Publications by authors named "Giuseppe D"

111 Publications

Investigation of the association between coffee and risk of RA-results from the Swedish EIRA study.

Authors:
Helga Westerlind Justine Dukuzimana Xiaomin Lu Lars Alfredsson Lars Klareskog Daniela Di Giuseppe

Arthritis Res Ther 2022 07 26;24(1):178. Epub 2022 Jul 26.

Clinical Epidemiology Division, Department of Medicine, Karolinska Institutet, Solna, Sweden.

Background: Studies on the association between coffee, a modifiable lifestyle factor, and rheumatoid arthritis (RA), a chronic autoimmune disease primarily affecting the joints, have been conflicting. The aim of the present study was to study the association between coffee consumption and risk of RA in the context of different lifestyle factors.

Methods: We included 2184 cases (72% women, mean age 55 years) newly diagnosed with RA during 2005-2018 in Sweden and 4201 controls matched on age, sex, and residential area. Data on coffee consumption was collected through a food frequency questionnaire and categorized into < 2 (reference), 2-< 4, 4-< 6, and ≥ 6 cups/day. We calculated odds ratios (OR) with 95% confidence intervals (CI) for coffee consumption and risk of RA, in a crude model (taking matching factors into account), and then adjusted first for smoking and further for BMI, educational level, alcohol consumption, and physical activity. We also stratified analyses on sex, smoking, rheumatoid factor, and anti-CCP2 status.

Results: In the crude model, high coffee consumption was associated with increased risk of RA (OR = 1.50, 95% CI 1.20-1.88 for ≥ 6 cups/day compared to < 2 cups). After adjusting for smoking, the OR decreased and was no longer statistically significant (OR = 1.16, 95% CI 0.92-1.46) and decreased further in the full model (OR = 1.14 95% CI 0.89-1.45). This pattern held true in all strata.

Conclusion: The findings from this large, population-based case-control study did not support a significant association between coffee consumption and risk of RA as a whole nor within different subgroups.
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http://dx.doi.org/10.1186/s13075-022-02862-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9317433PMC
July 2022

Development of a Prediction Model for COVID-19 Acute Respiratory Distress Syndrome in Patients With Rheumatic Diseases: Results From the Global Rheumatology Alliance Registry.

Authors:
Zara Izadi Milena A Gianfrancesco Alfredo Aguirre Anja Strangfeld Elsa F Mateus Kimme L Hyrich Laure Gossec Loreto Carmona Saskia Lawson-Tovey Lianne Kearsley-Fleet Martin Schaefer Andrea M Seet Gabriela Schmajuk Lindsay Jacobsohn Patricia Katz Stephanie Rush Samar Al-Emadi Jeffrey A Sparks Tiffany Y-T Hsu Naomi J Patel Leanna Wise Emily Gilbert Alí Duarte-García Maria O Valenzuela-Almada Manuel F Ugarte-Gil Sandra Lúcia Euzébio Ribeiro Adriana de Oliveira Marinho Lilian David de Azevedo Valadares Daniela Di Giuseppe Rebecca Hasseli

ACR Open Rheumatol 2022 Jul 22. Epub 2022 Jul 22.

Justus-Liebig University Giessen, Campus Kerckhoff, Giessen, Germany.

Objective: Some patients with rheumatic diseases might be at higher risk for coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS). We aimed to develop a prediction model for COVID-19 ARDS in this population and to create a simple risk score calculator for use in clinical settings.

Methods: Data were derived from the COVID-19 Global Rheumatology Alliance Registry from March 24, 2020, to May 12, 2021. Seven machine learning classifiers were trained on ARDS outcomes using 83 variables obtained at COVID-19 diagnosis. Predictive performance was assessed in a US test set and was validated in patients from four countries with independent registries using area under the curve (AUC), accuracy, sensitivity, and specificity. A simple risk score calculator was developed using a regression model incorporating the most influential predictors from the best performing classifier.

Results: The study included 8633 patients from 74 countries, of whom 523 (6%) had ARDS. Gradient boosting had the highest mean AUC (0.78; 95% confidence interval [CI]: 0.67-0.88) and was considered the top performing classifier. Ten predictors were identified as key risk factors and were included in a regression model. The regression model that predicted ARDS with 71% (95% CI: 61%-83%) sensitivity in the test set, and with sensitivities ranging from 61% to 80% in countries with independent registries, was used to develop the risk score calculator.

Conclusion: We were able to predict ARDS with good sensitivity using information readily available at COVID-19 diagnosis. The proposed risk score calculator has the potential to guide risk stratification for treatments, such as monoclonal antibodies, that have potential to reduce COVID-19 disease progression.
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http://dx.doi.org/10.1002/acr2.11481DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9350083PMC
July 2022

Is the risk of infection higher during treatment with secukinumab than with TNF-inhibitors? An observational study from the Nordic countries.

Authors:
Bente Glintborg Daniela Di Giuseppe Johan K Wallman Sella A Provan Dan Nordström Anna-Mari Hokkanen Jenny Österlund Eirik Kristianslund Tore K Kvien Bjorn Gudbjornsson Merete Lund Hetland Brigitte Michelsen Lennart Jacobsson Johan Askling Ulf Lindström

Rheumatology (Oxford) 2022 Jun 20. Epub 2022 Jun 20.

Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.

Objectives: The positioning of secukinumab in the treatment of axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) is debated, partly due to a limited understanding of the comparative safety of available treatments. We aimed to assess risk of the key safety outcome infections, during treatment with secukinumab and tumor necrosis factor inhibitors (TNFi).

Methods: Patients with SpA and PsA starting secukinumab or TNFi year 2015 through 2018 were identified in four Nordic rheumatology registers. The first hospitalized infection during the first year of treatment was identified through linkage to national registers. Incidence rates (IR) with 95% confidence intervals per 100 patient-years were calculated. Adjusted hazard ratios (HR) were estimated through Cox regression, with secukinumab as reference. Several sensitivity analyses were performed to investigate confounding by indication.

Results: Among 7708 patients with SpA and 5760 patients with PsA, we identified 16229 treatment courses of TNFi (53% bionaïve) and 1948 with secukinumab (11% bionaïve). For secukinumab, the first-year risk of hospitalized infection was 3.5% (IR 5.0; 3.9-6.3), compared with 1.7% (IR 2.3; 1.7-3.0) during 3201 courses with adalimumab, with the IRs for other TNFi in between. The adjusted HR for adalimumab, compared with secukinumab was 0.58 (0.39-0.85). In sensitivity analyses, the difference with secukinumab was somewhat attenuated and in some analyses no longer statistically significant.

Conclusion: When used according to clinical practice in the Nordic countries, the observed first-year absolute risk of hospitalized infection was doubled for secukinumab compared with adalimumab. This excess risk seemed largely explained by confounding by indication.
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http://dx.doi.org/10.1093/rheumatology/keac358DOI Listing
June 2022

Fever following Covid-19 vaccination in subjects with Brugada syndrome: Incidence and management.

Authors:
Francesco Santoro Pasquale Crea Pier Luigi Pellegrino Rosa Cetera Domenico Gianfrancesco Mohammad Abumayyaleh Dattilo Giuseppe Marta Allegra Nastasia Mancini Girolamo D'Arienzo Andreas Mȕgge Assem Aweimer Francesco Bartolomucci Ibrahim Akin Ibrahim El-Battrawy Natale Daniele Brunetti

J Cardiovasc Electrophysiol 2022 Jun 13. Epub 2022 Jun 13.

Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy.

Background: Fever is a potential side effect of the Covid-19 vaccination. Patients with Brugada syndrome (BrS) have an increased risk of life-threatening arrhythmias when experiencing fever. Prompt treatment with antipyretic drugs is suggested in these patients.

Aim Of The Study: To evaluate the incidence and management of fever within 48 h from Covid-19 vaccination among BrS patients.

Methods: One hundred sixty-three consecutive patients were enrolled in a prospective registry involving five European hospitals with a dedicated inherited disease ambulatory.

Results: The mean age was 50 ± 14 years and 121 (75%) patients were male. Prevalence of Brugada electrocardiogram (ECG) pattern type-1, -2, and -3 was 32%, 44%, and 24%, respectively. Twenty-eight (17%) patients had an implantable cardioverter-defibrillator (ICD). Fever occurred in 32 (19%) BrS patients after 16 ± 10 h from vaccination, with a peak of body temperature of 37.9° ± 0.5°. Patients with fever were younger (39 ± 13 vs. 48 ± 13 years, p = .04). No additional differences in terms of sex and cardiovascular risk factors were found between patients with fever and not. Twenty-seven (84%) out of 32 patients experienced mild fever and five (16%) moderate fever. Pharmacological treatment with antipyretic drugs was required in 18 (56%) out of 32 patients and was associated with the resolution of symptoms. No patient required hospital admission and no arrhythmic episode was recorded in patients with ICD within 48 h after vaccination. No induced type 1 BrS ECG pattern and new ECG features were found among patients with moderate fever.

Conclusion: Fever is a common side effect in BrS patients after the Covid-19 vaccination. Careful evaluation of body temperature and prompt treatment with antipyretic drugs may be needed.
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http://dx.doi.org/10.1111/jce.15596DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9350146PMC
June 2022

Validity of clinical psoriatic arthritis diagnoses made by rheumatologists in the Swedish National Patient Register.

Authors:
J K Wallman G-M Alenius E Klingberg V Sigurdardottir S Wedrén S Exarchou U Lindström D Di Giuseppe J Askling Lth Jacobsson

Scand J Rheumatol 2022 Jun 6:1-11. Epub 2022 Jun 6.

Department of Rheumatology and Inflammation Research, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

Objectives: : Knowledge of the correspondence between clinical ICD diagnoses and classification criteria fulfilment is crucial to interpret studies identifying cases via ICD codes. We assessed the degree to which patients registered with ICD-10 diagnoses of psoriatic arthritis (PsA) in the Swedish National Patient Register (NPR) fulfil established PsA classification criteria.

Method: Four hundred patients with at least one outpatient visit to one of five rheumatology or internal medicine departments (three university/two county departments across Sweden) in 2013-2015, with a main ICD-10 diagnosis of PsA (L40.5, M07.0-M07.3), were randomly selected (80 cases/site). Through a structured medical record review, positive predictive values (PPVs) for fulfilment of the following classification criteria were assessed: CASPAR, Moll and Wright, Vasey and Espinoza, and modified ESSG criteria for PsA. A subset analysis regarding CASPAR fulfilment was also performed among cases with available rheumatoid factor and peripheral X-ray status (central CASPAR items; n = 227).

Results: Of the 400 patients with a main ICD-10 diagnosis of PsA, 343 (86%) fulfilled at least one of the four PsA classification criteria. PPVs for the different criteria were: CASPAR 69% (82% in the subset analysis), Moll and Wright 51%, Vasey and Espinoza 76%, and modified ESSG 64%. Overall, only 6.5% of the 400 PsA diagnoses were judged as clearly incorrect by the medical record reviewers.

Conclusion: The validity of rheumatologist-made, clinical ICD-10 diagnoses for PsA in the Swedish NPR is good, with PPVs of 69-82% for CASPAR fulfilment and 86% for meeting any established PsA classification criteria.
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http://dx.doi.org/10.1080/03009742.2022.2066807DOI Listing
June 2022

Machine learning phenomics (MLP) combining deep learning with time-lapse-microscopy for monitoring colorectal adenocarcinoma cells gene expression and drug-response.

Authors:
M D'Orazio M Murdocca A Mencattini P Casti J Filippi G Antonelli D Di Giuseppe M C Comes C Di Natale F Sangiuolo E Martinelli

Sci Rep 2022 05 20;12(1):8545. Epub 2022 May 20.

Department of Electronic Engineering, University of Rome Tor Vergata, via del Politecnico 1, 00133, Rome, Italy.

High-throughput phenotyping is becoming increasingly available thanks to analytical and bioinformatics approaches that enable the use of very high-dimensional data and to the availability of dynamic models that link phenomena across levels: from genes to cells, from cells to organs, and through the whole organism. The combination of phenomics, deep learning, and machine learning represents a strong potential for the phenotypical investigation, leading the way to a more embracing approach, called machine learning phenomics (MLP). In particular, in this work we present a novel MLP platform for phenomics investigation of cancer-cells response to therapy, exploiting and combining the potential of time-lapse microscopy for cell behavior data acquisition and robust deep learning software architectures for the latent phenotypes extraction. A two-step proof of concepts is designed. First, we demonstrate a strict correlation among gene expression and cell phenotype with the aim to identify new biomarkers and targets for tailored therapy in human colorectal cancer onset and progression. Experiments were conducted on human colorectal adenocarcinoma cells (DLD-1) and their profile was compared with an isogenic line in which the expression of LOX-1 transcript was knocked down. In addition, we also evaluate the phenotypic impact of the administration of different doses of an antineoplastic drug over DLD-1 cells. Under the omics paradigm, proteomics results are used to confirm the findings of the experiments.
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http://dx.doi.org/10.1038/s41598-022-12364-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9123013PMC
May 2022

Correction to: Do patient-reported measures of disease activity in rheumatoid arthritis vary between countries? Results from a Nordic collaboration.

Authors:
Bénédicte Delcoigne Sella Aarrestad Provan Hilde Berner Hammer Daniela Di Giuseppe Thomas Frisell Bente Glintborg Gerdur Grondal Bjorn Gudbjornsson Merete Lund Hetland Brigitte Michelsen Dan Nordström Heikki Relas Johan Askling

Rheumatology (Oxford) 2022 Mar 25. Epub 2022 Mar 25.

Department of Medicine Solna, Clinical Epidemiology Division, Karolinska Institutet, Stockholm, Sweden.

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http://dx.doi.org/10.1093/rheumatology/keac151DOI Listing
March 2022

The impact of a csDMARD in combination with a TNF inhibitor on drug retention and clinical remission in axial spondylarthritis.

Authors:
Michael Nissen Bénédicte Delcoigne Daniela Di Giuseppe Lennart Jacobsson Merete Lund Hetland Adrian Ciurea Lucie Nekvindova Florenzo Iannone Nurullah Akkoc Tuulikki Sokka-Isler Karen Minde Fagerli Maria Jose Santos Catalin Codreanu Manuel Pombo-Suarez Ziga Rotar Bjorn Gudbjornsson Irene van der Horst-Bruinsma Anne Gitte Loft Burkhard Möller Herman Mann Fabrizio Conti Gozde Yildirim Cetin Heikki Relas Brigitte Michelsen Pedro Avila Ribeiro Ruxandra Ionescu Carlos Sanchez-Piedra Matija Tomsic Árni Jón Geirsson Johan Askling

Rheumatology (Oxford) 2022 Mar 22. Epub 2022 Mar 22.

Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Sweden, Stockholm.

Objectives: Many axial spondylarthritis (axSpA) patients receive a conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) in combination with a tumour necrosis factor inhibitor (TNFi). However, the value of this co-therapy remains unclear. The objectives were to describe the characteristics of axSpA patients initiating a first TNFi as monotherapy compared with co-therapy with csDMARD, to compare one-year TNFi retention and remission rates, and to explore the impact of peripheral arthritis.

Methods: Data was collected from 13 European registries. One-year outcomes included TNFi retention and hazard ratios (HR) for discontinuation with 95% confidence intervals (95%CI). Logistic regression was performed with adjusted odds ratios (OR) of achieving remission (ASDAS-CRP < 1.3 and/or BASDAI < 2) and stratified by treatment. Inter-registry heterogeneity was assessed using random-effect meta-analyses, combined results were presented when heterogeneity was not significant. Peripheral arthritis was defined as ≥ 1 swollen joint at baseline (=TNFi start).

Results: Amongst 24 171 axSpA patients, 32% received csDMARD co-therapy (range across countries: 13.5% to 71.2%). The co-therapy group had more baseline peripheral arthritis and higher C-reactive-protein than the monotherapy group. One-year TNFi-retention rates (95%CI): 79% (78-79%) for TNFi monotherapy versus 82% (81-83%) with co-therapy (p< 0.001). Remission was obtained in 20% on monotherapy and 22% on co-therapy (p< 0.001); adjusted OR of 1.16 (1.07-1.25). Remission rates at 12 months were similar in patients with/without peripheral arthritis.

Conclusion: This large European study of axial SpA patients showed similar one-year treatment outcomes for TNFi monotherapy and csDMARD co-therapy, although considerable heterogeneity across countries limited the identification of certain subgroups (e.g. peripheral arthritis) that may benefit from co-therapy.
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http://dx.doi.org/10.1093/rheumatology/keac174DOI Listing
March 2022

The Acute Toxicity of Mineral Fibres: A Systematic In Vitro Study Using Different THP-1 Macrophage Phenotypes.

Authors:
Serena Mirata Vanessa Almonti Dario Di Giuseppe Laura Fornasini Simona Raneri Stefania Vernazza Danilo Bersani Alessandro F Gualtieri Anna Maria Bassi Sonia Scarfì

Int J Mol Sci 2022 Mar 4;23(5). Epub 2022 Mar 4.

Department Earth, Environment and Life Sciences, University of Genova, 16132 Genova, Italy.

Alveolar macrophages are the first line of defence against detrimental inhaled stimuli. To date, no comparative data have been obtained on the inflammatory response induced by different carcinogenic mineral fibres in the three main macrophage phenotypes: M0 (non-activated), M1 (pro-inflammatory) and M2 (alternatively activated). To gain new insights into the different toxicity mechanisms of carcinogenic mineral fibres, the acute effects of fibrous erionite, crocidolite and chrysotile in the three phenotypes obtained by THP-1 monocyte differentiation were investigated. The three mineral fibres apparently act by different toxicity mechanisms. Crocidolite seems to exert its toxic effects mostly as a result of its biodurability, ROS and cytokine production and DNA damage. Chrysotile, due to its low biodurability, displays toxic effects related to the release of toxic metals and the production of ROS and cytokines. Other mechanisms are involved in explaining the toxicity of biodurable fibrous erionite, which induces lower ROS and toxic metal release but exhibits a cation-exchange capacity able to alter the intracellular homeostasis of important cations. Concerning the differences among the three macrophage phenotypes, similar behaviour in the production of pro-inflammatory mediators was observed. The M2 phenotype, although known as a cell type recruited to mitigate the inflammatory state, in the case of asbestos fibres and erionite, serves to support the process by supplying pro-inflammatory mediators.
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http://dx.doi.org/10.3390/ijms23052840DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8911508PMC
March 2022

Do patient-reported measures of disease activity in rheumatoid arthritis vary between countries? Results from a Nordic collaboration.

Authors:
Bénédicte Delcoigne Sella Aarrestad Provan Hilde Berner Hammer Daniela Di Giuseppe Thomas Frisell Bente Glintborg Gerdur Grondal Bjorn Gudbjornson Merete Lund Hetland Brigitte Michelsen Dan Nordström Heikki Relas Johan Askling

Rheumatology (Oxford) 2022 Feb 9. Epub 2022 Feb 9.

Department of Medicine Solna, Clinical Epidemiology Division, Karolinska Institutet, Stockholm, Sweden.

Objectives: To investigate whether patient-reported outcomes vary across countries and are influenced by cultural/contextual factors. Specifically, we aimed to assess inter-country differences in tender joint count (TJC), pain and patient's global health assessment (PGA), and their impact on disease activity (DAS28-CRP) in rheumatoid arthritis (RA) patients from five Nordic countries.

Methods: We collected data (baseline, 3- and 12-months) from rheumatology registers in the five countries comprising RA patients starting a first-ever methotrexate or a first-ever tumor necrosis factor inhibitor (TNFi). In order to assess the role of context (=country), we separately modelled TJC, pain and PGA as functions of objective variables (C-reactive protein, swollen joint count, age, sex, calendar period and disease duration) with linear models. Analyses were performed at each time point and for both treatments. We further assessed the impact of inter-country differences on DAS28-CRP.

Results: 27 645 RA patients started methotrexate and 19 733 started a TNFi. Crude inter-country differences at methotrexate start amounted to up to 4 points (28 points scale) for TJC, 10 and 27 points (0-100 scale) for pain and PGA, respectively. Corresponding numbers at TNFi start were 3 (TJC), 27 (pain) and 24 (PGA) points. All differences were reduced at 3- and 12-months, and attenuated when adjusting for the objective variables. The variation in predicted DAS28-CRP across countries amounted to < 0.5 units.

Conclusions: Inter-country differences in TJC, pain and PGA are greater than expected based on differences in objective measures, but have a small clinical impact on DAS28-CRP across countries.
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http://dx.doi.org/10.1093/rheumatology/keac081DOI Listing
February 2022

Letter to the Editor: Comments on the paper of Wylie and Korchevskiy - Carcinogenicity of fibrous glaucophane: How should we fill the data gaps?

Authors:
Alessandro F Gualtieri Dario Di Giuseppe

Curr Res Toxicol 2022 6;3:100063. Epub 2022 Jan 6.

Department of Chemical and Geological Sciences, The University of Modena and Reggio Emilia, Modena, Italy.

Assessing the human health risk of mineral fibres is an intricate task. In the recent article by Wylie and Korchevskiy (2021) - Carcinogenicity of fibrous glaucophane: how to fill data gaps? (Curr. Res. Toxicol. Vol. 2, pp. 202-203), the authors discuss the potential toxicity and pathogenicity of fibrous glaucophane from the Franciscan Complex, California (USA). Because most of the points of discussion concerns the mineral fibre toxicity/pathogenicity model developed by our research group and the application to the case of fibrous glaucophane (Gualtieri, 2021, Curr. Res. Toxicol. Vol. 2, pp. 42-52), the aim of this Letter is to clear some basic issues, to fill some information gaps and, with a constructive spirit, to provide a complete picture on this topic.
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http://dx.doi.org/10.1016/j.crtox.2021.100063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8762068PMC
January 2022

Al-Substituted Tobermorites: An Effective Cation Exchanger Synthesized from "End-of-Waste" Materials.

Authors:
Daniele Malferrari Fabrizio Bernini Dario Di Giuseppe Valentina Scognamiglio Alessandro F Gualtieri

ACS Omega 2022 Jan 4;7(2):1694-1702. Epub 2022 Jan 4.

Department of Chemical and Geological Sciences, The University of Modena and Reggio Emilia, Via G. Campi 103, Modena I-41125, Italy.

The policies to meet the "zero waste" regime and transition to sustainable circular economy can no longer ignore the use of wastes in place of natural resources, and these daunting and vital societal challenges are nowadays being faced by several nations. The main objective of this work was to search waste materials suitable for a quick and environmentally friendly production of a nanoporous geomaterial able to trap toxic metals at the solid/liquid interface. More specifically, the end-of-waste from the thermal inertization of cement-asbestos and glass powder from domestic glass containers have been employed as sources for the hydrothermal synthesis of a tobermorite-rich material (TRM) successfully tested for the selective removal of Pb, Zn, Cd, and Ni from aqueous solutions. The synthesis was carried out in alkaline solution under mild hydrothermal conditions (120 °C) within 24 h. The quantitative phase analyses of the TRM carried out by applying the Rietveld method showed the occurrence of a large amount of well-crystallized 11 Å Al-substituted tobermorites and an amorphous phase and a lower content of aragonite and calcite. Chemical analyses and thermogravimetric measurements coupled with simultaneous evolved gas mass spectrometry highlighted that Al for Si substitutions in the wollastonite-like tetrahedral chains of tobermorites are balanced by the occurrence of Ca, Na, and K cations in the interlayer rather than by (OH) for O substitutions in the CaO polyhedra. Time-dependent removal tests clearly indicated that metal cations are selectively adsorbed depending on their concentration in solution. Moreover, the kinetic curves showed that the removal of metals from solution is fast and the equilibrium is almost reached in the first 8 h.
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http://dx.doi.org/10.1021/acsomega.1c04193DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8772311PMC
January 2022

A Lab-on-a-Chip Based Automatic Platform for Continuous Nitrites Sensing in Aquaculture.

Authors:
Alexandro Catini Rosamaria Capuano Giuseppe Tancredi Giulio Dionisi Davide Di Giuseppe Joanna Filippi Eugenio Martinelli Corrado Di Natale

Sensors (Basel) 2022 Jan 7;22(2). Epub 2022 Jan 7.

Department of Electronic Engineering, University of Rome Tor Vergata, Via del Politecnico 1, 00133 Rome, Italy.

In aquaculture, the density of fish stock, use of feeding, and surrounding environmental conditions can easily result in an excessive concentration of harmful compounds that require continuous monitoring. Chemical sensors are available for most of these compounds, however, operative conditions and continuous monitoring in water make the development of sensors suitable for long and unattended deployments difficult. A possible solution is the development of engineered automatic labs where the uptake of sample and the contact with water is reduced and the use of a minimal quantity of reagents enables the implementation of reliable chemical assays. In this paper, a platform for automatic chemical assays is presented. The concept is demonstrated with the detection of nitrites based on the well-known colorimetric Griess reaction. The platform is centered around a lab-on-a-chip where reagents and water samples are mixed. The color of the reaction product is measured with low-cost optoelectronic components. Results show the feasibility of the approach with a minimum detectable concentration of about 0.1 mg/L which is below the tolerance level for aquaculture farms.
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http://dx.doi.org/10.3390/s22020444DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8778806PMC
January 2022

Acute cytotoxicity of mineral fibres observed by time-lapse video microscopy.

Authors:
Dario Di Giuseppe Sonia Scarfì Andrea Alessandrini Anna Maria Bassi Serena Mirata Vanessa Almonti Gregorio Ragazzini Andrea Mescola Monica Filaferro Rossella Avallone Giovanni Vitale Valentina Scognamiglio Alessandro F Gualtieri

Toxicology 2022 01 22;466:153081. Epub 2021 Dec 22.

Department of Chemical and Geological Sciences, University of Modena and Reggio Emilia, Modena, Italy.

Inhalation of mineral fibres is associated with the onset of an inflammatory activity in the lungs and the pleura responsible for the development of fatal malignancies. It is known that cell damage is a necessary step for triggering the inflammatory response. However, the mechanisms by which mineral fibres exert cytotoxic activity are not fully understood. In this work, the kinetics of the early cytotoxicity mechanisms of three mineral fibres (i.e., chrysotile, crocidolite and fibrous erionite) classified as carcinogenic by the International Agency for Research on Cancer, was determined for the first time in a comparative manner using time-lapse video microscopy coupled with in vitro assays. All tests were performed using the THP-1 cell line, differentiated into M0 macrophages (M0-THP-1) and exposed for short times (8 h) to 25 μg/mL aliquots of chrysotile, crocidolite and fibrous erionite. The toxic action of fibrous erionite on M0-THP-1 cells is manifested since the early steps (2 h) of the experiment while the cytotoxicity of crocidolite and chrysotile gradually increases during the time span of the experiment. Chrysotile and crocidolite prompt cell death mainly via apoptosis, while erionite exposure is also probably associated to a necrotic-like effect. The potential mechanisms underlying these different toxicity behaviours are discussed in the light of the different morphological, and chemical-physical properties of the three fibres.
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http://dx.doi.org/10.1016/j.tox.2021.153081DOI Listing
January 2022

European bio-naïve spondyloarthritis patients initiating TNFi: Time trends in baseline characteristics, treatment retention and response.

Authors:
Sara Nysom Christiansen Lykke Midtbøll Ørnbjerg Simon Horskjær Rasmussen Anne Gitte Loft Johan Askling Florenzo Iannone Jakub Zavada Brigitte Michelsen Michael Nissen Fatos Onen Maria Jose Santos Manuel Pombo-Suarez Heikki Relas Gary J Macfarlane Matija Tomsic Catalin Codreanu Bjorn Gudbjornsson Irene Van der Horst-Bruinsma Daniela Di Giuseppe Bente Glintborg Elisa Gremese Karel Pavelka Eirik Klami Kristianslund Adrian Ciurea Nurullah Akkoc Anabela Barcelos Carlos Sánchez-Piedra Ritva Peltomaa Gareth T Jones Ziga Rotar

Rheumatology (Oxford) 2021 Dec 23. Epub 2021 Dec 23.

University Medical Centre Ljubljana, Department of Rheumatology, and University of Ljubljana, Faculty of Medicine, Ljubljana, Slovenia.

Objectives: To investigate time trends in baseline characteristics and retention, remission and response rates in bio-naïve axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) patients initiating tumour necrosis factor inhibitor (TNFi) treatment.

Methods: Prospectively collected data on bio-naïve axSpA and PsA patients from routine care in 15 European countries were pooled. Three cohorts were defined according to year of TNFi-initiation: A (1999-2008), B (2009-2014) and C (2015-2018). Retention, remission and response rates were assessed at 6, 12 and 24 months.

Results: In total, 27 149 axSpA and 17 446 PsA patients were included.Cohort A patients had longer disease duration compared with B and C. In axSpA, cohort A had the largest proportion of male and HLA-B27 positive patients. In PsA, baseline disease activity was highest in cohort A.Retention rates in axSpA/PsA were highest in cohort A and differed only slightly between B and C.For all cohorts, disease activity decreased markedly from 0 to 6 months. In axSpA, disease activity at 24 months was highest in cohort A, where also remission and response rates were lowest. In PsA, remission rates at 6 and 12 months tended to be lowest in cohort A. Response rates were at all time points comparable across cohorts, and less between-cohort disease activity differences were seen at 24 months.

Conclusion: Our findings indicate that over the past decades, clinicians have implemented more aggressive treatment strategies in spondyloarthritis. This was illustrated by shorter disease duration at treatment initiation, decreased retention rates and higher remission rates during recent years.
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http://dx.doi.org/10.1093/rheumatology/keab945DOI Listing
December 2021

The occurrence of multiple treatment switches in axial spondyloarthritis. Results from five Nordic rheumatology registries.

Authors:
Daniela Di Giuseppe Ulf Lindström Kalle Aaltonen Heikki Relas Sella Provan Bjorn Gudbjornsson Merete Lund Hetland Johan Askling Markku Kauppi Arni Jon Geirsson Katerina Chatzidionysiou Tanja Schjødt Jørgensen Lene Dreyer Brigitte Michelsen Lennart Jacobsson Bente Glintborg

Rheumatology (Oxford) 2021 Dec 23. Epub 2021 Dec 23.

DANBIO and Copenhagen Center for Arthritis Research (COPECARE), Center for Rheumatology and Spine Diseases, Centre of Head and Orthopedics, Copenhagen University Hospital, Rigshospitalet, Glostrup, Copenhagen, Denmark.

Objectives: In axial spondyloarthritis (axSpA), switching between multiple biologic or targeted synthetic (b/ts-) DMARDs might indicate difficult-to-treat disease. We aimed to explore the occurrence of multiple switching in routine care axSpA patients using various definitions, and to identify associated clinical characteristics upon start of first b/tsDMARD (baseline).

Methods: Observational cohort study including patients with axSpA starting a first-ever b/tsDMARD 2009-2018 based on data from five biologic registries (Denmark/Sweden/Finland/Norway/Iceland). Comorbidities and extra-articular manifestations were identified through linkage to national registries. Multi-switching was defined in overlapping categories according to b/tsDMARD treatment history: treatment with ≥3 b/tsDMARDs, ≥4 or ≥ 5 b/tsDMARDs during follow-up. We explored the cumulative incidence of patients becoming multi-switchers with ≥3 b/tsDMARDs stratified by calendar-period (2009-11/2012-13/2014-15/2016-2018). In the subgroup of patients starting a first b/tsDMARD 2009-2015, baseline characteristics associated with multi-switching (within 3 years' follow-up) were explored using multiple logistic regression analyses.

Results: Among 8,398 patients included, 6,056 patients (63% male, median age 42 years) started a first b/tsDMARD 2009-2015, whereof proportions treated with ≥3, ≥4 or ≥ 5 b/tsDMARDs within 3 years' follow-up were 8%, 3%, 1%, respectively.Calendar-period did not affect the cumulative incidence of multi-switching.Baseline characteristics associated with multi-switching (≥3 b/tsDMARDs) were female gender, shorter disease duration, higher patient global score, comorbidities, and having psoriasis but not uveitis.

Conclusion: In this large Nordic observational cohort of axSpA patients, multiple switching was frequent with no apparent time-trend. Clinical associated factors included gender, but also previous comorbidities and extraarticular manifestations illustrating the ongoing challenge of treating this patient group.
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http://dx.doi.org/10.1093/rheumatology/keab946DOI Listing
December 2021

Comparison of treatment retention of originator vs biosimilar products in clinical rheumatology practice in Sweden.

Authors:
Daniela Di Giuseppe Ulf Lindstrom Hannah Bower Bénédicte Delcoigne Thomas Frisell Katerina Chatzidionysiou Christopher Sjöwall Elisabet Lindqvist Johan Askling

Rheumatology (Oxford) 2021 Dec 17. Epub 2021 Dec 17.

Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Sweden.

Objectives: To compare treatment retention between biosimilars and their originator products among first starters (etanercept, infliximab, adalimumab and rituximab), as well as after non-medical switch.

Methods: Patients with rheumatic diseases starting, for the first time, an originator or biosimilar etanercept, infliximab, adalimumab, and rituximab were identified in the national Swedish Rheumatology Quality register. Moreover, patients switching from an originator to its biosimilar were identified, and individually matched to patients continuing on the originator. One-year treatment retention was calculated, and hazard ratios (HR) for discontinuation with 95% confidence intervals (CI) were estimated, adjusting for comorbidities and socioeconomic factors.

Results: In total, 21443 first treatment courses were identified. The proportion of patients still on drug at one year, and the HR for discontinuation, revealed no differences across adalimumab (Humira, Imraldi, Amgevita and Hyrimoz) nor across rituximab products (Mabthera, Ritemvia/Truxima and Rixathon). The proportions on drug at one year were similar for Benepali (77%) and Enbrel (75%) and the adjusted HR for Benepali compared to Enbrel was 0.91 (95% CI: 0.83-0.99). For infliximab, the proportion still on drug at one year was 67% for Remicade and 66% for Remsima/Inflectra, and the HR in comparison with Remicade was: 1.16 (95% CI: 1.02-1.33).Among 2925 patients switching from an originator drug to one of its biosimilars, we noted no statistically significant or clinically relevant differences in drug survival compared those who remained on originator therapy.

Conclusion: This large observational study supports the equivalence of bDMARD biosimilar products and originators when used in routine rheumatology care.
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http://dx.doi.org/10.1093/rheumatology/keab933DOI Listing
December 2021

Effects of the COVID-19 pandemic on patients with inflammatory joint diseases in Sweden: from infection severity to impact on care provision.

Authors:
Hannah Bower Thomas Frisell Daniela di Giuseppe Bénédicte Delcoigne Gerd-Marfie Ahlenius Eva Baecklund Katerina Chatzidionysiou Nils Feltelius Helena Forsblad-d'Elia Alf Kastbom Lars Klareskog Elisabet Lindqvist Ulf Lindström Carl Turesson Christopher Sjowall Johan Askling

RMD Open 2021 12;7(3)

Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.

Objectives: To compare risks for COVID-19-related outcomes in inflammatory joint diseases (IJDs) and across disease-modifying antirheumatic drugs (DMARDs) during the first two waves of the pandemic and to assess effects of the pandemic on rheumatology care provision.

Methods: Through nationwide multiregister linkages and cohort study design, we defined IJD and DMARD use annually in 2015-2020. We assessed absolute and relative risks of hospitalisation or death listing COVID-19. We also assessed the incidence of IJD and among individuals with IJD, rheumatologist visits, DMARD use and incidence of selected comorbidities.

Results: Based on 115 317 patients with IJD in 2020, crude risks of hospitalisation and death listing COVID-19 (0.94% and 0.33% across both waves, respectively) were similar during both waves (adjusted HR versus the general population 1.33, 95% CI 1.23 to 1.43, for hospitalisation listing COVID-19; 1.23, 95% CI 1.08 to 1.40 for death listing COVID-19). Overall, biological disease-modifying antirheumatic drugs (bDMARDs)/targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs) did not increase risks of COVID-19 related hospitalisation (with the exception of a potential signal for JAK inhibitors) or death. During the pandemic, decreases were observed for IJD incidence (-7%), visits to rheumatology units (-16%), DMARD dispensations (+6.5% for bDMARD/tsDMARDs and -8.5% for conventional synthetic DMARDs compared with previous years) and for new comorbid conditions, but several of these changes were part of underlying secular trends.

Conclusions: Patients with IJD are at increased risk of serious COVID-19 outcomes, which may partially be explained by medical conditions other than IJD per se. The SARS-CoV-2 pandemic has exerted measurable effects on aspects of rheumatology care provision demonstrated, the future impact of which will need to be assessed.
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http://dx.doi.org/10.1136/rmdopen-2021-001987DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8655349PMC
December 2021

Characterisation of potentially toxic natural fibrous zeolites by means of electron paramagnetic resonance spectroscopy and morphological-mineralogical studies.

Authors:
Matteo Giordani Michele Mattioli Michela Cangiotti Alberto Fattori Maria Francesca Ottaviani Michele Betti Paolo Ballirano Alessandro Pacella Dario Di Giuseppe Valentina Scognamiglio Miriam Hanuskova Alessandro F Gualtieri

Chemosphere 2022 Mar 24;291(Pt 3):133067. Epub 2021 Nov 24.

Department of Chemical and Geological Sciences, University of Modena and Reggio Emilia, I-41125, Modena, Italy.

This study explored the morphological, mineralogical, and physico-chemical features of carcinogenic erionite and other possibly hazardous zeolites, such as mesolite and thomsonite, while also investigating the interacting capability of the mineral surface at the liquid/solid interface. Extremely fibrous erionite is K and Ca-rich and shows the highest Si/Al ratio (3.38) and specific surface area (8.14 m/g). Fibrous mesolite is Na and Ca-rich and displays both a lower Si/Al ratio (1.56) and a smaller specific surface area (1.56 m/g). The thomsonite composition shows the lowest values of Si/Al ratio (1.23) and specific surface area (0.38 m/g). Electron paramagnetic resonance data from selected spin probes reveal that erionite has a homogeneous site distribution and interacts well with all spin probes. The surfaces of mesolite and thomsonite are less homogeneous and closer polar sites were found through consequent interaction with the probes. The mesolite surface can also clearly interact but with a lower strength and may represent a potential health hazard for humans, though with a lower degree if compared to erionite. The thomsonite surface is not inert and interacts with the probes with a low-grade capability. We can expect small fragments of thomsonite to interact with the biological environment, though with a low-grade intensity.
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http://dx.doi.org/10.1016/j.chemosphere.2021.133067DOI Listing
March 2022

Influenza outcomes in patients with inflammatory joint diseases and DMARDs: how do they compare to those of COVID-19?

Authors:
Hannah Bower Thomas Frisell Daniela Di Giuseppe Bénédicte Delcoigne Johan Askling

Ann Rheum Dis 2022 03 22;81(3):433-439. Epub 2021 Nov 22.

Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.

Objectives: To estimate absolute and relative risks for seasonal influenza outcomes in patients with inflammatory joint diseases (IJDs) and disease-modifying antirheumatic drugs (DMARDs). To contextualise recent findings on corresponding COVID-19 risks.

Methods: Using Swedish nationwide registers for this cohort study, we followed 116 989 patients with IJD and matched population comparators across four influenza seasons (2015-2019). We quantified absolute risks of hospitalisation and death due to influenza, and compared IJD to comparators via Cox regression. We identified 71 556 patients with IJD on active treatment with conventional synthetic DMARDs and biological disease-modifying antirheumatic drugs (bDMARDs)/targeted synthetic disease-modifying antirheumatic drug (tsDMARDs) at the start of each influenza season, estimated risks for the same outcomes and compared these risks across DMARDs via Cox regression.

Results: Per season, average risks for hospitalisation listing influenza were 0.25% in IJD and 0.1% in the general population, corresponding to a crude HR of 2.38 (95% CI 2.21 to 2.56) that decreased to 1.44 (95% CI 1.33 to 1.56) following adjustments for comorbidities. For death listing influenza, the corresponding numbers were 0.015% and 0.006% (HR=2.63, 95% CI 1.93 to 3.58, and HR=1.46, 95% CI 1.07 to 2.01). Absolute risks for influenza outcomes were half (hospitalisation) and one-tenth (death) of those for COVID-19, but relative estimates comparing IJD to the general population were similar.

Conclusions: In absolute terms, COVID-19 in IJD outnumbers that of average seasonal influenza, but IJD entails a 50%-100% increase in risk for hospitalisation and death for both types of infections, which is largely dependent on associated comorbidities. Overall, bDMARDs/tsDMARDs do not seem to confer additional risk for hospitalisation or death related to seasonal influenza.
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http://dx.doi.org/10.1136/annrheumdis-2021-221461DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8610614PMC
March 2022

Risk of acute myocardial infarction in sarcoidosis: A population-based cohort study from Sweden.

Authors:
Marios Rossides Susanna Kullberg Johan Grunewald Anders Eklund Daniela Di Giuseppe Johan Askling Elizabeth V Arkema

Respir Med 2021 11 22;188:106624. Epub 2021 Sep 22.

Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.

Due to conflicting findings in previous studies, it remains unclear whether individuals with sarcoidosis are at a higher relative risk of acute myocardial infarction. In this cohort study, individuals with sarcoidosis and matched general population comparators were followed for acute myocardial infarction in Swedish nationwide registers. A small (20%) risk increase associated with sarcoidosis was identified, which did not markedly vary by age at diagnosis, sex, treatment status around diagnosis, and time since diagnosis. The highest relative risk (1.4) was observed in individuals who received immunosuppressant treatment around the time of sarcoidosis diagnosis. Future studies should examine the clinical characteristics of acute myocardial infarction in these patients and investigate whether early diagnostic or preventive interventions might be beneficial for these patients.
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http://dx.doi.org/10.1016/j.rmed.2021.106624DOI Listing
November 2021

Is tea consumption associated with reduction of risk of rheumatoid arthritis? A Swedish case-control study.

Authors:
Helga Westerlind Ida Palmqvist Saedis Saevarsdottir Lars Alfredsson Lars Klareskog Daniela Di Giuseppe

Arthritis Res Ther 2021 08 7;23(1):209. Epub 2021 Aug 7.

Clinical Epidemiology Division, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.

Background: Tea is a popular beverage around the world and has properties that can affect the immune system. The association between tea consumption and the risk of rheumatoid arthritis (RA), a chronic autoimmune disease primarily affecting the joints, is not well studied and results are conflicting.

Methods: We collected data on tea consumption for 2237 incident RA cases diagnosed 2005-2018 and 4661 controls matched on age, sex, and residential area. Tea consumption was classified into no (0 cups/day), irregular (< 1 cup/day), regular (1-2 cups/day), and high (≥ 2 cups/day) consumption, and irregular consumption was used as the reference category. Missing data on tea consumption was classified as no consumers, and sensitivity analyses were performed to test this assumption. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression, adjusting for smoking, coffee, alcohol, educational level, and body mass index. We also performed stratified analysis on sex, anti-citrullinated autoantibody (ACPA) status, and smoking habits.

Results: Among the cases, we found 57.3% to be ever consumers of tea with 19.7 having a high tea consumption. Corresponding figures for the controls were 58.4% ever drinkers with 22.1% high tea consumers. High tea consumption had an inverse association to the risk of RA compared to irregular consumption [OR = 0.78 (95% CI 0.66-0.92)], but the association lost statistical significance in the adjusted model [adjusted OR (adjOR) = 0.85 (95% CI 0.71-1.01)]. Among non-tea consumers, a protective effect was also observed compared to irregular consumers [adjOR = 0.82 (95% CI 0.70-0.88)], but this association did not withstand sensitivity analysis, possibly due to bias. In the ACPA-positive group and among current smokers, a protective effect of tea consumption was observed among the high tea consumers [adjOR = 0.76 (95% CI 0.62-0.94) and adjOR = 0.60 (95% CI 0.38-0.95), respectively].

Conclusions: This study suggests a protective effect of high consumption of tea, among smokers and for ACPA-positive RA.

Trial Registration: Not applicable.
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http://dx.doi.org/10.1186/s13075-021-02583-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8349003PMC
August 2021

Combining microfluidics with machine learning algorithms for RBC classification in rare hereditary hemolytic anemia.

Authors:
Valeria Rizzuto Arianna Mencattini Begoña Álvarez-González Davide Di Giuseppe Eugenio Martinelli David Beneitez-Pastor Maria Del Mar Mañú-Pereira Maria José Lopez-Martinez Josep Samitier

Sci Rep 2021 06 30;11(1):13553. Epub 2021 Jun 30.

Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology BIST, 08028, Barcelona, Spain.

Combining microfluidics technology with machine learning represents an innovative approach to conduct massive quantitative cell behavior study and implement smart decision-making systems in support of clinical diagnostics. The spleen plays a key-role in rare hereditary hemolytic anemia (RHHA), being the organ responsible for the premature removal of defective red blood cells (RBCs). The goal is to adapt the physiological spleen filtering strategy for in vitro study and monitoring of blood diseases through RBCs shape analysis. Then, a microfluidic device mimicking the slits of the spleen red pulp area and video data analysis are combined for the characterization of RBCs in RHHA. This microfluidic unit is designed to evaluate RBC deformability by maintaining them fixed in planar orientation, allowing the visual inspection of RBC's capacity to restore their original shape after crossing microconstrictions. Then, two cooperative learning approaches are used for the analysis: the majority voting scheme, in which the most voted label for all the cell images is the class assigned to the entire video; and the maximum sum of scores to decide the maximally scored class to assign. The proposed platform shows the capability to discriminate healthy controls and patients with an average efficiency of 91%, but also to distinguish between RHHA subtypes, with an efficiency of 82%.
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http://dx.doi.org/10.1038/s41598-021-92747-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245545PMC
June 2021

NeuriTES. Monitoring neurite changes through transfer entropy and semantic segmentation in bright-field time-lapse microscopy.

Authors:
Arianna Mencattini Alida Spalloni Paola Casti Maria Colomba Comes Davide Di Giuseppe Gianni Antonelli Michele D'Orazio Joanna Filippi Francesca Corsi Hervé Isambert Corrado Di Natale Patrizia Longone Eugenio Martinelli

Patterns (N Y) 2021 Jun 25;2(6):100261. Epub 2021 May 25.

Department of Electronic Engineering, University of Rome Tor Vergata, 00133 Rome, Italy.

One of the most challenging frontiers in biological systems understanding is fluorescent label-free imaging. We present here the NeuriTES platform that revisits the standard paradigms of video analysis to detect unlabeled objects and adapt to the dynamic evolution of the phenomenon under observation. Object segmentation is reformulated using robust algorithms to assure regular cell detection and transfer entropy measures are used to study the inter-relationship among the parameters related to the evolving system. We applied the NeuriTES platform to the automatic analysis of neurites degeneration in presence of amyotrophic lateral sclerosis (ALS) and to the study of the effects of a chemotherapy drug on living prostate cancer cells (PC3) cultures. Control cells have been considered in both the two cases study. Accuracy values of 93% and of 92% are achieved, respectively. NeuriTES not only represents a tool for investigation in fluorescent label-free images but demonstrates to be adaptable to individual needs.
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http://dx.doi.org/10.1016/j.patter.2021.100261DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8212146PMC
June 2021

Anterior uveitis in patients with spondyloarthritis treated with secukinumab or tumour necrosis factor inhibitors in routine care: does the choice of biological therapy matter?

Authors:
Ulf Lindström Karin Bengtsson Tor Olofsson Daniela Di Giuseppe Bente Glintborg Helena Forsblad-d'Elia Lennart T H Jacobsson Johan Askling

Ann Rheum Dis 2021 11 15;80(11):1445-1452. Epub 2021 Jun 15.

Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.

Background: The effect of interleukin 17-inhibitors on anterior uveitis (AU) in spondyloarthritis (SpA) is poorly understood. This study aimed to compare the risk of AU during treatment with secukinumab versus tumour necrosis factor inhibitors (TNFi).

Methods: Patients with SpA starting secukinumab or a TNFi 2015 through 2018 were identified in the Swedish Rheumatology Quality Register. Occurrence of AU was identified based on diagnosis codes in outpatient ophthalmology care in the National Patient Register. The main outcomes were crude rates of AU-diagnoses per 100 patient-years, and adjusted HRs for AU, during treatment, in patients without AU during the year before treatment start (in order to reduce confounding by indication). HRs were adjusted for age, sex, history of AU and patient global assessment of disease activity.

Results: Based on 4851 treatment starts (456 secukinumab; 4395 any TNFi), the rate of AU-diagnoses per 100 patient-years was 6.8 (95% CI 5.2 to 8.7) for secukinumab. Among the TNFi, the rate varied from 2.9 (95% CI 2.1 to 3.7) for infliximab and 4.0 (95% CI 3.3 to 4.9) for adalimumab to 7.5 (95% CI 6.7 to 8.4) for etanercept. The adjusted HRs for first AU (adalimumab as reference) were: secukinumab 2.32 (95% CI 1.16 to 4.63), infliximab 0.99 (95% CI 0.49 to 1.96), etanercept 1.82 (95% CI 1.13 to 2.93), golimumab 1.59 (95% CI 0.90 to 2.80) and certolizumab 1.12 (95% CI 0.44 to 2.83). Sensitivity analyses confirmed the pattern of higher AU rates with secukinumab and etanercept versus monoclonal TNFi.

Conclusion: As used in clinical practice in SpA, secukinumab appears to be associated with a higher risk of AU, compared with the monoclonal TNFi and a similar risk compared with etanercept.
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http://dx.doi.org/10.1136/annrheumdis-2021-220420DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8522450PMC
November 2021

Effectiveness and treatment retention of TNF inhibitors when used as monotherapy versus comedication with csDMARDs in 15 332 patients with psoriatic arthritis. Data from the EuroSpA collaboration.

Authors:
Ulf Lindström Daniela Di Giuseppe Bénédicte Delcoigne Bente Glintborg Burkhard Möller Adrian Ciurea Manuel Pombo-Suarez Carlos Sanchez-Piedra Kari Eklund Heikki Relas Bjorn Gudbjornsson Thorvardur Jon Love Gareth T Jones Catalin Codreanu Ruxandra Ionescu Lucie Nekvindova Jakub Závada Nuh Atas Servet Yolbas Karen Minde Fagerli Brigitte Michelsen Žiga Rotar Matija Tomšič Florenzo Iannone Maria Jose Santos Pedro Avila-Ribeiro Lykke Midtbøll Ørnbjerg Mikkel Østergaard Lennart Th Jacobsson Johan Askling

Ann Rheum Dis 2021 11 3;80(11):1410-1418. Epub 2021 Jun 3.

Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.

Background: Comedication with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) during treatment with tumour necrosis factor inhibitors (TNFi) is extensively used in psoriatic arthritis (PsA), although the additive benefit remains unclear. We aimed to compare treatment outcomes in patients with PsA treated with TNFi and csDMARD comedication versus TNFi monotherapy.

Methods: Patients with PsA from 13 European countries who initiated a first TNFi in 2006-2017 were included. Country-specific comparisons of 1 year TNFi retention were performed by csDMARD comedication status, together with HRs for TNFi discontinuation (comedication vs monotherapy), adjusted for age, sex, calendar year, disease duration and Disease Activity Score with 28 joints (DAS28). Adjusted ORs of clinical remission (based on DAS28) at 12 months were calculated. Between-country heterogeneity was assessed using random-effect meta-analyses, combined results were presented when heterogeneity was not significant. Secondary analyses stratified according to TNFi subtype (adalimumab/infliximab/etanercept) and restricted to methotrexate as comedication were performed.

Results: In total, 15 332 patients were included (62% comedication, 38% monotherapy). TNFi retention varied across countries, with significant heterogeneity precluding a combined estimate. Comedication was associated with better remission rates, pooled OR 1.25 (1.12-1.41). Methotrexate comedication was associated with improved remission for adalimumab (OR 1.45 (1.23-1.72)) and infliximab (OR 1.55 (1.21-1.98)) and improved retention for infliximab. No effect of comedication was demonstrated for etanercept.

Conclusion: This large observational study suggests that, as used in clinical practice, csDMARD and TNFi comedication are associated with improved remission rates, and specifically, comedication with methotrexate increases remission rates for both adalimumab and infliximab.
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http://dx.doi.org/10.1136/annrheumdis-2021-220097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8522446PMC
November 2021

Risk and predictors of heart failure in sarcoidosis in a population-based cohort study from Sweden.

Authors:
Marios Rossides Susanna Kullberg Johan Grunewald Anders Eklund Daniela Di Giuseppe Johan Askling Elizabeth V Arkema

Heart 2022 03 21;108(6):467-473. Epub 2021 May 21.

Department of Medicine Solna, Clinical Epidemiology Division, Karolinska Institutet, Stockholm, Sweden.

Objectives: Previous studies showed a strong association between sarcoidosis and heart failure (HF) but did not consider risk stratification or risk factors to identify useful aetiological insights. We estimated overall and stratified HRs and identified risk factors for HF in sarcoidosis.

Methods: Sarcoidosis cases were identified from the Swedish National Patient Register (NPR; ≥2 International Classification of Diseases-coded visits, 2003-2013) and matched to general population comparators. They were followed for HF in the NPR. Treated were cases who were dispensed ≥1 immunosuppressant ±3 months from the first sarcoidosis visit (2006-2013). Using Cox models, we estimated HRs adjusted for demographics and comorbidity and identified independent risk factors of HF together with their attributable fractions (AFs).

Results: During follow-up, 204 of 8574 sarcoidosis cases and 721 of 84 192 comparators were diagnosed with HF (rate 2.2 vs 0.7/1000 person-years, respectively). The HR associated with sarcoidosis was 2.43 (95% CI 2.06 to 2.86) and did not vary by age, sex or treatment status. It was higher during the first 2 years after diagnosis (HR 3.7 vs 1.9) and in individuals without a history of ischaemic heart disease (IHD; HR 2.7 vs 1.7). Diabetes, atrial fibrillation and other arrhythmias were the strongest independent clinical predictors of HF (HR 2.5 each, 2-year AF 20%, 16% and 12%, respectively).

Conclusions: Although low, the HF rate was more than twofold increased in sarcoidosis compared with the general population, particularly right after diagnosis. IHD history cannot solely explain these risks, whereas ventricular arrhythmias indicating cardiac sarcoidosis appear to be a strong predictor of HF in sarcoidosis.
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http://dx.doi.org/10.1136/heartjnl-2021-319129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8899480PMC
March 2022

Occurrence and characterization of tremolite asbestos from the Mid Atlantic Ridge.

Authors:
Dario Di Giuseppe Natale Perchiazzi Daniele Brunelli Tommaso Giovanardi Luca Nodari Giancarlo Della Ventura Daniele Malferrari Marcia Maia Alessandro F Gualtieri

Sci Rep 2021 03 18;11(1):6285. Epub 2021 Mar 18.

Department of Chemical and Geological Sciences, University of Modena and Reggio Emilia, Modena, Italy.

Tremolite is one of the most common amphibole species and, in the fibrous form (i.e., characterized by crystals/particles consisting of fibres with length > 5 µm, width < 3 µm and aspect ratio > 3), one of the six asbestos minerals. Until now the attention of crystallographers has focused only on samples from continental environment. Here we report the first chemical and structural data of a tremolite asbestos found along the Mid Atlantic Ridge (MAR) at the eastern intersection of the Romanche Transform Fault (Equatorial MAR). Tremolite is associated with chlorite and lizardite and was formed through the green shale facies lower than zeolite in a predominantly fluid system. MAR tremolite asbestos shows very slight deviations from the ideal crystal structure of tremolite. Differences in cation site partitioning were found with respect to tremolite asbestos from ophiolitic complexes, attributed to the different chemical-physical conditions during the mineral formation. In particular, oceanic tremolite asbestos is enriched in Al and Na, forming a trend clearly distinct from the continental tremolites.
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http://dx.doi.org/10.1038/s41598-021-85576-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7973559PMC
March 2021

In vitro toxicity of fibrous glaucophane.

Authors:
Alessandro F Gualtieri Alessandro Zoboli Monica Filaferro Monia Benassi Sonia Scarfì Serena Mirata Rossella Avallone Giovanni Vitale Mark Bailey Martin Harper Dario Di Giuseppe

Toxicology 2021 04 3;454:152743. Epub 2021 Mar 3.

Department of Chemical and Geological Sciences, University of Modena and Reggio Emilia, Modena, Italy. Electronic address:

The health hazard represented by the exposure to asbestos may also concern other minerals with asbestos-like crystal habit. One of these potentially hazardous minerals is fibrous glaucophane. Fibrous glaucophane is a major component of blueschist rocks of California (USA) currently mined for construction purposes. Dust generated by the excavation activities might potentially expose workers and the general public. The aim of this study was to determine whether fibrous glaucophane induces in vitro toxicity effects on lung cells by assessing the biological responses of cultured human pleural mesothelial cells (Met-5A) and THP-1 derived macrophages exposed for 24 h and 48 h to glaucophane fibres. Crocidolite asbestos was tested for comparison. The experimental configuration of the in vitro tests included a cell culture without fibres (i.e., control), cell cultures treated with 50 μg/mL (i.e., 15.6 μg/cm) of crocidolite fibres and 25-50-100 μg/mL (i.e., 7.8-15.6-31.2 μg/cm) of glaucophane fibres. Results showed that fibrous glaucophane may induce a decrease in cell viability and an increase in extra-cellular lactate dehydrogenase release in the tested cell cultures in a concentration dependent mode. Moreover, it was found that fibrous glaucophane has a potency to cause oxidative stress. The biological reactivity of fibrous glaucophane confirms that it is a toxic agent and, although it apparently induces lower toxic effects compared to crocidolite, exposure to this fibre may be responsible for the development of lung diseases in exposed unprotected workers and population.
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http://dx.doi.org/10.1016/j.tox.2021.152743DOI Listing
April 2021

Rapid Manufacturing of Multilayered Microfluidic Devices for Organ on a Chip Applications.

Authors:
Roberto Paoli Davide Di Giuseppe Maider Badiola-Mateos Eugenio Martinelli Maria Jose Lopez-Martinez Josep Samitier

Sensors (Basel) 2021 Feb 16;21(4). Epub 2021 Feb 16.

Nanobioengineering Group, Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology (BIST), 12 Baldiri Reixac 15-21, 08028 Barcelona, Spain.

Microfabrication and Polydimethylsiloxane (PDMS) soft-lithography techniques became popular for microfluidic prototyping at the lab, but even after protocol optimization, fabrication is yet a long, laborious process and partly user-dependent. Furthermore, the time and money required for the master fabrication process, necessary at any design upgrade, is still elevated. Digital Manufacturing (DM) and Rapid-Prototyping (RP) for microfluidics applications arise as a solution to this and other limitations of photo and soft-lithography fabrication techniques. Particularly for this paper, we will focus on the use of subtractive DM techniques for Organ-on-a-Chip (OoC) applications. Main available thermoplastics for microfluidics are suggested as material choices for device fabrication. The aim of this review is to explore DM and RP technologies for fabrication of an OoC with an embedded membrane after the evaluation of the main limitations of PDMS soft-lithography strategy. Different material options are also reviewed, as well as various bonding strategies. Finally, a new functional OoC device is showed, defining protocols for its fabrication in Cyclic Olefin Polymer (COP) using two different RP technologies. Different cells are seeded in both sides of the membrane as a proof of concept to test the optical and fluidic properties of the device.
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http://dx.doi.org/10.3390/s21041382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920479PMC
February 2021
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