Purpose: Hemophilia A is a genetic disorder characterized by a lack of factor VIII (FVIII). Emicizumab, a recombinant humanized bispecific monoclonal antibody, mimics the function of FVIII. In this article, we present data on an initial real-world evaluation of emicizumab use in Korean children with severe hemophilia A without inhibitors. Methods: This study was conducted from June 2020 to March 2024 at 4 centers in Korea. The participants were pediatric patients with severe hemophilia A without inhibitors who had received emicizumab treatment for over 6 months. The mean and median annualized bleeding rates (ABRs) and mean and median annual joint bleeding rates (AJBRs) were compared. Results: Each of the 21 patients in the study received an emicizumab loading regimen of 3 mg/kg weekly for 4 weeks, followed by a modified maintenance regimen of which 2 patients (9.5%) received a 1.5 mg/kg weekly dose, 3 patients (14.3%) received a 6 mg/kg dose every 4 weeks, and the remaining 16 patients (76.2%) received a 3 mg/kg dose every 2 weeks. Before emicizumab prophylaxis initiation, the mean and median ABRs for all patients were 7.04 (SD ± 5.83) and 6.52 (range 0–21.74), respectively. After receiving emicizumab treatment, the mean and mediam ABRs decreased to 0.41 and zero, respectively. Additionally, 85.7% of the patients achieved no bleeding events within 6 months of starting the treatment. Conclusion These first real-world data in Korea indicate that emicizumab is effective and safe for pediatric patients with severe hemophilia A without inhibitors.

Purpose: Hemophilia A is a genetic disorder characterized by a lack of factor VIII (FVIII). Emicizumab, a recombinant humanized bispecific monoclonal antibody, mimics the function of FVIII. In this article, we present data on an initial real-world evaluation of emicizumab use in Korean children with severe hemophilia A without inhibitors. Methods: This study was conducted from June 2020 to March 2024 at 4 centers in Korea. The participants were pediatric patients with severe hemophilia A without inhibitors who had received emicizumab treatment for over 6 months. The mean and median annualized bleeding rates (ABRs) and mean and median annual joint bleeding rates (AJBRs) were compared. Results: Each of the 21 patients in the study received an emicizumab loading regimen of 3 mg/kg weekly for 4 weeks, followed by a modified maintenance regimen of which 2 patients (9.5%) received a 1.5 mg/kg weekly dose, 3 patients (14.3%) received a 6 mg/kg dose every 4 weeks, and the remaining 16 patients (76.2%) received a 3 mg/kg dose every 2 weeks. Before emicizumab prophylaxis initiation, the mean and median ABRs for all patients were 7.04 (SD ± 5.83) and 6.52 (range 0–21.74), respectively. After receiving emicizumab treatment, the mean and mediam ABRs decreased to 0.41 and zero, respectively. Additionally, 85.7% of the patients achieved no bleeding events within 6 months of starting the treatment. Conclusion These first real-world data in Korea indicate that emicizumab is effective and safe for pediatric patients with severe hemophilia A without inhibitors.

Purpose: Hemophilia A is a genetic disorder characterized by a lack of factor VIII (FVIII). Emicizumab, a recombinant humanized bispecific monoclonal antibody, mimics the function of FVIII. In this article, we present data on an initial real-world evaluation of emicizumab use in Korean children with severe hemophilia A without inhibitors. Methods: This study was conducted from June 2020 to March 2024 at 4 centers in Korea. The participants were pediatric patients with severe hemophilia A without inhibitors who had received emicizumab treatment for over 6 months. The mean and median annualized bleeding rates (ABRs) and mean and median annual joint bleeding rates (AJBRs) were compared. Results: Each of the 21 patients in the study received an emicizumab loading regimen of 3 mg/kg weekly for 4 weeks, followed by a modified maintenance regimen of which 2 patients (9.5%) received a 1.5 mg/kg weekly dose, 3 patients (14.3%) received a 6 mg/kg dose every 4 weeks, and the remaining 16 patients (76.2%) received a 3 mg/kg dose every 2 weeks. Before emicizumab prophylaxis initiation, the mean and median ABRs for all patients were 7.04 (SD ± 5.83) and 6.52 (range 0–21.74), respectively. After receiving emicizumab treatment, the mean and mediam ABRs decreased to 0.41 and zero, respectively. Additionally, 85.7% of the patients achieved no bleeding events within 6 months of starting the treatment. Conclusion These first real-world data in Korea indicate that emicizumab is effective and safe for pediatric patients with severe hemophilia A without inhibitors.

Background: Recently developed imaging techniques, such as cone beam computed tomography (CBCT) and CAD/CAM technology, have facilitated reliable implant planning and implant surgical guide production by 3D printing. This study compared the accuracy of implant-guided surgery using the R2GATE® program with CBCT before and after surgery. Patients and methods: The study included patients who visited the Department of Oral and Maxillofacial Surgery at Chonnam National University Hospital from September 2021 to March 2022. Twenty-four implants were placed in eleven patients. Using R2GATE® Windows (Megagen implant, Daegu, Korea) software, implant placement was planned. The difference was measured by the CBCT before and after surgery. The cervical and apical distance and angular deviation of the implants were measured. Statistical analysis was performed using an independent t-test, Pearson correlation, and multiple regression analyses. Results: The three-dimensional linear distance difference between the planned implant and the placed implant was 0.97 ± 0.37 mm at the cervical and 1.13 ± 0.36 mm at the apical. The difference in angle deviation between the planned implant and the placed implant was 3.42 ± 2.12°. Among the variables affecting the accuracy of implant placement, a statistically significant difference was found when using a tissue-supported implant guide, implant diameter and implant length. Conclusion Based on these results, using the R2GATE® program is useful to use an implant digital surgical guide, and it will be used in various clinic.

BACKGROUND: Autophagy plays important roles in odontogenic differentiation of dental pulp cells (DPCs) in the developmental stage of tooth bud. Few studies have reported the role of autophagy during reparative dentin formation process. The objective of this study was to discover gene expression pattern correlated to autophagy and their role during odontogenic differentiation process in DPCs. METHODS: After tooth cavities were prepared on the mesial surface of lower first molar crown of rats. Odontogenic differentiation and reparative dentin formation were assessed based on detection of morphology change with hematoxylin and eosin staining. RESULTS: After tooth cavities were prepared on the mesial surface of lower first molar crown of rats, odontogenic differentiation and reparative dentin formation were assessed based on detection of morphology change with hematoxylin and eosin staining and dentin sialophosphoprotein (DSPP), whereas autophagy inhibitor 3-methyladenine (3MA) reversed. Results: of quantitative polymerized chain reaction array of autophagosome formation related genes revealed that GABARAPL2 was prominently upregulated while expression of other ATG8 family members were moderately increased after tooth cavity preparation. In addition, human DPCs incubated in differentiation medium predominantly upregulated MAP1LC3C, which selectively decreased by 3MA but not by autophagy enhancer trehalose. Knock-down of MAP1LC3C using shRNA resulted in strong downregulation of dentin matrix protein 1 and DSPP as well-known odontogenic marker compared to knock-down of MAP1LC3B during odontogenic differentiation process of human DPCs. CONCLUSION Our results suggest that MAP1LC3C plays a crucial role in odontogenic differentiation of human DPCs via regulating autophagic flux.

BACKGROUND: Autophagy plays important roles in odontogenic differentiation of dental pulp cells (DPCs) in the developmental stage of tooth bud. Few studies have reported the role of autophagy during reparative dentin formation process. The objective of this study was to discover gene expression pattern correlated to autophagy and their role during odontogenic differentiation process in DPCs. METHODS: After tooth cavities were prepared on the mesial surface of lower first molar crown of rats. Odontogenic differentiation and reparative dentin formation were assessed based on detection of morphology change with hematoxylin and eosin staining. RESULTS: After tooth cavities were prepared on the mesial surface of lower first molar crown of rats, odontogenic differentiation and reparative dentin formation were assessed based on detection of morphology change with hematoxylin and eosin staining and dentin sialophosphoprotein (DSPP), whereas autophagy inhibitor 3-methyladenine (3MA) reversed. Results: of quantitative polymerized chain reaction array of autophagosome formation related genes revealed that GABARAPL2 was prominently upregulated while expression of other ATG8 family members were moderately increased after tooth cavity preparation. In addition, human DPCs incubated in differentiation medium predominantly upregulated MAP1LC3C, which selectively decreased by 3MA but not by autophagy enhancer trehalose. Knock-down of MAP1LC3C using shRNA resulted in strong downregulation of dentin matrix protein 1 and DSPP as well-known odontogenic marker compared to knock-down of MAP1LC3B during odontogenic differentiation process of human DPCs. CONCLUSION Our results suggest that MAP1LC3C plays a crucial role in odontogenic differentiation of human DPCs via regulating autophagic flux.

Chronic obstructive pulmonary diseases (COPD) is an important disease featured as intense inflammation, protease imbalance, and air flow limitation and mainly induced by cigarette smoke (CS). In present study, we explored the effects of Pycnogenol® (PYC, pine bark extract) on pulmonary fibrosis caused by CS+lipopolysaccharide (LPS) exposure. Mice were treated with LPS intranasally on day 12 and 26, followed by CS exposure for 1 h/day (8 cigarettes per day) for 4 weeks. One hour before CS exposure, 10 and 20 mg/kg of PYC were administered by oral gavage for 4 weeks. PYC effectively reduced the number of inflammatory cells and proinflammatory mediators caused by CS+LPS exposure in bronchoalveolar lavage fluid. PYC inhibited the collagen deposition on lung tissue caused by CS+LPS exposure, as evidenced by Masson's trichrome stain. Furthermore, transforming growth factor-β1 (TGF-β1) expression and Smad family member 2/3 (Smad 2/3) phosphorylation were effectively suppressed by PYC treatment. PYC markedly reduced the collagen deposition caused by CS+LPS exposure, which was closely involved in TGF-β1/Smad 2/3 signaling, which is associated with pulmonary fibrotic change. These findings suggest that treatment with PYC could be a therapeutic strategy for controlling COPD progression.
Animals ; Bronchoalveolar Lavage Fluid ; Collagen ; Humans ; Inflammation ; Lung ; Lung Diseases, Obstructive ; Mice ; Phosphorylation ; Pulmonary Disease, Chronic Obstructive ; Pulmonary Fibrosis ; Smoke ; Tobacco Products*

Our previous proteomic study demonstrated that oxidative stress and antioxidant delphinidin regulated the cellular level of p27(kip1) (referred to as p27) as well as some heat shock proteins in human colon cancer HT 29 cells. Current study was conducted to validate and confirm the regulation of these proteins using both in vitro and in vivo systems. The level of p27 was decreased by hydrogen peroxide in a dose-dependent manner in human colon carcinoma HCT 116 (p53-positive) cells while it was increased upon exposure to hydrogen peroxide in HT 29 (p53-negative) cells. However, high concentration of hydrogen peroxide (100 micrometer) downregulated p27 in both cell lines, but delphindin, one of antioxidative anthocyanins, enhanced the level of p27 suppressed by 100 micrometer hydrogen peroxide. ICR mice were injected with varying concentrations of hydrogen peroxide, delphinidin and both. Western blot analysis for the mouse large intestinal tissue showed that the expression of p27 was upregulated by 25 mg/kg BW hydrogen peroxide. To investigate the association of p27 regulation with hypoxia-inducible factor 1-beta (HIF-1beta), the level of p27 was analyzed in wild-type mouse hepatoma hepa1c1c7 and Aryl Hydrocarbon Nuclear Translocator (arnt, HIF-1beta)-defective mutant BPRc1 cells in the absence and presence of hydrogen peroxide and delphinidin. While the level of p27 was responsive to hydrogen peroxide and delphinidin, it remained unchanged in BPRc1, suggesting that the regulation of p27 requires functional HIF-1beta. We also found that hydrogen peroxide and delphinidin affected PI3K/Akt/mTOR signaling pathway which is one of upstream regulators of HIFs. In conclusion, hydrogen peroxide and antioxidant delphinidin seem to regulate intracellular level of p27 through regulating HIF-1 level which is, in turn, governed by its upstream regulators comprising of PI3K/Akt/mTOR signaling pathway. The results should also encourage further study for the potential of p27 as a biomarker for intracellular oxidative or antioxidant status.
Animals ; Anthocyanins ; Aryl Hydrocarbon Receptor Nuclear Translocator ; Blotting, Western ; Carcinoma, Hepatocellular ; Cell Line ; Colon ; Colonic Neoplasms ; Heat-Shock Proteins ; HT29 Cells ; Humans ; Hydrogen Peroxide ; Mice ; Mice, Inbred ICR ; Oxidative Stress ; Proteins

In partial thickness burn injuries, silver sulfadiazine cream 1%(SSD, Silvadene(R)) is the most commonly used topical agent worldwide. But silver sulfadiazine cream 1% has no exudate absorption property. Usually after escar is removed from wound surface, Silvadene(R) is changed to saline wet gauze dressing to promote epithelization. Aquacel(R)(ConvaTec, UK) is a 100% sodium carboxymethylcellulose Hydrofiber material. It absorbs exudates directly into the hydrofibers by vertical wicking which allows rapid uptake of liquid into the fibers. The absorbed exudate fluid can be distributed to the entire dressing rather than just over the wound surface, which results in larger fluid absorption capacity. From April, 2003 to July, 2004 a study was done with 40 patients who had variable partial thickness burns. Aquacel(R) dressing was compared in 21 cases to silver sulfadiazine cream 1% and saline wet gauze dressings in 19 cases. In the Aquacel(R) cases, the average healing time on the face was 5.36+/-1.69 a day; on the hands was 8.46+/-2.15 a day; and, on the neck was 6.0+/-2.0 a day. With the Silvadene(R) and Saline wet gauze dressing, the average healing time on the face was 6.44+/-1.74 a day; on the hands was 13.79+/-5.35 a day; and, on the neck was 11.17+/-3.31 a day. As a result, the Aquacel(R) group showed a shorter healing time compared to the Silvadene(R) and saline wet gauze dressing group and patients were satisfied because of less pain and improved comfort. In conclusion, Aquacel(R) is a better choice for partial thickness burn injuries because of shorter healing time, less pain and more confortable dressing.
Absorption ; Bandages* ; Burns* ; Capillary Action ; Carboxymethylcellulose Sodium ; Exudates and Transudates ; Hand ; Humans ; Neck ; Silver Sulfadiazine ; Wounds and Injuries

Eosinophilic gastroenteritis is a rare disorder of unknown origin that is pathologically characterized by marked infiltration of eosinophils in the wall of the gastrointestinal tracts. Eosinophilic gastroenteritis is often classified according to the layer of the bowel wall involved. We experienced two cases of eosinophilic gastroenteritis. One case having whole small bowel wall involvement resulting in small bowel obstruction and eosinophilic ascites underwent bowel resection followed by oral steroid treatment. The other case having mucosal layer involvement with chronic diarrhea and hypoalbuminemia was treated with oral corticosteroid and responded dramatically. In addition, we report one case of hypereosinophilic syndrome involving the gastrointestinal tracts. The patient presented with abdominal pain, ascites, and urticaria. and also showed good response to oral steroid.
Abdominal Pain ; Ascites ; Diarrhea ; Eosinophils* ; Gastroenteritis* ; Gastrointestinal Tract ; Humans ; Hypereosinophilic Syndrome* ; Hypoalbuminemia ; Urticaria