Communication and Contextual Factors in Robotic-Assisted Surgical Teams: Protocol for Developing a Taxonomy.

BACKGROUND: Robotic-assisted surgery (RAS) has been rapidly integrated into surgical practice in the past few decades. The setup in the operating theater for RAS differs from that for open or laparoscopic surgery such that the operating surgeon sits at a console separate from the rest of the surgical team and the patient. Communication and team dynamics are altered due to this physical separation and visual barriers imposed by the robotic equipment. However, the factors that might comprise effective communication among members of RAS teams and the contextual factors that facilitate or inhibit effective communication in RAS remain unknown. OBJECTIVE: We aim to develop a taxonomy of communication behaviors and contextual factors that influence communication in RAS teams. We also aim to examine the patterns of communication behaviors based on gender. METHODS: We will first perform a scoping review on communication in RAS to develop a preliminary taxonomy of communication based on the existing literature. We will then conduct semistructured interviews with RAS team members, including the surgeon, assisting surgeon or trainee, bedside or first assistant, nurses, and anesthetists. Participants will represent different disciplines, including urology, general surgery, and gynecology, and have a range of experiences in RAS. We will use a reflexive thematic analysis to analyze the data and further refine the taxonomy. We will also observe live robotic surgeries at Royal College of Surgeons in Ireland (RCSI)-affiliated hospitals. We will observe varying lengths and conditions of RAS procedures to a capture a wide range of communication behaviors and contextual factors to help finalize the taxonomy. Although we anticipate conducting 30 interviews and 30 observations, we will collect data until we achieve data sufficiency. We will conduct data collection in parallel with data analysis such that if we identify a new behavior in an interview, we will follow up with questions related to that behavior in additional interviews and/or observations. RESULTS: The taxonomy from this project will include a list of actionable communication behaviors, contextual factors, their descriptions, and examples. As of May 2024, this project has been approved by the RCSI Research and Ethics Committee. Data collection started in June 2024 and will continue throughout the year. We plan to publish the findings as meaningful results emerge in our data analysis in 2024 and 2025. CONCLUSIONS: The results from this project will be used to observe and train surgical teams in a simulated environment to effectively communicate with each other and prevent communication breakdowns. The developed taxonomy will also add to the knowledge base on the role of gender in communication in RAS and produce recommendations that can be incorporated into training. Overall, this project will contribute to the improvement of communication skills of surgical teams and the quality and safety of patient care. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/54910.

Remote feedback in endovascular simulation training: a mixed-methods study.

BACKGROUND: There is an increasing need to increase simulation-based learning opportunities for vascular surgery residents in endovascular skills training. This study aims to explore the effectiveness of remote expert instructional feedback of endovascular simulation-based education, as a means of increasing training opportunities in this area for vascular surgery residents. METHODS: A mixed-methods study design was adopted. Twelve vascular surgery residents from Ireland were tasked with completing two endovascular renal artery procedures: one with in-person expert feedback and the other with remote instruction. Participants ranged in experience levels from second year to final year of residency. Following the training activities, interviews and a questionnaire were employed to gather information on the usefulness of remote feedback. RESULTS: There was no significant difference reported by participants using a post-event validated questionnaire between remote and in-person feedback. During the interviews, participants expressed mixed feelings about the presence of the educator while practicing, but they eventually saw no limiting factors to their practice when the trainer provided remote feedback. When receiving performance feedback remotely, clear communication and a shared knowledge of the task development are critical to success. CONCLUSIONS: We believe these findings can inform the design and development of remote learning and assessment of endovascular skills training and ultimately provide increased opportunities for more skills practice for vascular surgical residents.

Design and utilisation of a novel, high-fidelity, low-cost, hybrid-tissue simulation model to facilitate training in robot-assisted partial nephrectomy.

Robot-assisted partial nephrectomy (RAPN) has rapidly evolved as the standard of care for appropriately selected renal tumours, offering key patient benefits over radical nephrectomy or open surgical approaches. Accordingly, RAPN is a key competency that urology trainees wishing to treat kidney cancer must master. Training in robotic surgery is subject to numerous challenges, and simulation has been established as valuable step in the robotic learning curve. However, simulation models are often both expensive and suboptimal in fidelity. This means that the number of practice repetitions for a trainee may limited by cost restraints, and that trainees may struggle to reconcile the skills obtained in the simulation laboratory with real-world practice in the operating room. We have developed a high-fidelity, low-cost, customizable model for RAPN simulation based on porcine tissue. The model has been utilised in teaching courses at our institution, confirming both feasibility of use and high user acceptability. We share the design of our model in this proof-of-concept report.

A comparative analysis of student, educator, and simulated parent ratings of video-recorded medical student consultations in pediatrics.

BACKGROUND: Simulation-based education (SBE) affords learners opportunities to develop communication skills, including those related to pediatrics. Feedback is an integral part of SBE, and while much research into feedback from multiple sources exists, the findings are mixed. The aim of this comparative study was to replicate some of this work in a novel area, pediatric medical education, to better understand how multisource feedback (self, educator, and simulated parent) may inform learning and curriculum design. METHODS: During their pediatric rotation, medical students participated in a consultation with a simulated parent, engaged in video-assisted self-reflection, and received feedback from both an educator and the simulated parent through an e-learning platform. The Pediatric Consultation Skills Assessment Tool (PCAT) was used for self-assessment and educator feedback, and the Consultation and Relational Empathy (CARE) measure was used for simulated parent feedback. RESULTS: Our results showed that high-performing students underrated their performance, and low-performing students overrated their performance. Feedback from multiple sources helps to identify both areas of weakness in student performance and areas of weakness in student self-appraisal. Overall, general areas of weakness identified for the learners related to making contingency plans and providing easy-to-understand explanations for simulated parents. Some simulated parent feedback did not align with educator and student ratings, highlighting the value of including the simulated parent perspective. Our findings question whether a third party can reliably judge the simulated parent's level of understanding. CONCLUSION: Multisource feedback allows students to develop layered insights into their performance and supports self-appraisal. Aggregating feedback through an e-learning platform allows educators to gain greater insights into the strengths and weakness of students and design a more tailored teaching plan to support student needs.

Collating evidence to support the validation of a simulated laparotomy incision and closure-training model.

BACKGROUND: It is essential to evaluate the functionality of surgical simulation models, in order to determine whether they perform as intended. In this study, we assessed the use of a simulated laparotomy incision and closure-training model by collating validity evidence to determine its utility as well as pre and post-test interval data. METHOD: This was a quantitative study design, informed by Messick's unified validity framework. In total, 93 participants (surgical trainees â€‹= â€‹80, experts â€‹= â€‹13) participated in this study. Evaluation of content validity and the models' relationships with other variables was conducted, along with a pre and post-test confidence assessment. RESULTS: The model was deemed realistic and useful as a teaching tool, providing strong content validity evidence. In assessment of relationships with other variables, the expert group out-performed the novice group conclusively. Pre and post-test evaluation reported a statistically significant increase in confidence levels. CONCLUSION: We present strong validity evidence of a novel laparotomy incision and closure simulation-training model.

'They mirror what they see': A constructivist grounded theory study of simulation culture in four professional domains in Ireland.

PURPOSE: In simulation-based education (SBE), educators integrate their professional experiences to prepare learners for real world practice and may embed unproductive stereotypical biases. Although learning culture influences educational practices, the interactions between professional culture and SBE remain less clear. This study explores how professional learning culture informs simulation practices in healthcare, law, teacher training and paramedicine. METHODS: Using constructivist grounded theory, we interviewed 19 educators about their experiences in designing and delivering simulation-based communication training. Data collection and analysis occurred iteratively via constant comparison, memo-writing and reflexive analytical discussions to identify themes and explore their relationships. RESULTS: Varied conceptualizations and enactments of SBE contributed to distinct professional learning cultures. We identified a unique 'simulation culture' in each profession, which reflected a hyper-real representation of professional practice shaped by three interrelated elements: purpose and rationale for SBE, professional values and beliefs, and educational customs and techniques. Dynamic simulation cultures created tensions that may help or hinder learning for later interprofessional practice. CONCLUSION: The concept of simulation culture enhances our understanding of SBE. Simulation educators must be mindful of their uni-professional learning culture and its impacts. Sharing knowledge about simulation practices across professional boundaries may enhance interprofessional education and learners' professional practice.

Developing a clamshell thoracotomy training model to support hybrid teaching in simulation-based education.

OBJECTIVE: Thoracotomy is an acute, time-sensitive procedure. Simulation-based education provides a safe-learning platform to learn these techniques under close supervision. METHODS: We used the spiral model and concepts of functional fidelity to guide the evolutionary design and fabrication of a hybrid thoracotomy simulator. RESULTS: This model simulates a clamshell thoracotomy that physically integrates with bespoke manikins and adds a high-fidelity technical skills element to immersive team-based simulation training. CONCLUSIONS: We describe the creation of a thoracotomy simulation model that allows trainees to practice these techniques in a safe-learning environment.

Mapping the Terrain of Faculty Development for Simulation: A Scoping Review.

ABSTRACT: Understanding what interventions and approaches are currently being used to improve the knowledge, skills, and effectiveness of instructors in simulation-based education is an integral step for carving out the future of simulation. The current study is a scoping review on the topic, to uncover what is known about faculty development for simulation-based education.We screened 3259 abstracts and included 35 studies in this scoping review. Our findings reveal a clear image that the landscape of faculty development in simulation is widely diverse, revealing an array of foundations, terrains, and peaks even within the same zone of focus. As the field of faculty development in simulation continues to mature, we would hope that greater continuity and cohesiveness across the literature would continue to grow as well. Recommendations provided here may help provide the pathway toward that aim.

Training simulated participants for role portrayal and feedback practices in communication skills training: A BEME scoping review: BEME Guide No. 86.

BACKGROUND: Providing feedback is a key aspect of simulated participants' (SPs) educational work. In teaching contexts, the ability to provide feedback to learners is central to their role. Suboptimal feedback practices may deny learners the valuable feedback they need to learn and improve. This scoping review systematically maps the evidence related to SPs' role as educators and identifies how SPs prepare for their role and feedback practices. METHODS: The authors conducted a scoping review and included a group of international stakeholders with experience and expertise in SP methodology. Five online databases were systematically searched and ERIC, MedEdPortal and MedEdPublish were hand searched to identify relevant studies. Inclusion/exclusion criteria were developed. Data screening and subsequently data charting were performed in pairs. The results of data charting were thematically analysed including categories relating to the Association of SP Educators (ASPE) Standards of Best Practice (SOBP). RESULTS: From 8179 articles identified for the title and abstract screening, 98 studies were included. Studies reported the benefit of SPs' authentic role portrayal and feedback interactions for learners and on the reported learning outcomes. Data was heterogeneous with a notable lack of consistency in the detail regarding the scenario formats for communication skills training interventions, SP characteristics, and approaches to training for feedback and role portrayal. CONCLUSIONS: The published literature has considerable heterogeneity in reporting how SPs are prepared for role portrayal and feedback interactions. Additionally, our work has identified gaps in the implementation of the ASPE SOBP, which promotes effective SP-learner feedback interactions. Further research is required to identify effective applications of SP methodology to prepare SPs for their role as educators.

Gender Equality Training for Students in Higher Education: Protocol for a Scoping Review.

BACKGROUND: The principles of gender equality are integral to the goals, targets, and indicators of all sustainable development goals. Higher education institutes can be powerful agents for promoting gender equality, diversity, and inclusion not only in the higher education context but also in society as a whole. To address and overcome gender inequality in the higher education environment, experts posit that change needs to occur from day 1 of the student's academic experience. To this end, training is required. A preliminary review of the literature indicates that multiple gender equality-based training programs or initiatives for students have been designed and evaluated in second and third-level education settings. Examples of educational activities undertaken include delivery of didactic teaching, participation in a face-to-face collaboration project, site visits, case studies, and coaching. Yet, our initial search indicated that, to date, a comprehensive review collating the available evidence on gender equality training for third-level students has not yet been carried out. OBJECTIVE: Our review seeks to identify and explore the existing literature on gender equality training interventions for third-level students, with a particular emphasis on training content, methodology, and outcome evaluation. METHODS: This scoping review will be structured using the Arskey and O'Malley's 5-stage framework and will consider empirical research and other relevant published works that address gender equality training. Systematic searches will be carried out in 6 research databases and the gray literature using key search terms. Inclusion and exclusion criteria have been defined, and a data charting tool created to methodically extract information from selected literature. The free web software Rayyan will be used for primary screening where each reference will be screened in duplicate first by title, then abstract, and finally by full text. RESULTS: This review forms part of the LIBRA (Balance) study and has received peer-reviewed grant funding from the Irish Higher Education Authority. LIBRA aims to use simulation-based education to develop a gender equality leadership training program for student leaders in higher education. The findings will be summarized in tabular form, and a narrative synthesis produced to inform curriculum development. CONCLUSIONS: This review seeks to inform curriculum design by reporting on the gender equality-enabling skills and leadership skills necessary to foster gender equality. This paper should inform recommendations for training and catalyze future research in this rapidly evolving area. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/44584.

Critical design choices in healthcare simulation education: a 4C/ID perspective on design that leads to transfer.

BACKGROUND: Healthcare simulation education often aims to promote transfer of learning: the application of knowledge, skills, and attitudes acquired during simulations to new situations in the workplace. Although achieving transfer is challenging, existing theories and models can provide guidance. RECOMMENDATIONS: This paper provides five general recommendations to design simulations that foster transfer: (1) emphasize whole-task practice, (2) consider a cognitive task analysis, (3) embed simulations within more comprehensive programs, (4) strategically combine and align simulation formats, and (5) optimize cognitive load. We illustrate the application of these five recommendations with a blueprint for an educational program focusing on simulation activities. CONCLUSIONS: More evidence-informed approaches to healthcare simulation might require a paradigm shift. We must accept that a limited number of simulations is not enough to develop complex skills. It requires comprehensive programs that combine simulation sessions with workplace learning.

A Mixed Methods Study Identifying the Competencies of Health Care Simulation Technicians.

INTRODUCTION: Health care simulation technicians (HSTs), also referred to as simulation operations specialists, are essential to the delivery of simulation-based education. The HST role draws on a broad range of knowledge, skills, and attitude competencies. However, because of the neoteric nature of the HST role and the ambiguity surrounding the core responsibilities of the position, it has proved difficult to identify the competencies required to perform this role successfully. This study aims to identify the knowledge, skills, and attitude competencies required by HSTs. METHODS: A mixed methods approach was used in this study. Data were collected from (1) online searches of HST job descriptions and (2) semistructured interviews about the competencies required by HSTs with 10 HSTs, 10 health care simulation educators, and 10 health care simulation center managers/director. The data from the job descriptions and interviews were analyzed using thematic analysis, using a framework method to guide the coding. RESULTS: A total of 59 competencies were identified from the job descriptions and 65 competencies from the interviews. This analysis resulted in the identification of 9 competency domains: 3 knowledge domains (technical, clinical, and pedagogic), 4 skills domains (resourcefulness, pedagogic, team, and technical), and 2 attitudes domains (professional and "can-do" mentality). CONCLUSIONS: The identification of the competencies required by HSTs will support the selection of candidates with the attributes that will allow them to be successful in this role and guide continuous professional development opportunities for current and future HSTs.

Preparing for Pediatrics: Experiential Learning Helps Medical Students Prepare for Their Clinical Placement.

Despite the importance of effective communication skills in pediatrics, clinical placements may inadequately prepare undergraduate students to communicate with children. The integration of non-clinical interactions with healthy children within a pediatric curriculum has the potential to enhance learning. We designed and implemented a novel course involving experiential learning, including video-recorded consultations with simulated parents (SPs), team-based scenarios with a pediatric mannequin, interactions with healthy children through a pre-school visit and medical student led health workshops for primary school children. Medical students at the RCSI University of Medicine and Health Sciences took part in the course. We used a mixed methods approach to assess the impact of the course. We investigated medical students' perspectives through a pre- and post-intervention questionnaire and post-intervention focus group discussions (FGDs). We assessed participating children's health literacy at the start of the course. 144/279 (51.6%) of the fourth year medical student cohort on their pediatric rotation, consented to participate in the study. All 144 (100%) of consenting students completed the pre-intervention questionnaire. 59/144 (40.1%) of consenting students completed the post-intervention questionnaire. Results showed a statistically significant improvement in ratings (p < 0.05) for items related to managing a confrontational situation involving family members, completing a psychosocial assessment with an adolescent and effectiveness using evidence-based medicine (EBM) when motivating patients. There was a statistically significant decrease in how students rated their comfort at using EBM when motivating patients. Four themes relating to how students experienced the intervention were identified from eight FGDs (n = 35 students): Shaping Student Learning; Supporting Student Learning; Developing New Skills and Feeling More Prepared. 39/49 (79.6%) children completed a health literacy assessment. All questions had a high percentage of positive responses. Question 7, understanding your doctor, had the highest proportion of negative responses (27%). Ours is one of the first studies to design an educational intervention to enhance pediatrics teaching by combining interactions with healthy children outside of a clinical setting with more traditional simulation-based approaches. We conclude that this type of intervention supports students' learning of pediatric communication skills and enhances students' perceived preparation for clinical placement.

Their OSCE, not your Oscar: Simulated Patients' Perspectives.

INTRODUCTION: Simulated patients (SPs) are involved widely in the support of health care education for communication and consultation skills teaching. This study aimed to explore SPs' perspectives of their role and contribution to health professions education. METHODS: A qualitative approach was used. Twenty-two SPs (actor and non-actor) involved in teaching at the Royal College of Surgeons Ireland (RCSI) participated in one of four focus groups, which were audiorecorded. Two focus groups involved professional actors (n = 7), and two focus groups involved non-actor SPs (n = 15). Transcribed data were analysed using thematic analysis. RESULTS: The first theme 'Reward of Contribution' highlights how the SP role is situated in a position of mutual benefit for both SP and student. The second theme 'Multiple Personas' demonstrates the complexity of SP role portrayal. The third theme 'Culture and Communication' is a new finding and demonstrates the role SPs feel they have in helping to change the culture of health care practice. The fourth theme 'A touchy subject' addresses the preferences of SPs concerning involvement in both intimate and nonintimate physical examination. CONCLUSIONS: SPs believe they have an important role to play in health care education and they also learn from their involvement. SPs' perspectives need to be considered to ensure they feel supported in their role and that their unique insights remain beneficial for student learning.

Evaluation of medical student retention of clinical skills following simulation training.

BACKGROUND: Adequate clinical skills training is a challenge for present day medical education. Simulation Based Education (SBE) is playing an increasingly important role in healthcare education worldwide to teach invasive procedures. The impact of this teaching on students along with retention of what is taught is not fully understood. The purpose of this study was to evaluate the retention levels of practical skills taught and assessed by SBE and to explore the degree of re-training required to restore decayed performance. In exploring this aim, the study further investigates how skilled performance decays over time and which dimensions of clinical skills were more likely to decay. METHODS: Study participants were 51 final year medical students. They were provided with online pre-course videos and procedural guides asynchronously with repeatedly access. 7 of the skills taught over 2 years using task trainers were selected. Following demonstration from faculty, students practiced in small groups with faculty facilitated supervision and peer support prior to formal testing. Score sheets with itemised procedure checklists detailing the minimum passing standard (MPS) for each skill were designed. To test retention of skills, 18 months later, there was an unannounced test to demonstrate proficiency in the skills. Students were asked to complete a questionnaire indicating how many times and where they had practiced or performed the skills. RESULTS: 55% of the students were deficient in 3 or more skills and 4% were not competent in 5 or more skills. A significant number of students had never practiced some skills following the initial teaching session. A relationship was noted with the number of times students self-declared that they had practiced and their performance. Decay is evident in both psychomotor and cognitive domains of the skills. CONCLUSION: A curriculum with deliberate practice significantly increases the competence of students in defined clinical skills. Deliberate practice of clinical skills, under supervision of an engaged instructor, is a key component of the mastery model. Experiences and assessments in the clinical setting need to be augmented with focus on direct observation and focused feedback to reinforce the skills acquired in the simulated setting.

How Anesthetic, Analgesic and Other Non-Surgical Techniques During Cancer Surgery Might Affect Postoperative Oncologic Outcomes: A Summary of Current State of Evidence.

The question of whether anesthetic, analgesic or other perioperative intervention during cancer resection surgery might influence long-term oncologic outcomes has generated much attention over the past 13 years. A wealth of experimental and observational clinical data have been published, but the results of prospective, randomized clinical trials are awaited. The European Union supports a pan-European network of researchers, clinicians and industry partners engaged in this question (COST Action 15204: Euro-Periscope). In this narrative review, members of the Euro-Periscope network briefly summarize the current state of evidence pertaining to the potential effects of the most commonly deployed anesthetic and analgesic techniques and other non-surgical interventions during cancer resection surgery on tumor recurrence or metastasis.

Evaluation of simulation methods for teaching peripheral arterial examination to medical students.

Physical examination is a critical component of medical practice yet the focus on efficient patient turnover has impacted the availability of patients with clinical findings willing to be examined by students and skills' teaching is not consistent across clinical rotations. This work evaluates simulation methodologies for teaching of the peripheral arterial examination and evaluates whether skills learnt are transferable to clinical practice. Second-year medical students were taught peripheral arterial examination on a SimMan 3G or with simulated patients (SPs). Both groups were assessed by Objective Structured Clinical Examination (OSCE) with outpatients who have been diagnosed with peripheral arterial disease. There was no difference in the pass rate at OSCE between the two groups. SimMan better facilitated repeated practice, group learning, peer teaching and discussion, which were highly valued by the students. Students felt that the SImMan tutorial did not facilitate development of spatial cognition or pattern recognition. They also felt less well prepared to deal with real patients in terms of having practised appropriate language, issuing instructions and attempting to reassure patients. Both methods of simulation teaching have distinct merits and the ideal approach maybe to use the SimMan in combination with SPs.

Protective role of cyclooxygenase (COX)-2 in experimental lung injury: evidence of a lipoxin A4-mediated effect.

BACKGROUND: Polymorphoneutrophils (PMNs) are activated by inflammatory mediators following splanchnic ischemia/reperfusion (I/R), potentially injuring organs such as the lung. As a result, some patients develop respiratory failure following abdominal aortic aneurysm repair. Pulmonary cyclooxygenase (COX)-2 protects against acid aspiration and bacterial instillation via lipoxins, a family of potent anti-inflammatory lipid mediators. We explored the role of COX-2 and lipoxin A(4) in experimental I/R-mediated lung injury. MATERIALS AND METHODS: Sprague-Dawley rats were assigned to one of the following five groups: (1) controls; (2) aortic cross-clamping for 45 min and reperfusion for 4 h (I/R group); (3) I/R and SC236, a selective COX-2 inhibitor; (4) I/R and aspirin; and (5) I/R and iloprost, a prostacyclin (PGI(2)) analogue. Lung injury was assessed by wet/dry ratio, myeloperoxidase (MPO) activity, and bronchoalveolar lavage (BAL) neutrophil counts. BAL levels of thromboxane, PGE(2), 6-keto-PGF(1)α (a hydrolysis product of prostacyclin), lipoxin A(4), and 15-epi-lipoxin A(4) were analyzed by enzyme immunoassay (EIA). Immunostaining for COX-2 was performed. RESULTS: I/R significantly increased tissue MPO, the wet/dry lung ratio, and neutrophil counts. These measures were significantly further aggravated by SC236 and improved by iloprost. I/R increased COX-2 immunostaining and both PGE(2) and 6-keto-PGF(1α) levels in BAL. SC236 markedly reduced these prostanoids and lipoxin A(4) compared with I/R alone. Iloprost markedly increased lipoxin A(4) levels. The deleterious effect of SC236 and the beneficial effect of iloprost was associated with a reduction and an increase, respectively, in lipoxin A(4) levels. CONCLUSIONS: Lipoxin A(4) warrants further evaluation as a mediator of COX-2 regulated lung protection.

α-1 Antitrypsin regulates human neutrophil chemotaxis induced by soluble immune complexes and IL-8.

Hereditary deficiency of the protein α-1 antitrypsin (AAT) causes a chronic lung disease in humans that is characterized by excessive mobilization of neutrophils into the lung. However, the reason for the increased neutrophil burden has not been fully elucidated. In this study we have demonstrated using human neutrophils that serum AAT coordinates both CXCR1- and soluble immune complex (sIC) receptor-mediated chemotaxis by divergent pathways. We demonstrated that glycosylated AAT can bind to IL-8 (a ligand for CXCR1) and that AAT-IL-8 complex formation prevented IL-8 interaction with CXCR1. Second, AAT modulated neutrophil chemotaxis in response to sIC by controlling membrane expression of the glycosylphosphatidylinositol-anchored (GPI-anchored) Fc receptor FcγRIIIb. This process was mediated through inhibition of ADAM-17 enzymatic activity. Neutrophils isolated from clinically stable AAT-deficient patients were characterized by low membrane expression of FcγRIIIb and increased chemotaxis in response to IL-8 and sIC. Treatment of AAT-deficient individuals with AAT augmentation therapy resulted in increased AAT binding to IL-8, increased AAT binding to the neutrophil membrane, decreased FcγRIIIb release from the neutrophil membrane, and normalization of chemotaxis. These results provide new insight into the mechanism underlying the effect of AAT augmentation therapy in the pulmonary disease associated with AAT deficiency.

Taurine modulates neutrophil function but potentiates uropathogenic E. coli infection in the murine bladder.

Eradication of a urinary tract infection (UTI) appears to be related to a number of innate host defence mechanisms and their interactions with invading bacteria. Recurrent UTIs (rUTIs) pose a difficult problem in that these bacteria use both host and bacterial factors to evade elimination. Neutrophil bactericidal function is depressed, both systemically and in urine, in patients with a history of recurrent UTI. Taurine is a semi-essential amino acid and is successful in preserving neutrophil bactericidal function in urine. Taurine may preserve neutrophil function at the urothelium and thus aid UTI resolution. Adult female (6 weeks old) C57Bl/6 mice were randomised into three groups: a saline gavage only control group, a saline gavage + E. coli group, and a taurine gavage + E. coli group [21 g/70 kg taurine in 0.9% normal saline (N/S) for 5 days]. Whilst taurine gavage pre-treatment resulted in increased serum neutrophils respiratory burst activity, at the urothelial-endothelial interface it caused higher colony forming units in the urine and a higher incidence of E. coli invasion in the bladder wall with no evidence of increased bladder wall neutrophils infiltration on MPO assay of histological assessment. Histologically there was also evidence of reduced bladder inflammation and urothelial cell apoptosis. In conclusion, taurine effectively increases neutrophils activity but given its anti-inflammatory properties, at the expense of decreased urothelial-endothelial activation thus preventing clearance of active E. coli infection in the bladder. Despite the negative results, this study demonstrates the importance of modulating interactions at the urothelial interface.