The implementation of simulation-based training (SBT) to teach flexible bronchoscopy (FB) skills to novice trainees has increased during the last decade. However, it is unknown whether SBT is effective to teach FB to novices and which instructional features contribute to training effectiveness. How effective is FB SBT and which instructional features contribute to training effectiveness? We searched Embase, PubMed, Scopus, and Web of Science for articles on FB SBT for novice trainees, considering all available literature until November 10, 2022. We assessed methodological quality of included studies using a modified version of the Medical Education Research Study Quality Instrument, evaluated risk of bias with relevant tools depending on study design, assessed instructional features, and intended to correlate instructional features to outcome measures. We identified 14 studies from an initial pool of 544 studies. Eleven studies reported positive effects of FB SBT on most of their outcome measures. However, risk of bias was moderate or high in eight studies, and only six studies were of high quality (modified Medical Education Research Study Quality Instrument score ≥ 12.5). Moreover, instructional features and outcome measures varied highly across studies, and only four studies evaluated intervention effects on behavioral outcome measures in the patient setting. All of the simulation training programs in studies with the highest methodological quality and most relevant outcome measures included curriculum integration and a range in task difficulty. Although most studies reported positive effects of simulation training programs on their outcome measures, definitive conclusions regarding training effectiveness on actual bronchoscopy performance in patients could not be made because of heterogeneity of training features and the sparse evidence of training effectiveness on validated behavioral outcome measures in a patient setting. PROSPERO; No.: CRD42021262853; URL: https://www.crd.york.ac.uk/prospero/.

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.

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 (P<0.001), except for the number of wall contacts per minute of PT (4.3 [IQR 3.0 to 6.2] pre vs. 3.5 [IQR 2.6 to 5.3] post, P=0.07). For task 2, PT was reduced by 54% (10.3±2.7 minutes pre vs. 4.7±0.9 minutes post, P<0.001) with an improvement in overall-competence scores (2.0 [IQR 1.0 to 2.0] pre vs. 4.0 [IQR 4.0 to 5.0] post, P<0.001) and all dexterity parameters (P<0.001). Conclusion: Nationwide implementation of a SBT course led to rapid improvement of residents’ basic bronchoscopy skills while halving PT.

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.

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.