1.KEAP1-NRF2 Pathway as a Novel Therapeutic Target for EGFR-Mutant Non-small Cell Lung Cancer
Jae-Sun CHOI ; Hye-Min KANG ; Kiyong NA ; Jiwon KIM ; Tae-Woo KIM ; Junyang JUNG ; Heejin LIM ; Hyewon SEO ; Seung Hyeun LEE
Tuberculosis and Respiratory Diseases 2025;88(1):138-149
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.
2.Conventional versus Instillation Negative-Pressure Wound Therapy for Severe Soft Tissue Injury in Open Pelvic Fractures: A Retrospective Review
Donghwan CHOI ; Won Tae CHO ; Hyung Keun SONG ; Junsik KWON ; Byung Hee KANG ; Hohyung JUNG ; Min Ji KIM ; Kyoungwon JUNG
Yonsei Medical Journal 2025;66(2):94-102
Purpose:
We investigated the clinical features, current negative-pressure wound therapy (NPWT) management strategies, and outcomes of pelvic-perineal soft tissue infection after open pelvic fractures.
Materials and Methods:
We analyzed the data of patients admitted to our trauma center with pelvic-perineal soft tissue after open pelvic fractures over a 7-year period. We investigated the injury severity score (ISS), medical costs, number of NPWTs, time required to reach definite wound coverage, complications, fracture classifications, transfusion requirements, interventions, length of stay (LOS) in hospital and intensive care unit (ICU), and prognosis.
Results:
Twenty patients with open pelvic fractures were treated with NPWT, and one patient who underwent NPWT died of pelvic sepsis during ICU treatment. The median LOS in hospital and medical costs were 98 [56–164] days and 106400 [65600–171100] USD, respectively. Patients treated with instillation NPWT (iNPWT, n=10) had a shorter NPWT duration (24 [13–39] vs. 46 [42–91] days, p=0.023), time to definite wound coverage (30 [21–43] vs. 49 [42–93] days, p=0.026), and hospital LOS (56 [43–72] vs. 158 [101–192] days, p=0.001), as well as lower medical costs (67800 [42500–102500] vs. 144200 [110400–236000] USD, p=0.009) compared to those treated with conventional NPWT.
Conclusion
NPWT is a feasible method for treating pelvic soft tissue infections in patients with open pelvic fractures. iNPWT can reduce the duration of NPWT, hospital LOS, and medical costs.
3.Non-Inferiority Analysis of Electrocardiography Analysis Application vs. Point-of-Care Ultrasound for Screening Left Ventricular Dysfunction
Jin Hee KIM ; Jae Yun JUNG ; Joonghee KIM ; Youngjin CHO ; Eunkyoung LEE ; Dahyeon SON
Yonsei Medical Journal 2025;66(3):172-178
Purpose:
Point-of-care ultrasound (POCUS) is widely used for heart function evaluation in emergency departments (EDs), but requires specific equipment and skilled operators. This study evaluates the diagnostic accuracy of a mobile application for estimating left ventricular (LV) systolic dysfunction [left ventricular ejection fraction (LVEF) <40%] using electrocardiography (ECG) and tests its non-inferiority to POCUS.
Materials and Methods:
Patients (aged ≥20 years) were included if they had both a POCUS-based EF evaluation and an ECG within 24 hours of their ED visit between January and May 2022, along with formal echocardiography within 2 weeks before or after the visit. A mobile app (ECG Buddy, EB) estimated LVEF (EF from EB) and the risk of LV dysfunction (LV-Dysfunction score) from ECG waveforms, which were compared to NT-proBNP levels and POCUS-evaluated LVEF (EF from POCUS). A non-inferiority margin was set at an area under the curve (AUC) difference of 0.05.
Results:
Of the 181 patients included, 37 (20.4%) exhibited LV dysfunction. The AUCs for screening LV dysfunction using POCUS and NT-proBNP were 0.885 and 0.822, respectively. EF from EB and LV-Dysfunction score outperformed NT-proBNP, with AUCs of 0.893 and 0.884, respectively (p=0.017 and p=0.030, respectively). EF from EB was non-inferior to EF from POCUS, while LV-Dysfunction score narrowly missed the mark. A subgroup analysis of sinus-origin rhythm ECGs supported the non-inferiority of both EF from EB and LV-Dysfunction score to EF from POCUS.
Conclusion
A smartphone application that analyzes ECG image can screen for LV dysfunction with a level of accuracy comparable to that of POCUS.
4.Radiological characteristics of shoulder diseases in older adults, including adhesive capsulitis, rotator cuff tear, and osteoarthritis of the glenohumeral joint: a narrative review
The Ewha Medical Journal 2025;48(1):e10-
Shoulder diseases, including adhesive capsulitis, rotator cuff tear, and osteoarthritis of the glenohumeral joint, can significantly impair daily activities in older adult patients. This review aims to examine the radiologic findings associated with these shoulder conditions in older patients, providing insights for accurate diagnosis and effective treatment. Adhesive capsulitis, commonly known as frozen shoulder, leads to pain and restricted movement, thereby causing shoulder dysfunction. Recent advances in diagnostic technology have greatly enhanced the sensitivity and accuracy of diagnosing this condition through radiologic evaluations, including MRI, magnetic resonance arthrography (MRA), and high-resolution ultrasound. Rotator cuff disease is another frequent issue in older adults, with full-thickness tears occurring in 50%–80% of cases. Both MRI and MRA are highly sensitive and specific in identifying rotator cuff tears. Additionally, ultrasonography is recognized for its high sensitivity and specificity in detecting tears of the supraspinatus tendon. Although osteoarthritis of the glenohumeral joint is less commonly prevalent, its advanced stages can severely affect the function of the upper extremity. Plain radiography is typically the first imaging technique used to assess this type of osteoarthritis. As the condition worsens, CT is utilized to measure glenoid bone loss, glenoid version, and inclination, which are crucial for accurate surgical planning. Each imaging modality provides distinct benefits: plain radiographs for initial structural assessment, ultrasonography for real-time evaluation of soft tissues, MRI/MRA for detailed visualization of capsular and tendinous lesions, and CT for precise bony analysis.
5.Prevalence and factors influencing postpartum depression and its culture-specific cutoffs for women in Asia: a scoping review
Bora MOON ; Hyun Kyoung KIM ; Ju-Hee NHO ; Hyunkyung CHOI ; ChaeWeon CHUNG ; Sook Jung KANG ; Ju Hee KIM ; Ju-Young LEE ; Sihyun PARK ; Gisoo SHIN ; Ju-Eun SONG ; Min Hee LEE ; Sue KIM
The Ewha Medical Journal 2025;48(1):e15-
The prevalence of postpartum depression (PPD) in Asia is reported to range from 13.53% to 22.31%. However, there remains a gap in the identification of PPD, particularly regarding cultural cutoff points. Therefore, the purpose of this scoping review was to determine the prevalence and associated factors of PPD in Eastern, South-eastern, Western, and Southern Asian countries and analyze the cutoff points of the Edinburgh Postnatal Depression Scale (EPDS) used across these countries. Following Arksey and O'Malley’s five-step scoping review framework, the population was defined as mothers, the concept as the EPDS, and the context as the Asian region. A literature search was conducted using PubMed, Embase, CINAHL, PsycINFO, and Web of Science. The data analysis focused on demographic characteristics, EPDS cutoffs and features, PPD prevalence, and its associated factors. Nineteen studies were selected. Most countries used translated versions of the EPDS with demonstrated reliability and validity. The cutoff scores varied, with most using scores of 10 or higher. The prevalence of PPD ranged from 5.1% to 78.7%. Key associated factors for PPD included cultural factors such as relationships with in-laws and preferences for the newborn’s sex. To improve the accuracy of PPD screening in Asia, the EPDS should be used consistently, and appropriate cutoff criteria must be established. In addition, prevention strategies and programs that reflect the cultural characteristics and social context of Asia need to be developed for the early detection and prevention of PPD.
6.Comparison of the trueness between impression techniques using scan healing abutment and conventional impression technique: an in vitro study
Kwonwoo JUNG ; Seoung-Jin HONG ; Janghyun PAEK ; Kwantae NOH ; Ahran PAE ; Hyeong-Seob KIM ; Kung-Rock KWON
The Journal of Korean Academy of Prosthodontics 2025;63(1):1-9
Purpose:
. This study evaluated the accuracy of implant impression techniques using scan healing abutments compared to conventional techniques.
Materials and methods:
. A mandibular model with implants at #34, 36, and 46 was used. Experiments were conducted for single implant and 3-unit bridge scenarios. Groups were as follows: Group IOS - Scan healing abutments were scanned with an intraoral scanner. Group Imp - Scan healing abutments were used, and impressions were taken with silicone material, followed by model scanning. Group Sb - Scan bodies were scanned with an intraoral scanner. Group Trans - Impressions were taken with transfer copings, and models were scanned. Each group was scanned 10 times, and deviations in central distance and angulation of analogs were measured. Statistical analyses were performed using ANOVA and post-hoc tests at a 95% confidence level.
Results:
. For single implants, there were no significant differences in distance deviation (P > .05). Angular deviation values were: IOS (0.24 ± 0.10°), Imp (0.19 ± 0.06°), Sb (0.38 ± 0.05°), and Trans (0.29 ± 0.06°), with Sb showing significantly larger values than IOS and Imp (P < .05). For bridges, distance deviation did not significantly differ (P > .05). Angular deviations were: IOS (0.21 ± 0.08°), Imp (0.21 ± 0.09°), Sb (0.25 ± 0.10°), and Trans (0.46 ± 0.19°), with Trans showing significantly larger values than the others (P < .05).
Conclusion
. Scan healing abutment techniques showed similar accuracy to traditional methods. They could be a viable alternative for single implant crowns or short-span fixed dental prostheses.
7.Experts’ Perceptions Regarding Testing for Helicobacter pylori Infection During Upper Gastrointestinal Endoscopy and Subsequent Eradication Therapy
Ilsoo KIM ; Sang Pyo LEE ; Jeong Wook KIM ; Heung Up KIM ; Tae Ho KIM ; Seung Young KIM ; Yu Jin KIM ; Hee Seok MOON ; Jung In LEE ; Woon Geon SHIN ;
The Korean Journal of Helicobacter and Upper Gastrointestinal Research 2025;25(1):81-86
Helicobacter pylori causes gastric cancer and peptic ulcers, and eradication therapy can reduce the incidence of cancer in high-risk groups. In Korea, discrepancies between the reimbursement criteria and clinical guidelines create clinical challenges. This study investigated the perceptions and practices of experts regarding H. pylori testing during upper gastrointestinal endoscopy and any subsequent eradication therapy. An anonymous 8-question survey was conducted among 51 experts attending the 2024 Korean College of Helicobacter and Upper Gastrointestinal Research Summer Workshop. Only 2% of the experts tested all patients. Testing was performed in 54% of patients with a family history of gastric cancer, 32% of those with atrophic gastritis, 42% of those with dyspeptic symptoms, and 62% of those with iron-deficiency anemia. Among patients with suspected infections (based on endoscopic findings) and eligible for selective reimbursement, 82% underwent H. pylori testing. Age did not influence testing decisions for 60% of the experts, and 57% considered factors other than age when deciding on eradication therapy. The practices of the experts varied depending on the patient’s clinical condition and economic burden. Aligning clinical guidelines with the reimbursement criteria is necessary to reduce confusion and ensure appropriate patient care.
8.Reduced-intensity chemotherapy with tyrosine kinase inhibitor followed by allogeneic transplantation is effective in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia
Jung Min LEE ; Do Young KIM ; Hee Jeong CHO ; Joon Ho MOON ; Sang Kyun SOHN ; Ho Jin SHIN ; Young Rok DO ; Mi Hwa HEO ; Min Kyoung KIM ; Young Seob PARK ; Dong Won BAEK
The Korean Journal of Internal Medicine 2025;40(1):124-134
Background/Aims:
To determine the effectiveness of tyrosine kinase inhibitor (TKI) plus reduced-intensity therapy in adult patients with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL), this retrospective study compared treatment outcomes and induction mortality according to backbone regimen intensity.
Methods:
The data of 132 patients diagnosed with Ph-positive ALL were retrospectively collected from five centers. Patients received imatinib plus intensive chemotherapy (modified VPD, KALLA1407, or hyper-CVAD) or reduced-intensity chemotherapy (EWALL) for curative purposes. This study analyzed 117 patients, of which 35,22,46, and 14 received modified VPD, KALLA1407, hyper-CVAD, and EWALL, respectively. All patients used imatinib as a TKI.
Results:
The median age of the patients who received reduced-intensity chemotherapy was 64.4 years, while that of the patients with intensive regimens was 47.5 years. There was no induction death in the reduced-intensity group, while nine patients died in the intensive therapy group. Major molecular response achievement tended to be higher in the intensive chemotherapy group than in the reduced-intensity group. More patients in the intensive chemotherapy group received allogeneic stem cell transplantation (allo-SCT). There was no statistically significant difference in long-term survival between the two groups in terms of relapse-free survival and overall survival rates.
Conclusions
When imatinib plus reduced-intensity therapy was used as a frontline treatment, there was no inferiority in obtaining complete remission compared to imatinib plus intensive chemotherapy or significant difference in long-term survival. Since imatinib plus reduced-intensity therapy has limitations in obtaining a deep molecular response, proceeding to allo-SCT should be considered.
9.The characteristics of Korean elderly multiple myeloma patients aged 80 years or over
Sang Hwan LEE ; Hee-Jeong CHO ; Joon Ho MOON ; Ji Yoon JUNG ; Min Kyoung KIM ; Mi Hwa HEO ; Young Rok DO ; Yunhwi HWANG ; Sung Hwa BAE
The Korean Journal of Internal Medicine 2025;40(1):115-123
Background/Aims:
Multiple myeloma (MM) predominantly affects elderly individuals, but studies on older patients with MM are limited. The clinical characteristics and survival outcomes of patients with MM aged 80 years or over were retrospectively analyzed.
Methods:
This retrospective multicenter study was conducted to investigate the clinical characteristics, treatment patterns, and survival outcomes of patients aged 80 years or over who were newly diagnosed with MM at five academic hospitals in Daegu, Korea, between 2010 and 2019.
Results:
A total of 127 patients with a median age of 83 years (range, 80–93 yr) were enrolled: 52 (40.9%) with Eastern Cooperative Oncology Group Performance Status (ECOG PS) > 2, 84 (66.1%) with International Staging System (ISS) stage III disease, and 93 (73.2%) with a Charlson comorbidity index (CCI) > 4. Chemotherapy was administered to 86 patients (67.7%). The median overall survival was 9.3 months. Overall survival was significantly associated with ECOG PS > 2 (HR 2.26, 95% CI 1.43–3.59), ISS stage III (HR 1.99, 95% CI 1.18–3.34), and chemotherapy (HR 0.34, 95% CI 0.21–0.55). There was no statistically significant difference in event-free survival according to the type of anti-myeloma chemotherapy administered. The early mortality (EM) rate was 28.3%.
Conclusions
Even in patients with MM aged 80 years or over, chemotherapy can result in better survival outcomes than supportive care. Patients aged ≥ 80 years should not be excluded from chemotherapy based on age alone. However, reducing EM in elderly patients with newly diagnosed MM remains challenging.
10.Persistent influence of past obesity on current adiponectin levels and mortality in patients with type 2 diabetes
Min-Ji KIM ; Sung-Woo KIM ; Bitna HA ; Hyang Sook KIM ; So-Hee KWON ; Jonghwa JIN ; Yeon-Kyung CHOI ; Keun-Gyu PARK ; Jung Guk KIM ; In-Kyu LEE ; Jae-Han JEON
The Korean Journal of Internal Medicine 2025;40(2):299-309
Background/Aims:
Adiponectin, a hormone primarily produced by adipocytes, typically shows an inverse relationship with body mass index (BMI). However, some studies have reported a positive correlation between the two. Thus, this study aimed to examine the relationship between adiponectin level and BMI in diabetic patients, focusing on the impact of past obesity on current adiponectin levels.
Methods:
We conducted an observational study analyzing data from 323 diabetic patients at Kyungpook National University Hospital. Based on past and current BMIs, participants were categorized into never-obese (nn, n = 106), previously obese (on, n = 43), and persistently obese (oo, n = 73) groups based on a BMI threshold of 25 kg/m2. Adiponectin level and BMI were key variables. Kaplan–Meier analysis assessed their impact on all-cause mortality up to August 2023, with survival differences based on adiponectin quartiles and follow-up starting from patient enrollment (2010–2015).
Results:
The analysis revealed a significant inverse correlation between adiponectin level and past maximum BMI. The on group exhibited approximately 10% lower adiponectin levels compared to the nn group. This association remained significant after adjusting for current BMI, age, and sex, highlighting the lasting influence of previous obesity on adiponectin levels. Furthermore, survival analysis indicated that patients in the lowest adiponectin quartile had reduced survival, with a statistically significant trend (p = 0.062).
Conclusions
Findings of this study suggest that lower adiponectin levels, potentially reflecting past obesity, are associated with decreased survival in diabetic patients, underscoring a critical role of adiponectin in long-term health outcomes.

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