A novel co-monomer based on Ellagic Acid for free radical polymerization of N-vinyl-2-pyrrolidone

INTRODUCTION Ellagic Acid (EA) is one of the most abundant and relevant antioxidants present in fruits such as berries and in pomegranate [1]; on the other hand, its poor solubility both in water and in organic solvents limits its reactivity and its use as food supplements. The aim of the present work is to modify the structure of the EA in order to use it as co-monomer for radical polymerization of N-vinyl-2-pyrrolidone (NVP) achieving two main goals: protection of antioxidant moiety; different release pathway. MATERIALS AND METHODS EA was reacted with methacryloyl chloride via a hetero-phase reaction in anhydrous CH2Cl2 to obtain a high purity tetra-ester allyl derivate (EAMAC). Polymers were then obtained via bulk photopolymerization of N-vinyl-2-pyrrolidon with different quantities of EAMAC in a square-shaped PTFE mold for 1h. The release assay was performed using hydrolytic and enzymatic conditions. RESULTS AND DISCUSSION EAMAC is the only product obtained since other partially substituted esters (i.e. mono-, bi- and three-esters) are not present: it was obtained with high yield ( 4880%w/w) and was fully characterized via 1H-NMR and MS [ESI-Q-Tof MS= 587.48 m/z (EAMAC + Na+)]. Thermal properties were assessed via DSC obtaining a single melting peak at 263\ub0C: degradation starts immediately after melting. EAMAC was used as a co-monomer for NVP bulk photopolymerization; the reaction was performed avoiding the use of photoinitiator. It was observed that the irradiation with UV of EAMAC starts the reaction of polymerization transferring the radical to the NVP. Cross-linked polymers containing different amount of EAMAC were obtained. The release of EA was assessed both using solutions having different pHs and via enzymatic hydrolytic conditions. CONCLUSIONS The reaction of EA with methacryloyl chloride leads to obtain a single, reactive derivate of EA able to react with vinyl monomers, that is highly soluble in organic solvents. Moreover, EAMAC acts as radical initiator avoiding the use of photoinitiator and it leads to obtain crosslinked water-compatible polymers. EA can be released from the polymer and the kinetic of the release is related to the kinetic of the hydrolysis of the ester bonds existing between EA and methacrylic moieties bonded to polyvinyl pirrolydone (PVP) chains. REFERENCES [1] Verotta, L.; Panzella, L.; Antenucci, S.; Calvenzani, V.; Tomay, F.; Petroni, K.; Caneva, E.; Napolitano, A. Fermented pomegranate wastes as sustainable source of ellagic acid: antioxidant properties, anti-inflammatory action, and controlled release under simulated digestion conditions. Submitted to Food Chemistry, 2017 ACKNOWLEDGEMENT Work supported by Fondazione Cariplo and Regione Lombardia for the project \u2018\u2018BIOPLANT\u2019\u2019

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Improved risk stratification of patients with atrial fibrillation: an integrated GARFIELD-AF tool for the prediction of mortality, stroke and bleed in patients with and without anticoagulation.

OBJECTIVES: To provide an accurate, web-based tool for stratifying patients with atrial fibrillation to facilitate decisions on the potential benefits/risks of anticoagulation, based on mortality, stroke and bleeding risks. DESIGN: The new tool was developed, using stepwise regression, for all and then applied to lower risk patients. C-statistics were compared with CHA2DS2-VASc using 30-fold cross-validation to control for overfitting. External validation was undertaken in an independent dataset, Outcome Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF). PARTICIPANTS: Data from 39 898 patients enrolled in the prospective GARFIELD-AF registry provided the basis for deriving and validating an integrated risk tool to predict stroke risk, mortality and bleeding risk. RESULTS: The discriminatory value of the GARFIELD-AF risk model was superior to CHA2DS2-VASc for patients with or without anticoagulation. C-statistics (95% CI) for all-cause mortality, ischaemic stroke/systemic embolism and haemorrhagic stroke/major bleeding (treated patients) were: 0.77 (0.76 to 0.78), 0.69 (0.67 to 0.71) and 0.66 (0.62 to 0.69), respectively, for the GARFIELD-AF risk models, and 0.66 (0.64-0.67), 0.64 (0.61-0.66) and 0.64 (0.61-0.68), respectively, for CHA2DS2-VASc (or HAS-BLED for bleeding). In very low to low risk patients (CHA2DS2-VASc 0 or 1 (men) and 1 or 2 (women)), the CHA2DS2-VASc and HAS-BLED (for bleeding) scores offered weak discriminatory value for mortality, stroke/systemic embolism and major bleeding. C-statistics for the GARFIELD-AF risk tool were 0.69 (0.64 to 0.75), 0.65 (0.56 to 0.73) and 0.60 (0.47 to 0.73) for each end point, respectively, versus 0.50 (0.45 to 0.55), 0.59 (0.50 to 0.67) and 0.55 (0.53 to 0.56) for CHA2DS2-VASc (or HAS-BLED for bleeding). Upon validation in the ORBIT-AF population, C-statistics showed that the GARFIELD-AF risk tool was effective for predicting 1-year all-cause mortality using the full and simplified model for all-cause mortality: C-statistics 0.75 (0.73 to 0.77) and 0.75 (0.73 to 0.77), respectively, and for predicting for any stroke or systemic embolism over 1 year, C-statistics 0.68 (0.62 to 0.74). CONCLUSIONS: Performance of the GARFIELD-AF risk tool was superior to CHA2DS2-VASc in predicting stroke and mortality and superior to HAS-BLED for bleeding, overall and in lower risk patients. The GARFIELD-AF tool has the potential for incorporation in routine electronic systems, and for the first time, permits simultaneous evaluation of ischaemic stroke, mortality and bleeding risks. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier for GARFIELD-AF (NCT01090362) and for ORBIT-AF (NCT01165710)

Two-year outcomes of patients with newly diagnosed atrial fibrillation: results from GARFIELD-AF.

AIMS: The relationship between outcomes and time after diagnosis for patients with non-valvular atrial fibrillation (NVAF) is poorly defined, especially beyond the first year. METHODS AND RESULTS: GARFIELD-AF is an ongoing, global observational study of adults with newly diagnosed NVAF. Two-year outcomes of 17 162 patients prospectively enrolled in GARFIELD-AF were analysed in light of baseline characteristics, risk profiles for stroke/systemic embolism (SE), and antithrombotic therapy. The mean (standard deviation) age was 69.8 (11.4) years, 43.8% were women, and the mean CHA2DS2-VASc score was 3.3 (1.6); 60.8% of patients were prescribed anticoagulant therapy with/without antiplatelet (AP) therapy, 27.4% AP monotherapy, and 11.8% no antithrombotic therapy. At 2-year follow-up, all-cause mortality, stroke/SE, and major bleeding had occurred at a rate (95% confidence interval) of 3.83 (3.62; 4.05), 1.25 (1.13; 1.38), and 0.70 (0.62; 0.81) per 100 person-years, respectively. Rates for all three major events were highest during the first 4 months. Congestive heart failure, acute coronary syndromes, sudden/unwitnessed death, malignancy, respiratory failure, and infection/sepsis accounted for 65% of all known causes of death and strokes for <10%. Anticoagulant treatment was associated with a 35% lower risk of death. CONCLUSION: The most frequent of the three major outcome measures was death, whose most common causes are not known to be significantly influenced by anticoagulation. This suggests that a more comprehensive approach to the management of NVAF may be needed to improve outcome. This could include, in addition to anticoagulation, interventions targeting modifiable, cause-specific risk factors for death. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

The case of 4-vinyl-1,3-dioxolane-2-one: determination of its pseudo-living behavior and preparation of allyl carbonate-styrene co-polymers

This article describes for the first time the pseudo-living radical activity of 4-vinyl-1,3-dioxolane-2-one (VEC) monomer towards a free radical homo-polymerization: a kinetic study of VEC homo-polymerization was performed up to 168 hours and it was found that molecular weights, determined via gel permeation chromatography (GPC), and VEC conversion, measured via H-1 NMR spectroscopy, continue to grow over time showing a molecular weights distribution typical of pseudo-living polymerizations. Until today, in co-polymerization with styrene, just a few VEC moieties could be inserted into VEC-styrene co-polymers; in this work VEC controlled radical activity allows, for the first time, the synthesis of di-block co-polymers between styrene and vinyl groups bearing cyclic carbonate functionalities that can be used for further cross-linking reactions. VEC-styrene copolymers were synthesized with different molar ratios between co-monomers and characterized by GPC analyses and H-1 NMR spectra; excellent reaction yields and solubility in apolar solvents were obtained

Protective features, durability and biodegration study of acrylic and methacrylic fluorinated polymer coatings for marble protection

In the present paper, a new fluorine based methacrylic monomer, 1H,1H,2H,2H-Perfluoro-octyl-methacrylate (POMA), was synthesized via esterification reaction from methacryloyl chloride and 1H,1H,2H,2H-Perfluoro-1- octanol. Furthermore, POMA was used to prepare with methyl methacrylate (MMA) via free radical polymerization a novel fluorinated methacrylic polymer (MMA_POMA), in order to overcome the well-known technical problems related to the use of acrylic monomer-based commercial protectives, such as Paraloid B72\uae. Indeed, in Paraloid B72\uae 12obtainable from the copolymerization reaction of ethyl methacrylate (EMA) and methyl acrylate (MA)- the presence of an acrylic hydrogen atom in alpha to the carbonyl group can start photochemical degradation reactions that are able to promote fungi attack and proliferation. The properties of MMA_POMA and the two references synthesized, EMA_MA and EMA_MA_POMA 12in terms of macromolecular structure, molecular weights, thermal features and water repellency- were determined; furthermore, the long-term behavior of these polymeric protective agents was estimated by means of accelerated aging tests exploiting UV radiations. Their behavior over time was checked via Size Exclusion Chromatography (SEC), Fourier Transform Infrared (FT-IR) spectroscopy and biodegradation assay. Lastly, MMA_POMA resin was applied on two marble substrates 12Calcite and Dolomite- and its wetting properties were successfully assessed and compared to the same features displayed by the reference polymers. This work demonstrates that a polymer protective prepared starting from methacrylic and fluorinated monomers, i.e. MMA and POMA, is an efficient way to obtain resins with satisfactory water repellent properties and enhanced durability than acrylic based polymers without the use of any photo stabilizer additive

Current evidence in designs and fixation surfaces in total hip arthroplasty

Since its introduction in the 1960s, total hip arthroplasty (THA) has proved to be an excellent and reliable mode of treatment for the end stages of hip pathology, with satisfactory clinical outcomes at 15-20 years [1-4]. Following the initial problems which the pioneers accounted in the 1960s and 1970s (such as surgical technique, structural design failures, and infection), in the 1980s, orthopaedic surgeons faced problems of choice of both acetabular and femoral components and the selection of cemented or cementless implant fixation. Soon afterwards, it was proved that the above dilemmas had been misleading since the long-term survival of a THA is a multifactorial issue, since, other than the implant, factors related to the diagnosis, the patient, the surgeon, and surgical technique are also important (Fig. 1.1). However, until now, the implant has been easy to blame for failures. A possible explanation is the fact that we do not have strong evidence supporting implant design and fixation principles. Instead, we have evidence of good and bad recipes, surgeons having learned from devastating clinical failures and patients having often been "fashion victims" [5]. © 2014 Springer-Verlag London. All rights are reserved