Predicting procedure duration of colorectal endoscopic submucosal dissection at Western endoscopy centers

Background and study aims Overcoming logistical obstacles for the implementation of colorectal endoscopic submucosal dissection (ESD) requires accurate prediction of procedure times. We aimed to evaluate existing and new prediction models for ESD duration.Patients and methods Records of all consecutive patients who underwent single, non-hybrid colorectal ESDs before 2020 at three Dutch centers were reviewed. The performance of an Eastern prediction model [GIE 2021;94(1):133–144] was assessed in the Dutch cohort. A prediction model for procedure duration was built using multivariable linear regression. The model’s performance was validated using internal validation by bootstrap resampling, internal-external cross-validation and external validation in an independent Swedish ESD cohort.Results A total of 435 colorectal ESDs were analyzed (92% en bloc resections, mean duration 139 minutes, mean tumor size 39 mm). The performance of current unstandardized time scheduling practice was suboptimal (explained variance: R2=27%). We successfully validated the Eastern prediction model for colorectal ESD duration <60 minutes (c-statistic 0.70, 95% CI 0.62–0.77), but this model was limited due to dichotomization of the outcome and a relatively low frequency (14%) of ESDs completed <60 minutes in the Dutch centers. The model was more useful with a dichotomization cut-off of 120 minutes (c-statistic: 0.75; 88% and 17% of “easy” and “very difficult” ESDs completed <120 minutes, respectively). To predict ESD duration as continuous outcome, we developed and validated the six-variable cESD-TIME formula (https://cesdtimeformula.shinyapps.io/calculator/; optimism-corrected R2=61%; R2=66% after recalibration of the slope).Conclusions We provided two useful tools for predicting colorectal ESD duration at Western centers. Further improvements and validations are encouraged with potential local adaptation to optimize time planning

Understanding the Critical Needs of Older People: An Aging Perspective

2nd International Conference on Human Aspects of IT for the Aged Population (ITAP) Held as Part of 18th International Conference on Human-Computer Interaction (HCI International), Jul 17-22, 2016, Toronto, CanadaSchool of Desig

A 2a adenosine receptor: Structures, modeling, and medicinal chemistry

Many selective agonists and antagonists of the A 2A adenosine receptor (AR) have been reported, while allosteric modulators specific for this receptor are still needed. Many heterocyclic chemotypes have been discovered as A 2A AR antagonists, while most of the known AR agonists are nucleosides or 3,5-dicyanopyridine derivatives. A few A 2A AR ligands have been in clinical trials as antihypertensives, anti-inflammatory or diagnostic compounds (agonists), and as drugs for treating Parkinson’s disease and cancer (antagonists). The A 2A AR has become one of the most widely investigated G protein-coupled receptor (GPCR) structures using X-ray crystallography and also biophysical techniques such as NMR. Thus, the design of agonists, antagonists, and allosteric modulators has become structure-based, with numerous examples of in silico approaches, including virtual ligand screening (VLS), leading to the discovery of both novel agonists and antagonists

Biochemical and pharmacological role of A1adenosine receptors and their modulation as novel therapeutic strategy

Adenosine, the purine nucleoside, mediates its effects through activation of four G-protein coupled adenosine receptors (ARs) named as A1, A2A, A2Band A3. In particular, A1ARs are distributed through the body, primarily inhibitory in the regulation of adenylyl cyclase activity and able to reduce the cyclic AMP levels. Considerable advances have been made in the pharmacological and molecular characterization of A1ARs, which had been proposed as targets for the discovery and drug design of antagonists, agonists and allosteric enhancers. Several lines of evidence indicate that adenosine interacting with A1ARs may be an endogenous protective agent in the human body since it prevents the damage caused by various pathological conditions, such as in ischemia/hypoxia, epileptic seizures, excitotoxic neuronal injury and cardiac arrhythmias in cardiovascular system. It has also been reported that one of the most promising targets for the development of new anxiolytic drugs could be A1ARs, and that their activation may reduce pain signaling in the spinal cord. A1AR antagonists induce diuresis and natriuresis in various experimental models, mediating the inhibition of A1ARs in the proximal tubule which is primarily responsible for reabsorption and fluid uptake. In addition, the results of various studies indicate that adenosine is present within pancreatic islets and is implicated through A1ARs in the regulation of insulin secretion and in glucose concentrations. In the present paper it will become apparent that A1ARs could be implicated in the pharmacological treatment of several pathologies with an important influence on human health