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Millis",coverURL:"https://cdn.intechopen.com/books/images_new/358.jpg",editedByType:"Edited by",editors:[{id:"45295",title:"PhD.",name:"Richard",surname:"Millis",slug:"richard-millis",fullName:"Richard Millis"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1291",title:"Advances in Electrocardiograms",subtitle:"Clinical Applications",isOpenForSubmission:!1,hash:"956bc1bdc0de1de4908abbee641a17aa",slug:"advances-in-electrocardiograms-clinical-applications",bookSignature:"Richard M. Millis",coverURL:"https://cdn.intechopen.com/books/images_new/1291.jpg",editedByType:"Edited by",editors:[{id:"45295",title:"PhD.",name:"Richard",surname:"Millis",slug:"richard-millis",fullName:"Richard Millis"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],publishedBooksByAuthor:[]},onlineFirst:{chapter:{type:"chapter",id:"78485",title:"Hemodynamic Perspectives in Anemia",doi:"10.5772/intechopen.99725",slug:"hemodynamic-perspectives-in-anemia",body:'Anemia in critically ill patients is almost inevitable. The etiology of this can be varied, including overt blood loss, bone marrow suppression, functional iron deficiency, and decreased erythropoiesis [1]. Reports indicate that more than 95% of patients in an ICU are anemic by Day 8. Interventions such as scheduled daily phlebotomies lead to about 70-100 cc/day blood loss, while body turnover is about 15-20 cc/day. Little do we realize that this “anemia of chronic investigation” can lead up to 1/3 of transfusions when considering the current transfusion threshold practice of hemoglobin (Hb) less than 7 g/dL [2]. However, with numerous methods currently available to assess transfusions’ physiological response, treating an arbitrary number is not the most refined approach. Parameters such as oxygen delivery (DO2), oxygen consumption (VO2), oxygen extraction ratio (O2ER), and cardiac output are of paramount importance in the decision to transfuse RBCs.
This chapter aims to discuss the physiology of oxygen delivery, the pathophysiology of lung injury related to volume overload, and transfusion-related injury. Ultimately, we would like to demonstrate how employing a simple physiologic algorithm using parameters such as stroke volume, and stroke volume variability can lead to better care in this population.
The trigger to order blood products in the medical ICU is often a reflex action. In critically ill patients, the goal of transfusion in a volume replenished patient should aim to improve oxygen delivery and thereby accomplish the end goal of improving oxygen uptake in tissues. There is much evidence regarding liberal vs. restrictive transfusion limits in various subsets of patients. Vastly discussed strategy being restrictive transfusion (less than 7 g/dL) vs. liberal transfusion goals (9-10 g/dL). We can all agree that 7 g/dL is presently the customary number across many diseases. The TRICC trial randomized 838 critically ill patients to liberal (goal hemoglobin 10–12 g/dL) versus restrictive (goal hemoglobin 7–9 g/dL) transfusion strategies observed no benefit to liberal transfusion. However, the study almost achieved (p=0.11) statistical significance for finding increased mortality in patients randomized to liberal transfusion. This trial showed that there was no 30-day mortality difference between restrictive strategy vs. liberal strategy. Still, it showed harm in the subset of younger patients with lower APACHE scores and clinically significant cardiac disease [3]. Current data suggests that restrictive strategy in critically ill patients decreases the number of transfusion reactions, length of stay, and mortality [4]. Various studies focusing on patients with ARDS, trauma, and sepsis have shown that tissue oxygenation and extraction does not improve with transfusion alone. This disparity is attributable to poor flow characteristics, high O2 affinity secondary to reduced 2,3 DPG concentration in transfused blood and increased viscosity affecting functional capillary diameter. While large multicenter trials recently have shown a higher threshold to transfuse is beneficial or at least non-injurious, it is prudent to focus on the physiological response a patient may have to blood transfusion.
Does it make a difference? Each gram of Hemoglobin can carry 1.34 cc of O2, with each molecule 100% saturated as it enters systemic circulation.
DO2 is derived from the following (Eq. (1)):
VO2 is calculated by the difference between oxygen content in arterial blood and venous blood (Eq. (4)).
Hence,
The fundamental goal of RBC transfusion is to improve oxygen content and to improve tissue oxygenation and delivery. While decreasing hemoglobin concentration can lead to critical oxygen content and delivery, this can be compensated by improving cardiac output and maintaining a euvolemic status.
VO2 calculated with this equation is called the reverse Fick method. With an increase in oxygen demand, VO2 increases from a baseline of 25%. Although there is no clear-cut point, oxygen extraction number between 33 and 40% is considered acceptable and not critical. If the oxygen extraction is high, emphasis should be on delivery components, i.e., Hb, O2 saturation, and cardiac output. If oxygen extraction is standard, there is no physiologic reasoning to increase oxygen delivery by transfusion. Critical oxygen delivery at which anaerobic metabolism sets in and causes lactate production is not well defined.
The ratio of oxygen uptake to delivery is known as the oxygen extraction ratio. The standard O2ER is around 25%. This number is essential and the body tries to compensate by increasing the cardiac output to maintain DO2 when there is a drop in Hb [5]. It is imperative to understand critical oxygen delivery as we now have enough evidence pointing towards euvolemic management rather than increasing the hemoglobin concentration to help with oxygen delivery. We can argue that increasing the inhaled oxygen and keeping a patient on supra-normal FiO2 can increase oxygen delivery, but as noted in the equation above, this intervention does not increase the dissolved oxygen component by much. Hence, cardiac output and hemoglobin concentration plays the primary role in oxygen delivery. Furthermore, we know from animal studies that there is a constant oxygen extraction ratio even under stress, so to secure adequate oxygen delivery or tissue perfusion, the body adjusts by ensuring enough blood flow and hence volume. DO2 is approximately three times and 1.5 times VO2 for the brain and heart muscle, respectively. Brain, heart, and skeletal muscle can maintain adequate blood flow in the setting of varying blood pressure within limits – the phenomenon known as ‘autoregulation’ [6].
Transfusion of blood products is a daily occurrence in many medical ICUs with a predefined goal to improve tissue perfusion. A decline in Hb is likely to cause a decrease in DO2 if cardiac output remains unchanged since DO2 = Cardiac output × CaO2. When delivery is decreased, the body can compensate by increasing VO2 to a certain extent. Since DO2 incorporates Hb, cardiac output, and arterial oxygen saturation, measuring central venous O2 (ScvO2) can help determine oxygen extraction. The constant relationship between VO2-DO2 keeps the body functioning at an optimal level, and the ‘critical level’ at which this dependency is lost leads to tissue dysoxia. This critical level at which tissue dysoxia is usually present when central venous oxygen falls below 40–50% or DO2:VO2 is 2:1 (Figure 1).
Critical O2 delivery. The body responds by extracting more oxygen in cases of decreased DO2. However, once DO2 drops below the critical threshold cellular metabolism becomes anaerobic with the subsequent production of lactate.
If VO2 is low or normal (<33%), the rationale to increase oxygen delivery is disputable. On the other hand, if extraction is more than 40%, this is critical, and an attempt should be to increase delivery. Simple means of measuring oxygen extraction would be to obtain central venous Oxygen concentration. Central venous oxygen concentration can be obtained simply from an indwelling central catheter in internal Jugular or subclavian vein, and this should not be mistaken for a mixed venous oxygen concentration. Mixed venous oxygen concentration (MVO2) from an indwelling pulmonary artery catheter measures the oxygen extraction from both upper and lower extremities. However, both central and mixed venous oxygen concentrations correlate well in assessing sufficient perfusion and are often used interchangeably.
There are multiple studies available that suggest the use of this physiological parameter than an arbitrary lab-based number as a trigger for blood products is a better approach. Kocsi
Hemodynamic monitoring has essentially become the cornerstone in guiding resuscitation for ICU patients. This serves as guide and marker for impending crisis and help determine the therapy that is best fitting. The parameters defined herein are to assist in the bedside assessment and only acts as a supplement to clinical judgment i.e., it should be considered in the context of pathophysiology, and the time point in the disease process [9]. An accurate assessment of volume status and its management remains a challenging issue with clinicians. Stroke volume is the amount of blood ejected (ml) from the left ventricle with each cardiac cycle and is the ultimate response we are trying to improve during resuscitation. Clinicians predict probable response to a fluid challenge by considering various static and dynamic parameters. The age-old tradition of using ‘fluid challenge’ and assessing clinical response has now been contested and multiple studies have shown increased morbidity in surgical and nonsurgical patients when not guided by a parameter. Using parameters such as cardiac index or mixed venous oxygen saturation alone do not help in guiding optimal therapy either. Gattinoni et al. showed that achieving higher levels of oxygen delivery through supranormal cardiac index or normal values of mixed venous oxygen saturation do not change mortality [10].
The static parameters previously used to assess fluid status have proven to be unreliable. Static measurements such as central venous pressure (CVP) or pulmonary artery occlusion pressure (PAOP) have low sensitivity and specificity when used to assess fluid responsiveness. Osman et al. showed that baseline CVP was similar in responders and non-responders by subjecting 96 septic mechanically ventilated patients to fluid boluses. Hence CVP measurements have a low predictive value. Also, many clinicians assume that increases in CVP with a fluid bolus indicate positive fluid responsiveness. The poor reproducibility is explained by the Frank-Starling curve, which varies among patients depending on cardiac function. These parameters are also affected by the change in respiratory system compliance and other cardiac factors. An example of this is the study done by Rivers et al. In the early goal-directed therapy arm of the trial wherein fluids administered targeted a goal CVP measurement [11]. The physiological goal of the fluid administration is to increase preload accompanied by an increased stroke volume and hence cardiac output. A notable increase in CVP with minimal change in the cardiac output or a slight change in CVP but with a notable change in cardiac output can be misleading and used alone can be confusing for clinicians. Targeting CVP, although tempting, should be combined with the after-effects, which include measurement of cardiac output in real-time.
Dynamic measurements are gaining popularity in the current era, and various modalities are available, including passive leg raise testing (PLR), stroke volume variation (SVV), and pulse pressure variation (PPV). PLR although can be used in spontaneously breathing patients, SVV and PPV come with some restrictions and best served in patients on positive pressure ventilation. A systematic review demonstrated that dynamic parameters can be reliably used in predicting fluid responsiveness. Pulse pressure variation during the Valsalva maneuver (∆PPV) of 52% (AUC ± SD: 0.98 ± 0.03) and passive leg raising-induced change in stroke volume (∆SV-PLR) greater than 13% (AUC ± SD: 0.96 ± 0.03) showed the highest accuracy to predict fluid responsiveness in spontaneously breathing patients [12]. Technological advances have allowed us to obtain arterial waveform analysis non-invasively or invasively in the modern-day ICU. By studying the arterial waveform, we can obtain stroke volume variation (SVV) and pulse pressure variation (PPV). A systemic review by Marik et al. demonstrated that fluid responsiveness using area under the curve (AUC) demonstrated the superiority of arterial waveform technology as compared to central venous catheters and transpulmonary dilution. Arterial waveform analysis is instrumental in the intensive care unit (ICU) and key in resuscitation for our ICU patients who already have an arterial line placed.
Dynamic parameters should be used preferentially over static parameters to predict fluid responsiveness in ICU patients. An analysis of 12 studies showed that static parameters such as right atrial pressure, pulmonary artery occlusion pressure, right ventricular end-diastolic volume were not significantly lower in responders vs. non-responders to fluid bolus [13].
A relatively easy bedside test that essentially transfers 300 mL of venous blood to the right heart acts as a fluid bolus. It has significant advantages as it does not require any special equipment, easily performed at bedside and rapidly reversible with no risk of fluid overload. An important point is to directly measure cardiac output before and after the PLR test to assess if there was a notable change to cardiac output. The technique used to measure the cardiac output needs to assess short-term and transient changes to the cardiac output because the effects of PLR usually go away after one minute. This procedure can be performed by sitting the patient at 45 degrees head up in a semi-recumbent position. We lower the patient’s upper body to horizontal and passively raise legs to 45 degrees. This position is sustained for about 30–60 seconds. An assessment of stroke volume (using cardiac output monitor) or pulse pressure change is conducted simultaneously.
A PLR increase of aortic blood flow higher or equal to 10% predicted fluid responsiveness with a sensitivity of 97% and a specificity of 94%. A PLR increase of pulse pressure higher or equal to 12% predicted volume responsiveness with significantly lower sensitivity (60%) and specificity (85%) [14]. A meta-analysis of 21 studies, including more than 900 patients in which cardiac output was measured by echocardiography, pulse contour analysis, bioreactance, esophageal Doppler, transpulmonary thermodilution, or pulmonary artery catheter, showed PLR-induced changes in cardiac output to have a pooled sensitivity of 0.85 and a pooled specificity of 0.91. The area under the curve was 0.95. The best threshold was a PLR-induced increase in cardiac output of greater than 10± 2%. For the PLR induced changes in pulse pressure, the pooled sensitivity was 0.56 (0.49–0.53), the pooled specificity was 0.83 (0.77–0.88), and the pooled area under the ROC curve was 0.77 [15]. Physiologically informed volume resuscitation with the use of the PLR-induced stroke volume change to guide management of shock is safe and demonstrated lower net fluid balance and reductions in the risk of renal and respiratory failure. In this modified intent-to-treat analysis that included 83 intervention and 41 usual care eligible patients, fluid balance at 72 hours or ICU discharge was significantly lower (−1.37 L favoring the intervention arm; 0.65 ± 2.85 L intervention arm vs. 2.02 ± 3.44 L usual care arm; P = 0.021). Fewer patients required renal replacement therapy (5.1% vs. 17.5%; P = 0.04) or mechanical ventilation (17.7% vs. 34.1%; P = 0.04) in the intervention arm compared with usual care [16].
The rationale for using SVV and PPV is that a varying left ventricular stroke volume as a response to cyclic positive pressure indicates that both ventricles are pre-load dependent as described here. SVV is derived from pulse contour analysis and the variation of the amplitude of the pulse oximeter waveform, and PPV is derived from analysis of the arterial waveform.
SVV is defined as a change in volume during the respiratory cycle and calculated as (SV max-SV min)/SV mean. This change represents dynamic variation occurring as a result of changing pleural pressure during a breath. During a positive pressure breath, intermittent increase in the intrathoracic pressure as ventilator cycles causes increased right ventricular afterload and decreased right ventricular preload. Clinically, this manifests as a decrease in left ventricular output and stroke volume after several cardiac cycles. This pressure manages to increase left ventricular preload and reduces left ventricular afterload, resulting in an acute increase in the left ventricular stroke volume harmonizing with the inspiratory phase of positive pressure ventilation. The variability in stroke volume occurring here has been well correlated with fluid responsiveness (Figure 2) [17, 18].
SVV and Frank-Starling curve. SVV is a dynamic variable that predicts volume responsiveness and individualizes the Starling relationship. A: Volume responsive SVV > 13% B: Non-volume responsive SVV < 13%.
SVV has been widely studied in the operating room as it provides ideal conditions. A study by Willars et al., including high risk vascular surgeries compared SVV, PPV, CVP and Delta CVP [19]. The area under the receiver operator curve (AUROC) was 0.75 for SVV, 0.67 for PPV. The best cutoff value for SVV was 13.5%. At this level positive likelihood ratio was 2.7 and negative likelihood ratio of 0.34. They concluded that SVV was the only adequate predictor of fluid responsiveness in this cohort. SVV by itself has some limitations and needs to be used on a case by case basis.
With various parameters now available, we suggest use of a simple physiologic algorithm to help clinicians guide therapy better for these patients. A ‘volume responsive patient’ can be defined using SVV, PPV, and Stroke volume index (SVI). Although there is not a true number that differentiates a true responder to nonresponder, a change of 13% is thought to be appropriate. The reason being SVV is not a binary but more typically linear. Studies have defined the range to be around 10–15%. An algorithm has been proposed in detail going over the pathways that define a comprehensive approach in these patients.
In brief, dynamic changes are best observed with a significant rapid volume challenge. Colloid including blood or larger or lesser amounts of crystalloid may be used depending on the clinical scenario. In patients with SVV less than 13% you can further calculate stroke volume index (SI) as an aid to decide on the most appropriate intervention based on underlying pathophysiology. Because of the influence of heart rate on cardiac output, the preference is to use stroke index data as the measure of cardiac performance (Figure 3) [20].
Physiologic optimization. If SVV < 13% or passive leg raise test is negative, pathway A, B, C further utilizes stroke index (SI) to delineate therapy.
Using this algorithm in ICU patients is quite challenging as it does not consider the rate of oxygen extraction and if volume is likely to alter it. Through advanced hemodynamic monitoring using a combination of SVV and Oxygen delivery we can further understand a patient’s requirements better and an approach can be determined to patient’s care. Most clinical studies were done in patients on positive pressure therapy with normal chest wall compliance, larger tidal volumes and with passive breaths. It should be considered that spontaneous breathing and arrhythmias will lead to misinterpretations of the respiratory variations in the pulse pressure/stroke volume. However, PLR has a higher sensitivity in these two scenarios and still holds value in assessment [14, 15].
The clinician must evaluate for SVV, SI and O2 extraction on a case by case basis. Coupling these parameters assists in determination of adequate Oxygen delivery.
Physiological concepts, such as oxygen delivery and oxygen extraction, when combined with dynamic indices of fluid responsiveness, provide clinicians a more accurate assessment in predicting which cohort of patients accept additional blood or volume without resulting in lung injury. After the TRICC trial, it is a widespread practice to give blood if the Hemoglobin is less than 7 g/dL. However, if physiological parameters mentioned above are not examined, we may give blood or volume to people who do not need it and cannot accept it. By employing a simple physiologic algorithm, we can determine a specific population that will accept volume and prevents unwanted consequences of transfusion-associated lung injury and circulatory overload. This scenario prevents patients from harm and decreases various adverse outcomes, including acute lung injury, increased total body volume, higher morbidity, and mortality.
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His studies in robotics lead him not only to a PhD degree but also inspired him to co-found and build the International Journal of Advanced Robotic Systems - world's first Open Access journal in the field of robotics.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"441",title:"Ph.D.",name:"Jaekyu",middleName:null,surname:"Park",slug:"jaekyu-park",fullName:"Jaekyu Park",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/441/images/1881_n.jpg",biography:null,institutionString:null,institution:{name:"LG Corporation (South Korea)",country:{name:"Korea, South"}}},{id:"465",title:"Dr",name:"Christian",middleName:null,surname:"Martens",slug:"christian-martens",fullName:"Christian Martens",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"479",title:"Dr.",name:"Valentina",middleName:null,surname:"Colla",slug:"valentina-colla",fullName:"Valentina Colla",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/479/images/358_n.jpg",biography:null,institutionString:null,institution:{name:"Sant'Anna School of Advanced Studies",country:{name:"Italy"}}},{id:"494",title:"PhD",name:"Loris",middleName:null,surname:"Nanni",slug:"loris-nanni",fullName:"Loris Nanni",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/494/images/system/494.jpg",biography:"Loris Nanni received his Master Degree cum laude on June-2002 from the University of Bologna, and the April 26th 2006 he received his Ph.D. in Computer Engineering at DEIS, University of Bologna. On September, 29th 2006 he has won a post PhD fellowship from the university of Bologna (from October 2006 to October 2008), at the competitive examination he was ranked first in the industrial engineering area. He extensively served as referee for several international journals. He is author/coauthor of more than 100 research papers. He has been involved in some projects supported by MURST and European Community. 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Delac received his B.Sc.E.E. degree in 2003 and is currentlypursuing a Ph.D. degree at the University of Zagreb, Faculty of Electrical Engineering andComputing. His current research interests are digital image analysis, pattern recognition andbiometrics.",institutionString:null,institution:{name:"University of Zagreb",country:{name:"Croatia"}}},{id:"557",title:"Dr.",name:"Andon",middleName:"Venelinov",surname:"Topalov",slug:"andon-topalov",fullName:"Andon Topalov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/557/images/1927_n.jpg",biography:"Dr. Andon V. Topalov received the MSc degree in Control Engineering from the Faculty of Information Systems, Technologies, and Automation at Moscow State University of Civil Engineering (MGGU) in 1979. He then received his PhD degree in Control Engineering from the Department of Automation and Remote Control at Moscow State Mining University (MGSU), Moscow, in 1984. 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He also obtained an MSc in Molecular and Genetic Medicine, and a Ph.D. in Clinical Immunology and Human Genetics from the University of Sheffield, UK. He also completed a short-term fellowship in Pediatric Clinical Immunology and Bone Marrow Transplantation at Newcastle General Hospital, England. Dr. Rezaei is a Full Professor of Immunology and Vice Dean of International Affairs and Research, at the School of Medicine, Tehran University of Medical Sciences, and the co-founder and head of the Research Center for Immunodeficiencies. He is also the founding president of the Universal Scientific Education and Research Network (USERN). Dr. Rezaei has directed more than 100 research projects and has designed and participated in several international collaborative projects. He is an editor, editorial assistant, or editorial board member of more than forty international journals. 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He worked as a post-doctoral fellow at the Public Health Research Institute (PHRI), Newark, NJ for four years before accepting a three-year faculty position at Brigham Young University-Hawaii. Dr. Engohang-Ndong is a tenured faculty member with the academic rank of Full Professor at Kent State University, Ohio, where he teaches a wide range of biological science courses and pursues his research in medical and environmental microbiology. 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He has an excellent track record in the herpesvirus field, and his group is engaged in clinical research in the field of Epstein-Barr virus diseases. He is the editor of the online Encyclopedia of Environment and he coordinates the Universal Health Coverage education program for the BioHealth Computing Schools of the European Institute of Science.",institutionString:null,institution:{name:"Grenoble Alpes University",country:{name:"France"}}},{id:"131400",title:"Prof.",name:"Alfonso J.",middleName:null,surname:"Rodriguez-Morales",slug:"alfonso-j.-rodriguez-morales",fullName:"Alfonso J. Rodriguez-Morales",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/131400/images/system/131400.png",biography:"Dr. Rodriguez-Morales is an expert in tropical and emerging diseases, particularly zoonotic and vector-borne diseases (especially arboviral diseases). He is the president of the Travel Medicine Committee of the Pan-American Infectious Diseases Association (API), as well as the president of the Colombian Association of Infectious Diseases (ACIN). He is a member of the Committee on Tropical Medicine, Zoonoses, and Travel Medicine of ACIN. He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. His Scopus H index is 47 (Google Scholar H index, 68).",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null},{id:"332819",title:"Dr.",name:"Chukwudi Michael",middleName:"Michael",surname:"Egbuche",slug:"chukwudi-michael-egbuche",fullName:"Chukwudi Michael Egbuche",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/332819/images/14624_n.jpg",biography:"I an Dr. Chukwudi Michael Egbuche. I am a Senior Lecturer in the Department of Parasitology and Entomology, Nnamdi Azikiwe University, Awka.",institutionString:null,institution:{name:"Nnamdi Azikiwe University",country:{name:"Nigeria"}}},{id:"284232",title:"Mr.",name:"Nikunj",middleName:"U",surname:"Tandel",slug:"nikunj-tandel",fullName:"Nikunj Tandel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284232/images/8275_n.jpg",biography:'Mr. Nikunj Tandel has completed his Master\'s degree in Biotechnology from VIT University, India in the year of 2012. He is having 8 years of research experience especially in the field of malaria epidemiology, immunology, and nanoparticle-based drug delivery system against the infectious diseases, autoimmune disorders and cancer. He has worked for the NIH funded-International Center of Excellence in Malaria Research project "Center for the study of complex malaria in India (CSCMi)" in collaboration with New York University. The preliminary objectives of the study are to understand and develop the evidence-based tools and interventions for the control and prevention of malaria in different sites of the INDIA. Alongside, with the help of next-generation genomics study, the team has studied the antimalarial drug resistance in India. Further, he has extended his research in the development of Humanized mice for the study of liver-stage malaria and identification of molecular marker(s) for the Artemisinin resistance. At present, his research focuses on understanding the role of B cells in the activation of CD8+ T cells in malaria. 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She is currently an Adjunct Professor at Feevale University in Medicine and Biomedicine courses and a permanent professor of the Academic Master\\'s Degree in Virology. She has experience in the field of Microbiology, with an emphasis on Bacteriology, working mainly on the following topics: bacteriophages, bacterial resistance, clinical microbiology and food microbiology.",institutionString:null,institution:{name:"Universidade Feevale",country:{name:"Brazil"}}},{id:"229220",title:"Dr.",name:"Amjad",middleName:"Islam",surname:"Aqib",slug:"amjad-aqib",fullName:"Amjad Aqib",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229220/images/system/229220.png",biography:"Dr. Amjad Islam Aqib obtained a DVM and MSc (Hons) from University of Agriculture Faisalabad (UAF), Pakistan, and a PhD from the University of Veterinary and Animal Sciences Lahore, Pakistan. 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Professor Derbel is presently working at the Clinique les Oliviers, Sousse, Tunisia. His hospital activities are mostly concerned with laparoscopic, colorectal, pancreatic, hepatobiliary, and gastric surgery. He is also very interested in hernia surgery and performs ventral hernia repairs and inguinal hernia repairs. He has been a member of the GREPA and Tunisian Hernia Society (THS). During his residency, he managed patients suffering from diabetic foot, and he was very interested in this pathology. For this reason, he decided to coordinate a book project dealing with the diabetic foot. Professor Derbel has published many articles in journals and collaborates intensively with IntechOpen Access Publisher as an editor.",institutionString:"Clinique les Oliviers",institution:null},{id:"300144",title:"Dr.",name:"Meriem",middleName:null,surname:"Braiki",slug:"meriem-braiki",fullName:"Meriem Braiki",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/300144/images/system/300144.jpg",biography:"Dr. Meriem Braiki is a specialist in pediatric surgeon from Tunisia. She was born in 1985. She received her medical degree from the University of Medicine at Sousse, Tunisia. She achieved her surgical residency training periods in Pediatric Surgery departments at University Hospitals in Monastir, Tunis and France.\r\nShe is currently working at the Pediatric surgery department, Sidi Bouzid Hospital, Tunisia. Her hospital activities are mostly concerned with laparoscopic, parietal, urological and digestive surgery. She has published several articles in diffrent journals.",institutionString:"Sidi Bouzid Regional Hospital",institution:null},{id:"229481",title:"Dr.",name:"Erika M.",middleName:"Martins",surname:"de Carvalho",slug:"erika-m.-de-carvalho",fullName:"Erika M. de Carvalho",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229481/images/6397_n.jpg",biography:null,institutionString:null,institution:{name:"Oswaldo Cruz Foundation",country:{name:"Brazil"}}},{id:"186537",title:"Prof.",name:"Tonay",middleName:null,surname:"Inceboz",slug:"tonay-inceboz",fullName:"Tonay Inceboz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/186537/images/system/186537.jfif",biography:"I was graduated from Ege University of Medical Faculty (Turkey) in 1988 and completed his Med. PhD degree in Medical Parasitology at the same university. I became an Associate Professor in 2008 and Professor in 2014. I am currently working as a Professor at the Department of Medical Parasitology at Dokuz Eylul University, Izmir, Turkey.\n\nI have given many lectures, presentations in different academic meetings. I have more than 60 articles in peer-reviewed journals, 18 book chapters, 1 book editorship.\n\nMy research interests are Echinococcus granulosus, Echinococcus multilocularis (diagnosis, life cycle, in vitro and in vivo cultivation), and Trichomonas vaginalis (diagnosis, PCR, and in vitro cultivation).",institutionString:"Dokuz Eylül University",institution:{name:"Dokuz Eylül University",country:{name:"Turkey"}}},{id:"71812",title:"Prof.",name:"Hanem Fathy",middleName:"Fathy",surname:"Khater",slug:"hanem-fathy-khater",fullName:"Hanem Fathy Khater",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/71812/images/1167_n.jpg",biography:"Prof. Khater is a Professor of Parasitology at Benha University, Egypt. She studied for her doctoral degree, at the Department of Entomology, College of Agriculture, Food and Natural Resources, University of Missouri, Columbia, USA. She has completed her Ph.D. degrees in Parasitology in Egypt, from where she got the award for “the best scientific Ph.D. dissertation”. She worked at the School of Biological Sciences, Bristol, England, the UK in controlling insects of medical and veterinary importance as a grant from Newton Mosharafa, the British Council. Her research is focused on searching of pesticides against mosquitoes, house flies, lice, green bottle fly, camel nasal botfly, soft and hard ticks, mites, and the diamondback moth as well as control of several parasites using safe and natural materials to avoid drug resistances and environmental contamination.",institutionString:null,institution:{name:"Banha University",country:{name:"Egypt"}}},{id:"99780",title:"Prof.",name:"Omolade",middleName:"Olayinka",surname:"Okwa",slug:"omolade-okwa",fullName:"Omolade Okwa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/99780/images/system/99780.jpg",biography:"Omolade Olayinka Okwa is presently a Professor of Parasitology at Lagos State University, Nigeria. She has a PhD in Parasitology (1997), an MSc in Cellular Parasitology (1992), and a BSc (Hons) Zoology (1990) all from the University of Ibadan, Nigeria. She teaches parasitology at the undergraduate and postgraduate levels. She was a recipient of a Commonwealth fellowship supported by British Council tenable at the Centre for Entomology and Parasitology (CAEP), Keele University, United Kingdom between 2004 and 2005. She was awarded an Honorary Visiting Research Fellow at the same university from 2005 to 2007. \nShe has been an external examiner to the Department of Veterinary Microbiology and Parasitology, University of Ibadan, MSc programme between 2010 and 2012. She is a member of the Nigerian Society of Experimental Biology (NISEB), Parasitology and Public Health Society of Nigeria (PPSN), Science Association of Nigeria (SAN), Zoological Society of Nigeria (ZSN), and is Vice Chairperson of the Organisation of Women in Science (OWSG), LASU chapter. She served as Head of Department of Zoology and Environmental Biology, Lagos State University from 2007 to 2010 and 2014 to 2016. She is a reviewer for several local and international journals such as Unilag Journal of Science, Libyan Journal of Medicine, Journal of Medicine and Medical Sciences, and Annual Research and Review in Science. \nShe has authored 45 scientific research publications in local and international journals, 8 scientific reviews, 4 books, and 3 book chapters, which includes the books “Malaria Parasites” and “Malaria” which are IntechOpen access publications.",institutionString:"Lagos State University",institution:{name:"Lagos State University",country:{name:"Nigeria"}}},{id:"273100",title:"Dr.",name:"Vijay",middleName:null,surname:"Gayam",slug:"vijay-gayam",fullName:"Vijay Gayam",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/273100/images/system/273100.jpeg",biography:"Dr. Vijay Bhaskar Reddy Gayam is currently practicing as an internist at Interfaith Medical Center in Brooklyn, New York, USA. He is also a Clinical Assistant Professor at the SUNY Downstate University Hospital and Adjunct Professor of Medicine at the American University of Antigua. He is a holder of an M.B.B.S. degree bestowed to him by Osmania Medical College and received his M.D. at Interfaith Medical Center. His career goals thus far have heavily focused on direct patient care, medical education, and clinical research. He currently serves in two leadership capacities; Assistant Program Director of Medicine at Interfaith Medical Center and as a Councilor for the American\r\nFederation for Medical Research. As a true academician and researcher, he has more than 50 papers indexed in international peer-reviewed journals. He has also presented numerous papers in multiple national and international scientific conferences. His areas of research interest include general internal medicine, gastroenterology and hepatology. He serves as an editor, editorial board member and reviewer for multiple international journals. His research on Hepatitis C has been very successful and has led to multiple research awards, including the 'Equity in Prevention and Treatment Award” from the New York Department of Health Viral Hepatitis Symposium (2018) and the 'Presidential Poster Award” awarded to him by the American College of Gastroenterology (2018). He was also awarded 'Outstanding Clinician in General Medicine” by Venus International Foundation for his extensive research expertise and services, perform over and above the standard expected in the advancement of healthcare, patient safety and quality of care.",institutionString:"Interfaith Medical Center",institution:{name:"Interfaith Medical Center",country:{name:"United States of America"}}},{id:"93517",title:"Dr.",name:"Clement",middleName:"Adebajo",surname:"Meseko",slug:"clement-meseko",fullName:"Clement Meseko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/93517/images/system/93517.jpg",biography:"Dr. Clement Meseko obtained DVM and PhD degree in Veterinary Medicine and Virology respectively. He has worked for over 20 years in both private and public sectors including the academia, contributing to knowledge and control of infectious disease. Through the application of epidemiological skill, classical and molecular virological skills, he investigates viruses of economic and public health importance for the mitigation of the negative impact on people, animal and the environment in the context of Onehealth. \r\nDr. Meseko’s field experience on animal and zoonotic diseases and pathogen dynamics at the human-animal interface over the years shaped his carrier in research and scientific inquiries. He has been part of the investigation of Highly Pathogenic Avian Influenza incursions in sub Saharan Africa and monitors swine Influenza (Pandemic influenza Virus) agro-ecology and potential for interspecies transmission. He has authored and reviewed a number of journal articles and book chapters.",institutionString:"National Veterinary Research Institute",institution:{name:"National Veterinary Research Institute",country:{name:"Nigeria"}}},{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",biography:"Professor Dr. Shailendra K. Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. Dr. Saxena is a fellow of various international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. He is also an international opinion leader/expert in vaccination for Japanese encephalitis by IPIC (UK).",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",country:{name:"India"}}},{id:"94928",title:"Dr.",name:"Takuo",middleName:null,surname:"Mizukami",slug:"takuo-mizukami",fullName:"Takuo Mizukami",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94928/images/6402_n.jpg",biography:null,institutionString:null,institution:{name:"National Institute of Infectious Diseases",country:{name:"Japan"}}},{id:"233433",title:"Dr.",name:"Yulia",middleName:null,surname:"Desheva",slug:"yulia-desheva",fullName:"Yulia Desheva",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/233433/images/system/233433.png",biography:"Dr. Yulia Desheva is a leading researcher at the Institute of Experimental Medicine, St. Petersburg, Russia. She is a professor in the Stomatology Faculty, St. Petersburg State University. She has expertise in the development and evaluation of a wide range of live mucosal vaccines against influenza and bacterial complications. Her research interests include immunity against influenza and COVID-19 and the development of immunization schemes for high-risk individuals.",institutionString:'Federal State Budgetary Scientific Institution "Institute of Experimental Medicine"',institution:null},{id:"238958",title:"Mr.",name:"Atamjit",middleName:null,surname:"Singh",slug:"atamjit-singh",fullName:"Atamjit Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/238958/images/6575_n.jpg",biography:null,institutionString:null,institution:null},{id:"333753",title:"Dr.",name:"Rais",middleName:null,surname:"Ahmed",slug:"rais-ahmed",fullName:"Rais Ahmed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333753/images/20168_n.jpg",biography:null,institutionString:null,institution:null},{id:"252058",title:"M.Sc.",name:"Juan",middleName:null,surname:"Sulca",slug:"juan-sulca",fullName:"Juan Sulca",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252058/images/12834_n.jpg",biography:null,institutionString:null,institution:null},{id:"191392",title:"Dr.",name:"Marimuthu",middleName:null,surname:"Govindarajan",slug:"marimuthu-govindarajan",fullName:"Marimuthu Govindarajan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/191392/images/5828_n.jpg",biography:"Dr. M. Govindarajan completed his BSc degree in Zoology at Government Arts College (Autonomous), Kumbakonam, and MSc, MPhil, and PhD degrees at Annamalai University, Annamalai Nagar, Tamil Nadu, India. He is serving as an assistant professor at the Department of Zoology, Annamalai University. His research interests include isolation, identification, and characterization of biologically active molecules from plants and microbes. He has identified more than 20 pure compounds with high mosquitocidal activity and also conducted high-quality research on photochemistry and nanosynthesis. He has published more than 150 studies in journals with impact factor and 2 books in Lambert Academic Publishing, Germany. He serves as an editorial board member in various national and international scientific journals.",institutionString:null,institution:null},{id:"274660",title:"Dr.",name:"Damodar",middleName:null,surname:"Paudel",slug:"damodar-paudel",fullName:"Damodar Paudel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/274660/images/8176_n.jpg",biography:"I am DrDamodar Paudel,currently working as consultant Physician in Nepal police Hospital.",institutionString:null,institution:null},{id:"241562",title:"Dr.",name:"Melvin",middleName:null,surname:"Sanicas",slug:"melvin-sanicas",fullName:"Melvin Sanicas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241562/images/6699_n.jpg",biography:null,institutionString:null,institution:null},{id:"337446",title:"Dr.",name:"Maria",middleName:null,surname:"Zavala-Colon",slug:"maria-zavala-colon",fullName:"Maria Zavala-Colon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Puerto Rico, Medical Sciences Campus",country:{name:"United States of America"}}},{id:"338856",title:"Mrs.",name:"Nur Alvira",middleName:null,surname:"Pascawati",slug:"nur-alvira-pascawati",fullName:"Nur Alvira Pascawati",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universitas Respati Yogyakarta",country:{name:"Indonesia"}}},{id:"441116",title:"Dr.",name:"Jovanka M.",middleName:null,surname:"Voyich",slug:"jovanka-m.-voyich",fullName:"Jovanka M. Voyich",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Montana State University",country:{name:"United States of America"}}},{id:"330412",title:"Dr.",name:"Muhammad",middleName:null,surname:"Farhab",slug:"muhammad-farhab",fullName:"Muhammad Farhab",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Agriculture Faisalabad",country:{name:"Pakistan"}}},{id:"349495",title:"Dr.",name:"Muhammad",middleName:null,surname:"Ijaz",slug:"muhammad-ijaz",fullName:"Muhammad Ijaz",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Veterinary and Animal Sciences",country:{name:"Pakistan"}}}]}},subseries:{item:{id:"6",type:"subseries",title:"Viral Infectious Diseases",keywords:"Novel Viruses, Virus Transmission, Virus Evolution, Molecular Virology, Control and Prevention, Virus-host Interaction",scope:"The Viral Infectious Diseases Book Series aims to provide a comprehensive overview of recent research trends and discoveries in various viral infectious diseases emerging around the globe. The emergence of any viral disease is hard to anticipate, which often contributes to death. A viral disease can be defined as an infectious disease that has recently appeared within a population or exists in nature with the rapid expansion of incident or geographic range. This series will focus on various crucial factors related to emerging viral infectious diseases, including epidemiology, pathogenesis, host immune response, clinical manifestations, diagnosis, treatment, and clinical recommendations for managing viral infectious diseases, highlighting the recent issues with future directions for effective therapeutic strategies.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/6.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11402,editor:{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. 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Dr. Saxena is a fellow of various international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. 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Biochemistry examines macromolecules - proteins, nucleic acids, carbohydrates, and lipids – and their building blocks, structures, functions, and interactions. Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. 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Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. 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In recent years, the application of chemistry to biological molecules has gained significant interest in medicinal and pharmacological studies. This topic will be devoted to understanding the interplay between biomolecules and chemical compounds, their structure and function, and their potential applications in related fields. Being a part of the biochemistry discipline, the ideas and concepts that have emerged from Chemical Biology have affected other related areas. 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Behind these definitions are hidden all the aspects of normal and pathological functioning of all processes that the topic ‘Metabolism’ will cover within the Biochemistry Series. 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Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. 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