 %) in anti-Ro/SSA negative patients p=0.05. Median IL-1ß levels were: 8.7 (range: 2.69-15.1 pg/ml) in patients with prolonged QTc interval versus median: 5.0 (range: 0.17-17.3 pg/ml) in those with normal QTc interval values (<440ms) p=0.006. CONCLUSIONS: IL-1ß is elevated in patients with CTDs that have both anti-Ro/SSA antibodies and prolonged QTc intervals.

Work instability in rheumatoid arthritis patients from Argentina: prevalence and associated factors.

To determine the prevalence of and associated factors to work instability (WI) in rheumatoid arthritis (RA) Argentinean patients. Observational cross-sectional study that assessing employment status in currently working RA patients. They answered the validated version of RA work instability scale (RA-WIS). High-risk WI was considered when RA-WIS was ≥17. Factors associated with high-risk WI were examined by univariable and multivariable analysis. Four-hundred and fifty RA patients were enrolled; of these, 205 patients were currently employed, but only 172 have completed questionnaires required [RA-WIS and health assessment questionnaire (HAQ-A)]. Their mean age was 49.3 ± 10.8 years; 81.3 % were female; and their mean disease duration was 8.1 ± 7.2 years. Fifty-two percent of patients were doing manual work. The mean RA-WIS score was 11.4 ± 6.8, and 41 % of patients had a high-risk WI. High-risk WI was associated with radiographic erosions (p < 0.001) and HAQ-A >0.87 (p < 0.001) in the univariable analysis, whereas in the multivariable logistic regression analysis the variables associated with a high-risk WI were as follows: HAQ-A >0.87 [odds ratio (OR) 12.31; 95 % CI 5.38-28.18] and the presence of radiographic erosions (OR 4.848; 95 % CI 2.22-10.5). In this model, having a higher monthly income (OR 0.301; 95 % CI 0.096-0.943) and a better functional class (OR 0.151; 95 % CI 0.036-0.632) were protective. Forty-one percent of RA working patients had high-risk WI. The predictors of high RA-WIS were HAQ-A ≥0.87 and radiographic erosions, whereas having a better functional class and have higher incomes were protective.

Granulomatosis with polyangiitis: recurrence presenting as ependimoplexitis.

A 55-year-old man with granulomatosis with polyangiitis (GPA) developed continuous parietal headache, malaise, nasal crusting and dry cough. Neurological exam revealed only left hand hypoesthesia in 4th and 5th finger. Brain MRI showed enlarged right choroid plexus, hyperintense periventricular white matter, thalami and right side of corpus callosum. The suspected diagnosis was ependimoplexitis due to GPA, the patient received three 500 mg methylprednisolone pulses followed by 1 mg/kg of meprednisone with gradual tapering and was switched to oral cyclophosphamide. He had complete resolution of headache. An MRI following this treatment for relapse revealed only minimal ependimal changes.

Effectiveness of methotrexate and leflunomide as corticoid-sparing drugs in patients with polymyalgia rheumatica.

Objectives: The need for glucocorticoid-sparing drugs (GCSD) remains an important issue and is an unmet need in the treatment of polymyalgia rheumatica (PMR). We therefore aimed to assess the effectiveness and safety of methotrexate (MTX) and of leflunomide (LEF) in daily clinical practice in PMR patients from Argentina. Methods: A multicentre and observational study (medical records review) of PMR patients seen between 2007 and 2023, who had at least three months of follow-up after starting a GCSD, either MTX or LEF, was performed. Results are expressed as medians and interquartile ranges [25th-75th (IQR)] for continuous variables and percentages for categorical ones. The two treatment groups were compared using χ2 test for categorical variables, Mann-Whitney U test for continuous variables and the log-rank test for time-to-event data. Crude and adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using logistic regression. In all cases, a p-value <0.05 was considered statistically significant. Results: One-hundred and eighty-six patients (79% female) with a median age of 72 years (IQR, 65-77 years) were included. One-hundred and forty-three patients (77%) were prescribed MTX (15, IQR 10-15) and 43 (23%) LEF (20 mg, fixed dose). Flare-ups (relapses and recurrences) occurred in 13 patients (7%) and were comparable between both groups. Persistent GCSD intake was observed in 145 patients (78%). Glucocorticoid (GC) withdrawal was achieved in 67 of these 145 patients (46%) and this occurred more frequently in the LEF group (P = 0.001). Furthermore, time until prednisone discontinuation was shorter in the LEF-treated patients (4.7 months, IQR 3-20 on LEF versus 31.8 months, IQR 10-82 on MTX, P = 0.000). Remission was found more frequently in the LEF group (P = 0.003). In the multivariate analysis, the probability of remission was higher with LEF therapy (P = 0.010) and this finding persisted in the subgroup analysis who were followed up < 40 months (OR 3.12, 95% CI = 1.30-7.47, P = 0.011). Conclusions: This study demonstrated the clinical effectiveness of LEF and even its superiority in achieving remission when compared with MTX as GCSD in PMR patients. Further research is needed to support these findings.

Maternal use of hydroxychloroquine is associated with a reduced risk of recurrent anti-SSA/Ro-antibody-associated cardiac manifestations of neonatal lupus.

BACKGROUND: A recent case-control study suggested a benefit of hydroxychloroquine (HCQ) in lowering the risk of cardiac manifestations of neonatal lupus (cardiac-NL) in pregnancies of anti-SSA/Ro-positive patients with systemic lupus erythematosus. A historical cohort assembled from 3 international databases was used to evaluate whether HCQ reduces the nearly 10-fold increase in risk of recurrence of cardiac-NL independently of maternal health status. METHODS AND RESULTS: Two hundred fifty-seven pregnancies of anti-SSA/Ro-positive mothers (40 exposed and 217 unexposed to HCQ) subsequent to the birth of a child with cardiac-NL were identified from 3 databases (United States, England, and France). Exposure was defined as the sustained use of HCQ throughout pregnancy with initiation before 10 weeks of gestation. The recurrence rate of cardiac-NL in fetuses exposed to HCQ was 7.5% (3 of 40) compared with 21.2% (46 of 217) in the unexposed group (P=0.050). Although there were no deaths in the exposed group, the overall case fatality rate of the cardiac-NL fetuses in the unexposed group was 21.7%. In a multivariable analysis that adjusted for database source, maternal race/ethnicity, and anti-SSB/La status, HCQ use remained significantly associated with a decreased risk of cardiac-NL (odds ratio, 0.23; 95% confidence interval, 0.06-0.92; P=0.037). Similar results were obtained with propensity score analysis, an alternative approach to adjust for possible confounding by indication. CONCLUSION: Aggregate data from a multinational effort show that in mothers at high risk of having a child with cardiac-NL, the use of HCQ may protect against recurrence of disease in a subsequent pregnancy.

Sociodemographic and clinical factors associated with poor COVID-19 outcomes in patients with rheumatic diseases: data from the SAR-COVID Registry.

BACKGROUND/OBJECTIVE: This study aims to describe the course and to identify poor prognostic factors of SARS-CoV-2 infection in patients with rheumatic diseases. METHODS: Patients ≥ 18 years of age, with a rheumatic disease, who had confirmed SARS-CoV-2 infection were consecutively included by major rheumatology centers from Argentina, in the national, observational SAR-COVID registry between August 13, 2020 and July 31, 2021. Hospitalization, oxygen requirement, and death were considered poor COVID-19 outcomes. RESULTS: A total of 1915 patients were included. The most frequent rheumatic diseases were rheumatoid arthritis (42%) and systemic lupus erythematosus (16%). Comorbidities were reported in half of them (48%). Symptoms were reported by 95% of the patients, 28% were hospitalized, 8% were admitted to the intensive care unit (ICU), and 4% died due to COVID-19. During hospitalization, 9% required non-invasive mechanical ventilation (NIMV) or high flow oxygen devices and 17% invasive mechanical ventilation (IMV). In multivariate analysis models, using poor COVID-19 outcomes as dependent variables, older age, male gender, higher disease activity, treatment with glucocorticoids or rituximab, and the presence of at least one comorbidity and a greater number of them were associated with worse prognosis. In addition, patients with public health insurance and Mestizos were more likely to require hospitalization. CONCLUSIONS: In addition to the known poor prognostic factors, in this cohort of patients with rheumatic diseases, high disease activity, and treatment with glucocorticoids and rituximab were associated with worse COVID-19 outcomes. Furthermore, patients with public health insurance and Mestizos were 44% and 39% more likely to be hospitalized, respectively. STUDY REGISTRATION: This study has been registered in ClinicalTrials.gov under the number NCT04568421. Key Points • High disease activity, and treatment with glucocorticoids and rituximab were associated with poor COVID-19 outcome in patients with rheumatic diseases. • Some socioeconomic factors related to social inequality, including non-Caucasian ethnicity and public health insurance, were associated with hospitalization due to COVID-19.

Auricular Transcutaneous Vagus Nerve Stimulation Acutely Modulates Brain Connectivity in Mice.

Brain electrical stimulation techniques take advantage of the intrinsic plasticity of the nervous system, opening a wide range of therapeutic applications. Vagus nerve stimulation (VNS) is an approved adjuvant for drug-resistant epilepsy and depression. Its non-invasive form, auricular transcutaneous VNS (atVNS), is under investigation for applications, including cognitive improvement. We aimed to study the effects of atVNS on brain connectivity, under conditions that improved memory persistence in CD-1 male mice. Acute atVNS in the cymba conchae of the left ear was performed using a standard stimulation protocol under light isoflurane anesthesia, immediately or 3 h after the training/familiarization phase of the novel object-recognition memory test (NORT). Another cohort of mice was used for bilateral c-Fos analysis after atVNS administration. Spearman correlation of c-Fos density between each pair of the thirty brain regions analyzed allowed obtaining the network of significant functional connections in stimulated and non-stimulated control brains. NORT performance was enhanced when atVNS was delivered just after, but not 3 h after, the familiarization phase of the task. No alterations in c-Fos density were associated with electrostimulation, but a significant effect of atVNS was observed on c-Fos-based functional connectivity. atVNS induced a clear reorganization of the network, increasing the inter-hemisphere connections and the connectivity of locus coeruleus. Our results provide new insights into the effects of atVNS on memory performance and brain connectivity extending our knowledge of the biological mechanisms of bioelectronics in medicine.