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脑海绵状血管畸形临床诊疗指南概要：血管瘤联盟科学咨询委员会临床专家组基于系统文献评价的共识推荐

国际脑血管病杂志 2017年第7期25卷 577-591页

作者： Amy Akers Rustam Al-Shahi Salman Issam A. Awad Kristen Dahlem kelly flemming Blaine Hart Helen Kim Ignacio Jusue-Torres Douglas Kondziolka Cornelia Lee Leslie Morrison Daniele Rigamonti Tania Rebeiz Elisabeth Toumier-Lasserve Darrel Waggoner Kevin Whitehead 鄂同舟雷宇倪伟顾宇翔 Angioma Alliance Norfolk Virginia Centre for Clinical Brain Sciences University of Edinburgh Edinburgh United Kingdom Neurovascular Surgery Program Section of Neurosurgery" University of Chicago Medicine" and Biological Sciences Chicago Illinois Department of Neurology Mayo Clinic Rochester Minnesota Department of Radiology University of New Mexico Albuquerque New Mexico Department of Anesthesia and Perioperative Care Department of Epidemiology and Biostatistics University of California San Francisco San Francisco California Department of Ncurosurgery Johns Hopkins Medicine Baltimore Maryland Departments of Neurosurgery and Radiation Oncology NYU Langone Medical Center New York City New York Departments of Neurology and Pediatrics University of New Mexico Albuquerque New Mexico Department of Genetics INSERM UMR 1161 Pads France Department of Human Genetics and Pediatrics University of Chicago Medicine and Biological Sciences Chicago Illinois Department of Cardiovascular Medicine University of Utah Salt Lake City Utah 复旦大学附属华山医院神经外科上海200040

背景尽管脑海绵状血管畸形（cerebral cavernous malformation, CCM）的相关研究文献已相当丰富，但在诊断和治疗策略方面仍存在着争议。目的制订CCM诊疗指南。方法作为代表CCM患者和研究的患者支持团体，血管瘤联盟（***）召集了一个包... 详细信息

背景尽管脑海绵状血管畸形（cerebral cavernous malformation, CCM）的相关研究文献已相当丰富，但在诊断和治疗策略方面仍存在着争议。目的制订CCM诊疗指南。方法作为代表CCM患者和研究的患者支持团体，血管瘤联盟（***）召集了一个包括CCM临床专家在内的多学科写作组来帮助总结现有的CCM临床诊疗相关文献，重点关注5个主题：（1）流行病学和自然病程；（2）遗传检测和咨询；（3）诊断标准和影像学标准；（4）神经外科注意事项；（5）神经内科注意事项。写作组根据预定方案进行了文献回顾和证据评价，最终制定推荐意见，并且确立了共识、争议和知识空白。结果根据方法学标准从1983年1月1日至2014年9月31日期间公开发表的1 270篇文献中筛选出98篇，并确定了另外38篇近期或相关的文献。各主题作者利用这些文献总结了现有知识并形成了23项共识诊疗推荐，同时根据美国心脏协会/美国卒中协会标准进行了推荐强度（效应量）和证据水平（确定性估计）评级。其中，尚无A级证据（因为缺乏随机对照试验），B级证据11项（48%），C级证据12项（52%）；Ⅰ级推荐8项（35%），Ⅱ级推荐10项（43%），Ⅲ级推荐5项（22%）。结论现有证据支持对CCM诊疗的推荐，但这些证据的级别和推荐强度普遍较低，因此需要进一步研究来帮助进行更好的临床实践并更新这些推荐。完整的推荐文档包括引用文献的纳入标准、关于各项推荐更详尽的评判标准以及各种争议和知识空白的总结，同样通过了同行评议并可在线获取（***/CCMGuidelines）。

关键词：海绵状血管瘤血管畸形指南推荐

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Viscosity of food boluses affects the axial force in the esophagus

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World Journal of Gastroenterology 2011年第15期17卷 1982-1988页

作者： flemming Gravesen Niall Behan Asbjorn Drewes Hans Gregersen Mech-Sense Aalborg Hospital Hobrovej 9000 Aalborg Denmark Vysera Biomedical Ltd. BMR House Parkmore Business Park West Galway Ireland Sino-Danish Center for Education and Research Niels Jensens Vej 28000 Aarhus Denmark

AIM: To study the effect of viscosity on axial force in the esophagus during primary peristalsis using a newly validated impedance-based axial force recording technique. METHODS: A probe able to simultaneously measure both axial force and manometry was positioned above the lower esophageal sphincter. Potable tap water and three thickened fluids were used to create boluses of different viscosities. Water has a viscosity of 1 mPa·s. The three thickened fluids were made with different concentrations of Clinutren Instant thickener. The viscous fluids were in appearance comparable to pudding (2 kPa·s), yogurt (6 kPa·s) and slush ice (10 kPa·s). Six healthy volunteers swallowed 5 and 10 mL of boluses multiple times. RESULTS: The pressure amplitude did not increase with the bolus viscosity nor with the bolus volume whereas the axial force increased marginally with bolus volume (0.1 > P > 0.05). Both techniques showed that contraction duration increased with bolus viscosity (P < 0.01). Association was found between axial force and pressure but the association became weaker withincreasing viscosity. The pressure amplitude did not increase with the viscosity or bolus volume whereas the axial force increased marginally with the bolus size. CONCLUSION: This indicates a discrepancy between the physiological functions that can be recorded with axial force measurements and pressure measurements.

关键词： Axial force Manometry Esophagus Primary peristalsis Viscosity

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Recent Progress in Emerging Two‑Dimensional Transition Metal Carbides

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Nano-Micro Letters 2021年第11期13卷 375-408页

作者： Tianchen Qin Zegao Wang Yuqing Wang flemming Besenbacher Michal Otyepka Mingdong Dong College of Materials Science and Engineering Sichuan UniversityChengdu 610065People’s Republic of China Interdisciplinary Nanoscience Center Aarhus University8000 AarhusDenmark Regional Centre of Advanced Technologies and Materials Department of Physical ChemistryFaculty of SciencePalacky University77146 OlomoucCzech Republic

As a new member in two-dimensional materials family,transition metal carbides(TMCs)have many excellent properties,such as chemical stability,in-plane anisotropy,high conductivity and flexibility,and remarkable energy conversation efficiency,which predispose them for promising applications as transparent electrode,flexible electronics,broadband photodetectors and battery ***,up to now,their device applications are in the early stage,especially because their controllable synthesis is still a great *** review systematically summarized the state-of-the-art research in this rapidly developing field with particular focus on structure,property,synthesis and applicability of ***,the current challenges and future perspectives are outlined for the application of 2D TMCs.

关键词： Two-dimensional transition metal carbides Phase diagram Superconductivity Energy conversation and storage Largescale synthesis

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Pharmacological approach to acute pancreatitis

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World Journal of Gastroenterology 2008年第19期14卷 2968-2976页

作者： Ulrich Christian Bang Synne Semb Camilla Nφjgaard flemming Bendtsen Department of Gastroenterology Hvidovre Hospital

The aim of the present review is to summarize the current knowledge regarding pharmacological prevention and treatment of acute pancreatitis (AP) based on experimental animal models and clinical trials. Somatostatin (SS) and octreotide inhibit the exocrine production of pancreatic enzymes and may be useful as prophylaxis against Post Endoscopic retrograde cholangiopancreatography Pancreatitis (PEP). The protease inhibitor Gabexate mesilate (GM) is used routinely as treatment to AP in some countries, but randomized clinical trials and a meta-analysis do not support this practice. Nitroglycerin (NGL) is a nitrogen oxide (NO) donor, which relaxes the sphincter of Oddi. Studies show conflicting results when applied prior to ERCP and a large multicenter randomized study is warranted. Steroids administered as prophylaxis against PEP has been validated without effect in several randomized trials. The non-steroidal anti-inflammatory drugs (NSAID) indomethacin and diclofenac have in randomized studies showed potential as prophylaxis against PEP. Interleukin 10 (IL-10) is a cytokine with anti-inflammatory properties but two trials testing IL-10 as prophylaxis to PEP have returned conflicting results. Antibodies against tumor necrosis factor-alpha (TNF-α) have a potential as rescue therapy but no clinical trials are currently being conducted. The antibiotics beta- lactams and quinolones reduce mortality when necrosis is present in pancreas and may also reduce incidence of infected necrosis. Evidence based pharmacological treatment of AP is limited and studies on the effect of potent anti-inflammatory drugs are warranted.

关键词： Acute pancreatitis Diclofenac Gabexate Indomethacin Interleukin-10 Necrotizing pancreatitis Nitrogen oxides Octreotide Protease inhibitors Somatostatin

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Extrahepatic complications to cirrhosis and portal hypertension: Haemodynamic and homeostatic aspects

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World Journal of Gastroenterology 2014年第42期20卷 15499-15517页

作者： S?ren M?ller Jens H Henriksen flemming Bendtsen Department of Clinical Physiology and Nuclear Medicine Center for Functional and Diagnostic Imaging and Research Copenhagen University Hospital University of Copenhagen Gastro Unit Medical Division Hvidovre Hospital Hvidovre Hospital Faculty of Health Sciences University of Copenhagen

In addition to complications relating to the liver, patients with cirrhosis and portal hypertension develop extrahepatic functional disturbances of multiple organ systems. This can be considered a multiple organ failure that involves the heart, lungs, kidneys, the immune systems, and other organ systems. Progressive fibrosis of the liver and subsequent metabolic impairment leads to a systemic and splanchnic arteriolar vasodilatation. This affects both the haemodynamic and functional homeostasis of many organs and largely determines the course of the disease. With the progression of the disease, the circulation becomes hyperdynamic with cardiac, pulmonary as well as renal consequences for dysfunction and reduced survival. Infections and a changed cardiac function known as cirrhotic cardiomyopathy may be involved in further aggravation of other complications such as renal failure precipitatingthe hepatorenal *** with end-stage liver disease and related complications as for example the hepatopulmonary syndrome can only radically be treated by liver *** a bridge to this treatment,knowledge on the mechanisms of the pathophysiology of complications is essential for the choice of vasoactive drugs,antibiotics,drugs with specific effects on fibrogenesis and inflammation,and drugs that target specific receptors.

关键词： Fibrogenesis Splanchnic haemodynamics Inflammation Bacterial translocation Infections Systemic circulation Cirrhotic cardiomyopathy Hepatopulmonary syndrome Portopulmonary hypertension Hepatorenal syndrome Ascites

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Persistent severe hypomagnesemia caused by proton pump inhibitor resolved after laparoscopic fundoplication

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World Journal of Gastroenterology 2017年第37期23卷 6907-6910页

作者： Synne Semb Frederik Helgstrand flemming Hjorne Peter Bytzer Department of Gastroenterology Zealand University Hospital Department of Surgery Zealand University Hospital Department of Clinical Medicine University of Copenhagen

Magnesium deficiency can cause a variety of symptoms, including potentially life-threatening complications such as seizures, cardiac arrhythmias and secondary electrolyte disturbances. Hypomagnesemia can be a serious adverse effect to proton pump inhibitor(PPI) therapy, which is worrying due to the widespread use of PPIs. Current evidence suggest that the mechanism of PPI induced hypomagnesemia is impaired intestinal magnesium absorption. In this report, we present the case of a long-term PPI user with persistent hypomagnesemia with severe symptoms at presentation. He was unable to stop PPI treatment because of severe reflux symptoms, and was dependent on weekly intravenous magnesium infusions, until his magnesium levels finally normalized without the need for supplementation after a successful laparoscopic fundoplication.

关键词： Hypomagnesemia Proton pump inhibitor Gastroesophageal reflux disease Drug adverse effect Laparoscopic fundoplication

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Safety and efficacy of Profermin~to induce remission in ulcerative colitis

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World Journal of Gastroenterology 2012年第15期18卷 1773-1780页

作者： Aleksander Krag Hans Israelsen Bjrn von Ryberg Klaus K Andersen flemming Bendtsen Gastrounit Medical Devision 360Copenhagen University Hospital Hvidovre Faculty of Health Sciences Copenhagen UniversityDK-2650 HvidovreDenmark Nordisk Rebalance A/S M.D.Madsensvej 14-16DK-3450 AllerdDenmark Statistics Section Informatics and Mathematical ModellingTechnical University of DenmarkDK-2800 LyngbyDenmark

AIM:To test the efficacy and safety of Profermin in inducing remission in patients with active ulcerative colitis(UC).METHODS:The study included 39 patients with mild to moderate UC defined as a Simple Clinical Colitis Activity Index(SCCAI)>4 and<12(median:7.5),who were treated open-label with Profermintwice daily for 24 *** SCCAI was reported observer blinded via the ***:In an intention to treat(ITT)analysis,the mean reduction in SCCAI score was 56.5%.Of the 39 patients,24(62%)reached the primary endpoint,which was proportion of patients with≥50%reduction in *** secondary endpoint,the proportion of patients in remission defined as SCCAI≤2.5,was in ITT analysis reached in 18 of the 39 patients(46%).In a repeated-measure regression analysis,the estimated mean reduction in score was 5.0 points(95%CI:4.1-5.9,P<0.001)and the estimated mean time taken to obtain half the reduction in score was 28 d(95%CI:26-30).There were no serious adverse events(AEs)or withdrawals due to *** was generally well ***:Profermin is safe and may be effective in inducing remission of active UC.

关键词： Ulcerative colitis Diet Probiotic Profermin Inflammatory bowel disease Dietary management Medical foods

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Systematic review of the prevalence and development of osteoporosis or low bone mineral density and its risk factors in patients with inflammatory bowel disease

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World Journal of Gastroenterology 2020年第35期26卷 5362-5374页

作者： Sofia Kärnsund Bobby Lo flemming Bendtsen Jakob Holm Johan Burisch Gastrounit Medical DivisionCopenhagen University Hospital HvidovreHvidovre 2650Denmark Department of Endocrinology Copenhagen University Hospital HerlevHerlev 4600Denmark

BACKGROUND The inflammatory bowel diseases(IBD),Crohn’s disease(CD)and ulcerative colitis(UC)are chronic,immune-mediated disorders of the digestive *** is considered to be a risk factor for developing osteoporosis;however current literature on this matter is *** To assess prevalence and development of osteoporosis and low bone mineral density(BMD),and its risk factors,in IBD *** Systematic review of population-based *** were identified by electronic(January 2018)and manual searches(May 2018).Databases searched included EMBASE and PubMed and abstracts from 2014-2018 presented at the United European Gastroenterology Week,the European Crohn’s and Colitis Organisation congress,and Digestive Disease Week were *** were eligible for inclusion if they investigated either the prevalence of osteoporosis or osteopenia and/or risk factors for osteoporosis or low BMD in IBD *** on children under the age of 18 were *** population-based studies were *** risk factors for osteoporosis and low BMD investigated in any included article were *** quality and the possibility of bias were analysed using the Newcastle-Ottawa *** Twelve studies including 3661 IBD patients and 12789 healthy controls were *** of osteoporosis varied between 4%-9%in studies including both CD and UC patients;2%-9% in studies including UC patients, and 7%-15% instudies including CD patients. Among healthy controls, prevalence ofosteoporosis was 3% and 10% in two studies. CD diagnosis, lower body massindex (BMI), and lower body weight were risk factors associated withosteoporosis or low BMD. Findings regarding gender showed inconsistent *** patients had an increased risk for osteoporosis or low BMD over time, whileUC patients did not. Increased age was associated with decreased BMD, and therewas a positive association between weight and BMI and BMD over time. Greatheterogeneity was

关键词： Inflammatory bowel disease Osteoporosis Systematic review Epidemiology Bone mineral density

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Axial force measurement for esophageal function testing

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World Journal of Gastroenterology 2009年第2期15卷 139-143页

作者： flemming H Gravesen Peter Funch-Jensen Hans Gregersen Asbjφrn Mohr Drewes Mech-Sense Department of Gastroenterology Aalborg Hospital Aalborg Denmark Center for Sensory-Motor Interaction (SMI) Department of Health Science and Technology Aalborg University DK-9000 Aalborg Denmark Department of Surgical Gastroenterology L rhus University Hospital rhus Denmark

The esophagus serves to transport food and fluid from the pharynx to the stomach. Manometry has been the "golden standard" for the diagnosis of esophageal motility diseases for many decades. Hence, esophageal function is normally evaluated by means of manometry even though it reflects the squeeze force (force in radial direction) whereas the bolus moves along the length of esophagus in a distal direction. Force measurements in the longitudinal (axial) direction provide a more direct measure of esophageal transport function. The technique used to record axial force has developed from external force transducers over in-vivo strain gauges of various sizes to electrical impedance based measurements. The amplitude and duration of the axial force has been shown to be as reliable as manometry. Normal, as well as abnormal, manometric recordings occur with normal bolus transit, which have been documented using imaging modalities such as radiography and scintigraphy. This inconsistency using manometry has also been documented by axial force recordings. This underlines the lack of information when diagnostics are based on manometry alone. Increasing the volume of a bag mounted on a probe with combined axial force and manometry recordings showed that axial force amplitude increased by 130% in contrast to an increase of 30% using manometry. Using axial force in combination with manometry provides a more complete picture of esophageal motility, and the current paper outlines the advantages of using this method.

关键词： Axial force Traction force Manometry Motility Peristalsis Esophageal function

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Serum-induced degradation of 3D DNA box origami observed with high-speed atomic force microscopy

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Nano Research 2015年第7期8卷 2170-2178页

作者： Zaixing Jiang Shuai Zhang Chuanxu Yang Jorgen Kjems Yudong Huang flemming Besenbacher Mingdong Dong Department of Polymer Science and Technology School of Chemical Engineering and Technology Harbin Institute of Technology Harbin 150001 China Interdisciplinary Nanoscience Center (iNANO) Aarhus University DK-8000 Aarhus C Denmark These authors contributed equally to this study.

3D DNA origami holds tremendous potential for the encapsulation and selective release of therapeutic drugs. Observations of the real-time performance of these structures in physiological environments will contribute to the development of future applications. We investigated the degradation kinetics of 3D DNA box origami in serum by using high-speed atomic force microscope optimized for imaging 3D DNA origami in real time. The time resolution allowed to characterize the stages of serum effects on individual 3D DNA boxes origami with nanometer resolution. Our results indicate that the digestion process is a combination of rapid collapse and slow degradation phases. Damage to box origami occurs mainly in the collapse phase. Thus, the structural stability of 3D DNA box origami should be improved, especially in the collapse phase, before these structures are used in clinical applications.

关键词： 3D DNAbox origami,high-speed AFM.stability,serum,kinefics

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