Time course of ischemic and bleeding burden in consecutive patients undergoing transcatheter aortic valve replacement (FOCUS-ONE Registry).

BACKGROUND AND AIMS: Ischemic or bleeding events might occur after transcatheter aortic valve replacement (TAVR), with the potential to hamper clinical outcomes. This study aimed to characterize the average daily ischemic risks (ADIRs) and the average daily bleeding risks (ADBRs) over 1-year in all consecutive patients undergoing TAVR. METHODS: ADBR included all bleeding events according to VARC-2 definition, and ADIR included cardiovascular deaths, myocardial infarction and ischemic stroke. ADIRs and ADBRs were assessed within different timeframes post TAVR: acute (0-30 days), late (31-180 days), and very late (>181 days). Generalized estimating equations were used to test the least squares mean differences for the pairwise comparison of ADIRs and ADBRs. Our analysis was performed in the overall cohort and according to antithrombotic strategy (LT-OAC vs No LT-OAC). RESULTS: Ischemic burden was higher than bleeding burden, independently from the indication to LT-OAC, and in all timeframes examined. In the overall population, ADIRs were three-fold ADBRs (0.0467 [95% CI, 0.0431-0.0506] vs 0.0179 [95% CI, 0.0174-0.0185]; p < 0.001*). While ADIR was significantly higher in the acute phase, ADBR was relatively stable in all timeframes analysed. Of note, in LT-OAC population, OAC + SAPT group showed lower ischemic risk and higher bleeding events compared with OAC alone (ADIR: 0.0447 [95% CI: 0.0417-0.0477] vs 0.0642 [95% CI: 0.0557-0.0728]; p < 0.001*, ADBR 0.0395 [95% CI: 0.0381-0.0409] vs 0.0147 [95% CI: 0.0138-0.0156]; p < 0.001*). CONCLUSIONS: In patients undergoing TAVR Average daily risk fluctuates over time. However, ADIRs overcome ADBRs in all timeframes, especially in the acute phase and regardless of antithrombotic strategy adopted.

Rapid detection of Legionella spp in water samples by ScanVIT method: comparison of acid vs heat treatment.

BACKGROUND: A rapid detection of Legionella bacteria in water samples is crucial to minimize the risk of acquiring infections, especially in health care facilities. Different detection methods and different decontamination procedures have been reported to affect the recovery of Legionella spp. Our goal was to test the recovery of Legionella pneumophila and Legionella non-pneumophila species using a kit based on non-specific and species-specific probes to treat water samples after two different decontamination procedures. METHODS: The study was conducted with samples collected in the teaching hospital "Le Scotte" of Siena (Italy). Waters samples were analyzed by: i) ScanVIT method after treatment with acids; ii) ScanVIT method after heating; and iii) cultural standard method after heating. The results of the decontamination procedures and the detection methods were evaluated by comparing the number of Legionella-positive and -negative samples, and the recovery rates (CFU l-1) obtained by ScanVIT and the standard method. RESULTS: We find that ScanVIT method is highly sensitive with both decontamination treatments, yielding a higher recovery of L. pneumophila compared to the standard method. Conversely, ScanVIT associated with the acid-treatment yielded the highest recovery of L. non-pneumophila. CONCLUSIONS: The acid-treatment combined to the ScanVIT method increases the recovery of L. non-pneumophila in water samples compared to both ScanVIT associated with heat-treatment and standard culture method. Thus, this method may represent the best choice to detect L. non-pneumophila in water samples and reduce the risk of infection due to underestimation of Legionella loads.

Synchrotron FTIR and Raman spectroscopy provide unique spectral fingerprints for Arabidopsis floral stem vascular tissues.

Cell walls are highly complex structures that are modified during plant growth and development. For example, the development of phloem and xylem vascular cells, which participate in the transport of sugars and water as well as providing support, can be influenced by cell-specific wall composition. Here, we used synchrotron radiation-based Fourier-transform infrared (SR-FTIR) and Raman spectroscopy to analyse the cell wall composition of floral stem vascular tissues of wild-type Arabidopsis and the double-mutant sweet11-1 sweet12-1, which has impaired sugar transport. The SR-FTIR spectra showed that in addition to modified xylem cell wall composition, phloem cell walls in the double-mutant line were characterized by modified hemicellulose composition. Combining Raman spectroscopy with a classification and regression tree (CART) method identified combinations of Raman shifts that could distinguish xylem vessels and fibers. In addition, the disruption of the SWEET11 and SWEET12 genes impacted on xylem wall composition in a cell-specific manner, with changes in hemicelluloses and cellulose observed at the xylem vessel interface. These results suggest that the facilitated transport of sugars by transporters that exist between vascular parenchyma cells and conducting cells is important in ensuring correct phloem and xylem cell wall composition.

Correlation between benzene and testosterone in workers exposed to urban pollution.

AIM: Many studies have examined the effects of benzene on testosterone. The purpose of this study was to evaluate the possible correlation between the blood levels of benzene and the levels of testosterone. MATERIALS AND METHODS: The study involved a group of 148 subjects. For every worker have been made out a blood sample for the evaluation of benzene and testosterone levels and an urine analysis for the evaluation of the levels of trans, trans-muconic acid and S-phenylmercapturic acid. We estimated the Pearson correlation coefficient between the variables in the sample and the urinary metabolites, age, length of service, gender, BMI. For the analysis of the major confounding factors it was performed a multiple linear regression. RESULTS: The Pearson correlation coefficiet showed: 1. a significant inverse correlation between the S-phenyl mercapturic acid and free testosterone; 2. a significant direct correlation between trans-trans muconic acid and BMI. After dividing the sample according to the median of blood benzene (161.0 ng / L), Pearson correlation coefficient showed a significant inverse correlation between the S-phenyl mercapturic acid and free testosterone in the group with values below this median. CONCLUSIONS: Our results, to be considered preliminary, suggest that occupational exposure to low levels of benzene, present in urban pollution, affect the blood levels of testosterone. These results need to be confirmed in future studies, with the eventual possibility of including more specific fertility tests.

Geometrical modified nesbit corporoplasty to correct different types of penile curvature: description of the surgical procedure based on geometrical principles and long-term results.

We present the use of a modified corporoplasty, based on geometrical principles, to determine the exact site for the incision in the tunica or plaque and the exact amount of albuginea for overlaying to correct with extreme precision the different types of congenital or acquired penile curvature due to Peyronie's disease. To describe our experience with a new surgical procedure for the enhancement of penile curvature avoiding any overcorrection or undercorrection. Between March 2004 and April 2013, a total of 74 patients underwent the geometrical modified corporoplasty. All patients had congenital curvature until 90° or acquired stable penile curvature 'less' than 60°, that made sexual intercourse very difficult or impossible, normal erectile function, absence of hourglass or hinge effect. Preoperative testing included a physical examination, 3 photographs (frontal, dorsal and lateral) of penis during erection, a 10 mcg PGE1-induced erection and Doppler ultrasound, administration of the International Index of Erectile Function (IIEF-15) questionnaire. A follow-up with postoperative evaluation at 12 weeks, 12 and 24 months, included the same preoperative testing. Satisfaction rates were better assessed with the use of validated questionnaire such as the International Erectile Dysfunction Inventory of the Treatment Satisfaction (EDITS). Statistical analysis with Student's t-test was performed using commercially available, personal computer software. A total of 25 patients had congenital penile curvature with a mean deviation of 46.8° (range 40-90), another 49 patients had Peyronie's disease with a mean deviation of 58.4 (range 45-60). No major complications were reported. Postoperative correction of the curvature was achieved in all patients (100%). Neither undercorrection nor overcorrection were recorded. No significant relapse (curvature>15°) occurred in our patients. Shortening of the penis was reported by 74% but did not influence the high overall satisfaction of 92% (patients completely satisfied with their sexual life). The erectile function was analyzed in both groups, Student's t-test showed a significant improvement in erectile function, preoperative average IIEF-15 scores were 17.43±4.67, whereas postoperatively it was 22.57±4.83 (P=0.001). This geometrical modified Nesbit corporoplasty is a valid therapy which allows penile straightening. The geometric principles make the technique reproducible in multicentre studies.

Microstructural, mechanical, and histological evaluation of modified alginate-based scaffolds.

Scaffolds are three-dimensional structures used for tissue regeneration being the base in tissue engineering. These scaffolds are obtained from natural and/or synthetic polymers and they should satisfy some specific requirements such as biocompatibility, suitable mechanical, and microstructural properties to favor cellular adhesion and neovascularization. This work shows a preclinic study about the production of low and medium molecular weight alginate through the use of calcium salts (calcium glutamate). The results showed prove that better structures, distribution, and pore sizes as well as better mechanical properties correspond to medium molecular weight alginate and higher calcium salts concentration. This type of scaffold, after muscular cells cultivation, has been proved as an excellent material for muscle growth. The histopathological analysis shows a low inflammatory response, without a foreign body reaction, suitable neovascularization and good fibroblasts incorporation. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 3107-3114, 2016.

[Evaluation of liver function between indoor and outdoor workers: preliminary results].

INTRODUCTION: The aim of our study is to compare liver damage in "outdoor" environment technicians, a category occupationally exposed, and in "indoor" workers. MATERIALS AND METHODS: We studied 142 male technicians of the environment exposed to urban pollution and 142 male "indoor" workers not exposed. We compared mean and standard deviation of the following liver parameters: glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), gamma-glutamyl-traspeptidasi (γGT) and alkaline phosphatase (PHA), total bilirubin (TB) and direct (DB). We made the two groups comparable for age, length of service, BMI, alcohol consumption and smoking habits, and excluded the workers who presented confounding factors. RESULTS: We found statistically significant differences about the levels of γGT, PHA, GPT and albumin between the "outdoor" workers exposed and the "indoor" control group. In the outdoor group we observed statistically significant values, GPT (51.8 ± 30.6 I.U./l vs. 30 ± 22.3 I.U./l; p = 0.000), γ-GT (42.2 ± 29.4 I.U./l vs. 22.4 ± 20.7 I.U./l; p = 0.000) and PHA (75.7 ± 20.6 I.U./l vs. 59.1 ± 19.6 I.U./l; p= 0.000) compared to the unexposed group. No statistically significant difference emerged between the averages for the values of GOT (25.3 ± 20.7 I.U./l vs. 26 ± 17.7 I.U./l; p = 0.736) in two groups. CONCLUSIONS: It clearly emerges that the contaminants may alter the values of liver tests after prolonged exposure.

Combined microscopy and molecular analyses show phloem occlusions and cell wall modifications in tomato leaves in response to 'Candidatus Phytoplasma solani'.

Callose deposition, phloem-protein conformational changes and cell wall thickening are calcium-mediated occlusions occurring in the plant sieve elements in response to different biotic and abiotic stresses. However, the significance of these structures in plant-phytoplasma interactions requires in-depth investigations. We adopted a novel integrated approach, based on the combined use of microscopic and molecular analyses, to investigate the structural modifications induced in tomato leaf tissues in presence of phytoplasmas, focusing on vascular bundles and on the occlusion structures. Phloem hyperplasia and string-like arrangement of xylem vessels were found in infected vascular tissue. The diverse occlusion structures were differentially modulated in the phloem in response to phytoplasma infection. Callose amount was higher in midribs from infected plants than in healthy ones. Callose was observed at sieve plates but not at pore-plasmodesma units. A putative callose synthase gene encoding a protein with high similarity to Arabidopsis CalS7, responsible for callose deposition at sieve plates, was upregulated in symptomatic leaves, indicating a modulation in the response to stolbur infection. P-proteins showed configuration changes in infected sieve elements, exhibiting condensation of the filaments. The transcripts for a putative P-protein 2 and a sieve element occlusion-related protein were localized in the phloem but only the first one was modulated in the infected tissues.

An Experimental Study on the Use of Calcium Alginate to Heal Colonic Anastomoses.

BACKGROUND: Anastomotic leak is considered the major complication following abdominal surgery. In recent years, the use of a variety of sealing materials for the prevention of leaks has been analyzed. Different biomaterials have been employed as scaffolds to favour tissue repair and regeneration. Among these materials we must mention alginate, a natural polymer with different applications as temporary supporting matrix. The aim of the present study is to evaluate the behavior of both alginate-impregnated sutures and lyophilized alginate sponges in the healing process of colonic anastomes using an experimental animal model. MATERIAL AND METHODS: A preliminary study was undertaken to select the adequate scaffold. Animals (n = 45) were distributed into three groups: control (colonic anastomosis using non-continuous 5-0 Polyglactin 910 suture), suture (colonic anastomosis using suture impregnated with alginate gel at 4%) and sponge (colonic anastomosis using suture reinforced with lyophilized alginate sponge). The macroscopic and histological variables were assessed at 4, 8 and 12 days after surgical intervention. RESULTS: No statistically significant differences have been observed between the groups during the analysis of macroscopic variables. Animals with sponge implantation showed a greater degree of epithelial reepithalization, less acute and chronic inflammation and greater collagen deposit. CONCLUSIONS: The use of lyophilized alginate sponges to reinforce colonic anastomoses in an animal model reduces inflammation and promotes the earlier formation of greater collagen deposits without increasing the number of adhesions or the incidence of stenosis.

Adjusted indirect comparison of new oral anticoagulants for stroke prevention in atrial fibrillation.

BACKGROUND: Vit-K antagonists are the therapy of choice to prevent thromboembolic events due to atrial fibrillation since many years. New oral anticoagulants (NOA) showed encouraging results vs. warfarin but there are no data directly comparing different NOA. We performed an adjusted indirect meta-analysis. METHODS: Randomized controlled trials (RCTs) were searched. Efficacy end points were the cumulative rate of thomboembolic stroke (TES) and systemic embolism (SE). Main safety end point was the rate of hemorrhagic stroke (HS). RESULTS: Three RCTs (50578 patients) were included. Overall, NOA were comparable to warfarin according to the cumulative risk of TES and SE, as well as for TES alone. NOA were associated with a reduced rate of SE [OR 0.64 (0.44, 0.94], P=0.02]. Compared to warfarin, NOA were associated with a significantly reduced risk of HS [OR 0.43 (0.34, 0.55), P<0.001, NNT to avoid a HS 153] and all cause death [OR 0.90 [0.84, 0.96], P=0.03, NNT to save one fatality 43]. Head to head comparison showed that in terms of cumulative rate of TES/SE, as well as of TES, none of the NOA was significantly superior to the others (all Ps>0.05). Rivaroxaban showed superiority in the prevention of SE. Dabigatran 150 mg/twice daily was associated with the largest reduction in the risk of HS vs. warfarin and vs. other NOA. Overall mortality was quite comparable across NOA. CONCLUSION: Overall superiority of NOA over warfarin is largely influenced by the reduction of HS. Dabigatran 150 mg/twice daily seems to have the best risk/benefit profile.

Apoptosis and autoimmunity induced by clodronate in systemic lupus erythematosus mononuclear circulating cells.

The aim of this study is to evaluate the effect of clodronate on apoptosis of human systemic lupus erythematosus circulating mononuclear cells and to analyze possible correlations with changes in autoantibody production in vitro. Lympho-monocytes from 20 SLE patients were isolated and incubated with or without addition of 1 microM clodronate for 72 hours. Apoptosis and release of genomic material was assessed by immunofluorescent detection of cleaved caspase-3 and by Cell-Death-Detection ELISAPLUS kit (Roche). Anti-Nucleosome IgG and anti-dsDNA IgM and IgG autoantibody levels were determined in supernatants by commercially available ELISA kits. Clodronate induced apoptosis in monocytes as confirmed by cleaved caspase-3 immunostaining and by quantification of cleaved nucleosome in the supernatants (treated 0.22+/-0.05 O.D. vs untreated 0.09+/-0.04 O.D.; P less than 0.001). This finding was coupled with a significant increasing in supernatants of IgG anti-Nucleosome (treated 6.5+/-1.1 vs untreated 5.5+/-0.6 IU/mL; p=0.001) and IgM (treated 3.0+/-1.3 vs 2.2+/-0.9 IU/mL; p=0.02) and IgG (treated 4.0+/-1.8 vs untreated 2.8+/-1.5 IU/mL; p=0.02) anti-dsDNA autoantibody levels. Our findings stressed the pro-apoptotic activity of clodronate, as well as its potential autoimmunity induction in SLE mononuclear circulating cells. Clinical studies could clarify the role of bisphosphonates on autoantibody production and worsening of disease activity.

Percutaneous coronary interventions in cardiac allograft vasculopathy: a single-center experience.

OBJECTIVE: Cardiac allograft vasculopathy represents an accelerated form of obstructive coronary disease. It is the main cause of late death following heart transplantation. Percutaneous coronary intervention is considered a palliative procedure due to high restenosis rates. The aim of this study was to review our experience with percutaneous coronary interventions using stents in cardiac transplant recipients. METHODS: The present analysis included all primary adult heart transplanted patients who had been discharged from the hospital after transplantation, had a clinical follow-up of 12 months and underwent percutaneous coronary intervention (PCI). RESULTS: Seventy heart transplanted patients underwent percutaneous revascularization. Our analysis comprised 85 first-vessel procedures resulting in treatment of 135 lesions. The mean time from heart transplantation to first intervention was 9.3 +/- 4.8 years. Primary success was obtained in 96% lesions; at least 1 recurrent stenosis event occurred in 16 patients with primarily successful PCI. Lesions treated with drug-eluting stents experienced recurrent stenosis in 16% of cases. During a mean follow-up after PCI of 45.2 +/- 41.7 months, 27 deaths (19 cardiac) and 1 late re-transplantation occurred after PCI. CONCLUSION: In cardiac transplant recipients, percutaneous coronary intervention with stents can be performed safely with high rates of primary success. Restenosis rates were higher compared with coronary interventions in native coronary arteries. Drug-eluting stents seemed to favorably impact restenosis compared with bare-metal stents. The clinical benefit from percutaneous coronary intervention may be reduced due to disease progression in untreated coronary segments.

Protective effect of ferulic acid ethyl ester against oxidative stress mediated by UVB irradiation in human epidermal melanocytes.

UV solar radiation is the major environmental risk factor for malignant melanoma. A great effort is currently posed on the search of new compounds able to prevent or reduce UV-mediated cell damage. Ferulic acid is a natural compound recently included in the formulation of solar protecting dermatological products. The purpose of the present work was to assess whether its ethyl ester derivative, FAEE, could protect skin melanocytes from UV-induced oxidative stress and cell damage. Experiments on human melanocytes irradiated with UVB showed that FAEE treatment reduced the generation of ROS, with a net decrease of protein oxidation. FAEE treatment was accompanied by an induction of HSP70 and heme oxygenase, by a marked suppression of PARP activation and a significant suppression of apoptosis. Moreover FAEE prevented iNOS induction, thus suppressing the secondary generation of NO-derived oxidizing agents. FAEE may represent a potentially effective pharmacological approach to reduce UV radiation-induced skin damage.

Telomere length identifies two different prognostic subgroups among VH-unmutated B-cell chronic lymphocytic leukemia patients.

Some evidences suggest that telomere restriction fragment length (TRF-L) is an effective indicator of histopathogenesis in B-cell tumors. As histopathogenesis is relevant for B-cell chronic lymphocytic leukemia (B-CLL) prognosis, TRF-L was assessed by Southern blot in 201 patients and compared to variable immunoglobulin heave chain gene mutational status (VH-MS) and to other known prognostic features. Overall survival (OS), time to first treatment (TTFT) and progression-free survival (PFS) were evaluated. Our results indicate the following: (1) TRF-L is heterogeneous among B-CLL patients (median 6014 bp, range 1465-16 762); (2) TRF-L correlates to VH-MS (r(2)=0.1994, P<0.0001) with VH-mutated patients showing long and VH-unmutated short telomeres; however, 41% of VH-unmutated and 5% of VH-mutated patients did not show this correlation and were thus defined as 'discordant'; (3) TRF-L effectively predicts outcome in terms of TTFT, PFS and OS; (4) VH-unmutated discordant patients have a better clinical outcome than VH-unmutated concordant patients (OS P<0.01, PFS P<0.05) and similar to that of VH-mutated patients (OS, PFS P=NS). Compared to VH-unmutated concordant patients, VH-unmutated discordant patients showed no peculiarity in their immunoglobulin rearrangement nor in their flow cytometry or fluorescence in situ hybridization profile. In conclusion, TRF-L can be helpful to refine prognostication of B-CLL patients, particularly those with a VH-unmutated immunoglobulin sequence.

Prolonged survival and low incidence of late toxic sequelae in advanced follicular lymphoma treated with a TBI-free autografting program: updated results of the multicenter consecutive GITMO trial.

This study provides an updated report of the consecutive multicenter Gruppo Italiano Trapianto Midollo Osseo trial employing an intensified, purging-free, total body irradiation-free, high-dose sequential chemotherapy schedule with peripheral blood stem cell autograft (i-HDS) in advanced-stage follicular lymphoma (FL). Special interest has been devoted to late toxicities and outcome in terms of molecular status. Ninety-two untreated FL patients aged

Marked telomere shortening in mobilized peripheral blood progenitor cells (PBPC) following two tightly spaced high-dose chemotherapy courses with G-CSF.

The purpose of the study was to compare telomere length (TL) in peripheral blood progenitor cells (PBPC) collected after two tightly spaced high-dose (hd) chemotherapy courses. We assessed 37 previously untreated lymphoma patients undergoing a hd-chemotherapy program with autografting. They sequentially received hd-cyclophosphamide (CY) and hd-Ara-C, both followed by PBPC harvesting. Both post-CY and post-Ara-C harvests were assessed for TL by Southern blot analysis. In 12 patients, the assay was also performed on purified CD34+ cells. All patients displayed high PBPC mobilization following both hd-CY and hd-Ara-C. In all but one patient, TL was shorter in PBPC collected after Ara-C compared to CY: 7226bp (range: 4135-9852) vs 8282 bp (range 4895-14860) (P < 0.0001). This result was confirmed on CD34+ cells. Platelet recovery in patients receiving post-Ara-C PBPC was significantly slower compared to those receiving post-CY PBPC. In conclusion, (i) administration of tightly spaced hd-chemotherapy courses induces marked telomere shortening on harvested PBPC; (ii) engraftment kinetics seem slower, with delayed platelet recovery, in patients autografted with PBPC suffering marked TL erosion; (iii) long-term follow-up is required to verify whether PBPC with shortened telomeres display defective engraftment stability and/or risk of secondary leukemia; (iv) TL evaluation is advisable whenever new mobilization procedures are developed.

Red blood cell transfusion does not increase oxygen consumption in critically ill septic patients.

BACKGROUND: Red blood cell (RBC) transfusion is commonly used to increase oxygen transport in patients with sepsis. However it does not consistently increase oxygen uptake at either the whole-body level, as calculated by the Fick method, or within individual organs, as assessed by gastric intra-mucosal pH. AIM: This study evaluates the hemodynamic and oxygen utilization effects of hemoglobin infusion on critically ill septic patients. METHODS: Fifteen septic patients undergoing mechanical ventilation whose hemoglobin was <10 g% were eligible. Ten patients (APACHE II: 25.5 +/- 7.6) received an infusion of 1 unit of packed RBC over 1 h while sedated and paralyzed. The remaining five control patients (APACHE II: 24.3 +/- 6.0) received a 5% albumin solution (500 ml) over 1 h. Hemodynamic data, gastric tonometry and calorimetry were obtained prior to and immediately after RBC transfusion or 5% albumin infusion. RESULTS: Transfusion of RBC was associated with an improvement in left ventricular systolic work index (38.6 +/- 12.6 to 41.1 +/- 13.0 g/min/m2; P = 0.04). In the control group there was no significant change in the left ventricular systolic work index (37.2 +/- 14.3 to 42.2 +/- 18.9 g/min/m2). An increase in pulmonary vascular resistance index (203 +/- 58 to 238 +/- 49 dyne/cm5/m2; P = 0.04) was also observed, while no change was produced by colloid infusion (237 +/- 87.8 to 226.4 +/- 57.8 dyne/cm5/m2). Oxygen utilization did not increase either by Fick equation or by indirect calorimetry in either group. Gastric intramucosal pH increased only in the control group but did not reach statistical significance. CONCLUSION: Hemoglobin increase does not improve either global or regional oxygen utilization in anemic septic patients. Furthermore, RBC transfusion may hamper right ventricular ejection by increasing the pulmonary vascular resistance index.