Publications by authors named "Daniela Melchiorre"

28 Publications

  • Page 1 of 1

THE ROLE OF CHEST CT IN DECIPHERING INTERSTITIAL LUNG INVOLVEMENT: SYSTEMIC SCLEROSIS VERSUS COVID-19.

Rheumatology (Oxford) 2021 Jul 28. Epub 2021 Jul 28.

Department of Experimental and Clinical Medicine, University of Florence, and Infectious and TropicalDiseases Unit, AOUC, Florence, Italy.

Objective: To identify the main computed tomography (CT) features that may help distinguishing a progression of interstitial lung disease (ILD) secondary to Systemic sclerosis (SSc) from COVID-19 pneumonia.

Methods: This multicentric study included 22 international readers divided in the radiologist group (RAD) and non-radiologist group (nRAD). A total of 99 patients, 52 with COVID-19 and 47 with SSc-ILD, were included in the study.

Results: Fibrosis inside focal ground glass opacities (GGO) in the upper lobes; fibrosis in the lower lobe GGO; reticulations in lower lobes (especially if bilateral and symmetrical or associated with signs of fibrosis) were the CT features most frequently associated with SSc-ILD. The CT features most frequently associated with COVID- 19 pneumonia were: consolidation (CONS) in the lower lobes, CONS with peripheral (both central/peripheral or patchy distributions), anterior and posterior CONS and rounded-shaped GGOs in the lower lobes. After multivariate analysis, the presence of CONS in the lower lobes (p < 0.0001) and signs of fibrosis in GGO in the lower lobes (p < 0.0001) remained independently associated with COVID-19 pneumonia or SSc-ILD, respectively. A predictive score was created which resulted positively associated with the COVID-19 diagnosis (96.1% sensitivity and 83.3% specificity).

Conclusion: The CT differential diagnosis between COVID-19 pneumonia and SSc-ILD is possible through the combination the proposed score and the radiologic expertise. The presence of consolidation in the lower lobes may suggest a COVID-19 pneumonia while the presence of fibrosis inside GGO may indicate a SSc-ILD.
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http://dx.doi.org/10.1093/rheumatology/keab615DOI Listing
July 2021

THE MUSCLE SHORTENING MANOEUVRE: APPLICABILITY AND PRELIMINARY EVALUATION IN CHILDREN WITH HEMIPLEGIC CEREBRAL PALSY: A RETROSPECTIVE ANALYSIS.

J Rehabil Med Clin Commun 2021 17;4:1000062. Epub 2021 Jun 17.

Functional Rehabilitation Activities, Azienda Unità Sanitaria Locale, Toscana Centro, Prato, Italy.

Introduction: Physiotherapy plays a key role in cerebral palsy rehabilitation, through addressing body function/structure deficits, minimizing activity limitations, and encouraging participation. The muscle shortening manoeuvre is an innovative therapeutic technique, characterized by the ability to induce changes in muscle strength in a short time.

Objective: To describe the applicability and estimate the effect of the muscle shortening manoeuvre applied to improve motor weakness and joint excursion of the ankle in children with hemiplegic cerebral palsy.

Methods: Nine children with hemiplegic cerebral palsy received 3 intervention sessions in one week. Muscle strength, passive and active range of motion were assessed before, during and after the training, and at 1-week follow-up.

Results: The children experienced an immediate increase in muscle strength and joint excursion of the ankle; the improvements were still present at follow-up after 7 days.

Conclusion: The muscle shortening manoeuvre may be an effective intervention to induce an immediate increase in muscle strength and range of motion of the ankle in children affected by hemiplegia due to cerebral palsy, thus promoting better physical functioning.
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http://dx.doi.org/10.2340/20030711-1000062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8259804PMC
June 2021

Oral Species in Systemic Sclerosis.

Microorganisms 2021 Jun 15;9(6). Epub 2021 Jun 15.

Department of Experimental and Clinical Medicine, Department of Geriatric Medicine, Division of Rheumatology, University of Firenze, 50124 Firenze, Italy.

In systemic sclerosis (SSc), the gastrointestinal tract (GIT) plays a central role in the patient's quality of life. The microbiome populates the GIT, where a relationship between the and gastrointestinal motility has been suggested. In this study, the analysis of oral species in SSc patients and healthy subjects using culture-independent molecular techniques, together with a review of the literature on microbiota and lactobacilli in SSc, has been carried out. Twenty-nine SSc female patients (mean age 62) and twenty-three female healthy subjects (HS, mean age 57.6) were enrolled and underwent tongue and gum swab sampling. Quantitative PCR was conducted in triplicate using specific primers 1, 1o and 2 for the RNA-polymerase β subunit gene. Our data show significantly ( = 0.0211) lower spp sequences on the tongue of patients with SSc compared to HS. The mean value of the amount of gene on the gumsofSSc patients was minor compared to HS. A significant difference between tongue and gums ( = 0.0421) was found in HS but not in SSc patients. In conclusion, our results show a lower presence of in the oral cavity of SSc patients. This strengthens the hypothesis that may have both a protective and therapeutic role in SSc patients.
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http://dx.doi.org/10.3390/microorganisms9061298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8232208PMC
June 2021

Rehabilitation of the face and temporomandibular joint in systemic sclerosis.

Ther Adv Musculoskelet Dis 2021 8;13:1759720X211020171. Epub 2021 Jun 8.

Researcher in Rheumatology, Department of Experimental and Clinical Medicine, Division of Rheumatology, University of Florence, Largo Brambilla 3, Florence, 50134, Italy.

Background: Systemic sclerosis (SSc) alterations of the face and of the mouth cause aesthetic modifications and disability, impairing self-esteem and quality of life (QoL). The aim of this study was to verify the effects of two rehabilitation protocols on facial mimic and mouth opening.

Methods: A total of 47 SSc patients (40 females and 7 males, mean age ± SD 59.08 ± 10.31 years), were consecutively selected: 22 were randomly assigned to protocol 1 [home exercises for temporomandibular joint (TMJ), mimic, masticatory and cervical spine muscles] and 25 to protocol 2 (home exercises and combined physiotherapeutic procedures performed by a physiotherapist). Each treatment had a duration of 12 weeks with a follow up of 8 weeks. TMJ dysfunction, orofacial involvement, disability, QoL, and safety were assessed at enrollment (T0), at the end of the treatment (T1), and at follow up (T2).

Results: Both Protocol 1 and Protocol 2 induced significant improvements of some clinical and clinimetric parameters, but better results were obtained with Protocol 2. In the comparison between the effects of Protocol 1 and Protocol 2 at T1 and T2, a significant difference was observed only for Mouth Handicap in SSc [MHISS; Total ( = 0.00178] and for MHISS Mouth opening ( = 0.0098) at T1. No significant difference of indices of short-form 36 was observed.

Conclusion: The present data suggest that TMJ involvement in SSc may be managed by rehabilitation treatments. The action of a physiotherapist prescribing and personalizing exercises may induce better therapeutic effects.
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http://dx.doi.org/10.1177/1759720X211020171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8191075PMC
June 2021

When should a rare inherited connective tissue disorder be suspected in bicuspid aortic valve by primary-care internists and cardiologists? Proposal of a score.

Intern Emerg Med 2021 Apr 19;16(3):609-615. Epub 2020 Sep 19.

Cardiology Service, CMSR Veneto Medica, Altavilla Vicentina, Italy.

Size threshold for aortic surgery in bicuspid aortic valve (BAV) is debated. Connective tissue disorders (CTDs) are claimed as a clinical turning point, suggesting early surgery in BAV patients with CTD. Thus, we aimed at developing a score to detect high risk of carrying CTDs in consecutive BAVs from primary care. Ninety-eight BAVs without ectopia lentis or personal/family history of aortic dissection were studied at the Marfan syndrome Tuscany Referral Center. Findings were compared with those detected in 84 Marfan patients matched for sex and age. We selected traits with high statistical difference between MFS and BAV easily obtainable by cardiologists and primary-care internists: mitral valve prolapse, myopia ≥ 3DO, pectus carenatum, pes planus, wrist and thumb signs, and difference between aortic size at root and ascending aorta ≥ 4 mm. Clustering of ≥ 3 of these manifestations were more frequent in Marfan patients than in BAVs (71.4% vs 6.1%, p < 0.0001) resulting into an Odds Ratio to be affected by MFS of 38.3 (95% confidence intervals 14.8-99.3, p < 0.0001). We propose a score assembling simple clinical and echocardiographic variables resulting in an appropriate referral pattern of BAVs from a primary-care setting to a tertiary center to evaluate the presence of a potential, major CTD.
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http://dx.doi.org/10.1007/s11739-020-02458-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049921PMC
April 2021

Low bone mass and hypovitaminosis D in haemophilia: A single-centre study in patients with severe and moderate haemophilia A and B.

Haemophilia 2020 Sep 25;26(5):898-906. Epub 2020 Aug 25.

Center for Bleeding Disorders and Coagulation, Careggi University Hospital, Firenze, Italy.

Introduction: Haemophilia (H) is frequently associated with a multifactorial reduction in bone mineral density (BDM), but little is known about possible differences between HA and HB according to their severity.

Aim: To evaluate the association between low bone mineral density (BMD), 25-hydroxyvitamin D [25(OH)D] concentrations and bone turnover markers in patients with HA and HB younger or older than 50 years.

Methods: In 78 patients <50 years and 33 patients >50 years with severe (S) or moderate (M) HA and HB, BMD was measured by dual-energy X-ray absorptiometry at femoral neck (FN) and lumbar spine and then correlated to annual bleeding rate (ABR), World Federation of Haemophilia orthopaedic joint scale (WFH score), 25(OH)D concentrations, parathyroid hormone (PTH), amino-terminal telopeptide of type 1 collagen (NTx), urinary pyridinolines, osteocalcin and bone-specific alkaline phosphatase.

Results: Overall, a high prevalence of hypovitaminosis D was diagnosed. In patients <50 years, low FN-BMD was significantly more frequent in HA than in HB, while PTH, pyridinolines, ABR and WFH score were associated with H type and severity. In patients >50 years, similarly low FN-BMD was observed in HA and HB, while ABR and WFH score were associated with H type and severity, being milder in HB.

Conclusions: Low bone mass is a frequent comorbidity in haemophilic patients of all ages, apart from those with MHB. Clinical and laboratory assessments confirm a higher bone impairment and faster bone resorption in HA compared with HB. Looking at H type and severity, MHB seems to have a normal bone metabolism and a less severe disease.
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http://dx.doi.org/10.1111/hae.14127DOI Listing
September 2020

Effect of Dysmetabolisms and Comorbidities on the Efficacy and Safety of Biological Therapy in Chronic Inflammatory Joint Diseases.

J Clin Med 2020 May 2;9(5). Epub 2020 May 2.

Division of Rheumatology, Department of Experimental and Clinical Medicine, University of Florence, Via delle Oblate 4, 50141 Florence, Italy.

In the present study we evaluated how systemic arterial hypertension (SAH), dyslipidemia and diabetes mellitus influence the efficacy, safety and retention rate of biological disease-modifying anti-rheumatic drug (bDMARD) treatment in rheumatic musculoskeletal disorders (RMDs). The charts of RMD patients treated with the first-line bDMARD were reviewed, collecting data on safety, efficacy and comorbidities at prescription (baseline, BL), after 6 months (6M) and at last observation on bDMARD (last observation time, LoT). In 383 RMD patients, a higher rate of adverse events at 6M ( = 0.0402) and at LoT ( = 0.0462) was present in dyslipidemic patients. Patients who developed dyslipidemia or SAH during bDMARD treatment had similar results (dyslipidemia = 0.0007; SAH = 0.0319) with a longer bDMARD retention as well (dyslipidemia < 0.0001; SAH < 0.0001). SAH patients on angiotensin converting enzyme inhibitors (ACEis) or angiotensin-II receptor blockers (ARBs) continued bDMARDs for longer than non-exposed patients ( = 0.001), with higher frequency of drug interruption for long-standing remission rather than inefficacy or adverse reactions ( = 0.0258). Similarly, dyslipidemic patients on statins had a better bDMARD retention than not-exposed patients ( = 0.0420). In conclusion, SAH and dyslipidemia may be associated with higher frequency of adverse events but a better drug retention of first-line bDMARD in RMDs, suggesting an additional effect of ACEis/ARBs or statins on the inflammatory process and supporting their use in RMD bDMARD patients with SAH/dyslipidemia.
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http://dx.doi.org/10.3390/jcm9051310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7290363PMC
May 2020

The Renal Resistive Index: A New Biomarker for the Follow-up of Vascular Modifications in Systemic Sclerosis.

J Rheumatol 2021 02 1;48(2):241-246. Epub 2020 Apr 1.

C. Bruni, MD, G. Lepri, MD, G. Tesei, MD, S. Guiducci, MD, D. Melchiorre, MD, S. Bellando-Randone, MD, M. Matucci-Cerinic, MD, Department of Experimental and Clinical Medicine, University of Florence, and Division of Rheumatology AOUC & Scleroderma Unit, Florence.

Objective: The aim of the present retrospective observational study was to evaluate the change of Renal Resistive Index (RRI) over time (ΔRRI) and under treatment in patients with systemic sclerosis (SSc) as well as to correlate these changes with disease complications.

Methods: Two hundred thirty patients [29 male, median age 57 (IQR 48-67) yrs] were enrolled. At baseline and follow-up (3.43, IQR 2.81-4.45 yrs), we collected the following data: disease variables, nailfold videocapillaroscopy (NVC) pattern, forced vital capacity (FVC), diffusing lung capacity for carbon monoxide (DLCO), systolic pulmonary arterial pressure (sPAP), presence of interstitial lung disease, RRI, evaluation of glomerular filtration rate, and new onset of pulmonary arterial hypertension (PAH).

Results: RRI value is high in SSc patients with digital ulcers and anticentromere antibodies, active and late NVC patterns, and limited cutaneous SSc. A significant correlation was observed between ΔRRI and ΔsPAP (R = 0.17, = 0.02), with statistically higher ΔRRI (0.08 ± 0.02 vs 0.03 ± 0.05, = 0.04) in patients complicated by PAH onset. No other new-onset complication was associated with ΔRRI. The receiver-operating characteristic curve analysis confirmed the predictive role of ΔRRI in development of new PAH (area under the curve 0.84, 95% CI 0.75-0.93, = 0.02). In patients with SSc never exposed to sildenafil, ΔRRI was higher (0.04 ± 0.05) compared to both patients exposed to sildenafil during the study period (0.01 ± 0.05, = 0.03) or in those exposed at the time of baseline evaluation (0.00 ± 0.05, = 0.01).

Conclusion: RRI and its variation in time are a reliable marker of SSc-related vasculopathy, both in renal and extrarenal compartments.
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http://dx.doi.org/10.3899/jrheum.191101DOI Listing
February 2021

Enthesopathy and involvement of synovio-entheseal complex in systemic sclerosis: an ultrasound pilot study.

Rheumatology (Oxford) 2020 03;59(3):580-585

Department of Experimental and Clinical Medicine, Section of Internal Medicine, University of Florence, and Division of Rheumatology, Azienda Ospedaliero-Universitaria Careggi (AOUC), Florence, Italy.

Objectives: SSc is a chronic autoimmune disease characterized by inflammation of the skin and multiple internal organs. Articular involvement is one of the main features of SSc, and typical hallmarks of SpA have been found in SSc patients. The aim of the present study was to estimate the prevalence of entheseal and synovio-entheseal complex (SEC) alterations in a cohort of SSc patients.

Methods: One hundred SSc patients and 25 healthy subjects were included in this cross-sectional study. The enthesis sites of lateral epicondylar common extensor tendons (CET) and the enthesis of the Glasgow Ultrasound Enthesis Scoring System were evaluated. SEC involvement was evaluated only at CET enthesis.

Results: In SSc, the Glasgow Ultrasound Enthesis Scoring System score was significantly higher (median 4.0, interquartile range 2.0-7.0) than in controls (median 1.0, interquartile range 0.0-3.0) (P < 0.0001). CET enthesis of SSc patients showed more frequent US B-mode alterations than that of controls (χ2 = 11.47, P = 0.0007 for size; χ2 = 13.79, P = 0.0002 for cortical irregularity, χ2 = 5.24, P = 0.022 for calcification/enthesophytes). Power Doppler US signal at CET enthesis was significantly more frequent in SSc patients than in healthy controls (χ2 = 9.11, P = 0.0025), as was the concomitant SEC involvement (χ2 = 8.52, P = 0.0035).

Conclusion: These data show that SSc patients frequently present US features of enthesopathy. Moreover, CET enthesopathy was correlated with SEC inflammation, suggesting that entheseal inflammation in SSc may share the same micro-anatomical targets as found in SpA.
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http://dx.doi.org/10.1093/rheumatology/kez322DOI Listing
March 2020

TNF-α/TNF-R System May Represent a Crucial Mediator of Proliferative Synovitis in Hemophilia A.

J Clin Med 2019 Jun 28;8(7). Epub 2019 Jun 28.

Department of Experimental and Clinical Medicine, Section of Rheumatology, University of Florence, 50134 Florence, Italy.

Hemophilic arthropathy (HA) typically begins with proliferative synovitis that shares some similarities with inflammatory arthritides, in which the proinflammatory cytokine tumor necrosis factor (TNF)-α has a crucial pathogenetic role. Inappropriate release of TNF-α was shown to contribute to arthropathy development following intra-articular bleeding in hemophilic mice. Here, we were interested in determining whether systemic levels of TNF-α and synovial tissue expression of the TNF-α/TNF receptor (TNF-R) system could be increased and related to joint damage in hemophilia A patients with severe HA. Serum levels of TNF-α measured by quantitative enzyme-linked immunosorbent assay (ELISA) were significantly increased in HA patients ( = 67) compared to healthy controls (n = 20). In HA patients, elevated TNF-α levels were significantly associated with the number of hemarthroses, the grade of synovial hypertrophy, and both the clinical World Federation of Hemophilia score and ultrasound score. The expression of TNF-α, TNF-R1, and TNF-R2 was strongly increased in HA synovium (n = 10) compared to the non-inflamed osteoarthritis control synovium (n = 8), as assessed by both immunohistochemistry and Western blotting. Increased protein levels of TNF-α, TNF-R1, and TNF-R2 were retained in vitro by HA fibroblast-like synoviocytes (n = 6) with respect to osteoarthritis control fibroblast-like synoviocytes (n = 6). Stimulation with TNF-α resulted in a significant increase in HA fibroblast-like synoviocyte proliferation quantified by the water-soluble tetrazolium (WST)-1 assay, while it had no relevant effect on osteoarthritis fibroblast-like synoviocytes. Quantification of active/cleaved caspase-3 by ELISA demonstrated that TNF-α did not induce apoptosis either in HA or in osteoarthritis fibroblast-like synoviocytes. The TNF-α/TNF-R system may represent a crucial mediator of proliferative synovitis and, therefore, a new attractive target for the prevention and treatment of joint damage in HA patients. Our findings provide the groundwork for further clinical investigation of anti-TNF-α therapeutic feasibility in hemophiliacs.
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http://dx.doi.org/10.3390/jcm8070939DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678637PMC
June 2019

Targeting anticoagulant protein S to improve hemostasis in hemophilia.

Blood 2018 03 9;131(12):1360-1371. Epub 2018 Jan 9.

Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, and.

Improved treatments are needed for hemophilia A and B, bleeding disorders affecting 400 000 people worldwide. We investigated whether targeting protein S could promote hemostasis in hemophilia by rebalancing coagulation. Protein S (PS) is an anticoagulant acting as cofactor for activated protein C and tissue factor pathway inhibitor (TFPI). This dual role makes PS a key regulator of thrombin generation. Here, we report that targeting PS rebalances coagulation in hemophilia. PS gene targeting in hemophilic mice protected them against bleeding, especially when intra-articular. Mechanistically, these mice displayed increased thrombin generation, resistance to activated protein C and TFPI, and improved fibrin network. Blocking PS in plasma of hemophilia patients normalized in vitro thrombin generation. Both PS and TFPIα were detected in hemophilic mice joints. PS and TFPI expression was stronger in the joints of hemophilia A patients than in those of hemophilia B patients when receiving on-demand therapy, for example, during a bleeding episode. In contrast, PS and TFPI expression was decreased in hemophilia A patients receiving prophylaxis with coagulation factor concentrates, comparable to osteoarthritis patients. These results establish PS inhibition as both controller of coagulation and potential therapeutic target in hemophilia. The murine PS silencing RNA approach that we successfully used in hemophilic mice might constitute a new therapeutic concept for hemophilic patients.
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http://dx.doi.org/10.1182/blood-2017-09-800326DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5865230PMC
March 2018

Pathophysiology of Hemophilic Arthropathy.

J Clin Med 2017 Jun 25;6(7). Epub 2017 Jun 25.

Section of Internal Medicine, Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy.

Spontaneous joint bleeding and repeated hemarthroses lead to hemophilic arthropathy-a debilitating disease with a significant negative impact on mobility and quality of life. Iron, cytokines, and angiogenic growth factors play a pivotal role in the onset of the inflammatory process that involves the synovial tissue, articular cartilage, and subchondral bone, with early damages and molecular changes determining the perpetuation of a chronic inflammatory condition. Synovitis is one of the earliest complications of hemarthrosis, and is characterized by synovial hypertrophy, migration of inflammatory cells, and a high degree of neo-angiogenesis with subsequent bleeding. The pathogenic mechanisms and molecular pathways by which blood in the joint cavity causes articular cartilage and subchondral bone destruction have yet to be fully elucidated. Both cytokines and matrix metalloproteinases and hydroxyl radicals may induce chondrocyte apoptosis. Members of the tumor necrosis factor receptor superfamily (such as the molecular triad: osteoprotegerin-OPG; receptor activator of nuclear factor κB-RANK; RANK ligand-RANKL) seem instead to play a major role in the inflammatory process. These pathogenic processes interact with each other and ultimately lead to a fibrotic joint and the disabling condition characteristic of hemophilic arthropathy.
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http://dx.doi.org/10.3390/jcm6070063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5532571PMC
June 2017

Sonographic visibility of the sinus tarsi with a 12 MHz transducer.

J Ultrasound 2016 13;19(2):107-13. Epub 2014 Dec 13.

U.O. Chirurgia Generale e d'Urgenza, A.O.U.P., Ospedale Cisanello Pisa, Pisa, Italy ; Scuola SIUMB di Ecografia di Base e Specialistica in Urgenza ed Emergenza di Pisa, Pisa, Italy.

Objectives: To assess the value of ultrasonography in studies of the ligaments within the sinus tarsi (ST) in healthy subjects.

Materials And Methods: We examined 20 healthy volunteers using a 12-MHz transducer with THI and compound imaging. With the foot in inversion, the following structures were examined with coronal and transverse scans: (1) the root of the inferior extensor retinaculum (RIER); (2) the interosseous talocalcaneal ligament (ITCL); (3) the cervical ligament (CL); (4) the bifurcate ligament (BL); (5) the synovial recesses, which were examined for possible distention (distended synovial recesses, DSR). The sonographic features, orientation, and thickness of each ligament were assessed.

Results: The easiest structure to identify (visualized in 20/20 subjects) was the RIER, which formed a semiarch. The two deeper layers were hypoechoic, the superficial layer hyperechoic. The ITCL was situated posteriorly and deep with an oblique course. It appeared hypoechoic with a mean thickness of 4.06 mm ± 0.7. It was visualized in 18/20 (90 %) subjects. The CL (isoechoic/hyperechoic) was located more anteriorly at an intermediate depth. The orientation was almost vertical. It was visualized in 17/20 (85 %) subjects, with a mean thickness of 2.28 mm ± 0.34. The BL appeared hypoechoic. It was visualized in 19/20 (95 %) subjects with transverse (anterior end of the ST) and longitudinal scans. The calcaneonavicular and calcaneocuboid components displayed mean (SD) thicknesses of 2.09 mm ± 0.37 and 2.7 mm ± 0.32, respectively. The ITCL and RIER were visualized in the same scan as a semiarch. DSR was observed in 4/20 (20 %) subjects.

Conclusions: The present study shows that, in patients with suspected ST pathology, the anatomic structures that make up this recess can be adequately examined with ultrasonography performed with ordinary 12-MHz transducers.
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http://dx.doi.org/10.1007/s40477-014-0145-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4879007PMC
July 2016

A group of patients with Marfan's syndrome, who have finger and toe contractures, displays tendons' alterations upon an ultrasound examination: are these features common among classical Marfan patients?

Intern Emerg Med 2016 Aug 22;11(5):703-11. Epub 2016 Feb 22.

Department of Heart and Vessels, Regional Marfan Syndrome and Related Disorders Center, Careggi Hospital, Florence, Italy.

The involvement of the musculoskeletal system with other mild pleiotropic manifestations represents a clinical criterion, called "systemic features," to d iagnose Marfan's syndrome. We aimed to investigate the features of the hands and feet redressable contractures present in a group of Marfan patients. In 13 patients with previously diagnosed Marfan's syndrome, an accurate clinical examination was performed. In particular the characterization of the musculoskeletal system by visual analogic scale to measure muscle pain (VAS) and muscle strength (MRC system) was carried out; the Beighton scale score was used to evaluate the articular hypermobility. Ultrasound examination (US) was performed to detect deep-superficial flexor tendons and extensor tendons of both hands, and the short and long flexor and extensor tendons of the fingers and toes in static and dynamic positions. The ImageJ program was adopted to measure a profile of tendon echo-intensity. A reduction of the thickness of all tendons was detected by US in our patients; the VAS and Beighton scale scores were in normal ranges. The profile of tendon echo-intensity showed different textural details in all Marfan patients. This study provides evidence for other contractures' localization, and for altered findings of the tendons in patients with Marfan syndrome and finger/toe contractures. These changes may be associated with structural modifications in connective tissue.
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http://dx.doi.org/10.1007/s11739-016-1399-5DOI Listing
August 2016

Gait abnormalities in early rheumatoid arthritis with temporomandibular joint involvement.

Clin Exp Rheumatol 2016 May-Jun;34(3):561. Epub 2016 Feb 9.

Unit of Rheumatology, Department of Experimental and Clinical Medicine, University of Florence, Italy.

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August 2016

Clinical, instrumental, serological and histological findings suggest that hemophilia B may be less severe than hemophilia A.

Haematologica 2016 Feb 22;101(2):219-25. Epub 2015 Oct 22.

Center for Bleeding Disorders, Careggi University Hospital, Florence, Italy.

Recent evidence suggests that patients with severe hemophilia B may have a less severe disease compared to severe hemophilia A. To investigate clinical, radiological, laboratory and histological differences in the arthropathy of severe hemophilia A and hemophilia B, 70 patients with hemophilia A and 35 with hemophilia B with at least one joint bleeding were consecutively enrolled. Joint bleedings (<10, 10-50, >50), regimen of treatment (prophylaxis/on demand), World Federation of Hemophilia, Pettersson and ultrasound scores, serum soluble RANK ligand and osteoprotegerin were assessed in all patients. RANK, RANK ligand and osteoprotegerin expression was evaluated in synovial tissue from 18 hemophilia A and 4 hemophilia B patients. The percentage of patients with either 10-50 or more than 50 hemarthrosis was greater in hemophilia A than in hemophilia B (P<0.001 and P=0.03, respectively), while that with less than 10 hemarthrosis was higher in hemophilia B (P<0.0001). World Federation of Hemophilia (36.6 vs. 20.2; P<0.0001) and ultrasound (10.9 vs. 4.3; P<0.0001) score mean values were significantly higher in hemophilia A patients. Serum osteoprotegerin and soluble RANK ligand were decreased in hemophilia A versus hemophilia B (P<0.0001 and P=0.006, respectively). Osteoprotegerin expression was markedly reduced in synovial tissue from hemophilia A patients. In conclusion, the reduced number of hemarthrosis, the lower World Federation of Hemophilia and ultrasound scores, and higher osteoprotegerin expression in serum and synovial tissue in hemophilia B suggest that hemophilia B is a less severe disease than hemophilia A. Osteoprotegerin reduction seems to play a pivotal role in the progression of arthropathy in hemophilia A.
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http://dx.doi.org/10.3324/haematol.2015.133462DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4938330PMC
February 2016

Rheumatoid arthritis.

Autoimmune Dis 2013 28;2013:958437. Epub 2013 Nov 28.

Infectious Diseases Unit, University of Bologna, Bologna, Italy.

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http://dx.doi.org/10.1155/2013/958437DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3863497PMC
December 2013

Angiogenesis is increased in advanced haemophilic joint disease and characterised by normal pericyte coverage.

Eur J Haematol 2014 Mar 25;92(3):256-62. Epub 2013 Nov 25.

Coagulation Unit, Haematology Centre, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden; Department of Haematology and Coagulation, Skåne University Hospital, Malmö, Sweden.

Background: Repeated intra-articular bleedings in patients with haemophilia results in a crippling arthropathy for which no specific treatment is currently available. Recent studies have shown that neoangiogenesis is involved in the pathologic process. The aim of this study was to determine whether angiogenesis is dysregulated in haemophilic joint disease (HJD).

Methods: Synovial tissue and synovial fluid were collected from patients with severe haemophilia undergoing knee or hip replacement and from a control group consisting of non-haemophilic patients undergoing diagnostic procedures. In a second set of patients, blood samples were collected in patients with mild, moderate and severe haemophilia A when free from current bleeding. Analysis of microvascular density, vascular endothelial growth factor (VEGF) expression and pericyte coverage was performed by immunofluorescence. Analyses of VEGF concentrations in plasma, platelet lysates and synovial fluid were performed by ELISA.

Results: Microvascular density and VEGF expression were significantly increased in synovial tissue from haemophilic patients compared with controls (P = 0.005 and P = 0.02, respectively). There was no difference in pericyte coverage of synovial vessels or levels of VEGF in plasma, platelet lysates or synovial fluid.

Conclusions: Angiogenesis observed as synovial microvascular density, and VEGF expression is increased in HJD. As pericyte coverage was similar in synovial vessels from haemophilic and non-haemophilic patients, we assume that the vessels were mature, suggesting that the rate of new vessel formation is low in the chronic phase of haemophilic joint disease.
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http://dx.doi.org/10.1111/ejh.12227DOI Listing
March 2014

Anti-TNF-α therapy prevents the recurrence of joint bleeding in haemophilia and arthritis.

Rheumatology (Oxford) 2014 Mar 17;53(3):576-8. Epub 2013 Oct 17.

Rheumatology, Villa Monna Tessa, Viale Pieraccini 18,50134 Florence, Italy.

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http://dx.doi.org/10.1093/rheumatology/ket280DOI Listing
March 2014

Muscle shortening manoeuvre reduces pain and functional impairment in shoulder impingement syndrome: clinical and ultrasonographic evidence.

Clin Exp Rheumatol 2014 Jan-Feb;32(1):5-10. Epub 2013 Sep 18.

Department of Medicine, Rheumatology Unit, University of Florence, Italy.

Objectives: To evaluate the short-term efficacy of muscle shortening manoeuvre (MSM), by inducing an increase in strength of the shoulder muscles, for the treatment of shoulder impingement syndrome (SIS).

Methods: Sixty subjects (mean age: 58.6 years) with SIS were assigned to one of 3 different treatment interventions: 1) MSM: a series of fast accelerations in the upward direction was applied to the upper limb that was also submitted to forces acting in the opposite direction (added mass); 2) traditional physiotherapeutic technique: scapulothoracic gliding; 3) simple traction: the added mass was applied to the limb without the series of fast accelerations. Pain intensity, Neer's impingement sign, range of motion and muscle strength were assessed. Ultrasound (US) examination was performed before, immediately after and 30 days after each treatment to study the width of the subacromial-subdeltoid bursa, long biceps tendon sheath and acromioclavicular joint. Impingement was evaluated by dynamic examination.

Results: After treatment with MSM, pain was significantly reduced (p<0.001), Neer's impingement sign was negative, range of motion and muscle strength were increased. US examination showed that the widths of the subacromial-subdeltoid bursa (p<0.001), long biceps tendon sheath (p<0.001) and acromioclavicular joint (p<0.001) were significantly reduced; impingement was no more detected. After 30 days, improvement in clinical and US findings was maintained. In the two control groups, no significant changes were observed after treatment.

Conclusions: Clinical and US findings demonstrate that MSM, by inducing an increase in muscle strength, is effective in the short-term treatment of SIS.
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October 2014

Clinical and radiological evaluation of sacroiliac joints compared with ultrasound examination in early spondyloarthritis.

Rheumatology (Oxford) 2013 Jul 26;52(7):1293-7. Epub 2013 Mar 26.

Department of Biomedicine, Denothe Centre, Division of Rheumatology AOUC, University of Florence, Florence, Italy.

Objective: To compare clinical and X-ray examinations with US findings of SI joints (SIJ) in early SpA patients.

Methods: Twenty-three early SpA patients, diagnosed according to Assessment of SpondyloArthritis international Society criteria, were investigated clinically [sacral sulcus tenderness, BASMI, BASFI, BASDAI, pain and fatigue visual analogue scale (VAS), morning stiffness and sleep disturbance], with SIJ X-rays (New York score) and with My Lab70 US 7-10 MHz US (Esaote, Genoa, Italy), evaluating the width of the SIJ capsule and posterior sacroiliac (PSL) and sacrotuberosus (STL) ligament thickness and comparing the results with 23 healthy controls.

Results: SIJ width [right 2.2 (0.6) and left 2.3 (0.7) in SpA vs 1.6 (0.1) and 1.7 (0.2) in healthy controls, respectively, expressed as mean (s.d.)] and STL thickness [right 3.9 (1.3) and left 3.4 (1.0) vs 1.8 (0.1) and 1.8 (0.1), respectively, expressed as mean (s.d.)] were higher in SpA patients than in controls (P < 0.001 and P < 0.05, respectively). PSL thickness was similar in patients and controls. Only STL thickness was higher when SIJ was tender at clinical examination (P < 0.01) and correlated with pain VAS (P < 0.001) and BASFI (P < 0.05). Furthermore, SIJ US results were unrelated to X-ray findings (similar when X-ray sacroiliitis was present and not).

Conclusion: Our exploratory study suggested that in early SpA patients US might be a promising method, complementary to other imaging techniques, to study articular and soft tissue periarticular involvement of SIJ, independent of clinical and X-ray examination.
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http://dx.doi.org/10.1093/rheumatology/ket105DOI Listing
July 2013

RANK-RANKL-OPG in hemophilic arthropathy: from clinical and imaging diagnosis to histopathology.

J Rheumatol 2012 Aug 1;39(8):1678-86. Epub 2012 Jul 1.

Department of Anatomy, Histology and Forensic Medicine, University of Florence, Florence, Italy.

Objective: Hemarthrosis triggers hemophilic arthropathy, involving the target joints. The histopathogenesis of blood-induced joint damage remains unclear. The triad of receptor activator of nuclear factor-κB (RANK), RANK ligand (RANKL), and osteoprotegerin (OPG; RANK-RANKL-OPG) controls bone turnover. Our aim was to evaluate RANK-RANKL-OPG expression in the synovium of hemophilic patients with severe arthropathy.

Methods: Synovial biopsies were obtained from 18 patients with hemophilic arthropathy and 16 with osteoarthritis (OA) who were undergoing total knee replacement and synovectomy. The severity of hemophilic arthropathy was evaluated according to ultrasonography score, the World Federation of Hemophilia (WFH) orthopedic joint scale, and the radiographic Pettersson score. RANK-RANKL-OPG expression was examined by immunohistochemistry and Western blotting. Serum levels of soluble RANKL (sRANKL) and OPG from an extended group of 67 patients with hemophilic arthropathy and 30 healthy controls were measured by ELISA.

Results: The mean ultrasonography, WFH orthopedic joint scale, and Pettersson scores in patients with hemophilic arthropathy indicated severe arthropathy. A decreased expression of OPG was found in hemophilic arthropathy synovium compared with patients with OA. RANK and RANKL immunopositivity was strong in the lining and sublining layers in hemophilic arthropathy synovial tissue. Western blotting confirmed the immunohistological findings. Serum levels of sRANKL and OPG in patients with hemophilia were lower than in healthy controls.

Conclusion: In hemophilic arthropathy, the synovium highly expressed RANK and RANKL, whereas OPG immunopositivity decreased, suggesting an osteoclastic activation. Low tissue expression of OPG paralleled the serum levels of this protein and the severity of hemophilic arthropathy assessed by ultrasonography, Pettersson, and WFH orthopedic joint scale scores.
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http://dx.doi.org/10.3899/jrheum.120370DOI Listing
August 2012

Identification of the clinical features distinguishing psoriatic arthritis and fibromyalgia.

J Rheumatol 2012 Apr 15;39(4):849-55. Epub 2012 Jan 15.

UOC Day Hospital of Rheumatology, Istituto Ortopedico Gaetano Pini, Piazza A. Ferrari 1, 20122 Milan, Italy.

Objective: To identify the clinical features that can help to distinguish between psoriatic arthritis (PsA) and fibromyalgia (FM).

Methods: Our cross-sectional study was carried out in 10 Italian rheumatology centers between January and September 2009, and enrolled all consecutive patients with PsA and FM who agreed to participate. Standard clinical and laboratory data for PsA and FM were collected from all patients. Records were made of somatic symptoms, response to nonsteroidal antiinflammatory drugs (NSAID), self-evaluated pain, general health, disability, and responses to the Fibromyalgia Impact Questionnaire. Data were statistically analyzed by univariate and multivariate analyses, and receiver-operating characteristic curves. The analysis concentrated on the clinical features shared by the 2 conditions.

Results: Two hundred sixty-six patients with PsA (mean age 51.7 yrs; disease duration 10.2 yrs) and 120 patients with FM (mean age 50.2 yrs; disease duration 5.6 yrs) were evaluated. Univariate analysis showed that patients with FM had higher mean tender point and enthesitis scores, more somatic symptoms, and responded less to NSAID. Multivariate analysis showed that the presence of ≥ 6 FM-associated symptoms and ≥ 8 tender points was the best predictor of FM.

Conclusion: The shared clinical features of PsA and FM that had the greatest discriminating power for FM were the number of FM-associated symptoms and tender point count.
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http://dx.doi.org/10.3899/jrheum.110893DOI Listing
April 2012

Ultrasonography of the temporomandibular joint: comparison of findings in patients with rheumatic diseases and temporomandibular disorders. A preliminary report.

Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2005 Oct;100(4):481-5

Department of Neuroscience, University of Pisa, Italy.

Objective: The objective of the study was to compare findings from ultrasonography (US) of the temporomandibular joint (TMJ) in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and temporomandibular disorders (TMD).

Study Design: US assessment of the temporomandibular joints was bilaterally performed in 68 patients (22 with RA, 11 with PsA, and 35 with TMD). All the TMJs were assessed for the presence of disc displacement, effusion, and changes of the condylar profile, and the prevalence of such abnormalities was compared across the 3 groups of patients. To confirm generalizability of results, US findings were also compared with those of magnetic resonance (MR), taken as the standard of reference.

Results: Prevalence of disc displacement and changes in condylar profile were similar between patients with rheumatic diseases and temporomandibular disorders, while effusion was significantly more present in TMJs of TMD patients. Sensitivity of US to detect TMJ abnormalities was acceptable, while specificity was low for condylar alterations.

Conclusions: Temporomandibular joint involvement in patients with rheumatic diseases seems to be similar to that described in subjects with temporomandibular disorders. Ultrasonography confirmed to be an accurate technique to detect disc displacement and effusion within the temporomandibular joint, but not to detect condylar abnormalities.
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http://dx.doi.org/10.1016/j.tripleo.2005.02.071DOI Listing
October 2005

Anti-cyclic citrullinated peptide antibodies are highly associated with severe bone lesions in rheumatoid arthritis anti-CCP and bone damage in RA.

Autoimmunity 2004 Sep-Nov;37(6-7):495-501

Department of Medical and Surgical Care, Rheumatology Unit, University of Florence, Italy.

In the present study we investigated the predictive value of anti-cyclic citrullinated peptide antibodies (anti-CCP) in early rheumatoid arthritis (RA) with respect to the bone damage. Fifty-four patients with early RA (onset <12 months), 35 classified as established RA (onset >12 months), 33 healthy donors and 76 non-RA autoimmune diseases, were enrolled. Anti-CCP and IgG, IgA, IgM rheumatoid factors (RFs) were determined at baseline. Disease activity score (DAS 28) was calculated at the entry. Bone involvement was evaluated by X-rays and sonography. The specificity of anti-CCP was 98.4%; significantly higher than those of the IgM- (86.0%), IgA- (86.0%) and IgG-RFs (66.2%), respectively. Anti-CCP were detected in 23/54 (42.6%) early RA patients and in 16/35 (45.7%) established RA patients. In the early RA group, 6/33 (18.2%) of the patients without bone lesions, 12/16 (75%) with juxta-articular osteoporosis (JO) and 5/5 with joint erosions (JE) resulted positive showing a significant difference between the groups without and with radiological damage. In the established RA group a significant difference being between the group without radiological damage and that with JE was found. Finally, in patients without radiological lesions, examined by ultrasound, anti-CCP antibodies were detected only in subjects with pathologic findings (31.25%). Data here reported confirm that the presence of anti-CCP are specific for diagnosis of RA, of recent onset also and they are potentially useful as prognostic index of bone involvement.
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http://dx.doi.org/10.1080/08916930400011965DOI Listing
May 2005

Two novel mutations at exon 8 of the Sequestosome 1 (SQSTM1) gene in an Italian series of patients affected by Paget's disease of bone (PDB).

J Bone Miner Res 2004 Jun 2;19(6):1013-7. Epub 2004 Feb 2.

Department of Internal Medicine, Azienda Ospedaliera Careggi, Florence, Italy.

Unlabelled: PDB is genetically heterogeneous. Mutations of the sequestosome1 gene have been reported in sporadic and familial forms of Paget's in patients of French Canadian and British descent. Mutational analyses in different ethnic groups are needed to accurately investigate hereditary diseases. We describe two novel mutations of sequestosome1 in 62 Italian sporadic patients, confirming the role of the encoded protein in this disorder.

Introduction: Paget's disease of bone (PDB) is a relatively common disease of bone metabolism reported to affect up to 3% of whites over 55 years of age. The disorder is genetically heterogeneous, and at present, there is scientific evidence that at least eight different human chromosomal loci are correlated with its pathogenesis. Mutations of the sequestosome1 (SQSTM1) gene were identified as responsible for most of the sporadic and familial forms of Paget in patients of French Canadian and British descent. Such mutations were located at exon 7 and 8 levels, encoding for the ubiquitin protein-binding domain (UBA) and representing a mutational hot spot area.

Materials And Methods: To verify the involvement of this gene in Italian subjects affected by PDB, we performed mutational analysis in 62 sporadic PDB cases.

Results: We described three different mutations at exon 8 level: P392L, already described in the French Canadian population and families predominantly of British descendent, and two novel mutations consisting of the amino acid substitutions M404V and G425R. No significant differences in the clinical history of PDB have been observed in patients with SQSTM1 mutations in respect to those without.

Conclusions: Even though our findings suggest a minor involvement of the SQSTM1 gene in the pathogenesis of sporadic Italian Paget's cases, the identification of different significant mutations within the SQSTM1 gene in unrelated, but clinically similar individuals, offers extremely convincing evidence for a causal relationship between this gene and PDB. Longitudinal studies are needed to assess the penetrance of genotype/phenotype correlations. Our findings confirm the evidence of a clustered mutation area at this level in this disorder.
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http://dx.doi.org/10.1359/JBMR.040203DOI Listing
June 2004
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