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Hayato Ise,1,2 Ryohei Ushioda,1 Hirotsugu Kanda,3 Fumiaki Kimura,4 Yasuaki Saijo,5 Payam Akhyari,2 Artur Lichtenberg,2 Hiroyuki Kamiya1 1Department of Cardiac Surgery, Asahikawa Medical University, Asahikawa, Japan; 2Department of Cardiovascular Surgery, Heinrich Heine University, Düsseldorf, Germany; 3Department of Anesthesiology and Critical Care Medicine, Asahikawa Medical University, Asahikawa, Japan; 4Department of Cardiovascular Surgery, Kushiro Kojinkai Memorial Hospital, Kushiro, Japan; 5Division of Public Health and Epidemiology, Department of Social Medicine, Asahikawa Medical University, Asahikawa, JapanCorrespondence: Hirotsugu Kanda, Department of Anesthesiology and Critical Care Medicine, Asahikawa Medical University, Midorigaoka-Higashi 2-1-1-1, Asahikawa, 078-8510, Japan, Tel +81-166-68-2583, Fax +81-166-68-2589, Email hirotsugukanda0629@gmail.comPurpose: We aimed to identify the risk factors of critical bleeding and investigate the safety of recombinant activated factor VII (rFVIIa) in aortic surgery under hypothermic circulatory arrest (HCA).Patients and Methods: The present single-center retrospective study compared the baseline characteristics of 144 patients who underwent aortic surgery under HCA at our institute. Among the total cohort of 144 patients, 42 received rFVIIa (rFVIIa group), while the remaining 102 patients did not (non-rFVIIa group). Perioperative bleeding and transfusions, postoperative 30-day mortality, and adverse events (AEs) were analyzed in 29 propensity score-matched pairs.Results: Before surgery, the rFVIIa group demonstrated a greater number of shocks (p=0.019), higher JapanSCORE II mortality rate (p=0.033), low platelet count (p=0.015) and fibrinogen (p< 0.001) level, prolonged activated partial thromboplastin time (aPTT) (p=0.005) and prothrombin time international normalized ratio (PT-INR) (p=0.006), and longer aortic cross clamp time (p=0.049). Postoperative bleeding, transfusion, 30-day mortality, and AEs were comparable between the groups both in the entire-unmatched cohort and propensity score matching cohort.Conclusion: Preoperative shock, higher JapanSCORE II mortality rates, low platelet and fibrinogen levels, prolonged aPTT and PT-INR, and longer aortic clamping time might be risk factors for excessive bleeding and indicate the need for rFVIIa treatment. The present study suggests that rFVIIa can be safely used to address critical and continuous bleeding in spite of adequate transfusion and supplementation of other coagulation factors in aortic surgery under HCA, without an increase in 30-day mortality and AEs.Keywords: aortic surgery under hypothermic circulatory arrest, cardiac surgery, recombinant activated factor VII, retrospective study, uncontrollable bleeding

Background IL-13 induces goblet cell hyperplasia and mucus overproduction in airway epithelial cells. IL-13 receptor α2 (IL-13Rα2) has been suggested to act as a ‘decoy receptor’ in the airway epithelium by inhibiting the IL-13 signal. However, the regulatory mechanisms for mucus production by IL-13Rα2 remain unclear. Objective The aim of this study was to examine the role of IL-13Rα2 in goblet cell hyperplasia and mucus overproduction by IL-13. Methods Bronchi were obtained from patients who underwent a lung resection due to lung cancer or benign lung tumours. Normal human bronchial epithelial cells (NHBECs) were isolated and cultured using an air–liquid interface (ALI) method. Results The number of periodic acid-Schiff's (PAS)-positive cells, goblet cells and MUC5AC-positive cells increased after adding IL-13 into NHBECs. The concentrations of MUC5AC protein in the supernatant and the mRNA expression of MUC5AC significantly increased after adding IL-13, and returned to control levels at 21 days. The mRNA expression of IL-13Rα2 significantly increased at 7 days and then continuously increased up to 21 days. The protein of a soluble form of IL-13Rα2 in the supernatants significantly increased at 14 and 21 days. Anti-IL-13Rα1 antibody and recombinant IL-13Rα2 reduced the number of PAS-positive cells, goblet cells and MUC5AC-positive cells, and MUC5AC mRNA, while the anti-IL-13Rα2 antibody increased the number of these cells and MUC5AC mRNA. The concentration of MUC5AC protein in the supernatant induced by IL-13 was reduced by anti- IL-13Rα1 antibody and recombinant IL-13Rα2. IL-13-induced signal transducer and activator of transcription (STAT) activation was inhibited by anti-IL-13Rα1 antibody and recombinant IL-13Rα2. In contrast, the IL-4-induced mucus production, mucus secretion and STAT activation were not inhibited by recombinant IL-13Rα2. Conclusion The soluble form of IL-13Rα2 may therefore modulate mucus overproduction by IL-13 through the pathway including IL-13Rα1 in NHBECs. [ABSTRACT FROM AUTHOR]

It is believed that a lower temperature setting of hypothermic circulatory arrest (HCA) in thoracic aortic surgery causes coagulopathy, resulting in excessive bleeding. However, experimental studies that eliminate clinical factors are lacking. The objective of this study is to investigate the influence of the temperature setting of HCA on coagulation in a pig model. Ten pigs were divided into the following two groups: moderate temperature at 28 °C (group M, n = 5) or lower temperature at 20 °C (group L, n = 5). Two hours of HCA during a total of 4 h of cardiopulmonary bypass (CPB) were performed. Blood samples were obtained at the beginning (T1) and the end (T2) of the surgery, and coagulation capability was analyzed through standard laboratory tests (SLTs) and rotational thromboelastometry (ROTEM). In SLTs, hemoglobin, fibrinogen, platelet count, prothrombin time, and activated partial thromboplastin time were analyzed. In ROTEM analyses, clotting time and clot formation time of EXTEM, maximum clot firmness (MCF), and maximum clot elasticity (MCE) of EXTEM and FIBTEM were analyzed. Fibrinogen decreased significantly in both groups (group M, p = 0.008; group L, p = 0.0175) at T2, and FIBTEM MCF and MCE also decreased at T2. There were no differences regarding changes in parameters of SLTs and ROTEM between groups. CPB decreases coagulation capacity, contributed by fibrinogen. However, a lower temperature setting of HCA at 20 °C for 2 h did not significantly affect coagulopathy compared to that of HCA at 28 °C after re-warming to 37 °C., (© 2024. The Author(s).)

Background: Acute aortic dissection type A (AADA) is associated with high perioperative morbidity and mortality. A novel non-covered hybrid prosthesis (AMDS, CryoLife, Kennesaw, USA) can be easily implanted to stabilize the true lumen. However, the role of AMDS for patients requiring additional aortic root surgery has not been described., Methods: Between 2010 and 2020 a total of n = 370 patients underwent surgery for AADA in our department. Of those, n = 120 underwent treatment for aortic root in addition to proximal arch replacement without resection of the aorta beyond the innominate artery (Control, n = 111) and were compared to patients who received additional AMDS implantation (AMDS, n = 9)., Results: Aortic valve repair was performed in 48.6% (Control) and in 55.6% of AMDS patients. Cardiopulmonary bypass (Control: 248 ± 76 min, AMDS: 313 ± 53 min, P < 0.01) time as well as circulatory arrest time of the lower body (Control: 30 ± 15 min, AMDS: 52 ± 12 min, P < 0.01) was prolonged in the AMDS group. Nevertheless, postoperative in-hospital morbidity such as dialysis (Control: 22.4%, AMDS: 11.1%, P = 0.68) and stroke (Control: 17.0%, AMDS: 22.2%, P = 0.65) were comparable. In-hospital death (Control: 21.8%, AMDS: 11.1%, P = 0.68) and the compound end-point MACCE (Control: 38.7%, AMDS: 44.4%, P = 0.74) did also not differ., Conclusions: Addressing the arch by implantation of AMDS prolongs cardiopulmonary bypass and circulatory arrest time, however without relevant impairments of short-term outcome. Combining root surgery with replacement of the proximal aortic arch and AMDS implantation seems feasible and safe as it did not impair the early postoperative outcome., (© 2023. The Author(s).)

O-linked β-N-acetylglucosamine (O-GlcNAc)-modified proteins are post-translationally modified with GlcNAc conjugated to serine and threonine residues. This modification is associated with various physiological functions such as serine and threonine phosphorylation and Notch signaling. Here, we demonstrated that O-GlcNAc-modified proteins leaked from dead cells and GlcNAc-bearing polymers mimicking the multivalent GlcNAc moiety of these proteins induced anti-fibrotic activities, such as the suppression of α-smooth muscle actin and collagen and the induction of matrix metalloprotease 1 in myofibroblasts. We have previously reported that O-GlcNAc-modified proteins and GlcNAc-bearing polymers could interact with cell surface vimentin and desmin. In the current study, it was demonstrated that a multivalent GlcNAc moiety structure of these molecules activated PI3K/Akt and p38MAPK pathway and elicited these anti-fibrotic activities in myofibroblasts by interacting with cell surface vimentin. Since the interaction of O-GlcNAc-modified proteins with desmin was observed in the fibrotic liver of carbon tetrachloride-treated mice via an in situ proximity ligation assay, it was assumed that the activated stellate cells could bind to the O-GlcNAc-modified proteins from the damaged hepatocytes. In addition, the administration of anti-O-GlcNAc antibody to inhibit the interaction exacerbated liver fibrosis in the mice. Moreover, administration of the GlcNAc-bearing polymers into carbon tetrachloride-treated mice could ameliorate liver fibrosis. Thus, O-GlcNAc-modified proteins leaked from dead cells can interact with myofibroblasts and activated stellate cells and function as fibrosis suppressors. Moreover, we anticipate that GlcNAc-bearing polymers mimicking O-GlcNAc-modified proteins will be applied as novel therapeutic tools for fibrosis., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Hypothermic circulatory arrest (HCA) is an essential procedure during aortic surgery to protect organs; however, hypothermia is believed to cause coagulopathy, which is a major fatal complication. This study aimed to clarify the impact of hypothermia on coagulation by eliminating clinical biases in vitro. In the hypothermic storage study, blood samples from five healthy volunteers were stored at 37 ℃ (group N) for 3 h or at 20 ℃ for 2 h, followed by 1 h of rewarming at 37 ℃ (group H). Thromboelastography was performed before and after 3 h of storage. In the mock circulation loop (MCL) study, blood samples were placed in the MCL and (a) maintained at 37 ℃ for 4 h (group N, n = 5), or (b) cooled to 20 ℃ to simulate HCA with a 0.1 L/min flow rate for 3 h and then rewarmed to 37 ℃ (group H, n = 5). The total MCL duration was 4 h, and the flow rate was maintained at 1 L/min, except during HCA. Blood samples collected 15 min after the beginning and end of MCL were subjected to standard laboratory tests and rotational thromboelastometry analyses. Hypothermia had no impact on coagulation in both the hypothermic storage and MCL studies. MCL significantly decreased the platelet counts and clot elasticity in the INTEM and EXTEM assays; however, there was no effect on fibrinogen contribution measured by FIBTEM. Hypothermia does not cause irreversible coagulopathy in vitro; however, MCL decreases coagulation due to the deterioration of platelets., (© 2022. The Author(s).)

Purpose: The effect of chronic limb threatening ischemia (CLTI) on advanced cardiac disease, which requires surgical treatment, has rarely been reported. The purpose of this study was to review the outcomes of cardiac surgery in patients with CLTI and determine the risk factors, with a particular focus on the severity of CLTI., Patients: The baseline characteristics and outcomes of 33 patients who were treated for CLTI and underwent cardiac surgery were retrospectively analyzed. The states of CLTI were evaluated based on the Wound, Ischemia, and foot Infection (WIfI) classification system, and 33 patients were divided into the low-WIfI group (stages 1-2, n  = 13) and high-WIfI group (stages 3-4, n  = 20)., Results: The in-hospital mortality rate was 0% in low-WIfI group and 35% in high-WIfI group ( p  = 0.027). Postoperative complications, particularly severe infections, occurred more frequently among high-WIfI group than low-WIfI group (70.0% vs. 23.1%, p  < 0.01). Multivariable analysis identified foot infection grade as a WIfI classification factor and lower albumin levels as factors significantly associated with postoperative complications. The 1-year and 2-year survival rates were 84.6% and 67.7% in low-WIfI group and 45% and 28.1% in high-WIfI group, respectively ( p  = 0.011)., Conclusions: Cardiac surgery in patients with high WIfI stage was an extremely high-risk procedure. In such patients, lowering the WIfI stage by lower extremity revascularization and/or debridement of diseased parts prior to cardiac surgery can be considered., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wakabayashi, Kikuchi, Kuriyama, Kikuchi, Tsutsui, Ise, Yoshida, Uchida, Koya, Shirasaka, Azuma and Kamiya.)

Background: The aim of the present study was to validate safety of total arch replacement (TAR) using a novel frozen elephant trunk device, operated by trainees as surgical education., Methods: Sixty-four patients including 19 patients (29.6%) with acute aortic dissection type A (AADA) underwent TAR in our institute between April 2014 and March 2019 were retrospectively analyzed. Twenty-nine patients were operated by trainees (group T) and 35 patients were operated by attending surgeons (group A)., Results: Patient characteristics did not differ between groups. Operative time (409.4 ± 87.8 vs. 468.6 ± 129.6 minutes, p  = 0.034), cardiopulmonary bypass time (177.7 ± 50.4 vs. 222.9 ± 596.7 minutes, p  = 0.019), and hypothermic circulatory arrest time (39.5 ± 13.4 vs. 54.5 ± 18.5 minutes, p  = 0.001) were significantly shorter in group A than in group T, but aortic clamping time did not differ between groups (115.3 ± 55.7 vs. 114.2 ± 35.0 minutes, p  = 0.924) because the rate of concomitant surgery was higher in group A (37.1 vs. 10.3%, p  = 0.014). Thirty-day mortality was 3.1% in the entire cohort. Although operation time was longer in group T, there were no significant difference in postoperative results between the groups, and the experience levels of the main operator were not independent predictors for in-hospital mortality + major postoperative complications. There was no difference in late death and aortic events between groups., Conclusions: The present study demonstrated that TAR can be safely performed by trainees, and suggests TAR as a possible and safe educational operation., Competing Interests: The authors declare that they have no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

We have reported that cytoskeletal proteins such as desmin and vimentin are expressed on the surface of muscle, mesenchymal and cancer cells, and possess N-acetyl-β-D-glucosamine (β-GlcNAc) residue-binding properties. As cell-recognizable β-GlcNAc residue-bearing biopolymer, we prepared glycoconjugates (SF-GlcNAc) composed of silk fibroin (SF) and monosaccharide N-acetyl-D-glucosamine (GlcNAc) by chemical modification using cyanuric chloride. The covalent immobilization of GlcNAc into SF was assessed by 1 H-NMR measurements. The 1 H-NMR spectrum of SF-GlcNAc conjugates showed new peaks attributed to the methyl protons of the N-acetyl group in GlcNAc, and the integration of these peaks revealed that the GlcNAc content in the conjugates was 9 wt%. The existence of β-GlcNAc residues in SF-GlcNAc was examined by the criteria using lectins such as wheat germ agglutinin (WGA). Addition of WGA to SF-GlcNAc solution caused an increase in the turbidity of the solution due to lectin-mediated aggregation. Solid-phase lectin binding assay based on the biotin-avidin interaction showed that biotinylated succinylated WGA bound more strongly onto SF-GlcNAc conjugate-coated wells compared to SF-coated well. Following the establishment of the existence of β-GlcNAc residues in SF-GlcNAc, the interaction of SF-GlcNAc with desmin was examined by enzyme-linked immunosorbent assay using anti-desmin antibody. The stronger binding of desmin was observed for SF-GlcNAc conjugate-coated wells compared to SF-coated wells. The use of SF-GlcNAc conjugates as a substrate for culturing desmin-expressing human cardiac myocytes demonstrated an increase in the numbers of attached cells and proliferating cells on the conjugate-coated wells compared to SF-coated wells. These results suggest that the immobilization of monosaccharide GlcNAc is a useful method for the versatile functionalization of SF as an application in tissue engineering., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objectives: Hypothermic circulatory arrest (HCA) has been considered to cause coagulopathy during cardiac surgery. However, coagulopathy associated with HCA has not been understood clearly in details. The objective of this study is to analyze the details of coagulopathy related to HCA in cardiac surgery by using rotational thromboelastometry (ROTEM)., Methods: We retrospectively analyzed 38 patients who underwent elective cardiac surgery (HCA group = 12, non-HCA group = 26) in our hospital. Blood samples were collected before and after cardiopulmonary bypass (CPB). Standard laboratory tests (SLTs) and ROTEM were performed. We performed four ROTEM assays (EXTEM, INTEM, HEPTEM and FIBTEM) and analyzed the following ROTEM parameters: clotting time (CT), clot formation time (CFT), maximum clot firmness (MCF) and maximum clot elasticity (MCE). The amount of perioperative bleeding, intraoperative transfusion and perioperative data were compared between the HCA and non-HCA group., Results: Operation time and hemostatic time were significantly longer in the HCA group, whereas CPB time had no difference between the groups. The amount of perioperative bleeding and intraoperative transfusion were much higher in the HCA group. SLTs showed no difference between the groups both after anesthesia induction and after protamine reversal. In ROTEM analysis, MCE contributed by platelet was reduced in the HCA group, whereas MCE contributed by fibrinogen had no difference., Conclusion: Our study confirmed that the amount of perioperative bleeding and intraoperative transfusion were significantly higher in the HCA group. ROTEM analysis would indicate that clot firmness contributed by platelet component is reduced by HCA in cardiac surgery.