A Modified Calculation Improves the Accuracy of Predicted Postoperative Lung Function Values in Lung Cancer Patients.

PURPOSE: Preoperative pulmonary function testing is mandatory for non-small cell lung cancer (NSCLC) surgery. The predicted postoperative FEV1 (ppoFEV1) is used for further risk stratification. We compared the ppoFEV1 with the postoperative FEV1 (postFEV1) in order to improve the calculation of the ppoFEV1. METHODS: 87 patients voluntarily received an FEV1 assessment 1 year after surgery. ppoFEV1 was calculated according to the Brunelli calculation. Baseline characteristics and surgical procedure were compared in a uni- and multivariate analysis between different accuracy levels of the ppoFEV1. Parameters which remained significant in the multinominal regression analysis were evaluated for a modification of the ppoFEV1 calculation. RESULTS: Independent factors for a more inaccurate ppoFEV1 were preoperative active smoking (odds ratio (OR) 4.1, confidence interval (CI) 3.6-6.41; p = 0.01), packyears (OR 4.1, CI 3.6-6.41; p = 0.008), younger age (OR 1.1, CI 1.01-1.12; p = 0.03), and patients undergoing pneumectomy (OR 5.55, CI 1.35-23.6; p = 0.01). For the customized ppoFEV1 we excluded pneumonectomies. For patients < 60 years, an additional lung segment was added to the calculation. ppoFEV1 = preFEV1 × [Formula: see text]. For actively smoking patients with more than 30 packyears we subtracted one lung segment from the calculation ppoFEV1 = PreFEV1 × [Formula: see text]. CONCLUSION: We were able to enhance the predictability of the ppoFEV1 with modifications. The modified ppoFEV1 (1.828 l ± 0.479 l) closely approximates the postFEV1 of 1.823 l ± 0.476 l, (0.27%) while the original ppoFEV1 calculation is at 1.78 l ± 0.53 (2.19%). However, if patients require pneumectomy, more complex techniques to determine the ppoFEV1 should be included to stratify risk.

Risk Factors Associated with In-Hospital Mortality for Patients with Acute Abdomen After Cardiac Surgery.

OBJECTIVES: Management of acute abdomen (AA) differs due to the heterogeneity of underlying pathophysiology. Complications of AA and its overall outcome after cardiac surgery are known to be associated with poor results. The aim of this retrospective analysis was to evaluate risk factors for AA in patients undergoing cardiac surgery. METHODS: Between December 2011 and December 2014, a total of 131 patients with AA after cardiac surgery were identified and retrospectively analyzed using our institutional database. Statistical analysis of risk factors concerning in-hospital mortality of mentioned patient cohort was performed using IBM SPSS Statistics. RESULTS: Overall in-hospital mortality was 54.2% (71/131). Analyzing in-hospital non-survivors (NS) versus in-hospital survivors (S) peripheral artery disease (28.2% vs. 11.7%; p = 0.03), the need for assist device therapy (33.8% vs. 16.7%; p = 0.03) and the requirement of hemodialysis (67.6% vs. 23.3%; p < 0.01) were significantly higher in NS. Furthermore, lactic acid values at onset of symptoms were shown to be significantly higher in NS (5.7 ± 5.7 mmol/L vs. 2.8 ± 2.9 mmol/L; p < 0.01). Assured diagnosis of mesenterial ischemia was strongly associated with worse outcome (odds ratio 10.800, 95% confidence interval 2.003-58.224; p = 0.006). CONCLUSION: In conclusion, in critically ill patients after performed cardiac surgery peripheral vascular disease, need for supportive hemodynamic assist device systems and occurrence of renal failure are risk factors associated with worsen outcome. Additionally, rise of lactic acid could potentially be associated with onset of intestinal malperfusion and should be taken into account in therapeutic decisions preventing fatal mesenterial ischemia.

Current clinical use of intravenous fosfomycin in ICU patients in two European countries.

PURPOSE: In Europe, intravenous fosfomycin (IV) is used particularly in difficult-to-treat or complex infections, caused by both Gram-positive and Gram-negative pathogens including multidrug-resistant strains. Here, we investigated the efficacy and safety of intravenous fosfomycin under real-life conditions. METHODS: Prospective, multi-center, and non-interventional study in patients with bacterial infections from 20 intensive care units (ICU) in Germany and Austria (NCT01173575). RESULTS: Overall, 209 patients were included (77 females, 132 males, mean age: 59 ± 16 years), 194 of which were treated in intensive care (APACHE II score at the beginning of fosfomycin therapy: 23 ± 8). Main indications (± bacteremia or sepsis) were infections of the CNS (21.5%), community- (CAP) and hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP, 15.3%), bone and joint infections (BJI, 11%), abdominal infections (11%), and bacteremia (10.5%). Most frequently identified pathogens were S. aureus (22.3%), S. epidermidis (14.2%), Enterococcus spp. (10.8%), E. coli (12.3%) and Klebsiella spp. (7.7%). At least one multidrug-resistant (MDR) pathogen was isolated from 51 patients (24.4%). Fosfomycin was administered with an average daily dose of 13.7 ± 3.5 g over 12.4 ± 8.6 days, almost exclusively (99%) in combination with other antibiotics. The overall clinical success was favorable in 81.3% (148/182) of cases, and in 84.8% (39/46) of patients with ≥ 1 MDR pathogen. Noteworthy, 16.3% (34/209) of patients developed at least one, in the majority of cases non-serious, adverse drug reaction during fosfomycin therapy. CONCLUSION: Our data suggest that IV fosfomycin is an effective and safe combination partner for the treatment of a broad spectrum of severe bacterial infections in critically ill patients.

Risk factors associated with 30-day mortality for out-of-center ECMO support: experience from the newly launched ECMO retrieval service.

Out-of-hospital extracorporeal membrane oxygenation (ECMO) implantation and ECMO transport have become a growing field useful for emergent treatment of heart or lung failure with increasing number of centers launching such service. This study was designed to present risk factors predicting 30-day mortality for patients receiving ECMO support in a newly launched ECMO retrieval service. From 01/2015 till 01/2017 28 consecutive patients received ECMO support in peripheral hospitals using a miniaturized portable Cardiohelp System® (Maquet, Rastatt Germany) for heart, lung or heart/lung failure as a bridge-to-decision as a part of our newly launched ECMO retrieval service. Outcomes and predictors for 30-day mortality were presented. The mean age was 56 ± 15 (maximum 78) years. The mean ECMO support duration was 97 ± 100 h, whereas 11 patients (40%) were weaned off support and discharged from hospital. Presence of hemolysis (p = 0.041), renal failure (p = 0.016), lower platelet count before ECMO implantation (p = 0.001), and higher lactate 24 h after initiation of support (p = 0.006) were factors associated with 30-day mortality. Initial success of an ECMO retrieval service depends on logistic organization and clinical management. Taking into consideration highly deleterious effects of hemodynamic malperfusion of end organs, rapid initiation of ECMO support is a vital factor for survival. This is highlighted by predictive factors of early mortality that are associated with peripheral organ failure or complications.

[Surgical treatment of aortic valve stenosis]. / Chirurgische Therapie der Aortenklappenstenose.

Surgical aortic valve replacement still represents the gold standard in patients with severe symptomatic aortic valve stenosis. In addition to conventional aortic valve replacement by mechanical or biological prostheses via a median sternotomy, novel approaches including minimally invasive strategies and new devices, such as so-called rapid deployment prostheses, are becoming increasingly more established. Autologous replacement strategies including the Ross and the Ozaki procedures have evolved into reliable options at selected centers of excellence. These novel treatment approaches in aortic valve surgery result in excellent short and long-term outcomes with a reduction of procedure-related complications. Taken together, these modern surgical replacement strategies enable a personalized surgical treatment in patients with aortic valve stenosis, which are tailored to the individual patient.

[Role of Laser Resection in Pulmonary Metastasectomy]. / Die Rolle der Laserresektion in der Lungenmetastasenchirurgie.

Objectives This review presents laser resection as treatment option in pulmonary metastasectomy and summarizes the current evidence. Moreover, it includes the comparison of laser resection and common techniques used in lung metastasectomy. Methods We performed a systematic literature research in Medline and the Cochrane library to detect case series and even randomized trials. All included studies underwent qualitative analysis. Results Laser metastasectomy is a safe procedure. Data regarding relevant clinical end points as hospitalization, duration of chest tube drainage and long-term survival are heterogeneous and still controversial. Laser enucleation decreases the resection volume. Therefore, it leads to a significant reduction of parenchymal loss. Survival rates after laser metastasectomy are equal to the outcome after resection using other techniques. Conclusions Laser resection is a parenchyma-sparing method. Hence, it offers radical metastasectomy even in case of multiple pulmonary lesions or impaired lung capacity.

Leiomyosarcoma of the inferior vena cava extending into the right atrium. A rare differential diagnosis of a right atrial tumor with fatal outcome.

A 54-year-old female patient presented with a progressive and deteriorating dyspnea at the slightest exertion in particular during the past few days before presentation. Transthoracic echocardiography revealed a large space-occupying lesion in the right atrium extending into the inferior vena cava (IVC). Abdominal magnetic resonance aortography showed an elongated space-occupying lesion in the IVC with a significant portion of the tumor and almost completely filling the right atrium accompanied by an infiltration of the hepatic and renal veins. A pronounced tumor infiltration of the IVC at the level of the liver was confirmed intraoperatively and immunohistochemical analysis showed a moderate to poorly differentiated leiomyosarcoma. The extended tumor was successfully removed by a complex operation of the thorax and abdomen but the procedure was accompanied by severe bleeding. A few hours following the procedure the patient died due to a further episode of irreversible intra-abdominal hemorrhage.

State of the art in neuroprotection during acute type A aortic dissection repair.

Temporary (TND) or permanent neurologic dysfunctions (PND) represent the main neurological complications following acute aortic dissection repair. The aim of our experimental and clinical research was the improvement and update of the most common neuroprotective strategies which are in present use. HYPOTHERMIC CIRCULATORY ARREST (HCA): Cerebral metabolic suppression at the clinically most used temperatures (18-22°C) is less complete than had been assumed previously. If used as a 'stand-alone' neuroprotective strategy, cooling to 15-20°C with a jugular SO(2) ≥ 95% is needed to provide sufficient metabolic suppression. Regardless of the depth of cooling, the HCA interval should not exceed 25 min. After 40 min of HCA, the incidence of TND and PND increases, after 60 min, the mortality rate increases. ANTEGRADE SELECTIVE CEREBRAL PERFUSION (ASCP): At moderate hypothermia (25-28°C), ASCP should be performed at a pump flow rate of 10ml/kg/min, targeting a cerebral perfusion pressure of 50-60mmHg. Experimental data revealed that these conditions offer an optimal regional blood flow in the cortex (80±27ml/min/100g), the cerebellum (77±32ml/min/100g), the pons (89±5ml/min/100g) and the hippocampus (55±16ml/min/100g) for 25 minutes. If prolonged, does ASCP at 32°C provide the same neuroprotective effect? CANNULATION STRATEGY: Direct axillary artery cannulation ensures the advantage of performing both systemic cooling and ASCP through the same cannula, preventing additional manipulation with the attendant embolic risk. An additional cannulation of the left carotid artery ensures a bi-hemispheric perfusion, with a neurologic outcome of only 6% TND and 1% PND. NEUROMONITORING: Near-infrared spectroscopy and evoked potentials may prove the effectiveness of the neuroprotective strategy used, especially if the trend goes to less radical cooling. CONCLUSION: A short interval of HCA (5 min) followed by a more extended period of ASCP (25 min) at moderate hypothermia (28°C), with a pump flow rate of 10ml/kg/min and a cerebral perfusion pressure of 50 mmHg, represents safe conditions for open arch surgery.

Impact of urgent coronary artery bypass grafting on acute kidney injury : A matched cohort study.

OBJECTIVES: There is limited knowledge regarding the specific interrelationships between urgent coronary artery bypass graft (U-CABG) surgery and postoperative acute kidney injury (AKI). We aimed to (1) analyze the impact of urgent CABG (U-CABG) on the incidence and severity of postoperative AKI, (2) estimate the influence of AKI after U­CABG or elective CABG (E-CABG) on mortality and (3) identify risk factors for AKI depending on the urgency of operation. RESULTS: U­CABG patients showed a higher incidence of AKI (49.8% vs. E­CABG: 39.7%; p = 0.026), especially for higher AKI stages 2 + 3. In-hospital mortality was higher in U­CABG patients (12.6%) compared to E­CABG patients (2.3%; p < 0.001). The impact of AKI on mortality did not differ, but showed a strong coherency between higher AKI stages (2 + 3) and mortality (stage 1: OR 2.409, 95% CI 1.017-5.706; p = 0.046 vs. stage 2 + 3: OR 5.577; 95% CI 2.033-15.3; p = 0.001). Univariate logistic regression analysis revealed that preoperative renal impairment, peripheral vascular disease and transfusion of more than two red blood cell concentrates were predictors for postoperative AKI in both groups. CONCLUSIONS: U­CABG is a risk factor for postoperative AKI and even "mild" AKI leads to a significantly higher mortality. Hence, the prevention of modifiable risk factors might reduce the incidence of postoperative AKI and thus improve outcome.

The acute effect of IABP-induced pulsatility on coronary vascular resistance and graft flow in critical ill patients during ECMO.

AIM: The combination of the two cardiac support mechanisms of intra-aortic balloon pumping (IABP) and non-pulsatile circulatory extracorporeal membrane oxygenation (ECMO) has been confirmed to improve efficacy of the cardiac support as a whole. However, reports on benefits of diastolic augmentation on coronary vascular bed and graft flowmetry during concomitant use of IABP and ECMO are lacking. The aim of this study was to evaluate the acute impact of IABP support on coronary vascular resistance (CVR) and coronary bypass flows (CBF) in high-risk patients with peripheral ECMO following coronary artery bypass grafting (CABG). METHODS: In eight emergency CABG patients (mean age=67.8±1.9 years; gender: six male and two female; EF=25.5±2.4%) requiring mechanical circulatory support with ECMO hemodynamic parameters, CVR, CBF, diastolic filling index (DFI), graft flow reserve (GFR), and pulsatility index (PI) were analyzed with and without diastolic augmentation using a transit time flowmeter. RESULTS: The addition of IABP to ECMO decreased CVR significantly by 6.5%±1.9% compared to baseline with ECMO alone (1.62±0.2 versus 1.78±0.2; P<0.0045). Accordingly, significant higher mean CBF were found during IABP assist, resulting in a 21.6%±2.6% increase (60.7±8.7 mL/min with versus 51.3±7.4 mL/min without IABP; P<0.0001). IABP also significantly increased DFI by 9.8±0.9% (73.2%±1.4% with versus 66.7%±1.3% without IABP; P<0.0001). GFR was recruited during IABP in all grafts (GFR>1). There were no statistically significant differences in PI with and without IABP assistance (2.6±0.1 versus 2.5±0.2). CONCLUSION: IABP-induced pulsatility significantly improves diastolic filling index and mean coronary bypass graft flows by lowering coronary vascular resistance during non-pulsatile peripheral ECMO. The combination of ECMO with IABP may provide more optimal myocardial oxygen conditions resulting in an improved efficacy of the cardiac support as a whole in critical ill patients with postcardiotomy myocardial dysfunction following CABG.

Myocardial protection in cardiac surgery patients requiring prolonged aortic cross-clamp times: a single-center evaluation of clinical outcomes comparing two blood cardioplegic strategies.

AIM: The aim of this study was to evaluate the impact of intermittent warm (IWC) versus intermittent cold blood cardioplegia (ICC) in high-risk patients that require prolonged periods of aortic cross-clamping during on-pump cardiac surgery. METHODS: From 3527 consecutive patients undergoing on-pump cardiac surgery, 520 patients were retrospectively identified that required prolonged aortic cross-clamp ≥ 75 min. Myocardial protection was performed with ICC (N.=280) or IWC (N.=240). Groups were compared regarding clinical outcomes, myocardial injury (CK-MB, cTnT) and multivariate analysis was performed to assess the impact of applied cardioplegia on 30-day all-cause mortality, cardiac death, perioperative myocardial injury (PM) and major adverse cardiac events (MACE). RESULTS: Demographic data, mean logistic Euroscore, aortic-cross-clamping and CPB time were comparable between groups. Patients with ICC needed more intraoperative defibrillations, had more postoperative blood transfusions and a prolonged hospital stay when compared to the IWC-group (P < 0.05). Thirty-day all-cause mortality tended to be higher in IWC (11% vs. 6%; P = 0.083) with significantly higher cardiac mortality (9% vs. 4%; P=0.015) compared to ICC. Myocardial injury was more pronounced in the IWC-group with a higher incidence of PMI (IWC: 17% vs. ICC:6%; P < 0.05) and MACE (IWC:37% vs. ICC:25%; P < 0.05). Groups did not differ regarding other postoperative clinical outcomes. Multivariate analysis revealed IWC to be independently predictive (P < 0.05) for 30-day all-cause mortality (OR:2.42; 95% CI:1.04-5.05), cardiac death (OR:3.57; 95% CI:1.49-8.85), MACE (OR:1.87; 95% CI:1.22-2.87) and PMI (OR:3.46; 95% CI:1.86-6.41). CONCLUSION: ICC results in less myocardial damage and reduced postoperative cardiac mortality and morbidity in patients requiring extended periods of aortic-cross-clamping during on-pump cardiac surgery, suggesting superior cardioprotection when compared to IWC.

Pre-ischaemic exogenous surfactant reduces pulmonary injury in rat ischaemia/reperfusion.

The optimal timing of exogenous surfactant application to reduce pulmonary injury and dysfunction was investigated in a rat lung ischaemia and reperfusion injury model. Lungs were subjected to flush perfusion, surfactant instillation, cold ischaemia (4 degrees C, 4 h) and reperfusion (60 min). Animals received surfactant before (group 1) or at the end (2) of ischaemia, or during reperfusion (3) or not at all (4). Control groups included "worst case" without Perfadex and surfactant (5), "no injury" without (6) or with surfactant (7), and ischaemia with pre-ischaemic surfactant (8). Intra-alveolar oedema and blood-air barrier injury were estimated by light and electron microscopic stereology. Perfusate oxygenation and pulmonary arterial pressure (P(pa)) were determined during reperfusion in groups 1 to 4. Intra-alveolar oedema was almost absent in groups 1, 6, 7 and 8, pronounced in 2, 3 and 4, and severe in 5. Blood-air barrier injury was moderate in groups 1 and 8, slightly pronounced in 2, 3 and 4, extensive in 5 and almost absent in 6 and 7. Perfusate oxygenation was significantly higher in group 1 compared with groups 2 to 4. P(pa) did not differ between the groups. In conclusion, exogenous surfactant attenuates intra-alveolar oedema formation and blood-air barrier damage and improves perfusate oxygenation in the rat lung, especially when applied before ischaemic storage.

Preliminary results of small arterial substitute performed with a new cylindrical biomaterial composed of bacterial cellulose.

OBJECTIVE: Tissue-engineered blood vessels (TEBVs) represent an innovative approach for overcoming reconstructive problems associated with extended vascular diseases by providing small-calibre vascular grafts. This study aimed to evaluate a novel biomaterial of bacterially synthesised cellulose (BC) as a potential scaffold for TEBV. METHODS: Highly crystalline cellulose was produced by a bacterium (Acetobacter xylinum) using glucose as a source of carbon. Using a patented process, hollow-shaped segments of BC were created with a length of 10mm, an inner diameter of 3.0-3.7mm and a wall thickness of 0.6-1.0mm. These grafts were used to replace the carotid arteries of eight pigs, and after a follow-up period of 3 months, the grafts were removed and analysed, both macro- and microscopically. RESULTS: Seven grafts (87.5%) remained patent, whereas one graft was found to be occluded. Scanning electron microscopic examination revealed rapid re-cellularisation by recipient endothelial cells. Light microscopic examination showed a three-layered wall structure of the BC segments, with cellulose still being present in the media. CONCLUSION: These data indicate that the innovative BC-engineering technique results in the production of stable vascular conduits, which exhibit attractive properties for their use in future TEBV programmes for vascular surgery.

Inhibition of the alpha1beta1 isoform of the Na, K-ATPase by 8-methoxycoumestrol without positive inotropic effect in human myocardium--novel aspects of cardiac glycoside pharmacology.

BACKGROUND: The Na,K-ATPase (NKA) is necessary for maintaining the resting membrane potential by transporting Na and K ions across the cell membrane. Although its 3 isoforms expressed in human heart (alpha1beta1, alpha2beta1, and alpha3beta1) possess similar biochemical properties, their specific functions in human tissues remain unknown. In our search for an isoform-specific agent, which can serve to identify isoform-specific functions, we examined 8-methoxycoumestrol in its ability to inhibit the NKA and to produce inotropism in connection with the possibility to identify the NKA isoform-specific functions. METHODS AND RESULTS: In radioligand binding experiments (membrane preparations of yeast expressing isoforms alpha1beta1, alpha2beta1, and alpha3beta1; backdoor phosphorylation; and [H]-ouabain, n = 3), 8-methoxycoumestrol (1-10 microM) produced no or only little inhibition of specific ouabain binding. However, when NKA activity of the alpha1beta1 isoform was measured in membrane preparations from human kidney (reduced form of nicotinamide adenine dinucleotide-coupled assay, n = 3), a concentration-dependent full inhibition of the activity was induced by 8-methoxycoumestrol (IC50: 90 +/- 97 nM), similar to that observed for classical cardiac glycosides digitoxin, digoxin, methyldigoxin, and beta-acetyldigoxin (IC50 = 287 +/- 190 nM, 409 +/- 171 nM, 282 +/- 482 nM, 587 +/- 135 nM, P > 0.05). However, unlike the classical cardiac glycosides, 8-methoxycoumestrol did not increase cardiac contractility of electrically stimulated human right atrial trabeculae. CONCLUSIONS: These results indicate that 8-methoxycoumestrol inhibits the human alpha1beta1 NKA by a mechanism different to that of cardiac glycosides. In addition, the inhibition of the alpha1beta1 NKA activity seems not sufficient to evoke positive inotropy in human trabeculae, indicating that either the positive inotropic effect of cardiac glycosides is not mediated via the alpha1beta1 isoform or the specific glycoside binding to alpha1beta1 is needed for positive inotropy.

[Pulmonary metastasectomy in renal cell carcinoma]. / Lungenmetastasenchirurgie beim Nierenzellkarzinom.

BACKGROUND: In patients with isolated meta- or synchronous pulmonary metastases from renal cell cancer, lung metastasectomy could be an appropriate treatment option after successful treatment of primary cancer. OBJECTIVES: Presentation of lung metastasectomy as a treatment option in patients with pulmonary metastatic renal cell cancer and the postoperative outcome. Description of alternative treatment modalities focusing on "targeted therapies". MATERIALS AND METHODS: Systematical literature research and qualitative analysis of studies on patients undergoing lung metastasectomy after primary nephrectomy published since 01 January 2000. We assessed operative findings, survival data, and prognostic factors. RESULTS: Pulmonary metastasectomy results in a median postmetastasectomy survival of 26-94 months. The 5­year survival rates vary between 33 and 58%. The patients' prognosis depends on a prolonged disease-free interval and complete resection of all suspected metastases. In particular, number and location of lung metastases should play a minor role for the indication for lung metastasectomy. CONCLUSIONS: Pulmonary metastasectomy should be considered the treatment of choice in selected patients with successfully resected primary cancer showing no evidence of extrapulmonary metastases and having guaranteed operability and complete resection.

Transcriptomic and proteomic patterns of systemic inflammation in on-pump and off-pump coronary artery bypass grafting.

BACKGROUND: Coronary artery bypass grafting (CABG) using cardiopulmonary bypass (CPB) provides controlled operative conditions but induces a whole-body inflammatory response capable of initiating devastating morbidity and mortality. Although technically more demanding, deliberate avoidance of CPB in off-pump surgery attenuates the physiological insult associated with CABG. METHODS AND RESULTS: To systematically assess the molecular mechanisms underlying the better-preserved remote organ function, we studied gene expression patterns in leukocytes and plasma proteomic response to on-pump and off-pump CABG. Proteomic analysis confirmed (tumor necrosis factor-alpha, interleukin [IL]-6, IL-10) and expanded (eg, interferon [IFN]-gamma, granulocyte colony-stimulating factor [G-CSF], monocyte chemotactic protein-1, macrophage inflammatory protein-1beta) the mediators released on CPB, whereas blood leukocyte transcriptomics suggested that circulating leukocytes are not primarily responsible for this response. Interestingly, release of some cytokines (eg, IL-6, IFN-gamma, G-CSF) was observed on off-pump surgery to a similar extent but with delayed kinetics. A total of 45 of 4868 transcripts were identified to be significantly altered as a result of initiation of CPB. Systematic analysis of transcriptional activation by CPB revealed primarily genes involved in inflammation-related cell-cell communication (such as L-selectin or intercellular adhesion molecule-2) and signaling (such as IL-1, IL-8, or IL-18 receptors and toll-like receptors 4, 5, and 6), thus confirming a "primed" phenotype of circulating peripheral blood mononuclear cells. CONCLUSIONS: Gene array and multiplex protein analysis, only in concert, can illuminate the molecular mechanisms responsible for systemic sequelae of CPB and indicate that circulating leukocytes overexpress adhesion and signaling factors after contact with CPB, which potentially facilitates their trapping, eg, in the lungs and may promote a subsequent tissue-associated inflammatory response.

A classification of cardiac allograft rejection. A modification of the classification by Billingham.

We herein propose a classification of rejection in cardiac allografts based on the original Stanford work. Our modified classification, as a work hypothesis, defines the following grades: mild acute rejection (A-1), corresponding to Billingham's "mild rejection"; mild acute rejection with probable conversion to moderate rejection (A-2); moderate acute rejection (A-3), comparable to Billingham's "moderate rejection"; and severe acute rejection (A-4), morphologically identical with the respective grade in the Billingham classification. The resolution of rejection has been classified into two grades--early (A-5a) and late (A-5b) resolution--according to the development of granulation tissues. We also grade the degree of vasculopathy (B-1, B-2) and chronic rejection (C), which is characterized by aggressive fibrosis and persistent vasculopathy. Mild rejection with possible conversion to moderate rejection is defined by an increasing quantity of retrogressive changes in myocytes. Changes not related to transplantation are characterized in our classification by descriptive diagnosis. The proposed classification was validated by 1 year of clinical experience and by the evaluation of possible prognostic aspects of the classification.

Impact of chronic infection with chlamydia pneumoniae on incidence of cardiac allograft vasculopathy.

Chronic infection with Chlamydia pneumoniae (CP) is associated with development of coronary disease. However, little information exists concerning CP infection and impact on posttransplant cardiac allograft vasculopathy (CAV). A total of 202 patients were investigated 5.5+/-3.1 years after cardiac transplantation (46.5+/-11.0 years; 169 male, 33 female). Assessment of CAV was performed by annual coronary angiograms. Chlamydia serology (IgG/IgA) was performed using micro-immunofluorescence. Statistics comprised analysis of variance and Kaplan-Meier analysis. A total of 152 patients were CAV positive. Elevated titers were present in 45% (IgG) and 72.8% (IgA) of patients. Generally, serostatus was not associated with development of CAV when evaluated over the total postoperative interval. However, after month 14 there was a significant trend toward lower actuarial freedom from CAV in patients with elevated IgA titers. CP seems not to play a significant role in the development of CAV early after heart transplantation but might be a predicting risk factor after the first postoperative year.

Development, stability, and clinical correlations of allogeneic microchimerism after solid organ transplantation.

To assess the development, stability, and clinical relevance of donor-type microchimerism, skin and blood were analyzed in heart (n = 53) and liver (n = 18) transplant recipients by nested polymerase chain reaction. Microchimerism was detectable in 40 (75%) and 13 (72%) patients after heart and liver transplantation, respectively. In heart transplantation, chimerism-positive patients showed a lower frequency of acute rejection as compared with negative patients, although this was only of borderline statistical significance. Repeated intraindividual analyses demonstrated variable patterns of microchimerism over time, but changes did not correlate to the clinical state. In liver transplantation, chimeric state showed no clear correlation with the patients' immunological situation. Our results demonstrate that peripheral microchimerism frequently develops after different types of organ transplantation and represents a dynamic process but without diagnostic value to predict the immunological risk for individual patients.

Impact of plaque burden on compensatory enlargement of coronary arteries in cardiac allograft vasculopathy. Working Group on Cardiac Allograft Vasculopathy.

Using intravascular ultrasound, we demonstrated plaque-induced compensatory enlargement of coronary arteries in cardiac allograft vasculopathy. Besides intimal hyperplasia, adaptive remodeling processes of vessel and luminal geometry have physiologic and prognostic importance.