Age-Related Quality of Life in Cardiac Surgical Patients with Extracorporeal Life Support.

BACKGROUND: The rationale of the study was to analyze the impact of age on quality of life (QoL) in patients who had undergone cardiac surgery with consecutive extracorporeal life support (ECLS) treatment. METHODS: The study population consisted of 200 patients, operated upon between August 2006 and December 2018. The patient cohort was divided into two groups following an arbitrary cutoff age of 70 years. Comparative outcome analysis was calculated utilizing the European Quality of Life-5-Dimensions-5-Level Version (EQ-5D-5L). RESULTS: A total of 113 patients were 70 years or less old (group young), whereas 87 patients were older than 70 years (group old). In 45.7% of cases, the ECLS system was established during cardiogenic shock and external cardiac massage. The overall survival-to-discharge was 31.5% (n = 63), with a significantly better survival in the younger patient group (young = 38.9%; old = 21.8%, p = 0.01). Forty-two patients (66%) responded to the QoL survey after a median follow-up of 4.3 years. Older patients reported more problems with mobility (y = 52%; o = 88%, p = 0.02) and self-care (y = 24%; o = 76%, p = 0.01). However, the patients' self-rated health status utilizing the Visual Analogue Scale revealed no differences (y = 70% [50-80%]; o = 70% [60-80%], p = 0.38). Likewise, the comparison with an age-adjusted German reference population revealed similar QoL indices. There were no statistically significant differences in the EQ-5D-5L index values related to sex, number of comorbidities, and emergency procedures. CONCLUSION: Despite the limited sample size due to the high mortality rate especially in elderly, the present study suggests that QoL of elderly patients surviving ECLS treatment is almost comparable to younger patients.

Nivolumab plus Brentuximab vedotin +/- bendamustine combination therapy: a safe and effective treatment in pediatric recurrent and refractory classical Hodgkin lymphoma.

Introduction: Classical Hodgkin lymphoma (cHL) is the most common pediatric lymphoma. Approximately 10% of patients develop refractory or recurrent disease. These patients are treated with intensive chemotherapy followed by consolidation with radiotherapy or high-dose chemotherapy and autologous stem cell reinfusion. Although this treatment is effective, it comes at the cost of severe long-term adverse events, such as reduced fertility and an increased risk of secondary cancers. Recently, promising results of inducing remission with the immune checkpoint inhibitor nivolumab (targeting PD-1) and the anti-CD30 antibody-drug conjugate Brentuximab vedotin (BV) +/- bendamustine were published. Methods: Here we describe a cohort of 10 relapsed and refractory pediatric cHL patients treated with nivolumab + BV +/- bendamustine to induce remission prior to consolidation with standard treatment. Results and discussion: All patients achieved complete remission prior to consolidation treatment and are in ongoing complete remission with a median follow-up of 25 months (range: 12 to 42 months) after end-of-treatment. Only one adverse event of CTCAE grade 3 or higher due to nivolumab + BV was identified. Based on these results we conclude that immunotherapy with nivolumab + BV +/- bendamustine is an effective and safe treatment to induce remission in pediatric R/R cHL patients prior to standard consolidation treatment. We propose to evaluate this treatment further to study putative long-term toxicity and the possibility to reduce the intensity of consolidation treatment.

Thymus and activation-regulated chemokine (TARC) as treatment response marker for paediatric Hodgkin lymphoma: A pilot study.

Classical Hodgkin lymphoma (cHL) is characterised by malignant Hodgkin Reed-Sternberg cells located in an inflammatory microenvironment. Blood biomarkers result from active cross-talk between malignant and non-malignant cells. One promising biomarker in adult patients with cHL is thymus and activation-regulated chemokine (TARC). We investigated TARC as marker for interim and end-of-treatment response in paediatric cHL. In this multicentre prospective study, TARC levels were measured among 99 paediatric patients with cHL before each cycle of chemotherapy and were linked with interim and end-of-treatment remission status. TARC levels were measured by enzyme-linked immunosorbent assay. At diagnosis, TARC levels were elevated in 96% of patients. Plasma TARC levels declined significantly after one cycle of chemotherapy (p < 0.01 vs. baseline) but did not differ at interim assessment by positron emission tomography (p = 0.31). In contrast, median plasma TARC at end of treatment was significantly higher in three patients with progressive disease compared to those in complete remission (1.226 vs. 90 pg/ml; p < 0.001). We demonstrate that, in paediatric patients, plasma TARC is a valuable response marker at end-of-treatment, but not at interim analysis after the first two chemotherapy cycles. Further research is necessary to investigate TARC as marker for long-term progression free survival.

Sex-dependent deterioration of cardiac function and molecular alterations in age- and disease-associated RAGE overexpression.

Elevated expression of the receptor for advanced-glycation endproducts (RAGE) in cardiac tissue is well-known in the elderly, in diabetes mellitus, and after acute cardiac infarction or ischemia/reperfusion injuries. RAGE and its binding partners affect the clinical outcome of heart failure and may play an essential role in accelerating the functional decline in cardiovascular aging. Therefore, hearts of wild-type (WT) C57black6/N and cardiac-specific RAGE-overexpressing transgenic (TR) mice were analyzed for their function by ultrasound at young (4-5 months) and old (22-23 months) ages. Transgenic mice exhibit significantly increased systolic (LVD-sy) and diastolic (LVD-di) diameters of their left ventricles. The left ventricular ejection fraction (EF) was significantly reduced in young male TR mice. Omics of the heart did not reveal direct activation of cytokine-induced inflammation. Instead, energy metabolism-associated genes were enriched in downregulated transcripts and proteins of TR animals, causing decreased ATP production. In a sex-specific manner, there was a reduced expression of the four-and-a-half LIM-domains protein 2 (FHL2). In conclusion, transgene-induced RAGE overexpression, as a model for age- and disease-associated RAGE alteration, leads to a sex-dependent EF decline, in which FHL2 and energy depletion might play crucial roles.

ICU Readmission after Cardiac Surgery-Still a Matter of Concern?

BACKGROUND: Despite improvements in diagnostics and perioperative care, readmission to intensive care unit (ICU) after cardiac surgery is still a severe drawback for patients with considerable morbidity, mortality, and costs. Aim of this retrospective analysis was to disentangle independent risk factors for ICU readmission. MATERIAL AND METHODS: Between 01/2004 and 12/2012, 336 out of 9,555 (3.5%) patients undergoing cardiac surgery at the Department of Cardiothoracic Surgery in Regensburg (Germany) were readmitted to ICU. A matched-pair analysis (readmission vs control group) was conducted, matching for gender, age, and surgical procedure. Operations included coronary artery bypass grafting, valve reconstruction/replacement, aortic surgery, combined procedures, and others. Mean follow-up was 6.2 ± 2.3 years. RESULTS: Median age of the readmitted patients was 71 years (65; 76), and the majority was male (67.9%). Median logistic Euroscore as a parameter for perioperative risk was significantly higher as compared with the control group (5.8 vs 5.2, p = 0.045) as was the prevalence of comorbidities including hypertension, chronic obstructive pulmonary disease, prior myocardial infarction, stroke, and PAOD. Most common reasons for readmission were cardiopulmonary instability (27.4%), respiratory failure (20.8%), and surgery for deep sternal infection (8.6%). Twenty-one percent required more than one readmission. Overall mortality was significantly higher in readmitted patients (21.1 vs 12.5%). CONCLUSIONS: In conclusion, readmission to the ICU after cardiac surgery is a rare complication that is still associated with excessive mortality. Establishment of an intermediate care unit proved to be an excellent means to reduce ICU stay without endangering post-surgery patients and significantly reduced the ICU readmission rate.

The 'Weekend Effect' in adult patients who receive extracorporeal cardiopulmonary resuscitation after in- and out-of-hospital cardiac arrest.

AIM: This study investigates the potentially adverse association between extracorporeal cardiopulmonary resuscitation (ECPR) after cardiac arrest on weekends versus weekdays. METHODS: Single-centre, retrospective, stratified (weekday versus weekend) analysis of 318 patients who underwent in-hospital ECPR after out-of-hospital and in-hospital cardiac arrest (OHCA/IHCA) between 01/2008 and 12/2018. Weekend was defined as the period between Friday 17:00 and Monday 06:59. RESULTS: Seventy-three patients (23%) received ECPR during the weekend and 245 arrests (77%) occurred during the weekday. Whereas survival to discharge did not differ between both groups, long-term survival was significantly lower in the weekend group (p = 0.002). In the multivariate analysis, independent risk factors associated with hospital mortality were no flow time (OR 1.014; 95% CI 1.004-1.023) and serum lactate prior ECPR (OR 1.011; 95% CI 1.006-1.012), whereas each unit serum haemoglobin above average had a protective effect on in-hospital mortality (OR 0.87; 95% CI 0.79-0.96). New onset kidney failure requiring renal replacement therapy occurred more often in the weekend group (30.1% versus 18.4%; p = 0.04). One third of patients experienced complications regardless ECPR was initiated at weekdays or weekends. CONCLUSION: Extracorporeal cardiopulmonary resuscitation at weekends adversely seems to impact long-term survival regardless timing (dayshift/nightshift). Duration of CPR and serum lactate prior ECPR were demonstrated as independent risk factors for in-hospital mortality. As ECPR at weekends could not be shown to be an independent outcome predictor a thorough analysis of clinical events subsequent to this intervention is warranted to understand long-term consequences of ECPR initiation after cardiac arrest.

Bone Morphogenetic Protein-7 Enhances Degradation of Osteoinductive Bioceramic Implants in an Ectopic Model.

BACKGROUND: The aim of the present study was to evaluate the degradation pattern of highly porous bioceramics as well as the bone formation in presence of bone morphogenetic protein 7 (BMP-7) in an ectopic site. METHODS: Novel calcium phosphate ceramic cylinders sintered at 1,300°C with a total porosity of 92-94 vol%, 45 pores per inch, and sized 15 mm (Ø) × 5 mm were grafted on the musculus latissimus dorsi bilaterally in 10 Göttingen minipigs: group I (n = 5): hydroxyapatite (HA) versus biphasic calcium phosphate (BCP), a mixture of HA and tricalcium phosphate (TCP) in a ratio of 60/40 wt%; group II (n = 5): TCP versus BCP. A test side was supplied in situ with 250 µg BMP-7. Fluorochrome bone labeling and computed tomography were performed in vivo. Specimens were evaluated 14 weeks after surgery by environmental scanning electron microscopy, fluorescence microscopy, tartrate-resistant acid phosphatase, and pentachrome staining. RESULTS: Bone formation was enhanced in the presence of BMP-7 in all ceramics (P = 0.001). Small spots of newly formed bone were observed in all implants in the absence of BMP-7. Degradation of HA and BCP was enhanced in the presence of BMP-7 (P = 0.001). In those ceramics, osteoclasts were observed. TCP ceramics were almost completely degraded independently of the effect of BMP-7 after 14 weeks (P = 0.76), osteoclasts were not observed. CONCLUSIONS: BMP-7 enhanced bone formation and degradation of HA and BCP ceramics via osteoclast resorption. TCP degraded via dissolution. All ceramics were osteoinductive. Novel degradable HA and BCP ceramics in the presence of BMP-7 are promising bone substitutes in the growing individual.

BMP-7 Preserves Surface Integrity of Degradable-ceramic Cranioplasty in a Göttingen Minipig Model.

BACKGROUND: The aim of the study was to evaluate the integrity of a craniotomy grafted site in a minipig model using different highly porous calcium phosphate ceramic scaffolds either loaded or nonloaded with bone morphogenetic protein-7 (BMP-7). METHODS: Four craniotomies with a diameter of 15 mm (critical-size defect) were grafted with different highly porous (92-94 vol%) calcium phosphate ceramics [hydroxyapatite (HA), tricalcium phosphate (TCP), and biphasic calcium phosphate (BCP; a mixture of HA and TCP)] in 10 Göttingen minipigs: (a) group I (n = 5): HA versus BCP; (b) group II (n = 5): TCP versus BCP. One scaffold of each composition was supplied with 250 µg of BMP-7. In vivo computed tomography scan and fluorochrome bone labeling were performed. Specimens were evaluated 14 weeks after surgery by environmental scanning electron microscopy, fluorescence microscopy, and Giemsa staining histology. RESULTS: BMP-7 significantly enhanced bone formation in TCP (P = 0.047). Slightly enhanced bone formation was observed in BCP (P = 0.059) but not in HA implants. BMP-7 enhanced ceramic degradation in TCP (P = 0.05) and BCP (P = 0.05) implants but not in HA implants. Surface integrity of grafted site was observed in all BMP-7-loaded implants after successful creeping substitution by the newly formed bone. In 9 of 10 HA implants without BMP-7, partial collapse of the implant site was observed. All TCP implants without BMP-7 collapsed. Fluorescent labeling showed bone formation at week 1 in BMP-7-stimulated implants. CONCLUSIONS: BMP-7 supports bone formation, ceramic degradation, implant integration, and surface integrity of the grafted site.

Long-term survival and quality of life after extracorporeal life support: a 10-year report.

OBJECTIVES: Information is lacking about long-term survival and quality of life (QOL) after treating patients on extracorporeal life support. METHODS: Outcome data were assessed by phone interviews, a QOL analysis using the EuroQol 5-dimensions questionnaire and a retrospective inquiry of the Regensburg ECMO Registry database for the decade 2006-2015. A statistical analysis was obtained by comparing patients with a cardiosurgical intervention (CS = 189 patients) with those without (w/oCS = 307 patients). RESULTS: Survival to discharge in the w/oCS group was higher than that in the CS group (w/oCS: 41.7% vs CS: 29.5%; P = 0.004). A Kaplan-Meier analysis showed a significant difference between both groups in favour of patients w/oCS (log rank P = 0.02). This difference was no longer statistically significant after propensity score matching ( P = 0.07). The 1- and 2-year survival rates of discharged patients were 67% and 50% in the w/oCS group vs 60% and 45% in the CS group (log rank P = 0.29). Eighty-two patients answered the QOL questionnaire after a mean follow-up time of 4.2 ± 2.9 years. A total of 75% could handle their daily life; 57% were not limited in their usual activities. Mobility impairment was noted in 50%; 25% returned to work or school. There were no differences in the EuroQol 5-dimension indices between the patient groups. However, compared to a normative age-matched population, significantly lower indices were calculated. CONCLUSIONS: Long-term survival rates in patients requiring extracorporeal life support are acceptable with a probable advantage for patients without an operation and a narrowed QOL. The results are promising and encouraging, but there is also a need for improvement.

Patients under Psychiatric Medication Undergoing Cardiac Surgery Have a Higher Risk for Adverse Events.

Objective The percentage of patients undergoing cardiac surgery under some sort of psychiatric medication (PM) is not negligible. Thus, this study aimed to evaluate a possible impact of preoperative PM on the outcome after cardiac surgery. Methods A matched case-control study was conducted by including all patients who underwent myocardial revascularization and/or surgical valve operation in our institution from December 2008 till February 2011 by chart review and institutional quality assurance database (QS) analysis. Results Out of 1,949 patients included, 184 patients (9%) were identified with PM medication (group A). A control group matched for logistic EuroSCORE II, ejection fraction and age was generated (group C). Patients with PM were in mean significantly longer on the intensive care unit (A: 4.94 days; 95% confidence interval (CI), 3.9-5.9 days vs. C: 3.24 days; CI, 2.84-3.64 days; p = 0.003), had longer mechanical ventilation times (A: 36.70 hours; CI, 19.81-53.59 hours vs. C: 20.14 hours; CI, 14.61-25.68 hours; p = 0.258), and significantly more episodes of respiratory insufficiencies (A: 31 episodes [17%] vs. C: 17 episodes [9%]; p = 0.002). Regression analysis revealed preoperative PM as a significant risk factor for respiratory insufficiency (odds ratio: 1.99, CI: 1.0-3.74; p = 0.04). Chest tube drainage (A: 690 mL, CI: 571-808 mL vs. C: 690 mL; CI: 496-884 mL, p = 0.53) and the total amount of red blood cell transfusion units were similar (A: 1.69 units; CI: 1.21-2.18 units vs. C: 1.50 units; CI: 1.04-1.96 units; p = 0.37). Sternal dehiscence requiring sternal refixation was significantly more frequent in A (12 patients [7%] vs. C: 2 patients [1%]; odds ratio: 6.3, CI: 1.4-28.7; p = 0.01). The 30-day mortality was similar in both groups (A: 6 patients [3%] vs. C: 4 patients [2%]; odds ratio: 1.5; CI: 0.4-5.4; p = 0.5); however, the 100-day mortality was near significantly higher in group A (A: 14 patients (8%) vs. C: 6 patients (3%); odds ratio: 2.4, CI: 0.9-6.5, p = 0.057). Conclusion Patients with preoperative PM developed complications more frequently compared with a matched control group. The underlying multifactorial mechanisms remain unclear. Patients under PM need to be identified and particular care including optimal pre- and postoperative psychiatric assistance is recommended.

Minimized extracorporeal circulation is improving outcome of coronary artery bypass surgery in the elderly.

Advanced age is a known risk factor for morbidity and mortality after coronary artery bypass grafting (CABG). Minimized extracorporeal circulation (MECC) has been shown to reduce the negative effects associated with conventional extracorporeal circulation (CECC). This trial assesses the impact of MECC on the outcome of elderly patients undergoing CABG. Eight hundred and seventy-five patients (mean age 78.35 years) underwent isolated CABG using CECC (n=345) or MECC (n=530). The MECC group had a significantly shorter extracorporeal circulation time (ECCT), cross-clamp time and reperfusion time and lower transfusion needs. Postoperatively, these patients required significantly less inotropic support, fewer blood transfusions, less postoperative hemodialysis and developed less delirium compared to CECC patients. In the MECC group, intensive care unit (ICU) stay was significantly shorter and 30-day mortality was significantly reduced [2.6% versus 7.8%; p<0.001]. In conclusion, MECC improves outcome in elderly patients undergoing CABG surgery.

Impact of Acute Kidney Injury on Outcome in Patients With Severe Acute Respiratory Failure Receiving Extracorporeal Membrane Oxygenation.

OBJECTIVES: Extracorporeal lung support is currently used in the treatment of patients with severe respiratory failure until organ recovery and as a bridge to further therapeutic modalities. The aim of our study was to evaluate the impact of acute kidney injury on outcome in patients with acute respiratory distress syndrome under venovenous extracorporeal membrane oxygenation support and to analyze the association between prognosis and the time of occurrence of acute kidney injury and renal replacement therapy initiation. DESIGN: Retrospective observational study. SETTING: A large European extracorporeal membrane oxygenation center, University Medical Center Regensburg, Germany. PATIENTS: A total of 262 consecutive adult patients with acute respiratory distress syndrome have been treated with extracorporeal membrane oxygenation between January 2007 and May 2012. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Patient median age was 49 years (range, 18-78 yr); 183 (69.8%) were male. The leading cause of lung failure was pneumonia. The median Sequential Organ Failure Assessment score was 12.0 (8.8-15.0), and the median lung injury score was 3.3 (3.3-3.7). The median extracorporeal membrane oxygenation support duration was 9 days (6-15 d). One hundred eighty-three patients (69.8%) were successfully weaned and 156 patients (59.9%) survived to hospital discharge. One hundred thirty-one patients (50.0%) were treated with renal replacement therapy during extracorporeal membrane oxygenation support. The survival rate was significantly lower in patients requiring renal replacement therapy compared with those without renal replacement therapy (47.3% vs 71.8%; p < 0.001) overall. The Kaplan-Meier survival curves differed significantly for patients without renal replacement therapy versus patients with renal replacement therapy prior to extracorporeal membrane oxygenation support (p = 0.003). Furthermore, the multivariate logistic regression analysis suggests that the necessity of renal replacement therapy prior to extracorporeal membrane oxygenation insertion was an independent risk factor for mortality (95% CI, 0.77-0.88; p < 0.001). However, the necessity of renal replacement therapy during extracorporeal membrane oxygenation support was not an independent risk factor for mortality in these patients (p = 0.37). CONCLUSIONS: Acute kidney injury is a major complication in acute respiratory distress syndrome probably mirroring severe systemic disease. In our cohort, development of acute kidney injury requiring renal replacement therapy prior to extracorporeal membrane oxygenation insertion was negatively associated with survival, whereas acute kidney injury that developed during extracorporeal membrane oxygenation support was not.

Re-exploration for bleeding or tamponade after cardiac surgery: impact of timing and indication on outcome.

OBJECTIVES: Re-exploration after cardiac surgery remains a frequent complication with adverse outcomes. The aim of this study was to evaluate the impact of timing and indication of re-exploration on outcome. METHODS: A retrospective, observational study on a cohort of 209 patients, who underwent re-exploration after cardiac surgery between January 2005 and December 2011, was performed. The cohort was matched for age, gender, and procedure with patients who were not re-explored during the same period. RESULTS: The intraoperative and postoperative transfusion requirements were higher in the re-exploration group (p < 0.01). Patients in the re-exploration group had significantly higher incidences of postoperative acute renal injury (10.0 vs. 3.3%), sternal wound (9.1 vs. 2.4%) and pulmonary (13.4 vs. 4.3%) infections, longer ventilation time (22 [range, 14-52] vs. 12 [range, 9-16] hours) and intensive care unit stay (5 [range, 3-7] vs. 2 [range, 2-4] days), and higher mortality rate (9.6 vs. 3.3%). However, the multivariate logistic regression analysis demonstrated that not the re-exploration itself, but the deleterious effects of re-exploration (blood loss and transfusion requirement) were independent risk factors for mortality. Mortality was 5.3% for patients who were re-explored within the first 12 hours and 20.3% for patients who were re-explored after 12 hours (p = 0.003). Mortality was 3.6% for patients with bleeding and 31.4% for patients with cardiac tamponade for indication of re-exploration (p < 0.001). CONCLUSIONS: This study suggests that re-exploration after cardiac surgery is associated with increased mortality and morbidity. Patients with delayed re-exploration and suffering from cardiac tamponade have adverse outcome.

Assessment of cisplatin concentration and depth of penetration in human lung tissue after hyperthermic exposure.

OBJECTIVES: The effects of cisplatin on the lung parenchyma during hyperthermic intrathoracic chemotherapy perfusion have not been analysed in detail. The objective of this study was to evaluate both the concentration and depth of the penetration of cisplatin in human lung tissue after hyperthermic exposure under ex vivo conditions. METHODS: This experimental study was approved by the local ethics committee. Twelve patients underwent pulmonary wedge resections after elective thoracic lobectomies were performed (resected lobe), and the lung tissue (approximately 1-2 cm(3)) was incubated (in vitro) with cisplatin (0.05 mg/ml; 60 min, 42°C). Subsequent tissue beds (depth, 0.5 mm; median weight, 70-92 mg) were prepared from the outside to the middle, and the amount of cisplatin per tissue weight was analysed using atomic absorption spectrometry. Afterwards, the penetration of cisplatin depth was calculated and related to the different concentrations per tissue. RESULTS: Cisplatin penetrated into the human lung tissue after ex vivo hyperthermic exposure. The median amount of platinum [nmol cisplatin/g lung tissue] decreased significantly (P ≤ 0.05) depending on the penetration depth: 32 nmol/g (1 mm), 20 nmol/g (2 mm) and 6.8 nmol/g (4 mm). The calculated median concentrations of cisplatin (µg/ml) were 2.4 µg/ml (1 mm), 1.4 µg/ml (2 mm) and 0.5 µg/ml (4 mm), respectively. CONCLUSIONS: Under ex vivo hyperthermic conditions, cisplatin diffused into human lung tissue. The median penetration depth of the cisplatin was approximately 3-4 mm. The penetration of cisplatin into lung tissue may affect the local therapy of residual tumour cells on the lung surface using hyperthermic intrathoracic chemotherapy perfusion in patients with malignant pleural tumours.

Impact of age on early outcome after coronary bypass graft surgery using minimized versus conventional extracorporeal circulation.

BACKGROUND: Objective of this study was to evaluate the impact of age on comparative early outcomes after coronary artery bypass graft surgery (CABG) with minimized (MECC) and conventional extracorporeal circulation (CECC). METHODS: A retrospective age-, gender- and operation-matched cohort analysis between January 2005 and December 2010 with a total of 2274 patients undergoing CABG with MECC (n = 1137; 50%) or CECC was performed. Patients were stratified into 4 groups according to age: <59 years, 60-69 years, 70-79 years, and 80 years of age or older. Outcomes were compared within each age group. Patients with preoperative dialysis were excluded from analysis. Primary endpoint was 30-day mortality. RESULTS: Patients treated with CECC had a significantly higher mean logistic EuroSCORE (6.3% vs. 5.0%; p < 0.001), a slightly lower rate of preoperative myocardial infarction (46% vs. 51%; p = 0.01) and a higher rate of impaired renal function (eGFR < 60 mL/min/1.73 m2: 24% vs. 20%; p = 0.01) compared to MECC-patients. Left internal mammary artery was significantly used more often in MECC patients (93% vs. 86%; p < 0.001). Cardiopulmonary bypass and aortic-cross clamping time were significantly lower in the MECC group (p < 0.001). Overall 30-day mortality was significantly higher in patients treated with CECC (4.4% vs. 2.2%; p = 0.002). Within the different age groups mortality rates were not significantly different except for patients aged 60-69 years (4.5% vs. 1.8%; p = 0.03). Postoperative requirement of renal replacement therapy (4% vs. 2.2%; p = 0.01), respiratory insufficiency (9.9% vs. 6.6%; P = 0.004) and incidence of low cardiac output syndrome (3% vs. 1.2%; p = 0.003) were significantly increased in patients with CECC. Multivariate analysis identified age (p = 0.005; 95% CI 1.01 to 1.08; OR 1.05) among other parameters as an independent risk factor, whereas conventional extracorporeal circulation itself did not present as an independent risk factor for 30-day mortality. CONCLUSIONS: In this matched study sample early outcome was significantly better in patients with MECC compared to CECC, irrespective of age. Prior myocardial infarction estimated GFR < 60 mL and waiving the use of LIMA were independent risk factors for 30-day mortality, which were more present in the CECC group.

Prospective, comparative study of the On-Q® PainBuster® postoperative pain relief system and thoracic epidural analgesia after thoracic surgery.

OBJECTIVE: Pain after thoracotomy is associated with intense discomfort leading to impaired pulmonary function. DESIGN: Prospective, non-randomized trial from April 2009 to September 2011. SETTING: Department of Thoracic Surgery, single-center. PARTICIPANTS: Thoracic surgical patients. INTERVENTIONS: Comparison of thoracic epidural analgesia (TEA) with the On-Q® PainBuster® system after thoracotomy. MEASUREMENTS AND MAIN RESULTS: The TEA group (n=30) received TEA with continuous 0.2% ropivacaine at 4 mL-to-8 mL/h, whereas Painbuster® patients (n=32) received 0.75% ropivacaine at 5 mL/h until postoperative day 4 (POD4). Basic and on-demand analgesia were identical in both groups. Pain was measured daily on a numeric analog scale from 0 (no pain) to 10 (worst pain) at rest and at exercise. There were no significant differences regarding demographic and preoperative data between the groups, but PainBuster® patients had a slightly lower relative forced expiratory volume in 1 second (FEV1) (71±20% versus 86±21%; p=0.01). Most common surgical procedures were lobectomies (38.8%) and atypical resections (28.3%) via anterolateral thoracotomy. Most common primary diagnoses were lung cancer (48.3%) and tumor of unknown origin (30%). At POD1, median postoperative pain at rest was 2.1 (1; 2.8) in the TEA group and 2 (1.5; 3.8; p=0.62) in the PainBuster® group. At exercise, median pain was 4.3 (3.5; 3.8) in the TEA group compared to 5.0 (4.0; 6.5; p=0.07). Until POD 5 there were decreases in pain at rest and exercise but without significant differences between the groups. CONCLUSIONS: Sufficient analgesia after thoracotomy can be achieved with the intercostal PainBuster® system in patients, who cannot receive TEA.

D-dimers as an early marker for oxygenator exchange in extracorporeal membrane oxygenation.

PURPOSE: Early markers of oxygenator dysfunction during prolonged use of extracorporeal membrane oxygenation (ECMO) are important for timely exchange to avoid sudden loss of function due to clot formation within the system. The measurement of D-dimers (DDs) in plasma might be a marker for early diagnosis of thrombus formation and dysfunction of heparin-coated membrane oxygenators (MOs). METHODS: This is a retrospective study on prospectively collected data of 24 adult acute respiratory distress syndrome patients requiring long-term veno-venous ECMO with at least 1 MO exchange. Kinetics of coagulation, inflammation, and oxygenator function were analyzed before and after MO exchange. RESULTS: Median (interquartile range) support duration is 20 (15-29) days. Thirty-four MOs had to be replaced. Exchange occurred due to visible thrombus formation in the MO (n=16), worsening gas exchange (n=11), increased blood flow resistance (n=1), and activation of coagulation with diffuse bleeding (n=6). In 15 cases, DDs were continuously elevated and, therefore, not suitable as marker for MO exchange. In the remaining 19 cases, DDs increased significantly within 3 days before exchange from 15 (9-20) to 30 (21-35) mg/dL (P=.002) and declined significantly within 1 day thereafter to 13 (7-17) mg/dL (P=.003). CONCLUSIONS: An increase in plasma DD concentration in absence of other explaining pathology can be helpful in predicting an MO exchange in miniaturized heparin-coated ECMO systems.

Impact of cardiopulmonary bypass on acute kidney injury following coronary artery bypass grafting: a matched pair analysis.

BACKGROUND: Postoperative Acute Kidney Injury (AKI) after coronary artery bypass grafting (CABG) is a common complication associated with significant morbidity and mortality. Cardiopulmonary bypass (CPB) is accepted to contribute to the occurrence of AKI and is of particular importance as it can be avoided by using the off-pump technique. However the renoprotective properties of off-pump (CABG) are controversial. This analysis evaluates the impact of cardiopulmonary bypass on renal function. METHODS: A matched-pair analysis of 1428 patients undergoing coronary artery bypass grafting was conducted. The patients were stratified according to their preoperative renal function and to risk factors for postoperative AKI. The development of the glomerular filtration rate (GFR) from before surgery until hospital discharge was analyzed. Incidence of AKI were analyzed. Furthermore the impact of CPB duration on postoperative GFR was assessed. RESULTS: The occurrence of AKI increases the risk of thirty-day mortality (odds ratio of 4.3). The postoperative GFR decreases significantly after coronary artery bypass grafting but does not differ between onpump and offpump CABG (60.2 ± 24.5 vs 60.7 ± 24.8; p=0.54). No difference regarding the incidence (26.6% vs 25%) and severity of AKI between cardiopulmonary bypass and the off-pump technique could be found. Duration of cardiopulmonary bypass does not correlate with the decline in postoperative glomerular filtration rate (Pearson Product Moment Correlation; p>0.050). CONCLUSION: Neither the mere use nor duration of cardiopulmonary bypass proofed to be a risk factor for developing postoperative AKI in CABG patients with a comparable preoperative risk profile for postoperative renal dysfunction. Furthermore, the severity of postoperative AKI is not affected by the use of cardiopulmonary bypass.

Extended surgical resections of advanced thymoma Masaoka stages III and IVa facilitate outcome.

OBJECTIVE: Extended thymoma resections including adjacent structures and pleurectomy/decortication (P/D) with hyperthermic intrathoracic chemotherapy (HITHOC) perfusion were performed in a multidisciplinary treatment regime. PATIENTS AND METHODS: Between July 2000 and February 2012, 22 patients with Masaoka stage III (n = 9; 41%) and Masaoka stage IVa (n = 13; 59%) thymic tumors were included. RESULTS: Mean age was 55 years (25-84 years) and 50% (11 out of 22) of patients were female. World Health Organization histological classification was as follows: B2 (n = 15), A (n = 1), B1 (n = 1), B3 (n = 2), and thymic carcinoma (C; n = 3). Radical thymectomy and partial resection of the mediastinal pleura and pericardium were performed. Of the 13, 9 patients with pleural involvement (stage IVa) received radical P/D followed by HITHOC (cisplatin). Macroscopic complete resection (R0/R1) was achieved in 19 (86%) patients. All patients received multimodality treatment depending on tumor stage, histology, and completeness of resection. Thirty-day mortality was 0% and three (13.6%) patients needed operative revision. Recurrence of thymoma was documented in five (22.7%) patients (stage III, n = 1; stage IVa, n = 4). Mean disease-free interval of patients with complete resection (n = 14 out of 22) was 30.2 months. After a mean follow-up of 29 months, 18 out of the 22 (82%) patients are alive. After P/D and HITHOC, 89% (8 out of 9 patients) are alive (current median survival is 25 months) without recurrence. CONCLUSIONS: Extended surgical resection of advanced thymic tumors infiltrating adjacent structures (stage III) or with pleural metastases (stage IVa) is safe and feasible. It provides a low recurrence rate and an acceptable survival. Additional HITHOC in patients with pleural thymoma spread seems to offer a better local tumor control.

The receptor for advanced glycation end-products supports lung tissue biomechanics.

The receptor for advanced glycation end-products (RAGE) and its soluble forms are predominantly expressed in lung but its physiological importance in this organ is not yet fully understood. Since RAGE acts as a cell adhesion molecule, we postulated its physiological importance in the respiratory mechanics. Respiratory function in a buffer-perfused isolated lung system and biochemical parameters of the lung were studied in young, adult, and old RAGE knockout (RAGE-KO) mice and wild-type (WT) mice. Lungs from RAGE-KO mice showed a significant increase in the dynamic lung compliance and a decrease in the maximal expiratory air flow independent of age-related changes. We also determined lower mRNA and protein levels of elastin in lung tissue of RAGE-KO mice. RAGE deficiency did not influence the collagen protein level, lung capillary permeability, and inflammatory parameters (TNF-α, high-mobility group box protein 1) in lung. Overexpressing RAGE as well as soluble RAGE in lung fibroblasts or cocultured lung epithelial cells increased the mRNA expression of elastin. Moreover, immunoprecipitation studies indicated a trans interaction of RAGE in lung epithelial cells. Our findings suggest the physiological importance of RAGE and its soluble forms in supporting the respiratory mechanics in which RAGE trans interactions and the influence on elastin expression might play an important role.