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Increased carotid intima-media thickness (C-IMT), a marker of atherosclerosis, is known to be associated with cerebrovascular and cortical abnormalities and cognitive impairment. This prospective observational study investigated the association between increased C-IMT and postoperative cognitive dysfunction (POCD) in older adult patients undergoing off-pump coronary artery bypass surgery. A total of 201 patients (57 females, 144 males; >60 years) were classified into increased (n = 105) or normal (n = 96) C-IMT groups by a cut-off value of 0.9 mm (bilateral C-IMT mean). Cognitive function was serially assessed with the Korean Mini-Mental State Examination, and Korean Montreal Cognitive Assessment scores preoperatively and at 7 days and 3 months postoperatively. POCD was defined as the deterioration of 1 standard deviation in at least one of the postoperative tests compared with their corresponding baseline scores. Independent risk factors for POCD were evaluated using multivariable analysis. Overall, POCD occurred in 46 patients (23%) over the 3 months. The incidences of POCD at 7 days and 3 months after surgery were similar, and there was no difference in both Korean Mini-Mental State Examination and Korean Montreal Cognitive Assessment test scores before and after surgery between groups. Chronic obstructive lung disease and intraoperative hyperglycemia episodes (>180 mg/dL), but not increased C-IMT, were independent risk factors for POCD. Unlike in nonsurgical cohorts, increased C-IMT was not significantly associated with the occurrence of POCD in older adult patients undergoing off-pump coronary artery bypass surgery.

Ischemia-reperfusion injury is inevitable during donor organ harvest and recipient allograft reperfusion in kidney transplantation, and affects graft outcomes. Dexmedetomidine, an α2-adrenoreceptor agonist, has renoprotective effects against ischemia-reperfusion injury. We investigated the effects of intraoperative dexmedetomidine infusion on renal function and the development of delayed graft function after elective living donor kidney transplantation in a randomized controlled trial.A total of 104 patients were randomly assigned to receive either an intraoperative infusion of dexmedetomidine 0.4 μg·kgThe mean (standard deviation) serum creatinine level on POD 7 was comparable between the groups (dexmedetomidine vs control: 1.11 [0.87] mg·dLIntraoperative dexmedetomidine infusion did not produce any beneficial effects on renal function or delayed graft function in patients undergoing elective living donor kidney transplantation.www.gov (NCT03327389); registered 31 October 2017.RéSUMé: OBJECTIF: Les lésions d’ischémie-reperfusion sont inévitables lors du prélèvement d’organes du donneur et de la reperfusion de l’allogreffe chez le receveur pour une transplantation rénale, et affectent le devenir du greffon. La dexmédétomidine, un agoniste des adrénorécepteurs de type α2, a des effets néphroprotecteurs sur les lésions d’ischémie-reperfusion. Nous avons réalisé une étude randomisée contrôlée afin d’examiner les effets d’une perfusion peropératoire de dexmédétomidine sur la fonction rénale et l’apparition d’un retard de fonctionnement du greffon après une transplantation rénale élective issue de donneurs vivants. MéTHODE: Au total, 104 patients ont été aléatoirement répartis pour recevoir une perfusion peropératoire de 0,4 μg·kg

By monitoring the brain as the index organ of global oxygen supply–demand balance including major organs, regional cerebral oxygen saturation (rScO2) may indicate adequacy of renal perfusion. The aim of this study was to investigate the relationship between perioperative rScO2 and acute kidney injury (AKI) after off-pump coronary artery bypass (OPCAB). AKI was diagnosed according to the Kidney Disease: Improving Global Outcomes criteria. Collected rScO2 variables were baseline, mean, and lowest value during surgery, maximal percentage decrease from baseline, and areas under the threshold below an absolute value of 50% (AUT50) and of 80% of baseline (AUT80%base). Among 580 patients, AKI developed in 143 (24.7%) patients. Patients with AKI had lower baseline, mean, and lowest rScO2 and higher AUT50 and AUT80%base than those without AKI despite routine efforts to restore the rScO2 values within 20% of the baseline. Among the rScO2 variables, the area under the receiver operating characteristic curve of mean rScO2 was the highest (0.636), which was used for the multivariable logistic regression. Multivariable logistic regression revealed mean rScO2 as an independent predictor of AKI (odds ratio, 0.964; 95% confidence interval, 0.937–0.990; p = 0.008), along with chronic kidney disease and emergency surgery. Low intraoperative mean rScO2 was independently associated with AKI after OPCAB, which may serve as an early marker of renal injury.

When hemoglobin (Hb) is fully saturated with oxygen, the additional gain in oxygen delivery (DO2) achieved by increasing the fraction of inspired oxygen (FiO2) is often considered clinically insignificant. In this study, we evaluated the change in DO2, interrogated by mixed venous oxygen saturation (SvO2), in response to a change in FiO2 of 0.5 during cardiac surgery. When patients were hemodynamically stable, FiO2 was alternated between 0.5 and 1.0 in on-pump cardiac surgery patients (pilot study), and between 0.3 and 0.8 in off-pump coronary artery bypass grafting patients (substudy of the CARROT trial). After the patient had stabilized, a blood gas analysis was performed to measure SvO2. The observed change in SvO2 (ΔSvO2) was compared to the expected ΔSvO2 calculated using Fick’s equation. A total 106 changes in FiO2 (two changes per patient; total 53 patients; on-pump, n = 36; off-pump, n = 17) were finally analyzed. While Hb saturation remained near 100% (on-pump, 100%; off-pump, mean [SD] = 98.1% [1.5] when FiO2 was 0.3 and 99.9% [0.2] when FiO2 was 0.8), SvO2 changed significantly as FiO2 was changed (the first and second changes in on-pump, 7.7%p [3.8] and 7.6%p [3.5], respectively; off-pump, 7.9%p [4.9] and 6.2%p [3.9]; all P 2 after the FiO2 change of 0.5 was ≥ 5%p in 82 (77.4%) changes and ≥ 10%p in 31 (29.2%) changes (mean [SD], 7.5%p [3.9]). Hb concentration was not correlated with the observed ΔSvO2 (the first changes, r = − 0.06, P = 0.677; the second changes, r = − 0.21, P = 0.138). The mean (SD) residual ΔSvO2 (observed − expected ΔSvO2) was 0%p (4). Residual ΔSvO2 was more than 5%p in 14 (13.2%) changes and exceeded 10%p in 2 (1.9%) changes. Residual ΔSvO2 was greater in patients with chronic kidney disease than in those without (median [IQR], 5%p [0 to 7] vs. 0%p [− 3 to 2]; P = 0.049). DO2, interrogated by SvO2, may increase to a clinically significant degree as FiO2 is increased during cardiac surgery, and the increase of SvO2 is not related to Hb concentration. SvO2 increases more than expected in patients with chronic kidney disease. Increasing FiO2 can be used to increase DO2 during cardiac surgery.

OBJECTIVES We investigated whether routine perioperative intravenous iron replenishment reduces the requirement for packed erythrocytes (pRBC) transfusion. SUMMARY BACKGROUND DATA Patients undergoing complex cardiac surgery are at high risk of developing postoperative iron deficiency anemia, thus requiring transfusion, which is associated with adverse outcomes. METHODS Patients were randomized to receive either ferric derisomaltose 20 mg/kg (n = 103) or placebo (n = 101) twice during the perioperative period: 3 days before and after the surgery. The primary endpoint was the proportion of patients who received pRBC transfusion until postoperative day (POD) 10. Hemoglobin, reticulocyte count, serum iron profile, hepcidin, and erythropoietin were serially measured. RESULTS pRBC was transfused in 60.4% and 57.2% of patients in the control and iron group, respectively (P = 0.651). Hemoglobin concentration at 3 weeks postoperatively was higher in the iron group than in the control group (11.6 ± 1.5 g/dl vs. 10.9 ± 1.4 g/dl, P < 0.001). The iron group showed higher reticulocyte count (205 [150-267]×103/μl vs. 164 [122-207]×103/μl, P = 0.003) at POD 10. Transferrin saturation and serum ferritin were significantly increased in the iron group than in the control group (P < 0.001). Serum hepcidin was higher in the iron group than in the control group at POD 3 (106.3 [42.9-115.9] ng/ml vs. 39.3 [33.3-43.6] ng/ml, P < 0.001). Erythropoietin concentration increased postoperatively in both groups (P = 0.003), with no between-group difference. CONCLUSIONS Intravenous iron supplementation during index hospitalization for complex cardiac surgery did not minimize pRBC transfusion despite replenished iron store and augmented erythropoiesis, which may be attributed to enhanced hepcidin expression.

Ischemic and hemorrhagic complications are major determinants of survival in acute coronary syndrome (ACS) patients undergoing coronary surgery. We investigated the association of preoperative platelet reactivity to P2Y12 antagonists with ischemic and hemorrhagic complications after Off-Pump Coronary Artery Bypass surgery (OPCAB) in ACS patients who received dual anti-platelet therapy (DAPT) within 5 days prior to surgery. This prospective, observational study with 177 patients compared the incidence of perioperative major bleeding and major adverse cardiac events (MACEs) in relation to the tertile distribution of the % inhibitory response to P2Y12 antagonists, as measured by a thromboelastography platelet mapping assay. The incidences of perioperative major bleeding and MACEs were similar in relation to the tertile distribution of inhibitory response to P2Y12 antagonists. The % inhibitory responses to P2Y12 antagonists between patients who did or did not exhibit MACEs, and with or without major bleeding, were 58 ± 20% and 56 ± 20% (p = 0.578) and 57 ± 19% and 56 ± 21% (p = 0.923), respectively. In ACS patients who received DAPT close to OPCAB, the platelet inhibitory response to P2Y12 antagonists was not associated with ischemic or hemorrhagic complications. OPCAB may obviate the need for routine platelet function testing for ACS patients requiring DAPT and surgical revascularization. Clinical Registration Number: NCT02184884.

Outcomes of cardiac surgery are influenced by systemic inflammation. High mobility group box 1 (HMGB1), a pivotal inflammatory mediator, plays a potential role as a prognostic biomarker in cardiovascular disease. The aim of this prospective, observational study was to investigate the relationship between serum HMGB1 concentrations and composite of morbidity endpoints in cardiac surgery. Arterial blood samples for HMGB1 measurement were collected from 250 patients after anaesthetic induction (baseline) and 1 h after weaning from cardiopulmonary bypass (post-CPB). The incidence of composite of morbidity endpoints (death, myocardial infarction, stroke, renal failure and prolonged ventilator care) was compared in relation to the tertile distribution of serum HMGB1 concentrations. The incidence of composite of morbidity endpoints was significantly different with respect to the tertile distribution of post-CPB HMGB1 concentrations (p = 0.005) only, and not to the baseline. Multivariable analysis revealed post-CPB HMGB1 concentration (OR, 1.072; p = 0.044), pre-operative creatinine and duration of CPB as independent risk factors of adverse outcome. Accounting for its prominent role in mediating sterile inflammation and its relation to detrimental outcome, HMGB1 measured 1 h after weaning from CPB would serve as a useful biomarker for accurate risk stratification in cardiac surgical patients and may guide tailored anti-inflammatory therapy.

Background: The prognostic consequences of transient hemodynamic deterioration due to cardiac displacement, which is most severe during left circumflex artery (LCX) grafting in off-pump coronary artery bypass surgery (OPCAB) are unknown. This study aimed to investigate the association between mixed venous oxygen saturation (SvO2) < 60% during LCX grafting and the occurrence of composite of morbidity endpoints.Methods: Data of patients who underwent elective OPCAB between January 2010 and December 2019 were reviewed. Logistic regression analysis was performed to detect risk factors for the composite of morbidity endpoints, defined as 30-day or in-hospital mortality, postoperative myocardial infarction, prolonged mechanical ventilation > 24 h, cerebrovascular accident, and acute kidney injury. Results: Among 1,071 patients, the composite of morbidity endpoints occurred in 303 (28%) patients. SvO2 < 60% during LCX grafting was significantly associated with the composite of morbidity (OR: 2.72, 95% CI [1.60, 4.61], P < 0.001) along with advanced age, chronic kidney disease, ratio of early mitral inflow velocity to mitral annular early diastolic velocity, and EuroSCORE II. Other major hemodynamic variables including the cardiac index were not associated with the outcome. Additional regression analysis revealed pre-operative anemia as a predictor of SvO2 < 60% during LCX grafting (OR: 2.09, 95% CI [1.33, 3.29], P = 0.001).Conclusions: A decrease in SvO2 < 60%, albeit confined to the period of cardiac displacement, was associated with a 2.7-fold increased risk of detrimental outcomes after OPCAB, implying the prognostic importance of this transient deterioration in oxygen supply-demand balance.

While elevated hepcidin levels with inflammation have been postulated as a putative mechanism hindering effective erythropoiesis after intravenous (IV) iron therapy in anemic patients undergoing surgery, little is known about the concomitant changes in other major regulators affecting erythropoiesis. This study investigated the activities of relevant regulators after iron replenishment in a rat model of iron deficiency anemia with inflammation.Inflammation was induced by administration of complete Freund's adjuvant (CFA) in male Sprague-Dawley rats. After 2 weeks of CFA treatment, the rats received IV iron (CFA‑iron) or saline (CFA-saline). The control group received saline instead of CFA and iron (saline-saline). At 1, 3, and 10 days after iron or saline treatment, inflammatory cytokines, oxidative markers, iron profiles, hepcidin, erythropoietin (EPO), erythroferrone (ERFE), fibroblast growth factor 23 (FGF 23), and expression of mRNA and proteins in the liver involved in hepcidin signaling pathways were measured.CFA treatment and iron restriction decreased hemoglobin and serum iron levels, significantly increasing inflammatory and oxidative markers. Iron supplementation did not restore hemoglobin levels despite improved iron profiles. CFA injections increased hepcidin and FGF 23 levels and decreased EPO and ERFE levels, which further intensified after iron supplementation with concomitantly elevated levels of oxidative stress and inflammatory markers.Under inflammatory conditions, IV iron administration exacerbated inflammatory and oxidative stress and did not resolve anemia, even under iron deficiency conditions. Iron therapy exerted adverse influences on the changes in key regulators toward impeding erythropoiesis that was already impeded by inflammation.

Malnutrition is a well-recognized risk factor for poor prognosis and mortality. We investigated whether preoperative malnutrition diagnosed with objective nutritional scores affects 1-year mortality in patients undergoing valvular heart surgery.In this retrospective cohort observational study, we evaluated the association among the Controlling Nutritional Status score, Prognostic Nutritional Index, and Geriatric Nutritional Risk Index with 1-year mortality in 1927 patients undergoing valvular heart surgery. We identified factors for mortality using multivariable Cox proportional hazard analysis and investigated the utility of nutritional scores for risk stratification.Malnutrition, as identified by a high Controlling Nutritional Status score and low Prognostic Nutritional Index and Geriatric Nutritional Risk Index, was significantly associated with higher 1-year mortality. Kaplan-Meier survival curve showed that mortality significantly increased as the severity of malnutrition increased (log-rank test, P .001). The predicted discrimination (C-index) was 0.79 with the Controlling Nutritional Status score, 0.77 with the Prognostic Nutritional Index, and 0.73 with the Geriatric Nutritional Risk Index. Each nutritional index (Controlling Nutritional Status; hazard ratio, 1.31, 95% confidence interval, 1.21-1.42, P .001), the European System for Cardiac Operative Risk Evaluation II (hazard ratio, 1.07, 95% confidence interval, 1.04-1.09, P .001), and chronic kidney disease (hazard ratio, 2.26, 95% confidence interval, 1.31-3.90, P = .003) were independent risk factors for mortality. The Controlling Nutritional Status score added to the European System for Cardiac Operative Risk Evaluation II significantly increased the predictive discrimination ability for mortality (C-index 0.82, 95% confidence interval, 0.78-0.87, P = .014) compared with the Controlling Nutritional Status or European System for Cardiac Operative Risk Evaluation II alone.Preoperative malnutrition as assessed by objective nutritional scores was associated with 1-year mortality after valvular heart surgery. The Controlling Nutritional Status score had the highest predictive ability and, when added to the European System for Cardiac Operative Risk Evaluation II, provided more accurate risk stratification.

We investigated the role of echocardiographic indices consisting of left ventricular end-diastolic area (LVEDA) in combination with Doppler-derived surrogates of diastolic compliance and filling (E/E′, E′/S′, E′/A′, early transmitral flow velocity (E), tissue Doppler-derived early (E′) diastolic, late (A′) diastolic, or peak systolic (S′) velocity of the mitral annulus) in predicting fluid responsiveness in off-pump coronary surgery. Hemodynamic and echocardiographic variables were prospectively assessed under general anesthesia before and after a fluid challenge of 6 mL/kg during apnea at atmospheric pressure in 64 patients with LV ejection fraction ≥40%. Forty patients (63%) were fluid responders (≥15% increase in stroke volume index). E/E′ and E′/S′ could predict fluid responsiveness with area under the receiver operating characteristic curve (AUROC) of 0.71 (95% confidence interval [CI], 0.56–0.85, p = 0.006) and 0.68 (95% CI, 0.54–0.82, p = 0.017), respectively. The combination of LVEDA and E/E′ showed incremental predictive ability for fluid responsiveness compared with LVEDA (AUROC, 0.60, p = 0.170) or pulse pressure variation (AUROC, 0.70, p = 0.002), yielding the highest AUROC of 0.78 (95% CI, 0.66–0.90, p &lt, 0.001). The combined index of echocardiographic variables reflecting LV dimension (LVEDA) and diastolic compliance and filling (E/E′) is a potentially useful predictor of fluid responsiveness.

We examined changes in hepcidin (closely associated with anemia of chronic inflammation (ACI)) and upstream regulatory pathways after intravenous (IV) iron supplementation in an ACI animal model. ACI was induced in male Sprague-Dawley rats by intraperitoneally administering complete Freund’s adjuvant (CFA). Two weeks after starting CFA treatment, ACI rats received IV iron (CFA-iron) or vehicle (CFA-saline). Three days after IV iron treatment, iron profiles, hepcidin levels, and expression of proteins involved in the signaling pathways upstream of hepcidin transcription in the liver were measured. In CFA-treated rats, anemia with a concomitant increase in the levels of serum inflammatory cytokines and reactive oxygen species occurred. In CFA-iron rats, hemoglobin (Hb) concentration was still lower than that in control rats. In CFA-saline rats, hepatic hepcidin and ferritin levels increased compared with those in control rats and were further increased in CFA-iron rats. In CFA-saline rats, NADPH oxidase- (NOX-) 2, NOX-4, and superoxide dismutase levels in the liver were upregulated compared with those in control rats and their levels were further increased in CFA-iron rats. In CFA-saline rats, activities of the IL-6/STAT and BMP/SMAD pathways were enhanced in the liver compared with those in control rats and their levels were further increased in CFA-iron rats, whereas IL-6 expression remained unaffected after IV iron administration. In HepG2 cells, iron caused phosphorylation of STAT-3 and SMAD1/5 and knockdown of STAT-3 and SMAD1/5 using siRNAs reduced iron-induced hepcidin upregulation to levels similar to those in corresponding control cells. Renal erythropoietin expression and serum erythroferrone concentration were lower in CFA-iron rats than those in control rats. In ACI rats, IV iron supplementation did not recover Hb within three days despite an increase in hepatic ferritin levels, which might be attributable to an additional increase in hepcidin levels that was already upregulated under ACI conditions. Both STAT-3 phosphorylation and SMAD1/5 phosphorylation were associated with hepcidin upregulation after IV iron treatment, and this seems to be linked to iron-induced oxidative stress.

BACKGROUND Emerging evidence advocates the use of restrictive transfusion strategies at hemoglobin (Hb) levels of approximately 7-8 g/dL in cardiac surgeries using cardiopulmonary bypass. Yet, it is unclear whether the same thresholds can be applied to off-pump coronary bypass (OPCAB) that accompanies cardiac displacement and warm regional ischemia-reperfusion injury without the aid of a bypass machine. The aim of this study is to investigate the relationship between perioperative nadir Hb level and outcome following OPCAB.Methods and Results:Medical records of 1,360 patients were reviewed. Hb levels were serially assessed during and after surgery. The incidence of composite endpoints was 35%, which included myocardial infarction, stroke, acute kidney injury, sternal infection, reoperation, prolonged mechanical ventilation, and in-hospital mortality. The nadir Hb level was significantly lower in the morbidity group than in the non-morbidity group (8.1 [7.4-9.1] vs. 8.8 [7.9-9.8] g/dL, P

Ketamine’s inhibitory action on the N-methyl-d-aspartate receptor and anti-inflammatory effects may provide beneficial immunomodulation in cancer surgery. We investigated the effect of subanesthetic-dose ketamine as an adjunct to desflurane anesthesia on natural killer (NK) cell activity and inflammation in patients undergoing colorectal cancer surgery. A total of 100 patients were randomly assigned to a control or ketamine group. The ketamine group received a bolus of 0.25 mg·kg−1 ketamine five minutes before the start of surgery, followed by an infusion 0.05 mg·kg−1·hr−1 until the end of surgery; the control group received a similar amount of normal saline. We measured NK cell activity and proinflammatory cytokines (interleukin-6 [IL-6] and tumour necrosis factor-α [TNF-α]) before surgery and one, 24, and 48 hr after surgery. C-reactive protein (CRP) was measured before surgery and one, three, and five days after surgery. Carcinoembryonic antigen and cancer recurrence/metastasis were assessed two years after surgery. The NK cell activity was significantly decreased after surgery in both groups, but the change was not different between groups in the linear mixed model analysis (P = 0.47). Changes in IL-6, TNF-α, CRP, and carcinoembryonic antigen levels were not different between groups (P = 0.27, 0.69, 0.99, and 0.97, respectively). Cancer recurrence within 2 years after surgery was similar between groups (10% vs 8%, P = 0.62). Intraoperative low-dose ketamine administration did not convey any favourable impacts on overall postoperative NK cell activity, inflammatory responses, and prognosis in colorectal cancer surgery patients. www.clinicaltrial.gov (NCT03273231); registered 6 September 2017.

While both baseline regional cerebral oxygen saturation (rSO2) and intraoperative rSO2 decreases have prognostic importance in cardiac surgery, evidence is limited in patients who received interventions to correct rSO2 decreases. The primary aim was to examine the association between rSO2 values (both baseline rSO2 and intraoperative decrease in rSO2) with the composite of morbidity endpoints. We retrospectively analyzed 356 cardiac surgical patients having continuously recorded data of intraoperative rSO2 values. Per institutional guidelines, patients received interventions to restore the rSO2 value to &ge, 80% of the baseline value. Analyzed rSO2 variables included baseline value, and area under the threshold below an absolute value of 50% (AUT50). Their association with outcome was analyzed with multivariable logistic regression. AUT50 (odds ratio, 1.05, 95% confidence interval, 1.01&ndash, 1.08, p = 0.015) was shown to be an independent risk factor (along with age, chronic kidney disease, and cardiopulmonary bypass time) of adverse outcomes. In cardiac surgical patients who received interventions to correct decreases in rSO2, increased severity of intraoperative decrease in rSO2 as reflected by AUT below an absolute value of 50% was associated with a composite of adverse outcomes, implicating the importance of cerebral oximetry to monitor the brain as an index organ.

Indications of non-vitamin K antagonist oral anticoagulants (NOACs), consisting of two types: direct thrombin inhibitor (dabigatran) and direct factor Xa inhibitor (rivaroxaban, apixaban, and edoxaban), have expanded over the last few years. Accordingly, increasing number of patients presenting for surgery are being exposed to NOACs, despite the fact that NOACs are inevitably related to increased perioperative bleeding risk. This review article contains recent clinical evidence-based up-to-date recommendations to help set up a multidisciplinary management strategy to provide a safe perioperative milieu for patients receiving NOACs. In brief, despite the paucity of related clinical evidence, several key recommendations can be drawn based on the emerging clinical evidence, expert consensus, and predictable pharmacological properties of NOACs. In elective surgeries, it seems safe to perform high-bleeding risk surgeries 2 days after cessation of NOAC, regardless of the type of NOAC. Neuraxial anesthesia should be performed 3 days after cessation of NOACs. In both instances, dabigatran needs to be discontinued for an additional 1 or 2 days, depending on the decrease in renal function. NOACs do not require a preoperative heparin bridge therapy. Emergent or urgent surgeries should preferably be delayed for at least 12 h from the last NOAC intake (better if > 24 h). If surgery cannot be delayed, consider using specific reversal agents, which are idarucizumab for dabigatran and andexanet alfa for rivaroxaban, apixaban, and edoxaban. If these specific reversal agents are not available, consider using prothrombin complex concentrates.

Even after recovery from acute kidney injury, glomeruli remain vulnerable to further injury by way of interstitial fibrosis. This study is aimed at elucidating the effects of post ischemia-reperfusion (I/R) treatment with trimetazidine on the progression to renal fibrosis as well as short- and intermediate-term aspects. Trimetazidine 3 mg/kg or 0.9% saline was given intraperitoneally once upon reperfusion or daily thereafter for 5 d or 8 w. Renal histologic changes and related signaling proteins were assessed. After 24 h, post I/R treatment with trimetazidine significantly reduced serum blood urea nitrogen and creatinine levels and tubular injury accompanied with upregulation of hypoxia-inducible factor- (HIF-) 1α, vascular endothelial growth factor (VEGF), and Bcl-2 expression. After 5 d, post I/R treatment with trimetazidine reduced renal tubular cell necrosis and apoptosis with upregulation of HIF-1α-VEGF and tissue inhibitors of metalloproteinase activities, attenuation of matrix metalloproteinase activities, and alteration of the ratio of Bax to Bcl-2 levels. After 8 w, however, post I/R treatment with trimetazidine did not modify the progression of renal fibrosis. In conclusion, post I/R treatment with trimetazidine allows ischemic kidneys to regain renal function and structure more rapidly compared to nontreated kidneys, but not enough to resolute renal fibrosis in long-term aspect.

Carotid intima-media thickness (IMT) is a well-known predictor of adverse outcomes in the ischemic heart disease patients; however, evidence is lacking in patients undergoing off-pump coronary artery bypass surgery (OPCAB). Data from 407 patients who underwent OPCAB between April 2013 and August 2016 were retrospectively reviewed. A composite of cardiovascular morbidity endpoints was defined as the presence of stroke, acute myocardial infarction, new cardiac arrhythmia (newly developed atrial fibrillation, atrial flutter, or atrioventricular block), cardiovascular death, or cerebrovascular death within 30 days after surgery. Increased carotid IMT was defined as ≥0.9 mm on one or both sides. The incidence of a composite of cardiovascular morbidity endpoints was 24.0% in the normal IMT group (n = 221) and 34.4% in the increased IMT group (n = 186) (p = 0.021). Multivariable analysis revealed increased IMT (odds ratio 1.719, 95% confidence interval 1.108 to 2.666, p = 0.016) and preoperative renal replacement therapy (odds ratio 4.264, 95% confidence interval 1.679 to 10.829, p = 0.002) as independent predictors of a composite of cardiovascular morbidity endpoints. In patients undergoing OPCAB, preoperative assessment of carotid IMT may help predicting the development of a postoperative composite of cardiovascular morbidity endpoints.

Bisphenol A (BPA) is a well-known endocrine-disrupting chemical related to the carcinogenesis of estrogen-responsive organs. Although human exposure to BPA mainly occurs via the oral route, its association with colon cancer has not been fully elucidated. We investigated the effects of BPA on the proliferation, migration, and tumor growth of colon cancer cells. BPA significantly promoted the proliferation of HT-29 human colon adenocarcinoma cells in a time- and dose-dependent manner. BPA also increased HT-29 cells migration. BPA increased the phosphorylation of extracellular signal-regulated kinase (ERK), and inhibition of the ERK pathway attenuated BPA-induced proliferation and migration. In addition, BPA reduced E-cadherin expression, a key factor impeding epithelial-to-mesenchymal transition, and increased 5-HT3 receptors expression, a major mitogenic factor. In xenograft models, tumor volume of the BPA-treated nude mice was 4.6 times that of the saline-treated group. Our findings provide primary evidence regarding the link between BPA and human colon cancer by demonstrating that BPA promotes the proliferation, migration, and tumor growth of colon cancer cells in both in vitro and in vivo models. In addition, we provided the mechanism of action of BPA, involved in the activation of the ERK pathway, the decrease in E-cadherin, and the increase in 5-HT3 receptors.

Background Hyperglycemia (HG) exacerbates myocardial ischemia/reperfusion (I/R) injury and renders protective strategies ineffective by amplified inflammatory response via enhanced high-mobility group box-1 (HMGB1) release. This study investigated the role of ethyl pyruvate (EP) against myocardial I/R injury under a clinically relevant HG condition. Methods Sprague-Dawley rats (n=76) were randomly assigned to 6 groups: normoglycemia (NG)-Sham, NG-I/R-control (C, saline), NG-I/R-EP treatment (50mg/kg) upon reperfusion, HG-Sham, HG-I/R-C, and HG-I/R-EP treatment upon reperfusion. HG was induced by 1.2g/kg dextrose. I/R was induced by ligation of the left anterior descending artery for 30min followed by 4h of reperfusion. Results HG resulted in exacerbation of myocardial infarct size by 19% with amplified activation of HMGB1–receptors of advanced glycation end products/toll like receptors–NF-κB pathway compared to NG following I/R, which all could be attenuated by EP. EP treatment was associated with diminished tumor necrosis factor-α, interleukin-1β, and interleukin-6 expressions. It also served to normalize the increase in pro-apoptotic Bax and the decrease in anti-apoptotic Bcl-2 protein levels. These effects were associated with decreased myocardial apoptosis and infarct size (by 30% and 36% in the NG and HG groups, respectively) regardless of the glycemic condition. Conclusion HG exacerbated myocardial I/R injury through amplified inflammatory response via increased HMGB1 level. EP treatment upon reperfusion conveyed significant myocardial protection against the I/R injury under both NG and HG conditions. Common to both glycemic conditions, associated mechanisms involved attenuated increase in HMGB1 level and suppression of its down-stream pathways.

Perioperative cerebral hypoperfusion/ischemia is a major inciting factor of postoperative delirium, which is coupled with adverse outcome in elderly patients. Cerebral oximetry enables noninvasive assessment of the regional cerebral oxygen saturation (rSO2). This study aimed to investigate whether perioperative rSO2 variations were linked to delirium in elderly patients after spinal surgery.Postoperative delirium was assessed for 48 hours postsurgery in 109 patients aged over 60 years without a prior history of cerebrovascular or psychiatric diseases by the Confusion Assessment Method for the intensive care unit and the intensive care delirium screening checklist. The rSO2 values immediately before and throughout surgery were acquired. The preoperative cognitive functions, patient characteristics, and perioperative data were recorded.During the 48-h postoperative period, 9 patients (8%) exhibited delirium. The patients with delirium showed similar perioperative rSO2 values as those without, in terms of the median lowest rSO2 values (55% vs. 56%; P=0.876) and incidence (22%, both) and duration of decline of rSO280% of the baseline values. The serially assessed hemodynamic variables, hematocrit levels, and blood gas analysis variables were also similar between the groups, except for the number of hypotensive events per patient, which was higher in the patients with delirium than in those without (4, interquartile range [IQR] 3 to 6 vs. 2, IQR: 1to 3; P=0.014).The degree and duration of decrease of the perioperative rSO2 measurements were not associated with delirium in elderly patients after spinal surgery.

Background Acute kidney injury (AKI) is a frequent and serious complication after aortic surgery requiring cardiopulmonary bypass (CPB). Dexmedetomidine, a selective α-2 adrenoreceptor agonist, may reduce AKI because of its sympatholytic and anti-inflammatory effects against ischaemia–reperfusion injury. We investigated the effect of dexmedetomidine administration on AKI after aortic surgery requiring CPB in a placebo-controlled randomised controlled trial. Methods A total of 108 patients were randomly assigned to an infusion of dexmedetomidine or saline at a rate of 0.4 μg kg−1 h−1 for 24 h starting after anaesthetic induction. The primary outcome was the incidence of AKI, as defined by the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. The secondary outcomes included delirium and major morbidity. Safety outcomes were drug-related adverse events (bradycardia, hypotension). Results AKI occurred in 7/54 (13%) subjects randomised to dexmedetomidine, compared with 17/54 (31%) subjects randomised to saline infusion (odds ratio=0.32; 95% confidence interval [CI], 0.12–0.86; P=0.026). Secondary outcomes, including stroke, mortality, and delirium, were similar between subjects randomised to dexmedetomidine (16/54 [30%] or saline control (22 [41%]; odds ratio=0.61 [95% CI, 0.28–1.36]). The incidence of bradycardia and hypotension was similar between groups (14/54 (26%) vs. 17/54 (32%) (odds ratio:0.76 (95%CI:0.33–1.76) and 29/54 (54%) vs. 36/54 (67%) (odds ratio:0.58 (95%CI:0.27–1.26), respectively). The length of hospital stay was shorter in the dexmedetomidine group (12 [10–17] days) vs saline control (15 [11–21] days; P=0.039). Conclusions Pre-emptive dexmedetomidine administration for 24 h starting after induction of anaesthesia reduced the incidence of AKI after aortic surgery requiring CPB, without any untoward side-effects related to its sedative or sympatholytic effects. Clinical trial registration NCT02607163 (www.ClinicalTrials.gov).

Delirium is a frequent and serious complication after cardiac surgery with cerebral hypoperfusion as one from the key pathophysiological mechanisms. Middle cerebral artery (MCA) mean blood flow velocity (MFV) measured by transcranial Doppler has been used as a marker of cerebral perfusion, and cerebral oximetry (rSO2) value as a marker of its adequacy. This prospective observational trial examined the predictive value of MCA MFV and rSO2, measured immediately before induction of anesthesia, for delirium after valvular heart surgery in elderly patients. In 113 patients, delirium was evaluated for 7 days postoperatively, using the confusion assessment method for the intensive care unit. The primary endpoint was the occurrence of postoperative delirium. Overall, 16 patients (14%) exhibited delirium. MCA MVF values could not predict the development of delirium. Preoperative statin use, geriatric depression scale score, and low preoperative rSO2 (

Acute kidney injury (AKI) is a common morbidity after off-pump coronary revascularization. We investigated whether perioperative administration of sodium bicarbonate, which might reduce renal injury by alleviating oxidative stress in renal tubules, prevents postoperative AKI in off-pump coronary revascularization patients having renal risk factors.Patients (n=162) having at least one of the following AKI risk factors were enrolled: (i) age70 yr; (ii) diabetes mellitus; (iii) chronic renal disease; (iv) congestive heart failure or left ventricular ejection fraction35%; and (v) reoperation or emergency. Patients were evenly randomized to receive either sodium bicarbonate (0.5 mmol kgThe incidences of AKI were 21 and 26% in the bicarbonate and control groups, respectively (P=0.458). Serially measured serum creatinine concentrations and perioperative fluid balance were also comparable between the groups. The length of postoperative hospitalization and incidence of morbidity end points were similar between the groups, whereas significantly more patients in the bicarbonate group required prolonged mechanical ventilation (24 h) relative to the control group (20 vs 6, P=0.003).Perioperative sodium bicarbonate administration did not decrease the incidence of AKI after off-pump coronary revascularization in high-risk patients and might even be associated with a need for prolonged ventilatory care.NCT01840241.

Background This randomized trial evaluated the effect of intravenous patient-controlled analgesia (IV-PCA) based on fentanyl mixed with either propacetamol or an equivalent volume of normal saline on postoperative nausea and vomiting (PONV) in highly susceptible patients undergoing spinal surgery. Materials and methods One hundred eight nonsmoking female patients were randomly and evenly allocated to receive IV-PCA with either propacetamol (4 g) or normal saline mixed to fentanyl (20 μg/kg). Primary study outcome was PONV incidence at 24 hours postsurgery. Secondary outcomes were nausea severity, pain intensity (100-mm visual analog scale), use of rescue antiemetics and analgesics, patient satisfaction, and adverse events at 6, 12, and 24 hours postsurgery. Results Postsurgery, the propacetamol versus normal saline group had lower PONV incidence at 24 hours (41% vs. 66%, P=0.011); pain intensity at rest and rescue analgesic requirements at 6 to 12 hours (30±15 vs. 41±19, P=0.008; and 25% vs. 49%, P=0.036, respectively) and at 12 to 24 hours (25±15 vs. 35±17, P=0.008; and 19% vs. 42%, P=0.044, respectively); and higher patient satisfaction score (6.4±1.4 vs. 5.7±1.8, P=0.028). Conclusions In patients undergoing spinal surgery and at risk of developing PONV, continuous IV-PCA based on propacetamol mixed to fentanyl, relative to fentanyl alone, effectively reduced the incidence of PONV, pain intensity at rest, and additional use of rescue analgesics with higher patient satisfaction.

BACKGROUND:In this study, we examined the relationship between postoperative cognitive dysfunction (POCD) and intraoperative regional cerebral oxygen saturation (rSO2) in elderly patients undergoing spinal surgery.METHODS:We enrolled 87 patients older than 65 years. All patients were tested using a

Statins, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have the potential to reduce acute kidney injury (AKI) after cardiac surgery through their pleiotropic properties. Here we studied the preventive effect of atorvastatin on AKI after valvular heart surgery. Two-hundred statin-naive patients were randomly allocated to receive either statin or placebo. Atorvastatin was administered orally to the statin group according to a dosage schedule (80 mg single dose on the evening prior to surgery; 40 mg on the morning of surgery; three further doses of 40 mg on the evenings of postoperative days 0, 1, and 2). AKI incidence was assessed during the first 48 postoperative hours on the basis of Acute Kidney Injury Network criteria. The incidence of AKI was similar in the statin and control groups (21 vs. 26 %, respectively, p = 0.404). Biomarkers of renal injury including plasma neutrophil gelatinase-associated lipocalin and interleukin-18 were also similar between the groups. The statin group required significantly less norepinephrine and vasopressin during surgery, and fewer patients in the statin group required vasopressin. There were no significant differences in postoperative outcomes. Acute perioperative statin treatment was not associated with a lower incidence of AKI or improved clinical outcome in patients undergoing valvular heart surgery. (ClinicalTrials.gov NCT01909739).

Acute kidney injury (AKI) following cardiac surgery is closely interrelated with hemodynamic instability and sympathetic activity, and adversely influences prognosis. Here, we investigated in a randomized placebo-controlled trial whether dexmedetomidine, an α2 adrenoreceptor agonist, could prevent AKI after valvular heart surgery. Two hundred patients undergoing valvular heart surgery were randomly assigned to equal placebo or treatment groups. Dexmedetomidine was infused at a rate of 0.4 μg/kg/h starting immediately after anesthetic induction and continuing for 24 h after surgery. We then assessed the incidence of AKI during the first 48 postoperative hours, hemodynamic variables, and a composite of major morbidity end points. The incidence of AKI, based on Acute Kidney Injury Network criteria, was significantly lower in the treatment group compared with the control group (14 vs. 33%). The dexmedetomidine group exhibited a significantly lower incidence of a composite of major morbidity end points (21 vs. 38%) and a significantly shorter length of intensive care unit stay (3 [2, 3] days vs. 3 [2, 4] days) compared with the control group. Thus, perioperative infusion of dexmedetomidine effectively reduced both the incidence and severity of AKI, and improved outcome in patients undergoing valvular heart surgery without untoward hemodynamic side effects.

Positive end-expiratory pressure (PEEP)-induced increase in central venous pressure (CVP) has been suggested to be a robust indicator of fluid responsiveness, with heart rhythm having minimal influence. We compared the ability of PEEP-induced changes in CVP with passive leg raising (PLR)-induced changes in stroke volume index (SVI) in patients with atrial fibrillation after valvular heart surgery.In 43 patients with atrial fibrillation after cardiac surgery, PEEP was increased from 0 to 10 cm H2O for 5 min and changes in CVP were assessed. After returning the PEEP to 0 cm H2O, PLR was performed for 5 min and changes in SVI were recorded. Finally, 300 ml of colloid was infused and haemodynamic variables were assessed 5 min after completion of a fluid challenge. Fluid responsiveness was defined as an increase in SVI ≥10% measured by a pulmonary artery catheter.Fifteen (35%) patients were fluid responders. There was no correlation between PEEP-induced increases in CVP and changes in SVI after a fluid challenge (β coefficient -0.052, P=0.740), whereas changes in SVI during PLR showed a significant correlation (β coefficient 0.713, P0.001). The area under the receiver operating characteristic curve of the PEEP-induced increase in CVP and changes in SVI during PLR for fluid responsiveness was 0.556 [95% confidence interval (CI) 0.358-0.753, P=0.549) and 0.771 (95% CI 0.619-0.924, P=0.004), respectively.A PEEP-induced increase in CVP did not predict fluid responsiveness in patients with atrial fibrillation after cardiac surgery, but increases in SVI during PLR seem to be a valid predictor of fluid responsiveness in this subset of patients.

The association between acute kidney injury (AKI) and chronic kidney disease (CKD) remains elusive in cardiac surgery. We investigated the association between postoperative AKI and CKD development, emphasizing the intermediary role of acute kidney disease (AKD), in patients undergoing valvular heart surgery.We assessed the occurrence of postoperative AKI (7 days postsurgery), AKD (3 months postsurgery), and CKD (12 months postsurgery) in 1386 patients. The primary outcome was the development of AKD and CKD according to AKI occurrence. Relevant risk factors of AKI, AKD, and CKD were identified through multivariable regression analysis.AKI occurred in 23.9% of patients with normal preoperative renal function. Even with early recovery of renal function within 3 days, AKI increased the risk of AKD (odds ratio [OR], 3.21; 95% confidence interval [CI], 1.98-5.20, P .001) and CKD (OR, 2.86; 95% CI, 1.68-4.86, P .001), whereas persistent AKI further increased the risk of AKD (OR, 12.07; 95% CI, 5.56-26.21, P .001) and CKD (OR, 10.54; 95% CI, 4.01-27.76, P .001). We also found these relationships in patients with pre-existing renal dysfunction. Multivariable analysis identified 3-month postoperative heart failure and high right ventricular systolic pressure as independent risk factors for CKD.Even after early recovery, postvalvular heart surgery AKI was associated with increased risk of CKD via AKD in a graded manner related to AKI severity and persistence. Postoperative cardiac dysfunction assessed 3 months postsurgery also significantly influenced CKD development, indicating a need for close follow-up of cardiac and renal function to improve patient outcomes.