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OBJECTIVE: To describe obstetric outcomes based on COVID-19 vaccination status, in women with rheumatic and musculoskeletal diseases (RMDs) who developed COVID-19 during pregnancy. METHODS: Data regarding pregnant women entered into the COVID-19 Global Rheumatology Alliance registry from 24 March 2020-25 February 2022 were analysed. Obstetric outcomes were stratified by number of COVID-19 vaccine doses received prior to COVID-19 infection in pregnancy. Descriptive differences between groups were tested using the chi-squared or Fisher's exact test. RESULTS: There were 73 pregnancies in 73 women with RMD and COVID-19. Overall, 24.7% (18) of pregnancies were ongoing, while of the 55 completed pregnancies, 90.9% (50) of pregnancies resulted in livebirths. At the time of COVID-19 diagnosis, 60.3% (n = 44) of women were unvaccinated, 4.1% (n = 3) had received one vaccine dose while 35.6% (n = 26) had two or more doses. Although 83.6% (n = 61) of women required no treatment for COVID-19, 20.5% (n = 15) required hospital admission. COVID-19 resulted in delivery in 6.8% (n = 3) of unvaccinated women and 3.8% (n = 1) of fully vaccinated women. There was a greater number of preterm births (PTB) in unvaccinated women compared with fully vaccinated 29.5% (n = 13) vs 18.2% (n = 2). CONCLUSIONS: In this descriptive study, unvaccinated pregnant women with RMD and COVID-19 had a greater number of PTB compared with those fully vaccinated against COVID-19. Additionally, the need for COVID-19 pharmacological treatment was uncommon in pregnant women with RMD regardless of vaccination status. These results support active promotion of COVID-19 vaccination in women with RMD who are pregnant or planning a pregnancy.
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COVID-19 , Nascimento Prematuro , Doenças Reumáticas , Gravidez , Recém-Nascido , Feminino , Humanos , Vacinas contra COVID-19 , COVID-19/epidemiologia , COVID-19/prevenção & controle , Teste para COVID-19 , Doenças Reumáticas/tratamento farmacológico , VacinaçãoRESUMO
OBJECTIVE: MTX remains the cornerstone for therapy for RA, yet research shows that non-adherence is significant and correlates with response to therapy. This study aimed to halve self-reported non-adherence to MTX at the Kellgren Centre for Rheumatology. METHODS: An anonymous self-report adherence questionnaire was developed and data collected for 3 months prior to the introduction of interventions, and then regularly for the subsequent 2.5 years. A series of interventions were implemented, including motivational interviewing training, consistent information about MTX and development of a summary bookmark. Information on clinic times was collected for consultations with and without motivational interviewing. Surveys were conducted to ascertain consistency of messages about MTX. A biochemical assay was used to test MTX serum levels in patients at two time points: before and 2.8 years following introduction of the changes. Remission rates at 6 and 12 months post-MTX initiation were retrieved from patient notes and cost savings estimated by comparing actual numbers of new biologic starters compared with expected numbers based on the numbers of consultants employed at the two time points. RESULTS: Between June and August 2016, self-reported non-adherence to MTX was 24.7%. Following introduction of the interventions, self-reported non-adherence rates reduced to an average of 7.4% between April 2018 and August 2019. Clinic times were not significantly increased when motivational interviewing was employed. Consistency of messages by staff across three key areas (benefits of MTX, alcohol guidance and importance of adherence) improved from 64% in September 2016 to 94% in January 2018. Biochemical non-adherence reduced from 56% (September 2016) to 17% (June 2019), whilst remission rates 6 months post-initiation of MTX improved from 13% in 2014/15 to 37% in 2017/18, resulting is estimated cost savings of £30 000 per year. CONCLUSION: Non-adherence to MTX can be improved using simple measures including focussing on the adherence and the benefits of treatment, and providing consistent information across departments.
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Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Adesão à Medicação/estatística & dados numéricos , Metotrexato/uso terapêutico , Entrevista Motivacional , Melhoria de Qualidade , Antirreumáticos/sangue , Artrite Reumatoide/sangue , Produtos Biológicos/uso terapêutico , Consultores/estatística & dados numéricos , Redução de Custos , Humanos , Metotrexato/sangue , Educação de Pacientes como Assunto , Indução de Remissão , Autorrelato/estatística & dados numéricos , Inquéritos e Questionários/estatística & dados numéricos , Fatores de TempoRESUMO
Background Supine or prone positioning of the patient on the gantry table is the current standard of care for CT-guided lung biopsy; positioning biopsy side down was hypothesized to be associated with lower pneumothorax rate. Purpose To assess the effect of positioning patients biopsy side down during CT-guided lung biopsy on the incidence of pneumothorax, chest drain placement, and hemoptysis. Materials and Methods This retrospective study was performed between January 2013 and December 2016 in a tertiary referral oncology center. Patients undergoing CT-guided lung biopsy were either positioned in (a) the standard prone or supine position or (b) the lateral decubitus position with the biopsy side down. The relationship between patient position and pneumothorax, drain placement, and hemoptysis was assessed by using multivariable logistic regression models. Results A total of 373 consecutive patients (mean age ± standard deviation, 68 years ± 10), including 196 women and 177 men, were included in the study. Among these patients, 184 were positioned either prone or supine depending on the most direct path to the lesion and 189 were positioned biopsy side down. Pneumothorax occurred in 50 of 184 (27.2%) patients who were positioned either prone or supine and in 20 of 189 (10.6%) patients who were positioned biopsy side down (P < .001). Drain placement was required in 10 of 184 (5.4%) patients who were positioned either prone or supine and in eight of 189 (4.2%) patients who were positioned biopsy side down (P = .54). Hemoptysis occurred in 19 of 184 (10.3%) patients who were positioned prone or supine and in 10 of 189 (5.3%) patients who were positioned biopsy side down (P = .07). Prone or supine patient position (P = .001, odds ratio [OR] = 2.7 [95% confidence interval {CI}: 1.4, 4.9]), emphysema along the needle path (P = .02, OR = 2.1 [95% CI: 1.1, 4.0]), and lesion size (P = .02, OR = 1.0 [95% CI: 0.9, 1.0]) were independent risk factors for developing pneumothorax. Conclusion Positioning a patient biopsy side down for percutaneous CT-guided lung biopsy reduced the incidence of pneumothorax compared with the supine or prone position. © RSNA, 2019.
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Tubos Torácicos/estatística & dados numéricos , Pulmão/patologia , Posicionamento do Paciente/métodos , Pneumotórax/epidemiologia , Radiografia Intervencionista/métodos , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Biópsia Guiada por Imagem/efeitos adversos , Incidência , Pulmão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Postura , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
Objectives: To describe the baseline characteristics of SLE patients requiring biologic therapy in the UK and to explore short term efficacy and infection rates associated with rituximab (RTX) use. Methods: Patients commencing biologic therapy for refractory SLE and who consented to join BILAG-BR were analysed. Baseline characteristics, disease activity (BILAG 2004/SLEDAI-2K) and rates of infection over follow-up were analysed. Response was defined as loss of all A and B BILAG scores to ⩽ 1 B score with no new A/B scores in other organ systems at 6 months. Results: Two hundred and seventy SLE patients commenced biologic therapy from September 2010 to September 2015, most commonly RTX (n = 261). Two hundred and fifty (93%) patients were taking glucocorticoids at baseline at a median [interquartile range (IQR)] oral dose of 10 mg (5-20 mg) daily. Response rates at 6 months were available for 68% of patients. The median (IQR) BILAG score was 15 (10-23) at baseline and 3 (2-12) at 6 months (P < 0.0001). The median (IQR) SLEDAI-2K reduced from 8 (5-12) to 4 (0-7) (P < 0.001). Response was achieved in 49% of patients. There was also a reduction in glucocorticoid use to a median (IQR) dose of 7.5 mg (5-12 mg) at 6 months (P < 0.001). Serious infections occurred in 26 (10%) patients, being more frequent in the first 3 months post-RTX therapy. A higher proportion of early infections were non-respiratory (odds ratio = 1.98, 95% CI: 0.99, 3.9; P = 0.049). Conclusion: RTX is safe and is associated with improvement in disease activity in refractory SLE patients with concomitant reductions in glucocorticoid use. Early vigilance for infection post-infusion is important to further improve treatment risks and benefits.
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Antirreumáticos/administração & dosagem , Produtos Biológicos/administração & dosagem , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Rituximab/administração & dosagem , Adulto , Antirreumáticos/efeitos adversos , Produtos Biológicos/efeitos adversos , Estudos de Casos e Controles , Feminino , Glucocorticoides/uso terapêutico , Humanos , Infecções/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Rituximab/efeitos adversos , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Reino UnidoRESUMO
Endothelial microparticles (EMPs) are endothelium-derived submicron vesicles that are released in response to diverse stimuli and are elevated in cardiovascular disease, which is correlated with risk factors. This study investigates the effect of EMPs on endothelial cell function and dysfunction in a model of free fatty acid (FFA) palmitate-induced oxidative stress. EMPs were generated from TNF-α-stimulated HUVECs and quantified by using flow cytometry. HUVECs were treated with and without palmitate in the presence or absence of EMPs. EMPs were found to carry functional eNOS and to protect against oxidative stress by positively regulating eNOS/Akt signaling, which restored NO production, increased superoxide dismutase and catalase, and suppressed NADPH oxidase and reactive oxygen species (ROS) production, with the involvement of NF-erythroid 2-related factor 2 and heme oxygenase-1. Conversely, under normal conditions, EMPs reduced NO release and increased ROS and redox-sensitive marker expression. In addition, functional assays using EMP-treated mouse aortic rings that were performed under homeostatic conditions demonstrated a decline in endothelium-dependent vasodilatation, but restored the functional response under lipid-induced oxidative stress. These data indicate that EMPs harbor functional eNOS and potentially play a role in the feedback loop of damage and repair during homeostasis, but are also effective in protecting against FFA-induced oxidative stress; thus, EMP function is reflected by the microenvironment.-Mahmoud, A. M., Wilkinson, F. L., McCarthy, E. M., Moreno-Martinez, D., Langford-Smith, A., Romero, M., Duarte, J., Alexander, M. Y. Endothelial microparticles prevent lipid-induced endothelial damage via Akt/eNOS signaling and reduced oxidative stress.
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Micropartículas Derivadas de Células/metabolismo , Endotélio Vascular/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Proteína Oncogênica v-akt/metabolismo , Estresse Oxidativo/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Células Endoteliais/metabolismo , Humanos , Lipídeos/farmacologia , NADPH Oxidases/metabolismo , Vasodilatação/efeitos dos fármacosRESUMO
OBJECTIVE: To evaluate the association between low back pain and bone marrow edema in lumbosacral transitional vertebra (LSTV) transverse processes, and to assess the prevalence of LSTV in a physically active population. MATERIALS AND METHODS: Individuals with LSTV on coronal MRI studies were identified in a retrospective review by keyword search from PACS. In total, 140 cases were reviewed by two fellowship-trained musculoskeletal radiologists. Data on associated low back pain were collected from patient records at the time of the imaging. RESULTS: Bone marrow edema was observed in 44% of the cases, but no correlation with low back pain was found. On coronal MRI, the prevalence of LSTV was 2.6%, with type II LSTV being the most common subtype. CONCLUSIONS: No correlation with bone marrow edema at the transverse processes of the LSTV and low back pain was observed. In our selected study population, the prevalence of LSTV was low.
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Doenças da Medula Óssea/diagnóstico por imagem , Edema/diagnóstico por imagem , Dor Lombar/diagnóstico por imagem , Vértebras Lombares/diagnóstico por imagem , Sacro/diagnóstico por imagem , Adolescente , Adulto , Idoso , Criança , Humanos , Pessoa de Meia-Idade , Radiografia , Estudos Retrospectivos , Adulto JovemRESUMO
Systemic lupus erythematosus (SLE) is a complex disease targeting multiple organs as a result of overactivation of the type I interferon (IFN) system, a feature currently being targeted by multiple biologic therapies against IFN-α. We have identified an estrogen-regulated microRNA, miR-302d, whose expression is decreased in SLE patient monocytes and identify its target as interferon regulatory factor (IRF)-9, a critical component of the transcriptional complex that regulates expression of interferon-stimulated genes (ISGs). In keeping with the reduced expression of miR-302d in SLE patient monocytes, IRF9 levels were increased, as was expression of a number of ISGs including MX1 and OAS1. In vivo evaluation revealed that miR-302d protects against pristane-induced inflammation in mice by targeting IRF9 and hence ISG expression. Importantly, patients with enhanced disease activity have markedly reduced expression of miR-302d and enhanced IRF9 and ISG expression, with miR-302d negatively correlating with IFN score. Together these findings identify miR-302d as a key regulator of type I IFN driven gene expression via its ability to target IRF9 and regulate ISG expression, underscoring the importance of non-coding RNA in regulating the IFN pathway in SLE.
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Regulação da Expressão Gênica , Fator Gênico 3 Estimulado por Interferon, Subunidade gama/genética , Lúpus Eritematoso Sistêmico/genética , MicroRNAs/genética , Interferência de RNA , Animais , Análise por Conglomerados , Modelos Animais de Doenças , Estrogênios/farmacologia , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Interferon Tipo I/metabolismo , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/metabolismo , Camundongos , Monócitos/efeitos dos fármacos , Monócitos/imunologia , Monócitos/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
Background The incidence of thyroid cancer is increasing in men and women. Fine needle aspiration (FNA) is an accepted technique to assess thyroid nodules but is associated with a high rate of non-diagnostic sampling. Purpose To assess the diagnostic performance of ultrasound-guided FNA of thyroid nodules and identify factors associated with non-diagnostic sampling. Material and Methods A retrospective review of thyroid FNAs was performed between 2006 and 2013. Patient demographics, nodule characteristics, procedural technique, cytology, and complications were recorded. Cytology was categorized THY1-5 based on the British Thyroid Association guidelines. Descriptive and multivariable analysis were conducted to identify factors associated with non-diagnostic sampling. Results A total of 724 procedures were identified with 597 (82.5%) in women, and an overall mean age of 40 years (age range, 17-87 years). Factors associated with a non-diagnostic outcome in the multivariable regression analysis included increasing lesion depth (OR, 1.05 per mm; 95% confidence interval [CI], 1.007-1.10), age (OR, 1.012 per year; 95% CI, 1.0-1.025) and number of FNA passes (1 vs. 4+; OR, 6.07; 95% CI, 2.27-16.21). The complication rate was 1.1% related to perilesional hematomas and vaso-vagal episodes. Conclusion Thyroid FNA is a safe and reliable procedure for cytological assessment of thyroid nodules. Deeper nodules and older patients are more likely to have non-diagnostic samples.
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Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/diagnóstico por imagem , Nódulo da Glândula Tireoide/patologia , Ultrassonografia de Intervenção/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Fatores de Confusão Epidemiológicos , Feminino , Humanos , Biópsia Guiada por Imagem , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos Retrospectivos , Adulto JovemRESUMO
Injuries of the hip and surrounding structures represent a complex and commonly encountered scenario in athletes, with improper diagnosis serving as a cause of delayed return to play or progression to a more serious injury. As such, radiologists play an essential role in guiding management of athletic injuries. Familiarity with hip anatomy and the advantages and limitations of various imaging modalities is of paramount importance for accurate and timely diagnosis. Magnetic resonance (MR) imaging is often the modality of choice for evaluating many of the injuries discussed, although preliminary evaluation with conventional radiography and use of other imaging modalities such as ultrasonography (US), computed tomography, and bone scintigraphy may be supplementary or preferred in certain situations. Stress fractures, thigh splints, and posterior hip dislocations are important structural injuries to consider in the athlete, initially imaged with radiographs and often best diagnosed with MR imaging. Apophyseal injuries are particularly important to consider in young athletes and may be acute or related to chronic repetitive microtrauma. Femoroacetabular impingement has been implicated in development of labral tears and cartilage abnormalities. Tear of the ligamentum teres is now recognized as a potential cause of hip pain and instability, best evaluated with MR arthrography. Greater trochanteric pain syndrome encompasses a group of conditions leading to lateral hip pain, with US playing an increasingly important role for both evaluation and image-guided treatment. Muscle injuries and athletic pubalgia are common in athletes. Lastly, snapping hip syndrome and Morel-Lavallée lesions are two less common but nonetheless important considerations. ©RSNA, 2016.
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Traumatismos em Atletas/diagnóstico por imagem , Impacto Femoroacetabular/diagnóstico por imagem , Lesões do Quadril/diagnóstico , Imageamento por Ressonância Magnética/métodos , Lesões dos Tecidos Moles/diagnóstico por imagem , Traumatismos dos Tendões/diagnóstico por imagem , Ultrassonografia/métodos , Artrografia/métodos , Diagnóstico Diferencial , Medicina Baseada em Evidências , Humanos , Aumento da Imagem/métodos , Traumatismo Múltiplo/diagnóstico por imagem , Posicionamento do Paciente/métodosRESUMO
In addition to regulating B cell development and activation, Bruton's tyrosine kinase (Btk) functions downstream of multiple TLRs, including TLR7, to regulate innate immune responses in myeloid cells. Although critical for defense against RNA viruses such as influenza and Sendai virus, recognition of self-RNA by TLR7 also has been shown to be an important contributor to the pathophysiology of systemic lupus erythematosus. To date, the role of Btk in regulating TLR7-mediated responses is poorly understood. In the current study, we have demonstrated a hitherto undiscovered role for Btk in apoptotic cell uptake, identifying the molecular chaperone calreticulin (CRT) as a novel substrate for Btk in regulating this response. CRT together with the transmembrane receptor CD91 function at the cell membrane and regulate uptake of C1q-opsonised apoptotic cells. Our results show that Btk directly phosphorylates CRT and that in the absence of Btk, CRT fails to localize with CD91 at the cell surface and at the phagocytic cup. Critically, a blocking Ab against CRT in wild-type macrophages mimics the inability of Btk-deficient macrophages to phagocytose apoptotic cells efficiently, indicating the critical importance of Btk in regulating CRT-driven apoptotic cell uptake. Our data have revealed a novel regulatory role for Btk in mediating apoptotic cell clearance, with CRT identified as the critical component of the CRT/CD91/C1q system targeted by Btk. Given the importance of clearing apoptotic cell debris to prevent inappropriate exposure of TLRs to endogenous ligands, our results have important implications regarding the role of Btk in myeloid cell function.
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Apoptose , Calreticulina/metabolismo , Complemento C1q/imunologia , Glicoproteínas de Membrana/metabolismo , Proteínas Tirosina Quinases/metabolismo , Receptor 7 Toll-Like/metabolismo , Tirosina Quinase da Agamaglobulinemia , Animais , Anticorpos Bloqueadores/imunologia , Linhagem Celular , Membrana Celular/metabolismo , Proteína-1 Relacionada a Receptor de Lipoproteína de Baixa Densidade , Ativação Linfocitária , Macrófagos/imunologia , Proteínas de Membrana , Camundongos , Células Mieloides/imunologia , Fagocitose/imunologia , Fosforilação , Proteínas Tirosina Quinases/genética , Proteínas Tirosina Quinases/imunologia , Receptores de LDL/metabolismo , Transdução de Sinais , Proteínas Supressoras de Tumor/metabolismoRESUMO
BACKGROUND: Traditionally double J ureteric stents have been removed and replaced via cystoscopy. Fluoroscopically guided procedures for the removal/replacement of stents using endovascular snare devices have previously been described as a successful alternative. PURPOSE: To evaluate the technical and clinical success of fluoroscopically guided transurethral removal and/or replacement of ureteric stents in women. To assess radiation dose and screening time associated with this approach. MATERIAL AND METHODS: A 31-month retrospective review of all ureteric stent removals and/or replacements under fluoroscopic guidance performed in a university hospital radiology department. RESULTS: One hundred and fourteen procedures were performed in 83 patients. Thirty ureteric stents were removed and 84 ureteric stents were replaced. The majority of patients required stents for urinary tract obstruction secondary to malignancy (78.3%). Overall technical and clinical success rates (defined respectively as satisfactory removal/replacement and drainage of the collecting system) of 98.2% were attained. Mean screening time was 13.9 min (range, 1.0-67.6 min). Effective radiation dose was in the range of 0.69-132 mSv with a mean of 11.18 mSv equating to the dose of a contrast-enhanced computed tomography abdomen/pelvis. CONCLUSION: Transurethral ureteric stent removal and replacement under fluoroscopic guidance is highly successful, well tolerated by patients with acceptable radiation exposure, and can obviate the need for cystoscopic retrieval.
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Remoção de Dispositivo/métodos , Radiografia Intervencionista/métodos , Stents , Ureter/diagnóstico por imagem , Ureter/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Fluoroscopia/métodos , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
OBJECTIVE: The aim of this study was to explore the role of cytokines in the pathogenesis of SLE in a genetically homogeneous Caucasian SLE patient population. METHODS: Serum levels of the following cytokines were determined by ELISA in SLE patients (diagnosed as per ACR diagnostic criteria): IL-1ß, IL-10, IL-12p70 and TNF-α. Demographic data, disease activity as per the SLEDAI and damage scores (SLICC) at the 5-year follow-up were calculated. RESULTS: Enhanced production of TNF-α, IL-1 and IL-10 were observed in SLE patients compared with controls. A strong positive correlation was seen between levels of IL-12p70 and IL-10. In addition, IL-10, TNF-α and IL-1 demonstrated a significant relationship with disease activity. Interestingly, elevated levels of IL-10 were observed in SLE patients with CNS involvement while patients with elevated levels of TNF-α were more likely to have renal involvement and sustain damage over the follow-up period. Additionally, the ratio of all cytokines assayed to IL-12p70 levels were significantly higher in SLE patients when compared with controls, with an association seen between damage accrual and the IL-1ß/IL-12p70 ratio (r = 0.431, P = 0.003), IL-10/IL-12p70 ratio (r = 0.351, P = 0.018) and TNF-α/IL-12p70 ratio (r = 0.33, P = 0.028). When the respective ratios were analysed for organ-specific disease, significant differences were observed for the IL-1ß/IL-12p70 ratio (0.79 vs 0.47, P = 0.036), IL-10/IL-12p70 ratio (4.29 vs 1.87, P = 0.018) and TNF-α/IL-12p70 ratio (7.49 vs 5.21, P = 0.018) with respect to renal involvement. CONCLUSION: Increased levels of a number of immunomodulatory cytokines relative to IL-12p70 in this Caucasian SLE patient population are seen in patients with renal involvement and are associated with increased accrual of damage at the 5-year follow-up.
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Citocinas/sangue , Lúpus Eritematoso Sistêmico/imunologia , Índice de Gravidade de Doença , Adulto , Fatores Etários , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Humanos , Mediadores da Inflamação/metabolismo , Interleucina-10/biossíntese , Interleucina-12/sangue , Masculino , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/biossínteseRESUMO
Inflammatory arthritis are common chronic inflammatory autoimmune diseases characterised by progressive, destructive inflammation of the joints leading to a loss of function and significant comorbidities; importantly, there are no cures and only 20% of patients achieve drug-free remission for over 2 years. Macrophages play a vital role in maintaining homeostasis, however, under the wrong environmental cues, become drivers of chronic synovial inflammation. Based on the current "dogma", M1 macrophages secrete pro-inflammatory cytokines and chemokines, promoting tissue degradation and joint and bone erosion which over time lead to accelerated disease progression. On the other hand, M2 macrophages secrete anti-inflammatory mediators associated with wound healing, tissue remodelling and the resolution of inflammation. Currently, four subtypes of M2 macrophages have been identified, namely M2a, M2b, M2c and M2d. However, more subtypes may exist due to macrophage plasticity and the ability for repolarisation. Macrophages are highly plastic, and polarisation exists as a continuum with diverse intermediate phenotypes. This plasticity is achieved by a highly amenable epigenome in response to environmental stimuli and shifts in metabolism. Initiating treatment during the early stages of disease is important for improved prognosis and patient outcomes. Currently, no treatment targeting macrophages specifically is available. Such therapeutics are being investigated in ongoing clinical trials. The repolarisation of pro-inflammatory macrophages towards the anti-inflammatory phenotype has been proposed as an effective approach in targeting the M1/M2 imbalance, and in turn is a potential therapeutic strategy for IA diseases. Therefore, elucidating the mechanisms that govern macrophage plasticity is fundamental for the success of novel macrophage targeting therapeutics.
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Plasticidade Celular , Macrófagos , Humanos , Macrófagos/metabolismo , Macrófagos/imunologia , Animais , Inflamação/patologia , Artrite/imunologia , Artrite/patologiaRESUMO
OBJECTIVE: The overall aim of this study was to establish whether plasma fibrinogen was a superior biomarker of disease activity in active PMR than the standard biomarkers, ESR and CRP. METHODS: Sixty patients with PMR were divided into active (n = 25) or inactive (n = 35) disease groups based on symptoms, physician assessment and biomarkers ESR and CRP. Plasma fibrinogen was assayed. Groups underwent assessment at baseline and 6 weeks. Disease activity as per the PMR activity score (PMR-AS) was recorded at all visits. Receiver operator curves (ROCs), predictive values and likelihood ratios were calculated for all biomarkers. RESULTS: Disease activity measures improved significantly in the active group between weeks 1 and 6 (P < 0.001). There was no significant difference between the activity scores at week 6 in the active group and the inactive group. Mean fibrinogen decreased from 5.2 to 3.5 g/l (normal <4 g/l) between weeks 1 and 6 in the active group. Mean ESR and CRP decreased from 59.6 to 24.3 mm/h (normal <30 mm/h) and 45.9 to 12.66 mg/l (normal <5 mg/l), respectively. Receiver operator curve analysis revealed fibrinogen to be more specific than either ESR or CRP for the detection of response to treatment in active PMR, with an overall sensitivity and specificity of 92% and 96%, respectively. Values above the upper limit of normal for fibrinogen, CRP and ESR were associated with likelihood ratios for active disease of 20.53, 2.9 and 2.8, respectively (P < 0.001). CONCLUSION: Plasma fibrinogen is at least as useful as CRP and ESR for the diagnosis of active PMR and more specific for confirmation of response to treatment than either ESR or CRP.
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Fibrinogênio/análise , Polimialgia Reumática/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/análise , Biomarcadores/metabolismo , Sedimentação Sanguínea , Proteína C-Reativa/metabolismo , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Curva ROCRESUMO
OBJECTIVE: The overall aim of this study is to identify clinical and serological features that are associated with B lymphocyte stimulator (BLyS) elevation in a homogeneous Caucasian SLE population and thereby identify patients who are most likely to benefit from BLyS blockade. METHODS: Patients with SLE (as per ACR criteria) were recruited. Clinical history, disease activity measures and laboratory measures of disease were recorded. BLyS levels were determined by ELISA. RESULTS: BLyS elevation was defined as being higher than the 95th percentile of BLyS levels measured in controls. Patients were divided into two groups: those with elevated BLyS levels (group 1, n = 23) and those with normal BLyS levels (group 2, n = 22). Elevated BLyS levels were significantly associated with patients of younger age and shorter disease duration. In keeping with previous reports, patients with elevated BLyS levels had more active disease (SLEDAI 5.1 vs 0.86, P < 0.001); however, our analysis also demonstrates that BLyS elevation was significantly associated with increased organ damage at 5-year follow-up [Systemic Lupus International Collaborating Clinics/ACR Damage Index (SLICC/ACR DI) 0.53 vs 0.13, P = 0.012]. Furthermore, the presence of Sm autoantibody significantly predicted elevated BLyS levels in a Caucasian population. BLyS levels were significantly higher in those with musculoskeletal involvement, malar rash, renal disease and evidence of immunological activity. CONCLUSION: BLyS blockade may be most beneficial if introduced early in the course of disease in young Caucasian patients presenting with renal, musculoskeletal and skin disease in an effort to reduce long-term damage.
Assuntos
Fator Ativador de Células B/sangue , Lúpus Eritematoso Sistêmico/imunologia , Índice de Gravidade de Doença , Adulto , Fatores Etários , Autoanticorpos/sangue , Estudos de Casos e Controles , Estudos de Coortes , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Irlanda , Masculino , Pessoa de Meia-Idade , Projetos PilotoRESUMO
BACKGROUND: Endoscopic sphincterotomy is an integral component of endoscopic retrograde cholangiopancreatography. Post-sphincterotomy hemorrhage is a recognized complication. First line treatment involves a variety of endoscopic techniques performed at the time of sphincterotomy. If these are not successful, transcatheter arterial embolization or open surgical vessel ligation are therapeutic considerations. PURPOSE: To evaluate the technical and clinical success of transcatheter arterial embolization via micro coils in the management of bleeding post-endoscopic sphincterotomy (ES). MATERIAL AND METHODS: An 8-year retrospective review of all patients referred for transcatheter arterial embolization (TAE) for management of post-ES bleeding not controlled by endoscopy was performed. We analyzed the findings at endoscopy, angiography, interventional procedure, and the technical and clinical success. RESULTS: Twelve embolization procedures were performed in 11 patients. Technical success was achieved in 11 of 12 procedures. Branches embolized included the gastroduodenal artery (GDA) in 11 cases, the superior pancreaticoduodenal artery (SPDA) in one case, and the inferior pancreaticoduodenal artery (IPDA) in four cases. Clinical success was achieved in 10 of 11 patients. One patient was referred for surgical intervention due to rebleeding from the IPDA. CONCLUSION: Our experience demonstrates that TAE can effectively control bleeding post-ES avoiding the need for invasive surgery in most patients.
Assuntos
Embolização Terapêutica/métodos , Hemorragia Pós-Operatória/terapia , Esfinterotomia Endoscópica , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Hemorragia Gastrointestinal/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Radiografia Intervencionista , Resultado do TratamentoRESUMO
BACKGROUND: Patients with inflammatory arthritis are at increased risk of infection. Much of the burden of infection in this population is vaccine preventable. A number of international rheumatology organizations have published expert recommendations for vaccination in adult patients. Despite this, reported vaccination rates remain low among patients with inflammatory arthritis. OBJECTIVES: We sought to establish the knowledge, attitudes, and clinical practice of rheumatologists with respect to vaccination. METHODS: Rheumatologists practicing in Ireland in 2009 were surveyed by postal questionnaire. Data collected was entered into Microsoft Excel and statistical analysis was carried out using SPSS18 software. RESULTS: Eighty (100%) practicing rheumatologists were surveyed. Response rate was 55% (44/80). Of those surveyed, 57% (25/44) had no written departmental vaccination guidelines. Although 90% of those surveyed agreed that the responsibility for ensuring vaccine compliance rests with health professionals, only 5% considered that the rheumatology clinic was the best setting in which to accomplish this. Half (50%, n = 22) of practicing rheumatologists do not inquire about vaccination history in the clinic, with a minority (9%, n = 4) recording vaccination history in their clinical notes. A significant percentage of rheumatologists do not perform screening about prior vaccination before initiation of either anti-tumor necrosis factor (34%) or disease-modifying antirheumatic disease (42%) therapy. Moreover, 57% (n = 25) considered the responsibility for vaccination the domain of the patients' general practitioners with the favored strategy to improve vaccine compliance being led by the primary care physicians (48%, n = 21). CONCLUSIONS: The practice of Irish rheumatologists with regard to vaccination in this survey was suboptimal. Most neither recommend nor record vaccination history in their clinical notes, with the majority feeling that the rheumatology clinic is not the appropriate setting in which to target strategies to improve vaccine compliance. Although a more proactive role needs to be taken by rheumatologists as the principal prescribers of immunosuppressive therapy on this issue, our survey respondents suggest that strategies to improve vaccine uptake should be developed outside the rheumatology clinic and, in particular, involve primary care. The circulation of currently available international guidelines on vaccination specific for rheumatology patients to primary care physicians should be used to inform practices to ensure improved vaccine compliance.