Exploring the association of serum prolactin with serum glucose levels and clinical findings in a cohort of patients with early rheumatoid arthritis.

BACKGROUND: In the context of rheumatoid arthritis and its systemic inflammatory implications, there is an increasing interest in investigating the role of prolactin in the clinical and metabolic aspects of the disease. This study aimed to explore the potential links between serum prolactin levels, serum glucose levels, and the clinical manifestations of arthritis. METHODS: This exploratory, cross-sectional, observational study focused on women diagnosed with rheumatoid arthritis. The research involved assessing prolactin and blood glucose concentrations, alongside specific clinical traits such as disease-related inflammation, morning stiffness, and fatigue intensity. The presence of changes in serum prolactin (PRL) was initially compared among the groups based on disease activity intensity. Using a multinomial regression analysis, the study analyzed the impact of predetermined clinical and metabolic factors on various categories of prolactin concentration. RESULTS: Out of the 72 participants included in the study, hyperprolactinemia was detected in 9.1% of the sample. No differences in serum PRL were identified among the evaluated groups based on disease activity. Following multivariate analysis, no statistically significant differences were identified for the outcomes of inflammatory activity and morning stiffness within each PRL category when compared to the reference category for PRL. There was no increased likelihood of encountering blood glucose levels below 100 mg/dl among individuals with higher prolactin concentrations compared to those in the lowest prolactin category (OR 5.43, 95% CI 0.51-58.28). The presence of clinically significant fatigue revealed a higher likelihood of encountering this outcome among patients with intermediate PRL values (prolactin categories 7.76-10.35 with OR 5.18, 95% CI 1.01-26.38 and 10.36-15.29 with OR 6.25, 95% CI 1.2-32.51) when compared to the reference category. CONCLUSIONS: The study found no discernible correlation between prolactin concentrations and worse scores for inflammatory activity of the disease, nor between prolactin concentrations and serum glucose levels. The findings regarding fatigue should be approached with caution given the exploratory nature of this study.

Challenges in implementing treat-to-target in rheumatoid arthritis: a perspective from Brazilian rheumatologists.

BACKGROUND: Patient management in rheumatoid arthritis (RA) has evolved to a "treat-to-target" (T2T) approach, which entails intensive treatment and regular follow-up with the goal of achieving low levels of disease activity or clinical remission. Even though a T2T approach is endorsed by professional organizations and yields superior outcomes, its implementation remains incomplete. EVEREST (EleVatE care in RhEumatoid arthritiS with Treat-to-target) is a quality-improvement initiative designed to improve the widespread implementation of a personalized T2T strategy and enable patients with RA to reach their full potential for remission. We describe the Brazilian results from the Global T2T Survey, first part of the EVEREST program. METHODS: Between June and September 2022, we conducted an online survey targeting rheumatologists in Brazil. Our objective was to evaluate the barriers and knowledge gaps hindering the effective implementation of T2T strategies. To achieve this, we employed a set of multiple-choice questions specifically crafted to elicit responses categorized in a structured order. RESULTS: 166 rheumatologists participated in the survey, 51% of them with more than 21 years of experience in rheumatology. Regarding the perceived challenges in the management of RA in clinical practice, the highest percentage of agreement/strong agreement among the participants was related to the contradictory results of disease activity measures (60%). In terms of the main barriers to assess the disease activity in clinical practice, the lack of adherence to treatment and contradictory assessments between patient-reported outcomes and composite measures were indicated by 75% and 59% of the participants, respectively, as a moderate/serious barrier. The most frequently knowledge and skill gaps related to the management of RA pointed out by the participants were on the difficulty to assess patients' health literacy (54% stated to have no more than intermediate knowledge on standardized methods to assess it and 43% no more than intermediate skills on determining the level of health literacy of the patients). In general, the use of tools to support the management of RA patients in clinical practice was indicated to be unusual by the participants. Self-reflection questionnaires, patient education materials and treatment consideration checklists were pointed out as the least frequently used tools (85%, 64% and 62% of the participants stated to use them never, rarely, or only sometimes, respectively). CONCLUSIONS: Our findings indicate a greater need for design, selection, and uptake of practical strategies to further improve communication between healthcare providers and patients with RA, as well as for promoting well-informed, collaborative decision-making in their care.

Hydroxychloroquine is associated with lower seroconversion upon 17DD-Yellow fever primovaccination in patients with primary Sjögren's syndrome.

The present study aimed at investigating whether the hydroxychloroquine (HCQ) treatment would impact the neutralizing antibody production, viremia levels and the kinetics of serum soluble mediators upon planned 17DD-Yellow Fever (YF) primovaccination (Bio-Manguinhos-FIOCRUZ) of primary Sjögren's syndrome (pSS). A total of 34 pSS patients and 23 healthy controls (HC) were enrolled. The pSS group was further categorized according to the use of HCQ (HCQ and Non-HCQ). The YF-plaque reduction neutralization test (PRNT ≥1:50), YF viremia (RNAnemia) and serum biomarkers analyses were performed at baseline and subsequent time-points (Day0/Day3-4/Day5-6/Day7/Day14-D28). The pSS group showed PRNT titers and seropositivity rates similar to those observed for HC (GeoMean = 238 vs 440, p = .11; 82% vs 96%, p = .13). However, the HCQ subgroup exhibited lower seroconversion rates as compared to HC (GeoMean = 161 vs 440, p = .04; 69% vs 96%, p = .02) and Non-HQC (GeoMean = 161 vs 337, p = .582; 69% vs 94%, p = .049). No differences in YF viremia were observed amongst subgroups. Serum biomarkers analyses demonstrated that HCQ subgroup exhibited increased levels of CCL2, CXL10, IL-6, IFN-γ, IL1-Ra, IL-9, IL-10, and IL-2 at baseline and displayed a consistent increase of several biomarkers along the kinetics timeline up to D14-28. These results indicated that HCQ subgroup exhibited a deficiency in assembling YF-specific immune response elicited by 17DD-YF primovaccination as compared to Non-HCQ subgroup. Our findings suggested that hydroxychloroquine is associated with a decrease in the humoral immune response after 17DD-YF primovaccination.

Predictors of serious infections in rheumatoid arthritis-a prospective Brazilian cohort.

BACKGROUND: Infections increase mortality and morbidity and often limit immunosuppressive treatment in rheumatoid arthritis patients. OBJECTIVE: To analyze the occurrence of serious infections and the associated factors in a cohort of rheumatoid arthritis patients under real-life conditions. METHODS: We analyzed data from the REAL, a prospective observational study, that evaluated Brazilian RA patients, with clinical and laboratory data collected over a year. Univariate and multivariate analyses were performed from the adjustment of the logistic regression model Generalized Estimating Equations (GEE), with the primary outcome being the occurrence of serious infection, defined as need for hospitalization or use of intravenous antibiotics for its treatment. RESULTS: 841 patients were included with an average follow-up time of 11.2 months (SD 2.4). Eighty-nine serious infections occurred, corresponding to 13 infections per 100 patient-years. Pulmonary fibrosis, chronic kidney disease (CKD) and central nervous system disease increased the chances of serious infection by 3.2 times (95% CI: 1.5-6.9), 3.6 times (95% CI: 1.2-10.4) and 2.4 times (95% CI: 1.2-5.0), respectively. The use of corticosteroids in moderate doses increased the chances by 5.4 times (95% CI: 2.3-12.4), and for each increase of 1 unit in the health assessment questionnaire (HAQ), the chance increased 60% (95% CI: 20-120%). CONCLUSION: The use of corticosteroids at moderate doses increased the risk of serious infection in RA patients. Reduced functionality assessed by the HAQ and comorbidities were other important factors associated with serious infection in this cohort.

Impact of the COVID-19 Pandemic on People Living with Rheumatoid Arthritis: Experiences and Preferences in Accessing Healthcare Across Five Countries.

INTRODUCTION: The global coronavirus 2019 (COVID-19) pandemic created many challenges in healthcare provision. This study aimed to evaluate the global impact of the COVID-19 pandemic on people living with rheumatoid arthritis (RA). METHODS: The RA Narrative COVID-19 survey was conducted online among people with RA who resided in Brazil, Canada, France, Japan, and the US from August to September 2021. The survey examined disease management, healthcare access and experiences, and participant preferences for interactions with their doctor. RESULTS: Overall, 500 participants completed the survey: 100 each resided in Brazil, Canada, France, Japan, and the US. Emotional well-being was the aspect of disease management most reported to be negatively impacted by the pandemic (55% of participants); 'having more anxiety and/or stress' during the pandemic was the top factor that made controlling RA symptoms more difficult (49% of participants). In comparison, the top factor that made controlling RA symptoms easier was 'having a less busy schedule' (35% of participants). More participants had virtual appointments during versus pre-pandemic (53% vs. 13%, respectively) and participants were equally satisfied with the overall quality of care received via virtual and in-person appointments (76% of participants were 'satisfied' or 'very satisfied' with both). However, participants generally preferred in-person over virtual appointments, except for prescription refills, for which preferences were similar (39% vs. 36%, respectively). CONCLUSIONS: This survey suggests that the COVID-19 pandemic did negatively impact some aspects of disease management for people living with RA but had positive impacts on the utilization of virtual care. Although participants generally preferred in-person appointments, these results position virtual care as an appropriate means for routine follow-ups.

Elevated serum IL-6 levels predict treatment interruption in patients with moderate to severe psoriasis: a 6-year real-world cohort study.

BACKGROUND: Real-world, primary data on the treatment of psoriasis are scarce, especially concerning the role of soluble biomarkers as outcome predictors. OBJECTIVE: The authors evaluated the utility of Th1/Th17 serum cytokines along with clinical characteristics as predictors of drug survival in the treatment of psoriasis. METHODS: The authors consecutively included participants with moderate to severe psoriasis who were followed up for 6 years. Baseline interferon-α, tumor necrosis factor-α, and interleukin (IL)-2, IL-4, IL-6, IL-10, and IL-17A were measured using a cytometric bead array; clinical data were assessed. The authors calculated hazard ratios (HRs) for drug survival using a Cox proportional hazards model. RESULTS: The authors included 262 patients, most of whom used systemic immunosuppressants or biologics. In the multivariate model, poor quality of life measured by the Dermatology Life Quality Index (HR = 1.04; 95% CI 1.01‒1.07; p = 0.012) and elevated baseline IL-6 (HR = 1.99; 95% CI 1.29‒3.08; p = 0.002) were associated with treatment interruption. STUDY LIMITATIONS: The main limitation of any cohort study is the presence of confounders that could not be detected in clinical evaluation. CONCLUSIONS: Poor quality of life and elevated baseline serum IL-6 level predicted treatment interruption in patients with moderate to severe psoriasis. Although IL-6 is not the most important mediator of the inflammatory pathway in the skin environment, it is an interesting biomarker candidate for predicting psoriasis treatment response.

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.

New insights at the interface between leprosy and immune-mediated rheumatic diseases.

Leprosy is an infectious and contagious disease of slow evolution, triggered by Mycobacterium leprae. Arthritis is its third most common manifestation, after cutaneous and peripheral nerve involvement. Since musculoskeletal symptoms may be the initial presentation of the disease, it is important for health professionals to recognize its rheumatic manifestations for early diagnosis and appropriate treatment, especially in endemic areas. In addition, cases of leprosy have increased globally, notably in patients undergoing treatment with TNF-α blockers and due to the increase in migration and travel of people from developing countries to developed countries. This review proposes to discuss the main scenarios of mimicry of different rheumatic diseases by leprosy, as well as the role of immunosuppressive drugs used in rheumatology practice in the treatment of reactional states and in the risk of developing the infection.

Extra-articular manifestations of rheumatoid arthritis remain a major challenge: data from a large, multi-centric cohort.

INTRODUCTION: Although Rheumatoid Arthritis (RA) extra-articular manifestations (ExtRA) occurrence has been decreasing over time, they are still a major mortality risk factor for patients. OBJECTIVE: To determine the prevalence of ExtRA in a large cohort, and its association with demographic and clinical variables. METHOD: Cross-sectional and observational study, based on a multi-centric database from a prospective cohort, in which 11 public rheumatology centres enrolled RA patients (1987 ARA or 2010 ACR-EULAR). Data collection began in 08-2015, using a single online electronic medical record. Continuous variables were compared using Mann-Whitney U-test, and Fisher's exact test or chi-square test, as appropriate, were used for categorical variables. The level of significance was set at 5% (p < 0.05). RESULTS: 1115 patients were included: 89% women, age [mean ± SD] 58.2 ± 11.5 years, disease duration 14.5 ± 12.2 years, positive Rheumatoid Factor (RF, n = 1108) in 77%, positive anti-cyclic citrullinated peptide (ACPA, n = 477) in 78%. Regarding ExtRA, 334 occurrences were registered in 261 patients, resulting in an overall prevalence of 23.4% in the cohort. The comparison among ExtRA and Non-ExtRA groups shows significant higher age (p < 0.001), disease duration (p < 0.001), RF high titers (p = 0.018), Clinical Disease Activity index (CDAI) (p < 0.001), Disease Activity Index 28 (DAS 28) (p < 0.001), and Health Assessment Questionnaire (HAQ) (p < 0.001) in ExtRA group. Treatment with Azathioprine (p = 0.002), Etanercept (p = 0.049) Glucocorticoids (GC) ('p = 0.002), and non-steroidal anti-inflammatory drugs (NSAIDs) (p < 0.001) were more frequent in ExtRA group. CONCLUSIONS: ExtRA manifestations still show an expressive occurrence that should not be underestimated. Our findings reinforce that long-term seropositive disease, associated with significant disability and persistent inflammatory activity are the key factors related to ExtRA development.

Compared efficacy of rituximab, abatacept, and tocilizumab in patients with rheumatoid arthritis refractory to methotrexate or TNF inhibitors agents: a systematic review and network meta-analysis.

BACKGROUND: Our aim was to compare the efficacy of rituximab, tocilizumab, and abatacept in individuals with rheumatoid arthritis (RA) refractory to treatments with MTX or TNFi agents. METHODS: We searched 6 databases until January 2023 for phase 2-4 RCTs evaluating patients with RA refractory to MTX or TNFi therapy treated with rituximab, abatacept, and tocilizumab (intervention arm) compared to controls. Study data were independently assessed by two investigators. The primary outcome was considered as achieving ACR70 response. RESULTS: The meta-analysis included 19 RCTs, with 7,835 patients and a mean study duration of 1.2 years. Hazard ratios for achieving an ACR70 response at six months were not different among the bDMARDs, however, we found high heterogeneity. Three factors showing a critical imbalance among the bDMARD classes were identified: baseline HAQ score, study duration, and frequency of TNFi treatment in control arm. Multivariate meta-regression adjusted to these three factors were conducted for the relative risk (RR) for ACR70. Thus, heterogeneity was attenuated (I2 = 24%) and the explanatory power of the model increased (R2 = 85%). In this model, rituximab did not modify the chance of achieving an ACR70 response compared to abatacept (RR = 1.773, 95%CI 0.113-10.21, p = 0.765). In contrast, abatacept was associated with RR = 2.217 (95%CI 1.554-3.161, p < 0.001) for ACR70 compared to tocilizumab. CONCLUSION: We found high heterogeneity among studies comparing rituximab, abatacept, and tocilizumab. On multivariate metaregressions, if the conditions of the RCTs were similar, we estimate that abatacept could increase the chance of reaching an ACR70 response by 2.2-fold compared to tocilizumab.

Neuroimaging assessment of pediatric cerebral changes associated with SARS-CoV-2 infection during pregnancy.

Background: SARS-CoV-2 infection and perinatal neurologic outcomes are still not fully understood. However, there is recent evidence of white matter disease and impaired neurodevelopment in newborns following maternal SARS-CoV-2 infection. These appear to occur as a consequence of both direct viral effects and a systemic inflammatory response, with glial cell/myelin involvement and regional hypoxia/microvascular dysfunction. We sought to characterize the consequences of maternal and fetal inflammatory states in the central nervous system of newborns following maternal SARS-CoV-2 infection. Methods: We conducted a longitudinal prospective cohort study from June 2020 to December 2021, with follow-up of newborns born to mothers exposed or not exposed to SARS-CoV-2 infection during pregnancy. Brain analysis included data from cranial ultrasound scans (CUS) with grayscale, Doppler studies (color and spectral), and ultrasound-based brain elastography (shear-wave mode) in specific regions of interest (ROIs): deep white matter, superficial white matter, corpus callosum, basal ganglia, and cortical gray matter. Brain elastography was used to estimate brain parenchymal stiffness, which is an indirect quantifier of cerebral myelin tissue content. Results: A total of 219 single-pregnancy children were enrolled, including 201 born to mothers exposed to SARS-CoV-2 infection and 18 from unexposed controls. A neuroimaging evaluation was performed at 6 months of adjusted chronological age and revealed 18 grayscale and 21 Doppler abnormalities. Predominant findings were hyperechogenicity of deep brain white matter and basal ganglia (caudate nuclei/thalamus) and a reduction in the resistance and pulsatility indices of intracranial arterial flow. The anterior brain circulation (middle cerebral and pericallosal arteries) displayed a wider range of flow variation than the posterior circulation (basilar artery). Shear-wave US elastography analysis showed a reduction in stiffness values in the SARS-CoV-2 exposed group in all analyzed regions of interest, especially in the deep white matter elasticity coefficients (3.98 ± 0.62) compared to the control group (7.76 ± 0.77); p-value < 0.001. Conclusion: This study further characterizes pediatric structural encephalic changes associated with SARS-CoV-2 infection during pregnancy. The maternal infection has been shown to be related to cerebral deep white matter predominant involvement, with regional hyperechogenicity and reduction of elasticity coefficients, suggesting zonal impairment of myelin content. Morphologic findings may be subtle, and functional studies such as Doppler and elastography may be valuable tools to more accurately identify infants at risk of neurologic damage.

Panoramic snapshot of serum soluble mediator interplay in pregnant women with convalescent COVID-19: an exploratory study.

Introduction: SARS-CoV-2 infection during pregnancy can induce changes in the maternal immune response, with effects on pregnancy outcome and offspring. This is a cross-sectional observational study designed to characterize the immunological status of pregnant women with convalescent COVID-19 at distinct pregnancy trimesters. The study focused on providing a clear snapshot of the interplay among serum soluble mediators. Methods: A sample of 141 pregnant women from all prenatal periods (1st, 2nd and 3rd trimesters) comprised patients with convalescent SARS-CoV-2 infection at 3-20 weeks after symptoms onset (COVID, n=89) and a control group of pre-pandemic non-infected pregnant women (HC, n=52). Chemokine, pro-inflammatory/regulatory cytokine and growth factor levels were quantified by a high-throughput microbeads array. Results: In the HC group, most serum soluble mediators progressively decreased towards the 2nd and 3rd trimesters of pregnancy, while higher chemokine, cytokine and growth factor levels were observed in the COVID patient group. Serum soluble mediator signatures and heatmap analysis pointed out that the major increase observed in the COVID group related to pro-inflammatory cytokines (IL-6, TNF-α, IL-12, IFN-γ and IL-17). A larger set of biomarkers displayed an increased COVID/HC ratio towards the 2nd (3x increase) and the 3rd (3x to 15x increase) trimesters. Integrative network analysis demonstrated that HC pregnancy evolves with decreasing connectivity between pairs of serum soluble mediators towards the 3rd trimester. Although the COVID group exhibited a similar profile, the number of connections was remarkably lower throughout the pregnancy. Meanwhile, IL-1Ra, IL-10 and GM-CSF presented a preserved number of correlations (≥5 strong correlations in HC and COVID), IL-17, FGF-basic and VEGF lost connectivity throughout the pregnancy. IL-6 and CXCL8 were included in a set of acquired attributes, named COVID-selective (≥5 strong correlations in COVID and <5 in HC) observed at the 3rd pregnancy trimester. Discussion and conclusion: From an overall perspective, a pronounced increase in serum levels of soluble mediators with decreased network interplay between them demonstrated an imbalanced immune response in convalescent COVID-19 infection during pregnancy that may contribute to the management of, or indeed recovery from, late complications in the post-symptomatic phase of the SARS-CoV-2 infection in pregnant women.

High prevalence of mental disorder symptoms among medical and other health specialties residents during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic put healthcare professionals, including residents (postgraduate trainees of health professions), under intense physical and psychological stress, hence at risk for mental disorders. We evaluated the prevalence of mental disorders among healthcare residents during the pandemic. METHODS: From July to September 2020, residents in medicine and other healthcare specialties in Brazil were recruited. The participants completed electronic forms with validated questionnaires (DASS-21, PHQ-9, BRCS) to screen for depression, anxiety, and stress, and to evaluate resilience. Data on potential predisposing factors for mental disorders were also collected. Descriptive statistics, chi-squared, students t, correlation and logistic regression models were applied. The study received ethical approval, and all participants provided informed consent. RESULTS: We included 1313 participants (51.3% medical; 48.7% nonmedical) from 135 Brazilian hospitals; mean (SD) age: 27.8 (4.4) years; 78.2% females; 59.3% white race. Of all participants, 51.3%, 53.4% and 52.6% presented symptoms consistent with depression, anxiety, and stress, respectively; 61.9% showed low resilience. Nonmedical residents exhibited higher anxiety compared to medical residents (DASS-21 anxiety score, mean difference: 2.26; 95% CI: 1.15-3.37; p < 0.001). In multivariate analyses, having any pre-existent, nonpsychiatric chronic disease was associated with higher prevalence of symptoms indicative of depression (odds ratio, OR: 2.05; 95% CI: 1.47-2.85, on DASS-21 | OR: 2.26; 95% CI: 1.59-3.20, on PHQ-9), anxiety (OR: 2.07; 95% CI: 1.51-2.83, on DASS-21), and stress (OR: 1.53; 95% CI: 1.12-2.09, on DASS-21); other predisposing factors were identified; by contrast, high resilience (BRCS score) was protective against symptoms of depression (OR 0.82; 95% CI: 0.79-0.85, on DASS-21 | OR 0.85; 95% CI: 0.82-0.88, on PHQ-9), anxiety (OR 0.90; 95% CI: 0.87-0.93, on DASS-21), and stress (OR 0.88; 95% CI: 0.85-0.91, on DASS-21); p < 0.05 for all outcomes. CONCLUSIONS: We found a high prevalence of mental disorder symptoms among healthcare residents during COVID-19 pandemic in Brazil. Nonmedical residents exhibited higher levels of anxiety than medical ones. Some predisposing factors for depression, anxiety and stress among residents were identified.

Decreasing delays in the diagnosis and treatment of rheumatoid arthritis in Brazil: a nationwide multicenter observational study.

BACKGROUND: Management delays imply worse outcomes in rheumatoid arthritis (RA) and, therefore, should be minimized. We evaluated changes in diagnostic and treatment delays regarding RA in the last decades in Brazil. METHODS: Adults fulfilling the ACR/EULAR (2010) criteria for RA were assessed. Delays in diagnosis and treatment, and the frequencies of early management initiation within thresholds (windows of opportunity) of 3, 6, and 12 months from symptoms onset were evaluated. The Mann-Kendall trend test, chi-squared tests with Cramer's V effect sizes and analysis of variance were conducted. RESULTS: We included 1116 patients: 89.4% female, 56.8% white, mean (SD) age 57.1 (11.5) years. A downward trend was found in diagnostic (tau = - 0.677, p < 0.001) and treatment (tau = - 0.695, p < 0.001) delays from 1990 to 2015. The frequency of early management increased throughout the period, with ascending effect sizes across the 3-, 6-, and 12-month windows (V = 0.120, 0.200 and 0.261, respectively). Despite all improvements, even in recent years (2011-2015) the diagnostic and treatment delays still remained unacceptably high [median (IQR): 8 (4-12) and 11 (5-17) months, respectively], with only 17.2% of the patients treated within the shortest, 3-month window. CONCLUSION: The delays in diagnosis and treatment of RA decreased during the last decades in Brazil. Improvements (effect sizes) were greater at eliminating extreme delays (≥ 12 months) than in attaining really short management windows (≤ 3 months). Very early treatment was still an unrealistic goal for most patients with RA.

Unbalanced networks and disturbed kinetics of serum soluble mediators associated with distinct disease outcomes in severe COVID-19 patients.

The present study applied distinct models of descriptive analysis to explore the integrative networks and the kinetic timeline of serum soluble mediators to select a set of systemic biomarkers applicable for the clinical management of COVID-19 patients. For this purpose, a total of 246 participants (82 COVID-19 and 164 healthy controls - HC) were enrolled in a prospective observational study. Serum soluble mediators were quantified by high-throughput microbeads array on hospital admission (D0) and at consecutive timepoints (D1-6 and D7-20). The results reinforce that the COVID-19 group exhibited a massive storm of serum soluble mediators. While increased levels of CCL3 and G-CSF were associated with the favorable prognosis of non-mechanical ventilation (nMV) or discharge, high levels of CXCL10 and IL-6 were observed in patients progressing to mechanical ventilation (MV) or death. At the time of admission, COVID-19 patients presented a complex and robust serum soluble mediator network, with a higher number of strong correlations involving IFN-γ, IL-1Ra and IL-9 observed in patients progressing to MV or death. Multivariate regression analysis demonstrates the ability of serum soluble mediators to cluster COVID-19 from HC. Ascendant fold change signatures and the kinetic timeline analysis further confirmed that the pairs "CCL3 and G-CSF" and "CXCL10 and IL-6" were associated with favorable or poor prognosis, respectively. A selected set of systemic mediators (IL-6, IFN-γ, IL-1Ra, IL-13, PDGF and IL-7) were identified as putative laboratory markers, applicable as complementary records for the clinical management of patients with severe COVID-19.

Negative impact of SARS-CoV-2 infection in acute coronary syndrome mortality in a Latin American cohort study.

Purpose: COVID-19 infection has been associated with a high risk of complications and death among patients with acute coronary syndrome (ACS). However, there is little information on the simultaneous involvement in Latin American countries. Methods: In the period between May 2020 and February 2021, an observational, longitudinal, prospective cohort study with two parallel branches was conducted in private and public hospitals in Brasilia, Brazil, including patients with ACS with and without a positive SARS-CoV-2 test result during hospitalization. Results: A total of 149 patients with ACS were included (75 with COVID-19 and 74 controls). Patients with COVID-19 exhibited an average of 62 years of age, 57% men, 40% diabetics, 67% hypertensive, 48% had an ACS with ST-segment elevation, Killip I was predominant, a low Syntax Score in 72%, with an average Grace Score of 117, and a length of hospitalization of 43 days in average. The control branch was similar in clinical characteristics, except for a lower proportion of ST-segment elevation ACS (16%, p < 0.01) and a higher incidence of arrhythmias (8 vs. 20 %, p = 0.03). Using the Cox regression method of analysis of covariates collected in the study, it was identified that patients with COVID-19 had a risk of death 2.34 times higher than patients without COVID-19 (p = 0.049). Conclusion: In this study conducted in a Latin American capital, SARS-CoV-2 infection predicted a higher chance of death in patients admitted with ACS, which is a finding that reinforces the need for greater care when diseases develop in overlapping ways.

Cerebrospinal fluid analysis of pregnant women at early stages of COVID-19.

OBJECTIVE: To determine the presence or absence of SARS-CoV-2 in the cerebrospinal fluid of pregnant women at early stages of COVID-19. MATERIALS AND METHODS: We conducted a prospective observational study with pregnant women undergoing cesarean section and real-time polymerase chain reaction to SARS-CoV-2 was performed in the cerebrospinal fluid in the early stages of COVID-19. RESULTS: Fourteen pregnant women, whose COVID-19 symptoms started between four to 18 days prior to delivery, were included. Eleven of the women reported anosmia, dysgeusia, and headaches and there were two fatal cases. SARS-Cov-2 was not present in the cerebrospinal fluid of these COVID-19 patients with early neurological symptoms, even in severe cases. CONCLUSION: Our study suggests that peripheric cell damage and parainfectious phenomena may predominate over direct central nervous system injury in the pathophysiology of COVID-19 related early neurological symptoms on pregnant women.

How Did Patients Living With Immune-Mediated Rheumatic Diseases Face the Beginning of the COVID-19 Pandemic in Brazil? Results of the COnVIDa Study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has brought additional burden to patients living with immune-mediated rheumatic diseases (IMRDs), especially at the beginning of 2020, for which information for this population is lacking. METHODS: COnVIDa is a cross-sectional study on patients with IMRD from all regions of Brazil who were invited to answer a specific and customized Web questionnaire about how they were facing the COVID-19 pandemic, especially focusing on health care access, use of medications, and patient-reported outcomes related to IMRD activity. The questionnaire was applied from June 1 to 30, 2020. RESULTS: In total, 1722 of 2576 patients who answered the Web questionnaire were included in the final analysis. Participants were most frequently women, 56% were between 31 and 50 years old, and most (55%) has private health insurance. The most commonly reported IMRD was rheumatoid arthritis (39%), followed by systemic lupus erythematosus (28%). During the study period, 30.7% did not have access to rheumatology consultations, and 17.6% stopped chronic medications. Telemedicine was reported in 44.8% of patients. CONCLUSION: COnVIDa demonstrated a negative impact on health care access and treatment maintenance of patients living with IMRD during the COVID-19 pandemic. However, it also presented an uptake of telemedicine strategies. Data presented in this study may assist future coping policies.

Impact of COVID-19 on the mental health of public university hospital workers in Brazil: A cohort-based analysis of 32,691 workers.

BACKGROUND: In early 2020, the COVID-19 pandemic paralyzed the world and exposed the fragility of health systems in the face of mass illness. Health professionals became protagonists, fulfilling their mission at the risk of physical and mental illness. The study aimed to evaluate absenteeism indirectly related to SARS-CoV-2 infection in a large population of health care professionals. METHODS: An observational longitudinal repeated measures study was performed, including workers linked to 40 public university hospitals in Brazil. All causes of absenteeism were analyzed, focusing on those not directly attributed to COVID-19. Results for the same population were compared over two equivalent time intervals: prepandemic and during the pandemic. FINDINGS: A total of 32,691 workers were included in the study, with health professionals comprising 82.5% of the sample. Comparison of the periods before and during the pandemic showed a 26.6% reduction in work absence for all causes, except for COVID-19 and mental health-related absence. Concerning work absence related to mental health, the odds ratio was 39.0% higher during the pandemic. At the onset of the pandemic, there was an increase in absenteeism (all causes), followed by a progressive reduction until the end of the observation period. INTERPRETATION: Work absence related to mental illness among health care professionals increased during the COVID-19 pandemic, highlighting the need for health care managers to prioritize and implement support strategies to minimize absenteeism.