Accelerated national lot release on COVID-19 vaccines in Republic of Korea.

Independent quality testing of samples from vaccine lots is part of quality assurance, especially to ensure the consistency of production lot by lot. Effective national lot release system that ensures the quality of each lot of vaccine before it is on the market is important because vaccines are intended to healthy people. In order to respond more quickly to public health crises such as the COVID-19 pandemic, the MFDS implements accelerated national lot release for rapid vaccination in Republic of Korea. For the accelerated system, improvement has been made in terms of timing of application for lot release and required documents. In addition, the processing period has been shortened and sampling method and test items have been streamlined. A thorough preparation for accelerated lot release has been developed by establishing test methods for a new platform in advance. As a result, a total of 43.88 million doses have been released within eight days on average. The accelerated lot release system has contributed significantly to rapid COVID-19 vaccination in Korea.

Simplified Free Gingival Graft Around Implants Using Medical Grade Tissue Cyanoacrylate: A Case Series Report.

The free gingival graft (FGG) procedure using suturing techniques has been widely utilized to effectively increase the amount of attached keratinized gingiva. However, conventional suturing procedures are time-consuming and technique-sensitive. Simplified FGG procedure around teeth and dental implants using medical grade tissue adhesive (cyanoacrylate) is known to overcome drawbacks of traditional suture techniques. However, the clinical application of cyanoacrylate as a means of stabilizing the graft has not been a common practice. The aim of this report demonstrates simplified FGG procedures around dental implants using cyanoacrylate with follow-up results.

A digital approach to fabricating an abutment replica to control cement volume in a cement-retained implant prosthesis.

If a cement-retained implant prosthesis is placed on an abutment, excess cement should be minimized or removed to prevent periimplant inflammation. Various methods for fabricating an abutment replica have been introduced to maintain tissue health and reduce clean-up time. The purpose of this article is to present an alternative technique for fabricating an abutment replica with computer-aided design/computer-aided manufacturing (CAD/CAM) technology.

Ligation of the left hepatic vein for dilated intrahepatic collaterals late after fontan operation.

A 17-year-old male presented with two episodes of syncope, cyanosis, and exercise intolerance 13 years after the Fontan operation. Echocardiography and magnetic resonance imaging showed dilated intrahepatic collaterals, which drained into the atrium through the left hepatic vein, and 24-hour Holter monitoring revealed sinus node dysfunction. We performed ligation of the left hepatic vein using intrahepatic collaterals as channels draining hepatic venous blood into the Fontan pathway, and implanted an epicardial dual chamber pacemaker. At one-year follow-up, the patient remained asymptomatic and his cardiac performance was much improved.

Flapless transcrestal sinus augmentation using hydrodynamic piezoelectric internal sinus elevation with autologous concentrated growth factors alone.

PURPOSE: The purpose of this retrospective study was to evaluate the success rate of implants and the amount of sinus augmentation using the flapless hydrodynamic piezoelectric internal sinus elevation (HPISE) technique with autologous concentrated growth factors (CGF) alone. MATERIALS AND METHODS: A total of 11 maxillary sinuses were augmented using the HPISE technique through the flapless transcrestal approach. Sixteen implants (average 11.38 mm in length and 4.83 mm in diameter), with 2 different surfaces, were placed simultaneously with CGF alone. Plain panoramic radiograms and cone-beam computed tomograms (CBCT) were taken in all patients to evaluate the sinus augmentation preoperatively and postoperatively. RESULTS: The sinus membranes were successfully elevated, averaging 13.95 ± 6.61 mm in immediate postoperative CBCT without any iatrogenic perforation. After an average 23.8 weeks, the average bone gain above the sinus floor was 8.23 ± 2.88 mm in the axial aspect of CBCT. No complications were recorded in any patients during the follow-up period. CONCLUSION: The flapless transcrestal approach to the sinus augmentation using the HPISE technique with autologous CGF alone could be an alternative to the lateral approach, even at severely resorbed edentulous posterior maxilla with insufficient bone height.

Benefit of the replaceable bony window in lateral maxillary sinus augmentation: clinical and histologic study.

PURPOSE: This retrospective study demonstrates, by clinical and histologic evaluation, the benefit of the replaceable bony window as a homologous bony barrier in lateral sinus augmentation. MATERIALS AND METHODS: A total of 103 maxillary sinus augmentations were performed using a piezoelectric device and a Er,Cr:YSGG laser apparatus. The detached bony windows were repositioned over various bone grafts. Sixteen bone biopsy specimens were harvested at the time of uncovering or implant placement. RESULTS: Three sinuses developed postoperative infections (2.91%). After 6 to 8 months of healing, uncovering procedures were carried out. Radiographically, reconstruction of the lateral sinus wall was observed in all cone-beam computed tomogram. Clinically, complete bone healing between the replaceable bony window and the lateral sinus wall was observed in all cases, except for the 3 infected sinuses (100 sinuses, 97.09%). Histologically, favorable new bone formation was observed in all specimens without any fibrous connective tissue invagination. More mature bone was observed along the floor of the replaceable bony window than at the center of the graft site. CONCLUSION: This study demonstrates that the replaceable bony window acts as an osteoinductive homologous barrier membrane over various bone graft materials and accelerates new bone formation in lateral sinus augmentation.

Comparative histomorphometric analysis of maxillary sinus augmentation with absorbable collagen membrane and osteoinductive replaceable bony window in rabbits.

PURPOSE: The aim of this animal study was to evaluate, through histomorphometric evaluation, bone regeneration in rabbit maxillary sinuses with absorbable collagen membranes and osteoinductive replaceable bony windows over bone grafts. MATERIALS AND METHODS: Bilateral sinus augmentation procedures were performed in 16 adult male rabbits. The rabbits were randomly assigned to 4 groups of 4 rabbits each. Rectangular replaceable bony windows were made with a piezoelectric thin saw insert. In control group, grafted ß-tricalcium phosphate (ß-TCP) was covered by absorbable collagen membranes. In experimental groups, ß-TCP was grafted and covered by replaceable bony windows. The rabbits were killed at 1, 2, 4, and 8 weeks postoperatively. The augmented sinuses were stained with hematoxylin-eosin and Masson trichrome stains and examined, under light microscopy, for newly formed bone and soft tissue changes in the maxillary sinuses. RESULTS: Histologically, significantly higher and faster new bone formation was observed in the augmented sinuses of the experimental groups, receiving homologous replaceable bony windows than in those of the control group receiving collagen membranes. CONCLUSION: This study demonstrates that, for augmentation, the use of the homologous replaceable bony window over bone graft material on the maxillary sinus accelerates bone regeneration.

Identification of KCNN2 as a susceptibility locus for coronary artery aneurysms in Kawasaki disease using genome-wide association analysis.

Kawasaki disease (KD) is often complicated by coronary artery lesions (CALs), including aneurysms. Because of the complications associated with KD, this disorder is the leading cause of acquired heart disease in children from developed countries. To identify genetic loci that confer a higher risk of developing CALs, we performed a case-control association study using previous genome-wide association study data for samples from KD cases only (n=186) by grouping KD patients without CALs (control: n=123) vs KD patients with extremely large aneurysms (diameter>5 mm) (case: n=17). Twelve loci with one or more sequence variants were found to be significantly associated with CALs (P<1 × 10(-5)). Of these, an SNP (rs17136627) in the potassium intermediate/small conductance calcium-activated channel, subfamily N, member 2 (KCNN2) at 5q22.3 was validated in 32 KD patients with large aneurysms (diameter>5 mm) and 191 KD patients without CALs (odds ratio (OR)=12.6, P(combined)=1.96 × 10(-8)). This result indicates that the KCNN2 gene can have an important role in the development of coronary artery aneurysms in KD.

Comparative Histomorphometric Analysis of Bone Regeneration According to Bone Graft Type.

PURPOSE: To use histomorphometric analysis to evaluate bone reconstruction in rabbit calvaria with autogenous bone, anorganic bovine bone, undecalcified human tooth bone (UdTB), and decalcified human tooth bone (dTB) grafts. MATERIALS AND METHODS: Extracted human teeth were crushed, and tooth bone with and without decalcification was prepared. Bony defects were made in 10 rabbit calvaria and allocated to one of the following four groups: group 1, in which UdTB was grafted; group 2, in which dTB was grafted; group 3, in which anorganic bovine bone was grafted; group 4, in which autogenous bone was grafted. The rabbits were sacrificed at 2 or 8 weeks postoperatively, and histomorphometric comparison was performed. RESULTS: Histologically, new bone formation was observed at the defect margin and around all graft materials. The dTB group revealed significantly greater new bone areas at 2 and 8 weeks compared to the UdTB group and the anorganic bovine bone group (P < .05). The dTB group revealed no significant difference in the new bone area at 2 weeks but revealed significantly less new bone area at 8 weeks compared to the autogenous bone group (P < .05). The dTB group also revealed significantly less graft material area compared to the anorganic bovine bone group at 8 weeks (P < .05). The autogenous bone group revealed significantly less graft material area and significantly greater bone marrow area compared to other groups at 8 weeks (P < .05). CONCLUSIONS: Grafting with dTB resulted in better bone regeneration than UdTB and anorganic bovine bone grafting at 8 weeks and addresses the potential disadvantages of autogenous bone grafting.

Assessment of risk factors for Korean children with Kawasaki disease.

Kawasaki disease (KD) is the most common cause of acquired heart disease in children. Intravenous immunoglobulin (IVIG) is the standard therapy for KD, but more than 10% of KD patients do not respond to IVIG and are at high risk for the development of coronary artery lesions (CALs). To identify clinical and genetic risk factors associated with CAL development and IVIG nonresponsiveness, this study analyzed the clinical data for 478 Korean KD patients. Multivariate logistic regression analysis showed that incomplete KD, IVIG nonresponse, fever duration of 7 days or longer, and the CC/AC genotypes of the rs7604693 single nucleotide polymorphism (SNP) in the PELI1 gene were significantly associated with the development of CALs, with odds ratios (ORs) ranging from 2.06 to 3.04. The risk of CAL formation was synergistically increased by the addition of individual risk factors, particularly the genetic variant in the PELI1 gene. Multivariate analysis also showed that a serum albumin level of 3.6 g/dl or lower was significantly associated with nonresponsiveness to IVIG [OR, 2.76; 95% confidence interval (CI), 1.34-5.68; P = 0.006]. Conclusively, incomplete KD, IVIG nonresponsiveness, long febrile days, and the rs7604693 genetic variant in the PELI1 gene are major risk factors for the development of CALs, whereas low serum albumin concentration is an independent risk factor for IVIG nonresponsiveness.

Variations in the number of CCL3L1 gene copies and Kawasaki disease in Korean children.

High-dose intravenous immunoglobulin (IVIG) therapy is the highly effective and standard treatment for Kawasaki disease (KD). However, ~20 % of KD patients have persistent fever or recurrence of fever after the initial IVIG treatment, which increases the risk for coronary artery lesions (CALs). Furthermore, the mechanism of IVIG resistance in KD patients still is unknown. The number of CC chemokine ligand 3-like 1 (CCL3L1) gene copies is reported to be associated with KD and IVIG resistance in Japanese patients. In addition, the authors observed significant upregulation of the CCL3L1 gene expression after in vitro immunoglobulin treatment in B cell lines derived from KD patients. Therefore, this study of 459 KD patients and 496 healthy control subjects tested whether the number of CCL3L1 gene copies is associated with a risk of KD, CALs, and/or IVIG resistance in Korean KD patients. However, the number of CCL3L1 gene copies was not associated with KD (P = 0.18), CAL formation (P = 0.062), or the IVIG resistance (P = 0.90). Therefore, the results indicate that the number of CCL3L1 gene copies does not have a role in susceptibility to KD or CALs nor with IVIG resistance in Korean KD patients.

Minimally invasive sinus augmentation using ultrasonic piezoelectric vibration and hydraulic pressure: a multicenter retrospective study.

PURPOSE: The purpose of this study was to evaluate the success rate of implants and vertical bone gain of edentulous posterior maxilla using ultrasonic piezoelectric vibration and hydraulic pressure, namely the hydrodynamic piezoelectric internal sinus elevation (HPISE) technique through a crestal approach. MATERIALS AND METHODS: A total of 250 maxillary sinuses were augmented using HPISE and 353 implants (averaging 11.8 mm in length and 4.5 mm in diameter), with 12 different systems, were placed simultaneously with or without additional bone grafting. Plain radiograms and cone beam computed tomograms were taken in all patients to evaluate sinus augmentation. RESULTS: Membrane perforation was recorded at 10 of the 353 implant sites. The perforation rate was 2.83%. The total success rate of implantation was 97.2% after an average of 69.3 weeks of loading. CONCLUSION: The crestally approached sinus augmentation using ultrasonic piezoelectric vibration and hydraulic pressure is an additional method of maxillary sinus augmentation.

A genome-wide association analysis reveals 1p31 and 2p13.3 as susceptibility loci for Kawasaki disease.

Kawasaki disease (KD) is an acute self-limited vasculitis of infants and children that manifests as fever and signs of mucocutaneous inflammation. Coronary artery aneurysms develop in approximately 15-25% of untreated children. Although the etiology of KD is largely unknown, epidemiologic data suggest the importance of genetic factors in the susceptibility to KD. In order to identify genetic variants that influence KD susceptibility, we performed a genome-wide association study (GWAS) using Affymetrix SNP array 6.0 in 186 Korean KD patients and 600 healthy controls; 18 and 26 genomic regions with one or more sequence variants were associated with KD and KD with coronary artery lesions (CALs), respectively (p < 1 × 10(-5)). Of these, one locus on chromosome 1p31 (rs527409) was replicated in 266 children with KD and 600 normal controls (odds ratio [OR] = 2.90, 95% confidence interval [CI] = 1.85-4.54, P (combined) = 1.46 × 10(-6)); and a PELI1 locus on chromosome 2p13.3 (rs7604693) was replicated in 86 KD patients with CALs and 600 controls (OR = 2.70, 95% CI = 1.77-4.12, P (combined) = 2.00 × 10(-6)). These results implicate a locus in the 1p31 region and the PELI1 gene locus in the 2p13.3 region as susceptibility loci for KD and CALs, respectively.

Perivascular brightness of coronary arteries in Kawasaki disease.

OBJECTIVE: Because perivascular echo brightness (PEB) of coronary arteries has been proposed as a criterion for diagnosis of incomplete Kawasaki disease, we assessed the clinical importance of PEB during the acute phase of disease. STUDY DESIGN: We enrolled 58 patients with Kawasaki disease who underwent two-dimensional strain analysis of images of pericoronary tissue taken during the acute and the convalescent phases. Echogenicity of pericoronary tissue and of the blood pool was determined by speckle tracking in the respective areas of imaging as the averages of integrated backscatter over a single cardiac cycle. PEB was defined as echogenicity of pericoronary tissue minus blood pool. RESULTS: PEB did not differ in the acute phase in patients and control subjects (P = .10) and between phases of disease (P = .25). In comparison between patient groups, the presence of pericardial effusion was higher in patients with higher PEB during the acute phase (n = 30) than in the remaining patients (33% versus 4%, P < .01). CONCLUSIONS: PEB did not differ between patients and control subjects and is only associated with the presence of pericardial effusion during the acute phase of Kawasaki disease. Our data do not confirm the reliability of PEB as a useful diagnostic sign of incomplete Kawasaki disease.

Molecular cytogenetic and clinical characterization of a patient with a 5.6-Mb deletion in 7p15 including HOXA cluster.

Here, we describe the clinical features of a boy with a 5.6-Mb deletion at chromosome 7p15.1-p15.3. He has mild facial anomalies, hand-foot abnormalities, hypospadias, congenital heart defects, and supernumerary nipples. This deletion was detected by array comparative genomic hybridization and verified by fluorescence in situ hybridization using BACs selected from the USCS genome browser. This deletion was not found in subsequent FISH analysis of the parental chromosomes. The deleted region contains several genes, including contiguous developmental genes on the HOXA cluster, which play a role in regulating aspects of morphogenesis during normal embryonic development. The patient's limb and urogenital features were similar to those observed in hand-foot-genital syndrome, which is caused by haploinsufficiency of HOXA13, whereas the congenital heart defect may reflect the deletion of HOXA3. We hypothesized that many clinical features of the patient were due to combined haploinsufficiency of the HOXA cluster. Our study also demonstrates the clinical usefulness of a molecular cytogenetic tool that is capable of detecting imbalances in the genome.

The outcome of open heart surgery for congenital heart disease in infants with low body weight less than 2500 g.

Although the outcome of neonatal cardiac surgery has dramatically improved, low body weight (LBW) is still considered an important risk for open heart surgery. The factors contributing to poor outcomes in LBW infants, however, are still unclear. We investigated risk factors for poor outcomes in infants weighing <2500 g who underwent surgical correction with cardiopulmonary bypass (CPB). From January 1995 to December 2009, 102 consecutive patients were included in this study. Median age and body weight at the time of surgery was 19 (range 1 to 365) days and 2.23 kg (range 1.3 to 2.5), respectively. Corrective surgery was performed on 75 infants. The median follow-up duration was 45.03 months (range 0.33 to 155.23). There were 23 (22.5%) hospital mortalities. Emergency surgery and low cardiac output (LCO) were associated with early mortality; however, body weight, Aristotle basic complex score, and type of surgery was not. Early morbidities, including delayed sterna closure, arrhythmia, and chylothorax, occurred in 39 (38.2%) infants. The overall actuarial survival rate at 10 years was 74.95% ± 4.37%. In conclusion, among infants weighing <2500 g who underwent open heart surgery with CPB, perioperative hemodynamic status, such as emergency surgery and LCO, strongly influenced early mortality. In contrast, LBW itself was not associated with patient morbidity or mortality.

Bone regeneration in the maxillary sinus using an autologous fibrin-rich block with concentrated growth factors alone.

PURPOSE: The purpose of this study was to evaluate the predictability of new bone formation in the maxillary sinus using an autologous fibrin-rich blocks with concentrated growth factors (CGFs) alone as an alternative to graft material. MATERIALS AND METHODS: A total of sixty-one sinus grafts were consecutively performed using the lateral window approach. After making replaceable bony window, the sinus membrane was elevated to make a new compartment. After 113 implants (average 13 mm high) with 11 different systems were placed simultaneously, the collected fibrin-rich blocks with CGFs alone were inserted in the sinus. To seal the lateral window, the bony window was repositioned. Radiographic, clinical, and histologic evaluation was performed to verify sinus augmentation. RESULTS: No significant postoperative complications developed. New bone consolidation in all augmented maxillary sinus was observed along the implants on plain radiographs and on cone-beam computed tomograms. The success rate of implant was 98.2% after an average of 10 months loading. CONCLUSION: Fibrin-rich blocks with CGFs act as an alternative to bone grafting and can be a predictable procedure for sinus augmentation.

Analyses of left ventricular myocardial deformation by speckle-tracking imaging during the acute phase of Kawasaki disease.

This study aimed to investigate left ventricular myocardial deformation in children with Kawasaki disease during the acute phase of their illness. A total of 50 patients and 35 normal control subjects were assessed. Data were obtained from the patients during the acute and convalescent phases of Kawasaki disease. Analyses of myocardial deformation [strain (epsilon), strain rate (SR)] was performed using two-dimensional speckle-tracking imaging in three directions (longitudinal, circumferential, and radial) at the basal and mid levels of the left ventricular myocardium. Basal longitudinal epsilon (P < 0.001) and midlongitudinal epsilon (P < 0.0001) were lower during the acute phase of the disease than in the control subjects and associated with serum albumin level and left ventricular mass index (LVMI). Midlongitudinal SR (P < 0.0001) was lower during the acute phase of Kawasaki disease than in the control subjects and associated with LVMI. Decreased systolic SR was not detected in any direction. In conclusion, left ventricular longitudinal systolic epsilon was significantly decreased during the acute phase of Kawasaki disease. This may be a result of myocardial swelling from myocarditis during the acute phase of the disease.

Malachite green induces cardiovascular defects in developing zebrafish (Danio rerio) embryos by blocking VEGFR-2 signaling.

Malachite green (MG) is a triphenyl methane dye used in various fields that demonstrates high toxicity to bacteria and mammalian cells. When bud stage zebrafish embryos were treated with MG at 125, 150, and 175ppb for 14h, the development of trunk including intersomitic vessels was inhibited in MG-treated flk-1-GFP transgenic embyos. MG clearly induced whole growth retardation. MG induced severe cell death in trunk intersomite region of zebrafish embryos and in human vascular endothelial cells in a dose-dependent manner. MG inhibited heart rates and cardiac looping. MG attenuated whole blood formation and inhibited vascular endothelial growth factor (VEGF)-induced receptor (R)-2 phosphorylation in vascular endothelial cells. In conclusion, MG significantly alters the cardiovascular development causing growth retardation in zebrafish through the blocking VEGFR-2 activation in early cardiovascular development. It suggests that MG may be an environmental toxic agent with the potential to induce embryonic cardiovascular defects in vertebrates.