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.

Radiation-induced cavernous malformations (RICMs) are rare but significant late complications of highdose radiation therapy, particularly in young survivors of brain tumors. This report presents two cases of RICMs following aggressive multimodal treatment, including surgery, chemotherapy, and radiation therapy. Case 1 was a 22-year-old male patient with medulloblastoma treated with craniospinal irradiation, tumor bed boost, and tandem autologous peripheral blood stem cell transplantation. Approximately 8 years after treatment completion, routine follow-up imaging revealed a small focal hemorrhage in the right cerebellum, consistent with an RICM. The lesion was asymptomatic and managed conservatively with regular imaging, showing spontaneous resolution over time, with a significant size reduction noted 9 years post-treatment. Case 2 describes a 32-year-old male with an intracranial germinoma treated with whole-ventricular irradiation. Three years after treatment, the patient developed a symptomatic hemorrhagic RICM near a pre-existing developmental venous anomaly. Surgical resection and Gamma Knife Surgery stabilized the lesion; however, residual symptoms, including tremors and gait disturbances, persisted, affecting the patient’s daily activities. These cases illustrate the diverse clinical courses of RICMs, ranging from spontaneous resolution to the necessity of surgical intervention, and emphasize the importance of long-term surveillance and tailored management strategies for late-onset complications.

Background: This study analyzed the epidemiology and treatment outcomes of germ cell tumorpatients at a single institution. Methods: A retrospective analysis was conducted on intracranial germ cell tumor (iGCT) pa-tients treated at a single tertiary hospital from 2004 to 2019. Patients were categorized based on treatment modality: Korean Society for Pediatric Neuro-Oncology (KSPNO) protocol or bleomycin, etoposide, and cisplatin with radiation therapy. Results: Forty-nine iGCT patients treated with combined chemotherapy and radiotherapywere analyzed. The median age was 19 years (range: 6–40), with a median follow-up duration of 148.0 months (range: 10.5–265.5). Tumors were most common in the pineal gland (51.0%). Although no significant differences in outcomes were observed between treatment modalities, outcomes varied significantly by pathological type. The 10-year progression-free survival rates for germinoma and non-germinomatous germ cell tumors (NGGCTs) were 88.1% and 32.7%, respectively (p=0.003), while the 10-year overall survival rates were 92.9% and 67.5%, respectively (p<0.001). Fourteen patients experienced CTCAE (Common Terminology Criteria for Adverse Events) grade ≥3 adverse events, with one eventrelated death. Conclusion Pure germinoma demonstrated higher survival and lower recurrence rates comparedto NGGCT. The KSPNO protocol appears to be an acceptable and safe treatment option for iGCT patients. Further multi-institutional studies with larger cohorts are warranted.

Purpose: The metabolism of tamoxifen is influenced by various cytochrome p450 enzymes, including CYP2D6 and CYP2C19, leading to variations in the levels of endoxifen, even with the same tamoxifen dose. However, the clinical significance of endoxifen for the prognosis of breast cancer patients remains controversial. This study aimed to elucidate the relevance of endoxifen level to recurrence-free survival censored with tamoxifen discontinuation (RFSt), representing the RFS for tamoxifen itself, of breast cancer patients and determine a suitable cutoff for prognostication. Materials and Methods: The study included 478 breast cancer patients. Tamoxifen and its metabolites, including endoxifen, were measured using liquid chromatography-tandem mass spectrometry. An optimal cutoff was determined with maximally selected rank statistics. Survival analysis and Cox regression were conducted based on this cutoff. Results: An endoxifen level of 21.00 ng/mL was the optimal cutoff for prognostication. Survival analysis revealed a statistically significant difference in RFSt between the low endoxifen group (≤ 21.00 ng/mL) and the high endoxifen group (> 21.00 ng/mL) (log-rank test, p=0.032). The 10-year probability of RFSt was 83.2% (95% confidence interval [CI], 77.0 to 89.9) and 88.3% (95% CI, 83.3 to 93.5) in the low and high endoxifen groups, respectively. Multivariable Cox proportional hazards regression indicated endoxifen concentration as a significant factor associated with prognosis. Conclusion Endoxifen could serve as a marker for appropriate tamoxifen treatment with a cutoff of 21.00 ng/mL. Based on this cutoff, therapeutic drug monitoring would benefit patients displaying suboptimal endoxifen concentrations.

Background: and Purpose To determine the clinical phenotypes, relapse timing, treatment responses, and outcomes of children with relapsing myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Methods: We collected the demographic, clinical, laboratory, and radiological data of patients aged <18 years who had been diagnosed with MOGAD at Seoul National University Children’s Hospital between January 2010 and January 2022; 100 were identified as positive for MOG antibodies, 43 of whom experienced relapse. Results: The median age at onset was 7 years (range 2–16 years). The median number of relapses was 2 (range 1–8), and patients were followed up for a median of 65 months (range 5–214 months). The first relapse was experienced before 3 months from onset by 15 patients (34.9%). The most-common initial phenotypes were acute disseminated encephalomyelitis (n=17, 39.5%) and optic neuritis (ON; n=11, 25.6%). The most-common relapse phenotypes were neuromyelitis optica spectrum disorder (n=9, 20.9%), relapsing ON (n=6, 14.0%), and multiphasic disseminated encephalomyelitis (n=6, 14.0%). Many of the patients (n=18, 41.9%) were not specifically categorized. A high proportion of these patients had non-acute disseminated encephalomyelitis encephalitis. Atypical phenotypes such as prolonged fever or hemiplegic migraine-like episodes were also noted. Mycophenolate mofetil and cyclic immunoglobulin treatment significantly reduced the annual relapse rates. Conclusions Our 43 pediatric patients with relapsing MOGAD showed a tendency toward early relapse and various relapse phenotypes. The overall prognoses of these patients were good regardless of phenotype or response to second-line immunosuppressant treatment.

Radiation-induced cavernous malformations (RICMs) are rare but significant late complications of highdose radiation therapy, particularly in young survivors of brain tumors. This report presents two cases of RICMs following aggressive multimodal treatment, including surgery, chemotherapy, and radiation therapy. Case 1 was a 22-year-old male patient with medulloblastoma treated with craniospinal irradiation, tumor bed boost, and tandem autologous peripheral blood stem cell transplantation. Approximately 8 years after treatment completion, routine follow-up imaging revealed a small focal hemorrhage in the right cerebellum, consistent with an RICM. The lesion was asymptomatic and managed conservatively with regular imaging, showing spontaneous resolution over time, with a significant size reduction noted 9 years post-treatment. Case 2 describes a 32-year-old male with an intracranial germinoma treated with whole-ventricular irradiation. Three years after treatment, the patient developed a symptomatic hemorrhagic RICM near a pre-existing developmental venous anomaly. Surgical resection and Gamma Knife Surgery stabilized the lesion; however, residual symptoms, including tremors and gait disturbances, persisted, affecting the patient’s daily activities. These cases illustrate the diverse clinical courses of RICMs, ranging from spontaneous resolution to the necessity of surgical intervention, and emphasize the importance of long-term surveillance and tailored management strategies for late-onset complications.

Background: This study analyzed the epidemiology and treatment outcomes of germ cell tumorpatients at a single institution. Methods: A retrospective analysis was conducted on intracranial germ cell tumor (iGCT) pa-tients treated at a single tertiary hospital from 2004 to 2019. Patients were categorized based on treatment modality: Korean Society for Pediatric Neuro-Oncology (KSPNO) protocol or bleomycin, etoposide, and cisplatin with radiation therapy. Results: Forty-nine iGCT patients treated with combined chemotherapy and radiotherapywere analyzed. The median age was 19 years (range: 6–40), with a median follow-up duration of 148.0 months (range: 10.5–265.5). Tumors were most common in the pineal gland (51.0%). Although no significant differences in outcomes were observed between treatment modalities, outcomes varied significantly by pathological type. The 10-year progression-free survival rates for germinoma and non-germinomatous germ cell tumors (NGGCTs) were 88.1% and 32.7%, respectively (p=0.003), while the 10-year overall survival rates were 92.9% and 67.5%, respectively (p<0.001). Fourteen patients experienced CTCAE (Common Terminology Criteria for Adverse Events) grade ≥3 adverse events, with one eventrelated death. Conclusion Pure germinoma demonstrated higher survival and lower recurrence rates comparedto NGGCT. The KSPNO protocol appears to be an acceptable and safe treatment option for iGCT patients. Further multi-institutional studies with larger cohorts are warranted.

Purpose: The metabolism of tamoxifen is influenced by various cytochrome p450 enzymes, including CYP2D6 and CYP2C19, leading to variations in the levels of endoxifen, even with the same tamoxifen dose. However, the clinical significance of endoxifen for the prognosis of breast cancer patients remains controversial. This study aimed to elucidate the relevance of endoxifen level to recurrence-free survival censored with tamoxifen discontinuation (RFSt), representing the RFS for tamoxifen itself, of breast cancer patients and determine a suitable cutoff for prognostication. Materials and Methods: The study included 478 breast cancer patients. Tamoxifen and its metabolites, including endoxifen, were measured using liquid chromatography-tandem mass spectrometry. An optimal cutoff was determined with maximally selected rank statistics. Survival analysis and Cox regression were conducted based on this cutoff. Results: An endoxifen level of 21.00 ng/mL was the optimal cutoff for prognostication. Survival analysis revealed a statistically significant difference in RFSt between the low endoxifen group (≤ 21.00 ng/mL) and the high endoxifen group (> 21.00 ng/mL) (log-rank test, p=0.032). The 10-year probability of RFSt was 83.2% (95% confidence interval [CI], 77.0 to 89.9) and 88.3% (95% CI, 83.3 to 93.5) in the low and high endoxifen groups, respectively. Multivariable Cox proportional hazards regression indicated endoxifen concentration as a significant factor associated with prognosis. Conclusion Endoxifen could serve as a marker for appropriate tamoxifen treatment with a cutoff of 21.00 ng/mL. Based on this cutoff, therapeutic drug monitoring would benefit patients displaying suboptimal endoxifen concentrations.

Background: and Purpose To determine the clinical phenotypes, relapse timing, treatment responses, and outcomes of children with relapsing myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Methods: We collected the demographic, clinical, laboratory, and radiological data of patients aged <18 years who had been diagnosed with MOGAD at Seoul National University Children’s Hospital between January 2010 and January 2022; 100 were identified as positive for MOG antibodies, 43 of whom experienced relapse. Results: The median age at onset was 7 years (range 2–16 years). The median number of relapses was 2 (range 1–8), and patients were followed up for a median of 65 months (range 5–214 months). The first relapse was experienced before 3 months from onset by 15 patients (34.9%). The most-common initial phenotypes were acute disseminated encephalomyelitis (n=17, 39.5%) and optic neuritis (ON; n=11, 25.6%). The most-common relapse phenotypes were neuromyelitis optica spectrum disorder (n=9, 20.9%), relapsing ON (n=6, 14.0%), and multiphasic disseminated encephalomyelitis (n=6, 14.0%). Many of the patients (n=18, 41.9%) were not specifically categorized. A high proportion of these patients had non-acute disseminated encephalomyelitis encephalitis. Atypical phenotypes such as prolonged fever or hemiplegic migraine-like episodes were also noted. Mycophenolate mofetil and cyclic immunoglobulin treatment significantly reduced the annual relapse rates. Conclusions Our 43 pediatric patients with relapsing MOGAD showed a tendency toward early relapse and various relapse phenotypes. The overall prognoses of these patients were good regardless of phenotype or response to second-line immunosuppressant treatment.

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.