Search

Humans with monogenic inborn errors responsible for extreme disease phenotypes can reveal essential physiological pathways. We investigated germline mutations in GNAI2 , which encodes G αi2 , a key component in heterotrimeric G protein signal transduction usually thought to regulate adenylyl cyclase-mediated cyclic adenosine monophosphate (cAMP) production. Patients with activating G αi2 mutations had clinical presentations that included impaired immunity. Mutant G αi2 impaired cell migration and augmented responses to T cell receptor (TCR) stimulation. We found that mutant G αi2 influenced TCR signaling by sequestering the guanosine triphosphatase (GTPase)-activating protein RASA2, thereby promoting RAS activation and increasing downstream extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)-AKT S6 signaling to drive cellular growth and proliferation.

Patients born with obstructed total anomalous pulmonary venous return have a high risk of morbidity and mortality in the neonatal period, which only increases when combined with single ventricle physiology and non-cardiac congenital anomalies such as heterotaxy syndrome. Despite advances in management of congenital heart disease, surgery within the first weeks of life to repair the pulmonary venous connection and establish pulmonary blood flow with a systemic-to-pulmonary shunt has historically led to disappointing outcomes. A multidisciplinary approach with pediatric interventional cardiology and cardiac surgery is required to reduce morbidity and mortality in this extremely high-risk patient population. Extending the time between birth and cardiac surgery can lessen postoperative complications and mortality risk, especially in patients with abnormal thoracoabdominal relationships. Our team was able to successfully utilize transcatheter stent placement in a vertical vein and patent ductus arteriosus to delay and stage cardiac surgeries in an infant born with obstructed total anomalous pulmonary venous return, unbalanced atrioventricular septal defect with pulmonary atresia and heterotaxy, thus reducing the morbidity and mortality associated with this diagnosis., (© 2023. The Author(s).)

Objective: Simulation education and assessment are increasingly used in prehospital curriculums. The objective of this study was to assess the challenges and feasibility of correlating evaluation data from an airway management simulation assessment with clinical performance., Methods: This study was undertaken in Ontario, the most populous province in Canada, where 13 bases are distributed in geographically diverse areas, from urban to rural and remote locations. This is a retrospective cohort study of paramedics who had completed simulation education and assessment in rapid sequence intubation. Logistic regression was used to assess for correlation between assessment scores (ie, the global score and the overall score and the definitive airway sans hypoxia/hypotension on the first attempt [DASH-1A] success in the field)., Results: DASH-1A success when grouped by base varied from 25% to 100%. The odds of DASH-1A success increased for paramedics who had a higher overall score (odds ratio [OR]: 1.03; 95% confidence interval [CI], 0.96-1.11) and for paramedics who had a higher global rating (OR: 1.27; CI, 0.73-2.21) when accounting for base intubation frequency. The odds of DASH-1A success increased for paramedics who had a higher overall score (OR: 1.01; CI, 0.93-1.09) and decreased for paramedics who had a higher global rating (OR: 0.96; CI, 0.47-1.96) when accounting for base geography., Conclusion: Although this study lacked a sample size large enough to draw conclusions, it provides a foundation and areas to improve in future work exploring the relationship between simulation assessments and clinical performance., Competing Interests: Declaration of Competing Interest The author(s) have no relevant disclosures. There was no grant funding or financial support for this manuscript., (Copyright © 2024 Air Medical Journal Associates. Published by Elsevier Inc. All rights reserved.)

Background: Outflow graft obstruction (OGO) is an uncommon yet life-threatening complication in patients with left ventricular assist devices (LVADs). In this retrospective, single-center case series, we identify the baseline demographics and presenting features of patients who develop LVAD OGO and the procedural details and outcomes surrounding percutaneous endovascular intervention (PEI)., Methods: We conducted a retrospective review of patients with LVADs at our institution between January 2010 and February 2023 who developed OGO and were treated with PEI. Details of the PEI including procedure time, fluoroscopy time, contrast use, stent size, number of stents, change in gradient, and change in flow after intervention were collected., Results: A total of 12 patients who had 14 cases of OGO were identified from January 2010 to February 2023. The average age at presentation was 64.78 years. Nine of the 14 cases occurred in male patients. Eleven of the 14 cases occurred with Heartware devices (2 recurrences), 2 in Heartmate 2 and 1 in Heartmate 3. Notable procedural details include a mean procedure time of 90.86 min and mean contrast use of 162.5 mL. The initial gradient across the OGO was reduced by an average of 72 %, to a mean post-PEI of 11.57 mmHg. The average number of stents to achieve this gradient was around 2.08, with the most common stent diameter being 10 mm. Thirty-day mortality after PEI was 7 % (1/14) in this high-risk patient population., Conclusion: In our single-center experience, PEI can be a safe and effective treatment for LVAD OGO., Competing Interests: Declaration of competing interest Toby Rogers – Consultant: Edwards Lifesciences, Medtronic, Boston Scientific; Advisory board: Medtronic, Boston Scientific; Equity: Transmural Systems; Intellectual property: co-inventor on patents, assigned to NIH. Michael Slack – Proctor: Abbott. Farooq H. Sheikh – Institutional research support: Abbott, Alnylam, Ionis, BridgeBio; Speaker fee (educational conferences): Abbott. Gaby Weissman – Director of an academic cardiac computed tomography core lab with institutional contracts with Abbott, Boston Scientific, Medtronic, and Neovasc. Ron Waksman – Advisory Board: Abbott Vascular, Boston Scientific, Medtronic, Philips IGT, Pi-Cardia Ltd.; Consultant: Abbott Vascular, Append Medical, Biotronik, Boston Scientific, JC Medical, MedAlliance/Cordis, Medtronic, Philips IGT, Pi-Cardia Ltd., Swiss Interventional/SIS Medical AG, Transmural Systems Inc.; Institutional Grant Support: Biotronik, Medtronic, Philips IGT; Investor: Append Medical, Pi-Cardia Ltd., Transmural Systems Inc. All other authors — None., (Copyright © 2024. Published by Elsevier Inc.)

Objectives: This study aims to assess the feasibility to perform transoral robotic surgery (TORS) with a new robotic platform, the Versius Surgical System (CMR Surgical, UK) in a preclinical cadaveric setting in accordance to stage 0 of the IDEAL-D framework., Design: IDEAL stage 0 preclinical assessment of the Versius Robotic System in TORS in human cadavers., Setting: All procedures were performed in a simulated operating theatre environment at a UK surgical training centre., Participants: 11 consultant head and neck surgeons from the UK, mainland Europe and the USA took part in TORS procedures on six human cadavers., Interventions: 3 key index procedures were assessed that represent the core surgical workload of TORS: lateral oropharyngectomy, tongue base resection and partial supraglottic laryngectomy., Main Outcome Measures: The primary outcome was the successful completion of each surgical procedure. Secondary outcomes included the optimisation of system setup, instrumentation and surgeon-reported outcomes for feasibility of each component procedural step., Results: 33 cadaveric procedures were performed and 32 were successfully completed. One supraglottic laryngectomy was not fully completed due to issues dividing the epiglottic cartilage with available instrumentation. Surgeon-reported outcomes met the minimal level of feasibility in all procedures and a consensus that it is feasible to perform TORS with Versius was reached. Available instrumentation was not representative of other robotic platforms used in TORS and further instrument optimisation is recommended before wider dissemination., Conclusions: It is feasible to perform TORS with the Versius Surgical System (CMR Surgical) within a pre-clinical cadaveric setting. Clinical evaluation is needed and appropriate with the system. Further instrument development and optimisation is desirable., Competing Interests: Competing interests: This study was funded by CMR Surgical Ltd. including providing access to laboratory space, cadavers and the robotic system. Mark Slack is a co-founder and current chief medical officer of CMR Surgical., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Funding Support and Author Disclosures Dr Slack has served as a proctor for Abbott. Dr Waksman has served on the advisory board for Abbott Vascular, Boston Scientific, Medtronic, Philips IGT, and Pi-Cardia Ltd; has served as a consultant for Abbott Vascular, Biotronik, Boston Scientific, Cordis, Medtronic, Philips IGT, Pi-Cardia Ltd, Swiss Interventional Systems/SIS Medical AG, Transmural Systems Inc, and Venous MedTech; has received institutional grant support from Amgen, Biotronik, Boston Scientific, Chiesi, Medtronic, and Philips IGT; and is an investor in MedAlliance and Transmural Systems. Dr Rogers has served as a proctor and consultant for Medtronic, Edwards Lifesciences, Boston Scientific, and Abbott; has served on the advisory board for Medtronic, Boston Scientific, and Abbott; and owns equity interest in Transmural Systems. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Purpose: Explore gender disparities in patients undergoing transseptal puncture (TSP) for selected transcatheter cardiac intervention procedures., Methods: Patients who underwent TSP from January 2015 through September 2021 were reviewed. Primary outcomes were procedural and in-hospital major adverse events. Secondary endpoints were procedural success and hospitalization length of stay (LOS) >1 day. Unadjusted and multivariable-adjusted logistic regression analyses were performed to assess gender differences for in-hospital adverse events., Results: The study cohort comprised 510 patients (mean [SD] age, 74 [14.0] years); 246 women (48 %) underwent TSP for left atrial appendage occlusion (LAAO) or transcatheter edge-to-edge-repair (TEER). Compared with men, women were younger, had higher CHA 2 DS 2 -VASc scores, and were more likely to have had a prior ischemic stroke, but were less likely to have paroxysmal atrial fibrillation. After multivariable adjustment, there were no differences between genders in aborted or canceled procedures (odds ratio [OR]: 0.43; 95 % confidence interval [CI]: 0.10-1.96; p = 0.277), any adverse events (OR: 1.00; 95 % CI: 0.58-1.70; p = 0.98), major adverse events (OR: 1.60; 95 % CI: 0.90-2.80; p = 0.11), or death (OR: 1.00; 95 % CI: 0.20-5.00; p = 0.31). Subgroup analysis for LAAO procedures showed that at 30 days, women had higher rates of adverse events, major adverse cardiac events, and LOS >1 day., Conclusions: Men and women showed no differences in procedural success and in-hospital adverse outcomes in unadjusted analysis and after multivariable adjustment, despite women having a higher risk profile among patients undergoing TSP. However, compared with men, women undergoing LAAO experienced a higher rate of in-hospital adverse events irrespective of TSP., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ron Waksman reports serving on the advisory boards of Abbott Vascular, Boston Scientific, Medtronic, Philips IGT, and Pi-Cardia Ltd.; being a consultant for Abbott Vascular, Biotronik, Boston Scientific, Cordis, Medtronic, Philips IGT, Pi-Cardia Ltd., Swiss Interventional Systems/SIS Medical AG, Transmural Systems Inc., and Venous MedTech; receiving institutional grant support from Amgen, Biotronik, Boston Scientific, Chiesi, Medtronic, and Philips IGT; and being an investor in MedAlliance and Transmural Systems Inc. Toby Rogers reports being a proctor and consultant for Boston Scientific, Edwards Lifesciences, and Medtronic; serving on the Advisory Board of Medtronic; being a co-inventor on patents for transcatheter electrosurgery devices, assigned to NIH; and holding equity interest in Transmural Systems Inc. All other authors have no conflicts to disclose., (Copyright © 2023. Published by Elsevier Inc.)

Introduction: A climate survey was piloted to obtain an understanding of the perceptions and personal experiences of faculty for intentional planning of future meaningful, effective, and sustainable diversity, equity, and inclusion (DEI) efforts at a college of pharmacy., Methods: A 48-item, four section, online survey was developed and administered to 69 faculty between October and November 2021. Likert-like five-point scales and free-text items were included to determine an overall assessment of climate, as well as perceptions and/or personal experiences for each domain of DEI, and demographics., Results: Thirty-nine (57%) faculty completed the survey. For climate, every attribute had at least one respondent that observed someone make an insensitive or disparaging remark "rarely," "occasionally," and "frequently." The response pattern was similar for personal experience with insensitive remarks. For participation in diversity activities, "awareness without participation" was selected by 56% of respondents. For perceptions of diversity, "fairly" or "very" was selected by 38% to 54% of respondents. For equity, "attainable for some" to "not attainable" was identified for 15% to 26% of respondents., Conclusions: These pilot climate survey results inform climate improvement as it relates to DEI and informs survey instrument refinement., Competing Interests: Conflict of interest None., (Copyright © 2023. Published by Elsevier Inc.)