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1.
Rheumatology (Oxford) ; 62(4): 1621-1626, 2023 04 03.
Artículo en Inglés | MEDLINE | ID: mdl-36124987

RESUMEN

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.


Asunto(s)
COVID-19 , Nacimiento Prematuro , Enfermedades Reumáticas , Embarazo , Recién Nacido , Femenino , Humanos , Vacunas contra la COVID-19 , COVID-19/epidemiología , COVID-19/prevención & control , Prueba de COVID-19 , Enfermedades Reumáticas/tratamiento farmacológico , Vacunación
3.
BMC Rheumatol ; 6(1): 16, 2022 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-35331328

RESUMEN

BACKGROUND: Culture-negative infective endocarditis (IE) constitutes approximately 10% of all cases of IE. Bartonella endocarditis is a common cause of culture-negative endocarditis and is associated with a high mortality rate. To date, no cases of Bartonella IE has been reported in association with cryoglobulinemia in the UK. We present a unique case of Bartonella IE causing secondary cryoglobulinemia in a young female. CASE PRESENTATION: A 17-year-old female with a background of pulmonary atresia and ventricular septal defect repaired with a cardiac conduit at the age of 4, presented with a one-year history of weight loss (from 53 to 39 kg) and poor appetite. She subsequently developed a vasculitic rash and haematoproteinuria with decline in renal function, requiring urgent hospital admission. Initial blood tests showed a near normal creatinine, but a raised cystatin C. Renal biopsy showed focal necrotizing glomerulonephritis with no acute tubular necrosis or chronic change. Subsequent blood tests supported a diagnosis of cryoglobulinaemic vasculitis (high rheumatoid factor, low complement, polyclonal gammopathy, Type 3 cryoglobulin). A weak positive PR3 meant there was some uncertainty about whether this could be a primary ANCA-associated vasculitis (AAV). Initial workup for an infectious cause, including multiple blood cultures, were negative. However, an echocardiogram showed definite vegetations on her surgical conduit. The patient did not respond to empirical antimicrobials and so was referred for surgical revision of her conduit. Tissue samples obtained intra-operatively demonstrated Bartonella species. With targeted antimicrobials post-operatively, she improved with resolution of immunologic abnormalities and at last review had a normal renal profile. On reviewing her social history, she had adopted several stray cats in the preceding year; and thus, the cause of the Bartonella infection was identified. CONCLUSION: This is the first reported case of Bartonella endocarditis causing secondary cryoglobulinemia reported in the UK. The key learning points from this case include that Bartonella endocarditis can present as a cryoglobulinaemic vasculitis and should be considered in any differential when the cause of cryoglobulinaemia is not clear and to enquire about relevant exposures especially when culture-negative endocarditis is suspected.

4.
J Rheumatol ; 49(1): 110-114, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34470798

RESUMEN

OBJECTIVE: To describe coronavirus disease 2019 (COVID-19) and pregnancy outcomes in patients with rheumatic disease who were pregnant at the time of infection. METHODS: Since March 2020, the COVID-19 Global Rheumatology Alliance has collected cases of patients with rheumatic disease with COVID-19. We report details of pregnant women at the time of COVID-19 infection, including obstetric details separately ascertained from providers. RESULTS: We report on 39 patients, including 22 with obstetric detail available. The mean and median age was 33 years, range 24-45 years. Rheumatic disease diagnoses included rheumatoid arthritis (n = 9), systemic lupus erythematosus (n = 9), psoriatic arthritis/other inflammatory arthritides (n = 8), and antiphospholipid syndrome (n = 6). Most had a term birth (16/22), with 3 preterm births, 1 termination, and 1 miscarriage; 1 woman had yet to deliver at the time of report. One-quarter (n = 10/39) of pregnant women were hospitalized following COVID-19 diagnosis. Two of 39 (5%) required supplemental oxygen (both hospitalized); no patients died. The majority did not receive specific medication treatment for their COVID-19 (n = 32/39, 82%), and 7 patients received some combination of antimalarials, colchicine, anti-interleukin 1ß, azithromycin, glucocorticoids, and lopinavir/ritonavir. CONCLUSION: Women with rheumatic diseases who were pregnant at the time of COVID-19 had favorable outcomes. These data have limitations due to the small size and methodology; however, they provide cautious optimism for pregnancy outcomes for women with rheumatic disease particularly in comparison to the increased risk of poor outcomes that have been reported in other series of pregnant women with COVID-19.


Asunto(s)
COVID-19 , Enfermedades Reumáticas , Reumatología , Adulto , Prueba de COVID-19 , Femenino , Humanos , Recién Nacido , Persona de Mediana Edad , Embarazo , Mujeres Embarazadas , Enfermedades Reumáticas/terapia , SARS-CoV-2 , Adulto Joven
5.
Lupus Sci Med ; 8(1)2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-34301852

RESUMEN

OBJECTIVE: To quantify how well phase III randomised clinical trials in both SLE and lupus nephritis (LN) represents a real-world SLE cohort. METHODS: Literature reviews were performed of major published phase III SLE (n=12) and LN (n=6) clinical trials (ClinicalTrials.gov). Inclusion and exclusion criteria common across these trials were collated for non-renal SLE or LN trials, and applied to patients recruited to the British Isles Lupus Assessment Group-Biologics Register (BILAG-BR) starting either biological or standard-of-care (SOC) therapies. RESULTS: We recruited 837 patients to the BILAG-BR from September 2010 to June 2018, starting either SOC (n=125, 15%) or a biological medication (n=712, 85%). Active LN, defined as a BILAG A in the renal domain occurred in 20% (n=166). Overall, 530 (63%) patients were ineligible to participate in non-renal SLE clinical trials and 72 (43%) patients with active LN would be ineligible for LN trials. The most common reasons for ineligibility from the non-renal lupus trials included active renal involvement (n=166, 20%) and low disease activity (n=114, 15%). For LN trials, the most common exclusion met was pre-existing renal impairment (n=15, 9%). Patients with fewer comorbidities were more likely to be eligible to participate in non-renal SLE trials. CONCLUSIONS: In this national register of patients with moderate-to-severe SLE, nearly two-thirds would not be eligible for recruitment to key SLE clinical trials nor would almost half of those with active LN. Eligibility criteria may excessively constrain enrolment and thus, how we can generalise trial results in a real-world setting.


Asunto(s)
Productos Biológicos , Nefritis Lúpica , Ensayos Clínicos como Asunto , Estudios de Cohortes , Humanos , Riñón , Nefritis Lúpica/diagnóstico , Reino Unido/epidemiología
6.
Rheumatology (Oxford) ; 60(1): 125-131, 2021 01 05.
Artículo en Inglés | MEDLINE | ID: mdl-32596718

RESUMEN

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.


Asunto(s)
Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Cumplimiento de la Medicación/estadística & datos numéricos , Metotrexato/uso terapéutico , Entrevista Motivacional , Mejoramiento de la Calidad , Antirreumáticos/sangre , Artritis Reumatoide/sangre , Productos Biológicos/uso terapéutico , Consultores/estadística & datos numéricos , Ahorro de Costo , Humanos , Metotrexato/sangre , Educación del Paciente como Asunto , Inducción de Remisión , Autoinforme/estadística & datos numéricos , Encuestas y Cuestionarios/estadística & datos numéricos , Factores de Tiempo
7.
Arthritis Res Ther ; 21(1): 147, 2019 06 14.
Artículo en Inglés | MEDLINE | ID: mdl-31200750

RESUMEN

OBJECTIVES: To investigate the relationships between interferon alpha (IFNα) and the clinical and serological phenotype of patients with systemic autoimmune rheumatic disease (SARDs) in order to determine whether a distinct subpopulation of patients can be identified. METHODS: We recruited patients with at least 1 SARD clinical feature and at least 1 SARD-related autoantibody from two NHS Trusts in Greater Manchester. A 6-gene interferon-stimulated gene (ISG) score was calculated in all patients, and in a subgroup, a 30-gene ISG score was produced using NanoString. A digital Single Molecule Array (Simoa) was used to measure plasma IFNα protein. In an exploratory analysis, whole blood RNA sequencing was conducted in 12 patients followed by RT-qPCR confirmation of expression of 6 nucleic acid receptors (NARs) in the whole cohort. RESULTS: Sixty three of 164 (38%) patients had a positive ISG score. The 3 measures of IFNα all correlated strongly with each other (p < 0.0001). There were no differences in mucocutaneous or internal organ involvement between the ISG subgroups. The ISG-positive group had increased frequency of specific autoantibodies and haematological abnormalities which remained significant after adjusting for the SARD subtype. Expression of DDX58, MB21D1 and TLR7 was correlated with the ISG score whilst TLR3, TLR9 and MB21D1 were associated with neutrophil count. CONCLUSION: In SARD patients, IFNα-positivity was associated with specific autoantibodies and haematological parameters but not with other clinical features. The variable NAR expression suggests that different pathways may drive IFNα production in individual patients. The identification of an IFNα-positive subgroup within a mixed SARD cohort supports a pathology-based approach to treatment.


Asunto(s)
Autoanticuerpos/sangre , Enfermedades Autoinmunes/inmunología , Interferón Tipo I/sangre , Enfermedades Reumáticas/inmunología , Adulto , Autoanticuerpos/inmunología , Enfermedades Autoinmunes/sangre , Biomarcadores/sangre , Femenino , Humanos , Interferón Tipo I/inmunología , Interferón-alfa/sangre , Interferón-alfa/inmunología , Masculino , Persona de Mediana Edad , Enfermedades Reumáticas/sangre , Transcriptoma/genética , Adulto Joven
8.
Radiology ; 292(1): 190-196, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-31084480

RESUMEN

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.


Asunto(s)
Tubos Torácicos/estadística & datos numéricos , Pulmón/patología , Posicionamiento del Paciente/métodos , Neumotórax/epidemiología , Radiografía Intervencional/métodos , Tomografía Computarizada por Rayos X/métodos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Biopsia Guiada por Imagen/efectos adversos , Incidencia , Pulmón/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Postura , Estudios Retrospectivos , Factores de Riesgo , Adulto Joven
9.
Lupus Sci Med ; 5(1): e000272, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30167314

RESUMEN

OBJECTIVE: 10-year cardiovascular disease (CVD) risk scores are calculated using algorithms, including Framingham (worldwide) and QRISK2 (UK). Recently, an updated QRISK3 model was introduced, which considers new variables including SLE and steroid prescription, not included in QRISK2 and Framingham algorithms. We sought to determine the extent to which QRISK3 improves identification of high-risk patients with SLE and whether the score relates to standard and novel markers of SLE-specific endothelial dysfunction. METHODS: Framingham and QRISK2/3 scores were calculated in patients with SLE (n=109) and healthy controls (n=29) using clinical measures. In a smaller cohort (n=58), markers of inflammation and endothelial dysfunction, including CD144+ endothelial microvesicles (EMVs), triglycerides, vascular cell adhesion molecule (VCAM) and high-sensitivity C reactive protein (hsCRP) were quantified by flow cytometry and ELISA, respectively. RESULTS: Patients with SLE demonstrated significantly higher QRISK3 scores than controls (5.0%vs0.3%, p<0.001). 21/109 patients with SLE (19%) and 24/109(22%) were newly identified as being at high risk of a CV event when using QRISK3 versus QRISK2 (29vs8patients) and QRISK3 versus Framingham (29vs5patients; p<0.001), respectively. These 'new QRISK3' patients with SLE were more likely to have lupus nephritis, be anticardiolipin antibody positive, currently prescribed corticosteroids, had a higher Body Mass Index and systolic blood pressure (BP) than low-risk patients with SLE. Rates of antiplatelet (8/21) and statin use (5/21) were low in the new QRISK3 group. EMVs, hsCRP and triglyceride levels were significantly higher in new QRISK3 patientscompared with low-risk patients with SLE (p<0.05). Furthermore, pulse wave velocity and VCAM were significantly elevated in all high versus low QRISK3 patients. CONCLUSIONS: QRISK3 captures significantly more patients with SLE with an elevated 10-year risk of developing CVD, which is associated with measures of endothelial dysfunction; EMVs and systolic BP. The adoption of QRISK3 will enhance management of CVD risk in patients with SLE for improved outcome.

10.
JCI Insight ; 3(15)2018 08 09.
Artículo en Inglés | MEDLINE | ID: mdl-30089723

RESUMEN

Severe lung inflammation and alveolar hemorrhage can be life-threatening in systemic lupus erythematosus (SLE) patients if not treated early and aggressively. Neutrophil influx is the driver key of this pathology, but little is known regarding the molecular events regulating this recruitment. Here, we uncover a role for IL-16/mir-125a in this pathology and show not only that IL-16 is a target for miR-125a but that reduced miR-125a expression in SLE patients associates with lung involvement. Furthermore, in the pristane model of acute "SLE-like" lung inflammation and alveolar hemorrhage, we observed reduced pulmonary miR-125a and enhanced IL-16 expression. Neutrophil infiltration was markedly reduced in the peritoneal lavage of pristane-treated IL-16-deficient mice and elevated following i.n. delivery of IL-16. Moreover, a miR-125a mimic reduced pristane-induced IL-16 expression and neutrophil recruitment and rescued lung pathology. Mechanistically, IL-16 acts directly on the pulmonary epithelium and markedly enhances neutrophil chemoattractant expression both in vitro and in vivo, while the miR-125a mimic can prevent this. Our results reveal a role for miR-125a/IL-16 in regulating lung inflammation and suggest this axis may be a therapeutic target for management of acute lung injury in SLE.


Asunto(s)
Interleucina-16/genética , Pulmón/inmunología , Lupus Eritematoso Sistémico/inmunología , MicroARNs/metabolismo , Neumonía/inmunología , Adulto , Animales , Línea Celular , Modelos Animales de Enfermedad , Epitelio/inmunología , Epitelio/patología , Femenino , Regulación de la Expresión Génica/inmunología , Humanos , Interleucina-16/inmunología , Pulmón/citología , Pulmón/efectos de los fármacos , Pulmón/patología , Lupus Eritematoso Sistémico/complicaciones , Macrófagos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , MicroARNs/inmunología , Persona de Mediana Edad , Infiltración Neutrófila/inmunología , Neutrófilos/inmunología , Neumonía/inducido químicamente , Neumonía/patología , Cultivo Primario de Células , Terpenos/administración & dosificación , Terpenos/inmunología
11.
Arthritis Res Ther ; 20(1): 173, 2018 08 09.
Artículo en Inglés | MEDLINE | ID: mdl-30092845

RESUMEN

BACKGROUND: Patients with SLE display marked clinical and immunlogical heterogeneity. The purpose of the study was to investigate patterns of serum cytokines in patients with active and stable systemic lupus erythematosus (SLE) and to determine how they relate to clinical phenotype. METHODS: Serum levels of 10 cytokines were measured retrospectively in a cohort of patients with SLE and in healthy controls using a high-sensitivity multiplex bead array. Disease activity was determined using the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and British Isles Lupus Assessment Group (BILAG-2004) indices. Logistic regression models were used to determine the association between cytokine levels and active SLE. Principal component analysis (PCA) and cluster analysis was then used to identify subgroups of patients on the basis of cytokine levels. RESULTS: Serum chemokine (C-X-C motif) ligand 10 (CXCL10) and CXCL13 were significantly higher in patients with SLE compared to healthy controls. Two cytokines (pentraxin-related protein (PTX3) and CXCL10) were significantly higher in patients with active disease after adjustment for potential confounding factors. Measurement of four cytokines (CXCL10, IL-10, IL-21 and PTX3) significantly improved the performance of a model to identify patients with clinically active disease. Cluster analysis revealed that the patients formed 3 distinct groups, characterised by higher levels of interferon alpha (IFNα) and B lymphocyte stimulator (BLyS) (group 1), increased CXCL10 and CXCL13 (group 2) or low levels of cytokines (group 3). Group 2 had significantly lower serum complement and higher anti-double-stranded DNA antibodies and increased prevalence of inflammatory arthritis. CONCLUSIONS: Multiplex analysis has identified a serum cytokine signature for active SLE. Within the SLE population distinct cytokine subgroups were identified, with differing clinical and immunological phenotypes that appeared stable over time. Assessment of cytokine profiles may reveal unique insights into disease heterogeneity.


Asunto(s)
Citocinas/sangre , Citocinas/inmunología , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/inmunología , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
12.
Skeletal Radiol ; 47(8): 1145-1149, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-29453618

RESUMEN

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.


Asunto(s)
Enfermedades de la Médula Ósea/diagnóstico por imagen , Edema/diagnóstico por imagen , Dolor de la Región Lumbar/diagnóstico por imagen , Vértebras Lumbares/diagnóstico por imagen , Sacro/diagnóstico por imagen , Adolescente , Adulto , Anciano , Niño , Humanos , Persona de Mediana Edad , Radiografía , Estudios Retrospectivos , Adulto Joven
13.
Rheumatology (Oxford) ; 57(3): 470-479, 2018 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-29216396

RESUMEN

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.


Asunto(s)
Antirreumáticos/administración & dosificación , Productos Biológicos/administración & dosificación , Lupus Eritematoso Sistémico/tratamiento farmacológico , Rituximab/administración & dosificación , Adulto , Antirreumáticos/efectos adversos , Productos Biológicos/efectos adversos , Estudios de Casos y Controles , Femenino , Glucocorticoides/uso terapéutico , Humanos , Infecciones/inducido químicamente , Masculino , Persona de Mediana Edad , Rituximab/efectos adversos , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del Tratamiento , Reino Unido
14.
Lupus Sci Med ; 4(1): e000173, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-29238601

RESUMEN

BACKGROUND: The definition of remission in systemic lupus erythematosus (SLE) remains unclear, especially how background treatment should be interpreted. OBJECTIVE: To determine preferences of clinicians in treatment of patients in clinical remission from SLE and to assess how previous severity, duration of remission and serology influence changes in treatment. METHODS: We undertook an internet-based survey of clinicians managing patients with SLE. Case scenarios were constructed to reflect different remission states, previous organ involvement, serological abnormalities, duration of remission and current treatment (hydroxychloroquine (HCQ), steroids and/or immunosuppressive (ISS) agents). RESULTS: 130 clinicians from 30 countries were surveyed. The median (range) duration of practice and number of patients with SLE seen each month was 13 (2-42) years and 30 (2-200), respectively. Management decisions in all scenarios varied with greater caution in treatment reduction with shorter duration of remission, extent of serological abnormalities and previous disease severity. Even with mild disease, normal serology and a 5-year clinical remission, 113 (86.9%) clinicians continue to prescribe HCQ. Persistent abnormal serology in any scenario led to a reluctance to reduce or discontinue medications. Prescribing in remission, particularly of steroids and HCQ, varied significantly according to geographical location. CONCLUSIONS: Clinicians preferences in withdrawing or reducing treatment in patients with SLE in clinical remission vary considerably. Serological abnormalities, previous disease severity and duration of remission all influence the decision to reduce treatment. It is unusual for clinicians to stop HCQ even after prolonged periods of clinical remission. Any definition(s) of remission needs to take into consideration such evidence on how maintenance treatments are managed.

15.
FASEB J ; 31(10): 4636-4648, 2017 10.
Artículo en Inglés | MEDLINE | ID: mdl-28687612

RESUMEN

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.


Asunto(s)
Micropartículas Derivadas de Células/metabolismo , Endotelio Vascular/metabolismo , Óxido Nítrico Sintasa de Tipo III/metabolismo , Proteína Oncogénica v-akt/metabolismo , Estrés Oxidativo/fisiología , Especies Reactivas de Oxígeno/metabolismo , Células Endoteliales/metabolismo , Humanos , Lípidos/farmacología , NADPH Oxidasas/metabolismo , Vasodilatación/efectos de los fármacos
18.
J Autoimmun ; 79: 105-111, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-28318807

RESUMEN

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.


Asunto(s)
Regulación de la Expresión Génica , Subunidad gamma del Factor 3 de Genes Estimulados por el Interferón/genética , Lupus Eritematoso Sistémico/genética , MicroARNs/genética , Interferencia de ARN , Animales , Análisis por Conglomerados , Modelos Animales de Enfermedad , Estrógenos/farmacología , Perfilación de la Expresión Génica , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Interferón Tipo I/metabolismo , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/metabolismo , Ratones , Monocitos/efectos de los fármacos , Monocitos/inmunología , Monocitos/metabolismo , Transducción de Señal/efectos de los fármacos
19.
Acta Radiol ; 58(3): 301-306, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-27329396

RESUMEN

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.


Asunto(s)
Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/patología , Nódulo Tiroideo/diagnóstico por imagen , Nódulo Tiroideo/patología , Ultrasonografía Intervencional/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Factores de Confusión Epidemiológicos , Femenino , Humanos , Biopsia Guiada por Imagen , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Estudios Retrospectivos , Adulto Joven
20.
BJR Case Rep ; 3(4): 20170025, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-30363221

RESUMEN

Ascites is well-documented sequelae of liver cirrhosis with significant impact on survival in this group of patients. Among the many established management strategies for the same is the use of an implantable mechanical device, called alfapump® (Sequana Medical, Zurich, Switzerland), that removes ascitic fluid by pumping it from the peritoneal cavity to the urinary bladder. Until recently, this device has been surgically placed under general anaesthesia. We describe successful interventional radiological implantation under conscious sedation in three patients with minimal complications. This device can serve as an alternative to transjugular intrahepatic portosystemic shunt for the management of refractory ascites; however, further studies are required to understand the device better.

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