Background and Objectives: Outcomes of deferring percutaneous coronary intervention (PCI) without invasive physiologic assessment for intermediate coronary lesions is uncertain.We sought to compare long-term outcomes between medical treatment and PCI of intermediate lesions without invasive physiologic assessment. Methods: A total of 899 patients with intermediate coronary lesions between 50% and 70% diameter-stenosis were randomized to the conservative group (n=449) or the aggressive group (n=450). For intermediate lesions, PCI was performed in the aggressive group, but was deferred in the conservative group. The primary endpoint was major adverse cardiac events (MACE, a composite of all-cause death, myocardial infarction [MI], or ischemia-driven any revascularization) at 3 years. Results: The number of treated lesions per patient was 0.8±0.9 in the conservative group and 1.7±0.9 in the aggressive group (p=0.001). At 3 years, the conservative group had a significantly higher incidence of MACE than the aggressive group (13.8% vs. 9.3%; hazard ratio [HR], 1.49; 95% confidence interval [CI], 1.00–2.21; p=0.049), mainly driven by revascularization of target intermediate lesion (6.5% vs. 1.1%; HR, 5.69; 95% CI, 2.20–14.73;p<0.001). Between 1 and 3 years after the index procedure, compared to the aggressive group, the conservative group had significantly higher incidence of cardiac death or MI (3.2% vs.0.7%; HR, 4.34; 95% CI, 1.24–15.22; p=0.022) and ischemia-driven any revascularization. Conclusions For intermediate lesions, medical therapy alone, guided only by angiography, was associated with a higher risk of MACE at 3 years compared with performing PCI, mainly due to increased revascularization.

Background and Objectives: Outcomes of deferring percutaneous coronary intervention (PCI) without invasive physiologic assessment for intermediate coronary lesions is uncertain.We sought to compare long-term outcomes between medical treatment and PCI of intermediate lesions without invasive physiologic assessment. Methods: A total of 899 patients with intermediate coronary lesions between 50% and 70% diameter-stenosis were randomized to the conservative group (n=449) or the aggressive group (n=450). For intermediate lesions, PCI was performed in the aggressive group, but was deferred in the conservative group. The primary endpoint was major adverse cardiac events (MACE, a composite of all-cause death, myocardial infarction [MI], or ischemia-driven any revascularization) at 3 years. Results: The number of treated lesions per patient was 0.8±0.9 in the conservative group and 1.7±0.9 in the aggressive group (p=0.001). At 3 years, the conservative group had a significantly higher incidence of MACE than the aggressive group (13.8% vs. 9.3%; hazard ratio [HR], 1.49; 95% confidence interval [CI], 1.00–2.21; p=0.049), mainly driven by revascularization of target intermediate lesion (6.5% vs. 1.1%; HR, 5.69; 95% CI, 2.20–14.73;p<0.001). Between 1 and 3 years after the index procedure, compared to the aggressive group, the conservative group had significantly higher incidence of cardiac death or MI (3.2% vs.0.7%; HR, 4.34; 95% CI, 1.24–15.22; p=0.022) and ischemia-driven any revascularization. Conclusions For intermediate lesions, medical therapy alone, guided only by angiography, was associated with a higher risk of MACE at 3 years compared with performing PCI, mainly due to increased revascularization.

Background and Objectives: Outcomes of deferring percutaneous coronary intervention (PCI) without invasive physiologic assessment for intermediate coronary lesions is uncertain.We sought to compare long-term outcomes between medical treatment and PCI of intermediate lesions without invasive physiologic assessment. Methods: A total of 899 patients with intermediate coronary lesions between 50% and 70% diameter-stenosis were randomized to the conservative group (n=449) or the aggressive group (n=450). For intermediate lesions, PCI was performed in the aggressive group, but was deferred in the conservative group. The primary endpoint was major adverse cardiac events (MACE, a composite of all-cause death, myocardial infarction [MI], or ischemia-driven any revascularization) at 3 years. Results: The number of treated lesions per patient was 0.8±0.9 in the conservative group and 1.7±0.9 in the aggressive group (p=0.001). At 3 years, the conservative group had a significantly higher incidence of MACE than the aggressive group (13.8% vs. 9.3%; hazard ratio [HR], 1.49; 95% confidence interval [CI], 1.00–2.21; p=0.049), mainly driven by revascularization of target intermediate lesion (6.5% vs. 1.1%; HR, 5.69; 95% CI, 2.20–14.73;p<0.001). Between 1 and 3 years after the index procedure, compared to the aggressive group, the conservative group had significantly higher incidence of cardiac death or MI (3.2% vs.0.7%; HR, 4.34; 95% CI, 1.24–15.22; p=0.022) and ischemia-driven any revascularization. Conclusions For intermediate lesions, medical therapy alone, guided only by angiography, was associated with a higher risk of MACE at 3 years compared with performing PCI, mainly due to increased revascularization.

Background and Objectives: Outcomes of deferring percutaneous coronary intervention (PCI) without invasive physiologic assessment for intermediate coronary lesions is uncertain.We sought to compare long-term outcomes between medical treatment and PCI of intermediate lesions without invasive physiologic assessment. Methods: A total of 899 patients with intermediate coronary lesions between 50% and 70% diameter-stenosis were randomized to the conservative group (n=449) or the aggressive group (n=450). For intermediate lesions, PCI was performed in the aggressive group, but was deferred in the conservative group. The primary endpoint was major adverse cardiac events (MACE, a composite of all-cause death, myocardial infarction [MI], or ischemia-driven any revascularization) at 3 years. Results: The number of treated lesions per patient was 0.8±0.9 in the conservative group and 1.7±0.9 in the aggressive group (p=0.001). At 3 years, the conservative group had a significantly higher incidence of MACE than the aggressive group (13.8% vs. 9.3%; hazard ratio [HR], 1.49; 95% confidence interval [CI], 1.00–2.21; p=0.049), mainly driven by revascularization of target intermediate lesion (6.5% vs. 1.1%; HR, 5.69; 95% CI, 2.20–14.73;p<0.001). Between 1 and 3 years after the index procedure, compared to the aggressive group, the conservative group had significantly higher incidence of cardiac death or MI (3.2% vs.0.7%; HR, 4.34; 95% CI, 1.24–15.22; p=0.022) and ischemia-driven any revascularization. Conclusions For intermediate lesions, medical therapy alone, guided only by angiography, was associated with a higher risk of MACE at 3 years compared with performing PCI, mainly due to increased revascularization.

We investigated whether endurance exercise training (EXT) ameliorates circadian rhythm (CR)-induced risk factors by improving skeletal muscle (SKM) mitochondrial biogenesis, reducing oxidative stress, and modulating apoptotic protein expression. We distinguished between regular and shift workers using the National Health and Nutrition Examination Survey (NHANES) and investigated the health problems caused by shift work (CR disturbance) and the potential therapeutic effects of exercise. In our animal study, 36 rats underwent 12 weeks of CR disturbance, divided into regular and irregular CR groups. These groups were further split into EXT (n = 12) and sedentary (n = 12) for an additional 8 weeks. We analyzed SKM tissue to understand the molecular changes induced by CR and EXT. NHANES data were analyzed using SAS 9.4 and Prism 8 software, while experimental animal data were analyzed using Prism 8 software. The statistical procedures used in each experiment are indicated in the figure legends. Our studies showed that CR disturbance increases dyslipidemia, alters circadian clock proteins (BMAL1, PER2), raises apoptotic protein levels, and reduces mitochondrial biogenesis in SKM. EXT improved LDL-C and HDLC levels without affecting muscle BMAL1 expression. It also enhanced mitochondrial biogenesis (AMPK, PGC-1α, Tfam, NADH-UO, COX-I), antioxidant levels (Catalase, SOD1, SOD2), and apoptotic protein (p53, Bax/Bcl2) expression or activity in SKM. We demonstrated that shift work-induced CR disturbance leads to dyslipidemia, diminished mitochondrial biogenesis, and reduced antioxidant capacity in SKM. However, EXT can counteract dyslipidemia under CR disturbance, potentially lowering the risk of cardiovascular disorders.

We investigated whether endurance exercise training (EXT) ameliorates circadian rhythm (CR)-induced risk factors by improving skeletal muscle (SKM) mitochondrial biogenesis, reducing oxidative stress, and modulating apoptotic protein expression. We distinguished between regular and shift workers using the National Health and Nutrition Examination Survey (NHANES) and investigated the health problems caused by shift work (CR disturbance) and the potential therapeutic effects of exercise. In our animal study, 36 rats underwent 12 weeks of CR disturbance, divided into regular and irregular CR groups. These groups were further split into EXT (n = 12) and sedentary (n = 12) for an additional 8 weeks. We analyzed SKM tissue to understand the molecular changes induced by CR and EXT. NHANES data were analyzed using SAS 9.4 and Prism 8 software, while experimental animal data were analyzed using Prism 8 software. The statistical procedures used in each experiment are indicated in the figure legends. Our studies showed that CR disturbance increases dyslipidemia, alters circadian clock proteins (BMAL1, PER2), raises apoptotic protein levels, and reduces mitochondrial biogenesis in SKM. EXT improved LDL-C and HDLC levels without affecting muscle BMAL1 expression. It also enhanced mitochondrial biogenesis (AMPK, PGC-1α, Tfam, NADH-UO, COX-I), antioxidant levels (Catalase, SOD1, SOD2), and apoptotic protein (p53, Bax/Bcl2) expression or activity in SKM. We demonstrated that shift work-induced CR disturbance leads to dyslipidemia, diminished mitochondrial biogenesis, and reduced antioxidant capacity in SKM. However, EXT can counteract dyslipidemia under CR disturbance, potentially lowering the risk of cardiovascular disorders.

We investigated whether endurance exercise training (EXT) ameliorates circadian rhythm (CR)-induced risk factors by improving skeletal muscle (SKM) mitochondrial biogenesis, reducing oxidative stress, and modulating apoptotic protein expression. We distinguished between regular and shift workers using the National Health and Nutrition Examination Survey (NHANES) and investigated the health problems caused by shift work (CR disturbance) and the potential therapeutic effects of exercise. In our animal study, 36 rats underwent 12 weeks of CR disturbance, divided into regular and irregular CR groups. These groups were further split into EXT (n = 12) and sedentary (n = 12) for an additional 8 weeks. We analyzed SKM tissue to understand the molecular changes induced by CR and EXT. NHANES data were analyzed using SAS 9.4 and Prism 8 software, while experimental animal data were analyzed using Prism 8 software. The statistical procedures used in each experiment are indicated in the figure legends. Our studies showed that CR disturbance increases dyslipidemia, alters circadian clock proteins (BMAL1, PER2), raises apoptotic protein levels, and reduces mitochondrial biogenesis in SKM. EXT improved LDL-C and HDLC levels without affecting muscle BMAL1 expression. It also enhanced mitochondrial biogenesis (AMPK, PGC-1α, Tfam, NADH-UO, COX-I), antioxidant levels (Catalase, SOD1, SOD2), and apoptotic protein (p53, Bax/Bcl2) expression or activity in SKM. We demonstrated that shift work-induced CR disturbance leads to dyslipidemia, diminished mitochondrial biogenesis, and reduced antioxidant capacity in SKM. However, EXT can counteract dyslipidemia under CR disturbance, potentially lowering the risk of cardiovascular disorders.

Purpose: For the treatment of locally advanced rectal cancer (LARC), research on primary lesions with mesorectal fascia (MRF) involvement is lacking. This study analyzed the clinical outcomes and efficacy of dose-escalated neoadjuvant concurrent chemoradiotherapy (NCRT) to patients with LARC involving MRF. Materials and Methods: We retrospectively reviewed 301 patients who were diagnosed with LARC involving MRF and underwent NCRT followed by total mesorectal excision (TME). Patients who received radiotherapy (RT) doses of ≤50.4 Gy were defined as the non-boost group, while ≥54.0 Gy as the boost group. Pathological tumor response and survival outcomes, including intrapelvic recurrence-free survival (IPRFS), distant metastases-free survival (DMFS) and overall survival (OS), were analyzed. Results: A total of 269 patients (89.4%) achieved a negative pathological circumferential resection margin and 104 (34.6%) had good pathological tumor regression grades. With a median follow-up of 32.4 months, IPRFS, DMFS, and OS rates at 5-years were 88.6%, 78.0%, and 91.2%, respectively. In the subgroup analysis by RT dose, the boost group included more advanced clinical stages of patients. For the non-boost group and boost group, 5-year IPRFS rates were 90.3% and 87.0% (p = 0.242), 5-year DMFS rates were 82.0% and 71.3% (p = 0.105), and 5-year OS rates were 93.0% and 80.6% (p = 0.439), respectively. Treatment related toxicity was comparable between the two groups (p = 0.211). Conclusion Although this retrospective study failed to confirm the efficacy of dose-escalated NCRT, favorable IPRFS and pathological complete response was achieved with NCRT followed by TME. Further studies combining patient customized RT dose with systemic therapies are needed.

We investigated whether endurance exercise training (EXT) ameliorates circadian rhythm (CR)-induced risk factors by improving skeletal muscle (SKM) mitochondrial biogenesis, reducing oxidative stress, and modulating apoptotic protein expression. We distinguished between regular and shift workers using the National Health and Nutrition Examination Survey (NHANES) and investigated the health problems caused by shift work (CR disturbance) and the potential therapeutic effects of exercise. In our animal study, 36 rats underwent 12 weeks of CR disturbance, divided into regular and irregular CR groups. These groups were further split into EXT (n = 12) and sedentary (n = 12) for an additional 8 weeks. We analyzed SKM tissue to understand the molecular changes induced by CR and EXT. NHANES data were analyzed using SAS 9.4 and Prism 8 software, while experimental animal data were analyzed using Prism 8 software. The statistical procedures used in each experiment are indicated in the figure legends. Our studies showed that CR disturbance increases dyslipidemia, alters circadian clock proteins (BMAL1, PER2), raises apoptotic protein levels, and reduces mitochondrial biogenesis in SKM. EXT improved LDL-C and HDLC levels without affecting muscle BMAL1 expression. It also enhanced mitochondrial biogenesis (AMPK, PGC-1α, Tfam, NADH-UO, COX-I), antioxidant levels (Catalase, SOD1, SOD2), and apoptotic protein (p53, Bax/Bcl2) expression or activity in SKM. We demonstrated that shift work-induced CR disturbance leads to dyslipidemia, diminished mitochondrial biogenesis, and reduced antioxidant capacity in SKM. However, EXT can counteract dyslipidemia under CR disturbance, potentially lowering the risk of cardiovascular disorders.

We investigated whether endurance exercise training (EXT) ameliorates circadian rhythm (CR)-induced risk factors by improving skeletal muscle (SKM) mitochondrial biogenesis, reducing oxidative stress, and modulating apoptotic protein expression. We distinguished between regular and shift workers using the National Health and Nutrition Examination Survey (NHANES) and investigated the health problems caused by shift work (CR disturbance) and the potential therapeutic effects of exercise. In our animal study, 36 rats underwent 12 weeks of CR disturbance, divided into regular and irregular CR groups. These groups were further split into EXT (n = 12) and sedentary (n = 12) for an additional 8 weeks. We analyzed SKM tissue to understand the molecular changes induced by CR and EXT. NHANES data were analyzed using SAS 9.4 and Prism 8 software, while experimental animal data were analyzed using Prism 8 software. The statistical procedures used in each experiment are indicated in the figure legends. Our studies showed that CR disturbance increases dyslipidemia, alters circadian clock proteins (BMAL1, PER2), raises apoptotic protein levels, and reduces mitochondrial biogenesis in SKM. EXT improved LDL-C and HDLC levels without affecting muscle BMAL1 expression. It also enhanced mitochondrial biogenesis (AMPK, PGC-1α, Tfam, NADH-UO, COX-I), antioxidant levels (Catalase, SOD1, SOD2), and apoptotic protein (p53, Bax/Bcl2) expression or activity in SKM. We demonstrated that shift work-induced CR disturbance leads to dyslipidemia, diminished mitochondrial biogenesis, and reduced antioxidant capacity in SKM. However, EXT can counteract dyslipidemia under CR disturbance, potentially lowering the risk of cardiovascular disorders.