Fluoroless catheter ablation of atrial fibrillation: integration of intracardiac echocardiography and cartosound module

Objective: To evaluate the feasibility, safety, and clinical efficacy of non-fluoroscopic radiofrequency catheter ablation of atrial fibrillation (AF) in comparison to traditional fluoroscopy-guided ablation in a local Canadian community cohort. Methods: We retrospectively studied consecutive patients with paroxysmal and persistent AF undergoing pulmonary vein isolation (PVI) guided by intracardiac echocardiography (ICE) and Carto system (CartoSound module). ICE-guided PVI without fluoroscopy (Zero-fluoro group) was performed in 116 patients, and conventional fluoroscopy-guided PVI (Traditional group) was performed in 131 patients. Results: Two hundred and forty-seven patients with AF (60.7% male; mean age: 62.2 ± 10.6 years; paroxysmal AF =63.1%) who underwent PVI were studied. Mean procedure times were similar between both groups (136.8±33.4 minutes in the zero-fluoro group vs. 144.3±44.9 minutes in the traditional group; p=0.2). Acute PVI was achieved in all patients. Survival from early AF recurrence was 85% and 81% in the zero-fluoro and traditional groups, respectively (p = 0.06). Survival from late AF recurrence (12-months) between the zero-fluoro and traditional groups was also similar (p=0.1). Moreover, there were no significant differences between complication rates, including hematoma (p = 0.2) and tamponade (p = 1),between both groups. Conclusions: Zero-fluoroscopy ICE and CartoSound-guided AF ablation may be safe and feasible in patients undergoing PVI compared to conventional fluoroscopy-guided ablation

LEARN: A multi-centre, cross-sectional evaluation of Urology teaching in UK medical schools

OBJECTIVE: To evaluate the status of UK undergraduate urology teaching against the British Association of Urological Surgeons (BAUS) Undergraduate Syllabus for Urology. Secondary objectives included evaluating the type and quantity of teaching provided, the reported performance rate of General Medical Council (GMC)-mandated urological procedures, and the proportion of undergraduates considering urology as a career. MATERIALS AND METHODS: LEARN was a national multicentre cross-sectional study. Year 2 to Year 5 medical students and FY1 doctors were invited to complete a survey between 3rd October and 20th December 2020, retrospectively assessing the urology teaching received to date. Results are reported according to the Checklist for Reporting Results of Internet E-Surveys (CHERRIES). RESULTS: 7,063/8,346 (84.6%) responses from all 39 UK medical schools were included; 1,127/7,063 (16.0%) were from Foundation Year (FY) 1 doctors, who reported that the most frequently taught topics in undergraduate training were on urinary tract infection (96.5%), acute kidney injury (95.9%) and haematuria (94.4%). The most infrequently taught topics were male urinary incontinence (59.4%), male infertility (52.4%) and erectile dysfunction (43.8%). Male and female catheterisation on patients as undergraduates was performed by 92.1% and 73.0% of FY1 doctors respectively, and 16.9% had considered a career in urology. Theory based teaching was mainly prevalent in the early years of medical school, with clinical skills teaching, and clinical placements in the later years of medical school. 20.1% of FY1 doctors reported no undergraduate clinical attachment in urology. CONCLUSION: LEARN is the largest ever evaluation of undergraduate urology teaching. In the UK, teaching seemed satisfactory as evaluated by the BAUS undergraduate syllabus. However, many students report having no clinical attachments in Urology and some newly qualified doctors report never having inserted a catheter, which is a GMC mandated requirement. We recommend a greater emphasis on undergraduate clinical exposure to urology and stricter adherence to GMC mandated procedures

Characterizing and Overriding the Structural Mechanism of the Quizartinib-Resistant FLT3 “Gatekeeper” F691L Mutation with PLX3397

Tyrosine kinase domain mutations are a common cause of acquired clinical resistance to tyrosine kinase inhibitors (TKIs) used to treat cancer, including the FLT3 inhibitor quizartinib. Mutation of kinase “gatekeeper” residues, which control access to an allosteric pocket adjacent to the ATP-binding site, have been frequently implicated in TKI resistance. The molecular underpinnings of gatekeeper mutation-mediated resistance are incompletely understood. We report the first co-crystal structure of FLT3 with the TKI quizartinib, which demonstrates that quizartinib binding relies on essential edge-to-face aromatic interactions with the gatekeeper F691 residue, and F830 within the highly conserved DFG motif in the activation loop. This reliance makes quizartinib critically vulnerable to gatekeeper and activation loop substitutions while minimizing the impact of mutations elsewhere. Moreover, we identify PLX3397, a novel FLT3 inhibitor that retains activity against the F691L mutant due to a binding mode that depends less vitally on specific interactions with the gatekeeper position