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Article: Editorial: New insights into pathophysiology and management of pregnancy in systemic autoimmune diseases: Toward new therapeutic approaches.

Bettiol, Alessandra / Ramires de Jesús, Guilherme / Haase, Isabell / Andreoli, Laura / Urban, Maria Letizia

2022 Volume 13, Page(s) 1017067

Language	English
Publishing date	2022-10-06
Publishing country	Switzerland
Document type	Editorial
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2022.1017067
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Article: SIRT1 and thrombosis.

Bettiol, Alessandra / Urban, Maria Letizia / Emmi, Giacomo / Galora, Silvia / Argento, Flavia Rita / Fini, Eleonora / Borghi, Serena / Bagni, Giacomo / Mattioli, Irene / Prisco, Domenico / Fiorillo, Claudia / Becatti, Matteo

Frontiers in molecular biosciences

2024 Volume 10, Page(s) 1325002

Abstract: Thrombosis is a major cause of morbidity and mortality worldwide, with a complex and multifactorial pathogenesis. Recent studies have shown that SIRT1, a member of the sirtuin family of NAD + -dependent deacetylases, plays a crucial role in regulating ... ...

Abstract	Thrombosis is a major cause of morbidity and mortality worldwide, with a complex and multifactorial pathogenesis. Recent studies have shown that SIRT1, a member of the sirtuin family of NAD + -dependent deacetylases, plays a crucial role in regulating thrombosis, modulating key pathways including endothelial activation, platelet aggregation, and coagulation. Furthermore, SIRT1 displays anti-inflammatory activity both
Language	English
Publishing date	2024-01-18
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2814330-9
ISSN	2296-889X
ISSN	2296-889X
DOI	10.3389/fmolb.2023.1325002
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Article ; Online: Long-term outcome of a cohort of Italian patients affected with alpha-Mannosidosis.

Bertolini, Anna / Rigoldi, Miriam / Cianflone, Annalia / Mariani, Raffaella / Piperno, Alberto / Canonico, Francesco / Cefalo, Graziella / Carubbi, Francesca / Simonati, Alessandro / Urban, Maria Letizia / Beccari, Tommaso / Parini, Rossella

Clinical dysmorphology

2023 Volume 33, Issue 1, Page(s) 1–8

Abstract: Alpha-mannosidosis (MIM #248500) is an ultra-rare autosomal recessive lysosomal storage disease with multi-system involvement and a wide phenotypic spectrum. Information on long-term outcomes remains poor. We present the long-term outcomes (median, 19 ... ...

Abstract	Alpha-mannosidosis (MIM #248500) is an ultra-rare autosomal recessive lysosomal storage disease with multi-system involvement and a wide phenotypic spectrum. Information on long-term outcomes remains poor. We present the long-term outcomes (median, 19 years) of nine patients with alpha-mannosidosis, three females and six males, followed at a single center. The findings of the nine patients were collected from medical records and reported as mean ± SD or median, and range. The age of onset of the first symptoms ranged from 0-1 to 10 years. The diagnostic delay ranged from 2 to 22 years (median= 11 years). Coarse face, hearing, heart valves, joints, gait, language, dysarthria, psychiatric symptoms, I.Q., MRI, walking disabilities, orthopedic disturbances and surgeries showed a slow worsening over the decades. Our patients showed a slowly worsening progressive outcome over the decades. Psychiatric symptoms were present in 100% of our population and improved with the appropriate pharmacological intervention. This aspect requires attention when following up on these patients. Our description of the long-term evolution of alpha-mannosidosis patients may provide basic knowledge for understanding the effects of specific treatments.
MeSH term(s)	Male ; Female ; Humans ; Infant, Newborn ; Infant ; Child, Preschool ; Child ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; alpha-Mannosidosis/diagnosis ; Delayed Diagnosis ; Mental Disorders ; Inheritance Patterns ; Italy/epidemiology
Language	English
Publishing date	2023-11-23
Publishing country	England
Document type	Journal Article
ZDB-ID	1121482-x
ISSN	1473-5717 ; 0962-8827
ISSN (online)	1473-5717
ISSN	0962-8827
DOI	10.1097/MCD.0000000000000474
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Article ; Online: Prevalence and clinical associations of ultrasound-confirmed enthesitis in systemic lupus erythematosus.

Fagni, Filippo / Bettiol, Alessandra / Silvestri, Elena / Fedi, Roberto / Palermo, Adalgisa / Urban, Maria Letizia / Mazzotta, Ruggero / Malandrino, Danilo / Bello, Federica / Mattioli, Irene / Simon, David / Di Scala, Gerardo / Schett, Georg / Prisco, Domenico / Emmi, Giacomo

Rheumatology (Oxford, England)

2023 Volume 62, Issue 11, Page(s) 3619–3626

Abstract: Objectives: To assess the prevalence of US-confirmed enthesitis in a cohort of patients with SLE and to analyse the clinical associations to enthesitis during the course of SLE.: Methods: In a retrospective analysis of the SLE cohort of the Lupus ... ...

Abstract	Objectives: To assess the prevalence of US-confirmed enthesitis in a cohort of patients with SLE and to analyse the clinical associations to enthesitis during the course of SLE. Methods: In a retrospective analysis of the SLE cohort of the Lupus Unit of the Careggi University Hospital, US examinations of SLE patients presenting with tender and/or swollen joints were retrieved to assess the presence of enthesitis. Patients with US-proven enthesitis were compared with SLE controls with tender and/or swollen joints who showed no US evidence of enthesitis. Clinical and laboratory features were compared at disease onset and during follow-up. Results: A total of 400 patients fulfilling EULAR/ACR classification criteria for SLE were assessed. Of these, 106 underwent articular US examination. Evidence of enthesitis was found in 31/106 (29.2%) patients. Seventy-one patients without US-enthesitis were included as controls; four were excluded due to lack of follow-up data. Laboratory and clinical features were comparable between cases and controls at disease onset. Throughout a median follow-up of 10.0 (interquartile range [IQR] 8.3-23.3) years for cases and 12.4 (IQR 7.2-13.3) years for controls, patients with enthesitis were less likely to develop renal involvement (22.6% vs 46.5%, P = 0.028) and failed B cell depletion more frequently (75.0% vs 0%). Conclusion: In SLE patients with clinically active joints, US-proven enthesitis is a fairly common finding. Enthesitis in SLE could be the hallmark of a distinct disease phenotype with less renal involvement, more arthritis and low response to anti-CD 20 therapy, potentially requiring a tailored treatment.
MeSH term(s)	Humans ; Retrospective Studies ; Prevalence ; Lupus Erythematosus, Systemic/complications ; Lupus Erythematosus, Systemic/diagnostic imaging ; Lupus Erythematosus, Systemic/epidemiology ; Joints ; Arthritis/complications ; Enthesopathy/diagnostic imaging ; Enthesopathy/epidemiology ; Enthesopathy/etiology
Language	English
Publishing date	2023-03-20
Publishing country	England
Document type	Journal Article
ZDB-ID	1464822-2
ISSN	1462-0332 ; 1462-0324
ISSN (online)	1462-0332
ISSN	1462-0324
DOI	10.1093/rheumatology/kead123
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Article ; Online: Pharmacological Interventions for the Prevention of Fetal Growth Restriction: A Systematic Review and Network Meta-Analysis.

Bettiol, Alessandra / Avagliano, Laura / Lombardi, Niccolò / Crescioli, Giada / Emmi, Giacomo / Urban, Maria Letizia / Virgili, Gianni / Ravaldi, Claudia / Vannacci, Alfredo

Clinical pharmacology and therapeutics

2021 Volume 110, Issue 1, Page(s) 189–199

Abstract: The prevention of fetal growth restriction (FGR) is challenging in clinical practice. To date, no meta-analysis summarized evidence on the relative benefits and harms of pharmacological interventions for FGR prevention. We performed a systematic review ... ...

Abstract	The prevention of fetal growth restriction (FGR) is challenging in clinical practice. To date, no meta-analysis summarized evidence on the relative benefits and harms of pharmacological interventions for FGR prevention. We performed a systematic review and network meta-analysis (NetMA), searching PubMed, Embase, Cochrane Library, and ClinicalTrials.gov from inception until November 2019. We included clinical trials and observational studies on singleton gestating women evaluating antiplatelet, anticoagulant, or other treatments, compared between each other or with controls (placebo or no treatment), and considering the pregnancy outcome FGR (primary outcome of the NetMA). Secondary efficacy outcomes included preterm birth, placental abruption, and fetal or neonatal death. Safety outcomes included bleeding and thrombocytopenia. Network meta-analyses using a frequentist framework were conducted to derive odds ratios (ORs) and 95% confidence intervals (CIs). Of 18,780 citations, we included 30 studies on 4,326 patients. Low molecular weight heparin (LMWH), alone or associated with low-dose aspirin (LDA), appeared more efficacious than controls in preventing FGR (OR 2.00, 95% CI 1.27-3.16 and OR 2.67, 95% CI 1.21-5.89 for controls vs. LMWH and LDA + LMWH, respectively). No difference between active treatments emerged in terms of FGR prevention, but estimates for treatments other than LMWH +/- LDA were imprecise. Only the confidence in the evidence regarding LMWH vs. controls was judged as moderate, according to the Confidence in Network Meta-Analysis framework. No treatment was associated with an increased risk of bleeding, although estimates were precise enough only for LMWH. These results should inform clinicians on the benefits of active pharmacological prophylaxis for FGR prevention.
Language	English
Publishing date	2021-02-26
Publishing country	United States
Document type	Journal Article
ZDB-ID	123793-7
ISSN	1532-6535 ; 0009-9236
ISSN (online)	1532-6535
ISSN	0009-9236
DOI	10.1002/cpt.2164
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Article ; Online: Evidence of subclinical atherosclerosis in eosinophilic granulomatosis with polyangiitis.

Bello, Federica / Bettiol, Alessandra / Silvestri, Elena / Mattioli, Irene / Urban, Maria Letizia / Palermo, Adalgisa / Mazzetti, Matteo / Malandrino, Danilo / Calcaterra, Ilenia / Vaglio, Augusto / Di Minno, Matteo Nicola Dario / Emmi, Giacomo / Prisco, Domenico

Rheumatology (Oxford, England)

2022 Volume 62, Issue 2, Page(s) 835–840

Abstract: Objectives: Patients affected by eosinophilic granulomatosis with polyangiitis (EGPA) display an increased risk of atherothrombotic events compared with the general population. An increased frequency of subclinical markers of atherosclerosis has been ... ...

Abstract	Objectives: Patients affected by eosinophilic granulomatosis with polyangiitis (EGPA) display an increased risk of atherothrombotic events compared with the general population. An increased frequency of subclinical markers of atherosclerosis has been observed in other ANCA-associated vasculitis, but no specific study focused on EGPA. We therefore evaluated subclinical atherosclerosis in EGPA patients and in a control population. Methods: Forty EGPA patients and 80 controls matched by age, sex and traditional cardiovascular risk factors underwent sonographic assessment of common carotid artery (CCA) intima-media thickness (IMT). The presence of plaques of the CCA was also investigated. The correlation between CCA-IMT and clinical and laboratory features was also assessed. Results: Median CCA-IMT was significantly higher in EGPA patients compared with controls (P = 0.002). Also, the proportion of subjects with increased CCA-IMT and with presence of plaques was significantly higher among EGPA patients (P < 0.001 for both). Moreover, within the EGPA cohort, CCA-IMT tended to increase with disease duration (P = 0.034) and corticosteroid cumulative dose (P = 0.004). No significant associations were found between CCA-IMT, ANCA status, other clinical features and therapeutic regimens. Notably, the prevalence of traditional cardiovascular risk factors was comparable in patients with vs without an increased CCA-IMT. Conclusion: Ultrasound markers of subclinical atherosclerosis are increased in EGPA patients as compared with controls, independently of traditional cardiovascular risk factors.
MeSH term(s)	Humans ; Carotid Intima-Media Thickness ; Granulomatosis with Polyangiitis/complications ; Granulomatosis with Polyangiitis/diagnostic imaging ; Churg-Strauss Syndrome ; Risk Factors ; Atherosclerosis/diagnostic imaging ; Atherosclerosis/etiology ; Plaque, Atherosclerotic
Language	English
Publishing date	2022-07-18
Publishing country	England
Document type	Journal Article
ZDB-ID	1464822-2
ISSN	1462-0332 ; 1462-0324
ISSN (online)	1462-0332
ISSN	1462-0324
DOI	10.1093/rheumatology/keac427
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Article ; Online: SARS-CoV-2 infection among patients with systemic autoimmune diseases.

Emmi, Giacomo / Bettiol, Alessandra / Mattioli, Irene / Silvestri, Elena / Di Scala, Gerardo / Urban, Maria Letizia / Vaglio, Augusto / Prisco, Domenico

Autoimmunity reviews

2020 Volume 19, Issue 7, Page(s) 102575

Abstract: Objectives: This study aimed to evaluate the prevalence of clinically overt SARS-CoV-2 infection (COVID-19) among patients with systemic autoimmune diseases residing in Tuscany, and to compare it with that observed in the general Tuscan population.: ... ...

Abstract	Objectives: This study aimed to evaluate the prevalence of clinically overt SARS-CoV-2 infection (COVID-19) among patients with systemic autoimmune diseases residing in Tuscany, and to compare it with that observed in the general Tuscan population. Methods: In this cross-sectional study, Tuscan outpatients with systemic autoimmune diseases followed at a tertiary referral centre were telephonically interviewed between April 1st-14th 2020 to collect demographic and clinical data, information on ongoing immunomodulating/immunosuppressive treatments, and on the presence of symptoms suspected of SARS-CoV-2 or of a confirmed infection. Results: 458 patients were interviewed [74% female, median age 56 years (IQR 43-68)]; 56% of them were receiving corticosteroids, 44% traditional disease-modifying anti-rheumatic drugs (DMARDs), of whom 23% hydroxychloroquine, 5% colchicine, while 41% were on biologic DMARDs (of whom 9% on tocilizumab). Thirteen patients reported symptoms suggesting SARS-CoV-2 infection. Of them, 7 had undergone nasopharyngeal swab and only one was positive and developed severe SARS-CoV-2 complications. Within our cohort, the prevalence of SARS-CoV-2 infection was therefore 0.22% (0.01-1.21%), comparable to that observed in the general population of Tuscany [0.20% (0.20-0.21%), p = .597]. Conclusions: Patients with systemic autoimmune diseases do not seem to carry an increased risk of SARS- CoV-2 infection as compared to the general population.
MeSH term(s)	Adrenal Cortex Hormones/therapeutic use ; Adult ; Aged ; Antibodies, Monoclonal, Humanized/therapeutic use ; Antirheumatic Agents/therapeutic use ; Autoimmune Diseases/complications ; Autoimmune Diseases/drug therapy ; Betacoronavirus ; COVID-19 ; Colchicine/therapeutic use ; Coronavirus Infections/complications ; Cross-Sectional Studies ; Female ; Humans ; Hydroxychloroquine/therapeutic use ; Italy ; Male ; Middle Aged ; Pandemics ; Pneumonia, Viral/complications ; SARS-CoV-2
Chemical Substances	Adrenal Cortex Hormones ; Antibodies, Monoclonal, Humanized ; Antirheumatic Agents ; Hydroxychloroquine (4QWG6N8QKH) ; tocilizumab (I031V2H011) ; Colchicine (SML2Y3J35T)
Keywords	covid19
Language	English
Publishing date	2020-05-05
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	2144145-5
ISSN	1873-0183 ; 1568-9972
ISSN (online)	1873-0183
ISSN	1568-9972
DOI	10.1016/j.autrev.2020.102575
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Article ; Online: A unique circulating miRNA profile highlights thrombo-inflammation in Behçet's syndrome.

Emmi, Giacomo / Bagni, Giacomo / Lastraioli, Elena / Di Patti, Francesca / Bettiol, Alessandra / Fiorillo, Claudia / Becatti, Matteo / Silvestri, Elena / Urban, Maria Letizia / Emmi, Lorenzo / Prisco, Domenico / Arcangeli, Annarosa

Annals of the rheumatic diseases

2021 Volume 81, Issue 3, Page(s) 386–397

Abstract: Objectives: Behçet's syndrome (BS) is a rare systemic vasculitis often complicated by thrombotic events. Given the lack of validated biomarkers, BS diagnosis relies on clinical criteria.In search of novel biomarkers for BS diagnosis, we determined the ... ...

Abstract	Objectives: Behçet's syndrome (BS) is a rare systemic vasculitis often complicated by thrombotic events. Given the lack of validated biomarkers, BS diagnosis relies on clinical criteria.In search of novel biomarkers for BS diagnosis, we determined the profile of plasmatic circulating microRNAs (ci-miRNAs) in patients with BS compared with healthy controls (HCs). Methods: ci-miRNA profile was evaluated by microarray in a screening cohort (16 patients with BS and 18 HCs) and then validated by poly(T) adaptor PCR (PTA-PCR) in a validation cohort (30 patients with BS and 30 HCs). Two disease control groups (30 patients with systemic lupus erythematosus (SLE) and 30 patients with giant cell arteritis (GCA) were also analysed. Results: From the microarray screening, 29 deregulated (differentially expressed (DE)) human ci-miRNAs emerged. A hierarchical cluster analysis indicated that DE ci-miRNAs clearly segregated patients from controls, independently of clinical features. PTA-PCR analysis on the validation cohort confirmed the deregulation of miR-224-5p, miR-206 and miR-653-5p. The combined receiver operating characteristic (ROC) curve analyses showed that such ci-miRNAs discriminate BS from HCs (and BS with active vs inactive disease), as well as BS from patients with SLE and GCA.The functional annotation analyses (FAAs) showed that the most enriched pathways affected by DE ci-miRNAs (ie, cell-matrix interaction, oxidative stress and blood coagulation) are related to thrombo-inflammatory mechanisms. Accordingly, the expression of the three ci-miRNAs from the validation cohort significantly correlated with leucocyte reactive oxygen species production and plasma lipid peroxidation. Conclusions: The ci-miRNA profile identified in this study may represent a novel, poorly invasive BS biomarker, while suggesting an epigenetic control of BS-related thrombo-inflammation.
MeSH term(s)	Adult ; Behcet Syndrome/blood ; Behcet Syndrome/genetics ; Biomarkers/blood ; Case-Control Studies ; Circulating MicroRNA/blood ; Female ; Gene Expression Profiling ; Giant Cell Arteritis/blood ; Giant Cell Arteritis/genetics ; Humans ; Lupus Erythematosus, Systemic/blood ; Lupus Erythematosus, Systemic/genetics ; Male ; MicroRNAs/blood ; Polymerase Chain Reaction ; Prospective Studies ; ROC Curve ; Thromboinflammation/blood ; Thromboinflammation/genetics
Chemical Substances	Biomarkers ; Circulating MicroRNA ; MIRN206 microRNA, human ; MIRN224 microRNA, human ; MIRN653 microRNA, human ; MicroRNAs
Language	English
Publishing date	2021-11-29
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	7090-7
ISSN	1468-2060 ; 0003-4967
ISSN (online)	1468-2060
ISSN	0003-4967
DOI	10.1136/annrheumdis-2021-220859
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Article: Prevalence and clinical course of SARS-CoV-2 infection in patients with Behçet's syndrome.

Mattioli, Irene / Bettiol, Alessandra / Silvestri, Elena / Urban, Maria Letizia / Palermo, Adalgisa / Fagni, Filippo / Malandrino, Danilo / Del Bianco, Alessandra / Prisco, Domenico / Emmi, Giacomo

Clinical and experimental rheumatology

2021 Volume 39 Suppl 132, Issue 5, Page(s) 47–50

Abstract: Objectives: We aimed to assess the prevalence of SARS-CoV-2 infection among Behçet's syndrome (BS) patients, evaluating the possible association between demographic and clinical features and the risk of infection. Moreover, we aimed to evaluate the ... ...

Abstract	Objectives: We aimed to assess the prevalence of SARS-CoV-2 infection among Behçet's syndrome (BS) patients, evaluating the possible association between demographic and clinical features and the risk of infection. Moreover, we aimed to evaluate the possible association between BS disease activity and treatment, and the risk of SARS-CoV-2 infection. Methods: A survey was conducted on BS patients followed at the Behçet's Centre of the Careggi University Hospital, Florence, Italy. We further evaluated the possible association between BS disease activity and treatment, and the risk of SARS-CoV-2 infection. Results: Out of 335 BS patients contacted, fourteen cases of SARS-CoV-2 were identified between April 1st, 2020 and February 9th, 2021, suggesting a prevalence of SARS-CoV-2 infection among BS patients of 4.2%, in line with the data of the general population in Italy (4.4%). When comparing clinical features between SARS-CoV-2 cases and matched SARS-CoV-2 negative BS patients, we found that the presence of different disease manifestations did not significantly differ between the two groups. SARS-CoV-2 cases and controls were also comparable in terms of immunosuppressive therapy, with the only exception of corticosteroids (71.4% vs. 35.7%, p=0.030), whose daily dose was significantly higher in cases than controls [5mg/day (IQR 0-10,) vs. 0 mg/day (IQR 0-5), p=0.005], suggesting that the right timing of usage and the more appropriate dosage of corticosteroid are a key question for the better management of these patients. Conclusions: Based on our results, patients with BS do not seem to be at a greater risk of SARS-CoV-2 infection or severe complications compared with the general population.
MeSH term(s)	Adrenal Cortex Hormones/therapeutic use ; Behcet Syndrome/diagnosis ; Behcet Syndrome/drug therapy ; Behcet Syndrome/epidemiology ; COVID-19 ; Humans ; Prevalence ; SARS-CoV-2
Chemical Substances	Adrenal Cortex Hormones
Language	English
Publishing date	2021-06-09
Publishing country	Italy
Document type	Journal Article
ZDB-ID	605886-3
ISSN	1593-098X ; 0392-856X
ISSN (online)	1593-098X
ISSN	0392-856X
DOI	10.55563/clinexprheumatol/pmnqmf
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Article ; Online: Complement blockade in ANCA-associated vasculitis: an index case, current concepts and future perspectives.

Manenti, Lucio / Urban, Maria Letizia / Maritati, Federica / Galetti, Maricla / Vaglio, Augusto

Internal and emergency medicine

2017 Volume 12, Issue 6, Page(s) 727–731

Abstract: Complement alternative pathway (cAP) hyperactivation seems to be involved in ANCA-associated vasculitis (AAV). We here describe a case of AAV with severe activation of cAP that developed acute renal failure. No mutation predisposing to cAP dysregulation ... ...

Abstract	Complement alternative pathway (cAP) hyperactivation seems to be involved in ANCA-associated vasculitis (AAV). We here describe a case of AAV with severe activation of cAP that developed acute renal failure. No mutation predisposing to cAP dysregulation was identified. We treated our patient with the standard immunosuppressive therapy, but disease progression was only reversed after the addition of eculizumab, a monoclonal antibody against C5; the patient eventually achieved an almost complete renal function recovery. A review of the available literature about the role of complement targeted therapies in the treatment of AAV is discussed.
MeSH term(s)	Aged ; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/drug therapy ; Antibodies, Monoclonal, Humanized/pharmacology ; Antibodies, Monoclonal, Humanized/therapeutic use ; Cyclophosphamide/pharmacology ; Cyclophosphamide/therapeutic use ; Disease Progression ; Female ; Glomerulonephritis/immunology ; Glucocorticoids/pharmacology ; Glucocorticoids/therapeutic use ; Humans ; Immunosuppressive Agents/pharmacology ; Immunosuppressive Agents/therapeutic use ; Methylprednisolone/pharmacology ; Methylprednisolone/therapeutic use ; Renal Insufficiency
Chemical Substances	Antibodies, Monoclonal, Humanized ; Glucocorticoids ; Immunosuppressive Agents ; Cyclophosphamide (8N3DW7272P) ; eculizumab (A3ULP0F556) ; Methylprednisolone (X4W7ZR7023)
Language	English
Publishing date	2017-02-13
Publishing country	Italy
Document type	Journal Article ; Review
ZDB-ID	2454173-4
ISSN	1970-9366 ; 1828-0447
ISSN (online)	1970-9366
ISSN	1828-0447
DOI	10.1007/s11739-017-1636-6
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