Background: Islet transplantation holds promise for treating selected type 1 diabetes mellitus patients, yet the scarcity of human donor organs impedes widespread adoption. Porcine islets, deemed a viable alternative, recently demonstrated successful longterm survival without zoonotic risks in a clinically relevant pig-to-non-human primate islet transplantation model. This success prompted the development of a clinical trial protocol for porcine islet xenotransplantation in humans. Methods: A single-center, open-label clinical trial initiated by the sponsor will assess the safety and efficacy of porcine islet transplantation for diabetes patients at Gachon Hospital. The protocol received approval from the Gachon Hospital Institutional Review Board (IRB) and the Korean Ministry of Food and Drug Safety (MFDS) under the Investigational New Drug (IND) process. Two diabetic patients, experiencing inadequate glycemic control despite intensive insulin treatment and frequent hypoglycemic unawareness, will be enrolled. Participants and their family members will engage in deliberation before xenotransplantation during the screening period. Each patient will receive islets isolated from designated pathogen-free pigs. Immunosuppressants and systemic infection prophylaxis will follow the program schedule. The primary endpoint is to confirm the safety of porcine islets in patients, and the secondary endpoint is to assess whether porcine islets can reduce insulin dose and the frequency of hypoglycemic unawareness. Conclusion A clinical trial protocol adhering to global consensus guidelines for porcine islet xenotransplantation is presented, facilitating streamlined implementation of comparable human trials worldwide.

Purpose: This study examined the characteristics and outcomes of resective epilepsy surgery following corpus callosotomy (CC) in children with Lennox-Gastaut syndrome (LGS). Methods: We retrospectively analyzed 17 children with LGS who underwent resective surgery (RS) after CC over a span of 10 years, with a minimum of 2 years of follow-up, at a single tertiary epilepsy center in Korea. Results: Of the 17 patients, 13 (73.5%) demonstrated favorable surgical outcomes (Engel class I or II) at 1 year after RS, and eight (47.1%) were ultimately free of seizures 2 years after surgery. A significantly larger decrease in the number of anti-seizure medications taken from before to 2 years after the final surgical procedure was observed in the group that became seizure-free than in the group with persistent seizures (P=0.062). Furthermore, a significantly greater decline in daily adaptive function was found in the persistent seizure group (P=0.059). The baseline characteristics, results of presurgical evaluation, and treatment-related factors assessed prior to surgery showed no significant differences between the seizure-free group and the group with persistent seizures. Conclusion In conclusion, RS may be a viable option for patients with LGS who exhibit lateralization and/or localization on presurgical evaluation after CC, as the procedure may reveal a concealed primary focus. The proactive implementation of two-stage epilepsy surgery could provide significant seizure reduction and preservation of cognitive function in carefully selected patients with LGS.

Background: Islet transplantation holds promise for treating selected type 1 diabetes mellitus patients, yet the scarcity of human donor organs impedes widespread adoption. Porcine islets, deemed a viable alternative, recently demonstrated successful longterm survival without zoonotic risks in a clinically relevant pig-to-non-human primate islet transplantation model. This success prompted the development of a clinical trial protocol for porcine islet xenotransplantation in humans. Methods: A single-center, open-label clinical trial initiated by the sponsor will assess the safety and efficacy of porcine islet transplantation for diabetes patients at Gachon Hospital. The protocol received approval from the Gachon Hospital Institutional Review Board (IRB) and the Korean Ministry of Food and Drug Safety (MFDS) under the Investigational New Drug (IND) process. Two diabetic patients, experiencing inadequate glycemic control despite intensive insulin treatment and frequent hypoglycemic unawareness, will be enrolled. Participants and their family members will engage in deliberation before xenotransplantation during the screening period. Each patient will receive islets isolated from designated pathogen-free pigs. Immunosuppressants and systemic infection prophylaxis will follow the program schedule. The primary endpoint is to confirm the safety of porcine islets in patients, and the secondary endpoint is to assess whether porcine islets can reduce insulin dose and the frequency of hypoglycemic unawareness. Conclusion A clinical trial protocol adhering to global consensus guidelines for porcine islet xenotransplantation is presented, facilitating streamlined implementation of comparable human trials worldwide.

Background: Islet transplantation holds promise for treating selected type 1 diabetes mellitus patients, yet the scarcity of human donor organs impedes widespread adoption. Porcine islets, deemed a viable alternative, recently demonstrated successful longterm survival without zoonotic risks in a clinically relevant pig-to-non-human primate islet transplantation model. This success prompted the development of a clinical trial protocol for porcine islet xenotransplantation in humans. Methods: A single-center, open-label clinical trial initiated by the sponsor will assess the safety and efficacy of porcine islet transplantation for diabetes patients at Gachon Hospital. The protocol received approval from the Gachon Hospital Institutional Review Board (IRB) and the Korean Ministry of Food and Drug Safety (MFDS) under the Investigational New Drug (IND) process. Two diabetic patients, experiencing inadequate glycemic control despite intensive insulin treatment and frequent hypoglycemic unawareness, will be enrolled. Participants and their family members will engage in deliberation before xenotransplantation during the screening period. Each patient will receive islets isolated from designated pathogen-free pigs. Immunosuppressants and systemic infection prophylaxis will follow the program schedule. The primary endpoint is to confirm the safety of porcine islets in patients, and the secondary endpoint is to assess whether porcine islets can reduce insulin dose and the frequency of hypoglycemic unawareness. Conclusion A clinical trial protocol adhering to global consensus guidelines for porcine islet xenotransplantation is presented, facilitating streamlined implementation of comparable human trials worldwide.

Background: Islet transplantation holds promise for treating selected type 1 diabetes mellitus patients, yet the scarcity of human donor organs impedes widespread adoption. Porcine islets, deemed a viable alternative, recently demonstrated successful longterm survival without zoonotic risks in a clinically relevant pig-to-non-human primate islet transplantation model. This success prompted the development of a clinical trial protocol for porcine islet xenotransplantation in humans. Methods: A single-center, open-label clinical trial initiated by the sponsor will assess the safety and efficacy of porcine islet transplantation for diabetes patients at Gachon Hospital. The protocol received approval from the Gachon Hospital Institutional Review Board (IRB) and the Korean Ministry of Food and Drug Safety (MFDS) under the Investigational New Drug (IND) process. Two diabetic patients, experiencing inadequate glycemic control despite intensive insulin treatment and frequent hypoglycemic unawareness, will be enrolled. Participants and their family members will engage in deliberation before xenotransplantation during the screening period. Each patient will receive islets isolated from designated pathogen-free pigs. Immunosuppressants and systemic infection prophylaxis will follow the program schedule. The primary endpoint is to confirm the safety of porcine islets in patients, and the secondary endpoint is to assess whether porcine islets can reduce insulin dose and the frequency of hypoglycemic unawareness. Conclusion A clinical trial protocol adhering to global consensus guidelines for porcine islet xenotransplantation is presented, facilitating streamlined implementation of comparable human trials worldwide.

Background: Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator- activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined. Methods: This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months. Conclusion This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D.

Purpose: The benefit of adjuvant chemotherapy following curative-intent surgery in pancreatic ductal adenocarcinoma (PDAC) patients who had received neoadjuvant FOLFIRINOX is unclear. This study aimed to assess the survival benefit of adjuvant chemotherapy in this patient population. Materials and Methods: This retrospective study included 218 patients with localized non-metastatic PDAC who received neoadjuvant FOLFIRINOX and underwent curative-intent surgery (R0 or R1) between January 2017 and December 2020. The association of adjuvant chemotherapy with disease-free survival (DFS) and overall survival (OS) was evaluated in overall patients and in the propensity score matched (PSM) cohort. Subgroup analysis was conducted according to the pathology-proven lymph node status. Results: Adjuvant chemotherapy was administered to 149 patients (68.3%). In the overall cohort, the adjuvant chemotherapy group had significantly improved DFS and OS compared to the observation group (DFS: median, 13.8 months [95% confidence interval (CI), 11.0 to 19.1] vs. 8.2 months [95% CI, 6.5 to 12.0]; p < 0.001; and OS: median, 38.0 months [95% CI, 32.2 to not assessable] vs. 25.7 months [95% CI, 18.3 to not assessable]; p=0.005). In the PSM cohort of 57 matched pairs of patients, DFS and OS were better in the adjuvant chemotherapy group than in the observation group (p < 0.001 and p=0.038, respectively). In the multivariate analysis, adjuvant chemotherapy was a significant favorable prognostic factor (vs. observation; DFS: hazard ratio [HR], 0.51 [95% CI, 0.36 to 0.71; p < 0.001]; OS: HR, 0.45 [95% CI, 0.29 to 0.71; p < 0.001]). Conclusion Among PDAC patients who underwent surgery following neoadjuvant FOLFIRINOX, adjuvant chemotherapy may be associated with improved survival. Randomized studies should be conducted to validate this finding.

Purpose: Universal screening for Lynch syndrome (LS) refers to routine tumor testing for microsatellite instability (MSI) among all patients with colorectal cancer (CRC). Despite its widespread adoption, real-world data on the yield is lacking in Korean population. We studied the yield of adopting universal screening for LS in comparison with pedigree-based screening in a tertiary center. Materials and Methods: CRC patients from 2007-2018 were reviewed. Family histories were obtained and were evaluated for hereditary nonpolyposis colorectal cancer (HNPCC) using Amsterdam II criteria. Tumor testing for MSI began in 2007 and genetic testing was offered using all available clinicopathologic data. Yield of genetic testing for LS was compared for each approach and step. Results: Of the 5,520 patients, tumor testing was performed in 4,701 patients (85.2%) and family histories were obtained from 4,241 patients (76.8%). Hereditary CRC (LS or HNPCC) was present in 69 patients (1.3%). MSI-high was present in 6.9%, and 25 patients had confirmed LS. Genetic testing was performed in 41.2% (47/114) of MSI-high patients, out of which 40.4% (19/47) were diagnosed with LS. There were six additional LS patients found outside of tumor testing. For pedigree-based screening, Amsterdam II criteria diagnosed 55 patients with HNPCC. Fifteen of these patients underwent genetic testing, and 11 (73.3%) were diagnosed with LS. Two patients without prior family history were diagnosed with LS and relied solely on tumor testing results. Conclusion Despite widespread adoption of routine tumor testing for MSI, this is not a fail-safe approach to screen all LS patients. Obtaining a thorough family history in combination with universal screening provides a more comprehensive ‘universal’ screening method for LS.

Background: This study aimed to evaluate whether fluvoxamine reduces clinical deterioration in adult patients with mild to moderate coronavirus disease 2019 (COVID-19), and to identify risk factors for clinical deterioration in patients admitted to a community treatment center (CTC). Materials and Methods: A randomized, placebo-controlled trial was conducted in a CTC, in Seoul, Korea from January 15, 2021, to February 19, 2021. Symptomatic adult patients with positive results of severe acute respiratory syndrome coronavirus 2 real timepolymerase chain reaction within 3 days of randomization were assigned at random to receive 100 mg of fluvoxamine or placebo twice daily for 10 days. The primary outcome was clinical deterioration defined by any of the following criteria: oxygen requirement to keep oxygen saturation over 94.0%, aggravation of pneumonia with dyspnea, or World Health Organization clinical progression scale 4 or greater. Results: Of 52 randomized participants [median (interquartile range) age, 53.5 (43.3 - 60.0) years; 31 (60.0%) men], 44 (85.0%) completed the trial. Clinical deterioration occurred in 2 of 26 patients in each group (P >0.99). There were no serious adverse events in either group. Clinical deterioration occurred in 15 (6.0%) of 271 patients admitted to the CTC, and all of them were transferred to a hospital. In multivariate analysis, age between 55 and 64, fever and pneumonia at admission were independent risk factors for clinical deterioration. Conclusion In this study of adult patients with symptomatic COVID-19 who were admitted to the CTC, there was no significant differences in clinical deterioration between patients treated with fluvoxamine and placebo (ClinicalTrials.gov Identifier: NCT04711863).