Objective： To examine the efficacy and safety of dual blockade of the renin-angiotensin-aldosterone system （RAAS） among patients with type 2 diabetic kidney disease. Data Sources： We searched the major literature ...Objective： To examine the efficacy and safety of dual blockade of the renin-angiotensin-aldosterone system （RAAS） among patients with type 2 diabetic kidney disease. Data Sources： We searched the major literature repositories, including the Cochrane Central Register of Controlled Trials, MEDLINE and EMBASE, for randomized clinical trials published between January 1990 and October 2015 that compared the efficacy and safety of the use of dual blockade of the RAAS versus the use ofmonothempy, without applying any language restrictions. Keywords for the searches included ＂＇diabetic nephropathy,＂ ＂chronic kidney disease,＂ ＂chronic renal insufficiency,＂ ＂diabetes mellitus,＂ ＂dual therapy,＂ ＂combined therapy,＂ ＂dual blockade,＂ ＂renin-angiotensin system,＂ ＂angiotensin-converting enzyme inhibitor,＂ ＂angiotensin-receptor blocker,＂ ＂aldosterone blockade,＂ ＂selective aldosterone blockade,＂ ＂renin inhibitor,＂ ＂direct renin inhibitor,＂ ＂mineralocorticoid receptor blocker,＂ etc. Study Selection： The selected articles were carefully reviewed. We excluded randomized clinical trials in which the kidney damage of patients was related to diseases other than diabetes mellitus. Results： Combination treatment with an angiotensin-converting enzyme inhibitor supplemented by an angiotensin I I receptor blocking agent is expected to provide a more complete blockade of the RAAS and a better control of hypertension. However, existing literature has presented mixed results, in particular, related to patient safety. In view of this, we conducted a comprehensive literature review in order to explain the rationale for dual blockade of the RAAS, and to discuss the pros and cons. Conclusions： Despite the negative results of some recent large-scale studies, it may be immature to declare that the dual blockade is a failure because of the complex nature of the RAAS surrounding its diversified functions and utility. Further trials are warranted to study the combination therapy as an evidence-based practice.展开更多
Objective: Despite cardiotoxicity overlap, the trastuzumab/pertuzumab and anthracycline combination remains crucial due to significant benefits. Pegylated liposomal doxorubicin(PLD), a less cardiotoxic anthracycline, ...Objective: Despite cardiotoxicity overlap, the trastuzumab/pertuzumab and anthracycline combination remains crucial due to significant benefits. Pegylated liposomal doxorubicin(PLD), a less cardiotoxic anthracycline, was evaluated for efficacy and cardiac safety when combined with cyclophosphamide and followed by taxanes with trastuzumab/pertuzumab in human epidermal growth factor receptor-2(HER2)-positive early breast cancer(BC).Methods: In this multicenter, phase II study, patients with confirmed HER2-positive early BC received four cycles of PLD(30-35 mg/m^(2)) and cyclophosphamide(600 mg/m^(2)), followed by four cycles of taxanes(docetaxel,90-100 mg/m^(2) or nab-paclitaxel, 260 mg/m^(2)), concomitant with eight cycles of trastuzumab(8 mg/kg loading dose,then 6 mg/kg) and pertuzumab(840 mg loading dose, then 420 mg) every 3 weeks. The primary endpoint was total pathological complete response(tp CR, yp T0/is yp N0). Secondary endpoints included breast p CR(bp CR),objective response rate(ORR), disease control rate, rate of breast-conserving surgery(BCS), and safety(with a focus on cardiotoxicity).Results: Between May 27, 2020 and May 11, 2022, 78 patients were treated with surgery, 42(53.8%) of whom had BCS. After neoadjuvant therapy, 47 [60.3%, 95% confidence interval(95% CI), 48.5%-71.2%] patients achieved tp CR, and 49(62.8%) achieved bp CR. ORRs were 76.9%(95% CI, 66.0%-85.7%) and 93.6%(95% CI,85.7%-97.9%) after 4-cycle and 8-cycle neoadjuvant therapy, respectively. Nine(11.5%) patients experienced asymptomatic left ventricular ejection fraction(LVEF) reductions of ≥10% from baseline, all with a minimum value of >55%. No treatment-related abnormal cardiac function changes were observed in mean N-terminal pro-BNP(NT-pro BNP), troponin I, or high-sensitivity troponin.Conclusions: This dual HER2-blockade with sequential polychemotherapy showed promising activity with rapid tumor regression in HER2-positive BC. Importantly, this regimen showed an acceptable safety profile,especially a low risk of cardiac events, suggesting it as an attractive treatment approach with a favorable risk-benefit balance.展开更多
Chronic kidney disease （CKD） is a significant interactive disease in patients with diabetes,hypertension, and cardiovascular disease with major morbidity and mortality consequences and high costs to the healthcare s...Chronic kidney disease （CKD） is a significant interactive disease in patients with diabetes,hypertension, and cardiovascular disease with major morbidity and mortality consequences and high costs to the healthcare system. CKD is characterized by a gradual loss of renal function. In most parts of the world, once end-stage renal disease （ESRD） occurs, patients who do not have access to maintenance dialysis or kidney transplantation would simply die. The data reported in the registry of the Chinese Society of Nephrology indicate that 41 000 ESRD patients were receiving dialysis in 1999, accounting for only 5% of the total population requiring renal replacement therapy.2 Delaying the progression of CKD to ESRD is an essential management goal for the clinical practice, particularly in developing countries.展开更多
文摘Objective： To examine the efficacy and safety of dual blockade of the renin-angiotensin-aldosterone system （RAAS） among patients with type 2 diabetic kidney disease. Data Sources： We searched the major literature repositories, including the Cochrane Central Register of Controlled Trials, MEDLINE and EMBASE, for randomized clinical trials published between January 1990 and October 2015 that compared the efficacy and safety of the use of dual blockade of the RAAS versus the use ofmonothempy, without applying any language restrictions. Keywords for the searches included ＂＇diabetic nephropathy,＂ ＂chronic kidney disease,＂ ＂chronic renal insufficiency,＂ ＂diabetes mellitus,＂ ＂dual therapy,＂ ＂combined therapy,＂ ＂dual blockade,＂ ＂renin-angiotensin system,＂ ＂angiotensin-converting enzyme inhibitor,＂ ＂angiotensin-receptor blocker,＂ ＂aldosterone blockade,＂ ＂selective aldosterone blockade,＂ ＂renin inhibitor,＂ ＂direct renin inhibitor,＂ ＂mineralocorticoid receptor blocker,＂ etc. Study Selection： The selected articles were carefully reviewed. We excluded randomized clinical trials in which the kidney damage of patients was related to diseases other than diabetes mellitus. Results： Combination treatment with an angiotensin-converting enzyme inhibitor supplemented by an angiotensin I I receptor blocking agent is expected to provide a more complete blockade of the RAAS and a better control of hypertension. However, existing literature has presented mixed results, in particular, related to patient safety. In view of this, we conducted a comprehensive literature review in order to explain the rationale for dual blockade of the RAAS, and to discuss the pros and cons. Conclusions： Despite the negative results of some recent large-scale studies, it may be immature to declare that the dual blockade is a failure because of the complex nature of the RAAS surrounding its diversified functions and utility. Further trials are warranted to study the combination therapy as an evidence-based practice.
基金supported by the National Natural Science Foundation of China (No. 82003311, No. 82061148016, No. 82230057 and No. 82272859)National Key R&D Program of China (No. 2022YFC2505101)+2 种基金Sun Yat-Sen Clinical Research Cultivating Program (No. SYS-Q202004)Beijing Medical Award Foundation (No. YXJL2020-0941-0760)Guangzhou Science and Technology Program (No. 202102010272 and No. 202201020486)。
文摘Objective: Despite cardiotoxicity overlap, the trastuzumab/pertuzumab and anthracycline combination remains crucial due to significant benefits. Pegylated liposomal doxorubicin(PLD), a less cardiotoxic anthracycline, was evaluated for efficacy and cardiac safety when combined with cyclophosphamide and followed by taxanes with trastuzumab/pertuzumab in human epidermal growth factor receptor-2(HER2)-positive early breast cancer(BC).Methods: In this multicenter, phase II study, patients with confirmed HER2-positive early BC received four cycles of PLD(30-35 mg/m^(2)) and cyclophosphamide(600 mg/m^(2)), followed by four cycles of taxanes(docetaxel,90-100 mg/m^(2) or nab-paclitaxel, 260 mg/m^(2)), concomitant with eight cycles of trastuzumab(8 mg/kg loading dose,then 6 mg/kg) and pertuzumab(840 mg loading dose, then 420 mg) every 3 weeks. The primary endpoint was total pathological complete response(tp CR, yp T0/is yp N0). Secondary endpoints included breast p CR(bp CR),objective response rate(ORR), disease control rate, rate of breast-conserving surgery(BCS), and safety(with a focus on cardiotoxicity).Results: Between May 27, 2020 and May 11, 2022, 78 patients were treated with surgery, 42(53.8%) of whom had BCS. After neoadjuvant therapy, 47 [60.3%, 95% confidence interval(95% CI), 48.5%-71.2%] patients achieved tp CR, and 49(62.8%) achieved bp CR. ORRs were 76.9%(95% CI, 66.0%-85.7%) and 93.6%(95% CI,85.7%-97.9%) after 4-cycle and 8-cycle neoadjuvant therapy, respectively. Nine(11.5%) patients experienced asymptomatic left ventricular ejection fraction(LVEF) reductions of ≥10% from baseline, all with a minimum value of >55%. No treatment-related abnormal cardiac function changes were observed in mean N-terminal pro-BNP(NT-pro BNP), troponin I, or high-sensitivity troponin.Conclusions: This dual HER2-blockade with sequential polychemotherapy showed promising activity with rapid tumor regression in HER2-positive BC. Importantly, this regimen showed an acceptable safety profile,especially a low risk of cardiac events, suggesting it as an attractive treatment approach with a favorable risk-benefit balance.
基金the National Nature Science Foundation (No. 30330300)
文摘Chronic kidney disease （CKD） is a significant interactive disease in patients with diabetes,hypertension, and cardiovascular disease with major morbidity and mortality consequences and high costs to the healthcare system. CKD is characterized by a gradual loss of renal function. In most parts of the world, once end-stage renal disease （ESRD） occurs, patients who do not have access to maintenance dialysis or kidney transplantation would simply die. The data reported in the registry of the Chinese Society of Nephrology indicate that 41 000 ESRD patients were receiving dialysis in 1999, accounting for only 5% of the total population requiring renal replacement therapy.2 Delaying the progression of CKD to ESRD is an essential management goal for the clinical practice, particularly in developing countries.
