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| 1 | 钠-葡萄糖共转运蛋白-2抑制剂或胰高血糖素样肽-1受体激动剂治疗成人2型糖尿病:临床实践指南显示文摘临床问题对于存在不同心血管风险及肾脏结局的2型糖尿病患者,在原有生活方式干预和/或其他降糖药物的基础上加用钠-葡萄糖共转运蛋白2(SGLT-2)抑制剂和胰高血糖素样肽1(GLP-1)受体激动剂的获益及风险是什么?现行做法几十年来,2型糖尿病的治疗决策都以控制血糖为主导。SGLT-2抑制剂和GLP-1受体激动剂在传统观念中常被用于二甲双胍治疗后血糖仍控制不佳的患者。目前这一现状已经发生了改变,这得益于多项临床研究结果。研究显示SGLT-2抑制剂和GLP-1受体激动剂拥有独立于药物降糖作用之外的对于动脉粥样硬化性心血管病(CVD)和慢性肾脏病(CKD)的获益。建议本指南阐述了针对不同风险分层的成人2型糖尿病患者使用SGLT-2抑制剂或GLP-1受体激动剂的建议。•伴有3种或更少的心血管风险因素且不存在CVD或CKD:不建议启动SGLT-2抑制剂或GLP-1受体激动剂治疗。(推荐等级:弱)•伴有3种以上心血管风险因素且不存在CVD或CKD:建议启动SGLT-2抑制剂治疗,不建议启动GLP-1受体激动剂治疗。(推荐等级:弱)•已经存在CVD或CKD:建议启动SGLT-2抑制剂治疗和GLP-1受体激动剂治疗。(推荐等级:弱)•已经存在CVD和CKD:建议启动SGLT-2抑制剂治疗(推荐等级:强)和GLP-1受体激动剂治疗。(推荐等级:弱)•对于那些想要进一步降低CVD和CKD结局风险的患者:推荐优先启用SGLT-2抑制剂治疗而非GLP-1受体激动剂治疗。(推荐等级:弱)这项指南是如何制订的一个由患者、临床医生和方法学家共同组成的国际小组提出了这些推荐意见。这些推荐意见基于可信度较高的指南的标准,并使用GRADE分级方法进行评估。该小组采用了息者个体化的观点。证据一项关于获益与风险的系统综述和网络meta分析(764项随机对照研究,包括421346例参与者)发现SGLT-2抑制剂和GLP-1受体激动剂可以降低总体死亡率、心肌梗死发生率、终末期肾病或肾衰竭的发生率(中等至高等质量的证据)。在不同的亚组中这些药物对卒中、因心力衰竭所致住院和其他主要不良事件有不同的影响。药物绝对获益的程度因患者个体风险的不同有很大的差异。(例如,对于接受了超过5年药物治疗的1000例患者,在最低风险人群中死亡人数减少了5人,在最高风险人群中死亡人数减少了48人)。一项关于预后的综述确认了14种风险预测模型,其中一种(RECODe)在证据总结中报告了大部分基线风险评估数据,小组利用该模型以支持风险分层的建议。考虑到患者的价值观及个体差异,指南推荐的支撑证据包括一项对已发表论文的系统综述、一项患者焦点小组研究、一项临床问题总结,以及一项指南调查。指南解读我们依据不同的CVD和CKD风险水平,综合考虑获益、风险和其他因素的平衡,以及每一个风险组别的实际问题,来对推荐意见进行分层。本指南强烈建议CVD和CKD患者使用SGLT-2抑制剂治疗,这说明专家组认为其具有显著的获益。而对于其他成人2型糖尿病患者,推荐等级较弱,这说明专家组想要在获益、风险及治疗花费上取得一个更好的平衡。临床医生通过该指南可以使用可靠的风险计算模型,如RECODe,来明确其患者的个体心血管和肾脏疾病风险。医患交互式总结临床证据和制订决策有助于患者知晓治疗选择,包括进行共同决策。2型糖尿病人群(全球患病率不断增长1-2)正面临着不断增加的心血管疾病、肾脏病和其他并发症的风险3。数十年来,2型糖尿病的管理始终以控制血糖及糖化血红蛋白(HbA1c)为治疗目标4-5,但是,最近的高质量随机对照研究已经对这种以血糖为中心的治疗模式发起了挑战。研究结果显示,强化血糖控制未必会降低大血管不良事件,它还可能带来不利影响监管机构现在要求新型糖尿病药物必须证明其具有心血管和肾脏获益才能获得批准。对两类新药--钠-葡萄糖共转运蛋白2(SGLT-2)抑制剂和胰高血糖素样肽1(GLP-1)受体激动剂(见框图1)的临床试验结果显示,在现有治疗方案(常规治疗)之上加用这些药物,对死亡、心肌梗死、卒中、心力衰竭和肾脏的结局(如进展为终末期肾病)都有获益8-12。 | Sheyu Li Per Olav Vandvik Lyubov Lytvyn Gordon H Guyatt Suetonia C Palmer Rene Rodriguez-Gutierrez Farid Foroutan Thomas Agoritsas Reed A C Siemieniuk Michael Walsh Lawrie Frere David J Tunnicliffe Evi V Nagler Veena Manja Bjφrn Olav Asvold Vivekanand Jha Mieke Vermandere Karim Gariani Qian Zhao Yan Ren Emma Jane Cartwright Patrick Gee Alan Wickes Linda Fems Robin Wright Ling Li Qiukui Hao Reem A Mustafa 无 郭鹤鸣(译) | 2021 | 英国医学杂志中文版2021，24，9： | 7 |
| 2 | Efficacy and safety of tenofovir in chronic hepatitis B: Australian real world experience显示文摘AIM To evaluate the long-term treatment outcomes of tenofovir therapy in patients in a real world Australian tertiary care setting.METHODS We performed a retrospective analysis of treatment outcomes among treatment-na?ve and treatment-experienced patients receiving a minimum 3 mo tenofovir therapy through St Vincent's Hospital Melbourne, Australia. We included patients receiving tenofovir [tenofovir disoproxil fumarate(TDF)] monotherapy, as well as patients treated with TDF in combination with a second antiviral agent. Patients were excluded if they demonstrated human immune-deficiency virus/hepatitis C virus/hepatitis delta virus coinfection or were less than 18 years of age. We considered virological and biochemicalresponse, as well as safety outcomes. Virological response was determined by measurement of hepatitis B virus(HBV) DNA using sensitive assays; biochemical response was determined via serum liver function tests; histological response was determined from liver biopsy and fibroscan; safety analysis focused on glomerular renal function and bone mineral density. The primary efficacy endpoint was complete virological suppression over time, defined by HBV DNA < 20 IU/m L. Secondary efficacy endpoints included rates of biochemical response, and HB e antigen(HBe Ag)/HB surface antigen loss and seroconversion over time.RESULTS Ninety-two patients were identified who fulfilled the enrolment criteria. Median follow-up was 26 mo(range 3-114). Mean age was 46(24-78) years, 64(70%) were male and 77(84%) were of Asian origin. 55(60%) patients were treatment-na?ve and 62 patients(67%) were HBe Ag-negative. Complete virological suppression was achieved by 45/65(71%) patients at 12 mo, 37/46(80%) at 24 mo and 25/28(89%) at 36 mo. Partial virological response(HBV DNA 20-2000 IU/m L) was achieved by 89/92(96.7%) of patients. Multivariate analysis showed a significant relationship between virological suppression at end of follow-up and baseline HBV DNA level(OR = 0.897, 95%CI: 0.833-0.967, P = 0.0046) and HBe Ag positive status(OR = 0.373, 95%CI: 0.183-0.762, P = 0.0069). There was no difference in response comparing treatment-na?ve and treatment-experienced patients. Three episodes of virological breakthrough occurred in the setting of noncompliance. Tenofovir therapy was well tolerated.CONCLUSION Tenofovir is an efficacious, safe and well-tolerated treatment in an Australian real-world tertiary care setting. Our data are similar to the reported experience from registration trials. | Grace C Lovett Tin Nguyen David M Iser Jacinta A Holmes Robert Chen Barbara Demediuk Gideon Shaw Sally J Bell Paul V Desmond Alexander J Thompson | 2017 | World Journal of Hepatology2017，9，1： | 7 |
| 3 | Dynamic chromatin states in human ES cells reveal potential regulatory sequences and genes involved in pluripotency显示文摘Pluripotency,一个细胞的能力区分并且产生所有胚胎的系,定义象胚胎的茎(ES ) 那样的哺乳动物的细胞类型的一个小数字细胞。当它通常被保持了时,那 pluripotency 是 transcriptional 的产品激活并且维持关键干细胞基因的表达式的规章的网络,积累的证据在建立并且保卫 ES 房间的 pluripotency 为 epigenetic 进程正在指向一个关键角色,象维持区分的房间类型的身份一样。以便更好在 pluripotency 理解 epigenetic 机制的角色,我们检验了在经历区别进一个 mesendodermal 系的人的 ES 房间(hESCs ) 染色体宽的染色质修正的动力学。我们发现在倡导者的染色质修正在区别期间仍然保持大部分不变,除了在在在 H3K27 的 acetylation 和 methylation 之间的一个动态开关标记在基因表示的激活和 silencing 之间的转变的倡导者的一个小数字,建议在在大多数差别上的房间命运承诺的一个层次表示了基因。我们也在 50 000 潜在的 enhancers 上印射,并且在染色质修正,特别 H3K4me1 和 H3K27ac 观察了大得多的动力学,它与他们的潜在的目标基因的表示相关。这些 enhancers 的进一步的分析揭示了 pluripotency 和可以在 hESCs 授与发展胜任的一个平衡状态的一口染色质签名陈述语气的潜在地关键的 transcriptional 管理者。我们的结果提供在定义 enhancers 和 pluripotency 支持染色质修正的角色的新证据。 | R David Hawkins Gary C Hon Chuhu Yang Jessica E Antosiewicz-Bourget Leonard K Lee Que-Minh Ngo Sarit Klugman Keith A Ching Lee E Edsall Zhen Ye Samantha Kuan Pengzhi Yu Hui Liu Xinmin Zhang Roland D Green Victor V Lobanenkov Ron Stewart James A Thomson Bing Ren | 2011 | Cell Research2011，21，10： | 6 |
| 4 | Acute liver injury induced by weight-loss herbal supplements显示文摘We report three cases of patients with acute liver injury induced by weight-loss herbal supplements. One patient took Hydroxycut while the other two took Herbalife supplements. Liver biopsies for all patients dem onstrated f indings consistent with drug-induced acute liver injury. To our knowledge, we are the fi rst instit ute to report acute liver injury from both of these two typ es of weight-loss herbal supplements together as a case series. The series emphasizes the importance of taking a cautious approach when consuming herbal supp lements for the purpose of weight loss. | Gary C Chen Vivek S Ramanathan David Law Pauline Funchain George C Chen Samuel French Boris Shlopov Viktor Eysselein David Chung Sonya Reicher Binh V Pham | 2010 | World Journal of Hepatology2010，2，11： | 5 |
| 5 | Approach to medical therapy in perianal Crohn’s disease显示文摘Perianal Crohn’s disease remains a challenging condition to treat and can have a substantial negative impact on quality of life.It often requires combined surgical and medical interventions.Anti-tumor necrosis factor(anti-TNF)therapy,including infliximab and adalimumab,remain preferred medical therapies for perianal Crohn’s disease.Infliximab has been shown to be efficacious in improving fistula closure rates in randomized controlled trials.Clinicians can be faced with a number of questions relating to the optimal use of anti-TNF therapy in perianal Crohn’s disease.Specific issues include evaluation for the presence of perianal sepsis,the treatment target of therapy,the ideal time to commence treatment,whether additional medical therapy should be used in conjunction with anti-TNF therapy,and the duration of treatment.This article will discuss key studies which can assist clinicians in addressing these matters when they are considering or have already commenced anti-TNF therapy for the treatment of perianal Crohn’s disease.It will also discuss current evidence regarding the use of vedolizumab and ustekinumab in patients who are failing to achieve a response to anti-TNF therapy for perianal Crohn’s disease.Lastly,new therapies such as local injection of mesenchymal stem cell therapy will be discussed. | Abhinav Vasudevan David H Bruining Edward V Loftus Jr William Faubion Eric C Ehman Laura Raffals | 2021 | World Journal of Gastroenterology2021，27，25： | 4 |
| 6 | MicroRNA profile in neosquamous esophageal mucosa following ablation of Barrett's esophagus显示文摘AIM To investigate the micro RNA expression profile in esophageal neosquamous epithelium from patients who had undergone ablation of Barrett's esophagus.METHODS High throughput screening using Taq Man~ Array Human Micro RNA quantitative PCR was used to determine expression levels of 754 micro RNAs in distal esophageal mucosa(1 cm above the gastro-esophageal junction) from 16 patients who had undergone ablation of non-dysplastic Barrett's esophagus using argon plasma coagulation vs pretreatment mucosa, posttreatment proximal normal non-treated esophageal mucosa, and esophageal mucosal biopsies from 10 controls without Barrett's esophagus. Biopsies of squamous mucosa were also taken from 5 cm above the pre-ablation squamo-columnar junction. Predicted m RNA target pathway analysis was used to investigate the functional involvement of differentially expressed micro RNAs.RESULTS Forty-four micro RNAs were differentially expressed between control squamous mucosa vs post-ablation neosquamous mucosa. Nineteen micro RNAs were differentially expressed between post-ablation neosquamous and post-ablation squamous mucosa obtained from the more proximal non-treated esophageal segment. Twelve microRNAs were differentially expressed in both neosquamous vs matched proximal squamous mucosa and neosquamous vs squamous mucosa from healthy patients. Nine micro RNAs(mi R-424-5p, mi R-127-3p, mi R-98-5p, mi R-187-3p, mi R-495-3p, mi R-34c-5p, mi R-223-5p, mi R-539-5p, mi R-376a-3p, mi R-409-3p) were expressed at higher levels in post-ablation neosquamous mucosa than in matched proximal squamous and healthy squamous mucosa. These micro RNAs were also more highly expressed in Barrett's esophagus mucosa than matched proximal squamous and squamous mucosa from controls. Target prediction and pathway analysis suggests that these micro RNAs may be involved in the regulation of cell survival signalling pathways. Three micro RNAs(mi R-187-3p, mi R-135b-5p and mi R-31-5p) were expressed at higher levels in postablation neosquamous mucosa than in matched proximal squamous and healthy squamous mucosa. These mi RNAs were expressed at similar levels in preablation Barrett's esophagus mucosa, matched proximal squamous and squamous mucosa from controls. Target prediction and pathway analysis suggests that these micro RNAs may be involved in regulating the expression of proteins that contribute to barrier function.CONCLUSION Neosquamous mucosa arising after ablation of Barrett's esophagus expresses micro RNAs that may contribute to decreased barrier function and micro RNAs that may be involved in the regulation of survival signaling pathways. | Loveena Sreedharan George C Mayne David I Watson Timothy Bright Reginald V Lord Alfiya Ansar Tingting Wang Jakob Kist David StJ Astill Damian J Hussey | 2017 | World Journal of Gastroenterology2017，23，30： | 3 |
| 7 | Sofosbuvir with pegylated interferon alfa-2a and ribavirin for treatment-naive patients with hepatitis C genotype-1 infection (ATOMIC): an open-label, randomised, multicentre phase 2 trial显示文摘 | Kris V Kowdley Eric Lawitz Israel Crespo Tarek Hassanein Mitchell N Davis Michael DeMicco David E Bernstein Nezam Afdhal John M Vierling Stuart C Gordon Jane K Anderson Robert H Hyland Hadas Dvory-Sobol Di An Robert G Hindes Efsevia Albanis William T Symo | 2013 | The Lancet2013，，9883： | 3 |
| 8 | Para-aortic lymph node involvement should not be a contraindication to resection of pancreatic ductal adenocarcinoma显示文摘BACKGROUND Para-aortic lymph nodes(PALN)are found in the aortocaval groove and they are staged as metastatic disease if involved by pancreatic ductal adenocarcinoma(PDAC).The data in the literature is conflicting with some studies having associated PALN involvement with poor prognosis,while others not sharing the same results.PALN resection is not included in the standard lymphadenectomy during pancreatic resections as per the International Study Group for Pancreatic Surgery and there is no consensus on the management of these cases.AIM To investigate the prognostic significance of PALN metastases on the oncological outcomes after resection for PDAC.METHODS This is a retrospective cohort study of data retrieved from a prospectively maintained database on consecutive patients undergoing pancreatectomies for PDAC where PALN was sampled between 2011 and 2020.Statistical comparison of the data between PALN+and PALN-subgroups,survival analysis with the Kaplan-Meier method and risk analysis with univariable and multivariable time to event Cox regression analysis were performed,specifically assessing oncological outcomes such as median overall survival(OS)and disease-free survival(DFS).RESULTS 81 cases had PALN sampling and 17(21%)were positive.Pathological N stage was significantly different between PALN+and PALN-patients(P=0.005),while no difference was observed in any of the other characteristics.Preoperative imaging diagnosed PALN positivity in one case.OS and DFS were comparable between PALN+and PALN-patients with lymph node positive disease(OS:13.2 mo vs 18.8 mo,P=0.161;DFS:13 mo vs 16.4 mo,P=0.179).No difference in OS or DFS was identified between PALN positive and negative patients when they received chemotherapy either in the neoadjuvant or in the adjuvant setting(OS:23.4 mo vs 20.6 mo,P=0.192;DFS:23.9 mo vs 20.5 mo,P=0.718).On the contrary,when patients did not receive chemotherapy,PALN disease had substantially shorter OS(5.5 mo vs 14.2 mo;P=0.015)and DFS(4.4 mo vs 9.8 mo;P<0.001).PALN involvement was not identified as an independent predictor for OS after multivariable analysis,while it was for DFS doubling the risk of recurrence.CONCLUSION PALN involvement does not affect OS when patients complete the indicated treatment pathway for PDAC,surgery and chemotherapy,and should not be considered as a contraindication to resection. | Rupaly Pande Shafiq Chughtai Manish Ahuja Rachel Brown David C Bartlett Bobby V Dasari Ravi Marudanayagam Darius Mirza Keith Roberts John Isaac Robert P Sutcliffe Nikolaos A Chatzizacharias | 2022 | World Journal of Gastrointestinal Surgery2022，14，5： | 2 |
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