Real-time mortality risk calculator following pancreatoduodenectomy: quantifying the impact of perioperative events

BackgroundEstimation of mortality risk traditionally has only included preoperative factors. We sought to develop “real-time” mortality risk-calculator for patients who undergo pancreatoduodenectomy (PD) based on preoperative factors, as well as events that occurred during the course of patient's surgery and hospitalization.MethodsPatients who underwent PD from 2014 to 2018 were identified in the ACS-NSQIP dataset. Training and validation cohorts were created. Pre-, intra-, and post-operative models to predict 30-day mortality were developed based on perioperative variables selected by stepwise cox regression analyses; model performance was assessed using AUC.ResultsAmong 17,683 patients who underwent PD, 1.6% died within 30-days. Patient factors and events associated with 30-day mortality were incorporated into a risk calculator (https://ktsahara.shinyapps.io/Real-timePD/). The accuracy of the risk-calculator increased relative to hospital time-course in both the training (AUC, pre-:0.696, intra-:0.724, post-operative:0.871) and validation (AUC, pre-:0.681, intra-:0.702, post-operative:0.850) cohorts. One in 3 patients had a concordant calculated risk of mortality using pre-versus postoperative variables to inform the risk model (kappa = 0.474).ConclusionRisk of mortality fluctuated over the hospital course following PD and preoperative risk assessment was often discordant with risk assessed at other periods. The proposed “real-time” calculator may help better stratify patients with increased risk of 30-day mortality.     

A targeted approach to phosphoinositide-3-kinase/Akt/mammalian target of rapamycin-induced hyperglycemia

Phosphoinositide-3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway inhibitors are a novel class of antineoplastic agent available for the treatment of various cancers. With improved cancer outcomes and survival, individuals are exposed to these antineoplastic therapies for longer periods of time and therefore, the consideration of adverse effects is of increasing importance. The PI3K/Akt/mTOR signaling pathway plays a critical role in regulating cellular processes such as growth and proliferation, but also regulates the metabolic effects of insulin such as glucose uptake and glycogen synthesis. Therefore, hyperglycemia and insulin resistance are frequently reported adverse effects. There are no recent consensus guidelines on the management of hyperglycemia secondary to PI3K/Akt/mTOR inhibitors, with the latest guidelines produced in 2012 – when many of these agents were still undergoing development. As we now have a greater understanding of the underlying mechanisms and patterns in which hyperglycemia is induced and access to an increasing array of glucose-lowering agents, an update of the previous guidelines accommodating these understandings and developments is timely. This review will provide a comprehensive summary of the current literature with regards to the incidence of hyperglycemia associated with each agent, as well as the different pathways and mechanisms in which hyperglycemia is induced. Our proposed up-to-date strategy for the specific management of PI3K/Akt/mTOR inhibitor-induced hyperglycemia will also aim to facilitate management of this complex oncological population.     

Treatment-refractory schizophrenia: Update on concepts and interventions

Until recently, clinicians have had little reason for enthusiasm in the treatment of a significant proportion of the population with schizophrenia. Approximately 15% of these patients are unresponsive to traditional antipsychotic therapy. Defining this severely ill, treatment-refractory group of patients can be a difficult task. Despite the complexity of the undertaking, it is important that such patients be identified so that their treatment can be optimized. There is increasing evidence that new, atypical antipsychotic agents can not only ameliorate both positive and negative symptoms of schizophrenia, but can also improve patients' vocational, social, and cognitive functioning as well as their overall quality of life. Free of the limitations imposed by conventional antipsychotics, patients are now able to effectively partake in many available treatments. Psychiatric rehabilitation now becomes an achievable reality. The advent of atypical antipsychotics has clearly shown that there is a much greater potential for recovery from schizophrenia than we had previously thought possible.