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Myung Il Bae, Jae-Kwang Shim, Jong Wook Song, Seo Hee Ko, Young Seo Choi, Young-Lan Kwak Department of Anesthesiology and Pain Medicine, Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul, Republic of KoreaCorrespondence: Young-Lan Kwak, Department of Anesthesiology and Pain Medicine, Anesthesia and Pain Research Institute, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea, Tel +82-2-2228-8513, Fax +82-2-2227-8063, Email YLKWAK@yuhs.acPurpose: The neutrophil-to-lymphocyte ratio (NLR) is an extensively analyzed prognostic inflammatory index in cardiac patients. The degree of change in NLR values before and after surgery (delta-NLR) can represent the inflammatory response induced by surgery and serve as a meaningful prognostic biomarker in surgical patients; however, this has not been well investigated. We aimed to investigate the predictive value of the perioperative NLR and delta-NLR for outcomes of off-pump coronary artery bypass (OPCAB) surgery by evaluating “days alive and out of hospital (DAOH)”, a novel patient-centered outcome.Patients and Methods: In this single-center retrospective study, perioperative data, including NLR data, from 1322 patients were analyzed. The primary endpoint was DOAH at 90 days postoperatively (DAOH 90), and the secondary endpoint was long-term mortality. Linear regression analysis and Cox regression analysis were performed to identify independent risk factors for the endpoints. In addition, Kaplan–Meier survival curves were plotted to assess long-term mortality.Results: The median NLR values significantly increased from 2.2 (1.6– 3.1) at baseline to 7.4 (5.4– 10.3) postoperatively, with median delta-NLR values of 5.0 (3.2– 7.6). Preoperative NLR and delta-NLR were independent risk factors for short DAOH 90 in the linear regression analysis. In Cox regression analysis, delta-NLR, but not preoperative NLR, was an independent risk factor for long-term mortality. When patients were divided into two groups according to delta-NLR, the high delta-NLR group had a shorter DAOH 90 than the low delta-NLR group. Kaplan–Meier curves showed higher long-term mortality in the high delta-NLR group than in the low delta-NLR group.Conclusion: In OPCAB patients, preoperative NLR and delta-NLR were significantly associated with DAOH 90, and delta-NLR was an independent risk factor for long-term mortality, indicating their role in risk assessment, which is essential for perioperative management.Keywords: neutrophil-to-lymphocyte ratio, off-pump coronary artery bypass, days alive and out of hospital

This study was performed to test if hearing a recorded maternal voice reduces anxiety, emergence agitation and anaesthetic requirements in children. With written informed consent, children scheduled for cardiac catheterisation under intravenous ketamine anaesthesia and their mothers (n = 46) were randomly assigned to either the mother-voice (MV) or control group. While the MV group (n = 23) listened via headphones to a recording of their mothers' voices during the perioperative period, the control group (n = 23) wore headphones with no auditory stimulation. Ketamine requirements and haemodynamics were recorded. Anxiety of the patients and the parents were measured before and after the procedure with the modified Yale preoperative anxiety scale and Spielberger's State-Trait Anxiety Inventory, respectively. Emergence agitation was graded. The demographic and haemodynamic data were comparable, except for a longer procedure time in the MV group. Mothers' State-Trait Anxiety Inventory was not different preoperatively between the groups. Mothers' state and trait anxiety was lower after the procedure in the MV group compared with the preoperative values. In the control group only maternal state anxiety was diminished after the procedure. There was no significant group difference with respect to ketamine requirement (5.1 +/- 1.9 mg vs 4.9 +/- 1.6 mg, P = 0.645). The anxiety score of children was lower in the MV group before the procedure (modified Yale preoperative anxiety scale score 35 +/- 12 vs 28 +/- 9, P = 0.038), but there was no significant difference postoperatively. Emergence agitation was attenuated in the MV group (P = 0.005). [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to determine the optimal bolus dose of alfentanil required to provide successful intubating conditions following inhalation induction of anaesthesia using 5% sevoflurane and 60% nitrous oxide without neuromuscular blockade in adult day-case anaesthesia. Methods: Twenty-four adults, aged 18–60 years, undergoing general anaesthesia for short ambulatory surgery were enroled into the study. After vital capacity induction, with sevoflurane 5% and 60% nitrous oxide in oxygen, pre-determined dose of alfentanil was injected over 30 s. The dose of alfentanil was determined by modified Dixon's up-and-down method (2 μg/kg as a step size). Ninety seconds after the end of bolus administration of alfentanil, the trachea was intubated. Systolic blood pressure, heart rate and SpO2 were recorded at anaesthetic induction, before, 1 min and 3 min after intubation. Results: The bolus dose of alfentanil for successful tracheal intubation was 10.7±2.1 μg/kg in 50% of patients during inhalation induction. From probit analysis, 50% effective dose (ED50) and ED95 values (95% confidence limits) of alfentanil were 10.7 μg/kg (8.0–12.9 μg/kg) and 14.9 μg/kg (12.9–31.1 μg/kg), respectively. Conclusions: Using the modified Dixon's up-and-down method, the bolus dose of alfentanil for successful tracheal intubation was 10.7±2.1 μg/kg in 50% of adult patients during inhalation induction using 5% sevoflurane and 60% nitrous oxide in oxygen without neuromuscular blocking agent in day-case anaesthesia. [ABSTRACT FROM AUTHOR]

Background: The aim of this randomized and controlled trial was to investigate the effect of a glucose-insulin-potassium (GIK) solution on myocardial protection in acute coronary syndrome (ACS) patients undergoing urgent multivessel off-pump coronary artery bypass (OPCAB) surgery.Methods: Sixty-six patients were randomly allocated either to receive 0.3 ml kg(-1) h(-2) GIK solution (potassium 80 mEq and regular insulin 325 IU in 500 ml of 50% glucose) or equivalent volume of normal saline (control) upon anaesthetic induction until 6 h after reperfusion. The primary endpoints were to compare the concentrations of creatine kinase-MB (CK-MB) and troponin-T between the groups after reperfusion. The secondary endpoints were to compare the incidences of postoperative troponin-T >0.8 ng ml(-1) and myocardial infarction (MI) between the groups.Results: Highest CK-MB [8.7 (4.4) vs 13.1 (7.9) ng ml(-1), P=0.006] and troponin-T [0.20 (0.13-0.49) vs 0.48 (0.18-0.91) ng ml(-1), P<0.0001] values after reperfusion were significantly lower in the GIK group compared with the control group. The area under the curve of serially measured troponin-T was also significantly smaller in the GIK group compared with the control group [0.83 (0.43-1.81) vs 0.46 (0.31-1.00), P=0.036]. Significantly fewer patients in the GIK group showed troponin-T >0.8 ng ml(-1) after reperfusion compared with the control group (3 vs 11, P=0.033). The incidence of postoperative MI was similar between the groups.Conclusions: GIK administration in ACS patients undergoing urgent multivessel OPCAB significantly attenuated the degree of ensuing myocardial injury without complications related to glycaemic control. Clinical Trial Registry. URL: http://clinicaltrials.gov/ct2/show/NCT01384656?term=GIK+AND+OPCAB&rank=1. Unique identification number NCT01384656. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the association of comprehensive geriatric assessment (related to diverse aspects of frailty) with postoperative recovery as measured by days alive and out of the hospital at 30 days (DAOH30) in older patients undergoing cardiac surgery., Design: Retrospective observational study using data retrieved from a prospective registry., Setting: Single tertiary hospital in South Korea., Participants: A total of 437 patients aged ≥65 years who underwent cardiac surgery between March 2021 and October 2022 were included., Measurements: Comprehensive geriatric assessment included subjective evaluations of functional frailty (cognitive, emotional, and physical aspects) and objective measurements of malnutrition and anaemia. DAOH30 was analysed using multivariable quantile regression to evaluate its association with these three domains., Results: In the entire cohort (median age 72 years; median DAOH30, 19 days), 85.1% of participants had functional frailty, 9.8% had malnutrition, and 45.8% had anaemia. Older age, cognitive dysfunction, emotional dysregulation, physical decline, malnutrition, and anaemia were associated with shorter DAOH30 (all p < 0.05). In multivariable analysis, malnutrition had the strongest impact, reducing DAOH30 by 6.0 days (95% confidence interval [CI]: -11.103 to -0.263), followed by anaemia (1.2 days, 95% CI: -2.199 to -0.148) and functional frailty (1.0 days, 95% CI: -1.677 to -0.171). Individual components of functional frailty did not retain an independently significant relationship with DAOH30 after adjustment for confounders., Conclusion: Comprehensive geriatric assessment, incorporating functional frailty, malnutrition, and anaemia, demonstrated a significant association with DAOH30 in older patients undergoing cardiac surgery. Among the assessed aspects, malnutrition showed the strongest association, which may underscore the importance of targeted nutritional interventions to improve outcomes in this patient population., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2025. Published by Elsevier Masson SAS.)

Objectives: To investigate the value of body composition indices derived from pre-procedural computed tomography (CT) in predicting 1-year mortality among patients who underwent transcatheter aortic valve replacement (TAVR)., Materials and Methods: We assessed consecutive patients who underwent TAVR between June 2016 and December 2021 at a single academic medical center. Skeletal muscle and subcutaneous fat area at the T4, T12, and L3 levels on pre-procedural CT were measured. The association between body composition and 1-year mortality was evaluated using Cox proportional hazard regression analysis., Results: Finally, 408 patients were included (185 men and 223 women; mean age, 81.7 ± 5.1 years; range, 62-98 years). Post-procedural death occurred in 13.2% of patients. The muscle-height index and fat-height index at the L3 level were more strongly correlated with those at the T12 level (r = 0.765, p < 0.001 and r = 0.932, p < 0.001, respectively) than with those at the T4 level (r = 0.535, p < 0.001 and r = 0.895, p < 0.001, respectively). The cumulative 1-year mortality rate was highest for patients with both sarcopenia and adipopenia (26%), followed by those with adipopenia only (17%), those with sarcopenia only (12%), and those with neither sarcopenia nor adipopenia (8%, p = 0.002). Multivariable analysis revealed that body composition at the T12 level was an independent risk factor for 1-year mortality (hazard ratio: 4.09, 95% confidence interval: 2.01-8.35) in patients with both sarcopenia and adipopenia (p < 0.001)., Conclusion: Sarcopenia or adipopenia assessed with CT at the thoracic level may be valuable for stratifying 1-year all-cause mortality in patients who undergo TAVR., Clinical Relevance Statement: Skeletal muscle and subcutaneous fat mass indices at the level of T12, measured on pre-procedural CT, have value for risk stratification of 1-year all-cause mortality in patients who undergo transcatheter aortic valve replacement., Key Points: Sarcopenia and adipopenia are associated with the prognosis of patients undergoing transcatheter aortic valve replacement. Body composition at the T12 level was an independent risk factor for 1-year all-cause mortality. Sarcopenia or adipopenia assessed at T12 with pre-procedural CT is valuable for risk stratification., Competing Interests: Compliance with ethical standards. Guarantor: The scientific guarantor of this publication is Y.J.K. Conflict of interest: The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article. Statistics and biometry: One of the authors (Mr. Yun Ho Roh) has significant statistical expertise. Informed consent: Written informed consent was waived by the Institutional Review Board. Ethical approval: Institutional Review Board approval was obtained. Study subjects or cohorts overlap: No study subjects have been previously reported. Methodology: Diagnostic or prognostic study Performed at one institution, (© 2024. The Author(s), under exclusive licence to European Society of Radiology.)

Background: Ischemia-reperfusion (I/R) injury is inevitable during the perioperative period. The pancreas is susceptible to I/R injury. Autophagy, a self-digestion process, is upregulated during I/R injury and strongly induced by hypoxia. This study aims to determine whether dexmedetomidine can decrease pancreatic β-cell damage by regulating autophagy under hypoxia., Methods: INS-1 rat insulinoma cells were cultured in dexmedetomidine before being exposed to cobalt chloride (CoCl2)-induced hypoxia. Cell viability and the expression of autophagy-related proteins (light chain 3B [LC3B]-II, p62, and ATGs) were assessed. The expression of apoptosis-related proteins (BCL-2 and P-BAD) were also evaluated. CoCl2-treated INS-1 cells were pretreated with the autophagosome formation inhibitor, 3-methyladenine (3-MA), to compare its effects with those of dexmedetomidine. Bafilomycin-A1 (Baf-A1) that inhibits autophagosome degradation was used to confirm the changes in autophagosome formation induced by dexmedetomidine., Results: Dexmedetomidine attenuated the increased expression of autophagic proteins (LC3B-II, p62, and ATGs) and reversed the CoCl2-induced reduction in the proliferation of INS-1 cells after hypoxia. Dexmedetomidine also alleviated the decreased expression of the anti-apoptotic protein (BCL-2) and the increased expression of apoptotic protein (BAX). Dexmedetomidine reduces the activation of autophagy through inhibiting autophagosome formation, as confirmed by a decrease in LC3B-II/I ratio, a marker of autophagosome formation, in LC3B turnover assay combined with Baf-A1., Conclusions: Dexmedetomidine alleviates the degree of cellular damage in INS-1 cells against CoCl2-induced hypoxia by regulating autophagosome formation. These results provide a basis for further studies to confirm these effects in clinical practice.

Background: Acute renal dysfunction is defined by the maximum increase in serum creatinine (sCr) without considering the pattern of change in sCr. We aimed to identify longitudinal patterns (trajectories) of postoperative sCr concentrations and investigate their association with long-term outcomes in patients undergoing valvular heart surgery., Materials and Methods: In this retrospective review of 3436 patients who underwent valvular heart surgery, we applied trajectory projection cluster analysis to identify the trajectories of sCr changes from baseline during the 7 postoperative days. Primary and secondary endpoints were to investigate the associations of sCr trajectories with mortality using Kaplan-Meier curves and Cox proportional hazards regression analysis and a composite of major adverse kidney events (MAKEs) at 1 year after surgery, respectively., Results: Four clusters were identified: Clusters 1 and 2, a minimal change in sCr (90.1% of patients); Cluster 3, a significant and persistent increase in sCr (4.1% of patients); and Cluster 4, a significant but transient increase in sCr (5.8% of patients). The 1-year postoperative mortality rate was higher in Cluster 3 (18.4%) and Cluster 4 (11.6%) than in Cluster 1+2 (2.7%). The Kaplan-Meier survival curve demonstrated significant differences in mortality rates among the clusters (log-rank test, P <0.001). In the multivariable Cox analysis, the sCr trajectory cluster was an independent prognostic factor for mortality. Cluster 3 had a higher prevalence of MAKEs (37.6%) compared with Cluster 1+2 (6.8%, P <0.001) and Cluster 4 (24.1%, P =0.045). The cluster was an independent prognostic factor for MAKEs., Conclusion: The sCr trajectory clusters exhibited significantly different risks of mortality and MAKEs 1 year after surgery. Through these sCr trajectories, we confirmed that both the extent of sCr increase and its sustainability during the first 7 postoperative days were closely associated with the long-term prognosis after valvular heart surgery., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Patients undergoing cardiac surgery for infective endocarditis (IE) are at a high risk of postoperative acute kidney injury (AKI) owing to heightened systemic inflammation. Therefore, we aimed to investigate the effect of dexmedetomidine on postoperative AKI in patients who underwent cardiac surgery for IE., Methods: A total of 63 patients who underwent cardiac surgery for IE were randomly assigned to receive either intravenous dexmedetomidine infusion of 0.4 μg kg -1  h -1 (DEX group) or normal saline infusion (control group) for 24 h after induction of anesthesia. The occurrence of AKI within seven days postoperation, epinephrine, norepinephrine, and interleukin-6 levels, as well as postoperative morbidities, were assessed. An intertrim analysis was conducted using Pocock's alpha spending function at α = 0.05 and β = 0.2., Results: This trial was early terminated according to the results of interim analysis performed when 60 % of the pre-set number of patients have been collected. The incidence of AKI was significantly lower in the DEX group than in the control group (32.3 % vs. 9.4 %, p = 0.025). Patients in the DEX group had significantly lower epinephrine levels than those in the control group, whereas norepinephrine and interleukin-6 levels were similar. Perioperative mean arterial pressure or heart rate did not differ between the groups., Conclusions: Dexmedetomidine administration for 24 h starting from induction of anesthesia significantly reduced the incidence of postoperative AKI after cardiac surgery for IE (by 29 % vs. control) without hemodynamic side effects. This was accompanied by a significant attenuation of postoperative increase in serum epinephrine levels., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Asian Surgical Association and Taiwan Society of Coloproctology. Published by Elsevier B.V. All rights reserved.)

The Controlling Nutritional Status (CONUT) score is a novel nutritional index that integrates the serum albumin level, peripheral blood lymphocyte count, and total cholesterol level. This retrospective study explores its prognostic significance in patients undergoing cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). We included 436 patients who underwent CRS-HIPEC, categorized into low (0-3) and high (4-12) CONUT score groups, and performed logistic regression analysis to predict one-year mortality and postoperative morbidity. Our findings revealed that high CONUT scores correlate with increased one-year mortality (47.1% vs. 20.3%, p < 0.001) and morbidity (39.2% vs. 18.2%, p < 0.001) compared to low CONUT scores. Multivariable regression analysis confirmed high CONUT scores as independent predictors of one-year mortality (odds ratio: 2.253, 95% CI: 1.014-5.005, p = 0.046) and postoperative morbidity (odds ratio: 2.201, 95% CI: 1.066-4.547, p = 0.033). These results underscore the CONUT score's effectiveness as an independent marker for evaluating risks associated with CRS-HIPEC, emphasizing its potential to improve risk stratification.

This study aimed to investigate the association between acute kidney injury (AKI) recovery subtypes and days alive out of hospital within the first 3 months (DAOH-90) in patients undergoing lung transplantation. Patients who underwent lung transplantation from January 2012 to December 2021 were retrospectively analyzed and stratified into three groups: no-AKI, early recovery AKI (within 7 days), and non-early recovery AKI group. AKI occurred in 86 (35%) of patients, of which 40 (16%) achieved early recovery, and the remaining 46 (19%) did not. The median DAOH-90 was 21 days shorter in the AKI than in the no-AKI (P = 0.002), and 29 days shorter in the non-early recovery AKI group than in the no-AKI group (P < 0.001). Non-early recovery AKI and preoperative tracheostomy status were independently associated with shorter DAOH-90. The prevalence of CKD (76%), and 1-year mortality (48%) were highest in the non-early recovery AKI group. Postoperative AKI was associated with an adverse patient-centered quality measure for perioperative care, and shorter DAOH-90. The non-early recovery AKI group exhibited the worst prognosis in terms of DAOH-90, CKD progression, and 1-year mortality, highlighting the important role of AKI and early-recovery AKI on both the quality of life and clinical outcomes after lung transplantation., (© 2024. The Author(s).)

Purpose: Mechanical cardiac constraint during off-pump coronary artery bypass surgery (OPCAB) causes right ventricle (RV) compression and increased pulmonary artery pressure (PAP), which may further compromise RV dysfunction. We aimed to assess the effect of inhaled iloprost, a potent selective pulmonary vasodilator, on the cardiac index (CI) during mechanical constraint. The secondary aim was to determine the resultant changes in the hemodynamic and respiratory parameters., Methods: A total of 100 adult patients with three-vessel coronary artery disease who had known risk factors for hemodynamic instability (congestive heart failure, mean PAP ≥ 25 mm Hg, RV systolic pressure ≥ 50 mm Hg on preoperative echocardiography, left ventricular ejection fraction < 50%, myocardial infarction within one month of surgery, redo surgery, and left main disease) were enrolled in a randomized controlled trial. The patients were randomly allocated to the control or iloprost groups at a 1:1 ratio, in which saline and iloprost (20 μg) were inhaled for 15 min after internal mammary artery harvesting, respectively. Cardiac index was measured by pulmonary artery catheterization., Results: There were no significant intergroup differences in CI during grafting (P = 0.36). The mean PAP had a significant group-time interaction (P = 0.04) and was significantly lower in the iloprost group at circumflex grafting (mean [standard deviation], 26 [3] mm Hg vs 24 [3] mm Hg; P = 0.01). The remaining hemodynamic parameters were similar between the groups., Conclusion: Inhaled iloprost showed a neutral effect on hemodynamic parameters, including the CI and pulmonary vascular resistance index, during OPCAB., Trial Registration: ClinicalTrials.gov (NCT04598191); first submitted 12 October 2020., (© 2023. Canadian Anesthesiologists' Society.)

Acute kidney injury frequently occurs after cardiac surgery, and is primarily attributed to renal ischemia-reperfusion (I/R) injury and inflammation from surgery and cardiopulmonary bypass. Vitamin C, an antioxidant that is often depleted in critically ill patients, could potentially mitigate I/R-induced oxidative stress at high doses. We investigated the effectiveness of high-dose vitamin C in preventing I/R-induced renal injury. The ideal time and optimal dosage for administration were determined in a two-phase experiment on Sprague-Dawley rats. The rats were assigned to four groups: sham, IRC (I/R + saline), and pre- and post-vitC (vitamin C before and after I/R, respectively), with vitamin C administered at 200 mg/kg. Additional groups were examined for dose modification based on the optimal timing determined: V100, V200, and V300 (100, 200, and 300 mg/kg, respectively). Renal I/R was achieved through 45 min of ischemia followed by 24 h of reperfusion. Vitamin C administration during reperfusion significantly reduced renal dysfunction and tubular damage, more than pre-ischemic administration. Doses of 100 and 200 mg/kg during reperfusion reduced oxidative stress markers, including myeloperoxidase and inflammatory responses by decreasing high mobility group box 1 release and nucleotide-binding and oligomerization domain-like receptor 3 inflammasome. Overall beneficial effect was most prominent with 200 mg/kg. The 300 mg/kg dose, however, showed no additional benefits over the IRC group regarding serum blood urea nitrogen and creatinine levels and histological evaluation. During reperfusion, high-dose vitamin C administration (200 mg/kg) significantly decreased renal I/R injury by effectively attenuating the major triggers of oxidative stress and inflammation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Objectives: To investigate the effect of retrograde autologous priming (RAP) on coagulation function using rotation thromboelastometry (ROTEM) in patients undergoing valvular cardiac surgery., Design: A prospective, randomized, patient- and outcome assessor-blinded study., Setting: At a single-center university hospital., Participants: Patients aged 20 years or older undergoing valvular cardiac surgery., Interventions: A total of 104 patients were allocated to the RAP or control group (1:1 ratio). In the RAP group, the prime was displaced into the collection bag before bypass initiation. ROTEM was performed at the induction of anesthesia, at the beginning of rewarming, and after the reversal of heparinization. Allogeneic plasma products and platelet concentrates were transfused according to ROTEM-based algorithms., Measurements and Main Results: An average volume of 635 ± 114 mL was removed using RAP (from the 1,600 mL initial prime volume). The hematocrit 10 minutes after cardiopulmonary bypass (CPB) was 24.7 ± 3.5% in the control group, and 26.1 ± 4.1% in the RAP group (p = 0.330). ROTEM, including EXTEM, INTEM, and FIBTEM, showed prolonged clotting time and decreased maximal clot firmness after CPB in both groups without intergroup differences. The number of patients who received intraoperative erythrocytes (27% v 25%, control versus RAP, p = 0.823), fresh frozen plasma (14% v 8%, control versus RAP, p = 0.339), cryoprecipitate (21% v 12%, control versus RAP, p = 0.185), or platelet concentrate transfusion (19% v 12%, control versus RAP, p = 0.277) did not differ between the groups., Conclusions: Cardiopulmonary bypass induced impaired coagulation function on ROTEM. However, RAP did not improve coagulation function when compared with conventional priming in patients undergoing valvular cardiac surgery., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: The integrity of the endothelial glycocalyx (EG), a critical player in vascular homeostasis, reportedly influences the outcomes of critically ill patients. We investigated the effect of 5% albumin, which preserved EG integrity in preclinical studies, vs balanced crystalloid solution on EG degradation in patients undergoing off-pump coronary surgery., Methods: Patients were randomized to receive either 5% albumin (N = 51) or balanced crystalloid solution (Plasma-Lyte [Baxter Incorporated, Seoul, Republic of Korea]; N = 53) for intravenous volume replacement during surgery (double-blinded). The primary outcome was plasma syndecan-1 concentration, a marker of EG degradation, measured after anesthetic induction (baseline), completion of grafting, and sternal closure. Secondary outcomes were atrial natriuretic peptide (ANP), tumour necrosis factor (TNF)-α, soluble thrombomodulin, and perioperative fluid balance., Results: The mean (standard deviation) fluid requirements were 833 (270) mL and 1,323 (492) mL in the albumin and Plasma-Lyte group, respectively (mean difference, -489 mL; 95% confidence interval [CI], -643 to -335; P < 0.001). Plasma syndecan-1 concentration increased after completion of grafting (median difference, 116 ng·mL -1 ; 95% CI, 67 to 184; P < 0.001) and sternal closure (median difference, 57 ng·mL -1 ; 95% CI, 36 to 80; P < 0.001) compared with those at baseline, without any intergroup differences. Atrial natriuretic peptide, TNF-α, and soluble thrombomodulin concentrations were similar between the two groups. The amount of chest tube drainage was greater in the albumin group than that in the Plasma-Lyte group (median difference, 190 mL; 95% CI, 18 to 276; P = 0.03)., Conclusion: Off-pump coronary surgery was associated with significant EG degradation. Yet, intraoperative fluid therapy with 5% albumin could not ameliorate EG degradation when compared with balanced crystalloid solution., Trial Registration: ClinicalTrials.gov (NCT03699462); first posted 9 October 2018., (© 2023. Canadian Anesthesiologists' Society.)

Introduction: Existing risk-scoring systems for cardiac surgery include only standard preoperative factors without considering nutritional and inflammatory status or intraoperative factors. The objective of this study was to develop a comprehensive prediction model for mortality incorporating nutritional, inflammatory, and perioperative factors in patients undergoing valvular heart surgery., Materials and Methods: In this retrospective review of 2046 patients who underwent valvular heart surgery, Cox and LASSO regression analyses were performed to identify independent prognostic factors for 1-year postoperative mortality among various perioperative factors known to affect prognosis, including objective nutritional and inflammatory indices. A novel nomogram model incorporating selected prognostic factors was developed, and its discrimination ability was evaluated using the C-index. The model was validated in internal and external cohorts., Results: The 1-year mortality rate after valvular heart surgery was 5.1% (105 of 2046 patients) and was significantly associated with several preoperative objective inflammatory and nutritional indices. Cox and LASSO analyses identified the following five independent prognostic factors for mortality: monocyte-to-lymphocyte ratio (an objective inflammatory index), EuroSCORE II, Controlling Nutritional Status score, cardiopulmonary bypass time, and number of erythrocyte units transfused intraoperatively. The nomogram model incorporating these five factors had a C-index of 0.834 (95% CI: 0.791-0.877), which was higher than that of EuroSCORE II alone (0.744, 95% CI: 0.697-0.791) ( P <0.001). The nomogram achieved good discrimination ability, with C-indices of 0.836 (95% CI: 0.790-0.878) and 0.727 (95% CI: 0.651-0.803) in the internal and external validation cohorts, respectively, and showed well-fitted calibration curves., Conclusions: A nomogram model incorporating five inflammatory, nutritional, and perioperative factors, as well as EuroSCORE II, was a better predictor of 1-year mortality after valvular heart surgery than EuroSCORE II alone, with good discrimination and calibration power for predicting mortality in both internal and external validation cohorts., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

The perioperative milieu following curative lung cancer surgery is accompanied by a stress response. Inflammasomes mediate inflammation resulting in the unfavorable immunomodulation of natural killer (NK) cell activity, thus promoting cancer progression. This study aimed to investigate the effects of dexmedetomidine (DEX) on the innate immune system, chronic inflammation, and lung cancer progression in a clinically relevant human-to-mouse xenograft model. The human lung cancer cell line A549-luc was subcutaneously injected into BALB/c nude mice. Saline or dexmedetomidine was administered for 2 weeks via an implanted osmotic minipump. After 4 weeks, the tumor size and weight were measured. NK cell activity, serum interferon-γ, interleukin (IL)-1β and tumor necrosis factor (TNF)-α levels were also measured. IL-10, IL-18, and inflammasome expression levels were assessed in the tumor tissues. DEX caused a decrease in tumor size, tumor weight, and IL-1β and TNF-α levels and an increase in NK cell activity and IFN-γ level. IL-10 and IL-18 expression was significantly decreased in the DEX-treated group. NLRP3, CTP1A, TXNIP, ASC, IL-1β, and caspase-1 protein levels were decreased in the DEX-treated group. In conclusion, the use of DEX for 2 weeks inhibited lung cancer progression by suppressing inflammasome- and IL-1β signaling-induced inflammation and enhancing NK cell activity., (© 2023. The Author(s).)

Off-pump coronary surgery requires mechanical cardiac displacement, which results in bi-ventricular systolic and diastolic dysfunction. Although transient, subsequent hemodynamic deterioration can be associated with poor prognosis and, in extreme cases, emergency conversion to on-pump surgery, which is associated with high morbidity and mortality. Thus, appropriate decision-making regarding whether the surgery can be proceeded based on objective hemodynamic targets is essential before coronary arteriotomy. For adequate hemodynamic management, avoiding myocardial oxygen supply-demand imbalance, which includes maintaining mean arterial pressure above 70 mmHg and preventing an increase in oxygen demand beyond the patient's coronary reserve, must be prioritized. Maintaining mixed venous oxygen saturation above 60%, which reflects the lower limit of adequate global oxygen supply-demand balance, is also essential. Above all, severe mechanical cardiac displacement incurring compressive syndromes, which cannot be overcome by adjusting major determinants of cardiac output, should be avoided. An uncompromising form of cardiac constraint can be ruled out as long as the central venous pressure is not equal to or greater than the pulmonary artery diastolic (or occlusion) pressure, as this would reflect tamponade physiology. In addition, transesophageal echocardiography should be conducted to rule out mechanical cardiac displacement-induced ventricular interdependence, dyskinesia, severe mitral regurgitation, and left ventricular outflow tract obstruction with or without systolic motion of the anterior leaflet of the mitral valve, which cannot be tolerated during grafting. Finally, the ascending aorta should be carefully inspected for gas bubbles to prevent hemodynamic collapse caused by a massive gas embolism obstructing the right coronary ostium.

Background: To maintain adequate oxygenation is of utmost importance in intraoperative care. However, clinical evidence supporting specific oxygen levels in distinct surgical settings is lacking. This study aimed to compare the effects of 30% and 80% oxygen in off-pump coronary artery bypass grafting (OPCAB)., Methods: This multicenter trial was conducted in three tertiary hospitals from August 2019 to August 2021. Patients undergoing OPCAB were cluster-randomized to receive either 30% or 80% oxygen intraoperatively, based on the month when the surgery was performed. The primary endpoint was the length of hospital stay. Intraoperative hemodynamic data were also compared., Results: A total of 414 patients were cluster-randomized. Length of hospital stay was not different in the 30% oxygen group compared to the 80% oxygen group (median, 7.0 days vs 7.0 days; the sub-distribution hazard ratio, 0.98; 95% confidence interval [CI] 0.83-1.16; P = 0.808). The incidence of postoperative acute kidney injury was significantly higher in the 30% oxygen group than in the 80% oxygen group (30.7% vs 19.4%; odds ratio, 1.94; 95% CI 1.18-3.17; P = 0.036). Intraoperative time-weighted average mixed venous oxygen saturation was significantly higher in the 80% oxygen group (74% vs 64%; P < 0.001). The 80% oxygen group also had a significantly greater intraoperative time-weighted average cerebral regional oxygen saturation than the 30% oxygen group (56% vs 52%; P = 0.002)., Conclusions: In patients undergoing OPCAB, intraoperative administration of 80% oxygen did not decrease the length of hospital stay, compared to 30% oxygen, but may reduce postoperative acute kidney injury. Moreover, compared to 30% oxygen, intraoperative use of 80% oxygen improved oxygen delivery in patients undergoing OPCAB. Trial registration ClinicalTrials.gov (NCT03945565; April 8, 2019)., (© 2023. The Author(s).)

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.

Purpose: The estimated glomerular filtration rate (eGFR) at 6 months after donation (eGFR 6m ) is strongly associated with the risk of end-stage renal disease in living kidney donors. This study aimed to investigate the incidence of eGFR 6m <60 mL/min/1.73 m² (eGFR 6m <60) and identify the risk factors that can predict the occurrence of eGFR 6m <60 in living kidney donors., Materials and Methods: Living kidney donors who underwent nephrectomy at Severance Hospital between January 2009 and December 2019 were identified. We excluded 94 of 1233 donors whose creatinine values at 6 months after donation were missing. The risk factors for eGFR 6m <60 were assessed using multivariate regression analysis. The optimal cutoff points for candidate risk factors for predicting eGFR 6m <60 occurrence were determined using the Youden index., Results: The eGFR 6m <60 occurred in 17.3% of the participants. Older age (≥44 years), history of hypertension, lower preoperative eGFR (<101 mL/min/1.73 m²), and degree of increase in creatinine levels on postoperative day 2 compared to those before surgery (ΔCr2&#95;pre) (≥0.39 mg/dL) increased the risk of eGFR 6m <60. The addition of ΔCr2&#95;pre to preoperative eGFR yielded a higher predictive accuracy for predicting eGFR 6m <60 than that with preoperative eGFR alone {area under the receiver operating characteristic curve=0.886 [95% confidence interval (CI), 0.863-0.908] vs. 0.862 (95% CI, 0.838-0.887), p <0.001}., Conclusion: The incidence of eGFR 6m <60 was 17.3%. Older age, lower preoperative eGFR, history of hypertension, and greater ΔCr2&#95;pre were associated with the occurrence of eGFR 6m <60 after living donor nephrectomy. The combination of preoperative eGFR and ΔCr2&#95;pre showed the highest predictive power for eGFR 6m <60., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2023.)

By monitoring the brain as the index organ of global oxygen supply-demand balance including major organs, regional cerebral oxygen saturation (rScO 2 ) may indicate adequacy of renal perfusion. The aim of this study was to investigate the relationship between perioperative rScO 2 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 rScO 2 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% (AUT 50 ) and of 80% of baseline (AUT 80%base ). Among 580 patients, AKI developed in 143 (24.7%) patients. Patients with AKI had lower baseline, mean, and lowest rScO 2 and higher AUT 50 and AUT 80%base than those without AKI despite routine efforts to restore the rScO 2 values within 20% of the baseline. Among the rScO 2 variables, the area under the receiver operating characteristic curve of mean rScO 2 was the highest (0.636), which was used for the multivariable logistic regression. Multivariable logistic regression revealed mean rScO 2 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 rScO 2 was independently associated with AKI after OPCAB, which may serve as an early marker of renal injury.

Aims: 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., Main Methods: 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., Key Findings: 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., Significance: 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., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: 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., Methods: 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., Results: 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., Conclusions: 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., (Copyright © 2021 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

We retrospectively evaluated the association between preoperative mild thyroid dysfunction (subclinical hypothyroidism [SCH] or low triiodothyronine [T3] syndrome) and outcomes in patients who underwent off-pump coronary surgery (OPCAB). Further, 800 patients (2015−2020) were divided into euthyroid, low T3, and SCH groups. The primary outcome assessed the association with composite endpoints (myocardial infarction, prolonged mechanical ventilation [>24 h], acute kidney injury, and 30-day/in-hospital mortality). The secondary outcome assessed the association with long-term mortality and 10% and 8% of the patients exhibited low T3 and SCH, respectively. Incidences of composite endpoints were significantly higher in the low T3 and SCH groups versus the euthyroid group (50.6%, 45.2%, 17.4%, respectively, p < 0.001). Multivariable regression analysis revealed chronic kidney disease, anemia, EuroSCORE, low T3, and SCH as independent risk factors of composite endpoints. The long-term mortality rate (median follow-up, 30 months) was higher in the low T3 and SCH groups than in the euthyroid group (9.6%, 11.3%, 2.4%, respectively, p < 0.001). In the absence of overt thyroid dysfunction, low T3 and SCH were associated with increased risk of adverse outcomes after OPCAB. Moreover, the adverse influences of low T3 and SCH seem to extend to long-term mortality, implying that routine thyroid function tests may enhance accurate risk stratification.

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 P2Y 12 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 P2Y 12 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 P2Y 12 antagonists. The % inhibitory responses to P2Y 12 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 P2Y 12 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.

Comprehensive evidence regarding the treatment of non-anaemic iron deficiency in patients undergoing valvular heart surgery is lacking. This study aimed to investigate the association between non-anaemic iron deficiency and postoperative outcomes in these patients. We retrospectively analysed 321 patients of which 180 (56%) had iron deficiency (defined as serum ferritin < 100 ng.ml -1 or < 300 ng.ml -1 with transferrin saturation < 20%). While the iron-deficient group had lower pre-operative haemoglobin levels than the non-iron deficient group (median (IQR [range]) 134 (127-141 [120-172]) g.l -1 , 143 (133-150 [120-179]) g.l -1 , p = 0.001), there was no between-group difference in allogeneic red blood cell transfusion. Median (IQR [range]) days alive and out of hospital at postoperative day 90 was 1 day shorter in the iron-deficient group (80 (77-82 [9-85]) days vs. 81 (79-83 [0-85]) days, p = 0.026). In multivariable analysis, only cardiopulmonary bypass duration (p = 0.032) and intra-operative allogeneic red blood cell transfusion (p = 0.011) were significantly associated with reduced days alive and out of hospital at postoperative day 90. Iron deficiency did not exert any adverse influence on secondary outcomes except length of hospital stay. Our findings indicate that non-anaemic iron deficiency alone is not associated with adverse effects in patients undergoing valvular heart surgery when it does not translate into an increased risk of allogeneic transfusion., (© 2022 Association of Anaesthetists.)

Purpose: 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., Methods: A total of 104 patients were randomly assigned to receive either an intraoperative infusion of dexmedetomidine 0.4 μg·kg -1 ·hr -1 or 0.9% saline. The primary outcome was the serum creatinine level on postoperative day (POD) 7. Secondary outcomes were renal function and the degree of inflammation and included the following variables: serum creatinine level and estimated glomerular filtration rate up to six months; incidence of delayed graft function; and levels of serum cystatin C, plasma interleukin (IL)-1β, and IL-18 during the perioperative period., Results: The mean (standard deviation) serum creatinine level on POD 7 was comparable between the groups (dexmedetomidine vs control: 1.11 [0.87] mg·dL -1 vs 1.06 [0.73] mg·dL -1 ; mean difference, 0.05; 95% confidence interval, -0.27 to 0.36; P = 0.77). Delayed graft function occurred in one patient in each group (odds ratio, 1.020; P > 0.99). There were no significant differences in the secondary outcomes between the groups (all P > 0.05)., Conclusions: Intraoperative dexmedetomidine infusion did not produce any beneficial effects on renal function or delayed graft function in patients undergoing elective living donor kidney transplantation., Study Registration: www., Clinicaltrials: gov (NCT03327389); registered 31 October 2017., (© 2021. Canadian Anesthesiologists' Society.)

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., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: We investigated whether routine perioperative intravenous iron replenishment reduces the requirement for packed erythrocytes (pRBC) transfusion., Summary of 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., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

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., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

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 siRNA s 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., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2021 Hye-Bin Kim et al.)

Purpose: This study sought to compare clinical outcomes between transcatheter aortic valve replacement (TAVR) and sutureless aortic valve replacement (SU-AVR)., Materials and Methods: In total, 320 patients with symptomatic severe aortic stenosis who underwent TAVR (n=254) or SU-AVR (n=66) at Severance Cardiovascular Hospital between July 2011 and September 2019 were included for analysis. Propensity score matching and inverse probability weighted adjustment were performed to adjust for confounding baseline characteristics. Outcomes defined by the Valve Academic Research Consortium-2 in 62 patients pairs were compared., Results: Device success (79.0% vs. 79.0%, p >0.999) and 30-day mortality (4.8% vs. 0.0%, p =0.244) did not differ between the TAVR and SU-AVR groups. The TAVR group developed more frequent mild or moderate paravalvular leakage (59.7% vs. 8.1%, p <0.001), whereas SU-AVR was associated with higher rates of major or life-threatening bleeding (9.7% vs. 22.6%, p =0.040), acute kidney injury (8.1% vs. 21.0%, p =0.041), and new-onset atrial fibrillation (4.8% vs. 32.3%. p <0.001) at 30 days, along with longer stays in the intensive care unit (ICU) (1.9±1.6 days vs. 5.9±9.2 days, p =0.009) and hospital (7.1±7.9 days vs. 13.1±8.8 days, p <0.001). The TAVR group showed a trend towards a higher 1-year all-cause mortality, compared with the SU-AVR group (7.0% vs 1.7%, p =0.149). Cardiovascular mortality, however, did not differ significantly (1.6% vs 1.7%, p =0.960)., Conclusion: TAVR achieved a similar 1-year survival rate free from cardiovascular mortality as SU-AVR and was associated with a lower incidence of complications, except for paravalvular leakage, and shorter stays in the ICU and hospital., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2021.)

When hemoglobin (Hb) is fully saturated with oxygen, the additional gain in oxygen delivery (DO 2 ) achieved by increasing the fraction of inspired oxygen (FiO 2 ) is often considered clinically insignificant. In this study, we evaluated the change in DO 2 , interrogated by mixed venous oxygen saturation (SvO 2 ), in response to a change in FiO 2 of 0.5 during cardiac surgery. When patients were hemodynamically stable, FiO 2 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 SvO 2 . The observed change in SvO 2 (ΔSvO 2 ) was compared to the expected ΔSvO 2 calculated using Fick's equation. A total 106 changes in FiO 2 (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 FiO 2 was 0.3 and 99.9% [0.2] when FiO 2 was 0.8), SvO 2 changed significantly as FiO 2 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 < 0.001). As a total, regardless of the surgery type, the observed ΔSvO 2 after the FiO 2 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 ΔSvO 2 (the first changes, r =  - 0.06, P = 0.677; the second changes, r =  - 0.21, P = 0.138). The mean (SD) residual ΔSvO 2 (observed - expected ΔSvO 2 ) was 0%p (4). Residual ΔSvO 2 was more than 5%p in 14 (13.2%) changes and exceeded 10%p in 2 (1.9%) changes. Residual ΔSvO 2 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). DO 2 , interrogated by SvO 2 , may increase to a clinically significant degree as FiO 2 is increased during cardiac surgery, and the increase of SvO 2 is not related to Hb concentration. SvO 2 increases more than expected in patients with chronic kidney disease. Increasing FiO 2 can be used to increase DO 2 during cardiac surgery., (© 2021. The Author(s).)

Sarcopenia along with nutritional status are associated with postoperative pulmonary complications in various surgical fields. Recently, the creatinine/cystatin C ratio and CONtrolling NUTritional status score were introduced as biochemical indicators for sarcopenia and malnutrition, respectively. We aimed to investigate the associations among these indicators and postoperative pulmonary complications in elderly patients undergoing off-pump coronary artery bypass surgery. We reviewed the medical records of 605 elderly patients (aged ≥ 65 years) who underwent off-pump coronary artery bypass surgery from January 2010 to December 2019. Postoperative pulmonary complications (pneumonia, prolonged ventilation [> 24 h], and reintubation during post-surgical hospitalisation) occurred in 80 patients. A 10-unit increase of creatinine/cystatin C ratio was associated with a reduced risk of postoperative pulmonary complications (odds ratio: 0.80, 95% confidence interval: 0.69-0.92, P = 0.001); the optimal cut-off values for predicting postoperative pulmonary complications was 89.5. Multivariable logistic regression analysis revealed that age, congestive heart failure, and creatinine/cystatin C ratio < 89.5 (odds ratio 2.36, 95% confidence interval 1.28-4.37) were independently associated with the occurrence of postoperative pulmonary complications, whereas CONtrolling NUTritional status score was not. A low creatinine/cystatin C ratio was associated with an increased risk of developing postoperative pulmonary complications after off-pump coronary artery bypass surgery., (© 2021. The Author(s).)

Purpose: 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., Methods: 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., Results: 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)., Conclusions: 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., Trial Registration: www.clinicaltrial.gov (NCT03273231); registered 6 September 2017.

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 < 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.

Objective: 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., Methods: 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., Results: 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., Conclusions: 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., (Copyright © 2019 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)