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81.
Philipp E. Bartko Henrike Arfsten Maria K. Frey Gregor Heitzinger Noemi Pavo Anna Cho Stephanie Neuhold Timothy C. Tan Guido Strunk Christian Hengstenberg Martin Hülsmann Georg Goliasch 《JACC: Cardiovascular Imaging》2019,12(3):389-397
Objectives
This study sought to define the relationship between functional tricuspid regurgitation (TR) and mortality in patients with heart failure with reduced ejection fraction (HFrEF); and to establish the prognostic value of quantitative measures of TR severity (i.e., effective regurgitant orifice area [EROA] and regurgitant volume).Background
The significance of TR in chronic heart failure is controversial. Earlier studies have shown an independent impact of TR on mortality, whereas more recent evidence suggests myocardial impairment to be the driving force of mortality rather than TR itself. Earlier studies have used qualitative measures of TR severity, hence the prognostic value of more quantitative measures of TR severity (i.e., EROA and regurgitant volumes) remains unclear.Methods
We enrolled 382 patients with HFrEF on guideline-directed medical therapy and assessed TR EROA and regurgitant volume by Doppler/2-dimensional echocardiography. All-cause mortality was defined as the primary study endpoint.Results
TR severity was associated with the HFrEF phenotype with more symptoms (p = 0.004), higher neurohumoral activation (p < 0.001), progressive right-ventricular dilatation (p < 0.001), and impaired function (p < 0.001). Cox regression showed a strong association between quantitative measures of TR with mortality (all p < 0.001). Quantitative metrics of TR severity were consistently associated with mortality with a hazard ratio of 1.009 (95% confidence interval: 1.004 to 1.013; p < 0.001) per 0.01 cm2 increase of the EROA and of 1.013 (95% confidence interval: 1.007 to 1.020; p < 0.001) per 1-ml increase in regurgitant volume. Results remained unchanged after bootstrap- or clinical confounder-based adjustment. A spline curve pattern illustrates the association with mortality with thresholds for the EROA ≥0.2 cm2, and the regurgitant volume ≥20 ml with sustained excess mortality thereafter.Conclusions
This large-scale outcome study demonstrates the prognostic value of quantitative Doppler-echocardiographic measures of TR severity in HFrEF. The thresholds for EROA and TR regurgitant volume associated with mortality in our study fall within current ranges defining nonsevere TR. This may potentially impact therapeutic decision making, particularly timing of intervention. 相似文献82.
Czeiter E Mondello S Kovacs N Sandor J Gabrielli A Schmid K Tortella F Wang KK Hayes RL Barzo P Ezer E Doczi T Buki A 《Journal of neurotrauma》2012,29(9):1770-1778
Outcome prediction following severe traumatic brain injury (sTBI) is a widely investigated field of research. A major breakthrough is represented by the IMPACT prognostic calculator based on admission data of more than 8500 patients. A growing body of scientific evidence has shown that clinically meaningful biomarkers, including glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase-L1 (UCH-L1), and αII-spectrin breakdown product (SBDP145), could also contribute to outcome prediction. The present study was initiated to assess whether the addition of biomarkers to the IMPACT prognostic calculator could improve its predictive power. Forty-five sTBI patients (GCS score≤8) from four different sites were investigated. We utilized the core model of the IMPACT calculator (age, GCS motor score, and reaction of pupils), and measured the level of GFAP, UCH-L1, and SBDP145 in serum and cerebrospinal fluid (CSF). The forecast and actual 6-month outcomes were compared by logistic regression analysis. The results of the core model itself, as well as serum values of GFAP and CSF levels of SBDP145, showed a significant correlation with the 6-month mortality using a univariate analysis. In the core model, the Nagelkerke R(2) value was 0.214. With multivariate analysis we were able to increase this predictive power with one additional biomarker (GFAP in CSF) to R(2)=0.476, while the application of three biomarker levels (GFAP in CSF, GFAP in serum, and SBDP145 in CSF) increased the Nagelkerke R(2) to 0.700. Our preliminary results underline the importance of biomarkers in outcome prediction, and encourage further investigation to expand the predictive power of contemporary outcome calculators and prognostic models in TBI. 相似文献
83.
Elena Magrini Alessandra Villa Francesca Angiolini Andrea Doni Giovanni Mazzarol Noemi Rudini Luigi Maddaluno Mina Komuta Baki Topal Hans Prenen Melitta Schachner Stefano Confalonieri Elisabetta Dejana Fabrizio Bianchi Massimiliano Mazzone Ugo Cavallaro 《The Journal of clinical investigation》2014,124(11):5085
84.
Use of perfluorohexyloctane as a long-term internal tamponade agent in complicated retinal detachment surgery. 总被引:9,自引:0,他引:9
Bernd Kirchhof David Wong Jan Van Meurs Ralf D Hilgers Marc Macek Noemi Lois Norbert F Schrage 《American journal of ophthalmology》2002,133(1):95-101
PURPOSE: To report the use of perfluorohexyloctane, a liquid semifluorinated alkane that is heavier than water, as an internal tamponade agent in surgery for complicated retinal detachments. DESIGN: A consecutive interventional case series from three study centers. METHODS: In 23 consecutive eyes (23 patients, 19 men and four women, mean +/- standard deviation (SD) age of 58.5 years +/- 16.1) perfluorohexyloctane was used for long-term internal tamponade. Included were eyes with complicated retinal detachment involving the lower two quadrants of the fundus. Excluded were patients with diseases in the fellow eye or severe systemic disease. A pars plana vitrectomy was performed, including membrane peeling and retinotomy where necessary. RESULTS: The mean duration for perfluorohexyloctane being left in situ was 76 days (SD 37.64) (range, 35-202 days). Four weeks following the removal of perfluorohexyloctane 19 of the 23 patients had total reattachment of the retina; three eyes had a recurrence of retinal detachment. One patient was lost to follow-up. The mean follow-up after perfluorohexyloctane removal was 97 days (range, 48 to 169 days). Cataract formation or progression was noted in nine of the 10 eyes. There were two cases with high intraocular pressures. Dispersion into small droplets was observed as early as 3 days postoperatively in three of the 23 patients. At least 12 of the 23 patients had an obvious dispersion by the time of perfluorohexyloctane removal. There was no sign of optic atrophy, retinal necrosis, or retinal vascular occlusion. CONCLUSION: Perfluorohexyloctane was tolerated as a long-term internal tamponade agent without obvious signs of damage to the retina or optic disk. Of all the complications noted, the most common was that of dispersion of the perfluorohexyloctane bubble into droplets. 相似文献
85.
The most defined and reproducible electroencephalographic manifestation of oxygen poisoning in animals culminates in a generalized synchronous electrical discharge and very often in clinical convulsions. The amplitude and frequency of the electrocortical activity (EEG) in the preseizure phase was studied in unanesthetized rats during exposure to hyperbaric oxygen. The preseizure EEG (electrocorticogram) of rats breathing 6 ATA (atmospheres absolute) oxygen showed reduction in the mean frequency starting 7 min before the appearance of the first electrical discharge and a decrease of the mean amplitude starting about 3 min before the onset of the first electrical discharge. Our findings demonstrated that there is a progressive deterioration of the cortical electrical activity in rats exposed to high oxygen pressure. This suggests that the toxic effect of oxygen on the brain is cumulative and interferes with its normal metabolic and electrochemical processes. 相似文献
86.
Mayorga ME Sanchis D Perez de Santos AM Velasco A Dolcet X Casanova JM Baradad M Egido R Pallares J Espurz N Benitez D Mila J Malvehy J Castel T Comella JX Matias-Guiu X Vilella R Marti RM 《Melanoma research》2006,16(2):127-135
Standard antineoplastic treatment for metastatic melanoma is ineffective in the large majority of patients. Therefore, alternative approaches need to be investigated. STI571 is a new antineoplastic compound, which selectively inhibits the tyrosine kinase activity of ABL, c-Kit and platelet-derived growth factor receptor (PDGFR). Melanoma may express all of these proteins. The aim of this study was to investigate whether STI571 inhibits the in-vitro growth of melanoma cells. Nineteen cell lines were obtained from four primary and 15 metastatic melanomas of cutaneous origin. The percentages of positive cells for the putative targets of STI571 were as follows: ABL, 41-100%; c-Kit, 8-97%; PDGFR-alpha, 41-98%; PDGFR-beta, 51-99%. 3-(4,5-Dimethylthiazol-yl)-2,5-diphenyltetrazolium (MTT) and viability assays showed that STI571 clearly inhibits the proliferation of eight of the 19 (42.1%) cell lines. No relationship could be established between the expression of c-Kit, ABL, PDGFR-alpha or PDGFR-beta and the response of cell lines to STI571. Our study shows, for the first time, an antiproliferative effect of STI571 on human melanoma cell lines of cutaneous origin, raising the possibility of the future clinical use of STI571. The identification of the target of STI571 in human cutaneous melanoma cells would allow the selection of patients who could benefit from this treatment. 相似文献
87.
Targeting ADAM-mediated ligand cleavage to inhibit HER3 and EGFR pathways in non-small cell lung cancer 总被引:10,自引:0,他引:10
Zhou BB Peyton M He B Liu C Girard L Caudler E Lo Y Baribaud F Mikami I Reguart N Yang G Li Y Yao W Vaddi K Gazdar AF Friedman SM Jablons DM Newton RC Fridman JS Minna JD Scherle PA 《Cancer cell》2006,10(1):39-50
We describe here the existence of a heregulin-HER3 autocrine loop, and the contribution of heregulin-dependent, HER2-mediated HER3 activation to gefitinib insensitivity in non-small cell lung cancer (NSCLC). ADAM17 protein, a major ErbB ligand sheddase, is upregulated in NSCLC and is required not only for heregulin-dependent HER3 signaling, but also for EGFR ligand-dependent signaling in NSCLC cell lines. A selective ADAM inhibitor, INCB3619, prevents the processing and activation of multiple ErbB ligands, including heregulin. In addition, INCB3619 inhibits gefitinib-resistant HER3 signaling and enhances gefitinib inhibition of EGFR signaling in NSCLC. These results show that ADAM inhibition affects multiple ErbB pathways in NSCLC and thus offers an excellent opportunity for pharmacological intervention, either alone or in combination with other drugs. 相似文献
88.
Ott K Vogelsang H Marton N Becker K Lordick F Kobl M Schuhmacher C Novotny A Mueller J Fink U Ulm K Siewert JR Höfler H Keller G 《International journal of cancer. Journal international du cancer》2006,119(12):2885-2894
We evaluated DNA polymorphisms in the thymidylate synthase (TS) and 5,10-methylene-tetrahydrofolate reductase (MTHFR) genes for an association with response and survival in locally advanced gastric cancer treated with 5-FU based preoperative chemotherapy (CTx). DNA of 238 patients (CTx-group: total n = 135, completely resected (R0) n = 102; without CTx: R0 n = 103) was isolated from blood or from nontumorous tissues. In the CTx-group, genotyping of the tandem repeat and the G/C polymorphism in the triple repeat in the promoter region of the TS gene and of the C677T polymorphism of the MTHFR gene was performed. None of the TS or MTHFR genotypes were associated with histopathological response and only the TS tandem repeat polymorphism was significantly related to survival (all patients n = 135, p = 0.002; R0 resected patients n = 102, p = 0.007; log-rank test). Multivariate analysis revealed ypN (p < 0.001) and the TS tandem repeat polymorphism as independent prognostic factors in the CTx-R0-group (p = 0.003). Analyzing the prognostic significance of the TS polymorphisms in the R0-group without CTx, TS genotypes were not significantly associated with survival. Comparing survival between R0 patients with and without CTx in the respective TS genotype groups of the tandem repeat polymorphism, a significant survival benefit for the patients with CTx was found for the 2rpt/2rpt (n = 49; p = 0.002) and 2rpt/3rpt genotypes (n = 99; p = 0.004), but not for the 3rpt/3rpt genotype (n = 57; p = 0.93). Patients' survival after CTx was associated with the TS tandem repeat polymorphism. CTx did not improve survival of patients with the 3rpt/3rpt genotype. Thus, a different therapy might be more appropriate for these patients. 相似文献
89.
90.