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.

Acute Respiratory Distress Syndrome (ARDS) is a severe condition characterized by extensive lung inflammation and increased alveolar-capillary permeability, often triggered by infections or systemic inflammatory responses. Mesenchymal stem cells (MSCs)-based therapy holds promise for treating ARDS, as MSCs manifest immunomodulatory and regenerative properties that mitigate inflammation and enhance tissue repair. Primed MSCs, modified to augment specific functionalities, demonstrate superior therapeutic efficacy in targeted therapies compared to naive MSCs. This study explored the immunomodulatory potential of MSCs using mixed lymphocyte reaction (MLR) assays and co-culture experiments with M1/M2 macrophages. Additionally, RNA sequencing was employed to identify alterations in immune and inflammation-related factors in primed MSCs. The therapeutic effects of primed MSCs were assessed in an LPS-induced ARDS mouse model, and the underlying mechanisms were investigated through spatial transcriptomics analysis. The study revealed that MSCs primed with IFN-γ and IL-1β significantly enhanced the suppression of T cell activity compared to naive MSCs, concurrently inhibiting TNF-α while increasing IL-10 production in macrophages. Notably, combined treatment with these two cytokines resulted in a significant upregulation of immune and inflammation-regulating factors. Furthermore, our analyses elucidated the mechanisms behind the therapeutic effects of primed MSCs, including the inhibition of inflammatory cell infiltration in lung tissue, modulation of immune and inflammatory responses, and enhancement of elastin fiber formation. Signaling pathway analysis confirmed that efficacy could be enhanced by modulating NFκB and TNF-α signaling. In conclusion, in early-phase ARDS, primed MSCs displayed enhanced homing capabilities, improved lung function, and reduced inflammation.

Genetic kidney diseases are caused by mutations in specific genes that significantly affect kidney development and function. Although the underlying pathogenic genes of many kidney diseases have been identified, an understanding of their mechanisms and effective treatments remains limited. Gene editing, particularly using clustered regularly interspaced short palindromic repeats (CRISPR), has recently become a promising approach for studying genetic diseases and the CRISPR/CRISPR-associated protein 9 (CRISPR-Cas9) method has become a prominent research method. It has been shown that CRISPR-Cas9 can be targeted to knock out specific genomic sites, which enables researchers to correct gene mutations, prevent inheritance, and better understand the function of genes and the effectiveness of drugs. However, the application of CRISPR-Cas9 technology in the development of therapeutic agents against genetic kidney disease has been overlooked compared with other genetic diseases. In this paper, we provide an overview of the current research advancements in genetic kidney diseases using CRISPR technology, as well as the diverse preclinical research methods implemented, with particular emphasis on autosomal dominant polycystic kidney disease.

Objective: This study investigated how educational levels modify the relationship between the standard deviation of NN intervals (SDNN) of heart rate variability and the development of post-traumatic stress disorder (PTSD). Methods: Participants with physical injuries were enrolled from a trauma center and monitored over two years. Initial assessments included SDNN and educational attainment, along with socio-demographic and clinical variables. PTSD diagnoses were made at 3, 6, 12, and 24 months post-injury using the Clinician-Administered PTSD Scale for DSM-5.Logistic regression analyses were conducted. Results: Of the 538 participants, 58 (10.8%) developed PTSD during the follow-up period. A significant interaction effect was observed: lower SDNN was significantly linked to PTSD in individuals with higher education, but not in those with lower education. Conclusion The study identified education-dependent associations between SDNN and PTSD development, emphasizing the importance of tailored PTSD prevention strategies that consider both SDNN and educational levels.

Background: The treatment of Kümmell disease (KD) is controversial. Corpectomy and reconstruction or osteotomy with long-level fusion was traditionally performed for the advanced KD. However, these procedures can be disadvantageous for elderly patients.Several alternative surgical procedures including transpedicular intravertebral cage augmentation (TPICA) or vertebroplasty (VP) combined with short-segment fixation (SSF) have been suggested to minimize the surgical burden. This study aimed to compare the outcomes of percutaneous TPICA plus SSF with VP plus SSF for advanced thoracolumbar (T11–L2) KD and to introduce our novel percutaneous TPICA technique using specially designed cannulated cage trials. Methods: We devised specially designed cannulated cage trials to make the TPICA procedure safer and more reproducible, minimizing the risk of the pedicle medial wall violation. All consecutive patients who underwent percutaneous TPICA or VP combined with SSF for advanced thoracolumbar KD, from January 2021 to June 2022, with ≥ 1-year follow-up at a single institution, were included. Perioperative details, clinical outcomes (visual analog scale and Oswestry Disability Index), and radiological outcomes (anterior vertebral body compression percentage and vertebral kyphotic angle [VKA] of the fractured vertebra, and local Cobb angle [LCA]) were collected and compared between the groups. Results: A total of 42 patients were enrolled, with 21 patients in each group. There were no patients with pedicle medial wall fracture in the TPICA group. Both procedures provided significantly favorable radiological outcomes compared to those preoperatively. No significant differences were observed in the changes over time in all radiological parameters between the groups. Loss of correction during the follow-up period was significantly smaller in patients with TPICA than in those with VP in VKA (median [interquartile range], 2.15 [0.30–2.80] vs. 2.90 [0.90–6.53]; p = 0.030) and LCA (2.70 ± 2.90 vs. 5.17 ± 4.40, p = 0.037). Conclusions Both procedures are minimally invasive and useful options for advanced KD, especially for elderly patients with high comorbidity. Our novel percutaneous TPICA technique using cannulated cage trials, being safer and more reproducible, may allow spine surgeons to easily perform TPICA.

Background: and Purpose: This clinical practice guideline provides evidence-based recommendations for treatment of dementia, focusing on cholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists for Alzheimer’s disease (AD) and other types of dementia. Methods: Using the Population, Intervention, Comparison, Outcomes (PICO) framework, we developed key clinical questions and conducted systematic literature reviews. A multidisciplinary panel of experts, organized by the Korean Dementia Association, evaluated randomized controlled trials and observational studies. Recommendations were graded for evidence quality and strength using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. Results: Three main recommendations are presented: (1) For AD, cholinesterase inhibitors (donepezil, rivastigmine, galantamine) are strongly recommended for improving cognition and daily function based on moderate evidence; (2) Cholinesterase inhibitors are conditionally recommended for vascular dementia and Parkinson’s disease dementia, with a strong recommendation for Lewy body dementia; (3) For moderate to severe AD, NMDA receptor antagonist (memantine) is strongly recommended, demonstrating significant cognitive and functional improvements. Both drug classes showed favorable safety profiles with manageable side effects. Conclusions This guideline offers standardized, evidence-based pharmacologic recommendations for dementia management, with specific guidance on cholinesterase inhibitors and NMDA receptor antagonists. It aims to support clinical decision-making and improve patient outcomes in dementia care. Further updates will address emerging treatments, including amyloid-targeting therapies, to reflect advances in dementia management.

Background: and Purpose Treatments for neuromyelitis optica spectrum disorder (NMOSD) such as eculizumab, ravulizumab, satralizumab, and inebilizumab have significantly advanced relapse prevention, but they remain expensive. Rituximab is an off-label yet popular alternative that offers a cost-effective solution, but its real-world efficacy needs better quantification for guiding the application of newer approved NMOSD treatments (ANTs). This study aimed to determine real-world rituximab failure rates to anticipate the demand for ANTs and aid in resource allocation. Methods: We conducted a nationwide retrospective study involving 605 aquaporin-4-antibody-positive NMOSD patients from 22 centers in South Korea that assessed the efficacy and safety of rituximab over a median follow-up of 47 months. Results: The 605 patients treated with rituximab included 525 (87%) who received continuous therapy throughout the follow-up period (median=47 months, interquartile range=15–87 months). During this period, 117 patients (19%) experienced at least 1 relapse. Notably, 68 of these patients (11% of the total cohort) experienced multiple relapses or at least 1 severe relapse.Additionally, 2% of the patients discontinued rituximab due to adverse events, which included severe infusion reactions, neutropenia, and infections. Conclusions This study has confirmed the efficacy of rituximab in treating NMOSD, as evidenced by an 87% continuation rate among patients over a 4-year follow-up period. Nevertheless, the occurrence of at least one relapse in 19% of the cohort, including 11% who experienced multiple or severe relapses, and a 2% discontinuation rate due to adverse events highlight the urgent need for alternative therapeutic options.

Purpose: Since 1995, the Korean Gastric Cancer Association (KGCA) has been periodically conducting nationwide surveys on patients with surgically treated gastric cancer. This study details the results of the survey conducted in 2023. Materials and Methods: The survey was conducted from March to December 2024 using a standardized case report form. Data were collected on 86 items, including patient demographics, tumor characteristics, surgical procedures, and surgical outcomes. The results of the 2023 survey were compared with those of previous surveys. Results: Data from 12,751 cases were collected from 66 institutions. The mean patient age was 64.6 years, and the proportion of patients aged ≥71 years increased from 9.1% in 1995 to 31.7% in 2023. The proportion of upper-third tumors slightly decreased to 16.8% compared to 20.9% in 2019. Early gastric cancer accounted for 63.1% of cases in 2023.Regarding operative procedures, a totally laparoscopic approach was most frequently applied (63.2%) in 2023, while robotic gastrectomy steadily increased to 9.5% from 2.1% in 2014.The most common anastomotic method was the Billroth II procedure (48.8%) after distal gastrectomy and double-tract reconstruction (51.9%) after proximal gastrectomy in 2023.However, the proportion of esophago-gastrostomy with anti-reflux procedures increased to 30.9%. The rates of post-operative mortality and overall complications were 1.0% and 15.3%, respectively. Conclusions The results of the 2023 nationwide survey demonstrate the current status of gastric cancer treatment in Korea. This information will provide a basis for future gastric cancer research.

Gastric cancer is one of the most common cancers in both Korea and worldwide. Since 2004, the Korean Practice Guidelines for Gastric Cancer have been regularly updated, with the 4th edition published in 2022. The 4th edition was the result of a collaborative work by an interdisciplinary team, including experts in gastric surgery, gastroenterology, endoscopy, medical oncology, abdominal radiology, pathology, nuclear medicine, radiation oncology, and guideline development methodology. The current guideline is the 5th version, an updated version of the 4th edition. In this guideline, 6 key questions (KQs) were updated or proposed after a collaborative review by the working group, and 7 statements were developed, or revised, or discussed based on a systematic review using the MEDLINE, Embase, Cochrane Library, and KoreaMed database. Over the past 2 years, there have been significant changes in systemic treatment, leading to major updates and revisions focused on this area.Additionally, minor modifications have been made in other sections, incorporating recent research findings. The level of evidence and grading of recommendations were categorized according to the Grading of Recommendations, Assessment, Development and Evaluation system. Key factors for recommendation included the level of evidence, benefit, harm, and clinical applicability. The working group reviewed and discussed the recommendations to reach a consensus. The structure of this guideline remains similar to the 2022 version.Earlier sections cover general considerations, such as screening, diagnosis, and staging of endoscopy, pathology, radiology, and nuclear medicine. In the latter sections, statements are provided for each KQ based on clinical evidence, with flowcharts supporting these statements through meta-analysis and references. This multidisciplinary, evidence-based gastric cancer guideline aims to support clinicians in providing optimal care for gastric cancer patients.