Infant Botulism.

Audience: Emergency medicine and pediatric residents, and pediatric emergency medicine (PEM) fellows. Introduction: Botulism is a rare but serious cause of infant hypotonia, vomiting, and respiratory failure. The differential diagnosis and management of a hypotonic infant with progressive weakness leading to respiratory failure is a rare presentation with high morbidity and mortality.1 Infants with botulism generally present with vague complaints that progressively worsen over time.2 Recognition of descending paralysis in an infant as well as signs of respiratory failure are key to preventing an adverse outcome. A key component of botulism treatment is recognizing the need to mobilize local resources to obtain BabyBIG® (botulism immune globulin). This process can and should begin in the emergency department. Educational Objectives: After this simulation learners should be able to: 1) develop a differential diagnosis for the hypotonic infant, 2) recognize signs and symptoms of infant botulism, 3) recognize respiratory failure and secure the airway with appropriate rapid sequence intubation (RSI) medications, 4) initiate definitive treatment of infant botulism by mobilizing resources to obtain antitoxin, 5) continue supportive management and admit the patient to the pediatric intensive care unit (PICU), 6) understand the pathophysiology and epidemiology of infant botulism, 7) develop communication and leadership skills when evaluating and managing critically ill infants. Educational Methods: This simulation case was performed using a high-fidelity Laerdal SimBaby with intubating capabilities and real-time vital sign monitoring. Additionally, this case can be performed with low fidelity manikins with supplemental scripting and visual stimuli. With minor adjustments, this case could be modified into an oral boards case. Research Methods: We obtained feedback from a convenience sample of random participants after the simulation case and debrief were completed. The sample of emergency medicine residents (N=21) and PEM fellow (N=1) completed 5 questions on a 5-point Likert scale. Results: The emergency medicine residents and PEM fellow had mostly favorable feedback regarding the simulation and debriefing. Most strongly agreed or agreed that this would improve their performance in an actual clinical setting. Discussion: Infant botulism is a rare condition, presenting as vague non-specific complaints that worsen over time. It is important to differentiate infant botulism from other causes of weakness, hypotonia, and respiratory failure. This case presents learners with a high acuity, rare case of infant botulism and allows them to work through a complex pediatric patient encounter in a psychologically safe space. The presence of a standardized patient to play the patient's parent is key to assess learners' nontechnical communication skills and to increase fidelity during the simulation. Topics: Infant botulism, pediatric emergency medicine, respiratory failure, hypotonia, toxicology.

Smads as muscle biomarkers in amyotrophic lateral sclerosis.

OBJECTIVE: To identify molecular signatures in muscle from patients with amyotrophic lateral sclerosis (ALS) that could provide insight into the disease process and serve as biomarkers. METHODS: RNA sequencing was performed on ALS and control muscle samples to identify Smad family members as potential markers of disease. Validation studies were performed in a cohort of 27 ALS patients and 33 controls. The markers were assessed in the G93A superoxide dismutase (SOD)1 mouse at different stages of disease and in a model of sciatic nerve injury. RESULTS: Smad8, and to a lesser extent Smad1 and 5, mRNAs were significantly elevated in human ALS muscle samples. The markers displayed a remarkably similar pattern in the G93A SOD1 mouse model of ALS with increases detected at preclinical stages. Expression at the RNA and protein levels as well as protein activation (phosphorylation) significantly increased with disease progression in the mouse. The markers were also elevated to a lesser degree in gastrocnemius muscle following sciatic nerve injury, but then reverted to baseline during the muscle reinnervation phase. INTERPRETATION: These data indicate that Smad1, 5, 8 mRNA and protein levels, as well as Smad phosphorylation, are elevated in ALS muscle and could potentially serve as markers of disease progression or regression.