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Interpatient heterogeneity in hepatic microvascular blood flow during vascular inflow occlusion (Pringle manoeuvre)

Hepatobiliary surgery and Nutrition 2020年第3期9卷 271-283页

作者： Lucinda Shen Zühre Uz Joanne Verheij Denise P.Veelo Yasin Ince Can Ince Thomas M.van Gulik department of Translational Physiology Amsterdam UMCLocation Academic Medical CenterUniversity of AmsterdamAmsterdamThe Netherlands department of Intensive Care Laboratory of Translational Intensive CareErasmus MCUniversity Medical CenterRotterdamThe Netherlands department of surgery Amsterdam UMCLocation Academic Medical CenterUniversity of AmsterdamAmsterdamThe Netherlands department of Pathology Amsterdam UMCLocation Academic Medical CenterUniversity of AmsterdamAmsterdamThe Netherlands department of Anesthesiology Amsterdam UMCLocation Academic Medical CenterUniversity of AmsterdamAmsterdamThe Netherlands

Background:Vascular inflow occlusion(VIO)during liver resections(Pringle manoeuvre)can be applied to reduce blood loss,however may at the same time,give rise to ischemia-reperfusion injury(IRI).The aim of this study was to assess the characteristics of hepatic microvascular perfusion during VIO in patients undergoing major liver ***:Assessment of hepatic microcirculation was performed using a handheld vital microscope(HVM)at the beginning of surgery,end of VIO(20 minutes)and during reperfusion after the termination of *** microcirculatory parameters assessed were:functional capillary density(FCD),microvascular flow index(MFI)and sinusoidal diameter(SinD).Results:A total of 15 patients underwent VIO;8 patients showed hepatic microvascular perfusion despite VIO(partial responders)and 7 patients showed complete cessation of hepatic microvascular perfusion(full responders).Functional microvascular parameters and blood flow levels were significantly higher in the partial responders when compared to the full responders during VIO(FCD:0.84±0.88 vs.0.00±0.00 mm/mm2,P<0.03,respectively,and MFI:0.69–0.22 vs.0.00±0.00,P<0.01,respectively).Conclusions:An interpatient heterogeneous response in hepatic microvascular blood flow was observed upon *** may explain why clinical strategies to protect the liver against IRI lacked consistency.

关键词： Liver perfusion microcirculation

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Familiarity, Knowledge and Practices of Healthcare Professionals Regarding the Pharmacovigilance of Biological Medicines in Lusaka, Zambia: A Multi-Facility Cross-Sectional Study

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Pharmacology & Pharmacy 2022年第7期13卷 230-251页

作者： Michelo Banda Katia Verhamme Webrod Mufwambi Steward Mudenda Billy Chabalenge Scott Kaba Matafwali Ronald Kampamba Mutati Christabel Nang’andu Hikaambo Martin Kampamba Lavina Prashar department of Pharmacy School of Health Sciences University of Zambia Lusaka Zambia department of Medical Informatics Erasmus MC Rotterdam Netherlands department of Bioanalysis Ghent University Ottergemsesteenweg Ghent Belgium department of Medicines Control Zambia Medicines Regulatory Authority Lusaka Zambia Clinical Research department Faculty of Infectious and Tropical Diseases London School of Hygiene & Tropical Medicine London UK department of Physiological Sciences School of Medicine University of Zambia Lusaka Zambia

Background: Pharmacovigilance of biological medicines is crucial because it ensures that medicines meet the World Health Organization (WHO) standards. In Zambia, there is little information on healthcare professionals’ familiarity, knowledge and practices on the pharmacovigilance of biological and biosimilar medicines. Therefore, this study investigated the familiarity, knowledge, and practices related to the pharmacovigilance (PV) of biological and biosimilar medicines at selected hospitals in Lusaka, Zambia. Methods: The study was an analytical questionnaire-based cross-sectional study conducted among healthcare professionals (HCPs) at the Adult hospital, Cancer Diseases hospital, Paediatrics hospital and Women and New Born Hospital in Lusaka. Data were collected over four weeks in May and June 2021 and subsequently analysed using IBM SPSS version 21. The statistical significance was set at a 95% confidence interval. Results: Of 245 participants, only 115 (48.9%) of the HCPs were familiar with biological medicines to a basic understanding. Regarding the term biosimilars, most of the HCPs (40.9%) never heard of this word. The mean score for knowledge regarding the PV considerations of biological medicines was 4.1 out of 8 questions. Most HCPs used non-proprietary names (44.2%) when prescribing, dispensing, or administering biological medicines. Additionally, more than half (57.3%) of HCPs did not record batch numbers when dispensing or administering biological medicines. Conclusion: Healthcare professionals were more familiar with the term biological medicines than biosimilars. Healthcare professionals generally scored poorly when their knowledge regarding the PV considerations of biological medicines was assessed. Thus, there is a need to provide adequate training and continuous professional development among healthcare professionals on the pharmacovigilance of biological and biosimilar medicines.

关键词： Pharmacovigilance Biological Medicines Biosimilars Brand Batch Zambia

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Bacterial inclusion bodies function as vehicles for dendritic cell-mediated T cell responses

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Cellular & Molecular Immunology 2020年第4期17卷 415-417页

作者： Sjoerd T.T.Schetters Wouter S.P.Jong Laura J.W.Kruijssen H.B.van den Berg van Saparoea Steef Engels Wendy W.J.Unger Diane Houben Joke M.M.den Haan Joen Luirink Yvette van Kooyk department of Molecular Cell Biology and Immunology Amsterdam UMCLocation VUmcAmsterdamThe Netherlands Abera Bioscience AB SolnaSweden Laboratory of Pediatrics Division of Pediatric Infectious Diseases and ImmunologyErasmus MC-Sophia Children’s HospitalRotterdamThe Netherlands department of Molecular Cell Biology Section Molecular MicrobiologyFaculty of ScienceVU UniversityAmsterdamThe Netherlands

Immunogenic antigens for vaccination are often created through the production of recombinant proteins using Escherichia coli.1 As a side product,aggregates called inclusion bodies(IBs)are formed,containing largely misfolded forms of the overexpressed recombinant protein.2 The effect of IBs on the immune system and whether they can be used as effective vaccine products remain *** non-native conformation of proteins upon accumulation in IBs abrogates their use as vaccines aimed at generating high-affinity antibodies.3 However,IBs exhibit unique properties,including mechanical and thermal stability due to their intrinsic particulate nature,biocompatibility,high antigenic content,low toxicity and relative resistance to *** characteristics make IBs attractive as an antigenic vaccine formulation for T cell responses to linear *** IBs can trigger adaptive cellular responses initiated via uptake by dendritic cells for presentation to T cells is unknown.

关键词： vaccine attractive initiated

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诊断囊性纤维化儿童支气管扩张和气道壁增厚:量化气道-动脉比值的目标

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国际医学放射学杂志 2018年第1期 113-114页

作者： W.Kuo M.de Bruijne J.Petersen K.Nasserinejad H.Ozturk Y.Chen 刘晓斌 department of Pediatric Pulmonology and Allergology Erasmus MC - Sophia Children’s Hospital

摘要目的通过量化囊性纤维化(CF)组和对照组病人的气道-动脉(AA)比值用于诊断支气管扩张和气道壁增厚(AWT)。方法回顾性收集CF组11例和对照组12例,对肺

关键词：气道壁支气管扩张囊性纤维化

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Association between serosal intestinal microcirculation and blood pressure during major abdominal surgery

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Journal of Intensive Medicine 2021年第1期1卷 59-64页

作者： Arthur LM Tavy Anton FJ de Bruin E Christiaan Boerma Can Ince Matthias P Hilty Peter G Noordzij Djamila Boerma Mat van Iterson department of Anesthesiology Intensive Care and Pain MedicineSt.Antonius HospitalNieuwegein 3435 CMthe Netherlands department of Intensive Care Medical Center LeeuwardenLeeuwarden 8934 ADthe Netherlands department of Intensive Care Medicine Erasmus MCUniversity Medical Center RotterdamRotterdam 3015 GDthe Netherlands Institute of Intensive Care Medicine University Hospital of ZurichZürich 8006Switzerland department of surgery St.Antonius HospitalNieuwegein 3435 CMthe Netherlands

Background:In clinical practice,blood pressure is used as a resuscitation goal on a daily basis,with the aim of maintaining adequate perfusion and oxygen delivery to target *** perfusion is often indicated as a key factor in the pathophysiology of anastomotic *** study was aimed at assessing the extent to which the microcirculation of the bowel coheres with blood pressure during abdominal ***:We performed a prospective and observational cohort *** patients undergoing abdominal surgery,the serosal microcirculation of either the small intestine or the colon was visualized using handheld vital mi-croscopy(HVM).From the acquired HVM image sequences,red blood cell velocity(RBCv)and total vessel density(TVD)were calculated using MicroTools and AVA software,*** association between microcircula-tory parameters and blood pressure was assessed using Pearson’s correlation *** considered a two-sided P-value ofsurgery,a total of 76 HVM images were *** RBCv was 335±96μm/s and the TVD was 13.7±3.4 mm/mm ^(2).Mean arterial pressure(MAP)was 71±12 mm Hg during microcirculatory *** was not correlated with RBCv(Pearson’s r=−0.049,P=0.800)or TVD(Pearson’s r=0.310,P=0.110).Conclusion:In 28 patients undergoing abdominal surgery,we found no association between serosal intestinal microcirculatory parameters and blood pressure.

关键词： Intestinal microcirculation Handheld vital microscopy Abdominal surgery Hemodynamic management

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基于算法的管理方案和常规管理方案在胰腺切除术后并发症早期识别和处理中的应用对比:一项荷兰国家级RCT研究

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肝胆外科杂志 2022年第4期30卷 245-245页

作者： Smits FJ Henry AC Besselink MG 马平川(译) 赵义军(校) department of surgery Regional Academic Cancer Centre Utrecht St Antonius Hospital Nieuwegein and University Medical Centre Utrecht Utrecht Netherlands department of surgery Cancer Centre Amsterdam Amsterdam UMC University of Amsterdam Amsterdam Netherlands department of surgery Erasmus MC Cancer Institute Rotterdam Netherlands department of Radiology Radboud University Medical Centre Nijmegen Netherlands department of Radiology Regional Academic Cancer Centre Utrecht St Antonius Hospital Nieuwegein and University Medical Centre Utrecht Utrecht Netherlands department of Radiology Cancer Centre Amsterdam Amsterdam UMC University of Amsterdam Amsterdam Netherlands department of Radiology Maastricht University Medical Centre Maastricht Netherlands department of Radiology and Nuclear Medicine Erasmus MC Cancer Institute Rotterdam Netherlands department of surgery Leiden University Medical Centre Leiden Netherlands department of surgery Jeroen Bosch Hospital Den Bosch Netherlands department of surgery Maastricht University Medical Centre Maastricht Netherlands

研究背景:超过20%的患者在大手术后发生围术期并发症,耗费了大量医疗资源和医保费用。因此,改善预后的重点应包括及时识别和并发症管理。胰腺切除术作为一种复杂手术,其并发症发生率和死亡率均较高。早期识别和处理并发症可以改善患者... 详细信息

研究背景:超过20%的患者在大手术后发生围术期并发症,耗费了大量医疗资源和医保费用。因此,改善预后的重点应包括及时识别和并发症管理。胰腺切除术作为一种复杂手术,其并发症发生率和死亡率均较高。早期识别和处理并发症可以改善患者预后。研究方法:本研究是一项开放标签、全国性、阶梯楔形聚类随机试验,纳入所有接受胰腺切除术的患者,无针对中心或患者的排除标准。所有17家进行胰腺手术的中心均被随机分配到常规术后管理(对照组)和根据多模式、多学科算法早期识别和微创处理术后并发症组(干预组)。本研究开发了一个智能手机软件,该软件结合了该算法包括临床和生化标志物的日常评估,确定何时进行腹部CT、穿刺引流、抗感染和拔除腹部引流管。研究终点为需要侵入性干预的出血、器官衰竭以及术后90天内死亡。算法开发的源数据来自既往研究报道和国家数据库。

关键词：胰腺切除术器官衰竭生化标志物医保费用胰腺手术医疗资源穿刺引流早期识别

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通过微观模拟对机械瓣膜与生物瓣膜主动脉瓣膜置换术后效果的比较研究

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世界核心医学期刊文摘（心脏病学分册） 2005年第2期1卷 38-39页

作者： Puvimanasinghe J.P.A. Takkenberg J.J.M. Edwards M.B. 张明娟 department of Cardiothoracic surgery Erasmus MC R otterdam Netherlands Dr.

Background: Mechanical valves and bioprostheses are widely used for aortic val ve replacement. Though previous randomised studies indicate that there is no imp ortant difference in outcome after implantation with either type of valve, knowl edge of outcomes after aortic valve replacement is incomplete. Objective: To pre dict age and sex specific outcomes of patients after aortic valve replacement wi th bileaflet mechanical valves and stented porcine bioprostheses, and to provide evidence based support for the choice of prosthesis. Methods: Meta analysis of published results of primary aortic valve replacement with bileaflet mechanical prostheses(nine reports, 4274 patients, and 25 726 patient years) and stented porcine bioprostheses (13 reports, 9007 patients, and 54 151 patient years) was used to estimate the annual risks of postoperative valve related events and th eir outcomes. These estimates were entered into a microsimulation model, which w as employed to calculate age and sex specific outcomes after aortic valve replac ement. Results: Life expectancy(LE) and event free life expectancy(EFLE) for a 65 year old man after implantation with a mechanical valve or a bioprosthesis we re 10.4 and 10.7 years and 7.7 and 8.4 years, respectively. The lifetime risk of at least one valve related event for a mechanical valve was 48%, and for a bio prosthesis, 44%. For LE and EFLE, the age crossover point between the two valve types was 59 and 60 years, respectively. Conclusions: Meta analysis based micr osimulation provides insight into the long term outcome after aortic valve repla cement and suggests that the currently recommended age threshold for implanting a bioprosthesis could be lowered further.

关键词：主动脉瓣膜机械瓣膜生物瓣膜微观模拟置换术双叶研究报告随机研究荟萃分析特异性

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The hypoxia-inducible factor-1α activates ectopic production of fibroblast growth factor 23 in tumor-induced osteomalacia

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Bone Research 2016年第2期4卷 85-90页

作者： Qian Zhang Michele Doucet Ryan E Tomlinson Xiaobin Han L Darryl Quarles Michael T Collins Thomas L Clemens department of orthopaedic surgery Johns Hopkins University Baltimore MD USA department of Medicine University of Tennessee Health Science Center Memphis TN USA Skeletal Clinical Studies Unit craniofacial and Skeletal Diseases Branch National Institutes of HealthBethesda MD USA Baltimore Veterans Administration Medical Center Baltimore MD USA

Tumor-induced osteomalacia （TIO） is a rare paraneoplastic syndrome in which ectopic production of fibroblast growth factor 23 （FGF23） by non-malignant mesenchymal tumors causes phosphate wasting and bone fractures. Recent studies have implicated the hypoxia-inducible factor-la （HIF-la） in other phosphate wasting disorders caused by elevated FGF23, including X-linked hypophosphatemic rickets and autosomal dominant hypophosphatemia. Here we provide evidence that HIF-la mediates aberrant FGF23 in TIO by transcriptionally activating its promoter. Immunohistochemical studies in phosphaturic mesenchymal tumors resected from patients with documented TIO showed that HIF-la and FGF23 were co-localized in spindle- shaped cells adjacent to blood vessels. Cultured tumor tissue produced high levels of intact FGF23 and demonstrated increased expression of HIF-la protein. Transfection of mc3T3-E1 and Saos-2 cells with a HIF-la expression construct induced the activity of a FGF23 reporter construct. Prior treatment of tumor organ cultures with HIF-la inhibitors decreased HIF-la and FGF23 protein accumulation and inhibited HIF-la-induced luciferase reporter activity in transfected cells. Chromatin immunoprecipitation assays confirmed binding to a HIF-la consensus sequence within the proximal FGF23 promoter, which was eliminated by treatment with a HIF-la inhibitor. These results show for the first time that HIF-la is a direct transcriptional activator of FGF23 and suggest that upregulation of HIF-la activity in TIO contributes to the aberrant FGF23 production in these patients.

关键词： The hypoxia-inducible factor-1 activates ectopic production of fibroblast growth factor 23 in tumor-induced osteomalacia HIF

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Hepatitis E virus infection induces mitochondrial fusion to facilitate viral replication

Hepatitis E virus infection induces mitochondrial fusion to ...

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第十五届中国体视学与图像分析学术会议

作者： Yijin Wang Qiuwei Pan Jingmin Zhao department of Pathology and Hepatology Beijing 302 Hospital department of Gastroenterology and Hepatology Erasmus MC-University Medical Center

Competing Interests:The authors have declared that no competing interests ***:The liver contains abundant copies of mitochondria,which play important roles in physiology and *** have been reported to disrupt mitochondrial machinery by manipulating their dynamics including the processes of fusion and fission to facilitate viral *** study

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Phase Ⅱ study of docetaxel,cisplatin and capecitabine as preoperative chemotherapy in resectable gastric cancer

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World Journal of Gastrointestinal surgery 2016年第10期8卷 706-712页

作者： Anneriet E Dassen Nienke Bernards Valery EPP Lemmens Yes AJ van de Wouw Koop Bosscha Geert-Jan Creemers Hans JFM Pruijt department of Gastro-intestinal surgery and Surgical Oncology Jeroen Bosch Hospital department of Oncology Catharina Hospital Comprehensive Cancer South (IKZ) Eindhoven Cancer Registry department of Public Health Erasmus MC University department of Oncology Vie Curi Hospital department of Oncology Jeroen Bosch Hospital

AIM To investigate the feasibility of preoperative docetaxel,cisplatin and capecitabine(DCC) in patients with resectable gastric *** Patients with resectable gastric cancer fulfilling the inclusion criteria,were treated with 4 cycles of docetaxel(60 mg/m2),cisplatin(60 mg/m2) and capecitabine(1.875 mg/m2 orally on day 1-14,two daily doses) repeated every three weeks,followed by *** end point was the feasibility and toxicity/safety profile of DCC,secondary endpoints were pathological complete resection rate and pathological complete response(p CR) *** All of the patients(51) were assessable for the feasibility and safety of the *** entire preoperative regimen was completed by 68.6% of the *** Ⅲ/Ⅳ febrile neutropenia occurred in 10% of all *** patients died due to treatment related toxicity(5.9%),one of them(also) because of refusing further treatment for *** the 45 patients who were evaluable for secondary endpoints,four developed metastatic disease and 76.5% received a curative *** 3 patients a p CR was seen(5.9%),two patients underwent a R1 resection(3.9%).CONCLUSION Four courses of DCC as a preoperative regimen for patients with primarily resectable gastric cancer is highly *** high occurrence of febrile neutropenia is of *** decrease the occurrence of febrile neutropenia the prophylactic use of granulocyte colonystimulating factor(G-CSF) should be explored.A curative resection rate of 76.5% is *** use of DCC without G-CSF support as preoperative regimen in resectable gastric cancer is debatable.

关键词： Gastric cancer Preoperative chemotherapy Docetaxel Capecitabine

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