1.In Vitro Investigation of HIF-1α as a Therapeutic Target for Thyroid-Associated Ophthalmopathy
Jeongmin LEE ; Jinsoo LEE ; Hansang BAEK ; Dong-Jun LIM ; Seong-Beom LEE ; Jung-Min LEE ; Sang-Ah JANG ; Moo Il KANG ; Suk-Woo YANG ; Min-Hee KIM
Endocrinology and Metabolism 2024;39(5):767-776
		                        		
		                        			 Background:
		                        			Thyroid-associated ophthalmopathy (TAO) involves tissue expansion and inflammation, potentially causing a hypoxic microenvironment. Hypoxia-inducible factor (HIF)-1α is crucial in fibrosis and adipogenesis, which are observed in TAO progression. We investigated the effects of hypoxia on orbital fibroblasts (OFs) in TAO, focusing on the role of HIF-1α in TAO progression. 
		                        		
		                        			Methods:
		                        			OFs were isolated from TAO and non-TAO patients (as controls). In addition to HIF-1α, adipogenic differentiation markers including peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer binding protein (CEBP) were measured by Western blot, and phenotype changes were evaluated by Oil Red O staining under both normoxia and hypoxia. To elucidate the effect of HIF-1α inhibition, protein expression changes after HIF-1α inhibitor treatment were evaluated under normoxia and hypoxia. 
		                        		
		                        			Results:
		                        			TAO OFs exhibited significantly higher HIF-1α expression than non-TAO OFs, and the difference was more distinct under hypoxia than under normoxia. Oil Red O staining showed that adipogenic differentiation of TAO OFs was prominent under hypoxia. Hypoxic conditions increased the expression of adipogenic markers, namely PPARγ and CEBP, as well as HIF-1α in TAO OFs. Interleukin 6 levels also increased in response to hypoxia. The effect of hypoxia on adipogenesis was reduced at the protein level after HIF-1α inhibitor treatment, and this inhibitory effect was sustained even with IGF-1 stimulation in addition to hypoxia. 
		                        		
		                        			Conclusion
		                        			Hypoxia induces tissue remodeling in TAO by stimulating adipogenesis through HIF-1α activation. These data could provide insights into new treatment strategies and the mechanisms of adipose tissue remodeling in TAO. 
		                        		
		                        		
		                        		
		                        	
2.Deep Vein Thrombosis Following Prolonged Prone Position Maintenance after Vitrectomy for Rhegmatogenous Retinal Detachment
Hansang LEE ; Chul Hee LEE ; Eun Young CHOI ; Junwon LEE ; Min KIM
Journal of the Korean Ophthalmological Society 2023;64(4):355-358
		                        		
		                        			 Purpose:
		                        			We report a rare case of deep vein thrombosis and pulmonary embolism that occurred following 2 weeks in the prone position after a trans pars plana vitrectomy with gas tamponade to treat rhegmatogenous retinal detachment.Case Summary: A 49-year-old man without a remarkable medical history visited our clinic complaining of gradual vision loss on the inferior side of the left eye. In fundus examinations, rhegmatogenous retinal detachment involving the macula with multiple tears was noted. After trans pars plana vitrectomy with gas tamponade, the patient was encouraged to maintain a prone position for retinal reattachment. However, after 2 weeks in the prone position, he complained of right calf pain and swelling. The department of cardiovascular surgery was consulted immediately and deep vein thrombosis and pulmonary embolism were diagnosed. After deep vein thrombectomy and anticoagulation therapy, the lower extremity symptoms improved and the patient was stable during follow-up with a well attached retina. 
		                        		
		                        			Conclusions
		                        			When prolonged prone positioning after retina surgery is necessary, careful monitoring for the possibility of deep vein thrombosis and pulmonary embolism is required, especially in high-risk patients. 
		                        		
		                        		
		                        		
		                        	
3.Surgical Treatment of a Large Choroidal Melanoma
Hansang LEE ; Seung Min LEE ; Su-Jin SHIN ; Eun Young CHOI ; Junwon LEE ; Min KIM
Journal of the Korean Ophthalmological Society 2023;64(5):445-450
		                        		
		                        			 Purpose:
		                        			We report successful eyeball-preserving management of a patient with a large choroidal melanoma. We combined partial lamellar sclerouvectomy (PLSU) with ruthenium (Ru)-106 plaque brachytherapy.Case summary: A 48-year-old woman with a history of asthma visited our clinic with a chief complaint of gradual loss of vision at the nasal side of her right eye (best-corrected visual acuity 0.6). Fundus examination revealed a mushroom-shaped, dark choroidal mass 17.1 mm (basal diameter) × 14.2 mm (apical height). There was no evidence of distant metastasis. To remove the tumor while preserving the eyeball, we combined PLSU and simultaneous Ru-106 plaque brachytherapy with the patient under hypotensive general anesthesia. At 6 weeks postoperatively, trans pars plana vitrectomy with silicone oil injection was performed to remove the vitreous hemorrhage and treat the retinal detachment. Intravitreal bevacizumab (Avastin, Genentech Inc., San Francisco, CA, USA) (0.05 mL, 1.25 mg) was injected every 2 months to prevent the development of radiation retinopathy. No residual tumor, recurrence, or distant metastasis was noted during follow-up of 2 years. The patient was stable with no ocular complications at her last visit (2 years postoperatively). 
		                        		
		                        			Conclusions
		                        			Contrary to what we expected and despite the surgical difficulties, PLSU combined with Ru-106 plaque brachytherapy is a useful eyeball-preserving strategy even when encountering a very large choroidal melanoma (diameter > 16 mm and apical height > 10 mm). Such a melanoma was previously believed to be treatable only via enucleation. 
		                        		
		                        		
		                        		
		                        	
4.Spinal Sagittal Imbalance is Associated with Vertebral Fracture without a Definite History of Falls: Cross-Sectional, Comparative Study of Cohort with and without a Distal Radius Fracture
Jeong Hyun LEE ; Hansang LEE ; Hyun Sik GONG
Journal of Bone Metabolism 2023;30(4):339-346
		                        		
		                        			 Background:
		                        			Treating osteoporosis in patients with a distal radius fracture (DRF) became paramount at the Fracture Liaison Service. Spinal sagittal imbalance emerged as a risk factor for subsequent fractures. Therefore, here we investigated the spinal profile of patients with DRF to investigate its association with a history of falls and prevalent vertebral fractures. 
		                        		
		                        			Methods:
		                        			We reviewed the cases of 162 women presenting with DRF and 162 age-matched women without fracture who underwent an osteoporosis evaluation including bone mineral density (BMD) and lateral spine imaging. We compared the incidence of prevalent vertebral fracture and sagittal vertical axis (SVA) to measure spinal sagittal imbalance. We also performed a regression analysis of the risks of prevalent vertebral fracture, such as age, body mass index (BMI), BMD, and SVA. 
		                        		
		                        			Results:
		                        			The SVA was significantly smaller (indicating more stable sagittal balance) in patients with a DRF versus controls (16 mm vs. 34 mm, respectively; p<0.001). The incidence of a prevalent vertebral fracture was similar between groups (12% vs. 15%, respectively; p=0.332). In both groups, the SVA was significantly greater in those with versus without a vertebral fracture. The vertebral fracture was significantly associated with age and SVA but not BMI or spinal BMD. 
		                        		
		                        			Conclusions
		                        			Spinal sagittal balance was superior in DRF patients, yet the frequency of prevalent vertebral fractures was similar. The identification of this unique spinal profile in patients with DRF may increase our understanding of osteoporotic fractures. 
		                        		
		                        		
		                        		
		                        	
5.Retrospective Analysis of the Efficacy and Safety of Omidenepag Isopropyl 0.002% Ophthalmic Solution in Korean Patients
Hansang LEE ; Sang Yeop LEE ; Hyoung Won BAE ; Chan Yun KIM ; Wungrak CHOI
Journal of the Korean Ophthalmological Society 2023;64(10):939-944
		                        		
		                        			 Purpose:
		                        			This study aimed to analyze the clinical efficacy and safety of omidenepag isopropyl (OMDI) 0.002% in Korean patients. 
		                        		
		                        			Methods:
		                        			A retrospective study was conducted involving 306 patients diagnosed with glaucoma or ocular hypertension, who were administered OMDI 0.002% from May 2021 to June 2022. The primary outcomes were the change in intraocular pressure (IOP) at months 1, 3, and 6 compared to the baseline IOP, and the reactions to the OMDI drug. 
		                        		
		                        			Results:
		                        			Out of 235 patients who met the study inclusion criteria, the mean IOP was 16.5 ± 3.4 mmHg at baseline, 14.5 ± 3.0 mmHg at month 1, 14.3 ± 2.7 mmHg at month 3, and 14.7 ± 3.1 mmHg at month 6. The mean IOP reduction at month 6 was -1.6 ± 2.8 mmHg (p < 0.001). On analyzing the IOP by types of glaucoma, the mean IOP change at the 6-month point showed statistically significant results in all types, including normal tension glaucoma, primary open-angle glaucoma, and ocular hypertension (p < 0.05). The frequency of side effects in all patients was 29.8%, with the most commonly reported adverse drug reaction being hyperemia in 18.7% of the total patients. There was one case (0.4%) of uveitis after OMDI administration, but no other systemic adverse drug reactions were reported. 
		                        		
		                        			Conclusions
		                        			Omidenepag isopropyl demonstrated a statistically significant IOP-lowering effect in Korean patients with various types of glaucoma. This suggests that OMDI could potentially serve as a first-line treatment for glaucoma. 
		                        		
		                        		
		                        		
		                        	
6.Heart Rate Variability in Postoperative Patients with Nonfunctioning Pituitary Adenoma
Jeonghoon HA ; Hansang BAEK ; Chaiho JEONG ; Minsoo YEO ; Seung-Hwan LEE ; Jae Hyoung CHO ; Ki-Hyun BAEK ; Moo Il KANG ; Dong-Jun LIM
Endocrinology and Metabolism 2021;36(3):678-687
		                        		
		                        			Background:
		                        			Decreased heart rate variability (HRV) has been reported to be associated with cardiac autonomic dysfunction. Hypopituitarism in nonfunctioning pituitary adenoma (NFPA) is often linked to increased cardiovascular mortality. We therefore hypothesized that postoperative NFPA patients with hormone deficiency have an elevated risk of HRV alterations indicating cardiac autonomic dysfunction. 
		                        		
		                        			Methods:
		                        			A total of 22 patients with NFPA were enrolled in the study. Between 3 and 6 months after surgery, a combined pituitary function test (CPFT) was performed, and HRV was measured. The period of sleep before the CPFT was deemed the most stable period, and the hypoglycemic period that occurred during the CPFT was defined as the most unstable period. Changes in HRV parameters in stable and unstable periods were observed and compared depending on the status of hormone deficiencies. 
		                        		
		                        			Results:
		                        			In patients with adrenocorticotropic hormone (ACTH) deficiency with other pituitary hormone deficiencies, the low frequency to high frequency ratio, which represents overall autonomic function and is increased in the disease state, was higher (P=0.005). Additionally, the standard deviation of the normal-to-normal interval, which decreases in the autonomic dysfunction state, was lower (P=0.030) during the hypoglycemic period. In panhypopituitarism, the low frequency to high frequency ratio during the hypoglycemic period was increased (P=0.007). 
		                        		
		                        			Conclusion
		                        			HRV analysis during CPFT enables estimation of cardiac autonomic dysfunction in patients with NFPA who develop ACTH deficiency with other pituitary hormone deficiencies or panhypopituitarism after surgery. These patients may require a preemptive assessment of cardiovascular risk.
		                        		
		                        		
		                        		
		                        	
7.Preliminary Results of Teleconsultations Temporarily Allowed during the COVID-19 Pandemic
Hansang KIM ; Hyejin LEE ; Choon-Seon PARK ; Soomin KIM ; Sang-A CHO ; Seung Mi YOO ; Jee-Ae KIM ; Jin Yong LEE
Yonsei Medical Journal 2021;62(9):850-857
		                        		
		                        			Purpose:
		                        			During the COVID-19 pandemic, Korea has temporarily expanded coverage of teleconsultation to ensure access to essential health services. As a preliminary study, we investigated service utilization patterns and the characteristics of doctors and patients involved in these temporary teleconsultation services. 
		                        		
		                        			Materials and Methods:
		                        			Using national health insurance claims data from February 23, 2020 to June 30, 2020 from the Health Insurance Review and Assessment Service, 228269875 cases were identified. Among them, 567390 cases that received teleconsultation services were included in our study. We performed descriptive analyses according to the types of healthcare institutions. 
		                        		
		                        			Results:
		                        			In total, 6193 healthcare institutions provided teleconsultation. Of these, 5466 (88.3%) were clinics. Physicians providing teleconsultations were most likely to be doctors of internal medicine (34.0%) or pediatricians (7.0%) and based in the Seoul Metropolitan area (30.4%). In terms of patients undergoing teleconsultation, the most common major disease categories treated were circulatory system diseases (I00–I99). In a detailed analysis, hypertensive diseases (I10–I15) were the most common diagnoses, with a total of 88726 cases (15.6%), followed by diabetes mellitus at 60298 cases (10.6%). The proportion of Medical Aid recipients receiving teleconsultations was higher (9.5%) than other socioeconomic groups. Among all participants, 356622 cases (84.6%) were from a return visit, and 108838 cases (19.2%) received teleconsultation services without being prescribed drugs. 
		                        		
		                        			Conclusion
		                        			Temporarily allowed teleconsultation services were provided mostly to the following patients: 1) those scheduled for revisitation, 2) those with chronic diseases, and 3) those living in pandemic hotspots.
		                        		
		                        		
		                        		
		                        	
8.Heart Rate Variability in Postoperative Patients with Nonfunctioning Pituitary Adenoma
Jeonghoon HA ; Hansang BAEK ; Chaiho JEONG ; Minsoo YEO ; Seung-Hwan LEE ; Jae Hyoung CHO ; Ki-Hyun BAEK ; Moo Il KANG ; Dong-Jun LIM
Endocrinology and Metabolism 2021;36(3):678-687
		                        		
		                        			Background:
		                        			Decreased heart rate variability (HRV) has been reported to be associated with cardiac autonomic dysfunction. Hypopituitarism in nonfunctioning pituitary adenoma (NFPA) is often linked to increased cardiovascular mortality. We therefore hypothesized that postoperative NFPA patients with hormone deficiency have an elevated risk of HRV alterations indicating cardiac autonomic dysfunction. 
		                        		
		                        			Methods:
		                        			A total of 22 patients with NFPA were enrolled in the study. Between 3 and 6 months after surgery, a combined pituitary function test (CPFT) was performed, and HRV was measured. The period of sleep before the CPFT was deemed the most stable period, and the hypoglycemic period that occurred during the CPFT was defined as the most unstable period. Changes in HRV parameters in stable and unstable periods were observed and compared depending on the status of hormone deficiencies. 
		                        		
		                        			Results:
		                        			In patients with adrenocorticotropic hormone (ACTH) deficiency with other pituitary hormone deficiencies, the low frequency to high frequency ratio, which represents overall autonomic function and is increased in the disease state, was higher (P=0.005). Additionally, the standard deviation of the normal-to-normal interval, which decreases in the autonomic dysfunction state, was lower (P=0.030) during the hypoglycemic period. In panhypopituitarism, the low frequency to high frequency ratio during the hypoglycemic period was increased (P=0.007). 
		                        		
		                        			Conclusion
		                        			HRV analysis during CPFT enables estimation of cardiac autonomic dysfunction in patients with NFPA who develop ACTH deficiency with other pituitary hormone deficiencies or panhypopituitarism after surgery. These patients may require a preemptive assessment of cardiovascular risk.
		                        		
		                        		
		                        		
		                        	
9.Preliminary Results of Teleconsultations Temporarily Allowed during the COVID-19 Pandemic
Hansang KIM ; Hyejin LEE ; Choon-Seon PARK ; Soomin KIM ; Sang-A CHO ; Seung Mi YOO ; Jee-Ae KIM ; Jin Yong LEE
Yonsei Medical Journal 2021;62(9):850-857
		                        		
		                        			Purpose:
		                        			During the COVID-19 pandemic, Korea has temporarily expanded coverage of teleconsultation to ensure access to essential health services. As a preliminary study, we investigated service utilization patterns and the characteristics of doctors and patients involved in these temporary teleconsultation services. 
		                        		
		                        			Materials and Methods:
		                        			Using national health insurance claims data from February 23, 2020 to June 30, 2020 from the Health Insurance Review and Assessment Service, 228269875 cases were identified. Among them, 567390 cases that received teleconsultation services were included in our study. We performed descriptive analyses according to the types of healthcare institutions. 
		                        		
		                        			Results:
		                        			In total, 6193 healthcare institutions provided teleconsultation. Of these, 5466 (88.3%) were clinics. Physicians providing teleconsultations were most likely to be doctors of internal medicine (34.0%) or pediatricians (7.0%) and based in the Seoul Metropolitan area (30.4%). In terms of patients undergoing teleconsultation, the most common major disease categories treated were circulatory system diseases (I00–I99). In a detailed analysis, hypertensive diseases (I10–I15) were the most common diagnoses, with a total of 88726 cases (15.6%), followed by diabetes mellitus at 60298 cases (10.6%). The proportion of Medical Aid recipients receiving teleconsultations was higher (9.5%) than other socioeconomic groups. Among all participants, 356622 cases (84.6%) were from a return visit, and 108838 cases (19.2%) received teleconsultation services without being prescribed drugs. 
		                        		
		                        			Conclusion
		                        			Temporarily allowed teleconsultation services were provided mostly to the following patients: 1) those scheduled for revisitation, 2) those with chronic diseases, and 3) those living in pandemic hotspots.
		                        		
		                        		
		                        		
		                        	
10.Clinical activity of fulvestrant in metastatic breast cancer previously treated with endocrine therapy and/or chemotherapy
Mi Hwa HEO ; Hee Kyung KIM ; Hansang LEE ; Ji Yeon KIM ; Jin Seok AHN ; Young Hyuck IM ; Yeon Hee PARK
The Korean Journal of Internal Medicine 2019;34(5):1100-1106
		                        		
		                        			 BACKGROUND/AIMS:
		                        			We conducted a retrospective analysis of the clinical activity of fulvestrant in postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC) previously treated with endocrine therapy and/or chemotherapy.
		                        		
		                        			METHODS:
		                        			We reviewed the medical records of all patients with MBC treated at Samsung Medical Center between January 2009 and August 2016. Patients received fulvestrant 250 mg intramuscularly every 28 days (from January 2009 to November 2010) or 500 mg intramuscularly every 28 days (from December 2010 to August 2016). Tumor responses were assessed every 8 weeks and at the end of treatment, as well as when disease progression was suspected.
		                        		
		                        			RESULTS:
		                        			A total of 84 patients were included in this study. A median of two previous endocrine treatments had been performed; 79% of the patients had received two or more endocrine treatments. Forty-five patients (54%) had been treated with chemotherapy for MBC before the fulvestrant treatment course. Visceral metastasis was found in 49 patients (58%). The estimated median progression-free survival and overall survival were 4.4 months (95% confidence interval [CI], 3.4 to 5.5) and 32.5 months (95% CI, 17.6 to 47.4), respectively. The disease control rate was 40.5% (95% CI, 30.5 to 51.5); partial response was observed in 16% of the patients and stable disease was observed in 25% of the patients. The most frequently reported adverse reactions were mild-to-moderate grade myalgia (10.5% of the patients), injection site pain (7%), and fatigue (7%). Fulvestrant was generally well tolerated.
		                        		
		                        			CONCLUSIONS
		                        			Fulvestrant showed encouraging clinical activity and favorable feasibility in postmenopausal women with MBC who had been treated with multiple endocrine therapies and/or cytotoxic chemotherapies. 
		                        		
		                        		
		                        		
		                        	
            
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