Propionic acidemia (PA) and methylmalonic acidemia (MMA) comprise the most common organic acidemias and account for profound morbidity in affected individuals. Although liver transplantation (LT) has emerged as a bulk enzyme-replacement strategy to stabilize metabolically fragile patients, it is not a metabolic cure because patients remain at risk for disease-related complications. We retrospectively studied LT and/or liver-kidney transplant in 9 patients with PA or MMA with additional focus on the optimization of metabolic control and management in the perioperative period. Metabolic crises were common before transplant. By implementing a strategy of carbohydrate minimization with gradual but early lipid and protein introduction, lactate levels significantly improved over the perioperative period (P < 0.001). Posttransplant metabolic improvement is demonstrated by improvements in serum glycine levels (for PA; P < 0.001 × 10 ), methylmalonic acid levels (for MMA; P < 0.001), and ammonia levels (for PA and MMA; P < 0.001). Dietary restriction remained after transplant. However, no further metabolic crises have occurred. Other disease-specific comorbidities such as renal dysfunction and cardiomyopathy stabilized and improved. In conclusion, transplant can provide a strategy for altering the natural history of PA and MMA providing stability to a rare but metabolically brittle population. Nutritional management is critical to optimize patient outcomes.

Objective.Simulation-based medical education may aid to standardize clinical performance measures, though there is little evidence for using an immersive, mannequin-based simulation for knowledge acquisition. We predicted that residents who had participated in an immersive simulation exercise illustrating the use of a clinical decision rule plus routine instructional methods (experimental group) would understand and implement this tool better than interns who participated in an immersive simulation focused on traumatic brain injury with intracranial hypertension plus routine instructional methods (control group 1). We further predicted that interns in the experimental group would understand and implement this tool as well as senior residents with more clinical experience (control group 2). Methods. This was a single center, prospective, simulation-based, randomized controlled trial. Pediatric interns were randomly assigned to clinically integrated teaching, plus a single, immersive simulation and structured debrief aimed at teaching this tool in minor head trauma (intervention), or clinically integrated teaching plus a related simulation on intracranial hypertension. Senior residents were used as an historical control arm and did not participate in a simulated encounter. Results. 20 interns (ten per group) participated in the study. Senior residents (n=40) served as historical comparisons. Interns in the intervention group scored similar to senior residents on a structured clinical observation score (median 64% vs. 57%), and better than interns in the placebo group (median 64% vs. 43%). Conclusions. In this study, a single immersive simulation improved resident learning and application of a clinical prediction rule when compared to standard resident education.

Background: MUC1-glycoprotein is expressed at low levels and in fully glycosylated form on epithelial cells. Inflammation causes MUC1 overexpression and hypoglycosylation. We hypothesized that overexpression of hypoglycosylated MUC1 would be found in postoperative Crohn’s disease (CD) recurrence and could be considered an additional biomarker of recurrence severity. Methods: We examined archived neo-terminal ileum biopsies from patients with prior ileocecal resection who had postoperative endoscopic assessment of CD recurrence and given a Rutgeerts ileal recurrence score. Consecutive tissue sections were stained using 2 different anti-MUC1 antibodies, HMPV that recognizes all forms of MUC1 and 4H5 that recognizes only inflammation-associated hypoglycosylated MUC1. Results: A total of 71 postoperative CD patients were evaluated. There was significant increase in MUC1 expression of both glycosylated/normal (P<0.0001) and hypoglycosylated/abnormal (P<0.0001) forms in patients with severe endoscopic CD recurrence (i3+i4), ileal score i2, compared with patients in endoscopic remission (i0+i1). Results were similar regardless of anti-TNF-α use. Although MUC1 expression and Rutgeerts scores were in agreement when characterizing the majority of cases, there were a few exceptions where MUC1 expression was characteristic of more severe recurrence than implied by Rutgeerts score. Conclusions: MUC1 is overexpressed and hypoglycosylated in neo-terminal ileum tissue of patients with postoperative CD recurrence. Increased levels are associated with more severe endoscopic recurrence scores, and this is not influenced by anti-TNF-α use. Discrepancies found between Rutgeerts scores and MUC1 expression suggest that addition of MUC1 as a biomarker of severity of postoperative CD recurrence may improve categorization of recurrence status and consequently treatment decisions.

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