Endoscopic Retrograde Cholangiopancreatography Under General Anesthesia Compared to Conscious Sedation Study.

Background: Endoscopic retrograde cholangiopancreatography (ERCP) is used to diagnose and treat pancreatic and biliary disease. The current standard is to conduct ERCP under conscious sedation (CS). Patient movement and agitation during ERCP under CS can result in procedure failure and complications. Aiming to reduce procedure failure rates and complications, Kelowna General Hospital (KGH) in British Columbia, Canada transitioned to performing ERCP under general anesthesia (GA) as the practice standard. Objective: To determine if conducting ERCP under GA compared to CS decreases procedure complications, particularly post-ERCP pancreatitis (PEP). Methods: The charts of 2,198 patients who underwent ERCP at KGH between 2015 and 2020 were reviewed. Before September 17, 2017, ERCP was performed under CS (n = 1,316). Afterwards, ERCP was conducted under GA (n = 882). Demographic, clinical, and procedural data were extracted. The data were analyzed using univariate and multivariate statistical analysis. Results: Procedure failure rates (CS = 9 percent, GA = 3 percent, P < 0.001) decreased in the GA cohort after adjusting for age, sex, and co-morbidities. Thirty-day mortality, intensive care unit (ICU) transfer, returns post-discharge, PEP, and cholangitis rates were similar between cohorts. Conclusion: Performing ERCP under GA compared to CS resulted in an increase in procedural success rates. Other complication rates were similar between groups.

Differential protein phosphorylation is responsible for hypoxia-induced regulation of the Akt/mTOR pathway in naked mole rats.

Naked mole rats (NMRs, Heterocephalus glaber) are among the most hypoxia-tolerant mammals known. They can reduce their metabolic rate (>85%) under severe hypoxia, remain moderately active and recover with no obvious signs of damage. Hence, NMRs are an excellent model for studying mammalian hypoxia tolerance. The current study characterized the involvement of posttranslational modifications in regulating the Akt/mTOR pathway that regulates protein synthesis, and the responses of key ribosomal proteins in order to assess tissue-specific responses to 4 h exposure to 7% O2 (compared to controls at 21% O2). Results showed a tissue-specific regulation of the Akt/mTOR pathway via differential phosphorylation. Relative amounts of p-TSC(S939) in brain and of p-TSC(S939), p-Akt(473) and p-PTEN(S380) in liver increased under hypoxia, whereas levels of IGF1R(Y1135/1136) in liver decreased. In skeletal muscle, levels of p-Akt(S473) and p-PTEN(S380) decreased during hypoxia, whereas lungs showed an increase in p-mTOR(S2884) content but a decrease in p-RPS6(S235-236) under the same conditions. Analysis of the phosphorylation states of ribosomal proteins revealed increases in p-4E-BP1(T37/46) content in brain and lungs under hypoxia, as well as a rise in total 4E-BP1 protein level in liver. Phosphorylated eIF-4B(S422) content also increased in liver while levels of p-eIF-2α(S51), and eIF-4E(S209) decreased during hypoxia in liver. Overall, hypoxia altered the Akt/mTOR pathway, which correlated with a general decrease in activity of the ribosomal protein biosynthesis machinery in muscle, lung, and brain of NMRs. However, the increase in eIF-4B in liver suggests the potential promotion of cap-independent mRNA translation mechanism operating under hypoxic stress.

Naked mole rats activate neuroprotective proteins during hypoxia.

Naked mole rats are a long-lived animal model that age much like humans, but that can also withstand oxidative damage, cancer, neurodegenerative diseases, and severe hypoxic conditions, which is of particular interest to this study. The conditions of their underground burrows result in competition for oxygen consumption, yet despite this oxygen deprivation they emerge unscathed. To understand the mechanisms in place to facilitate neuronal preservation during hypoxia, we investigated the protein levels of well-known cell-stress factors. We found that under hypoxic conditions, nearly half of the proteins measured increased expression in brain, while only a few decreased. Under hypoxic conditions there appeared to be a HIF1α-centered response, where HIF1α and its interactors carbonic anhydrase 9, CITED2, p21/CIP1, and NFκB1, among others, were upregulated. Concurrently, a hypoxia-induced decrease of cytochrome c was consistent with decreased mitochondrial function and protection from apoptosis. The picture that emerges is one of neuroprotection, cell-cycle arrest, and the promotion of antiapoptotic functions, all of which are consistent with conserving energy and maintaining neural integrity under low oxygen levels. These results suggest how this species may be poised to face hypoxia and contribute to its remarkable ability to deal with myriad of other damaging factors and sets the stage for future work on the neuroprotective facilitators we identified.