Outcomes in patients with pancreatic ductal adenocarcinoma (PDAC) undergoing robotic (RPD) or open pancreaticoduodenectomies (OPD): a propensity score-weighted survival analysis.

The purpose of this study was to compare the survival, recurrence, and complication rates in patients with pancreatic ductal adenocarcinoma (PDAC) who underwent robotic pancreaticoduodenectomy (RPD) or open pancreaticoduodenectomy (OPD) and who received adjuvant therapy. The study was a single-center retrospective analysis of consecutive PDAC patients who underwent RPD/OPD. Patient characteristics, tumor findings, neoadjuvant therapy, adjuvant therapies, overall survival (OS) and recurrence-free survival (RFS) were compared between the OPD and RPD cohorts. Cox proportional hazard regression with and without propensity score matching was used to establish the association between predictors and outcomes. One hundred PDAC patients underwent OPD (n = 36) or RPD (n = 64) from 2013 to 2019. Cox proportional hazard models showed that baseline bilirubin (HR 1.6, p = 0.0006) and operative characteristics such as the number of positive lymph nodes (HR 1.1, p = 0.002), lymph node ratio (HR 1.6, p = 0.001), tumor grade (HR 1.7, p = 0.02), and TNM classification (HR 2.3, p = 0.01) were associated with OS. The independent predictors post-intervention associated with mortality were adjuvant therapy (HR 0.4, p = 0.0003), ISGPS complications (HR 2.8, p = 0.02), and 90-day readmission (HR 2, p = 0.004). After adjustment for these predictors, adjuvant therapy, baseline bilirubin, lymph node ratio, and tumor grade remained the main predictors of mortality. Baseline bilirubin, adjuvant therapy, lymph node ratio, and tumor grade were the main determinants of mortality after OPD or RPD. There was no significant difference in OS and RFS after RPD or OPD in PC patients who received adjuvant therapy.

An extract of Artemisia dracunculus L. inhibits ubiquitin-proteasome activity and preserves skeletal muscle mass in a murine model of diabetes.

Impaired insulin signaling is a key feature of type 2 diabetes and is associated with increased ubiquitin-proteasome-dependent protein degradation in skeletal muscle. An extract of Artemisia dracunculus L. (termed PMI5011) improves insulin action by increasing insulin signaling in skeletal muscle. We sought to determine if the effect of PMI5011 on insulin signaling extends to regulation of the ubiquitin-proteasome system. C2C12 myotubes and the KK-A(y) murine model of type 2 diabetes were used to evaluate the effect of PMI5011 on steady-state levels of ubiquitylation, proteasome activity and expression of Atrogin-1 and MuRF-1, muscle-specific ubiquitin ligases that are upregulated with impaired insulin signaling. Our results show that PMI5011 inhibits proteasome activity and steady-state ubiquitylation levels in vitro and in vivo. The effect of PMI5011 is mediated by PI3K/Akt signaling and correlates with decreased expression of Atrogin-1 and MuRF-1. Under in vitro conditions of hormonal or fatty acid-induced insulin resistance, PMI5011 improves insulin signaling and reduces Atrogin-1 and MuRF-1 protein levels. In the KK-A(y) murine model of type 2 diabetes, skeletal muscle ubiquitylation and proteasome activity is inhibited and Atrogin-1 and MuRF-1 expression is decreased by PMI5011. PMI5011-mediated changes in the ubiquitin-proteasome system in vivo correlate with increased phosphorylation of Akt and FoxO3a and increased myofiber size. The changes in Atrogin-1 and MuRF-1 expression, ubiquitin-proteasome activity and myofiber size modulated by PMI5011 in the presence of insulin resistance indicate the botanical extract PMI5011 may have therapeutic potential in the preservation of muscle mass in type 2 diabetes.