Publications by authors named "Giuseppe D"

84 Publications

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

Sci Rep 2021 Mar 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.

Toxicology 2021 Apr 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.

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

Effectiveness of a second biologic after failure of a non-tumor necrosis factor inhibitor as first biologic in rheumatoid arthritis.

J Rheumatol 2021 Mar 1. Epub 2021 Mar 1.

Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; DANBIO and Copenhagen Center for Arthritis Research (COPECARE), Center for Rheumatology and Spine Diseases, Centre of Head and Orthopedics, Rigshospitalet, Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; On behalf of the DANBIO Registry, Copenhagen Denmark; Helsinki University and Hospital (ROB-FIN), Departments of Medicine and Rheumatology, Helsinki, Finland; Pharmaceuticals Pricing Board, Ministry of Social Affairs and Health, Helsinki, Finland. Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway; Centre for Rheumatology Research, University Hospital, and Faculty of Medicine, University of Iceland, Reykjavik, Iceland; Department of Rheumatology and Centre for Rheumatology Research, University Hospital, Reykjavik, Iceland; Department of Rheumatology, Aalborg University Hospital, Aalborg, Denmark; Department of Clinical Medicine, Aalborg University, Aalborg, Denmark; The Parker Institute, Copenhagen University Hospital, Bispebjerg and Frederiksberg, Copenhagen F, Denmark; Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. Address correspondence to Katerina Chatzidionysiou, MD, PhD. Rheumatology Unit, Karolinska University Hospital, D2:00, 171 76, Solna, Stockholm, Sweden.

Objective: In Rheumatoid Arthritis (RA), evidence regarding the effectiveness of a second biologic Disease Modifying Anti-Rheumatic Drugs (bDMARDs) in patients whose first ever bDMARD was a non-tumor-necrosis-factor-inhibitor (TNFi) bDMARD is limited. The objective of this study was therefore to assess the outcome of the second bDMARD (non-TNFi [rituximab, abatacept or tocilizumab, separately] and TNFi) after failure of a non-TNFi bDMARD as first bDMARD.

Methods: We identified RA patients from the five Nordic biologics registers started treatment with a non-TNFi as first ever bDMARD but switched to a second bDMARD. For the second bDMARD, we assessed survival-on-drug (at 6 and 12 months), and primary response (at 6 months).

Results: We included 620 patients starting a second bDMARD (ABA 86, RTX 40, TCZ 67 and TNFi 427) following failure of a first non-TNFI bDMARD. At 6 and 12 months after start of their second bDMARD, around 70% and 50%, respectively, remained on treatment, and at 6 months less than one third of patients were still on their second bDMARD and had reached low disease activity or remission according to DAS28. For those patients whose second bMDARD was a TNFI, the corresponding proportion was slightly higher (40%).

Conclusion: The survival-on-drug and primary response of a second bDMARD in RA patients switching due to failure of a non-TNFi bDMARD as first bDMARD is modest. Some patients may benefit from TNFi when used after failure of a non-TNFi as first bDMARD.
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http://dx.doi.org/10.3899/jrheum.201467DOI Listing
March 2021

Impact of the COVID-19 pandemic on morbidity and mortality in patients with inflammatory joint diseases and in the general population: a nationwide Swedish cohort study.

Ann Rheum Dis 2021 Feb 23. Epub 2021 Feb 23.

Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.

Objectives: To estimate absolute and relative risks for all-cause mortality and for severe COVID-19 in inflammatory joint diseases (IJDs) and with antirheumatic therapies.

Methods: Through Swedish nationwide multiregister linkages, we selected all adult patients with rheumatoid arthritis (RA, n=53 455 in March 2020), other IJDs (here: spondyloarthropathies, psoriatic arthritis and juvenile idiopathic arthritis, n=57 112), their antirheumatic drug use, and individually matched population referents. We compared annual all-cause mortality March-September 2015 through 2020 within and across cohorts, and assessed absolute and relative risks for hospitalisation, admission to intensive care and death due to COVID-19 March-September 2020, using Cox regression.

Results: During March-September 2020, the absolute all-cause mortality in RA and in other IJDs was higher than 2015-2019, but relative risks versus the general population (around 2 and 1.5) remained similar during 2020 compared with 2015-2019. Among patients with IJD, the risks of hospitalisation (0.5% vs 0.3% in their population referents), admission to intensive care (0.04% vs 0.03%) and death (0.10% vs 0.07%) due to COVID-19 were low. Antirheumatic drugs were not associated with increased risk of serious COVID-19 outcomes, although for certain drugs, precision was limited.

Conclusions: Risks of severe COVID-19-related outcomes were increased among patients with IJDs, but risk increases were also seen for non-COVID-19 morbidity. Overall absolute and excess risks are low and the level of risk increases are largely proportionate to those in the general population, and explained by comorbidities. With possible exceptions, antirheumatic drugs do not have a major impact on these risks.
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http://dx.doi.org/10.1136/annrheumdis-2021-219845DOI Listing
February 2021

Crystal structure determination of a lifelong biopersistent asbestos fibre using single-crystal synchrotron X-ray micro-diffraction.

IUCrJ 2021 Jan 1;8(Pt 1):76-86. Epub 2021 Jan 1.

Department of Chemical and Geological Sciences, University of Modena and Reggio Emilia, Modena, 41121, Italy.

The six natural silicates known as asbestos may induce fatal lung diseases inhalation, with a latency period of decades. The five amphibole asbestos species are assumed to be biopersistent in the lungs, and for this reason they are considered much more toxic than serpentine asbestos (chrysotile). Here, we refined the atomic structure of an amosite amphibole asbestos fibre that had remained in a human lung for ∼40 years, in order to verify the stability . The subject was originally exposed to a blend of chrysotile, amosite and crocidolite, which remained in his parietal pleura for ∼40 years. We found a few relicts of chrysotile fibres that were amorphous and magnesium depleted. Amphibole fibres that were recovered were undamaged and suitable for synchrotron X-ray micro-diffraction experiments. Our crystal structure refinement from a recovered amosite fibre demonstrates that the original atomic distribution in the crystal is intact and, consequently, that the atomic structure of amphibole asbestos fibres remains stable in the lungs for a lifetime; during which time they can cause chronic inflammation and other adverse effects that are responsible for carcinogenesis. The amosite fibres are not iron depleted proving that the iron pool for the formation of the asbestos bodies is biological (haemoglobin/plasma derived) and that it does not come from the asbestos fibres themselves.
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http://dx.doi.org/10.1107/S2052252520015079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7792997PMC
January 2021

Real-world 6 and 12-month Drug Retention, Remission and Response Rates of Secukinumab in 2,017 Psoriatic Arthritis patients in 13 European Countries.

Arthritis Care Res (Hoboken) 2021 Jan 18. Epub 2021 Jan 18.

Copenhagen Center for Arthritis Research (COPECARE), Center for Rheumatology and Spine Diseases, Centre for Head and Orthopaedics, Rigshospitalet, Glostrup, Denmark.

Objective: There is a lack of real-life studies on IL-17 inhibition in psoriatic arthritis (PsA). We assessed real-life 6-/12-month effectiveness (i.e. retention, remission, low-disease-activity [LDA] and response rates) of the IL-17 inhibitor secukinumab in PsA patients overall, and across 1) number of prior biologic/targeted synthetic Disease-Modifying Anti-Rheumatic Drugs (b/tsDMARDs), 2) years since diagnosis, and 3) European registries.

Methods: Thirteen quality registries in rheumatology participating in the European Spondyloarthritis Research Collaboration Network provided longitudinal, observational data collected as part of routine care, for secondary use. Data were pooled and analysed with Kaplan-Meier plots, log-rank tests, Cox regression, and multiple linear and logistic regression analyses.

Results: A total of 2,017 PsA patients started treatment with secukinumab between 2015 and 2018. Overall secukinumab retention rates were 86%/76% after 6/12 months. Crude (LUNDEX adjusted) 6-month remission/LDA (LDA including remission) rates for DAPSA28, DAS28-CRP and SDAI were 13%/46% (11%/39%), 36%/55% (30%/46%) and 13%/56% (11%/47%), and 12-month rates 11%/46% (7%/31%), 39%/56% (26%/38%) and 16%/62% (10%/41%), respectively. CDAI remission/LDA rates were similar to the SDAI rates. Six-month ACR20/50/70 responses were 34%/19%/11% (29%/16%/9%); 12-month: 37%/21%/11% (24%/14%/7%). Secukinumab effectiveness was significantly better for b/tsDMARD naïve patients, similar across time since diagnosis (<2/2-4/>4 years) and varied significantly across the European registries.

Conclusion: In this large real-world study on secukinumab treatment in PsA, 6- and 12-month effectiveness was comparable to previous observational studies of TNFi. Retention, remission, LDA and response rates were significantly better for b/tsDMARD naïve patients, independent of time since diagnosis and varied significantly across the European countries.
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http://dx.doi.org/10.1002/acr.24560DOI Listing
January 2021

Infection risk in sarcoidosis patients treated with methotrexate compared to azathioprine: A retrospective 'target trial' emulated with Swedish real-world data.

Respirology 2021 Jan 4. Epub 2021 Jan 4.

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

Background And Objective: No clinical trial has examined the risk of infection associated methotrexate and azathioprine, two advocated treatments for sarcoidosis. We aimed to compare the 6-month risk of infection after the initiation of methotrexate or azathioprine.

Methods: We conducted a retrospective target trial emulation using Swedish pre-existing data. We searched for eligible participants who were dispensed methotrexate or azathioprine in the Prescribed Drug Register (PDR) every day between January 2007 and June 2013. Adults were eligible if they had ≥2 ICD-coded visits for sarcoidosis in the National Patient Register (NPR) and were dispensed ≥1 systemic corticosteroid but no methotrexate or azathioprine in the past 6 months (PDR). Within 6 months of methotrexate or azathioprine initiation, diagnosis of infectious disease was identified (visit in the NPR where infectious disease was the primary diagnosis). We estimated RR and risk differences comparing methotrexate (n = 667) to azathioprine initiations (n = 259) using targeted maximum likelihood estimation (TMLE) adjusting for demographic factors, comorbidity and sarcoidosis severity proxies.

Results: There were 43 infections in the methotrexate group (adjusted 6-month risk 6.8%) and 29 infections in the azathioprine group (12.0%). The RR for infectious disease at 6 months associated with methotrexate compared to azathioprine initiation was 0.57 (95% CI: 0.39, 0.82) and the risk difference was -5.2% (95% CI: -8.5%, -1.8%). The RR at 9 months was attenuated to 0.77 (95% CI: 0.52, 1.14).

Conclusion: Methotrexate appears to be associated with a lower risk of infection in sarcoidosis than azathioprine, but randomized trials should confirm this finding.
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http://dx.doi.org/10.1111/resp.14001DOI Listing
January 2021

Comparison of treatment retention and response to secukinumab versus tumour necrosis factor inhibitors in psoriatic arthritis.

Rheumatology (Oxford) 2020 Dec 26. Epub 2020 Dec 26.

Parker Institute, Copenhagen University Hospital, Bispebjerg and Frederiksberg, Copenhagen, Denmark.

Objectives: To compare treatment retention and response to secukinumab vs adalimumab, including the other four TNF inhibitors (TNFi) as comparators, in PsA.

Methods: All patients with PsA starting secukinumab or a TNFi in 2015-2018 were identified in the biologic registers of the Nordic countries. Data on comorbidities were linked from national registers. One-year treatment retention and hazard ratios (HRs) for treatment discontinuation were calculated. The proportion achieving a 6 month 28-joint Disease Activity Index for Psoriatic Arthritis (DAPSA28) remission was determined together with odds ratios (ORs) for remission (logistic regression). Both HRs and ORs were calculated with adalimumab as the reference and adjusted for baseline characteristics and concurrent comorbidities. All analyses were stratified by the line of biologic treatment (first, second, third+).

Results: We identified 6143 patients contributing 8307 treatment courses (secukinumab, 1227; adalimumab, 1367). Secukinumab was rarely used as the first biologic, otherwise baseline characteristics were similar. No clinically significant differences in treatment retention or response rates were observed for secukinumab vs adalimumab. The adjusted HRs for discontinuation per the first, second and third line of treatment were 0.98 (95% CI 0.68, 1.41), 0.94 (0.70, 1.26) and 1.07 (0.84, 1.36), respectively. The ORs for DAPSA28 remission in the first, second and third line of treatment were 0.62 (95% CI 0.30, 1.28), 0.85 (0.41, 1.78) and 0.74 (0.36, 1.51), respectively. In the subset of patients previously failing a TNFi due to ineffectiveness, the results were similar.

Conclusion: No significant differences in treatment retention or response were observed between secukinumab and adalimumab, regardless of the line of treatment. This suggests that even in patients who have failed a TNFi, choosing either another TNFi or secukinumab may be equally effective.
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http://dx.doi.org/10.1093/rheumatology/keaa825DOI Listing
December 2020

One-year treatment outcomes of secukinumab versus tumor necrosis factor inhibitors in Spondyloarthritis.

Arthritis Care Res (Hoboken) 2020 Nov 30. Epub 2020 Nov 30.

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

Objective: To describe baseline characteristics and to compare treatment effectiveness of secukinumab versus tumor necrosis factor inhibitors (TNFi), in patients with spondyloarthritis (SpA) using adalimumab as the main comparator.

Methods: Observational, prospective cohort study. Patients with SpA (clinical ankylosing spondylitis/non-radiographic axial SpA/undifferentiated SpA) starting secukinumab or a TNFi during 2015-2018 were identified from five Nordic clinical rheumatology registries. Comorbidities and extra-articular manifestations (psoriasis/uveitis/inflammatory bowel disease) were captured from national registries (data available in 94% of patients) and included in multivariable analyses. We assessed 1-year treatment retention (crude survival curves, adjusted hazard ratios (HR) for treatment discontinuation) and 6-months' response-rates (ASDAS<2.1/BASDAI<40mm, crude/LUNDEX-adjusted, adjusted logistic-regression analyses with odds-ratio(OR)), stratified by line of biological treatment (1 /2 /3 +).

Results: In total, 10,853 treatment courses (842 secukinumab/10,011 TNFi whereof 1,977 adalimumab) were included. The proportion treated with secukinumab during 1 /2 /3 + was 1%/6%/22%). Extra-articular manifestations varied across treatments, while other baseline characteristics were largely similar. Secukinumab had a one-year retention comparable to adalimumab as 1 or 2 , but poorer as 3 + line of therapy (secukinumab 56% (51%-61%) versus adalimumab 70% (64%-75%)), adjusted HR 1.43 (1.12-1.81). Across treatment lines, secukinumab had poorer estimates for 6-months response rates than adalimumab, statistically significantly so only for 3 + line (adjusted analyses: ASDAS<2.1 OR=0.56 (0.35-0.90), BASDAI<40mm OR=0.62 (0.41-0.95)). Treatment outcomes varied across the five TNFi.

Conclusion: Secukinumab was mainly used in biologically experienced SpA patients. Secukinumab and adalimumab performed similar in patients who had failed a first biological, although with increasing prior biological exposure, adalimumab was superior.
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http://dx.doi.org/10.1002/acr.24523DOI Listing
November 2020

Deciphering Cancer Cell Behavior From Motility and Shape Features: Peer Prediction and Dynamic Selection to Support Cancer Diagnosis and Therapy.

Front Oncol 2020 20;10:580698. Epub 2020 Oct 20.

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

Cell motility varies according to intrinsic features and microenvironmental stimuli, being a signature of underlying biological phenomena. The heterogeneity in cell response, due to multilevel cell diversity especially relevant in cancer, poses a challenge in identifying the biological scenario from cell trajectories. We propose here a novel peer prediction strategy among cell trajectories, deciphering cell state (tumor vs. nontumor), tumor stage, and response to the anticancer drug etoposide, based on morphology and motility features, solving the strong heterogeneity of individual cell properties. The proposed approach first barcodes cell trajectories, then automatically selects the good ones for optimal model construction (good teacher and test sample selection), and finally extracts a collective response from the heterogeneous populations cooperative learning approaches, discriminating with high accuracy prostate noncancer vs. cancer cells of high vs. low malignancy. Comparison with standard classification methods validates our approach, which therefore represents a promising tool for addressing clinically relevant issues in cancer diagnosis and therapy, e.g., detection of potentially metastatic cells and anticancer drug screening.
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http://dx.doi.org/10.3389/fonc.2020.580698DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606946PMC
October 2020

The utility of assessing C-peptide in patients with insulin-treated type 2 diabetes: a cross-sectional study.

Acta Diabetol 2020 Nov 13. Epub 2020 Nov 13.

Unit of Endocrinology and Diabetes, Department of Medicine, Campus Bio-Medico University of Rome, Rome, Italy.

Aims: We aimed at evaluating residual β-cell function in insulin-treated patients with type 2 diabetes (T2D) while determining for the first time the difference in C-peptide level between patients on basal-bolus compared to those on the basal insulin scheme, considered as an early stage of insulin treatment, together with assessing its correlation with the presence of complications.

Methods: A total of 93 candidates with T2D were enrolled in this cross-sectional study and were categorized into two groups based on the insulin regimen: Basal-Bolus (BB) if on both basal and rapid acting insulin, and Basal (B) if on basal insulin only, without rapid acting injections. HbA1c, fasting C-peptide concentration and other metabolic parameters were recorded, as well as the patient medical history.

Results: The average fasting C-peptide was 1.81 ± 0.15 ng/mL, and its levels showed a significant inverse correlation with the duration of diabetes (r = -0.24, p = 0.03). Despite similar disease duration and metabolic control, BB participants displayed lower fasting C-peptide (p < 0.005) and higher fasting glucose (P = 0.01) compared with B patients. Concentrations below 1.09 ng/mL could predict the adoption of a basal-bolus treatment (Area 0.64, 95%CI:0.521-0.759, p = 0.038, sensitivity 45% and specificity 81%).

Conclusions: Insulin-treated patients with long-standing T2D showed detectable level of fasting C-peptide. Measuring the β-cell function may therefore guide toward effective therapeutic options when oral hypoglycemic agents prove unsuccessful.
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http://dx.doi.org/10.1007/s00592-020-01634-1DOI Listing
November 2020

Accelerating the experimental responses on cell behaviors: a long-term prediction of cell trajectories using Social Generative Adversarial Network.

Sci Rep 2020 09 24;10(1):15635. Epub 2020 Sep 24.

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

The incremented uptake provided by time-lapse microscopy in Organ-on-a-Chip (OoC) devices allowed increased attention to the dynamics of the co-cultured systems. However, the amount of information stored in long-time experiments may constitute a serious bottleneck of the experimental pipeline. Forward long-term prediction of cell trajectories may reduce the spatial-temporal burden of video sequences storage. Cell trajectory prediction becomes crucial especially to increase the trustworthiness in software tools designed to conduct a massive analysis of cell behavior under chemical stimuli. To address this task, we transpose here the exploitation of the presence of "social forces" from the human to the cellular level for motion prediction at microscale by adapting the potential of Social Generative Adversarial Network predictors to cell motility. To demonstrate the effectiveness of the approach, we consider here two case studies: one related to PC-3 prostate cancer cells cultured in 2D Petri dishes under control and treated conditions and one related to an OoC experiment of tumor-immune interaction in fibrosarcoma cells. The goodness of the proposed strategy has been verified by successfully comparing the distributions of common descriptors (kinematic descriptors and mean interaction time for the two scenarios respectively) from the trajectories obtained by video analysis and the predicted counterparts.
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http://dx.doi.org/10.1038/s41598-020-72605-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7519062PMC
September 2020

Lymphoma risks in patients with rheumatoid arthritis treated with biological drugs-a Swedish cohort study of risks by time, drug and lymphoma subtype.

Rheumatology (Oxford) 2021 02;60(2):809-819

Unit of Rheumatology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.

Objectives: To estimate the association between biological DMARDs (bDMARDs; overall and by drug) as used in RA and the risk of malignant lymphomas including subtypes.

Methods: By linking nationwide Swedish registers we identified cohorts of patients with RA initiating treatment with a bDMARD (n = 16 392), bDMARD-naïve (n = 55 253), an age- and sex-matched general population comparator cohort (n = 229 047), and all incident lymphomas 2001-16. We used Cox regression to calculate hazard ratios (HRs) of lymphoma taking calendar period and other factors into account.

Results: There were 82 lymphomas among the bDMARD-treated patients with RA, crude incidence rate 76/100 000 person-years, and 310 lymphomas among the bDMARD-naïve patients with RA, crude incidence rate 90/100 000 person-years. This resulted in an adjusted HR (aHR) associated with bDMARD treatment (vs not) of 1.08 (95% CI: 0.83, 1.41). The corresponding aHR for bDMARD-treated and bDMARD-naïve vs the general population was 1.65 (95% CI: 1.31, 2.08) and 1.56 (95% CI: 1.37, 1.78) respectively. Restricting follow-up period to after 2006, the aHR of lymphoma for patients with RA starting a first bDMARD vs bDMARD-naïve was 0.69 (95% CI: 0.47, 1.00), and for bDMARD treated vs patients with RA switching from one conventional synthetic DMARDs to another, aHR was 0.46 (95% CI: 0.28, 0.73). There were no signals of different risks with any particular TNF inhibitor (TNFi) agent. We found no different lymphoma subtype pattern following bDMARD therapy.

Conclusion: Treatment with bDMARDs, including both TNFi and non-TNFi bDMARDs, does not further increase the lymphoma risk in RA; instead, bDMARD treatment may actually reduce the excess lymphoma risk in RA.
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http://dx.doi.org/10.1093/rheumatology/keaa330DOI Listing
February 2021

Inflammatory hallmarks of lesser prominence in psoriatic arthritis patients starting biologics: a Nordic population-based cohort study.

Rheumatology (Oxford) 2021 01;60(1):140-146

Parker Institute, Copenhagen University Hospital, Bispebjerg and Frederiksberg, Copenhagen.

Objectives: To assess secular trends in baseline characteristics of PsA patients initiating their first or subsequent biologic DMARD (bDMARD) therapy and to explore prescription patterns and treatment rates of bDMARDs from 2006 to 2017 in the Nordic countries.

Methods: PsA patients registered in the Nordic rheumatology registries initiating any treatment with bDMARDs were identified. The bDMARDs were grouped as original TNF inhibitor [TNFi; adalimumab (ADA), etanercept (ETN) and infliximab (IFX)]; certolizumab pegol (CZP) and golimumab (GOL); biosimilars and ustekinumab, based on the date of release. Baseline characteristics were compared for the five countries, supplemented by secular trends with R2 calculations and point prevalence of bDMARD treatment.

Results: A total of 18 089 patients were identified (Denmark, 4361; Iceland, 449; Norway, 1948; Finland, 1069; Sweden, 10 262). A total of 54% of the patients were female, 34.3% of patients initiated an original TNFi, 8% CZP and GOL, 7.5% biosimilars and 0.3% ustekinumab as a first-line bDMARD. Subsequent bDMARDs were 25.2% original TNFi, 9% CZP and GOL, 12% biosimilars and 2.1% ustekinumab. From 2015 through 2017 there was a rapid uptake of biosimilars. The total of first-line bDMARD initiators with lower disease activity increased from 2006 to 2017, where an R2 close to 1 showed a strong association.

Conclusion: Across the Nordic countries, the number of prescribed bDMARDs increased from 2006 to 2017, indicating a previously unmet need for bDMARDs in the PsA population. In recent years, PsA patients have initiated bDMARDs with lower disease activity compared with previous years, suggesting that bDMARDs are initiated in patients with a less active inflammatory phenotype.
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http://dx.doi.org/10.1093/rheumatology/keaa237DOI Listing
January 2021

Discovering the hidden messages within cell trajectories using a deep learning approach for in vitro evaluation of cancer drug treatments.

Sci Rep 2020 05 6;10(1):7653. Epub 2020 May 6.

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

We describe a novel method to achieve a universal, massive, and fully automated analysis of cell motility behaviours, starting from time-lapse microscopy images. The approach was inspired by the recent successes in application of machine learning for style recognition in paintings and artistic style transfer. The originality of the method relies i) on the generation of atlas from the collection of single-cell trajectories in order to visually encode the multiple descriptors of cell motility, and ii) on the application of pre-trained Deep Learning Convolutional Neural Network architecture in order to extract relevant features to be used for classification tasks from this visual atlas. Validation tests were conducted on two different cell motility scenarios: 1) a 3D biomimetic gels of immune cells, co-cultured with breast cancer cells in organ-on-chip devices, upon treatment with an immunotherapy drug; 2) Petri dishes of clustered prostate cancer cells, upon treatment with a chemotherapy drug. For each scenario, single-cell trajectories are very accurately classified according to the presence or not of the drugs. This original approach demonstrates the existence of universal features in cell motility (a so called "motility style") which are identified by the DL approach in the rationale of discovering the unknown message in cell trajectories.
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http://dx.doi.org/10.1038/s41598-020-64246-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7203117PMC
May 2020

Risk of first and recurrent serious infection in sarcoidosis: a Swedish register-based cohort study.

Eur Respir J 2020 09 3;56(3). Epub 2020 Sep 3.

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

Serious infections impair quality of life and increase costs. Our aim was to determine if sarcoidosis is associated with a higher rate of serious infection and whether this varies by age, sex, time since diagnosis or treatment status around diagnosis.We compared individuals with sarcoidosis (at least two International Classification of Diseases codes in the Swedish National Patient Register 2003-2013; n=8737) and general population comparators matched 10:1 on age, sex and residential location (n=86 376). Patients diagnosed in 2006-2013 who were dispensed at least one immunosuppressant ±3 months from diagnosis (Swedish Prescribed Drug Register) were identified. Cases and comparators were followed in the National Patient Register for hospitalisations for infection. Using Cox and flexible parametric models, we estimated adjusted hazard ratios (aHR) and 95% confidence intervals for first and recurrent serious infections (new serious infection >30 days after previous).We identified 895 first serious infections in sarcoidosis patients and 3881 in comparators. The rate of serious infection was increased 1.8-fold in sarcoidosis compared to the general population (aHR 1.81, 95% CI 1.65-1.98). The aHR was higher in females than males and during the first 2 years of follow-up. Sarcoidosis cases treated with immunosuppressants around diagnosis had a three-fold increased risk, whereas nontreated patients had a 50% increased risk. The rate of serious infection recurrence was 2.8-fold higher in cases than in comparators.Serious infections are more common in sarcoidosis than in the general population, particularly during the first few years after diagnosis. Patients who need immunosuppressant treatment around diagnosis are twice as likely to develop a serious infection than those who do not.
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http://dx.doi.org/10.1183/13993003.00767-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7469972PMC
September 2020

Polylactic is a Sustainable, Low Absorption, Low Autofluorescence Alternative to Other Plastics for Microfluidic and Organ-on-Chip Applications.

Anal Chem 2020 05 21;92(9):6693-6701. Epub 2020 Apr 21.

Institute of Biological Chemistry, Biophysics and Bioengineering, School of Engineering and Physical Science, Heriot-Watt University, Edinburgh EH14 4AS, United Kingdom.

Organ-on-chip (OOC) devices are miniaturized devices replacing animal models in drug discovery and toxicology studies. The majority of OOC devices are made from polydimethylsiloxane (PDMS), an elastomer widely used in microfluidic prototyping, but posing a number of challenges to experimentalists, including leaching of uncured oligomers and uncontrolled absorption of small compounds. Here we assess the suitability of polylactic acid (PLA) as a replacement material to PDMS for microfluidic cell culture and OOC applications. We changed the wettability of PLA substrates and demonstrated the functionalization method to be stable over a time period of at least 9 months. We successfully cultured human cells on PLA substrates and devices, without coating. We demonstrated that PLA does not absorb small molecules, is transparent (92% transparency), and has low autofluorescence. As a proof of concept of its manufacturability, biocompatibility, and transparency, we performed a cell tracking experiment of prostate cancer cells in a PLA device for advanced cell culture.
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http://dx.doi.org/10.1021/acs.analchem.0c00651DOI Listing
May 2020

Authors' reply.

Scand J Rheumatol 2020 03;49(2):171-172

Department of Public Health and Clinical Medicine/Rheumatology, Umeå University, Umeå, Sweden.

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http://dx.doi.org/10.1080/03009742.2019.1701074DOI Listing
March 2020

A Camera Sensors-Based System to Study Drug Effects On In Vitro Motility: The Case of PC-3 Prostate Cancer Cells.

Sensors (Basel) 2020 Mar 10;20(5). Epub 2020 Mar 10.

Dept. Electronic Engineering, University of Rome Tor Vergata, 00133 Roma, Italy.

Cell motility is the brilliant result of cell status and its interaction with close environments. Its detection is now possible, thanks to the synergy of high-resolution camera sensors, time-lapse microscopy devices, and dedicated software tools for video and data analysis. In this scenario, we formulated a novel paradigm in which we considered the individual cells as a sort of sensitive element of a sensor, which exploits the camera as a transducer returning the movement of the cell as an output signal. In this way, cell movement allows us to retrieve information about the chemical composition of the close environment. To optimally exploit this information, in this work, we introduce a new setting, in which a cell trajectory is divided into sub-tracks, each one characterized by a specific motion kind. Hence, we considered all the sub-tracks of the single-cell trajectory as the signals of a virtual array of cell motility-based sensors. The kinematics of each sub-track is quantified and used for a classification task. To investigate the potential of the proposed approach, we have compared the achieved performances with those obtained by using a single-trajectory paradigm with the scope to evaluate the chemotherapy treatment effects on prostate cancer cells. Novel pattern recognition algorithms have been applied to the descriptors extracted at a sub-track level by implementing features, as well as samples selection (a good teacher learning approach) for model construction. The experimental results have put in evidence that the performances are higher when a further cluster majority role has been considered, by emulating a sort of sensor fusion procedure. All of these results highlighted the high strength of the proposed approach, and straightforwardly prefigure its use in lab-on-chip or organ-on-chip applications, where the cell motility analysis can be massively applied using time-lapse microscopy images.
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http://dx.doi.org/10.3390/s20051531DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7085768PMC
March 2020

Are infectious diseases risk factors for sarcoidosis or a result of reverse causation? Findings from a population-based nested case-control study.

Eur J Epidemiol 2020 Nov 11;35(11):1087-1097. Epub 2020 Feb 11.

Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Eugeniahemmet T2, 171 76, Stockholm, Sweden.

Findings from molecular studies suggesting that several infectious agents cause sarcoidosis are intriguing yet conflicting and likely biased due to their cross-sectional design. As done in other inflammatory diseases to overcome this issue, prospectively-collected register data could be used, but reverse causation is a threat when the onset of disease is difficult to establish. We investigated the association between infectious diseases and sarcoidosis to understand if they are etiologically related. We conducted a nested case-control study (2009-2013) using incident sarcoidosis cases from the Swedish National Patient Register (n = 4075) and matched general population controls (n = 40,688). Infectious disease was defined using inpatient/outpatient visits and/or antimicrobial dispensations starting 3 years before diagnosis/matching. Adjusted odds ratios (aOR) of sarcoidosis were estimated using conditional logistic regression and tested for robustness assuming the presence of reverse causation bias. The aOR of sarcoidosis associated with history of infectious disease was 1.19 (95% confidence interval [CI] 1.09, 1.29; 21% vs. 16% exposed cases and controls, respectively). Upper respiratory and ocular infections conferred the highest OR. Findings were similar when we altered the infection definition or varied the infection-sarcoidosis latency period (1-7 years). In bias analyses assuming one in 10 infections occurred because of preclinical sarcoidosis, the observed association was completely attenuated (aOR 1.02; 95% CI 0.90, 1.15). Our findings, likely induced by reverse causation due to preclinical sarcoidosis, do not support the hypothesis that common symptomatic infectious diseases are etiologically linked to sarcoidosis. Caution for reverse causation bias is required when the real disease onset is unknown.
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http://dx.doi.org/10.1007/s10654-020-00611-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695666PMC
November 2020

Consumption of Meat and Dairy Products Is Not Associated with the Risk for Rheumatoid Arthritis among Women: A Population-Based Cohort Study.

Nutrients 2019 Nov 19;11(11). Epub 2019 Nov 19.

Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, 171 77 Solna, Sweden.

Diet has gained attention as a risk factor for the development of rheumatoid arthritis (RA), especially with regards to food of animal origin, such as meat and dairy products. By using data from national patient registers and dietary data from a large prospective population cohort, the Swedish Mammography Cohort, we aimed to investigate whether the consumption of meat and dairy products had any impact on the risk of subsequent development of RA. During 12 years of follow-up (January 2003-December 2014; 381, 456 person-years), 368 patients with a new diagnosis of RA were identified. No associations between the development of RA and the consumption of meat and meat products (hazard ratio [HR] for the fully adjusted model: 1.08 [95% CI: 0.77-1.53]) or the total consumption of milk and dairy products (HR for the fully adjusted model: 1.09 [95% CI: 0.76-1.55]) were observed. In conclusion, in this large prospective cohort of women, no associations were observed between dietary intake of meat and dairy products and the risk of RA development.
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http://dx.doi.org/10.3390/nu11112825DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6893662PMC
November 2019

Treatment retention of infliximab and etanercept originators versus their corresponding biosimilars: Nordic collaborative observational study of 2334 biologics naïve patients with spondyloarthritis.

RMD Open 2019 23;5(2):e001079. Epub 2019 Oct 23.

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

Objective: Although clinical trials support equivalence of originator products and biosimilars for etanercept and infliximab, real-world studies among biologics-naïve patients with spondyloarthritis (SpA) are lacking. The objectives were to compare treatment retention in biologics-naïve patients with SpA starting either the originator product or a biosimilar of infliximab and etanercept, and to explore the baseline characteristics of these patients.

Methods: Patients with SpA (ankylosing spondylitis/non-radiographical axial SpA/undifferentiated SpA), starting infliximab or etanercept as their first-ever biological disease-modifying antirheumatic drug during January 2014-June 2017 were identified in five Nordic biologics-rheumatology registers. Baseline characteristics were retrieved from each registry; comorbidity data were identified through linkage to national health registers. Country-specific data were pooled, and data on infliximab and etanercept were analysed separately. Comparisons of treatment retention between originators and biosimilars were assessed through survival probability curves, retention rates (2 years for infliximab/1 year for etanercept) and Hazard Ratios (HR).

Results: We included 1319 patients starting infliximab (24% originator/76% biosimilar), and 1015 patients starting etanercept (49% originator/51% biosimilar). Baseline characteristics were largely similar for the patients treated with the originators compared with the corresponding biosimilars. Survival probability curves were highly similar for the originator and its biosimilar, as were retention rates: infliximab 2-year retention originator, 44% (95% CI 38% to 50%)/biosimilar, 46% (95% CI: 42% to 51%); and etanercept 1-year retention originator, 66% (95% CI 61% to 70%)/biosimilar, 73% (95% CI 68% to 78%). HRs were not statistically significant.

Conclusion: This observational study of biologics-naïve patients with SpA from five Nordic countries showed similar baseline characteristics and very similar retention rates in patients treated with originators versus biosimilars, for both infliximab and etanercept, indicating comparable effectiveness in clinical practice.
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http://dx.doi.org/10.1136/rmdopen-2019-001079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6827791PMC
April 2020

Development of a Sensor Node for Remote Monitoring of Plants.

Sensors (Basel) 2019 Nov 8;19(22). Epub 2019 Nov 8.

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

The appraisal of stress in plants is of great relevance in agriculture and any time the transport of living plants is involved. Wireless sensor networks (WSNs) are an optimal solution to simultaneously monitor a large number of plants in a mostly automatic way. A number of sensors are readily available to monitor indicators that are likely related to stress. The most common of them include the levels of total volatile compounds and CO together with common physical parameters such as temperature, relative humidity, and illumination, which are known to affect plants' behavior. Recent progress in microsensors and communication technologies, such as the LoRa protocol, makes it possible to design sensor nodes of high sensitivity where power consumption, transmitting distances, and costs are optimized. In this paper, the design of a WSN dedicated to plant stress monitoring is described. The nodes have been tested on European privet () kept in completely different conditions in order to induce opposite level of stress. The results confirmed the relationship between the release of total Volatile Organic Compounds (VOCs) and the environmental conditions. A machine learning model based on recursive neural networks demonstrates that total VOCs can be estimated from the measure of the environmental parameters.
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http://dx.doi.org/10.3390/s19224865DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6891448PMC
November 2019

Characterization and assessment of the potential toxicity/pathogenicity of fibrous glaucophane.

Environ Res 2019 11 4;178:108723. Epub 2019 Sep 4.

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

In California, the metamorphic blueschist occurrences within the Franciscan Complex are commonly composed of glaucophane, which can be found with a fibrous habit. Fibrous glaucophane's potential toxicity/pathogenicity has never been determined and it has not been considered by the International Agency for Research on Cancer (IARC) as a potential carcinogen to date. Notwithstanding, outcrops hosting fibrous glaucophane are being excavated today in California for building/construction purposes (see for example the Calaveras Dam Replacement Project - CDRP). Dust generated by these excavation activities may expose workforces and the general population to this potential natural hazard. In this work, the potential toxicity/pathogenicity of fibrous glaucophane has been determined using the fibre potential toxicity index (FPTI). This model has been applied to a representative glaucophane-rich sample collected at San Anselmo, Marin County (CA, USA), characterized using a suite of experimental techniques to determine morphometric, crystal-chemical parameters, surface reactivity, biodurability and related parameters. With respect to the asbestos minerals, the FPTI of fibrous glaucophane is remarkably higher than that of chrysotile, and comparable to that of tremolite, thus supporting the application of the precautionary approach when excavating fibrous glaucophane-rich blueschist rocks. Because fibrous glaucophane can be considered a potential health hazard, just like amphibole asbestos, it should be taken into consideration in the standard procedures for the identification and assessment of minerals fibres in soil and air samples.
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http://dx.doi.org/10.1016/j.envres.2019.108723DOI Listing
November 2019

Structure Model and Toxicity of the Product of Biodissolution of Chrysotile Asbestos in the Lungs.

Chem Res Toxicol 2019 10 10;32(10):2063-2077. Epub 2019 Sep 10.

Department of Engineering "Enzo Ferrari" , The University of Modena and Reggio Emilia , Via P. Vivarelli 10 , I-41125 Modena , Italy.

Asbestos is a commercial term indicating six natural silicates with asbestiform crystal habit. Of these, five are double-chain silicates (amphibole) and one is a layer silicate (serpentine asbestos or chrysotile). Although all species are classified as human carcinogens, their degree of toxicity is still a matter of debate. Amphibole asbestos species are biopersistent in the human lungs and exert their chronic toxic action for decades, whereas chrysotile is not biopersistent and transforms into an amorphous silica structure prone to chemical/physical clearance when exposed to the acidic environment created by the alveolar macrophages. There is evidence in the literature of the toxicity of chrysotile, but its limited biopersistence is thought to explain the difference in toxicity with respect to amphibole asbestos. To date, no comprehensive model describing the toxic action of chrysotile in the lungs is available, as the structure and toxic action of the product formed by the biodissolution of chrysotile are unknown. This work is aimed at fulfilling this gap and explaining the toxic action in terms of structural, chemical, and physical properties. We show that chrysotile's fibrous structure induces cellular damage, mainly through physical interactions. Based on our previous work and novel findings, we propose the following toxicity model: inhaled chrysotile fibers exert their toxicity in the alveolar space by physical and biochemical action. The fibers are soon leached by the intracellular acid environment into a product with residual toxicity, and the dissolution process liberates toxic metals in the intracellular and extracellular environment.
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http://dx.doi.org/10.1021/acs.chemrestox.9b00220DOI Listing
October 2019

Treatment response and drug retention rates in 24 195 biologic-naïve patients with axial spondyloarthritis initiating TNFi treatment: routine care data from 12 registries in the EuroSpA collaboration.

Ann Rheum Dis 2019 11 20;78(11):1536-1544. Epub 2019 Aug 20.

EuroSpA Coordinating Center, Copenhagen Center for Arthritis Research (COPECARE), Center for Rheumatology and Spine Diseases, Centre for Head and Orthopaedics, Rigshospitalet, Glostrup, Denmark.

Objective: To study drug retention and response rates in patients with axial spondyloarthritis (axSpA) initiating a first tumour necrosis factor inhibitor (TNFi).

Methods: Data from 12 European registries, prospectively collected in routine care, were pooled. TNFi retention rates (Kaplan-Meier statistics), Ankylosing Spondylitis Disease Activity Score (ASDAS) Inactive disease (<1.3), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) <40 mm and Assessment of SpondyloArthritis International Society responses (ASAS 20/40) were assessed at 6, 12 and 24 months.

Results: A first TNFi was initiated in 24 195 axSpA patients. Heterogeneity of baseline characteristics between registries was observed. Twelve-month retention was 80% (95% CI 79% to 80%), ranging from 71% to 94% across registries. At 6 months, ASDAS Inactive disease/BASDAI<40 rates were 33%/72% (LUNDEX-adjusted: 27%/59%), ASAS 20/40 response rates 64%/49% (LUNDEX-adjusted 52%/40%). In patients initiating first TNFi after 2009, 6097 patients was registered to fulfil ASAS criteria for axSpA, 2935 was registered to fulfil modified New York Criteria for Ankylosing Spondylitis and 1178 patients was registered as having non-radiographic axSpA. In nr-axSpA patients, we observed lower 12-month retention rates (73% (70%-76%)) and lower 6-month LUNDEX adjusted response rates (ASDAS Inactive disease/BASDAI40 20%/50%, ASAS 20/40 45%/33%). For patients initiating first TNFi after 2014, 12-month retention rate, but not 6-month response rate, was numerically higher compared with patients initiating TNFi in 2009-2014.

Conclusion: A large European database of patients with axSpA initiating a first TNFi treatment in routine care, demonstrated that 27% of patients achieved ASDAS inactive disease after 6 months, while 59% achieved BASDAI <40. Four of five patients continued treatment after 1 year.
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http://dx.doi.org/10.1136/annrheumdis-2019-215427DOI Listing
November 2019

Postsurgical Ultrasound Evaluation of Patients with Prosthesis in Acellular Dermal Matrix: Results from Monocentric Experience.

Int J Surg Oncol 2019 16;2019:7437324. Epub 2019 Jun 16.

Department of Plastic and Reconstructive Surgery, "Sapienza" University of Rome, V.le Regina Elena 324, 00161 Rome, Italy.

Mastectomy and breast prosthetic reconstruction is the most common surgical treatment for women diagnosed with breast cancer. In the last few years, breast prosthetic augmentation in acellular dermal matrix (ADM) has been introduced. The aim of this study is to present our single-center experience in evaluating the outcome of patients who underwent breast reconstruction in ADM, using ultrasound (US) examination. US follow-up allows evaluating both normal postoperative findings and changes and potential local complications, demonstrating that ADM is a safe option for women candidates for mastectomy.
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http://dx.doi.org/10.1155/2019/7437324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6601478PMC
November 2019

Emery-Dreifuss muscular dystrophy type 4: A new mutation associated with hypertrophic cardiomyopathy masked by a perinatal distress-related spastic diplegia.

Clin Case Rep 2019 May 21;7(5):1078-1082. Epub 2019 Apr 21.

Clinical Genetic Unit Fondazione IRCCS Casa Sollievo della Sofferenza San Giovanni Rotondo Italy.

Hypertrophic cardiomyopathy could be part of a more complex syndrome like Emery-Dreifuss muscular dystrophy type 4. Genetic analysis allowed to identify a de novo heterozygous missense mutation in SYNE1 gene (chr6:152665253:G > C), supporting physician to reach a correct diagnosis in patient affected by cardiomyopathy associated with a difficult clinical scenario.
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http://dx.doi.org/10.1002/ccr3.2140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6509902PMC
May 2019

The influence of spatial and temporal resolutions on the analysis of cell-cell interaction: a systematic study for time-lapse microscopy applications.

Sci Rep 2019 05 1;9(1):6789. Epub 2019 May 1.

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

Cell-cell interactions are an observable manifestation of underlying complex biological processes occurring in response to diversified biochemical stimuli. Recent experiments with microfluidic devices and live cell imaging show that it is possible to characterize cell kinematics via computerized algorithms and unravel the effects of targeted therapies. We study the influence of spatial and temporal resolutions of time-lapse videos on motility and interaction descriptors with computational models that mimic the interaction dynamics among cells. We show that the experimental set-up of time-lapse microscopy has a direct impact on the cell tracking algorithm and on the derived numerical descriptors. We also show that, when comparing kinematic descriptors in two diverse experimental conditions, too low resolutions may alter the descriptors' discriminative power, and so the statistical significance of the difference between the two compared distributions. The conclusions derived from the computational models were experimentally confirmed by a series of video-microscopy acquisitions of co-cultures of unlabelled human cancer and immune cells embedded in 3D collagen gels within microfluidic devices. We argue that the experimental protocol of acquisition should be adapted to the specific kind of analysis involved and to the chosen descriptors in order to derive reliable conclusions and avoid biasing the interpretation of results.
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http://dx.doi.org/10.1038/s41598-019-42475-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6494897PMC
May 2019