ISRCTN93543537.

IMPORTANCE Postoperative delirium in older adults is a common and costly complication after surgery. Cognitive reserve affects the risk of postoperative delirium, and thus preoperative augmentation of reserve as a preventive technique is of vital interest. OBJECTIVE To determine whether cognitive prehabilitation reduces the incidence of postoperative delirium among older adults. DESIGN, SETTING, AND PARTICIPANTS This was a prospective, single-blinded randomized clinical trial conducted from March 2015 to August 2019 at the Ohio State University Wexner Medical Center in Columbus. Patients 60 years and older undergoing major, noncardiac, nonneurological surgery under general anesthesia, with an expected hospital stay of at least 72 hours, were eligible for trial inclusion. Patients were excluded for preoperative cognitive dysfunction and active depression. INTERVENTIONS Participation in electronic, tablet-based preoperative cognitive exercise targeting memory, speed, attention, flexibility, and problem-solving functions. MAIN OUTCOMES AND MEASURESThe primary outcome was incidence of delirium between postoperative day 0 to day 7 or discharge, as measured by a brief Confusion Assessment Method, Memorial Delirium Assessment Scale, or a structured medical record review. Secondary outcomes compared delirium characteristics between patients in the intervention and control groups. RESULTSOf the 699 patients approached for trial participation, 322 completed consent and 268 were randomized. Subsequently, 17 patients were excluded, leaving 251 patients in the primary outcome analysis. A total of 125 patients in the intervention group and 126 control patients were included in the final analysis (median [interquartile range] age, 67 [63][64][65][66][67][68][69][70][71] years; 163 women [64.9%]). Ninety-seven percent of the patients in the intervention group completed some brain exercise (median, 4.6 [interquartile range, 1.31-7.4] hours). The delirium rate among control participants was 23.0% (29 of 126). With intention-to-treat analysis, the delirium rate in the intervention group was 14.4% (18 of 125; P = .08). Post hoc analysis removed 4 patients who did not attempt any cognitive exercise from the intervention group, yielding a delirium rate of 13.2% (16 of 121; P = .04). Secondary analyses among patients with delirium showed no differences in postoperative delirium onset day or duration or total delirium-positive days across study groups. CONCLUSIONS AND RELEVANCEThe intervention lowered delirium risk in patients who were at least minimally compliant. The ideal activities, timing, and effective dosage for cognitive exercise-based interventions to decrease postoperative delirium risk and burden need further study.

Enterochromaffin (EC) cells synthesize 95% of the body 5-HT and release 5-HT in response to mechanical or chemical stimulation. EC cell 5-HT has physiological effects on gut motility, secretion and visceral sensation. Abnormal regulation of 5-HT occurs in gastrointestinal disorders and Inflammatory Bowel Diseases (IBD) where 5-HT may represent a key player in the pathogenesis of intestinal inflammation. The focus of this review is on mechanism(s) involved in EC cell “mechanosensation” and critical gaps in our knowledge for future research. Much of our knowledge and concepts are from a human BON cell model of EC, although more recent work has included other cell lines, native EC cells from mouse and human and intact mucosa. EC cells are “mechanosensors” that respond to physical forces generated during peristaltic activity by translating the mechanical stimulus (MS) into an intracellular biochemical response leading to 5-HT and ATP release. The emerging picture of mechanosensation includes Piezo 2 channels, caveolin-rich microdomains, and tight regulation of 5-HT release by purines. The “purinergic hypothesis” is that MS releases purines to act in an autocrine/paracrine manner to activate excitatory (P2Y1, P2Y4, P2Y6, and A2A/A2B) or inhibitory (P2Y12, A1, and A3) receptors to regulate 5-HT release. MS activates a P2Y1/Gαq/PLC/IP3-IP3R/SERCA Ca2+signaling pathway, an A2A/A2B–Gs/AC/cAMP-PKA signaling pathway, an ATP-gated P2X3 channel, and an inhibitory P2Y12-Gi/o/AC-cAMP pathway. In human IBD, P2X3 is down regulated and A2B is up regulated in EC cells, but the pathophysiological consequences of abnormal mechanosensory or purinergic 5-HT signaling remain unknown. EC cell mechanosensation remains poorly understood.

BackgroundClevidipine is an ultrashort-acting drug for rapid reduction of blood pressure by selectively acting on the L-type Ca2+ channels on arteriolar smooth muscle. The drug’s ultrashort action in reducing the blood pressure is due to its rapid hydrolysis by blood and extravascular tissue esterases, which does not depend on hepato-renal metabolism and excretion. An analysis of the perioperative management of blood pressure should be considered to compare with other intravenous antihypertensive agents.MethodsAnalyses of the available evidence in randomized clinical trials following the PRISMA methodology as well as clinical significance according to the GRADE system were conducted. Placebo versus other antihypertensive drugs studies were included. Statistical assessments were done using the X2 and I2 tests.ResultsClevidipine was more effective in maintaining the blood pressure within pre-specified ranges compared with other antihypertensive drugs (MD, -17.87 CI 95%: -29.02 to -6.72; p = 0.02). The use of Clevidipine versus placebo and rescue antihypertensive intravenous drug showed a clear reduction in rates of treatment failure (RR 0.10; IC 95%; 0.05–0.18; p <0.0001). There was no difference in the incidence of adverse events compared with placebo (RR 1.47; 95% CI 0.89 to 2.43, p = 0.14) and with other antihypertensive drugs (RR 0.78, 95% CI 0.45 to 1.35; p = 0.37). In addition, there was no difference in the incidence of atrial fibrillation (AF) between clevidipine and control groups (RR 1.09, IC del 95%: 0.65 a 1.83; p = 0.73).ConclusionsClevidipine is an ultrafast-acting drug that is highly effective for management of perioperative arterial hypertension. It is devoid of adverse effects associated with the use of other IV antihypertensives. Its favorable pharmacodynamic and pharmacokinetic properties make clevidipine the drug of choice for the management of acute perioperative hypertension. It is important to emphasize the need for further studies with a larger number of patients to confirm these findings and increase the degree of evidence.