Prevention of sternal dehiscence and infection in high-risk patients: a prospective randomized multicenter trial.

BACKGROUND: One factor for the development of sternal wound infection (SWI) is bony instability after sternotomy. This study compares two surgical techniques with respect to the occurrence of SWI in patients with an increased risk. METHODS: In this multicenter study, 815 consecutive patients with an increased risk for SWI were prospectively randomly assigned to a conventional osteosynthesis (transsternal or peristernal wiring; n = 440) or to an osteosynthesis with additional lateral reinforcement (Robicsek; n = 375). Primary endpoints were the rate of sternal dehiscence as well as the occurrence of superficial sternal wound infections and deep sternal wound infections. RESULTS: Both groups were comparable concerning preoperative and intraoperative variables. The rate of sternal dehiscence, superficial sternal wound infections, and deep sternal wound infections (conventional technique 2.5%, 3.4%, 2.5%; and Robicsek 3.7%, 5.6%, 3.7%) did not differ between the groups. Logistic regression analysis found independent risk factors for the development of sternal dehiscence: body mass indes greater than 30 kg/m(2) (odds ratio [OR]: 2.9; p = 0.05), New York Heart Association class more than III (OR: 2.4; p = 0.07), impaired renal function (OR: 3.9; p = 0.01), peripheral arterial disease (OR: 3.6; p = 0.001), immunosuppressant state (OR: 3.3; p = 0.001), sternal closure performed by an assistant doctor (OR: 2.5, p = 0.004), postoperative bleeding (OR: 4.2; p = 0.03), transfusion of more than 5 red blood units (OR: 3.7, p = 0.01), reexploration for bleeding (OR: 6.9, p = 0.001), and postoperative delirium (OR: 3.5, p = 0.01). There was an inverse relation between the numbers of wires and DSWI in patients with conventional sternal closure (p = 0.008). CONCLUSIONS: In patients with an increased risk for sternal instability and wound infection after cardiac surgery, sternal reinforcement according to the technique described by Robicsek did not reduce this complication.

Heterotopic rat heart transplantation (Lewis to F344): early ICAM-1 expression after 8 hours of cold ischemia.

BACKGROUND: Primary graft dysfunction is a still poorly understood complication after cardiac transplantation. Ischemia/reperfusion injury contributes to different disorders resulting in impaired graft function. METHODS: In a heterotopic rat heart transplantation model we extended graft ischemic time up to 8 hours. RESULTS: Using immunohistochemistry we detected an up to 4-fold increase in intracellular adhesion molecule-1 (ICAM-1) expression during 4 hours of reperfusion, independent of ischemic time (30-minute ischemia: 7.65 +/- 2.15 without reperfusion, 19.46 +/- 4.6 after 4-hour reperfusion; 240-minute ischemia: 5.6 +/- 1.99 and 22.3 +/- 3.77; 480-minute ischemia: 3.7 +/- 1.56 and 13.1 +/- 2.2). Eight-hour ischemic allografts had an increase in CD8-positive cells (1.37 +/- 0.5 and 2.3 +/- 0.77) and a significant increase in MHC II expression (11.48 +/- 2.1 and 18.27 +/- 1.34) during 4 hours of reperfusion. CONCLUSIONS: We hypothesize that these findings reflect an early inflammatory reaction in the allograft possibly triggered by oxidative stress. During therapeutic interventions, both of these pathways must be considered.

The effectiveness of a motivation programme for lifestyle change in the course of aortocoronary bypass graft surgery.

OBJECTIVE: To evaluate the effectiveness of a motivation programme the motivation for lifestyle change in patients was measured before and after coronary artery bypass graft (CABG) surgery by comparing a usual care group with a group attending a motivation programme. DESIGN: Prospective controlled study. SETTING: University hospital cardiothoracic surgery department. SUBJECTS: One hundred and forty patients (mean age 64.9; SD 8.5 years) who had an elective CABG surgery. INTERVENTIONS: Each patient was evaluated regarding his or her motivation for lifestyle change two days before and 10 days after CABG surgery. Between January and May 2002 patients in usual care were investigated as a control group (n=70). From January to May 2003 patients had the opportunity to take part in a motivation programme that was provided by a trained clinical psychologist (n = 70). The programme consists of both personalized single sessions and group lectures. MEASURES: A 30-item questionnaire measuring the six factors Vulnerability, Intention, Social expectation, Outcome expectation, Self-efficacy expectation, and Perceived severity was developed. RESULTS: ANOVA procedures with repeated measurements indicate significant effects in terms of higher motivation for lifestyle change in the treatment group in Vulnerability (F(1, 138) = 4.04; P=0.04), Intention (F(1, 138) = 19.81; P<0.001), Social expectation (F(1, 138)=21.97; P<0.001), Outcome expectation (F(1, 138) =17.95; P<0.001), and Self-efficacy expectation (F(1, 138) =14.31; P<0.001). CONCLUSIONS: This motivation programme performed in a cardiac surgery hospital after CABG may increase the motivation for a positive lifestyle change.

Presence of depression and anxiety before and after coronary artery bypass graft surgery and their relationship to age.

BACKGROUND: Scientific literature on depression and anxiety in patients with coronary heart disease (CHD) consistently reports data of elevated anxiety and depression scores indicating clinically relevant quantities of these psychopathological conditions. Depression is considered to be a risk factor for the development of CHD and deteriorates the outcome after cardiac rehabilitation efforts. The aim of our study was to evaluate the presence of clinically relevant anxiety and depression in patients before and after coronary artery bypass grafting (CABG). Additionally we evaluated their relationship to age because of the increasing number of elderly patients undergoing CABG surgery. METHODS: One hundred and forty-two consecutive patients who underwent CABG in our hospital were asked to fill in the "Hospital Anxiety and Depression Scale - German Version (HADS)" to measure depression and anxiety scores two days before and ten days after CABG surgery. Differences between these pre- and post-surgical scores were then calculated as means for changes, and the amount of elevated scores were appraised. In order to investigate the relationship between age and anxiety and depression, respectively, Spearman correlations between age and the difference scores were calculated. In addition, ANOVA procedures with the factor "age group" and McNemar tests were calculated. Therefore the sample was divided into four equally sized age groups. RESULTS: 25.8% of the patients were clinically depressed before and 17.5% after surgery; 34.0% of the patients were clinically anxious before and 24.7% after surgery. This overall change is not significant. We found a significant negative correlation between age and the difference between the two time points for anxiety (Spearman rho = -.218; p = 0.03), but not for depression (Spearman rho = -.128; p = 0.21). ANOVA and McNemar-Tests revealed that anxiety scores and the number of patients high in anxiety declined statistically meaningful only in the youngest patient group. Such a relationship could not be found for depression. CONCLUSION: Our data show a relationship between age and anxiety. Younger patients are more anxious before CABG surgery than older ones and show a decline in symptoms while elderly patients show hardly any change.

A clinical chameleon: postoperative hypoparathyroidism.

BACKGROUND: About 1,200 patients per year develop postoperative hypoparathyroidism alone in Germany. Many of those patients may be misdiagnosed as the symptoms of this disease may vary and can be atypical. PATIENT/RESULTS: As an example, we describe the first known case of an elderly patient with a long history of seizures as a complication of an undiagnosed chronic hypoparathyroidism after surgery of a pT4-esophageal carcinoma. The 63-year-old male patient underwent laryngo-hypopharyngo-esophagectomy with gastric transposition and partial thyroid resection for a proximal esophageal carcinoma in 1994. About half a year later, the patient developed for the first time a convulsive syncope. Misleading diagnoses were for years suspected metastasis formation and a dumping syndrome. The general physician of the patient called him the epilepsy man, while no cause of the seizures were found. More than a decade of years later, when the correct diagnosis was made, finally by determination of parathyroid hormone levels, the seizures of the patient were completely eliminated by calcium supplementation therapy. The patient's quality of life improved clearly in the following time. CONCLUSION: It is essential to consider chronic hypoparathyroidism in the differential diagnosis of patients with hypocalcemia who have undergone extended neck and proximal esophageal surgery before. In addition to that, it is mandatory to autotransplant parathyroids during the initial procedure which might be accidentally removed during surgery and to monitor parathyroid function in each patient in the further course postoperatively.

Cardiac allograft vasculopathy after cardiac transplantation and hormone therapy: positive effects?

BACKGROUND: There is a great deal of controversy surrounding the issue of hormone replacement therapy after transplantation. The question whether or not this therapy has effects in cardiac allograft vasculopathy (CAV), the Achilles heel of cardiac transplantation or other unique aspects of allograft function is still unknown. METHODS: We investigated the long-term effect of 17beta-estradiol as well as phytoestrogen Coumestrol, a synthetically produced phytoestrogen, on the development of CAV and the degree of fibrosis in an ovariectomized female heterotopic chronic allograft model (LEW-F344). RESULTS: We found that, 150 days after transplantation, no significant effect of estrogen application on intimal thickening of coronary arteries was observed. 17beta-estradiol and phytoestrogen Coumestrol did significantly reduce the perivascular immune reaction. However, the immune effect had no consequence on the intensity of CAV. Although neither 17beta-estradiol nor phytoestrogen Coumestrol revealed a positive effect on CAV, the group of animals treated with 17beta-estradiol showed the highest decline in heart function and the most distinct fibrosis. CONCLUSIONS: 17beta-estradiol does not affect CAV positively, but worsens cardiac allograft function and leads to increased fibrosis. This is the first study showing a negative effect of 17-beta-estradiol after heart transplantation in the long term.

Left ventricular non-compaction associated with a genetic variant of the CYP2C9 gene.

Polymorphisms in the CYP2C9 gene can have a significant impact on drug therapy by affecting the pharmacokinetics of frequently prescribed drugs, such as phenprocoumon and warfarin. It is essential therefore that genetic CYP2C9 variants are excluded in patients with a suspected intolerance of anticoagulant therapy. Here we present the first report of a case of left ventricular non-compaction syndrome associated with a genetic variant of the CYP2C9 gene in a 45-year-old woman with myocardial insufficiency who was scheduled for implantation of a cardioverter defibrillator.

Staging of non-small cell lung cancer: clinical value of positron emission tomography and mediastinoscopy.

We report about a MEDLINE research from 2000 to 2005 with the key words 'positron emission tomography AND/OR mediastinoscopy'. The search identified 448 potential studies. Out of the published data sensitivity, specificity, positive and negative predictive value, and accuracy for mediastinal lymph node staging by FDG-PET ranged from 58%-94%, 76%-96%, 43%-95%, 56%-98% to 74%-91%, respectively. With corresponding values of 80%-96%, 100%, 100%, 92%-97%, and 94%, respectively, for mediastinoscopy. FDG-PET improved the rate of detection of local and distant metastases in 12% to 62% and changed the management of treatment in 8% to 60% of patients with NSCLC. Our study shows that in the diagnostic strategy of patients with NSCLC, additional FDG-PET can prevent non-therapeutic thoracotomy in a significant number of cases. If FDG-PET imaging and CT scan is negative for mediastinal lymph node involvement routinely mediastinoscopy can be omitted and thoracotomy can immediately be performed. In patients with negative FDG-PET scan, but positive CT scan, histologic verification by invasive methods can individually be considered. Patients with positive FDG-PET scan mediastinoscopy still remain a reliable standard for exact lymph node staging. By incorporating FDG-PET in clinical staging unnecessary exploratory thoracotomies, and mediastinoscopy, can be omitted.

Formation of 4-hydroxy-2-nonenal protein adducts in the ischemic rat heart after transplantation.

BACKGROUND: Free radicals formed during ischemia and reperfusion can lead to lipid peroxidation (LPO) and the formation of 4-hydroxy-2-nonenal (4-HNE), one of the most toxic products of LPO. Using a heterotopic rat heart transplantation model we investigated endogenous 4-HNE formation as a response to cold storage of the transplant and warm blood reperfusion in the recipient. METHODS: Lewis rat hearts were subjected to 30, 240 or 480 minutes of 4 degrees C cold ischemia in Bretschneider cardioplegic solution without or with transplantation and 240-minute reperfusion in F344 recipients. The amount of 4-HNE modified proteins was quantified in rat heart cryosections with an antibody recognizing cysteine-, histidine- and lysine-4-HNE Michael adducts and image analysis of immunostained tissue. RESULTS: We detected 4-HNE-modified proteins in ischemic rat hearts after transplantation and reperfusion. In hearts submitted to ischemia only, 4-HNE-protein adducts comprised 0.7 +/- 0.3% (30 minutes), 0.7 +/- 0.4% (240 minutes) and 0.2 +/- 0.1% (480 minutes) (mean +/- SEM) of the tissue area. Transplantation and reperfusion in the recipient significantly increased the amount of protein adducts to 6.8 +/- 2.6% (p = 0.041), 5.2 +/- 1.4% (p = 0.009) and 5.7 +/- 0.9% (p = 0.002) in 30-, 240- and 480-minute ischemic hearts, respectively. CONCLUSIONS: Under the conditions applied in the present study, cold ischemia for >30 minutes did not significantly alter the amount of 4-HNE protein adducts. However, because after transplantation and reperfusion, 6% of heart tissue consisted of 4-HNE-modified proteins, it can be assumed that this damage negatively affects long-term survival of the transplant.

Selective loss of regulatory T cells in thymomas.

Myasthenia gravis (MG) is the prime autoimmune manifestation of thymomas. We investigated the generation of T cells with a regulatory phenotype (T(R)) in thymomas with and without associated MG. In patients with MG(+) thymomas, maturation and export of T(R) cells but not of other T-cell subsets was significantly reduced. We conclude that imbalance between effector and regulatory T cells in thymomas may be involved in modulation of onset and/or severity of MG.

Heterotopic rat heart transplantation: severe loss of glutathione in 8-hour ischemic hearts.

BACKGROUND: Tissue damage caused by reactive oxygen species (ROS) formed during ischemia/reperfusion seems to be an important risk factor in the failure of transplanted hearts. Although endogenous anti-oxidants protect the myocardium against free radical attack under physiologic conditions, their capacity may become limited during severe oxidative stress. Thus, we investigated the effect of 8-hour cold ischemia on the myocardial anti-oxidative defense system in a heterotopic rat heart transplantation model. METHODS: Lewis rat hearts were subjected to 30 or 480 minutes of 4 degrees C cold ischemia in Bretschneider cardioplegic solution with or without transplantation and reperfusion (30 or 240 minutes) into F344 recipients. Activity levels of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione S-transferase (GST), and concentrations of glutathione (GSH), glutathione disulfide (GSSG) and lipid hydroperoxides (LOOH) were analyzed in heart homogenates. For histology, cross-sections of the ventricles were stained with hematoxylin-eosin. RESULTS: Except for GST, enzyme activities and GSSG concentration increased and the glutathione redox ratio (GSH/GSH + 2GSSG) significantly decreased in 480-minute ischemic hearts compared with those with 30-minute ischemia. Reperfusion dramatically decreased both GSH and GSSG and increased LOOH formation but without severe histopathologic findings in the transplants. Applying a tree-structured classifier technique, GSH and LOOH were identified as significant features indicative of transplantation-induced oxidative stress. CONCLUSIONS: In the present study severe loss of glutathione and formation of LOOH indicated transplantation-induced oxidative stress in the rat heart; therefore, alterations of these parameters may hint at relevant deficits in the myocardial anti-oxidative defense and may also predict subsequent tissue damage.

Human receptor kinetics, tissue binding affinity, and stability of mometasone furoate.

Mometasone furoate (MF) is a topically used glucocorticoid with high anti-inflammatory potency. In contrast to the wealth of data derived from clinical studies, information about the molecular pharmacology of the compound is lacking or contradictory. Thus, we elucidated the characteristics of receptor binding kinetics and receptor affinity in a bioassay. Metabolite formation was determined in human plasma and lung tissue as well as binding affinity to human lung tissue. Fast and extensive association of MF to the human glucocorticoid receptor was observed while the dissociation of the MF-receptor complex was faster compared to fluticasone propionate (FP). The relative receptor affinity of MF was calculated as 2200 (dexamethasone = 100, FP = 1800) and confirmed in a bioassay measuring the induction of the glucocorticoid regulated protein CD163 in human monocytes. In plasma and human lung tissue MF formed a 9,11-epoxy degradation product. The binding affinity of MF to human lung tissue was low compared to FP due to fast redistribution from tissue into plasma. These molecular pharmacological properties are in accordance with clinical data.

Surgical treatment of renal cell carcinoma with intravascular extension.

Long-term survival after surgical treatment is possible in patients with renal cell carcinoma (RCC) extending in the right atrium. Different surgical techniques for the treatment of patients with RCC extending into the vena cava have been advocated, depending on the proximal extent of the tumor. We present and propose an algorithm regarding the operative strategy depending on the extent of tumor growth.

Cerebral oxygen saturation assessed by near-infrared spectroscopy during coronary artery bypass grafting and early postoperative cognitive function.

BACKGROUND: Cerebral oxygen saturation (ScO2) can be assessed by near-infrared spectroscopy. We investigated the correlation between early postoperative cognitive performance and intraoperative ScO2 in a prospective observational setting. METHODS: Forty-seven patients undergoing elective coronary artery bypass grafting with cardiopulmonary bypass underwent preoperative and postoperative neuropsychological evaluation. Patients were classified according to the presence or absence of postoperative cognitive dysfunction. Cognitive dysfunction was defined as an individual test score decrease of more than one standard deviation in two or more of the five tests. During operation ScO2 was continuously measured using an INVOS 4100 device. Cerebral oxygen saturation values were analyzed with reference to two cutoff points, which should reflect low cerebral oxygenation: an ScO2 less than 40% and a drop of more than 25% from individual baseline values. The duration and extent of ScO2 values below these two cutoff points was compared between the patients with and without cognitive dysfunction. RESULTS: Sixteen patients (34%) showed postoperative cognitive dysfunction. Cerebral oxygen saturation values less than 40% occurred in 17 patients for a mean (+/- standard error of the mean) of 17.2 +/- 6.5 minutes, whereas a decrease of more than 25% from baseline values occurred in 37 patients for 52.7 +/- 7.8 minutes. The duration and extent below the two cutoff ScO2 values was similar in patients with and without cognitive dysfunction. CONCLUSIONS: Intraoperative regional ScO2 as assessed by near-infrared spectroscopy with the INVOS 4100 device is not predictive for postoperative cognitive performance in patients undergoing coronary artery bypass grafting with cardiopulmonary bypass.

Paraneoplastic myasthenia gravis correlates with generation of mature naive CD4(+) T cells in thymomas.

Myasthenia gravis (MG) is the leading paraneoplastic manifestation of thymomas and is probably related to the capacity of thymomas to mature and export potentially autoreactive T cells. Why some thymomas are MG associated (MG+) and others are not (MG-) has been unclear. We addressed this question by comparing the percentages of intratumorous naive mature CD45RA+ thymocytes in 9 MG(+) and in 13 MG(-) thymomas by fluorescence-activated cell sorting analysis. Our results show that intratumorous naive CD4 T cells were present in all MG(+) thymomas and in one MG(-) thymoma with the development of MG only 2 months after surgery. By contrast, the percentage of naive CD4(+) T cells was significantly reduced in all 13 MG(-) thymomas (P <.0001). Alterations in intratumorous thymopoiesis were reflected by corresponding alterations of naive T-cell subset composition in the blood, in that only MG(-) patients had significantly decreased levels (P =.02) of naive CD4(+) T cells compared with age- and sex-matched control persons. We conclude that paraneoplastic MG is highly associated with the efficiency of thymomas to produce and export naive CD4(+) T cells. The acquisition of the CD45RA(+) phenotype on CD4(+) T cells during terminal intratumorous thymopoiesis is associated with the presence of MG in most thymoma patients.