Neuroprotective effect of mild hypothermia in patients undergoing coronary artery surgery with cardiopulmonary bypass: Five-year follow-up of a randomized trial

ObjectiveIn a randomized trial of 223 patients undergoing coronary artery surgery with cardiopulmonary bypass, we have reported a neuroprotective effect of mild hypothermia. To determine whether the beneficial effect of mild hypothermia was long-lasting, we repeated the psychometric tests in 131 patients after 5 years.MethodsPatients were cooled to 32°C during aortic crossclamping and then randomized to rewarming to either 34°C or 37°C, with no further rewarming until arrival in intensive care unit. Cognitive function was measured preoperatively and 1 week and 5 years postoperatively with a battery of 11 psychometric tests interrogating verbal memory, attention, and psychomotor speed and dexterity.ResultsPatients who had greater cognitive decline 1 week after surgery showed poorer performance 5 years later. The magnitude of cognitive decline over 5 years was modest. The incidence of deficits defined as a 1 standard deviation [SD] decline in at least 1 of 3 factors was not different between temperature groups. Fewer patients in the hypothermic group had deficits that persisted over the 5 years, but this difference did not attain statistical significance (RR = 0.64, P = .16).ConclusionsThe effect of surgery on cognitive function observed early after surgery is an important predictor of cognitive performance 5 years later. Although there was evidence of a neuroprotective effect of mild hypothermia early after surgery in the original cohort, the results after 5 years were inconclusive. In general, the magnitude of cognitive changes over 5 years was modest. We believe that further trials investigating the efficacy of mild hypothermia in patients having cardiac surgery are warranted

The internal thoracic artery skeletonization study: A paired, within-patient comparison [NCT00265499]

BACKGROUND: Traditional harvesting of the internal thoracic artery (ITA) for use as a conduit in coronary bypass surgery involves the dissection of a rim of tissue surrounding the artery on either side. Recent studies, primarily observational, have suggested that skeletonization of the ITA can improve conduit flow, increase length, and reduce the risk of deep sternal infection in high risk patients. Furthermore, skeletonization of the ITA can potentially preserve intercostal nerves and reduce post-operative pain and dysesthesias associated with ITA harvesting. In order to assess the effects of ITA skeletonization, we report a prospective, randomized, within-patient study design that shares many features of a cross-over study. METHODS: Patients undergoing bilateral internal thoracic artery harvest will be randomized to having one side skeletonized and the other harvested in a non-skeletonized manner. Outcome measures include ITA flow and length measured intra-operatively, post-operative pain and dysesthesia, evaluated at discharge, four weeks, and three months post-operatively, and sternal perfusion assessed using single photon emission computed tomography. Harvest times as well as safety endpoints of ITA injury will be recorded. DISCUSSION: This study design, using within-patient comparisons and paired analyses, minimizes the variability of the outcome measures, which is seldom possible in the evaluation of surgical techniques, with minimal chance of carryover effects that can hamper the interpretation of traditional cross-over studies. This study will provide a valid evaluation of clinically relevant effects of internal thoracic artery skeletonization in improving outcomes following coronary artery bypass surgery

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Use of bilateral internal thoracic artery during coronary artery bypass graft surgery in Canada: The bilateral internal thoracic artery survey.

The internal thoracic artery is the gold standard conduit in coronary artery bypass grafting. Although the right and left internal thoracic arteries are excellent conduits, the use of the bilateral internal thoracic artery is not widespread. A recent report of the Society of Thoracic Surgery revealed that only a small percentage of patients receive a bilateral internal thoracic artery in North America. The aim of this study was to determine the current use of the bilateral internal thoracic artery during coronary artery bypass grafting among cardiac surgeons in Canada and identify the main concerns that limit the use of these conduits. We developed an online survey with 17 questions about the use of the bilateral internal thoracic artery in different clinical scenarios. An invitation to participate was sent to all the adult cardiac surgeons currently in practice in Canada. A total of 101 surgeons (69%) of 147 currently in practice across 27 different hospitals completed the survey. Forty percent of surgeons use the bilateral internal thoracic artery only sometimes (6%-25% of cases), 37% of surgeons use the bilateral internal thoracic artery very infrequently (50%). The most common concerns in the use of the bilateral internal thoracic artery are the risk of sternal wound infection and the unknown superiority of the right internal thoracic artery over other conduits. The majority of Canadian cardiac surgeons consider few clinical features, such as insulin-dependent diabetes mellitus or morbid obesity, as contraindications to the use of bilateral internal thoracic artery. However, the reported use of the bilateral internal thoracic artery is low. A wider diffusion of this technique is warranted to improve the results of coronary surgery