We aimed to identify blood lymphocytes as a prognostic factor for survival in patients with locally advanced stage III non-small cell lung cancer (NSCLC) treated with concurrent chemoradiotherapy (CCRT). This is a secondary study of 196 patients enrolled in the Korean Radiation Oncology Group 0903 phase III clinical trial to evaluate the prognostic significance of circulating blood lymphocyte levels. The median total lymphocyte count (TLC) reduction ratio during CCRT was 0.74 (range: 0.29-0.97). In multivariate analysis, patient age (p=0.014) and gross tumor volume (GTV, p=0.031) were significant factors associated with overall survival, while TLC reduction (p=0.018) and pretreatment neutrophil-to-lymphocyte ratio (NLR; p=0.010) were associated with progression-free survival (PFS). In multivariate logistic regression analysis, pretreatment NLR, GTV, and heart V20 were significantly associated with TLC reduction. Immunohistochemical analysis of programmed death ligand 1 and CD8 expression on T cells was performed on 84 patients. CD8 expression was not significantly associated with the pretreatment lymphocyte count (p=0.673), and PDL1 expression was not significantly associated with OS or PFS. Univariate analysis revealed that high CD8 expression in TILs was associated with favorable OS and was significantly associated with favorable PFS (p=0.032). TLC reduction during CCRT is a significant prognostic factor for PFS, and heart V20 is significantly associated with TLC reduction. Thus, in the era of immunotherapy, constraining the volume of the radiation dose to the whole heart must be prioritized for the better survival outcomes.

Viral load and the duration of viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are important determinants of the transmission of coronavirus disease 2019.In this study, we examined the effects of viral doses on the lung and spleen of K18-hACE2 transgenic mice by temporal histological and transcriptional analyses. Approximately, 1×105 plaque-forming units (PFU) of SARS-CoV-2 induced strong host responses in the lungs from 2 days post inoculation (dpi) which did not recover until the mice died, whereas responses to the virus were obvious at 5 days, recovering to the basal state by 14 dpi at 1×102 PFU. Further, flow cytometry showed that number of CD8+ T cells continuously increased in 1×102 PFU-virusinfected lungs from 2 dpi, but not in 1×105 PFU-virus-infected lungs. In spleens, responses to the virus were prominent from 2 dpi, and number of B cells was significantly decreased at 1×105PFU; however, 1×102 PFU of virus induced very weak responses from 2 dpi which recovered by 10 dpi. Although the defense responses returned to normal and the mice survived, lung histology showed evidence of fibrosis, suggesting sequelae of SARS-CoV-2 infection. Our findings indicate that specific effectors of the immune response in the lung and spleen were either increased or depleted in response to doses of SARS-CoV-2. This study demonstrated that the response of local and systemic immune effectors to a viral infection varies with viral dose, which either exacerbates the severity of the infection or accelerates its elimination.

Objective: : The Act on Life-Sustaining Treatment (LST) decisions for end-of-life patients has been effective since February 2018. An increasing number of patients and their families want to withhold or withdraw from LST when medical futility is expected. This study aimed to investigate the status of the Act on LST decisions for patients with acute cerebrovascular disease at a single hospital. Methods: : Between January 2017 and December 2021, 227 patients with acute cerebrovascular diseases, including hemorrhagic stroke (n=184) and ischemic stroke (n=43), died at the hospital. The study period was divided into the periods before and after the Act. Results: : The duration of hospitalization decreased after the Act was implemented compared to before (15.9±16.1 vs. 11.2±18.6 days, p=0.127). The rate of obtaining consent for the LST plan tended to increase after the Act (139/183 [76.0%] vs. 27/44 [61.4%], p=0.077). Notably, none of the patients made an LST decision independently. Ventilator withdrawal was more frequently performed after the Act than before (52/183 [28.4%] vs. 0/44 [0%], p<0.001). Conversely, the rate of organ donation decreased after the Act was implemented (5/183 [2.7%] vs. 6/44 [13.6%], p=0.008). Refusal to undergo surgery was more common after the Act was implemented than before (87/149 [58.4%] vs. 15/41 [36.6%], p=0.021) among the 190 patients who required surgery. Conclusion : After the Act on LST decisions was implemented, the rate of LST withdrawal increased in patients with acute cerebrovascular disease. However, the decision to withdraw LST was made by the patient’s family rather than the patient themselves. After the execution of the Act, we also observed an increased rate of refusal to undergo surgery and a decreased rate of organ donation. The Act on LST decisions may reduce unnecessary treatments that prolong end-of-life processes without a curative effect. However, the widespread application of this law may also reduce beneficial treatments and contribute to a decline in organ donation.

Purpose: Renal tumors account for approximately 7% of all childhood cancers. These include Wilms tumor (WT), clear cell sarcoma of the kidney (CCSK), malignant rhabdoid tumor of the kidney (MRTK), renal cell carcinoma (RCC), congenital mesoblastic nephroma (CMN) and other rare tumors. We investigated the epidemiology of pediatric renal tumors in Korea. Materials and Methods: From January 2001 to December 2015, data of pediatric patients (0–18 years) newly-diagnosed with renal tumors at 26 hospitals were retrospectively analyzed. Results: Among 439 patients (male, 240), the most common tumor was WT (n=342, 77.9%), followed by RCC (n=36, 8.2%), CCSK (n=24, 5.5%), MRTK (n=16, 3.6%), CMN (n=12, 2.7%), and others (n=9, 2.1%). Median age at diagnosis was 27.1 months (range 0-225.5) and median follow-up duration was 88.5 months (range 0-211.6). Overall, 32 patients died, of whom 17, 11, 1, and 3 died of relapse, progressive disease, second malignant neoplasm, and treatment-related mortality. Five-year overall survival and event free survival were 97.2% and 84.8% in WT, 90.6% and 82.1% in RCC, 81.1% and 63.6% in CCSK, 60.3% and 56.2% in MRTK, and 100% and 91.7% in CMN, respectively (p < 0.001). Conclusion The pediatric renal tumor types in Korea are similar to those previously reported in other countries. WT accounted for a large proportion and survival was excellent. Non-Wilms renal tumors included a variety of tumors and showed inferior outcome, especially MRTK. Further efforts are necessary to optimize the treatment and analyze the genetic characteristics of pediatric renal tumors in Korea.

Background: The epidemiology of pathogenic bacteria varies according to the socioeconomic status and antimicrobial resistance status. However, longitudinal epidemiological studies to evaluate the changes in species distribution and antimicrobial susceptibility of pathogenic bacteria nationwide are lacking. We retrospectively investigated the nationwide trends in species distribution and antimicrobial susceptibility of pathogenic bacteria over the last 20 years in Korea. Methods: From 1997 to 2016, annual cumulative antimicrobial susceptibility and species distribution data were collected from 12 university hospitals in five provinces and four metropolitan cities in South Korea. Results: The prevalence of Staphylococcus aureus was the highest (13.1%) until 2012 but decreased to 10.3% in 2016, consistent with the decrease in oxacillin resistance from 76.1% in 2008 to 62.5% in 2016. While the cefotaxime resistance of Escherichia coli increased from 9.0% in 1997 to 34.2% in 2016, E. coli became the most common species since 2013, accounting for 14.5% of all isolates in 2016. Pseudomonas aeruginosa and Acinetobacter baumannii rose to third and fifth places in 2008 and 2010, respectively, while imipenem resistance increased from 13.9% to 30.8% and 0.7% to 73.5% during the study period, respectively.Streptococcus agalactiae became the most common pathogenic streptococcal species in 2016, as the prevalence of Streptococcus pneumoniae decreased since 2010. During the same period, pneumococcal penicillin susceptibility decreased to 79.0%, and levofloxacin susceptibility of S. agalactiae decreased to 77.1% in 2016. Conclusion The epidemiology of pathogenic bacteria has changed significantly over the past 20 years according to trends in antimicrobial resistance in Korea. Efforts to confine antimicrobial resistance would change the epidemiology of pathogenic bacteria and, consequently, the diagnosis and treatment of infectious diseases.

Objective: : With the recent increase in mechanical thrombectomy (MT) for acute ischemic stroke (AIS), the role of neurosurgeons in AIS treatment has become increasingly important. This study aimed to assess the outcomes of patients with AIS treated by neurosurgeons and neurologists in the emergency room (ER) of a tertiary hospital in South Korea. Methods: : From January 2020 to June 2021, 536 patients with AIS within 24 hours of symptom onset were admitted to our hospital via the ER. Based on the type of doctors who provided initial care for AIS in the ER, patients were divided into two groups : (a) neurosurgeon group (n=119, 22.2%) and (b) neurologist group (n=417, 77.8%). Results: : Intravenous tissue plasminogen activator (tPA) was administered in 82 (15.3%) of 536 patients (n=17 [14.3%] in the neurosurgeon group and n=65 [15.6%] in the neurologist group). The door-to-tPA time was not significantly different between both groups (median, 53 minutes; interquartile range [IQR], 45–58 vs. median, 54 minutes; IQR, 46–74; p=0.372). MT was performed in 69 patients (12.9%) (n=25, 36.2% in the neurosurgeon group and n=44, 63.8% in the neurologist group). The neurosurgeon group achieved a shorter door-to-puncture time than the neurologist group (median, 115 minutes; IQR, 107–151 vs. median, 162 minutes; IQR, 117–189; p=0.049). Good clinical outcomes (3-month modified Rankin Scale 0–2) did not differ significantly between the two groups (96/119 [80.7%] vs. 322/417 [77.2%], p=0.454). Conclusion : The neurosurgeon group showed similar door-to-treatment time and clinical outcomes to the neurologist group in patients with AIS in the ER. This study suggests that neurosurgeons have comparable abilities to care for patients with AIS in the ER.

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: The Omicron variant has become the most prevalent SARS-CoV-2 variant. Omicron is known to induce milder lesions compared to the original Wuhan strain. Fatal infection of the Wuhan strain into the brain has been well documented in COVID-19 mouse models and human COVID-19 cases, but apparent infections into the brain by Omicron have not been reported in human adult cases or animal models. In this study, we investigated whether Omicron could spread to the brain using K18-hACE2 mice susceptible to SARS-CoV-2 infection. Results: K18-hACE2 mice were intranasally infected with 1 × 105 PFU of the original Wuhan strain and the Omicron variant of SARS-CoV-2. A follow-up was conducted 7 days post infection. All Wuhan-infected mice showed > 20% body weight loss, defined as the lethal condition, whereas two out of five Omicron-infected mice (40%) lost > 20% body weight. Histopathological analysis based on H&E staining revealed inflammatory responses in the brains of these two Omicron-infected mice. Immunostaining analysis of viral nucleocapsid protein revealed severe infection of neuron cells in the brains of these two Omicron-infected mice. Lymphoid depletion and apoptosis were observed in the spleen of Omicron-infected mice with brain infection. Conclusion Lethal conditions, such as severe body weight loss and encephalopathy, can occur in Omicron-infected K18-hACE2 mice. Our study reports, for the first time, that Omicron can induce brain infection with lymphoid depletion in the mouse COVID-19 model.

Purpose: Acute promyelocytic leukemia (APL) is a rare disease in children and there are some different characteristics between children and adult. We aimed to evaluate incidence, clinical characteristics and treatment outcomes of pediatric APL in Korea. Materials and Methods: Seventy-nine pediatric APL patients diagnosed from January 2009 to December 2016 in 16 tertiary medical centers in Korea were reviewed retrospectively. Results: Of 801 acute myeloid leukemia children, 79 (9.9%) were diagnosed with APL. The median age at diagnosis was 10.6 years (range, 1.3 to 18.0). Male and female ratio was 1:0.93. Thirty patients (38.0%) had white blood cell (WBC) count greater than 10×109/L at diagnosis. All patients received induction therapy consisting of all-trans retinoic acid and chemotherapy. Five patients (6.6%) died during induction chemotherapy and 66 patients (86.8%) achieved complete remission (CR) after induction chemotherapy. The causes of death were three intracranial hemorrhage, one cerebral infarction, and one sepsis. Five patients (7.1%) suffered a relapse during or after maintenance chemotherapy. The estimated 4-year event-free survival and overall survival (OS) rates were 82.1%±4.4%, 89.7%±5.1%, respectively. The 4-year OS was significantly higher in patients with initial WBC < 10×109/L than in those with initial WBC ≥ 10×109/L (p=0.020). Conclusion This study showed that the CR rates and survival outcomes in Korean pediatric APL patients were relatively good. The initial WBC count was the most important prognostic factor and most causes of death were related to serious bleeding in the early stage of treatment.

Objective: : The coronavirus disease 2019 (COVID-19) pandemic is affecting the characteristics of patients with head injuries. This study aimed to evaluate the effect of the COVID-19 pandemic on patients with head injuries at a regional emergency medical center in South Korea. Methods: : From April 2019 to November 2020, 350 patients with head injuries were admitted to our hospital. The study period was divided into the pre-COVID-19 (n=169) and COVID-19 (n=181) eras (10 months each). Patients with severe head injuries requiring surgery (n=74) were categorized into those who underwent surgery (n=41) and those who refused surgery (n=33). Results: : Head injuries in pediatric patients (<3 years) were more frequent in the COVID-19 era than in the pre-COVID-19 era (8.8% vs. 3.6%, p=0.048). More patients refused surgery in the COVID-19 era than in the pre-COVID-19 era (57.9% vs. 30.6%, p=0.021). Refusal of surgery was associated with old age (67.7±14.5 vs. 52.4±19.1, p<0.001), marital status (married, 84.8% vs. 61.0%, p=0.037), unemployment (42.4% vs. 68.3%, p=0.034), COVID-19 era (66.7% vs. 39.0%, p=0.021), and lower Glasgow coma scale scores (6.12±3.08 vs. 10.6±3.80, p<0.001). Multivariable logistic regression analysis revealed that refusal of surgery was independently associated with old age (adjusted odds ratio [OR], 1.084; 95% confidence interval [CI], 1.030–1.140; p=0.002), COVID-19 era (adjusted OR, 6.869; 95% CI, 1.624–29.054; p=0.009), and lower Glasgow coma scale scores (adjusted OR, 0.694; 95% CI, 0.568–0.848; p<0.001). Conclusion : We observed an increased prevalence of head injuries in pediatric patients (<3 years) during the COVID-19 pandemic. Additionally, among patients with severe head injuries requiring surgery, more patients refused to undergo surgery during the COVID-19 pandemic.