Following the characterization of a human betaretrovirus in patients with primary biliary cirrhosis(PBC),pilot studies using antiretroviral therapy have been conducted as proof of principal to establish a link of viru...Following the characterization of a human betaretrovirus in patients with primary biliary cirrhosis(PBC),pilot studies using antiretroviral therapy have been conducted as proof of principal to establish a link of virus with disease and with the eventual aim to find better adjunct therapies for patients unresponsive to ursodeoxycholic acid.In the first open label pilot study,the reverse transcriptase inhibitor lamivudine had little demonstrable biochemical or histological effect after 1 year.Whereas,lamivudine in combination with zidovudine was associated with a significant reduction in alkaline phosphatase as well as improvement in necroinflammatory score,cholangitis and ductopenia over a 12 mo period.A double blind,multi-center randomized controlled trial using lamivudine with zidovudine for 6 mo confirmed a significant reduction in alkaline phosphatase,ALT and AST in patients on antiviral therapy.However,none of the patients achieved the stringent endpoint criteria for normalization of alkaline phosphatase.Furthermore,some patients developed biochemical rebound consistent with drug resistance.A major fault of these studies has been the inability to measure the viral load in peripheral blood and therefore,provide a direct correlation between improvement of hepatic biochemistry and reduction in viral load.Nevertheless,viral mutants to lamivudine with zidovudine were later characterized in the NOD.c3c4 mouse model of PBC that has been used to test other antiretroviral regimens to betaretrovirus.The combination of tenofovir and emtricitabine reverse transcriptase inhibitors and the HIV protease inhibitor,lopinavir were found to abrogate cholangitis in the NOD.c3c4 mouse model and the same regimen normalized the liver tests in a PBC patient with HIV and human betaretrovirus infection.This combination antiretroviral therapy has now been used in a double blind randomized controlled crossover study for patients with PBC followed by an open label extension study.Only a third of the PBC patients were able to tolerate the lopinavir but those maintained on tenofovir,emtricitabine and lopinavir experienced sustained and clinically meaningful reduction in hepatic biochemistry.While we await the histological and virological evaluation,it is clear that better tolerated regimens of antiretroviral treatment will be required in future clinical trials.展开更多
BACKGROUND Targeted therapy(TT)has resulted in controversial efficacy as first-line treatment for biliary tract cancer(BTC).More efficacy comparisons are required to clarify the overall effects of chemotherapy(CT)comb...BACKGROUND Targeted therapy(TT)has resulted in controversial efficacy as first-line treatment for biliary tract cancer(BTC).More efficacy comparisons are required to clarify the overall effects of chemotherapy(CT)combined with TT and CT alone on advanced BTC.AIM To conduct a meta-analysis of the available evidence on the efficacy of CT combined with TT for advanced BTC.METHODS The PubMed,EMBASE,ClinicalTrials,Scopus and Cochrane Library databases were systematically searched for relevant studies published from inception to August 2022.Only randomized clinical trials(RCTs)including comparisons between the combination of gemcitabine-based CT with TT and CT alone as firstline treatment for advanced BTC were eligible(PROSPERO-CRD42022313001).The odds ratios(ORs)for the objective response rate(ORR)and hazard ratios(HRs)for both progression-free survival(PFS)and overall survival(OS)were calculated and analyzed.Subgroup analyses based on different targeted agents,CT regimens and tumor locations were prespecified.RESULTS Nine RCTs with a total of 1361 individuals were included and analyzed.The overall analysis showed a significant improvement in ORR in patients treated with CT+TT compared to those treated with CT alone(OR=1.43,95%CI:1.11-1.86,P=0.007)but no difference in PFS or OS.Similar trends were observed in the subgroup treated with agents targeting epidermal growth factor receptor(OR=1.67,95%CI:1.17-2.37,P=0.004)but not in the subgroups treated with agents targeting vascular endothelial growth factor receptor or mesenchymal-epithelial transition factor.Notably,patients who received a CT regimen of gemcitabine+oxaliplatin in the CT+TT arm had both a higher ORR(OR=1.75,95%CI:1.20-2.56,P=0.004)and longer PFS(HR=0.83,95%CI:0.70-0.99,P=0.03)than those in the CT-only arm.Moreover,patients with cholangiocarcinoma treated with CT+TT had significantly increased ORR and PFS(ORR,OR=2.06,95%CI:1.27-3.35,PFS,HR=0.79,95%CI:0.66-0.94).CONCLUSION CT+TT is a potential first-line treatment for advanced BTC that leads to improved tumor control and survival outcomes,and highlighting the importance of CT regimens and tumor types in the application of TT.展开更多
We read with great interest the PANDORINA study(1).This international multicenter(mostly from the Netherlands)randomized controlled trial aimed at determining whether omitting drainage after distal pancreatectomy(DP)w...We read with great interest the PANDORINA study(1).This international multicenter(mostly from the Netherlands)randomized controlled trial aimed at determining whether omitting drainage after distal pancreatectomy(DP)was equivalent in terms of complications to systematic drainage placement.The primary outcome was the occurrence of severe complications at 90 days defined as Dindo-Clavien grade≥3.The main secondary outcome was the occurrence of grade B–C postoperative pancreatic fistula(POPF)at 90 days.For both outcomes,the non-inferiority threshold was set at 8%.Randomization was performed intraoperatively,stratified by annual center volume(high volume defined as DP≥40/year)and the risk of POPF according to the distal fistula risk score(D-FRS)combining pancreas thickness(high risk,>19 mm)and main pancreatic duct diameter(high risk,>3 mm)measured both at the isthmus(2).展开更多
目的：评价胸腔闭式引流术后胸膜腔内注入榄香烯治疗恶性胸腔积液的有效性.方法：检索MEDLINE（1996年1月至2010年10月）、中国生物医学文献数据库（1978年1月至2010年10月）、中国期刊全文数据库（1994年至2010年）、万方数据库（1980...目的：评价胸腔闭式引流术后胸膜腔内注入榄香烯治疗恶性胸腔积液的有效性.方法：检索MEDLINE（1996年1月至2010年10月）、中国生物医学文献数据库（1978年1月至2010年10月）、中国期刊全文数据库（1994年至2010年）、万方数据库（1980年至2010年）与重庆维普信息数据库（1989年至2010年）共5个数据库,同时从参考文献中追溯文献,并收集未发表的文献.纳入胸腔闭式引流术后,胸膜腔内注入榄香烯治疗恶性胸腔积液的随机对照试验,使用Cochrane中心推荐的方法进行文献质量评价,并用Rev Man 5.0软件进行统计分析.结果：共纳入17篇文献,16篇文献的方法学质量较低.其中12项独立研究对胸腔闭式引流术＋榄香烯与胸腔闭式引流术＋顺铂治疗的临床效果进行比较,合并分析结果显示榄香烯组的有效率高于顺铂组[RR合并=1.26,95%CI（1.13,1.39）].结论：胸膜腔闭式引流术后胸膜腔内注入榄香烯可以提高恶性胸腔积液治疗的有效率.展开更多
目的:评价术前糖预处理结直肠手术后预防胰岛素抵抗的有效性和安全性,为临床实践提供参考。方法:按照系统评价的要求计算机检索中国期刊全文数据库、中国生物医学文献数据库、中文科技期刊数据库、中国医学会数字化期刊库、PubMed、Coch...目的:评价术前糖预处理结直肠手术后预防胰岛素抵抗的有效性和安全性,为临床实践提供参考。方法:按照系统评价的要求计算机检索中国期刊全文数据库、中国生物医学文献数据库、中文科技期刊数据库、中国医学会数字化期刊库、PubMed、Cochrane Library、EMbase、ISI Web of Knowledge,同时手工检索相关期刊,纳入术前糖预处理结直肠手术后预防胰岛素抵抗的随机对照试验,依据Cochrane评价手册5.0标准对纳入文献的方法学质量进行评估,采用RevMan 5.0软件对符合纳入标准的7个随机对照试验进行Meta分析。结果:共纳入7个随机对照研究,共728例患者。在术前口服碳水化合物组较术前常规禁食水组胰岛素敏感指数(ISI)升高(SMD=-0.38,95%CI=-0.65～0.11,I2=94%)和胰岛素抵抗指数(IRI)降低(SMD=-1.82,95%CI=-2.67～-0.98)方面存在差异,但可降低术前患者饥饿感、焦虑感和口渴感。术前口服碳水化合物较术前口服安慰剂可降低IRI(SMD=-1.34,95%CI=-2.12～-0.57),增加ISI(SMD=1.06,95%CI=0.32～1.81),不能降低术前患者的焦虑感和恶心感。术前口服碳水化合物在术后胰岛素水平(SMD=3.51,95%CI=2.99～4.03)和术后第1天胰岛素水平(SMD=0.65,95%CI=0.31～0.98)方面较术前静滴葡萄糖增高幅度大,且延长患者住院时间(SMD=0.45,95%CI=0.12～0.78)。结论:术前口服碳水化合物较术前常规禁食水更可能降低术前患者饥饿感、焦虑感和口渴感;术前口服碳水化合物较术前口服安慰剂更可能降低IRI和ISI;术前静滴葡萄糖较术前口服碳水化合物更可能增高术后胰岛素敏感程度,且降低患者住院时间。展开更多
基金Supported by Research support from Alberta Innovates Health Solutions, Canadian Institutes for Health Research (to Mason AL, MOP 97798)Canadian Liver Foundation relevant to this manuscript
文摘Following the characterization of a human betaretrovirus in patients with primary biliary cirrhosis(PBC),pilot studies using antiretroviral therapy have been conducted as proof of principal to establish a link of virus with disease and with the eventual aim to find better adjunct therapies for patients unresponsive to ursodeoxycholic acid.In the first open label pilot study,the reverse transcriptase inhibitor lamivudine had little demonstrable biochemical or histological effect after 1 year.Whereas,lamivudine in combination with zidovudine was associated with a significant reduction in alkaline phosphatase as well as improvement in necroinflammatory score,cholangitis and ductopenia over a 12 mo period.A double blind,multi-center randomized controlled trial using lamivudine with zidovudine for 6 mo confirmed a significant reduction in alkaline phosphatase,ALT and AST in patients on antiviral therapy.However,none of the patients achieved the stringent endpoint criteria for normalization of alkaline phosphatase.Furthermore,some patients developed biochemical rebound consistent with drug resistance.A major fault of these studies has been the inability to measure the viral load in peripheral blood and therefore,provide a direct correlation between improvement of hepatic biochemistry and reduction in viral load.Nevertheless,viral mutants to lamivudine with zidovudine were later characterized in the NOD.c3c4 mouse model of PBC that has been used to test other antiretroviral regimens to betaretrovirus.The combination of tenofovir and emtricitabine reverse transcriptase inhibitors and the HIV protease inhibitor,lopinavir were found to abrogate cholangitis in the NOD.c3c4 mouse model and the same regimen normalized the liver tests in a PBC patient with HIV and human betaretrovirus infection.This combination antiretroviral therapy has now been used in a double blind randomized controlled crossover study for patients with PBC followed by an open label extension study.Only a third of the PBC patients were able to tolerate the lopinavir but those maintained on tenofovir,emtricitabine and lopinavir experienced sustained and clinically meaningful reduction in hepatic biochemistry.While we await the histological and virological evaluation,it is clear that better tolerated regimens of antiretroviral treatment will be required in future clinical trials.
基金Supported by China Academy of Medical Science Innovation Fund for Medical Sciences,CIFMS,No.2021-I2M-1-022-2021-S4.
文摘BACKGROUND Targeted therapy(TT)has resulted in controversial efficacy as first-line treatment for biliary tract cancer(BTC).More efficacy comparisons are required to clarify the overall effects of chemotherapy(CT)combined with TT and CT alone on advanced BTC.AIM To conduct a meta-analysis of the available evidence on the efficacy of CT combined with TT for advanced BTC.METHODS The PubMed,EMBASE,ClinicalTrials,Scopus and Cochrane Library databases were systematically searched for relevant studies published from inception to August 2022.Only randomized clinical trials(RCTs)including comparisons between the combination of gemcitabine-based CT with TT and CT alone as firstline treatment for advanced BTC were eligible(PROSPERO-CRD42022313001).The odds ratios(ORs)for the objective response rate(ORR)and hazard ratios(HRs)for both progression-free survival(PFS)and overall survival(OS)were calculated and analyzed.Subgroup analyses based on different targeted agents,CT regimens and tumor locations were prespecified.RESULTS Nine RCTs with a total of 1361 individuals were included and analyzed.The overall analysis showed a significant improvement in ORR in patients treated with CT+TT compared to those treated with CT alone(OR=1.43,95%CI:1.11-1.86,P=0.007)but no difference in PFS or OS.Similar trends were observed in the subgroup treated with agents targeting epidermal growth factor receptor(OR=1.67,95%CI:1.17-2.37,P=0.004)but not in the subgroups treated with agents targeting vascular endothelial growth factor receptor or mesenchymal-epithelial transition factor.Notably,patients who received a CT regimen of gemcitabine+oxaliplatin in the CT+TT arm had both a higher ORR(OR=1.75,95%CI:1.20-2.56,P=0.004)and longer PFS(HR=0.83,95%CI:0.70-0.99,P=0.03)than those in the CT-only arm.Moreover,patients with cholangiocarcinoma treated with CT+TT had significantly increased ORR and PFS(ORR,OR=2.06,95%CI:1.27-3.35,PFS,HR=0.79,95%CI:0.66-0.94).CONCLUSION CT+TT is a potential first-line treatment for advanced BTC that leads to improved tumor control and survival outcomes,and highlighting the importance of CT regimens and tumor types in the application of TT.
文摘We read with great interest the PANDORINA study(1).This international multicenter(mostly from the Netherlands)randomized controlled trial aimed at determining whether omitting drainage after distal pancreatectomy(DP)was equivalent in terms of complications to systematic drainage placement.The primary outcome was the occurrence of severe complications at 90 days defined as Dindo-Clavien grade≥3.The main secondary outcome was the occurrence of grade B–C postoperative pancreatic fistula(POPF)at 90 days.For both outcomes,the non-inferiority threshold was set at 8%.Randomization was performed intraoperatively,stratified by annual center volume(high volume defined as DP≥40/year)and the risk of POPF according to the distal fistula risk score(D-FRS)combining pancreas thickness(high risk,>19 mm)and main pancreatic duct diameter(high risk,>3 mm)measured both at the isthmus(2).
文摘目的：评价胸腔闭式引流术后胸膜腔内注入榄香烯治疗恶性胸腔积液的有效性.方法：检索MEDLINE（1996年1月至2010年10月）、中国生物医学文献数据库（1978年1月至2010年10月）、中国期刊全文数据库（1994年至2010年）、万方数据库（1980年至2010年）与重庆维普信息数据库（1989年至2010年）共5个数据库,同时从参考文献中追溯文献,并收集未发表的文献.纳入胸腔闭式引流术后,胸膜腔内注入榄香烯治疗恶性胸腔积液的随机对照试验,使用Cochrane中心推荐的方法进行文献质量评价,并用Rev Man 5.0软件进行统计分析.结果：共纳入17篇文献,16篇文献的方法学质量较低.其中12项独立研究对胸腔闭式引流术＋榄香烯与胸腔闭式引流术＋顺铂治疗的临床效果进行比较,合并分析结果显示榄香烯组的有效率高于顺铂组[RR合并=1.26,95%CI（1.13,1.39）].结论：胸膜腔闭式引流术后胸膜腔内注入榄香烯可以提高恶性胸腔积液治疗的有效率.
文摘目的:评价术前糖预处理结直肠手术后预防胰岛素抵抗的有效性和安全性,为临床实践提供参考。方法:按照系统评价的要求计算机检索中国期刊全文数据库、中国生物医学文献数据库、中文科技期刊数据库、中国医学会数字化期刊库、PubMed、Cochrane Library、EMbase、ISI Web of Knowledge,同时手工检索相关期刊,纳入术前糖预处理结直肠手术后预防胰岛素抵抗的随机对照试验,依据Cochrane评价手册5.0标准对纳入文献的方法学质量进行评估,采用RevMan 5.0软件对符合纳入标准的7个随机对照试验进行Meta分析。结果:共纳入7个随机对照研究,共728例患者。在术前口服碳水化合物组较术前常规禁食水组胰岛素敏感指数(ISI)升高(SMD=-0.38,95%CI=-0.65～0.11,I2=94%)和胰岛素抵抗指数(IRI)降低(SMD=-1.82,95%CI=-2.67～-0.98)方面存在差异,但可降低术前患者饥饿感、焦虑感和口渴感。术前口服碳水化合物较术前口服安慰剂可降低IRI(SMD=-1.34,95%CI=-2.12～-0.57),增加ISI(SMD=1.06,95%CI=0.32～1.81),不能降低术前患者的焦虑感和恶心感。术前口服碳水化合物在术后胰岛素水平(SMD=3.51,95%CI=2.99～4.03)和术后第1天胰岛素水平(SMD=0.65,95%CI=0.31～0.98)方面较术前静滴葡萄糖增高幅度大,且延长患者住院时间(SMD=0.45,95%CI=0.12～0.78)。结论:术前口服碳水化合物较术前常规禁食水更可能降低术前患者饥饿感、焦虑感和口渴感;术前口服碳水化合物较术前口服安慰剂更可能降低IRI和ISI;术前静滴葡萄糖较术前口服碳水化合物更可能增高术后胰岛素敏感程度,且降低患者住院时间。
