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: This study was performed to evaluate the efficacy and safety of lurasidone (160 mg/day) compared to quetiapine XR (QXR; 600 mg/day) in the treatment of acutely psychotic patients with schizophrenia. Methods: Patients were randomly assigned to 6 weeks of double-blind treatment with lurasidone 160 mg/day (n=105) or QXR 600 mg/day (n=105). Primary efficacy measure was the change from baseline to week 6 in Positive and Negative Syndrome Scale (PANSS) total score and Clinical Global Impressions severity (CGI-S) score. Adverse events, body measurements, and laboratory parameters were assessed. Results: Lurasidone demonstrated non-inferiority to QXR on the PANSS total score. Adjusted mean±standard error change at week 6 on the PANSS total score was -26.42±2.02 and -27.33±2.01 in the lurasidone and QXR group, respectively. The mean difference score was -0.91 (95% confidence interval -6.35–4.53). The lurasidone group showed a greater reduction in PANSS total and negative subscale on week 1 and a greater reduction in end-point CGI-S score compared to the QXR group. Body weight, body mass index, and waist circumference in the lurasidone group were reduced, with significantly lower mean change compared to QXR. Endpoint changes in glucose, cholesterol, triglycerides, and low-density lipoprotein levels were also significantly lower. The most common adverse drug reactions with lurasidone were akathisia and nausea. Conclusion Lurasidone 160 mg/day was found to be non-inferior to QXR 600 mg/day in the treatment of schizophrenia with comparable efficacy and tolerability. Adverse effects of lurasidone were generally tolerable, and beneficial effects on metabolic parameters can be expected.

Background: During the coronavirus disease 2019 (COVID-19) pandemic, there was a shortage of medical resources and the need for proper treatment guidelines for brain tumor patients became more pressing. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, has undertaken efforts to develop a guideline that is tailored to the domestic situation and that can be used in similar crisis situations in the future. As part II of the guideline, this consensus survey is to suggest management options in specific clinical scenarios during the crisis period. Methods: The KSNO Guideline Working Group consisted of 22 multidisciplinary experts on neuro-oncology in Korea. In order to confirm a consensus reached by the experts, opinions on 5 specific clinical scenarios about the management of brain tumor patients during the crisis period were devised and asked. To build-up the consensus process, Delphi method was employed. Results: The summary of the final consensus from each scenario are as follows. For patients with newly diagnosed astrocytoma with isocitrate dehydrogenase (IDH)-mutant and oligodendroglioma with IDH-mutant/1p19q codeleted, observation was preferred for patients with low-risk, World Health Organization (WHO) grade 2, and Karnofsky Performance Scale (KPS) ≥60, while adjuvant radiotherapy alone was preferred for patients with high-risk, WHO grade 2, and KPS ≥60. For newly diagnosed patients with glioblastoma, the most preferred adjuvant treatment strategy after surgery was radiotherapy plus temozolomide except for patients aged ≥70 years with KPS of 60 and unmethylated MGMT promoters. In patients with symptomatic brain metastasis, the preferred treatment differed according to the number of brain metastasis and performance status. For patients with newly diagnosed atypical meningioma, adjuvant radiation was deferred in patients with older age, poor performance status, complete resection, or low mitotic count. Conclusion It is imperative that proper medical care for brain tumor patients be sustained and provided, even during the crisis period. The findings of this consensus survey will be a useful reference in determining appropriate treatment options for brain tumor patients in the specific clinical scenarios covered by the survey during the future crisis.

Background: During the coronavirus disease 2019 (COVID-19) pandemic, the need for appropriate treatment guidelines for patients with brain tumors was indispensable due to the lack and limitations of medical resources. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, has undertaken efforts to develop a guideline that is tailored to the domestic situation and that can be used in similar crisis situations in the future. Methods: The KSNO Guideline Working Group was composed of 22 multidisciplinary experts on neuro-oncology in Korea. In order to reach consensus among the experts, the Delphi method was used to build up the final recommendations. Results: All participating experts completed the series of surveys, and the results of final survey were used to draft the current consensus recommendations. Priority levels of surgery and radiotherapy during crises were proposed using appropriate time window-based criteria for management outcome. The highest priority for surgery is assigned to patients who are life-threatening or have a risk of significant impact on a patient’s prognosis unless immediate intervention is given within 24–48 hours. As for the radiotherapy, patients who are at risk of compromising their overall survival or neurological status within 4–6 weeks are assigned to the highest priority. Curative-intent chemotherapy has the highest priority, followed by neoadjuvant/adjuvant and palliative chemotherapy during a crisis period. Telemedicine should be actively considered as a management tool for brain tumor patients during the mass infection crises such as the COVID-19 pandemic. Conclusion It is crucial that adequate medical care for patients with brain tumors is maintained and provided, even during times of crisis. This guideline will serve as a valuable resource, assisting in the delivery of treatment to brain tumor patients in the event of any future crisis.

Background: Three-dimensional (3D)-printed customized implants can be fabricated and utilized for all bones with massive bone defects. The main safety issues with 3D-printed implants made of Ti6Al4V alloy are related to the release of metal debris and residual powder. In this study, we investigated the perioperative titanium concentrations in whole blood and peri-implant fluid samples of patients who underwent limb salvage surgery with a 3D-printed Ti6Al4V implant. Methods: Nineteen patients who underwent limb salvage surgery with 3D-printed Ti6Al4V implants were divided into two groups:the serial samples group and the follow-up group. To observe metal distribution and clearance in the body, serial samples of blood and peri-implant fluid from the surgical drain were prospectively collected for five patients in the serial samples group. For the remaining 14 patients who were followed up for more than a year, blood samples were collected only once. Results: In the serial samples group, the mean baseline titanium concentration was 0.78 μg/L (range, 0.1–2.2 μg/L): 3 patients showed peak concentration before the third postoperative month, while 2 patients still showed an increasing pattern at this point.Total titanium mass in the surgical drain showed a wash-out phenomenon in a week, with a significant uniform decrease (p = 0.04).In 14 patients in the follow-up group, the mean titanium concentration in the whole blood was 10.8 μg/L (range, 0.3–36.6 μg/L). For the 14 patients with a long-term follow-up, the aluminum and vanadium concentrations were all negligible. Conclusions Whole blood titanium concentrations were higher after surgery using 3D-printed implants than after that using conventional orthopedic implants, but markedly lower than in patients with implant failure. None of the patients developed serious clinical adverse effects during follow-up.

Background: As the number of large-scale studies involving multiple organizations producing data has steadily increased, an integrated system for a common interoperable format is needed. In response to the coronavirus disease 2019 (COVID-19) pandemic, a number of global efforts are underway to develop vaccines and therapeutics. We are therefore observing an explosion in the proliferation of COVID-19 data, and interoperability is highly requested in multiple institutions participating simultaneously in COVID-19 pandemic research. Results: In this study, a laboratory information management system (LIMS) approach has been adopted to systemically manage various COVID-19 non-clinical trial data, including mortality, clinical signs, body weight, body temperature, organ weights, viral titer (viral replication and viral RNA), and multiorgan histopathology, from multiple institutions based on a web interface. The main aim of the implemented system is to integrate, standardize, and organize data collected from laboratories in multiple institutes for COVID-19 non-clinical efficacy testings. Six animal biosafety level 3 institutions proved the feasibility of our system. Substantial benefits were shown by maximizing collaborative high-quality non-clinical research. Conclusions This LIMS platform can be used for future outbreaks, leading to accelerated medical product development through the systematic management of extensive data from non-clinical animal studies.

Background/Aims: Recently, 1-L polyethylene glycol-ascorbic acid (PEG-Asc) has been used to reduce the volume of preparation agents in colonoscopy. This clinical trial aimed to compare the efficacy and safety of two types of 1-L PEG-Asc (CleanViewAL ® [Tae Joon Pharmaceutical Company, Seoul, Korea] and Plenvu ® [Norgine, Harefield, United Kingdom]) in average-aged adults. Methods: This study was a prospective, randomized, non-inferiority, open-label, phase 4 clinical trial. The primary endpoint was the efficacy evaluated using the Boston bowel preparation scale (BBPS), and the secondary endpoint was clinical safety. Results: In total, 173 patients were assigned to either the CleanViewAL ® (n=84) or Plenvu ® (n=89) group. Overall cleansing successes of 97.6% (82/84) and 98.8% (88/89) were achieved in the CleanViewAL ® group and in the Plenvu ® group, respectively, showing that CleanViewAL ® has similar bowel cleansing efficacy to Plenvu ® (95% CI, -0.052 to 0.027; p=0.207). The total BBPS score was 8.67±1.00 and 8.70±0.76 in the CleanViewAL ® group and Plenvu ® group, respectively (p=0.869). The most common adverse symptom was nausea, and no adverse symptoms requiring hospitalization were reported in either group. There were no cases of critical hypernatremia and liver dysfunction exceeding the common terminology criteria for adverse events grade I. An overall satisfaction score (scale of 1 to 10) showed no difference between the two groups (p=0.289). However, the CleanViewAL ® group showed a higher taste satisfaction score (scale of 1 to 5) than the Plenvu ® group (CleanViewAL ® : 2.90±0.91, Plenvu ® : 2.60±0.86, p=0.028). Conclusions Both types of 1-L PEG-Asc, CleanViewAL ® and Plenvu ® , are effective and safe bowel cleansing agents in average-aged adults. CleanViewAL ® was preferred in terms of taste satisfaction.

The Korean Society for Electrolyte and Blood Pressure Research, in collaboration with the Korean Society of Nephrology, has published a clinical practice guideline (CPG) document for hyponatremia treatment. The document is based on an extensive evidence-based review of the diagnosis, evaluation, and treatment of hyponatremia with the multidisciplinary participation of representative experts in hyponatremia with methodologist support for guideline development. This CPG consists of 12 recommendations (two for diagnosis, eight for treatment, and two for special situations) based on eight detailed topics and nine key questions. Each recommendation begins with statements graded by the strength of the recommendations and the quality of the evidence. Each statement is followed by rationale supporting the recommendations. The committee issued conditional recommendations in favor of rapid intermittent bolus administration of hypertonic saline in severe hyponatremia, the use of vasopressin receptor antagonists in heart failure with hypervolemic hyponatremia, and syndrome of inappropriate antidiuresis with moderate to severe hyponatremia, the individualization of desmopressin use, and strong recommendation on the administration of isotonic fluids as maintenance fluid therapy in hospitalized pediatric patients. We hope that this CPG will provide useful recommendations in practice, with the aim of providing clinical support for shared decision-making to improve patient outcomes.

The Korean Society for Electrolyte and Blood Pressure Research, in collaboration with the Korean Society of Nephrology, has published a clinical practice guideline (CPG) document for hyponatremia treatment. The document is based on an extensive evidence-based review of the diagnosis, evaluation, and treatment of hyponatremia with the multidisciplinary participation of representative experts in hyponatremia with methodologist support for guideline development. This CPG consists of 12 recommendations (two for diagnosis, eight for treatment, and two for special situations) based on eight detailed topics and nine key questions. Each recommendation begins with statements graded by the strength of the recommendations and the quality of the evidence. Each statement is followed by rationale supporting the recommendations. The committee issued conditional recommendations in favor of rapid intermittent bolus administration of hypertonic saline in severe hyponatremia, the use of vasopressin receptor antagonists in heart failure with hypervolemic hyponatremia, and syndrome of inappropriate antidiuresis with moderate to severe hyponatremia, the individualization of desmopressin use, and strong recommendation on the administration of isotonic fluids as maintenance fluid therapy in hospitalized pediatric patients. We hope that this CPG will provide useful recommendations in practice, with the aim of providing clinical support for shared decision-making to improve patient outcomes.

Background/Aims: The optimal treatment (Tx) for epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) patients with brain metastasis (BM) remains to be determined. Methods: A retrospective review was conducted on 77 NSCLC patients with synchronous BM who underwent first-line EGFR-tyrosine kinase inhibitor (TKI) Tx. The outcomes of patients were analyzed according to the clinicopathological characteristics including local Tx modalities. Results: Fifty-nine patients underwent local Tx for BM (gamma knife surgery [GKS], 37; whole brain radiotherapy [WBRT], 18; others, four) concurrently or sequentially with EGFR-TKI. Patients treated with TKI alone showed significantly lower incidence of central nervous system (CNS) symptoms. The median progression-free survival (PFS) and overall survival (OS) after the initiation of EGFR-TKI for all patients were 9 and 19 months, respectively. In 60 patients with follow-up brain imaging, the median time to CNS progression was 15 months. Patients with EGFR exon 19 deletion had a significantly longer median OS than those with other mutations including L858R (23 months vs. 17 months). Other clinical characteristics, including CNS symptoms, number of BM, and the use of local Tx were not associated with OS, as well as PFS. In terms of the local optimal Tx modality, no difference was found between GKS and WBRT in the OS and PFS. Conclusions This study suggests that EGFR-TKI may result in a favorable outcome in NSCLC patients with synchronous BM, especially in deletion 19 mutant, regardless of the extent of BM lesions or local Tx modalities. Patients with asymptomatic BM can be treated with EGFR-TKI and careful surveillance.