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| 1 | 帕博利珠单抗单用或与放疗联用治疗转移性非小细胞肺癌:两个随机试验的汇总分析显示文摘背景放疗可以提高整个机体对免疫治疗的应答。在Ⅱ期PEMBRO-RT研究和Ⅰ/Ⅱ期MDACC研究中,患有转移性非小细胞肺癌(NSCLC)的患者被随机分配入组,接受免疫治疗(帕博利珠单抗)+放疗联合疗法,或免疫治疗单一疗法。当上述2个研究单独分析时,联合疗法组显示出潜在获益。由于每个研究的样本量较小,缓解率和结局并未显示出统计学意义,然而却有显著的临床获益。因此,本研究进行汇总分析,来判断放疗是否会改善转移性NSCLC患者的免疫治疗应答。方法PEMBRO-RT和MDACC研究纳入标准:患者年龄≥18岁,患有转移性NSCLC,且有≥1处未经放疗照射的病灶,以便进行射野外应答监测。PEMBRO-RT研究纳入曾接受过化疗患者,MDACC研究纳入曾接受过治疗或新诊断患者。2个研究中的患者均未接受过免疫治疗。在PEMBRO-RT研究中患者被等比例随机分配入组,并根据吸烟状态进行分层(分为<10年组和≥10年组)。MDACC研究的患者根据放疗计划可行性被等比例随机分配入2个受试组。由于联合治疗组的干预本质,每个研究中的放疗均不适用盲法。在2个研究中,不论是否进行放疗,均静脉滴入帕博利珠单抗(每3周200 mg)。在PEMBRO-RT研究中,在放疗(24 Gy 3次分割照射)结束后1周给予第1剂帕博利珠单抗。在MDACC研究中,在第1次放疗(50 Gy 4次分割照射或45 Gy 15次分割照射)同时给予帕博利珠单抗。仅检测未经照射病灶的应答。本研究的终点为最佳射野外(远隔)应答率(ARR)、最佳射野外疾病控制率(ACR)、12周时ARR、12周时ACR、无进展生存期(PFS)和总生存期(OS)。2个研究的意向治疗(ITT)人群均纳入分析。PEMBRO-RT研究(NCT02492568)和MDACC研究(NCT02444741)均在ClinicalTrials.gov上注册。发现纳入148例患者,76例接受帕博利珠单抗治疗,72例接受帕博利珠单抗+放疗治疗。所有患者随访时间中位数为33个月[四分位距(IQR):32.4~33.6]。148例患者中124例(84%)组织学特征为非鳞癌,111例(75%)患者曾经接受过化疗。组间没有基线特征差异,包括PD-L1表达状态和转移灶体积。最常见的照射部位为肺转移灶(39%,28/72)、胸腔内淋巴结(21%,15/72)和非原发灶(17%,12/72)。帕博利珠单抗组和联合治疗组的最佳ARR分别为19.7%(15/76)和41.7%(30/72),OR=2.96,95%CI:1.42~6.20,P=0.0039;最佳ACR分别为43.4%(33/76)和65.3%(47/72),OR=2.51,95%CI:1.28~4.91,P=0.0071;PFS中位数分别为4.4(IQR:2.9~5.9)和9.0个月(IQR:6.8~11.2),HR=0.67,95%CI:0.45~0.99,P=0.045;OS中位数分别为8.7(IQR:6.4~11.0)和19.2个月(IQR:14.6~23.8),OR=0.67,95%CI:0.54~0.84,P=0.0004。在汇总分析中没有发现新的安全问题。解读帕博利珠单抗免疫疗法+放疗显著提高转移性NSCLC患者的应答和改善治疗结局。这些结果需要在三期临床试验中进行验证。 | 陈大卫(翻译) 于金明(校对) Willemijn S M E Theelen Vivek Verma Brian P Hobbs Heike M U Peulen Joachim G J V Aerts Idris Bahce Anna Larissa N Niemeijer Joe Y Chang Patricia M de Groot Quynh-Nhu Nguyen Nathan I Comeaux George R Simon Ferdinandos Skoulidis Steven H Lin Kewen He Roshal Patel John Heymach Paul Baas James W Welsh | 2021 | 中华肿瘤防治杂志2021，28，24： | 49 |
| 2 | Lipids in liver transplant recipients显示文摘Hyperlipidemia is very common after liver transplantation and can be observed in up to 71% of patients. The etiology of lipid disorders in these patients is multifactorial, with different lipid profiles observed depending on the immunosuppressive agents administered and the presence of additional risk factors, such as obesity, diabetes mellitus and nutrition. Due to recent improvements in survival of liver transplant recipients, the prevention of cardiovascular events has become more important, especially as approximately 64% of liver transplant recipients present with an increased risk of cardiovascular events. Management of dyslipidemia and of other modifiable cardiovascular risk factors, such as hypertension, diabetes and smoking, has therefore become essential in these patients. Treatment of hyperlipidemia after liver transplantation consists of life style modification, modifying the dose or type of immunosuppressive agents and use of lipid lowering agents. At the start of administration of lipid lowering medications, it is important to monitor drugdrug interactions, especially between lipid lowering agents and immunosuppressive drugs. Furthermore, as combinations of various lipid lowering drugs can lead to severe side effects, such as myopathies and rhabdomyolysis, these combinations should therefore be avoided. To our knowledge, there are no current guidelines targeting the management of lipid metabolism disorders in liver transplant recipients. This paper therefore recommends an approach of managing lipid abnormalities occurring after liver transplantation. | anna hüsing iyad kabar hartmut h schmidt | 2016 | World Journal of Gastroenterology2016，22，12： | 6 |
| 3 | Single-operator cholangioscopy for biliary complications in liver transplant recipients显示文摘AIM To evaluate cholangioscopy in addition to endoscopic retrograde cholangiopancreatography(ERCP) for management of biliary complications after liver transplantation(LT).METHODS Twenty-six LT recipients with duct-to-duct biliary reconstruction who underwent ERCP for suspected biliary complications between April and December2016 at the university hospital of Muenster were consecutively enrolled in this observational study. After evaluating bile ducts using fluoroscopy, cholangioscopy using a modern digital single-operator cholangioscopy s y s t e m(S py G la s s D S ?) wa s pe r fo r me d dur ing the same procedure with patients under conscious sedation. All patients received peri-interventional antibiotic prophylaxis and bile was collected during the intervention for microbial analysis and for antibiotic susceptibility testing.RESULTS Thirty-three biliary complications were found in a total of 22 patients, whereas four patients showed normal bile ducts. Anastomotic strictures were evident in 14(53.8%) patients, non-anastomotic strictures in seven(26.9%), biliary cast in three(11.5%), and stones in six(23.1%). A benefit of cholangioscopy was seen in 12(46.2%) patients. In four of them, cholangioscopy was crucial for selective guidewire placement prior to planned intervention. In six patients, biliary cast and/or stones failed to be diagnosed by ERCP and were only detectable through cholangioscopy. In one case, a bile duct ulcer due to fungal infection was diagnosed by cholangioscopy. In another case, signs of bile duct inflammation caused by acute cholangitis were evident. One patient developed post-interventional cholangitis. No further procedure-related complications occurred. Thirty-seven isolates were found in bile. Sixteen of these were gram-positive(43.2%), 12(32.4%) were gram-negative bacteria, and Candida species accounted for 24.3% of all isolated microorganisms. Interestingly, only 48.6% of specimens were sensitive to prophylactic antibiotics.CONCLUSION Single-operator cholangioscopy can provide important diagnostic information, helping endoscopists to plan and perform interventional procedures in LT-related biliary complications. | Anna Hüsing-Kabar Hauke Sebastian Heinzow Hartmut Hans-Jürgen Schmidt Carina Stenger Hans Ulrich Gerth Michele Pohlen Gerold Tholking Christian Wilms Iyad Kabar | 2017 | World Journal of Gastroenterology2017，23，22： | 4 |
| 4 | Steatosis and steatohepatitis in postmortem material from Northwestern Greece显示文摘AIM: To determine the prevalence of steatosis and steatohepatitis in a series of autopsies in Northwestern Greece. METHODS: Liver biopsy material from a total of 600 autopsies performed over a period of 2 years (2006-2008) to def ine the cause of death was subjected to histological examination. Patient demographic data were also collected. Tissue sections were stained with different dyes for the evaluation of liver architecture, degree of fibrosis and other pathological conditions when necessary. RESULTS: Satisfactory tissue samples for histological evaluation were available in 498 cases (341 male, 157 female) with a mean age of 64.51 ± 17.78 years. In total, 144 (28.9%) had normal liver histology, 156 (31.3%) had evidence of steatosis, and 198 (39.8%) had typical histological findings of steatohepatitis. The most common causes of death were ischemic heart disease with or without myocardial infarction (43.4%), and traffic accidents (13.4%). CONCLUSION: A high prevalence of steatosis and steatohepatitis was detected in postmortem biopsies from Northwestern Greece. Since both diseases can have serious clinical consequences, they should be considered as an important threat to the health of the general population in Greece. | Christos D Zois Gerasimos H Baltayiannis Anna Bekiari Anna Goussia Peter Karayiannis Michalis Doukas Demetrios Demopoulos Antigoni Mitsellou Theodoros Vougiouklakis Vasiliki Mitsi Epameinondas V Tsianos | 2010 | World Journal of Gastroenterology2010，16，31： | 4 |
| 5 | Paclitaxel-eluting balloon dilation of biliary anastomotic stricture after liver transplantation显示文摘AIM:To investigate the safety and effectiveness of endoscopic therapy with a paclitaxel-eluting balloon(PEB) for biliary anastomotic stricture(AS) after liver transplantation(LT).METHODS:This prospective pilot study enrolled 13 consecutive eligible patients treated for symptomatic AS after LT at the University Hospital of Münster between January 2011 and March 2014.The patients were treated by endoscopic therapy with a PEB and followed up every 8 wk by endoscopic retrograde cholangiopancreatography(ERCP).In cases of re-stenosis,further balloon dilation with a PEB was performed.Follow-up was continued until 24 mo after the last intervention.RESULTS:Initial technical feasibility,defined as successful balloon dilation with a PEB during the initial ERCP procedure,was achieved in 100% of cases.Long-term clinical success(LTCS),defined as no need for further endoscopic intervention for at least 24 mo,was achieved in 12 of the 13 patients(92.3%).The mean number of endoscopic interventions required to achieve LTCS was only 1.7 ± 1.1.Treatment failure,defined as the need for definitive alternative treatment,occurred in only one patient,who developed recurrent stenosis with increasing bile duct dilatation that required stent placement.CONCLUSION:Endoscopic therapy with a PEB is very effective for the treatment of AS after LT,and seems to significantly shorten the overall duration of endoscopic treatment by reducing the number of interventions needed to achieve LTCS. | Anna Hüsing Holger Reinecke Vito R Cicinnati Susanne Beckebaum Christian Wilms Hartmut H Schmidt Iyad Kabar | 2015 | World Journal of Gastroenterology2015，21，3： | 4 |
| 6 | Variability of platelet aggregation in patients with clopidogrel treatment and hip fracture: A retrospective case-control study on 112 patients显示文摘AIM: To identify the rate of non-responders to clopidogrel treatment in hip fracture patients and study how non-responders differ from controls.METHODS: In a retrospective case-control study we included 28 cases of acute proximal femoral fracture with clopidogrel treatment 2011 to 2013. Eighty-four controls from the same time period were included. Data collected included response to clopidogrel measured with multiple electrode aggregometry(MEA), intraoperative bleeding, erythrocyte transfusion, time to surgery and the incidence of adverse events up to 3 mo after surgery. RESULTS: Eight(29%) of the 28 cases were nonresponders. The median intraoperative bleeding was 300 mL(range, 0-1500), and was lower for non-responders(50 m L) but did not reach statistical significance. Erythrocyte transfusions did not differ between responders, non-responders and controls. Forty-five(40%) of 112 patients had adverse events postoperatively but the rate did not differ between patients with and without clopidogrel treatment.CONCLUSION: Almost one-third of patients withclopidogrel treatment and an acute proximal femoral fracture are non-responders to antiplatelet therapy and can be operated without delay. | Anna Clareus Inga Fredriksson Hkan Wallén Max Gordon André Stark Olof Skldenberg | 2015 | World Journal of Orthopedics2015，6，5： | 4 |
| 7 | Polymer mierocapsules by interfacial polyaddition between styrene-maleic anhydride copolymers and amines显示文摘 | Harald D H Stover | 2002 | Journal of Membrane Science2002，209，2： | 1 |
| 8 | Apoptosis inhibition plays a greater role than necrosis inhibition in decreasing bacterial transloca- tion in experimental intestinal transplantation 显示文摘 | Daniel A Anna S Georgina H | 2005 | Surgery2005，137，1： | 1 |
| 9 | The flame retardant mechanism of polylefins modified with chalk and silicone elastomer显示文摘 | ANNA H THOMAS H BERNT-AKE S | 2003 | Fire and Materials2003，27，2： | 1 |
| 10 | A comparison between the protection of LDH during freeze-thawing by PEG6000 and Brij 35 at low concentrations显示文摘 | Anna H Maggie A | 2002 | Int J Pharm2002，，12： | 1 |
| 11 | Induction of macrophage nitric oxide production by gram-negative flagellin involves signaling via heteromeric Toll-like receptor 5/Toll-like receptor 4 complexes显示文摘 | MIZEL S B ANNA N H MARLENA A M | 2003 | The Journal of Immunology2003，170，： | 1 |
| 12 | Impact of pollen on hu- man health: more than allergen carriers 显示文摘 | Claudia T H Anna K Annette M | 2003 | Allergy Immunol2003，131，： | 1 |
| 13 | Human fear conditioning is related to dopaminergic and serotonergic biological markers显示文摘 | Garpenstrand H Annas P Ekblom J | 2001 | Behav Neurosci2001，115，2： | 1 |
| 14 | Deep sequencing of the zebrafish transcriptome response to mycobacterium infection显示文摘 | Zoltan H Anna Z Vilmos C A | 2009 | Molecular Immunology2009，，46： | 1 |
| 15 | Simultaneous manifestation of fulminant infectious mononucleosis with haemophagocytic syndrome and B-cell lymphoma in X-linked lymphoproliferative disease显示文摘 | Boris Hügle Itziar Astigarraga Jan-Inge Henter Anna Porwit-MacDonald Alfons Meindl Volker Schuster | 2007 | European Journal of Pediatrics2007，，6： | 1 |
| 16 | Drafting the Genetic Privacy Act: Science, Policy and Practical Considerations显示文摘 | Annas G J Glantz L H Roche P A | 1995 | The Journal of Law Medicine and Ethics1995，23，4： | 1 |
| 17 | ADP glucose pyro- phosphorylase is activated by posttranslation at redox - modifica-tlon in response to light and to sugars in leaves of Arabidopsis and other plant species 显示文摘 | Janneke H M Hendriks Anna K | 2003 | Plant Physiology2003，133，： | 1 |
| 18 | Influ- ence of Tai Chi exercise on proprioception in patients with Knee Osteoarthritis: Results from a pilot randomized con- trolled trial显示文摘 | Anna Schmid Timothy McAlindon Christopher H | 2010 | Osteoarthritis and Cartilage2010，18，2： | 1 |
| 19 | Green Chemistry Methods in Sulfur Dyeing: Application of Various Reducing D - Sugars and Analysis of the Importance of Optimum Redox Potential显示文摘 | Richard S B Anna H | 2004 | Environmental science & technology2004，38，14： | 1 |
| 20 | Effects of bacterial cell surface structure and hydrophobie on attachment to activated sludge floes 显示文摘 | Anna Z Malte H | 1997 | Applied and Environment Microbiology1997，63，3： | 1 |
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