Recent studies have revealed a significant relationship between erectile dysfunction (ED) and lower urinary tract symptoms (LUTS), both of which commonly affect middle-aged and older men. These conditions share underlying causes, particularly endothelial dysfunction, atherosclerosis, and chronic pelvic ischemia (CPI). This study investigated the therapeutic potential of LDD175, a large-conductance Ca 2+ -activated K + channel (BKCa channel) opener, in simultaneously treating both conditions using a CPI animal model of male Sprague Dawley rats. Our study investigated the induction of CPI through surgical endothelial damage combined with a high-cholesterol diet. We assessed erectile and voiding functions by measuring intracavernosal pressure (ICP) and intraurethral pressure (IUP), respectively, after nerve stimulation. We performed histological examinations of vascular changes and western blot analyses of cavernous and prostate tissues to understand the underlying mechanisms. This study evaluated the effectiveness of LDD175 compared to standard treatments, such as sildenafil for ED and tamsulosin for LUTS. Therefore, the CPI model successfully demonstrated ED and LUTS symptoms with decreased ICP and increased IUP. Analysis revealed elevated levels of hypoxia-inducible factor-1α, transforming growth factor-β1 and β2 in cavernous tissue, and increased α1A-adrenoceptor expression in prostate tissue. LDD175 administration showed promising results, with dose-dependent improvements in ICP and IUP, and therapeutic effects comparable to those of established treatments. Our findings suggest a novel therapeutic approach that can simultaneously address ED and LUTS, opening new possibilities for clinical application in the treatment of these interconnected conditions.
Male ; Animals ; Erectile Dysfunction/etiology* ; Rats, Sprague-Dawley ; Lower Urinary Tract Symptoms/etiology* ; Ischemia/drug therapy* ; Rats ; Tamsulosin ; Hypoxia-Inducible Factor 1, alpha Subunit/drug effects* ; Sildenafil Citrate/therapeutic use* ; Penis/blood supply* ; Disease Models, Animal ; Transforming Growth Factor beta1/metabolism* ; Pelvis/blood supply* ; Prostate/metabolism* ; Sulfonamides/therapeutic use* ; Large-Conductance Calcium-Activated Potassium Channels/agonists*

Background: and Purpose Treatments for neuromyelitis optica spectrum disorder (NMOSD) such as eculizumab, ravulizumab, satralizumab, and inebilizumab have significantly advanced relapse prevention, but they remain expensive. Rituximab is an off-label yet popular alternative that offers a cost-effective solution, but its real-world efficacy needs better quantification for guiding the application of newer approved NMOSD treatments (ANTs). This study aimed to determine real-world rituximab failure rates to anticipate the demand for ANTs and aid in resource allocation. Methods: We conducted a nationwide retrospective study involving 605 aquaporin-4-antibody-positive NMOSD patients from 22 centers in South Korea that assessed the efficacy and safety of rituximab over a median follow-up of 47 months. Results: The 605 patients treated with rituximab included 525 (87%) who received continuous therapy throughout the follow-up period (median=47 months, interquartile range=15–87 months). During this period, 117 patients (19%) experienced at least 1 relapse. Notably, 68 of these patients (11% of the total cohort) experienced multiple relapses or at least 1 severe relapse.Additionally, 2% of the patients discontinued rituximab due to adverse events, which included severe infusion reactions, neutropenia, and infections. Conclusions This study has confirmed the efficacy of rituximab in treating NMOSD, as evidenced by an 87% continuation rate among patients over a 4-year follow-up period. Nevertheless, the occurrence of at least one relapse in 19% of the cohort, including 11% who experienced multiple or severe relapses, and a 2% discontinuation rate due to adverse events highlight the urgent need for alternative therapeutic options.

Purpose: To assess the effectiveness of the prostate health index (PHI) in patients with no index lesions on multiparametric magnetic resonance imaging (mpMRI) or with negative findings on past prostate biopsy if there was an index lesion on mpMRI. Materials and Methods: Patients without an index lesion on MRI or with a negative result on combined biopsy for index lesions were assessed. Patients who underwent transperineal mapping biopsy among those suspected of having prostate cancer (PCa) due to persistently elevated prostate-specific antigen (PSA) levels were analyzed. Results: Of the 291 patients, 82 (28.2%) were diagnosed with PCa. Sixty-five of 291 patients had negative finding in previous combined biopsy. In total, 226 patients did not have any index lesions. The mean age of the PCa group was 64.33±8.88 years and that of the non-cancer group was 59.88±10.26 years (p<0.001). The PHI was 46.75±28.22 in the PCa group and 37.74±17.37 in the noncancer group (p=0.001), and the prostate volume was 41.52±15.77 mL in the PCa group and 50.78±23.97 mL in the non-cancer group (p=0.001). In multivariate analysis, age (odds ratio [OR] 1.096, p<0.001), PHI (OR 1.021, p=0.005), and prostate volume (OR 0.954, p<0.001) were identified as significant factors for PCa detection. The optimal cutoff value of the PHI for PCa detection was 44.6 and the PHI density (PHID) was 0.88. Conclusions In patients with elevated PSA levels but no index lesions on mpMRI or negative biopsy findings, PHI and PHID demonstrated significant potential for improving PCa detection.

Background: Active surveillance (AS) has emerged as a viable management strategy for low-risk papillary thyroid microcarcinoma (PTMC), following pioneering trials at Kuma Hospital and the Cancer Institute Hospital in Japan. Numerous prospective cohort studies have since validated AS as a management option for low-risk PTMC, leading to its inclusion in thyroid cancer guidelines across various countries. From 2016 to 2020, the Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro) enrolled 1,177 patients, providing comprehensive data on PTMC progression, sonographic predictors of progression, quality of life, surgical outcomes, and cost-effectiveness when comparing AS to immediate surgery. The second phase of MAeSTro (MAeSTro-EXP) expands AS to low-risk papillary thyroid carcinoma (PTC) tumors larger than 1 cm, driven by the hypothesis that overall risk assessment outweighs absolute tumor size in surgical decision-making. Methods: This protocol aims to address whether limiting AS to tumors smaller than 1 cm may result in unnecessary surgeries for low-risk PTCs detected during their rapid initial growth phase. By expanding the AS criteria to include tumors up to 1.5 cm, while simultaneously refining and standardizing the criteria for risk assessment and disease progression, we aim to minimize overtreatment and maintain rigorous monitoring to improve patient outcomes. Conclusion This study will contribute to optimizing AS guidelines and enhance our understanding of the natural course and appropriate management of low-risk PTCs. Additionally, MAeSTro-EXP involves a multinational collaboration between South Korea and Australia. This cross-country study aims to identify cultural and racial differences in the management of low-risk PTC, thereby enriching the global understanding of AS practices and their applicability across diverse populations.

Emerging evidence suggests that systemic inflammation may play a critical role in neurological disorders. Recent studies have shown the connection between inflammatory bowel diseases (IBD) and neurological disorders, revealing a bidirectional relationship through the gut-brain axis.Immunotherapies, such as Treg cells infusion, have been proposed for IBD. However, the role of adaptive immune cells in IBD-induced neuroinflammation remains unclear. In this study, we established an animal model for IBD in mice with severe combined immune-deficient (SCID), an adaptive immune deficiency, to investigate the role of adaptive immune cells in IBD-induced neuroinflammation. Mice were fed 1%, 3%, or 5% dextran sulfate sodium (DSS) for 5 days. We measured body weight, colon length, disease activity index (DAI), and crypt damage. Pro-inflammatory cytokines were measured in the colon, while microglial morphology, neuronal count, and inflammatory cytokines were analyzed in the brain. In the 3% DSS group, colitis symptoms appeared at day 7, with reduced colon length and increased crypt damage showing colitis-like symptoms. By day 21, colon length and crypt damage persisted, while DAI showed recovery. Although colonic inflammation peaked at day 7, no significant increase in inflammatory cytokines or microglial hyperactivation was observed in the brain. By day 21, neuroinflammation was detected, albeit with a slight delay, in the absence of adaptive immune cells. The colitis-induced neuroinflammation model provides insights into the fundamental immune mechanisms of the gut-brain axis and may contribute to developing immune cell therapies for IBD-induced neuroinflammation.

Background/Aims: This study aimed to evaluate the performance of the Model for End-Stage Liver Disease (MELD) 3.0 for predicting mortality and liver-related complications compared with the Child-Pugh classification, albumin-bilirubin (ALBI) grade, the MELD, and the MELD sodium (MELDNa) score. Methods: We evaluated a multicenter retrospective cohort of incorporated patients with cirrhosis between 2013 and 2019. We conducted comparisons of the area under the receiver operating characteristic curve (AUROC) of the MELD3.0 and other models for predicting 3-month mortality. Additionally, we assessed the risk of cirrhosis-related complications according to the MELD3.0 score. Results: A total of 3,314 patients were included. The mean age was 55.9±11.3 years, and 70.2% of the patients were male. Within the initial 3 months, 220 patients (6.6%) died, and the MELD3.0had the best predictive performance among the tested models, with an AUROC of 0.851, outperforming the Child-Pugh classification, ALBI grade, MELD, and MELDNa. A high MELD3.0score was associated with an increased risk of mortality. Compared with that of the group with a MELD3.0 score <10 points, the adjusted hazard ratio of the group with a score of 10–20 pointswas 2.176, and that for the group with a score of ≥20 points was 4.892. Each 1-point increase inthe MELD3.0 score increased the risk of cirrhosis-related complications by 1.033-fold. The risk of hepatorenal syndrome showed the highest increase, with an adjusted hazard ratio of 1.149, followed by hepatic encephalopathy and ascites. Conclusions The MELD3.0 demonstrated robust prognostic performance in predicting mortality in patients with cirrhosis. Moreover, the MELD3.0 score was linked to cirrhosis-related complications, particularly those involving kidney function, such as hepatorenal syndrome and ascites.

Purpose: This study aimed to compare the wound cosmesis of a single-incision approach on scar assessment after laparoscopic surgery for colon cancer. Methods: This study included 32 patients undergoing single-port laparoscopic surgery (SPLS) and 61 patients undergoing multiport laparoscopic surgery (MPLS) for colon cancer at 3 tertiary referral hospitals between September 2011 and December 2019. We modified and applied the Korean version of the Patient and Observer Scar Assessment Scale (POSAS) to assess cosmetic outcomes. To assess the interobserver reliability using intraclass correlation coefficient values for the Observer Scar Assessment Scale (OSAS), the surgeons evaluated 5 images of postoperative scars. Results: No significant differences were observed in the time before the return of normal bowel function, time to sips of water and soft diet initiation, length of in-hospital stay, and postoperative complication rate. The SPLS group had a shorter total incision length than the MPLS group. The POSAS favored the SPLS approach, revealing significant differences in the Patient Scar Assessment Scale (PSAS), OSAS, and overall scores. The SPLS approach was an independent factor influencing the POSAS, PSAS, and OSAS scores. Eleven colorectal surgeons had a significantly substantial intraclass coefficient. Conclusion The cosmetic outcomes of SPLS as assessed by the patients and surgeons were superior to those of MPLS in colon cancer. Reducing the number of ports is an independent factor affecting scar assessment by patients and observers.

Purpose: This study aimed to compare the wound cosmesis of a single-incision approach on scar assessment after laparoscopic surgery for colon cancer. Methods: This study included 32 patients undergoing single-port laparoscopic surgery (SPLS) and 61 patients undergoing multiport laparoscopic surgery (MPLS) for colon cancer at 3 tertiary referral hospitals between September 2011 and December 2019. We modified and applied the Korean version of the Patient and Observer Scar Assessment Scale (POSAS) to assess cosmetic outcomes. To assess the interobserver reliability using intraclass correlation coefficient values for the Observer Scar Assessment Scale (OSAS), the surgeons evaluated 5 images of postoperative scars. Results: No significant differences were observed in the time before the return of normal bowel function, time to sips of water and soft diet initiation, length of in-hospital stay, and postoperative complication rate. The SPLS group had a shorter total incision length than the MPLS group. The POSAS favored the SPLS approach, revealing significant differences in the Patient Scar Assessment Scale (PSAS), OSAS, and overall scores. The SPLS approach was an independent factor influencing the POSAS, PSAS, and OSAS scores. Eleven colorectal surgeons had a significantly substantial intraclass coefficient. Conclusion The cosmetic outcomes of SPLS as assessed by the patients and surgeons were superior to those of MPLS in colon cancer. Reducing the number of ports is an independent factor affecting scar assessment by patients and observers.

Purpose: This study aimed to define an optimal age cutoff for early-onset gastric cancer (EOGC) and compare its characteristics with those of late-onset gastric cancer (LOGC) using nationwide survey data. Methods: Using data from a nationwide survey, this comprehensive population-based study analyzed data spanning 3 years (2009, 2014, and 2019). The joinpoint analysis and interrupted time series (ITS) methodology were employed to identify age cutoffs for EOGC based on the sex ratio and tumor histology. Clinicopathologic characteristics and surgical outcomes were compared between the EOGC and LOGC groups. Results: The age cutoff for defining EOGC was suggested to be 50 years, supported by joinpoint and ITS analyses. Early gastric cancer was predominantly present in the EOGC and LOGC groups. Patients with EOGC comprised 20.3% of the total study cohort and demonstrated a more advanced disease stage compared to patients with LOGC. However, patients with EOGC underwent more minimally invasive surgeries, experienced shorter hospital stays, and had lower postoperative morbidity and mortality rates. Conclusion This study proposes an age of ≤50 years as a criterion for defining EOGC and highlights its features compared to LOGC. Further research using this criterion should guide tailored treatment strategies and improve outcomes for young patients with gastric cancer.