Shear wave elastography and dispersion imaging for hepatic veno-occlusive disease prediction after pediatric hematopoietic stem cell transplantation: a feasibility study.

BACKGROUND: Non-invasive imaging modalities are warranted for diagnosing and monitoring veno-occlusive disease because early diagnosis and treatment improve the prognosis. OBJECTIVE: To evaluate the usefulness of liver shear wave elastography (SWE) and shear wave dispersion (SWD) imaging in diagnosing and monitoring veno-occlusive disease in pediatric patients. MATERIALS AND METHODS: We conducted a prospective cohort study at a single tertiary hospital from March 2021 to April 2022. The study protocol included four ultrasound (US) sessions: a baseline US and three follow-up US after hematopoietic stem cell transplantation. Clinical criteria, including the European Society for Blood and Marrow Transplantation criteria, were used to diagnose veno-occlusive disease. We compared clinical factors and US parameters between the veno-occlusive disease and non-veno-occlusive disease groups. The diagnostic performance of US parameters for veno-occlusive disease was assessed by plotting receiver operating characteristic (ROC) curves. We describe temporal changes in US parameters before and after veno-occlusive disease diagnosis. RESULTS: Among the 38 participants (mean age 10.7 years), eight developed veno-occlusive disease occurring 17.0 ± 5.2 days after hematopoietic stem cell transplantation. Liver stiffness, as measured by SWE (15.0 ± 6.2 kPa vs. 5.8 ± 1.8 kPa; P<0.001), and viscosity, as assessed with SWD (17.7 ± 3.1 m/s/kHz vs. 14.3 ± 2.8 m/s/kHz; P=0.015), were significantly higher in the veno-occlusive disease group compared to the non-veno-occlusive disease group at the time of diagnosis. Liver stiffness demonstrated the highest area under the ROC (AUROC) curves at 0.960, with an optimal predictive value of >6.5 kPa, resulting in sensitivity and specificity of 100% and 83.3%, respectively. Viscosity demonstrated an AUROC of 0.783, with an optimal cutoff value of 13.9 m/s/kHz for predicting veno-occlusive disease, with a sensitivity of 100% and specificity of 53.3%, respectively. Liver stiffness increased with disease severity and decreased during post-treatment follow-up. CONCLUSION: SWE may be a promising technique for early diagnosis and severity prediction of veno-occlusive disease. Furthermore, liver viscosity assessed by SWD may serve as an additional marker of veno-occlusive disease.

Congenital heart disease at Laos Children's Hospital: Two year experience.

BACKGROUND: Management of congenital heart disease (CHD) in developing countries is challenging because of limited access to health-care facilities and socioeconomic limitations. The aim of this study was to describe the recent experience with CHD at Children's Hospital, Vientiane, Laos, the only pediatric referral hospital in the country. METHODS: From July 2013 to November 2015, 1009 echocardiograms were carried out in 797 individuals who visited Children's Hospital, in whom CHD was identified in 213. Demographic characteristics, echocardiography and age at first CHD diagnosis on echocardiogram were compared by residential area. RESULTS: Among the 213 patients, the most frequent anomalies, in descending order, were ventricular septal defect, atrial septal defect, patent ductus arteriosus, and tetralogy of Fallot. Moderate or severe CHD requiring surgery or intervention was detected in 137 patients; median age at initial diagnosis was 6.0 months (IQR, 1.5-29.8). Among those with moderate or severe CHD, 89 patients were from rural areas and 48 from the capital area. The proportion of patients from rural areas older than 1 and 3 years at diagnosis was 46.1% and 32.6%, respectively. In contrast, patients from the capital area were diagnosed at a significantly earlier age: 16.7% at age >1 year and 6.2% at age >3 years (both P < 0.001 vs rural areas). CONCLUSIONS: Diagnosis of CHD requiring surgery is delayed in Laos, especially in rural areas. Better education and training of local medical staff, and greater access to medical advice are required to improve CHD care in Laos.

Impaired Osteogenesis of Disease-Specific Induced Pluripotent Stem Cells Derived from a CFC Syndrome Patient.

Cardiofaciocutaneous (CFC) syndrome is a rare genetic disorder caused by mutations in the extracellular signal-regulated kinase (ERK) signaling. However, little is known about how aberrant ERK signaling is associated with the defective bone development manifested in most CFC syndrome patients. In this study, induced pluripotent stem cells (iPSCs) were generated from dermal fibroblasts of a CFC syndrome patient having rapidly accelerated fibrosarcoma kinase B (BRAF) gain-of-function mutation. CFC-iPSCs were differentiated into mesenchymal stem cells (CFC-MSCs) and further induced to osteoblasts in vitro. The osteogenic defects of CFC-MSCs were revealed by alkaline phosphatase activity assay, mineralization assay, quantitative real-time polymerase chain reaction (qRT-PCR), and western blotting. Osteogenesis of CFC-MSCs was attenuated compared to wild-type (WT)-MSCs. In addition to activated ERK signaling, increased p-SMAD2 and decreased p-SMAD1 were observed in CFC-MSCs during osteogenesis. The defective osteogenesis of CFC-MSCs was rescued by inhibition of ERK signaling and SMAD2 signaling or activation of SMAD1 signaling. Importantly, activation of ERK signaling and SMAD2 signaling or inhibition of SMAD1 signaling recapitulated the impaired osteogenesis in WT-MSCs. Our findings indicate that SMAD2 signaling and SMAD1 signaling as well as ERK signaling are responsible for defective early bone development in CFC syndrome, providing a novel insight on the pathological mechanism and therapeutic targets.

Enhanced SMAD1 Signaling Contributes to Impairments of Early Development in CFC-iPSCs.

Cardio-facio-cutaneous (CFC) syndrome is a developmental disorder caused by constitutively active ERK signaling manifesting mainly from BRAF mutations. Little is known about the role of elevated ERK signaling in CFC syndrome during early development. Here, we show that both SMAD1 and ERK signaling pathways may contribute to the developmental defects in CFC syndrome. Induced pluripotent stem cells (iPSCs) derived from dermal fibroblasts of a CFC syndrome patient (CFC-iPSCs) revealed early developmental defects in embryoid body (EB) development, ß-catenin localization, and neuronal differentiation. Both SMAD1 and ERK signalings were significantly activated in CFC-iPSCs during EB formation. Most of the ß-catenin was dissociated from the membrane and preferentially localized into the nucleus in CFC-EBs. Furthermore, activation of SMAD1 signaling recapitulated early developmental defects in wild-type iPSCs. Intriguingly, inhibition of SMAD1 signaling in CFC-iPSCs rescued aberrant EB morphology, impaired neuronal differentiation, and altered ß-catenin localization. These results suggest that SMAD1 signaling may be a key pathway contributing the pathogenesis of CFC syndrome during early development.

Hepatobiliary risk factors for clinical outcome of Kawasaki disease in children.

BACKGROUND: Kawasaki disease (KD) is an acute febrile vasculitis that causes coronary artery abnormality (CAA) as a complication. In some patients, an association has been noted between elevated liver enzymes or an abnormal gallbladder (GB) and hepatobiliary involvement in KD. In this study, we aimed to evaluate clinical, laboratory, and ultrasonographic (USG) risk factors of hepatobiliary involvement for the intravenous immunoglobulin (IVIG) resistance and the development of CAA in children with KD. METHODS: From March 2004 through January 2013, clinical features, laboratory data, echocardiographic findings, and USG findings were retrospectively reviewed regarding the response to IVIG treatment and coronary artery complications in 67 children with KD. Acute acalculous cholecystitis (AAC) was diagnosed based on USG criteria. RESULTS: Among all factors, only the prothrombin time international normalized ratio was significantly different between the IVIG-response and IVIG-resistance groups (p = 0.024). CAA was statistically more frequent in the AAC group (n = 24) than in the non-AAC group (n = 43) (23.3% vs. 58.3%, p = 0.019). Among the laboratory factors, segmented neutrophil percentage, total bilirubin level, and C-reactive protein were significant in children with CAA (p = 0.014, p = 0.009, and p = 0.010). Abnormal GB findings on USG were significantly more frequent in children with CAA than in those without CAA (p = 0.007; OR = 4.620; 95% confidence interval [CI]: 1.574-13.558). GB distension on USG was the only significant risk factor for CAA (p = 0.001; OR = 7.288; 95% CI: 2.243-23.681) by using multiple logistic regression analysis. CONCLUSION: For children in the acute phase of KD, USG findings of the GB, especially GB distension, may be an important risk factor for CAA as a complication.

Prevalence of congenital heart defects associated with Down syndrome in Korea.

Congenital heart defect (CHD) is common in infants with Down syndrome (DS), which is the principle cause of mortality. However, there is no data available for the frequency and types of CHD in infants with DS in Korea. We investigated the frequency of CHD in infants with DS in Korea. After the survey on birth defects was conducted throughout the country, the prevalence of CHD in DS in 2005-2006 was calculated. This study was conducted based on the medical insurance claims database of the National Health Insurance Corporation. The number of total births in Korea was 888,263 in 2005-2006; of them, 25,975 cases of birth defects were identified. The prevalence of DS was 4.4 per 10,000 total births, accounting for 1.5% of all birth defects. Of the 394 infants with DS, 224 (56.9%) had a CHD. Atrial septal defect was the most common defect accounting for 30.5% of DS followed by ventricular septal defect (19.3%), patent duct arteriosus (17.5%), and atrioventricular septal defect (9.4%). Our study will be helpful to demonstrate the current status of DS and to identify the distribution of CHD in infants with DS in Korea.

Radiofrequency catheter ablation for supraventricular tachycardia: a comparison study of children aged 0-4 and 5-9 years.

BACKGROUND: The safety and effectiveness of radiofrequency catheter ablation (RFCA) for supraventricular tachycardia (SVT) in young children was investigated. METHODS: Ninety-five children who underwent RFCA procedures were stratified according to age (group 1, 0-4 years, n = 24; group 2, 5-9 years, n = 71) and were evaluated retrospectively. RESULTS: Among the 95 patients, atrioventricular reentrant tachycardia was 78.9%, atrioventricular nodal reentrant tachycardia was 10.5%, and ectopic atrial tachycardia was 8.4%. The acute success rate of RFCA was 97.9% and the recurrence rate was 11.6%. RFCA was performed for different main reasons in each group, including drug-resistant tachycardia (37.5% in group 1 vs 7% in group 2; P = 0.001) and symptomatic tachycardia (4.2% in group 1 vs 57.7% in group 2; P < 0.001). There was no significant difference in success rate, recurrence rate, and procedure and fluoroscopy duration between the two groups. The acute success rates did not differ significantly between patients with a single accessory pathway (AP) and those with multiple APs; however, failure or recurrence was more common in the patients with multiple APs (38.5% vs 11.5%; P = 0.01). The multiple APs were found frequently on the right side (P = 0.005). Septal dyskinesia with left ventricular dysfunction in Wolff-Parkinson-White syndrome and tachycardia-induced cardiomyopathy improved after RFCA. CONCLUSIONS: RFCA was found to be effective and safe for SVT in young children.

Sudden cardiac arrest during anesthesia in a 30-month-old boy with syndactyly: a case of genetically proven Timothy syndrome.

Timothy syndrome, long QT syndrome type 8, is highly malignant with ventricular tachyarrhythmia. A 30-month-old boy had sudden cardiac arrest during anesthesia induction before plastic surgery for bilateral cutaneous syndactyly. After successful resuscitation, prolonged QT interval (QTc, 0.58-0.60 sec) and T-wave alternans were found in his electrocardiogram. Starting ß-blocker to prevent further tachycardia and collapse event, then there were no more arrhythmic events. The genes KCNQ1, KCNH2, KCNE1 and 2, and SCN5A were negative for long QT syndrome. The mutation p.Gly406Arg was confirmed in CACNA1C, which maintains L-type calcium channel depolarization in the heart and other systems.

Prevalence of birth defects in Korean livebirths, 2005-2006.

We investigated the livebirths prevalence and occurrence pattern of birth defects in Korea. After the survey on birth defects was done in 2,348 medical institutions around the nation, the birth defect prevalence of livebirths in 2005-2006 was calculated. This study was based on the medical insurance claims database of the National Health Insurance Corporation. The number of livebirths in Korea was 883,184 from 2005-2006, and 25,335 cases of birth defects were notified to our study, equivalent to a prevalence of 286.9 per 10,000 livebirths. Anomalies of the circulatory system were the most common defects, accounting for 43.4% of birth defects with a prevalence of 124.5 per 10,000 livebirths. It was followed by the musculoskeletal system anomalies, the digestive system anomalies, and the urinary system anomalies. The five major birth defects based on the ranking of prevalence were atrial septal defect, ventricular septal defect, hydronephrosis, patent ductus arteriosus, and cleft lip/palate. Birth defects in livebirths were associated with a high proportion of low birthweight, prematurity, multiple births and advanced maternal age. The prevalence of birth defects in Korea is similar to or lower than those reported in developed countries. Our study suggests baseline data to explain the current status of birth defects and to establish a registry system of birth defects in Korea.

Clinical significance of thrombosis in an intracardiac blind pouch after a Fontan operation.

The univentricular heart after the Fontan operation may have a blind pouch formed by the pulmonary stump or rudimentary ventricle according to the anatomy before surgery. Thrombosis in an intracardiac blind pouch of patients with a univentricular heart is a hazardous complication. Because only a few reports have described this complication, the authors evaluated the clinical significance of thrombosis in an intracardiac blind pouch of a univentricular heart. They performed a retrospective review of medical records from August 1986 to December 2007. Four patients were confirmed as having thrombosis in a pulmonary artery stump and one patient as having thrombosis in a rudimentary ventricle shown by cardiac computed tomography (CT). This represents 1.85% (5/271) of patients with ongoing regular follow-up evaluation after the Fontan operation. The median age at diagnosis was 14.2 years. Two of the five patients were taking aspirin and one patient was taking warfarin when they were identified for the development of thrombosis. None of the patients demonstrated thrombosis in the Fontan tract or venous side of the circulation. Brain magnetic resonance imaging (MRI) showed that three patients had cerebral infarction and one patient had suggestive old ischemia. Three patients with thrombus in the pulmonary stump underwent pulmonary artery stump thrombectomy and pulmonary valve obliteration. One patient with thrombus in the rudimentary ventricle underwent ventricular septal defect (VSD) closure with thrombectomy. Thrombus in a blind pouch could cause systemic thromboembolism despite little blood communication. Therefore, surgical modification of the pulmonary stump and VSD closure of the rudimentary ventricle are required to reduce the risk of later thrombus formation. Clinicians should not overlook the possibility of thrombus in a ligated pulmonary artery stump or a rudimentary ventricle after the Fontan operation, which may increase the risk of embolic stroke for patients with single-ventricle physiology.

Chronic total occlusion by stent fracture in Kawasaki disease: is recanalisation possible?

Despite various medications for Kawasaki disease, a small number of children have been undergoing interventions for severe coronary artery complications. Transcatheter intervention is a feasible alternative to coronary artery bypass grafting in a patient with chronic totally occluded lesion after Kawasaki disease, even by stent fracture.

Significance of circulating hepatocyte growth factor in protein-losing enteropathy after Fontan operation.

The purpose of this study was to measure serum hepatocyte growth factor (HGF) and elucidate the relationship between HGF and protein-losing enteropathy (PLE) after Fontan operation (FO). Ten patients with PLE (mean age 15.7 ± 8.7 years) who underwent FO were enrolled. Control group 1 comprised 20 patients without PLE after FO, and control group 2 comprised 10 patients with nephrotic syndrome (NS). Serum HGF, vascular endothelial growth factor, albumin, and random stool alpha-1 antitrypsin concentration were measured. Transthoracic echocardiography was completed. Serum HGF level was significantly greater in the PLE patients (0.61 ± 0.27 ng/ml) after FO than in the two control groups (0.41 ± 0.12 ng/ml [P = 0.024] for the Fontan group without PLE and 0.26 ± 0.12 ng/ml [P = 0.002] for the patients with NS). Serum albumin of patients with PLE (2.82 ± 0.96 g/dl) showed significantly lower levels compared with those of patients without PLE after FO (4.30 ± 0.37 g/dl, P < 0.001) but significantly greater levels compared with patients with NS (1.91 ± 0.33 g/dl, P = 0.019). Patients with greater serum HGF levels showed significant correlation with lower serum albumin level (P = 0.006, r = -0.495). Because serum HGF levels were significantly greater in patients with PLE after FO, HGF may play a role in the development of PLE after FO.

Septal dyskinesia and global left ventricular dysfunction in pediatric Wolff-Parkinson-White syndrome with septal accessory pathway.

INTRODUCTION: Echocardiographic studies have shown that some patients with Wolff-Parkinson-White (WPW) syndrome have myocardial dyskinesia in the segments precociously activated by an accessory pathway (AP). The aim of the present study was to determine the extent to which the AP contributes to global left ventricular (LV) dysfunction. METHODS: Electrophysiological and echocardiographic data from 62 children with WPW (age at diagnosis = 5.9 +/- 4.2 years) were retrospectively analyzed. RESULTS: The left ventricular ejection fraction (LVEF) of patients with septal APs (53 +/- 11%) was significantly lower than that of patients with right (62 +/- 5%) or left (61 +/- 4%) APs (P = 0.001). Compared to patients with normal septal motion (n = 56), patients with septal dyskinesia (n = 6) had a reduced LVEF (61 +/- 4% and 42 +/- 5%, respectively) and an increased LV end diastolic dimension (P < 0.001 for both comparisons). Multivariate analysis identified septal dyskinesia as the only significant risk factor for reduced LVEF. All 6 patients with septal dyskinesia had right septal APs, and a preexcited QRS duration that was longer than that of patients with normal septal motion (140 +/- 18 ms and 113 +/- 32 ms, respectively; P = 0.045). After RFA there were improvements in both intraventricular dyssynchrony (septal-to-posterior wall motion delay, from 154 +/- 91 ms to 33 +/- 17 ms) and interventricular septal thinning (from 3.0 +/- 0.5 mm to 5.3 +/- 2.6 mm), and a significant increase in LVEF (from 42 +/- 5% to 67 +/- 8%; P = 0.001). CONCLUSION: The dyskinetic segment activated by a right septal AP in WPW syndrome may lead to ventricular dilation and dysfunction. RFA produced mechanical resynchronization, reverse remodeling, and improvements in LV function.

Clinical spectrum and prognostic factors of pediatric ventricular tachycardia.

BACKGROUND: There have been no studies on the clinical characteristics and prognostic factors of pediatric ventricular tachycardia (VT). METHODS AND RESULTS: Eighty-one patients with pediatric VT were studied retrospectively at a single center. The median follow-up period was 6.0 years (0.7-23.5 years). Patients were categorized into 6 groups: idiopathic VT (IVT, n=37), catecholaminergic polymorphic VT (CPVT, n=10), congenital heart disease-associated VT (n=15), myocarditis-associated VT (n=8), cardiomyopathy-associated VT (CMP-VT, n=5) and miscellaneous. The age distribution of VT had 2 peaks (infant and teenager). VT with left bundle branch block configuration was more frequently nonsustained than VT with right bundle branch block configuration (61% vs 8%). Although 22% were asymptomatic, 38% experienced syncope or seizure and 16% had cardiac arrest. The overall mortality rate was 7.4%. The expected life span without cardiac arrest was <4 years in the CMP-VT group and the 10-year survival rate in CPVT patients was approximately 55%. Onset at infancy, monomorphic type and transcatheter/surgical ablation were related to the successful resolution of VT. Logistic regression analysis revealed that CPVT, CMP-VT, polymorphic VT and sustained VT were significantly correlated with death or cardiac arrest. CONCLUSIONS: The clinical features and prognosis of pediatric VT differed with the VT type, clinical categories and onset age. Accurate diagnosis and proper treatment according to the clinical categories may improve the outcome.

Dexrazoxane for preventing anthracycline cardiotoxicity in children with solid tumors.

This study attempted to assess the incidence and outcome of anthracycline cardiotoxicity and the role of dexrazoxane as a cardioprotectant in childhood solid tumors. The dexrazoxane group included 47 patients and the control group of historical cohort included 42. Dexrazoxane was given in the 10:1 ratio to doxorubicin. Fractional shortening and systolic and diastolic left ventricular diameters were used to assess the cardiac function. The median follow-ups were 54 months in the dexrazoxane group and 86 months in the control group. The mean cumulative doses of doxorubicin were 280.8+/-83.4 mg/m(2) in the dexrazoxane group and 266.1+/-75.0 mg/m(2) in the control group. The dexrazoxane group experienced significantly fewer cardiac events (27.7% vs. 52.4%) and less severe congestive heart failure (6.4% vs. 14.3%) than the control group. Thirteen cardiotoxicities including one cardiac death and 2 congestive heart failures occurred in the dexrazoxane group, and 22 cardiotoxicities including 2 cardiac deaths and 4 congestive heart failures, in the control group. Five year cardiac event free survival rates were 69.2% in the dexrazoxane group and 45.8% in the control group (P=0.04). Dexrazoxane reduces the incidence and severity of early and late anthracycline cardiotoxicity in childhood solid tumors.

Comparison of Union Rates Between Autogenous Iliac Crest Bone Graft and Local Bone Graft as Fusion Materials in Lumbar Fusion Surgery: An Evaluation of Up to 3-Level Fusion.

OBJECTIVE: To compare the radiologic union rates between autogenous iliac crest bone graft (ICBG) and local bone graft in 1- to 3-level lumbar fusion. METHODS: We reviewed 178 consecutive patients who underwent 1- to 3-level lumbar fusion surgery because of lumbar spinal stenosis. Fusion status of the anterior or posterior column was evaluated by plain radiographs obtained at 24 months postoperatively. If at least either the anterior or posterior column was fused, that segment was regarded as having achieved fusion and was termed segment union. The definition of overall union was achieving union of all segments in a single patient. RESULTS: For each ICBG group and local bone graft group, fusion rate of the anterior and posterior column, and rate of the segments and overall union at postoperative 2 years were not different between the groups, regardless of surgery level. In the overall union rate according to the fusion level, the ICBG group showed constant overall fusion rate according to the fusion level (i.e., 96.9%, 96.9%, and 93.1% for 1-, 2-, and 3-level fusion), but tended to decrease with increasing level in the local bone graft group (100%, 95.8%, and 85.7% for 1-, 2-, and 3-level fusion, respectively) without statistically significant differences. CONCLUSIONS: The union rate of 3-level fusion was not inferior to those of 1- or 2-level fusion in both ICBG and local bone graft patients. Local bone graft could be regarded as an adequate option for not only 1- or 2-level lumbar fusion but also 3-level lumbar fusion surgery.

Clinical Characteristics of Primary and Secondary Osteoporotic Fractures: Data from Single Referral Center Emergency Department.

BACKGROUND: To investigate the characteristics of patients with osteoporotic fractures (OF) who visited the emergency room, we analyzed the frequency and distribution of primary and secondary OF. METHODS: From March 2015 to April 2017, 406 patients with OF were assigned to wrist (W; n=132), spine (S; n=78), and hip (H; n=196) according to the site. All subjects were classified as having primary fracture or secondary fracture. Age, fracture site, the risk of future fracture using Fracture Risk Assessment Tool (FRAX) were compared. RESULTS: The mean age at fracture site was significantly different among the 3 groups, groups W (66.57±10.03), S (73.50±9.07), and H (78.50±7.72). The most common site of OF were in the order of wrist, spine, and hip with the increase of age. The FRAX scores significantly increased (P<0.001) in the order of W (8.35±5.67), S (10.74±6.99), and H (13.88±7.98) in total patient, and same in primary fracture group (W, 7.50±4.18; S, 9.76±5.91; H, 11.93±6.61; P<0.001). The main site of prior fractures in secondary fracture was same lesion, which means that the prior fracture of secondary wrist fracture was wrist fracture such as spine for spine, hip for hip. CONCLUSIONS: We determined that as age increasing, the major sites of OF were different and FRAX scores increased. The most common site for secondary fracture was the same one. Hence, the risk of subsequent fracture in same site should be noted after patient suffered OF.

Update on implementation of GHS in Korea and revision of Industrial Safety and Health Act in relation to GHS.

To implement the globally harmonized system of classification and labelling of chemicals (GHS) in Korea, an inter-ministerial GHS committee, involving 8 ministries and an expert working group composed of 9 experts from relevant organizations and one private consultant, have made some progress towards implementation by 2008. As such, the first revision of the official Korean translated version of the GHS in accordance with the GHS purple book revision 1 in 2005, including annexes, started in August, 2006, was completed in December, 2006. The Ministry of Labor also finally revised the Industrial Safety and Health Act (ISHA) relating to the GHS and the detailed notification was announced on Dec 12, 2006 and became effective immediately. The revised ISHA will allow continued use of the existing hazard communication system until Jun 30, 2008. Other revisions of chemical-related regulations will follow soon to facilitate the implementation of the GHS by 2008. Besides, inter-ministerial collaborative efforts on harmonizing regulations and disseminating the GHS in Korea will continue to avoid any confusion or duplication and for the effective use of resources.