Purpose: Desmopressin, frequently prescribed for nocturia, is associated with an elevated risk of hyponatremia. This study examined the incidence and risk factors of hyponatremia in male patients with benign prostatic hyperplasia using nationwide Korean health data. Materials and Methods: From the National Health Insurance Service database, we analyzed data on desmopressin and hyponatremia in Korean adults with benign prostatic hyperplasia between 2011 and 2012. The patients were followed-up until December 2020. We tested the effects of desmopressin on hyponatremia risk using propensity score-matched Cox regression models and Kaplan–Meier survival analysis. Results: Among 33,533 patients, the incidence of hyponatremia was 6.0%, 4.5%, and 5.0% in the desmopressin, alpha-blocker, and combination therapy groups, respectively. After propensity score matching, desmopressin use was not significantly associated with an increased risk of hyponatremia (hazard ratio 1.273, 95% confidence interval 0.988–1.640; p=0.062). Significant predictors of hyponatremia included advanced age, chronic heart failure, peripheral vascular disease, and renal disease. Conclusions Desmopressin prescription following careful patient selection and regular monitoring does not significantly increase the risk of hyponatremia compared to other lower urinary tract symptom treatments. Therefore, it remains a viable and effective option for managing nocturia, particularly in patients with nocturnal polyuria. However, clinicians should implement routine monitoring protocols, including serum sodium checks, particularly in high-risk populations, to ensure the safe and effective use of desmopressin.

Purpose: We aimed to assess the clinical efficacy and safety of combining silodosin and solifenacin for overactive bladder (OAB) in females. Methods: A retrospective analysis of 586 females with OAB was conducted. Patients received either combination therapy (silodosin 8 mg + solifenacin 5 mg) or monotherapy (solifenacin 5 mg) for 12 weeks. Baseline and follow-up assessments included the overactive bladder symptom score (OABSS), International Prostate Symptom Score (IPSS), quality of life (QoL), maximum flow rate (Qmax), voided volume (VV), and postvoid residual urine volume (PVR). Results: Overall, 287 and 299 patients received combination therapy and monotherapy respectively. Both groups experienced significant improvements in OABSS and total IPSS after 12 weeks. The combination therapy group demonstrated a greater improvement in QoL compared to the monotherapy group (P=0.031). No significant differences were observed in Qmax or VV between the groups. However, the combination therapy group showed a significant reduction in PVR compared to the monotherapy group (P<0.001). Conclusions Combining silodosin with solifenacin significantly improved OAB symptoms and QoL in females. This combination therapy was particularly effective in reducing postvoid residual volume compared to solifenacin alone. These findings suggest that adding an alpha-blocker to antimuscarinic therapy can enhance OAB management and patient satisfaction.

Purpose: We aimed to assess the clinical efficacy and safety of combining silodosin and solifenacin for overactive bladder (OAB) in females. Methods: A retrospective analysis of 586 females with OAB was conducted. Patients received either combination therapy (silodosin 8 mg + solifenacin 5 mg) or monotherapy (solifenacin 5 mg) for 12 weeks. Baseline and follow-up assessments included the overactive bladder symptom score (OABSS), International Prostate Symptom Score (IPSS), quality of life (QoL), maximum flow rate (Qmax), voided volume (VV), and postvoid residual urine volume (PVR). Results: Overall, 287 and 299 patients received combination therapy and monotherapy respectively. Both groups experienced significant improvements in OABSS and total IPSS after 12 weeks. The combination therapy group demonstrated a greater improvement in QoL compared to the monotherapy group (P=0.031). No significant differences were observed in Qmax or VV between the groups. However, the combination therapy group showed a significant reduction in PVR compared to the monotherapy group (P<0.001). Conclusions Combining silodosin with solifenacin significantly improved OAB symptoms and QoL in females. This combination therapy was particularly effective in reducing postvoid residual volume compared to solifenacin alone. These findings suggest that adding an alpha-blocker to antimuscarinic therapy can enhance OAB management and patient satisfaction.

Purpose: We aimed to assess the clinical efficacy and safety of combining silodosin and solifenacin for overactive bladder (OAB) in females. Methods: A retrospective analysis of 586 females with OAB was conducted. Patients received either combination therapy (silodosin 8 mg + solifenacin 5 mg) or monotherapy (solifenacin 5 mg) for 12 weeks. Baseline and follow-up assessments included the overactive bladder symptom score (OABSS), International Prostate Symptom Score (IPSS), quality of life (QoL), maximum flow rate (Qmax), voided volume (VV), and postvoid residual urine volume (PVR). Results: Overall, 287 and 299 patients received combination therapy and monotherapy respectively. Both groups experienced significant improvements in OABSS and total IPSS after 12 weeks. The combination therapy group demonstrated a greater improvement in QoL compared to the monotherapy group (P=0.031). No significant differences were observed in Qmax or VV between the groups. However, the combination therapy group showed a significant reduction in PVR compared to the monotherapy group (P<0.001). Conclusions Combining silodosin with solifenacin significantly improved OAB symptoms and QoL in females. This combination therapy was particularly effective in reducing postvoid residual volume compared to solifenacin alone. These findings suggest that adding an alpha-blocker to antimuscarinic therapy can enhance OAB management and patient satisfaction.

OBJECTIVES: The escalating burden of cardiovascular disease (CVD) is a critical public health issue worldwide. CVD, especially acute myocardial infarction (AMI) and stroke, is the leading contributor to morbidity and mortality in Korea. We aimed to develop algorithms for identifying AMI and stroke events from the National Health Insurance Service (NHIS) database and validate these algorithms through medical record review. METHODS: We first established a concept and definition of “hospitalization episode,” taking into account the unique features of health claims-based NHIS database. We then developed first and recurrent event identification algorithms, separately for AMI and stroke, to determine whether each hospitalization episode represents a true incident case of AMI or stroke. Finally, we assessed our algorithms’ accuracy by calculating their positive predictive values (PPVs) based on medical records of algorithm- identified events. RESULTS: We developed identification algorithms for both AMI and stroke. To validate them, we conducted retrospective review of medical records for 3,140 algorithm-identified events (1,399 AMI and 1,741 stroke events) across 24 hospitals throughout Korea. The overall PPVs for the first and recurrent AMI events were around 92% and 78%, respectively, while those for the first and recurrent stroke events were around 88% and 81%, respectively. CONCLUSIONS We successfully developed algorithms for identifying AMI and stroke events. The algorithms demonstrated high accuracy, with PPVs of approximately 90% for first events and 80% for recurrent events. These findings indicate that our algorithms hold promise as an instrumental tool for the consistent and reliable production of national CVD statistics in Korea.

Background: While polystyrene microplastics (PS-MPs) are emerging as potentially significant health threats, linked to cancer and reproductive dysfunction, their precise effects on human health remain largely unknown. We aimed to investigate the underlying mechanisms promoting microplastic-induced damage in the reproductive system. Methods: Thirty C57BL/6 male mice were randomly allocated into six equal-sized groups.Mice were exposed to fluorescent PS-MPs (5 µm, < 18%, green) at a dose of 1 and 3 mg/dL via oral gavage for 28 and 56 days, respectively (control, 0 mg/dL). The presence of antibodies and inflammatory and oxidative stress markers were evaluated using western blotting. Sperm analysis was also performed. Mouse testis Sertoli TM4 cells were divided into two groups:control (medium only) and PS-MPs (medium containing, 1,000 μg/mL) groups and cultured in vitro for 1, 24, 48, or 72 hours. The cells were cultured in a Ham’s F12: Dulbecco's Modified Eagle Medium medium with 0.25% fetal bovine serum at 37°C with humidified atmosphere of 5% carbon dioxide in the air. Protein analyses for interleukin (IL)-6, IL-10, NADPH-oxidase (NOX)-2, NOX-4, hypoxia-inducible transcription factor (HIF)-2α, monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-β were performed using western blotting. Results: The testes were evaluated after 28 and 56 days of exposure. Varying sizes of PS-MPs were detected in the testes (ranging from 5.870 to 7.768 µm). Significant differences in sperm concentration, motility, and the proportion of normal sperm were observed between the two groups. An increase in TGF-β, HIF-2α, and NOX-4 levels was observed using western blot analysis. However, no dose-dependent correlations were observed between the two groups.In vitro evaluation of the PS-MPs group displayed PS-MP penetration of the lumen of Sertoli cells after 1 hour. Further PS-MP aggregation within Sertoli cells was observed at 24, 48, and 72 hours. A significant increase in inflammatory protein expressions (IL-10, TGF-β, MCP-1, IL-6, TNF-α, and HIF-2α) was observed through western blotting, although oxidative agents did not show a significant increase. Conclusion PS-MPs induced reproductive dysfunction in male mice provide new insights into PS-MPs-associated toxicity in mammals.

Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) is a multipotent protein that plays essential roles in cellular responses to oxidative stress. Methods: To examine the role of APE1/Ref-1 in ischemia-reperfusion (I/R) injuries and hydrogen peroxide (H2O2)-induced renal tubular apoptosis, we studied male C57BL6 mice and human proximal tubular epithelial (HK-2) cells treated with H2O2 at different concentrations. The colocalization of APE1/Ref-1 in the proximal tubule, distal tubule, thick ascending limb, and collecting duct was observed with confocal microscopy. The overexpression of APE1/Ref-1 with knockdown cell lines using an APE1/Ref-1–specific DNA or small interfering RNA (siRNA) was used for the apoptosis assay. The promotor activity of nuclear factor kappa B (NF-κB) was assessed and electrophoretic mobility shift assay was conducted. Results: APE1/Ref-1 was predominantly localized to the renal tubule nucleus. In renal I/R injuries, the levels of APE1/Ref-1 protein were increased compared with those in kidneys subjected to sham operations. The overexpression of APE1/Ref-1 in HK-2 cells enhanced the Bax/Bcl-2 ratio as a marker of apoptosis. Conversely, the suppression of APE1/Ref-1 expression by siRNA in 1-mM H2O2-treated HK-2 cells decreased the Bax/Bcl-2 ratio, the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2, p38, c-Jun N-terminal kinase (JNK) 1/2, and NF-κB. In HK-2 cells, the promoter activity of NF-κB increased following H2O2 exposure, and this effect was further enhanced by APE1/Ref-1 transfection. Conclusion: The inhibition of APE1/Ref-1 with siRNA attenuated H2O2-induced apoptosis through the modulation of mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 and the nuclear activation of NF-κB and proapoptotic factors.

Purpose: Diffuse large B-cell lymphoma (DLBCL) is the most common hematologic malignancy worldwide. Although substantial improvement has been achieved by the frontline rituximab-based chemoimmunotherapy, up to 40%-50% of patients will eventually have relapsed or refractory disease, whose prognosis is extremely dismal. Materials and Methods: We have carried out two prospective cohort studies that include over 1,500 DLBCL patients treated with rituximab plus CHOP (#NCT01202448 and #NCT02474550). In the current report, we describe the outcomes of refractory DLBCL patients. Patients were defined to have refractory DLBCL if they met one of the followings, not achieving at least partial response after 4 or more cycles of R-CHOP; not achieving at least partial response after 2 or more cycles of salvage therapy; progressive disease within 12 months after autologous stem cell transplantation. Results: Among 1,581 patients, a total of 260 patients met the criteria for the refractory disease after a median time to progression of 9.1 months. The objective response rate of salvage treatment was 26.4%, and the complete response rate was 9.6%. The median overall survival (OS) was 7.5 months (95% confidence interval, 6.4 to 8.6), and the 2-year survival rate was 22.1%±2.8%. The median OS for each refractory category was not significantly different (p=0.529). Conclusion In line with the previous studies, the outcomes of refractory DLBCL patients were extremely poor, which necessitates novel approaches for this population.

Purpose: We conducted a nationwide, multicenter, prospective registry study for newly diagnosed patients with peripheral T-cell lymphoma (PTCL) to better define the clinical characteristics, treatment patterns, survival outcomes, and the role of upfront autologous stem cell transplantation (ASCT) in these patients. Materials and Methods: Patients with PTCL receiving chemotherapy with curative intent were registered and prospectively monitored. All patients were pathologically diagnosed with PTCL. Results: A total of 191 patients with PTCL were enrolled in this prospective registry study. PTCL, not otherwise specified (PTCL-NOS) was the most common pathologic subtype (n=80, 41.9%), followed by angioimmunoblastic T-cell lymphoma (AITL) (n=60, 31.4%). With a median follow-up duration of 3.9 years, the 3-year progression-free survival (PFS) and overall survival (OS) rates were 39.5% and 60.4%, respectively. The role of upfront ASCT was evaluated in patients who were considered transplant-eligible (n=59). ASCT was performed as an upfront consolidative treatment in 32 (54.2%) of these patients. There were no significant differences in PFS and OS between the ASCT and non-ASCT groups for all patients (n=59) and for patients with PTCL-NOS (n=26). However, in patients with AITL, the ASCT group was associated with significantly better PFS than the non-ASCT group, although there was no significant difference in OS. Conclusion The current study demonstrated that the survival outcomes with the current treatment options remain poor for patients with PTCL-NOS. Upfront ASCT may provide a survival benefit for patients with AITL, but not PTCL-NOS.

Background/Aims: Previous studies have reported the protective effects of tauroursodeoxycholic acid (TUDCA) on gastric epithelial cells in some animal models, but the precise mechanisms are unclear. This study examined the effects of TUDCA on NF-κB signaling in gastric epithelial cells. Moreover, the protective effects of TUDCA in experimental gastritis models induced by ethanol and NSAID were evaluated and compared with ursodeoxycholic acid (UDCA). Methods: After a pretreatment with TUDCA or UDCA, human gastric epithelial MKN-45 cells were stimulated with tumor necrosis factor (TNF)-α to activate NF-κB signaling. A real-time PCR (RT-PCR) for human interleukin (IL)-1 mRNA was performed. An electrophoretic mobility shift assay (EMSA) and immunoblot analyses were carried out. In murine models, after a pretreatment with TUDCA or UDCA, ethanol and indomethacin were administered via oral gavage. Macroscopic and microscopic assessments were performed to evaluate the preventive effects of TUDCA and UDCA on murine gastritis. Results: A pretreatment with TUDCA downregulated the IL-1α mRNA levels in MKN-45 cells stimulated with TNF-α, as assessed by RT-PCR. As determined using EMSA, a pretreatment with TUDCA reduced the TNF-α-induced NF-κB DNA binding activity. A pretreatment with TUDCA inhibited IκBα phosphorylation induced by TNF-α, as assessed by immunoblot analysis. TUDCA attenuated the ethanol-induced and NSAID-induced gastritis in murine models, as determined macroscopically and microscopically. Conclusions TUDCA inhibited NF-κB signaling in gastric epithelial cells and ameliorated ethanol- and NSAID-induced gastritis in murine models. These results support the potential of TUDCA for the prevention of gastritis in humans.