User involvement is widely recognized as best practice in the development of information technology (IT) systems. In large-scale IT projects, the involvement of users and other stakeholder groups is typically in the form of representatives, as opposed to the direct (in-person) participation characteristic for smaller projects. The potential new sharing of power that representative participation entails vis-à-vis direct stakeholder involvement, and the implications of such a shift, are an important discussion in the context of participatory design. This paper extends and adds to previous work on this subject. Drawing on stakeholder interviews conducted as part of a case study of an electronic health record implementation project in Norway, this paper seeks to describe and analyze problems that can arise with representative participation in a large-scale project. Our focus is on an observed decline of interaction between health professionals participating actively in the project and their advisory units consisting of colleagues without a formal project role. The paper describes how the project’s structural arrangements might explain this decline. The paper also describes how the participating health professionals’ involvement of the advisory units at regular intervals early in the project (broad involvement) was replaced by more ad hoc and competence-oriented approaches (narrow involvement). We further use the organizational structure of democracies as the basis for two analogies, (I) participants-as-political-representatives and (II) participants-as-technocrats. The observed decline in interaction between the participating health professionals and their advisory units can be seen as a transition in role from user representative to technocrat. Generalizing from the case, we suggest that (1) a project’s structure strongly affects the possibilities of participating users to consult other users  about issues concerning the design solution, (2) a project’s structure conditions the role of participating users and who, or what, they represent, and (3) representative participation requires rethinking a project’s structure. Thus, small-scale participatory projects are to a greater extent characterized by direct participation.The involvement of users and other stakeholders is a fundamental principle in user-centered and participatory design (UCD and PD)  who are considered to act on behalf of larger stakeholder groups or organizations in matters concerning the design solution . The project documents and public description of the project, as discussed in further detail later, are ambiguous and contradictory as to the role of the SMEs—whether they are representing their regional community of practice or if they are experts providing domain knowledge to the developers?The tendency to rely on user representatives in large-scale IT projects arguably makes the role of the representative highly influential with respect to the unfolding design process and its outcome. The implications of the potential transition in power that representative participation implies vis-à-vis the direct user involvement characteristic of smaller participatory projects are an important discussion in the context of participatory design. To contribute to the ongoing discourse on the challenges of scaling up PD  in advisory units in the client health organizations that were originally established to support the SMEs’ project work. Drawing on data gathered through interviews with SMEs and their colleagues, we first investigate the central features of the above-mentioned breakdown in interaction and then the SMEs’ collegial involvement practices. Using the findings from our data analysis as a starting point for reflection, we discuss how The remainder of the article is structured as follows. We continue in Sect. Participation, as understood in PD, is a notion with strong political connotations. In comparison with, for example, UCD, where the involvement of users is primarily considered a means to ensure usable design solutions  are. Markus and Mao (user advocates) and championing its implementation in the organization , over persons who were representative of the full range of users  participation is, in many ways, controversial. PD has traditionally focused on the direct participation of users and other stakeholders as a means to understand g Schön, : the tacg Schön,  that oftg Schön,  also revAs such, direct participation has been seen as an important means to provide users genuine influence in design. Given how PD has traditionally conceptualized knowledge as inseparable from doing   initiative is another example.The project is an iterative development project with a strong focus on the involvement of various stakeholder representatives from medical specialty areas and health care services in all project phases. Despite such a focus, structural arrangements  established a joint-stock company . The main purpose of the newly formed project organization was to manage the contract and to make sure the new EHR system solution is developed according to needs and requirements of the regional health authority. This also involved ensuring that the system installations could be customized to meet the specific needs of the hospitals, municipal healthcare services, and primary care physician offices in the region.In 2012, the program responsible for the procurement of the EHR system was initiated. A US software company was contracted as the EHR system vendor in March 2019 after a tendering process. The following month, the regional health authority and the region’s largest municipality  runs and coordinates the region’s state-owned hospitals. When it comes to IT infrastructure, each individual hospital does not have the same autonomy as in other matters, as they are obliged to use the regional EHR system. Managing the transition from the current EHR systems to a single EHR system that can be used by all clinicians in the region and that supports standardized and efficient workflows is therefore the main interest of the regional public health authority.The municipality (Client organization 2) currently has its own EHR system, different from the current system in the hospitals. This EHR system exists in various configurations, which makes local installments incompatible with each other. The overall aim of the project from the perspective of the client organizations and the client group is implement a new EHR system that can allow for more coherent healthcare services for patients and health professionals in region  from the two client organizations and the client group. As previously noted, the official description of the project (in Norwegian) is ambiguous as to the role of SMEs. In some parts of the project description  decision structure to handle emerging issues related to the configuration of the new EHR solution  is in accordance with the decisions made.subject coordinators) from all client organizations. This group also makes decisions on issues of a more principal and strategic character.Level 2 of the decision structure consists of a decision group with members  consists of two members of each of the two client organizations who will make decisions on questions concerning the scope of the contracts, possible expansion of the collaboration, and other issues at top management level.The project organization has developed an implementation plan for the EHR system consisting of six phases leading up to the deployment of the final solution (“Go live”): (1) preparation phase, 2) specification phase, (3) development phase, (4) test and approval phase, (5) training phase, and (6) production setting. Figure  specificDuring the preparation phase, the project organization was established, detailed project plans were made, and a mapping of existing systems and work routines was carried out. In addition, the 400 SMEs were included in this phase. During the specification phase, the SMEs worked primarily with meeting facilitators from the project and vendor organizations and with developers from the vendor organization. The work consisted mainly of preparing workflows while aiming for a preliminary version of the EHR system. In the development phase, workflows were further developed, and the preparation of a common medical terminology commenced. For the test and approval phase, a large number of test users will take part in the testing of workflows. Integration between system modules is also part of this phase. The training phase focuses mainly on training health care personnel in the use of the new EHR system. The production phase focuses on deploying the system in the client organizations.The project is characterized by a large degree of involvement from health professionals  throughout all phases of the project. After the project organization requested the participation of SMEs as part of the project’s preparation phase, health professionals employed in the client organizations and the client group were appointed to the role either directly by their superiors or through an application process. Client organization 1  selected SMEs to cover most medical specialties in the region. Client organization 2  selected SMEs to cover the most relevant healthcare services affected by the new system. The SMEs are hired by the project organization to participate in the project on a full-time (100%) or part-time  basis. After the project, the SMEs will also likely become users of the implemented EHR system as part of their professional work.In the EHR project, the SMEs work closely with application analysts from the project organization and developers from the vendor in configuring the EHR system or adding new functionality when required. The SMEs are typically organized in groups, each managed by a leading SME (full-time position) and are responsible for the configuration of modules relevant to the medical specialty or health care service each SME represents. The SME groups are typically given weekly configuration tasks by the EHR system vendor. Most SME groups are temporary and discontinued when their assignments have been completed, while some groups are more permanent and meet over a longer period of the project’s timeline.The leading SMEs are responsible for taking issues emerging as part of the configuration work into regional consensus groups for further discussion and anchoring in the professional communities (see below). All leading SMEs are part of a common group at Level 1 in the decision-making structure.To support the SMEs and help anchor decisions related to the configuration of the new EHR system in the professional communities, the regional public health authority (client organization 1) decided to establish 12 consensus groups during the spring of 2019. The consensus groups were established as advisory units within the client organizations and were consequently not part of the project organization’s formal decision structure, described in Sect. The project management decided to let the respective leading SMEs lead the consensus group meetings. The leading SMEs were thus given a new role in the project in addition to being medical experts – in these meetings they became the “interface” between the project and the future end-users of the system Figure . The proThe establishment of the consensus groups and the leading SMEs as interfaces between the respective groups and the project further highlight the potential ambiguity associated with the leading SME role. On the one hand, the SMEs were invited to participate in the project based on their knowledge and experience in a medical specialty. On the other hand, being asked to lead the consensus group meetings also potentially gave them a representative role as the consensus groups were invented to help anchor decisions affecting the implementation of the EHR system in the client organizations. The latter suggests that the leading SMEs were not intended by the project management to be sole decision-makers in light of their medical expertise, but rather also to some extent to be representatives of a community of practice.To develop a comprehensive understanding of the issues related to representative participation in the EHR implementation project, we conducted a qualitative study consisting of semi-structured interviews with SMEs and their non-project-affiliated colleagues in the client organizations. Most of the interviewed SMEs were involved in the development of a specific EHR system module. As such, the interviewed SMEs do not represent a cross-section of SMEs involved in the project but are a rather a collection of participants collaborating on a particular part of the new EHR system. Several of the interviewed SMEs had developed professional relations with one another prior to the project.A sample of 14 respondents (R1–R14) was recruited for the study. This included five leading SMEs, two SMEs, and seven colleagues, six of whom had acted as consensus group members. The age of the respondents ranged from 28 to 67 years . Four respondents described themselves as male, while ten described themselves as female.purposive sampling and snowballing sampling . All interviews were conducted by the first author and digitally recorded. The audio recordings from the interviews were auto-transcribed using Microsoft Word 365.The transcriptions were initially coded using a stepwise-deductive inductive method Tjora, , pp. 3–8The first step in the coding process was conducted by the first author and involved listening to the audio recordings multiple times, while also looking through the auto-transcriptions in search of passages or excerpts pertaining to the topic of representative participation. Relevant excerpts in the transcripts were marked and manually checked against the audio recordings to ensure that the excerpt had been correctly transcribed before being given a code using words or phrases from the excerpt to ensure empirically close codes.The second step of the coding process involved assembling the codes into higher-order code groups labeled with a descriptive text. For each code group, the related original excerpts in the transcripts were cross-checked to verify that a suitable code group label—that is, one that reflected the wording in the empirical material—had been used. All authors took part in this step.In the third and final step, the code groups were discussed in meetings between the authors and grouped into concepts. The discussions also led to the refinement of some of the code groups. The concepts of relevance for the topic of this paper  are presented in Sect. Figure The interviews offered a rich set of data on the respondents’ perceptions of their own roles, role-related practices, and issues related to participation in the project. The results presented below, however, are limited to a particular development in the project—that is, a decline in the interaction between the leading SMEs and the consensus groups. This focus did not come as a result of an a priori intention to investigate the “breakdown” in interaction as a phenomenon. Rather, it is a consequence of our inductive coding approach to the interview data and how we, through the approach, found the declining influence of the consensus groups to be a recurring issue in the respondents’ answers to the interview questions. As specified later, the coding process also helped us become aware of both features that may explain the breakdown and how collegial involvement practices of the leading SME changed as a result.Time pressureInefficient use of colleagues’ timeCommunication and understandingThe last two concepts describe the leading SMEs’ collegial involvement practices after the breakdown:“On-demand” involvementDiscussion partnersSpecifically, the analysis helped reveal five concepts, all pertaining to the declining interaction between the leading SMEs and the consensus groups throughout the project’s first phases. The first three concepts pertain to features of this breakdown:In the following subsections, we first explain the breakdown in further detail before an elaboration of each of the five concepts noted above is provided. As part of accounting for the concepts, we present quotes from the interviews that we consider central to the respective concepts, along with our interpretations of the quotes. To make the individual quotes referable in the text, each quote is marked with a unique identifier along with a reference to the quoted respondent and their project-related role .As stated earlier, we direct particular attention in this paper toward a phenomenon pertaining to the case study, that is, the breakdown that occurred in the project regarding the interaction between the leading SMEs and the consensus groups. As the project progressed toward the specification phase, the project organization expected the leading SMEs to manage and organize meetings with the consensus groups. However, at a relatively early stage in the development phase, the interest among the leading SMEs in meeting with the consensus groups to discuss project matters appeared to be declining. The group of leading SMEs (at Level 1 in the decision-making structure) requested that the consensus group meetings no longer be considered a mandatory activity, which the subject coordinators (at Level 2 in the decision structure) approved. Because of this breakdown, the consensus groups lost their potential influence on project decisions and were replaced by other means of collegial involvement, as described later in the paper.. Initially, we had meetings with the [consensus group] maybe about two to three times every six months. That’s the group with members who are not [SMEs], but who are meant to support them [the SMEs]. We’ve had fewer meetings now, simply because there hasn’t been time—and because I’ve chosen to send questions directly to individuals in the group to avoid having to bring them up in large meetings, but instead get the concrete answer without needing to arrange a meeting where I’m supposed to deliver something... It didn’t really make sense to arrange meetings and constantly present something, when there are issues that we need prompt feedback on... In this phase [development phase], where we build content, I can’t wait two months, until the next meeting, to get an answerOne central aspect that may explain the breakdown relates to a perceived mismatch between the continuous demands of the project and the extent to which the consensus groups were able to help the leading SME fulfill their project responsibilities in a timely and efficient manner. One leading SME explained:.”). The perceived limited return of time invested in meetings with the consensus group caused the leading SME to reduce the frequency of the meetings  and also to change the form of interaction with the consensus group (as further elaborated in 5.3).This statement describes two challenges, both related to temporal aspects of the leading SME’s interaction with the consensus group. The first challenge relates to the amount of time required for preparing and facilitating meetings with the consensus group, vis-à-vis the time available for the leading SME to fulfill project-related work tasks and deadlines .time pressure the project has put on leading SMEs can be seen as a central reason for the breakdown. The gradual decline in the interaction between the leading SMEs and the consensus groups likely escalated the consensus groups’ challenges of keeping up with the pace of the project. This situation reduced the possibilities for the consensus groups to help the leading SMEs solve pressing issues in a timely manner.Based on the above, the And then we saw that what we got in return [from the consensus group] was perhaps not what we really needed—that maybe we instead needed use other forums, or e-mail, or address individuals directly—because the [consensus group] is so broadly composed that it doesn’t make sense, for example, for an assistive technology technician to sit and listen to things that don't concern him, but that I should instead arrange a meeting with the assistive technology technicians about issues that concern them, and use e-mail for minor issues for things to go quickly. Another aspect that may explain the breakdown relates to the spending of time resources in the client organization in relation to the project and, in particular, the consensus group meetings:From the perspective of the leading SME, project-related issues that require the attention of colleagues in the client organizations typically concern only individuals with specific work responsibilities or professional competencies . Rather than opting for broad involvement of colleagues in plenary discussions of issues, the leading SME considers it more efficient, potentially for all parties, to consult those that the issues concern directly (“but that I should instead arrange a meeting with the assistive technology technicians about issues that concern them”). The respondent also appears to select the forum in which to raise issues based on whom and how many the issues concern  in addition to efficiency considerations (“for things to go quickly”).A key feature of the breakdown, then, appears to be linked not only to personally perceived time pressure (cf. 5.2.1), but also to the respondent’s concern over the inefficient use of colleagues’ time the consensus group meetings represented.The need to use the [consensus group] is somewhat reduced. And because we—especially when it comes to the home service, at least—have very broad competence among the [SMEs], we don’t really have a great need for those meetings. As the following quote suggests, leading SMEs also considered it unnecessary to consult project-external resources  in cases where they perceived the required competencies to already be present internally :.”), we consider this to be a plausible interpretation of the statement.While Respondent 5 does not explicitly state that efficient use of colleagues’  time is the motivation for relying less on the consensus group The third feature of the breakdown the analysis revealed relates to challenges in the communication and understanding between the leading SMEs and the consensus groups they interacted with. One leading SME expressed the following regarding her experiences communicating with the consensus group:.”). To reduce confusion, the respondent expresses being mindful of not using project-internal terminology when communicating about the new EHR solution with non-project-affiliated colleagues, instead using more generic terms they are more likely to comprehend. The “language” barrier indicated by Respondent 3 can be regarded as impeding efficient communication and degree of understanding between leading SMEs and consensus groups.According to the respondent quoted above, project affiliates have, over time, developed an internal terminology  to describe various aspects of the EHR system being implemented. While there is a mutual understanding of the terminology within the project, allowing for efficient communication, the respondent expresses that the same terminology would not have meaning for anyone outside the project Throughout the analysis, we also became aware of other challenges related to communication and understanding between those inside and outside of the project. For example, one of the SMEs explained how he found it problematic to demonstrate project-related work in progress to colleagues who had not been involved in the development process.Respondent 1 expresses reluctance toward showing colleagues solutions that are currently being developed, due to a concern that aspects that are incomplete  may cause misunderstandings and thus lower colleagues’ acceptance of the new EHR solution. To avoid such a risk, Respondent 1 expresses a need to understand how to use the new EHR solution personally before demonstrating it to others. The interviews also revealed that other SMEs held similar attitudes.When [the leading SME] say "this,” what do they mean by "this"? We are struggling with communicating. For example, when we talk about [patient] records, we, who are not [SMEs], envision [the existing EHR system] in our minds…while [the leading SME], when she asks [a design-related question], is envisioning the entire [new EHR system]. So, there is something about defining the terms being used: what do they mean? As expressed by one consensus group member, the reluctance among several SMEs and leading SMEs toward demonstrating preliminary results made it challenging for project externals to understand, comment on, and contribute to inform the development work:Respondent 10 emphasizes that, in the lack of demonstrations of work in progress, her—and other consensus group members’—main reference point is the EHR system currently in use in the client organizations (which is to be replaced). As a consequence, consensus group members’ and the SMEs’ mental models of the new EHR system are likely to differ considerably.Based on the above, we consider the lack of both a shared terminology and concrete design artifacts from the development work to help facilitate communication and understanding between “insiders” and “outsiders” as central features of the breakdown.after the breakdown.Having described key findings related to the declining influence of the consensus groups, we now turn our attention to how the project-related collegial involvement practices of the leading SMEs continued We’ve now been told that we’re no longer required to hold those meetings, but we do so if we find it necessary…For example, when it comes to the home care service, we’ve usually contacted [the person with the right competency] directly—the one in the [consensus group] who’s among those that travel around cleaning people’s homes and who are part of a separate unit. This is something none of the SMEs are very competent in, therefore we’ve made direct contact with her. We’ve had a couple of meetings with her, needs have been explained…[and] she has given us some advice on what we should do. This way, we have used the [consensus] group. Beyond that, it has probably been a while since we’ve used anyone else [from the consensus group], and that’s because we have very competent people, with extensive professional knowledge [among the SMEs], so there hasn’t really been any need [for contacting others]. One recurring pattern in the way leading SMEs described their post-breakdown practices of collegial involvement was characterized by a more ad hoc, competence-oriented approach. The following quote gives an example:R5 describes that, after the breakdown, she and her team of SMEs have changed their practice of how consensus group members are involved in project-related issues. Instead of engaging the consensus group as a whole, as in pre-breakdown group meetings, selected members of the group are now involved whenever issues emerge  that the development team does have sufficient competencies to settle internally (“This is something none of the SMEs are very competent in.”). As such, the decision about who to involve as issues emerge is based on the consensus group members’ competence, and contact is established directly (“therefore we’ve made direct contact with her”).R5 also expresses that, given the competencies and level of relevant knowledge among the SMEs that she works with in the project, the need for involving externals has been limited . Similar opinions are also expressed in quote 3.Shifts in involvement practices—from plenary whole-group meetings held at regular intervals to “on-demand” involvement of consensus group members or other project externals—were also reported by other respondents.It is important to have a discussion partner, simply because you’re a little alone. It’s very nice to have a colleague, not having to stand alone in all the decisions that need to be made…Now, I’ve finally got a pharmacist colleague. Another central feature of the leading SMEs’ collegial involvement practices after the breakdown was the tendency to consult one or a limited set of specific, trusted colleagues  regarding emerging project-related issues. One leading SME expressed:According to the leading SME (R3), a key value associated with having a discussion partner, or a trusted colleague to discuss project-related issues with, is to avoid having to make decisions on issues single-handedly without including others. Having such a partner is regarded as a way of sharing the burden of making decisions.[she] presents to me [issues] she thinks have raised some controversy within [the project organization], or [issues] that are a bit difficult. And then we discuss back and forth, and she might get that confirmation from me—when I understand what she’s talking about—that I also agree [with her]. And that’s the way it should be. So, I don’t feel that I really contribute anything new, but maybe I can underscore the decisions she’s making and, in a way, confirm the conclusion she has reached. Describing the nature of the “partnership” between herself and the leading SME who stated the above quote, R4 gave the following account:R4 describes that the leading SME typically consults her about project-related issues that may be controversial or challenging to make appropriate decisions on. In the quote, R4 suggests that it is through the discussion with the leading SME—likely referring to possibilities for asking follow-questions and further clarification on various aspects—that she develops a sufficient basis for advising the leading SME. R4 sees her role as a discussion partner to be one of helping confirm (or reject) the leading SME’s tentative conclusions based on the information presented, rather than being someone who presents new information of relevance, or radically alternative solutions to the problem presented. From the perspective of R4, then, the discussion with the leading SME is a means for reaching important conclusions in the development of the new EHR system.We know each other very well. We have known each other since 2002, when we started studying together. So, we have a friendship in addition to a collegial relationship. In cases where discussion partnerships had been established as a collegial involvement practice, we learned that there were often relationships between the partners prior to the project. Describing her relationship with the leading SME, R4 explained:R4 does not only have a professional relationship with the leading SME she is collaborating with. The two also have a relationship on a personal level, having been friends for almost 20 years.We sit in an open landscape at work on the municipality's premises. We sit right next to each other, and we have a small closet between us, like a dresser-thing, and then it becomes like a "talk over the closet,” or we go to a small quiet room—a meeting room—and talk about it there. As part of the interviews, we also learned about the physical and social contexts under which project-related discussions between a leading SME and their partner took place:In contrast to the scheduled consensus group meetings, discussions between the leading SMEs and their trusted partner(s) typically occurred spontaneously and often as a partial result of the two parties working within close physical proximity to each other.As opposed to the “on-demand” involvement described in 5.3.1, the professional partnership between leading SMEs and selected SMEs represents a more stable relation, also characterized by more frequent interaction.Time pressure: The perceived limited return on time invested in meetings with the consensus group caused the leading SMEs to reduce the frequency of meetings. Too infrequent meetings did not provide timely answers needed by leading SMEs to fulfill project responsibilities and deadlines.Inefficient use of colleagues´ time: The leading SMEs considered the consensus group meetings to be an inefficient use of colleagues’ time, since the issues being discussed typically concerned only a small subset of the group.Communication and understanding: The lack of shared terminology and concrete design artifacts aiding the communication between “insiders” and “outsiders” of the project organization limited the exchange of information to a level that was no longer appropriate for the development project.In summary, the interviewees described the declining use of the consensus groups as being related to:“On-demand” involvement: Several leading SMEs opted for an ad hoc, competence-oriented involvement practice. This practice involved consulting relevant individual consensus group members whenever specific project-external competencies were required.Discussion partners: Another reported practice was to involve, on a longer-term basis, one, or a small group of, specific SMEs or other colleagues as consultants in project-related decisions. Typically, the discussion partner was a colleague the leading SME was well acquainted with prior to the project.Regarding post-breakdown collegial involvement, the interviewed leading SMEs described the following two emerging practices:Figure Having described central features of the breakdown as perceived by respondents, as well as involvement practices in the aftermath, an interesting question emerges: How can the features and the practices be explained as resulting from the project’s structural arrangements  The transition from one project phase to another changes the information needs of the SMEs. (2) Disproportionate representation of competencies in consensus group meetings, as the leading SMEs’ information needs become more related to particular aspects of the new EHR being developed.their perspectives and understandings of the development work taking place within the project. As meeting facilitators, the leading SMEs also had a significant impact on the meeting agenda—that is, what aspects of the project work should be given priority.Another central problem the analysis revealed was the challenges in communication and understanding between the (leading) SMEs and the consensus group members. These challenges indicate that the conceptual gap between project “insiders” and project “outsiders” was not sufficiently closed. In view of the project’s structural arrangement, this conceptual gap may potentially be seen as a consequence of the following. First, the leading SMEs acted as primary links between the project and the respective consensus groups . As facilitators of the consensus group meetings, the leading SMEs implicitly also became “filters”, as the information they offered represented Second, the pace of the project, and specifically the asynchrony between the project’s continuous information needs and the consensus group meetings, potentially further widened the conceptual gap between project insiders and outsiders. The relatively low frequency of the consensus group meetings gave the members of the consensus groups only a peripheral understanding of the development work, making it challenging to comprehend the rationale behind design proposals emerging from—and design decisions taken within—the project.Relevant structural arrangements: (1) The leading SMEs as the primary “touch-points” or links between the project and the consensus groups. (2) The pace of the project and the resulting asynchrony between the project’s continuous information needs and the consensus group meetings.While the project’s structural arrangement might help explain the declining influence of the consensus groups  experience from working within and having in-depth knowledge of the client organizations. In most cases where external competencies were required to inform a project-related decision, the leading SMEs, or the team of SMEs they interacted with, knew where to find the correct competencies within the client organizations. This in-depth knowledge of the client organization also made “on-demand” involvement practically feasible.Relevant structural arrangements: (1) The pace of the project, as given by the project timeline with its regular deliverables. (2) No strict regulations on involvement practices. (3) Stakeholder representatives with in-depth knowledge of the client organizations.The establishment of discussion partners was another collegial involvement practice that replaced the consensus group meetings. We consider the structural arrangements affording “on-demand” involvement Sect.  to also Relevant structural arrangements: Same as for “'on-demand involvement” and “communication and understanding,” in addition to sharing of physical workspace.on-demand interaction and conversation partners).In the above, we discussed various ways the structural arrangements of the EHR implementation project can be considered to have affected the SMEs’ collegial involvement practices. The transition involved moving away from relatively large and infrequent consensus group meetings with group members representing a broad set of competencies to more frequent ad hoc interactions with smaller groups or individuals . The essence of the Morgan’s political systems metaphor on organizations is the acknowledgment of conflicting interests that need to be negotiated into a mutually acceptable agreement. To facilitate further discussion, we use a political system, that is, the organizational structure of democracies, as the basis for two analogies  vote for professional politicians to represent their interests in parliament. A group of voters in a specified area who elect a representative is referred to as a constituency. It is the parliament that determines the composition of the government. Parliament also imposes control of the government and the ministries responsible for implementing government policy.Modern democracies are far more complex than the structure described above suggests, but for analogical purposes, a simplified account is sufficient. As suggested by Morgan  organizaMorgan  lists six “varieties of political rule” for his organization-as-political-system metaphor: Autocracy, Bureaucracy, Technocracy, Codetermination, Representative Democracy, and Direct Democracy. Of these, Direct Democracy corresponds to how we have described participation in early PD projects. For the current case, we have found Representative Democracy and Technocracy to be useful “varieties of political rule” for reflecting on the ambiguous role of the SMEs.SMEs as political representatives, the central structural elements of the case can be translated into elements found in the organizational structure of representative democracies, as described in Table free mandate, that is, given the authority to act as they see fit (as opposed to an imperative mandate where the holder is required to reflect the will of those they represent).In our first analogy, technocrats—technical experts , especially, those exercising managerial authority  “forced” the SMEs into a “technocrat” role, that is, acting as implementers of the project plan. Given a deliverable-oriented project plan, the SMEs’ de-prioritization of broad involvement and deliberation can be seen as a consequence, as these aspects were considered obstacles to, rather than means of, realizing the project timeline. The development of a “tribal language” among the SMEs  or indirectly (through SMEs) in the development work of one specific EHR module. As such, we do not know the extent to which the respondents’ viewpoints also represent the perspectives of SMEs participating in the development of other EHR modules in the project or their non-project affiliated colleagues. Moreover, the reported findings also need to be considered in view of the timing of the interviews. We do not know the degree to which the interviewed SMEs' perspectives and involvement practices may have changed in the aftermath of the study. Thus, the findings represent a “snapshot” in the project’s timeline.Second, as the initial coding was conducted only by the first author there is a risk of interpretation bias . However, having conducted the interviews in addition to observing several project meetings, the first author was also the author possessing most relevant contextual knowledge pertaining to the case and thus more likely to deduce plausible meanings from respondents’ statements.Third, while the results presented in Sect. Four, although we identified issues that from PD’s emancipatory perspective may question the success of the project we have studied, we need to remember that the project was never intended to follow PD principles. Hence, passing a normative “judgment” on the project is not meaningful. Instead, we consider the findings to draw attention to challenges related to large-scale participation, for which there are currently no textbook solutions to be found in PD literature, and which we hope can inspire future investigation.This paper has focused on representative participation in large-scale IT projects, using an ongoing health IT project intending to implement a common EHR system in Central Norway as a case study. In their communication to the public, the project is ambiguous as to the role of the participating health professionals (SMEs). Drawing on empirical data from the case study of an EHR implementation project, we investigated the SMEs’ collegial involvement practices and how these changed throughout the project due to various perceived challenges. This change involved a transition from attempts at broad involvement by relatively large advisory units through relatively infrequent meetings to more ad hoc, competence-based involvement of individual colleagues. Drawing on the findings, we discussed how the breakdown in the interaction and the post-breakdown involvement practices can be seen as features pertaining to the structural arrangements relative to the project.Project structure affects the level of participation: The collegial involvement practices of users involved in a project’s participatory activities are likely to be affected by the project’s structural arrangements and how it is organized. Thus, possibilities for broad involvement and deliberation are conditioned and constrained by the arrangements.Project structure affects role: A project’s structural arrangements implicitly direct who and what participants in a project represent. Structural constraints  can effectively turn user representatives into representatives of their own interests and perspectives, or “technocrats” of the project, or a mix of the above. It is therefore important that large-scale participatory projects take into consideration the role of the participating users and who, or what, they represent. Similarly, it is essential that it is made explicit for the participating users what their role entails.Representative participation requires rethinking project structure: Representative participation in large-scale IT projects, as a means to deal with the problems associated with the direct involvement of large user groups, raises issues that in many ways are comparable with those associated with representative democracy. Both require structural arrangements, that reduce the risk of representative participation becoming exclusionary. Interactions between representatives and those represented hence need to be reflected in the design of large-scale IT projects.In terms of representative participation in large-scale IT projects, the following key lessons can be drawn from the present study:We hope that the current study motivates further research on the topic of representative participation in large-scale IT projects.


Little is known about the functions and intracellular mechanisms of the endothelial cells in liver grafts. In particular, we still know little about the effect of the most recent machine perfusion techniques currently applied to improve liver transplant outcomes. In this study we analyzed different endothelial markers of both immunohistochemical and gene expression in two different biopsies (for each donor). We observed a severe depression of endothelial trophism in liver grafts, which is restored after reperfusion. This is interesting for further studies on liver grafts, especially considering that the execution of HOPE seems to improve this functional recovery. We propose that our results may help improve the knowledge on graft tissues in order to customize the perfusion techniques prior to transplant and, therefore, improve liver transplant outcomes.p < 0.001). Nestin and ERG expression was low in allocation biopsies, but increased in post-perfusion biopsies, in both immunohistochemistry and RT-PCR (p < 0.001). An inverse correlation was observed between ERG positivity and donor age. Our results indicate that LSEC trophism is severely depressed in liver grafts, but it is restored after reperfusion in standard conditions. The execution of HOPE seems to improve this recovery, confirming the effectiveness of this machine perfusion technique in restoring endothelial functions.The aim of the present study was to evaluate the homeostasis and trophism of liver sinusoidal endothelial cells (LSECs) in vivo in different stages of liver graft donation, in order to understand the effects of graft ischemia and perfusion on LSEC activity in liver grafts. Special attention was paid to grafts that underwent hypothermic oxygenated perfusion (HOPE). Forty-seven donors were prospectively enrolled, and two distinct biopsies were performed in each case: one allocation biopsy  and one post-perfusion biopsy, performed after graft implant in the recipients. In all biopsies, immunohistochemistry and RT-PCR analyses were carried out for the endothelial markers CD34, ERG, Nestin, and VEGFR-2. We observed an increase in CD34 immunoreactivity in LSEC during the whole preservation/perfusion period ( Vascular endothelial cells represent the interface between blood flow and tissue, exerting several functions beyond a mere barrier, including tissue homeostasis, metabolite and nutrient cross-transport, regulation of inflammation and neoangiogenesis, as well as control of the muscular tone of the vessel wall . Liver sIn the few last decades, the poor availability of grafts for liver transplantation has led to the search for new strategies to increase the donor pool: one of these strategies is the use of organs from extended criteria donors (ECD). The ECD inclusion criteria are age >60–65 years, and/or the presence of other criteria, such as donors in cardiovascular death (DCD), high transaminase levels or hypernatremia, long intensive care, or prolonged cold ischemia time . The macThe ETS-related gene (ERG) is a transcription factor with an emerging role in the regulation of endothelial functions, during embryogenesis, but also in several adult tissues . ERG expThe aim of the present study is to evaluate the expression of different markers of LSECs trophism and homeostasis in vivo at different stages of liver graft donation, before and after HOPE, in order to understand the effects of graft ischemia and perfusion on LSECs.The present study was approved in advance by the local Ethical Committee (code number 65/2018/SPER/AOUBo), and follows the ethical guidelines of the 1975 Declaration of Helsinki ; donors are kept anonymous. The study includes donors previously published in the context of a larger open-label, prospective, single-center, randomized clinical trial, where patients were stratified based on the contemporary presence of ECD liver criteria and randomized in a 1:1 ratio to receive a liver preserved with either HOPE after SCS during transportation or with SCS alone . Livers Allocation biopsy (A-Biopsy), performed at the stage of organ allocation for the assessment of graft suitability, as usually performed in our Institution ;Post-perfusion biopsy (PP-Biopsy), performed for the purposes of the study after graft implant in the recipients. This biopsy was specifically performed for the study.An eligibility criterion specific for the present study was the availability of two distinct biopsies:Of the 110 liver donors prospectively enrolled in the context of the monocentric clinical trial, 49 satisfied the eligibility criteria; two more donors were excluded due to the lack of sufficient tissue in A-Biopsies to perform IHC: 47 donors were therefore finally enrolled for the current study, 22 males and 25 females, with a mean age of 74.8 ± 10.1 years (range 42–87 years).Of these 47 donors, 34 (72.3%) donors were enrolled for HOPE perfusion, while 13 (27.7%) were preserved in SCS.Collected donor variables included tobacco and/or alcohol consumption, chronic use of medications; heart, lung, and liver disease; hypertension; diabetes; dyslipidemia; nephropathy; vasculopathies; dyslipidemia; and body mass index (BMI). Machine perfusion variables included flow, pressure, and resistance; gas analysis variables of the effluent perfusate included PH, pCO2, paO2, glucose, and lactate at start of perfusion, and then every 30 min.Analysis of recipients’ characteristics was not included in the present study due to the study aims and the small sample size; however, a follow-up of the recipients was preliminarily included after a mean follow-up of 305.6 ± 193.5 days (range 45–723 days). Follow-ups included early allograft dysfunction (EAD) and primary non-function (PNF) cases, post-transplant acute kidney injury (AKI) with or without the need of continuous venovenous hemofiltration (CVVH), graft survival, and recipient survival.Different endothelial markers were applied to evaluate the trophism of LSECs before and after perfusion. The term “trophism” was used to indicate the activation of those intracellular pathways leading to cell protection and/or survival in course of hypoxic stresses.A-Biopsies were routinely frozen for quick histopathological evaluation for graft suitability, and subsequently fixed in formalin and embedded in paraffin (FFPE); PP-Biopsies were directly FFPE at the stage of sampling. In all cases, FFPE tissue was routinely processed, and 2-µm-thick sections were cut for hematoxylin–eosin and reticulin silver staining, as well as for immunohistochemistry (IHC). The histopathological variables collected are the same of the donor’s checklist usually applied in our institution : portal ® ultra , following the manufacturer’s instructions. The antibodies used in the present study included: CD34 (clone QBEnd/10), Nestin (clone 10C2), and ERG (clone EPR3864). CD34 immunoreactivity was semiquantitively assessed in LSECs as mild/focal, moderate, and severe/diffuse, based on the extension of sinusoids “endothelization” from the periportal zone to the whole lobule. Nestin immunoreactivity was evaluated at two levels: (1) semiquantitively at LSEC level (when Nestin-positive sinusoids were present), applying the same method as CD34; (2) quantitatively counting the highest number of periportal Nestin-positive capillaries, which we observed to be common in our series. ERG immunoreactivity was quantitatively assessed by counting the number of ERG-positive endothelial nuclei in 10 high-power fields : the mean number of ERG-positive nuclei/10 HPF was therefore counted. As controls, two liver graft specimens from healthy living donors (age 31 and 39 years) were used: in these cases, no CD34-positive endothelization of LSEC and no significant Nestin immunoreactivity were observed (as expected); the mean number of ERG-positive nuclei was 13.3 and 14.5/10 HPF respectively.IHC was automatically performed by means of the automated immunostainer Benchmark−∆∆Ct method and data were expressed as fold changes of mRNA expression relative to A-Biopsies.Total RNA was extracted from 16 FFPE tissue samples, eight HOPE and eight SCS cases, from both A-Biopsies and PP-Biopsies, using the FFPE Recover All  according to the manufacturer’s instructions. RNA quality and concentration was evaluated by a ND-1000 spectrophotometer . Reverse transcription was performed from 0.5 μg of total RNA in 20 μL reaction volume using the High-Capacity cDNA Reverse Transcription Kit (Thermo Fisher Scientific). Real-Time PCR for the analysis of Nestin, ETS Transcription Factor (ERG) and Vascular Endothelial Growth Factor Receptor-2 (VEGFR-2) was assessed in a CFX Connect Real-Time PCR Detection System  using the SYBR green master mix (Bio-Rad Laboratories). Primer sequences were designed through the NCBI primer tool and were the following: Nestin FWD GACCCTGAAGGGCAATCACA; Nestin REV GGCCACATCATCTTCCACCA; ERG FWD TCGCATTATGGCCAGCACTA, ERG REV CGTTCCGTAGGCACACTCAA; VEGFR-2 FWD CGGTCAACAAAGTCGGGAGA; VEGFR-2 REV CAGTGCACCACAAAGACACG . Reactions were performed in triplicate and target gene expression was normalized to glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Relative quantification was assessed by the comparative 2® software for Windows, ver. 20. When applicable, t-tests, ANOVA, and non-parametric Mann–Whitney and Kruskal–Wallis tests were used to compare the variables. p values <0.05 was considered statistically significant.Variables were reported as means ± standard deviation, ranges, and frequencies. Statistical analysis was carried out using SPSSMean donors’ BMI was 26.8 ± 4.5 (range 19.9–46.7), tobacco use was recorded in 17 (36.2%) cases, history of alcohol abuse in one (2.1%) case, cardiopathies were recorded in 18 (38.3%) cases, pneumopathies in 10 (21.3%), chronic hepatopathies in two (4.3%), chronic nephropathies in four (8.5%), hypertension in 30 (63.8%), diabetes in six (12.8%) donors (one of which insulin-dependent), dyslipidemia in 16 (34.0%) cases, and arterial and venous vasculopathies in eight (17.0%) and four (8.5%) donors, respectively; 37 (78.7%) donors chronically used medications (mostly antihypertensives).Recipient follow-ups recorded seven (14.9%) cases of EAD, no cases (0%) of PNF, and 15 (31.9%) AKI cases, with seven (14.9%) cases needing CVVH. Only two recipients died in the follow-up, and only one needed retransplantation.The main histopathological characteristics of the 47 liver grafts enrolled are listed in p < 0.001, t-test; In A-Biopsies, sinusoidal CD34 expression was mild/focal in 25 (53.2%) cases, moderate in 13 (27.7%), and diffuse in nine (19.1%). In PP-Biopsies, LSEC CD34 expression was mild/focal in five (10.6%) cases, moderate in 20 (42.6%), and diffuse in 22 (46.8%). We therefore observed an increase in CD34 immunoreactivity in graft sinusoids, mean 0.7 ± 0.9 points, as confirmed by the fact that the “diffuse” cases increased from 19.1% to 46.8%. This difference was statistically significant ; however, an inverse correlation was observed between ERG positivity (on both biopsies) and donor age, as represented in p = 0.031, ANOVA test; The mean number of ERG-positive nuclei in A-Biopsy LSECs was 4.9 ± 7.5, with a maximum number ranging from 1 to 48 (mean maximum number 11.7 ± 12.5). The mean number of ERG-positive nuclei in PP-Biopsy sinusoidal endothelial cells was 22.0 ± 5.8, with a maximum number ranging from 13 to 47 (mean maximum number 28.3 ± 8.4). The increased expression of ERG was statistically significant  A-Biopsies, with a low mean number of Nestin-positive periportal capillaries . Nestin immunoreactivity in PP-Biopsy LSECs was absent in six (12.8%) cases, mild in 21 (44.6%), moderate in 14 (29.8%), and diffuse in six (12.8%). The mean number of Nestin-positive periportal capillaries was 7.4 ± 4.2 in hot spots (range 0–24). As for the first two markers, this increased Nestin expression from A-Biopsies to PP-Biopsies was statistically significant , suggesting a beneficial role of HOPE in terms of endothelial cell homeostasis and survival.RT-PCR analysis confirmed the induction of the intracellular endothelial pathways suggested by IHC: the mean fold increases between A-Biopsies and PP-Biopsies for VEGFR-2, ERG and Nestin genes were 9.95 ± 17.77, 4.63 ± 7.83, and 2.04 ± 1.83, respectively . Notablyp = 0.047, Spearman’s test). The number of Nestin-positive periportal capillaries in PP-biopsies was positively correlated with the Lactate concentration (p = 0.008), and negatively correlated with the pH (p = 0.005) at the beginning of the re-cycle. Finally, the increase in the number of ERG-positive nuclei in PP-Biopsies positively correlated with the pO2 at the end of re-cycle (p = 0.044).Among the 34 grafts who underwent to HOPE prior to liver transplantation, some perfusion characteristics correlated with the expression of the three endothelial markers. In particular, the increase in CD34 immunoreactivity in LSECs (endothelization) positively correlated with the time of the overall perfusion .The only follow-up data that showed a correlation with graft endothelial trophism was the need for CVVH after transplant, which directly correlated with CD34 positivity in PP-Biopsies, suggesting a correlation between LSEC endothelization and kidney function in liver transplant recipients. In particular, all seven CVVH cases showed strong and diffuse positivity for CD34 at PP-Biopsy  . EndMT iIn this study, we used Nestin as a more specific marker of EndMT: Nestin positivity is not normally observed in LSECs, as already reported by our group , as wellERG is a known mediator of endothelial trophism, essential for physiological and pathological neoangiogenesis , and it Another interesting finding is that this “recovery” was inversely correlated to donor age, suggesting a physiological unbalance in ERG activities with ageing. This is in line with previous observations on the progressive lack of LSEC fenestrations, in which sinusoidal dysfunction and increased hepatic microvascular resistance correlated with age ,36. The In conclusion, our results showed that LSEC trophism is severely depressed in liver grafts, but it is restored after reperfusion in standard conditions. The execution of HOPE seems to improve this recovery, confirming the effectiveness of this MP technique in restoring endothelial functions. Whether this LSEC increases functionality impacts on graft survival and transplant outcomes will be the topic of further research.


Recipients requiring ≥2 readmissions were likely to be diabetic  and have longer dialysis vintage (p = 0.01). Duration of DGF was longer with increasing number of readmissions (p < 0.001). There were no differences in patient survival for those with DGF and 0, 1 and ≥2 readmissions (p = 0.13). Graft survival, however, was lower for those with ≥2 readmissions (p < 0.0001). This remained true when accounting for death-censored graft loss (p = 0.0012). Additional subgroup analysis was performed on mate kidneys with and without DGF and mate kidneys, both with DGF, with and without readmissions. For these subgroups, there were no differences in patient or graft survival. As a whole, patients with DGF have excellent outcomes, however, patients with DGF requiring ≥2 readmissions have lower graft survival. A better understanding of recipient variables contributing to multiple readmissions may allow for improvements in the utilization of DGF at-risk kidneys.Concerns regarding outcomes and early resource utilization are potential deterrents to broader use of kidneys at risk for delayed graft function (DGF). We assessed outcomes specific to kidneys with DGF that required early readmission following transplant. Three groups were identified: 1) recipients with DGF not requiring readmission, 2) recipients with DGF having an isolated readmission, and 3) recipients with DGF requiring ≥2 readmissions. Most recipients either required a single readmission (26.8%,   Delayed graft function (DGF) is a common post-transplant event. Although the incidence varies between transplant centers, it is known to occur at a higher rate with certain types of kidney allografts, such as those coming from high kidney donor profile index (KDPI) donors, acute kidney injury (AKI) donors and donation after circulatory death (DCD) donors -3. The cn = 12) and with primary nonfunction (n = 7) were excluded as were recipients of deceased donor kidneys without DGF (n = 616) (This is a retrospective review of patients with DGF who received deceased donor kidney transplants at Mayo Clinic Arizona from 2015 through 2020. Recipients with DGF were assessed based on their need for readmission. Three groups were identified: 1) recipients with DGF not requiring readmission, 2) recipients with DGF having a single isolated readmission, and 3) recipients with DGF requiring ≥2 readmissions. Living donor kidney transplants and multivisceral transplants were not included in this analysis. Recipients with early (<7 days post-transplant) technically related graft losses (n = 616) . The stuDGF was defined as the need for dialysis within 7 days of kidney transplant. Acute kidney injury (AKI) donors were defined as those with Acute Kidney Injury Network (AKIN) stage 2-3  -3.Data on readmissions was obtained using the electronic health record. The electronic health record was queried for the date of admission, date of transplant procedure, date of discharge and initial length of stay. Early readmission following kidney transplant was defined as occurring within 60 days of the index procedure. A readmission was defined as any hospital stay ≥24 h. The International Classification of Diseases (ICD) 10 codes (ICD 9 prior to October 2015) for the primary readmission discharge diagnosis were recorded. Readmissions related to early renal recovery include those attributed to volume status (overload or dehydration) and electrolyte management. Percentages of missing variables are noted in Protocolized induction and maintenance immunosuppression was used for all kidney transplant recipients. Basiliximab induction was used for patients over 65 years of age; patients less than 65 years of age received depleting induction. Those who received basiliximab were continued on maintenance corticosteroids while steroid discontinuation occurred by post-transplant day five for those receiving depleting induction. Tacrolimus and mycophenolate mofetil were used for maintenance immunosuppression. Tacrolimus was started on post-transplant day 1-2 irrespective of DGF. Tacrolimus trough levels were maintained between 8–10 ng/ml for the first month post-transplant and between 6–8 ng/ml after 1 month. All reported rejections were biopsy-proven. Early acute cellular rejection (ACR) was defined as occurring within 6 months of transplant. Estimated GFR (eGFR) was calculated using the CKD-EPI formula. Six-minute walk distance was used to assess candidate suitability for transplant as previously described .Recipients are typically discharged between post-transplant days 2 and 3 regardless of DGF . For thoPrimary outcomes were post-transplant hospital length of stay, early ACR, eGFR, and patient and allograft survival comparing recipients with DGF having 0, 1 and ≥2 post-transplant readmissions. Secondary outcomes were obtained through subgroup analyses on mate kidneys. Two subgroup analyses were completed: 1) mate kidney with and without DGF, and 2) mate kidneys both with DGF but with and without hospital readmissions. Primary outcomes were applied to the subgroup analyses.p-value of less than 0.05 was considered statistically significant. Descriptive statistics were reported as mean ± standard deviation, mean ± standard deviation and median, or median and interquartile range (IQR); categorical variables were reported as count and percent. Data was analyzed using GraphPad Prism 9.3.1  and BlueSky (Version 7.40).Chi-square analysis was used for categorical variables and t-tests were used for quantitative variables. Graft and patient survival were calculated by Kaplan-Meier survival analysis. We also used a Cox proportional hazard model to adjust for baseline differences in death-censored graft survival. A n = 922) had DGF. Of these 922 kidneys with DGF, 13.3% were high KDPI (n = 123), 29.7% (n = 275) were from DCD donors, and 48.4% (n = 446) were from AKI donors. Characteristics of recipients with DGF requiring 0, 1 and ≥2 readmissions are shown in n = 247) or no readmission ; 17.1% (n = 158), had ≥2 readmissions. In general, recipients were similar in age (p = 0.11) and race (p = 0.65). Recipients for all groups were more likely to be male (p = 0.56) and be on dialysis at the time of transplant (p = 0.16). Recipients requiring ≥2 readmissions were more likely to be diabetic  and have longer dialysis vintage . There were no differences observed between the three groups with regard to pre-transplant ejection fraction (p = 0.68), 6-minute walk distance (p = 0.07) and need for midodrine (p = 0.18).In total, there were 1557 kidney transplants during this time period. Of those, 59.2% (p = 0.46) and more likely to be male (p = 0.21). The median KDPI score was 52.0% (p = 0.13); high KPDI (KDPI ≥85%) kidneys were equally distributed between the three groups . A similar distribution of AKI  and DCD  kidneys allografts was observed between the groups. Distribution of locally, regionally, and nationally allocated kidneys (p = 0.15) and cold ischemia time  were also similar and did not vary between the three groups. Alemtuzumab was the most commonly used induction agent for all groups (p = 0.62).Donor characteristics for the three groups are shown in p < 0.001). Readmissions occurred later post-transplant for those recipients with one readmission compared to those with ≥2 readmissions . Recipients with one readmission were also more likely to have had resolution of DGF prior to readmission compared to those with ≥2 readmissions (median 6 vs. 1 day(s), p < 0.001). Despite differences in duration of DGF, there were no differences in initial hospital length of stay (LOS)  or early ACR events (p = 0.31). At 4 months post-transplant, there were no differences between the groups with regard to overall eGFR (p = 0.26), although the percentage of individuals with an eGFR <30 ml/min was higher for those requiring ≥2 readmissions . At 1- and 2-years post-transplant, there were no differences in overall eGFR  or eGFR <30 ml/min .Post-operative outcomes for recipients with DGF requiring 0, 1 and ≥2 readmissions are shown in p = 0.13). Graft survival, however, was lower for those with ≥2 readmissions (p = 0.0012). This remained true when accounting for death-censored graft loss (p < 0.0001)  . At 1 ye 0.0001) .In assessing the initial index readmission for those with 1 and ≥2 readmissions, infection, early renal recovery related factors, and surgical complications were the most common indications observed . Subsequp = 0.01) and less likely to be preemptive . Other characteristics such as age (p = 0.11), race (p = 0.23), presence of diabetes (p = 0.08), and dialysis vintage (p = 0.94) were similar between the two groups.Of the 922 kidney transplants with DGF, 111 had mate kidneys without DGF. Patient characteristics for mate kidneys with and without DGF are shown in p = 0.27). There were no differences in CIT (p = 0.48).Median donor age was 37 years and 62.2% of donors were male . The medp = 0.002) and the median duration of DGF was 11.0 days. Readmissions were more common for mate kidneys with DGF . Although the overall number of readmissions per recipient did not vary between those with and without DGF , mate kidneys mate kidneys with DGF were more likely to have >2 readmissions . Early ACR events were uncommon and did not vary between the two groups . There were no differences in overall eGFR at 4-months (p = 0.80), 1-year (p = 0.94) and 2-year (p = 0.69) although eGFR <30 ml/min was more commonly observed in mate kidneys with DGF at 4 months  and 2 years .Post-operative outcomes are shown in p = 0.91) or graft survival  (p = 0.56).In comparing mate kidneys with and without DGF, there were no differences in patient  . This rep = 0.26), body mass index (BMI) (p = 0.89), and presence of diabetes (p = 0.29). Recipients requiring readmission were more likely to be male . A similar distribution of preemptive recipients was noted in both groups . There were no differences in dialysis vintage (p = 0.53).Of the 922 kidney transplants with DGF, there were 89 mate kidneys with and without readmission. Recipient characteristics of DGF mate kidneys with and without readmission are shown in p = 0.27). CIT was similar for both groups (p = 0.88).The median donor age was 38 years and 64.1% of donors were male . Median p = 0.98), hospital length of stay (p = 0.96) and early ACR events (p > 0.99). There likewise were no differences in patient  or graft survival  (Post-Transplant outcomes from DGF mate kidneys with and without readmission are shown in  = 0.91) .Concerns related to outcomes, along with increased need for early resource utilization, such as dialysis and hospital readmissions, are believed to be deterrents to the broader use of kidneys at risk for DGF -8. AlthoIn this study, 59.2% of recipients experienced DGF following transplant. Despite 13.3% of recipients receiving high KDPI kidneys, 29.7% receiving DCD kidneys and 48.4% receiving AKI kidneys, the overall median hospital length of stay was 3 days and the majority of recipients either did not have any readmissions (56.1%) or had an isolated single admission (26.8%). These findings are consistent with our center’s experience in using DGF at-risk allografts (DGF continues to be viewed as an adverse event within the transplant community. This negative connotation associated with DGF is largely driven by studies suggesting a correlation between hospital readmissions, increased resource utilization and other inferior outcomes possibly as a result of surgical complications, infection and rejection -5,14-15.Competing variables contribute to transplant outcomes ,19. As sTo our knowledge, this is the first study assessing both variables and outcomes specific to DGF kidneys as well as differences in readmission outcomes. It is, however, important to note that, as a single center study, there are limitations as a result of biases introduced through center-specific protocolized practices. As a center with experience in DGF at-risk kidney allograft utilization, the outcomes described here are reflective of carefully selected organs. Donor-recipient pairing remains a crucial component influencing outcomes. Nonetheless, we feel that this data is meaningful. DGF is common event that continues to be associated with a negative connotation throughout the transplant community. More broadly, this association has been linked to kidney allografts that have good outcomes, such as those from DCD and AKI donors, and continues to be a deterrent to broader utilization. As such, we hope to improve utilization of these discard at-risk organs by sharing our experience.DGF is a common occurrence in high KDPI, DCD and AKI kidneys. Patients with DGF have excellent outcomes as a whole, however, patients with DGF requiring ≥2 readmissions have lower graft survival compared to those with DGF and 0 or 1 readmissions. Independent of DGF, the presence and severity of recipient comorbidities affect transplant outcomes. A better understanding of recipient variables contributing to multiple readmissions may allow for better utilization of DGF at-risk kidneys.


Antimicrobial-resistant Acinetobacter species are implicated in a variety of infections including nosocomial bacteraemia, secondary meningitis and urinary tract infections. Carbapenem including meropenem-resistant Acinetobacter is recognized as one of the most difficult antimicrobial-resistant gram-negative bacilli to control and treat. It was classified as an urgent threat by Centers for Disease Control and Prevention in 2019 Antibiotic Resistance Threats Report. This study was carried out to determine the prevalence of meropenem resistance among acinetobacter positive clinical samples in a tertiary care centre.A descriptive cross-sectional study was carried out in microbiology department of Clinical Laboratory Services among Acinetobacter positive clinical samples of a tertiary care center in Nepal. The culture and sensitivity reports of various clinical samples from April 2018 to April 2020 which were positive for Acinetobacter species were taken from hospital records section. Convenience sampling was done. Meropenem-resistant Acinetobacter samples were studied. Ethical approval was received from Institutional Review Committee (Ref No. 076/77/40). Analysis of data was done using Statistical Package for the Social Sciences version 26. Point estimate at 95% Confidence Interval calculated with ferquency.Out of 121 Acinetobacter isolates, prevalence of meropenem-resistant Acinetobacter was reported in 93 (76.9%) at 95% Confidence Interval (69.39-84.40). Among the meropenem-resistant Acinetobacter samples, most of the samples were collected from the sputum 70 (75.2%) followed by blood 8 (8.6%).High prevalence of meropenem-resistant Acinetobacter species in our hospital setting is alarming. In addition, there is emergence of resistance against even the last resort drugs which is creating a treatment crisis. There has been emergence of additional acquired resistance over last three decades.3Acinetobacter species are aerobic Gram-negative, catalase-positive, oxidase-negative coccobacilli.5 Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) program that earlier revealed meropenem and imipenem as the most active agents against Acinetobacter baumannii over the years reported their marked increase in resistance rates.7 The emerging resistance has led to treatment failures and prolonged hospitalization.9Carbapenems  have been considered as highly potent agents in the treatment of serious Acinetobacter infections.10 This study was carried out to determine the prevalence of meropenem resistance among acinetobacter positive clinical samples in a tertiary care centre.Centers for Diseases control and Prevention (CDC) has classified Carbapenem-resistant Acinetobacter as an urgent threat in 2019 Antibiotic Resistance Threats Report.A descriptive cross-sectional study was carried out in the microbiology department of Clinical Laboratory Services (CLS) of KIST Medical College and Teaching Hospital (KISTMCTH), Lalitpur, which is a tertiary care center in Nepal. The culture and sensitivity reports of various clinical samples that were positive for Acinetobacter species between April 2018 and April 2020 were taken from the hospital records section. Ethical approval was received from Institutional Review Committee (Ref No. 076/77/40). Clinical samples  from which Acinetobacter species were isolated were included in this study. Also, the specimens growing more than one bacterial isolates along with Acinetobacter species were included. Acinetobacter samples that were resistant to meropenem were identified and analyzed. Those samples from which Acinetobacter species were not isolated and whose records did not reveal complete data were excluded.Convenience sampling was done and the sample size (n) was calculated as,2 × p × q / e2n = Z2 × 0.5 × (1 - 0.5) / (0.09)2  = (1.96)  = 119Where,n = required sample sizeZ = 1.96 at 95% Confidence Interval (CI)p = prevalence for maximum sample size, 50%q = 1-pe = margin of error, 9%Our calculated sample size was 119 but our collected sample was 121.11 Antibiotics included were Amikacin (30μg), Gentamicin (10μg), Trimethoprimsulfamethoxazole (1.25/23.75μg), Ceftriaxone (30μg), Ceftazidime (30μg), Ciprofloxacin (5μg), Piperacillin (30μg), Piperacillin/Tazobactam (100/10μg), meropenem (10μg), Imipenem (10μg),Tigecycline (15μg), Colistin (10μg) and Polymyxin B (300units) (Hi-Media India Pvt. Ltd). Findings were classified as sensitive, intermediate, and resistance.11The antimicrobial susceptibility of all isolates was determined by the standard Kirby Bauer disk diffusion method according to norms of the Clinical Laboratory Standards Institute (CSLI).11 Drug-resistant (DR) is non-susceptibility to one or more antibiotics which can be multidrug-resistant (MDR), extensively drug-resistant (XDR) or pandrug-resistant (PDR). MDR is defined as non-susceptibility to at least one agent in three or more antimicrobial categories. XDR is defined as non-susceptibility to at least one agent in all but two or fewer antimicrobial categories . PDR is defined as non-susceptibility to all agents in all antimicrobial categories (i.e. no agents tested as susceptible for that organism).12A bacterial isolate was considered non-susceptible to an antimicrobial agent when it tested resistant, intermediate or non-susceptible when using clinical breakpoints as interpretive criteria.Data was entered and analysis was carried out through Statistical Package for the Social Sciences (SPSS) version 26. Descriptive analysis of all the data was done and point estimate at 95% Confidence Interval was calculated along with frequency and proportion for binary data.Report of various clinical samples from April 2018 to April 2020, were analyzed. There were 204 Acinetobacter isolated. Culture and sensitivity for meropenem was tested in 121 samples, prevalence of meropenem resistance was 93 (76.9%) .Meropenem-resistant Acinetobacter was isolated slightly higher from males than females. Elderly patients of age above 45 were affected the most .Among the meropenem-resistant Acinetobacter samples, most of the samples were collected from the sputum 70 (75.2%) followed by blood 8 (8.6%) .Antimicrobial susceptibility of Acinetobacter positive clinical samples was tested for Amikacin, Ceftriaxone and other antibiotics which showed high resistancee along with meropenem .Meropenem resistant Acinetobacter were resistant to most of the first line antibiotics with 93 (100%) resistance towards cefotaxime, ampicillin and ceftriaxone .They were mostly sensistive towards tigecycline, polymixin B and colistin. All meropenem-resistant isolates were multidrug-resistant, 77 (82.8%) isolates were extensively drug-resistant that was excluding one pandrug-resistant. Pandrug-resistant Acinetobacter isolate was reported from a sputum sample of a 78-year-old male.Co-infection of Acinetobacter with other gram negative bacteria was observed in 14 cultures, Klebsiella was commonest among associates 11 (78.6 %) followed by Pesudomonas 2 (14.3 %) and Escherichia coli 1 (7.1%).2 It is intrinsically resistant to a broad range of antibiotics. However, there has been an emergence of additional acquired resistance over last three decades.3 Carbapenems  have been considered as extremely potent agents in the treatment of serious infections caused by Acinetobacter.5 There has been an increasing rise in carbapenem-resistant Acinetobacter baumannii (CRAB) one of the genetic factors being mainly the acquisition of carbapenem-hydrolysing oxacillinase genes.3Acinetobacter species are implicated in causing pneumonia, bacteraemia, urinary tract infections, meningitis and wound infections.10 It is recognized as one of the most difficult antimicrobial-resistant gram-negative bacilli to control and treat. Reports reveal that the rapid increase in the prevalence of CRAB across the world has led to treatment failures and prolonged hospitalization.9 In 2017 the World Health Organization included CRAB in the global priority list of antibiotic-resistant bacteria as first priority  to guide discovery, research and development of new drugs.13Carbapenem-resistant Acinetobacter was classified as an urgent threat in 2019 Antibiotic Resistance Threats Report by CDC.6 It reported meropenem and imipenem as the most active agents against Acinetobacter baumannii, with resistance rates of 18% and 16%, respectively. However, the resistance rate was markedly increased to 43.4% for meropenem and 42.5% for imipenem as revealed by the subsequent data from 40 centers in 12 countries participating in the MYSTIC program (2006).7Many studies have been carried out since decades to determine the emergence of carbapenem including meropenem-resistant Acinetobacter species. Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) program studied the antimicrobial susceptibility of 490 Acinetobacter baumannii strains collected from 37 centers in 11 European countries from 1997 to 2000.15 However, higher prevalence was reported by Parajuli, et al. and Yadav, et al. where meropenem resistance was 84.4% and 89.4% respectively.17In developing countries like Nepal too, resistance towards carbapenem, is increasing. In our study, prevalence of meropenem resistant Acinetobacter was observed in 93/121 (76.9%) samples which is very high compared to study done by Baral, et al. and Mishra, et al. where it was 28.5% and 50% respectively.18 Highest number of infections were among patients of age group above 45 years which was similar to study done by Yadav, et.al. which also showed this bacteria to have a higher predilection for elderly patients.17More than half of meropenem-resistant Acinetobacter species along with Acinetobacter positive isolates were from respiratory specimen which was consistent with the finding that Acinetobacter are usually associated with lower respiratory tract infections.19 SENTRY study reported that Gram negative bacterial resistance to imipenem changed from 34.5% in 2006 to 59.8% in 2009 across the world.20In our study resistance towards imipenem was 73.4% which was greater than twice reported by Raut, et al. in western Nepal.21The increasing carbapenem-resistant Acinetobacter spp. has narrowed the treatment options with a combination of reserved drugs such as colistin, polymyxin B, and tigecycline being the only remaining choice to treat these cases.22 However, in our study 2.3% of the total Acinetobacter isolates were resistant to each colistin and polymyxin-B and 3.8% were resistant to tigecycline. Meropenem resistant Acinetobacter were 100% resistant towards cefotaxime, ampicillin and ceftriaxone. All meropenem resistant Acinetobacter were multidrug-resistant, 77 (82.8%) isolates were extensively drug-resistant that was excluding one pandrug-resistant. There have been reports from across the world where resistance to colistin was highest in Asia followed by Europe. Reports from Bulgaria and Spain showed resistance rates 16.7% and 19.1%, respectively.23In multiple tertiary care centers in Nepal, Acinetobacter strains were reported to be 100% sensitive to colistin, polymixin B and tigecycline.24Our study reported 6.9% Acinetobacter positive samples had co-infection with other gram negative bacteria, Klebsiella being the commonest (5.3%). These co-infections suggests the importance of choosing the appropriate antimicrobial therapy since it may increase patient mortality.25 However, in our center, Kirby-Bauer Disc Diffusion Method is used. Also, this study was carried out in one tertiary care center. Hence, with the available data, only limited picture of resistant Acinetobacter species could be viewed.This study has few limitations. To determine colistin susceptibility, it is recommended by International standard-setting organizations such as the Clinical and Laboratory Standards Institute (CLSI) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) joint polymyxin working group, March 2006, to use broth microdilution method, in which cation adjusted Mueller-Hinton broth is used.Prevalence of meropenem-resistant Acinetobacter species in our hospital settings is high and it is highly concerning. This has left reserve drugs like Colistin, Polymyxin B and Tigecycline as the only option available. However, there is development of resistance against these agents as well which signifies that there is an emerging treatment crisis to fight against drug-resistant Acinetobacter species. This can be minimized to some extent if antibiotics especially those with broad-spectrum activity and those identified as drugs of last resort, are used judiciously. Along with formulation of antimicrobial policies, solutions beyond the paradigm of antimicrobials should also be sought to address this problem.