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.

Background: and Purpose The Treat Stroke to Target (TST) was a randomized clinical trial involving French and Korean patients demonstrating that a lower low-density lipoprotein cholesterol (LDL-C, <70 mg/dL) target group (LT) experienced fewer cerebro-cardiovascular events than a higher target (90–110 mg/dL) group (HT). However, whether these results can be applied to Asian patients with different ischemic stroke subtypes remains unclear. Methods: Patients from 14 South Korean centers were analyzed separately. Patients with ischemic stroke or transient ischemic attack with evidence of atherosclerosis were randomized into LT and HT groups. The primary endpoint was a composite of ischemic stroke, myocardial infarction, coronary or cerebral revascularization, and cardiovascular death. Results: Among 712 enrolled patients, the mean LDL-C level was 71.0 mg/dL in 357 LT patients and 86.1 mg/dL in 355 HT patients. The primary endpoint occurred in 24 (6.7%) of LT and in 31 (8.7%) of HT group patients (adjusted hazard ratio [HR]=0.78; 95% confidence interval [CI]=0.45–1.33, P=0.353). Cardiovascular events alone occurred significantly less frequently in the LT than in the HT group (HR 0.26, 95% CI 0.09–0.80, P=0.019), whereas there were no significant differences in ischemic stroke events (HR 1.12, 95% CI 0.60–2.10, P=0.712). The benefit of LT was less apparent in patients with small vessel disease and intracranial atherosclerosis than in those with extracranial atherosclerosis. Conclusion In contrast to the French TST, the outcomes in Korean patients were neutral. Although LT was more effective in preventing cardiovascular diseases, it was not so in stroke prevention, probably attributed to the differences in stroke subtypes. Further studies are needed to elucidate the efficacy of statins and appropriate LDL-C targets in Asian patients with stroke.

Purpose: To evaluate the characteristics, anatomical success rate, and factors that may affect the anatomical success of rhegmatogenous retinal detachment in patients in their 20s. Methods: We retrospectively analyzed the medical records of patients aged 20-29 years who underwent surgery for rhegmatogenous retinal detachment from January 2018 to December 2022. We examined factors such as sex, age, duration of illness, preoperative best corrected visual acuity, presence of underlying diseases, proliferative vitreoretinopathy, lattice degeneration, macular involvement, extent of retinal detachment at diagnosis, axial length, and myopia level to explore their impact on surgical outcomes. Results: The study included 122 eyes. The mean age was 23.81 ± 2.82 years, and the average sphere power was -5.80 ± 3.71 diopters (D). The percentage of eyes with a refraction of ≤ -6.0 D came to 44.3% (54/122), and with ≤ -4.0 D it amounted to 72.1% (88/122). The average logarithm of the minimum angle of resolution (logMAR) best corrected visual acuity improved significantly from 0.52 ± 0.68 before surgery to 0.28 ± 0.45 after surgery. The primary surgical success rates were 92.0% for scleral buckling, 88.9% for vitrectomy, and 92.3% for combined scleral buckling and vitrectomy, with no significant factors related to anatomical success identified. Conclusions There was a high prevalence of moderate to severe myopia among patients in their 20s with rhegmatogenous retinal detachment. However, no statistically significant correlation was found between the degree of myopia and anatomical success. Both functional and anatomical outcomes were generally favorable in these patients.

Background and Objectives: Metoclopramide is an antagonist of dopamine D2 receptor and is capable of alleviating chemotherapy-induced nausea and vomiting. However, its underlying mechanisms and function in improving the efficiency of chemotherapy are not fully understood. In this study, we investigated the sensitizing effect of metoclopramide on the platinum-based drugs-mediated apoptosis in human head and neck cancer cells.Subjects and Method Apoptosis was analyzed using a cell-based cytometer. The protein expression and messenger ribonucleic acid (mRNA) levels were assessed by Western blotting and real-time polymerase chain reaction, respectively. Results: Metoclopramide sensitized the platinum-based drug (cisplatin and oxaliplatin)-mediated apoptosis in AMC-HN4 cells, but not in normal cells. Mechanistically, we found that metoclopramide decreased Mcl-1 protein expression through post-translational regulation. Moreover, the overexpression of Mcl-1 prevented apoptosis by combined treatment of metoclopramide and platinum-based drugs. Conclusion Metoclopramide induced proteasome-mediated Mcl-1 downregulation, resulting in increased sensitivity to platinum-based drugs.

Objective: To assess the performance of novel qualitative diagnostic criteria using dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) to identify the pathologic complete response (pCR) of primary tumors in esophageal cancer after neoadjuvant chemoradiation (nCRT). Materials and Methods: Patients who underwent nCRT, subsequent MRI, positron emission tomography/computed tomography (PET/CT), endoscopy, or esophagectomy for esophageal cancer between October 2021 and October 2023 were retrospectively analyzed. The DCE-MRI response of primary tumors was interpreted using five grades by thoracic radiologists as follows: G1 (compatible with CR), G2 (probable CR), G3 (probable partial response [PR]), G4 (compatible with PR), and G5 (stable or progressive disease). The performances of MRI, PET/CT, endoscopy, and their combinations in diagnosing pCR in primary tumors were calculated. Results: A total of 52 patients (male:female, 46:6; age, 61.2 ± 8.0 years) were included. Surgical specimens revealed pCR (ypT0) in 34 patients. G1 as the MRI criterion for pCR of primary tumors yielded a positive predictive value (PPV), specificity of 100% (18/18), and low sensitivity (23.5% [8/34]). Combining G1 and G2 as the MRI criteria increased the sensitivity to 73.5% (25/34), with a specificity of 88.9% (16/18), accuracy of 78.8% (41/52), and PPV of 92.6% (25/27). Adding the DCEMRI results (G1-2) significantly improved accuracy for both PET/CT (from 65.4% [34/52] to 80.8% [42/52], P = 0.03) and endoscopy (from 55.8% [29/52] to 76.9% [40/52], P = 0.005), with increase in sensitivity (from 55.9% [19/34] to 82.4% [28/34] for PET/CT-based evaluation [P = 0.008] and from 47.1% [16/34] to 82.4% [28/34] for endoscopy-based evaluation [P = 0.001]). Conclusion DCE-MRI-based grading shows high diagnostic performance for identifying pCR in primary tumors, particularly in terms of PPV and specificity, and enhances response evaluation when combined with PET/CT and endoscopy.

Background: and Purpose This study was an open-label, dose-escalation, phase 1 clinical trial to determine the safety and dose of EN001 for patients with Duchenne muscular dystrophy (DMD). EN001, developed by ENCell, are allogeneic early-passage Wharton’s jelly-derived mesenchymal stem cells that originate at the umbilical cord, with preclinical studies demonstrating their high therapeutic efficacy for DMD. Methods: This phase 1 clinical trial explored the safety and tolerability of EN001 as a potential treatment option for patients with DMD. Six pediatric participants with DMD were divided into two subgroups of equal size: low-dose EN001 (5.0×105 cells/kg) and high-dose EN001 (2.5×106 cells/kg). All participants were monitored for 12 weeks after EN001 administration to assess its safety. Dose-limiting toxicity (DLT) was evaluated across 2 weeks post administration. Exploratory efficacy was evaluated by measuring serum creatine kinase levels, and functional evaluations—including spirometry, myometry, the North Star Ambulatory Assessment, and the 6-minute walk test—were conducted at week 12 and compared with the baseline values. Results: No participants experienced serious adverse events related to EN001 injection during the 12-week follow-up period. Mild adverse events included injection-related local erythema, edema, parosmia, and headache, but DLT was not observed. Functional evaluations at week 12 revealed no significant changes from baseline. Conclusions These results demonstrated that EN001 are safe and well tolerated for patients with DMD, and did not cause serious adverse events. The efficacy of EN001 could be confirmed through larger-scale future studies that incorporate repeated dosing and have a randomized controlled trial design.

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.

Background: and Purpose The pain lateralization in cluster headache (CH) may be related to the asymmetry in the functions of the brain hemispheres. The right-sided dominance of pain in CH has been found inconsistently across studies, and so we aimed to characterize this and identify the factors influencing pain lateralization during current and previous bouts. Methods: This study enrolled 227 patients from the Korean Cluster Headache Registry between October 2018 and December 2020. We evaluated the side of pain during current and previous bouts, demographic features, and clinical characteristics, including handedness. Multivariable logistic regression analyses were performed to identify factors associated with the side of pain. Results: The 227 patients with CH included 131 (57.7%) with right-sided pain and 86 (37.9%) with left-sided pain during the current bout (p<0.001). The 189 patients with previous bouts of CH included 86.8% who consistently reported the same side of pain throughout multiple bouts (side-locked pain), with a higher prevalence of pain on the right than the left side (55.0% vs. 31.7%, p<0.001). Multivariable analyses revealed that higher age at diagnosis (odds ratio [OR]=1.045, p=0.031) and shorter CH attacks (OR=0.992, p=0.017) were associated with left-side-locked pain. However, handedness was not associated with the lateralization of leftside-locked pain. Conclusions This study has confirmed the predominance of right-sided pain throughout multiple CH bouts. We found that higher age at diagnosis and shorter CH attacks were associated with left-side-locked pain, suggesting that certain clinical factors are associated with the pain laterality. However, the underlying mechanisms linking these factors to lateralized pain remain unclear and therefore require further investigation.