Intraoperative neurological pupil index and postoperative delirium and neurologic adverse events after cardiac surgery: an observational study.

Neurological pupil index (NPi) calculated by automated pupillometry predicts clinical outcomes in critically ill patients. However, there are few data on intraoperative NPi and postoperative outcome after cardiac surgery. We evaluated the relationships between intraoperative NPi and clinical outcomes, such as delirium, in cardiac surgery patients. NPi was measured at baseline, after anesthesia induction, at 30 min intervals after initiation of cardiopulmonary bypass or anastomosis of coronary artery bypass graft, and at skin closure. Abnormal NPi was defined as one or more measurements of NPi < 3.0 during surgery. The worst intraoperative NPi was recorded, then multivariate logistic regression analysis was performed to evaluate the relationship between abnormal NPi and postoperative delirium following cardiac surgery. Among 123 included patients, postoperative delirium developed in 19.5% (24/123) of patients. Intraoperative abnormal NPi was significantly associated with postoperative delirium (odds ratio 6.078; 95% confidence interval 1.845-20.025; P = 0.003) after adjustment for Society of Thoracic Surgeons Predicted Risk of Mortality score, coronary artery disease, and use of calcium channel blockers. In conclusion, abnormal intraoperative NPi independently predicted postoperative delirium following cardiac surgery. Intraoperative application of pupillometry may have prognostic value for development of postoperative delirium, thereby enabling close surveillance and early intervention in high-risk patients.Registry number: ClinicalTrials.gov (NCT04136210).

Effects of transcutaneous electrical nerve stimulation on myocardial protection in patients undergoing aortic valve replacement: a randomized clinical trial.

BACKGROUND: Cardiopulmonary bypass-related myocardial ischemia-reperfusion injury is a major contributor to postoperative morbidity. Although transcutaneous electrical nerve stimulation (TENS) has been found to have cardioprotective effects in animal studies and healthy volunteers, its effects on cardiac surgery under cardiopulmonary bypass patients have not been evaluated. We investigated the effects of TENS on myocardial protection in patients undergoing aortic valve replacement surgery using cardiopulmonary bypass. METHODS: Thirty patients were randomized to receive TENS or sham in three different anesthetic states - pre-anesthesia, sevoflurane, or propofol (each n = 5). TENS was applied with a pulse width of 385 µs and a frequency of 10 Hz using two surface electrodes at the upper arm for 30 min. Sham treatment was provided without stimulation. The primary outcome was the difference in myocardial infarct size following ischemia-reperfusion injury in rat hearts perfused with pre- and post-TENS plasma dialysate obtained from the patients using Langendorff perfusion system. The cardioprotective effects of TENS were determined by assessing reduction in infarct size following treatment. RESULTS: There were no differences in myocardial infarct size between pre- and post-treatment in any group (41.4 ± 4.3% vs. 36.7 ± 5.3%, 39.8 ± 7.3% vs. 27.8 ± 12.0%, and 41.6 ± 2.2% vs. 37.8 ± 7.6%; p = 0.080, 0.152, and 0.353 in the pre-anesthesia, sevoflurane, and propofol groups, respectively). CONCLUSIONS: In our study, TENS did not show a cardioprotective effect in patients undergoing aortic valve replacement surgery. TRIAL REGISTRATION: This study was registered at clinicaltrials.gov ( NCT03859115 , on March 1, 2019).

Heart rate variability and oxygen reserve index during cardiorespiratory events in patients undergoing ophthalmic arterial chemotherapy: a prospective observational study.

Unexpected cardiorespiratory compromise has been reported during ophthalmic arterial chemotherapy in pediatric patients with retinoblastoma. Although the underlying mechanisms remain unclear, autonomic responses are presumed to contribute to these events. We hypothesized that periprocedural heart rate variability would differ between patients with and without events. Between April 2018 and September 2019, 38 patients (age under 7 years) were included. Heart rate variability was analyzed using electrocardiogram, and oxygen reserve index was also monitored. Cardiorespiratory events were defined as > 30% changes in blood pressure or heart rate, > 20% changes in end-tidal carbon dioxide, > 40% changes in peak inspiratory pressure, or pulse oxygen saturation < 90% during ophthalmic artery catheterization. Heart rate variability and oxygen reserve index were compared between patients with and without cardiorespiratory events. Cardiorespiratory events occurred in 13/38 (34%) patients. During the events, end-tidal carbon dioxide was significantly lower (median difference [95% CI], - 2 [- 4 to - 1] mmHg, p = 0.006) and the maximum peak inspiratory pressure was higher (30 [25-37] vs. 15 [14-16] hPa, p < 0.001), compared to patients without events. Standard deviation of normal-to-normal R-R interval, total power, and very low-frequency power domain increased during selection of the ophthalmic artery in patients with events (all adjusted p < 0.0001), without predominancy of specific autonomic nervous alterations. Oxygen reserve index was significantly lower in patients with events than those without throughout the procedure (mean difference [95% CI], - 0.19 [- 0.32 to - 0.06], p = 0.005). Enhanced compensatory autonomic regulation without specific autonomic predominancy, and reduced oxygen reserve index was observed in patients with cardiorespiratory events than in patients without events.

Intraoperative glucose variability, but not average glucose concentration, may be a risk factor for acute kidney injury after cardiac surgery: a retrospective study.

PURPOSE: Altered perioperative glycemic control may contribute to the development of renal dysfunction in cardiac surgery patients. Nevertheless, whether it is intraoperative hyperglycemia or increased glucose variability that affects postoperative outcomes is not yet clear. The aim of this study was to assess the association of intraoperative glucose concentration and variability with acute kidney injury (AKI) after cardiac surgery. METHODS: We retrospectively reviewed the electronic medical records of 3,598 patients who underwent cardiac surgery between November 1, 2006 to December 31, 2016. The time-weighted average glucose (TWAG) and coefficient of variation of glucose measurements were both used as measures of intraoperative glucose control with multivariable logistic regression to evaluate their relationship to postoperative AKI. RESULTS: The intraoperative glucose coefficient of variation was an independent risk factor for AKI after cardiac surgery (highest quartile odds ratio, 1.38; 95% confidence interval, 1.09 to 1.75; P = 0.01). Nevertheless, the intraoperative TWAG did not remain in the final multivariable model of postoperative AKI. CONCLUSION: Intraoperative glucose variability, but not the average glucose concentration itself, may be a risk factor for AKI after cardiac surgery.

RéSUMé: OBJECTIF: Un contrôle glycémique périopératoire déficient pourrait contribuer à l'apparition d'une dysfonction rénale chez les patients de chirurgie cardiaque. Toutefois, nous ne savons pas si c'est une hyperglycémie peropératoire ou l'augmentation de la variabilité glycémique qui affecte les pronostics postopératoires. L'objectif de cette étude était d'évaluer l'association entre la concentration et la variabilité glycémiques peropératoires et l'insuffisance rénale aiguë (IRA) après une chirurgie cardiaque. MéTHODE: Nous avons rétrospectivement passé en revue les dossiers médicaux électroniques de 3598 patients ayant subi une chirurgie cardiaque entre le 1er novembre 2006 et le 31 décembre 2016. La moyenne glycémique pondérée dans le temps et le coefficient de variation des mesures glycémiques ont été utilisés comme mesures de la régulation glycémique peropératoire, et la régression logistique multivariée a été utilisée pour évaluer leur relation à l'IRA postopératoire. RéSULTATS: Le coefficient de variation peropératoire de la glycémie était un facteur de risque indépendant d'IRA après une chirurgie cardiaque (rapport de cotes du quartile le plus élevé, 1,38; intervalle de confiance 95 %, 1,09 à 1,75; P = 0,01). Toutefois, la moyenne glycémique peropératoire pondérée dans le temps n'est pas demeurée dans le modèle multivarié final de l'IRA postopératoire. CONCLUSION: La variabilité peropératoire de la glycémie, et non la concentration glycémique moyenne, pourrait être un facteur de risque d'IRA après une chirurgie cardiaque.

Assessment of the Surveillance Interval at 1 Year after Curative Treatment in Hepatocellular Carcinoma: Risk Stratification.

Background/Aims: Guidelines recommend surveillance for hepatocellular carcinoma (HCC) recurrence at 3-month intervals during the first year after curative treatment and 6-month intervals thereafter in all patients. This strategy does not reflect individual risk of recurrence. We aimed to stratify risk of recurrence to optimize surveillance intervals 1 year after treatment. Methods: We retrospectively analyzed 1,316 HCC patients treated with resection/radiofrequency ablation at Barcelona Clinic Liver Cancer stage 0/A. In patients without 1-year recurrence under 3-monthly surveillance, a new model for recurrence was developed using backward elimination methods: training (n=582)/validation cohorts (n=291). Overall survival (OS) according to risk stratified by the new model was compared according to surveillance intervals: 3-monthly versus 6-monthly (n=401) after lead time bias correction and propensity-score matching analyses. Results: Among patients without 1-year recurrence, age and international normalized ratio values were significant factors for recurrence (hazard ratio [HR], 1.03; 95% confidence interval [CI], 1.00 to 1.03; p=0.009 and HR, 5.63; 95% CI, 2.24 to 14.18; p<0.001; respectively). High-risk patients stratified by the new model showed significantly higher recurrence rates than low-risk patients in the validation cohort (HR, 1.73; 95% CI, 1.18 to 2.53; p=0.005). After propensity-score matching between the 3-monthly and 6-monthly surveillance groups, OS in high-risk patients under 3-monthly surveillance was significantly higher than that under 6-monthly surveillance (p=0.04); however, OS in low-risk patients under 3-monthly surveillance was not significantly different from that under 6-monthly surveillance (p=0.17). Conclusions: In high-risk patients, 3-monthly surveillance can prolong survival compared to 6-monthly surveillance. However, in low-risk patients, 3-monthly surveillance might not be beneficial for survival compared to 6-monthly surveillance.

The effects of ipsilateral tilt position on right subclavian venous catheterization: study protocol for a prospective randomized trial.

BACKGROUND: The cross-sectional area of the subclavian vein (csSCV) is an important factor determining the success rate of SCV catheterization. The head-down position increases the csSCV. However, the effects of lateral tilting on subclavian venous cross-sectional area have not yet been explored. In this trial, we test our hypothesis that ipsilateral tilt during right SCV catheterization may significantly increase the csSCV by impeding blood flow to the heart, thereby increasing the primary venipuncture success rate and reducing the complication rate and procedure time. METHODS/DESIGN: This is a two-staged, prospective, randomized, controlled trial conducted on 237 neurosurgical patients requiring SCV catheterization. Seventeen patients in stage I will be placed in supine, 20° ipsilateral tilt, and 20° contralateral tilt positions in random order. The right csSCV will be measured using ultrasonography at each position. In stage II, 220 patients will be randomly assigned to the ipsilateral tilt group (n = 110) and supine group (n = 110) according to the position for right SCV catheterization. Data on catheterization-related characteristics and complications will be collected during and after catheterization. The primary outcome measures are the right csSCV for stage I and primary venipuncture success rate for stage II. The secondary outcome measures for stage II are time to venipuncture, total catheterization time, first-pass success rate, and complications, such as arterial puncture, hematoma, pneumothorax, air embolism, and catheter misplacement. DISCUSSION: This is the first trial to investigate the effects of the ipsilateral tilt position on right SCV catheterization. We will attest the beneficial effects of the ipsilateral tilt position on the csSCV and the primary venipuncture success rate during right SCV catheterization. Furthermore, comparisons of the first-pass success rate, complications, and total catheterization time during SCV catheterization in the ipsilateral tilt position vs. the supine position will help us determine which position is better for safe and easy SCV catheterization. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03296735 . Registered on 25 September 2017 for stage I; NCT03303274 Registered on 6 October 2017 for stage II.

Positive end-expiratory pressure-induced increase in external jugular venous pressure does not predict fluid responsiveness in laparoscopic prostatectomy.

BACKGROUND: Dynamic change in central venous pressure (CVP) was associated with fluid responsiveness. External jugular venous pressure (EJVP) may reliably estimate CVP and have the advantages of being less invasive. We investigated whether increase in EJVP induced by positive end-expiratory pressure (PEEP) could be a reliable predictor of fluid responsiveness in patients undergoing robot-assisted laparoscopic prostatectomy (RALP). METHODS: Fifty patients who underwent RALP with steep Trendelenburg position were enrolled. PEEP of 10 cmH2O was applied for 5 min and then 300 ml of colloid was administered. EJVP, stroke volume variation (SVV), and cardiac index calculated by pulse contour method were measured before and after the PEEP challenge and colloid administration. Increase in cardiac index > 10% was used to define the fluid responsiveness. RESULTS: Twenty-six patients were fluid responders. Neither the increase in EJVP after the initial PEEP nor SVV was significantly different between responders and non-responders. They were not significantly correlated with an increase in cardiac index. The areas under the receiver operating characteristic curve (AUC) of these two variables were not significantly greater than 0.5. However, a post hoc analysis revealed that AUC of a decrease in EJVP after removal of PEEP was significantly greater than 0.50. CONCLUSION: Our study results suggested that SVV and increase in EJVP after applying PEEP were not accurate predictors of fluid responsiveness during RALP. Further studies are required to find an adequate preload index in robot-assisted urologic surgery with steep Trendelenburg position.

Risk of non-cardiac surgery after percutaneous coronary intervention with drug-eluting stents.

Elective non-cardiac surgery (NCS) should optimally be delayed one year after implantation of a drug-eluting stent (DES). Dual antiplatelet therapy or at least aspirin is recommended to be continued considering the relative risk of stent thrombosis especially during the 4 weeks after DES implantation. However, these recommendations were supported by insufficient evidence. We investigated predictors for postoperative major adverse cardiovascular and cerebral event (MACCE) in 1582 patients undergoing non-cardiac surgery after DES implantation. 96 patients (6.1%) developed postoperative MACCE. In the propensity score-matched analysis, aspirin maintenance was not associated with MACCE (odds ratio [OR] 0.78, 95% confidence interval [CI] 0.48-1.27, P = 0.320) and was associated with increased risk of major bleeding (OR 1.84, 95% CI 1.02-3.32, P = 0.044). When patients who underwent NCS within one month after DES implantation were matched with those who underwent NCS thereafter, the risk of MACCE was higher when surgery was done within 30 days after PCI (OR 2.21, 95% CI 1.05-4.66, P = 0.036). Maintenance of aspirin did not decrease MACCE after NCS in patients with DES and only increased the risk of major bleeding. NCS within one month after DES implantation was associated with higher incidence of MACCE. However, prospective trials are required to validate our results.

Interaction between FEZ1 and DISC1 in regulation of neuronal development and risk for schizophrenia.

Disrupted-in Schizophrenia 1 (DISC1), a susceptibility gene for major mental disorders, encodes a scaffold protein that has a multifaceted impact on neuronal development. How DISC1 regulates different aspects of neuronal development is not well understood. Here, we show that Fasciculation and Elongation Protein Zeta-1 (FEZ1) interacts with DISC1 to synergistically regulate dendritic growth of newborn neurons in the adult mouse hippocampus, and that this pathway complements a parallel DISC1-NDEL1 interaction that regulates cell positioning and morphogenesis of newborn neurons. Furthermore, genetic association analysis of two independent cohorts of schizophrenia patients and healthy controls reveals an epistatic interaction between FEZ1 and DISC1, but not between FEZ1 and NDEL1, for risk of schizophrenia. Our findings support a model in which DISC1 regulates distinct aspects of neuronal development through its interaction with different intracellular partners and such epistasis may contribute to increased risk for schizophrenia.

Citicoline reduces upregulated clusterin following kainic acid injection in the rat retina.

PURPOSE: To investigate the effects of citicoline on upregulated clusterin and retinal damage induced by kainic acid (KA). METHODS: KA was injected into the vitreous of rats. Effects of systemic citicoline treatments were estimated by measuring the thickness of the various retinal layers, immunoblotting, and immunohistochemical techniques. RESULTS: One day after KA injection, the immunoreactivity of clusterin increased significantly. In rats treated with KA plus citicoline, clusterin immunoreactivity was markedly reduced compared to KA-treated rats. Western blot analysis showed that clusterin protein levels were increased in KA-treated rats, but decreased in KA plus citicoline-treated rats. Apoptotic cell death was determined by TUNEL method. Citicoline reduced the expression of clusterin, as well as the expression of TUNEL after KA injection in the rat retina. CONCLUSION: The increased expression of clusterin following KA injection in the rat retina suggests the presence of neurodegenerative events; citicoline may provide neuroprotection against neuronal cell damage.