Interdisciplinary consensus on indications for transfemoral transcatheter aortic valve implantation (TF-TAVI) : Joint Consensus Document of the Arbeitsgemeinschaft Leitende Kardiologische Krankenhausärzte e.V. (ALKK) and cooperating Cardiac Surgery Departments.

Indications for TF-TAVI (transfemoral transcatheter aortic valve implantation) are rapidly changing according to increasing evidence from randomized controlled trials. Present trials document the non-inferiority or even superiority of TF-TAVI in intermediate-risk patients (STS-Score 4-8%) as well as in low-risk patients (STS-Score < 4%). However, risk scores exhibit limitations and, as a single criterion, are unable to establish an appropriate indication of TF-TAVI vs transapical TAVI vs SAVR (surgical aortic valve replacement). The ESC (European Society of Cardiology)/EACTS (European Association for Cardio-Thoracic Surgery) guidelines 2017 and the German DGK (Deutsche Gesellschaft für Kardiologie)/DGTHG (Deutsche Gesellschaft für Thorax-, Herz- und Gefäßchirurgie) commentary 2018 offer a framework for the selection of the best therapeutic method, but the individual decision is left to the discretion of the heart teams. An interdisciplinary TAVI consensus group of interventional cardiologists of the ALKK (Arbeitsgemeinschaft Leitende Kardiologische Krankenhausärzte e.V.) and cardiac surgeons has developed a detailed consensus on the indications for TF-TAVI to provide an up-to-date, evidence-based, comprehensive decision matrix for daily practice. The matrix of indication criteria includes age, risk scores, contraindications against SAVR (e.g., porcelain aorta), cardiovascular criteria pro TAVI, additional criteria pro TAVI (e.g., frailty, comorbidities, organ dysfunction), contraindications against TAVI (e.g., endocarditis) and cardiovascular criteria pro SAVR (e.g., bicuspid valve anatomy). This interdisciplinary consensus may provide orientation to heart teams for individual TAVI-indication decisions. Future adaptations according to evolving medical evidence are to be expected. Interdisciplinary consensus on indications for transfemoral transcatheter aortic valve implantation (TF-TAVI).

Structure of the Lightest Tin Isotopes.

We link the structure of nuclei around ^{100}Sn, the heaviest doubly magic nucleus with equal neutron and proton numbers (N=Z=50), to nucleon-nucleon (NN) and three-nucleon (NNN) forces constrained by data of few-nucleon systems. Our results indicate that ^{100}Sn is doubly magic, and we predict its quadrupole collectivity. We present precise computations of ^{101}Sn based on three-particle-two-hole excitations of ^{100}Sn, and we find that one interaction accurately reproduces the small splitting between the lowest J^{π}=7/2^{+} and 5/2^{+} states.

[Wide-field fundus autofluorescence in non-infectious posterior uveitis]. / Weitwinkelfundusautofluoreszenz bei nichtinfektiöser Uveitis posterior.

BACKGROUND: Posterior uveitis comprises a heterogeneous group of diseases with inflammatory alterations of the posterior fundus and is a common cause of visual impairment and blindness. The goal of this study was to evaluate the diagnostic value of wide-field fundus autofluorescence (FAF) in patients with non-infectious posterior uveitis and chorioretinal alterations. MATERIAL AND METHODS: In this study 73 eyes from 51 patients were included. Best-corrected visual acuity, wide-field color and FAF images achieved by a wide-field scanning laser opththalmoscope (SLO, Optomap P200Tx, Optos PLC, Dunfermline UK) and a full ophthalmological examination were obtained from each patient. A systematic analysis of chorioretinal alterations detected with FAF and color images was conducted followed by the evaluation of the diagnostic information of wide-field FAF compared to the clinical finding and wide-field color images. RESULTS: Of the 73 eyes included in the study 52 showed peripheral alterations. In 32 cases wide-field FAF images revealed a greater number and more extensive chorioretinal alterations than the corresponding wide-field color images of the posterior fundus. CONCLUSIONS: In this study wide-field FAF images showed more chorioretinal alterations than seen in funduscopy or in color SLO images. Therefore, wide-field FAF images offer important additional information for detection and documentation of peripheral and central chorioretinal alterations.

CALUX measurements: statistical inferences for the dose-response curve.

Chemical Activated LUciferase gene eXpression [CALUX] is a reporter gene mammalian cell bioassay used for detection and semi-quantitative analyses of dioxin-like compounds. CALUX dose-response curves for 2,3,7,8-tetrachlorodibenzo-p-dioxin [TCDD] are typically smooth and sigmoidal when the dose is portrayed on a logarithmic scale. Non-linear regression models are used to calibrate the CALUX response versus TCDD standards and to convert the sample response into Bioanalytical EQuivalents (BEQs). Several complications may arise in terms of statistical inference, specifically and most important is the uncertainty assessment of the predicted BEQ. This paper presents the use of linear calibration functions based on Box-Cox transformations to overcome the issue of uncertainty assessment. Main issues being addressed are (i) confidence and prediction intervals for the CALUX response, (ii) confidence and prediction intervals for the predicted BEQ-value, and (iii) detection/estimation capabilities for the sigmoid and linearized models. Statistical comparisons between different calculation methods involving inverse prediction, effective concentration ratios (ECR(20-50-80)) and slope ratio were achieved with example datasets in order to provide guidance for optimizing BEQ determinations and expand assay performance with the recombinant mouse hepatoma CALUX cell line H1L6.1c3.

Reduction of regulatory T cells in skin lesions but not in peripheral blood of patients with systemic scleroderma.

OBJECTIVE: To determine the frequency and suppressive capacity of regulatory T cells (T(reg)) and their association with clinical parameters in patients with systemic scleroderma (SSc). METHODS: Peripheral blood from 25 patients with SSc, 15 patients with localised scleroderma (LS) and 29 healthy controls (HC) was studied. Analysis of CD4(+) forkhead box P3 (Foxp3)(+) and CD4(+)CD25(++)Foxp3(+) T(reg) subpopulations was carried out by flow cytometry and cell proliferation was quantified by (3)H-thymidine incorporation. Quantitative analysis of T(reg) was further performed in skin biopsies from 17 patients with SSc and 21 patients with LS using anti-CD4 and anti-Foxp3 monoclonal antibodies for immunohistochemistry. RESULTS: The frequency of CD4(+)Foxp3(+) and CD4(+)CD25(++)Foxp3(+) T(reg) in peripheral blood from patients with SSc was not significantly different from that of patients with LS or HC. The suppressive capacity of CD4(+)CD25(++) T(reg) in SSc was also found to be similar to that of HC. Phenotypic and functional data revealed no significant difference between the limited or diffuse form of SSc. Moreover, therapy with bosentan showed no significant effect on the frequency of T(reg) during the course of the disease. However, the frequency of T(reg) in skin lesions from patients with SSc or LS, determined as the percentage of CD4(+) cells expressing Foxp3 in the inflammatory infiltrate, was significantly reduced compared with other inflammatory skin diseases. CONCLUSION: These results indicate that although the authors found no defect in the frequency or function of peripheral T(reg) subpopulations, the reduction of CD4(+)Foxp3(+) T(reg) in the skin of patients with SSc may be important in the pathogenesis of the disease.

Characterization of regulatory T cells in patients with dermatomyositis.

The purpose of this study was to characterize regulatory T cells (T(reg)) in skin lesions and peripheral blood from patients with dermatomyositis (DM) and to determine the serum levels of regulatory cytokines in the disease. In skin biopsy specimens from patients with DM, immunohistochemistry was performed for CD4(+), CD25(+), forkhead/winged helix transcription factor (FoxP3)(+), transforming growth factor (TGF)-ß(+) and interleukin (IL)-10(+) cells. Additionally, we defined the number of T(reg) subpopulations in peripheral blood by flow cytometry using monoclonal antibodies against CD4, CD25, FoxP3, CD45RO, CD95, CCR4 and CLA. The levels of TGF-ß and IL-10 were also determined in serum samples from patients with DM by enzyme-linked immunosorbent assays. Controls included patients with cutaneous lupus erythematosus, psoriasis and atopic dermatitis (AD) as well as healthy donors. The frequency of FoxP3(+) cells was significantly reduced in skin lesions from patients with DM (p < 0.001) compared to psoriasis and AD. Moreover, the number of cells positive for TGF-ß was lower in DM than in psoriasis and AD, while IL-10(+) cells were significantly reduced only compared to psoriasis. The number of CD4(+)CD25(++)FoxP3(+) T(reg) in the peripheral blood of patients with DM was significantly reduced compared to healthy controls (p < 0.05), whereas other cell populations showed no significant differences. Finally, TGF-ß and IL-10 serum levels were significantly lower in patients with DM compared to healthy controls (p < 0.05). These data suggest that the depletion of T(reg) and their main effector cytokines in the skin and the serum of patients with DM may be an important factor in the pathogenesis of the disease.

A new certified reference material for benzene measurement in air on a sorbent tube: development and proficiency testing.

A certified matrix reference material (CRM) for the measurement of benzene in ambient air has been developed at Laboratoire National de Métrologie et d'Essais. The production of these CRMs was conducted using a gravimetric method fully traceable to the International System of Units. The CRMs were prepared by sampling an accurate mass of a gaseous primary reference material of benzene, using a high-precision laminar flowmeter and a mass flow controller, with a PerkinElmer sampler filled with Carbopack™ X sorbent. The relative standard deviations obtained for the preparation of a batch of 20 tubes loaded with 500 ng of benzene were below 0.2%. Each CRM is considered independent from the others and with its own certified value and an expanded uncertainty estimated to be within 0.5%, lower than the uncertainties of benzene CRMs already available worldwide. The stability of these materials was also established up to 12 months. These CRMs were implemented during proficiency testing, to evaluate the analytical performances of seven French laboratories involved in benzene air monitoring.

CD40/CD154 system and pro-inflammatory cytokines in young healthy male smokers without additional risk factors for atherosclerosis.

OBJECTIVE AND DESIGN: Atherosclerosis, as an inflammatory disease, is characterized by pathologically altered levels of cytokines. We investigated whether smoking affects the CD40/CD154 system and pro-inflammatory cytokines in young males without other risk factors for atherosclerosis. SUBJECTS: Young male smokers (n=13) and 14 non-smoking controls were investigated. METHODS: The differences in CD40/CD154 system and serum cytokines between the groups were measured using flow cytometry and ELISA. RESULTS: In smokers, there was a strong trend (P<0.06) for increased CD40 expression on platelets as compared with non-smokers. However, there were no significant differences in CD40 expression on monocytes or in CD154 expression on platelets and T-cells between smokers and non-smokers. There was a strong trend for increased platelet-monocyte aggregates in smokers (P<0.06). Also, smokers had slightly but not significantly elevated hsCRP and IL-6 levels, and slightly decreased TNF-alpha and MCP-1. Interestingly, IL-18, a cytokine which has the ability to promote both Th1 and Th2 responses, was significantly decreased in smokers group (P=0.03 vs controls). CONCLUSIONS: In young healthy males, smoking is not associated with dramatic changes in CD40/CD154 system. However, cigarette smoke alters the secreted cytokine profile, leading to significant decrease in systemic IL-18 levels.

Elevated VEGF-plasma levels in young patients with mild essential hypertension.

BACKGROUND: Growing evidence shows that inflammation plays a pivotal role in the pathophysiology of essential hypertension (EH). Vascular endothelial cell growth factor (VEGF) is currently discussed as a possible mediator of inflammation. To investigate the hypothesis that VEGF plays a role as an inflammatory mediator in EH we performed the present pilot study of young patients in a very early stage of EH. MATERIALS AND METHODS: 15 young patients with mild EH [33.8 +/- 7.3 years, systolic blood pressure (SBP): 143.8 +/- 10.5 mmHg, diastolic blood pressure (DBP): 88.2 +/- 11.1 mmHg, mean arterial pressure (MAP) 106.6 +/- 10.4 mmHg] and 15 healthy controls (31.7 +/- 10.6 years) were examined. Blood was drawn from a peripheral vein and serum levels of VEGF, monocyte-chemoattractant-protein (MCP)-1, high-sensitivity C-reactive protein (hsCRP), interleukin (IL)-6, and tumour-necrosis-factor (TNF)-alpha were measured via commercially available enzyme-linked immunoassays. RESULTS: Hypertensives showed increased plasma levels of VEGF (P < 0.05) and MCP-1 (P < 0.05). VEGF positively correlated with MAP (r = 0.46, P < 0.05) and MCP-1 (r = 0.63, P < 0.01). Multivariate analysis demonstrated VEGF to be an independent predictor of MCP-1 levels. Furthermore, hypertensives had higher levels of hsCRP (P < 0.01), IL-6 (P < 0.001) and TNF-alpha (P < 0.05). IL-6 levels correlated with SBP (r = 0.59, P < 0.001), DBP (r = 0.67, P < 0.001) and MAP (r = 0.46, P < 0.001). A significant positive correlation was also found between hsCRP levels and SBP (r = 0.39, P < 0.05). CONCLUSIONS: This pilot study demonstrates that in an early state of EH, inflammatory pathways have already been activated. Besides classical pro-inflammatory cytokines, VEGF serum levels are significantly elevated. The positive correlation of VEGF with MCP-1 is suggestive for the already described induction of MCP-1 via VEGF.

Novel arthropod repellent, BioUD, is an efficacious alternative to deet.

For >50 yr, N,N-diethyl-3-methylbenzamide (deet) has been the standard for arthropod repellents and has been an important tool to protect people from disease agents carried by ticks, mosquitoes, and other arthropods. However, some people avoid using deet because of concerns about adverse health effects. In 2007, a new repellent, BioUD, with the active ingredient 7.75% 2-undecanone, originally derived from wild tomato (Lycopersicon hirsutum Dunal f. glabratum C. H. Müll) plants, was registered by the U.S. Environmental Protection Agency. In the current study, repellent efficacy of BioUD was compared using arm-in-cage studies with 7 and 15% deet against the mosquitoes Aedes aegypti (L.) and Aedes albopictus Skuse. No differences were found in mean repellency over 6 h after application between BioUD versus 7 and 15% deet for Ae albopictus. For Ae. aegypti, no differences were found over the same time period for 7% deet. Compared with 15% deet, BioUD mean repellency was lower over the 6-h test period. Human subject field trials were conducted in North Carolina, United States, and Ontario, Canada, comparing the repellency of BioUD to products containing 25 and 30% deet. BioUD provided the same repellency or was more efficacious than 25 and 30% deet, respectively, in these studies. Laboratory trials were conducted to determine the repellent activity of BioUD against the American dog tick, Dermacentor variabilis (Say), on human skin and cloth. BioUD repelled ticks at least 2.5 h after application to human skin. On cloth, no differences in mean repellency were found through 8 d after application between BioUD and 7% deet. In a two-choice test for BioUD versus 15% deet on filter paper, ticks spent significantly more time on the deet-treated surface than the BioUD-treated surface. Based on these studies in toto, BioUD is an efficacious alternative to deet in its repellent activity.

Platelets contribute to enhanced MCP-1 levels in patients with chronic heart failure.

BACKGROUND: Increasing scientific data suggest a role for inflammation in chronic heart failure (CHF), but up to now the exact mechanisms are still not clear. Recently, platelets were identified as inducing inflammation partly by releasing cytokines. This new aspect necessitates further studies about the contribution of platelets for the inflammatory setting of CHF. METHODS: 50 CHF patients (mean 66.9 (SD 12.6) years, mean EF 22.1% (SD 9.1)) and 25 healthy controls (mean 63.6 (SD 10.2) years) were examined. MCP-1 serum levels were measured via EIA, expression of platelet CD154 by flow cytometry. In in-vitro experiments activated platelets were cocultured with human umbilical vein endothelial cells (HUVEC) in the presence and absence of anti-CD154 antibodies. MCP-1 in the supernatants was measured by EIA. RESULTS: CHF patients showed significantly enhanced MCP-1 levels (median: 191.8; 25th centile: 153.7; 75th centile: 227.1 pg/ml vs median: 101.0; 25th centile: 86.7; 75th centile: 117.5 pg/ml, p<0.001). MCP-1 levels positively correlated with severity of CHF. In the cell coculture model activated platelets were able to significantly induce MCP-1 release from HUVEC in a CD154-dependent manner. Furthermore, CHF patients showed enhanced platelet CD154 expression with a positive correlation with MCP-1 levels. Aspirin therapy had no influence on either CD154 expression or MCP-1 levels. CONCLUSIONS: Platelets can contribute to enhanced MCP-1 levels in CHF. MCP-1 is markedly elevated in serum of CHF patients showing a direct correlation with the severity of symptoms and the degree of left ventricular dysfunction. Further studies are required to test whether MCP-1 blocking or sophisticated anti-platelet strategies may represent new therapeutic options in CHF.

Course of mitogen-stimulated T lymphocytes in cancer patients treated with Viscum album extracts.

BACKGROUND: In a prospective observational study, the impact of two different dose regimes of a commercially available fermented Viscum album L. extract (VA-E, Iscador) on the function of T lymphocytes from cancer patients was investigated. PATIENTS AND METHODS: A total of 71 cancer patients were enrolled. These patients attended two different sections of a tumor outpatient clinic which are used to apply different VA-E escalation schemes. Our hypothesis was that a rapid dose escalation of subcutaneously applied VA-E may induce strong local reactions at the injection side (>3 cm diameter) and may have an effect on the functional competence of T lymphocytes (mitogen-activated interleukin-2 receptor alpha chain), which was recorded over an observation period of six month. RESULTS: Within this observation period, a decline of stimulated T cell function was observed, particularly in patients with colorectal or prostate cancer; this decline was not seen in patients with breast cancer (who received lower mean concentrations per month) nor in patients with dose adaptation in response to too strong local reactions. CONCLUSION: With respect to T-cell function, our results indicate that in patients without local reactions, a long lasting mistletoe extract application should be withheld periodically to allow T-cell reactivity to recover.

The application of microbore UPLC/oa-TOF-MS and 1H NMR spectroscopy to the metabonomic analysis of rat urine following the intravenous administration of pravastatin.

The metabonomic effects of hepatotoxic doses of pravastatin on the urinary metabolic profiles of female rats have been investigated using ultra performance liquid chromatography (UPLC)-oa-TOF-MS and, independently, by (1)H NMR spectroscopy. UPLC was performed using a 1 mm microbore column packed with 1.7 microm particles. Examination of the data obtained from the individual animals, aided by statistical interpretation of the data, made it possible to identify potential markers for toxicological effects, with both NMR and UPLC-MS analysis highlighting distinct changes in the urinary metabolite profiles. These markers, which included elevated taurine and creatine, as well as bile acids, were consistent with hepatotoxicity in some animals, and this hypothesis was supported by histopathological and clinical chemistry findings. The analytical data from both techniques could be used to define a metabolic "trajectory" as toxicity developed and to provide an explanation for the lack of hepatotoxicity for one of the animals. The two analytical approaches (UPLC-MS and NMR) were found to be complementary whilst the use of a 1mm i.d. x 100 mm column reduced the amount of sample required for analysis to 2 microL, compared with 10 microL for a 2.1mm i.d. x 100 mm column. The 1mm i.d. column also provided increased signal-to-noise without loss of chromatographic efficiency.

Low number of regulatory T cells in skin lesions of patients with cutaneous lupus erythematosus.

OBJECTIVE: To define the phenotype and function of CD4+,CD25+ regulatory T cells (Treg) in patients with cutaneous lupus erythematosus (CLE), a heterogeneous autoimmune disease characterized primarily by inflammatory skin lesions. METHODS: The number of Treg in skin specimens obtained from patients with various subtypes of CLE was investigated by immunohistochemical analysis, using anti-Foxp3 and anti-CD4 monoclonal antibodies. Furthermore, characterization of peripheral blood CD4+,CD25+ Treg from normal healthy donors and patients with CLE was carried out by flow cytometry, analyzing the expression of Foxp3 and Treg subpopulations. We also purified CD4+,CD25(high) Treg obtained from patients with CLE and tested the sensitivity of these cells to CD95L-mediated apoptosis. RESULTS: Quantitative analysis of CD4+ T cells in skin lesions from patients with CLE revealed that the number was similar to that in lesions from patients with other chronic inflammatory diseases, but the number of Foxp3+ Treg in CLE was significantly reduced. There was no correlation between disease subtype and the frequency of Foxp3+ Treg in the skin of patients with CLE. In peripheral blood, no significant differences were observed in the number and phenotype of CD4+,CD25+ Treg or in the sensitivity to apoptosis of CD4+,CD25(high) Treg derived from patients with CLE and those derived from normal healthy donors. CONCLUSION: These data suggest that an organ-specific abnormality of Treg in the skin underscores the importance of analyzing Treg in the affected tissue. Such a local process might give insight into the pathogenic mechanisms of CLE and differs from a global peripheral dysfunction as reported for patients with a systemic manifestation of the disease.

Increased prolactin in acute coronary syndromes as putative Co-activator of ADP-stimulated P-selectin expression.

Prolactin and leptin are newly recognized platelet co-stimulators due to enhancement of ADP-induced platelet aggregation. The aim of our study was to assess whether both hormones prolactin and leptin play a role as co-activators of platelet activation in patients with acute coronary syndromes. Twenty-one patients with acute coronary syndromes, 10 with stable angina pectoris and 10 controls were studied. Patients with acute coronary syndromes showed significantly higher prolactin and leptin values and a significant increased P-selectin expression on platelets compared to patients with stable angina pectoris or controls. However, patients with acute myocardial infarction as a subgroup of acute coronary syndromes showed the highest prolactin levels as well as ADP stimulated P-selectin expression. In the myocardial infarction subgroup prolactin values showed a significant correlation to ADP stimulated P-selectin expression on platelets (r (2)=0.41; p=0.025), whereas leptin was not correlated. Our data indicate an association between increased prolactin values and enhanced P-selectin expression on platelets in patients with acute coronary syndromes. Therefore, the stress hormone prolactin could be a co-stimulator of platelet activation in these patients. In contrast, the putative platelet activator leptin does not seem to play a major role in acute coronary syndromes.

A multi-analytical platform approach to the metabonomic analysis of plasma from normal and Zucker (fa/fa) obese rats.

Plasma obtained from 20 week old normal Wistar-derived and Zucker (fa/fa) rats was analysed using a number of different analytical methodologies to obtain global metabolite profiles as part of metabonomic investigations of animal models of diabetes. Samples were analysed without sample pre-treatment using 1H NMR spectroscopy, after acetonitrile solvent protein precipitation by ultra-performance liquid chromatography-MS (UPLC-MS) and after acetonitrile protein precipitation and derivatisation for capillary gas chromatography-MS (GC-MS). Subsequent data analysis using principal components analysis revealed that all three analytical platforms readily detected differences between the plasma metabolite profiles of the two strains of rat. There was only limited overlap between the metabolites detected by the different methodologies and the combination of all three methods of metabolite profiling therefore provided a much more comprehensive profile than would have been provided by their use individually.

Delay of neutrophil apoptosis in acute coronary syndromes.

Apoptosis of polymorphonuclear neutrophils (PMN) is currently discussed as a key event in the control of inflammation. This study determined PMN apoptosis and its underlying mechanisms in controls (C), patients with stable (SAP) or unstable angina (UAP), and with acute myocardial infarction (AMI). Blood was drawn from 15 subjects of each C, SAP, UAP, and AMI. Apoptosis was measured by flow cytometry in isolated PMN (propidium iodide staining) and PMN from whole blood (CD16, FcgammaRIII). Serum cytokines were determined by enzyme-linked immunosorbent assay. Apoptosis of isolated PMN was delayed significantly in acute coronary syndromes (ACS) as compared with SAP or C (C, 51.2+/-12.6%; SAP, 44.9+/-13.6%; UAP, 28.4+/-10.1%; AMI, 20.3+/-8.5%; AMI or UAP vs. SAP or C, P<0.001). These results were confirmed by measurement of PMN apoptosis in cultured whole blood from patients and controls. Moreover, serum of patients with ACS markedly reduced apoptosis of PMN from healthy donors. Analysis of patients' sera revealed significantly elevated concentrations of tumor necrosis factor alpha, interferon-gamma (IFN-gamma), granulocyte macrophage-colony stimulating factor (GM-CSF), and interleukin (IL)-1beta in ACS (vs. C and SAP). IFN-gamma, GM-CSF, and IL-1beta significantly delayed PMN apoptosis in vitro. Furthermore, coincubation of PMN with adenosine 5'-diphosphate-activated platelets significantly inhibited PMN apoptosis as compared with coculture with unstimulated platelets. This study demonstrates a pronounced delay of PMN apoptosis in UAP and AMI, which may result from increased serum levels of IFN-gamma, GM-CSF, and IL-1beta and from enhanced platelet activation. Therapeutical modulation of these determinants of PMN lifespan may provide a new concept for the control of inflammation in ACS.

[Retrospective study of malignant melanoma patients treated with mistletoe extracts]. / Retrospektive Untersuchung von Patienten mit malignem Melanom unter einer Misteltherapie.

OBJECTIVE: The aim of the present investigation was to analyze survival time and survival rate of all patients with malignant melanoma who had been counseled at the Tumorambulanz Herdecke of the Community Hospital Herdecke. PATIENTS AND METHODS: 284 melanoma patients were included in a retrospective questionnaire study. Only those patients were considered for analysis in whom the prognostic factors histology, tumor localization, and Clark level were known. The data of the study population were compared with patient data obtained from the literature. RESULTS: 94 patients were included in the analysis. 66 of whom had received and 7 had not received mistletoe treatment, in the remaining 21 patients there was no information whether or not mistletoe treatment had been given. Thus, we did our study without a clearly defined internal control group. The median survival time among patients treated with mistletoe had been 14.1 years. The 5- and 10-year survival rates were 80 and 68% for the mistletoe-treated patients, respectively. DISCUSSION: The 5-year survival rate of the mistletoe-treated patients is comparable to that of patients without mistletoe therapy while the 10-year survival rate is a little bit lower. This may be due to the fact that, in contrast to the patients from the relevant literature, 33.3% of the patients suffered from lymph node and/or distant metastases already before counseling the Tumorambulanz Herdecke. Moreover, 50% of our patients had melanoma of Clark level IV in contrast to 22.2% or 31% in the relevant literature. CONCLUSIONS: In spite of the theoretical reservations against mistletoe treatment in melanoma patients, our retrospective analysis did not show any clues about disadvantages of mistletoe treatment in melanoma patients. A controlled prospective study therefore should prove the efficacy of a mistletoe therapy in patients with malignant melanoma.

Upregulation of CD40-CD40 ligand (CD154) in patients with acute cerebral ischemia.

BACKGROUND AND PURPOSE: Inflammation and hypercoagulability contribute to the development of acute cerebral ischemia. Both can be mediated by the CD40 system. This study investigated whether the CD40 system and related mediators are upregulated in patients with transient ischemic attack (TIA) or stroke. METHODS: Seventeen patients with TIA, 60 patients with complete stroke, and 15 control subjects were investigated. CD154 and P-selectin were analyzed on platelets and CD40 on monocytes during and 3 months after acute cerebral ischemia by double-label flow cytometry. Blood concentrations of soluble CD154 and monocyte chemoattractant protein-1 (MCP-1) were evaluated. RESULTS: Our main findings are as follows: (1) patients with acute cerebral ischemia showed a significant increase of CD154 on platelets and CD40 on monocytes compared with controls; (2) plasma levels of soluble CD154 were significantly higher in these patients; (3) these patients had significantly higher numbers of prothrombotic platelet-monocyte aggregates; (4) the chemoattractant MCP-1 was significantly elevated in cerebral ischemia; and (5) at 3 months' follow-up, upregulation of CD154 still persisted in patients with previous acute cerebral ischemia. CONCLUSIONS: Patients with acute cerebral ischemia show upregulation of the CD40 system, which might contribute to the known proinflammatory, proatherogenic, and prothrombotic milieu found in these patients.