Archivio Istituzionale della Ricerca - Università degli Studi della Campania "Luigi Vanvitelli"
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Biologics as well as inhaled anti-asthmatic therapy achieve clinical remission: Evidence from the Severe Asthma Network in Italy (SANI)
No full textBackground: This study aimed to evaluate the impact of severe asthma (SA) treatments after 12 months in achieving clinical remission (CR) within the context of the Severe Asthma Network in Italy (SANI) using the recent SANI definition of CR on treatment. Methods: CR has been defined by SANI as complete, partial, and no CR. Complete CR is defined by the absence of oral corticosteroids (OCS), no symptoms, no exacerbations, and stable lung function, and partial CR requires the absence of OCS and the fulfillment of 2 out of the other 3 criteria. Patients who do not meet the previous criteria do not reach CR. Results: After 12 months of treatment, 283 patients were selected to evaluate the effectiveness of biologics (225 patients) and inhaled therapy (58 patients) in achieving CR. Among patients treated with biologic agents, 45.8% reached complete CR, 23.1% partial CR, and 31.1% no CR. Differences in CR achievement according to type of biologic agent administered were observed. Interesting results were found when assessing the inhaled therapy (ICS/LABA/LAMA and no biologics) effectiveness: 34.5% patients reached complete CR, 34.5% partial CR, and 31.0% did not reach CR. This finding is noteworthy since it further supports the efficacy of inhaled treatment in certain SA patients and highlights the relevance of using CR as a modern outcome of SA treatments. Chronic rhinosinusitis with nasal polyps (CRSwNP) comorbidity was associated, though not significantly, with CR achievement in patients treated with biologics. Asthma Control Test (ACT) and Asthma Control Questionnaire (ACQ) scores significantly impacted CR (p = 0.003 and p = 0.027, respectively), while biomarkers, namely IgE, blood eosinophils, or fractional exhaled nitric oxide (FeNO), were not associated with CR achievement. Conclusions: This study confirmed the effectiveness of biologics in reaching CR and demonstrated also inhaled therapies able to achieve CR. These innovative findings should encourage post hoc analysis of randomized clinical trials or even retrospective analysis of SA patient cohorts to evaluate CR with different inhaled treatments and further define the populations eligible for each treatment. Trial registration: ClinicalTrials.gov ID: NCT06625216; Central Ethics Committee: Comitato Etico Area Vasta Nord-Ovest Toscana (study number 1245/2016, protocol number:73714)
Identifying Metabolomic Mediators of the Physical Activity and Colorectal Cancer Relationship
No full textBackground: Current evidence suggests higher physical activity (PA) levels are associated with a reduced risk of colorectal cancer. However, the mediating role of the circulating metabolome in this relationship remains unclear. Methods: Targeted metabolomics data from 6,055 participants in the European Prospective Investigation into Cancer and Nutrition cohort were used to identify metabolites associated with PA and derive a metabolomic signature of PA levels. PA levels were estimated using the validated Cambridge PA index based on baseline questionnaires. Mediation analyses were conducted in a nested case–control study (1,585 cases, 1,585 controls) to examine whether individual metabolites and the metabolomic signature mediated the PA–colorectal cancer association. Results: PA was inversely associated with colorectal cancer risk (OR per category change: 0.90, 95% confidence interval, 0.83–0.97; P value 1⁄4 0.009). PA levels were associated with 24 circulating metabolites after FDR correction, with the strongest associations observed for phosphatidylcholine acyl-alkyl (PC ae) C34:3 (FDR-adjusted P value 1⁄4 1.18 X 10-10) and lysophosphatidylcholine acyl C18:2 (FDR-adjusted P value 1⁄4 1.35 X 10-6). PC ae C34:3 partially mediated the PA–colorectal cancer association (natural indirect effect: 0.991, 95% confidence interval, 0.982–0.999; P value 1⁄4 0.04), explaining 7.4% of the association. No mediation effects were observed for the remaining metabolites or the overall PA metabolite signature. Conclusions: PC ae C34:3 mediates part of the PA–colorectal cancer inverse association, but further studies with improved PA measures and extended metabolomic panels are needed. Impact: These findings provide insights into PA-related biological mechanisms influencing colorectal cancer risk and suggest potential targets for cancer prevention interventions
Il diritto civile nella legalità costituzionale. L'opera di Pietro Perlingieri
No full textIl volume raccoglie gli atti di un Convegno di studi organizzato, nei giorni 6 e 7 ottobre 2022, presso il Dipartimento di Giurisprudenza dell’Università degli Studi di Napoli Federico II, per presentare la quarta edizione dell’opera «Il diritto civile nella legalità costituzionale secondo il sistema italo-europeo delle fonti» di Pietro Perlingieri. I contributi testimoniano, con varietà di accenti e sfumature, l’evoluzione di un pensiero giuridico che dalla seconda metà del secolo scorso rappresenta un autentico Manifesto culturale della civilistica italiana
Continuous flow synthesis of gamma-glutamyl peptides using GGT adsorbed on hydroxyapatite
No full textDespite the many advantages presented by enzyme-catalysed reactions, their implementation at industrial level is hampered due to protein’s poor long-term stability under harsh conditions and difficult separation from the reaction mixture and consequently reuse. To address these problems, the immobilisation of the enzyme on an insoluble support is a possible solution. This strategy, in combination with continuous flow technologies, can lead to process intensification.
In the pursuit of a more sustainable Chemistry, the research of the last years has been devoted to find greener alternatives compared to petro-based support usually employed in enzyme immobilisation. Among these, hydroxyapatite (HAP), the mineral component of mammalian bones, represents a suitable candidate thanks to its structural stability, non-toxicity, large surface area and ease of surface modification. Moreover, it can also be derived from waste such as ashes from waste-to-energy plants, the fish supply chain, the avian supply chain, etc., in agreement with circular economy principles.
Gamma-Glutamyl transferase from Escherichia coli (EcGGT) was chosen as the model enzyme to study the immobilisation process on HAP. Enzyme immobilisation was carried out by adsorption, simply by mixing an enzyme solution and a hydroxyapatite suspension under controlled conditions (pH, temperature). Different particle sizes and experimental set-ups were investigated and, after assessing that the enzyme did not desorb under reaction conditions, the supported GGT was tested as biocatalysts in the enzymatic synthesis of gamma-L-glutamyl-S-allyl-L-cysteine, a natural compound with flavour-enhancer properties. The enzyme reusability was tested and its storage stability was verified. After assessing the applicability of the HAP-adsorbed GGT in batch conditions, the same enzyme was adsorbed in continuous flow conditions in a packed-bed reactor made of HAP. Different residence times were studied, and the obtained reactor was used in the same model reaction (Figure 1).
Figure 1. Continuous flow synthesis of gamma-L-glutamyl-S-allyl-L-cystein
Patient-specific factors, patient preference, and nodule size as implications in the initial surgery of high risk indeterminate thyroid nodules
No full textPurpose: To evaluate the frequency of total thyroidectomy (TT) for thyroid nodules cytologically classified as high-risk indeterminate (TIR3B) and to explore the impact of patient specific factors (PSFs) (some clinical variables) associated with TT for follicular thyroid carcinoma (FTC). Moreover, we aim to investigate the nodule size as a factor influencing the risk of malignancy (ROM) and the risk of aggressiveness of FTC. Methods: We retrieved consecutive FTC cases, and an equal number of follicular adenoma (FA) from adult patients with TIR3B thyroid nodules, which were operated in our Academic referral center between March 1, 2018, and December 31, 2024. Results: We reviewed 112 TIR3B thyroid nodules, histologically subdivided into 56 FTC cases and 56 FA cases. TT was performed in 83% of cases. PSFs were present in 47.4% of patients undergoing hemithyroidectomy (HT) and in 61.3% of patients undergoing TT. No statistical significance was found for PSFs as predictors of TT. For the 30 mm ≤ dmax <40 mm size category we found an odds ratio (OR) of 2.0 [1.101; 3.551] (p-value 0.022) for risk of FTC. We found the existence of a positive relationship between dimensions of FTC and its aggressiveness. Conclusion: TT was largely performed as initial surgery for TIR3B thyroid nodules. PSFs and patient preferences should be explored when planning the initial surgical management of a nodule with TIR3B cytology. Large nodule size (30 ≤ dmax < 40) can be integrated into decision making for patients with a cytology of TIR3B, since it increases the risk of FTC. Larger FTC seems to be more aggressive
PCSK9 Inhibitors “Fast Track” Use Versus “Stepwise” Lipid-Lowering Therapy in Patients with Acute Coronary Syndrome: A Retrospective Single-Center Study in a “Real-World” Population
No full textBackground: The “fast track” addition (within 48 h) of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) to the optimized oral lipid-lowering therapy (LLT) during hospitalization for acute coronary syndrome (ACS) has been shown to rapidly achieve the low-density lipoprotein cholesterol (LDL-C) therapeutic targets. However, so far, its efficacy in real-world settings remains understudied. Methods: We retrospectively analyzed 128 ACS patients treated at our center, comparing “PCSK9i fast track” use within 48 h to standard “stepwise” LLT. Lipid levels and incidence of major adverse cardiovascular events (MACEs) were evaluated at 30 and 180 days. Results: The “PCSK9i fast track” group achieved significantly lower LDL-C levels at 30 days (41.5 ± 27.5 vs. 85.6 ± 35.9 mg/dL, p < 0.001) and 180 days (29.6 ± 21.0 vs. 59.0 ± 32.4 mg/dL, p < 0.001). Recommended LDL-C targets (<55 mg/dL) were met by 88.3% of the “PCSK9i fast track” group at 180 days, compared with 61.9% of controls (p < 0.001). No significant differences in MACEs were observed between groups. No adverse effects from PCSK9i use were noted. Conclusions: The “PCSK9i fast track” strategy was safe and effective in achieving LDL-C targets more rapidly than conventional approaches in real-world ACS patients