Publications by authors named "Yong Beom Park"

300 Publications

Clinical significance of large unstained cell count in estimating the current activity of ANCA-associated vasculitis.

Int J Clin Pract 2021 Jun 12:e14512. Epub 2021 Jun 12.

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

Background: We investigated whether large unstained cell (LUC) count could estimate the current high activity according to Birmingham vasculitis activity score (BVAS) in patients with antineutrophil cytoplasmic antibody (ANCA) positive ANCA-associated vasculitis (AAV).

Methods: We retrospectively reviewed the medical records of 176 immunosuppressive drug-naïve patients with ANCA positive AAV. Clinical and laboratory data at diagnosis, including LUC count, were collected. High BVAS was defined as the highest tertile of BVAS (BVAS ≥ 15) in this study.

Results: The median age was 61.0 years and 64.8% were female. The median LUC count was 60.0/mm and LUC was detected in 106 patients. LUC count was significantly correlated with BVAS, age, white blood cell count, haemoglobin, platelet count, serum albumin, erythrocyte sedimentation rate and C-reactive protein. Overall, the median BVAS in AAV patients with LUC positivity was significantly higher than that in those without (14.0 vs. 10.0). When the cut-off of LUC count for the current high BVAS was set as BVAS ≥ 15/mm , AAV patients with LUC count ≥ 15/mm had a significantly higher risk for the current high BVAS than those with LUC count < 15/mm (relative risk 2.596). However, in the multivariable linear and logistic regression analyses, LUC did not seem to estimate the current BVAS independently among clinical and laboratory variables.

Conclusion: LUC count was significantly correlated with the current BVAS and LUC count ≥ 15/mm could estimate the current high BVAS in patients with ANCA positive AAV.
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http://dx.doi.org/10.1111/ijcp.14512DOI Listing
June 2021

Increased prevalence rate of metabolic syndrome is an independent predictor of cardiovascular disease in patients with antineutrophil cytoplasmic antibody-associated vasculitis.

Rheumatol Int 2021 Jun 4. Epub 2021 Jun 4.

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

Objective: We investigated the prevalence of metabolic syndrome (MetS) in all or nonobese patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and compared it with age- and gender-matched controls. Also, we assessed the effect of variables at diagnosis on the risk of cardiovascular disease (CVD) in all or nonobese AAV patients.

Methods: In this study, 173 AAV patients and 344 controls were included and MetS was defined by the National Cholesterol Education Program Adults Treatment Panel III criteria. The obesity based on body mass index (BMI) was defined as BMI ≥ 25 kg/m. The follow-up duration was defined as the period from diagnosis to the last visit or to each poor outcome occurrence.

Results: The median age of AAV patients was 58.7 years and 57 patients were men. The prevalence of MetS was 50.9% in all AAV patients and 46.5% in nonobese AAV patients, which were significantly higher than 37.8% in all controls and 28.2% in nonobese controls. In Kaplan-Meier survival analysis, Mets at diagnosis significantly reduced the cumulative CVD-free survival rate in both all and nonobese AAV patients. In the multivariable Cox hazards model analysis, CVD during follow-up was significantly associated with both Birmingham vasculitis activity score (BVAS) (HR 1.159) and MetS at diagnosis (HR 9.036) in nonobese AAV patients.

Conclusions: The prevalence of MetS at diagnosis in all or nonobese AAV patients was significantly higher than those in all or nonobese controls. Furthermore, both BVAS and MetS at diagnosis increased the risk of CVD in nonobese AAV patients.
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http://dx.doi.org/10.1007/s00296-021-04908-1DOI Listing
June 2021

The Efficacy of Mycophenolate Mofetil in Remission Maintenance Therapy for Microscopic Polyangiitis and Granulomatosis with Polyangiitis.

Yonsei Med J 2021 Jun;62(6):494-502

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

Purpose: The present study compared the efficacy of mycophenolate mofetil (MMF) with that of azathioprine (AZA) in Korean patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA).

Materials And Methods: The medical records of 69 patients with MPA and GPA who received cyclophosphamide and subsequently received AZA or MMF for remission maintenance therapy were reviewed. All-cause mortality, relapse, end-stage renal disease (ESRD), cerebrovascular accident, and cardiovascular disease were evaluated as poor outcomes. Having a lower Birmingham Vasculitis Activity Score (BVAS) was defined as the lowest tertile of BVAS (BVAS ≤11 in this study).

Results: In comparative analysis of the occurrence of poor outcomes among patients taking AZA only, MMF only, and MMF after AZA, patients taking MMF only exhibited a significantly lower cumulative ESRD-free survival rate than patients taking AZA only (=0.028). In terms of ESRD occurrence between the groups based on BVAS at diagnosis, among patients with MPA and GPA with higher BVAS at diagnosis, patients taking MMF only exhibited a significantly lower cumulative ESRD-free survival rate than those taking AZA only (=0.047). Among patients with MPA and GPA with the lowest tertile of BVAS at diagnosis, cumulative ESRD-free survival rates did not differ.

Conclusion: With regard to ESRD occurrence, the efficacy of MMF in remission maintenance therapy was less effective than AZA in patients with MPA and GPA. However, among patients with lower BVAS, there was no difference in the occurrence of poor outcomes between patients taking MMF and those taking AZA.
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http://dx.doi.org/10.3349/ymj.2021.62.6.494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149928PMC
June 2021

Association between follistatin-related protein 1 and the functional status of patients with anti-neutrophil cytoplasmic antibody-associated vasculitis.

Chin Med J (Engl) 2021 Apr 14;134(10):1168-1174. Epub 2021 Apr 14.

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

Background: Follistatin-like 1 (FSTL1) plays both pro-inflammatory and anti-inflammatory roles in the inflammatory processes. We investigated whether serum FSTL1 could predict the current anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV)-specific indices.

Methods: We randomly selected 74 patients with AAV from a prospective and observational cohort of Korean patients with AAV. Clinical and laboratory data and AAV-specific indices were recorded. FSTL1 concentration was determined using the stored sera. The lowest tertile of the short-form 36-item health survey (SF-36) was defined as the current low SF-36. The cutoffs of serum FSTL1 for the current low SF-36 physical component summary (PCS) and SF-36 mental component summary (MCS) were extrapolated by the receiver operator characteristic curve.

Results: The median age was 62.5 years (55.4% were women). Serum FSTL1 was significantly correlated with SF-36 PCS (r =  - 0.374), SF-36 MCS (r = -0.377), and C-reactive protein (CRP) (r = 0.307), but not with Birmingham vasculitis activity score (BVAS). In the multivariable linear regression analyses, BVAS, CRP, and serum FSTL1 were independently associated with the current SF-36 PCS (β = -0.255, β = -0.430, and β = -0.266, respectively) and the current SF-36 MCS (β = -0.234, β =-0.229, and β = -0.296, respectively). Patients with serum FSTL1 ≥779.8 pg/mL and those with serum FSTL1 ≥841.6 pg/mL exhibited a significantly higher risk of having the current low SF-36 PCS and SF-36 MCS than those without (relative risk 7.583 and 6.200, respectively).

Conclusion: Serum FSTL1 could predict the current functional status in AAV patients.
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http://dx.doi.org/10.1097/CM9.0000000000001454DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143737PMC
April 2021

Serum galectin-9 could be a potential biomarker in assessing the disease activity of antineutrophil cytoplasmic antibody-associated vasculitis.

Clin Exp Rheumatol 2021 May 10. Epub 2021 May 10.

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

Objectives: Serum galectin levels have been reported to be associated with the activity in autoimmune diseases. This study investigated whether serum levels of galectin (Gal)-1, Gal-3, and Gal-9 could be used as biomarkers in assessing the disease activity of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).

Methods: Eighty AAV patients were selected for inclusion in our AAV cohort. AAV-specific indices and clinical and laboratory data were assessed on the same day when blood samples were obtained from the patient and serum levels of Gal-1, Gal-3, and Gal-9 were measured by ELISA from obtained sera. High disease activity was defined as Birmingham vasculitis activity score (BVAS) ≥ 12. The optimal cut-off value of galectins was extrapolated by receiver operator characteristic analysis and linear and logistic regression analyses were performed to evaluate the association between Gal-3, Gal-9, and BVAS.

Results: The median values of BVAS, Gal-1, Gal-3, and Gal-9 were 8.0, 38.1 ng/mL, 12.4 ng/mL, and 1017.7 ng/mL, respectively. Serum Gal-3 and Gal-9 levels were correlated with BVAS (r=0.375 and r=0.462), while only serum Gal-9 levels were independently associated with BVAS (β=0.250) in linear regression analyses. Serum Gal-9 ≥10.28 ng/mL was also associated with high activity of AAV (odds ratio 5.303) in multivariable logistic regression analysis. In addition, serum Gal-1, Gal-3, and Gal-9 levels were found to differ according to ANCA positivity status and the presence of renal manifestations.

Conclusions: These results suggest the potential possibility of serum Gal-9 levels in assessing AAV disease activity.
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May 2021

Male Sex Is a Significant Predictor of All-cause Mortality in Patients with Antineutrophil Cytoplasmic Antibody-associated Vasculitis.

J Korean Med Sci 2021 May 10;36(18):e120. Epub 2021 May 10.

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

Background: We investigated and compared the initial clinical features at diagnosis and the poor outcomes during follow-up in Korean patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) based on sex.

Methods: The medical records of 223 immunosuppressive drug-naïve patients with AAV were reviewed. Age, body mass index (BMI), smoking history, AAV subtypes, ANCA positivity, clinical manifestations, Birmingham vasculitis activity score (BVAS), five-factor score (FFS), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) at diagnosis were collected. All-cause mortality, end-stage renal disease (ESRD), cerebrovascular accident (CVA) and cardiovascular disease (CVD) were assessed as the poor outcomes of AAV during follow-up.

Results: The median age was 59.0 years and 74 of 223 AAV patients (33.2%) were men. Among variables at diagnosis, male patients exhibited higher BMI than female. However, there were no differences in other demographic data, AAV subtypes, ANCA positivity, BVAS, FFS, ESR and CRP between the two groups. Male patients received cyclophosphamide more frequently, but there were no significant differences in the frequencies of the poor outcomes of AAV between the two groups. Male patients exhibited a significantly lower cumulative patients' survival rate than female patients during the follow-up period based on all-cause mortality ( = 0.037). In the multivariable analysis, both male sex (hazard ratio [HR], 2.378) and FFS (HR, 1.693) at diagnosis were significantly and independently associated with all-cause mortality during follow-up.

Conclusion: Male sex is a significant and independent predictor of all-cause mortality in AAV patients.
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http://dx.doi.org/10.3346/jkms.2021.36.e120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111045PMC
May 2021

Association Between Serum Alarmin Levels and Disease-specific Indices in Patients With Anti-neutrophil Cytoplasmic Antibody-associated Vasculitis.

In Vivo 2021 May-Jun;35(3):1761-1768

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

Background/aim: We evaluated the relationship between serum alarmin levels and disease-specific indices in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).

Patients And Methods: Sera and data from 79 patients were utilized. For AAV-specific indices, Birmingham vasculitis activity score (BVAS), five-factor score (FFS), and vasculitis damage index (VDI) were collected and serum levels of four alarmins (hepatoma-derived growth factor, high mobility group box protein 1, S100A9, and S100A12) were measured using enzyme-linked immunosorbent assay. Associations between alarmin levels, AAV-specific indices, and inflammatory laboratory markers were assessed.

Results: S100A9 levels were significantly correlated with C-reactive protein levels (r=0.316, p=0.005) and S100A12 levels correlated with VDI (r=0.232, p=0.040), which was consistent in a subgroup of patients with myeloperoxidase (perinuclear)-ANCA positivity. No other associations were found between alarmin levels and BVAS, FFS, and VDI.

Conclusion: The serum S100A12 level was associated with organ damage in AAV, especially in myeloperoxidase (perinuclear)-ANCA-positive patients.
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http://dx.doi.org/10.21873/invivo.12435DOI Listing
January 2021

Unclassifiable repeated antineutrophil cytoplasmic antibody (ANCA) positivity in diseases other than ANCA-associated vasculitis.

Z Rheumatol 2021 Apr 27. Epub 2021 Apr 27.

Division of Rheumatology, Department of Internal Medicine, Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, 03722, Seoul, Korea (Republic of).

Background And Objective: Antineutrophil cytoplasmic antibody (ANCA) is a specific autoantibody for ANCA-associated vasculitis (AAV). However, ANCA can be detected in various diseases other than AAV. Hence, in this study, we investigated and provided the name of diseases with repeated ANCA positivity and the frequency of each disease other than AAV.

Methods: We retrospectively screened the results of the tests of ANCA in 26,499 patients using the Clinical Data Repository System and included in this study only 173 patients with repeated ANCA positivity more than twice. 'Unclassifiable ANCA' was defined when ANCA was detected in patients with diseases other than AAV. 'Unclassifiable repeated ANCA' was also defined when unclassifiable ANCA was successively detected more than twice.

Results: Among rheumatic and autoimmune diseases, the most common disease with unclassifiable repeated ANCA was vasculitis undetermined (21.0%). In terms of cardiovascular and cerebrovascular diseases, the most common disease with unclassifiable repeated ANCA was atherosclerotic heart disease (12.1%). In terms of disorders in liver, kidneys and lungs, the most common disease with unclassifiable repeated ANCA was chronic kidney disease (51 cases, 29.5%). In addition, among infections with confirmed infectious pathogens, the most common pathogen with unclassifiable repeated ANCA was varicella-zoster virus (6.9%) followed by Candida (4.6%).

Conclusion: Overall, regardless of category, the common diseases with unclassifiable repeated ANCA were chronic kidney disease followed by interstitial lung disease and vasculitis undetermined. Thus, we carefully suggest that physicians should pay more attention to the development of AAV or vasculitis other than AAV and, furthermore, kidneys and lungs should be monitored regularly and closely in patients with unclassifiable repeated ANCA.
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http://dx.doi.org/10.1007/s00393-021-00998-1DOI Listing
April 2021

An Increased Lateral Femoral Condyle Ratio Is an Important Risk Factor for a Medial Meniscus Ramp Lesion Including Red-Red Zone Tear.

Arthroscopy 2021 Apr 20. Epub 2021 Apr 20.

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

Purpose: This study aimed to determine radiological findings associated with ramp lesions in knees with anterior cruciate ligament (ACL) injury.

Methods: This study included the primary ACL reconstructions from June 2011 to March 2019. The exclusion criteria were combined fractures and multiligament injuries. Patients were categorized based on arthroscopy-confirmed presence of ramp lesions, which was defined as a longitudinal tear around the meniscocapsular junction or red-red zone tear of medial meniscus posterior horn. Binary logistic regression analysis was performed to find the risk factors such as age, sex, body mass index, medial tibial slope, mechanical axis angle, presence of Segond fracture, and lateral femoral condyle (LFC) ratio. Additionally, receiver operating characteristic (ROC) curves and area under the ROC curve (AUC) were evaluated.

Results: Ramp lesions were identified in 89 (27.7%) patients among the total 321 included primary ACL reconstructions. The risk of ramp lesion was associated with increased LFC ratio (odds ratio [OR]: 62.929; 95% confidence interval [CI]: 8.473-467.351; P < .001), varus alignment >3° (OR: 5.858; 95% CI: 3.272-10.486; P < .001), and steeper medial tibial slope (OR: 1.183; 95% CI: 1.05-1.333; P = .006). The cutoff values of the LFC ratio and medial tibial slope for ramp lesions were >71% (AUC: 0.696; sensitivity: 43.82%; specificity: 91.38%; P < .001) and >12.1° (AUC: 0.643; sensitivity: 85.39%; specificity: 38.79%; P < .001), respectively.

Conclusion: Deep posterior LFC, varus alignment, and steep medial tibial slope were associated factors for ramp lesions in knees with ACL injury. In patients with ACL injury who show the above-mentioned radiographic findings, careful assessment and suspicion for ramp lesions should be considered.

Study Design: Level III, retrospective cross-sectional study.
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http://dx.doi.org/10.1016/j.arthro.2021.03.078DOI Listing
April 2021

Aortic valve surgery in patients with Takayasu's arteritis: a nationwide analysis of 1,197 patients during a 9-year period.

Clin Exp Rheumatol 2021 Apr 7. Epub 2021 Apr 7.

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

Objectives: Takayasu's arteritis (TAK) is associated with an elevated risk of valvular heart disease, especially in the aortic valve. This study aimed to evaluate the rate and risk factors of aortic valve surgery (AVS) in patients with TAK.

Methods: The clinical data of 1,197 patients were identified in the Korean National Health Insurance Claims database between 2010 and 2018. Case ascertainment was done by using the ICD-10 code of TAK and inclusion in the Rare Intractable Diseases registry. The incidence rate/1,000 person-years was calculated to compare the age- and sex- adjusted incidence rate ratio (IRR) of AVS according to the time period between TAK diagnosis and AVS: <1 year, 1-2 years, 2-3 years, and 3 years. Evaluation of factors associated with AVS was performed using a time-dependent Cox regression analysis.

Results: Forty-five patients (3.8%) underwent AVS during the follow-up. The mean follow-up duration of patients with AVS was 1.2 years, and two-thirds of the patients (66.7%) underwent AVS within 1 year. The adjusted IRR was significantly higher among patients who underwent AVS <1 year after the diagnosis of TA than among those who underwent AVS ≥3 years after diagnosis (adjusted IRR: 10.31; 95% confidence interval [CI]: 4.29-24.81). A history of hypertension before the diagnosis of TAK was an independent risk factor for AVS (adjusted hazard ratio: 2.18; 95% CI: 1.12-4.24).

Conclusions: Approximately 4% of patients with TAK undergo AVS, usually within the first year of TAK diagnosis. Previous history of hypertension is a risk factor for AVS.
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April 2021

Risk of Stroke in Systemic Necrotizing Vasculitis: A Nationwide Study Using the National Claims Database.

Front Immunol 2021 31;12:629902. Epub 2021 Mar 31.

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

Objective: Evidences indicate that the risk of stroke is increased in autoimmune rheumatic diseases. This study aimed to investigate the incidence of stroke in patients with systemic necrotizing vasculitis (SNV) using the national health database.

Methods: Data were obtained from the Korean National Claims database between 2010 and 2018 to identify incident SNV [anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) and polyarteritis nodosa (PAN)] cases. The standardized incidence ratio (SIR) and incidence rate ratio (IRR) were calculated to estimate the risk of stroke in patients with SNV compared to the general population and among disease subgroups. Time-dependent Cox's regression analysis was performed to identify risk factors for stroke.

Results: Among 2644 incident SNV cases, 159 patients (6.0%) were affected by stroke. The overall risk of stroke was significantly higher in patients with SNV compared to the general population (SIR 8.42). Stroke event rates were the highest within the first year of SNV diagnosis (67.3%). Among disease subgroups, patients with microscopic polyangiitis (MPA) exhibited higher IRR compared to PAN (adjusted IRR 1.98). In Cox's hazard analysis, older age and MPA were associated with higher risk of stroke [hazard ratio (HR) 1.05 and 1.88], whereas the administration of cyclophosphamide, azathioprine/mizoribine, methotrexate, and statins were protective in stroke (HR 0.26, 0.34, 0.49, and 0.50, respectively).

Conclusion: A considerable number of SNV patients experienced stroke, especially in the early phase of disease. Older age and MPA diagnosis were associated with elevated risk of stroke, while the administration of immunosuppressive agents and statins was beneficial in preventing stroke.
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http://dx.doi.org/10.3389/fimmu.2021.629902DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046646PMC
March 2021

The novel fibrosis index at diagnosis may predict all-cause mortality in patients with antineutrophil cytoplasmic antibody-associated vasculitis without substantial liver diseases.

Clinics (Sao Paulo) 2021 9;76:e2501. Epub 2021 Apr 9.

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

Objectives: Antineutrophil cyto plasmic antibody-associated vasculitis (AAV) is a fatal disease. Currently, predictors of mortality due to AAV are based on the distribution of organ involvement. The novel fibrosis index (NFI) is an index composed of laboratory results that reflect the degree of liver fibrosis. This study aimed to evaluate whether NFI can predict poor outcomes in patients with AAV without substantial liver disease.

Methods: A total of 210 patients with immunosuppressive drug-naïve AAV were retrospectively reviewed. NFI was calculated as follows: NFI=(serum bilirubin × (alkaline phosphatase)2)/(platelet count×(serum albumin)2). NFI cut-off was set at 1.24 (the highest quartile). Poor outcomes were defined as all-cause mortality, relapse, and end-stage renal disease (ESRD).

Results: During the median 34.5 months of follow-up, 21 patients (10%) died, 72 patients (34.3%) relapsed, and 38 patients (18.1%) had ESRD due to AAV progression. The median calculated NFI was 0.61, and it was higher in AAV patients with all-cause mortality than in those without mortality, but the difference was not statistically significant (1.26 vs. 0.59). AAV patients with NFI at diagnosis ≥1.24 exhibited a significantly lower cumulative patient survival rate than those with NFI at diagnosis <1.24 (p=0.002). Multivariate Cox hazard model analysis showed that NFI at diagnosis ≥1.24 was an independent predictor of all-cause mortality in AAV (hazard ratios [HR] 2.850, 95% confidence interval [CI] 1.026, 7.910).

Conclusions: NFI ≥1.24, which may be an independent predictive marker for all-cause mortality in AAV patients without substantial liver disease.
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http://dx.doi.org/10.6061/clinics/2021/e2501DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009064PMC
April 2021

Is it worth to perform initial non-operative treatment for patients with acute ACL injury?: a prospective cohort prognostic study.

Knee Surg Relat Res 2021 Apr 6;33(1):11. Epub 2021 Apr 6.

Department of Orthopedic Surgery, Jeju National University Hospital, Jeju National University School of Medicine, Aran 13gil 15, Jeju-si, Jeju Self-Governing Province, 63241, South Korea.

Purpose: To evaluate the result of implementing an initial non-operative treatment program for an acute ACL injury and to find if the timing of initiating the non-operative treatment is significant.

Methods: This study included a prospective cohort of 85 consecutive patients with acute ACL injury who were treated according to the above strategy for the initial 3 months with 1-year follow-up. Clinical evaluations were made by Lysholm score, Tegner activity score, Lachman test (LT), pivot-shit test (PST), and the side to side difference (SSD) by KT-2000 arthrometer. The results were analyzed according to the timing of initiating the non-operative treatment.

Results: Initially, 84% of the patients showed LT and PST ≤ grade 1, and 16% with ≥grade 2. At 1-year follow-up, 77 patients (91%) with LT and PST ≤ grade 1 did not receive reconstruction as copers and 8 patients with LT or PST ≥ grade 2 required reconstruction (six patients received the operation and two refused). The patients with LT and PST ≤ grade 1 showed average Lysholm score 91.2, average SSD 2.5 mm, and mean Tegner score decreased from 6.9 (pre-injury) to 6.2. Patients who started the non-operative treatment within 2 weeks after injury revealed superior rates of grade 0 or 1 instability than those who commenced the treatment later than 2 weeks after injury (P = 0.043).

Conclusions: Implementing a non-operative treatment with brace in acute phase of ACL injury appears to be an effective and viable option to achieve a reasonable clinical outcome. We recommend earlier initiation of the non-operative treatment to obtain a better result in patients with acute ACL injury.
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http://dx.doi.org/10.1186/s43019-021-00094-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025569PMC
April 2021

Serological Biomarkers and Indices for the Current Activity and Prognosis of ANCA-Associated Vasculitis: Experience in a Single Centre in Korea.

Yonsei Med J 2021 Apr;62(4):279-287

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

Small vessel vasculitis is composed of two types of vasculitis based on immune-complex deposits, immune-complex vasculitis and antineutrophil cytoplasmic antibody-associated vasculitis (AAV) according to the 2012 Chapel Hill Consensus Conferences Nomenclature of Vasculitis. In general, the current disease-states are assessed in three ways in real clinical practice such as activity, damage and functional status. Birmingham vasculitis activity score (BVAS, version 3) and five-factor score were calculated for assessing the cross-sectional activity and for predicting the prognosis of AAV, respectively. Since BVAS includes a wide spectrum of nine systemic items with differently weighted scores based on new-onset/worsening or persistent each symptom, it has been considered as the most reliable tool to assess AAV activity to date. However, since BVAS represents both cross-sectional and chronic clinical features, it has a limitation in flexibly reflecting the cross-sectional activity or severity of AAV. In addition, the heterogeneous items of BVAS are difficult to reflect the close correlation between BVAS and AAV pathogenesis. It is practically difficult to discover new biomarkers or indices that exceed the reliability of AAV-specific indices or acute-phase reactants established by long clinical experience. However, efforts to discover and develop new biomarkers or indices are expected to complement the clinical unmet need of existing AAV-specific indices and acute-phase reactants. In this review, we reviewed the serological biomarkers and indices that have been reported to date and introduced studies that investigated serological biomarkers and indices in Korean patients with AAV.
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http://dx.doi.org/10.3349/ymj.2021.62.4.279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007433PMC
April 2021

Injectable Fibrin/Polyethylene Oxide Semi-IPN Hydrogel for a Segmental Meniscal Defect Regeneration.

Am J Sports Med 2021 05 25;49(6):1538-1550. Epub 2021 Mar 25.

Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea.

Background: Meniscal deficiency from meniscectomy is a common situation in clinical practices. Regeneration of the deficient meniscal portion, however, is still not feasible.

Purpose: To develop an injectable hydrogel system consisting of fibrin (Fb) and polyethylene oxide (PEO) and to estimate its clinical potential for treating a segmental defect of the meniscus in a rabbit meniscal defect model.

Study Design: Controlled laboratory study.

Methods: The Fb/PEO hydrogel was fabricated by extruding 100 mg·mL of fibrinogen solution and 2,500 U·mL of thrombin solution containing 100 mg·mL of PEO through a dual-syringe system. The hydrogels were characterized by rheological analysis and biodegradation tests. The meniscal defects of New Zealand White male rabbits were generated by removing 60% of the medial meniscus from the anterior side. The removed portion included the central portion. The Fb/PEO hydrogel was injected into the meniscal defect of the experimental knee through the joint space between the femoral condyle and tibial plateau at the anterior knee without a skin incision. The entire medial menisci from both knees of each rabbit were collected and photographed before placement in formalin for histological processing. Hematoxylin and eosin, safranin O, and immunohistochemical staining for type II collagen was performed. The biomechanical property of the regenerated meniscus was evaluated using a universal tensile machine.

Results: The Fb/PEO hydrogel was fabricated by an in situ gelation process, and the hydrogel displayed a semi-interpenetrating polymer network structure. We demonstrated that the mechanical properties of Fb-based hydrogels increased in a PEO-dependent manner. Furthermore, the addition of PEO delayed the biodegradation of the hydrogel. Our in vivo data demonstrated that, as compared with Fb hydrogel, Fb/PEO hydrogel injection into the meniscectomy model showed improved tissue regeneration. The regenerated meniscal tissue by Fb/PEO hydrogel showed enhanced tissue quality, which was supported by the histological and biomechanical properties.

Conclusion: The Fb/PEO hydrogel had an effective tissue-regenerative ability through injection into the in vivo rabbit meniscal defect model.

Clinical Relevance: This injectable hydrogel system can promote meniscal repair and be readily utilized in clinical application.
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http://dx.doi.org/10.1177/0363546521998021DOI Listing
May 2021

Correlation between serum cysteine-rich protein 61 and disease activity of antineutrophil cytoplasmic antibody-associated vasculitis.

Clin Rheumatol 2021 Mar 23. Epub 2021 Mar 23.

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

Objectives: Cysteine-rich protein 61 (CYR61) stimulates protein kinase B (Akt)-mediated nuclear factor-kappa B (NF-κB) signalling leading to an increase in pro-inflammatory cytokines, which play important roles in the pathogenesis of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Hence, we investigated whether serum CYR61 was correlated with disease activity of AAV in a single-centre prospective cohort.

Methods: Seventy-two patients with AAV were randomly selected and included. Serum CYR61, interleukin (IL)-6 and IL-8 levels were quantified with the patients' stored sera, and clinical and laboratory data at the time of blood sampling were collected. Spearman's correlation and linear regression analysis was conducted to analyse the correlation between continuous variables. The optimal cut-off of serum CYR61 for predicting high disease activity was identified using the receiver operator characteristic curve. Birmingham vasculitis activity score (BVAS) was used as a measure to assess disease activity, and high disease activity was defined as BVAS ≥ 12.

Results: Serum CYR61 significantly correlated with BVAS (r = 0.249), erythrocyte sedimentation rate (r = 0.283), C-reactive protein (r = 0.298) and serum IL-6 (r = 0.319). However, a linear association was not found between CYR61 and BVAS (β = 0.102, P = 0.304). The relative risk (RR) for high disease activity in AAV patients with serum CYR61 ≥ 236.2 pg/mL was higher than those with serum CYR61 < 236.2 pg/mL (RR 3.316, P = 0.018).

Conclusion: Even though serum CYR61 was not directly proportional to the increase of BVAS, it could be predictive of high disease activity in AAV. Key Points • Serum CYR61 was significantly correlated with BVAS along with ESR, CRP and serum IL-6. • The cut-off of serum CYR61 for high disease activity of AAV was obtained as 236.2 pg/mL. • AAV patients with serum CYR61 ≥ 236.2 pg/mL had increased risk of having higher disease activity than those with serum CYR61 < 236.2 pg/mL (RR 3.316, P = 0.018).
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http://dx.doi.org/10.1007/s10067-021-05701-yDOI Listing
March 2021

Serum chitinase-3-like 1 protein is a useful biomarker to assess disease activity in ANCA-associated vasculitis: an observational study.

Arthritis Res Ther 2021 03 8;23(1):77. Epub 2021 Mar 8.

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

Background: To investigate whether serum chitinase-3-like 1 protein (YKL-40) is associated with disease activity in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).

Methods: ELISA was performed in serum samples from AAV patients who were enrolled in our prospective observational cohort to estimate levels of YKL-40. Birmingham vasculitis activity score (BVAS) (version 3), five factor score (FFS), and short form-36 (SF-36), as well as clinical and laboratory data were collected. Kidney expression of YKL-40 was assessed by immunohistochemical staining using renal biopsy tissues from ANCA-associated glomerulonephritis patients (AAGN). Severe AAV and FFS were defined as BVAS ≥ 12 and FFS ≥ 2, and the correlations between laboratory variables, BVAS, FFS, and SF-36 score were assessed using linear regression analysis. The optimal cut-off of serum YKL-40 for severe AAV and high FFS was calculated using the receiver operator characteristic curve analysis.

Results: Of the included 60 patients, 32 (53.3%), 17 (28.3%), and 11 (18.3%) were classified as microscopic polyangiitis, granulomatosis with polyangiitis, and eosinophilic granulomatosis with polyangiitis. The median BVAS and FFS were 7.0 and 1.0, whereas the mean SF-36 physical and mental component scores were 50.5 and 58.3. Serum YKL-40 level was higher in patients with severe AAV and high FFS compared to those without (p = 0.007 and p < 0.001); multivariable linear regression analysis revealed that serum YKL-40 was independently associated with BVAS, FFS, and SF-36 scores. On kidney tissues obtained from AAGN patients, strong cytoplasmic staining of YKL-40 was found in cells present in inflammatory lesions. In addition, AAV patients had higher levels of serum YKL-40 compared to those with systemic lupus erythematosus, rheumatoid arthritis, osteoarthritis, and healthy control. The proportion of patients having severe AAV and high FFS was significantly higher in those with serum YKL-40 > 221.3 ng/mL and > 227.1 ng/mL than those without (relative risk 2.852 and 7.000). In 12 patients with serial YKL-40 testing, 11 patients (91.7%) exhibited a reduction in serum YKL-40 levels following a decrease in disease activity (p < 0.001).

Conclusion: Our findings suggest that serum YKL-40 may be a clinically useful biomarker to assess AAV disease activity.

Trial Registration: Retrospectively registered.
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http://dx.doi.org/10.1186/s13075-021-02467-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938492PMC
March 2021

Fucoxanthin Suppresses Osteoclastogenesis via Modulation of MAP Kinase and Nrf2 Signaling.

Mar Drugs 2021 Feb 27;19(3). Epub 2021 Feb 27.

Division of Rheumatology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam 13620, Korea.

Fucoxanthin (FX), a natural carotenoid present in edible brown seaweed, is known for its therapeutic potential in various diseases, including bone disease. However, its underlying regulatory mechanisms in osteoclastogenesis remain unclear. In this study, we investigated the effect of FX on osteoclast differentiation and its regulatory signaling pathway. In vitro studies were performed using osteoclast-like RAW264.7 cells stimulated with the soluble receptor activator of nuclear factor-κB ligand or tumor necrosis factor-alpha/interleukin-6. FX treatment significantly inhibited osteoclast differentiation and bone resorption ability, and downregulated the expression of osteoclast-specific markers such as nuclear factor of activated T cells 1, dendritic cell-specific seven transmembrane protein, and matrix metallopeptidase 9. Intracellular signaling pathway analysis revealed that FX specifically decreased the activation of the extracellular signal-regulated kinase and p38 kinase, and increased the nuclear translocation of phosphonuclear factor erythroid 2-related factor 2 (Nrf2). Our results suggest that FX regulates the expression of mitogen-activated protein kinases and Nrf2. Therefore, FX is a potential therapeutic agent for osteoclast-related skeletal disorders including osteoporosis and rheumatoid arthritis.
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http://dx.doi.org/10.3390/md19030132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997314PMC
February 2021

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

Clin Exp Rheumatol 2021 Mar-Apr;39 Suppl 129(2):94-100. 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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May 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 Apr 16;35(4):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
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059749PMC
April 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