TNM classification adapted from American Joint Committee on Cancer. AJCC Cancer Staging Manual. 7th edition. New York, NY: Springer, 2010.
\\n\\n
IntechOpen Book Series will also publish a program of research-driven Thematic Edited Volumes that focus on specific areas and allow for a more in-depth overview of a particular subject.
\\n\\nIntechOpen Book Series will be launching regularly to offer our authors and editors exciting opportunities to publish their research Open Access. We will begin by relaunching some of our existing Book Series in this innovative book format, and will expand in 2022 into rapidly growing research fields that are driving and advancing society.
\\n\\nLaunching 2021
\\n\\nArtificial Intelligence, ISSN 2633-1403
\\n\\nVeterinary Medicine and Science, ISSN 2632-0517
\\n\\nBiochemistry, ISSN 2632-0983
\\n\\nBiomedical Engineering, ISSN 2631-5343
\\n\\nInfectious Diseases, ISSN 2631-6188
\\n\\nPhysiology (Coming Soon)
\\n\\nDentistry (Coming Soon)
\\n\\nWe invite you to explore our IntechOpen Book Series, find the right publishing program for you and reach your desired audience in record time.
\\n\\nNote: Edited in October 2021
\\n"}]',published:!0,mainMedia:{caption:"",originalUrl:"/media/original/132"}},components:[{type:"htmlEditorComponent",content:'With the desire to make book publishing more relevant for the digital age and offer innovative Open Access publishing options, we are thrilled to announce the launch of our new publishing format: IntechOpen Book Series.
\n\nDesigned to cover fast-moving research fields in rapidly expanding areas, our Book Series feature a Topic structure allowing us to present the most relevant sub-disciplines. Book Series are headed by Series Editors, and a team of Topic Editors supported by international Editorial Board members. Topics are always open for submissions, with an Annual Volume published each calendar year.
\n\nAfter a robust peer-review process, accepted works are published quickly, thanks to Online First, ensuring research is made available to the scientific community without delay.
\n\nOur innovative Book Series format brings you:
\n\nIntechOpen Book Series will also publish a program of research-driven Thematic Edited Volumes that focus on specific areas and allow for a more in-depth overview of a particular subject.
\n\nIntechOpen Book Series will be launching regularly to offer our authors and editors exciting opportunities to publish their research Open Access. We will begin by relaunching some of our existing Book Series in this innovative book format, and will expand in 2022 into rapidly growing research fields that are driving and advancing society.
\n\nLaunching 2021
\n\nArtificial Intelligence, ISSN 2633-1403
\n\nVeterinary Medicine and Science, ISSN 2632-0517
\n\nBiochemistry, ISSN 2632-0983
\n\nBiomedical Engineering, ISSN 2631-5343
\n\nInfectious Diseases, ISSN 2631-6188
\n\nPhysiology (Coming Soon)
\n\nDentistry (Coming Soon)
\n\nWe invite you to explore our IntechOpen Book Series, find the right publishing program for you and reach your desired audience in record time.
\n\nNote: Edited in October 2021
\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"2517",leadTitle:null,fullTitle:"Autoimmune Diseases - Contributing Factors, Specific Cases of Autoimmune Diseases, and Stem Cell and Other Therapies",title:"Autoimmune Diseases",subtitle:"Contributing Factors, Specific Cases of Autoimmune Diseases, and Stem Cell and Other Therapies",reviewType:"peer-reviewed",abstract:"Autoimmune disease represents a group of more than 60 different chronic autoimmune diseases that affect approximately 6% of the population. Autoimmune diseases arise when ones immune system actively targets and destroys self tissue resulting in clinical disease with prime examples such as Lupus and Type 1 diabetes. \nThe immune system is designed to protect us from foreign pathogens such as viruses and bacteria. However, during the process of generating immune cells for this purpose, as a negative consequence, self-reactive immune cells are also generated. \nThis book aims to present the latest knowledge and insights regarding the different contributing factors and their interplay, discussions on several autoimmune diseases and their case studies, and therapeutic treatments, including stem cell, for autoimmune diseases.",isbn:null,printIsbn:"978-953-51-0693-7",pdfIsbn:"978-953-51-7020-4",doi:"10.5772/2896",price:139,priceEur:155,priceUsd:179,slug:"autoimmune-diseases-contributing-factors-specific-cases-of-autoimmune-diseases-and-stem-cell-and-other-therapies",numberOfPages:404,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"a212e9ae7688cbe123bfb1936b3e3cd4",bookSignature:"James Chan",publishedDate:"July 25th 2012",coverURL:"https://cdn.intechopen.com/books/images_new/2517.jpg",numberOfDownloads:35792,numberOfWosCitations:6,numberOfCrossrefCitations:9,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:20,numberOfDimensionsCitationsByBook:0,hasAltmetrics:1,numberOfTotalCitations:35,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"December 5th 2011",dateEndSecondStepPublish:"January 9th 2012",dateEndThirdStepPublish:"April 14th 2012",dateEndFourthStepPublish:"July 13th 2012",dateEndFifthStepPublish:"August 12th 2012",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"135686",title:"Dr.",name:"James",middleName:null,surname:"Chan",slug:"james-chan",fullName:"James Chan",profilePictureURL:"https://mts.intechopen.com/storage/users/135686/images/system/135686.jpg",biography:"Dr. James Chan’s main research interests focus on tolerance induction, autoimmune diseases, gene therapy and stem cell therapy. It is the aim of combining these areas of research that one day the fruits of this research can benefit patients at the clinic. He conducts his research using two autoimmune disease models, namely diabetes and experimental autoimmune encephalomyelitis (EAE), a model for the human disease multiple sclerosis. There are 2 main areas in his research namely 1) using gene therapy technique to genetically modify haematopoietic stem cells to induce immune tolerance for the treatment of autoimmune disease and 2) the use of stem cells from various tissues such as placental stem cells and bone marrow mesenchymal stem cells for the treatment of autoimmune diseases.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Monash University",institutionURL:null,country:{name:"Australia"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1037",title:"Immunogenetics",slug:"immunogenetics"}],chapters:[{id:"38030",title:"Current Theories for Multiple Sclerosis Pathogenesis and Treatment",doi:"10.5772/50005",slug:"current-theories-for-multiple-sclerosis-pathogenesis-and-treatment",totalDownloads:2886,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:null,signatures:"Marcus Muller, Rachael Terry,\nStephen D. 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The first topic covers the approaches to describing the chaos phenomena in terms of generalized differential equations; the second one describes the different approaches applied to the study of the non-classical dynamical systems. The topic Chaos and Fractals illustrates the application of the cellular automata, non-classical differential equations, and surprising attractors; the appearance of new physical phenomena are discussed in the Chaos in the Classical and Quantum Mechanics. The topic Advances of Chaos describes the novel results in the pure and applied science based on the chaotic background. The application in the Pure Sciences and Technologies covers the achievements based on the characteristics of the chaos fundamentals. Since huge progress on chaos theory predetermines its application in the many areas of pure and applied science, the proposed book will be demanded by many scientists and industrial engineers, as well as post-graduate students and beyond.
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He has been employed by the Pidstryhach Institute for Applied Problems of Mechanics and Mathematics (IAPMM), Ukraine for more than 40 years. Currently, he is the Head of Department of the Numerical Methods in Mathematical Physics at the IAPMM. His professional performance includes more than 160 papers in the scientific journals and international conference proceedings, which concern to the diffraction and antenna synthesis theory, optimization methods and nonlinear integral and matrix equations. He is author of two monographs in antenna theory. 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Globally, it ranks third in incidence after lung and breast cancers. In developed areas such as North America, Australia, New Zealand and Western Europe, it appears even more frequently, being ranked the second [1, 2]. In terms of etiology, it is divided into two categories: genetic and non-genetic. The non-genetic (“sporadic”) category is the most common one (~70–80%), its known cause being the malignant transformation of the adenomatous polyps. This phenomenon occurs over years, related to an unstable lifestyle. An improper diet (low in fruit and vegetables and high in red meat and saturated fat), consumption of toxic products (alcohol and tobacco), obesity, sedentarism, as well as the presence of inflammatory bowel diseases (ulcerative colitis and Crohn’s disease) are all considered as being predisposing factors [3, 4]. In recent years, a decrease in the mortality from colorectal neoplasia and an increase in the survival by up to 5 years has been reported. These are due to the evolution of early detection techniques through screening, as well as to the improved therapeutic procedures. Even if in this disease the prognosis is better than in other cancers, the main concern regards its management which should be directed toward prevention and early diagnosis.
\nScreening methods used are in full development. They are classified into biological assays (for the detection of occult stool blood, DNA, RNA, and feces protein) and colorectal exploration techniques. Among the biological assays, the one used for the detection of occult blood in the stool is the most widely used because of its accessibility, low-cost, and proven effectiveness in reducing the CRC incidence and mortality (by ~15–33%) [4]. The assay for the detection of DNA, RNA, and some proteins in plasma and feces represents another biological category. Due to the variability of literature data related to their diagnosis value as well as their high cost, their usefulness on a large scale is still reduced [4]. The genetic syndromes with increased risk of CRC (the familial adenomatous polyposis and the hereditary non-polyposis colorectal cancer—Lynch syndrome) can be diagnosed through different genetic assays.
\nIn the category of the colorectal exploration tests, optical colonoscopy is the method of choice. This technique is used as a screening assay at different time intervals depending on the probability of disease occurrence. One of its major advantages is the possibility of polyps biopsy/resection (in spite of the high cost and low acceptance by the population!) [4].
\nOther colorectal exploration assays include imaging methods. The techniques used are the double-contrast irrigoscopy and the CT virtual colonoscopy (CT colonography). It is currently recommended to replace the double-contrast irrigoscopy with the CT virtual colonoscopy because of a lower discomfort and a better tolerance, as well as its increasing affordability [5, 6]. There are studies that are showing an increased sensitivity (96%) of the CT virtual colonoscopy, similar to the optical colonoscopy, but the values vary depending on the lesion size [6].
\nThe population at an average risk of developing CRC is represented by subjects older than 50 years old, without other associated risk factors. They can be followed up annually for the detection of occult stool blood, as well as by flexible sigmoidoscopy (only for the left colon, technique that does not require special preparation). The combination of the two assays may be carried out every 5 years. Other availabilities are double-contrast irrigoscopy and virtual colonoscopy done every 5 years, or optical colonoscopy, every 10 years [5–7].
\nThe population with increased risk of developing CRC is represented by subjects with personal or familial history of CRC or adenomatous polyps, those with genetic syndromes, or patients with chronic inflammatory diseases. Each of them can benefit from a customized screening program. The screening program must begin at the age of 40, or 10 years earlier than the age of the youngest relative affected by the disease. The American College of Physicians recommends the use of the optical colonoscopy as a screening method for the high risk population group, noting that the choice of the tests must be carried out according to the risk/benefit ratio, affordability, and the patient’s preferences. In addition, it is recommended to cease the screening in patients over 75 years old or those with a life expectancy of less than 10 years [7].
\nThis category contains a series of diagnostic procedures, the main purpose being that of providing information in the form of images. Every method has specific physical principles, technology, benefits, costs, and limitations. For this reason, each method should be discussed separately.
\nThe ultrasound examination of the digestive tract is a challenge for the performing physician. This is because of the sinuosity of the bowel loops that makes it difficult to perform a full examination using a transducer with a small surface, as well as because of the high air content of the digestive tract, source of sonographic artifacts. It should also be kept in mind that the ultrasound appearance of the digestive structures varies from one time of the examination to another because of the intestinal peristalsis. The ultrasound examination of the digestive tract highly depends on the experience and patience of the examiner, to a much higher extent than the exploration of parenchymal organs. Ultrasonography is the imaging technique with the best space and time resolution in the assessment of the digestive wall, higher than computer-assisted tomography or magnetic resonance imaging. Depending on the frequency of the transducer, we can identify three layers of the wall (when using the convex probe) or five layers (when using the linear probe). Thus, the difficulties of examining the whole digestive tract are offset by a more accurate appreciation of the details.
\nUltrasonography is, on many occasions, the first method of choice for patients with abdominal pain, bowel movements impairments, or other symptoms in the abdominal area [8]. It is a very accessible method, non-irradiating and painless, easily accepted by the patient, and widely available. Also, in many cases, it provides very useful information for patient diagnosis, allowing the exclusion of other diseases with similar symptoms to the CRC. The examining physician must be familiar with the ultrasound appearance of the colon cancer, which is that of a parietal hypoechoic thickening with loss of normal stratification [9]. The extent of the affected colonic wall is variable. Also, the tumor formation can be eccentric, circumferential, or semicircumferential. The colonic lumen can be stenosed [Figure 1]. At palpation with the transducer, the modified region may show an increased stiffness. The pericolic fat has, if invaded by tumor, an “infiltrated” (hyperechogenic) appearance. Peritumoral adenopathies can also be highlighted, with malignant aspect—being hypoechogenic and round [9]. The anorectal administration of contrast fluid (water enema) known as hydrosonography will increase the performance of ultrasonography in diagnosing colon cancer [10] [Figure 2]. A study on 145 patients showed a sensitivity of 79.06% and a specificity of 92.15% for ultrasound in the diagnosis of colon cancer [11], performances which can be improved by the use of hydrosonography. Studies demonstrate that using water enema, the accuracy of the ultrasound in the T staging of the colon cancer increases to 88% and the tumoral infiltration of the lymph nodes can be predicted in approximately 70% of cases.
\nTransabdominal ultrasonography. Appearance of colon cancer.
Transabdominal ultrasonography. Appearance of polypoid tumor. The ultrasonographic image is optimized by hydrosonography (anorectal administration of water).
Asserting the existence of a colonic tumor does not represent a complete diagnosis. We also need to know if the pathological process in the colon is a candidate for a treatment with curative purpose or the disease is in an advanced stage and the patient can only receive palliative treatment. The main reason for which we consider incurable a colon tumor process is the presence of distant metastases. Most often, colon cancer leads to liver metastases [12]. Even if the imaging method recommended for the staging of the colon cancer is computed tomography, ultrasound still plays an important role because it is the first imaging technique currently used. Ultrasound examination improved by the intravenous administration of contrast agents has a complementary role to computed tomography in the characterization of small, hypovascular liver lesions, difficult to be characterized by the means of computed tomography. The ultrasound appearance of the hepatic metastases from colorectal tumors is variable. They are most commonly hypoechoic, but they can also be iso- or hyperechoic [Figure 3]. They are, in most of the cases, surrounded by a hypoechoic halo. The presence of the halo around a focal liver lesion makes it very likely that the lesion is malignant [13]. Sensitivity of ultrasound in the diagnosis of liver metastases is, according to various studies, between 53 and 72%. It is much improved, reaching values of 80–90%, after the administration of an intravenous contrast agent [14, 15]. After the administration of ultrasound contrast media, most of CRC liver metastases will have a hypovascular appearance. In the arterial phase of the examination, they will show peripheral enhancement like a “halo”. Later, during portal/venous phases, this peripheral enhancement will wash out, remaining hypoechoic compared to the liver parenchyma. The portal and especially the late phase will be very important in liver metastases diagnosis; in these phases, they appear like “black spots” on the hyperechoic and shiny background of the normal surrounding parenchyma that captured avidly the contrast agent [Figure 4].
\nTransabdominal ultrasonography (gray scale). Appearance of liver metastases.
Transabdominal ultrasonography with i.v. contrast agent (CEUS). Liver metastases. Peripheral enhancement after contrast administration in the arterial phase (a) and wash-out in the late phase (b).
During abdominal ultrasound in patients with colon tumors, the retroperitoneum must also be assessed. The area between the inferior vena cava and the aorta is the location of metastases in 1–2% of patients with colon cancer. The assessment of this area can be difficult in overweight patients and those with overlap of gas-distended bowel loops. The presence of ascites in a patient with colon tumor raises the suspicion of peritoneal carcinomatosis. The carcinomatosis nodules will be sought mainly in the interhepatophrenic area, at the level of peritoneal recesses, and in the rectovesical space. Searching small-sized carcinoma nodules also requires the assessment of the anterior peritoneum using the high-frequency linear probe [16] [Figure 5].
\nPeritoneal carcinomatosis. Examination was performed with high frequency probe. (a) gray scale ultrasonography and (b) color Doppler ultrasonography).
This is strictly a staging procedure. The rectal ultrasound exploration is only possible through endocavitary approach. The transperineal approach may be used in case of stenosing or prolapsing low rectal tumors in the anal canal, or if the patient shows intolerance to endocavitary procedure. In women, the rectum exploration can be achieved also by endovaginal examination [17]. The preferred ultrasound approach is transrectal, because of the visualization of the five parietal layers and the surrounding organs in the pelvis. From a technical standpoint, the ultrasound device must be equipped with a mechanic and rotating transducer with the frequency between 5–10 MHz. Attached to it there is a rubber bag filled with water (~30–60 ml) (dedicated transducer). In this way, the region to be assessed can be explored more accurately, the ultrasound beam being perpendicular to the rectal wall [18]. Alternatively, the endocavitary transducer for general use can be utilised (adapted equipment). In this case, the ultrasound waves are emitted at an angle of 135 degrees to the plane of the rod, and the obtained information is indicative. However, because of the multidirectional orientation of the examination plan, this equipment can be used to explore larger rectal tumors and even those located in the upper rectum.
\nThere are several ultrasound procedures useful in the diagnosis of rectal tumors. Among them, the ultrasound in “gray scale” allows the analysis of morphological features (the affected parietal layers) [Figure 6]. Doppler ultrasonography and contrast-enhanced ultrasonography (CEUS) provide information about tumor microcirculation by analyzing specific parameters [19–21] [Figure 7]. 3D ultrasound assesses the position of the tumor mass, and it provides the performance of measurements in the three space dimensions using a special transducer [22] [Figure 8]. Sonoelastography is a newly emerging technique and its principle is based on the analysis of the target tissue response (in our case, the tumor tissue) when compressed. Thus, this technique provides information about the degree of the tumor stiffness and surrounding tumoral adenopathies [Figure 9, Figure 10].
\nRectal tumor (a and b). Endorectal gray scale appearance (asterisk).
Rectal tumor investigated with Doppler ultrasound (a) and with CEUS (b). The contrast examination is performed after radiotherapy. Note the partial response to the treatment.
Rectal tumor—multidirectional tridimensional appearance.
Rectal tumor. Gray scale ultrasound (a) and sonoelastographic examination (b). To be noticed the perirectal fat invasion.
Neoplastic perirectal lymphadenopathies (a and b). Sonoelastographic appearance (real-time elastography, color, contact elastography). The marked rigidity of perirectal adenopathies, characteristic of malignancy, is noticed.
The examination takes place after a previous preparation of the patient by an evacuation enema. The patient is positioned in the left lateral decubitus, and the transducer is inserted into the rectum. To optimize the ultrasound image, water can be introduced previously, intrarectally (200–300 ml), but this applies only to patients with sphincter continence and to the compliant ones [22]. Transrectal ultrasound enables the visualization, tracking and assessment of tumor extension to the rectal wall and adjacent organs. The ultrasonographic appearance of rectal infiltrative tumors consists in the presence of circumferential or focal parietal thickening, along with the loss of parietal stratification. Proliferative tumors appear as endoluminal hypoechogenic masses. At the Doppler investigation, they have a disorganized vascularization. At the sonoelastography examination, the tumors are rigid. The staging of rectal cancer through transrectal ultrasound can only be performed locally (T and N stage) because of the reduced field of view of the method. The assessment of tumor invasion in the rectal wall is possible by ultrasound, with an overall diagnosis accuracy of approximately 80–95% [23]. However, the diagnostic performance of the method varies depending on the T stage, being higher for the diagnosis of the rectal tumors in early stages (T1 and T2). This is mainly because of the increased spatial resolution, enabling the differentiation of the rectal wall layers [24]. For the diagnosis of advanced stages, the MRI is preferred because it allows a better visualization of the mesorectum fascia, the peritoneum, and the surrounding organs [25]. Because of the reduced field of view of the transrectal ultrasound, the assessment of the tumoral attaint of the mesorectal fascia is difficult [23]. The tumoral invasion within lymph nodes is another decisive element in determining the therapeutic protocol in patients with rectal cancer. The dimensional and morphological criteria are not sufficient to establish lymph node malignancy. The latest studies show that transrectal ultrasound sensitivity is similar to that of MRI (75.8% versus 77%) for lymph nodes assessment [24, 26].
\nAmong the technical limitations of endocavitary ultrasound is the presence of a tumoral stenosis, which does not allow the transducer to pass the obstacle, thus the tumor cannot be properly assessed. Other limitations are related to post-surgery and post-radiation changes of the rectal wall. The use of the universal endocavitary transducer and the transperineal or transvaginal approach may represent alternative techniques that can provide additional information. Another drawback is differentiating the post-surgery/radiation appearance from a possible tumor residue, or a relapse, and the differentiation of stage T2 from stage T3 can be difficult in some cases because of local inflammatory or fibrotic changes.
\nWater enema CT performed to a 50-year-old female patient with suspicion of adenomatous polyps. (a) Axial and (b) coronal images show a polypoid T2 lesion, located on the lateral wall of the descending colon.
Abdominal CT (including CT virtual colonoscopy) is one of the imaging options in the diagnosis of colon tumors, allowing their detection, characterization, and staging. Discovering a colon tumor under CT can be accidental or in the context of some complications (intestinal obstruction, invagination, perforation, or fistulization) [27]. In terms of the examining technique, it is recommended to perform a luminal distension, with oral contrast, water or air, along with the intravenous administration of the iodinated contrast agent. Currently, it is preferred to replace the oral contrast agent with water, allowing a better individualization of bleeding and tumor iodophilia [27]. A typical CT appearance of a colorectal tumor is that of a polypoid mass [Figure 11] with possible areas of necrosis and air inclusions. Another presentation of CRC is that of an irregular focal or circumferential parietal thickening, associated with endoluminal narrowing or colon stenosis [Figure 12]. The local extracolonic invasion is assessed by the infiltration of the pericolonic fat [Figure 13]. After the administration of the iodinated contrast agent, both the adenomatous polyps and the adenocarcinomas show iodophilia. In the case of a tumoral occlusion, the colon appears dilated upstream of the stenosis and the transition zone is easily viewed using multiplanar reconstructions. The tumoral perforation is more common in the cecum area, and it is detected by the presence of pneumoperitoneum and the infiltration of pericolonic fat [27]. Local staging (stage “T”) of the CRC via CT is difficult because of the impossibility of differentiating its early stages. Erasing the (fatty) cleavage plane between the colon and the surrounding structures (retroperitoneum, anterior abdominal wall, liver, spleen, pancreas, or stomach) suggests their tumoral invasion and it grades the tumor in stage T4 [28].
\nContrast enhanced abdominal CT performed for suspicion of intestinal occlusion. (a) Axial image (portal phase) shows a voluminous iodophilic sigmoid tumor that obstructs the lumen and seems to invade the peritoneum, associated with a thin layer of perilesional fluid. (b) Coronal image shows perilesional fat stranding and the tendency to invagination.
The value of the method for tumoral staging is centered by its ability to identify the local invasion, the lymph nodes, and parenchymal metastases, firstly in the liver, but also peritoneal, in the lungs and within bones. The size of the lymph nodes is not a good indicator of malignancy because tumor foci may exist in the case of small ones too. However, the alteration of lymph nodes may be suspected in CT when there are associated morphological signs. Thus, the presence of an irregular border, a central necrosis, as well as calcifications or a tendency to conglomerate, may all be suggestive of tumoral lymph node invasion [29]. On the other hand, primary tumor location is closely related to the impairment of certain lymph node stations [27].
\nThe most commonly affected organ by distal dissemination of CRC is the liver. The CT appearance of CRC liver metastases is that of hypodense and hypovascular liver masses as compared with the adjacent healthy liver parenchyma [Figure 13]. Sometimes the hepatic metastases reveal the peripheral ring iodophilia during the arterial phase. They may also have a cystic or calcified character; this being often seen in the mucinous colon cancer [27, 29]. CT examination cannot differentiate small liver metastases from benign focal liver lesions. The association of the hepatic steatosis (often seen after chemotherapy) also hinders the diagnosis of liver metastases [30]. However, the abdominal CT with intravenous iodinated contrast, during portal phase, represents the imaging technique of choice for the detection of liver metastases, with high diagnostic accuracy (95%) [5]. The distal dissemination of the (lower) rectal cancer can take place only in the lungs without affecting the liver because of the venous drainage of the rectum (in the inferior vena cava). The chest CT can detect lung metastases that have a unique nodular appearance, sometimes cavitary or calcified. Lymphangitic carcinomatosis associated with pleural effusion is another form of pulmonary metastasis [29, 30]. Peritoneal dissemination is identifiable by the presence of peritoneal thickening and of the tumoral deposits in the omentum, associated with intra-abdominal fluid collections. Bone metastases are rare, and they have a lytic or mixed appearance (lytic and sclerotic) [30]. Brain metastases from colorectal cancer do not have a specific CT appearance, and they cannot be distinguished in imaging from those with other origin [30].
\nAbdominal CT scan of a 60-year-old male with colon cancer. Axial image (portal phase) shows a tumoral thickening of the colonic wall associated with pericolonic fat stranding, some extra-luminal gas bubbles (tumor perforation) and liver metastases (in segments I and VI).
CT virtual colonoscopy is a minimally invasive imaging technique that allows the assessment of both colon and rectum, and also of the extracolonic organs. Its use as a screening method in CRC is much discussed in the literature. Studies about the sensitivity and specificity of this method are varied but the highest values of sensitivity were obtained for the detection of polyps with sizes over 10 mm (95%) [5, 6]. Despite some controversy, CT virtual colonoscopy is useful in elderly subjects with comorbidities, in case of an incomplete optical colonoscopy or if the patient refuses it [5, 6]. Another indication is the evaluation of the entire colon for the exclusion of a synchronous cancer. In addition, a balance of the disease extension can be performed if the examination is made using intravenous contrast agent [5, 31]. The most important contraindications are the acute colic disease (diverticulitis, inflammatory bowel disease in acute stages), presence of intestinal perforation, recent post-polypectomy or immediately after surgery [31, 32]. It is necessary to prepare the colon 24 hours before the examination. This is possible through a diet low in fiber and administration of sodium phosphate, magnesium citrate, or polyethylene glycol. The administration of oral barium or iodine contrast agents allows the “tagging” of the residual stool deposits and the differentiation from colonic polyps. Another method of preparation consists of the use of an oral hyperosmolar contrast agent, thereby achieving an increase in patient compliance [33, 34]. The next step in performing a virtual colonoscopy is the luminal distension by air or by carbon dioxide, under pressure control through a rectal tube. In practice, the carbon dioxide is preferred because of an increased tolerance of the patient and its absorption in the colon mucosa [31, 34]. The acquired images are analyzed in at least two positions (supination and pronation, sometimes lateral decubitus), which allows the differentiation of the colon polyps from residual stool deposits [34]. The interpretation is done by analyzing the 2D and 3D images, along with virtual endoluminal navigation. There is also a software (Computer Aided Detection—CAD) that automatically detects the lesions in the colon. This facilitates lesion detection but it should not exclude the primary analysis of 2D and 3D images [34]. Lesion characterization and classification is possible using the reporting system according to the model “CT Colonography Reporting and Data System (C-RADS)” [35]. This system allows the location, the morphological (sessile, flat, or pedicle tumor), and dimensional analysis of the detected lesion. C0 suggests an inadequate examination and C1 represents the normal appearance of the colon. C2 lesions represent their indeterminate character and they refer to identification of less than three polyps with the diameter between 6 and 9 mm. C3 lesions are represented by either a polyp over 10 mm, or more than three polyps ranging in size from 6 to 9 mm. C4 lesions describe the presence of a colonic tumor mass, with luminal narrowing or the invasion of adjacent organs [32, 35]. The main disadvantages of this method are irradiation (currently decreasing!) and the impossibility to perform biopsy or to treat the detected lesions. There is also a great variability among examiners in image interpretation because of different levels of experience [33].
\nWater enema CT is applicable in the case of an inconclusive or impossible optical colonoscopy [36]. The method involves luminal distension of the colon by water enema for about 3 minutes. Water is introduced through an endorectal tube connected to a bag with a volume of approximately 2 L. Initially, images are acquired without the intravenous administration of contrast agent, followed by a post-contrast acquisition. At the end of the examination, the colonic content is discharged by simply lowering the enema bag. Image interpretation is possible in the axial plane with the reconstruction in all three space dimensions [28]. Luminal distension of the colon with water provides a good contrast between the colonic wall and its luminal content. The tumor-free colonic wall is thin, regular, with a thickness below 3 mm and an enhancement in portal phase [28, 36]. A colorectal tumor may appear as an endoluminal polypoid lesion or as a semi- or circumferential irregular parietal thickening, with heterogeneous iodophilia [28]. Some studies show a high accuracy of the method in differentiating the T1-2 tumors from the T3-4 ones. A study performed on a group of 53 patients reveals that the deep parietal invasion (T3-T4) is suggested by the irregular appearance of the outer (peritoneal) tumor margin associated with an angular transition area to the healthy colon [37]. Besides the loco-regional staging (T), the water enema CT allows the overall assessment of the distal colorectal tumor dissemination, with the simultaneous detection of the liver metastases and peritoneal carcinomatosis [37]. Finally, water enema CT is an imaging technique useful in the CRC diagnosis, staging, and characterization because it is cheap, accessible, and easy to perform. In addition, it is easily accepted by patients and it requires no previous colon preparation [28, 37].
\nThe situation in which we may incidentally detect a colon tumor upon acquiring MRI scans of the abdomen for other purposes is rare. The MRI appearance of the colic tumor is non-specific. Generally, there is a thickening of the colonic wall, with loss of stratification and a slight hypersignal on T2 sequence with fat suppression. The pericolic fat infiltration and the presence of perilesional adenopathies are important additional signs, which may direct the diagnosis toward a colonic tumoral pathology. From a practical standpoint, however, the radiologist must refer toward gastroenterology and colonscopy every patient without known enteral pathology, with suspect thickening of the colon wall. The preferred imaging technique for the staging of colon tumors is computed tomography. Computed tomography has the advantage that allows, on a single imaging examination, to assess both the abdominal and thoracic cavities, including bones and lungs. However, there are situations where the physician can request abdominal MRI for staging an initial colon cancer.
\nPelvis MRI, T2 weighted images, axial section. Rectal tumor prominent in rectal lumen. Note that the tumor does not surpass the thin line in hyposignal representing the muscular layer and the perirectal fat is homogeneous. The appearance suggests a T2 stage tumor.
Pelvis MRI, T2 weighted images, axial section. Circumferential rectal tumor, extending into all wall layers and invading the perirectal fat, in right lateral and posterior area.
Because of the critically important information it offers, pelvic MRI examination is mandatory in staging rectal tumors. The sequences to be achieved primarily are the high resolution (HR) T2 weighted images, in all three planes. The examination shall be completed with diffusion sequences. The injection of the intravenous contrast agent is not needed in the local staging of rectal cancer. On the HR T2 sequences, a rectal tumor will appear slightly in hypersignal reported to parietal muscles, and respectively in hyposignal reported to perirectal fat. Because of the existing contrast between the tumor, on the one hand, and the perirectal fat, on the other hand, we do not recommend using the fat suppression. Fat suppression will lead to the underestimation of the perirectal extension of the tumoral process. Most of the times the rectal lumen will also have a content in hypersignal in the plane of the tumor because of mucin secretion. In tumoral stages T1 and T2, tumor growth is limited to the rectal wall [Figure 14]. In tumoral stage T1, the tumoral growth does not exceed the submucosa, and in stage T2 it does not exceed the muscularis layer. The MRI examination is not accurate in differentiating tumor stages T1 and T2, but it is very good in determining the existence or absence of the tumoral invasion of the perirectal fat (it can thus differentiate tumors limited to the rectal wall, stages T1 and T2, from the ones extending outside the wall). MRI has a great accuracy in determining the depth of the perirectal invasion [38]. Most of rectal tumors (approximately 80%) will be in T3 stage when imaging diagnosis is performed [Figure 15]. Because the depth of the perirectal invasion is an important independent prognostic factor for the survival and chances of curing a rectal tumor, the layering of T3 stage according to the depth of the invasion was necessary (Table 1). Thus it is considered that a depth of the perirectal invasion higher than 5mm will lead to a decrease in the survival expectancy at 5 years, from 85 to 54% [39]. The invasion of adjacent organs or structures (bladder, prostate, or seminal vesicles, uterus or ovaries, vagina, peritoneum recesses, the levator ani muscles or the pelvic wall) is considered T4 stage [Figure 16]. Apart from a correct local staging, the MRI examination must provide information related to the relationship between the tumor and certain surrounding structures. One of these structures is the mesorectal fascia. A mesorectal fascia without tumoral invasion will allow the total excision of the mesorectum, as this surgical procedure leads to the smallest chance of tumor recurrence. To consider mesorectal fascia as invaded, it is necessary that the tumor exceed it,or that tumoral tissue exists less than 1 mm away from the fascia (the tumoral tissue can be represented either by a direct extension of the tumoral mass, by tumoral deposits within the mesorectum, or by the presence of metastatic lymph nodes). Establishing the invasion or the relationship the tumor has with the mesorectal fascia is one of the advantages of magnetic resonance imaging as compared with transrectal ultrasound. The peritoneum recess is reflected on the upper side of the urinary bladder and on the anterior wall of the upper rectum to form the rectovesical recess. Its invasion is difficult to reveal and it requires knowledge of the normal anatomy. Tumors that will invade the peritoneum will be staged as T4a. Also, MRI examination is superior to transrectal ultrasound in establishing the existence of peritoneal invasion. Furthermore, the existence of invasion of the anal sphincter should be established before surgery because it has great significance in the preoperative planning. It is considered that in the cases of tumoral extension to the rear side of the pubis-rectal muscles, the surgery with the preservation of the anal sphincter is not feasible. In the case of tumors with sphincter infiltration its extension and the interested structures should be carefully specified on the imaging report because, according to this extension, we will be able to determine whether it is possible or not to perform recto-anal reconstruction procedures or if the patient will be a candidate for the rectum amputation.
\nTumoral mass | \n|
Tx | \nDetermination of tumor extension cannot be assessed on the performed examination | \n
T1 | \nTumor has not spread deeper than the submucosa | \n
T2 | \nTumor invades muscularis propria, but does not extend into the perirectal fat | \n
T3 | \nTumor grows through the muscularis propria in mesorectum | \n
T3a | \nTumor extends to a depth less than 5 mm beyond the muscularis propria | \n
T3b | \nTumor extends 5–10 mm from muscularis propria | \n
T3c | \nTumor extends more than 10 mm from muscularis propria | \n
T4a | \nTumor invades visceral peritoneum | \n
T4b | \nTumor invades organs and structures near the rectum | \n
Adenopathies | \n|
Nx | \nLymph node staging cannot be assessed on the performed examination | \n
N0 | \nNo obvious metastatic adenopathies | \n
N1a | \nTumor invades one lymph node | \n
N1b | \nTumor invades two or three lymph nodes | \n
N1c | \nTumoral deposits in the subserosa, mesentery, non-peritonealized pericolic, or perirectal tissues without lymph node metastasis | \n
N2a | \nMetastasis in four up to 6 lymph nodes | \n
N2b | \nMetastasis in seven or more lymph nodes | \n
M0 | \nNo distant metastasis (other than in regional lymph nodes) | \n
M1a | \nDistant metastasis confined to one organ | \n
M1b | \nDistant metastasis in more organs or peritoneal carcinomatosis | \n
TNM classification adapted from American Joint Committee on Cancer. AJCC Cancer Staging Manual. 7th edition. New York, NY: Springer, 2010.
Lymph nodes that must be assessed during the staging of a rectal tumor belong to the following groups: mesorectum, superior rectal, inferior mesenteric, internal and external iliac, retroperitoneal, and inguinal areas. The most commonly affected lymph nodes are the ones located at mesorectal level, inside the mesorectal fascia. However, it is also important to mention if we consider that lymph nodes located outside the mesorectal fascia are affected by tumoral metastases—they will have to be surgically excised to avoid relapse, or the preoperative radiation therapy should be done on a broader field. If transrectal ultrasound is considered to have roughly similar performances to MRI in revealing the existence of mesorectal lymph nodes, MRI will certainly be better in diagnosing the presence of lymph nodes located outside the mesorectal fascia. MRI is still limited in revealing the malignant or benign character of the detected lymph nodes. Thus, if we use the classic criterion linked to the size of the lymph nodes, using a limit of 5 mm to differentiate the benign lymph nodes from the malignant ones, we will have a sensitivity of 68% and a specificity of 78% for the diagnosis of malignancy [40]. The accuracy of this criterion in the differential diagnosis of benign/malignant perirectal adenopathies is more limited as, between 30 and 50% of the metastatic adenopathies have diameters of less than 5 mm [41]. An irregular outline of lymph nodes, associated with non-homogeneity of the signal inside them, would be considered as being a key indicator of malignancy [40].
\nPelvis MRI, T2 weighted images, coronal section. Rectal tumor with invasion of the perirectal space. Inferior and on the right side the tumor determines the invasion of the levator ani muscles.
It is considered that PET-CT does not bring additional information compared with thoraco-abdomino-pelvic CT in the initial staging of colon cancer [42, 43]. There are two situations where PET-CT is recommended in patients with colorectal tumors: (a) patients in which the values of the carcinoembryonic antigen are growing during oncological monitoring and the conventional imaging cannot detect the location of the tumoral recurrence and (b) patients with single liver metastasis, candidates for liver resections. It is considered that, in these patients, performing PET-CT before surgery leads to a decrease in the number of useless laparotomies [44, 45]. It is believed that chemotherapy decreases the sensitivity of PET-CT for diagnosing the colorectal cancer metastases. For this reason, in patients which are potential candidates for liver metastasectomy, we prefer to perform the PET-CT examination before starting chemotherapy to detect other possible tumoral locations.
\nMost of the times colon tumors are identified through colonoscopy, and imaging helps staging these tumors. If the tumor is located in the colon, the initial staging will be done through abdominal ultrasound and thoraco-abdomino-pelvic CT. In most cases, this will be sufficient for an accurate staging and the images will be later used as reference for the post-treatment examinations. In case lesions detected are considered as being indeterminate, with non-specific computer-tomographic and ultrasound appearance, it will be necessary to complete with other imaging examinations or sampling via an intraoperative biopsy or percutaneous punctures. The imaging techniques that can be used in this situation are contrast enhanced ultrasound (CEUS), magnetic resonance imaging (MRI) or PET-CT. The rectal tumors will benefit from the high-resolution pelvic MRI or transrectal ultrasound for their initial staging. There are situations in which we will find colon tumor formations incidentally in the course of imaging explorations performed for other purposes or for non-specific symptoms. In these cases, we should be advised first of all on the imaging appearance of such tumors. Then, we shall refer to colonoscopy for the confirmation of the existence of a tumoral process.
\nThe staging of the tumor will be made in the same manner as in the case of the tumors diagnosed through colonoscopy. The imaging monitoring of the patients treated for colonic tumors is made through computerized tomography every 6 months. Because of the difficulties in the detection and diagnosis of small liver metastases through computed tomography, our work team recommends to complete the investigations with a liver ultrasound. The images will be permanently correlated with those obtained prior to the treatment, and the lesions with undetermined appearance will benefit from additional diagnostic investigations, similar to those described in the initial staging of the colon tumors. In the patients with tumors found in a later stage, which cannot benefit from curative treatments, it is recommended that the monitoring by thoraco-abdomino-pelvic computer-tomography be made even more often (every 3 months) to evaluate the efficiency of the administered chemotherapy. If, after a series of examinations, the disease evolution is clear, an early change of the chemotherapy scheme can lead to an increased life expectancy.
\nThe patients with operated rectal tumors, especially those who have received neoadjuvant radiotherapy, may receive the recommendation to undergo the pelvic MRI periodically, complementary to the thoraco-abdomino-pelvic computed tomography. This is because MRI is more accurate, compared with the computed tomography, in the differentiation of the tumoral relapses in the pelvic area from the post-irradiation fibrosis.
\nThe occurrence of side effects after vaccination is a normal phenomenon; most side effects are local reactions and systemic effects are usually rare [1].
The safety of COVID-19 vaccines has been closely monitored during clinical trials, but even now, during their use, both local and systemic adverse reactions occur immediately after administration and delayed reactions [1].
Several types of COVID 19 vaccines have been used or are being used (Table 1):
Vaccine | Trade-named | Type |
---|---|---|
Pfizer–BioNTech COVID-19 | Comirnaty | mRNA vaccine1 |
Moderna COVID-19 | Spikevax | mRNA vaccine1 |
Janssen COVID-19 | Johnson & Johnson COVID-19 | Viral vector vaccine2 |
Oxford–AstraZeneca COVID-19 | Vaxzevria, Covishield | Viral vector vaccine3 |
Sinopharm BIBP COVID-19 | BBIBP-CorV | Inactivated virus vaccine4 |
CoronaVac COVID-19 | Sinovac COVID-19 | Inactivated virus vaccine4 |
Gam-COVID-Vac | Sputnik V | Viral vector vaccine5 |
NVX-CoV2373 | Novavax COVID-19 | Protein subunit vaccine and a virus-like particle vaccine, though the producers call it a “recombinant nanoparticle vaccine”6 |
BBV152 | Covaxin | Inactivated virus vaccine4 |
AD5-nCOV | Convidecia | Viral vector vaccine7 |
CIGB-66 | Abdala | Subunit vaccine8 |
EpiVacCorona | Peptide vaccine9 | |
ZF2001 | Zifivax | Subunit vaccine7 |
FINLAY-FR-2 | Soberana 02 | Conjugate vaccine10 |
CoviVac | Inactivated virus vaccine4 | |
VLA2001 | Valneva COVID-19 vaccine | Inactivated virus vaccine4 |
QazCovid-in | QazVac | Inactivated virus vaccine4 |
Minhai COVID-19 vaccine | KCONVAC | Inactivated virus vaccine4 |
COVIran Barekat | Inactivated virus-vaccine4 | |
Chinese Academy of Medical Sciences COVID-19 vaccine IMBCAMS COVID-19 vaccine | Covidful | Inactivated virus vaccine4 |
MVC-COV1901 | Medigen | Protein subunit vaccine6 |
ZyCoV-D | DNA plasmid based COVID-19 vaccine11 | |
FAKHRAVAC | MIVAC | Inactivated virus vaccine4 |
COVAX-19 | SpikoGen | Protein subunit vaccine6 |
Razi Cov Pars | Protein subunit vaccine6 | |
Turkovac | ERUCOV-VAC | Inactivated virus vaccine4 |
Sinopharm CNBG COVID-19 vaccine | Recombinant protein subunit vaccine6 | |
Corbevax | Protein subunit vaccine6 | |
FINLAY-FR-1A, | Soberana Plus | Conjugate vaccine10 |
CoVLP | Virus-Like Particle vaccine12 | |
Noora | Protein-based vaccine6 |
COVID-19 vaccines [2].
type of vaccine that uses a copy of a molecule called messenger RNA (mRNA) to produce an immune response.
adenovirus serotype 26.
chimpanzee adenovirus ChAdOx1.
vaccine consisting of virus particles that have been grown in culture and then killed to destroy disease-producing capacity.
adenovirus serotype 26 for the first shot and serotype 5 for the second.
the vaccine that contains purified parts of the pathogen that are antigenic, or necessary to elicit a protective immune response.
adenovirus serotype 5.
contains purified parts of the pathogen that are antigenic.
subunit vaccines made from peptides.
type of subunit vaccine which combines a weak antigen with a strong antigen as a carrier so that the immune system has a stronger response to the weak antigen.
type of vaccine that transfects a specific antigen-coding DNA sequence into the cells of an organism as a mechanism to induce an immune response.
molecules that closely resemble viruses, but are non-infectious because they contain no viral genetic material.
The most common local effects after vaccination are pain, redness, and swelling at the injection site [3]. In a study conducted in the Czech Republic, on 922 health workers, local pain was reported in 89.8% of cases, after the administration of Pfizer-BioNTech COVID-19 vaccine [4]. Side effects after the second shot may be more intense than the ones experienced after the first shot [3].
Tiredness, headache, muscle aches, chills, joint pain, and fever (more common after the second dose) were also reported [5].
In his paper published in 2021, Meo et al. [6] analyzed the most recent and eloquent data on the side effects of the 2 RNA vaccines, Pfizer-BioNTech COVID-19 and Moderna, data published in the Web of Science (Clarivate Analytics), PubMed, EMBASE, World Health Organization (WHO), Food and Drug Authorities (FDA) USA, Local Ministries, Health Institutes, and Google Scholar. It was found that the most common reactions caused by administration of the first dose vaccine of Pfizer-BioNTech COVID-19 were pain, swelling, redness, fever, fatigue, headache, chills, vomiting, diarrhea, muscle pain, joint pain, lymphadenopathy, shoulder injury, right axillary lymphadenopathy, paroxysmal ventricular arrhythmia, syncope, and right leg paresthesia [7]; and pain, swelling, redness at the site of vaccine, fever, fatigue, headache, chills, vomiting, arthralgia, myalgia, and urticaria after the first dose of Moderna vaccine (Figure 1) [7]. Moderate or severe reactions have been reported after the second dose of vaccine, and facial swelling and Bell’s palsy have also been reported [8].
Comparison between frequencies of adverse effects of Pfizer-BioNTech and Moderna vaccines [
Also, the most common reactions after administration of the most commonly used vaccines are shown in the Table 2 [2].
Vaccine | Side effects prevalence | Common Side effects |
---|---|---|
Pfizer-BioNTech COVID-19 | < 1 in 10 people. | Pain and swelling at the injection site, tiredness, headache, muscle aches, chills, joint pain, and fever |
< 1 in 1000 people | Temporary one-sided facial drooping and allergic reactions such as hives or swelling of the face | |
Moderna COVID-19 | < 1 in 10 people. | Pain at the injection site, fatigue, headache, myalgia (muscle pain), and arthralgia (joint pain) |
< 1 in 1000 people | Delayed cutaneous reactions at injection site resulting in rash-like erythemas | |
Janssen COVID-19 | < 1 in 10 people. | Pain and swelling at the injection site, redness, headache, tiredness, muscle pain, nausea, coughing, joint pain, fever, and chills |
< 1 in 100 people. | sneezing, tremor, throat pain, rash, sweating, muscle weakness, pain in the arms and legs, backache, weakness, and feeling generally unwell | |
< 1 in 1000 people | hypersensitivity (allergy), and itchy rash | |
Oxford-AstraZeneca COVID-19 | < 1 in 10 people | Vomiting, diarrhea, fever, swelling, redness at the injection site, and low levels of blood platelets |
< 1 in 100 people. | Enlarged lymph nodes, decreased appetite, dizziness, sleepiness, sweating, abdominal pain, itching, and rash | |
< 1 in 1000 people | Hypersensitivity (allergy) |
The most common reactions after administration of Pfizer-BioNTech, Moderna, Janssen, and Oxford-AstraZeneca vaccines [2].
Most side effects were mild and moderate, and severe allergic reactions were rare [10]. In patients who have experienced severe side effects after receiving the first dose of mRNA vaccines, dose 2 has not been given. Also, no other dose was given to patients who experienced severe allergic reactions after COVID 19 Janssen or Oxford-Astra Zeneca vaccines [10].
Documented hypersensitivity to polyethylene glycol (PEG) is a contraindication to the COVID-19 Pfizer vaccine, severe allergic reaction has been observed in about 10 cases per million doses of vaccine administered [11].
According to the Center for Disease Control (CDC), the 15-minute postvaccination monitoring recommendation is certified by the fact that most allergic reactions (71%) occur during this period, especially in patients with a history of allergic events (81%) [11].
Anaphylaxis after COVID-19 vaccination is rare with rates of 4.7 cases/million Pfizer-BioNTech vaccine doses administered and 2.5 cases/million Moderna vaccine doses administered [12]. In cases where anaphylaxis has been reported, it has occurred within the first 15 minutes of receiving the vaccine, especially at the first dose of vaccine, usually in people who have reported allergic reactions or anaphylaxis in their medical history [13].
Myocarditis and pericarditis after COVID-19 vaccination are rare. Most cases have been reported after receiving Pfizer-BioNTech or Moderna (mRNA COVID-19 vaccines), particularly in male adolescents and young adults [14]. Most of them (95%) had mild or moderate manifestations, self-limiting in most cases, and did not require hospitalization for more than four days [15, 16]. Myocarditis has been reported more often after the second dose, usually within a week of vaccination [14].
According to the Vaccine Adverse Event Reporting System (VAERS), a significant number of cases of myocarditis have been reported in young people, after the administration of mRNA vaccine, especially the second dose, with favorable evolution under specific treatment and hospitalization [17].
Related to the age group, most cases were reported in young people in the 16–17 age group (105.9 cases per one million doses) [17], followed by the 12–15 age group (70.7 cases per one million doses) and 18–24 age group (52.4 cases per million doses) [17].
In the study published in August 2021 by Diaz et al., myocarditis occurred a median of 3.5 days (IQR, 3.0–10.8 days) after mRNA vaccination, the median age was 36 years (IQR, 26–48 years), all were discharged after a median of 2 days (IQR, 2–3 days), and there were no readmissions or deaths [18].
Pericarditis developed especially after the second immunization, median onset was 20 days (IQR, 6.0–41.0 days) after the vaccination, median age was 59 years (IQR, 46–69 years median stay in hospital was 1 day (IQR, 1–2 days), no deaths were reported [18].
Thrombosis with thrombocytopenia syndrome (TTS) has been associated with the administration of the Janssen COVID-19 vaccine [19]. TTS is rare and has occurred in approximately 4 cases per one million doses administered [19]. A review of reports indicates a causal relationship between the Janssen COVID-19 vaccine and TTS [20, 21].
The following features were found in relation to TTS [20, 21]:
All side effects have been reported after the first dose of the Janssen COVID-19 vaccine (none after booster doses).
Median time from vaccination to symptom onset: 9 days (range 0–18 days).
48% are women aged <50 years.
Median age: 44.5 years (range 18–70 years).
83% in White non-Hispanic persons.
54% have a cerebral venous sinus thrombosis (CVST).
Venous thrombosis risk factors in U.S. TTS cases following Janssen COVID-19 vaccination are [20, 21]: obesity (46%), hypertension (30%), diabetes (13%), and systemic estrogen therapy (6%).
Thrombotic adverse events have also been reported following the administration of the Oxford-AstraZeneca COVID-19 vaccine, especially in younger women [19, 22]. Analysis of VigiBase reported embolic and thrombotic events after vaccination with Oxford-AstraZeneca, found a related incidence of 0.21 cases per 1 million vaccinated-days [23].
The following characteristics were found in cases with TTS in connection with Astra Zeneca COVID-19 vaccination [19]:
TTS developed 5 to 24 days after initial vaccination.
Women younger than 50 years of age, some of whom were receiving estrogen replacement therapy or oral contraceptives.
Patients were known to have had previous thrombosis or a preexisting prothrombotic condition.
A high percentage of the patients had thromboses at unusual sites (cerebral venous sinus thrombosis or thrombosis in the portal, splanchnic, or hepatic veins).
The median platelet counts at diagnosis were approximately 20,000 to 30,000 per cubic millimeter (range, approximately 10,000 to 110,000).
Guillain-Barré syndrome (GBS) in people who have received the Janssen COVID-19 vaccine is a very rare side effect and was reported during the 42 days following vaccination, especially in men ages 50 years and older [24].
Based on a recent analysis of data from the Vaccine Safety Datalink, the rate of GBS was 11 times higher following Janssen COVID-19 vaccination compared to Pfizer-BioNTech or Moderna (mRNA COVID-19 vaccines) [25].
In a study, conducted by Miguel García-Grimshaw and published in August 2021, on more than 3 million people who received mRNA vaccines, GBS was very rare, with incidence of 0.18/100,000 administered doses, within 30 days from first dose vaccine administration [26]. No cases were reported after second dose administration [26]. The presence of a concomitant trigger in most of our cases suggests a lack of mechanistic connection between mRNA vaccines and GBS [26].
Delayed hypersensitivity reactions after the administration of vaccines for COVID-19 have been reported, a median of 7 days after the first vaccine dose, mainly after administration of mRNA vaccines [27]. Delayed large local reactions were noted as well urticaria, morbilliform eruptions, erythromelalgia, erythema multiforme, vasculitis, petechiae, pityriasis-rosea-like exanthems, or persistent maculopapular exanthema [28, 29]. Angioedema and liver damage were also described [28, 29].
A number of very rare side effects have been reported with various vaccines:
A rare autoimmune neurologic disorder characterized by ascending weakness and paralysis after Janssen COVID-19 vaccination [30]
Ocular adverse effects like facial nerve palsy, abducens nerve palsy, acute macular neuroretinopathy, central serous retinopathy, thrombosis, uveitis, multiple evanescent white dot syndrome, Vogt-Koyanagi-Harada disease reactivation, and new-onset Graves’ Disease [31]
Reactive arthritis (ReA) after CoronaVac vaccination [32]
Auto-immune hepatitis following Covishield vaccination [33]
Sudden sensorineural hearing loss after Oxford-AstraZeneca Covid-19 vaccination [34]
Bullous pemphigoid rash following Moderna [35]
Interstitial lung disease after BNT162b2 mRNA COVID-19 vaccine [36]
COVID-19 vaccines are safe and effective; most side effects are mild and moderate and resolve in a few days. Severe reactions after vaccination are rare; however, the benefit of vaccination is much greater than the risk.
IntechOpen has always supported new and evolving ideas in scholarly publishing. We understand the community we serve, but to provide an even better service for our IntechOpen Authors and Academic Editors, we have partnered with leading companies and associations in the scientific field and beyond.
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Contreras",coverURL:"https://cdn.intechopen.com/books/images_new/1592.jpg",editedByType:"Edited by",editors:[{id:"35182",title:"Dr.",name:"Carlos M.",middleName:null,surname:"Contreras",slug:"carlos-m.-contreras",fullName:"Carlos M. Contreras"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:2,seriesByTopicCollection:[],seriesByTopicTotal:0,mostCitedChapters:[{id:"32399",doi:"10.5772/36092",title:"Brain Energy Metabolism in Health and Disease",slug:"brain-energy-metabolism-in-health-and-disease",totalDownloads:9132,totalCrossrefCites:1,totalDimensionsCites:10,abstract:null,book:{id:"1592",slug:"neuroscience-dealing-with-frontiers",title:"Neuroscience",fullTitle:"Neuroscience - Dealing With Frontiers"},signatures:"Felipe A. Beltrán, Aníbal I. Acuña, María Paz Miró and Maite A. Castro",authors:[{id:"107041",title:"Dr.",name:"Maite A",middleName:null,surname:"Castro",slug:"maite-a-castro",fullName:"Maite A Castro"},{id:"109692",title:"Mr.",name:"Felipe A",middleName:null,surname:"Beltran",slug:"felipe-a-beltran",fullName:"Felipe A Beltran"},{id:"109695",title:"Mr.",name:"Aníbal",middleName:"I.",surname:"Acuña",slug:"anibal-acuna",fullName:"Aníbal Acuña"},{id:"109696",title:"Ms.",name:"Maria Paz",middleName:null,surname:"Miro",slug:"maria-paz-miro",fullName:"Maria Paz Miro"}]},{id:"54565",doi:"10.5772/67828",title:"The Role of the Amygdala in Regulating the Hypothalamic-Pituitary-Adrenal Axis",slug:"the-role-of-the-amygdala-in-regulating-the-hypothalamic-pituitary-adrenal-axis",totalDownloads:3554,totalCrossrefCites:6,totalDimensionsCites:9,abstract:"We investigated the regulatory role of the amygdala upon the function of the hypothalamic-pituitary-adrenal (HPA) axis as measured by median eminence corticotrophin releasing hormone (CRH) content and serum levels of adrenocorticotrophic hormone (ACTH) and corticosterone. Our findings showed that (1) lesions of the central amygdala inhibited the HPA axis responses to a variety of stressful stimuli. (2) Depletion of norepinephrine or serotonin in the amygdala and hypothalamus and local injections of norepinephrine and serotonin receptor antagonists into the central amygdala inhibited the HPA axis responses to neural stress. Norepinephrine and serotonin agonists injected into the amygdala caused an increase in HPA axis activity. The activation of the amygdala facilitated the in vivo release of serotonin from the paraventricular nucleus following electrical stimulation of the brainstem raphe nuclei. (3) Electrical stimulation of the amygdala impaired the glucocorticoid negative feedback action following neural stressful stimuli probably via a decrease in hippocampal corticosteroid receptors.",book:{id:"5485",slug:"the-amygdala-where-emotions-shape-perception-learning-and-memories",title:"The Amygdala",fullTitle:"The Amygdala - Where Emotions Shape Perception, Learning and Memories"},signatures:"Joseph Weidenfeld and Haim Ovadia",authors:[{id:"190851",title:"Ph.D.",name:"Haim",middleName:null,surname:"Ovadia",slug:"haim-ovadia",fullName:"Haim Ovadia"},{id:"192823",title:"Prof.",name:"Joseph",middleName:null,surname:"Weidenfeld",slug:"joseph-weidenfeld",fullName:"Joseph Weidenfeld"}]},{id:"32393",doi:"10.5772/34852",title:"The Neurochemical Anatomy of Trigeminal Primary Afferent Neurons",slug:"the-neurochemical-anatomy-of-trigeminal-primary-afferent-neurons",totalDownloads:4712,totalCrossrefCites:0,totalDimensionsCites:9,abstract:null,book:{id:"1592",slug:"neuroscience-dealing-with-frontiers",title:"Neuroscience",fullTitle:"Neuroscience - Dealing With Frontiers"},signatures:"Nikolai E. Lazarov",authors:[{id:"101891",title:"Prof.",name:"Nikolai",middleName:null,surname:"Lazarov",slug:"nikolai-lazarov",fullName:"Nikolai Lazarov"}]},{id:"54301",doi:"10.5772/67585",title:"Revisiting the Role of the Amygdala in Posttraumatic Stress Disorder",slug:"revisiting-the-role-of-the-amygdala-in-posttraumatic-stress-disorder",totalDownloads:2172,totalCrossrefCites:2,totalDimensionsCites:8,abstract:"Over the past 20 years, the reactivity of amygdala to emotive stimuli has been explored by emerging neuroimaging techniques in an effort to understand the role of amygdala in the pathophysiology of posttraumatic stress disorder (PTSD). A fear neurocircuitry model, whereby the amygdala is hyperactive due to poor top-down control from the anterior cingulate and ventromedial prefrontal cortices, has been supported by numerous experimental studies and meta-analyses. However, this model has not always been upheld by experimental data and clinical observations. In particular, many neuroimaging studies find that the amygdala fails to activate in response to negative stimuli in individuals with PTSD. Several technical and design issues may explain disparate results regarding amygdala reactivity in PTSD. However, biological and symptom-based factors emerge as possible mediators of amygdala function in PTSD, leading to the conclusion that symptoms of emotional disengagement and dissociation are associated with amygdala hyporeactivity, and symptoms of hypervigilance/hyperarousal and problems with fear conditioning and extinction are reflected by amygdala hyperactivity. Therefore, treatment of PTSD should take into account the nature of amygdala dysfunction in the individual to optimize treatment outcomes.",book:{id:"5485",slug:"the-amygdala-where-emotions-shape-perception-learning-and-memories",title:"The Amygdala",fullTitle:"The Amygdala - Where Emotions Shape Perception, Learning and Memories"},signatures:"Gina L. Forster, Raluca M. Simons and Lee A. Baugh",authors:[{id:"145620",title:"Dr.",name:"Gina",middleName:null,surname:"Forster",slug:"gina-forster",fullName:"Gina Forster"},{id:"195109",title:"Dr.",name:"Raluca",middleName:null,surname:"Simons",slug:"raluca-simons",fullName:"Raluca Simons"},{id:"195110",title:"Dr.",name:"Lee",middleName:null,surname:"Baugh",slug:"lee-baugh",fullName:"Lee Baugh"}]},{id:"55211",doi:"10.5772/intechopen.68618",title:"The Amygdala and Anxiety",slug:"the-amygdala-and-anxiety",totalDownloads:2984,totalCrossrefCites:4,totalDimensionsCites:8,abstract:"The amygdala has a central role in anxiety responses to stressful and arousing situations. Pharmacological and lesion studies of the basolateral, central, and medial subdivisions of the amygdala have shown that their activation induces anxiogenic effects, while their inactivation produces anxiolytic effects. Many neurotransmitters and stress mediators acting at these amygdalar nuclei can modulate the behavioral expression of anxiety. These mediators may be released from different brain regions in response to different types of stressors. The amygdala is in close relationship with several brain regions within the brain circuitry that orchestrates the expression of anxiety. Recent developments in optogenetics have begun to unveil details on how these areas interact.",book:{id:"5485",slug:"the-amygdala-where-emotions-shape-perception-learning-and-memories",title:"The Amygdala",fullTitle:"The Amygdala - Where Emotions Shape Perception, Learning and Memories"},signatures:"Sergio Linsambarth, Rodrigo Moraga-Amaro, Daisy Quintana-\nDonoso, Sebastian Rojas and Jimmy Stehberg",authors:[{id:"144923",title:"Dr.",name:"Jimmy",middleName:null,surname:"Stehberg",slug:"jimmy-stehberg",fullName:"Jimmy Stehberg"},{id:"194182",title:"Ph.D. Student",name:"Rodrigo",middleName:null,surname:"Moraga-Amaro",slug:"rodrigo-moraga-amaro",fullName:"Rodrigo Moraga-Amaro"},{id:"194183",title:"M.Sc.",name:"Sergio",middleName:null,surname:"Linsambarth",slug:"sergio-linsambarth",fullName:"Sergio Linsambarth"}]}],mostDownloadedChaptersLast30Days:[{id:"54675",title:"The Key Role of the Amygdala in Stress",slug:"the-key-role-of-the-amygdala-in-stress",totalDownloads:2940,totalCrossrefCites:3,totalDimensionsCites:4,abstract:"Several data highlighted that stress exposure is strongly associated with several psychiatric disorders. The amygdala, an area of the brain that contributes to emotional processing, has a pivotal role in psychiatric disorders and it has been demonstrated to be highly responsive to stressful events. Here we will review evidences indicating how the amygdala changes its functionality following exposure to stress and how this contributes to the onset of anxiety disorders.",book:{id:"5485",slug:"the-amygdala-where-emotions-shape-perception-learning-and-memories",title:"The Amygdala",fullTitle:"The Amygdala - Where Emotions Shape Perception, Learning and Memories"},signatures:"Diego Andolina and Antonella Borreca",authors:[{id:"190318",title:"Dr.",name:"Diego",middleName:null,surname:"Andolina",slug:"diego-andolina",fullName:"Diego Andolina"},{id:"192832",title:"Dr.",name:"Antonella",middleName:null,surname:"Borreca",slug:"antonella-borreca",fullName:"Antonella Borreca"}]},{id:"55211",title:"The Amygdala and Anxiety",slug:"the-amygdala-and-anxiety",totalDownloads:2985,totalCrossrefCites:4,totalDimensionsCites:8,abstract:"The amygdala has a central role in anxiety responses to stressful and arousing situations. Pharmacological and lesion studies of the basolateral, central, and medial subdivisions of the amygdala have shown that their activation induces anxiogenic effects, while their inactivation produces anxiolytic effects. Many neurotransmitters and stress mediators acting at these amygdalar nuclei can modulate the behavioral expression of anxiety. These mediators may be released from different brain regions in response to different types of stressors. The amygdala is in close relationship with several brain regions within the brain circuitry that orchestrates the expression of anxiety. Recent developments in optogenetics have begun to unveil details on how these areas interact.",book:{id:"5485",slug:"the-amygdala-where-emotions-shape-perception-learning-and-memories",title:"The Amygdala",fullTitle:"The Amygdala - Where Emotions Shape Perception, Learning and Memories"},signatures:"Sergio Linsambarth, Rodrigo Moraga-Amaro, Daisy Quintana-\nDonoso, Sebastian Rojas and Jimmy Stehberg",authors:[{id:"144923",title:"Dr.",name:"Jimmy",middleName:null,surname:"Stehberg",slug:"jimmy-stehberg",fullName:"Jimmy Stehberg"},{id:"194182",title:"Ph.D. Student",name:"Rodrigo",middleName:null,surname:"Moraga-Amaro",slug:"rodrigo-moraga-amaro",fullName:"Rodrigo Moraga-Amaro"},{id:"194183",title:"M.Sc.",name:"Sergio",middleName:null,surname:"Linsambarth",slug:"sergio-linsambarth",fullName:"Sergio Linsambarth"}]},{id:"32387",title:"The Mystery of P2X7 Ionotropic Receptor: From a Small Conductance Channel to a Large Conductance Channel",slug:"the-mystery-of-p2x7-receptor-from-a-small-channel-to-a-big-pore",totalDownloads:2420,totalCrossrefCites:0,totalDimensionsCites:0,abstract:null,book:{id:"1592",slug:"neuroscience-dealing-with-frontiers",title:"Neuroscience",fullTitle:"Neuroscience - Dealing With Frontiers"},signatures:"R.X. Faria, L.G.B. Ferreira and L.A. Alves",authors:[{id:"76663",title:"Prof.",name:"Luiz A.",middleName:null,surname:"Alves",slug:"luiz-a.-alves",fullName:"Luiz A. Alves"},{id:"76674",title:"Mr.",name:"Leonardo",middleName:null,surname:"Braga",slug:"leonardo-braga",fullName:"Leonardo Braga"},{id:"79615",title:"Dr.",name:"Robson",middleName:null,surname:"Faria",slug:"robson-faria",fullName:"Robson Faria"}]},{id:"32399",title:"Brain Energy Metabolism in Health and Disease",slug:"brain-energy-metabolism-in-health-and-disease",totalDownloads:9134,totalCrossrefCites:1,totalDimensionsCites:10,abstract:null,book:{id:"1592",slug:"neuroscience-dealing-with-frontiers",title:"Neuroscience",fullTitle:"Neuroscience - Dealing With Frontiers"},signatures:"Felipe A. Beltrán, Aníbal I. Acuña, María Paz Miró and Maite A. Castro",authors:[{id:"107041",title:"Dr.",name:"Maite A",middleName:null,surname:"Castro",slug:"maite-a-castro",fullName:"Maite A Castro"},{id:"109692",title:"Mr.",name:"Felipe A",middleName:null,surname:"Beltran",slug:"felipe-a-beltran",fullName:"Felipe A Beltran"},{id:"109695",title:"Mr.",name:"Aníbal",middleName:"I.",surname:"Acuña",slug:"anibal-acuna",fullName:"Aníbal Acuña"},{id:"109696",title:"Ms.",name:"Maria Paz",middleName:null,surname:"Miro",slug:"maria-paz-miro",fullName:"Maria Paz Miro"}]},{id:"54509",title:"The Contribution of the Amygdala to Reward-Related Learning and Extinction",slug:"the-contribution-of-the-amygdala-to-reward-related-learning-and-extinction",totalDownloads:1742,totalCrossrefCites:3,totalDimensionsCites:3,abstract:"There has been substantial research into the role of the amygdala in fear conditioning and extinction of conditioned fear. The role of the amygdala in appetitive conditioning is relatively less explored. Here, we will review research into the role of the amygdala in reward‐related learning. Research to date suggests that the basolateral and central amygdala are responsible for learning about distinct aspects of a reinforcing event. For example, the basolateral amygdala is essential for distinguishing and choosing between specific rewards based on the specific‐sensory properties of those rewards as well as updating the relative value of specific rewarding events. In contrast, the central amygdala is involved in encoding reinforcement more generally and for regulating motivational influences on responding. 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The combination of electronics and computer science with biology and medicine has improved patient diagnosis, reduced rehabilitation time, and helped to facilitate a better quality of life. Nowadays, all medical imaging devices, medical instruments, or new laboratory techniques result from the cooperation of specialists in various fields. The series of Biomedical Engineering books covers such areas of knowledge as chemistry, physics, electronics, medicine, and biology. 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Dr. Koprowski has authored more than a hundred research papers with dozens in impact factor (IF) journals and has authored or co-authored six books. Additionally, he is the author of several national and international patents in the field of biomedical devices and imaging. Since 2011, he has been a reviewer of grants and projects (including EU projects) in biomedical engineering.",institutionString:null,institution:{name:"University of Silesia",institutionURL:null,country:{name:"Poland"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:3,paginationItems:[{id:"7",title:"Bioinformatics and Medical Informatics",coverUrl:"https://cdn.intechopen.com/series_topics/covers/7.jpg",isOpenForSubmission:!0,editor:{id:"351533",title:"Dr.",name:"Slawomir",middleName:null,surname:"Wilczynski",slug:"slawomir-wilczynski",fullName:"Slawomir Wilczynski",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035U1loQAC/Profile_Picture_1630074514792",biography:"Professor Sławomir Wilczyński, Head of the Chair of Department of Basic Biomedical Sciences, Faculty of Pharmaceutical Sciences, Medical University of Silesia in Katowice, Poland. His research interests are focused on modern imaging methods used in medicine and pharmacy, including in particular hyperspectral imaging, dynamic thermovision analysis, high-resolution ultrasound, as well as other techniques such as EPR, NMR and hemispheric directional reflectance. Author of over 100 scientific works, patents and industrial designs. Expert of the Polish National Center for Research and Development, Member of the Investment Committee in the Bridge Alfa NCBiR program, expert of the Polish Ministry of Funds and Regional Policy, Polish Medical Research Agency. 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He completed a one-year Post-Doctoral Fellowship awarded by the DFAIT (Foreign Affairs and International Trade Canada) at the Institute of Biomedical Engineering of the University of New Brunswick (Canada) in 2010. Currently, he is Professor in the Faculty of Electrical Engineering (UFU). He has authored and co-authored more than 200 peer-reviewed publications in Biomedical Engineering. He has been a researcher of The National Council for Scientific and Technological Development (CNPq-Brazil) since 2009. He has served as an ad-hoc consultant for CNPq, CAPES (Coordination for the Improvement of Higher Education Personnel), FINEP (Brazilian Innovation Agency), and other funding bodies on several occasions. He was the Secretary of the Brazilian Society of Biomedical Engineering (SBEB) from 2015 to 2016, President of SBEB (2017-2018) and Vice-President of SBEB (2019-2020). He was the head of the undergraduate program in Biomedical Engineering of the Federal University of Uberlândia (2015 - June/2019) and the head of the Centre for Innovation and Technology Assessment in Health (NIATS/UFU) since 2010. He is the head of the Postgraduate Program in Biomedical Engineering (UFU, July/2019 - to date). He was the secretary of the Parkinson's Disease Association of Uberlândia (2018-2019). Dr. Andrade's primary area of research is focused towards getting information from the neuromuscular system to understand its strategies of organization, adaptation and controlling in the context of motor neuron diseases. 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Dr. Villarreal is the editor in chief and founder of the Revista de Ciencias Tecnológicas (RECIT) (https://recit.uabc.mx/) and is a member of several editorial and reviewer boards for numerous international journals. He has published more than thirty international papers and reviewed more than ninety-two manuscripts. 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His fields of interest are anterior segment disease, keratoconus, glaucoma, corneal dystrophies, and cataracts. His research topics include\nintraocular lens power calculation, eye modification induced by refractive surgery, glaucoma progression, and validation of new diagnostic devices in ophthalmology. \nHe has published more than 100 papers in international and Italian scientific journals, more than 60 in journals with impact factors, and chapters in international and Italian books. He has also edited two international books and authored more than 150 communications or posters for the most important international and Italian ophthalmology conferences.",institutionString:'University of Campania "Luigi Vanvitelli"',institution:{name:'University of Campania "Luigi Vanvitelli"',institutionURL:null,country:{name:"Italy"}}}]},{type:"book",id:"7560",title:"Non-Invasive Diagnostic Methods",subtitle:"Image Processing",coverURL:"https://cdn.intechopen.com/books/images_new/7560.jpg",slug:"non-invasive-diagnostic-methods-image-processing",publishedDate:"December 19th 2018",editedByType:"Edited by",bookSignature:"Mariusz Marzec and Robert Koprowski",hash:"d92fd8cf5a90a47f2b8a310837a5600e",volumeInSeries:3,fullTitle:"Non-Invasive Diagnostic Methods - Image Processing",editors:[{id:"253468",title:"Dr.",name:"Mariusz",middleName:null,surname:"Marzec",slug:"mariusz-marzec",fullName:"Mariusz Marzec",profilePictureURL:"https://mts.intechopen.com/storage/users/253468/images/system/253468.png",biography:"An assistant professor at Department of Biomedical Computer Systems, at Institute of Computer Science, Silesian University in Katowice. Scientific interests: computer analysis and processing of images, biomedical images, databases and programming languages. He is an author and co-author of scientific publications covering analysis and processing of biomedical images and development of database systems.",institutionString:"University of Silesia",institution:null}]},{type:"book",id:"6843",title:"Biomechanics",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/6843.jpg",slug:"biomechanics",publishedDate:"January 30th 2019",editedByType:"Edited by",bookSignature:"Hadi Mohammadi",hash:"85132976010be1d7f3dbd88662b785e5",volumeInSeries:4,fullTitle:"Biomechanics",editors:[{id:"212432",title:"Prof.",name:"Hadi",middleName:null,surname:"Mohammadi",slug:"hadi-mohammadi",fullName:"Hadi Mohammadi",profilePictureURL:"https://mts.intechopen.com/storage/users/212432/images/system/212432.jpeg",biography:"Dr. Hadi Mohammadi is a biomedical engineer with hands-on experience in the design and development of many engineering structures and medical devices through various projects that he has been involved in over the past twenty years. 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He has been reviewer for several publications of the Optical Society of America\\'s including Photonics Technology Letters and Applied Optics.\n\nPersonal Interests\nThese include motor cycling in a very relaxed manner and performing martial arts.",institutionString:null,institution:{name:"Charité",country:{name:"Germany"}}},{id:"341622",title:"Ph.D.",name:"Eduardo",middleName:null,surname:"Rojas Alvarez",slug:"eduardo-rojas-alvarez",fullName:"Eduardo Rojas Alvarez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/341622/images/15892_n.jpg",biography:null,institutionString:null,institution:{name:"University of Cuenca",country:{name:"Ecuador"}}},{id:"215610",title:"Prof.",name:"Muhammad",middleName:null,surname:"Sarfraz",slug:"muhammad-sarfraz",fullName:"Muhammad Sarfraz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/215610/images/system/215610.jpeg",biography:"Muhammad Sarfraz is a professor in the Department of Information Science, Kuwait University. His research interests include computer graphics, computer vision, image processing, machine learning, pattern recognition, soft computing, data science, intelligent systems, information technology, and information systems. Prof. Sarfraz has been a keynote/invited speaker on various platforms around the globe. He has advised various students for their MSc and Ph.D. theses. He has published more than 400 publications as books, journal articles, and conference papers. He is a member of various professional societies and a chair and member of the International Advisory Committees and Organizing Committees of various international conferences. Prof. Sarfraz is also an editor-in-chief and editor of various international journals.",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"32650",title:"Prof.",name:"Lukas",middleName:"Willem",surname:"Snyman",slug:"lukas-snyman",fullName:"Lukas Snyman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/32650/images/4136_n.jpg",biography:"Lukas Willem Snyman received his basic education at primary and high schools in South Africa, Eastern Cape. He enrolled at today's Nelson Metropolitan University and graduated from this university with a BSc in Physics and Mathematics, B.Sc Honors in Physics, MSc in Semiconductor Physics, and a Ph.D. in Semiconductor Physics in 1987. After his studies, he chose an academic career and devoted his energy to the teaching of physics to first, second, and third-year students. After positions as a lecturer at the University of Port Elizabeth, he accepted a position as Associate Professor at the University of Pretoria, South Africa.\r\n\r\nIn 1992, he motivates the concept of 'television and computer-based education” as means to reach large student numbers with only the best of teaching expertise and publishes an article on the concept in the SA Journal of Higher Education of 1993 (and later in 2003). The University of Pretoria subsequently approved a series of test projects on the concept with outreach to Mamelodi and Eerste Rust in 1993. In 1994, the University established a 'Unit for Telematic Education ' as a support section for multiple faculties at the University of Pretoria. In subsequent years, the concept of 'telematic education” subsequently becomes well established in academic circles in South Africa, grew in popularity, and is adopted by many universities and colleges throughout South Africa as a medium of enhancing education and training, as a method to reaching out to far out communities, and as a means to enhance study from the home environment.\r\n\r\nProfessor Snyman in subsequent years pursued research in semiconductor physics, semiconductor devices, microelectronics, and optoelectronics.\r\n\r\nIn 2000 he joined the TUT as a full professor. Here served for a period as head of the Department of Electronic Engineering. Here he makes contributions to solar energy development, microwave and optoelectronic device development, silicon photonics, as well as contributions to new mobile telecommunication systems and network planning in SA.\r\n\r\nCurrently, he teaches electronics and telecommunications at the TUT to audiences ranging from first-year students to Ph.D. level.\r\n\r\nFor his research in the field of 'Silicon Photonics” since 1990, he has published (as author and co-author) about thirty internationally reviewed articles in scientific journals, contributed to more than forty international conferences, about 25 South African provisional patents (as inventor and co-inventor), 8 PCT international patent applications until now. Of these, two USA patents applications, two European Patents, two Korean patents, and ten SA patents have been granted. A further 4 USA patents, 5 European patents, 3 Korean patents, 3 Chinese patents, and 3 Japanese patents are currently under consideration.\r\n\r\nRecently he has also published an extensive scholarly chapter in an internet open access book on 'Integrating Microphotonic Systems and MOEMS into standard Silicon CMOS Integrated circuitry”.\r\n\r\nFurthermore, Professor Snyman recently steered a new initiative at the TUT by introducing a 'Laboratory for Innovative Electronic Systems ' at the Department of Electrical Engineering. The model of this laboratory or center is to primarily combine outputs as achieved by high-level research with lower-level system development and entrepreneurship in a technical university environment. Students are allocated to projects at different levels with PhDs and Master students allocated to the generation of new knowledge and new technologies, while students at the diploma and Baccalaureus level are allocated to electronic systems development with a direct and a near application for application in industry or the commercial and public sectors in South Africa.\r\n\r\nProfessor Snyman received the WIRSAM Award of 1983 and the WIRSAM Award in 1985 in South Africa for best research papers by a young scientist at two international conferences on electron microscopy in South Africa. He subsequently received the SA Microelectronics Award for the best dissertation emanating from studies executed at a South African university in the field of Physics and Microelectronics in South Africa in 1987. In October of 2011, Professor Snyman received the prestigious Institutional Award for 'Innovator of the Year” for 2010 at the Tshwane University of Technology, South Africa. This award was based on the number of patents recognized and granted by local and international institutions as well as for his contributions concerning innovation at the TUT.",institutionString:null,institution:{name:"University of South Africa",country:{name:"South Africa"}}},{id:"317279",title:"Mr.",name:"Ali",middleName:"Usama",surname:"Syed",slug:"ali-syed",fullName:"Ali Syed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/317279/images/16024_n.png",biography:"A creative, talented, and innovative young professional who is dedicated, well organized, and capable research fellow with two years of experience in graduate-level research, published in engineering journals and book, with related expertise in Bio-robotics, equally passionate about the aesthetics of the mechanical and electronic system, obtained expertise in the use of MS Office, MATLAB, SolidWorks, LabVIEW, Proteus, Fusion 360, having a grasp on python, C++ and assembly language, possess proven ability in acquiring research grants, previous appointments with social and educational societies with experience in administration, current affiliations with IEEE and Web of Science, a confident presenter at conferences and teacher in classrooms, able to explain complex information to audiences of all levels.",institutionString:null,institution:{name:"Air University",country:{name:"Pakistan"}}},{id:"75526",title:"Ph.D.",name:"Zihni Onur",middleName:null,surname:"Uygun",slug:"zihni-onur-uygun",fullName:"Zihni Onur Uygun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/75526/images/12_n.jpg",biography:"My undergraduate education and my Master of Science educations at Ege University and at Çanakkale Onsekiz Mart University have given me a firm foundation in Biochemistry, Analytical Chemistry, Biosensors, Bioelectronics, Physical Chemistry and Medicine. After obtaining my degree as a MSc in analytical chemistry, I started working as a research assistant in Ege University Medical Faculty in 2014. In parallel, I enrolled to the MSc program at the Department of Medical Biochemistry at Ege University to gain deeper knowledge on medical and biochemical sciences as well as clinical chemistry in 2014. In my PhD I deeply researched on biosensors and bioelectronics and finished in 2020. Now I have eleven SCI-Expanded Index published papers, 6 international book chapters, referee assignments for different SCIE journals, one international patent pending, several international awards, projects and bursaries. In parallel to my research assistant position at Ege University Medical Faculty, Department of Medical Biochemistry, in April 2016, I also founded a Start-Up Company (Denosens Biotechnology LTD) by the support of The Scientific and Technological Research Council of Turkey. Currently, I am also working as a CEO in Denosens Biotechnology. The main purposes of the company, which carries out R&D as a research center, are to develop new generation biosensors and sensors for both point-of-care diagnostics; such as glucose, lactate, cholesterol and cancer biomarker detections. My specific experimental and instrumental skills are Biochemistry, Biosensor, Analytical Chemistry, Electrochemistry, Mobile phone based point-of-care diagnostic device, POCTs and Patient interface designs, HPLC, Tandem Mass Spectrometry, Spectrophotometry, ELISA.",institutionString:null,institution:{name:"Ege University",country:{name:"Turkey"}}},{id:"267434",title:"Dr.",name:"Rohit",middleName:null,surname:"Raja",slug:"rohit-raja",fullName:"Rohit Raja",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/267434/images/system/267434.jpg",biography:"Dr. Rohit Raja received Ph.D. in Computer Science and Engineering from Dr. CVRAMAN University in 2016. His main research interest includes Face recognition and Identification, Digital Image Processing, Signal Processing, and Networking. Presently he is working as Associate Professor in IT Department, Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur (CG), India. He has authored several Journal and Conference Papers. He has good Academics & Research experience in various areas of CSE and IT. He has filed and successfully published 27 Patents. He has received many time invitations to be a Guest at IEEE Conferences. He has published 100 research papers in various International/National Journals (including IEEE, Springer, etc.) and Proceedings of the reputed International/ National Conferences (including Springer and IEEE). He has been nominated to the board of editors/reviewers of many peer-reviewed and refereed Journals (including IEEE, Springer).",institutionString:"Guru Ghasidas Vishwavidyalaya",institution:{name:"Guru Ghasidas Vishwavidyalaya",country:{name:"India"}}},{id:"246502",title:"Dr.",name:"Jaya T.",middleName:"T",surname:"Varkey",slug:"jaya-t.-varkey",fullName:"Jaya T. Varkey",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246502/images/11160_n.jpg",biography:"Jaya T. Varkey, PhD, graduated with a degree in Chemistry from Cochin University of Science and Technology, Kerala, India. She obtained a PhD in Chemistry from the School of Chemical Sciences, Mahatma Gandhi University, Kerala, India, and completed a post-doctoral fellowship at the University of Minnesota, USA. She is a research guide at Mahatma Gandhi University and Associate Professor in Chemistry, St. Teresa’s College, Kochi, Kerala, India.\nDr. Varkey received a National Young Scientist award from the Indian Science Congress (1995), a UGC Research award (2016–2018), an Indian National Science Academy (INSA) Visiting Scientist award (2018–2019), and a Best Innovative Faculty award from the All India Association for Christian Higher Education (AIACHE) (2019). She Hashas received the Sr. Mary Cecil prize for best research paper three times. She was also awarded a start-up to develop a tea bag water filter. \nDr. Varkey has published two international books and twenty-seven international journal publications. She is an editorial board member for five international journals.",institutionString:"St. Teresa’s College",institution:null},{id:"250668",title:"Dr.",name:"Ali",middleName:null,surname:"Nabipour Chakoli",slug:"ali-nabipour-chakoli",fullName:"Ali Nabipour Chakoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/250668/images/system/250668.jpg",biography:"Academic Qualification:\r\n•\tPhD in Materials Physics and Chemistry, From: Sep. 2006, to: Sep. 2010, School of Materials Science and Engineering, Harbin Institute of Technology, Thesis: Structure and Shape Memory Effect of Functionalized MWCNTs/poly (L-lactide-co-ε-caprolactone) Nanocomposites. Supervisor: Prof. Wei Cai,\r\n•\tM.Sc in Applied Physics, From: 1996, to: 1998, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Determination of Boron in Micro alloy Steels with solid state nuclear track detectors by neutron induced auto radiography, Supervisors: Dr. M. Hosseini Ashrafi and Dr. A. Hosseini.\r\n•\tB.Sc. in Applied Physics, From: 1991, to: 1996, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Design of shielding for Am-Be neutron sources for In Vivo neutron activation analysis, Supervisor: Dr. M. Hosseini Ashrafi.\r\n\r\nResearch Experiences:\r\n1.\tNanomaterials, Carbon Nanotubes, Graphene: Synthesis, Functionalization and Characterization,\r\n2.\tMWCNTs/Polymer Composites: Fabrication and Characterization, \r\n3.\tShape Memory Polymers, Biodegradable Polymers, ORC, Collagen,\r\n4.\tMaterials Analysis and Characterizations: TEM, SEM, XPS, FT-IR, Raman, DSC, DMA, TGA, XRD, GPC, Fluoroscopy, \r\n5.\tInteraction of Radiation with Mater, Nuclear Safety and Security, NDT(RT),\r\n6.\tRadiation Detectors, Calibration (SSDL),\r\n7.\tCompleted IAEA e-learning Courses:\r\nNuclear Security (15 Modules),\r\nNuclear Safety:\r\nTSA 2: Regulatory Protection in Occupational Exposure,\r\nTips & Tricks: Radiation Protection in Radiography,\r\nSafety and Quality in Radiotherapy,\r\nCourse on Sealed Radioactive Sources,\r\nCourse on Fundamentals of Environmental Remediation,\r\nCourse on Planning for Environmental Remediation,\r\nKnowledge Management Orientation Course,\r\nFood Irradiation - Technology, Applications and Good Practices,\r\nEmployment:\r\nFrom 2010 to now: Academic staff, Nuclear Science and Technology Research Institute, Kargar Shomali, Tehran, Iran, P.O. Box: 14395-836.\r\nFrom 1997 to 2006: Expert of Materials Analysis and Characterization. Research Center of Agriculture and Medicine. Rajaeeshahr, Karaj, Iran, P. O. Box: 31585-498.",institutionString:"Atomic Energy Organization of Iran",institution:{name:"Atomic Energy Organization of Iran",country:{name:"Iran"}}},{id:"248279",title:"Dr.",name:"Monika",middleName:"Elzbieta",surname:"Machoy",slug:"monika-machoy",fullName:"Monika Machoy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248279/images/system/248279.jpeg",biography:"Monika Elżbieta Machoy, MD, graduated with distinction from the Faculty of Medicine and Dentistry at the Pomeranian Medical University in 2009, defended her PhD thesis with summa cum laude in 2016 and is currently employed as a researcher at the Department of Orthodontics of the Pomeranian Medical University. She expanded her professional knowledge during a one-year scholarship program at the Ernst Moritz Arndt University in Greifswald, Germany and during a three-year internship at the Technical University in Dresden, Germany. She has been a speaker at numerous orthodontic conferences, among others, American Association of Orthodontics, European Orthodontic Symposium and numerous conferences of the Polish Orthodontic Society. She conducts research focusing on the effect of orthodontic treatment on dental and periodontal tissues and the causes of pain in orthodontic patients.",institutionString:"Pomeranian Medical University",institution:{name:"Pomeranian Medical University",country:{name:"Poland"}}},{id:"252743",title:"Prof.",name:"Aswini",middleName:"Kumar",surname:"Kar",slug:"aswini-kar",fullName:"Aswini Kar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252743/images/10381_n.jpg",biography:"uploaded in cv",institutionString:null,institution:{name:"KIIT University",country:{name:"India"}}},{id:"204256",title:"Dr.",name:"Anil",middleName:"Kumar",surname:"Kumar Sahu",slug:"anil-kumar-sahu",fullName:"Anil Kumar Sahu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204256/images/14201_n.jpg",biography:"I have nearly 11 years of research and teaching experience. I have done my master degree from University Institute of Pharmacy, Pt. Ravi Shankar Shukla University, Raipur, Chhattisgarh India. I have published 16 review and research articles in international and national journals and published 4 chapters in IntechOpen, the world’s leading publisher of Open access books. I have presented many papers at national and international conferences. I have received research award from Indian Drug Manufacturers Association in year 2015. My research interest extends from novel lymphatic drug delivery systems, oral delivery system for herbal bioactive to formulation optimization.",institutionString:null,institution:{name:"Chhattisgarh Swami Vivekanand Technical University",country:{name:"India"}}},{id:"253468",title:"Dr.",name:"Mariusz",middleName:null,surname:"Marzec",slug:"mariusz-marzec",fullName:"Mariusz Marzec",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/253468/images/system/253468.png",biography:"An assistant professor at Department of Biomedical Computer Systems, at Institute of Computer Science, Silesian University in Katowice. Scientific interests: computer analysis and processing of images, biomedical images, databases and programming languages. He is an author and co-author of scientific publications covering analysis and processing of biomedical images and development of database systems.",institutionString:"University of Silesia",institution:null},{id:"212432",title:"Prof.",name:"Hadi",middleName:null,surname:"Mohammadi",slug:"hadi-mohammadi",fullName:"Hadi Mohammadi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/212432/images/system/212432.jpeg",biography:"Dr. Hadi Mohammadi is a biomedical engineer with hands-on experience in the design and development of many engineering structures and medical devices through various projects that he has been involved in over the past twenty years. Dr. Mohammadi received his BSc. and MSc. degrees in Mechanical Engineering from Sharif University of Technology, Tehran, Iran, and his PhD. degree in Biomedical Engineering (biomaterials) from the University of Western Ontario. He was a postdoctoral trainee for almost four years at University of Calgary and Harvard Medical School. He is an industry innovator having created the technology to produce lifelike synthetic platforms that can be used for the simulation of almost all cardiovascular reconstructive surgeries. He’s been heavily involved in the design and development of cardiovascular devices and technology for the past 10 years. He is currently an Assistant Professor with the University of British Colombia, Canada.",institutionString:"University of British Columbia",institution:{name:"University of British Columbia",country:{name:"Canada"}}},{id:"254463",title:"Prof.",name:"Haisheng",middleName:null,surname:"Yang",slug:"haisheng-yang",fullName:"Haisheng Yang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/254463/images/system/254463.jpeg",biography:"Haisheng Yang, Ph.D., Professor and Director of the Department of Biomedical Engineering, College of Life Science and Bioengineering, Beijing University of Technology. He received his Ph.D. degree in Mechanics/Biomechanics from Harbin Institute of Technology (jointly with University of California, Berkeley). Afterwards, he worked as a Postdoctoral Research Associate in the Purdue Musculoskeletal Biology and Mechanics Lab at the Department of Basic Medical Sciences, Purdue University, USA. He also conducted research in the Research Centre of Shriners Hospitals for Children-Canada at McGill University, Canada. Dr. Yang has over 10 years research experience in orthopaedic biomechanics and mechanobiology of bone adaptation and regeneration. He earned an award from Beijing Overseas Talents Aggregation program in 2017 and serves as Beijing Distinguished Professor.",institutionString:null,institution:{name:"Beijing University of Technology",country:{name:"China"}}},{id:"89721",title:"Dr.",name:"Mehmet",middleName:"Cuneyt",surname:"Ozmen",slug:"mehmet-ozmen",fullName:"Mehmet Ozmen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/89721/images/7289_n.jpg",biography:null,institutionString:null,institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"242893",title:"Ph.D. Student",name:"Joaquim",middleName:null,surname:"De Moura",slug:"joaquim-de-moura",fullName:"Joaquim De Moura",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/242893/images/7133_n.jpg",biography:"Joaquim de Moura received his degree in Computer Engineering in 2014 from the University of A Coruña (Spain). In 2016, he received his M.Sc degree in Computer Engineering from the same university. He is currently pursuing his Ph.D degree in Computer Science in a collaborative project between ophthalmology centers in Galicia and the University of A Coruña. His research interests include computer vision, machine learning algorithms and analysis and medical imaging processing of various kinds.",institutionString:null,institution:{name:"University of A Coruña",country:{name:"Spain"}}},{id:"294334",title:"B.Sc.",name:"Marc",middleName:null,surname:"Bruggeman",slug:"marc-bruggeman",fullName:"Marc Bruggeman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/294334/images/8242_n.jpg",biography:"Chemical engineer graduate, with a passion for material science and specific interest in polymers - their near infinite applications intrigue me. \n\nI plan to continue my scientific career in the field of polymeric biomaterials as I am fascinated by intelligent, bioactive and biomimetic materials for use in both consumer and medical applications.",institutionString:null,institution:null},{id:"255757",title:"Dr.",name:"Igor",middleName:"Victorovich",surname:"Lakhno",slug:"igor-lakhno",fullName:"Igor Lakhno",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255757/images/system/255757.jpg",biography:"Igor Victorovich Lakhno was born in 1971 in Kharkiv (Ukraine). \nMD – 1994, Kharkiv National Medical Univesity.\nOb&Gyn; – 1997, master courses in Kharkiv Medical Academy of Postgraduate Education.\nPh.D. – 1999, Kharkiv National Medical Univesity.\nDSC – 2019, PL Shupik National Academy of Postgraduate Education \nProfessor – 2021, Department of Obstetrics and Gynecology of VN Karazin Kharkiv National University\nHead of Department – 2021, Department of Perinatology, Obstetrics and gynecology of Kharkiv Medical Academy of Postgraduate Education\nIgor Lakhno has been graduated from international training courses on reproductive medicine and family planning held at Debrecen University (Hungary) in 1997. Since 1998 Lakhno Igor has worked as an associate professor in the department of obstetrics and gynecology of VN Karazin National University and an associate professor of the perinatology, obstetrics, and gynecology department of Kharkiv Medical Academy of Postgraduate Education. Since June 2019 he’s been a professor in the department of obstetrics and gynecology of VN Karazin National University and a professor of the perinatology, obstetrics, and gynecology department. He’s affiliated with Kharkiv Medical Academy of Postgraduate Education as a Head of Department from November 2021. Igor Lakhno has participated in several international projects on fetal non-invasive electrocardiography (with Dr. J. A. Behar (Technion), Prof. D. Hoyer (Jena University), and José Alejandro Díaz Méndez (National Institute of Astrophysics, Optics, and Electronics, Mexico). He’s an author of about 200 printed works and there are 31 of them in Scopus or Web of Science databases. Igor Lakhno is a member of the Editorial Board of Reproductive Health of Woman, Emergency Medicine, and Technology Transfer Innovative Solutions in Medicine (Estonia). He is a medical Editor of “Z turbotoyu pro zhinku”. Igor Lakhno is a reviewer of the Journal of Obstetrics and Gynaecology (Taylor and Francis), British Journal of Obstetrics and Gynecology (Wiley), Informatics in Medicine Unlocked (Elsevier), The Journal of Obstetrics and Gynecology Research (Wiley), Endocrine, Metabolic & Immune Disorders-Drug Targets (Bentham Open), The Open Biomedical Engineering Journal (Bentham Open), etc. He’s defended a dissertation for a DSc degree “Pre-eclampsia: prediction, prevention, and treatment”. Three years ago Igor Lakhno has participated in a training course on innovative technologies in medical education at Lublin Medical University (Poland). Lakhno Igor has participated as a speaker in several international conferences and congresses (International Conference on Biological Oscillations April 10th-14th 2016, Lancaster, UK, The 9th conference of the European Study Group on Cardiovascular Oscillations). His main scientific interests: are obstetrics, women’s health, fetal medicine, and cardiovascular medicine. \nIgor Lakhno is a consultant at Kharkiv municipal perinatal center. He’s graduated from training courses on endoscopy in gynecology. He has 28 years of practical experience in the field.",institutionString:null,institution:null},{id:"244950",title:"Dr.",name:"Salvatore",middleName:null,surname:"Di Lauro",slug:"salvatore-di-lauro",fullName:"Salvatore Di Lauro",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0030O00002bSF1HQAW/ProfilePicture%202021-12-20%2014%3A54%3A14.482",biography:"Name:\n\tSALVATORE DI LAURO\nAddress:\n\tHospital Clínico Universitario Valladolid\nAvda Ramón y Cajal 3\n47005, Valladolid\nSpain\nPhone number: \nFax\nE-mail:\n\t+34 983420000 ext 292\n+34 983420084\nsadilauro@live.it\nDate and place of Birth:\nID Number\nMedical Licence \nLanguages\t09-05-1985. Villaricca (Italy)\n\nY1281863H\n474707061\nItalian (native language)\nSpanish (read, written, spoken)\nEnglish (read, written, spoken)\nPortuguese (read, spoken)\nFrench (read)\n\t\t\nCurrent position (title and company)\tDate (Year)\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. Private practise.\t2017-today\n\n2019-today\n\t\n\t\nEducation (High school, university and postgraduate training > 3 months)\tDate (Year)\nDegree in Medicine and Surgery. University of Neaples 'Federico II”\nResident in Opthalmology. Hospital Clinico Universitario Valladolid\nMaster in Vitreo-Retina. IOBA. University of Valladolid\nFellow of the European Board of Ophthalmology. Paris\nMaster in Research in Ophthalmology. University of Valladolid\t2003-2009\n2012-2016\n2016-2017\n2016\n2012-2013\n\t\nEmployments (company and positions)\tDate (Year)\nResident in Ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl.\nFellow in Vitreo-Retina. IOBA. University of Valladolid\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. \n\t2012-2016\n2016-2017\n2017-today\n\n2019-Today\n\n\n\t\nClinical Research Experience (tasks and role)\tDate (Year)\nAssociated investigator\n\n' FIS PI20/00740: DESARROLLO DE UNA CALCULADORA DE RIESGO DE\nAPARICION DE RETINOPATIA DIABETICA BASADA EN TECNICAS DE IMAGEN MULTIMODAL EN PACIENTES DIABETICOS TIPO 1. Grant by: Ministerio de Ciencia e Innovacion \n\n' (BIO/VA23/14) Estudio clínico multicéntrico y prospectivo para validar dos\nbiomarcadores ubicados en los genes p53 y MDM2 en la predicción de los resultados funcionales de la cirugía del desprendimiento de retina regmatógeno. Grant by: Gerencia Regional de Salud de la Junta de Castilla y León.\n' Estudio multicéntrico, aleatorizado, con enmascaramiento doble, en 2 grupos\nparalelos y de 52 semanas de duración para comparar la eficacia, seguridad e inmunogenicidad de SOK583A1 respecto a Eylea® en pacientes con degeneración macular neovascular asociada a la edad' (CSOK583A12301; N.EUDRA: 2019-004838-41; FASE III). Grant by Hexal AG\n\n' Estudio de fase III, aleatorizado, doble ciego, con grupos paralelos, multicéntrico para comparar la eficacia y la seguridad de QL1205 frente a Lucentis® en pacientes con degeneración macular neovascular asociada a la edad. (EUDRACT: 2018-004486-13). Grant by Qilu Pharmaceutical Co\n\n' Estudio NEUTON: Ensayo clinico en fase IV para evaluar la eficacia de aflibercept en pacientes Naive con Edema MacUlar secundario a Oclusion de Vena CenTral de la Retina (OVCR) en regimen de tratamientO iNdividualizado Treat and Extend (TAE)”, (2014-000975-21). Grant by Fundacion Retinaplus\n\n' Evaluación de la seguridad y bioactividad de anillos de tensión capsular en conejo. Proyecto Procusens. Grant by AJL, S.A.\n\n'Estudio epidemiológico, prospectivo, multicéntrico y abierto\\npara valorar la frecuencia de la conjuntivitis adenovírica diagnosticada mediante el test AdenoPlus®\\nTest en pacientes enfermos de conjuntivitis aguda”\\n. National, multicenter study. Grant by: NICOX.\n\nEuropean multicentric trial: 'Evaluation of clinical outcomes following the use of Systane Hydration in patients with dry eye”. Study Phase 4. Grant by: Alcon Labs'\n\nVLPs Injection and Activation in a Rabbit Model of Uveal Melanoma. Grant by Aura Bioscience\n\nUpdating and characterization of a rabbit model of uveal melanoma. Grant by Aura Bioscience\n\nEnsayo clínico en fase IV para evaluar las variantes genéticas de la vía del VEGF como biomarcadores de eficacia del tratamiento con aflibercept en pacientes con degeneración macular asociada a la edad (DMAE) neovascular. Estudio BIOIMAGE. IMO-AFLI-2013-01\n\nEstudio In-Eye:Ensayo clínico en fase IV, abierto, aleatorizado, de 2 brazos,\nmulticçentrico y de 12 meses de duración, para evaluar la eficacia y seguridad de un régimen de PRN flexible individualizado de 'esperar y extender' versus un régimen PRN según criterios de estabilización mediante evaluaciones mensuales de inyecciones intravítreas de ranibizumab 0,5 mg en pacientes naive con neovascularización coriodea secunaria a la degeneración macular relacionada con la edad. CP: CRFB002AES03T\n\nTREND: Estudio Fase IIIb multicéntrico, randomizado, de 12 meses de\nseguimiento con evaluador de la agudeza visual enmascarado, para evaluar la eficacia y la seguridad de ranibizumab 0.5mg en un régimen de tratar y extender comparado con un régimen mensual, en pacientes con degeneración macular neovascular asociada a la edad. CP: CRFB002A2411 Código Eudra CT:\n2013-002626-23\n\n\n\nPublications\t\n\n2021\n\n\n\n\n2015\n\n\n\n\n2021\n\n\n\n\n\n2021\n\n\n\n\n2015\n\n\n\n\n2015\n\n\n2014\n\n\n\n\n2015-16\n\n\n\n2015\n\n\n2014\n\n\n2014\n\n\n\n\n2014\n\n\n\n\n\n\n\n2014\n\nJose Carlos Pastor; Jimena Rojas; Salvador Pastor-Idoate; Salvatore Di Lauro; Lucia Gonzalez-Buendia; Santiago Delgado-Tirado. Proliferative vitreoretinopathy: A new concept of disease pathogenesis and practical\nconsequences. Progress in Retinal and Eye Research. 51, pp. 125 - 155. 03/2016. DOI: 10.1016/j.preteyeres.2015.07.005\n\n\nLabrador-Velandia S; Alonso-Alonso ML; Di Lauro S; García-Gutierrez MT; Srivastava GK; Pastor JC; Fernandez-Bueno I. Mesenchymal stem cells provide paracrine neuroprotective resources that delay degeneration of co-cultured organotypic neuroretinal cultures.Experimental Eye Research. 185, 17/05/2019. DOI: 10.1016/j.exer.2019.05.011\n\nSalvatore Di Lauro; Maria Teresa Garcia Gutierrez; Ivan Fernandez Bueno. Quantification of pigment epithelium-derived factor (PEDF) in an ex vivo coculture of retinal pigment epithelium cells and neuroretina.\nJournal of Allbiosolution. 2019. ISSN 2605-3535\n\nSonia Labrador Velandia; Salvatore Di Lauro; Alonso-Alonso ML; Tabera Bartolomé S; Srivastava GK; Pastor JC; Fernandez-Bueno I. Biocompatibility of intravitreal injection of human mesenchymal stem cells in immunocompetent rabbits. Graefe's archive for clinical and experimental ophthalmology. 256 - 1, pp. 125 - 134. 01/2018. DOI: 10.1007/s00417-017-3842-3\n\n\nSalvatore Di Lauro, David Rodriguez-Crespo, Manuel J Gayoso, Maria T Garcia-Gutierrez, J Carlos Pastor, Girish K Srivastava, Ivan Fernandez-Bueno. A novel coculture model of porcine central neuroretina explants and retinal pigment epithelium cells. Molecular Vision. 2016 - 22, pp. 243 - 253. 01/2016.\n\nSalvatore Di Lauro. Classifications for Proliferative Vitreoretinopathy ({PVR}): An Analysis of Their Use in Publications over the Last 15 Years. Journal of Ophthalmology. 2016, pp. 1 - 6. 01/2016. DOI: 10.1155/2016/7807596\n\nSalvatore Di Lauro; Rosa Maria Coco; Rosa Maria Sanabria; Enrique Rodriguez de la Rua; Jose Carlos Pastor. Loss of Visual Acuity after Successful Surgery for Macula-On Rhegmatogenous Retinal Detachment in a Prospective Multicentre Study. Journal of Ophthalmology. 2015:821864, 2015. DOI: 10.1155/2015/821864\n\nIvan Fernandez-Bueno; Salvatore Di Lauro; Ivan Alvarez; Jose Carlos Lopez; Maria Teresa Garcia-Gutierrez; Itziar Fernandez; Eva Larra; Jose Carlos Pastor. Safety and Biocompatibility of a New High-Density Polyethylene-Based\nSpherical Integrated Porous Orbital Implant: An Experimental Study in Rabbits. Journal of Ophthalmology. 2015:904096, 2015. DOI: 10.1155/2015/904096\n\nPastor JC; Pastor-Idoate S; Rodríguez-Hernandez I; Rojas J; Fernandez I; Gonzalez-Buendia L; Di Lauro S; Gonzalez-Sarmiento R. Genetics of PVR and RD. Ophthalmologica. 232 - Suppl 1, pp. 28 - 29. 2014\n\nRodriguez-Crespo D; Di Lauro S; Singh AK; Garcia-Gutierrez MT; Garrosa M; Pastor JC; Fernandez-Bueno I; Srivastava GK. Triple-layered mixed co-culture model of RPE cells with neuroretina for evaluating the neuroprotective effects of adipose-MSCs. Cell Tissue Res. 358 - 3, pp. 705 - 716. 2014.\nDOI: 10.1007/s00441-014-1987-5\n\nCarlo De Werra; Salvatore Condurro; Salvatore Tramontano; Mario Perone; Ivana Donzelli; Salvatore Di Lauro; Massimo Di Giuseppe; Rosa Di Micco; Annalisa Pascariello; Antonio Pastore; Giorgio Diamantis; Giuseppe Galloro. Hydatid disease of the liver: thirty years of surgical experience.Chirurgia italiana. 59 - 5, pp. 611 - 636.\n(Italia): 2007. ISSN 0009-4773\n\nChapters in books\n\t\n' Salvador Pastor Idoate; Salvatore Di Lauro; Jose Carlos Pastor Jimeno. PVR: Pathogenesis, Histopathology and Classification. Proliferative Vitreoretinopathy with Small Gauge Vitrectomy. Springer, 2018. ISBN 978-3-319-78445-8\nDOI: 10.1007/978-3-319-78446-5_2. \n\n' Salvatore Di Lauro; Maria Isabel Lopez Galvez. Quistes vítreos en una mujer joven. Problemas diagnósticos en patología retinocoroidea. Sociedad Española de Retina-Vitreo. 2018.\n\n' Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor Jimeno. iOCT in PVR management. OCT Applications in Opthalmology. pp. 1 - 8. INTECH, 2018. DOI: 10.5772/intechopen.78774.\n\n' Rosa Coco Martin; Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor. amponadores, manipuladores y tinciones en la cirugía del traumatismo ocular.Trauma Ocular. Ponencia de la SEO 2018..\n\n' LOPEZ GALVEZ; DI LAURO; CRESPO. OCT angiografia y complicaciones retinianas de la diabetes. PONENCIA SEO 2021, CAPITULO 20. (España): 2021.\n\n' Múltiples desprendimientos neurosensoriales bilaterales en paciente joven. Enfermedades Degenerativas De Retina Y Coroides. SERV 04/2016. \n' González-Buendía L; Di Lauro S; Pastor-Idoate S; Pastor Jimeno JC. Vitreorretinopatía proliferante (VRP) e inflamación: LA INFLAMACIÓN in «INMUNOMODULADORES Y ANTIINFLAMATORIOS: MÁS ALLÁ DE LOS CORTICOIDES. 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