Effectiveness and safety of bimekizumab for the treatment of plaque psoriasis. a real-life multicenter study—IL PSO (Italian landscape psoriasis)

Introduction: Bimekizumab is a monoclonal antibody that targets Interleukin-17 A and F, approved for the treatment of moderate-to-severe plaque psoriasis. While bimekizumab has been evaluated in several phase-III clinical trials, real-world evidence is still very limited. Method: This multicenter retrospective study included patients affected by plaque psoriasis treated with bimekizumab from May 1, 2022 to April 30, 2023, at 19 Italian referral hospitals. Patients affected by moderate-to-severe plaque psoriasis eligible for systemic treatments were included. The effectiveness of bimekizumab was evaluated in terms of reduction in psoriasis area and severity index (PASI) compared with baseline at weeks 4 and 16. The main outcomes were the percentages of patients achieving an improvement of at least 75% (PASI75), 90% (PASI90) and 100% (PASI100) in PASI score. Results: The study included 237 patients who received at least one injection of bimekizumab. One hundred and seventy-one patients and 114 reached four and 16 weeks of follow-up, respectively. Complete skin clearance was achieved by 43.3% and 75.4% of patients at weeks 4 and 16, respectively. At week 16, 86.8% of patients reported no impact on their quality of life. At week 16, there were no significant differences between bio-naïve and bio-experienced patients in terms of PASI75, PASI90 and PASI100. The most commonly reported adverse events (AEs) were oral candidiasis (10.1%). No severe AEs or AEs leading to discontinuation were observed throughout the study. Conclusion: Our experience supports the effectiveness and tolerability of bimekizumab in a real-world setting with similar results compared with phase-III clinical trials

Exposure to novel coronavirus in patients on renal replacement therapy during the exponential phase of COVID-19 pandemic: survey of the Italian Society of Nephrology

Background: Between February and April 2020, Italy experienced an overwhelming growth of the COVID-19 pandemic. Little is known, at the country level, where and how patients on renal replacement therapy (RRT) have been mostly affected. Methods: Survey of the network of Nephrology centers using a simplified 17 items electronic questionnaire designed by Italian Society of Nephrology COVID-19 Research Group. We used spatial epidemiology and geographical information systems to map SARS-CoV-2 spread among RRT patients in Italy. Results: On April 9th 2020, all nephrology centers (n = 454) listed in the DialMap database were invited to complete the electronic questionnaire. Within 11 days on average, 365 centers responded (80.4% response rate; 2.3% margin of error) totaling 60,441 RRT patients. The surveyed RRT population included 30,821 hemodialysis (HD), 4139 peritoneal dialysis (PD), and 25,481 transplanted (Tx) patients respectively. The proportion of SARS-CoV-2 positive RRT patients in Italy was 2.26% (95% CI 2.14\u20132.39) with significant differences according to treatment modality (p < 0.001). The proportion of patients positive for SARS-CoV-2 was significantly higher in HD (3.55% [95% CI 3.34\u20133.76]) than PD (1.38% [95% CI 1.04\u20131.78] and Tx (0.86% [95% CI 0.75\u20130.98]) (p < 0.001), with substantial heterogeneity across regions and along the latitude gradient (p < 0.001). In RRT patients the highest rate was in the north-west (4.39% [95% CI 4.11\u20134.68], followed by the north-east (IR 2.06% [1.79\u20132.36]), the center (0.91% [0.75\u20131.09]), the main islands (0.67% [0.47\u20130.93]), and the south (0.59% [0.45\u20130.75]. During the COVID-19 pandemic, among SARS-Cov-2 positive RRT patients the fatality rate was 32.8%, as compared to 13.3% observed in the Italian population as of April 23rd. Conclusions: A substantial proportion of the 60,441 surveyed RRT patients in Italy were SARS-Cov-2 positive and subsequently died during the exponential phase of COVID-19 pandemic. Infection risk and rates seems to differ substantially across regions, along geographical latitude, and by treatment modality

Effect of Grape Pomace Polyphenols With or Without Pectin on TMAO Serum Levels Assessed by LC/MS-Based Assay: A Preliminary Clinical Study on Overweight/Obese Subjects

Growing evidence suggests that trimethylamine N-oxide (TMAO) is recognized as a biomarker of increased cardiovascular risk. So far, the evaluation of TMAO serum levels in the clinical practice is limited due to the lack of developing new facile methods with reduced limitations. However, few approaches were achieved to determine TMAO in serum by using mass spectrometry-based technique, some limitations were reported including the use of internal standards. Therefore, in this work, a liquid chromatography-mass spectrometry (LC/MS) based-assay was developed to evaluate the effect of grape pomace extract (Taurisolo®, group A) or Taurisolo®+pectin (group B) on TMAO serum levels in a cohort of overweight/obese subjects. The serum levels of TMAO have been assessed before and after treatment, through LC/MS analysis. After 8-week treatment, in both intervention groups TMAO serum levels significantly decreased (-78.58% p = 0.006 and -76.76% p = 0.001, group A and group B, respectively). Moreover, we performed several analyses aimed to validate the LC/MS method we used. The method has high precision (% C.V = from 12.12 to 3.92% and from 8.25 to 1.07% for intraday and interday, respectively) and accuracy (% bias = from -5.52 to 0.5% and from -1.42 to 3.08% for intraday and interday, respectively). TMAO recoveries from serum ranged from 99 to 97%; LOD: 2 ng/ml and LOQ: 6 ng/ml. In conclusion, we demonstrated the efficacy of a novel nutraceutical formulation in reducing TMAO serum levels in high cardiovascular risk-subjects, and proposed a useful, versatile and rapid LC/MS method for identification and quantization of TMAO, without the use of marked/isotopic internal standards. It, thus, may represent a novel and practical method with applications in clinical practice and nutraceutical research.Clinical Trial Registration: This study is listed on the ISRCTN registry with ID ISRCTN10794277 (doi: 10.1186/ISRCTN10794277)

Discontinuation of first-line bevacizumab in metastatic colorectal cancer: the BEAWARE Italian Observational Study

BEAWARE investigated the pattern of first-line bevacizumab early interruption in the Italian real-world setting of metastatic colorectal cancer

Taurisolo®, a novel nutraceutical formulation based on grape pomace polyphenols, as a tool for the management of oxidative stress- and atherosclerosis-related diseases

The present PhD thesis summarises evidence from all the studies performed during the three-year PhD Course in Pharmaceutical Science, at the NutraPharmaLabs of the Department of Pharmacy, University of Naples Federico II, having as mail goal the evaluation of the nutraceutical potential of Taurisolo®, a novel nutraceutical formulation based on grape pomace polyphenolic extract. In particular, the present PhD project has been conducted in cooperation with both industrial (MBMed Company, Turin, Italy) and foreign University (University of Balearic Islands, Palma del Mallorca, Spain) partners. The entire project was planned with a dual view: design and formulate a novel nutraceutical product starting from re-use of agri-food by-products, following all the steps required by the nutraceutical industry, including preventive characterisation of the chemical profile, evaluation of bioaccessibility and bioavailability of bioactive compounds, optimisation of the productive processes and their translation in large-scale, marketing techniques evaluation of the biological activities, following a pharmacological approach including pre-clinical and clinical studies. More specifically, results herein presented refer to all the studies performed in our Labs and in collaboration with other Departments and Research Institutes. They include in vitro studies, animal-based studies and randomised clinical trials conducted on both healthy and pathological subjects. Further studies are still ongoing with the aim to clarify the main putative mechanisms of action for the cardioprotective role played by Taurisolo® or to provide novel insight regarding the observed clinical results. In summary, data so far collected allow concluding that Taurisolo® is a useful and valid polyphenol-based formulation with promising nutraceutical properties in reduction of risk factors related to both development and progression of cardiovascular diseases, in particular atherosclerosis

Formulation of novel Functional Foods and Nutraceutical Products from Annurca apple with healthy human effects

The present thesis work aimed to the in vitro and in vivo evaluation of the nutraceutical potential of whole fruit or only of its polyphenolic fraction mainly obtained from a specific apple Malus pumila Miller cv Annurca. This apple fruit is used in various manners, the whole fruit is enabled to produce a functional food, while the polyphenolic extract is used to design and project different nutraceutical formulations and vegetal extract innovative using as potential medical device. Various healthy human bioactivities of Annurca apple formulations have been investigated, from the cholesterol-lowering effect, atherosclerosis prevention to anticancer activity. Particularly, the whole fruit Annurca apple is used to the preparation of probiotic apple puree, a probiotic juice, with various purposes: no dairy probiotic product, with higher bioaccessibility (percentage increases of 40.12% of TC, and of 11.89%of antioxidant activity) and consequently higher bioavailability of phenolic compounds than in simple puree. Additionally preliminary in vivo study, has shown a reduction of TMAO blood levels (63,12%), due to the combined effects of probiotic and Annurca apple polyphenols daily intake. Industrial scale-up of row lab scale polyphenolic Annurca apple extract, resulting in two products AMS (polyphenolic extract microencapsulated with maltodextrins (400mg)) and AMSbz (polyphenolic extract microencapsulated with maltodextrins (400 mg), biotin (0.20 mg), selenomethionine (80.0 µg), and zinc acetate (21.0 mg)). From randomized clinical trial, was obtained on average, after two months of treatment a % increase of hairs growth, weight and keratin content by 118.3, 37.3, and 35.7%. After, in vitro treatment of HaCaT cells (human keratinocyte cell line) increased the keratin expression of three fold against the control. These effects are ascribable a dimeric procyanidin. The same compound is responsible of interaction at duodenal level, with intestinal micelle, particularly interacting with phosphatidylcholine determine a breakage micellar system, causing the cholesterol precipitation, limiting its intestinal absorption. Finally, lab and industrial scale of polyphenolic Annurca apple extracts were tested on in vitro cultures of cells carrying FAP (Familial Adenomatous Polyposis) mutations and on ex vivo biopsies of FAP patients, the WNT inhibitory activity of Annurca was studied. Duodenal digested apple extract has shown no inhibitory activity on WNT pathway, the signaling via responsible of FAP, but stronger inhibitory activity has been shown by industrial-scale product, based on another apple cultivar named “Limoncella” Malus Domestica cv Limoncella. This effect was ascribable to the quercetin content of Limoncella’s industrial product higher than the equivalent Annurca version

Análise da viabilidade da criação de um Boutique Hotel nas Caldas da Rainha

O presente Plano de Negócios visa analisar a viabilidade económica e financeira da abertura de um Boutique Hotel na cidade de Caldas da Rainha, num edifício histórico no centro da mesma, e em que se pretende efetuar obras de reabilitação para a sua renovação. Tendo em consideração a importância que o setor do turismo apresenta não só no país, como também na região Centro, o objetivo principal deste projeto visa o desenvolvimento da região, bem como criar um estímulo financeiro e social à cidade em causa, com a criação de emprego e de um espaço atrativo na mesma. Com este projeto pretende-se não só aumentar a oferta disponível na região, especialmente no segmento de luxo, mas também oferecer aos cidadãos caldenses um local onde possam estar e usufruir de um espaço em que impera a familiaridade. O principal objetivo do projeto é oferecer um serviço de qualidade numa zona histórica da cidade e que se encontra subaproveitada, aumentando o interesse da população local, bem como dos turistas que a visitem. Com um investimento inicial de cerca de 1 milhão de euros, financiado através de um empréstimo bancário e de capitais próprios. Numa análise a 10 anos, as vendas ultrapassarão os 900.000€, entre vendas de alojamento, de refeições, eventos e workshops. O projeto apresenta um Valor Atual Líquido (VAL) de 933.103€, com uma Taxa Interna de Rentabilidade (TIR) de 31,47% e um Payback Period (PP) de 5 anos.This Business Plan intends to evaluate the economic and financial viability of opening a Boutique Hotel in the city of Caldas da Rainha, in an historic building located in the city center, where it is intended to have some rehabilitation works for its renovation. Considering the importance of the touristic sector, not only to the country, but also to the Center region, the main goal of this project is to help developing the region, as well as to create a financial and social incentive do the city, with emploment creation and by creating an atractive place in the city. The aim of this project is to increase the existing accommodation offer, especially in the luxury segment, but also to offer locals a place where they can go and experience a distinctive venue. The main goal of this project is to offer a quality service in an historic part of the city, which is at the moment under utilised, increasing the local populations’ interest, as well as the tourists’ interest in visiting it. With an initial investment of around 1 million euros, financed with a bank load and own funds. In a 10 year analysis, sales will exceed the 900.000€, between accommodation, meals, events and workshops. This project presents a Net Present Value (NPV) of 933.103, an Internal Rate of Return (IRR) of 31,47% and a Payback Period (PP) of 5 years

Nutraceutical potential of vegetal food products typical of Campania region: Mela Annurca Campana IGP

The nutraceutical potential of a specific apple cultivar, “Annurca”, was evaluated by both in vitro and in vivo studies. Particularly, the effects of Annurca polyphenolic extract on lipid uptake and metabolism were evaluated and compared with those obtained from polyphenolic extracts coming from other conventional cultivars. In vitro experiments performed on HepG2 (human hepatocellular liver carcinoma) cells indicated Annurca flesh polyphenolic extract as the most active in reducing cholesterol and triglyceride uptake (about, 15 and 20 times than control cells, respectively), in inhibiting lipase activity (-55% than control cells), in enhancing low-density lipoprotein (LDL) receptor binding activity (+46% than control cells), in increasing Apolipoprotein A1 (ApoA1) cell expression (+71.4% above control levels) and in protecting from oxidative stress (cell proliferation: +47.5%; cell radical levels: -33.3% than control cells). All the amazing in vitro properties of Annurca flesh polyphenolic extract were attributed to its high content in procyanidins, and good linear correlations between procyanidin content and cellular effects were registered. In vitro experiments of gastrointestinal digestion showed a good bioaccessibility of apple procyanidins during the three digestive steps. After salivary digestion, their bioaccessibility was 35% of undigested samples, suggesting a potential good absorption through the oral mucosa, and it increased during gastric (+5.1% compared to salivary digestion) and intestinal (+16% in respect to gastric digestion) phases. However, their bioavailability was very low (6.7% of their native pattern and 12.0% of the intestinal digestion), suggesting they would act mainly in the gut. The small portion absorbed was strongly bound to plasma proteins (93.4%), especially to high-density lipoproteins (HDLs, 58.7%), suggesting a role in cholesterol metabolism. The results of the first clinical trial showed that Annurca apple was the most effective, since it decreased total cholesterol (TC, -8.4%) and low-density lipoprotein cholesterol (LDL-C, -14.5%) levels, and raised high-density lipoprotein cholesterol levels (HDL-C, +14.0%). The results of the second clinical trial showed that the treatment with AppleMetS™ (AMS) resulted in a significant decrease in plasma LDL-C levels (-37.5%), an effect comparable to that obtained after treatment with 40 mg of simvastatin or 10 mg of atorvastatin. Moreover, it increased HDL-C levels of about 49.2%, an effect never observed in any pharmaceutical or nutraceutical substance. These amazing results suggested that Annurca polyphenols represent an important tool for the treatment of mild hypercholesterolemia, especially in elderly people with higher values of baseline total cholesterol

Hyperbaric oxygen therapy conoscenze ed esigenze formative degli infermieri dei centri iperbarici italiani: studio osservazionale

Scopo dello studio: Lo scopo dello studio è quello di fotografare lo status infermieristico nei centri iperbarici italiani e indagare quali conoscenze ed esigenze formative emergono dagli infermieri che svolgono attività diretta in camera iperbarica, o che operano in attività di supporto all’ossigenoterapia. Materiali e metodi: Lo strumento utilizzato per la raccolta dei dati è un questionario appositamente strutturato per lo studio. Lo strumento presenta 47 domande di cui 44 a risposte chiuse e 3 a risposte semiaperte. I centri iperbarici italiani che attualmente svolgono ossigenoterapia iperbarica sono 64 e di questi 63 sono stati considerati nello studio, con una finestra di raccolta dati di 90 giorni (giugno, luglio e agosto). Le strutture che hanno risposto sono state n.51 centri iperbarici (81,0%), n.4 centri non hanno partecipato (6,3%), n.8 non presentano infermieri (12,7%) e n.1 è stato escluso dal campione, per un totale di 149 questionari compilati. Risultati: Il campione analizzato presenta una età media di 46,9 anni (σ=9,6), a maggioranza femminile (50,3%), un diploma professionale regionale (60,4%), una media di 23,1 anni (σ=10,9) di attività infermieristica di cui 10,9 anni (σ=6,8) in ambito iperbarico, proveniente per il 75,2% da un reparto ospedaliero. Il 49,0% del campione ha partecipato ad un corso interno al proprio centro sull’ambiente straordinario. Le conoscenze di argomenti specifici sono mediamente buone, ma la maggioranza ritiene utile acquisire approfondimenti su specifiche tematiche, inclusa la partecipazione ad un master universitario in ambito iperbarico (54,4%). Conclusioni: La medicina iperbarica è una disciplina medica giovane ed emergente nella quale gli attuali infermieri sono presenti in media da una decina d’anni. La disomogeneità di preparazione nel campo dev’essere colmata con corsi strutturati e possibilmente accademici. Esigenze di approfondimenti su specifiche tematiche emergono dagli infermieri stessi che praticano quotidianamente attività nell’ambiente straordinari