Doxorubicin (DOX) is a commonly used life-saving antineoplastic agent that also causes dose-dependent cardiotoxicity. Because ATP is absolutely required to sustain normal cardiac contractile function and because impaired ATP synthesis through creatine kinase (CK), the primary myocardial energy reserve reaction, may contribute to contractile dysfunction in heart failure, we hypothesized that impaired CK energy metabolism contributes to DOX-induced cardiotoxicity. We therefore overexpressed the myofibrillar isoform of CK (CK-M) in the heart and determined the energetic, contractile and survival effects of CK-M following weekly DOX (5mg/kg) administration using in vivo 31P MRS and 1H MRI. In control animals, in vivo cardiac energetics were reduced at 7 weeks of DOX protocol and this was followed by a mild but significant reduction in left ventricular ejection fraction (EF) at 8 weeks of DOX, as compared to baseline. At baseline, CK-M overexpression (CK-M-OE) increased rates of ATP synthesis through cardiac CK (CK flux) but did not affect contractile function. Following DOX however, CK-M-OE hearts had better preservation of creatine phosphate and higher CK flux and higher EF as compared to control DOX hearts. Survival after DOX administration was significantly better in CK-M-OE than in control animals (p<0.02). Thus CK-M-OE attenuates the early decline in myocardial high-energy phosphates and contractile function caused by chronic DOX administration and increases survival. These findings suggest that CK impairment plays an energetic and functional role in this DOX-cardiotoxicity model and suggests that metabolic strategies, particularly those targeting CK, offer an appealing new strategy for limiting DOX-associated cardiotoxicity.

Background Despite a paucity of evidence to support a multitude of educational innovations, curricular leaders are pressured to find innovative solutions to better prepare medical students for an evolving twenty-first century health care system. As part of this effort, this study directly compared student-rated effectiveness scores of six different learning modalities. Methods Study participants included 286 medical students enrolled in the second-year rheumatology core at a single academic medical center between 2013 and 2017. Students were surveyed at the end of the core with a 15-item questionnaire, and student perceived effectiveness of six different learning modalities were compared. Results The modality that outperformed all others was Live Patient Encounters (LPE), with significantly higher student-rated effectiveness scores when compared to the referent modality of Problem-Based Learning (PBL). Using a 5-point Likert scale with responses ranging from “not effective” to “highly effective,” LPE received a mean effectiveness score of 4.77 followed by Augenblick (4.21), PBL (4.11), Gout Racer video game (3.49), Rheumatology Remedy e-module (3.49), and simulation knee injection (3.09). Conclusions Technologically advanced novel learning strategies were outperformed in this study by the more traditional active learning modality of LPE. This finding highlights the importance of testing innovative learning strategies at the level of the learner. Three additional conclusions can be drawn from this result. First, conflation of technology with innovation may lead to a myopic view of educational reform. Second, human factors seem to be responsible for the success of LPE and may have far-reaching educational rewards. Third, further applications of LPE should be tested in non-rheumatologic curricula. The relevance of this study is innately tied to the humanities-based application. While a formal qualitative analysis was not performed in this study, preliminary results suggest that live, structured patient interactions in the pre-clinical years of medical education may not only promote the learning of important educational objectives but also foster professional development, empathy, reflection, leadership, agency, and interpersonal skills. This “win-win” scenario (if true) would stand out as a rarity among strategic educational initiatives.

Introduction Dedicated perioperative care can be cost-effective and improve patient outcomes. Training future physicians to practice perioperative medicine is an important responsibility of medical educators. An e-learning module delivered asynchronously during clinical rotations in perioperative medicine may help to better satisfy this responsibility. Method Articulate software was used to create an interactive, 1-hour e-module based on six educational objectives. The e-module was offered as an elective self-directed learning experience to trainees on perioperative medicine clinical rotations, including third- and fourth-year medical students as well as residents from internal medicine, anesthesiology, neurology, and physical medicine and rehabilitation training programs. We assessed the effectiveness of this learning strategy as a complement to real-time clinical experiences by measuring the knowledge, confidence, and satisfaction of trainees before and after completion of the e-module. Results Of 113 trainees invited to participate, 75 completed the module and were included in our analysis. Knowledge scores improved for student ( p < .001), intern ( p < .001), and resident ( p < .001) subgroups. Confidence ratings also improved for student ( p < .001), intern ( p < .001), and resident ( p < .001) subgroups. Trainees reported high satisfaction with the e-module, and 60 (87%) reported that it would alter their practice. Discussion An e-module presenting evidence-based, interactive education to trainees during clinical rotations in perioperative medicine was an effective learning strategy. Sharing e-learning tools across institutions may help to deliver standardized education on core clinical topics, including perioperative medicine.