Purpose: This subgroup analysis of the Korean subset of patients in the phase 3 LASER301 trial evaluated the efficacy and safety of lazertinib versus gefitinib as first-line therapy for epidermal growth factor receptor mutated (EGFRm) non–small cell lung cancer (NSCLC). Materials and Methods: Patients with locally advanced or metastatic EGFRm NSCLC were randomized 1:1 to lazertinib (240 mg/day) or gefitinib (250 mg/day). The primary endpoint was investigator-assessed progression-free survival (PFS). Results: In total, 172 Korean patients were enrolled (lazertinib, n=87; gefitinib, n=85). Baseline characteristics were balanced between the treatment groups. One-third of patients had brain metastases (BM) at baseline. Median PFS was 20.8 months (95% confidence interval [CI], 16.7 to 26.1) for lazertinib and 9.6 months (95% CI, 8.2 to 12.3) for gefitinib (hazard ratio [HR], 0.41; 95% CI, 0.28 to 0.60). This was supported by PFS analysis based on blinded independent central review. Significant PFS benefit with lazertinib was consistently observed across predefined subgroups, including patients with BM (HR, 0.28; 95% CI, 0.15 to 0.53) and those with L858R mutations (HR, 0.36; 95% CI, 0.20 to 0.63). Lazertinib safety data were consistent with its previously reported safety profile. Common adverse events (AEs) in both groups included rash, pruritus, and diarrhoea. Numerically fewer severe AEs and severe treatment–related AEs occurred with lazertinib than gefitinib. Conclusion Consistent with results for the overall LASER301 population, this analysis showed significant PFS benefit with lazertinib versus gefitinib with comparable safety in Korean patients with untreated EGFRm NSCLC, supporting lazertinib as a new potential treatment option for this patient population.

Purpose: Depression and frailty are common health problems that occur separately or simultaneously in later life. The two syndromes are correlated, but they need to be distinguished to promote successful aging. Previous studies have examined the reciprocal relationship between depression and frailty, but there are limitations in the methods or statistical analysis. This study aims to confirm the potential prospective bidirectional and causal relationship between depression and frailty. Methods: We used data from 887 older adults aged 70 to 84 from the Korean Frailty and Aging Cohort Study (KFACS) in 2016, 2018, and 2020 (3 waves). We separated the within-individual process from the stable between-individual differences using the random intercepts cross-lagged panel model. Results: Significant bidirectional causal effects were observed in 2 paths. Older adults with higher depression than their within-person average at T1 had a higher risk of frailty at T2 (β=.22, p=.008). Subsequently, older adults with higher-than-average frailty scores at T2 showed higher depression at T3 (β=.14, p=.010). Autoregressive effects were only significant from T2 to T3 for both constructs (Depression: β=.16, p=.044; Frailty: β=.13, p=.028). At the between-person level, the correlation was significant between the random intercepts between depression and frailty (β=.47, p<.001). Conclusions We find that depressed older adults have an increased risk of frailty, which contributes to the onset of depression and the maintenance of frailty. Therefore, interventions for each condition may prevent the entry and worsening of the other condition, as well as prevent comorbidity.

Xanthogranulomatous osteomyelitis is a rare, chronic inflammatory disease characterized by infiltrating lipidized histiocytes, lymphocytes, and plasma cells. Xanthogranulomatous osteomyelitis commonly presents as a mass-like lesion on imaging and may be mistaken for a tumor. Here, we describe an unusual manifestation of xanthogranulomatous osteomyelitis with imaging findings resembling those of Brodie’s abscess, posing a diagnostic challenge in a child. Additionally, we suggest a potential correlation between xanthogranulomatous osteomyelitis and a history of prior trauma.

Immune checkpoint inhibitor (ICI), including programmed cell death protein 1 and cytotoxic T-lymphocyte-associated protein 4 inhibitors, has emerged as a pillar in the management of advanced malignancies. A drug-induced sarcoidosis-like reaction (DISR) is a rare cutaneous adverse event of ICI. A 47-year-old male presented with one-month history of a solitary erythematous nodule on his forehead. He had been diagnosed with metastatic adenocarcinoma of the lung and was treated with nivolumab and ipilimumab for three months. Histological findings revealed multinucleated giant cells forming non-caseating granulomas with moderate peripheral lymphocyte infiltration in the dermis. Also, new hilar lymphadenopathy of the lung was identified in a systemic evaluation. Given the temporal relationship with ICI treatment, the final diagnosis was ICI-induced sarcoidosis-like reaction. To our knowledge, this is the first report of a case of DISR that developed following ICI treatment in the dermatologic literature in Korea.

Objectives: . Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular disorder characterized by recurrent epistaxis, telangiectasia, and visceral arteriovenous malformations (AVMs). Activin A receptor-like type 1 (ACVRL1/ALK1) and endoglin (ENG) are the principal genes whose mutations cause HHT. No multicenter study has yet investigated correlations between genetic variations and clinical outcomes in Korean HHT patients. Methods: . Seventy-two members from 40 families suspected to have HHT based on symptoms were genetically screened for pathogenic variants of ACVRL1 and ENG. Patients with genetically diagnosed HHT were also evaluated. Results: . In the HHT genetic screening, 42 patients from 24 of the 40 families had genetic variants that met the pathogenic criteria (pathogenic very strong, pathogenic strong, pathogenic moderate, or pathogenic supporting) based on the American College of Medical Genetics and Genomics Standards and Guidelines for either ENG or ACVRL1: 26 from 12 families (50%) for ENG, and 16 from 12 families (50%) for ACVRL1. Diagnostic screening of 42 genetically positive HHT patients based on the Curaçao criteria revealed that 24 patients (57%) were classified as having definite HHT, 17 (41%) as having probable HHT, and 1 (2%) as unlikely to have HHT. Epistaxis was the most common clinical presentation (38/42, 90%), followed by visceral AVMs (24/42, 57%) and telangiectasia (21/42, 50%). Five patients (12%) did not have a family history of HHT clinical symptoms. Conclusion . Only approximately half of patients with ACVRL1 or ENG genetic variants could be clinically diagnosed as having definite HHT, suggesting that genetic screening is important to confirm the diagnosis.

Background: Papillary breast lesions (PBLs) comprise diverse entities from benign and atypical lesions to malignant tumors. Although PBLs are characterized by a papillary growth pattern, it is challenging to achieve high diagnostic accuracy and reproducibility. Thus, we investigated the diagnostic reproducibility of PBLs in core needle biopsy (CNB) specimens with World Health Organization (WHO) classification. Methods: Diagnostic reproducibility was assessed using interobserver variability (kappa value, κ) and agreement rate in the pathologic diagnosis of 60 PBL cases on CNB among 20 breast pathologists affiliated with 20 medical institutions in Korea. This analysis was performed using hematoxylin and eosin (H&E) staining and immunohistochemical (IHC) staining for cytokeratin 5 (CK5) and p63. The pathologic diagnosis of PBLs was based on WHO classification, which was used to establish simple classifications (4-tier, 3-tier, and 2-tier). Results: On WHO classification, H&E staining exhibited ‘fair agreement’ (κ = 0.21) with a 47.0% agreement rate. Simple classifications presented improvement in interobserver variability and agreement rate. IHC staining increased the kappa value and agreement rate in all the classifications. Despite IHC staining, the encapsulated/solid papillary carcinoma (EPC/SPC) subgroup (κ = 0.16) exhibited lower agreement compared to the non-EPC/SPC subgroup (κ = 0.35) with WHO classification, which was similar to the results of any other classification systems. Conclusions Although the use of IHC staining for CK5 and p63 increased the diagnostic agreement of PBLs in CNB specimens, WHO classification exhibited a higher discordance rate compared to any other classifications. Therefore, this result warrants further intensive consensus studies to improve the diagnostic reproducibility of PBLs with WHO classification.

Purpose: The aim of this study was to investigate celiac plexus neurolysis (CPN) for the treatment of cancerous upper abdominal pain in a tertiary university hospital in Korea. Methods: At the tertiary university hospital in Korea, electronic medical records of cancer patients who underwent CPN and died in the hospital from November 2009 to June 2018 were retrospectively analyzed. Results: The total number of subjects was 51. The 17 patients were from the Department of Gastroenterology (33.0%), followed by 11 patients from the Department of Hemato-oncology (21.6%), 11 patients from the Department of Anesthesia and Pain Medicine (21.6%), 9 patients from the Department of General Surgery (17.6%). The diagnosis was pancreatic cancer in 15 patients (29.4%), stomach cancer in 8 patients (15.7%), hepatobiliary cancer in 20 patients (39.2%), colon cancer in 1 patient (2.0%), esophageal cancer in 2 patient (3.9%) and intra-abdominal metastasis in 5 patients (9.8%). The mean survival time after the surgery was 66.4±55.0 days. The pain intensity before and 1 week after the procedure significantly decreased, but the amounts of opioids consumed before and 1 week after the procedure were not statistically significant. Side effects occurred after the procedure including temporary localized pain in 24 patients (47.0%), hypotension in 12 (23.5%), and diarrhea in 6 (11.8%). Conclusion CPN is an effective and safe procedure for reducing upper abdominal pain caused by cancer, and it is necessary to perform CPN within the appropriate time by establishing a system of interdepartmental cooperation.

BACKGROUND/OBJECTIVES: Inflammatory Bowel Disease (IBD) has rapidly escalated in Asia (including Korea) due to increasing westernized diet patterns subsequent to industrialization. Factors associated with endoplasmic reticulum (ER) stress are demonstrated to be one of the major causes of IBD. This study was conducted to investigate the effect of Lycium barbarum (L. barbarum) on ER stress. MATERIALS/METHODS: Mouse embryonic fibroblast (MEF) cell line and polarized Caco-2 human intestinal epithelial cells were treated with crude extract of the L. chinense fruit (LF). Paracellular permeability was measured to examine the effect of tight junction (TJ) integrity. The regulatory pathways of ER stress were evaluated in MEF knockout (KO) cell lines by qPCR for interleukin (IL) 6, IL8 and XBP1 spliced form (XBP1s). Immunoglobulin binding protein (BiP), XBP1s and CCAAT/enhancer-binding homologous protein (CHOP) expressions were measured by RT-PCR. Scanning Ion Conductance Microscopy (SICM) at high resolution was applied to observe morphological changes after treatments. RESULTS: Exposure to LF extract strengthened the TJ, both in the presence and absence of inflammation. In polarized Caco-2 pretreated with LF, induction in the expression of proinflammatory marker IL8 was not significant, whereas ER stress marker XBP1s expression was significantly increased. In wild type (wt) MEF cells, IL6, CHOP and XBP1 spliced form were dose-dependently induced when exposed to 12.5–50 µg/mL extract. However, absence of XBP1 or IRE1α in MEF cells abolished this effect. CONCLUSION: Results of this study show that LF treatment enhances the barrier function and reduces inflammation and ER stress in an IRE1α-XBP1-dependent manner. These results suggest the preventive effect of LF on healthy intestine, and the possibility of reducing the degree of inflammatory symptoms in IBD patients.
Animals ; Asia ; Carrier Proteins ; Cell Line ; Diet ; Endoplasmic Reticulum ; Epithelial Cells ; Fibroblasts ; Fruit ; Humans ; Immunoglobulins ; Inflammation ; Inflammatory Bowel Diseases ; Interleukin-6 ; Interleukin-8 ; Interleukins ; Intestines ; Lycium ; Mice ; Microscopy ; Permeability ; Tight Junctions

PURPOSE: The purpose of this study is to examine and share experiences of male nurses who have been rejected during their nursing practice by their patients. METHODS: The participants were 12 male nurses who have worked in several hospitals. Data were collected through personalized in-depth interviews. Collected data were analyzed with the content analysis method. RESULTS: The results can be categorized into three main themes. 1. Rejection based on gender stereotypes of nurses' roles. 2. Nurses' reactions when nursing was rejected 3. Reestablishing the role as a nurse. The results of this study showed that male nurses were struggling to maintain their own positions as professional nurses. They were refused by their patients and they experienced a lack of skill and knowledge in nursing practice. They were harmed physically and psychologically from being turned down, and sometimes they had serious conflicts with female nurses. Meanwhile, the male nurses tried to be faithful to their role as professional nurses. CONCLUSION: The results of this study show the following findings. 1. The male nurses' experiences where mostly ones of understanding and cooperation with patients' caregivers. 2. The need for public relations advertising and systematic support from the media. 3. The need for improving gender equality for nurses. 4. Strengthening male nursing students' endeavors for sound nursing professionalism.
Caregivers ; Female ; Humans ; Male ; Methods ; Nurses, Male ; Nursing ; Professionalism ; Public Relations ; Qualitative Research

An abnormal reorganization of the dentate gyrus and neurotoxic events are important phenotypes in the hippocampus of patients with temporal lobe epilepsy (TLE). The effects of morin, a bioflavonoid constituent of many herbs and fruits, on epileptic seizures have not yet been elucidated, though its beneficial effects, such as its anti-inflammatory and neuroprotective properties, are well-described in various neurodegenerative diseases. In the present study, we investigated whether treatment with morin hydrate (MH) can reduce the susceptibility to seizures, granule cell dispersion (GCD), mammalian target of rapamycin complex 1 (mTORC1) activity, and the increases in the levels of apoptotic molecules and inflammatory cytokines in the kainic acid (KA)-induced seizure mouse model. Our results showed that oral administration of MH could reduce susceptibility to seizures and lead to the inhibition of GCD and mTORC1 activity in the KA-treated hippocampus. Moreover, treatment with MH significantly reduced the increased levels of apoptotic signaling molecules and pro-inflammatory mediators in the KA-treated hippocampus compared with control mice, suggesting a neuroprotective role. Therefore, these results suggest that morin has a therapeutic potential against epilepsy through its abilities to inhibit GCD and neurotoxic events in the in vivo hippocampus.
Administration, Oral ; Animals ; Cytokines ; Dentate Gyrus ; Epilepsy ; Epilepsy, Temporal Lobe ; Fruit ; Hippocampus ; Humans ; Kainic Acid ; Mice ; Neurodegenerative Diseases ; Neuroprotection ; Phenotype ; Seizures* ; Sirolimus