Publications by authors named "Yong-Beom Park"

282 Publications

D-dimer predicts poor hospitalisation outcomes in patients with antineutrophil cytoplasmic autoantibody-associated vasculitis.

Clin Exp Rheumatol 2021 Feb 25. Epub 2021 Feb 25.

Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, and Severance Institute for Vascular and Metabolic Research, Yonsei University College of Medicine, Seoul, South Korea.

Objectives: The in-hospital mortality rate among patients with antineutrophil cytoplasmic autoantibody-associated vasculitis (AAV) is high. Unfortunately, there is no reliable prognostic biomarker. This study aimed to investigate whether elevated D-dimer levels can predict hospitalisation outcomes among patients with AAV.

Methods: We performed a retrospective analysis at a tertiary medical centre in Seoul, South Korea, between 2005 and 2019. Patients with AAV requiring hospitalisation, whose D-dimer levels were available within one week of hospitalisation, were included; patients with known alternative reasons for elevated D-dimer were excluded. Death and intensive care unit requirements were defined as adverse outcomes.

Results: In total, 61 AAV patients with a total of 100 episodes of hospitalisation were included. Median D-dimer levels were significantly higher in patients with adverse outcomes than in those without adverse outcomes (1.84 vs. 0.42 mg/dL; p=0.006). Consistently, the incidence of the adverse outcomes was significantly higher in the high D-dimer group (≥0.699 mg/dL; n = 40) than in the low D-dimer group (<0.699 mg/dL; n = 60) (35% vs. 10%; p=0.002). Multivariate logistic regression analysis revealed that a high D-dimer level was a significant risk factor for adverse outcomes (hazard ratio, 4.852; 95% confidence interval, 1.320-17.833; p=0.017). Kaplan-Meier survival analysis revealed that the high D-dimer group was associated with more 30-day in-hospital adverse outcomes than the low D-dimer group (p=0.008).

Conclusions: High D-dimer levels on admission are significantly associated with adverse outcomes among patients with AAV.
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February 2021

Fibrosis-5 predicts end-stage renal disease in patients with microscopic polyangiitis and granulomatosis with polyangiitis without substantial liver diseases.

Clin Exp Med 2021 Feb 20. Epub 2021 Feb 20.

Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, Republic of Korea.

We previously reported that fibrosis-4 (FIB-4) was associated with poor outcomes of microscopic polyangiitis (MPA) and granuloma with polyangiitis (GPA). We also investigated the potential of FIB-5, a novel index, in predicting all-cause mortality and end-stage renal disease (ESRD) during follow-up in patients with MPA and GPA without substantial liver diseases. Clinical and laboratory data at diagnosis were collected by reviewing the medical records of 180 patients with MPA and GPA. FIB-5 was obtained by a following equation: FIB-5 = (serum albumin (g/L) × 0.3 + platelet count (10/L) × 0.05) - (alkaline phosphatase (IU/L) × 0.014 + aspartate aminotransferase/alanine aminotransferase ratio × 6 + 14). The median age of the patients at diagnosis was 61.0 years. FIB-5 at diagnosis could not reflect the cross-sectional vasculitis activity. The cutoffs of FIB-5 for poor outcomes was set as 0.82 (the lowest tertile) and -0.42 (the lowest quartile) at diagnosis. In Kaplan-Meier survival analysis, patients with FIB-5 < 0.82 and those with FIB-5 < -0.42 exhibited lower ESRD-free survival rates than those without. However, it could not predict all-cause mortality. In multivariable Cox hazards analysis, both FFS (Hazard ratio (HR) 1.554) and FIB-5 < 0.82 (HR 2.096) as well as both FFS (HR 1.534) and FIB-5 < -0.42 (HR 2.073) at diagnosis independently predicted ESRD during follow-up. In conclusion, FIB-5 < 0.82 and FIB-5 < -0.42 at diagnosis could predict the occurrence of ESRD, but not all-cause mortality, during follow-up in patients with MPA and GPA without substantial liver diseases.
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http://dx.doi.org/10.1007/s10238-021-00691-2DOI Listing
February 2021

Fibrinogen to albumin ratio reflects the activity of antineutrophil cytoplasmic antibody-associated vasculitis.

J Clin Lab Anal 2021 Feb 16:e23731. Epub 2021 Feb 16.

Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.

Background: We investigated whether fibrinogen to albumin ratio (FAR) at diagnosis could reflect the cross-sectional activity and predict poor outcomes in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).

Methods: This cross-sectional study included 54 immunosuppressant drug-naïve patients with AAV who had the results of plasma fibrinogen and serum albumin at diagnosis. Clinical and laboratory data at diagnosis were collected, and all-cause mortality, cerebrovascular accident, cardiovascular disease, end-stage renal disease occurrences were assessed as poor outcomes. FAR was calculated by the following equation: FAR = plasma fibrinogen (g/dl)/serum albumin (g/dl).

Results: The median age was 65.5 years, and 59.3% of patients were men (33 MPA, 13 GPA and 8 EGPA). FAR was significantly correlated with Birmingham vasculitis activity score (BVAS; r = 0.271), erythrocyte sedimentation rate (ESR; r = 0.668) and C-reactive protein (CRP; r = 0.638). High BVAS was defined as BVAS ≥16, and the cut-off of FAR at diagnosis was set as 0.118. AAV patients with FAR at diagnosis ≥0.118 had a significantly higher risk for the cross-sectional high BVAS than those without (RR 3.361). In the univariable linear regression analysis, CRP (β = 0.383) and FAR (β = 0.297) were significantly correlated with BVAS at diagnosis. However, in the multivariable analysis, none of them was correlated with the cross-sectional BVAS. FAR at diagnosis could not predict poor outcomes during follow-up in AAV patients.

Conclusions: Fibrinogen to albumin ratio at diagnosis could reflect the cross-sectional BVAS but could not predict poor outcomes in patients with AAV.
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http://dx.doi.org/10.1002/jcla.23731DOI Listing
February 2021

A clinical comparison of an endothelin receptor antagonist and phosphodiesterase-5 inhibitors for treating digital ulcers of systemic sclerosis.

Rheumatology (Oxford) 2021 Feb 12. Epub 2021 Feb 12.

Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, South Korea.

Objectives: To assess the efficacy of an endothelin receptor antagonist (ERA) and phosphodiesterase-5 inhibitors (PDE5i) for treating systemic sclerosis (SSc)-related digital ulcers (DUs).

Methods: This prospective, multicenter, observational cohort study recruited patients with active SSc-related DUs from 13 medical centers in South Korea. The primary outcome was time to cardinal ulcer (CU) healing. Secondary outcomes included time to new DU occurrence. Patients were followed up 4, 8, 12, and 24 weeks after treatment initiation.

Results: Sixty-three patients were analyzed. Their mean age was 49.9 ± 11.4 years and 49 were female. Twenty-eight had limited SSc. Forty-nine patients received the ERA, 11 patients received a PDE5i (nine sildenafil, one udenafil, and one tadalafil), and three patients received other medication. The hazard ratio (HR) for time to CU healing in the ERA group versus the PDE5i group was 0.75 (95% CI: 0.35-1.64, p = 0.47) in an unadjusted model and 0.80 (95% CI: 0.36-1.78, p = 0.59) in a model adjusted for age, sex, use of calcium channel blockers (CCBs), total DU numbers, and initial CU area. The HR for new DU development in the ERA group versus the PDE5i group was 0.39 (95% CI: 0.16-0.93, p = 0.03) in an unadjusted model and 0.32 (95% CI: 0.13-0.81, p = 0.02) in an adjusted model. No patients receiving CCBs developed new DUs at 24 weeks.

Conclusion: Time to CU healing is comparable for ERA and PDE5i. An ERA is more effective in reducing new DU occurrence than PDE5i. CCBs may be effective as a background medication.
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http://dx.doi.org/10.1093/rheumatology/keab147DOI Listing
February 2021

Diagnostic Accuracy of Magnetic Resonance Imaging in the Detection of Type and Location of Meniscus Tears: Comparison with Arthroscopic Findings.

J Clin Med 2021 Feb 5;10(4). Epub 2021 Feb 5.

Department of Orthopedic Surgery, Chung-Ang University Hospital, Chung-Ang University College of Medicine, 102 Heukseok-ro, Dongjak-gu, Seoul 06973, Korea.

Magnetic resonance imaging (MRI) has been widely used for the diagnosis of meniscal tears, but its diagnostic accuracy, depending on the type and location, has not been well investigated. We aimed to evaluate the diagnostic accuracy of MRI by comparing MRI and arthroscopic findings. Preoperative 3.0-T MRI and arthroscopic findings from 2005 to 2018 were reviewed to determine the presence, type, and location of meniscus tears. In addition, subgroup analysis was performed according to anterior cruciate ligament (ACL) injury. The exclusion criteria were as follows: (1) Inflammatory arthritis, (2) other ligament injuries, (3) inability to classify meniscal tears due to degenerative arthritis, (4) over 90 days from MRI to surgery, and (5) incomplete data. Of the 2998 eligible patients, 544 were finally included. The sensitivity and specificity of MRI in determining medial and lateral meniscus tears were 91.8% and 79.9%, and 80.8% and 85.4%, respectively. The accuracy of MRI in the ACL-injured group was lower than that in the ACL-intact group (medial meniscus: 81.7% vs. 88.1%, = 0.041; 72.9% vs. lateral meniscus: 88.0%, < 0.001). MRI accuracy was low for the longitudinal tears of the posterior horn of the medial meniscus in the ACL-injured group. MRI could be a diagnostic tool for meniscus tears, but has limited accuracy in their classification of the type and location. Hence, care should be taken during arthroscopic assessment of ACL-injured patients due to low diagnostic accuracy of preoperative MRI.
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http://dx.doi.org/10.3390/jcm10040606DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914628PMC
February 2021

Antineutrophil Cytoplasmic Antibody Positivity Is Associated with Vascular Involvement in Behçet's Disease.

Yonsei Med J 2021 Feb;62(2):149-158

Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.

Purpose: We investigated whether antineutrophil cytoplasmic antibody (ANCA) positivity is associated with vascular manifestations at diagnosis of Behçet's disease (BD) and poor outcomes during follow-up.

Materials And Methods: We retrospectively reviewed the medical records of 1060 patients with BD. Among them, 808 patients could be diagnosed with BD based on the revised version of the International Criteria for Behçet's Disease (ICBD) in 2014 (2014 ICBD criteria) and 588 patients could be diagnosed with BD based on the International Study Group (ISG) criteria proposed in 1990 (1990 ISG criteria). We examined the sites and patterns of vascular involvement in the BD patients at diagnosis and evaluated adverse outcomes during follow up, such as all-cause mortality, acute coronary syndrome, and deep vein thrombosis.

Results: Among the 808 patients with BD based on the 2014 ICBD criteria, the rate of ANCA positivity at diagnosis was 2.2%. ANCA-positive BD patients exhibited a higher frequency of overall vascular manifestations (22.2% vs. 6.1%) and higher frequencies of vascular involvement in the upper extremities and visceral arteries than ANCA-negative BD patients (5.6% vs. 0.1% and 5.6% vs. 0.1%). Among the 588 BD patients based on the 1990 ISG criteria, similarly, ANCA-positive BD patients exhibited a higher frequency of vascular manifestations than ANCA-negative BD patients. ANCA positivity, however, did not seem to be associated with poor outcomes in BD patients during follow up.

Conclusion: ANCA positivity in BD patients was found to be associated with cross-sectional vascular involvement in the upper extremities and visceral arteries at diagnosis but was not predictive of poor outcomes during follow-up.
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http://dx.doi.org/10.3349/ymj.2021.62.2.149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859684PMC
February 2021

Clinical Efficacy of Platelet-Rich Plasma Injection and Its Association With Growth Factors in the Treatment of Mild to Moderate Knee Osteoarthritis: A Randomized Double-Blind Controlled Clinical Trial As Compared With Hyaluronic Acid.

Am J Sports Med 2021 02;49(2):487-496

Department of Orthopedic Surgery, Himchan Hospital, Busan, Republic of Korea.

Background: Although platelet-rich plasma (PRP) has potential as a regenerative treatment for knee osteoarthritis, its efficacy varies. Compositional differences among types of PRP could affect clinical outcomes, but the biological characterization of PRP is lacking.

Purpose: To assess the efficacy of intra-articular PRP injection in knee osteoarthritis as compared with hyaluronic acid (HA) injection and to determine whether the clinical efficacy of PRP is associated with its biological characteristics.

Study Design: Randomized controlled trial; Level of evidence, 1.

Methods: A total of 110 patients with symptomatic knee osteoarthritis received a single injection of leukocyte-rich PRP (1 commercial kit) or HA. Clinical data were assessed at baseline and at 6 weeks and 3 and 6 months after injection. The primary endpoint was an improvement in the International Knee Documentation Committee (IKDC) subjective score at 6 months, and the secondary endpoints were improvements in scores based on the Patient Global Assessment, the visual analog scale (VAS) for pain, the Western Ontario and McMaster Universities Osteoarthritis Index, and the Samsung Medical Center patellofemoral score. Cell counts and concentrations of growth factors and cytokines in the injected PRP were assessed to determine their association with clinical outcomes.

Results: PRP showed significantly improvement in IKDC subjective scores at 6 months (11.5 in the PRP group vs 6.3 in the HA group; = .029). There were no significant differences between groups in other clinical outcomes. The Patient Global Assessment score at 6 months was better in the PRP group ( = .035). The proportion of patients who scored above the minimal clinically important difference (MCID) for VAS at 6 months was significantly higher in the PRP group ( = .044). Within the PRP group, the concentrations of platelet-derived growth factors were high in patients with a score above the MCID for VAS at 6 months. The incidence of adverse events did not differ between the groups ( > .05).

Conclusion: PRP had better clinical efficacy than HA. High concentrations of growth factors were observed in patients who scored above the MCID for clinical outcomes in the PRP group. These findings indicate that concentration of growth factors needs to be taken into consideration for future investigations of PRP in knee osteoarthritis.

Registration: NCT02211521 (ClinicalTrials.gov identifier).
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http://dx.doi.org/10.1177/0363546520986867DOI Listing
February 2021

Allogeneic Umbilical Cord Blood-Derived Mesenchymal Stem Cell Implantation Versus Microfracture for Large, Full-Thickness Cartilage Defects in Older Patients: A Multicenter Randomized Clinical Trial and Extended 5-Year Clinical Follow-up.

Orthop J Sports Med 2021 Jan 12;9(1):2325967120973052. Epub 2021 Jan 12.

Department of Orthopedic Surgery, Korea University Guro Hospital, Korea University School of Medicine, Seoul, Republic of Korea.

Background: There is currently no optimal method for cartilage restoration in large, full-thickness cartilage defects in older patients.

Purpose: To determine whether implantation of a composite of allogeneic umbilical cord blood-derived mesenchymal stem cells and 4% hyaluronate (UCB-MSC-HA) will result in reliable cartilage restoration in patients with large, full-thickness cartilage defects and whether any clinical improvements can be maintained up to 5 years postoperatively.

Study Design: Randomized controlled trial; Level of evidence, 1.

Methods: A randomized controlled phase 3 clinical trial was conducted for 48 weeks, and the participants then underwent extended 5-year observational follow-up. Enrolled were patients with large, full-thickness cartilage defects (International Cartilage Repair Society [ICRS] grade 4) in a single compartment of the knee joint, as confirmed by arthroscopy. The defect was treated either with UCB-MSC-HA implantation through mini-arthrotomy or with microfracture. The primary outcome was proportion of participants who improved by ≥1 grade on the ICRS Macroscopic Cartilage Repair Assessment (blinded evaluation) at 48-week arthroscopy. Secondary outcomes included histologic assessment; changes in pain visual analog scale (VAS) score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and International Knee Documentation Committee (IKDC) score from baseline; and adverse events.

Results: Among 114 randomized participants (mean age, 55.9 years; 67% female; body mass index, 26.2 kg/m), 89 completed the phase 3 clinical trial and 73 were enrolled in the 5-year follow-up study. The mean defect size was 4.9 cm in the UCB-MSC-HA group and 4.0 cm in the microfracture group ( = .051). At 48 weeks, improvement by ≥1 ICRS grade was seen in 97.7% of the UCB-MSC-HA group versus 71.7% of the microfracture group ( = .001); the overall histologic assessment score was also superior in the UCB-MSC-HA group ( = .036). Improvement in VAS pain, WOMAC, and IKDC scores were not significantly different between the groups at 48 weeks, however the clinical results were significantly better in the UCB-MSC-HA group at 3- to 5-year follow-up ( < .05). There were no differences between the groups in adverse events.

Conclusion: In older patients with symptomatic, large, full-thickness cartilage defects with or without osteoarthritis, UCB-MSC-HA implantation resulted in improved cartilage grade at second-look arthroscopy and provided more improvement in pain and function up to 5 years compared with microfracture.

Registration: NCT01041001, NCT01626677 (ClinicalTrials.gov identifier).
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http://dx.doi.org/10.1177/2325967120973052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809531PMC
January 2021

Serum Amyloid A Is a Biomarker of Disease Activity and Health-Related Quality-of-Life in Patients with Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

Dis Markers 2020 16;2020:8847306. Epub 2020 Dec 16.

Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.

Serum amyloid A (SAA) is one of the acute phase proteins synthesized in hepatocytes and secreted by various inflammation or infectious stimuli. We investigated the clinical implication of measuring SAA in patients with antineutrophil cytoplasmic antibody- (ANCA-) associated vasculitis (AAV). Seventy-five patients who had been classified as AAV and enrolled in our prospective observational cohort for AAV patients were included. Clinical and laboratory data were obtained on the day of blood sampling, and SAA was measured by ELISA kits. Birmingham Vasculitis Activity Score (BVAS) and Short-Form 36-Item Health Survey (SF-36) were assessed for disease activity and health-related quality-of-life (HRQoL) measures. We stratified patients into having high BVAS when the BVAS was over the median values, and those with either low SF-36 PCS or low SF-36 MCS were defined as having poor HRQoL. Multivariate logistic regression analysis was conducted to estimate independent predictors of high BVAS. The relative risk (RR) was analyzed using the contingency tables and the chi-squared test. SAA was positively correlated with BVAS ( = 0.642) and FFS ( = 0.367) and was inversely correlated with both the SF-36 physical component summary ( = -0.456) and mental component summary scores ( = -0.394). Furthermore, SAA was significantly correlated with acute phase reactants ESR ( = 0.611) and CRP ( = 0.629). Patients with high BVAS exhibited significantly higher SAA than those with low BVAS (1317.1 ng/mL vs. 423.1 ng/mL). In multivariable logistic regression analysis, serum albumin (odds ratio (OR) 0.132) and SAA > 1173.6 ng/mL (OR 15.132) were independently associated with high BVAS. The risk of having high BVAS and poor HRQoL in patients with SAA > 1173.6 ng/mL was higher than in those with SAA ≤ 1173.6 ng/mL (RR 3.419 and 1.493). Our results suggest that SAA might be a useful biomarker in assessing disease activity and HRQoL in AAV.
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http://dx.doi.org/10.1155/2020/8847306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787824PMC
December 2020

Systemic inflammation response index predicts all-cause mortality in patients with antineutrophil cytoplasmic antibody-associated vasculitis.

Int Urol Nephrol 2021 Jan 11. Epub 2021 Jan 11.

Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.

Objectives: A systemic inflammation response index (SIRI) has been recently introduced as a tool for the assessment of the prognosis of several critical medical conditions. In this study, we investigated whether SIRI at diagnosis could estimate the cross-sectional disease activity and predict poor prognosis during follow-up in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).

Methods: We reviewed the medical records of 224 immunosuppressive drug-naïve AAV patients and obtained clinical and laboratory data both at diagnosis and during follow-up. SIRI was calculated using the following equation: SIRI = peripheral blood neutrophil count × monocyte count/lymphocyte count.

Results: The median age of AAV patients at diagnosis was 59.0 years and 33% were male. In the univariable linear regression analysis, SIRI value at diagnosis was not significantly correlated with the cross-sectional Birmingham vasculitis activity score (BVAS) (r = 0.125, P = 0.062). When the SIRI cut-off value at diagnosis was set at 2847.9 mm using the receiver operator characteristic curve, the sensitivity was 56.0% and the specificity was 68.3% for all-cause mortality [area 0.618, 95% confidence interval (CI) 0.502, 0.734]. AAV patients with SIRI ≥ 2847.9 mm had a significantly higher risk for all-cause mortality than those with SIRI < 2847.9 mm [relative risk (RR) 2.747, 95% CI 1.181, 6.392]. During follow-up, AAV patients with SIRI ≥ 2847.9 mm exhibited a significantly lower patients' survival rate than those with SIRI < 2847.9 mm (P = 0.003).

Conclusions: SIRI at diagnosis could predict all-cause mortality during follow-up but it could not estimate the cross-sectional BVAS in AAV patients.
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http://dx.doi.org/10.1007/s11255-020-02777-4DOI Listing
January 2021

A systematic review comparing the results of early vs delayed ligament surgeries in single anterior cruciate ligament and multiligament knee injuries.

Knee Surg Relat Res 2021 Jan 7;33(1). Epub 2021 Jan 7.

Department of Orthopedic Surgery, Centre Hospitalier de Versailles, Le Chesnay, France.

Purpose: The purpose of this study was to compare clinical outcomes and incidence of concomitant injuries in patients undergoing early vs delayed surgical treatment of single anterior cruciate ligament (ACL) injury and multiligament knee injury (MLKI).

Methods: A literature search using PubMed, Embase, the Cochrane Library, the Cumulative Index to Nursing and Allied Health, and Scopus from their inception to April 30, 2020 was conducted. Studies with levels I to IV evidence reporting the incidence of meniscus or cartilage injury according to early vs delayed surgery in single ACL injuries and MLKIs were included. In the meta-analysis, data based on the number of meniscus and cartilage injuries were extracted and pooled. Lysholm and Tegner scores were analyzed using two-sample Z-tests to calculate the non-weighted mean difference (NMD). A meta-regression analysis was also performed to determine the effect of single ACL injury and MLKI/study design.

Results: Sixteen studies on single ACL injury and 14 studies on MLKI were included in this analysis. In the analysis, there were significant decreases in Lysholm score (NMD - 5.3 [95% confidence interval (CI) - 7.37 to - 3.23]) and Tegner score (NMD - 0.25 [95% CI - 0.45 to - 0.05]) and increases in risk of meniscus tear (odds ratio [OR] 1.73 [95% CI 1.1-2.73], p = 0.01) and cartilage injury (OR 2.48 [95% CI 1.46-4.2], p = 0.0007) in the delayed surgery group regardless of single ACL injury or MLKI. The result of the meta-regression analysis indicated that single ACL injury and MLKI/study design were not significant moderators of overall heterogeneity (p > 0.05).

Conclusions: Our study suggests that delayed ACL surgery significantly resulted in a higher risk of meniscus tear and cartilage injury and decreased Lysholm and Tegner scores compared to early ACL surgery. The Lysholm scores in the delayed MLKI surgery group were significantly decreased, but the risks of meniscus tear and cartilage injury in the delayed MLKI surgery group remained unclear.

Level Of Evidence: Level III, meta-analysis.
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http://dx.doi.org/10.1186/s43019-020-00086-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7792064PMC
January 2021

Editorial Commentary: Stem Cell Therapy for the Knee: Heterogeneity in Cell Sources, Delivery Methods, and Concomitant Surgery Needs to Be Considered.

Authors:
Yong-Beom Park

Arthroscopy 2021 01;37(1):379-380

Chung-Ang University College of Medicine.

Mesenchymal stem cells (MSCs) have been investigated for the treatment of knee osteoarthritis because of their unique properties, including self-renewal, multi-linear cellular differentiation, and immunomodulatory capacity. However, the efficacy of MSCs for positive clinical outcomes in the treatment of knee osteoarthritis remains controversial. Because clinical studies in general have high variability, the heterogeneity in the sources of the stem cells used, efficacy of delivery methods, and concomitant surgery should be carefully considered to interpret the benefits of MSC therapy for knee osteoarthritis.
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http://dx.doi.org/10.1016/j.arthro.2020.07.035DOI Listing
January 2021

Editorial Commentary: Stem Cell Treatment in Knee Osteoarthritis: What for? Pain Management or Cartilage Regeneration?

Arthroscopy 2021 01;37(1):359-361

Chung-Ang University.

The efficacy of mesenchymal stem cells regarding clinical outcomes and cartilage regeneration in knee osteoarthritis remains unclear; however, their theoretical role in multilineage cellular differentiation and immunomodulation of the arthritic cascade has been investigated. Several studies have reported that the use of stem cell therapy for knee osteoarthritis helps in pain improvement, but its effect on cartilage regeneration has not yet been explored. Moreover, numerous studies have reported high heterogeneity in the cell sources, as well as methods of culture expansion or cell concentration, and differences in delivery methods, assessment tools, and concomitant surgical procedures, which could affect the clinical outcomes or evaluation of cartilage regeneration potency. Furthermore, future studies are warranted to examine these factors in detail to interpret the results of mesenchymal stem cell treatment for knee osteoarthritis.
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http://dx.doi.org/10.1016/j.arthro.2020.11.017DOI Listing
January 2021

Drug Survival of Biologic Therapy in Elderly Patients With Rheumatoid Arthritis Compared With Nonelderly Patients: Results From the Korean College of Rheumatology Biologics Registry.

J Clin Rheumatol 2020 Dec 14;Publish Ahead of Print. Epub 2020 Dec 14.

From the Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine Division of Rheumatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea.

Objective: Although the proportion of elderly patients with rheumatoid arthritis (RA) is increasing, the persistency of biologic therapy in elderly patients requires additional investigation. This study evaluated the drug survival of biologic therapy and associated factors in elderly compared with nonelderly patients.

Methods: This longitudinal observational study included RA patients who were enrolled in the Korean College of Rheumatology Biologics Registry (NCT01965132, started from January 1, 2013) between 2013 and 2015. We compared the retention rate of biologic therapy between elderly (age ≥70 years) and nonelderly (age <70 years) patients, and investigated the causes and predictors of biologic withdrawal in both groups.

Results: Of 682 patients, 122 were aged 70 years or older. The retention rate of biologic therapy at 24 months was 57.8% and 46.5% in nonelderly and elderly patients, respectively (p = 0.027). Biologic withdrawal due to adverse events and inefficacy within 24 months was not significantly different between the 2 groups, although adverse events were more common in elderly patients (20.6% vs 12.8%, p = 0.360). Drug withdrawal due to patient refusal was more common in elderly patients (9.8% vs 1.8%, p < 0.001). In elderly patients, biologic withdrawal was associated with current smoking and older age at disease onset, whereas the use of tumor necrosis factor inhibitors, nonuse of methotrexate, and combination of corticosteroid were important in nonelderly patients.

Conclusions: Elderly RA patients are more likely to discontinue biologic agents within 24 months. To increase the retention rate of biologic therapy, rheumatologists should consider patient characteristics before and during biologic therapy.
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http://dx.doi.org/10.1097/RHU.0000000000001644DOI Listing
December 2020

Efficacy of the fibrosis index for predicting end-stage renal disease in patients with antineutrophil cytoplasmic antibody-associated vasculitis.

Int J Clin Pract 2020 Dec 10:e13929. Epub 2020 Dec 10.

Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.

Objective: Kidney involvement is a major manifestation of antineutrophil cytoplasmic antibody-associated vasculitis (AAV) and may progress to end-stage renal disease (ESRD), requiring renal replacement therapy. Unfortunately, there is no reliable kidney-specific index for predicting the progression of renal disease to ESRD. The fibrosis index (FI) reflects the degree of fibrosis in chronic liver disease. This study aimed to investigate whether the FI at the time of diagnosis could predict the development of ESRD in AAV patients.

Methods: We retrospectively reviewed the medical records of 211 immunosuppressive drug-naïve AAV patients and extrapolated the cut-off FI value for predicting the development of ESRD using receiver operating characteristic curves. The associations between the FI and clinical outcomes, including mortality, relapse, and ESRD development, were determined.

Results: Overall, 39 (18.5%) patients developed ESRD owing to the progression of AAV-associated renal disease. The median FI was higher in AAV patients with ESRD than in those without (1.61 vs 1.04; P = .001). The FI cut-off was 1.72. The incidence of ESRD was higher in patients with FI ≥ 1.72 at the time of diagnosis than in those with an FI < 1.72 at the time of diagnosis (relative risk: 4.655; 95% confidence interval: 2.242-9.662; P < .001). Kaplan-Meier survival analysis revealed that patients with an FI ≥ 1.72 at the time of diagnosis exhibited significantly lower ESRD-free survival rates than those with an FI < 1.72 at the time of diagnosis (P < .001).

Conclusion: FI ≥ 1.72 at the time of diagnosis may be an independent predictive marker for ESRD in AAV patients.
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http://dx.doi.org/10.1111/ijcp.13929DOI Listing
December 2020

Meta-analysis of 208370 East Asians identifies 113 susceptibility loci for systemic lupus erythematosus.

Ann Rheum Dis 2020 Dec 3. Epub 2020 Dec 3.

Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea

Objective: Systemic lupus erythematosus (SLE), an autoimmune disorder, has been associated with nearly 100 susceptibility loci. Nevertheless, these loci only partially explain SLE heritability and their putative causal variants are rarely prioritised, which make challenging to elucidate disease biology. To detect new SLE loci and causal variants, we performed the largest genome-wide meta-analysis for SLE in East Asian populations.

Methods: We newly genotyped 10 029 SLE cases and 180 167 controls and subsequently meta-analysed them jointly with 3348 SLE cases and 14 826 controls from published studies in East Asians. We further applied a Bayesian statistical approach to localise the putative causal variants for SLE associations.

Results: We identified 113 genetic regions including 46 novel loci at genome-wide significance (p<5×10). Conditional analysis detected 233 association signals within these loci, which suggest widespread allelic heterogeneity. We detected genome-wide associations at six new missense variants. Bayesian statistical fine-mapping analysis prioritised the putative causal variants to a small set of variants (95% credible set size ≤10) for 28 association signals. We identified 110 putative causal variants with posterior probabilities ≥0.1 for 57 SLE loci, among which we prioritised 10 most likely putative causal variants (posterior probability ≥0.8). Linkage disequilibrium score regression detected genetic correlations for SLE with albumin/globulin ratio (r=-0.242) and non-albumin protein (r=0.238).

Conclusion: This study reiterates the power of large-scale genome-wide meta-analysis for novel genetic discovery. These findings shed light on genetic and biological understandings of SLE.
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http://dx.doi.org/10.1136/annrheumdis-2020-219209DOI Listing
December 2020

Computed Tomography Detects Hinge Fractures After Medial Opening Wedge High Tibial Osteotomy: A Systematic Review.

Arthroscopy 2020 Nov 23. Epub 2020 Nov 23.

Department of Orthopedic Surgery, Chung-Ang University Hospital, Chung-Ang University, Seoul, Republic of Korea. Electronic address:

Purpose: To quantify the increased detection rate of lateral hinge fractures (LHFs) owing to additional computed tomography (CT), determine factors associated with LHFs, and compare radiologic and clinical outcomes of LHFs after medial opening wedge biplanar high tibial osteotomy (MOW-HTO).

Methods: The MEDLINE, Embase, Cochrane Library, and Web of Science databases were systematically searched to identify studies reporting the incidence of LHFs detected using additional CT, showing radiologic factors, or comparing radiologic and clinical outcomes between LHFs and non-LHFs after MOW-HTO. Subgroup analyses were performed to compare stable and unstable LHFs. Two reviewers performed the study screening, risk-of-bias assessment, and data extraction processes.

Results: Eleven studies were included in this review. The weighted estimate of the apparent incidence of LHFs in the pooled studies was 24.8%. The weighted estimate of the incidence was increased by 9.9% owing to the use of CT detection, which indicated that approximately 40% of total diagnosed LHFs were missed on plain radiographs or fluoroscopy. The pooled mean opening gap distance ranged from 11.40 to 12.60 mm in the LHF group and from 9.80 to 11.12 mm in the non-LHF group, and the mean difference in the opening gap distance was significantly larger in the LHF group (95% confidence interval, 0.64-1.84 mm; P < .0001). However, no significant differences in correction loss, bone union duration, and clinical outcomes were observed between the LHF and non-LHF groups. Subgroup analyses showed no significant differences between stable and unstable LHFs.

Conclusions: Postoperative CT evaluations increase the detection rate of LHFs compared with plain radiography alone. Furthermore, the opening gap distance was larger in the LHF group than in the non-LHF group, suggesting the need for attention when opening the wedge by more than 11.4 mm. However, the consequences of LHFs after MOW-HTO were not major concerns when proper management was provided.

Level Of Evidence: Level III, systematic review.
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http://dx.doi.org/10.1016/j.arthro.2020.11.031DOI Listing
November 2020

Pan-immune-inflammation value at diagnosis independently predicts all-cause mortality in patients with antineutrophil cytoplasmic antibody-associated vasculitis.

Clin Exp Rheumatol 2020 Nov 10. Epub 2020 Nov 10.

Division of Rheumatology, Department of Internal Medicine and Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, Republic of Korea.

Objectives: The pan-immune-inflammation value (PIIV), a novel, validated predictor of the prognosis of several diseases, has been recently introduced. We investigated whether PIIV at diagnosis could predict all-cause mortality during follow-up in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).

Methods: Medical records of 219 immunosuppressive drug-naïve patients with AAV were reviewed. PIIV was calculated as follows: neutrophil count (x 1000/m3) x monocyte count (x 1000/m3) x platelet count (x 1000/mm3) / lymphocyte count (x 1000/m3). Additionally, conventional risk factors of mortality, AAV-specific indices, and acute-phase reactants at diagnosis were evaluated.

Results: The median age at diagnosis was 59.0 years and 32.9% of the patients were male. During follow-up, 24 patients (11.0%) died due to all causes. When the cut-off of PIIV at diagnosis for all-cause mortality was set at 1011.3, sensitivity and specificity of 52.0% and 71.2%, were attained (p=0.041). When AAV patients were divided into two groups according to the calculated cut-off, those with PIIV ≥1011.3 at diagnosis had a significantly lower cumulative survival rate than those without (p=0.009). In the multivariable Cox hazards model analysis, male gender (HR 2.307), FFS (HR 1.728) and PIIV ≥1011.3 (HR 2.689) were identified as significant and independent risk factors of all-cause mortality.

Conclusions: PIIV at diagnosis exceeding the optimal cut-off for death could predict all-cause mortality during follow-up in AAV patients comparable to male gender and FFS at diagnosis.
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November 2020

Incidence of Tuberculosis in Systemic Necrotizing Vasculitides: A Population-Based Study From an Intermediate-Burden Country.

Front Med (Lausanne) 2020 22;7:550004. Epub 2020 Oct 22.

Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.

Tuberculosis (TB) has a significant impact on public health; however, its incidence in patients with systemic necrotizing vasculitides (SNV) remains unknown. Therefore, we evaluated the incidence of TB in patients with SNV using a nationwide claims database. The Health Insurance and Review Agency database was used to identify patients diagnosed with SNV between 2010 and 2018. The standardized incidence ratio (SIR) was calculated to compared the risk of TB between patients and the general population, based on the 2016 annual national TB report. The incidence of TB after SNV diagnosis was compared by estimating age- and sex- adjusted incidence rate ratio (IRR). A time-dependent Cox regression analysis was performed to estimate factors associated with TB. Among the included 2,660 patients, 51 (1.9%) developed TB during the follow-up period. The risk of TB was significantly higher in patients with SNV [SIR 6.09, 95% confidence interval (CI) 4.53-8.00], both in men (SIR 5.95) and women (SIR 6.26), than in the general population; this increased risk was consistent in all disease subtypes, except eosinophilic granulomatosis with polyangiitis. Additionally, the incidence of TB was the highest in patients with SNV within the first 3 months after diagnosis (adjusted IRR: 8.90 compared to TB ≥ 12 months). In Cox regression analysis, the diagnosis of microscopic polyangiitis [hazard ratio (HR) 3.22, 95% CI 1.04-9.99], granulomatosis with polyangiitis (HR 4.63, 95% CI 1.53-14.02), and polyarteritis nodosa (HR 3.51, 95% CI 1.13-10.88) were independent factors associated with TB. Even when considering the high incidence of TB in the geographic region, the risk of TB increased in patients with SNV, with a difference based on disease subtypes. Moreover, taking into account of the high incidence of TB in SNV, vigilant monitoring for TB is required especially during the early disease period.
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http://dx.doi.org/10.3389/fmed.2020.550004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7649822PMC
October 2020

Serum granzyme B is associated with otorhinolaryngological, pulmonary, and renal involvement of antineutrophil cytoplasmic antibody-associated vasculitis.

J Investig Med 2021 Jan 12;69(1):91-95. Epub 2020 Nov 12.

Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea (the Republic of)

We investigated whether serum granzyme B (GrB) can reflect the inflammatory burden such as cross-sectional disease activity and organ-specific involvement in immunosuppressive drug-naïve patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Seventy-eight immunosuppressive drug-naïve patients with AAV were included in this study. At the time of the first classification, whole blood was obtained from each patient and sera was immediately isolated and stored at - 80℃. On the day of the blood sampling, we performed routine laboratory tests including antineutrophil cytoplasmic antibody tests and collected both clinical and laboratory data. AAV-specific indices included Birmingham Vasculitis Activity Score (BVAS) and Five-Factor Score (FFS). The median age of patients with AAV was 62 years and 26 patients were men. Serum GrB was not associated with the cross-sectional BVAS; however, patients with serum GrB positivity exhibited higher frequencies of otorhinolaryngological manifestation than those without (p=0.037). When serum GrB levels were compared after dividing the patients into two groups based on the presence of organ-specific involvement, patients with pulmonary involvement exhibited a significantly higher serum GrB than those without (p=0.042). On the other hand, patients with renal involvement showed a significantly lower serum GrB than those without (p=0.023). In addition, serum GrB was inversely correlated with the cross-sectional FFS (r=-0.249, p=0.028). Even though serum GrB could not reflect the inflammatory burden of AAV, serum GrB was associated with otorhinolaryngological, pulmonary, and renal involvement in immunosuppressive drug-naïve patients with AAV.
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http://dx.doi.org/10.1136/jim-2020-001365DOI Listing
January 2021

Pregnancy Morbidities in Korean Patients with Takayasu Arteritis: A Monocentric Pilot Study.

Yonsei Med J 2020 Nov;61(11):970-975

Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.

We investigated pregnancy morbidities in Korean patients with Takayasu arteritis (TA) in a single tertiary hospital as a pilot study. We retrospectively reviewed the medical records of 12 pregnancies in seven patients with TA. All patients were diagnosed with TA based on the 1990 American College of Rheumatology classification criteria. The medical records of patients were well-documented, allowing review of clinical data including pregnancy morbidities. The angiographic and Ishikawa classifications at diagnosis and TA activity at delivery were assessed. Of the 12 pregnancies, two pregnancies ended in spontaneous abortion (16.7%), and one pregnancy (8.3%) had therapeutic abortion at 9 weeks due to maternal morbidity. Among the remaining nine pregnancies, only one child was delivered via normal spontaneous vaginal delivery, and the remaining eight were delivered by Caesarean section. Two out of nine (22.2%) neonates were born with low birth weight, and one of them was born at 30 weeks of gestation. The most common maternal complication was hypertension affecting 7/12 (58.3%) pregnancies. Preeclampsia occurred in one pregnancy, and gestational diabetes mellitus (GDM) occurred in two pregnancies. At delivery, disease activity of TA was stable in all pregnancies, and glucocorticoids were administered in nine pregnancies. Live birth rate of pregnant Korean patients with TA was 75%. Future studies are needed to reduce pregnancy-related complications.
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http://dx.doi.org/10.3349/ymj.2020.61.11.970DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7593103PMC
November 2020

Worse Renal Presentation and Prognosis in Initial-Onset Lupus Nephritis than Early-Onset Lupus Nephritis.

Yonsei Med J 2020 Nov;61(11):951-957

Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.

Purpose: To compare the clinical characteristics and renal outcomes between patients who initially had lupus nephritis (LN) at the onset of systemic lupus erythematosus (SLE) (initial-onset LN) and those who developed LN within 5 years after SLE onset (early-onset LN).

Materials And Methods: SLE patients with biopsy-proven LN were retrospectively reviewed. The clinical parameters and renal outcomes were compared between initial-onset and early-onset LN groups. We used Cox regression analysis to estimate risk of worse renal outcomes according to the onset time of LN.

Results: Of all 136 LN patients, 92 (67.6%) and 44 (32.4%) patients were classified into the initial-onset and early-onset LN groups, respectively. The initial-onset LN group had higher prevalences of class IV LN (54.3% vs. 34.1%, =0.027), impaired renal function (34.8% vs. 11.4%, =0.004), microscopic hematuria (73.9% vs. 54.5%, =0.024), and higher urine protein/creatinine ratio [4626.1 (2180.0-6788.3) mg/g vs. 2410.0 (1265.0-5168.5) mg/g, =0.006] at LN diagnosis. Renal relapse (46.3% vs. 25.7%, =0.039) and progression to chronic kidney disease (CKD) or end-stage renal disease (ESRD) were more common (24.4% vs. 8.3%, =0.042) in the initial-onset LN group. In Cox regression analysis, the initial-onset LN group had higher risks of renal relapse [adjusted hazard ratio (HR) 3.56, 95% confidence interval (CI) 1.51-8.35, =0.004] and progression to CKD or ESRD (adjusted HR 4.57, 95% CI 1.03-20.17, =0.045), compared with the early-onset LN group.

Conclusion: Patients with LN at SLE onset may have more severe renal presentations and experience worse renal outcomes than those who develop LN within 5 years.
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http://dx.doi.org/10.3349/ymj.2020.61.11.951DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7593100PMC
November 2020

A new index for distinguishing hypereosinophilic syndrome and antineutrophil cytoplasmic antibody-negative eosinophilic granulomatosis with polyangiitis.

Asian Pac J Allergy Immunol 2020 Oct 17. Epub 2020 Oct 17.

Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.

Background: It is difficult to differentiate between hypereosinophilic syndrome (HES) and antineutrophil cytoplasmic antibody (ANCA)-negative eosinophilic granulomatosis with polyangiitis (EGPA).

Objective: We compared laboratory data at diagnosis between Korean patients with HES and ANCA-negative EGPA and investigated independent laboratory predictors suggesting HES.

Methods: We reviewed the medical records of 41 HES patients and 16 ANCA-negative EGPA patients. The cut-offs were extrapolated by the receiver operator characteristic (ROC) curve. The odds ratio (OR) and relative risk (RR) were assessed using the multivariable logistic regression analysis and the chi-square test, respectively. We developed a new equation by assigning a weight to each variable according to the slopes (B) and expressed a decimal as the nearest integer.

Results: HES patients had a higher median WBC and eosinophil counts than ANCA-negative EGPA patients. The cutoffs of WBC and eosinophil counts for HES were set at 9,900.0/mm3 and 2,400.0/mm3. In the multivariable analysis, WBC count ≥ 9,900.0/mm3 (B 1.763) and eosinophil count ≥ 2,400.0/mm3 (B 1.515) were significantly associated with HES. An equation was as follows: HES-suggesting laboratory index (HSLI) = 2 × (WBC count ≥ 9,900.0/mm3 (1 = No or 2 = Yes)) + 1.5 × (eosinophil count ≥ 2,400.0/mm3 (1 = No or 2 = Yes)). The cut-off of HSLI for HES was 4.25. Patients with HSLI ≥ 4.25 exhibited a significantly high RR (51.429) for HES, compared to those without.

Conclusions: In conclusion, the cut-off of HSLI derived from WBC and eosinophil counts could be an independent predictor of HES in patients suspected of both HES and ANCA-negative EGPA.
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http://dx.doi.org/10.12932/AP-080420-0805DOI Listing
October 2020

Efficacy and Safety of Rituximab in Korean Patients with Refractory Inflammatory Myopathies.

J Korean Med Sci 2020 Sep 28;35(38):e335. Epub 2020 Sep 28.

Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea.

Background: Rituximab (RTX), a monoclonal antibody that selectively binds to CD20+ B cells, showed favorable outcomes in patients with idiopathic inflammatory myopathies (IIM) in small case series, but the evidence is still not enough. Our goal was to determine the efficacy and safety of RTX for Korean patients with refractory IIM.

Methods: We retrospectively analyzed the medical records of 16 patients with refractory IIM treated with RTX in seven tertiary rheumatology clinics in the Korea. The efficacy of RTX was evaluated with the improvement of serum creatine phosphokinase (CPK) level and physician's global assessment (PGA), and daily corticosteroid dose reduction. A > 25% decrease in CPK level, corticosteroid dose, or PGA was considered significant. A complete response (CR) was designated by meeting three efficacy criteria and a partial response (PR) by only two criteria.

Results: Sixteen patients with IIM were evaluated (13 female; median age, 51.8 years). All patients had received at least one conventional immunosuppressive agent (median, 3.6 [2.0-5.0]) and concomitant corticosteroids. The median CPK level and median dose of prednisolone was 421.0 units/L and 20.0 mg/day respectively. Eleven patients were treated with intravenous immunoglobulin. Seven patients received 2,000 mg of RTX and the others received lower dose. Twenty-four weeks after RTX treatment, 11 patients achieved a > 25% reduction in corticosteroid dose and CPK levels, and nine showed improved PGA. The overall response rate was 68.8% (11 patients). At the end of follow-up (median 24 weeks), 12 (75.0%) patients responded overall: four (25.0%) and eight (50.0%) patients achieved CR and PR, respectively. Baseline muscle enzyme levels were higher in responders than non-responders, but disease duration, RTX dose, ESR and serum CRP were not significantly different between the two groups. The rate of adverse event was 25.4/1,000 person-years.

Conclusion: RTX could be an effective and relatively safe therapeutic option in patients with refractory IIM.
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http://dx.doi.org/10.3346/jkms.2020.35.e335DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521958PMC
September 2020

Clinical and imaging findings suggestive of histopathological immunoglobulin G4-related disease: a single-center retrospective study.

Clin Rheumatol 2020 Aug 28. Epub 2020 Aug 28.

Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, Republic of Korea.

Objective: To investigate the clinical and imaging features predicting the histopathological diagnosis of immunoglobulin G4 (IgG4)-related disease (IgG4RD) in patients with suspected IgG4RD on computed tomography (CT).

Methods: We retrospectively reviewed the medical records of 178 patients with CT findings suspicious of IgG4RD from January 2015 to December 2017. Patients who underwent tissue biopsy were included to evaluate the association between patient characteristics and histopathological diagnosis of IgG4RD. The histopathological diagnosis was classified into IgG4RD and non-IgG4RD. Clinical, laboratory, and imaging features were compared between patients with IgG4RD and non-IgG4RD, and logistic regression analysis was performed to identify the predictors for histopathologically confirmed IgG4RD.

Results: Of the 103 patients with histopathologically proven diseases, 46 and 57 patients were classified as IgG4RD and non-IgG4RD, respectively. The median age was 64 years; 65% of patients were male. There were significant differences in sex (P = 0.035), fever (P = 0.039), serum IgG4 level (P < 0.001), renal involvement (P = 0.036), lacrimal or salivary glands involvement (P = 0.050), swelling pattern on CT (P = 0.001), and positron emission tomography (PET)-CT findings (P < 0.001) between patients with IgG4RD and non-IgG4RD. Multivariate analysis revealed elevated IgG4 level > 135 mg/dL (odds ratio [OR] = 5.418, P < 0.001), kidney involvement (OR = 6.170, P = 0.044), and the swelling feature on CT (OR = 4.301, P = 0.012) to be independent factors for histopathological diagnosis of IgG4RD.

Conclusion: This study suggests that elevated IgG4 level, renal involvement, and swelling pattern on CT are associated with histopathological diagnosis of IgG4RD. The clinical and imaging features might help to decide further evaluation in patients with clinically suspected IgG4RD. Key Points • Computed tomography (CT) is not sufficient to discriminate between IgG4-related disease (IgG4RD) and non-IgG4RD conditions. • Histopathological diagnosis of IgG4RD is associated with elevated IgG4 level, renal involvement, and swelling pattern on CT. • Positron emission tomography-CT may be a useful diagnostic tool in patients with clinically suspected IgG4RD. >.
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http://dx.doi.org/10.1007/s10067-020-05366-zDOI Listing
August 2020

Total Knee Arthroplasty after Previous Ipsilateral Hip Arthroplasty Showed Lower Clinical Outcomes and Higher Leg Length Discrepancy Perception.

J Knee Surg 2020 Aug 24. Epub 2020 Aug 24.

Department of Orthopedic Surgery, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Dongjak-gu, Seoul, South Korea.

The purpose of this study is to compare perception of leg length discrepancy (LLD) and clinical results of total knee arthroplasties (TKA) in patients with or without previous ipsilateral hip arthroplasty. Between 2008 and 2015, navigation-assisted TKA was performed in 43 patients with previous hip arthroplasty after hip fracture. After 1:3 propensity score matching was performed, 108 patients of primary navigation-assisted TKA (group 1) and 36 patients with hip arthroplasty (group 2) were included. Knee Society (KS) scores, Western Ontario and McMaster Universities Index (WOMAC) scores, and patients' satisfaction including perception of LLD were evaluated. Radiographic evaluation included mechanical axis, component position, and LLD. Logistic regression analysis was performed to find the factors that affect the clinical outcomes. No significant differences in radiologic and clinical evaluations, except for KS function score, patient's satisfaction and LLD (< 0.001), were detected between the groups. LLD and its perception were significantly higher in group 2 (1.8 ± 3.4 mm in group 1 and 9.7 ± 4.1 mm in group 2,  = 0.000). Risk factors for the low KS function score were found as LLD (odds ratio [OR]: 1.403,  = 0.008) and previous hip arthroplasty itself (OR: 15.755,  = 0.002), but much higher OR was found in previous hip arthroplasty. Although the outcomes of TKA in patients with ipsilateral hip arthroplasty are comparable to those of primary TKA, LLD was high and patient's satisfaction and functional outcomes were low in patients with previous ipsilateral hip arthroplasty. Care should be taken when considering TKA in patients with previous hip arthroplasty. This is a Level III, case control study.
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http://dx.doi.org/10.1055/s-0040-1715447DOI Listing
August 2020

Clinical features of Korean elderly patients with antineutrophil cytoplasmic antibody-associated vasculitis.

Korean J Intern Med 2020 Aug 20. Epub 2020 Aug 20.

Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.

Background/aims: We compared the clinical and laboratory data between elderly and non-elderly patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) at diagnosis; further, we investigated the predictors at diagnosis for all-cause mortality and end-stage renal disease (ESRD) occurrence during follow-up in Korean elderly patients with AAV.

Methods: We reviewed the medical records of 191 AAV patients regarding clinical manifestations and laboratory results at diagnosis and during follow-up. The follow-up duration was defined as the period from diagnosis to death for deceased patients or to the time of dialysis for ESRD patients, or to the last visit. Elderly (n = 67) and non-elderly (n = 124) patients were grouped based on an age threshold of 65 years.

Results: At diagnosis, elderly patients exhibited higher median Birmingham Vasculitis Activity Score (BVAS) and higher frequencies of ANCA positivity and pulmonary manifestations than non-elderly patients. Furthermore, elderly patients exhibited increased median white blood cell count, blood urea nitrogen (BUN), alkaline phosphatase, erythrocyte sedimentation rate, and C-reactive protein and decreased median hemoglobin. However, there were no significant differences in all-cause mortality and ESRD occurrence between elderly and non-elderly patients. Meanwhile, elderly patients exhibited lower cumulative patients' and ESRD-free survival rates than non-elderly patients. In the multivariable Cox hazards model, BUN, creatinine and serum albumin at diagnosis were independent predictors for ESRD occurrence, whereas there were no independent predictors at diagnosis for all-cause mortality.

Conclusions: Elderly AAV patients exhibited substantially higher rates of all-cause mortality and ESRD occurrence during follow-up compared than non-elderly AAV patients.
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http://dx.doi.org/10.3904/kjim.2020.039DOI Listing
August 2020

Evaluation of body composition using computed tomography in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis.

Korean J Intern Med 2020 Aug 18. Epub 2020 Aug 18.

Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.

Background/aims: Measures of body composition, including visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and skeletal muscle area (SMA), are considered important prognostic factors in chronic diseases. The association of these measures with auto-inflammatory disorders, such as anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV), remains unclear. We investigated the clinical significance of VAT, SAT, and SMA in patients with AAV.

Methods: Patients with AAV subjected to chest computed tomography (CT), abdominal CT, or positron emission tomography-CT on diagnosis of AAV were evaluated. Quantitative assessment of VAT, SAT, and SMA was performed at the third lumbar vertebral level and computed by summing the pixel attenuation for tissue-specific Hounsfield units in the corresponding region. Associations of VAT, SAT, and SMA with clinical and laboratory data and clinical outcome measures were evaluated.

Results: Of the 117 patients, 61 (52.1%) were classified as having microscopic polyangiitis, 28 (23.9%) as granulomatosis with polyangiitis, and 28 (23.9%) as eosinophilic granulomatosis with polyangiitis. VAT significantly correlated with age, weight, body mass index (BMI), and Birmingham Vasculitis Activity Score, whereas SAT correlated with weight, BMI, and creatinine levels. A significant association was found between SMA and age, height, weight, BMI, and the Five-Factor Score. Cox proportional hazards analysis showed that creatinine levels (odds ratio [OR], 1.346; 95% confidence interval [CI], 1.034 to 1.753; p = 0.027) and high VAT (OR, 7.137; 95% CI, 1.343-37.946; p = 0.021) were independently associated with all-cause mortality during follow-up.

Conclusions: Evaluation of VAT using CT is useful for estimating disease activity and all-cause mortality in patients with AAV.
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http://dx.doi.org/10.3904/kjim.2020.064DOI Listing
August 2020

Atherogenic index of plasma predicts cerebrovascular accident occurrence in antineutrophil cytoplasmic antibody-associated vasculitis.

Lipids Health Dis 2020 Aug 14;19(1):184. Epub 2020 Aug 14.

Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, Republic of Korea, 03722.

Background: To investigate whether atherogenic index of plasma (AIP) at diagnosis is associated with the occurrence of cerebrovascular accident (CVA) or coronary artery disease (CAD) in antineutrophil cytoplasmic antibody-associated vasculitis (AAV).

Methods: The medical records of 167 AAV patients on initial diagnosis was reviewed, and 300 healthy controls were included. AIP was calculated using the following equation: AIP = Log (triglyceride [mg/dL] / high-density lipoprotein cholesterol [mg/dL]). AAV patients were divided into two groups according to the AIP cut-off of 0.11. The event of stroke, transient ischemic attack, and cerebral hemorrhage was recorded as CVA, and CAD events consisted of either myocardial infarction and angina pectoris. CVA- and CAD- free survival rate between those with AIP ≥ 0.11 and < 0.11 were compared by the Kaplan-Meier analysis, and Cox hazard analysis was conducted to identify predictors of CVA.

Results: The median age of AAV patients were 59.0 years, and 54 (32.3%) patients were male. One-hundred and fifteen (68.9%) patients had AIP < 0.11 and 52 (31.1%) had AIP ≥ 0.11. The mean Birmingham vasculitis activity score in AAV patients with AIP < 0.11 was lower than that seen in patients with AIP ≥ 0.11 (12.0 vs. 14.0, P = 0.041). AAV patients had a significantly higher AIP compared to controls (mean - 0.01 vs. -0.10, P < 0.001). During follow-up, the occurrence of CVA and CAD was observed in 16 (9.6%) and 14 (8.4%) patients, respectively. In Kaplan-Meier analysis, AAV patients with AIP ≥ 0.11 had significantly lower CVA-free survival rates than in those with AIP < 0.11 (P = 0.027), whereas there was no difference in CAD according to AIP (P = 0.390). Multivariable Cox analysis indicated that AIP ≥ 0.11 at diagnosis was the sole predictor of CVA (Hazard ratio 3.392, 95% confidence interval 1.076, 10.696, P = 0.037).

Conclusions: AIP is significantly higher in AAV patients than in healthy controls, and AIP ≥ 0.11 at diagnosis is a significant predictor of CVA during follow-up. Stringent surveillance should be provided in AAV patients with AIP ≥ 0.11 regarding the occurrence of CVA.

Trial Registration: Retrospectively registered (4-2017-0673).
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http://dx.doi.org/10.1186/s12944-020-01360-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7429760PMC
August 2020

Disease-specific factors associated with cardiovascular events in patients with Takayasu arteritis.

Arthritis Res Ther 2020 07 31;22(1):180. Epub 2020 Jul 31.

Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.

Background: To identify disease-specific factors associated with cardiovascular events in patients with Takayasu arteritis (TAK).

Methods: Patients with TAK who fulfilled the American College of Rheumatology 1990 criteria for the classification of TAK and were followed up between 2006 and 2019 were included. Traditional cardiovascular risk factors and TAK disease-specific factors at the index date and incident cardiovascular events during the follow-up were retrospectively assessed. To estimate the risk of cardiovascular events according to TAK disease-specific factors, Cox regression analysis with adjustment for traditional cardiovascular risk factors was performed.

Results: Of the total 207 patients with TAK, cardiovascular events occurred in 41 (19.8%) patients. Compared with patients who did not develop cardiovascular events, patients who developed cardiovascular events were older (38.5 ± 13.4 years vs. 43.6 ± 11.8 years, p = 0.028), more commonly had diabetes mellitus (6.6% vs. 19.5%, p = 0.029), had lower high-density lipoprotein cholesterol (57.3 ± 17.1 mg/dl vs. 51.2 ± 15.7 mg/dl, p = 0.040), more commonly had type V vascular involvement (33.1% vs. 63.4%, p 0.001), and less commonly received methotrexate (65.1% vs. 43.9%, p = 0.013). In Cox regression analysis, type V vascular involvement was significantly associated with increased risk of cardiovascular events (adjusted HR 2.852, 95% CI 1.474-5.518, p = 0.002), whereas the use of methotrexate was associated with reduced risk of cardiovascular events (adjusted HR 0.515, 95% CI 0.268-0.993, p = 0.047).

Conclusion: Type V vascular involvement was associated with increased risk of cardiovascular events, while the use of methotrexate was associated with reduced risk of cardiovascular events, in patients with TAK.
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http://dx.doi.org/10.1186/s13075-020-02275-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7395382PMC
July 2020