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This article discusses the use of phage therapy as an alternative or adjunct to antibiotics in the treatment of bacterial infections in heart and lung transplant patients. The authors describe five cases in which phage therapy was successfully used to treat multidrug-resistant infections in transplant patients. The therapy was personalized based on the specific bacteria involved, and in all cases, the pathogen was completely eradicated after phage therapy. The authors conclude that personalized phage therapy can be recommended for critical conditions in transplantation medicine when conventional antibacterial therapy is inadequate. [Extracted from the article]

This article discusses the development of methods to predict the effectiveness of bacteriophage therapy for surgical site infections after cardiovascular surgery. Surgical site infections are a concern, especially when they involve multidrug-resistant pathogens. Phages, which are viruses that can target and kill bacteria, are being explored as an alternative or supplement to antibiotics. The study describes the development of gelatin-based scaffolds to simulate the conditions in treated tissues and evaluate the protective effect and adhesion rate of bacteriophages. These methods can help optimize phage therapy regimens and establish evidence-based guidelines for their use in cardiovascular surgery. [Extracted from the article]

Objective: The frozen elephant trunk is a standard treatment method for aortic arch pathologies extending into the descending aorta. We previously described the phenomenon of early postoperative intraluminal thrombosis within the frozen elephant trunk. We investigated the features and predictors of intraluminal thrombosis., Methods: A total of 281 patients (66% male, mean age 60 ± 12 years) underwent frozen elephant trunk implantation between May 2010 and November 2019. In 268 patients (95%), early postoperative computed tomography angiography was available to assess intraluminal thrombosis., Results: The incidence of intraluminal thrombosis after frozen elephant trunk implantation was 8.2%. Intraluminal thrombosis was diagnosed early after the procedure (4.6 ± 2.9 days) and could be successfully treated with anticoagulation in 55% of patients. A total of 27% developed embolic complications. Mortality (27% vs 11%, P = .044) and morbidity were significantly higher in patients with intraluminal thrombosis. Our data showed a significant association of intraluminal thrombosis with prothrombotic medical conditions and anatomic slow flow features. The incidence of heparin-induced thrombopenia was higher in patients with intraluminal thrombosis (18% vs 3.3%, P = .011). Stent-graft diameter index, anticipated endoleak Ib, and degenerative aneurysm were significant independent predictors of intraluminal thrombosis. Therapeutic anticoagulation was a protective factor. Glomerular filtration rate, extracorporeal circulation time, postoperative rethoracotomy, and intraluminal thrombosis (odds ratio, 3.19, P = .047) were independent predictors of perioperative mortality., Conclusions: Intraluminal thrombosis is an underrecognized complication after frozen elephant trunk implantation. In patients with risk factors of intraluminal thrombosis indication for frozen elephant trunk should be carefully evaluated and postoperative anticoagulation considered. Early thoracic endovascular aortic repair extension should be considered in patients with intraluminal thrombosis to prevent embolic complications. Stent-graft designs should be improved to prevent intraluminal thrombosis after frozen elephant trunk implantation., (Copyright © 2023 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Introduction: Acute type A aortic dissection (ATAAD) is one of the most critical emergencies in cardiovascular surgery. Additional complications such as organ malperfusion can significantly decrease the chances of survival. Despite promptly performed surgical treatment, impaired organ perfusion may persist, thus close postoperative monitoring is recommended. But, is there a surgical consequence due to the existence of a preoperatively known malperfusion and is there a correlation between pre-, peri- and postoperative levels of serum lactate and proven malperfusion?, Methods: Between 2011 and 2018, 200 patients (66% male; median age: 62.5 years; interquartile range: +/-12.4 years) that received surgical treatment at our institution for an acute dissection DeBakey type I were enrolled in this study. The cohort was divided into two groups according to the preoperative existence of malperfusion and non-malperfusion. At least one kind of malperfusion occurred in 74 patients (Group A: 37%), while 126 patients (Group B: 63%) showed no evidence of malperfusion. Furthermore, lactate levels of both cohorts were differentiated into four periods: preoperative, intraoperative, 24 hours after surgery, and 2-4 days after surgery., Results: The patients' status differed significantly prior to surgery. Group A (malperfusion) showed an elevated requirement for mechanical resuscitation (A: 10.8%; B: 5.6%; p : 0.173), were significantly more often admitted in an intubated state (A: 14.9%; B: 2.4%; p : 0.001) and showed higher incidences of stroke (A: 18.9% ( n = 149); B: 3.2% ( n = 4); p : 0.001). Levels of serum lactate from the preoperative period until days 2-4 were significantly increased in the malperfusion cohort at all times., Conclusions: Preexisting malperfusion due to ATAAD may significantly increase the chance of early mortality in patients with ATAAD. Serum lactate levels were a reliable marker for inadequate perfusion from admission until day 4 after surgery. Despite this, early intervention survival in this cohort remains limited., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Intercostal artery reinsertion (ICAR) during thoracoabdominal aortic replacement remains controversial. While some groups recommend the reinsertion of as many arteries as possible, others consider the sacrifice of multiple intercostals practicable. This study investigates the impact of intercostal artery reinsertion or sacrifice on neurological outcomes and long-term survival after thoracoabdominal aortic repair., Methods: A total of 349 consecutive patients undergoing thoracoabdominal aortic replacement at our institution between 1996 and 2021 were analyzed in a retrospective single-center study. ICAR was performed in 213 patients, while all intercostal arteries were ligated and sacrificed in the remaining cases. The neurological outcome was analyzed regarding temporary and permanent paraplegia or paraparesis., Results: No statistically significant differences were observed between the ICAR and non ICAR groups regarding the cumulative endpoint of transient and permanent spinal cord-related complications (12.2% vs. 11.8%, p = 0.9). Operation, bypass, and cross-clamp times were significantly longer in the ICAR group. Likewise, prolonged mechanical ventilation was more often necessary in the ICAR group (26.4% vs. 16.9%, p = 0.03). Overall long-term survival was similar in both groups in the Kaplan-Meier analysis., Conclusion: Omitting ICAR during thoracoabdominal aortic replacement may reduce operation and cross-clamp times and thus minimize the duration of intraoperative spinal cord hypoperfusion.

Free heme is released from hemoproteins during hemolysis or ischemia reperfusion injury and can be pro-inflammatory. Most studies on nephrotoxicity of hemolysis-derived proteins focus on free hemoglobin (fHb) with heme as a prosthetic group. Measurement of heme in its free, non-protein bound, form is challenging and not commonly used in clinical routine diagnostics. In contrast to fHb, the role of free heme in acute kidney injury (AKI) after cardiopulmonary bypass (CPB) surgery is unknown. Using an apo-horseradish peroxidase-based assay, we identified free heme during CPB surgery as predictor of AKI in patients undergoing cardiac valve replacement (n = 37). Free heme levels during CPB surgery correlated with depletion of hemopexin (Hx), a heme scavenger-protein. In mice, the impact of high levels of circulating free heme on the development of AKI following transient renal ischemia and the therapeutic potential of Hx were investigated. C57BL/6 mice were subjected to bilateral renal ischemia/reperfusion injury for 15 min which did not cause AKI. However, additional administration of free heme in this model promoted overt AKI with reduced renal function, increased renal inflammation, and reduced renal perfusion on functional magnetic resonance imaging. Hx treatment attenuated AKI. Free heme administration to sham operated control mice did not cause AKI. In conclusion, free heme is a predictor of AKI in CPB surgery patients and promotes AKI in transient renal ischemia. Depletion of Hx in CPB surgery patients and attenuation of AKI by Hx in the in vivo model encourage further research on Hx therapy in patients with increased free heme levels during CPB surgery., (© 2023 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Introduction: Acute aortic dissection Stanford type A (AADA) is a surgical emergency associated with high morbidity and mortality. Although surgical management has improved, the optimal therapy is a matter of debate. Different surgical strategies have been proposed for patients under 60 years old. This paper evaluates the postoperative outcome and the need for secondary aortic operation after a limited surgical approach (proximal arch replacement) vs. extended arch repair., Methods: Between January 2000 and January 2018, 530 patients received surgical treatment for AADA at our hospital; 182 were under 60 years old and were enrolled in this study - Group A (n=68), limited arch repair (proximal arch replacement), and group B (n=114), extended arch repair (> proximal arch replacement)., Results: More pericardial tamponade (P=0.005) and preoperative mechanical resuscitation (P=0.014) were seen in Group A. More need for renal replacement therapy (P=0.047) was seen in the full arch group. Mechanical ventilation time (P=0.022) and intensive care unit stay (P<0.001) were shorter in the limited repair group. Thirty-day mortality was comparable (P=0.117). New onset of postoperative stroke was comparable (Group A four patients [5.9%] vs. Group B 15 patients [13.2%]; P=0.120). Long-term follow-up did not differ significantly for secondary aortic surgery., Conclusion: Even though young patients received only limited arch repair, the outcome was comparable. Full-arch replacement was not beneficial in the long-time follow-up. A limited approach is justified in the cohort of young AADA patients. Exemptions, like known Marfan syndrome and the presence of an intimal tear in the arch, should be considered.

Background: Severe acute respiratory distress syndrome (ARDS) due to Coronavirus Disease-19 (COVID-19) is associated with high mortality. Although survival on mechanical circulatory support has improved, determinants for better prognosis are still unclear. Here, we report on the outcome of our patient population with the need for mechanical circulatory support due to severe COVID-19 (sCOVID-19) induced ARDS., Methods: All patients treated with extracorporeal membrane oxygenation (ECMO) for severe ARDS due to sCOVID-19 were analysed. Patients > 18 years of age at the time of initiation of ECMO were included. Pre-existing comorbidities, complications during ECMO implantation, and ECMO runtime were reviewed. The latency to intubation, proning, tracheotomy, and ECMO implantation was analysed. Furthermore, the survival and non-survival population were compared to determine factors in favour of a better outcome., Results: In total, 85 patients were treated with veno-venous membrane oxygenation (vv-ECMO) for severe ARDS in our medical centre. The patient population was predominantly male (83.5%) with a mean patient age of 54.9 years. A history of cardiovascular disease ( p = .01), smoking ( p < .05), need for vasopressor- ( p < .05), and renal replacement therapy ( p < .001) was associated with a worse prognosis. Overall survival was 50%. The survival population was significantly younger ( p = .004), had a significantly higher body weight ( p = .02) and body mass index (BMI) ( p = .01). Furthermore, survival was significantly better when vv-ECMO was initiated within 48 h after admission ( p < .001)., Conclusions: Pre-existing cardiovascular disease, higher age, history of nicotine abuse, and development of renal failure are associated with poor outcome. Early start of vv-ECMO therapy may lead to better survival in sCOVID-19 patients, although complications during ECMO therapy are associated with a worse prognosis., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Minimally invasive techniques have gained immense importance in cardiovascular surgery. While minimal access strategies for coronary and mitral valve surgery are already widely accepted and often used as standard approaches, the application of minimally invasive techniques is currently expanded towards more complex operations of the ascending aorta as well. In this new and developing field, various techniques have been established and reported ranging from upper hemisternotomy approaches, which allow even extensive operations of the ascending aorta to be performed through a minimally invasive access to sternal sparing thoracotomy strategies, which completely avoid sternal trauma during ascending aorta replacements. All of these techniques place high demands on patient selection, preoperative planning, and practical surgical implementation. Application of these strategies is currently limited to high-volume centers and highly experienced surgeons. This narrative review gives an overview of the currently available techniques with a special focus on the practical execution as well as the advantages and disadvantages of the currently available techniques. The first results demonstrate the practicability and safety of minimally invasive techniques for replacement of the ascending aorta in a well-selected patient population. With success and complication rates comparable to classic full sternotomy, the proof of concept for minimally invasive replacement of the ascending aorta is now achieved.

Background: Transplant candidates on the waiting list are increasingly challenged by the lack of organs. Most of the organs can only be kept viable within very limited timeframes (e.g., mere 4-6 h for heart and lungs exposed to refrigeration temperatures ex vivo). Donation after circulatory death (DCD) using extracorporeal membrane oxygenation (ECMO) can significantly enlarge the donor pool, organ yield per donor, and shelf life. Nevertheless, clinical attempts to recover organs for transplantation after uncontrolled DCD are extremely complex and hardly reproducible. Therefore, as a preliminary strategy to fulfill this task, experimental protocols using feasible animal models are highly warranted. The primary aim of the study was to develop a model of ECMO-based cadaver organ recovery in mice. Our model mimics uncontrolled organ donation after an "out-of-hospital" sudden unexpected death with subsequent "in-hospital" cadaver management post-mortem. The secondary aim was to assess blood gas parameters, cardiac activity as well as overall organ state. The study protocol included post-mortem heparin-streptokinase administration 10 min after confirmed death induced by cervical dislocation under full anesthesia. After cannulation, veno-arterial ECMO (V-A ECMO) was started 1 h after death and continued for 2 h under mild hypothermic conditions followed by organ harvest. Pressure- and flow-controlled oxygenated blood-based reperfusion of a cadaver body was accompanied by blood gas analysis (BGA), electrocardiography, and histological evaluation of ischemia-reperfusion injury. For the first time, we designed and implemented, a not yet reported, miniaturized murine hemodialysis circuit for the treatment of severe hyperkalemia and metabolic acidosis post-mortem., Results: BGA parameters confirmed profound ischemia typical for cadavers and incompatible with normal physiology, including extremely low blood pH, profound negative base excess, and enormously high levels of lactate. Two hours after ECMO implantation, blood pH values of a cadaver body restored from < 6.5 to 7.3 ± 0.05, pCO 2 was lowered from > 130 to 41.7 ± 10.5 mmHg, sO 2 , base excess, and HCO 3 were all elevated from below detection thresholds to 99.5 ± 0.6%, - 4 ± 6.2 and 22.0 ± 6.0 mmol/L, respectively (Student T test, p < 0.05). A substantial decrease in hyperlactatemia (from > 20 to 10.5 ± 1.7 mmol/L) and hyperkalemia (from > 9 to 6.9 ± 1.0 mmol/L) was observed when hemodialysis was implemented. On balance, the first signs of regained heart activity appeared on average 10 min after ECMO initiation without cardioplegia or any inotropic and vasopressor support. This was followed by restoration of myocardial contractility with a heart rate of up to 200 beats per minute (bpm) as detected by an electrocardiogram (ECG). Histological examinations revealed no evidence of heart injury 3 h post-mortem, whereas shock-specific morphological changes relevant to acute death and consequent cardiac/circulatory arrest were observed in the lungs, liver, and kidney of both control and ECMO-treated cadaver mice., Conclusions: Thus, our model represents a promising approach to facilitate studying perspectives of cadaveric multiorgan recovery for transplantation. Moreover, it opens new possibilities for cadaver organ treatment to extend and potentiate donation and, hence, contribute to solving the organ shortage dilemma., (© 2023. The Author(s).)

(1) Background: Implant-associated bacterial infections are usually hard to treat conservatively due to the resistance and tolerance of the pathogens to conventional antimicrobial therapy. Bacterial colonization of vascular grafts may lead to life-threatening conditions such as sepsis. The objective of this study is to evaluate whether conventional antibiotics and bacteriophages can reliably prevent the bacterial colonization of vascular grafts. (2) Methods: Gram-positive and Gram-negative bacterial infections were simulated on samples of woven PET gelatin-impregnated grafts using Staphylococcus aureus and Escherichia coli strains, respectively. The ability to prevent colonization was evaluated for a mixture of broad-spectrum antibiotics, for strictly lytic species-specific bacteriophage strains, and for a combination of both. All the antimicrobial agents were conventionally tested in order to prove the sensitivity of the used bacterial strains. Furthermore, the substances were used in a liquid form or in combination with a fibrin glue. (3) Results: Despite their strictly lytic nature, the application of bacteriophages alone was not enough to protect the graft samples from both bacteria. The singular application of antibiotics, both with and without fibrin glue, showed a protective effect against S. aureus (0 CFU/cm 2 ), but was not sufficient against E. coli without fibrin glue (M = 7.18 × 10 4 CFU/cm 2 ). In contrast, the application of a combination of antibiotics and phages showed complete eradication of both bacteria after a single inoculation. The fibrin glue hydrogel provided an increased protection against repetitive exposure to S. aureus ( p = 0.05). (4) Conclusions: The application of antibacterial combinations of antibiotics and bacteriophages is an effective approach to the prevention of bacteria-induced vascular graft infections in clinical settings.

Objective: An acute aortic dissection type A (AADA) is a rare but life-threatening event. The mortality rate ranges between 18% to 28% and mortality is often within the first 24 h and up to 1%-2% per hour. Although the onset of pain to surgery time has not been a relevant factor in terms of research in the field of AADA, we hypothesize that a patient's preoperative conditions depend on the length of this time., Methods: Between January 2000 and January 2018, 430 patients received surgical treatment for acute aortic dissection DeBakey type I at our tertiary referral hospital. In 11 patients, the exact time point of initial onset of pain was retrospectively not detectable. Accordingly, a total of 419 patients were included in the study. The cohort was categorized into two groups: Group A with an onset of pain to surgery time < 6 h ( n  = 211) and Group B > 6 h ( n  = 208), respectively., Results: Median age was 63.5 years (y) ((IQR: 53.3-71.4 y); (67.5% male)). Preoperative conditions differed significantly between the cohorts. Differences were detected in terms of malperfusion (A: 39.3%; B: 23.6%; P: 0.001), neurological symptoms (A: 24.2%; B: 15.4%; P: 0.024), and the dissection of supra-aortic arteries (A: 25.1%; B: 16.8%; P: 0.037). In particular, cerebral malperfusion (A 15.2%: B: 8.2%; P: 0.026) and limb malperfusion (A: 18%, B: 10.1%; P: 0.020) were significantly increased in Group A. Furthermore, Group A showed a decreased median survival time (A: 1,359.0 d; B: 2,247.5 d; P: 0.001), extended ventilation time (A: 53.0 h; B: 44.0 h; P: 0.249) and higher 30-day mortality rate (A: 25.1%; B: 17.3%; P: 0.051)., Conclusions: Patients with a short onset of pain to surgery time in cases of AADA present themselves not only with more severe preoperative symptoms but are also the more compromised cohort. Despite early presentation and emergency aortic repair, these patients show increased chances of early mortality. The "onset of pain to surgery time" should become a mandatory factor when making comparable surgical evaluations in the field of AADA., 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., (© 2023 Kaufeld, Martens, Beckmann, Rudolph, Krüger, Natanov, Arar, Korte, Schilling, Haverich and Shrestha.)

Objective: An acute type A aortic dissection (AAAD) is a critical emergency and remains one of the most challenging diseases in cardiothoracic surgery. The existence of a pericardial hematoma caused by an aortic rupture can dramatically reduce the chances of survival (Jerzewski and Kulik in J Card Surg 29(4):529-530, 2014; Mehta et al. in Circulation 105(2):200-206, 2002; Gilon et al. in Am J Cardiol 103(7):1029-1031, 2009; Isselbacher et al. in Circulation 90(5):2375-2378, 1994). We assessed the surgical outcome of a high-risk group of patients with AAAD and a pericardial hematoma., Methods: In this study we included 430 Patients (67% male; median age: 64 years) who received surgical treatment between January 2000 and January 2018 at our facility for acute aortic dissection DeBakey type I. We divided the cohort in two groups: Group A consisted of high-risk patients with a pericardial hematoma (n = 162) and Group B of patients without pericardial hematoma (n = 268)., Results: Patients with a preoperative pericardial hematoma had a significantly higher requirement for preoperative mechanical resuscitation (A: 21%; B: 1.5%; P: < 0.001) and were relevantly more frequently admitted to the operation theater with an intubated status (A: 19.8%; B: 8.6%; P: < 0.001). The incidence of visceral malperfusion differed significantly between both groups (A. 11.7%, B. 6:0%; P: 0.034). Limited aortic arch repair (proximal aortic arch replacement) was preferred in the high-risk group (A: 51.9%; B: 40.3%; P: 0.020). However, survival time was generally reduced in these patients (A: 7.5 y; B: 9.9 y)., Conclusion: AAAD patients with preoperative pericardial hematoma present themselves in potentially lethal conditions, with a significantly higher rate of visceral malperfusion. Despite the existence of this risk factor, a limited arch repair was favored. We have proven that cardiac compression is associated with preoperative intubation and mechanical resuscitation. Patients with pericardial hematoma must be further evaluated for preoperative pericardial drainage. In the event of long transfer times to an aortic center a slow drainage should be discussed to prevent early mortality., (© 2023. The Author(s).)

Towards the establishment of a long-term lung-assist device to be used both as a bridge and as an alternative to lung transplantation according to final destination therapy, we develop the biohybrid lung (BHL) on the technical basis of contemporary extracorporeal membrane oxygenation (ECMO). Here, to overcome the significant drawbacks of ECMO, in particular the missing hemocompatibility of the artificial surfaces, all blood-contacting areas need to be endothelialized sufficiently. In continuation of our recent accomplishments, demonstrating the feasibility of establishing a physiological acting endothelial cell (EC) monolayer on the hollow fiber membranes (HFMs) of the ECMO in vitro, the next step towards BHL translation is the endothelialization of the complete oxygenator, consisting of HFMs and the surrounding housing. Therefore, we assessed EC seeding inside our model oxygenator (MOx), which simulated the conditions in the assembled HFM oxygenators in order to identify the most important factors influencing efficient endothelialization, such as cell seeding density, cell distribution, incubation time and culture medium consumption. Overall, upon adjusting the concentration of infused ECs to 15.2 × 10 4 /cm 2 and ensuring optimal dispersion of cells in the MOx, viable and confluent EC monolayers formed on all relevant surfaces within 24 h, even though they comprised different polymers, i.e., the fibronectin-coated HFMs and the polysulfone MOx housing. Periodic medium change ensured monolayer survival and negligible apoptosis rates comparable to the reference within the assembled system. By means of these results, revealing essential implications for BHL development, their clinical translation is coming one step closer to reality.

Cell-free hemoglobin (CFH), a pro-oxidant and cytotoxic compound that is released in hemolysis, has been associated with nephrotoxicity. Lung transplantation (LuTx) is a clinical condition with a high incidence of acute kidney injury (AKI). In this study, we investigated the plasma levels of CFH and haptoglobin, a CFH-binding serum protein, in prospectively enrolled LuTx patients ( n = 20) with and without AKI. LuTx patients with postoperative AKI had higher CFH plasma levels at the end of surgery compared with no-AKI patients, and CFH correlated with serum creatinine at 48 h. Moreover, CFH levels inversely correlated with haptoglobin levels, which were significantly reduced at the end of surgery in LuTx patients with AKI. Because multiple other factors can contribute to AKI development in the complex clinical setting of LuTx, we next investigated the role of exogenous CFH administration in a mouse model of mild bilateral renal ischemia reperfusion injury (IRI). Exogenous administration of CFH after reperfusion caused overt AKI with creatinine increase, tubular injury, and enhanced markers of renal inflammation compared with vehicle-treated animals. In conclusion, CFH is a possible factor contributing to postoperative AKI after LuTx and promotes AKI in an experimental model of mild transient renal ischemia. Targeting CFH might be a therapeutic option to prevent AKI after LuTx.

Objective: Veno-venous (V-V) extracorporeal membrane oxygenation (ECMO) is increasingly used to support patients with severe acute respiratory distress syndrome (ARDS). In case of additional cardio-circulatory failure, some experienced centers upgrade the V-V ECMO with an additional arterial return cannula (termed V-VA ECMO). Here we analyzed short- and long-term outcome together with potential predictors of mortality., Design: Multicenter, retrospective analysis between January 2008 and September 2021., Setting: Three tertiary care ECMO centers in Germany (Hannover, Bonn) and Switzerland (Zurich)., Patients: Seventy-three V-V ECMO patients with ARDS and additional acute cardio-circulatory deterioration required an upgrade to V-VA ECMO were included in this study., Measurements and Main Results: Fifty-three patients required an upgrade from V-V to V-VA and 20 patients were directly triple cannulated. Median (Interquartile Range) age was 49 (28-57) years and SOFA score was 14 (12-17) at V-VA ECMO upgrade. Vasoactive-inotropic score decreased from 53 (12-123) at V-VA ECMO upgrade to 9 (3-37) after 24 h of V-VA ECMO support. Weaning from V-VA and V-V ECMO was successful in 47 (64%) and 40 (55%) patients, respectively. Duration of ECMO support was 12 (6-22) days and ICU length of stay was 32 (16-46) days. Overall ICU mortality was 48% and hospital mortality 51%. Two additional patients died after hospital discharge while the remaining patients survived up to two years (with six patients being lost to follow-up). The vast majority of patients was free from higher degree persistent organ dysfunction at follow-up. A SOFA score > 14 and higher lactate concentrations at the day of V-VA upgrade were independent predictors of mortality in the multivariate regression analysis., Conclusion: In this analysis, the use of V-VA ECMO in patients with ARDS and concomitant cardiocirculatory failure was associated with a hospital survival of about 50%, and most of these patients survived up to 2 years. A SOFA score > 14 and elevated lactate levels at the day of V-VA upgrade predict unfavorable outcome., 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 Erlebach, Wild, Seeliger, Rath, Andermatt, Hofmaenner, Schewe, Ganter, Müller, Putensen, Natanov, Kühn, Bauersachs, Welte, Hoeper, Wendel-Garcia, David, Bode and Stahl.)

The use of extracorporeal membrane oxygenation (ECMO) is associated with acute kidney injury (AKI) in thoracic organ transplantation. However, multiple other factors contribute to AKI development after these procedures such as renal ischemia-reperfusion injury (IRI) due to hypo-perfusion of the kidney during surgery. In this study, we aimed to explore the kidney injury patterns in mouse models of ECMO and renal IRI. Kidneys of C57BL/6 mice were examined after moderate (35 min) and severe (45 min) unilateral transient renal pedicle clamping and 2 h of veno-venous ECMO. Renal injury markers, neutrophil infiltration, tubular transport function, pro-inflammatory cytokines, and renal heme oxygenase-1 (HO-1) expression were determined by immunofluorescence and qPCR. Both procedures caused AKI, but with different injury patterns. Severe neutrophil infiltration of the kidney was evident after renal IRI, but not following ECMO. Tubular transport function was severely impaired after renal IRI, but preserved in the ECMO group. Both procedures caused upregulation of pro-inflammatory cytokines in the renal tissue, but with different time kinetics. After ECMO, but not IRI, HO-1 was strongly induced in tubular cells indicating contact with hemolysis-derived proteins. After IRI, HO-1 was expressed on infiltrating myeloid cells in the tubulo-interstitial space. In conclusion, renal IRI and ECMO both caused AKI, but kidney damage after renal IRI was more pronounced including severe neutrophil infiltration and tubular transport impairment. Enhanced HO-1 expression in tubular cells after ECMO encourages limitation of hemolysis as a therapeutic approach to reduce ECMO-associated AKI.

Objectives: To analyse whether full root replacement increases perioperative risks in patients who undergo frozen elephant trunk for acute aortic dissection., Methods: Between March 2013 and December 2019, 115 patients underwent emergency frozen elephant trunk for acute dissection. Patients without root replacement were assigned to group A, while patients with concomitant full root replacement to group B., Results: Mean age was 50.8 (12.5) years and 85 (73.9%) patients were male. Preoperative malperfusion was present in 49 (42.6%) patients. In group B, 27 (41.5%) patients received composite root replacement and 38 (33.0%) aortic valve-sparing David procedure. Cardiopulmonary-bypass and cross-clamp times were 252.5 (208.5-293.0) and 96.0 (40.5-148.0) min in group A, and 310.0 (274.0-346.5) and 121.0 (89.0-182.0) in group B (P < 0.001). Continuous myocardial perfusion was used in 40 (80.0%) patients of group A and 59 (90.8%) of group B (P = 0.098). Disabling stroke was present in 10 (20.0%) patients in group A and 12 (18.5%) in group B (P = 0.835). Thirty-day mortality was 12.0% (n = 6) in group A and 9.2% (n = 6) in group B (P = 0.630). The 1- and 5-year survival rates were 80% and 62% in group A, and 81% and 79% in group B. Logistic regression analysis identified age (odds ratio = 1.117, 95% confidence interval = 1.004-1.242, P = 0.041), cardiopulmonary-bypass time (odds ratio = 1.012, 95% confidence interval = 1.001-1.022, P = 0.029) and abdominal malperfusion (odds ratio = 17.394, 95% confidence interval = 2.030-149.013, P = 0.009) to be associated with 30-day mortality., Conclusions: Full root replacement does not increase the perioperative risk in patients who undergo frozen elephant trunk for acute dissection. Careful patient selection is important for such complex procedures. Continuous myocardial perfusion can help reducing the risk for intraoperative complications during such complex operations., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: Aortic valve-sparing root reimplantation (AVSRR) is a complex procedure, which offers the benefit of preserving the native aortic valve. Cardiac redo surgery is complex and time-consuming, and it is not known if David procedure is safe or beneficial in this context., Methods: Between 1993 and 2019, we performed a total of 544 elective AVSRR operations at our centre. Patients were assigned to either group A (n = 30, redo) or group B (n = 514, first-time sternotomy)., Results: Aortic cross-clamp time was higher in the redo group (173[62] vs 125[31], P < 0.001). Cardiopulmonary bypass time was higher in the redo group as well (250[78] vs 179[51], P < 0.001). There were significantly more concomitant total arch replacements in the redo group (43.3% vs 5.8%, P < 0.001) using the 'beating heart' technique (20.0% vs 1.9%, P < 0.001). In-hospital mortality was comparable in both groups (3.3% vs 1.8%, P = 0.44). The rates for perioperative complications in terms of permanent neurological deficit and rethoracotomy were comparable between the 2 groups, too. Follow-up was complete for 99.6% of all patients and comprised a total of 584 patient-years. The 1-, 5-, 10- and 15-year survival rates were 90%, 81%, 60% and 55%, in group A (redo) and 96%, 90%, 78% and 67% in group B (native, P = 0.16), respectively. The rates for freedom from valve-related reoperation at 1, 5, 10 and 15 years after initial surgery were 96%, 92%, 92% and 92% in group A (redo) and 97%, 92%, 87% and 84% in group B (native, P = 0.52), respectively., Conclusions: Despite significantly more concomitant total arch replacements in the redo group, early mortality was comparable in both groups. We conclude that AVSRR can be performed in redo cardiac surgery without compromising the early postoperative outcome. Careful patient assessment and selection are mandatory when evaluating patients with a history of previous cardiac surgery for David procedure., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Objectives: Cardiogenic shock is a life-threatening situation with high mortality rates. Mechanical unloading of the left ventricle may be achieved via left ventricular assist device (LVAD) implantation. Postoperative right ventricular (RV) failure, however, has very limited therapeutic options and is associated with increased postoperative mortality. In this paper, we describe a percutaneous right heart bypass for temporary postoperative RV support., Methods: We retrospectively examined all patients receiving percutaneous RV mechanical support after LVAD implantation. All patients receiving trans-jugular mechanical right heart bypass during or after LVAD implantation in our tertiary medical centre between November 2014 and December 2019 were examined retrospectively. The venous draining cannula was placed in the femoral vein; the pulmonary cannula was placed in the pulmonary artery using fluoroscopy., Results: In total, 14 patients received RV support using the trans-jugular technique. Mean age was 48.4 ± 14.9 years. Nine patients were treated with mechanical circulatory support before LVAD implantation. Biventricular support was done in 7 patients. All patients were treated with an Heartware HVAD . Mean postoperative intensive care unit stay was 46.3 ± 32.4 days. Mean right heart bypass support time was 10.6 ± 4.3 days. Twelve patients (86%) could be bridged to RV recovery, RV assist device implantation or heart transplantation., Conclusions: Percutaneous RV mechanical support is feasible, safe and shows acceptable outcome. Early implantation of RV support may contribute to successful outcome after LVAD implantation., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: Treatment of severe acute respiratory distress syndrome (ARDS) induced by severe acute respiratory syndrome coronavirus 2 has been heavily debated. Our goal was to describe our findings in patients with severe ARDS due to severe coronavirus disease 2019 (sCOVID-19) treated with venovenous extracorporeal membrane oxygenation (vv-ECMO)., Methods: We retrospectively examined all patients treated with vv-ECMO for severe ARDS due to acute respiratory syndrome coronavirus 2., Results: In total, 13 patients were treated with vv-ECMO in our medical centre. The mean patient age was 48.1 years. Most patients were obese (69%) and male (85%). All patients were mechanically ventilated before ECMO. The mean time from intubation to proning was 16.6 h; the time from start of prone therapy to vv-ECMO implantation was 155.1 h. The mean total ECMO run time was 358 h. Significant reduction of positive end-expiratory pressure (P = 0.02), peak pressure (P = 0.001) and minute volume (P = 0.03) could be achieved after implantation of vv-ECMO. All patients showed an inflammatory response. Overall mortality was 30.7%: 1 patient died of mesenteric ischaemia; 3 patients died of multiple organ failure. A worse prognosis was seen in patients with highly elevated concentrations of interleukin-6., Conclusions: The use of vv-ECMO in patients with sCOVID-19-induced ARDS is safe and associated with improved respiratory ventilation settings. The rate of immune system involvement plays a pivotal role in the development and outcome of sCOVID-19., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: Total aortic arch replacement is an invasive procedure with significant risks for complications. These risks are even higher in older, multimorbid patients. The current trends in demographic changes in western countries with an ageing population will aggravate this issue. In this study, we present our experience with total aortic arch replacement using the frozen elephant trunk (FET) technique in septuagenarians. We compared the results of septuagenarians with those of younger patients and analysed if there was an improvement in outcome over time., Methods: Between August 2001 and March 2020, 225 patients underwent non-urgent FET procedure at our institution. There were 75 patients aged ≥70 years (mean age 74 ± 4) who were assigned to group A, and 150 patients aged <70 years (mean age of 57 ± 11) who were assigned to group B. In groups A and B, the indications for surgery were chronic dissection (21% vs 53%), aortic aneurysm (78% vs 45%) and penetrating atherosclerotic ulcer (1% vs 2%)., Results: The rate for temporary dialysis was significantly higher in group A than in group B (29% vs 13%, P = 0.003), although the majority recovered kidney function. Rates for re-exploration for bleeding and stroke were comparable in both groups. In-hospital mortality was significantly higher in group A than in group B (24% vs 13%, P = 0.037). Logistic regression analysis showed that age >70 years was an independent statistically significant risk factor for in-hospital mortality (odds ratio = 2.513, 95% confidence interval = 1.197-5.278, P-value = 0.015). Follow-up was complete for 100% of patients and comprised a total of 1073 patient-years with a mean follow-up time of 4.8 ± 4.5 years. The 1- and 5-year survival rates were 68% and 49% in group A, and 85% and 71% in group B, respectively (log rank, P < 0.001). Survival did not significantly improve over time., Discussion: Total aortic arch replacement using the FET technique has a significantly higher risk for perioperative morbidity and mortality in septuagenarians than in younger patients. Long-term survival is significantly impaired in older patients. We recommend thorough patient selection of those who require total aortic arch replacement, and optimization of perioperative management to improve outcomes., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: Extracorporeal life support (ECLS) is an established tool to stabilize severely ill patients with therapy-refractory hemodynamic or respiratory failure. Recently, we established a mobile ECLS retrieval service at our institution. However, data on the outcome of patients receiving ECLS at outside hospitals for transportation into tertiary hospitals is still sparse., Methods: We have analyzed all patients receiving ECLS in outside hospitals (Transport group, TG) prior to transportation to our institution and compared the outcome to our in-house ECLS experience (Home Group, HG)., Results: Between 2012 and 2018, we performed 978 ECLS implantations, 243 of which were performed on-site in tertiary hospitals for ECLS supported transportation. Significantly more veno-venous systems were implanted in TG (n = 129 (53%) vs. n = 327 (45%), p = 0.012). Indication for ECLS support differed between the groups, with more pneumonia; acute respiratory distress syndromes in the TG group and of course, more postcardiotomy patients in HG. Mean age was 47 (± 20) (HG) vs. 48 (± 18) (TG) years, p = 0.477 with no change over time. No differences were seen in ECLS support time (8.03 days ±8.19 days HG vs 7.81 days ±6.71 days TG, p = 0.675). 30-day mortality (n = 379 (52%) (HG) vs. n = 119 (49%) (TG) p = 0.265) and death on ECLS support (n = 322 (44%) (HG) vs. n = 97 (40%) TG, p = 0.162) were comparable between the two groups, despite a more severe SAVE score in the v-a TG (HG: - 1.56 (± 4.73) vs. TG -3.93 (± 4.22) p < 0.001). Mortality rates did not change significantly over the years. Multivariate risk analysis revealed Influenza, Peak Insp. Pressure at implantation, pO2/FiO2 ratio and ECLS Score (SAVE/RESP) as well as ECLS support time to be independent risk factors for mortality., Conclusion: Mobile ECLS support is a tremendous challenge. However, it is justified to offer 24 h/7d ECLS standby for secondary and primary hospitals as a tertiary hospital. Increasing indications and total numbers for ECLS support raise the need for further studies to evaluate outcome in these patients.

Background: Improvement of single site cannulation for extracorporeal membrane oxygenation (ECMO) therapy is pivotal for reduction of patient morbidity and mortality in respiratory failure. To further improve the cardiopulmonary outcomes and reduce end organ damage, we established a murine model for single site cannulation with a double lumen cannula., Results: We created a hemodynamically stable double lumen cannula and successfully implanted it through the jugular vein into the upper and lower vena cava. This allowed adequate drainage of the blood. Blood gas analysis showed excellent oxygenation and CO 2 reduction. There was no excessive bleeding. No signs of right heart congestion were present which was confirmed in the histological analysis of the liver. Histology demonstrated moderate lung damage and mild acute kidney injury. Neutrophil infiltration was similar in ECMO and sham kidneys., Conclusions: Veno-venous extracorporeal circulation deteriorates kidney function and promotes moderate pulmonary damage.

Hypothermia is a treatment strategy for different clinical conditions and an essential part of cardiopulmonary bypass in complex cardiac procedures. Clinically, cooling patients is achieved via a mattress and heat exchanger integrated into a membrane oxygenator connected to a waterbed using a refrigerator system based on volatile and toxic liquids. Peltier elements are known as environmentally friendly thermoelectric generators that enable rapid warming and cooling. In this paper, we describe the construction of a novel device for rapid and precise control of mouse warming and cooling using thermoelectric Peltier elements. Six male BALB/c mice were subjected to deep hypothermia and were rewarmed under full physiological monitoring. After rewarming, all animals were observed for two hours, and pathology was evaluated in several organs. All animals tolerated the rapid cooling process well and remained active after rewarming. Temperature-relevant changes were seen via electrocardiography, with heart-rate patterns showing a strong linear correlation to body temperature. No myocardial ischaemia was seen. However, two animals experienced bradycardic atrial fibrillation which spontaneously converted to normal sinus rhythm during rewarming. No histological damage was seen in the heart, liver, kidney or lungs. Our device can effectively be used for heat shock and hypothermia studies in mice, and we foresee no obstacles for its application to other small rodents such as hamsters and young rats. In comparison to known experimental and clinical methods of hypothermia, our device is environmentally friendly, cost-effective and easy to handle, allowing precise control and maintenance of body temperatures ranging from 18℃ to 42℃.

The use of extracorporeal membrane oxygenation (ECMO) has increased substantially in recent years. ECMO has become a reliable and effective therapy for acute as well as end-stage lung diseases. With the increase in clinical demand and prolonged use of ECMO, procedural optimization and prevention of multi-organ damage are of critical importance. The aim of this protocol is to present a detailed technique of veno-venous ECMO in a non-intubated, spontaneously breathing mouse. This protocol demonstrates the technical design of the ECMO and surgical steps. This murine ECMO model will facilitate the study of pathophysiology related to ECMO (e.g., inflammation,bleeding and thromboembolic events). Due to the abundance of genetically modified mice, the molecular mechanisms involved in ECMO-related complications can also be dissected.

Cardiopulmonary bypass (CPB) with moderate hypothermic cardiac arrest (MHCA) is essential for prolonged complex procedures in cardiac surgery and is associated with postoperative complications. Although cytokine release provoked through MHCA under CPB plays a pivotal role in postoperative organ damage, the pathomechanisms are unclear. Here, we investigated the cytokine release pattern and histological organ damage after MHCA using a recently described mouse CPB model. Eight BALB/c mice underwent 60 minutes of circulatory arrest under CPB, were successively rewarmed and reperfused. Blood cytokine concentrations and liver and kidney function parameters were measured and histological changes to these organs were compared to control animals. Our results showed a marked increase in proinflammatory cytokines and histological changes in the kidney, lung, and liver after CPB. Furthermore, clinical chemistry showed signs of hemolysis and acute kidney injury. These results suggest early onset of solid organ injury which correlates with increased leukocyte infiltration. A better understanding of the interplay between pro-inflammatory cytokine activation and solid organ injury in this model of CBP with MHCA will inform strategies to reduce organ damage during cardiac surgeries in the clinic., Competing Interests: The authors have declared that no competing interests exist.

Objectives: Extracorporeal membrane oxygenation (ECMO) has an important role in bridging patients to lung transplantation. In this study, we present our experience with pretransplant ECMO during the last 7 years and investigate its impact on graft outcomes., Methods: Records of all lung-transplanted patients at our institution between January 2010 and April 2017 were retrospectively reviewed. Graft survival was compared between patients who required pretransplant ECMO (pre-Tx ECMO+) and patients who did not (pre-Tx ECMO-). Risk factors for in-hospital mortality and graft survival were identified using a binary logistic regression and the Cox regression analyses, respectively., Results: Among the 917 patients transplanted during the study period, 68 (7%) required ECMO as a bridge to transplantation [awake strategy, n = 57 (84%) patients]. Median bridging time was 9 days. Among pre-Tx ECMO+ patients, the need for haemodialysis at any point during bridging emerged as an independent risk factor for in-hospital mortality (odds ratio 7.79, 95% confidence interval 1.21-50.24; P = 0.031). Although in-hospital mortality was significantly higher in pre-Tx ECMO+ versus pre-Tx ECMO- patients (15% vs 5%, P = 0.003), overall graft survival did not differ between groups (79% vs 90% and 61% vs 68% at 1 and 5 years, respectively, P = 0.13). Pretransplant ECMO did not emerge as a risk factor for graft survival in the multivariable analysis., Conclusions: If applied in selected patients in a high-volume centre, pretransplant ECMO as a bridge to transplantation results in impaired, but still high in-hospital, survival and does not impact graft survival.

Objectives: Cardiopulmonary bypass (CPB) is an essential component of many cardiac interventions, and therefore, there is an increasing critical demand to minimize organ damage resulting from prolonged extracorporeal circulation. Our goal was to develop the first clinically relevant mouse model of CPB and to examine the course of extracorporeal circulation by closely monitoring haemodynamic and oxygenation parameters., Methods: Here, we report the optimization of device design, perfusion circuit and microsurgical techniques as well as validation of physiological functions during CPB in mice after circulatory arrest and reperfusion. Validation of the model required multiple blood gas analyses, and therefore, this initial report describes an acute model that is incompatible with survival due to the need of repetitive blood draws., Results: Biochemical and histopathological assessment of organ damage revealed only mild changes in the heart and lungs and signs of the beginning of acute organ failure in the liver and kidneys., Conclusions: This new CPB mouse model will facilitate preclinical testing of therapeutic strategies in cardiovascular diseases and investigation of CPB in relation to different insults and pre-existing comorbidities. In combination with genetically modified mice, this model will be an important tool to dissect the molecular mechanisms involved in organ damage related to extracorporeal circulation., (© The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

As prolonged cardiopulmonary bypass becomes more essential during cardiac interventions, an increasing clinical demand arises for procedure optimization and for minimizing organ damage resulting from prolonged extracorporal circulation. The goal of this paper was to demonstrate a fully functional and clinically relevant model of cardiopulmonary bypass in a mouse. We report on the device design, perfusion circuit optimization, and microsurgical techniques. This model is an acute model, which is not compatible with survival due to the need for multiple blood drawings. Because of the range of tools available for mice (e.g., markers, knockouts, etc.), this model will facilitate investigation into the molecular mechanisms of organ damage and the effect of cardiopulmonary bypass in relation to other comorbidities.

Nonclassical HLAs, HLA-E and HLA-G, are known to affect clinical outcome in various tumor types. We examined the clinical impact of HLA-E and HLA-G expression in early breast cancer patients, and related the results to tumor expression of classical HLA class I. Our study population (n = 677) consisted of all early breast cancer patients primarily treated with surgery in our center between 1985 and 1995. Tissue microarray sections of arrayed tumor and normal control material were immunohistochemically stained for HLA-E and HLA-G. For evaluation of HLA-E and HLA-G and the combined variable, HLA-EG, a binary score was used. Expression of classical HLA class I molecules was determined previously. HLA-E, HLA-G, and HLA-EG on breast tumors were classified as expression in 50, 60, and 23% of patients, respectively. Remarkably, only in patients with loss of classical HLA class I tumor expression, expression of HLA-E (p = 0.027), HLA-G (p = 0.035), or HLA-EG (p = 0.001) resulted in a worse relapse-free period. An interaction was found between classical and nonclassical HLA class I expression (p = 0.002), suggestive for a biological connection. We have demonstrated that, next to expression of classical HLA class I, expression of HLA-E and HLA-G is an important factor in the prediction of outcome of breast cancer patients. These results provide further evidence that breast cancer is immunogenic, but also capable of evading tumor eradication by the host's immune system, by up- or downregulation of HLA class Ia and class Ib loci.