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.

Background: and Purpose There is extensive literature on monogenic epilepsies caused by mutations in familiar channelopathy genes such as SCN1A. However, information on other lesscommon channelopathy genes is scarce. This study aimed to explore the genetic and clinical characteristics of patients diagnosed with unusual voltage-gated sodium and potassium channelopathies related to epilepsy. Methods: This observational, retrospective study analyzed pediatric patients with epilepsy who carried pathogenic variants of unusual voltage-gated sodium and potassium channelopathy genes responsible for seizure-associated phenotypes. Targeted next-generation sequencing (NGS) panel tests were performed between November 2016 and June 2022 at Severance Children’s Hospital, Seoul, South Korea. Clinical characteristics and the treatment responses to different types of antiseizure medications were further analyzed according to different types of gene mutation. Results: This study included 15 patients with the following unusual voltage-gated sodium and potassium channelopathy genes: SCN3A (n=1), SCN4A (n=1), KCNA1 (n=1), KCNA2 (n=4), KCNB1 (n=6), KCNC1 (n=1), and KCNMA1 (n=1). NGS-based genetic testing identified 13 missense mutations (87%), 1 splice-site variant (7%), and 1 copy-number variant (7%). Developmental and epileptic encephalopathy was diagnosed in nine (60%) patients. Seizure freedom was eventually achieved in eight (53%) patients, whereas seizures persisted in seven (47%) patients. Conclusions Our findings broaden the genotypic and phenotypic spectra of less-common voltage-gated sodium and potassium channelopathies associated with epilepsy.

Background: The obesity epidemic is associated with the emergence of new kidney diseases including obesity-related glomerulopathy (ORG) and metabolic syndrome-associated disorders. However, the effects of obesity on prevalence and outcome of biopsy-proven kidney disease are not well known. Methods: We analyzed 14,492 kidney biopsies in 18 hospitals from 1979 to 2018 in Korea.Obesity was defined as a body mass index value of ≥ 30 kg/m 2 . Results: The most common disease was IgA nephropathy (IgAN) in both obese and nonobese participants (33.7% vs. 38.9%). Obesity was associated with a higher risk of focal segmental glomerulosclerosis (FSGS) and hypertensive nephropathy (HT-N) (odds ratio [OR], 1.72, 95% confidence interval [CI], 1.37–2.17; OR, 1.96, 95% CI, 1.21–3.19) and a lower risk of IgAN (OR, 0.74, 95% CI, 0.62–0.88). During the median follow up of 93.1 ± 88.7 months, obesity increased the risk of end-stage kidney disease (ESKD) in patients with IgAN (relative risk [RR], 1.49, 95% CI, 1.01–2.20) and lupus nephritis (LN) (RR, 3.43, 95% CI, 1.36–8.67). Of 947 obese individuals, ORG was detected in 298 (31.5%), and 230 participants had other kidney diseases, most commonly, IgAN (40.9%) followed by diabetic nephropathy (15.2%). Participants with ORG, when combined with other renal diseases, showed higher risks for developing ESKD compared to those with ORG alone (RR, 2.48, 95% CI, 1.09–5.64). Conclusion Obesity is associated with an increased risk of FSGS and HT-N, and also increase the ESKD risk in IgAN and LN patients. ORG in obese participants may have favorable renal outcomes if it occurs alone without any other renal disease.

Background/Aims: Hypertension is considered a risk factor in immunoglobulin A nephropathy (IgAN). However, after IgAN diagnosis, the relationship between early blood pressure control and renal prognosis remains unclear. This study aimed to analyze the association between the prognosis of IgAN patients and a controlled status of hypertension within the first year of IgAN diagnosis. Methods: We retrospectively analyzed 2,945 patients diagnosed with IgAN by renal biopsy. The patients were divided into ‘normal,’ ‘new-onset,’ ‘well-controlled,’ and ‘poorly-controlled’ groups using blood pressure data from two consecutive measurements performed within a year. The Kaplan-Meier survival analysis and Cox proportional-hazards regression model were used to survey the independent association between recovery from hypertension and the risk of IgAN progression. The primary endpoint was IgAN progression defined as the initiation of dialysis or kidney transplantation. Results: Before IgAN diagnosis, 1,239 patients (42.1%) had been diagnosed with hypertension. In the fully adjusted Cox proportional-hazards models, the risk of IgAN progression increased by approximately 1.7-fold for the prevalence of hypertension. In the subgroup analyses, the ‘well-controlled’ group showed a statistically significant risk of IgAN progression (hazard ratio [HR], 3.19; 95% confidence interval [CI], 1.103 to 9.245; p = 0.032). Moreover, the ‘new-onset’ and ‘poorly-controlled’ groups had an increased risk of IgAN progression compared to the ‘normal’ group (HR, 2.58; 95% CI, 1.016 to 6.545; p = 0.046 and HR, 3.85;95% CI, 1.541 to 9.603; p = 0.004, respectively). Conclusions Although hypertension was well-controlled in the first year after IgAN diagnosis, it remained a risk factor for IgAN progression.

Purpose: Colorectal cancer (CRC) occurs in all age groups, and the application of treatment may vary according to age. The study was designed to identify the characteristics of CRC by age. Methods: A total of 4,326 patients undergoing primary resection for CRC from September 2006 to July 2019 were reviewed. Patient and tumor characteristics, operative and postoperative data, and oncologic outcome were compared Results: Patients aged 60 to 69 years comprised the largest age group (29.7%), followed by those aged 50 to 59 and 70 to 79 (24.5% and 23.9%, respectively). Rectal cancer was common in all age groups, but right-sided colon cancer tended to be more frequent in older patients. In very elderly patients, there were significant numbers of emergency surgeries, and the frequencies of open surgery and permanent stoma were greater. In contrast, total abdominal colectomy or total proctocolectomy was performed frequently in patients in their teens and twenties. The elderly patients showed more advanced tumor stages and postoperative ileus. The incidence of adjuvant treatment was low in elderly patients, who also had shorter follow-up periods. Overall survival was reduced in older patients with stages 0 to 3 CRC (P<0.001), but disease-free survival did not differ by age (P=0.391). Conclusion CRC screening at an earlier age than is currently undertaken may be necessary in Korea. In addition, improved surgical and oncological outcomes can be achieved through active treatment of the growing number of elderly CRC patients.

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: The endoscopic step-up approach is accepted as the preferred treatment for complicated or symptomatic walled-off necrosis (WON). Direct endoscopic necrosectomy (DEN) is an effective therapeutic option, but few reports describe long-term follow-up in this patient population. Thus, we aim to assess the long-term outcomes of DEN following severe necrotizing pancreatitis. Methods: The data of all acute pancreatitis patients who underwent DEN following endoscopic transmural drainage from six referral centers between 2007 and 2017 were retrospectively collected. Results: Sixty patients (76.7% male, mean age 48.3 years) underwent a median of 4 sessions of DEN starting at a median of 45.5 days after the onset of acute pancreatitis. Clinical success was achieved in 51 patients (85%), with a 35% complication rate and a 5% mortality rate. Using multivariate analysis, the risk factor associated with DEN failure or major DEN complications requiring intervention or surgery was an identified bacterial/fungal WON infection (odds ratio, 19.3; 95% confidence interval, 1.5 to 261.7). During the median follow-up period of 27 months, complicated WON recurrence was observed in 5.3% of patients, and long-term complications occurred in 24.6% of patients (four exocrine insufficiency, nine newly developed diabetes mellitus, one recurrent small bowel obstruction, one chylous ascites). Conclusions Considering that long-term complications are similar to those observed after pancreatectomy, DEN should be performed meticulously while minimizing damage to the viable pancreatic parenchyma with adequate antibiotic escalation.