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Antibodies to programmed cell death protein1 (anti-PD-1) have become a promising immunotherapy for triple negative breast cancer (TNBC), blocking PD-L1 signaling from pro-tumor cells through T cell PD-1 receptor binding. Nevertheless, only 10-20% of PD-L1 + metastatic TNBC patients who meet criteria benefit from ICB, and biomarkers to predict patient response have been elusive. We have previously developed an immunological niche, consisting of a microporous implant in the subcutaneous space, that supports tissue formation whose immune composition is consistent with that within vital organs. Herein, we investigated dynamic gene expression within this immunological niche to provide biomarkers of response to anti-PD-1. In a 4T1 model of metastatic TNBC, we observed sensitivity and resistance to anti-PD-1 based on primary tumor growth and survival. The niche was biopsied before, during, and after anti-PD-1 therapy, and analyzed for cell types and gene expression indicative of treatment refractivity. Myeloid cell-to-lymphocyte ratios were altered between ICB-sensitivity and resistance. Longitudinal analysis of gene expression implicated dynamic myeloid cell function that stratified sensitivity from resistance. A niche-derived gene signature predicted sensitivity or resistance prior to therapy. Analysis of the niche to monitor immunotherapy response presents a new opportunity to personalize care and investigate mechanisms underlying treatment resistance., Competing Interests: Conflict of Interest Statement: L.D.S. and J.S.J. consult and have financial interests in COUR Pharmaceutical Development, Inc.

Background: Hemorrhage is the leading cause of preventable death after trauma. In high-income countries first responders are trained in hemorrhage control techniques but this is not the case for developing countries like Guatemala. We present a low-cost training model for tourniquet application using a combination of virtual and physical components., Methods: The training program includes a mobile application with didactic materials, videos and a gamified virtual reality environment for learning. Additionally, a physical training model of a bleeding lower extremity is developed allowing learners to practice tourniquet application using inexpensive and accessible materials. Validation of the simulator occurred through content and construct validation. Content validation involved subjective assessments by novices and experts, construct validation compared pre-training novices with experts. Training validation compared pre and post training novices for improvement., Results: Our findings indicate that users found the simulator useful, realistic, and satisfactory. We found significant differences in tourniquet application skills between pre-training novices and experts. When comparing pre- and post-training novices, we found a significantly lower bleeding control time between the groups., Conclusion: This study suggests that this training approach can enhance access to life-saving skills for prehospital personnel. The inclusion of self-assessment components enables self-regulated learning and reduces the need for continuous instructor presence. Future improvements involve refining the tourniquet model, validating it with first-responder end users, and expanding the training program to include other skills., (© 2024 International Society of Surgery/Société Internationale de Chirurgie (ISS/SIC).)

The landscape of surgical training is rapidly evolving with the advent of artificial intelligence (AI) and its integration into education and simulation. This manuscript aims to explore the potential applications and benefits of AI-assisted surgical training, particularly the use of large language models (LLMs), in enhancing communication, personalizing feedback, and promoting skill development. We discuss the advancements in simulation-based training, AI-driven assessment tools, video-based assessment systems, virtual reality (VR) and augmented reality (AR) platforms, and the potential role of LLMs in the transcription, translation, and summarization of feedback. Despite the promising opportunities presented by AI integration, several challenges must be addressed, including accuracy and reliability, ethical and privacy concerns, bias in AI models, integration with existing training systems, and training and adoption of AI-assisted tools. By proactively addressing these challenges and harnessing the potential of AI, the future of surgical training may be reshaped to provide a more comprehensive, safe, and effective learning experience for trainees, ultimately leading to better patient outcomes. .

Purpose: Nearly 200,000 laparoscopic Roux-en-Y gastric bypass (LRYGB) are performed yearly. Reported learning curves range between 50 and 150, even 500 cases to decrease the operative risk. Simulation programs could accelerate this learning curve safely; however, trainings for LRYGB are scarce. This study aims to describe and share our 5-year experience of a simulated program designed to achieve proficiency in LRYGB technical skills., Materials and Methods: A quasi-experimental design was used. All recruited participants were previously trained with basic and advanced laparoscopic simulation curriculum completing over 50 h of practical training. Ex vivo animal models were used to practice manual and stapled gastrojejunostomy (GJ) and stapled jejunojejunostomy (JJO) in 10, 3, and 4 sessions, respectively. The main outcome was to assess the manual GJ skill acquisition. Pre- and post-training assessments using a Global Rating Scale (GRS; max 25 pts), Specific Rating Scale (SRS; max 20 pts), performance time, permeability, and leakage rates were analyzed. For the stapled GJ and JJO, execution time was registered. Data analysis was performed using parametric tests., Results: In 5 years, 68 trainees completed the program. For the manual GJ's pre- vs post-training assessment, GRS and SRS scores increased significantly (from 17 to 24 and from 13 to 19 points respectively, p-value < 0.001). Permeability rate increased while leakage rate and procedural time decreased significantly., Conclusion: This simulated training program showed effectiveness in improving laparoscopic skills for manual GJ and JJO in a simulated scenario. This new training program could optimize the clinical learning curve. Further studies are needed to assess the transfer of skills to the operating room., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: A limitation to expanding laparoscopic simulation training programs is the scarcity of expert evaluators. In 2019, a new digital platform for remote and asynchronous laparoscopic simulation training was validated. Through this platform, 369 trainees have been trained in 14 institutions across Latin America, collecting 6729 videos of laparoscopic training exercises. The use of artificial intelligence (AI) has recently emerged in surgical simulation, showing usefulness in training assessment, virtual reality scenarios, and laparoscopic virtual reality simulation. An AI algorithm to assess basic laparoscopic simulation training exercises was developed. This study aimed to analyze the agreement between this AI algorithm and expert evaluators in assessing basic laparoscopic-simulated training exercises., Methods: The AI algorithm was trained using 400-bean drop (BD) and 480-peg transfer (PT) videos and tested using 64-BD and 43-PT randomly selected videos, not previously used to train the algorithm. The agreement between AI and expert evaluators from the digital platform (EE) was then analyzed. The exercises being assessed involve using laparoscopic graspers to move objects across an acrylic board without dropping any objects in a determined time (BD < 24 s, PT < 55 s). The AI algorithm can detect object movement, identify if objects have fallen, track grasper clamps location, and measure exercise time. Cohen's Kappa test was used to evaluate the agreement between AI assessments and those performed by EE, using a pass/fail nomenclature based on the time to complete the exercise., Results: After the algorithm was trained, 79.69% and 93.02% agreement were observed in BD and PT, respectively. The Kappa coefficients test observed for BD and PT were 0.59 (moderate agreement) and 0.86 (almost perfect agreement), respectively., Conclusion: This first approach of AI use in basic laparoscopic skills simulated training assessment shows promising results, providing a preliminary framework to expand the use of AI to other basic laparoscopic skills exercises., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Limitations in surgical simulation training include lack of access to validated training programs with continuous year-round training and lack of experts' ongoing availability for feedback. A model of simulation training was developed to address these limitations. It incorporated basic and advanced laparoscopic skills curricula from a previously validated program and provided instruction through a digital platform. The platform allowed for remote and asynchronous feedback from a few trained instructors. The instructors were continuously available and provided personalized feedback using a variety of different media. We describe the upscaling of this model to teach trainees at fourteen centers in eight countries., Methods: Institutions with surgical programs lacking robust simulation curricula and needing instructors for ongoing education were identified. The simulation centers ("skills labs") at these sites were equipped with necessary simulation training hardware. A remote training-the-administrators (TTA) program was developed where personnel were trained in how to manage the skills lab, schedule trainees, set up training stations, and use the platform. A train-the-trainers (TTT) program was created to establish a network of trained instructors, who provided objective feedback through the platform remotely and asynchronously., Results: Between 2019 and 2022, seven institutions in Chile and one in each of the USA, Bolivia, Brazil, Ecuador, El Salvador, México, and Perú implemented a digital platform-based remote simulation curriculum. Most administrators were not physicians (19/33). Eight Instructors were trained with the TTT program and became active proctors. The platform has been used by 369 learners, of whom 57% were general surgeons and general surgery residents. A total of 6729 videos, 28,711 feedback inputs, and 233.7 and 510.2 training hours in the basic and advanced programs, respectively, were registered., Conclusion: A remote and asynchronous method of giving instruction and feedback through a digital platform has been effectively employed in the creation of a robust network of continuous year-round simulation-based training in laparoscopy. Training centers were successfully run only with trained administrators to assist in logistics and setup, and no on-site instructors were necessary., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The advantages of laparoscopic surgery over traditional open surgery have changed the surgical education paradigm in the past 20 years. Among its benefits are an improvement in clinical outcomes and patient safety, becoming the standard in many surgical procedures. However, it encompasses an additional challenge due to the complexity to achieve the desired competency level. Simulation-based training has emerged as a solution to this problem. However, there is a relative scarcity of experts to provide personalized feedback. Technology-Enhanced Learning could be a valuable aid in personalizing the learning process and overcoming geographic and time-related barriers that otherwise would preclude the training to happen. Currently, various educational digital platforms are available, but none of them is able to successfully provide personalized feedback., Aims: The aim of this study was to develop and test a proof of concept of a novel Technology-Enhanced Learning laparoscopic skills platform with personalized remote feedback., Methods: The platform "Lapp," a web and mobile cloud-based solution, is proposed. It consists of a web and mobile application where teachers can evaluate remotely and asynchronously exercises performed by students, adding personalized feedback for trainees to achieve a learning curve wherever and whenever they train. To assess the effectiveness of this platform, two groups of students were compared: 130 participants received in-person feedback and 39 participants received remote asynchronous feedback throughout the application., Results: The results showed no significant differences regarding competency levels among both groups., Conclusion: A novel Technology-Enhanced Learning strategy consisting of remote asynchronous feedback throughout Lapp facilitates and optimizes learning, solving traditional spatiotemporal limitations.

Purpose: To date, there are no training programs for basic suturing that allow remote deliberate practice. This study seeks to evaluate the effectiveness of a basic suture skills training program and its 6-month skill retention applying unsupervised practice and remote digital feedback., Methods: Fourth-year medical-student trainees reviewed instructional videos from a digital platform and performed unsupervised practice as needed at their homes. When they felt competent, trainees uploaded a video of themselves practicing the skill. In < 72 h, they received expert asynchronous digital feedback. The course had two theoretical stages and five video-based assessments, where trainees performed different suturing exercises. For the assessment, a global (GRS) and specific rating scale (SRS) were used, with a passing score of 20 points (max:25) and 15 (max:20), respectively. Results were compared to previously published work with in-person expert feedback (EF) and video-guided learning without feedback (VGL). A subgroup of trainees underwent a 6-month skills retention assessment., Results: Two-hundred and forty-three trainees underwent the course between March and December 2021. A median GRS of 24 points was achieved in the final assessment, showing significantly higher scores ( p  < 0.001) than EF and VGL (20.5 and 15.5, respectively). Thirty-seven trainees underwent a 6-month skills retention assessment, improving in GRS (23.38 vs 24.03, p value = 0.06) and SRS (18.59 vs 19, p value = 0.07)., Conclusion: It is feasible to teach basic suture skills to undergraduate medical students using an unsupervised training course with remote and asynchronous feedback through a digital platform. This methodology allows continuous training with the repetition of quality practice, personalized feedback, and skills retention at 6 months., Competing Interests: Conflict of interestSlavka Chelebifski, Catalina Ortiz, Cristián Jarry, Valentina Durán, Adnan Alseidi, Elga Zamorano, Fernando Pimentel, and Fernando Crovari have nothing to disclose., (© The Author(s), under exclusive licence to Association for Surgical Education 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Three-dimensional printing (3DP) has recently gained importance in the medical industry, especially in surgical specialties. It uses different techniques and materials based on patients' needs, which allows bioprofessionals to design and develop unique pieces using medical imaging provided by computed tomography (CT) and magnetic resonance imaging (MRI). Therefore, the Department of Biology and Medicine and the Department of Physics and Engineering, at the Bioastronautics and Space Mechatronics Research Group, have managed and supervised an international cooperation study, in order to present a general review of the innovative surgical applications, focused on anatomical systems, such as the nervous and craniofacial system, cardiovascular system, digestive system, genitourinary system, and musculoskeletal system. Finally, the integration with augmented, mixed, virtual reality is analyzed to show the advantages of personalized treatments, taking into account the improvements for preoperative, intraoperative planning, and medical training. Also, this article explores the creation of devices and tools for space surgery to get better outcomes under changing gravity conditions., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 José Cornejo et al.)

Background: Simulation training is a validated method for acquiring laparoscopic skills. Training sessions may be sporadic or lack continuity in oversight by instructors since traditional programs mandate in-person teaching and evaluation. This study presents the development, implementation, and results of a novel smartphone application that enables remote teacher-student interaction. This interface is used to complete a validated program that provides learner-specific feedback. Outcomes of training via Lapp were compared to outcomes of traditional in-person training., Methods: A web-based and mobile iOS and Android application (Lapp) was developed to enable a remote student-teacher interaction. Instructors use Lapp to assess video recorded training sessions of students at distant locations and guide them through the laparoscopic skill course with specific and personalized feedback. Surgical trainees at two remote training centers were taught using Lapp. A control group was assessed during traditional simulation training at the training facility, with in-person feedback. Pre- and post-training performances were video recorded for each trainee and blindly evaluated by two experts using a global rating scale (GRS) and a specific rating scale (SRS)., Results: A total of 30 trainees were trained via Lapp and compared with 25 locally taught. Performance in the Lapp group improved significantly after the course in both GRS and SRS scores, from 15 [6-17] to 23 [20-25], and from 12 [11-15] to 18 [15-20], respectively. The results between both groups were comparable., Conclusion: Laparoscopic simulation training using a mobile app is as effective as in-person instruction in teaching advanced laparoscopic surgical skills. Lapp provides an effective method of teaching through simulation remotely and may allow expansion of robust simulation training curriculums.

Background: Simulation training is a validated, highly effective tool for learning laparoscopy. Feedback plays a crucial role in motor skills training. We present an app to guide students during advanced laparoscopy simulation training and evaluate its effect on training., Methods: A smartphone(iOS)-app was developed. A group of trainees were randomized to use the app (YAPP) or not use the app (NAPP). We used blinded analysis with validated rating scales to assess their performance before and after the training. The number of requests for tutor feedback per session was recorded. Finally, the participants in the YAPP group completed a survey about their experience with the app., Results: Fifteen YAPP and 10 NAPP completed the training program. There were no statistically significant differences between their skills performance scores (P = .338). The number of tutor feedback requests in the YAPP and NAPP was of 4 (3-6) and 13 (10-14) (P < .001), respectively. All participants in the YAPP group found the app was useful., Conclusion: The use of a smartphone app reduces the need for expert tutor feedback without decreasing the degree of skills acquisition., (© 2019 The Authors.)

In recent years, an increase of uropathogenic Escherichia coli (UPEC) strains with Multidrug-resistant (MDR) and Extensively Drug-resistant (XDR) profiles that complicate therapy for urinary tract infections (UTIs) has been observed and has directly impacted costs and extended hospital stays. The aim of this study was to determine MDR- and XDR-UPEC clinical strains, their virulence genes, their phylogenetic groups and to ascertain their relationship with integrons and genetic diversity. From a collection of 500 UPEC strains, 103 were selected with MDR and XDR characteristics. MDR-UPEC strains were mainly associated with phylogenetic groups D (54.87%) and B2 (39.02%) with a high percentage (≥70%) of several fimbrial genes ( ecpA, fimH, csgA , and papG II), an iron uptake gene ( chuA ), and a toxin gene ( hlyA ). In addition, a moderate frequency (40-70%) of other genes ( iutD, tosA , and bcs A) was observed. XDR-UPEC strains were predominantly associated with phylogenetic groups B2 (47.61%) and D (42.85%), which grouped with ≥80 virulence genes, including ecpA, fimH, csgA, papG II, iutD , and chuA . A moderate frequency (40-70%) of the tosA and hlyA genes was observed. The class 1 and 2 integrons that were identified in the MDR- and XDR-UPEC strains were associated with phylogenetic groups D, B2, and A, while the XDR-UPEC strains that were associated with phylogenetic groups B2, D, and A showed an extended-spectrum beta-lactamase (ESBL) phenotype. The modifying enzymes ( aad A1, aad B, aac C, ant 1, dfr A1, dfr A17, and aad A4) that were identified in the variable region of class 1 and 2 integrons from the MDR strains showed resistance to gentamycin (56.25 and 66.66%, respectively) and trimethoprim-sulfamethoxazole (84.61 and 66.66%, respectively). The MDR- and XDR-UPEC strains were distributed into seven clusters and were closely related to phylogenic groups B2 and D. The diversity analysis by PFGE showed 42.68% of clones of MDR-UPEC and no clonal association in the XDR-UPEC strains. In conclusion, phylogenetic groups including virulence genes are widely associated with two integron classes (1 and 2) in MDR- and XDR-UPEC strains.

Unlabelled: Staphylococcus aureus is an opportunistic pathogen that colonizes human hosts and causes a wide variety of diseases. Two interacting regulatory systems called agr (accessory gene regulator) and sar (staphylococcal accessory regulator) are involved in the regulation of virulence factors. The aim of this study was to evaluate the effect of vancomycin on hld and spa gene expression during the exponential and post-exponential growth phases in multidrug-resistant (MDR) S. aureus., Methods: Antibiotic susceptibility was evaluated by the standard microdilution method. The phylogenetic profile was obtained by pulsed-field gel electrophoresis (PFGE). Polymorphisms of agr and SCCmec (staphylococcal cassette chromosome mec) were analyzed by multiplex polymerase chain reaction (PCR). The expression levels of hld and spa were analyzed by reverse transcription-PCR. An enzyme-linked immunosorbent assay (ELISA) was performed to detect protein A, and biofilm formation was analyzed via crystal violet staining., Results: In total, 60.60% (20/33) of S. aureus clinical isolates were MDR. Half (10/20) of the MDR S. aureus isolates were distributed in subcluster 10, with >90% similarity among them. In the isolates of this subcluster, a high prevalence (100%) for the agrII and the cassette SCCmec II polymorphisms was found. Our data showed significant increases in hld expression during the post-exponential phase in the presence and absence of vancomycin. Significant increases in spa expression, protein A production and biofilm formation were observed during the post-exponential phase when the MDR S. aureus isolates were challenged with vancomycin., Conclusion: The polymorphism agrII, which is associated with nosocomial isolates, was the most prevalent polymorphism in MDR S. aureus. Additionally, under our study conditions, vancomycin modified hld and spa expression in these clinical isolates. Therefore, vancomycin may regulate alternative systems that jointly participate in the regulation of these virulence factors.

Methicillin-resistant Staphylococcus aureus (MRSA) is an important opportunistic pathogen that causes both healthcare- and community-acquired infections. An increase in the incidence of these infections may lead to a substantial change in the rate of vancomycin usage. Incidence of reduced susceptibility to vancomycin has been increasing worldwide for the last few years, conferring different levels of resistance to vancomycin as well as producing changes in the cell wall structure. The aim of the present study was to determine the effect of vancomycin on cell wall thickening in clinical isolates of vancomycin-tolerant (VT) MRSA obtained from pediatric patients. From a collection of 100 MRSA clinical isolates from pediatric patients, 12% (12/100) were characterized as VT-MRSA, and from them, 41.66% (5/12) exhibited the heterogeneous vancomycin-intermediate S. aureus (hVISA) phenotype. Multiplex-PCR assays revealed 66.66% (8/12), 25% (3/12), and 8.33% (1/12) of the VT-MRSA isolates were associated with agr group II, I, and III polymorphisms, respectively; the II-mec gene was amplified from 83.3% (10/12) of the isolates, and the mecIVa gene was amplified from 16.66% (2/12) of the isolates. Pulsed field electrophoresis (PFGE) fingerprint analysis showed 62% similarity among the VT-MRSA isolates. Thin transverse sections analyzed by transmission electron microscopy (TEM) revealed an average increase of 24 nm (105.55%) in the cell wall thickness of VT-MRSA compared with untreated VT-MRSA isolates. In summary, these data revealed that the thickened cell walls of VT-MRSA clinical isolates with agr type II and SCCmec group II polymorphisms are associated with an adaptive resistance to vancomycin.

Background: Pseudomonas aeruginosa is an opportunistic pathogen that has acquired several mechanisms of resistance to multiple groups of antibiotic agents and has been widely employed as a model organism for the study of biofilm formation. Many P. aeruginosa structures embedded in the extracellular matrix, such as exopolysaccharides (EPS), flagella, and type-IV pili (T4P), have been associated with biofilm formation. In this study, we assess biofilm formation by crystal violet quantification in clinical strains of multidrug-resistant (MDR) P. aeruginosa isolated from the Hospital Infantil de México Federico Gómez (HIMFG) associated to total and reducing EPS production (quantification by the anthrone and DNS method, respectively), twitching motility activity by T4P, and flagellar-mediated motility., Results: The determination of Minimum Inhibitory Concentration (MIC) showed that >50% of P. aeruginosa strains were resistant to 12 different antibiotics (TIC, CAZ, CTX, CRO, FEP, AZT, GM, CIP, LEV, PZT, IMP, and MEM). Total and reducing EPS analysis of the 58 biofilm-forming MDR P. aeruginosa strains showed heterogeneous values ranging from OD600 9.06 to 212.33, displaying a linear correlation with the production of total EPS (59.66μg/ml to 6000.33μg/ml; R(2)=0.89), and a higher correlation with reducing EPS (88.33μg/ml to 1100.66μg/ml; R(2)=0.96). T4P twitching motility showed a moderated linear correlation (2.00mm to 28.33mm; R(2)=0.74). Even though it has been demonstrated that flagella contribute to the initial stages of biofilm formation, crystal violet analysis showed a moderate correlation (R(2)=0.49) with flagellar-mediated motility in MDR P. aeruginosa under the tested conditions. In addition, PFGE profiles revealed two subgroups generating profiles group A, consisting of 89.63% (52/58) of the strains, and group B, consisting of 13.09% (6/58) of the strains., Conclusions: Phenotypic analysis showed a correlation among the biofilms developed in the MDR P. aeruginosa strains with EPS (total and reducing) production, T4P-activity by twitching motility and flagellar-mediated motility., (Copyright © 2014 Elsevier GmbH. All rights reserved.)