Factors associated with hospitalizations for Covid-19 in patients with rheumatoid arthritis: data from the Reumacov Brazil registry.

BACKGROUND: Patients using immunosuppressive drugs may have unfavorable results after infections. However, there is a lack of information regarding COVID-19 in these patients, especially in patients with rheumatoid arthritis (RA). Therefore, the aim of this study was to evaluate the risk factors associated with COVID-19 hospitalizations in patients with RA. METHODS: This multicenter, prospective cohort study is within the ReumaCoV Brazil registry and included 489 patients with RA. In this context, 269 patients who tested positive for COVID-19 were compared to 220 patients who tested negative for COVID-19 (control group). All patient data were collected from the Research Electronic Data Capture database. RESULTS: The participants were predominantly female (90.6%) with a mean age of 53 ± 12 years. Of the patients with COVID-19, 54 (20.1%) required hospitalization. After multiple adjustments, the final regression model showed that heart disease (OR = 4.61, 95% CI 1.06-20.02. P < 0.001) and current use of glucocorticoids (OR = 20.66, 95% CI 3.09-138. P < 0.002) were the risk factors associated with hospitalization. In addition, anosmia was associated with a lower chance of hospitalization (OR = 0.26; 95% CI 0.10-0.67, P < 0.005). CONCLUSION: Our results demonstrated that heart disease and the use of glucocorticoids were associated with a higher number of hospital admissions for COVID-19 in patients with RA. TRIAL REGISTRATION: Brazilian Registry of Clinical Trials - RBR-33YTQC.

A Review of Metabolomic Profiling in Rheumatoid Arthritis: Bringing New Insights in Disease Pathogenesis, Treatment and Comorbidities.

Metabolomic analysis provides a wealth of information that can be predictive of distinctive phenotypes of pathogenic processes and has been applied to better understand disease development. Rheumatoid arthritis (RA) is an autoimmune disease with the establishment of chronic synovial inflammation that affects joints and peripheral tissues such as skeletal muscle and bone. There is a lack of useful disease biomarkers to track disease activity, drug response and follow-up in RA. In this review, we describe potential metabolic biomarkers that might be helpful in the study of RA pathogenesis, drug response and risk of comorbidities. TMAO (choline and trimethylamine oxide) and TCA (tricarboxylic acid) cycle products have been suggested to modulate metabolic profiles during the early stages of RA and are present systemically, which is a relevant characteristic for biomarkers. Moreover, the analysis of lipids such as cholesterol, FFAs and PUFAs may provide important information before disease onset to predict disease activity and treatment response. Regarding therapeutics, TNF inhibitors may increase the levels of tryptophan, valine, lysine, creatinine and alanine, whereas JAK/STAT inhibitors may modulate exclusively fatty acids. These observations indicate that different disease modifying antirheumatic drugs have specific metabolic profiles and can reveal differences between responders and non-responders. In terms of comorbidities, physical impairment represented by higher fatigue scores and muscle wasting has been associated with an increase in urea cycle, FFAs, tocopherols and BCAAs. In conclusion, synovial fluid, blood and urine samples from RA patients seem to provide critical information about the metabolic profile related to drug response, disease activity and comorbidities.

Factors associated with hospitalizations for Covid-19 in patients with rheumatoid arthritis: data from the Reumacov Brazil registry

Abstract Background: Patients using immunosuppressive drugs may have unfavorable results after infections. However, there is a lack of information regarding COVID 19 in these patients, especially in patients with rheumatoid arthritis (RA). Therefore, the aim of this study was to evaluate the risk factors associated with COVID 19 hospitalizations in patients with RA. Methods: This multicenter, prospective cohort study is within the ReumaCoV Brazil registry and included 489 patients with RA. In this context, 269 patients who tested positive for COVID 19 were compared to 220 patients who tested negative for COVID 19 (control group). All patient data were collected from the Research Electronic Data Capture database. Results: The participants were predominantly female (90.6%) with a mean age of 53 ±12 years. Of the patients with COVID 19, 54 (20.1%) required hospitalization. After multiple adjustments, the final regression model showed that heart disease (OR =4.61, 95% CI 1.06-20.02. P < 0.001) and current use of glucocorticoids (OR =20.66, 95% CI 3.09-138. P < 0.002) were the risk factors associated with hospitalization. In addition, anosmia was associated with a lower chance of hospitalization (OR =0.26; 95% CI 0.10-0.67, P < 0.005). Conclusion: Our results demonstrated that heart disease and the use of glucocorticoids were associated with a higher number of hospital admissions for COVID 19 in patients with RA. Trial registration: Brazilian Registry of Clinical Trials RBR 33YTQC.

Practical screening tools for sarcopenia in patients with systemic sclerosis.

INTRODUCTION: In view of the method of diagnosing sarcopenia being complex and considered to be difficult to introduce into routine practice, the European Working Group on Sarcopenia in Older People (EWGSOP) recommends the use of the SARC-F questionnaire as a way to introduce assessment and treatment of sarcopenia into clinical practice. Only recently, some studies have turned their attention to the presence of sarcopenia in systemic sclerosis (SSc).There is no data about performance of SARC-F and other screening tests for sarcopenia in this population. OBJECTIVE: To compare the accuracy of SARC-F, SARC-CalF, SARC-F+EBM, and Ishii test as screening tools for sarcopenia in patients with SSc. METHODS: Cross-sectional study of 94 patients with SSc assessed by clinical and physical evaluation. Sarcopenia was defined according to the revised 2019 EWGSOP diagnostic criteria (EWGSOP2) with assessments of dual-energy X-ray absorptiometry, handgrip strength, and short physical performance battery (SPPB). As case finding tools, SARC-F, SARC-CalF, SARC-F+EBM and Ishii test were applied, including data on calf circumference, body mass index, limitations in strength, walking ability, rising from a chair, stair climbing, and self reported number of falls in the last year. The screening tests were evaluated through receiver operating characteristic (ROC) curves. Standard measures of diagnostic accuracy were computed using the EWGSOP2 criteria as the gold standard for diagnosis of sarcopenia. RESULTS: Sarcopenia was identified in 15 (15.9%) patients with SSc by the EWGSOP2 criteria. Area under the ROC curve of SARC-F screening for sarcopenia was 0.588 (95% confidence interval (CI) 0.420-0.756, p = 0.283). The results of sensitivity, specificity, positive likelihood ratio (+LR), negative likelihood ratio (-LR) and diagnostic Odds Ratio (DOR) with the EWGSOP2 criteria as the gold standard were 40.0% (95% CI, 19.8-64.2), 81.0% (95% CI, 71.0-88.1), 2.11 (95% CI, 0.98-4.55), 0.74 (95% CI, 0.48-1.13) and 2.84 (95% CI, 0.88-9.22), respectively. SARC-CalF and SARC-F+EBM showed better sensitivity (53.3%, 95% CI 30.1-75.2 and 60.0%, 95% CI 35.7-80.2, respectively) and specificity (84.8%, 95% CI 75.3-91.1 and 86.1%, 95% CI 76.8-92.0, respectively) compared with SARC-F. The best sensitivity was obtained with the Ishii test (86.7%, 95% CI 62.1-96.3), at the expense of a small loss of specificity (73.4%, 95% CI 62.7-81.9). Comparing the ROC curves, SARC-F performed worse than SARC-CalF, SARC-F+EBM and Ishii test as a sarcopenia screening tool in this population (AUCs 0.588 vs. 0.718, 0.832, and 0.862, respectively). Direct comparisons between tests revealed differences only between SARC-F and Ishii test for sensitivity (p = 0.013) and AUC (p = 0.031). CONCLUSION: SARC-CalF, SARC-F+EBM, and Ishii test performed better than SARC-F alone as screening tools for sarcopenia in patients with SSc. Considering diagnostic accuracy and feasibility aspects, SARC-F+EBM seems to be the most suitable screening tool to be adopted in routine care of patients with SSc.

Coagulase-negative staphylococci in outpatient routines: the implications of switching from CLSI to BrCAST/EUCAST guidelines.

Coagulase-negative staphylococci (CoNS) are frequently isolated in clinical specimens and are important reservoirs of resistance genes. In 2019, the Brazilian government set the BrCAST/EUCAST (Brazilian Committee on Antimicrobial Susceptibility Testing) guidelines as the national standard, resulting in changes in the interpretation of CoNS susceptibility tests. From outpatients, disk-diffusion susceptibility of 65 CoNS cultures were evaluated and compared using classification criteria from both CLSI and BrCAST/EUCAST. The isolates were identified using matrix assisted laser desorption ionization-time of flight (MALDI-TOF), and the presence of the mecA gene was determined. The most prevalent species were Staphylococcus saprophyticus (32.3%), S. haemolyticus (18.5%), and S. epidermidis (9.2%). Almost perfect agreement was seen between the guidelines, except concerning oxacillin and gentamicin, and the prevalence of multidrug resistant isolates increased with the use of BrCAST/EUCAST. Of all, 15 (23.1%) isolates, mainly S. epidermidis and S. haemolyticus, were positive for the mecA gene, and only three were detected when using CLSI or BrCAST/EUCAST disk-diffusion screening. This, using either guideline, could reveal the difficulty of determining oxacillin resistance. Using warning zones or molecular methods might well be indicated for CoNS. In conclusion, adoption of the BrCAST/EUCAST guidelines will result in certain artificial changes in epidemiological susceptibility profiles, and clinicians and institutions should be aware of the possible implications.

A evolução do diagnóstico da doença mista do tecido conjuntivo / Evolution of the diagnosis of mixed connective tissue disease

A Doença Mista do Tecido Conjuntivo (DMTC) é uma doença autoimune crônica composta por um misto de quatro doenças: Lúpus Eritematoso Sistêmico, Esclerose Sistêmica, Dermatomiosite/Polimiosite e Artrite Reumatoide. Por se tratar de uma combinação de doenças autoimunes o diagnóstico é bastante complexo. Atualmente existem quatro combinações sugeridas por diferentes autores para a realização de um diagnóstico preciso, são eles: Kasukawa, Alarcón-Segovia e Villareal, Kahn e Appeboom e Sharp. Desde a sua descoberta em 1972 por Sharp, passaram-se 46 anos e desta forma o objetivo desta revisão foi verificar a evolução do diagnóstico da DMTC desde a sua descoberta até a atualidade. Para isso utilizou-se sites de busca PUBMED e SCIELO. Por se tratar de uma doença autoimune que leva ao desenvolvimento de um quadro inflamatório crônico utilizou-se a ferramenta STRING que permite a análise da interação de proteínas. Até a presente data, não existe um consenso de qual critério deve ser usado para o diagnóstico correto e eficiente desta doença. A baixa relação de interações observadas a partir da ferramenta STRING demonstra que ainda não existem dados suficientes na literatura para que a ligação entre proteínas marcadoras e a DTMC possa ser estabelecida. (AU)

Mixed connective tissue disease (MCTD) is a chronic autoimmune disorder consisting of a mixture of four diseases: systemic lupus erythematosus, systemic sclerosis, dermatomyositis/polymyositis, and rheumatoid arthritis. Because it is a combination of different autoimmune disorders its diagnosis is quite complex. Currently there are four combinations suggested by the following authors to establish an accurate diagnosis: Kasukawa, Alarcón-Segovia & Villareal, Kahn, and Appeboom & Sharp. It has been 46 years since Sharp reported the disease in 1972 and thus the purpose of this review was to investigate the evolution of the diagnosis of MCTD since then. PubMed and SciELO databases were used for this investigation. Because MCTD is an autoimmune disease that leads to the development of a chronic inflammatory condition, the STRING tool was used to allow the analysis of protein interaction. To date, there is no consensus as to what criterion should be used for a correct and efficient diagnosis of this disease. The low ratio of interactions observed from the STRING tool demonstrates that there is not yet enough data in the literature for establishing the binding between marker proteins and MCTD. (AU)

Prevalência de Streptococcus agalactiae em gestantes da Grande Porto Alegre, RS: relato de caso / Prevalence of Streptococcus agalactiae in pregnant women of Porto Alegre, RS: case report

O Streptococcus agalactiae é um coco Gram-positivo, beta-hemolítico que faz parte da microbiota de membranas mucosas, colonizando, principalmente, o trato intestinal e o genitourinário. A identificação no trato anogenital das gestantes é de importância para asaúde da mulher e do feto, visto que esse microrganismo pode causar infecções neonatais graves, septicemia, pneumonia e meningite neonatal, assim como causar infecção no organismo materno e comprometer a evolução da gestação. Cento e quarenta e quatrogestantes foram submetidas à coleta de secreção vaginal e perianal para cultura em meio Stuart. A amostra da secreção vaginal foi inoculada em agar sangue e a amostra da secreção anal em meio azida, as quais foram incubadas a 37°C, por 24 horas, seguindo-se o teste de CAMP. Foi possível verificar a alta frequência de colonização por S.agalactiae, neste estudo (40%), principalmente em pacientes entre a 34ª e a 37ª semanas de gestação (64%), o que ressalta a importância da inclusão da cultura de secreção vaginal e perianal para pesquisa desse microrganismo nos exames pré-natais...

Anti-proliferative effect of the gastrin-release peptide receptor antagonist RC-3095 plus temozolomide in experimental glioblastoma models.

Malignant gliomas have a dismal prognosis despite multi-modality treatments like neurosurgical resection, radiation therapy and chemotherapy. Evidence has indicated that gastrin-releasing peptide (GRP) and its receptor (GRPR) play a role in the development of a variety of cancers including gliomas. In the present study, we investigated the effects of RC-3095, a selective GRPR antagonist, alone or in combination with temozolomide (TMZ), a DNA alkylating agent, in in vitro and in vivo experimental rat C6 glioma models. Cellular proliferation was significantly reduced by all treatments with the combined administration of TMZ and RC-3095 being the most effective treatment. In in vivo experiments, the control group displayed the largest tumors (52 +/- 15.5 mm(3)), whereas RC-3095 reduced the tumor size, with the most significant effect at the dose of 0.3 mg/kg (21 +/- 9.7 mm(3)). The combined therapy produced further reduction in tumor size (10 +/- 7.5 mm(3)). Our results show that the combination of RC-3095 with TMZ produced an important reduction in in vitro and in vivo glioma growth therefore making RC-3095 a candidate drug to potentiate the effects of the DNA alkylating agent TMZ in the treatment of glioma.

Gastrin-releasing peptide receptors regulate proliferation of C6 Glioma cells through a phosphatidylinositol 3-kinase-dependent mechanism.

Gastrin-releasing peptide (GRP) has been proposed as a major growth factor in brain tumors, and GRP receptor (GRPR) antagonists show antiproliferative effects in experimental gliomas. However, the underlying molecular events downstream of GRPR activation remain poorly understood. In the present study, we examined the role of the GRPR in regulating proliferation of glioma cells in vitro and its possible interaction with the phosphatidylinositol 3-kinase (PI3K) signaling pathway. Expression of GRPR mRNA and protein in C6, U-87MG, and U-373MG glioma cells was analyzed by reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry. Proliferation of C6 and U-87MG, but not U-373MG cells was significantly inhibited by the GRPR antagonist RC-3095, whereas the GRPR agonist bombesin (BB) significantly enhanced proliferation of C6 cells. The BB-induced stimulatory effect on cell proliferation was prevented by either RC-3095 or the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002. Our results provide the first evidence that the GRPR regulates proliferation of C6 glioma cells and suggest that PI3K is required for GRPR-mediated stimulation of glioma growth.