Summary of contemporary randomized trials on LD‐EBRT of painful heel spurs: tested schedules, results, and conclusions.
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Barely three months into the new year and we are happy to announce a monumental milestone reached - 150 million downloads.
\n\nThis achievement solidifies IntechOpen’s place as a pioneer in Open Access publishing and the home to some of the most relevant scientific research available through Open Access.
\n\nWe are so proud to have worked with so many bright minds throughout the years who have helped us spread knowledge through the power of Open Access and we look forward to continuing to support some of the greatest thinkers of our day.
\n\nThank you for making IntechOpen your place of learning, sharing, and discovery, and here’s to 150 million more!
\n\n\n\n\n'}],latestNews:[{slug:"intechopen-supports-asapbio-s-new-initiative-publish-your-reviews-20220729",title:"IntechOpen Supports ASAPbio’s New Initiative Publish Your Reviews"},{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"}]},book:{item:{type:"book",id:"9060",leadTitle:null,fullTitle:"The Current Perspectives on Coronary Artery Bypass Grafting",title:"The Current Perspectives on Coronary Artery Bypass Grafting",subtitle:null,reviewType:"peer-reviewed",abstract:"This book, The Current Perspectives on Coronary Artery Bypass Grafting, is an excellent update for health care professionals taking care of patients suffering from severe coronary artery disease. The nine chapters in this book were written by experts in their fields. The first section describes the hemodynamic mechanism and medical management of coronary artery disease. The second section describes the most recent evidence and controversial topics in the field of coronary artery bypass grafting. I believe this book will serve the interests of readers.",isbn:"978-1-78985-966-9",printIsbn:"978-1-78985-965-2",pdfIsbn:"978-1-83962-857-3",doi:"10.5772/intechopen.83055",price:119,priceEur:129,priceUsd:155,slug:"the-current-perspectives-on-coronary-artery-bypass-grafting",numberOfPages:176,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"cedc3547eae8f66f9440cc35216d7963",bookSignature:"Takashi Murashita",publishedDate:"July 29th 2020",coverURL:"https://cdn.intechopen.com/books/images_new/9060.jpg",numberOfDownloads:7031,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:4,numberOfDimensionsCitationsByBook:0,hasAltmetrics:1,numberOfTotalCitations:4,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"March 18th 2019",dateEndSecondStepPublish:"September 4th 2019",dateEndThirdStepPublish:"November 3rd 2019",dateEndFourthStepPublish:"January 22nd 2020",dateEndFifthStepPublish:"March 22nd 2020",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"192448",title:"Dr.",name:"Takashi",middleName:null,surname:"Murashita",slug:"takashi-murashita",fullName:"Takashi Murashita",profilePictureURL:"https://mts.intechopen.com/storage/users/192448/images/system/192448.jpg",biography:"Takashi Murashita, MD, is an assistant professor in the Department of Surgery, University of Missouri, USA. Dr. Murashita received his MD from Kyoto University Medical School, Japan. His main interest is cardiac surgery, and he is a member of the Society of Thoracic Surgery, Eastern Cardiothoracic Surgical Society, and Asian Society for Cardiovascular and Thoracic Surgery. He has published fifty-three papers in peer-reviewed journals and ten book chapters. He has been an editorial board member and ad hoc manuscript reviewer for several medical journals.",institutionString:"University of Missouri",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"11",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"University of Missouri",institutionURL:null,country:{name:"United States of America"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"984",title:"Cardiac Surgery",slug:"cardiac-surgery"}],chapters:[{id:"69357",title:"Current Status, Perspectives, and Future Directions of Multivessel Disease and Left Main Coronary Disease: Its Treatment by PCI or Surgery",doi:"10.5772/intechopen.89419",slug:"current-status-perspectives-and-future-directions-of-multivessel-disease-and-left-main-coronary-dise",totalDownloads:626,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"MVD has evolved from an era where it was mandatory to treat all lesions, even very thin vessels. With the advent of more realistic anatomical scores such as the ERACI score and the gradient measurements with the fractional flow of reserve (FFR) and instantaneous wave-free ratio (iwFR), a more conservative era has begun, which benefits the patient in the long-term follow-up. The treatment of the LMCA remains a challenging lesion because of the amount of irrigation. It can be divided the treatment of the LMCA with a low or high ERACI score, in the first group is where the PCI has gained in confidence and dedication in addition to knowledge and bifurcation techniques. The second group with high score can only be performed in centers with high PCI experience, since their alternative will always be surgical as the first choice. The revascularization in MVD with STEMI, the priority is the culprit vessel and then evaluate the underlying lesions, an invasive or with a functional test in the short term. The patient with DM is a singular patient, and its treatment should always be evaluated by a multidisciplinary team. We believe that patients with low ERACI score have the possibility of being treated with PCI, but patients with high score are surgical.",signatures:"Juan Mieres and Alfredo E. Rodríguez",downloadPdfUrl:"/chapter/pdf-download/69357",previewPdfUrl:"/chapter/pdf-preview/69357",authors:[{id:"164686",title:"Dr.",name:"Juan",surname:"Mieres",slug:"juan-mieres",fullName:"Juan Mieres"}],corrections:null},{id:"69546",title:"Evaluation of the Effect of Increased Arterial Stiffness on Ejection Performance and Pulmonary Arterial Pressure in Primary Mitral Regurgitation and Prediction of Ejection Fraction after Surgery: Analysis Using Wave Intensity",doi:"10.5772/intechopen.89458",slug:"evaluation-of-the-effect-of-increased-arterial-stiffness-on-ejection-performance-and-pulmonary-arter",totalDownloads:588,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Mitral regurgitation (MR) is a common valvular disorder that has important health consequences. Surgical therapy is associated with reduced long-term mortality in elder patients. Several guidelines exist regarding when and in whom to perform mitral valve surgery, but they are controversial. It is essential to obtain preoperative indices that are promising for predicting postoperative left ventricular function and right ventricular pressure correctly. In aged MR patients, various hemodynamic conditions are presumed to be the causes of higher rate of mortality. In addition, aging causes increase in arterial stiffness. Therefore, it is also important to consider the effects of increased arterial stiffness on hemodynamics in MR. This review was written on the basis of our studies of wave intensity and will focus on the effects of increased arterial stiffness with a specific emphasis on wave intensity, which provides quantitative information about hemodynamic interaction between the ventricle and the arterial system.",signatures:"Kiyomi Niki and Motoaki Sugawara",downloadPdfUrl:"/chapter/pdf-download/69546",previewPdfUrl:"/chapter/pdf-preview/69546",authors:[{id:"289111",title:"Prof.",name:"Motoaki",surname:"Sugawara",slug:"motoaki-sugawara",fullName:"Motoaki Sugawara"},{id:"300005",title:"Prof.",name:"Kiyomi",surname:"Niki",slug:"kiyomi-niki",fullName:"Kiyomi Niki"}],corrections:null},{id:"70422",title:"Antiplatelet Therapy after Coronary Artery Bypass Graft Surgery, Inconsistency of Clinical Practice and Clinical Significance of Proven Resistance to Antiplatelet Agents",doi:"10.5772/intechopen.90446",slug:"antiplatelet-therapy-after-coronary-artery-bypass-graft-surgery-inconsistency-of-clinical-practice-a",totalDownloads:690,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Antiplatelet therapy is a very important part of medical therapy for patients after acute coronary syndrome (ACS) as well as in a stable coronary artery disease (CAD). The use of antiplatelet therapy after coronary artery bypass graft surgery (CABG) still is a controversial theme in daily clinical practice. While guidelines referring to dual antiplatelet therapy (DAPT) after ACS with proceeding percutaneous coronary intervention (PCI) are uniform, there are doubts regarding DAPT after CABG, especially in setting of chronic coronary syndrome (CCS). Recommendations are mostly based on expert opinion and not on multiple randomized controlled trials (RCT) or meta-analyses. Resistance to aspirin (acetylsalicylic acid, ASA) or other antiplatelet drugs is known after CABG, and further RCTs are needed to assess the effect on clinical outcome as well as the role of DAPT after CABG.",signatures:"Ivana Sopek Merkas, Nenad Lakusic, Krunoslav Fuckar, Dusko Cerovec and Kristina Maric Besic",downloadPdfUrl:"/chapter/pdf-download/70422",previewPdfUrl:"/chapter/pdf-preview/70422",authors:[{id:"310936",title:"Dr.",name:"Ivana",surname:"Sopek Merkaš",slug:"ivana-sopek-merkas",fullName:"Ivana Sopek Merkaš"},{id:"311065",title:"Prof.",name:"Nenad",surname:"Lakušić",slug:"nenad-lakusic",fullName:"Nenad Lakušić"},{id:"314597",title:"Dr.",name:"Krunoslav",surname:"Fučkar",slug:"krunoslav-fuckar",fullName:"Krunoslav Fučkar"},{id:"314598",title:"Dr.",name:"Duško",surname:"Cerovec",slug:"dusko-cerovec",fullName:"Duško Cerovec"},{id:"314599",title:"Dr.",name:"Kristina",surname:"Marić Bešić",slug:"kristina-maric-besic",fullName:"Kristina Marić Bešić"}],corrections:null},{id:"68877",title:"Role of Medical Therapy in Chronic Mitral Regurgitation",doi:"10.5772/intechopen.89027",slug:"role-of-medical-therapy-in-chronic-mitral-regurgitation",totalDownloads:761,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Mitral regurgitation is one of the most commonly encountered valvular heart diseases in both the developing and the developed world. From various studies, it is known that chronic mitral regurgitation is associated with progressive left ventricular dysfunction, and eventually death if left untreated. This disease has a long silent period before symptoms manifest. During this latent period, left ventricular function progressively deteriorates and results in poor outcomes for patients even if surgery is performed. A few studies have evaluated the role of medical therapy in patients with chronic mitral regurgitation. This chapter will provide an overview of the use of medical therapy in chronic mitral regurgitation.",signatures:"Ruchika Meel",downloadPdfUrl:"/chapter/pdf-download/68877",previewPdfUrl:"/chapter/pdf-preview/68877",authors:[{id:"273730",title:"Dr.",name:"Ruchika",surname:"Meel",slug:"ruchika-meel",fullName:"Ruchika Meel"}],corrections:null},{id:"70032",title:"Coronary Artery Bypass Grafting: Surgical Anastomosis: Tips and Tricks",doi:"10.5772/intechopen.88932",slug:"coronary-artery-bypass-grafting-surgical-anastomosis-tips-and-tricks",totalDownloads:1426,totalCrossrefCites:0,totalDimensionsCites:3,hasAltmetrics:0,abstract:"The definite feature of coronary artery disease is the focal narrowing in the vascular endothelium, and this leads to the decrease in the flow of blood to the myocardium. Atherosclerotic plaque is the main lesion. These patients can present with chest pain (angina or myocardial infarction) and need further workup noninvasively and invasively for the management. The main reasons for myocardial revascularization can be: (1) relief from symptoms of myocardial ischemia; (2) reduce the risks of future mortality; (3) to treat or prevent morbidities such as myocardial infarction, arrhythmias, or heart failure. Coronary artery bypass grafting (CABG) is the surgical technique of cardiac revascularization. In 1910, Dr. Alexis Carrel described a series of canine experiments in which he devised means to treat CAD by creating a “complementary circulation” for the diseased native coronary arteries. No clinical translation occurred at the time, but he was awarded the Nobel Prize in Medicine. Experimental refinements of coronary arterial revascularization, including the use of internal thoracic artery (ITA) grafts, were later reported by Murray and colleagues, Demikhov, and Goetz and colleagues in the 1950s and early 1960s. Dr. Rene Favaloro performed his first coronary bypass operation in May 1967 with an interposed saphenous vein graft (SVG) and shortly thereafter used aortocoronary bypasses sutured proximally to the ascending aorta. The stenosed segment is bypassed using an arterial or venous graft. Left internal thoracic artery is the most commonly used artery, and long saphenous vein is the most commonly used vein for the coronary artery grafting to reestablish the blood flow to the compromised myocardium. This can be performed with or without the help of cardiopulmonary bypass machine and also with or without arresting the heart. These techniques are called as on-pump beating or on-pump arrested and off-pump beating coronary artery bypass grafting surgery. Distal and proximal anastomoses are usually performed in an end-to-side manner, but in the case of doing sequential grafting, side-to-side anastomosis is also performed proximal to the end-to-side anastomosis. In this chapter we are going to discuss the coronary artery bypass grafting tips and tricks in details.",signatures:"Mohd. Shahbaaz Khan",downloadPdfUrl:"/chapter/pdf-download/70032",previewPdfUrl:"/chapter/pdf-preview/70032",authors:[{id:"278633",title:"Dr.",name:"Mohd. Shahbaaz",surname:"Khan",slug:"mohd.-shahbaaz-khan",fullName:"Mohd. Shahbaaz Khan"}],corrections:null},{id:"69049",title:"Early and Late Survival and Associated Factors in Patients Undergoing Coronary Artery Bypass Grafting",doi:"10.5772/intechopen.89141",slug:"early-and-late-survival-and-associated-factors-in-patients-undergoing-coronary-artery-bypass-graftin",totalDownloads:598,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Several studies have aimed to compare the early and late survival rates and the related factors in patients who undergo coronary artery bypass grafting (CABG). Among such factors are age, gender, arrhythmia, stroke, serum procalcitonin level, number and type of grafts, diabetes mellitus, chronic kidney disease, chronic obstructive pulmonary disease (COPD), addiction, ejection fraction, transfusion of blood products, and the kind of technique (off-pump versus on-pump). Controversies surround early and late survival and some of the associated factors in patients undergoing CABG. Therefore, it appears vital to compare the early and late survival chances and the related factors after CABG.",signatures:"Ahmad Amouzeshi and Zahra Amouzeshi",downloadPdfUrl:"/chapter/pdf-download/69049",previewPdfUrl:"/chapter/pdf-preview/69049",authors:[{id:"300192",title:"Associate Prof.",name:"Ahmad",surname:"Amouzeshi",slug:"ahmad-amouzeshi",fullName:"Ahmad Amouzeshi"},{id:"300193",title:"MSc.",name:"Zahra",surname:"Amouzeshi",slug:"zahra-amouzeshi",fullName:"Zahra Amouzeshi"}],corrections:null},{id:"69992",title:"Should We Do Bilateral Internal Mammary Artery Grafting in Diabetic Patients?",doi:"10.5772/intechopen.89652",slug:"should-we-do-bilateral-internal-mammary-artery-grafting-in-diabetic-patients-",totalDownloads:412,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:1,abstract:"Nowadays, potential advantages of BIMA grafting are recognized overall in terms of long-term survival1 and by not increasing operative morbidity. One of the major restrictions for extending the use of BIMA grafting is the current impossibility of generalizing the procedure to higher risk patients. These results tend to confirm recent results that promote the use of BIMA grafting in every kind of patients and consequently to confirm the generalization of the procedure, without being afraid of sternal complications. The absence of deep sternal wound infection in our study shows that there is no contraindication of BITA grafting among diabetic patients.",signatures:"Hassane Abdallah, Ahmed Ibrahim and Khalid Al Khamees",downloadPdfUrl:"/chapter/pdf-download/69992",previewPdfUrl:"/chapter/pdf-preview/69992",authors:[{id:"43710",title:"Dr.",name:"Hassane",surname:"Abdallah",slug:"hassane-abdallah",fullName:"Hassane Abdallah"}],corrections:null},{id:"69694",title:"Right Internal Thoracic Artery with an Anteroaortic Course",doi:"10.5772/intechopen.89807",slug:"right-internal-thoracic-artery-with-an-anteroaortic-course",totalDownloads:867,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Coronary artery bypass graft surgery remains the procedure of choice to revascularize patients with complex multivessel coronary artery disease. The left internal thoracic artery and saphenous vein are the most commonly utilized conduits in coronary artery bypass graft surgery. The left internal thoracic artery is widely accepted as the conduit of choice for coronary artery bypass grafting. Accumulated evidence in recent years has demonstrated the superiority of bilateral internal thoracic artery grafting over single internal thoracic artery grafting in terms of event-free survival, freedom from reintervention and survival. The survival benefit seen with bilateral internal thoracic artery grafting has been associated particularly with grafting the myocardium supplied by the left coronary artery system. Many surgical strategies have been tested in order to achieve left-sided myocardial revascularization with bilateral internal thoracic artery grafting. These include directing the right internal thoracic artery through the transverse sinus in a retroaortic course, free graft connected proximally either to the left internal thoracic artery (composite grafting) or to the ascending aorta. Another technical option is in situ right internal thoracic artery to the left anterior descending and left internal thoracic artery to circumflex marginal branches; in this chapter we will comment on this technique.",signatures:"Maurilio O. Deininger, Orlando G. Oliveira, Daniel M.S. Magalhães and Eugenia Di G. Deininger",downloadPdfUrl:"/chapter/pdf-download/69694",previewPdfUrl:"/chapter/pdf-preview/69694",authors:[{id:"301247",title:"Ph.D.",name:"Maurilio",surname:"Deininger",slug:"maurilio-deininger",fullName:"Maurilio Deininger"},{id:"301251",title:"Dr.",name:"Orlando",surname:"Oliveira",slug:"orlando-oliveira",fullName:"Orlando Oliveira"},{id:"301252",title:"Dr.",name:"Daniel",surname:"Magalhaes",slug:"daniel-magalhaes",fullName:"Daniel Magalhaes"},{id:"309995",title:"Dr.",name:"Eugenia",surname:"Deininger",slug:"eugenia-deininger",fullName:"Eugenia Deininger"}],corrections:null},{id:"72679",title:"Tips and Tricks in Microvascular Anastomoses",doi:"10.5772/intechopen.92903",slug:"tips-and-tricks-in-microvascular-anastomoses",totalDownloads:1067,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:1,abstract:"Microvascular anastomosis is a highly skilled surgical technique that requires the assistance of optical magnification via an operating microscope or loupes to be fully visualised and thus accomplished reasonably well. It demands the full attention of the surgeon throughout the procedure. Even the smallest of inadvertencies may result in disastrous results. Practice has no shortcut and the more experienced a skilled surgeon is, the better his results. The chapter begins with a detailed account of preparedness in the operating room, for preparation is the path to success. There are however tips to reduce the incline of the learning curve and points to remember when things are not quite going right. This chapter attempts to deal with those moments.",signatures:"Sharifah Ahmad Roohi",downloadPdfUrl:"/chapter/pdf-download/72679",previewPdfUrl:"/chapter/pdf-preview/72679",authors:[{id:"214913",title:"Prof.",name:"S.A.",surname:"Roohi",slug:"s.a.-roohi",fullName:"S.A. 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The most common cause of this symptom is the so‐called “plantar fasciitis” [2]. This term is widely used, although “plantar fasciopathy” or “plantar fasciosis” would be a better description to point out the degenerative nature of the disease. However, as more than 1100 citations in Pubmed quote “plantar fasciitis” (in comparison with only 50), we will use the traditional term in the following.
Plantar fasciitis has been associated with obesity, with acute or chronic work overload, or with work on hard surfaces [2, 3]. It seems that physiological degeneration of the fascia at the calcaneal insertion exacerbates due to repetitive microtraumas caused by vertical compression [4]. This causes inflammatory tissue reactions. As a result, the fascia is thickened with an associated fluid collection to 4.0 mm and more in ultrasonography [5]. Furthermore, this inflammation may trigger bone formation, the so‐called “plantar heel spur.” This process has been studied intensively by Kumai and Benjamin [6]. They proposed three stages of spur growth: “(a) an initial formation of cartilage cell clusters and fissures at the plantar fascia enthesis; (b) thickening of the subchondral bone plate at the enthesis as small spurs form; and (c) development of vertically oriented trabeculae buttressing the proximal end of larger spurs” [6]. The first description of this spur formation and correlation with the clinical symptoms was carried out by Plettner in 1900 [7]. However, not every heel spur is associated with heel pain, as these spurs are found in 11–16% of the normal asymptomatic population [4]. On the other hand, some patients with painful plantar fasciitis do not have a radiographic confirmation of a spur formation.
A similar mechanism (although caused by longitudinal traction and not by vertical compression) of bone formation has been described at the insertion of the Achilles tendon [8].
According to the American clinical practice guidelines from 2010, diagnosis is established by the typical anamnesis and the characteristic localizations of tenderness. Still, weight‐bearing radiographs are also recommended [9].
Single doses of external beam radiotherapy (EBRT) in the range of 0.3–1 Gy are called “low dose EBRT” (LD‐EBRT). These single fractions are applied two or three times a week until a total dose of about 3–6 Gy is reached. Such radiotherapeutic concepts are used for diverse nonmalignant conditions, e.g., osteoarthrosis, tendinopathy, epicondylitis, or bursitis. A comprehensive review of the historical developments in LD‐EBRT for benign diseases is given by Trott [10].
In contrast, EBRT in oncology is characterized by much higher single and total doses. “Normofractionation” describes single doses of 1.8–2 Gy, applied about five times a week. To treat breast cancer, the total doses of about 62 Gy are necessary, in prostate cancer even more than 72 Gy. From a radiobiological point of view, these high cumulative doses are used to induce DNA double strand breaks. Due to errors in a repair mechanism (nonhomologous end joining), dicentric chromosomes can occur. These can result in unfinished mitoses, the so‐called “mitotic catastrophe,” the main mechanism to reduce clonogenic survival in tumor cells [11]. High doses of EBRT induce local inflammation and tissue reactions.
The much lower doses of LD‐EBRT act via different mechanisms. In the last two decades, several anti‐inflammatory effects have been discovered, contrary to the effects of the above‐mentioned high EBRT doses.
Furthermore, doses between 0.1 and 0.5 Gy reduced the adhesion of PBMC significantly to endothelial cells (ECs)
A third mechanism was the suppression of nitric oxide (NO) production in activated macrophages by LD‐EBRT between 0.3 and 1.25 Gy [18]. As the expression of inducible nitric oxide synthases (iNOS) proteins was not altered, the LD‐EBRT seemed to act at the translational or posttranslational level. Furthermore, a dose of 0.5 Gy significantly reduced oxidative burst and superoxide production of stimulated macrophages [19]. A diminished release of reactive oxygen species (ROS) can also contribute to the anti‐inflammatory effects of LD‐EBRT.
Taken together, all of these pathways and mechanisms showed a similar dose dependence with a maximum effect between 0.3 and 0.7 Gy regarding a discontinuous dose‐effect relation [20].
There are several
Since 1937 [21] for decades, large retrospective studies on the efficacy of LD‐EBRT in calcaneodynia have been published (overview in 22). In 1970, one negative randomized trial was reported and heavily criticized but had not been repeated [23]. Starting in the 1980s, patients were systematically clinically examined and interrogated in a structured manner to try to control for diverse risk factors and to compare the efficacy of different fractionation schemes and total doses [24].
It took until the past decade to perform and report prospectively randomized trials to proof the efficacy of LD‐EBRT and to identify the optimal dose fractionation schedule. In the following, we report the design and the results of these trials. Table 1 gives a short overview of the studied dose concepts and the results. Due to methodological reasons, we will describe the studies not following their publications dates, but according to a systematic order.
Since the publication of the first randomized trial on LD-EBRT in 1970, the efficacy of LD‐EBRT was questioned [23]. Goldie et al. randomized 399 patients, however, only nine patients suffered from calcaneodynia. This is why these results cannot be extrapolated to LD‐EBRT of a painful heel spur. Furthermore, endpoints were not clearly defined, and therapy was started in an acute stage of the disease [25].
The landmark study to prove the efficacy of LD‐EBRT was performed by the German cooperative group on the radiotherapy for benign diseases (GCGBD) under the responsibility of Niewald et al. [26]. A very low dose EBRT (6 × 0.1 Gy applied twice a week up to a total dose of 0.6 Gy) was randomized to a standard dose LD‐EBRT (6 × 1 Gy twice a week up to a total dose of 6 Gy). In the case of an unfavorable response after 3 months, the patient was offered a second treatment series (“reirradiation”) applying a standard dose. The dosage of the experimental arm was chosen to examine if very low doses are effective at all. Second, it acted as a placebo irradiation, as a sham irradiation was regarded unethical. LD‐EBRT was applied using a linear accelerator (4‐ to 6‐MV photons) using lateral parallel opposing fields.
Inclusion criteria were tenderness of the calcaneus with a limitation of the painless walking distance and duration of the symptoms for more than 6 months. Furthermore, a radiological proof of a heel spur was required, and the patients had to be least 40 years of age. Patients with previous traumata to the foot, rheumatic or vascular diseases, lymphatic edema, pregnancy, or breastfeeding were excluded. Concomitant therapy with oral analgesics was not limited. However, local injections with steroids during the study period were not permitted.
Initially, 200 patients were planned [27] to detect a difference of 10% in the quality of life (QOL) sum score (SF‐12) [28] and calcaneodynia sum score (CS) [29] (Table 2) with a power of 80% and an error probability of 5%. Furthermore, the visual analogue scale (VAS) to evaluate pain intensity was used. However, after randomization of 66 patients and interim analysis of 62 patients (4 had to be excluded due to a withdrawal of informed consent or violation of the inclusion criteria), the differences in efficacy between the two treatment arms were so pronounced, that the trial was closed early.
Author | Year | N | Standard arm | Experimental arm | Results | Conclusions |
---|---|---|---|---|---|---|
2012 | 66 | 6 × 1 Gy twice a week | 6 × 0.1 Gy | 3 months: VAS/CS/SF12 sig. better with standard | 1. Dose‐response relationship | |
1 year: less second treatment series with standard | 2. Proof of therapeutic effect of LD‐EBRT | |||||
2007 | 130 | 6 × 1 Gy twice a week | 6 × 0.5 Gy | 6 months: CS no sig. differences | 6 × 0.5 Gy as standard fractionation | |
2014 | 457 | 6 × 1 Gy twice a week | 6 × 0.5 Gy | 6 weeks, 2.5 years: VAS/CS no sig. differences | 6 × 0.5 Gy as standard confirmed | |
2015 | 127 | 6 × 1 Gy twice a week | 12 × 0.5 Gy thrice a week | 3 months: VAS/CS/SF12 no sig. differences | Efficacy not increased with 12 × 0.5 Gy standard still 6 × 0.5 Gy |
Summary of contemporary randomized trials on LD‐EBRT of painful heel spurs: tested schedules, results, and conclusions.
Criteria | Extent of symptoms/alteration | Points |
---|---|---|
S = Pain at | 6 / 4 / 2 / 0 | |
(total: 30%) | N = Pain during D = Pain during R = Pain at I = Pain at none = 6 ; slight = 4 ; moderate = 2 ; severe = 0 points ⇨ | 6 / 4 / 2 / 0 6 / 4 / 2 / 0 6 / 4 / 2 / 0 6 / 4 / 2 / 0 |
per single criterion | ||
(total: 15%) | None Orthopedic shoe, insoles, heel cushion One cane or crutch Two canes or crutches ⇨ | 15 10 5 0 |
(total: 20%) | No limitation, maximum professional strain possible Slight limitation, normal professional work possible Moderate limitation, reduced professional activity Severe limitation, daily professional work impossible ⇨ | 20 10 5 0 |
(total: 15%) | No limitation of daily and leisure activities and sports Slightly limitation/reduced leisure activities and sports Moderate limitation/no leisure activities and sports Complete limitation of any daily and leisure activities ⇨ | 15 10 5 0 |
(total: 20%) | No limp, normal walking is possible without a limitation Slightly altered, limp after walking Moderately altered, limp after walking Severely altered, normal walking is impossible ⇨ | 20 10 5 0 |
The mean age of patients was 54 years in the standard dose group and 58 years in the 6 × 0.1 Gy group. Sixty‐one patients had a plantar, one patient a dorsal heel spur. In mean, patients in the standard dose group suffered for 15.3 months before the start of LD‐EBRT, in the 6 × 0.1 Gy group for 18.8 months. Twenty‐one patients had symptoms on both sides. In 28 patients the pain irradiated into the calf, only in 18 patients it was localized to the sole of the foot. Two patients had received surgery for LD‐EBRT.
Three months after therapy VAS values, CS‐ and QOL‐scores were significantly better after the standard dose in comparison with the very low dose treatment arm. The higher pain relief resulted in a better QOL. Twelve months after therapy about 64% of the patients after 6 × 0.1 Gy had to receive a second treatment series due to insufficient treatment results, in comparison with only 17% of the patients in the standard dose treatment group. As the second series was applied with a standard dose (6 × 1 Gy), patients in the 6 × 0.1 Gy group who were reirradiated showed equally favorable results compared with those in the standard‐dose group who did not receive a second course [26]. This is why the second treatment series in this clinical setting acted as a “salvage therapy.” Another interesting finding was that patients with a good response already at 3 months remained stable or even improved at 12 months. Furthermore, this underlines the long‐lasting efficacy of LD‐EBRT.
Acute side effects or long‐term toxicity did not occur.
In conclusion, this randomized trial established a dose‐response‐relationship of the analgesic effect of LD‐EBRT, thus providing a clinical and methodological proof of the efficacy of 6 × 1 Gy LD‐EBRT on the clinical course of painful heel spurs. The early termination of the study was justified due the interim analysis showing significant differences in the clinical outcome between both treatment arms. Still, the trial was not blinded, so both the patients and the staff were aware of the received dose. With modern linear accelerators, a complete blinding of the staff is nearly impossible. The only option would be a shame irradiation with closed collimator jaws, reducing the dose to the unavoidable “leakage” radiation. A much easier and straight forward way was used in the above‐mentioned study by application of a minimal physical dose with 0.1 Gy. Another critical point might be that only half of the patients were examined 12 months after therapy (
Another potential confounder not only in this study but also in all other published prospective and retrospective case series might be that a lot of the patients had received diverse and other conservative therapies before being referred to LD‐EBRT. An interaction between one of these other treatments and LD‐EBRT cannot be ruled out due to methodological reasons. This reflects clinical reality. Still, an interaction between one of these therapies and LD‐EBRT is rather unlikely and counter‐intuitive, as patients were referred to LD‐EBRT after the clinical failure of all the other conservative treatments.
Two randomized studies investigated the efficacy of 0.5 Gy single dose in comparison to 1 Gy.
The first trial was conducted by Heyd et al. [30]. They randomized 130 patients between 6 × 0.5 Gy twice weekly (low dose) and 6 × 1 Gy (standard dose). A linear accelerator was used, applying a single field technique.
Inclusion criteria were clinical signs of a painful heel spur, radiological evidence of spur formation, patient age ≥30 years and a relapse after previous conservative treatments, in patients >45 years LD‐EBRT could be used as the primary treatment. Endpoints of the study were changes in the “original” calcaneodynia score [31], that was documented before LD‐EBRT, at the end of the course, and 6 weeks and 6 months afterward.
One hundred and thirty patients were randomized. Mean age was 58.4 years. A 102 patients suffered from a plantar, one patient from a dorsal, and 27 patients from combined spurs. In mean, patients had been suffering from symptoms for 9.8 months. The symptoms had been present in 58 patients for less than 6 months, in 72 patients for a longer time. In 7 heels LD‐EBRT was the first therapeutic approach.
At the end of LD‐EBRT, 66% in the low dose group vs. 59% in the standard dose experienced an improvement in symptoms, 6 weeks later 80 vs. 85%. At this time point, 1.5% in each group reported an increase in symptoms, 19 vs. 14% no change. No statistically significant differences were noted. In case of insufficient treatment results patients were offered a second EBRT series. Thus 26 vs. 37% were treated a second time. Six weeks after that, 71 vs. 79% of these patients reported a further improvement. Six months after LD‐EBRT 88% of the patients in both groups had an amelioration of their symptoms, the remaining patients reported no change. During the EBRT series a slight increase in pain was reported by 26 vs. 29% of the patients. No other acute or late toxicity occurred.
In conclusion, 6 × 0.5 Gy twice weekly was as effective as 6 × 1 Gy.
These results were confirmed by a second randomized trial [32, 33]. Ott et al. randomized 457 patients between 6 × 0.5 Gy (low dose) and 6 × 1 Gy (standard dose). In contrast to the above‐cited “Heyd‐study” [30] an X‐ray unit (orthovoltage) and not linear accelerators was used. Patients received a single field (6 × 8 cm on the plantar calcaneus) with 150 kV, 15 mA, 1 mm Cu‐filter, with source‐to‐skin distance (SSD) of 40 cm. Six weeks after the LD‐EBRT a second series was offered to patients with an insufficient response. The endpoint was pain reduction. CS score and VAS values were measured before and at the end of LD‐EBRT (early response), 6 weeks (delayed), and 2.5 years (long‐term) afterward.
With a median follow‐up of 32 months the mean VAS values before treatment, for early, delayed, and long‐term response for the 0.5 and 1.0 Gy groups were 65.5 ± 22.1 and 64.0 ± 20.5 (
Taken together, the above‐mentioned studies proofed an equivalent clinical efficacy of 6 × 0.5 Gy in comparison to 6 × 1 Gy, thus defining a new clinical treatment standard with six times 0.5 Gy twice weekly as the minimum effective dose.
Before proofing 0.5 Gy as the new standard single dose, another randomized study tried to increase efficacy in reaching the “old” cumulative dose of 6 Gy with a single dose of 0.5 Gy. Niewald et al. randomized between 6 × 1 Gy twice a week (old “standard dose”) and 12 × 0.5 Gy three times a week (“experimental dose”) [25]. The aim was not just to get comparable results, but to further improve the analgesic effects. Linear accelerators (6 MV photons) applying a lateral opposing field technique were used.
Inclusion and exclusion criteria were quite similar to the ones used in the landmark study [26]: Clinical evidence of a painful heel spur, and duration of the symptoms for more than 6 months; radiological proof of a spur formation; age at least 40 years; Karnofsky‐Index at least 70%. Patients with previous radiotherapy or previous trauma to the foot, rheumatic or vascular diseases, lymphatic edema, pregnancy, breastfeeding, or severe psychiatric disorders were excluded. Concomitant therapy with analgesics was allowed. However, patients receiving surgery or shock wave therapy after randomization were excluded.
Endpoints were the SF‐12 sum score, the CS sum score (Table 2), and VAS. Follow‐up was scheduled every 6 weeks for 1 year.
Two‐hundred and forty patients were calculated to detect a difference of 15% in the VAS and CS score, with a power of 80%, and an error probability of 5%. After randomization of 127 patients and an interim analysis of 107 patients, the study was closed early, as the intended increase in analgesic efficacy by the experimental treatment was very unlikely to be achieved.
The mean age of the patients in the standard group was 56.1 Gy in comparison with 58.1 Gy in the experimental group. The mean duration of symptoms before initiation of LD‐EBRT was 17 vs. 16 months. In 98% of the standard group and 93% of the experimental group a plantar spur was treated, in 2 and 7% a combined (plantar and dorsal) spur.
Results after 3 months have been issued so far [25], longer follow‐up has yet to be published. After 3 months, there were no significant differences neither in the VAS (standard 42.3 vs. experimental 44.4) nor the CS sum score (28 vs. 28.4) nor in the QOL (SF‐12) scores. Although longer follow‐up has to be awaited, a further increase in the analgesic effect by applying 12 × 0.5 Gy three times a week is unlikely. This is why this fractionation schedule is currently not recommended, as it does not follow the “as low as reasonable achievable” principle of radiation protection.
Further reduced single doses in LD‐EBRT (with the exception of 0.1 Gy [26]) have never been tested in a prospectively randomized clinical trial. In radiotherapy of degenerative joint disorders, single doses of about 0.3–0.4 Gy were established by von Pannewitz in the late 1920s and published in 1933 and 1970 [34, 35]. However, two studies on calcaneodynia have raised serious concerns on single doses as low as 0.3 Gy.
Seegenschmiedt et al. analyzed treatment efficacy in 141 patients (170 irradiated heels), who were treated from 1984–1994 with X‐ray units (250 kV/200 kV, 20 mA, 40 cm SSD), applying a single field of 6 × 8 cm [24]. Seventy‐two heels received 12 Gy with 6 × 1 Gy (three times a week) –6 weeks break – 6 × 1 Gy (group A), 50 heels were treated with 10 × 0.3 Gy every day (group B1), and 38 heels 10 × 0.5 Gy every day (group B2). The endpoint was the value of a semiquantitative pain score 3 months and in mean 4 years after LD‐EBRT.
The median age of patients was 55 years in group A and 59 years in group B1/B2. The mean duration of symptoms before LD‐EBRT was 8 months, in one‐third, the symptoms persisted for more than 6 months.
Complete pain remission was achieved in 68–71% of the patients without significant differences between the treatment groups. However, there were differences in the clinical course of patients with partial remission of the symptoms: The best results in these patients were achieved during longer follow‐up in group B1 (10 × 0.5 Gy), followed by group A (6 × 1–6 × 1 Gy), followed by group B2 (10 × 0.3 Gy). The latter group showed a significantly worse amelioration of symptoms than the other groups.
A reduced efficacy was also reported in another retrospective case series, comprising 673 heels treated with a single dose of 0.3 Gy three times weekly up to 1.5 Gy (X‐ray) [36]. In case of insufficient treatment results the patients were offered a second course. After the first treatment, only 13% reported CR, nearly all patients had undergone a second LD‐EBRT.
Taken together, to the best of our current knowledge a single dose of 0.5 Gy is standard of care and should only be modified in controlled clinical trials.
In Table 3 selected contemporary randomized trials and patient series are shown broken down into several factors that might be correlated with treatment efficacy. For a better overview, we did not differentiate between univariate and multivariate analyses. We did not try to collect all ever published data.
Duration of symptoms before start of LD‐EBRT has been shown to be correlated with treatment efficacy in numerous studies.
Muecke et al. analyzed in a retrospective multicenter study 502 patients [22]. Duration of symptoms ≤6 months was associated with 76% treatment success vs. 44% after a history >6 months. Also Seegenschmiedt et al. found in their large collectives a correlation between the duration of heel pain and treatment outcome [24]. A significant influence of duration of symptoms before LD‐EBRT was also reported in 73 heels by Schneider et al. [37]. With a history of 3–6 months, the VAS value was reduced by 85%, 28 months after LD‐EBRT in comparison with a reduction of 58% with a history > 6 months. Similar results were obtained by Hermann et al. in 285 heels comparing <12 month history of pain vs. >12 months [38].
In contrary, another study could not confirm these results [30].
To the best of our knowledge, in no study, an influence of gender on treatment outcome has been confirmed [22, 24, 30, 38, 39]. In contrast to radiotherapy for oncological indications with high doses, efficacy and tolerability of LD‐EBRT seems to be the same concerning gender.
Several studies described a correlation between older age and better treatment results, at least 6 weeks after LD‐EBRT [37]. Age somewhat over 50 years seems to be important: >50 years [40], > 53 [38], or > 58 [22]. For a possible explanation see Section 2.3.7.
However, other studies found no influence of this patient characteristic on treatment outcome [24, 30, 39].
A very precise registration of changes in pain intensity (VAS) was done by Schneider at al. [37]. Sixty‐two patients (73 treated heels) were prospectively scored every week during LD‐EBRT, at the end of therapy, 6 weeks, 28 months, and 40 months later. Additionally, subjective mechanical heel stress during LD‐EBRT was estimated. A linear accelerator (10 MV) was used, applying one single field with a size of 12 × 17 cm. Patients were treated twice a week to a total dose of 5 Gy, with increasing single fraction doses (0.25 – 0.25 – 0.5 – 1 – 1 – 1 – 1 Gy). Mean patient age was 54 years, and all had a radiologically proven plantar spurn, mean symptom duration before LD‐EBRT was 6.5 months. Nearly all patients had received other conservative therapies before LD‐EBRT with insufficient results.
Interestingly, VAS scores decreased continuously during LD‐EBRT: before treatment the mean value was 6.3 ± 1.5, after the first week of LD‐EBRT 6.2 ± 1.8, after the second week 5.5 ± 2 (
In standard schedules with fixed single doses a slight increase in pain during the treatment series was reported by 26% (during 6 × 0.5 Gy) vs. 29% (6 × 1 Gy) of the patients [30]. Unfortunately, a possible correlation of this phenomenon with definite treatment results was not investigated.
Without further quantification, another study (6 × 1 vs. 6 × 0.1 Gy) stated, that this initial increase in symptoms “had no influence on the final pain relief 3 and 12 months after treatment” [26]. Older studies postulated a temporary reduction of the pH value in the irradiated tissues at the beginning of the treatment series, without consequences for the long‐term efficacy of LD‐EBRT [41].
This is contrasted by observations of LD‐EBRT in peritendinitis humeroscapularis [42]. In 73 patients (86 shoulders) initial increase of pain during the treatment course was significantly associated with a good response.
Muecke et al. analyzed in a retrospective multicenter study the influence of different treatment techniques in 502 patients [22]. Treatment failure was defined as pain persistence after LD‐EBRT and recurrence of pain during follow‐up. Treatment with MV (6–10 MV) was a significant prognostic factor for pain relief in multivariate analysis, as MV was associated with an eight‐year event‐free probability of 68 vs. 61% after X‐ray beams (175 kV). There are two possible explanations for this finding: besides the possibility of a random result, the authors postulate a more homogenous dose distribution with MV treatment in comparison with KV [22].
Schneider et al. reported an efficacy of just one‐third after a second LD‐EBRT course (so‐called “re‐irradiation”) in comparison with the effects of the first course [37]. Out of 73 heels treated with 5 Gy LD‐EBRT 18 heels received reirradiation due to insufficient treatment response. However, pain reduction measured by means of changes in VAS shortly after the second course and during long‐term follow‐up was significantly diminished in comparison with the efficacy of the first course (about 30% reduction in pain at the last evaluation vs. 86%).
Similar results were obtained in the large retrospective series (502 patients) by Muecke et al. [22]. Treatment failure was significantly associated with the number of treatment series: eight‐year event‐free probability was about 70% after the first course in comparison with just about 30% after reirradiation.
A systematic study on the efficacy of a reirradiation has been published by Hautmann et al. [43]. Eighty‐three patients (101 heels) with insufficient response to the first course or recurrent pain afterward due to plantar fasciitis (83 heels), or achillodynia (28 heels) received a second LD‐EBRT course in median 10 weeks (range 4 weeks to 63 months) after the first LD‐EBRT. About 75% of the patients were treated with 6 × 1 Gy, the others 6 × 0.5 Gy. The pain was assessed using the numeric rating scale (NRS) before and at the end of LD‐EBRT, 6, and 12 weeks, and 6, 12, and 24 months thereafter.
Before reirradiation NRS values were 6 (interquartile range 5–8), at the end of LD‐EBRT 5 (2–6), 6 weeks later 2 (1–4), at 12 weeks 1 (0–3), at 6 months 0 (0–2), at 12 and 24 months 0 (0–1). Interestingly, not only the patients with recurrent pain after the first course but also patients with insufficient responses to the first course experienced a profound and long‐lasting amelioration of their symptoms after the second course.
This is why a second treatment course should be recommended in case of insufficient efficacy of the first course.
A significant correlation between avoidance of heel stress during LD‐EBRT and efficacy of LD‐EBRT 6 weeks after therapy was reported by Schneider et al. in 73 heels [37]. With a Pearson\'s correlation coefficient of -0.467 (
An intuitive explanation is given by the authors [37]: As patient age was associated with positive treatment results, too, they proposed that older patients are often retired, thus being able to take more care of their heels.
Interestingly, all randomized trials required the radiological proof of a heel spur before including patients into the studies. Furthermore, most of the prospective and retrospective series warranted such an objective sign. However, as a substantial part of the patients suffers from plantar heel pain without having developed a heel spur, LD‐EBRT should be effective in these patients, too.
Hermann et al. analyzed treatment efficacy in 250 patients (285 heels), who received LD‐EBRT predominantly with 6 × 1 Gy [38]. In this series, 33% of the treated heels were without radiological evidence of a spur. In 185 patients a spur was confirmed with a mean length of 6.5 mm (range 0.6–25 mm). Patients without evidence of a plantar heel spur had a significantly higher chance of CR after LD‐EBRT (43 vs. 35%). Furthermore, the length of the spurs correlated directly with treatment outcome. Spurs >6.5 mm had just a 30% chance of experiencing CR in comparison with shorter ones. No statistical differences were found between treatment results of heels without spurs and those with spurs ≤6.5 mm.
Miszczyk et al. reported on 327 patients (623 LD‐EBRT series) mostly treated with X‐ray (180 kV, usually 1mm Cu filters) with single doses of 1.5 Gy (range 1–3 Gy) up to a total dose between 9 and 12 Gy (range 1–45 Gy) [39]. Mean spur size was 9 mm (range 1–30 mm). With a mean follow‐up of 74 months, no correlation between spur size and duration of pain relief was found. Analysis concerning spur length and treatment outcome in itself were unfortunately not reported.
Multivariate logistic regression enables the identification of factors independently predicting treatment outcome. By combining these factors, models can be calculated, that predict treatment outcome with a high probability. An example from the study of Hermann et al. is given in Table 4: in 285 heels treated with 6 × 1 Gy/6 × 0.5 Gy the influences of the patient characteristics age, spur length, and duration of symptoms before LD-EBRT alone and in combination were calculated [38]. The best results were obtained for patients > 53 years, spur length <6 mm, and a duration of symptoms <12 months with a probability for CR of 55% (CI 36–73%) and PR of 38% (CI 22–58%). Without these characteristics, the chance for CR was just 18% (CI 9–33%), for PR 31% (17–48%).
Study (citation) | [30] | [26] | [24] | [37] | [39] | [22] | [38] | [40] | [83] |
---|---|---|---|---|---|---|---|---|---|
Rand | Rand | Prospect | Prospect | Retrospect | Retrospect | Retrospect | Retrospect | Retrospect | |
130 | 66 | 170 | 73 | 623 | 502 | 285 | 161 | 7947 | |
MV | MV | KV | MV | KV | MV, KV | MV | KV | MV, KV | |
calcaneus | calcaneus | calcaneus | entire dorsal and middle foot | insertion of plantar fascia | calcaneus | calcaneus vs. insertion of calcaneus | calcaneus | entire dorsal foot vs. calcaneus vs. insertion of plantar fascia | |
6 × 1 vs. 6 × 0.5 Gy | 6 × 1 Gy vs. 6 × 0.1 Gy | 12, 3, 5 Gy | 5 Gy (increasing single dose) | 1.5 (1–3) up to 9–12 Gy (1–45) | 5–10 × 0.5–1 Gy | 6 × 1 Gy6 × 0.5 Gy | 6 × 1 Gy | 0.3–1.5 Gy; 2–3x weekly 2.5–18.76 Gy | |
History of symptoms | 0 | n.i. | + | + | 0 | + | + | + | + |
Gender | 0 | n.i. | 0 | n.i. | 0 | 0 | 0 | n.i. | n.i. |
Patient\'s age | 0 | n.i. | 0 | + | 0 | + | + | + | n.i. |
Initial worsening of pain during LD‐EBRT | n.i. | n.i. | n.i. | n.i. | n.i. | n.i. | n.i. | n.i. | n.i. |
MV vs. KV | n.i. | n.i. | n.i. | n.i. | n.i. | + | n.i. | n.i. | 0 |
Number of therapy series | n.i. | n.i. | n.i. | + | n.i. | + | n.i. | n.i. | + |
Heel stress during LD‐EBRT | n.i. | 0 | n.i. | + | n.i. | n.i. | n.i. | n.i. | n.i. |
Factors associated with treatment efficacy in contemporary studies.
Patient\'s age >53 | No spur or spur ≤6.5 mm | Duration of symptoms <12 months | Probability of | ||
---|---|---|---|---|---|
No change | Partial remission | Complete remission | |||
1 | 1 | 1 | 0.07 (0.03–0.14) | 0.38 (0.22–0.58) | 0.55 (0.36–0.73) |
1 | 1 | 0 | 0.13 (0.07–0.28) | 0.37 (0.21–0.57) | 0.50 (0.30–0.70) |
1 | 0 | 1 | 0.15 (0.06–0.24) | 0.53 (0.33–0.72) | 0.32 (0.17–0.53) |
1 | 0 | 0 | 0.25 (0.13–0.45) | 0.48 (0.27–0.69) | 0.27 (0.13–0.48) |
0 | 1 | 1 | 0.17 (0.10–0.31) | 0.33 (0.19–0.50) | 0.50 (0.33–0.66) |
0 | 1 | 0 | 0.34 (0.20–0.53) | 0.40 (0.24–0.59) | 0.26 (0.13–0.45) |
0 | 0 | 1 | 0.30 (0.20–0.46) | 0.29 (0.18–0.43) | 0.41 (0.27–0.56) |
0 | 0 | 0 | 0.51 (0.35–0.69) | 0.31 (0.17–0.48) | 0.18 (0.09–0.33) |
Probabilities (95%‐CI) for NC, PR and CR calculated by polytomous logistic regression in dependence of the risk factors age, spur length, and duration of symptoms before LD‐EBRT according to Hermann et al. in a collective of 285 heels treated with 6 × 1/6 × 0.5 Gy (taken from [38]).
In modern radiotherapeutic departments, X‐ray sources are less and less available. This is why nowadays most patients are treated with linear accelerators, which were initially developed for the treatment of oncological diseases. However, these machines can be used in the treatment of benign diseases without any modifications or problems. Due to the high efforts in physical, technical, and organizational quality assurances for the operation of an accelerator or an X-ray source, the concentration on accelerators and their use for all indications is recommended.
For irradiation of the heel, the patient has to be placed on the treatment couch with the feet toward the gantry of the accelerator (so‐called “feet first”). Two different patient positions are widely used. He can be placed in supine position, with the irradiated leg is stretched out, while the other leg is angled. Another option is to place the patient in a lateral decubitus position on the side of the involved heel. Again, the symptomatic leg is stretched, while the contralateral leg is bent, with a cushion placed beneath the knee. Using X‐rays, the ipsilateral knee is bent by 90% and the foot is positioned on the treatment table. One anterior‐posterior (AP) beam is usually applied in this technique.
For the treatment itself, there are also two different options. Irradiation may be given as a single stationary field (SSD 100cm by convention). Alternatively, parallel opposing fields from 0° and 180° gantry position (in decubitus position) or lateral opposing fields (90° and 270° in supine position) are also applicable but take a little bit longer in daily clinical practice. The hypothetical advantage of using two opposing fields is a uniform dose distribution in the entire beam path in the calcaneus (Figure 1). However, there has never been a clinical proof, whether this theoretical assumption translates into any clinical advantage for the patient. When applying opposing fields, the dose is specified according to the ICRU 50 report, normally in the center of the calcaneus.
Dose distribution of two different treatment techniques generated in a treatment planning system (XIO®). In A and B just one single 6 MV photon field (8 × 8 cm) is applied, while C and D shows the dose distribution with two opposing fields from 0 and 180°. In the upper row, the so‐called “beams eye views” are given, while in the lower row the respective dose distributions on an axial CT scan directly at the calcaneal insertion are shown. Note the more uniform dose distribution with opposing fields. The 95% isodose is given as a green line (2.85 Gy). This dose encompasses larger parts of the calcaneal bone in D (opposing fields) than in B (single field). More information is given in Section 2.4.
A third option is the so‐called “plantar field” with the patient lying in prone position. A single field is positioned directly over the plantar insertion/calcaneus, potentially with rotations of the patient table and the gantry to compensate for inclinations of the patients surface in the irradiated field. However, this technique is regarded problematic when using linear accelerators due to the dose build‐up effect in the critical tissue depth. This problem is illustrated in Figure 2: photons with 6 MV reach just the half of the prescribed dose at the skin level, 100% is reached at 1.5 cm tissue depth. This would result in an insufficient dose in the critical structures (plantar fascia and heel spur). To overcome this problem, a silicone flap of about 1 cm diameter must be positioned on the skin before radiation.
Depth curves of different megavoltage energies. Blue 6 MV photons, red 15 MV photons. At the surface of the body/skin (depth 0 mm), only half (or even less with 15 MV) of the prescribed dose is applied. By physical interactions between photons and the tissue/water, there is a steep increase in dose. A 100% is reached at 1.5 cm depth with 6 MV and at about 3 cm depth with 15 MV. KV‐radiation reaches the maximum dose directly under the surface/skin (not shown). More information is given in Section 2.4.
Patients are often sent to the radiotherapist after a long unsuccessful history of diverse conservative treatments. The reason for this is a widespread fear among general practitioners that LD‐EBRT might be associated with severe side effects and risks. These fears are not substantiated, as reactions of the nerves or vessels require much higher doses than used for LD‐EBRT. For example, a dose of 45 Gy in normofractionated oncological therapy is considered to be safe for the spinal cord and therefore daily clinical practice [44]. Peripheral nerves are even more radioresistant. Acute or chronic side‐effects have never been reported in all contemporary studies on LD‐EBRT.
Acute side effects are negligible, as very low doses of ionizing radiation (in comparison with oncological treatments) are applied to a distal extremity. The total dose of LD‐EBRT with 3 or 6 Gy is far too low to cause any acute or late reactions on the skin overlaying the calcaneus. During normofractionated EBRT (single doses of 1.8–2 Gy, treatment on 5 days a week) erythema and mild edema develop at about 30 Gy [45]. Hyperpigmentation occurs at about 45 Gy, moist epitheliolyses at about 50 Gy. A 50–60 Gy might cause telangiectasias years after the therapy. This is why there is no report on acute treatment side effects in LD‐EBRT until now to the best of our knowledge.
About one‐third of the patients might experience a slight increase in pain during LD‐EBRT. In the randomized trial by Heydt et al. this phenomenon was seen in 26% (during 6 × 0.5 Gy) vs. 29% (6 × 1 Gy) [30]. It does not seem to be correlated with treatment outcome; further detailed information is given in Section 2.3.4.
The dose scattered to the male gonads is somewhat higher than to the ovaries. Jansen et al. calculated for 6 × 0.5 Gy about 1.5 mSv received by the testes and 0.75 mSv to the ovaries [46]. Comparable results have repeatedly been measured in the past [47, 48].
Taken together, the dose received by the gonads is insignificant. As the distal extremity is irradiated, scattered dose to the gonads is comparable to normal diagnostic radiological imaging [49]. The hereditary effects of these doses are very small and very likely negligible [46].
Although spermatogonial cells are very radiosensitive, a single dose of at least 100 mSv is needed to induce a temporary failure of spermatogenesis [50]. A single dose of 1000 mSv (equivalent to 1 Gy photon irradiation) results in an azoospermia for 9–18 months [51]. Interestingly, fractionated doses harm these cells even more. A temporary oligospermia is reported after receiving several fractions up to a cumulative dose of 160 mSv [52]. An azoospermia lasting for 14–22 months has been reported for fractionated doses of 620–860 mSv [53]. The actually during LD‐EBRT received testicular dose is about 100 times smaller than the lowest dose causing temporary changes in testicular tissues.
The dose to the testicles can be further reduced by utilizing a special testicular shielding. However, clinically meaningful dose reductions have been only measured in MV treatment of subdiaphragmatic/pelvine lymphatic regions or tumors [54, 55].
The mean lethal dose for human oocytes has been estimated at 2 Gy (2000 mSv) [56]. Permanent ovarian failure after radiotherapy is age dependent: in perimenopausal women, a dose of 6 Gy is sufficient [57], while in younger women up to 20 Gy are tolerated. The dose scattered to the ovaries during LD‐EBRT for calcaneodynia cannot cause such sequelae (0.75 mSv).
Naturally, pregnancy has to be excluded in all premenopausal women before beginning with LD‐EBRT, to avoid any risk to the fetus.
So far, no studies with long‐term observation periods have been published, describing a case of malignancy induced by LD‐EBRT for calcaneodynia. However, induction of malignancies is a stochastic effect of ionizing radiation. This means that there is no threshold dose—in contrast for example to the above‐mentioned reactions of the skin. A photon can accidentally trigger a mutation, which in turn leads to tumor formation many years later. The higher the radiation dose, the higher the probability of such an event occurring.
The best available data on tumor induction of full dose EBRT in oncology has been collected in patients treated with breast cancer. Almost 11,000 patients have been followed for over 20 years. The risk of a radiation‐induced tumor was approx. 1% per decade after radiotherapy [58].
To estimate the risk associated with much lower doses of LD‐EBRT, mathematical models on the basis of epidemiological long‐term observations of atomic bomb victims have been developed by the ICRP [59].
Jansen et al. applied the ICRP model on LD‐EBRT of a painful heel spur [46]. Assumed was a single field entering at the foot sole with a size of 8 × 10 cm, 200 kV photons, SSD 40 cm. For an LD‐EBRT series with 6 × 1 Gy the average attributable lifetime risk for induction of a fatal tumor was calculated to be about 0.5 in a thousand patients. An important risk factor for radiogenic‐induced cancer is the patient\'s age by the time the radiation exposure occurs. The risk is already reduced in the 3rd decade of the patient\'s life, it starts to decrease steadily from the age of 40 [60]. Applying these calculations, the estimated lifetime risk per one thousand patients for a fatal tumor accounts for the age of 25 0.6 (male)/0.8 (female), for the age of 50 0.2/0.3, for the age of 75 0.07/0.1 [46].
However, it must be critically noted that this mathematical model was developed for radiation protection and relates to the exposure of complete organ systems with approx. 1 Gy. Therefore, other groups argue that a significantly lower risk of radiogenic cancer induction— approx. ten times less—should be adopted [49, 61]. Furthermore, taken the new standard scheme with 6 × 0.5 Gy into account, these risks are additionally halved.
This risk (max. 1/1000, very likely much lower) must be seen in relation to the tumor risk of the not additionally radiotherapeutical‐treated population. In 2008, the lifetime risk of a man in Germany to suffer from cancer was 50.7% (25.9% to die from malignancy), in women 42.8% and 20.2% respectively [62].
By limiting the application of LD‐EBRT treatment to patients > 30 years of age, an exposure of the juvenile “relatively higher risk” patient population is avoided.
Traditionally target volume definition has been quite large. Field sizes of 12 × 17cm were treated, including the entire dorsal and middle foot, and not just the calcaneus [37, 82] (Figure 3A).
Field definitions in LD‐EBRT of a painful plantar heel spur/fasciitis. (A) traditional field definition including the entire dorsal and middle foot. (B) In randomized trials and large prospective series commonly used field definition encompassing the entire calcaneus, including insertion of the plantar fascia and the Achilles tendon. (C) Proposed small field definition for localized painful plantar fasciitis/plantar spur, encompassing only the painful area with 2 cm margins extending into the neighboring areas (calcaneus, fascia, fat pad).
In the recent randomized trials and prospective observational studies target volume definition was more restricted and confined to the calcaneus (Figure 3B). “The target volume consisted of the calcaneus and the region of the plantar aponeurosis” [26]. “The ventral margin is corresponding to the ventral surface of the calcaneus, the plantar and dorsal margins are surrounding the soft‐tissue border, and the cranial margin is below the ankle” [30]. “Target volume is the calcaneus, normally with a field size of 6 cm × 8 cm” [32]. “The calcaneus and the plantar aponeurosis were included in the target volume” [25].
In a German national survey 2001 on LD‐EBRT of painful heel spurs the target volume definition “large” (dorsal and middle foot) vs. “small” (entire calcaneus) was not correlated with treatment outcome [83]. Consequently, very large field definitions should be regarded as obsolete.
However, as the pathophysiological cause of calcaneodynia is thought to be a localized inflammatory process (see Section 1), it is questionable, whether the entire calcaneus has to be irradiated (as long as there are not a plantar as well as a painful dorsal spurs). There are some clinical data that support a further restriction of target volume definition.
Field sizes have been given in the study by Miszczyk et al. on 327 patients treated with X‐ray beams [39]. Target volume was “… the insertion of the plantar fascia with a calcaneal spur and a reasonable margin. The field size varied from 27 to 150 cm2 (mean 47 cm2).” However, although not explicitly stated, no correlation was found between field size and duration of pain relief after LD‐EBRT. Treatment efficacy in itself was apparently not investigated.
In the above‐mentioned series of 285 heels Hermann et al. analyzed treatment efficacy in dependence of field sizes, too [38]. The mean field size was 74 cm2. No correlation between field size (smaller vs. larger than 74 cm2) with treatment efficacy was found. Further analyses of small fields (< 6 × 6 cm), medium‐sized fields (36–64 cm2) and larger fields revealed no significant differences.
This is why it seems to suffice to encompass the painful region with 2 cm margins extending into the neighboring areas (calcaneus, fascia, fat pad; Figure 3C). However, this recommendation is deducted from pathophysiological considerations and the above‐mentioned case series. A randomized trial is necessary to proof clinical equivalence of a field definition “entire calcaneus” (Figure 3B) vs. “insertion of the plantar fascia” (Figure 3C).
The optimal fractionation schedule has not been elucidated yet. All randomized trial used twice weekly treatments. Only one experimental arm was scheduled three times a week [25]. In a National Survey in Germany with 146 answering institutions, about 45% applied two fractions and 37.5% three fractions weekly [83].
Interestingly, in the landmark study by von Pannewitz a fractionation schedule of only once per week was established [34]. Until now, there is no proof of a higher efficacy applying LD‐EBRT twice or three times per week.
In radiotherapy of another benign disease (endocrine orbitopathy) a 1 Gy per week over 20 weeks schedule was more effective than the standard schedules (10 × 2 Gy or 10 × 1 Gy every working day) [84]. Although other immunological mechanisms cause endocrine orbitopathy in comparison with plantar fasciitis, there is sufficient clinical evidence to test in a randomized trial different fractionation schedules (twice a week vs. once a week, possibly thrice a week).
Other therapies than LD‐EBRT have been applied in painful heel spur. In the following, just a rough overview can be given.
Different kinds of insoles and foot orthoses have been developed. The goal was to reduce plantar contact pressure and to distribute the pressure uniformly over the whole rearfoot [63]. Magnetic insoles do not seem to provide additional benefit [64]. As a short‐term treatment, low‐Dye taping techniques are often used. However, in a randomized trial only a modest improvement in ‘first‐step’ pain was seen in comparison with sham‐intervention [65].
Manual stretching is often recommended. A systematic review of six studies found only statistically significant differences in comparison with the control in one study combining calf muscle and plantar fascia stretches [66].
Several trials have investigated acupuncture. A systematic review from 2010 showed (limited) evidence for the effectiveness [67]. A randomized trial published in 2014 recruited 84 patients [68]. The authors concluded, that “dry needling provided statistically significant reductions in plantar heel pain, but the magnitude of this effect should be considered against the frequency of minor transitory adverse events.”
Ultrasound therapy has led to questionable results [69], but a randomized trial on cryo‐ultrasound with about 100 patients published in 2014 showed good effectiveness [70].
Low‐level laser light (635 nm), given twice a week for a total of six applications, reduced in a randomized trial VAS scores significantly after 8 weeks in comparison with placebo [71]. However, the study comprised of just 69 patients; other similar studies have not been reported so far.
Extracorporeal shock waves are widely applied. Three metaanalyses comprising at least five randomized trials found significant short‐term pain relief and improved functional outcomes for this therapeutic option [72–74]. Another study compared the analgesic efficacy of ultrasound and shock wave therapy in 47 patients [75]. The results suggested that the shock wave therapy had greater analgesic efficacy.
Another basic approach is the oral administration of nonsteroidal anti‐inflammatory drugs (NSAID) to achieve a symptomatic relief. Injections into the painful area are also recommended. A recent review summarized ten randomized trials on corticosteroid injections into the plantar fascia [76]. A significant effect of the steroids on the pain has been shown. However, it was usually short‐term, lasting 4–12 weeks in duration. No advantage of ultrasound‐guided injection techniques in comparison with palpation guidance was found, and no superiority of one type of corticosteroid over another was seen. A longer lasting pain relief has been suggested by a small randomized trial of botulinum toxin injections [77]. Another option is the injection of autologous platelet‐rich plasma. A recent review identified three randomized trials, all showing promising results [78]. However, a very small trial challenged this method of plasma preparation, as the same clinical effectivity was observed after the injection of whole blood [79].
Different surgical approaches have been developed. Releases of the plantar fascia are done, in some studies combined with a spur resection [80]. Due to a probably faster recovery after surgery with comparable functional results endoscopic procedures are recommended nowadays [81]. Surgery is usually indicated after failure of conservative therapies as the ultimate “salvage‐therapy.”
There is only a limited amount of studies randomizing patients between LD‐EBRT and the above‐mentioned alternative therapies.
Canyilmaz et al. randomized 123 patients between LD‐EBRT (6 × 1 Gy, three times a week) and 1 ml injection of 40 mg methylprednisolone and 0.5 ml 60 mg 1% lidocaine under the guidance of palpation [85]. After 3 and 6 months, VAS values and CS‐scores were compared between both groups. After 3 months, the results in the radiotherapy arm were significantly superior compared with those after injections.
To corroborate these findings, similar studies should be conducted. Furthermore, more studies randomizing LD‐EBRT against other therapies (e.g. extracorporeal shock waves) are needed. A minimum size of 50 patients per treatment arm should be assured to gain more statistically relevant results. Recruiting patients without prior excessive other therapies for these studies would be optimal.
The goal must be an evidence‐based algorithm defining the therapeutic sequence of the different conservative treatment modalities for plantar fasciitis.
LD‐EBRT for painful plantar fasciitis/heel spur is an effective and safe treatment option for patients over 30 years of age and after exclusion of pregnancy. A fractionation of 6 × 0.5 Gy twice weekly up to a total dose of 3 Gy is currently recommended. In the case of an insufficient response a second course can be offered to the patient.
Randomized trials on target volume definition and further optimization of LD‐EBRT fractionation are currently in the process of planning. Further trials to compare the different conservative therapies for plantar fasciitis with each other are necessary to allow the development of an evidence‐based treatment algorithm.
This chapter is dedicated to Professor Gisela Hermann‐Brennecke on the occasion of her 70th birthday.
AP | anterior‐posterior |
CI | confidence interval |
CR | complete remission |
CS | Calcaneodynia score |
Cu | chemical element symbol for copper |
EC | endothelial cells |
GCG‐BD | German Cooperative Group on Radiotherapy for Benign Diseases |
Gy | Gray |
ICRP | International Commission on Radiological Protection |
IL | interleukin |
iNOS | inducible nitric oxide synthases |
KV | kilovoltage |
LD‐EBRT | low dose external beam radiotherapy |
mA | milliampere |
mRNA | messenger ribonuclein acid |
mSv | milliSievert |
MV | megavoltage |
NC | no change |
NF‐κB | nuclear factor kappa B |
NO | nitric oxide |
NSAID | non‐steroidal anti‐inflammatory drug |
PBMC | peripheral blood mononuclear cells |
PR | partial remission |
QOL | quality of life |
ROS | reactive oxygen species |
SSD | skin‐to‐source distance |
TGF‐β1 | transforming growth factor β1 |
VAS | visual analogue scale |
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His studies in robotics lead him not only to a PhD degree but also inspired him to co-found and build the International Journal of Advanced Robotic Systems - world's first Open Access journal in the field of robotics.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"441",title:"Ph.D.",name:"Jaekyu",middleName:null,surname:"Park",slug:"jaekyu-park",fullName:"Jaekyu Park",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/441/images/1881_n.jpg",biography:null,institutionString:null,institution:{name:"LG Corporation (South Korea)",country:{name:"Korea, South"}}},{id:"465",title:"Dr.",name:"Christian",middleName:null,surname:"Martens",slug:"christian-martens",fullName:"Christian Martens",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Rheinmetall (Germany)",country:{name:"Germany"}}},{id:"479",title:"Dr.",name:"Valentina",middleName:null,surname:"Colla",slug:"valentina-colla",fullName:"Valentina Colla",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/479/images/358_n.jpg",biography:null,institutionString:null,institution:{name:"Sant'Anna School of Advanced Studies",country:{name:"Italy"}}},{id:"494",title:"PhD",name:"Loris",middleName:null,surname:"Nanni",slug:"loris-nanni",fullName:"Loris Nanni",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/494/images/system/494.jpg",biography:"Loris Nanni received his Master Degree cum laude on June-2002 from the University of Bologna, and the April 26th 2006 he received his Ph.D. in Computer Engineering at DEIS, University of Bologna. On September, 29th 2006 he has won a post PhD fellowship from the university of Bologna (from October 2006 to October 2008), at the competitive examination he was ranked first in the industrial engineering area. He extensively served as referee for several international journals. He is author/coauthor of more than 100 research papers. He has been involved in some projects supported by MURST and European Community. His research interests include pattern recognition, bioinformatics, and biometric systems (fingerprint classification and recognition, signature verification, face recognition).",institutionString:null,institution:null},{id:"496",title:"Dr.",name:"Carlos",middleName:null,surname:"Leon",slug:"carlos-leon",fullName:"Carlos Leon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Seville",country:{name:"Spain"}}},{id:"512",title:"Dr.",name:"Dayang",middleName:null,surname:"Jawawi",slug:"dayang-jawawi",fullName:"Dayang Jawawi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Technology Malaysia",country:{name:"Malaysia"}}},{id:"528",title:"Dr.",name:"Kresimir",middleName:null,surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/528/images/system/528.jpg",biography:"K. Delac received his B.Sc.E.E. degree in 2003 and is currentlypursuing a Ph.D. degree at the University of Zagreb, Faculty of Electrical Engineering andComputing. His current research interests are digital image analysis, pattern recognition andbiometrics.",institutionString:null,institution:{name:"University of Zagreb",country:{name:"Croatia"}}},{id:"557",title:"Dr.",name:"Andon",middleName:"Venelinov",surname:"Topalov",slug:"andon-topalov",fullName:"Andon Topalov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/557/images/1927_n.jpg",biography:"Dr. Andon V. Topalov received the MSc degree in Control Engineering from the Faculty of Information Systems, Technologies, and Automation at Moscow State University of Civil Engineering (MGGU) in 1979. He then received his PhD degree in Control Engineering from the Department of Automation and Remote Control at Moscow State Mining University (MGSU), Moscow, in 1984. From 1985 to 1986, he was a Research Fellow in the Research Institute for Electronic Equipment, ZZU AD, Plovdiv, Bulgaria. In 1986, he joined the Department of Control Systems, Technical University of Sofia at the Plovdiv campus, where he is presently a Full Professor. He has held long-term visiting Professor/Scholar positions at various institutions in South Korea, Turkey, Mexico, Greece, Belgium, UK, and Germany. And he has coauthored one book and authored or coauthored more than 80 research papers in conference proceedings and journals. His current research interests are in the fields of intelligent control and robotics.",institutionString:null,institution:{name:"Technical University of Sofia",country:{name:"Bulgaria"}}},{id:"585",title:"Prof.",name:"Munir",middleName:null,surname:"Merdan",slug:"munir-merdan",fullName:"Munir Merdan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/585/images/system/585.jpg",biography:"Munir Merdan received the M.Sc. degree in mechanical engineering from the Technical University of Sarajevo, Bosnia and Herzegovina, in 2001, and the Ph.D. degree in electrical engineering from the Vienna University of Technology, Vienna, Austria, in 2009.Since 2005, he has been at the Automation and Control Institute, Vienna University of Technology, where he is currently a Senior Researcher. His research interests include the application of agent technology for achieving agile control in the manufacturing environment.",institutionString:null,institution:null},{id:"605",title:"Prof",name:"Dil",middleName:null,surname:"Hussain",slug:"dil-hussain",fullName:"Dil Hussain",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/605/images/system/605.jpg",biography:"Dr. Dil Muhammad Akbar Hussain is a professor of Electronics Engineering & Computer Science at the Department of Energy Technology, Aalborg University Denmark. Professor Akbar has a Master degree in Digital Electronics from Govt. College University, Lahore Pakistan and a P-hD degree in Control Engineering from the School of Engineering and Applied Sciences, University of Sussex United Kingdom. Aalborg University has Two Satellite Campuses, one in Copenhagen (Aalborg University Copenhagen) and the other in Esbjerg (Aalborg University Esbjerg).\n· He is a member of prestigious IEEE (Institute of Electrical and Electronics Engineers), and IAENG (International Association of Engineers) organizations. \n· He is the chief Editor of the Journal of Software Engineering.\n· He is the member of the Editorial Board of International Journal of Computer Science and Software Technology (IJCSST) and International Journal of Computer Engineering and Information Technology. \n· He is also the Editor of Communication in Computer and Information Science CCIS-20 by Springer.\n· Reviewer For Many Conferences\nHe is the lead person in making collaboration agreements between Aalborg University and many universities of Pakistan, for which the MOU’s (Memorandum of Understanding) have been signed.\nProfessor Akbar is working in Academia since 1990, he started his career as a Lab demonstrator/TA at the University of Sussex. After finishing his P. hD degree in 1992, he served in the Industry as a Scientific Officer and continued his academic career as a visiting scholar for a number of educational institutions. In 1996 he joined National University of Science & Technology Pakistan (NUST) as an Associate Professor; NUST is one of the top few universities in Pakistan. In 1999 he joined an International Company Lineo Inc, Canada as Manager Compiler Group, where he headed the group for developing Compiler Tool Chain and Porting of Operating Systems for the BLACKfin processor. The processor development was a joint venture by Intel and Analog Devices. In 2002 Lineo Inc., was taken over by another company, so he joined Aalborg University Denmark as an Assistant Professor.\nProfessor Akbar has truly a multi-disciplined career and he continued his legacy and making progress in many areas of his interests both in teaching and research. He has contributed in stochastic estimation of control area especially, in the Multiple Target Tracking and Interactive Multiple Model (IMM) research, Ball & Beam Control Problem, Robotics, Levitation Control. He has contributed in developing Algorithms for Fingerprint Matching, Computer Vision and Face Recognition. He has been supervising Pattern Recognition, Formal Languages and Distributed Processing projects for several years. He has reviewed many books on Management, Computer Science. Currently, he is an active and permanent reviewer for many international conferences and symposia and the program committee member for many international conferences.\nIn teaching he has taught the core computer science subjects like, Digital Design, Real Time Embedded System Programming, Operating Systems, Software Engineering, Data Structures, Databases, Compiler Construction. 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Radiotherapy and Nuclear Medicine Technology has always been my aspiration and my life. As years passed I accumulated a tremendous amount of skills and knowledge in Radiotherapy and Nuclear Medicine, Conventional Radiology, Radiation Protection, Bioinformatics Technology, PACS, Image processing, clinically and lecturing that will enable me to provide a valuable service to the community as a Researcher and Consultant in this field. My method of translating this into day to day in clinical practice is non-exhaustible and my habit of exchanging knowledge and expertise with others in those fields is the code and secret of success.",institutionString:null,institution:{name:"Majmaah University",country:{name:"Saudi Arabia"}}},{id:"313277",title:"Dr.",name:"Bartłomiej",middleName:null,surname:"Płaczek",slug:"bartlomiej-placzek",fullName:"Bartłomiej Płaczek",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/313277/images/system/313277.jpg",biography:"Bartłomiej Płaczek, MSc (2002), Ph.D. (2005), Habilitation (2016), is a professor at the University of Silesia, Institute of Computer Science, Poland, and an expert from the National Centre for Research and Development. His research interests include sensor networks, smart sensors, intelligent systems, and image processing with applications in healthcare and medicine. He is the author or co-author of more than seventy papers in peer-reviewed journals and conferences as well as the co-author of several books. He serves as a reviewer for many scientific journals, international conferences, and research foundations. Since 2010, Dr. Placzek has been a reviewer of grants and projects (including EU projects) in the field of information technologies.",institutionString:"University of Silesia",institution:{name:"University of Silesia",country:{name:"Poland"}}},{id:"35000",title:"Prof.",name:"Ulrich H.P",middleName:"H.P.",surname:"Fischer",slug:"ulrich-h.p-fischer",fullName:"Ulrich H.P Fischer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/35000/images/3052_n.jpg",biography:"Academic and Professional Background\nUlrich H. P. has Diploma and PhD degrees in Physics from the Free University Berlin, Germany. He has been working on research positions in the Heinrich-Hertz-Institute in Germany. Several international research projects has been performed with European partners from France, Netherlands, Norway and the UK. He is currently Professor of Communications Systems at the Harz University of Applied Sciences, Germany.\n\nPublications and Publishing\nHe has edited one book, a special interest book about ‘Optoelectronic Packaging’ (VDE, Berlin, Germany), and has published over 100 papers and is owner of several international patents for WDM over POF key elements.\n\nKey Research and Consulting Interests\nUlrich’s research activity has always been related to Spectroscopy and Optical Communications Technology. Specific current interests include the validation of complex instruments, and the application of VR technology to the development and testing of measurement systems. He has been reviewer for several publications of the Optical Society of America\\'s including Photonics Technology Letters and Applied Optics.\n\nPersonal Interests\nThese include motor cycling in a very relaxed manner and performing martial arts.",institutionString:null,institution:{name:"Charité",country:{name:"Germany"}}},{id:"341622",title:"Ph.D.",name:"Eduardo",middleName:null,surname:"Rojas Alvarez",slug:"eduardo-rojas-alvarez",fullName:"Eduardo Rojas Alvarez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/341622/images/15892_n.jpg",biography:null,institutionString:null,institution:{name:"University of Cuenca",country:{name:"Ecuador"}}},{id:"215610",title:"Prof.",name:"Muhammad",middleName:null,surname:"Sarfraz",slug:"muhammad-sarfraz",fullName:"Muhammad Sarfraz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/215610/images/system/215610.jpeg",biography:"Muhammad Sarfraz is a professor in the Department of Information Science, Kuwait University. 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Prof. Sarfraz is also an editor-in-chief and editor of various international journals.",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"32650",title:"Prof.",name:"Lukas",middleName:"Willem",surname:"Snyman",slug:"lukas-snyman",fullName:"Lukas Snyman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/32650/images/4136_n.jpg",biography:"Lukas Willem Snyman received his basic education at primary and high schools in South Africa, Eastern Cape. He enrolled at today's Nelson Metropolitan University and graduated from this university with a BSc in Physics and Mathematics, B.Sc Honors in Physics, MSc in Semiconductor Physics, and a Ph.D. in Semiconductor Physics in 1987. After his studies, he chose an academic career and devoted his energy to the teaching of physics to first, second, and third-year students. After positions as a lecturer at the University of Port Elizabeth, he accepted a position as Associate Professor at the University of Pretoria, South Africa.\r\n\r\nIn 1992, he motivates the concept of 'television and computer-based education” as means to reach large student numbers with only the best of teaching expertise and publishes an article on the concept in the SA Journal of Higher Education of 1993 (and later in 2003). The University of Pretoria subsequently approved a series of test projects on the concept with outreach to Mamelodi and Eerste Rust in 1993. In 1994, the University established a 'Unit for Telematic Education ' as a support section for multiple faculties at the University of Pretoria. In subsequent years, the concept of 'telematic education” subsequently becomes well established in academic circles in South Africa, grew in popularity, and is adopted by many universities and colleges throughout South Africa as a medium of enhancing education and training, as a method to reaching out to far out communities, and as a means to enhance study from the home environment.\r\n\r\nProfessor Snyman in subsequent years pursued research in semiconductor physics, semiconductor devices, microelectronics, and optoelectronics.\r\n\r\nIn 2000 he joined the TUT as a full professor. Here served for a period as head of the Department of Electronic Engineering. Here he makes contributions to solar energy development, microwave and optoelectronic device development, silicon photonics, as well as contributions to new mobile telecommunication systems and network planning in SA.\r\n\r\nCurrently, he teaches electronics and telecommunications at the TUT to audiences ranging from first-year students to Ph.D. level.\r\n\r\nFor his research in the field of 'Silicon Photonics” since 1990, he has published (as author and co-author) about thirty internationally reviewed articles in scientific journals, contributed to more than forty international conferences, about 25 South African provisional patents (as inventor and co-inventor), 8 PCT international patent applications until now. Of these, two USA patents applications, two European Patents, two Korean patents, and ten SA patents have been granted. A further 4 USA patents, 5 European patents, 3 Korean patents, 3 Chinese patents, and 3 Japanese patents are currently under consideration.\r\n\r\nRecently he has also published an extensive scholarly chapter in an internet open access book on 'Integrating Microphotonic Systems and MOEMS into standard Silicon CMOS Integrated circuitry”.\r\n\r\nFurthermore, Professor Snyman recently steered a new initiative at the TUT by introducing a 'Laboratory for Innovative Electronic Systems ' at the Department of Electrical Engineering. The model of this laboratory or center is to primarily combine outputs as achieved by high-level research with lower-level system development and entrepreneurship in a technical university environment. Students are allocated to projects at different levels with PhDs and Master students allocated to the generation of new knowledge and new technologies, while students at the diploma and Baccalaureus level are allocated to electronic systems development with a direct and a near application for application in industry or the commercial and public sectors in South Africa.\r\n\r\nProfessor Snyman received the WIRSAM Award of 1983 and the WIRSAM Award in 1985 in South Africa for best research papers by a young scientist at two international conferences on electron microscopy in South Africa. He subsequently received the SA Microelectronics Award for the best dissertation emanating from studies executed at a South African university in the field of Physics and Microelectronics in South Africa in 1987. In October of 2011, Professor Snyman received the prestigious Institutional Award for 'Innovator of the Year” for 2010 at the Tshwane University of Technology, South Africa. This award was based on the number of patents recognized and granted by local and international institutions as well as for his contributions concerning innovation at the TUT.",institutionString:null,institution:{name:"University of South Africa",country:{name:"South Africa"}}},{id:"317279",title:"Mr.",name:"Ali",middleName:"Usama",surname:"Syed",slug:"ali-syed",fullName:"Ali Syed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/317279/images/16024_n.png",biography:"A creative, talented, and innovative young professional who is dedicated, well organized, and capable research fellow with two years of experience in graduate-level research, published in engineering journals and book, with related expertise in Bio-robotics, equally passionate about the aesthetics of the mechanical and electronic system, obtained expertise in the use of MS Office, MATLAB, SolidWorks, LabVIEW, Proteus, Fusion 360, having a grasp on python, C++ and assembly language, possess proven ability in acquiring research grants, previous appointments with social and educational societies with experience in administration, current affiliations with IEEE and Web of Science, a confident presenter at conferences and teacher in classrooms, able to explain complex information to audiences of all levels.",institutionString:null,institution:{name:"Air University",country:{name:"Pakistan"}}},{id:"75526",title:"Ph.D.",name:"Zihni Onur",middleName:null,surname:"Uygun",slug:"zihni-onur-uygun",fullName:"Zihni Onur Uygun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/75526/images/12_n.jpg",biography:"My undergraduate education and my Master of Science educations at Ege University and at Çanakkale Onsekiz Mart University have given me a firm foundation in Biochemistry, Analytical Chemistry, Biosensors, Bioelectronics, Physical Chemistry and Medicine. After obtaining my degree as a MSc in analytical chemistry, I started working as a research assistant in Ege University Medical Faculty in 2014. In parallel, I enrolled to the MSc program at the Department of Medical Biochemistry at Ege University to gain deeper knowledge on medical and biochemical sciences as well as clinical chemistry in 2014. In my PhD I deeply researched on biosensors and bioelectronics and finished in 2020. Now I have eleven SCI-Expanded Index published papers, 6 international book chapters, referee assignments for different SCIE journals, one international patent pending, several international awards, projects and bursaries. In parallel to my research assistant position at Ege University Medical Faculty, Department of Medical Biochemistry, in April 2016, I also founded a Start-Up Company (Denosens Biotechnology LTD) by the support of The Scientific and Technological Research Council of Turkey. Currently, I am also working as a CEO in Denosens Biotechnology. The main purposes of the company, which carries out R&D as a research center, are to develop new generation biosensors and sensors for both point-of-care diagnostics; such as glucose, lactate, cholesterol and cancer biomarker detections. My specific experimental and instrumental skills are Biochemistry, Biosensor, Analytical Chemistry, Electrochemistry, Mobile phone based point-of-care diagnostic device, POCTs and Patient interface designs, HPLC, Tandem Mass Spectrometry, Spectrophotometry, ELISA.",institutionString:null,institution:{name:"Ege University",country:{name:"Turkey"}}},{id:"267434",title:"Dr.",name:"Rohit",middleName:null,surname:"Raja",slug:"rohit-raja",fullName:"Rohit Raja",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/267434/images/system/267434.jpg",biography:"Dr. Rohit Raja received Ph.D. in Computer Science and Engineering from Dr. CVRAMAN University in 2016. His main research interest includes Face recognition and Identification, Digital Image Processing, Signal Processing, and Networking. Presently he is working as Associate Professor in IT Department, Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur (CG), India. He has authored several Journal and Conference Papers. He has good Academics & Research experience in various areas of CSE and IT. He has filed and successfully published 27 Patents. He has received many time invitations to be a Guest at IEEE Conferences. He has published 100 research papers in various International/National Journals (including IEEE, Springer, etc.) and Proceedings of the reputed International/ National Conferences (including Springer and IEEE). He has been nominated to the board of editors/reviewers of many peer-reviewed and refereed Journals (including IEEE, Springer).",institutionString:"Guru Ghasidas Vishwavidyalaya",institution:{name:"Guru Ghasidas Vishwavidyalaya",country:{name:"India"}}},{id:"246502",title:"Dr.",name:"Jaya T.",middleName:"T",surname:"Varkey",slug:"jaya-t.-varkey",fullName:"Jaya T. Varkey",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246502/images/11160_n.jpg",biography:"Jaya T. Varkey, PhD, graduated with a degree in Chemistry from Cochin University of Science and Technology, Kerala, India. She obtained a PhD in Chemistry from the School of Chemical Sciences, Mahatma Gandhi University, Kerala, India, and completed a post-doctoral fellowship at the University of Minnesota, USA. She is a research guide at Mahatma Gandhi University and Associate Professor in Chemistry, St. Teresa’s College, Kochi, Kerala, India.\nDr. Varkey received a National Young Scientist award from the Indian Science Congress (1995), a UGC Research award (2016–2018), an Indian National Science Academy (INSA) Visiting Scientist award (2018–2019), and a Best Innovative Faculty award from the All India Association for Christian Higher Education (AIACHE) (2019). She Hashas received the Sr. Mary Cecil prize for best research paper three times. She was also awarded a start-up to develop a tea bag water filter. \nDr. Varkey has published two international books and twenty-seven international journal publications. She is an editorial board member for five international journals.",institutionString:"St. Teresa’s College",institution:null},{id:"250668",title:"Dr.",name:"Ali",middleName:null,surname:"Nabipour Chakoli",slug:"ali-nabipour-chakoli",fullName:"Ali Nabipour Chakoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/250668/images/system/250668.jpg",biography:"Academic Qualification:\r\n•\tPhD in Materials Physics and Chemistry, From: Sep. 2006, to: Sep. 2010, School of Materials Science and Engineering, Harbin Institute of Technology, Thesis: Structure and Shape Memory Effect of Functionalized MWCNTs/poly (L-lactide-co-ε-caprolactone) Nanocomposites. Supervisor: Prof. Wei Cai,\r\n•\tM.Sc in Applied Physics, From: 1996, to: 1998, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Determination of Boron in Micro alloy Steels with solid state nuclear track detectors by neutron induced auto radiography, Supervisors: Dr. M. Hosseini Ashrafi and Dr. A. Hosseini.\r\n•\tB.Sc. in Applied Physics, From: 1991, to: 1996, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Design of shielding for Am-Be neutron sources for In Vivo neutron activation analysis, Supervisor: Dr. M. Hosseini Ashrafi.\r\n\r\nResearch Experiences:\r\n1.\tNanomaterials, Carbon Nanotubes, Graphene: Synthesis, Functionalization and Characterization,\r\n2.\tMWCNTs/Polymer Composites: Fabrication and Characterization, \r\n3.\tShape Memory Polymers, Biodegradable Polymers, ORC, Collagen,\r\n4.\tMaterials Analysis and Characterizations: TEM, SEM, XPS, FT-IR, Raman, DSC, DMA, TGA, XRD, GPC, Fluoroscopy, \r\n5.\tInteraction of Radiation with Mater, Nuclear Safety and Security, NDT(RT),\r\n6.\tRadiation Detectors, Calibration (SSDL),\r\n7.\tCompleted IAEA e-learning Courses:\r\nNuclear Security (15 Modules),\r\nNuclear Safety:\r\nTSA 2: Regulatory Protection in Occupational Exposure,\r\nTips & Tricks: Radiation Protection in Radiography,\r\nSafety and Quality in Radiotherapy,\r\nCourse on Sealed Radioactive Sources,\r\nCourse on Fundamentals of Environmental Remediation,\r\nCourse on Planning for Environmental Remediation,\r\nKnowledge Management Orientation Course,\r\nFood Irradiation - Technology, Applications and Good Practices,\r\nEmployment:\r\nFrom 2010 to now: Academic staff, Nuclear Science and Technology Research Institute, Kargar Shomali, Tehran, Iran, P.O. Box: 14395-836.\r\nFrom 1997 to 2006: Expert of Materials Analysis and Characterization. Research Center of Agriculture and Medicine. Rajaeeshahr, Karaj, Iran, P. O. Box: 31585-498.",institutionString:"Atomic Energy Organization of Iran",institution:{name:"Atomic Energy Organization of Iran",country:{name:"Iran"}}},{id:"248279",title:"Dr.",name:"Monika",middleName:"Elzbieta",surname:"Machoy",slug:"monika-machoy",fullName:"Monika Machoy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248279/images/system/248279.jpeg",biography:"Monika Elżbieta Machoy, MD, graduated with distinction from the Faculty of Medicine and Dentistry at the Pomeranian Medical University in 2009, defended her PhD thesis with summa cum laude in 2016 and is currently employed as a researcher at the Department of Orthodontics of the Pomeranian Medical University. She expanded her professional knowledge during a one-year scholarship program at the Ernst Moritz Arndt University in Greifswald, Germany and during a three-year internship at the Technical University in Dresden, Germany. She has been a speaker at numerous orthodontic conferences, among others, American Association of Orthodontics, European Orthodontic Symposium and numerous conferences of the Polish Orthodontic Society. She conducts research focusing on the effect of orthodontic treatment on dental and periodontal tissues and the causes of pain in orthodontic patients.",institutionString:"Pomeranian Medical University",institution:{name:"Pomeranian Medical University",country:{name:"Poland"}}},{id:"252743",title:"Prof.",name:"Aswini",middleName:"Kumar",surname:"Kar",slug:"aswini-kar",fullName:"Aswini Kar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252743/images/10381_n.jpg",biography:"uploaded in cv",institutionString:null,institution:{name:"KIIT University",country:{name:"India"}}},{id:"204256",title:"Dr.",name:"Anil",middleName:"Kumar",surname:"Kumar Sahu",slug:"anil-kumar-sahu",fullName:"Anil Kumar Sahu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204256/images/14201_n.jpg",biography:"I have nearly 11 years of research and teaching experience. I have done my master degree from University Institute of Pharmacy, Pt. Ravi Shankar Shukla University, Raipur, Chhattisgarh India. I have published 16 review and research articles in international and national journals and published 4 chapters in IntechOpen, the world’s leading publisher of Open access books. I have presented many papers at national and international conferences. I have received research award from Indian Drug Manufacturers Association in year 2015. My research interest extends from novel lymphatic drug delivery systems, oral delivery system for herbal bioactive to formulation optimization.",institutionString:null,institution:{name:"Chhattisgarh Swami Vivekanand Technical University",country:{name:"India"}}},{id:"253468",title:"Dr.",name:"Mariusz",middleName:null,surname:"Marzec",slug:"mariusz-marzec",fullName:"Mariusz Marzec",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/253468/images/system/253468.png",biography:"An assistant professor at Department of Biomedical Computer Systems, at Institute of Computer Science, Silesian University in Katowice. Scientific interests: computer analysis and processing of images, biomedical images, databases and programming languages. He is an author and co-author of scientific publications covering analysis and processing of biomedical images and development of database systems.",institutionString:"University of Silesia",institution:{name:"University of Silesia",country:{name:"Poland"}}},{id:"212432",title:"Prof.",name:"Hadi",middleName:null,surname:"Mohammadi",slug:"hadi-mohammadi",fullName:"Hadi Mohammadi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/212432/images/system/212432.jpeg",biography:"Dr. Hadi Mohammadi is a biomedical engineer with hands-on experience in the design and development of many engineering structures and medical devices through various projects that he has been involved in over the past twenty years. Dr. Mohammadi received his BSc. and MSc. degrees in Mechanical Engineering from Sharif University of Technology, Tehran, Iran, and his PhD. degree in Biomedical Engineering (biomaterials) from the University of Western Ontario. He was a postdoctoral trainee for almost four years at University of Calgary and Harvard Medical School. He is an industry innovator having created the technology to produce lifelike synthetic platforms that can be used for the simulation of almost all cardiovascular reconstructive surgeries. He’s been heavily involved in the design and development of cardiovascular devices and technology for the past 10 years. He is currently an Assistant Professor with the University of British Colombia, Canada.",institutionString:"University of British Columbia",institution:{name:"University of British Columbia",country:{name:"Canada"}}},{id:"254463",title:"Prof.",name:"Haisheng",middleName:null,surname:"Yang",slug:"haisheng-yang",fullName:"Haisheng Yang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/254463/images/system/254463.jpeg",biography:"Haisheng Yang, Ph.D., Professor and Director of the Department of Biomedical Engineering, College of Life Science and Bioengineering, Beijing University of Technology. He received his Ph.D. degree in Mechanics/Biomechanics from Harbin Institute of Technology (jointly with University of California, Berkeley). Afterwards, he worked as a Postdoctoral Research Associate in the Purdue Musculoskeletal Biology and Mechanics Lab at the Department of Basic Medical Sciences, Purdue University, USA. He also conducted research in the Research Centre of Shriners Hospitals for Children-Canada at McGill University, Canada. Dr. Yang has over 10 years research experience in orthopaedic biomechanics and mechanobiology of bone adaptation and regeneration. He earned an award from Beijing Overseas Talents Aggregation program in 2017 and serves as Beijing Distinguished Professor.",institutionString:null,institution:{name:"Beijing University of Technology",country:{name:"China"}}},{id:"89721",title:"Dr.",name:"Mehmet",middleName:"Cuneyt",surname:"Ozmen",slug:"mehmet-ozmen",fullName:"Mehmet Ozmen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/89721/images/7289_n.jpg",biography:null,institutionString:null,institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"265335",title:"Mr.",name:"Stefan",middleName:"Radnev",surname:"Stefanov",slug:"stefan-stefanov",fullName:"Stefan Stefanov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/265335/images/7562_n.jpg",biography:null,institutionString:null,institution:{name:"Medical University Plovdiv",country:{name:"Bulgaria"}}},{id:"242893",title:"Ph.D. Student",name:"Joaquim",middleName:null,surname:"De Moura",slug:"joaquim-de-moura",fullName:"Joaquim De Moura",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/242893/images/7133_n.jpg",biography:"Joaquim de Moura received his degree in Computer Engineering in 2014 from the University of A Coruña (Spain). In 2016, he received his M.Sc degree in Computer Engineering from the same university. He is currently pursuing his Ph.D degree in Computer Science in a collaborative project between ophthalmology centers in Galicia and the University of A Coruña. His research interests include computer vision, machine learning algorithms and analysis and medical imaging processing of various kinds.",institutionString:null,institution:{name:"University of A Coruña",country:{name:"Spain"}}},{id:"294334",title:"B.Sc.",name:"Marc",middleName:null,surname:"Bruggeman",slug:"marc-bruggeman",fullName:"Marc Bruggeman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/294334/images/8242_n.jpg",biography:"Chemical engineer graduate, with a passion for material science and specific interest in polymers - their near infinite applications intrigue me. \n\nI plan to continue my scientific career in the field of polymeric biomaterials as I am fascinated by intelligent, bioactive and biomimetic materials for use in both consumer and medical applications.",institutionString:null,institution:null},{id:"255757",title:"Dr.",name:"Igor",middleName:"Victorovich",surname:"Lakhno",slug:"igor-lakhno",fullName:"Igor Lakhno",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255757/images/system/255757.jpg",biography:"Igor Victorovich Lakhno was born in 1971 in Kharkiv (Ukraine). \nMD – 1994, Kharkiv National Medical Univesity.\nOb&Gyn; – 1997, master courses in Kharkiv Medical Academy of Postgraduate Education.\nPh.D. – 1999, Kharkiv National Medical Univesity.\nDSC – 2019, PL Shupik National Academy of Postgraduate Education \nProfessor – 2021, Department of Obstetrics and Gynecology of VN Karazin Kharkiv National University\nHead of Department – 2021, Department of Perinatology, Obstetrics and gynecology of Kharkiv Medical Academy of Postgraduate Education\nIgor Lakhno has been graduated from international training courses on reproductive medicine and family planning held at Debrecen University (Hungary) in 1997. Since 1998 Lakhno Igor has worked as an associate professor in the department of obstetrics and gynecology of VN Karazin National University and an associate professor of the perinatology, obstetrics, and gynecology department of Kharkiv Medical Academy of Postgraduate Education. Since June 2019 he’s been a professor in the department of obstetrics and gynecology of VN Karazin National University and a professor of the perinatology, obstetrics, and gynecology department. He’s affiliated with Kharkiv Medical Academy of Postgraduate Education as a Head of Department from November 2021. Igor Lakhno has participated in several international projects on fetal non-invasive electrocardiography (with Dr. J. A. Behar (Technion), Prof. D. Hoyer (Jena University), and José Alejandro Díaz Méndez (National Institute of Astrophysics, Optics, and Electronics, Mexico). He’s an author of about 200 printed works and there are 31 of them in Scopus or Web of Science databases. Igor Lakhno is a member of the Editorial Board of Reproductive Health of Woman, Emergency Medicine, and Technology Transfer Innovative Solutions in Medicine (Estonia). He is a medical Editor of “Z turbotoyu pro zhinku”. Igor Lakhno is a reviewer of the Journal of Obstetrics and Gynaecology (Taylor and Francis), British Journal of Obstetrics and Gynecology (Wiley), Informatics in Medicine Unlocked (Elsevier), The Journal of Obstetrics and Gynecology Research (Wiley), Endocrine, Metabolic & Immune Disorders-Drug Targets (Bentham Open), The Open Biomedical Engineering Journal (Bentham Open), etc. He’s defended a dissertation for a DSc degree “Pre-eclampsia: prediction, prevention, and treatment”. Three years ago Igor Lakhno has participated in a training course on innovative technologies in medical education at Lublin Medical University (Poland). Lakhno Igor has participated as a speaker in several international conferences and congresses (International Conference on Biological Oscillations April 10th-14th 2016, Lancaster, UK, The 9th conference of the European Study Group on Cardiovascular Oscillations). His main scientific interests: are obstetrics, women’s health, fetal medicine, and cardiovascular medicine. \nIgor Lakhno is a consultant at Kharkiv municipal perinatal center. He’s graduated from training courses on endoscopy in gynecology. He has 28 years of practical experience in the field.",institutionString:null,institution:null},{id:"244950",title:"Dr.",name:"Salvatore",middleName:null,surname:"Di Lauro",slug:"salvatore-di-lauro",fullName:"Salvatore Di Lauro",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0030O00002bSF1HQAW/ProfilePicture%202021-12-20%2014%3A54%3A14.482",biography:"Name:\n\tSALVATORE DI LAURO\nAddress:\n\tHospital Clínico Universitario Valladolid\nAvda Ramón y Cajal 3\n47005, Valladolid\nSpain\nPhone number: \nFax\nE-mail:\n\t+34 983420000 ext 292\n+34 983420084\nsadilauro@live.it\nDate and place of Birth:\nID Number\nMedical Licence \nLanguages\t09-05-1985. Villaricca (Italy)\n\nY1281863H\n474707061\nItalian (native language)\nSpanish (read, written, spoken)\nEnglish (read, written, spoken)\nPortuguese (read, spoken)\nFrench (read)\n\t\t\nCurrent position (title and company)\tDate (Year)\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. Private practise.\t2017-today\n\n2019-today\n\t\n\t\nEducation (High school, university and postgraduate training > 3 months)\tDate (Year)\nDegree in Medicine and Surgery. University of Neaples 'Federico II”\nResident in Opthalmology. Hospital Clinico Universitario Valladolid\nMaster in Vitreo-Retina. IOBA. University of Valladolid\nFellow of the European Board of Ophthalmology. Paris\nMaster in Research in Ophthalmology. University of Valladolid\t2003-2009\n2012-2016\n2016-2017\n2016\n2012-2013\n\t\nEmployments (company and positions)\tDate (Year)\nResident in Ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl.\nFellow in Vitreo-Retina. IOBA. University of Valladolid\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. \n\t2012-2016\n2016-2017\n2017-today\n\n2019-Today\n\n\n\t\nClinical Research Experience (tasks and role)\tDate (Year)\nAssociated investigator\n\n' FIS PI20/00740: DESARROLLO DE UNA CALCULADORA DE RIESGO DE\nAPARICION DE RETINOPATIA DIABETICA BASADA EN TECNICAS DE IMAGEN MULTIMODAL EN PACIENTES DIABETICOS TIPO 1. Grant by: Ministerio de Ciencia e Innovacion \n\n' (BIO/VA23/14) Estudio clínico multicéntrico y prospectivo para validar dos\nbiomarcadores ubicados en los genes p53 y MDM2 en la predicción de los resultados funcionales de la cirugía del desprendimiento de retina regmatógeno. Grant by: Gerencia Regional de Salud de la Junta de Castilla y León.\n' Estudio multicéntrico, aleatorizado, con enmascaramiento doble, en 2 grupos\nparalelos y de 52 semanas de duración para comparar la eficacia, seguridad e inmunogenicidad de SOK583A1 respecto a Eylea® en pacientes con degeneración macular neovascular asociada a la edad' (CSOK583A12301; N.EUDRA: 2019-004838-41; FASE III). Grant by Hexal AG\n\n' Estudio de fase III, aleatorizado, doble ciego, con grupos paralelos, multicéntrico para comparar la eficacia y la seguridad de QL1205 frente a Lucentis® en pacientes con degeneración macular neovascular asociada a la edad. (EUDRACT: 2018-004486-13). Grant by Qilu Pharmaceutical Co\n\n' Estudio NEUTON: Ensayo clinico en fase IV para evaluar la eficacia de aflibercept en pacientes Naive con Edema MacUlar secundario a Oclusion de Vena CenTral de la Retina (OVCR) en regimen de tratamientO iNdividualizado Treat and Extend (TAE)”, (2014-000975-21). Grant by Fundacion Retinaplus\n\n' Evaluación de la seguridad y bioactividad de anillos de tensión capsular en conejo. Proyecto Procusens. Grant by AJL, S.A.\n\n'Estudio epidemiológico, prospectivo, multicéntrico y abierto\\npara valorar la frecuencia de la conjuntivitis adenovírica diagnosticada mediante el test AdenoPlus®\\nTest en pacientes enfermos de conjuntivitis aguda”\\n. National, multicenter study. Grant by: NICOX.\n\nEuropean multicentric trial: 'Evaluation of clinical outcomes following the use of Systane Hydration in patients with dry eye”. Study Phase 4. Grant by: Alcon Labs'\n\nVLPs Injection and Activation in a Rabbit Model of Uveal Melanoma. Grant by Aura Bioscience\n\nUpdating and characterization of a rabbit model of uveal melanoma. Grant by Aura Bioscience\n\nEnsayo clínico en fase IV para evaluar las variantes genéticas de la vía del VEGF como biomarcadores de eficacia del tratamiento con aflibercept en pacientes con degeneración macular asociada a la edad (DMAE) neovascular. Estudio BIOIMAGE. IMO-AFLI-2013-01\n\nEstudio In-Eye:Ensayo clínico en fase IV, abierto, aleatorizado, de 2 brazos,\nmulticçentrico y de 12 meses de duración, para evaluar la eficacia y seguridad de un régimen de PRN flexible individualizado de 'esperar y extender' versus un régimen PRN según criterios de estabilización mediante evaluaciones mensuales de inyecciones intravítreas de ranibizumab 0,5 mg en pacientes naive con neovascularización coriodea secunaria a la degeneración macular relacionada con la edad. CP: CRFB002AES03T\n\nTREND: Estudio Fase IIIb multicéntrico, randomizado, de 12 meses de\nseguimiento con evaluador de la agudeza visual enmascarado, para evaluar la eficacia y la seguridad de ranibizumab 0.5mg en un régimen de tratar y extender comparado con un régimen mensual, en pacientes con degeneración macular neovascular asociada a la edad. CP: CRFB002A2411 Código Eudra CT:\n2013-002626-23\n\n\n\nPublications\t\n\n2021\n\n\n\n\n2015\n\n\n\n\n2021\n\n\n\n\n\n2021\n\n\n\n\n2015\n\n\n\n\n2015\n\n\n2014\n\n\n\n\n2015-16\n\n\n\n2015\n\n\n2014\n\n\n2014\n\n\n\n\n2014\n\n\n\n\n\n\n\n2014\n\nJose Carlos Pastor; Jimena Rojas; Salvador Pastor-Idoate; Salvatore Di Lauro; Lucia Gonzalez-Buendia; Santiago Delgado-Tirado. Proliferative vitreoretinopathy: A new concept of disease pathogenesis and practical\nconsequences. Progress in Retinal and Eye Research. 51, pp. 125 - 155. 03/2016. DOI: 10.1016/j.preteyeres.2015.07.005\n\n\nLabrador-Velandia S; Alonso-Alonso ML; Di Lauro S; García-Gutierrez MT; Srivastava GK; Pastor JC; Fernandez-Bueno I. Mesenchymal stem cells provide paracrine neuroprotective resources that delay degeneration of co-cultured organotypic neuroretinal cultures.Experimental Eye Research. 185, 17/05/2019. DOI: 10.1016/j.exer.2019.05.011\n\nSalvatore Di Lauro; Maria Teresa Garcia Gutierrez; Ivan Fernandez Bueno. Quantification of pigment epithelium-derived factor (PEDF) in an ex vivo coculture of retinal pigment epithelium cells and neuroretina.\nJournal of Allbiosolution. 2019. ISSN 2605-3535\n\nSonia Labrador Velandia; Salvatore Di Lauro; Alonso-Alonso ML; Tabera Bartolomé S; Srivastava GK; Pastor JC; Fernandez-Bueno I. Biocompatibility of intravitreal injection of human mesenchymal stem cells in immunocompetent rabbits. Graefe's archive for clinical and experimental ophthalmology. 256 - 1, pp. 125 - 134. 01/2018. DOI: 10.1007/s00417-017-3842-3\n\n\nSalvatore Di Lauro, David Rodriguez-Crespo, Manuel J Gayoso, Maria T Garcia-Gutierrez, J Carlos Pastor, Girish K Srivastava, Ivan Fernandez-Bueno. A novel coculture model of porcine central neuroretina explants and retinal pigment epithelium cells. Molecular Vision. 2016 - 22, pp. 243 - 253. 01/2016.\n\nSalvatore Di Lauro. Classifications for Proliferative Vitreoretinopathy ({PVR}): An Analysis of Their Use in Publications over the Last 15 Years. Journal of Ophthalmology. 2016, pp. 1 - 6. 01/2016. DOI: 10.1155/2016/7807596\n\nSalvatore Di Lauro; Rosa Maria Coco; Rosa Maria Sanabria; Enrique Rodriguez de la Rua; Jose Carlos Pastor. Loss of Visual Acuity after Successful Surgery for Macula-On Rhegmatogenous Retinal Detachment in a Prospective Multicentre Study. Journal of Ophthalmology. 2015:821864, 2015. 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Cell Tissue Res. 358 - 3, pp. 705 - 716. 2014.\nDOI: 10.1007/s00441-014-1987-5\n\nCarlo De Werra; Salvatore Condurro; Salvatore Tramontano; Mario Perone; Ivana Donzelli; Salvatore Di Lauro; Massimo Di Giuseppe; Rosa Di Micco; Annalisa Pascariello; Antonio Pastore; Giorgio Diamantis; Giuseppe Galloro. Hydatid disease of the liver: thirty years of surgical experience.Chirurgia italiana. 59 - 5, pp. 611 - 636.\n(Italia): 2007. ISSN 0009-4773\n\nChapters in books\n\t\n' Salvador Pastor Idoate; Salvatore Di Lauro; Jose Carlos Pastor Jimeno. PVR: Pathogenesis, Histopathology and Classification. Proliferative Vitreoretinopathy with Small Gauge Vitrectomy. Springer, 2018. ISBN 978-3-319-78445-8\nDOI: 10.1007/978-3-319-78446-5_2. \n\n' Salvatore Di Lauro; Maria Isabel Lopez Galvez. Quistes vítreos en una mujer joven. Problemas diagnósticos en patología retinocoroidea. Sociedad Española de Retina-Vitreo. 2018.\n\n' Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor Jimeno. iOCT in PVR management. OCT Applications in Opthalmology. pp. 1 - 8. INTECH, 2018. DOI: 10.5772/intechopen.78774.\n\n' Rosa Coco Martin; Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor. amponadores, manipuladores y tinciones en la cirugía del traumatismo ocular.Trauma Ocular. Ponencia de la SEO 2018..\n\n' LOPEZ GALVEZ; DI LAURO; CRESPO. OCT angiografia y complicaciones retinianas de la diabetes. PONENCIA SEO 2021, CAPITULO 20. (España): 2021.\n\n' Múltiples desprendimientos neurosensoriales bilaterales en paciente joven. Enfermedades Degenerativas De Retina Y Coroides. SERV 04/2016. \n' González-Buendía L; Di Lauro S; Pastor-Idoate S; Pastor Jimeno JC. Vitreorretinopatía proliferante (VRP) e inflamación: LA INFLAMACIÓN in «INMUNOMODULADORES Y ANTIINFLAMATORIOS: MÁS ALLÁ DE LOS CORTICOIDES. 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The combination of electronics and computer science with biology and medicine has improved patient diagnosis, reduced rehabilitation time, and helped to facilitate a better quality of life. Nowadays, all medical imaging devices, medical instruments, or new laboratory techniques result from the cooperation of specialists in various fields. The series of Biomedical Engineering books covers such areas of knowledge as chemistry, physics, electronics, medicine, and biology. 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Dr. Koprowski has authored more than a hundred research papers with dozens in impact factor (IF) journals and has authored or co-authored six books. Additionally, he is the author of several national and international patents in the field of biomedical devices and imaging. Since 2011, he has been a reviewer of grants and projects (including EU projects) in biomedical engineering.",institutionString:null,institution:{name:"University of Silesia",institutionURL:null,country:{name:"Poland"}}},subseries:[{id:"7",title:"Bioinformatics and Medical Informatics",keywords:"Biomedical Data, Drug Discovery, Clinical Diagnostics, Decoding Human Genome, AI in Personalized Medicine, Disease-prevention Strategies, Big Data Analysis in Medicine",scope:"Bioinformatics aims to help understand the functioning of the mechanisms of living organisms through the construction and use of quantitative tools. The applications of this research cover many related fields, such as biotechnology and medicine, where, for example, Bioinformatics contributes to faster drug design, DNA analysis in forensics, and DNA sequence analysis in the field of personalized medicine. Personalized medicine is a type of medical care in which treatment is customized individually for each patient. Personalized medicine enables more effective therapy, reduces the costs of therapy and clinical trials, and also minimizes the risk of side effects. Nevertheless, advances in personalized medicine would not have been possible without bioinformatics, which can analyze the human genome and other vast amounts of biomedical data, especially in genetics. The rapid growth of information technology enabled the development of new tools to decode human genomes, large-scale studies of genetic variations and medical informatics. The considerable development of technology, including the computing power of computers, is also conducive to the development of bioinformatics, including personalized medicine. In an era of rapidly growing data volumes and ever lower costs of generating, storing and computing data, personalized medicine holds great promises. Modern computational methods used as bioinformatics tools can integrate multi-scale, multi-modal and longitudinal patient data to create even more effective and safer therapy and disease prevention methods. Main aspects of the topic are: Applying bioinformatics in drug discovery and development; Bioinformatics in clinical diagnostics (genetic variants that act as markers for a condition or a disease); Blockchain and Artificial Intelligence/Machine Learning in personalized medicine; Customize disease-prevention strategies in personalized medicine; Big data analysis in personalized medicine; Translating stratification algorithms into clinical practice of personalized medicine.",annualVolume:11403,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/7.jpg",editor:{id:"351533",title:"Dr.",name:"Slawomir",middleName:null,surname:"Wilczynski",fullName:"Slawomir Wilczynski",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035U1loQAC/Profile_Picture_1630074514792",institutionString:null,institution:{name:"Medical University of Silesia",institutionURL:null,country:{name:"Poland"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"5886",title:"Dr.",name:"Alexandros",middleName:"T.",surname:"Tzallas",fullName:"Alexandros Tzallas",profilePictureURL:"https://mts.intechopen.com/storage/users/5886/images/system/5886.png",institutionString:"University of Ioannina, Greece & Imperial College London",institution:{name:"University of Ioannina",institutionURL:null,country:{name:"Greece"}}},{id:"257388",title:"Distinguished Prof.",name:"Lulu",middleName:null,surname:"Wang",fullName:"Lulu Wang",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRX6kQAG/Profile_Picture_1630329584194",institutionString:"Shenzhen Technology University",institution:{name:"Shenzhen Technology University",institutionURL:null,country:{name:"China"}}},{id:"225387",title:"Prof.",name:"Reda R.",middleName:"R.",surname:"Gharieb",fullName:"Reda R. Gharieb",profilePictureURL:"https://mts.intechopen.com/storage/users/225387/images/system/225387.jpg",institutionString:"Assiut University",institution:{name:"Assiut University",institutionURL:null,country:{name:"Egypt"}}}]},{id:"8",title:"Bioinspired Technology and Biomechanics",keywords:"Bioinspired Systems, Biomechanics, Assistive Technology, Rehabilitation",scope:'Bioinspired technologies take advantage of understanding the actual biological system to provide solutions to problems in several areas. Recently, bioinspired systems have been successfully employing biomechanics to develop and improve assistive technology and rehabilitation devices. The research topic "Bioinspired Technology and Biomechanics" welcomes studies reporting recent advances in bioinspired technologies that contribute to individuals\' health, inclusion, and rehabilitation. Possible contributions can address (but are not limited to) the following research topics: Bioinspired design and control of exoskeletons, orthoses, and prostheses; Experimental evaluation of the effect of assistive devices (e.g., influence on gait, balance, and neuromuscular system); Bioinspired technologies for rehabilitation, including clinical studies reporting evaluations; Application of neuromuscular and biomechanical models to the development of bioinspired technology.',annualVolume:11404,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/8.jpg",editor:{id:"144937",title:"Prof.",name:"Adriano",middleName:"De Oliveira",surname:"Andrade",fullName:"Adriano Andrade",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRC8QQAW/Profile_Picture_1625219101815",institutionString:null,institution:{name:"Federal University of Uberlândia",institutionURL:null,country:{name:"Brazil"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"49517",title:"Prof.",name:"Hitoshi",middleName:null,surname:"Tsunashima",fullName:"Hitoshi Tsunashima",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYTP4QAO/Profile_Picture_1625819726528",institutionString:null,institution:{name:"Nihon University",institutionURL:null,country:{name:"Japan"}}},{id:"425354",title:"Dr.",name:"Marcus",middleName:"Fraga",surname:"Vieira",fullName:"Marcus Vieira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003BJSgIQAX/Profile_Picture_1627904687309",institutionString:null,institution:{name:"Universidade Federal de Goiás",institutionURL:null,country:{name:"Brazil"}}},{id:"196746",title:"Dr.",name:"Ramana",middleName:null,surname:"Vinjamuri",fullName:"Ramana Vinjamuri",profilePictureURL:"https://mts.intechopen.com/storage/users/196746/images/system/196746.jpeg",institutionString:"University of Maryland, Baltimore County",institution:{name:"University of Maryland, Baltimore County",institutionURL:null,country:{name:"United States of America"}}}]},{id:"9",title:"Biotechnology - Biosensors, Biomaterials and Tissue Engineering",keywords:"Biotechnology, Biosensors, Biomaterials, Tissue Engineering",scope:"The Biotechnology - Biosensors, Biomaterials and Tissue Engineering topic within the Biomedical Engineering Series aims to rapidly publish contributions on all aspects of biotechnology, biosensors, biomaterial and tissue engineering. We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics can include but are not limited to: Biotechnology such as biotechnological products and process engineering; Biotechnologically relevant enzymes and proteins; Bioenergy and biofuels; Applied genetics and molecular biotechnology; Genomics, transcriptomics, proteomics; Applied microbial and cell physiology; Environmental biotechnology; Methods and protocols. Moreover, topics in biosensor technology, like sensors that incorporate enzymes, antibodies, nucleic acids, whole cells, tissues and organelles, and other biological or biologically inspired components will be considered, and topics exploring transducers, including those based on electrochemical and optical piezoelectric, thermal, magnetic, and micromechanical elements. Chapters exploring biomaterial approaches such as polymer synthesis and characterization, drug and gene vector design, biocompatibility, immunology and toxicology, and self-assembly at the nanoscale, are welcome. Finally, the tissue engineering subcategory will support topics such as the fundamentals of stem cells and progenitor cells and their proliferation, differentiation, bioreactors for three-dimensional culture and studies of phenotypic changes, stem and progenitor cells, both short and long term, ex vivo and in vivo implantation both in preclinical models and also in clinical trials.",annualVolume:11405,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/9.jpg",editor:{id:"126286",title:"Dr.",name:"Luis",middleName:"Jesús",surname:"Villarreal-Gómez",fullName:"Luis Villarreal-Gómez",profilePictureURL:"https://mts.intechopen.com/storage/users/126286/images/system/126286.jpg",institutionString:null,institution:{name:"Autonomous University of Baja California",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"35539",title:"Dr.",name:"Cecilia",middleName:null,surname:"Cristea",fullName:"Cecilia Cristea",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYQ65QAG/Profile_Picture_1621007741527",institutionString:null,institution:{name:"Iuliu Hațieganu University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"40735",title:"Dr.",name:"Gil",middleName:"Alberto Batista",surname:"Gonçalves",fullName:"Gil Gonçalves",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYRLGQA4/Profile_Picture_1628492612759",institutionString:null,institution:{name:"University of Aveiro",institutionURL:null,country:{name:"Portugal"}}},{id:"211725",title:"Associate Prof.",name:"Johann F.",middleName:null,surname:"Osma",fullName:"Johann F. Osma",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSDv7QAG/Profile_Picture_1626602531691",institutionString:null,institution:{name:"Universidad de Los Andes",institutionURL:null,country:{name:"Colombia"}}},{id:"69697",title:"Dr.",name:"Mani T.",middleName:null,surname:"Valarmathi",fullName:"Mani T. Valarmathi",profilePictureURL:"https://mts.intechopen.com/storage/users/69697/images/system/69697.jpg",institutionString:"Religen Inc. | A Life Science Company, United States of America",institution:null},{id:"205081",title:"Dr.",name:"Marco",middleName:"Vinícius",surname:"Chaud",fullName:"Marco Chaud",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSDGeQAO/Profile_Picture_1622624307737",institutionString:null,institution:{name:"Universidade de Sorocaba",institutionURL:null,country:{name:"Brazil"}}}]}]}},libraryRecommendation:{success:null,errors:{},institutions:[]},route:{name:"chapter.detail",path:"/chapters/32917",hash:"",query:{},params:{id:"32917"},fullPath:"/chapters/32917",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)}()