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Polluted air streams can be purified using biological treatments such as biotrickling filtration, which is one of the most widely accepted techniques successfully tuned to treat a wide variety of exhausted gaseous streams coming from a series of industrial sectors such as food processing, flavor manufacturers, rendering, and composting. Since the degradation of a pollutant occurs at standard pressure and temperature, biotrickling filtration, whether compared with other more energy-demanding chemical-physical processes of abatement (such as scrubbing, catalytic oxidation, regenerative adsorption, incineration, advanced oxidation processes, etc.), represents a very high energy-efficient technology. Moreover, as an additional advantage, biodegradation offers the possibility of a complete mineralization of the polluting agents. In this work, biotrickling filtration has been considered in order to explore its efficiency with respect to the abatement of ammonia (which is a highly water-soluble compound). Moreover, a complete mathematical model has been developed in order to describe the dynamics of both absorption and biological activities which are the two dominant phenomena occurring into these systems. The results obtained in this work have shown that the absorption phenomenon is very important in order to define the global removal efficiency of ammonia from the gaseous stream (particularly, 44% of the ammonia is abated by water absorption). Moreover, it has been demonstrated (through the comparison between experimental results and theoretical simulations) that the action of bacteria, which enhance the rate of ammonia transfer to the liquid phase, can be modeled through a simple Michaelis-Menten relationship.

Competing Interests: Competing interests: None

A new deterministic model for the calculation of the specific denitrification rate (SDNR), useful for the design of pre-denitrification reactors, was tested on eight full-scale activated sludge plants. The model represents the SDNR at 20°C (SDNR 20°C ) as a function of the sludge loading in the denitrification reactor (F:M DEN ) and the residual dissolved oxygen in the denitrification reactor (DO DEN ). The results proved the ability of the model in calculating the SDNR 20°C . The model shows a lower degree of adaptability for small-sized plants. SDNR 20°C proved to have a strong sensitivity to DO DEN , mainly in correspondence with low DO concentrations (less than 2 mg L -1 ). The sensitivity decreases at greater DO values, but with a progressively less marked gradient, up to becoming weak only at DO concentrations greater than 0.4-0.5 mg L -1 , which are rarely found in full-scale plants. DO concentrations measured in real-scale facilities are mostly in the range 0.2-0.4 mg L -1 . These concentrations cause adverse effects on the kinetics of nitrogen removal, and consequently on the denitrification performance. Thus, minimizing DO in the pre-denitrification reactor is relevant. The sensitivity of SDNR 20°C to F:M DEN was less important, as it is characterized by a growing linear behaviour with a low slope.

We present our observational study on 40 patients treated with the medical device containing sodium hyaluronic acid and magnesium alginate, performing a lubricating and hydrating action. This device is in the form of a gel, with topical action to contrast gastroesophageal reflux and to exert a mechanical role of protection of the mucosal tissues (mouth-pharyngo-esophageal mucosa and gastric mucose.). Forty patients were recruited aged between 22- and 72-years-old with painful dyspeptic Gastro Esophageal Reflux Disease (GERD) symptomatology in acute or in clinical phase (25 patients) and with pharyngolaryngo- tracheal symptomatology (15 patients). Patients were divided into two clinical groups: Group A was treated with the medical device, while Group B with conventional treatments without the medical device. Subjects of both groups were also treated with proton pump inhibitors (PPIs). Follow-up was at 10, 20 and 30 days and patients were evaluated for reduction of their subjective symptoms, reduction of symptomatic and occasional therapies, reduction of inflammatory process or disappearance of epithelial lesions of the examined mucosa, healing process. The reduction of subjective symptoms was observed at 10 days in the patient with food bolus (disappearance after 5 days) and in patients with a reduction of 70%. A relevant reduction in the use of symptomatic drugs was noted. Our data are relevant considering symptom relief (heartburn, reflux and dyspepsia). New scenarios for the treatment of inflammatory diseases of the digestive and respiratory tract mucosa are at the horizon. Interdisciplinary translational research brings to the development of novel medical devices (as the one described in this study) with a high safety profile, and extremely active on the inflammation-repair-regeneration complex of different tissues and organs.

Background: In European countries, it is difficult for local health organizations to determine the resources allocated to different hospitals for breast cancer. The aim of the current study was to examine the costs of breast cancer during the different phases of the diagnostictherapeutic sequence based on real world data., Methods: To identify breast cancer cases diagnosed between 2007 and 2011, we used the cancer registry of the Agency for Health Protection of the Province of Milan (3.2 million inhabitants). A generalized linear model controlling for patient age, cancer stage and Charlson co-morbidity index was used to calculate the adjusted mean costs for each hospital and for each study phase. Regression analyses were based on dependent variables of individual costs (diagnosis, treatment, follow-up and total cost were logtransformed. The following independent variables were included as covariates: age at diagnosis, hospital volume, stage, job category, educational level, marital status, comorbidities, deprivation index. Total and mean costs were computed for several variables and for each phase. On average for each subject, the costs were collected over 2.5 years., Results: A total of 12,580 breast cancer cases were studied. The mean cost of diagnosis was €414, the mean cost of treatment was €8,780, the mean overall cost of follow-up was approximately €2,351, and the mean total direct medical cost was €10,970. The age of the patients, stage of tumor and employment level of the patient were significantly correlated with the variability of the costs. The highest variability in costs was observed for the follow-up costs, in which 38% of hospitals fell outside the 95% confidence interval. In the overspending-hospitals, patients received an intensive follow-up regimen with scintigraphy and thoracic CAT (computerized axial tomography)., Conclusions: In this study, which represents the first population-level study of its kind in Italy, we estimated all direct medical costs for the 6-month period before the diagnosis of breast cancer and the first two years after diagnosis. Patients were identified from the local cancer registry. The analysis offers insight into the utilization of resources incurred by one major area of interest of cancer care in Italy.

Groundwater pollution by municipal solid waste (MSW) landfill leachate is a global concern. Stripping towers are one of the most implemented techniques for the removal of ammonia pollution. This study presents a predictive computational model to estimate calcium carbonate precipitation in ammonia stripping towers. The model considers the Ca 2+ super-saturation condition due to the water pH, temperature and salinity. The results have been validated through experimental data obtained from a plant fed with MSW landfill leachate-polluted groundwater. The plant consisted of two parallel lines composed of a coagulation-flocculation stage at high pH followed by a stripping tower. Six combinations of water pH and temperature conditions were tested. Maximum precipitation was 1,400 kgCaCO 3 after a period of 120days, observed at inlet pH and temperatures of 10.5 and 38 °C The maximum removal efficiency of ammonia was reported as 91%, 87% and 80% respectively. Finally, a good relationship between the loss of efficiency in ammonia removal and the increase of precipitating CaCO 3 to the tower plain area ratio, valid for all water pH and temperatures, has been found., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

A conventional biotrickling filter for airborne ammonia nitrification has been modified, by converting the liquid sump into a biological denitrifying reactor. The biotrickling filter achieves an average ammonia removal efficiency of 92.4 %, with an empty bed retention time (EBRT) equal to 36 s and an average ammonia concentration of 54.7 mg Nm -3 in the raw air stream. The denitrification reactor converts ammonia into inert gas N 2 , in addition to other important advantages connected to the alkaline character of the biochemical pathway of the denitrifying bacteria. Firstly, the trickling water crossing the denitrification reactor underwent a notable pH increase from 7.3 to 8.0 which prevented the acidic inhibition of the nitrifying bacteria due to the buildup of nitric and nitrous acids. Secondly, the pH increase created the ideal conditions for the autotrophic nitrifying bacteria. The tests proved that an ammonia removal efficiency of above 90 % can be achieved with an EBRT greater than 30 s and a volumetric load lower than 200 g NH 3  m -3  day -1 . The results of the biofilm observation by using a scanning confocal laser microscope are reported together with the identification of degrading bacteria genera in the biotrickling filter. The efficiency of the plant and its excellent operational stability highlight the effectiveness of the synergistic action between the denitrification reactor and the biotrickling filter in removing airborne ammonia.

Background: The diffusion of cross-sectional imaging has recently permitted the detection of an increasing number of incidentalomas localized in the distal pancreas. Currently, there are no studies in the literature exploring the laparoscopic approach as treatment for left-sided pancreatic incidentalomas., Methods and Results: We report a series of 20 incidentalomas localized in the body and tail of the pancreas treated with laparoscopic surgery over the period 2010-2014. The incidental masses of our series included a great variety of histotypes and a relevant proportion of malignant lesions. In two cases, the laparoscopic procedures were converted to open surgery. No postoperative death was observed. The postoperative pancreatic fistula rate was 20 %, and the new-onset diabetes rate was 25 %., Conclusions: Left-sided pancreatic incidentalomas in patients with minor comorbidities can be safely treated with laparoscopic approach. Only clinical trials will confirm whether laparoscopic surgery is an effective treatment for malignant lesions.

In this study, the long-term tailing derived from the storage process of contaminants in low-permeability zones is investigated. The release from these areas in the groundwater can be considered a long-term source that often undermines remediation efforts. An Image Analysis technique is used to analyze the process and evaluate the concentrations of a tracer at different points of the test section. Furthermore, the diffusive flux from the low-permeability lenses is determined. To validate the proposed technique, the results are compared with samples, and the diffusive fluxes resulting from the low-permeability zones of the reconstructed aquifer are compared with a theoretical approach.

Previous studies suggest that genetic variants in CHRNA7, which encodes for the major subunit of the acetylcholine receptor (α7-nAChR), are associated with the clinical response to cholinesterase inhibitors (ChEI) in Alzheimer's disease (AD) patients. We sought to replicate the association of two SNPs in the CHRNA7 gene, rs6494223 and rs8024987, with response to ChEI treatment in an Italian cohort of 169 AD patients, further extending the study to gene-level analysis. None of the tested variants was associated with clinical response. However, rs6494223 showed a consistent effect direction (OR = 1.4; p = 0.17), which after meta-analysis with previous study yielded a significant result (OR = 1.57, p = 0.02, I2 = 0%).

The dismemberment of a corpse is fairly rare in forensic medicine. It is usually performed with different types of sharp tools and used as a method of concealing the body and thus erasing proof of murder. In this context, the disarticulation of body parts is an even rarer event. The authors present the analysis of six dismemberment cases (well-preserved corpses or skeletonized remains with clear signs of dismemberment), arising from different contexts and in which different types of sharp tools were used. Two cases in particular showed peculiar features where separation of the forearms and limbs from the rest of the body was performed not by cutting through bones but through a meticulous disarticulation. The importance of a thorough anthropological investigation is thus highlighted, since it provides crucial information on the manner of dismemberment/disarticulation, the types of tools used and the general context in which the crime was perpetrated., (Copyright © 2015 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.)

We evaluated 374 consecutive patients from May 2013 to April 2014 who underwent major cardiac surgery. Each patient had an interview and a neurological clinical examination during the rehabilitation period. Patients with possible peripheral nervous system (PNS) complications underwent further electrodiagnostic tests. Among 374 patients undergoing major heart surgery (coronary artery bypass grafting, valvular heart surgery, ascending aortic aneurysm repair) 23 (6.1 %) developed 34 new PNS complications. We found four brachial plexopathies; four carpal tunnel syndromes; five critical illness neuropathies; three worsening of pre-existing neuropathies; two involvement of X, one of IX and one of XII cranial nerves; three peroneal (at knee), one saphenous, two median (at Struthers ligament), six ulnar (at elbow) mononeuropathies; two meralgia parestheticas. Diabetes is a strong risk factor for PNS complications (p = 0.002); we could not find any other relationship of PNS complications with clinical conditions, demographic data (gender, age) or type of surgical intervention. The mononeuropathies of right arms can be related to ipsilateral vein cannulation; position of body and stretching from chest wall retraction may be the cause of mononeuropathies of left arms (more frequent); the use of saphenous vein and position of the limbs may be the cause of mononeuropathies of the legs; surgical and anesthetical procedures can injure cranial nerves; respiratory failure and infection during the first days after surgery can cause critical illness neuropathies. Careful preoperative assessment and intraoperative management may reduce the risk of long-term PNS complications after cardiac surgery.

Chronic heart failure is a progressive, debilitating disease, resulting in a decline in the quality of life of the patient and incurring very high social economic costs. Chronic heart failure is defined as the inability of the heart to meet the demands of oxygen from the peripheral area. It is a multi-aspect complex disease which impacts negatively on all of the body systems. Presently, there are no texts in the modern literature that associate the symptoms of exercise intolerance of the patient with a dysfunction of the fascial system. In the first part of this article, we will discuss the significance of the disease, its causes, and epidemiology. The second part will explain the pathological adaptations of the myofascial system. The last section will outline a possible osteopathic treatment for patients with heart failure in order to encourage research and improve the general curative approach for the patient.

Thanks to the development of antiretroviral agents to control HIV replication, HIV infection has turned from a fatal disease into a treatable chronic infection. The present work collects the opinions of several experts on the efficacy and safety of recently approved second generation of integrase inhibitors and, in particular, on the role of this new class of drugs in antiretroviral therapy. The availability of new therapeutic options represents an opportunity to ameliorate the efficacy of cART in controlling HIV replication also within viral reservoirs. The personalization of the treatment driven mainly by the management of comorbidities, HIV-HCV co-infections and aging, will be easier with antiretroviral drugs without drug-drug interactions and with a better toxicity and tolerability profile. Future assessment of economic impact for the introduction of new innovative drugs in the field of antiretroviral therapy will likely need some degree of adjustment of the evaluation criteria of costs and benefit which are currently based almost exclusively on morbidity and mortality.

Adjuvant trastuzumab (AT) dramatically improved HER2-positive breast cancer prognosis. Relapsed disease after AT has different patterns and information is available from observational studies. In this Review Chemotherapy regimens combined to anti-HER2 blockade are discussed, focusing in particular the role of anthracyclines, taxanes and capecitabine. The use of trastuzumab beyond progression and the role of other anti-HER2 agents like lapatinib, pertuzumab and T-DM1 are explored, as also dual blockade and in trastuzumab resistant Patients. Metastatic "de novo" HER2 Luminal (co-expression of HER2 and hormone receptors) Patients are eligible for anastrozole and trastuzumab but if pretreated with trastuzumab they are also eligible for lapatinib and letrozole. In any case endocrine treatment plays a complementary role to chemotherapy which remains pivotal. The last topic explored is treatment options for patients with brain metastases where both trastuzumab given concurrent with radiotherapy or lapatinib and capecitabine appear as potentially active., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Young patients with breast cancer (BC) are often concerned about treatment-induced infertility and express maternity desire. Conception after BC does not seem to affect outcome, but information in estrogen-receptor positive (ER+) disease is not definitive. From September 2012-March 2013, 212 evaluable patients with ER+ early BC, <37 years at diagnosis, from 5 regions (Europe/US/Canada/Middle-East/Australia) answered a survey about fertility concerns, maternity desire and interest in a study of endocrine therapy (ET) interruption to allow pregnancy. Overall, 37% of respondents were interested in the study; younger patients (≤30 years) reported higher interest (57%). Motivation in younger patients treated >30 months was higher (83%) than in older women (14%), interest was independent of age in patients treated for ≤30 months. A prospective study in this patient population seems relevant and feasible. The International-Breast-Cancer-Study-Group (IBCSG), within the Breast-International-Group (BIG) - North-American-Breast-Cancer-Groups (NABCG) collaboration, is launching a study (POSITIVE) addressing ET interruption to allow pregnancy., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objectives: To develop a comparative, cost-effectiveness, and budget impact analysis of Therakos online extracorporeal photopheresis (ECP) compared with the main alternatives used for the treatment of steroid-refractory/resistant chronic graft-versus-host disease (cGvHD) in Italy., Methods: The current therapeutic pathway was identified by searching medical databases and from the results of a survey of practice in Italian clinical reference centers. A systematic review was performed to evaluate the efficacy and safety of second-line alternatives. Budget impact and cost-effectiveness analyses were performed from the Italian National Health Service perspective over a 7-year time horizon through the adaption of a Markov model. The following health states were considered: complete and partial response, stable disease, and progression. A discount rate of 3% was applied to costs and outcomes., Results: The most common alternatives used in Italy for the management of steroid-refractory/resistant cGvHD were ECP, mycophenolate, pentostatin, and imatinib. The literature review highlighted that complete and partial responses are higher with ECP than with the alternatives while serious adverse events are less common. The economic analysis showed that Therakos online ECP represents the dominating alternative, in that it delivers greater benefit at a lower cost. In fact, according to the alternatives considered, cost saving ranged from €3237.09 to €19,903.51 per patient with 0.04 to 0.21 quality-adjusted life-year gained., Conclusions: Therakos online ECP should be considered an effective, safe, and cost-effective alternative in steroid-refractory/resistant cGvHD. There is inequality in access, and a dedicated reimbursement tariff, however, should be introduced to overcome these barriers., (Copyright © 2015 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

Background: Obesity represents an important public health issue. An assessment of its costs would be useful to provide recommendations for policy and decision-making strategies. The aims of our study were to carry out a systematic review to assess the economic burden of adult obesity in terms of direct and indirect costs and to perform a quality appraisal of the analysed studies., Methods: A literature search was carried out on PubMed, Scopus and Cochrane Library to retrieve cost-of-illness (COI) analyses focused on adult (aged 18 years or more) overweight or obese people and published up to 2013. COI analyses that considered direct and indirect costs were included. Each included manuscript was independently appraised by three groups of researchers on the basis of the British Medical Journal Drummond's checklist., Results: Approximately 2044 articles were initially retrieved, and 17 were included in the current review. The included studies showed a medium-high-quality level. The available studies seemed to be heterogeneous both in terms of methodology and results reporting. However, as many studies have been conducted from the payer perspective, just direct medical costs can be considered exhaustive. As only three studies included considered also indirect costs, there is no strong evidence to give a comprehensive picture of this phenomenon also from the societal perspective., Conclusion: The review confirmed that obesity absorbs a huge amount of health-care resources. Further research is therefore needed to better understand the economic impact and to identify and promote public health strategies to tackle obesity., (© The Author 2014. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.)

Antimetabolites are a class of effective anticancer drugs interfering in essential biochemical processes. 5-Fluorouracil (5-FU) and its prodrug Capecitabine are widely used in the treatment of several solid tumors (gastro-intestinal, gynecological, head and neck, breast carcinomas). Therapy with fluoropyrimidines is associated with a wide range of adverse effects, including diarrhea, dehydration, abdominal pain, nausea, stomatitis, and hand-foot syndrome. Among the 5-FU side effects, increasing attention is given to cardiovascular toxicities induced at different levels and intensities. Since the mechanisms related to 5-FU-induced cardiotoxicity are still unclear, we examined the effects of 5-FU on primary cell cultures of human cardiomyocytes and endothelial cells, which represent two key components of the cardiovascular system. We analyzed at the cellular and molecular level 5-FU effects on cell proliferation, cell cycle, survival and induction of apoptosis, in an experimental cardioncology approach. We observed autophagic features at the ultrastructural and molecular levels, in particular in 5-FU exposed cardiomyocytes. Reactive oxygen species (ROS) elevation characterized the endothelial response. These responses were prevented by a ROS scavenger. We found induction of a senescent phenotype on both cell types treated with 5-FU. In vivo, in a xenograft model of colon cancer, we showed that 5-FU treatment induced ultrastructural changes in the endothelium of various organs. Taken together, our data suggest that 5-FU can affect, both at the cellular and molecular levels, two key cell types of the cardiovascular system, potentially explaining some manifestations of 5-FU-induced cardiovascular toxicity.

Background: Deintensification and less drug regimen (LDR) antiretroviral therapy (ART) strategies have proved to be effective in terms of maintaining viral suppression in human immunodeficiency virus (HIV)-positive patients, increasing tolerability, and reducing toxicity of antiretroviral drugs administered to patients. However, the economic impact of these strategies have not been widely investigated. The aim of the study is to evaluate the economic impact that ART LDR could have on the Italian National Health Service (INHS) budget., Methods: A budget impact model was structured to assess the potential savings for the INHS by the use of ART LDR for HIV-positive patients with a 3 year perspective. Data concerning ART cost, patient distribution within different ARTs, and probabilities for patients to change ART on a yearly basis were collected within four Italian infectious diseases departments, providing ART to 13.7% of the total number of patients receiving ART in Italy., Results: The LDR investigated (protease inhibitor-based dual and monotherapies) led to savings for the hospitals involved when compared to the "do nothing" scenario on a 3 year basis, between 6.7% (23.11 million €) and 12.8% (44.32 million €) of the total ART expenditures. The mean yearly cost per patient is reduced from 9,875 € in the do nothing scenario to a range between 9,218 € and 8,615 €. The use of these strategies within the four departments involved would have led to a reduction of ART expenditures for the INHS of between 1.1% and 2.1% in 3 years., Conclusion: ART LDR simplification would have a significant impact in the reduction of ART-related costs within the hospitals involved in the study. These strategies could therefore be addressed as a sustainable answer to the public financing reduction observed within the INHS in the last year, allowing therapies to be dispensed without affecting the quality of the services provided.

Background Context: In spinal surgery, newly developed technology seems to play a key role, especially with the use of computer-assisted image-guided navigation, giving excellent results. However, these tools are expensive and may not be affordable for many facilities., Purpose: To compare the cost-effectiveness of preoperative versus intraoperative CT (computed tomography) guidance in spinal surgery., Study Design: A retrospective economic study., Methods: A cost-effectiveness study was performed analyzing the overall costs of a population of patients operated on for lumbar degenerative spondylolisthesis using an image-guided system (IGS) based on a CT scan. The population was divided into two groups according to the type of CT data set acquisition adopted: Group I (IGS based on a preoperative spiral CT scan), Group II (IGS based on an intraoperative CT scan-O-Arm system). The costs associated with each procedure were assessed through a process analysis, where clinical procedures were broken down into single phases and the related costs from each phase were evaluated. No benefits in any form have been or will be received from commercial parties directly or indirectly related to the subject of this article., Results: Four hundred ninety-nine patients met the criteria for this study. In total, 2,542 screws were inserted with IGS. Baseline data were similar for the two groups, as were hospitalization and complications. The surgical time was 119±43 minutes in Group I and 92±31 minutes in Group II. The full cost of the two procedures was analyzed: the mean cost, using the O-Arm system (Group II), was found to be €255.83 (3.80%) less than the cost of Group I. Moreover, the O-Arm system was also used in other surgical procedures as an intraoperative control, thus reducing the final costs of radiologic examinations (a reduction of around 550 CT scans/year)., Conclusions: In conclusion, the authors of the study are of the opinion that the surgical procedure of pedicle screw fixation, using a CT-based computer-guidance system with support of the O-Arm system, allows a shortening of procedure time that might improve the clinical result. However, the present study failed to determine a clear cost-effectiveness with respect to other CT-based IGS., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Despite the success of multiple-drug therapy regimens, the idea of treating human immunodeficiency virus (HIV) infection with fewer drugs is captivating due to issues of convenience, long-term toxicities and costs. This study investigated the impact on a local health budget of the introduction of a protease inhibitor (PI)-based antiretroviral monotherapy. An analysis of 23,721 administrative records of HIV-infected patients and a health technology assessment (HTA) were performed to assess cost-effectiveness, budget, organizational, ethics, and equity impact. Data showed that monotherapy had a annual cost of € 7,076 (patient with undetectable viral load) and € 7,860 (patient with detectable viral load), and that its implementation would realise economic savings of between 12 and 24 million euro (between 4.80% and 9.72% of the 2010 total regional budget expenditure for HIV management) in the first year, with cumulated savings of between 48 and 145 million euro over the following five years. Organizational, ethical and equity impact did not indicate any significant differences. The study suggests that for specific categories of patients monotherapy may be an alternative to existing therapies. Its implementation would not result in higher operating costs, and would lead to a reduction in total expenditure.

We report the case of a 77-year-old male patient who was admitted to our institution for non-ST segment elevation myocardial infarction. Coronary angiography showed a sub-occlusive lesion of the distal left anterior descending artery (LAD) in the context of a diffuse atherosclerotic disease involving a very long segment of the vessel (about 80mm in length by visual estimation). Pre-dilatation was performed in the mid calcified segment of the LAD with a non-compliant balloon inducing vessel dissection. An everolimus-eluting bioresorbable vascular scaffold (EEBVS) was then advanced in the LAD but the first delivery attempt at the distal site failed because of friction between the EEBVS struts and the calcified vessel wall. In order to facilitate EEBVS delivery, a 5Fr catheter system (Heart Rail II, Terumo, Tokyo, Japan) was advanced in the mid LAD within a standard 6Fr guiding catheter facilitating a non-traumatic deep intubation up to the mid LAD. This strategy increased back-up support facilitating the delivery, beyond the site of resistance, of four EEBVS implanted in overlap. This case demonstrated the successful use of a guide catheter extension system to deliver multiple EEBVS in a patient with a long, calcified LAD lesion., (© 2014.)

The presence of a severe calcified peripheral artery lesion is responsible for a poor response to balloon dilation, due to significant acute vessel recoil and frequent flow-limiting dissections requiring stent implantation. This possibility could be associated with very high compression and/or fracture rates particularly in cases of lesion located at the mobile joints. In this setting directional atherectomy offers the theoretical advantages of eliminating stretch injury on arterial walls and reducing the restenosis rate by direct plaque excision. In this report, we present a case of critical hand ischemia due to a heavily calcified axillary artery lesion managed by directional atherectomy and balloon angioplasty followed by immediate angiographic success and sustained clinical benefit up to 3 years of follow-up.

Narrow-band imaging is a young optical enhancement technology for endoscopy. It is a filter to the standard white light which increases the contrast between underlying vasculature and epithelial strata of the mucosa, improving the detection of bladder cancer with particular regard to high grade, flat lesions. Narrow band imaging is absolutely safe, may be used any time during a procedure, either during office cystosopy or transurethral resection, and implies a minimal burden for the healthcare provider given the absence of a learning curve and the limited cost of the camera and light source. The ameliorated detection translates into an improved management of the disease and a lower recurrence risk in prospective randomized studies, suggesting the inclusion of the technology in daily clinical practice.

The advent of drug-eluting stents (DES) associated with improvements in interventional techniques, encouraged the use of percutaneous coronary intervention (PCI) for unprotected left main (ULM) stenosis because of the lower need of repeat revascularization compared to the bare-metal stents (BMS). Nevertheless, ULM DES in-stent restenosis (ISR) continues to occur. The choice of treatment strategy (medical treatment, repeated PCI, or coronary artery bypass graft) for ULM DES-ISR depends primarily on several clinical and angiographic factors, making optimal patient selection crucial in the appropriate treatment of ULM-ISR lesions and achievement of favorable long-term outcomes. We describe in this report a successful modern approach to manage a distal ULM DES-ISR following a 2-stent strategy, consisting in the kissing inflation of two DEBs in both branches of the bifurcation., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objectives: Two human papillomavirus (HPV) vaccines are currently available: a bivalent HPV-16/18 and a quadrivalent HPV-6/11/16/18 vaccine. The vaccines may have different sustained- and cross-protection levels against non-vaccine oncogenic HPV-types. This study investigated the potential difference in clinical and economic impacts provided by two HPV vaccines in Italy., Methods: A prevalence-based model estimated the potential net difference in HPV-related lesions (abnormal pap smear, cervical intraepithelial neoplasia (CIN), cervical cancer (CC) and genital warts (GW)) and associated costs generated by the two vaccines. Incidence and treatment costs were obtained from Italian and European sources. Vaccine efficacy rates were based on published data for each vaccine. Lifetime vaccine efficacy was assumed. Results are reported over one year after reaching a steady state. Sensitivity analyses were performed on the lesion incidence, vaccine effectiveness, treatment costs and sustained protection., Results: The bivalent vaccine would prevent an additional reduction of 7976 abnormal pap smears; 601 CIN1; 1826 CIN2/3 and 295 CC cases compared to the quadrivalent vaccine while 25,848 genital wart cases would be prevented by the quadrivalent vaccine. The additional cost averted with the bivalent vaccine was estimated at €2,385,354 per year compared to the quadrivalent vaccine. The most influential parameters were CC- and GW-related costs and the difference in sustained protection., Conclusions: Our model suggests that, in the Italian setting, the bivalent vaccine would prevent more precancerous and CC lesions than the quadrivalent vaccine. This translates into a greater cost averted for the bivalent vaccine, which could completely offset savings in GW-related costs associated with the quadrivalent vaccine., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Invasive and metastatic cells must cross basement membranes (BMs) in order to disseminate to distant sites. The 'chemoinvasion assay' using a reconstituted basement membrane, matrigel, in Boyden blind-well chambers was developed 25 years ago as a tool for invasion and metastasis research. Since then, it was adapted for investigation of how different cells types engage with and penetrate basement membrane, including research in angiogenesis, invasive cell migration, protease functions, and preclinical development of anti-invasive and anti-angiogenic agents. As novel mechanisms of metastasis and angiogenesis come to light and old paradigms are challenged, we examine how the assay can still provide innovative insights. We review established applications and variants of the matrigel invasion assay, highlight key findings derived from it and discuss future developments, including roles for accessory and cancer stem cells., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Capecitabine is an orally available fluoropyrimidine carbamate that selectively delivers fluorouracil (5-FU) to tissues expressing high levels of thymidine phosphorylase (TP) such as tumors. The drug has demonstrated efficacy in metastatic breast cancer, colorectal, and pancreatic cancer. Although these are considered safe drugs, a growing body of literature reports adverse cardiac effects. Clinical trials indicate that capecitabine has a cardiac toxicity similar to that of infused fluoropyrimidines such as 5-FU. Here, we review cardiotoxicity in the use of fluoropyrimidines, with particular attention toward capecitabine. We also describe a severe, reversible cardiac event that occurred in a 39-year-old woman, with no cardiac risk factors, treated with capecitabine for advanced breast cancer. This review and our experience confirm that fluoropyrimidine cardiotoxicity is an infrequent but documented side effect. Oncology patients under treatment should be closely observed and monitored for cardiac symptoms with particular attention in case of signs or symptoms of cardiovascular complications. The implementation of cardio-oncology interdisciplinary teams should, in the future, reduce the impact of cancer treatment-associated cardiotoxicity syndromes., (© 2010 Wiley Periodicals, Inc.)

Aims: Implantable cardioverter defibrillators (ICD) improve survival in selected patients with left ventricular dysfunction or heart failure (HF). The objective is to estimate the number of ICD candidates and to assess the potential impact on public health expenditure in Italy and the USA., Methods and Results: Data from 3513 consecutive patients (ALPHA study registry) were screened. A model based on international guidelines inclusion criteria and epidemiological data was used to estimate the number of eligible patients. A comparison with current ICD implant rate was done to estimate the necessary incremental rate to treat eligible patients within 5 years. Up to 54% of HF patients are estimated to be eligible for ICD implantation. An implantation policy based on guidelines would significantly increase the ICD number to 2671 implants per million inhabitants in Italy and to 4261 in the USA. An annual increment of prophylactic ICD implants of 20% in the USA and 68% in Italy would be necessary to treat all indicated patients in a 5-year timeframe., Conclusion: Implantable cardioverter defibrillator implantation policy based on current evidence may have significant impact on public health expenditure. Effective risk stratification may be useful in order to maximize benefit of ICD therapy and its cost-effectiveness in primary prevention.

Angiogenesis is a highly regulated physiological process that has been studied in considerable detail given its importance in several chronic pathologies. Many endogenous factors and hormones intervene in the regulation of angiogensis and classical as well as targeted drugs have been developed for its control. Angiogenesis inhibition has come off the bench and entered into clinical application for cancer therapy, particularly for metastatic disease. While the clinical benefit is currently in terms of months, preclinical data suggest that novel drugs and drug combinations could lead to substantial improvement. The many targets of endogenous angiogenesis inhibitors reflect the complexity of the process; in contrast, current clinical therapies mainly target the vascular endothelial growth factor system. Cancer chemopreventive compounds can retard tumor insurgence and delay or prevent metastasis and many of these molecules hinder angiogenesis, a mechanism that we termed angioprevention. Angiopreventive drugs appear to prevalently act through the inhibition of the pro-inflammatory and anti-apoptotic player NFkappaB, thus contrasting inflammation dependent angiogenesis. Relatively little is known concerning the effects of these angiogenesis inhibitors on gene expression of endothelial cells, the main target of many of these molecules. Here we provide an exhaustive list of anti-angiogenic molecules, and summarize their effects, where known, on the transcriptome and functional genomics of endothelial cells. The regulation of specific genes can be crucial to preventive or therapeutic intervention. Further, novel targets might help to circumvent resistance to anti-angiogenic therapy. The studies we review are relevant not only to cancer but also to other chronic degenerative diseases involving endothelial cells, such as cardiovascular disorders, diabetes, rheumatoid arthritis and retinopaties, as well as vessel aging.

Scope: Patients with tracheostomy tube after major cardiac surgery undergoing Cardiac Rehabilitation Program often present swallowing disorders that need a specific evaluation. This study aimed at validating the usefulness of a swallowing screen protocol in order to obtain an early assessment of dysphagia and to prevent aspiration, malnutrition and dehydration risks., Materials and Methods: The protocol has been applied to 38 consecutive patients with tracheostomy tube after cardiac surgery between September 2007 and December 2009. The average age of patients was 73 +/- 6 years; the average value of left ventricular ejection fraction was 41 +/- 4%. The protocol included a water swallowing test and a specific swallowing test with blue dye. During tests, the presence of signs of swallowing dysfunction was evaluated and oxygen saturation levels were monitored., Results: Out of 38 patients, 2 did not show any swallowing deficits; 18 showed deficits in the water swallowing test even though they presented a preserved swallowing function during specific swallowing test. All these 20 patients (53%), before discharge, restarted an oral feeding and obtained an adequate body mass index and effective coughing, so they were soon decannulated. Twelve patients (31%) showed deficits during the water swallowing test, confirmed by the specific swallowing test with blue dye: the tracheostomy tube was not removed and a specific program of swallowing rehabilitation was performed. Before discharge all patients restarted an oral feeding, recovered an effective coughing and were decannulated. Six patients (16%), because of persistent dysphagia, underwent percutaneous endoscopic gastrostomy. None of these 38 patients developed ab ingestis pneumonia, dehydration or malnutrition., Conclusions: An early assessment of swallowing in patients with tracheostomy tube after cardiac surgery allows the selection of patients with higher aspiration risk, preventing possible severe complications.

Following preventive chemotherapy covering the entire population in the two endemic regions in Cambodia, the prevalence of schistosomiasis dropped from 77% in 1995 to 0.5% in 2003. The study presented here reports on the running cost of the control programme, and evaluates its cost-effectiveness and cost-benefit. Financial costs were assessed using data taken from the annual reports of the National Center for Malaria Control, the Cambodian institution responsible for the control activities. Other data were collected from interviews with provincial and district staff. The analysis was conducted from the point of views of the Cambodian Ministry of Health and that of the society, and the comparison was undertaken using the "do-nothing" option. The cost to treat an individual for the 9 years period of the implementation phase was 9.22 USD (1.02 per year), the cost for each severe infection avoided was 61.50 USD and 6531 USD for each death avoided. The drug cost corresponds on average to 17.34% of the programme's implementation cost. The cost of bringing one severely infected individual of productive age to complete productivity, was estimated at 114 USD and for 1 USD invested in the programme the return in increased productivity, for the economic system, was estimated to be 3.85 USD. The control programme demonstrated significant economical advantages. However, its costs are too high to be entirely supported by the Cambodian Ministry of Health., (Copyright 2009 Elsevier B.V. All rights reserved.)

Due to the aging of the populations of developed countries and a common occurrence of risk factors, it is increasingly probable that a patient may have both cancer and cardiovascular disease. In addition, cytotoxic agents and targeted therapies used to treat cancer, including classic chemotherapeutic agents, monoclonal antibodies that target tyrosine kinase receptors, small molecule tyrosine kinase inhibitors, and even antiangiogenic drugs and chemoprevention agents such as cyclooxygenase-2 inhibitors, all affect the cardiovascular system. One of the reasons is that many agents reach targets in the microenvironment and do not affect only the tumor. Combination therapy often amplifies cardiotoxicity, and radiotherapy can also cause heart problems, particularly when combined with chemotherapy. In the past, cardiotoxic risk was less evident, but it is increasingly an issue, particularly with combination therapy and adjuvant therapy. Today's oncologists must be fully aware of cardiovascular risks to avoid or prevent adverse cardiovascular effects, and cardiologists must now be ready to assist oncologists by performing evaluations relevant to the choice of therapy. There is a need for cooperation between these two areas and for the development of a novel discipline, which could be termed cardio-oncology or onco-cardiology. Here, we summarize the potential cardiovascular toxicities for a range of cancer chemotherapeutic and chemopreventive agents and emphasize the importance of evaluating cardiovascular risk when patients enter into trials and the need to develop guidelines that include collateral effects on the cardiovascular system. We also discuss mechanistic pathways and describe several potential protective agents that could be administered to patients with occult or overt risk for cardiovascular complications.

Objectives: Recently, a new echocardiographic nonflow corrected index (ejection fraction/velocity ratio [EFVR] = percent left ventricular ejection fraction [EF]/maximum aortic gradient) has been introduced and has shown excellent accuracy in quantifying the effective orifice area (EOA) in native aortic valves and bio-prostheses. The objective of this study was to assess the utility of the EFVR to quantify the indexed EOA in patients with an aortic bioprosthesis and left ventricular dysfunction considering an indexed EOA value of 0.85 cm(2)/m(2) or less to be indicative of a prosthesis-patient mismatch (PPM), defined as an EOA of the inserted prosthetic valve of less than that of the normal human valve., Methods: We studied 100 patients (62 men and 38 women; mean age +/- SD, 71 +/- 8.6 years) with an aortic bioprosthesis and left ventricular dysfunction (EF < or =49%), and we evaluated the indexed EOA by both the continuity equation (CE) and EFVR., Results: We found a significant linear correlation between the CE and EFVR (r = 0.85; P < .0001) and good agreement between the two methods in identifying patients with an indexed EOA of 0.85 cm(2)/m(2) or less; the correlation began to become nonlinear for patients with an indexed EOA of greater than 1.2 cm(2)/m(2), which was not clinically relevant. Notably, all 11 patients with a discrepancy between the indexed EOA and EFVR (ie, EFVR < or =1.0 and indexed EOA >0.85 cm(2)/m(2)) also showed an indexed EOA of greater than 0.85 but less than or equal to 1.0 cm(2)/m(2) (meaning the presence of a mild PPM)., Conclusions: The EFVR can be considered a reliable echocardiographic alternative to the CE, especially in conditions in which that is technically difficult, allowing identification of a PPM (indexed EOA < or =0.85 cm(2)/m(2)) with excellent sensitivity and specificity.

Carbohydrates (CHO) can be classified on the basis of their glycemic index (GI), and the use of this classification has been increasingly supported by science. Because of its impact on blood glucose and insulin responses following the ingestion of CHO foods, the GI has been studied in many fields of medicine, including sport nutrition. As a new tool in sport nutrition, glycemic index manipulation has been evaluated to improve the first and second phases of glycogen recovery, glycogen load, and exercise metabolism, including control of rebound hypoglycemia and, it is interesting to note, stimulation of lipid oxidation for longer availability of glucose sources during endurance exercise. Although attractive, the use of GI in sport nutrition has received only partial support from available experimental evidence. At the biochemical level, consistent evidence has been attained to suggest that GI manipulation can determine variations in adipocyte lipolysis, plasma free fatty acids levels, and lipid and CHO oxidation rates during exercise. However, when the effects of GI manipulation have been assessed at the functional level, the results have been inconsistent, with evidence of improved exercise performance in some studies, but not in many others. The purpose of the current article is to review the effects and limits of GI manipulation in sport nutrition, and to propose an overall strategy for its application.

Mountain biking is a popular outdoor recreational activity and an Olympic sport. Cross-country circuit races have a winning time of approximately equal 120 minutes and are performed at an average heart rate close to 90% of the maximum, corresponding to 84% of maximum oxygen uptake (VO2max). More than 80% of race time is spent above the lactate threshold. This very high exercise intensity is related to the fast starting phase of the race; the several climbs, forcing off-road cyclists to expend most of their effort going against gravity; greater rolling resistance; and the isometric contractions of arm and leg muscles necessary for bike handling and stabilisation. Because of the high power output (up to 500W) required during steep climbing and at the start of the race, anaerobic energy metabolism is also likely to be a factor of off-road cycling and deserves further investigation. Mountain bikers' physiological characteristics indicate that aerobic power (VO2max >70 mL/kg/min) and the ability to sustain high work rates for prolonged periods of time are prerequisites for competing at a high level in off-road cycling events. The anthropometric characteristics of mountain bikers are similar to climbers and all-terrain road cyclists. Various parameters of aerobic fitness are correlated to cross-country performance, suggesting that these tests are valid for the physiological assessment of competitive mountain bikers, especially when normalised to body mass. Factors other than aerobic power and capacity might influence off-road cycling performance and require further investigation. These include off-road cycling economy, anaerobic power and capacity, technical ability and pre-exercise nutritional strategies.

The aim of this study was to examine the relationship between push-time and final race time in skeleton participants during a series of major international competitions to determine the importance of the push phase in skeleton performance. Correlations were computed from the first and second heat split data measured during 24 men and 24 women skeleton competitions. Body mass, height, age, and years of experience of the first 30 men and women athletes of the skeleton, bobsleigh and luge 2003-2004 World Cup ranking were used for the comparison between sliding sports. Moderate but significant correlations (p < 0.05) were found between push-time and final race time in men (r(mean) = 0.48) and women (r(mean) = 0.63). No correlations were found between changes in the individual push-time between the first and second heat with the corresponding changes in final race time. The bobsleigh sliders are heavier than the athletes of the other sliding disciplines. Luge athletes have more experience and are younger than bobsleigh and skeleton sliders. The results of this study suggest that a fast push phase is a prerequisite to success in competition and confirms that the selection of skeleton athletes based on the ability to accelerate to a maximum speed quickly could be valid. However, a good or improved push-time does not ensure a placement in the top finishing positions. On the basis of these results, we suggest that strength and power training is necessary to maintain a short push-time but additional physical training aimed to enhance the push phase might not reflect performance improvements. The recruitment of younger athletes and an increase of youthful competitive activity may be another effective way to reach international competitive results.

Background: Sudden cardiac death (SDC) is responsible for approximately 60-70% of deaths in New York Heart Association (NYHA) class II congestive heart failure (CHF) patients. Recently, microvolt-level T wave alternans has been proposed as a new noninvasive tool to identify CHF patients at risk for SCD and ventricular tachycardia/fibrillation (VT/VF)., Objectives: To determine the prognostic value of MTWA in NYHA class II patients., Methods: Among 181 consecutive CHF patients with ischemic and nonischemic cardiomyopathy, 73 patients in NYHA class II with left ventricular ejection fraction <45% were selected and prospectively investigated. MTWA was determined during bicycle exercise testing. The study end point was defined as SCD, documented sustained VT/VF and appropriate implantable cardioverter defibrillator (ICD) shock., Results: MTWA was positive in 30 (41%) patients, negative in 26(36%) patients and indeterminate in 17 (23%) patients. During an average follow-up of 17.1+/-7.4 months, seven patients had an arrhythmic event in the MTWA positive group, whereas one and no events occurred in the indeterminate and negative group, respectively. From Kaplan-Meier univariate analysis and multivariate Cox analysis, MTWA was a significant arrhythmic risk stratifier (p=0.01 and p=0.03, respectively). Sensitivity, specificity, negative and positive predictive values of MTWA were 100%, 53%, 100% and 24%, respectively., Conclusion: Our data suggest that MTWA is a promising predictor of arrhythmic events in NYHA class II CHF patients.

The authors present a critical appraisal of the biological bases of altered fractionation and a brief overview of published randomized trials with conventional fractionation as the control arm, reviews and meta-analysis on altered fractionation radiotherapy in head and neck cancer. The major controversial issues emerging from these studies are reviewed and the limiting factors which so far have prevented the widespread use of altered fractionation regimens in current clinical practice are analyzed. Future perspectives regarding predictive biological assays for patient selection and the integration of altered fractionation regimens with radiochemotherapy protocols, biomodulators and novel radiotherapy techniques are also reviewed and summarized.

Aims: Pulmonary vein (PV) isolation is a curative treatment for patients with atrial fibrillation. The aim of this study was to evaluate prospectively the effects of adenosine administration on the PV activity and atrio-venous conduction after PV isolation., Methods and Results: Twenty-nine patients (21 m; age: 55+/-8 years) were submitted to ostial PV isolation guided by basket catheter recordings. After successful isolation, the effects of a 12 mg intravenous bolus of adenosine were tested in 62 PVs. In 22/62 PVs (35%), left atrium (LA)-to-PV conduction was transiently (16.6+/-7.1 s, range: 3.8-27.9 s) or permanently (3 PVs) restored in response to adenosine administration. The prevalence of this phenomenon was 39% in left superior PVs, 43% in right superior PVs, and 22% in left inferior PVs (p=0.365). It occurred more frequently in the presence of dissociated PV activity (11/15 PVs, 73% vs. 11/47 PVs, 23%; p=0.002), whereas it was not influenced by the median duration of the radiofrequency current (RFC) delivery for each PV [19 (IQR: 12-26) min vs. 16 (IQR: 11-24) min: p=0.636]. A lengthening or shortening of the LA-PV conduction time was observed at LA-PV conduction appearance and disappearance in 36% and 55% of the cases, respectively. Further RFC applications (median: 5.5 min, IQR: 4-11 min) at the residual conduction breakthrough(s) indicated by the basket catheter recordings definitively eliminated adenosine-induced recovery of LA-PV conduction in all cases. Finally, when present, intrinsic PV discharge was invariably depressed by adenosine administration., Conclusions: Adenosine may transiently or permanently re-establish LA-PV conduction after apparently successful PV isolation. This phenomenon is abolished by additional RFC delivery. However, its possible influence on the clinical results of PV ablation must be evaluated by properly designed, randomized studies.

Since 1992 we have performed laparoscopic cholecystectomy with 3 trocars (10, 10 and 5 mm) while most surgeons use 4. In our 10 years of experience a total of 1,243 cholecystectomies have been performed with the 3-trocar technique. The overall conversion rate is 0.75%. In 5.7% of cases we used a fourth trocar in order to avoid anatomical difficulties or to perform intraoperative cholangiography. All interventions are technically feasible, even in sclerotic cholecystitis and in emergency operations. We describe this technique which can be considered an economic and cosmetically satisfying alternative, that is safe and effective for the patient and easy to perform for the surgeon.

Radiofrequency is the most commonly used energy source for the treatment of cardiac arrhythmias. Despite its high success rate, radiofrequency energy may sometimes present limitations, especially in case of anteroseptal atrioventricular accessory pathways. In these patients, inadvertent atrioventricular block may occur during or after the procedure and a high recurrence rate of conduction over the accessory pathway is observed. Since the late 1970s, cryosurgery has been an integral part of the management of cardiac arrhythmias, and recently, animal and clinical studies demonstrated the feasibility and safety of applying percutaneous catheter cryoablation technology. These studies also showed that reversible cryomapping of high-risk arrhythmogenic sites can be performed before creating permanent lesions. In this preliminary report, we describe the successful use of percutaneous cryoablation for the permanent interruption of conduction over anteroseptal accessory pathways.

We describe a case of post-incisional atrial tachycardia resembling typical atrial flutter on the surface ECG. Typical atrial flutter reentry was ruled out by the results of activation and entrainment mapping. Nevertheless, overdrive pacing from the lateral edge of the cavo-tricuspid isthmus produced tachycardia entrainment with concealed fusion associated with post-pacing and stimulus-to-P wave onset intervals exactly matching the tachycardia cycle length duration and the electrogram-to-P wave onset interval, respectively. Therefore, that site was firstly severed by sequential radiofrequency pulses. However, a transformation of the tachycardia P wave morphology and endocardial activation sequence, not associated with tachycardia termination or cycle length modification occurred. After additional mapping manoeuvres, a relatively small reentrant circuit was identified in the low and mid aspect of the lateral right atrium with the critical isthmus located between the lower border of a cannulation atriotomy and the crista terminalis, close to the inferior vena cava orifice. A single radiofrequency pulse at that site terminated the tachycardia. Both the electrocardiographic pattern and the endocardial mapping data obtained in our case might be explained by a split of the reentrant wavefront into a secondary wavelet which freely propagated through the cavo-tricuspid isthmus without completing the peritricuspid loop. In conclusion, bystander cavo-tricuspid isthmus activation during atrial tachycardia may simulate a typical atrial flutter pattern on the surface ECG. Further studies should evaluate the prevalence of this propagation pattern in post-incisional atrial reentry and atypical atrial flutters, and identify its implications for ablation strategy.