Eveline Charlotte Françoise Gerretsen

Simulation-based training can be valuable for teaching bronchoscopy to intensivists, providing a risk-free training environment. We developed, implemented and evaluated a simulation-based flexible bronchoscopy training program for intensive care Fellows and intensivists. This paper presents the development of its design and lessons learned. We used the Analyse, Design, Develop, Implement and Evaluate model for developing and evaluating the training program (Analysis and Design – phase 1, Development – phase 2, Implementation – phase 3, Evaluation – phase 4). In phase 1, two intensivists formulated learning objectives for bronchoscopy in an intensive care setting, which guided the identification and development of training materials and the preliminary training program (phase 2). In phase 3, we tested this program and gathered feedback from participants to guide program modifications. After implementing the adjusted training, we measured participants’ satisfaction using a survey based on closed- and open-ended questions (phase 4). Fifty-seven participants attended the training, with 18 (32%) responding to the questionnaire. Respondents highly appreciated the training program, with median satisfaction scores of 4 or higher on a five-point scale for all closed-ended questions. Respondents appreciated the supervision and feedback and found the simulator equipment relevant for learning bronchoscopy. This description of the program’s development and its evaluation results can serve as a valuable resource for those wishing to establish similar training programs. We recognise that further implementation of evidence-based instructional design principles might enhance the training program’s scientific foundation and effectiveness. We therefore recommend a more evidence-based approach for the design of future bronchoscopy simulation training programs.

Introduction: Simulation-based training (SBT) is a key method for teaching bronchoscopy skills to pulmonology residents. A theoretical foundation can enhance SBT efficiency. This study developed and evaluated the validity of an anatomy and theoretical bronchoscopy exam using Kane’s validity framework. Methods: Nineteen anatomy and 58 theoretical exam questions, developed by pulmonology experts, were assessed through two Delphi rounds. Both exams were then taken by 53 prepared pulmonology residents. The theoretical exam was also taken by three unprepared groups: novices, intermediates, and experts. Using the residents’ data, scoring evidence for the theoretical exam was evaluated using item difficulty and item discrimination indices, and generalization evidence was assessed using Cronbach’s alpha. Extrapolation evidence was obtained by comparing theoretical exam scores across the different groups. Implications evidence for both exams was gathered by evaluating residents’ preparedness, based on exam performance and instructor feedback. Results: The Delphi procedure resulted in 19 anatomy and 31 theoretical questions. Item difficulty values predominantly ranged from 0.85 to 1.0; item discrimination indices mostly ranged from 0.0 to 0.25. Cronbach’s alpha was 0.55. While scores appeared to correlate with experience, no significant differences were observed between the four groups. Most residents passed both exams on their first attempt, and instructors rated their anatomical knowledge as good. Conclusion: Expert involvement and acceptable item difficulty, item discrimination, and internal consistency supported the exams’ validity. The exams also effectively motivated residents to prepare for SBT. These findings highlight the value of pre-SBT exams in enhancing residents’ preparation, allowing more time to focus on mastering procedural skills.

Background: In 2020, a mandatory, nationwide 1-day bronchoscopy simulation-based training (SBT) course was implemented for novice pulmonology residents in the Netherlands. This pretest–posttest study was the first to evaluate the effectiveness of such a nationwide course in improving residents’ simulated basic bronchoscopy skills. Methods: After passing a theoretical test, residents followed a 1-day SBT course, available in 7 centers, where they practiced their bronchoscopy skills step-by-step on a virtual reality simulator under pulmonologist supervision. Residents practiced scope handling efficiency (task 1) and navigational skills combined with lung anatomy knowledge (task 2). Task 1 outcome measures were navigational skill simulator metrics: percentage of time at mid-lumen, percentage of time with scope-wall contact, procedure time (PT), number of wall contacts and number of wall contacts per minute of PT. Task 2 outcome measures were PT, observational assessment scores of a validated tool with a 5-point scale (1 representing the worst and 5 the best competence) and blinded dexterity assessments. Results: The study included 100 residents. All outcome measures of task 1 improved significantly (PP=0.07). For task 2, PT was reduced by 54% (10.3±2.7 minutes pre vs. 4.7±0.9 minutes post, PPP<0.001). Conclusion: Nationwide implementation of a SBT course led to rapid improvement of residents’ basic bronchoscopy skills while halving PT.

Background and aim: Bronchoscopy simulation studies often use a pre-test post-test design. However, a drawback of this design is a possible testing effect, resulting in an overestimation of intervention effects. We evaluated the effect of pre-testing on post-test bronchoscopy simulation performance. Methods: Undergraduate medical students without any bronchoscopy experience were recruited for this study through flyers on campus. Twenty students participated between November 2021 and October 2022. Participants performed 2 simulator tasks in the morning (the pre-test). After a 4-6 hour break, participants performed the same 2 tasks (the post-test). The tasks comprised “Task 1” (assessing navigational skills) and “Task 3” (assessing navigational skills in a realistic anatomical environment). Outcome measures were simulator metrics for Task 1 and validated assessment tool scores (adapted from Konge, L. et al. Respiration 2012; 83:53-60) and time for Task 3. The tool consisted of 7 parameters leading to an overall score on a 5-point scale (1 representing the worst and 5 the best performance). Results: Results showed on average a 40% reduction in wall contacts for Task 1 (P<.001) and a reduction in time needed for Task 1 (57 ± 15 seconds pre versus 38 ± 12 seconds post, P<.001) and Task 3 (5.3 ± 1.3 minutes pre versus 4.4 ± 1.0 minutes post, P<.001). Overall assessment tool scores did not improve (pre 2.0[1.0], post 2.0[0.0], P=0.4). Conclusion: A significant testing effect was observed for navigational skills in general and in a realistic anatomical environment. Future pre-post-test bronchoscopy simulation studies should correct their effect sizes taking into account the size of this testing effect.

The SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) protein syntaxin-5 (Stx5) is essential for Golgi transport. In humans, the STX5 mRNA encodes two protein isoforms, Stx5 Long (Stx5L) from the first starting methionine and Stx5 Short (Stx5S) from an alternative starting methionine at position 55. In this study, we identify a human disorder caused by a single missense substitution in the second starting methionine (p.M55V), resulting in complete loss of the short isoform. Patients suffer from an early fatal multisystem disease, including severe liver disease, skeletal abnormalities and abnormal glycosylation. Primary human dermal fibroblasts isolated from these patients show defective glycosylation, altered Golgi morphology as measured by electron microscopy, mislocalization of glycosyltransferases, and compromised ER-Golgi trafficking. Measurements of cognate binding SNAREs, based on biotin-synchronizable forms of Stx5 (the RUSH system) and Förster resonance energy transfer (FRET), revealed that the short isoform of Stx5 is essential for intra-Golgi transport. Alternative starting codons of Stx5 are thus linked to human disease, demonstrating that the site of translation initiation is an important new layer of regulating protein trafficking.

The prognosis and responsiveness to chemotherapy and checkpoint inhibitors differs substantially among patients with bladder cancer (BC). There is an unmet need for biomarkers that can accurately predict prognosis and treatment outcome. Here, we describe the available literature on the prognostic and predictive value of tumor-infiltrating immune cells in BC. Current evidence indicates that a high density of tumor-infiltrating CD8⁺ T cells is a favorable prognostic factor, whereas PD-L1 expression and tumor-associated macrophages are unfavorable prognostic features. While PD-L1 expression appears unsuccessful as a biomarker for the response to checkpoint inhibitors, there are some indications that high CD8⁺ T cell infiltration, low transforming growth factor-beta signaling and low densities of myeloid-derived suppressor cells are associated with response. Future studies should focus on combinations of biomarkers to accurately predict survival and response to treatment.

The SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) protein syntaxin-5 (Stx5) is essential for Golgi transport. In humans, the STX5 mRNA encodes two protein isoforms, Stx5 Long (Stx5L) from the first starting methionine and Stx5 Short (Stx5S) from an alternative starting methionine at position 55. In this study, we identify a human disorder caused by a single missense substitution in the second starting methionine (p.M55V), resulting in complete loss of the short isoform. Patients suffer from an early fatal multisystem disease, including severe liver disease, skeletal abnormalities and abnormal glycosylation. Primary human dermal fibroblasts isolated from these patients show defective glycosylation, altered Golgi morphology as measured by electron microscopy, mislocalization of glycosyltransferases, and compromised ER-Golgi trafficking. Measurements of cognate binding SNAREs, based on biotin-synchronizable forms of Stx5 (the RUSH system) and Förster resonance energy transfer (FRET), revealed that the short isoform of Stx5 is essential for intra-Golgi transport. Alternative starting codons of Stx5 are thus linked to human disease, demonstrating that the site of translation initiation is an important new layer of regulating protein trafficking.