Publications by authors named "Leonardo Punzi"

249 Publications

The forward-looking advertising. Description of a gouty heart in an advertisement published in 1919.

Joint Bone Spine 2022 May 10;89(5):105398. Epub 2022 May 10.

Institute for the History of Rheumatology, Venice, Italy; President Italian Society of Rheumatology, Italy.

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http://dx.doi.org/10.1016/j.jbspin.2022.105398DOI Listing
May 2022

Acute Calcium Pyrophosphate Crystal Arthritis of the Wrist Elicited by Anti-COVID-19 Vaccination After Carpal Tunnel Release.

Am J Case Rep 2022 Mar 12;23:e934833. Epub 2022 Mar 12.

Plastic and Reconstructive Surgery Unit, Padua University Hospital, Padua, Italy.

BACKGROUND Calcium pyrophosphate dihydrate deposition disease includes a variety of clinical syndromes, including acute calcium pyrophosphate (CPP) crystal arthritis. Most patients with CPP crystal arthritis have a primary/idiopathic form presenting with severe pain, swelling, and stiffness. COVID-19 infection, which originated in China in December 2019, required extraordinary efforts to develop and test new vaccines to halt the pandemic. The Vaxzervria vaccine has shown excellent safety and efficacy in phase 3 trials with a mechanism based on the expression of the SARS-CoV-2 spike protein gene coding for the S-antigen, which stimulates the immune response. CASE REPORT We describe an acute event of crystal arthritis after a carpal tunnel syndrome release followed by administration of the second dose of anti-COVID-19 Vaccine Oxford-AstraZeneca (ChAdOx1 nCoV-19). Medical treatment resulted in full resolution of the symptoms in 2 weeks. CONCLUSIONS Although most episodes of acute arthritis happen spontaneously, certain factors may trigger the acute CPP crystal arthritis such as intercurrent illnesses or surgeries. Although the association between carpal tunnel syndrome and CPP arthritis has been known for over 40 years, surgical release of the carpal ligament has always been associated with full resolution of symptoms. This is the first case report describing an exacerbation after carpal canal release, concomitant with the administration of the vaccine. According to our opinion, the vaccination associated with a prior surgery in the same anatomical site could have synergically triggered the arthritis flare-up, in a predisposed patient, with a mechanism still unknown.
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http://dx.doi.org/10.12659/AJCR.934833DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8924853PMC
March 2022

A Pro-Inflammatory Signature Constitutively Activated in Monogenic Autoinflammatory Diseases.

Int J Mol Sci 2022 Feb 5;23(3). Epub 2022 Feb 5.

Center for Gout and Bone & Joint Metabolic Diseases, SS Giovanni & Paolo Hospital, 30122 Venice, Italy.

Autoinflammatory diseases (AIDs) are disorders characterised by recurrent inflammatory episodes in charge of different organs with no apparent involvement of autoantibodies or antigen-specific T lymphocytes. Few common clinical features have been identified among all monogenic AIDs (mAIDs), while the search for a common molecular pattern is still ongoing. The aim of this study was to increase knowledge on the inflammatory pathways in the development of mAIDs in order to identify possible predictive or diagnostic biomarkers for each disease and to develop future preventive and therapeutic strategies. Using protein array-based systems, we evaluated two signalling pathways known to be involved in inflammation and a wide range of inflammatory mediators (pro-inflammatory cytokines and chemokines) in a cohort of 23 patients affected by different mAIDs, as FMF, TRAPS, MKD, Blau syndrome (BS), and NLRP12D. Overall, we observed upregulation of multiple signalling pathway intermediates at protein levels in mAIDs patients' PBMCs, compared with healthy controls, with significant differences also between patients. FMF, TRAPS, and BS presented also peculiar activations of inflammatory pathways that can distinguish them. MAPK pathway activation, however, seems to be a common feature. The serum level of cytokines and chemokines produced clear differences between patients with distinct diseases, which can help distinguish each autoinflammatory disease. The FMF cytokine production profile appears broader than that of TRAPS, which, in turn, has higher cytokine levels than BS. Our findings suggest an ongoing subclinical inflammation related to the abnormal and constitutive signalling pathways and define an elevated inflammatory cytokine signature. Moreover, the upregulation of Th17-related cytokines emphasises the important role for Th17 and/or Th17-like cells also in monogenic AIDs.
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http://dx.doi.org/10.3390/ijms23031828DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8836675PMC
February 2022

Venice and its role in the history of cardiovascular medicine.

Nutr Metab Cardiovasc Dis 2021 07 26;31(8):2512-2513. Epub 2021 May 26.

Institute of History of Rheumatology, Venice - Italian Society of Rheumatology, Italy.

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http://dx.doi.org/10.1016/j.numecd.2021.05.008DOI Listing
July 2021

Polydatin Prevents Calcium Pyrophosphate Crystal-Induced Arthritis in Mice.

Nutrients 2021 Mar 13;13(3). Epub 2021 Mar 13.

Department of Surgery, Oncology and Gastroenterology-DISCOG, University of Padova, 35128 Padova, Italy.

Background: Polydatin is a stilbenoid with important antioxidant, anti-inflammatory, and immunomodulating properties. The aim of this study was to assess the anti-inflammatory preventive effect of polydatin in the mouse model of acute arthritis induced by calcium pyrophosphate (CPP) crystals.

Methods: Acute arthritis was induced by the injection of a suspension of sterile CPP crystals into the ankle joint of Balb/c mice. Animals were randomized to receive polydatin or colchicine (the control drug) according to a prophylactic and a therapeutic protocol. The primary outcome was the variation of ankle swelling obtained after crystal injection and treatment, while histological parameters such as leukocyte infiltration, IL-1ß and CXCL1 levels and tissue expression were considered as secondary outcomes.

Results: Prophylactic treatment with PD significantly diminished ankle swelling after 48 h from crystal injection. Secondary outcomes such as leukocyte infiltration, necrosis, edema, and synovitis were also decreased. PD caused a reduction in circulating levels of IL-1ß and CXCL1, as well as their tissue expression. By contrast, the therapeutic administration of PD did not have any beneficial effect.

Conclusions: PD can effectively prevent acute inflammatory response to crystals in the mouse model of CPP crystal-induced arthritis. These results suggest that this bioactive compound might be used in the prevention of crystal-induced acute attacks in humans.
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http://dx.doi.org/10.3390/nu13030929DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7998880PMC
March 2021

NKG2D ligands in inflammatory joint diseases: analysis in human samples and mouse models.

Clin Exp Rheumatol 2021 Sep-Oct;39(5):982-987. Epub 2021 Jan 8.

Université de Strasbourg, INSERM, ImmunoRhumatologie Moléculaire UMR_S 1109, Fédération de Médecine Translationnelle de Strasbourg, Faculté de Médecine, Strasbourg, and Fédération Hospitalo-Universitaire, OMICARE, Centre de Recherche d'Immunologie et d'Hématologie, Strasbourg, France.

Objectives: NKG2D ligands (NKG2DLs) are stress-inducible molecules involved in multiple inflammatory settings. In this work, we quantified MICA, an NKG2DL, in the synovial fluid of patients suffering various arthritides and measured Nkg2dLs gene expression in murine models of acute joint inflammation.

Methods: Soluble MICA (sMICA) was quantified by ELISA is synovial fluids harvested from patients suffering osteoarthritis, rheumatoid arthritis, psoriatic arthritis, calcium pyrophosphate crystal arthritis, urate crystal arthritis and reactive arthritis. Transcripts encoding murine NKG2DLs were quantified by RT-qPCR in the joints of mouse models of rheumatoid arthritis, urate crystal arthritis and osteoarthritis.

Results: Marked overproduction of sMICA was observed in the synovial fluid of RA patients. Mouse studies highlighted the complex transcriptional regulation of Nkg2d ligands encoding genes depending on the inflammatory setting and microenvironment CONCLUSIONS: sMICA quantification could be an interesting biomarker to identify acute inflammation in RA patients in whom classical markers (i.e. anti-citrullinated protein antibodies, ACPA) are undetectable.
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http://dx.doi.org/10.55563/clinexprheumatol/klc3h6DOI Listing
September 2021

Effect of pathogenic crystals on the production of pro- and anti-inflammatory cytokines by different leukocyte populations.

Immunobiology 2021 01 26;226(1):152042. Epub 2020 Nov 26.

Faculty of Medicine, University of Geneva, Switzerland.

Purpose: To evaluate cytokine production in vitro by different types of leukocytes stimulated with monosodium urate (MSU), calcium pyrophosphate (CPP) and basic calcium phosphate (BCP) crystals.

Material And Methods: Polymorphonuclear cells (PMN), monocytes and lymphocytes, isolated from healthy volunteer blood, were stimulated for different time periods with increasing MSU, CPP or BCP crystal concentrations. IL-1β, IL-8, IL-6, CCL2, IL-1Ra and TGFβ1 were determined by ELISA.

Results: Exposure of PMN to different crystals resulted in a moderate IL-8 and IL-1Ra release. Stimulation of monocytes induced a significant production of all the cytokines evaluated. The highest levels of IL-1β, IL-6, CCL2 and IL-8 were observed with MSU at 0.5 mg/ml, CPP at 0.01-0.05 mg/ml and BCP at 1 mg/ml after 18-48 h and then decreased. At the same crystal concentrations, IL-1Ra and TGFβ1 increased until the end of the experiment. Treatment of lymphocytes with different crystals did not induce cytokine release.

Conclusion: This study demonstrates that PMN, monocytes and lymphocytes from the same donor respond differently after stimulation with MSU, CPP or BCP crystals, depending on the dose and the time of exposure. Crystals induce a rapid increase of pro-inflammatory cytokines, whereas longer time is required to release high levels of anti-inflammatory cytokines.
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http://dx.doi.org/10.1016/j.imbio.2020.152042DOI Listing
January 2021

One year in review 2020: gout.

Clin Exp Rheumatol 2020 Sep-Oct;38(5):807-821. Epub 2020 Oct 2.

Rheumatology Unit, Department of Medicine - DIMED, University of Padova, ltaly.

Gout is the most prevalent form of inflammatory arthritis, with a strong impact on individual health and healthcare systems. This article reviews clinical and experimental evidences about gout emerged throughout the 2019. Starting with an epidemiological analysis, the review explores new insights on genetic factors influencing the development of gout flare, pathogenetic mechanisms, risk factors for the disease and comorbidities. An overview on pharmacological therapies and recent knowledge on the impact of lifestyle and dietary habits are also included. Finally, the review contains a novel section on animal models, which reflects the renewed interest of researchers in the acute process triggered by monosodium urate crystals.
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October 2020

Validation of the Italian Version of the Educational Needs Assessment Tool in Rheumatoid Arthritis Patients and Factors Associated with Educational Needs.

J Pers Med 2020 Oct 1;10(4). Epub 2020 Oct 1.

Rheumatology Unit, Department of Medicine (DIMED), University of Padova, 35128 Padova, Italy.

The educational needs assessment tool (ENAT) is a seven-domain questionnaire assessing the educational needs (EN) of patients with rheumatoid arthritis (RA). The aim of this study was to validate the Italian version of the ENAT and to identify factors associated with EN in people with RA. The original English ENAT version was translated into Italian according to Beaton's method and subjected to Rasch analysis for validity testing. Socio-demographic and clinical variables were tested for associations with the ENAT domain scores using a multivariable linear regression model. The ENAT translated well into Italian and retained its construct validity. Some adjustments were needed when pooling the Italian and English datasets. The overall score of the ENAT had a high median: 82.8 (interquartile range (IQR): 57.5 to 100) i.e., 72.4% of the maximum score. The highest score was observed in the domain "Arthritis process" and the lowest was in "Support systems". Only gender was independently associated with EN (females having higher EN than males). The Italian ENAT is feasible for the use in the clinical setting and may help the health care practitioners to tailor educational interventions for RA patients. The characteristics of the patients, particularly female gender, may be associated with higher EN.
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http://dx.doi.org/10.3390/jpm10040150DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7712017PMC
October 2020

Criterion validity of ultrasound in the identification of calcium pyrophosphate crystal deposits at the knee: an OMERACT ultrasound study.

Ann Rheum Dis 2021 02 28;80(2):261-267. Epub 2020 Sep 28.

Rheumatology Department, University of Medicine and Pharmacy of Craiova, Craiova, Romania.

Objective: To evaluate the discriminatory ability of ultrasound in calcium pyrophosphate deposition disease (CPPD), using microscopic analysis of menisci and knee hyaline cartilage (HC) as reference standard.

Methods: Consecutive patients scheduled for knee replacement surgery, due to osteoarthritis (OA), were enrolled. Each patient underwent ultrasound examination of the menisci and HC of the knee, scoring each site for presence/absence of CPPD. Ultrasound signs of inflammation (effusion, synovial proliferation and power Doppler) were assessed semiquantitatively (0-3). The menisci and condyles, retrieved during surgery, were examined microscopically by optical light microscopy and by compensated polarised microscopy. CPPs were scored as present/absent in six different samples from the surface and from the internal part of menisci and cartilage. Ultrasound and microscopic analysis were performed by different operators, blinded to each other's findings.

Results: 11 researchers from seven countries participated in the study. Of 101 enrolled patients, 68 were included in the analysis. In 38 patients, the surgical specimens were insufficient. The overall diagnostic accuracy of ultrasound for CPPD was of 75%-sensitivity of 91% (range 71%-87% in single sites) and specificity of 59% (range 68%-92%). The best sensitivity and specificity were obtained by assessing in combination by ultrasound the medial meniscus and the medial condyle HC (88% and 76%, respectively). No differences were found between patients with and without CPPD regarding ultrasound signs of inflammation.

Conclusion: Ultrasound demonstrated to be an accurate tool for discriminating CPPD. No differences were found between patents with OA alone and CPPD plus OA regarding inflammation.
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http://dx.doi.org/10.1136/annrheumdis-2020-217998DOI Listing
February 2021

The role of clinical inertia in suboptimal management of gout.

Authors:
Leonardo Punzi

Swiss Med Wkly 2020 Aug 19;150:w20334. Epub 2020 Aug 19.

Centre for Gout, and Bone and Joint Metabolic Diseases, Rheumatology Unit, Hospital SS Giovanni e Paolo, Venice, Italy.

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http://dx.doi.org/10.4414/smw.2020.20334DOI Listing
August 2020

Efficacy of conservative treatments for hand osteoarthritis : An umbrella review of interventional studies.

Wien Klin Wochenschr 2021 Mar 30;133(5-6):234-240. Epub 2020 Jun 30.

Centre for Gout and Metabolic Bone and Joint Diseases, Rheumatology, SS Giovanni and Paolo Hospital, Venice, Italy.

Background: Hand osteoarthritis (OA) is common, but the efficacy/safety of treatment interventions aimed to improve health outcomes in this population are not well understood. Therefore, the aim of this study was to map and grade the effect of interventions for health outcomes in hand OA.

Methods: Umbrella review of systematic reviews with meta-analyses of randomized controlled trials (RCTs) using placebo/no intervention as control group. For outcomes with a p-value <0.05, the certainty of the evidence was evaluated using the grading of recommendations assessment, development and evaluation (GRADE) assessment.

Results: From 189 abstracts, 9 meta-analyses (24 outcomes) were included, with 8 reporting significant summary results. The use of splints was associated with reduced pain at medium term in thumb carpometacarpal OA (standardized mean difference [SMD] = -0.70; 95% confidence intervals [95% CI]: -1.05 to -0.35; low certainty), reduced pain in long follow-up RCTs in symptomatic hand OA (SMD = -0.80; 95% CI: -1.16; -0.45; moderate certainty), and better function (SMD = 0.42; 95% CI: 0.08; 0.70; low certainty). The use of resistance training (SMD = -0.27; 95% CI: -0.47; -0.07) or physical exercise (SMD = -0.23; 95% CI: -0.42; -0.04) in improving hand pain and in improving finger joint stiffness (SMD = -0.36; 95%CI: -0.58; -0.15) was supported by a moderate certainty of evidence. The use of intra-articular hyaluronic acid in improving function (MD = 1.12; 95% CI: 0.61; 1.64; moderate certainty of evidence) was the only statistically significant pharmacological intervention.

Conclusion: Only some non-pharmacological interventions are effective in improving health outcomes in hand OA and this evidence is supported by a moderate/low certainty, indicating the necessity of further interventional research.
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http://dx.doi.org/10.1007/s00508-020-01702-0DOI Listing
March 2021

Effectiveness of steroid injection for hand psoriatic dactylitis: results from a multicentre prospective observational study.

Clin Rheumatol 2020 Nov 16;39(11):3383-3392. Epub 2020 May 16.

Rheumatology Unit, Department of Clinical Medicine and Surgery, University Federico II, via Sergio Pansini 5, 80131, Naples, Italy.

Objective: To assess the effectiveness of steroid injection (local treatment, LT) into the digital flexor tendon sheath of dactylitis in psoriatic arthritis (PsA) patients as compared with systemic treatment (ST).

Methods: Forty-six PsA patients with a total of 73 dactylitic fingers were assessed in an observational, multicentre, prospective study by the Leeds Dactylitis Index basic (LDI-b) score and evaluated for local pain (visual analogue scale-VAS pain) and functional impairment (VAS-FI). Steroid injection was proposed to all patients. Patients refusing LT were treated with oral NSAIDs. Both the groups continued baseline csDMARDs and/or corticosteroids therapy. The clinical outcomes were measured at baseline, 1 month (T1) and 3 months (T3).

Results: The reduction of VAS-pain, VAS-FI and LDI-b values was statistically significant higher in the LT group (24 patients, 38 dactylitic fingers) as compared with the ST group (22 patients, 35 dactylitic fingers), both at T1 (p < 0.001, p < 0.001 and p = 0.008, respectively) and at T3 (p < 0.001, p < 0.001 and p < 0.001, respectively). A clinically meaningful treatment response (defined as a contemporary reduction of at least 5 points in VAS-pain and VAS-FI or as values of VAS-pain and VAS-FI were both ≤ 2) was observed at T1 in 33 (87%) digits in LT group and in 6 (17%) digits in ST group (p < 0.001). At T3, clinical response improved significantly in both the groups, with significant difference (94% vs 31%, p < 0.001).

Conclusions: For the first time, we show the effectiveness of steroid injection into the digital flexor tendon sheath in improving clinical aspects of hand psoriatic dactylitis. Key Points • Therapy with steroid injection (local treatment, LT), into the digital flexor tendon sheath for the treatment of active dactylitis in psoriatic arthritis patients, is more effective when compared with systemic treatment (ST) alone. • The reduction of VAS-pain, VAS-functional impairment (VAS-FI) and Leeds Dactylitis Index basic values was statistically significant higher in the LT group as compared with the ST group, both at T1and at T3. • A clinically meaningful response was observed at T1 in 87% of digits of patients treated with steroid injection and in 17% of digits of the systemic treatment group (p < 0.001). At T3, clinical response improved significantly in both the groups, with significant difference. • For the first time, findings from this study show that the use of steroid injections into the digital flexor tendon sheath for psoriatic dactylitis could be an effective and safe first-line therapy for psoriatic dactylitis.
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http://dx.doi.org/10.1007/s10067-020-05142-zDOI Listing
November 2020

Biologics in the treatment of calcium pyrophosphate deposition disease: a systematic literature review.

Clin Exp Rheumatol 2020 Sep-Oct;38(5):1001-1007. Epub 2020 Apr 28.

Rheumatology Unit, Department of Clinical and Molecular Sciences, Polytechnic University of Marche, Carlo Urbani Hospital, Jesi, Ancona, Italy.

The main aim of this systematic literature review (SLR) was to summarise the evidence in the use of biological therapies in calcium pyrophosphate deposition disease (CPPD). We performed a SLR using PubMed, Embase and Cochrane databases. Only studies reporting the efficacy of biologics in CPPD were selected. The search resulted in 83 articles; 11 were further evaluated in the SLR. Seventy-six patients were included: 2 received infliximab, whereas 74 anakinra. Anakinra was used in refractory disease (85.1%) or in patients with contraindications to standard treatments (23.0%). Clinical response to anakinra was observed in 80.6% of patients with acute and 42.9% of those with chronic CPPD. Short-term treatment was well tolerated and adverse events were reported in 4.1% of the cases. This review provides evidence in favour of the use of anakinra as a therapeutic option in patients with CPPD, especially in acute refractory CPPD or when standard treatments are contraindicated.
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October 2020

The two faces of the same medal… or maybe not? Comparing osteoarthritis and calcium pyrophosphate deposition disease: a laboratory and ultrasonographic study.

Clin Exp Rheumatol 2021 Jan-Feb;39(1):66-72. Epub 2020 Apr 9.

Section of Rheumatology, Department of Medical Sciences, University of Ferrara, Italy.

Objectives: Osteoarthritis (OA) and calcium pyrophosphate deposition disease (CPPD) are frequently associated but the real relation between these diseases is not still understood. The aim of this paper is to investigate the characteristics in terms of inflammation, anatomical changes and synovial fluid (SF) features in knees of patients with OA and CPPD.

Methods: Consecutive patients older than 55 years with knee pain and swelling were enrolled. All patients underwent a complete clinical examination, a US examination of the affected joint, arthrocentesis of the knee and analysis of synovial fluid, including dosing of inorganic ions and number of crystals. The gold standard for the diagnosis was the microscopic analysis of the SF.

Results: Sixty-seven patients were enrolled, 25 affected by OA and 42 by CPPD. At US, a significantly higher amount of effusion and synovitis was identified in patients with CPPD but there were no significant differences regarding structural changes. At the SF analysis, the white blood cell (WBC) count was higher in patients with CPPD who also presented a higher number of polymorphonuclear cells and a lower number of monocytes. Regarding the inorganic ion concentration, the statistical analysis did not reveal any differences. The number of crystals in the SF, correlated with a larger effusion, higher grade of synovitis and a higher WBC count.

Conclusions: A higher degree of inflammation was found in patients with CPPD. The findings suggest that longitudinal studies would be useful to better understand the evolution of the diseases and highlight the need for different treatment strategies.
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February 2021

Multiple Dimensions of Self-Esteem and Their Relationship with Health in Adolescence.

Int J Environ Res Public Health 2020 04 11;17(8). Epub 2020 Apr 11.

Health and Motion Venice Association (HEMOVE), 30122 Venice, Italy.

The aim of the present study was to examine how different domains of self-esteem (social, competence, affect, academic, family, and physical) relate to self-reported physical and mental health, lower back pain (LBP), smoking, and physical exercise in a sample of adolescents. A sample of 326 adolescents 14-19 years old completed several self-report questionnaires collecting epidemiological data, and information on their LBP, smoking, and physical exercise, the Short Form Health Survey (SF-36), and the Multidimensional Self-Concept Scale. Pearson's correlations were calculated between their self-esteem scores and their physical and mental health scores. Three multivariate analyses of variance (MANOVAs) were performed to estimate associations between self-esteem and LBP, smoking, and physical exercise. Self-esteem (total and subcomponent scores) correlated positively with physical and mental health, and with physical exercise, and negatively with smoking. The results also confirm gender-related differences in self-esteem, in favor of boys. This study offers the first findings on the relationship between different domains of self-esteem and a variety of health outcomes in an adolescent population. The results suggest that multidimensional interventions could be devised to improve adolescents' physical health by promoting their physical exercise, and to prevent their smoking by nurturing their self-esteem.
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http://dx.doi.org/10.3390/ijerph17082616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7215662PMC
April 2020

A long-term nationwide study on mortality associated to rheumatoid arthritis in Italy.

Clin Exp Rheumatol 2020 Nov-Dec;38(6):1223-1226. Epub 2020 Mar 28.

Integrated System for Health, Social Assistance, Welfare and Justice, Italian National Institute of Statistics (ISTAT), Italy.

Objectives: We aimed to evaluate trends of rheumatoid arthritis (RA) mortality reported as the underlying cause of death (UCD) and as multiple causes of death (MCD) in Italy between 2003 and 2015.

Methods: Analyses were carried out on the Italian National Cause of Death Register, managed by the Italian National Institute of Statistics (ISTAT). Deaths from January 1, 2003 to December 31, 2015 with any mention of RA were included. Diseases are coded according to the International Classification of Diseases, 10th Edition (ICD- 10, 2009 version). Time trends of age-standardised rates were analysed for RA both as UCD and MCD, and the annual percent change (APC) was estimated.

Results: Overall, 26,564 deaths with a mention of RA were retrieved out of 7,595,214 deaths (0.35% of all certificates). The mention of RA as MCD increased throughout the study period, meanwhile the selection as the UCD decreased. RA mortality rates based on the UCD declined (males APC -3.1%, CI -3.9, -2.3; females APC -3.3%, CI -4.1, -2.4); while rates based on the MCD were stable. Specifically, rates were stable or declined among younger subjects and increased in subjects aged ≥80 years.

Conclusions: RA was found to be increasingly reported in death certificates in the last two decades in Italy, although it is less frequently reported as the UCD. Due to the increased survival of patients, we observed a shift of RA-related mortality towards the elderly, making RA a comorbidity contributing to death in these patients.
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December 2020

Levels of inflammatory cytokines and metalloproteinases are increased in knee synovial fluid of patients with concomitant erosive hand osteoarthritis.

Clin Exp Rheumatol 2020 Jul-Aug;38(4):800. Epub 2020 Feb 14.

Centre for Gout and Metabolic Bone and Joint Diseases, Rheumatology, SS Giovanni and Paolo Hospital, Venice, Italy.

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September 2020

Improvement of Function and Its Determinants in a Group of Axial Spondyloarthritis Patients Treated with TNF Inhibitors: A Real-Life Study.

Rheumatol Ther 2020 Jun 15;7(2):301-310. Epub 2020 Feb 15.

Day Hospital di Reumatologia, ASST Centro Specialistico Ortopedico Traumatologico G. Pini-CTO, Milano, Italy.

Introduction: The aim of this work is to investigate the improvement of physical function and its determinants in axial spondyloarthritis (SpA) patients treated with tumor necrosis factor (TNF) inhibitors in a real clinical practice setting.

Methods: An observational study was conducted in patients with axial SpA treated with anti-TNF from 2010 to 2018 with a minimum 6 months of follow-up. All patients fulfilled ASAS or the modified New York criteria. The Bath Ankylosing Spondylitis Metrology Index (BASMI) and the Bath Ankylosing Spondylitis Functional Index (BASFI) were used as objective and self-reported functional indices. The improvement of function and factors associated were evaluated for the present study, as well as disease activity and patient-reported outcome measures.

Results: A total of 183 patients with axial SpA were examined. Among them, 27 were non-radiographic axial SpA, while the remaining 156 were ankylosing spondylitis patients. BASFI and BASMI significantly improved during follow-up. Improvement of metrology index BASMI inverse correlated with disease duration (rho - 0.2, p = 0.009) and directly correlated with the improvement of BASDAI (rho 0.26, p = 0.003) and CRP (rho 0.26, p = 0.0003). Improvement of BASFI significantly inversely correlated with disease duration and directly correlated with the improvement of BASDAI, CRP, and baseline ESR. Male sex, lower disease duration, high ESR, and the improvement of BASDAI were found to be associated with the improvement of BASFI.

Conclusions: Our results showed that in real-life settings, patients improve in BASMI and BASFI. Furthermore, factors associated with this improvement were identified.
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http://dx.doi.org/10.1007/s40744-020-00197-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7211226PMC
June 2020

Polydatin and Resveratrol Inhibit the Inflammatory Process Induced by Urate and Pyrophosphate Crystals in THP-1 Cells.

Foods 2019 Nov 7;8(11). Epub 2019 Nov 7.

Rheumatology Unit, Department of Medicine-DIMED, University of Padova, 35128 Padova, Italy.

Resveratol (RES) and its natural precursor polydatin (PD) are polyphenols that may display a broad variety of beneficial effects including anti-inflammatory properties. This study aimed to investigate the role of RES and PD in the inflammatory process induced by monosodium urate (MSU) and calcium pyrophosphate (CPP) crystals in vitro. A monocytic cell line (THP-1) was primed for 3 hours with phorbol myristate acetate (100 ng/mL) and stimulated with synthetic MSU (0.05 mg/mL) and CPP (0.025 mg/mL) crystals. RES and PD were added to cultures concurrently with the crystals, or as 2-hour pretreatment. The effect of the two polyphenols was evaluated on intracellular and extracellular IL-1β levels, NACHT-LRRPYD-containing protein-3 (NLRP3) inflammasome expression, reactive oxygen species (ROS) and nitric oxide (NO) production, and the assessment of crystal phagocytosis. RES and PD strongly inhibited IL-1β induced by crystals after cell pretreatment. Cell pretreatment was effective also in reducing IL-1 mRNA expression while no effect was observed on NLRP3 gene expression. RES and PD had no effect on crystal phagocytosis when used as pretreatment. Both polyphenols were significantly effective in inhibiting ROS and NO production. Our results demonstrated that RES and PD are effective in inhibiting crystal-induced inflammation. Data obtained after cell pretreatment allow us to hypothesize that these polyphenols act on specific signaling pathways, preventing inflammation.
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http://dx.doi.org/10.3390/foods8110560DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6915461PMC
November 2019

Mud-bath treatment of seronegative spondyloarthritis: experience at the Euganean Thermal Area.

Int J Biometeorol 2020 Jun 24;64(6):937-941. Epub 2019 Jul 24.

Rheumatology Unit, Department of Medicine DIMED, University of Padova, Padua, Italy.

Mud-bath therapy (MBT) has been used as a treatment for rheumatic diseases and musculoskeletal complaints in the Euganean Thermal Area (near Padova, Italy) since ancient time. There is no consensus about the use of MBT in patients with inflammatory rheumatic diseases, although experimental studies have suggested a beneficial effect of MBT on chronic articular inflammation. To evaluate the effects of MBT in patients affected by seronegative spondyloarthritis, very common chronic inflammatory rheumatic diseases, randomized controlled trials (RCT) performed in the Euganean Thermal Area have been reviewed. A significant improvement of spondylitis parameters was observed in enteropathic spondylitis, without bowel symptom exacerbation. A long-term amelioration of clinical evaluation indices was found in ankylosing spondylitis. A significant improvement of cutaneous lesions, arthritis activity, and patient's functional ability was observed in psoriatic arthritis. MBT was usually well tolerated and adverse side effects were rarely reported. The review of the RCT suggests that MBT may exert additional beneficial effects in patients with seronegative spondyloarthritis treated with pharmacological therapy.
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http://dx.doi.org/10.1007/s00484-019-01761-7DOI Listing
June 2020

Late-Onset and Elderly Psoriatic Arthritis: Clinical Aspects and Management.

Drugs Aging 2019 10;36(10):909-925

Rheumatology Unit, Department of Clinical Medicine and Surgery, School of Medicine, University of Naples Federico II, Via S. Pansini 5, 80131, Naples, Italy.

Psoriatic arthritis (PsA) can start in subjects aged over 60 years, defined as late-onset PsA. In late-onset PsA, the weight of family history and genetic background appears less significant when compared with younger onset PsA, whereas obesity and smoking have been suggested as potential risk factors. In patients with late-onset PsA, erosive polyarticular or oligoarticular patterns are more frequent than other phenotypes. Laboratory findings usually show an increase in levels of acute phase reactants, including erythrocyte sedimentation rate and C-reactive protein. The drugs used for the management of young PsA subjects represent the same therapeutic armamentarium used in patients with late-onset disease. However, in elderly subjects, these anti-inflammatory, immunomodulatory and immunosuppressive therapies, including newer biologic therapies, represent an important challenge due to age aspects, increased frequency of comorbidities and associated polypharmacotherapy. There is a need for more evidence around treatment strategy for these patients in order to identify the best balance between the benefits and risks of pharmacological agents. This is important for establishing how treatment should ideally be tailored to the characteristics of any single patient and to the presence of complex age- and disease-related aspects. The objective of this review is to focus on pathogenetic, clinical and therapeutic aspects of late-onset PsA and the management of elderly PsA patients.
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http://dx.doi.org/10.1007/s40266-019-00688-3DOI Listing
October 2019

2018 updated European League Against Rheumatism evidence-based recommendations for the diagnosis of gout.

Ann Rheum Dis 2020 01 5;79(1):31-38. Epub 2019 Jun 5.

Rheumatology, Assistance Publique - Hopitaux de Paris, Paris, France.

Although gout is the most common inflammatory arthritis, it is still frequently misdiagnosed. New data on imaging and clinical diagnosis have become available since the first EULAR recommendations for the diagnosis of gout in 2006. This prompted a systematic review and update of the 2006 recommendations. A systematic review of the literature concerning all aspects of gout diagnosis was performed. Recommendations were formulated using a Delphi consensus approach. Eight key recommendations were generated. A search for crystals in synovial fluid or tophus aspirates is recommended in every person with suspected gout, because demonstration of monosodium urate (MSU) crystals allows a definite diagnosis of gout. There was consensus that a number of suggestive clinical features support a clinical diagnosis of gout. These are monoarticular involvement of a foot or ankle joint (especially the first metatarsophalangeal joint); previous episodes of similar acute arthritis; rapid onset of severe pain and swelling; erythema; male gender and associated cardiovascular diseases and hyperuricaemia. When crystal identification is not possible, it is recommended that any atypical presentation should be investigated by imaging, in particular with ultrasound to seek features suggestive of MSU crystal deposition (double contour sign and tophi). There was consensus that a diagnosis of gout should not be based on the presence of hyperuricaemia alone. There was also a strong recommendation that all people with gout should be systematically assessed for presence of associated comorbidities and risk factors for cardiovascular disease, as well as for risk factors for chronic hyperuricaemia. Eight updated, evidence-based, expert consensus recommendations for the diagnosis of gout are proposed.
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http://dx.doi.org/10.1136/annrheumdis-2019-215315DOI Listing
January 2020

Pro-inflammatory adipokine profile in psoriatic arthritis: results from a cross-sectional study comparing PsA subset with evident cutaneous involvement and subset "sine psoriasis".

Clin Rheumatol 2019 Sep 30;38(9):2547-2552. Epub 2019 May 30.

Rheumatology Unit, Department of Clinical Medicine and Surgery, School of Medicine, University Federico II of Naples, Via S. Pansini 5, 80131, Naples, Italy.

Objective: Adipokines have been considered in the pathogenesis of the inflammatory processes of psoriatic arthritis (PsA). The main aim of the current study is to investigate possible differences and correlations between adipokines and clinical expression in PsA patients with and without clinical evident psoriasis.

Methods: Serum levels of TNF-α, IL-6, leptin, resistin, visfatin, and ghrelin were measured in 80 consecutive PsA patients, 42 PsA patients with clinically evident psoriasis (group 1) and 38 PsA patients sine psoriasis (group 2), fulfilling the CASPAR criteria.

Results: Patients of the two groups were not significantly different for levels of TNF-α, IL-6, leptin, resistin, visfatin, and ghrelin. In the entire cohort, a positive association has been shown between leptin levels and female gender (β = 0.3, p = 0.001), BMI (β = 0.8, p < 0.0001), tender joint count (β = 0.23, p = 0.05), and patient pain-VAS score (β = 0.4, p = 0.049). In group 1, serum concentration of leptin was associated with female gender (β = 0.41, p < 0.0001) and BMI (β = 0.6, p = 0.012), whereas in group 2, a positive association was shown between leptin levels and BMI (β = 0.7, p = 0.003) and CRP (β = 0.35, p = 0.012). With regard to resistin, in the multivariate model, only the association between resistin and IL-6 was found (β = 0.33, p = 0.002). The association between resistin and IL-6 was confirmed in group 1 (β = 0.46, p = 0.004) but not in group 2.

Conclusions: Until today, the present study represents the first investigating difference in the adipokine pattern between PsA patients with psoriasis and sine psoriasis. We report a strict interplay between leptin, female gender, BMI, and inflammatory activity in overall PsA patients. In PsA patients with clinical evident psoriasis, leptin was associated with female gender and BMI, and a close association between resistin and IL-6 was found. Further, a positive association between leptin levels and BMI and CRP was found in PsA sine psoriasis patients. Further studies are also advocated for clarifying the possible role of these adipokines as laboratory findings or as disease mediators in addressing the different phenotypes of the disease. Key Points •Levels of TNF-α, IL-6, leptin, resistin, visfatin, and ghrelin did not differ between PsA patients with clinical evident psoriasis and PsA sine psoriasis. •There is a strict interplay between leptin, female gender, BMI, and inflammatory activity in PsA. •There is a close association between resistin and IL-6 in PsA patients with clinical evident psoriasis.
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http://dx.doi.org/10.1007/s10067-019-04619-wDOI Listing
September 2019

IgE-mediated mast cell activation promotes inflammation and cartilage destruction in osteoarthritis.

Elife 2019 05 14;8. Epub 2019 May 14.

GRECC, VA Palo Alto Health Care System, Palo Alto, United States.

Osteoarthritis is characterized by articular cartilage breakdown, and emerging evidence suggests that dysregulated innate immunity is likely involved. Here, we performed proteomic, transcriptomic, and electron microscopic analyses to demonstrate that mast cells are aberrantly activated in human and murine osteoarthritic joint tissues. Using genetic models of mast cell deficiency, we demonstrate that lack of mast cells attenuates osteoarthritis in mice. Using genetic and pharmacologic approaches, we show that the IgE/FcεRI/Syk signaling axis is critical for the development of osteoarthritis. We find that mast cell-derived tryptase induces inflammation, chondrocyte apoptosis, and cartilage breakdown. Our findings demonstrate a central role for IgE-dependent mast cell activation in the pathogenesis of osteoarthritis, suggesting that targeting mast cells could provide therapeutic benefit in human osteoarthritis.

Editorial Note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter).
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http://dx.doi.org/10.7554/eLife.39905DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6516833PMC
May 2019

Health-related quality of life, illness perception, coping strategies and the distribution of dependency in autoinflammatory diseases.

Clin Exp Rheumatol 2019 Nov-Dec;37 Suppl 121(6):156-157. Epub 2019 Apr 26.

Department of Medicine, DIMED, University of Padova, Italy.

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January 2020

Effect of nutritional supplementations on physical performance and muscle strength parameters in older people: A systematic review and meta-analysis.

Ageing Res Rev 2019 05 28;51:48-54. Epub 2019 Feb 28.

National Research Council, Neuroscience Institute, Aging Branch, Padova, Italy.

Malnutrition plays a role in the development of poor physical performance, frailty and sarcopenia. The use of nutritional supplementations for improving physical performance and muscle strength parameters in older people is unclear. We therefore aimed to summarize the effect of nutritional supplementations compared to placebo on physical performance (i.e. tests more investigating physical function, utilising aerobic capacity & muscle power) and muscle strength (i.e. tests depending on muscle power) outcomes in older people in randomized controlled trials (RCTs). A literature search in major databases was undertaken until the 01st September 2018. Eligible studies were RCTs investigating the effect of nutritional supplementations vs. placebo in older people (people having an age >60 years). Standardized mean differences (SMD) and 95% confidence intervals (CIs) were used through a random effect model. Over 4007 potentially eligible articles, 32 RCTs for a total of 4137 older participants (2097 treated and 2040 placebo) (mean age: 76.3 years; 65% females) were included. Compared to placebo, multi-nutrient supplementations significantly improved chair rise time (n = 3; SMD=-0.90; 95%CI: -1.46 to -0.33; I = 87%). Multi-nutrients significantly improved handgrip strength when compared to placebo (n = 6; 780 participants; SMD = 0.41; 95%CI: 0.06 to 0.76; I = 79%), as did nutritional supplementations including protein (n = 7; 535 participants; SMD = 0.24; 95%CI: 0.07 to 0.41; I = 16%).Nutritional supplementations also led to a significant improvement in chair rise time and in handgrip strength in participants affected by frailty/sarcopenia and in those affected by medical conditions. In conclusion, nutritional supplementation can improve a number of physical performance outcomes in older people, particularly when they include multi-nutrients and in people already affected by specific medical conditions, or by frailty/sarcopenia.
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http://dx.doi.org/10.1016/j.arr.2019.02.005DOI Listing
May 2019

Editorial: IL-1 Inhibition.

Front Pharmacol 2019 12;10:87. Epub 2019 Feb 12.

Faculty of Medicine, University of Geneva, Geneva, Switzerland.

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http://dx.doi.org/10.3389/fphar.2019.00087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6379779PMC
February 2019

Periodontal Injection of Lipopolysaccharide Promotes Arthritis Development in Mice.

Inflammation 2019 Jun;42(3):1117-1128

Centre for Gout and Metabolic Bone and Joint Diseases, Rheumatology, SS Giovanni and Paolo Hospital, Venice, Italy.

This study evaluated the arthritogenic effect of lipopolysaccharide (LPS) in a mouse model of periodontal disease. Periodontitis was induced in wild-type CD1 mice by nine LPS injections (10 or 50 ng) into the maxillary mucosa. Untreated mice or injected with LPS at the tail were used as controls. Two weeks after final inoculation, mice were sacrificed to collect blood, maxilla, and paw samples. Development and progression of periodontitis and arthritis were monitored using clinical assessment, micro-computed tomography (micro-CT), ultrasound (US), and histological analysis. CXCL1, IL-1β, IL-6, TNF-α, and anti-citrullinated peptide antibodies (ACPA) serum levels were determined by enzyme immunoassay. Ankle swelling and inflammation manifested after the 5th periodontal injection of 50 ng of LPS and progressed until the end of experiments. Periodontal injection of 10 ng of LPS and LPS tail injection did not induce paw changes. Therefore, the subsequent assessments were conducted only in mice periodontally injected with 50 ng of LPS. Maxillary micro-CT and histological analysis showed that LPS-induced alveolar bone resorption and vascular proliferation in periodontal tissue, but not inflammation. US and histology revealed increased joint space, leukocyte infiltration, synovial proliferation, and mild cartilage and bone destruction in the paws of mice orally injected. Cytokines and ACPA showed a trend towards an increase in LPS mice. This study shows that arthritis and periodontal disease can co-occur in wild-type mice after periodontal injection of LPS at optimal dose. Our model may be useful to improve the understanding of the mechanisms linking periodontitis and arthritis.
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http://dx.doi.org/10.1007/s10753-019-00975-6DOI Listing
June 2019
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