Intense therapy in patients with locally advanced esophageal cancer beyond hope for surgical cure: a prospective, multicenter phase II trial of the Swiss Group for Clinical Cancer Research (SAKK 76/02)

There is no standard treatment for patients with locally advanced esophageal carcinoma without systemic metastasis in whom surgery is no longer considered a reasonable option.

Assessment of right ventricular systolic function: Comparison between cardiac magnetic resonance derived ejection fraction and pulsed-wave tissue Doppler imaging of the tricuspid annulus

Systolic right ventricular (RV) function is an important predictor in the course of various congenital and acquired heart diseases. Its practical determination by echocardiography remains challenging. We compared routine assessment of lateral tricuspid annular systolic motion velocity (TV(lat), cm/s) using pulsed-wave tissue Doppler imaging from the apical 4-chamber view with cardiac magnetic resonance (CMR) as reference method.

Clinical outcome of high-risk patients with severe aortic stenosis and reduced left ventricular ejection fraction undergoing medical treatment or TAVI

Introduction Reduced left ventricular function in patients with severe symptomatic valvular aortic stenosis is associated with impaired clinical outcome in patients undergoing surgical aortic valve replacement (SAVR). Transcatheter Aortic Valve Implantation (TAVI) has been shown non-inferior to SAVR in high-risk patients with respect to mortality and may result in faster left ventricular recovery. Methods We investigated clinical outcomes of high-risk patients with severe aortic stenosis undergoing medical treatment (n = 71) or TAVI (n = 256) stratified by left ventricular ejection fraction (LVEF) in a prospective single center registry. Results Twenty-five patients (35%) among the medical cohort were found to have an LVEF≤30% (mean 26.7±4.1%) and 37 patients (14%) among the TAVI patients (mean 25.2±4.4%). Estimated peri-interventional risk as assessed by logistic EuroSCORE was significantly higher in patients with severely impaired LVEF as compared to patients with LVEF>30% (medical/TAVI 38.5±13.8%/40.6±16.4% versus medical/TAVI 22.5±10.8%/22.1±12.8%, p <0.001). In patients undergoing TAVI, there was no significant difference in the combined endpoint of death, myocardial infarction, major stroke, life-threatening bleeding, major access-site complications, valvular re-intervention, or renal failure at 30 days between the two groups (21.0% versus 27.0%, p = 0.40). After TAVI, patients with LVEF≤30% experienced a rapid improvement in LVEF (from 25±4% to 34±10% at discharge, p = 0.002) associated with improved NYHA functional class at 30 days (decrease ≥1 NYHA class in 95%). During long-term follow-up no difference in survival was observed in patients undergoing TAVI irrespective of baseline LVEF (p = 0.29), whereas there was a significantly higher mortality in medically treated patients with severely reduced LVEF (log rank p = 0.001). Conclusion TAVI in patients with severely reduced left ventricular function may be performed safely and is associated with rapid recovery of systolic left ventricular function and heart failure symptoms.

Value of age, creatinine, and ejection fraction (ACEF score) in assessing risk in patients undergoing percutaneous coronary interventions in the 'All-Comers' LEADERS trial

Background— The age, creatinine, and ejection fraction (ACEF) score (age/left ventricular ejection fraction+1 if creatinine >2.0 mg/dL) has been established as an effective predictor of clinical outcomes in patients undergoing elective coronary artery bypass surgery; however, its utility in “all-comer” patients undergoing percutaneous coronary intervention is yet unexplored. Methods and Results— The ACEF score was calculated for 1208 of the 1707 patients enrolled in the LEADERS trial. Post hoc analysis was performed by stratifying clinical outcomes at the 1-year follow-up according to ACEF score tertiles: ACEFlow ≤1.0225, 1.0225< ACEFmid ≤1.277, and ACEFhigh >1.277. At 1-year follow-up, there was a significantly lower number of patients with major adverse cardiac event–free survival in the highest tertile of the ACEF score (ACEFlow=92.1%, ACEFmid=89.5%, and ACEFhigh=86.1%; P=0.0218). Cardiac death was less frequent in ACEFlow than in ACEFmid and ACEFhigh (0.7% vs 2.2% vs 4.5%; hazard ratio=2.22, P=0.002) patients. Rates of myocardial infarction were significantly higher in patients with a high ACEF score (6.7% for ACEFhigh vs 5.2% for ACEFmid and 2.5% for ACEFlow; hazard ratio=1.6, P=0.006). Clinically driven target-vessel revascularization also tended to be higher in the ACEFhigh group, but the difference among the 3 groups did not reach statistical significance. The rate of composite definite, possible, and probable stent thrombosis was also higher in the ACEFhigh group (ACEFlow=1.2%, ACEFmid=3.5%, and ACEFhigh=6.2%; hazard ratio=2.04, P<0.001). Conclusions— ACEF score may be a simple way to stratify risk of events in patients treated with percutaneous coronary intervention with respect to mortality and risk of myocardial infarction.

Fluctuation phenotyping based on daily fraction of exhaled nitric oxide values in asthmatic children

Fraction of exhaled nitric oxide (Feno), a marker of airway inflammation, has been proposed to be useful for asthma management, but conclusions are inconsistent. This might be due to the failure of mean statistics to characterize individual variability in Feno values, which is possibly a better indicator of asthma control than single measurements.

Depth of cure of resin composites: is the ISO 4049 method suitable for bulk fill materials?

To evaluate if depth of cure D(ISO) determined by the ISO 4049 method is accurately reflected with bulk fill materials when compared to depth of cure D(new) determined by Vickers microhardness profiles.

Effects of right ventricular pacing on left ventricular ejection fraction in a pacemaker clinic

The aim of this study was to evaluate whether a change of left ventricular ejection fraction (LVEF) depending on percentage of right ventricular pacing is found in a real-life setting of a pacemaker clinic.

Importance of the sampled milk fraction for the prediction of total quarter somatic cell count

This study investigated the changes in somatic cell counts (SCC) in different fractions of milk, with special emphasis on the foremilk and cisternal milk fractions. Therefore, in Experiment 1, quarter milk samples were defined as strict foremilk (F), cisternal milk (C), first 400 g of alveolar milk (A1), and the remaining alveolar milk (A2). Experiment 2 included 6 foremilk fractions (F1 to F6), consisting of one hand-stripped milk jet each, and the remaining cisternal milk plus the entire alveolar milk (RM). In Experiment 1, changes during milking indicated the importance of the sampled milk fraction for measuring SCC because the decrease in the first 3 fractions (F, C, and A1) was enormous in milk with high total quarter SCC. The decline in SCC from F to C was 50% and was 80% from C to A1. Total quarter SCC presented a value of approximately 20% of SCC in F or 35% of SCC in C. Changes in milk with low or very low SCC were marginal during milking. Fractions F and C showed significant differences in SCC among different total SCC concentrations. These differences disappeared with the alveolar fractions A1 and A2. In Experiment 2, a more detailed investigation of foremilk fractions supported the findings of Experiment 1. A significant decline in the foremilk fractions even of F1 to F6 was observed in high-SCC milk at concentrations >350 x 10(3) cells/mL. Although one of these foremilk fractions presented only 0.1 to 0.2% of the total milk, the SCC was 2- to 3-fold greater than the total quarter milk SCC. Because the trait of interest (SCC) was measured directly by using the DeLaval cell counter (DCC), the quality of measurement was tested. Statistically interesting factors (repeatability, recovery rate, and potential matrix effects of milk) proved that the DCC is a useful tool for identifying the SCC of milk samples, and thus of grading udder health status. Generally, the DCC provides reliable results, but one must consider that SCC even in strict foremilk can differ dramatically from SCC in the total cisternal fraction, and thus also from SCC in the alveolar fraction.

Characterization of the fetuin-binding fraction of Neospora caninum tachyzoites and its potential involvement in host-parasite interactions

Terminal sialic acid residues on surface-associated glycoconjugates mediate host cell interactions of many pathogens. Addition of sialic acid-rich fetuin enhanced, and the presence of the sialidiase inhibitor 2-deoxy-2,3-dehydro-N-acetylneuraminic acid reduced, the physical interaction of Neospora caninum tachyzoites and bradyzoites with Vero cell monolayers. Thus, Neospora extracts were subjected to fetuin-agarose affinity chromatography in order to isolate components potentially interacting with sialic acid residues. SDS-PAGE and silver staining of the fetuin binding fraction revealed the presence of a single protein band of approximately 65 kDa, subsequently named NcFBP (Neospora caninum fetuin-binding protein), which was localized at the apical tip of the tachyzoites and was continuously released into the surrounding medium in a temperature-independent manner. NcFBP readily interacted with Vero cells and bound to chondroitin sulfate A and C, and anti-NcFBP antibodies interfered in tachyzoite adhesion to host cell monolayers. In additon, analysis of the fetuin binding fraction by gelatin substrate zymography was performed, and demonstrated the presence of two bands of 96 and 140 kDa exhibiting metalloprotease-activity. The metalloprotease activity readily degraded glycosylated proteins such as fetuin and bovine immunoglobulin G heavy chain, whereas non-glycosylated proteins such as bovine serum albumin and immunoglobulin G light chain were not affected. These findings suggest that the fetuin-binding fraction of Neospora caninum tachyzoites contains components that could be potentially involved in host-parasite interactions.

Prediction of arrhythmic events after myocardial infarction based on signal-averaged electrocardiogram and ejection fraction

Trials on implantable cardioverter-defibrillators (ICD) for patients after acute myocardial infarction (AMI) have highlighted the need for risk assessment of arrhythmic events (AE). The aim of this study was to evaluate risk predictors based on a novel approach of interpreting signal-averaged electrocardiogram (SAECG) and ejection fraction (EF).

Self-reactivity in the dimeric intravenous immunoglobulin fraction

Therapeutic intravenous immunoglobulin (IVIg) preparations contain antibodies reflecting the cumulative antigen experience of the donor population. IVIg contains variable amounts of monomeric and dimeric IgG, but there is little information available on their comparative antibody specificities. We have isolated highly purified fractions of monomeric and dimeric IgG by size-exclusion chromatography. Following treatment of all fractions at pH4, analyses by immunodot and immunocytology on human cell lines showed a preferential recognition of autoantigens in the dimeric IgG fraction. Investigation of the HEp-2 cytoplasmic proteome by 2D-PAGE, Western blot, and subsequent identification of IVIg reactive spots by mass spectrometry (LC-MS/MS) showed that IVIg recognized only a restricted set of the total proteins. Similar experiments showed that more antigens were recognized by the dimeric IgG fraction, especially when the dissociated dimer fraction was used, as compared to its monomeric counterpart. These observations are consistent with idiotype-anti-idiotype masking of auto-specific Abs in the dimeric fraction of IVIg.