Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
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We wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
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Throughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\n
We wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
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It uses a multidisciplinary approach to examine the complex issues of the transplant process. Written by experts in the field, this volume is suitable for medical specialists and medical students alike.",isbn:"978-1-83962-545-9",printIsbn:"978-1-83962-531-2",pdfIsbn:"978-1-83962-549-7",doi:"10.5772/intechopen.87319",price:119,priceEur:129,priceUsd:155,slug:"organ-donation-and-transplantation",numberOfPages:170,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"6ef47e03cd4e6476946fc28ca51de825",bookSignature:"Vassil Mihaylov",publishedDate:"March 31st 2021",coverURL:"https://cdn.intechopen.com/books/images_new/9524.jpg",numberOfDownloads:3079,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:1,numberOfDimensionsCitationsByBook:0,hasAltmetrics:0,numberOfTotalCitations:1,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"June 12th 2020",dateEndSecondStepPublish:"July 3rd 2020",dateEndThirdStepPublish:"September 1st 2020",dateEndFourthStepPublish:"November 20th 2020",dateEndFifthStepPublish:"January 19th 2021",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"313113",title:"Associate Prof.",name:"Vassil",middleName:null,surname:"Mihaylov",slug:"vassil-mihaylov",fullName:"Vassil Mihaylov",profilePictureURL:"https://mts.intechopen.com/storage/users/313113/images/system/313113.png",biography:"Dr. Vassil Mihaylov received his medical degree from the Medical University, Sofia, Bulgaria, and completed his general surgery residency at the Military Medical Academy, Sofia. He completed a transplant fellowship at Queen Elizabeth Hospital, Birmingham, UK, after which he returned to Sofia as a part of the HPB and transplant team at the Military Medical Academy. Dr. Mihaylov obtained his Ph.D. with a thesis on the surgical aspects of liver transplantation. He was appointed Associate Professor of Surgery in 2017. He has published more than 100 papers in peer-reviewed journals and has given many scientific presentations at international meetings. He is a Fellow of the American College of Surgeons and a member of several professional organizations including the Bulgarian Transplant Society, the European Society for Organ Transplantation (ESOT), International Liver Transplantation Society (ILTS), Society of Laparoscopic Surgeons, and International Hepato-Pancreato-Biliary Association (IHPBA). His clinical and research interests include hepatobiliary and pancreatic surgery, minimally invasive surgery, and liver transplantation.",institutionString:"Military Medical Academy",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Military Medical Academy",institutionURL:null,country:{name:"Bulgaria"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"202",title:"Surgery",slug:"surgery"}],chapters:[{id:"73733",title:"Pathophysiological Changes and Systemic Inflammation in Brain Dead Organ Donors: Effect on Graft Quality",doi:"10.5772/intechopen.94360",slug:"pathophysiological-changes-and-systemic-inflammation-in-brain-dead-organ-donors-effect-on-graft-qual",totalDownloads:429,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Transplantation is the definitive treatment of end-stage organ disease. As the shortage of suitable organs poses its main limitation, the active management of potential organ donors becomes increasingly more important. The majority of solid organs are still obtained from donors after confirmed brain death. Brain death is the complete and irreversible cessation of all brain functions, and triggers a variety of severe pathophysiological changes in cardiovascular, hormonal and metabolic status that can result in organ damage. Moreover, brain death is associated with massive inflammatory response with a cytokine storm and complement activation that increases graft immunogenicity and adversely affects graft survival. Organs from brain-dead donors are more prone to graft dysfunction and rejection when compared to organs obtained from living donors. Brain death is thus believed to be an important risk factor influencing the quality of organs before procurement.",signatures:"Neva Bezeljak and Željka Večerić-Haler",downloadPdfUrl:"/chapter/pdf-download/73733",previewPdfUrl:"/chapter/pdf-preview/73733",authors:[{id:"285874",title:"Prof.",name:"Željka",surname:"Večerić-Haler",slug:"zeljka-veceric-haler",fullName:"Željka Večerić-Haler"},{id:"325667",title:"Mrs.",name:"Neva",surname:"Bezeljak",slug:"neva-bezeljak",fullName:"Neva Bezeljak"}],corrections:null},{id:"74329",title:"Organ Donation and Transplantation in Sub-Saharan Africa: Opportunities and Challenges",doi:"10.5772/intechopen.94986",slug:"organ-donation-and-transplantation-in-sub-saharan-africa-opportunities-and-challenges",totalDownloads:527,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Sub-Saharan Africa (SSA), occupying about 80% of the African continent is a heterogeneous region with estimated population of 1.1 billion people in 47 countries. Most belong to the low resource countries (LRCs). The high prevalence of end-organ diseases of kidney, liver, lung and heart makes provision of organ donation and transplantation necessary. Although kidney and heart transplantations were performed in South Africa in the 1960s, transplant activity in SSA lags behind the developed world. Peculiar challenges militating against successful development of transplant programmes include high cost of treatment, low GDP of most countries, inadequate infrastructural and institutional support, absence of subsidy, poor knowledge of the disease condition, poor accessibility to health-care facilities, religious and trado-cultural practices. Many people in the region patronize alternative healthcare as first choice. Opportunities that if harnessed may alter the unfavorable landscape are: implementation of the 2007 WHO Regional Consultation recommendations for establishment of national legal framework and self-sufficient organ donation/transplantation in each country and adoption of their 2020 proposed actions for organ/transplantation for member states, national registries with sharing of data with GODT, prevention of transplant commercialization and tourism. Additionally, adapting some aspects of proven successful models in LRCs will improve transplantation programmes in SSA.",signatures:"Ifeoma Ulasi, Chinwuba Ijoma, Ngozi Ifebunandu, Ejikeme Arodiwe, Uchenna Ijoma, Julius Okoye, Ugochi Onu, Chimezie Okwuonu, Sani Alhassan and Obinna Onodugo",downloadPdfUrl:"/chapter/pdf-download/74329",previewPdfUrl:"/chapter/pdf-preview/74329",authors:[{id:"326035",title:"Prof.",name:"Ifeoma",surname:"Ulasi",slug:"ifeoma-ulasi",fullName:"Ifeoma Ulasi"},{id:"326036",title:"Prof.",name:"Chinwuba",surname:"Ijoma",slug:"chinwuba-ijoma",fullName:"Chinwuba Ijoma"},{id:"326037",title:"Prof.",name:"Ejikeme",surname:"Arodiwe",slug:"ejikeme-arodiwe",fullName:"Ejikeme Arodiwe"},{id:"326038",title:"Dr.",name:"Chimezie",surname:"Okwuonu",slug:"chimezie-okwuonu",fullName:"Chimezie Okwuonu"},{id:"326039",title:"Dr.",name:"Julius",surname:"Okoye",slug:"julius-okoye",fullName:"Julius Okoye"},{id:"326040",title:"Dr.",name:"Obinna",surname:"Onodugo",slug:"obinna-onodugo",fullName:"Obinna Onodugo"},{id:"326249",title:"Prof.",name:"Sani",surname:"Alhassan",slug:"sani-alhassan",fullName:"Sani Alhassan"},{id:"336179",title:"Dr.",name:"Ugochi",surname:"Onu",slug:"ugochi-onu",fullName:"Ugochi Onu"},{id:"336182",title:"Prof.",name:"Ngozi",surname:"Ifebunandu",slug:"ngozi-ifebunandu",fullName:"Ngozi Ifebunandu"},{id:"336184",title:"Prof.",name:"Uchenna",surname:"Ijoma",slug:"uchenna-ijoma",fullName:"Uchenna Ijoma"}],corrections:null},{id:"73562",title:"Surgical Techniques of Multiorgan Procurement from a Deceased Donor",doi:"10.5772/intechopen.94156",slug:"surgical-techniques-of-multiorgan-procurement-from-a-deceased-donor",totalDownloads:521,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Solid organ transplantation is now the standard treatment for many types of diseases and using a standard surgical technique for organ procurement from the deceased donors is an important step in preventing complications after such complicated procedures. In most centers, retrieval of heart, lungs, liver, kidneys, small bowel, pancreas and other organs is done at the same time by different surgeons under supervision by a team leader who is most familiar with at least basic steps of surgical technique of procurement of all the solid organs. Each transplant surgeon, regardless of his or her sub-specialty, has to know how to prepare and dissect the delicate anatomical structures which are in common between the two adjacent organs for example portal vein (liver-pancreas), superior mesenteric vein (pancreas-small bowel), abdominal inferior vena cava (liver-kidneys), supra-diaphragmatic inferior vena cava (liver-heart) and pulmonary artery-veins (heart-lungs). This needs a multidisciplinary approach by the most experienced members of the transplant team to decrease the warm ischemic time of the organs without any harm to them by better coordination between all the surgeons. In this, chapter we briefly describe the multiorgan retrieval procedure in a deceased donor, and we hope that following these instructions results in better quality of the procured organs without jeopardizing their vital anatomical structures.",signatures:"Farzad Kakaei",downloadPdfUrl:"/chapter/pdf-download/73562",previewPdfUrl:"/chapter/pdf-preview/73562",authors:[{id:"26626",title:"Dr.",name:"Farzad",surname:"Kakaei",slug:"farzad-kakaei",fullName:"Farzad Kakaei"}],corrections:null},{id:"75579",title:"Thoracic Organ Procurement during Multi-Organ Retrieval",doi:"10.5772/intechopen.95793",slug:"thoracic-organ-procurement-during-multi-organ-retrieval",totalDownloads:324,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Procurement of thoracic organs can be divided into two major categories- donation after brain death (DBD) or donation after circulatory determination of death (DCDD). In this section we will focus primarily on DBD, which is the commoner of these two or at times referred to as standard procurement. DCDD is a relatively new and promising field that has helped ameliorate donor shortage, aided by the latest advances in medical technology. However, DBD continues to be the major avenue of organ donation. There are several different combinations of thoracic procurement surgeries: heart, double lung, single lung/ 2-single lungs, heart-lung en bloc for transplantation, Double Lung procurement for Bronchial arterial revascularization, Heart and Lung procurement in DCDD donors with the OCS, NRP or Lungs for EVLP.",signatures:"Suresh Keshavamurthy, Vipin Dulam, Eros Leotta, Mohammed A. Kashem and Yoshiya Toyoda",downloadPdfUrl:"/chapter/pdf-download/75579",previewPdfUrl:"/chapter/pdf-preview/75579",authors:[{id:"179835",title:"Dr.",name:"Yoshiya",surname:"Toyoda",slug:"yoshiya-toyoda",fullName:"Yoshiya Toyoda"},{id:"243073",title:"Dr.",name:"Suresh",surname:"Keshavamurthy",slug:"suresh-keshavamurthy",fullName:"Suresh Keshavamurthy"},{id:"244736",title:"Dr.",name:"Abul",surname:"Kashem",slug:"abul-kashem",fullName:"Abul Kashem"},{id:"327378",title:"Mr.",name:"Vipin",surname:"Dulam",slug:"vipin-dulam",fullName:"Vipin Dulam"},{id:"340389",title:"Dr.",name:"Eros",surname:"Leotta",slug:"eros-leotta",fullName:"Eros Leotta"}],corrections:null},{id:"73993",title:"Pathology of Intestinal Transplantation: Rejection and a Case of Tolerance",doi:"10.5772/intechopen.94361",slug:"pathology-of-intestinal-transplantation-rejection-and-a-case-of-tolerance",totalDownloads:344,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Small bowel transplants are less common than other organ transplants. Histological criteria for rejection of the transplanted small intestine were proposed at the 8th International Symposium on Small Intestinal Transplantation 2003-2004. The Banff Conference on Transplant Disease Pathology, an international conference on the rejection of small bowel transplants, was held in 2019, and unifying diagnostic criteria were discussed (https://banfffoundation.org/pittsburgh-2019/). These histological criteria are expected to be standardized in the near future. This review outlines new findings such as apoptosis and apoptotic-body phagocytic findings in the lamina propria and behavior of natural killer T (NKT) cells, in addition to previously known crypt Fas-related apoptosis in acute cellular rejection. Furthermore, we review the case of a recipient who has shown no rejection for 5 years after transplantation. In the transplanted small intestine of this patient, the lymphocytes were replaced by those of another male patient.",signatures:"Tatsuaki Tsuruyama",downloadPdfUrl:"/chapter/pdf-download/73993",previewPdfUrl:"/chapter/pdf-preview/73993",authors:[{id:"94907",title:"Prof.",name:"Tatsuaki",surname:"Tsuruyama",slug:"tatsuaki-tsuruyama",fullName:"Tatsuaki Tsuruyama"}],corrections:null},{id:"73970",title:"Regulatory T Cells in the Mosaic of Liver Transplantation Tolerance",doi:"10.5772/intechopen.94362",slug:"regulatory-t-cells-in-the-mosaic-of-liver-transplantation-tolerance",totalDownloads:271,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The success of transplantation depends on multiple factors, but the establishment of immune tolerant milieu is of critical importance. Hepatic environment consists of different cellular populations with prominent capacity to tolerate a huge range of antigens. Among them, regulatory T cells (Tregs) play an important role. They control the strength of immune reactions against non-self antigens and were shown to have an impact on the establishment of immune tolerance in the post-transplantation period. Furthermore, they impact a particular state after transplantation – operational tolerance. The abundant data show that Tregs might be manipulated, which suggests their further implementation as a treatment strategy. Tregs are also a very attractive target as a biomarker in the monitoring of post-transplantation period. Here, we review the particular role of Tregs among the broad spectrum of immune tolerance mechanisms of the liver in the light of the current directions of medical research.",signatures:"Velislava Terzieva, Yordanka Uzunova, Radosvet Gornev and Lubomir Spassov",downloadPdfUrl:"/chapter/pdf-download/73970",previewPdfUrl:"/chapter/pdf-preview/73970",authors:[{id:"326186",title:"Associate Prof.",name:"Velislava",surname:"Terzieva",slug:"velislava-terzieva",fullName:"Velislava Terzieva"}],corrections:null},{id:"74963",title:"Coupling and Deviating of Altruism-Voluntariness Relationship in Organ Transplantation",doi:"10.5772/intechopen.95895",slug:"coupling-and-deviating-of-altruism-voluntariness-relationship-in-organ-transplantation",totalDownloads:276,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Organ transplantation is an issue that concerns two people (donor and recipient) at the same time in terms of the right to life, which is the most basic human right. The direct utility arising from organ transplantation involves the patient to whom the organ is transplanted, and the indirect utility relates to the donor. Today, the decision to obtain an organ from a living donor is based on the idea of doing something good by those who sacrifice themselves for their relatives. The person who donates an organ treats their body as an instrument and uses their willpower on it. If the statement “I will care about the health of others” is accepted as a universal principle, it will be very important to establish a balance between the duty of caring for the health of others and protecting one’s own health. If we want to introduce a new approach to be adopted in the assessment of living donors in society, we must look at the real situation in terms of utility, altruism, and volunteering. This Chapter thus evaluates organ transplantation from living donors in terms of utility, altruism, and volunteering.",signatures:"Mesut Güvenbaş and Omur Sayligil",downloadPdfUrl:"/chapter/pdf-download/74963",previewPdfUrl:"/chapter/pdf-preview/74963",authors:[{id:"179771",title:"Prof.",name:"Omur",surname:"Sayligil",slug:"omur-sayligil",fullName:"Omur Sayligil"},{id:"328369",title:"MSc.",name:"Mesut",surname:"Güvenbaş",slug:"mesut-guvenbas",fullName:"Mesut Güvenbaş"}],corrections:null},{id:"73890",title:"Future Prospects of Organ Transplantation",doi:"10.5772/intechopen.94367",slug:"future-prospects-of-organ-transplantation",totalDownloads:389,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"The gap between organ demand and supply is an universal problem in organ and tissue transplantation therapy. The gap is growing in spite of efforts spent in medical, educational, social areas and mass media support. This reality has created the need for completely new therapeutic alternatives for the management of end-stage organ disease. The present research should continue in future aiming to discover systems and devices capable of totally replacing the traditional transplantation. On the other hand, a different progress in underway in transplantation. The indication for solid organ transplantation is to save life and promote quality of life. The new developing transplantations of composite tissue, uterus and face are performed with completely different indications. Facial defects caused by various insults cause serious functional and esthetic disorders, psychological and social problems. Facial transplant surgery is accomplished to overcome such problems. Uterus transplantation is emerging as an alternative to female infertility. Transplantation of composite tissue includes different organs. The main purpose of composite tissue transplantation is to restore reduced or completely lost functions and to increase the quality of life. Nerve regeneration must occur as a consequence of transplant to regain sensory and motor functions. It appears that the future of transplantation involves developments in two main streams; invention of completely new tools for solid organ transplantation and advances in the transplantation of different organs including uterus, face and composite tissue.",signatures:"Mehmet Nur Altinörs",downloadPdfUrl:"/chapter/pdf-download/73890",previewPdfUrl:"/chapter/pdf-preview/73890",authors:[{id:"326125",title:"Prof.",name:"Mehmet Nur",surname:"Altınörs",slug:"mehmet-nur-altinors",fullName:"Mehmet Nur Altınörs"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"6705",title:"Organ Donation and Transplantation",subtitle:"Current Status and Future Challenges",isOpenForSubmission:!1,hash:"e1ab81caf9179b0618c80dcd9bfd84a3",slug:"organ-donation-and-transplantation-current-status-and-future-challenges",bookSignature:"Georgios Tsoulfas",coverURL:"https://cdn.intechopen.com/books/images_new/6705.jpg",editedByType:"Edited by",editors:[{id:"57412",title:"Prof.",name:"Georgios",surname:"Tsoulfas",slug:"georgios-tsoulfas",fullName:"Georgios Tsoulfas"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6211",title:"Medical and Surgical Education",subtitle:"Past, Present and Future",isOpenForSubmission:!1,hash:"6c32a9763401f2d6e07b50f3e6451870",slug:"medical-and-surgical-education-past-present-and-future",bookSignature:"Georgios Tsoulfas",coverURL:"https://cdn.intechopen.com/books/images_new/6211.jpg",editedByType:"Edited by",editors:[{id:"57412",title:"Prof.",name:"Georgios",surname:"Tsoulfas",slug:"georgios-tsoulfas",fullName:"Georgios Tsoulfas"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7877",title:"Perioperative Care for Organ Transplant Recipient",subtitle:null,isOpenForSubmission:!1,hash:"f392542b05ddea5e08e4662dbc1dc8f7",slug:"perioperative-care-for-organ-transplant-recipient",bookSignature:"Alexander Vitin",coverURL:"https://cdn.intechopen.com/books/images_new/7877.jpg",editedByType:"Edited by",editors:[{id:"201176",title:"Associate Prof.",name:"Alexander",surname:"Vitin",slug:"alexander-vitin",fullName:"Alexander Vitin"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8267",title:"Basic Principles and Practice in Surgery",subtitle:null,isOpenForSubmission:!1,hash:"b7c5d304980da18193c583518f293f2f",slug:"basic-principles-and-practice-in-surgery",bookSignature:"Miana Gabriela Pop",coverURL:"https://cdn.intechopen.com/books/images_new/8267.jpg",editedByType:"Edited by",editors:[{id:"213382",title:"Dr.",name:"Miana Gabriela",surname:"Pop",slug:"miana-gabriela-pop",fullName:"Miana Gabriela Pop"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9790",title:"Surgical Management of Head and Neck Pathologies",subtitle:null,isOpenForSubmission:!1,hash:"8ae195fe1164fd55b69b775d596f1e8a",slug:"surgical-management-of-head-and-neck-pathologies",bookSignature:"Ho-Hyun (Brian) Sun",coverURL:"https://cdn.intechopen.com/books/images_new/9790.jpg",editedByType:"Edited by",editors:[{id:"184302",title:"Dr.",name:"H. 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1. Introduction
Contrast media is a substance that is used to enhance the differentiation of tissues within the body in medical imaging. They are administered either intravenously, intraarterially, orally or into body cavities, majority being administered intravenously. Over the past few years there has been an increase in the number of radiographic examinations that use contrast media for better lesion characterization, more so in CT and MRI examinations [1]. Although contrast media has become progressively safer over time, especially with the use of low osmolar contrast media (LOCM), anaphylactic reactions still do occur. It is estimated that 0.6% of iodinated and 0.12% of gadolinium contrast cause anaphylactic reactions [2, 3, 4]. Reactions to contrast media range from mild reactions to life threatening severe reactions. Most acute reactions occur within 1 hour of contrast media administration, with majority occurring within the first 20 minutes. Therefore, it is important to be aware of these reactions, to monitor the patient closely in this period and to manage the reactions when they do occur [5].
There are two main types of iodinated contrast comprising high osmolar (HOCM) or ionic contrast that dissociates in solution to form particles and low osmolar or non-ionic that does not dissociate in solution. Contrast media osmolality is determined by the number of particles formed in solution. Ionic contrast media dissociates into osmotically active ions in solution and therefore have a higher osmolality. Non-ionic agents do not dissociate to ions when dissolved in solution and hence have a lower osmolality. In recent years there has been a shift to using the LOCM because of associated fewer reactions therefore making contrast administration safer. Nevertheless, acute anaphylactic reactions can still occur unpredictably and therefore must be recognized and managed promptly. Some of the commonly used iodine-based contrast agents and their osmolality are listed in Table 1 above.
Types of contrast media
Contrast
Trade name
Ionic/Non-ionic
Iodine content
Osmolarity
Diatrizoate
Gastrografin
Ionic
300mg/ml
1550
Ioxaglate
Hexabrix
Ionic
320mg/ml
580
Ultravist
Iopromide
Non-ionic
300mg/ml
607
Optiray
Ioversal
Non-ionic
300mg/ml
651
Isovue 370
Iopamidol
Non-ionic
370mg/ml
796
Omnipaque 300
Iohexol
Non-ionic
300mg/ml
672
Ioxilan 350
Oxilan
Non-ionic
350mg/ml
695
Iotrol 300
Iotrolan
Non-ionic
300mg/ml
310
Visipaque 320
Iodixanol
Non-ionic
320mg/ml
290
Table 1.
Types of iodine based contrast media and osmolarity.
2. Gadolinium based contrast
Gadolinium based MRI contrast agents have been shown to be safe for intravenous administration, and actually a better safety profile than iodinated contrast for CT and other radiographic examinations. However acute reactions do occur and include urticaria, nausea and vomiting, and rarely anaphylaxis. In a study of 141,623 doses of MRI contrast administered Jae-woo et al. identified 0.079% immediate hypersensitivity reactions including urticaria, angioedema, bronchospasm and anaphylaxis and one fatality giving a mortality rate of 0.007% [6].
3. Presentation and management of contrast reactions
3.1 Clinical presentation
Reactions can be categorized as mild, moderate and severe as well as immediate and delayed. Mild reactions are usually self-limiting and require just supportive treatment, whereas moderate to severe reactions require prompt treatment. Delayed reactions such as abdominal pains, joint pains, fever and chills, diarrhea, headache, rashes and dizziness may be seen within two weeks from the date of contrast administration. Renal toxicity is also a commonly encountered side effect of contrast reactions manifesting as impaired renal function within two weeks of contrast administration.
Table 2 below shows the different types of reactions seen.
Severity
Reaction
Mild reactions
Urticaria
Hives
Nausea
Vomiting
Moderate reactions
Facial oedema
Severe vomiting
Bronchospasm
Laryngeal oedema
Severe reactions
Pulmonary oedema
Cardiac arrythmia
Cardiovascular collapse
Respiratory collapse
Table 2.
Classification of contrast media reactions.
Anaphylactic reaction usually occurs within one hour of contrast administration, with majority occurring within the first 20 minutes. This is a life-threatening reaction and manifests with hypotension, bronchospasm/laryngeal oedema and circulatory collapse. Patient evaluation algorithm is as outlined inFigure 1 above.
Figure 1.
Patient evaluation algorithm.
4. Anaphylactic reactions to contrast media
Although contrast side effects are infrequent, the knowledge of their presentation, their relationship with pre existing conditions and their management is required to ensure optimal patient care [2, 7]. Non ionic agents are iso-osmolar or low osmolar in nature and have fewer adverse effects [8, 9].
Majority of contrast reactions occur unpredictably and severe reactions may occur even when there has been a previous uneventful examination.
Risk factors that increase the likelihood of occurrence of adverse reactions [10, 11, 12] include:
Previous history of allergy like reaction to contrast media.
Allergy to food or other drugs.
History of asthma.
Renal insufficiency.
Cardiac disease e.g. Congestive cardiac failure, angina.
A detailed history should be obtained and pre medication administered prior to contrast use to reduce the risk of reaction occurrence.
Adverse reactions to contrast can be divided into organ specific and non organ specific or general reactions. They can also be classified into acute and delayed based on the timing after contrast administration.
Acute hypersensitivity reactions are those that develop within 1 hour of contrast administration and can classified into allergic-like and physiologic [13]. Allergic-like reactions are largely dose and concentration independent. They do not require prior sensitization or Ig-E and are thus called idiosyncratic /anaphylactoid reactions. They occur via direct mast cell stimulations or via activation of complement by immune complexes [14]. These are the most frequent type of adverse reactions and may have serious, occasionally fatal, complications.
Physiologic reactions are those that are dose and concentration dependent are thus called non idiosyncratic reactions. They are due to direct chemotoxic or osmotoxic effects of the contrast media [15].
These acute reactions can be further subclassified into into 3 categories based on severity-mild, moderate and severe [11]. Mild reactions are those that are self limiting. The mild allergic-like reactions include limited urticaria, pruritus, cutaneous edema, nasal congestion while the physiologic reactions include limited nausea and vomiting, transient flushing, headache, dizziness, anxiety and vasovagal reactions that resolve spontaneously [16]. Moderate reactions are those that are progressive and more pronounced and require medical management [17, 18]. The moderate allergic-like reactions include diffuse urticaria/pruritus, diffuse erythema with normal vital signs, facial edema, throat tightness, wheezing and bronchospasms. While the moderate physiological reactions include protracted vomiting, hypertensive urgency, vasovagal reactions that require treatment and respond to it [13]. Severe reactions are those that are potentially life threatening with impending death if not managed properly [2]. The severe allergic-like reactions include diffuse edema with dyspnea, diffuse erythema with hypotension, laryngeal edema with stridor, bronchospasms with hypoxia and anaphylactic shock. The severe physiologic reactions include vasovagal reactions resistant to treatment, convulsions, arrhythmia and hypertensive emergency [13]. The end result of severe allergic like and physiologic reactions is CPA which is a medical emergency and prompt and proper management using the BLS protocol and drugs including epinephrine, vasopressors, antihistamines and inhaled B-agonists is necessary to save lives.
Contrast induced acute kidney injury and nephropathy can also occur following contrast administration [19]. Risk factors include co morbidities like diabetes mellitus, dehydration, cardiac disease, hypertension and multiple iodinated contrast media doses in less than 24 hours. Baseline serum creatinine +/− glomerular filtration rate should be availed before injection of contrast media in at risk patients [13]. Contrast media administration in such patients can be done with caution by: reduced dose of contrast media, hydration and use of iso-osmolar agents.
5. Management of acute contrast media reactions
Management of acute contrast begins with discontinuation of injection if not completed [13, 20]. General principals of BLS and ACLS should apply in case of cardiorespiratory arrest.
Summary of the management of contrast reactions is as outlined inTable 3 below.
Reaction
Monitoring
Treatment
Anaphylactoid
Urticaria (skin rash)
Initial size with marking and follow
Mild-Usually none; if symptomatic consider diphenhydramine, 25–50 mg orally Moderate/Severe-monitor vitals and obtain IV access. Consider diphenhydramine, 25–50 mg orally intramuscularly/ intravenously; epinephrine (1:1,000), 0.1–0.3 mL subcutaneously/intramuscularly
Bronchospasm
Oxygen saturation, pulse, Blood pressure (BP)
In all forms of bronchospasms: preserve IV access, monitor vitals and oxygen saturation and give oxygen by mask 6-10 L/min Mild: Inhaled B-agonist- 2 puffs at 90mcg/puff and can be repeated up to 3 times. If response is not satisfactory, emergency response team should be contacted. Moderate Inhaled B-agonist- 2 puffs at 90mcg/puff and can be repeated up to 3 times Epinephrine (1:1000), 0.3 mL intramuscularly-this can be repeated every 5-15 minutes as needed up to 1 ml(1 mg)total; OR Epinephrine (1:10,000), 1 mL(0.1 mg) intravenously (slowly) if hypotensive; This can be repeated every few minutes as needed up to 10 ml(1 mg) total call the emergency medical team; call the emergency medical team Severe: Epinephrine (1:1000), 0.1–0.3 mL intramuscularly-this can be repeated every 5-15 minutes as needed up to 1 ml(1 mg)total; OR Epinephrine (1:10,000), 1 mL(0.1 mg) intravenously (slowly) if hypotensive; This can be repeated every few minutes as needed up to 10 ml(1 mg) total Call the emergency medical team and Inhaled B-agonist (may work synergistically). Call the emergency medical team
Facial or laryngeal edema
Oxygen saturation, pulse, BP
In all forms of laryngeal edema: preserve IV access, monitor vitals and oxygen saturation and give oxygen by mask 6-10 L/min Call the emergency medical team if severe Epinephrine (1:1000), 0.3 mL intramuscularly-this can be repeated every 5-15 minutes as needed up to 1 ml(1 mg)total; OR Epinephrine (1:10,000), 1 mL(0.1 mg) intravenously (slowly) if hypotensive; This can be repeated every few minutes as needed up to 10 ml(1 mg) total call the emergency medical team
Hypotension(systolic BP <90 mmHg) and tachycardia (>100 bpm)
Oxygen saturation, pulse, BP
Preserve IV access, Elevate legs 60°; oxygen, 6–10 L/min; rapid intravenous fluids(1 liter of 0.9% normal saline or lactated Ringer’s); epinephrine (1:10,000), 1 mL(0.1 mg) intravenously (slowly); This can be repeated every few minutes as needed up to 10 ml(1 mg) total OR Epinephrine (1:1000), 0.3 mL intramuscularly-this can be repeated every 5-15 minutes as needed up to 1 ml(1 mg)total call the emergency medical team
Hypotension(systolic BP <90 mmHg) and bradycardia (<60 bpm)
Oxygen saturation, pulse, BP
Elevate legs 60°; oxygen, 6–10 L/min; rapid intravenous fluids(1 liter of 0.9% normal saline or lactated Ringer’s) If mild, no further treatment is necessary If patient remains symptomatic despite the above measures: Atropine, 0.6–1 mg intravenously (slowly); repeat to total of 2–3 mg (0.04 mg/kg) if needed; call the emergency medical team
Cardiac arrhythmia
Oxygen saturation, pulse, BP, ECG
Follow ACLS protocols; call the emergency medical team
Hypertensive crisis (diastolic BP >120 mmHg; systolic BP >200 mmHg)
Oxygen saturation, pulse, BP, ECG
Nitroglycerine, 0.4 mg sublingually; can repeat every 5-10 minutes OR Labetalol intravenously 20 mg, administer slowly over 2 minutes. The dose can be doubled every 10 minutes. OR Lasix intravenously 20-40 mg,slowly over 2 minutes. Phentolamine, 5 mg intravenously for pheochromocytoma; Call the emergency medical team
Seizures
Oxygen saturation, pulse, BP, ECG
Observe and protect the patient Secure airway; oxygen, 6–10 L/min; Preserve IV access and give diazepam, 5 mg intramuscularly/intravenously OR midazolam, 0.5–1 mg intravenously OR phenytoin infusion, 15–18 mg/kg at 50 mg/min; call the emergency medical team
Hypoglycemia
Oxygen saturation, pulse, BP
If patient is able to swallow orally give half a cup of fruit juice or 15 g of glucose Is the patient is unable to swallow safely, obtain IV access and give 50% dextrose, 1 ampule-25gms over 2 minutes OR 100 ml/hr. of 5% dextrose. Is patient is unable to swallow and IV access is not available give intramuscular glucagon 1 mg.
Pulmonary edema
Oxygen saturation, pulse, BP, ECG
Preserve IV access, Secure airway; oxygen, 6–10 L/min; Elevate head of the bed furosemide, 20–40 mg intravenously (slowly over 2 minutes); morphine, 1–3 mg intravenously; call the emergency medical team
Table 3.
Management of contrast reactions.
6. Premedication of at risk patients
Premedication of patients who have a higher risk of acute allergic like reactions should be considered to reduce the chance of reaction occurrence [18]. For elective premedication oral prednisolone and diphenhydramine are used. For emergency premedication I.V methyl prednisolone sodium succinate or dexamethasone sodium sulfate. I.V diphenhydramine can be used instead of steroids in emergency cases [13].
7. Reaction rebound prevention
Intravenous corticosteroids play a role in preventing short term recurrence of an allergic like reactions. They may also be administered to patients having severe allergic like manifestations prior to transport to an emergency unit. They are however not useful in the acute treatment of any reaction.
7.1 Radiology department preparedness to manage anaphylactic reactions to contrast media
The hospital administration in liaison with the heads of the radiology department and the radiology contrast committee should set up and publish an institutional policy and procedure manual on contrast media administration.
The purpose of this manual is:
To ensure that administration of contrast media is done according to the protocols set up by the hospital and imaging department.
To ensure that in case of adverse reactions to contrast media, appropriate steps are taken to manage them.
To ensure that patients at risk of contrast media reactions or with prior history of such reactions receive appropriate premedication and are imaged using suitable protocols.
To ensure that patients due to receive intravenous contrast media have appropriate laboratory tests done and reviewed by the radiologist to determine their suitability for the procedure.
Guidelines for administration on intravenous contrast:
Administration of intravenous contrast should be done by a trained radiology technician / nurse under the supervision of the radiologist and these staff should be competent in recognizing and managing an adverse reaction if it occurs.
Standard operating procedures on the administration of intravenous contrast media should be set up and made available to the radiology clinical staff for reference when needed.
The Radiologist should review all the imaging requests that require administration of intravenous contrast, to determine the protocol to be used which will depend on the patient’s condition and clinical indication for the study.
The radiology technician and nurse attending to the patient must take a detailed history on the current clinical condition, current medications, history of allergy, asthma and prior adverse reactions to drugs and contrast media.
If the patient is found to have risk factors or contraindications to administration of contrast media, then the radiologist will determine the protocol to be followed and premedication to be administrated if required.
Protocols on the recognition and management of adverse reactions to contrast media should be set up and made available to all radiology clinical staff. These protocols ought to be illustrated in flow charts and placed in the various imaging sections in which intravenous contrast media is administered to facilitate proper management of these emergencies.
Close liaison between the radiology department, the emergency response team and intensive care unit must be present to ensure that the radiology department will get adequate support in case of an emergency.
7.2 Radiology department emergency trolley
All imaging sections in the radiology department must be equipped with the emergency equipment and medication required to monitor and manage a patient in cardiopulmonary arrest and more specifically a patient undergoing a severe reaction to contrast media.
Majority of the emergency equipment and medication are part of the standard crash cart/ emergency trolley; therefore, it is upon the administration of the radiology department to decide whether a dedicated contrast reaction kit is necessary. This will depend on the size of the imaging department, patient numbers and budget allocations.
The basic equipment required to monitor patients experiencing an adverse reaction to contrast media include:
Devices for hemodynamic Monitoring-Pulse and blood pressure monitors.
Devices for respiratory monitoring – Pulse oximeter.
Body temperature monitor – Thermometer or adhesive pads with thermoelectric transducer.
Blood glucose monitor.
Stethoscope.
Equipment and supplies for managing patients in an acute adverse reaction include:
Oxygen supply from a wall unit or oxygen cylinder.
Devices to supply the supplemental oxygen e.g. nasal cannula, simple face mask, face mask with oxygen reservoirs (non-rebreather mask). The latter is preferred as it is able to deliver a large dose of approximately 95–100% oxygen at a flow rate of 10-15 ml/min. Another device is a bag mask device which uses positive pressure ventilation with a face mask or advanced airway to administer a high concentration of oxygen to the patient. These devices must be available in adult and pediatric sizes.
Suction device used to clear the airway of secretions to enable the patient to breath. A patent airway is required for effective cardiopulmonary resuscitation in case of cardiopulmonary arrest in the case of severe contrast media reactions. The suction device may be wall mounted or mobile an I used in conjunction with suction tubing/ catheters.
Basic medication required in case of a contrast media reactions include:
Epinephrine
Emergency trolley / crash carts in hospital setting are usually equipped in 1 mg in 10 ml of epinephrine for intravenous administration (1:10000).
Epinephrine 1 mg in 1 ml vial is used for intramuscular injection.
Epinephrine autoinjectors in pediatric, and adult doses can also be used if available.
Oral and intravenous antihistamines.
Inhaled or nebulized B2 agonists.
Normal saline intravenous fluid in 500 ml and 1 liter bags/ bottles.
Atropine 1 mg in 10 ml for intravenous administration.
Additional medication and supplies include:
Emergency drugs – these include the standards emergency medications which are part of standard crash cart/ emergency trolley.
Supplies that form part of the standard emergency trolley like various sizes of intravenous cannulas, needles, syringes and intravenous giving sets.
Advanced cardiovascular life support equipment including:
Advanced airway adjuncts e.g. endotracheal tube.
Suction catheters.
Automated external defibrillator.
In view that cardiopulmonary arrest and adverse reactions to contrast media in the radiology department are rare, it is imperative that periodic stock checks are done to ensure the equipment and medications stocked for the management of these emergencies are within the recommended validity period.
7.3 Hospital emergency response team
When faced with a severe reaction to contrast media in which the patient’s condition warrants implementation of basic life support and advanced cardiac life support protocols, it is imperative that the hospital emergency response team be alerted to assist in initiation of these lifesaving protocols.
Modern radiology departments are fitted with an emergency bell that alerts the emergency response team to respond to an emergency in each imaging section. All radiology staff must be made aware of the location of these bells to activate them when needed.
In the event that such a system is not in place, the phone number of an internal/ external emergency response unit should be clearly posted in each imaging section.
7.4 Training
Despite the rare occurrence of contrast media reactions, they may carry substantial morbidity and mortality and thus require immediate intervention by the attending staff. These staff must therefore be equipped with the knowledge and skills to initiate effective cardiopulmonary resuscitation in order to manage these emergencies as they await the arrival of the emergency response team.
All clinical staff should receive life support training upon employment and thereafter attend at least three yearly refresher course as recommended by the American heart association.
Continuous medical education on contrast media reactions and their management should be held frequently to ensure these vital knowledge and skills are up to date.
Advanced radiology life support ™ is a course that uses concepts from basic life support and advanced cardiac life support to radiology clinical staff on recognizing and managing life threatening emergencies occurring in the imaging department.
This training covers:
Types of contrast media used in imaging.
Recognition of the signs and symptoms of contrast media reactions.
Risk factors of contrast induced nephropathy and approach to administration of contrast media in renal insufficiency.
Safety of Gadolinium based contrast agents and nephrogenic systemic fibrosis.
Airway management in emergencies.
Safe management of sedated patients in the imaging department.
Advanced radiology life support ™ has been successful in United states of America and Canada in training of radiologists, radiology technicians and nurses in the management of contrast media reactions and cardiopulmonary arrest in the radiology department. Accreditation is by the Mayo clinic of medicine and Science.
This training is available online in form interactive videos, therefore imaging departments should allocate a budget for purchase of this training for each of its clinical staff members.
\n',keywords:"anaphylaxis, iodinated contrast, bronchospasm, hypotension, diagnosis, treatment",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/74864.pdf",chapterXML:"https://mts.intechopen.com/source/xml/74864.xml",downloadPdfUrl:"/chapter/pdf-download/74864",previewPdfUrl:"/chapter/pdf-preview/74864",totalDownloads:194,totalViews:0,totalCrossrefCites:0,totalDimensionsCites:0,totalAltmetricsMentions:0,introChapter:null,impactScore:0,impactScorePercentile:41,impactScoreQuartile:2,hasAltmetrics:0,dateSubmitted:"December 7th 2020",dateReviewed:"December 28th 2020",datePrePublished:"January 19th 2021",datePublished:"March 9th 2022",dateFinished:"January 19th 2021",readingETA:"0",abstract:"Reactions to contrast agents are uncommon but range from mild urticaria to life threatening anaphylactic reactions. Majority of these reactions occur due to intravenous administration of iodinated contrast media. Acute reactions to MRI gadolinium-based contrast are much less common but they do occur and thus have to be managed. Usual presentations include urticaria, nausea, vomiting, angioedema, bronchospasm, laryngospasm and systemic hypotension. Majority of these reactions occur within the first twenty minutes after administration of contrast. Therefore, their recognition and prompt treatment are critical for good patient outcome. Attendant to this the radiology department must be adequately prepared to handle these emergencies as and when they do occur. This means an up to date emergency tray must be checked regularly before the start of the procedure, ensure there is epinephrine, antihistamines, beta-2-agonists metered dose inhalers, IV fluids, and ready supply of oxygen. Close collaboration of radiology staff with the hospital emergency response team is critical since severe reactions will need the intervention of this team.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/74864",risUrl:"/chapter/ris/74864",book:{id:"10324",slug:"recent-advances-in-asthma-research-and-treatments"},signatures:"Callen Kwamboka Onyambu, Angeline Anyona Aywak, Sarah Kemunto Osiemo and Timothy Musila Mutala",authors:[{id:"331476",title:"Dr.",name:"Callen",middleName:null,surname:"Kwamboka Onyambu",fullName:"Callen Kwamboka Onyambu",slug:"callen-kwamboka-onyambu",email:"callen.onyambu@uonbi.ac.ke",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"University of Nairobi",institutionURL:null,country:{name:"Kenya"}}},{id:"343549",title:"Dr.",name:"Angeline",middleName:null,surname:"Anyona Aywak",fullName:"Angeline Anyona Aywak",slug:"angeline-anyona-aywak",email:"angeline.aywak@uonbi.ac.ke",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"University of Nairobi",institutionURL:null,country:{name:"Kenya"}}},{id:"343550",title:"Dr.",name:"Sarah",middleName:null,surname:"Kemunto Osiemo",fullName:"Sarah Kemunto Osiemo",slug:"sarah-kemunto-osiemo",email:"skosiemo@gmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Kenyatta University",institutionURL:null,country:{name:"Kenya"}}},{id:"343551",title:"Dr.",name:"Timothy",middleName:null,surname:"Musila Mutala",fullName:"Timothy Musila Mutala",slug:"timothy-musila-mutala",email:"mutala@uonbi.ac.ke",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"University of Nairobi",institutionURL:null,country:{name:"Kenya"}}}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Gadolinium based contrast",level:"1"},{id:"sec_3",title:"3. Presentation and management of contrast reactions",level:"1"},{id:"sec_3_2",title:"3.1 Clinical presentation",level:"2"},{id:"sec_5",title:"4. Anaphylactic reactions to contrast media",level:"1"},{id:"sec_6",title:"5. Management of acute contrast media reactions",level:"1"},{id:"sec_7",title:"6. Premedication of at risk patients",level:"1"},{id:"sec_8",title:"7. Reaction rebound prevention",level:"1"},{id:"sec_8_2",title:"7.1 Radiology department preparedness to manage anaphylactic reactions to contrast media",level:"2"},{id:"sec_9_2",title:"7.2 Radiology department emergency trolley",level:"2"},{id:"sec_10_2",title:"7.3 Hospital emergency response team",level:"2"},{id:"sec_11_2",title:"7.4 Training",level:"2"}],chapterReferences:[{id:"B1",body:'Beckett KR, Moriarity AK, Langer JM. Safe use of contrast media: What the radiologist needs to know. Radiographics. 2015'},{id:"B2",body:'Singh J, Daftary A. Iodinated contrast media and their adverse reactions. Journal of Nuclear Medicine Technology. 2008'},{id:"B3",body:'Wang C.L., Cohan R.H., Ellis J.H., Caoili E.M., Wang G., Francis I.R. Frequency, outcome, and appropriateness of treatment of nonionic iodinated contrast media reactions. Am J Roentgenol. 2008;'},{id:"B4",body:'Gaeta TJ, Clark S, Pelletier AJ, Camargo CA. National study of US emergency department visits for acute allergic reactions, 1993 to 2004. Ann Allergy, Asthma Immunol. 2007;'},{id:"B5",body:'Osiem SK, Onyamb CK, Aywa AA. Knowledge and practices of cardiopulmonary arrest and anaphylactic reactions in the radiology department. South African J Radiol. 2020;'},{id:"B6",body:'Jung JW, Kang HR, Kim MH, Lee W, Min KU, Han MH, et al. Immediate hypersensitivity reaction to gadolinium-based MR contrast media. Radiology. 2012;'},{id:"B7",body:'Park HK, Kang MG, Yang MS, Jung JW, Cho SH, Kang HR. Epidemiology of drug-induced anaphylaxis in a tertiary hospital in Korea. Allergol Int. 2017;'},{id:"B8",body:'Katzberg RW, Haller C. Contrast-induced nephrotoxicity: Clinical landscape. Kidney Int. 2006;'},{id:"B9",body:'Katzberg RW. Urography into the 21st century: New contrast media, renal handling, imaging characteristics, and nephrotoxicity. Radiology. 1997'},{id:"B10",body:'Cohan RH, Ellis JH. Iodinated contrast material in uroradiology: Choice of agent and management of complications. Urol Clin North Am. 1997;'},{id:"B11",body:'Tublin ME, Murphy ME, Tessler FN. Current concepts in contrast media-induced nephropathy. American Journal of Roentgenology. 1998'},{id:"B12",body:'Mamoulakis C, Tsarouhas K, Fragkiadoulaki I, Heretis I, Wilks MF, Spandidos DA, et al. Contrast-induced nephropathy: Basic concepts, pathophysiological implications and prevention strategies. Pharmacology and Therapeutics. 2017'},{id:"B13",body:'ACR Committee on drugs and contrast Media. ACR Contrast Manual v10.3. American College of Radiology. 2018'},{id:"B14",body:'Almén T. The etiology of contrast medium reactions. Invest Radiol. 1994;'},{id:"B15",body:'Katzberg RW, Lamba R. Contrast-Induced Nephropathy after Intravenous Administration: Fact or Fiction? Radiologic Clinics of North America. 2009'},{id:"B16",body:'Böhm I, Heverhagen JT, Klose KJ. Classification of acute and delayed contrast media-induced reactions: Proposal of a three-step system. Contrast Media Mol Imaging. 2012;'},{id:"B17",body:'J.M. EM, S. MB, R. MB, R. VC, A. A-L. Clinical characteristics of adverse reaction to iodinated contrast media. Allergy Eur J Allergy Clin Immunol. 2013;'},{id:"B18",body:'Dispenza MC, Ditto AM. Adverse Reactions to Contrast Media. In: Drug Allergy Testing. 2018'},{id:"B19",body:'Hossain MA, Costanzo E, Cosentino J, Patel C, Qaisar H, Singh V, et al. Contrast-induced nephropathy: Pathophysiology, risk factors, and prevention. Saudi journal of kidney diseases and transplantation : an official publication of the Saudi Center for Organ Transplantation, Saudi Arabia. 2018'},{id:"B20",body:'Neumar RW, Shuster M, Callaway CW, Gent LM, Atkins DL, Bhanji F, et al. Part 1: Executive summary: 2015 American Heart Association guidelines update for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2015;'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Callen Kwamboka Onyambu",address:"callen.onyambu@uonbi.ac.ke",affiliation:'
Department of Diagnostic Imaging and Radiation Medicine, University of Nairobi, Kenya
Department of Diagnostic Imaging and Radiation Medicine, University of Nairobi, Kenya
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1. Introduction
Streptococcal skin and skin-structure infection (SSTI) is associated with significant morbidity all over the world and the impact is felt predominantly in resource-poor areas with inadequate personal hygiene and over-crowded living conditions. While exact numbers are difficult to estimate on account of the lack of systematic reporting, a literature search conducted by Sims and colleagues [1] reported an estimated prevalence of 18 million cases, with an incidence rate of around 1.78 million cases per year of invasive S. pyogenes (S. pyogenes) infection in 2005, and more than 140 million cases of impetigo globally each year as reported in the 2010 Global Burden of Disease study. Rising numbers of cases of infectious diseases of the skin is also seen in Western nations, probably driven by drug abuse and homelessness [2, 3]. Increased cases result in increased costs from emergency room visits and hospital care, hence outpatient parenteral antibiotic therapy (OPAT) has proven to be a valuable alternative to hospitalization [4], and when patients are chosen appropriately, OPAT results in very significant cost-savings without compromising outcomes [5]. Advances in pharmaceutical research has contributed to development of longer acting antibiotics that can be dosed once a day and in some cases once a week. There is ongoing research to determine the optimum duration of antibiotic therapy for these conditions.
Skin infections have been variously classified based on different criteria like depth of infection or the bacterial agents causing the infections or as primary infection in contrast to infection of pre-existing wounds or skin conditions. A very practical classification of patients hospitalized with skin infections (cellulitis versus abscess versus skin infections with additional complicating factors) has been described by Jenkins et al. [6]. The authors found in their study that cutaneous abscesses were primarily caused by Staphylococcus aureus and less often by the Streptococcus spp, in contrast with cellulitis which was caused primarily by β-hemolytic streptococci and less commonly by Staphylococcus spp. This differentiation is especially helpful when choosing the appropriate narrow spectrum antibiotic therapy for individual patients with these diagnoses. In contrast, “skin infections with additional complications” require more broad antibiotic coverage on account of mixed bacterial infection or infection with unusual organisms.
The clinical features of common streptococcal SSTIs and the antibiotics used in the management of these conditions will be further elaborated in this chapter.
2. Streptococcal pyoderma
Superficial skin infection has been described as impetigo or pyoderma. This is in contrast to more invasive diseases cellulitis and erysipelas. Impetigo (and the less precise term pyoderma) refers to superficial infection that begins in the form of a papule that progresses to a vesicle and pustule, ultimately forming crusted lesions (Figure 1). They resolve with hyper or hypopigmentation. These infections are caused either by Staphylococcus or Streptococcus, and one cannot clinically differentiate between the two causative organisms. They occur as a complication of underlying skin diseases like scabies [1] or contact dermatitis. The streptococci associated with these infections are most often group A (S. pyogenes). However other serotypes can also be isolated on cultures from these infections. Although considered benign, these infections could progress to more locally invasive cutaneous diseases (see below) and are associated with post-streptococcal complications like glomerulonephritis and acute rheumatic fever in resource limited populations (as reviewed in other chapters of this textbook).
Figure 1.
Impetigo secondary to infected contact dermatitis.
3. Treatment of impetigo
Antiseptic soaks and antibacterial creams are the mainstay of therapy for impetigo. A wide variety of topical antimicrobial agents are available including silver-based products, iodides, hydrogen peroxide, zinc, chlorhexidine and potassium permanganate. There is very little data in the literature comparing benefits of one product versus the other [7, 8]. Antibacterial creams: mupirocin, Na-fusidate and bacitracin are also available for use in localized superficial skin infections [9]. Drawbacks of topical therapy include development of resistance, risk of irritant or allergic dermatitis (sensitization), and if used in high concentrations, these could cause burn injuries.
4. Invasive streptococcal infections: erysipelas and cellulitis
When skin infection results in erythematous (red in color), edematous (raised above the surface) and well demarcated (sharp boundary between involved and uninvolved skin) areas of involvement, it is referred to as Erysipelas (Figure 2). Erysipelas is characterized by marked edema in the skin, sometimes severe enough to cause skin blisters. While it could be seen at any age, it is more common in the very young and in older individuals. Classically described as occurring on the face, it can be seen in other parts of the body including the trunk and extremities. It is commonly associated with systemic symptoms like fever, chills and body ache, and blood cultures could be positive. Erysipelas is most commonly caused by S. pyogenes but could also be caused by other streptococci and less commonly by S. aureus [10]. Superficial skin culture should not be obtained, and causative organism can be established if blood cultures return positive. The diagnosis is usually clinical and it responds well to antibiotic therapy. However, in patients with uncontrolled diabetes or other immunocompromising conditions, the infection can spread deeper and the patient could develop sepsis and shock. Recurrences—especially on the extremities—are common in patients with underlying chronic lymphedema [11].
Figure 2.
Erysipelas with sharply-defined edematous red skin lesions.
When streptococcal infection involves the skin as well as the subcutaneous tissue, it results in ill-defined areas of erythema that are rapidly spreading and this is called Cellulitis. The skin appears red with irregular spreading borders (Figure 3). The entry point for the infection is a break in the skin like a surgical wound or other skin trauma, underlying dermatoses like eczema and psoriasis or a fungal infection of the intertriginous areas like web spaces of the toes: “athlete’s foot” (Figure 4). The area of the skin involved is tender to touch, and cellulitis is associated with systemic symptoms like fever, chills and body ache. Sometimes infection spreads along a lymphatic channel rather than the entire skin and this is called streptococcal lymphangitis. (Figures 5 and 6) Blood cultures are positive in around 10% of cases [12, 13] which include patients with more severe disease, older patients, patients with underlying liver cirrhosis [12] and diabetes [13]. The yield of blood cultures is higher if cultures are obtained at the time when the patient is experiencing fever and chills. Cellulitis responds very quickly to appropriate antibiotic therapy. As with erysipelas, recurrences are common in those with underlying risk factors, and left untreated, the infection can spread to deeper tissues and result in sepsis and shock.
Figure 3.
Cellulitis with irregular and ill-defined borders.
Figure 4.
Fungal infection in the webspace of the toes, also called “athlete’s foot.”
Figure 5.
Lymphangitic streaking of the upper extremity.
Figure 6.
Lymphangitic streaking (double) of the lower extremity.
In some patients there is an overlap between erysipelas and cellulitis and the clinical differences are not so clear. Importantly, management of both conditions is similar.
5. Treatment of cellulitis and erysipelas
Mild localized infections are treated with oral antibiotics, while more extensive infections or infections with systemic symptoms are treated with parenteral (intravenous) antibiotic therapy [14]. Patients with signs of sepsis: fever or hypothermia, tachycardia and hypotension, and patients with underlying conditions like uncontrolled diabetes, liver cirrhosis, severe peripheral vascular disease or severe lymphedema and patients with immunocompromising conditions like HIV, or patients on chemotherapy should be admitted to the hospital for antibiotics as well as aggressive management of the underlying conditions. Penicillins and β-lactams are considered the antibiotics of choice for treatment of streptococcal cellulitis. The addition of a second antibiotic like trimethoprim/sulfamethoxazole (TMP/SMX) or clindamycin has been shown to provide no additional benefit [6, 15, 16, 17, 18]. Penicillins are available in the form of oral as well as intravenous preparations (Table 1). Extended spectrum penicillins: dicloxacillin, amoxicillin, ampicillin, oxacillin and nafcillin can be used if there is associated methicillin susceptible S. aureus (MSSA) infection. Cephalosporins are among the most commonly used β-lactams for the treatment of cellulitis. Different preparations are available both in the oral as well as the intravenous forms (Table 2). Physician preference and dosing convenience often define the choice of the antibiotic prescribed. Ceftaroline—one of the newest cephalosporins has excellent skin penetration and has activity against methicillin resistant S. aureus (MRSA) [19]. Patients who have an allergy to penicillin will require alternate agents. It should be noted here that there is increasing evidence in the literature indicating patients who claim penicillin allergy may not have a true allergy and are able to tolerate β-lactams [20, 21]. TMP-SMX [22], doxycycline, linezolid, clindamycin and fluoroquinolones (Table 3) all have excellent skin penetration and may be used as alternate oral agents in patients with allergies to penicillin and β-lactams. Severe cellulitis in patients who have a true allergy to both penicillin and β-lactams is treated with intravenous (IV) vancomycin. IV vancomycin requires close monitoring of levels to achieve optimized benefits while avoiding nephrotoxicity [23, 24], and often therapeutic levels are difficult to achieve in obese individuals [25]. Other alternatives to β-lactams are listed in Table 3. Daptomycin is a lipopeptide antibiotic that has excellent skin penetration. [26, 27]. It has the advantage of once- a- day dosing, making daptomycin a convenient agent for outpatient antibiotic therapy (OPAT). Other antibiotics with excellent skin penetration include linezolid [28, 29] and tigecycline [27, 30]. Both these antibiotics are dosed twice a day and hence less convenient for use as OPAT. Tigecycline is only available in the parenteral form and is recommended for patients hospitalized with severe infections. Linezolid is available in both parenteral as well as oral formulations. IV linezolid is used when a patient is hospitalized with severe cellulitis, and treatment can be completed with oral formulation once the patient improves. There are a number of newer agents approved for the management of SSTIs including long acting lipo-glycopeptide agents oritavancin and dalbavancin, extended-spectrum fluoroquinolone delafloxacin, and the new tetracycline derivative omadacycline [28, 29]. Important comments regarding the advantages as well as the potential side effects of these antibiotics are listed in Tables 3 and 4.
Non β-lactam antibiotics used for streptococcal skin infections.
Require dose adjustment in patients with kidney disease.
Name
Drug class
Dose
Comments
Dalbavancin
Lipo-glycopeptide
Intravenous: 1.5 g single dose
One dose IV provides 2 weeks of therapy
Oritavancin
Lipo-glycopeptide
Intravenous: 1.2 g single dose
One dose IV provides 2 weeks of therapy
Delafloxacin
Fluoroquinolone
Intravenous: 300 mg q 12 h Oral: 450 mg twice a day
Allows transition from IV to oral. Risks as with other FQ
Omadacycline
Tetracycline derivative
Intravenous: 200 mg X 1, then 100 mg daily Oral: 450 mg once a day for 2 days, then 300 mg once a day
Allows transition from IV to oral. Gastrointestinal side effects. Effective also against anaerobes
Tedizolid
Oxazolidinone
Intravenous: 200 mg, q 24 h Oral: 200 mg once a day
Allows transition from IV to oral. Risk for cytopenias, neuropathy
Table 4.
Newer antibiotics approved for treatment of skin infections.
Effective also against MSSA, MRSA.
6. Streptococcal infection of deeper tissues
When streptococcal infection spreads deep beyond the subcutaneous tissue, it can result in extensive necrosis (gangrene) of the overlying skin and inflammation and necrosis of underlying fascia (Streptococcal Necrotizing Fasciitis) and even muscle (Streptococcal Myositis). These infections are considered surgical emergencies.
Necrotizing Fasciitis (NF) is characterized by rapidly (within hours) spreading infection of the skin, subcutaneous tissue and fascia with associated symptoms of fever, prostration, hypotension and shock. It carries a high mortality [31]. It could start as a benign appearing skin wound that rapidly spreads both on the surface as well as into deeper tissues and the entire limb or body-part could be involved in a matter of a few hours. Skin changes include a rapid progression from mild erythema to a dusky appearance followed by ecchymosis, purpura, blisters and tissue necrosis—resulting in open wounds often discharging purulent or hemorrhagic fluid. (Figures 7 and 8) “Pain out of proportion to physical findings” is a characteristic sign of NF. In other words, there may be pain when palpating areas beyond the visible area of redness or in other cases even gentle palpation of involved area elicits excruciating pain. Some authorities divide NF into type I and type II. Type I is characterized by poly-microbial infection (involving both aerobic as well as anaerobic bacteria), while type II is characterized by mono-microbial infection of which group A streptococcus is the most commonly implicated organism [32]. Mortality was found to be lower in group A streptococcus—associated NF (type II) compared to type I: 10% versus 20% in one large study [31]. NF may also be seen in persons who inject drugs. In these cases, multiple skip lesions are seen (Figure 9) and infection is usually poly-microbial. In addition to the skin lesions, the patient usually has systemic symptoms of sepsis including high fever, tachycardia, hypotension and may progress to have multi-organ failure. Streptococcal pyrogenic exotoxins (Spe) A, B and C are responsible for causing stimulation of a severe inflammatory cascade resulting in injury not only at the area of infection (local necrosis) but also to distant sites (lungs, kidneys, liver, central nervous system). Blood cultures are universally positive, and imaging of involved body-part (CT scan or MRI) will demonstrate edema and/or gas in the soft tissue planes and other changes consistent with this diagnosis [33].
Figure 7.
Necrotizing fasciitis of the lower extremity.
Figure 8.
Clinical photograph showing erythema, peeling skin, dusky hue and areas of necrosis.
Figure 9.
Necrotic areas with skip lesions on leg of patient who is abusing self with injection drugs.
When infection spreads beyond the fascial planes into the underlying muscles it is called myositis. Streptococcal myositis is often a complication of the overlying skin infection. Sometimes a deep tissue hematoma caused by blunt trauma [34] could get inoculated by the organism in a patient with bacteremia. This too is an emergency and requires rapid surgical intervention to relieve the pressure created by the severe inflammation in the muscle planes (Figure 10). Patients will also have systemic symptoms and signs of sepsis as seen in NF. There is often overlap of these two conditions in many patients.
Figure 10.
Necrosis of skin, soft tissue and muscle with exposure of tendon.
7. Management of necrotizing fasciitis and streptococcal myositis
Patients need admission to the hospital often to the intensive care unit. They require management by a team of experts involving medical, surgical, infectious diseases and critical care specialties. They often present with septic shock and require pressors like epinephrine, norepinephrine and vasopressin to maintain adequate blood pressure in order to perfuse critical organs. Patients require broad spectrum antibiotic coverage, aggressive fluid resuscitation, as well as emergent aggressive debridement of the infected areas. Surgical removal of infected/necrotic tissue is essential in order to reduce bacterial burden and hence remove the source of toxins. Often patients require a second or even third visit to the operating room because of extensive tissue necrosis not amenable to removal in a single operation [14]. Operative tissue is sent for microbiology (cultures) to help determine the infectious agent and obtain an antibiotic sensitivity profile to help guide appropriate antibiotic choices. While awaiting the results of cultures, the antibiotics chosen should cover Gram-positive bacteria including Streptococcus and S. aureus, Gram-negative bacteria including drug-resistant bacteria like Pseudomonas, as well as anaerobic bacteria. Different combinations of antibiotics from Tables 1–3 can be used. IV vancomycin (or IV daptomycin) plus cefepime (or fluoroquinolone) plus metronidazole, or IV vancomycin (or IV daptomycin) plus meropenem (or imipenem), or IV daptomycin plus piperacillin- tazobactam are some potential options for empiric therapy. Linezolid could be used in place of vancomycin and daptomycin in the above combinations. Vancomycin, daptomycin and linezolid provide Gram-positive coverage, cefepime and fluoroquinolones provide Gram-negative coverage. While metronidazole provides only anaerobic coverage, imipenem, meropenem and piperacillin-tazobactam provide Gram-negative as well as anaerobic coverage. Clindamycin is added in the initial critical stages of the infection on account of its antitoxin effect [14, 33]. If linezolid is used, additional clindamycin is not required because linezolid itself also has an antitoxin effect [33]. When culture results become available, antibiotics should be deescalated to target the organisms identified. Intravenous immunoglobulins (IVIG) is used at some centers as part of management of NF, however large studies have not shown a statistically significant benefit compared to those patients who did not receive IVIG [14, 33].
8. Toxic shock syndrome (TSS)
TSS is associated with a dramatic widespread skin rash and severe systemic symptoms. This condition is not due to direct inoculation of the skin with Streptococcus, but rather it is secondary to exotoxin [35] released by Streptococcus infection at a distant site. Originally described in children with S. aureus infection, TSS is seen with Streptococcus and Clostridial infection in children as well as adults [36]. Patients present with widespread rash associated with fever, hypotension and multi-organ system involvement as a result of circulating streptococcal exotoxins A, B and C. The rash is described as sheets of erythema (Figure 11) involving the face, trunk as well as extremities, and it subsides with characteristic desquamation (Figure 12) when the patient recovers. A detailed examination is important to determine the source of infection: either retained foreign body like menstrual tampon or surgical sponge/dressing material, necrotizing infection in a deep space, post-operative wound infection or peritonitis. Rarely, streptococcal pharyngitis is the primary event. The circulating toxins (super-antigens) are responsible for injury to internal organs—lungs, kidneys, liver [35] and the disease can be fatal in 40 to 60% cases of streptococcal TSS especially when there is delay in the diagnosis and hence delayed initiation of appropriate antibiotics. Blood cultures may be positive, as are cultures from an identified focus of infection.
Figure 11.
Clinical photograph of sheet of erythema seen in acute phase of toxic shock syndrome.
Figure 12.
Toxic shock syndrome with desquamation in the recovery phase.
9. Management of TSS
As with other severe streptococcal infection, patients with TSS require admission to the hospital. If they are hypotensive or experience multi-organ failure, management is in the intensive care unit where patients are treated with aggressive fluid resuscitation, broad antibiotic therapy (choices similar to that as described for management of necrotizing fasciitis) and pressor support. Surgery may be required if a deep focus of infection is identified. Rarely patients do not respond to standard therapy and may require intravenous immunoglobulins (IVIG) [36].
10. Discussion on general principles of systemic antibiotic therapy
Streptococcal SSTIs respond very well to antibiotic therapy. A wide range of antibiotics with excellent skin penetration are now available as noted in Table 1–4. All antibiotics carry the potential for side effects like allergic reactions and gastrointestinal disturbances. There are some side effects that are unique to certain antibiotics and patients need to be monitored for these toxicities. For example: β-lactam antibiotics have the potential for hepatotoxicity, vancomycin is associated with nephrotoxicity, daptomycin can cause rhabdomyolysis and eosinophilic pneumonitis and clindamycin is one of the most common antibiotics associated with Clostridioides difficile (C. Diff) infection. In addition, inappropriate use of broad-spectrum antibiotics—and even prolonged use of narrow spectrum antibiotics—can result in collateral damage (destruction of protective normal bacterial flora of the skin and the gastrointestinal tract) and cause antibiotic-associated diarrhea and C. Diff infection [37, 38]. Indiscriminate use of broad-spectrum antibiotics has also contributed to the development of multidrug-resistant pathogens [39]. Therefore, judicious use of antibiotics is very important to reduce the risk of these complications. Streptococcal infections should be treated with narrow spectrum antibiotics like penicillin and β-lactams. When streptococcal cellulitis or erysipelas does not seem to be responding adequately within the first 2–3 days of β-lactam therapy, antibiotics with additional coverage against MRSA will need to be used.
11. Specific points regarding treatment of SSTIs
Mild infections should be treated with oral antibiotics.
Severe infections (severe local skin infection with systemic symptoms like fever, tachycardia, hypotension or leukocytosis and bacteremia, or more extensive skin infections even without systemic symptoms) will require parenteral therapy, with step-down to oral therapy as the patient improves [40]. Antibiotics like the floroquinolones: ciprofloxacin, levofloxacin, delafloxacin [41, 42], moxifloxacin [43], the oxazolidinones: linezolid, tedizolid and the new tetracycline: omadacycline [44] have excellent oral bioavailability and allow early conversion from intravenous to oral therapy.
In the most serious cases: sepsis, septic shock, necrotizing fasciitis, myositis, toxic shock syndrome: broad-spectrum antibiotics are required initially (most often with more than one antimicrobial agent) to cover Streptococcus, S. aureus including MRSA as well as gram-negative and anaerobic bacteria. “De-escalation” can be achieved once microbiology data (blood cultures, deep tissue and intraoperative cultures) are available to guide the final antibiotic choice targeting the bacteria identified.
Duration of antibiotics: This depends on the severity of the infection as well as the clinical response to therapy. Mild infections or even severe infections in an otherwise healthy host that respond rapidly to antibiotics could be treated for as short as 5 days [14, 45, 46]. More severe infections or infections with a delayed response to therapy may need longer courses like 7, 10 or 14 days, depending upon the clinical picture. Shorter courses may be possible with some of the newer antibiotics including single dose antibiotics like dalbavancin [47] and oritavancin [28]. Relapses are found to be more common in patients with shorter courses of therapy [45]. Patients with bacteremia are usually treated for 14 days.
Dose adjustments: Antibiotics are cleared by the liver or kidney and hence dosage needs to be reduced in patients with liver or kidney disease in order to avoid toxicity. Conversely, patients who are obese require a higher dose of the antibiotic to achieve therapeutic levels in the skin [25, 48].
Suppressive therapy is attempted for patients with multiple recurrences [45, 49, 50]. Oral penicillin twice daily showed a 70–80% reduction in episodes—but recurrences occurred after discontinuation of prophylaxis. Treatment of underlying factors like athlete’s foot, chronic lymphedema, peripheral vascular disease and uncontrolled diabetes is also very important in the prevention of recurrences [11, 44, 45, 51]
.
12. Conclusions
Streptococcal skin infections cause significant morbidity all over the world, and severe infections like necrotizing fasciitis and toxic shock syndrome can be fatal. There is a wide spectrum of manifestations of skin infections ranging from mild superficial disease to deep necrotic and life-threatening infections. Skin infection is one of the most common reasons for prescriptions of antibiotics in the community as well as in hospitalized patients. Some of the most commonly used antibiotics have excellent skin penetration and hence the armamentarium to treat skin infections is quite large. Over the last few years there have been multiple new antibiotics approved for the treatment of skin infections and these should be reserved for treatment of severe infections not responding to the common antibiotics and for infections with multi-drug-resistant organisms. A thorough understanding of the different types of skin infections, as well as a detailed knowledge of the different antibiotics are essential for the early diagnosis and selection of the most appropriate antibiotic for the management of simple as well as complex skin infections.
\n',keywords:"Streptococcus, Skin and Skin-Structure Infections (SSTI), Necrotizing Fasciitis (NF), Toxic Shock syndrome (TSS)",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/80546.pdf",chapterXML:"https://mts.intechopen.com/source/xml/80546.xml",downloadPdfUrl:"/chapter/pdf-download/80546",previewPdfUrl:"/chapter/pdf-preview/80546",totalDownloads:74,totalViews:0,totalCrossrefCites:0,dateSubmitted:"November 27th 2021",dateReviewed:"January 27th 2022",datePrePublished:"February 21st 2022",datePublished:null,dateFinished:"February 21st 2022",readingETA:"0",abstract:"Infections attributable to Streptococcus are protean. These range from mild skin and soft tissue infections to life-threatening conditions like meningitis, endocarditis and toxic shock syndrome. In addition, streptococcal infection can be associated with noninfectious sequelae like rheumatic fever and post-streptococcal glomerulonephritis. There is a wide range of Streptococcus spp. causing human infections and different classifications of these organisms have been described, the most quoted being the Lancefield classification based on cell-wall antigens. Streptococci can be studied based on their species: S. pyogenes, S. pneumoniae, S. anginosus etc. or by the Lancefield classification group A, B, C, D etc. or by the clinical syndromes associated with these bacteria. This chapter will describe clinical syndromes associated with streptococcal skin and soft tissue infections ranging from mild: cellulitis and lymphangitis which can be treated in the out-patient setting, to more aggressive manifestations that require hospitalization (sepsis and toxic shock syndrome) and even surgery (necrotizing fasciitis, myositis and gangrene), It will also provide clues to clinical diagnosis as well as suggest recommendations for optimized management of these conditions.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/80546",risUrl:"/chapter/ris/80546",signatures:"Alwyn Rapose",book:{id:"10828",type:"book",title:"Streptococcal Infections",subtitle:null,fullTitle:"Streptococcal Infections",slug:null,publishedDate:null,bookSignature:"Dr. Hassan Hemeg",coverURL:"https://cdn.intechopen.com/books/images_new/10828.jpg",licenceType:"CC BY 3.0",editedByType:null,isbn:"978-1-80355-316-0",printIsbn:"978-1-80355-315-3",pdfIsbn:"978-1-80355-317-7",isAvailableForWebshopOrdering:!0,editors:[{id:"187330",title:"Dr.",name:"Hassan",middleName:null,surname:"Hemeg",slug:"hassan-hemeg",fullName:"Hassan Hemeg"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:null,sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Streptococcal pyoderma",level:"1"},{id:"sec_3",title:"3. Treatment of impetigo",level:"1"},{id:"sec_4",title:"4. Invasive streptococcal infections: erysipelas and cellulitis",level:"1"},{id:"sec_5",title:"5. Treatment of cellulitis and erysipelas",level:"1"},{id:"sec_6",title:"6. Streptococcal infection of deeper tissues",level:"1"},{id:"sec_7",title:"7. Management of necrotizing fasciitis and streptococcal myositis",level:"1"},{id:"sec_8",title:"8. Toxic shock syndrome (TSS)",level:"1"},{id:"sec_9",title:"9. Management of TSS",level:"1"},{id:"sec_10",title:"10. Discussion on general principles of systemic antibiotic therapy",level:"1"},{id:"sec_11",title:"11. Specific points regarding treatment of SSTIs",level:"1"},{id:"sec_12",title:"12. Conclusions",level:"1"}],chapterReferences:[{id:"B1",body:'Sims Sanyahumbi A, Colquhoun S, Wyber R, et al. Global disease burden of Group A Streptococcus. In: Ferretti JJ, Stevens DL, Fischetti VA, editors. Streptococcus pyogenes: Basic Biology to Clinical Manifestations. Oklahoma City (OK), USA: University of Oklahoma Health Sciences Center; 2016'},{id:"B2",body:'https://wwwnc.cdc.gov/eid/article/15/9/08-1228_article [Accessed: November 15, 2021]'},{id:"B3",body:'https://wwwnc.cdc.gov/eid/article/27/2/20-1945_article [Accessed: November 15, 2021]'},{id:"B4",body:'Norris AH, Shrestha NK, Allison GM, et al. 2018 Infectious Diseases Society of America Clinical Practice Guideline for the Management of Outpatient Parenteral Antimicrobial Therapy. Clinical Infectious Diseases. 2019;68(1):e1-e35'},{id:"B5",body:'Keyloun KR, Weber DJ, Gardstein BM, et al. Economic burden of hospital admissions for patients with acute bacterial skin and skin structure infections in the United States. Hospital Practice. 2018;46(5):278-286'},{id:"B6",body:'Jenkins TC, Sabel AL, Sarcone EE, et al. Skin and soft-tissue infections requiring hospitalization at an academic medical center: Opportunities for antimicrobial stewardship. Clinical Infectious Diseases. 2010;51(8):895-903'},{id:"B7",body:'Dumville JC, Lipsky BA, Hoey C, et al. Topical antimicrobial agents for treating foot ulcers in people with diabetes. Cochrane Database of Systematic Reviews. 2017;6(6):CD011038'},{id:"B8",body:'Delgado-Enciso I, Madrigal-Perez VM, Lara-Esqueda A, et al. Topical 5% potassium permanganate solution accelerates the healing process in chronic diabetic foot ulcers. Biomedical Reports. 2018;8(2):156-159'},{id:"B9",body:'Williamson DA, Carter GP, Howden BP. Current and emerging topical antibacterials and antiseptics: Agents, action, and resistance patterns. Clinical Microbiology Reviews. 2017;30(3):827-860'},{id:"B10",body:'Eriksson B, Jorup-Ronstrom C, Karkkonen K, et al. Erysipelas: Clinical and bacteriologic spectrum and serological aspects. Clinical Infectious Diseases. 1996;23(5):1091-1098'},{id:"B11",body:'Inghammar M, Rasmussen M, Linder A. Recurrent erysipelas-risk factors and clinical presentation. BMC Infectious Diseases. 2014;14(1):270-275'},{id:"B12",body:'Lee CY, Kunin CM, Chang C, et al. Development of a prediction model for bacteremia in hospitalized adults with cellulitis to aid in the efficient use of blood cultures: A retrospective cohort study. BMC Infectious Diseases. 2016;16(1):581'},{id:"B13",body:'Lasa JS, Fernández Recalde ML, Finn BC, et al. Bacteremia in patients hospitalized with cellulitis. Medicina (B Aires). 2012;72(4):298-304'},{id:"B14",body:'Stevens DL, Bisno AL, Chambers HF, et al. Infectious Diseases Society of America Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America. Clinical Infectious Diseases. 2014;59:e10-e52'},{id:"B15",body:'Madaras-Kelly KJ, Remington RE, Oliphant CM, et al. Efficacy of oral beta-lactam versus non-beta-lactam treatment of uncomplicated cellulitis. The American Journal of Medicine. 2008;121(5):419-425'},{id:"B16",body:'Jeng A, Beheshti M, Li J, et al. The role of beta-hemolytic streptococci in causing diffuse, nonculturable cellulitis: A prospective investigation. Medicine (Baltimore). 2010;89(4):217-226'},{id:"B17",body:'Pallin DJ, Binder WD, Allen MB, et al. Clinical trial: Comparative effectiveness of cephalexin plus trimethoprim-sulfamethoxazole versus cephalexin alone for treatment of uncomplicated cellulitis: A randomized controlled trial. Clinical Infectious Diseases. 2013;56(12):1754-1762'},{id:"B18",body:'Brindle R, Williams OM, Davies P, et al. Adjunctive clindamycin for cellulitis: A clinical trial comparing flucloxacillin with or without clindamycin for the treatment of limb cellulitis. BMJ Open. 2017;7(3):e013260'},{id:"B19",body:'Santos PD, Davis A, Jandourek A, et al. Ceftaroline fosamil and treatment of acute bacterial skin and skin structure infections: CAPTURE study experience. Chemotherapy. 2013;25(6):341-346'},{id:"B20",body:'Blumenthal KG, Peter JG, Trubiano JA, et al. Antibiotic allergy. Lancet. 2019;393(10167):183-198'},{id:"B21",body:'Staicu ML, Vyles D, Shenoy ES, et al. Penicillin allergy delabeling: A multidisciplinary opportunity. The Journal of Allergy and Clinical Immunology. 2020;8(9):2858-2868'},{id:"B22",body:'Bowen AC, Carapetis JR, Currie BJ, et al. Sulfamethoxazole-Trimethoprim (Cotrimoxazole) for skin and soft tissue infections including impetigo, cellulitis, and abscess. Open Forum Infectious Diseases. 2017;4(4):ofx232'},{id:"B23",body:'Rybak MJ, Le J, Lodise TP, et al. Therapeutic monitoring of vancomycin for serious methicillin-resistant Staphylococcus aureus infections: A revised consensus guideline and review by the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists. American Journal of Health-System Pharmacy. 2020;77(11):835-864'},{id:"B24",body:'Jorgensen SCJ, Murray KP, Lagnf AM, et al. A multicenter evaluation of vancomycin-associated acute kidney injury in hospitalized patients with acute bacterial skin and skin structure infections. Infectious Disease and Therapy. 2020;9(1):89-106'},{id:"B25",body:'Smit C, Wasmann RE, Goulooze SC, et al. Population pharmacokinetics of vancomycin in obesity: Finding the optimal dose for (morbidly) obese individuals. British Journal of Clinical Pharmacology. 2020;86(2):303-317'},{id:"B26",body:'Sauermann R, Rothenburger M, Graninger W, et al. Daptomycin: A review 4 years after first approval. Pharmacology. 2008;81(2):79-91'},{id:"B27",body:'Eckmann C, Dryden M. Treatment of complicated skin and soft-tissue infections caused by resistant bacteria: Value of linezolid, tigecycline, daptomycin and vancomycin. European Journal of Medical Research. 2010;15(12):554-563'},{id:"B28",body:'Golan Y. Current treatment options for acute skin and skin-structure infections. Clinical Infectious Diseases. 2019;68(Suppl. 3):S206-S212'},{id:"B29",body:'Crotty MP, Krekel T, Burnham CA, et al. New gram-positive agents: The next generation of oxazolidinones and lipoglycopeptides. Journal of Clinical Microbiology. 2016;54(9):2225-2232'},{id:"B30",body:'Grolman DC. Therapeutic applications of tigecycline in the management of complicated skin and skin structure infections. International Journal of Infectious Diseases. 2007;11(Suppl. 1):S7-S15'},{id:"B31",body:'Bruun T, Rath E, Madsen MB, et al. Risk factors and predictors of mortality in streptococcal necrotizing soft-tissue infections: A multicenter prospective study. INFECT Study Group. Clinical Infectious Diseases. 2021;72(2):293-300'},{id:"B32",body:'Kiat HJ, En Natalie YH, Fatimah LJ. Necrotizing fasciitis: How reliable are the cutaneous signs? Journal of Emergencies, Trauma and Shock. 2017;10(4):205-210'},{id:"B33",body:'Bonne SL, Kadri SS. Evaluation and management of necrotizing soft tissue infections. Infectious Disease Clinics of North America. 2017;31(3):497-511'},{id:"B34",body:'Nuwayhid ZB, Aronoff DM, Mulla ZD. Blunt trauma as a risk factor for group A streptococcal necrotizing fasciitis. Annals of Epidemiology. 2007;17(11):878-881'},{id:"B35",body:'Emgård J, Bergsten H, McCormick JK, et al. MAIT cells are major contributors to the cytokine response in group A streptococcal toxic shock syndrome. Proceedings of the National Academy of Sciences of the United States of America. 2019;116(51):25923-25931'},{id:"B36",body:'Rapose A. Toxic Shock Syndrome. In: Conn’s Current Therapy. Philadelphia (PA), USA: Elsevier Health Sciences; 2021. pp. 666-668'},{id:"B37",body:'Brown KA, Khanafer N, Daneman N, et al. Meta-analysis of antibiotics and the risk of community-associated Clostridium difficile infection. Antimicrobial Agents and Chemotherapy. 2013;57(5):2326-2332'},{id:"B38",body:'Webb BJ, Subramanian A, Lopansri B, et al. Antibiotic exposure and risk for hospital-associated Clostridioides difficile infection. Antimicrobial Agents and Chemotherapy. 2020;64(4):e02169-e02119'},{id:"B39",body:'Moghnieh R, Estaitieh N, Mugharbil A, et al. Third generation cephalosporin resistant Enterobacteriaceae and multidrug resistant gram-negative bacteria causing bacteremia in febrile neutropenia adult cancer patients in Lebanon, broad spectrum antibiotics use as a major risk factor, and correlation with poor prognosis. Frontiers in Cellular and Infection Microbiology. 2015;12(5):11'},{id:"B40",body:'Nathwani D, Dryden M, Garau J. Early clinical assessment of response to treatment of skin and soft-tissue infections: How can it help clinicians? Perspectives from Europe. International Journal of Antimicrobial Agents. 2016;48(2):127-136'},{id:"B41",body:'O\'Riordan W, McManus A, Teras J, et al. A comparison of the efficacy and safety of intravenous followed by oral delafloxacin with vancomycin plus aztreonam for the treatment of acute bacterial skin and skin structure infections: A phase 3, Multinational, Double-Blind, Randomized Study. PROCEED Study Group. Clinical Infectious Diseases. 2018;67(5):657-666'},{id:"B42",body:'Kingsley J, Mehra P, Lawrence LE, et al. A randomized, double-blind, Phase 2 study to evaluate subjective and objective outcomes in patients with acute bacterial skin and skin structure infections treated with delafloxacin, linezolid or vancomycin. The Journal of Antimicrobial Chemotherapy. 2016;71(3):821-829'},{id:"B43",body:'Gyssens IC, Dryden M, Kujath P, et al. A randomized trial of the efficacy and safety of sequential intravenous/oral moxifloxacin monotherapy versus intravenous piperacillin/tazobactam followed by oral amoxicillin/clavulanate for complicated skin and skin structure infections. The Journal of Antimicrobial Chemotherapy. 2011;66(11):2632-2642'},{id:"B44",body:'Abrahamian FM, Sakoulas G, Tzanis E, et al. Omadacycline for acute bacterial skin and skin structure infections. Clinical Infectious Diseases. 2019;69(Suppl. 1):S23-S32'},{id:"B45",body:'Cranendonk DR, Opmeer BC, van Agtmael MA, et al. Antibiotic treatment for 6 days versus 12 days in patients with severe cellulitis: A multicentre randomized, double-blind, placebo-controlled, non-inferiority trial. Clinical Microbiology and Infection. 2020;26(5):606-612'},{id:"B46",body:'Morris AD. Cellulitis and erysipelas. BMJ Clinical Evidence. 2008;2008:1708'},{id:"B47",body:'Bennett JW, Lewis JS, Ellis MW. Dalbavancin in the treatment of complicated skin and soft-tissue infections: A review. Therapeutics and Clinical Risk Management. 2008;4(1):31-40'},{id:"B48",body:'Grupper M, Nicolau DP. Obesity and skin and soft tissue infections: How to optimize antimicrobial usage for prevention and treatment? Current Opinion in Infectious Diseases. 2017;30(2):180-191'},{id:"B49",body:'Thomas KS, Crook AM, Nunn AJ, et al. Penicillin to prevent recurrent leg cellulitis. The New England Journal of Medicine. 2013;368(18):1695-1703'},{id:"B50",body:'Dalal A, Eskin-Schwartz M, Mimouni D, et al. Interventions for the prevention of recurrent erysipelas and cellulitis. Cochrane Database of Systematic Reviews. 2017;6(6):CD009758'},{id:"B51",body:'Wilcox M, Yan JL, Gonzalez PL, et al. Impact of underlying comorbidities on outcomes of patients treated with Ceftaroline Fosamil for complicated skin and soft tissue infections: Pooled results from three phase III Randomized Clinical Trials. Infectious Disease and Therapy. 2022;11(1):217-230'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Alwyn Rapose",address:"Alwyn.rapose@reliantmedicalgroup.org",affiliation:'
University of Massachusetts Medical School, Reliant Medical Group, Worcester, Massachusetts, USA
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Assoc Prof Ashwath supervises post graduate students on a range of topics, including phytoremediation, phytocapping and mine site restoration. His contribution to research at CQU has won him the Vice Chancellor’s Award for research. He has authored/co-authored over 200 publications and serves in the editorial committees of ~10 journals.",institutionString:null,institution:{name:"Central Queensland University",country:{name:"Australia"}}},{id:"131328",title:"Prof.",name:"Abdennasser",middleName:null,surname:"Chebira",slug:"abdennasser-chebira",fullName:"Abdennasser Chebira",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/131328/images/system/131328.jpg",biography:"Dr. Abdennasser Chebira received his Ph.D. degree in Electrical Engineering and Computer Sciences from PARIS XI University, Orsay, France, in 1994. Since September 1994 he works as Professor Assistant at Sénart Institute of Technology of PARIS XII – Val de Marne University. He is a staff researcher at Images, Signal and Intelligent Systems Laboratory (LISSI / EA 3956) of this University. 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It is a cofactor for enzymes involved in regulating photosynthesis, hormone biosynthesis, and regenerating other antioxidants; which also regulates cell division and growth, is involved in signal transduction, and has roles in several physiological processes, such as immune stimulation, synthesis of collagen, hormones, neurotransmitters, and iron absorption, has also roles in detoxifying the body of heavy metals. Severe deficiency of vitamin C causes scurvy, whereas limited vitamin C intake causes symptoms, such as increased susceptibility to infections, loosening of teeth, dryness of the mouth and eyes, loss of hair, dry itchy skin, fatigue, and insomnia. In contrast, vitamin C can also act as a prooxidant, especially in the presence of transition metals, such as iron and copper, starting different hazardous radical reactions. Vitamin C can both act as a strong, efficient, and cheap antioxidant agent and, at the same time, behave as a radical promoter. Further investigations are needed to illuminate the dual roles of vitamin C",book:{id:"5940",slug:"vitamin-c",title:"Vitamin C",fullTitle:"Vitamin C"},signatures:"Fadime Eryılmaz Pehlivan",authors:[{id:"200567",title:"Dr.",name:"Fadime",middleName:null,surname:"Eryılmaz Pehlivan",slug:"fadime-eryilmaz-pehlivan",fullName:"Fadime Eryılmaz Pehlivan"}]},{id:"56440",doi:"10.5772/intechopen.70162",title:"Vitamin C: Sources, Functions, Sensing and Analysis",slug:"vitamin-c-sources-functions-sensing-and-analysis",totalDownloads:6438,totalCrossrefCites:15,totalDimensionsCites:28,abstract:"Vitamin C is a water-soluble compound found in living organisms. It is an essential nutrient for various metabolism in our body and also serves as a reagent for the preparation of many materials in the pharmaceutical and food industry. In this perspective, this chapter can develop interest and curiosity among all practicing scientists and technologists by expounding the details of its sources, chemistry, multifunctional properties and applications.",book:{id:"5940",slug:"vitamin-c",title:"Vitamin C",fullTitle:"Vitamin C"},signatures:"Sudha J. Devaki and Reshma Lali Raveendran",authors:[{id:"187911",title:"Associate Prof.",name:"Sudha",middleName:null,surname:"J Devaki",slug:"sudha-j-devaki",fullName:"Sudha J Devaki"},{id:"204937",title:"Mrs.",name:"Reshma",middleName:null,surname:"Laly Ravindran",slug:"reshma-laly-ravindran",fullName:"Reshma Laly Ravindran"}]},{id:"50921",doi:"10.5772/63712",title:"Menaquinones, Bacteria, and Foods: Vitamin K2 in the Diet",slug:"menaquinones-bacteria-and-foods-vitamin-k2-in-the-diet",totalDownloads:3328,totalCrossrefCites:10,totalDimensionsCites:21,abstract:"Vitamin K2 is a collection of isoprenologues that mostly originate from bacterial synthesis, also called menaquinones (MKs). Multiple bacterial species used as starter cultures for food fermentation are known to synthesize MK. Therefore, fermented food is the best source of vitamin K2. In the Western diet, dairy products are one of the best known and most commonly consumed group of fermented products.",book:{id:"5169",slug:"vitamin-k2-vital-for-health-and-wellbeing",title:"Vitamin K2",fullTitle:"Vitamin K2 - Vital for Health and Wellbeing"},signatures:"Barbara Walther and Magali Chollet",authors:[{id:"184784",title:"Dr.",name:"Barbara",middleName:null,surname:"Walther",slug:"barbara-walther",fullName:"Barbara Walther"},{id:"188194",title:"Mrs.",name:"Magali",middleName:null,surname:"Chollet",slug:"magali-chollet",fullName:"Magali Chollet"}]},{id:"66098",doi:"10.5772/intechopen.84445",title:"Golden Rice: To Combat Vitamin A Deficiency for Public Health",slug:"golden-rice-to-combat-vitamin-a-deficiency-for-public-health",totalDownloads:3386,totalCrossrefCites:12,totalDimensionsCites:17,abstract:"Vitamin A deficiency (VAD) has been recognised as a significant public health problem continuously for more than 30 years, despite current interventions. The problem is particularly severe in populations where rice is the staple food and diversity of diet is limited, as white rice contains no micronutrients. Golden Rice is a public-sector product designed as an additional intervention for VAD. There will be no charge for the nutritional trait, which has been donated by its inventors for use in public-sector rice varieties to assist the resource poor, and no limitations on what small farmers can do with the crop—saving and replanting seed, selling seed and selling grain are all possible. Because Golden Rice had to be created by introducing two new genes—one from maize and the other from a very commonly ingested soil bacterium—it has taken a long time to get from the laboratory to the field. Now it has been formally registered as safe as food, feed, or in processed form by four industrialised counties, and applications are pending in developing countries. The data are summarised here, and criticisms addressed, for a public health professional audience: is it needed, will it work, is it safe and is it economic? Adoption of Golden Rice, the next step after in-country registration, requires strategic and tactical cooperation across professions, non-governmental organisations (NGOs) and government departments often not used to working together. Public health professionals need to play a prominent role.",book:{id:"7978",slug:"vitamin-a",title:"Vitamin A",fullTitle:"Vitamin A"},signatures:"Adrian Dubock",authors:[{id:"273220",title:"Ph.D.",name:"Adrian",middleName:null,surname:"Dubock",slug:"adrian-dubock",fullName:"Adrian Dubock"}]},{id:"62836",doi:"10.5772/intechopen.79350",title:"The Role of Thiamine in Plants and Current Perspectives in Crop Improvement",slug:"the-role-of-thiamine-in-plants-and-current-perspectives-in-crop-improvement",totalDownloads:1566,totalCrossrefCites:7,totalDimensionsCites:11,abstract:"Current research is focusing on selecting potential genes that can alleviate stress and produce disease-tolerant crop variety. The novel paradigm is to investigate the potential of thiamine as a crop protection molecule in plants. Thiamine or vitamin B1 is important for primary metabolism for all living organisms. The active form, thiamine pyrophosphate (TPP), is a cofactor for the enzymes involved in the synthesis of amino acids, tricarboxylic acid cycle and pentose phosphate pathway. Recently, thiamine is shown to have a role in the processes underlying protection of plants against biotic and abiotic stresses. The aim of this chapter is to review the role of thiamine in plant growth and disease protection and also to highlight that TPP and its intermediates are involved in management of stress. The perspectives on its potential for manipulating the biosynthesis pathway in crop improvement will also be discussed.",book:{id:"6709",slug:"b-group-vitamins-current-uses-and-perspectives",title:"B Group Vitamins",fullTitle:"B Group Vitamins - Current Uses and Perspectives"},signatures:"Atiqah Subki, Aisamuddin Ardi Zainal Abidin and Zetty Norhana\nBalia Yusof",authors:[{id:"240031",title:"Dr.",name:"Zetty-Norhana Balia",middleName:null,surname:"Yusof",slug:"zetty-norhana-balia-yusof",fullName:"Zetty-Norhana Balia Yusof"},{id:"261167",title:"Mr.",name:"Aisamuddin Ardi",middleName:null,surname:"Zainal Abidin",slug:"aisamuddin-ardi-zainal-abidin",fullName:"Aisamuddin Ardi Zainal Abidin"},{id:"261169",title:"Ms.",name:"Atiqah",middleName:null,surname:"Subki",slug:"atiqah-subki",fullName:"Atiqah Subki"}]}],mostDownloadedChaptersLast30Days:[{id:"56440",title:"Vitamin C: Sources, Functions, Sensing and Analysis",slug:"vitamin-c-sources-functions-sensing-and-analysis",totalDownloads:6429,totalCrossrefCites:15,totalDimensionsCites:28,abstract:"Vitamin C is a water-soluble compound found in living organisms. It is an essential nutrient for various metabolism in our body and also serves as a reagent for the preparation of many materials in the pharmaceutical and food industry. In this perspective, this chapter can develop interest and curiosity among all practicing scientists and technologists by expounding the details of its sources, chemistry, multifunctional properties and applications.",book:{id:"5940",slug:"vitamin-c",title:"Vitamin C",fullTitle:"Vitamin C"},signatures:"Sudha J. Devaki and Reshma Lali Raveendran",authors:[{id:"187911",title:"Associate Prof.",name:"Sudha",middleName:null,surname:"J Devaki",slug:"sudha-j-devaki",fullName:"Sudha J Devaki"},{id:"204937",title:"Mrs.",name:"Reshma",middleName:null,surname:"Laly Ravindran",slug:"reshma-laly-ravindran",fullName:"Reshma Laly Ravindran"}]},{id:"56013",title:"Vitamin C: An Antioxidant Agent",slug:"vitamin-c-an-antioxidant-agent",totalDownloads:7817,totalCrossrefCites:27,totalDimensionsCites:60,abstract:"Vitamin C or ascorbic acid (AsA) is a naturally occurring organic compound with antioxidant properties, found in both animals and plants. It functions as a redox buffer which can reduce, and thereby neutralize, reactive oxygen species. It is a cofactor for enzymes involved in regulating photosynthesis, hormone biosynthesis, and regenerating other antioxidants; which also regulates cell division and growth, is involved in signal transduction, and has roles in several physiological processes, such as immune stimulation, synthesis of collagen, hormones, neurotransmitters, and iron absorption, has also roles in detoxifying the body of heavy metals. Severe deficiency of vitamin C causes scurvy, whereas limited vitamin C intake causes symptoms, such as increased susceptibility to infections, loosening of teeth, dryness of the mouth and eyes, loss of hair, dry itchy skin, fatigue, and insomnia. In contrast, vitamin C can also act as a prooxidant, especially in the presence of transition metals, such as iron and copper, starting different hazardous radical reactions. Vitamin C can both act as a strong, efficient, and cheap antioxidant agent and, at the same time, behave as a radical promoter. Further investigations are needed to illuminate the dual roles of vitamin C",book:{id:"5940",slug:"vitamin-c",title:"Vitamin C",fullTitle:"Vitamin C"},signatures:"Fadime Eryılmaz Pehlivan",authors:[{id:"200567",title:"Dr.",name:"Fadime",middleName:null,surname:"Eryılmaz Pehlivan",slug:"fadime-eryilmaz-pehlivan",fullName:"Fadime Eryılmaz Pehlivan"}]},{id:"69402",title:"Vitamin D Deficiency and Diabetes Mellitus",slug:"vitamin-d-deficiency-and-diabetes-mellitus",totalDownloads:1604,totalCrossrefCites:2,totalDimensionsCites:3,abstract:"Vitamin D (VD) is a molecule that can be synthesized directly in the humans’ body or enter the organism with food in the form of inactive precursors. To exert its biological action, VD undergoes two-stage hydroxylation (at the 25th and 1st position) catalyzed by cytochromes P450, the presence of which has already been shown in almost all tissues of the human body. The product of hydroxylation is hormone-active form of vitamin D–1,25(OH)2D. 1,25(OH)2D binds to specific vitamin D receptor (VDR) and regulates the expression of genes involved in bone remodeling (classical function) and genes that control immune response, hormone secretion, cell proliferation, and differentiation (nonclassical functions). VD deficiency is prevalent around the globe and may be one of the key factors for diabetes development. The direct association between vitamin D deficiency and type 1 (T1D) and type 2 (T2D) diabetes has been proven. Detection of VDR in pancreas and adipose tissue, skeletal muscles, and immune cells allowed implying the antidiabetic role of vitamin D by enhancing insulin synthesis and exocytosis, increasing the expression of the insulin receptor, and modulating immune cells’ functions. This chapter summarizes data about relationship between VD insufficiency/deficiency and development of T1D and T2D, and their complications.",book:{id:"7038",slug:"vitamin-d-deficiency",title:"Vitamin D Deficiency",fullTitle:"Vitamin D Deficiency"},signatures:"Ihor Shymanskyi, Olha Lisakovska, Anna Mazanova and Mykola Veliky",authors:null},{id:"76108",title:"Vitamin D Metabolism",slug:"vitamin-d-metabolism",totalDownloads:498,totalCrossrefCites:2,totalDimensionsCites:3,abstract:"Vitamin D plays an important role in bone metabolism. Vitamin D is a group of biologically inactive, fat-soluble prohormones that exist in two major forms: ergocalciferol (vitamin D2) produced by plants in response to ultraviolet irradiation and cholecalciferol (vitamin D3) derived from animal tissues or 7-dehydrocholesterol in human skin by the action of ultraviolet rays present in sunlight. Vitamin D, which is biologically inactive, needs two-step hydroxylation for activation. All of these steps are of crucial for Vitamin D to show its effect properly. In this section, we will present vitamin D synthesis and its action steps in detail.",book:{id:"10631",slug:"vitamin-d",title:"Vitamin D",fullTitle:"Vitamin D"},signatures:"Sezer Acar and Behzat Özkan",authors:[{id:"29878",title:"Dr.",name:"Behzat",middleName:null,surname:"Özkan",slug:"behzat-ozkan",fullName:"Behzat Özkan"},{id:"348287",title:"Dr.",name:"Sezer",middleName:null,surname:"Acar",slug:"sezer-acar",fullName:"Sezer Acar"}]},{id:"50754",title:"Medicinal Chemistry of Vitamin K Derivatives and Metabolites",slug:"medicinal-chemistry-of-vitamin-k-derivatives-and-metabolites",totalDownloads:1917,totalCrossrefCites:2,totalDimensionsCites:2,abstract:"Vitamin K acts as a cofactor for γ‐glutamyl carboxylase. Recently, various biological activities of vitamin K have been reported. Anti‐proliferative activities of vitamin K, especially in vitamin K3, are well known. In addition, various physiological and pharmacological functions of vitamin K2, such as transcription modulators as nuclear steroid and xenobiotic receptor (SXR) ligands and anti‐inflammatory effects, have been revealed in the past decade. Characterization of vitamin K metabolites is also important for clinical application of vitamin K and its derivatives. 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The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}},{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}}]},series:{item:{id:"24",title:"Sustainable Development",doi:"10.5772/intechopen.100361",issn:"2753-6580",scope:"
\r\n\tTransforming our World: the 2030 Agenda for Sustainable Development endorsed by United Nations and 193 Member States, came into effect on Jan 1, 2016, to guide decision making and actions to the year 2030 and beyond. Central to this Agenda are 17 Goals, 169 associated targets and over 230 indicators that are reviewed annually. The vision envisaged in the implementation of the SDGs is centered on the five Ps: People, Planet, Prosperity, Peace and Partnership. This call for renewed focused efforts ensure we have a safe and healthy planet for current and future generations.
\r\n
\r\n\t
\r\n
\r\n\tThis Series focuses on covering research and applied research involving the five Ps through the following topics:
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\r\n
\r\n\t1. Sustainable Economy and Fair Society that relates to SDG 1 on No Poverty, SDG 2 on Zero Hunger, SDG 8 on Decent Work and Economic Growth, SDG 10 on Reduced Inequalities, SDG 12 on Responsible Consumption and Production, and SDG 17 Partnership for the Goals
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\r\n\t2. Health and Wellbeing focusing on SDG 3 on Good Health and Wellbeing and SDG 6 on Clean Water and Sanitation
\r\n
\r\n\t
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\r\n\t3. Inclusivity and Social Equality involving SDG 4 on Quality Education, SDG 5 on Gender Equality, and SDG 16 on Peace, Justice and Strong Institutions
\r\n
\r\n\t
\r\n
\r\n\t4. Climate Change and Environmental Sustainability comprising SDG 13 on Climate Action, SDG 14 on Life Below Water, and SDG 15 on Life on Land
\r\n
\r\n\t
\r\n
\r\n\t5. Urban Planning and Environmental Management embracing SDG 7 on Affordable Clean Energy, SDG 9 on Industry, Innovation and Infrastructure, and SDG 11 on Sustainable Cities and Communities.
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\r\n\tThe series also seeks to support the use of cross cutting SDGs, as many of the goals listed above, targets and indicators are all interconnected to impact our lives and the decisions we make on a daily basis, making them impossible to tie to a single topic.
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