Purpose: Radical cystectomy (RC) is associated with substantial postoperative morbidity, and unplanned readmission remains common despite advances in perioperative management. However, the association between postoperative readmission due to complications and oncologic outcomes after RC for bladder cancer has not been clearly defined. We evaluated the impact of postoperative readmission on overall survival (OS) and cancer-specific survival (CSS) after RC for bladder cancer. Materials and Methods: We retrospectively analyzed 3,972 patients who underwent RC for bladder cancer in a multicenter cohort. Postoperative readmission was defined as unplanned hospitalization within 90 days postsurgery due to surgery-related complications. Survival outcomes were assessed using the Kaplan-Meier method and compared using the log-rank test. Univariable and multivariable Cox proportional hazards regression analyses were performed to identify independent predictors of OS and CSS. Results: Among the study population, 916 patients (23.1%) experienced postoperative readmission. Baseline and perioperative characteristics were generally comparable between patients with and without readmission. Kaplan-Meier analyses demonstrated significantly worse OS and CSS among patients who experienced postoperative readmission (both log-rank p<0.001). In multivariable analyses adjusting for clinicopathological factors, postoperative readmission remained independently associated with worse OS (hazard ratio [HR], 1.654; 95% confidence interval [CI], 1.464–1.868; p<0.001) and CSS (HR, 1.761; 95% CI, 1.509–2.055; p<0.001). Conclusion Postoperative readmission within 90 days after RC was independently associated with inferior long-term oncologic outcomes. These findings suggest the importance of strategies aimed at preventing postoperative complications and subsequent readmission.

Purpose: Although bladder cancer occurs three to 4 times more frequently in men than in women, the relative number of deaths compared to incidence is higher in women, suggesting that women have a worse prognosis than men. Emerging evidence indicates that the activity of the sex steroid hormone pathway may play a role in bladder cancer development, with demonstrations that both androgens and estrogens have biological effects on bladder cancer in vitro and in vivo. This study investigates the influence of sex and menopausal status on recurrence and cancer-specific death (CSD) in bladder cancer patients undergoing radical cystectomy (RC). Materials and Methods: This retrospective analysis included 3,913 patients from the Korean Bladder Cancer Study Group Database who underwent RC between 2010 and 2019. Patients were categorized based on gender and menopausal status (≤50 years: premenopausal; >50 years: postmenopausal). Pathological factors, neoadjuvant chemotherapy, recurrence, and CSD rates were analyzed using chi-square and Fisher exact tests. Results: Among the 3,913 patients, 400 (10.2%) were female. Premenopausal females exhibited significantly lower recurrence rates (28.6%) compared to postmenopausal females (45.7%). CSD rates were similarly reduced in premenopausal females (12.0% vs. 22.2% in postmenopausal females). No significant sex differences in recurrence or CSD were observed among premenopausal patients. Pathological T stage, nodal status, and lymphovascular invasion were significantly associated with recurrence in males, while nodal status alone was significant in females. Neoadjuvant chemotherapy was significantly more frequently administered to male patients under the age of 50, while no difference was observed in the administration of neoadjuvant chemotherapy among female patients based on menopausal status. Conclusion Hormonal changes associated with menopause significantly influence bladder cancer outcomes in women. Premenopausal hormonal environments seem protective, underscoring the need for further research into hormone-driven mechanisms in bladder cancer.

Purpose: This study aimed to evaluate the prognostic value of a trifecta, defined as negative soft tissue surgical margin (STSM), removal of ≥16 lymph nodes, and absence of major complications (Clavien-Dindo classification grade >III) within 90 days, after radical cystectomy (RC), using a large multicenter cohort. Materials and Methods: We retrospectively analyzed data from 3,972 patients with bladder cancer who underwent RC at 11 tertiary centers in South Korea between 2003 and 2024. Survival outcomes, including overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS), were compared according to trifecta status using Kaplan-Meier and Cox regression analyses. Propensity score matching was performed to adjust for baseline differences. Results: A total of 2,014 eligible patients were included in the final analysis, and the trifecta was achieved in 47.8%. Kaplan-Meier analysis demonstrated significantly improved 5- and 10-year OS (66.7% vs. 62.0%; 62.9% vs. 57.2%; p=0.002), CSS (79.3% vs. 75.4%; 77.8% vs. 73.8%; p=0.008), and RFS (62.7% vs. 57.6%; 60.8% vs. 55.2%; p=0.001) in the trifecta group. In multivariable analysis, trifecta achievement was significantly associated with better OS (HR, 0.813; p=0.008), CSS (HR, 0.787; p=0.017), and RFS (HR, 0.844; p=0.036). Among individual components, negative STSM showed the strongest prognostic effect across all endpoints. Conclusions In this large multicenter study, patients who achieved the RC trifecta exhibited significantly superior survival outcomes compared with those who did not. The trifecta may serve as a practical and standardized metric for assessing surgical quality and performance in RC. Future prospective studies are warranted to validate its prognostic and quality-assurance utility.

IMMUNE MODULATORY EFFECT OF HYPERTHERMIA DURING TREATMENT OF RECURRENT, METASTATIC OR LOCALLY ADVANCED SOLID ORGAN MALIGNANCIES Background: The use of hyperthermia as an adjunct to improve conventional therapies in multimodal cancer treatment is supported by an increasing body of research. The underlying biological contribution of hyperthermia in modulating the cells of the immune system has been a growing area of interest. This study aims to evaluate the immune modulatory effect of locoregional hyperthermia given with standard of care treatment for patients with recurrent or metastatic solid malignancies. Secondary endpoints were tolerability, change in pain score and quality of life, and tumour control rate. Methods: A single-centre prospective study, conducted from December 2019 to December 2021 at the University of Malaya Medical Centre, recruited 30 patients with solid organ malignancy at baseline. Alongside standard cancer treatment, patients also received hyperthermia treatment for 2 hours, two or three times a week for up to 16-weeks using REMISSION1ºC hyperthermia-induction device. Flow cytometry for lymphocyte enumeration and immunophenotyping was done on blood samples collected from patients at 4 different time points (Baseline, week 1 post hyperthermia, week 1 post standard therapy, week 4. Results: In the analysis of lymphocyte subsets, an increase in CD8+ central memory T cells between baseline and week 1 post hyperthermia (Mean: Baseline 3.854, Week 1A 5.818; P = 0.013) was noted. An increase of CD4+ effector memory T cells between baseline and week 4 post hyperthermia in conjunction with standard therapy (Mean: Baseline 33.60, Week 4 39.34; P = 0.022) was recorded. There was also a marked increase in the percentage of CD8+ T cell expressing checkpoint inhibitory marker PD-1 post week 1 hyperthermia treatment (Mean: Baseline 7.439, week 1A 9.757; P = 0.048) as well as post standard treatment (Mean: Baseline 7.439, Week 1B 9.222; P = 0.033) from baseline. Conclusion: Hyperthermia produced significant effects on the immune cell profiles of cancer patients on treatment. The subset of CD4 effector memory T cells increased significantly, although there was also sign of increased T cells exhaustion. These findings serve as a stepping stone for further research in exploring the mechanisms of hyperthermia in immune modulation and also its translation into clinical practice.

Background: This study evaluated the efficacy and safety of add-on gemigliptin in patients with type 2 diabetes mellitus (T2DM) who had inadequate glycemic control with metformin and dapagliflozin. Methods: In this randomized, placebo-controlled, parallel-group, double-blind, phase III study, 315 patients were randomized to receive either gemigliptin 50 mg (n=159) or placebo (n=156) with metformin and dapagliflozin for 24 weeks. After the 24-week treatment, patients who received the placebo were switched to gemigliptin, and all patients were treated with gemigliptin for an additional 28 weeks. Results: The baseline characteristics were similar between the two groups, except for body mass index. At week 24, the least squares mean difference (standard error) in hemoglobin A1c (HbA1c) changes was –0.66% (0.07) with a 95% confidence interval of –0.80% to –0.52%, demonstrating superior HbA1c reduction in the gemigliptin group. After week 24, the HbA1c level significantly decreased in the placebo group as gemigliptin was administered, whereas the efficacy of HbA1c reduction was maintained up to week 52 in the gemigliptin group. The safety profiles were similar: the incidence rates of treatment-emergent adverse events up to week 24 were 27.67% and 29.22% in the gemigliptin and placebo groups, respectively. The safety profiles after week 24 were similar to those up to week 24 in both groups, and no new safety findings, including hypoglycemia, were noted. Conclusion Add-on gemigliptin was well tolerated, providing comparable safety profiles and superior efficacy in glycemic control over placebo for long-term use in patients with T2DM who had poor glycemic control with metformin and dapagliflozin.

Background: This study focuses on the establishment and operation of a stroke patient hotline program to help patients and their caregivers determine when acute neurological changes require emergency attention.Method: The stroke hotline was established at the Gyeonggi Regional Cerebrovascular Center, Seoul National University Bundang Hospital, in June 2016. Patients diagnosed with stroke during admission or in outpatient clinics were registered and provided with stroke education. Consulting nurses managed hotline calls and made decisions about outpatient schedules or emergency room referrals, consulting physicians when necessary. The study analyzed consultation records from June 2016 to December 2020, assessing consultation volumes and types. Outcomes and hotline satisfaction were also evaluated. Results: Over this period, 6,851 patients were registered, with 1,173 patients (18%) undergoing 3,356 hotline consultations. The average monthly consultation volume increased from 29.2 cases in 2016 to 92.3 cases in 2020. Common consultation types included stroke symptoms (22.3%), blood pressure/glucose inquiries (12.8%), and surgery/procedure questions (12.6%). Unexpected outpatient visits decreased from 103 cases before the hotline to 81 cases after. Among the 2,244 consultations between January 2019 and December 2020, 9.6% were recommended hospital visits, with two cases requiring intra-arterial thrombectomy. Patient satisfaction ratings of 9–10 points increased from 64% in 2019 to 69% in 2020. Conclusion The stroke hotline program effectively reduced unexpected outpatient visits and achieved high patient satisfaction.Expanding the program could enhance the management of stroke-related neurological symptoms and minimize unnecessary healthcare resource utilization.

Purpose: Epidermal growth factor receptor kinase domain duplication (EGFR-KDD) is a rare and poorly understood oncogenic mutation in non–small cell lung cancer (NSCLC). We aimed to investigate the acquired resistance mechanism of EGFR-KDD against EGFR-TKIs. Materials and Methods: We identified EGFR-KDD in tumor tissue obtained from a patient with stage IV lung adenocarcinoma and established the patient-derived cell line SNU-4784. We also established several EGFR-KDD Ba/F3 cell lines: EGFR-KDD wild type (EGFR-KDDWT), EGFR-KDD domain 1 T790M (EGFR-KDDD1T), EGFR-KDD domain 2 T790M (EGFR-KDDD2T), and EGFR-KDD both domain T790M (EGFR-KDDBDT). We treated the cells with EGFR tyrosine kinase inhibitors (TKIs) and performed cell viability assays, immunoblot assays, and ENU (N-ethyl-N-nitrosourea) mutagenesis screening. Results: In cell viability assays, SNU-4784 cells and EGFR-KDDWT Ba/F3 cells were sensitive to 2nd generation and 3rd generation EGFR TKIs. In contrast, the T790M-positive EGFR-KDD Ba/F3 cell lines (EGFR-KDDT790M) were only sensitive to 3rd generation EGFR TKIs. In ENU mutagenesis screening, we identified the C797S mutation in kinase domain 2 of EGFR-KDDBDT Ba/F3 cells. Based on this finding, we established an EGFR-KDD domain 1 T790M/domain 2 cis-T790M+C797S (EGFR-KDDT/T+C) Ba/F3 model, which was resistant to EGFR TKIs and anti-EGFR monoclonal antibody combined with EGFR TKIs. Conclusion Our study reveals that the T790M mutation in EGFR-KDD confers resistance to 1st and 2nd generation EGFR TKIs, but is sensitive to 3rd generation EGFR TKIs. In addition, we identified that the C797S mutation in kinase domain 2 of EGFR-KDDT790M mediates a resistance mechanism against 3rd generation EGFR TKIs.

Objective: : While balanced crystalloid (BC) could be a relevant fluid regimen with buffer system compared with normal saline (NS), there have been no studies on the optimal fluid for surgery of an unruptured intracranial aneurysm (UIA). This study aimed to compare the effects of fluid regimens between NS and BC on the metabolic and clinical outcomes of patients who underwent surgery for UIA. Methods: : This study was designed as a propensity score matched retrospective comparative study and included adult patients who underwent UIA clipping. Patient groups were categorized as NS and BC groups based on the types of pre-operative fluid and the amount of fluid administered during surgery. The primary outcomes were defined as electrolyte imbalance and acidosis immediately after surgery. The secondary outcomes were the length of stay in the intensive care unit (ICU) and duration from the end of the operation to extubation. Results: : A total of 586 patients were enrolled in this study, with each of 293 patients assigned to the NS and BC groups, respectively. Immediately after surgery, serum chloride levels were significantly higher in the NS group. Compared to the NS group, the BC group had lower incidence rates of acidemia (6.5% vs. 11.6%, p=0.043) and metabolic acidosis (0.7% vs. 4.4%, p=0.007). As compared to NS group, BC group had significantly shorter duration from the end of the operation to extubation (250±824 vs. 122±372 minutes, p=0.016) and length of stay in ICU (1.37±1.11 vs. 1.12±0.61 days, p=0.001). Throughout multivariable analysis, use of BC was found to be significant factor for favorable post-operative results. Conclusion : This study showed that the patients who received BC during UIA clipping had lower incidence of metabolic acidosis, earlier extubation and shorter ICU stay compared to those who received NS. Therefore, using BC as a peri-operative fluid can be recommended for patients who undergo surgery for UIA.