Modified GOSLON yardstick (GOSLON+) for patients with UCLP. A similar table apply to patients with BCLP.
\\n\\n
These books synthesize perspectives of renowned scientists from the world’s most prestigious institutions - from Fukushima Renewable Energy Institute in Japan to Stanford University in the United States, including Columbia University (US), University of Sidney (AU), University of Miami (USA), Cardiff University (UK), and many others.
\\n\\nThis collaboration embodied the true essence of Open Access by simplifying the approach to OA publishing for Academic editors and authors who contributed their research and allowed the new research to be made available free and open to anyone anywhere in the world.
\\n\\nTo celebrate the 50 books published, we have gathered them at one location - just one click away, so that you can easily browse the subjects of your interest, download the content directly, share it or read online.
\\n\\n\\n\\n\\n"}]',published:!0,mainMedia:null},components:[{type:"htmlEditorComponent",content:'
IntechOpen and Knowledge Unlatched formed a partnership to support researchers working in engineering sciences by enabling an easier approach to publishing Open Access content. Using the Knowledge Unlatched crowdfunding model to raise the publishing costs through libraries around the world, Open Access Publishing Fee (OAPF) was not required from the authors.
\n\nInitially, the partnership supported engineering research, but it soon grew to include physical and life sciences, attracting more researchers to the advantages of Open Access publishing.
\n\n\n\nThese books synthesize perspectives of renowned scientists from the world’s most prestigious institutions - from Fukushima Renewable Energy Institute in Japan to Stanford University in the United States, including Columbia University (US), University of Sidney (AU), University of Miami (USA), Cardiff University (UK), and many others.
\n\nThis collaboration embodied the true essence of Open Access by simplifying the approach to OA publishing for Academic editors and authors who contributed their research and allowed the new research to be made available free and open to anyone anywhere in the world.
\n\nTo celebrate the 50 books published, we have gathered them at one location - just one click away, so that you can easily browse the subjects of your interest, download the content directly, share it or read online.
\n\n\n\n\n'}],latestNews:[{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"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"6578",leadTitle:null,fullTitle:"Data Mining",title:"Data Mining",subtitle:null,reviewType:"peer-reviewed",abstract:"This book on data mining explores a broad set of ideas and presents some of the state-of-the-art research in this field. The book is triggered by pervasive applications that retrieve knowledge from real-world big data. Data mining finds applications in the entire spectrum of science and technology including basic sciences to life sciences and medicine, to social, economic, and cognitive sciences, to engineering and computers. The chapters discuss various applications and research frontiers in data mining with algorithms and implementation details for use in real-world. This can be through characterization, classification, discrimination, anomaly detection, association, clustering, trend or evolution prediction, etc. The intended audience of this book will mainly consist of researchers, research students, practitioners, data analysts, and business professionals who seek information on the various data mining techniques and their applications.",isbn:"978-1-78923-597-5",printIsbn:"978-1-78923-596-8",pdfIsbn:"978-1-83881-567-7",doi:"10.5772/intechopen.71371",price:119,priceEur:129,priceUsd:155,slug:"data-mining",numberOfPages:190,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"4f09e58a93ed74f9d1d5600f6d6e518c",bookSignature:"Ciza Thomas",publishedDate:"August 22nd 2018",coverURL:"https://cdn.intechopen.com/books/images_new/6578.jpg",numberOfDownloads:12119,numberOfWosCitations:4,numberOfCrossrefCitations:11,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:14,numberOfDimensionsCitationsByBook:0,hasAltmetrics:1,numberOfTotalCitations:29,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"October 10th 2017",dateEndSecondStepPublish:"October 31st 2017",dateEndThirdStepPublish:"January 5th 2018",dateEndFourthStepPublish:"March 20th 2018",dateEndFifthStepPublish:"May 19th 2018",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"43680",title:"Prof.",name:"Ciza",middleName:null,surname:"Thomas",slug:"ciza-thomas",fullName:"Ciza Thomas",profilePictureURL:"https://mts.intechopen.com/storage/users/43680/images/system/43680.jpeg",biography:"Dr. Ciza Thomas is currently Senior Joint Director at the Directorate of Technical Education, Government of Kerala, India. Her area of expertise is network security with research interest in the fields of information security, data mining, sensor fusion, pattern recognition, information retrieval, digital signal processing, and image processing. She has more than eighty journal papers and fifty conference publications to her credit. She has edited nine books and published sixteen book chapters. She is a reviewer of more than ten international journals including IEEE Transactions on Signal Processing, IEEE Transactions on Neural Networks, International Journal of Network Security, International Journal of Network Management, and Security and Communications Network. Dr. Thomas received an achievement award in 2010 and an e-learning IT award in 2014 from the Government of Kerala.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"6",institution:{name:"Government of Kerala",institutionURL:null,country:{name:"India"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"606",title:"Machine Learning and Data Mining",slug:"numerical-analysis-and-scientific-computing-machine-learning-and-data-mining"}],chapters:[{id:"59416",title:"Ensemble Methods in Environmental Data Mining",doi:"10.5772/intechopen.74393",slug:"ensemble-methods-in-environmental-data-mining",totalDownloads:1366,totalCrossrefCites:3,totalDimensionsCites:4,hasAltmetrics:0,abstract:"Environmental data mining is the nontrivial process of identifying valid, novel, and potentially useful patterns in data from environmental sciences. This chapter proposes ensemble methods in environmental data mining that combines the outputs from multiple classification models to obtain better results than the outputs that could be obtained by an individual model. The study presented in this chapter focuses on several ensemble strategies in addition to the standard single classifiers such as decision tree, naive Bayes, support vector machine, and k-nearest neighbor (KNN), popularly used in literature. This is the first study that compares four ensemble strategies for environmental data mining: (i) bagging, (ii) bagging combined with random feature subset selection (the random forest algorithm), (iii) boosting (the AdaBoost algorithm), and (iv) voting of different algorithms. In the experimental studies, ensemble methods are tested on different real-world environmental datasets in various subjects such as air, ecology, rainfall, and soil.",signatures:"Goksu Tuysuzoglu, Derya Birant and Aysegul Pala",downloadPdfUrl:"/chapter/pdf-download/59416",previewPdfUrl:"/chapter/pdf-preview/59416",authors:[{id:"15609",title:"Dr.",name:"Derya",surname:"Birant",slug:"derya-birant",fullName:"Derya Birant"},{id:"231573",title:"Ms.",name:"Goksu",surname:"Tuysuzoglu",slug:"goksu-tuysuzoglu",fullName:"Goksu Tuysuzoglu"},{id:"231574",title:"Prof.",name:"Aysegul",surname:"Pala",slug:"aysegul-pala",fullName:"Aysegul Pala"}],corrections:null},{id:"61571",title:"Estimating Customer Lifetime Value Using Machine Learning Techniques",doi:"10.5772/intechopen.76990",slug:"estimating-customer-lifetime-value-using-machine-learning-techniques",totalDownloads:2264,totalCrossrefCites:2,totalDimensionsCites:2,hasAltmetrics:0,abstract:"With the rapid development of civil aviation industry, high-quality customer resources have become a significant way to measure the competitiveness of the civil aviation industry. It is well known that the competition for high-value customers has become the core of airline profits. The research of airline customer lifetime value can help airlines identify high-value, medium-value and low-value travellers. What is more, the airline company can make resource allocation more rational, with the least resource investment for maximum profit return. However, the models that are used to calculate the value of customer life value remain controversial, and how to design a model that applies to airline company still needs to be explored. In the paper, the author proposed the optimised China Eastern Airlines passenger network value assessment model and examined its fitting degree with the TravelSky value score. Besides, the author combines China Eastern Airlines passenger network value assessment model score with loss model score to help airlines find their significant customers.",signatures:"Sien Chen",downloadPdfUrl:"/chapter/pdf-download/61571",previewPdfUrl:"/chapter/pdf-preview/61571",authors:[{id:"203722",title:"Dr.",name:"Sien",surname:"Chen",slug:"sien-chen",fullName:"Sien Chen"}],corrections:null},{id:"60203",title:"Determination and Classification of Crew Productivity with Data Mining Methods",doi:"10.5772/intechopen.75504",slug:"determination-and-classification-of-crew-productivity-with-data-mining-methods",totalDownloads:1001,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Turkey is a developing country and the main axis of development is “construction.” The construction sector is in a position to create demand for goods and services produced by more than 200 subsectors, and this widespread impact is the most basic indicator of the sector’s “locomotive of the economy.” In the development of the construction industry, crew productivity plays a very important role. While businesses that do not measure their employees’ needs, their locations, and so on are suffering from various losses, rare businesses that take these parameters into account can profit. The identification of leadership types that will motivate employees has great importance in terms of construction businesses where the human element is the foreground. For this purpose, in the province of Adana, the relationship of productivity between the engineers working in construction companies and workers who work at lower departments of these engineers was examined. In this study, bidirectional multiple leadership questionnaire (MLQ) was applied to construction site managers and employees, and according to this survey data, leadership and motivations/productivities were classified using data mining methods. According to the classification analysis results, the most successful data mining algorithm was random forest algorithm with a rate of 81.3725%.",signatures:"Abdullah Emre Keleş and Mümine Kaya Keleş",downloadPdfUrl:"/chapter/pdf-download/60203",previewPdfUrl:"/chapter/pdf-preview/60203",authors:[{id:"190444",title:"Dr.",name:"Mümine",surname:"Kaya Keleş",slug:"mumine-kaya-keles",fullName:"Mümine Kaya Keleş"},{id:"233416",title:"Dr.",name:"Abdullah Emre",surname:"Keleş",slug:"abdullah-emre-keles",fullName:"Abdullah Emre Keleş"}],corrections:null},{id:"60392",title:"Mining HCI Data for Theory of Mind Induction",doi:"10.5772/intechopen.74400",slug:"mining-hci-data-for-theory-of-mind-induction",totalDownloads:1179,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Human-computer interaction (HCI) results in enormous amounts of data-bearing potentials for understanding a human user’s intentions, goals, and desires. Knowing what users want and need is a key to intelligent system assistance. The theory of mind concept known from studies in animal behavior is adopted and adapted for expressive user modeling. Theories of mind are hypothetical user models representing, to some extent, a human user’s thoughts. A theory of mind may even reveal tacit knowledge. In this way, user modeling becomes knowledge discovery going beyond the human’s knowledge and covering domain-specific insights. Theories of mind are induced by mining HCI data. Data mining turns out to be inductive modeling. Intelligent assistant systems inductively modeling a human user’s intentions, goals, and the like, as well as domain knowledge are, by nature, learning systems. To cope with the risk of getting it wrong, learning systems are equipped with the skill of reflection.",signatures:"Oksana Arnold and Klaus P. Jantke",downloadPdfUrl:"/chapter/pdf-download/60392",previewPdfUrl:"/chapter/pdf-preview/60392",authors:[{id:"226993",title:"Dr.",name:"Klaus",surname:"Jantke",slug:"klaus-jantke",fullName:"Klaus Jantke"},{id:"233087",title:"Prof.",name:"Oksana",surname:"Arnold",slug:"oksana-arnold",fullName:"Oksana Arnold"}],corrections:null},{id:"60500",title:"Performance-Aware High-Performance Computing for Remote Sensing Big Data Analytics",doi:"10.5772/intechopen.75934",slug:"performance-aware-high-performance-computing-for-remote-sensing-big-data-analytics",totalDownloads:1023,totalCrossrefCites:2,totalDimensionsCites:3,hasAltmetrics:0,abstract:"The incredible increase in the volume of data emerging along with recent technological developments has made the analysis processes which use traditional approaches more difficult for many organizations. Especially applications involving subjects that require timely processing and big data such as satellite imagery, sensor data, bank operations, web servers, and social networks require efficient mechanisms for collecting, storing, processing, and analyzing these data. At this point, big data analytics, which contains data mining, machine learning, statistics, and similar techniques, comes to the help of organizations for end-to-end managing of the data. In this chapter, we introduce a novel high-performance computing system on the geo-distributed private cloud for remote sensing applications, which takes advantages of network topology, exploits utilization and workloads of CPU, storage, and memory resources in a distributed fashion, and optimizes resource allocation for realizing big data analytics efficiently.",signatures:"Mustafa Kemal Pektürk and Muhammet Ünal",downloadPdfUrl:"/chapter/pdf-download/60500",previewPdfUrl:"/chapter/pdf-preview/60500",authors:[{id:"229796",title:"Ph.D. Student",name:"Mustafa Kemal",surname:"Pektürk",slug:"mustafa-kemal-pekturk",fullName:"Mustafa Kemal Pektürk"},{id:"243763",title:"Dr.",name:"Muhammet",surname:"Ünal",slug:"muhammet-unal",fullName:"Muhammet Ünal"}],corrections:null},{id:"61379",title:"Early Prediction of Patient Mortality Based on Routine Laboratory Tests and Predictive Models in Critically Ill Patients",doi:"10.5772/intechopen.76988",slug:"early-prediction-of-patient-mortality-based-on-routine-laboratory-tests-and-predictive-models-in-cri",totalDownloads:991,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"We propose a method for quantitative analysis of predictive power of laboratory tests and early detection of mortality risk by usage of predictive models and feature selection techniques. Our method allows automatic feature selection, model selection, and evaluation of predictive models. Experimental evaluation was conducted on patients with renal failure admitted to ICUs (medical intensive care, surgical intensive care, cardiac, and cardiac surgery recovery units) at Boston’s Beth Israel Deaconess Medical Center. Data are extracted from Multi parameter Intelligent Monitoring in Intensive Care III (MIMIC-III) database. We built and evaluated different single (e.g. Logistic regression) and ensemble (e.g. Random Forest) learning methods. Results revealed high predictive accuracy (area under the precision-recall curve (AUPRC) values >86%) from day four, with acceptable results on the second (>81%) and third day (>85%). Random forests seem to provide the best predictive accuracy. Feature selection techniques Gini and ReliefF scored best in most cases. Lactate, white blood cells, sodium, anion gap, chloride, bicarbonate, creatinine, urea nitrogen, potassium, glucose, INR, hemoglobin, phosphate, total bilirubin, and base excess were most predictive for hospital mortality. Ensemble learning methods are able to predict hospital mortality with high accuracy, based on laboratory tests and provide ranking in predictive priority.",signatures:"Sven Van Poucke, Ana Kovacevic and Milan Vukicevic",downloadPdfUrl:"/chapter/pdf-download/61379",previewPdfUrl:"/chapter/pdf-preview/61379",authors:[{id:"229238",title:"Ph.D.",name:"Milan",surname:"Vukicevic",slug:"milan-vukicevic",fullName:"Milan Vukicevic"},{id:"232036",title:"Dr.",name:"Sven",surname:"Van Poucke",slug:"sven-van-poucke",fullName:"Sven Van Poucke"},{id:"240289",title:"MSc.",name:"Ana",surname:"Kovacevic",slug:"ana-kovacevic",fullName:"Ana Kovacevic"}],corrections:null},{id:"61764",title:"Semantic Infrastructure for Service Environment Supporting Successful Aging",doi:"10.5772/intechopen.76945",slug:"semantic-infrastructure-for-service-environment-supporting-successful-aging",totalDownloads:1112,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Demographic changes and the rapid increase of aging people are occurring throughout the world. There is a need for step-by-step developing service environment to support elderly living as old as possible at home. Digital equipment and technology solutions installed at home produce real-time data which can be used for predictive and optimized service creation. New technology solutions have to be tested at home environments to get certainty of usability, flexibility, and accessibility. The implementation of new digitalization has to happen according to ethical rules taking into account the values of elderly people. The data gathered through digital equipment is used in optimizing service processes. However, service process misses common ontology and semantic infrastructure to use the gathered data for service optimization. The service environment and semantic infrastructure, which could be used in social and health care, are introduced in this article.",signatures:"Vesa Salminen, Päivi Sanerma, Seppo Niittymäki and Patrick Eklund",downloadPdfUrl:"/chapter/pdf-download/61764",previewPdfUrl:"/chapter/pdf-preview/61764",authors:[{id:"150157",title:"Prof.",name:"Patrik",surname:"Eklund",slug:"patrik-eklund",fullName:"Patrik Eklund"},{id:"214042",title:"Dr.",name:"Vesa",surname:"Salminen",slug:"vesa-salminen",fullName:"Vesa Salminen"},{id:"229313",title:"Dr.",name:"Päivi",surname:"Sanerma",slug:"paivi-sanerma",fullName:"Päivi Sanerma"},{id:"229315",title:"Dr.",name:"Seppo",surname:"Niittymaki",slug:"seppo-niittymaki",fullName:"Seppo Niittymaki"}],corrections:null},{id:"62381",title:"Adaptive Neural Network Classifier-Based Analysis of Big Data in Health Care",doi:"10.5772/intechopen.77225",slug:"adaptive-neural-network-classifier-based-analysis-of-big-data-in-health-care",totalDownloads:1008,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Because of the massive volume, variety, and continuous updating of medical data, the efficient processing of medical data and the real-time response of the treatment recommendation has become an important issue. Fortunately, parallel computing and cloud computing provide powerful capabilities to cope with large-scale data. Therefore, in this paper, a FCM based Map-Reduce programming model is proposed for the parallel computing using AANN approach. The FCM based Map-Reduce, clusters the large medical datasets into smaller groups of certain similarity and assigns each data cluster to one Mapper, where the training of neural networks are done by the optimal selection of the interconnection weights by Whale Optimization Algorithm (WOA). Finally, the Reducer reduces all the AANN classifiers obtained from the Mappers for identifying the normal and abnormal classes of the newer medical records promptly and accurately. The proposed methodology is implemented in the working platform of JAVA using CloudSim simulator.",signatures:"Manaswini Pradhan",downloadPdfUrl:"/chapter/pdf-download/62381",previewPdfUrl:"/chapter/pdf-preview/62381",authors:[{id:"228706",title:"Dr.",name:"Manaswini",surname:"Pradhan",slug:"manaswini-pradhan",fullName:"Manaswini Pradhan"}],corrections:null},{id:"61956",title:"Identification of Research Thematic Approaches Based on Keywords Network Analysis in Colombian Social Sciences",doi:"10.5772/intechopen.76834",slug:"identification-of-research-thematic-approaches-based-on-keywords-network-analysis-in-colombian-socia",totalDownloads:1086,totalCrossrefCites:2,totalDimensionsCites:2,hasAltmetrics:0,abstract:"The purpose of this research was to unveil the structure of knowledge of Social Sciences in Colombia through the analysis of thematic networks and its association with different disciplines’ new knowledge production to define scenarios and trends in each. 2992 published articles in the period 2006–2015 were revised in this research, all indexed in Web of Science, Scopus and other bibliographic databases, applying the social networks analysis technique to the keywords of all. The analysis included each discipline’s clustering coefficient and group metrics. The results described in this chapter identify how social disciplines in Colombia have mainly focused its research production in topics such as armed conflict, poverty and human development.",signatures:"José Hernando Ávila-Toscano, Ivón Catherine Romero-Pérez, Ailed\nMarenco-Escuderos and Eugenio Saavedra Guajardo",downloadPdfUrl:"/chapter/pdf-download/61956",previewPdfUrl:"/chapter/pdf-preview/61956",authors:[{id:"239597",title:"Ph.D.",name:"Jose",surname:"Ávila",slug:"jose-avila",fullName:"Jose Ávila"},{id:"239600",title:"Dr.",name:"Eugenio",surname:"Saavedra",slug:"eugenio-saavedra",fullName:"Eugenio Saavedra"},{id:"239601",title:"MSc.",name:"Ailed",surname:"Marenco",slug:"ailed-marenco",fullName:"Ailed Marenco"},{id:"239602",title:"MSc.",name:"Ivon",surname:"Romero",slug:"ivon-romero",fullName:"Ivon Romero"}],corrections:null},{id:"61359",title:"Data Privacy for Big Data Publishing Using Newly Enhanced PASS Data Mining Mechanism",doi:"10.5772/intechopen.77033",slug:"data-privacy-for-big-data-publishing-using-newly-enhanced-pass-data-mining-mechanism",totalDownloads:1089,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Anonymization is one of the main techniques that is being used in recent times to prevent privacy breaches on the published data; one such anonymization technique is k-anonymization technique. The anonymization is a parametric anonymization technique used for data anonymization. The aim of the k-anonymization is to generalize the tuples in a way that it cannot be identified using quasi-identifiers. In the past few years, we saw a tremendous growth in data that ultimately led to the concept of the big data. The growth in data made anonymization using conventional processing methods inefficient. To make the anonymization more efficient, we used the proposed PASS mechanism in Hadoop framework to reduce the processing time of anonymization. In this work, we have divided the whole program into the map and reduce part. Moreover, the data types used in Hadoop provide better serialization and transport of data. We performed our experiments on the large dataset. The results proved the best efficiency of our implementation.",signatures:"Priyank Jain, Manasi Gyanchandani and Nilay Khare",downloadPdfUrl:"/chapter/pdf-download/61359",previewPdfUrl:"/chapter/pdf-preview/61359",authors:[{id:"229813",title:"Mr.",name:"Priyank",surname:"Jain",slug:"priyank-jain",fullName:"Priyank Jain"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"155",title:"Sensor Fusion",subtitle:"Foundation and Applications",isOpenForSubmission:!1,hash:"4e394b8458dc49549ccf603ef6e376b8",slug:"sensor-fusion-foundation-and-applications",bookSignature:"Ciza Thomas",coverURL:"https://cdn.intechopen.com/books/images_new/155.jpg",editedByType:"Edited by",editors:[{id:"43680",title:"Prof.",name:"Ciza",surname:"Thomas",slug:"ciza-thomas",fullName:"Ciza Thomas"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5844",title:"Ontology in Information Science",subtitle:null,isOpenForSubmission:!1,hash:"922bcfea0d27e7e004542ce3adca6d20",slug:"ontology-in-information-science",bookSignature:"Ciza Thomas",coverURL:"https://cdn.intechopen.com/books/images_new/5844.jpg",editedByType:"Edited by",editors:[{id:"43680",title:"Prof.",name:"Ciza",surname:"Thomas",slug:"ciza-thomas",fullName:"Ciza Thomas"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5386",title:"Complex Systems, Sustainability and Innovation",subtitle:null,isOpenForSubmission:!1,hash:"38584277d8d21713ab23b920761f35e4",slug:"complex-systems-sustainability-and-innovation",bookSignature:"Ciza Thomas",coverURL:"https://cdn.intechopen.com/books/images_new/5386.jpg",editedByType:"Edited by",editors:[{id:"43680",title:"Prof.",name:"Ciza",surname:"Thomas",slug:"ciza-thomas",fullName:"Ciza Thomas"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9234",title:"Computer Security Threats",subtitle:null,isOpenForSubmission:!1,hash:"23d6de178880e547c39ec4e503777dcd",slug:"computer-security-threats",bookSignature:"Ciza Thomas, Paula Fraga-Lamas and Tiago M. 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Signal processing refers to the science of analyzing time‐varying physical processes [1]. Signal processing is divided into two categories: analog signal processing and digital signal processing. An analog signal is continuous in time and can take on a continuous range of amplitude values. A discrete‐time signal is an independent time variable that is quantized so that only the value of the signal at the discrete instant in time is known. This can be illustrated in the following example: a continuous sinewave with peak amplitude of 1 and frequency of
where the frequency
By plotting Eq. (1) a continuous curve is obtained (Figure 1a). If the continuous waveform represents a continuous physical voltage sampling every
A time‐domain sinewave: (a) continuous waveform representation and (b) discrete sample representation.
Filters are used for two general purposes: (1) separation of signals that have been combined and (2) restoration of signals that have been distorted in some form. Signal separation is needed when if the signal is contaminated by interference, noise or other signals. As an example, filtering is used to separate nonphysiologic high‐frequency pulmonary vein potentials recorded during catheter ablation of atrial fibrillation (AF) from physiologic signals. Signal restoration is used when a signal has been distorted in some form. For example, an audio recording obtained with poor equipment may be filtered to improve fidelity so the actual sound is better reproduced.
For raw signal data to be analyzed, information must be represented in either the time or frequency domain. The most commonly used filters applied in intracardiac devices are in the frequency domain. Figure 2 summarizes the four most common basic frequency responses. These filters allow unaltered passing of some frequencies, while other frequencies are completely blocked. Those frequencies that pass through are called “passband,” while frequencies that are blocked are referred to as “stopband.” The band in‐between is called the “transition band.” A very narrow transition band is called “fast roll‐off,” “The cut‐off frequency” is the frequency that separates the “passband” from the “transition band,” Analog filters use a cut‐off frequency that is decreased to 0.707 from the original amplitude. Digital filters are less strict, and usually the cut‐offs used are 99, 90, 70.7, and 50% of the original amplitude levels.
The four common frequency responses.
The example shown in Figure 3 highlights the three parameters described above. An example of a “fast roll‐off,” is shown in (a) and (b). A “passband ripple” example is shown in (c) and (d), and finally, “stopband attenuation” is shown in (e) and (f).
The three parameters important for evaluating frequency domain performance: (1) roll‐off sharpness, (a) and (b); (2) passband ripple, (c) and (d); and (3) stopband attenuation, (e) and (f).
Chebyshev filters are used to separate one band of frequencies from another. They are the most commonly used in cardiac electrophysiology applications. The primary attribute of Chebyshev filters is their speed. The Chebyshev response is a mathematical strategy for achieving a faster “roll‐off” by allowing “ripple” in the frequency response.
Figure 4 shows three ripple values, 0, 0.5, and 20%, for a low‐pass Chebyshev filter. If the ripple decreases (good) the roll‐off becomes less sharp (bad). The Chebyshev filter design is an optimal balance between these two parameters. If the ripple is 0%, the filter is called “Butterworth filter.” A ripple of 0.5% is often a good choice for digital filters. This matches the typical precision and accuracy of the analog electronics that the signal has passed through.
The Chebyshev response: Chebyshev filters achieve a faster roll‐off by allowing ripple in the passband. When the ripple is set to 0%, it is called a maximally flat or Butterworth filter.
All electrical circuits must have a cathode (negative pole) and an anode (positive pole) [2]. In general, there are two types of electrical circuits used in pacing systems depending on the location of the anode. In a unipolar system, as shown in Figure 5(a), the metal can of the pacemaker is used as the anode (+), and the distal electrode of pacemaker lead as the cathode (−). In a unipolar system, the pacing lead has only one electrical pole. Figure 5(b) shows the other type, a BIPOLAR system where both the anode (+) and cathode (−) are located on the same pacing lead. In all pacing systems, the distal pole that is in direct contact with cardiac tissue is negative. All currently available ICDs are bipolar, however, based on the lead utilized, the system may be dedicated bipolar or integrated bipolar. In a dedicated bipolar design, the anode is separate from the shock coil. In an integrated design, the distal shock coil also serves as the anode for pacing and sensing. An integrated design allows for more simple lead construction, as the distal shock coil serves two purposes. A dedicated bipolar system may provide more reliable sensing than an integrated design with a shared coil, as the anode is not affected by the high‐voltage shock. Unipolar pacing systems have the advantage of a simpler and more reliable single‐coil lead construction. It is also much easier to appreciate the pacing artifact of a unipolar system due to the anatomic distance between lead and pulse generator with parts of the electrical circuit closer to the skin surface. In some instances, sensing and capture thresholds are better than those obtained from a bipolar system, although lower lead impedance may result in higher current drain from the battery. In order to reduce the risk of pacemaker stimulation of the pectoralis muscle and/or device oversensing of electrical signals generated by the pectoralis muscle, many of the older pacemaker models incorporated a layer of protective coating on the device side facing the muscular tissue.
(a) Unipolar pacing system: the lead tip is the cathode and the pacemaker is the anode. (b) Bipolar pacing system: the lead tip is the cathode and the proximal ring is the anode. The pacemaker is not part of the circuit.
Bipolar pacing systems offer several advantages that have made this polarity choice increasingly popular, especially as dual‐chamber pacing has become more prevalent in clinical practice. Because the distance between the individual electrodes is small (short antenna) and since both are located deep within the body, bipolar devices are less susceptible than unipolar systems to electrical interference caused by skeletal muscle activity or electromagnetic interference (EMI). Also, higher output settings required for unipolar pacing may result in stimulation of the pocket around the pacemaker. This problem is virtually unknown in normally functioning bipolar systems. One downside to using bipolar pacing is that the pacing artifact is very small and often difficult to discern on the surface electrocardiogram. This makes determination of proper function and malfunction more difficult. For this reason, it is not uncommon to see a pacemaker programmed to unipolar pacing but bipolar sensing.
Sensing is the ability of the device to detect the intrinsic cardiac activity [3]. This is measured in millivolts (mV). The larger the signal in mV, the easier it is for the device to sense the event as well as to discriminate normal intrinsic from spurious electrical signals. Setting the sensitivity of a pacemaker is often confusing. When programming this value, it must be understood that the value programmed is the smallest amplitude signal that will be sensed (Figure 6). There is an inverse relation between sensing and sensitivity. The higher the sensing value, the lower the sensitivity to detect the intrinsic electrical signal. Thus, a setting of 8 mV requires at least an 8 mV electrical signal for the pacemaker to detect. A 2 mV setting will allow any signal above 2 mV to be sensed by the pacemaker.
Concept of sensitivity. Electrogram A is 3 mV in size and electrogram B is 10 mV in size. At sensitivity of 2 mV, both electrical signals have sufficient amplitude to be sensed. At setting of 8 mV, only the larger signal will be sensed.
Measurement of the intrinsic electrical signal for sensing is not simple, as the pacemaker does not use the entire electrical signal that is present. This “raw” electrical signal is filtered to eliminate a majority of noncardiac signals as well as portions of the cardiac signals that are not needed. Because filtering allows only certain frequencies to pass through to the sensing circuit, the final “filtered” signal may be substantially different from the original signal (Figure 7). One way of measuring the quality of a sensed signal is to look at the slew rate. The slew rate refers to the slope of the intrinsic signal (Figure 8) and is measured in volts/second. High slew rates (>1.0 V/s in the ventricle and >0.5 V/s in the atrium) are desirable for consistent sensing.
Raw and filtered electrograms sensed by a pacemaker. The top tracing is the filtered signal used by the pacemaker for sensing. Filtering of the raw signal is necessary to prevent (over)sensing of the T‐wave, far‐field signals, and myopotentials.
Slew rate measured in volt/second. The more rapid the voltage increase, the sharper the electrogram, the higher the slew rate.
As pacing systems become increasingly sophisticated, programming optimal pacing and sensing parameters for individual patients also becomes more difficult [4]. In addition, biological systems by nature are constantly changing, making settings that are appropriate at one point in time inappropriate at other times. Some pacemakers now have algorithms to automatically adjust one or more parameters. Automaticity is commonly applied to the rate response sensor function and sensitivity. There are different sensitivity adjusting algorithms for pacemakers and ICDs. For pacemakers, these algorithms assess the size of the sensed signal, and then attempt to provide a safety margin by adjusting the sensitivity. This tends to result in a less sensitive setting for the ventricle, as much of the time ventricular signals are very large. Lowering the susceptibility to EMI, it may in turn cause occasional undersensing of ectopic intrinsic beats. For a bipolar pacing system, the nominal (“out of the box”) sensitivity settings are usually acceptable and rarely result in under‐ or oversensing. Some pacemakers utilize an automatic gain feature similar to that of ICDs, which differs from the automatic adjustment feature currently in use in that the programmed sensing values remain unaffected (Figure 9).
(a) Auto gain is a method to automate the sensing function. Sensitivity increases with the length of the sensing interval. Once a signal is sensed, the sensitivity abruptly decreases to avoid oversensing of the evoked response and the T‐wave. (b) Autosensing adjustment is a method to automatically set the sensitivity. An inner and upper target is set for sensing. When a beat is sensed on both the inner and upper targets, the upper target is moved further out (made less sensitive) until sensing no longer occurs. The upper target is then moved back. In this way, the device can determine the signal amplitude and set the overall sensitivity of the device appropriately.
Sensing the intrinsic heart rate is very important as this is the primary method for the ICD to detect the presence of a tachycardia. Typically, true bipolar and integrated bipolar configurations are used, while unipolar pacing and sensing have no role in ICD programming. True bipolar sensing in ICDs uses the same methodology as for conventional pacing leads. The dedicated pacing and sensing cathode and anode are located toward the distal tip of the lead within the ventricle (Figure 10a) and kept separate from the high‐voltage shocking circuit. In an integrated bipolar configuration, the lead tip serves as the cathode and the distal shocking coil as the anode (Figure 10b) allowing for simpler lead design. However, since the shock coil doubles as the sensing coil, suboptimal sensing may result immediately after a shock has been delivered. Normal sensing resumes shortly after shock delivery once physiologic cardiac depolarization has returned. Some devices use true bipolar sensing and integrated bipolar pacing to overcome this limitation. The use of standard sensing protocols applying fixed sensitivity values works well for pacemakers but not for ICDs because of the need to reliably sense and differentiate between varying clinically relevant rhythms such as sinus rhythm, premature ventricular (PVC) beats, and ventricular fibrillation where extreme variation in amplitude of intracardiac electrograms may occur. A fixed sensitivity level would be unable to adapt to these changes. Most ICDs use some variation of automatic sensitivity control, allowing for a “most sensitive value” to be programmed either as an absolute number or as a general term such as “least” or “most” sensitive. After a sensed event, the device reverts to higher sensing threshold in order to prevent T‐wave oversensing or inadvertent oversensing of noncardiac events. The longer the period the device monitors for a sensed event, the more sensitive it becomes. This function provides the ability to determine if the patient has gone into fine ventricular fibrillation that might otherwise be missed if the device was set at less sensitive settings. Figure 11 shows a comparison of the sensing algorithms between pacemakers and ICDs.
(a) True bipolar sensing occurs between the lead tip (cathode) and proximal ring (anode) independent of the defibrillation coil. (b) Integrated bipolar sensing utilizes the lead tip as the cathode and the defibrillation coil as the sensing anode. Sensing is more with a true bipolar configuration.
(a) A typical example of a bipolar right ventricular intracardiac electrogram from a pacemaker. The electrogram peak value is determined and the sensitivity is decreased to a fixed programmed value or a programmed average percentage of the peak value. (b) An example of a bipolar right ventricular intracardiac electrogram from a defibrillator. The electrogram peak value is determined and stored. Then a stepwise decay algorithm is used to the maximum programmed sensitivity. Sensitivity algorithms differ between device manufacturers.
The first step in evaluating pacemaker malfunction is to determine whether the function of the device is truly abnormal [5]. If a pacemaker malfunction has been confirmed, the next step consists of a detailed patient history. The history may provide important clues to the likely diagnosis. If the problem or complaint occurs shortly after device implant, lead dislodgment, loose set screws, misalignment of the lead within the connector block or poor lead placement should be suspected as potential causes [2]. In the acute period, battery depletion or lead fracture is highly unlikely. Conversely, a patient presenting with an older device is more likely to experience lead failure or battery depletion rather than lead dislodgment or connection issues.
A tachycardia driven by the pacemaker presents a more difficult situation. In most cases, application of a magnet or reprogramming the device will terminate the abnormal rhythm. In rare cases, the pacemaker will not respond to these simple measures, and urgent surgical intervention may be required for “runaway pacemaker” (Figure 12). This uncommon malfunction is caused by a major component failure in the pacing circuit. The vast majority of rapid ventricular‐paced rhythms in Dual pacing, Dual sensing, Dual action (DDD) or Ventricular pacing, Dual sensing, Dual action (VDD) devices are due to tracking of atrial fibrillation or atrial flutter. The pacemaker will attempt to track the rapid atrial rate to the programmed upper rate limit (URL) if mode switching is not enabled or fails to respond appropriately. Placing a magnet over the device will drop the pacing rate to the magnet rate of the device until a nontracking mode such as DDI or Ventricular pacing, Ventricular sensing, Inhibited (VVI) is programmed. Sensor‐driven devices may cause rapid pacing as well. After the patient is stabilized, a history is obtained, and the initial device data collected, the 12‐lead surface Electrocardiogram (ECG) should be evaluated. An approach to determine the general function of the pacing system is detailed below:
Pacing
Spike present
Verify appropriate rate interval
Verify appropriate depolarization response
capture
pseudo‐fusion
fusion
Spike absent
Apply magnet (magnet function must be enabled)
(Note: a ventricular pacemaker spike falling in the absolute refractory period of the myocardium will NOT result in capture.)
Observe for pace artifact and capture on 12‐lead surface ECG.
Sensing
Patient must have a nonpaced rhythm
Appropriate escape interval
Compare function to known technical information, watch for end of service indicators and other variations
Runaway pacemaker: this strip shows VVI pacing at 180 bpm (the runaway protect limit on this device). The pacemaker was programmed to the DDD mode with an upper rate limit of 120 bpm. Therapeutic radiation delivered to the pacemaker in a patient with breast cancer resulted in circuit failure and rapid pacing. Even magnet application did not slow the pacing rate.
Oversensing is readily diagnosed by placing a magnet over the device. If the pacemaker was not pacing or paced too slow due to oversensing, pacing will resume once the magnet is in place. If there is no pacing with the magnet on, then either the pacemaker is not putting out a pulse or the pulse is not reaching the heart.
Causes for true pacemaker failure are noted below:
Depletion of the device battery [6]
Defibrillation close to or on top of the device
Device in the radiation field [7]
Devices on recall or alert with known modes of failure [8]
Electrocautery use close to or on the device
Random component failure
Direct mechanical trauma to the device
This potentially life‐threatening problem is identified by the presence of pacemaker pulse artifact without capture in the appropriate chamber following the impulse. Causes of noncapture are listed below [2]:
Exit block (high capture threshold) or inappropriate programming resulting in insufficient output or pulse width
Malfunction or inappropriate programming of automatic capture output algorithms
Lead dislodgment
Lead fracture
Lead insulation failure
Loose lead‐to‐pacemaker connection
Low battery output
Severe metabolic imbalance
Threshold rise due to drug effect
“Pseudo‐noncapture” (pacing during the myocardial refractory period due to undersensing of the preceding complex)
Increase pacemaker output if possible. Where appropriate, revise or replace lead or pacemaker, correct metabolic imbalances. For pseudo‐noncapture adjust the sensitivity to a more sensitive setting, or revise the lead if sensing is very poor. Program to unipolar polarity.
Undersensing is recognized by the presence of a pulse artifact that occurs after an intrinsic event, but fails to reset the escape interval. The pacing output may or may not capture depending on the timing during the cardiac cycle. Causes of undersensing (thus “overpacing”) are listed below [9]:
Poor lead position with poor R‐wave or P‐wave amplitude
Lead dislodgment
Lead fracture
Lead insulation failure
Lead perforation of the myocardium
Severe metabolic disturbance
Defibrillation near pacemaker
Myocardial infarction of tissue near electrode
Ectopic beats of low intracardiac amplitude
Dual pacing, Ventricular sensing, Inhibited (DVI)‐committed function
Safety pacing
Inappropriate programming
Magnet application
Increase pacemaker sensitivity. Where appropriate, revise or replace the lead. Try reprogramming polarity. If the problem is very infrequent then careful observation may be acceptable.
A diagram highlighting the different components of a single‐chamber pacemaker and ICD is shown in Figure 13. In a single‐chamber system, oversensing is recognized by inappropriate inhibition of the pacemaker. Oversensing may result in total inhibition of output or prolongation of the escape interval. Myopotentials are a common cause of oversensing, which is seen predominately in unipolar pacemakers and usually results from sensing noncardiac muscle activity (e.g. pectoralis muscle or abdominal rectus muscles). Myopotentials are triggered by arm movements such as arm lifting in patients with prepectoral implants, or moving from a lying to sitting position in patients with abdominal implants. Oversensing may also occur if the ventricular lead falsely senses the T‐wave. Despite an increase in environmental EMI, pacemakers prove fairly resistant to this type of interference because of continuous design improvements. Sensing intrinsic or extraneous EMI results in the device falsely detecting a cardiac event. The pacing output will be inhibited as long as these interfering signals continue. A dual‐chamber system may track electrical signals such as myopotentials in either the atrium, ventricle or both. The atrial channel is usually set to a more sensitive value than the ventricular channel. Tracking may result from oversensing of electrical signals on the atrial channel, inhibiting atrial output, while these signals are too small to be sensed by the ventricular channel. Each time oversensing occurs on the atrial channel an atrioventricular interval (AVI) is triggered, resulting in ventricular output at a rate up to the programmed upper rate limit (URL). Causes of oversensing are listed below [9]:
Myopotentials
Electromagnetic interference
T‐wave sensing
Far‐field R‐wave sensing (atrial lead)
Lead insulation failure
Lead dislodgement
Lead fracture (Image 1)
Loose fixation screw (Image 2)
Crosstalk
Basic components of a single‐chamber pacemaker (top) and single‐chamber ICD (bottom) (DF4 lead model shown).
Chest radiography demonstrating a lead fracture (arrow) resulting in high lead impedance.
Chest radiography showing two loose set screws (black arrows) resulting in lead noise and high impedance. After pocket revision and proper reconnection of both lead device and lead parameters normalized.
Decrease the sensitivity of the device. For far‐field or T‐wave oversensing, prolongation of the refractory period will also correct the problem. The sensing polarity may be reprogrammed to bipolar if the option is available and the patient has a bipolar lead. In some instances, surgical intervention may be indicated to repair the lead, replace the lead or upgrade to a bipolar system. Loose set screw almost always needs corrective surgery as well as lead dislodgement. Lead fracture, if not complete, can be managed by changing the programming from a bipolar lead to a unipolar, using the functioning lead channel.
Diaphragmatic stimulation may result from inadvertent right phrenic nerve pacing by the right atrial lead or by direct stimulation of the diaphragm or chest wall muscle by the ventricular lead. Extracardiac stimulation occurs due to poor lead placement and/or high output pacing. Lead perforation through the myocardial wall may cause extracardiac stimulation [10]. Unipolar pacemakers and leads with failed outer insulation may trigger stimulation of tissue adjacent to the site of the exposed conductor coil.
Decrease output if possible while maintaining an adequate safety margin for cardiac capture. Revision of the culprit lead may be required. Reprogram to bipolar polarity if unipolar.
Pacemaker syndrome can occur in patients in sinus rhythm who receive a VVI pacing system or in patients with a dual‐chamber device if the atrial lead fails to properly capture or sense [11]. Ventricular pacing asynchronous to atrial contraction will limit the atrial contribution to ventricular filling. The resultant decline in cardiac output may cause patient fatigue and discomfort whenever the pacemaker is pacing. The classic example of pacemaker syndrome is caused by retrograde AV‐nodal conduction. When the ventricle is paced and contracts, the depolarization impulse travels in a retrograde manner up the His bundle through the AV node towards the atrium. The atrium then contracts while the mitral and tricuspid valves are closed due to simultaneous ventricular contraction. The late atrial contraction causes blood to flow retrograde into the venous system resulting in “cannon A‐waves,” dyspnea, hypotension, fatigue or even syncope. The surface ECG can give important clues to the correct diagnosis. In many cases, a retrograde inverted P‐wave is seen embedded in the T‐wave, as a sign of ineffective (as well as detrimental) atrial contraction. Patients with diastolic dysfunction, pericardial disease or loss of ventricular compliance due to hypertension, ischemic heart disease, ventricular hypertrophy or age are more likely to experience pacemaker syndrome.
For VVI devices, reduce the pacing rate or program a hysteresis rate to allow more time in sinus rhythm. If device reprogramming fails to resolve the problem, upgrade to a dual‐chamber pacemaker is indicated. A malfunctioning atrial lead in a dual‐chamber system may either be reprogramed or require surgical correction.
Pacemaker‐mediated tachycardia (PMT), also referred to as endless‐loop tachycardia or ELT, is an abnormal state caused by the presence of an accessory conducting pathway (the pacemaker) [12]. The mechanism of tachycardia is similar to that seen in patients presenting with the Wolff‐Parkinson‐White Syndrome. PMT often begins with a premature ventricular beat that is either spontaneous or pacemaker induced (Figure 14). The electrical impulse traverses retrograde through the His bundle and AV node to the atrium. The pacemaker will sense the retrograde P‐wave if it falls outside of the postventricular atrial refractory period (PVARP). This will trigger an AVI after which the pacemaker will pace the ventricle. This cycle will repeat itself until one of the following occurs: (1) the retrograde P‐wave blocks at the level of the AV node, (2) the retrograde P‐wave falls within PVARP, (3) a magnet is applied to the pacemaker (disabling sensing) or (4) the device is reprogrammed to a longer PVARP or AV interval. The patient may use standard vagal maneuvers to induce transient AV block, thereby terminating the tachycardia. Though not commonly used for this purpose, adenosine (or any other AV‐nodal blocking agent) may be given to terminate the tachycardia. PMT may initiate or restarted if a ventricular‐sensed beat precedes an atrial beat. This includes a PVC, premature junctional beat, loss of atrial sensing or capture, and myopotential tracking or inhibition in the atrium. Appropriate programming of the PVARP will prevent PMT such that any retrograde P‐wave will fall within this interval and therefore not be sensed by the atrial channel. However, some patients have markedly prolonged AV‐nodal conduction and the long PVARP that is necessary to prevent PMT may severely limit the maximum tracking rate of the device due to the resulting long total atrial refractory period (TARP). Most modern pacemakers offer PMT prevention, yet still allow programming a short PVARP. One option automatically extends the PVARP for one cardiac cycle whenever a sensed R‐wave is not preceded by a paced or sensed P‐wave (assuming a PVC). An alternative method is to disable atrial sensing after a PVC is detected. This is also known as “DVI on PVC” since no atrial sensing takes place for one cardiac cycle. When first introduced by Pacesetter, it was known as “DDX” (some of these older devices are still in use today). The newest prevention algorithm will force an atrial output when sensing a PVC. Pacing the atrium at the time of a PVC will result in collision of anterograde and retrograde beats in the AV node, thus preventing the onset of PMT. Finally, most current devices provide an automatic termination algorithm if PMT is suspected. When the pacemaker reaches the upper rate (or a separately programmable PMT detection rate) for a specified number of beats, the PVARP is extended for a single cycle or alternatively a DVI cycle is introduced or atrial pacing is delivered, terminating PMT if present.
Pacemaker‐mediated tachycardia (PMT): a PVC occurs (A) causing the ventricle to contract. The electrical impulse conducts retrograde through the AV node (B) resulting in atrial contraction. The retrograde P‐wave is sensed by the pacemaker, which initiates an AV interval (AVI). At the end of the AVI, a pacing stimulus is delivered to the ventricle (C) and the cycle continues.
Figure 15 shows two different scenarios when atrial tachycardia (AT) can be misdiagnosed as pacemaker‐mediated tachycardia (PMT).
An AT at a rate below the upper tracking limit is sensed on the atrial channel triggering an impulse on the ventricular channel.
Pacing in the atrial channel can suppress or terminate AT.
Prolonging the PVARP may lead to 2:1 atrioventricular conduction without interrupting the AT.
In true PMT, ventricular activation causes retrograde atrial activation which is sensed on the atrial channel triggering ventricular depolarization.
Pacing in the atrium during PMT interrupts the tachycardia but cannot differentiate PMT from AT (see [2])
Prolonging the PVARP will result in termination of PMT with resumption of sinus rhythm, while an underlying AT will conduct to the ventricle at exactly half the tachycardia rate.
Differentiating atrial tachycardia (AT) from pacemaker‐mediated tachycardia (PMT)—see the text for details.
In conclusion, prolonging the PVARP is a better method to differentiate AT from PMT and effectively terminate PMT.
This is a potentially dangerous or lethal problem in patients who are pacemaker dependent [2]. Crosstalk occurs if the ventricular sensing amplifier misinterprets the atrial pacing impulse for an intrinsic ventricular beat. Ventricular output is inhibited and in patients without a ventricular escape rhythm, asystole will occur. On the surface, ECG crosstalk results in paced atrial P‐waves without subsequent ventricular output. As a characteristic finding, the atrial pacing interval is equal to the atrial escape interval (AEI), rather than AVI and AEI combined. The shortened pacing interval results because the AVI is terminated prematurely due to the ventricular circuit falsely identifying the atrial pacing pulse for an intrinsic ventricular beat resetting the pacemaker to the next cycle. However, in a device using atrial‐based timing, the AVI will be allowed to complete before the next AEI ensues, thus maintaining the programmed pacing rate. Crosstalk is more likely to occur if high atrial output pacing is combined with very sensitive settings on the ventricular channel.
Most modern pacemakers are very resistant to crosstalk and certain features can prevent or reduce the effect of crosstalk. “safety pacing,” also known as “ventricular safety standby” or “nonphysiologic AV‐delay” ensures a brief period of ventricular sensing during the early postatrial output period. This special sensing interval immediately following the ventricular blanking period is known as the “crosstalk‐sensing window” (CTW). An event falling into the CTW may be the result of crosstalk or of true ventricular origin. If the ventricular lead senses an event during the CTW, a ventricular pacing output is committed at a short AV‐delay (usually 100–120 ms), providing ventricular rate support should crosstalk be present. In the presence of a PVC or other intrinsic beat, use of a short AV‐delay ensures that the ventricular output is not delivered during the relative refractory period (vulnerable period) of the T‐wave (Figure 11a). While this feature will avoid the detrimental effects of crosstalk, the underlying cause needs be identified and corrected as soon as possible.
Figure 16 represents an example of crosstalk: the atrial impulse delivered by the pacemaker is sensed on the ventricular channel resulting in inhibition of a ventricular output. In summary, the management of crosstalk includes:
Decreasing sensitivity of the ventricular channel
Decreasing output of the atrial channel
Activating ventricular safety pacing
Increasing the ventricular blanking period
Decreasing atrial pulse width
If the cause of crosstalk is insulation failure, implantation of a new atrial lead is warranted.
Crosstalk: atrial activation is sensed on the ventricular channel resulting in inhibition of ventricular pacing.
Failure of the ICD to deliver a shock during ventricular tachycardia or ventricular fibrillation may result in presyncope, syncope or death. Conversely, inappropriate shock therapy causes patient discomfort, increases health care expenditure due to device clinic visits and/or hospitalization and heightens mortality [13]. Since all commercially available ICDs provide anti‐bradycardia pacing their use is subject to the same potential problems as regular pacemakers. In addition, the dedicated bipolar ICD lead is used for tachycardia detection and treatment. In an “integrated bipolar” system, one of the shocking electrodes has the added function of a sensing and pacing anode. The ICD gathers information on the low‐voltage impedance of the pacing system and the high‐voltage impedance during shock delivery. The ability to evaluate the low‐ and high‐voltage components separately can help the physician localize the site of lead failure. Adding a separate pacing/sensing lead may be a simple solution when only the low‐voltage conductor is affected. However, failure of the high‐voltage component often requires lead extraction and replacement. In certain circumstances, a second shocking coil may be added without removing the malfunctioning lead. The approach to the patient with suspected ICD malfunction is essentially the same as the approach described for the pacemaker patient. Gathering patient data, understanding the indication for device implant, ICD interrogation, and evaluating the circumstances surrounding the incident in question are all essential. A common clinical scenario is the need to assess whether an ICD shock was appropriately delivered. For ICDs with limited diagnostic capability, elucidating the history surrounding the shock is crucial. The delivery of an appropriate ICD shock is often preceded by palpitations, lightheadedness, dyspnea or syncope. However, even in the absence of aforementioned symptoms, an appropriate ICD shock may have been delivered. Symptomatic hypotension may not ensue if the patient is in a sitting or supine position. Alternatively, the patient may simply not recollect the event due to insufficient brain perfusion or the patient was asleep at the time of the arrhythmic event. Indeed, nocturnal myoclonus is frequently misinterpreted by the patient’s spouse as a device discharge. Inappropriate ICD shocks most commonly occur in the setting of AF. In the setting of AF with a ventricular response rate that exceeds the detection rate of the device, the ICD will charge and deliver one or repetitive shocks. Occasionally, the shock will convert AF to sinus rhythm. Dual‐coil ICD leads with the proximal coil located within the right atrium are more likely to convert AF to sinus rhythm than single‐coil leads. Importantly, these shocks are not the result of device malfunction, but rather due to an undesirable patient‐device interaction. The specific categories of device malfunction are noted below.
Failure of the ICD to deliver anti‐tachycardia therapy may be lethal. The reasons for failure to shock are listed as follows [14]:
Undersensing
Lead malposition
Lead dislodgment
Lead perforation
Lead fracture
Lead insulation failure
Lead‐to‐device connector problem
Sensitivity set too low (i.e. insensitive)
Poor electrogram amplitude due to change in myocardial substrate
Myocardial infarction
Drug therapy
Metabolic imbalance
“Fine” ventricular fibrillation
Primary circuit failure
Battery failure
Shock therapy turned off (by programming or magnet)
Magnet placed over the device
Strong magnetic field present
Detection rate set too high
Failure to meet additional detection criteria
Rate stability
Sudden onset
Morphology criteria
Slowing of tachycardia below detection rate
Substrate changes
Metabolic changes
Electrolyte changes
Drug therapy changes
Interaction with permanent pacemaker
Lead failure or programming the rate detection zone too high is the most common reason for failure of the ICD to deliver therapy. The cause for lead failure may be identified on fluoroscopy. As older transvenous ICD leads are substantially thicker than conventional pacing leads, they are exposed to higher forces below the clavicle when using a subclavian vein access. Lead fracture typically affects one of the inner conductors of a coaxial or triaxial lead. Sometimes an intact outer conductor shielding a fractured inner conductor complicates proper diagnosis on fluoroscopy. Fractures can result in two broken ends remaining in intermittent contact. Several fluoroscopic projections may be required to visualize conductor failure and a slightly over‐penetrated fluoroscopic image with settings similar to a dedicated thoracic spine view should be used. Fractures and insulation failures are more likely to occur after 1 or more years. If undersensing develops within 30 days of ICD implant, lead malposition, lead dislodgment or lead perforation need to be considered. Rarely, a loose connection between a connector pin and a connector block is the cause for ICD failure. Although ICDs are generally very reliable, a number of alerts have been reported for different models. Circuit failure, software lock‐up, and other problems do occur infrequently and proper device interrogation will usually not be possible if any of these situations are present. In some cases, a “system reset” may be able to resolve the problem. In other cases, a software patch downloaded to the device will correct the problem.
Patient noncompliance with routine device clinic follow‐up may result in ICD failure due to battery depletion. The ICD may become nonfunctional or lack sufficient power to charge the capacitors to the required voltage for discharge. Most ICDs restrict the time allowed for the capacitor to charge. Should the battery reserve be too low or the capacitor be defective (a common problem in earlier devices), the charge time may exceed the maximum time allowed and the ICD will not deliver a shock.
Occasionally, the rate detection zone is set too high. This may result from inappropriate programming or more commonly initiation of antiarrhythmic drug therapy such as amiodarone or sotalol. Antiarrhythmic drugs may cause slowing of the ventricular tachycardia cycle length below the programmed detection rate [15]. Significant metabolic or electrolyte abnormalities can affect the tachycardia cycle length, but may also alter the signal amplitude resulting in undersensing or failure to detect. Use of additional detection criteria to enhance specificity may delay or prevent appropriate ICD therapy and should be applied cautiously. Tissue injury due to myocardial infarction may lead to significant changes in the intracardiac electrogram and failure to sense.
Asynchronous pacing can be seen if bradycardia backup‐pacing is turned on. In the past, many patients requiring pacing support underwent additional pacemaker implantation to prevent early ICD battery depletion from frequent pacing. This is usually of no clinical consequence unless the ICD senses the pacing output delivered by the pacemaker. In a worst‐case scenario, the pacemaker may misinterpret ventricular fibrillation for asystole and attempt to pace fibrillating myocardium. If the ICD were falsely interpret the pacing impulse from the pacemaker for a regular Waveforms of ventricular depolarization (QRS) complex, device therapy may be withheld indefinitely. For this reason, special care is exercised if a pacemaker patient undergoes additional ICD implantation or a dedicated pacemaker is indicated in an ICD patient. Be aware that, albeit less likely, oversensing of the atrial pacemaker impulse by the ICD may lead to similar grave consequences.
Defibrillator lead‐related problems virtually always require surgical correction. Most physicians argue that lead failure requires lead removal due to the large size of the lead and potential interaction with a newly placed lead. A recently implanted ICD lead that has dislodged or demonstrated poor sensing performance may be repositioned if lead integrity can be verified. Immediate device replacement is indicated in the case of battery depletion or if a nonfunctional ICD fails software reset. Simple reprogramming of the ICD will resolve problems related to inappropriate tachycardia detection zones or if too many specificity criteria are applied to diagnose ventricular tachycardia causing delay or failure to deliver appropriate therapy. Interaction with a permanent pacemaker may be eliminated by reprogramming the pacemaker output and pulse width to lower values. Only a bipolar pacemaker should be implanted if an ICD is already present. Furthermore, the pacemaker should be a dedicated bipolar device or allow bipolar pacing as the “power‐on‐reset” polarity. The latter will prevent reset to unipolar polarity and guarantee pacing in the bipolar mode if power is temporarily interrupted. Since current ICDs integrate full‐featured pacing capabilities, a separate pacemaker is rarely indicated. Noise due to lead fracture can cause oversensing with inhibition of output. Acute management includes changing to a unipolar configuration or sensing from a wider antenna, for example, lead tip to right ventricle (RV) coil, until the lead can be replaced.
Despite proper detection and appropriate ICD therapy, some arrhythmic episodes may fail to convert to sinus rhythm with potentially lethal consequences for the patient. Below is a list of problems that may prevent restoration of sinus rhythm despite appropriate ICD therapy [15]:
High defibrillation threshold
Poor cardiac substrate (fibrosis, scar, etc.)
Acute myocardial infarction
Metabolic abnormality
Electrolyte abnormality
Drug therapy
Drug proarrhythmia
High‐voltage lead fracture
High‐voltage lead insulation failure
High‐voltage lead migration
Inappropriate device programming
Low (inadequate) shock energy
Ineffective polarity
Sub‐optimal “tilt”
Ineffective pacing sequence
Pacemaker polarity switch
Atrial arrhythmias
Sinus tachycardia
“VT Storm”
Changes to the myocardial substrate following successful ICD implantation may result in delayed or unsuccessful antiarrhythmic therapy. Acute myocardial infarction, severe electrolyte or metabolic imbalance or initiation of antiarrhythmic drug therapy may increase the defibrillation threshold. Amiodarone is frequently utilized in patients presenting with life‐threatening arrhythmias and may increase the defibrillation threshold. Some patients will require defibrillation threshold testing after amiodarone initiation to verify successful conversion with ICD shock delivery. Other drugs may act proarrhythmic to the effect that the arrhythmia fails to convert or resumes immediately after conversion. Lead fracture or insulation failure will reduce the actual amount of energy delivered to the heart and may impact the delivery of an effective ICD shock. Lead movement may alter the shock vector resulting in suboptimal current flow between anode and cathode.
Programming the shock energy below maximum output will conserve battery life, allow quicker shock delivery, and cause less pain to the patient. However, an insufficient safety margin between defibrillation threshold and applied energy reduces the probability of successful conversion. The shock duration (pulse width) is programmable on some devices and set automatically on others. If set too short or overly long, defibrillation will be unsuccessful. The optimal shock duration varies based on the resistance. The positive and negative phases of the shock wave may be programmable in duration and can significantly affect efficiency of therapy. Furthermore, anti‐tachycardia pacing or low‐energy shock delivery may accelerate ventricular tachycardia or cause degeneration into ventricular fibrillation.
Immediately correct reversible metabolic, drug or electrolyte abnormalities. Lead or device problems will often require surgical revision. Reprogram ICD to a different rate detection zone and/or reassess additional criteria applied for tachycardia recognition. Atrial arrhythmias may require drug therapy, catheter ablation to definitive treatment of the clinical arrhythmia or ablation of the AV node. Appropriate pacemaker selection and programming are mandatory if separate devices are used in the same patient. Strongly consider replacement for a single device.
Inappropriate ICD shocks are far more common than failure to convert or failure to deliver therapy. Patients may think an ICD shock was delivered inappropriately, while thorough evaluation of telemetry data and stored electrograms confirms proper device therapy. If the ICD shock was determined inappropriate, the triggering event needs to be elucidated and corrected quickly. Repeat ICD shocks are poorly tolerated by the conscious patient because of pain encountered and fear of future episodes. The patient may voice anger and frustration or demand device removal. Although inappropriate shocks are less likely to result in patient death, immediate diagnosis and correction of the underlying cause are warranted. Causes for inappropriate ICD therapy are as follows [16]:
Oversensing
Electromagnetic interference
Interaction with another implanted device
Lead fracture
Lead insulation failure
Loose connections
Myopotentials
T‐Wave oversensing
Pacing impulse from permanent pacemaker
“Y” adapted biventricular adapters and connectors
Detection rate set too low
Supraventricular arrhythmias
Paroxysmal supraventricular tachycardia
Atrial fibrillation
Atrial flutter
Sinus tachycardia
Inappropriate shocks are most commonly encountered in the presence of atrial fibrillation. Many patients who undergo ICD implantation demonstrate enlarged hearts predisposing them to atrial tachyarrhythmias. Patients with a history of slow ventricular tachycardia may experience overlap with sinus tachycardia at the lower rate limit of the detection zone. This may occur during exercise, sexual intercourse or emotional stress and result in ICD shock. Oversensing may lead to inappropriate detection as detailed above. Interactions may result from separate pacemaker and ICD implantation in the same patient. In the presence of a unipolar and some bipolar pacemakers, the ICD may sense the ventricular and/or atrial pacing spike resulting in double‐counting of the ventricular rate during VVI pacing or triple‐counting of the ventricular rate during DDD pacing. Double‐sensing may also be seen with some biventricular devices if the right and left ventricles are wired into the same sensing circuit, for example, when using a “Y” adapter on the pacing lead to connect to a single ventricular connector on the device. It may also be the result of an older ICD design where, despite separate connectors available for the RV and left ventricle (LV) lead, the leads are interconnected within the device and run through a single pace/sense circuit. The net result of both of these configurations is the same, with the RV and LV lead being sensed on the same channel. Double‐counting may occur due to the long conduction delay between RV and LV if the patient has a heart rate in excess of the URL, or one of the leads fails to capture.
The ICD detection rate should be increased if the sinus rate overlaps with the lower rate limit of the detection zone. Beta‐blocker therapy should be initiated or uptitrated to reduce the sinus rate. Furthermore, additional discrimination criteria such as sudden onset, rate stability, and QRS morphology should be activated. Catheter ablation to treat the clinical atrial arrhythmia or ablation of the AV node may be an option in select patients. Interaction between pacemaker and ICD will require reprogramming to a lower output and pulse width, using bipolar polarity or upgrading to an integrated pacemaker and ICD system. The latter is often necessary if double‐sensing occurs while using retained older leads or ICD connector designs. In some situations, the pacing lead may require repositioning. Lead failure and connection problems will often require urgent surgical correction. If EMI is detected, the patient should be advised to avoid the source of interference. For some patients, this may involve reassignment of duties at work or even a change in employment. Most ICD malfunctions and pseudo‐malfunctions are readily diagnosed after obtaining a careful patient history, use of fluoroscopy, and device interrogation. Unnecessary replacement of the ICD will be avoided and patient safety and comfort assured if competent personnel addresses the device problem in a consistent manner.
In order to troubleshoot implantable cardiac devices, the clinician should have a thorough understanding of the underlying physics and signal processing techniques. Device implantation and follow‐up requires knowledge of the most common causes for device malfunction. While device reprogramming may offer a permanent solution for some pacemaker or ICD malfunctions, others will require surgical correction as appropriate first‐line therapy.
The correct management of craniofacial differences (CFD’s) -including cleft lip with/without cleft palate (CL ± CP)- is still a challenge for clinicians treating such conditions, due to its treatment length and the different aspects that have to be holistically addressed in accordance with overall and craniofacial growth and development, speech and hearing, facial esthetics, and psychological self-perception of patients with such characteristics.
Although a universal treatment protocol has not been agreed among craniofacial teams worldwide [1], several parameters of evaluation and treatment have been set and reviewed periodically, following the recommended practices for the care of patients with craniofacial differences made by the ACPA (American Cleft-Palate Craniofacial Association) [2] (revised in 2018), based on the call of the Surgeon General of the United States on the needs for children with special health care [3]. A summary of such parameters appears below:
(a) The interdisciplinary team management of patients with craniofacial differences is essential; (b) Clinical expertise in diagnosis and treatment and optimal care for these patients is provided by teams with enough exposure to these patients each year; (c) The first evaluation is within the first few days or weeks of life (ideal), but referral for team evaluation and management is appropriate at any age; (d) Since the beginning, the family of a child with a craniofacial difference must be assisted in adjusting to the birth and consequent demands and stress of having a child with CFD; (e) Responsible adults must receive information about treatment procedures, options, risk factors, benefits, and costs to take informed decisions on the child’s behalf, and to prepare the whole family for all recommended procedures. The family (and patient, when is mature enough) participation and collaboration in treatment planning should be actively asked; (f) Team recommendations are basic to develop and implement treatment plans; (g) Complex diagnostic and surgical procedures should be restricted to centers with experienced health professionals; (h) Each team must be sensitive to linguistic, cultural, ethnic, psychosocial, economic, and physical factors affecting the relationships among the team, the patient and family; (i) Longitudinal follow-up of patients, including appropriate documentation and record-keeping is essential to monitor both short-term and long-term outcomes and falls under the responsibility of each team; (j) The effects on growth, function, appearance satisfaction and psychosocial well-being of the patient should be considered when performing evaluation of treatment outcomes.
Following these parameters, this chapter explain in detail our craniofacial orthodontics treatment algorithms for the patient with unilateral cleft lip and palate (UCLP) from mixed dentition onwards, which addressed all topics related with diagnosis and treatment planning for adolescents and young adults affected with this craniofacial difference.
Mars et al. in 1987 introduced the GOSLON yardstick [4], which has become the standard diagnostic tool for patients with UCLP worldwide. Ozawa et al. in 2011 expanded the same classification for bilateral clefts [5]. This classification, based on dental casts, has proven to be a good and simple option to grade the malocclusion present and to give some hints on the level of difficulty in its correction. Other broader approaches -such as the original Huddart-Bodenham classification (used in deciduous dentition only) [6], or its modification used in both deciduous and permanent dentitions (proposed by Mossey et al. [7])-, are also other interesting approaches to classify all dental components present in UCLP and BCLP malocclusions. However, those indexes missed a common aspect that cannot be forgotten in a craniofacial orthodontic evaluation: the facial pattern in three dimensions that could worsen (or improve) the existing CL ± CP condition. The GOSLON does not consider frontal and lateral facial photographs or cephalometric radiographs, which are regular diagnostic records in orthodontics (taken digitally for these patients in the XXI century). These records are important to detect left-to-right bone vertical discrepancies that could make some UCLP cases more difficult to correct properly than previously thought. This is the reason why the orthodontic diagnosis (and its indicated treatment) cannot be established solely from study dental models. The GOSLON yardstick can be used as a classification system, but not as a determiner of treatment complexity without considering the 3D facial aspects of a complex malocclusion.
Having as a start point the GOSLON yardstick, our unit has developed a modified GOSLON yardstick (named GOSLON+), based not only on dental casts but also on frontal and facial digital photographs and radiographs. These records can be used to accurately determine the involvement of craniofacial orthodontics and craniofacial surgery in the resolution of unilateral (and bilateral) cases, depending on the degree of asymmetry associated with the cleft, following all aspects involved in a complete orthodontic diagnosis. The following diagram and the accompanying patients’ photographs (with full records) demonstrate our current diagnosis categories and changes in the treatment of patients with UCLP (modified from the original GOSLON) (Table 1, Figure 1), [4] Our modified classification considers the influence of facial and occlusal 3D aspects in the craniofacial overall diagnosis and the need for additional treatment created by the existing frontal asymmetry.
Group | Characteristics | Treatment | Prognosis |
---|---|---|---|
1± |
| Surgical orthodontics and surgical treatment for class II malocclusion. | Good/Fair (Depending of Degree of Facial Asymmetry [+]) |
2± |
| Surgical orthodontics and surgical treatment for moderate or complex class I malocclusion. | Excellent (None [−] to some Degree of Facial Asymmetry [+]) |
3± |
| Surgical orthodontics and surgical treatment for mild class III malocclusion. | Good/Fair (Depending of Degree of Facial Asymmetry [+]) |
4± |
| Surgical orthodontics and surgical treatment for severe class III malocclusion. | Fair (Depending of Degree of Facial Asymmetry [+]) |
5± |
| Surgical orthodontics and step-wise surgical treatment for extreme class III malocclusion. (Maxillary Osteogenic Distraction and Orthognathic Surgery). | Fair (Depending of Degree of Facial Asymmetry [+]) |
Modified GOSLON yardstick (GOSLON+) for patients with UCLP. A similar table apply to patients with BCLP.
Facial and intraoral characteristics of patients presenting the five different degrees of GOSLON+ yardstick. Observe that treatment prognosis further decreases when frontal and lateral facial photographs are included in the treatment algorithm to manage successfully the existing alveolar clefts.
It is well known that not all clefts are similar [6, 8, 9, 10, 11]. Moreover, patients affected by UCLP have some degree of facial asymmetry that affects the prognosis (Figure 1). This fact must be considered within the orthodontic-surgical diagnosis. Accordingly, their ortho-surgical treatment plan should not be the same either, due to the type and extension of cleft, the timing for the initiation of those treatments, and the individual needs for surgical treatment influencing the selection of surgical techniques. In addition to these factors that have a negative influence on facial growth, the expertise of the ortho-surgical team and the interdisciplinary management given to the patient is the last -but not the least- item to be considered for obtaining a satisfactory treatment outcome [12].
Based on this improved GOSLON classification, a description of the surgical orthodontic management for average and wide clefts will be addressed. After that, two different surgical orthodontics algorithms will be presented, with clinical cases to summarize the decision-making process applied in the surgical orthodontic care of patients with UCLP with different degrees of sagittal and transversal maxillary-mandibular involvement in the Clínica Noel Foundation at Medellin, Colombia, S.A.
The alveolar cleft -the space between the maxillary segments anterior to the incisor foramen- represents a lack of continuity of both maxillary dental arch and basal bone. Spatially, it can be represented as a pyramid placed on its side, with its base towards the labial side and its apex located in a posterior and superior position inside the cleft maxilla [13]. This gap should be ideally filled by a cancellous bone graft to restore its basal and alveolar normal architecture. This defect gives origin to a particular kind of critical-size segmental defect that creates a significant challenge for craniofacial surgeons, maxillofacial surgeons and craniofacial orthodontists [14].
From all the alternatives to fill completely the maxillary cleft, the secondary (intermediate or late) alveolar bone grafting (SABG) is still the gold standard treatment to restore the alveolar anatomy, either in mixed dentition or early permanent dentition [15]. The objectives of SABG include (1) to restore and stabilize the normal architecture of the maxilla; (2) to allow eruption of permanent lateral incisor and canine; (3) to provide support and elevation of the affected wing base; (4) to close present oronasal fistulas and (5) to provide “adequate” bone support to be restored later with prostodontics with/without dental implants, in case that a closure of the gap with dental eruption cannot be achieved [16, 17]. It has been our approach to limit its objectives to the first three in mixed dentition patients, due to the uncertain nature in time of this type of autografts and the impediment for free dental movement created by cortical grafts at early ages. However, two controversies proposed by Vig still remained valid today: which is the best bone graft type and the best donor site for harvesting? and what is the best timing for maxillary (dento-alveolar) expansion in patients requiring SABG [17]? A third controversy refers to whether the alveolar cleft can be repaired by a combination of bio-engineering alternatives currently available nowadays. Our treatment rationale tries to solve the first two questions as follows:
Several aspects have to be considered for obtaining a successful bone graft in such patients:
During mixed dentition stage, orthodontic treatment can be used previous to surgical treatment to increase maxillary dental arch width and length using the Quad-Helix [18, 19, 20, 21] (Figure 2). This appliance -developed by Ricketts while he was part of the Cleft Palate Clinic at UIC (currently the UIC Craniofacial Center) [22] and improved by Wilson and Wilson in the 80’s [20] and others- is currently applied to correct the collapse of the lateral maxillary segment behind the protruding premaxillary process [23]. In patients with UCLP, the bony palate anatomy presents a primary unilateral deficiency worsen by contraction of scar tissue, as a result of the neonatal surgical palatal closure [19, 23]. In addition to the dento-alveolar effect obtained in patients without clefts, the main bony effect of the Quad-Helix in UCLP cases is the expansion of the lateral maxillary shelves when the de-rotation of the maxillary molars is achieved [19, 23]. In such cases, dento-alveolar expansion before surgery results in similar treatment outcomes than in patients with maxillary expansion [24], with the benefit of working with minimum risk of creating secondary maxillary fistulas. Dento-alveolar expansion could also be obtained by other orthodontic appliances such as the reverse Quad-Helix (with poor correction of the molar rotation) [25], conventional or modified jointed fan (or butterfly) expander [26, 27, 28], NiTi palatal expander [29], or self-ligation appliances [30].
Recovery of normal transversal maxillary width with correct maxillary alignment after the use of Quad-Helix. a. Before Quad-Helix, b. At removal time. Notice the change in the cleft architecture and the creation of alveolar spacing for the alignment of the right maxillary canine.
Dento-alveolar maxillary expansion is usually followed by maxillary dentition segmental leveling and alignment (using an anterior [3*2] utility arch) [21, 31, 32, 33, 34]. In order to obtain similar results than those achieved using an inverse treatment protocol (alveolar grafting followed by orthodontics with maxillary expansion) [24], an orthodontic approximation of maxillary segments using a sectional arch approach -after obtaining proper maxillary width but before surgery- should be considered. In older patients, a mini-screws based molar distalization plus orthodontic dental retraction -by controlling the mesial inclination of the canine for greater bone approximation- is often required to create an alveolar defect with parallel walls to minimize the alveolar gap size when a segmental surgery is planned (Figure 3) [35, 36].
Modified First-Phase Orthodontic Strategies. In addition to the a. maxillary utility arch, two other strategies have been useful in the correct alignment of the maxilla prior to surgery: b. sectional approximation of maxillary segments; and c. mini-screw based distalization.
The suggested order of orthopedic-orthodontic procedures would be as follows: 1. Dento-alveolar maxillary expansion; 2. Maxillary segmental dental leveling and alignment; 3. Mini-screw based molar distalization (if needed in patients that have passed the appropriate timing for grafting) and 4. Orthodontic approximation of maxillary segments.
At the time of bone grafting, many craniofacial centers around the world use SABG during mixed dentition (5 to 12 years of age) before or during permanent canine eruption, taking advantage of the growth potential of the maxilla at this stage [37]. In our center, we use Intermediate or late SABG during mixed or early permanent dentition for GOSLON1–3 patients only. We usually perform such procedure in agreement with dental age characteristics of teeth around the cleft (permanent canine and lateral incisor when present). The ideal age range for surgical procedure should be when the canine on the cleft side is from less than 5 mm of its eruption place to a partially erupted canine (1/3 to ½ of crown visible). Late SABG cases with narrow alveolar clefts at the right age allows to work with bone graft stimulation (either with compression osteogenesis or RPE) to obtain excellent results in both cases (Figure 4) [24, 37]. Using SABG as an alveolar bone matrix, we achieve high degree of success in correcting the canine eruption and migration pathway [38]. The bone graft would give temporary bone support for the eruption of lateral incisor and/or canine without affecting the growth of the midface, with good outcomes similar to other centers in the world when compared with gingivoperiosteoplasty [21, 39]. Ideally, a complete closure of the space with no need for lateral incisor prosthesis is achieved when the migration of the canine occurs.
Intraoral Results of Iliac Crest Late Secondary Alveolar Bone performed at the Correct Time. a. Despite the fact that all teeth around the cleft were erupted at the initial evaluation, the patient still had intermediate mixed dentition and remaining eruption potential in the lateral incisor adjacent to the alveolar cleft; b. After late SABG and finishing restorative dentistry procedures. Note the closure of the alveolar cleft and the normal gingival architecture obtained by the application of orthodontic compression osteogenesis after cancellous iliac bone grafting.
In chosen candidates, cancellous iliac crest bone from the inner anterior portion of the crest is usually required to close mild-to-moderate type of fistulas (patients with UCLP GOSLON1 to 3 at the appropriate age) (Figure 4). This approach is used to restore momentarily alveolar bone continuity needed for dental movement [40, 41]. Figure 4 shows a case with such approach, with an excellent outcome. However, other harvesting sites such as tibia, mandibular symphysis or retromolar area can be successfully used for this purpose [23, 42, 43].
Of all types of bone graft (cortical, cancellous, or mixed), the fresh autogenous cancellous bone is the “ideal” source for reconstruction of bone integrity, due to the fact that it provides living bone cells and is immune-compatible enough to allow osteogenesis and full integration with the maxilla [40]. Autografts have as its main characteristic osteoproduction [44] -bone growth obtained from combined properties of osteoinduction (recruitment, proliferation, and transformation of osteoprogenitor MSC’s into osteoblasts) [45], osteopromotion (process of secondary support of bone healing and tissue regeneration, without capability of initiate bone formation) [46], osteoconduction (process of osseous and vascular cell ingrowth inside the 3D matrix scaffolding) [47], and “relative” osteogenesis (process of deposition of newly formed bone by osteoblasts at the fracture site)- that enhance osteoprogenitor MSC’s response according with autologous graft type. Allografts also share other advantages such as biocompatibility, and mechanical resistance vs. orthodontic remodeling depending on the graft source [48]. Iliac crest site morbidity, accessibility, and availability of areas of graft harvesting of other donor places create a supposedly difficulty that could be overcome with sufficient surgeon’s exposure to this approach [49] in a capabilities-based curriculum [50]. When a successful incorporation (or modeling) of a graft is achieved, the term osseointegration can be used under this definition (Figure 4) [51]. An optional surgical procedure for treating wide alveolar clefts will be described later.
At the Pre-surgical Planning Time of Post-Surgical Procedures. In cases where lateral incisor in the cleft area is partially missing, split in two by the cleft (creating two “real” supernumerary teeth), or absent, all options involved in the dental restoration of the patient must be considered:
When the lateral (and central incisor or canine, depending on the location of the cleft) present a missing portion, a composite restoration could be required either during or once the orthodontic treatment is finished to improve esthetic appearance (Figure 4).
Lateral incisor supernumeraries present additional difficulties to be addressed: their crowns usually are of decreased size, and the roots are short and with many irregularities and dehiscenses along the root length. Performing restorative procedures, such as extensive composite restauration on the wider tooth, are in order if the chosen supernumerary has its root firmly embedded in bone and the final orthodontic placement of the tooth leaves the root with enough alveolar bone on both sides.
If the lateral incisor is missing, an option would be to take advantage of performing an intermediate SABG followed by the mesial eruption of the canine. Later on, restorative procedures in conjunction with orthodontics will convert the canine anatomy in lateral anatomy, although some differences between normal and converted teeth remain regarding color and crown emergent profile from gingiva (Figure 5).
Intraoral Results of Guided Migration of Permanent Canine through SABG performed at the Correct Time. After successful SABG, the left maxillary canine was directed to erupt in a mesial position from its initial site. Note the hypertrophic gingiva surrounding the teeth on the repaired cleft site. The patient will require cosmetic dentistry procedures in addition to the correct bucco-lingual root torques delivered by the use of lower first bicuspid brackets on the maxillary canine (to act as lateral incisor) and first bicuspid (to act as canine). Protraction of the upper first molar to obtain a well-established class II relationship is under way.
Orthodontic procedures (regarding bracket type and bracket positioning -proper height and buccal-lingual crown inclination of canine and first bicuspid on the cleft side), periodontal procedures (to maintain or recover -partial or totally- the periodontal anatomy affected by decreased gingival thickness as a consequence of mesenchymal deficiency in patients GOSLON3+, 4, 4+, 5 and 5+) (Figure 6) and/or additional cosmetic dentistry/prosthodontic procedures (to transform with such strategies the maxillary canine in lateral incisor and the maxillary bicuspid in canine, and perform additional restorative work if needed) are necessary after SABG surgical procedure for an adequate dental characterization with good-to-fair periodontal condition (Figures 7 and 8). Optional plastic surgery procedures could be needed as well.
Periodontal Results of Connective Tissue Graft and Enamel Matrix Protein Application after Ortho-Surgical Procedures. This experimental procedure in cleft patients allow the clinicians working in poor anatomic conditions -due to the negative influence of a mesenchymal deficiency- to partially recover gingival architecture at the short-term follow-up. Long-term follow-up will give us answers regarding the success of the obtained periodontal stabilization. a. Initial intraoral left close-up photo. The patient has a wide left alveolar cleft with dental inclination of left permanent central incisor (moderate), and left permanent canine (severe); b. Intermediate intraoral left close-up photo. After a segmental maxillary advancement, moderate loss of periodontal attachment and apical migration of gingival margins was observed; c. After connective tissue graft plus enamel matrix protein infiltration. Notice the gain on gingival margins and periodontal thickness as a result of this approach; Surgical sequence: d. Harvesting of palatal connective tissue graft; e. graft waiting to be inserted below gingiva; f. Graft placement under keratinized gingiva; g. Emdogain® syringe used in this case.
Patient with UCLP GOSLON2 treated at Mixed Dentition stage. Initial records: a. Frontal facial photograph; b. Periapical radiograph of the alveolar cleft; c. Intraoral frontal view; Final records: d. Frontal facial photograph; e. Periapical radiograph of the alveolar cleft; f. Intraoral frontal view. The application of the compression osteogenesis strategy was fundamental to obtain normal periodontal architecture in the grafted area of the alveolar cleft.
Patient with UCLP GOSLON2 treated at Permanent Dentition stage. Initial records: a. Frontal facial photograph; b. Intraoral frontal view; Final records: c. Frontal facial photograph; d. Intraoral frontal view. A relatively normal dental and gingival architecture was obtained after the surgical management of a Two-piece LeFort I.
Our retention protocol for patients with normal skeletal relationships (GOSLON2 and 2+) or with mild skeletal discrepancies (GOSLON1, 1+ and 3) use Essix-type retainers. As our treatment approach is directed to obtain a maxillary arch without dental spaces if possible, we seldom use wrap-around maxillary retainers with dental temporary replacements. Our countdown-to-retention includes periodontal evaluation and treatment in patients with GOSLON3+ and more, to address the thin and receding gingiva in cleft-adjacent teeth, associated with genetically-driven periodontal ligament loss described previously (Figure 6). In those cases (which have received correction of existing moderate to severe skeletal discrepancies previously), a periodontal connective tissue graft plus dentin matrix protein injections to increase gingival volume and tissue support, and a dual retention strategy with an additional bonded lingual retainer in the maxillary anterior teeth is used.
Young patients affected by UCLP who have severe restriction of maxillary growth and wide oronasal fistulas (GOSLON4, 4+, 5 and 5+), or adult patients with UCLP in all categories of the GOSLON+ yardstick, have been historically (and unsuccessfully) treated using alveolar bone grafting (secondary or tertiary). In addition, inadequate closure of primary incisions, post-operative wound dehiscence and infections could potentially make bone grafting healing worse [35]. Mars et al. recognized that unilateral alveolar bone grafting success was limited to young patients with “average” maxillary growth (patients GOSLON1, 1+, 2, 2+, and 3) and normal gingival thickness compared with an age-matched normal population [4]. What was the problem? They found out that with increased limitation in maxillary craniofacial growth in patients with UCLP, there was an important compromise in making the maxillary segments meet closely to complete a successful bone graft and a greater difficulty to obtain a fair maxillary dentition by subsequent orthodontic treatment [4].
In order to obtain a surgically-created one-piece maxilla [52], craniofacial centers worldwide use strategies based on segmental maxillary advancements (described by Schuchardt [53]). This surgical technique and its modifications were currently used to manage the surgical closure of open bite [54, 55], transverse maxillary deficiency [55, 56, 57], or excess [55, 58]. The last two findings are common in patients with UCLP. After proper soft tissue management of severe and longstanding oronasal fistulas [12], this approach favors the 3D maxillary architecture prior to secondary orthognathic surgery, reduces prosthodontic needs and creates a more cost-effective alternative than using either conventional LeFort I advancement plus extensive prosthodontic replacement or interdental osteogenic distraction [58].
A combination of surgical fistula closure followed by a combination of Le Fort I advancements in two segments [59] plus immediate or delayed alveolar bone graft, depending on the need and extension of additional distraction osteogenesis/orthognathic surgery has been used regularly at the Clínica Noel Foundation since 2015, modified from Stal et al. [12] (Figure 9). This maxillary procedure could be performed alone or in combination with BSSO during the same surgical procedure. This modified approach produce good bone blood flow [60], and stability [61], with fair gingival architecture due to pre-existing periodontal conditions that can be worsened in some cases by local tension on the flaps during gingival closure [59] (Figure 5). Good-to-fair results regarding non-tension flap closure, bone-to-bone contact, and secondary bone healing have been obtained, depending on the degree of cleft maxillary hypoplasia present. For these patients, these successive surgical steps (oronasal fistula treatment followed by segmental maxillary approximation) could be realized previous or simultaneously to the placement of a narrow tertiary alveolar bone grafting and the realization of additional surgical mandibular procedures during orthognathic surgery.
Application of Segmental Maxillary Advancement to reduce the Alveolar Cleft prior to Final Bone Grafting. Pre-surgical records. a. Close-up of alveolar cleft, b. Occlusal view, c. Periapical radiograph, d. CT close-up occlusal view: 10 mm gap between internal radicular surfaces, e. CT occlusal maxillary view; Post-surgical records. f. Close-up of alveolar cleft, g. Occlusal view, h. Periapical radiograph, i. CT close-up occlusal view: 5 mm gap between internal radicular surfaces, j. CT occlusal maxillary view. The left segmental advancement reduced in half the distance to be covered by a tertiary bone grafting and increased the chances of closure success.
Distraction osteogenesis is a treatment technique that deals with the genesis and growth of new bone in a specific body area, through the application of gradual tensile stress [62, 63, 64, 65, 66]. Distraction Osteogenesis can be applied to the surgical correction of hypoplasias of the craniofacial skeleton to replace extensive bone and soft tissue deficiencies without requiring the use of bone grafts [67]. This technique additionally provides the benefit of expanding the overlying soft tissues, which are frequently deficient in these patients.
After the introduction of gradual elastic maxillary distraction to advance a segmental Le Fort I osteotomy (an incipient form of Distraction Osteogenesis -DO) by Wassmund [68], maxillary DO using facemask and elastic traction was successfully reintroduced by Molina and coworkers 60 years later [69], after several animal studies corroborated its feasibility [70, 71]. After the arrival of the Rigid External Distraction (RED) technique for its use for upper and mid-face hypoplasia in 1997 [72], Polley and Figueroa applied their maxillary DO technique in cleft patients [73, 74] and Figueroa and co-workers reported their immediate and long results in this population [75, 76]. In patients with either UCLP or BCLP that present severe maxillary hypoplasia (GOSLON 5 and 5+), worsened by previous pharyngeal repairs that apply additional tension to an already deficient cleft maxillary development, this alternative surgical technique allows the progressive forward displacement of the maxillary complex, while exerts moderate but increasing tension in the pharyngeal musculature that favors their rearrangement in the final maxillary position [73, 74, 75, 76].
Patients prior to the surgical procedure received preferably a customized rigid labial-palatal arch with external vertical hooks adapted partially from a face-bow, or with detachable external hooks located distal to the lateral incisors (Figure 10). These orthodontic options facilitate further distraction modifications and appliance removal in dental settings. After this, the patient was submitted to a high LeFort I osteotomy (in segments according to cleft type), avoiding tooth germs and external halo frame positioning. After 5–7 days latency period, active distraction is performed at 1 mm/day at 0.5 mm each 12 hours, until an additional 20% of the planned DO is achieved. Orthodontic follow-up is highly recommended to control the amount of distraction remaining, to change the direction of distraction when needed, and to give additional instructions to the patient and relatives on how to adjust the distraction if any AP and transverse maxilla-mandible asymmetry is developing. The average amount of maxillary RED distraction in such cases was 9.6 mm [76]. A consolidation period of 3+ months with the distractor in place must be observed to allow maxillary bone to mature from the initially delayed woven bone and guaranteed the obtained results.
Intraoral Tooth-Supported Devices for RED system. a. Customized rigid labial-palatal arch with external vertical hooks adapted partially from a face-bow, b. Customized rigid labial-palatal with detachable external hooks located distal to the lateral incisors.
Despite the appearance of other maxillary DO external and internal devices, the RED system allows the application of important pulling forces to advance the receding maxillary complex without risking external frame integrity, permits to correct direction of distraction due to their flexibility in distractors’ positioning on vertical and horizontals bars [77], and manage a wider range of maxillary distraction than internal DO devices. A maxillary cleft case treated with this approach appears below (Figure 11).
Patient with Maxillary Cleft undergoing Maxillary RED. a. Before maxillary DO; b. During Distraction Osteogenesis; c. After DO. Notice the improvement on maxillary projection at the infraorbital level.
Adult patients affected by CL ± CP require reduced treatment times while obtaining optimal craniofacial results. After obtaining a one-piece maxilla (Except in patients GOSLON2, some GOSLON2+, and GOSLON3 that finished ortho-surgical treatment at the end of SABG) and at the end of maxillary DO in patients GOSLON5 and 5+, the Craniofacial Ortho-Surgical team has to properly plan and execute orthognathic surgery that address three-dimensionally all problems related with the surgical correction of an asymmetric patient. Could a combination of treatments according to the state of the art be used to reduce treatment times in an interdisciplinary scheme? There are several contemporary alternatives from the orthodontic-surgical treatment stand point that can be used in this scenario: First, the re-appearance of self-ligating systems (with passive -regular [e.g. Damon™ System, Ormco Corp., Orange, CA] or CAD-CAM individualized brackets [e.g. Insignia™ System, Ormco Corp., Orange, CA]-, or interactive brackets [e.g. CCO™ System, Dentsply Sirona Orthodontics, York, PA]), and second, the spreading use of Surgical Treatment Acceleration (Surgery-First and Surgery-Early surgical approaches).
Both alternatives are not new. Passive Self-Ligation is an old therapeutic alternative available for clinical use in the 70’s [78] and 80’s [79]. The concept was commercially reintroduced in the late 90’s by the Ormco™ Task Force, to give origin to the Damon™ System [80, 81]. One of its objectives is supposedly to reduce clinical activity time and treatment time -reduction in wire changes and face-to-face clinical activity-, and increase clinical efficiency by simplifying orthodontic mechanics and materials. The passive effect of friction reduction by bracket design is especially noticed during tooth leveling and alignment in severe dental crowding, dentoalveolar expansion, and in less extent during major tooth movements [80, 81]. The second objective is to take advantage of the active use of orthodontic archwires with variable activation temperature. This is the most important change from early self-ligating appliances. Buehler and coworkers were the first to explain the physical properties of the Variable Transformation Temperature concept [82], while Tien and collaborators in 1982 described its application in orthodontics [83]. Later, Burstone and others published on the alloy characteristics and clinical behavior in depth [84, 85, 86, 87]. Thermo-activated wires allow clinicians (1) to use a differential alloy sequence, that permit early cross-sectional form changes and wire gauge increments to fill entirely the bracket’s slot at early treatment stages with early effect of torque, and (2) to take advantage of wider archforms than in current straight-wire systems. This characteristic is potentiated with self-ligation to produce a “free” vestibular tooth movement by using wider arch shapes on unconventional alloys in a shorter period of time [88, 89, 90]. Total appointment time and treatment length could be shorter due to the fulfillment of both objectives in most cases. However, no differences in the positions of incisors and the transverse dimension changes of the maxillary arch were found when self-ligated appliances and conventional-ligated appliances plus Quad-Helix were compared [91]. There is insufficient evidence to justify or contraindicate its use in surgical orthodontics in patients with CL ± CP [30].
Surgical Treatment Acceleration is not a new technique either. During the 1960–1970’s, the early orthognathic surgery approaches were performed without orthodontist intervention (Surgery first -independent-), and subsequent orthodontic treatment was poorly encouraged by maxillofacial surgeons afterwards [92, 93, 94]. Several problems, including the lack of interrelation of orthodontic and surgical treatments, and difficulties for space generation needed for correct orthodontic decompensation, aroused from these early attempts. After the realization that occlusal relationships were a key component of orthognathic surgery results, the orthodontist gained a role in both craniofacial and maxillofacial teams with the objective to eliminate dental compensations before surgery and facilitate posterior orthodontic treatment [95]. The basic sequence of procedures is still applied today. However, creating a maxilla-mandibular decompensation, alignment, and correct maxilla-mandibular anterior and transversal relationships is a long process, even today. A different approach was proposed by Epker and Fish in [96]. They affirmed that it was best to perform surgical procedures as soon as possible to obtain immediate post-surgical benefits for orthodontic treatment (accelerated orthodontic movement after surgery following surgical correction), surgical improvement (early recovery of facial and dental function), and functional aspects (improvements on speech and deglution). Sugawara and Tohoku University/University of Connecticut group in 2009 proposed their Surgery First Approach (SFA) -also called Surgery-First/Early Orthognathic Approach (SFEA) [97]- combined with Skeletal Anchorage System (SAS) for the treatment of a skeletal Class III patient, obtaining excellent results based on the premises mentioned previously [98]. In 2019, the same group published its extensive follow-up on Temporo-Mandibular Symptoms and Function in Class III malocclusion using SFEA compared with Orthodontics-First Approach (OFA) patients, without significant differences between groups [99]. CES University, in conjunction with the mentioned consortium [100], and with the Universidad del Valle [101] have applied SFEA schemes in Latin-American patients. SFEA rely on performing orthognathic surgery at the beginning of treatment with minimal preoperative orthodontics [102]. This treatment protocol allows the reduction in time of pre-surgical treatment (obtaining one-year reduction in average), with the patient’s benefit of an early improvement in facial esthetics. It can be applied not only in patients with UCLP and Class III malocclusion (GOSLON3+ onwards), but also in patients with UCLP and Class II malocclusion (GOSLON 1 and 1+), with or without skeletal vertical discrepancies.
Chang Gung Memorial Hospital group general guidelines for such approach states the following advantages of the procedure as follows [103, 104]: (1) Shorter pre-surgical orthodontic treatment time; (2) Reduction in the difficulty of post-surgical treatment through Regional Acceleratory Phenomena (RAP) [104]; (3) Possibility of planning and computer-guided execution (CAD-CAM); (4) Same effect on ATM as with traditional scheme, in addition to the surgical and functional advantages already mentioned. The post-operative rapid (accelerated) orthodontic tooth movement after SFEA in both dental arches is significant and is due to the increase in odontoclasts activity and dentoalveolar metabolic changes [105]. However, some disadvantages of SFEA include: (1) The need of careful orthodontic-surgical planning; (2) The preparation of the orthodontic-surgical team; (3) The appearance of possible post-surgical orthodontic problems; (4) A poor post-operative stability [97], in opposition to favorable long-term stability reported previously [96].
Mahmood and coworkers suggested that implementing a modified Surgery-Early protocol to speed-up final orthodontic-surgical treatment for CL ± CP patients would be useful [102]. However, Seo and coworkers found smaller incisor overjet, maxillary intercanine and intermolar ratios, and ratio of intercanine and intermolar distance in a group of surgical patients with UCLP and Class III malocclusion prepared to be treated with SFEA, than in a non-cleft group with a dentofacial deformity. The same group had also smaller anterior teeth contact number and larger incisor overjet than patients with UCLP and Class III malocclusion treated with a conventional protocol [106]. These difficulties have to be weighed when planning surgical procedures under this approach.
As a summary of the SFEA application, this modified version of the steps for performing orthognathic surgery under this approach are [103]: (1) Short period (≤6 months) of AP and vertical maxilla-mandibular decompensating orthodontics before the operation; (2) Reduction of possible dental collisions and minimal decompensation of mandibular teeth, through segmental maxillary surgery planning, surgically assisted rapid palatal expansion, or post-operative orthodontic tooth movement; (3) First / Early Modified Surgery 3D Model; (4) First/Early surgery based on specific therapeutic planning. Total treatment time is shortened in around 1 year, depending of the complexity of the remaining orthodontic treatment [103]. Treatment results of a patient with UCLP GOSLON4+ are shown in Figure 12.
Patient with UCLP undergoing maxillo-mandibular asymmetry correction through Surgery-First/Early Approach and Passive Self-ligation. a. and b. Before treatment; c. and d. Previous to Surgery-Early Approach. Noticed the dental changes obtained in the maxillary dentition by the use of passive self-ligation appliances; e. and f. After Surgery-Early Approach; d. After the end of treatment. Treatment time before treatment-surgery: 6 months, 25 days; Total Treatment time: 20 months, 25 days.
The anterior information can be summarized to perform apparently different treatment choices in a rational order that will allow clinicians to identify the increasing difficulty of surgical orthodontic approaches used in the resolution of alveolar cleft with or without distraction osteogenesis and final orthognathic surgery (Figures 13 and 14).
Mixed dentition treatment algorithm for patients with UCLP. The final prognosis and outcome using this approach depends on severity of the cleft, the degree of mandibular deviation, and the surgical ability of the craniofacial team to obtain the desired goals.
Alternative treatment algorithm for adult patients with UCLP. A more expedite protocol following the same parameters (severity of the cleft, degree of mandibular deviation, and surgical ability of the craniofacial team) is performed in all patients with UCLP who have non-repaired clefts and require a definitive solution to their craniofacial difference.
Orthodontic treatment for patients with unilateral cleft lip and palate varies in the level of difficulty due to the increased involvement of orthodontic and surgical procedures involved, the correct timing of applying the complete treatment strategy, and the need of additional procedures to treat several dental anomalies present in teeth adjacent to the cleft, such as dental form and size anomalies, localized enamel hypoplasia, abnormal teeth number, and dental formation disturbances.
Our modified GOSLON+ yardstick allow us to categorize patients with UCLP in several discrete groups according to maxillary growth. Our treatment algorithms allow us to deliver appropriate treatment of the adolescent and young adult patients requiring effective orthodontic intervention for all surgical needs in our patient-based hospital settings in Colombia.
To CES University, who allowed me to experience all procedures described in this chapter.
To Universidad de Antioquia for their support.
To Clínica Noel Foundation to allow me access to all records used in this chapter.
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settings. She is now a lecturer at the University of Witwatersrand, South Africa, and a principal researcher at the Health Economics and Epidemiology Research Office (HE2RO), South Africa. Dr. Moolla holds a Ph.D. in Psychology with her research being focused on mental health and resilience. In her professional work capacity, her research has further expanded into the fields of early childhood development, mental health, the HIV and TB care cascades, as well as COVID. She is also a UNESCO-trained International Bioethics Facilitator.",institutionString:"University of the Witwatersrand",institution:{name:"University of the Witwatersrand",country:{name:"South Africa"}}},{id:"419588",title:"Ph.D.",name:"Sergio",middleName:"Alexandre",surname:"Gehrke",slug:"sergio-gehrke",fullName:"Sergio Gehrke",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000038WgMKQA0/Profile_Picture_2022-06-02T11:44:20.jpg",biography:"Dr. Sergio Alexandre Gehrke is a doctorate holder in two fields. The first is a Ph.D. in Cellular and Molecular Biology from the Pontificia Catholic University, Porto Alegre, Brazil, in 2010 and the other is an International Ph.D. in Bioengineering from the Universidad Miguel Hernandez, Elche/Alicante, Spain, obtained in 2020. In 2018, he completed a postdoctoral fellowship in Materials Engineering in the NUCLEMAT of the Pontificia Catholic University, Porto Alegre, Brazil. He is currently the Director of the Postgraduate Program in Implantology of the Bioface/UCAM/PgO (Montevideo, Uruguay), Director of the Cathedra of Biotechnology of the Catholic University of Murcia (Murcia, Spain), an Extraordinary Full Professor of the Catholic University of Murcia (Murcia, Spain) as well as the Director of the private center of research Biotecnos – Technology and Science (Montevideo, Uruguay). Applied biomaterials, cellular and molecular biology, and dental implants are among his research interests. He has published several original papers in renowned journals. In addition, he is also a Collaborating Professor in several Postgraduate programs at different universities all over the world.",institutionString:null,institution:{name:"Universidad Católica San Antonio de Murcia",country:{name:"Spain"}}},{id:"342152",title:"Dr.",name:"Santo",middleName:null,surname:"Grace Umesh",slug:"santo-grace-umesh",fullName:"Santo Grace Umesh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/342152/images/16311_n.jpg",biography:null,institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}},{id:"333647",title:"Dr.",name:"Shreya",middleName:null,surname:"Kishore",slug:"shreya-kishore",fullName:"Shreya Kishore",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333647/images/14701_n.jpg",biography:"Dr. Shreya Kishore completed her Bachelor in Dental Surgery in Chettinad Dental College and Research Institute, Chennai, and her Master of Dental Surgery (Orthodontics) in Saveetha Dental College, Chennai. She is also Invisalign certified. She’s working as a Senior Lecturer in the Department of Orthodontics, SRM Dental College since November 2019. She is actively involved in teaching orthodontics to the undergraduates and the postgraduates. Her clinical research topics include new orthodontic brackets, fixed appliances and TADs. She’s published 4 articles in well renowned indexed journals and has a published patency of her own. Her private practice is currently limited to orthodontics and works as a consultant in various clinics.",institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}},{id:"323731",title:"Prof.",name:"Deepak M.",middleName:"Macchindra",surname:"Vikhe",slug:"deepak-m.-vikhe",fullName:"Deepak M. Vikhe",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/323731/images/13613_n.jpg",biography:"Dr Deepak M.Vikhe .\n\n\t\n\tDr Deepak M.Vikhe , completed his Masters & PhD in Prosthodontics from Rural Dental College, Loni securing third rank in the Pravara Institute of Medical Sciences Deemed University. He was awarded Dr.G.C.DAS Memorial Award for Research on Implants at 39th IPS conference Dubai (U A E).He has two patents under his name. He has received Dr.Saraswati medal award for best research for implant study in 2017.He has received Fully funded scholarship to Spain ,university of Santiago de Compostela. He has completed fellowship in Implantlogy from Noble Biocare. \nHe has attended various conferences and CDE programmes and has national publications to his credit. His field of interest is in Implant supported prosthesis. Presently he is working as a associate professor in the Dept of Prosthodontics, Rural Dental College, Loni and maintains a successful private practice specialising in Implantology at Rahata.\n\nEmail: drdeepak_mvikhe@yahoo.com..................",institutionString:null,institution:{name:"Pravara Institute of Medical Sciences",country:{name:"India"}}},{id:"204110",title:"Dr.",name:"Ahmed A.",middleName:null,surname:"Madfa",slug:"ahmed-a.-madfa",fullName:"Ahmed A. Madfa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204110/images/system/204110.jpg",biography:"Dr. Madfa is currently Associate Professor of Endodontics at Thamar University and a visiting lecturer at Sana'a University and University of Sciences and Technology. He has more than 6 years of experience in teaching. His research interests include root canal morphology, functionally graded concept, dental biomaterials, epidemiology and dental education, biomimetic restoration, finite element analysis and endodontic regeneration. Dr. Madfa has numerous international publications, full articles, two patents, a book and a book chapter. Furthermore, he won 14 international scientific awards. Furthermore, he is involved in many academic activities ranging from editorial board member, reviewer for many international journals and postgraduate students' supervisor. Besides, I deliver many courses and training workshops at various scientific events. Dr. Madfa also regularly attends international conferences and holds administrative positions (Deputy Dean of the Faculty for Students’ & Academic Affairs and Deputy Head of Research Unit).",institutionString:"Thamar University",institution:null},{id:"210472",title:"Dr.",name:"Nermin",middleName:"Mohammed Ahmed",surname:"Yussif",slug:"nermin-yussif",fullName:"Nermin Yussif",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/210472/images/system/210472.jpg",biography:"Dr. Nermin Mohammed Ahmed Yussif is working at the Faculty of dentistry, University for October university for modern sciences and arts (MSA). Her areas of expertise include: periodontology, dental laserology, oral implantology, periodontal plastic surgeries, oral mesotherapy, nutrition, dental pharmacology. She is an editor and reviewer in numerous international journals.",institutionString:"MSA University",institution:null},{id:"204606",title:"Dr.",name:"Serdar",middleName:null,surname:"Gözler",slug:"serdar-gozler",fullName:"Serdar Gözler",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204606/images/system/204606.jpeg",biography:"Dr. Serdar Gözler has completed his undergraduate studies at the Marmara University Faculty of Dentistry in 1978, followed by an assistantship in the Prosthesis Department of Dicle University Faculty of Dentistry. Starting his PhD work on non-resilient overdentures with Assoc. Prof. Hüsnü Yavuzyılmaz, he continued his studies with Prof. Dr. Gürbüz Öztürk of Istanbul University Faculty of Dentistry Department of Prosthodontics, this time on Gnatology. He attended training programs on occlusion, neurology, neurophysiology, EMG, radiology and biostatistics. In 1982, he presented his PhD thesis \\Gerber and Lauritzen Occlusion Analysis Techniques: Diagnosis Values,\\ at Istanbul University School of Dentistry, Department of Prosthodontics. As he was also working with Prof. Senih Çalıkkocaoğlu on The Physiology of Chewing at the same time, Gözler has written a chapter in Çalıkkocaoğlu\\'s book \\Complete Prostheses\\ entitled \\The Place of Neuromuscular Mechanism in Prosthetic Dentistry.\\ The book was published five times since by the Istanbul University Publications. Having presented in various conferences about occlusion analysis until 1998, Dr. Gözler has also decided to use the T-Scan II occlusion analysis method. Having been personally trained by Dr. Robert Kerstein on this method, Dr. Gözler has been lecturing on the T-Scan Occlusion Analysis Method in conferences both in Turkey and abroad. Dr. Gözler has various articles and presentations on Digital Occlusion Analysis methods. He is now Head of the TMD Clinic at Prosthodontic Department of Faculty of Dentistry , Istanbul Aydın University , Turkey.",institutionString:"Istanbul Aydin University",institution:{name:"Istanbul Aydın University",country:{name:"Turkey"}}},{id:"240870",title:"Ph.D.",name:"Alaa Eddin Omar",middleName:null,surname:"Al Ostwani",slug:"alaa-eddin-omar-al-ostwani",fullName:"Alaa Eddin Omar Al Ostwani",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/240870/images/system/240870.jpeg",biography:"Dr. Al Ostwani Alaa Eddin Omar received his Master in dentistry from Damascus University in 2010, and his Ph.D. in Pediatric Dentistry from Damascus University in 2014. Dr. Al Ostwani is an assistant professor and faculty member at IUST University since 2014. \nDuring his academic experience, he has received several awards including the scientific research award from the Union of Arab Universities, the Syrian gold medal and the international gold medal for invention and creativity. Dr. Al Ostwani is a Member of the International Association of Dental Traumatology and the Syrian Society for Research and Preventive Dentistry since 2017. He is also a Member of the Reviewer Board of International Journal of Dental Medicine (IJDM), and the Indian Journal of Conservative and Endodontics since 2016.",institutionString:"International University for Science and Technology.",institution:{name:"Islamic University of Science and Technology",country:{name:"India"}}},{id:"42847",title:"Dr.",name:"Belma",middleName:null,surname:"Işik Aslan",slug:"belma-isik-aslan",fullName:"Belma Işik Aslan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/42847/images/system/42847.jpg",biography:"Dr. Belma IşIk Aslan was born in 1976 in Ankara-TURKEY. After graduating from TED Ankara College in 1994, she attended to Gazi University, Faculty of Dentistry in Ankara. She completed her PhD in orthodontic education at Gazi University between 1999-2005. Dr. Işık Aslan stayed at the Providence Hospital Craniofacial Institude and Reconstructive Surgery in Michigan, USA for three months as an observer. She worked as a specialist doctor at Gazi University, Dentistry Faculty, Department of Orthodontics between 2005-2014. She was appointed as associate professor in January, 2014 and as professor in 2021. Dr. Işık Aslan still works as an instructor at the same faculty. She has published a total of 35 articles, 10 book chapters, 39 conference proceedings both internationally and nationally. Also she was the academic editor of the international book 'Current Advances in Orthodontics'. She is a member of the Turkish Orthodontic Society and Turkish Cleft Lip and Palate Society. She is married and has 2 children. Her knowledge of English is at an advanced level.",institutionString:"Gazi University Dentistry Faculty Department of Orthodontics",institution:null},{id:"178412",title:"Associate Prof.",name:"Guhan",middleName:null,surname:"Dergin",slug:"guhan-dergin",fullName:"Guhan Dergin",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178412/images/6954_n.jpg",biography:"Assoc. Prof. Dr. Gühan Dergin was born in 1973 in Izmit. He graduated from Marmara University Faculty of Dentistry in 1999. He completed his specialty of OMFS surgery in Marmara University Faculty of Dentistry and obtained his PhD degree in 2006. In 2005, he was invited as a visiting doctor in the Oral and Maxillofacial Surgery Department of the University of North Carolina, USA, where he went on a scholarship. Dr. Dergin still continues his academic career as an associate professor in Marmara University Faculty of Dentistry. He has many articles in international and national scientific journals and chapters in books.",institutionString:null,institution:{name:"Marmara University",country:{name:"Turkey"}}},{id:"178414",title:"Prof.",name:"Yusuf",middleName:null,surname:"Emes",slug:"yusuf-emes",fullName:"Yusuf Emes",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178414/images/6953_n.jpg",biography:"Born in Istanbul in 1974, Dr. Emes graduated from Istanbul University Faculty of Dentistry in 1997 and completed his PhD degree in Istanbul University faculty of Dentistry Department of Oral and Maxillofacial Surgery in 2005. He has papers published in international and national scientific journals, including research articles on implantology, oroantral fistulas, odontogenic cysts, and temporomandibular disorders. Dr. Emes is currently working as a full-time academic staff in Istanbul University faculty of Dentistry Department of Oral and Maxillofacial Surgery.",institutionString:null,institution:{name:"Istanbul University",country:{name:"Turkey"}}},{id:"192229",title:"Ph.D.",name:"Ana Luiza",middleName:null,surname:"De Carvalho Felippini",slug:"ana-luiza-de-carvalho-felippini",fullName:"Ana Luiza De Carvalho Felippini",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192229/images/system/192229.jpg",biography:null,institutionString:"University of São Paulo",institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"256851",title:"Prof.",name:"Ayşe",middleName:null,surname:"Gülşen",slug:"ayse-gulsen",fullName:"Ayşe Gülşen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/256851/images/9696_n.jpg",biography:"Dr. Ayşe Gülşen graduated in 1990 from Faculty of Dentistry, University of Ankara and did a postgraduate program at University of Gazi. \nShe worked as an observer and research assistant in Craniofacial Surgery Departments in New York, Providence Hospital in Michigan and Chang Gung Memorial Hospital in Taiwan. \nShe works as Craniofacial Orthodontist in Department of Aesthetic, Plastic and Reconstructive Surgery, Faculty of Medicine, University of Gazi, Ankara Turkey since 2004.",institutionString:"Univeristy of Gazi",institution:null},{id:"255366",title:"Prof.",name:"Tosun",middleName:null,surname:"Tosun",slug:"tosun-tosun",fullName:"Tosun Tosun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255366/images/7347_n.jpg",biography:"Graduated at the Faculty of Dentistry, University of Istanbul, Turkey in 1989;\nVisitor Assistant at the University of Padua, Italy and Branemark Osseointegration Center of Treviso, Italy between 1993-94;\nPhD thesis on oral implantology in University of Istanbul and was awarded the academic title “Dr.med.dent.”, 1997;\nHe was awarded the academic title “Doç.Dr.” (Associated Professor) in 2003;\nProficiency in Botulinum Toxin Applications, Reading-UK in 2009;\nMastership, RWTH Certificate in Laser Therapy in Dentistry, AALZ-Aachen University, Germany 2009-11;\nMaster of Science (MSc) in Laser Dentistry, University of Genoa, Italy 2013-14.\n\nDr.Tosun worked as Research Assistant in the Department of Oral Implantology, Faculty of Dentistry, University of Istanbul between 1990-2002. \nHe worked part-time as Consultant surgeon in Harvard Medical International Hospitals and John Hopkins Medicine, Istanbul between years 2007-09.\u2028He was contract Professor in the Department of Surgical and Diagnostic Sciences (DI.S.C.), Medical School, University of Genova, Italy between years 2011-16. \nSince 2015 he is visiting Professor at Medical School, University of Plovdiv, Bulgaria. \nCurrently he is Associated Prof.Dr. at the Dental School, Oral Surgery Dept., Istanbul Aydin University and since 2003 he works in his own private clinic in Istanbul, Turkey.\u2028\nDr.Tosun is reviewer in journal ‘Laser in Medical Sciences’, reviewer in journal ‘Folia Medica\\', a Fellow of the International Team for Implantology, Clinical Lecturer of DGZI German Association of Oral Implantology, Expert Lecturer of Laser&Health Academy, Country Representative of World Federation for Laser Dentistry, member of European Federation of Periodontology, member of Academy of Laser Dentistry. Dr.Tosun presents papers in international and national congresses and has scientific publications in international and national journals. He speaks english, spanish, italian and french.",institutionString:null,institution:{name:"Istanbul Aydın University",country:{name:"Turkey"}}},{id:"171887",title:"Prof.",name:"Zühre",middleName:null,surname:"Akarslan",slug:"zuhre-akarslan",fullName:"Zühre Akarslan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/171887/images/system/171887.jpg",biography:"Zühre Akarslan was born in 1977 in Cyprus. She graduated from Gazi University Faculty of Dentistry, Ankara, Turkey in 2000. \r\nLater she received her Ph.D. degree from the Oral Diagnosis and Radiology Department; which was recently renamed as Oral and Dentomaxillofacial Radiology, from the same university. \r\nShe is working as a full-time Associate Professor and is a lecturer and an academic researcher. \r\nHer expertise areas are dental caries, cancer, dental fear and anxiety, gag reflex in dentistry, oral medicine, and dentomaxillofacial radiology.",institutionString:"Gazi University",institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"256417",title:"Associate Prof.",name:"Sanaz",middleName:null,surname:"Sadry",slug:"sanaz-sadry",fullName:"Sanaz Sadry",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/256417/images/8106_n.jpg",biography:null,institutionString:null,institution:null},{id:"272237",title:"Dr.",name:"Pinar",middleName:"Kiymet",surname:"Karataban",slug:"pinar-karataban",fullName:"Pinar Karataban",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/272237/images/8911_n.png",biography:"Assist.Prof.Dr.Pınar Kıymet Karataban, DDS PhD \n\nDr.Pınar Kıymet Karataban was born in Istanbul in 1975. After her graduation from Marmara University Faculty of Dentistry in 1998 she started her PhD in Paediatric Dentistry focused on children with special needs; mainly children with Cerebral Palsy. She finished her pHD thesis entitled \\'Investigation of occlusion via cast analysis and evaluation of dental caries prevalance, periodontal status and muscle dysfunctions in children with cerebral palsy” in 2008. She got her Assist. Proffessor degree in Istanbul Aydın University Paediatric Dentistry Department in 2015-2018. ın 2019 she started her new career in Bahcesehir University, Istanbul as Head of Department of Pediatric Dentistry. In 2020 she was accepted to BAU International University, Batumi as Professor of Pediatric Dentistry. She’s a lecturer in the same university meanwhile working part-time in private practice in Ege Dental Studio (https://www.egedisklinigi.com/) a multidisciplinary dental clinic in Istanbul. Her main interests are paleodontology, ancient and contemporary dentistry, oral microbiology, cerebral palsy and special care dentistry. She has national and international publications, scientific reports and is a member of IAPO (International Association for Paleodontology), IADH (International Association of Disability and Oral Health) and EAPD (European Association of Pediatric Dentistry).",institutionString:null,institution:null},{id:"202198",title:"Dr.",name:"Buket",middleName:null,surname:"Aybar",slug:"buket-aybar",fullName:"Buket Aybar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/202198/images/6955_n.jpg",biography:"Buket Aybar, DDS, PhD, was born in 1971. She graduated from Istanbul University, Faculty of Dentistry, in 1992 and completed her PhD degree on Oral and Maxillofacial Surgery in Istanbul University in 1997.\nDr. Aybar is currently a full-time professor in Istanbul University, Faculty of Dentistry Department of Oral and Maxillofacial Surgery. She has teaching responsibilities in graduate and postgraduate programs. Her clinical practice includes mainly dentoalveolar surgery.\nHer topics of interest are biomaterials science and cell culture studies. She has many articles in international and national scientific journals and chapters in books; she also has participated in several scientific projects supported by Istanbul University Research fund.",institutionString:null,institution:null},{id:"260116",title:"Dr.",name:"Mehmet",middleName:null,surname:"Yaltirik",slug:"mehmet-yaltirik",fullName:"Mehmet Yaltirik",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/260116/images/7413_n.jpg",biography:"Birth Date 25.09.1965\r\nBirth Place Adana- Turkey\r\nSex Male\r\nMarrial Status Bachelor\r\nDriving License Acquired\r\nMother Tongue Turkish\r\n\r\nAddress:\r\nWork:University of Istanbul,Faculty of Dentistry, Department of Oral Surgery and Oral Medicine 34093 Capa,Istanbul- TURKIYE",institutionString:null,institution:null},{id:"172009",title:"Dr.",name:"Fatma Deniz",middleName:null,surname:"Uzuner",slug:"fatma-deniz-uzuner",fullName:"Fatma Deniz Uzuner",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/172009/images/7122_n.jpg",biography:"Dr. Deniz Uzuner was born in 1969 in Kocaeli-TURKEY. After graduating from TED Ankara College in 1986, she attended the Hacettepe University, Faculty of Dentistry in Ankara. \nIn 1993 she attended the Gazi University, Faculty of Dentistry, Department of Orthodontics for her PhD education. After finishing the PhD education, she worked as orthodontist in Ankara Dental Hospital under the Turkish Government, Ministry of Health and in a special Orthodontic Clinic till 2011. Between 2011 and 2016, Dr. Deniz Uzuner worked as a specialist in the Department of Orthodontics, Faculty of Dentistry, Gazi University in Ankara/Turkey. In 2016, she was appointed associate professor. Dr. Deniz Uzuner has authored 23 Journal Papers, 3 Book Chapters and has had 39 oral/poster presentations. She is a member of the Turkish Orthodontic Society. 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Since 1995, he has been working on: i) the determination in biological fluids (serum, urine, bronchoalveolar lavage, sputum) of proteolytic activities involved in the degradation processes of connective tissue matrix, and ii) on the identification of biological markers of lung diseases. In this context, he has developed and validated new methodologies (e.g., Capillary Electrophoresis coupled to Laser-Induced Fluorescence, CE-LIF) whose application enabled him to determine both the amounts of biochemical markers (Desmosines) in urine/serum of patients affected by Chronic Obstructive Pulmonary Disease (COPD) and the activity of proteolytic enzymes (Human Neutrophil Elastase, Cathepsin G, Pseudomonas aeruginosa elastase) in sputa of these patients. More recently, Prof. Iadarola was involved in developing techniques such as two-dimensional electrophoresis coupled to liquid chromatography/mass spectrometry (2DE-LC/MS) for the proteomic analysis of biological fluids aimed at the identification of potential biomarkers of different lung diseases. He is the author of about 150 publications (According to Scopus: H-Index: 23; Total citations: 1568- According to WOS: H-Index: 20; Total Citations: 1296) of peer-reviewed international journals. He is a Consultant Reviewer for several journals, including the Journal of Chromatography A, Journal of Chromatography B, Plos ONE, Proteomes, International Journal of Molecular Science, Biotech, Electrophoresis, and others. He is also Associate Editor of Biotech.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorTwo:{id:"201414",title:"Dr.",name:"Simona",middleName:null,surname:"Viglio",slug:"simona-viglio",fullName:"Simona Viglio",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKDHQA4/Profile_Picture_1630402531487",biography:"Simona Viglio is an Associate Professor of Biochemistry at the Department of Molecular Medicine at the University of Pavia. She has been working since 1995 on the determination of proteolytic enzymes involved in the degradation process of connective tissue matrix and on the identification of biological markers of lung diseases. She gained considerable experience in developing and validating new methodologies whose applications allowed her to determine both the amount of biomarkers (Desmosine and Isodesmosine) in the urine of patients affected by COPD, and the activity of proteolytic enzymes (HNE, Cathepsin G, Pseudomonas aeruginosa elastase) in the sputa of these patients. Simona Viglio was also involved in research dealing with the supplementation of amino acids in patients with brain injury and chronic heart failure. She is presently engaged in the development of 2-DE and LC-MS techniques for the study of proteomics in biological fluids. The aim of this research is the identification of potential biomarkers of lung diseases. She is an author of about 90 publications (According to Scopus: H-Index: 23; According to WOS: H-Index: 20) on peer-reviewed journals, a member of the “Società Italiana di Biochimica e Biologia Molecolare,“ and a Consultant Reviewer for International Journal of Molecular Science, Journal of Chromatography A, COPD, Plos ONE and Nutritional Neuroscience.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorThree:null,series:{id:"11",title:"Biochemistry"}}},seriesLanding:{item:{id:"11",title:"Biochemistry",doi:"10.5772/intechopen.72877",issn:"2632-0983",scope:"Biochemistry, the study of chemical transformations occurring within living organisms, impacts all areas of life sciences, from molecular crystallography and genetics to ecology, medicine, and population biology. Biochemistry examines macromolecules - proteins, nucleic acids, carbohydrates, and lipids – and their building blocks, structures, functions, and interactions. Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. This Biochemistry Series will address the current research on biomolecules and the emerging trends with great promise.",coverUrl:"https://cdn.intechopen.com/series/covers/11.jpg",latestPublicationDate:"June 29th, 2022",hasOnlineFirst:!0,numberOfOpenTopics:4,numberOfPublishedChapters:318,numberOfPublishedBooks:32,editor:{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",fullName:"Miroslav Blumenberg",profilePictureURL:"https://mts.intechopen.com/storage/users/31610/images/system/31610.jpg",biography:"Miroslav Blumenberg, Ph.D., was born in Subotica and received his BSc in Belgrade, Yugoslavia. He completed his Ph.D. at MIT in Organic Chemistry; he followed up his Ph.D. with two postdoctoral study periods at Stanford University. Since 1983, he has been a faculty member of the RO Perelman Department of Dermatology, NYU School of Medicine, where he is codirector of a training grant in cutaneous biology. Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}},subseries:[{id:"14",title:"Cell and Molecular Biology",keywords:"Omics (Transcriptomics; Proteomics; Metabolomics), Molecular Biology, Cell Biology, Signal Transduction and Regulation, Cell Growth and Differentiation, Apoptosis, Necroptosis, Ferroptosis, Autophagy, Cell Cycle, Macromolecules and Complexes, Gene Expression",scope:"The Cell and Molecular Biology topic within the IntechOpen Biochemistry Series aims to rapidly publish contributions on all aspects of cell and molecular biology, including aspects related to biochemical and genetic research (not only in humans but all living beings). We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics include, but are not limited to: Advanced techniques of cellular and molecular biology (Molecular methodologies, imaging techniques, and bioinformatics); Biological activities at the molecular level; Biological processes of cell functions, cell division, senescence, maintenance, and cell death; Biomolecules interactions; Cancer; Cell biology; Chemical biology; Computational biology; Cytochemistry; Developmental biology; Disease mechanisms and therapeutics; DNA, and RNA metabolism; Gene functions, genetics, and genomics; Genetics; Immunology; Medical microbiology; Molecular biology; Molecular genetics; Molecular processes of cell and organelle dynamics; Neuroscience; Protein biosynthesis, degradation, and functions; Regulation of molecular interactions in a cell; Signalling networks and system biology; Structural biology; Virology and microbiology.",annualVolume:11410,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/14.jpg",editor:{id:"165627",title:"Dr.",name:"Rosa María",middleName:null,surname:"Martínez-Espinosa",fullName:"Rosa María Martínez-Espinosa",profilePictureURL:"https://mts.intechopen.com/storage/users/165627/images/system/165627.jpeg",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"79367",title:"Dr.",name:"Ana Isabel",middleName:null,surname:"Flores",fullName:"Ana Isabel Flores",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRpIOQA0/Profile_Picture_1632418099564",institutionString:null,institution:{name:"Hospital Universitario 12 De Octubre",institutionURL:null,country:{name:"Spain"}}},{id:"328234",title:"Ph.D.",name:"Christian",middleName:null,surname:"Palavecino",fullName:"Christian Palavecino",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000030DhEhQAK/Profile_Picture_1628835318625",institutionString:null,institution:{name:"Central University of Chile",institutionURL:null,country:{name:"Chile"}}},{id:"186585",title:"Dr.",name:"Francisco Javier",middleName:null,surname:"Martin-Romero",fullName:"Francisco Javier Martin-Romero",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSB3HQAW/Profile_Picture_1631258137641",institutionString:null,institution:{name:"University of Extremadura",institutionURL:null,country:{name:"Spain"}}}]},{id:"15",title:"Chemical Biology",keywords:"Phenolic Compounds, Essential Oils, Modification of Biomolecules, Glycobiology, Combinatorial Chemistry, Therapeutic peptides, Enzyme Inhibitors",scope:"Chemical biology spans the fields of chemistry and biology involving the application of biological and chemical molecules and techniques. In recent years, the application of chemistry to biological molecules has gained significant interest in medicinal and pharmacological studies. This topic will be devoted to understanding the interplay between biomolecules and chemical compounds, their structure and function, and their potential applications in related fields. Being a part of the biochemistry discipline, the ideas and concepts that have emerged from Chemical Biology have affected other related areas. This topic will closely deal with all emerging trends in this discipline.",annualVolume:11411,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",institutionString:null,institution:{name:"Anadolu University",institutionURL:null,country:{name:"Turkey"}}},editorTwo:{id:"13652",title:"Prof.",name:"Deniz",middleName:null,surname:"Ekinci",fullName:"Deniz Ekinci",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYLT1QAO/Profile_Picture_1634557223079",institutionString:null,institution:{name:"Ondokuz Mayıs University",institutionURL:null,country:{name:"Turkey"}}},editorThree:null,editorialBoard:[{id:"219081",title:"Dr.",name:"Abdulsamed",middleName:null,surname:"Kükürt",fullName:"Abdulsamed Kükürt",profilePictureURL:"https://mts.intechopen.com/storage/users/219081/images/system/219081.png",institutionString:null,institution:{name:"Kafkas University",institutionURL:null,country:{name:"Turkey"}}},{id:"241413",title:"Dr.",name:"Azhar",middleName:null,surname:"Rasul",fullName:"Azhar Rasul",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRT1oQAG/Profile_Picture_1635251978933",institutionString:null,institution:{name:"Government College University, Faisalabad",institutionURL:null,country:{name:"Pakistan"}}},{id:"178316",title:"Ph.D.",name:"Sergey",middleName:null,surname:"Sedykh",fullName:"Sergey Sedykh",profilePictureURL:"https://mts.intechopen.com/storage/users/178316/images/system/178316.jfif",institutionString:null,institution:{name:"Novosibirsk State University",institutionURL:null,country:{name:"Russia"}}}]},{id:"17",title:"Metabolism",keywords:"Biomolecules Metabolism, Energy Metabolism, Metabolic Pathways, Key Metabolic Enzymes, Metabolic Adaptation",scope:"Metabolism is frequently defined in biochemistry textbooks as the overall process that allows living systems to acquire and use the free energy they need for their vital functions or the chemical processes that occur within a living organism to maintain life. Behind these definitions are hidden all the aspects of normal and pathological functioning of all processes that the topic ‘Metabolism’ will cover within the Biochemistry Series. Thus all studies on metabolism will be considered for publication.",annualVolume:11413,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",editor:{id:"138626",title:"Dr.",name:"Yannis",middleName:null,surname:"Karamanos",fullName:"Yannis Karamanos",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6Jv2QAE/Profile_Picture_1629356660984",institutionString:null,institution:{name:"Artois University",institutionURL:null,country:{name:"France"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"243049",title:"Dr.",name:"Anca",middleName:null,surname:"Pantea Stoian",fullName:"Anca Pantea Stoian",profilePictureURL:"https://mts.intechopen.com/storage/users/243049/images/system/243049.jpg",institutionString:null,institution:{name:"Carol Davila University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"203824",title:"Dr.",name:"Attilio",middleName:null,surname:"Rigotti",fullName:"Attilio Rigotti",profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institutionString:null,institution:{name:"Pontifical Catholic University of Chile",institutionURL:null,country:{name:"Chile"}}},{id:"300470",title:"Dr.",name:"Yanfei (Jacob)",middleName:null,surname:"Qi",fullName:"Yanfei (Jacob) Qi",profilePictureURL:"https://mts.intechopen.com/storage/users/300470/images/system/300470.jpg",institutionString:null,institution:{name:"Centenary Institute of Cancer Medicine and Cell Biology",institutionURL:null,country:{name:"Australia"}}}]},{id:"18",title:"Proteomics",keywords:"Mono- and Two-Dimensional Gel Electrophoresis (1-and 2-DE), Liquid Chromatography (LC), Mass Spectrometry/Tandem Mass Spectrometry (MS; MS/MS), Proteins",scope:"With the recognition that the human genome cannot provide answers to the etiology of a disorder, changes in the proteins expressed by a genome became a focus in research. Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. The Proteomics topic aims to attract contributions on all aspects of MS-based proteomics that, by pushing the boundaries of MS capabilities, may address biological problems that have not been resolved yet.",annualVolume:11414,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",editor:{id:"200689",title:"Prof.",name:"Paolo",middleName:null,surname:"Iadarola",fullName:"Paolo Iadarola",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSCl8QAG/Profile_Picture_1623568118342",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorTwo:{id:"201414",title:"Dr.",name:"Simona",middleName:null,surname:"Viglio",fullName:"Simona Viglio",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKDHQA4/Profile_Picture_1630402531487",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorThree:null,editorialBoard:[{id:"72288",title:"Dr.",name:"Arli Aditya",middleName:null,surname:"Parikesit",fullName:"Arli Aditya Parikesit",profilePictureURL:"https://mts.intechopen.com/storage/users/72288/images/system/72288.jpg",institutionString:null,institution:{name:"Indonesia International Institute for Life Sciences",institutionURL:null,country:{name:"Indonesia"}}},{id:"40928",title:"Dr.",name:"Cesar",middleName:null,surname:"Lopez-Camarillo",fullName:"Cesar Lopez-Camarillo",profilePictureURL:"https://mts.intechopen.com/storage/users/40928/images/3884_n.png",institutionString:null,institution:{name:"Universidad Autónoma de la Ciudad de México",institutionURL:null,country:{name:"Mexico"}}},{id:"81926",title:"Dr.",name:"Shymaa",middleName:null,surname:"Enany",fullName:"Shymaa Enany",profilePictureURL:"https://mts.intechopen.com/storage/users/81926/images/system/81926.png",institutionString:"Suez Canal University",institution:{name:"Suez Canal University",institutionURL:null,country:{name:"Egypt"}}}]}]}},libraryRecommendation:{success:null,errors:{},institutions:[]},route:{name:"profile.detail",path:"/profiles/106366",hash:"",query:{},params:{id:"106366"},fullPath:"/profiles/106366",meta:{},from:{name:null,path:"/",hash:"",query:{},params:{},fullPath:"/",meta:{}}}},function(){var e;(e=document.currentScript||document.scripts[document.scripts.length-1]).parentNode.removeChild(e)}()