928 results on '"Frediani B."'
Search Results
352. The laboratory approach in the diagnosis of systemic autoinflammatory diseases | L'approccio laboratoristico nella diagnostica delle malattie autoinfiammatorie sistemiche
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Cantarini, L., Rigante, D., Brizi, M. G., Sebastiani, G. D., Orso Maria Lucherini, Galeazzi, M., and Frediani, B.
353. Perspective on the clinical practice management of hypovitaminosis D from a meeting of Italian experts
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Fassio, A., Bertoldo, F., Braga, V., Brandi, M. L., Calvieri, S., Cianferotti, L., Colao, A., D Amelio, P., D Avola, G. M., Esposti, L. D., Frediani, B., Giannini, S., Giusti, A., Gonnelli, S., Malavolta, N., Marcocci, C., Minisola, S., Napoli, N., Nuti, R., Passeri, G., Rossini, M., Sinigaglia, L., Viapiana, O., Francesco Vierucci, Gatti, D., Abdel Jaber, M., Benini, C., Boner, A., Bortolotti, R., Brigo, M., Catalano, A., Ferlin, A., Giollo, A., Girasole, G., Idolazzi, L., Lello, S., Maestri, E., Martinis, F., Muratore, M., Olivari, F., Peroni, D., Romagnoli, E., Ruggiero, C., Saviola, G., Sella, S., Sfrappini, M., Silveri, F., Vantaggiato, E., Venturin, A., and Zuccaro, C.
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Fractures ,Osteoporosis ,Supplementation ,Vitamin D
354. Ultrasonography vs. clinical examination in children with suspected arthritis. Does it make sense to use poliarticular ultrasonographic screening?
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Georgios Filippou, Cantarini, L., Bertoldi, I., Picerno, V., Frediani, B., and Galeazzi, M.
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Male ,Synovitis ,Child, Preschool ,Prevalence ,Humans ,Mass Screening ,Female ,Child ,Physical Examination ,Sensitivity and Specificity ,Arthritis, Juvenile ,Ultrasonography - Abstract
Juvenile idiopathic arthritis (JIA) is a term that encompasses all forms of arthritis that begin before the age of 16 years old, persist for more than 6 weeks and are of unknown cause. The ILAR criteria for JIA classification are based on the number of joints involved. The aim of our study was to compare clinical evaluation and ultrasonography (US) in the assessment of joint synovitis in children with suspected JIA.We enrolled in our study all children who presented at our outpatient clinic of Paediatric Rheumatology with suspected JIA. All the children underwent a clinical examination for joint swelling (40 joints), a tender joint count (42 joints) and US examination (42 joints) on the same day. They all returned to the clinic after approximately 2 weeks with the results of the tests prescribed at the first visit and a diagnosis was formulated.Thirty-one children were enrolled. More synovitis was identified by US than by than clinical examination (42 joints vs. 27). Clinical examination classified as swollen 13 joints that did not result affected at US. Of the 94 painful joints, 24 were affected by synovitis at US. The final diagnoses were: 9 children with JIA (any form), 9 were classified as healthy and 13 with other diseases. One child was reclassified and 2 were diagnosed with JIA thanks to US.US detected more synovitis than clinical examination in children with suspected JIA, therefore, US should be included in the screening procedure of children with suspected JIA.
355. Ultrasonographic study of Achilles tendon and plantar fascia in chondrocalcinosis
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Falsetti, P., Frediani, B., Acciai, C., Baldi, F., Georgios Filippou, Prada, E. P., Sabadini, L., and Marcolongo, R.
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Adult ,Aged, 80 and over ,Male ,Foot ,Reproducibility of Results ,Chondrocalcinosis ,Ultrasonography, Doppler ,Middle Aged ,Calcium Pyrophosphate ,Achilles Tendon ,Radiography ,Fasciitis, Plantar ,Osteoarthritis ,Synovial Fluid ,Humans ,Female ,Fascia ,Aged - Abstract
To investigate by high frequency grey-scale ultrasonography (US) and power Doppler sonography (PDS) the modality and frequency of involvement of the Achilles tendon and plantar fascia in chondrocalcinosis (CC), and to correlate these findings with clinical complaints and radiographic evidence.The heels of 57 consecutive patients with CC were evaluated by US, PDS, and radiography. One control group of 50 consecutive patients with osteoarthritis (OA) without signs of CC was studied in the same way. A second control group of 50 healthy subjects underwent only US/PDS examination. All subjects also underwent clinical assessment.US revealed Achilles tendon calcifications in 57.9% of those with CC, but none in the control groups. Plantar fascia calcifications were observed in 15.8% of CC and in 2% of OA cases, but not in healthy controls. US showed no significant difference in postero-inferior and inferior calcaneal enthesophytosis between subjects with CC (59.6% and 61.4%, respectively) and those with OA (46% and 44%, respectively). Such alterations were also present, in lower percentages, in the healthy controls. Posterior and inferior calcaneal erosions were absent in all groups. Achilles enthesopathy was found in 22.8% of patients with CC (14.9% of heels, with vascular signals in 11.4% of heels on PDS). Deep retrocalcaneal bursitis was found in 10.5% of patients with CC (7% of heels, with vascular signals in 5.2% of heels on PDS). Plantar fasciitis was found in 40.3% of patients with CC (36% of heels, with vascular signals in 2.6% of heels on PDS) and in 14% of OA patients, but not in healthy controls. No significant correlation was found between talalgia or sex of patients and presence of calcifications. A significant correlation was observed between talalgia and Achilles enthesopathy (r = 0.78, p0.0001), deep retrocalcaneal bursitis (r = 0.7, p0.0001), and plantar fasciitis (r = 0.31, p0.001). A significant correlation between talalgia and vascular signals on PDS was observed in Achilles enthesopathy (r = 0.91, p0.0001) and deep retrocalcaneal bursitis (r = 0.65, p0.0001). The presence of vascular signals on PDS was significantly associated with the presence of tendinous and bursal grey-scale US alterations. Achilles tendon calcifications were 39% sensitive, 100% specific, and 77% accurate for the presence of CC, whereas plantar fascia calcifications were 15% sensitive, 98% specific, and 54% accurate. Excellent agreement was found between US and radiography in detecting Achilles tendon calcifications (k = 0.86), plantar fascia calcifications (k = 0.77), postero-inferior enthesophytosis (k = 0.90), and inferior enthesophytosis (k = 0.83).Calcaneal tendon calcifications are frequent and asymptomatic findings in patients with CC, and they have a high specificity for this disease. US shows high agreement with radiography in depicting calcifications and enthesophytosis. Inflammatory changes of the calcaneal soft tissues are frequently observed by US and PDS in patients with chondrocalcinosis.
356. Efficacy of monoclonal anti-tumour necrosis factor-α antibodies in uveitic macular oedema
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Gm, Tosi, Vitale A, Rigante D, Sota J, Emmi G, Lopalco G, Guerriero S, Iannone F, Vannozzi L, Bitossi A, Frediani B, Cantarini L, and Claudia Fabiani
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Settore MED/16 - REUMATOLOGIA ,Tumor Necrosis Factor-alpha ,Visual Acuity ,Adalimumab ,Golimumab ,Macular Edema ,Adalimumab, Certolizumab, Golimumab, Infliximab, Uveitis ,Infliximab ,Uveitis ,Treatment Outcome ,Certolizumab ,Humans ,Tomography, Optical Coherence ,Follow-Up Studies ,Retrospective Studies - Abstract
To assess the efficacy of anti-tumour necrosis factor (TNF)-α agents in the treatment of refractory uveitic macular oedema (UME).Patients with refractory UME treated with TNF-α blockers were retrospectively enrolled. Central macular thickness (CMT) was assessed at optical coherence tomography (OCT) at the start of TNF-α inhibition, after 3 and 12 months, and at the last follow-up visit.Thirty-six patients (56 eyes with UME) were enrolled. The mean follow-up period was 29.9±40.8 (4-184) months. A statistically significant decrease was observed in the frequency of UME (p0.0001) and in the mean CMT values (p0.0001) during the study period. Best corrected visual acuity improved in 35 eyes (62.5%), remained stable in 12 eyes (21.4%), reduced in 9 eyes (16.1%). The mean corticosteroid dosage significantly decreased during the study period (p=0.016).TNF-α inhibitors represent a useful treatment in patients with severe or resistant UME.
357. The eye involvement in monogenic autoinflammatory diseases: literature review and update
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Sota, J., Vitale, A., Fabiani, C., Frediani, B., Donato Rigante, Tosi, G. M., Zannin, M. E., and Cantarini, L.
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Settore MED/16 - REUMATOLOGIA ,Eye Diseases ,Hereditary Autoinflammatory Diseases ,Autoinflammatory diseases ,Immunology ,Keratoconus ,Macular Edema ,Retinitis pigmentosa ,Uveitis ,Retinal vasculitis ,Scleritis ,Rheumatology ,Immunology and Allergy ,Autoinflammation ,Humans ,Papilledema - Abstract
Monogenic autoinflammatory diseases (AIDs) are rare entities characterised by improper activation of the innate immune system. This in turn determines recurrent episodes of systemic inflammation characterised by fever, which is variously combined with a wide range of inflammatory manifestations involving the skin, joints, serous membranes, gastrointestinal tract, and central nervous system. As shown by research efforts conducted during the last decade, the eye is not exempt from the systemic inflammatory process and may be involved in almost all of the most frequent AIDs, with several distinct peculiarities. Ocular affections may severely impact patients' quality of life due to orbital pain, impairment of visual acuity, and/ or long-term, sight-threatening complications. Consequently, in the context of a multidisciplinary team, ophthalmologists should be aware of ocular manifestations related to these disorders as they may have a dominant diagnostic weight in patients with a challenging presentation as well as a salient role in therapeutic choice in sight-threatening situations. This review describes a variety of aspects of ophthalmologic involvement in AIDs, looking at both well-recognised eye manifestations as well as rarely reported ocular presentations, with a particular focus on the recent literature.
358. Correlation of Serum Amyloid-A Levels, Clinical Manifestations, Treatment, and Disease Activity in Patients with Behçet's Disease
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Sota J, Vitale A, Rigante D, Orlando I, Om, Lucherini, Simpatico A, Lopalco G, Franceschini R, Galeazzi M, Frediani B, Fabiani C, Gm, Tosi, and Luca Cantarini
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Adult ,Male ,Behçet’s disease current activity form (BDCAF) ,Serum Amyloid A Protein ,Behcet Syndrome ,Serum amyloid-A (SAA) ,Middle Aged ,Severity of Illness Index ,Uveitis ,Behçet’s disease ,Biological Factors ,Antirheumatic Agents ,Behçet’s disease, Behçet’s disease current activity form (BDCAF), Biomarkers, Serum amyloid-A (SAA), Uveitis ,Humans ,Female ,Biomarkers ,Retrospective Studies - Abstract
Behçet's disease (BD) is an inflammatory disorder potentially leading to life- and sight-threatening complications. No laboratory marker correlating with disease activity or predicting the occurrence of disease manifestations is currently available.To determine an association between serum amyloid-A (SAA) levels and disease activity via the BD Current Activity Form (BDCAF), to evaluate disease activity in relation to different SAA thresholds, to examine the association between single organ involvement and the overall major organ involvement with different SAA thresholds, and to assess the influence of biologic therapy on SAA levels.We collected 95 serum samples from 64 BD patients. Related demographic, clinical, and therapeutic data were retrospectively gathered.No association was identified between SAA levels and BD disease activity (Spearman's rho = 0.085, P = 0.411). A significant difference was found in the mean BDCAF score between patients presenting with SAA levels200 mg/L and those with SAA levels200 mg/L (P = 0.027). SAA levels200 mg/L were associated with major organ involvement (P = 0.008). A significant association was found between SAA levels150 mg/dl and ocular (P = 0.008), skin (P = 0.002), and mucosal (P = 0.012) manifestations. Patients undergoing biologic therapies displayed more frequently SAA levels200 mg/L vs. patients who were not undergoing biologic therapies (P = 0.012).Although SAA level does not represent a biomarker for disease activity, it might be a predictor of major organ involvement and ocular disease relapse at certain thresholds in patients with BD.
359. Epidemiological profile of non-infectious uveitis from the rheumatologist's perspective: A survey from two tertiary referral centres in Italy
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Lopalco, G., Venerito, V., Sota, J., Donato Rigante, Guerriero, S., Orlando, I., Franceschini, R., Favale, R., Lapadula, G., Castelli, B., Frediani, B., Galeazzi, M., La Torre, F., Iannone, F., Tosi, G. M., Fabiani, C., and Cantarini, L.
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Adult ,Male ,Non-infectious uveitis ,Time Factors ,Settore MED/16 - REUMATOLOGIA ,Adolescent ,Idiopathic uveitis ,Tertiary Care Centers ,Young Adult ,Rheumatology ,Panuveitis ,Humans ,Retrospective Studies ,Behçet's disease ,Uveitis, Posterior ,Middle Aged ,Prognosis ,Health Surveys ,Uveitis, Anterior ,Ankylosing spondylitis, Behçet's disease, Intraocular inflammation, Non-infectious uveitis, Treatment ,Treatment ,Italy ,Intraocular inflammation ,Female ,Rheumatologists ,Ankylosing spondylitis - Abstract
To describe the epidemiology of non-infectious uveitis (NIU) in two tertiary referral rheumatology units in Central and Southern Italy.Two hundred and seventy-eight consecutive NIU patients (417 eyes) evaluated between January 2016 and January 2017 were enrolled. Collected data were analysed in accordance with the primary anatomic site of inflammation, clinical course, and laterality.The mean age at NIU onset was 36.92±18.30 years with a female-to-male ratio of 1.34:1. Anterior uveitis (AU) was identified in 151 (54.32%), posterior uveitis (PU) in 67 (24.10%), intermediate uveitis (IU) in 5.40% and panuveitis (PanU) in 16.19% patients. Bilateral involvement was identified in 50% of our cohort. Uveitis was acute in 33.81% of patients, while 24.46% and 41.73% had a chronic and recurrent course, respectively. Gender and laterality did not influence the anatomical pattern, while disease course was significantly more acute or chronic in AU (p0.05) and chronic in IU (p0.05). An associated systemic disease was identified in 116 patients (41.73%). Twenty-seven patients (9.7%) had a specific isolated eye disease, 135 patients (48.56%) had idiopathic NIU. Uveitis associated with a systemic disease was significantly bilateral (p=0.01) and acute or chronic (p0.0001), while the isolated form showed an association with chronic course (p0.0001) and unilaterality (p=0.01).The most common anatomic pattern of NIU has been AU, followed by PU, PanU and IU. A systemic disease (mainly Behçet's disease, ankylosing spondylitis and juvenile idiopathic arthritis) has been recognised in a fair proportion of the entire cohort. The rheumatologist should remain a central professional figure in the multidisciplinary team dealing with intraocular inflammation on a daily basis.
360. FIRST REPORT OF CIRCULATING MICRORNAS IN TUMOUR NECROSIS FACTOR RECEPTOR-ASSOCIATED PERIODIC SYNDROME (TRAPS)
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Galeazzi, M., Obici, L., Ferracin, M., valerio fulci, Mcdermott, M. F., Lucherini, O. M., Merlini, G., Dickie, L., Muscari, I., Frediani, B., Negrini, M., Cimaz, R., and Cantarini, L.
361. Epidemiological profile of non-infectious uveitis from the rheumatologist's perspective: a survey from two tertiary referral centres in Italy
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Lopalco G, Venerito V, Sota J, Rigante D, Guerriero S, Orlando I, Franceschini R, Favale R, Lapadula G, Castelli B, Frediani B, Galeazzi M, and Luca Cantarini
362. Clinical determinants of bone mass and bone ultrasonometry in patients with systemic sclerosis
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Frediani, B., Baldi, F., Falsetti, P., Acciai, C., Filippou, G., Adriano Spreafico, Siagri, C., Chellini, F., Capperucci, C., Filipponi, P., Galeazzi, M., and Marcolongo, R.
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Adult ,Scleroderma, Systemic ,Blood Sedimentation ,Middle Aged ,Bone and Bones ,Calcaneus ,Absorptiometry, Photon ,C-Reactive Protein ,Premenopause ,Bone Density ,Humans ,Osteoporosis ,Female ,Menopause ,Aged ,Autoantibodies ,Ultrasonography - Abstract
The aim of this study was to evaluate bone mass and bone ultrasonometry in patients affected with systemic sclerosis (SSc).Fifty-five patients (mean age 54.1 +/- 14.1 years; 25 premenopausal, and 30 postmenopausal women) affected with SSc (in a limited, intermediate or diffused form) and 60 age-matched healthy controls (30 premenopausal, and 30 postmenopausal women) were studied for Bone Mineral Density (BMD) measured by fan-beam x-ray densitometry, Stiffness Index (SI) measured by ultrasonometry of the heel, inflammation indices (erithrocyte sedimentation rate, C-reactive protein), and autoantibodies (ANA, ENA). Examinations were also carried out in order to determine any internal organ involvement. None of the patients had previously received steroid treatment.BMD was significantly lower in the SSc group than in the control group, whether it was expressed in g/cm2 (lumbar spine: 0.980 vs 1.241, p0.01; femoral neck: 0.832 vs 0.955, p0.05; total body 1.050 vs 1.168, p0.01) or by T- and Z-score (lumbar spine: T = -2.48; Z = -1.10; femoral neck: T = -1.69; Z = -0.55; total body: T = -1.11; Z = -0.48). SI was also altered (75.8 vs 96.2, p0.01; T = -2.10, Z = -1.12). BMD and SI were lower in women with the diffuse form of skin involvement. BMD and SI were lower in women in whom one or more internal organs were involved.SSc patients had reduced BMD and SI that was more marked in the diffuse form and in those with internal organ involvement and that became more marked with age and estrogen deficiency. This demineralisation was not related to the inflammation indices, disease duration, or to the immunological pattern.
363. Efficacy and safety of certolizumab pegol and golimumab in the treatment of non-infectious uveitis
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Tosi, G. M., Sota, J., Vitale, A., Rigante, D., Emmi, G., Lopalco, G., Silvana Guerriero, Orlando, I., Iannone, F., Frediani, B., Angotti, R., Messina, M., Galeazzi, M., Vannozzi, L., Cantarini, L., and Fabiani, C.
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Male ,Uveitis ,Settore MED/16 - REUMATOLOGIA ,Treatment Outcome ,Tumor Necrosis Factor-alpha ,Certolizumab Pegol ,Antibodies, Monoclonal ,Humans ,Female ,Retrospective Studies - Abstract
The aim of the study was to evaluate the efficacy of golimumab (GOL) and certolizumab pegol (CZP) as additional treatment options for the treatment of uveitis.Patients with longstanding uveitis receiving either GOL or CZP were retrospectively evaluated in terms of frequency of ocular flares, drug survival, changes in best corrected visual acuity (BCVA) and steroid-sparing effect.Twenty-one patients (30 eyes), 17 of whom being female, were enrolled in the study; 16 out of 21 patients had been previously treated with other tumour necrosis factor (TNF)-α blockers. A significant reduction in ocular flares (from 128.6 bouts for 100 patients-year to 42.9 events for 100 patients-year) was observed between the 12 months prior to the start of GOL or CZP and the 12 months thereafter (p=0.01). The 36-month drug survival was 54.5% for CZP and 50.0% for GOL with no statistically significant differences between the two biologic agents. No differences were detected concerning BCVA values and the mean corticosteroid intake between baseline and the last follow-up. The safety profile was excellent.GOL and CZP represent effective and safe treatment choices for patients with uveitis also when unsuccessfully treated with other anti-TNF-α drugs, permitting a significant reduction in the frequency of ocular flares and preserving visual function with a good long-term retention rate.
364. Extracorporeal shock wave therapy in the treatment of inferior calcaneal enthesophytosis: outcome by fan-beam dual x ray absorptiometry (DXA).
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Cosentino, R., Frediani, B., De. Stefano, R., Acciai, C., Manca, S., Selvi, E., Frati, E., and Marcolongo, R.
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- 2004
- Full Text
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365. Determinants of Bone Turnover Markers in Healthy Premenopausal Women.
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Adami, S., Bianchi, G., Brandi, M. L., Giannini, S., Ortolani, S., Dimunno, O., Frediani, B., and Rossini, M.
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PERIMENOPAUSE - Abstract
An abstract of the article "Determinants of Bone Turnover Markers in Healthy Premenopausal Women," by S. Adami, G. Bianchi, M.L. Brandi, S. Giannini, S. Ortolani, O. Dimunno, B. Frediani and M. Rossini is presented.
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- 2008
366. Impact of smoking habit on adult-onset Still’s disease prognosis, findings from a multicentre observational study
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Giuliana Guggino, Luisa Costa, Carlomaurizio Montecucco, Daniela Iacono, Luca Cantarini, Ilenia Di Cola, Federico Perosa, Silvia Balduzzi, Fabiola Atzeni, Gelsomina Rozza, Ilenia Pantano, Stefano De Ludovico, Roberto Giacomelli, Piero Ruscitti, Paola Cipriani, Antonio Vitale, Marcella Prete, Silvia Rossi, Onorina Berardicurti, Luca Navarini, Alessandro Conforti, Francesco Caso, Francesco Ciccia, Bruno Frediani, Ruscitti P., Di Cola I., Berardicurti O., Conforti A., Iacono D., Pantano I., Rozza G., Rossi S., De Ludovico S., Balduzzi S., Vitale A., Caso F., Costa L., Prete M., Navarini L., Atzeni F., Guggino G., Perosa F., Cantarini L., Frediani B., Montecucco C., Ciccia F., Giacomelli R., Cipriani P., Ruscitti, P., Di Cola, I., Berardicurti, O., Conforti, A., Iacono, D., Pantano, I., Rozza, G., Rossi, S., De Ludovico, S., Balduzzi, S., Vitale, A., Caso, F., Costa, L., Prete, M., Navarini, L., Atzeni, F., Guggino, G., Perosa, F., Cantarini, L., Frediani, B., Montecucco, C., Ciccia, F., Giacomelli, R., and Cipriani, P.
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Adult ,medicine.medical_specialty ,Abdominal pain ,Adult-onset ,Macrophage activation syndrome ,Mortality ,Smoking ,Still’s disease ,Pericarditis ,Rheumatology ,Internal medicine ,Risk of mortality ,Humans ,Medicine ,Retrospective Studies ,business.industry ,Retrospective cohort study ,General Medicine ,Prognosis ,medicine.disease ,Cohort ,medicine.symptom ,business ,Still's Disease, Adult-Onset ,Serositis - Abstract
The objective of this study is to describe the possible prognostic impact of smoking habit on adult-onset Still’s disease (AOSD) patients, by the assessment of clinical characteristics, life-threatening complications occurrence, and mortality in smokers than non-smokers. A multicentre retrospective study of prospectively followed-up AOSD patients included in Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale (GIRRCS) cohort was conducted. Out of 185 AOSD assessed patients, 45 smokers were identified. These showed a higher frequency of pericarditis (35.5% vs 16.4%, p = 0.011), pleuritis (33.3% vs 14.3%, p = 0.008), and abdominal pain (17.7% vs 6.4%, p = 0.035). Furthermore, smokers showed higher values of systemic score (6.4 ± 2.2 vs 5.4 ± 1.8, p = 0.004), an increased rate of macrophage activation syndrome (MAS) (28.9% vs 6.4%, p < 0.0001) and of parenchymal lung disease (17.7% vs 12.6%, p = 0.035). Although not significant, these patients more frequently experienced a poor prognosis (13.3% vs 4.3%, p = 0.074). Smoking habit predicted MAS occurrence in both univariate (HR: 5.98, 95% CI: 2.45–14.57, p < 0.0001) and multivariate regression models (HR: 6.21, 95% CI: 2.46–15.70, p < 0.0001). Smokers had a significant higher risk of parenchymal lung disease in both univariate (HR: 3.97, 95% CI: 1.43–11.02, p = 0.008) and multivariate regression models (HR: 3.90, 95% CI: 1.36–11.23, p = 0.012). Smoking habit also increased the risk of mortality in univariate regression model (HR: 4.25, 95% CI: 1.33–13.55, p = 0.015). Smoking habit resulted to be a negative prognostic factor on AOSD patients. Smokers were characterised by a higher frequency of serositis and higher values of systemic score. Additionally, these patients were more frequently burdened by MAS and parenchymal lung disease associated with a poor prognosis.Key points•Smoking habit resulted to be a negative prognostic factor on AOSD.•Smokers were characterised by an increased frequency of serositis and higher values of systemic score.•Cigarette exposure was associated with MAS and parenchymal lung disease in AOSD.
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- 2021
367. Neridronate for transient osteoporosis of the hip in a child.
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Gaggiano, C., Bardelli, M., Tarsia, M., Gentileschi, S., Maselli, A., Grosso, S., Cantarini, L., and Frediani, B.
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DIPHOSPHONATES , *HIP joint , *CONVALESCENCE , *MAGNETIC resonance imaging , *OSTEOPOROSIS , *VITAMIN D , *FEMORAL fractures , *CHILDREN - Abstract
Transient osteoporosis of the hip (TOH) is usually reported in middle-aged men or during pregnancy as a benign self-limiting condition. Nevertheless, its impact on quality of life in terms of pain and disability is considerable. Also, it can lead to insufficiency fractures or, more rarely, evolve into osteonecrosis. This condition is anecdotally described in the pediatric age and very little is known about how it may affect the growing bone. We herein describe a case of TOH in a 10-year-old child treated at our pediatric rheumatology service and summarize the pediatric cases of TOH previously reported in literature. There are two points of interest in our case report, the first one being the unusual complication of TOH with a femoral physis fracture and the second the complete recovery after the off-label therapy with bisphosphonates. We suggest that interventional medical treatment could be considered in selected cases of juvenile TOH, to prevent any possible irreversible damage on the femoral physis. As far as we know, this is the first report of neridronate employment in children affected by TOH. [ABSTRACT FROM AUTHOR]
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- 2022
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368. Genetic mechanisms of critical illness in COVID-19
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Pairo-Castineira, Erola, Clohisey, Sara, Klaric, Lucija, Bretherick, Andrew D, Rawlik, Konrad, Pasko, Dorota, Walker, Susan, Parkinson, Nick, Fourman, Max Head, Russell, Clark D, Furniss, James, Richmond, Anne, Gountouna, Elvina, Wrobel, Nicola, Harrison, David, Wang, Bo, Yang, Wu, Meynert, Alison, Griffiths, Fiona, Oosthuyzen, Wilna, Kousathanas, Athanasios, Moutsianas, Loukas, Yang, Zhijian, Zhai, Ranran, Zheng, Chenqing, Grimes, Graeme, Beale, Rupert, Millar, Jonathan, Shih, Barbara, Keating, Sean, Zechner, Marie, Haley, Chris, Porteous, David J, Hayward, Caroline, Yang, Jian, Knight, Julian, Summers, Charlotte, Shankar-Hari, Manu, Klenerman, Paul, Turtle, Lance, Antonia, Ho, Moore, Shona C, Hinds, Charles, Horby, Peter, Nichol, Alistair, Maslove, David, Ling, Lowell, Mcauley, Danny, Montgomery, Hugh, Walsh, Timothy, Pereira, Alexandre C, Renieri, Johnny, Millar, Alistair, Nichol, Tim, Walsh, Manu, Shankar-Hari, Chris, Ponting, Jen, Meikle, Paul, Finernan, Ellie, Mcmaster, Andy, Law, J Kenneth Baillie, Trevor, Paterson, Tony, Wackett, Ruth, Armstrong, Richard, Clark, Audrey, Coutts, Lorna, Donnelly, Tammy, Gilchrist, Katarzyna, Hafezi, Louise, Macgillivray, Alan, Maclean, Sarah, Mccafferty, Kirstie, Morrice, Jane, Weaver, Ceilia, Boz, Ailsa, Golightly, Mari, Ward, Hanning, Mal, Helen, Szoor-McElhinney, Adam, Brown, Ross, Hendry, Andrew, Stenhouse, Louise, Cullum, Dawn, Law, Sarah, Law, Rachel, Law, Maaike, Swets, Nicky, Day, Filip, Taneski, Esther, Duncan, Nicholas, Parkinson, Collier, D, Wood, S, Zak, A, Borra, C, Matharu, M, May, P, Alldis, Z, Mitchelmore, O, Bowles, R, Easthope, A, Bibi, F, Lancoma-Malcolm, I, Gurasashvili, J, Pheby, J, Shiel, J, Bolton, M, Patel, M, Taylor, M, Zongo, O, Ebano, P, Harding, P, Astin-Chamberlain, R, Choudhury, Y, Cox, A, Kallon, D, Burton, M, Hall, R, Blowes, S, Prime, Z, Biddle, J, Prysyazhna, O, Newman, T, Tierney, C, Kassam, J, Shankar-Hari, M, Ostermann, M, Campos, S, Bociek, A, Lim, R, Grau, N, O Jones, T, Whitton, C, 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Konrad [0000-0002-0010-370X], Walker, Susan [0000-0002-5016-6426], Fourman, Max Head [0000-0001-7381-2278], Russell, Clark D [0000-0002-9873-8243], Gountouna, Elvina [0000-0001-7870-2780], Wang, Bo [0000-0002-1580-797X], Wu, Yang [0000-0002-0128-7280], Kousathanas, Athanasios [0000-0001-6265-6521], Moutsianas, Loukas [0000-0001-5453-345X], Zhai, Ranran [0000-0002-5834-9120], Beale, Rupert [0000-0002-6705-8560], Keating, Sean [0000-0001-8552-5604], Haley, Chris [0000-0002-9811-0210], Porteous, David J [0000-0003-1249-6106], Hayward, Caroline [0000-0002-9405-9550], Yang, Jian [0000-0003-2001-2474], Knight, Julian [0000-0002-0377-5536], Summers, Charlotte [0000-0002-7269-2873], Shankar-Hari, Manu [0000-0002-5338-2538], Turtle, Lance [0000-0002-0778-1693], Moore, Shona C [0000-0001-8610-2806], Hinds, Charles [0000-0001-5094-8324], McAuley, Danny [0000-0002-3283-1947], Montgomery, Hugh [0000-0001-8797-5019], Renieri, Alessandra [0000-0002-0846-9220], Shen, Xia [0000-0003-4390-1979], 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T., Massey, E., Croston, G., Reschreiter, H., Camsooksai, J., Patch, S., Jenkins, S., Humphrey, C., Wadams, B., Msiska, M., Adanini, O., Attwood, B., Parsons, P., Tatham, K., Jhanji, S., Black, E., Dela Rosa, A., Howle, R., Thomas, B., Bemand, T., Raobaikady, R., Saha, R., Staines, N., Daniel, A., Finn, J., Hutter, J., Doble, P., Shovelton, C., Pawley, C., Kannan, T., Hill, M., Combes, E., Monnery, S., Joefield, T., Popescu, M., Thankachen, M., Oblak, M., Little, J., Mcivor, S., Brady, A., Whittle, H., Prady, H., Chan, R., Ahmed, A., Morris, A., Gibson, C., Gordon, E., Keenan, S., Quinn, H., Benyon, S., Marriott, S., Zitter, L., Park, L., Baines, K., Lyons, M., Holland, M., Keenan, N., Young, M., Garrioch, S., Dawson, J., Tolson, M., Scholefield, B., Bi, R., Richardson, N., Schumacher, N., Cosier, T., Millen, G., Higham, A., Turki, S., Allen, L., Crisp, N., Hazleton, T., Knight, A., Deery, J., Price, C., Turney, S., Tilbey, S., Beranova, E., Wright, D., George, L., Twiss, S., Wadd, S., Postlethwaite, K., Gondo, P., Masunda, B., Kayani, A., Hadebe, B., Whiteside, J., Clarke, N., Donnison, P., Trim, F., Leadbitter, I., Butcher, D., O'Sullivan, S., Purewal, B., Bell, S., Rivers, V., O'Leary, R., Birch, J., Collins, E., Anderson, S., Hammerton, K., Andrews, E., Burns, K., Edmond, I., Todd, A., Donnachie, J., Turner, P., Prentice, L., Symon, L., Runciman, N., Auld, F., Halkes, M., Mercer, P., Thornton, L., Debreceni, G., Wilkins, J., Crickmore, V., Subramanian, G., Marshall, R., Jennings, C., Latif, M., Bunni, L., Spivey, M., Bean, S., Burt, K., Linnett, V., Ritzema, J., Sanderson, A., Mccormick, W., Bokhari, M., Kapoor, R., Loader, D., Ayers, A., Harrison, W., North, J., Belagodu, Z., Paramsothy, R., Olufuwa, O., Gherman, A., Fuller, B., Stuart, C., Kelsall, O., Davis, C., Wild, L., Wood, H., Thrush, J., Durie, A., Austin, K., Archer, K., Anderson, P., Vigurs, C., Thorpe, C., Knights, E., Boyle, N., Price, A., Kubisz-Pudelko, A., Wood, D., Lewis, A., Board, S., Pippard, L., Perry, J., Beesley, K., Rattray, A., Lee, E., Lennon, L., Douglas, K., Bell, D., Boyle, R., Glass, L., Nauman Akhtar, M., Dent, K., Potoczna, D., Pearson, S., Horsley, E., Spencer, S., Mullan, D., Skinner, D., Gaylard, J., Barber, R., Hewitt, C., Hilldrith, A., Shepardson, S., Wills, M., Jackson-Lawrence, K., Gupta, A., Timlick, E., Gorman, C., Otahal, I., Gales, A., Coetzee, S., Sell, C., Raj, M., Peiu, M., Quaid, S., Watson, E., Elliott, K., Mallinson, J., Chandler, B., Turnbull, A., Finch, C., Holl, C., Cooper, J., Evans, A., Khaliq, W., Collins, A., Gude, E. T., Love, N., van Koutrik, L., Hunt, J., Kaye, D., Fisher, E., Brayne, A., Tuckey, V., Jackson, P., Parkin, J., Tariq, A., Houlden, H., Tucci, A., Hardy, J., Moncur, E., Highgate, J., Cowley, A., Mitra, A., Stead, R., Behan, T., Burnett, C., Newton, M., Heeney, E., Pollard, R., Hatton, J., Patel, A., Kasipandian, V., Allibone, S., Genetu, R. M., O'Brien, L., Omar, Z., Perkins, E., Davies, K., Tetla, D., Shelley, B., Irvine, V., Williams, S., Williams, P., Goodsell, J., Tutton, R., Bough, L., Winter-Goodwin, B., Kitson, R., Pinnell, J., Wilson, A., Nortcliffe, T., Wood, T., Home, M., Holdroyd, K., Robinson, M., Shaw, R., Greig, J., Brady, M., Haigh, A., Matupe, L., Usher, M., Mellor, S., Dale, S., Gledhill, L., Shaw, L., Turner, G., Kelly, D., Anwar, B., Riley, H., Sturgeon, H., Ali, A., Thomis, L., Melia, D., Dance, A., Humphreys, S., Frost, I., Gopal, V., Godden, J., Holden, A., Swann, S., Smith, T., Clapham, M., Poultney, U., Harper, R., Rice, P., Reece-Anthony, R., Gurung, B., Moultrie, S., Odam, M., Mayer, A., Bellini, A., Pickard, A., Bryant, J., Roe, N., Sowter, J., Lang, K., Taylor, J., Barry, P., Hobrok, M., Tench, H., Wolf-Roberts, R., Mcguinness, H., Loosley, R., Hawcutt, D., Rad, L., O'Malley, L., Saunderson, P., Seddon, G., Anderson, T., Rogers, N., Ruddy, J., Harkins, M., Beith, C., Mcalpine, A., Ferguson, L., Grant, P., Macfadyen, S., Mclaughlin, M., Baird, T., Rundell, S., Welsh, B., Hamill, R., Fisher, F., Gregory, J., Campbell, A., Smuts, S., Kenneth Baillie, J., Carson, G., Alex, B., Bach, B., Barclay, W. S., Bogaert, D., Chand, M., Cooke, G. S., Docherty, A. B., Dunning, J., da Silva Filipe, A., Fletcher, T., Green, C. A., Harrison, E. M., Hiscox, J. A., Ho, A. Y. W., Horby, P. W., Ijaz, S., Khoo, S., Lim, W. S., Mentzer, A. J., Merson, L., Meynert, A. M., Noursadeghi, M., Palmarini, M., Paxton, W. A., Pollakis, G., Price, N., Rambaut, A., Robertson, D. L., Sancho-Shimizu, V., Scott, J. T., de Silva, T., Sigfrid, L., Solomon, T., Sriskandan, S., Stuart, D., Tedder, R. S., Thomson, E. C., Thompson, A. A. R., Thwaites, R. S., Turtle, L. C. W., Zambon, M., Hardwick, H., Donohue, C., Lyons, R., Norman, L., Pius, R., Drake, T. M., Fairfield, C. J., Knight, S. R., Mclean, K. A., Murphy, D., Shaw, C. A., Dalton, J., Girvan, M., Saviciute, E., Roberts, S., Harrison, J., Marsh, L., Connor, M., Halpin, S., Gamble, C., Leeming, G., Wham, M., Greenhalf, W., Shaw, V., Mcdonald, S., Ganna, A., Sulem, P., van Heel, D. A., Cordioli, M., Sveinbjornsson, G., Niemi, M. E. K., Shelton, J. F., Shastri, A. J., Ye, C., Weldon, C. H., Filshtein-Sonmez, T., Coker, D., Symons, A., Esparza-Gordillo, J., Aslibekyan, S., Auton, A., Krieger, J. E., Marques, E., Jannes, C. E., Mari, F., Daga, S., Baldassarri, M., Benetti, E., Furini, S., Fallerini, C., Fava, F., Valentino, F., Doddato, G., Giliberti, A., Tita, R., Amitrano, S., Bruttini, M., Croci, S., Meloni, I., Pinto, A. M., Frullanti, E., Mencarelli, M. A., Rizzo, C. L., Montagnani, F., Di Sarno, L., Tommasi, A., Palmieri, M., Emiliozzi, A., Fabbiani, M., Rossetti, B., Zanelli, G., Bargagli, E., Bergantini, L., D'Alessandro, M., Cameli, P., Bennet, D., Anedda, F., Marcantonio, S., Scolletta, S., Franchi, F., Mazzei, M. A., Guerrini, S., Conticini, E., Cantarini, L., Frediani, B., Tacconi, D., Spertilli, C., Feri, M., Donati, A., Scala, R., Guidelli, L., Spargi, G., Corridi, M., Nencioni, C., Croci, L., Caldarelli, G. P., Spagnesi, M., Piacentini, P., Bandini, M., Desanctis, E., Cappelli, S., Canaccini, A., Verzuri, A., Anemoli, V., Ognibene, A., Vaghi, M., D'Arminio Monforte, A., Merlini, E., Mondelli, M. U., Mantovani, S., Ludovisi, S., Girardis, M., Venturelli, S., Sita, M., Cossarizza, A., Antinori, A., Vergori, A., Rusconi, S., Siano, M., Gabrieli, A., Riva, A., Francisci, D., Schiaroli, E., Scotton, P. G., Andretta, F., Panese, S., Scaggiante, R., Gatti, F., Parisi, S. G., Castelli, F., Quiros-Roldan, M. E., Magro, P., Zanella, I., Della Monica, M., Piscopo, C., Capasso, M., Russo, R., Andolfo, I., Iolascon, A., Fiorentino, G., Carella, M., Castori, M., Merla, G., Aucella, F., Raggi, P., Marciano, C., Perna, R., Bassetti, M., Di Biagio, A., Sanguinetti, M., Masucci, L., Valente, S., Mandala, M., Giorli, A., Salerni, L., Zucchi, P., Parravicini, P., Menatti, E., Baratti, S., Trotta, T., Giannattasio, F., Coiro, G., Lena, F., Coviello, D. A., Mussini, C., Bosio, G., Martinelli, E., Mancarella, S., Tavecchia, L., Crotti, L., Picchiotti, N., Gori, M., Gabbi, C., Sanarico, M., Ceri, S., Pinoli, P., Raimondi, F., Biscarini, F., Stella, A., Shen, X., Ponting, C. P., Fawkes, A., Tenesa, A., Caulfield, M., Scott, R., Rowan, K., Murphy, L., Openshaw, P. J. M., Semple, M. G., Vitart, V., and Wilson, J. F.
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0301 basic medicine ,Male ,CCR2 ,Chromosomes, Human, Pair 21 ,Genome-wide association study ,Receptor, Interferon alpha-beta ,Disease ,Bioinformatics ,Genome-wide association studies ,23andMe Investigators ,Interferon alpha-beta ,0302 clinical medicine ,Receptors ,2',5'-Oligoadenylate Synthetase ,Pair 12 ,genetics ,Lung ,BRACOVID Investigators ,Multidisciplinary ,GenOMICC Investigators ,Tyrosine kinase 2 ,030220 oncology & carcinogenesis ,Multigene Family ,Medical genetics ,Female ,Dipeptidyl-Peptidases and Tripeptidyl-Peptidase ,5'-Oligoadenylate Synthetase ,Human ,Receptor ,medicine.medical_specialty ,Critical Care ,Receptors, CCR2 ,General Science & Technology ,Critical Illness ,Chromosomes ,03 medical and health sciences ,Intensive care ,Mendelian randomization ,Immunogenetics ,medicine ,Humans ,Dipeptidyl-Peptidases and Tripeptidyl-Peptidases ,Gen-COVID Investigators ,Inflammation ,TYK2 Kinase ,Chromosomes, Human, Pair 12 ,Pair 19 ,SARS-CoV-2 ,business.industry ,Drug Repositioning ,COVID-19 ,United Kingdom ,COVID-19 Human Genetics Initiative ,030104 developmental biology ,Viral infection ,Chromosomes, Human, Pair 19 ,Genome-Wide Association Study ,Pharmacogenomics ,ISARICC Investigators ,Pair 21 ,2' ,business - Abstract
Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079,P=1.65×10−8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1,OAS2andOAS3); on chromosome 19p13.2 (rs74956615,P=2.3×10−8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069,P=3.98× 10−12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757,P=4.99×10−8) in the interferon receptor geneIFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression ofIFNAR2, or high expression ofTYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte–macrophage chemotactic receptorCCR2is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice.
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- 2020
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369. Effects of rituximab therapy on B cell differentiation and depletion.
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Bergantini, L., d'Alessandro, M., Cameli, P., Vietri, L., Vagaggini, C., Perrone, A., Sestini, P., Frediani, B., and Bargagli, E.
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B cell differentiation , *B cells , *CELLULAR therapy , *MONOCLONAL antibodies , *RITUXIMAB , *RHEUMATOID arthritis - Abstract
Rituximab is a human/murine chimeric anti-CD20 monoclonal antibody. It is largely used to treat B cell malignancies and has become standard in the management of B cell‑mediated diseases such as rheumatoid arthritis and granulomatosis with polyangitis. The effects of rituximab need to be monitored by B cell phenotyping. Evaluate possible surface markers for monitoring B cell development in response to rituximab treatment. This review discusses the literature on the B cell surface markers analysed by flow cytometry in patients treated with rituximab. A panel of biomarkers of response to treatment to monitor by flow cytometry is also suggested. B cell phenotyping is useful to predict clinical relapses after rituximab treatment. The proposed panel of biomarkers includes CD38++CD24++IgD+/− immature B cells and IgD−CD38+/− memory B cells. In responders, Th1/Th2 balance and tolerance cells (CD4+CD25+CD127−/low Treg cells and CD19+CD24hiCD38hi Breg cells) tend to be restored after rituximab therapy. Furthermore, in responder patients, indirect depletion of CD19+/-CD27++CD38++ preplasma cells can be proposed as a predictor of response. Flow cytometric analysis of samples from patients treated with rituximab is a useful strategy to stratify patients according to response to treatment. Identification of B cell differentiation stages by means of a specific flow cytometry panel could improve monitoring of rituximab effects and enable non-responders to be distinguished from good responders. [ABSTRACT FROM AUTHOR]
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- 2020
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370. A systematic review on the performance of fracture risk assessment tools: FRAX, DeFRA, FRA-HS
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G. Adami, A. Biffi, G. Porcu, R. Ronco, R. Alvaro, R. Bogini, A. P. Caputi, L. Cianferotti, B. Frediani, D. Gatti, S. Gonnelli, G. Iolascon, A. Lenzi, S. Leone, S. Migliaccio, T. Nicoletti, M. Paoletta, A. Pennini, E. Piccirilli, U. Tarantino, M. L. Brandi, G. Corrao, M. Rossini, R. Michieli, Adami, G, Biffi, A, Porcu, G, Ronco, R, Alvaro, R, Bogini, R, Caputi, A, Cianferotti, L, Frediani, B, Gatti, D, Gonnelli, S, Iolascon, G, Lenzi, A, Leone, S, Migliaccio, S, Nicoletti, T, Paoletta, M, Pennini, A, Piccirilli, E, Tarantino, U, Brandi, M, Corrao, G, Rossini, M, and Michieli, R
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Endocrinology ,Secondary prevention ,Endocrinology, Diabetes and Metabolism ,Systematic review ,Fracture risk assessment ,Fragility fracture - Abstract
Purpose Preventing fragility fractures by treating osteoporosis may reduce disability and mortality worldwide. Algorithms combining clinical risk factors with bone mineral density have been developed to better estimate fracture risk and possible treatment thresholds. This systematic review supported panel members of the Italian Fragility Fracture Guidelines in recommending the use of best-performant tool. The clinical performance of the three most used fracture risk assessment tools (DeFRA, FRAX, and FRA-HS) was assessed in at-risk patients. Methods PubMed, Embase, and Cochrane Library were searched till December 2020 for studies investigating risk assessment tools for predicting major osteoporotic or hip fractures in patients with osteoporosis or fragility fractures. Sensitivity (Sn), specificity (Sp), and areas under the curve (AUCs) were evaluated for all tools at different thresholds. Quality assessment was performed using the Quality Assessment of Diagnostic Accuracy Studies-2; certainty of evidence (CoE) was evaluated using the Grading of Recommendations Assessment, Development and Evaluation approach. Results Forty-three articles were considered (40, 1, and 2 for FRAX, FRA-HS, and DeFRA, respectively), with the CoE ranging from very low to high quality. A reduction of Sn and increase of Sp for major osteoporotic fractures were observed among women and the entire population with cut-off augmentation. No significant differences were found on comparing FRAX to DeFRA in women (AUC 59–88% vs. 74%) and diabetics (AUC 73% vs. 89%). FRAX demonstrated non-significantly better discriminatory power than FRA-HS among men. Conclusion The task force formulated appropriate recommendations on the use of any fracture risk assessment tools in patients with or at risk of fragility fractures, since no statistically significant differences emerged across different prediction tools.
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- 2023
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371. Executive summary: Italian guidelines for diagnosis, risk stratification, and care continuity of fragility fractures 2021
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Corrao, Giovanni, Biffi, Annalisa, Porcu, Gloria, Ronco, Raffaella, Adami, Giovanni, Alvaro, Rosaria, Bogini, Riccardo, Caputi, Achille Patrizio, Cianferotti, Luisella, Frediani, Bruno, Gatti, Davide, Gonnelli, Stefano, Iolascon, Giovanni, Lenzi, Andrea, Leone, Salvatore, Michieli, Raffaella, Migliaccio, Silvia, Nicoletti, Tiziana, Paoletta, Marco, Pennini, Annalisa, Piccirilli, Eleonora, Rossini, Maurizio, Tarantino, Umberto, Brandi, Maria Luisa, Corrao, G, Biffi, A, Porcu, G, Ronco, R, Adami, G, Alvaro, R, Bogini, R, Caputi, A, Cianferotti, L, Frediani, B, Gatti, D, Gonnelli, S, Iolascon, G, Lenzi, A, Leone, S, Michieli, R, Migliaccio, S, Nicoletti, T, Paoletta, M, Pennini, A, Piccirilli, E, Rossini, M, Tarantino, U, and Brandi, M
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grade ,systematic review ,Endocrinology, Diabetes and Metabolism ,evidence-based guideline ,fragility fracture ,secondary prevention - Abstract
BackgroundFragility fractures are a major public health concern owing to their worrying and growing burden and their onerous burden upon health systems. There is now a substantial body of evidence that individuals who have already suffered a fragility fracture are at a greater risk for further fractures, thus suggesting the potential for secondary prevention in this field.PurposeThis guideline aims to provide evidence-based recommendations for recognizing, stratifying the risk, treating, and managing patients with fragility fracture. This is a summary version of the full Italian guideline.MethodsThe Italian Fragility Fracture Team appointed by the Italian National Health Institute was employed from January 2020 to February 2021 to (i) identify previously published systematic reviews and guidelines on the field, (ii) formulate relevant clinical questions, (iii) systematically review literature and summarize evidence, (iv) draft the Evidence to Decision Framework, and (v) formulate recommendations.ResultsOverall, 351 original papers were included in our systematic review to answer six clinical questions. Recommendations were categorized into issues concerning (i) frailty recognition as the cause of bone fracture, (ii) (re)fracture risk assessment, for prioritizing interventions, and (iii) treatment and management of patients experiencing fragility fractures. Six recommendations were overall developed, of which one, four, and one were of high, moderate, and low quality, respectively.ConclusionsThe current guidelines provide guidance to support individualized management of patients experiencing non-traumatic bone fracture to benefit from secondary prevention of (re)fracture. Although our recommendations are based on the best available evidence, questionable quality evidence is still available for some relevant clinical questions, so future research has the potential to reduce uncertainty about the effects of intervention and the reasons for doing so at a reasonable cost.
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- 2023
372. Similarities and differences between younger and older disease onset patients with newly diagnosed systemic lupus erythematosus
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Immacolata, Prevete, Annamaria, Iuliano, Alberto, Cauli, Matteo, Piga, Florenzo, Iannone, Laura, Coladonato, Alessandra, Bortoluzzi, Ettore, Silvagni, Chiara, Tani, Elena, Elefante, Andrea, Doria, Luca, Iaccarino, Franco, Franceschini, Micaela, Fredi, Fabrizio, Conti, Francesca Romana, Spinelli, Bruno, Frediani, Estrela, Gonzales Garcìa, Carlo A, Scirè, Anna, Zanetti, Davide, Rozza, Greta, Carrara, Gian Domenico, Sebastiani, Francesca, Bellisai, Prevete, I, Iuliano, A, Cauli, A, Piga, M, Iannone, F, Coladonato, L, Bortoluzzi, A, Silvagni, E, Tani, C, Elefante, E, Doria, A, Iaccarino, L, Franceschini, F, Fredi, M, Conti, F, Spinelli, F, Frediani, B, Garcia, E, Scire, C, Zanetti, A, Rozza, D, Carrara, G, and Sebastiani, G
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comorbiditie ,clinical features ,Rheumatology ,age onset ,systemic lupus erythematosus ,comorbidities ,Immunology ,Immunology and Allergy ,systemic lupus erythematosu ,clinical feature - Abstract
Objective Several studies show that age at onset has an impact on the clinical-serological presentation, comorbidities and disease course of patients with systemic lupus erythematosus (SLE). We evaluated whether, in patients with recent onset SLE, the age at onset correlates with clinical-serological manifestations and with comorbidities. Methods We analysed 171 patients with a SLE diagnosis obtained within 12 months of diagnosis enrolled in the Early Lupus project. Based on the age of onset of the first disease symptom, they were stratified into 2 groups: early onset (18–45 years) and late onset (>45 years). The analysis was replicated by stratifying patients based on age at diagnosis (fulfillment of ACR classification criteria). Each comparison was made at baseline and at 36 months of follow-up. Results Baseline: patients with late onset displayed comorbidities (hypertension, dyslipidaemia and osteoporosis) more frequently than early onset group. 11.4% of late onset patients had a malignancy in medical history, not recorded in the early onset cohort. The two groups differed neither in organ involvement (domain BILAG) nor in disease activity (ECLAM). Patients with early onset showed a disease with signs of higher serologic activity (higher frequency of anti-dsDNA positivity and lower mean C3 and C4 levels) and had malar rash more frequently than the late onset group (36.2% vs. 18.2%, p=0.042). Similar results were obtained by stratifying patients by age of diagnosis (18-45 years and >45 years), except for the higher frequency of discoid rash in the group with age at diagnosis >45 years (18% vs. 6.6%, p=0.045). 36 months: the 2 groups of patients independently of the stratification applied did not differ in the accumulation of damage, but showed a different pattern of 8 organ involvement. Musculoskeletal involvement was more frequent both in the late onset group (18.6% vs. 7.3%, p=0.043) and in the group with age at diagnosis >45 years (20.4% vs. 5.9%, p=0.009) compared to their counterparts, while renal involvement was more frequent in the group with age at diagnosis 18–45 years (21.4% vs. 6.1%, p=0.03).A sub analysis at 36 months on patients without hypertension and osteoporosis at enrollment showed that patients with older age at onset had a higher frequency of these comorbidities, compared to their counterparts. Conclusion In our cohort, younger disease SLE onset seems to correlate with a more active immunological profile, while late onset with a higher incidence of comorbidities.
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- 2023
373. Efficacy and safety of tocilizumab in adult-onset Still's disease: Real-life experience from the international AIDA registry
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Jurgen Sota, Antonio Vitale, Giuseppe Lopalco, Rosa Maria R. Pereira, Heitor F. Giordano, Isabele P.B. Antonelli, Joanna Makowska, Olga Brzezińska, Anna Lewandowska-Polak, Piero Ruscitti, Paola Cipriani, Ilenia Di Cola, Marcello Govoni, Francesca Ruffili, Petros P. Sfikakis, Katerina Laskari, Gaafar Ragab, Mohamed A. Hussein, Stefano Gentileschi, Carla Gaggiano, Francesco La Torre, Armin Maier, Giacomo Emmi, Achille Marino, Francesco Ciccia, Paolo Sfriso, Maria Cristina Maggio, Elena Bartoloni, Claudia Lomater, Mohamed Tharwat Hegazy, Maria Tektonidou, Marília A. Dagostin, Aleksandra Opinc, Gian Domenico Sebastiani, Roberto Giacomelli, Emanuela Del Giudice, Alma Nunzia Olivieri, Abdurrahman Tufan, Riza Kan Kardas, Rossana Nuzzolese, Fabio Cardinale, Ewa Więsik-Szewczyk, Parretti Veronica, Maria Tarsia, Florenzo Iannone, Francesca Della Casa, Claudia Fabiani, Bruno Frediani, Alberto Balistreri, Donato Rigante, Luca Cantarini, Sota, Jurgen, Vitale, Antonio, Lopalco, Giuseppe, Pereira, Rosa Maria R, Giordano, Heitor F, Antonelli, Isabele P B, Makowska, Joanna, Brzezińska, Olga, Lewandowska-Polak, Anna, Ruscitti, Piero, Cipriani, Paola, Cola, Ilenia Di, Govoni, Marcello, Ruffili, Francesca, Sfikakis, Petros P, Laskari, Katerina, Ragab, Gaafar, Hussein, Mohamed A, Gentileschi, Stefano, Gaggiano, Carla, La Torre, Francesco, Maier, Armin, Emmi, Giacomo, Marino, Achille, Ciccia, Francesco, Sfriso, Paolo, Maggio, Maria Cristina, Bartoloni, Elena, Lomater, Claudia, Hegazy, Mohamed Tharwat, Tektonidou, Maria, Dagostin, Marília A, Opinc, Aleksandra, Sebastiani, Gian Domenico, Giacomelli, Roberto, Giudice, Emanuela Del, Olivieri, Alma Nunzia, Tufan, Abdurrahman, Kardas, Riza Kan, Nuzzolese, Rossana, Cardinale, Fabio, Więsik-Szewczyk, Ewa, Veronica, Parretti, Tarsia, Maria, Iannone, Florenzo, Della Casa, Francesca, Fabiani, Claudia, Frediani, Bruno, Balistreri, Alberto, Rigante, Donato, Cantarini, Luca, Sota J., Vitale A., Lopalco G., Pereira R.M.R., Giordano H.F., Antonelli I.P.B., Makowska J., Brzezinska O., Lewandowska-Polak A., Ruscitti P., Cipriani P., Cola I.D., Govoni M., Ruffili F., Sfikakis P.P., Laskari K., Ragab G., Hussein M.A., Gentileschi S., Gaggiano C., La Torre F., Maier A., Emmi G., Marino A., Ciccia F., Sfriso P., Maggio M.C., Bartoloni E., Lomater C., Hegazy M.T., Tektonidou M., Dagostin M.A., Opinc A., Sebastiani G.D., Giacomelli R., Giudice E.D., Olivieri A.N., Tufan A., Kardas R.K., Nuzzolese R., Cardinale F., Wiesik-Szewczyk E., Veronica P., Tarsia M., Iannone F., Della Casa F., Fabiani C., Frediani B., Balistreri A., Rigante D., and Cantarini L.
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Registrie ,Adult ,Male ,Settore MED/16 - REUMATOLOGIA ,Interleukin-6 ,Innovative biotechnologies ,Tocilizumab ,Adult-onset Still's disease ,Antibodies, Monoclonal, Humanized ,Personalized medicine ,Settore MED/38 - Pediatria Generale E Specialistica ,Anesthesiology and Pain Medicine ,Rheumatology ,Innovative biotechnologie ,Still's disease ,Humans ,Female ,Registries ,Immunotherapy ,Still's Disease, Adult-Onset ,Human - Abstract
© 2022 Elsevier Inc.Background/objectives: Long-term efficacy and safety of tocilizumab (TCZ) in adult-onset Still's disease (AOSD) mostly derive from small case series. Herein we report a registry-based study investigating TCZ efficacy and safety in a cohort of patients with AOSD evaluated by clinical and serum inflammatory markers as well as drug retention rate analysis. Methods: This is an international multicentre study analyzing data from patients with AOSD regularly enrolled in the AIDA registry. TCZ efficacy was evaluated between baseline and last follow-up assessment in terms of changes in the Pouchot score and laboratory findings. Drug-retention rate was estimated by the Kaplan-Meier method, while Cox-regression analysis was employed to detect potential predictive factors of treatment withdrawal. Results: Data from 31 patients (15 men, 16 women) refractory to the conventional therapies and treated with TCZ were extracted from the AIDA registry. Mean ± SD time of treatment duration with TCZ was 24.32 ± 20.57 months. Median (IRQ) Pouchot score significantly decreased throughout the study period (p=0.001) with a significant difference between baseline [2.00 (4.00)] and 6 month-follow-up [0.00 (0.00)] (p=0.003) and between baseline and last follow-up assessment [0.00 (0.00)] (p=0.032), while no differences were observed between 6 month-evaluation and last follow-up assessment (p=0.823). Similarly, laboratory parameters significantly decreased from baseline to the last follow-up visit. With regard to drug survival, cumulative TCZ retention rate at 12-, 24-, and 36-month follow-up visit were 83.1%, 71.7% and 63.7%, respectively, without significant differences between biologic naïve patients and those previously treated with other biologics (p=0.329). Likewise, no significant differences were observed between chronic articular course of AOSD and other types of disease course (p=0.938) or between patients co-administered with conventional immunosuppressants and patients receiving TCZ as monotherapy (p=0.778). Cox-regression analysis identified no variable associated with a higher hazard of treatment withdrawal. Treatment was discontinued in 9 patients due to long-term remission (n=4), adverse events (n=2), loss of efficacy (n=1), non-medical reason (n=1) and unspecified cause (n=1). Mean glucocorticosteroids daily dose significantly decreased from baseline (18.36 ± 24.72 mg) to the last follow-up assessment (4.02 ± 4.99 mg, p=0.003). Conclusions: TCZ allows control of disease activity as well as normalization of serum inflammatory markers in both systemic and chronic articular form of AOSD. Additionally, TCZ displays an excellent drug retention rate while minimizing the risk of long-term exposure to corticosteroids.
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- 2022
374. Inflammatory Bowel Diseases and Coexisting Spondyloarthritis: A Neglected and too Often Under-Reported Association by Radiologists. A Multicenter Study by Italian Research Group of Imaging in Rheumatology
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Maria Antonietta Mazzei, Bruno Frediani, Alfonso Reginelli, Antonio Barile, Antonio Marchesoni, Alessia Vinci, Andrea Giovagnoni, Luca Brunese, Nicola Maggialetti, Giulia Sadotti, Luca Cantarini, Francesco Gentili, Marina Carotti, Giuseppe Capodieci, Giovanna Vacca, Francesca Interlicchia, Nunzia Di Meglio, Ubaldo Plastina Romeo, Giuseppe Lo Re, Rita Lo Scalzo, Luca Volterrani, Susanna Guerrini, Ernesto La Paglia, Federico Bruno, Mazzei, M. A., Gentili, F., Guerrini, S., Di Meglio, N., Lo Re, G., Carotti, M., Interlicchia, F., Reginelli, A., Barile, A., Sadotti, G., Romeo, U. P., La Paglia, E., Maggialetti, N., Lo Scalzo, R., Vinci, A., Capodieci, G., Vacca, G., Bruno, F., Cantarini, L., Frediani, B., Marchesoni, A., Giovagnoni, A., Volterrani, L., and Brunese, L.
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Crohn’s disease ,medicine.medical_specialty ,RC799-869 ,CT ,CT enterography ,MR enterography ,MRI ,Sacroiliitis ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,030203 arthritis & rheumatology ,Sacroiliac joint ,Crohn's disease ,Hepatology ,business.industry ,Gastroenterology ,Inflammatory Bowel Diseases ,Diseases of the digestive system. Gastroenterology ,medicine.disease ,Rheumatology ,medicine.anatomical_structure ,Multicenter study ,Radiological weapon ,Radiology ,business ,Rheumatism - Abstract
Purpose: The purpose of this study was to evaluate the prevalence and the underreporting rate of sacroiliitis (SI) in a large cohort of patients with biopsy-proved Crohn&rsquo, s disease (CD) who underwent magnetic resonance enterography (MRE) or computed tomography enterography (CTE). Materials and Methods: Patients with CD were recruited from eight Italian health centers in the period from January 2013 to December 2017. Disease activity was recorded according to the CD activity index (CDAI). The scans were read by two blinded readers who defined the presence of SI according to Assessment of SpondyloArthritis International Society (ASAS) classifications and European League Against Rheumatism (EULAR) recommendations. Moreover, SI was scored using a simplified Spondyloarthritis Research Consortium of Canada (SPARCC) scoring system. Results: Interobserver agreement in diagnosing SI on imaging was good (K = 0.72&ndash, 0.83). SI was diagnosed in 129 (14.4%, 54 men, 75 women) out of 894 patients, however, sacroiliac joint (SIJ) abnormalities were not mentioned in the radiological reports of 112 patients (86%). Fifty (38.7%) out of 129 patients also underwent a subsequent SIJ evaluation through a dedicated MRI protocol to confirm SI. SI was found in a higher percentage of patients with &ldquo, active&rdquo, than &ldquo, inactive&rdquo, CD (18% vs. 4%). Conclusion: This study confirms the feasibility of CTE and MRE for the screening of SI in CD patients, however, it also underlines the remarkable problem concerning the underreporting of this entity in radiological practice.
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- 2020
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375. Role of Colchicine Treatment in Tumor Necrosis Factor Receptor Associated Periodic Syndrome (TRAPS): Real-Life Data from the AIDA Network
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Bruno Frediani, Laura Obici, Alessandra Renieri, Jurgen Sota, Valeria Caggiano, Francesco Licciardi, José Hernández-Rodríguez, Roberto Giacomelli, Piero Ruscitti, Antonio Vitale, Nicola Ricco, Lorenzo Dagna, Carlo Salvarani, Maria Cristina Maggio, Davide Montin, Giacomo Emmi, Alessandra Soriano, Marco Cattalini, Luca Cantarini, Ombretta Viapiana, Vittoria Lamacchia, Francesco Caso, Raffaele Manna, Antonella Insalaco, Vitale, Antonio, Sota, Jurgen, Obici, Laura, Ricco, Nicola, Maggio, Maria Cristina, Cattalini, Marco, Ruscitti, Piero, Caso, Francesco, Manna, Raffaele, Viapiana, Ombretta, Caggiano, Valeria, Emmi, Giacomo, Insalaco, Antonella, Montin, Davide, Licciardi, Francesco, Soriano, Alessandra, Dagna, Lorenzo, Salvarani, Carlo, Lamacchia, Vittoria, Hernández-Rodríguez, José, Giacomelli, Roberto, Frediani, Bruno, Renieri, Alessandra, Cantarini, Luca, Vitale, A., Sota, J., Obici, L., Ricco, N., Maggio, M. C., Cattalini, M., Ruscitti, P., Caso, F., Manna, R., Viapiana, O., Caggiano, V., Emmi, G., Insalaco, A., Montin, D., Licciardi, F., Soriano, A., Dagna, L., Salvarani, C., Lamacchia, V., Hernandez-Rodriguez, J., Giacomelli, R., Frediani, B., Renieri, A., and Cantarini, L.
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Male ,0301 basic medicine ,Eye Diseases ,TRAPS,Colchicine,AIDA Network ,Gene mutation ,Gastroenterology ,Receptors, Tumor Necrosis Factor ,chemistry.chemical_compound ,Settore MED/38 - Pediatria Generale E Specialistica ,0302 clinical medicine ,Receptors ,Pathology ,RB1-214 ,Colchicine ,Age of Onset ,Young adult ,Child ,Amyloidosis ,Syndrome ,Middle Aged ,Colchicine, tumor necrosis factor, TRAPS ,Inflamació ,Penetrance ,Phenotype ,Child, Preschool ,Female ,Joint Diseases ,Research Article ,Adult ,Risk ,medicine.medical_specialty ,Adolescent ,Fever ,Article Subject ,Immunology ,Exanthema ,Humans ,Mutation ,Myalgia ,Retrospective Studies ,Young Adult ,Lower risk ,03 medical and health sciences ,Internal medicine ,medicine ,Preschool ,Inflammation ,030203 arthritis & rheumatology ,business.industry ,TRAPS ,Retrospective cohort study ,Cell Biology ,medicine.disease ,030104 developmental biology ,chemistry ,Age of onset ,Tumor Necrosis Factor ,business - Abstract
Objective. To analyze the potential role of colchicine monotherapy in patients with tumor necrosis factor receptor associated periodic syndrome (TRAPS) in terms of control of clinical and laboratory manifestations. Methods. Patients with TRAPS treated with colchicine monotherapy were retrospectively enrolled; demographic, clinical and therapeutic data were collected and statistically analysed after having clustered patients according to different times at disease onset, penetrance of mutations, dosage of colchicine, and different disease manifestations. Results. 24 patients (14 males; 15 with pediatric disease onset) treated with colchicine monotherapy were enrolled. Colchicine resulted in a complete response in 3 (12.5%) cases, partial response in 14 (58.3%) patients, and lack of response in 7 (29.2%) patients. There were not significant differences in colchicine response between pediatric and adult disease onset (p=0.42), between low- and high-penetrance mutations (p=0.62), and according to different dosages (p=0.66). No significant differences were identified in the frequency of specific disease manifestations between patients experiencing any response to colchicine and patients with lack of response. Conclusions. Colchicine monotherapy is useful in a low percentage of TRAPS patients; nevertheless, it could be attempted in patients with milder phenotypes and at a lower risk of developing reactive amyloidosis.
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- 2020
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376. An explainable model of host genetic interactions linked to COVID-19 severity
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Onoja, Anthony, Picchiotti, Nicola, Fallerini, Chiara, Baldassarri, Margherita, Fava, Francesca, Colombo, Francesca, Chiaromonte, Francesca, Renieri, Alessandra, Furini, Simone, Raimondi, Francesco GEN-COVID Multicenter Study: Francesca Mari, Sergio, Daga, Elisa, Benetti, Mirella, Bruttini, Maria, Palmieri, Susanna, Croci, Sara, Amitrano, Ilaria, Meloni, Elisa, Frullanti, Gabriella, Doddato, Mirjam, Lista, Giada, Beligni, Floriana, Valentino, Kristina, Zguro, Rossella, Tita, Annarita, Giliberti, Maria Antonietta Mencarelli, Caterina Lo Rizzo, Anna Maria Pinto, Francesca, Ariani, Laura Di Sarno, Francesca, Montagnani, Mario, Tumbarello, Ilaria, Rancan, Massimiliano, Fabbiani, Barbara, Rossetti, Laura, Bergantini, Miriana, D'Alessandro, Paolo, Cameli, David, Bennett, Federico, Anedda, Simona, Marcantonio, Sabino, Scolletta, Federico, Franchi, Maria Antonietta Mazzei, Susanna, Guerrini, Edoardo, Conticini, Luca, Cantarini, Bruno, Frediani, Danilo, Tacconi, Chiara Spertilli Raffaelli, Marco, Feri, Alice, Donati, Raffaele, Scala, Luca, Guidelli, Genni, Spargi, Marta, Corridi, Cesira, Nencioni, Leonardo, Croci, Gian Piero Caldarelli, Davide, Romani, Paolo, Piacentini, Maria, Bandini, Elena, Desanctis, Silvia, Cappelli, Anna, Canaccini, Agnese, Verzuri, Valentina, Anemoli, Manola, Pisani, Agostino, Ognibene, Alessandro, Pancrazzi, Maria, Lorubbio, Massimo, Vaghi, Antonella D'Arminio Monforte, Federica Gaia Miraglia, Raffaele, Bruno, Marco, Vecchia, Massimo, Girardis, Sophie, Venturelli, Stefano, Busani, Andrea, Cossarizza, Andrea, Antinori, Alessandra, Vergori, Arianna, Emiliozzi, Stefano, Rusconi, Matteo, Siano, Arianna, Gabrieli, Agostino, Riva, Daniela, Francisci, Elisabetta, Schiaroli, Francesco, Paciosi, Andrea, Tommasi, Umberto, Zuccon, Lucia, Vietri, Pier Giorgio Scotton, Francesca, Andretta, Sandro, Panese, Stefano, Baratti, Renzo, Scaggiante, Francesca, Gatti, Saverio Giuseppe Parisi, Francesco, Castelli, Eugenia, Quiros-Roldan, Melania Degli Antoni, Isabella, Zanella, Matteo Della Monica, Carmelo, Piscopo, Mario, Capasso, Roberta, Russo, Immacolata, Andolfo, Achille, Iolascon, Giuseppe, Fiorentino, Massimo, Carella, Marco, Castori, Filippo, Aucella, Pamela, Raggi, Rita, Perna, Matteo, Bassetti, Antonio Di Biagio, Maurizio, Sanguinetti, Luca, Masucci, Alessandra, Guarnaccia, Serafina, Valente, Oreste De Vivo, Elena, Bargagli, Marco, Mandalà, Alessia, Giorli, Lorenzo, Salerni, Patrizia, Zucchi, Pierpaolo, Parravicini, Elisabetta, Menatti, Tullio, Trotta, Ferdinando, Giannattasio, Gabriella, Coiro, Fabio, Lena, Gianluca, Lacerenza, Domenico, A Coviello, Cristina, Mussini, Enrico, Martinelli, Luisa, Tavecchia, Mary Ann Belli, Lia, Crotti, Gianfranco, Parati, Maurizio, Sanarico, Filippo, Biscarini, Alessandra, Stella, Marco, Rizzi, Franco, Maggiolo, Diego, Ripamonti, Claudia, Suardi, Tiziana, Bachetti, Maria Teresa La Rovere, Simona, Sarzi-Braga, Maurizio, Bussotti, Katia, Capitani, Simona, Dei, Sabrina, Ravaglia, Rosangela, Artuso, Elena, Andreucci, Giulia, Gori, Angelica, Pagliazzi, Erika, Fiorentini, Antonio, Perrella, Francesco, Bianchi, Paola, Bergomi, Emanuele, Catena, Riccardo, Colombo, Sauro, Luchi, Giovanna, Morelli, Paola, Petrocelli, Sarah, Iacopini, Sara, Modica, Silvia, Baroni, Francesco Vladimiro Segala, Francesco, Menichetti, Marco, Falcone, Giusy, Tiseo, Chiara, Barbieri, Tommaso, Matucci, Grassi, Davide, Ferri, Claudio, Marinangeli, Franco, Brancati, Francesco, Antonella, Vincenti, Valentina, Borgo, Lombardi, Stefania, Mirco, Lenzi, Massimo Antonio Di Pietro, Francesca, Vichi, Benedetta, Romanin, Letizia, Attala, Cecilia, Costa, Andrea, Gabbuti, Roberto, Menè, Marta, Colaneri, Patrizia, Casprini, Giuseppe, Merla, Gabriella Maria Squeo, Marcello, Maffezzoni, Stefania, Mantovani, Mario, U Mondelli, Serena, Ludovisi, Onoja, Anthony, Picchiotti, Nicola, Fallerini, Chiara, Baldassarri, Margherita, Fava, Francesca, nbsp, Multicenter Study, GEN-COVID, Colombo, Francesca, Chiaromonte, Francesca, Renieri, Alessandra, Furini, Simone, Raimondi, Francesco, Anthony, O, Nicola, P, Chiara, F, Margherita, B, Francesca, F, Francesca, C, Alessandra, R, Simone, F, Francesco, R, Mari, F, Daga, S, Benetti, E, Bruttini, M, Palmieri, M, Croci, S, Amitrano, S, Meloni, I, Frullanti, E, Doddato, G, Lista, M, Beligni, G, Valentino, F, Zguro, K, Tita, R, Giliberti, A, Antonietta Mencarelli, M, Lo Rizzo, C, Maria Pinto, A, Ariani, F, Di Sarno, L, Montagnani, F, Tumbarello, M, Rancan, I, Fabbiani, M, Rossetti, B, Bergantini, L, D’Alessandro, M, Cameli, P, Bennett, D, Anedda, F, Marcantonio, S, Scolletta, S, Franchi, F, Antonietta Mazzei, M, Guerrini, S, Conticini, E, Cantarini, L, Frediani, B, Tacconi, D, Spertilli Raffaelli, C, Feri, M, Donati, A, Scala, R, Guidelli, L, Spargi, G, Corridi, M, Nencioni, C, Croci, L, Piero Caldarelli, G, Romani, D, Piacentini, P, Bandini, M, Desanctis, E, Cappelli, S, Canaccini, A, Verzuri, A, Anemoli, V, Pisani, M, Ognibene, A, Pancrazzi, A, Lorubbio, M, Vaghi, M, D’Arminio Monforte, A, Gaia Miraglia, F, Bruno, R, Vecchia, M, Girardis, M, Venturelli, S, Busani, S, Cossarizza, A, Antinori, A, Vergori, A, Emiliozzi, A, Rusconi, S, Siano, M, Gabrieli, A, Riva, A, Francisci, D, Schiaroli, E, Paciosi, F, Tommasi, A, Zuccon, U, Vietri, L, Giorgio Scotton, P, Andretta, F, Panese, S, Baratti, S, Scaggiante, R, Gatti, F, Giuseppe Parisi, S, Castelli, F, Quiros-Roldan, E, Degli Antoni, M, Zanella, I, Della Monica, M, Piscopo, C, Capasso, M, Russo, R, Andolfo, I, Iolascon, A, Fiorentino, G, Carella, M, Castori, M, Aucella, F, Raggi, P, Perna, R, Bassetti, M, Di Biagio, A, Sanguinetti, M, Masucci, L, Guarnaccia, A, Valente, S, De Vivo, O, Bargagli, E, Mandalà, M, Giorli, A, Salerni, L, Zucchi, P, Parravicini, P, Menatti, E, Trotta, T, Giannattasio, F, Coiro, G, Lena, F, Lacerenza, G, Coviello, D, Mussini, C, Martinelli, E, Tavecchia, L, Ann Belli, M, Crotti, L, Parati, G, Sanarico, M, Biscarini, F, Stella, A, Rizzi, M, Maggiolo, F, Ripamonti, D, Suardi, C, Bachetti, T, Teresa La Rovere, M, Sarzi-Braga, S, Bussotti, M, Capitani, K, Dei, S, Ravaglia, S, Artuso, R, Andreucci, E, Gori, G, Pagliazzi, A, Fiorentini, E, Perrella, A, Bianchi, F, Bergomi, P, Catena, E, Colombo, R, Luchi, S, Morelli, G, Petrocelli, P, Iacopini, S, Modica, S, Baroni, S, Vladimiro Segala, F, Menichetti, F, Falcone, M, Tiseo, G, Barbieri, C, Matucci, T, Grassi, D, Ferri, C, Marinangeli, F, Brancati, F, Vincenti, A, Borgo, V, Lombardi, S, Lenzi, M, Antonio Di Pietro, M, Vichi, F, Romanin, B, Attala, L, Costa, C, Gabbuti, A, Menè, R, Colaneri, M, Casprini, P, Merla, G, Maria Squeo, G, Maffezzoni, M, Mantovani, S, Mondelli &, M, and Ludovisi, S
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Genetics ,Coronavirus disease 2019 (COVID-19) ,Host (biology) ,COVID-19 ,Medicine (miscellaneous) ,Settore BIO/11 - Biologia Molecolare ,Biology ,Settore MED/07 - MICROBIOLOGIA E MICROBIOLOGIA CLINICA ,Whole Exome Sequencing ,General Biochemistry, Genetics and Molecular Biology ,machine learning ,Phenotype ,Exome Sequencing ,Humans ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,General Agricultural and Biological Sciences ,COVID ,Human - Abstract
We employed a multifaceted computational strategy to identify the genetic factors contributing to increased risk of severe COVID-19 infection from a Whole Exome Sequencing (WES) dataset of a cohort of 2000 Italian patients. We coupled a stratified k-fold screening, to rank variants more associated with severity, with training of multiple supervised classifiers, to predict severity on the basis of screened features. Feature importance analysis from tree-based models allowed to identify a handful of 16 variants with highest support which, together with age and gender covariates, were found to be most predictive of COVID-19 severity. When tested on a follow-up cohort, our ensemble of models predicted severity with good accuracy (ACC=81.88%; ROC_AUC=96%; MCC=61.55%). Principal Component Analysis (PCA) and clustering of patients on important variants orthogonally identified two groups of individuals with a higher fraction of severe cases. Our model recapitulated a vast literature of emerging molecular mechanisms and genetic factors linked to COVID-19 response and extends previous landmark Genome Wide Association Studies (GWAS). It revealed a network of interplaying genetic signatures converging on established immune system and inflammatory processes linked to viral infection response, such as JAK-STAT, Cytokine, Interleukin, and C-type lectin receptor signaling. It also identified additional processes cross-talking with immune pathways, such as GPCR signalling, which might offer additional opportunities for therapeutic intervention and patient stratification. Publicly available PheWAS datasets revealed that several variants were significantly associated with phenotypic traits such as “Respiratory or thoracic disease”, confirming their link with COVID-19 severity outcome. Taken together, our analysis suggests that curated genetic information can be effectively integrated along with other patient clinical covariates to forecast COVID-19 disease severity and dissect the underlying host genetic mechanisms for personalized medicine treatments.
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- 2022
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377. Development and implementation of the AIDA International Registry for patients with Periodic Fever, Aphthous stomatitis, Pharyngitis, and cervical Adenitis syndrome
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Francesca Della Casa, Antonio Vitale, Marco Cattalini, Francesco La Torre, Giovanna Capozio, Emanuela Del Giudice, Maria Cristina Maggio, Giovanni Conti, Maria Alessio, Benson Ogunjimi, Gaafar Ragab, Giacomo Emmi, Emma Aragona, Teresa Giani, Giuseppe Lopalco, Paola Parronchi, Farhad Shahram, Elena Verrecchia, Francesca Ricci, Fabio Cardinale, Silvia Di Noi, Rossana Nuzzolese, Riccardo Lubrano, Serena Patroniti, Roberta Naddei, Vito Sabato, Mohamed A. Hussein, Laura Dotta, Violetta Mastrorilli, Stefano Gentileschi, Abdurrahman Tufan, Valeria Caggiano, Mohamed Tharwat Hegazy, Jurgen Sota, Ibrahim A. Almaghlouth, Amr Ibrahim, Ewa Wiȩsik-Szewczyk, Burcugul Ozkiziltas, Salvatore Grosso, Micol Frassi, Maria Tarsia, Rosa Maria R. Pereira, Maged Taymour, Carla Gaggiano, Sergio Colella, Claudia Fabiani, Maria Morrone, Piero Ruscitti, Bruno Frediani, Veronica Spedicato, Henrique A. Mayrink Giardini, Alberto Balistreri, Donato Rigante, Luca Cantarini, Della Casa, F, Vitale, A, Cattalini, M, La Torre, F, Capozio, G, Del Giudice, E, Maggio, Mc, Conti, G, Alessio, M, Ogunjimi, B, Ragab, G, Emmi, G, Aragona, E, Giani, T, Lopalco, G, Parronchi, P, Shahram, F, Verrecchia, E, Ricci, F, Cardinale, F, Di Noi, S, Nuzzolese, R, Lubrano, R, Patroniti, S, Naddei, R, Sabato, V, Hussein, Ma, Dotta, L, Mastrorilli, V, Gentileschi, S, Tufan, A, Caggiano, V, Hegazy, Mt, Sota, J, Almaghlouth, Ia, Ibrahim, A, Wiȩsik-Szewczyk, E, Ozkiziltas, B, Grosso, S, Frassi, M, Tarsia, M, Pereira, Rmr, Taymour, M, Gaggiano, C, Colella, S, Fabiani, C, Morrone, M, Ruscitti, P, Frediani, B, Spedicato, V, Giardini, Ham, Balistreri, A, Rigante, D, Cantarini, L., Della Casa, Francesca, Vitale, Antonio, Cattalini, Marco, La Torre, Francesco, Capozio, Giovanna, Del Giudice, Emanuela, Maggio, Maria Cristina, Conti, Giovanni, Alessio, Maria, Ogunjimi, Benson, Ragab, Gaafar, Emmi, Giacomo, Aragona, Emma, Giani, Teresa, Lopalco, Giuseppe, Parronchi, Paola, Shahram, Farhad, Verrecchia, Elena, Ricci, Francesca, Cardinale, Fabio, Di Noi, Silvia, Nuzzolese, Rossana, Lubrano, Riccardo, Patroniti, Serena, Naddei, Roberta, Sabato, Vito, Hussein, Mohamed A, Dotta, Laura, Mastrorilli, Violetta, Gentileschi, Stefano, Tufan, Abdurrahman, Caggiano, Valeria, Hegazy, Mohamed Tharwat, Sota, Jurgen, Almaghlouth, Ibrahim A, Ibrahim, Amr, Wiȩsik-Szewczyk, Ewa, Ozkiziltas, Burcugul, Grosso, Salvatore, Frassi, Micol, Tarsia, Maria, Pereira, Rosa Maria R, Taymour, Maged, Gaggiano, Carla, Colella, Sergio, Fabiani, Claudia, Morrone, Maria, Ruscitti, Piero, Frediani, Bruno, Spedicato, Veronica, Giardini, Henrique A Mayrink, Balistreri, Alberto, Rigante, Donato, and Cantarini, Luca
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Registry ,rare disease ,PFAPA syndrome ,autoinflammatory diseases ,international registry ,personalized medicine ,precision medicine ,Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA ,autoinflammatory disease ,Pediatrics, Perinatology and Child Health ,Human medicine - Abstract
ObjectiveAim of this paper is to illustrate the methodology, design, and development of the AutoInflammatory Disease Alliance (AIDA) International Registry dedicated to patients with the Periodic Fever, Aphthous stomatitis, Pharyngitis, and cervical Adenitis (PFAPA) syndrome.MethodsThis is a physician-driven, non-population- and electronic-based registry proposed to gather real-world demographics, clinical, laboratory, instrumental and socioeconomic data from PFAPA patients. Data recruitment is realized through the on-line Research Electronic Data Capture (REDCap) tool. This registry is thought to collect standardized information for clinical research leading to solid real-life evidence. The international scope and the flexibility of the registry will facilitate the realization of cutting-edge study projects through the constant updating of variables and the possible merging and transfer of data between current and future PFAPA registries.ResultsA total of 112 centers have already been involved from 23 countries and 4 continents starting from August 24th, 2021, to April 6th, 2022. In total 56/112 have already obtained the formal approval from their local Ethics Committees. The platform counts 321 users (113 principal investigators, 203 site investigators, two lead investigators, and three data managers). The registry collects retrospective and prospective data using 3,856 fields organized into 25 instruments, including PFAPA patient's demographics, medical histories, symptoms, triggers/risk factors, therapies, and impact on the healthcare systems.ConclusionsThe development of the AIDA International Registry for PFAPA patients will enable the on-line collection of standardized data prompting real-life studies through the connection of worldwide groups of physicians and researchers. This project can be found on https://clinicaltrials.gov NCT 05200715.
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- 2022
378. Development and implementation of the AIDA international registry for patients with Still's disease
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Antonio Vitale, Francesca Della Casa, Giuseppe Lopalco, Rosa Maria Pereira, Piero Ruscitti, Roberto Giacomelli, Gaafar Ragab, Francesco La Torre, Elena Bartoloni, Emanuela Del Giudice, Claudia Lomater, Giacomo Emmi, Marcello Govoni, Maria Cristina Maggio, Armin Maier, Joanna Makowska, Benson Ogunjimi, Petros P. Sfikakis, Paolo Sfriso, Carla Gaggiano, Florenzo Iannone, Marília A. Dagostin, Ilenia Di Cola, Luca Navarini, Ayman Abdelmonem Ahmed Mahmoud, Fabio Cardinale, Ilenia Riccucci, Maria Pia Paroli, Elena Maria Marucco, Irene Mattioli, Jurgen Sota, Anna Abbruzzese, Isabele P. B. Antonelli, Paola Cipriani, Abdurrahman Tufan, Claudia Fabiani, Mustafa Mahmoud Ramadan, Marco Cattalini, Riza Can Kardas, Gian Domenico Sebastiani, Henrique A. Mayrink Giardini, José Hernández-Rodríguez, Violetta Mastrorilli, Ewa Więsik-Szewczyk, Micol Frassi, Valeria Caggiano, Salvatore Telesca, Heitor F. Giordano, Emmanuele Guadalupi, Teresa Giani, Alessandra Renieri, Sergio Colella, Giulia Cataldi, Martina Gentile, Alessandra Fabbiani, Ibrahim A. Al-Maghlouth, Bruno Frediani, Alberto Balistreri, Donato Rigante, Luca Cantarini, Autoinflammatory Diseases Alliance (AIDA) Network, Vitale A., Della Casa F., Lopalco G., Pereira R.M., Ruscitti P., Giacomelli R., Ragab G., La Torre F., Bartoloni E., Del Giudice E., Lomater C., Emmi G., Govoni M., Maggio M.C., Maier A., Makowska J., Ogunjimi B., Sfikakis P.P., Sfriso P., Gaggiano C., Iannone F., Dagostin M.A., Di Cola I., Navarini L., Ahmed Mahmoud A.A., Cardinale F., Riccucci I., Paroli M.P., Marucco E.M., Mattioli I., Sota J., Abbruzzese A., Antonelli I.P.B., Cipriani P., Tufan A., Fabiani C., Ramadan M.M., Cattalini M., Kardas R.C., Sebastiani G.D., Giardini H.A.M., Hernandez-Rodriguez J., Mastrorilli V., Wiesik-Szewczyk E., Frassi M., Caggiano V., Telesca S., Giordano H.F., Guadalupi E., Giani T., Renieri A., Colella S., Cataldi G., Gentile M., Fabbiani A., Al-Maghlouth I.A., Frediani B., Balistreri A., Rigante D., and Cantarini L.
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Registry ,Settore MED/16 - REUMATOLOGIA ,research ,treatment ,precision medicine ,rare diseases ,General Medicine ,personalized medicine ,autoinflammatory diseases ,Settore MED/38 - Pediatria Generale E Specialistica ,autoinflammatory diseases, personalized medicine, precision medicine, rare diseases, research treatment ,Still's disease ,Human medicine - Abstract
ObjectiveAim of this paper is to present the design, construction, and modalities of dissemination of the AutoInflammatory Disease Alliance (AIDA) International Registry for patients with systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still's disease (AOSD), which are the pediatric and adult forms of the same autoinflammatory disorder.MethodsThis Registry is a clinical, physician-driven, population- and electronic-based instrument implemented for the retrospective and prospective collection of real-world data. The collection of data is based on the Research Electronic Data Capture (REDCap) tool and is intended to obtain evidence drawn from routine patients' management. The collection of standardized data is thought to bring knowledge about real-life clinical research and potentially communicate with other existing and future Registries dedicated to Still's disease. Moreover, it has been conceived to be flexible enough to easily change according to future scientific acquisitions.ResultsStarting from June 30th to February 7th, 2022, 110 Centers from 23 Countries in 4 continents have been involved. Fifty-four of these have already obtained the approval from their local Ethics Committees. Currently, the platform counts 290 users (111 Principal Investigators, 175 Site Investigators, 2 Lead Investigators, and 2 data managers). The Registry collects baseline and follow-up data using 4449 fields organized into 14 instruments, including patient's demographics, history, clinical manifestations and symptoms, trigger/risk factors, therapies and healthcare access.ConclusionsThis international Registry for patients with Still's disease will allow a robust clinical research through collection of standardized data, international consultation, dissemination of knowledge, and implementation of observational studies based on wide cohorts of patients followed-up for very long periods. Solid evidence drawn from “real-life” data represents the ultimate goal of this Registry, which has been implemented to significantly improve the overall management of patients with Still's disease. NCT 05200715 available at https://clinicaltrials.gov/.
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- 2022
379. Development and Implementation of the AIDA International Registry for Patients With VEXAS Syndrome
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Antonio Vitale, Valeria Caggiano, Francesca Della Casa, José Hernández-Rodríguez, Micol Frassi, Sara Monti, Abdurrahman Tufan, Salvatore Telesca, Edoardo Conticini, Gaafar Ragab, Giuseppe Lopalco, Ibrahim Almaghlouth, Rosa Maria R. Pereira, Derya Yildirim, Marco Cattalini, Achille Marino, Teresa Giani, Francesco La Torre, Piero Ruscitti, Emma Aragona, Ewa Wiesik-Szewczyk, Emanuela Del Giudice, Petros P. Sfikakis, Marcello Govoni, Giacomo Emmi, Maria Cristina Maggio, Roberto Giacomelli, Francesco Ciccia, Giovanni Conti, Djouher Ait-Idir, Claudia Lomater, Vito Sabato, Matteo Piga, Ali Sahin, Daniela Opris-Belinski, Ruxandra Ionescu, Elena Bartoloni, Franco Franceschini, Paola Parronchi, Amato de Paulis, Gerard Espinosa, Armin Maier, Gian Domenico Sebastiani, Antonella Insalaco, Farhad Shahram, Paolo Sfriso, Francesca Minoia, Maria Alessio, Joanna Makowska, Gülen Hatemi, Nurullah Akkoç, Francesca Li Gobbi, Antonio Gidaro, Alma Nunzia Olivieri, Sulaiman M. Al-Mayouf, Sükran Erten, Stefano Gentileschi, Ibrahim Vasi, Maria Tarsia, Ayman Abdel-Monem Ahmed Mahmoud, Bruno Frediani, Musa Fares Alzahrani, Ahmed Hatem Laymouna, Francesca Ricci, Fabio Cardinale, Karina Jahnz-Rózyk, Gian Marco Tosi, Francesca Crisafulli, Alberto Balistreri, Marília A. Dagostin, Mahmoud Ghanema, Carla Gaggiano, Jurgen Sota, Ilenia Di Cola, Claudia Fabiani, Henrique A. Mayrink Giardini, Alessandra Renieri, Alessandra Fabbiani, Anna Carrer, Monica Bocchia, Federico Caroni, Donato Rigante, Luca Cantarini, Vitale, Antonio, Caggiano, Valeria, Della Casa, Francesca, Hernández-Rodríguez, José, Frassi, Micol, Monti, Sara, Tufan, Abdurrahman, Telesca, Salvatore, Conticini, Edoardo, Ragab, Gaafar, Lopalco, Giuseppe, Almaghlouth, Ibrahim, Pereira, Rosa Maria R, Yildirim, Derya, Cattalini, Marco, Marino, Achille, Giani, Teresa, La Torre, Francesco, Ruscitti, Piero, Aragona, Emma, Wiesik-Szewczyk, Ewa, Del Giudice, Emanuela, Sfikakis, Petros P, Govoni, Marcello, Emmi, Giacomo, Maggio, Maria Cristina, Giacomelli, Roberto, Ciccia, Francesco, Conti, Giovanni, Ait-Idir, Djouher, Lomater, Claudia, Sabato, Vito, Piga, Matteo, Sahin, Ali, Opris-Belinski, Daniela, Ionescu, Ruxandra, Bartoloni, Elena, Franceschini, Franco, Parronchi, Paola, de Paulis, Amato, Espinosa, Gerard, Maier, Armin, Sebastiani, Gian Domenico, Insalaco, Antonella, Shahram, Farhad, Sfriso, Paolo, Minoia, Francesca, Alessio, Maria, Makowska, Joanna, Hatemi, Gülen, Akkoç, Nurullah, Li Gobbi, Francesca, Gidaro, Antonio, Olivieri, Alma Nunzia, Al-Mayouf, Sulaiman M, Erten, Sükran, Gentileschi, Stefano, Vasi, Ibrahim, Tarsia, Maria, Mahmoud, Ayman Abdel-Monem Ahmed, Frediani, Bruno, Fares Alzahrani, Musa, Laymouna, Ahmed Hatem, Ricci, Francesca, Cardinale, Fabio, Jahnz-Rózyk, Karina, Tosi, Gian Marco, Crisafulli, Francesca, Balistreri, Alberto, Dagostin, Marília A, Ghanema, Mahmoud, Gaggiano, Carla, Sota, Jurgen, Di Cola, Ilenia, Fabiani, Claudia, Giardini, Henrique A Mayrink, Renieri, Alessandra, Fabbiani, Alessandra, Carrer, Anna, Bocchia, Monica, Caroni, Federico, Rigante, Donato, Cantarini, Luca, Vitale, A, Caggiano, V, Della Casa, F, Hernández-Rodríguez, J, Frassi, M, Monti, S, Tufan, A, Telesca, S, Conticini, E, Ragab, G, Lopalco, G, Almaghlouth, I, Pereira, Rmr, Yildirim, D, Cattalini, M, Marino, A, Giani, T, La Torre, F, Ruscitti, P, Aragona, E, Wiesik-Szewczyk, E, Del Giudice, E, Sfikakis, Pp, Govoni, M, Emmi, G, Maggio, Mc, Giacomelli, R, Ciccia, F, Conti, G, Ait-Idir, D, Lomater, C, Sabato, V, Piga, M, Sahin, A, Opris-Belinski, D, Ionescu, R, Bartoloni, E, Franceschini, F, Parronchi, P, de Paulis, A, Espinosa, G, Maier, A, Sebastiani, Gd, Insalaco, A, Shahram, F, Sfriso, P, Minoia, F, Alessio, M, Makowska, J, Hatemi, G, Akkoç, N, Li Gobbi, F, Gidaro, A, Olivieri, An, Al-Mayouf, Sm, Erten, S, Gentileschi, S, Vasi, I, Tarsia, M, Mahmoud, Aaa, Frediani, B, Fares Alzahrani, M, Laymouna, Ah, Ricci, F, Cardinale, F, Jahnz-Rózyk, K, Tosi, Gm, Crisafulli, F, Balistreri, A, Dagostin, Ma, Ghanema, M, Gaggiano, C, Sota, J, Di Cola, I, Fabiani, C, Giardini, Ham, Renieri, A, Fabbiani, A, Carrer, A, Bocchia, M, Caroni, F, Rigante, D, and Cantarini, L.
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Registry ,Keywords: autoinflammatory diseases ,clinical management ,precision medicine ,rare diseases ,research ,treatment ,Settore MED/16 - REUMATOLOGIA ,rare disease ,General Medicine ,autoinflammatory diseases ,Settore MED/38 - Pediatria Generale E Specialistica ,autoinflammatory disease ,VEXAS syndrome ,Human medicine - Abstract
ObjectiveThe aim of this paper is to present the AutoInflammatory Disease Alliance (AIDA) international Registry dedicated to Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic (VEXAS) syndrome, describing its design, construction, and modalities of dissemination.MethodsThis Registry is a clinical, physician-driven, population- and electronic-based instrument designed for the retrospective and prospective collection of real-life data. Data gathering is based on the Research Electronic Data Capture (REDCap) tool and is intended to obtain real-world evidence for daily patients' management. The Registry may potentially communicate with other on-line tools dedicated to VEXAS syndrome, thus enhancing international collaboration and data sharing for research purposes. The Registry is practical enough to be easily modified to meet future needs regarding VEXAS syndrome.ResultsTo date (April 22nd, 2022), 113 Centers from 23 Countries in 4 continents have been involved; 324 users (114 Principal Investigators, 205 Site Investigators, 2 Lead Investigators, and 3 data managers) are currently able to access the registry for data entry (or data sharing) and collection. The Registry includes 4,952 fields organized into 18 instruments designed to fully describe patient's details about demographics, clinical manifestations, symptoms, histologic details about skin and bone marrow biopsies and aspirate, laboratory features, complications, comorbidities, therapies, and healthcare access.ConclusionThis international Registry for patients with VEXAS syndrome will allow the achievement of a comprehensive knowledge about this new disease, with the final goal to obtain real-world evidence for daily clinical practice, especially in relation to the comprehension of this disease about the natural history and the possible therapeutic approaches. This Project can be found on https://clinicaltrials.gov NCT05200715.
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- 2022
380. The joint involvement in adult onset Still's disease is characterised by a peculiar magnetic resonance imaging and a specific transcriptomic profile
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Paola Di Benedetto, Piero Ruscitti, Onorina Berardicurti, Federico Bruno, Luca Cantarini, Roberto Giacomelli, Francesco Ursini, Francesco Caso, Raffaele Scarpa, Luca Navarini, Sonia Iafrate, Carlo Masciocchi, Federica Sensini, Antonio Vitale, Bruno Frediani, Paola Cipriani, Antonio Barile, Luisa Costa, Ruscitti P., Barile A., Berardicurti O., Iafrate S., Di Benedetto P., Vitale A., Caso F., Costa L., Bruno F., Ursini F., Navarini L., Sensini F., Scarpa R., Frediani B., Cantarini L., Masciocchi C., Giacomelli R., and Cipriani P.
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Adult ,Male ,0301 basic medicine ,medicine.medical_specialty ,Pathology ,Science ,Arthritis ,Pathogenesis ,Disease ,Article ,03 medical and health sciences ,0302 clinical medicine ,Rheumatology ,Internal medicine ,Synovitis ,medicine ,Humans ,RNA-Seq ,030203 arthritis & rheumatology ,Multidisciplinary ,biology ,medicine.diagnostic_test ,Interleukin-6 ,Tumor Necrosis Factor-alpha ,business.industry ,Synovial Membrane ,Magnetic resonance imaging ,Middle Aged ,medicine.disease ,Magnetic Resonance Imaging ,Ferritin ,030104 developmental biology ,Gene Expression Regulation ,Erythrocyte sedimentation rate ,biology.protein ,Medicine ,AOSD ,Female ,business ,Still's Disease, Adult-Onset ,Interleukin-1 ,Signal Transduction - Abstract
Adult onset Still's disease (AOSD) is a rare systemic autoinflammatory disease, characterised by fever, arthritis, and skin rash, and joint involvement is one of its clinical manifestations. The aims of this work were to assess joint involvement, to describe main patterns of involvement, and associated clinical characteristics. In this work, we aimed at assessing the joint involvement in AOSD by using MRI, to describe main patterns and associated clinical characteristics. In addition, we aimed at assessing the global transcriptomic profile of synovial tissues in AOSD to elucidate possible pathogenic pathways involved. We also evaluated the global transcriptomic profile of synovial tissues to elucidate possible pathogenic pathways involved in the disease. Thus, AOSD patients, who underwent to MRI exam on joints, were assessed to describe patterns of joint involvement and associated clinical characteristics. Some synovial tissues were collected for RNA-sequencing purposes. The most common MRI finding was the presence of synovitis on 60.5%, mainly in peripheral affected joints, with low to intermediate signal intensity on T1-weighted images and intermediate to high signal intensity on T2-fat-saturated weighted and STIR images. Bone oedema and MRI-bone erosions were reported on 34.9% and 25.6% MRI exams, respectively. Patients with MRI-bone erosions showed a higher prevalence of splenomegaly, a more frequent chronic disease course, lower levels of erythrocyte sedimentation rate, and ferritin. In AOSD synovial tissues, a hyper-expression of interleukin (IL)-1, IL-6, and TNF pathways was shown together with ferritin genes. In conclusion, in AOSD patients, the most common MRI-finding was the presence of synovitis, characterised by intermediate to high signal intensity on T2-fat-saturated weighted and STIR images. MRI-bone erosions and bone oedema were also observed. In AOSD synovial tissues, IL-1, IL-6, and TNF pathways together with ferritin genes resulted to be hyper-expressed.
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- 2021
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381. Employing a systematic approach to biobanking and analyzing clinical and genetic data for advancing COVID-19 research
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Daga, Sergio, Fallerini, Chiara, Baldassarri, Margherita, Fava, Francesca, Valentino, Floriana, Doddato, Gabriella, Benetti, Elisa, Furini, Simone, Giliberti, Annarita, Tita, Rossella, Amitrano, Sara, Bruttini, Mirella, Meloni, Ilaria, Pinto, Anna Maria, Raimondi, Francesco, Stella, Alessandra, Biscarini, Filippo, Picchiotti, Nicola, Gori, Marco, Pinoli, Pietro, Ceri, Stefano, Sanarico, Maurizio, Crawley, Francis P, Birolo, Giovanni, Renieri, Alessandra, Mari, Francesca, Frullanti, Elisa, Francesca, Montagnani2, Laura Di Sarno1, 2, Andrea, Tommasi1, 2, 3, Maria, Palmieri1, Susanna, Croci1, Arianna, Emiliozzi2, Massimiliano, Fabbiani14, Barbara, Rossetti14, Giacomo, Zanelli2, Laura, Bergantini15, Miriana, D’Alessandro15, Paolo, Cameli15, David, Bennett15, Federico, Anedda16, Simona, Marcantonio16, Sabino, Scolletta16, Federico, Franchi16, Maria Antonietta Mazzei17, Susanna, Guerrini17, Edoardo, Conticini18, Luca, Cantarini18, Bruno, Frediani18, Danilo, Tacconi19, Chiara, Spertilli19, Marco, Feri20, Alice, Donati20, Raffaele, Scala21, Luca, Guidelli21, Genni, Spargi22, Marta, Corridi22, Cesira, Nencioni23, Leonardo, Croci23, Gian Piero Caldarelli24, Maurizio, Spagnesi25, Paolo, Piacentini25, Maria, Bandini25, Elena, Desanctis25, Silvia, Cappelli25, Anna, Canaccini26, Agnese, Verzuri26, Valentina, Anemoli26, Agostino, Ognibene27, Massimo, Vaghi28, Antonella D’Arminio Monforte29, Esther, Merlini29, Mondelli30, Mario U., Stefania, Mantovani30, Serena, Ludovisi30, Massimo, Girardis32, Sophie, Venturelli32, Marco, Sita32, Andrea, Cossarizza33, Andrea, Antinori34, Alessandra, Vergori34, Stefano, Rusconi35, Matteo, Siano36, Arianna, Gabrieli36, Agostino, Riva35, Daniela, Francisci37, Elisabetta, Schiaroli37, Pier Giorgio Scotton39, Francesca, Andretta39, Sandro, Panese40, Renzo, Scaggiante41, Francesca, Gatti41, Saverio Giuseppe Parisi42, Francesco, Castelli43, Maria Eugenia Quiros-Roldan43, Paola, Magro43, Isabella, Zanella44, Matteo Della Monica45, Carmelo, Piscopo45, Mario, Capasso46, 47, 48, Roberta, Russo46, Immacolata, Andolfo46, Achille Iolascon 46, Giuseppe, Fiorentino, Massimo, Carella, Marco, Castori50, Giuseppe, Merla50, Filippo, Aucella51, Pamela, Raggi52, Carmen, Marciano52, Rita, Perna52, Bassetti, Matteo, DI BIAGIO, Antonio, Maurizio, Sanguinetti55, Luca, Masucci55, Chiara, Gabbi57, Serafina, Valente58, Ilaria, Meloni1, Maria Antonietta Mencarelli3, Caterina Lo Rizzo3, Elena, Bargagli15, Marco, Mandalà59, Alessia, Giorli59, Lorenzo, Salerni59, Patrizia, Zucchi60, Pierpaolo, Parravicini60, Elisabetta, Menatti61, Stefano, Baratti62, Tullio, Trotta63, Ferdinando, Giannattasio63, Gabriella, Coiro63, Fabio, Lena64, Coviello65, Domenico A., Cristina, Mussini66, Giancarlo, Bosio, Sandro, Mancarella68, Luisa, Tavecchia68., University of Siena (University of Siena), ANR-19-P3IA-0002,3IA@cote d'azur,3IA Côte d'Azur(2019), Daga, S., Fallerini, C., Baldassarri, M., Fava, F., Valentino, F., Doddato, G., Benetti, E., Furini, S., Giliberti, A., Tita, R., Amitrano, S., Bruttini, M., Meloni, I., Pinto, A. M., Raimondi, F., Stella, A., Biscarini, F., Picchiotti, N., Gori, M., Pinoli, P., Ceri, S., Sanarico, M., Crawley, F. P., Birolo, G., Montagnani, F., Di Sarno, L., Tommasi, A., Palmieri, M., Croci, S., Emiliozzi, A., Fabbiani, M., Rossetti, B., Zanelli, G., Bergantini, L., D'Alessandro, M., Cameli, P., Bennet, D., Anedda, F., Marcantonio, S., Scolletta, S., Franchi, F., Mazzei, M. A., Guerrini, S., Conticini, E., Cantarini, L., Frediani, B., Tacconi, D., Spertilli, C., Feri, M., Donati, A., Scala, R., Guidelli, L., Spargi, G., Corridi, M., Nencioni, C., Croci, L., Caldarelli, G. P., Spagnesi, M., Piacentini, P., Bandini, M., Desanctis, E., Cappelli, S., Canaccini, A., Verzuri, A., Anemoli, V., Ognibene, A., Vaghi, M., D'Arminio Monforte, A., Merlini, E., Mondelli, M. U., Mantovani, S., Ludovisi, S., Girardis, M., Venturelli, S., Sita, M., Cossarizza, A., Antinori, A., Vergori, A., Rusconi, S., Siano, M., Gabrieli, A., Riva, A., Francisci, D., Schiaroli, E., Scotton, P. G., Andretta, F., Panese, S., Scaggiante, R., Gatti, F., Parisi, S. G., Castelli, F., Quiros-Roldan, M. E., Magro, P., Zanella, I., Della Monica, M., Piscopo, C., Capasso, M., Russo, R., Andolfo, I., Iolascon, A., Fiorentino, G., Carella, M., Castori, M., Merla, G., Aucella, F., Raggi, P., Marciano, C., Perna, R., Bassetti, M., Di Biagio, A., Sanguinetti, M., Masucci, L., Gabbi, C., Valente, S., Mencarelli, M. A., Rizzo, C. L., Bargagli, E., Mandala, M., Giorli, A., Salerni, L., Zucchi, P., Parravicini, P., Menatti, E., Baratti, S., Trotta, T., Giannattasio, F., Coiro, G., Lena, F., Coviello, D. A., Mussini, C., Bosio, G., Mancarella, S., Tavecchia, L., Renieri, A., Mari, F., Frullanti, E., Daga, Sergio, Fallerini, Chiara, Baldassarri, Margherita, Fava, Francesca, Valentino, Floriana, Doddato, Gabriella, Benetti, Elisa, Furini, Simone, Giliberti, Annarita, Tita, Rossella, Amitrano, Sara, Bruttini, Mirella, Meloni, Ilaria, Pinto, Anna Maria, Raimondi, Francesco, Stella, Alessandra, Biscarini, Filippo, Picchiotti, Nicola, Gori, Marco, Pinoli, Pietro, Ceri, Stefano, Sanarico, Maurizio, Crawley, Francis P., Birolo, Giovanni, Renieri, Alessandra, Mari, Francesca, and Frullanti, Elisa
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0301 basic medicine ,Registrie ,Male ,[INFO.INFO-AI]Computer Science [cs]/Artificial Intelligence [cs.AI] ,0302 clinical medicine ,biobanking ,Hyposmia ,Biological Specimen Bank ,Genetics research ,Genetics(clinical) ,genetics ,Registries ,Genetics (clinical) ,Exome sequencing ,Whole blood ,Biological Specimen Banks ,0303 health sciences ,education.field_of_study ,Biobank ,3. Good health ,SNP genotyping ,medicine.anatomical_structure ,Italy ,clinical data ,Female ,medicine.symptom ,Pancreas ,Human ,Adult ,medicine.medical_specialty ,Adolescent ,Population ,Settore BIO/11 - Biologia Molecolare ,COVID-19 ,Humans ,Genetic Predisposition to Disease ,SARS-CoV-2 ,Specimen Handling ,Asymptomatic ,Article ,03 medical and health sciences ,Text mining ,Internal medicine ,medicine ,education ,030304 developmental biology ,business.industry ,snp ,medicine.disease ,030104 developmental biology ,genotyping ,Viral infection ,biobanking, COVID-19, genetics ,business ,Cytokine storm ,030217 neurology & neurosurgery ,exome - Abstract
Within the GEN-COVID Multicenter Study, biospecimens from more than 1,000 SARS-CoV-2-positive individuals have thus far been collected in the GEN-COVID Biobank (GCB). Sample types include whole blood, plasma, serum, leukocytes, and DNA. The GCB links samples to detailed clinical data available in the GEN-COVID Patient Registry (GCPR). It includes hospitalized patients (74.25%), broken down into intubated, treated by CPAP-biPAP, treated with O2 supplementation, and without respiratory support (9.5%, 18.4%, 31.55% and 14.8, respectively); and non-hospitalized subjects (25.75%), either pauci- or asymptomatic. More than 150 clinical patient-level data fields have been collected and binarized for further statistics according to the organs/systems primarily affected by COVID-19: heart, liver, pancreas, kidney, chemosensors, innate or adaptive immunity, and clotting system. Hierarchical Clustering analysis identified five main clinical categories: i) severe multisystemic failure with either thromboembolic or pancreatic variant; ii) cytokine storm type, either severe with liver involvement or moderate; iii) moderate heart type, either with or without liver damage; iv) moderate multisystemic involvement, either with or without liver damage; v) mild, either with or without hyposmia. GCB and GCPR are further linked to the GEN-COVID Genetic Data Repository (GCGDR), which includes data from Whole Exome Sequencing and high-density SNP genotyping. The data are available for sharing through the Network for Italian Genomes, found within the COVID-19 dedicated section. The study objective is to systematize this comprehensive data collection and begin identifying multi-organ involvement in COVID-19, defining genetic parameters for infection susceptibility within the population and mapping genetically COVID-19 severity and clinical complexity among patients.
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- 2021
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382. Biotechnological Agents for Patients With Tumor Necrosis Factor Receptor Associated Periodic Syndrome-Therapeutic Outcome and Predictors of Response: Real-Life Data From the AIDA Network
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Antonio Vitale, Laura Obici, Marco Cattalini, Giuseppe Lopalco, Giampaolo Merlini, Nicola Ricco, Alessandra Soriano, Francesco La Torre, Elena Verrecchia, Antonella Insalaco, Lorenzo Dagna, Masen Abdel Jaber, Davide Montin, Giacomo Emmi, Luisa Ciarcia, Sara Barneschi, Paola Parronchi, Piero Ruscitti, Maria Cristina Maggio, Ombretta Viapiana, Jurgen Sota, Carla Gaggiano, Roberto Giacomelli, Ludovico Luca Sicignano, Raffaele Manna, Alessandra Renieri, Caterina Lo Rizzo, Bruno Frediani, Donato Rigante, Luca Cantarini, Vitale A., Obici L., Cattalini M., Lopalco G., Merlini G., Ricco N., Soriano A., La Torre F., Verrecchia E., Insalaco A., Dagna L., Jaber M.A., Montin D., Emmi G., Ciarcia L., Barneschi S., Parronchi P., Ruscitti P., Maggio M.C., Viapiana O., Sota J., Gaggiano C., Giacomelli R., Sicignano L.L., Manna R., Renieri A., Lo Rizzo C., Frediani B., Rigante D., and Cantarini L.
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0301 basic medicine ,medicine.medical_specialty ,Medicine (General) ,Settore MED/16 - REUMATOLOGIA ,medicine.drug_class ,tumor necrosis factor inhibitors ,biologic therapy, interleukin-1 inhibitors, personalized medicine, tocilizumab, tumor necrosis factor inhibitors, tumor necrosis factor receptor-associated periodic syndrome ,interleukin-1 inhibitors ,Gastroenterology ,03 medical and health sciences ,chemistry.chemical_compound ,tocilizumab ,0302 clinical medicine ,Tocilizumab ,R5-920 ,Internal medicine ,medicine ,biologic therapy ,Adverse effect ,tumor necrosis factor receptor-associated periodic syndrome ,Original Research ,030203 arthritis & rheumatology ,Anakinra ,Proteinuria ,biology ,medicine.diagnostic_test ,business.industry ,C-reactive protein ,General Medicine ,Tumor necrosis factor receptor associated periodic syndrome ,personalized medicine ,Canakinumab ,030104 developmental biology ,chemistry ,Erythrocyte sedimentation rate ,biology.protein ,Autoinflammation ,Corticosteroid ,Medicine ,medicine.symptom ,business ,medicine.drug - Abstract
Objective: To describe the role of biotechnological therapies in patients with tumor necrosis factor receptor associated periodic syndrome (TRAPS) and to identify any predictor of complete response.Methods: Clinical, laboratory, and therapeutic data from 44 Caucasian TRAPS patients treated with biologic agents were retrospectively collected in 16 Italian tertiary Centers.Results: A total of 55 biological courses with anakinra (n = 26), canakinumab (n = 16), anti-TNF-α agents (n = 10), and tocilizumab (n = 3) were analyzed. A complete response was observed in 41 (74.5%) cases, a partial response in 9 (16.4%) cases and a treatment failure in 5 (9.1%) cases. The frequency of TRAPS exacerbations was 458.2 flare/100 patients-year during the 12 months prior to the start of biologic treatment and 65.7 flare/100 patients-years during the first 12 months of therapy (p < 0.0001). The median duration of attacks was 5.00 (IQR = 10.50) days at the start of biologics and 1.00 (IQR = 0.00) days at the 12-month assessment (p < 0.0001). Likewise, a significant reduction was observed in the Autoinflammatory Disease Activity Index during the study period (p < 0.0001). A significant corticosteroid sparing effect was observed as early as the first 12 months of treatment both in the number of patients requiring corticosteroids (p = 0.025) and in the dosages employed (p < 0.0001). A significant reduction was identified in the erythrocyte sedimentation rate (p < 0.0001), C reactive protein (p < 0.0001), serum amyloid A (p < 0.0001), and in the 24-h proteinuria dosage during follow-up (p = 0.001). A relapsing-remitting disease course (OR = 0.027, C.I. 0.001–0.841, p = 0.040) and the frequency of relapses at the start of biologics (OR = 0.363, C.I. 0.301–0.953, p = 0.034) were significantly associated with a complete response. No serious adverse events were observed.Conclusions: Treatment with biologic agents is highly effective in controlling clinical and laboratory TRAPS manifestations. Patients with a relapsing-remitting course and a lower frequency of flares at the start of treatment show more likely a complete response to biologic agents.
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- 2021
383. Clinical Features at Onset and Genetic Characterization of Pediatric and Adult Patients with TNF-α Receptor—Associated Periodic Syndrome (TRAPS): A Series of 80 Cases from the AIDA Network
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Masen Abdel Jaber, Donato Rigante, Francesco La Torre, Ombretta Viapiana, Carlo Salvarani, Elena Verrecchia, Maria Cristina Maggio, Ludovico Luca Sicignano, Carla Gaggiano, Alessandra Renieri, Antonio Vitale, Piero Ruscitti, Salvatore Grosso, Jurgen Sota, Virginia Berlengiero, Roberto Giacomelli, Florenzo Iannone, Raffaele Manna, Lorenzo Dagna, Rolando Cimaz, Antonella Insalaco, Luca Cantarini, Giampaolo Merlini, Davide Montin, Viviana Gelardi, Maria Antonietta Mencarelli, José Hernández-Rodríguez, Giacomo Emmi, Alessandra Soriano, Francesco Caso, Bruno Frediani, Marco Cattalini, Luisa Ciarcia, Giuseppe Lopalco, Paola Parronchi, Laura Obici, Matteo Piga, Gaggiano C., Vitale A., Obici L., Merlini G., Soriano A., Viapiana O., Cattalini M., Maggio M.C., Lopalco G., Montin D., Jaber M.A., Dagna L., Manna R., Insalaco A., Piga M., La Torre F., Berlengiero V., Gelardi V., Ciarcia L., Emmi G., Ruscitti P., Caso F., Cimaz R., Hernandez-Rodriguez J., Parronchi P., Sicignano L.L., Verrecchia E., Iannone F., Sota J., Grosso S., Salvarani C., Frediani B., Giacomelli R., Mencarelli M.A., Renieri A., Rigante D., and Cantarini L.
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0301 basic medicine ,myalgia ,Male ,Abdominal pain ,Settore MED/16 - REUMATOLOGIA ,TNFRSF1A ,Gene mutation ,Gastroenterology ,0302 clinical medicine ,Pathology ,Medicine ,RB1-214 ,Pericarditis ,Child ,Prognosis ,Penetrance ,Inflamació ,Familial Mediterranean Fever ,AIDA network ,Estudi de casos ,Receptors, Tumor Necrosis Factor, Type I ,Child, Preschool ,Autoinflammation ,Female ,medicine.symptom ,Research Article ,Adult ,medicine.medical_specialty ,Article Subject ,Adolescent ,Genotype ,tumor necrosis factor ,Immunology ,Context (language use) ,Asymptomatic ,03 medical and health sciences ,Young Adult ,Internal medicine ,Animals ,Humans ,Retrospective Studies ,030203 arthritis & rheumatology ,Inflammation ,business.industry ,tumor necrosis factor, TRAPS, AIDA network ,Tumor Necrosis Factor-alpha ,Infant ,TRAPS ,Cell Biology ,Myalgia ,Biological product ,medicine.disease ,030104 developmental biology ,Mutation ,Case studies ,business ,Kidney disease - Abstract
This study explores demographic, clinical, and therapeutic features of tumor necrosis factor receptor-associated periodic syndrome (TRAPS) in a cohort of 80 patients recruited from 19 Italian referral Centers. Patients’ data were collected retrospectively and then analyzed according to age groups (disease onset before or after 16 years) and genotype (high penetrance (HP) and low penetrance (LP) TNFRSF1A gene variants). Pediatric- and adult-onset were reported, respectively, in 44 and 36 patients; HP and LP variants were found, respectively, in 32 and 44 cases. A positive family history for recurrent fever was reported more frequently in the pediatric group than in the adult group (p<0.05). With reference to clinical features during attacks, pericarditis and myalgia were reported more frequently in the context of adult-onset disease than in the pediatric age (with p<0.01 and p<0.05, respectively), while abdominal pain was present in 84% of children and in 25% of adults (p<0.01). Abdominal pain was significantly associated also to the presence of HP mutations (p<0.01), while oral aphthosis was more frequently found in the LP variant group (p<0.05). Systemic amyloidosis occurred in 25% of subjects carrying HP variants. As concerns laboratory features, HP mutations were significantly associated to higher ESR values (p<0.01) and to the persistence of steadily elevated inflammatory markers during asymptomatic periods (p<0.05). The presence of mutations involving a cysteine residue, abdominal pain, and lymphadenopathy during flares significantly correlated with the risk of developing amyloidosis and renal impairment. Conversely, the administration of colchicine negatively correlated to the development of pathologic proteinuria (p<0.05). Both NSAIDs and colchicine were used as monotherapy more frequently in the LP group compared to the HP group (p<0.01). Biologic agents were prescribed to 49 (61%) patients; R92Q subjects were more frequently on NSAIDs monotherapy than other patients (p<0.01); nevertheless, they required biologic therapy in 53.1% of cases. At disease onset, the latest classification criteria for TRAPS were fulfilled by 64/80 (80%) patients (clinical plus genetic items) and 46/80 (57.5%) patients (clinical items only). No statistically significant differences were found in the sensitivity of the classification criteria according to age at onset and according to genotype (p<0.05). This study describes one of the widest cohorts of TRAPS patients in the literature, suggesting that the clinical expression of this syndrome is more influenced by the penetrance of the mutation rather than by the age at onset itself. Given the high phenotypic heterogeneity of the disease, a definite diagnosis should rely on both accurate working clinical assessment and complementary genotype.
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- 2020
384. Efficacy of a single intra-articular HYMOVIS ONE injection for managing symptomatic hip osteoarthritis: A 12-month follow-up retrospective analysis of the ANTIAGE register data
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Orazio De Lucia, Gianfranco Gigliucci, Bruno Frediani, Giovanni Iolascon, Sergio Crimaldi, Calogero Foti, Alberto Migliore, Migliore, A., Frediani, B., Gigliucci, G., Foti, C., Crimaldi, S., De Lucia, O., and Iolascon, G.
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lcsh:Diseases of the musculoskeletal system ,Visual analogue scale ,HYMOVIS ONE ,Osteoarthritis ,HYADD4-G ,hip osteoarthritis ,viscosupplementation ,Viscosupplementation ,Settore MED/34 ,lcsh:Orthopedic surgery ,Orthopedic Research and Reviews ,Hip osteoarthritis ,Medicine ,Orthopedics and Sports Medicine ,Adverse effect ,Original Research ,business.industry ,Ultrasound ,medicine.disease ,Hip osteoarthriti ,lcsh:RD701-811 ,Register data ,Anesthesia ,lcsh:RC925-935 ,business ,Body mass index ,Cohort study - Abstract
Alberto Migliore,1,2 Bruno Frediani,3 Gianfranco Gigliucci,1 Calogero Foti,4 Sergio Crimaldi,5 Orazio De Lucia,6 Giovanni Iolascon7 1Rheumatology Unit, S. Pietro FBF Hospital, Rome, Italy; 2Department of Internal Medicine, S. Pietro FBF Hospital, Rome, Italy; 3Medical and Surgical Science and Neuroscience Department, Rheumatology Section, University of Siena, O.U. of Osteo-Articular Diagnostic Procedures, Siena, Italy; 4Physical and Rehabilitation Medicine Department, University of Rome Tor Vergata, Rome, Italy; 5Orthopaedics and Traumatology Department, Lucca Hospital, USL Tuscany Northwest, Lucca, Italy; 6Division of Rheumatology, Gaetano Pini Institute, Milan, Italy; 7Physical and Rehabilitation Medicine Department, Napoli University, Naples, ItalyCorrespondence: Alberto MiglioreDepartment of Internal Medicine, S. Pietro FBF Hospital, Rome 00189, ItalyTel +39 049 7443620Fax +39 049 7443622Email alberto.migliore.12@outlook.itPurpose: The use of ultrasound (US) guidance has allowed hip osteoarthritis to be treated with intra-articular (IA) injections. HYMOVIS ONE (HYADD4-G) is a new hyaluronic acid (HA) derivative product with unusual characteristics, and it has been used with good results in knee osteoarthritis (OA). This study assessed the efficacy and safety of a single HYMOVIS ONE injection in patients affected by symptomatic hip OA.Patients and Methods: This post-marketing cohort study assessed data from the ANTIAGE Register. Inclusion criteria were age ≥ 40 years, symptomatic hip OA (Kellgren-Lawrence grade I–III) of ≥ 1-year duration, and ≥ 12 months follow-up. All patients received a single HYMOVIS ONE (32 mg/4 mL) injection at baseline. Values for 10-cm visual analogue scale (VAS) pain scores, the Lequesne index, and nonsteroidal anti–inflammatory drug (NSAID) consumption were evaluated at 6 and 12 months. Adverse events were also recorded.Results: The included patients (n = 198) consisted of 42.5% women, with a mean (± SD) age at baseline of 62 (± 14.2) years and a mean (± SD) body mass index of 26.3 (± 2.5). The mean (SD) Lequesne index and VAS pain scores at baseline were 11.5 (± 4.6) and 6.4 cm (± 2.2), respectively. All groups exhibited statistically significant reductions at all time points compared to baseline. At 12 months, the VAS pain score was reduced by 17.2%, the Lequesne index by 33.7%, and NSAID consumption by 41.7%.Conclusion: Our study supports the clinical efficacy and safety of a single HYMOVIS ONE injection for managing symptoms in patients with hip OA, confirming previous data on the use of HYMOVIS as a background therapy in the management of knee osteoarthritis.Keywords: hip osteoarthritis, viscosupplementation, HYMOVIS ONE, HYADD4-G
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- 2020
385. Comparison of early vs. delayed anakinra treatment in patients with adult onset still's disease and effect on clinical and laboratory outcomes
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Antonio Vitale, Giulio Cavalli, Piero Ruscitti, Jurgen Sota, Serena Colafrancesco, Roberta Priori, Guido Valesini, Lorenza Maria Argolini, Elena Baldissera, Elena Bartoloni, Daniele Cammelli, Giovanni Canestrari, Elena Cavallaro, Maria Grazia Massaro, Paola Cipriani, Ginevra De Marchi, Salvatore De Vita, Giacomo Emmi, Micol Frassi, Roberto Gerli, Elisa Gremese, Florenzo Iannone, Marco Fornaro, Anna Paladini, Giuseppe Lopalco, Raffaele Manna, Alessandro Mathieu, Carlomaurizio Montecucco, Marta Mosca, Ilaria Piazza, Matteo Piga, Irene Pontikaki, Micol Romano, Silvia Rossi, Maurizio Rossini, Elena Silvestri, Chiara Stagnaro, Rosaria Talarico, Bruno Frediani, Angela Tincani, Ombretta Viapiana, Gianfranco Vitiello, Paola Galozzi, Paolo Sfriso, Carla Gaggiano, Salvatore Grosso, Donato Rigante, Lorenzo Dagna, Roberto Giacomelli, Luca Cantarini, Vitale, A., Cavalli, G., Ruscitti, P., Sota, J., Colafrancesco, S., Priori, R., Valesini, G., Argolini, L. M., Baldissera, E., Bartoloni, E., Cammelli, D., Canestrari, G., Cavallaro, E., Massaro, M. G., Cipriani, P., De Marchi, G., De Vita, S., Emmi, G., Frassi, M., Gerli, R., Gremese, E., Iannone, F., Fornaro, M., Paladini, A., Lopalco, G., Manna, R., Mathieu, A., Montecucco, C., Mosca, M., Piazza, I., Piga, M., Pontikaki, I., Romano, M., Rossi, S., Rossini, M., Silvestri, E., Stagnaro, C., Talarico, R., Frediani, B., Tincani, A., Viapiana, O., Vitiello, G., Galozzi, P., Sfriso, P., Gaggiano, C., Grosso, S., Rigante, D., Dagna, L., Giacomelli, R., and Cantarini, L.
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0301 basic medicine ,myalgia ,medicine.medical_specialty ,Settore MED/16 - REUMATOLOGIA ,adult onset Still's disease ,anakinra ,autoinflammatory diseases ,innovative biotechnologies ,interleukin-1 ,personalized medicine ,systemic onset juvenile idiopathic arthritis ,treat to target ,Etanercept ,03 medical and health sciences ,0302 clinical medicine ,systemic onset juvenile idiopathic arthriti ,autoinflammatory disease ,Internal medicine ,Still's disease ,medicine ,Original Research ,030203 arthritis & rheumatology ,Anakinra ,lcsh:R5-920 ,innovative biotechnologie ,medicine.diagnostic_test ,biology ,business.industry ,C-reactive protein ,Hydroxychloroquine ,General Medicine ,medicine.disease ,Systemic-onset juvenile idiopathic arthritis ,Infliximab ,030104 developmental biology ,Erythrocyte sedimentation rate ,biology.protein ,Medicine ,medicine.symptom ,business ,lcsh:Medicine (General) ,medicine.drug - Abstract
Background: Aim of this study was to search for any difference in the outcome of patients with adult onset Still's disease (AOSD) treated with anakinra (ANK) in relation with the interval between disease onset and the start of anti-interleukin(IL)-1 treatment and according with the different lines of ANK treatment. Patients and Methods: One hundred and forty-one AOSD patients treated with ANK have been retrospectively assessed. Statistically significant differences (p < 0.05) were analyzed in the frequency of ANK effectiveness, primary or secondary inefficacy to ANK and rate of resolution of clinical and laboratory AOSD manifestations after 3, 6, and 12 months since ANK treatment according with different lines of treatment and different times between AOSD onset and start of ANK. Results: No significant differences were identified in the ANK effectiveness and frequency of primary or secondary inefficacy for patients starting ANK within 6 months (p = 0.19, p = 0.14, and p = 0.81, respectively) or 12 months (p = 0.37, p = 0.23, and p = 0.81, respectively) since AOSD onset compared with patients starting ANK thereafter; no significant differences were identified in ANK effectiveness and primary or secondary inefficacy according with different lines of ANK treatment (p = 0.06, p = 0.19, and p = 0.13, respectively). Patients starting ANK within 6 and 12 months since AOSD onset showed a significantly quicker decrease of erythrocyte sedimentation rate and C-reactive protein than observed among patients undergoing ANK treatment after 6 and 12 months. The number of swollen joints at the 3 month follow-up visit was significantly lower among patients undergoing ANK within 6 months since AOSD onset (p = 0.01), while no significance was identified at the 6 and 12 month assessments (p = 0.23 and p = 0.45, respectively). At the 3 and 6 month visits, the number of swollen joints was significantly higher among patients previously treated with conventional and biological disease modifying anti-rheumatic drugs (DMARDs) compared with those formerly treated only with conventional DMARDs (p < 0.017). Conclusions: Clinical and therapeutic outcomes are substantially independent of how early ANK treatment is started in AOSD patients. However, a faster ANK effectiveness in controlling systemic inflammation and resolving articular manifestations may be observed in patients benefiting from IL-1 inhibition as soon as after disease onset.
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- 2020
386. Assessing Risk of Osteoporotic Fractures in Primary Care: Development and Validation of the FRA-HS Algorithm
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Alessandro Pasqua, Iacopo Cricelli, Maria Luisa Brandi, Claudio Cricelli, Bruno Frediani, Elisa Bianchini, Daniel Prieto-Alhambra, Raffaella Michieli, Francesco Lapi, Giampiero Mazzaglia, Lapi, F, Bianchini, E, Michieli, R, Pasqua, A, Cricelli, I, Mazzaglia, G, Frediani, B, Prieto-Alhambra, D, Brandi, M, and Cricelli, C
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Adult ,Male ,medicine.medical_specialty ,Bone density ,Endocrinology, Diabetes and Metabolism ,Population ,Osteoporosis ,030209 endocrinology & metabolism ,Osteoporotic fracture ,Risk Assessment ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Bone Density ,Risk Factors ,Internal medicine ,FRA-HS Score ,Humans ,Medicine ,Orthopedics and Sports Medicine ,Femur ,030212 general & internal medicine ,education ,Aged ,education.field_of_study ,Primary Health Care ,Hip Fractures ,business.industry ,Middle Aged ,Primary care ,Explained variation ,medicine.disease ,Italy ,Calibration ,Orthopedic surgery ,Physical therapy ,Female ,business ,Risk assessment ,Algorithms ,Osteoporotic Fractures ,Cohort study - Abstract
We aimed to develop and validate the FRActure Health Search (FRA-HS) score for prediction of risk of osteoporotic fractures in primary care in Italy. We selected a cohort of patients aged 40 years between 1999 and 2002. They were followed until the occurrence of osteoporotic fracture, death, end of data registration, or end of data availability (December 31, 2012). Age, sex, history of osteoporotic fractures, secondary osteoporosis, long-term use of corticosteroids, rheumatoid arthritis, body mass index, smoking, and alcohol abuse/alcohol-related diseases, and the interaction terms sex*use of corticosteroids and age*secondary osteoporosis were entered in a competing-risk regression (Fine and Gray method) to predict the risk of hip/femur or overall major osteoporotic fractures. The coefficients were combined to obtain the FRA-HS for individual patients. Explained variance, discrimination, and calibration measures were computed to evaluate the models accuracy. The final model was tested using an independent data source. The FRA-HS explained 47.36 and 20.6% of the variation for occurrence of hip/femur and overall major osteoporotic fractures, respectively. Area Under Curve was 0.77 and 0.73, respectively. Predicted/observed ratios revealed a margin of error lower than 30% in the 80% of the population. After stratifying by sex, prediction models for hip/femur fractures confirmed acceptable accuracy in both sexes, while poor explained variance (
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- 2017
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387. Ultrasound in the diagnosis of calcium pyrophosphate dihydrate deposition disease. A systematic literature review and a meta-analysis
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Ca Scirè, Georgios Filippou, I. Bertoldi, V. Di Sabatino, Marco A. Cimmino, V. Picerno, Annamaria Iagnocco, Antonella Adinolfi, Emilio Filippucci, Bruno Frediani, Luca Maria Sconfienza, A. Delle Sedie, Filippou, G, Adinolfi, A, Iagnocco, A, Filippucci, E, Cimmino, M, Bertoldi, I, Di Sabatino, V, Picerno, V, Delle Sedie, A, Sconfienza, L, Frediani, B, and Scire, C
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medicine.medical_specialty ,Crystal arthropathies ,Biomedical Engineering ,Chondrocalcinosis ,Disease ,Calcium Pyrophosphate ,NO ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Rheumatology ,medicine ,Crystal arthropathy ,Humans ,Orthopedics and Sports Medicine ,Medical physics ,030212 general & internal medicine ,Calcium Pyrophosphate Dihydrate Deposition ,Ultrasonography ,030203 arthritis & rheumatology ,business.industry ,Synovial fluid analysi ,Ultrasound ,Calcium pyrophosphate ,Radiology ,Synovial fluid analysis ,Systematic review ,medicine.disease ,Surgery ,Chondrocalcinosi ,chemistry ,Meta-analysis ,business ,Crystal arthropathie - Abstract
Summary Objective Ultrasonography (US) demonstrated to be a promising tool for the diagnosis of calcium pyrophosphate dihydrate deposition disease (CPPD). The aim of this systematic literature review (SLR) was to collect the definitions for the US elementary lesions and to summarize the available data about US diagnostic accuracy in CPPD. Methods We systematically reviewed all the studies that considered US as the index test for CPPD diagnosis without restrictions about the reference test or that provided definitions about US identification of CPPD. Sensitivity and specificity were calculated for each study and definitions were extrapolated. Subgroup analyses were planned by anatomical site included in the index text and different reference standards. Results Thirty-seven studies were included in this review. All the studies were eligible for the collection of US findings and all definitions were summarized. US description of elementary lesions appeared heterogeneous among the studies. Regarding US accuracy, 13 articles entered in the meta-analysis. Considering each joint structure, the sensitivity ranged between 0.77 (0.63–0.87) and 0.34 (0.16–0.58) while the specificity varies between 1.00 (0.89–1.00) and 0.92 (0.16–1.00). Considering the reference standards used, the sensibility ranged between 0.34 (0.02–0.65) and 0.87 (0.76–0.99) while specificity ranged between 0.84 (0.52–1.00) and 1.00 (0.99–1.00). Conclusion US is potentially a useful tool for the diagnosis of CPPD but universally accepted definitions and further testing are necessary in order to assess the role of the technique in the diagnostic process.
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- 2016
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388. Total body x-ray absorptiometry: Performance and clinical applications
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Nuti, R., Martini, G., Righi, G., Turchetti, V., and Frediani, B.
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- 1990
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389. Prognostic bioindicators in severe COVID-19 patients.
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Bergantini, L., Bargagli, E., d'Alessandro, M., Refini, R.M., Cameli, P., Galasso, L., Scapellato, C., Montagnani, F., Scolletta, S., Franchi, F., Valente, S., Bennett, D., Sebastiani, G., Frediani, B., and Dotta, F.
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COVID-19 , *BIOINDICATORS , *SARS-CoV-2 , *RECEIVER operating characteristic curves , *INTRAVENOUS therapy , *INFLAMMATORY mediators , *ENZYME-linked immunosorbent assay - Abstract
Severe acute respiratory syndrome caused by novel coronavirus 2 (SARS-CoV-2) emerged in Wuhan (China) in December 2019. Here we evaluated a panel of biomarkers to phenotype patients and to define the role of immuno-inflammatory mediators as biomarkers of severity. Serum samples were obtained from 24 COVID-19 patients on admission to hospital, before any treatment or infusion of intravenous steroids or invasive ventilation. KL-6 IL-6 and C-peptide were measured by chemiluminescent enzyme immunoassay. IL-6 assay was validated for accuracy and precision. The validity of variables used to distinguish severe from mild-to-moderate patients was assessed by areas under curves (AUC) of the receiver operating characteristic (ROC) and logistic regression was performed to combine parameters of the two groups. In the severe group, IL-6, CRP and KL-6 concentrations were significantly higher than in mild-to-moderate patients. KL-6, IL-6 and CRP concentrations were directly correlated with each other. ROC curve analysis of the logistic regression model including IL-6, KL-6 and CRP showed the best performance with an AUC of 0.95. Besides corroborating previous reports of over-expression of IL-6 in severe COVID-19 patients requiring mechanical ventilation, analytical determination of other mediators showed that IL-6 concentrations were correlated with those of KL-6 and CRP. The combination of these three prognostic bioindicators made it possible to distinguish severe COVID-19 patients with poor prognosis from mild-to-moderate patients. [ABSTRACT FROM AUTHOR]
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- 2021
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390. A comprehensive comparison between pediatric and adult patients with periodic fever, aphthous stomatitis, pharyngitis, and cervical adenopathy (PFAPA) syndrome
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Marco Francesco Natale, Florenzo Iannone, Bruno Frediani, Francesca D’Errico, Luca Cantarini, Antonio Vitale, Donato Rigante, Giuseppe Lopalco, Laura Andreozzi, Rigante D., Vitale A., Natale M.F., Lopalco G., Andreozzi L., Frediani B., D'Errico F., Iannone F., and Cantarini L.
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myalgia ,Male ,Pediatrics ,medicine.medical_treatment ,Recurrent pharyngitis ,Adrenal Cortex Hormone ,Adulthood ,Autoinflammatory disorders ,Childhood ,PFAPA syndrome ,Prednisone ,Tonsillectomy ,0302 clinical medicine ,Adrenal Cortex Hormones ,Recurrence ,Medicine ,Age Factor ,030212 general & internal medicine ,Child ,Stomatitis ,Age Factors ,Pharyngitis ,General Medicine ,Syndrome ,Middle Aged ,Phenotype ,Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA ,Stomatitis, Aphthous ,Female ,medicine.symptom ,Stomatitis, Aphthou ,medicine.drug ,Human ,Lymphadeniti ,Adult ,medicine.medical_specialty ,Fever ,03 medical and health sciences ,Rheumatology ,Lymphadenitis ,Humans ,Lymphatic Diseases ,030203 arthritis & rheumatology ,Inflammation ,business.industry ,Adenitis ,medicine.disease ,Surgery ,Autoinflammatory disorder ,Pharyngiti ,Lymphatic Disease ,business - Abstract
Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenopathy (PFAPA) syndrome is a mysterious disorder characterized by periodically recurrent fevers, oropharyngeal inflammation, and adenitis, which mainly affects children, though in very recent times, it has been also recognized in adulthood. We enrolled 115 unrelated pediatric and adult patients with history of periodic fevers who fulfilled the current diagnostic criteria for PFAPA syndrome in three Italian referral centers and highlighted differences between children and adults. Eighty-five children and 30 adults were evaluated: the frequency of flares was significantly higher in pediatric cases, while febrile attack duration was significantly longer in adults. Clockwork periodicity of fever and recurrent pharyngitis were more frequently observed in childhood, but no differences were identified for aphthosis and cervical adenopathy. Conversely, joint symptoms, myalgia, headache, fatigue, ocular signs, and rashes were more common in adults. The simultaneous occurrence of two or three cardinal PFAPA signs did not show any statistical difference between the groups, while the occurrence of only one cardinal manifestation was more frequent in adults. Corticosteroids were effective in 98.82% of children and 88.2% of adults. Tonsillectomy was rarely performed, resulting effective in only two patients. Our data illustrate the clinical overlap between pediatric and adult cases of PFAPA syndrome. Adults are characterized by a wider repertoire of inflammatory signs, suggesting that onset in adulthood might leave the disease misdiagnosed. Clinicians, not only pediatricians, should take into account this clinical entity in every patient of whatever age suffering from recurrent fevers of unknown origin.
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- 2017
391. The epidemiology of osteoporosis in Italian postmenopausal women according to the National Bone Health Alliance (NBHA) diagnostic criteria: a multicenter cohort study
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Luciano Nieddu, Andrea Giustina, Davide Gatti, Addolorata Corrado, Francesco Paolo Cantatore, Maurizio Rossini, Cristiana Cipriani, Salvatore Minisola, M. Di Stefano, G. Bianchi, Bruno Frediani, T Porcelli, G.C. Isaia, G. Girasole, Mario Pedrazzoni, Jessica Pepe, Francesco Bertoldo, Cipriani, C., Pepe, J., Bertoldo, F., Bianchi, G., Cantatore, F. P., Corrado, A., Di Stefano, M., Frediani, B., Gatti, D., Giustina, Andrea, Porcelli, T., Isaia, G., Rossini, M., Nieddu, L., Minisola, S., Girasole, G., and Pedrazzoni, M.
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musculoskeletal diseases ,0301 basic medicine ,medicine.medical_specialty ,FRAX ,Endocrinology, Diabetes and Metabolism ,Osteoporosis ,030209 endocrinology & metabolism ,FRAX® ,Risk Assessment ,Cohort Studies ,DeFRA ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Bone Density ,FRAX® ,Epidemiology ,Prevalence ,medicine ,Humans ,risk factors ,deFRA ,fracture ,Italy ,osteoporosis ,endocrinology, diabetes and metabolism ,endocrinology ,Fracture ,Risk factors ,Osteoporosis, Postmenopausal ,diabetes and metabolism ,Aged ,Femoral neck ,Hip fracture ,Femur fracture ,business.industry ,Osteoporosi ,Middle Aged ,Anthropometry ,medicine.disease ,Postmenopause ,Cross-Sectional Studies ,030104 developmental biology ,medicine.anatomical_structure ,Physical therapy ,Female ,Risk factor ,business ,Osteoporotic Fractures ,Cohort study - Abstract
Purpose: The study was aimed at evaluating the prevalence of osteoporosis, defined by BMD and the National Bone Health Alliance (NBHA) criteria, and the prevalence of clinical risk factors for fractures in Italian postmenopausal women. Methods: This is a cross-sectional, multicenter, cohort study evaluating 3247 postmenopausal women aged ⥠50 and older in different areas of Italy in the period 2012â2014. All the participants were evaluated as far as anthropometrics; questionnaires for FRAX® and DeFRA calculation were administered and bone mineral density was measured at lumbar spine, femoral neck and total hip by DXA. Results: The prevalence of osteoporosis, as assessed by BMD and NBHA criteria was 36.6 and 57%, respectively. Mean ± SD values of FRAX® and DeFRA were: 10.2 ± 7.3 and 11 ± 9.4 for major fractures, and 3.3 ± 4.9 and 3.9 ± 5.9 for hip fractures, respectively. Among clinical risk factors for fracture, the presence of previous fracture, particularly non-spine/non-hip fracture, parental history of hip fracture and current smoking were the most commonly observed. Conclusions: Our study showed that more that the half of postmenopausal women aged 50 and older in Italy has osteoporosis on the basis of the NBHA criteria. There is a relevant high risk of femur fracture, as assessed by the FRAX® and DeFRA and previous fracture, parental history of hip fracture and current smoking are the most common risk factors. The data should be considered particularly in relation to the need to increase prevention strategies on modifiable risk factors and therapeutic intervention.
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- 2017
392. Prevalence and incidence of osteoporotic fractures in patients on long-term glucocorticoid treatment for rheumatic diseases: The glucocorticoid induced OsTeoporosis TOol (GIOTTO) study
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O. Di Munno, P. Delvino, Ombretta Viapiana, Walter Grassi, Nazzarena Malavolta, Maurizio Rossini, R. Nuti, Bruno Frediani, Clodoveo Ferri, Gianantonio Saviola, Maurizio Muratore, Francesco Paolo Cantatore, L. Mirone, A. Mathieu, Gianfranco Ferraccioli, Laura Bogliolo, Ilaria Piazza, Maria Vitiello, G. La Montagna, C. U. Manzini, S. Maddali Bongi, A. Del Puente, Davide Gatti, Gaia Tripi, Rossini, M., Viapiana, O., Vitiello, M., Malavolta, N., La Montagna, G., Maddali Bongi, S., Di Munno, O., Nuti, R., Manzini, C. U., Ferri, C., Bogliolo, L., ST-LAURENT, Mathieu, Cantatore, F., Del Puente, A., Muratore, M., Grassi, W., Frediani, B., Saviola, G., Delvino, P., Mirone, L., Ferraccioli, G., Tripi, G., Piazza, I., and Gatti, D.
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Male ,Settore MED/16 - REUMATOLOGIA ,Cross-sectional study ,Osteoporosis ,lcsh:Medicine ,Arthritis, Rheumatoid ,0302 clinical medicine ,Rheumatic diseases ,Glucocorticoid ,Prednisone ,Risk Factors ,Prevalence ,030212 general & internal medicine ,Longitudinal Studies ,Vitamin D ,Aged, 80 and over ,Fractures ,Glucocorticoids ,Rheumatology ,Bone Density Conservation Agents ,Diphosphonates ,Incidence (epidemiology) ,Incidence ,Middle Aged ,osteoporosis, glucocorticoids, placebo ,medicine.anatomical_structure ,Treatment Outcome ,Italy ,Rheumatoid arthritis ,Female ,medicine.drug ,Adult ,medicine.medical_specialty ,lcsh:Internal medicine ,Polymyalgia rheumatica ,03 medical and health sciences ,Internal medicine ,Rheumatic Diseases ,medicine ,Humans ,lcsh:RC31-1245 ,Femoral neck ,Aged ,030203 arthritis & rheumatology ,business.industry ,lcsh:R ,Osteoporosi ,medicine.disease ,fractures ,Surgery ,Cross-Sectional Studies ,Fracture ,Polymyalgia Rheumatica ,placebo ,Rheumatic disease ,business ,Osteoporotic Fractures - Abstract
Osteoporosis and fractures are common and invalidating consequences of chronic glucorticoid (GC) treatment. Reliable information regarding the epidemiology of GC induced osteoporosis (GIOP) comes exclusively from the placebo group of randomized clinical trials while observational studies are generally lacking data on the real prevalence of vertebral fractures, GC dosage and primary diagnosis. The objective of this study was to evaluate the prevalence and incidence of osteoporotic fractures and to identify their major determinants (primary disease, GC dosage, bone mineral density, risk factors, specific treatment for GIOP) in a large cohort of consecutive patients aged >21 years, on chronic treatment with GC (≥5 mg prednisone - PN - equivalent) and attending rheumatology centers located all over Italy. Glucocorticoid Induced OsTeoporosis TOol (GIOTTO) is a national multicenter cross-sectional and longitudinal observational study. 553 patients suffering from Rheumatoid Arthritis (RA), Polymyalgia Rheumatica (PMR) and Connective Tissue Diseases (CTDs) and in chronic treatment with GCs were enrolled. Osteoporotic BMD values (T score
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- 2017
393. Anti-interleukin-1 treatment in patients with rheumatoid arthritis and type 2 diabetes (TRACK): A multicentre, open-label, randomised controlled trial
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Immacolata Prevete, Paolo Airò, Francesco Paolo Cantatore, Virginia D'Abrosca, Saverio Alvaro, Bruno Frediani, Luigi Sinigaglia, Daniela Iacono, Norma Battafarano, Ombretta Viapiana, Ilenia Pantano, Micol Frassi, Francesco Masedu, Vasiliki Liakouli, Marco Valenti, Luca Cantarini, Piero Ruscitti, Roberta Maggio, Paola Cipriani, Rita Mulè, Roberto Giacomelli, Giorgio Carlino, Ruscitti, P., Masedu, F., Alvaro, S., Airo, P., Battafarano, N., Cantarini, L., Cantatore, F. P., Carlino, G., D'Abrosca, V., Frassi, M., Frediani, B., Iacono, D., Liakouli, V., Maggio, R., Mule, R., Pantano, I., Prevete, I., Sinigaglia, L., Valenti, M., Viapiana, O., Cipriani, P., and Giacomelli, R.
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Blood Glucose ,Male ,Glycated Hemoglobin A ,Time Factors ,Physiology ,030204 cardiovascular system & hematology ,Pathology and Laboratory Medicine ,Biochemistry ,Etanercept ,Arthritis, Rheumatoid ,Endocrinology ,0302 clinical medicine ,Drug Metabolism ,Rheumatoid ,Immune Physiology ,Receptors ,Medicine and Health Sciences ,Diabetes diagnosis and management ,Insulin ,Medicine ,030212 general & internal medicine ,Certolizumab pegol ,Immune Response ,Innate Immune System ,Pharmaceutics ,General Medicine ,Middle Aged ,Type 2 Diabetes ,Treatment Outcome ,Italy ,Antirheumatic Agents ,Rheumatoid arthritis ,Number needed to treat ,Cytokines ,Female ,Type 2 ,Research Article ,medicine.drug ,medicine.medical_specialty ,HbA1c ,Endocrine Disorders ,Immunology ,Rheumatoid Arthritis ,Autoimmune Diseases ,03 medical and health sciences ,Signs and Symptoms ,Rheumatology ,Drug Therapy ,Internal medicine ,Diabetes Mellitus ,Adalimumab ,Humans ,Pharmacokinetics ,Hemoglobin ,Aged ,Inflammation ,Diabetic Endocrinology ,Pharmacology ,Glycated Hemoglobin ,Anakinra ,business.industry ,Arthritis ,Biology and Life Sciences ,Proteins ,Receptors, Interleukin-1 ,Molecular Development ,medicine.disease ,Diagnostic medicine ,Hormones ,Infliximab ,Golimumab ,Interleukin 1 Receptor Antagonist Protein ,Diabetes Mellitus, Type 2 ,Metabolic Disorders ,Immune System ,Clinical Immunology ,Tumor Necrosis Factor Inhibitors ,Clinical Medicine ,business ,Biomarkers ,Interleukin-1 ,Developmental Biology - Abstract
Background The inflammatory contribution to type 2 diabetes (T2D) has suggested new therapeutic targets using biologic drugs designed for rheumatoid arthritis (RA). On this basis, we aimed at investigating whether interleukin-1 (IL-1) inhibition with anakinra, a recombinant human IL-1 receptor antagonist, could improve both glycaemic and inflammatory parameters in participants with RA and T2D compared with tumour necrosis factor (TNF) inhibitors (TNFis). Methods and findings This study, designed as a multicentre, open-label, randomised controlled trial, enrolled participants, followed up for 6 months, with RA and T2D in 12 Italian rheumatologic units between 2013 and 2016. Participants were randomised to anakinra or to a TNFi (i.e., adalimumab, certolizumab pegol, etanercept, infliximab, or golimumab), and the primary end point was the change in percentage of glycated haemoglobin (HbA1c%) (EudraCT: 2012-005370-62 ClinicalTrial.gov: NCT02236481). In total, 41 participants with RA and T2D were randomised, and 39 eligible participants were treated (age 62.72 ± 9.97 years, 74.4% female sex). The majority of participants had seropositive RA disease (rheumatoid factor and/or anticyclic citrullinated peptide antibody [ACPA] 70.2%) with active disease (Disease Activity Score-28 [DAS28]: 5.54 ± 1.03; C-reactive protein 11.84 ± 9.67 mg/L, respectively). All participants had T2D (HbA1c%: 7.77 ± 0.70, fasting plasma glucose: 139.13 ± 42.17 mg). When all the enrolled participants reached 6 months of follow-up, the important crude difference in the main end point, confirmed by an unplanned ad interim analysis showing the significant effects of anakinra, which were not observed in the other group, led to the study being stopped for early benefit. Participants in the anakinra group had a significant reduction of HbA1c%, in an unadjusted linear mixed model, after 3 months (β: −0.85, p < 0.001, 95% CI −1.28 to −0.42) and 6 months (β: −1.05, p < 0.001, 95% CI −1.50 to −0.59). Similar results were observed adjusting the model for relevant RA and T2D clinical confounders (male sex, age, ACPA positivity, use of corticosteroids, RA duration, T2D duration, use of oral antidiabetic drug, body mass index [BMI]) after 3 months (β: −1.04, p < 0.001, 95% CI −1.52 to −0.55) and 6 months (β: −1.24, p < 0.001, 95% CI −1.75 to −0.72). Participants in the TNFi group had a nonsignificant slight decrease of HbA1c%. Assuming the success threshold to be HbA1c% ≤ 7, we considered an absolute risk reduction (ARR) = 0.42 (experimental event rate = 0.54, control event rate = 0.12); thus, we estimated, rounding up, a number needed to treat (NNT) = 3. Concerning RA, a progressive reduction of disease activity was observed in both groups. No severe adverse events, hypoglycaemic episodes, or deaths were observed. Urticarial lesions at the injection site led to discontinuation in 4 (18%) anakinra-treated participants. Additionally, we observed nonsevere infections, including influenza, nasopharyngitis, upper respiratory tract infection, urinary tract infection, and diarrhoea in both groups. Our study has some limitations, including open-label design and previously unplanned ad interim analysis, small size, lack of some laboratory evaluations, and ongoing use of other drugs. Conclusions In this study, we observed an apparent benefit of IL-1 inhibition in participants with RA and T2D, reaching the therapeutic targets of both diseases. Our results suggest the concept that IL-1 inhibition may be considered a targeted treatment for RA and T2D. Trial registration The trial is registered with EU Clinical Trials Register, EudraCT Number: 2012-005370-62 and with ClinicalTrial.gov, number NCT02236481., Roberto Giacomelli and co-authors study treatment of comorbid rheumatoid arthritis and type 2 diabetes via interleukin-1 blockade., Author summary Why was this study done? A growing body of evidence suggests the inflammatory contribution to type 2 diabetes (T2D) as observed in rheumatoid arthritis (RA). Interleukin-1 (IL-1) would be a common pathogenic mediator in T2D and RA, suggesting a possible common therapeutic target. We investigated whether IL-1 inhibition with anakinra, a human IL-1-receptor antagonist, could improve both glycaemic and inflammatory parameters in participants with RA and T2D compared with tumour necrosis factor (TNF) inhibitors (TNFis). What did the researchers do and find? In a multicentre, open-label, randomised controlled trial, 39 participants with RA and T2D (age 62.72 ± 9.97 years, 74.4% female sex) were randomised to anakinra or to TNFi in order to evaluate the efficacy of these drugs in controlling the metabolic alterations of T2D. Anakinra showed a significant improvement of metabolic alteration (reduction of percentage of glycated haemoglobin [HbA1c%]) after both 3 months and 6 months of therapy (crude difference of 0.93 HbA1c% between groups), whereas TNFi did not show any significant improvement on these features. No severe adverse events, hypoglycaemic episodes, or deaths were observed. What do these findings mean? Our results suggest the concept that IL-1 inhibition may be considered a targeted treatment for RA and T2D. Managing the inflammatory disease and the metabolic comorbidity by an agent inhibiting IL-1 may lead to a consequent beneficial impact on participants’ compliance, their overall cardiovascular (CV) risk, and the burden of healthcare costs. Our study has some limitations, mainly due to open-label design, and future studies are necessary to fully clarify this topic.
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- 2019
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394. The challenge of the definition of early symptomatic knee osteoarthritis: a proposal of criteria and red flags from an international initiative promoted by the Italian Society for Rheumatology
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Emmanuel Maheu, Carlo Alberto Scirè, Marco Matucci Cerinic, Xavier Chevalier, Nemanja Damjanov, Bruno Frediani, Luigi Di Matteo, Demirhan Diracoglu, Emanuele Bizzi, Rasho Rashkov, Durda Babic-Naglic, Spiros Aslanidis, Natalia Martusevich, Greta Carrara, Giovanni Minisola, Alberto Migliore, Gabriel Herrero-Beaumont, Gerolamo Bianchi, Jose Vicente Moreno Muelas, Gian Filippo Bagnato, Ruxandra Ionescu, Roberta Ramonda, Nurullah Akkoc, L. Denisov, L. Collaku, M. Scarpellini, Loreto Carmona, Tatiana Barskova, Jaime Branco, Migliore, A, Scire, C, Carmona, L, Beaumont, G, Bizzi, E, Branco, J, Carrara, G, Chevalier, X, Collaku, L, Aslanidis, S, Denisov, L, Di Matteo, L, Bianchi, G, Diracoglu, D, Frediani, B, Maheu, E, Martusevich, N, Bagnato, G, Scarpellini, M, Minisola, G, Akkoc, N, Ramonda, R, Barskova, T, Babic-Naglic, D, Muelas, J, Ionescu, R, Rashkov, R, Damjanov, N, and Cerinic, M
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Male ,Time Factors ,Delphi Technique ,Delphi method ,Osteoarthritis ,Knee Joint ,0302 clinical medicine ,Risk Factors ,Early diagnosis ,Knee joint ,Referral ,Female ,Focus Groups ,Humans ,Italy ,Osteoarthritis, Knee ,Qualitative Research ,Referral and Consultation ,Rheumatology ,Societies, Medical ,Symptom Assessment ,Consensus ,Early Diagnosis ,Immunology and Allergy ,Immunology ,Medicine ,030212 general & internal medicine ,Generalized pain ,Early diagnosi ,Systematic review ,Osteoarthriti ,medicine.symptom ,musculoskeletal diseases ,medicine.medical_specialty ,NO ,03 medical and health sciences ,Medical ,Internal medicine ,Knee ,030203 arthritis & rheumatology ,business.industry ,medicine.disease ,Knee pain ,Physical therapy ,Societies ,business - Abstract
The aim of this study was to establish consensus for potential early symptomatic knee osteoarthritis (ESKOA) clinical definition and referral criteria from primary care to rheumatologists, based on available data from literature and a qualitative approach, in order to perform studies on patients fulfilling such criteria and to validate the obtained ESKOA definition. A complex methodological approach was followed including: (1) three focus groups (FG), including expert clinicians, researchers and patients; (2) a systematic literature review (SLR); (3) two discussion groups followed by a Delphi survey. FG and SLR were performed in parallel to inform discussion groups in order to identify relevant constructs to be included in the modified Delphi survey. ESKOA is defined in the presence of: (a) two mandatory symptoms (knee pain in the absence of any recent trauma or injury and very short joint stiffness, lasting for less than 10min, when starting movement) even in the absence of risk factors, or (b) knee pain, and 1 or 2 risk factors or (c) three or more risk factors in the presence of at least one mandatory symptom, with symptoms lasting less than 6 months. These criteria are applicable in the absence of active inflammatory arthritis, generalized pain, Kellgren-Lawrence grade >0, any recent knee trauma or injury, and age lower than 40years. Knee pain in the absence of any recent trauma lasting for less than 6months was considered as the referral criterion to the rheumatologist for the suspicion of ESKOA. This consensus process has identified provisional clinical definition of ESKOA and defined potential referral criterion to rheumatologist, in order to test ESKOA obtained definition in prospective validation studies.
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- 2016
395. A Snapshot on the On-Label and Off-Label Use of the Interleukin-1 Inhibitors in Italy among Rheumatologists and Pediatric Rheumatologists: A Nationwide Multi-Center Retrospective Observational Study
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Fabrizio De Benedetti, Elena Cavallaro, Antonio Vitale, Elena Verrecchia, Alma Nunzia Olivieri, Maria Carla De Maggio, Leonardo Punzi, Giovanni Lapadula, Giuseppe Lopalco, Stefano Gentileschi, Lucia Cerrito, Florenzo Iannone, Marta Mosca, Paolo Sfriso, Giuseppe Paolazzi, Romina Gallizzi, Francesco La Torre, Gianfranco Vitiello, Serena Colafrancesco, Renzo Marcolongo, Chiara Stagnaro, Angela Tincani, Ginevra De Marchi, Carlo Salvarani, Raffaele Manna, Francesca Ricci, Ombretta Viapiana, Paola Galozzi, Mauro Galeazzi, Armin Maier, Rosaria Talarico, M Pardeo, Donato Rigante, Luca Cantarini, Salvatore De Vita, Rolando Cimaz, Maria Alessio, Antonella Insalaco, Claudia Fabiani, Giacomo Emmi, Alessandra Soriano, Micol Frassi, Marco Cattalini, Roberta Priori, Elena Silvestri, Bruno Frediani, Daniele Cammelli, Guido Valesini, Vitale, A., Insalaco, A., Sfriso, P., Lopalco, G., Emmi, G., Cattalini, M., Manna, R., Cimaz, R., Priori, R., Talarico, R., Gentileschi, S., de Marchi, G., Frassi, M., Gallizzi, R., Soriano, A., Alessio, M., Cammelli, D., Maggio, M. C., Marcolongo, R., La Torre, F., Fabiani, C., Colafrancesco, S., Ricci, F., Galozzi, P., Viapiana, O., Verrecchia, E., Pardeo, M., Cerrito, L., Cavallaro, E., Olivieri, A. N., Paolazzi, G., Vitiello, G., Maier, A., Silvestri, E., Stagnaro, C., Valesini, G., Mosca, M., de Vita, S., Tincani, A., Lapadula, G., Frediani, B., De Benedetti, F., Iannone, F., Punzi, L., Salvarani, C., Galeazzi, M., Rigante, D., Cantarini, L., Maggio, M., and Olivieri, A.
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medicine.medical_specialty ,autoinflammatory disorders, treatment, interleukin (IL)-1, anakinra, canakinumab ,Dose ,anakinra ,autoinflammatory disorders ,canakinumab ,interleukin (IL)-1 ,treatment ,030204 cardiovascular system & hematology ,Off-label use ,03 medical and health sciences ,Settore MED/38 - Pediatria Generale E Specialistica ,0302 clinical medicine ,Internal medicine ,medicine ,Pharmacology (medical) ,Interleukin-1 inhibitors ,Adverse effect ,Original Research ,030203 arthritis & rheumatology ,Pharmacology ,Anakinra ,business.industry ,lcsh:RM1-950 ,Autoinflammatory disorders ,Canakinumab ,Interleukin (IL)-1 ,Treatment ,Interleukin ,Retrospective cohort study ,Surgery ,lcsh:Therapeutics. Pharmacology ,Autoinflammatory disorder ,Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA ,Antirheumatic drugs ,business ,medicine.drug - Abstract
Background: Interleukin (IL)-1 inhibitors have been suggested as possible therapeutic options in a large number of old and new clinical entities characterized by an IL-1 driven pathogenesis. Objectives: To perform a nationwide snapshot of the on-label and off-label use of anakinra (ANA) and canakinumab (CAN) for different conditions both in children and adults. Methods: We retrospectively collected demographic, clinical, and therapeutic data from both adult and pediatric patients treated with IL-1 inhibitors from January 2008 to July 2016. Results: Five hundred and twenty-six treatment courses given to 475 patients (195 males, 280 females; 111 children and 364 adults) were evaluated. ANA was administered in 421 (80.04%) courses, CAN in 105 (19.96%). Sixty-two (32.1%) patients had been treated with both agents. IL-1 inhibitors were employed in 38 different indications (37 with ANA, 16 with CAN). Off-label use was more frequent for ANA than CAN (p < 0.0001). ANA was employed as first-line biologic approach in 323 (76.7%) cases, while CAN in 37 cases (35.2%). IL-1 inhibitors were associated with corticosteroids in 285 (54.18%) courses and disease modifying anti-rheumatic drugs (DMARDs) in 156 (29.65%). ANA dosage ranged from 30 to 200 mg/day (or 1.0-2.0 mg/kg/day) among adults and 2-4 mg/kg/day among children; regarding CAN, the most frequently used posologies were 150mg every 8 weeks, 150mg every 4 weeks and 150mg every 6 weeks. The frequency of failure was higher among patients treated with ANA at a dosage of 100 mg/day than those treated with 2 mg/kg/day (p = 0.03). Seventy-six patients (14.4%) reported an adverse event (AE) and 10 (1.9%) a severe AE. AEs occurred more frequently after the age of 65 compared to both children and patients aged between 16 and 65 (p = 0.003 and p = 0.03, respectively). Conclusions: IL-1 inhibitors are mostly used off-label, especially ANA, during adulthood. The high frequency of good clinical responses suggests that IL-1 inhibitors are used with awareness of pathogenetic mechanisms; adult healthcare physicians generally employ standard dosages, while pediatricians are more prone in using a weight-based posology. Dose adjustments and switching between different agents showed to be effective treatment strategies. Our data confirm the good safety profile of IL-1 inhibitors.
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- 2016
396. Assessing 5-year incidence rates and determinants of osteoporotic fractures in primary care
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Raffaella Michieli, Claudio Cricelli, Giampiero Mazzaglia, Francesco Lapi, Alessandro Pasqua, M. L. Brandi, Bruno Frediani, M Simonetti, Lapi, F, Simonetti, M, Michieli, R, Pasqua, A, Brandi, M, Frediani, B, Cricelli, C, and Mazzaglia, G
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Male ,Pediatrics ,medicine.medical_specialty ,Histology ,Databases, Factual ,Index date ,Epidemiology ,Physiology ,Endocrinology, Diabetes and Metabolism ,Risk-Factor ,MEDLINE ,Primary care ,Frax(R) ,Database ,Cohort Studies ,Hip Fracture ,Sex Factors ,White Women ,Risk Factors ,Prevalence ,Humans ,Medicine ,Osteoporotic fracture ,Longitudinal Studies ,Aged ,Aged, 80 and over ,Primary Health Care ,business.industry ,Incidence (epidemiology) ,Cohort ,Age Factors ,Men ,Middle Aged ,medicine.disease ,Costs ,Rheumatoid arthritis ,Physical therapy ,Female ,business ,Algorithms ,Osteoporotic Fractures ,Cohort study - Abstract
Purpose: To assess the gender and age-related 5-year incidence rates of osteoporotic fractures, and their related predictors, in a primary care setting. Methods: We obtained information from the Health Search-CSD Longitudinal Patients Database (HSD). This is an Italian General Practice data repository which comprises information given by computer-based patient records of a selected group of over 900 Primary Care Physicians (PCPs). We selected all patients aged 50 to 85 years, who were actively included into the PCP's list at the beginning of the enrolment period (1st January 2002-31st December 2003). We excluded individuals who were registered in the PCPs' list for less than 1 year before the entry date (Index date) into the cohort, as well as those who were diagnosed with Paget disease or malignant neoplasm. Participants were followed up until the occurrence of osteoporotic fracture, one of the exclusion criteria, or the end of the study period. Results: The 5-year rates (per 1000 person-years) of any osteoporotic fracture were 11.56 (95% C.I. 11.33 to 11.77) among females, and 4.91 (95% C.I. 4.75 to 5.07) among males. For hip fractures, the overall incidence rates were 3.23 (95% C.I. 3.11 to 3.34) among females and 1.21 (95% C.I. 1.12 to 1.28) among males, respectively. Advanced age, history of fracture, use of corticosteroids, rheumatoid arthritis, BMI
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- 2012
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397. Biological treatments in Behçet's disease: beyond anti-TNF therapy
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Caso, Francesco, Costa, Luisa, Rigante, Donato, Lucherini, Orso Maria, Caso, Paolo, Bascherini, Vittoria, Frediani, Bruno, Cimaz, Rolando, Marrani, Edoardo, Nieves-Martín, Laura, Atteno, Mariangela, Raffaele, Carmela G L, Tarantino, Giusyda, Galeazzi, Mauro, Punzi, Leonardo, Cantarini, Luca, [Caso,F, Lucherini,OM, Bascherini,V, Frediani,B, Nieves-Martin,L, Galeaxxi,M, Cantarini,L] Interdepartmental Research Center of Systemic Autoimmune and Autoinflammatory Diseases, Rheumatology Unit, Policlinico Le Scotte, University of Siena, Siena, Italy. [Caso,F, Punzi,L] Rheumatology Unit, Department of Medicine DIMED, University of Padova, Padova, Italy. [Costa,L, Atteno, M] Rheumatology Unit, Department of Clinical Medicine and Surgery, University Federico II, Naples, Italy. [Rigante,D, Raffaele,CGL, Tarantino,G] Institute of Pediatrics, Cattolica Sacro Cuore University, Rome, Italy. [Caso,P] La Sapienza University, Rome, Italy. [Cimaz,R, Marrani,E] Department of Pediatrics, Rheumatology Unit, Anna Meyer Children’s Hospital and University of Florence, Florence, Italy. [Nieves-Martín,L] Rheumatology Service, Hospital Regional Universitario Carlos Haya, University of Màlaga, Màlaga, Spain., and Novartis, SOBI.
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Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Globulins::Serum Globulins::Immunoglobulins::Antibodies::Antibodies, Monoclonal::Antibodies, Monoclonal, Murine-Derived [Medical Subject Headings] ,Anticuerpos monoclonales humanizados ,Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Globulins::Serum Globulins::Immunoglobulins::Antibodies::Antibodies, Monoclonal [Medical Subject Headings] ,Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Globulins::Serum Globulins::Immunoglobulins::Antibodies::Antibodies, Monoclonal::Antibodies, Monoclonal, Humanized [Medical Subject Headings] ,Chemicals and Drugs::Biological Factors::Intercellular Signaling Peptides and Proteins::Cytokines::Interleukins::Interleukin-6 [Medical Subject Headings] ,Interleucina-6 ,Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] ,Chemicals and Drugs::Biological Factors::Intercellular Signaling Peptides and Proteins::Tumor Necrosis Factors::Tumor Necrosis Factor-alpha [Medical Subject Headings] ,Interleucina-1beta ,Diseases::Skin and Connective Tissue Diseases::Skin Diseases::Skin Diseases, Vascular::Behcet Syndrome [Medical Subject Headings] ,Interleucina 1 ,Factor necrosis tumoral alfa ,Chemicals and Drugs::Biological Factors::Intercellular Signaling Peptides and Proteins::Cytokines::Interleukins::Interleukin-1 [Medical Subject Headings] ,Chemicals and Drugs::Biological Factors::Intercellular Signaling Peptides and Proteins::Cytokines::Interleukins::Interleukin-1::Interleukin-1beta [Medical Subject Headings] ,Síndrome de behçet - Abstract
Journal Article; Review; Behçet's disease (BD) is universally recognized as a multisystemic inflammatory disease of unknown etiology with chronic course and unpredictable exacerbations: its clinical spectrum varies from pure vasculitic manifestations with thrombotic complications to protean inflammatory involvement of multiple organs and tissues. Treatment has been revolutionized by the progressed knowledge in the pathogenetic mechanisms of BD, involving dysfunction and oversecretion of multiple proinflammatory molecules, chiefly tumor necrosis factor- (TNF-) α, interleukin- (IL-) 1β, and IL-6. However, although biological treatment with anti-TNF-α agents has been largely demonstrated to be effective in BD, not all patients are definite responders, and this beneficial response might drop off over time. Therefore, additional therapies for a subset of refractory patients with BD are inevitably needed. Different agents targeting various cytokines and their receptors or cell surface molecules have been studied: the IL-1 receptor has been targeted by anakinra, the IL-1 by canakinumab and gevokizumab, the IL-6 receptor by tocilizumab, the IL12/23 receptor by ustekinumab, and the B-lymphocyte antigen CD-20 by rituximab. The aim of this review is to summarize all current experiences and the most recent evidence regarding these novel approaches with biological drugs other than TNF-α blockers in BD, providing a valuable addition to the actually available therapeutic armamentarium. Yes
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- 2014
398. The labyrinth of autoinflammatory disorders: a snapshot on the activity of a third-level center in Italy
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Antonio Vitale, Orso Maria Lucherini, Caterina De Clemente, Luisa Costa, Flora Magnotti, Giacomo Emmi, Eugenia Prinzi, Maria Cristina Maggio, Luca Cantarini, Mauro Galeazzi, Donato Rigante, Bruno Frediani, Elena Silvestri, Giuseppe Lopalco, Francesco Caso, Rolando Cimaz, Cantarini, Luca, Vitale, Antonio, Lucherini, Orso Maria, De Clemente, Caterina, Caso, Francesco, Costa, Luisa, Emmi, Giacomo, Silvestri, Elena, Magnotti, Flora, Maggio, Maria Cristina, Prinzi, Eugenia, Lopalco, Giuseppe, Frediani, Bruno, Cimaz, Rolando, Galeazzi, Mauro, Rigante, Donato, Cantarini, L., Vitale, A., Lucherini, O.M., De Clemente, C., Caso, F., Costa, L., Emmi, G., Silvestri, E., Magnotti, F., Maggio, M.C., Prinzi, E., Lopalco, G., Frediani, B., Cimaz, R., Galeazzi, M., and Rigante, D.
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Adult ,medicine.medical_specialty ,Referral ,Proinflammatory cytokine ,Diagnosis, Differential ,Rheumatology ,Acquired immunodeficiency syndrome (AIDS) ,Internal medicine ,Periodic fever ,Medicine ,Humans ,Age Factor ,Child ,Genetic disorder ,Innate immune system ,business.industry ,Hereditary Autoinflammatory Diseases ,Age Factors ,General Medicine ,medicine.disease ,Adulthood ,Interleukin-1β ,Immunity, Innate ,Hereditary Autoinflammatory Disease ,Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA ,Italy ,Recurrent fever ,Immunology ,Autoinflammation ,business ,Autoinflammatory Disorders ,Human - Abstract
Autoinflammatory disorders (AIDs) are a novel class of diseases elicited by mutations in genes regulating the homeostasis of innate immune complexes, named inflammasomes, which lead to uncontrolled oversecretion of the proinflammatory cytokine interleukin-1β. Protean inflammatory symptoms are variably associated with periodic fever, depicting multiple specific conditions. Childhood is usually the lifetime in which most hereditary AIDs start, though still a relevant number of patients may experience a delayed disease onset and receive a definite diagnosis during adulthood. As a major referral laboratory for patients with recurrent fevers, we have tested samples from 787 patients in the period September 2007–March 2014, with a total of 1,328 AID-related genes evaluated and a gene/patient ratio of 1.69. In this report, we describe our experience in the clinical approach to AIDs, highlight the most striking differences between child and adult-onset AIDs, and shed an eye-opening insight into their diagnostic process.
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- 2014
399. Monogenic autoinflammatory syndromes: state of the art on genetic, clinical, and therapeutic issues
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Mauro Galeazzi, Bruno Frediani, Orso Maria Lucherini, Adele Compagnone, Mariangela Atteno, Paolo Caso, Luca Cantarini, Luisa Costa, Francesco Caso, Donato Rigante, Antonio Vitale, Leonardo Punzi, Caso, Francesco, Rigante, D, Vitale, A, Lucherini, Om, Costa, Luisa, Atteno, M, Compagnone, A, Caso, P, Frediani, B, Galeazzi, M, Punzi, L, and Cantarini, L.
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Pathology ,medicine.medical_specialty ,lcsh:Diseases of the musculoskeletal system ,Mevalonate kinase deficiency ,Majeed syndrome ,business.industry ,Immunology ,Familial Mediterranean fever ,Inflammasome ,PAPA syndrome ,Review Article ,medicine.disease ,Serous fluid ,Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA ,Rheumatology ,Autoinflammation ,medicine ,Sarcoidosis ,lcsh:RC925-935 ,business ,Blau syndrome ,medicine.drug - Abstract
Monogenic autoinflammatory syndromes (MAISs) are caused by innate immune system dysregulation leading to aberrant inflammasome activation and episodes of fever and involvement of skin, serous membranes, eyes, joints, gastrointestinal tract, and nervous system, predominantly with a childhood onset. To date, there are twelve known MAISs: familial Mediterranean fever, tumor necrosis factor receptor-associated periodic syndrome, familial cold urticaria syndrome, Muckle-Wells syndrome, CINCA syndrome, mevalonate kinase deficiency, NLRP12-associated autoinflammatory disorder, Blau syndrome, early-onset sarcoidosis, PAPA syndrome, Majeed syndrome, and deficiency of the interleukin-1 receptor antagonist. Each of these conditions may manifest itself with more or less severe inflammatory symptoms of variable duration and frequency, associated with findings of increased inflammatory parameters in laboratory investigation. The purpose of this paper is to describe the main genetic, clinical, and therapeutic aspects of MAISs and their most recent classification with the ultimate goal of increasing awareness of autoinflammation among various internal medicine specialists.
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- 2013
400. Italian society for Rheumatology recommendations for the management of hand osteoarthritis
- Author
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M. Matucci Cerinic, M. Manara, Bruno Frediani, M. Ceruso, P. Richelmi, G. A. Checchia, A. Lombardi, Gianfilippo Bagnato, Alessandra Bortoluzzi, I. Prevete, Carlo Alberto Scirè, G. D'Avola, Roberta Ramonda, Leonardo Punzi, G. Di Giacinto, Giovanni Minisola, Gerolamo Bianchi, F. Torretta, G. Mascheroni, Alberto Migliore, M. Scarpellini, A. Mannoni, Marta Favero, Manara, M, Bortoluzzi, A, Favero, M, Prevete, I, Scire', C, Bagnato, G, Bianchi, G, Ceruso, M, Checchia, G, D'Avola, G, Di Giacinto, G, Frediani, B, Lombardi, A, Mannoni, A, Mascheroni, G, Matucci Cerinic, M, Punzi, L, Richelmi, P, Scarpellini, M, Torretta, F, Migliore, A, Ramonda, R, and Minisola, G
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musculoskeletal diseases ,lcsh:Internal medicine ,medicine.medical_specialty ,Hand Joint ,Evidence-based practice ,Hand Joints ,Alternative medicine ,MEDLINE ,lcsh:Medicine ,Context (language use) ,Recommendations ,NO ,Rheumatology ,Internal medicine ,Hand osteoarthritis ,Osteoarthritis ,medicine ,Humans ,Treatment ,Hand osteoarthriti ,lcsh:RC31-1245 ,business.industry ,lcsh:R ,Recommendation ,Clinical Practice ,Physical therapy ,Osteoarthriti ,business ,Hand osteoarthritis, Treatment, Recommendations ,Systematic search ,Human - Abstract
Hand osteoarthritis (OA) is a common and potentially disabling disease, with different features from hip and knee OA so that a specific therapeutic approach is required. Evidence based recommendations for the management of hand OA were developed by the European League Against Rheumatism (EULAR) in 2006. The Italian Society for Rheumatology (SIR) aimed to update, adapt to national contest and disseminate the EULAR recommendations for the management of hand OA. The multidisciplinary group of experts included specialists involved in the management of patients with hand OA. In order to maintain consistency with EULAR recommendations, a similar methodology was utilized by the Italian group. The original propositions were reformulated in terms of a search query and for every recommendation a systematic search was conducted updating EULAR recommendations’ review. The propositions were translated in Italian and reformulated basing on collected evidences and expert opinion. The strength of recommendation was measured for each proposition with the EULAR ordinal and visual analogue scales. The original 11 propositions of EULAR recommendations were translated and adapted to Italian context. Further evidences were collected about non-pharmacological therapies, local treatments, intra-articular injection with SYSADOA and corticosteroids, and surgery. The SIR has developed updated recommendations for the management of hand OA adapted to the Italian healthcare system. Their implementation in clinical practice is expected to improve the management of patients with hand OA.
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- 2013
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