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.

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.

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.

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.

Background: The benefits of transradial access (TRA) over transfemoral access (TFA) for bifurcation percutaneous coronary intervention (PCI) are uncertain because of the limited availability of device selection. This study aimed to compare the procedural differences and the in-hospital and long-term outcomes of TRA and TFA for bifurcation PCI using secondgeneration drug-eluting stents (DESs). Methods: Based on data from the Coronary Bifurcation Stenting Registry III, a retrospective registry of 2,648 patients undergoing bifurcation PCI with second-generation DES from 21 centers in South Korea, patients were categorized into the TRA group (n = 1,507) or the TFA group (n = 1,141). After propensity score matching (PSM), procedural differences, in-hospital outcomes, and device-oriented composite outcomes (DOCOs; a composite of cardiac death, target vessel-related myocardial infarction, and target lesion revascularization) were compared between the two groups (772 matched patients each group). Results: Despite well-balanced baseline clinical and lesion characteristics after PSM, the use of the two-stent strategy (14.2% vs. 23.7%, P = 0.001) and the incidence of in-hospital adverse outcomes, primarily driven by access site complications (2.2% vs. 4.4%, P = 0.015), were significantly lower in the TRA group than in the TFA group. At the 5-year follow-up, the incidence of DOCOs was similar between the groups (6.3% vs. 7.1%, P = 0.639). Conclusion The findings suggested that TRA may be safer than TFA for bifurcation PCI using second-generation DESs. Despite differences in treatment strategy, TRA was associated with similar long-term clinical outcomes as those of TFA. Therefore, TRA might be the preferred access for bifurcation PCI using second-generation DES.

Background: There is still unmet need in treating neuropathic pain and increasing awareness regarding the use of drug combinations to increase the effectiveness of treatment and reduce adverse effects in patients with neuropathic pain. Methods: This study was performed to determine the individual and combined effects of pregabalin, tianeptine, and clopidogrel in a rat model of neuropathic pain.The model was created by ligation of the L5-L6 spinal nerve in male Sprague–Dawley rats; mechanical allodynia was confirmed using von Frey filaments. Drugs were administered to the intrathecal space and mechanical allodynia was assessed; drug interactions were estimated by isobolographic or fixed-dose analyses. Results: Intrathecal pregabalin and tianeptine increased the mechanical withdrawal threshold in a dose-dependent manner, but intrathecal clopidogrel had little effect on the mechanical withdrawal threshold. An additive effect was noted between pregabalin and tianeptine, but not between pregabalin and clopidogrel. Conclusions These findings suggest that intrathecal coadministration of pregabalin and tianeptine effectively attenuated mechanical allodynia in the rat model of neuropathic pain. Thus, pregabalin plus tianeptine may be a valid option to enhance the efficacy of neuropathic pain treatment.

Background and Objectives: Kawasaki disease (KD) is an acute systemic vasculitis that affects the coronary arteries. Abnormal immune reactions are thought to contribute to disease pathogenesis. The effect of immunoglobulin (Ig) isotype (IgG, IgA, IgM, and IgE) on inflammatory data and clinical outcomes of patients with KD was examined. Methods: Ig levels in 241 patients with KD were measured during the acute, subacute, convalescent, and normal phases of the disease. Results: Compared with reference Ig values, IgG, IgA, and IgM levels were significantly higher in the subacute phase, while IgE levels were elevated in 73.9% (178/241) of patients with KD in all clinical phases. However, high IgE levels were not associated with clinical outcomes, including intravenous immunoglobulin unresponsiveness and coronary artery lesions (CALs).Significantly more CALs were observed in the high IgA group than in the normal IgA group (44.7% vs. 20.8%, respectively; p<0.01). In addition, IgA levels in the acute phase (p=0.038) were 2.2-fold higher, and those in the subacute phase were 1.7-fold higher (p <0.001), in the CAL group than in the non-CAL group. IgA concentrations increased along with the size of the coronary artery aneurysm (p <0.001). Furthermore, there was a strong correlation between IgA levels and CAL size (r=0.435, p<0.001), with a high odds ratio of 2.58 (p=0.022). Conclusions High IgA levels in patients with KD are prognostic for the risk of CALs.

Kawasaki disease (KD) is an acute pediatric vasculitis that affects genetically susceptible infants and children. To identify coding variants that influence susceptibility to KD, we conducted whole exome sequencing of 159 patients with KD and 902 controls, and performed a replication study in an independent 586 cases and 732 controls. We identified five rare coding variants in five genes (FCRLA, PTGER4, IL17F, CARD11, and SIGLEC10) associated with KD (odds ratio [OR], 1.18–4.41; p = 0.0027–0.031). We also performed association analysis in 26 KD patients with coronary artery aneurysms (CAAs; diameter > 5 mm) and 124 patients without CAAs (diameter < 3 mm), and identified another five rare coding variants in five genes (FGFR4, IL31RA, FNDC1, MMP8, and FOXN1), which may be associated with CAA (OR, 3.89–37.3; p = 0.0058–0.0261). These results provide insights into new candidate genes and genetic variants potentially involved in the development of KD and CAA.

Background and Objectives: Kawasaki disease (KD) is an acute systemic vasculitis that affects the coronary arteries. Abnormal immune reactions are thought to contribute to disease pathogenesis. The effect of immunoglobulin (Ig) isotype (IgG, IgA, IgM, and IgE) on inflammatory data and clinical outcomes of patients with KD was examined. Methods: Ig levels in 241 patients with KD were measured during the acute, subacute, convalescent, and normal phases of the disease. Results: Compared with reference Ig values, IgG, IgA, and IgM levels were significantly higher in the subacute phase, while IgE levels were elevated in 73.9% (178/241) of patients with KD in all clinical phases. However, high IgE levels were not associated with clinical outcomes, including intravenous immunoglobulin unresponsiveness and coronary artery lesions (CALs).Significantly more CALs were observed in the high IgA group than in the normal IgA group (44.7% vs. 20.8%, respectively; p<0.01). In addition, IgA levels in the acute phase (p=0.038) were 2.2-fold higher, and those in the subacute phase were 1.7-fold higher (p <0.001), in the CAL group than in the non-CAL group. IgA concentrations increased along with the size of the coronary artery aneurysm (p <0.001). Furthermore, there was a strong correlation between IgA levels and CAL size (r=0.435, p<0.001), with a high odds ratio of 2.58 (p=0.022). Conclusions High IgA levels in patients with KD are prognostic for the risk of CALs.

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a major side effect of anti-cancer drugs. Neurotensin receptors (NTSRs) are widely distributed within the pain circuits in the central nervous system. The purpose of this study was to determine the role of NTSR1 by examining the effects of an NTSR1 agonist in rats with CIPN and investigate the contribution of spinal serotonin receptors to the antinociceptive effect. Methods: Sprague–Dawley rats (weight 150–180 g) were used in this study. CIPN was induced by injecting cisplatin (2 mg/kg) once a day for 4 days. Intrathecal catheters were placed into the subarachnoid space of the CIPN rats. The antiallodynic effects of intrathecally or intraperitoneally administered PD 149163, an NTSR1 agonist, were evaluated. Furthermore, the levels of serotonin in the spinal cord were measured by high-performance liquid chromatography. Results: Intrathecal or intraperitoneal PD 149163 increased the paw withdrawal threshold in CIPN rats. Intrathecal administration of the NTSR1 antagonist SR 48692 suppressed the antinociceptive effect of PD 149163 given via the intrathecal route, but not the antinociceptive effect of intraperitoneally administered PD 149163. Intrathecal administration of dihydroergocristine, a serotonin receptor antagonist, suppressed the antinociceptive effect of intrathecally administered, but not intraperitoneally administered, PD 149163. Injecting cisplatin diminished the serotonin level in the spinal cord, but intrathecal or intraperitoneal administration of PD 149163 did not affect this reduction. Conclusions NTSR1 played a critical role in modulating CIPN-related pain. Therefore, NTSR1 agonists may be useful therapeutic agents to treat CIPN. In addition, spinal serotonin receptors may be indirectly involved in the effect of NTSR1 agonist.