Gender differences in factors associated with low quality of life and depression in Korean patients with ankylosing spondylitis.

PURPOSE: To identify predictors of low health-related quality of life (HRQoL) and depression in ankylosing spondylitis (AS) patients with a focus on gender differences. METHODS: We conducted a cross-sectional cohort study. Both AS-related clinical data and contextual factors were obtained. HRQoL and depressive mood were assessed by EuroQol-5 dimension (EQ-5D) and the Center for Epidemiological Studies Depression Scale (CES-D), respectively. Gender-stratified multivariable logistic regression analyses were performed. RESULTS: Among 211 patients, 161 were males. Males had similar disease activity and higher radiographic damage compared with females. There was no significant difference in EQ-5D index score between genders. CES-D score was higher in females. Higher ASDAS-C-reactive protein (CRP) was associated with low HRQoL in both males (Odds ratio [OR] 4.25, 95% confidence interval [CI] 2.42-7.46) and females (OR 2.94, 95% CI 1.02-8.48). Being employed was associated with decreased possibility of having low HRQoL in males (OR 0.39, 95% CI 0.16-0.95). Regarding depression, higher ASDAS-CRP (OR 1.87, 95% CI 1.03-3.40), current smoking (OR 2.98, 95% CI 1.09-8.15), and being employed (OR 0.17, 95% CI 0.06-0.46) were associated with depression in males. For females, living with a partner was related to depression (OR 0.08, 95% CI 0.01-0.93). CONCLUSION: AS patients with high disease activity are likely to be suffering from low HRQoL. Both disease-related factors and contextual factors were associated with depression, and predictors showed some differences between genders. Awareness of gender differences in comprehensive assessment can lead us to better personalized management in AS patients.

Low BASDAI score alone is not a good predictor of anti-tumor necrosis factor treatment efficacy in ankylosing spondylitis: a retrospective cohort study.

BACKGROUND: The purpose of this study was to determine the prevalence of high disease activity as measured using the Ankylosing Spondylitis Disease Activity Score (ASDAS) in ankylosing spondylitis (AS) patients who nonetheless have low Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores after anti-tumor necrosis factor (TNF) treatment. Its clinical impact on anti-TNF survival was also investigated. METHODS: We conducted a single-centre retrospective cohort study of AS patients having low BASDAI scores (< 4) and available ASDAS-C-reactive protein (CRP) data after 3 months of first-line anti-TNF treatment. Patients were grouped into high-ASDAS (≥ 2.1) and low-ASDAS (< 2.1) groups according to the ASDAS-CRP after 3 months of anti-TNF treatment. Their characteristics were compared. And survival analyses were carried out using Kaplan-Meier curves and log-rank test with the event being discontinuation of anti-TNF treatment due to lack/loss of efficacy. RESULTS: Among 116 AS patients with low BASDAI scores after 3 months of anti-TNF treatment, 38.8% were grouped into the high-ASDAS group. The high-ASDAS group tended to have greater disease activity after 9 months of treatment (BASDAI 2.9 ± 1.1 vs. 2.3 ± 1.4, p=0.007; ASDAS-CRP 1.8 ± 0.6 vs. 1.5 ± 0.7, p=0.079; proportion of high ASDAS-CRP 27.8% vs. 13.8%, p=0.094) and greater risk of discontinuing anti-TNF treatment due to lack/loss of efficacy than the low-ASDAS group (p=0.011). CONCLUSIONS: A relatively high proportion of AS patients with low BASDAI scores had high ASDAS-CRP. These low-BASDAI/high-ASDAS-CRP patients also had a greater risk for discontinuation of anti-TNF treatment due to low/lack of efficacy than the low-ASDAS group. The use of the ASDAS-CRP alone or in addition to the BASDAI may improve the assessment of AS patients treated with anti-TNF agents.

Reliability and Quality of Korean YouTube Videos for Education Regarding Gout.

BACKGROUND: YouTube has become an increasingly popular educational tool and an important source of healthcare information. We investigated the reliability and quality of the information in Korean-language YouTube videos about gout. METHODS: We performed a comprehensive electronic search on April 2, 2021, using the following keywords-"gout," "acute gout," "gouty arthritis," "gout treatment," and "gout attack"-and identified 140 videos in the Korean language. Two rheumatologists then categorized the videos into three groups: "useful," "misleading," and "personal experience." Reliability was determined using a five-item questionnaire modified from the DISCERN validation tool, and overall quality scores were based on the Global Quality Scale (GQS). RESULTS: Among the 140 videos identified, 105 (75.0%), 29 (20.7%), and 6 (4.3%) were categorized as "useful," "misleading," and "personal experience," respectively. Most videos in the "useful" group were created by rheumatologists (70.5%). The mean DISCERN and GQS scores in the "useful" group (3.3 ± 1.0 and 3.8 ± 0.7) were higher than those in the "misleading" (0.9 ± 1.0 and 1.9 ± 0.6) and "personal experience" groups (0.8 ± 1.2 and 2.0 ± 0.8) (P < 0.001 for both the DISCERN and GQS tools). CONCLUSION: Approximately 75% of YouTube videos that contain educational material regarding gout were useful; however, we observed some inaccuracies in the medical information provided. Healthcare professionals should closely monitor media content and actively participate in the development of videos that provide accurate medical information.

The risk factors and incidence of major infectious diseases in patients with ankylosing spondylitis receiving tumor necrosis factor inhibitors.

OBJECTIVES: This study aimed to evaluate the risk factor and incidence of infections in patients receiving tumor necrosis factor inhibitor (TNFi) therapy for ankylosing spondylitis using data from the national health insurance service. METHODS: This was a retrospective cohort study. Data regarding patients with ankylosing spondylitis prescribed TNFis were obtained from an insurance claims database of the Health Insurance Review & Assessment Service in Korea. Outcomes used were incidence rates of serious infection, pneumonia, tuberculosis, and herpes zoster during the follow-up period as well as the relationship between each TNFi and sex, hazard ratio (HR) of infection-related risk factors, and incidence of infections. RESULTS: A total of 2515 patients were included. There were no significant differences among the hazard ratios of TNFis for serious infection, pneumonia, and herpes zoster. However, the hazard ratio of tuberculosis was significantly higher for infliximab than for etanercept (adjusted HR 8.40 [95% confidence interval: 1.06-66.91]). In the subgroup analysis by sex, women treated with golimumab had a significantly higher hazard of herpes zoster than those treated with etanercept (adjusted HR 12.40 [95% confidence interval: 1.40-109.58]). CONCLUSION: We recommend that risk factors for these infectious diseases be identified prior to prescribing TNFis in these patients.

Tumour necrosis factor inhibitors slow radiographic progression in patients with ankylosing spondylitis: 18-year real-world evidence.

OBJECTIVES: Tumour necrosis factor inhibitors (TNFis) have been suggested to slow radiographic progression in patients with ankylosing spondylitis. However, limitations such as variations in disease activity, complex drug administration and short follow-up duration make it difficult to determine the effect of TNFis on radiographic progression. The aim of the study was to investigate whether long-term treatment with TNFis can reduce radiographic progression in patients with ankylosing spondylitis using 18-year longitudinal real-world data. METHODS: This retrospective study was conducted between January 2001 and December 2018 at a single centre. Among the 1280 patients whose electronic medical records were reviewed, data of 595 patients exposed to TNFis at least once were included. Among them, time intervals of TNFi exposure or non-exposure were determined in 338 patients ('on the TNFis' or 'off the TNFis' intervals, respectively). The difference in the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) change rate between 'on the TNFis' and 'off the TNFis' intervals was investigated. RESULTS: We obtained 2364 intervals of 338 patients (1281 'on the TNFis' and 1083 'off the TNFis' intervals). In the marginal structural model for inverse probability of treatment weighting, the change rate of mSASSS significantly decreased with the use of TNFis (ß=-0.112, p=0.004), and the adjusted mSASSS changes were 0.848 and 0.960 per year during 'on the TNFis' and 'off the TNFis' intervals, respectively. CONCLUSION: Compared with treatment without TNFis, treatment with TNFis slowed radiologic progression significantly.

A novel role for bone-derived cells in ankylosing spondylitis: Focus on IL-23.

The main aim of this study are to explore the role of bone-derived cells (BdCs) in ankylosing spondylitis (AS) and determine the underlying molecular mechanisms of IL-23 production. Primary BdCs were isolated from diced bone of facet joints obtained during surgery from seven AS patients and seven disease control (Ct) patients. Osteoblastic activity of BdCs was assessed by measuring their alkaline phosphatase activity and by alizarin red staining. Osteoblast and endoplasmic reticulum (ER) stress-related genes were assessed by quantitative PCR, immunoblotting, immunofluorescence, and immunohistochemistry. In addition, expression of IL-23 in response to BIX (selective BIP inducer X)-induced ER stress was evaluated by qPCR and ELISA. Protein interaction and binding to IL-23 promoter were confirmed by Immunoprecipitation and Chromatin immunoprecipitation, respectively. Transcript levels of genes involved in osteoblast function, as well as of the ER stress marker were higher in the AS group than the Ct group, and elevated RUNX2, BiP and IL-23 expression were observed in the BdCs, serum, and bone biopsies from the AS group. BIX-induced ER stress stimulated osteoblastic activity and IL-23 secretion by upregulating RUNX2 expression. Furthermore, in AS BdCs, RUNX2 interacted with C/EBPß to bind to IL-23 promoter and RUNX2 knockdown suppressed IL-23 secretion. These finding may provide a molecular mechanism involved in sustained ER stress in AS BdCs stimulates the activation of RUNX2 and C/EBPß genes, leading to IL-23 production.

Prevalence and distribution of sesamoid bones in the hand determined using digital tomosynthesis.

The aim of this study was to identify the prevalence and distribution of sesamoid bones in the hand using digital tomosynthesis (DTS) in comparison to previous studies. Using conventional radiography (CR) and DTS, hand images (81 left and 100 right) taken at a tertiary hospital were retrospectively reviewed. The sesamoid bones were identified in the interphalangeal (IP) and metacarpophalangeal (MCP) joints of the thumb (I), and in the distal interphalangeal (DIP) and metacarpophalangeal (MCP) of index (II), middle (III), ring (IV), and little (V) fingers. Differences in number of sesamoid bones detected on CR and DTS were analyzed. Sesamoid bones were observed in MCP I (100%), MCP II (46%), MCP III (2%), MCP IV (2%), MCP V (53%), and IP I (53%) on CR. Using DTS, sesamoid bones were found more often in MCP I (100%), MCP II (54%), MCP III (2%), MCP IV (1%), MCP V (59%), and IP I (75%). Differences in the mean number of sesamoid bones detected on CR and DTS were statistically significant. Sesamoid bones in DIP joints were frequently observed on DTS, but rarely found on CR. Most sesamoid bones in the hand were detected in MCP I, II, V, and IP I joints, and were more often detected on DTS than CR. DTS is a reliable tool to evaluate bony structures in the hand. Clin. Anat. 30:608-613, 2017. © 2017 Wiley Periodicals, Inc.

Prevalence and distribution of sesamoid bones and accessory ossicles of the foot as determined by digital tomosynthesis.

We previously reported that digital tomosynthesis (DTS) is a reliable tool for evaluating bony structures of the hand. The current study aimed to identify the prevalence and distribution of sesamoid bones and accessory ossicles of the foot using DTS and to compare the results to those of conventional radiography (CR). Foot images (DTS, 213; CR, 44) of 213 patients taken at a tertiary hospital were retrospectively reviewed. Sesamoid bones were identified in the metatarsaophalangeal (MTP), distal interphalangeal (DIP) and interphalangeal (IP) joints of the great (I), second (II), third (III), fourth (IV), and fifth (V) toes. Accessory ossicles were observed in the midfoot and hindfoot. The mean number of sesamoid bones and accessory ossicles was 3.9 ± 1.3 for the left foot and 3.7 ± 1.0 for the right foot on CR; and 3.9 ± 1.4 for the left foot and 3.9 ± 1.3 for the right foot on DTS. Sesamoid bones were observed in MTP I (100%), MTP II (5%), MTP III (2%), MTP IV (2%), MTP V (14%), and IP (68%) on CR. Sesamoid bones were observed in MTP I (100%), MTP II (8%), MTP III (1%), MTP IV (2%), MTP V (25%), and IP I(65%) on DTS. Among accessory ossicles, the most common bone identified was os tibiale externum (23% on CR and 33% on DTS) andos peroneum (14% on CR and 21% on DTS), and os trigonum (32% on CR and 0.5% on DTS). DTS was useful for finding sesamoid bones and accessory ossicles, although there were some limitations in observing the hindfoot. Clin. Anat. 30:1072-1076, 2017. © 2017 Wiley Periodicals, Inc.

Pericentral hydroxychloroquine retinopathy in Korean patients.

PURPOSE: A pericentral pattern of hydroxychloroquine (HCQ) retinopathy recently has been recognized in the United States in patients of Asian heritage. We report on an investigation of this pericentral retinopathy within a Korean population. DESIGN: Retrospective, observational study. PARTICIPANTS: Patients taking HCQ who were referred to ophthalmology for screening of HCQ retinopathy. METHODS: The medical records of patients were reviewed, including spectral domain optical coherence tomography, fundus autofluorescence, and visual fields. MAIN OUTCOME MEASURES: Frequency of pericentral pattern of HCQ retinopathy and features of progression. RESULTS: Among 218 patients referred, 9 (4.1%) were diagnosed with toxicity. Of these, 8 had a predominantly pericentral pattern of retinal change, whereas only 1 had the classic parafoveal distribution of retinal damage. Progression of retinopathy was documented in 3 patients followed more than 12 months while taking HCQ. No progression was seen in 2 patients without retinal pigment epithelial (RPE) damage who were followed for at least 12 months after discontinuation of HCQ. CONCLUSIONS: We found that a pericentral pattern of HCQ retinopathy was predominant among Korean patients, rather than the traditional (bull's eye) parafoveal pattern of damage. Retinopathy progressed while on the drug, but the progression stopped in patients with toxicity detected before RPE damage. These observations suggest the need for new approaches when screening for HCQ toxicity in Asian patients.

Clinicopathologic characteristics of IgG4-related retroperitoneal fibrosis among patients initially diagnosed as having idiopathic retroperitoneal fibrosis.

Abstract Objective. The purpose of our study was to determine the number of IgG4-related retroperitoneal fibrosis (RPF) cases that were initially diagnosed as idiopathic RPF and to investigate clinical characteristics of IgG4-related RPF. Methods. We retrospectively reviewed the medical records of 41 RPF patients who were treated at our tertiary care medical center in South Korea between January 2000 and January 2013. We identified cases of 19 patients in which a diagnosis was made based on percutaneous biopsy or surgery and selected these cases for further analysis. Immunostaining for IgG4 and histopathologic examinations were performed for pathology specimens. Results. In the 19 RPF patients, more than 30 IgG4-positive plasma cells per specimen were identified in 9 cases with dense lymphoplasmacytic infiltrates, storiform fibrosis, or obliterative phlebitis (IgG4-related RPF group). The recurrence rate of IgG4-related RPF was significantly higher than that of idiopathic RPF (67% vs. 10%, p = 0.015). Initial and cumulative steroid dosages were not different between the two groups. Conclusions. We found that 47% of the patients initially diagnosed with idiopathic RPF showed IgG4-related RPF evidence according to the pathology and IgG4-related RPF patients showed higher recurrence rate than idiopathic RPF patients. We suggest that maintenance immunosuppressive therapy is required in IgG4-related RPF patients.

Safety of resuming tumour necrosis factor inhibitors in patients who developed tuberculosis as a complication of previous TNF inhibitors.

OBJECTIVES: There is no consensus on whether restarting TNF inhibitors (TNFis) after treatment of an active tuberculosis (TB) infection caused by previous TNFi exposure is safe. In this study we sought to determine the safety of resuming TNFis in patients following TB treatment. METHODS: The medical records of all patients (n = 683) that received TNFi treatment at a single rheumatology clinic between June 2003 and December 2012 were retrospectively reviewed. Among them, data from patients who developed active TB infection were collected and patient outcomes were evaluated for those who resumed TNFis after TB treatment. RESULTS: Of 683 patients, 13 patients developed an active TB infection during TNFi treatment (4 on etanercept, 4 on adalimumab and 5 on infliximab). The median duration of TNFi treatment before TB infection was 20 months. TNFi treatment was reinitiated in six patients: four within 2 months after TB treatment and two after completion of TB treatment. Four patients reinitiated with the same TNFi, whereas two patients started with another TNFi. During a mean follow-up of 30.6 months, all six patients successfully completed TB treatment with no TB infection relapses. CONCLUSION: Our results suggest that resuming TNFi therapy in patients following adequate TB treatment is safe, even before completion of TB treatment.

Clinical features and prognosis in 82 patients with adult-onset Still's disease.

OBJECTIVES: To assess the clinical features, laboratory findings, and response to therapy according to disease course, and analyse the predictive factors for unfavourable outcomes in patients with adult-onset Still's disease (AOSD). METHODS: We retrospectively reviewed the medical records of 82 patients from January 1992 to December 2010 at a single tertiary hospital. Thirty-three had monocyclic disease, 33 experienced at least one relapse, and 14 had chronic disease. Patients were divided into those with favourable (monocyclic, n=33) and unfavourable (polycyclic or chronic and death, n=49) outcomes. RESULTS: The major clinical features were high spiking fever (96.3%), polyarthralgia (85.4%), skin rash (80.5%), myalgia (70.7%), and sore throat (68.3%). Analysis of prognostic factors for the 2 groups showed that polyarthralgia, elevated erythrocyte sedimentation rate, high serum lactate dehydrogenase, and low dose of initial glucocorticoids were related with unfavourable outcomes. An insufficient starting dosage of prednisolone or its equivalent (<30 mg/day) was the most significant predictive factor (OR 6.476, p=0.007) for chronic and relapsing disease, markedly decreasing response rates. CONCLUSIONS: Although AOSD is a benign disease, relapses are common and a chronic disease requires immunosuppressive therapy, that these unfavourable patients show significantly longer time from initiation of treatment to remission. Hence, it is important to control disease activity at the start of treatment with sufficient glucocorticoids.

Successful rituximab treatment of refractory hemophagocytic lymphohistiocytosis and autoimmune hemolytic anemia associated with systemic lupus erythematosus.

High-dose steroids, immunosuppressants such as cyclophosphamide and cyclosporine, and high-dose intravenous immunoglobulin have all been used to control hemophagocytic lymphohistiocytosis (HLH) or autoimmune hemolytic anemia (AIHA) associated with systemic lupus erythematosus (SLE); however, some patients are refractory to treatment. Rituximab has successfully resolved many of the refractory manifestations of SLE. Here, we report a case of HLH and AIHA associated with SLE that was refractory or intolerable to conventional therapy, but was successfully treated with rituximab.

Machine learning models with time-series clinical features to predict radiographic progression in patients with ankylosing spondylitis.

Objective: Ankylosing spondylitis (AS) is chronic inflammatory arthritis causing structural damage and radiographic progression to the spine due to repeated and continuous inflammation over a long period. This study establishes the application of machine learning models to predict radiographic progression in AS patients using time-series data from electronic medical records (EMRs). Methods: EMR data, including baseline characteristics, laboratory findings, drug administration, and modified Stoke AS Spine Score (mSASSS), were collected from 1,123 AS patients between January 2001 and December 2018 at a single center at the time of first (T1), second (T2), and third (T3) visits. The radiographic progression of the (n+1)th visit (Pn+1=(mSASSSn+1-mSASSSn)/(Tn+1-Tn)≥1 unit per year) was predicted using follow-up visit datasets from T1 to Tn. We used three machine learning methods (logistic regression with the least absolute shrinkage and selection operation, random forest, and extreme gradient boosting algorithms) with three-fold cross-validation. Results: The random forest model using the T1 EMR dataset best predicted the radiographic progression P2 among the machine learning models tested with a mean accuracy and area under the curves of 73.73% and 0.79, respectively. Among the T1 variables, the most important variables for predicting radiographic progression were in the order of total mSASSS, age, and alkaline phosphatase. Conclusion: Prognosis predictive models using time-series data showed reasonable performance with clinical features of the first visit dataset when predicting radiographic progression.

Protective effects of ginsenoside Rg3 on human osteoarthritic chondrocytes.

OBJECTIVES: To explore whether Rg3, a major and especially potent ginsenoside, modulates human osteoarthritic (OA) chondrocyte senescence. METHODS: Isolated chondrocytes were cultured in medium containing interleukin-1 beta (IL-1ß) with or without Rg3. The expression levels of mRNAs encoding aggrecan (ACAN), a major structural proteoglycan, type II collagen (COL2A1), and metalloproteinases (MMP) -1, -3, and -13, respectively, were determined using real-time PCR. Cellular senescence was detected by measuring senescence-associated ß-galactosidase (SA-ß-Gal) activity. Chondrocyte telomerase activity also served as a senescence marker. RESULTS: Chondrocytes stimulated by IL-1ß showed increased MMP-1, MMP-3, and MMP-13 levels, whereas the expression of COL2A1 and ACAN decreased. However, in cells co-treated with IL-1ß and Rg3, the levels of MMP-1 and MMP-13 were lower than in cells treated with IL-1ß alone, and COL2A1 and ACAN expression levels recovered from the low values seen when cultured only in the presence of IL-1ß. Also, compared to vehicle-treated controls, IL-1ß stimulation alone resulted in an increased number of SA-ß-Gal-positive cells, while co-incubation with IL-1ß and Rg3 significantly suppressed the expression of this senescence marker. Chondrocytes cultured with Rg3 showed significantly higher proliferative and telomerase activities than did control cells. CONCLUSIONS: These findings indicate that Rg3 protects the cell against the development of chondrocyte senescence in osteoarthritis.

The relationship between long-term use of nonsteroidal anti-inflammatory drugs and kidney function in patients with ankylosing spondylitis.

Objective: Although nonsteroidal anti-inflammatory drugs (NSAIDs) are the first-line treatment for ankylosing spondylitis (AS), their effect on kidney function remains unclear. This longitudinal study investigated the correlation between long-term NSAID use and kidney function in patients with AS using electronic medical records. Methods: The electronic medical records of 1,280 patients with AS collected from a single center between January 2001 and December 2018 were reviewed. The Assessment of Spondyloarthritis International Society (ASAS) NSAID Intake Score was used to determine the cumulative dose of all NSAIDs prescribed for a different time intervals. Each ASAS NSAID Intake Score was obtained for intervals of 6 months, 1 year, 2 years, 3 years, 5 years, and 10 years. The correlation between the ASAS NSAID Intake Score and final estimated glomerular filtration rate (eGFR) for each interval was investigated. Results: The mean ASAS Intake Scores for 6-month, 1-year, 2-year, 3-year, 5-year, and 10-year intervals were 55.30, 49.28, 44.84, 44.14, 44.61, and 41.17, respectively. At each interval, the pearson correlation coefficients were -0.018 (95% CI -0.031 to -0.006, p=0.004), -0.021 (95% CI -0.039 to -0.004, p=0.018), -0.045 (95% CI -0.071 to -0.019, p=0.001), -0.069 (95% CI -0.102 to -0.037, p<0.001), -0.070 (95% CI -0.114 to -0.026, p=0.002), -0.019 (95% CI -0.099 to 0.062, p=0.645), respectively. There was a very weak negative relationship between ASAS Intake Score and eGFR at each interval. Conclusion: Long-term NSAID use did not correlate with kidney function based on real-world data in patients with AS.

Radiographic involvement of cervical facet joints in ankylosing spondylitis: a longitudinal analysis in correlation with vertebral body lesions.

BACKGROUND: The inability to assess structural changes in facet joints is a limitation of established radiographic scoring systems for ankylosing spondylitis (AS). We compared radiographic evidence of ankylosis in cervical facet joints and cervical vertebral bodies in patients with AS. METHODS: We analysed longitudinal data collected from 1106 AS patients and assessed 4984 spinal radiographs obtained up to 16 years of follow-up. Comparisons between cervical facet joints and cervical vertebral bodies focused on the presence of ankylosis, which was defined by at least one facet joint exhibiting complete ankylosis (according to the method of de Vlam) or at least one vertebral body with a bridging syndesmophyte (according to the modified Stoke Ankylosing Spondylitis Spinal Score [mSASSS]). Ankylosis was assessed over time using spinal radiographs collected during follow-up periods stratified in 4-year increments. RESULTS: Patients with cervical facet joint ankylosis had higher cervical mSASSS, sacroiliitis grades, and inflammatory markers, with more prevalent hip involvement and uveitis. Overall, the numbers of spinal radiographs indicating ankylosis were comparable between cervical facet joints (17.8%) and cervical vertebral bodies (16.8%), and they usually presented together (13.5%). We observed similar proportions of radiographs with ankylosis only in cervical facet joints (4.3%) and cervical vertebral bodies (3.3%). As damage progressed, configurations with both cervical facet joint ankylosis and bridging syndesmophytes became more predominant with longer follow-up times, while configurations with cervical facet joint ankylosis only or bridging syndesmophytes only were less frequently observed. CONCLUSIONS: Evidence of cervical facet joint ankylosis appears as often as bridging syndesmophytes on routine AS spinal radiographs. Presence of cervical facet joint ankylosis should be considered because it may have a higher disease burden.

Association between changes in serum alkaline phosphatase levels and radiographic progression in ankylosing spondylitis.

This retrospective study evaluated the electronic medical records of patients with ankylosing spondylitis (AS) (January 2001-December 2018) to determine the relationship between serum alkaline phosphatase (ALP) levels and radiographic changes over time. Longitudinal data, including serum ALP levels, were imputed by linear interpolation at 3-month intervals. Among the serum ALP levels calculated for 8 years prior to modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) measurement, those having the highest beta coefficient with the mSASSS were selected in the correlation between ALP and longitudinal mSASSS. Linear mixed models with the selected serum ALP levels, mSASSS, and clinical variables were investigated. We included 1122 patients (mean follow-up, 8.20 [standard deviation: 2.85] years). The serum ALP level from 5 years and 3 months prior showed the highest beta coefficient with the mSASSS. In the linear mixed model, the serum ALP level at 5 years and 3 months before radiographic changes was significantly associated with the mSASSS (ß = 0.021, 95% confidence interval: 0.017-0.025, p < 0.001). Serum ALP levels measured approximately 5 years before may be a surrogate marker for predicting spinal radiographic changes. Long-term prospective clinical and experimental studies of > 5 years are required for biomarker discovery or therapeutic research on AS radiographic progression.

The influence of interleukin-32γ on osteoclastogenesis with a focus on fusion-related genes.

We previously reported that interleukin-32 gamma (IL-32γ) has a direct effect on osteoclast differentiation and activation in vitro in the context of receptor activator of NF-κB ligand (RANKL) co-stimulation. However, the stage of osteoclast differentiation at which IL-32γ exerts its effect was not determined. Here, we demonstrated that IL-32γ plays an important role in the fusion of preosteoclasts to yield multinuclear osteoclasts, particularly large osteoclasts. The synergistic effect of IL-32γ on RANKL-induced formation of multinuclear osteoclasts was readily apparent when cells were treated with IL-32γ at the fusion stage. In addition, we demonstrated that IL-32γ induced the expression of dendritic cell-specific transmembrane protein (DC-STAMP) and nuclear factor of activated T cells cytoplasmic 1 (NFATc1), and NFATc1 inactivation by cyclosporine treatment attenuated the effect of IL-32γ. These results indicate that IL-32γ is a potential mediator of osteoclast fusion, likely through up-regulation of NFATc1 and DC-STAMP.