Results of open heart surgery in Jehovah's Witnesses patients.

AIM: The aim of this paper was to evaluate the results in patients from the religious community of Jehovah's Witnesses (JW) undergoing open heart surgery. METHODS: Between January 1998 and November 2007, 35 patients with a religious background of JW church underwent open heart surgery at the Department of Cardiothoracic Surgery, Medical University of Vienna (Austria). Eighteen patients underwent coronary artery bypass graft (CABG), 11 patients underwent valve surgery and 5 patients underwent combined procedures. One patient underwent isolated ascending aortic replacement. Five patients undergoing CABG were operated without cardiopulmonary bypass (CBP). RESULTS: Mean baseline hematocrit serum levels were 35.8+/-6.3%. The mean decrease of hematocrit serum levels was 20.0+/-21.1% after surgery. The mean decrease of hematocrit serum levels in patients undergoing CABG without CPB was 12.5+/-5.4% and 12.0+/-20.0% in patients after isolated valve replacement. One patient died during the operation. Four patients died in the postoperative period due to anemia. During follow-up, being 34.6+/-34.8 months to date, no cardiovascular related adverse event has been observed. CONCLUSIONS: The decrease of hematocrit serum levels is significantly characterizing the postoperative period of open heart surgery in JW. In patients undergoing CABG without CPB and in patients undergoing isolated valve replacement, decrease of hematocrit serum levels was lowest. Therefore, these techniques should be considered for first choice when appropriate. Furthermore, highly normal preoperative hematocrit serum levels and a meticulous surgical technique remain the mainstay of therapy in these patients.

Bail-out visceral bypass grafting for acute intestinal ischemia after endovascular stent-graft placement in a complicated type B dissection.

We report on the case of a 35-year-old male who underwent emergency stent-graft placement in March 2007 due to a complicated type B dissection. One week after this procedure the patient developed critical visceral malperfusion. Subsequently, autologous iliaco-mesenteric as well as iliaco-hepatic bypass grafting was performed. At 6-month follow-up, aortic remodelling has occurred and visceral perfusion is regular.

Secretion of soluble ST2 - possible explanation for systemic immunosuppression after heart surgery.

BACKGROUND: Cardiopulmonary bypass is known to affect cytokine release leading to a generalized endogenous immune reaction similar to that described in sepsis, without having been explored in great detail. Therefore we evaluated the anti- and pro-inflammatory cytokine responses after heart surgery. METHODS: 16 patients who underwent coronary artery bypass graft (CABG) surgery with extracorporeal circulation were included. ST2, IL-4 and IL-10 served as markers for TH2 cytokine response; IL-6, IL-8 and IFN-gamma as TH1 markers. Furthermore, total immunoglobulin subtype analysis (IgM, IgG, IgE) was performed. RESULTS: Serum levels of soluble ST2 started to climb at 60 minutes (from 38 +/- 14 preoperatively to 1 480 +/- 890 pg/ml) and peaked 24 hours after surgery (13 360 +/- 2 840 pg/ml, P < 0.001). IL-10 reached a maximum at 60 minutes and returned to baseline levels 24 hours later. IL-6 and IL-8 levels peaked 60 minutes after surgery. IL-4 and IFN-gamma did not change. Only IgM showed a significant peak on day eight ( P < 0.001). CONCLUSION: Our results demonstrate that CABG surgery induces a massive long-lasting secretion of ST2, a protein related to immune suppression.

Development of proteinuria after switch to sirolimus-based immunosuppression in long-term cardiac transplant patients.

Calcineurin-inhibitor therapy can lead to renal dysfunction in heart transplantation patients. The novel immunosuppressive (IS) drug sirolmus (Srl) lacks nephrotoxic effects; however, proteinuria associated with Srl has been reported following renal transplantation. In cardiac transplantation, the incidence of proteinuria associated with Srl is unknown. In this study, long-term cardiac transplant patients were switched from cyclosporine to Srl-based IS. Concomitant IS consisted of mycophenolate mofetil +/- steroids. Proteinuria increased significantly from a median of 0.13 g/day (range 0-5.7) preswitch to 0.23 g/day (0-9.88) at 24 months postswitch (p = 0.0024). Before the switch, 11.5% of patients had high-grade proteinuria (>1.0 g/day); this increased to 22.9% postswitch (p = 0.006). ACE inhibitor and angiotensin-releasing blocker (ARB) therapy reduced proteinuria development. Patients without proteinuria had increased renal function (median 42.5 vs. 64.1, p = 0.25), whereas patients who developed high-grade proteinuria showed decreased renal function at the end of follow-up (median 39.6 vs. 29.2, p = 0.125). Thus, proteinuria may develop in cardiac transplant patients after switch to Srl, which may have an adverse effect on renal function in these patients. Srl should be used with ACEi/ARB therapy and patients monitored for proteinuria and increased renal dysfunction.

Donor myocardial HIF-1alpha is an independent predictor of cardiac allograft dysfunction: a 7-year prospective, exploratory study.

Knowledge on interplay between the cardiac molecular response to transplantation-induced stress and primary graft dysfunction (PGD) is limited. A cDNA array identified HIF-1, EGR-1, NAB-2, VEGF-A and uPA as mediators of cardiac tissue response to transplantation-induced stress. mRNA expression of these molecules was measured in left ventricular biopsies from 200 donors before and after aortic cross-clamping and at 10-, 30- and 60-min reperfusion by real-time RT-PCR. HIF-1alpha expression at two time points was significantly associated with PGD, as shown by univariate analysis, receiver operating characteristic curve and multivariate logistic regression. At a cut-off level of 200 arbitrary units, HIF-1alpha after aortic cross-clamping in donors (78% sensitivity, 83% specificity) and at 10-min reperfusion (85% sensitivity, 83% specificity) identified PGD. HIF-1alpha demonstrates the potential to be a predictive marker for PGD; however, as multiple factors were tested at different time points, prospective evaluation is clearly necessary to confirm this observation.

[Vacuum assisted closure therapy for the treatment of sternal wound infections after heart transplantation: preliminary results]. / VAC-Therapie zur Behandlung von sternalen Wundinfektionen nach Herztransplantation: Erste Ergebnisse.

Sternal wound infection after heart transplantation is a feared and potentially life threatening complication with reported incidences between 2.5 % and 3.6 %. However, optimal therapy of sternal wound infections in heart transplant recipients remains a matter of controversy, particularly the effect of immunosuppression in those patients is still unclear. We examined 5 heart transplanted patients (4 men and 1 woman with a median age of 46 +/- 21.4 years (ranging from 14 to 59 years) in terms of inflammation and treatment response during VAC therapy. Infection begin was median 18.2 days (+/- 10 days, ranging from 5 to 28 days) after transplantation. VAC therapy lasted on average 12.2 +/- 2 days, ranging from 10 to 19 days. A median of 3 changes (range from 3 to 5) were necessary until the definitive closure. We examined C-reactive protein, leucocyte count and fibrinogen 2 days pre VAC, during VAC treatment and 2 days after definitive closure. All five patients showed an increase of leucocytes at every VAC change. Furthermore, we saw an adequate reaction to the VAC in terms of granulation tissue growth and resolution of infection. Transplanted patients had an increase of leucocytes at every VAC change. Furthermore all patients showed an adequate response of VAC treatment in terms of granulation tissue in growth and infection decline. Therefore a reduction of immunosuppressive therapy is not necessary, which in turn would increase the risk of rejection.

Elevated levels of interleukin-1beta-converting enzyme and caspase-cleaved cytokeratin-18 in acute myocardial infarction.

BACKGROUND: Systemic inflammation and apoptosis-specific immune activation play a major role in acute coronary syndromes (ACS) including acute myocardial infarction (AMI). The role of systemic and coronary obtained inflammatory plasma protein interleukin-1beta precursor (IL-1betap), IL-1beta-converting enzyme (ICE) and the apoptosis-specific caspase-cleaved cytokeratin-18 (ccCK-18) are not known in ACS. MATERIALS AND METHODS: Plasma samples were obtained from stable angina (SA, n = 34), unstable angina (UA, n = 37) and patients with AMI (n = 39). Coronary blood was acquired by means of thrombectomy devices (X-sizer) in AMI patients. IL-1betap, ICE and ccCK-18 were determined by enzyme-linked immunosorbent assay (ELISA). Group comparisons were evaluated by parametric Tukey test. Multivariate logistic regression analysis was performed to determine predictive values of IL-1betap, ICE and ccCK-18 as compared to creatine kinase (CK) and troponin T (TnT) in order to relate these markers with the occurrence of myocardial damage. RESULTS: IL-1betap, ICE and ccCK-18 were identified to be significantly altered in the peripheral blood of patients suffering from AMI as compared to SA and UA. ROC curves were plotted and revealed that ccCK-18 is a novel sensitive marker for the detection of myocardial damage as compared to TnT or CK. (AUC ccCK-18 0.925, TnT AUC 0.62 and CK AUC 0.858.) Moreover, ICE and ccCK-18 were significantly increased at the site of coronary occlusion as compared to peripheral blood samples in AMI patients (both P < 0.001). CONCLUSION: Our data suggest that ACS is related to increased concentration of systemic soluble ICE and ccCK-18. Moreover, soluble ccCK-18 was identified to be a superior marker as compared to TnT or CK, for detection of myocardial damage.

Treatment of an acute type B dissection with an intramural haematoma in the ascending aorta by percutaneous endovascular stent-graft placement.

Acute type B dissections accompanied by an intramural haematoma in the ascending aorta are rare. However, progression of the intramural haematoma in the ascending aorta poses risks for the patients, which are similar to those of type A dissections, including pericardial effusions and consecutive tamponade. To date, no clear treatment guidelines exist for these patients. We report on successful percutaneous endovascular stent-graft treatment of an acute type B dissection accompanied by an intramural haematoma in the ascending aorta as primary and sole form of treatment.

Recovery from giant cell myocarditis with ECMO support and utilisation of polyclonal antithymocyte globulin: a case report.

Giant cell myocarditis (GCM) is a rare and frequently fatal disorder. Patients suffer of ventricular arrhythmias or congestive heart failure. Here we describe a patient with cardiogenic shock and histological verified GCM. The patient was saved by implantation of extracorporeal membrane oxygeneation (ECMO) device and concomitant application of Rabbit antithymocyte globuline (rATG, Thymoglobulin, Sangstat), cyclosporine, and steroids in the acute event. 12 months after the crisis the patient evidences NYHA class I heart function and only a moderate impairment of heart function (EF 55%). The novel utilisation of ECMO in GCM related cardiogenic shock and application of rATG have prooven life-saving in this patient. Studies utilizing rATG in the treatment of GCM are warrented.

[Cost effectiveness of V.A.C. therapy after post-sternotomy mediastinitis]. / Kosteneffektivität der V.A.C.-Therapie nach Poststernotomie Mediastinitis.

Since November 2001 all patients with postoperative sternum bone infections were treated with V.A.C. therapy. The mean length of stay at intensive care unit was reduced from 9 to 1 day and reduces costs for 33 714.- USD per patient. Additionally patients who had to be closed with pectoralis muscle flap had significant reduced length of stay at ICU (1 vs 4 days, cost effectiveness 14 984.- USD per patient). The V.A.C. therapy after post-sternotomy mediastinitis significantly reduces morbidity and mortalità and is cost effective.

Mid-term results of conservative, conventional and endovascular treatment for acute traumatic aortic lesions.

BACKGROUND: To analyze our results after conservative, conventional and endovascular treatment for acute traumatic aortic lesions during the last decade. METHODS: From June 1993 to September 2004, a total of 19 patients with traumatic aortic lesions were referred to our department. All patients sustained injuries from blunt deceleration trauma. In hemodynamically stable patients, initial evaluation was by multi-slice CT scan. The diagnosis of traumatic aortic injury was confirmed and an individual treatment strategy was determined. In hemodynamically unstable patients, emergency thoracotomy was performed. RESULTS: An emergency thoracotomy was performed in seven (37%) patients. Mortality in this group was 100%. In the remaining group of 12 (63%) patients without hemodynamic instability at time of admission, in-hospital mortality was 0%. Treatment was surgical in five patients (26%), endovascular in five (26%) and conservative in two patients (11%). Mean follow-up was 63 months (5-108 months). No patient died during follow-up. In patients treated by endovascular stent-graft placement no signs of endoleaks could be detected. CONCLUSIONS: Hemodynamic stability and an individual treatment strategy are prerequisites for survival of acute traumatic aortic lesions. Endovascular stent-graft placement has emerged as an innovative and minimally invasive therapeutic option in this polytraumatic high-risk patient cohort.

Successful type II endoleak closure by subclavian-to-carotid artery transposition after stent-graft placement of a distal aortic arch aneurysm.

Endovascular stent-graft placement has become a safe and effective treatment modality for various diseases of the distal aortic arch as well as of the descending aorta. However, its effectiveness may be limited by various kinds of endoleaks resulting in persistent or recurrent perfusion of the aneurysm sac. Subsequently, systemic pressurization leads to expansion of the aneurysm sac, exposing the patient to a recurrent risk of aneurysm rupture. We report on the case of a 57-year-old male who underwent emergency stent-graft placement in March 2001 due to a contained rupture of a distal aortic arch aneurysm involving the origin of the left subclavian artery. Due to the emergency condition, a subclavian-to-carotid artery transposition had not been performed prior to stent-graft placement. During follow-up the patient developed a type II endoleak originating from the left subclavian artery with consecutive enlargement of the aneurysm sac. The endoleak was successfully treated by subclavian-to-carotid artery transposition.

Cannulation of the axillary artery: the decision between direct cannulation and cannulation via side graft.

BACKGROUND: The axillary artery has emerged as promising alternative cannulation site when the ascending aorta is unsuitable for cannulation. However, in order to minimize vascular injury, the decision to cannulate the artery directly or via graft has to be considered carefully. METHODS: Seventy patients underwent axillary artery cannulation during a two-year period. Indications for operation were acute aortic dissection type A in 25(36 %), ascending aortic or arch aneurysm in 32 (46 %), redo surgery in 6 (9 %), and severely atherosclerotic aorta in 3 (4.3 %) patients. Depending on the diameter of the vessel and the rigidity of the wall, the artery was either cannulated directly or via an 8-mm prosthetic Dacron graft. RESULTS: Direct cannulation was performed in 46 patients (66 %) and cannulation via graft in the remaining 24 patients (34 %). The complication rate associated with axillary artery cannulation was 3.8 %. These two patients developed retrograde type A dissection and further dissection into the descending aorta caused by forceful insertion of a 20-French cannula in a very elastic and small artery. CONCLUSIONS: Cannulation of the axillary artery is an attractive approach with a wide indication spectrum. However, the decision to cannulate directly or via graft should be based on the diameter and elasticity of the vessel, to minimize the complications of vascular injury and subsequent dissection.

Heightened levels of circulating 20S proteasome in critically ill patients.

BACKGROUND: Recently, circulating proteasome core particles (20S proteasome) have been suggested as a marker of cell damage and immunological activity in autoimmune diseases. Aberrant leucocyte activation and increased lymphocyte apoptosis with consecutive T-cell unresponsiveness is deemed to play a pivotal role in the sepsis syndrome. Moreover sepsis-induced muscle proteolysis mainly reflects ubiqutin proteasome-dependent protein degradation. We therefore sought to investigate serum levels of 20S proteasome in critical ill patients. MATERIAL AND METHODS: Case-control-study at a university hospital intensive care unit; 15 patients recruited within 24-48 h of diagnosis of sepsis, 13 trauma patients recruited within 24 h of admission to the ICU, a control group of 15 patients who underwent abdominal surgery, and 15 healthy volunteers. ELISA was used to measure the concentration of 20S proteasome in the sera of the patients and controls. Data are given as mean +/- SEM. Mann-Whitney U-test was used to calculate significance and a P-value of 0.05 was considered to be statistically significant. RESULTS: Marked increase of 20S proteasome was detected in the sera of septic patients (33 551 +/- 10 034 ng mL-1) as well as in trauma patients (29 669 +/- 5750 ng mL-1). In contrast, significantly lower concentrations were found in the abdominal surgery group (4661 +/- 1767 ng mL-1) and in the healthy control population (2157 +/- 273 ng mL-1). CONCLUSION: Detection of 20S proteasome may represent a novel marker of immunological activity and muscle degradation in sepsis and trauma patients, and may be useful in monitoring the clinical effect of proteasome-inhibitors.

Alpha-Gal on bioprostheses: xenograft immune response in cardiac surgery.

BACKGROUND: The alpha-Gal (Galalpha1,3-Galbeta1-4GlcNAc-R) epitope is the major xenoantigen causing hyperacute rejection of pig organs transplanted into primates. Porcine bioprostheses are utilized in cardiac surgery. However, premature degeneration of bioprostheses has limited utilization in younger patients and the immune response remains elusive. We sought to investigate whether a specific alpha-Gal immune response may play a role in this clinical scenario. MATERIALS AND METHODS: We investigated the presence of alpha-Gal-epitope on native and fixed porcine valves by means of confocal laser scanning microscope (CLSM). ELISA was utilized to evidence whether implantation of bioprostheses elicits augmentation of pre-existing cytotoxic anti alpha-Gal IgM antibodies within 10 days of surgery. Patients who underwent coronary artery bypass grafting (CABG) or mechanical valve replacement served as controls (each group, n = 12). To corroborate the clinical relevance of the alpha-Gal immune response in vivo, we studied serum obtained before and after implantation of bioprostheses and its potency to lyse porcine alpha-Gal-bearing PK15 cells. RESULTS: We found the immunogenic alpha-Gal-epitope on fibrocytes interspersed in the connective tissue of porcine valves as determined by vimentin/IB4 lectin binding. Moreover, patients who were provided with a bioprostheses had developed a significant increase of naturally occurring cytotoxic IgM antibodies directed towards alpha-Gal after surgical intervention as compared with control patients (P < 0.0001, respectively). Sera obtained from the patients after the implantation of bioprostheses demonstrated an increased cytotoxicity against alpha-Gal-bearing PK-15 cells as compared with preoperative sera (P < 0.001). The specificity of the cytotoxic effects was proven as soluble Galalpha1-3Galbeta1-4GlcNAc markedly inhibited cell death of alpha-Gal-bearing PK15 cells (P < 0.001). CONCLUSION: Our data suggest that implantation of bioprostheses in cardiac surgery induces a xenograft-specific immune response. Procedures diminishing the presence of alpha-Gal on bioprostheses, such as utilization of genetically manipulated alpha-Gal-deficient xenograft or pretreatment with alpha-Galactosidase, might diminuate the immune response against bioprostheses and extend durability.

Increased serum concentrations of soluble CD95/Fas and caspase 1/ICE in patients with acute angina.

OBJECTIVES: To investigate the expression of death inducing receptors in the sera of patients with stable and unstable angina. DESIGN: 80 consecutive patients with stable (n = 40) or unstable (n = 40) angina pectoris were studied. Serum concentrations of soluble CD95 (sCD95), soluble CD95 ligand (sCD95L; CD178), tumour necrosis factor (TNF) alpha, soluble TNFalpha receptor type 1 (sTNFR1), and interleukin 1beta converting enzyme (ICE; caspase 1) were measured by enzyme linked immunosorbent assay (ELISA). RESULTS: Significant increases in the concentrations of sCD95 and ICE (p < 0.001 and p < 0.023, respectively) were found in the serum from patients with unstable angina relative to those with stable angina. There were no significant differences in the concentrations of sCD95L, TNF alpha, and sTNFR1 between the groups. CONCLUSIONS: These data provide the first evidence that sCD95 and ICE are important serological markers that may help to discriminate between stable and unstable angina. This observation may warrant further clinical study to elucidate the clinical impact of sCD95 and ICE in acute coronary syndromes.

Prognostic value of immunohistochemical expression of p53, bax, Bcl-2 and Bcl-xL in resected non-small-cell lung cancers.

AIMS: Some experimental evidence suggests that in lung cancer, development, progression and an increased proliferation rate can be linked to apoptosis-related factors. In this study we evaluated the possible role of p53 and Bcl-2 gene family members as prognostic factors for non-small-cell lung cancer. METHODS AND RESULTS: We investigated the immunohistochemical expression of p53 and Bcl-2 gene family members (bax, Bcl-2 and Bcl-xL) in 94 non-small-cell lung cancer specimens to establish the role of these genes in lung cancer pathogenesis, and to evaluate their prognostic importance. The expression of Bcl-2 was correlated with a shorter patient survival time and with the nodal status of the neoplasm. We also found frequent over-expression of bax and Bcl-xL to be of no prognostic significance. Finally, we found no correlation between frequent detection of aberrant p53 protein and expression of either Bcl-2, bax or Bcl-xL or with patient survival time. CONCLUSIONS: This study confirms a relevant role for apoptosis-regulatory proteins in the pathogenesis of lung cancer, and highlights the possible role of Bcl-2 as a prognostic factor for this tumour.

Analysis of cell cycle regulator proteins in non-small cell lung cancer.

BACKGROUND/AIMS: Abnormalities of the proteins involved in cell cycle checkpoints are extremely common among almost all neoplasms. This study aimed to investigate the expression of four components of the cell cycle machinery-p21, p16, p53, and proliferating cell nuclear antigen (PCNA)-in non-small cell lung cancer (NSCLC). METHODS: The expression of p21, p16, p53, and PCNA was examined in 68 well characterised NSCLC specimens using immunohistochemistry. The coregulation of these proteins and their influence on survival were analysed using both univariate and multivariate analyses. RESULTS: By univariate analysis, the expression of all the proteins examined, except for PCNA, was significantly correlated with survival. In multivariate analysis, the only immunohistochemical parameter able to influence overall survival was p16, confirming the hypothesis that the RB-p16 tumour suppressor pathway is inactivated in most lung cancer samples. Finally, the group of patients with NSCLC who were negative for both p21 and p16 had a significantly shorter overall survival. CONCLUSIONS: These results suggest that loss of control of cell cycle checkpoints is a common occurrence in lung cancers, and support the idea that functional cooperation between different cell cycle inhibitor proteins constitutes another level of regulation in cell growth control and tumour suppression.