Purpose: GC1118 is a novel antibody targeting epidermal growth factor receptor (EGFR) with enhanced blocking activity against both low- and high-affinity EGFR ligands. A phase 1b/2a study was conducted to determine a recommended phase 2 dose (RP2D) of GC1118 in combination with 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) (phase 1b) and to assess the safety and efficacy of GC1118 plus FOLFIRI as a second-line therapy for recurrent/metastatic colorectal cancer (CRC) (phase 2a). Materials and Methods: Phase 1b was designed as a standard 3+3 dose-escalation study with a starting dose of GC1118 (3 mg/kg/week) in combination with biweekly FOLFIRI (irinotecan 180 mg/m2; leucovorin 400 mg/m2; 5-fluorouracil 400 mg/m2 bolus and 2,400 mg/m2 infusion over 46 hours) in patients with solid tumors refractory to standard treatments. The subsequent phase 2a part was conducted with objective response rate (ORR) as a primary endpoint. Patients with KRAS/NRAS/BRAF wild-type, EGFR-positive, recurrent/metastatic CRC resistant to the first-line treatment were enrolled in the phase 2a study. Results: RP2D of GC1118 was determined to be 3 mg/kg/wk in the phase 1b study (n=7). Common adverse drug reactions (ADRs) observed in the phase 2a study (n=24) were acneiform rash (95.8%), dry skin (66.7%), paronychia (58.3%), and stomatitis (50.0%). The most common ADR of ≥ grade 3 was neutropenia (33.3%). ORR was 42.5% (95% confidence interval [CI], 23.5 to 62.0), and median progression-free survival was 6.7 months (95% CI, 4.0-8.0). Conclusion GC1118 administered weekly at 3 mg/kg in combination with FOLFIRI appears as an effective and safe treatment option in recurrent/metastatic CRC.

The coronavirus disease (COVID-19) pandemic has transformed clinical practice and health systems. This paper provides an overview of COVID-19 clinical management and health-care pathway challenges that the World Health Organization and its Member States in the Western Pacific Region have faced. The experiences and lessons identified can help countries to better prepare for future pandemics.

Objective: Glucagon in mammals and its homolog (adipokinetic hormone [AKH] in Drosophila melanogaster) are peptide hormones which regulate lipid metabolism by breaking down triglycerides. Although regulatory mechanisms of glucagon and Akh expression have been widely studied, post-transcriptional gene expression of glucagon has not been investigated thoroughly. In this study, we aimed to profile proteins binding with Gcg messenger RNA (mRNA) in mouse and Akh mRNA in Drosophila. Methods: Drosophila Schneider 2 (S2) and mouse 3T3-L1 cell lysates were utilized for affinity pull down of Akh and Gcg mRNA respectively using biotinylated anti-sense DNA oligoes against target mRNAs. Mass spectrometry and computational network analysis revealed mRNA-interacting proteins residing in functional proximity. Results: We observed that 1) 91 proteins interact with Akh mRNA from S2 cell lysates, 2) 34 proteins interact with Gcg mRNA from 3T3-L1 cell lysates. 3) Akh mRNA interactome revealed clusters of ribosomes and known RNA-binding proteins (RBPs). 4) Gcg mRNA interactome revealed mRNA-binding proteins including Plekha7, zinc finger protein, carboxylase, lipase, histone proteins and a cytochrome, Cyp2c44. 5) Levels of Gcg mRNA and its interacting proteins are elevated in skeletal muscles isolated from old mice compared to ones from young mice. Conclusion Akh mRNA in S2 cells are under active translation in a complex of RBPs and ribosomes. Gcg mRNA in mouse precursor adipocyte is in a condition distinct from Akh mRNA due to biochemical interactions with a subset of RBPs and histones. We anticipate that our study contributes to investigating regulatory mechanisms of Gcg and Akh mRNA decay, translation, and localization.

Background: Prurigo nodularis (PN) is a chronic pruritic skin disorder with a large number of hyperkeratotic nodules. The precise mechanisms of its pathogenesis remain unknown. PN has been linked to atopic dermatitis (AD), but its association remains unclear. Objective: We aimed to investigate the clinical, histological, and immunohistochemical characteristics of patients with PN and PN underlying AD (PN-AD). Methods: Eight patients were recruited for PN, PN-AD, and eight normal subjects, respectively. Skin tissues were obtained from patients and healthy subjects for histological and immunohistochemical analyses. Results: Histological examination showed increased epidermal thickness and dermal inflammatory cell counts in the PN-AD and PN groups compared to normal subjects. Immunohistochemical analyses revealed that the expression of interleukin (IL)-4, IL-13, IL-18, IL-31, IL-33, interferon (IFN)-γ, stromal-derived factor (SDF) 1-α and thymic stromal lymphopoietin (TSLP) was increased in the tissues of PN-AD and PN groups, in which the staining intensities of IL-4, IL-13, SDF1-α and TSLP in the PN-AD group were higher than those in the PN group, but the differences were not statistically significant. Conversely, the staining intensities of IL-18, IL-33 and IFN-γ were significantly higher in the PN group than those in the PN-AD group. Conclusion The pathogenesis of PN may differ from that of PN-AD, in which IL-18, IL-33 and IFN-γ may be associated, implying that epidermal injury is the initial cause of IL-18 and IL-33 induction, which then increases IFN-γ, resulting in the inflammatory process of PN.

Objective: This study aimed to overview and assess the effectiveness of the policies and regulations that have governed new drug access in Korea, and to propose policies to enhance patient access to drugs, particularly for new innovative medicines. Methods: We approached drug access issues in two perspectives: approval lag (or availability) and reimbursement lag (or affordability). The issues were identified and evaluated through the review of literature, public documents, reports published by the government agencies and private organizations, and news articles. Results: To shorten approval lag, it is recommended to hire and train more reviewers at the Ministry of Food and Drug Safety. Increasing user fees to a realistic level can facilitate this process. To reduce reimbursement lag, flexible incremental cost-effectiveness ratio threshold, alternative cost-effectiveness evaluation, and establishment of funding source other than the national health insurance are identified as the areas to be improved. Conclusion The current policies and regulations had to be supplemented by new systems to drastically promote patient accessibility to new drugs, consequently in order to promote national public health.

Objective: This study aimed to overview and assess the effectiveness of the policies and regulations that have governed new drug access in Korea, and to propose policies to enhance patient access to drugs, particularly for new innovative medicines. Methods: We approached drug access issues in two perspectives: approval lag (or availability) and reimbursement lag (or affordability). The issues were identified and evaluated through the review of literature, public documents, reports published by the government agencies and private organizations, and news articles. Results: To shorten approval lag, it is recommended to hire and train more reviewers at the Ministry of Food and Drug Safety. Increasing user fees to a realistic level can facilitate this process. To reduce reimbursement lag, flexible incremental cost-effectiveness ratio threshold, alternative cost-effectiveness evaluation, and establishment of funding source other than the national health insurance are identified as the areas to be improved. Conclusion The current policies and regulations had to be supplemented by new systems to drastically promote patient accessibility to new drugs, consequently in order to promote national public health.

Background: Patients with atopic dermatitis (AD) are vulnerable to xerosis due to impaired skin barrier function, which makes moisturizing essential. Recently, zinc-alpha-2 glycoprotein (ZAG) has appeared to modulate the skin barrier function in AD, and has been proposed as a potential therapeutic molecule in AD. Objective: This study aimed to evaluate the effects of a ZAG-containing moisturizer on restoration of the skin barrier and clinical improvement of AD. Methods: In this randomized, double-blind study, 42 patients (average age, 26.5 years) with mild-to-moderate AD were enrolled. The subjects were divided into two groups, ZAG-containing moisturizer or control, in which the intervention or control were applied twice a day for 4 weeks. The primary outcome was a change in the eczema area and severity index (EASI) after 4 weeks, and the secondary outcome included the transepidermal water loss (TEWL), corneometer, visual assessment score (VAS) for pruritus and sleep disturbance, and investigator’s global assessment (IGA). Results ZAG-containing moisturizer was well-tolerated, with a significant decrease in the EASI score compared to the control group after 4 weeks of application (p＜0.05). As objective assessments of skin barrier function, TEWL also showed a significant, rapid decrease in the ZAG group compared to the control group after 2 weeks of application (p＜0.05). A significant improvement in AD symptoms was observed at 4 weeks, such as the VAS score for pruritus and sleep disturbance, and IGA. Conclusion: The moisturizer containing ZAG (By the doctor Ato repair cream , Whitecospharm, Korea) effectively restored the function of the skin barrier, which led to a relief in the signs and symptoms of AD.

Background: s: The severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) has spread worldwide. Cardiac injury after SARS-CoV-2 infection is a major concern. The present study investigated impact of the biomarkers indicating cardiac injury in coronavirus disease 2019 (COVID-19) on patients' outcomes. Methods: This study enrolled patients who were confirmed to have COVID-19 and admitted at a tertiary university referral hospital between February 19, 2020 and March 15, 2020. Cardiac injury was defined as an abnormality in one of the following result markers: 1) myocardial damage marker (creatine kinase-MB or troponin-I), 2) heart failure marker (N-terminal-pro B-type natriuretic peptide), and 3) electrical abnormality marker (electrocardiography). The relationship between each cardiac injury marker and mortality was evaluated. Survival analysis of mortality according to the scoring by numbers of cardiac injury markers was also performed. Results: A total of 38 patients with COVID-19 were enrolled. Twenty-two patients (57.9%) had at least one of cardiac injury markers. The patients with cardiac injuries were older (69.6 ± 14.9 vs. 58.6 ± 13.9 years old, P = 0.026), and were more male (59.1% vs. 18.8%, P = 0.013).They showed lower initial oxygen saturation (92.8 vs. 97.1%, P = 0.002) and a trend toward higher mortality (27.3 vs. 6.3%, P = 0.099). The increased number of cardiac injury markers was significantly related to a higher incidence of in-hospital mortality which was also evidenced by Kaplan-Meier survival analysis (P = 0.008). Conclusion The increased number of cardiac injury markers is related to in-hospital mortality in patients with COVID-19.