Purpose: Developmentally regulated GTP-binding protein 2 (DRG2) regulates microtubule dynamics and G2/M arrest during docetaxel treatment. Poly ADP-ribose polymerase (PARP) acts as an important repair system for DNA damage caused by docetaxel treatment. This study investigated whether DRG2 expression affects response to PARP inhibitors (olaparib) using prostate cancer cell lines PC3, DU145, LNCaP-FGC, and LNCaP-LN3. Materials and Methods: The cell viability and DRG2 expression levels were assessed using colorimetric-based cell viability assay and western blot. Cells were transfected with DRG2 siRNA, and pcDNA6/V5-DRG2 was used to overexpress DRG2. Flow cytometry was applied for cell cycle assay and apoptosis analysis using the Annexing V cell death assay. Results: The expression of DRG2 was highest in LNCaP-LN3 and lowest in DU145 cells. Expressions of p53 in PC3, DU145, and the two LNCaP cell lines were null-type, high-expression, and medium-expression, respectively. In PC3 (DRG2 high, p53 null) cells, docetaxel increased G2/M arrest without apoptosis; however, subsequent treatment with olaparib promoted apoptosis. In DU145 and LNCaP-FGC (DRG2 low), docetaxel increased sub-G1 but not G2/M arrest and induced apoptosis, whereas olaparib had no additional effect. In LNCaP-LN3 (DRG2 high, p53 wild-type), docetaxel increased sub-G1 and G2/M arrest, furthermore olaparib enhanced cell death. Docetaxel and olaparib combination treatment had a slight effect on DRG2 knockdown PC3, but increased apoptosis in DRG2-overexpressed DU145 cells. Conclusions DRG2 and p53 expressions play an important role in prostate cancer cell lines treated with docetaxel, and DRG2 levels can predict the response to PARP inhibitors.

Objective: : Intracerebral hemorrhage (ICH) accompanies higher mortality rates than other type of stroke. This study aimed to investigate the association between hospital volume and mortality for cases of ICH. Methods: : We used nationwide data from 2013 to 2018 to compare high-volume hospitals (≥32 admissions/year) and low-volume hospitals (<32 admissions/year). We tracked patients’ survival at 3-month, 1-year, 2-year, and 4-year endpoints. The survival of ICH patients was analyzed at 3-month, 1-year, 2-year, and 4-year endpoints using Kaplan-Meier survival analysis. Multivariable logistic regression analysis and Cox regression analysis were performed to determine predictive factors of poor outcomes at discharge and death. Results: : Among 9086 ICH patients who admitted to hospital during 18-month period, 6756 (74.4%) and 2330 (25.6%) patients were admitted to high-volume and low-volume hospitals. The mortality of total ICH patients was 18.25%, 23.87%, 27.88%, and 35.74% at the 3-month, 1-year, 2-year, and 4-year, respectively. In multivariate logistic analysis, high-volume hospitals had lower poor functional outcome at discharge than low-volume hospitals (odds ratio, 0.80; 95% confidence interval, 0.72–0.91; p<0.001). In the Cox analysis, high-volume hospitals had significantly lower 3-month, 1-year, 2-year, and 4-year mortality than low-volume hospitals (p<0.05). Conclusion : The poor outcome at discharge, short- and long-term mortality in ICH patients differed according to hospital volume. High-volume hospitals showed lower rates of mortality for ICH patients, particularly those with severe clinical status.

OBJECTIVES: We estimated the population prevalence of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including unreported infections, through a Korea Seroprevalence Study of Monitoring of SARS-CoV-2 Antibody Retention and Transmission (K-SEROSMART) in 258 communities throughout Korea. METHODS: In August 2022, a survey was conducted among 10,000 household members aged 5 years and older, in households selected through two stage probability random sampling. During face-to-face household interviews, participants self-reported their health status, COVID-19 diagnosis and vaccination history, and general characteristics. Subsequently, participants visited a community health center or medical clinic for blood sampling. Blood samples were analyzed for the presence of antibodies to spike proteins (anti-S) and antibodies to nucleocapsid proteins (anti-N) SARS-CoV-2 proteins using an electrochemiluminescence immunoassay. To estimate the population prevalence, the PROC SURVEYMEANS statistical procedure was employed, with weighting to reflect demographic data from July 2022. RESULTS: In total, 9,945 individuals from 5,041 households were surveyed across 258 communities, representing all basic local governments in Korea. The overall population-adjusted prevalence rates of anti-S and anti-N were 97.6% and 57.1%, respectively. Since the Korea Disease Control and Prevention Agency has reported a cumulative incidence of confirmed cases of 37.8% through July 31, 2022, the proportion of unreported infections among all COVID-19 infection was suggested to be 33.9%. CONCLUSIONS The K-SEROSMART represents the first nationwide, community-based seroepidemiologic survey of COVID-19, confirming that most individuals possess antibodies to SARS-CoV-2 and that a significant number of unreported cases existed. Furthermore, this study lays the foundation for a surveillance system to continuously monitor transmission at the community level and the response to COVID-19.

Background: and Purpose Moderate-intensity statin plus ezetimibe versus high-intensity statin alone may provide a greater low-density lipoprotein cholesterol (LDL-C) reduction in patients with recent ischemic stroke. Methods: This randomized, open-label, controlled trial assigned patients with recent ischemic stroke <90 days to rosuvastatin/ezetimibe 10/10 mg once daily (ROS10/EZT10) or to rosuvastatin 20 mg once daily (ROS20). The primary endpoint was LDL-C reduction ≥50% from baseline at 90 days. Key secondary endpoints were LDL-C <70 mg/dL and multiple lipid goal achievement, and composite of major vascular events. Results: Of 584 randomized, 530 were included in the modified intention-to-treat analysis. The baseline LDL-C level was 130.2±34.7 mg/dL in the ROS10/EZT10 group and 131.0±33.9 mg/dL in the ROS20 group. The primary endpoint was achieved in 198 patients (72.5%) in the ROS10/EZT10 group and 148 (57.6%) in the ROS20 group (odds ratio [95% confidence interval], 1.944 [1.352–2.795]; P= 0.0003). LDL-C level <70 mg/dL was achieved in 80.2% and 65.4% in the ROS10/EZT10 and ROS20 groups (P=0.0001). Multiple lipid goal achievement rate was 71.1% and 53.7% in the ROS10/EZT10 and ROS20 groups (P<0.0001). Major vascular events occurred in 1 patient in the ROS10/EZT10 group and 9 in the ROS20 group (P=0.0091). The adverse event rates did not differ between the two groups. Conclusion Moderate-intensity rosuvastatin plus ezetimibe was superior to high-intensity rosuvastatin alone for intensive LDL-C reduction in patients with recent ischemic stroke. With the combination therapy, more than 70% of patients achieved LDL-C reduction ≥50% and 80% had an LDL-C <70 mg/dL at 90 days.

The aim of this study was to develop evidence-based recommendations for determining the surgical extent in patients with locally invasive differentiated thyroid cancer (DTC). Locally invasive DTC with gross extrathyroidal extension invading surrounding anatomical structures may lead to several functional deficits and poor oncological outcomes. At present, the optimal extent of surgery in locally invasive DTC remains a matter of debate, and there are no adequate guidelines. On October 8, 2021, four experts searched the PubMed, Embase, and Cochrane Library databases; the identified papers were reviewed by 39 experts in thyroid and head and neck surgery. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the quality of evidence, and to develop and report recommendations. The strength of a recommendation reflects the confidence of a guideline panel that the desirable effects of an intervention outweigh any undesirable effects, across all patients for whom the recommendation is applicable. After completing the draft guidelines, Delphi questionnaires were completed by members of the Korean Society of Head and Neck Surgery. Twenty-seven evidence-based recommendations were made for several factors, including the preoperative workup; surgical extent of thyroidectomy; surgery for cancer invading the strap muscles, recurrent laryngeal nerve, laryngeal framework, trachea, or esophagus; and surgery for patients with central and lateral cervical lymph node involvement. Evidence-based guidelines were devised to help clinicians make safer and more efficient clinical decisions for the optimal surgical treatment of patients with locally invasive DTC.

Background: This study investigated the results of component asymmetry (CA) in bilateral cementless total hip arthroplasty (THA). Methods: This study included 300 patients, who underwent bilateral cementless THA between April 2000 and December 2017. They were divided into the component symmetry (CS) and CA groups; CA group was sub-classified into acetabular component asymmetry (ACA) and femoral component asymmetry (FCA). Radiologic and clinical outcomes of the CA group were compared with those of the CS group. Results: The incidence of CA was 25.7% (77/300 patients), including 55 patients with ACA, 34 patients with FCA, and 12 with both components asymmetric. The mean time interval between operations in the CA group was significantly longer than that in the CS group (p < 0.001). The mean differences in horizontal and vertical distances from teardrop to the center of rotation of the acetabular component between both hips in the ACA group were significantly larger than those in the CS group (p = 0.033 and p < 0.001, respectively). The mean femoral component alignment angle difference between both hips was significantly larger in the FCA group than in the CS group (p < 0.001). The mean Harris Hip Score at last follow-up of the CA group was similar to that of the CS group. Conclusions CA in patients undergoing bilateral cementless THA was not rare, especially with a longer time interval between operations. Regardless of CA, when stable fixation of the components was achieved, satisfactory radiologic and clinical outcomes were obtained.

Purpose: Outcome analysis of urachal cancer (UraC) is limited due to the scarcity of cases and different staging methods compared to urothelial bladder cancer (UroBC). We attempted to assess survival outcomes of UraC and compare to UroBC after stage-matched analyses. Materials and Methods: Total 203 UraC patients from a multicenter database and 373 UroBC patients in single institution from 2000 to 2018 were enrolled (median follow-up, 32 months). Sheldon stage conversion to corresponding TNM staging for UraC was conducted for head-to-head comparison to UroBC. Perioperative clinical variables and pathological results were recorded. Stage-matched analyses for survival by stage were conducted. Results: UraC patients were younger (mean age, 54 vs. 67 years; p < 0.001), with 163 patients (80.3%) receiving partial cystectomy and 23 patients (11.3%) radical cystectomy. UraC was more likely to harbor ≥ pT3a tumors (78.8% vs. 41.8%). While 5-year recurrence-free survival, cancer-specific survival (CSS) and overall survival were comparable between two groups (63.4%, 67%, and 62.1% in UraC and 61.5%, 75.9%, and 67.8% in UroBC, respectively), generally favorable prognosis for UraC in lower stages (pT1-2) but unfavorable outcomes in higher stages (pT4) compared to UroBC was observed, although only 5-year CSS in ≥ pT4 showed statistical significance (p=0.028). Body mass index (hazard ratio [HR], 0.929), diabetes mellitus (HR, 1.921), pathologic T category (HR, 3.846), and lymphovascular invasion (HR, 1.993) were predictors of CSS for all patients. Conclusion Despite differing histology, UraC has comparable prognosis to UroBC with relatively favorable outcome in low stages but worse prognosis in higher stages. The presented system may be useful for future grading and risk stratification of UraC.

Background: This study aimed to identify the specific T cell co-stimulatory and co-inhibitory factors that play prognostic roles in patients with glioblastoma. Additionally, the unique histone H3 modification enzymes that regulate the expression levels of these specific costimulatory and co-inhibitory factors were investigated. Methods: The medical records of 84 patients newly diagnosed with glioblastoma at our institution from January 2006 to December 2020 were retrospectively reviewed.Immunohistochemical (IHC) staining for T cell co-stimulatory factors (CD27, CD28, CD137, OX40, and ICOS), T cell co-inhibitory factors (CTLA4, PD1, PD-L1, TIM3, and CD200R), and histone H3 lysine modification enzymes (MLL4, RIZ, EZH1, NSD2, KDM5c, JMJD1a, UTX, and JMJD5) was performed on archived paraffin-embedded tissues obtained by biopsy or resection. Quantitative real time-polymerase chain reaction (qRT-PCR) was performed for specific factors, which demonstrated causal relationships, in order to validate the findings of the IHC examinations. Results: The mean follow-up duration was 27.5 months (range, 4.1–43.5 months). During this period, 76 patients (90.5%) died, and the mean OS was 19.4 months (95% confidence interval, 16.3–20.9 months). Linear positive correlations were observed between the expression levels of CD28 and JMJD1a (R2 linear = 0.982) and those of CD137 and UTX (R2 linear = 1.528). Alternatively, significant negative correlations were observed between the expression levels of CTLA4 and RIZ (R2 linear = −1.746) and those of PD-L1 and EZH1 (R2 linear = −2.118); relationships were confirmed by qRT-PCR. In the multivariate analysis, increased expression levels of CD28 (P = 0.042), and CD137 (P = 0.009), and decreased expression levels of CTLA4 (P = 0.003), PD-L1 (P = 0.020), and EZH1 (P = 0.040) were significantly associated with longer survival. Conclusion These findings suggest that the expression of certain T cell co-stimulatory factors, such as CD28 and CD 137, and co-inhibitory factors, such as CTLA4 and PD-L1 are associated with prognosis of glioblastoma patients.

Background: Current international guidelines recommend against deep sedation as it is associated with worse outcomes in the intensive care unit (ICU). However, in Korea the prevalence of deep sedation and its impact on patients in the ICU are not well known. Methods: From April 2020 to July 2021, a multicenter, prospective, longitudinal, noninterventional cohort study was performed in 20 Korean ICUs. Sedation depth extent was divided into light and deep using a mean Richmond Agitation–Sedation Scale value within the first 48 hours. Propensity score matching was used to balance covariables; the outcomes were compared between the two groups. Results: Overall, 631 patients (418 [66.2%] and 213 [33.8%] in the deep and light sedation groups, respectively) were included. Mortality rates were 14.1% and 8.4% in the deep and light sedation groups (P = 0.039), respectively. Kaplan-Meier estimates showed that time to extubation (P < 0.001), ICU length of stay (P = 0.005), and death P = 0.041) differed between the groups. After adjusting for confounders, early deep sedation was only associated with delayed time to extubation (hazard ratio [HR], 0.66; 95% confidence inter val [CI], 0.55– 0.80; P < 0.001). In the matched cohort, deep sedation remained significantly associated with delayed time to extubation (HR, 0.68; 95% 0.56–0.83; P < 0.001) but was not associated with ICU length of stay (HR, 0.94; 95% CI, 0.79–1.13; P = 0.500) and in-hospital mortality (HR, 1.19; 95% CI, 0.65–2.17; P = 0.582). Conclusion In many Korean ICUs, early deep sedation was highly prevalent in mechanically ventilated patients and was associated with delayed extubation, but not prolonged ICU stay or in-hospital death.