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1.
Artigo em Inglês | MEDLINE | ID: mdl-31580450

RESUMO

OBJECTIVE: To examine whether the presence of bulge sign or patellar tap was associated with frequent knee pain, progression of radiographic OA (ROA) and total knee replacement (TKR). METHODS: This study included 4344 Osteoarthritis Initiative participants examined at baseline for bulge sign and/or patellar tap. The clinical signs were categorized as no (none at baseline and 2 years), resolved (present at baseline only), developed (present at 2 years only) and persistent (present at both time points). Frequent knee pain and progression of ROA over 4 years and TKR over 6 years were assessed. Binary logistic regression was used to examine the associations. RESULTS: A total of 12.7% of participants had bulge sign only, 2.0% had patellar tap only and 3.3% had both. A positive baseline bulge sign was associated with an increased risk of frequent knee pain [OR 1.31 (95% CI 1.04, 1.64), P = 0.02] and TKR [OR 1.47 (95% CI 1.06, 2.05), P = 0.02]. Developed bulge sign was associated with an increased risk of frequent knee pain [OR 1.75 (95% CI 1.34, 2.29), P < 0.001] and progressive ROA [OR 1.67 (95% CI 1.11, 2.51), P = 0.01]. Persistent bulge sign was associated with an increased risk of frequent knee pain [OR 1.60 (95% CI 1.09, 2.35), P = 0.02], progressive ROA [OR 1.84 (95% CI 1.01, 3.33), P = 0.045] and TKR [OR 2.13 (95% CI 1.23, 3.68), P = 0.007]. Patellar tap was not examined for its association with joint outcomes due to its low prevalence. CONCLUSION: The presence of bulge sign identifies individuals at increased risk of frequent knee pain, progression of ROA and TKR. This provides clinicians with a quick, simple, inexpensive method for identifying those at higher risk of progressive knee OA who should be targeted for therapy.

2.
Clin Rheumatol ; 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31478110

RESUMO

INTRODUCTION/OBJECTIVE: Knee alignment and anterior cruciate ligament (ACL) injury are risk factors for knee osteoarthritis (OA). The objective was to examine interactions between knee alignment and ACL status on cartilage volume loss in participants with or at risk of knee OA. METHOD: Participants were from the Osteoarthritis Initiative, a longitudinal cohort study. Data were from baseline and 24- and 72-month follow-up visits. Participants with knee OA (progression subcohort) or at risk of knee OA (incidence subcohort) that had partial or full ACL tears (OA-ACL group; n=66) or an intact ACL (OA-only group, n=367) were selected. Femur-tibia angles from radiographs quantified knee alignment. Changes in tibial and femoral cartilage volumes were measured using magnetic resonance imaging. Hierarchical linear models examined if knee alignment, presence of ACL, and their interaction were related to cartilage volume loss after accounting for other variables. RESULTS: Interactions between alignment and ACL status were significantly related to cartilage volume loss in the lateral plateau (ß=-20.19, 95% confidence interval [CI]=-34.65 to -5.73) and lateral condyle (ß=-23.64, 95%CI=-43.06 to -4.23). Valgus alignment was related to lateral compartment cartilage loss in the OA-ACL group, but not in the OA-only group. Varus alignment was related to cartilage loss in the medial plateau (ß=7.49, 95%CI=0.17 to 14.80) and medial condyle (ß=19.70, 95%CI=5.96 to 33.44) in both groups. CONCLUSION: The impact of knee alignment on knee OA initiation and progression varies based on ACL status. Initial lateral compartment damage or changes in joint kinematics after ACL rupture might account for these findings. Key Points • The relationship between knee alignment and lateral compartment cartilage loss depended on the status of the anterior cruciate ligament in participants with knee osteoarthritis or at risk for knee osteoarthritis. • Valgus alignment was related to lateral compartment cartilage loss in participants with a deficient anterior cruciate ligament. • Varus alignment was related to medial compartment cartilage loss regardless of the status of the anterior cruciate ligament.

4.
Nutrients ; 11(7)2019 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-31315273

RESUMO

Dietary omega-3 fatty acids (ω3), particularly long-chain ω3 (LCω3), have protective effects against prostate cancer (PCa) in experimental studies. Observational studies are conflicting, possibly because of the biomarker used. This study aimed at evaluating associations between grade reclassification and ω3 levels assessed in prostatic tissue, red blood cells (RBC), and diet. We conducted a validation cross-sectional study nested within a phase II clinical trial. We identified 157 men diagnosed with low-risk PCa who underwent a first active surveillance repeat prostate biopsy session. Fatty acid (FA) intake was assessed using a food frequency questionnaire and their levels measured in prostate tissue and RBC. Associations were evaluated using logistic regression. At first repeat biopsy session, 39 (25%) men had high-grade PCa (grade group ≥2). We found that high LCω3-eicosapentaenoic acid (EPA) level in prostate tissue (odds ratio (OR) 0.25; 95% (confidence interval (CI) 0.08-0.79; p-trend = 0.03) was associated with lower odds of high-grade PCa. Similar results were observed for LCω3 dietary intake (OR 0.30; 95% CI 0.11-0.83; p-trend = 0.02) but no association for RBC. LCω3-EPA levels in the target prostate tissue are inversely associated with high-grade PCa in men with low-risk PCa, supporting that prostate tissue FA, but not RBC FA, is a reliable biomarker of PCa risk.

5.
Neurology ; 93(7): e635-e646, 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31300547

RESUMO

OBJECTIVE: In this study, we compared the effectiveness of teriflunomide (TRF) and dimethyl fumarate (DMF) on both clinical and MRI outcomes in patients followed prospectively in the Observatoire Français de la Sclérose en Plaques. METHODS: A total of 1,770 patients with relapsing-remitting multiple sclerosis (RRMS) (713 on TRF and 1,057 on DMF) with an available baseline brain MRI were included in intention to treat. The 1- and 2-year postinitiation outcomes were relapses, increase of T2 lesions, increase in Expanded Disability Status Scale score, and reason for treatment discontinuation. Propensity scores (inverse probability weighting) and logistic regressions were estimated. RESULTS: The confounder-adjusted proportions of patients were similar in TRF- compared to DMF-treated patients for relapses and disability progression after 1 and 2 years. However, the adjusted proportion of patients with at least one new T2 lesion after 2 years was lower in DMF compared to TRF (60.8% vs 72.2%, odds ratio [OR] 0.60, p < 0.001). Analyses of reasons for treatment withdrawal showed that lack of effectiveness was reported for 8.5% of DMF-treated patients vs 14.5% of TRF-treated patients (OR 0.54, p < 0.001), while adverse events accounted for 16% of TRF-treated patients and 21% of DMF-treated patients after 2 years (OR 1.39, p < 0.001). CONCLUSIONS: After 2 years of treatment, we found similar effectiveness of DMF and TRF in terms of clinical outcomes, but with better MRI-based outcomes for DMF-treated patients, resulting in a lower rate of treatment discontinuation due to lack of effectiveness. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with RRMS, TRF and DMF have similar clinical effectiveness after 2 years of treatment.

6.
Sci Rep ; 9(1): 9648, 2019 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-31273319

RESUMO

To identify serum biomarker(s) for predicting knee cartilage volume loss over time, we studied 139 knee osteoarthritis (OA) patients from a previous 24-month clinical trial cohort. Targeted metabolomic profiling was performed on serum collected at baseline. The pairwise metabolite ratios as proxies for enzymatic reaction were calculated and used in the analysis. Cartilage volume loss between baseline and 24 months was assessed quantitatively by magnetic resonance imaging (MRI). Data revealed an association between the serum ratio of lysophosphatidylcholine 18:2 (lysoPC 18:2) to phosphatidylcholine 44:3 (PC44:3) and the cartilage volume loss in the lateral compartment (ß = -0.21 ± 0.04, p = 8.53*10-7) and with joint degradation markers, COMP (r = 0.32, p = 0.0002) and MMP1 (r = 0.26, p = 0.002). The significance remained after adjustment for age, sex, BMI, diabetes, hypertension, dyslipidemia, and the treatment taken in the original study. As the ratio indicated the over activation of the conversion pathway of PC to lysoPC catalyzed by phospholipase A2 (PLA2), we assessed and found that a specific PLA2, PLA2G5, was significantly increased in human OA cartilage and synovial membrane (85% and 19% respectively, both p < 0.04) compared to controls, and its overexpression correlated with IL-6 (r = 0.63, p = 0.0008). Our data suggest that the serum lysoPC 18:2 to PC44:3 ratio is highly associated with a greater risk of cartilage volume loss of the knee and warrants further investigation in an independent cohort.

7.
BMC Gastroenterol ; 19(1): 103, 2019 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-31234803

RESUMO

BACKGROUND: Biliary mucinous cystic neoplasms are rare cystic lesions of the liver which carry pre-malignant potential. Given the scarcity of reports in the literature, they pose a considerable challenge to clinical management, particularly with regards to accurate pre-operative diagnosis. CASE PRESENTATION: We present the case of a 37-year-old Tunisian woman who presented with subacute right upper quadrant pain and a large multi-loculated cystic lesion, most consistent with a hydatid cyst. She underwent an open right hepatectomy, and pathology surprisingly revealed a biliary mucinous cystadenoma. Herein, we review the current literature on biliary mucinous cystic neoplasms, with a particular emphasis on diagnostic investigations, key radiological features and optimal treatment modalities. CONCLUSION: Biliary mucinous cystic neoplasms require a high index of suspicion and should be managed with complete surgical resection, as conservative techniques are associated with high recurrence rates. Considering the potential for malignant transformation, periodical surveillance imaging is recommended in the post-operative period.

8.
Can J Vet Res ; 83(2): 133-141, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31097875

RESUMO

Osteoarthritis, the leading cause of chronic joint pain, is studied through different animal models, but none of them is ideal in terms of reliability and translational value. In this pilot study of female rats, 3 surgical models of osteoarthritic pain, i.e., destabilization of the medial meniscus (DMM), cranial cruciate ligament transection (CCLT), and the combination of both surgical models (COMBO) and 1 chemical model [intra-articular injection of monosodium iodoacetate (MIA)] were compared for their impact on functional pain outcomes [static weight-bearing (SWB) and punctate tactile paw withdrawal threshold (PWT)] and spinal neuropeptides [substance P (SP), calcitonin gene-related peptide (CGRP), bradykinin (BK), and somatostatin (SST)]. Six rats were assigned to each model group and a sham group. Both the chemical model (MIA) and surgical COMBO model induced functional alterations in SWB and PWT, with the changes being more persistent in the surgical combination group. Both models also produced an increase in levels of pro-nociceptive and anti-nociceptive neuropeptides at different timepoints. Pain comparison with the MIA model showed the advantage of a surgical model, especially the combination of the DMM and CCLT models, whereas each surgical model alone only led to temporary functional alterations and no change in neuropeptidomics.


Assuntos
Modelos Animais de Doenças , Regulação da Expressão Gênica/fisiologia , Neuropeptídeos/metabolismo , Osteoartrite/etiologia , Dor/metabolismo , Animais , Feminino , Injeções Intra-Articulares , Medição da Dor , Projetos Piloto , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Suporte de Carga
9.
Clin Exp Pharmacol Physiol ; 46(8): 723-733, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31046168

RESUMO

The monosodium iodoacetate (MIA)-induced joint degeneration in rats is the most used animal model to screen analgesic drugs to alleviate osteoarthritis (OA) pain. This study aimed to evaluate the analgesic efficacy of pregabalin (PGB) in an MIA-induced OA model in rodents by using functional and neuroproteomic pain assessment methods. Treatment group included PGB in curative intent over 9 days compared to gold standard therapy (positive controls) and placebo (negative control). Functional assessments of pain (quantitative sensory testing and operant test) were performed concomitantly with spinal neuropeptides quantification. At day 21 post-OA induction, PGB in MIA rats reduced tactile allodynia (P = 0.028) and improved the place escape/avoidance behaviour (P = 0.04) compared to values recorded at last time-point before initiating analgesic therapy. All spinal neuropeptide concentrations, such as substance P, calcitonin gene-related peptide, bradykinin and somatostatin, came back to normal (non-affected) rat values, compared to their increase observed in MIA rats receiving the placebo (P < 0.0001). Initiated 13 days after chemical OA induction, repeated medication with PGB provided analgesia according to quantitative sensory testing, operant test and targeted neuropeptides pain assessment methods. This report highlights the interest of using reliable and sensitive methods like targeted neuropeptide quantification to detect the analgesic effects of a test article with concomitant functional assessments of pain when studying OA pain components.

10.
Arthritis Res Ther ; 21(1): 127, 2019 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-31126352

RESUMO

OBJECTIVE: To examine whether metformin use was associated with knee cartilage volume loss over 4 years and risk of total knee replacement over 6 years in obese individuals with knee osteoarthritis. METHODS: This study analysed the Osteoarthritis Initiative participants with radiographic knee osteoarthritis (Kellgren-Lawrence grade ≥ 2) who were obese (body mass index [BMI] ≥ 30 kg/m2). Participants were classified as metformin users if they self-reported regular metformin use at baseline, 1-year and 2-year follow-up (n = 56). Non-users of metformin were defined as participants who did not report the use of metformin at any visit from baseline to 4-year follow-up (n = 762). Medial and lateral cartilage volume (femoral condyle and tibial plateau) were assessed using magnetic resonance imaging at baseline and 4 years. Total knee replacement over 6 years was assessed. General linear model and binary logistic regression were used for statistical analyses. RESULTS: The rate of medial cartilage volume loss was lower in metformin users compared with non-users (0.71% vs. 1.57% per annum), with a difference of - 0.86% per annum (95% CI - 1.58% to - 0.15%, p = 0.02), after adjustment for age, gender, BMI, pain score, Kellgren-Lawrence grade, self-reported diabetes, and weight change over 4 years. Metformin use was associated with a trend towards a significant reduction in risk of total knee replacement over 6 years (odds ratio 0.30, 95% CI 0.07-1.30, p = 0.11), after adjustment for age, gender, BMI, Kellgren-Lawrence grade, pain score, and self-reported diabetes. CONCLUSIONS: These data suggest that metformin use may have a beneficial effect on long-term knee joint outcomes in those with knee osteoarthritis and obesity. Randomised controlled trials are needed to confirm these findings and determine whether metformin would be a potential disease-modifying drug for knee osteoarthritis with the obese phenotype.

11.
Artigo em Inglês | MEDLINE | ID: mdl-31126594

RESUMO

OBJECTIVES: The European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) sought to revisit the 2014 algorithm recommendations for knee osteoarthritis (OA), in light of recent efficacy and safety evidence, in order to develop an updated stepwise algorithm that provides practical guidance for the prescribing physician that is applicable in Europe and internationally. METHODS: Using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) process, a summary of evidence document for each intervention in OA was provided to all members of an ESCEO working group, who were required to evaluate and vote on the strength of recommendation for each intervention. Based on the evidence collected, and on the strength of recommendations afforded by consensus of the working group, the final algorithm was constructed. RESULTS: An algorithm for management of knee OA comprising a stepwise approach and incorporating consensus on 15 treatment recommendations was prepared by the ESCEO working group. Both "strong" and "weak" recommendations were afforded to different interventions. The algorithm highlights the continued importance of non-pharmacological interventions throughout the management of OA. Benefits and limitations of different pharmacological treatments are explored in this article, with particular emphasis on safety issues highlighted by recent literature analyses. CONCLUSIONS: The updated ESCEO stepwise algorithm, developed by consensus from clinical experts in OA and informed by available evidence for the benefits and harms of various treatments, provides practical, current guidance that will enable clinicians to deliver patient-centric care in OA practice.

12.
Mult Scler ; 25(4): 591-600, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-31081475

RESUMO

BACKGROUND: Obstetrical analgesia remains a matter of controversy because of the fear of neurotoxicity of local anesthetics on demyelinated fibers or their potential relationship with subsequent relapses. OBJECTIVE: To assess the impact of neuraxial analgesia on the risk of relapse during the first 3 months post-partum, with a focus on women who experienced relapses during pregnancy. METHODS: We analyzed data of women followed-up prospectively during their pregnancies and at least 3 months post-partum, collected in the Pregnancy in Multiple Sclerosis (PRIMS) and Prevention of Post-Partum Relapses with Progestin and Estradiol in Multiple Sclerosis (POPARTMUS) studies between 1992-1995 and 2005-2012, respectively. The association of neuraxial analgesia with the occurrence of a post-partum relapse was estimated by logistic regression analysis. RESULTS: A total of 389 women were included, 215 from PRIMS and 174 from POPARTMUS. In total, 156 women (40%) had neuraxial analgesia. Overall, 24% experienced a relapse during pregnancy and 25% in the 3 months post-partum. Women with a pregnancy relapse were more likely to have a post-partum relapse (odds ratio (OR) = 1.83, p = 0.02), independently of the use of neuraxial analgesia. There was no association between neuraxial analgesia and post-partum relapse (OR = 1.08, p = 0.78). CONCLUSION: Neuraxial analgesia was not associated with an increased risk of post-partum relapses, whatever multiple sclerosis (MS) activity during pregnancy.

13.
J Neurol Neurosurg Psychiatry ; 90(9): 1027-1038, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31072955

RESUMO

OBJECTIVE: To evaluate the accuracy of the recently proposed diagnostic criteria for chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS). METHODS: We enrolled 42 patients with hindbrain punctate and/or linear enhancements (<3 mm in diameter) and tested the CLIPPERS criteria. RESULTS: After a median follow-up of 50 months (IQR 25-82), 13 out of 42 patients were CLIPPERS-mimics: systemic and central nervous system lymphomas (n=7), primary central nervous system angiitis (n=4) and autoimmune gliopathies (n=2). The sensitivity and specificity of the CLIPPERS criteria were 93% and 69%, respectively. Nodular enhancement ( ≥ 3 mm in diameter), considered as a red flag in CLIPPERS criteria, was present in 4 out of 13 CLIPPERS-mimics but also in 2 out of 29 patients with CLIPPERS, explaining the lack of sensitivity. Four out of 13 CLIPPERS-mimics who initially met the CLIPPERS criteria displayed red flags at the second attack with a median time of 5.5 months (min 3, max 18), explaining the lack of specificity. One of these four patients had antimyelin oligodendrocyte glycoprotein antibodies, and the three remaining patients relapsed despite a daily dose of prednisone/prednisolone ≥ 30 mg and a biopsy targeting atypical enhancing lesions revealed a lymphoma. CONCLUSIONS: Our study highlights that (1) nodular enhancement should be considered more as an unusual finding than a red flag excluding the diagnosis of CLIPPERS; (2) red flags may occur up to 18 months after disease onset; (3) as opposed to CLIPPERS-mimics, no relapse occurs when the daily dose of prednisone/prednisolone is ≥ 30 mg; and (4) brain biopsy should target an atypical enhancing lesion when non-invasive investigations remain inconclusive.

14.
J Vasc Interv Radiol ; 30(7): 1116-1127, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30935868

RESUMO

PURPOSE: To evaluate if synovial inflammation and hypervascularization are present in a dog model of knee osteoarthritis and can be detected on conventional magnetic resonance imaging (MRI), dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), contrast-enhanced magnetic resonance imaging (CE-MRI), and quantitative digital subtraction angiography (Q-DSA) imaging. MATERIALS AND METHODS: Six dogs underwent MRI and angiography of both knees before and 12 weeks after right knee anterior cruciate ligament injury. Synovial vascularity was evaluated on CE-MRI, DCE-MRI, and Q-DSA by 2 independent observers. Synovial inflammation and vascularity were histologically scored independently. Cartilage lesions and osteophytes were analyzed macroscopically, and cartilage volumetry was analyzed by MRI. Vascularity and osteoarthritis markers on imaging were compared before and after osteoarthritis generation, and between the osteoarthritis model and the control knee, using linear mixed models accounting for within-dog correlation. RESULTS: In all knees, baseline imaging showed no abnormalities. Control knees did not develop significant osteoarthritis changes, synovial inflammation, or hypervascularization. In osteoarthritis knees, mean synovial enhancement score on CE-MR imaging increased by 13.1 ± 0.59 (P < .0001); mean synovial inflammation variable increased from 47.33 ± 18.61 to 407.97 ± 18.61 on DCE-MR imaging (P < .0001); and area under the curve on Q-DSA increased by 1058.58 ± 199.08 (P = .0043). Synovial inflammation, hypervascularization, and osteophyte formations were present in all osteoarthritis knees. Histology scores showed strong correlation with CE-MR imaging findings (Spearman correlation coefficient [SCC] = 0.742; P = .0002) and Q-DSA findings (SCC = 0.763; P < .0001) and weak correlation with DCE-MR imaging (SCC = -0.345; P = .329). Moderate correlation was found between CE-MR imaging and DSA findings (SCC = 0.536; P = .0004). CONCLUSIONS: In this early-stage knee osteoarthritis dog model, synovial inflammation and hypervascularization were found on imaging and confirmed by histology.

15.
Artigo em Inglês | MEDLINE | ID: mdl-31008553

RESUMO

OBJECTIVE: To examine whether joint line tenderness and patellofemoral grind from physical examination were associated with cartilage volume loss, worsening of radiographic osteoarthritis, and risk of total knee replacement. METHODS: This study examined 4353 Osteoarthritis Initiative participants. For each of joint line tenderness and patellofemoral grind, the patterns were defined as no (none at baseline and 1-year), fluctuating (present at either time-point), and persistent (present at both time-points). Cartilage volume loss and worsening of radiographic osteoarthritis over 4 years were assessed using magnetic resonance imaging and x-ray, and total knee replacement over 6 years was assessed. RESULTS: 35.0% participants had joint line tenderness, and 15.8% had patellofemoral grind. Baseline patellofemoral grind, but not joint line tenderness, was associated with increased cartilage volume loss (1.08%/year vs. 0.96%/year, p=0.02) and increased risk of total knee replacement [odds ratio (OR) 1.55, 95%CI 1.11-2.17, p=0.01]. While the patterns of joint line tenderness were not significantly associated with joint outcomes, participants with persistent patellofemoral grind had increased rate of cartilage volume loss (1.30%/year vs. 0.90%/year, p<0.001) and increased risk of total knee replacement (OR 2.10, 95%CI 1.30-3.38, p=0.002) compared with those without patellofemoral grind. CONCLUSIONS: Patellofemoral grind, but not joint line tenderness, may represent a clinical marker associated with accelerated cartilage volume loss over 4 years and increased risk of total knee replacement over 6 years. This simple clinical examination may provide clinicians with an inexpensive way to identify those at higher risk of disease progression who should be targeted for surveillance and management. This article is protected by copyright. All rights reserved.

16.
J Transl Med ; 17(1): 51, 2019 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-30786899

RESUMO

BACKGROUND: Inflammation and demyelination are the main processes in multiple sclerosis. Nevertheless, to date, blood biomarkers of inflammation are lacking. TWEAK, a transmembrane protein that belongs to the TNF ligand family, has been previously identified as a potential candidate. METHODS: Twenty-eight patients (9 males, 19 females) were prospectively included after a first clinical episode suggestive of multiple sclerosis and clinically followed during 3 years. Fifty-seven healthy controls were also included. TWEAK serum levels and MRI exams including magnetization transfer imaging were performed at baseline, 6- and 12-month follow-up. RESULTS: TWEAK serum levels were significantly increased in the patient group (mean baseline = 1086 ± 493 pg/mL, mean M6 = 624 ± 302 pg/mL and mean M12 = 578 ± 245 pg/mL) compared to healthy controls (mean = 467 ± 177 pg/mL; respectively p < 0.0001, 0.01 and 0.06). Serum levels of soluble TWEAK were significantly increased during relapses, compared to time periods without any relapse (respectively 935 ± 489 pg/mL and 611 ± 292 pg/mL, p = 0.0005). Moreover, patients presenting at least one gadolinium-enhanced CNS lesion at baseline (n = 7) displayed significantly increased serum TWEAK levels in comparison with patients without any gadolinium-enhanced lesion at baseline (n = 21) (respectively 1421 ± 657 pg/mL vs 975 ± 382 pg/mL; p = 0.02). Finally, no correlation was evidenced between TWEAK serum levels and the extent of brain tissue damage assessed by magnetization transfer ratio. CONCLUSIONS: The present study showed that TWEAK serum levels are increased in MS patients, in relation to the disease activity. This simple and reproducible serum test could be used as a marker of ongoing inflammation, contributing in the follow-up and the care of MS patients. Thus, TWEAK is a promising serum marker of the best window to perform brain MRI, optimizing the disease control in patients.

17.
Brain ; 142(3): 633-646, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30715195

RESUMO

Spinal cord lesions detected on MRI hold important diagnostic and prognostic value for multiple sclerosis. Previous attempts to correlate lesion burden with clinical status have had limited success, however, suggesting that lesion location may be a contributor. Our aim was to explore the spatial distribution of multiple sclerosis lesions in the cervical spinal cord, with respect to clinical status. We included 642 suspected or confirmed multiple sclerosis patients (31 clinically isolated syndrome, and 416 relapsing-remitting, 84 secondary progressive, and 73 primary progressive multiple sclerosis) from 13 clinical sites. Cervical spine lesions were manually delineated on T2- and T2*-weighted axial and sagittal MRI scans acquired at 3 or 7 T. With an automatic publicly-available analysis pipeline we produced voxelwise lesion frequency maps to identify predilection sites in various patient groups characterized by clinical subtype, Expanded Disability Status Scale score and disease duration. We also measured absolute and normalized lesion volumes in several regions of interest using an atlas-based approach, and evaluated differences within and between groups. The lateral funiculi were more frequently affected by lesions in progressive subtypes than in relapsing in voxelwise analysis (P < 0.001), which was further confirmed by absolute and normalized lesion volumes (P < 0.01). The central cord area was more often affected by lesions in primary progressive than relapse-remitting patients (P < 0.001). Between white and grey matter, the absolute lesion volume in the white matter was greater than in the grey matter in all phenotypes (P < 0.001); however when normalizing by each region, normalized lesion volumes were comparable between white and grey matter in primary progressive patients. Lesions appearing in the lateral funiculi and central cord area were significantly correlated with Expanded Disability Status Scale score (P < 0.001). High lesion frequencies were observed in patients with a more aggressive disease course, rather than long disease duration. Lesions located in the lateral funiculi and central cord area of the cervical spine may influence clinical status in multiple sclerosis. This work shows the added value of cervical spine lesions, and provides an avenue for evaluating the distribution of spinal cord lesions in various patient groups.

18.
Arthritis Rheumatol ; 71(7): 1056-1069, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30653843

RESUMO

OBJECTIVE: To assess the efficacy and safety of the anti-interleukin-1α/ß (anti-IL-1α/ß) dual variable domain immunoglobulin lutikizumab (ABT-981) in patients with knee osteoarthritis (OA) and evidence of synovitis. METHODS: Patients (n = 350; 347 analyzed) with Kellgren/Lawrence grade 2-3 knee OA and synovitis (determined by magnetic resonance imaging [MRI] or ultrasound) were randomized to receive placebo or lutikizumab 25, 100, or 200 mg subcutaneously every 2 weeks for 50 weeks. The coprimary end points were change from baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score at week 16 and change from baseline in MRI-assessed synovitis at week 26. RESULTS: The WOMAC pain score at week 16 had improved significantly versus placebo with lutikizumab 100 mg (P = 0.050) but not with the 25 mg or 200 mg doses. Beyond week 16, the WOMAC pain score was reduced in all groups but was not significantly different between lutikizumab-treated and placebo-treated patients. Changes from baseline in MRI-assessed synovitis at week 26 and other key symptom- and most structure-related end points at weeks 26 and 52 were not significantly different between the lutikizumab and placebo groups. Injection site reactions, neutropenia, and discontinuations due to neutropenia were more frequent with lutikizumab versus placebo. Reductions in neutrophil and high-sensitivity C-reactive protein levels plateaued with lutikizumab 100 mg, with further reductions not observed with the 200 mg dose. Immunogenic response to lutikizumab did not meaningfully affect systemic lutikizumab concentrations. CONCLUSION: The limited improvement in the WOMAC pain score and the lack of synovitis improvement with lutikizumab, together with published results from trials of other IL-1 inhibitors, suggest that IL-1 inhibition is not an effective analgesic/antiinflammatory therapy in most patients with knee OA and associated synovitis.

19.
Aging Clin Exp Res ; 31(1): 19-30, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30539541

RESUMO

BACKGROUND AND AIMS: Although osteoarthritis (OA) is managed mainly in primary care, general practitioners (GPs) are not always trained in its diagnosis, which leads to diagnostic delays, unnecessary resource utilization, and suboptimal patient outcomes. METHODS: To address this situation, an International Rheumatologic Board (IRB) of 8 experts from 3 continents developed guidelines for the diagnosis of OA in primary care. The focus was three major topologies: hip, knee, and hand/finger OA. The IRB used American College of Rheumatology diagnostic criteria. RESULTS: Care pathways based on clinical and radiological findings were developed to identify intervention thresholds for GPs/specialists. To optimize usefulness in the primary care setting, the guidelines were formatted as an uncomplicated, but comprehensive one-page decision tree for each topology, highlighting key aspects of the evaluation process and incorporating red flags. In a two-phase validation stage, the draft guidelines were evaluated by rheumatologists and GPs for project execution, content and perceived benefit. The strength of the guidelines lies in their user-friendly diagram and potential for broad application. Such guidelines will allow GPs to make an easy but definite diagnosis of OA and offer clear guidance about situations requiring an expert opinion. The guidelines have potential to improve patient outcomes and reduce the number of unnecessary procedures. DISCUSSION AND CONCLUSIONS: This project demonstrated the feasibility of developing easy-to-use and effective visual decision trees to facilitate the diagnosis and management of OA of the hip, knee and hand/finger in primary care. The next step should be to conduct a large impact study of implementation of these recommendations in the diagnostic management of OA in general practice in different areas.


Assuntos
Consenso , Árvores de Decisões , Osteoartrite/diagnóstico , Atenção Primária à Saúde/métodos , Algoritmos , Estudos de Viabilidade , Mãos , Articulação da Mão , Humanos , Osteoartrite do Quadril/diagnóstico , Osteoartrite do Joelho/diagnóstico
20.
Neuroimage ; 184: 901-915, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30300751

RESUMO

The spinal cord is frequently affected by atrophy and/or lesions in multiple sclerosis (MS) patients. Segmentation of the spinal cord and lesions from MRI data provides measures of damage, which are key criteria for the diagnosis, prognosis, and longitudinal monitoring in MS. Automating this operation eliminates inter-rater variability and increases the efficiency of large-throughput analysis pipelines. Robust and reliable segmentation across multi-site spinal cord data is challenging because of the large variability related to acquisition parameters and image artifacts. In particular, a precise delineation of lesions is hindered by a broad heterogeneity of lesion contrast, size, location, and shape. The goal of this study was to develop a fully-automatic framework - robust to variability in both image parameters and clinical condition - for segmentation of the spinal cord and intramedullary MS lesions from conventional MRI data of MS and non-MS cases. Scans of 1042 subjects (459 healthy controls, 471 MS patients, and 112 with other spinal pathologies) were included in this multi-site study (n = 30). Data spanned three contrasts (T1-, T2-, and T2∗-weighted) for a total of 1943 vol and featured large heterogeneity in terms of resolution, orientation, coverage, and clinical conditions. The proposed cord and lesion automatic segmentation approach is based on a sequence of two Convolutional Neural Networks (CNNs). To deal with the very small proportion of spinal cord and/or lesion voxels compared to the rest of the volume, a first CNN with 2D dilated convolutions detects the spinal cord centerline, followed by a second CNN with 3D convolutions that segments the spinal cord and/or lesions. CNNs were trained independently with the Dice loss. When compared against manual segmentation, our CNN-based approach showed a median Dice of 95% vs. 88% for PropSeg (p ≤ 0.05), a state-of-the-art spinal cord segmentation method. Regarding lesion segmentation on MS data, our framework provided a Dice of 60%, a relative volume difference of -15%, and a lesion-wise detection sensitivity and precision of 83% and 77%, respectively. In this study, we introduce a robust method to segment the spinal cord and intramedullary MS lesions on a variety of MRI contrasts. The proposed framework is open-source and readily available in the Spinal Cord Toolbox.


Assuntos
Processamento de Imagem Assistida por Computador/métodos , Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/patologia , Redes Neurais (Computação) , Medula Espinal/patologia , Humanos , Imagem por Ressonância Magnética/métodos , Variações Dependentes do Observador , Reconhecimento Automatizado de Padrão , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
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