Efficacy and safety of dapagliflozin in children with kidney disease: real-world data.

BACKGROUND: Dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, has shown results in slowing estimated glomerular filtration rate (eGFR) decline and reducing proteinuria in adult patients with chronic kidney disease. This retrospective study examines dapagliflozin's effects in 22 children with kidney disease and proteinuria. METHODS: Children with a median age of 15.6 years were treated with dapagliflozin for > 3 months between July 2022 and December 2023. All children had been treated with either an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker for at least 1 month before starting dapagliflozin. RESULTS: The most common kidney disease diagnoses in this study included Alport syndrome (n = 7) and medication-resistant nephrotic syndrome or focal segmental glomerulosclerosis (n = 7). After 6.1 months of treatment, dapagliflozin treatment did not result in significant changes in eGFR or proteinuria. However, at the latest follow-up, a statistically significant decrease in eGFR was noted (65.5 compared to the baseline 71.1 mL/min/1.73 m2, P = 0.003). Proteinuria remained stable between baseline and the last follow-up (final spot urine protein/creatinine ratio (uPCR) 0.7 vs. baseline uPCR 0.6 mg/mg, P = 0.489). In the subgroup analysis of children treated for > 8 months, the eGFR decline post-treatment changed from - 0.5 to - 0.2 ml/min/1.73 m2 per month (P = 0.634). Only two children discontinued dapagliflozin due to suspected adverse events. CONCLUSIONS: Dapagliflozin has not been associated with serious side effects. Further prospective clinical trials are needed to confirm the efficacy and safety of dapagliflozin in children with kidney disease.

The pathologic and clinical outcomes of risk-reducing salpingo-oophorectomy in asymptomatic carriers of homologous recombination repair gene mutation.

OBJECTIVE: To investigate the prevalence of pathological findings and clinical outcomes of risk-reducing salpingo-oophorectomy (RRSO) in asymptomatic carriers with germline homologous recombination repair (HRR) gene pathogenic/likely pathogenic variants (PV/LPV). METHODS: This retrospective study enrolled asymptomatic carriers with germline HR gene PV/LPV who underwent RRSO between 2006 and 2022 at the National Cancer Center in Korea. Clinical characteristics, including history of breast cancer, family history of ovarian/breast cancer, parity, and oral contraceptive use, were analyzed. RESULTS: Of the 255 women who underwent RRSO, 129 (50.6%) had PV/LPV in BRCA1, 121 (47.5%) in BRCA2, and 2 (0.7%) had both BRCA1 and BRCA2 PV/LPV. In addition, 1 carried PV/LPV in RAD51D, and 2 in BRIP1. Among the BRCA1/2 PV/LPV carriers, occult neoplasms were identified in 3.5% of patients: serous tubal intraepithelial carcinoma (1.1%, n=3), fallopian tubal cancers (0.8%, n=2), ovarian cancer (1.2%, n=3), and breast cancer (0.4%, n=1). Of the 9 patients with occult neoplasms, 5 (2.0%) were identified from the 178 breast cancer patients, and 4 (1.6%) were detected in 65 healthy mutation carriers. During the median follow-up period of 36.7 months (interquartile range, 25.9-71.4), 1 (0.4%) BRCA1 PV carrier with no precursor lesions at RRSO developed primary peritoneal carcinomatosis after 30.1 months. CONCLUSION: Women with HRR gene mutations PV/LPV who undergo RRSO are at a risk of detecting occult neoplasms, with a of 3.5%. Even in the absence of precursor lesions during RRSO, there was a cumulative risk of peritoneal carcinomatosis development, emphasizing the need for continued surveillance.

Gastric and colorectal cancer incidence attributable to dietary factors in Korea.

Background: Dietary factors play a role in the etiology of gastrointestinal cancer. We aimed to estimate the burden of gastric and colorectal cancer that can be attributable to dietary factors in adults aged 20 years and older in Korea in 2018. Methods: Dietary intakes in 2000 were estimated using data from the 2001, 2005, and 2007-2018 Korea National Health and Nutrition Examination Survey (KNHANES). For counterfactual scenarios, the optimal level of intake suggested by the Global Burden of Disease (GBD) study was used if it was available. Otherwise, the average intake values of reference groups among published studies globally were used. Relative risks (RRs) were pooled through dose-response meta-analyses of Korean studies. Results: In Korea in 2018, an estimated 18.6% of gastric cancer cases and 34.9% of colorectal cancer cases were attributed to the combined effect of evaluated dietary factors. High intake of salted vegetables accounted for 16.0% of gastric cancer cases, followed by salted fish at 2.4%. Low intakes of whole grains (16.6%) and milk (13.7%) were leading contributors to colorectal cancer cases, followed by high intakes of processed meat (3.1%) and red meat (5.9%), and a low intake of dietary fiber (0.5%). Conclusions: These results suggest that a considerable proportion of gastric and colorectal cancer incidence might be preventable by healthy dietary habits in Korea. However, further research is needed to confirm the associations between dietary factors and gastric and colorectal cancers in Korea and to formulate and apply effective cancer prevention strategies to Koreans.

Prognostic Role of CA-125 Elimination Rate Constant (KELIM) in Patients with Advanced Epithelial Ovarian Cancer Who Received PARP Inhibitors.

BACKGROUND: This multicenter retrospective study aimed to investigate the prognostic value of the CA-125 elimination rate constant K (KELIM) in EOC patients who received platinum-based chemotherapy followed by PARP inhibitors, in either upfront or interval treatment settings. METHODS: Between July 2019 and November 2022, we identified stage III-IV EOC patients who underwent primary or interval cytoreductive surgery and received olaparib or niraparib. Individual KELIM values were assessed based on validated kinetics and classified into favorable and unfavorable cohorts. RESULTS: In a study of 252 patients undergoing frontline maintenance therapy with olaparib or niraparib, favorable KELIM (≥1) scores were associated with a higher PFS benefit in the primary cytoreductive surgery (PCS) cohort (hazard ratio (HR) for disease progression or death 3.51, 95% confidence interval (CI); 1.37-8.97, p = 0.009). Additionally, within the interval cytoreductive surgery (ICS) cohort, a favorable KELIM score (≥1) significantly increased the likelihood of achieving complete resection following cytoreductive surgery, with 59.4% in the favorable KELIM group compared to 37.8% in those with unfavorable KELIM. CONCLUSIONS: A favorable KELIM score was associated with improved PFS in patients with advanced EOC undergoing PCS. Furthermore, in the ICS cohort, a favorable KELIM score increased the probability of complete cytoreduction.

Deep Learning-Based Dynamic Risk Prediction of Venous Thromboembolism for Patients With Ovarian Cancer in Real-World Settings From Electronic Health Records.

PURPOSE: Patients with epithelial ovarian cancer (EOC) have an elevated risk for venous thromboembolism (VTE). To assess the risk of VTE, models were developed by statistical or machine learning algorithms. However, few models have accommodated deep learning (DL) algorithms in realistic clinical settings. We aimed to develop a predictive DL model, exploiting rich information from electronic health records (EHRs), including dynamic clinical features and the presence of competing risks. METHODS: We extracted EHRs of 1,268 patients diagnosed with EOC from January 2007 through December 2017 at the National Cancer Center, Korea. DL survival networks using fully connected layers, temporal attention, and recurrent neural networks were adopted and compared with multi-perceptron-based classification models. Prediction accuracy was independently validated in the data set of 423 patients newly diagnosed with EOC from January 2018 to December 2019. Personalized risk plots displaying the individual interval risk were developed. RESULTS: DL-based survival networks achieved a superior area under the receiver operating characteristic curve (AUROC) between 0.95 and 0.98 while the AUROC of classification models was between 0.85 and 0.90. As clinical information benefits the prediction accuracy, the proposed dynamic survival network outperformed other survival networks for the test and validation data set with the highest time-dependent concordance index (0.974, 0.975) and lowest Brier score (0.051, 0.049) at 6 months after a cancer diagnosis. Our visualization showed that the interval risk fluctuating along with the changes in longitudinal clinical features. CONCLUSION: Adaption of dynamic patient clinical features and accounting for competing risks from EHRs into the DL algorithms demonstrated VTE risk prediction with high accuracy. Our results show that this novel dynamic survival network can provide personalized risk prediction with the potential to assist risk-based clinical intervention to prevent VTE among patients with EOC.

Efficacy of immune-checkpoint inhibitors combined with cytotoxic chemotherapy in advanced or recurrent endometrial cancer: A systematic review and meta-analysis.

BACKGROUND: The combination of immune checkpoint inhibitors (ICIs) and platinum-based chemotherapy has emerged as a highly promising primary option for advanced or recurrent endometrial cancer (EC). The study aimed to evaluate treatment efficacy of ICIs with cytotoxic chemotherapy in EC. METHODS: We conducted a comprehensive review of randomized controlled trials up to November 11, 2023, focusing on immunotherapy combined with chemotherapy versus chemotherapy alone for EC. The primary endpoint was the pooled hazard ratio (HR), which was further analyzed across subgroups based on mismatch repair (MMR) status, race, histology, and programmed death-ligand 1 (PD-L1) status. The protocol was registered in PROSPERO (CRD42023475669). FINDINGS: Four trials with 2335 patients were analyzed. ICIs with chemotherapy significantly prolonged progression-free survival (PFS) (HR, 0.70; 95% CI, 0.62-0.79) and overall survival (OS) (HR, 0.75; 95% CI, 0.63-0.89) compared to chemotherapy alone. Stratification by MMR status showed substantial benefits for dMMR (PFS; HR, 0.33; 95% CI, 0.26-0.43; OS; HR, 0.37; 95% CI, 0.22-0.91) over pMMR cohorts in both PFS and OS. In the subgroup analysis, there was significant PFS advantage in Caucasian (HR, 0.63; 95% CI, 0.54-0.72) over non-Caucasian, in endometrioid histology (HR, 0.66; 95% CI, 0.56-0.78) over non-endometrioid, and in PD-L1 positive (HR, 0.39; 95% CI, 0.19-0.81) over PD-L1 negative population. INTERPRETATION: ICIs combined with platinum-based chemotherapy significantly prolonged PFS and OS in patients with advanced or recurrent EC. Patients with dMMR status, Caucasians, endometrioid histology, and positive PD-L1 status showed significant PFS benefits, emphasizing the need for personalized treatment approaches to improve outcomes.

Dietary mercury intake, the IL23R rs10889677 polymorphism, and the risk of gastric cancer: a hospital-based case-control study.

Objectives: Mercury can stimulate immune responses through T helper 17 (Th17). The gene IL23R is a key factor in Th17 function, which may also contribute to digestive tract diseases. The aim of this study was to observe the associations between dietary mercury and gastric cancer (GC) and to investigate whether the IL23R rs10889677 polymorphism modifies those associations. Methods: This case-control study included 377 patients with GC and 756 healthy controls. Dietary mercury intake (total mercury and methylmercury) was assessed using a dietary heavy metal database incorporated into the food frequency questionnaire. IL23R genetic polymorphism rs10889677 (A>C) was genotyped. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using unconditional logistic regression models with adjustments for potential confounders. Results: A higher dietary methylmercury intake was associated with an elevated risk of GC (OR for the highest versus lowest tertile [T3 vs. T1]=2.02; 95% CI, 1.41-2.91; p for trend <0.001). The IL23R rs10889677 reduced the risk of GC in individuals who carried at least 1 minor allele (OR=0.62; 95% CI, 0.46-0.83; p=0.001; AC/CC vs. AA). Individuals with a C allele exhibited a lower susceptibility to GC through methylmercury intake than those with the AA genotype (OR for the T3 of methylmercury and AA carriers=2.93; 95% CI, 1.77-4.87; and OR for the T3 of methylmercury and AC/CC genotype=1.30; 95% CI, 0.76-2.21; p-interaction=0.013). Conclusion: Our findings suggest that a genetic polymorphism, rs10889677 in IL23R, plays a role in modifying the association between dietary methylmercury intake and the risk of GC.

Anti-Inflammatory Effects of Artemisia argyi H. Fermented by Lactobacillus plantarum in the LPS-Induced RAW 264.7 Cells and DSS-Induced Colitis Model.

Ulcerative colitis is a chronic inflammatory disease caused by abnormal immune responses in the intestinal mucosa and gut microorganisms. Unlike other mugworts, Artemisia argyi H. (A. argyi H.) enhances antioxidant, anti-inflammatory, and anticancer effects, but the improvement effects against gut inflammation have not yet been reported. Therefore, this study aimed to confirm the alleviation of the inflammatory state in the gut by A. argyi H. fermented with Lactobacillus plantarum (FAA), using lipopolysaccharide (LPS)-induced RAW 264.7 cells and dextran sulfate sodium (DSS)-induced colitis models. In vitro, FAA (10, 50, 100, and 200 µg/mL) was pretreated into RAW 264.7 cells, followed with LPS (100 ng/mL), which induced the cell damage. Meanwhile, in vivo, FAA (100, 200 mg/kg/day) was orally administered into 6-week-old C57BL/6N mice for 3 weeks. During the last week of FAA administration, 2.5% DSS was used to induce colitis. The results showed that FAA reduced the production of nitric oxide (p < 0.0001), tumor necrosis factor (TNF)-α, interleukin (IL)-6 (p < 0.0001), and IL-1ß (p < 0.0001) in the LPS-induced RAW 264.7 cells. Moreover, in the DSS-induced colitis model, FAA alleviated clinical symptoms (p < 0.001), inhibited the inflammatory state by reducing the production of TNF-α (p < 0.0001) and interferon-γ in intestinal immune cells (p < 0.0001), and strengthened the intestinal barrier by increasing the number of goblet cells (p < 0.0001). Furthermore, the anti-inflammatory effects were confirmed by the alleviation of histological damage (p < 0.001) and down-regulation of the expression of inflammatory proteins (TLR4, p < 0.0001; MyD88, p < 0.0001; Cox-2, p < 0.0001). These results suggest the potential of FAA as a dietary ingredient for preventing inflammation in the gut.

Association between Atherosclerosis and High-Risk Colorectal Adenomas based on Cardio-Ankle Vascular Index and Ankle-Brachial Index.

Background/Aims: Colorectal adenomas are precancerous lesions that may lead to colorectal cancer. Recent studies have shown that colorectal adenomas are associated with atherosclerosis. The cardio-ankle vascular index (CAVI) and ankle-brachial index (ABI) are noninvasive methods for evaluating atherosclerosis. This study examined the association between atherosclerosis and high-risk colorectal adenomas based on the CAVI and ABI. Methods: The data of patients aged ≥50 years who had a colonoscopy and CAVI and ABI measurements from August 2015 to December 2021 at the Kangwon National University Hospital were analyzed retrospectively. After the colonoscopy, subjects were divided into no, overall, and high-risk (size ≥1 cm, high-grade dysplasia or villous adenoma, three or more adenomas) adenoma groups based on the pathology findings. The data were subjected to univariate and multivariate logistic regression analyses. Results: Among the 1,164 subjects, adenomas and high-risk adenomas were found in 613 (52.6%) and 118 (10.1%) patients, respectively. The rate of positive ABI (<0.9) and positive CAVI (≥9.0) were significantly higher in the high-risk adenoma group (22.0% and 55.9%) than in the no adenoma (12.3% and 39.6%) and the overall adenoma group (15.7% and 44.0%) (p=0.008 and p=0.006, respectively). Multivariate analysis revealed a positive CAVI and smoking status to be significantly associated with high-risk adenoma with an odds ratio of 1.595 (95% confidence interval 1.055-2.410, p=0.027) and 1.579 (1.072-2.324, p=0.021), respectively. Conclusions: In this study, a significant correlation between positive CAVI and high-risk adenomas was observed. Therefore, CAVI may be a significant predictor for high-risk colorectal adenoma.

Co-treatment with the seed of Carthamus tinctorius L. and the aerial part of Taraxacum coreanum synergistically suppresses Aß25-35-induced neurotoxicity by altering APP processing.

Accumulation of ß-amyloid peptide (Aß) induces neurotoxicity, which is the primary risk factor in the pathogenesis of Alzheimer's disease (AD). The cleavage of amyloid precursor protein (APP) by the ß- (BACE) and γ- (PS1, PS2) secretases is a critical step in the amyloidogenic pathway. The induction of neuronal apoptosis by Aß involves increased expression of B-cell lymphoma protein 2 (Bcl-2)-associated X (Bax) and decreased Bcl-2 expression. The seed of Carthamus tinctorius L. (CTS) and the aerial part of Taraxacum coreanum (TC) are traditional herbs used to treat several neurodegenerative diseases. In this study, the neuroprotective effects of co-treatment with CTS and TC on Aß-induced neurotoxicity in SH-SY5Y neuroblastoma cells and the underlying mechanisms were investigated. CTS, TC, and the co-treatment (CTS + TC) were added to Aß25-35-treated SH-SY5Y cells. CTS + TC synergistically increased cell viability and inhibited reactive oxygen species production. CTS + TC resulted in significant downregulation of BACE, PS1, PS2, and APP, as well as the 99-aa C-terminal domain of APP, compared with either CTS or TC alone. Compared with the single herbs, co-treatment with CTS and TC markedly decreased the expression of Bax and increased the expression of Bcl-2, consistent with its anti-apoptotic effects. These findings suggest that co-treatment with CTS and TC may be useful for AD prevention.

Association between short-term exposure to ambient air pollutants and biomarkers indicative of inflammation and oxidative stress: a cross-sectional study using KoGES-HEXA data.

BACKGROUND: Air pollution-induced systemic inflammation and oxidative stress are hypothesized to be the major biological mechanisms underlying pathological outcomes. We examined the association between short-term exposure to ambient air pollutants and biomarkers of inflammation and oxidative stress in 2199 general middle-aged Korean population residing in metropolitan areas. METHODS: Serum levels of inflammatory cytokines (interleukin [IL]-1ß, IL-6, IL-8, IL-10, and tumor necrosis factor [TNF]-α) and urinary levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) were measured. Daily concentrations of a series of air pollutants (particulate matter [PM]10, PM2.5, SO2, NO2, CO, and O3) were predicted using the Community Multiscale Air Quality modeling system, and participant-level pollutant exposure was determined using geocoded residential addresses. Short-term exposure was defined as the 1- to 7-day moving averages. RESULTS: The multivariable-adjusted linear models controlling for the sociodemographic, lifestyle, temporal, and meteorological factors identified positive associations of PM with IL-1ß, IL-8, IL-10, TNF-α, and 8-OHdG levels; SO2 with IL-10 levels, CO with IL-1ß, IL-10, and TNF-α levels; and O3 with IL-1ß, IL-8, and 8-OHdG levels. O3 levels were inversely associated with IL-10 levels. For each pollutant, the strongest associations were observed for the 7-day average PM and CO with IL-1ß (per 10-µg/m3 increase in PM10: 2.7%, 95% confidence interval [CI] = 0.6-4.8; per 10-µg/m3 increase in PM2.5: 6.4%, 95% CI = 2.4-10.5; per 0.1-ppm increase in CO: 3.3%, 95% CI = 0.3-6.5); the 2-day average SO2 with IL-10 levels (per 1-ppb increase in SO2: 1.1%, 95% CI = 0.1-2.1); and the 7-day average O3 with IL-8 levels (per 1-ppb increase in O3: 1.3%, 95% CI = 0.7-1.9). CONCLUSIONS: Short-term exposure to ambient air pollutants may induce oxidative damage and pro-inflammatory roles, together with counter-regulatory anti-inflammatory response.

Development of an Automatic Rule-Based Algorithm for the Detection of Ovarian Cancer Recurrence From Electronic Health Records.

PURPOSE: As the onset of cancer recurrence is not explicitly recorded in the electronic health record (EHR), a high volume of manual chart review is required to detect the cancer recurrence. This study aims to develop an automatic rule-based algorithm for detecting ovarian cancer (OC) recurrence on the basis of minimally preprocessed EHR data. METHODS: The automatic rule-based recurrence detection algorithm (Auto-Recur), using notes on image reading (positron emission tomography-computed tomography [PET-CT], CT, magnetic resonance imaging [MRI]), biomarker (CA125), and treatment information (surgery, chemotherapy, radiotherapy), was developed to detect the first OC recurrence. Auto-Recur contains three single algorithms (images, biomarkers, treatments) and hybrid algorithms (combinations of the single algorithms). The performance of Auto-Recur was assessed using sensitivity, specificity, and accuracy of the recurrence time detected. The recurrence-free survival probabilities were estimated and compared with the retrospective chart review results. RESULTS: The proposed Auto-Recur considerably reduced human resources and time; it saved approximately 1,340 days when scaled to 100,000 patients compared with the conventional retrospective chart review. The hybrid algorithm on the basis of a combination of image, biomarker, and treatment information was the most efficient (sensitivity: 93.4%, specificity: 97.4%) and precisely captured recurrence time (average time error: 8.5 days). The estimated 3-year recurrence-free survival probability (44%) was close to the estimates by the retrospective chart review (45%, log-rank P value = .894). CONCLUSION: Our rule-based algorithm effectively captured the first OC recurrence from large-scale EHR while closely approximating the recurrence-free survival estimates obtained by conventional retrospective chart reviews. The study findings facilitate large-scale EHR analysis, enhancing clinical research opportunities.

Prospective analysis of pre and postoperative laboratory parameters associated with thrombosis in patients with ovarian cancer.

Patients with ovarian cancer have a high risk of developing thrombosis. We aimed to investigate pre and post operative biomarkers associated with thrombosis including deep vein thrombosis and pulmonary thromboembolism in patients treated for ovarian cancer. We collected pre and post operative blood samples from 133 patients undergoing surgery for ovarian cancer between December 2021 and August 2022. The measured parameters were white blood cell count, hemoglobin, platelets, monocytes, serum glucose, CA125, D-dimer, fibrinogen, prothrombin time, activated partial thromboplastin time, fibrinogen degradation products, antithrombin III, protein C, protein S, plasminogen, plasminogen activator inhibitor 1, homocysteine, N-terminal pro-brain natriuretic peptide, interleukin 6, thrombopoietin, soluble P-selectin and granulocyte stimulating factor. Body mass index of patients were collected. Differences between patients who developed thrombosis and those without were compared with Wilcoxon rank-sum test and we analyzed the continuous variables using logistic regression. Twenty-one (15.8%) patients developed thrombosis ranging from 6 to 146 days (median 15 days) after surgery. Pre operative values of homocysteine (p = 0.033) and IL-6 (p = 0.043) were significantly increased and post operative aPTT (p = 0.022) was prolonged and plasminogen (p = 0.041) was decreased in patients with thrombosis. It is important to find novel biomarkers for thrombosis to carefully manage patients who are prone to develop thrombosis despite preventive measures were applied.

Preoperative laboratory parameters associated with deep vein thrombosis in patients with ovarian cancer: retrospective analysis of 3,147 patients in a single institute.

OBJECTIVE: Patients with ovarian cancer have a high risk of developing thrombosis. We aimed to investigate laboratory parameters associated with deep vein thrombosis (DVT) in patients treated for ovarian cancer. METHODS: We retrospectively analyzed pre-operation laboratory data of patients with ovarian cancer for DVT at the National Cancer Center, Korea, between January 2000 and February 2021. The test items were white blood cell count, absolute neutrophil count (ANC), hemoglobin, platelets, monocytes, serum glucose, CA125, D-dimer, fibrinogen, prothrombin time (PT), activated partial thromboplastin time (aPTT), and body mass index (BMI). Differences between patients with and without DVT were compared with Wilcoxon rank-sum test. We analyzed the variables using logistic regression. Items with significant odds ratios were included in multivariate logistic regression. Significant variables were selected using backward elimination. Items were further categorized based on reference ranges. Univariate and multivariate analyses were performed to identify items with abnormal values associated with DVT. RESULTS: From 3,147 patient samples analyzed, 286 (9.1%) patients with DVT were selected. Differences between patients with vs without DVT were statistically significant for hemoglobin, monocyte, serum glucose, CA125, PT, aPTT, fibrinogen, D-dimer, and BMI. After univariate and multivariate analysis, monocyte, glucose, and PT remained significant. Among the categorical variables, low hemoglobin, high monocyte, high CA125, prolonged PT, and high BMI remained significant after univariate and multivariate analysis. CONCLUSION: Pre-operation laboratory data of low hemoglobin, high monocyte percentage, high serum glucose, high CA125, prolonged PT, and high BMI were associated with DVT.

Sex-dependent different clinicopathological characterization of Epstein-Barr virus-associated gastric carcinoma: a large-scale study.

BACKGROUND: Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC) has been reported to account for approximately 5-16% of all GCs with good prognosis compared to EBV-negative GC. We evaluated the clinicopathological characteristics of EBVaGC including survival rate in South Korea. METHODS: A total of 4,587 patients with GC who underwent EBV in situ hybridization (EBV-ISH) were prospectively enrolled at the Seoul National University Bundang Hospital from 2003 to 2021. Age, sex, smoking status, cancer type and stage, tumor size and location, histological type, molecular features and survival information were analyzed. RESULTS: A total of 456 patients with GC (9.9%) were positive for EBV. The EBVaGC group displayed a higher proportion of males (P < 0.001), a predominant presence in the proximal stomach (P < 0.001), a higher proportion of undifferentiated cancer (P < 0.001), and a lower cancer stage (P = 0.004) than the EBV-negative group. Cox multivariate analyses revealed age (hazard ratio [HR] = 1.025, P < 0.001), tumor size (HR = 1.109, P < 0.001), and cancer stage (stage2 HR = 4.761, P < 0.001; stage3 HR = 13.286, P < 0.001; stage4 HR = 42.528, P < 0.001) as significant risk factors for GC-specific mortality, whereas EBV positivity was inversely correlated (HR = 0.620, P = 0.022). Furthermore, the EBVaGC group displayed statistically significant survival advantages over the EBV-negative cancer group in terms of both overall (P = 0.021) and GC-specific survival (P = 0.007) on the Kaplan-Meier survival curve. However, this effect was evident only in males. CONCLUSIONS: EBVaGC patients showed better prognoses despite their association with proximal location and poorly differentiated histology in male, probably due to the difference in immunity between males and females.

Adherence of PARP inhibitor for frontline maintenance therapy in primary epithelial ovarian cancer: a cross-sectional survey.

OBJECTIVE: To identify the adherence rate to poly (ADP-ribose) polymerase (PARP) inhibitors and identify factors contributing to the deterioration of adherence at our institution. METHODS: The adherence rate to PARP inhibitors was calculated using self-reported Adherence to Refills and Medications Scale questionnaires from a cross-sectional survey. Multivariable logistic regression analysis was performed to identify the factors that affected adherence. RESULTS: Of the 131 respondents, 32 (24.4%) showed non-adherence to PARP inhibitors. In the multivariable logistic regression analysis, unemployed or retired status (odds ratio [OR]=4.878; 95% confidence interval [CI]=1.528-15.572; p=0.008), patients receiving niraparib (OR=3.387; 95% CI=1.283-8.940; p=0.014), and a lower score on the quality-of-life assessment (EORTC-QLQ-OV28), which reflects a better quality of life (QOC) with a lower symptom burden (OR=1.056; 95% CI=1.027-1.086; p<0.001) were associated with high adherence to PARP inhibitors. CONCLUSION: Approximately one-fourth of patients with ovarian cancer are non-adherent to PARP inhibitors as maintenance treatment for newly diagnosed advanced ovarian cancer. The occupational status, type of PARP inhibitor, and QOC may affect adherence to PARP inhibitors.

Incidence and treatment outcomes of ovarian carcinosarcoma from the national cancer registry of Korea.

OBJECTIVE: To investigate the incidence and survival outcomes of ovarian carcinosarcoma in Korea between 1999 and 2018. METHODS: Patients diagnosed with ovarian carcinosarcoma between 1999 and 2018 were identified from the Korea Central Cancer Registry (KCCR) and their information was collected. Age-standardized incidence rates (ASRs), annual percent changes (APC), and relative survival rates of ovarian carcinosarcoma were calculated and compared to those of epithelial ovarian cancer. RESULTS: According to the KCCR, 458 cases of ovarian carcinosarcoma were detected, and accounted for 1.5% (458/30,679) of all epithelial ovarian cancers in Korea between 1999 and 2018. The ASR of ovarian carcinosarcoma between 1999 and 2018 was 0.064 per 100,000 women. The incidence rate of ovarian carcinosarcoma increased during the study period, with an ASR of 0.029 per 100,000 in 1999 and 0.073 per 100,000 in 2018. The APC of ovarian carcinosarcoma during 1999-2018 was 5.86 (p<0.001). The median overall survival (OS) of patients with ovarian carcinosarcoma was 39 months, and the 5-year OS rate was 42.5%. Among ovarian carcinosarcomas, patients with localized stages showed better clinical outcomes than those with regional or distant stages (5-year OS, 60.8%, 57.9%, and 32.8%, respectively; p<0.001). In addition, younger (<50 years) patients showed better OS than older (≥50 years) patients (5-year OS, 52.6% vs. 40.2%; p<0.001). CONCLUSION: Our nationwide registry-based study demonstrated that the incidence of ovarian carcinosarcoma increased from 1999 to 2018 in Korea. Patients with advanced-stage disease and older age (≥50 years) had poorer survival outcomes.

Transoral Endoscopy-Assisted Tongue-Lip Adhesion With Modified Tongue Base Suspension in a Pierre-Robin Sequence: A Safe and Effective Technique.

Life-threatening airway obstruction is a major concern in patients with Pierre-Robin sequence. Tongue-lip adhesion (TLA) has been used to manage airway obstruction. The authors present the case of a female neonate with Pierre-Robin sequence who presented with airway obstruction and a cleft palate. She underwent a TLA procedure with modified tongue base suspension (TBS). Endoscopy was used to check and control the traction of the tongue base to enable unobstructed self-ventilation. Positive outcomes including improved O2 saturation and weight gain were noted. The effectiveness of TLA was enhanced by using TBS with real-time endoscopy to evaluate the oropharyngeal airway space required to alleviate airway obstruction. The use of endoscopy enabled us to check and determine how much the tongue base should be tracted by manipulating the tongue anteriorly and posteriorly. The authors report transoral endoscopy-assisted TLA and modified TBS.

Risk of tuberculosis after endoscopic resection and gastrectomy in gastric cancer: nationwide population-based matched cohort study.

BACKGROUND: This study aimed to investigate the association between gastrectomy and endoscopic resection for gastric cancer and the subsequent tuberculosis incidence. METHODS: We conducted a nationwide matched cohort study using data from the Korea National Health Insurance Service from 2013 to 2019. We created two cohorts: patients who underwent gastrectomy and those who had endoscopic resection. Each patient was matched 1:1 with an unexposed individual based on index year, age, sex, income, and various comorbidities. The primary outcome was the incidence of tuberculosis during the follow-up period. RESULTS: Our study comprised 90,886 gastrectomy patients and 46,759 endoscopic resection patients. The tuberculosis incidence was significantly higher in the gastrectomy group compared to its matched non-gastrectomy group (IRR 1.69, 95% CI 1.43-1.99, p < .001). In contrast, there was no significant difference in tuberculosis incidence between the endoscopic resection group and its matched non-resection group (IRR 0.95, 95% CI 0.75-1.19, p = 0.627). The Kaplan-Meier cumulative incidence also did not differ between the two groups. However, tuberculosis incidence significantly increased in the first year after endoscopic resection. CONCLUSION: Gastrectomy for gastric cancer is associated with a higher incidence of subsequent tuberculosis, while no significant association was observed for endoscopic resection. However, tuberculosis incidence increases significantly during the first year after endoscopic resection.

Design, synthesis, and biological evaluation of HDAC6 inhibitors targeting L1 loop and serine 531 residue.

Histone deacetylases (HDACs) are a group of enzymes that remove acetyl groups from histones, leading to the silencing of genes. Targeting specific isoforms of HDACs has emerged as a promising approach for cancer therapy, as it can overcome drawbacks associated with pan-HDAC inhibitors. HDAC6 is a unique HDAC isoform that deacetylates non-histone proteins and is primarily located in the cytoplasm. It also has two catalytic domains and a zinc-finger ubiquitin binding domain (Zf-UBD) unlike other HDACs. HDAC6 plays a critical role in various cellular processes, including cell motility, protein degradation, cell proliferation, and transcription. Hence, the deregulation of HDAC6 is associated with various malignancies. In this study, we report the design and synthesis of a series of HDAC6 inhibitors. We evaluated the synthesized compounds by HDAC enzyme assay and identified that compound 8g exhibited an IC50 value of 21 nM and 40-fold selective activity towards HDAC6. We also assessed the effect of compound 8g on various cell lines and determined its ability to increase protein acetylation levels by Western blotting. Furthermore, the increased acetylation of α-tubulin resulted in microtubule polymerization and changes in cell morphology. Our molecular docking study supported these findings by demonstrating that compound 8g binds well to the catalytic pocket via L1 loop of HDAC6 enzyme. Altogether, compound 8g represents a preferential HDAC6 inhibitor that could serve as a lead for the development of more potent and specific inhibitors.