Lazertinib is an oral, third-generation, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) for the treatment of non-small cell lung cancer (NSCLC). This case report presents a rare instance of small cell carcinoma transformation in pancreatic metastasis in a patient with EGFR-mutated NSCLC undergoing treatment with lazertinib. Small cell carcinoma transformation indicates a mechanism of treatment resistance, and tissue biopsy is essential to confirm this. When isolated progression of a lesion is suspected during TKI therapy in EGFR-mutated NSCLC, histological evaluation is necessary to confirm the transformation for the treatment strategy.

Purpose: To compare the macular and peripapillary vascular parameters between the primary angle closure suspect (PACS) eyes and normal control eyes using optical coherence tomography angiography (OCTA). Methods: In this retrospective study, 42 PACS subjects and 38 normal individuals are included. Vessel density (VD) and perfusion density (PD) of the macular area and peripapillary area, and fovea avascular zone parameter were analyzed using OCTA and compared between two groups after adjustment for the axial length. Results: There were no statistically significant differences in sex ratio, age, refractive errors and intraocular pressures between both groups. In the peripapillary area, inferior VD and PD in the outer zone were significantly lower in the PACS eyes, while the retinal nerve fiber layer thicknesses were similar between groups (p = 0.032, 0.026). In the macular superficial capillary plexus, inferior VD and PD in the inner zone, inferior VD and PD, nasal VD and PD in the outer zone were significantly lower in the PACS eyes, whereas ganglion cell inner plexiform layer thickness were similar between both groups (all p < 0.005). Conclusions The VDs and PDs of retinal capillaries in PACS eyes, which have no glaucomatous changes in the retinal nerve fiber layer and optic nerve disc, were significantly lower compared to normal eyes.

Objective: Acute coronary syndrome often requires urgent intervention. The 2023 European Society of Cardiology guidelines recommend invasive procedures within 24 hours for high-risk cases. Nevertheless, there have been limited studies on non-ST-segment elevation myocardial infarction (NSTEMI) in South Korea. This study compared the risk of complications based on the timing of intervention. Methods: A retrospective observational study was conducted on patients with chest pain and elevated high-sensitivity troponin T from January to December 2021 in the emergency department. Patients were categorized into early (≤24 hr) and late (>24 hr) intervention groups. Primary outcomes (death, restenosis, or stroke) at 12 months were compared. Survival and subgroup analyses were performed to examine the factors affecting the outcomes in the two groups. Results: Three hundred seventy six patients were enrolled in the study, and 115 patients were excluded. Among 261 patients, 106 and 155 patients were in the early intervention group (≤24 hr), and late intervention group (>24 hr), respectively. The primary outcome (death or restenosis) showed no significant difference (hazard ratio [HR] in the early intervention group at 12 mo; 1.03; 95% confidence interval [CI], 0.63-1.70; P=0.905). However, risk of stroke was lower in the early intervention group (HR in the early, 0.08; 95% CI, 0.00-0.66; P=0.013). Subgroup analysis showed no significant advantage for early intervention. Conclusion In NSTEMI patients, early intervention does not reduce death or restenosis but lowers stroke incidence. No specific risk factors favored early intervention.

Purpose: In this study, we investigated the effect of bisphenol-A (BPA) and its major analogs, bisphenol-F (BPF), and bisphenol-S (BPS), on spermatogonial stem cells (SSCs) populations using in vitro SSC culture and in vivo transplantation models. Materials and Methods: SSCs enriched from 6- to 8-day-old C57BL/6-eGFP+ male mice testes were treated with varying concentrations of bisphenols for 7 days to examine bisphenol-derived cytotoxicity and changes in SSC characteristics. We utilized flow cytometry, immunocytochemistry, real-time quantitative reverse transcription-PCR, and western blot analysis. The functional alteration of SSCs was further investigated by examining donor SSC-derived spermatogenesis evaluation through in vivo transplantation and subsequent testis analysis. Results: BPF exhibited a similar inhibitory effect on SSCs as BPA, demonstrating a significant decrease in SSC survival, inhibition of proliferation, and induction of apoptosis. On the other hand, while BPS was comparatively weaker than BPA and BPF, it still showed significant SSC cytotoxicity. Importantly, SSCs exposed to BPA, BPF, and BPS exhibited a significant reduction in donor SSC-derived germ cell colonies per total number of cultured cells, indicating that, like BPA, BPF, and BPS can induce a comparable reduction in functional SSCs in the recipient animals. However, the progress of spermatogenesis, as evidenced by histochemistry and the expressions of PCNA and SSC specific markers, collectively indicates that BPA, BPF, and BPS may not adversely affect the spermatogenesis. Conclusions Our findings indicate that the major BPA substitutes, BPF and BPS, have significant cytotoxic effects on SSCs, similar to BPA. These effects may lead to a reduction in the functional self-renewal stem cell population and potential impacts on male fertility.

Background: Respiratory infections play a major role in acute exacerbation of chronic obstructive pulmonary disease (AECOPD). This study assessed the prevalence of bacterial and viral pathogens and their clinical impact on patients with AECOPD. Methods: This retrospective study included 1,186 patients diagnosed with AECOPD at 28 hospitals in South Korea between 2015 and 2018. We evaluated the identification rates of pathogens, basic patient characteristics, clinical features, and the factors associated with infections by potentially drug-resistant (PDR) pathogens using various microbiological tests. Results: Bacteria, viruses, and both were detected in 262 (22.1%), 265 (22.5%), and 129 (10.9%) of patients, respectively. The most common pathogens included Pseudomonas aeruginosa (17.8%), Mycoplasma pneumoniae (11.2%), Streptococcus pneumoniae (9.0%), influenza A virus (19.0%), rhinovirus (15.8%), and respiratory syncytial virus (6.4%). Notably, a history of pulmonary tuberculosis (odds ratio [OR], 1.66; p=0.046), bronchiectasis (OR, 1.99; p=0.032), and the use of a triple inhaler regimen within the past 6 months (OR, 2.04; p=0.005) were identified as significant factors associated with infection by PDR pathogens. Moreover, patients infected with PDR pathogens exhibited extended hospital stays (15.9 days vs. 12.4 days, p=0.018) and higher intensive care unit admission rates (15.9% vs. 9.5%, p=0.030). Conclusion This study demonstrates that a variety of pathogens are involved in episodes of AECOPD. Nevertheless, additional research is required to confirm their role in the onset and progression of AECOPD.

Background: Lung ultrasound (LUS) has proven valuable in the initial assessment of coronavirus disease 2019 (COVID-19), but its role in detecting pulmonary fibrosis following intensive care remains unclear. This study aims to assess the presence of pulmonary sequelae and fibrosis-like changes using LUS in survivors of severe COVID-19 pneumonia one month after discharge. Methods: We prospectively enrolled patients with severe COVID-19 who required mechanical ventilation in the intensive care unit (ICU) and conducted LUS assessments from admission to the outpatient visit after discharge. We tracked changes in key LUS findings and applied our proprietary LUS scoring system. To evaluate LUS accuracy, we correlated measured LUS values with computed tomography scores. Results: We evaluated B-line presence, pleural thickness, and consolidation in 14 eligible patients. The LUS scores exhibited minimal changes, with values of 19.1, 19.2, and 17.5 at admission, discharge, and the outpatient visit, respectively. Notably, the number of B-lines decreased significantly, from 1.92 at admission to 0.56 at the outpatient visit (p<0.05), while pleural thickness increased significantly, from 2.05 at admission to 2.48 at the outpatient visit (p≤0.05). Conclusion This study demonstrates that LUS can track changes in lung abnormalities in severe COVID-19 patients from ICU admission through to outpatient follow-up. While pleural thickening and B-line patterns showed significant changes, no correlation was found between LUS and high-resolution computed tomography fibrosis scores. These findings suggest that LUS may serve as a supplementary tool for assessing pulmonary recovery in severe COVID-19 cases.

Background: Kelch-like ECH-associated protein 1 (KEAP1)–nuclear factor erythroid- 2-related factor 2 (NRF2) pathway is a major regulator protecting cells from oxidative and metabolic stress. Studies have revealed that this pathway is involved in mediating resistance to cytotoxic chemotherapy and immunotherapy; however, its implications in oncogene-addicted tumors are largely unknown. This study aimed to elucidate whether this pathway could be a potential therapeutic target for epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer. Methods: We measured the baseline expression of NRF2 using EGFR-mutant parental cells and acquired gefitinib resistant cells. We investigated whether NRF2 inhibition affected cell death in vitro and tumor growth in vivo using a xenograft mouse model, and compared the transcriptional changes before and after NRF2 inhibition. Results: Baseline NRF2 expression was enhanced in PC9 and PC9 with gefitinib resistance (PC9/GR) cells than in other cell lines, with a more prominent expression in PC9/ GR. The NRF2 inhibitor induced NRF2 downregulation and cell death in a dose-dependent manner. Cotreatment with an NRF2 inhibitor enhanced osimertinib-induced cell death in vitro, and potentiated tumor growth inhibition in a PC9/GR xenograft model. Finally, RNA sequencing revealed that NRF2 inhibition resulted in the altered expression of multiple genes involved in various signaling pathways. Conclusion We identified that NRF2 inhibition enhanced cell death and inhibited tumor growth in tyrosine kinase inhibitor (TKI)-resistant lung cancer with EGFR-mutation. Thus, NRF2 modulation may be a novel therapeutic strategy to overcome the resistance to EGFR-TKIs.

Lazertinib is an oral, third-generation, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) for the treatment of non-small cell lung cancer (NSCLC). This case report presents a rare instance of small cell carcinoma transformation in pancreatic metastasis in a patient with EGFR-mutated NSCLC undergoing treatment with lazertinib. Small cell carcinoma transformation indicates a mechanism of treatment resistance, and tissue biopsy is essential to confirm this. When isolated progression of a lesion is suspected during TKI therapy in EGFR-mutated NSCLC, histological evaluation is necessary to confirm the transformation for the treatment strategy.

Objective: As the demand for community mental health services continues to grow, the need for well-equipped and organized services has become apparent. This study aimed to optimize the roles and infrastructure of mental health services, by establishing, among other initiatives, standardized operating models. Methods: The study was conducted in multiple phases from May 12, 2021, to December 29, 2021. Stakeholders within South Korea and metropolitan mental health welfare centers were targeted, but addiction management support centers, including officials, patients, and their families, were integrated as well. A literature review and survey, focus group interviews, a Delphi survey, and expert consultation contributed to comprehensive revisions and improvements of the mental health service model. Results: The proposed model for community mental health welfare centers emphasizes the expansion of personnel and infrastructure, with a focus on severe mental illnesses and suicide prevention. The model for metropolitan mental health welfare centers delineates essential tasks in areas such as project planning and establishment, community research, and education about severe mental illnesses. The establishment of a 24-hour emergency intervention center was a crucial feature. In the integrated addiction support center model, the need to promote addiction management is defined as an essential task and the establishment of national governance for addiction policies is recommended. Conclusion This study proposed standard operating models for three types of mental health service centers. To meet the increasing need for community care, robust mental health service delivery systems are of primary importance.