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1.
Clin Radiol ; 76(1): 81.e1-81.e10, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-32958223

RESUMEN

AIM: To assess whether magnetic resonance imaging (MRI)-based measurements of T2, fat fraction, diffusion tensor imaging, and muscle volume can detect differences between the muscles of myositis patients and healthy controls, and to identify how they compare with semi-quantitative MRI diagnosis. MATERIALS AND METHODS: Sixteen myositis patients and 16 age- and gender-matched healthy controls underwent MRI of their thigh. Quantitative MRI measurements and radiologists' semi-quantitative scores were assessed. Strength was assessed using an isokinetic dynamometer. RESULTS: Fat fraction and T2 values were higher in myositis patients whereas muscle volume was lower compared to healthy controls. There was no difference in diffusion. Muscle strength was lower in myositis patients compared to healthy controls. In a subgroup of eight patients, scored as unaffected by radiologists, T2 values were still significantly higher in myositis patients. CONCLUSIONS: Quantitative MRI measurements can detect differences between myositis patients and healthy controls. Changes in the muscles of myositis patients, undetected by visual, semi-quantitative scoring, can be detected using quantitative T2 measurements. This suggests that MRI T2 values may be useful for the management of myositis patients.


Asunto(s)
Imagen por Resonancia Magnética/métodos , Miositis/diagnóstico por imagen , Estudios de Casos y Controles , Imagen de Difusión Tensora , Femenino , Voluntarios Sanos , Humanos , Masculino , Persona de Mediana Edad
2.
Aging Clin Exp Res ; 33(2): 291-301, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32198628

RESUMEN

BACKGROUND: Skeletal muscles undergo changes with ageing which can cause sarcopenia that can result in frailty. Quantitative MRI may detect the muscle-deficit component of frailty which could help improve the understanding of ageing muscles. AIMS: To investigate whether quantitative MRI measures of T2, fat fraction (FF), diffusion tensor imaging and muscle volume can detect differences within the muscles between three age groups, and to assess how these measures compare with frailty index, gait speed and muscle power. METHODS: 18 'young' (18-30 years), 18 'middle-aged' (31-68 years) and 18 'older' (> 69 years) healthy participants were recruited. Participants had an MRI of their dominant thigh. Knee extension and flexion power and handgrip strength were measured. Frailty (English Longitudinal Study of Ageing frailty index) and gait speed were measured in the older participants. RESULTS: Young participants had a lower muscle MRI T2, FF and mean diffusivity than middle-aged and older participants; middle-aged participants had lower values than older participants. Young participants had greater muscle flexion and extension power, muscle volume and stronger hand grip than middle-aged and older participants; middle-aged participants had greater values than the older participants. Quantitative MRI measurements correlated with frailty index, gait speed, grip strength and muscle power. DISCUSSION: Quantitative MRI and strength measurements can detect muscle differences due to ageing. Older participants had raised T2, FF and mean diffusivity and lower muscle volume, grip strength and muscle power. CONCLUSIONS: Quantitative MRI measurements correlate with frailty and muscle function and could be used for identifying differences across age groups within muscle.


Asunto(s)
Fragilidad , Sarcopenia , Anciano , Envejecimiento , Imagen de Difusión Tensora , Fragilidad/diagnóstico por imagen , Fuerza de la Mano , Humanos , Estudios Longitudinales , Imagen por Resonancia Magnética , Persona de Mediana Edad , Fuerza Muscular , Músculo Esquelético/diagnóstico por imagen , Sarcopenia/diagnóstico por imagen
3.
Lupus ; 28(11): 1320-1328, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31522626

RESUMEN

OBJECTIVES: The objectives of this study were to assess the reliability of a novel objective outcome measure, laser Doppler imaging (LDI), its validity against skin biopsy histology and other clinical instruments, including localized cutaneous lupus disease area and severity index (L-CLASI) and visual analogue scale (VAS) score of photographs, and its responsiveness to clinical change with therapy. METHODS: A prospective observational cohort study was conducted in 30 patients with active cutaneous lupus erythematosus (CLE). At baseline and 3 months, disease activity was assessed using L-CLASI and a high resolution LDI system by two assessors. Skin biopsy was scored as 0 = non-active, 1 = mild activity and 2 = active. Photographs were assessed by two clinicians using 100 mm VAS. Inter-rater reliability was analyzed using Bland-Altman limits of agreement. Correlation between histology and LDI, L-CLASI and VAS and sensitivity to change of LDI with physician subjective assessment of change (PSAC) at 3 months were analyzed using Kendall's tau-a. RESULTS: Of 30 patients with CLE, 28 (93%) were female, mean (SD) age 48.4 (11.5) y, 25 (83%) were Caucasians, 25 (83%) had concurrent systemic lupus erythematosus and 16 (53%) were smokers. CLE subtypes were acute = 9, subacute = 8 and chronic = 13. Inter-rater agreement for LDI was fair but for VAS score of photographs was poor. In 20 patients with biopsy, correlation with histology was better for LDI (tau-a = 0.53) than L-CLASI (tau-a = 0.26) (difference = 0.27; 90% CI 0.05-0.49) or VAS score of photographs (tau-a = 0.17) (difference = 0.36; 90% CI 0.04-0.68). There was a moderate correlation between PSAC score and change in LDI (tau-a = 0.56; 90% CI 0.38-0.74; p < 0.001, n = 15). CONCLUSION: LDI provides a reliable, valid and responsive quantitative measure of inflammation in CLE. It has a better correlation with histology compared to clinical instruments. LDI provides an objective outcome measure for clinical trials.


Asunto(s)
Flujometría por Láser-Doppler , Lupus Eritematoso Cutáneo/diagnóstico por imagen , Lupus Eritematoso Sistémico/diagnóstico por imagen , Evaluación de Resultado en la Atención de Salud , Adulto , Biopsia , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Estudios Prospectivos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
4.
Osteoarthritis Cartilage ; 26(10): 1333-1337, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-30017726

RESUMEN

OBJECTIVE: Bone shape and bone marrow lesions (BMLs) represent different features of Magnetic resonance imaging (MRI)-detected subchondral pathology in osteoarthritis (OA). The aim of this study was to determine how these features are related and how they change in OA progression. METHODS: 600 participants from the Osteoarthritis Initiative (OAI) FNIH Biomarkers Initiative were included, having Kellgren-Lawrence grade 1-3, at baseline and MRI data at baseline and 24 months. The associations between 3D quantitative bone shape vectors and presence of (MRI Osteoarthritis Knee Score) MOAKS semi-quantitative BMLs (total BML size ≥1) were analysed for femurs and tibias using linear regression. Responsiveness over 24 months was calculated for both features in four pre-defined progression groups and reported as standardised response means (SRMs). Multilevel models investigated the longitudinal relationship between change in BML size and change in bone shape. RESULTS: Mean age was 61.5, 59% female and mean body mass index (BMI) 30.7. Correlation between baseline femur vector and BML was r = 0.28, P < 0.001. The presence of BMLs was associated with higher bone shape vector; coefficient (95% CI) 0.75 (0.54, 0.96) and 0.57 (0.38, 0.77) for femur and tibia respectively, both P < 0.001. After covariate adjustment, only the femur remained significant [coefficient 0.49, (95% CI 0.30, 0.68)]. Longitudinally bone vector demonstrated more responsiveness to change than BMLs (SRM 0.89 vs 0.13) while multilevel models revealed that increase in BML size was related to a more positive bone shape vector (representing worsening OA). CONCLUSION: There is a relationship between bone shape and BMLs, with prevalence of BMLs associated with increasing OA bone shape. Bone shape demonstrated greater responsiveness than semi-quantitative BMLs.


Asunto(s)
Médula Ósea/patología , Fémur/patología , Imagenología Tridimensional , Articulación de la Rodilla/patología , Imagen por Resonancia Magnética/métodos , Osteoartritis de la Rodilla/diagnóstico , Tibia/patología , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Índice de Severidad de la Enfermedad
5.
Osteoarthritis Cartilage ; 26(1): 62-71, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-29054695

RESUMEN

OBJECTIVES: Meniscal pathology is integral to knee osteoarthritis (OA) and its progression; it provides a progression biomarker and a potential treatment target. Magnetic resonance imaging (MRI) demonstrates large heterogeneity in meniscal damage; this structural complexity means measurement is difficult. The aim of this study was to apply novel 3D image analysis to determine which meniscal pathologies demonstrated most change during OA progression. METHODS: Knee images were selected from the progression cohort of the Osteoarthritis Initiative choosing participants with risk factors for medial OA progression. Medial and lateral menisci were manually segmented then analysed using a statistical shape model of the tibia as a reference surface. Responsiveness was assessed at 1 year using standardised response means (SRMs) for four constructs: meniscal volume, extrusion volume, thickness and tibial coverage; anatomical sub-regions of these constructs were also explored. RESULTS: Paired images from 86 participants (median age 61.5, 49% female, 56% obese) were included. Reliability of the novel meniscal measurements was very good intraclass correlation coefficients (ICCs all > 0.98). Meniscal volume and extrusion demonstrated no significant change. Moderate responsiveness was observed for medial meniscus thickness (SRM -0.35) and medial tibial coverage (SRM -0.36). No substantial change was seen for the lateral meniscus measures. Sub-region analysis did not improve responsiveness; while greater change was seen in the posterior medial compartment, it was associated with increased variance of the change. CONCLUSIONS: The location of meniscal damage was consistently in the posterior medial region, and two measurements (thickness and tibial coverage) were most responsive. Meniscal measures should add to discriminatory power in OA progression assessment.


Asunto(s)
Meniscos Tibiales/patología , Osteoartritis de la Rodilla/patología , Anciano , Índice de Masa Corporal , Enfermedades de los Cartílagos/patología , Progresión de la Enfermedad , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Tamaño de los Órganos , Reproducibilidad de los Resultados , Estudios Retrospectivos , Factores Sexuales
6.
Eur Radiol ; 27(2): 723-731, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-27277260

RESUMEN

OBJECTIVES: To determine if quantitative and qualitative shear wave elastography have roles in evaluating musculoskeletal masses. METHODS: 105 consecutive patients, prospectively referred for biopsy within a specialist sarcoma centre, underwent B-mode, quantitative (m/s) and qualitative (colour map) shear wave elastography. Reference was histology from subsequent biopsy or excision where possible. Statistical modelling was performed to test elastography data and/or B-mode imaging in predicting malignancy. RESULTS: Of 105 masses, 39 were malignant and 6 had no histology but benign characteristics at 12 months. Radiologist agreement for B-mode and elastography was moderate to excellent Kw 0.52-0.64; PABAKw 0.85-0.90). B-Mode imaging had 78.8% specificity, 76.9% sensitivity for malignancy. Quantitatively, adjusting for age, B-mode and lesion volume there was no statistically significant association between longitudinal velocity and malignancy (OR [95% CI] 0.40[0.10, 1.60], p=0.193), but some evidence that higher transverse velocity was associated with decreased odds of malignancy (0.28[0.06, 1.28], p=0.101). Qualitatively malignant masses tended to be towards the blue spectrum (lower velocities); 39.5% (17/43) of predominantly blue masses were malignant, compared to 14.3% (1/7) of red lesions. CONCLUSIONS: Quantitatively and qualitatively there is no statistically significant association between shear wave velocity and malignancy. There is no clear additional role to B-mode imaging currently. KEY POINTS: • Correlation between shear wave velocity and soft tissue malignancy was statistically insignificant • B-mode ultrasound is 76.9 % sensitive and 78.8 % specific • Statistical models show elastography does not significantly add to lesion assessment.


Asunto(s)
Diagnóstico por Imagen de Elasticidad/métodos , Sarcoma/diagnóstico por imagen , Neoplasias de los Tejidos Blandos/diagnóstico por imagen , Ultrasonografía Doppler en Color/métodos , Adulto , Anciano , Anciano de 80 o más Años , Biopsia , Femenino , Tumor Glómico/diagnóstico por imagen , Humanos , Liposarcoma/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Peso Molecular , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Ultrasonografía , Adulto Joven
7.
Ann Rheum Dis ; 74(9): 1659-66, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24728331

RESUMEN

OBJECTIVES: To monitor progression to inflammatory arthritis (IA) in individuals with non-specific musculoskeletal (MSK) symptoms and positive anticyclic citrullinated peptide (anti-CCP) antibodies. To develop a pragmatic model to predict development of IA in this patient group. METHODS: In this prospective observational cohort, patients with new non-specific MSK symptoms and positive anti-CCP were recruited from regional primary care and secondary care referrals. Clinical, imaging and serological parameters were assessed at baseline. Cox regression analysis was performed to identify predictors of progression to IA and develop a risk score to stratify patients at presentation. FINDINGS: 100 consecutive patients (73 women, mean age 51 years) were followed up for median 19.8 months (range 0.1-69.0); 50 developed IA after a median 7.9 months (range 0.1-52.4), 34 within 12 months. The majority (43/50) fulfilled the 2010 American College of Rheumatology/European League Against Rheumatism criteria for rheumatoid arthritis. A model for progression to IA was devised using four variables: tenderness of hand or foot joints, early morning stiffness ≥30 min, high-positive autoantibodies, and positive ultrasonographic power Doppler signal. None of the five individuals at low risk (score 0) progressed to IA, compared with 31% of 29 at moderate risk (1-2) and 62% of 66 at high risk (≥3). Adding shared epitope increased the number at low risk (score 0-1; 0/11 progressed). CONCLUSIONS: In patients presenting with non-specific MSK symptoms and anti-CCP, the risk of progression to IA could be quantified using data available in clinical practice. The proposed risk score may be used to stratify patients for early therapeutic intervention. TRIAL REGISTRATION NUMBER: NCT02012764 at ClinicalTrials.gov.


Asunto(s)
Artritis Reumatoide/inmunología , Autoanticuerpos/inmunología , Péptidos Cíclicos/inmunología , Adulto , Anciano , Estudios de Cohortes , Técnicas de Apoyo para la Decisión , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Adulto Joven
8.
Osteoarthritis Cartilage ; 23(11): 1870-8, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26162804

RESUMEN

OBJECTIVES: Immune age-related abnormalities may synergise with osteoarthritis (OA) pathology. We explored whether abnormalities in the blood immune cell composition are present in OA, beyond defects typically associated with ageing. DESIGN: Blood was collected from 121 healthy controls (HC) and 114 OA patients. Synovial biopsies were obtained from another 52 OA patients. Flow cytometry was used to establish the frequencies of lineage subsets, naïve, memory and regulatory T and B-cells, cells with an abnormal phenotype related to inflammation (IRC) and memory-like CD8(+) T-cells. Multivariate analysis of covariance (MANCOVA) was used to determine whether the relative subset frequencies differed between HC and OA, controlling for age. RESULTS: Expected histology and T/B-cell infiltration were observed. Following age adjusted analysis, we confirmed the lack of age association in HC for CD4(+), B, NK and NKT cells but a negative trend for CD8(+) T-cells. In OA, CD4(+) T-cell and B-cell frequency were lower compared to HC while CD8(+) T-cell frequencies were higher. CD8(+) memory-like cells were more likely to be found in OA (odds ratio = 15). Increased CD8(+) IRC frequencies were also present in OA. The relationship between age and CD4(+) or CD8(+) naïve T-cells in HC were changed in OA while the age relationships with memory cells were lost. The increase in CD4(+) Treg with age was also lost in OA. B-cells showed limited evidence of disturbance. CONCLUSIONS: Immune dysfunction may be present in OA beyond what appears related to ageing; this requires further investigation.


Asunto(s)
Inmunidad Celular , Osteoartritis/inmunología , Membrana Sinovial/inmunología , Linfocitos T/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Envejecimiento/inmunología , Envejecimiento/patología , Biopsia , Recuento de Células Sanguíneas , Femenino , Citometría de Flujo , Humanos , Masculino , Persona de Mediana Edad , Osteoartritis/patología , Membrana Sinovial/patología , Linfocitos T/patología , Adulto Joven
9.
Reumatismo ; 67(3): 91-6, 2015 Dec 30.
Artículo en Inglés | MEDLINE | ID: mdl-26876187

RESUMEN

Biomechanical factors including occupational joint physical stressing and joint injury have been linked to spondyloarthritis. We explored such factors in ankylosing spondylitis (AS). A retrospective, online survey was developed alongside the UK National Ankylosing Spondylitis Society (NASS). Questions on early entheseal symptoms, potential precipitating trauma, sporting activity, and physiotherapy were asked. A total of 1026 patients responded with 44% recalling an instance of injury or trauma as a potential trigger for their AS. After symptom onset, 55% modified sporting activities and 28% reported that the initial AS recommended exercises exacerbated symptoms. Patients report physical trauma, exercise and physiotherapy as potential triggers for AS symptoms. These findings further support the experimental evidence for the role of biomechanical factors in disease.


Asunto(s)
Ejercicio Físico , Espondilitis Anquilosante/etiología , Heridas y Lesiones/complicaciones , Adulto , Fenómenos Biomecánicos , Femenino , Humanos , Masculino , Estudios Retrospectivos , Factores de Riesgo , Encuestas y Cuestionarios , Reino Unido
10.
Ann Rheum Dis ; 73(6): 1027-36, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24618266

RESUMEN

OBJECTIVE: To compare the efficacy of etanercept (ETN) and methotrexate (MTX) versus MTX monotherapy for remission induction in patients with early inflammatory arthritis. METHODS: In a 78-week multicentre randomised placebo-controlled superiority trial, 110 DMARD-naïve patients with early clinical synovitis (≥1 tender and swollen joint, and within 3 months of diagnosis) and either rheumatoid factor, anticitrullinated protein antibodies or shared epitope positive were randomised 1:1 to receive MTX+ETN or MTX+placebo (PBO) for 52 weeks. Injections (ETN or PBO) were stopped in all patients at week 52. In those with no tender or swollen joints (NTSJ) for >26 weeks, injections were stopped early. If patients had NTSJ >12 weeks after stopping the injections, MTX was weaned. The primary endpoint was NTSJ at week 52. RESULTS: No statistically significant difference was seen for the primary endpoint (NTSJ at week 52 (32.5% vs 28.1% [adjusted OR 1.32 (0.56 to 3.09), p=0.522]) in the MTX+ETN and MTX+PBO groups, respectively). The secondary endpoints did not differ between groups at week 52 or 78. Exploratory analyses showed a higher proportions of patients with DAS28-CRP<2.6 in the MTX+ETN group at week 2 (38.5% vs 9.2%, adjusted OR 8.87 (2.53 to 31.17), p=0.001) and week 12 (65.1% vs 43.8%, adjusted OR 2.49 (1.12 to 5.54), p=0.026). CONCLUSIONS: In this group of patients with early inflammatory arthritis, almost a third had no tender, swollen joints after 1 year. MTX+ETN was not superior to MTX monotherapy in achieving this outcome. Clinical responses, however, including DAS28-CRP<2.6, were achieved earlier with MTX+ETN combination therapy. TRIAL REGISTRATION NUMBER: The EMPIRE trial is registered on the following trial registries: Eudract-2005-005467-29; ISRCTN 55428162 (http://www.controlled-trials.com/ISRCTN55428162/EMPIRE). The full trial protocol can be obtained from the corresponding author.


Asunto(s)
Antirreumáticos/uso terapéutico , Artritis/tratamiento farmacológico , Inmunoglobulina G/uso terapéutico , Metotrexato/uso terapéutico , Receptores del Factor de Necrosis Tumoral/uso terapéutico , Sinovitis/tratamiento farmacológico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Artritis/inmunología , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/inmunología , Autoanticuerpos/inmunología , Método Doble Ciego , Quimioterapia Combinada/métodos , Intervención Médica Temprana/métodos , Etanercept , Femenino , Humanos , Quimioterapia de Inducción/métodos , Masculino , Persona de Mediana Edad , Inducción de Remisión/métodos , Factor Reumatoide/inmunología , Resultado del Tratamiento , Adulto Joven
11.
Ann Rheum Dis ; 73(1): 75-85, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23912798

RESUMEN

OBJECTIVES: In disease modifying antirheumatic drug (DMARD)-naive early rheumatoid arthritis (RA), to compare the efficacy of methotrexate (MTX) and infliximab (IFX) with MTX and intravenous corticosteroid for remission induction. METHODS: In a 78-week multicentre randomised controlled trial, double-blinded to week 26, 112 treatment-naive RA patients (1987 American College of Rheumatology classification criteria) with disease activity score 44 (DAS44)>2.4 were randomised to MTX + IFX or MTX + single dose intravenous methylprednisolone 250 mg. A treat-to-target approach was used with treatment escalation if DAS44>2.4. In the IFX group, IFX was discontinued for sustained remission (DAS44<1.6 for 6 months). The primary outcome was change in modified total Sharp-van der Heijde score (mTSS) at week 50. RESULTS: The mean changes in mTSS score at week 50 in the IFX and intravenous steroid groups were 1.20 units and 2.81 units, respectively (adjusted difference (95% CI) -1.45 (-3.35 to 0.45); p=0.132). Radiographic non-progression (mTSS<2.0) occurred in 81% vs 71% (OR 1.77 (0.56 to 5.61); p=0.328). DAS44 remission was achieved at week 50 in 49% and 36% (OR 2.13 (0.91 to 5.00); p=0.082), and at week 78 in 48% and 50% (OR 1.12 (0.47 to 2.68); p=0.792). Exploratory analyses suggested higher DAS28 remission at week 6 and less ultrasound synovitis at week 50 in the IFX group. Of the IFX group, 25% (14/55) achieved sustained remission and stopped IFX. No substantive differences in adverse events were seen. CONCLUSIONS: In DMARD-naive early RA patients, initial therapy with MTX+high-dose intravenous steroid resulted in good disease control with little structural damage. MTX+IFX was not statistically superior to MTX+intravenous steroid when combined with a treat-to-target approach.


Asunto(s)
Anticuerpos Monoclonales/administración & dosificación , Antirreumáticos/administración & dosificación , Artritis Reumatoide/tratamiento farmacológico , Esteroides/administración & dosificación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales/efectos adversos , Antirreumáticos/efectos adversos , Artritis Reumatoide/diagnóstico , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Humanos , Infliximab , Inyecciones Intravenosas , Masculino , Persona de Mediana Edad , Inducción de Remisión , Resultado del Tratamiento , Adulto Joven
12.
Osteoarthritis Cartilage ; 22(10): 1614-8, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25278070

RESUMEN

OBJECTIVE: Sensitive biomarkers are needed to understand synovial response to therapy in osteoarthritis (OA). Dynamic, contrast-enhanced magnetic resonance imaging (DCE MRI) provides quantitative, novel measures of synovial inflammation. This exploratory study examined DCE-assessed synovial response to intra-articular corticosteroid (IACS). METHODS: People with ACR clinical criteria OA knee underwent 3 T MRI pre- and 2 weeks post-IACS. Five MRI variables were assessed blindly: total synovial volume (semi-automated computer program), early enhancement rate (EER) and late enhancement ratio of the entire knee, synovial volume × late enhancement and a semi-quantitative (SQ) score (six sites scored 0-3). Clinical symptoms were assessed using pain visual analogue score (VAS) and WOMAC. RESULTS: 13 participants (5 male, mean age 63, mean pain VAS 66 mm mean body mass index (BMI) 31.3 kg/m(2)) were included. The majority of MRIs demonstrated no change in SQ score although the DCE variables changed to some extent in all. There was generally a reduction in synovial volume ((Wilcoxon test) median (interquartile range (IQR)) reduction 14 cm(3) (-1, 29)), EER (0.2% (-0.3, 0.6)) and late enhancement ratio (8% (-0.5, 41)). Synovial volume × late enhancement ratio demonstrated a substantive reduction (2250 (-930, 5630)) as well as the largest effect size, r = 0.45. There was a median 26% reduction in EER in participants with good symptomatic response to IACS, contrasting with a 23% increase in those who responded poorly. CONCLUSIONS: DCE MRI may be more sensitive than a SQ score at detecting post-therapy synovial changes. The association between EER and symptomatic response to IACS may reflect a closer relation of this biomarker to synovial inflammation than with volumetric assessment.


Asunto(s)
Corticoesteroides/uso terapéutico , Artralgia/tratamiento farmacológico , Articulación de la Rodilla/patología , Osteoartritis de la Rodilla/patología , Sinovitis/patología , Anciano , Artralgia/etiología , Medios de Contraste , Femenino , Humanos , Inyecciones Intraarticulares , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Osteoartritis de la Rodilla/complicaciones , Osteoartritis de la Rodilla/tratamiento farmacológico , Sinovitis/tratamiento farmacológico , Sinovitis/etiología , Resultado del Tratamiento
13.
Osteoarthritis Cartilage ; 22(10): 1703-9, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25278079

RESUMEN

BACKGROUND: Radiographic measures of osteoarthritis (OA) are based upon two dimensional projection images. Active appearance modelling (AAM) of knee magnetic resonance imaging (MRI) enables accurate, 3D quantification of joint structures in large cohorts. This cross-sectional study explored the relationship between clinical characteristics, radiographic measures of OA and 3D bone area (tAB). METHODS: Clinical data and baseline paired radiographic and MRI data, from the medial compartment of one knee of 2588 participants were obtained from the NIH Osteoarthritis Initiative (OAI). The medial femur (MF) and tibia (MT) tAB were calculated using AAM. 'OA-attributable' tAB (OA-tAB) was calculated using data from regression models of tAB of knees without OA. Associations between OA-tAB and radiographic measures of OA were investigated using linear regression. RESULTS: In univariable analyses, height, weight, and age in female knees without OA explained 43.1%, 32.1% and 0.1% of the MF tAB variance individually and 54.4% when included simultaneously in a multivariable model. Joint space width (JSW), osteophytes and sclerosis explained just 5.3%, 14.9% and 10.1% of the variance of MF OA-tAB individually and 17.4% when combined. Kellgren Lawrence (KL) grade explained approximately 20% of MF OA-tAB individually. Similar results were seen for MT OA-tAB. CONCLUSION: Height explained the majority of variance in tAB, confirming an allometric relationship between body and joint size. Radiographic measures of OA, derived from a single radiographic projection, accounted for only a small amount of variation in 3D knee OA-tAB. The additional structural information provided by 3D bone area may explain the lack of a substantive relationship with these radiographic OA measures.


Asunto(s)
Fémur/patología , Osteoartritis de la Rodilla/patología , Tibia/patología , Factores de Edad , Anciano , Estatura , Peso Corporal , Femenino , Fémur/diagnóstico por imagen , Humanos , Imagenología Tridimensional , Modelos Lineales , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Modelos Teóricos , Obesidad/complicaciones , Tamaño de los Órganos , Osteoartritis de la Rodilla/complicaciones , Osteoartritis de la Rodilla/diagnóstico por imagen , Osteofito/diagnóstico por imagen , Osteofito/etiología , Osteofito/patología , Radiografía , Tibia/diagnóstico por imagen
14.
Eur J Endocrinol ; 186(4): 441-455, 2022 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-35113805

RESUMEN

BACKGROUND: Chronic wounds (e.g. diabetic foot ulcers) reduce the quality of life, yet treatments remain limited. Glucocorticoids (activated by the enzyme 11ß-hydroxysteroid dehydrogenase type 1, 11ß-HSD1) impair wound healing. OBJECTIVES: Efficacy, safety, and feasibility of 11ß-HSD1 inhibition for skin function and wound healing. DESIGN: Investigator-initiated, double-blind, randomized, placebo-controlled, parallel-group phase 2b pilot trial. METHODS: Single-center secondary care setting. Adults with type 2 diabetes mellitus without foot ulcers were administered 400 mg oral 11ß-HSD1 inhibitor AZD4017 (n = 14) or placebo (n = 14) bi-daily for 35 days. Participants underwent 3-mm full-thickness punch skin biopsies at baseline and on day 28; wound healing was monitored after 2 and 7 days. Computer-generated 1:1 randomization was pharmacy-administered. Analysis was descriptive and focused on CI estimation. Of the 36 participants screened, 28 were randomized. RESULTS: Exploratory proof-of-concept efficacy analysis suggested AZD4017 did not inhibit 24-h ex vivoskin 11ß-HSD1 activity (primary outcome; difference in percentage conversion per 24 h 1.1% (90% CI: -3.4 to 5.5) but reduced systemic 11ß-HSD1 activity by 87% (69-104%). Wound diameter was 34% (7-63%) smaller with AZD4017 at day 2, and 48% (12-85%) smaller after repeat wounding at day 30. AZD4017 improved epidermal integrity but modestly impaired barrier function. Minimal adverse events were comparable to placebo. Recruitment rate, retention, and data completeness were 2.9/month, 27/28, and 95.3%, respectively. CONCLUSION: A phase 2 trial is feasible, and preliminary proof-of-concept data suggests AZD4017 warrants further investigation in conditions of delayed healing, for example in diabetic foot ulcers. SIGNIFICANCE STATEMENT: Stress hormone activation by the enzyme 11ß-HSD type 1 impairs skin function (e.g. integrity) and delays wound healing in animal models of diabetes, but effects in human skin were previously unknown. Skin function was evaluated in response to treatment with a 11ß-HSD type 1 inhibitor (AZD4017), or placebo, in people with type 2 diabetes. Importantly, AZD4017 was safe and well tolerated. This first-in-human randomized, controlled, clinical trial found novel evidence that 11ß-HSD type 1 regulates skin function in humans, including improved wound healing, epidermal integrity, and increased water loss. Results warrant further studies in conditions of impaired wound healing, for example, diabetic foot ulcers to evaluate 11ß-HSD type 1 as a novel therapeutic target forchronic wounds.


Asunto(s)
11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 1/antagonistas & inhibidores , Diabetes Mellitus Tipo 2/complicaciones , Pie Diabético/tratamiento farmacológico , Niacinamida/análogos & derivados , Piperidinas/uso terapéutico , Piel/efectos de los fármacos , Cicatrización de Heridas/efectos de los fármacos , Adulto , Anciano , Anciano de 80 o más Años , Pie Diabético/patología , Método Doble Ciego , Epidermis/efectos de los fármacos , Epidermis/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Niacinamida/uso terapéutico , Proyectos Piloto , Calidad de Vida , Piel/patología , Piel/fisiopatología , Resultado del Tratamiento
15.
Ann Rheum Dis ; 70(2): 331-3, 2011 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-20980286

RESUMEN

OBJECTIVES: In rheumatoid arthritis, high levels of the cartilage turnover biomarker C-terminal cross-linking telopeptide of type II collagen (CTX-II) predict an increased risk of radiological progression. In very early inflammatory arthritis erosions are uncommon, therefore CTX-II requires validation against early markers of inflammatory arthritis such as power Doppler ultrasound (PDUS) synovitis and bone mineral density (BMD) loss. METHODS: In 50 subjects with 12 weeks or less of inflammatory hand symptoms, urinary CTX-II and PDUS were performed at baseline and hand BMD at baseline and 12 months. CTX-II data were log transformed to a normal distribution. Associations between variables were examined using Pearson's r/Spearman's ρ correlations. RESULTS: The mean 12- month change in BMD was -0.0068 g/cm² and the geometric mean for baseline CTX-II/creatinine was 245.89 ng/mmol. Log-transformed baseline CTX-II showed a substantive negative association with change in average BMD over 12 months, controlling for baseline BMD and erythrocyte sedimentation rate (r=-0.359, p=0.044). The median total PDUS score was 3.0 and baseline CTX-II was significantly associated with baseline total PDUS (Spearman's ρ=0.482, p=0.002). CONCLUSION: Urinary CTX-II correlates with PDUS synovitis and hand BMD reduction very early in the course of inflammatory arthritis, suggesting that CTX-II has potential as a biomarker in very early inflammatory arthritis.


Asunto(s)
Artritis Reumatoide/diagnóstico , Colágeno Tipo II/orina , Fragmentos de Péptidos/orina , Sinovitis/diagnóstico , Absorciometría de Fotón , Adulto , Artritis Reumatoide/complicaciones , Artritis Reumatoide/fisiopatología , Biomarcadores/orina , Densidad Ósea/fisiología , Progresión de la Enfermedad , Diagnóstico Precoz , Femenino , Estudios de Seguimiento , Articulaciones de la Mano/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Sinovitis/complicaciones , Sinovitis/fisiopatología , Sinovitis/orina
16.
Ann Rheum Dis ; 69(5): 891-4, 2010 May.
Artículo en Inglés | MEDLINE | ID: mdl-19666937

RESUMEN

BACKGROUND: Fatty changes at vertebral corners have been reported on MRI in ankylosing spondylitis but the distribution or specificity of these lesions to early axial spondyloarthropathy (axial-SpA) has not been determined. OBJECTIVE: To assess the diagnostic utility of fatty Romanus lesions (FRLs) for axial-SpA in a population with chronic back pain. METHODS: Axial-skeleton TI SE and fat-suppressed MRI were performed on 174 patients with back pain and 11 controls. MRI lesions including FRLs were scored blind. An imaging diagnosis was given on MRI findings alone and compared with the 'gold standard' treating doctor's diagnosis. RESULTS: Twenty-nine patients had FRLs: 31% (20/64) of patients with spondyloarthropathy, 13% (6/45) with degenerative arthritis, 4% (2/45) with spinal malignancy, 5% (1/20) with 'other' diagnoses; none of 11 normal subjects had FRLs. The majority of the FRLs in SpA 60% (135/226) were present in the thoracic spine. The diagnostic utility of FRLs for SpA (likelihood ratio (LR) = 4.7) was significantly (p<0.05) greater than for other diagnoses and increased further (LR = 12.6, p<0.05) when more than five FRLs were present. Of note 5/20 (25%) patients with SpA with FRLs had no diagnostic bone-oedema lesions on fat-suppressed MRI, suggesting that FRLs may be useful diagnostically in axial-SpA. CONCLUSION: This study defines the FRL as a diagnostic imaging feature of axial-SpA, which may be useful where inflammatory changes are absent on fat-suppression MRI and where radiography is normal.


Asunto(s)
Tejido Adiposo/patología , Vértebra Cervical Axis/patología , Espondiloartropatías/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Dolor de Espalda/etiología , Humanos , Vértebras Lumbares/patología , Imagen por Resonancia Magnética/métodos , Persona de Mediana Edad , Osteítis/diagnóstico , Espondiloartropatías/complicaciones , Vértebras Torácicas/patología , Adulto Joven
17.
Ann Rheum Dis ; 69(2): 417-9, 2010 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-19359260

RESUMEN

OBJECTIVES: The aim of this study was to assess the value of power Doppler ultrasound (PDUS) in combination with routine management in a cohort of patients with very early inflammatory arthritis (IA). METHODS: 50 patients with < or =12 weeks of inflammatory symptoms with or without signs had clinical, laboratory and imaging assessments. Diagnosis was recorded at 12 months. Assuming a 15% pre-test probability of IA, post-test probabilities for various assessments were calculated and used to develop a diagnostic algorithm. RESULTS: All patients positive for rheumatoid factor (RF) and/or cyclic citrullinated peptide (CCP) developed persistent IA, so the added value of PDUS was assessed in the seronegative (RF and CCP negative) group. The probability of IA in a seronegative patient was 6%. The addition of clinical and radiographic features raised the probability of IA to 30% and, with certain ultrasound features, this rose to 94%. CONCLUSIONS: In seronegative patients with early IA, combining PDUS with routine assessment can have a major impact on the certainty of diagnosis.


Asunto(s)
Algoritmos , Artritis Reumatoide/diagnóstico por imagen , Adulto , Anciano , Anciano de 80 o más Años , Artritis Reumatoide/diagnóstico , Autoanticuerpos/sangre , Biomarcadores/sangre , Árboles de Decisión , Diagnóstico Precoz , Femenino , Articulaciones de la Mano/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Péptidos Cíclicos/inmunología , Pronóstico , Factor Reumatoide/sangre , Sensibilidad y Especificidad , Ultrasonografía Doppler/métodos , Adulto Joven
18.
Ann Rheum Dis ; 69(6): 976-86, 2010 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-20447957

RESUMEN

OBJECTIVES: To review the evidence for the efficacy and safety of biological agents in patients with rheumatoid arthritis (RA) to provide data to develop treatment recommendations by the European League Against Rheumatism (EULAR) Task Force. METHODS: Medline, Embase and Cochrane databases were searched for relevant articles on infliximab (IFX), etanercept (ETN), adalimumab (ADA), certolizumab-pegol (CZP), golimumab (GLM), anakinra (ANA), abatacept (ABT), rituximab (RTX) and tocilizumab (TCZ) published between 1962 and February 2009; published abstracts from the 2007-2008 American College of Rheumatology (ACR) and EULAR conference were obtained. RESULTS: 87 articles and 40 abstracts were identified. In methotrexate (MTX) naïve patients, biological therapy with IFX, ETN, ADA, GLM or ABT has been shown to improve clinical outcomes (level of evidence 1B). In MTX/other synthetic disease-modifying antirheumatic drug (DMARD) failures all nine biological agents confer benefit (1B), with lower efficacy noted for ANA. RTX, ABT, TCZ and GLM demonstrate efficacy in tumour necrosis factor inhibitor (TNFi) failures (1B). Less evidence exists for switching between IFX, ETN and ADA (3B). Biological and MTX combination therapy is more efficacious than a biological agent alone (1B). A safety review shows no increased malignancy risk compared with conventional DMARDs (3B). TNFi are generally associated with an increased risk of serious bacterial infection, particularly within the first 6 months of treatment initiation; increased tuberculosis (TB) rates with TNFi are highest with the monoclonal antibodies (3B). CONCLUSIONS: There is good evidence for the efficacy of biological agents in patients with RA. Safety data confirm an increased risk of bacterial infection and TB with TNFi compared with conventional DMARDs.


Asunto(s)
Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Antirreumáticos/efectos adversos , Quimioterapia Combinada , Medicina Basada en la Evidencia/métodos , Humanos , Metotrexato/uso terapéutico , Infecciones Oportunistas/inducido químicamente , Guías de Práctica Clínica como Asunto , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores
19.
J Fish Biol ; 76(10): 2287-98, 2010 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-20557593

RESUMEN

In the presence of a vertical thermal gradient, juvenile three-spined sticklebacks Gasterosteus aculeatus and minnows Phoxinus phoxinus positioned themselves higher in the water column compared with adult conspecifics. This result was consistent regardless of whether age cohorts were tested separately or together. Furthermore, juveniles but not adult fishes positioned themselves higher in water column in the presence of a thermal gradient compared with those in the absence of a thermal gradient. Juvenile G. aculeatus and adult fish of both species did opt to position themselves higher in the water column in the hours immediately following a feeding event relative to their positions in the same gradient when they had not fed.


Asunto(s)
Regulación de la Temperatura Corporal , Smegmamorpha/fisiología , Animales , Conducta Alimentaria , Agua Dulce
20.
Int J Cardiovasc Imaging ; 36(3): 491-501, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32036488

RESUMEN

The accelerated risk of cardiovascular disease (CVD) in Rheumatoid Arthritis (RA) requires further study of the underlying pathophysiology and determination of the at-risk RA phenotype. Our objectives were to describe the cardiac structure and function and arterial stiffness, and association with disease phenotype in patients with established) RA, in comparison to healthy controls, as measured by cardiovascular magnetic resonance imaging (CMR). 76 patients with established RA and no history of CVD/diabetes mellitus were assessed for RA and cardiovascular profile and underwent a non-contrast 3T-CMR, and compared to 26 healthy controls. A univariable analysis and multivariable linear regression model determined associations between baseline variables and CMR-measures. Ten-year cardiovascular risk scores were increased in RA compared with controls. Adjusting for age, sex and traditional cardiovascular risk factors, patients with RA had reduced left ventricular ejection fraction (mean difference - 2.86% (- 5.17, - 0.55) p = 0.016), reduced absolute values of mid systolic strain rate (p < 0.001) and lower late/active diastolic strain rate (p < 0.001) compared to controls. There was evidence of reduced LV mass index (LVMI) (- 4.56 g/m2 (- 8.92, - 0.20), p = 0.041). CMR-measures predominantly associated with traditional cardiovascular risk factors; male sex and systolic blood pressure independently with increasing LVMI. Patients with established RA and no history of CVD have evidence of reduced LV systolic function and LVMI after adjustment for traditional cardiovascular risk factors; the latter suggesting cardiac pathology other than atherosclerosis in RA. Traditional cardiovascular risk factors, rather than RA disease phenotype, appear to be key determinants of subclinical CVD in RA potentially warranting more effective cardiovascular risk reduction programs.


Asunto(s)
Artritis Reumatoide/complicaciones , Imagen por Resonancia Cinemagnética , Disfunción Ventricular Izquierda/diagnóstico por imagen , Función Ventricular Izquierda , Remodelación Ventricular , Adulto , Anciano , Anciano de 80 o más Años , Artritis Reumatoide/diagnóstico , Estudios de Casos y Controles , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fenotipo , Valor Predictivo de las Pruebas , Medición de Riesgo , Factores de Riesgo , Sístole , Rigidez Vascular , Disfunción Ventricular Izquierda/etiología , Disfunción Ventricular Izquierda/fisiopatología
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