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.

Background and Objectives: Several real-world studies have been done in patients with nonvalvular atrial fibrillation (NVAF); however, information on its safety profile in patients with renal impairment is limited. XARENAL, a real-world study, aimed to prospectively investigate the safety profile of rivaroxaban in patients with NVAF with renal impairment (creatinine clearance [CrCl], 15–49 mL/min). Methods: XARENAL is an observational single-arm cohort study in renal impairment NVAF patients. Patients were followed up approximately every 3 months for 1 year or until 30 days following early discontinuation. The primary endpoint was major bleeding events. All adverse events, symptomatic thromboembolic events, treatment duration, and renal function change from baseline were the secondary endpoints. Results: XARENAL included 888 patients from 29 study sites. Overall, 713 (80.3%) had moderate renal impairment (CrCl, 30–49 mL/min), and 175 (19.7%) had severe renal impairment (CrCl, 15–29 mL/min) with a mean estimated glomerular filtration rate (eGFR) of 45.2±13.0 mL/min/1.73 m 2 . The mean risk scores were 3.3±1.4 and 1.7±0.9 for CHA 2 DS 2 -VASc score and HAS-BLED score, respectively. An incidence proportion of 5.6% (6.2 events per 100 patient-years) developed major bleeding; however, fatal bleeding occurred in 0.5% (0.5 events per 100 patient-years). The mean change in the eGFR was 2.22±26.47 mL/min/1.73 m 2 per year. Conclusions XARENAL observed no meaningful differences in major bleeding events from other previous findings as well as renal function changes in rivaroxaban-treated NVAF patients with renal impairment, which is considered to be acceptable in clinical practice.

Background and Objectives: Several real-world studies have been done in patients with nonvalvular atrial fibrillation (NVAF); however, information on its safety profile in patients with renal impairment is limited. XARENAL, a real-world study, aimed to prospectively investigate the safety profile of rivaroxaban in patients with NVAF with renal impairment (creatinine clearance [CrCl], 15–49 mL/min). Methods: XARENAL is an observational single-arm cohort study in renal impairment NVAF patients. Patients were followed up approximately every 3 months for 1 year or until 30 days following early discontinuation. The primary endpoint was major bleeding events. All adverse events, symptomatic thromboembolic events, treatment duration, and renal function change from baseline were the secondary endpoints. Results: XARENAL included 888 patients from 29 study sites. Overall, 713 (80.3%) had moderate renal impairment (CrCl, 30–49 mL/min), and 175 (19.7%) had severe renal impairment (CrCl, 15–29 mL/min) with a mean estimated glomerular filtration rate (eGFR) of 45.2±13.0 mL/min/1.73 m 2 . The mean risk scores were 3.3±1.4 and 1.7±0.9 for CHA 2 DS 2 -VASc score and HAS-BLED score, respectively. An incidence proportion of 5.6% (6.2 events per 100 patient-years) developed major bleeding; however, fatal bleeding occurred in 0.5% (0.5 events per 100 patient-years). The mean change in the eGFR was 2.22±26.47 mL/min/1.73 m 2 per year. Conclusions XARENAL observed no meaningful differences in major bleeding events from other previous findings as well as renal function changes in rivaroxaban-treated NVAF patients with renal impairment, which is considered to be acceptable in clinical practice.

Objective: Using a nationally representative cohort of medical claims data in Korea, this study aimed to analyze the association between the use of various anti-rheumatic agents and the risk of acute myocardial infarction (AMI) in patients with rheumatoid arthritis (RA). Methods: This nested case-control study used the Korean Health Insurance Review and Assessment data of 35,133 patients newly diagnosed with RA between 2011 and 2020. Incident AMI patients were identified and matched at a 1:4 ratio with randomly selected controls. The usage of anti-rheumatic agents was measured from the date of RA diagnosis to the index date and stratified based on exposure time and duration. The risk of AMI associated with each anti-rheumatic agent was estimated using conditional logistic regression, adjusted for comorbidities and concomitant drug use. Results: Of the 35,133 patients with RA, 484 were diagnosed with AMI. In total, 484 AMI patients and 1,924 controls with newly diagnosed RA were included in the analysis. Current exposure and long-term exposure to glucocorticoids (adjusted odds ratio [aOR]: 2.301, 95% confidence interval [CI]: 1.741~3.041; aOR: 1.792, 95% CI: 1.378~2.330) and leflunomide (aOR: 1.525, 95% CI: 1.196~1.944; aOR: 1.740, 95% CI: 1.372~2.207) were associated with an increased risk of AMI. Conclusion The study demonstrates a significant association between the current and long-term use of glucocorticoids and leflunomide and an increased risk of AMI in patients with RA. These findings underscore the importance of careful consideration of cardiovascular risks when selecting anti-rheumatic agents for RA treatment.

Background: This study aimed to report the radiological outcomes and risk factors for malalignment of fractures in the distal onefourth of the tibia treated with intramedullary nailing via the infrapatellar approach. Methods: This study retrospectively analyzed 60 patients (37 men and 23 women; mean age, 45.4 years) who had distal onefourth tibial fractures and were treated with intramedullary nailing using the infrapatellar approach. These patients were treated between January 2009 and December 2021, with a minimum follow-up of 1 year. Fractures were classified according to the Arbeitsgemeinschaft für Osteosynthesefragen/Orthopaedic Trauma Association system: 25 were type 42A, 30 were type 42B, and 5 were type 43A. Radiographic outcomes focused on bone union and malalignment, defined as a valgus deviation greater than 5° compared to the unaffected side. Potential risk factors for malalignment, including open fractures (9 cases, 15%), distal tibial extension (20 cases, 33%), and distal fibular fractures (24 cases, 40%), were documented. Results: Bone union was achieved in all cases, with an average duration of 3.2 months (range, 3–5 months). No cases of postoperative wound infection or neurovascular damage were observed. The average coronal plane malalignment was 2.6° of valgus (range, 0°–9.3°), with significant malalignment (over 5°) occurring in 5 patients (8.3%). Comparison of the malalignment (n = 5) and normal (n = 55) groups showed a statistically significant difference in distal bone fragment length (average, 66.5 mm vs. 77.2 mm;p = 0.008) but no significant differences in other variables. A change-point analysis revealed that cases with a primary fracture line < 65 mm showed 4.5° of coronal malalignment, while those with > 65 mm showed 2.3°; the difference was statistically significant (p = 0.01). Conclusions Intramedullary nailing using the infrapatellar approach for distal one-fourth tibial fractures results in successful bone union with a low incidence of valgus malalignment. However, careful attention is necessary to prevent angular deformities, especially when the distal fragment is short.

Background: This study aimed to report the radiological outcomes and risk factors for malalignment of fractures in the distal onefourth of the tibia treated with intramedullary nailing via the infrapatellar approach. Methods: This study retrospectively analyzed 60 patients (37 men and 23 women; mean age, 45.4 years) who had distal onefourth tibial fractures and were treated with intramedullary nailing using the infrapatellar approach. These patients were treated between January 2009 and December 2021, with a minimum follow-up of 1 year. Fractures were classified according to the Arbeitsgemeinschaft für Osteosynthesefragen/Orthopaedic Trauma Association system: 25 were type 42A, 30 were type 42B, and 5 were type 43A. Radiographic outcomes focused on bone union and malalignment, defined as a valgus deviation greater than 5° compared to the unaffected side. Potential risk factors for malalignment, including open fractures (9 cases, 15%), distal tibial extension (20 cases, 33%), and distal fibular fractures (24 cases, 40%), were documented. Results: Bone union was achieved in all cases, with an average duration of 3.2 months (range, 3–5 months). No cases of postoperative wound infection or neurovascular damage were observed. The average coronal plane malalignment was 2.6° of valgus (range, 0°–9.3°), with significant malalignment (over 5°) occurring in 5 patients (8.3%). Comparison of the malalignment (n = 5) and normal (n = 55) groups showed a statistically significant difference in distal bone fragment length (average, 66.5 mm vs. 77.2 mm;p = 0.008) but no significant differences in other variables. A change-point analysis revealed that cases with a primary fracture line < 65 mm showed 4.5° of coronal malalignment, while those with > 65 mm showed 2.3°; the difference was statistically significant (p = 0.01). Conclusions Intramedullary nailing using the infrapatellar approach for distal one-fourth tibial fractures results in successful bone union with a low incidence of valgus malalignment. However, careful attention is necessary to prevent angular deformities, especially when the distal fragment is short.

Background: This study aimed to report the radiological outcomes and risk factors for malalignment of fractures in the distal onefourth of the tibia treated with intramedullary nailing via the infrapatellar approach. Methods: This study retrospectively analyzed 60 patients (37 men and 23 women; mean age, 45.4 years) who had distal onefourth tibial fractures and were treated with intramedullary nailing using the infrapatellar approach. These patients were treated between January 2009 and December 2021, with a minimum follow-up of 1 year. Fractures were classified according to the Arbeitsgemeinschaft für Osteosynthesefragen/Orthopaedic Trauma Association system: 25 were type 42A, 30 were type 42B, and 5 were type 43A. Radiographic outcomes focused on bone union and malalignment, defined as a valgus deviation greater than 5° compared to the unaffected side. Potential risk factors for malalignment, including open fractures (9 cases, 15%), distal tibial extension (20 cases, 33%), and distal fibular fractures (24 cases, 40%), were documented. Results: Bone union was achieved in all cases, with an average duration of 3.2 months (range, 3–5 months). No cases of postoperative wound infection or neurovascular damage were observed. The average coronal plane malalignment was 2.6° of valgus (range, 0°–9.3°), with significant malalignment (over 5°) occurring in 5 patients (8.3%). Comparison of the malalignment (n = 5) and normal (n = 55) groups showed a statistically significant difference in distal bone fragment length (average, 66.5 mm vs. 77.2 mm;p = 0.008) but no significant differences in other variables. A change-point analysis revealed that cases with a primary fracture line < 65 mm showed 4.5° of coronal malalignment, while those with > 65 mm showed 2.3°; the difference was statistically significant (p = 0.01). Conclusions Intramedullary nailing using the infrapatellar approach for distal one-fourth tibial fractures results in successful bone union with a low incidence of valgus malalignment. However, careful attention is necessary to prevent angular deformities, especially when the distal fragment is short.

Objective: Using a nationally representative cohort of medical claims data in Korea, this study aimed to analyze the association between the use of various anti-rheumatic agents and the risk of acute myocardial infarction (AMI) in patients with rheumatoid arthritis (RA). Methods: This nested case-control study used the Korean Health Insurance Review and Assessment data of 35,133 patients newly diagnosed with RA between 2011 and 2020. Incident AMI patients were identified and matched at a 1:4 ratio with randomly selected controls. The usage of anti-rheumatic agents was measured from the date of RA diagnosis to the index date and stratified based on exposure time and duration. The risk of AMI associated with each anti-rheumatic agent was estimated using conditional logistic regression, adjusted for comorbidities and concomitant drug use. Results: Of the 35,133 patients with RA, 484 were diagnosed with AMI. In total, 484 AMI patients and 1,924 controls with newly diagnosed RA were included in the analysis. Current exposure and long-term exposure to glucocorticoids (adjusted odds ratio [aOR]: 2.301, 95% confidence interval [CI]: 1.741~3.041; aOR: 1.792, 95% CI: 1.378~2.330) and leflunomide (aOR: 1.525, 95% CI: 1.196~1.944; aOR: 1.740, 95% CI: 1.372~2.207) were associated with an increased risk of AMI. Conclusion The study demonstrates a significant association between the current and long-term use of glucocorticoids and leflunomide and an increased risk of AMI in patients with RA. These findings underscore the importance of careful consideration of cardiovascular risks when selecting anti-rheumatic agents for RA 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.