Purpose: This study aimed to investigate whether the serum extracellular newly identified receptor for advanced glycation end products binding protein (EN-RAGE) and the soluble form of RAGE (sRAGE) measured at diagnosis are associated with all-cause mortality in patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). Materials and Methods: Serum EN-RAGE and sRAGE were measured in 75 immunosuppressive drug-naïve MPA and GPA patients using an immunoassay, with their clinical and laboratory data reviewed. The optimal cut-off point of EN-RAGE and sRAGE was calculated by finding the threshold with the maximum sum of sensitivity and specificity. In addition, the least absolute shrinkage and selection operator regression was adopted to select variables included in the multivariable Cox proportional hazards (PH) regression model. Results: The median age of the patients was 67.0 years, and 34% were male. Neither serum EN-RAGE nor sRAGE at diagnosis was correlated with the Birmingham Vasculitis Activity Score. Furthermore, no correlation was observed between serum EN-RAGE and sRAGE. Deceased patients had significantly lower serum EN-RAGE and higher serum sRAGE at diagnosis compared to surviving patients. Patients with serum EN-RAGE at diagnosis ≤84.37 ng/mL and serum sRAGE at diagnosis ≥1.82 ng/mL showed significantly lower survival probabilities compared to those without. In multivariable Cox PH regression model, only serum sRAGE at diagnosis ≥1.82 ng/mL, rather than serum EN-RAGE at diagnosis ≤84.37 ng/mL, was independently associated with all-cause mortality (hazard ratio 7.094). Conclusion This study is the first to demonstrate that serum sRAGE at diagnosis may independently predict all-cause mortality during follow-up in patients with MPA and GPA.

Background and Objectives: Kawasaki disease (KD) is an acute vasculitis that primarily affects children under age 5 years. Approximately 20–25% of untreated children with KD and 3–5% of those treated with intravenous immunoglobulin therapy develop coronary artery aneurysms (CAAs). The prevalence of CAAs is much higher in male than in female patients with KD, but the underlying factors contributing to susceptibility to CAAs in patients with KD remain unclear. This study aimed to identify sex-specific susceptibility loci associated with CAAs in KD patients. Methods: A sex-stratified genome-wide association study (GWAS) was performed using previously obtained GWAS data from 296 KD patients and a new replication study in an independent set of 976 KD patients by comparing KD patients without CAA (controls) and KD patients with aneurysms (internal diameter ≥5 mm) (cases). Results: Six male-specific susceptibility loci, PDE1C, NOS3, DLG2, CPNE8, FUNDC1, and GABRQ (odds ratios [ORs], 2.25–9.98; p=0.00204–1.96×10−6 ), and 2 female-specific susceptibility loci, SMAD3 (OR, 4.59; p=0.00016) and IL1RAPL1 (OR, 4.35; p=0.00026), were significantly associated with CAAs in patients with KD. In addition, the numbers of CAA risk alleles additively contributed to the development of CAAs in patients with KD. Conclusions A sex-stratified GWAS identified 6 male-specific (PDE1C, NOS3, DLG2, CPNE8, FUNDC1, and GABRQ) and 2 female-specific (SMAD3 and IL1RAPL1) CAA susceptibility loci in patients with KD.

Objective: To compare the progression of muscle fibrosis of various site and its relation between cardiac deterioration in Duchenne muscular dystrophy (DMD). In this study aimed to examine the associations between echocardiogram-based cardiac function indices and fibrosis of the abdominal and lower extremity muscles in patients with DMD to facilitate early detection of cardiac dysfunction and identify its predictors. Methods: Twenty-one patients with DMD patients were enrolled in the study. The association between cardiac dysfunction and fibrosis of the abdominal and lower extremity muscles was determined by analyzing the echocardiography and elastography. Non-parametric Spearman rank correlation coefficients were used to examine the pairwise relationships between cardiac function and muscle elasticity. Results: All patients were male and non-ambulant. Their mean age was 18.45±4.28 years. The strain ratios of the abdominal muscle and quadriceps muscles were significantly higher than those of the medial gastrocnemius. The strain ratio of the rectus abdominis muscle has a significant negative correlation with left ventricular ejection fraction. Cardiac function and valvular insufficiency were not significantly correlated with muscle strain ratio. According to the result of our study, the only skeletal muscle which showed significant correlation with cardiac dysfunction was degree abdominal muscle fibrosis. Conclusion The degree of fibrosis of respiratory muscles was also significantly associated with cardiac dysfunction; therefore, it can be used as a predictor of cardiac dysfunction in patients with DMD in clinical practice.

Purpose: This study aimed to investigate whether the serum extracellular newly identified receptor for advanced glycation end products binding protein (EN-RAGE) and the soluble form of RAGE (sRAGE) measured at diagnosis are associated with all-cause mortality in patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). Materials and Methods: Serum EN-RAGE and sRAGE were measured in 75 immunosuppressive drug-naïve MPA and GPA patients using an immunoassay, with their clinical and laboratory data reviewed. The optimal cut-off point of EN-RAGE and sRAGE was calculated by finding the threshold with the maximum sum of sensitivity and specificity. In addition, the least absolute shrinkage and selection operator regression was adopted to select variables included in the multivariable Cox proportional hazards (PH) regression model. Results: The median age of the patients was 67.0 years, and 34% were male. Neither serum EN-RAGE nor sRAGE at diagnosis was correlated with the Birmingham Vasculitis Activity Score. Furthermore, no correlation was observed between serum EN-RAGE and sRAGE. Deceased patients had significantly lower serum EN-RAGE and higher serum sRAGE at diagnosis compared to surviving patients. Patients with serum EN-RAGE at diagnosis ≤84.37 ng/mL and serum sRAGE at diagnosis ≥1.82 ng/mL showed significantly lower survival probabilities compared to those without. In multivariable Cox PH regression model, only serum sRAGE at diagnosis ≥1.82 ng/mL, rather than serum EN-RAGE at diagnosis ≤84.37 ng/mL, was independently associated with all-cause mortality (hazard ratio 7.094). Conclusion This study is the first to demonstrate that serum sRAGE at diagnosis may independently predict all-cause mortality during follow-up in patients with MPA and GPA.

Purpose: This study aimed to investigate whether the serum extracellular newly identified receptor for advanced glycation end products binding protein (EN-RAGE) and the soluble form of RAGE (sRAGE) measured at diagnosis are associated with all-cause mortality in patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). Materials and Methods: Serum EN-RAGE and sRAGE were measured in 75 immunosuppressive drug-naïve MPA and GPA patients using an immunoassay, with their clinical and laboratory data reviewed. The optimal cut-off point of EN-RAGE and sRAGE was calculated by finding the threshold with the maximum sum of sensitivity and specificity. In addition, the least absolute shrinkage and selection operator regression was adopted to select variables included in the multivariable Cox proportional hazards (PH) regression model. Results: The median age of the patients was 67.0 years, and 34% were male. Neither serum EN-RAGE nor sRAGE at diagnosis was correlated with the Birmingham Vasculitis Activity Score. Furthermore, no correlation was observed between serum EN-RAGE and sRAGE. Deceased patients had significantly lower serum EN-RAGE and higher serum sRAGE at diagnosis compared to surviving patients. Patients with serum EN-RAGE at diagnosis ≤84.37 ng/mL and serum sRAGE at diagnosis ≥1.82 ng/mL showed significantly lower survival probabilities compared to those without. In multivariable Cox PH regression model, only serum sRAGE at diagnosis ≥1.82 ng/mL, rather than serum EN-RAGE at diagnosis ≤84.37 ng/mL, was independently associated with all-cause mortality (hazard ratio 7.094). Conclusion This study is the first to demonstrate that serum sRAGE at diagnosis may independently predict all-cause mortality during follow-up in patients with MPA and GPA.

Background and Objectives: Kawasaki disease (KD) is an acute vasculitis that primarily affects children under age 5 years. Approximately 20–25% of untreated children with KD and 3–5% of those treated with intravenous immunoglobulin therapy develop coronary artery aneurysms (CAAs). The prevalence of CAAs is much higher in male than in female patients with KD, but the underlying factors contributing to susceptibility to CAAs in patients with KD remain unclear. This study aimed to identify sex-specific susceptibility loci associated with CAAs in KD patients. Methods: A sex-stratified genome-wide association study (GWAS) was performed using previously obtained GWAS data from 296 KD patients and a new replication study in an independent set of 976 KD patients by comparing KD patients without CAA (controls) and KD patients with aneurysms (internal diameter ≥5 mm) (cases). Results: Six male-specific susceptibility loci, PDE1C, NOS3, DLG2, CPNE8, FUNDC1, and GABRQ (odds ratios [ORs], 2.25–9.98; p=0.00204–1.96×10−6 ), and 2 female-specific susceptibility loci, SMAD3 (OR, 4.59; p=0.00016) and IL1RAPL1 (OR, 4.35; p=0.00026), were significantly associated with CAAs in patients with KD. In addition, the numbers of CAA risk alleles additively contributed to the development of CAAs in patients with KD. Conclusions A sex-stratified GWAS identified 6 male-specific (PDE1C, NOS3, DLG2, CPNE8, FUNDC1, and GABRQ) and 2 female-specific (SMAD3 and IL1RAPL1) CAA susceptibility loci in patients with KD.

Objective: To compare the progression of muscle fibrosis of various site and its relation between cardiac deterioration in Duchenne muscular dystrophy (DMD). In this study aimed to examine the associations between echocardiogram-based cardiac function indices and fibrosis of the abdominal and lower extremity muscles in patients with DMD to facilitate early detection of cardiac dysfunction and identify its predictors. Methods: Twenty-one patients with DMD patients were enrolled in the study. The association between cardiac dysfunction and fibrosis of the abdominal and lower extremity muscles was determined by analyzing the echocardiography and elastography. Non-parametric Spearman rank correlation coefficients were used to examine the pairwise relationships between cardiac function and muscle elasticity. Results: All patients were male and non-ambulant. Their mean age was 18.45±4.28 years. The strain ratios of the abdominal muscle and quadriceps muscles were significantly higher than those of the medial gastrocnemius. The strain ratio of the rectus abdominis muscle has a significant negative correlation with left ventricular ejection fraction. Cardiac function and valvular insufficiency were not significantly correlated with muscle strain ratio. According to the result of our study, the only skeletal muscle which showed significant correlation with cardiac dysfunction was degree abdominal muscle fibrosis. Conclusion The degree of fibrosis of respiratory muscles was also significantly associated with cardiac dysfunction; therefore, it can be used as a predictor of cardiac dysfunction in patients with DMD in clinical practice.

Background and Objectives: Kawasaki disease (KD) is an acute vasculitis that primarily affects children under age 5 years. Approximately 20–25% of untreated children with KD and 3–5% of those treated with intravenous immunoglobulin therapy develop coronary artery aneurysms (CAAs). The prevalence of CAAs is much higher in male than in female patients with KD, but the underlying factors contributing to susceptibility to CAAs in patients with KD remain unclear. This study aimed to identify sex-specific susceptibility loci associated with CAAs in KD patients. Methods: A sex-stratified genome-wide association study (GWAS) was performed using previously obtained GWAS data from 296 KD patients and a new replication study in an independent set of 976 KD patients by comparing KD patients without CAA (controls) and KD patients with aneurysms (internal diameter ≥5 mm) (cases). Results: Six male-specific susceptibility loci, PDE1C, NOS3, DLG2, CPNE8, FUNDC1, and GABRQ (odds ratios [ORs], 2.25–9.98; p=0.00204–1.96×10−6 ), and 2 female-specific susceptibility loci, SMAD3 (OR, 4.59; p=0.00016) and IL1RAPL1 (OR, 4.35; p=0.00026), were significantly associated with CAAs in patients with KD. In addition, the numbers of CAA risk alleles additively contributed to the development of CAAs in patients with KD. Conclusions A sex-stratified GWAS identified 6 male-specific (PDE1C, NOS3, DLG2, CPNE8, FUNDC1, and GABRQ) and 2 female-specific (SMAD3 and IL1RAPL1) CAA susceptibility loci in patients with KD.

Purpose: This study aimed to investigate whether the serum extracellular newly identified receptor for advanced glycation end products binding protein (EN-RAGE) and the soluble form of RAGE (sRAGE) measured at diagnosis are associated with all-cause mortality in patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). Materials and Methods: Serum EN-RAGE and sRAGE were measured in 75 immunosuppressive drug-naïve MPA and GPA patients using an immunoassay, with their clinical and laboratory data reviewed. The optimal cut-off point of EN-RAGE and sRAGE was calculated by finding the threshold with the maximum sum of sensitivity and specificity. In addition, the least absolute shrinkage and selection operator regression was adopted to select variables included in the multivariable Cox proportional hazards (PH) regression model. Results: The median age of the patients was 67.0 years, and 34% were male. Neither serum EN-RAGE nor sRAGE at diagnosis was correlated with the Birmingham Vasculitis Activity Score. Furthermore, no correlation was observed between serum EN-RAGE and sRAGE. Deceased patients had significantly lower serum EN-RAGE and higher serum sRAGE at diagnosis compared to surviving patients. Patients with serum EN-RAGE at diagnosis ≤84.37 ng/mL and serum sRAGE at diagnosis ≥1.82 ng/mL showed significantly lower survival probabilities compared to those without. In multivariable Cox PH regression model, only serum sRAGE at diagnosis ≥1.82 ng/mL, rather than serum EN-RAGE at diagnosis ≤84.37 ng/mL, was independently associated with all-cause mortality (hazard ratio 7.094). Conclusion This study is the first to demonstrate that serum sRAGE at diagnosis may independently predict all-cause mortality during follow-up in patients with MPA and GPA.

Objective: To compare the progression of muscle fibrosis of various site and its relation between cardiac deterioration in Duchenne muscular dystrophy (DMD). In this study aimed to examine the associations between echocardiogram-based cardiac function indices and fibrosis of the abdominal and lower extremity muscles in patients with DMD to facilitate early detection of cardiac dysfunction and identify its predictors. Methods: Twenty-one patients with DMD patients were enrolled in the study. The association between cardiac dysfunction and fibrosis of the abdominal and lower extremity muscles was determined by analyzing the echocardiography and elastography. Non-parametric Spearman rank correlation coefficients were used to examine the pairwise relationships between cardiac function and muscle elasticity. Results: All patients were male and non-ambulant. Their mean age was 18.45±4.28 years. The strain ratios of the abdominal muscle and quadriceps muscles were significantly higher than those of the medial gastrocnemius. The strain ratio of the rectus abdominis muscle has a significant negative correlation with left ventricular ejection fraction. Cardiac function and valvular insufficiency were not significantly correlated with muscle strain ratio. According to the result of our study, the only skeletal muscle which showed significant correlation with cardiac dysfunction was degree abdominal muscle fibrosis. Conclusion The degree of fibrosis of respiratory muscles was also significantly associated with cardiac dysfunction; therefore, it can be used as a predictor of cardiac dysfunction in patients with DMD in clinical practice.