Purpose: To describe the incidence and mortality of upper tract urothelial carcinoma (UTUC) from 2002–2020 using data from the Korean National Health Insurance Service, which contains data from the entire Korean population. Materials and Methods: Reimbursement records for 43,255 patients diagnosed with primary UTUC (according to the International Classification of Disease 10th revision code C65 and C66) between 2002–2020 were retrieved. The study period was split into four: period I (2002–2005), period II (2006–2010), period III (2011–2015), and period IV (2016–2020). Trends were quantified by calculating the annual percentage change (APC). Mortality data were obtained from the Statistics Korea. Results: From 2002–2020, the incidence of UTUC in Korea increased gradually from 9.34 to 11.40 per 100,000 person-years. Although there was a male predominance, the male to female ratio did not change significantly over time; however, age at the time of diagnosis, the comorbidity index, and the proportion of patients undergoing open/laparoscopic surgery increased significantly over time. There was a modest improvement in 5-year survival (both all cause- and cancer-specific) over the study period. Multivariate analysis identified age at diagnosis, sex, the comorbidity index, and open/laparoscopic surgery as being associated with survival. Conclusions Between 2002 and 2020, the incidence of UTUC in Korea showed a general upward trend; however, survival outcomes have improved. These representative datasets from the Korean population might provide crucial information that enables clinicians to better understand of the epidemiology of UTUC in Korea.

Purpose: To report two instances of retinal arterial occlusive vasculitis following intravitreal injection of brolucizumab.Case summary: Two patients noted decreased visual acuity approximately one month after receiving intravitreal brolucizumab injections to treat wet age-related macular degeneration. In case 1, an 85-year-old male reported a reduction in visual acuity in his left eye, declining from a Snellen measurement of 0.2 to hand motion. In case 2, a 70-year-old female experienced a decline in visual acuity in her right eye from 0.4 to finger count at 50 cm. Both patients presented with anterior chamber reactions, and fluorescein angiography demonstrated delayed retinal artery filling time, leading to the diagnosis of retinal occlusive vasculitis. They were treated with both topical and systemic corticosteroids. For case 1, a subsequent vitrectomy was performed to remove the inflammatory membrane located behind the intraocular lens. However, despite aggressive interventions, neither patient showed visual improvement. Conclusions Retinal occlusive vasculitis, which can result from intraocular inflammation, may occur after intravitreal brolucizumab injection. This condition can lead to significant visual impairment even with aggressive treatment.

Background: Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator- activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined. Methods: This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months. Conclusion This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D.

BACKGROUND: Interstitial cystitis (IC) is a chronic and intractable disease that can severely deteriorate patients’ quality of life. Recently, stem cell therapy has been introduced as a promising alternative treatment for IC in animal models. We aimed to verify the efficacy and safety of the human perirenal adipose tissue-derived stromal vascular fraction (SVF) in an IC rat model. METHODS: From eight-week-old female rats, an IC rat model was established by subcutaneous injection of 200 lg of uroplakin3A. The SVF was injected into the bladder submucosal layer of IC rats, and pain scale analysis, awakening cytometry, and histological and gene analyses of the bladder were performed. For the in vivo safety analysis, genomic DNA purification and histological analysis were also performed to check tumorigenicity and thrombus formation. RESULTS: The mean pain scores in the SVF 20 ll group were significantly lower on days 7 and 14 than those in the control group, and bladder intercontraction intervals were significantly improved in the SVF groups in a dose-dependent manner. Regeneration of the bladder epithelium, basement membrane, and lamina propria was observed in the SVF group.In the SVF groups, however, bladder fibrosis and the expression of inflammatory markers were not significantly improved compared to those in the control group. CONCLUSION This study demonstrated that a perirenal adipose tissue-derived SVF is a promising alternative for the management of IC in terms of improving bladder pain and overactivity.

BACKGROUND: Immunoglobulin A (IgA) nephropathy (IgAN) is one of an important cause of progressive kidney disease and occurs when IgA settles in the kidney resulted in disrupts kidney’s ability to filter waste and excess water.Hydrogels are promising material for medical applications owing to their excellent adaptability and filling ability. Herein, we proposed a hyaluronic acid/gelatin (CHO-HA/Gel-NH2 ) bioactive hydrogel as a cell carrier for therapeutic kidney regeneration in IgAN. METHODS: CHO-HA/Gel-NH2 hydrogel was fabricated by Schiff-base reaction without any additional crosslinking agents. The hydrogel concentrations and ratios were evaluated to enhance adequate mechanical properties and biocompatibility for further in vivo study. High serum IgA ddY mice kidneys were treated with human urine-derived renal progenitor cells encapsulated in the hydrogel to investigate the improvement of IgA nephropathy and kidney regeneration. RESULTS: The stiffness of the hydrogel was significantly enhanced and could be modulated by altering the concentrations and ratios of hydrogel. CHO-HA/Gel-NH2 at a ratio of 3/7 provided a promising milieu for cells viability and cells proliferation. From week four onwards, there was a significant reduction in blood urea nitrogen and serum creatinine level in Cell/Gel group, as well as well-organized glomeruli and tubules. Moreover, the expression of pro-inflammatory and profibrotic molecules significantly decreased in the Gel/Cell group, whereas anti-inflammatory gene expression was elevated compared to the Cell group. CONCLUSION Based on in vivo studies, the renal regenerative ability of the progenitor cells could be further increased by this hydrogel system.

BACKGROUND: Immunoglobulin A (IgA) nephropathy (IgAN) is one of an important cause of progressive kidney disease and occurs when IgA settles in the kidney resulted in disrupts kidney’s ability to filter waste and excess water.Hydrogels are promising material for medical applications owing to their excellent adaptability and filling ability. Herein, we proposed a hyaluronic acid/gelatin (CHO-HA/Gel-NH2 ) bioactive hydrogel as a cell carrier for therapeutic kidney regeneration in IgAN. METHODS: CHO-HA/Gel-NH2 hydrogel was fabricated by Schiff-base reaction without any additional crosslinking agents. The hydrogel concentrations and ratios were evaluated to enhance adequate mechanical properties and biocompatibility for further in vivo study. High serum IgA ddY mice kidneys were treated with human urine-derived renal progenitor cells encapsulated in the hydrogel to investigate the improvement of IgA nephropathy and kidney regeneration. RESULTS: The stiffness of the hydrogel was significantly enhanced and could be modulated by altering the concentrations and ratios of hydrogel. CHO-HA/Gel-NH2 at a ratio of 3/7 provided a promising milieu for cells viability and cells proliferation. From week four onwards, there was a significant reduction in blood urea nitrogen and serum creatinine level in Cell/Gel group, as well as well-organized glomeruli and tubules. Moreover, the expression of pro-inflammatory and profibrotic molecules significantly decreased in the Gel/Cell group, whereas anti-inflammatory gene expression was elevated compared to the Cell group. CONCLUSION Based on in vivo studies, the renal regenerative ability of the progenitor cells could be further increased by this hydrogel system.

Background: This phase 3 study evaluated the efficacy and safety of 6-month treatment with romosozumab in Korean postmenopausal women with osteoporosis. Methods: Sixty-seven postmenopausal women with osteoporosis (bone mineral density [BMD] T-scores ≤–2.5 at the lumbar spine, total hip, or femoral neck) were randomized (1:1) to receive monthly subcutaneous injections of romosozumab (210 mg; n=34) or placebo (n=33) for 6 months. Results: At month 6, the difference in the least square (LS) mean percent change from baseline in lumbar spine BMD (primary efficacy endpoint) between the romosozumab (9.5%) and placebo (–0.1%) groups was significant (9.6%; 95% confidence interval, 7.6 to 11.5; P<0.001). The difference in the LS mean percent change from baseline was also significant for total hip and femoral neck BMD (secondary efficacy endpoints). After treatment with romosozumab, the percent change from baseline in procollagen type 1 N-terminal propeptide transiently increased at months 1 and 3, while that in C-terminal telopeptide of type 1 collagen showed a sustained decrease. No events of cancer, hypocalcemia, injection site reaction, positively adjudicated atypical femoral fracture or osteonecrosis of the jaw, or positively adjudicated serious cardiovascular adverse events were observed. At month 9, 17.6% and 2.9% of patients in the romosozumab group developed binding and neutralizing antibodies, respectively. Conclusion Treatment with romosozumab for 6 months was well tolerated and significantly increased lumbar spine, total hip, and femoral neck BMD compared with placebo in Korean postmenopausal women with osteoporosis (ClinicalTrials.gov identifier NCT02791516).

Objectives: Osteoporosis medications are widely available in South Korea, and well reimbursed by the Government Health Insurance; however, some expensive drugs are not reimbursed. The prescription of anti-osteoporosis drugs (AODs) are increasing for the elderly and for postmenopausal women. We investigate the secular trends of AODs in South Korea. Methods: We used the Intercontinental Medical Statistics Health Sales Audit between January 1, 2006 and December 31, 2018. We analyzed the total sales costs and market share of AODs including bisphosphonates, selective estrogen receptor modulators (SERMs), parathyroid hormone (PTH), calcitonins, and denosumab using the number of days of therapy (DOT). Changes of prescription patterns including original versus generic drugs, vitamin D combination, and types of medical institutions were also analyzed. Results: Bisphosphonates were the most frequently used drug during the study period although its DOT declined from 92.5% in 2008 to 80.0% in 2018. SERMs were the second-most used medication, and has maintained around 13% since 2015. The proportion of calcitonins has decreased since 2011, mainly due to malignancy risk. In contrast, the DOT of PTH and denosumab increased to 0.8% and 4.7% in 2018, respectively. The use of generics, vitamin D combination, and intravenous bisphosphonates has been increasing throughout the study period. Conclusions Prescription patterns using DOT are changing probably due to the increase in older adult patients and severely osteoporotic patients. There are other issues including safety and the launching of new drugs.

Objectives: Osteoporosis medications are widely available in South Korea, and well reimbursed by the Government Health Insurance; however, some expensive drugs are not reimbursed. The prescription of anti-osteoporosis drugs (AODs) are increasing for the elderly and for postmenopausal women. We investigate the secular trends of AODs in South Korea. Methods: We used the Intercontinental Medical Statistics Health Sales Audit between January 1, 2006 and December 31, 2018. We analyzed the total sales costs and market share of AODs including bisphosphonates, selective estrogen receptor modulators (SERMs), parathyroid hormone (PTH), calcitonins, and denosumab using the number of days of therapy (DOT). Changes of prescription patterns including original versus generic drugs, vitamin D combination, and types of medical institutions were also analyzed. Results: Bisphosphonates were the most frequently used drug during the study period although its DOT declined from 92.5% in 2008 to 80.0% in 2018. SERMs were the second-most used medication, and has maintained around 13% since 2015. The proportion of calcitonins has decreased since 2011, mainly due to malignancy risk. In contrast, the DOT of PTH and denosumab increased to 0.8% and 4.7% in 2018, respectively. The use of generics, vitamin D combination, and intravenous bisphosphonates has been increasing throughout the study period. Conclusions Prescription patterns using DOT are changing probably due to the increase in older adult patients and severely osteoporotic patients. There are other issues including safety and the launching of new drugs.

Background: Tissue engineering can be used for bladder augmentation. However, conventional scaffolds result in fibrosis and graft shrinkage. This study applied an alternative polycaprolactone (PCL)-based scaffold (diameter = 5 mm) with a noble gradient structure and growth factors (GFs) (epidermal growth factor, vascular endothelial growth factor, and basic fibroblast growth factor) to enhance bladder tissue regeneration in a rat model. Methods: Partially excised urinary bladders of 5-week-old male Slc:SD rats were reconstructed with the scaffold (scaffold group) or the scaffold combined with GFs (GF group) and compared with sham-operated (control group) and untreated rats (partial cystectomy group). Evaluations of bladder volume, histology, immunohistochemistry (IHC), and molecular markers were performed at 4, 8, and 12 weeks after operation. Results: The bladder volumes of the scaffold and GF group recovered to the normal range, and those of the GF group showed more enhanced augmentation. Histological evaluations revealed that the GF group showed more organized urothelial lining, dense extracellular matrix, frequent angiogenesis, and enhanced smooth muscle bundle regeneration than the scaffold group. IHC for α-smooth muscle actin, pan-cytokeratin, α-bungarotoxin, and CD8 revealed that the GF group showed high formation of smooth muscle, blood vessel, urothelium, neuromuscular junction and low immunogenicity. Concordantly, real-time polymerase chain reaction experiments revealed that the GF group showed a higher expression of transcripts associated with smooth muscle and urothelial differentiation. In a 6-month in vivo safety analysis, the GF group showed normal histology. Conclusion This study showed that a PCL scaffold with a gradient structure incorporating GFs improved bladder regeneration functionally and histologically.