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Radiologic and Pathological Investigation of Pseudarthrosis in Ankylosing Spondylitis: Distinguishing Between Inflammatory and Traumatic Etiology

期刊: JOURNAL OF RHEUMATOLOGY, 2019; 46 (3)

Objective. To investigate the pathogenesis of pseudarthrosis in ankylosing spondylitis (AS) based on the pathological analysis of specimens harvested during surgery. Methods. Radiographic and clinical data for 17 consecutive AS patients with pseudarthrosis were retrospectively analyzed. Meanwhile, the pathological analysis of specimens obtained during surgery was also performed. Results. In total, 18 extensive Andersson lesions were included. Pseudarthrosis located at the apical region were noted in 12 patients. Complete ossified anterior longitudinal ligaments above or below pseudarthrosis and fracture through posterior elements or facet joints were observed in 7 and 6 lesions, respectively. The most definitive pathological characteristic in all cases was proliferating hypovascular edematous fibrous tissue involving disc, bone-disc border, and vertebral body. Fibrinoid necrosis, necrotic bone fragments, hemosiderin deposits, and active subchondral osteogenesis were found, indicating trauma process. Mild perivascular collections of inflammatory cells were detected in only 2 cases. Conclusion. AS-related pseudarthrosis is more likely to originate from mechanical trauma than inflammation. The above-mentioned radiological and histological findings showed that multiple mechanisms lead to the formation of pseudarthrosis. These mechanisms include excessive stress, insufficiency fracture, and an acute fracture involving a 3-column structure.

IF:3.63

Monoclonal Gammopathy, Arthralgias, and Recurrent Fever Syndrome: A New Autoinflammatory Syndrome?

期刊: JOURNAL OF RHEUMATOLOGY, 2019; 46 (11)

Objective. To describe a new autoinflammatory syndrome with recurrent fever and monoclonal gammopathy that differs from Schnitzler syndrome. Methods. We conducted a retrospective study of patients with monoclonal gammopathy and recurrent fever of unknown origin. Results. Five patients were studied; median age at onset of symptoms was 44 years. Median frequency of fever attacks was 6 episodes per year. In the absence of treatment, the median duration of fevers was 3 days. Conclusion. This new autoinflammatory syndrome is defined by an association among monoclonal gammopathy, arthralgias, and recurrent fever.

IF:3.63

Clinical Outcomes and Clinico-pathological Correlations in Lupus Nephritis with Kidney Biopsy Showing Thrombotic Microangiopathy

期刊: JOURNAL OF RHEUMATOLOGY, 2019; 46 (11)

Objective. Renal thrombotic microangiopathy (TMA) is an uncommon pathological finding in lupus nephritis (LN), and its clinical significance remains to be defined. Methods. Twenty-four patients with lupus nephritis (LN) and renal TMA were selected from a retrospective review of 677 biopsy-proven LN patients, and compared with 48 LN controls without TMA (1:2 ratio) matched according to demographics and treatments. Results. Renal TMA was noted in 3.5% of kidney biopsies of LN. TMA was associated with a higher prevalence of anti-Ro (45.8% vs 18.8%; p = 0.016), higher Systemic Lupus Erythematosus Disease Activity Index scores (21.4 +/- 8.5 vs 10.8 +/- 2.3; p < 0.001), lower estimated glomerular filtration rate (eGFR; 16.8 +/- 11.7 ml/min vs 77.8 +/- 28.6 ml/min; p < 0.001), and a higher percentage of patients who required dialysis (37.5% vs 2.1%; p < 0.001) at the time of kidney biopsy. Activity and chronicity indices [median (range)] were higher in the TMA group [11 (2-19) and 3 (1-8), respectively, compared with 7 (0-15) and 1 (0-3) in controls; p = 0.004 and p < 0.001; respectively]. Patients with TMA showed inferior 5-year renal survival and higher incidence of chronic kidney disease at last followup (70% and 66.6%, respectively, compared with 95% and 29.2% in controls; p = 0.023 and 0.002, respectively). The TMA group also showed lower median eGFR compared with controls [50.1 (IQR 7-132) ml/min vs 85.0 (IQR 12-147) ml/min; p = 0.003]. Five-year patient survival rate was similar between the 2 groups (87% and 98% in TMA and control group, respectively; p = 0.127). Conclusion. TMA in kidney biopsy was associated with more severe clinical and histological activity, and significantly inferior longterm renal outcome in LN.

IF:3.63

Detection of Erosions in Sacroiliac Joints of Patients with Axial Spondyloarthritis Using the Magnetic Resonance Imaging Volumetric Interpolated Breath-hold Examination

期刊: JOURNAL OF RHEUMATOLOGY, 2019; 46 (11)

Objective. The volumetric interpolated breath-hold examination (VIBE) magnetic resonance imaging (MRI) technique can visualize erosive cartilage defects in peripheral joints. We evaluated the ability of VIBE to detect erosions in sacroiliac joints (SIJ) of patients with axial spondyloarthritis (axSpA) compared to the established T1-weighted MRI sequence and computed tomography (CT). Methods. MRI (T1-weighted and VIBE) and CT scans of SIJ of 109 patients with axSpA were evaluated by 2 blinded readers based on SIJ quadrants (SQ). Erosions were defined according to Assessment of Spondyloarthritis international Society (ASAS) definitions. Scores were recorded if readers were in agreement. Results. Erosions were less frequently detected by CT (153 SQ) than by T1-weighted MRI (182 SQ; p = 0.008) and VIBE-MRI (199 SQ; p < 0.001 vs CT and p = 0.031 vs T1-weighted MRI). Taking CT as the gold standard, the sensitivity of VIBE-MRI (71.2%) was higher than that for T1-weighted MRI (63.4%), with similar specificity (87.3% vs 88%, respectively). In linear regression analysis, younger age was significantly associated with occurrence of erosions independently in VIBE-MRI (beta = 0.384, p < 0.001) and T1-weighted MRI (beta = 0.369, p < 0.001) compared to CT. Conclusion. The VIBE-MRI sequence was more sensitive than T1-weighted MRI in identifying erosive damage in the SIJ, especially in younger patients. This might be due to the ability of VIBE-MRI to identify structural changes in the cartilage that have not yet extended to the underlying bone, where CT seems to be superior.

IF:3.63

Contrast-enhanced Ultrasonography for Monitoring Arterial Inflammation in Takayasu Arteritis

期刊: JOURNAL OF RHEUMATOLOGY, 2019; 46 (6)

Objective. To evaluate the utility of contrast-enhanced ultrasound (CEUS) compared with 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) in assessing vessel inflammation of Takayasu arteritis (TA). Methods. This is a retrospective analysis of 71 patients with TA who had undergone carotid CEUS. Twenty-two of 71 patients underwent FDG-PET after CEUS. Clinical disease activity was assessed by Kerr criteria and the Indian Takayasu Clinical Activity Score 2010 (ITAS2010). We investigated the correlation between carotid vascularization on CEUS and clinical data. The consistency of carotid CEUS and PET data has been analyzed for TA disease activity. Results. There was a statistically significant correlation between the results of CEUS and ITAS2010 (p = 0.004) or Kerr criteria (p < 0.001). According to ITAS2010, thirty-four of 71 patients with TA were clinically inactive. Assessment of 34 TA patients with clinically inactive disease yielded 11 CEUS scans that showed active lesions (visual grade = 2) in the left or right carotid artery. In 22 cases that underwent CEUS and FDG-PET, 12 were active and 10 were inactive on the basis of ITAS2010. Moreover, bilateral carotid CEUS vascularization score positively correlated with vascular FDG uptake in these patients with TA (p = 0.004). When vascular inflammation was defined as FDG uptake with visual grade = 2, carotid CEUS showed sensitivity of 100% and specificity of 80%. Conclusion. For TA patients with clinically inactive disease, CEUS could help clinicians to identify active lesions in the carotid vascular region. Carotid CEUS may be a rapid and cost-effective imaging tool in the followup of patients with TA.

IF:3.63

Improvement of Outcomes in Patients with Lupus Nephritis: Management Evolution in Chinese Patients from 1994 to 2010

期刊: JOURNAL OF RHEUMATOLOGY, 2019; 46 (8)

Objective. To assess how the longterm outcomes have changed over the past decades in Chinese patients with lupus nephritis (LN). The trends in patient manifestation at presentation, treatment pattern, and therapeutic effects were evaluated. Methods. A cohort of biopsy-proven patients with LN (n = 1945) from January 1994 to December 2010 was analyzed. Treatment regimens, treatment response, renal relapse, and renal outcome were compared at different time periods (1994-1998, 1999-2004, and 2005-2010). Results. Patients in the later periods had shorter duration of disease, lower serum creatinine value and chronicity at biopsy, and more frequent followup. They were more likely to receive standard-of-care therapies, which included cyclophosphamide, mycophenolate mofetil, and combination therapy. Patients in the later periods had higher probabilities of achieving remission (p < 0.001) and lower probabilities of experiencing renal flare (p = 0.007). The 5-year renal survival rates were 92.6%, 90.6%, and 94.3% in 1994-1998, 1999-2004, and 2005-2010, respectively. The 5-year risk of endstage renal disease (ESRD) did not differ between 1994-1998 and 1999-2004, but was significantly lower in 2005-2010 (HR 0.40, 95% CI 0.19-0.85 vs 1999-2004). In multivariable Cox analysis, standard therapy was independently associated with lower risk of ESRD (adjusted HR 0.72, 95% CI 0.52-0.98, p = 0.04). Variables of renal damage at biopsy (renal function, activity index, and chronicity index) were independently associated with poor outcome. Conclusion. The outcomes of Chinese patients with LN have improved from 1994 to 2010. With the increased use of standard therapies, the remission rates have increased and renal relapse has decreased.

IF:3.63

Musculoskeletal Ultrasound in Systemic Lupus Erythematosus: Systematic Literature Review by the Lupus Task Force of the OMERACT Ultrasound Working Group

期刊: JOURNAL OF RHEUMATOLOGY, 2019; 46 (10)

Objective. To identify and synthesize the best available evidence on the application of musculoskeletal (MSK) ultrasound (US) in patients with systemic lupus erythematosus (SLE) and to present the measurement properties of US in different elementary lesions and pathologies. Methods. A systematic literature search of PubMed, Embase, and the Cochrane Library was performed. Original articles were included that were published in English between August 1, 2014, and December 31, 2018, reporting US, Doppler, synovitis, joint effusion, bone erosion, tenosynovitis, and enthesitis in patients with SLE. Data extraction focused on the definition and quantification of US-detected synovitis, joint effusion, bone erosion, tenosynovitis, enthesitis, and the measurement properties of US according to the OMERACT Filter 2.1 instruments selection. Results. Of the 143 identified articles, 15 were included. Most articles were cross-sectional studies (14/15, 93%). The majority of the studies used the OMERACT definitions for ultrasonographic pathology. Regarding the measurement properties of US in different elementary lesions and pathologies, all studies dealt with face validity, content validity, and feasibility. Most studies achieved construct validity. Concerning the reliability of image reading, 1 study (1/15, 7%) assessed both intraobserver and interobserver reliability. For image acquisition, 4 studies (4/15, 27%) evaluated interobserver reliability and none had evaluated intraobserver reliability. Criterion validity was assessed in 1 study (1/15, 7%). Responsiveness was not considered in any of the studies. Conclusion. This literature review demonstrates the need for further research and validation work to define the involvement of US as an outcome measurement instrument for the MSK manifestations in patients with SLE.

IF:3.63

Role of MiR-98 and Its Underlying Mechanisms in Systemic Lupus Erythematosus

期刊: JOURNAL OF RHEUMATOLOGY, 2018; 45 (10)

Objective. T-Iymphocyte apoptosis plays a critical role in the pathogenesis of systemic lupus erythematosus (SLE). However, the underlying regulatory mechanisms of apoptosis in SLE remain unclear. The aim of this study was to explore the role of miR-98 in SLE and its underlying mechanisms. Methods. Western blotting and quantitative reverse transcription PCR (qRT-PCR) were used to analyze miR-98 and Fas expression. Luciferase reporter assays were performed to identify miR-98 targets. To modify miRNA levels, miR-98 mimics and inhibitor were transfected into cells. A lentiviral construct was used to overexpress the level of Fas in SLE CD4+ T cells. Gene and protein expression were determined by qRT-PCR and Western blotting. Apoptosis levels were evaluated by annex in V staining and flow cytometry. Results. Compared to those of healthy donors, miR-98 was dowuegulated in SLE CD4+ T cells, whereas Fas mRNA and protein expression were upregulated. Upregulation of miR-98 by mimic transfection protected Jurkat cells against Fas-mediated apoptosis at both mRNA and protein levels, while miR-98 inhibitor induced the completely opposite effect. Luciferase reporter assays demonstrated that miR-98 directly targeted Fas mRNA. Further, miR-98 inhibitor induced apoptosis in primary healthy CD4+ T cells through the Fas-caspase axis, while upregulation of miR-98 in SLE CD4+ T cells led to the opposite effect. Conclusion. The current study revealed that downregulation of miR-98 induces apoptosis by modulating the Fas-mediated apoptotic signaling pathway in SLE CD4+ T cells. These results suggest that miR-98 might serve as a potential target for SLE treatment.

IF:3.63

Rheumatoid Arthritis and Risk of Sexual Dysfunction: A Systematic Review and Metaanalysis

期刊: JOURNAL OF RHEUMATOLOGY, 2018; 45 (10)

Objective. It has been reported that there is an association between rheumatoid arthritis (RA) and increased susceptibility to sexual dysfunction (SD). This systematic review and metaanalysis aimed to investigate whether RA was a risk factor for SD. Methods. MEDLINE (PubMed), EMBASE, and the Cochrane Library were systematically searched for all studies assessing sexual function in patients with RA. The association between RA and risk of SD was summarized using relative risk (RR) with 95% CI. Results. Overall, 44,745 participants (mean age 43.2 yrs) were included from 7 studies (4 cross-sectional and 3 case-control studies). Of these, 6642 were patients with RA, with the mean disease duration from 5.7 years to 12.17 years. The methodological qualities of the included studies were judged as moderate to high. Synthesis of results demonstrated that RA was significantly associated with an increased risk of SD in females (RR 1.73, 95% CI 1.36-2.22, p < 0.001; heterogeneity: I2 60.3%, p = 0.028) as well as in males (RR 1.99, 95% CI 1.64-2.43, p < 0.001). The outcomes related to the Grading of Recommendations Assessment, Development, and Evaluation approach showed that the absolute effect of RA on SD was 10 more per 1000 (6-15 more); the overall quality of evidence was rated as low. Conclusion. Evidence from included studies indicates that patients with RA have a significantly increased risk of SD, which suggests that both patients and clinicians should be aware of the potential role of RA in the development of SD.

IF:3.63

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