Bleeding and thrombotic complications and their impact on mortality in patients supported with left ventricular assist device for cardiogenic shock.

INTRODUCTION: Thrombosis and bleeding are major complications in patients supported with left ventricular assist devices (LVADs). We aimed to assess the incidence of bleeding and thrombosis in patients supported with a HeartWare left ventricular assist device (HVAD), their predictive factors and their impact on mortality. METHODS: A single centre retrospective observational study of patients supported with HVAD over 5 years from January 2015 to October 2020. RESULTS: A total 139 patients (median age 52.5, 72.1% male) were included for analysis. The probability of 1-year survival was 73.1%. Advanced age (>60 years) and EuroSCORE II score (>20%) were independently associated with reduced survival. Major bleeding and thrombosis occurred in 46.8% and 35.3% respectively. Secondary mechanical circulatory support (MCS) increased likelihood of experiencing major bleeding (HR: 2.76, 95%1.65-4.62, p < 0.0001) whilst patients receiving aspirin were protected from bleeding and thrombosis (HR: 0.34 95% CI 0.19-0.58, p < 0.001). Pre-operative anaemia (HR: 3.02, 95% CI: 1.6-5.7, p = 0.014) and use of a secondary MCS device (HR: 2.78, 95% CI: 1.2-6.3, p = 0.001) were associated with an increased risk of thrombosis. Patients with any major bleeding (with or without thrombosis) had a 7.68-fold (95% CI 3.5-16.8) increased risk of death compared to those without. In contrast, 'thrombosis only' patients had 4.23-fold (95% CI 1.8-10.2) increased risk of death compared to those without thrombosis. The risk of mortality was increased in patients with any thrombosis and the risk of death was highest in patients with major bleeding and thrombosis (HR: 16.49 [95% CI 7.7-35.3]). CONCLUSIONS: Major bleeding and thrombosis significantly increase the 1-year mortality. Optimal perioperative haemostasis and anticoagulation remains crucial in patients supported with HVAD.

Postoperative acute kidney injury and renal replacement therapy after DCD lung transplantation.

Acute kidney injury (AKI) after lung transplantation (LTx) is a common complication. We aimed to assess whether donation after circulatory death (DCD) is associated with an increased risk of AKI and renal replacement therapy (RRT) in the early postoperative period compared to the donation after brain death (DBD). Retrospective data on a cohort (N = 95) of LTx patients (DCD n = 17, DBD n = 78) characterized by no use of ex-vivo lung perfusion were analyzed for the incidence of AKI within 30 postoperative days and incidence of RRT within 7 and 30 days. After optimal full matching, an imbalance remained between the DCD and DBD patients in respect to intraoperative use of cardiopulmonary bypass (CPB). Therefore, a further subset (n = 77) was defined that excluded CPB patients, and matching was repeated (DCD n = 13 vs. DBD n = 63) resulting in a fair balance on a range of preoperative characteristics and intraoperative use of ECMO. In both matched subsets, DCD was associated with around twice higher risk of AKI and RRT within 7 and 30 postoperative days. In conclusion, data suggest that DCD could be associated with worse early renal outcomes in a subset of LTx patients and justify further studies on the topic in order to refine further renal care pathways perioperatively.

Midterm outcomes of venovenous extracorporeal membrane oxygenation as a bridge to lung transplantation: Comparison with nonbridged recipients.

OBJECTIVES: Venovenous extracorporeal membrane oxygenation (VV-ECMO) is increasingly being used in acutely deteriorating patients with end-stage lung disease as a bridge to transplantation (BTT). It can allow critically ill recipients to remain eligible for lung transplants (LTx) while reducing pretransplant deconditioning. We analyzed early- and midterm postoperative outcomes of patients on VV-ECMO as a BTT and the impact of preoperative VV-ECMO on posttransplant survival outcomes. METHODS: All consecutive LTx performed at our institution between January 2012 and December 2018 were analyzed. After matching, BTT patients were compared with nonbridged LTx recipients. RESULTS: Out of 297 transplanted patients, 21 (7.1%) were placed on VV-ECMO as a BTT. After matching, we observed similar 30-day mortality between BTT and non-BTT patients (4.6% vs. 6.6%, p = .083) despite a higher incidence of early postoperative complications (need for ECMO, delayed chest closure, and acute kidney injury). Furthermore, preoperative VV-ECMO did not appear associated with 30-day or 1-year mortality in both frequentist and Bayesian analysis (odds ratio [OR]: 0.35, 95% confidence interval: 0.03-3.49, p = .369; OR: 0.27, 95% credible interval: 0.01-3.82, p = 84.7%, respectively). In sensitivity analysis, both subgroups were similar in respect to 30-day (7.8% vs. 6.5%, p = .048) and 1-year mortality (12.5% vs. 18%, p = .154). CONCLUSIONS: Patients with acute refractory respiratory failure while waiting for LTx represent a high-risk cohort of patients. VV-ECMO as a BTT is a reasonable strategy in adult patients with acceptable operative mortality and 1-year survival comparable to non-BTT patients.

Outcomes of heart transplantation in patients bridged with Impella 5.0: Comparison with native chest transplanted patients without preoperative mechanical circulatory support.

The Impella (Abiomed, Danvers, MA, USA) has become an important adjunct treatment modality in bridging patients with end-stage heart failure to recovery or orthotopic heart transplantation (HTx). We compared the outcome of patients directly bridged to HTx with the Impella 5.0 versus patients without mechanical circulatory support (MCS). Patients with no previous sternotomy or MCS, who were transplanted between September 2014 and March 2019 were included in this retrospective analysis. Impella 5.0 was implanted using surgical access and transesophageal echocardiography guidance. Forty-two out of 155 transplanted patients fulfilled the insertion criteria. Eight (19%) were bridged with Impella 5.0 to HTx. Recipient and donor baseline characteristics were comparable in both groups. There were no significant differences in survival between the groups at 30-day (94% no MCS vs. 87.5% Impella group, P = .47) or 6 months (94% vs. 87.5%, P = .51). Patients on Impella 5.0 showed a significant recovery of hemodynamic parameters and end-organ function. Average duration of support to HTx was 16 ± 17 days. Impella 5.0, when used in suitable patients in a timely fashion can be a good strategy for bridging patients to HTx. The axillary approach allows for early extubation and mobilization. Outcomes of patients bridged to HTx with Impella 5.0 in acute cardiogenic shock are comparable to those of patients with no MCS.

Use of oxygenator with short-term ventricular assist devices.

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) serves as a conventional short-term mechanical circulatory assist to support heart and lung functions. The short-term ventricular assist devices (ST-VAD) can, on the contrary, offer only circulatory support. A combination of VAD and oxygenator (Oxy-VAD) could help overcome this potential disadvantage. This is a retrospective case note study of patients supported on ST-VAD which required adding an oxygenator for extra respiratory support. The oxygenator was introduced in the ST-VAD circuit, either on the left or the right side. Twenty-two patients with the etiology of refractory cardiogenic shock in decompensation were supported on Oxy-VAD between years 2009 and 2019 at tertiary care . All patients were classified into class-I INTERMACS with a mean SOFA Score of 14 ± 2.58. 86.4% of patients were already on mechanical support pre-ST-VAD implant, 80% on VA-ECMO. The BiVAD implant accounted for 63.6%, followed by LVAD and RVAD with 27.3% and 9.1%. Mean duration of the ST-VAD was 8.5 days. The oxygenator was introduced in 14 RVAD and 8 LVAD circuits. The oxygenator was successfully weaned in 54.5% while ST-VAD was explanted in 31.8%. Discharge to home survival was 22.7%. Oxy-VAD proves a viable, and probably, a better option to VA-ECMO in acute cardiorespiratory decompensation. It offers organ-specific tailor-made support to the right and/or left heart and/or lungs. While on Oxy-VAD support, each organ performance can be assessed independently, and the assistance of the specifically improved organ can be weaned off without discontinuing the support for the rest.

Valvular complications following the Impella device implantation.

BACKGROUND: Despite clear clinical benefits, there is limited evidence regarding possible complications of the novel mechanical support device Impella. Aortic and mitral valve regurgitation or injury are rare but potential complications following implantation of the Impella device. METHODS: To evaluate valvular complications after the Impella device implantation, we have performed a comprehensive search of literature on multiple sites on this topic. RESULTS AND CONCLUSION: Ten case reports and one observational retrospective study were identified, with a total number of 19 patients identified. This article aims to draw attention to potential periprocedural complications relating to the Impella, in particular iatrogenic aortic and mitral valve injuries. Moreover, we have summarized our recommendations emphasizing the need for careful management and meticulous follow-up of these patients to avoid such potentially devastating complications.

Utilization of extracorporeal membrane oxygenation in DCD and DBD lung transplants: a 2-year single-center experience.

Donation after circulatory death (DCD) has the potential to expand the lung donor pool. We aimed to assess whether DCD affected the need for perioperative extracorporeal membrane oxygenation (ECMO) and perioperative outcomes in lung transplantation (LTx) as compared to donation after brain death (DBD). All consecutive LTxs performed between April 2017 and March 2019 at our tertiary center were analyzed. Donor and recipient preoperative characteristics, utilization of ECMO, and perioperative clinical outcomes were compared between DCD and DBD LTx. Multivariate models (frequentist and Bayes) were fitted to evaluate an independent effect of DCD on the intra- and postoperative need for ECMO. Out of 105 enrolled patients, 25 (23.8%) were DCD LTx. Donors' and preoperative recipients' characteristics were comparable between the groups. Intraoperatively, mechanical circulatory support (MCS) was more common in DCD LTx (56.0% vs. 36.2%), but the adjusted difference was minor (RR = 1.16, 95% CI 0.64-2.12; P = 0.613). MCS duration, and first and second lung ischemia time were longer in the DCD group. Postoperatively, DCD recipients more commonly required ECMO (32.0% vs. 7.5%) and the difference remained considerable after adjustment for the pre- and intraoperative covariates: RR = 4.11 (95% CI 0.95-17.7), P = 0.058, Bayes RR = 4.15 (95% CrI 1.28-13.0). Sensitivity analyses (two DCD-DBD matching procedures) supported a higher risk of postoperative ECMO need in DCD patients. Incidence of delayed chest closure, postoperative chest drainage, and renal replacement therapy was higher in the DCD group. Early postoperative outcomes after DCD LTx appeared generally comparable to those after DBD LTx. DCD was associated with a higher need for postoperative ECMO which could influence clinical outcomes. However, as the DCD group had a significantly higher use of EVLP with more common ECMO preoperatively, this might have contributed to worse outcomes in the DCD group.

Marker-Independent In Situ Quantitative Assessment of Residual Cryoprotectants in Cardiac Tissues.

Cryomedium toxicity is a major safety concern when transplanting cryopreserved organs. Therefore, thorough removal of potentially toxic cryoprotective agents (CPAs) is required before transplantation. CPAs such as dimethyl-sulfoxide (DMSO), propylene glycol (PG), and formamide (FMD), routinely employed in ice-free cryopreservation (IFC), have advantages in long-term preservation of tissue structures compared with conventional cryopreservation employing lower CPA concentrations. This study evaluated the impact of potential residual CPAs on human cardiac valves. Raman microspectroscopy and Raman imaging were established as nondestructive marker-independent techniques for in situ quantitative assessment of CPA residues in IFC valve tissues. In detail, IFC valve leaflets and supernatants of the washing solutions were analyzed to determine the washing efficiency. A calibration model was developed according to the CPA's characteristic Raman signals to quantify DMSO, PG and FMD concentrations in the supernatants. Single point Raman measurements were performed on the intact tissues to analyze penetration properties. In addition, Raman imaging was utilized to visualize potential CPA residues. Our data showed that washing decreased the CPA concentration in the final washing solution by 99%, and no residues could be detected in the washed tissues, validating the multistep CPA removal protocol routinely used for IFC valves. Raman analysis of unwashed tissues showed different permeation characteristics depending on each CPA and their concentration. Our results demonstrate a great potential of Raman microspectroscopy and Raman imaging as marker-independent in situ tissue quality control tools with the ability to assess the presence and concentration of different chemical agents or drugs in preimplantation tissues.

Xeno-immunogenicity of ice-free cryopreserved porcine leaflets.

BACKGROUND: Undesirable processes of inflammation, calcification, or immune-mediated reactions are limiting factors in long-term survival of heart valves in patients. In this study, we target the modulatory effects of ice-free cryopreservation (IFC) of xenogeneic heart valve leaflet matrices, without decellularization, on the adaptive human immune responses in vitro. METHODS: We tested porcine leaflet matrices from fresh untreated, conventionally cryopreserved (CFC), and IFC pulmonary valves by culturing them with human blood mononuclear cells for 5 d in vitro. No other tissue treatment protocols to modify possible immune responses were used. Matrices alone or in addition with a low-dose second stimulus were analyzed for induction of proliferation and cytokine release by flow cytometry-based techniques. Evaluation of the α-Gal epitope expression was performed by immunohistochemistry with fluorochrome-labeled B4 isolectin. RESULTS: None of the tested leaflet treatment groups directly triggered the proliferation of immune cells. But when tested in combination with a second trigger by anti-CD3, IFC valves showed significantly reduced proliferation of T cells, especially effector memory T cells, in comparison with fresh or CFC tissue. Moreover, the cytokine levels for interferon-γ (IFNγ), tumor necrosis factor α, and interleukin-10 were reduced for the IFC-treated group being significantly different compared with the CFC group. However, no difference between treatment groups in the expression of the α-Gal antigen was observed. CONCLUSIONS: IFC of xenogeneic tissue might be an appropriate treatment method or processing step to prevent responses of the adaptive immune system.

Fetuin-A influences vascular cell growth and production of proinflammatory and angiogenic proteins by human perivascular fat cells.

AIMS/HYPOTHESIS: Fetuin-A (alpha2-Heremans-Schmid glycoprotein), a liver-derived circulating glycoprotein, contributes to lipid disorders, diabetes and cardiovascular diseases. In a previous study we found that perivascular fat cells (PVFCs) have a higher angiogenic potential than other fat cell types. The aim was to examine whether fetuin-A influences PVFC and vascular cell growth and the expression and secretion of proinflammatory and angiogenic proteins, and whether TLR4-independent pathways are involved. METHODS: Mono- and co-cultures of human PVFCs and endothelial cells were treated with fetuin-A and/or palmitate for 6-72 h. Proteins were quantified by ELISA and Luminex, mRNA expression by real-time PCR, and cell growth by BrDU-ELISA. Some PVFCs were preincubated with a nuclear factor κB NFκBp65 inhibitor, or the toll-like receptor 4 (TLR4) inhibitor CLI-095, or phosphoinositide 3-kinase (PI3K)/Akt inhibitors and/or stimulated with insulin. Intracellular forkhead box protein O1 (FoxO1), NFκBp65 and inhibitor of κB kinase ß (IKKß) localisation was visualised by immunostaining. RESULTS: PVFCs expressed and secreted IL-6, IL-8, plasminogen activator inhibitor 1 (PAI-1), basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF)-BB, monocyte chemotactic protein-1 (MCP-1), vascular endothelial growth factor (VEGF), placental growth factor (PLGF) and hepatocyte growth factor (HGF). Fetuin-A upregulated IL-6 and IL-8, and this was potentiated by palmitate and blocked by CLI-095. Immunostaining and electrophoretic mobility shift assay (EMSA) showed partial NFκBp65 activation. MCP-1 was upregulated and blocked by CLI-095, but not by palmitate. However, HGF was downregulated, which was slightly potentiated by palmitate. This effect persisted after TLR4 pathway blockade. Stimulation of insulin-PI3K-Akt signalling by insulin resulted in nuclear FoxO1 extrusion and HGF upregulation. Fetuin-A counteracted these insulin effects. CONCLUSIONS/INTERPRETATION: Fetuin-A and/or palmitate influence the expression of proinflammatory and angiogenic proteins only partially via TLR4 signalling. HGF downregulation seems to be mediated by interference with the insulin-dependent receptor tyrosine kinase pathway. Fetuin-A may also influence angiogenic and proinflammatory proteins involved in atherosclerosis.

Methylene blue modulates adhesion molecule expression on microvascular endothelial cells.

OBJECTIVE AND DESIGN: As methylene blue (MB) has been recently proposed to preserve blood pressure in case of vasoplegic syndrome and shock, an entity directly related to systemic inflammation, we aimed to elucidate the effect of MB on the expression of adhesion-molecules in endothelial-cells. MATERIALS AND TREATMENT: Human microvascular endothelial-cells (HuMEC-1) were treated with 10, 30 or 60 µM MB for 30 min and 2 h each. Additionally, the treated HuMEC-1 were co-cultured with either human peripheral blood mononuclear cells (PBMCs) or Jurkat cells (human T-lymphocytes) for 2 h. METHODS: HuMEC-1 were analyzed after MB treatment and after co-culture experiments for expression of different adhesion-molecules (ICAM-1, VCAM-1, L-selectin, E-selectin) via FACS measurement and western blot analysis. The supernatants of the experiments were analyzed with regard to the soluble forms of the adhesion molecules. RESULTS: We found that MB is able to modulate the expression of adhesion-molecules on EC. Administration of MB increases the expression of E-selectin and VCAM-1 depending on the dosage and time of exposure. ICAM-1 measurements provide evidence that different circulating blood cells can differently alter the adhesion-molecule expression on EC after MB exposure. CONCLUSION: Our results provide evidence regarding the immunomodulatory effect of MB upon endothelial-cells after inflammation.

Associated factors for non-ischemic serum myoglobin release after cardiac surgical procedures.

BACKGROUND: Myoglobin has become established as a serum marker of myocardial injury. However, myoglobin levels can increase exponentially without any correlation to postoperative clinical ischemia symptoms. In this retrospective study, we analyzed the associated factors for a non-ischemic myoglobin release. METHODS: We performed a data analysis from 532 consecutive cardiac surgery patients (2010 to 2011, 73% males; age 65 ± 11 years). Non-ischemic myoglobin elevation was defined as CK-MB <50 U/l and/or the absence of any ischemic clinical events (eg, myocardial infarction, mesenteric vascular occlusion). RESULTS: Using a multifactorial model, predictive elements and associated factors for non-ischemic myoglobin increase were male sex, ejection fraction < 30%, BMI > 30 and transfusions. Serum myoglobin was not significantly different in patients with high muscle mass. CONCLUSIONS: A non-ischemic serum myoglobin release is rare, but could be associated in subgroups of patients. Further investigations should focus on clinical targets, for example, concomitant medications for which our study was not powered.

[Patient blood management--The preoperative patient]. / Patient Blood Management--Der präoperative Patient.

Preoperative anaemia is an independent risk factor for an increase in perioperative morbidity and mortality. Patient Blood Management (PBM) aims for an early detection of anaemia in elective surgery patients. Reasons for anaemia should be detected and causally treated if possible. A multidisciplinary team of specialists aims for diagnosis and causative treatment of easily treatable and frequent causes of anaemia like iron deficiency, bleeding or (autoimmune) haemolysis using patients' specific history, examination, laboratory and technical methods. Such an outpatient PBM programme is only feasible, if anaesthesiologists, surgeons, haematologists, gastroenterologists, gynecologists, laboratory and transfusion medicine specialists work together in a PBM team using a common PBM plan. Communication within this team as well as with the patients' physicians in their private offices is key for a long lasting success of such a PBM programme.

Association of Renin-Angiotensin-Aldosterone System Inhibitors With Clinical Outcomes, Hemodynamics, and Myocardial Remodeling Among Patients With Advanced Heart Failure on Left Ventricular Assist Device Support.

BACKGROUND: We evaluated the potential benefits of renin-angiotensin-aldosterone system inhibitors (RAASi) in patients with left ventricular assist device support. METHODS AND RESULTS: A total of 165 consecutive patients undergoing left ventricular assist device implant and alive at 6-month on support were studied. RAASi status after 6-month visit along with clinical reasons for nonprescription/uptitration were retrospectively assessed. The primary outcome was a composite of heart failure hospitalization or cardiovascular death between 6 and 24 months after left ventricular assist device implant. Remodeling and hemodynamic outcomes were explored by studying the association of RAASi new prescription/uptitration versus unmodified therapy at 6-month visit with the change in echocardiographic parameters and hemodynamics between 6 and 18 months. After the 6-month visit, 76% of patients were on RAASi. Patients' characteristics among those receiving and not receiving RAASi were mostly similar. Of 85 (52%) patients without RAASi new prescription/uptitration at 6-month visit, 62% had no apparent clinical reason. RAASi were independently associated with the primary outcome (adjusted hazard ratio, 0.31 [95% CI, 0.16-0.69]). The baseline rates of optimal echocardiographic profile (neutral interventricular septum, mitral regurgitation less than mild, and aortic valve opening) and hemodynamic profile (cardiac index ≥2.2 L/min per m2, wedge pressure <18 mm Hg, and right atrial pressure <12 mm Hg) were similar between groups. At 18 months, patients receiving RAASi new prescription/uptitration at 6 months had higher rates of optimal hemodynamic profile (57.5% versus 37.0%; P=0.032) and trends for higher rates of optimal echocardiographic profile (39.6% versus 22.9%; P=0.055) compared with patients with 6-month unmodified therapy. Optimal 18-month hemodynamic and echocardiographic profiles were associated with the primary outcome (log-rank=0.022 and log-rank=0.035, respectively). CONCLUSIONS: RAASi are associated with improved outcomes and improved hemodynamics among mechanically unloaded patients.

Bridge to recovery or permanent system implantation: an eight-year single-center experience in transvenous semipermanent pacing.

BACKGROUND: To compare the risks, implications, and outcomes of transvenous semipermanent pacing as a bridge to permanent system implantation or recovery. METHODS: We investigated semipermanent transvenous pacing systems consisting of one (n = 57%) or two (n = 3%) bipolar active-fixation pacing leads and an attached epicutaneous pulse generator implanted from 2000 to 2009. The study population comprised 60 patients aged 72.9 ± 10.5 years (44 [73.3%] male). Forty-two (70%) were enrolled for complete system explantation for cardiac-implanted electronic devices associated infection. Eighteen (30%) required temporary pacing in the context of a variety of mostly severe cardiac and noncardiac conditions. The semipermanent pacing systems were removed after implantation of permanent systems or recovery of a noncompromising heart rhythm, respectively. RESULTS: Transvenous semipermanent lead implantation was successful in 59 (98.3%) patients. Major and minor intraoperative complications occurred in one case (1.7%) each. The semipermanent systems were left in situ for a mean period of 14.6 ± 8.1 days). They served as a bridge to permanent system implantation in 68.3% (n = 41) and as a bridge to recovery of a noncompromising heart rhythm in 11.7% (n = 7). Four patients (8.3%) died with the semipermanent pacing system in situ, and seven (11.7%) were transferred to external hospitals with semipermanent pacing systems. CONCLUSIONS: Transvenous semipermanent pacing with bipolar active-fixation leads and epicutaneous pulse generators provide an important option for prolonged temporary pacing as a bridge to permanent system implantation or recovery.

Fibrin sealant patch for repair of acute type a aortic dissection.

INTRODUCTION: The use of glues to repair disrupted tissue during acute type-A aortic dissection (TAD) surgery may be discontinuous, and cause embolization and cell necrosis. We report a method of fibrin sealant patch (FSP) to reinforce dissected aortic tissue with a collagen double layer coated with fibrinogen/thrombin on either side (TachoSil®; Takeda, Konstanz, Germany). METHODS: In 12 patients (seven male, 66.9 ± 11.7 years) with acute TAD we performed FSP of the intima-media disruption at the proximal and distal anastomosis of the aorta. We analyzed the perioperative course and echocardiographical, radiological, and clinical outcomes up to one year. Additionally, we investigated the adhesive potential of the FSP in vitro. RESULTS: In vitro, the adhesive strength of the FSP was 60 N/cm(2). In-hospital mortality was 8.3% (n = 1), recovery was satisfactory with no major neurologic events, mean ICU stay was 13.6 ± 6.0 days, mean hospital stay was 20.7 ± 4.4 days. A total of 7.0 ± 2.6 RBC, 3.4 ± 1.5 platelets, and 8.0 ± 4.3 FFP were transfused. One-year survival was 83.3%. In 6/6 DeBakey II dissections the intimal tear was completely resected, in 2/6 DeBakey I dissections the false lumen in the descending aorta completely collapsed. No redissections and no relevant aortic valve insufficiencies were seen during follow-up. CONCLUSION: This analysis shows that FSP using a collagen matrix double layer coated with fibrinogen/thrombin is feasible, safe, and effective in repairing the dissected aortic tissue. It results in continuous reinforcement of aortic tissue and completely avoids the need for conventional glues.

How to test adhesive strength: a biomechanical testing for aortic glue used in type a dissection repair.

OBJECTIVES: The aim of this study was to develop a method to quantify the peel force in an in vitro model simulating repair of ascending aortic dissections with tissue glue (Bioglue). METHODS: This study adapted an adhesive T-Peel test for the determination of the peel strength of adhesives by measuring the peeling force of a T-shaped bonded tissue. Measurements were performed on iatrogenic dissected ascending porcine aorta, which has been repaired with Bioglue using different pressure levels. Four conditions were tested: zero sample pressure according to the manufacturer's recommendation (n = 10), low (504 Pa; n = 11), moderate pressure (1711 Pa; n = 24) and pressure applied by a round shaped vascular 'Borst clamp' (1764 Pa; n = 23). Non-parametric one-way analysis of variance was applied for statistical significance. RESULTS: The median peel force (lower quartile, upper quartile) of aortic samples increased depending on the applied pressure: [no pressure 0.030 N/mm (0.016, 0.057), low pressure 0.040 N/mm (0.032, 0.070) and moderate pressure 0.214 N/mm (0.050, 0.304)]. Samples pressurized with the Borst clamp reached 0.078 N/mm (0.046, 0.152), which was comparable to the peel force of the unpeeled controls [0.107 N/mm (0.087, 0.124)]. Compared to samples without pressure, Bioglue with the application of the Borst clamp (P = 0.021) and with moderate pressure (P = 0.0007) performed significantly better. CONCLUSIONS: The novel T-Peel test offers an attractive method to test tissue glues in defined in vitro environments. Bioglue peel force increased with pressure on the aortic sample in contrast to low or no pressure as per the manufacturer's recommendation. Modifying current recommended use may aid in increasing effectiveness of this approach.

Risk of prolonged ischemic time linked to use of cardiopulmonary bypass during implantation for lung transplantation in the United Kingdom.

BACKGROUND: Some degree of ischemia is inevitable in organ transplantation, and for most, if not all organs, there is a relationship between ischemic time and transplant outcome. The contribution of ischemic time to lung injury is unclear, with conflicting recent data. In this study, we investigate the impact of ischemia time on survival after lung transplantation in a large national cohort. METHODS: We studied the outcomes for 1,565 UK adult lung transplants over a 12-year period, for whom donor, transplant, and recipient data were available from the UK Transplant Registry. We examined the effect of ischemia time (defined as donor cross-clamp to recipient reperfusion) and whether standard cardiopulmonary bypass was used using Cox proportional hazards models, adjusting for other risk factors. RESULTS: The total ischemic time increased from a median under 5 hours in 2003 to over 6.2 hours in 2013. Our findings show that, when the cardiopulmonary bypass was used, there was an increase in the hazard of death (of 13% [95% CI: 5%-21%] for 1-year patient survival) for each hour of total ischemic time. However, if the cardiopulmonary bypass was not used for implantation, this link disappeared-there was no statistically significant change in mortality with increasing ischemic time. CONCLUSIONS: We document that avoidance of bypass may remove ischemic time, within the limits of our observed range of ischemic times, as a risk factor for poor outcomes. Our data add to the evidence that bypass may be harmful to the donor lung.