Drug resistance in cancer cells remains a major obstacle limiting the clinical efficacy of current anticancer therapies. The induction of ferroptosis, an iron-dependent, regulated form of cell death, may offer an alternative therapeutic strategy to overcome such resistance. The generation of reactive oxygen species (ROS) has been implicated in this process, and depending on the cellular context, ROS can be either detrimental or beneficial. Ferroptosis can be effectively triggered in drug-resistant cancer cells in which ROS levels are often highly elevated. Key signaling pathways, including receptor tyrosine kinase (RTK), mitogen-activated protein kinase (MAPK), and nuclear factor erythroid 2-related factor 2 (NRF2), are promising targets for modulating ROS homeostasis and sensitizing cancer cells to ferroptosis. In this review, we discuss the molecular mechanisms governing ferroptosis, the interplay between ROS and ferroptosis resistance, and emerging therapeutic approaches designed to enhance ferroptosis induction in drug-resistant cancer cells. Altogether, a combination of ferroptosis inducers and conventional treatments may improve the therapeutic efficacy and help overcome resistance mechanisms.

Limited data exist regarding the real-world practices and clinical outcomes in patients with ischemic heart failure with reduced left ventricular ejection fractions (LVEFs).Using nationwide registry data from South Korea, we aimed to investigate long-term outcomes and clinical practices, especially implantable cardioverter defibrillators (ICDs) implantation, in patients with reduced LVEFs at least 40 days after acute myocardial infarction (AMI). Of 13,056 patients with AMI between 2011 and 2015, we analyzed 350 (median age, 66 years [interquartile range, 56-75]) who had LVEFs <40% on follow-up transthoracic echocardiogram 40 days after the index event. The primary outcome was cardiac-cause mortality at 3 years. Secondary outcomes comprised major cardiovascular events as well as outcomes defined by the use of ICDs, cardiac resynchronization therapy defibrillators (CRT-Ds), and electrophysiology studies. Among 350 patients, 39 (11.1%) died from cardiac causes during 3 years of follow-up. Eleven (3.1%) were hospitalized for ventricular tachycardia. The rate of ICD or CRT-D implantation up to 3 years was 5.7% (20/350). Cox time-to-event analysis revealed older age, LVEF <30%, diabetes mellitus, and previous MI or revascularization as positively associated with cardiac death, whereas the use of statins and body weight <67 kg were negatively associated. This nationwide Korean registry demonstrated that only 5.7% of patients who had reduced LVEFs after 40 days of AMI underwent ICD implantations over 3 years. Considering the high mortality, concerted efforts are needed to improve clinical outcomes for patients who may have been candidates for ICD implantation.

Background: The Act on Decisions on Life-Sustaining Treatment (LST) has been implemented in Korea since 2018, yet data on its application in neurocritical care units remain scarce. This study aimed to evaluate the clinical characteristics and outcomes of LST withdrawal or withholding in the neurocritical care unit. Methods: This study was a retrospective analysis conducted at a tertiary university hospital in Busan, South Korea. Among patients admitted to the neurocritical care unit between February 2018 and August 2023, those with documented decisions for LST withdrawal or withholding were enrolled. Demographic and clinical characteristics, underlying and combined conditions, reasons for LST decisions, measures taken, and time from LST withdrawal to death were extracted from medical records. Results: A total of 69 patients were included, with a median age of 67 years, and 38 (55%) were male. Cerebrovascular disease (62%) and traumatic brain injury (22%) were the most common underlying diagnoses. The primary reason for LST decisions was irreversible neurological damage (71%), followed by systemic complications (19%). Mechanical ventilation cessation (91%) and extubation (86%) were most frequently used measures for LST withdrawal. The median time from LST withdrawal to death was 22 minutes. Conclusions Our study demonstrates that LST decisions in the neurocritical care unit predominantly occur among patients with cerebrovascular disease or traumatic brain injury, mostly triggered by neurological deterioration. Most patients died shortly after withdrawal. These findings provide important insight into current LST withdrawal practices in neurocritical care and may assist clinical and ethical decision making in similar settings.

Background/Aims: Gastric antral vascular ectasia (GAVE) is a rare but important cause of gastrointestinal (GI) bleeding. The clinical course of GAVE is not well-known, and recurrent bleeding from GAVE is a therapeutic challenge. Therefore, we investigated the clinical course of GAVE and identified the risk factors for bleeding from it. Methods: We retrospectively reviewed the records of patients diagnosed with GAVE using upper GI endoscopy at Asan Medical Center between January 2004 and December 2019 and evaluated the clinical course and risk factors for bleeding from GAVE. Results: Of the 348 patients (mean age, 62.3 ± 10.7 years; male, 62%), bleeding from GAVE occurred in 123 (35%) patients during follow-up (median, 17.3 months; interquartile range [IQR], 4.2–46.6). GI bleeding from GAVE was significantly associated with Child–Pugh class B or C liver cirrhosis (odds ratio [OR], 2.55; 95% confidence interval [CI], 1.57–4.16), chronic kidney disease (CKD) (OR, 2.77; 95% CI, 1.52–5.07), use of antithrombotic agents (OR, 2.34; 95% CI, 1.13–4.82), and involvement of the duodenal bulb (OR, 3.21; 95% CI, 1.76–5.86). Rebleeding occurred in 39 of 123 patients (32%), in whom CKD (OR, 2.55; 95% CI, 1.12–5.81) was significantly associated with rebleeding. Endoscopic hemostasis was most commonly performed using argon plasma coagulation, and the median number of endoscopic hemostasis performed was 2 (IQR, 1–3). Conclusions A careful follow-up for bleeding is needed in GAVE patients with liver cirrhosis, CKD, use of antithrombotic agents, and duodenal bulb involvement.

Background: Perfluoroalkyl substances (PFAS) are used in various products, and PFAS have been detected in outdoor clothing. PFAS can be absorbed into the human body via oral ingestion, inhalation, and dermal contact. In this study, we examined the association between the frequency of using outdoor clothing and serum PFAS concentrations in the Korean population using data from cycle 4 (2018–2020) of the Korean National Environmental Health Survey. Methods: Data from 2,993 adult participants were analyzed. The participants were classified into low-concentration and high-concentration groups based on the 75th percentile concentration of serum PFAS. The use of outdoor clothing was categorized into three groups: non-use, <4 times a week, and ≥4 times a week. The odds ratio (OR) for serum PFAS levels associated with use of outdoor clothing was determined through logistic regression analysis, adjusted for demographic characteristics, health-related factors, PFAS-treated items, dietary factors, and ventilation time. Results: ORs for high serum PFAS were higher in groups using outdoor clothing compared to the non-user group. In males, the adjusted ORs for the < 4 times a week and ≥ 4 times a week outdoor clothing usage group were as follows: perfluorooctanoic acid (PFOA), 1.26 (95% confidence interval [CI]: 1.10–1.44) and 1.70 (1.40–2.07); perfluorohexanesulfonic acid (PFHxS), 1.49 (1.16–1.92) and 1.70 (1.22–2.37); and perfluorononanoic acid (PFNA), 1.34 (1.19–1.51) and 1.68 (1.38–2.05), respectively. In females, the respective ORs were as follows: PFOA 1.32 (95% CI: 1.19–1.46) and 1.53 (1.01–2.32); PFHxS, 1.46 (1.08–1.96) and 2.63 (2.10–3.29); PFNA, 1.38 (1.22–1.55) and 1.45 (1.07–1.96). Conclusions In adults, elevated serum PFAS levels were associated with increased frequency of using outdoor clothing.

Background/Aims: The Korean guidelines for Helicobacter pylori treatment were revised in 2020, however, the extent of adherence to these guidelines in clinical practice remains unclear. Herein, we initiated a prospective, nationwide, multicenter registry study in 2021 to evaluate the current management of H.pylori infection in Korea. Methods: This interim report describes the adherence to the revised guidelines and their impact on firstline eradication rates. Data on patient demographics, diagnoses, treatments, and eradication outcomes were collected using a web-based electronic case report form. Results: A total of 7,261 patients from 66 hospitals who received first-line treatment were analyzed.The modified intention-to-treat eradication rate for first-line treatment was 81.0%, with 80.4% of the prescriptions adhering to the revised guidelines. The most commonly prescribed regimen was the 14-day clarithromycin-based triple therapy (CTT; 42.0%), followed by tailored therapy (TT; 21.2%), 7-day CTT (14.1%), and 10-day concomitant therapy (CT; 10.1%). Time-trend analysis demonstrated significant increases in guideline adherence and the use of 10-day CT and TT, along with a decrease in the use of 7-day CTT (all p<0.001). Multivariate logistic regression analysis revealed that guideline adherence was significantly associated with first-line eradication success (odds ratio, 2.03; 95% confidence interval, 1.61 to 2.56; p<0.001). Conclusions The revised guidelines for the treatment of H. pylori infection have been increasingly adopted in routine clinical practice in Korea, which may have contributed to improved first-line eradication rates. Notably, the 14-day CTT, 10-day CT, and TT regimens are emerging as the preferred first-line treatment options among Korean physicians.

Purpose: This study investigated urinary incontinence (UI) following holmium laser enucleation of the prostate (HoLEP), based on the postoperative period, type of UI, and severity according to prostate volume. Methods: We analyzed prospectively collected data from patients who underwent HoLEP for benign prostatic hyperplasia at Seoul National University Hospital between January 2010 and June 2022. Patients were followed-up at 2 weeks, 3 months, and 6 months postoperatively. The patients were divided into 3 prostate volume groups: A (30–80 mL), B (81–120 mL), and C (>120 mL). We compared clinical outcomes and UI rates between the groups. Results: In total, 1,675 patients were included. The preoperative urgency UI (UUI) rate was 16.1%, with no significant difference between the groups (P=0.81). Two weeks postoperatively, the UUI rate was 6.0% (including a de novo UUI rate of 4.2%), with no significant differences between the groups. The stress UI (SUI) rate at 2 weeks postoperatively was 6.3%, and increased with larger prostate volume (P=0.04). The UUI and SUI rates decreased to 0.9% and 1.2%, respectively, 6 months postoperatively. Six months postoperatively, the SUI rate was significantly lower in group A (P=0.02), whereas the UUI rate did not differ between the groups (P=0.69). Conclusions Our results demonstrated that the preoperative UUI rate was high at baseline. Both the UUI and SUI rates continuously decreased up to 6 months postoperatively. Although the SUI rates significantly differed according to prostate volume, there was no significant difference in the UUI rate.

Irritable bowel syndrome (IBS) is a chronic, disabling, and functional bowel disorder that significantly affects social functioning and reduces quality of life and increases social costs. The Korean Society of Neurogastroenterology and Motility published clinical practice guidelines on the management of IBS based on a systematic review of the literature in 2017, and planned to revise these guidelines in light of new evidence on the pathophysiology, diagnosis, and management of IBS. The current revised version of the guidelines is consistent with the previous version and targets adults diagnosed with or suspected of having IBS. These guidelines were developed using a combination of de novo and adaptation methods, with analyses of existing guidelines and discussions within the committee, leading to the identification of key clinical questions. Finally, the guidelines consisted of 22 recommendations, including 3 concerning the definition and risk factors of IBS, 4 regarding diagnostic modalities and strategies, 2 regarding general management, and 13 regarding medical treatment. For each statement, the advantages, disadvantages, and precautions were thoroughly detailed. The modified Delphi method was used to achieve expert consensus to adopt the core recommendations of the guidelines. These guidelines serve as a reference for clinicians (including primary care physicians, general healthcare providers, medical students, residents, and other healthcare professionals) and patients, helping them to make informed decisions regarding IBS management.

Background: and Purpose Previous research on patients with acute ischemic stroke (AIS) has shown a 0.5% incidence of major gastrointestinal bleeding (GIB) requiring blood transfusion during hospitalization. The existing literature has insufficiently explored the long-term incidence in this population despite the decremental impact of GIB on stroke outcomes. Methods: We analyzed the data from a cohort of patients with AIS admitted to 14 hospitals as part of a nationwide multicenter prospective stroke registry between 2011 and 2013. These patients were followed up for up to 6 years. The occurrence of major GIB events, defined as GIB necessitating at least two units of blood transfusion, was tracked using the National Health Insurance Service claims data. Results: Among 10,818 patients with AIS (male, 59%; mean age, 68±13 years), 947 (8.8%) experienced 1,224 episodes of major GIB over a median follow-up duration of 3.1 years. Remarkably, 20% of 947 patients experienced multiple episodes of major GIB. The incidence peaked in the first month after AIS, reaching 19.2 per 100 person-years, and gradually decreased to approximately one-sixth of this rate by the 2nd year with subsequent stabilization. Multivariable analysis identified the following predictors of major GIB: anemia, estimated glomerular filtration rate <60 mL/min/1.73 m2 , and a 3-month modified Rankin Scale score of ≥4. Conclusion Patients with AIS are susceptible to major GIB, particularly in the first month after the onset of AIS, with the risk decreasing thereafter. Implementing preventive strategies may be important, especially for patients with anemia and impaired renal function at stroke onset and those with a disabling stroke.