Survival pattern of metastatic renal cell carcinoma patients according to WHO/ISUP grade: a long-term multi-institutional study.

The World Health Organization/International Society of Urological Pathology (WHO/ISUP) grading of renal cell carcinoma (RCC) is classified from grade 1-4, regardless of subtype. The National Comprehensive Cancer Network (NCCN) guidelines (2022) state that if there is an adverse pathological feature, such as grade 3 or higher RCC in stage 1 patients, more rigorous follow-up imaging is recommended. However, the RCC guidelines do not provide specific treatment or follow-up policies by tumor grade. Therefore, this study attempted to find out whether tumor grade affects survival rates in patients with metastatic RCC. The Korean Renal Cancer Study Group (KRoCS) database includes 3108 patients diagnosed with metastatic RCC between September 1992 and February 2017, with treatment methods, progression, and survival data collected from 11 tertiary hospitals. To obtain information on survival rates or causes of death, we utilized the Korea National Statistical Office database and institutional medical records. Data were accessed for research purpose on June, 2023. We then reviewed these sources to gather comprehensive and reliable data on the outcomes of our study cohort. This database was retrospectively analyzed, and out of 3108 metastatic RCC patients, 911 had been identified as WHO/ISUP grade. Grades were classified into either a low-grade (WHO/ISUP grade 1-2) or a high-grade group (WHO/ISUP grade 3-4). The patients were then analyzed related to progression and overall survival (OS). In metastatic clear cell RCC patients, the 1-year OS rate was 69.4% and the median OS was 17.0 months (15.5-18.5) followed up to 203.6 months. When comparing the patient groups, 119 low-grade and 873 high-grade cases were identified. No baseline difference was observed between the two groups, except that the high-grade group had a higher ECOG 1 ratio of 50.4% compared with 34.5% for the low-grade group (p = 0.009). There was a significant difference in OS between high-grade and low-grade groups. OS was 16.0 months (14.6-17.4) in the high-grade group and 28.0 months (21.1-34.9) in the low-grade group (p < 0.001). However, there was no difference in progression-free survival (PFS) rates with 9.0 months (8.0-10.0) for the high-grade group and 10.0 months (6.8-13.2) for the low-grade group (p = 0.377) in first-line treatment. In multivariable analysis, WHO/ISUP grade was a risk factor (HR = 1.511[1.135-2.013], p = 0.005) that influenced the OS. In conclusion, WHO/ISUP grade is a major data source that can be used as a ubiquitous marker of metastatic RCC in pre-IO era. Depending on whether the RCC is high or low grade, the follow-up schedule will need to be tailored according to grade, with higher-grade patients needing more active treatment as it can not only affect the OS in the previously known localized/locoregional recurrence but also the metastatic RCC patient.

Epidemiology of mumps, mumps complications, and mumps orchitis in Korea using the National Health Insurance Service database.

PURPOSE: To analyze the presentation of mumps and mumps orchitis using the National Health Insurance Service Database (NHISD). MATERIALS AND METHODS: Using information from the NHISD representing all cases of mumps in Korea, data regarding mumps orchitis were analyzed. The International Classification of Diseases, Tenth Revision, and Clinical Modification codes were used for diagnosis. The incidence estimates of the number of mumps cases were analyzed using the Statistical Analysis System (SAS) software. RESULTS: Based on the NHISD, 199,186 people were diagnosed with mumps, and males accounted for 62.3% cases. Teen males accounted for 69,870 cases, the largest number of patients diagnosed with mumps. The annual incidence of mumps increased every year (poisson regression, hazard ratio [HR] 1.026, 95% confidence interval [CI] 1.024-1.027; p<0.025). The risk of mumps was lower in females than that in males (poisson regression, HR 0.594, 95% CI 0.589-0.599; p<0.001). Of the 199,186 patients diagnosed with mumps, 3,872 patients (1.9%) had related complications. Among the mumps complications, the most diagnosed complication was mumps orchitis, which was seen in 41.8% of the males. Mumps orchitis cases accounted for less than 1.5% of the patients with mumps in minors under the age of 20 years and was somewhat higher in 2009 and 2013-2015. CONCLUSIONS: Among the complications related to mumps, meningitis was most common in females, while orchitis was dominant in males. Mumps orchitis also shows periodic outbreaks but is particularly prevalent in adults, which suggests the potential need for additional vaccination against mumps.

Cinnamomum verum extract inhibits NOX2/ROS and PKCδ/JNK/AP-1/NF-κB pathway-mediated inflammatory response in PMA-stimulated THP-1 monocytes.

BACKGROUND: Cinnamomum verum J. Presl (Cinnamon) is widely used in the food and pharmaceutical industries. C. verum exhibits various biological activities. However, it is unclear whether C. verum can inhibit NOX, a major source of ROS generation, and exert anti-inflammatory and antioxidant effects in PMA-stimulated THP-1 cells. PURPOSE: This study investigates the anti-inflammatory and antioxidant effects of C. verum in PMA-stimulated THP-1 cells. METHODS: The MeOH extract of C. verum was analyzed using UPLC-QTOF/MS. Anti-inflammatory and antioxidant effects of C. verum extract were examined by DCF-DA staining, immunofluorescence staining, RT-PCR, and immunoblotting in PMA-stimulated THP-1 cells. RESULTS: C. verum and its components, cinnamic acid and coumarin, significantly attenuated the expression of IL-1ß, IL-8, CCL5, and COX-2 in PMA-stimulated THP-1. C. verum decreased ROS levels via NOX2 downregulation, as well as ameliorated plasma membrane translocation of PKCδ and decreased JNK phosphorylation. Besides, C. verum suppressed the nuclear translocation of AP-1 and NF-κB, which modulates diverse pro-inflammatory genes. CONCLUSION: C. verum effectively inhibits inflammation and oxidative stress during monocyte-macrophage differentiation and downregulates inflammatory mediators via NOX2/ROS and PKCδ/JNK/AP-1/NF-κB signaling.

α-Blocker and Risk of Dementia in Patients with Benign Prostatic Hyperplasia: A Nationwide Population Based Study Using the National Health Insurance Service Database.

PURPOSE: A recent study demonstrated that tamsulosin increased the risk of dementia in patients with benign prostatic hyperplasia. However, this study had a number of limitations. We evaluated the association between α-blockers and dementia in patients with benign prostatic hyperplasia. MATERIALS AND METHODS: From the National Health Insurance Service database we collected and analyzed data on α-blockers and dementia in the entire Korean adult population with benign prostatic hyperplasia between January 2011 and December 2011. These patients were followed until September 2017. We tested the effect of α-blockers on the risk of dementia using propensity score matched Cox proportional hazard regression models and Kaplan-Meier survival analysis. RESULTS: During a mean ± SD followup of 1,580 ± 674.3 days all study inclusion and exclusion criteria were met by 59,263 patients with benign prostatic hyperplasia. In the unadjusted cohort the incidence of dementia in the tamsulosin, doxazosin, terazosin, alfuzosin and no medication cohorts were 17.97%, 18.55%, 20.64%, 17.62% and 22.60%, respectively. After propensity score matching the risk of dementia did not significantly differ in the tamsulosin cohort vs the doxazosin and alfuzosin cohorts (HR 1.038, 95% CI 0.960-1.121 and HR 1.008, 95% CI 0.925-1.098), respectively. Compared to the tamsulosin cohort the terazosin cohort had a higher risk of dementia (HR 1.112, 95% CI 1.052-1.196). However, the risk of dementia was significantly lower in the terazosin cohort than in the no medication cohort. CONCLUSIONS: The study findings indicate that benign prostatic hyperplasia medication is not associated with a risk of dementia by duration of use or by type.

Correlation of Androgen Deprivation Therapy with Cognitive Dysfunction in Patients with Prostate Cancer: A Nationwide Population-Based Study Using the National Health Insurance Service Database.

PURPOSE: The purpose of this study was to evaluate the association of androgen deprivation therapy (ADT) with cognitive dysfunction. MATERIALS AND METHODS: Using the National Health Insurance Service database of the entire Korean adult prostate cancer population (n=236,391), data on ADT and cognitive dysfunction between 2008 and 2015 were analyzed. We excluded patients previously diagnosed with cognitive dysfunction, dementia, or a cerebral event history. We tested the effect of ADT on the risk of cognitive dysfunction using propensity score-matched Cox proportional hazards regression models and Kaplan-Meier survival analysis. Our final cohort comprised of 35,401 individuals with prostate cancer, including 24,567 men (70.6%) who underwent ADT. RESULTS: During a mean follow-up period of 4.1 years, 4,741 patients were newly diagnosed with cognitive dysfunction. A statistically significant association was found between ADT and the risk of cognitive dysfunction (hazard ratio, 1.169; p=0.002). Meanwhile, age (≥ 70 years), diabetes, hypertension, cardiovascular history, and peripheral vascular disease were identified as factors that contribute to the increased risk of cognitive dysfunction. In contrast, the use of statins and aspirin was associated with a lower risk of cognitive dysfunction. Kaplan-Meier analysis demonstrated that patients aged 70 years or older who underwent ADT had the lowest cumulative probability of remaining cognitive dysfunction-free (log-rank p < 0.001). CONCLUSION: Our. RESULTS: revealed an association between the use of ADT for the treatment of prostate cancer and an increased risk of cognitive dysfunction in a nationwide population-based study. This finding should be further evaluated in prospective studies.

Effects of lifetime cumulative ginseng intake on cognitive function in late life.

BACKGROUND: We investigated the effects of lifetime cumulative ginseng intake on cognitive function in a community-dwelling population-based prospective cohort of Korean elders. METHODS: Community-dwelling elders (N = 6422; mean age = 70.2 ± 6.9 years, education = 8.0 ± 5.3 years, female = 56.8%) from the Korean Longitudinal Study on Cognitive Aging and Dementia were included. Among them, 3918 participants (61.0%) completed the 2-year and 4-year follow-up evaluations. Subjects were categorized according to cumulative ginseng intake at baseline evaluation; no use group, low use (< 5 years) group, and high use (≥ 5 years) group. One-way analysis of covariance (ANCOVA) was conducted to compare the impact of cumulative ginseng intake on baseline Consortium to Establish a Registry for Alzheimer's Disease Assessment Packet neuropsychological battery total score (CERAD total score) and Mini-Mental State Examination (MMSE) score among the three groups while adjusting for potential covariates. A repeated-measures ANCOVA was performed to investigate the impacts on the changes in CERAD total scores and MMSE scores during the 4 years of follow-up. RESULTS: The high use group showed higher CERAD total scores compared to the no use group after controlling for age, sex, education years, socioeconomic status, smoking, alcohol intake, presence of hypertension, stroke history, Geriatric Depression Scale, Cumulative Illness Rating Scale, and presence of the APOE e4 allele (F(2, 4762) = 3.978, p = 0.019). The changes of CERAD total score for 2 or 4 years of follow-up did not differ according to the use of ginseng. CONCLUSIONS: Cumulative ginseng use for longer than 5 years may be beneficial to cognitive function in late life.

Prediction of persistent storage symptoms after transurethral resection of the prostate in patients with benign prostatic enlargement.

OBJECTIVE: To identify the prognostic factors causing persistent storage symptoms following transurethral resection of the prostate in patients with benign prostatic enlargement (BPE). METHODS: A total of 116 men with symptomatic BPE requiring surgery were enrolled in the study between January 2011 and December 2012. The patients underwent basic clinical evaluations including transrectal ultrasound, International Prostate Symptom Score and urodynamic study. After 6 months, International Prostate Symptom Score and uroflowmetry were rechecked. The definition of persistent storage symptoms was patients with storage scores >7 points. Logistic regression analysis and receiver operating characteristic analysis were conducted. RESULTS: The 116 patients were divided into a persistent storage symptom-positive group (n = 33) and a storage symptom-negative group (n = 83). Multivariate analysis showed that the degrees of worse initial storage symptoms (odds ratio [OR] = 8.32), small bladder capacity (OR = 4.31), impaired detrusor contractility (OR = 2.96) and age (OR = 1.05) were consistently associated with persistent storage symptoms. CONCLUSIONS: This short-term study confirms the positive and consistent correlations between the baseline degree of worse initial storage symptoms, bladder capacity, detrusor contractility and age and the improvement in storage symptoms.

Anti-obesity effects of Lysimachia foenum-graecum characterized by decreased adipogenesis and regulated lipid metabolism.

Lysimachia foenum-graecum has been used as an oriental medicine with anti-inflammatory effect. The anti-obesity effect of L. foenum-graecum extract (LFE) was first discovered in our screening of natural product extract library against adipogenesis. To characterize its anti-obesity effects and to evaluate its potential as an anti-obesity drug, we performed various obesity-related experiments in vitro and in vivo. In adipogenesis assay, LFE blocked the differentiation of 3T3-L1 preadipocyte in a dose-dependent manner with an IC50 of 2.5 µg/ml. In addition, LFE suppressed the expression of lipogenic genes, while increasing the expression of lipolytic genes in vitro at 10 µg/ml and in vivo at 100 mg/kg/day. The anti-adipogenic and anti-lipogenic effect of LFE seems to be mediated by the inhibition of PPARγ and C/EBPα expression as shown in in vitro and in vivo, and the suppression of PPARγ activity in vitro. Moreover, LFE stimulated fatty acid oxidation in an AMPK-dependent manner. In high-fat diet (HFD)-induced obese mice (n = 8/group), oral administration of LFE at 30, 100, and 300 mg/kg/day decreased total body weight gain significantly in all doses tested. No difference in food intake was observed between vehicle- and LFE-treated HFD mice. The weight of white adipose tissues including abdominal subcutaneous, epididymal, and perirenal adipose tissue was reduced markedly in LFE-treated HFD mice in a dose-dependent manner. Treatment of LFE also greatly improved serum levels of obesity-related biomarkers such as glucose, triglycerides, and adipocytokines leptin, adiponectin, and resistin. All together, these results showed anti-obesity effects of LFE on adipogenesis and lipid metabolism in vitro and in vivo and raised a possibility of developing LFE as anti-obesity therapeutics.