RESUMO
Audience: This simulation case was created for emergency medicine (EM) residents at all levels of training. Background: Cardiac electrical storm (ES) is commonly defined as three or more episodes of sustained ventricular tachycardia, ventricular fibrillation, or three shocks from an implantable defibrillator within a 24 hour period.1 This can occur in up to 30-40% of patients with implantable defibrillators; however, it may also present in a wide variety of patients, including those with structural heart disease, myocardial infarction, electrolyte disturbances, and channelopathies.2,3 With each subsequent episode of ventricular arrhythmia, the arrhythmogenic potential of the heart may increase secondary to increased intracellular calcium dysregulation, myocardial injury, and increased endogenous release of catecholamines. The increased pain and catecholamine release from cardioversion/defibrillation and exogenous epinephrine during cardiac arrest further exacerbates ES.2 This carries a significant mortality risk of up to 12% in the first 48 hours.3This case involves a basic knowledge of the Advanced Cardiac Life Support (ACLS) for ventricular tachycardia, both with and without a pulse, and the application of Sgarbossa criteria in a patient with an ST elevation myocardial infarction (STEMI) which makes it ideal for the PGY-1. However, the case quickly becomes refractory to the basic management prescribed in ACLS, requiring trouble shooting and quick thinking about deeper pathophysiology, a skill that is crucial for all emergency medicine physicians. There are multiple ways to troubleshoot this case, making for a good variety of discussion and recent literature review on the complexities of a relatively common arrhythmia, ventricular tachycardia. Educational Objectives: By the end of this simulation, learners should be able to: 1) recognize unstable ventricular tachycardia and initiate ACLS protocol, 2) practice dynamic decision making by switching between various ACLS algorithms, 3) create a thoughtful approach for further management of refractory ventricular tachycardia, 4) interpret electrocardiogram (ECG) with ST-segment elevation (STE) and left bundle branch block (LBBB), 5) appropriately disposition the patient and provide care after return of spontaneous circulation (ROSC), 6) navigate a difficult conversation with the patient's husband when she reveals that the patient's wishes were to not be resuscitated. Educational Methods: This simulation was performed using high-fidelity simulation followed by an immediate debriefing with nine learners who directly participated in the SIM and twenty-three residents, who were online observers via Zoom. This case was done during our conference day, and there were a total of approximately forty total learners comprised of medical students, PGY-1, PGY-2 and PGY-3 residents. There were several medical students who also observed via Zoom but were not surveyed, and the survey was sent to 32 learners. The case was run three separate times with each session consisting of three-four learners at the same level of training, with other learners in the same level of training observing via Zoom™ video platform. Since we can only have a team of three-four learners participate per group during simulation, the rest of the learners were observing the case and the debrief. There was one simulation instructor and one technician. Research Methods: We sent an online survey to all the participants and the observers after the debrief via surveymonkey.com. The survey collected responses to the following statements: (1) the case was believable, (2) the case had right amount of complexity, (3) the case helped in improving medical knowledge and patient care, (4) the simulation environment gave me a real-life experience and, (5) the debriefing session after simulation helped improve my knowledge. Likert scale was used to collect the responses. Results: A total of thirteen participants responded to the survey. One hundred percent of them either strongly agreed or agreed that the case was believable and that it helped in improving medical knowledge and patient care. Fifty-four percent strongly agreed, 38 percent agreed, and eight percent were neutral about the case having the right amount of complexity. Thirty one percent strongly agreed, 61 percent agreed, and eight percent were neutral about the case giving them real-life experience. All of them agreed that the debriefing session helped them improve their knowledge. Discussion: The high-fidelity simulation case was helpful with educating learners with ventricular tachycardia and fibrillation. Learners learned how to switch between various ACLS algorithms and how to manage a patient with refractory ventricular fibrillation. Learners enforced their knowledge in how to communicate with patient's family members when the patient does not want resuscitation. Topics: Stable ventricular tachycardia, unstable ventricular tachycardia, refractory ventricular tachycardia, electrical storm, STEMI equivalents, medical simulation.
RESUMO
Duchenne muscular dystrophy (DMD) is a fatal muscle disease caused by mutations in the dystrophin gene, resulting in a complete loss of the dystrophin protein. Dystrophin is a critical component of the dystrophin glycoprotein complex (DGC), which links laminin in the extracellular matrix to the actin cytoskeleton within myofibers and provides resistance to shear stresses during muscle activity. Loss of dystrophin in DMD patients results in a fragile sarcolemma prone to contraction-induced muscle damage. The α7ß1 integrin is a laminin receptor protein complex in skeletal and cardiac muscle and a major modifier of disease progression in DMD. In a muscle cell-based screen for α7 integrin transcriptional enhancers, we identified a small molecule, SU9516, that promoted increased α7ß1 integrin expression. Here we show that SU9516 leads to increased α7B integrin in murine C2C12 and human DMD patient myogenic cell lines. Oral administration of SU9516 in the mdx mouse model of DMD increased α7ß1 integrin in skeletal muscle, ameliorated pathology, and improved muscle function. We show that these improvements are mediated through SU9516 inhibitory actions on the p65-NF-κB pro-inflammatory and Ste20-related proline alanine rich kinase (SPAK)/OSR1 signaling pathways. This study identifies a first in-class α7 integrin-enhancing small-molecule compound with potential for the treatment of DMD.
