Background: Estimating the prognosis in malignant pleural mesothelioma (MPM) remains challenging. Thus, the prognostic relevance of Ki67 was studied in MPM. Methods: Ki67 index was determined in a test cohort of 187 cases from three centres. The percentage of Ki67-positive tumour cells was correlated with clinical variables and overall survival (OS). The prognostic power of Ki67 index was compared with other prognostic factors and re-evaluated in an independent cohort ( n =98). Results: Patients with Ki67 higher than median (>15%) had significantly ( P <0.001) shorter median OS (7.5 months) than those with low Ki67 (19.1 months). After multivariate survival analyses, Ki67 proved to be—beside histology and treatment—an independent prognostic marker in MPM (hazard ratio (HR): 2.1, P <0.001). Interestingly, Ki67 was prognostic exclusively in epithelioid ( P <0.001) but not in non-epithelioid subtype. Furthermore, Ki67 index was significantly lower in post-chemotherapy samples when compared with chemo-naive cases. The prognostic power was comparable to other recently published prognostic factors (CRP, fibrinogen, neutrophil-to-leukocyte ratio (NLR) and nuclear grading score) and was recapitulated in the validation cohort ( P =0.048). Conclusion: This multicentre study demonstrates that Ki67 is an independent and reproducible prognostic factor in epithelioid but not in non-epithelioid MPM and suggests that induction chemotherapy decreases the proliferative capacity of MPM.

The complement component C5a is a potent inflammatory peptide, which may be involved in the pathogenesis of Chronic Obstructive Pulmonary Disease (COPD). We analysed the induced sputum and plasma of 28 patients with stable COPD, 12 healthy smokers and 7 non-smokers. In 13 of the patients with COPD, we also observed paired samples during acute exacerbation. The concentrations of C5a/C5a desArg and C3a/C3a desArg were measured using cytometric bead array. Both C5a and C3a concentrations in induced sputum of stable patients with COPD were significantly increased compared to the control groups of healthy smokers and non-smokers. In addition, there was a significant elevation in C5a values in exacerbation of COPD that was independent from the airway C3a levels. Airway C5a levels were negatively correlated with forced expiratory volume in first second (FEV1)% predicted and diffusing capacity of the lung (TLCO). Plasma C5a concentrations in patients with COPD were significantly higher than in healthy smokers, but no further significant systemic C5a elevation was detected with acute exacerbation of COPD. There was no important difference in local or systemic C5a concentrations between healthy smokers and non-smokers. These in vivo results clearly show that local and systemic C5a concentrations in COPD are elevated, and that the local, in contrast to systemic, C5a concentrations additionally increase in the acute exacerbation of COPD. It seems that the cigarette smoke is not related to C5a increase. The elevated local and systemic C5a levels, and additional individual local C5a increase during the exacerbation support the importance of C5a in COPD.

The florigen paradigm implies a universal flowering-inducing hormone that is common to all flowering plants. Recent work identified FT orthologues as originators of florigen and their polypeptides as the likely systemic agent. However, the developmental processes targeted by florigen remained unknown. Here we identify local balances between SINGLE FLOWER TRUSS (SFT), the tomato precursor of florigen, and SELF-PRUNING (SP), a potent SFT-dependent SFT inhibitor as prime targets of mobile florigen. The graft-transmissible impacts of florigen on organ-specific traits in perennial tomato show that in addition to import by shoot apical meristems, florigen is imported by organs in which SFT is already expressed. By modulating local SFT/SP balances, florigen confers differential flowering responses of primary and secondary apical meristems, regulates the reiterative growth and termination cycles typical of perennial plants, accelerates leaf maturation, and influences the complexity of compound leaves, the growth of stems and the formation of abscission zones. Florigen is thus established as a plant protein functioning as a general growth hormone. Developmental interactions and a phylogenetic analysis suggest that the SFT/SP regulatory hierarchy is a recent evolutionary innovation unique to flowering plants.

To evaluate the relationship between CD40/CD40L system and increased thrombogenesis in AF, and to test the effects of simvastatin treatment.In vitro study using human tissue, University Hospital (tertiary referral center). Experiments on right atrial segments obtained before the onset of cardiopulmonary bypass were done in either presence or absence of 5 μM simvastatin. Two groups of patients in either chronic atrial fibrillation or sinus rhythm at the time of cardiac surgery. The endocardial expression of CD40, the release of CD40L, and adhesion of platelets to endocardium. Additionally, the thickness of platelet aggregates and the platelet distribution on the endocardium were also evaluated.Atrial fibrillation was associated with a significant increase of endocardial CD40 expression (293.1 ± 55.1 pg/ml vs. 230.9 ± 53.3 pg/ml, p < 0.01), and platelet–endocardial adhesion compared with sinus rhythm atria (10.8 ± 2.2 vs. 5.2 ± 1.3 platelet CD41 AU p < 0.01). At immunofluorescence about 62% of fibrillating endocardium was covered by platelets, compared with 12% of not sinus rhythm atria. Addition of simvastatin significantly reduced CD40 expression as well as platelet adhesion to fibrillating atria; its efficacy was not reversed by the addition of mevalonic acid.Chronic atrial fibrillation acutely upregulates CD40 expression as well as platelet adhesion to the endocardium. Simvastatin is effective in modulating this expression, thus it may potentially contribute to reduce the risk of intra-atrial thrombus formation.

PURPOSE:Pleurodesis can relieve dyspnea in patients with malignant pleural effusions. We retrospectively compared the success rate of talc slurry instillation pleurodesis with thoracoscopic talc powder insufflation pleurodesis. PATIENTS AND METHODS:From 2000 to 2005, two methods of talc pleurodesis were performed in 71 patients with symptomatic massive malignant pleural effusions: a) through the pleural drain (24F), 50 ml of a slurry containing 4-5 g of Luzenac talc in saline with 20 ml 1% lidocaine were instilled. The drain was clamped for 1 h; b) insufflation of 3-5 g of talc powder was performed via videothoracoscope using local anaesthesia. The drain was left in the pleural space until the daily secretion of pleural fluid was under 100 ml. Pleurodesis was considered successful when the patient was without dyspnea and did not need pleural fluid evacuation and the pleural fluid did not re-accumulate in the 1st month after pleurodesis. RESULTS:The success rate of talc slurry pleurodesis was 78%(38/49). Excluding 8 patients who died in the first month, the success rate increased to 93% (38/41). Thoracoscopic pleurodesis was successful in 77% (17/22) of patients. Excluding one patient who died in the first month, the success rate increased to 81%(17/21) (intergroup difference non significant). Complications were observed in 41% (20/49). vs. 73% (16/22) of patients in the talc slurry group and thoracoscopic group, respectively (p=0.013). CONCLUSION:Pleurodesis with instillation of talc slurry and with insufflation of talc during thoracoscopy were equally successful in patients with massive malignant pleural effusions. However, thoracoscopic pleurodesis is accompanied with considerably more complications, rather as a result of the thoracoscopy itself and not as a consequence of pleurodesis.