Real-World Apremilast Use for Treatment of Plaque Psoriasis in Italy: Patient Perspective, Characteristics, and Clinical Outcomes from the DARWIN Study

IntroductionWhile several european studies have reported real-world apremilast use, patient-perceived benefits, and treatment satisfaction, local reimbursement criteria for apremilast vary and data from Italy are limited.methodsThe cross-sectional DARWIN study enrolled consecutive patients who had initiated apremilast for plaque psoriasis 6 (+/- 1) months prior to enrolment at a single visit across 24 Italian dermatological sites. disease severity was assessed using body surface area (BSA) and physician global assessment (PGA). patient-reported outcomes assessed 6 (+/- 1) months after apremilast initiation were dermatology life quality Index (DLQI), patient benefit Index (PBI), and 9-item treatment satisfaction questionnaire for medication (TSQM-9).ResultsOf 184 patients enrolled between July 2019 and January 2021, 180 were included in the analysis. at apremilast initiation, median (25th-75th percentile) time since psoriasis diagnosis was 8.6 (3.2-22.2) years; median BSA, 10.0% (5.0-16.0); mean (standard seviation, SD) DLQI total score, 13.5 (8.0). over half (54.9%) of patients with available data reported psoriasis had a very or extremely large effect on their quality of life (QoL); half reported itching (50.6%) and/or special areas involvement (50.0%). most (73.9%) had comorbidities and were biologic-naive (81.5%). the most common reasons for initiating apremilast were lack of efficacy of previous treatment (56.7%) and contraindications to other treatments (44.4%). At 6 (+/- 1) months, most patients were continuing apremilast and/or reported a global PBI score >= 1 (minimum clinical benefit) (86.1% and 90.0%, respectively); approximately half achieved BSA <= 3% and/or DLQI total score <= 5 (47.1% and 48.5%); 18.8% achieved PGA = 0; mean (SD) TSQM-9 global treatment satisfaction score was 59.0 (24.8). apremilast was well tolerated; no new safety signals were identified .conclusions patients treated with apremilast for 6 months in Italian clinical practice reported improved QoL, clinically relevant improvements in symptoms, high treatment satisfaction, and high treatment persistence. our data indicate apremilast is a valuable treatment option for moderate plaque psoriasis. study registration clinical trials.gov identifier, NCT04031027

Enhanced ORR activity of S- and N-modified non-noble metal-doped carbons with bamboo-like C nanotubes grafted onto their surface

Discovering low-cost and earth-abundant electrocatalysts for oxygen reduction reaction (ORR) is essential for advanced energy conversion technologies. A large set of carbon-based ORR electrocatalysts was prepared by a two-step pyrolysis at 600 ◦C and then at 900 ◦C. Gelling sugar, guanidine acetate and cysteine were used as carbon, nitrogen and sulphur sources, respectively; iron and copper salts were utilised to produce non-noble metal-doped carbons. Silica was used as templating agent. The produced materials were thoroughly characterized by means of BET, XPS, XRPD and micro-Raman spectroscopy to investigate their physicochemical properties, and by means of RDE and RRDE methods to study their electrocatalytical properties towards ORR. They consist in sulphur- and/or nitrogen-modified carbons, some of which iron- and/or copper-doped. The massive carbonaceous structure bears bamboo-like C nanotubes onto the surface of iron-containing electrocatalysts. The best ORR electrocatalytic performance pertains to S- and N-modified carbons bearing nanotubes, which points to the occurrence of synergistic effects between heteroatoms and active sites associated to the presence of nanotubes

Graphitization effects induced by thermal treatments of 4H-SiC

4H-SiC is one of the most promising indirect wide-bandgap (3.3 eV) semiconductor for power devices used in the emerging area of high-voltage and high-temperature electronics as well as space and radiation harsh environments applications. The wide diffusion of devices in SiC is related to the high quality of the crystals, both for substrates and epitaxial layers. In this work, we performed thermal treatments in Argon atmosphere at temperatures below 2000°C with the aim to study the thermal stability of substrates of 4H-SiC. The wafer substrates were characterized by micro-Raman spectroscopy, Atomic Force Microscopy and Electrostatic Force Microscopy. The thermal treatments induced inhomogeneity of the wafer surface due to a graphitization process starting from 1600°C

Vulnerability of epitaxial layers and substrates of 4H-SiC to ionizing radiation and thermal treatments

Silicon Carbide (SiC) is a wide-bandgap crystalline semiconductor with an indirect bandgap of 2.3-3.3 eV depending on polytype. 4H-SiC is a very promising semiconductor for high-power devices and high-temperature devices thanks to its superior physical and electrical properties: it exhibits 10 times higher breakdown electric field strength and 3 times higher thermal conductivity than silicon, high chemical inertness, thermal conductivity, mechanical strength, saturation drift velocity [1]. Furthermore, SiC has high radiation hardness thanks to the large values of the threshold energy for defects formation. Consequently, SiC is the most promising semiconductor for fabrication of devices which can operate in extreme conditions, as high levels of irradiation, elevated temperatures, and high chemical activity. Nonetheless, the characteristics of SiC-based devices are influenced by the presence of impurities as well as extended and point defects. In general, the effects of irradiation causes formation of vacancies, interstitials and related defects which may give rise to states in the bandgap influencing the electrical and optical properties of the material [2-3]. Moreover, it has been observed that treatments at temperature of about 2000°C induce the sublimation of Si and the growth of graphene layer on top of SiC in different atmospheres or in vacuum [4-5]. These studies prove the vulnerability of the material. In this work some complementary non-invasive techniques (μ-Raman, steady-state and time resolved photoluminescence spectroscopy) have been used to study the vulnerability of epitaxial layer of 4H-SiC to ionizing radiation (β-rays and X-rays) and to the effects of thermal treatments in a low temperature range (below 2000°C in Ar atmosphere) on substrates of 4H-SiC. The dose range spanned from 1 kGy up to 100 kGy. In the samples irradiated with β-rays the lifetime of the excitonic band decreases when the deposited dose increases. In particular, in the samples with higher native defectiveness the effect starts from lower deposited doses. Conversely, in the samples irradiated with X-rays there aren’t effects at the same deposited dose as β-rays. These findings suggest that irradiation with electrons induces defects related to atomic displacement. The effects of thermal treatments in air, from 100°C up to 900°C, have been explored to study the recovery properties of epitaxial layer of 4H-SiC. The effect of thermal treatments conducted on the substrates were monitored by μ-Raman spectroscopy. Traces of damaged graphene and graphitization have been observed. [1] T. Kimoto P. and J.A. Cooper, Fundamentals of Silicon Carbide Technology. John Wiley & Sons Singapore Pte. Ltd, 2014. [2] A. A. Lebedev et al., Materials Science Forum, 433-436, 2003 [3] A. Le Donne et al., Diamond & Related Materials, 14, 2005 [4] K. V. Emtsev et al., Nature Materials, 8, 203–207, 2009 [5] J. L. Tedesco et al, Appl. Phys. Lett., 96, 222103, 201

Tailored-BODIPY/Amphiphilic Cyclodextrin Nanoassemblies with PDT Effectiveness

Amphiphilic cyclodextrins (aCDs) are an intriguing class of carrier systems which, recently, have been proposed to deliver porphyrinoids and anticancer drugs or combined dose of both for dual therapeutic applications. The design of nanoassemblies based on aCD and photosensitizers (PSs) aims to preserve the photodynamic therapy (PDT) efficacy of PS, reducing the tendency of PS to self-aggregate, without affecting the quantum yield of singlet oxygen (¹O₂) production, and, not less importantly, minimizing dark toxicity and reducing photosensitization effects. With this idea in mind, in this paper, we focus on nanoassemblies between a non-ionic aCD (SC6OH) and halo-alkyl tailored iodinated boron-dipyrromethenes (BODIPY) dye, a class of molecules which recently have been successfully proposed as a stimulating alternative to porphyrinoids for their high photodynamic efficacy. Nanoassemblies of BODIPY/aCD (BL01I@SC6OH) were prepared in different aqueous media by evaporation of mixed organic film of aCD and BODIPY, hydration, and sonication. The nanostructures were characterized, measuring their hydrodynamic diameter and ξ-potential and also evaluating their time-stability in biological relevant media. Taking advantage of emissive properties of the not-iodinated BODIPY analogue (BL01), nanoassemblies based on aCD and BL01 were investigated as model system to get insight on entanglement of BODIPY in the amphiphile in aqueous dispersion, pointing out that BODIPY is well-entrapped in monomeric form (τ ≅ 6.5 ns) within the colloidal carriers. Also morphology and fluorescence emission properties were elucidated after casting the solution on glass. BL01@SC6OH is easily detectable in cytoplasm of HCT116 cell lines, evidencing the remarkable intracellular penetration of this nanoassembly similar to free BODIPY. On the same cell lines, the photodynamically active assembly BL01I/aCD shows toxicity upon irradiation. Despite the fact that free BL01I is more PDT active than its assembly, aCD can modulate the cell uptake of BODIPY, pointing out the potential of this system for in vivo PDT application

Disease activity assessment of rheumatic diseases during pregnancy: a comprehensive review of indices used in clinical studies.

Pregnancy requires a special management in women with inflammatory rheumatic diseases (RDs), with the aim of controlling maternal disease activity and avoiding fetal complications. Despite the heterogeneous course of RDs during pregnancy, their impact on pregnancy largely relates to the extent of active inflammation at the time of conception. Therefore, accurate evaluation of disease activity is crucial for the best management of pregnant patients. Nevertheless, there are limitations in using conventional measures of disease activity in pregnancy, as some items included in these instruments can be biased by symptoms or by physiological changes related to pregnancy and the pregnancy itself may influence laboratory parameters used to assess disease activity. This article aims to summarize the current literature about the available instruments to measure disease activity during pregnancy in RDs. Systemic lupus erythematosus is the only disease with instruments that have been modified to account for several adaptations which might interfere with the attribution of signs or symptoms to disease activity during pregnancy. No modified-pregnancy indices exist for women affected by other RDs, but standard indices have been applied to pregnant patients. The current body of knowledge shows that the physiologic changes that occur during pregnancy need to be either adapted from existing instruments or developed to improve the management of pregnant women with RDs. Standardized instruments to assess disease activity during pregnancy would be helpful not only for clinical practice but also for research purposes

1-Year Outcomes After Transfemoral Transcatheter or Surgical Aortic Valve Replacement: Results From the Italian OBSERVANT Study.

Tamburino C, Barbanti M, D'Errigo P, Ranucci M, Onorati F, Covello RD, Santini F, Rosato S, Santoro G, Fusco D, Grossi C, Seccareccia F; OBSERVANT Research Group. Collaborators (209) Marra S, Marra S, D'Amico M, Gaita F, Moretti C, De Benedictis M, Aranzulla T, Pistis G, Reale M, Bedogni F, Brambilla N, Ferrario M, Ferrero L, Vicinelli P, Colombo A, Chieffo A, Ferrari A, Inglese L, Casilli F, Ettori F, Frontini M, Antona C, Piccaluga E, Klugmann S, De Marco F, Tespili M, Saino A, Leonzi O, Rizzi A, Grisolia E, Franceschini Grisolia E, Isabella G, Fraccaro C, Bernardi G, Bisceglia T, Armellini I, Vischi M, Parodi E, Vignali L, Ardissimo D, Marzocchi A, Marrozzini C, Cremonesi A, Colombo F, Giannini C, Pierli C, Iadanza A, Santoro G, Meucci F, Berti S, Mariani M, Tomai F, Ghini A, Violini R, Confessore P, Crea F, Giubilato S, Sardella G, Mancone M, Ribichini F, Vassanelli C, Dandale R, Giudice P, Vigorito F, Liso A, Specchia L, Indolfi C, Spaccarotella C, Stabile A, Gandolfo C, Tamburino C, Ussia G, Comoglio C, Dyrda O, Rinaldi M, Salizzoni S, Micalizzi E, Grossi C, Di Gregorio O, Scoti P, Costa R, Casabona R, Del Ponte S, Panisi P, Spira G, Troise G, Messina A, Viganò M, Aiello M, Alfieri O, Denti P, Menicanti L, Agnelli B, Donatelli F, Muneretto C, Frontini M, Rambaldini M, Frontini M, Gamba A, Tasca G, Ferrazzi P, Terzi A, Antona C, Gelpi G, Martinelli L, Bruschi G, Graffigna AC, Mazzucco A, Pappalardo A, Gatti G, Livi U, Pompei E, Coppola R, Gucciardo M, Parodi E, Albertini A, Caprili L, Ghidoni I, Gabbieri D, La Marra M, Aquino T, Gherli T, Policlinico S, Di Bartolomeo R, Savini C, Popoff G, Innocenti D, Bortolotti U, Pratali S, Stefano P, Blanzola C, Glauber M, Cerillo A, Chiaramonti F, Pardini A, Fioriello F, Torracca L, Rescigno G, De Paulis R, Nardella S, Musumeci F, Luzi G, Possati G, Bonalumi G, Covino E, Pollari F, Sinatra R, Roscitano A, Chiariello L, Nardi P, Lonobile T, Baldascino F, Di Benedetto G, Mastrogiovanni G, Piazza L, Marmo J, Vosa C, De Amicis V, Speziale G, Visicchio G, Spirito R, Gregorini R, Specchia L, Villani M, Pano MA, Bortone A, De Luca Tupputi Schinosa L, De Cillis E, Gaeta R, Di Natale M, Cassese M, Antonazzo A, Argano V, Santaniello E, Patanè L, Gentile M, Tribastone S, Follis F, Montalbano G, Pilato M, Stringi V, Patanè F, Salamone G, Ruvolo G, Pisano C, Mignosa C, Bivona A, Cirio EM, Lixi G, Seccareccia F, D'Errigo P, Rosato S, Maraschini A, Badoni G, Tamburino C, Santoro G, Santini F, Grossi C, Ranucci M, Covello RD, Fusco D, Onorato F, De Palma R, Scandotto S, Orlando A, Copello F, Borgia P, Marchetta F, Porcu R. BACKGROUND: There is a paucity of prospective and controlled data on the comparative effectiveness of transcatheter aortic valve replacement (TAVR) versus surgical aortic valve replacement (SAVR) in a real-world setting. OBJECTIVES: This analysis aims to describe 1-year clinical outcomes of a large series of propensity-matched patients who underwent SAVR and transfemoral TAVR. METHODS: The OBSERVANT (Observational Study of Effectiveness of SAVR-TAVI Procedures for Severe Aortic Stenosis Treatment) trial is an observational prospective multicenter cohort study that enrolled patients with aortic stenosis (AS) who underwent SAVR or TAVR. The propensity score method was applied to select 2 groups with similar baseline characteristics. All outcomes were adjudicated through a linkage with administrative databases. The primary endpoints of this analysis were death from any cause and major adverse cardiac and cerebrovascular events (MACCE) at 1 year. RESULTS: The unadjusted enrolled population (N = 7,618) included 5,707 SAVR patients and 1,911 TAVR patients. The matched population had a total of 1,300 patients (650 per group). The propensity score method generated a low-intermediate risk population (mean logistic EuroSCORE 1: 10.2 ± 9.2% vs. 9.5 ± 7.1%, SAVR vs. transfemoral TAVR; p = 0.104). At 1 year, the rate of death from any cause was 13.6% in the surgical group and 13.8% in the transcatheter group (hazard ratio [HR]: 0.99; 95% confidence interval [CI]: 0.72 to 1.35; p = 0.936). Similarly, there were no significant differences in the rates of MACCE, which were 17.6% in the surgical group and 18.2% in the transcatheter group (HR: 1.03; 95% CI: 0.78 to 1.36; p = 0.831). The cumulative incidence of cerebrovascular events, and rehospitalization due to cardiac reasons and acute heart failure was similar in both groups at 1 year. CONCLUSIONS: The results suggest that SAVR and transfemoral TAVR have comparable mortality, MACCE, and rates of rehospitalization due to cardiac reasons at 1 year. These data need to be confirmed in longer term and dedicated ongoing randomized trial