Purpose: Although the mechanism underlying interstitial cystitis/bladder pain syndrome (IC/BPS) remains unclear, oxidative stress is suggested to be implicated in IC/BPS development. Sea buckthorn (SB; Hippophae rhamnoides L.) contains several compounds with antioxidant properties. In addition, intravesical application of hydrochloric acid (HCl) in rats induces histological changes similar to those observed in humans with IC. Therefore, the aim of this study was to evaluate the anti-inflammatory effects of SB in an HCl-induced rat cystitis model. Materials and Methods: Twenty 8-week-old female Sprague–Dawley rats were instilled with HCl in their bladders to create an IC/BPS model. The model rats were divided into three groups and orally administrated distilled water (control, n=4), concentrated SB (n=8), or pentosan polysulfate (PPS, n=8) daily. Pathologic inflammation grade (H&E staining), number of mast cells per square millimeter (toluidine blue staining), fibrotic changes (Masson’s trichrome staining), and apoptosis (terminal deoxynucleotidyl transferase dUTP nick end labeling staining) of bladder tissue samples were compared among the groups. Results: Compared to the control group, the SB and PPS groups showed reduced edema (5.25±0.96 vs. 2.25±0.46 vs. 2.50±0.54, p=0.004, p=0.005, respectively), number of mast cells (12.5±3.6 vs. 6.8±1.9 vs. 6.6±1.8, p=0.010, p=0.002, respectively), ratio of fibrotic submucosal tissue (63.9%±7.0% vs. 43.6%±9.9% vs. 40.5%±5.2%, p<0.001, p<0.001, respectively), and ratio of apoptotic nucleus (40.7%±11.7% vs. 7.7%±6.5% vs. 5.1%±4.9%, p<0.001, p<0.001, respectively). Conclusions SB exhibited anti-inflammatory effects comparable to those of PPS in the HCl-induced chemical cystitis model.

Background: Late-onset hypogonadism (LOH) is associated with reduced testosterone levels and an increase in various physical, mental, and emotional changes in men with age. Several lifestyle factors, including smoking, are reported to be related to LOH; however, very few studies have sufficiently investigated the relationships between smoking and the symptoms of LOH. This study aimed to use the Androgen Deficiency in Aging Males (ADAM) questionnaire to assess the associations between smoking and LOH symptoms in Korean men. Methods: Men who underwent medical check-ups and transrectal ultrasonography at a university hospital between January 1, 2018 and March 31, 2021 (n=793) were included in this study. Multiple logistic regression was used to assess the risk of LOH symptoms among non-smokers, exsmokers, and current smokers, with adjustments for age, body mass index, alcohol consumption, and exercise and education levels. Results: There were significant correlations between LOH symptoms, as assessed using the ADAM questionnaire, and smoking status. The results of the multivariate logistic regression analysis adjusted for confounding factors indicated that the risk of LOH symptoms was higher in the ex-smokers (odds ratio, 2.446; 95% confidential interval, 1.511–3.962) and current smokers (odds ratio, 6.664; 95% confidential interval, 3.485–12.74) groups. Conclusion These results indicate a positive correlation between smoking and LOH symptoms in Korean men. Nevertheless, large-scale studies are required to further validate these findings.

Background: Late-onset hypogonadism (LOH) is associated with reduced testosterone levels and an increase in various physical, mental, and emotional changes in men with age. Several lifestyle factors, including smoking, are reported to be related to LOH; however, very few studies have sufficiently investigated the relationships between smoking and the symptoms of LOH. This study aimed to use the Androgen Deficiency in Aging Males (ADAM) questionnaire to assess the associations between smoking and LOH symptoms in Korean men. Methods: Men who underwent medical check-ups and transrectal ultrasonography at a university hospital between January 1, 2018 and March 31, 2021 (n=793) were included in this study. Multiple logistic regression was used to assess the risk of LOH symptoms among non-smokers, exsmokers, and current smokers, with adjustments for age, body mass index, alcohol consumption, and exercise and education levels. Results: There were significant correlations between LOH symptoms, as assessed using the ADAM questionnaire, and smoking status. The results of the multivariate logistic regression analysis adjusted for confounding factors indicated that the risk of LOH symptoms was higher in the ex-smokers (odds ratio, 2.446; 95% confidential interval, 1.511–3.962) and current smokers (odds ratio, 6.664; 95% confidential interval, 3.485–12.74) groups. Conclusion These results indicate a positive correlation between smoking and LOH symptoms in Korean men. Nevertheless, large-scale studies are required to further validate these findings.

Background: Late-onset hypogonadism (LOH) is associated with reduced testosterone levels and an increase in various physical, mental, and emotional changes in men with age. Several lifestyle factors, including smoking, are reported to be related to LOH; however, very few studies have sufficiently investigated the relationships between smoking and the symptoms of LOH. This study aimed to use the Androgen Deficiency in Aging Males (ADAM) questionnaire to assess the associations between smoking and LOH symptoms in Korean men. Methods: Men who underwent medical check-ups and transrectal ultrasonography at a university hospital between January 1, 2018 and March 31, 2021 (n=793) were included in this study. Multiple logistic regression was used to assess the risk of LOH symptoms among non-smokers, exsmokers, and current smokers, with adjustments for age, body mass index, alcohol consumption, and exercise and education levels. Results: There were significant correlations between LOH symptoms, as assessed using the ADAM questionnaire, and smoking status. The results of the multivariate logistic regression analysis adjusted for confounding factors indicated that the risk of LOH symptoms was higher in the ex-smokers (odds ratio, 2.446; 95% confidential interval, 1.511–3.962) and current smokers (odds ratio, 6.664; 95% confidential interval, 3.485–12.74) groups. Conclusion These results indicate a positive correlation between smoking and LOH symptoms in Korean men. Nevertheless, large-scale studies are required to further validate these findings.

Background: Late-onset hypogonadism (LOH) is associated with reduced testosterone levels and an increase in various physical, mental, and emotional changes in men with age. Several lifestyle factors, including smoking, are reported to be related to LOH; however, very few studies have sufficiently investigated the relationships between smoking and the symptoms of LOH. This study aimed to use the Androgen Deficiency in Aging Males (ADAM) questionnaire to assess the associations between smoking and LOH symptoms in Korean men. Methods: Men who underwent medical check-ups and transrectal ultrasonography at a university hospital between January 1, 2018 and March 31, 2021 (n=793) were included in this study. Multiple logistic regression was used to assess the risk of LOH symptoms among non-smokers, exsmokers, and current smokers, with adjustments for age, body mass index, alcohol consumption, and exercise and education levels. Results: There were significant correlations between LOH symptoms, as assessed using the ADAM questionnaire, and smoking status. The results of the multivariate logistic regression analysis adjusted for confounding factors indicated that the risk of LOH symptoms was higher in the ex-smokers (odds ratio, 2.446; 95% confidential interval, 1.511–3.962) and current smokers (odds ratio, 6.664; 95% confidential interval, 3.485–12.74) groups. Conclusion These results indicate a positive correlation between smoking and LOH symptoms in Korean men. Nevertheless, large-scale studies are required to further validate these findings.

Purpose: This study aimed to investigate the incidence and risk factors for secondary malignant neoplasms (SMN) in pediatric solid tumors, focusing on the effects of tandem high-dose chemotherapy (HDCT). Materials and Methods: Patients (aged < 19 years) diagnosed with or treated for pediatric solid tumors between 1994 and 2014 were retrospectively analyzed. The cumulative incidence of SMN was estimated using competing risk methods by considering death as a competing risk. Results: A total of 1,435 patients (413 with brain tumors and 1,022 with extracranial solid tumors) were enrolled. Seventy-one patients developed 74 SMNs, with a 10-year and 20-year cumulative incidence of 2.680±0.002% and 10.193±0.024%, respectively. The types of SMN included carcinoma in 28 (37.8%), sarcoma in 24 (32.4%), and hematologic malignancy in 15 (20.3%) cases. Osteosarcoma and thyroid carcinoma were the most frequently diagnosed tumors. Multivariate analysis showed that radiotherapy (RT) > 2, 340 cGy, and tandem HDCT were significant risk factors for SMN development. The SMN types varied according to the primary tumor type; carcinoma was the most frequent SMN in brain tumors and neuroblastoma, whereas hematologic malignancy and sarcomas developed more frequently in patients with sarcoma and retinoblastoma, respectively. Conclusion The cumulative incidence of SMN in pediatric patients with solid tumors was considerably high, especially in patients who underwent tandem HDCT or in those who received RT > 2,340 cGy. Therefore, the treatment intensity should be optimized based on individual risk assessment and the long-term follow-up of pediatric cancer survivors.

Purpose: Overactive bladder (OAB) is observed in women with functional bladder outlet obstruction (FBOO), as are lower urinary tract symptoms (LUTS). Therefore, we evaluated the urodynamic characteristics of women with storage LUTS and FBOO diagnosed by urodynamic studies (UDS). Methods: Women (n=108) with storage LUTS and FBOO diagnosed by UDS were included in this study. The urodynamic characteristics of women with FBOO were compared with those of women with OAB (n=34) and stress urinary incontinence (SUI, n=78). FBOO was defined as a maximum flow rate (Qmax) < 15 mL/sec, combined with detrusor pressure at a Qmax (PdetQmax) > 20 cm H2O in a pressure-flow study. The UDS included uroflowmetry, postvoid residual volume determination, a cystometrogram, and a pressure-flow study. Results: Women with FBOO who had storage symptoms showed a higher PdetQmax and maximum urethral closing pressure (MUCP) than women with OAB and SUI. Interstitial cystitis/bladder pain syndrome (IC/BPS) was observed in 17.6% of women with FBOO. MUCP was significantly higher in women with BOO than in women with BOO and IC/BPS (115.6±27.4 and 96.6±14.1 cm H2O, P=0.00). The receiver operating characteristic curve analysis showed that the cutoff values of MUCP in women with FBOO compared to women with OAB and SUI were 87 cm H2O (sensitivity=81.5%, specificity=73.5%) and 36 cm H2O (sensitivity=92.6%, specificity=84.4%), respectively. The cutoff value of MUCP in women with FBOO compared to women with FBOO and IC/BPS was 92 cm H2O (sensitivity=85.4%, specificity=78.9%). Conclusions MUCP could have predictive value for identifying FBOO in women with complex LUTS.

Purpose: DA-8010 is a novel muscarinic M3 receptor antagonist with significant selectivity for bladder over salivary gland in preclinical studies. We evaluated the clinical efficacy and safety of DA-8010 in overactive bladder (OAB) patients. Methods: This phase 2, randomized, double-blind, parallel-group, active reference- and placebo-controlled trial was conducted at 12 centers in South Korea (NCT03566134). Patients aged ≥19 years with OAB symptoms for ≥3 months were enrolled. Three hundred six patients (30.07% male) were randomized to 12 weeks of treatment among 4 groups; 2 experimental groups (DA-8010 2.5 or 5 mg), an active reference group (solifenacin 5 mg), and a placebo group. The change from the baseline of (=∆) 24-hour frequency at 12 weeks (primary endpoint), episodes of urgency, overall/urgency urinary incontinence, average/ maximum voided volume, nocturia, and patients’ subjective responses were analyzed. Results: In the full analysis set, the mean (standard deviation) [median] values for ∆ 24-hour frequency at 12 weeks were -1.01 (2.44) [-1.33] for placebo, -1.22 (2.05) [-1.33] for DA-8010 2.5 mg, and -1.67 (2.25) [-1.67] for DA-8010 5 mg; DA-8010 5 mg showed a significant decrease compared with placebo (P=0.0413). At 4 and 8 weeks, both DA-8010 2.5 mg (P=0.0391 at 4 weeks, P=0.0335 at 8 weeks) and DA-8010 5 mg (P=0.0001 at 4 weeks, P=0.0210 at 8 weeks) showed significant decrease in ∆ 24-hour frequency compared with placebo. DA-8010 5 mg achieved a significant decrease in ∆ number of urgency episodes, compared with placebo at 4 (P=0.0278) and 8 (P=0.0092) weeks. Adverse drug reactions (ADRs) were observed in 3.95% of placebo, 6.67% of DA-8010 2.5 mg, 18.42% of DA-8010 5 mg, and 17.33% of solifenacin 5 mg groups. No serious ADRs were observed in any patient. Conclusions Both DA-8010 2.5 mg and 5 mg showed therapeutic efficacy for OAB without serious ADRs. Therefore, both dosages of DA-8010 can advance to a subsequent large-scale phase 3 trial.

Suppressors of cytokine signaling (SOCS) have emerged as potential regulators of macrophage function. We have investigated mechanisms of SOCS3 action on type 2 macrophage (M2) differentiation induced by glucocorticoid using human monocytic cell lines and mouse bone marrow-derived macrophages. Treatment of THP1 monocytic cells with dexamethasone (Dex) induced ROS generation and M2 polarization promoting IL-10 and TGF-β production, while suppressing IL-1β, TNF-α and IL-6 production. SOCS3 over-expression reduced, whereas SOCS3 ablation enhanced IL-10 and TGF-β induction with concomitant regulation of ROS. As a mediator of M2 differentiation, glucocorticoidinduced leucine zipper (GILZ) was down-regulated by SOCS3 and up-regulated by shSOCS3. The induction of GILZ and IL-10 by Dex was dependent on ROS and p38 MAPK activity. Importantly, GILZ ablation led to the inhibition of ROS generation and anti-inflammatory cytokine induction by Dex. Moreover, GILZ knock-down negated the up-regulation of IL-10 production induced by shSOCS3 transduction. Our data suggest that SOCS3 targets ROS- and p38-dependent GILZ expression to suppress Dex-induced M2 polarization.

Purpose: Effectiveness and safety of clofarabine (one of the treatment mainstays in pediatric patients with relapsed/refractory acute lymphoblastic leukemia [ALL]) was assessed in Korean pediatric patients with ALL to facilitate conditional coverage with evidence development. Materials and Methods: In this multicenter, prospective, observational study, patients receiving clofarabine as mono/combination therapy were followed up every 4-6 weeks for 6 months or until hematopoietic stem cell transplantation (HSCT). Response rates, survival outcomes, and adverse events were assessed. Results: Sixty patients (2-26 years old; 65% B-cell ALL, received prior ≥ 2 regimen, 68.3% refractory to previous regimen) were enrolled and treated with at least one dose of clofarabine; of whom 26 (43.3%) completed 6 months of follow-up after the last dose of clofarabine. Fifty-eight patients (96.7%) received clofarabine combination therapy. Overall remission rate (complete remission [CR] or CR without platelet recovery [CRp]) was 45.0% (27/60; 95% confidence interval [CI], 32.4 to 57.6) and the overall response rate (CR, CRp, or partial remission [PR]) was 46.7% (28/60; 95% CI, 34.0 to 59.3), with 11 (18.3%), 16 (26.7%), and one (1.7%) patients achieving CR, CRp, and PR, respectively. The median time to remission was 5.1 weeks (95% CI, 4.7 to 6.1). Median duration of remission was 16.6 weeks (range, 2.0 to 167.6 weeks). Sixteen patients (26.7%) proceeded to HSCT. There were 24 deaths; 14 due to treatment-emergent adverse events. Conclusion Remission with clofarabine was observed in approximately half of the study patients who had overall expected safety profile; however, there was no favorable long-term survival outcome in this study.