Compartmentalized Regulation of Pulmonary and Systemic Inflammation in Critical COVID-19 Patients.

Critical COVID-19 has been associated with altered patterns of cytokines. Distinct inflammatory processes in systemic and pulmonary sites have been reported, but studies comparing these two sites are still scarce. We aimed to evaluate the profile of pulmonary and systemic cytokines and chemokines in critically ill COVID-19 patients. Levels of cytokines and chemokines were measured in plasma samples and minibronchoalveolar lavage of critical COVID-19 patients within 48 h and 5-8 days after intubation. Distinct inflammatory processes were observed in the lungs and blood, which were regulated separately. Survivor patients showed higher lung cytokine levels including IFN-γ, IL-2, IL-4, G-CSF, and CCL4, while nonsurvivors displayed higher levels in the blood, which included IL-6, CXCL8, CXCL10, CCL2, and CCL4. Furthermore, our findings indicate that high TNF and CXCL8 levels in the mini-BAL were associated with better lung oxygen exchange capacity, whereas high levels of IFN-γ in plasma were associated with worse lung function, as measured using the PaO2/FiO2 ratio. These results suggest that a robust and localized inflammatory response in the lungs is protective and associated with survival, whereas a systemic inflammatory response is detrimental and associated with mortality in critical COVID-19.

Morphofunctional analysis of fibroblast-like synoviocytes in human rheumatoid arthritis and mouse collagen-induced arthritis.

BACKGROUND: Fibroblast-like synoviocytes (FLS) play a prominent role in rheumatoid synovitis and degradation of the extracellular matrix through the production of inflammatory cytokines and metalloproteinases (MMPs). Since animal models are frequently used for elucidating the disease mechanism and therapeutic development, it is relevant to study the ultrastructural characteristics and functional responses in human and mouse FLS. The objective of the study was to analyze ultrastructural characteristics, Interleukin-6 (IL-6) and Metalloproteinase-3 (MMP-3) production and the activation of intracellular pathways in Fibroblast like synoviocytes (FLS) cultures obtained from patients with rheumatoid arthritis (RA) and from mice with collagen-induced arthritis (CIA). METHODS: FLSs were obtained from RA patients (RA-FLSs) (n = 8) and mice with CIA (CIA-FLSs) (n = 4). Morphology was assessed by transmission and scanning electron microscopy. IL-6 and MMP-3 production was measured by ELISA, and activation of intracellular signaling pathways (NF-κB and MAPK: p-ERK1/2, p-P38 and p-JNK) was measured by Western blotting in cultures of RA-FLSs and CIA-FLSs stimulated with tumor necrosis factor-alpha (TNF-α) and IL-1ß. RESULTS: RA-FLS and CIA-FLS cultures exhibited rich cytoplasm, rough endoplasmic reticula and prominent and well-developed Golgi complexes. Transmission electron microscopy demonstrated the presence of lamellar bodies, which are cytoplasmic structures related to surfactant production, in FLSs from both sources. Increased levels of pinocytosis and numbers of pinocytotic vesicles were observed in RA-FLSs (p < 0.05). Basal production of MMP-3 and IL-6 was present in RA-FLSs and CIA-FLSs. Regarding the production of MMP-3 and IL-6 and the activation of signaling pathways, the present study demonstrated a lower response to IL-1ß by CIA-FLSs than by RA-FLSs. CONCLUSION: This study provides a comprehensive understanding of the biology of RA-FLS and CIA-FLS. The differences and similarities in ultrastructural morphology and important inflammatory cytokines shown, contribute to future in vitro studies using RA-FLS and CIA-FLS, in addition, they indicate that the adoption of CIA-FLS for studies should take careful and be well designed, since they do not completely resemble human diseases.

Dysfunctional phenotype of systemic and pulmonary regulatory T cells associate with lethal COVID-19 cases.

Severe cases of COVID-19 present hyperinflammatory condition that can be fatal. Little is known about the role of regulatory responses in SARS-CoV-2 infection. In this study, we evaluated the phenotype of regulatory T cells in the blood (peripheral blood mononuclear cell) and the lungs (broncho-alveolar) of adult patients with severe COVID-19 under invasive mechanical ventilation. Our results show important dynamic variation on Treg cells phenotype during COVID-19 with changes in number and functional parameters from the day of intubation (Day 1 of intensive care unit admission) to Day 7. We observed that compared with surviving patients, non-survivors presented lower numbers of Treg cells in the blood. In addition, lung Tregs of non-survivors also displayed higher PD1 and lower FOXP3 expressions suggesting dysfunctional phenotype. Further signs of Treg dysregulation were observed in non-survivors such as limited production of IL-10 in the lungs and higher production of IL-17A in the blood and in the lungs, which were associated with increased PD1 expression. These findings were also associated with lower pulmonary levels of Treg-stimulating factors like TNF and IL-2. Tregs in the blood and lungs are profoundly dysfunctional in non-surviving COVID-19 patients.

Morphofunctional analysis of fibroblast-like synoviocytes in human rheumatoid arthritis and mouse collagen-induced arthritis

Abstract Background Fibroblast-like synoviocytes (FLS) play a prominent role in rheumatoid synovitis and degradation of the extracellular matrix through the production of inflammatory cytokines and metalloproteinases (MMPs). Since animal models are frequently used for elucidating the disease mechanism and therapeutic development, it is relevant to study the ultrastructural characteristics and functional responses in human and mouse FLS. The objective of the study was to analyze ultrastructural characteristics, Interleukin-6 (IL-6) and Metalloproteinase-3 (MMP-3) production and the activation of intracellular pathways in Fibroblast like synoviocytes (FLS) cultures obtained from patients with rheumatoid arthritis (RA) and from mice with collagen-induced arthritis (CIA). Methods FLSs were obtained from RA patients (RA-FLSs) (n = 8) and mice with CIA (CIA-FLSs) (n = 4). Morphology was assessed by transmission and scanning electron microscopy. IL-6 and MMP-3 production was measured by ELISA, and activation of intracellular signaling pathways (NF-κB and MAPK: p-ERK1/2, p-P38 and p-JNK) was measured by Western blotting in cultures of RA-FLSs and CIA-FLSs stimulated with tumor necrosis factor-alpha (TNF-α) and IL-1β. Results RA-FLS and CIA-FLS cultures exhibited rich cytoplasm, rough endoplasmic reticula and prominent and well- developed Golgi complexes. Transmission electron microscopy demonstrated the presence of lamellar bodies, which are cytoplasmic structures related to surfactant production, in FLSs from both sources. Increased levels of pinocytosis and numbers of pinocytotic vesicles were observed in RA-FLSs (p < 0.05). Basal production of MMP-3 and IL-6 was present in RA-FLSs and CIA-FLSs. Regarding the production of MMP-3 and IL-6 and the activation of signaling pathways, the present study demonstrated a lower response to IL-1β by CIA-FLSs than by RA-FLSs. Conclusion This study provides a comprehensive understanding of the biology of RA-FLS and CIA-FLS. The differences and similarities in ultrastructural morphology and important inflammatory cytokines shown, contribute to future in vitro studies using RA-FLS and CIA-FLS, in addition, they indicate that the adoption of CIA-FLS for studies should take careful and be well designed, since they do not completely resemble human diseases.

Performance of High Mobility Protein Group 1 and Interleukin-6 as Predictors of Outcomes Resulting from Variceal Bleeding in Patients with Advanced Chronic Liver Disease.

Variceal bleeding is a serious complication in cirrhotic patients and is related to increased expression of inflammatory mediators that accentuate circulatory dysfunction. The study aims to evaluate the performance of high mobility protein group 1 (HMG1) and interleukin-6 (IL-6) as predictors of acute kidney injury (AKI), infection and death in these patients. Fifty patients who were diagnosed with advanced chronic liver disease with variceal bleeding were included. The mean age was 52.8 ± 10.8 years, and 33 (66%) were male. Twenty-one (42%) patients were classified as Child-Pugh C, 21 (42%) Child-Pugh B and 8 (16%) Child-Pugh A. The mean HMG1 serum level was 2872.36 pg/mL ± 2491.94, and the median IL-6 serum level was 47.26 pg/mL (0-1102.4). In AKI, the serum level of HMG1 that performed best on the ROC curve was 3317.9 pg/mL. The IL-6 serum level was not associated with AKI. HMG1 and IL-6 cut-off values that better predicted infection were 3317.9 pg/mL and 72.9 pg/mL, and for mortality, the values were 2668 pg/mL and 84.5 pg/mL, respectively. In multivariate analysis, the variables that were associated with AKI and infection outcomes were model for end-stage liver disease and HMG1. Infections were related to the risk of death. Clinical and laboratory variables related to the outcomes were identified. Serum levels of HMG1 were associated with AKI and infection and had good performance in the ROC curve. IL-6 levels were not maintained in logistic regression outcomes but had good performance in infection and death outcomes. Such data will be useful for comparisons and possible future validations.

Lung Ultrasound Can Predict the Clinical Course and Severity of COVID-19 Disease.

Coronavirus disease 2019 (COVID-19) compromises the lung in large numbers of people. The development of minimally invasive methods to determine the severity of pulmonary extension is desired. This study aimed to describe the characteristics of sequential lung ultrasound and to test the prognostic usefulness of this exam in a group of patients admitted to the hospital with COVID-19. We prospectively evaluated patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection admitted to our hospital between April and August 2020. Bedside lung ultrasound exams were performed at three time points: at inclusion in the study, after 48 h and on the seventh day of follow-up. Lung ultrasound scores were quantified according to the aeration loss in each of eight zones scanned. Sixty-six participants were included: 42 (63.6%) in the intensive care unit and 24 (36.3%) in the ward. Lung ultrasound scores were higher in participants admitted to the intensive care unit than in those admitted to the ward at the time of inclusion (16 [13-17] vs. 10 [4-14], p < 0.001), after 48 h (15.5 [13-17] vs. 12.5 [8.2-14.7], p = 0.001) and on the seventh day (16 [14-17] vs. 7 [4.5-13.7], p < 0.001) respectively. Lung ultrasound score measured at the time of inclusion in the study was independently associated with the need for admission to the intensive care unit (odds ratio = 1.480; 95% confidence interval, 1.093-2.004; p = 0.011) adjusted by the Sequential Organ Failure Assessment score.

Clinical Frailty Scale em idosos atendidos no Serviço Hospitalar de Emergência: a fragilidade basal é um bom preditor de mortalidade em 90 dias? / Clinical Frailty Scale in older adults admitted at Emergency Department: is baseline frailty a good predictor of Ninety-Day Mortality?

Resumo Objetivo Avaliar a capacidade da Clinical Frailty Scale (CFS) em predizer a mortalidade em até 90 dias e outros desfechos desfavoráveis em idosos admitidos em um Serviço Hospitalar de Emergência (SHE). Método Estudo de coorte prospectivo que incluiu idosos admitidos e que permaneceram por pelo menos uma noite no SHE de um hospital público terciário. O grau de fragilidade basal foi avaliado através da CFS e sua pontuação, o preditor estudado, por meio da curva Receiver Operator Characteristics (ROC). Analisou-se como desfecho primário a mortalidade em 90 dias. Considerou-se como desfechos secundários: mortalidade em 180 dias, declínio funcional, readmissão no SHE, reinternação e necessidade de atenção domiciliar. Resultados 206 participantes foram incluídos. Dos 127 idosos frágeis, 40 (31,5%) faleceram até o 90º dia comparado a 5 (6,3%) do grupo não frágil (p<0,001). Após ajuste para variáveis demográficas e clínicas, a fragilidade manteve-se no modelo como um preditor independente de mortalidade em 90 dias da admissão. A acurácia obtida pela curva ROC (AUROC) para predição de mortalidade em 90 dias foi de 0,81. Para mortalidade em 180 dias foi 0,80; para necessidade de atenção domiciliar, 0,77; e para reinternação, 0,65. Para os demais desfechos estudados, a acurácia não foi significativa. Conclusão A fragilidade basal medida pela CFS é um bom preditor de mortalidade em 90 e 180 dias e de necessidade de atenção domiciliar em idosos admitidos no SHE. Sua aplicação nesse cenário pode auxiliar na tomada de decisões clínicas.

Abstract Objective To evaluate the ability of the Clinical Frailty Scale (CFS) to predict 90-day mortality and other poor outcomes in older adults admitted at a Hospital Emergency Department (ED). Method This is a prospective cohort study including older adults admitted at ED of a Public Hospital who spent at least one night in it. The degree of baseline frailty was assessed through the CFS, and its score was the predictor studied, through the Receiver Operator Characteristics (ROC) curve analysis. We analyzed 90-day mortality as a primary outcome. The following outcomes were considered as secondary ones: mortality, functional decline, readmittance to ED, readmission and need for home care. Results 206 participants were included. Of the 127 frail older adults, 40 (31.5%) died before the 90th day compared to 5 (6.3%) in the non-frail group (p<0.001). After adjustment for demographic and clinical variables, frailty remained in the model as an independent predictor of 90-day mortality. The accuracy obtained by the ROC curve (AUROC) for predicting 90-day mortality was 0.81. For 180-day mortality, 0.80, for the need for home care, 0.77 for readmission, 0.65. For the other outcomes studied, the accuracy was not significant. Conclusion Baseline frailty measured by the CFS is a good predictor of 90 and 180-day mortality and needing for home care in older adults admitted to ED. Its application in this setting might help clinical decision-making.

Evaluation of the Biomarkers HMGB1 and IL-6 as Predictors of Mortality in Cirrhotic Patients with Acute Kidney Injury.

BACKGROUND: Acute kidney injury (AKI) affects from 20% to 50% of cirrhotic patients, and the one-month mortality rate is 60%. The main cause of AKI is bacterial infection, which worsens circulatory dysfunction through the release of HMGB1 and IL-6. OBJECTIVES: To evaluate HMGB1 and IL-6 as biomarkers of morbidity/mortality. METHODS: Prospective, observational study of 25 hospitalised cirrhotic patients with AKI. Clinical and laboratory data were collected at the time of diagnosis of AKI, including serum HMGB1 and IL-6. RESULTS: The mean age was 55 years; 70% were male. Infections accounted for 13 cases. The 30-day and three-month mortality rates were 17.4% and 30.4%, respectively. HMGB1 levels were lower in survivors than in nonsurvivors at 30 days (1174.2 pg/mL versus 3338.5 pg/mL, p = 0.035), but not at three months (1540 pg/mL versus 2352 pg/mL, p = 0.243). Serum IL-6 levels were 43.3 pg/mL versus 153.3 pg/mL (p = 0.061) at 30 days and 35.8 pg/mL versus 87.9 pg/mL (p = 0.071) at three months, respectively. The area under the ROC curve for HMGB1 was 0.842 and 0.657, and that for IL-6 was 0.803 and 0.743 for discriminating nonsurvivors at 30 days and three months, respectively. In multivariate analysis, no biomarker was independently associated with mortality. CONCLUSION: HMGB1 levels were associated with decreased survival in cirrhotics. Larger studies are needed to confirm our results.

Clinical Aspects and Prognosis Evaluation of Cirrhotic Patients Hospitalized with Acute Kidney Injury.

Background: Acute kidney injury occurs in approximately 20% of hospitalized cirrhotic patients. Mortality is estimated at 60% within a month and 65% within a year. Aims: To evaluate survival in 30 days and in 3 months of cirrhotic patients hospitalized with acute kidney injury, identifying factors associated with mortality. Methods: 52 patients with cirrhosis admitted to an academic tertiary center who presented acute kidney injury according to the International Club of Ascites criteria were evaluated. Clinical and laboratory data was collected at diagnosis between 2011 and 2015. Results: Average age was 54.6 (±10.7) years and 69.2% were male. The average MELD, MELD-Na, and Child-Pugh scores were 21.9 (±7.0), 24.5 (±6.7), and 10.1 (±2.2), respectively. Thirty patients (57.7%) were in acute kidney injury stage 1, 16 (30.8%) in stage 2, and six (11.6%) in stage 3. Mortality was 28.6% in 30 days and 44.9% in three months. In multivariate analysis, variables that were associated independently to mortality were lack of response to expansion treatment and Child-Pugh score. Mortality was 93.3% in three months among nonresponders compared to 28.6% among those who responded to volume expansion (p<0.0001). Conclusion: Acute kidney injury in cirrhosis has dire prognosis, particularly in patients with advanced cirrhosis and in nonresponders to volume expansion.

Avaliação da interleucina 3 como marcador prognóstico na sepse / Role of interleukin-3 as a prognostic marker in septic patients

RESUMO Objetivo: Avaliar a acurácia dos níveis de interleucina 3 para predizer prognóstico em pacientes sépticos. Métodos: Conduzimos uma coorte prospectiva que incluiu pacientes adultos internados em unidade de terapia intensiva, que apresentassem sepse ou choque séptico iniciados há até 48 horas. Mediram-se os níveis séricos de interleucina 3 quando da inclusão (dia 1) e nos dias 3 e 7. O desfecho primário analisado foi a mortalidade hospitalar por qualquer causa. Resultados: Foram incluídos 120 pacientes. Os níveis séricos de interleucina 3 dosados à inclusão foram significativamente mais elevados em pacientes que faleceram em comparação aos que sobreviveram à internação hospitalar (91,2pg/mL versus 36pg/mL; p = 0,024). Em modelo de sobrevivência de Cox com inclusão de idade e valores sequenciais de SOFA, os níveis de interleucina 3 mensurados na inclusão mantiveram-se independentemente associados à mortalidade hospitalar (HR 1,032; IC95% 1,010 - 1,055; p = 0,005). Em curva Característica de Operação do Receptor construída para investigação adicional da acurácia da interleucina 3 na predição do prognóstico, encontrou-se área sob a curva de 0,62 (IC95% 0,51 - 0,73; p = 0,024) para mortalidade hospitalar. Valores iniciais de interleucina 3 acima de 127,5pg/mL mostraram-se significativamente associados à mortalidade hospitalar (p = 0,019; OR = 2,97; IC95% 1,27 - 6,97; p = 0,019), entretanto com baixo desempenho (especificidade de 82%, sensibilidade de 39%, valor preditivo positivo de 53%, valor preditivo negativo de 72%, razão de verossimilhança negativa de 0,73 e razão de verossimilhança positiva de 2,16). Conclusão: Níveis elevados de interleucina 3 mostraram-se independentemente associados à mortalidade hospitalar em pacientes sépticos, entretanto com baixo desempenho clínico.

ABSTRACT Objective: To evaluate the accuracy of IL-3 to predict the outcome of septic patients. Methods: Prospective cohort study with adult patients in an intensive care unit with sepsis or septic shock diagnosed within the previous 48 hours. Circulating IL-3 levels were measured upon inclusion (day 1) and on days 3 and 7. The primary outcome was hospital mortality. Results: One hundred and twenty patients were included. Serum levels of IL-3 on day 1 were significantly higher among patients who died than among patients who survived the hospital stay (91.2pg/mL versus 36pg/mL, p = 0.024). In a Cox survival model considering the IL-3 levels at inclusion, age and sequential SOFA, IL-3 values remained independently associated with mortality (HR 1.032; 95%CI 1.010 - 1.055; p = 0.005). An receiver operating characteristic curve was built to further investigate the accuracy of IL-3, with an area under the curve of 0.62 (95%CI 0.51 - 0.73; p = 0.024) for hospital mortality. A cutoff initial IL-3 value above 127.5pg/mL was associated with hospital mortality (OR 2.97; 95%CI: 1.27 - 6.97; p = 0.0019) but with a low performance (82% for specificity, 39% for sensibility, 53% for the positive predictive value, 72% for the negative predictive value, 0.73 for the negative likelihood and 2.16 for the positive likelihood ratio). Conclusion: Higher levels of IL-3 are shown to be independently associated with hospital mortality in septic patients but with poor clinical performance.

Leptin as an obesity marker in rheumatoid arthritis.

The determination of excess of body fat mass provides a more suitable determinant of obesity in rheumatoid arthritis patients; however, body mass index (BMI) may not be accurate for the quantification of adiposity. To identify a marker of excess adiposity in women with rheumatoid arthritis (RA) using different methods for fat mass evaluation. A cross-sectional study was conducted in adult female patients with RA. Disease activity was assessed by DAS28-ESR, and obesity was determined by waist circumference (WC), BMI and dual-energy X-ray absorptiometry (DXA). The Human Bone Metabolism kit (Merck Millipore, Darmstadt, Alemanha) was used to determine the plasma levels of leptin, TNF-α, IL-6, and IL-1ß by quantification of serum proteins by technical microspheres (LUMINEX, TX, USA). Adiponectin was measured by enzyme-linked immunosorbent assay sandwich kit (R&D Systems, Minneapolis, MN, USA). Eighty-nine female patients, median age of 55.4 (± 11.6) years, and median disease duration of 16.4 (± 14.9) years were included. The frequency of obesity was 33.7% according to BMI, 89.9% with WC, and 56.1% with DXA. The median serum leptin concentration was the only marker that correlated with body fat percentage according to the three methods. This correlation was positive and not influenced by DAS28, C-reactive protein, erythrocyte sedimentation rate, or inflammatory cytokines levels (IL-6, TNF-α, IL-1ß). Analysis of ROC curves determined the cut-off point of 10.3 ng/mL of leptin as an obesity marker, with a sensitivity of 96.43% and a specificity of 23.81%. Serum leptin correlates positively with fat mass and is potentially useful in excess fat mass determination in clinical practice.

Role of interleukin-3 as a prognostic marker in septic patients. / Avaliação da interleucina 3 como marcador prognóstico na sepse.

OBJECTIVE: To evaluate the accuracy of IL-3 to predict the outcome of septic patients. METHODS: Prospective cohort study with adult patients in an intensive care unit with sepsis or septic shock diagnosed within the previous 48 hours. Circulating IL-3 levels were measured upon inclusion (day 1) and on days 3 and 7. The primary outcome was hospital mortality. RESULTS: One hundred and twenty patients were included. Serum levels of IL-3 on day 1 were significantly higher among patients who died than among patients who survived the hospital stay (91.2pg/mL versus 36pg/mL, p = 0.024). In a Cox survival model considering the IL-3 levels at inclusion, age and sequential SOFA, IL-3 values remained independently associated with mortality (HR 1.032; 95%CI 1.010 - 1.055; p = 0.005). An receiver operating characteristic curve was built to further investigate the accuracy of IL-3, with an area under the curve of 0.62 (95%CI 0.51 - 0.73; p = 0.024) for hospital mortality. A cutoff initial IL-3 value above 127.5pg/mL was associated with hospital mortality (OR 2.97; 95%CI: 1.27 - 6.97; p = 0.0019) but with a low performance (82% for specificity, 39% for sensibility, 53% for the positive predictive value, 72% for the negative predictive value, 0.73 for the negative likelihood and 2.16 for the positive likelihood ratio). CONCLUSION: Higher levels of IL-3 are shown to be independently associated with hospital mortality in septic patients but with poor clinical performance.

OBJETIVO: Avaliar a acurácia dos níveis de interleucina 3 para predizer prognóstico em pacientes sépticos. MÉTODOS: Conduzimos uma coorte prospectiva que incluiu pacientes adultos internados em unidade de terapia intensiva, que apresentassem sepse ou choque séptico iniciados há até 48 horas. Mediram-se os níveis séricos de interleucina 3 quando da inclusão (dia 1) e nos dias 3 e 7. O desfecho primário analisado foi a mortalidade hospitalar por qualquer causa. RESULTADOS: Foram incluídos 120 pacientes. Os níveis séricos de interleucina 3 dosados à inclusão foram significativamente mais elevados em pacientes que faleceram em comparação aos que sobreviveram à internação hospitalar (91,2pg/mL versus 36pg/mL; p = 0,024). Em modelo de sobrevivência de Cox com inclusão de idade e valores sequenciais de SOFA, os níveis de interleucina 3 mensurados na inclusão mantiveram-se independentemente associados à mortalidade hospitalar (HR 1,032; IC95% 1,010 - 1,055; p = 0,005). Em curva Característica de Operação do Receptor construída para investigação adicional da acurácia da interleucina 3 na predição do prognóstico, encontrou-se área sob a curva de 0,62 (IC95% 0,51 - 0,73; p = 0,024) para mortalidade hospitalar. Valores iniciais de interleucina 3 acima de 127,5pg/mL mostraram-se significativamente associados à mortalidade hospitalar (p = 0,019; OR = 2,97; IC95% 1,27 - 6,97; p = 0,019), entretanto com baixo desempenho (especificidade de 82%, sensibilidade de 39%, valor preditivo positivo de 53%, valor preditivo negativo de 72%, razão de verossimilhança negativa de 0,73 e razão de verossimilhança positiva de 2,16). CONCLUSÃO: Níveis elevados de interleucina 3 mostraram-se independentemente associados à mortalidade hospitalar em pacientes sépticos, entretanto com baixo desempenho clínico.

Omega-3 fatty acids, inflammatory status and biochemical markers of patients with systemic lupus erythematosus: a pilot study / Ácidos graxos ômega-3, estado inflamatório e marcadores bioquímicos de pacientes com lúpus eritematoso sistêmico: estudo piloto

Abstract Background: Studies have shown that omega-3 fatty acids reduce the concentrations of eicosanoids, cytokines, chemokines, C-reactive protein (CRP) and other inflammatory mediators. Objective: To investigate the effects of omega-3 fatty acids on circulating levels of inflammatory mediators and biochemical markers in women with systemic lupus erythematosus (SLE). Methods: Experimental clinical study (clinical trial: NCT02524795); 49 women with SLE (ACR1982/1997) were randomized: 22 to the omega-3 group (daily intake of 1080 mg EPA + 200 mg DHA, for 12 weeks) and 27 to the control group. The inflammatory mediators and biochemical markers at T0 and T1 in omega-3 group were compared using Wilcoxon test. U-Mann-Whitney test was used to compare variations of measured variables [ΔV = pre-treatment (T0) − post-treatment (T1) concentrations] between groups. p < 0.05 was considered significant. Results: The median (interquartile range - IQR) of age was 37 (29-48) years old, of disease duration was 7 (4-13) years, and of SLEDAI-2K was 1 (0-2). The median (IQR) of variation in CRP levels between the two groups showed a decrease in omega-3 group while there was an increase in control group (p = 0.008). The serum concentrations of IL-6 and IL-10, leptin and adiponectin did not change after a 12 week treatment. Conclusions: Supplementation with omega-3 had no impact on serum concentrations of IL-6, IL-10, leptin and adiponectin in women with SLE and low disease activity. There was a significant decrease of CRP levels as well as evidence that omega-3 may impact total and LDL-cholesterol.

Resumo Introdução: Estudos têm mostrado que os ácidos graxos ômega-3 reduzem as concentrações de eicosanoides, citocinas, quimiocinas, proteína C-reativa (PCR) e outros mediadores inflamatórios. Objetivo: Investigar os efeitos dos ácidos graxos ômega-3 sobre os níveis circulantes de mediadores inflamatórios e marcadores bioquímicos em mulheres com lúpus eritematoso sistêmico (LES). Métodos: Ensaio clínico randomizado (ensaio clínico: NCT02524795); randomizaram-se 49 mulheres com LES (ACR1982/1997): 22 para o grupo ômega-3 (dose diária de 1.080 mg de EPA + 200 mg de DHA durante 12 semanas) e 27 para o grupo controle. Os mediadores inflamatórios e marcadores bioquímicos em T0 e T1 no grupo ômega-3 foram comparados pelo teste de Wilcoxon. O teste U de Mann-Whitney foi usado para comparar variações das variáveis mensuradas [ΔV = concentrações pré-tratamento (T0) menos concentrações pós-tratamento (T1)] entre os grupos. Um p < 0,05 foi considerado significativo. Resultados: A mediana (intervalo interquartil-IIQ) da idade foi de 37 anos (29-48), a duração da doença foi de sete anos (4-13) anos e o Systemic Lupus Disease Activity Index (Sledai-2 K) foi de 1 (0-2). A mediana (IIQ) da variação nos níveis de PCR entre os dois grupos mostrou um decréscimo no grupo ômega-3, enquanto houve um aumento no grupo controle (p = 0,008). As concentrações séricas de IL-6 e IL-10, leptina e adiponectina não se alteraram após um tratamento de 12 semanas. Conclusões: A suplementação de ômega-3 não teve impacto sobre as concentrações séricas de IL-6, IL-10, leptina e adiponectina em mulheres com LES e baixa atividade da doença. Houve uma diminuição significativa nos níveis de PCR, bem como evidências de que o ômega-3 pode impactar sobre o colesterol total e LDL.

Which is the best cutoff of body mass index to identify obesity in female patients with rheumatoid arthritis? A study using dual energy X-ray absorptiometry body composition / Qual o melhor ponto de corte de índice de massa corporal para diagnosticar a obesidade em mulheres com artrite reumatoide? Um estudo que usa a composição corporal pela absorciometria com raios X de dupla energia

ABSTRACT Introduction: Standard anthropometric measures used to diagnose obesity in the general population may not have the same performance in patients with rheumatoid arthritis. Objective: To determine cutoff points for body mass index (BMI) and waist circumference (WC) for detecting obesity in women with rheumatoid arthritis (RA) by comparing these standard anthropometric measures to a dual-energy X-ray absorptiometry (DXA)-based obesity criterion. Patients and method: Adult female patients with more than six months of diagnosis of RA underwent clinical evaluation, with anthropometric measures and body composition with DXA. Results: Eighty two patients were included, mean age 55 ± 10.7 years. The diagnosis of obesity in the sample was about 31.7% by BMI, 86.6% by WC and 59.8% by DXA. Considering DXA as golden standard, cutoff points were identified for anthropometric measures to better approximate DXA estimates of percent body fat: for BMI value ≥ 25 kg/m2 was the best for definition of obesity in female patients with RA, with sensitivity of 80% and specificity of 60%. For WC, with 80% of sensitivity and 35% of specificity, the best value to detect obesity was 86 cm. Conclusion: A large percentage of patients were obese. The traditional cutoff points used for obesity were not suitable for our sample. For this female population with established RA, BMI cutoff point of 25 kg/m2 and WC cutoff point of 86 cm were the most appropriate to detect obesity.

RESUMO Introdução: Medidas antropométricas universalmente usadas para diagnosticar obesidade na população geral podem não apresentar a mesma performance em pacientes com artrite reumatoide. Objetivos: Determinar pontos de corte do índice de massa corporal (IMC) e da circunferência de cintura (CC) para detecção de obesidade em mulheres com artrite reumatoide (AR) por meio da comparação dessas medidas antropométricas habituais com os índices de adiposidade obtidos pela densitometria óssea por dupla emissão de raios X (DXA). Pacientes e método: Mulheres adultas com mais de seis meses de diagnóstico de AR foram submetidas a avaliação clínica com medidas antropométricas e à DXA com exame da composição corporal. Resultados: Foram incluídas 82 pacientes, média de 55± 10,7 anos. O diagnóstico de obesidade na amostra foi de 31,7% pelo IMC, 86,6% pela circunferência de cintura e 59,8% pela DXA. Considerando a DXA o padrão-ouro, o valor de IMC acima de 25 kg/m2 foi o mais adequado para definição de obesidade nas pacientes com AR, apresentou sensibilidade de 80% e especificidade de 60%. Da mesma forma, para a CC, com 80% de sensibilidade e de 35% de especificidade, o valor encontrado foi de 86 cm para se detectar a obesidade. Conclusão: Foi elevado o porcentual de pacientes obesas. Os pontos de corte tradicionalmente usados para obesidade não foram adequados para nossa amostra. Para essa população de pacientes femininas com diagnóstico de AR, o ponto de corte de 25 kg/m2 para IMC e de 86 cm para CC foi o mais adequado para definir obesidade.

Which is the best cutoff of body mass index to identify obesity in female patients with rheumatoid arthritis? A study using dual energy X-ray absorptiometry body composition.

INTRODUCTION: Standard anthropometric measures used to diagnose obesity in the general population may not have the same performance in patients with rheumatoid arthritis. OBJECTIVE: To determine cutoff points for body mass index (BMI) and waist circumference (WC) for detecting obesity in women with rheumatoid arthritis (RA) by comparing these standard anthropometric measures to a dual-energy X-ray absorptiometry (DXA)-based obesity criterion. PATIENTS AND METHOD: Adult female patients with more than six months of diagnosis of RA underwent clinical evaluation, with anthropometric measures and body composition with DXA. RESULTS: Eighty two patients were included, mean age 55±10.7 years. The diagnosis of obesity in the sample was about 31.7% by BMI, 86.6% by WC and 59.8% by DXA. Considering DXA as golden standard, cutoff points were identified for anthropometric measures to better approximate DXA estimates of percent body fat: for BMI value≥25kg/m2 was the best for definition of obesity in female patients with RA, with sensitivity of 80% and specificity of 60%. For WC, with 80% of sensitivity and 35% of specificity, the best value to detect obesity was 86cm. CONCLUSION: A large percentage of patients were obese. The traditional cutoff points used for obesity were not suitable for our sample. For this female population with established RA, BMI cutoff point of 25kg/m2 and WC cutoff point of 86cm were the most appropriate to detect obesity.

Which is the best cutoff of body mass index to identify obesity in female patients with rheumatoid arthritis? A study using dual energy X-ray absorptiometry body composition. / Qual o melhor ponto de corte de índice de massa corporal para diagnosticar a obesidade em mulheres com artrite reumatoide? Um estudo que usa a composição corporal pela absorciometria com raios X de dupla energia.

INTRODUCTION: Standard anthropometric measures used to diagnose obesity in the general population may not have the same performance in patients with rheumatoid arthritis. OBJECTIVE: To determine cutoff points for body mass index (BMI) and waist circumference (WC) for detecting obesity in women with rheumatoid arthritis (RA) by comparing these standard anthropometric measures to a dual-energy x-ray absorptiometry (DXA)-based obesity criterion. PATIENTS AND METHOD: Adult female patients with more than six months of diagnosis of RA underwent clinical evaluation, with anthropometric measures and body composition with DXA. RESULTS: Eighty two patients were included, mean age 55±10.7 years. The diagnosis of obesity in the sample was about 31.7% by BMI, 86.6% by WC and 59.8% by DXA. Considering DXA as golden standard, Cutoff points were identified for anthropometric measures to better approximate DXA estimates of percent body fat: for BMI value ≥ 25kg/m2 was the best for definition of obesity in female patients with RA, with sensitivity of 80% and specificity of 60%. For WC, with 80% of sensitivity and 35% of specificity, the best value to detect obesity was 86cm. CONCLUSION: A large percentage of patients were obese. The traditional cutoff points used for obesity were not suitable for our sample. For this female population with established RA, BMI cutoff point of 25kg/m2 and WC cutoff point of 86cm were the most appropriate to detect obesity.

Mast cells are crucial in the resistance against Toxoplasma gondii oral infection.

During oral infection, mucosal immunity assumes a predominant role. Here, we addressed the role of mast cells (MCs), which are mainly located in mucosa during oral infection with Toxoplasma gondii, using MC-deficient (W/W(v) ) mice. We show that in the absence of MCs the resistance of W/W(v) mice to oral infection was considerably reduced. W/W(v) mice uniformly succumbed within 15 days of infection after administration of cysts of the ME49 strain of T. gondii. The rapid lethality of T. gondii in W/W(v) mice correlated with a delayed Th1-cell response, since IFN-γ and IL-12 levels peaked in the later phase of the infection. In vitro, BM-derived MCs were able to recognize parasite lysate in a MyD88-dependent way, reaffirming the role of this TLR adapter in immune responses to T. gondii. The importance of MCs in vivo was confirmed when W/W(v) mice reconstituted with BM-derived MCs from control mice retrieved an early strong Th1-cell response and specially a significant IL-12 production. In conclusion, MCs play an important role for the development of a protective immune response during oral infection with T. gondii.

Matrix metalloproteinase 2 activity decreases in human periodontal ligament fibroblast cultures submitted to simulated orthodontic force.

Orthodontic force compresses the periodontal ligament promoting the expression of pro-inflammatory mediators and matrix metalloproteinases responsible for tooth movement. The extent in time while periodontal cells are being treated and the increment in the amount of mechanical stress caused by the orthodontic force is thought to regulate the levels of metalloproteinases in the periodontal tissue. To study the possible regulation in the activity of metalloproteinases 2, 3, 7, 9, and 10 by simulated orthodontic force, human periodontal ligament fibroblast cultures were centrifuged (141 × g) for 30, 60, 90, and 120 min, simulating the orthodontic force. Cell viability, protein quantification, and activity of metalloproteinases by zymography were evaluated at 24, 48, and 72 h after centrifugation in both cell lysates and growth medium. The activity of the 72-kDa matrix metalloproteinase 2 was decreased at 24 h regardless of the duration of centrifugation and at 48 h in cells centrifuged for 30 min only. Decrease in the amount of total protein in lysates was seen at 48 and 72 h with no change in cell viability. The data seem to indicate that the amount of mechanical stress regulates the levels of secreted matrix metalloproteinase 2. In addition, the centrifugation as a model for simulated orthodontic force may be used as a simple and reliable method to study the role played by matrix metalloproteinases in periodontal ligament when submitted to mechanical force as occurring during tooth movement.