Porcine lungs perfused with three different flows using the 8-h open-atrium cellular ex vivo lung perfusion technique.

The number of lung transplantations is limited due to the shortage of donor lungs fulfilling the standard criteria. The ex vivo lung perfusion (EVLP) technique provides the ability of re-evaluating and potentially improving and treating marginal donor lungs. Accordingly, the technique has emerged as an essential tool to increase the much-needed donor lung pool. One of the major EVLP protocols, the Lund protocol, characterized by high pulmonary artery flow (100% of cardiac output [CO]), an open atrium, and a cellular perfusate, has demonstrated encouraging short-EVLP duration results. However, the potential of the longer EVLP duration of the protocol is yet to be investigated, a duration which is considered necessary to rescue more marginal donor lungs in future. This study aimed to achieve stable 8-h EVLP using an open-atrium cellular model with three different pulmonary artery flows in addition to determining the most optimal flow in terms of best lung performance, including lung electrolytes and least lung edema formation, perfusate and tissue inflammation, and histopathological changes, using the porcine model. EVLP was performed using a flow of either 40% (n = 6), 80% (n = 6), or 100% (n = 6) of CO. No flow rate demonstrated stable 8-h EVLP. Stable 2-h EVLP was observed in all three groups. Insignificant deterioration was observed in dynamic compliance, peak airway pressure, and oxygenation between the groups. Pulmonary vascular resistance increased significantly in the 40% group (p < .05). Electrolytes demonstrated an insignificant worsening trend with longer EVLP. Interleukin-8 (IL-8) in perfusate and tissue, wet-to-dry weight ratio, and histopathological changes after EVLP were insignificantly time dependent between the groups. This study demonstrated that stable 8-h EVLP was not feasible in an open-atrium cellular model regardless of the flow of 40%, 80%, or 100% of CO. No flow was superior in terms of lung performance, lung electrolytes changes, least lung edema formation, minimal IL-8 expression in perfusate and tissue, and histopathological changes.

Long-term outcomes of lung transplantation with ex vivo lung perfusion technique.

Ex vivo lung perfusion (EVLP) has demonstrated encouraging short- and medium-term outcomes with limited data available on its long-term outcomes. This study assesses (1) EVLP long-term outcomes and (2) EVLP era-based sub-analysis in addition to secondary outcomes of recipients with EVLP-treated donor lungs compared with recipients of conventionally preserved donor lungs in unmatched and propensity score-matched cohorts. Double lung transplants performed between 1st January 2012 and 31st December 2021 were included. A total of 57 recipients received EVLP-treated lungs compared to 202 unmatched and 57 matched recipients who were subjected to non-EVLP-treated lungs. The EVLP group had a significantly lower mean PaO2/FiO2 ratio and significantly higher mean BMI than the non-EVLP group in the unmatched and matched cohorts. The proportion of smoking history in the unmatched cohort was significantly higher in the EVLP group, while a similar smoking history was demonstrated in the matched cohorts. No difference was demonstrated in overall freedom from death and retransplantation between the groups in the unmatched and matched cohorts (unmatched: hazard ratio (HR) 1.28, 95% confidence interval (CI) 0.79-2.07, P = 0.32; matched: HR 1.06, 95% CI 0.59-1.89). P = 0.89). In the unmatched cohort, overall freedom from chronic allograft dysfunction (CLAD) was significantly different between the groups (HR 1.64, 95% CI 1.07-2.52, P = 0.02); however, the cumulative CLAD incidence was similar (HR 0.72, 95% CI 0.48-1.1, P = 0.13). In the matched cohort, the overall freedom from CLAD (HR 1.69, 95% CI 0.97-2.95, P = 0.06) and cumulative CLAD incidence (HR 0.91, 95% CI 0.37-2.215, P = 0.83) were similar between the groups. The EVLP era sub-analysis of the unmatched cohort in 2012-2014 had a significantly higher cumulative CLAD incidence in the EVLP group; however, this was not demonstrated in the matched cohort. All secondary outcomes were similar between the groups in the unmatched and matched cohorts. In conclusion, transplantation of marginal donor lungs after EVLP evaluation is non-detrimental compared to conventionally preserved donor lungs in terms of mortality, retransplantation, cumulative CLAD incidence, and secondary outcomes. Although the unmatched EVLP era of 2012-2014 had a significantly higher cumulative CLAD incidence, no such finding was demonstrated in the matched cohort of the same era.

Changes in aortic valve replacement procedures in Denmark from 2008 to 2020.

INTRODUCTION: Since 2007, transcatheter aortic valve implantation (TAVI) has emerged as another treatment strategy for severe symptomatic aortic stenosis (AS) compared with surgical aortic valve replacement (SAVR). The objectives were to compare annual rates of aortic valve replacement (AVR) procedures performed in Denmark in the era of TAVI and to assess proportion of AVRs stratified by age with use of age recommendations presented in current guidelines. METHODS: Using Danish nationwide registries, we identified first-time AVRs between 2008 and 2020. Patients who were not diagnosed with AS prior to AVR were excluded RESULTS: The rate of AVRs increased by 39% per million inhabitants from 2008 to 2020. TAVI has steadily increased since 2008, accounting for 64.2% of all AVRs and 72.5% of isolated AVRs by 2020. Number of isolated SAVRs decreased from 2014 and onwards. The proportion of TAVI increased significantly across age groups (<75 and ≥75 years of age, ptrend<0.001), and TAVI accounted for 91.5% of isolated AVR procedures in elderly patients (aged ≥75 years). Length of hospital stay were significantly reduced for all AVRs during the study period (ptrend all<0.001). CONCLUSIONS: The number of AVRs increased from 2008 to 2020 due to adaptation of TAVI, which represented 2/3 of AVRs and more than 70% of isolated AVRs. In elderly patients, the increased use of AVR procedures was driven by TAVI, in agreement with the age recommendations in current guidelines; however, TAVI was used more frequently in patients aged <75 years, accompanied by a flattening use of SAVR.

Dual or single antiplatelet therapy after coronary surgery for acute coronary syndrome (TACSI trial): Rationale and design of an investigator-initiated, prospective, multinational, registry-based randomized clinical trial.

The TACSI trial (ClinicalTrials.gov Identifier: NCT03560310) tests the hypothesis that 1-year treatment with dual antiplatelet therapy with acetylsalicylic acid (ASA) and ticagrelor is superior to only ASA after isolated coronary artery bypass grafting (CABG) in patients with acute coronary syndrome. The TACSI trial is an investigator-initiated pragmatic, prospective, multinational, multicenter, open-label, registry-based randomized trial with 1:1 randomization to dual antiplatelet therapy with ASA and ticagrelor or ASA only, in patients undergoing first isolated CABG, with a planned enrollment of 2200 patients at Nordic cardiac surgery centers. The primary efficacy end point is a composite of time to all-cause death, myocardial infarction, stroke, or new coronary revascularization within 12 months after randomization. The primary safety end point is time to hospitalization due to major bleeding. Secondary efficacy end points include time to the individual components of the primary end point, cardiovascular death, and rehospitalization due to cardiovascular causes. High-quality health care registries are used to assess primary and secondary end points. The patients will be followed for 10 years. The TACSI trial will give important information useful for guiding the antiplatelet strategy in acute coronary syndrome patients treated with CABG.

Glucagon-like peptide-1 stimulates acute secretion of pro-atrial natriuretic peptide from the isolated, perfused pig lung exposed to warm ischemia.

Glucagon-like peptide-1 (GLP-1) has proven to be protective in animal models of lung disease but the underlying mechanisms are unclear. Atrial natriuretic peptide (ANP) is mainly produced in the heart. As ANP possesses potent vaso- and bronchodilatory effects in pulmonary disease, we hypothesised that the protective functions of GLP-1 could involve potentiation of local ANP secretion from the lung. We examined whether the GLP-1 receptor agonist liraglutide was able to improve oxygenation in lungs exposed to 2 h of warm ischemia and if liraglutide stimulated ANP secretion from the lungs in the porcine ex vivo lung perfusion (EVLP) model. Pigs were given a bolus of 40 µg/kg liraglutide or saline 1 h prior to sacrifice. The lungs were then left in vivo for 2 h, removed en bloc and placed in the EVLP machinery. Lungs from the liraglutide treated group were further exposed to liraglutide in the perfusion buffer (1.125 mg). Main endpoints were oxygenation capacity, and plasma and perfusate concentrations of proANP and inflammatory markers. Lung oxygenation capacity, plasma concentrations of proANP or concentrations of inflammatory markers were not different between groups. ProANP secretion from the isolated perfused lungs were markedly higher in the liraglutide treated group (area under curve for the first 30 min in the liraglutide group: 635 ± 237 vs. 38 ± 38 pmol/L x min in the saline group) (p < 0.05). From these results, we concluded that liraglutide potentiated local ANP secretion from the lungs.

Comprehensive assessment of frailty score supplements the existing cardiac surgical risk scores.

OBJECTIVES: The commonly used cardiac surgery risk scores, European System for Cardiac Operative Risk Evaluation II and Society of Thoracic Surgeons score, are inaccurate in predicting mortality in the ageing patient population and do not include the biological age. This requests a need for a new risk score incorporating frailty. The aim of this study was to compare the prediction of mortality and the additive effect of comprehensive assessment of frailty score and the shortened version, frailty predicts death one year after elective cardiac surgery test on the existing risk scores. METHODS: Six hundred four patients undergoing cardiac surgery and aged ≥65 years were included in this prospective observational study. These frailty scores are based on minor physical tests. We compared these frailty score predictions of mortality and their added value to the existing risk scores evaluated by concordance-statistics (C-statistics), integrated discrimination improvement and net reclassification improvement. RESULTS: The median age was 73 years (21% female). C-statistics showed that comprehensive assessment of frailty score with a value of 0.69, frailty predicts death one year after elective cardiac surgery test 0.68, Society of Thoracic Surgeons score 0.70 and European System for Cardiac Operative Risk Evaluation 0.64. Frailty assessment, added to the existing risk scores, significantly improved integrated discrimination improvement up to 0.05, and net reclassification improvement up to 0.04. Frailty assessment also increased the C-statistics, but this did not reach statistical significance. CONCLUSIONS: Frailty scores are as good as the existing risk scores for the prediction of mortality in patients undergoing cardiac surgery. Added to the existing scores, frailty assessment improves the C-statistics and integrated discrimination improvement over time. CLINICAL TRIALS REGISTRATION NUMBER: NCT02992587.

One-year mortality increases four-fold in frail patients undergoing cardiac surgery.

OBJECTIVES: An increased focus on biological age, 'frailty', is important in an ageing population including those undergoing cardiac surgery. None of the existing surgery risk scores European System for Cardiac Operative Risk Evaluation II or Society of Thoracic Surgeons score incorporates frailty. Therefore, there is a need for an additional risk score model including frailty and not simply the chronological age. The aim of this study was to evaluate the impact of frailty assessment on 1-year mortality and morbidity for patients undergoing cardiac surgery. METHODS: A total of 604 patients aged ≥65 years undergoing non-acute cardiac surgery were included in this single-centre prospective observational study. We compared 1-year mortality and morbidity in frail versus non-frail patients. The Comprehensive Assessment of Frailty (CAF) score was used: This is a score of 1-35 determined via minor physical tests. A CAF score ≥11 indicates frailty. RESULTS: The median age was 73 years and 79% were men. Twenty-five percent were deemed frail. Frail patients had four-fold, odds ratios 4.63, 95% confidence interval (CI) 2.21-9.69; P < 0.001 increased 1-year mortality and increased risk of postoperative complications, i.e. surgical wound infections and prolonged hospital length of stay. A univariable Cox proportional hazards regression showed that an increased CAF score was a risk factor of mortality at any time after undergoing cardiac surgery (hazards ratios 1.11, 95% CI 1.07-1.14; P < 0.001). CONCLUSIONS: CAF score identified frail patients undergoing cardiac surgery and was a good predictor of 1-year mortality. CLINICAL TRIAL REGISTRATION NUMBER: NCT02992587.

Felodipine and renal function in lung transplantation: A randomized placebo-controlled trial.

BACKGROUND: Calcium channel blockers may ameliorate the decline in renal function caused by calcineurin inhibitors in lung transplantation (LTX) recipients. We hypothesized that pre-operative and 12-week post-operative treatment with the calcium channel blocker felodipine would reduce the decline in glomerular filtration rate (GFR). METHODS: In this prospective, randomized, double-blind trial, 39 LTX recipients were transplanted and received placebo (n = 19; GFR, 102 ml/min/1.73 m2 [range, 91-113 ml/min/1.73 m2]) or felodipine (n = 20, GFR, 96 ml/min/1.73 m2 [range, 88-104 ml/min/1.73 m2]). Pre-operative treatment was titrated post-operatively to 10 mg or the maximum tolerable dose. The primary end-point was the change in GFR using Cr-51-labeled EDTA from LTX to 12 weeks thereafter, and follow-up was 52 weeks. RESULTS: The treatment group showed an absolute mean decline in GFR of 31 ml/min/1.73 m2 (95% CI: -40 to 22 ml/min/1.73 m2), whereas that of the placebo group was 48 ml/min/1.73 m2 (95% confidence interval [CI]: -56 to 40 ml/min/1.73 m2). Thus, the difference between groups at 12 weeks was 17 ml/min/1.73 m2 (95% CI: 4-29 ml/min/1.73 m2; p = 0.01). Half of the patients were unable to complete the 3-month primary follow-up, and the analysis includes these patients by intention-to-treat. After 52 weeks (40 weeks after termination of treatment), the treatment effect was maintained at 12 ml/min/1.73 m2 (95% CI: 0-24 ml/min/1.73 m2, p = 0.05). The number of days with registered hypotension was significantly higher in the felodipine group than in the placebo group (39 days vs 13 days, rate ratio: 2.9 [95% CI: 1.5-5.3]). CONCLUSIONS: Use of felodipine in select patients was associated with greater preservation in renal function early (90 days) after LTX. The observed benefits were attenuated by 1 year, although trends in better renal function were noted.

30-day mortality in frail patients undergoing cardiac surgery: the results of the frailty in cardiac surgery (FICS) copenhagen study.

Objectives. Typically, patients referred to cardiac surgery are aged. Because EuroSCORE tend to overestimate and STS tend to underestimate the risk of mortality after cardiac surgery, frailty has become interesting as a potential predictor for mortality after cardiac surgery. Therefore, we conducted a study to identify the number of frail patients undergoing cardiac surgery and describe the risk of short-term complications and mortality. Design. In a prospective observational study, we have compared the surgical outcome in frail versus non-frail patients. Patients aged > 65 years and undergoing non-acute cardiac surgery were included. Frailty was assessed using the comprehensive assessment of frailty (CAF) score. The CAF evaluates the patient's physical condition through performing physical tests. Results. 604 patients included, 477 were men and the median age was 73 years (range, 65-90). Twenty-five percent were deemed frail. Frail patients had a four times higher 30-day mortality. Furthermore, frail patients had higher postoperative complication rates of atrial fibrillation, prolonged ventilation, re-operations, renal failure, transfusion requirements, and increased length of stay. Patients who died within 30 days had a significantly higher CAF score than those who survived (p = .039). Based on ROC curves, the area under the curve (AUC) for CAF score was 0.700, EuroSCORE 0.664 and STS score 0.748. Conclusion. Frailty is common in patients undergoing cardiac surgery and carries increased risk of 30-day mortality and postoperative complications. The AUC indicates similar prediction of mortality for CAF score compared to the existing risk scores. Clinical Trials Registration ID: NCT02992587.

Higher arterial pressure during cardiopulmonary bypass may not reduce the risk of acute kidney injury.

BACKGROUND: Acute kidney injury after cardiac surgery is common and associated with increased mortality. It is unknown whether an intended higher arterial pressure during cardiopulmonary bypass reduces the incidence of acute and chronic kidney injury. METHODS: Patients were randomised either to a control group or a high pressure group (arterial pressure > 60 mmHg). The inclusion criteria were age > 70 years, combined cardiac surgery and serum creatinine < 200 µmol/L. Glomerular filtration rate using the Cr-EDTA clearance method was measured the day before surgery and 4 months postoperatively. The RIFLE criteria were used to define the presence of acute kidney injury. In addition, the ratio between urinary Neutrophil Gelatinase-Associated Lipocalin (NGAL) and creatinine was measured. RESULTS: Ninety patients were included. Mean age was 76 ± 4 years and 76% were male. Mean arterial pressure was 47 ± 5 mmHg in the control group and 61 ± 4 mmHg in the high pressure group (p < 0.0001). The change in glomerular filtration rate at follow-up was - 9 ± 12 ml/min in the control group and - 5 ± 16 ml/min in the high pressure group (p = 0.288, 95% CI - 13 to 4). According to the RIFLE criteria 38% in the control group and 46% in the high pressure group developed acute kidney injury (p = 0.447). The postoperative urinary NGAL/creatinine ratio was comparable between the groups. CONCLUSIONS: An intended increase in arterial pressure during cardiopulmonary bypass to > 60 mmHg did not decrease the incidence of acute or chronic kidney injury after cardiac surgery. TRIAL REGISTRATION: Clinicaltrials.gov, identifier: NCT01408420 . Registered 3rd of August 2011.

Chronic pain after bilateral thoracotomy in lung transplant patients.

Background and aims The relative contribution of patient-related factors and intraoperative nerve damage for the development of chronic pain after surgery is unclear. This study aimed to examine chronic pain after bilateral thoracotomy. We hypothesized, that individual patient-related risk factors would be important resulting in an intraindividual uniformity of pain and hyperphenomena between the two sides of the thorax. Methods Twenty patients who had undergone lung transplantation via bilateral thoracotomy 6-12 months previously were included from the Danish Lung Transplant program, Rigshospitalet, Denmark, from October 2016 to August 2017. All patients answered questionnaires about pain in and around the scar, completed the Neuropathic Pain Symptom Inventory, and underwent bedside examination for hyperphenomena (brush- and cold-evoked allodynia, pinprick hyperalgesia) and pinprick hypoalgesia. Results Nine patients reported spontaneous pain bilaterally, five patients had pain on one side only, and six patients had no pain. Hyperphenomena were present on both sides of the thorax in 13 patients, on one side in four patients, and three patients had no hyperphenomena. The intraindividual uniformity of pain (p=0.029) and hyperphenomena (p=0.011) between the two sides of the thorax suggests that patient-related factors play an important role in the development of chronic pain. Conclusions The results of the present study provide support for the hypothesis of an individual predisposition for the development of chronic pain after thoracotomy. Implications Patient-related risk factors contribute to the development of chronic pain after thoracotomy. This result most likely can be transferred to chronic pain after other surgical procedures and therefore help us understand risk factors for chronic pain after surgery.

Surgical embolectomy compared to thrombolysis in acute pulmonary embolism: morbidity and mortality.

OBJECTIVES: The aim of this study was to investigate the long-term outcome after acute high- and intermediate-risk pulmonary embolism (PE) treated with surgical embolectomy or thrombolysis. METHODS: Prospective follow-up including assessment of 30-day and 5-year mortality. Clinical evaluation including ventilation/perfusion scintigraphy by single-photon emission computed tomography in combination with X-ray computed tomography, measurement of pulmonary diffusion impairment, spirometry and echocardiography. RESULTS: A total of 136 patients (64 with high-risk and 72 with intermediate-risk PE) were included, 80 participated in the clinical follow-up, 16 were alive but declined follow-up and 40 were deceased. For high-risk PE patients the median time to clinical follow-up was 31 months [8­133]. No significant difference was observed in 30-day (Plog-rank = 0.16) or 5-year (Plog-rank = 0.53) mortality between patients treated with surgical embolectomy or thrombolysis. Ventilation/perfusion mismatch identified residual emboli in 4 patients (31%) treated with surgical embolectomy compared to 16 (76%) treated with thrombolysis (P = 0.009). Pulmonary diffusion impairment was identified in 4 patients (31%) treated with surgical embolectomy in comparison to 15 (71%) treated with thrombolysis (P = 0.02). In intermediate-risk PE patients, no significant difference in mortality (Plog-rank = 0.51 and 0.86), diffusion impairment or ventilation/perfusion mismatch was found between patients treated with surgical embolectomy or thrombolysis. CONCLUSIONS: Surgical embolectomy for acute high-risk PE has similar mortality, but better outcome on pulmonary end-points when compared to thrombolysis. Patients with high-risk PE could benefit from being referred to a centre with both specialized cardiology and cardiothoracic surgery for interdisciplinary evaluation of optimal treatment strategy.

Coagulopathy in patients with acute pulmonary embolism: a pilot study of whole blood coagulation and markers of endothelial damage.

Whole blood coagulation and markers of endothelial damage were studied in patients with acute pulmonary embolism (PE), and evaluated in relation to PE severity. Twenty-five patients were enrolled prospectively each having viscoelastical analysis of whole blood done using thrombelastography (TEG) and Multiplate aggregometry. Fourteen of these patients were investigated for endothelial damage by ELISA measurements of Syndecan-1 (endothelial glycocalyx degradation), soluble endothelial Selectin (endothelial cell activation), soluble Thrombomodulin (endothelial cell injury) and Histone Complexed DNA fragments (endothelial cytotoxic histones). The mean values of TEG and Multiplate parameters were all within the reference levels, but a significant difference between patients with high and intermediate risk PE was observed for Ly30 (lytic activity) 1.5% [0-10] vs. 0.2% [0-2.2] p = .04, and ADP (platelet reactivity) 92 U [20-145] vs. 59 U [20-111] p = .03. A similar difference was indicated for functional fibrinogen 21 mm [17-29] vs. 18 mm [3-23] p = .05. Analysis of endothelial markers identified a significant difference in circulating levels between high and intermediate risk PE patients for Syndecan-1 118.6 ng/mL [76-133] vs. 36.3 ng/mL [11.8-102.9] p = .008. In conclusion, patients with acute PE had normal whole blood coagulation, but high risk PE patients had signs of increased activity of the haemostatic system and significantly increased level of endothelial glycocalyx degradation.

Transit-time flow measurement as a predictor of coronary bypass graft failure at one year angiographic follow-up.

BACKGROUND: Transit-time flow measurement (TTFM) is a commonly used intraoperative method for evaluation of coronary artery bypass graft (CABG) anastomoses. This study was undertaken to determine whether TTFM can also be used to predict graft patency at one year postsurgery. METHODS: Three hundred forty-five CABG patients with intraoperative graft flow measurements and one year angiographic follow-up were analyzed. Graft failure was defined as more than 50% stenosis including the "string sign." Logistic regression analysis was used to analyze the risk of graft failure after one year based on graft vessel type, anastomatic configuration, and coronary artery size. RESULTS: Nine hundred eighty-two coronary anastomoses were performed of which 12% had signs of graft failure at one year angiographic follow-up. In internal mammary arteries (IMAs), analysis showed a 4% decrease in graft failure odds for every 1 mL/min increase in TTFM (OR = 0.96, CI = [0.93; 0.99], p = 0.005). ROC analysis showed good discriminative ability for TTFM alone AUC = 69.5% in IMA grafts. For single-vein grafts the decrease in graft failure odds was 2% for every 1 mL/min increase in TTFM (OR = 0.98; CI = [0.97; 1.00], p = 0.059) and AUC of 59.9%. There were no significant relationships between TTFM and graft failure in other graft types or graft configurations. CONCLUSION: The TTFM method has good discriminative ability for assessing the risk of graft failure in certain graft types within the first year after CABG surgery and is a valuable instrument for intraoperative quality assessment of bypass grafts.

Acute kidney injury is independently associated with higher mortality after cardiac surgery.

OBJECTIVES: To investigate the incidence of acute kidney injury after cardiac surgery and its association with mortality in a patient population receiving ibuprofen and gentamicin perioperatively. DESIGN: Retrospective study with Cox regression analysis to control for possible preoperative, intraoperative and postoperative confounders. SETTING: University hospital-based single-center study. PARTICIPANTS: All patients who underwent coronary artery bypass grafting ± valve surgery during 2012. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Acute surgery within 24 hours of coronary angiography, previous nephrectomy, preoperative sCr >2.26 mg/dL and selective cerebral perfusion during cardiopulmonary bypass were used as exclusion criteria. Acute kidney injury was defined, using the Acute Kidney Injury Network (AKIN) criteria. Six hundred eight patients were included in the study. Mean age was 68.2 ± 9.7 years, and 81% were males. Acute kidney injury was seen in 28.1% of the patients. Overall mortality at one year was 7% and 3% in the no-AKI group. At one year, mortality was 15% in patients with AKIN stage 1 and AKIN stage 2 compared to 70% in AKIN stage 3. A hazard ratio of 2.34 (95% CI: 1.21-4.51, p = 0.011) and 5.62 (95% CI: 2.42-13.06), p<0.0001) were found for AKIN stage 1 and 2/3 combined, respectively. CONCLUSIONS: More than 28% of the patients undergoing elective or subacute cardiac surgery developed AKI in this contemporary cohort. Furthermore, acute kidney injury was an independent predictor of increased mortality irrespective of the perioperative risk factors.

Conditioning techniques and ischemic reperfusion injury in relation to on-pump cardiac surgery.

OBJECTIVES: The objective was to investigate the potential protective effects of two conditioning methods, on myocardial ischemic and reperfusion injury in relation to cardiac surgery. DESIGN: Totally 68 patients were randomly assigned to either a control group (n = 23), a remote ischemic preconditioning (RIPC) group (n = 23) or a glucagon-like peptide-1 (GLP-1) analogue group (n = 22). The RIPC protocol consisted of three cycles of upper limb ischemia. The GLP-1 analogue protocol consisted of intravenous infusion with exenatide. The primary endpoint was postoperative cardiac enzyme release. The other secondary endpoints were metabolic parameters related to myocardial ischemia, measured using microdialysis technique, as well as other operative- and postoperative data. RESULTS: Postoperative cardiac enzyme release indicated a possible beneficial effect of the interventions, but the difference did not reach statistical significance. RIPC showed a trend toward lower levels (p = 0.07). We managed to establish a functional myocardial microdialysis model, but we were unable to demonstrate clear protective effects. CONCLUSIONS: We were in this prospective randomized proof-of-concept trial, unable to show distinct protective effects of the studied conditioning methods. However, this trial can hopefully contribute to generate a productive discussion concerning limitations and future use of cardiac conditioning as well as microdialysis technique.

Off-pump versus on-pump coronary artery bypass grafting.

Coronary artery bypass grafting (CABG) remains the preferred treatment in patients with complex coronary artery disease. However, whether the procedure should be performed with or without the use of cardiopulmonary bypass, referred to as off-pump and on-pump CABG, is still up for debate. Intuitively, avoidance of cardiopulmonary bypass seems beneficial as the systemic inflammatory response from extracorporeal circulation is omitted, but no single randomized trial has been able to prove off-pump CABG superior to on-pump CABG as regards the hard outcomes death, stroke or myocardial infarction. In contrast, off-pump CABG is technically more challenging and may be associated with increased risk of incomplete revascularization. The purpose of the review is to summarize the current literature comparing outcomes of off-pump versus on-pump coronary artery bypass surgery.

Immunosuppressive T-cell antibody induction for heart transplant recipients.

BACKGROUND: Heart transplantation has become a valuable and well-accepted treatment option for end-stage heart failure. Rejection of the transplanted heart by the recipient's body is a risk to the success of the procedure, and life-long immunosuppression is necessary to avoid this. Clear evidence is required to identify the best, safest and most effective immunosuppressive treatment strategy for heart transplant recipients. To date, there is no consensus on the use of immunosuppressive antibodies against T-cells for induction after heart transplantation. OBJECTIVES: To review the benefits, harms, feasibility and tolerability of immunosuppressive T-cell antibody induction versus placebo, or no antibody induction, or another kind of antibody induction for heart transplant recipients. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 11, 2012), MEDLINE (Ovid) (1946 to November Week 1 2012), EMBASE (Ovid) (1946 to 2012 Week 45), ISI Web of Science (14 November 2012); we also searched two clinical trial registers and checked reference lists in November 2012. SELECTION CRITERIA: We included all randomised clinical trials (RCTs) assessing immunosuppressive T-cell antibody induction for heart transplant recipients. Within individual trials, we required all participants to receive the same maintenance immunosuppressive therapy. DATA COLLECTION AND ANALYSIS: Two authors extracted data independently. RevMan analysis was used for statistical analysis of dichotomous data with risk ratio (RR), and of continuous data with mean difference (MD), both with 95% confidence intervals (CI). Methodological components were used to assess risks of systematic errors (bias). Trial sequential analysis was used to assess the risks of random errors (play of chance). We assessed mortality, acute rejection, infection, Cytomegalovirus (CMV) infection, post-transplantation lymphoproliferative disorder, cancer, adverse events, chronic allograft vasculopathy, renal function, hypertension, diabetes mellitus, and hyperlipidaemia. MAIN RESULTS: In this review, we included 22 RCTs that investigated the use of T-cell antibody induction, with a total of 1427 heart-transplant recipients. All trials were judged to be at a high risk of bias. Five trials, with a total of 606 participants, compared any kind of T-cell antibody induction versus no antibody induction; four trials, with a total of 576 participants, compared interleukin-2 receptor antagonist (IL-2 RA) versus no induction; one trial, with 30 participants, compared monoclonal antibody (other than IL-2 RA) versus no antibody induction; two trials, with a total of 159 participants, compared IL-2 RA versus monoclonal antibody (other than IL-2 RA) induction; four trials, with a total of 185 participants, compared IL-2 RA versus polyclonal antibody induction; seven trials, with a total of 315 participants, compared monoclonal antibody (other than IL-2 RA) versus polyclonal antibody induction; and four trials, with a total of 162 participants, compared polyclonal antibody induction versus another kind, or dose of polyclonal antibodies.No significant differences were found for any of the comparisons for the outcomes of mortality, infection, CMV infection, post-transplantation lymphoproliferative disorder, cancer, adverse events, chronic allograft vasculopathy, renal function, hypertension, diabetes mellitus, or hyperlipidaemia. Acute rejection occurred significantly less frequently when IL-2 RA induction was compared with no induction (93/284 (33%) versus 132/292 (45%); RR 0.73; 95% CI 0.59 to 0.90; I(2) 57%) applying the fixed-effect model. No significant difference was found when the random-effects model was applied (RR 0.73; 95% CI 0.46 to 1.17; I(2) 57%). In addition, acute rejection occurred more often statistically when IL-2 RA induction was compared with polyclonal antibody induction (24/90 (27%) versus 10/95 (11%); RR 2.43; 95% CI 1.01 to 5.86; I(2) 28%). For all of these differences in acute rejection, trial sequential alpha-spending boundaries were not crossed and the required information sizes were not reached when trial sequential analysis was performed, indicating that we cannot exclude random errors.We observed some occasional significant differences in adverse events in some of the comparisons, however definitions of adverse events varied between trials, and numbers of participants and events in these outcomes were too small to allow definitive conclusions to be drawn. AUTHORS' CONCLUSIONS: This review shows that acute rejection might be reduced by IL-2 RA compared with no induction, and by polyclonal antibody induction compared with IL-2 RA, though trial sequential analyses cannot exclude random errors, and the significance of our observations depended on the statistical model used. Furthermore, this review does not show other clear benefits or harms associated with the use of any kind of T-cell antibody induction compared with no induction, or when one type of T-cell antibody is compared with another type of antibody. The number of trials investigating the use of antibodies against T-cells for induction after heart transplantation is small, and the number of participants and outcomes in these RCTs is limited. Furthermore, the included trials are at a high risk of bias. Hence, more RCTs are needed to assess the benefits and harms of T-cell antibody induction for heart-transplant recipients. Such trials ought to be conducted with low risks of systematic and random error.

Antibody induction therapy for lung transplant recipients.

BACKGROUND: Lung transplantation has become a valuable and well-accepted treatment option for most end-stage lung diseases. Lung transplant recipients are at risk of transplanted organ rejection, and life-long immunosuppression is necessary. Clear evidence is essential to identify an optimal, safe and effective immunosuppressive treatment strategy for lung transplant recipients. Consensus has not yet been achieved concerning use of immunosuppressive antibodies against T-cells for induction following lung transplantation. OBJECTIVES: We aimed to assess the benefits and harms of immunosuppressive T-cell antibody induction with ATG, ALG, IL-2RA, alemtuzumab, or muromonab-CD3 for lung transplant recipients. SEARCH METHODS: We searched the Cochrane Renal Group's Specialised Register to 4 March 2013 through contact with the Trials Search Co-ordinator using search terms relevant to this review. Studies contained in the Specialised Register are identified through search strategies specifically designed for CENTRAL, MEDLINE and EMBASE. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) that compared immunosuppressive monoclonal and polyclonal T-cell antibody induction for lung transplant recipients. An inclusion criterion was that all participants must have received the same maintenance immunosuppressive therapy within each study. DATA COLLECTION AND ANALYSIS: Three authors extracted data. We derived risk ratios (RR) for dichotomous data and mean differences (MD) for continuous data with 95% confidence intervals (CI). Methodological risk of bias was assessed using the Cochrane risk of bias tool and trial sequential analyses were undertaken to assess the risk of random errors (play of chance). MAIN RESULTS: Our review included six RCTs (representing a total of 278 adult lung transplant recipients) that assessed the use of T-cell antibody induction. Evaluation of the included studies found all to be at high risk of bias.We conducted comparisons of polyclonal or monoclonal T-cell antibody induction versus no induction (3 studies, 140 participants); polyclonal T-cell antibody versus no induction (3 studies, 125 participants); interleukin-2 receptor antagonists (IL-2RA) versus no induction (1 study, 25 participants); polyclonal T-cell antibody versus muromonab-CD3 (1 study, 64 participants); and polyclonal T-cell antibody versus IL-2RA (3 studies, 100 participants). Overall we found no significant differences among interventions in terms of mortality, acute rejection, adverse effects, infection, pneumonia, cytomegalovirus infection, bronchiolitis obliterans syndrome, post-transplantation lymphoproliferative disease, or cancer.We found a significant outcome difference in one study that compared antithymocyte globulin versus muromonab-CD3 relating to adverse events (25/34 (74%) versus 12/30 (40%); RR 1.84, 95% CI 1.13 to 2.98). This suggested that antithymocyte globulin increased occurrence of adverse events. However, trial sequential analysis found that the required information size had not been reached, and the cumulative Z-curve did not cross the trial sequential alpha-spending monitoring boundaries.None of the studies reported quality of life or kidney injury. Trial sequential analyses indicated that none of the meta-analyses achieved required information sizes and the cumulative Z-curves did not cross the trial sequential alpha-spending monitoring boundaries, nor reached the area of futility. AUTHORS' CONCLUSIONS: No clear benefits or harms associated with the use of T-cell antibody induction compared with no induction, or when different types of T-cell antibodies were compared were identified in this review. Few studies were identified that investigated use of antibodies against T-cells for induction after lung transplantation, and numbers of participants and outcomes were also limited. Assessment of the included studies found that all were at high risk of methodological bias.Further RCTs are needed to perform robust assessment of the benefits and harms of T-cell antibody induction for lung transplant recipients. Future studies should be designed and conducted according to methodologies to reduce risks of systematic error (bias) and random error (play of chance).