Teaching Radiology to Medical Students in Canada; a Virtual, Integrative, Clinical Approach.

PURPOSE: To construct, apply, and evaluate a multidisciplinary approach in teaching radiology to Canadian medical students. METHODS: A multidisciplinary team of radiology and other disciplines experts designed an online 5-session course that was delivered to medical students. The topics of each session were clinical cases involving different systems. The target audience was medical students of Canadian schools. Pretests and post-tests were administered before and after each session respectively. An evaluation survey was distributed at the end of the course to gauge students' perceptions of this experience. RESULTS: An average of 425 medical students attended the live sessions. For each session, 405 students completed both the pre-tests and post-tests. In general, students scored an average of 56% higher on the post-test than on the pre-test. The final course survey was completed by 469 students. The survey results show that more than 98% of students found the course to meet or exceed their expectations. Over 80% of students agreed that the course increased their interest in radiology and about 81% agree that the topics presented were excellent and clinically important. The ratings in the final survey results also indicate that students increased their confidence in basic radiology skills after completing the course. CONCLUSIONS: The implementation of an integrative clinical approach to teaching radiology in a virtual setting is achievable. It provides efficient use of educational resources while being accessible by a large number of students across different medical schools.

Regional Elevation of Liver T1 in Fontan Patients.

Background: Fontan-associated liver disease (FALD) is characterized by hepatic congestion and progressive hepatic fibrosis in patients with the Fontan operation. This condition is generally clinically silent until late, necessitating techniques for early detection. Liver T1 mapping has been used to screen for FALD, but without consideration of regional variations in T1 values. Methods: Liver T1 measured with a liver-specific T1 mapping sequence (PROFIT1) in Fontan patients was compared with cohorts of patients with biventricular congenital heart disease (BiV-CHD) and controls with normal cardiac function and anatomy. Results: Liver T1 was significantly elevated in the Fontan cohort (n = 20) compared with patients with BiV-CHD (n = 12) and controls (n = 9) (781, 678, and 675 milliseconds, respectively; P < 0.001), with a consistent pattern of significantly elevated T1 values in the peripheral compared with central liver regions (ΔT1 = 54, 2, and 11 milliseconds; P < 0.001). PROFIT1 also yielded simultaneous T2∗ maps and fat fraction values that were similar in all groups. Fontan liver T1 values were also significantly elevated as compared with BiV-CHD and controls as measured with the cardiac (modified Look-Locker inversion) acquisitions (728, 583, and 583 milliseconds, respectively; P < 0.001) and values correlated with PROFIT1 liver T1 (R = 0.87, P < 0.001). Conclusions: Fontan patients have globally increased liver T1 values and consistent spatial variations, with higher values in the peripheral liver regions as compared with spatially uniform values in BiV-CHD and controls. The spatial patterns may provide insight into the progression of FALD. Liver T1 mapping studies should include uniform spatial coverage to avoid bias based on slice locations in this population.

Contexte: L'hépatopathie associée à une intervention de Fontan (FALD, pour Fontan-associated liver disease) se caractérise par une congestion hépatique et une fibrose hépatique évolutive chez les patients qui ont subi une intervention de Fontan. Il s'agit d'un état pathologique silencieux en début de progression, pour lequel des techniques de détection précoce sont requises. La cartographie T1 du foie est utilisée pour le dépistage de la FALD, mais sans que les variations locales des valeurs obtenues soient prises en compte. Méthodologie: Des valeurs T1 hépatiques ont été mesurées avec une séquence cartographique conçue pour le foie (PROFIT1) chez des patients qui ont subi une intervention de Fontan. Ces valeurs ont été comparées à celles d'une cohorte de patients atteints de cardiopathie congénitale biventriculaire (CC-BiV) et à celles de témoins dont l'anatomie et la fonction cardiaques étaient normales. Résultats: Les valeurs T1 hépatiques étaient significativement plus élevées chez les patients ayant subi une intervention de Fontan (n = 20) que chez les patients atteints de CC-BiV (n = 12) et chez les témoins (n = 9) (781 ms, 678 ms, 675 ms, p < 0,001), et ces valeurs tendaient à être plus élevées dans les régions périphériques que dans les régions centrales du foie (ΔT1 = 54 ms, 2 ms, 11 ms, p < 0,001). La séquence PROFIT1 a aussi permis l'obtention des valeurs de cartographie T2∗ et de teneur en matières grasses dans le foie, et ces valeurs étaient comparables pour tous les groupes. L'utilisation d'une séquence cardiaque (MOLLI, pour modified Lock-Locker inversion) a également engendré des valeurs T1 hépatiques significativement plus élevées chez les patients ayant subi l'intervention de Fontan que chez les patients atteints de CC-BiV et les témoins (728 ms, 583 ms, 583 ms, p < 0,001). Ces valeurs étaient par ailleurs corrélées avec les valeurs T1 hépatiques obtenues par la séquence PROFIT1 (R = 0,87, p < 0,001). Conclusions: Dans l'ensemble, les patients ayant subi l'intervention de Fontan présentaient des valeurs T1 hépatiques élevées accompagnées de variations spatiales. Les valeurs périphériques étaient systématiquement plus élevées, tandis que celles obtenues chez les patients atteints de CC-BiV et chez les témoins étaient uniformes. Les tendances qui sous-tendent ces variations spatiales pourraient fournir des pistes pour mieux comprendre la progression de la FALD. Enfin, les études de cartographie T1 hépatiques dans cette population devraient couvrir uniformément le foie pour éviter les biais liés à la coupe.

A Multipronged Unbiased Strategy Guides the Development of an Anti-EGFR/EPHA2-Bispecific Antibody for Combination Cancer Therapy.

PURPOSE: Accumulating analyses of pro-oncogenic molecular mechanisms triggered a rapid development of targeted cancer therapies. Although many of these treatments produce impressive initial responses, eventual resistance onset is practically unavoidable. One of the main approaches for preventing this refractory condition relies on the implementation of combination therapies. This includes dual-specificity reagents that affect both of their targets with a high level of selectivity. Unfortunately, selection of target combinations for these treatments is often confounded by limitations in our understanding of tumor biology. Here, we describe and validate a multipronged unbiased strategy for predicting optimal co-targets for bispecific therapeutics. EXPERIMENTAL DESIGN: Our strategy integrates ex vivo genome-wide loss-of-function screening, BioID interactome profiling, and gene expression analysis of patient data to identify the best fit co-targets. Final validation of selected target combinations is done in tumorsphere cultures and xenograft models. RESULTS: Integration of our experimental approaches unambiguously pointed toward EGFR and EPHA2 tyrosine kinase receptors as molecules of choice for co-targeting in multiple tumor types. Following this lead, we generated a human bispecific anti-EGFR/EPHA2 antibody that, as predicted, very effectively suppresses tumor growth compared with its prototype anti-EGFR therapeutic antibody, cetuximab. CONCLUSIONS: Our work not only presents a new bispecific antibody with a high potential for being developed into clinically relevant biologics, but more importantly, successfully validates a novel unbiased strategy for selecting biologically optimal target combinations. This is of a significant translational relevance, as such multifaceted unbiased approaches are likely to augment the development of effective combination therapies for cancer treatment. See related commentary by Kumar, p. 2570.