Purpose: Adjuvant pembrolizumab improved disease-free survival (DFS) and overall survival (OS) versus placebo in participants with renal cell carcinoma (RCC) at increased risk of recurrence after nephrectomy in the global phase 3 KEYNOTE-564 study. This post hoc subgroup analysis evaluated the efficacy and safety of adjuvant pembrolizumab in East Asian (Japan, South Korea, and Taiwan) participants enrolled in KEYNOTE-564. Materials and Methods: Eligible participants were randomly assigned 1:1 to receive adjuvant pembrolizumab 200 mg or placebo intravenously every 3 weeks for ≤ 17 cycles. The primary endpoint was DFS by investigator assessment. OS was a key secondary endpoint. Safety was a secondary endpoint. Results: The East Asian subgroup included 126 participants (pembrolizumab, n=58; placebo, n=68). Median follow-up was 62.1 months (range, 49.6 to 73.0 months). Hazard ratio for DFS with pembrolizumab versus placebo was 0.70 (95% confidence interval 0.41 to 1.20). Median DFS was not reached with pembrolizumab versus 58.8 months with placebo; estimated 48-month rate was 61.3% versus 51.2%. Hazard ratio for OS was 0.47 (95% confidence interval, 0.15 to 1.49). Median OS was not reached with pembrolizumab and placebo; estimated 48-month rate was 94.8% versus 91.2%. Treatment-related adverse events occurred in 70.7% of participants (29.3% grade 3 or 4) receiving pembrolizumab and 36.8% of participants (0.0% grade 3 or 4) receiving placebo. No pembrolizumab-related deaths occurred. Conclusion In the KEYNOTE-564 East Asian subgroup, adjuvant pembrolizumab provided DFS and OS benefits versus placebo and had a safety profile consistent with the global results. These results further support pembrolizumab as adjuvant treatment for East Asian patients with RCC at increased risk of recurrence after nephrectomy.

Objectives: . Idiopathic sudden sensorineural hearing loss (ISSNHL) is a significant cause of hearing loss. Intratympanic steroid injection (ITSI) is commonly used as an initial or salvage treatment; however, the lack of a standardized treatment protocol has resulted in variability in clinical practice. In addition, no efficient prediction model currently exists to support personalized management. Therefore, this study aimed to develop tailored management strategies for ISSNHL using a machine-learning model. Methods: . This retrospective multicenter cohort study was conducted between January 2015 and December 2020, with data analysis performed between January 2021 and March 2024. Patients were selected based on the International Classification of Diseases, 10th Revision criteria for ISSNHL, along with relevant medication and procedure codes. Patients with pure-tone audiogram results not meeting ISSNHL criteria, better initial hearing in the affected ear, an identifiable etiology, no post-treatment audiogram, or delayed treatment (>6 weeks) were excluded. We included 770 patients diagnosed with ISSNHL who received ITSI. The primary outcome was the area under the receiver operating characteristic curve for prediction performance. Recovery status was determined using the last pure-tone audiogram. Modeling was conducted on the Quanta for Medical Care AI platform using five machine-learning algorithms and a nested cross-validation framework, in which feature selection and hyperparameter tuning were performed in the inner folds and model performance was evaluated in the outer folds. Results: . A random forest classifier outperformed the other models in predicting hearing outcomes, achieving an area under the receiver operating characteristic curve of 0.788. Time to ITSI was the most influential treatment-related factor, with ITSI administered within 10 days of hearing loss being associated with better outcomes. This model can be used to provide personalized prognostic estimates under different treatment protocols. Conclusion . The machine-learning-based prediction model facilitates personalized treatment strategies and timely treatment adjustments for ISSNHL, thereby optimizing the likelihood of complete recovery.

Background: Delivering a poor prognosis to patients and their families is critically challenging in pediatric populations. The application of palliative care (PC) provides a bridge between accepting the occurrence of mortality and offering lifelong support.However, little is known about the specifics of PC. This study aims to explore the unmet need for PC in pediatric populations. Methods: We retrospectively reviewed the medical records of mortality cases in the Department of Pediatric Hematology and Oncology at Chang Gung Memorial Hospital. Statistical tests, including Chi-square and Student’s t-tests, were applied to determine the differences between early and late intervention groups in terms of the timing of PC introduction. Results: During the study period, 41 patients were included. Their median age was 11.8 years (IQR, 7.6-15.9). The majority of the disease statuses were refractory or relapsing (R/R). The incidence of memento application was significantly higher in the early intervention group (47.6% vs. 10%, P=0.0081). Vital signs variations tended to be end-of-life (EoL) indicators in this study. Conclusion The early introduction of PC encourages families to accompany their beloved child. EoL signs in the pediatric population include vital sign variations. With the presence of relevant EoL signs, clinical physicians can apply PC earlier to meet the needs.

Background/Aims: Treatment indications for patients with chronic hepatitis B (CHB) remain contentious, particularly for patients with mild alanine aminotransferase (ALT) elevation. We aimed to evaluate treatment effects in this patient population. Methods: This rollover study extended a placebo-controlled trial that enrolled non-cirrhotic patients with CHB and ALT levels below two times the upper limit of normal. Following 3 years of randomized intervention with either tenofovir disoproxil fumarate (TDF) or placebo, participants were rolled over to open-label TDF for 3 years. Liver biopsies were performed before and after the treatment to evaluate histopathological changes. Virological, biochemical, and serological outcomes were also assessed (NCT02463019). Results: Of 146 enrolled patients (median age 47 years, 80.8% male), 123 completed the study with paired biopsies. Overall, the Ishak fibrosis score decreased in 74 (60.2%), remained unchanged in 32 (26.0%), and increased in 17 (13.8%) patients (p<0.0001). The Knodell necroinflammation score decreased in 58 (47.2%), remained unchanged in 29 (23.6%), and increased in 36 (29.3%) patients (p=0.0038). The proportion of patients with an Ishak score ≥ 3 significantly decreased from 26.8% (n=33) to 9.8% (n=12) (p=0.0002). Histological improvements were more pronounced in patients switching from placebo. Virological and biochemical outcomes also improved in placebo switchers and remained stable in patients who continued TDF. However, serum HBsAg levels did not change and no patient cleared HBsAg. Conclusions In CHB patients with minimally raised ALT, favorable histopathological, biochemical, and virological outcomes were observed following 3-year TDF treatment, for both treatment-naïve patients and those already on therapy.

Background: Delivering a poor prognosis to patients and their families is critically challenging in pediatric populations. The application of palliative care (PC) provides a bridge between accepting the occurrence of mortality and offering lifelong support.However, little is known about the specifics of PC. This study aims to explore the unmet need for PC in pediatric populations. Methods: We retrospectively reviewed the medical records of mortality cases in the Department of Pediatric Hematology and Oncology at Chang Gung Memorial Hospital. Statistical tests, including Chi-square and Student’s t-tests, were applied to determine the differences between early and late intervention groups in terms of the timing of PC introduction. Results: During the study period, 41 patients were included. Their median age was 11.8 years (IQR, 7.6-15.9). The majority of the disease statuses were refractory or relapsing (R/R). The incidence of memento application was significantly higher in the early intervention group (47.6% vs. 10%, P=0.0081). Vital signs variations tended to be end-of-life (EoL) indicators in this study. Conclusion The early introduction of PC encourages families to accompany their beloved child. EoL signs in the pediatric population include vital sign variations. With the presence of relevant EoL signs, clinical physicians can apply PC earlier to meet the needs.

Background: Delivering a poor prognosis to patients and their families is critically challenging in pediatric populations. The application of palliative care (PC) provides a bridge between accepting the occurrence of mortality and offering lifelong support.However, little is known about the specifics of PC. This study aims to explore the unmet need for PC in pediatric populations. Methods: We retrospectively reviewed the medical records of mortality cases in the Department of Pediatric Hematology and Oncology at Chang Gung Memorial Hospital. Statistical tests, including Chi-square and Student’s t-tests, were applied to determine the differences between early and late intervention groups in terms of the timing of PC introduction. Results: During the study period, 41 patients were included. Their median age was 11.8 years (IQR, 7.6-15.9). The majority of the disease statuses were refractory or relapsing (R/R). The incidence of memento application was significantly higher in the early intervention group (47.6% vs. 10%, P=0.0081). Vital signs variations tended to be end-of-life (EoL) indicators in this study. Conclusion The early introduction of PC encourages families to accompany their beloved child. EoL signs in the pediatric population include vital sign variations. With the presence of relevant EoL signs, clinical physicians can apply PC earlier to meet the needs.

Background/Aims: Treatment indications for patients with chronic hepatitis B (CHB) remain contentious, particularly for patients with mild alanine aminotransferase (ALT) elevation. We aimed to evaluate treatment effects in this patient population. Methods: This rollover study extended a placebo-controlled trial that enrolled non-cirrhotic patients with CHB and ALT levels below two times the upper limit of normal. Following 3 years of randomized intervention with either tenofovir disoproxil fumarate (TDF) or placebo, participants were rolled over to open-label TDF for 3 years. Liver biopsies were performed before and after the treatment to evaluate histopathological changes. Virological, biochemical, and serological outcomes were also assessed (NCT02463019). Results: Of 146 enrolled patients (median age 47 years, 80.8% male), 123 completed the study with paired biopsies. Overall, the Ishak fibrosis score decreased in 74 (60.2%), remained unchanged in 32 (26.0%), and increased in 17 (13.8%) patients (p<0.0001). The Knodell necroinflammation score decreased in 58 (47.2%), remained unchanged in 29 (23.6%), and increased in 36 (29.3%) patients (p=0.0038). The proportion of patients with an Ishak score ≥ 3 significantly decreased from 26.8% (n=33) to 9.8% (n=12) (p=0.0002). Histological improvements were more pronounced in patients switching from placebo. Virological and biochemical outcomes also improved in placebo switchers and remained stable in patients who continued TDF. However, serum HBsAg levels did not change and no patient cleared HBsAg. Conclusions In CHB patients with minimally raised ALT, favorable histopathological, biochemical, and virological outcomes were observed following 3-year TDF treatment, for both treatment-naïve patients and those already on therapy.

Background/Aims: Treatment indications for patients with chronic hepatitis B (CHB) remain contentious, particularly for patients with mild alanine aminotransferase (ALT) elevation. We aimed to evaluate treatment effects in this patient population. Methods: This rollover study extended a placebo-controlled trial that enrolled non-cirrhotic patients with CHB and ALT levels below two times the upper limit of normal. Following 3 years of randomized intervention with either tenofovir disoproxil fumarate (TDF) or placebo, participants were rolled over to open-label TDF for 3 years. Liver biopsies were performed before and after the treatment to evaluate histopathological changes. Virological, biochemical, and serological outcomes were also assessed (NCT02463019). Results: Of 146 enrolled patients (median age 47 years, 80.8% male), 123 completed the study with paired biopsies. Overall, the Ishak fibrosis score decreased in 74 (60.2%), remained unchanged in 32 (26.0%), and increased in 17 (13.8%) patients (p<0.0001). The Knodell necroinflammation score decreased in 58 (47.2%), remained unchanged in 29 (23.6%), and increased in 36 (29.3%) patients (p=0.0038). The proportion of patients with an Ishak score ≥ 3 significantly decreased from 26.8% (n=33) to 9.8% (n=12) (p=0.0002). Histological improvements were more pronounced in patients switching from placebo. Virological and biochemical outcomes also improved in placebo switchers and remained stable in patients who continued TDF. However, serum HBsAg levels did not change and no patient cleared HBsAg. Conclusions In CHB patients with minimally raised ALT, favorable histopathological, biochemical, and virological outcomes were observed following 3-year TDF treatment, for both treatment-naïve patients and those already on therapy.

Background: Delivering a poor prognosis to patients and their families is critically challenging in pediatric populations. The application of palliative care (PC) provides a bridge between accepting the occurrence of mortality and offering lifelong support.However, little is known about the specifics of PC. This study aims to explore the unmet need for PC in pediatric populations. Methods: We retrospectively reviewed the medical records of mortality cases in the Department of Pediatric Hematology and Oncology at Chang Gung Memorial Hospital. Statistical tests, including Chi-square and Student’s t-tests, were applied to determine the differences between early and late intervention groups in terms of the timing of PC introduction. Results: During the study period, 41 patients were included. Their median age was 11.8 years (IQR, 7.6-15.9). The majority of the disease statuses were refractory or relapsing (R/R). The incidence of memento application was significantly higher in the early intervention group (47.6% vs. 10%, P=0.0081). Vital signs variations tended to be end-of-life (EoL) indicators in this study. Conclusion The early introduction of PC encourages families to accompany their beloved child. EoL signs in the pediatric population include vital sign variations. With the presence of relevant EoL signs, clinical physicians can apply PC earlier to meet the needs.

Objectives: The effectiveness of combining romosozumab (ROMO) with denosumab (Dmab) remains uncertain.We compare the six-month effects of Dmab plus monthly ROMO versus Dmab plus daily teriparatide (TPTD) on bone mineral density (BMD) in treatment-naïve postmenopausal women with osteoporosis. Methods: This retrospective cohort study analyzed 26 treatment-naïve postmenopausal women with primary osteoporosis. Participants received either a monthly regimen of ROMO and Dmab (N = 14) or a daily regimen of TPTD plus Dmab (N = 12). BMD at the lumbar spine, total hip, and femoral neck was measured at baseline, 3 months, and 6 months by dual-energy X-ray absorptiometry. Serum levels of C-terminal telopeptide (CTX) and procollagen type I N-terminal propeptide (P1NP) were assessed at the same intervals. Results: Both regimens significantly improved lumbar spine BMD at 6 months (ROMO + Dmab: +9.75%; TPTD +Dmab: +7.42%). Improvements in total hip and femoral neck BMD were modest and similar between groups (~2%). Serum CTX and P1NP were significantly suppressed in both groups at 3 months, but P1NP suppression waned in the TPTD + Dmab group by 6 months. No statistically significant differences in BMD or marker changes were detected between the two regimens. Conclusions Both combination therapies effectively improve lumbar spine BMD over 6 months. The ROMO +Dmab regimen yielded numerically greater increases with fewer injections.