420 research outputs found

    A Real-Life Study on the Use of Tildrakizumab in Psoriatic Patients

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    tildrakizumab is a humanized IgG1 kappa monoclonal antibody that selectively targets the p19 subunit of interleukin IL-23, thereby inhibiting the IL-23/IL-17 axis, which is primarily implicated in the immunopathogenesis of psoriasis. Tildrakizumab is approved for the treatment of moderate-to-severe plaque-type psoriasis in adults based on the evidence of two randomized and controlled phase-III clinical trials (reSURFACE 1 and reSURFACE 2). Here, we report our real-life experience treating 53 psoriatic patients (19 female and 34 male) who were administered tildrakizumab every 12 weeks and received follow-ups over 52 weeks. descriptive and inferential statistical analyses were performed, in particular the psoriasis area and severity Index (PASI), dermatology life quality Index (DLQI) and, if applicable, the Nail Psoriasis Severity Index (NAPSI) and Palmoplantar psoriasis physician global assessment (PPPGA). these were assessed at baseline and after different timepoints (weeks) during the follow-up period. we described and evaluated demographical and epidemiological characteristics in our cohort group, focusing on comorbidities. In this group, 35.9% of patients were female and 64.1% were male, with 47.1% being smokers and with a mean age of 51.2 years. a total of 37.7% of these patients was affected by scalp psoriasis; regarding comorbidities, hypertension was the most frequent (32.5%), followed by psoriatic arthritis (PsA) (18.60%) and diabetes (13.9%). at week 52, 93%, 90.2% and 77% of patients achieved a PASI reduction >= 75% (PASI 75), PASI 90 and PASI 100, respectively. In addition, NAPSI, PPPGA and DLQI scores were significantly reduced by week 52. In our cohort of complex psoriasis patients, disease remission began at the end of the fourth week of treatment and remained constant from week 16 to week 52

    α1-Antitrypsin Polymerizes in Alveolar Macrophages of Smokers With and Without α1-Antitrypsin Deficiency

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    BACKGROUND: The deficiency of α1-antitrypsin (AAT) is secondary to misfolding and polymerization of the abnormal Z-AAT in liver cells and is associated with lung emphysema. Alveolar macrophages (AM) produce AAT, however it is not known if Z-AAT can polymerize in AM, further decreasing lung AAT and promoting lung inflammation. AIMS: To investigate if AAT polymerizes in human AM and to study the possible relation between polymerization and degree of lung inflammation. METHODS: Immunohistochemical analysis with 2C1 monoclonal antibody specific for polymerized AAT was performed in sections of: 9 lungs from individuals with AAT deficiency (AATD) and severe COPD, 35 smokers with normal AAT levels of which 24 with severe COPD and 11 without COPD, and 13 non-smokers. AM positive for AAT polymers were counted and expressed as percentage of total AM in lung. RESULTS: AAT polymerization was detected in [27(4-67)%] of AM from individuals with AATD but also in AM from smokers with normal AAT with [24(0-70)%] and without [24(0-60)%] COPD, but not in AM from non-smokers [0(0-1.5)%] (p<0.0001). The percentage of AM with polymerized AAT correlated with pack-years smoked (r=0.53,p=0.0001), FEV1/FVC (r=-0.41,p=0.005), Small Airways Disease (r=0.44,p=0.004), number of CD8+T-cells and neutrophils in alveolar walls (r=0.51,p=0.002; r=0.31,p=0.05 respectively). CONCLUSIONS: Polymerization of AAT in alveolar macrophages occurs in lungs of individuals with AATD but also in smokers with normal AAT levels with or without COPD. Our findings highlight the similarities in the pathophysiology of COPD in individuals with and without AATD, adding a potentially important step to the mechanism of COPD

    Impact of Blood Eosinophil Variability in Asthma:A Real-Life Population Study

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    RATIONALE: Blood eosinophil count predicts response to inhaled corticosteroids and specific biologic therapies in selected asthma patients. Despite this important role, fundamental aspects of eosinophil behavior in asthma have not been studied. Objectives To investigate the behavior of blood eosinophils in a population comparing their distribution with the general population and studying their intra-individual variability over time in relation to hospital episodes (emergency department visits and hospitalizations) in clinical practice. METHODS: The distribution and variability of 35,703 eosinophil determinations in 10,059 stable asthma patients were investigated in the Majorca Real-Life Investigation in COPD and Asthma cohort (MAJORICA). Eosinophil distribution in the asthma population was compared with a control sample from the general population of 8,557 individuals. Eosinophil variability and hospital episodes were analyzed using correlations, ROC curves and multiple regression analysis. We defined the Eosinophil Variability Index (EVI) as (Eosmax-Eosmin/Eosmax) x 100%. The findings of the asthma population were re-tested in an external well-characterized asthma cohort. RESULTS: The eosinophil count values and variability were higher in the asthma population than in the general population (p-value<0.001). Variability data showed a better association with hospital episodes than the counting values. An EVI≥50% was more strongly associated with hospital episodes than any of the absolute counting values. These results were validated in the external cohort. CONCLUSION: The eosinophil variability in asthma patients better identifies the risk of any hospital episode than the absolute counting values currently used to target specific treatments

    Interaction of Pelargonium sidoides Compounds with Lactoferrin and SARS-CoV-2: Insights from Molecular Simulations

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    (1) Background: Pelargonium sidoides extracts and lactoferrin are two important natural, anti-inflammatory, and antiviral agents, which can interfere with the early stages of SARS-CoV-2 infection. Molecular docking and molecular dynamics simulation approaches have been applied to check for the occurrence of interactions of the Pelargonium sidoides compounds with lactoferrin and with SARS-CoV-2 components. (2) Methods: Computational methods have been applied to confirm the hypothesis of a direct interaction between PEL compounds and the lactoferrin protein and between Pelargonium sidoides compounds and SARS-CoV-2 Spike, 3CLPro, RdRp proteins, and membrane. Selected high-score complexes were structurally investigated through classical molecular dynamics simulation, while the interaction energies were evaluated using the molecular mechanics energies combined with generalized Born and surface area continuum solvation method. (3) Results: Computational analyses suggested that Pelargonium sidoides extracts can interact with lactoferrin without altering its structural and dynamical properties. Furthermore, Pelargonium sidoides compounds should have the ability to interfere with the Spike glycoprotein, the 3CLPro, and the lipid membrane, probably affecting the functional properties of the proteins inserted in the double layer. (4) Conclusion: Our findings suggest that Pelargonium sidoides may interfere with the mechanism of infection of SARS-CoV-2, especially in the early stages

    Foliar lead uptake by lettuce exposed to atmospheric fallouts

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    Metal uptake by plants occurs by soil−root transfer but also by direct transfer of contaminants from the atmosphere to the shoots. This second pathway may be particularly important in kitchen gardens near industrial plants. The mechanisms of foliar uptake of lead by lettuce (Lactuca sativa) exposed to the atmospheric fallouts of a lead-recycling plant were studied. After 43 days of exposure, the thoroughly washed leaves contained 335 ± 50 mg Pb kg−1 (dry weight). Micro-X-ray fluorescence mappings evidenced Pb-rich spots of a few hundreds of micrometers in diameter located in necrotic zones. These spots were more abundant at the base of the central nervure. Environmental scanning electron microscopy coupled with energy dispersive X-ray microanalysis showed that smaller particles (a few micrometers in diameter) were also present in other regions of the leaves, often located beneath the leaf surface. In addition, submicrometric particles were observed inside stomatal openings. Raman microspectrometry analyses of the leaves identified smelter-originated Pb minerals but also secondary phases likely resulting from the weathering of original particles. On the basis of these observations, several pathways for foliar lead uptake are discussed. A better understanding of these mechanisms may be of interest for risk assessment of population exposure to atmospheric metal contamination

    Identifying specific causes of kidney allograft loss

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    The causes of kidney allograft loss remain unclear. Herein we investigated these causes in 1317 conventional kidney recipients. The cause of graft loss was determined by reviewing clinical and histologic information the latter available in 98% of cases. During 50.3 ± 32.6 months of follow-up, 330 grafts were lost (25.0%), 138 (10.4%) due to death with function, 39 (2.9%) due to primary nonfunction and 153 (11.6%) due to graft failure censored for death. The latter group was subdivided by cause into: glomerular diseases (n = 56, 36.6%); fibrosis/atrophy (n = 47, 30.7%); medical/surgical conditions (n = 25, 16.3%); acute rejection (n = 18, 11.8%); and unclassifiable (n = 7, 4.6%). Glomerular pathologies leading to failure included recurrent disease (n = 23), transplant glomerulopathy (n = 23) and presumed nonrecurrent disease (n = 10). In cases with fibrosis/atrophy a specific cause(s) was identified in 81% and it was rarely attributable to calcineurin inhibitor (CNI) toxicity alone (n = 1, 0.7%). Contrary to current concepts, most cases of kidney graft loss have an identifiable cause that is not idiopathic fibrosis/atrophy or CNI toxicity. Glomerular pathologies cause the largest proportion of graft loss and alloinmunity remains the most common mechanism leading to failure. This study identifies targets for investigation and intervention that may result in improved kidney transplantation outcomes
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