Intraoperative Oxidative Damage and Delirium after Cardiac Surgery.

BACKGROUND: Mechanisms of postoperative delirium remain poorly understood, limiting development of effective treatments. We tested the hypothesis that intraoperative oxidative damage is associated with delirium and neuronal injury and that disruption of the blood-brain barrier modifies these associations. METHODS: In a prespecified cohort study of 400 cardiac surgery patients enrolled in a clinical trial of atorvastatin to reduce kidney injury and delirium, we measured plasma concentrations of F2-isoprostanes and isofurans using gas chromatography-mass spectrometry to quantify oxidative damage, ubiquitin carboxyl-terminal hydrolase isozyme L1 to quantify neuronal injury, and S100 calcium-binding protein B using enzyme-linked immunosorbent assays to quantify blood-brain barrier disruption before, during, and after surgery. We performed the Confusion Assessment Method for the Intensive Care Unit twice daily to diagnose delirium. We measured the independent associations between intraoperative F2-isoprostanes and isofurans and delirium (primary outcome) and postoperative ubiquitin carboxyl-terminal hydrolase isozyme L1 (secondary outcome), and we assessed if S100 calcium-binding protein B modified these associations. RESULTS: Delirium occurred in 109 of 400 (27.3%) patients for a median (10th, 90th percentile) of 1.0 (0.5, 3.0) days. In the total cohort, plasma ubiquitin carboxyl-terminal hydrolase isozyme L1 concentration was 6.3 ng/ml (2.7, 14.9) at baseline and 12.4 ng/ml (7.9, 31.2) on postoperative day 1. F2-isoprostanes and isofurans increased throughout surgery, and the log-transformed sum of intraoperative F2-isoprostanes and isofurans was independently associated with increased odds of postoperative delirium (odds ratio, 3.70 [95% CI, 1.41 to 9.70]; P = 0.008) and with increased postoperative ubiquitin carboxyl-terminal hydrolase isozyme L1 (ratio of geometric means, 1.42 [1.11 to 1.81]; P = 0.005). The association between increased intraoperative F2-isoprostanes and isofurans and increased postoperative ubiquitin carboxyl-terminal hydrolase isozyme L1 was amplified in patients with elevated S100 calcium-binding protein B (P = 0.049). CONCLUSIONS: Intraoperative oxidative damage was associated with increased postoperative delirium and neuronal injury, and the association between oxidative damage and neuronal injury was stronger among patients with increased blood-brain barrier disruption.

Risk factors for delirium after cardiac surgery: a historical cohort study outlining the influence of cardiopulmonary bypass.

PURPOSE: Cardiopulmonary bypass (CPB) induces a significant inflammatory response that may increase the risk for delirium. We hypothesized that exposure to CPB during coronary artery bypass grafting (CABG) surgery would correlate with an increased risk of delirium. METHODS: We reviewed clinical data from two databases at our medical centre - the Cardiac Surgery Perioperative Outcomes Database and the Society of Thoracic Surgeons Database. Patients undergoing elective CABG surgery (on-pump and off-pump) from November 1, 2009 to September 30, 2015 were included in the study. Delirium was defined as any postoperative positive Confusion Assessment Method for the Intensive Care Unit exam during the intensive care unit stay. We performed logistic regression to isolate the association between CPB exposure and delirium adjusted for predetermined risk factors and potential confounders. RESULTS: During the study period, 2,280 patients underwent elective CABG surgery, with 384 patients (16.9%) exposed to CPB. Delirium was diagnosed in 451 patients (19.8%). Exposure to CPB showed a significant independent association with delirium. Patients exposed to CPB for 142 min (90th percentile of CPB duration) vs those exposed for 54 min (10th percentile) had an adjusted relative risk (RR) of delirium of 2.18 (95% confidence interval [CI], 1.39 to 3.07; P = 0.002) vs a RR of 1.51 (95% CI, 0.92 to 2.29; P = 0.10), respectively. CONCLUSIONS: The use and duration of cardiopulmonary bypass were associated with an increased risk of delirium in patients undergoing CABG surgery. TRIAL REGISTRATION: www.clinicaltrials.gov , NCT02548975. Registered 4 September 2015.

Intravenous vs Oral Acetaminophen as an Adjunct to Multimodal Analgesia After Total Knee Arthroplasty: A Prospective, Randomized, Double-Blind Clinical Trial.

BACKGROUND: The efficacy of intravenous (IV) acetaminophen compared with its oral formulation for postoperative analgesia is unknown. We hypothesized that the addition of acetaminophen to a multimodal analgesia regimen would provide improved pain management in patients after total knee arthroplasty (TKA) and that the effect of acetaminophen would be variable based on the route of delivery. METHODS: The study was a single-center, randomized, double-blinded, placebo-controlled clinical trial on the efficacy of IV vs oral acetaminophen in patients undergoing unilateral TKA. One hundred seventy-four subjects were randomized to one of the 3 groups: IV acetaminophen group (IV group, n = 57) received 1 g IV acetaminophen and oral placebo before postanesthesia care unit (PACU) admission; oral acetaminophen group (PO group, n = 58) received 1 g oral acetaminophen and volume-matched IV normal saline; placebo group (Placebo group, n = 59) received oral placebo and volume-matched IV normal saline. Pain scores were obtained every 15 minutes during PACU stay. Average pain scores, maximum pain score, and pain scores before physical therapy were compared among the 3 groups. Secondary outcomes included total opiate consumption, time to PACU discharge, time to rescue analgesia, and time to breakthrough pain. RESULTS: The average PACU pain score was similar in the IV group (0.56 ± 0.99 [mean ± standard deviation]) compared with the PO group (0.67 ± 1.20; P = .84) and Placebo group (0.58 ± 0.99; P = .71). Total opiate consumption at 6 hours (0.47 mg hydromorphone equivalents ± 0.56 vs 0.54 ± 0.53 vs 0.54 ± 0.61; P = .69) and at 24 hours (1.25 ± 1.30 vs 1.49 ± 1.34 vs 1.36 ± 1.31; P = .46) were also similar between the IV, PO, and Placebo groups. No significant differences were found between all groups for any other outcome. CONCLUSION: Neither IV nor oral acetaminophen provides additional analgesia in the immediate postoperative period when administered as an adjunct to multimodal analgesia in patients undergoing TKA in the setting of a spinal anesthetic.

Acute kidney injury following cardiac surgery: current understanding and future directions.

Acute kidney injury (AKI) complicates recovery from cardiac surgery in up to 30 % of patients, injures and impairs the function of the brain, lungs, and gut, and places patients at a 5-fold increased risk of death during hospitalization. Renal ischemia, reperfusion, inflammation, hemolysis, oxidative stress, cholesterol emboli, and toxins contribute to the development and progression of AKI. Preventive strategies are limited, but current evidence supports maintenance of renal perfusion and intravascular volume while avoiding venous congestion, administration of balanced salt as opposed to high-chloride intravenous fluids, and the avoidance or limitation of cardiopulmonary bypass exposure. AKI that requires renal replacement therapy occurs in 2-5 % of patients following cardiac surgery and is associated with 50 % mortality. For those who recover from renal replacement therapy or even mild AKI, progression to chronic kidney disease in the ensuing months and years is more likely than for those who do not develop AKI. Cardiac surgery continues to be a popular clinical model to evaluate novel therapeutics, off-label use of existing medications, and nonpharmacologic treatments for AKI, since cardiac surgery is fairly common, typically elective, provides a relatively standardized insult, and patients remain hospitalized and monitored following surgery. More efficient and time-sensitive methods to diagnose AKI are imperative to reduce this negative outcome. The discovery and validation of renal damage biomarkers should in time supplant creatinine-based criteria for the clinical diagnosis of AKI.

Seasonal Incidence of Emergent Coronary Artery Bypass Grafting Surgery.

BACKGROUND: Emergent coronary artery bypass grafting (CABG) surgery is often required in the case of severe coronary artery disease, which is refractory to traditional management. The objective of our study was to test the hypothesis that there is seasonal variation in the incidence of emergent CABG. METHODS: A sinusoidal logistic regression model was used to analyze operative data at our cardiovascular institute of 270 cases spanning 5939 calendar days. RESULTS: A cyclic peak risk for emergent CABG was observed for late winter (calendar day 66; P = .036). The odds ratios for the 1-, 2- and 3-month window surrounding this peak were 1.8 (95% CI = 0.94-3.5, P = .072), 1.6 (95% CI = 1.06-2.5, P = .024) and 1.4 (95% CI = 0.9-1.8, P = .066), respectively. CONCLUSION: Our results suggest that a seasonal variation may exist in the incidence of patients presenting with severe coronary artery disease requiring emergent CABG. This information is useful in the scheduling of hospital resources and staff. It also provides important etiology clues underlying coronary artery disease that may lead to future interventions or targeted therapies.

Goal-directed therapy in the operating room: is there any benefit?

PURPOSE OF REVIEW: This article reviews the current evidence behind goal-directed therapy (GDT) in multiple medical settings. RECENT FINDINGS: Although some studies advocate for the use of GDT, others do not and more studies are necessary to evaluate the efficacy of GDT in medicine. Previously accepted guidelines for treating patients in septic shock which include GDT in their algorithms are not supported by the findings in recent randomized, controlled trials. No generally accepted guidelines for GDT are available for perioperative use, but there is evidence supporting GDT in high-risk surgery such as major abdominal surgery and cardiac surgery. Clinicians should be aware of the potential benefits of GDT in these settings and use these evidence-based findings to help guide clinical decisions in these patient populations. SUMMARY: The use of GDT may be beneficial depending on the clinical setting, but more evidence supporting its use is necessary before it can be considered standard of care.

Morphometric variability of neuroimaging features in children with agenesis of the corpus callosum.

BACKGROUND: Agenesis of the corpus callosum (ACC) is a developmental brain malformation associated with a wide spectrum of structural brain abnormalities and genetic loci. To characterize the diverse callosal morphologies and malformations of brain development associated with ACC, we report on the neuroimaging findings of 201 individuals diagnosed with corpus callosal abnormalities. METHODS: We searched through medical records of individuals seen at New York Presbyterian Hospital between 2002 and 2013 and thought to have ACC. We confirmed 201 individuals meeting criteria and used magnetic resonance imaging to characterize morphological variants of the corpus callosum and associated brain malformations. RESULTS: The majority of individuals displayed hypoplasia or dysplasia of the corpus callosum (N = 160, 80 %). Forty-one (20 %) displayed complete agenesis of the corpus callosum with other abnormalities, while only 18 (9 %) displayed complete agenesis without associated brain abnormalities. White matter abnormalities were more frequent in hypoplasia or dysplasia group than complete agenesis (28.2 % vs 9.8 %, p < 0.05). In contrast, hippocampal abnormalities, colpocephaly, and Probst bundles were significantly more frequent in complete agenesis compared to hypoplasia or dysplasia group. CONCLUSIONS: Collectively, our results underscore the broad diversity of morphological variants of the corpus callosum and associated brain abnormalities in individuals with ACC.

Filamin A regulates neuronal migration through brefeldin A-inhibited guanine exchange factor 2-dependent Arf1 activation.

Periventricular heterotopias is a malformation of cortical development, characterized by ectopic neuronal nodules around ventricle lining and caused by an initial migration defect during early brain development. Human mutations in the Filamin A (FLNA) and ADP-ribosylation factor guanine exchange factor 2 [ARFGEF2; encoding brefeldin-A-inhibited guanine exchange factor-2 (BIG2)] genes give rise to this disorder. Previously, we have reported that Big2 inhibition impairs neuronal migration and binds to FlnA, and its loss promotes FlnA phosphorylation. FlnA phosphorylation dictates FlnA-actin binding affinity and consequently alters focal adhesion size and number to effect neuronal migration. Here we show that FlnA loss similarly impairs migration, reciprocally enhances Big2 expression, but also alters Big2 subcellular localization in both null and conditional FlnA mice. FlnA phosphorylation promotes relocalization of Big2 from the Golgi toward the lipid ruffles, thereby activating Big2-dependent Arf1 at the cell membrane. Loss of FlnA phosphorylation or Big2 function impairs Arf1-dependent vesicle trafficking at the periphery, and Arf1 is required for maintenance of cell-cell junction connectivity and focal adhesion assembly. Loss of Arf1 activity disrupts neuronal migration and cell adhesion. Collectively, these studies demonstrate a potential mechanism whereby coordinated interactions between actin (through FlnA) and vesicle trafficking (through Big2-Arf) direct the assembly and disassembly of membrane protein complexes required for neuronal migration and neuroependymal integrity.

Race and survival among diabetic patients after coronary artery bypass grafting.

BACKGROUND: Diabetes is a known predictor of decreased long-term survival after coronary artery bypass grafting (CABG). Differences in survival by race have not been examined. METHODS: A retrospective cohort study was conducted for CABG patients between 1992 and 2011. Long-term survival was compared in patients with and without diabetes and stratified by race. Hazard ratios (HR) and 95% confidence intervals (CI) were computed using a Cox regression model. RESULTS: Out of the 13,053 patients undergoing CABG, 35% (black n = 1,655; white n = 2,884) had diabetes at the time of surgery. The median follow-up for study participants was 8.2 years. Long-term survival after CABG was similar between black and white diabetic patients (no diabetes, HR = 1.0; white diabetic patients, adjusted HR = 1.5, 95%CI = 1.4-1.6; black diabetic patients, adjusted HR = 1.5, 95%CI = 1.4-1.7). CONCLUSION: A survival disadvantage after CABG was not observed among black versus white diabetic patients in our study.

The effect of preoperative ß-blocker use and race on long-term survival after coronary artery bypass grafting.

OBJECTIVE: To date, racial differences in the long-term survival of coronary artery bypass grafting (CABG) patients who receive preoperative ß-blockers have not been specifically examined. The purpose of this study was to examine the effect of preoperative ß-blockers on long-term survival among black CABG patients and to compare the magnitude of this effect with white patients. DESIGN: A retrospective cohort study. SETTING: A tertiary referral heart hospital. PARTICIPANTS: 13,354 patients undergoing CABG between 1992 and 2011. MEASUREMENTS AND MAIN RESULTS: Hazard ratios (HR) and 95% confidence intervals (CI) were computed using a Cox regression model. A total of 1,448 (62%) black and 6,094 (55%) white patients had a history of preoperative ß-blocker use. Among black patients, those receiving ß-blockers survived longer than those not receiving ß-blockers (adjusted HR = 0.77, 95% CI = 0.67-0.88). The survival advantage was comparable to that observed among white patients (adjusted HR = 0.88, 95% CI = 0.82-0.93). CONCLUSION: Black CABG patients benefited from preoperative ß-blockers and the magnitude of the effect was comparable to that among white patients.

Operative status and survival after coronary artery bypass grafting.

BACKGROUND: The effect of race on long-term survival of patients undergoing elective and nonelective coronary artery bypass grafting (CABG) is currently unknown. The purpose of this study was to compare long-term survival between black and white CABG patients by operative status. METHODS: Long-term survival of black versus white patients undergoing elective and nonelective CABG procedures between 1992 and 2011 was compared. Survival probabilities were computed using the Kaplan-Meier product-limit method and stratified by race. Hazard ratios (HR) and 95% confidence intervals (CI) were computed using a Cox regression model. RESULTS: A total of 13,774 patients were included in this study. The median follow-up time for study participants was 8.2 years. Black patients undergoing elective CABG died sooner than whites (adjusted HR = 1.4, 95% CI = 1.2-1.5). Survival was similar between blacks and whites in the nonelective population (adjusted HR = 1.0, 95% CI = 0.96-1.1). CONCLUSIONS: Black race was a statistically significant predictor of long-term survival after elective but not nonelective CABG.

Brefeldin A-inhibited guanine exchange factor 2 regulates filamin A phosphorylation and neuronal migration.

Periventricular heterotopia (PH) is a human malformation of cortical development associated with gene mutations in ADP-ribosylation factor guanine exchange factor 2 (ARFGEF2 encodes for Big2 protein) and Filamin A (FLNA). PH is thought to derive from neuroependymal disruption, but the extent to which neuronal migration contributes to this phenotype is unknown. Here, we show that Arfgef2 null mice develop PH and exhibit impaired neural migration with increased protein expression for both FlnA and phosphoFlnA at Ser2152. Big2 physically interacts with FlnA and overexpression of phosphomimetic Ser2512 FLNA impairs neuronal migration. FlnA phosphorylation directs FlnA localization toward the cell cytoplasm, diminishes its binding affinity to actin skeleton, and alters the number and size of paxillin focal adhesions. Collectively, our results demonstrate a molecular mechanism whereby Big2 inhibition promotes phosphoFlnA (Ser2152) expression, and increased phosphoFlnA impairs its actin binding affinity and the distribution of focal adhesions, thereby disrupting cell intrinsic neuronal migration.

Impact of race and postoperative atrial fibrillation on long-term survival after coronary artery bypass grafting.

BACKGROUND AND AIM: Postoperative atrial fibrillation (POAF) is a known predictor of in-hospital morbidity and short-term survival after coronary artery bypass grafting (CABG). The impact of race and long-term survival has not been examined in this population. We aimed to examine the influence of these factors on long-term survival in patients undergoing CABG. METHODS: Patients undergoing first-time, isolated CABG between 1992 and 2011 were included in this study. Long-term survival was compared in patients with and without POAF and stratified by race. Hazard ratios (HR) and 95% confidence intervals (CI) were computed using a Cox regression model. RESULTS: A total of 2,907 (22%) patients developed POAF (black n=370; white n=2,537) following CABG (N=13,165). Median follow-up for study participants was 8.2 years. Long-term survival after CABG differed by POAF status and race (no POAF: HR=1.0; white POAF: adjusted HR=1.1, 95% CI=1.06-1.2; black POAF: adjusted HR=1.4, 95% CI=1.2-1.6; pTrend=0.0002). lack POAF patients also died sooner after surgery than their white counterparts (adjusted HR=1.2, 95% CI=1.02-1.4). CONCLUSION: Black race was a statistically significant predictor of decreased survival among POAF patients after CABG. This finding provides useful outcome information for surgeons and their patients.

The impact of prior percutaneous coronary intervention on long-term survival after coronary artery bypass grafting.

BACKGROUND: Previous studies examining the influence of prior percutaneous coronary intervention (PCI) on long-term survival after coronary artery bypass grafting (CABG) have reported conflicting results. The purpose of this study was to further examine the influence of prior PCI on long-term survival after CABG at a large tertiary referral heart institute. METHODS: Long-term survival between 1992 and 2011 was compared in non-emergent CABG cases with and without prior PCI. Hazard ratios (HR) and 95% confidence intervals (CI) were computed using a Cox regression model. RESULTS: A total of 2532 (19%) patients had prior PCI before CABG (n=13,354). The median follow-up for study participants was 8.1 years. The median survival for patients with and without prior PCI was 15 years and 14 years, respectively (p<0.0001). Long-term survival was similar between patients with and without prior PCI after adjusting for age, sex, race, hypertension, coronary artery disease severity, congestive heart failure, and prior stroke (adjusted HR=0.99, 95%CI=0.91-1.06). CONCLUSION: Findings from outcomes research are important in the planning of appropriate postoperative patient care. Our study provides additional evidence that prior PCI is not a significant predictor of long-term survival after CABG.

Rab7a activation promotes degradation of select tight junction proteins at the blood-brain barrier after ischemic stroke.

The stability of tight junctions (TJs) between endothelial cells (ECs) is essential to maintain blood-brain barrier (BBB) function in the healthy brain. Following ischemic stroke, TJ strand dismantlement due to protein degradation leads to BBB dysfunction, yet the mechanisms driving this process are poorly understood. Here, we show that endothelial-specific ablation of Rab7a, a small GTPase that regulates endolysosomal protein degradation, reduces stroke-induced TJ strand disassembly resulting in decreased paracellular BBB permeability and improved neuronal outcomes. Two pro-inflammatory cytokines, TNFα and IL1ß, but not glucose and oxygen deprivation, induce Rab7a activation via Ccz1 in brain ECs in vitro, leading to increased TJ protein degradation and impaired paracellular barrier function. Silencing Rab7a in brain ECs in vitro reduces cytokine-driven endothelial barrier dysfunction by suppressing degradation of a key BBB TJ protein, Claudin-5. Thus, Rab7a activation by inflammatory cytokines promotes degradation of select TJ proteins leading to BBB dysfunction after ischemic stroke.

Disruption of neural progenitors along the ventricular and subventricular zones in periventricular heterotopia.

Periventricular heterotopia (PH) is a disorder characterized by neuronal nodules, ectopically positioned along the lateral ventricles of the cerebral cortex. Mutations in either of two human genes, Filamin A (FLNA) or ADP-ribosylation factor guanine exchange factor 2 (ARFGEF2), cause PH (Fox et al. in 'Mutations in filamin 1 prevent migration of cerebral cortical neurons in human periventricular heterotopia'. Neuron, 21, 1315-1325, 1998; Sheen et al. in 'Mutations in ARFGEF2 implicate vesicle trafficking in neural progenitor proliferation and migration in the human cerebral cortex'. Nat. Genet., 36, 69-76, 2004). Recent studies have shown that mutations in mitogen-activated protein kinase kinase kinase-4 (Mekk4), an indirect interactor with FlnA, also lead to periventricular nodule formation in mice (Sarkisian et al. in 'MEKK4 signaling regulates filamin expression and neuronal migration'. Neuron, 52, 789-801, 2006). Here we show that neurons in post-mortem human PH brains migrated appropriately into the cortex, that periventricular nodules were primarily composed of later-born neurons, and that the neuroependyma was disrupted in all PH cases. As studied in the mouse, loss of FlnA or Big2 function in neural precursors impaired neuronal migration from the germinal zone, disrupted cell adhesion and compromised neuroepithelial integrity. Finally, the hydrocephalus with hop gait (hyh) mouse, which harbors a mutation in Napa [encoding N-ethylmaleimide-sensitive factor attachment protein alpha (alpha-SNAP)], also develops a progressive denudation of the neuroepithelium, leading to periventricular nodule formation. Previous studies have shown that Arfgef2 and Napa direct vesicle trafficking and fusion, whereas FlnA associates dynamically with the Golgi membranes during budding and trafficking of transport vesicles. Our current findings suggest that PH formation arises from a final common pathway involving disruption of vesicle trafficking, leading to impaired cell adhesion and loss of neuroependymal integrity.

Intraoperative prediction of cardiac surgery-associated acute kidney injury using urinary biomarkers of cell cycle arrest.

OBJECTIVE: Tissue inhibitor of metalloproteinases 2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) are postoperative urinary biomarkers of renal stress and acute kidney injury (AKI). We conducted this study to test the hypothesis that intraoperative concentrations of urinary [TIMP-2]·[IGFBP7] are associated with postoperative AKI. METHODS: We measured urinary [TIMP-2]·[IGFBP7] at 8 perioperative timepoints in 400 patients who participated in a randomized controlled trial of atorvastatin for AKI in cardiac surgery. We compared [TIMP-2]·[IGFBP7] between subjects who did and did not develop KDIGO stage 2 or 3 AKI within 48 hours of surgery, adjusted for AKI risk factors. RESULTS: Fourteen patients (3.5%) met the primary endpoint of stage 2 or 3 AKI within 48 hours of surgery, and an additional 77 patients (19.3%) developed stage 1 AKI. Patients who developed stage 2 or 3 AKI displayed bimodal elevations of [TIMP-2]·[IGFBP7], with a first elevation (median, 0.45 [ng/mL]2/1000) intraoperatively and a second elevation (1.45 [ng/mL]2/1000) 6 hours postoperatively. Patients who did not develop AKI did not have any elevations in [TIMP-2]·[IGFBP7]. Each 10-fold increase in intraoperative [TIMP-2]·[IGFBP7] was independently associated with a 290% increase in the odds of stage 2 or 3 AKI (P = .01), and each 10-fold increase in the 6 hours postoperative [TIMP-2]·[IGFBP7] was independently associated with a 650% increase in the odds of stage 2 or 3 AKI (P < .001). The maximum [TIMP-2]·[IGFBP7] between these 2 timepoints provided an area under the receiver operating characteristic curve of 0.82 (95% confidence interval [CI], 0.73-0.90), 100% sensitivity, and 100% negative predictive value using the >0.3 cutoff to predict stage 2 or 3 AKI. CONCLUSIONS: Intraoperative elevations of [TIMP-2]·[IGFBP7] can predict moderate or severe AKI and could provide an opportunity to alter postoperative management to prevent kidney injury.

The use of dexmedetomidine and intravenous acetaminophen for the prevention of postoperative delirium in cardiac surgery patients over 60 years of age: a pilot study.

Background: Delirium is associated with many negative health outcomes. Postoperative sedation and opioid administration may contribute to delirium. We hypothesize that the use of dexmedetomidine and Intravenous acetaminophen (IVA) may lead to reduced opioid consumption and decreased incidence of postoperative delirium. This pilot study aims to assess feasibility of using dexmedetomidine and IVA in cardiac surgical patients, and obtain effect size estimates for incidence and duration of delirium. Methods: A total of 12 adult patients >60 years of age undergoing cardiac surgery were recruited for the study after IRB approval and randomized into 4 groups: Propofol only (P), Propofol with IVA (P+A), Dexmedetomidine only (D), Dexmedetomidine with IVA (D+A). Preoperative baseline cognition and postoperative delirium was assessed daily until discharge. The feasibility was assessed by the number of patients who successfully completed the study. Results: All patients completed the study protocol successfully. The total incidence of delirium in the study population was 42% (5/12):  67% (2/3) in the group P, and 67% (2/3) in the group D, 33% (1/3) in  D+A group and 0%(0/3)  P+A group. The incidence of delirium was 17% (1/6) in the group receiving IVA compared to 67% (4/6) that did not receive IVA. The mean duration of delirium was 0-1 days. One patient expired after surgery, unrelated to the study protocol. One patient in the D group experienced hypotension with systolic blood pressure <90 mm of Hg. Conclusions: The feasibility of performing a large-scale project is ascertained by the study. Patients receiving IVA had lower incidence of delirium compared to patients not receiving IVA which suggests that IVA may have a role in reducing the incidence of delirium. A prospective randomized, placebo-controlled trial will be the next step in investigating the role of dexmedetomidine and IVA in reducing the incidence of delirium.

Effect of Preoperative Beta-Blocker Use on Outcomes Following Cardiac Surgery.

Recent studies suggest that the use of preoperative ß blockers in cardiac surgery may not provide improved mortality rates and may even contribute to negative clinical outcomes. We therefore assessed the role of ß blockers on several outcomes after cardiac surgery (delirium, acute kidney injury [AKI], stroke, atrial fibrillation (AF), mortality, and hospital length of stay) in 4,076 patients who underwent elective coronary artery bypass grafting, coronary artery bypass grafting + valve, or valve cardiac surgery from November 1, 2009, to September 30, 2015, at Vanderbilt Medical Center. Clinical data from 2 prospectively collected datasets at our institution were reviewed: the Cardiac Surgery Perioperative Outcomes Database and the Society of Thoracic Surgeons Database. Preoperative ß-blocker use was defined by Society of Thoracic Surgeons guidelines as patients receiving a ß blocker within 24 hours preceding surgery. Of the included patients, 2,648 (65.0%) were administered a ß blocker within 24 hours before surgery. Adjusting for possible confounders, preoperative ß-blocker use was associated with increased odds of AKI stage 2 (odds ratio 1.96, 95% confidence interval 1.19 to 3.24, p <0.01). There was no evidence that ß-blocker use had an independent association with postoperative delirium, AKI stages 1 and 3, stroke, AF, mortality, or prolonged length of stay. A secondary propensity score analysis did not show a marginal association between ß-blocker use and any outcome. In conclusion, we did not find significant evidence that preoperative ß-blocker use was associated with postoperative delirium, AF, AKI, stroke, or mortality.

Cerebellar ataxia with progressive improvement.

BACKGROUND: Nonprogressive cerebellar ataxias are characterized by a persistent, nonprogressive ataxia associated with cognitive impairment. Cerebellar hypoplasia on imaging is variable but is not predictive of the degree of ataxia or cognitive impairment. OBJECTIVE: To describe a family with a nonprogressive cerebellar ataxia associated with cognitive and motor impairments that improve with age. DESIGN: Genetic study in a family with nonprogressive cerebellar ataxia. Clinical and imaging features are also described. SETTING: Community hospital. PATIENTS: Both parents and 3 children from an affected family. MAIN OUTCOME MEASURES: Clinical features, magnetic resonance imaging findings, and genetic findings. RESULTS: A genome-wide single nucleotide polymorphism screen did not show clear linkage to known spinocerebellar ataxia loci, in particular spinocerebellar ataxia type 15. Repeat spinocerebellar ataxia loci expansions were excluded. Magnetic resonance images of all affected individuals demonstrated cerebellar vermian abnormalities. CONCLUSIONS: These findings suggest that nonprogressive cerebellar ataxia is genetically heterogeneous and, when associated with gradual improvement in cognition and motor skills, likely represents a separate, distinct clinical entity.