ABSTRACT
Background: Enhanced recovery programs (ERPs) improve outcomes, but over 20 % of patients fail ERP and the contribution of social vulnerability is unknown. This study aimed to characterize the association between social vulnerability and ERP adherence and failure. Methods: This was a retrospective cohort study of colorectal surgery patients between 2015 and 2020 utilizing ACS-NSQIP data. Patients who failed ERP (LOS > 6 days) were compared to patients not failing ERP. The CDC's social vulnerability index (SVI) was used to assess social vulnerability. Result: 273 of 1191 patients (22.9 %) failed ERP. SVI was a significant predictor of ERP failure (OR 4.6, 95 % CI 1.3-16.8) among those with >70 % ERP component adherence. SVI scores were significantly higher among patients non-adherent with 3 key ERP components: preoperative block (0.58 vs. 0.51, p < 0.01), early diet (0.57 vs. 0.52, p = 0.04) and early foley removal (0.55 vs. 0.50, p < 0.01). Conclusions: Higher social vulnerability was associated with non-adherence to 3 key ERP components as well as ERP failure among those who were adherent with >70 % of ERP components. Social vulnerability needs to be recognized, addressed, and included in efforts to further improve ERPs. Key message: Social vulnerability is associated with non-adherence to enhanced recovery components and ERP failure among those with high ERP adherence. Social vulnerability needs to be addressed in efforts to improve ERPs.
ABSTRACT
Duchenne muscular dystrophy, the most common form of childhood muscular dystrophy, is caused by X-linked inherited mutations in the dystrophin gene. Dystrophin deficiencies result in the loss of the dystrophin-glycoprotein complex at the plasma membrane, which leads to structural instability and muscle degeneration. Previously, we induced muscle-specific overexpression of Akt, a regulator of cellular metabolism and survival, in mdx mice at pre-necrotic (<3.5 weeks) ages and demonstrated upregulation of the utrophin-glycoprotein complex and protection against contractile-induced stress. Here, we found that delaying exogenous Akt treatment of mdx mice after the onset of peak pathology (>6 weeks) similarly increased the abundance of compensatory adhesion complexes at the extrasynaptic sarcolemma. Akt introduction after onset of pathology reverses the mdx histopathological measures, including decreases in blood serum albumin infiltration. Akt also improves muscle function in mdx mice as demonstrated through in vivo grip strength tests and in vitro contraction measurements of the extensor digitorum longus muscle. To further explore the significance of Akt in myofiber regeneration, we injured wild-type muscle with cardiotoxin and found that Akt induced a faster regenerative response relative to controls at equivalent time points. We demonstrate that Akt signaling pathways counteract mdx pathogenesis by enhancing endogenous compensatory mechanisms. These findings provide a rationale for investigating the therapeutic activation of the Akt pathway to counteract muscle wasting.
