Most frequent procedures according to gender [1].
\\n\\n
\\n"}]',published:!0,mainMedia:{caption:"Milestone",originalUrl:"/media/original/124"}},components:[{type:"htmlEditorComponent",content:'
Barely three months into the new year and we are happy to announce a monumental milestone reached - 150 million downloads.
\n\nThis achievement solidifies IntechOpen’s place as a pioneer in Open Access publishing and the home to some of the most relevant scientific research available through Open Access.
\n\nWe are so proud to have worked with so many bright minds throughout the years who have helped us spread knowledge through the power of Open Access and we look forward to continuing to support some of the greatest thinkers of our day.
\n\nThank you for making IntechOpen your place of learning, sharing, and discovery, and here’s to 150 million more!
\n\n\n\n\n'}],latestNews:[{slug:"intechopen-supports-asapbio-s-new-initiative-publish-your-reviews-20220729",title:"IntechOpen Supports ASAPbio’s New Initiative Publish Your Reviews"},{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"}]},book:{item:{type:"book",id:"10677",leadTitle:null,fullTitle:"Advanced Topics of Topology",title:"Advanced Topics of Topology",subtitle:null,reviewType:"peer-reviewed",abstract:"Topology is an area of mathematics that establishes relations and transformations between spaces with a certain structure depending on their position and considering the structure of the ambient space where these relations exist. This book discusses various concepts and theories of topology, including diffeomorphisms, immersions, Hausdorff spaces, cobordisms, homotopy theory, symplectic manifolds, topology of quantum field theory, algebraic varieties, dimension theory, Koszul complexes, continuum theory, and metrizability, among others.",isbn:"978-1-80355-094-7",printIsbn:"978-1-80355-093-0",pdfIsbn:"978-1-80355-095-4",doi:null,price:119,priceEur:129,priceUsd:155,slug:"advanced-topics-of-topology",numberOfPages:136,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"bf964c52f9e653fac20a7fcab58070e5",bookSignature:"Francisco Bulnes",publishedDate:"July 27th 2022",coverURL:"https://cdn.intechopen.com/books/images_new/10677.jpg",numberOfDownloads:545,numberOfWosCitations:0,numberOfCrossrefCitations:1,numberOfCrossrefCitationsByBook:null,numberOfDimensionsCitations:1,numberOfDimensionsCitationsByBook:null,hasAltmetrics:0,numberOfTotalCitations:2,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"June 25th 2021",dateEndSecondStepPublish:"September 14th 2021",dateEndThirdStepPublish:"November 13th 2021",dateEndFourthStepPublish:"February 1st 2022",dateEndFifthStepPublish:"April 2nd 2022",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"92918",title:"Dr.",name:"Francisco",middleName:null,surname:"Bulnes",slug:"francisco-bulnes",fullName:"Francisco Bulnes",profilePictureURL:"https://mts.intechopen.com/storage/users/92918/images/system/92918.png",biography:"Dr. Francisco Bulnes, Ph.D., is IINAMEI Director, Mathematics Research Centre, Mexico. He is a member of various international committees of science and serves as a reviewer and editor for British and American journals of mathematics and physics. He is head of the Research Department, GI-TESCHA. He has published more than 100 papers and several books in mathematics and physics. Dr. Bulnes has many theories, theorems, and math objects to his credit. He has received various honors and awards from universities as well as governmental and non-governmental organizations. He received the Doctor Honoris Causa in Education Philosophy and is a Peace Ambassador for ODAEE in Frankfurt, Germany. He is also a distinguished member of the Czech Republic Mathematics Society (JCFM). He obtained two post-doctorates in Mathematics in Cuba and Russia. His research interests include electronics, microelectronics, and spintronics.",institutionString:"Investigación Internacional Avanzada en Matemáticas e Ingeniería (IINAMEI)",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"14",totalChapterViews:"0",totalEditedBooks:"7",institution:null}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"165",title:"Geometry & Topology",slug:"geometry-and-topology"}],chapters:[{id:"80411",title:"Introductory Chapter: The Topology from Classic Studies until Its Last Frontiers",doi:"10.5772/intechopen.102527",slug:"introductory-chapter-the-topology-from-classic-studies-until-its-last-frontiers",totalDownloads:9,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:null,signatures:"Francisco Bulnes",downloadPdfUrl:"/chapter/pdf-download/80411",previewPdfUrl:"/chapter/pdf-preview/80411",authors:[{id:"92918",title:"Dr.",name:"Francisco",surname:"Bulnes",slug:"francisco-bulnes",fullName:"Francisco Bulnes"}],corrections:null},{id:"78241",title:"More Functions Associated with Neutrosophic gsα*- Closed Sets in Neutrosophic Topological Spaces",doi:"10.5772/intechopen.99464",slug:"more-functions-associated-with-neutrosophic-gs-closed-sets-in-neutrosophic-topological-spaces",totalDownloads:116,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"The concept of neutrosophic continuous function was very first introduced by A.A. Salama et al. The main aim of this paper is to introduce a new concept of Neutrosophic continuous function namely Strongly Neutrosophic gsα* - continuous functions, Perfectly Neutrosophic gsα* - continuous functions and Totally Neutrosophic gsα* - continuous functions in Neutrosophic topological spaces. These concepts are derived from strongly generalized neutrosophic continuous function and perfectly generalized neutrosophic continuous function. Several interesting properties and characterizations are derived and compared with already existing neutrosophic functions.",signatures:"P. Anbarasi Rodrigo and S. Maheswari",downloadPdfUrl:"/chapter/pdf-download/78241",previewPdfUrl:"/chapter/pdf-preview/78241",authors:[{id:"426315",title:"Dr.",name:"P. Anbarasi",surname:"Rodrigo",slug:"p.-anbarasi-rodrigo",fullName:"P. Anbarasi Rodrigo"},{id:"426558",title:"Ms.",name:"S.",surname:"Maheswari",slug:"s.-maheswari",fullName:"S. Maheswari"}],corrections:null},{id:"80455",title:"4-Dimensional Canards with Brownian Motion",doi:"10.5772/intechopen.102151",slug:"4-dimensional-canards-with-brownian-motion",totalDownloads:55,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Generally speaking, it is impossible to analyze slow-fast system with Brownian motion. If it becomes possible to do using a new approach, we can evaluate the rigidity of the original system. What kind of the behavior of such a system we have? Using non-standard analysis, on a“hyper finite time line” by Anderson, the Brownian motions are described by step functions. Then, the original differential equations are described by the difference equations due to using non-standard analysis. When constructing the difference equations, the corresponding measure is extended topologically. Because the interval of the difference is according to the hyper finite time line, the topological space is well defined. In this paper, we propose a two-region economic model with Brownian motions. This concrete example gives us new results.",signatures:"Shuya Kanagawa and Kiyoyuki Tchizawa",downloadPdfUrl:"/chapter/pdf-download/80455",previewPdfUrl:"/chapter/pdf-preview/80455",authors:[{id:"427472",title:"Prof.",name:"Shuya",surname:"Kanagawa",slug:"shuya-kanagawa",fullName:"Shuya Kanagawa"},{id:"427473",title:"Dr.",name:"Kiyoyuki",surname:"Tchizawa",slug:"kiyoyuki-tchizawa",fullName:"Kiyoyuki Tchizawa"}],corrections:null},{id:"79299",title:"The Topology of the Configuration Space of a Mathematical Model for Cycloalkenes",doi:"10.5772/intechopen.100723",slug:"the-topology-of-the-configuration-space-of-a-mathematical-model-for-cycloalkenes",totalDownloads:123,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"As a mathematical model for cycloalkenes, we consider equilateral polygons whose interior angles are the same except for those of the both ends of the specified edge. We study the configuration space of such polygons. It is known that for some case, the space is homeomorphic to a sphere. The purpose of this chapter is threefold: First, using the h-cobordism theorem, we prove that the above homeomorphism is in fact a diffeomorphism. Second, we study the best possible condition for the space to be a sphere. At present, only a sphere appears as a topological type of the space. Then our third purpose is to show the case when a closed surface of positive genus appears as a topological type.",signatures:"Yasuhiko Kamiyama",downloadPdfUrl:"/chapter/pdf-download/79299",previewPdfUrl:"/chapter/pdf-preview/79299",authors:[{id:"327075",title:"Prof.",name:"Yasuhiko",surname:"Kamiyama",slug:"yasuhiko-kamiyama",fullName:"Yasuhiko Kamiyama"}],corrections:null},{id:"82378",title:"Covers and Properties of Families of Real Functions",doi:"10.5772/intechopen.100555",slug:"covers-and-properties-of-families-of-real-functions",totalDownloads:16,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"We present results on the relationships of the covering property GΦΨ for Φ,Ψ∈OΛΩΓ and G∈S1SfinUfin of a topological space and the selection property GΦ0Ψ0 of the corresponding family of real functions. The result already published are presented without a proof, however with a citation of the corresponding paper. We present a general Theorem that covers almost all the result of this kind. Some results about hereditary properties are enclosed. We also present Scheepers Diagram of considered covering properties for uncountable covers.",signatures:"Lev Bukovský",downloadPdfUrl:"/chapter/pdf-download/82378",previewPdfUrl:"/chapter/pdf-preview/82378",authors:[{id:"427352",title:"Emeritus Prof.",name:"Lev",surname:"Bukovský",slug:"lev-bukovsky",fullName:"Lev Bukovský"}],corrections:null},{id:"80019",title:"Vertex Decomposability of Path Complexes and Stanley’s Conjectures",doi:"10.5772/intechopen.101083",slug:"vertex-decomposability-of-path-complexes-and-stanley-s-conjectures",totalDownloads:55,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Monomials are the link between commutative algebra and combinatorics. With a simplicial complex Δ, one can associate two square-free monomial ideals: the Stanley-Reisner ideal IΔ whose generators correspond to the non-face of Δ, or the facet ideal I(Δ) that is a generalization of edge ideals of graphs and whose generators correspond to the facets of Δ. The facet ideal of a simplicial complex was first introduced by Faridi in 2002. Let G be a simple graph. The edge ideal I(G) of a graph G was first considered by R. Villarreal in 1990. He studied algebraic properties of I(G) using a combinatorial language of G. In combinatorial commutative algebra, one can attach a monomial ideal to a combinatorial object. Then, algebraic properties of this ideal are studied using combinatorial properties of combinatorial object. One of interesting problems in combinatorial commutative algebra is the Stanley’s conjectures. The Stanley’s conjectures are studied by many researchers. Let R be a Nn-graded ring and M a Zn-graded R-module. Then, Stanley conjectured that depthM≤sdepthM. He also conjectured that each Cohen-Macaulay simplicial complex is partition-able. In this chapter, we study the relation between vertex decomposability of some simplicial complexes and Stanley’s conjectures.",signatures:"Seyed Mohammad Ajdani and Francisco Bulnes",downloadPdfUrl:"/chapter/pdf-download/80019",previewPdfUrl:"/chapter/pdf-preview/80019",authors:[{id:"92918",title:"Dr.",name:"Francisco",surname:"Bulnes",slug:"francisco-bulnes",fullName:"Francisco Bulnes"},{id:"440971",title:"Dr.",name:"Seyed",surname:"Mohammad Ajdani",slug:"seyed-mohammad-ajdani",fullName:"Seyed Mohammad Ajdani"}],corrections:null},{id:"79892",title:"βI-Compactness, βI*-Hyperconnectedness and βI-Separatedness in Ideal Topological Spaces",doi:"10.5772/intechopen.101524",slug:"-em-em-sub-em-i-em-sub-compactness-em-em-sub-em-i-em-sub-hyperconnectedness-and-em-em-sub-em-i-em-su",totalDownloads:85,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Let XτI be an ideal topological space. A subset A of X is said to be β-open if A⊆clintclA, and it is said to be βI-open if there is a set O∈τ with the property 1 O−A∈I and 2 A−clintclO∈I. The set A is called βI-compact if every cover of A by βI-open sets has a finite sub-cover. The set A is said to be cβI-compact, if every cover Oλ:λ∈Λ of A by β-open sets, Λ has a finite subset Λ0 such that A−∪Oλ:λ∈Λ0∈I. The set A is said to be countably βI-compact if every countable cover of A by βI-open sets has a finite sub-cover. An ideal topological space XτI is said to be βI∗-hyperconnected if X−cl∗A∈I for every non-empty βI-open subset A of X. Two subsets A and B of X is said to be βI-separated if clβIA∩B=∅=A∩clβB. Moreover, A is called a βI-connected set if it can’t be written as a union of two βI-separated subsets. An ideal topological space XτI is called βI-connected space if X is βI-connected. In this article, we give some important properties of βI-open sets, βI-compact spaces, cβI-compact spaces, βI∗-hyperconnected spaces, and βI-connected spaces.",signatures:"Glaisa T. Catalan, Michael P. Baldado Jr and Roberto N. Padua",downloadPdfUrl:"/chapter/pdf-download/79892",previewPdfUrl:"/chapter/pdf-preview/79892",authors:[{id:"425714",title:"Prof.",name:"Michael",surname:"Baldado",slug:"michael-baldado",fullName:"Michael Baldado"},{id:"438024",title:"Dr.",name:"Glaisa",surname:"Catalan",slug:"glaisa-catalan",fullName:"Glaisa Catalan"},{id:"486473",title:"Dr.",name:"Roberto N.",surname:"Padua",slug:"roberto-n.-padua",fullName:"Roberto N. Padua"}],corrections:null},{id:"79797",title:"Clairaut Submersion",doi:"10.5772/intechopen.101427",slug:"clairaut-submersion",totalDownloads:86,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"In this chapter, we give the detailed study about the Clairaut submersion. The fundamental notations are given. Clairaut submersion is one of the most interesting topics in differential geometry. Depending on the condition on distribution of submersion, we have different classes of submersion such as anti-invariant, semi-invariant submersions etc. We describe the geometric properties of Clairaut anti-invariant submersions and Clairaut semi-invariant submersions whose total space is a Kähler, nearly Kähler manifold. We give condition for Clairaut anti-invariant submersion to be a totally geodesic map and also study Clairaut anti-invariant submersions with totally umbilical fibers. We also give the conditions for the semi-invariant submersions to be Clairaut map and also for Clairaut semi-invariant submersion to be a totally geodesic map. 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Saleh",coverURL:"https://cdn.intechopen.com/books/images_new/9873.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"144691",title:"Prof.",name:"Hosam M.",middleName:null,surname:"Saleh",slug:"hosam-m.-saleh",fullName:"Hosam M. Saleh"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"166445",title:"Prof.",name:"Aziz",middleName:null,surname:"Hasib",fullName:"Aziz Hasib",slug:"aziz-hasib",email:"azhasib@yahoo.fr",position:null,institution:null},{id:"237725",title:"Prof.",name:"Reda",middleName:null,surname:"Elkacmi",fullName:"Reda Elkacmi",slug:"reda-elkacmi",email:"redakcm@gmail.com",position:null,institution:null},{id:"325462",title:"Dr.",name:"Abdellah",middleName:null,surname:"Ouigmane",fullName:"Abdellah Ouigmane",slug:"abdellah-ouigmane",email:"ouigmaneabdellah@gmail.com",position:null,institution:null},{id:"325463",title:"Prof.",name:"Otmane",middleName:null,surname:"Boudouch",fullName:"Otmane Boudouch",slug:"otmane-boudouch",email:"oboudouch@gmail.com",position:null,institution:null},{id:"325528",title:"Prof.",name:"Mustapha",middleName:null,surname:"Bouzaid",fullName:"Mustapha Bouzaid",slug:"mustapha-bouzaid",email:"bozidstof@yahoo.fr",position:null,institution:null},{id:"325529",title:"Prof.",name:"Mohammed",middleName:null,surname:"Berkani",fullName:"Mohammed Berkani",slug:"mohammed-berkani",email:"m.berkani@gmail.com",position:null,institution:null}]},book:{id:"9873",title:"Strategies of Sustainable Solid Waste Management",subtitle:null,fullTitle:"Strategies of Sustainable Solid Waste Management",slug:"strategies-of-sustainable-solid-waste-management",publishedDate:"April 21st 2021",bookSignature:"Hosam M. Saleh",coverURL:"https://cdn.intechopen.com/books/images_new/9873.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"144691",title:"Prof.",name:"Hosam M.",middleName:null,surname:"Saleh",slug:"hosam-m.-saleh",fullName:"Hosam M. Saleh"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}}},ofsBook:{item:{type:"book",id:"11793",leadTitle:null,title:"Production, Nutritional and Industrial Perspectives of Barley",subtitle:null,reviewType:"peer-reviewed",abstract:"
\r\n\tIn this book, the technological and functional properties of barley will be highlighted comprehensively. Moreover, Nutritional and bioactive profiles and barley utilization in different baking products will also be in the limelight of this book. This depiction will be valuable for all consumers from health points of view.
\r\n\r\n\tFood security is an alarming issue in developing countries as the population is increasing day by day. So, researchers have to think about alternative sources of staple diet(wheat) that should have the same nutritional composition as compared to wheat. Among cereals, barley is an alternative source because of its nutritional and functional properties, despite all the functional ingredients it is rarely used in the food industry. From different researches, it is revealed that it contains 24 % dietary fiber, so it is beneficial for CVDs and other health-related disorders. Now a day, barley consumption is very rare. There are many barley products in the food market such as malt flour, grits, flakes, pot, and pearled barley. Bread formulations also involve the usage of barley flour and cracked barley. The possibility of high fiber barley utilization in breakfast cereals production through blending with other grains, flaking, puffing, and extrusion is becoming common. So, there is a dire need to do value addition of barley into various products. Furthermore, the most important reason for wheat replacement with barley is its allergy-causing nature in some cases. Keeping in view all of the above facts, the present book has been designed.
",isbn:"978-1-80356-924-6",printIsbn:"978-1-80356-923-9",pdfIsbn:"978-1-80356-925-3",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,isSalesforceBook:!1,isNomenclature:!1,hash:"996125d4599193b3b6b749f5d8aa3cb2",bookSignature:"Dr. Farhan Saeed and Dr. Muhammad Afzaal",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11793.jpg",keywords:"Cereal, Barley, Dietary Fibers, Nutritional Composition, Grains, Technology, Processing, Milling, Flour, Rheology, Bioactive Profile, Utilization",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"April 6th 2022",dateEndSecondStepPublish:"June 14th 2022",dateEndThirdStepPublish:"August 13th 2022",dateEndFourthStepPublish:"November 1st 2022",dateEndFifthStepPublish:"December 31st 2022",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"2 months",secondStepPassed:!0,areRegistrationsClosed:!0,currentStepOfPublishingProcess:4,editedByType:null,kuFlag:!1,biosketch:"Dr. Farhan is an Assistant Professor at Government College University Faisalabad-Pakistan where he finished his Ph.D. at the age of 28 years. He has an h index of 16 and has published more than 70 papers in reputed journals with an impact factor of more than 140. His research focus is on finding innovative and effective practices to improve food production, quality, and safety, keeping in view the betterment of human health.",coeditorOneBiosketch:"Dr. Muhammad Afzaal is working as an Assistant professor in the Department of Food Science. Government College University Faisalabad. He has 10 years of teaching and research experience. He has more than 40 publications in well-reputed journals and 5 book chapters published. His research interests are food science and technology, food microbiology and biotechnology, microencapsulation, probiotics, prebiotics & synbiotics, biopreservation, and waste value addition.",coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"192244",title:"Dr.",name:"Farhan",middleName:null,surname:"Saeed",slug:"farhan-saeed",fullName:"Farhan Saeed",profilePictureURL:"https://mts.intechopen.com/storage/users/192244/images/system/192244.jpg",biography:"PERSONAL STATEMENT\r\nMy name is Farhan Saeed. During Master study, I received an Indigenous Fellowship from Higher Education Commission (HEC) Pakistan. The selection process was a rigorous process starting from a GRE-based test. After being short listed by HEC, part of the Fellowship was the opportunity to complete doctorate degree mainly within Food Science and Technology field. I did my Doctorate thesis entitled 'Biochemical characterization of non-starch polysaccharides in relation to end-use quality of spring wheats” under the supervision of Dr. Imran Pasha. The doctorate research was focused on value addition of bioactive components extracted from spring wheats. The addition of extracted non-starch polysaccharides enhances the quality of baked products as well as important in nutraceutical point of view. The products under proposed study were thoroughly investigated for assessment of nutritional and end use quality of bread. The output of the proposed research work was highly beneficial to the consumers as well as Government of Pakistan for their intended purposes. The awareness about nutritional significance of non-starch polysaccharides enriched bread was really set the new horizons in product development in Pakistan. In 2012, I joined Institute of Home & Food Sciences, Government College University Faisalabad as Assistant Professor. In 2014, I became HEC Approved Supervisor. During 2015, I have visited Massachusetts, Amherst, USA under Pakistan Program for Collaborative Research (PPCR), HEC Pakistan for two months training program for the development of innovative project. After that, I have been selected to receive a 2016 'Endeavour Research Fellowship” to undertake proposed program in Australia. I did work in Centre for Nutrition & Food Science, The University of Queensland, Brisbane, Australia under the supervision of Professor Mike Gidley. The commencing date of current program is May 17, 2016 and the expiry is on November 15, 2016. In October, 2018. I was promoted to Tenured Associate Professor. I have published more than 70 papers in reputed journals with impact factor more than 140. I have 20 book chapters in international books. I presented research works in international level at Huazhong University Wuhan, China and Conference on Food Properties in Sharjah. I also got two research projects funds from Higher Education Commission Islamabad, Pakistan. I would like to be granted the KGSP because it will offer me with the opportunity to partake in Post-Doctoral program of Food Science and Biotechnology at Kyungpook National University (KNU) among the best universities in Korea. In my home country, vital issues stressed in this particular degree program are quite overlooked, and this scholarship program will bring me a great chance to come within reach of them. By taking this course, I am optimistic for finding innovative and effective practices to improve food production, quality and safety, keeping in view the betterment of human health; and moreover, to improve the end-product quality for maintenance of customer’s health. To sum up, winning the KGSP will enable me not only to broaden my knowledge, but also to gain experience from people and culture of both countries Korea and Pakistan. In the longer term, I sturdily desire to contribute to the cause of assuring food security and safety initially in my country and laterally worldwide. The main objective of applying here to get international exposure while working with world class food experts especially those working in the area of functional foods and nutraceuticals. The knowledge and expertise together with the international interaction developed through this project will finally be utilized for the development of laboratory of functional foods and nutraceuticals at my home institute.",institutionString:"Government College University, Faisalabad",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Government College University, Faisalabad",institutionURL:null,country:{name:"Pakistan"}}}],coeditorOne:{id:"245894",title:"Dr.",name:"Muhammad",middleName:null,surname:"Afzaal",slug:"muhammad-afzaal",fullName:"Muhammad Afzaal",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSF1qQAG/Profile_Picture_1618812051691",biography:"Dr. Muhammad Afzaal, Ph.D., is an Assistant Professor in the Department of Food Science, Government College University Faisalabad, Pakistan. He is involved in various additional assignments as a Business Manager-BIC (Food & Services), and Lab Incharge (Food Safety and Biotechnology). He has about 10 years of teaching and research experience. Dr. Afzaal has been a part of many national and international research projects. His research interests are Food Science & Technology, Food microbiology & Biotechnology, Hydrogels, Encapsulation, Probiotics, and Biopolymer. Dr. Muhammad Afzaal completed his Ph.D. in Food Science and Technology from GC University Faisalabad. His doctorate research focus was on the development of functional foods containing encapsulated probiotics with improved viability. Dr. Afzaal is also working on various carbohydrates, protein, and lipid-based encapsulation wall materials to elucidate their key role in the viability and stability of probiotics under stressed conditions. He is HEC approved supervisor since 2019. He has executed many research projects as a team member and Coordinator. Dr. Afzaal is a life member of the Pakistan Society of Food Scientists & Technologists (PSFST) and General Secretary of Faisalabad- PSFST chapter.",institutionString:"Government College University, Faisalabad",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Government College University, Faisalabad",institutionURL:null,country:{name:"Pakistan"}}},coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"5",title:"Agricultural and Biological Sciences",slug:"agricultural-and-biological-sciences"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"252211",firstName:"Sara",lastName:"Debeuc",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/252211/images/7239_n.png",email:"sara.d@intechopen.com",biography:"As an Author Service Manager my responsibilities include monitoring and facilitating all publishing activities for authors and editors. From chapter submission and review, to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. Whether that be identifying an exceptional author and proposing an editorship collaboration, or contacting researchers who would like the opportunity to work with IntechOpen, I establish and help manage author and editor acquisition and contact."}},relatedBooks:[{type:"book",id:"6418",title:"Hyperspectral Imaging in Agriculture, Food and Environment",subtitle:null,isOpenForSubmission:!1,hash:"9005c36534a5dc065577a011aea13d4d",slug:"hyperspectral-imaging-in-agriculture-food-and-environment",bookSignature:"Alejandro Isabel Luna Maldonado, Humberto Rodríguez Fuentes and Juan Antonio Vidales Contreras",coverURL:"https://cdn.intechopen.com/books/images_new/6418.jpg",editedByType:"Edited by",editors:[{id:"105774",title:"Prof.",name:"Alejandro Isabel",surname:"Luna Maldonado",slug:"alejandro-isabel-luna-maldonado",fullName:"Alejandro Isabel Luna Maldonado"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10359",title:"Landraces",subtitle:"Traditional Variety and Natural Breed",isOpenForSubmission:!1,hash:"0600836fb2c422f7b624363d1e854f68",slug:"landraces-traditional-variety-and-natural-breed",bookSignature:"Amr Elkelish",coverURL:"https://cdn.intechopen.com/books/images_new/10359.jpg",editedByType:"Edited by",editors:[{id:"231337",title:"Dr.",name:"Amr",surname:"Elkelish",slug:"amr-elkelish",fullName:"Amr Elkelish"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1591",title:"Infrared Spectroscopy",subtitle:"Materials Science, Engineering and Technology",isOpenForSubmission:!1,hash:"99b4b7b71a8caeb693ed762b40b017f4",slug:"infrared-spectroscopy-materials-science-engineering-and-technology",bookSignature:"Theophile Theophanides",coverURL:"https://cdn.intechopen.com/books/images_new/1591.jpg",editedByType:"Edited by",editors:[{id:"37194",title:"Dr.",name:"Theophile",surname:"Theophanides",slug:"theophile-theophanides",fullName:"Theophile Theophanides"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3161",title:"Frontiers in Guided Wave Optics and Optoelectronics",subtitle:null,isOpenForSubmission:!1,hash:"deb44e9c99f82bbce1083abea743146c",slug:"frontiers-in-guided-wave-optics-and-optoelectronics",bookSignature:"Bishnu Pal",coverURL:"https://cdn.intechopen.com/books/images_new/3161.jpg",editedByType:"Edited by",editors:[{id:"4782",title:"Prof.",name:"Bishnu",surname:"Pal",slug:"bishnu-pal",fullName:"Bishnu Pal"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"371",title:"Abiotic Stress in Plants",subtitle:"Mechanisms and Adaptations",isOpenForSubmission:!1,hash:"588466f487e307619849d72389178a74",slug:"abiotic-stress-in-plants-mechanisms-and-adaptations",bookSignature:"Arun Shanker and B. 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The American Society for Aesthetic Plastic Surgery reported that in 2016 in the USA 17.1 million surgical and nonsurgical cosmetic procedures were performed, a figure that indicates a 132% increase since 2000. These procedures represented an expenditure of approximately 16.4 billion US dollars, where breast augmentation is the most popular surgery and the application of Botox is the most performed nonsurgical procedure [1]. Other interesting aspects that have grown around plastic surgery are ambulatory surgery units, short-stay units, and procedures performed in plastic surgeons’ medical offices. It is important that anesthesiological care does not decline when surgery is performed in this type of facility and the media and plastic surgeons must be made aware, so they do not minimize the risks of this type of surgery, which from the point of view of the anesthesiologists are medium- and high-risk procedures [2, 3]. Regardless of where the surgery is performed, patient safety should be the primary issue at the time of anesthesia-surgery and during its immediate recovery. To ensure patient safety, there are several guidelines that list the most important points of accomplishment that should be followed in this regard. The published guide from SCARE [4], which emphasizes various points of safety, especially the mechanical and pharmacological prophylaxis of deep venous thrombosis (DVT) and pulmonary thromboembolism (PE). A review of the literature on liposuction complications establishes strict guidelines on lidocaine and epinephrine doses, PE prophylaxis, adequate hydration, and other management recommendations [5].
The advances in plastic surgery have been furthered by the progress in anesthesiology, making it the cornerstone on which the surgical progress has been made. Now, it is possible to carry out prolonged and more elaborate surgeries in patients with concomitant pathologies or with anesthesia risks that some years ago were not possible to achieve with the current safety. The availability of new anesthetics and adjuvant drugs, advances in trans- and postoperative monitoring, as well as the early prevention of complications have facilitated these advances. The list of plastic surgical procedures is very extensive, and anesthesia plays a vital role: from local techniques to neuraxial anesthesia and general inhaled or intravenous anesthesia procedures. The growth of outpatient procedures in cosmetic surgery requires effective anesthetic techniques that allow safe home returns shortly after the surgery is over. It is ideal that no surgical procedure in plastic surgery is performed without the presence of a qualified anesthesiologist.
This chapter serves as an introduction to this book, the most frequent plastic surgery procedures are listed, as well as the anesthesia techniques considered to be the most advanced.
It is important that the anesthesiologist be familiar with all surgical procedures to establish an optimal anesthetic approach (see Graphic 1 and Tables 1 and 2). It is also important to keep in mind that the original surgical plan changes frequently; these last-minute modifications obey the wishes of the patient and sometimes the needs that arise during surgery, situations that lead to adjust the original anesthetic plan.
Most frequent cosmetic surgeries.
Surgery | Women | Men |
---|---|---|
Breast augmentation | 355, 671 | |
Liposuction | 309,692 | 31,453 |
Blepharoplasty | 166,426 | 28,678 |
Abdominoplasty | 143,005 | |
Breast reduction | 139,926 | |
Rhinoplasty | 30,174 | |
Gynecomastia | 19,124 | |
Hair implantation | 18,062 |
Most frequent procedures according to gender [1].
Procedures | Anesthesia | Patient stay | Observations |
---|---|---|---|
• Facial surgery | |||
Rhytidoplasty | CS/GA | 24 hours | Moderate pain |
Coronal | CS/GA | Ambulatory | Fast track |
Open rhinoplasty | CS/GA | Ambulatory | Fast track |
Rhinoplasty with bone fracture | GA | Ambulatory | Moderate pain |
Blepharoplasty | MAC/CS | Ambulatory | Fast track |
Otoplasty | MAC/CS | Ambulatory | Fast track |
Laser dermabrasion | CS | Ambulatory | Moderate pain |
Implants | MAC/CS | Ambulatory | Fast track |
Fat grafting, synthetic materials | MAC/CS | Ambulatory | Fast track |
• Body surgery | |||
Breasts or pectorals | PDB/GA | Ambulatory | Moderate pain |
Liposuction | SB, PDB, GA, or local | Ambulatory −24 hours | Mild to moderate pain, bleeding, anemia |
Torso | PDB /GA | Ambulatory | Moderate pain |
Abdominoplasty | SB, PDB/GA | 24 hours | Moderate pain, anemia |
Breast pexia of inferior segment | PDB/GA | 24 hours | Moderate pain, anemia |
Buttocks implants | SB/PDB/GA | Ambulatory | Moderate pain |
• Limb surgery | |||
Brachioplasty | PDB/GA | Ambulatory | Moderate pain |
Cruroplasty | SB/PDB/GA | Ambulatory −24 hours | Moderate pain |
Liposuction | SB/PDB/GA | Ambulatory | Mild pain |
Most frequent procedures in cosmetic surgery.
CS = conscious sedation; GA = general anesthesia; PDB = peridural block; SB = spinal block; MAC = monitored anesthetic care; fast track = direct access to hospital room.
Table 2 lists the most frequent surgical procedures in plastic surgery and relates them to the most used anesthesia techniques, making some important observations in postanesthetic care and evolution. These techniques are the most recommended, being possible to use other alternatives or through combinations of anesthetic methods [6].
In plastic surgery, it is common to combine two or more surgical procedures (breast-abdominoplasty, mommy makeover), which in addition to increasing the risks, prolongs the surgical time, and therefore the anesthetic plan must be adapted to the surgeon’s new approach. This fact can be determined before starting anesthesia, and in some patients, it is modified during surgery. For example, in a case where breast surgery is combined with abdomen procedures that could otherwise be managed with neuraxial anesthesia, a lumbar spinal anesthesia with hyperbaric local anesthetic and Trendelenburg position could disseminate the blockade up to T3 for breast surgery, which must be performed first, followed by the abdominal procedure [7]. This approach avoids general anesthesia and favors adequate postoperative analgesia with optimal recovery. Combined epidural-spinal anesthesia is another management option in this surgical setting.
“Primum non nocere” is a Latin phrase meaning “first, to do no harm” and is an old statement that has been one of the principal precepts of bioethics for several centuries. This concept is the purpose of pre-anesthetic assessment, which in patients scheduled for plastic surgery should not be any different from that of patients operated of other procedures and should be timely, complete, interdisciplinary, and dynamic. This evaluation is a vital instrument for the medical and nursing team, as well as for the patients and their families since it gives them the opportunity to know the patient and their environment, the reasons that led to surgery, fears of, and above all, to discuss the prejudices and doubts about anesthesia. These patients have peculiarities that make them different; on the one hand, most are healthy people, individuals who do not intend to cure a disease but to improve their self-esteem through better physical appearance. On the other hand, they are extremely demanding patients in terms of perfection in the results and do not tolerate errors or side effects. It is prudent to explain the various anesthetic techniques available for the type of surgery scheduled, as well as the benefits and risks of each anesthetic procedure, especially those attributed to the planned technique. It is also the best time for them to meet the anesthesiologist and become familiar with his/her credentials and experience. These last points are fundamental to gain patient confidence and to diminish their anxiety and the possibility of an eventual legal conflict.
The pre-anesthetic evaluation should be made several days in advance. Regardless of the physical condition of each patient, a complete clinical history and detailed and oriented physical examination are fundamental in the pre-anesthetic assessment. It is essential to determine the physical integrity or possible deterioration of the patient, especially the neurological and cardiopulmonary systems, as well as a detailed analysis of the airway and the spine. The patients must be evaluated regarding their emotional state and their ability to tolerate surgeries with prolonged times and difficult recoveries. Plastic surgery patients are divided into two major categories: healthy patients and patients with one or more systemic pathologies, such as acquired heart diseases, pneumopathies, diabetes mellitus, venous insufficiency, and hyperlipidemia, this last one being the most common. The age at which cosmetic surgery is performed is variable: 35–50 years (45%), 51–64 years (26%), 19–34 (22%), 65 or more (6%), and minors to 18 years (2%) [3].
During this pre-anesthetic interview, the intake of medications such as nonsteroidal anti-inflammatory drugs (NSAIDs), vitamin E, weight loss medications, contraceptives, herbs, as well as history of illegal drug use or any prescription medicines should be questioned. It is frequent that these “healthy” patients utilize thyroid hormones, antidepressants, benzodiazepines, high doses of vitamins and minerals, as well as herbs, food supplements, and teas that could interact with the drugs used in the perianesthesiological time. Patients underestimate the importance to ingest these products, so it is imperative that both the surgeon and the anesthesiologist emphatically investigate whether patients ingest such products since many of them have anticoagulant, antiplatelet, procoagulant, and arrhythmic or potentiate the effects of anesthetics. Heller et al. [10] found that plastic surgery patients used herbs or supplements in 55% versus the general population 24% (p < 0.001). The most used by their patients were chondroitin 18%, ephedra 18%, echinacea 8%, garlic 6%, ginseng 4%, and ginger 4%. Fifty-four percent of the supplements/herbs taken by these patients have pharmacological interference with anesthetic drugs or can affect surgery. In 85% of the cases, patients were not told to stop taking these herbs or supplements before surgery, except for those who ingested ephedra in which 100% of the surgeons indicated their suspension. This study demonstrated the ignorance of physicians regarding the undesirable effects of herbalism in plastic surgery patients. A Mexican study in ambulatory patients [11] found that 65% took ginseng and
Product | Effect | Product | Effect |
---|---|---|---|
Fish oil | Antiplatelet, vasodilation | Kava ( | Interacts with local anesthetics, barbiturates, increase sedative potency |
Garlic ( | Antiplatelet | St. John’s wort ( | Induces cytochrome P450 3A4. Interacts with midazolam, alfentanil, lidocaine, calcium blockers, and serotonin receptor agonists |
Alfalfa ( | Anticoagulant Enhances warfarin and ginger effect | Ginseng ( | Anticoagulant |
Dong quai | Anticoagulant, antiplatelet | Wild lettuce | Enhances warfarin |
Anise | Anticoagulant | Black cohosh | Antiplatelet |
Celery | Antiplatelet | Arnica | Anticoagulant |
Saffron | Anticoagulant | Papain (papaya proteinase I) | Hemorrhage risk |
Boldo ( | Enhances warfarin | Kelp | Anticoagulant |
Bromelain | Anticoagulant | Coagulant | |
Anticoagulant | Horseradish | Anticoagulant | |
Onion | Antiplatelet | Licorice root ( | Antiplatelet |
Clove | Antiplatelet | Red clover | Anticoagulant |
Chili pepper (Nahuatl chili) | Antiplatelet | Turmeric ( | Antiplatelet |
Ephedra | Vasoconstriction, cardiac infarction, cerebral thrombosis, arrhythmias, hypertension | Increases sedative effect | |
Echinacea | Promotes infections, allergies, probable hepatotoxic and impaired blood flow | Vitamin E | Antiplatelets |
Gingko biloba | Antiplatelet | Asiatic ginseng | Anticoagulant, antiplatelets, hypoglycemic |
Effects of some herbs and foods.
Elderly patients require a more elaborate evaluation, in which it is wise to include the geriatrician. In this group of sick patients, a list that includes all the medications they take should be made, including antihypertensive, diuretic, vasodilator, MAO inhibitors, antidepressants, analgesics, hormones, hypoglycemic agents, vitamins and minerals, etc. The anesthesiologist must be familiar with these drugs and know their possible drug interactions. The usual pre-anesthetic assessment parameters in healthy patients and patients with comorbidities are listed in Table 4.
Parameters | ASA 1 | ASA 2–3 | Observations |
---|---|---|---|
Clinical history | Yes | Yes | The general and oriented clinical review made by the anesthesiologist anticipates problems such as difficult airway, spinal anomalies, mental alterations, family environment, and possibility of a lawsuit |
Physical examination | Yes | Yes | |
Specialist consultation | NE | Yes | It is prudent to know the opinion of the geriatrician, pulmonologist, cardiologist, endocrinologist, surgeon, and family therapist in search of polypharmacy, drug interactions, etc. |
Electrocardiogram | Only >50 years old | Yes | Arrhythmias, ischemia, growth, or dilatation of heart cavities |
Chest X-ray | NE | Yes | Useful in smokers, suspected tuberculosis, neoplasms, emphysema, kyphosis |
Echocardiogram | No | R | Compulsory study in patients with severe arterial hypertension, ischemic patients, and patients with dilated cardiomyopathy |
Spirometry | No | R | Its usefulness has not been demonstrated; however, it is recommended in chronic pneumopathy and smokers |
Blood test | Yes | Yes | Diagnosis of subclinical anemia |
Coagulation tests | Yes | Yes | TP, TPT, INR, and bleeding time are mandatory in anticoagulants, hepatocellular damage, severe sepsis, prolonged fasting, and extreme malnutrition |
Complete blood chemistry | Yes | Yes | Kidney, hepatocellular, metabolic, and electrolyte evaluation |
Urinalysis | NE | Yes | Loss of blood and proteins, changes in urine density |
HIV, hepatitis, drugs, pregnancy | R | R | They are requested based on the clinical history and experience data. HIV is prudent for the protection of medical and paramedical personnel |
Parameters for pre-anesthetic evaluation in plastic surgery [5].
NE = not essential; R = recommendable.
There are patients who should not be operated, and this decision must be made by the anesthesiologist, regardless of the opinion of the patient and his/her surgeon since loss of safety rules leads to catastrophic nonreversible events [14].
Once the anesthetic assessment has been finalized and the best anesthetic plan has been agreed upon and the possible eventualities discussed, the informed consent must be obtained, which as a rule must be signed by the patient, the doctor, and a witness. This document should mention the details of the proposed anesthetic technique, its side effects, and possible complications in a detailed manner. A well-prepared informed consent is a legal document that does not exclude us from a lawsuit, but when it is not done properly, it can be a legal component against the medical team [14, 15, 16].
The goal of pre-anesthetic medication is to help the patient to arrive to the operating room with sedation, hypnosis, prevention of nausea and vomiting, and with preemptive analgesia. Midazolam and lorazepam are the most commonly used benzodiazepines. Midazolam is more useful in short procedures, although it is less amnesic than lorazepam. There is evidence that melatonin 3–10 mg administered as part of pre-anesthetic medication reduces preoperative anxiety, decreases postoperative pain intensity and opioid consumption, improves postoperative sleep quality, and reduces emergence behavior and postoperative delirium. Also, preoperative melatonin could reduce oxidative stress and anesthetic requirements [17, 18, 19, 20]. To prevent nausea and vomiting, it is advisable to use two or more drugs [21]; combining droperidol with dexamethasone is as effective as the combination of ondansetron with dexamethasone. Metoclopramide tends to disappear due to its low clinical effectiveness compared to the new antiemetics. It is convenient to administer omeprazole or ranitidine to reduce the acidity and volume of the gastric secretion. Preemptive analgesia is achieved with the administration of various drugs such as intravenous magnesium, NSAIDs, gabapentinoids, and ketamine to name a few.
In general terms, regional anesthesia techniques are more recommendable than those of general anesthesia since they have less complications and favor a safer recovery, with better postoperative analgesia. In the following paragraphs, several anesthetic procedures are discussed and are related primarily to outpatient surgery since most plastic surgery patients are discharged the same day of their intervention. Figure 1 shows all the anesthetic techniques that can be used in plastic surgery procedures, a wide range of combinations being possible.
Anesthesia techniques that can be used for plastic surgery.
For more details of some anesthetic technique, the reader is referred to the pertinent chapters of this book.
The objective of conscious sedation is to have a patient in a status of restfulness that allows the surgeon to inject local anesthetics and perform their operative procedure with safety and comfort for the patient, while the anesthesiologist is responsible for drug sedation and checking the stability of all systems using conventional monitoring and added BIS. The most frequent surgeries are those of the face and neck, hair implants, liposuction of small areas, dermabrasion with laser, and occasionally breast implants. A clear understanding must be established with the patient and the surgeon about the objectives of conscious sedation:
Spectrum of alertness, conscious sedation, deep sedation, and general anesthesia [
There are several types of drugs that are used in conscious sedation: anxiolytics, sedatives, butyrophenones, barbiturates, hypnotics, opioids, and alpha2 agonists (Table 5).
Anesthesia techniques | Opioids | Benzodiazepines | Hypnotics | Alpha-2 | Anesthetic gases | Muscle relaxants |
---|---|---|---|---|---|---|
TIVA | Fentanyl, remifentanil, alfentanil | Midazolam | Propofol, ketamine | Dexmedetomidine | Nitrous oxide | Vecuronium rocuronium, atracurium |
General | Fentanyl Morphine | Midazolam, diazepam | Propofol, ketamine, thiopental | Clonidine, dexmedetomidine | Desflurane Sevoflurane Isoflurane | Vecuronium rocuronium, atracurium |
Conscious sedation | Fentanyl Remifentanil Morphine Buprenorphine | Midazolam, lorazepam | Propofol, ketamine, barbiturates | Clonidine, dexmedetomidine | No | No |
TCI | Remifentanil | No | Propofol | No | No | No |
Anesthesia techniques and examples of usual drugs.
MAC = monitored anesthetic care; TCI = target-controlled infusion.
The 2018 ASA guidelines for sedation added the following recommendations: patient evaluation and preparation, continual monitoring of ventilatory function with capnography to supplement standard monitoring by observation and pulse oximetry, presence of an individual in the procedure room with knowledge and skills to recognize and treat airway complications, sedatives and analgesics not intended for general anesthesia (e.g., benzodiazepines and dexmedetomidine), sedatives and analgesics intended for general anesthesia (e.g., propofol, ketamine, and etomidate), recovery care, and creation and implementation of quality improvement processes [22].
General anesthesia can be used in all plastic surgery procedures if the location where they have been scheduled fulfills with all safety regulations. This rule should not be violated, especially in medical offices that have been supplemented with an operating room (office based). General anesthesia techniques are used in very short procedures, in patients who reject regional techniques, and as a complement to regional anesthesia when this is not sufficient. In prolonged surgeries of more than 3 hours, it is prudent to avoid the use of general anesthesia when this is possible to prevent risks and undesirable side effects such as nausea, vomiting, oropharyngeal discomfort secondary to the endotracheal tube or laryngeal mask, DVT, PE, postoperative pain, postoperative delirium, and so on. The costs of general anesthesia, although not a definitive factor, do influence the anesthesiological decision, particularly when the procedures are very long. The selection of patients for general anesthesia must be meticulous and exclude those cases with associated pathologies: angina, recent history of cardiac infarction, cardiomyopathies, uncontrolled arterial hypertension, terminal renal failure, sickle cell anemia, patients in need of organ transplantation, active multiple sclerosis, severe chronic obstructive pulmonary disease, difficult airway, malignant hyperthermia, abuse of illegal drugs, dementia, myasthenia gravis, obstructive sleep apnea, and etcetera [23, 24]. In some of these associated pathologies, it is possible to perform plastic surgery; however, precautions must be taken for each disease due to potential complications.
When general anesthesia has been chosen, the drugs to be used should be selected for safety and anesthetic efficacy, in accordance with the surgical location. The ideal technique does not exist, but it must be ensured that it is with a gentle and rapid induction, with adequate operative conditions, with great hemodynamic stability and fast recovery, without side effects, with good control of postsurgical acute pain, with emesis, and with preventive management of postoperative chronic pain. There is not enough evidence to select one drug over another; however, the halogenated anesthetics desflurane, sevoflurane, and isoflurane have demonstrated their versatility in outpatients with a minimum of differences that do not impact the transoperative evolution or the recovery of patients [23, 25]. It is convenient to avoid nitrous oxide due to the high incidence of postoperative nausea and vomiting. Propofol, ketamine, and remifentanil have been widely accepted in this field, each of them having certain advantages. The combination of propofol-ketamine has been studied by Friedberg [25] and proposed as an alternative to inhalational anesthesia.
Regional anesthesia has had an increasing resurgence since it favors several positive aspects in the trans, operative period, and in the recovery phase. Local anesthesia is performed by the plastic surgeon in cases of minimal invasion such as blepharoplasty, chin implant, and some small liposuction among other procedures. Neuraxial anesthesia, especially spinal anesthesia, has been favored by its advantages (Table 6). Capdevila and Dadure [26] consider that the various techniques of regional anesthesia, including spinal anesthesia, are superior to general anesthesia in limiting adverse effects and readmissions to the hospital, with better control of postoperative pain [27]. In the following paragraphs, subarachnoid and epidural block are described, although the latter is less used because it has more possibilities of undesirable effects.
General | Sedation | Peridural | Spinal | Combined | PNB* | |
---|---|---|---|---|---|---|
Bleeding | ++++ | ++ | ++ | ++ | + a ++ | + a ++ |
DVT/TEP risk | High | Low | Low | Low | Low | Low |
Anesthetic toxicity | Remote | Remote | Feasible | Very remote | Feasible | Feasible |
Hypoxia PO | Frequent | Possible | Possible | Possible | Possible | Possible |
Analgesia PO | No | No | Yes | Yes | Yes | Yes |
Technical difficulty | Remote | No | Possible | Possible | Possible | Frequent |
Cognitive disorders | ++++ | ++ | ++ | ++ | + | No |
Cost | High | High | Medium | Low | High | High |
Advantages and disadvantages of the different techniques in anesthesia for plastic surgery.
Peripheral nerve block.
Neuraxial blocks offer several advantages over general anesthesia, as shown in Table 6. The decrease in metabolic response to trauma, postoperative analgesia, lower incidence of nausea and postoperative vomiting, and their low costs are just some of these advantages.
Surgery | Spinal | Epidural | APEC | |||
---|---|---|---|---|---|---|
Anesthetic | Adjuvant | Anesthetic | Adjuvant | Anesthetic | Adjuvant | |
Liposuction | L, B, LB, R, M | C, F | L, R, B, LB, M | C, F | L, R,B, LB, M | C, F, S |
Liposculpture | B, LB, R, M | C, F | L, R, B, LB, M | C, F | L, R,B, LB, M | C, F, S |
Buttocks implants | L, B, LB, R, M | C | L, B, LB, R, M | C | L, R,B, LB, M | C, F, S |
Calf implants | L, B, LB, R, M | C | L, B, LB, R, M | C | L, R,B, LB, M | C, F, S |
Breast with liposuction | B, LB, R, M | C, F | L, R, B, LB, M | C, F | L, R,B, LB, M | C, F, S |
Breast | — | — | L, R, B, LB, M | no | — | — |
Frequent procedures and regional techniques in ambulatory cosmetic surgery [20].
APEC = combined peridural-spinal anesthesia; L = lidocaine; B = racemic bupivacaine; LB = levobupivacaine; R = ropivacaine; M = mepivacaine; C = clonidine; F = fentanyl; S = sufentanil.
Surgery | Concentration of local anesthetic and total dose in mg | |||
---|---|---|---|---|
Ropivacaine (0.75%) | Levobupivacaine (0.75%) | Bupivacaine (0.5–0.75%) | Lidocaine (2%) | |
Liposuction | 10–22.5 | 7.5–18 | 7.5–15 | 50–100 |
Liposculpture | 10–22.5 | 7.5–18 | 7.5–15 | 50–100 |
Buttocks implants | 15 | 10 | 10 | 100 |
Calf implants | 15 | 10 | 10 | 100 |
Breast with liposuction | 22.5 | 18 | 18 | No |
When the scheduled plastic surgery is longer than 2 hours, it is advisable to add an adjuvant drug such as clonidine in doses of 75, 150–300 μg, fentanyl 12.5–25 μg, or sufentanil 5–10 μg [27, 35]. It is imperative to consider that the operative time could be longer than the surgeon’s estimate since there are many “dead times” that prolong the total time required to complete the surgery. Table 9 shows the possibilities of mixtures of local anesthetic plus adjuvants according to the expected surgical times. Note that the possibility of 1-hour surgeries is included, which is rare in this field: scar reviews, small areas of liposuction, perineal plasties, etc. The combination of procaine + clonidine + fentanyl is excellent. Low doses of local anesthetic of the family pipecoloxylidide (PPX) (bupivacaine, mepivacaine, ropivacaine, and levobupivacaine) are good but usually last longer, and in a very busy environment, they could prolong the time of home discharge. For surgeries lasting up to 2 hours, local anesthetic PPX in low doses and added adjuvant drugs are an ideal combination.
Approximate duration | Drugs and recommended doses | Observations |
---|---|---|
Surgery up to 1 hour | Lidocaine 30–100 mg | The use of lidocaine tends to disappear due to the possibility of local neurotoxicity |
Lidocaine 30–50 mg + clonidine 75 μg | ||
Lidocaine 30–50 mg + fentanyl 25 μg | ||
Bupivacaine 5–7.5 mg + clonidine 75 μg or fentanyl 25 μg | Local anesthetics of the PPX family used in low doses tend to replace the use of lidocaine in brief procedures | |
Levobupivacaine 5–7.5 mg + clonidine 75 μg or fentanyl 25 μg | ||
Ropivacaine 7.5–10 mg + clonidine 75 μg or fentanyl 25 μg | ||
Procaine 100–200 mg + clonidine 75 μg or fentanyl 25 μg | Its short duration improves with the addition of adjuvants | |
Surgery from 1 to 2 hours | Bupivacaine 10–15 mg + clonidine 150 μg and/or fentanyl 25 μg | The duration of the average doses of PPX local anesthetics is prolonged with the addition of clonidine in a dose-dependent manner |
Levobupivacaine 10–15 + clonidine 150 μg and/or fentanyl 25 μg | ||
Ropivacaine 15–20 + clonidine 75 μg and/or fentanyl 25 μg | ||
Surgery greater than 2 hours | Bupivacaine 15–20 mg + clonidine 150–300 μg and/or fentanyl 25 μg | High doses of clonidine favor spinal anesthesia that can reach 3–5 hours of surgical anesthesia, with excellent postoperative analgesia |
Levobupivacaine 15–20 mg + clonidine 150–300 μg, and/or fentanyl 25 μg | ||
Ropivacaine 20–30 mg + clonidine 150–300 μg and/or fentanyl 25 μg |
Local anesthetics and coadjuvant drugs in spinal anesthesia [20].
The local hyperbaric anesthetics have an ampler intrathecal cephalic diffusion than the isobaric ones, which is useful in the operative procedures in high dermatomes (upper abdomen and thorax). On the other hand, isobaric local anesthetics are better in the pelvis and lower extremities. Opioids, especially fentanyl, improve the quality of anesthesia without affecting recovery.
Subarachnoid anesthesia in plastic surgery procedures can be done with a single injection, with or without adjuvant drugs, usual doses, low doses or high doses, or combined with extradural anesthesia. The single injection with spinal anesthesia with mono-dose is an easy, safe, and economic technique that produces a deep anesthetic and motor block, with a low incidence of failure and undesirable side effects. It is the procedure most used in short- and medium-length surgeries, being able to be used in some prolonged procedures such as abdominoplasties with or without breast surgery. It is recommended to use small spinal needles G26, G27, and G29, with blunt tip, cutting tip, or special cutting tip. Low doses of long-acting local anesthetics play an important role in outpatients [27, 28]. A comparative study with 6 mg of hypobaric bupivacaine (0.5% in 1.2 mL) versus 6.1 mg of almost hypobaric bupivacaine (0.18% in 3.4 mL) had similar effects on the anesthetic level, duration of sensory, and motor block [36]. Dosage of 6 mg of bupivacaine versus 7.5 mg of bupivacaine [37], both doses added with 25 μg of fentanyl, has similar results in terms of diffusion, duration, and regression of the sensory block. Doses between 5 and 8 mg of ropivacaine, levobupivacaine, or bupivacaine provide up to 150 minutes of intrathecal anesthesia, enough time for most outpatient procedures in cosmetic surgery, time that can be prolonged with the addition of 150–300 μg of spinal clonidine up to 3–5 hours. The most used doses vary from 10 to 15 mg of hyperbaric bupivacaine, being possible to increase these doses up to 20–25 mg in special cases. Drowsiness, bradycardia, and hypotension of easy control are the most frequent effects.
|
|
General contraindications for neuraxial anesthesia.
Without pretending to exhaust the topic, this section reviews the usual anesthesia techniques for most common procedures in plastic surgery: breast implants, liposuction, abdominoplasty, rhytidoplasty, combined cosmetic surgeries, and fat transfer.
Breast implant surgery occupies the first place among cosmetic surgery procedures in the USA, and it is likely that the same happens in other countries. Most patients are healthy, but there are some cases of women with breast reconstruction and implants who have a history of surgery for breast cancer. Several anesthesia techniques have been described for this procedure such as general inhaled or intravenous anesthesia, cervicothoracic epidural block, intercostal blocks, facial plane blocks, and tumescent injection with lidocaine. The advantage of regional techniques is that it produces less nausea, vomiting, postoperative pain, and has a lower cost [41, 42]. Cervicothoracic epidural block with approach in C7–T1 and T3–T4, with lidocaine 1%, ropivacaine 0.75%, bupivacaine 0.5%, or levobupivacaine 0.5% (8–12 mL), produces enough anesthesia with better postoperative analgesia than general anesthesia. A single dose of one of the mentioned local anesthetics is adequate in most cases, and when required, a second epidural dose must be injected through the epidural catheter. Epinephrine 1:80,000 can be added (except when ropivacaine is used) to prolong duration of local anesthetics. The most common side effects include transient elevation of blood pressure with tachycardia, tremor, nasal congestion, and nausea. Hypotension and difficulty breathing are rare [42]. It is also possible to use paravertebral or intercostal nerve blocks. Since Blanco et al. described ultrasound-guided interfacial plane blocks for postoperative breast analgesia; modifications to the initial technique have been published [43, 44, 45]. Interfacial blocks score over traditional regional anesthetic procedures as they have no risk of sympathetic blockade, intrathecal or epidural spread which may lead to hemodynamic instability, and prolonged hospital stay [44]. These blocks are not an alternative to general anesthesia, epidural anesthesia, or paravertebral blocks since they do not produce adequate regional surgical anesthesia. However, they can be supplemented with intravenous sedation techniques, general anesthesia, or neuraxial anesthesia. Postoperative pain not only involves the breasts; it can extend to the sternum, lateral aspect of the thorax, armpits, and middle back, being more severe when the implants are submuscular. Postoperative pain can be managed with NSAIDs such as parecoxib, ibuprofen, ketoprofen, ketorolac, or diclofenac combined with low doses of opioids. Tramadol is recommended because of its dual mechanism of analgesic action. Methocarbamol can be associated with the previous scheme. Some investigators have found adequate analgesia with the continuous or intermittent administration of local anesthetics through catheters implanted during surgery [46, 47]. It has not been defined if paravertebral blocks decrease the incidence of chronic postoperative pain in breast surgery [48].
The evaluation of candidates for abdominal contour surgery allows patients to be classified according to the possibilities of surgery taking in consideration the skin, fat, and muscles. This group includes liposuction, abdominoplasty, abdominal muscle repair, and various combinations that lengthen the operative time such as a 360° liposuction and mommy makeover.
Plasticine model made by the patient to accurately show us the shape and size that she wants for her buttocks.
There are two types of liposuction: the dry technique and the tumescent one. The latter is defined as the removal of subcutaneous fat under anesthesia infiltrated with large volumes of saline solution added with epinephrine and a local anesthetic, usually lidocaine. The original definition excludes the use of another type of anesthesia, whether it is neuraxial or general, as well as the fact that it is done without the presence of an anesthesiologist. However, currently this type of liposuction is frequently done with epidural block, with spinal anesthesia, or with general anesthesia, in addition to infiltration with Klein’s solution (50 mL of 1% lidocaine solution (500 mg), 1 mL of 1:1000 epinephrine (1 mg), 1000 mL of 0.9% saline, and 12.5 mL of 8.4% NaH2CO3 solution (12.5 mEq)) [50]. This type of anesthesia involves a dose of lidocaine 35–55 mg/kg of body weight and added epinephrine to achieve concentrations of 0.25–1.5 mg/L, without exceeding total adrenaline total dose of 50 μg/kg. These high doses make it obligatory to perform these procedures in surgery rooms that have all the facilities for monitoring, cardiac resuscitation, ventilatory support, and, always, recovery area under the care of an anesthesiologist. It is an apparently low-risk procedure, which can be complicated by systemic toxicity from local anesthetics, hypothermia, fat embolism, electrolyte imbalances with fluid overload, and/or acute anemia [51, 52]. One of the limitations during cosmetic surgery, especially during tumescent liposuction, is the total dose of the local anesthetic. For this reason, it is advisable not to combine liposuction with other procedures that require the injection of local anesthetics as the maximum dose of these drugs can be exceeded. There is no informed agreement in the literature on what is the top dose of lidocaine; the literature written by dermatologists and plastic surgeons mentioned 55 mg/kg of weight [50, 52, 53, 54], whereas the literature that comes from investigations carried out by anesthesiologists mentions 5 mg/kg of weight. In Europe, it is considered safe to use a total of 200 mg of lidocaine without epinephrine, and up to 300 mg is allowed in the United States of America. When epinephrine is added, the lidocaine dose in both regions is 500 mg. Epinephrine 1:200,000 reduces absorption of subcutaneous lidocaine by 50% and intercostal, epidural, and brachial in 20–30% [55]. PPX local anesthetics should never be used in tumescent liposuction. There is no agreement on the best anesthetic technique for liposuction, whether it is the modality under local anesthesia with the Klein solution or with general anesthesia or neuraxial block. With both procedures deaths have been reported [49, 56, 57], and the reports are not completely reliable.
The total volume of fat removed should not exceed 5 L in a single intervention or not be greater than 5% of body weight [58, 59]. Higher volumes increase the risk of complications, especially hypovolemia due to bleeding and acute hydro-electrolytic alterations. Another topic of interest in the management of these patients is the replacement of fluids during the trans-anesthetic period; Trott et al. [60] recommended the following scheme: (a) liposuction of small volumes (<4 L of aspirate) = maintenance liquids + the volume of the injected subcutaneous solution and (b) liposuction of large volumes (aspirated ≥4 L) = maintenance liquids + the volume of the solution injected +0.25 mL intravenous crystalloids per mL of aspirate extracted after 4 L. These authors emphasize that this fluid replacement guide does not replace a good clinical criterion and communication between the surgeon and the anesthesiologist is always fundamental. The goal is to maintain a normal intravascular volume with a postanesthetic hematocrit above 30% and albumin levels above 3 g.
The so-called 360° liposuction has become fashionable. It is a procedure that combines liposuction of the entire truncal midsection to accomplish a complete curvier contour figure from every angle. It can be combined with dermolipectomy, with plication of the rectus abdominis muscle, and with or without umbilicoplasty or gluteal fat grafting [61, 62].
In our opinion, general anesthesia should be avoided and reserved for very select, complex cases or for patients who cannot tolerate or cooperate with conscious sedation [6]. The selection is indistinct and must be based on the physical conditions of the patient. In Lotus Med Group, we use isoflurane, sevoflurane, or desflurane and avoid or minimize the use of muscle relaxants. When the patient is extubated, special attention should be paid to avoid coughing and bowing that may facilitate bleeding in the surgical site.
Acute postoperative pain is an unresolved issue, including plastic surgery patients. Most plastic surgery procedures are accompanied by moderate/intense postoperative pain that can be disabling and prolong the hospital stay. The multiple neural ending injuries in liposuction and tummy tuck, even muscle elongations during breast implants, are just some examples that make it necessary to plan a rational analgesic scheme. The ideal analgesia should start from the pre-anesthetic phase using preemptive and preventing drugs. The combined use of opioids with NSAIDs is the cornerstone in the prevention and management of pain after plastic surgery. The controversy not clarified about the utility versus the negative effects of cyclooxygenase inhibitors has favored multiple investigations whose results allow the safe use of these drugs. Celecoxib 400 mg preoperatively followed by 200 mg every 12 hours reduces pain; total dose of opioids facilitates early recovery [70]. Parecoxib 40 mg i.v. every 12 hours is effective, and when methylprednisolone 125 mg intravenously is associated before surgery, it significantly reduces emesis [71]. This combination also reduces postoperative fatigue. The combination of tramadol with ketorolac is part of our routine, being able to replace acetaminophen with codeine. Mild pain can be treated with acetaminophen-codeine or sodium metamizole (dipyrone). Pregabalin and gabapentin may have a preventive analgesic effect. Sener et al. [72] found that in patients of septorhinoplasty lornoxicam (25 mg/day) has better tolerability and postoperative analgesia than dipyrone (5 mg/day) administered with a system of analgesia i.v. controlled by the patient. Gabapentinoids (gabapentin, pregabalin) and ketamine have additive or synergistic effects that decrease the doses of anesthetics in the transoperative and opioids in the immediate postoperative period.
Although the analgesic mechanism of esmolol (ultrashort-acting cardio-selective β1-adrenergic receptor antagonist) is not well known [73], some clinical studies have resulted in a decrease in propofol during the induction of general anesthesia, a reduction of general anesthetics during maintenance, and a reduced dose of transoperative opioids, as well as it reduces immediate postoperative pain [74, 75, 76]. Its use in rhinoplasty seems to reduce the dose of opioids in the intraoperative period and the intensity of immediate postoperative pain [77, 78].
Regional analgesia, as mentioned before, has a very important role: local anesthesia infiltrations and interfacial, paravertebral, intercostal, or epidural blocks.
Outpatient or short-stay plastic surgery patients should observe home discharge criteria that have been established for other types of surgery. These basic criteria establish the home discharge of patients in a safe manner and avoid readmissions due to complications. Uncontrolled pain, nausea, vomiting, and urinary retention are examples of frequent readmission to the surgical unit or hospital. In some patients it is not necessary to meet 100% of these discharge criteria, but they should be warned of the natural evolution of the gradual disappearance of the side effects of anesthesia and facilitate telephone communication with the surgical unit, the surgeon, and the anesthesiologist. They require appropriate postanesthetic and postsurgical indications, transportation, and occasional professional company. Each ambulatory surgery unit/hospital must have its own discharge criteria, in accordance with the published guidelines and with its own characteristics and needs of their patients: from simple scales to more elaborate procedures such as the new Postoperative Quality Recovery Scale (PQRS) assessment that evaluates six areas: physiological, nociceptive, emotional, daily activities, cognition, and general patient perspective [79]. Table 11 shows the usual discharge home criteria. The proper information on the patient evolution at the recovery house or patient home favors the prevention and the opportune diagnosis of complications [80].
Hemodynamic stability | The return of vital signs to pre-anesthetic figures is mandatory |
---|---|
Alertness | Patient awake, well oriented. Spinal anesthesia favors this state of alert which facilitates optimal home discharges |
Permeable oral route | Tolerate the intake of liquids or solids without nausea or vomiting |
Analgesia | Controlled postoperative pain (EVA <2/10) with oral analgesics. Subarachnoid anesthesia with adjuvants provides a prolonged period of analgesia that facilitates early home discharge and reduces the dose of analgesics. It is convenient to prescribe a combination of opioid and non-opioid analgesics according to the expected postoperative pain and the profile of each patient |
Spontaneous micturition | This is a controversial requirement. Some centers consider it as mandatory to avoid readmissions by bladder balloon. In our practice we do not consider this requirement as indispensable, and the patient is informed of the remote possibility of difficulty urinating. We avoid the use of intrathecal morphine to reduce this risk |
Ambulation | Complete regression of the motor block is convenient. The patient can try to walk when he/she has recovered the perianal sensitivity and can flex and extend the foot. In some cases, it is feasible to discharge without 100% recovery |
Headache | Although the classic CPPD is presented as of the second post-block day, there are patients who can develop it in the immediate postoperative period. It is prudent to investigate it with the patient semi-seated or standing |
Other | Absence of bleeding at the operative site, ensure company, stay and transport to patients who do not drive, establish possible means of communication such as telephone, FAX, email |
Criteria for home discharge.
Medical ethics and government regulations emphasize excellent care and safeguard the health needs of patients. The correct and sensitive communication of this carefulness is essential for a correct anesthesiological care. The lesions associated with anesthesia are a frequent cause of morbidity and litigation, so it is mandatory to identify the common factors associated with peri-anesthetic injuries and thus reduces possible demands. In anesthesia for plastic surgery, as in other surgical procedures, cardiopulmonary events are the most common errors or incidents that cause severe neurological damage or death. The keys to prevent legal action against the anesthesiologist are simple acts such as establishing an adequate relationship with the patient and his family from the pre-anesthetic period, appropriate pre-anesthetic evaluation, filling out the informed consent, always using the correct monitoring, performing the best anesthesia, and postanesthetic care [14].
The complications in plastic surgery are due to four general factors: (a) characteristics of the establishment where the procedure is performed, (b) type of surgery and surgeon, (c) physical condition of the patient, and (d) quality of anesthesiological care. The study by Clayman and Caffe [81] conducted in Florida, USA, with deceased patients who had been operated in office-based surgery facilities found 36 deaths in 5 years, 18 related to plastic surgery, 3 of which were seen by non-plastic surgeons, and 12 under general anesthesia, 10 of which were administered by anesthesiologists and 2 by nurse anesthetists. Seven of these cases died before discharge and 11 after apparent appropriate discharge. The deaths that occurred before patients were discharged from hospital were due to bronchospasm, deep sedation, one related to illicit drug use, and the other to fatty embolism. Of the 11 patients discharged, seven died due to possible thromboembolism. In the rest, the cause of death was not determined. Most of these deaths could be avoided with simple measures such as adequate trans-anesthetic surveillance, prophylaxis of DVT/PE, and optimal patient selection.
Chapter 7 of this book discusses the most frequent and unusual complications of anesthesia and plastic surgery.
The challenges in anesthesia for plastic surgery patients are multiple since it is about people with perfectionist ideas that seek to improve their self-esteem through showing a better figure. This special personality makes them to search for a surgical medical team that guarantees their idealized success, which is based on information lacking scientific basis. On the other hand, the increasing sites offering plastic surgery has favored a demand not only for quality but also for more accessible prices. This nonmedical challenge is combined with the challenges of anesthesiological care in healthy patients, in apparently normal cases, and in people with systemic comorbidities. Each of these groups always requires a scrupulous comprehensive preoperative medical assessment and the development of a modifiable anesthetic plan. Another problem is the short and mediate term follow-up of these patients, since one way to improve our anesthesiological techniques is to study the evolution outside the operating room. The anesthesiologist rarely can see this type of outpatient or short-stay patient. So, it is prudent to establish a means of communication from the time of the pre-anesthetic visit to a long postanesthesia period. The Internet is by far the most viable way to determine what kind of evolution each of these patients have, especially the study of complications.
Patient-tourists represent a significant challenge very little studied in plastic surgery. They are people who have traveled for several hours or days, who come from other countries and who usually have not had a surgical or pre-anesthetic evaluation. They must be evaluated quickly and correctly to determine their viability to the procedures they want. It is common to see uncommon pathologies that do not contraindicate anesthesia, but can influence perioperative pharmacological management [2, 89].
Ambulatory and short-stay plastic surgery is growing logarithmically around the world. Anesthesiologists are more often subjected to the challenge of providing anesthesia to these patients, who on the other hand are scheduled every day for longer procedures and high risks that previously disqualified them for outpatient procedures. To favor an adequate outcome in this group of ambulatory patients—healthy and not so healthy, anesthesiologists should be oriented to the rational use of short and intermediate action drugs, with the goal of reducing morbidity and mortality. Techniques to prevent pain, nausea and vomiting, and early ambulation will be the most accepted procedures. The anesthetic techniques for outpatient surgery differ greatly from the procedures for short-stay patients, since the latter are scheduled to remain hospitalized for a minimum of 24 hours, unlike outpatient in which to prolong their stay beyond 5 pm can be considered as a failure in the anesthetic plan. A short recovery time after anesthesia is very important for the patient, his doctors, and the surgical unit.
Plastic surgery performed in ambulatory surgery units has some potential benefits such as ease of programming, reduced costs, and comfort for the patient and surgical staff. On the other hand, the inconveniences of ambulatory anesthesia should be considered, such as nausea and vomiting, uncontrolled postoperative pain, unplanned hospitalization, and, finally, occasional death. The latter is the most feared and should not happen.
Ambulatory cosmetic surgeries can potentially be managed with any anesthesiological technique. Although most anesthesiologists use general anesthesia for these procedures, regional anesthesia techniques have shown certain advantages such as better pain control, attenuation of the response to operative stress, preserving perioperative immune function, better preservation of oxygenation and lung residual functional capacity, improvement of visceral vascular flow, early recovery of postoperative ileus, and reduction of venous thrombotic disease and pulmonary embolism.
We thank the images of www.anestesia-dolor.org for allowing us to publish it.
None.
Multiple pregnancies are the result of one of the three possibilities: a fertilization of two or more oocytes from different spermatozoids, a single fertilization followed by a splitting of the zygote, or a combination of both [1]. These pregnancies have an increased risk of several complications for both mother and fetuses, such as diabetes mellitus, hypertensive disorders associated with pregnancy, preeclampsia, anemia, hyperemesis, hemorrhage, and cesarean delivery [2, 3, 4, 5] in the maternal side and higher risk of fetal anomalies, fetal demise, neonatal death [6], and preterm birth in the fetal side [7].
It is known that monochorionic (MC) pregnancies have higher rates of fetal morbidity and mortality when compared to dichorionic (DC) ones [1, 8, 9]. Besides that, the MC pregnancies have specific complications such as the twin to twin transfusion syndrome (TTTS), the selective fetal growth restriction (sFGR), the twin anemia polycythemia sequence (TAPS), and the twin reversed arterial perfusion sequence (TRAPS). Most of these complications can be managed and treated in order to decrease the fetal morbimortality.
In the last years, the rate of multiple pregnancies has raised all over the globe. In the USA, it rose from 18.9in 1980 to 33.4 twins per 1000 births in 2016. The twin birth rates were higher in black women, followed by non-Hispanic white women. The triplet and high-order multiple birth rate has decreased about 48% in the last 8 years, from 193.5 in 1998 to 101.4 twins per 100.000 births in 2016 [7]. This decrease in high-order multiple pregnancies illustrates the reproductive medicine societies’ strategies for reducing the risk of high-order pregnancies, like single-embryo transfer and multifetal pregnancy reduction [10, 11, 12].
In England, there is also an increase in multiple births. From 1998 to 2016, the multiple maternity rate rose from 14.4 to 15.9 twins per 1000 births. Since 1993, women aged 45 and over have consistently recorded the highest multiple maternity rate. These changes in the multiple pregnancy rates are due to the increase in ART. It is estimated that in vitro fertilization (IVF) conceptions are 11 times more likely to result in a multiple birth than natural conceptions. In 2014, 16% of IVF pregnancies resulted in multiple birth, with nearly 19,000 IVF babies born in the UK in 2014 [13].
This trend was largely attributed to an elevated amount of dizygotic pregnancies, without significant variations in monozygotic births over the past few decades. The dizygotic twinning rate is affected by many factors such as race, previous multiple pregnancy, maternal age and parity, lifestyle, season, use of fertility drugs and treatments, genetics, and others [14, 15, 16].
The high number of multiple births impacts directly in rate of preterm birth and low birthweight. Data from 2016 show that among twin pregnancies, 59.9% are born before complete 37 weeks of gestation, while in singletons, only 8% are preterm births. In singleton births, 6.4% were born with weight less than 2500 g. This percentage is 55.4 in twins and more than 95% in triplets [7].
The MC pregnancies have several unique and serious complications that contribute to a perinatal mortality rate of 11% [17, 18]. The pathophysiology of most of these complications is related to the placental angio-architecture [19]. Placental anastomoses are described since the 1600s. The term “third circulation” that represents an “area of transfusion” and the potential harmful effect of vascular connections between the fetuses was first described by Schatz in 1896 [20]. In 1965, Naeye [21] identified the effect of chronic nutritional deprivation on the size of organs in one twin while appreciating that transfusion to the other increased the hemoglobin concentration and hematocrit, with subsequent cardiomyopathy and hypertension. Since then, several authors have proposed diagnosis criteria and different kinds of treatments of the MC pregnancy problems. In this session, the main complications of the MC gestations will be discussed.
One of the first suggestions of this disease in history lies in a Dutch painting from 1617 named the Early-Deceased Children of Jacob de Graeff and Aeltge Boelens that illustrates two children. One of them is pale and the other plethoric (Figure 1). Twin to twin transfusion syndrome is one of the main complications that occurs in about 10–15% of the MC pregnancies with an overall incidence of 3 in 10,000 pregnancies [22, 23].
The Dutch painting the Early-Deceased Children of Jacob de Graeff and Aeltge Boelens shows two male twins: one pale and the other plethoric.
If left untreated, TTTS mortality rates are about 70–100%. Perinatal mortality is the result of either miscarriage or very preterm delivery as a consequence of severe polyhydramnios and uterine distention or fetal demise due to severe cardiovascular disturbances [24, 25].
The pathophysiology underlies in the placental angio-architecture which is characterized by individual placental territory size, cord insertion location, and the quantity, size, and direction of intertwin anastomoses which are the most important factors in the pathogenesis because when unbalanced, they may cause hemodynamic changes that end in TTTS [26].
All MC placentas have intertwin anastomoses that are formed in the first trimester. They are important because they allow transfer of volume, red blood cells, vasoactive substances, and hormones. There are three type of intertwin anastomoses, and their flow may be unidirectional or bidirectional. Arteriovenous (AV) anastomoses are unidirectional but they exist in both directions (from donor to recipient or from recipient to donor). AV anastomoses end in a shared cotyledon where the arterial villous circulation of one twin links to the venous villous return of the other at the level of the intervillous space. Artery-to-artery (AA) and vein-to-vein (VV) are more superficial and bidirectional anastomoses (Figure 2). The flow direction depends on the types of connection, vessel calibers, and the pulse pressure. TTTS results from an unbalanced chronic perfusion from donor to recipient twin across placental anastomoses. This blood transfer is more likely in those placentas with more AV anastomoses and a lack of superficial balancing AA or VV anastomoses or when these bidirectional anastomoses are unusually small [26, 28].
Monochorionic placenta of not complicated twin pregnancy. The blue, white, and yellow arrows represent AA, VV, and AV anastomoses, respectively. Adapted from twin research and human genetics, Zhao et al. [
The principal clinical feature in TTTS is hypervolemia in the recipient and hypovolemia in the donor twin that may progress to cardiovascular impairment, hydrops, and fetal death. In the first trimester, diagnosis is difficult, since the amniotic fluid is usually normal in both fetuses. Some sonographic markers such as discordance in nuchal translucency thickness (NT) and abnormalities in ductus venosus (DV) may be early signs of TTTS, but they have a low predictive value [29, 30, 31]. The sonographic manifestations usually may be noted as early as 16 weeks of gestation, but they can appear in the third trimester as well. TTTS manifestations are rare after 28 weeks of gestation.
In the second trimester, the oligohydramnios in the donor twin, as well as the polyhydramnios in the recipient twin, can easily be noted by ultrasound examination. The donor becomes hypovolemic; therefore, renal perfusion decreases. This hypoperfusion activates the renin-angiotensin system (RAS), producing vasoconstriction, oliguria, and oligohydramnios. As the disease progresses, the fetus becomes anuric and gets “stuck” against the uterine walls (Figure 3). The circulation becomes hyperdynamic with an increased vascular resistance in the fetus and in the placenta, leading to fetal growth restriction (FGR), cerebral redistribution, and abnormal arterial Doppler assessment. The recipient twin becomes hypervolemic and, by myocardial stretching, releases atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), which are also biomarkers associated with heart failure. Elevated levels of these biomarkers and troponin are found in the amniotic fluid of the recipient, suggesting the presence of myocardial damage [26, 32, 33]. Despite the hypervolemia, vascular resistance in the recipient twin is increased. This hypertension is attributed to vasoactive mediators such as endothelin and also a paradoxically high level of renin. The source of endothelin and renin is probably partly from the placenta and partly from the donor via the vascular communications [34, 35]. These changes in fetal hemodynamics may cause a progressive cardiomyopathy that increases the heart size, reduces the myocardial compliance, and causes atrioventricular valvar regurgitation and abnormal venous Doppler findings. Several studies show that in early Quintero stages or even before the diagnostic of TTTS, the cardiac function in the recipient twin may be impaired [36, 37, 38]. A recent study noted that in the recipient twin, left ventricular filling pressures are elevated and systolic function is decreased before abnormalities in the right heart become apparent. They also described an improvement after fetoscopic laser photocoagulation (FLPC) in these fetuses [38].
Two fetal abdomens. The smaller one (short arrow) is stuck in the anterior uterine wall and has no amniotic fluid. The bigger fetus (long arrow) has polyhydramnios. Adapted from:
In the third trimester, fetal discordance in amniotic fluid and growth may occur, increasing uterine distension and causing shortened cervical length and preterm birth. Also, the mirror syndrome, a rare condition that presents itself as a sudden maternal edema, loss of renal and cardiac function, hypertension, and fetal hydrops, may appear in women with TTTS [26, 39, 40].
There is another rare form of TTTS described as “acute peripartum TTTS” which is defined as the intertwin hemoglobin difference at birth >8 g/dl. Since it is a rare condition (2.5% of all the MC pregnancies), there are a few studies and the pathogenesis remains unclear. Some studies says that in theory, acute fetal blood loss from the donor twin into the circulation of the recipient twin may occur as a result of variations in blood pressure due to uterine contractions or fetal positions [41].
In the past, TTTS was diagnosed at the time of birth based on neonatal criteria that included a growth discordance of 15–20% associated with discordant cord or neonatal hemoglobin concentrations of ≥5 g/dl [42]. In 1992, another study showed that these criteria are present in other conditions such as uteroplacental insufficiency, infection, and malformations and therefore should not be used as diagnostic criteria for TTTS [43].
The screening for TTTS should begin with an early ultrasound in order to confirm the chorionicity. The first trimester scan should be performed to look for morphology abnormalities and discordance in the NT measurement, abnormalities in the DV, and even crown-rump length discordances [44]. Unlike dichorionic pregnancies, where ultrasound can be performed every 4 weeks until the end of the second trimester, monochorionic pregnancies should be examined by ultrasound every 2 weeks beginning in the 16th week. An analysis of fetal growth, amniotic fluid deepest vertical pocket (DVP), umbilical artery pulsatility index (UA-PI), medium cerebral artery pulsatility index (MCA-PI), and peak systolic velocity (MCA-PSV) should be obtained [45, 46]. Besides that, a fetal echocardiography should be performed, since cardiac abnormalities are the most common defect in MC pregnancies. The fetal growth and the MCA-PSV are important parameters in the differential diagnosis of sFGR and TAPS, respectively. The early diagnosis is extremely important, since it allows timely treatment with FLPC.
In 1999, Quintero et al. standardized the diagnostic criteria and classification system of TTTS (Table 1) [47]. The diagnosis is made when a discordance in the DVP of the twins is visualized. The DVP of the donor twin should be <2 cm; meanwhile the DVP of the recipient, before 20 weeks, should be >8 cm, and after 20 weeks, it should be >10 cm in the European criteria and > 8 cm in the US criteria. The fetal bladders should also be evaluated since there might be a discordance in the size of the fetal bladders (larger in the recipient and smaller in the donor). It is worth reminding that weight discordance is not a diagnostic criterion for TTTS, but it also can be noted in the ultrasound examination.
Stage | Sonographic findings |
---|---|
I | DVP > 8 cm in the recipient* and < 2 cm in the donor twin |
II | Absent bladder filling in the donor |
III | Critically abnormal Doppler studies of either fetus** |
IV | Hydrops of either fetus |
V | Intrauterine fetal demise of either fetus |
TTTS staging system. Adapted from Journal of Perinatology, Quintero et al. [44].
Before 20 weeks the universal cutoff is 8 cm, and between 21 and 26 weeks, the cutoff is 8 cm in the USA and 10 cm in Europe.
Absent-reverse diastolic flow in the umbilical artery and/or absent/reverse flow in the ductus venosus or pulsatile flow in the umbilical vein.
There are some critics about it because this staging system is not progressive (e.g., stage I can go to stage IV without passing through stages II and III) [45], and it does not correlate well with survival chance in twins treated with FLPC [48]. Nevertheless, these criteria are the most used to classify TTTS.
The natural history of TTTS shows high rates of fetal morbidity and mortality. The perinatal death in some series of cases is about 70–100%, depending on the stage of disease [26]. In stage I, it is known that nearly 70% of the pregnancies remain stable or regress, but in 5% of cases of stages I or II, there is fetal death of one or both twins without warning. Besides that, only 30% of pregnancies managed expectantly have double survivors. In the other stages, mortality increases and treatment is necessary [49]. There are several ways to manage TTTS, which include FLPC, amnioreduction, selective reduction, and pregnancy termination.
The FLPC is the preferred option because its outcomes are better when compared to serial amnioreduction [50, 51]. For stage I, there is no consensus regarding the use of FLPC, so the cases should be individualized [52]. For stages II to IV, FLPC of placental anastomoses is the primary treatment between 16 and 26 weeks of gestation. In 2004, Senat et al. have shown that the mortality rate of fetuses treated with FLPC when compared with serial amnioreduction is significantly lower (RR 0.71; 95% CI 0.55; 0.92). This study also showed a decreased risk of intraventricular hemorrhage and neurological impairment in the laser group. Probably it is because there is a higher rate of prematurity in the amnioreduction group [51]. The procedure consists in inserting a fetoscope in the amniotic sac of the recipient, locating the donor twin and the intertwin membrane, coagulating (with Nd:YAG or diode laser) the intertwin anastomoses along the placental vascular equator, and, after that, removing amniotic fluid from the recipient sac [26, 51].
The quality of fetoscopy images in the early 1990s, when the first FLPC for TTTS was performed, was not good; therefore, the vascular anastomoses were not so easy to identify. The so-called nonselective technique for vessel coagulation was proposed [53]. This technique consisted in coagulating all of the vessels that crossed the intertwin membrane. It did not attempt to differentiate anastomotic from non-anastomotic vessels but rather to catch as many anastomoses as possible (Figure 4). With the development of new techniques and advance in fetoscopy technology, another approach was proposed: the selective fetoscopic laser photocoagulation (SFLP) [54, 55]. In this method, the vascular equator is visualized and only intertwin anastomoses are coagulated. This technique differs from the “nonselective” FLPC because the equator does not always coincide with the membrane; therefore, not all the vessels that cross the intertwin membrane should be coagulated; thus, theoretically, more placental tissue will be available for the donor twin after the procedure (Figure 4). In 2000, Quintero et al. compared the SFLP with the “nonselective” FLPC and found that the selective method yielded superior results, with survival of at least 1 infant in 83% of patients against 61% in the “nonselective” group [56]. The order of anastomoses coagulation was also studied. Some authors claim that the sequential method, which is a technique where the AV (donor to recipient) are coagulated before the VA, improves the survival rate of both fetuses [57, 58, 59] and the survival rate of at least on fetus [58, 59, 60]. A recent meta-analysis showed that there may be an improved double neonatal survival as well as a decreased donor and recipient fetal demise with the use of the sequential technique, although all the studies are small and underpowered to confirm the hypothesis [61]. Although the SFLP improved neonatal outcomes, there is about 18% of surgical failure, defined as postoperative symptomatic patent anastomoses (Figure 5) [62, 63, 64, 65], which could result in several complications such as recurrent TTTS (7–9%) [61, 65], TAPS (13–16%) [66, 67], and fetal death. This is a very delicate situation, because repeating the procedure is more difficult for several reasons such as the size of the uterus and the fetuses. Furthermore, it is associated with an overall perinatal survival rate of 50% [67].
Types of fetoscopic laser techniques in the treatment of TTTS. The nonselective method coagulates all vessels crossing the intertwin membrane. SFLP occlude anastomoses where they occur, sparing placental tissue of the donor. The equatorial laser dichorionization or Solomon technique separates the fetal circulations by coagulating the vascular equator. Adapted from Am J Perinatol. Benoit et al. [
Digitally modified image of placenta with recurrent TTTS with missed AV and VA anastomoses. Adapted from Am J Obstet Gynecol. Lewi et al. [
Recently, a new fetoscopic technique in which superficial coagulation of microvasculature on the chorionic plate between ablated anastomotic sites following SFLP was described [68] (Figure 4). Some authors compared the SFLP with this new technique in cohort studies and showed a trend toward the latter group [69, 70]. A subsequent randomized trial by Slaghekke et al. compared this new approach called the Solomon technique
The main early complications of laser photocoagulation are unintentional septostomy in 8–12%, premature rupture of membranes (PROM) in about 1–9%, and amnion dehiscence (membrane separation) in 5–10% of cases.
The time of delivery in cases of laser photocoagulation varies between 31 and 34 weeks and most of them (60–80%) are not elective. The most common indication is the onset of labor followed by nonreassuring fetal testing and PROM. The mode of delivery is usually by cesarean section, in 57–70% of cases [26, 51, 60, 69, 70].
Unfortunately, in low-income countries, the laser therapy is not widely known and there are no teaching facilities. One Brazilian study showed the initial experience of a single center and found a single twin and both twins’ survival rate 1 month after birth is 87.5 and 45.8%, respectively. These reported data are in line with those obtained in major centers worldwide, considering the learning curves and infrastructures [71]. In order to extend the range of the laser therapy to all the MC pregnancies, more teaching centers should be opened, and telemedicine should be used to aid low-income places to achieve the excellence in fetoscopy techniques.
The perinatal outcomes after the use of SFLP or Solomon technique are very satisfactory. Baschat et al. [70] found that the double survival rates at 6 months of age were 68% in the Solomon group and 50% in the SFLP. Ruano et al. [69] showed an overall neonatal survival rate from 61.8% in the SFLP group to 86.5% when Solomon technique was used. This difference could be due to the increased experience with fetoscopic laser in general and not to the use of the Solomon technique. In the only randomized trial, the single twin and both twins’ survival rates after 1 month in the SFLP were 87% and 60%, while in the Solomon group these rate were 85% and 64%, respectively [66].
The neurologic outcomes in the neonatal period following laser procedures, such as intraventricular hemorrhage, periventricular leukomalacia, cerebral white matter cysts, ventricular dilatation, and cerebral atrophy, range from 8 to 18% [51, 72, 73]. The long-term neurodevelopmental outcomes vary between 3 and 12% for cerebral palsy and 4 and 18% for neurodevelopmental impairment [73]. In one study, the neurodevelopmental scores in preterm-born children treated with laser therapy for TTTS were similar in preterm-born DC children, suggesting that prematurity has the main role in the neurologic impairment in fetus treated with laser photocoagulation [74]. Other authors have suggested risk factors for poorer neurodevelopmental outcomes [75, 76]. Lopriore et al. analyzed 212 pregnancies treated with fetoscopic laser surgery and found that advanced gestational age at laser surgery, low gestational age at birth, low birthweight, and high Quintero stage are risk factors of poor neurological development at 2 years of age [76].
Several studies report a rapid cardiac function recovery in the recipient and in the donor twin [36, 38, 77, 78, 79, 80]. The coagulation of vascular anastomoses stops the volume exchange, as well as the vasoactive mediators, allowing cardiac output, cardiac size, valvular regurgitation, and ventricular inflow to normalize in the recipient twin in about half of the cases [38, 77]. The donor twin shows an increase in left ventricular filling pressure and cardiac output, which can temporarily cause a relative volume overload. It can worsen the cardiac function and cause ductus venosus alterations and even hydrops; however, these changes tend to disappear by 2 to 4 weeks after the laser procedure [79, 81, 82].
There are other types of treatment, such as septostomy. This procedure increases the risk of severe complications like cord entanglement and disruption of the membrane. This procedure has generally been abandoned [64, 83]. The selective reduction is another therapeutic option that tries to improve the outcome of the surviving twin whenever there is an imminent risk of spontaneous intrauterine death of one fetus. It can be performed either by ultrasound-guided vascular embolization or cord clamping through fetoscopy. A maximum of 50% survival is reached and most services have not supported this technique [68].
The fetoscopic laser coagulation is the gold standard treatment in stage II to stage IV TTTS affected pregnancies; the SFLP and Solomon technique are the best options for lowering the mortality and morbidity in theses fetuses. For Quintero stage I, there is not enough data that favors laser surgery, and more powered studies should be done comparing it to other kinds of treatment; therefore, the treatment for this stage has to be individualized.
Selective intrauterine growth restriction happens in 10–25% of MC gestations and it considerably increases perinatal morbidity and mortality [84, 85, 86]. The diagnostic criteria for sFGR differ among clinicians; therefore, it is hard to compare the findings of existing studies, to combine their results, or to establish robust evidence-based management. The pathophysiology in sFGR in MC and DC twins seems to be different. While DC sFGR have conventionally been managed as FGR in a singleton pregnancy, MC twin pregnancies sFGR is thought to result mainly from an unequal placental share. In most cases the origin is in the placental territory discrepancy (Figure 6). Vascular anastomoses between both fetuses intrinsically justify IUGR, and one twin receives better oxygenated blood [87].
Macroscopic photograph demonstrates the measurement of the vascular anastomoses. There is a 2-mm arterioarterial anastomosis (dashed arrow) and 5 AV anastomoses (arrows). A macroscopic placental surface discordance is also visible (green dashed line: Vascular equator). Adapted from Am J Obstet Gynecol. Lewi et al. [
Since many authors have proposed different diagnostic criteria, in 2017, the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) published a guideline for the sFGR diagnostic. It is defined as a condition in which one fetus has estimated fetal weight (EFW) < 10th centile and the intertwin EFW discordance is >25%. EFW discordance is calculated by the following formula: (weight of larger twin – weight of smaller twin) × 100)/weight of larger twin [45]. This weight discordance was proposed by an expert consensus, mainly based on data that show that an 18% EFW discordance reflects poorer outcomes both in DC and MC pregnancies [88]. Curiously, the charts used to monitor the fetal growth should be the same as those used in singleton pregnancies [45, 89], although specific multiple pregnancy charts are available [90]. However, there is a reduction in fetal growth in twin compared with singleton pregnancy, particularly in the third trimester. The key question for clinicians is whether this difference in growth represents adaptation or restriction [91]. Once the diagnosis is made, a detailed anomaly scan and screening for viral infections (cytomegalovirus, rubella, and toxoplasmosis) should be made. Amniocentesis may also be required to exclude chromosomal abnormalities as a cause of FGR [45, 92].
In order to follow up the sFGR pregnancies, as well as in singleton pregnancies, umbilical artery Doppler waveforms and UA-PI are accessed. In pregnancies complicated with sFGR, there are particularities in the umbilical artery Doppler probably because of the variability in the intertwin vascular anastomoses resistance [93, 94]. Three patterns are observed in the umbilical artery Doppler: positive end-diastolic flow, absent or reversed end-diastolic flow (AREDF), and intermittent absent or reversed end-diastolic flow (iAREDF) [95]. The latter pattern though is to result from the presence of transmitted waveforms from the larger into the smaller twin’s cord due to the existence of placental large AA anastomoses (Figure 6) [93, 94, 95]. Based on these three Doppler types, Gratacós et al. proposed a three-stage classification system of the sFGR fetuses. In stage I, the umbilical artery in the smaller twin has a positive end-diastolic flow; in stage II, there is an AREDF; and stage III is characterized by iAREDF (Figure 7) [95].
Classification of selective fetal growth restriction in monochorionic twin pregnancy. In type I, the umbilical artery Doppler waveform has positive end-diastolic flow, while in type II there is absent or reversed end-diastolic flow (AREDF). In type III there is a cyclical/intermittent pattern of AREDF. Extracted from ISUOG.
The stage I prognosis is better, with an overall intrauterine mortality rate of 3–4% and a 97% rate of intact survival-free from neurological complications according to two recent meta-analyses. The neonatal morbidity, defined as abnormal brain imaging, respiratory distress syndrome (RDS), admission to the neonatal intensive care unit (NICU), or retinopathy of prematurity (ROP), was reported in about 9% of newborns. The neurologic outcome in this stage seems to be better when compared to the others as well as the gestational age at delivery [84, 93, 94, 95, 97]. Stage II sFGR has a poorer prognostic. It is reported that these fetuses tend to have a high risk of hypoxic deterioration and consequently overall, single, and double intrauterine death rates of 16.6%, 8.2%, and 10.4% of cases managed expectantly [97] and a 21% perinatal mortality [84]. The double survival rate in this stage is about 25% [98]. The iAREDF pattern has an intrauterine mortality rate similar to stage II. The overall, single, and double intrauterine death occurred in 13.2%, 7.2%, and 5.5% of cases managed expectantly although this stage is more unpredictable than the others [86, 93, 95, 97, 98]. Some ultrasound markers can be used as adverse predictors such as ductus venosus Z score [98], velamentous cord insertion (Figure 8) [99, 100], and weight discordance. A recent meta-analysis found that, in MC twin pregnancies, excluding cases affected by twin to twin transfusion syndrome, twins with birthweight discordance ≥25% were at higher risk of intrauterine death (OR 3.2, 95%CI, 1.5–6.7) and neonatal death (OR 4.66, 95% CI, 1.8–12.4) compared with controls [101]. Gratacós et al. [93] found a 15% unexpected intrauterine death rate in the smaller twin on stage III sFGR compared with 2.6% and 0 in stages I and II, respectively. On the other hand, other authors show a better prognosis. Rustico et al. [102] showed a 0% rate in double fetal death at stage III as well as better rates in overall survival and lower neonatal death in the smaller twin (8% and 62%, respectively).
Monochorionic placenta with velamentous cord insertion in the smaller twin side. AV and VA anastomoses are seen and on big AA anastomoses. Adapted from Am J Obstet Gynecol. Lewi et al. [
When sFGR presents with an umbilical artery positive end-diastolic flow, the prognosis is good, and therefore it is a consensus that the expectant management based on a weekly fetal growth and UA-PI evaluation should be done to look for progression to more severe stages which can occur in up to 25% of cases. For stages II and III, several studies compared SFLP with cord occlusion or expectant management, but there are not powered studies to support a gold standard treatment. In a retrospective study with 142 stage II sFGR fetuses treated with SFLP, there was survival rate of the smaller, larger, and both twins of 38.7, 67.6, and 34.5%, respectively. The survival rate of at least one twin was 71.8% [103]. When compared to expectant management, SFLP for stage III sFGR showed a higher overall intrauterine death (14.5 vs. 36%, respectively) as well as a higher death rate in the smaller twin which is 19% for the expectant group and 66% for the SFLP group [104]. Other prospective trial with ten pregnant women with sFGR stages II or III and oligohydramnios treated with SFLP showed that only three newborns of the restricted group survived and all of the newborns in the larger twin group were well and alive at 28 days of age [105].
Cord occlusion of the smaller twin is an option for early diagnosed sFGR, when the spontaneous death of the restricted fetus is most likely to happen, but it is the most difficult decision for the parents to make since they give up the life of one child to protect the other. Chalouhi et al. [106] found a 90% survival rate in the larger twin after cord occlusion and a 4.5% neurologic complication rate which is much lower than the 26% rate when a spontaneous intrauterine death occurs [107].
The sFGR treatment is not yet defined. Several factors should be evaluated together with parents such as weight discordance, time of diagnosis (early vs. late), hemodynamic state of the restricted fetus at the time of diagnosis, and the will to protect the larger twin since the adverse outcomes are very low after a cord occlusion [94]. If FLPC or expectant management is elected, parent counseling should be made regarding complications and outcomes to both fetus.
The placental angio-architecture is responsible for most of the complications in MC pregnancies. The intertwin vascular anastomoses have a key role in the pathogenesis of TTTS and sFGR. In 2007, a new MC pregnancy complication was described by Lopriore et al. [108] that involves a discordance in postnatal hemoglobin and hematocrit levels, a difference in neonate reticulocyte levels, and small AV anastomoses in the placenta after colored dye injection (Figure 9). This condition was named twin anemia polycythemia sequence. TAPS happens when blood from one twin is slowly transfused to the other by small AV anastomoses at a 5–15 ml/ 24 h rate [108]. Unlike TTTS, there is a less acute and well-compensated intertwin transfusion process leading to a discordance in hemoglobin levels without hemodynamic or amniotic fluid alterations [110]. The reticulocyte levels are also increased in the donor newborn and decreased in the recipient, which differ from other acute diseases, such as acute peripartum TTTS [41]. Another characteristic of TAPS is that after colored dye injection in MC placentas after TAPS, AA anastomoses are observed in about 11% and all of them are small (<1 mm). In comparison, the incidence of AA anastomoses in uncomplicated MC pregnancies and TTTS pregnancies is 80 and 25%, respectively [111, 112], which suggests that AA anastomoses protect against TAPS and TTTS. The maternal side of the TAPS placenta also shows an important color difference. The donor side is more white than the recipient side that shows a plethoric aspect like the respective twin (Figure 10) [113].
TAPS placenta after colored dye injection (blue or green for arteries and pink or yellow for veins). The white arrows indicate the small AV and VA anastomoses. Adapted from placenta. de Villiers et al. [
Maternal side of the TAPS placenta showing the difference in color between the plethoric share of the recipient (left side of the placenta) and the anemic share of the donor (right side of the placenta). Adapted from twin research and human genetics. Tollenaar et al. [
TAPS may occur spontaneously or post-laser surgery. The prevalence of spontaneous TAPS is about 1.6–5% [18, 68, 114], while post-laser TAPS occurs in 3–16% [66], depending on the technique used. The possible pathophysiology for the latter is the inability to identify all AV anastomoses, therefore leaving some small AV anastomoses without coagulation. The Solomon trial showed a significant decrease in post-laser TAPS in the placental dichorionization group, supporting this hypothesis [66].
TAPS can be diagnosed either antenatally or postnatally. Antenatal diagnosis (Table 2) is based in MCA-PSV measurement in both fetuses showing an increased velocity in the anemic and a decreased velocity in the polycythemic twin. The most used criteria of TAPS diagnosis are an MCA-PSV > 1.5 MoM for the donor twin and <1.0 MoM for the recipient twin [111, 115]. Slaghekke et al. analyzed 43 twin pregnancies complicated by TAPS and found that a MCA-PSV > 1.5 MoM correlated with anemia (hemoglobin levels >5 SD below the mean) with a 94% sensitivity, a 74% specificity, a 76% positive predictive value, and a 94% negative predictive value. In the same study, MCA-PSV ≤ 1.0 MoM correlated with polycythemia (hemoglobin levels >5 SD above the mean) with a 97% sensitivity, a 96% specificity, a 93% positive predictive value, and a 99% negative predictive value [115]. In some TAPS cases, other ultrasound findings have been reported. The first one is the difference in placental thickness, and echodensity on ultrasound examination was detected [110]. Another ultrasound finding described in TAPS is the so-called starry sky liver [116] which is characterized by clearly identified portal venules and diminished parenchymal echogenicity. More studies are needed to further investigate the validity and significance of these antenatal ultrasound findings for the diagnosis of TAPS.
Antenatal criteria | Postnatal criteria |
---|---|
Donor MCA-PSV ≥ 1.5 MoM | Intertwin hemoglobin difference > 8 g/dl |
Recipient MCA-PSV ≤ 1.0 MoM | Reticulocyte count ratio > 1.7 |
Placenta with only small (diameter < 1 mm) vascular anastomoses |
Antenatal and postnatal diagnostic criteria for TAPS. Adapted from ultrasound Obstet Gynecol. Slaghekke et al. [111].
The postnatal criteria (Table 2) can be used when TAPS is not diagnosed by MCA Doppler. It is based on the finding of discordant hemoglobin levels (Hb difference > 8.0 g/dl) associated with an increased intertwin reticulocyte count ratio > 1.7 that is pathognomonic for TAPS and placental evidence of only small vascular anastomoses [111, 117].
The classification for TAPS was proposed by Slaghekke et al. in 2010 [111] based on the difference in hemoglobin levels postnatally (Table 3).
Antenatal stage | Doppler ultrasound |
---|---|
Stage I | MCA-PSV donor >1.5 MoM and MCA-PSV recipient <1.0 MoM, without other signs of fetal compromise |
Stage II | MCA-PSV donor >1.7 MoM and MCA-PSV recipient <0.8 MoM, without other signs of fetal compromise |
Stage III | As stage I or II, with cardiac compromise of donor, defined as critically abnormal flow* |
Stage IV | Hydrops of donor |
Stage V | Intrauterine demise of one or both fetuses preceded by TAPS |
Antenatal TAPS classification. Adapted from Ultrasound Obstet Gynecol. Slaghekke et al. [111].
Critically abnormal Doppler is defined as absent or reversed end-diastolic flow in umbilical artery, pulsatile flow in the umbilical vein, and increased pulsatility index or reversed flow in ductus venosus.
There is no optimal treatment for TAPS. Options include expectant management and early delivery; intrauterine transfusion (IUT) in the donor, with or without partial exchange transfusion (PET) in the recipient; selective feticide; and fetoscopic laser surgery.
Expectant management is made with closing ultrasound monitoring with serial MCA-PVS evaluation and an early delivery when necessary. It leads to a 75 to 83% survival rate [111, 118].
Another kind of treatment is IUT that can be performed intravascularly or intraperitoneal. It seems the latter may be superior to intravascular intrauterine transfusions because it is technically easier and can be performed as early as 15 weeks [119]. Although this method is commonly used, it is a palliative option, since it temporarily meliorates the donor anemia. Furthermore, the raise in blood viscosity in the recipient twin can lead to embolic complications [67]. These complications can be managed by partial exchange transfusion (PET) that decreases the viscosity of the blood of the polycythemic recipient. The perinatal survival rate in some studies is generally good, reaching 85–100% [111, 118].
The only causal treatment for both spontaneous and post-laser TAPS is laser surgery. It is technically more difficult because of the absence of polyhydramnios and a stuck twin, which makes the visualization of the vascular equator more challenging as well as the size of anastomoses, which is difficult to visualize during fetoscopy [111]. The results in small studies are satisfactory, with a survival rate of 94–100% [111, 118, 120, 121] and an apparent improvement in perinatal outcome by prolonging pregnancy and reducing respiratory distress syndrome [117].
The TAPS management should be made after evaluation of different factors, including TAPS stage, gestational age, and the clinician experience in the different types of treatments. In early stages, TAPS can be managed expectantly. If gestational age is below 26–28 weeks, laser treatment should be considered [113]. When laser treatment is not possible, IUT should be considered. When repeated IUT is expected or in case of severe polycythemia in the recipient, PET of the recipient can be done.
Twin reversed arterial perfusion sequence resulting in an acardiac twin is a rare condition and occurs in 1:35,000 births or 1% of all monozygotic twins [122]. It consists in one health twin (the “pump” twin) and one acardiac mass which is perfused by the other fetus’ heart. This acardiac twin most often has an underdeveloped head and upper body and impressive edema also mostly of the upper body. In some cases, there might be fetal movements. In rare cases, a rudimentary pulsating cardiac structure may be seen. It is though that the VV and AA bidirectional anastomoses are responsible for the perfusion of the acardiac fetus. One study analyzed the TRAPS placenta and found big AA anastomoses as well as veins in direct continuity with each other. They also noted that umbilical cords were attached, with insertion adjacent to each other [123]. The blood from the pump twin flows through the umbilical artery to the umbilical artery of the acardiac twin and then it flows back to the recipient twin through the umbilical vein. The returning blood bypasses the placenta and returns to the pump twin via VV anastomoses, without passing through the placenta. This condition may cause a hyperdynamic circulation and progressive high output cardiac failure in the pump twin causing fetal death in about half of cases if not treated [122, 124, 125].
The diagnostic is made by turning on the color Doppler and showing the inverse direction of blood flow in the aorta of the acardiac twin [92] (Figure 11). TRAPS is usually diagnosed in the 11–13 weeks scan or even in the early endovaginal ultrasound [126, 127, 128]. Given the fact that 50% of pump twin dies if expectant management is made and that in 33% of the TRAPS pregnancies diagnosed at the first trimester the healthy twin dies before 18 weeks [123, 129], several intrauterine interventions have been tested in order to improve the perinatal outcomes. The overall survival of the treatment methods is similar among several studies and varies between 71 and 86% [130, 131, 132, 133, 134]. The methods used to manage TRAPS are cord ligation; monopolar, bipolar, or laser cord coagulation; and fetoscopic laser coagulation of placental anastomoses. However, intrafetal techniques such as intrafetal laser ablation and intrafetal radiofrequency ablation (RFA) are preferred because, when compared to cord occlusion techniques, they are associated with a lower technical failure rate (13 vs. 35%), lower rate of preterm birth or rupture of membranes before 32 weeks (23 vs. 58%), and higher rate of clinical success (77 vs. 50%) [135].
Upper image: Acardiac twin with retrograde flow in the umbilical cord. Lower image: Normal recipient twin. Adapted from ultrasound Obstet Gynecol. Pagani et al. [
There are some doubts about the optimal time to do the treatment. Performing any procedure before the obliteration of the coelomic cavity increases the risk of talipes and miscarriage [136]; therefore, most of the authors perform the intervention between 13 and 16 weeks [124]. In one study in which the median gestational age at intervention (intrafetal laser ablation) was 13.2 weeks, there was a 41% mortality rate in the first 72 h after the procedure; therefore, surgery before 13 weeks of gestation should be avoided [136]. Some studies showed that expectant management could be offered in special cases. Jelin et al. [125] found a 100% survival when the acardiac twin had less than 50% of the pump twin’s weight. Other studies suggested that discordance between crown-rump length of the pump twin and upper pole-rump length of the TRAP twin could be potential predictors of pregnancy outcome [137].
The optimal approach should be an early diagnosis and a proper parental counseling and an intrafetal intervention, by laser or RFA in 13–16 weeks. The expectant management could be considered if the TRAP twin is smaller (about half the size) than the pump twin.
Monochorionic pregnancies are at a great risk of complications such as preterm birth, fetal and neonatal death, and neurological injury. The early sonographic screening is extremely important to diagnose some of the most important complications which can lead to death of one or both siblings. It should begin in the first trimester, where the confirmation of chorionicity should be done and the search for potential predictors of adverse outcomes such as NT discordance should be accessed. Some complications such as TRAPS can be diagnosed and managed in this period. Beginning in the 16th week, a biweekly detailed ultrasound examination is extremely important since it can detect early stages of TTTS, sFGR, and TAPS. Most of these complications can be treated in the mid-trimester improving the survival rate of one or both fetuses.
The fetoscopic approach is the main method to manage MC twin complications and should be available in specialized fetal medicine centers with trained staff to perform the laser surgery. Several laser techniques have been tested in the last years and the improvement in the outcomes is clear. Although the results are satisfactory, the complication rates, such as PROM and unintentional septostomy, are still relatively high as well as the both twins’ survival rate.
Future directions in the management of TTTS are likely to involve refinements in the prediction of the disease, clarification of the optimum frequency of surveillance, technique of laser therapy, prediction of adverse outcome after treatment, and development of other vascular ablative techniques.
Although the treatment efficacy is rapidly improving in big centers, in most parts of the world, there is a lack of specialized centers and trained personnel. In order to achieve an optimal management in MC pregnancy complications, it is important to improve the early screening and diagnosis and the referral system, mainly in low-income countries.
There are no conflicts of interest in this chapter.
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This response can be blunted with the appropriate mix of biocompatible materials and anticoagulation therapy. The use of anticoagulants, in turn, requires appropriate laboratory testing to determine whether the patient is appropriately anticoagulated. Physicians must balance the risks of bleeding with the risks of thrombosis; the proper interpretation of these tests is often shrouded in mystery. It is the purpose of this chapter to help demystify the coagulation system, anticoagulants, biocompatible surfaces, and coagulation testing so that ECMO practitioners can make informed decisions about their patients and to spur coordinated efforts for future research to improve our understanding of these complex processes.",book:{id:"5202",slug:"extracorporeal-membrane-oxygenation-advances-in-therapy",title:"Extracorporeal Membrane Oxygenation",fullTitle:"Extracorporeal Membrane Oxygenation - Advances in Therapy"},signatures:"Timothy M. Maul, M Patricia Massicotte and Peter D. 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In this chapter we discuss various cannulation techniques used.",book:{id:"5202",slug:"extracorporeal-membrane-oxygenation-advances-in-therapy",title:"Extracorporeal Membrane Oxygenation",fullTitle:"Extracorporeal Membrane Oxygenation - Advances in Therapy"},signatures:"Chand Ramaiah and Ashok Babu",authors:[{id:"183646",title:"Dr.",name:"Chand",middleName:null,surname:"Ramaiah",slug:"chand-ramaiah",fullName:"Chand Ramaiah"},{id:"189073",title:"Dr.",name:"Ashok",middleName:null,surname:"Babu",slug:"ashok-babu",fullName:"Ashok Babu"}]},{id:"27955",title:"Transfusion-Associated Bacterial Sepsis",slug:"transfusion-associated-sepsis",totalDownloads:8288,totalCrossrefCites:1,totalDimensionsCites:2,abstract:null,book:{id:"802",slug:"severe-sepsis-and-septic-shock-understanding-a-serious-killer",title:"Severe Sepsis and Septic Shock",fullTitle:"Severe Sepsis and Septic Shock - Understanding a Serious Killer"},signatures:"Jolanta Korsak",authors:[{id:"72828",title:"Prof.",name:"Jolanta",middleName:null,surname:"Korsak",slug:"jolanta-korsak",fullName:"Jolanta Korsak"}]},{id:"51211",title:"Triple Cannulation ECMO",slug:"triple-cannulation-ecmo",totalDownloads:4889,totalCrossrefCites:3,totalDimensionsCites:8,abstract:"Extracorporeal membrane oxygenation (ECMO) has emerged as an invaluable tool for bridging severe isolated or combined failure of lung and heart. Due to massive technical improvements, the application of ECMO is growing fast. While historically ECMO was initiated and maintained by cardiac surgeons, in recent times interventional cardiologists and intensive care specialists increasingly run ECMO systems independently with great success. Percutaneous ECMO circuits are usually set up in a dual cannulation mode, either as veno-venous or as veno-arterial configuration. A novel advanced strategy is the cannulation of three large vessels (triple cannulation), resulting in veno-veno-arterial or veno-arterio-venous cannulation. Both veno-venous and veno-arterio-venous cannulation may further be upgraded to veno-pulmonary-arterial or veno-arterial-pulmonary arterial cannulation, respectively. Triple cannulation expands the field of ECMO application but substantially increases the complexity of ECMO circuits. In this chapter, we review percutaneous dual and triple cannulation strategies, featuring a recently proposed unifying nomenclature. This unequivocal code universally applies to both dual and triple cannulation strategies (VV, VPa, VA, VVA, VAV, VAPa). The technical evolution of ECMO is growing fast, but it has to be noted that current knowledge of ECMO support is mainly based on observation. Thus controlled trials are urgently needed to prospectively evaluate different ECMO modes.",book:{id:"5202",slug:"extracorporeal-membrane-oxygenation-advances-in-therapy",title:"Extracorporeal Membrane Oxygenation",fullTitle:"Extracorporeal Membrane Oxygenation - Advances in Therapy"},signatures:"L. Christian Napp and Johann Bauersachs",authors:[{id:"180959",title:"Dr.",name:"L. Christian",middleName:null,surname:"Napp",slug:"l.-christian-napp",fullName:"L. 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He completed a one-year Post-Doctoral Fellowship awarded by the DFAIT (Foreign Affairs and International Trade Canada) at the Institute of Biomedical Engineering of the University of New Brunswick (Canada) in 2010. Currently, he is Professor in the Faculty of Electrical Engineering (UFU). He has authored and co-authored more than 200 peer-reviewed publications in Biomedical Engineering. He has been a researcher of The National Council for Scientific and Technological Development (CNPq-Brazil) since 2009. He has served as an ad-hoc consultant for CNPq, CAPES (Coordination for the Improvement of Higher Education Personnel), FINEP (Brazilian Innovation Agency), and other funding bodies on several occasions. He was the Secretary of the Brazilian Society of Biomedical Engineering (SBEB) from 2015 to 2016, President of SBEB (2017-2018) and Vice-President of SBEB (2019-2020). 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Prof. Sarfraz is also an editor-in-chief and editor of various international journals.",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"32650",title:"Prof.",name:"Lukas",middleName:"Willem",surname:"Snyman",slug:"lukas-snyman",fullName:"Lukas Snyman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/32650/images/4136_n.jpg",biography:"Lukas Willem Snyman received his basic education at primary and high schools in South Africa, Eastern Cape. He enrolled at today's Nelson Metropolitan University and graduated from this university with a BSc in Physics and Mathematics, B.Sc Honors in Physics, MSc in Semiconductor Physics, and a Ph.D. in Semiconductor Physics in 1987. After his studies, he chose an academic career and devoted his energy to the teaching of physics to first, second, and third-year students. After positions as a lecturer at the University of Port Elizabeth, he accepted a position as Associate Professor at the University of Pretoria, South Africa.\r\n\r\nIn 1992, he motivates the concept of 'television and computer-based education” as means to reach large student numbers with only the best of teaching expertise and publishes an article on the concept in the SA Journal of Higher Education of 1993 (and later in 2003). The University of Pretoria subsequently approved a series of test projects on the concept with outreach to Mamelodi and Eerste Rust in 1993. In 1994, the University established a 'Unit for Telematic Education ' as a support section for multiple faculties at the University of Pretoria. In subsequent years, the concept of 'telematic education” subsequently becomes well established in academic circles in South Africa, grew in popularity, and is adopted by many universities and colleges throughout South Africa as a medium of enhancing education and training, as a method to reaching out to far out communities, and as a means to enhance study from the home environment.\r\n\r\nProfessor Snyman in subsequent years pursued research in semiconductor physics, semiconductor devices, microelectronics, and optoelectronics.\r\n\r\nIn 2000 he joined the TUT as a full professor. Here served for a period as head of the Department of Electronic Engineering. Here he makes contributions to solar energy development, microwave and optoelectronic device development, silicon photonics, as well as contributions to new mobile telecommunication systems and network planning in SA.\r\n\r\nCurrently, he teaches electronics and telecommunications at the TUT to audiences ranging from first-year students to Ph.D. level.\r\n\r\nFor his research in the field of 'Silicon Photonics” since 1990, he has published (as author and co-author) about thirty internationally reviewed articles in scientific journals, contributed to more than forty international conferences, about 25 South African provisional patents (as inventor and co-inventor), 8 PCT international patent applications until now. Of these, two USA patents applications, two European Patents, two Korean patents, and ten SA patents have been granted. A further 4 USA patents, 5 European patents, 3 Korean patents, 3 Chinese patents, and 3 Japanese patents are currently under consideration.\r\n\r\nRecently he has also published an extensive scholarly chapter in an internet open access book on 'Integrating Microphotonic Systems and MOEMS into standard Silicon CMOS Integrated circuitry”.\r\n\r\nFurthermore, Professor Snyman recently steered a new initiative at the TUT by introducing a 'Laboratory for Innovative Electronic Systems ' at the Department of Electrical Engineering. The model of this laboratory or center is to primarily combine outputs as achieved by high-level research with lower-level system development and entrepreneurship in a technical university environment. Students are allocated to projects at different levels with PhDs and Master students allocated to the generation of new knowledge and new technologies, while students at the diploma and Baccalaureus level are allocated to electronic systems development with a direct and a near application for application in industry or the commercial and public sectors in South Africa.\r\n\r\nProfessor Snyman received the WIRSAM Award of 1983 and the WIRSAM Award in 1985 in South Africa for best research papers by a young scientist at two international conferences on electron microscopy in South Africa. He subsequently received the SA Microelectronics Award for the best dissertation emanating from studies executed at a South African university in the field of Physics and Microelectronics in South Africa in 1987. In October of 2011, Professor Snyman received the prestigious Institutional Award for 'Innovator of the Year” for 2010 at the Tshwane University of Technology, South Africa. This award was based on the number of patents recognized and granted by local and international institutions as well as for his contributions concerning innovation at the TUT.",institutionString:null,institution:{name:"University of South Africa",country:{name:"South Africa"}}},{id:"317279",title:"Mr.",name:"Ali",middleName:"Usama",surname:"Syed",slug:"ali-syed",fullName:"Ali Syed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/317279/images/16024_n.png",biography:"A creative, talented, and innovative young professional who is dedicated, well organized, and capable research fellow with two years of experience in graduate-level research, published in engineering journals and book, with related expertise in Bio-robotics, equally passionate about the aesthetics of the mechanical and electronic system, obtained expertise in the use of MS Office, MATLAB, SolidWorks, LabVIEW, Proteus, Fusion 360, having a grasp on python, C++ and assembly language, possess proven ability in acquiring research grants, previous appointments with social and educational societies with experience in administration, current affiliations with IEEE and Web of Science, a confident presenter at conferences and teacher in classrooms, able to explain complex information to audiences of all levels.",institutionString:null,institution:{name:"Air University",country:{name:"Pakistan"}}},{id:"75526",title:"Ph.D.",name:"Zihni Onur",middleName:null,surname:"Uygun",slug:"zihni-onur-uygun",fullName:"Zihni Onur Uygun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/75526/images/12_n.jpg",biography:"My undergraduate education and my Master of Science educations at Ege University and at Çanakkale Onsekiz Mart University have given me a firm foundation in Biochemistry, Analytical Chemistry, Biosensors, Bioelectronics, Physical Chemistry and Medicine. After obtaining my degree as a MSc in analytical chemistry, I started working as a research assistant in Ege University Medical Faculty in 2014. In parallel, I enrolled to the MSc program at the Department of Medical Biochemistry at Ege University to gain deeper knowledge on medical and biochemical sciences as well as clinical chemistry in 2014. In my PhD I deeply researched on biosensors and bioelectronics and finished in 2020. Now I have eleven SCI-Expanded Index published papers, 6 international book chapters, referee assignments for different SCIE journals, one international patent pending, several international awards, projects and bursaries. In parallel to my research assistant position at Ege University Medical Faculty, Department of Medical Biochemistry, in April 2016, I also founded a Start-Up Company (Denosens Biotechnology LTD) by the support of The Scientific and Technological Research Council of Turkey. Currently, I am also working as a CEO in Denosens Biotechnology. The main purposes of the company, which carries out R&D as a research center, are to develop new generation biosensors and sensors for both point-of-care diagnostics; such as glucose, lactate, cholesterol and cancer biomarker detections. My specific experimental and instrumental skills are Biochemistry, Biosensor, Analytical Chemistry, Electrochemistry, Mobile phone based point-of-care diagnostic device, POCTs and Patient interface designs, HPLC, Tandem Mass Spectrometry, Spectrophotometry, ELISA.",institutionString:null,institution:{name:"Ege University",country:{name:"Turkey"}}},{id:"267434",title:"Dr.",name:"Rohit",middleName:null,surname:"Raja",slug:"rohit-raja",fullName:"Rohit Raja",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/267434/images/system/267434.jpg",biography:"Dr. Rohit Raja received Ph.D. in Computer Science and Engineering from Dr. CVRAMAN University in 2016. His main research interest includes Face recognition and Identification, Digital Image Processing, Signal Processing, and Networking. Presently he is working as Associate Professor in IT Department, Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur (CG), India. He has authored several Journal and Conference Papers. He has good Academics & Research experience in various areas of CSE and IT. He has filed and successfully published 27 Patents. He has received many time invitations to be a Guest at IEEE Conferences. He has published 100 research papers in various International/National Journals (including IEEE, Springer, etc.) and Proceedings of the reputed International/ National Conferences (including Springer and IEEE). He has been nominated to the board of editors/reviewers of many peer-reviewed and refereed Journals (including IEEE, Springer).",institutionString:"Guru Ghasidas Vishwavidyalaya",institution:{name:"Guru Ghasidas Vishwavidyalaya",country:{name:"India"}}},{id:"246502",title:"Dr.",name:"Jaya T.",middleName:"T",surname:"Varkey",slug:"jaya-t.-varkey",fullName:"Jaya T. Varkey",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246502/images/11160_n.jpg",biography:"Jaya T. Varkey, PhD, graduated with a degree in Chemistry from Cochin University of Science and Technology, Kerala, India. She obtained a PhD in Chemistry from the School of Chemical Sciences, Mahatma Gandhi University, Kerala, India, and completed a post-doctoral fellowship at the University of Minnesota, USA. She is a research guide at Mahatma Gandhi University and Associate Professor in Chemistry, St. Teresa’s College, Kochi, Kerala, India.\nDr. Varkey received a National Young Scientist award from the Indian Science Congress (1995), a UGC Research award (2016–2018), an Indian National Science Academy (INSA) Visiting Scientist award (2018–2019), and a Best Innovative Faculty award from the All India Association for Christian Higher Education (AIACHE) (2019). She Hashas received the Sr. Mary Cecil prize for best research paper three times. She was also awarded a start-up to develop a tea bag water filter. \nDr. Varkey has published two international books and twenty-seven international journal publications. She is an editorial board member for five international journals.",institutionString:"St. Teresa’s College",institution:null},{id:"250668",title:"Dr.",name:"Ali",middleName:null,surname:"Nabipour Chakoli",slug:"ali-nabipour-chakoli",fullName:"Ali Nabipour Chakoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/250668/images/system/250668.jpg",biography:"Academic Qualification:\r\n•\tPhD in Materials Physics and Chemistry, From: Sep. 2006, to: Sep. 2010, School of Materials Science and Engineering, Harbin Institute of Technology, Thesis: Structure and Shape Memory Effect of Functionalized MWCNTs/poly (L-lactide-co-ε-caprolactone) Nanocomposites. Supervisor: Prof. Wei Cai,\r\n•\tM.Sc in Applied Physics, From: 1996, to: 1998, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Determination of Boron in Micro alloy Steels with solid state nuclear track detectors by neutron induced auto radiography, Supervisors: Dr. M. Hosseini Ashrafi and Dr. A. Hosseini.\r\n•\tB.Sc. in Applied Physics, From: 1991, to: 1996, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Design of shielding for Am-Be neutron sources for In Vivo neutron activation analysis, Supervisor: Dr. M. Hosseini Ashrafi.\r\n\r\nResearch Experiences:\r\n1.\tNanomaterials, Carbon Nanotubes, Graphene: Synthesis, Functionalization and Characterization,\r\n2.\tMWCNTs/Polymer Composites: Fabrication and Characterization, \r\n3.\tShape Memory Polymers, Biodegradable Polymers, ORC, Collagen,\r\n4.\tMaterials Analysis and Characterizations: TEM, SEM, XPS, FT-IR, Raman, DSC, DMA, TGA, XRD, GPC, Fluoroscopy, \r\n5.\tInteraction of Radiation with Mater, Nuclear Safety and Security, NDT(RT),\r\n6.\tRadiation Detectors, Calibration (SSDL),\r\n7.\tCompleted IAEA e-learning Courses:\r\nNuclear Security (15 Modules),\r\nNuclear Safety:\r\nTSA 2: Regulatory Protection in Occupational Exposure,\r\nTips & Tricks: Radiation Protection in Radiography,\r\nSafety and Quality in Radiotherapy,\r\nCourse on Sealed Radioactive Sources,\r\nCourse on Fundamentals of Environmental Remediation,\r\nCourse on Planning for Environmental Remediation,\r\nKnowledge Management Orientation Course,\r\nFood Irradiation - Technology, Applications and Good Practices,\r\nEmployment:\r\nFrom 2010 to now: Academic staff, Nuclear Science and Technology Research Institute, Kargar Shomali, Tehran, Iran, P.O. Box: 14395-836.\r\nFrom 1997 to 2006: Expert of Materials Analysis and Characterization. Research Center of Agriculture and Medicine. Rajaeeshahr, Karaj, Iran, P. O. Box: 31585-498.",institutionString:"Atomic Energy Organization of Iran",institution:{name:"Atomic Energy Organization of Iran",country:{name:"Iran"}}},{id:"248279",title:"Dr.",name:"Monika",middleName:"Elzbieta",surname:"Machoy",slug:"monika-machoy",fullName:"Monika Machoy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248279/images/system/248279.jpeg",biography:"Monika Elżbieta Machoy, MD, graduated with distinction from the Faculty of Medicine and Dentistry at the Pomeranian Medical University in 2009, defended her PhD thesis with summa cum laude in 2016 and is currently employed as a researcher at the Department of Orthodontics of the Pomeranian Medical University. She expanded her professional knowledge during a one-year scholarship program at the Ernst Moritz Arndt University in Greifswald, Germany and during a three-year internship at the Technical University in Dresden, Germany. She has been a speaker at numerous orthodontic conferences, among others, American Association of Orthodontics, European Orthodontic Symposium and numerous conferences of the Polish Orthodontic Society. She conducts research focusing on the effect of orthodontic treatment on dental and periodontal tissues and the causes of pain in orthodontic patients.",institutionString:"Pomeranian Medical University",institution:{name:"Pomeranian Medical University",country:{name:"Poland"}}},{id:"252743",title:"Prof.",name:"Aswini",middleName:"Kumar",surname:"Kar",slug:"aswini-kar",fullName:"Aswini Kar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252743/images/10381_n.jpg",biography:"uploaded in cv",institutionString:null,institution:{name:"KIIT University",country:{name:"India"}}},{id:"204256",title:"Dr.",name:"Anil",middleName:"Kumar",surname:"Kumar Sahu",slug:"anil-kumar-sahu",fullName:"Anil Kumar Sahu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204256/images/14201_n.jpg",biography:"I have nearly 11 years of research and teaching experience. I have done my master degree from University Institute of Pharmacy, Pt. Ravi Shankar Shukla University, Raipur, Chhattisgarh India. I have published 16 review and research articles in international and national journals and published 4 chapters in IntechOpen, the world’s leading publisher of Open access books. I have presented many papers at national and international conferences. I have received research award from Indian Drug Manufacturers Association in year 2015. My research interest extends from novel lymphatic drug delivery systems, oral delivery system for herbal bioactive to formulation optimization.",institutionString:null,institution:{name:"Chhattisgarh Swami Vivekanand Technical University",country:{name:"India"}}},{id:"253468",title:"Dr.",name:"Mariusz",middleName:null,surname:"Marzec",slug:"mariusz-marzec",fullName:"Mariusz Marzec",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/253468/images/system/253468.png",biography:"An assistant professor at Department of Biomedical Computer Systems, at Institute of Computer Science, Silesian University in Katowice. Scientific interests: computer analysis and processing of images, biomedical images, databases and programming languages. He is an author and co-author of scientific publications covering analysis and processing of biomedical images and development of database systems.",institutionString:"University of Silesia",institution:{name:"University of Silesia",country:{name:"Poland"}}},{id:"212432",title:"Prof.",name:"Hadi",middleName:null,surname:"Mohammadi",slug:"hadi-mohammadi",fullName:"Hadi Mohammadi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/212432/images/system/212432.jpeg",biography:"Dr. Hadi Mohammadi is a biomedical engineer with hands-on experience in the design and development of many engineering structures and medical devices through various projects that he has been involved in over the past twenty years. Dr. Mohammadi received his BSc. and MSc. degrees in Mechanical Engineering from Sharif University of Technology, Tehran, Iran, and his PhD. degree in Biomedical Engineering (biomaterials) from the University of Western Ontario. He was a postdoctoral trainee for almost four years at University of Calgary and Harvard Medical School. He is an industry innovator having created the technology to produce lifelike synthetic platforms that can be used for the simulation of almost all cardiovascular reconstructive surgeries. He’s been heavily involved in the design and development of cardiovascular devices and technology for the past 10 years. He is currently an Assistant Professor with the University of British Colombia, Canada.",institutionString:"University of British Columbia",institution:{name:"University of British Columbia",country:{name:"Canada"}}},{id:"254463",title:"Prof.",name:"Haisheng",middleName:null,surname:"Yang",slug:"haisheng-yang",fullName:"Haisheng Yang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/254463/images/system/254463.jpeg",biography:"Haisheng Yang, Ph.D., Professor and Director of the Department of Biomedical Engineering, College of Life Science and Bioengineering, Beijing University of Technology. He received his Ph.D. degree in Mechanics/Biomechanics from Harbin Institute of Technology (jointly with University of California, Berkeley). Afterwards, he worked as a Postdoctoral Research Associate in the Purdue Musculoskeletal Biology and Mechanics Lab at the Department of Basic Medical Sciences, Purdue University, USA. He also conducted research in the Research Centre of Shriners Hospitals for Children-Canada at McGill University, Canada. Dr. Yang has over 10 years research experience in orthopaedic biomechanics and mechanobiology of bone adaptation and regeneration. He earned an award from Beijing Overseas Talents Aggregation program in 2017 and serves as Beijing Distinguished Professor.",institutionString:null,institution:{name:"Beijing University of Technology",country:{name:"China"}}},{id:"89721",title:"Dr.",name:"Mehmet",middleName:"Cuneyt",surname:"Ozmen",slug:"mehmet-ozmen",fullName:"Mehmet Ozmen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/89721/images/7289_n.jpg",biography:null,institutionString:null,institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"265335",title:"Mr.",name:"Stefan",middleName:"Radnev",surname:"Stefanov",slug:"stefan-stefanov",fullName:"Stefan Stefanov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/265335/images/7562_n.jpg",biography:null,institutionString:null,institution:{name:"Medical University Plovdiv",country:{name:"Bulgaria"}}},{id:"242893",title:"Ph.D. Student",name:"Joaquim",middleName:null,surname:"De Moura",slug:"joaquim-de-moura",fullName:"Joaquim De Moura",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/242893/images/7133_n.jpg",biography:"Joaquim de Moura received his degree in Computer Engineering in 2014 from the University of A Coruña (Spain). In 2016, he received his M.Sc degree in Computer Engineering from the same university. He is currently pursuing his Ph.D degree in Computer Science in a collaborative project between ophthalmology centers in Galicia and the University of A Coruña. His research interests include computer vision, machine learning algorithms and analysis and medical imaging processing of various kinds.",institutionString:null,institution:{name:"University of A Coruña",country:{name:"Spain"}}},{id:"294334",title:"B.Sc.",name:"Marc",middleName:null,surname:"Bruggeman",slug:"marc-bruggeman",fullName:"Marc Bruggeman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/294334/images/8242_n.jpg",biography:"Chemical engineer graduate, with a passion for material science and specific interest in polymers - their near infinite applications intrigue me. \n\nI plan to continue my scientific career in the field of polymeric biomaterials as I am fascinated by intelligent, bioactive and biomimetic materials for use in both consumer and medical applications.",institutionString:null,institution:null},{id:"255757",title:"Dr.",name:"Igor",middleName:"Victorovich",surname:"Lakhno",slug:"igor-lakhno",fullName:"Igor Lakhno",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255757/images/system/255757.jpg",biography:"Igor Victorovich Lakhno was born in 1971 in Kharkiv (Ukraine). \nMD – 1994, Kharkiv National Medical Univesity.\nOb&Gyn; – 1997, master courses in Kharkiv Medical Academy of Postgraduate Education.\nPh.D. – 1999, Kharkiv National Medical Univesity.\nDSC – 2019, PL Shupik National Academy of Postgraduate Education \nProfessor – 2021, Department of Obstetrics and Gynecology of VN Karazin Kharkiv National University\nHead of Department – 2021, Department of Perinatology, Obstetrics and gynecology of Kharkiv Medical Academy of Postgraduate Education\nIgor Lakhno has been graduated from international training courses on reproductive medicine and family planning held at Debrecen University (Hungary) in 1997. Since 1998 Lakhno Igor has worked as an associate professor in the department of obstetrics and gynecology of VN Karazin National University and an associate professor of the perinatology, obstetrics, and gynecology department of Kharkiv Medical Academy of Postgraduate Education. Since June 2019 he’s been a professor in the department of obstetrics and gynecology of VN Karazin National University and a professor of the perinatology, obstetrics, and gynecology department. He’s affiliated with Kharkiv Medical Academy of Postgraduate Education as a Head of Department from November 2021. Igor Lakhno has participated in several international projects on fetal non-invasive electrocardiography (with Dr. J. A. Behar (Technion), Prof. D. Hoyer (Jena University), and José Alejandro Díaz Méndez (National Institute of Astrophysics, Optics, and Electronics, Mexico). He’s an author of about 200 printed works and there are 31 of them in Scopus or Web of Science databases. Igor Lakhno is a member of the Editorial Board of Reproductive Health of Woman, Emergency Medicine, and Technology Transfer Innovative Solutions in Medicine (Estonia). He is a medical Editor of “Z turbotoyu pro zhinku”. Igor Lakhno is a reviewer of the Journal of Obstetrics and Gynaecology (Taylor and Francis), British Journal of Obstetrics and Gynecology (Wiley), Informatics in Medicine Unlocked (Elsevier), The Journal of Obstetrics and Gynecology Research (Wiley), Endocrine, Metabolic & Immune Disorders-Drug Targets (Bentham Open), The Open Biomedical Engineering Journal (Bentham Open), etc. He’s defended a dissertation for a DSc degree “Pre-eclampsia: prediction, prevention, and treatment”. Three years ago Igor Lakhno has participated in a training course on innovative technologies in medical education at Lublin Medical University (Poland). Lakhno Igor has participated as a speaker in several international conferences and congresses (International Conference on Biological Oscillations April 10th-14th 2016, Lancaster, UK, The 9th conference of the European Study Group on Cardiovascular Oscillations). His main scientific interests: are obstetrics, women’s health, fetal medicine, and cardiovascular medicine. \nIgor Lakhno is a consultant at Kharkiv municipal perinatal center. He’s graduated from training courses on endoscopy in gynecology. He has 28 years of practical experience in the field.",institutionString:null,institution:null},{id:"244950",title:"Dr.",name:"Salvatore",middleName:null,surname:"Di Lauro",slug:"salvatore-di-lauro",fullName:"Salvatore Di Lauro",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0030O00002bSF1HQAW/ProfilePicture%202021-12-20%2014%3A54%3A14.482",biography:"Name:\n\tSALVATORE DI LAURO\nAddress:\n\tHospital Clínico Universitario Valladolid\nAvda Ramón y Cajal 3\n47005, Valladolid\nSpain\nPhone number: \nFax\nE-mail:\n\t+34 983420000 ext 292\n+34 983420084\nsadilauro@live.it\nDate and place of Birth:\nID Number\nMedical Licence \nLanguages\t09-05-1985. Villaricca (Italy)\n\nY1281863H\n474707061\nItalian (native language)\nSpanish (read, written, spoken)\nEnglish (read, written, spoken)\nPortuguese (read, spoken)\nFrench (read)\n\t\t\nCurrent position (title and company)\tDate (Year)\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. Private practise.\t2017-today\n\n2019-today\n\t\n\t\nEducation (High school, university and postgraduate training > 3 months)\tDate (Year)\nDegree in Medicine and Surgery. University of Neaples 'Federico II”\nResident in Opthalmology. Hospital Clinico Universitario Valladolid\nMaster in Vitreo-Retina. IOBA. University of Valladolid\nFellow of the European Board of Ophthalmology. Paris\nMaster in Research in Ophthalmology. University of Valladolid\t2003-2009\n2012-2016\n2016-2017\n2016\n2012-2013\n\t\nEmployments (company and positions)\tDate (Year)\nResident in Ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl.\nFellow in Vitreo-Retina. IOBA. University of Valladolid\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. \n\t2012-2016\n2016-2017\n2017-today\n\n2019-Today\n\n\n\t\nClinical Research Experience (tasks and role)\tDate (Year)\nAssociated investigator\n\n' FIS PI20/00740: DESARROLLO DE UNA CALCULADORA DE RIESGO DE\nAPARICION DE RETINOPATIA DIABETICA BASADA EN TECNICAS DE IMAGEN MULTIMODAL EN PACIENTES DIABETICOS TIPO 1. Grant by: Ministerio de Ciencia e Innovacion \n\n' (BIO/VA23/14) Estudio clínico multicéntrico y prospectivo para validar dos\nbiomarcadores ubicados en los genes p53 y MDM2 en la predicción de los resultados funcionales de la cirugía del desprendimiento de retina regmatógeno. Grant by: Gerencia Regional de Salud de la Junta de Castilla y León.\n' Estudio multicéntrico, aleatorizado, con enmascaramiento doble, en 2 grupos\nparalelos y de 52 semanas de duración para comparar la eficacia, seguridad e inmunogenicidad de SOK583A1 respecto a Eylea® en pacientes con degeneración macular neovascular asociada a la edad' (CSOK583A12301; N.EUDRA: 2019-004838-41; FASE III). Grant by Hexal AG\n\n' Estudio de fase III, aleatorizado, doble ciego, con grupos paralelos, multicéntrico para comparar la eficacia y la seguridad de QL1205 frente a Lucentis® en pacientes con degeneración macular neovascular asociada a la edad. (EUDRACT: 2018-004486-13). Grant by Qilu Pharmaceutical Co\n\n' Estudio NEUTON: Ensayo clinico en fase IV para evaluar la eficacia de aflibercept en pacientes Naive con Edema MacUlar secundario a Oclusion de Vena CenTral de la Retina (OVCR) en regimen de tratamientO iNdividualizado Treat and Extend (TAE)”, (2014-000975-21). Grant by Fundacion Retinaplus\n\n' Evaluación de la seguridad y bioactividad de anillos de tensión capsular en conejo. Proyecto Procusens. Grant by AJL, S.A.\n\n'Estudio epidemiológico, prospectivo, multicéntrico y abierto\\npara valorar la frecuencia de la conjuntivitis adenovírica diagnosticada mediante el test AdenoPlus®\\nTest en pacientes enfermos de conjuntivitis aguda”\\n. National, multicenter study. Grant by: NICOX.\n\nEuropean multicentric trial: 'Evaluation of clinical outcomes following the use of Systane Hydration in patients with dry eye”. Study Phase 4. Grant by: Alcon Labs'\n\nVLPs Injection and Activation in a Rabbit Model of Uveal Melanoma. Grant by Aura Bioscience\n\nUpdating and characterization of a rabbit model of uveal melanoma. Grant by Aura Bioscience\n\nEnsayo clínico en fase IV para evaluar las variantes genéticas de la vía del VEGF como biomarcadores de eficacia del tratamiento con aflibercept en pacientes con degeneración macular asociada a la edad (DMAE) neovascular. Estudio BIOIMAGE. IMO-AFLI-2013-01\n\nEstudio In-Eye:Ensayo clínico en fase IV, abierto, aleatorizado, de 2 brazos,\nmulticçentrico y de 12 meses de duración, para evaluar la eficacia y seguridad de un régimen de PRN flexible individualizado de 'esperar y extender' versus un régimen PRN según criterios de estabilización mediante evaluaciones mensuales de inyecciones intravítreas de ranibizumab 0,5 mg en pacientes naive con neovascularización coriodea secunaria a la degeneración macular relacionada con la edad. CP: CRFB002AES03T\n\nTREND: Estudio Fase IIIb multicéntrico, randomizado, de 12 meses de\nseguimiento con evaluador de la agudeza visual enmascarado, para evaluar la eficacia y la seguridad de ranibizumab 0.5mg en un régimen de tratar y extender comparado con un régimen mensual, en pacientes con degeneración macular neovascular asociada a la edad. CP: CRFB002A2411 Código Eudra CT:\n2013-002626-23\n\n\n\nPublications\t\n\n2021\n\n\n\n\n2015\n\n\n\n\n2021\n\n\n\n\n\n2021\n\n\n\n\n2015\n\n\n\n\n2015\n\n\n2014\n\n\n\n\n2015-16\n\n\n\n2015\n\n\n2014\n\n\n2014\n\n\n\n\n2014\n\n\n\n\n\n\n\n2014\n\nJose Carlos Pastor; Jimena Rojas; Salvador Pastor-Idoate; Salvatore Di Lauro; Lucia Gonzalez-Buendia; Santiago Delgado-Tirado. Proliferative vitreoretinopathy: A new concept of disease pathogenesis and practical\nconsequences. Progress in Retinal and Eye Research. 51, pp. 125 - 155. 03/2016. DOI: 10.1016/j.preteyeres.2015.07.005\n\n\nLabrador-Velandia S; Alonso-Alonso ML; Di Lauro S; García-Gutierrez MT; Srivastava GK; Pastor JC; Fernandez-Bueno I. Mesenchymal stem cells provide paracrine neuroprotective resources that delay degeneration of co-cultured organotypic neuroretinal cultures.Experimental Eye Research. 185, 17/05/2019. DOI: 10.1016/j.exer.2019.05.011\n\nSalvatore Di Lauro; Maria Teresa Garcia Gutierrez; Ivan Fernandez Bueno. Quantification of pigment epithelium-derived factor (PEDF) in an ex vivo coculture of retinal pigment epithelium cells and neuroretina.\nJournal of Allbiosolution. 2019. ISSN 2605-3535\n\nSonia Labrador Velandia; Salvatore Di Lauro; Alonso-Alonso ML; Tabera Bartolomé S; Srivastava GK; Pastor JC; Fernandez-Bueno I. Biocompatibility of intravitreal injection of human mesenchymal stem cells in immunocompetent rabbits. Graefe's archive for clinical and experimental ophthalmology. 256 - 1, pp. 125 - 134. 01/2018. DOI: 10.1007/s00417-017-3842-3\n\n\nSalvatore Di Lauro, David Rodriguez-Crespo, Manuel J Gayoso, Maria T Garcia-Gutierrez, J Carlos Pastor, Girish K Srivastava, Ivan Fernandez-Bueno. A novel coculture model of porcine central neuroretina explants and retinal pigment epithelium cells. Molecular Vision. 2016 - 22, pp. 243 - 253. 01/2016.\n\nSalvatore Di Lauro. Classifications for Proliferative Vitreoretinopathy ({PVR}): An Analysis of Their Use in Publications over the Last 15 Years. Journal of Ophthalmology. 2016, pp. 1 - 6. 01/2016. DOI: 10.1155/2016/7807596\n\nSalvatore Di Lauro; Rosa Maria Coco; Rosa Maria Sanabria; Enrique Rodriguez de la Rua; Jose Carlos Pastor. Loss of Visual Acuity after Successful Surgery for Macula-On Rhegmatogenous Retinal Detachment in a Prospective Multicentre Study. Journal of Ophthalmology. 2015:821864, 2015. DOI: 10.1155/2015/821864\n\nIvan Fernandez-Bueno; Salvatore Di Lauro; Ivan Alvarez; Jose Carlos Lopez; Maria Teresa Garcia-Gutierrez; Itziar Fernandez; Eva Larra; Jose Carlos Pastor. Safety and Biocompatibility of a New High-Density Polyethylene-Based\nSpherical Integrated Porous Orbital Implant: An Experimental Study in Rabbits. Journal of Ophthalmology. 2015:904096, 2015. DOI: 10.1155/2015/904096\n\nPastor JC; Pastor-Idoate S; Rodríguez-Hernandez I; Rojas J; Fernandez I; Gonzalez-Buendia L; Di Lauro S; Gonzalez-Sarmiento R. Genetics of PVR and RD. Ophthalmologica. 232 - Suppl 1, pp. 28 - 29. 2014\n\nRodriguez-Crespo D; Di Lauro S; Singh AK; Garcia-Gutierrez MT; Garrosa M; Pastor JC; Fernandez-Bueno I; Srivastava GK. Triple-layered mixed co-culture model of RPE cells with neuroretina for evaluating the neuroprotective effects of adipose-MSCs. Cell Tissue Res. 358 - 3, pp. 705 - 716. 2014.\nDOI: 10.1007/s00441-014-1987-5\n\nCarlo De Werra; Salvatore Condurro; Salvatore Tramontano; Mario Perone; Ivana Donzelli; Salvatore Di Lauro; Massimo Di Giuseppe; Rosa Di Micco; Annalisa Pascariello; Antonio Pastore; Giorgio Diamantis; Giuseppe Galloro. Hydatid disease of the liver: thirty years of surgical experience.Chirurgia italiana. 59 - 5, pp. 611 - 636.\n(Italia): 2007. ISSN 0009-4773\n\nChapters in books\n\t\n' Salvador Pastor Idoate; Salvatore Di Lauro; Jose Carlos Pastor Jimeno. PVR: Pathogenesis, Histopathology and Classification. Proliferative Vitreoretinopathy with Small Gauge Vitrectomy. Springer, 2018. ISBN 978-3-319-78445-8\nDOI: 10.1007/978-3-319-78446-5_2. \n\n' Salvatore Di Lauro; Maria Isabel Lopez Galvez. Quistes vítreos en una mujer joven. Problemas diagnósticos en patología retinocoroidea. Sociedad Española de Retina-Vitreo. 2018.\n\n' Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor Jimeno. iOCT in PVR management. OCT Applications in Opthalmology. pp. 1 - 8. INTECH, 2018. DOI: 10.5772/intechopen.78774.\n\n' Rosa Coco Martin; Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor. amponadores, manipuladores y tinciones en la cirugía del traumatismo ocular.Trauma Ocular. Ponencia de la SEO 2018..\n\n' LOPEZ GALVEZ; DI LAURO; CRESPO. OCT angiografia y complicaciones retinianas de la diabetes. PONENCIA SEO 2021, CAPITULO 20. (España): 2021.\n\n' Múltiples desprendimientos neurosensoriales bilaterales en paciente joven. Enfermedades Degenerativas De Retina Y Coroides. SERV 04/2016. \n' González-Buendía L; Di Lauro S; Pastor-Idoate S; Pastor Jimeno JC. Vitreorretinopatía proliferante (VRP) e inflamación: LA INFLAMACIÓN in «INMUNOMODULADORES Y ANTIINFLAMATORIOS: MÁS ALLÁ DE LOS CORTICOIDES. 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