Publications by authors named "Sung Soo Ahn"

149 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

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

Magnetic Resonance Imaging Parameters for Noninvasive Prediction of Epidermal Growth Factor Receptor Amplification in Isocitrate Dehydrogenase-Wild-Type Lower-Grade Gliomas: A Multicenter Study.

Neurosurgery 2021 Apr 29. Epub 2021 Apr 29.

Department of Radiology and Research Institute of Radiological Science and Center for Clinical Imaging Data Science, Yonsei University College of Medicine, Seoul, South Korea.

Background: The epidermal growth factor receptor (EGFR) amplification status of isocitrate dehydrogenase-wild-type (IDHwt) lower-grade gliomas (LGGs; grade II/III) is one of the key markers for diagnosing molecular glioblastoma. However, the association between EGFR status and imaging parameters is unclear.

Objective: To identify noninvasive imaging parameters from diffusion-weighted and dynamic susceptibility contrast imaging for predicting the EGFR amplification status of IDHwt LGGs.

Methods: A total of 86 IDHwt LGG patients with known EGFR amplification status (62 nonamplified and 24 amplified) from 3 tertiary institutions were included. Qualitative and quantitative imaging features, including histogram parameters from apparent diffusion coefficient (ADC), normalized cerebral blood volume (nCBV), and normalized cerebral blood flow (nCBF), were assessed. Univariable and multivariable logistic regression models were constructed.

Results: On multivariable analysis, multifocal/multicentric distribution (odds ratio [OR] = 11.77, P = .006), mean ADC (OR = 0.01, P = .044), 5th percentile of ADC (OR = 0.01, P = .046), and 95th percentile of nCBF (OR = 1.24, P = .031) were independent predictors of EGFR amplification. The diagnostic performance of the model with qualitative imaging parameters increased significantly when quantitative imaging parameters were added, with areas under the curves of 0.81 and 0.93, respectively (P = .004).

Conclusion: The presence of multifocal/multicentric distribution patterns, lower mean ADC, lower 5th percentile of ADC, and higher 95th percentile of nCBF may be useful imaging biomarkers for EGFR amplification in IDHwt LGGs. Moreover, quantitative imaging biomarkers may add value to qualitative imaging parameters.
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http://dx.doi.org/10.1093/neuros/nyab136DOI Listing
April 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
June 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

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

Quality assessment of meningioma radiomics studies: Bridging the gap between exploratory research and clinical applications.

Eur J Radiol 2021 May 20;138:109673. Epub 2021 Mar 20.

Department of Radiology and Research Institute of Radiological Science and Center for Clinical Imaging Data Science, Yonsei University College of Medicine, Seoul, Republic of Korea.

Purpose: To evaluate the quality of radiomics studies on meningiomas, using a radiomics quality score (RQS), Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD), and the Image Biomarker Standardization Initiative (IBSI).

Methods: PubMed MEDLINE and Embase were searched to identify radiomics studies on meningiomas. Of 138 identified articles, 25 relevant original research articles were included. Studies were scored according to the RQS, TRIPOD guidelines, and items in IBSI.

Results: Only four studies (16 %) performed external validation. The mean RQS was 5.6 out of 36 (15.4 %), and the basic adherence rate was 26.8 %. The adherence rate was low for stating biological correlation (4%), conducting calibration statistics (12 %), multiple segmentation (16 %), and stating potential clinical utility (16 %). None of the studies conducted a test‒retest or phantom study, stated a comparison to a 'gold standard', conducted prospective studies or cost-effectivity analysis, or opened code and data to the public, resulting in low RQS. The overall adherence rate for TRIPOD was 54.1 %, with low scores for reporting the title (4%), abstract (0%), blind assessment of the outcome (8%), and explaining the sample size (0%). According to IBSI items, only 6 (24 %), 6 (24 %), and 3 (12 %) studies performed N4 bias-field correction, isovoxel resampling, and grey-level discretization, respectively. No study performed skull stripping.

Conclusion: The quality of radiomics studies for meningioma is insufficient. Acknowledgement of RQS, TRIPOD, and IBSI reporting guidelines may improve the quality of meningioma radiomics studies and enable their clinical application.
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http://dx.doi.org/10.1016/j.ejrad.2021.109673DOI 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

Dynamic contrast-enhanced MRI may be helpful to predict response and prognosis after bevacizumab treatment in patients with recurrent high-grade glioma: comparison with diffusion tensor and dynamic susceptibility contrast imaging.

Neuroradiology 2021 Mar 23. Epub 2021 Mar 23.

Department of Radiology and Research Institute of Radiological Science and Center for Clinical Imaging Data Science, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Korea.

Purpose: We aimed to evaluate the utility of diffusion tensor imaging (DTI), dynamic contrast-enhanced (DCE), and dynamic susceptibility contrast (DSC) imaging for stratifying bevacizumab treatment outcomes in patients with recurrent high-grade glioma.

Methods: Fifty-three patients with recurrent high-grade glioma who underwent baseline magnetic resonance imaging including DTI, DCE, and DSC before bevacizumab treatment were included. The mean apparent diffusion coefficient, fractional anisotropy, normalized cerebral blood volume, normalized cerebral blood flow, volume transfer constant, rate transfer coefficient (K), extravascular extracellular volume fraction, and plasma volume fraction were assessed. Predictors of response status, progression-free survival (PFS), and overall survival (OS) were determined using logistic regression and Cox proportional hazard modeling.

Results: Responders (n = 16) showed significantly longer PFS and OS (P < 0.001) compared with nonresponders (n = 37). Multivariable analysis revealed that lower mean K (odds ratio = 0.01, P = 0.008) was the only independent predictor of favorable response after adjustment for age, isocitrate dehydrogenase (IDH) mutation status, and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status. Multivariable Cox proportional hazard modeling showed that a higher mean K was the only variable associated with shorter PFS (hazard ratio [HR] = 7.90, P = 0.006) and OS (HR = 9.71, P = 0.020) after adjustment for age, IDH mutation status, and MGMT promoter methylation status.

Conclusion: Baseline mean K may be a useful biomarker for predicting response and stratifying patient outcomes following bevacizumab treatment in patients with recurrent high-grade glioma.
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http://dx.doi.org/10.1007/s00234-021-02693-zDOI Listing
March 2021

Robust performance of deep learning for automatic detection and segmentation of brain metastases using three-dimensional black-blood and three-dimensional gradient echo imaging.

Eur Radiol 2021 Mar 18. Epub 2021 Mar 18.

Department of Radiology and Research Institute of Radiological Science and Center for Clinical Imaging Data Science, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, South Korea.

Objectives: To evaluate whether a deep learning (DL) model using both three-dimensional (3D) black-blood (BB) imaging and 3D gradient echo (GRE) imaging may improve the detection and segmentation performance of brain metastases compared to that using only 3D GRE imaging.

Methods: A total of 188 patients with brain metastases (917 lesions) who underwent a brain metastasis MRI protocol including contrast-enhanced 3D BB and 3D GRE were included in the training set. DL models based on 3D U-net were constructed. The models were validated in the test set consisting of 45 patients with brain metastases (203 lesions) and 49 patients without brain metastases.

Results: The combined 3D BB and 3D GRE model yielded better performance than the 3D GRE model (sensitivities of 93.1% vs 76.8%, p < 0.001), and this effect was significantly stronger in subgroups with small metastases (p interaction < 0.001). For metastases < 3 mm, ≥ 3 mm and < 10 mm, and ≥ 10 mm, the sensitivities were 82.4%, 93.2%, and 100%, respectively. The combined 3D BB and 3D GRE model showed a false-positive per case of 0.59 in the test set. The combined 3D BB and 3D GRE model showed a Dice coefficient of 0.822, while 3D GRE model showed a lower Dice coefficient of 0.756.

Conclusions: The combined 3D BB and 3D GRE DL model may improve the detection and segmentation performance of brain metastases, especially in detecting small metastases.

Key Points: • The combined 3D BB and 3D GRE model yielded better performance for the detection of brain metastases than the 3D GRE model (p < 0.001), with sensitivities of 93.1% and 76.8%, respectively. • The combined 3D BB and 3D GRE model showed a false-positive rate per case of 0.59 in the test set. • The combined 3D BB and 3D GRE model showed a Dice coefficient of 0.822, while the 3D GRE model showed a lower Dice coefficient of 0.756.
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http://dx.doi.org/10.1007/s00330-021-07783-3DOI Listing
March 2021

Clinical and diffusion parameters may noninvasively predict TERT promoter mutation status in grade II meningiomas.

J Neuroradiol 2021 Mar 11. Epub 2021 Mar 11.

Department of Radiology and Research Institute of Radiological Science and Center for Clinical Imaging Data Science, Yonsei University College of Medicine, Seoul, South Korea.

Background And Purpose: Increasing evidence suggests that genomic and molecular markers need to be integrated in grading of meningioma. Telomerase reverse transcriptase promoter (TERTp) mutation is receiving attention due to its clinical relevance in the treatment of meningiomas. The predictive ability of conventional and diffusion MRI parameters for determining the TERTp mutation status in grade II meningiomas has yet been identified.

Material And Methods: In this study, 63 patients with surgically confirmed grade II meningiomas (56 TERTp wildtype, 7 TERTp mutant) were included. Conventional imaging features were qualitatively assessed. The maximum diameter, volume of the tumors and histogram parameters from the apparent diffusion coefficient (ADC) were assessed. Independent clinical and imaging risk factors for TERTp mutation were investigated using multivariable logistic regression. The discriminative value of the prediction models with and without imaging features was evaluated.

Results: In the univariable regression, older age (odds ratio [OR] = 1.13, P = 0.005), larger maximum diameter (OR = 1.09, P = 0.023), larger volume (OR = 1.04, P = 0.014), lower mean ADC (OR = 0.02, P = 0.025), and lower ADC 10th percentile (OR = 0.01, P = 0.014) were predictors of TERTp mutation. In multivariable regression, age (OR = 1.13, P = 0.009) and ADC 10th percentile (OR = 0.01, P = 0.038) were independent predictors of variables for predicting the TERTp mutation status. The performance of the prediction model increased upon inclusion of imaging parameters (area under the curves of 0.86 and 0.91, respectively, without and with imaging parameters).

Conclusion: Older age and lower ADC 10th percentile may be useful parameters to predict TERTp mutation in grade II meningiomas.
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http://dx.doi.org/10.1016/j.neurad.2021.02.007DOI Listing
March 2021

Radiomics with Ensemble Machine Learning Predicts Dopamine Agonist Response in Patients with Prolactinoma.

J Clin Endocrinol Metab 2021 Mar 13. Epub 2021 Mar 13.

Department of Radiology and Research Institute of Radiological Science and Center for Clinical Imaging Data Science, Yonsei University College of Medicine, Seoul, Korea.

Context: Early identification of the response of prolactinoma patients to dopamine agonists (DA) is crucial in treatment planning.

Objective: To develop a radiomics model using an ensemble machine learning classifier with conventional magnetic resonance images (MRIs) to predict the DA response in prolactinoma patients.

Design: Retrospective study.

Setting: Severance Hospital.

Patients: A total of 177 prolactinoma patients who underwent baseline MRI (109 DA responders and 68 DA non-responders) were allocated to the training (n = 141) and test (n = 36) sets. Radiomic features (n = 107) were extracted from coronal T2-weighed MRIs. After feature selection, single models (random forest, light gradient boosting machine, extra-trees, quadratic discrimination analysis, and linear discrimination analysis) with oversampling methods were trained to predict the DA response. A soft voting ensemble classifier was used to achieve the final performance. The performance of the classifier was validated in the test set.

Results: The ensemble classifier showed an area under the curve (AUC) of 0.81 (95 % confidence interval [CI], 0.74-0.87) in the training set. In the test set, the ensemble classifier showed an AUC, accuracy, sensitivity, and specificity of 0.81 (95 % CI, 0.67-0.96), 77.8 %, 78.6 %, and 77.3 %, respectively. The ensemble classifier achieved the highest performance among all the individual models in the test set.

Conclusions: Radiomic features may be useful biomarkers to predict the DA response in prolactinoma patients.
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http://dx.doi.org/10.1210/clinem/dgab159DOI 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

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

Differentiation of recurrent glioblastoma from radiation necrosis using diffusion radiomics with machine learning model development and external validation.

Sci Rep 2021 Feb 3;11(1):2913. Epub 2021 Feb 3.

Department of Radiology and Research Institute of Radiological Science and Center for Clinical Image Data Science, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, South Korea.

The purpose of this study was to establish a high-performing radiomics strategy with machine learning from conventional and diffusion MRI to differentiate recurrent glioblastoma (GBM) from radiation necrosis (RN) after concurrent chemoradiotherapy (CCRT) or radiotherapy. Eighty-six patients with GBM were enrolled in the training set after they underwent CCRT or radiotherapy and presented with new or enlarging contrast enhancement within the radiation field on follow-up MRI. A diagnosis was established either pathologically or clinicoradiologically (63 recurrent GBM and 23 RN). Another 41 patients (23 recurrent GBM and 18 RN) from a different institution were enrolled in the test set. Conventional MRI sequences (T2-weighted and postcontrast T1-weighted images) and ADC were analyzed to extract 263 radiomic features. After feature selection, various machine learning models with oversampling methods were trained with combinations of MRI sequences and subsequently validated in the test set. In the independent test set, the model using ADC sequence showed the best diagnostic performance, with an AUC, accuracy, sensitivity, specificity of 0.80, 78%, 66.7%, and 87%, respectively. In conclusion, the radiomics models models using other MRI sequences showed AUCs ranging from 0.65 to 0.66 in the test set. The diffusion radiomics may be helpful in differentiating recurrent GBM from RN..
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http://dx.doi.org/10.1038/s41598-021-82467-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7858615PMC
February 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

Predicting Amyloid Pathology in Mild Cognitive Impairment Using Radiomics Analysis of Magnetic Resonance Imaging.

J Alzheimers Dis 2021 ;79(2):483-491

Department of Radiology and Research Institute of Radiological Science and Center for Clinical Imaging Data Science, Yonsei University College of Medicine, Seoul, Korea.

Background: Noninvasive identification of amyloid-β (Aβ) is important for better clinical management of mild cognitive impairment (MCI) patients.

Objective: To investigate whether radiomics features in the hippocampus in MCI improve the prediction of cerebrospinal fluid (CSF) Aβ42 status when integrated with clinical profiles.

Methods: A total of 407 MCI subjects from the Alzheimer's Disease Neuroimaging Initiative were allocated to training (n = 324) and test (n = 83) sets. Radiomics features (n = 214) from the bilateral hippocampus were extracted from magnetic resonance imaging (MRI). A cut-off of <192 pg/mL was applied to define CSF Aβ42 status. After feature selection, random forest with subsampling methods were utilized to develop three models with which to predict CSF Aβ42: 1) a radiomics model; 2) a clinical model based on clinical profiles; and 3) a combined model based on radiomics and clinical profiles. The prediction performances thereof were validated in the test set. A prediction model using hippocampus volume was also developed and validated.

Results: The best-performing radiomics model showed an area under the curve (AUC) of 0.674 in the test set. The best-performing clinical model showed an AUC of 0.758 in the test set. The best-performing combined model showed an AUC of 0.823 in the test set. The hippocampal volume model showed a lower performance, with an AUC of 0.543 in the test set.

Conclusion: Radiomics models from MRI can help predict CSF Aβ42 status in MCI patients and potentially triage the patients for invasive and costly Aβ tests.
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http://dx.doi.org/10.3233/JAD-200734DOI Listing
January 2021

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

Int J Clin Pract 2021 Apr 20;75(4):e13929. Epub 2020 Dec 20.

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
April 2021

Deep-learned time-signal intensity pattern analysis using an autoencoder captures magnetic resonance perfusion heterogeneity for brain tumor differentiation.

Sci Rep 2020 12 8;10(1):21485. Epub 2020 Dec 8.

Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 43 Olympic-ro 88, Songpa-Gu, Seoul, 05505, Korea.

Current image processing methods for dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI) do not capture complex dynamic information of time-signal intensity curves. We investigated whether an autoencoder-based pattern analysis of DSC MRI captured representative temporal features that improves tissue characterization and tumor diagnosis in a multicenter setting. The autoencoder was applied to the time-signal intensity curves to obtain representative temporal patterns, which were subsequently learned by a convolutional neural network. This network was trained with 216 preoperative DSC MRI acquisitions and validated using external data (n = 43) collected with different DSC acquisition protocols. The autoencoder applied to time-signal intensity curves and clustering obtained nine representative clusters of temporal patterns, which accurately identified tumor and non-tumoral tissues. The dominant clusters of temporal patterns distinguished primary central nervous system lymphoma (PCNSL) from glioblastoma (AUC 0.89) and metastasis from glioblastoma (AUC 0.95). The autoencoder captured DSC time-signal intensity patterns that improved identification of tumoral tissues and differentiation of tumor type and was generalizable across centers.
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http://dx.doi.org/10.1038/s41598-020-78485-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723041PMC
December 2020

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

Clin Exp Rheumatol 2021 Mar-Apr;39 Suppl 129(2):88-93. 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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May 2021

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 01 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

Radiomics features of hippocampal regions in magnetic resonance imaging can differentiate medial temporal lobe epilepsy patients from healthy controls.

Sci Rep 2020 11 11;10(1):19567. Epub 2020 Nov 11.

Department of Neurology, Epilepsy and Sleep Center, Ewha Womans University School of Medicine and Ewha Medical Research Institute, 1071, Anyangcheon-ro, Yangcheon-gu, Seoul, 07985, Korea.

To investigative whether radiomics features in bilateral hippocampi from MRI can identify temporal lobe epilepsy (TLE). A total of 131 subjects with MRI (66 TLE patients [35 right and 31 left TLE] and 65 healthy controls [HC]) were allocated to training (n = 90) and test (n = 41) sets. Radiomics features (n = 186) from the bilateral hippocampi were extracted from T1-weighted images. After feature selection, machine learning models were trained. The performance of the classifier was validated in the test set to differentiate TLE from HC and ipsilateral TLE from HC. Identical processes were performed to differentiate right TLE from HC (training set, n = 69; test set; n = 31) and left TLE from HC (training set, n = 66; test set, n = 30). The best-performing model for identifying TLE showed an AUC, accuracy, sensitivity, and specificity of 0.848, 84.8%, 76.2%, and 75.0% in the test set, respectively. The best-performing radiomics models for identifying right TLE and left TLE subgroups showed AUCs of 0.845 and 0.840 in the test set, respectively. In addition, multiple radiomics features significantly correlated with neuropsychological test scores (false discovery rate-corrected p-values < 0.05). The radiomics model from hippocampus can be a potential biomarker for identifying TLE.
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http://dx.doi.org/10.1038/s41598-020-76283-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7658973PMC
November 2020

Quality Reporting of Radiomics Analysis in Mild Cognitive Impairment and Alzheimer's Disease: A Roadmap for Moving Forward.

Korean J Radiol 2020 12 30;21(12):1345-1354. Epub 2020 Oct 30.

Department of Radiology, Research Institute of Radiological Science and Center for Clinical Imaging Data Science, Yonsei University College of Medicine, Seoul, Korea.

Objective: To evaluate radiomics analysis in studies on mild cognitive impairment (MCI) and Alzheimer's disease (AD) using a radiomics quality score (RQS) system to establish a roadmap for further improvement in clinical use.

Materials And Methods: PubMed MEDLINE and EMBASE were searched using the terms 'cognitive impairment' or 'Alzheimer' or 'dementia' and 'radiomic' or 'texture' or 'radiogenomic' for articles published until March 2020. From 258 articles, 26 relevant original research articles were selected. Two neuroradiologists assessed the quality of the methodology according to the RQS. Adherence rates for the following six key domains were evaluated: image protocol and reproducibility, feature reduction and validation, biologic/clinical utility, performance index, high level of evidence, and open science.

Results: The hippocampus was the most frequently analyzed (46.2%) anatomical structure. Of the 26 studies, 16 (61.5%) used an open source database (14 from Alzheimer's Disease Neuroimaging Initiative and 2 from Open Access Series of Imaging Studies). The mean RQS was 3.6 out of 36 (9.9%), and the basic adherence rate was 27.6%. Only one study (3.8%) performed external validation. The adherence rate was relatively high for reporting the imaging protocol (96.2%), multiple segmentation (76.9%), discrimination statistics (69.2%), and open science and data (65.4%) but low for conducting test-retest analysis (7.7%) and biologic correlation (3.8%). None of the studies stated potential clinical utility, conducted a phantom study, performed cut-off analysis or calibration statistics, was a prospective study, or conducted cost-effectiveness analysis, resulting in a low level of evidence.

Conclusion: The quality of radiomics reporting in MCI and AD studies is suboptimal. Validation is necessary using external dataset, and improvements need to be made to feature reproducibility, feature selection, clinical utility, model performance index, and pursuits of a higher level of evidence.
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http://dx.doi.org/10.3348/kjr.2020.0715DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7689149PMC
December 2020