Objective: Although high-density lipoprotein cholesterol (HDL-C) is inversely associated with hematologic malignancies, modification by smoking has not been reported. We investigated how smoking and menopausal status modify these association. Methods: This population-based cohort study enrolled cancer-free individuals who underwent a national cancer screening in 2010 and followed up until December 2017. HDL-C levels were classified into eight groups based on 10 mg/dL intervals: (<30, 30–39, 40–49, 50–59, 60–69, 70–79, 80–89, or ≥90 mg/dL). Results: Among 4,517,892 participants, 5887 had lymphoma, 3348 had leukemia, and 12151 had unspecified hematologic malignancies. The adjusted hazard ratios (aHRs) for the lowest HDL-C levels compared to the 70–79 mg/dL range were 1.83 (1.45–2.31) for lymphoma, 3.14 (2.41–4.08) for leukemia, and 2.34 (2.01–2.72) for unspecified hematologic malignancy.The effects of low HDL-C levels on hematologic malignancies were similar in both men and women. Low HDL-C levels were associated with a higher risk of leukemia regardless of smoking status, but extremely high HDL-C levels were linked to a higher risk of leukemia (aHR, 2.32; 95% confidence interval [95% CI], 1.18–4.55) only in current smokers.The hazardous effect of low HDL-C levels on lymphoma was significant only in never smokers (aHR, 2.01; 95% CI, 1.51–2.68). Hazardous effects of low HDL-C levels on leukemia were observed only in post-menopausal women (aHR, 2.94; 95% CI, 1.69–5.11). Conclusion Low HDL-C levels were associated with a higher risk of leukemia and lymphoma, with discrepancies based on smoking and menopausal status.

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: Evidence remains limited on the real-world prescription of very low-dose oral anticoagulation among frail patients with atrial fibrillation (AF). We described the practice patterns, effectiveness, and safety of very low-dose edoxaban (15 mg once daily). Methods: Patients with AF prescribed edoxaban 15 mg once daily in 2 tertiary hospitals between 2016 and September 2022 were included. Baseline clinical characteristics and clinical outcomes of interest were thromboembolic and bleeding events. Results: A total of 674 patients were included (mean age 78.3±9.1, 49.7% aged ≥80 years, 49.3% women, median follow-up 1.0±1.2 years). Mean CHA 2 DS 2 -VASc score was 3.9±1.6, and the modified HAS-BLED score was 2.0±1.1. Between 2016 and 2022, the number of very lowdose edoxaban prescriptions increased. The main reasons for the prescription of very lowdose were low body weight (55.5% below 60 kg), anaemia (62.8%), chronic kidney disease (40.2%), active cancer (15.3%), concomitant anti-platelet use (26.7%), and prior major bleeding (19.7%). During a median follow-up duration of 8 (interquartile range 3–16) months, overall thromboembolic and bleeding events occurred in 16 (2.3%) and 88 (13.1%) patients, respectively. Compared to the expected event rates on the established risk scoring systems, patients receiving very low-dose edoxaban demonstrated a 61% reduction in ischemic stroke, a 68% reduction of ischemic stroke/transient ischemic attack/systemic embolism, whereas a 49% increase in major bleeding. Conclusions The prescription of very low-dose edoxaban was increased over time, attributable to various clinical factors. The use of very low-dose edoxaban reduced the expected risk of thromboembolic events.

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: Evidence remains limited on the real-world prescription of very low-dose oral anticoagulation among frail patients with atrial fibrillation (AF). We described the practice patterns, effectiveness, and safety of very low-dose edoxaban (15 mg once daily). Methods: Patients with AF prescribed edoxaban 15 mg once daily in 2 tertiary hospitals between 2016 and September 2022 were included. Baseline clinical characteristics and clinical outcomes of interest were thromboembolic and bleeding events. Results: A total of 674 patients were included (mean age 78.3±9.1, 49.7% aged ≥80 years, 49.3% women, median follow-up 1.0±1.2 years). Mean CHA 2 DS 2 -VASc score was 3.9±1.6, and the modified HAS-BLED score was 2.0±1.1. Between 2016 and 2022, the number of very lowdose edoxaban prescriptions increased. The main reasons for the prescription of very lowdose were low body weight (55.5% below 60 kg), anaemia (62.8%), chronic kidney disease (40.2%), active cancer (15.3%), concomitant anti-platelet use (26.7%), and prior major bleeding (19.7%). During a median follow-up duration of 8 (interquartile range 3–16) months, overall thromboembolic and bleeding events occurred in 16 (2.3%) and 88 (13.1%) patients, respectively. Compared to the expected event rates on the established risk scoring systems, patients receiving very low-dose edoxaban demonstrated a 61% reduction in ischemic stroke, a 68% reduction of ischemic stroke/transient ischemic attack/systemic embolism, whereas a 49% increase in major bleeding. Conclusions The prescription of very low-dose edoxaban was increased over time, attributable to various clinical factors. The use of very low-dose edoxaban reduced the expected risk of thromboembolic events.

Purpose: This study aimed to examine the effects of gonadotropin-releasing hormone agonist (GnRHa) treatment on final height outcomes in girls with idiopathic central precocious puberty (CPP) from the start of treatment to their postmenarche visit. Methods: We conducted a retrospective analysis of 200 girls with idiopathic CPP who received GnRHa therapy, focusing on auxological and clinical outcomes at treatment initiation, treatment completion, and the last, postmenarche visit. Results: The mean chronological age (CA) at GnRHa treatment initiation was 8.24±0.73 years. The mean duration of GnRHa treatment was 3.12±0.81 years. The average age at menarche was 12.73±0.56 years, occurring a mean of 17.15±5.52 months after completing GnRHa therapy. The predicted adult height (PAH) standard deviation score (SDS) after menarche (0.48±0.99) was significantly greater than before treatment (-1.33±1.46) (P<0.001). Factors including greater bone age advancement (P<0.001), lower height SDS for CA at treatment initiation (P<0.001), and higher midparental height SDS (P=0.001) were positively associated with an increase in PAH SDS at the last visit. However, near-final height and the increase in PAH SDS at the last visit were not significantly different between patients who received early treatment (<8 years) and those who received later treatment (8–9 years). Conclusion GnRHa treatment improved the final height outcomes in all girls with CPP, including those treated between 8 and 9 years of age.

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: Evidence remains limited on the real-world prescription of very low-dose oral anticoagulation among frail patients with atrial fibrillation (AF). We described the practice patterns, effectiveness, and safety of very low-dose edoxaban (15 mg once daily). Methods: Patients with AF prescribed edoxaban 15 mg once daily in 2 tertiary hospitals between 2016 and September 2022 were included. Baseline clinical characteristics and clinical outcomes of interest were thromboembolic and bleeding events. Results: A total of 674 patients were included (mean age 78.3±9.1, 49.7% aged ≥80 years, 49.3% women, median follow-up 1.0±1.2 years). Mean CHA 2 DS 2 -VASc score was 3.9±1.6, and the modified HAS-BLED score was 2.0±1.1. Between 2016 and 2022, the number of very lowdose edoxaban prescriptions increased. The main reasons for the prescription of very lowdose were low body weight (55.5% below 60 kg), anaemia (62.8%), chronic kidney disease (40.2%), active cancer (15.3%), concomitant anti-platelet use (26.7%), and prior major bleeding (19.7%). During a median follow-up duration of 8 (interquartile range 3–16) months, overall thromboembolic and bleeding events occurred in 16 (2.3%) and 88 (13.1%) patients, respectively. Compared to the expected event rates on the established risk scoring systems, patients receiving very low-dose edoxaban demonstrated a 61% reduction in ischemic stroke, a 68% reduction of ischemic stroke/transient ischemic attack/systemic embolism, whereas a 49% increase in major bleeding. Conclusions The prescription of very low-dose edoxaban was increased over time, attributable to various clinical factors. The use of very low-dose edoxaban reduced the expected risk of thromboembolic events.

Objective: Although high-density lipoprotein cholesterol (HDL-C) is inversely associated with hematologic malignancies, modification by smoking has not been reported. We investigated how smoking and menopausal status modify these association. Methods: This population-based cohort study enrolled cancer-free individuals who underwent a national cancer screening in 2010 and followed up until December 2017. HDL-C levels were classified into eight groups based on 10 mg/dL intervals: (<30, 30–39, 40–49, 50–59, 60–69, 70–79, 80–89, or ≥90 mg/dL). Results: Among 4,517,892 participants, 5887 had lymphoma, 3348 had leukemia, and 12151 had unspecified hematologic malignancies. The adjusted hazard ratios (aHRs) for the lowest HDL-C levels compared to the 70–79 mg/dL range were 1.83 (1.45–2.31) for lymphoma, 3.14 (2.41–4.08) for leukemia, and 2.34 (2.01–2.72) for unspecified hematologic malignancy.The effects of low HDL-C levels on hematologic malignancies were similar in both men and women. Low HDL-C levels were associated with a higher risk of leukemia regardless of smoking status, but extremely high HDL-C levels were linked to a higher risk of leukemia (aHR, 2.32; 95% confidence interval [95% CI], 1.18–4.55) only in current smokers.The hazardous effect of low HDL-C levels on lymphoma was significant only in never smokers (aHR, 2.01; 95% CI, 1.51–2.68). Hazardous effects of low HDL-C levels on leukemia were observed only in post-menopausal women (aHR, 2.94; 95% CI, 1.69–5.11). Conclusion Low HDL-C levels were associated with a higher risk of leukemia and lymphoma, with discrepancies based on smoking and menopausal status.

Purpose: This study aimed to examine the effects of gonadotropin-releasing hormone agonist (GnRHa) treatment on final height outcomes in girls with idiopathic central precocious puberty (CPP) from the start of treatment to their postmenarche visit. Methods: We conducted a retrospective analysis of 200 girls with idiopathic CPP who received GnRHa therapy, focusing on auxological and clinical outcomes at treatment initiation, treatment completion, and the last, postmenarche visit. Results: The mean chronological age (CA) at GnRHa treatment initiation was 8.24±0.73 years. The mean duration of GnRHa treatment was 3.12±0.81 years. The average age at menarche was 12.73±0.56 years, occurring a mean of 17.15±5.52 months after completing GnRHa therapy. The predicted adult height (PAH) standard deviation score (SDS) after menarche (0.48±0.99) was significantly greater than before treatment (-1.33±1.46) (P<0.001). Factors including greater bone age advancement (P<0.001), lower height SDS for CA at treatment initiation (P<0.001), and higher midparental height SDS (P=0.001) were positively associated with an increase in PAH SDS at the last visit. However, near-final height and the increase in PAH SDS at the last visit were not significantly different between patients who received early treatment (<8 years) and those who received later treatment (8–9 years). Conclusion GnRHa treatment improved the final height outcomes in all girls with CPP, including those treated between 8 and 9 years of age.