Objective: We evaluated the pharmacokinetics, tissue concentrations, and toxicities of belotecan during rotational intraperitoneal pressurized aerosol chemotherapy (RIPAC) in pigs. Methods: We sprayed belotecan in 10% and 30% of doses for intravenous chemotherapy in six pigs (cohort 1, n=3, 0.50 mg/m2 ; cohort 2, n=3, 1.5 mg/m2 ). We evaluated the time-dependent plasma concentrations of belotecan before RIPAC to 120 hours for the pharmacokinetics, tissue concentrations in twelve peritoneal regions, and hepatic and renal functions before RIPAC to 120 hours in the 2 cohorts. Results: Mean values of the peak plasma concentration (Cmax ), the time to Cmax , the time taken for Cmax to drop in half, and the area under the curve from time zero to the time of last quantifiable concentration were 905 and 3,700 ng/mL, 1.42 and 1.50 hours, 3.64 and 5.60 hours, and 2,260 and 17,900 pg·hr/mL in cohorts 1 and 2, respectively. Mean values of tissue concentrations were 1.5 to 15.3 times higher in cohort 1 than in cohort 2 despite the similar ratio of tissue to plasma concentration, and tissue concentrations in the two cohorts were higher in the parietal peritoneum than in the visceral peritoneum. However, hepatic and renal functions were not different before RIPAC to 120 hours in the two cohorts. Conclusion RIPAC using belotecan of 0.5 mg/m2 and 1.5 mg/m2 may be feasible with fewer hepatic and renal toxicities in pigs. Thus, belotecan of 1.5 mg/m2 may be considered as the starting dose for RIPAC in a phase 1 trial.

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: There is increasing evidence that probiotics are effective in treating allergic rhinitis (AR), while some controversies remain. This study was performed to evaluate the therapeutic effect and safety of a mixture of Bifidobacterium longum and Lactobacillus plantarum (NVP-1703) in children with AR. Methods: In a randomized, double-blind, placebo-controlled study, children aged 6 to 19 years with perennial AR were treated with NVP-1703 at a dose of 1 × 1010 CFU/day or placebo once a day for 4 weeks. Total nasal symptom score (TNSS), nasal symptom duration score (NSDS), quality of life (QoL), allergic inflammatory markers, and safety parameters were evaluated. Results: After 4 weeks of treatment, the TNSS in the NVP-1703 group significantly decreased compared to that in the placebo group (P = 0.011), both in the morning and the evening (P = 0.031 and P = 0.004, respectively). The NSDS also significantly decreased in the NVP-1703 group compared to that in the placebo group (P = 0.018). QoL scores, particularly those related to mouth breathing and itchy nose, showed a significant improvement in the NVP-1703 group compared to the placebo group. The ratios of interleukin (IL)-4/IL-22 and IL-5/IL-22 were significantly reduced in the NVP-1703 group after the treatment compared to the baseline values. No notable adverse events were reported in the NVP-1703 group. Conclusion Oral administration of a mixture of B. longum and L. plantarum (NVP-1703) improved both AR symptoms and QoL in children with perennial AR, accompanied by decreases in the ratios of T helper 2 cytokines to IL-22.

Background: There is increasing evidence that probiotics are effective in treating allergic rhinitis (AR), while some controversies remain. This study was performed to evaluate the therapeutic effect and safety of a mixture of Bifidobacterium longum and Lactobacillus plantarum (NVP-1703) in children with AR. Methods: In a randomized, double-blind, placebo-controlled study, children aged 6 to 19 years with perennial AR were treated with NVP-1703 at a dose of 1 × 1010 CFU/day or placebo once a day for 4 weeks. Total nasal symptom score (TNSS), nasal symptom duration score (NSDS), quality of life (QoL), allergic inflammatory markers, and safety parameters were evaluated. Results: After 4 weeks of treatment, the TNSS in the NVP-1703 group significantly decreased compared to that in the placebo group (P = 0.011), both in the morning and the evening (P = 0.031 and P = 0.004, respectively). The NSDS also significantly decreased in the NVP-1703 group compared to that in the placebo group (P = 0.018). QoL scores, particularly those related to mouth breathing and itchy nose, showed a significant improvement in the NVP-1703 group compared to the placebo group. The ratios of interleukin (IL)-4/IL-22 and IL-5/IL-22 were significantly reduced in the NVP-1703 group after the treatment compared to the baseline values. No notable adverse events were reported in the NVP-1703 group. Conclusion Oral administration of a mixture of B. longum and L. plantarum (NVP-1703) improved both AR symptoms and QoL in children with perennial AR, accompanied by decreases in the ratios of T helper 2 cytokines to IL-22.

Background: There is increasing evidence that probiotics are effective in treating allergic rhinitis (AR), while some controversies remain. This study was performed to evaluate the therapeutic effect and safety of a mixture of Bifidobacterium longum and Lactobacillus plantarum (NVP-1703) in children with AR. Methods: In a randomized, double-blind, placebo-controlled study, children aged 6 to 19 years with perennial AR were treated with NVP-1703 at a dose of 1 × 1010 CFU/day or placebo once a day for 4 weeks. Total nasal symptom score (TNSS), nasal symptom duration score (NSDS), quality of life (QoL), allergic inflammatory markers, and safety parameters were evaluated. Results: After 4 weeks of treatment, the TNSS in the NVP-1703 group significantly decreased compared to that in the placebo group (P = 0.011), both in the morning and the evening (P = 0.031 and P = 0.004, respectively). The NSDS also significantly decreased in the NVP-1703 group compared to that in the placebo group (P = 0.018). QoL scores, particularly those related to mouth breathing and itchy nose, showed a significant improvement in the NVP-1703 group compared to the placebo group. The ratios of interleukin (IL)-4/IL-22 and IL-5/IL-22 were significantly reduced in the NVP-1703 group after the treatment compared to the baseline values. No notable adverse events were reported in the NVP-1703 group. Conclusion Oral administration of a mixture of B. longum and L. plantarum (NVP-1703) improved both AR symptoms and QoL in children with perennial AR, accompanied by decreases in the ratios of T helper 2 cytokines to IL-22.

Background: There is increasing evidence that probiotics are effective in treating allergic rhinitis (AR), while some controversies remain. This study was performed to evaluate the therapeutic effect and safety of a mixture of Bifidobacterium longum and Lactobacillus plantarum (NVP-1703) in children with AR. Methods: In a randomized, double-blind, placebo-controlled study, children aged 6 to 19 years with perennial AR were treated with NVP-1703 at a dose of 1 × 1010 CFU/day or placebo once a day for 4 weeks. Total nasal symptom score (TNSS), nasal symptom duration score (NSDS), quality of life (QoL), allergic inflammatory markers, and safety parameters were evaluated. Results: After 4 weeks of treatment, the TNSS in the NVP-1703 group significantly decreased compared to that in the placebo group (P = 0.011), both in the morning and the evening (P = 0.031 and P = 0.004, respectively). The NSDS also significantly decreased in the NVP-1703 group compared to that in the placebo group (P = 0.018). QoL scores, particularly those related to mouth breathing and itchy nose, showed a significant improvement in the NVP-1703 group compared to the placebo group. The ratios of interleukin (IL)-4/IL-22 and IL-5/IL-22 were significantly reduced in the NVP-1703 group after the treatment compared to the baseline values. No notable adverse events were reported in the NVP-1703 group. Conclusion Oral administration of a mixture of B. longum and L. plantarum (NVP-1703) improved both AR symptoms and QoL in children with perennial AR, accompanied by decreases in the ratios of T helper 2 cytokines to IL-22.

Objective: The cutaneous manifestation of decompression sickness (DCS) known as cutis marmorata (CM) is generally mild, but it is often accompanied by severe DCS or may be a prognostic sign. We aimed to analyze the clinical course of patients with CM to improve our understanding of CM. Methods: From January 2016 to December 2020, a retrospective cohort single-center study was conducted on patients with acute DCS who underwent emergency recompression therapy. We analyzed their data and the clinical outcomes after recompression therapy. In addition, we reviewed relevant literature. Results: A total of 341 people were enrolled during the study period. Of them 94 (27.6%) patients presented with CM and the symptoms appeared at an average of about 60.5 minutes after surfacing. Among the CM patients, 76.6% had accompanying DCS type II, and in 23.4%, had accompanying DCS type I (P=0.011). With single recompression therapy, 88.3% of patients with CM immediately recovered. Among these 95.4% of patients with DCS type I and 86.1% with DCS type II recovered immediately. However, there were no statistical differences in the immediate treatment outcomes according to the delay time from the onset of symptoms to recompression therapy, accompanying symptomatic DCS classification, and recompression modalities. Ultimately, all the patients recovered from CM. Conclusion CM by itself can be considered a mild DCS in terms of treatment progress, but prompt treatment is required to prevent complications. In addition, greater focus is needed on other accompanying DCS symptoms in patients with CM, and the treatment method should be determined accordingly.

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.