In recent years, next-generation sequencing (NGS)–based genetic testing has become crucial in cancer care. While its primary objective is to identify actionable genetic alterations to guide treatment decisions, its scope has broadened to encompass aiding in pathological diagnosis and exploring resistance mechanisms. With the ongoing expansion in NGS application and reliance, a compelling necessity arises for expert consensus on its application in solid cancers. To address this demand, the forthcoming recommendations not only provide pragmatic guidance for the clinical use of NGS but also systematically classify actionable genes based on specific cancer types. Additionally, these recommendations will incorporate expert perspectives on crucial biomarkers, ensuring informed decisions regarding circulating tumor DNA panel testing.

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.

In recent years, next-generation sequencing (NGS)–based genetic testing has become crucial in cancer care. While its primary objective is to identify actionable genetic alterations to guide treatment decisions, its scope has broadened to encompass aiding in pathological diagnosis and exploring resistance mechanisms. With the ongoing expansion in NGS application and reliance, a compelling necessity arises for expert consensus on its application in solid cancers. To address this demand, the forthcoming recommendations not only provide pragmatic guidance for the clinical use of NGS but also systematically classify actionable genes based on specific cancer types. Additionally, these recommendations will incorporate expert perspectives on crucial biomarkers, ensuring informed decisions regarding circulating tumor DNA panel testing.

Objective: The emergency department (ED) serves as the initial point of contact for many sepsis patients, but crowding can affect the timely delivery of essential interventions, such as antibiotics. This paper explores the relationship between antibiotics administration and ED crowding in the context of sepsis management. Methods: This single-center study at a tertiary care hospital included adult patients aged 18 and above who visited the emergency department from January 2018 to December 2022. Patients showing signs of septic shock upon arrival were selected as the study population. This study examined factors such as emergency department occupancy, antibiotic administration time, and their correlation with timely antibiotic treatment. Results: This study of 839 adult patients with septic shock found a weak correlation (P=0.107) between the time to antibiotic administration and department occupancy. Delayed antibiotic administration was observed when the occupancy exceeded 100%. On the other hand, there was no significant correlation between antibiotic administration within one hour and department occupancy. Conclusion Various factors, such as ED bed occupancy, medical staffing, resource allocation, and patient acuity, must be considered when comprehensively evaluating the impact of ED overcrowding on treating septic shock and other conditions.

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: 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.

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.

Objective: Microembolic infarcts are frequently observed on diffusion-weighted imaging (DWI) following endovascular treatment. We investigated DWI-positive lesions and symptomatic ischemic complications (SICs) in patients with ruptured and unruptured aneurysms following coiling and the relationship between DWI-positive lesions and antithrombotic drugs. Methods: Between January 2016 and December 2020, 83 patients underwent DWI within 48 h following endovascular treatment for ruptured (n=30) and unruptured (n=53) aneurysms. Results: The overall rate of DWI-positive lesions was 55.4%. There were no significant differences in the occurrence rate (45.3% vs. 43.3%, p=1.000) and the number of lesions (2.7±4.6 vs. 4.0±5.3, p=0.237) between unruptured and ruptured aneurysms. SIC occurred more frequently in patients with ruptured aneurysms than unruptured ones (20.0% vs. 1.9%, p=0.015). The cutoff value of DWI-positive lesions for predicting SIC was 5 (sensitivity 100%, specificity 78.9%). The procedure time was significantly longer in patients with DWI-positive lesions ≥5 than those with DWI-positive lesions <5 (104.1±43.8 vs. 85.1±30.8 min, p=0.030). Patients with DWI-positive lesions <5 were more frequently observed in the postprocedural heparinization group than in the no heparinization group (85.7% vs. 58.5%, p=0.012). Conclusions The incidence of DWI-positive lesions did not differ significantly between the ruptured and unruptured aneurysms. However, SIC occurred more frequently in patients with ruptured aneurysms. Longer procedure time is a risk factor for DWI-positive lesions, and postprocedural heparinization seems to reduce the incidence of DWI-positive lesions.