Hypoxic perfusion of pulmonary arterial vasa vasorum increases pulmonary arterial pressure.

The pathophysiology of pulmonary hypertension (PH) is not fully understood. Here, we tested the hypothesis that hypoxic perfusion of the vasa vasorum of the pulmonary arterial (PA) wall causes PH. Young adult pig lungs were explanted and placed into a modified ex vivo lung perfusion unit (Organ care system, OCS) allowing the separate adjustment of parameters for mechanical ventilation, as well as PA perfusion and bronchial arterial (BA) perfusion. PA vasa vasorum are branches of the BA. The lungs were used either as control (n=3) or intervention group (n=8). The protocol of the intervention group was as follows: normoxic ventilation and perfusion (steady state) -hypoxic BA perfusion -steady state -hypoxic BA perfusion. During hypoxic BA perfusion, ventilation and PA perfusion maintained normal. Control lungs were kept under steady state conditions for 105 minutes. During the experiments, PA pressure (PAP) and blood gas analysis was frequently monitored. Hypoxic perfusion of the BA resulted in an increase in systolic and mean PAP, a reaction that was reversible upon normoxic BA perfusion. The PAP increase was reproducible in the second hypoxic BA perfusion. Under control conditions the PAP stayed constant until about 80 minutes of the experiment. In conclusion, the results of the current study prove that hypoxic perfusion of the vasa vasorum of the PA directly increases PAP in an ex situ lung perfusion setup suggesting that PA vasa vasorum function and wall ischemia may contribute to the development of PH.

Five-year results from a prospective, single-arm European trial on decellularized allografts for aortic valve replacement-the ARISE Study and ARISE Registry Data.

OBJECTIVES: Decellularized aortic homografts (DAH) were introduced as a new option for aortic valve replacement for young patients. METHODS: A prospective, EU-funded, single-arm, multicentre study in 8 centres evaluating non-cryopreserved DAH for aortic valve replacement. RESULTS: A total of 144 patients (99 male) were prospectively enrolled in the ARISE Trial between October 2015 and October 2018 with a median age of 30.4 years [interquartile range (IQR) 15.9-55.1]; 45% had undergone previous cardiac operations, with 19% having 2 or more previous procedures. The mean implanted DAH diameter was 22.6 mm (standard deviation 2.4). The median operation duration was 312 min (IQR 234-417), the median cardiopulmonary bypass time was 154 min (IQR 118-212) and the median cross-clamp time 121 min (IQR 93-150). No postoperative bypass grafting or renal replacement therapy were required. Two early deaths occurred, 1 due to a LCA thrombus on day 3 and 1 due ventricular arrhythmia 5 h postoperation. There were 3 late deaths, 1 death due to endocarditis 4 months postoperatively and 2 unrelated deaths after 5 and 7 years due to cancer and Morbus Wegener resulting in a total mortality of 3.47%. After a median follow-up of 5.9 years [IQR 5.1-6.4, mean 5.5 years. (standard deviation 1.3) max. 7.6 years], the primary efficacy end-points peak gradient with median 11.0 mmHg (IQR 7.8-17.6) and regurgitation of median 0.5 (IQR 0-0.5) of grade 0-3 were excellent. At 5 years, freedom from death/reoperation/endocarditis/bleeding/thromboembolism were 97.9%/93.5%/96.4%/99.2%/99.3%, respectively. CONCLUSIONS: The 5-year results of the prospective multicentre ARISE trial continue to show DAH to be safe for aortic valve replacement with excellent haemodynamics.

Public controversy and citizens' attitude formation about animal research: A case for scholarship and recommendations on conflicts at the science-society interface.

Activist groups attack animal research and put scientists and their institutions under pressure, whereas scientists often remain silent. We report an interdisciplinary research project driven by a communication science perspective on how citizens respond to news reports about animal research (3 experiments, overall N = 765) and a German science-initiated information platform ("Tierversuche verstehen"; controlled user study, N = 100). Findings demonstrate that a critical journalist perspective within neutral, two-sided news reports (e.g., skeptical expert statements or images of suffering animals) does not affect citizen opinion strongly. Information media provided by scientific institutions seem to be welcomed even by citizens who hold critical prior attitudes. From these results, we develop a set of recommendations for future public communication of animal research that builds on best practices in organizational and crisis communication. These suggestions are intended to empower animal researchers to actively participate in public debate to support citizens' informed attitude formation.

Matched comparison of decellularized homografts and bovine jugular vein conduits for pulmonary valve replacement in congenital heart disease.

For decades, bovine jugular vein conduits (BJV) and classic cryopreserved homografts have been the two most widely used options for pulmonary valve replacement (PVR) in congenital heart disease. More recently, decellularized pulmonary homografts (DPH) have provided an alternative avenue for PVR. Matched comparison of patients who received DPH for PVR with patients who received bovine jugular vein conduits (BJV) considering patient age group, type of heart defect, and previous procedures. 319 DPH patients were matched to 319 BJV patients; the mean age of BJV patients was 15.3 (SD 9.5) years versus 19.1 (12.4) years in DPH patients (p = 0.001). The mean conduit diameter was 24.5 (3.5) mm for DPH and 20.3 (2.5) mm for BJV (p < 0.001). There was no difference in survival rates between the two groups after 10 years (97.0 vs. 98.1%, p = 0.45). The rate of freedom from endocarditis was significantly lower for BJV patients (87.1 vs. 96.5%, p = 0.006). Freedom from explantation was significantly lower for BJV at 10 years (81.7 vs. 95.5%, p = 0.001) as well as freedom from any significant degeneration at 10 years (39.6 vs. 65.4%, p < 0.001). 140 Patients, matched for age, heart defect type, prior procedures, and conduit sizes of 20-22 mm (± 2 mm), were compared separately; mean age BJV 8.7 (4.9) and DPH 9.5 (7.3) years (p = n.s.). DPH showed 20% higher freedom from explantation and degeneration in this subgroup (p = 0.232). Decellularized pulmonary homografts exhibit superior 10-year results to bovine jugular vein conduits in PVR.

Mechano-chemo-biological model of atherosclerosis formation based on the outside-in theory.

Atherosclerosis is a disease in blood vessels that often results in plaque formation and lumen narrowing. It is an inflammatory response of the tissue caused by disruptions in the vessel wall nourishment. Blood vessels are nourished by nutrients originating from the blood of the lumen. In medium-sized and larger vessels, nutrients are additionally provided from outside through a network of capillaries called vasa vasorum. It has recently been hypothesized (Haverich in Circulation 135:205-207, 2017) that the root of atherosclerotic diseases is the malfunction of the vasa vasorum. This, so-called outside-in theory, is supported by a recently developed numerical model (Soleimani et al. in Arch Comput Methods Eng 28:4263-4282, 2021) accounting for the inflammation initiation in the adventitial layer of the blood vessel. Building on the previous findings, this work proposes an extended material model for atherosclerosis formation that is based on the outside-in theory. Beside the description of growth kinematics and nutrient diffusion, the roles of monocytes, macrophages, foam cells, smooth muscle cells and collagen are accounted for in a nonlinear continuum mechanics framework. Cells are activated due to a lack of vessel wall nourishment and proliferate, migrate, differentiate and synthesize collagen, leading to the formation of a plaque. Numerical studies show that the onset of atherosclerosis can qualitatively be reproduced and back the new theory.

Acute Aortic Dissection Type A in Younger Patients (< 60 Years Old) - Does Full Arch Replacement Provide Benefits Compared to Limited Approach?

ABSTRACT 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.

CD14highCD16+ monocytes are the main producers of Interleukin-10 following clinical heart transplantation.

Introduction: Following heart transplantation, a cascade of immunological responses is initiated influencing the clinical outcome and long-term survival of the transplanted patients. The anti-inflammatory cytokine interleukin-10 (IL-10) was shown to be elevated in the blood of heart transplant recipients directly after transplantation but the releasing cell populations and the composition of lymphocyte subsets following transplantation have not been thoroughly studied. Methods: We identified immune cells by immunophenotyping and analyzed intracellular IL-10 production in peripheral blood mononuclear cells (PBMC) of heart transplanted patients (n= 17) before, directly after and 24h post heart transplantation. The cells were stimulated with lipopolysaccharide or PMA/Ionomycin to enhance cytokine production within leukocytes in vitro. Results and discussion: We demonstrate that intermediate monocytes (CD14highCD16+), but not CD8+ T cells, CD4+ T cells, CD56+ NK cells or CD20+ B cells appeared to be the major IL-10 producers within patients PBMC following heart transplantation. Consequently, the absolute monocyte count and the ratio of intermediate monocytes to classical monocytes (CD14+CD16-) were specifically increased in comparison to pre transplant levels. Hence, this population of monocytes, which has not been in the focus of heart transplantation so far, may be an important modulator of clinical outcome and long-term survival of heart transplant recipients. Alteration of blood-circulating monocytes towards a CD14highCD16+ phenotype could therefore shift the pro-inflammatory immune response towards induction of graft tolerance, and may pave the way for the optimization of immunosuppression.

Acute Aortic Dissection Type A in Younger Patients (< 60 Years Old) - Does Full Arch Replacement Provide Benefits Compared to Limited Approach?

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.

Development, comparative structural analysis, and first in vivo evaluation of acellular implanted highly compacted fibrin tubes for arterial bypass grafting.

The generation of small-caliber vascular grafts remains a significant challenge within the field of tissue engineering. In pursuit of this objective, fibrin has emerged as a promising scaffold material. However, its lack of biomechanical strength has limited its utility in the construction of tissue engineered vascular grafts. We have previously reported about the implementation of centrifugal casting molding to generate compacted fibrin tubes with a highly increased biomechanical strength. In this study, we conducted a structural analysis of compacted fibrin tubes using the open-source software Fiji/BoneJ. The primary aim was to validate the hypothesis that the compaction of fibrin leads to a more complex structure characterized by increased crosslinking of fibrin fibers. Structural analysis revealed a strong correlation between fibrin's structure and its biomechanical strength. Moreover, we enhanced fibrin compaction in a subsequent dehydration process, leading to a significant increase of biomechanical strength. Thus, the presented method in combination with an adequate imaging, e.g., micro-CT, has substantial potential as a powerful tool for quality assurance in the development of fibrin-based vascular grafts. To validate this concept, acellular highly compacted fibrin tubes were implanted as substitutes of a segment of the carotid artery in a sheep model (n = 4). After 6 months explanted segments exhibited distinct remodeling, transitioning into newly formed arteries.

Interplay between driveline infection, vessel wall inflammation, cerebrovascular events and mortality in patients with left ventricular assist device.

In patients with left ventricular assist device (LVAD), infections and thrombotic events represent severe complications. We investigated device-specific local and systemic inflammation and its impact on cerebrovascular events (CVE) and mortality. In 118 LVAD patients referred for 18F-FDG-PET/CT, metabolic activity of LVAD components, thoracic aortic wall, lymphoid and hematopoietic organs, was quantified and correlated with clinical characteristics, laboratory findings, and outcome. Driveline infection was detected in 92/118 (78%) patients by 18F-FDG-PET/CT. Activity at the driveline entry site was associated with increased signals in aortic wall (r = 0.32, p < 0.001), spleen (r = 0.20, p = 0.03) and bone marrow (r = 0.20, p = 0.03), indicating systemic interactions. Multivariable analysis revealed independent associations of aortic wall activity with activity of spleen (ß = 0.43, 95% CI 0.18-0.68, p < 0.001) and driveline entry site (ß = 0.04, 95% CI 0.01-0.06, p = 0.001). Twenty-two (19%) patients suffered CVE after PET/CT. In a binary logistic regression analysis metabolic activity at the driveline entry site missed the level of significance as an influencing factor for CVE after adjusting for anticoagulation (OR = 1.16, 95% CI 1-1.33, p = 0.05). Metabolic activity of the subcutaneous driveline (OR = 1.13, 95% CI 1.02-1.24, p = 0.016) emerged as independent risk factor for mortality. Molecular imaging revealed systemic inflammatory interplay between thoracic aorta, hematopoietic organs, and infected device components in LVAD patients, the latter predicting CVE and mortality.

Free heme and hemopexin in acute kidney injury after cardiopulmonary bypass and transient renal ischemia.

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.

Pushing the boundaries of innovation: the potential of ex vivo organ perfusion from an interdisciplinary point of view.

Ex vivo machine perfusion (EVMP) is an emerging technique for preserving explanted solid organs with primary application in allogeneic organ transplantation. EVMP has been established as an alternative to the standard of care static-cold preservation, allowing for prolonged preservation and real-time monitoring of organ quality while reducing/preventing ischemia-reperfusion injury. Moreover, it has paved the way to involve expanded criteria donors, e.g., after circulatory death, thus expanding the donor organ pool. Ongoing improvements in EVMP protocols, especially expanding the duration of preservation, paved the way for its broader application, in particular for reconditioning and modification of diseased organs and tumor and infection therapies and regenerative approaches. Moreover, implementing EVMP for in vivo-like preclinical studies improving disease modeling raises significant interest, while providing an ideal interface for bioengineering and genetic manipulation. These approaches can be applied not only in an allogeneic and xenogeneic transplant setting but also in an autologous setting, where patients can be on temporary organ support while the diseased organs are treated ex vivo, followed by reimplantation of the cured organ. This review provides a comprehensive overview of the differences and similarities in abdominal (kidney and liver) and thoracic (lung and heart) EVMP, focusing on the organ-specific components and preservation techniques, specifically on the composition of perfusion solutions and their supplements and perfusion temperatures and flow conditions. Novel treatment opportunities beyond organ transplantation and limitations of abdominal and thoracic EVMP are delineated to identify complementary interdisciplinary approaches for the application and development of this technique.

Mathematical modeling and numerical simulation of arterial dissection based on a novel surgeon's view.

This paper presents a mathematical model for arterial dissection based on a novel hypothesis proposed by a surgeon, Axel Haverich, see Haverich (Circulation 135(3):205-207, 2017. https://doi.org/10.1161/circulationaha.116.025407 ). In an attempt and based on clinical observations, he explained how three different arterial diseases, namely atherosclerosis, aneurysm and dissection have the same root in malfunctioning Vasa Vasorums (VVs) which are micro capillaries responsible for artery wall nourishment. The authors already proposed a mathematical framework for the modeling of atherosclerosis which is the thickening of the artery walls due to an inflammatory response to VVs dysfunction. A multiphysics model based on a phase-field approach coupled with mechanical deformation was proposed for this purpose. The kinematics of mechanical deformation was described using finite strain theory. The entire model is three-dimensional and fully based on a macroscopic continuum description. The objective here is to extend that model by incorporating a damage mechanism in order to capture the tearing (rupture) in the artery wall as a result of micro-injuries in VV. Unlike the existing damage-based model of the dissection in the literature, here the damage is driven by the internal bleeding (hematoma) rather than purely mechanical external loading. The numerical implementation is carried out using finite element method (FEM).

Heart Transplantation in High-Risk Recipients Employing Donor Marginal Grafts Preserved With Ex-Vivo Perfusion.

Extending selection criteria to face donor organ shortage in heart transplantation (HTx) may increase the risk of mortality. Ex-vivo normothermic perfusion (EVP) limits ischemic time allowing assessment of graft function. We investigated the outcome of HTx in 80 high-risk recipients transplanted with marginal donor and EVP-preserved grafts, from 2016 to 2021. The recipients median age was 57 years (range, 13-75), with chronic renal failure in 61%, impaired liver function in 11% and previous cardiac surgery in 90%; 80% were mechanically supported. Median RADIAL score was 3. Mean graft ischemic time was 118 ± 25 min, "out-of-body" time 420 ± 66 min and median cardiopulmonary bypass (CPB) time 228 min (126-416). In-hospital mortality was 11% and ≥moderate primary graft dysfunction 16%. At univariable analysis, CPB time and high central venous pressure were risk factors for mortality. Actuarial survival at 1 and 3 years was 83% ± 4%, and 72% ± 7%, with a median follow-up of 16 months (range 2-43). Recipient and donor ages, pre-HTx extracorporeal life support and intra-aortic balloon pump were risk factors for late mortality. In conclusion, the use of EVP allows extension of the graft pool by recruitment of marginal donors to successfully perform HTx even in high-risk recipients.

Lungs From Donors ≥70 Years of Age for Transplantation-Do Long-Term Outcomes Justify Their Use?

Donor shortages have led transplant centers to extend their criteria for lung donors. Accepting lung donors ≥70 years of age has previously shown good short-term outcomes; however, no mid- and long-term outcome data on these extended criteria donors has been published to date. In this study, all patients who underwent lung transplantation between 06/2010 and 12/2019 were included in the analysis, and the outcomes were compared between patients receiving organs from donors <70 years of age and patients transplanted with lungs from donors ≥70 years of age. Among the 1,168 lung-transplanted patients, 62 patients received lungs from donors ≥70 years of age. The recipient age of those receiving older organs was significantly higher, and they were more likely to suffer from obstructive lung disease. Older donors were exposed to significantly shorter periods of mechanical ventilation prior to donation, had higher Horowitz indices, and were less likely to have smoked. The postoperative time on mechanical ventilation, time on ICU, and total hospital stay were comparable. The overall survival as well as CLAD-free survival showed no differences between both groups in the follow-up period. Utilization of lungs from donors ≥70 years of age leads to excellent mid- and long-term results that are similar to organs from younger donors when the organs from older donors are carefully preselected.

Genetic knockout of porcine GGTA1 or CMAH/GGTA1 is associated with the emergence of neo-glycans.

BACKGROUND: Pig-derived tissues could overcome the shortage of human donor organs in transplantation. However, the glycans with terminal α-Gal and Neu5Gc, which are synthesized by enzymes, encoded by the genes GGTA1 and CMAH, are known to play a major role in immunogenicity of porcine tissue, ultimately leading to xenograft rejection. METHODS: The N-glycome and glycosphingolipidome of native and decellularized porcine pericardia from wildtype (WT), GGTA1-KO and GGTA1/CMAH-KO pigs were analyzed by multiplexed capillary gel electrophoresis coupled to laser-induced fluorescence detection. RESULTS: We identified biantennary and core-fucosylated N-glycans terminating with immunogenic α-Gal- and α-Gal-/Neu5Gc-epitopes on pericardium of WT pigs that were absent in GGTA1 and GGTA1/CMAH-KO pigs, respectively. Levels of N-glycans terminating with galactose bound in ß(1-4)-linkage to N-acetylglucosamine and their derivatives elongated by Neu5Ac were increased in both KO groups. N-glycans capped with Neu5Gc were increased in GGTA1-KO pigs compared to WT, but were not detected in GGTA1/CMAH-KO pigs. Similarly, the ganglioside Neu5Gc-GM3 was found in WT and GGTA1-KO but not in GGTA1/CMAH-KO pigs. The applied detergent based decellularization efficiently removed GSL glycans. CONCLUSION: Genetic deletion of GGTA1 or GGTA1/CMAH removes specific epitopes providing a more human-like glycosylation pattern, but at the same time changes distribution and levels of other porcine glycans that are potentially immunogenic.

Impact of total ischaemic time and disease severity class on graft function after bilateral lung transplantation.

OBJECTIVES: Total ischaemic time (IT) is considered a limiting factor in lung transplantation. In this retrospective study, we investigate effects of IT and disease burden on outcomes after bilateral lung transplantation. METHODS: A total of 1298 patients undergoing bilateral lung transplantation between January 2010 and May 2022 (follow-up 100%, median 54 months) were included. Pre-transplant diseases' severity (recipient body mass index, recipient age, previous lung transplantation, Tacrolimus immunosuppression, preoperative recipient extracorporeal membrane oxygenation support, lung volume reduction) for graft failure was individually calculated and-as IT-categorized. Vice versa adjusted Cox models were calculated. Considering competing risks, we assessed cumulative incidences of airway obstructive complications and chronic lung allograft dysfunction with death as competing risk factors for primary graft dysfunction were assessed by binary logistic regression. RESULTS: Higher disease burden significantly accelerated chronic lung allograft dysfunction and death occurrence (P < 0.001); IT did not. IT-adjusted disease burden strata showed 50% graft survival differences at 11 years after transplantation (range 24-74%), disease burden-adjusted IT strata 18% for all and 6% (54-60%) among those above 7 h. All significant primary graft dysfunction risk factors were diagnoses related, IT was not significantly important and odds ratios did not increase with IT. CONCLUSIONS: The eventual graft survival disadvantage that results from an IT between 7 and at least 11 h is negligible in contrast to frequent recipients' disease-based risk levels.

Onset of pain to surgery time in acute aortic dissections type A: a mandatory factor for evaluating surgical results?

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.

Combination of Bacteriophages and Antibiotics for Prevention of Vascular Graft Infections-An In Vitro Study.

(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/cm2), but was not sufficient against E. coli without fibrin glue (M = 7.18 × 104 CFU/cm2). 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.