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.

Purpose: Real-world experience with tocilizumab in combination with dexamethasone in patients with severe coronavirus disease (COVID-19) needs to be investigated. Materials and Methods: A retrospective cohort study was conducted to evaluate the effect of severity-adjusted dosing of dexamethasone in combination with tocilizumab for severe COVID-19 from August 2020 to August 2021. The primary endpoint was 30-day clinical recovery, which was defined as no oxygen requirement or referral after recovery. Results: A total of 66 patients were evaluated, including 33 patients in the dexamethasone (Dexa) group and 33 patients in the dexamethasone plus tocilizumab (DexaToci) group. The DexaToci group showed a statistically significant benefit in 30-day clinical recovery, compared to the Dexa group (p=0.024). In multivariable analyses, peak FiO2 within 3 days and tocilizumab combination were consistently significant for 30-day recovery (all p<0.05). The DexaToci group showed a significantly steeper decrease in FiO2 (-4.2±2.6) than the Dexa group (−2.7±2.6; p=0.021) by hospital day 15. The duration of oxygen requirement was significantly shorter in the DexaToci group than the Dexa group (median, 10.0 days vs. 17.0 days; p=0.006). Infectious complications and cellular and humoral immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the convalescence stage were not different between the two groups. Conclusion A combination of severity-adjusted dexamethasone and tocilizumab for the treatment of severe COVID-19 improved clinical recovery without increasing infectious complications or hindering the immune response against SARS-CoV-2.

Purpose: Eph receptors are differentially expressed in numerous malignant tumors. This study intended to analyze the roles of EphB receptors (EphB2, B3, and B4) in urinary bladder cancer. Materials and Methods: Tissue microarray-based immunohistochemical analysis was used to investigate the expression patterns of EphB2, EphB3, and EphB4 in 154 bladder cancer specimens. Immunohistochemical staining was conducted examining the extent of stained cells and staining intensity. EphB was considered to be highly expressed when the intensity of staining was more than moderate in >25% of cells in the tissue section. Small interfering RNA (siRNA) was used to knock down EphB expression in bladder cancer cell lines (T24, 5637) to determine the effects of EphB on tumor cell invasion, proliferation, and migration. Results: EphB receptors (B2, B3, and B4) were detected in 40.9% (EphB2, 63/154), 71.4% (EphB3, 110/154), and 53.2% (EphB4, 82/154) of bladder cancer specimens. Low expression of EphB2, B3, and B4 receptors were significantly associated with higher tumor grade (EphB2, p<0.001; EphB3, p=0.032; EphB4, p<0.001) and muscular invasion (EphB2, p=0.002; EphB3, p=0.009; EphB4, p<0.001). No obvious correlation was observed with other clinicopathological variables, such as age, sex, recurrence, lymph node involvement, metastasis, and overall survival. Inactivation of EphB receptors by siRNA transfection increased cell viability, tumor cell invasion, proliferation, and migration in comparison with untransfected cancer cells. Conclusion Low expression of EphB receptors (B2, B3, and B4) can be a predictive marker for muscular invasion of bladder cancer.

Nonpharmaceutical interventions (e.g., social distancing) are recommended to prevent the spread of respiratory viruses. However, few epidemiological studies have assessed whether social distancing in actual settings reduces the disease burden of severe acute respiratory infections (SARIs) in the general population. Accordingly, we aimed to assess associations between nationwide social distancing for coronavirus disease 2019 (COVID-19) and non-COVID-19 SARIs. We collected data on SARI epidemiologic characteristics recorded from January 2018 through December 2020 from the nationwide sentinel SARI surveillance data maintained by the Korea Disease Control and Prevention Agency. The number of SARIs per 1000 hospitalized patients decreased significantly to 18.61, 18.15, and 6.25 in 2018, 2019, and 2020 (p<0.001), respectively, during the surveillance period of 3 years. The number of intensive care unit admissions associated with SARIs per 1000 hospitalized patients was 0.83, 0.69, and 0.54 in 2018, 2019, and 2020 (p< 0.001), respectively, and the number of SARI-associated mortalities per 1000 patients was 0.42, 0.29, and 0.27 in 2018, 2019, and 2020 (p<0.001), respectively. Moreover, SARIs had two peak seasons in 2 years of the surveillance period (2018 and 2019). However, seasonality was not observed since social distancing was initiated. Our sentinel surveillance data demonstrated a remarkable reduction in SARI disease burden and a change in seasonality following the implementation of nationwide social distancing. Accordingly, we suggest that social distancing could be effective in forthcoming seasonal epidemics of non-COVID-19 origin, although the impact thereof on other aspects of society needs to be carefully considered.

Purpose: Natural killer (NK) cells are innate immune cells with antitumor activity. NKG2D is the most important activating receptor expressed on the NK cell surface; this receptor binds to the ligands MICA/B and ULBPs to activate NK cells. The current study aimed to evaluate the expression of NKG2D by NK cells, and to the evaluate expression of its ligands in ovarian carcinomas; it also examined the clinical relevance of NK receptor/ligand expression by analyzing the relationship between expression, clinicopathological parameters, and prognosis. Materials and Methods: Formalin-fixed paraffin-embedded archival ovarian high-grade serous carcinoma (HGSC, n=79) tissue samples were used for tissue microarray analysis. The expressions of NK cell markers (CD56 and NKG2D) and NKG2D ligands (MICA/B, ULBP1, ULBP3, and ULBP2/5/6) in carcinoma tissues were evaluated by immunohistochemical staining, and the association between these results and clinical prognostic parameters was analyzed statistically. Results: ULBP1 was highly expressed in 51 cases (64.6%), and ULBP2/5/6 was highly expressed in 56 cases (70.9%) of HGSC. High expression of ULBP1 and ULBP2/5/6 was significantly associated with lower recurrence of HGSC, whereas high expression of ULBP3 was significantly associated with higher recurrence. Multivariate Cox regression analysis revealed that high expression of ULBP1 was associated with increased overall survival and a decreased hazard ratio (0.150, p=0.044), suggesting that it is an independent predictor of better survival. Conclusion High expression of ULBP1 predicts a better prognosis for HGSC, suggesting that ULBP1 expression could be a novel prognostic indicator in this subset of carcinomas.

Purpose: Eph receptors are differentially expressed in numerous malignant tumors. This study intended to analyze the roles of EphB receptors (EphB2, B3, and B4) in urinary bladder cancer. Materials and Methods: Tissue microarray-based immunohistochemical analysis was used to investigate the expression patterns of EphB2, EphB3, and EphB4 in 154 bladder cancer specimens. Immunohistochemical staining was conducted examining the extent of stained cells and staining intensity. EphB was considered to be highly expressed when the intensity of staining was more than moderate in >25% of cells in the tissue section. Small interfering RNA (siRNA) was used to knock down EphB expression in bladder cancer cell lines (T24, 5637) to determine the effects of EphB on tumor cell invasion, proliferation, and migration. Results: EphB receptors (B2, B3, and B4) were detected in 40.9% (EphB2, 63/154), 71.4% (EphB3, 110/154), and 53.2% (EphB4, 82/154) of bladder cancer specimens. Low expression of EphB2, B3, and B4 receptors were significantly associated with higher tumor grade (EphB2, p<0.001; EphB3, p=0.032; EphB4, p<0.001) and muscular invasion (EphB2, p=0.002; EphB3, p=0.009; EphB4, p<0.001). No obvious correlation was observed with other clinicopathological variables, such as age, sex, recurrence, lymph node involvement, metastasis, and overall survival. Inactivation of EphB receptors by siRNA transfection increased cell viability, tumor cell invasion, proliferation, and migration in comparison with untransfected cancer cells. Conclusion Low expression of EphB receptors (B2, B3, and B4) can be a predictive marker for muscular invasion of bladder cancer.

Nonpharmaceutical interventions (e.g., social distancing) are recommended to prevent the spread of respiratory viruses. However, few epidemiological studies have assessed whether social distancing in actual settings reduces the disease burden of severe acute respiratory infections (SARIs) in the general population. Accordingly, we aimed to assess associations between nationwide social distancing for coronavirus disease 2019 (COVID-19) and non-COVID-19 SARIs. We collected data on SARI epidemiologic characteristics recorded from January 2018 through December 2020 from the nationwide sentinel SARI surveillance data maintained by the Korea Disease Control and Prevention Agency. The number of SARIs per 1000 hospitalized patients decreased significantly to 18.61, 18.15, and 6.25 in 2018, 2019, and 2020 (p<0.001), respectively, during the surveillance period of 3 years. The number of intensive care unit admissions associated with SARIs per 1000 hospitalized patients was 0.83, 0.69, and 0.54 in 2018, 2019, and 2020 (p< 0.001), respectively, and the number of SARI-associated mortalities per 1000 patients was 0.42, 0.29, and 0.27 in 2018, 2019, and 2020 (p<0.001), respectively. Moreover, SARIs had two peak seasons in 2 years of the surveillance period (2018 and 2019). However, seasonality was not observed since social distancing was initiated. Our sentinel surveillance data demonstrated a remarkable reduction in SARI disease burden and a change in seasonality following the implementation of nationwide social distancing. Accordingly, we suggest that social distancing could be effective in forthcoming seasonal epidemics of non-COVID-19 origin, although the impact thereof on other aspects of society needs to be carefully considered.

Background and Objectives: Despite recent improvements in advanced life support, the overall survival rate after cardiac arrest remains low. We aimed to examine the association of a multidisciplinary team approach with clinical outcomes in patients undergoing extracorporeal cardiopulmonary resuscitation (ECPR) in the emergency department (ED). Methods: This retrospective, single-center, observational study included 125 patients who underwent ECPR in the ED between May 2004–December 2018. In January 2014, our institution implemented a multidisciplinary extracorporeal membrane oxygenation (ECMO) team. Eligible patients were classified into pre-ECMO-team (n=65) and post-ECMO-team (n=60) groups. The primary outcome was in-hospital mortality. Results: In-hospital mortality (72.3% vs. 58.3%, p=0.102) and poor neurological outcomes (78.5% vs. 68.3%, p=0.283) did not differ significantly between the pre- and post-ECMOteam groups. However, among the 60 patients who experienced in-hospital cardiac arrest,in-hospital mortality (75.8% vs. 40.7%, p=0.006) and poor neurological outcomes (78.8% vs. 48.1%, p=0.015) significantly decreased after the multidisciplinary team formation.Multivariable logistic regression analysis showed that the multidisciplinary team approach (adjusted odds ratio, 0.20; 95% confidence interval, 0.07–0.61; p=0.005) was an independent prognostic factor for in-hospital mortality in in-hospital cardiac arrest patients. Conclusions A multidisciplinary team approach was associated with improved clinical outcomes in in-hospital cardiac arrest patients undergoing ECPR in the ED. These findings may help in improving the selection criteria for ECPR in the ED. Further studies to overcome the study limitations may help improving the outcomes of out-of-hospital cardiac arrest patients.

Purpose: The aim of this study was to analyze the temporal change of resuscitation fluid use based on all fluids administered in a surgical intensive care unit (ICU). Methods: The administration of resuscitation fluid to all patients admitted to a surgical ICU of a tertiary referral hospital was investigated from 2008 to 2015. The types and volumes of fluid, and laboratory data taken within 7 days after ICU admission were evaluated. Resuscitation fluids were defined as fluids infused according to stat orders, rather than routine orders. Results: There were a total of 8,885 admissions to the ICU for 7,886 patients. The volumetric proportion of crystalloid to total resuscitation fluids increased significantly over the study period (p < 0.001; 79.6% in 2008; 93.7% in 2015). Although the proportion of 0.9% saline to crystalloids decreased, that of balanced solutions increased (p < 0.001; 29.5% in 2008; 55.6% in 2015). The use of colloids decreased from 20.4% in 2008, to 6.3% in 2015 (p < 0.001). Proportions calculated using the number of individual fluids administered revealed trends similar to those calculated using volumetric data. The amount of infused 0.9% saline was weakly correlated with the lowest blood pH and the highest serum chloride levels (ρ = -0.26 and 0.19, respectively). Conclusion Changes in the trends of fluid resuscitation practice were noted in a single surgical ICU over the 8-year study period. Crystalloid use increased owing to a rise in the utilization of balanced solutions with a downward trend in colloid use.

Purpose: The aim of this study was to analyze the temporal change of resuscitation fluid use based on all fluids administered in a surgical intensive care unit (ICU). Methods: The administration of resuscitation fluid to all patients admitted to a surgical ICU of a tertiary referral hospital was investigated from 2008 to 2015. The types and volumes of fluid, and laboratory data taken within 7 days after ICU admission were evaluated. Resuscitation fluids were defined as fluids infused according to stat orders, rather than routine orders. Results: There were a total of 8,885 admissions to the ICU for 7,886 patients. The volumetric proportion of crystalloid to total resuscitation fluids increased significantly over the study period (p < 0.001; 79.6% in 2008; 93.7% in 2015). Although the proportion of 0.9% saline to crystalloids decreased, that of balanced solutions increased (p < 0.001; 29.5% in 2008; 55.6% in 2015). The use of colloids decreased from 20.4% in 2008, to 6.3% in 2015 (p < 0.001). Proportions calculated using the number of individual fluids administered revealed trends similar to those calculated using volumetric data. The amount of infused 0.9% saline was weakly correlated with the lowest blood pH and the highest serum chloride levels (ρ = -0.26 and 0.19, respectively). Conclusion Changes in the trends of fluid resuscitation practice were noted in a single surgical ICU over the 8-year study period. Crystalloid use increased owing to a rise in the utilization of balanced solutions with a downward trend in colloid use.