The effect of antimalarials on the safety and persistence of treatment with biologic agents or Janus kinase inhibitors in rheumatoid arthritis.

OBJECTIVES: To test the association of use of antimalarials with the overall safety of treatment in RA patients receiving one or multiple courses of biologic (b)DMARDs or a Janus kinase inhibitor (JAKi). METHODS: BiobadaBrasil is a multicentric registry-based cohort study of Brazilian patients with rheumatic diseases starting their first bDMARD or JAKi. The present analysis includes RA patients recruited from January 2009 to October 2019, followed up over one or multiple (up to six) courses of treatment (latest date, 19 November 2019). The primary outcome was the incidence of serious adverse events (SAEs). Total and system-specific adverse events (AEs) and treatment interruption served as secondary outcomes. Negative binomial regression with generalized estimating equations (to estimate multivariate incidence rate ratios, mIRR) and frailty Cox proportional hazards models were used for statistical analyses. RESULTS: The number of patients enrolled was 1316 (2335 treatment courses, 6711 patient-years [PY]; 1254.5 PY on antimalarials). The overall incidence of SAEs was 9.2/100 PY. Antimalarials were associated with reduced risk of SAEs (mIRR: 0.49; 95% CI: 0.36, 0.68; P < 0.001), total AEs (0.68; 95% CI: 0.56, 0.81; P < 0.001), serious infections (0.53; 95% CI: 0.34, 0.84; P = 0.007) and total hepatic AEs (0.21; 95% CI: 0.05, 0.85; P = 0.028). Antimalarials were also related to better survival of treatment course (P = 0.003). There was no significant increase in the risk of cardiovascular AEs. CONCLUSION: Among RA patients on treatment with bDMARDs or JAKi, concomitant use of antimalarials was associated with reduced the incidence of serious and total AEs and with longer treatment course survival.

Evaluation of Screws Positioning in Latarjet Surgery: Is There a Correlation between Parallelism to Glenoid and Radiographic Complications?

Objective To evaluate whether the parallelism of screws with glenoid in Latarjet surgery interferes in the positioning of the graft and to verify the reproducibility of a method of measuring screws positioning. Methods Retrospective, multicenter study, of patients with anterior shoulder instability submitted to modified Latarjet surgery and at least one year of postoperative follow-up. Two radiologists analyzed the postoperative tomographic images, acquired in a database, to evaluate the positioning of screws and radiographic complications. Results We evaluated 34 patients, aged between 21 and 60 years, one of them with bilateral shoulder involvement, totaling 35 shoulders evaluated. The tomographic evaluation of the inclination angles of the screws showed no difference between the observers. There was intra- and interobserver agreement to evaluate the following surgical parameters: graft position, presence or not of radiographic complications. Conclusion The technique described for measuring the parallelism of screws in Latarjet surgery presented a very good and excellent intra-observer agreement, respectively. Screw parallelism with glenoid is recommended; however, it is not a mandatory and unique condition to avoid radiographic complications.

Attributable mortality due to nosocomial sepsis in Brazilian hospitals: a case-control study.

BACKGROUND: Nosocomial sepsis is a major healthcare issue, but there are few data on estimates of its attributable mortality. We aimed to estimate attributable mortality fraction (AF) due to nosocomial sepsis. METHODS: Matched 1:1 case-control study in 37 hospitals in Brazil. Hospitalized patients in participating hospitals were included. Cases were hospital non-survivors and controls were hospital survivors, which were matched by admission type and date of discharge. Exposure was defined as occurrence of nosocomial sepsis, defined as antibiotic prescription plus presence of organ dysfunction attributed to sepsis without an alternative reason for organ failure; alternative definitions were explored. Main outcome measurement was nosocomial sepsis-attributable fractions, estimated using inversed-weight probabilities methods using generalized mixed model considering time-dependency of sepsis occurrence. RESULTS: 3588 patients from 37 hospitals were included. Mean age was 63 years and 48.8% were female at birth. 470 sepsis episodes occurred in 388 patients (311 in cases and 77 in control group), with pneumonia being the most common source of infection (44.3%). Average AF for sepsis mortality was 0.076 (95% CI 0.068-0.084) for medical admissions; 0.043 (95% CI 0.032-0.055) for elective surgical admissions; and 0.036 (95% CI 0.017-0.055) for emergency surgeries. In a time-dependent analysis, AF for sepsis rose linearly for medical admissions, reaching close to 0.12 on day 28; AF plateaued earlier for other admission types (0.04 for elective surgery and 0.07 for urgent surgery). Alternative sepsis definitions yield different estimates. CONCLUSION: The impact of nosocomial sepsis on outcome is more pronounced in medical admissions and tends to increase over time. The results, however, are sensitive to sepsis definitions.

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.

Evaluation of Screws Positioning in Latarjet Surgery: Is There a Correlation between Parallelism to Glenoid and Radiographic Complications? / Avaliação do posicionamento dos parafusos na cirurgia de Latarjet: Existe correlação entre paralelismo à glenoide e complicações radiográficas?

Abstract Objective To evaluate whether the parallelism of screws with glenoid in Latarjet surgery interferes in the positioning of the graft and to verify the reproducibility of a method of measuring screws positioning. Methods Retrospective, multicenter study, of patients with anterior shoulder instability submitted to modified Latarjet surgery and at least one year of postoperative follow-up. Two radiologists analyzed the postoperative tomographic images, acquired in a database, to evaluate the positioning of screws and radiographic complications. Results We evaluated 34 patients, aged between 21 and 60 years, one of them with bilateral shoulder involvement, totaling 35 shoulders evaluated. The tomographic evaluation of the inclination angles of the screws showed no difference between the observers. There was intra- and interobserver agreement to evaluate the following surgical parameters: graft position, presence or not of radiographic complications. Conclusion The technique described for measuring the parallelism of screws in Latarjet surgery presented a very good and excellent intra-observer agreement, respectively. Screw parallelism with glenoid is recommended; however, it is not a mandatory and unique condition to avoid radiographic complications.

Resumo Objetivo Avaliar se o paralelismo dos parafusos com a glenoide na cirurgia de Latarjet interfere no posicionamento do enxerto e verificar a reprodutibilidade de um método de mensuração da posição dos parafusos. Métodos Estudo retrospectivo, multicêntrico, de pacientes com instabilidade anterior do ombro submetidos à cirurgia de Latarjet modificada e no mínimo 1 ano de seguimento pós-operatório. Dois médicos radiologistas analisaram as imagens tomográficas pós-operatórias, adquiridas em um banco de dados, para avaliação do posicionamento dos parafusos e das complicações radiográficas. Resultados Foram avaliados 34 pacientes, com idades entre 21 e 60 anos, sendo que um deles tinha acometimento bilateral dos ombros, totalizando 35 ombros avaliados. A avaliação tomográfica dos ângulos de inclinação dos parafusos não apresentou diferença entre os observadores. Houve concordância intra e interobservador para avaliação dos seguintes parâmetros cirúrgicos: posição do enxerto, presença ou não de complicações radiográficas. Conclusão A técnica descrita para mensuração do paralelismo dos parafusos na cirurgia de Latarjet apresentou uma concordância intra e inter observador muito boa e excelente, respectivamente. O paralelismo do parafuso com a glenoide é recomendado; no entanto, não é condição obrigatória e única para se evitar as complicações radiográficas.

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

Abstract 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.

Immunostimulant Activity of Bacteria Isolated from Extreme Environments in Baja California Sur, Mexico: A Bioprospecting Approach.

Excessive use of antibiotics has led to an increase of pathogenic bacteria with multiple antibiotic resistance. Hypersaline and hyperthermal environments promote the development of several microorganisms that can potentially act as immunostimulants. Thus, the aim of this study was bioprospecting marine bacteria from these environments using mouse leukocytes as a cell model for assess immunostimulatory activity. Samples were taken from two evaporation ponds with 4 and 8% salinity (p/v) in a marine solar saltern (MSS) at Laguna Ojo de Liebre, Guerrero Negro and a shallow hydrothermal vent (SHV), Bahía Concepción under a mangrove forest both off Baja California Sur, México. From total number of isolates (N = 340), 267 were obtained from the MSS and 73 from the SHV. The 10 isolates that induced nitric oxide (NO) production in mouse splenocytes were identified using the 16S rRNA gene, of which Halomonas elongata, Halomonas sp., Pseudoalteromonas ruthenica, Bacillus subtilis and three Bacillus strains were isolated from the MSS ponds at 8% salinity and three Marinobacter lutaoensis strains from the SHV. Most of the selected bacteria were not cytotoxic for mouse splenocytes and enhanced phagocytic respiratory burst and antioxidant enzyme activities compared to the control immunostimulant (lipopolysaccharide from Escherichia coli). Selected bacteria from 8% salinity ponds in the MSS in Guerrero Negro had immunostimulant activity in vitro in mouse splenocytes. In conclusion, Bacillus subtilis SA4 220, Bacillus sp. SA4 62A, P. ruthenica SA4 40 as well as Halomonas sp. SA4 207 and Halomonas elongata SA8 44 increased several immunological parameters. Further research is needed to evaluate their potential application in preclinical models to fight against infectious diseases. Supplementary Information: The online version contains supplementary material available at 10.1007/s12088-022-01002-3.

Safety of the Methotrexate-leflunomide Combination in Rheumatoid Arthritis: Results of a Multicentric, Registry-based, Cohort Study (BiobadaBrasil).

OBJECTIVE: To evaluate the safety of the methotrexate (MTX)-leflunomide (LEF) combination in rheumatoid arthritis (RA), comparing it with other therapeutic schemes involving conventional synthetic (cs-) and biologic (b-) disease-modifying antirheumatic drugs (DMARDs) or Janus kinase inhibitors (JAKi). METHODS: Patients with RA starting a treatment course with a csDMARD (without previous use of bDMARD or JAKi) or their first bDMARD/JAKi were followed up in a registry-based, multicentric cohort study in Brazil (BiobadaBrasil). The primary outcome was the incidence of serious adverse events (SAEs); secondary outcomes included serious infections. Multivariate Cox proportional hazards models and propensity score matching analysis (PSMA) were used for statistical comparisons. RESULTS: In total, 1671 patients (5349 patient-years [PY]) were enrolled; 452 patients (1537 PY) received MTX + LEF. The overall incidence of SAEs was 5.6 per 100 PY. The hazard of SAEs for MTX + LEF was not higher than for MTX or LEF (adjusted HR [aHR] 1.00, 95% CI 0.76-1.31, P = 0.98). MTX + LEF presented a lower hazard of SAEs (aHR 0.56, 95% CI 0.36-0.88, P = 0.01) and infectious SAEs (aHR 0.48, 95% CI 0.25-0.94, P = 0.03) than bDMARDs/JAKi with MTX or LEF. MTX + LEF presented lower hazard of SAEs than MTX + sulfasalazine (SSZ; aHR 0.33, 95% CI 0.16-0.65, P = 0.002). Analysis using PSMA confirmed the results obtained with traditional multivariate Cox analysis. CONCLUSION: In our study, MTX + LEF presented a relatively good overall safety profile in comparison to MTX + SSZ and schemes involving advanced therapies in RA.

High Levels of Polypharmacy in Rheumatoid Arthritis-A Challenge Not Covered by Current Management Recommendations: Data From a Large Real-Life Study.

BACKGROUND: Rheumatoid arthritis (RA) is associated with high frequency of comorbidities and increased risk of polypharmacy. Although there is a great potential for complications, there is a gap in literature on polypharmacy in patients with rheumatic arthritis. OBJECTIVE: To evaluate the prevalence and factors associated with polypharmacy in a population in a real-life setting. METHODS: A cross-sectional multicenter study was conducted in Brazil. Patients underwent clinical evaluation and medical records analysis. Polypharmacy was considered as a dependent variable. To test independent variables, we used Poisson regression. RESULTS: We evaluated 792 patients (89% female, median age 56.6 years). Median duration of disease was 12.7 years, 78.73% had a positive rheumatoid factor. The median of disease activity score-28 was 3.5 (disease with mild activity), median of the clinical disease activity index score was 9, and median of health assessment questionnaire-disability index was 0.875; 47% used corticosteroids, 9.1% used nonsteroidal anti-inflammatory drugs, 90.9% used synthetic disease-modifying antirheumatic drugs, 35.7% used biologic disease-modifying antirheumatic drugs (DMARDs). In total, 537 (67.9%) patients used 5 or more drugs. Polypharmacy showed a relationship with a number of comorbidities and use of specific drugs (corticosteroids, methotrexate, and biological DMARDs). CONCLUSION: We found a high prevalence of polypharmacy (67.9%) in RA. Solutions to management this problem should be stimulated.

Removal of middle molecules with medium cutoff dialyzer in patients on short frequent hemodialysis.

INTRODUCTION: Medium cutoff (MCO) membranes for hemodialysis (HD) remove more effectively large middle molecules than high-flux (HF) membranes. In patients on in-center short frequent HD regimen (5 sessions per week, 2 hours and 30 minutes per session) the effect of MCO on middle weight uremic toxins has not been elucidated. METHODS: This retrospective study included 15 patients previously performing short frequent HD with HF dialyzer (HF-HD), that were switched to short frequent HD with MCO dialyzer (MCO-HD) for 2 months, and returned to HF-HD. The primary endpoint was the predialysis concentration of α1-acid glycoprotein during the different study phases. Secondary endpoints were predialysis concentration of other middle molecules, albumin, and assessment of the quality of life using the 36-item short-form health survey (SF-36). FINDINGS: During MCO-HD phase there was a reduction in mean ± SD α1-acid glycoprotein concentration (98.71 ± 25.2 vs. 88.6 ± 24.6 mg/dL, P = 0.107), followed by an increment 2 months after returning to HF-HD (89.18 ± 26.12 vs. 97.33 ± 31.29 mg/dL, P = 0.002); however, only the second variation was statistically significant. MCO-HD provided lower median predialysis concentration of prolactin (16 [10.2-25.6] vs. 14.1 [11.7-34.8] ng/mL, P = 0.036). Single-pool Kt/V, standard Kt/V, predialysis ß2-microglobulin, myoglobin, and SF-36 questionnaire remained stable during the first two phases (pre-MCO and MCO). ß2-Microglobulin increased in the post-MCO phase (20.02 ± 8.14 vs. 21.27 ± 7.64 µg/mL, P = 0.000). Mean predialysis concentration of albumin reduced significantly from pre-MCO vs. MCO phases (39.9 ± 3.7 vs. 38.3 ± 3.3 g/L, P = 0.020) and rebounded significantly from MCO vs. post-MCO phases (38.7 ± 3.1 vs. 41.3 ± 3.0 g/L, P = 0.007). DISCUSSION: In this retrospective analysis, short frequent MCO-HD promotes a reduction in prolactin, a middle weight uremic toxin, and trends toward a reduction in α1-acid glycoprotein. No patients developed hypoalbuminemia. These findings are encouraging and deserve investigation in prospective studies.

A rhamnose-binding lectin from Rhodnius prolixus and the impact of its silencing on gut bacterial microbiota and Trypanosoma cruzi.

Lectins are ubiquitous proteins involved in the immune defenses of different organisms and mainly responsible for non-self-recognition and agglutination reactions. This work describes molecular and biological characterization of a rhamnose-binding lectin (RBL) from Rhodnius prolixus, which possesses a 21 amino acid signal peptide and a mature protein of 34.6 kDa. The in-silico analysis of the primary and secondary structures of RpLec revealed a lectin domain fully conserved among previous insects studied. The three-dimensional homology model of RpLec was similar to other RBL-lectins. Docking predictions with the monosaccharides showed rhamnose and galactose-binding sites comparable to Latrophilin-1 and N-Acetylgalactosamine-binding in a different site. The effects of RpLec gene silencing on levels of infecting Trypanosoma cruzi Dm 28c and intestinal bacterial populations in the R. prolixus midgut were studied by injecting RpLec dsRNA into the R. prolixus hemocoel. Whereas T. cruzi numbers remained unchanged compared with the controls, numbers of bacteria increased significantly. The silencing also induced the up regulation of the R. prolixus defC (defensin) expression gene. These results with RpLec reveal the potential importance of this little studied molecule in the insect vector immune response and homeostasis of the gut bacterial microbiota.

Guidelines To Predict Binding Poses of Antibody-Integrin Complexes.

Integrins are cell adhesion receptors that transmit bidirectional signals across the plasma membrane. They are noncovalently linked heterodimeric molecules consisting of two subunits and act as biomarkers in several pathologies. Thus, according to the increase of therapeutic antibody production, some efforts have been applied to produce anti-integrin antibodies. Here, we purposed to evaluate methods of generation and identification of the binding pose of integrin-antibody complexes, through protein-protein docking and molecular dynamics simulations, and propose a strategy to assure the confidence of the final model and avoid false-positive poses. The results show that ClusPro and GRAMM-X were the best programs to generate the native pose of integrin-antibody complexes. Furthermore, we were able to recover and to ensure that the selected pose is the native one by using a simple rule. All complexes from ClusPro in which the first model had the lowest energy, at least 5% more negative than the second one, were correctly predicted. Therefore, our methodology seems to be efficient to avoid misranking of wrong poses for integrin-antibody complexes. In cases where the rule is inconclusive, we proposed the use of heated molecular dynamics to identify the native pose characterized by RMSDi <0.5 nm. We believe that the set of methods presented here helps in the rational design of anti-integrin antibodies, giving some insights on the development of new biopharmaceuticals.

Resolving the taxonomic puzzle of Boana cinerascens (Spix, 1824), with resurrection of Hyla granosa gracilis Melin, 1941 (Anura: Hylidae).

Expeditions to unexplored or little explored places are important for discovering new species and also for collecting new samples (including specimens and tissues for DNA sequencing ) that may help resolve a plethora of taxonomic problems. In the 19th century, several naturalists explored a number of localities in Amazonia, describing species for which type material was deposited, mostly, in European museums of natural history. Some of these types were lost or destroyed in World War II and recent expeditions have focused on sampling new material from the type localities. material from Boana cinerascens, which allowed us to infer phylogenetic relationships of the Boana punctata group (i.e., green Boana), based on DNA sequence data, and to revaluate the status of B. cinerascens and its synonyms. We designate, redescribe and illustrate a neotype for B. cinerascens, which was described by Spix in 1824, from the Municipality of Tefé, State of Amazonas, Brazil. We revalidate, redescribe, and illustrate Hyla granosa gracilis Melin, 1941(= Boana gracilis). Corroborating previous studies, the green Boana were not recovered as a monophyletic group. Boana cinerascens is sister of B. gracilis plus a clade containing B. atlantica + B. punctata (both species not recovered as monophyletic).

Incidence of Infectious Adverse Events in Patients With Rheumatoid Arthritis and Spondyloarthritis on Biologic Drugs-Data From the Brazilian Registry for Biologics Monitoring.

BACKGROUND: The safety profile of biologic drugs might present substantial regional differences. Since 2009, the Brazilian Society of Rheumatology has maintained BIOBADABRASIL (Brazilian Registry for Biologic Drugs), a registry for monitoring of biologic therapies in rheumatic diseases. OBJECTIVES: The aim of this study was to verify the incidence rate (IR) of serious infections in rheumatoid arthritis (RA) and spondyloarthritis (SpA) patients on biologic drugs. METHODS: BIOBADABRASIL prospectively included patients with rheumatic diseases who started the first biologic drug or a synthetic disease-modifying antirheumatic drug as a parallel control group. This study focuses on serious infectious adverse events (SIAEs) in RA and SpA patients on biologic drugs compared with controls, from January 2009 to June 2015. Time of exposure was set from initiation of the drug to the date of last administration or censorship. Serious infectious adverse events IR was calculated per 1000 patient/years with 95% confidence interval (CI). RESULTS: A total of 1698 patients (RA, 1121; SpA, 577) were included, 7119 patient/years. Serious infectious adverse events were more common among patients on tumor necrosis factor inhibitors (TNFi's) than controls (adjusted IR ratio, 2.96 [95% CI, 2.01-4.36]; p < 0.001). Subsequent TNFi was associated with a higher SIAEs incidence when compared with first TNFI (adjusted IR ratio, 1.55 [95% CI, 1.15-2.08]; p = 0.004). Serious infectious adverse events were associated with age and corticosteroids intake. Serious infectious adverse events were more frequent in the respiratory tract in all subgroups. CONCLUSIONS: In BIOBADABRASIL, biologic drugs, especially the subsequent TNFi, were associated with a higher risk of serious infections compared with synthetic DMARDs. Corticosteroid intake and age represented risk factors for SIAEs. Constant monitoring is required to follow the safety profile of drugs in the clinical setting of rheumatic conditions in Brazil.

Epidermal growth factor vs platelet-rich plasma: Activity against chronic wound microbiota.

The objective was to evaluate Staphylococcus aureus and Pseudomonas aeruginosa colonisation of wounds treated with recombinant epidermal growth factor (EGF) and platelet-rich plasma (PRP); to analyse the susceptibility profiles of S. aureus and P. aeruginosa isolates from wounds treated with EGF and PRP; and to describe the presence of infection in EGF-treated and PRP-treated wounds. Experimental study was performed using clinical specimens collected with swabs. Patients were treated with PRP and EGF in the outpatient clinic of a university hospital. Forty-three isolates were obtained from 31 patients, 41.9% (13/31) of whom had been treated with EGF and 58.0% (18/31) with PRP. Ten of the 43 isolates were identified as S. aureus, 60.0% (6/10) of which were isolated from PRP-treated wounds. Among the 33 P. aeruginosa isolates, 66.6% (22/33) were isolated from PRP-treated wounds. Regarding antimicrobial susceptibility, only one strain isolated from an EGF-treated wound was identified as methicillin-resistant S. aureus (MRSA). Among the P. aeruginosa isolates, one obtained from a patient treated with EGF was multidrug-resistant. Patients treated with EGF had no infections during the follow-up period, and there was a significant difference between the 1st and 12th week in wound infection improvement in patients treated with PRP (P = .0078).

The Long Pentraxin 3 Contributes to Joint Inflammation in Gout by Facilitating the Phagocytosis of Monosodium Urate Crystals.

The purpose of this study was to investigate the role of pentraxin 3 (PTX3), a pivotal component of the innate immune system, in gout. Levels of PTX3 and IL-1ß in human samples were evaluated by ELISA. Development of murine gout was evaluated through the levels of cytokines (PTX3, CXCL1, and IL-1ß) and neutrophil recruitment into the joint cavity. Phagocytosis of monosodium urate (MSU) crystals and caspase-1 activation were determined by flow cytometer. Acute gout patients showed elevated concentration of PTX3 in plasma and synovial fluid as compared with healthy and osteoarthritic subjects. Moreover, there was a positive correlation between intra-articular PTX3 and IL-1ß levels. PTX3 was induced in the periarticular tissue of mice postinjection of MSU crystals. Importantly, Ptx3-deficient mice showed reduced inflammation in response to MSU crystal injection compared with wild-type mice, including reduction of neutrophil recruitment into the joint cavity and IL-1ß and CXCL1 production. Interestingly, addition of PTX3 in vitro enhanced MSU crystal phagocytosis by monocytes and resulted in higher production of IL-1ß by macrophages. This contribution of PTX3 to the phagocytosis of MSU crystals and consequent production of IL-1ß occurred through a mechanism mainly dependent on FcγRIII. Thus, our results suggest that PTX3 acts as a humoral pattern recognition molecule in gout facilitating MSU crystal phagocytosis and contributing to the pathogenesis of gouty arthritis.

[Prevalence and determinants of the increased carotid intima-media thickness in a population of 1203 black African hypertensive]. / Prévalence et facteurs déterminants de l'épaisseur intima-media carotidienne élevée dans une population de 1203 hypertendus noirs africains.

OBJECTIVES: To evaluate the prevalence and determinants of increased carotid intima-media thickness (IMT) in a population of black hypertensive patients and it influence of on the assessment of their overall cardiovascular risk. PATIENTS AND METHODS: This was a 16-month, cross-sectional study conducted in the outpatient unit of the cardiology department of the Campus teaching hospital of Lome, and included 1203 hypertensive patients, both sexes, aged 35 years and more. Each patient benefited from a carotid IMT measure. Carotid IMT was increased if it was>0.9mm and the plaque was defined as a carotid IMT>1.2mm. RESULTS: The mean age of our patients was 53.3±10.4 years with a sex ratio of 1.6 in favor of women. The duration of hypertension was less than 5 years in 56.7% and hypertension was grade 1 in 47.7% of cases. The mean carotid IMT was 0.89mm±0.20. The prevalence of the increased carotid IMT was 45.8% and that of an atheroma plaque was 15.8%. Carotid IMT was correlated with age (P˂0.0001), duration of arterial hypertension (P=0.01), history of stroke (P˂0.0001), and presence of left ventricular hypertrophy to cardiac ultrasound (P=0.01). The overall cardiovascular risk was modified after taking into account the carotid IMT. An increase in cardiovascular risk was observed in 30.5% of hypertensive patients. CONCLUSION: Increased carotid intima-media thickness is frequent in Togolese hypertension. The determining factors are age, duration of arterial hypertension, left ventricular hypertrophy and stroke. The systematic measurement of the carotid intima-media thickness would better evaluate the overall cardiovascular risk for our patients.