Whole-Exome Sequencing in Papillary Microcarcinoma: Potential Early Biomarkers of Lateral Lymph Node Metastasis

Background@#Early identification of patients with high-risk papillary thyroid microcarcinoma (PTMC) that is likely to progress has become a critical challenge. We aimed to identify somatic mutations associated with lateral neck lymph node (LN) metastasis (N1b) in patients with PTMC. @*Methods@#Whole-exome sequencing (WES) of 14 PTMCs with no LN metastasis (N0) and 13 N1b PTMCs was performed using primary tumors and matched normal thyroid tissues. @*Results@#The mutational burden was comparable in N0 and N1b tumors, as the median number of mutations was 23 (range, 12 to 46) in N0 and 24 (range, 12 to 50) in N1b PTMC (P=0.918). The most frequent mutations were detected in PGS1, SLC4A8, DAAM2, and HELZ in N1b PTMCs alone, and the K158Q mutation in PGS1 (four patients, Fisher’s exact test P=0.041) was significantly enriched in N1b PTMCs. Based on pathway analysis, somatic mutations belonging to the receptor tyrosine kinase-RAS and NOTCH pathways were most frequently affected in N1b PTMCs. We identified four mutations that are predicted to be pathogenic in four genes based on Clinvar and Combined Annotation-Dependent Depletion score: BRAF, USH2A, CFTR, and PHIP. A missense mutation in CFTR and a nonsense mutation in PHIP were detected in N1b PTMCs only, although in one case each. BRAF mutation was detected in both N0 and N1b PTMCs. @*Conclusion@#This first comprehensive WES analysis of the mutational landscape of N0 and N1b PTMCs identified pathogenic genes that affect biological functions associated with the aggressive phenotype of PTMC.

Efficacy and Safety of Treatment with Quadruple Oral Hypoglycemic Agents in Uncontrolled Type 2 Diabetes Mellitus: A Multi-Center, Retrospective, Observational Study

BackgroundOnly few studies have shown the efficacy and safety of glucose-control strategies using the quadruple drug combination. Therefore, the aim of the present study was to investigate the usefulness of the quadruple combination therapy with oral hypoglycemic agents (OHAs) in patients with uncontrolled type 2 diabetes mellitus (T2DM).MethodsFrom March 2014 to December 2018, data of patients with T2DM, who were treated with quadruple hypoglycemic medications for over 12 months in 11 hospitals in South Korea, were reviewed retrospectively. We compared glycosylated hemoglobin (HbA1c) levels before and 12 months after quadruple treatment with OHAs. The safety, maintenance rate, and therapeutic patterns after failure of the quadruple therapy were also evaluated.ResultsIn total, 357 patients were enrolled for quadruple OHA therapy, and the baseline HbA1c level was 9.0%±1.3% (74.9±14.1 mmol/mol). After 12 months, 270 patients (75.6%) adhered to the quadruple therapy and HbA1c was significantly reduced from 8.9%±1.2% to 7.8%±1.3% (mean change, −1.1%±1.2%; PPConclusionThis study shows the therapeutic efficacy of the quadruple OHA regimen T2DM and demonstrates that it can be an option for the management of T2DM patients who cannot use insulin or reject injectable therapy.

Efficacy and Safety of Treatment with Quadruple Oral Hypoglycemic Agents in Uncontrolled Type 2 Diabetes Mellitus: A Multi-Center, Retrospective, Observational Study

BackgroundOnly few studies have shown the efficacy and safety of glucose-control strategies using the quadruple drug combination. Therefore, the aim of the present study was to investigate the usefulness of the quadruple combination therapy with oral hypoglycemic agents (OHAs) in patients with uncontrolled type 2 diabetes mellitus (T2DM).MethodsFrom March 2014 to December 2018, data of patients with T2DM, who were treated with quadruple hypoglycemic medications for over 12 months in 11 hospitals in South Korea, were reviewed retrospectively. We compared glycosylated hemoglobin (HbA1c) levels before and 12 months after quadruple treatment with OHAs. The safety, maintenance rate, and therapeutic patterns after failure of the quadruple therapy were also evaluated.ResultsIn total, 357 patients were enrolled for quadruple OHA therapy, and the baseline HbA1c level was 9.0%±1.3% (74.9±14.1 mmol/mol). After 12 months, 270 patients (75.6%) adhered to the quadruple therapy and HbA1c was significantly reduced from 8.9%±1.2% to 7.8%±1.3% (mean change, −1.1%±1.2%; PPConclusionThis study shows the therapeutic efficacy of the quadruple OHA regimen T2DM and demonstrates that it can be an option for the management of T2DM patients who cannot use insulin or reject injectable therapy.

Efficacy and Safety of Treatment with Quadruple Oral Hypoglycemic Agents in Uncontrolled Type 2 Diabetes Mellitus: A Multi-Center, Retrospective, Observational Study

Background@#Only few studies have shown the efficacy and safety of glucose-control strategies using the quadruple drug combination. Therefore, the aim of the present study was to investigate the usefulness of the quadruple combination therapy with oral hypoglycemic agents (OHAs) in patients with uncontrolled type 2 diabetes mellitus (T2DM). @*Methods@#From March 2014 to December 2018, data of patients with T2DM, who were treated with quadruple hypoglycemic medications for over 12 months in 11 hospitals in South Korea, were reviewed retrospectively. We compared glycosylated hemoglobin (HbA1c) levels before and 12 months after quadruple treatment with OHAs. The safety, maintenance rate, and therapeutic patterns after failure of the quadruple therapy were also evaluated. @*Results@#In total, 357 patients were enrolled for quadruple OHA therapy, and the baseline HbA1c level was 9.0%±1.3% (74.9± 14.1 mmol/mol). After 12 months, 270 patients (75.6%) adhered to the quadruple therapy and HbA1c was significantly reduced from 8.9%±1.2% to 7.8%±1.3% (mean change, –1.1%±1.2%; P<0.001). The number of patients with HbA1c <7% increased significantly from 5 to 68 (P<0.005). In addition, lipid profiles and liver enzyme levels were also improved whereas no changes in body weight. There was no significant safety issue in patients treated with quadruple OHA therapy. @*Conclusion@#This study shows the therapeutic efficacy of the quadruple OHA regimen T2DM and demonstrates that it can be an option for the management of T2DM patients who cannot use insulin or reject injectable therapy.

Association between Serum Free Thyroxine and Anemia in Euthyroid Adults: A Nationwide Study

BACKGROUND: Studies on the relationship between thyroid function and anemia in the euthyroid range are scarce. We aimed to evaluate the association between anemia and serum free thyroxine (fT4) and thyrotropin (TSH) in euthyroid adults.METHODS: Data on 5,352 participants aged ≥19 years were obtained from the Korea National Health and Nutrition Examination Survey VI (2013 to 2015). Anemia was defined as hemoglobin (Hb) <13 and <12 g/dL for men and women, respectively.RESULTS: Overall, 6.1% of participants had anemia, and more women (9.9%) had anemia than men (2.8%, P<0.001). In multivariate analysis, serum fT4 levels, but not TSH, were positively associated with serum Hb levels in both sexes (P<0.001, each). Serum Hb levels linearly reduced across decreasing serum fT4 quartile groups in both sexes (P<0.001, each). After adjusting for potential confounding factors, participants with low-normal fT4 had 4.4 (P=0.003) and 2.8 times (P<0.001) higher risk for anemia than those with high-normal fT4 among men and women, respectively. When participants were divided into two groups at 50 years of age, in younger participants, men and women with the first quartile were at higher risk of anemia than men with the second quartile (odds ratio [OR], 3.3; P=0.029) and women with the forth quartile (OR, 3.2; P<0.001), respectively. This association was not observed in older participants.CONCLUSION: These results suggest that a low-normal level of serum fT4 was associated with a lower serum Hb level and a higher risk of anemia in euthyroid adults, especially in younger participants.

Clinical Study on Blowout Fractures of the Medial Orbital Wall Reconstructed by Bulla Ethmoidalis Osteomucosal Flap / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Various surgical approaches have been employed to treat fractures of the medial orbital wall. Among them, the transnasal endoscopic approach provides the chance to avoid external scars and to observe the fracture site clearly. These approaches mostly require the use of grafts or splints. Authors carried out a retrospective study on the blowout fractures repaired by bulla ethmoidalis osteomucosal flap (BOMF) and compared them with the groups that were treated with silastic sheet only and with Med-pore(R) registered to investigate the merits of BOMF with respect to results and complications. SUBJECTS AND METHOD: We reviewed 62 cases (64 sides) of medial wall fractures that were treated surgically. They were diagnosed with 3 mm facial CT scans and treated according to the authors' indications from February 1998 to March 2004 at Namgwang Hospital, Seonam University. The surgical treatment consisted of the reconstruction of the fractures and the repair of the remaining bone defects by graft and splint, and the type of graft was selected according to the size of the defect. For minor defects, silastic sheet was used alone, whereas major defects were repaired with BOMF or Med-pore(R) registered. All patients were evaluated regularly for at least six months postoperatively. RESULTS: There were no differences in the aspects of the final treatment results of diplopia and enopthalmos. But in the aspects of postoperative crust formation and granulation, the cases that were repaired with BOMF showed better results as well as the economic merits. In the BOMF cases, the average duration of silastic sheet stenting was 12.5 days and it could reduce the follow up period. CONCLUSION: BOMF demonstrated better results in the respects of duration of silastic sheet stenting, postope-rative crust formation, granulation and economic cost.

Mitochondrial DNA Copy Number in the Patients of Korean Polycystic Ovary Syndrome (PCOS) / 대한불임학회지

OBJECTIVE: We analyzed quantification of mitochondria DNA (mtDNA) to investigate the relationship of mitochondria and pathogenesis of PCOS. MATERIALS AND METHODS: Peripheral blood samples were collected from 28 patients with PCOS who were under the inclusion criteria for PCOS and from 28 healthy controls. Genomic DNA was used to analyze real-time PCR for mtDNA copy number quantification. The mtDNA copy number was compared between the control and PCOS groups. All data was expressed as mean +/- SD. Statistical analysis was assessed by t-test. RESULTS: In this study, the mtDNA CT was 11.67+/-0.422 in PCOS patients and 11.51+/-0.722 in control group, respectively. The mtDNA copy number was 1726410.71+/-407858.591 the patients of in PCOS and 2167887.51+/-252459.28 in control group (p=0.08), respectively. CONCLUSION: In our study, using real-time PCR, there was a tendency of lower mtDNA copy number in the patients of PCOS when comparing to the control group even though statistical difference was not significant. However, more extensive analysis is required to clarity relationship between mtDNA copy number and pathogenesis of PCOS.

The Distribution of I/D Polymorphism in the ACE Gene between Korean Young Controls and Athletes / 체질인류학회지

A number of genetic and environmental factors influence athletic performance. Cardiovascular fitness is an important factor of athletic success, and ACE gene is a good candidate for regulating cardiac and vascular function. Because younger subjects have less chance of being exposed to environmental factors than older ones, genetic factors have a relatively greater influence on younger subjects. The aim of this study was to investigate the distribution of I/D polymorphism in the ACE gene between Korean young controls and athletes. By association study, there were no significant differences in genotype and allele distributions between two groups, respectively (P> 0.05). When stratified by sporting disciplines, the significant difference in distribution was not also detected in our study (P> 0.05). These results do not support the hypothesis that the I/D polymorphism in the ACE gene is associated with endurance performance in Korean young subjects.

The Prevalence of Otitis Media in the Young Adult Men Group in Gwangju . Chonnam, Korea / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Otitis media is one of the most common inflammatory disorders in the field of otolaryngology. Fortunately, with development in antibiotics and advances in preventive therapy otitis media is on the decrease. Nevertheless, there are only few reports about the prevalence rate of otitis media in Korea. Therefore, we investigated the prevalence of each type of otitis media among young adults in Gwangju and the Province of Chonnam, Korea. SUBJECTS AND METHOD: 28, 200 men aged 19 years old who underwent physical examination for conscription at the Military Manpower Administration in Gwangju from February to september, 2002 were analyzed, retrospectively. RESULTS: The overall prevalence of otitis media was 0.219%. Prevalence of each subtype was as follows; acute otitis media, 0%; otitis media with effusion, 0.049%; chronic otitis media, 0.17%, respectively. In the group of chronic otitis media, chronic perforated otitis media was 95.8%. The prevalence of otitis media did not vary by urban-rural difference, nor by coastal-inland area. CONCLUSION: The prevalence rate of chronic otitis media was remarkably decreased, compared with 10 years ago (0.70%), and conspicuously with 20 years ago (2.81%). Therefore, we think this low prevalence rate is partially due to remarkable improvement in socioeconomic conditions with better nutrition, housing, hygienic condition, social environments and advances in public health and medical care.