\r\n\tThis book aims to explore the issues around the rheology of polymers, with an emphasis on biopolymers as well as the modification of polymers using reactive extrusion.
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1. Introduction
The medical effects of dysphagia, including dehydration, malnutrition, and aspiration, that lead to pneumonia are well documented throughout the literature, as are the negative consequences of dysphagia on an individual’s functioning and quality of life. What is less known, however, is how the family members of people with dysphagia are impacted by this condition. Understanding the issues faced by individuals who support and care for family members with dysphagia, and exploring how health professionals can best support the needs of the entire family is an important and emerging area of both research and clinical practice.
2. The biopsychosocial effects of dysphagia
Dysphagia is traditionally defined as a difficulty or abnormality in swallowing. In adulthood, it is predominantly an acquired condition and may result from a wide variety of etiologies. It can also result from changes associated with the effects of normal aging [1]. Over the past four decades, the bulk of research conducted in the field of dysphagia and its management has focused on understanding this condition at an impairment level. Through this historical body of work, swallowing is now understood to be a complex physiological process that involves precision timing and coordination of multiple structures within the neuromuscular system. Oropharyngeal dysphagia can be associated with a range of physiological impairments, which may lead to difficulty in oral preparation of the bolus, moving the bolus posteriorly toward the pharynx, triggering and coordinating the pharyngeal swallow, clearing the bolus into the upper esophagus, and protecting the airway from food and fluid entry [2]. Depending on the etiology of the condition causing dysphagia, individuals may also be affected by associated impairments such as xerostomia (dry mouth), taste changes, or excessive secretions that may further impact capacity, motivation, and desire to eat. The associated medical effects resulting from difficulty in swallowing may include dehydration, malnutrition [3], and respiratory dysfunction (including pneumonia) [4], and ultimately can lead to death in severe cases [5].
The traditional management approaches that have evolved in parallel with our understanding of the process of normal swallowing have also been predominantly based on impairment. Interventions including postural strategies, swallowing techniques, and modification of food and fluid textures are used as first-line treatment options to compensate for specific physiological impairments and to improve the efficiency and safety of oropharyngeal swallowing function. Active rehabilitation programs, which are typically implemented in parallel to compensatory measures, are developed following a combination of clinical and objective assessments (videofluoroscopy or fiber-optic endoscopic evaluation of swallowing) and involve behavioral and medical interventions designed to improve swallowing physiology for long-term gain.
While management services for adult-acquired dysphagia remain predominantly focused on remediating physiological impairments, in particular, the need to consider the wider psychosocial impacts of dysphagia has been highlighted in the past decade. It is now recognized that health professionals must consider dysphagia and its effects more broadly, and that dysphagia is, in fact, a multifaceted condition. In addition to its impact on the medical condition of the individual, dysphagia has also been demonstrated to effect functioning in daily life and overall quality of life [6]. Eating and drinking is a source of human pleasure. Dysphagia can make this process and the activities surrounding it laborious, uncomfortable, and difficult [7]. Irrespective of the cause, dysphagia has been found to have a significant negative impact on the quality of life both immediately and months or years following its onset [5, 6, 8]. In the geriatric population, reduced quality of life has been associated with self-perceived swallowing difficulties, a condition that older people did not necessarily associate with normal aging [9].
Recent studies have also demonstrated the impact of dysphagia on psychosocial health. In a population-based study, dysphagia was reported by 16% of those surveyed, with intermittent dysphagia associated with anxiety and progressive dysphagia associated with depression [10]. Anxiety and depression are also significantly worse in head and neck cancer survivors with dysphagia than those without dysphagia, irrespective of treatment type [8, 11]. For people with dysphagia, difficulty in swallowing has been found to affect socialization, eating out, family rituals, cooking, and shopping [12-14]. As such, the concept of dysphagia needs to be reconsidered. Dysphagia is more than simply a physical difficulty. Rather it represents a complex and multilayered condition that may impact on a person’s physical, emotional, and social life and carries significant burden surrounding functioning in everyday activities.
In order to embrace a wider view of dysphagia, a new conceptual framework is required. The International Classification of Functioning, Disability and Health (ICF) [15] (Figure 1) has been both proposed [16] and used [17-21] as a consistent and universal taxonomy to report research outcomes regarding dysphagia. The ICF is a conceptual framework that provides a biopsychosocial perspective of functioning, and uses an internationally recognized language [15]. It has the potential to describe the far-reaching complexities of dysphagia through the consideration of functioning from the perspective of the body, the individual, and society in two parts: (1) functioning and disability and (2) contextual factors [15]. Functioning and disability comprises (a) the body functions and body structures and (b) activities and participation. The contextual factors are comprised of (a) environmental factors and (b) personal factors (WHO, 2001) (Figure 1).
Each of the components of the ICF consists of various domains and categories that are referred to as the units of classification. Therefore, the functioning of an individual with a health condition can be documented using the appropriate category code and then adding qualifiers, which are numeric codes that specify the magnitude of the individual’s functioning or disability within that category [15]. An alphanumeric coding system is used for coding health conditions in the ICF. The letters b, s, d, and e represent body functions, body structures, activities and participation, and environmental factors respectively. A numeric code then follows these letters, which denotes the domain (or chapter number), followed by additional sublevels of coding, and then the qualifiers (WHO, 2001). For example, changes to taste would be linked to the code b250 - taste function where b represents the body functions domain and the numbers (i.e., 250) represent the various levels of classification.
Figure 1.
International Classification of Functioning, Disability and Health (ICF) [15]
Recently, a study examining the consumer’s perspective of living with dysphagia following management for head and neck cancer utilized the ICF to classify patients’ physical, emotional, and psychosocial concerns relating to their dysphagia [20]. The results demonstrated that dysphagia impacted on body functions, activities and participation, and environmental factors almost equally, with changes to body structures rarely mentioned by people with dysphagia. Therefore when dysphagia is examined more broadly, using a framework such as the ICF, it clearly has far-reaching life effects beyond the physiological changes to the swallow and the medical implications of dysphagia.
3. The effects of dysphagia on the family
Mealtimes, eating, and drinking are profoundly social activities that sustain not only our physiological needs but also our social and emotional life [22]. The meanings we attach to food, and the processes of eating and swallowing are deeply connected to our most valued activities and experiences, and are integral to how we see ourselves as individuals and in relation to others [23]. As such the negative effects of dysphagia are recognized to influence more than just the life of the person with the condition.
In a recent study that mapped the experiences of living with dysphagia following nonsurgical head and neck cancer management to the ICF, a number of environmental factors were identified to influence the functioning (and disability) of the individuals with dysphagia [20]. In particular, family members were identified as important sources of support for people with dysphagia throughout the trajectory of care, particularly in regards to meal preparation and the encouragement to keep eating [20]. In addition to playing an important support role, there is emerging evidence to indicate that families also experience negative effects as a result of living with and supporting individuals with dysphagia [24-26]. For the purposes of this chapter, family is defined as any individual who plays a significant role in the life of the person with dysphagia. This definition encompasses a broad concept of family, and is consistent with other literature, whereby family is described as being two or more people who are related in any way, including through a continuing biological, legal, or emotional relationship [27].
Recent research has demonstrated the pervasive effects of dysphagia on family members following a number of different etiologies including head and neck cancer treatment [24, 26, 28, 29], stroke [25], traumatic brain injury [25], and motor neuron disease [30]. This body of evidence has revealed that families are important members of the support team for people with dysphagia as they provide valuable practical and emotional support. The high levels of burden experienced by family members in relation to food and meal preparation may hinder their ability to function effectively as a support system for the individual with dysphagia [24, 26, 31]. It can also affect their physical and psychological health, and quality of life [24, 25, 32].
Verdonck de Leeuw et al. [32] found that the presence of a gastrostomy tube, a surrogate indicator of dysphagia, in people with head and neck cancer was the only significant predictor of distress in family carers. Supporting this, the family members of people with head and neck cancer and dysphagia have been shown to experience a reduced quality of life both before cancer treatment and in the early acute phase, with significant improvements shown between 3 and 12 months post-treatment [24]. Evidence supports that the family member’s quality of life was found to significantly correlate with the functioning of their family member with dysphagia [24]. Therefore, the presence of dysphagia has the potential to have significant effects, not only on the life of the person with dysphagia but also on their family. Despite differing etiologies, family members of people with dysphagia consistently report negative effects on their everyday lives as a result of the dysphagia particularly in relation to: managing modified diets/fluids, and providing appropriate meals; negative influences of dysphagia on family dynamics and social activities; and the emotional impacts of dysphagia [24-26, 28-30].
3.1. Managing modified diets and fluids and providing appropriate meals
A number of studies have noted that family members of people with dysphagia report experiencing distress associated with food preparation and mealtime activities [24-26, 31]. Consistently across multiple studies, family members reported changes to their meal preparation, noting a need for more conscious and intentional thought and planning, and the need to cook two separate meals [24-26]. Preparing food and meals is one of the most significant ways of providing care, and demonstrating love and concern for others [22, 24, 33]. Though often discounted as trivial, there are a number of important skills involved in the work of “feeding the family” [22]. These skills include: planning meals, learning the food preferences of others, learning about food and preparation techniques, provisioning and shopping for food, preparing meals, serving meals, feeding, and cleaning up from meals.
Meals have been described as fundamental to our daily thinking and acting and are core component to how we organize our days [34]. It is has been estimated that the average person makes over 260 decisions a day regarding eating and that more than 200 of these choices are made subconsciously [35]. When it comes to preparing meals for an individual with dysphagia, decisions regarding eating and drinking are likely to increase and will likely no longer be subconscious. Putting a meal together requires more than cooking as it takes “thoughtful foresight, simultaneous attention to several different aspects of a project, and a continuing openness to ongoing events and interactions” (p. 55) [22]. When a family member has dysphagia, putting a meal together becomes a more intense and time-consuming process [26].
3.2. Influence of dysphagia on family dynamics and social activities
Dysphagia has a recognized influence on family dynamics [24-26, 30, 31]. Many families report the need to accommodate the needs of their family member with dysphagia and consistently find a disruption to family mealtimes [26]. For a number of families, their meals are now dictated by what their family member with dysphagia can eat and some families also eat textured modified diets [26]. In addition, several families have commented that they no longer ate meals together as they did not want to eat in front of their family member with dysphagia [26, 30]. Those that did reported changes to the meaning and experiences of family meals [24-26]. In some studies family members reported leaving the dinner table because they could not cope with their family member’s dysphagia [25, 26]. Family mealtimes are often acknowledged as an important get-together time to enrich family life and “eating together means staying together” (p. 11) [34]. When one member of the family can no longer fully engage in the mealtime experience because of dysphagia, the effects are felt by the entire family unit as there is a loss in the social bonds of food and meals [24-26, 30, 31].
The effects of dysphagia, on family members at mealtimes, are not limited to the home. Numerous studies have documented the negative effects of dysphagia on family member’s social lives including eating out at restaurants and attending significant events such as weddings and holidays leading to further feelings of frustration and isolation [24-26]. Some family members reported looking for opportunities to eat foods that their family member could no longer eat when their family member with dysphagia was not present [26]. Despite the disruptions to family meals and social engagements, the family members in one study reported that they believed the dysphagia did not have a significant impact on their relationship, but had in fact brought them closer together, indicating that family members learn to adapt and adjust to the dysphagia [26].
3.3. Emotional impacts of dysphagia
Numerous emotional impacts of dysphagia on family members have been discussed in the current literature. These emotional impacts have been expressed around a variety of areas. Johansson and Johansson [25] noted that family members of people with dysphagia following stroke or traumatic brain injury expressed concern about their family member’s health and well-being, particularly regarding nutrition, weight maintenance, and the need to pay special attention to texture-modified diets. These findings are similar to those found in family members of people with dysphagia following head and neck cancer. Both Patterson et al. [24] and Nund et al. [26] discussed feelings of fear, guilt, frustration, anger, stress, and helplessness over the enforced changes to meal preparation [24,26]. In addition, family members expressed feelings of insecurity, uncertainty, loneliness, and frustration [24-26] when leaving the care of the hospital services. Family members in these studies reported feeling ill-prepared and anxious regarding the increased responsibilities for their family member’s food and eating [25-27]. These findings across studies highlight the need for specific interventions for family members to build capacity and provide support in the multiple roles they undertake in caring for their family member with dysphagia [26].
4. Third-party disability in dysphagia
The impact of dysphagia on an individual’s family is increasingly being acknowledged as an important consequence of dysphagia [24-26]. The effects of a health condition, such as dysphagia, on the functioning (and disability) of family has been termed “third-party disability” and identified as an area for future work by the WHO [15]. The concept of third-party disability is raised in the situation where the family member may not have a health condition; however, they may experience activity limitations and participation restrictions as a result of their family member’s dysphagia.
Although the concept of third-party disability is still under some conceptual debate, to date the ICF has been used successfully to describe the third-party disability of spouses of older people with hearing impairment [36]; close family members of people with aphasia [37]; and more recently, family members of people with dysphagia following head and neck cancer [38]. A model extending the ICF to explain third-party disability has been proposed [36] and an adapted version of this model, specifically relating to dysphagia, is shown in Figure 2. This adapted model demonstrates how the functioning and disability of an individual with dysphagia acts as an environmental factor for the family member, influencing their functioning (and disability).
Figure 2.
Application of the ICF to family members of people with dysphagia (adapted from Scarinci et al. [36])
In a recent study that mapped family members ‘ experience of dysphagia following head and neck cancer to the ICF, Nund et al. [38] found that the majority of their concerns were linked to the activities and participation component of the ICF (e.g., difficulties or changes to meal preparation were linked to the activities and participation component). It should be noted, however, that these difficulties were generally determined to be performance problems rather than capacity limitations [38]. The difficulties experienced by family members regarding meal preparation were not related to impairments in their body functions, or even in their capacity to prepare a meal. Rather, family members reported experiencing difficulties preparing meals because their family member with dysphagia had specific requirements regarding food and fluids [38].
This finding is consistent with the definition of third-party disability whereby although the family member does not have a health condition, they experience activity limitations and participation restrictions as a result of their partner’s health condition (i.e., as a result of their partner’s dysphagia) [14]. In this mapping process, it was observed that the most relevant domains of the activities and participation component of the ICF were those of interpersonal interactions and relationships, domestic life, general tasks and demands, learning and applying knowledge, self-care, major life areas, and community, social and civic life [38]. The number of relevant activity and participation domains highlights the pervasive effects of dysphagia on the life of the carer and demonstrates that food and meals underpin a number of life areas for family members of head and neck cancer survivors with dysphagia. This study confirmed that ICF terminology can be used successfully to describe the multifaceted and complex effects of dysphagia on family members of people treated nonsurigcally for head and neck cancer.
5. Strategies used by family members to cope with dysphagia
In reponse to the pervasive effects of dysphagia, studies reported to date have identified a number of strategies and processes family members adopt to adjust and cope with their family member’s dysphagia and the associated impacts on their life [24-26]. A predominant theme across studies is the acceptance of a new normal. That is accepting that meal preparation, mealtimes, and social occassions may never be the same. In order to reach this point, family members across studies noted the need to negotiate changing roles in regards to their family members dysphagia and the need to take on more roles within the household [24-26].
Other strategies reported by family members include maintaining a positive attitude; looking for opportunities to eat foods that their partner could not eat when they were not present; and using trial and error strategies to learn what foods their family member could and could not eat. Each of these strategies and adjustment processes were often made without the support of health professionals and family members across studies have consistently reported the need for further education, training, and support from health professionals to help them adapt and adjust to their family member’s dysphagia regardless of etiology or severity of dysphagia [25, 26, 29].
6. Role of family-centered care in dysphagia management
Given the emerging evidence supporting the important role of family members in the provision of informal care for people with dysphagia, and the potential for third-party disability in family members of people with dysphagia, active involvement of family members in all aspects of dysphagia assessment and intervention is clearly indicated. This could be achieved in dysphagia management by shifting from a patient-focused, impairment-based model of intervention, to providing a more holistic, family-centered approach. The Institute for Patient- and Family-Centered Care [39] define family-centered care (FCC) as “... an approach to the planning, delivery, and evaluation of healthcare that is governed by mutually beneficial partnerships between healthcare providers, patients and families.” Although traditionally used in pediatrics, FCC can be applied to people of all ages, and used in any health care setting [39, 40].
The term “family-centered care” is sometimes used synonymously with patient-centered care and client-centered care. However, an important distinction between FCC and the other forms of centeredness is that FCC seeks to explicitly assist families in ways that are important to family members [41, 42]. As such, FCC ensures that care is planned around the whole family; and importantly, the entire family is recognized as receivers of care, not just the individual with dysphagia [43, 44]. In the context of third-party disability, FCC is the most relevant type of centeredness in health care because it emphasizes the importance of health care that is mutually beneficial to all [45].
The principles of FCC originated in the field of psychology, and specifically, family-systems theory. According to family-systems theory, the behavior of any individual should be viewed in the context of their family’s social system [46]. This consideration is supported by empirical evidence showing that family relationships affect biological systems, psychological well-being, and health behavior [47]. Therefore, consideration of the contribution of family relationships to health outcomes is an important consideration for any health service. Family-systems theory also supports the notion that family members play an important role in promoting ongoing change and development in an individual’s functioning, and these changes have the potential to affect the entire family unit.
Given FCC has its roots in theories from psychology, there is a body of evidence in the field of psychology supporting the efficacy of involving family members in interventions. The range of psychological disorders for which involvement of family members has been investigated has been diverse, but includes such conditions as obsessive compulsive disorder and problem-gambling [48-57]. This body of research has shown that interventions that include family members are more effective than individual treatment [52, 54]. Research has also demonstrated that the inclusion of family members in intervention increases opportunities for the family to improve their communication [53, 57]. Involvement of family members also allows professionals to obtain a more holistic view of the true impact of the problem as well as the role of family dynamics [56].
Research in pediatric health care has long demonstrated the benefits of FCC for children with a variety of health conditions. A recent systematic review highlighted the benefits for both patients and family members in terms of improvements in the health condition, improved efficiencies and access to health care services, and improved communication between health care professionals and families [58]. In terms of family functioning, a meta-analysis by Dunst et al. [59] also showed improved family behavior and functioning as a result of FCC. More recently, the application of FCC to adult health care services has been discussed in the literature [40], with a number of documented benefits. Studies have shown that active engagement of family members in medical consultations for patients with chronic conditions results in greater patient engagement in decision making [60], improved recall of information [61], improved satisfaction with care and health-related quality of life [62, 63], increased compliance with medical treatments [64], decreased depression rates, and overall better family dynamics for patients and family members [65, 66]. These benefits have been shown to be especially strong for families of patients with physical health conditions due to the physical assistance provided by these family members on a daily basis [67-69]. In the case of dysphagia, it is expected that due to the chronic nature of this condition and the ongoing supports required by family members in mealtime preparation and assistance, the application of FCC for this population would yield similar benefits.
The Institute for Patient- and Family-Centered Care [39] describes four key components for applying FCC, which could be implemented in dysphagia management: (1) respect and dignity for patients and family members, such that health care professionals listen to and honor the perspectives and choices of patients and family members; (2) the provision of complete and unbiased information to patients and family members such that they can participate effectively in the decision-making process; (3) participation of patients and family members in all aspects of care and decision making; and (4) collaboration with patients and family members in all levels of health care, including policy and program development, implementation and evaluation, facility design, professional education, and in the delivery of care.
In listening and honoring the perspective and choices of people with dysphagia and their family members, clinicians should follow the recommendations outlined by Laidsaar-Powell et al. [70] in order to optimize family member involvement. These include: encouraging, welcoming and involving family members in all aspects of the consultation; and determining the reason for the presence of family members from the perspective of both the patient and family member. Although family members of people with dysphagia may attend consultations with the patient, their role may traditionally be viewed by the health professional as that of “support person” for the individual with dysphagia. However, a recent systematic review of family member involvement in physician consultations highlighted that family members may play a number of roles in supporting patients, ranging from being a memory aide and transcriber to providing emotional support and serving as an advocate and interpreter [70].
A narrow perception of these roles by health professionals may serve to prevent full and active participation in the management plan, with a recent study indicating that health professionals may miss valuable opportunities for engaging family members in designing chronic care management plans, and failing to facilitate participation of family members in consultations [71]. Thus, in order to facilitate FCC in dysphagia management, clinicians should not only be mindful of highlighting helpful behaviors from family members; but also clarifying and agreeing on the role of the family member in the initial stages of the consultation. Laidsaar-Powell et al. [70], however, highlight the importance of respecting patient preferences for family member involvement, ensuring that patients consent to and support the involvement of their family member.
In dysphagia management, the provision of health information that is complete and unbiased is especially important given the health-related quality of life implications of dysphagia [2, 5]. Both people with dysphagia and their family members report the need for more personalized and practical information regarding dysphagia management [13, 26, 28-31]. Johnson [72] further emphasizes the importance of providing complete and unbiased information on a continuous basis. This, of course, is especially important for people with dysphagia who may not understand or have difficulty following recommendations due to associated cognitive impairments [73], and require their family member to take full responsibility for the decision-making process. In dysphagia management, health information must be both family-centered and holistic in nature, to ensure that the full consequences of dysphagia on the everyday lives of people with dysphagia and their family members are discussed. Previous research has documented the desire of both people with dysphagia and their families to receive more information regarding the potential everyday impacts of dysphagia and how these impacts can be managed [14, 26]. In addition to providing information about the everyday impacts of dysphagia, in order to provide effective FCC, health professionals should also provide information about the role of family members in the management process [74], including issues relating to meal preparation, shopping for textured modified foods, household organization, nutrition, and encouraging their family member with dysphagia to keep eating [26], and importantly, discussion of strategies and resources that may aid them in this role.
Another consideration for clinicians is how this information provided to people with dysphagia and their family members could most effectively inform shared decision making. Shared decision-making is one of the key principles of FCC and involves active participation of both the patient and family in the decision-making process. Kaizer et al. [73] described a shared decision-making model that was used with people with dysphagia and their family members in a rehabilitation hospital setting. Kaizer et al. [73] acknowledged that the use of a family-centered shared decision-making model was important in the management of dysphagia as the success of dysphagia recommendations required considerable cooperation and participation of both people with dysphagia and their family members. Engagement of people with dysphagia and their family in the decision-making process is especially important to ensure that they understand and agree with the recommendations being made. In situations when patients and families feel “forced” to follow a management plan they do not agree with, divisions may develop between family members, hampering positive relations between the patient and family and the health care team [73].
It is clear that in order to promote the best possible outcomes for people with dysphagia, and minimize the third-party disability experienced by family members of people with dysphagia, the provision of more holistic, family-centered approach to dysphagia management is recommended. This chapter has provided some key evidence supporting the use of FCC in other areas of health care, which could readily be applied to services for people with the dysphagia and their families. Some important considerations for the successful implementation of FCC have also been discussed, with concepts from other fields of health care applied to dysphagia rehabilitation.
7. Conclusion
Current research has documented both the medical, psychosocial, and health-related quality of life impacts of dysphagia. In addition, emerging research is also demonstrating the pervasive nature of dysphagia on family members. Though the physiological impacts of dysphagia are generally well recognized and managed, people with dysphagia and their families may also experience significant negative effects on their daily lives including impacts on meal preparation, family dynamics and family mealtimes, social occasions, and psychological effects. Though clinicians generally recognize the importance of family members, many focus their attention on the individual with dysphagia and therefore the effect of dysphagia on family members is rarely assessed or managed. Providing a more holistic and family-centered approach to dysphagia assessment and management, using a framework such as the ICF, may not only assist the family, but may also result in more positive long-term outcomes for people with dysphagia. In the next decade, further research is required to document the effects of dysphagia on the family and to develop new and innovative treatments for family-centered care in dysphagia management.
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Scarinci, Bena Cartmill and Elizabeth C.\nWard",authors:[{id:"172198",title:"Prof.",name:"Elizabeth",middleName:null,surname:"Ward",fullName:"Elizabeth Ward",slug:"elizabeth-ward",email:"liz.ward@uq.edu.au",position:null,institution:{name:"University of Queensland",institutionURL:null,country:{name:"Australia"}}},{id:"172221",title:"Dr.",name:"Rebecca",middleName:"Louise",surname:"Nund",fullName:"Rebecca Nund",slug:"rebecca-nund",email:"r.nund@uq.edu.au",position:null,institution:{name:"University of Queensland",institutionURL:null,country:{name:"Australia"}}},{id:"172291",title:"Dr.",name:"Nerina",middleName:null,surname:"Scarinci",fullName:"Nerina Scarinci",slug:"nerina-scarinci",email:"n.scarinci@uq.edu.au",position:null,institution:null},{id:"172292",title:"Dr.",name:"Bena",middleName:null,surname:"Cartmill",fullName:"Bena Cartmill",slug:"bena-cartmill",email:"bena.cartmill@gmail.com",position:null,institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. The biopsychosocial effects of dysphagia",level:"1"},{id:"sec_3",title:"3. The effects of dysphagia on the family",level:"1"},{id:"sec_3_2",title:"3.1. Managing modified diets and fluids and providing appropriate meals",level:"2"},{id:"sec_4_2",title:"3.2. Influence of dysphagia on family dynamics and social activities",level:"2"},{id:"sec_5_2",title:"3.3. Emotional impacts of dysphagia",level:"2"},{id:"sec_7",title:"4. Third-party disability in dysphagia",level:"1"},{id:"sec_8",title:"5. Strategies used by family members to cope with dysphagia",level:"1"},{id:"sec_9",title:"6. Role of family-centered care in dysphagia management",level:"1"},{id:"sec_10",title:"7. Conclusion",level:"1"}],chapterReferences:[{id:"B1",body:'Sura, L., et al., Dysphagia in the elderly: management and nutritional considerations. 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Children\'s Health Care, 1990. 19(4): 234-241.'},{id:"B73",body:'Kaizer, F., A.M. Spiridigliozzi, and M.R. Hunt, Promoting shared decision-making in rehabilitation: Development of a framework for situations when patients with dysphagia refuse diet modification recommended by the treating team. Dysphagia, 2012. 27(1): 81-87.'},{id:"B74",body:'Wolff, J.L., et al., Going it together: Persistence of older adults’ accompaniment to physician visits by a family companion. Journal of the American Geriatrics Society, 2012. 60(1): 106-112.'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Rebecca L. Nund",address:"r.nund@uq.edu.au",affiliation:'
School of Health and Rehabilitation Sciences, The University of Queensland, St Lucia Campus, Brisbane, Australia
Centre for Functioning and Health Research, Metro South Hospital and Health Services, Brisbane, Australia
'},{corresp:null,contributorFullName:"Nerina A. Scarinci",address:null,affiliation:'
School of Health and Rehabilitation Sciences, The University of Queensland, St Lucia Campus, Brisbane, Australia
Centre for Functioning and Health Research, Metro South Hospital and Health Services, Brisbane, Australia
Speech Pathology Department, Princess Alexandra Hospital, Brisbane, Australia
'},{corresp:null,contributorFullName:"Elizabeth C. Ward",address:null,affiliation:'
School of Health and Rehabilitation Sciences, The University of Queensland, St Lucia Campus, Brisbane, Australia
Centre for Functioning and Health Research, Metro South Hospital and Health Services, Brisbane, Australia
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Sheregii",authors:[{id:"102655",title:"Prof.",name:"Eugen",middleName:null,surname:"Sheregii",fullName:"Eugen Sheregii",slug:"eugen-sheregii"}]},{id:"36191",title:"Effective Reaction Monitoring of Intermediates by ATR-IR Spectroscopy Utilizing Fibre Optic Probes",slug:"effective-reaction-monitoring-of-intermediates-by-atr-ir-spectroscopy-utilizing-fibre-optic-probes",signatures:"Daniel Lumpi and Christian Braunshier",authors:[{id:"109019",title:"Dr.",name:"Christian",middleName:null,surname:"Braunshier",fullName:"Christian Braunshier",slug:"christian-braunshier"},{id:"111798",title:"MSc.",name:"Daniel",middleName:null,surname:"Lumpi",fullName:"Daniel Lumpi",slug:"daniel-lumpi"}]}]}]},onlineFirst:{chapter:{type:"chapter",id:"73562",title:"Surgical Techniques of Multiorgan Procurement from a Deceased Donor",doi:"10.5772/intechopen.94156",slug:"surgical-techniques-of-multiorgan-procurement-from-a-deceased-donor",body:'
1. Introduction
Organ transplantation from deceased donor is the standard technique for treatment of so many diseases which is totally incurable without such complicated surgeries. A deceased donor has multiple solid organs that may be used for transplantation and multidisciplinary approach and delicate coordination between different medical and surgical teams is needed to ensure that these organs are fully functional after retrieval. Heart, lungs, liver, kidneys, pancreas and small bowel are among the most important organs that should be harvested at the same time from one donor and each surgeon who is in charge of such a complicated surgery should be familiar with at least basic techniques of other organs retrieval to prevent any harm to sensitive anatomic components of each organ especially those which are in common between two nearby organs, for example portal vein and celiac trunk (liver and pancreas), abdominal inferior vena cava (liver and kidneys), superior mesenteric artery and vein (pancreas and small intestine), supra-diaphragmatic inferior vena cava (heart and liver), pulmonary artery and veins (heart and lungs). Chairman of the team should be the most expert surgeon who has the longest experience with all aspects of multiorgan procurement surgery. In this chapter we will be discuss the basic aspects of surgical techniques which every transplant surgeon has to know about such an important procedure.
2. Brief history of multiorgan donation
The era of organ transplantation was started successful kidney transplantation in the early 1950s. First organ donation from non-heart-beating donors was associated with successful liver transplantation by Thomas Starzl in 1963 [1]. First rare heart-beating donors without any hope of survival (not living donors) were those who underwent cardiac bypass but not able to detach from the heart-lung machine whose kidneys were used for transplantation before death in 1962 [2]. Next successful transplantation from heart-beating donors were done in 1964 in Sweden and in 1966 in United States from patients with irreversible brain damage under mechanical ventilation [2]. The term “cerebral death” was supposed by Swedish neurosurgeons in 1965 [3]. First series of successful liver transplantations from such “brain death” donors was done by Thomas Starzl in 1967–1968 and Professor Barnard do the first successful heart transplant in the same year from another brain-dead person [2]. At that time Barnard waited for cardiac asystole to prevent any negative debate for “brain death concept” in the community [4]. In the next decade many authorities in all the pioneer countries in transplantation made every effort to legally confirm the brain death patients as a potential donor and at last in 1971 the “Uniform Anatomical Gift Act” in Kansas was approved by the governor as a basis for globalization of legally “brain death concept” [5]. Development of multiple transplant teams in next decade resulted in first multiorgan retrieval procedures from the same donor in the 1980s [6, 7]. First heart-lung transplant was done in 1982 and first long term survived lung transplant alone was done in 1987 [8]. In the same era till the 1990s, successful combined transplantation such as liver combined with small bowel and other more complex multivisceral transplantation was developed by Thomas Starzl and his former fellow Andreas Tzakis [9]. Thanks to all the pioneers’ efforts, now we have a near standard technique for multiorgan procurement from all stable brain-dead donors. Only the availability of all the team members and also the suitability of all the organs and suitable recipients are among the remaining obstacle such a complex procedure and multiorgan donation at the same time is a rule in most experienced transplant centers.
3. Donor management
Ideally, every deceased donor should be completely stable before and during transfer to the operating theater. Central venous pressure should be maintained between 10 and 12 mmHg for better function of abdominal organs but for lung retrieval this pressure should be maintained around 8 mmHg [10]. Systolic blood pressure maintenance over 100 mmHg and mean arterial pressure over 60 mmHg by using inotropes and crystalloid infusion is critical. Dopamine, dobutamine, vasopressin and nor-adrenaline may be used but when heart is being used for transplantation dosage of nor-adrenaline over 0.05 microgram/kg/min may reduce cardiac contractility after transplantation and should be avoided [11]. In such cases insertion of Swan-Ganz catheter is mandatory.
Every effort should be done to maintain PaO2 > 100 mmHg, SpO2 > 95%, PaCO2 between 35 and 40 mmHg and pH between 7.35 and 7.45 by using lung protective strategy including avoidance of excessive intravenous fluids, minimal tidal volume (8–12/minute) and lowest FiO2 [12].
For hormonal management, intravenous infusion of 1000 mg (15 mg/kg) methylprednisolone succinate, insulin (target glucose level of 80–150 mg/dl), vasopressin 0.5–4 U/h) or intranasal desmopressin (1–2 puff every 6 hours) and thyroxine replacement (4 mcg/h) is the standard of treatment to reduce the systemic inflammatory response in these patients and maintaining the hemodynamic stability of them [10].
Urine output is better maintained between 100 and 300 ml/hour to prevent hypo or hypernatremia. Potassium (K+) replacement should be started when serum potassium level is reduced (target K+ level 3.5–4.5 meq/l). Lactated ringer’s solution or half saline solution is the best available fluid for these patients and using colloids such as albumin should be avoided [13].
Body temperature should be maintained over 35.8°C [13] for better cardiac function and prevention of coagulation cascade and hypoxic tissue damage. To reduce cardiac arrhythmias maintaining normal body temperature, hemodynamics, electrolyte, hemoglobin levels over 10 g/dl and minimal use of vasopressors is essential. Calcium, phosphorus and magnesium also should be maintained at physiologic level to prevent cardiac arrhythmias during the surgery [14].
4. Key controversies in the result of multiorgan procurement
We have many unresolved issues about multiorgan procurement surgery that needs more time to answer by the researchers. As the same with other works which are done by a team, expertise of each of the team member and their coordination with other members have a great effect on the final result of the operation. Undoubtedly, multiorgan retrieval may compromise the function of each organ and will be associated with a higher incidence of delicate anatomical structures damage. It may be better to perform all the dissections without any compromise in the circulation of any other organs. Many researchers show that this concern is not completely definite. Even some authors in their prospective and retrospective studies show that multiorgan harvesting may improve each separate organ function [10]. The main factor that affects the final result is the stability of the patient during the operation and the expertise of who is in charge of the whole operation [15]. One study shows that renal anatomical damage is more common when the operation is done by renal team only and if the operation is done by the liver team with experience of more than 50 procurement per year, the final anatomical (artery, vein ureter or capsular) damage will be significantly reduced [16]. In unstable patients, it is the duty of the team leader to determine which organ is more important and is the first priority. Usually in urgent situations, this is the “liver”, because liver transplantation has the only way to cure the hepatic failure without any other treatment option in these patients with an acceptable success rate.
Another concern is that should dissection be done in warm or cold condition and en-bloc or separate organ retrieval is different? In fact, although theoretically the anatomical damage may be reduced if all the delicate dissections are performed in the donor before clamping of the aorta and all the organs retrieved separately, but most studies show that en-bloc retrieval and continuing the dissections after whole body cooling and whole blood evacuation have better results [10]. The rationale for this concept is that complete dissection especially in inexperienced hands is extremely time consuming and may result in end organ ischemia by inducing vasospasm. Using rapid technique is more acceptable for operating room personnel and other members of the team, and this technique that one was used only for unstable donors is now the routine in most transplant centers [10].
Although most centers are reluctant to change their previous successful policies and it is a routine to perform double cannulation (aortic and portal) for dual perfusion of the liver, but nowadays with increased use of the pancreas and small bowel for transplantation, double perfusion may be replaced by the single aortic perfusion as a rule for most deceased donors [10]. With the advent of machine perfusion which used only one system for ex situ perfusion, there is increasingly more doubt about need for double perfusion and most studies shows that arterial perfusion is more important in saving the organ function especially the biliary system [17].
5. Type, volume, and pressure of preservation solution
Historically, blood is the first perfusate that was used for organ preservation [18]. After that, Alexis Carrel reported the first n0n-bood solution named Tyrode’s solution which can preserve cat thyroid tissue viable for 3–21 days [18]. In 1960s hypothermia added to blood or serum for better survival of kidney grafts. Since then, static cold storage (STS) by perfusion of the organs by cold (0–4°C) solutions was accepted as the gold standard for organ preservation till now [18]. Collin’s solution (invented in 1969) and then Euro-Collin’s (1980) were the standard solution for organ preservation for next two decades and at last University of Wisconsin (UW) solution was invented by Belzer in 1985 [19]. This solution is low Na+, high K+ solution like intracellular fluid (ICF) which was the gold standard for organ preservation for at least 2 decades.
Histidine-tryptophan-ketoglutarate (HTK) (low Na+, high K+ with cardioplegic effects) and Celsior (high Na+, low K+) solutions are next preservative fluids which was initially used only for heart transplantation in 1990s which were much cheaper and very soon, UW was replaced by these solutions in all abdominal organ transplantations in some transplant centers [18]. Although, these solutions have lower cost and lower viscosities, but till now, UW is the standard solution for heart transplantation in most centers [20]. IGL-1® (Institute George Lopez-1) liquid is another low viscosity solution which reversed electrolyte concentration compared with UW (K+ 25 meq/l, Na + 120 meq/l) with lower cardiac complication and some centers proved that with the use of this liquid, the results of liver and kidney transplantation will be better.
High K+ concentration of this solution made them unsuitable for lung transplantation because of high risk of pulmonary vasoconstriction [20]. Perfadex® (a low-potassium dextran glucose solution) was invented with characteristics of extracellular fluid for this purpose in late 1980s and since then then is used as the standard preservative for lung transplantation [18].
In multiorgan procurement procedure which is a routine procedure in high volume transplant centers, each team usually used its preferred solution for individual organ transplantation. For example, cardiac and abdominal teams may choose HTK or UW solution but pulmonary team uses Perfadex®, and when a heart-lung transplantation is performed en-bloc in one person, then they should use a cardioplegic solution first and after that Perfadex® for pulmonary preservation. Table 1 shows the characteristics of most popular different preservation solutions which are commercially available now.
Name of the solution
Osmolar characteristic
Major composition
Viaspan® (UW solution, University of Wisconsin solution)
Intracellular
K+ 125 meq/l (prevents the K+ transudation of the cells but may cause vasoconstriction) Na + 29 meq/l Hydroxyethyl starch (HES) (reduce extravasation of the fluids but by increasing the viscosity and RBC aggregation may increase renal damage) Raffinose (prevention of cell swelling after cooling) Glutathione (reduction of oxidative effects of free oxygen radicals) Adenosine (increase ATP levels) Allopurinol (protective effect in ischemia by xanthine oxidase inhibition) Lactobionic acid (prevention of intracellular edema)
HTK®
Extracellular
K+ 9 meq/l Na+ 15 meq/l Histidine (precursor for energy metabolism and buffering effect) Tryptophan (cell membrane stabilization and oxygen free radicals’ removal) α-ketoglutaric acid (primary substrate for anaerobic metabolism) Mannitol (prevents hypothermic cell swelling) Higher volume is needed (6–10 lit) Diastolic cardiac arrest
IGL-1®
Extracellular
Based on UW with reversed Na+/K+ concentration (may reduce cardiovascular complication) K+ 25 meq/l Na+ 120 meq/l Polyethylene glycol (PEG-35) (instead of HES for stabilization of the lipid layer of the cell membrane) Allopurinol (protective effect in ischemia by xanthine oxidase inhibition) Adenosine (increase ATP levels) Raffinose (prevention of cell swelling after cooling) Glutathione (reduction of oxidative effects of free oxygen radicals)
Celsior®
Extracellular
K+ 15 meq/l Na+ 100 meq/l 320–360 mOsm/l (hypertonic) Lactobionic acid (prevention of intracellular edema) Mannitol (prevents hypothermic cell swelling) Histidine (precursor for energy metabolism and buffering effect) Glutathione (reduction of oxidative effects of free oxygen radicals) Glutamate (prevent intracellular flush of calcium)
Plegisol®
Extracellular
K+ 16 meq/l Na+ 110 meq/l Osmolarity of 328 mOsm/l and pH = 7.8. Ca2+ (for prevention of calcium flush and sarcolemmic cracking Phosphate buffer (counteracts the effects of metabolic acidosis). Mg2+ is (myocardial stabilization by inhibition of myosin chain phosphorylation) Suitable only for cardiac transplant
Polysol (PS)
Extracellular
Na+ 120 meq/l K+ 15 meq/l Osmolarity 320 mOsm/l. Polyethylene glycol (PEG-35) (stabilization of the lipid layer of the cell membrane) Phosphate buffer (counteracts the effects of metabolic acidosis). Histidine (precursor for energy metabolism and buffering effect HEPES (buffer of N-(2-hydroxyethyl) piperazine-N-2-ethanesulfonic acid) Glutathione (reduction of oxidative effects of free oxygen radicals) Raffinose (prevention of cell swelling after cooling) Trehalose (cytoprotective effect) Vitamins B1, B2, B3, B4, B5, B6, B7, B8, B9, B12, C, A, D2, E, and K3 21 amino acids (alanine, arginine, asparagine, cysteine, glutamine, glycine, isoleucine, leucine, lysine, methionine, ornithine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine)
Perfadex®
Extracellular
Na+ 138 meq/lit K+ 6 meq/l Osmolarity 292 mOsm/l pH 7.4) Dextran 40 (50 g/l) (maintains fluids in the endovascular space) Glucose (as a source of energy) Phosphate buffer (counteracts the effects of metabolic acidosis) Suitable only for lung preservation
ET-Kyoto
extracellular
Na+ 107 mmol/l K+ 42 meq/l Osmolarity 366 mOsm/l Trehalose (cytoprotective effect) Gluconate (counteract cell swelling) Hydroxyethyl starch (HES) (reduce extravasation of the fluids but by increasing the viscosity and RBC aggregation may increase renal damage) Phosphate buffer (prevents metabolic acidosis) Db-cAMP (cyclic adenosine monophosphate dibutyltin) Nitroglycerine (protect the vascular endothelial cells) N-acetylcysteine (NAC) (antioxidant effect and a free radical scavenger) Approved only for lung transplantation
Table 1.
Characteristics of different popular preservation solutions.
Another dilemma that should be resolved is the rate and pressure of preservative solutions. Perfusion by a cold perfusate in not a physiologic process and most teams accepted the 80–100 cm H2O (1 m gravity pressure) as the acceptable pressure for all organs and 150 cm H2O for aortic infusion [10]. With the advent of machine perfusion, it is shown that target arterial flow of 0.25 mL/minute/g and target v0nous flow of 0.75 mL/minute/g liver tissue and mean arterial and portal venous pressure of 30–50 and 8–10 mmHg, respectively, are the acceptable rates for liver transplantation and these figures could be extrapolated to the multiple abdominal organ retrieval procedure [21]. Higher pressure for portal vein irrigation is definitively deleterious for post-transplant function of the graft. For pancreas transplantation the machine pressure should be maintained between 50 and 70 mmHg but the maximum pressure that is acceptable during deceased donor harvesting is not well-defined, although most researchers suggest that overflow of the irrigation of the pancreas tissue is very harmful to its future function [22].
In the adults, for prevention of micro- and macrovascular thrombosis, the standard dosage of heparin is 300 IU/kg and total volume of UW solution is 2–3 liter through the aortic cannula and 1 lit through the portal vein with a flow rate of 50–100 ml/kg/min for abdominal organ transplantation and another 1 liter for back-table preparation of the liver and at least 20 ml for irrigation of the bile ducts [23]. For lower viscosity solutions such as Celsior, HTK or IGL-1®, total volume of perfusate should increase to 6 liters [23] in order to achieve better irrigation of the total blood volume of the harvested organs. For pediatric donors the dosage of heparin is 500 IU/kg and total volume of perfusate should be around 50 ml/kg [23].
6. Cooling
Peritoneal cooling technique by slush ice is a safe and accepted old method for better organ function. It is a routine in all transplant units to use a perfusion temperature of 0–4°C for flushing all the organs but it is not widely proofed that the use of topical slush ice is really beneficial [24]. One author could prove that retroperitoneal slush ice may improve renal function [25] and another one showed improved islet cell recovery from pancreas grafts by using additional slush ice around the pancreas during the organ procurement [26]. There are so many reports in the literature about successful heart and lung transplantation after using topical ice. Transporting the organs in plastic bags filled with organ preservation solution and putting them into another ice –filled bag or cool box is the standard method of transferring organs between different transplant centers. Topical slush ice should be accepted as a routine until better prospective studies show another method but in all steps of organ procurement, preservation and transferring, it is extremely necessary to prevent organs’ freezing with the use of good preservative solutions and prevention of direct contact of the ice to the tissues after retrieval.
7. Surgical procedure
7.1 General principles
Thomas Starzl and his team are the pioneer of multiple organ harvesting from the deceased donor and the technique that they described has minimal change till now after more than 3 decades [27]. All the procurement procedures have some steps in common:
Anesthesiologist management and use of muscle relaxant if needed
Preparation and drape
Long midline sternal and abdominal incision (with transverse extensions if needed)
Primary evaluation of all the torso organs (with frozen section evaluations when indicated)
Control of the aorta for next step cannulation (abdominal; and thoracic if heart transplantation is planned)
Control of supra-celiac and supra-iliac aorta for clamping (for better irrigation of abdominal organs with lower volume of preservative solutions)
Warm dissection of all the important anatomic structures when indicated and the patient’s hemodynamic is stable (for example portal vein, gastroduodenal artery, base of superior mesenteric artery and vein, renal arteries, veins and ureters, pulmonary artery and veins, bile duct, proximal and distal part of the duodenum, etc.)
Preparation of the femoral, iliac vein or inferior vena cava (between the heart and liver, superior to renal veins, near its pelvic bifurcation) for evacuation of blood at the end of operation.
Full heparinization (300/500 IU/kg)
Cannulation of aorta (abdominal; and thoracic if heart transplantation is planned); and portal vein if the patient is stable (through the superior mesenteric vein; or inferior mesenteric vein if short bowel transplantation is planned or cannulation of superior mesenteric vein is impossible or difficult)
Clamping of supra-celiac, supra-iliac and thoracic aortic arc and beginning of irrigation and evacuation of blood through the previous large controlled veins and filling around of all organs with slush ice at the same time.
Removal of the organs with this order: heart, lung, liver, pancreas, small bowel, kidneys, iliac and other large vessels, tissues with potential use as grafts (pericardium, bones, cartilages, tendons, skin, cornea, …). This order may be changed according to planned transplantations and center expertise.
7.2 Starting the operation
Table 2 shows the checklist for essential pre-requisites of the donor characteristics before starting the operation. The surgical team should confirm that all the data in this checklist is ready and acceptable before starting the operation. Usually in most transplant units, the “liver team” is in charge of the whole operation and the operation is started by the most experienced and self- sufficient surgeon in this team by a long midline incision from jugular notch to symphysis pubis in the stable patient. In unstable patients all the steps of the operation may be omitted and replaced by femoral artery and vein cannulation for cold infusion of the preservative fluid and evacuation of the blood and after that all the dissections should be done after in situ cooling and aortic cross clamping below or above the diaphragm.
Donor eligibility
Informed consent of donation by the next of keen
Brain death confirmation by the authorities
Hemodynamic stability (ideal)
Central venous pressure 10–12 cmH2O
Systolic blood pressure maintenance >100 mmHg and mean arterial pressure >60 mmHg
PaO2 > 100 mmHg, SpO2 > 95%, PaCO2 between 35 and 40 mmHg and pH between 7.35 and 7.45
Urine output between 100 and 300 ml/hour
No electrolyte imbalance
Na+ < 160 and K+ 3.5–4.5 meq/l
Normal Ca2+, Mg2++ and P
Negative viral tests
HBsAg, HCVAb, HIVAb, HTLV-1
No active infection
No malignancy
Normal organ specific function tests
Liver function tests, creatinine, histocompatibility tests results, echocardiography, ECG, angiography, bronchoscopy and Gram stains, chest imaging studies, insulin levels, etc.
Coordination with all the teams involved
Readiness of all the recipients and their surgical team
Availability of all surgical equipment needed
Coordination with transport system
Table 2.
Checklist for donor preparedness before starting the operation.
The time of the starting of the incision must be fully coordinated by all the other team members, coordinators and the in-hospital and out of hospital transport system to decrease the total ischemic time to the lowest possible time. It is better not to transfer the donor to other hospitals and in most countries, it is the procurement team that should go the donor hospital and they should have all the equipment, drugs, preservative solutions, organ bags, cool-boxes and surgical instruments that is essential with themselves. The leader of the team should finally check all the prerequisites of the organ donation operation including informed consent of donation, brain death confirmation (patient identity and certificate of death), important blood tests (especially the blood group and viral tests), previous history (especially history of untreated cancer and previous surgeries) and suitability of the donor just before the operation. Discussion of the steps of the operation with other teams will decrease potential injury to the retrievable organs.
A general physical exam is absolutely necessary because all palpable masses in the unexposed area such as breasts, genitalia, axillary and inguinal regions or any skin lesions which are suspicious for malignancies should be excised for pathologic examination.
Every surgeon has to use his or her maximum delicate surgical art to prevent any harm to any of the transplantable organs. For example, if the donor has previous midline sternotomy incision with potential adhesions of the heart, the thoracic incision should be delayed until all abdominal dissections are completed. Sternum may be incised by Gigli’s saw or Stryker® sternal saw if available. After incision, complete hemostasis of all cutting surfaces is essential to prevent obscuring bleeding and suitable retractors such as large Finochietto retractors are placed for maximum exposure of the organs. All the organs should be explored for potential contraindications for donation such as congenital anomalies, malignancies or severe infective processes such as colon perforation or peritonitis.
7.3 Dissection of abdominal organs and large vessel cannulation
Every disturbing adhesion from previous surgeries should be released first to prevent jeopardizing the bowel wall. Superior mesenteric vein is dissected and controlled in the root of mesentery just to the right side of the Treitz ligament and the inferior mesenteric vein in the edge of this ligament. Cephalad retraction of the transverse mesocolon and caudal retraction of small bowel will better expose these two anatomic landmarks. After that, abdominal aorta and inferior vena cava (IVC) are fully exposed and controlled for cannulation by a complete right medial rotation of abdominal viscera from pelvic area till the infra-duodenal area superior to both renal veins. This step has to be done with caution to find all accessory renal arteries and prevent any inadvertent injury to lumbar arteries or veins which will result in uncontrollable or disturbing bleeding. If the distal aorta is not cannulable, the iliac arteries can be used instead. Inferior mesenteric artery (IMA) can be ligated and both ureters can be mobilized at this step but without any trauma to the tissues common between the ureters and genital veins.
Lesser sac is entered through the gastrohepatic ligament with caution not to injure potential left accessory hepatic artery. Left lateral segment of the liver is taken down from the diaphragm and supra-celiac aorta is exposed by blunt dissection of diaphragmatic crura and setting aside the abdominal esophagus and then controlled by an umbilical tape. If such dissections are impossible due to previous adhesions or any other reason, then thoracic aorta should be controlled in the left hemithorax just above the diaphragm and anterior to the lower thoracic vertebra.
At this stage, if “rapid flush technique” is chosen due to patient’s instability, the operation is ended by full heparinization and aortic and portal cannulation, clamping the aorta and cutting the abdominal or infra-atrial IVC for blood evacuation along with the infusion of the preservative solution and covering all the viscera by slush ice.
If the patient is stable further dissections will be done. Bile duct is transected above the duodenum and flushed with 20 ml of cold normal saline. Cholecystectomy is performed. Gastroduodenal artery is explored in upper border of pancreas. If pancreas is suitable for transplantation, duodenum is prepared just next to the pylorus and after the pancreas uncinate process, posterior to transverse colon for transection at the end of operation and superior mesenteric artery is controlled just above the renal arteries root anterior to aorta. The cardiac team is now can come into the operation field.
7.3.1 Tips and tricks
In patients with history of heart surgery or median sternotomy, thoracic incision should be postponed till all the abdominal dissections and cannulation of the great vessels have been finished.
In patients with history of previous abdominal operations, incision should be started as far as possible from the site of previous incision to prevent bowel perforation.
In fatty donors, it is better to perform superior or inferior mesenteric vein dissections, because after full Kocherization and right medial visceral rotation, finding the mesenteric vein will be very difficult.
If during each step of the dissections, any vascular damage is encountered, it is better to repair it with fine sutures only if the location of the damage is easily found and repairable. In other cases, no attempt should be done, because it is time consuming and may cause further damage to critical organs.
During the cannulation of the aorta, the cannula should not be advanced above the celiac artery. Clamping the supra-celiac aorta at the end of the procedure will occlude the cannula and perfusion of the preservative solutions is stopped. All cannulas should have side holes for faster infusion of the solutions.
Unnecessary organ manipulations should be avoided to prevent vasoconstriction. In stable patients, some urologists insisted on postponing the rest of the operation when no urine is noted after ureteral transection.
7.4 Preparation of the heart
In stable donors, after the liver surgeon prepares all prerequisites in the abdomen the heart and/or lung team will welcome to the operation field. All thoracic lymphatic regions must be accurately inspected for signs of occult malignancies such as metastasis or lymphoma and if needed biopsy should be done and sent for frozen section pathologic examination. Thymus gland should be resected first and pericardium is opened longitudinally and fixed to the edges of transected sternum in both sides. Intraoperative cardiac evaluation includes inspection for: signs of previous pericarditis, hematoma or ecchymosis (resulted from previous cardiopulmonary resuscitation), any cardiac anomalies, dyskinesia, scars, contusions, calcification of ascending aorta and coronary arteries, size of the great vessels and heart chambers. At the same time, the inotrope dosage should be reduced by the anesthesiologist to ensure that cardiac contractility is good enough without need of the inotropes. If there is any sign of right heart overloud immediate diuresis by furosemide and reducing the central venous pressure by avoiding any intravenous infusion of crystalloids is mandatory. All the data should transfer immediately to the recipient team so they can make decision on starting the recipient operation.
The window between ascending aorta and pulmonary trunk is opened and controlled by an umbilical tape. Superior and inferior vena cava is encircled with caution not to harm the sinoatrial region or jeopardize the pulmonary veins. For cardioplegic injection at the end of preparation a cannula should be inserted and the arc of aorta should be prepared for clamping before the origin of the innominate artery.
7.5 Preparation of the lungs
Both pleural spaces should be opened at this stage. Lungs are inspected for bullae, contusions, atelectasis, pneumonia and occult tumors. Tracheal tube is disconnected and both lungs are deflated transiently and then inflated again by a pressure of 15–30 cmH2O to better detect the pulmonary compliance (so called “collapse test”) [28, 29]. Usually, most of the vascular dissections were done previous by the heart team including: separation of the pulmonary trunk and right pulmonary artery from posterior wall of the ascending aorta and superior vena cava, and opening the window between the lower right pulmonary vein and intrapericardial IVC (so called “oblique sinus”). The left innominate vein and artery is controlled by umbilical tape to expose the main trachea by retracting them toward the right and left, respectively. The azygous vein should be ligated at this stage to prevent rupture and bleeding. After inserting the cardioplegic cannula in the root of aorta and cannula should be inserted near the bifurcation of the pulmonary trunk for infusion of prostaglandin E1 and Perfadex for lung procurement at the end of all other organs’ retrieval.
7.6 Common steps at the end of the procedure
When all dissections were done according to patient’s stability and the retrievable organs prepared, great vessels’ cannulation is done after full heparinization. The aorta is clamped at two levels: sub- or supra- diaphragmatic and at the end of ascending aorta. Blood evacuation is started by cutting the IVC just inferior to the right atrium or if dissections at this level is impossible, in the abdomen above the iliac vessels. Infusion of the cold preservatives (with cardioplegic effect if heart is being retrieved for transplantation) is started and supporting by the anesthesiologist is finished and the “definitive death” is announced. At the same time immersion of all the retrievable organ by slush ice should be accomplished. If lung procurement was programmed, infusion of Perfadex should be started at the same time and the pulmonary blood should be evacuated by cephalad retraction of the heart and incision of the left atrium between the two inferior pulmonary veins just below the Waterson’s groove or “sulcus terminalis”.
Infusion is continued till all the viscera are exsanguinated. Usually 2–3 lit of infusate through abdominal aorta, 1 lit through the portal vein, 1 lit for ascending aorta and 50 ml/kg of Perfadex is enough for complete blood evacuation. The superior mesenteric artery has to be ligated at this time for prevention of pancreas overperfusion which will severely affect graft function [30, 31]. If small intestinal retrieval is programmed, this step is forbidden, and portal perfusion should be omitted as well or performed through the IMV and only the aorta is perfused [30].
All the organs will be transferred after retrieval to an organ bag full of cold preservative and irrigated again if necessary. This bag should be packed and inserted to another bag filled with cold saline and again in the third bag full of slush ice and then in the cool box for transferring to the recipient ward or hospital. Sometimes especially when the transfer time is long or the donor is marginal the transplant team may decide to use cold or warm perfusion machines for better preservation of the organ.
7.7 Procurement of each organ
7.7.1 Heart and lung
Heart is easily retrieved by transecting the great vessels but this transection should be done step by step to prevent hematoma formation and injury to the vital parts especially the sinus node and pulmonary artery. When all the blood evacuated through the IVC incision, pericardium should be irrigated by cold saline at all steps to prevent warming. Cardioplegic cannula is removed. Aorta is cut just below the clamp, and SVC and IVC completely transected. The heart is gently pulled upward and inferior and superior pulmonary veins are divided one by one an at last the pulmonary trunk will be cut just at its bifurcation to remove the heart.
If the heart-lung complex is planned to be transplanted to one person, all these dissections should be avoided. The cardioplegia and pneumoplegia and prostaglandin E solutions is infused through the aortic and pulmonary artery catheters. Blood is evacuated from heart by incising the IVC and the returned blood from the lungs is evacuated through a small incision in left atrial appendages. Only the ascending aorta is transected before the innominate artery origin and the trachea is stapled after inflation of both lungs and removal of the endotracheal tube. The SVC is transected and origin of azygous vein is transligated and at last the heart -lung complex is procured by releasing their attachments to the mediastinum.
If transplantation of the lungs alone is planned, cardiac team should be left posterior wall of the left atrium intact in line with for pulmonary veins. After removing the heart, the posterior wall of left atrium and its surrounding pericardium is dissected from posterior mediastinum including the esophagus and descending and this avascular plate is continued till both lungs are released bilaterally. Small volume ventilation should be continued till all the dissections are completed and at the end and after complete inflation, the endotracheal tube is removed and trachea is stapled to extract both lungs outside the thoracic cavity.
7.7.2 En bloc retrieval of abdominal organs
The fasted way to retrieval of abdominal organs is en bloc resection. Sometimes the time is very important for the harvesting team for example when the organs will transfer to another city by a commercial flight. In some cases, all abdominal organs should be transplanted to one recipient, for example a recipient with cirrhosis due to complete portal and superior mesenteric vein thrombosis needs a simultaneous liver-small intestinal transplantation [32]. In such cases all abdominal organs have to be procured en bloc.
According to the organs being retrieved for multivisceral transplantation, there are several ways to do such procedure [30, 33]. After the heart and/or lung team retrieved their organs, the abdominal team can complete their operation. Amphotericin B, metronidazole and sometimes diluted povidone iodine is instilled into the duodenum by a nasoduodenal tube [31]. For better exposure and preventing of bowel content spillage, usually the stomach and colon should be resected and discarded first, by stapling the esophagogastric and gastroduodenal junction and also the ileocecal and colorectal junction and transecting their vasculature. Then the sub-diaphragmatic aorta which was previously controlled is transected. All diaphragmatic adhesions of the liver and spleen are released and the infra-atrial IVC is separated with a patch of pericardium and surrounding tissue around it. At last, all the organs including aorta, IVC, liver, pancreas, spleen and small intestine are swept up of posterior abdominal wall and lumbar vertebrae and muscles and the procurement is completed by transecting the ureters at pelvic rim and iliac vessels just before entering the femoral canal [3]. All the dissections in this step should be with extreme gentleness not to push or pull any of the vital structures.
7.7.3 Liver
In most centers liver and kidneys are the only organs used for transplantation especially when the donor has a high body mass index or marginal for any cause (unstable, diabetic, hypertensive, old age, etc.). For retrieval, these steps are necessary: transecting the infra-atrial IVC with a rim of pericardium and diaphragm, taking down the falciform, right and left triangular ligaments from the diaphragm, transecting the gastroduodenal (GD) and right gastric arteries and following the artery till the origin of the celiac artery by complete dissection of diaphragmatic crura.
If pancreas is not suitable for transplantation, dissection of the portal vein should be continued by transection of the pancreas neck anterior to SMV and swiping up the head of pancreas and duodenum to the right and the tail of pancreas to the left to expose the base of the SMV and SMA anterior to aorta. Then the origins of celiac and superior mesenteric arteries are separated from the aorta with a common Carrel patch. Replaced or accessory right and left hepatic arteries must not be jeopardized or pulled in any way and remained attached to their main large paternal vessel. Splenic vein and distal SMV SMA is transected at the level of uncinate process. IVC is transected above the renal veins’ origin. Now after complete releasing of all inflow and outflow structures, the liver can be removed easily by final releasing it from the posterior wall and transferred to an organ bag and irrigated by another 1 lit of preservative solution without direct contact to ice.
If pancreas is transplantable all the dissections should be limited to upper border of the pancreas and portal vein and GD artery transected just above the duodenum and the SMV, SMA and splenic artery attachment to the pancreas be remained intact. Sometimes liver and pancreas will be removed in continuity and separated from each other in the time of back table preparation [30].
7.7.4 Small intestine
If gastrectomy and total colectomy were done previously with good hemostasis of the vessels, removal of the small intestine is relatively easy and straight forward. As I told before, at the start of the operation for exposure of the aorta and IVC, small intestine is gently wrapped in a lap-sponge and pull cephalad to detach all the mesentery in an avascular plain from ileum to the Treitz. At the end of operation and evacuation of all the blood by aortic and IMV irrigation, the small intestine only attached to the body superior mesenteric pedicle containing SMA and SMV. Duodenojejunal and ileojejunal junction was previously cut by staples and the whole graft can be removed only by cutting the SMA and SMV at this time. If small intestine is decided to transplant separately, it is necessary to remove it before liver and pancreas but if a multivisceral transplant is planned for the recipient, any dissection around the SMV and SMA at the root of mesentery is forbidden and IMV should be used for cannulation of the portal vein [30, 32, 33].
7.7.5 Pancreas
As I discussed previously, pancreas usually is procured along with the liver and separated from it in back table procedure. If the surgeon decided to retrieve each organ individually, then after removing the stomach by stapling of duodenum after pylorus, portal vein, GD and splenic arteries are cut at the upper border of pancreas. Another staple is used for transection of the duodenum between D2 and D3 area at the level of uncinate process, and the SMV and SMA and origin of mesentery is transected by another vascular staple. The IMV is ligated the lower border of pancreas is separated from left renal vein and the left kidney. The previously extended Kocherization is continued toward the left to separate the duodenum from the vertebra, aorta and posterior wall of the abdomen and at last the attachments of the spleen are released and procurement of the duodenum-pancreas-spleen is completed [30, 34].
7.7.6 Kidneys
Kidneys are the last organs that will be removed. They may be procured en-bloc in line with aorta and IVC when both of them are programmed to transplanted to one person (for example from a pediatric or marginal donor for an adult recipient, or when we encounter with a horseshoe kidney with multiple renal arteries and veins) or retrieved separately. For separation, IVC is transected transversely just above the renal vein origins and then incised longitudinally to explore for possible multiple renal veins. All renal veins should be separated with a common patch of IVC. Separation of renal veins should be done with caution not to injure the renal arteries which run posterior to veins especially accessory undefined renal arteries. Ureters (sometimes double or rarely multiple) are completely separated from the surrounding tissues and transected distally in the pelvic rim, but the window tissues between kidneys and ureters and also between the ureters and gonadal veins should remain intact to prevent ischemia and future contracture or anastomotic failure. Renal arteries are exposed by longitudinal incision of the aorta to find multiple branches from inside the aorta and retrieval with a common patch. Rarely an accessory branch may originate from the iliac arteries or the other side of the aorta. It is better not to jeopardize such branches but the kidney transplant team should be capable of back-table microvascular reconstruction of several arterial branches in such cases. Left adrenal vein is ligated and transected as well.
After complete separation of all arterial and venous branches, kidneys are retrieved by medial to lateral movement by the surgeon with extreme caution not to over-retract these branches and induce intimal rupture. Also rupture of renal capsule has to be prevented by using sharp dissections specially in older marginal donors. It is better to perform these dissections outside the perirenal fatty tissues to prevent such inadvertent injuries.
8. Machine perfusion
Full discussion about the machine perfusion is beyond the scope of this chapter. Ideally all the organs retrieved should be transplanted immediately or as soon as possible in the same center of the organ procurement. But this is impossible, irrational or illegal in many situations. The donor operation can be easily done in a small rural hospital without any transplant facilities in unstable patients. In such cases transferring the organ to other hospitals is the rule. Another such circumstances is, when histocompatibility (for example for kidney and pancreas), or duration of stay in the waiting list is an important matter for decision making, and transplantation in the same center in such cases is both irrational and illegal. In marginal donors and in cases of donation after cardiac death (DCD), it is very important for the transplant surgeon to predict functionality of the organs. In all such situation, machine perfusion is the best way to know the organ function and increase the time of organ viability before final in vivo reperfusion.
In contrast to static cold storage (SCD) which we discussed in all sections of this chapter, dynamic perfusion techniques use a perfusate for active perfusion of the organs in situ (en vivo) or ex situ (ex vivo) [35]. For example, normothermic regional perfusion (NRP) is an en vivo method for reconditioning organs for DCD by restoring oxygenated blood flow to the organs before procurement. For such purpose, we need a sophisticated Extracorporeal Machine Oxygenation (ECMO) technology, which is not available in most centers. In contrast to this technique, ex vivo machine perfusion is used after organ recovery specially for kidneys and liver. It may be used in a hypothermic (hypothermic machine perfusion or HMP) or normothermic (normothermic machine perfusion or NMP) milieu. For kidney grafts, it is shown that HMP reduced significantly delayed graft function both after DCD and donation after brain death in marginal donors [35]. NMP is an established method for confirming the functionality of marginal liver grafts by showing the function of the graft and preventing ischemic cholangiopathy and it is shown that this method reduced the discard rate by 50% [36]. The results are promising for pancreas and small intestine as well. Machine perfusion of the heart is an essential step in all cases of DCD and for lungs it is essential for uncontrolled DCD cases [37]. In my opinion, future of organ transplantation from marginal donors is in the hand of the engineers who invents better, cheaper and more efficient and reliable machines with simpler use by transplant surgeons, but at these days use of these techniques should be limited to high income countries with an extensive network of transplantation services all around their territories.
9. Conclusion
Multiorgan procurement from the same donor is the combination of the art of cooperation between several medical team with different expertise level. If any of the team member makes any mistake during such sophisticated procedure all other organs will be jeopardized and the life of many recipients will be in danger. It is the task of the team leader to manage such problems before they become irreversible, and this will be impossible without basic knowledge of all aspects of the other organ’s retrieval by all other surgeons who is in charge of their organ.
Acknowledgments
This article is supported by Vice chancellor of research, Tabriz University of Medical Sciences, Tabriz, Iran. It is dedicated to my mentor great transplant surgeon Dr. Seyyed Ali Malekhosseini, the father of visceral transplant surgery in Iran.
Conflict of interest
There is no conflict of interest to declare.
\n',keywords:"organ transplantation, multiorgan procurement, deceased donor, surgery, technique",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/73562.pdf",chapterXML:"https://mts.intechopen.com/source/xml/73562.xml",downloadPdfUrl:"/chapter/pdf-download/73562",previewPdfUrl:"/chapter/pdf-preview/73562",totalDownloads:79,totalViews:0,totalCrossrefCites:0,dateSubmitted:"July 1st 2020",dateReviewed:"September 22nd 2020",datePrePublished:"October 12th 2020",datePublished:null,dateFinished:null,readingETA:"0",abstract:"Solid organ transplantation is now the standard treatment for many types of diseases and using a standard surgical technique for organ procurement from the deceased donors is an important step in preventing complications after such complicated procedures. In most centers, retrieval of heart, lungs, liver, kidneys, small bowel, pancreas and other organs is done at the same time by different surgeons under supervision by a team leader who is most familiar with at least basic steps of surgical technique of procurement of all the solid organs. Each transplant surgeon, regardless of his or her sub-specialty, has to know how to prepare and dissect the delicate anatomical structures which are in common between the two adjacent organs for example portal vein (liver-pancreas), superior mesenteric vein (pancreas-small bowel), abdominal inferior vena cava (liver-kidneys), supra-diaphragmatic inferior vena cava (liver-heart) and pulmonary artery-veins (heart-lungs). This needs a multidisciplinary approach by the most experienced members of the transplant team to decrease the warm ischemic time of the organs without any harm to them by better coordination between all the surgeons. In this, chapter we briefly describe the multiorgan retrieval procedure in a deceased donor, and we hope that following these instructions results in better quality of the procured organs without jeopardizing their vital anatomical structures.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/73562",risUrl:"/chapter/ris/73562",signatures:"Farzad Kakaei",book:{id:"9524",title:"Organ Donation and Transplantation",subtitle:null,fullTitle:"Organ Donation and Transplantation",slug:null,publishedDate:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/9524.jpg",licenceType:"CC BY 3.0",editedByType:null,editors:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"26626",title:"Dr.",name:"Farzad",middleName:null,surname:"Kakaei",fullName:"Farzad Kakaei",slug:"farzad-kakaei",email:"fkakaei@yahoo.com",position:null,institution:{name:"Tabriz University of Medical Sciences",institutionURL:null,country:{name:"Iran"}}}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Brief history of multiorgan donation",level:"1"},{id:"sec_3",title:"3. Donor management",level:"1"},{id:"sec_4",title:"4. Key controversies in the result of multiorgan procurement",level:"1"},{id:"sec_5",title:"5. Type, volume, and pressure of preservation solution",level:"1"},{id:"sec_6",title:"6. Cooling",level:"1"},{id:"sec_7",title:"7. Surgical procedure",level:"1"},{id:"sec_7_2",title:"7.1 General principles",level:"2"},{id:"sec_8_2",title:"7.2 Starting the operation",level:"2"},{id:"sec_9_2",title:"7.3 Dissection of abdominal organs and large vessel cannulation",level:"2"},{id:"sec_9_3",title:"7.3.1 Tips and tricks",level:"3"},{id:"sec_11_2",title:"7.4 Preparation of the heart",level:"2"},{id:"sec_12_2",title:"7.5 Preparation of the lungs",level:"2"},{id:"sec_13_2",title:"7.6 Common steps at the end of the procedure",level:"2"},{id:"sec_14_2",title:"7.7 Procurement of each organ",level:"2"},{id:"sec_14_3",title:"7.7.1 Heart and lung",level:"3"},{id:"sec_15_3",title:"7.7.2 En bloc retrieval of abdominal organs",level:"3"},{id:"sec_16_3",title:"7.7.3 Liver",level:"3"},{id:"sec_17_3",title:"7.7.4 Small intestine",level:"3"},{id:"sec_18_3",title:"7.7.5 Pancreas",level:"3"},{id:"sec_19_3",title:"7.7.6 Kidneys",level:"3"},{id:"sec_22",title:"8. Machine perfusion",level:"1"},{id:"sec_23",title:"9. 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J Thorac Dis. 2018; 10(Suppl 8): S910-S923. doi:10.21037/jtd.2018.02.85'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Farzad Kakaei",address:"fkakaei@yahoo.com",affiliation:'
Department of Surgery, Faculty of Medicine, Tabriz University of medical sciences, Tabriz, Iran
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Along with direct prion diseases, such as bovine rabies and Creutzfeldt-Jakob disease in humans, a great number of neurodegenerative disorders associated with the formation of aggregates through the prion mechanism are revealed. These disorders include Alzheimer’s and Parkinson’s diseases, amyotrophic lateral sclerosis, Huntington disease, and mucoviscidosis, some types of diabetes and hereditary cataracts. The listed diseases are caused by transition of a “healthy” protein or peptide molecule from the native conformation to a very stable “pathological” form. In this case, molecules in the “pathological” conformation aggregate specifically, forming amyloid fibrils that can multiply infinitely. An important result of studying the molecular mechanisms of prion diseases and different proteinopathies, associated with the formation of pathological aggregations by the prion mechanism, is the discovery of protein chain regions responsible for their aggregation. The ability to regulate aggregation (fibrillation) of proteins can be the focal tool for the drug development. Herein by the example of 29 RNA-binding proteins with prion-like domains, we demonstrate what role the amino acid repeats in prion-like domains can play. For these proteins, quite different repeats are revealed in the disordered part of the protein chain predicted with bioinformatics methods. Ten proteins of the 29 RNA-binding proteins are involved in the development of some diseases. The prion-like domains of FUS, TAF15, and EWS are critical for the aggregation of proteins associated with human neurodegenerative diseases. Proteins of this family are involved not only in neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), Huntington disease, spinocerebral ataxy, and dentatorubral pallidoluysian atrophy, but also in the formation of human mixoid liposarcoma. It can be suggested that the presence of a great number of repeats in prion-like domains of RNA-binding proteins can accelerate the formation of a dynamic beta-structure and pathological aggregates, which are crucibles of amyotrophic lateral sclerosis (ALS) pathogenesis.",signatures:"Oxana V. Galzitskaya",authors:[{id:"181238",title:"Dr.",name:"Oxana",surname:"Galzitskaya",fullName:"Oxana Galzitskaya",slug:"oxana-galzitskaya",email:"ogalzit@vega.protres.ru"}],book:{title:"Update on Amyotrophic Lateral Sclerosis",slug:"update-on-amyotrophic-lateral-sclerosis",productType:{id:"1",title:"Edited Volume"}}},{title:"Kinetics of Amyloid Formation by Different Proteins and Peptides: Polymorphism and Sizes of Folding Nuclei of Fibrils",slug:"kinetics-of-amyloid-formation-by-different-proteins-and-peptides-polymorphism-and-sizes-of-folding-n",abstract:"Aggregation of peptides and proteins into amyloid structure is one of the most intensively studied biological phenomena at the moment. To date, there is no developed theory that would allow one to determine what kind of mechanism presents in the given experiment on the basis of aggregation kinetic data. Debates concerning the mechanism of the amyloid fibrils formation and, in particular, the size of the amyloidogenic nucleus are still going on. We created such a theory on the basis of the kinetics of amyloid aggregates formation. In the presented chapter, theoretical and experimental approaches were employed for studding the process of amyloid formation by different proteins and peptides. The current kinetic models described in this chapter adequately describe the key features of amyloid nucleation and growth.",signatures:"Oxana V. Galzitskaya, Nikita V. Dovidchenko and Olga M.\nSelivanova",authors:[{id:"181238",title:"Dr.",name:"Oxana",surname:"Galzitskaya",fullName:"Oxana Galzitskaya",slug:"oxana-galzitskaya",email:"ogalzit@vega.protres.ru"},{id:"185779",title:"Dr.",name:"Olga",surname:"Selivanova",fullName:"Olga Selivanova",slug:"olga-selivanova",email:"seliv@vega.protres.ru"},{id:"185780",title:"MSc.",name:"Nikiat",surname:"Dovidchenko",fullName:"Nikiat Dovidchenko",slug:"nikiat-dovidchenko",email:"bones@phys.protres.ru"}],book:{title:"Exploring New Findings on Amyloidosis",slug:"exploring-new-findings-on-amyloidosis",productType:{id:"1",title:"Edited Volume"}}}],collaborators:[{id:"86115",title:"Dr.",name:"Cristina",surname:"Cereda",slug:"cristina-cereda",fullName:"Cristina Cereda",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Fondazione Istituto Neurologico Nazionale Casimiro Mondino",institutionURL:null,country:{name:"Italy"}}},{id:"91667",title:"Dr.",name:"Seiichi",surname:"Nagano",slug:"seiichi-nagano",fullName:"Seiichi Nagano",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"National Center of Neurology and Psychiatry",institutionURL:null,country:{name:"Japan"}}},{id:"180809",title:"Dr.",name:"Sebastiano",surname:"Cavallaro",slug:"sebastiano-cavallaro",fullName:"Sebastiano Cavallaro",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"National Research Council",institutionURL:null,country:{name:"Italy"}}},{id:"181389",title:"Ph.D.",name:"Maria Teresa",surname:"Gonzalez Garza",slug:"maria-teresa-gonzalez-garza",fullName:"Maria Teresa Gonzalez Garza",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"181934",title:"Ph.D. Student",name:"Giovanna",surname:"Morello",slug:"giovanna-morello",fullName:"Giovanna Morello",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"182162",title:"Prof.",name:"Yves",surname:"Lecarpentier",slug:"yves-lecarpentier",fullName:"Yves Lecarpentier",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"182413",title:"Dr.",name:"Toshiyuki",surname:"Araki",slug:"toshiyuki-araki",fullName:"Toshiyuki Araki",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"National Center of Neurology and Psychiatry",institutionURL:null,country:{name:"Japan"}}},{id:"185727",title:"Dr.",name:"Alexandre",surname:"Vallée",slug:"alexandre-vallee",fullName:"Alexandre Vallée",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"185728",title:"Dr.",name:"Francesca Luisa",surname:"Conforti",slug:"francesca-luisa-conforti",fullName:"Francesca Luisa Conforti",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"185729",title:"Mr.",name:"Antonio Gianmaria",surname:"Spampinato",slug:"antonio-gianmaria-spampinato",fullName:"Antonio Gianmaria Spampinato",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null}]},generic:{page:{slug:"partnerships",title:"Partnerships",intro:"
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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OASPA
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STM
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COPE
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Creative Commons
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iThenticate
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OASPA
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The Open Access Scholarly Publishers Association (OASPA) was established in 2008 to represent the interests of Open Access (OA) publishers globally in all scientific, technical and scholarly disciplines. Its mission is carried out through exchange of information, the setting of standards, advancing models, advocacy, education, and the promotion of innovation.
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STM
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The International Association of Scientific, Technical and Medical Publishers (STM) is the leading global trade association for academic and professional publishers. As a member, IntechOpen has not only made a commitment to STM's Ethical Principles.
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COPE
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The Committee on Publication Ethics (COPE) provides advice to editors and publishers on all aspects of publication ethics and, in particular, how to handle cases of misconduct in research and publication. IntechOpen has been a member of COPE since 2013 and adheres to the COPE Code of Conduct and Best Practice Guidelines, ensuring that we maintain the highest ethical standards.
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Creative Commons
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Creative Commons (CC) is a nonprofit organization that enables the sharing and use of creativity and knowledge through free legal tools. IntechOpen uses the CC BY 3.0 license for chapters, meaning Authors retain copyright and their work can be reused and adapted as long as the source is properly cited and Authors are acknowledged.
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Crossref
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Crossref is the official Digital Object Identifier (DOI) Registration Agency for scholarly and professional publications with a goal of making scholarly communications more effective. IntechOpen deposits metadata and registers DOIs for all content using the Crossref System. IntechOpen also deposits its references and uses the Crossref Cited-by service that enables researchers to track citation statistics.
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Altmetric and Dimensions from Digital Science
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Digital Science is a technology company serving the needs of scientific and research communities at key points along the full cycle of research. They support innovative businesses and technologies that make all parts of the research process more open, efficient and effective. IntechOpen integrates tools such as Altmetric to enable our researchers to track and measure the activity around their academic research and Dimensions, to ease access to the most relevant information and better understand and analyze the global research landscape.
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CLOCKSS
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CLOCKSS preserves scholarly publications in original formats, ensuring that they always remain available and openly accessible to everyone.
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Counter
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COUNTER provides the Code of Practice that enables publishers and vendors to report usage of their electronic resources in a consistent way. This enables libraries to compare data received from different publishers and vendors.
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DORA
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DORA is a worldwide initiative covering all scholarly disciplines which recognizes the need to improve the ways in which the outputs of scholarly research are evaluated and seeks to develop and promote best practice. To date it has been signed by over 1500 organizations and around 14,700 individuals.
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iThenticate
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Enago
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SPi Global
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Amazon
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DHL
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I am also a member of the team in charge for the supervision of Ph.D. students in the fields of development of silicon based planar waveguide sensor devices, study of inelastic electron tunnelling in planar tunnelling nanostructures for sensing applications and development of organotellurium(IV) compounds for semiconductor applications. I am a specialist in data analysis techniques and nanosurface structure. I have served as the editor for many books, been a member of the editorial board in science journals, have published many papers and hold many patents.",institutionString:null,institution:{name:"Sheffield Hallam University",country:{name:"United Kingdom"}}},{id:"54525",title:"Prof.",name:"Abdul Latif",middleName:null,surname:"Ahmad",slug:"abdul-latif-ahmad",fullName:"Abdul Latif Ahmad",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"20567",title:"Prof.",name:"Ado",middleName:null,surname:"Jorio",slug:"ado-jorio",fullName:"Ado Jorio",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universidade Federal de Minas Gerais",country:{name:"Brazil"}}},{id:"47940",title:"Dr.",name:"Alberto",middleName:null,surname:"Mantovani",slug:"alberto-mantovani",fullName:"Alberto Mantovani",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"12392",title:"Mr.",name:"Alex",middleName:null,surname:"Lazinica",slug:"alex-lazinica",fullName:"Alex Lazinica",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/12392/images/7282_n.png",biography:"Alex Lazinica is the founder and CEO of IntechOpen. After obtaining a Master's degree in Mechanical Engineering, he continued his PhD studies in Robotics at the Vienna University of Technology. Here he worked as a robotic researcher with the university's Intelligent Manufacturing Systems Group as well as a guest researcher at various European universities, including the Swiss Federal Institute of Technology Lausanne (EPFL). During this time he published more than 20 scientific papers, gave presentations, served as a reviewer for major robotic journals and conferences and most importantly he co-founded and built the International Journal of Advanced Robotic Systems- world's first Open Access journal in the field of robotics. Starting this journal was a pivotal point in his career, since it was a pathway to founding IntechOpen - Open Access publisher focused on addressing academic researchers needs. Alex is a personification of IntechOpen key values being trusted, open and entrepreneurial. Today his focus is on defining the growth and development strategy for the company.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"19816",title:"Prof.",name:"Alexander",middleName:null,surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/19816/images/1607_n.jpg",biography:"Alexander I. Kokorin: born: 1947, Moscow; DSc., PhD; Principal Research Fellow (Research Professor) of Department of Kinetics and Catalysis, N. Semenov Institute of Chemical Physics, Russian Academy of Sciences, Moscow.\r\nArea of research interests: physical chemistry of complex-organized molecular and nanosized systems, including polymer-metal complexes; the surface of doped oxide semiconductors. He is an expert in structural, absorptive, catalytic and photocatalytic properties, in structural organization and dynamic features of ionic liquids, in magnetic interactions between paramagnetic centers. The author or co-author of 3 books, over 200 articles and reviews in scientific journals and books. He is an actual member of the International EPR/ESR Society, European Society on Quantum Solar Energy Conversion, Moscow House of Scientists, of the Board of Moscow Physical Society.",institutionString:null,institution:{name:"Semenov Institute of Chemical Physics",country:{name:"Russia"}}},{id:"62389",title:"PhD.",name:"Ali Demir",middleName:null,surname:"Sezer",slug:"ali-demir-sezer",fullName:"Ali Demir Sezer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62389/images/3413_n.jpg",biography:"Dr. Ali Demir Sezer has a Ph.D. from Pharmaceutical Biotechnology at the Faculty of Pharmacy, University of Marmara (Turkey). He is the member of many Pharmaceutical Associations and acts as a reviewer of scientific journals and European projects under different research areas such as: drug delivery systems, nanotechnology and pharmaceutical biotechnology. Dr. Sezer is the author of many scientific publications in peer-reviewed journals and poster communications. Focus of his research activity is drug delivery, physico-chemical characterization and biological evaluation of biopolymers micro and nanoparticles as modified drug delivery system, and colloidal drug carriers (liposomes, nanoparticles etc.).",institutionString:null,institution:{name:"Marmara University",country:{name:"Turkey"}}},{id:"61051",title:"Prof.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"100762",title:"Prof.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"St David's Medical Center",country:{name:"United States of America"}}},{id:"107416",title:"Dr.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Texas Cardiac Arrhythmia",country:{name:"United States of America"}}},{id:"64434",title:"Dr.",name:"Angkoon",middleName:null,surname:"Phinyomark",slug:"angkoon-phinyomark",fullName:"Angkoon Phinyomark",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/64434/images/2619_n.jpg",biography:"My name is Angkoon Phinyomark. I received a B.Eng. degree in Computer Engineering with First Class Honors in 2008 from Prince of Songkla University, Songkhla, Thailand, where I received a Ph.D. degree in Electrical Engineering. My research interests are primarily in the area of biomedical signal processing and classification notably EMG (electromyography signal), EOG (electrooculography signal), and EEG (electroencephalography signal), image analysis notably breast cancer analysis and optical coherence tomography, and rehabilitation engineering. I became a student member of IEEE in 2008. During October 2011-March 2012, I had worked at School of Computer Science and Electronic Engineering, University of Essex, Colchester, Essex, United Kingdom. In addition, during a B.Eng. I had been a visiting research student at Faculty of Computer Science, University of Murcia, Murcia, Spain for three months.\n\nI have published over 40 papers during 5 years in refereed journals, books, and conference proceedings in the areas of electro-physiological signals processing and classification, notably EMG and EOG signals, fractal analysis, wavelet analysis, texture analysis, feature extraction and machine learning algorithms, and assistive and rehabilitative devices. I have several computer programming language certificates, i.e. Sun Certified Programmer for the Java 2 Platform 1.4 (SCJP), Microsoft Certified Professional Developer, Web Developer (MCPD), Microsoft Certified Technology Specialist, .NET Framework 2.0 Web (MCTS). 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