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Background:SAPHO syndrome is a rare autoinflammatory disease characterized in children by chronic non-bacterial osteitis (CNO), associated to a heterogenous dermatological involvement, ranging from Palmo-plantar pustulosis (PPP), to psoriasis vulgaris (PV), acne, hidradenitis suppurativa (HS), and pyoderma gangrenosum (PG). A recent study [1] suggested the existence of two different disease clusters in pediatric SAPHO syndrome (pSAPHO) based on skin manifestations: an acne-HS-PG group (male prevalence and disease onset in puberal age with skin manifestations refractory to multiple treatments) and a PPP-PV group (female prevalence and disease onset in prepuberal age with osteoarticular manifestations).Objectives:to confirm the presence of different disease clusters of pSAPHO in an italian multicentric cohort of patients, and to evaluate the efficacy of the different treatments in pSAPHO syndrome, compared to CNO.Methods:SAPHO patients were enrolled in the Eurofever Registry and the data retrospectively analysed. Patients with pSAPHO were divided into an acne-HS-PG group and a PPP-PV group, and were compared to a CNO group without skin manifestations. Comparison of frequencies between groups was performed by the means of the Chi-square test or by the Fischer’s Exact test.Results:43 pSAPHO patients with skin manifestations (32 acne-HS-PG and 11 PPP-PV) were enrolled and compared to 50 CNO. In the Acne-HS-PG group, 83.9% of the patients were males, with disease onset in puberal age with skin manifestations (median 13.7 years), and the appearance of osteoarticular symptoms in the following year in 81% of patients. In the PPP-PV group, 90.9% of patients were females, with disease onset in 100% of patients with osteoarticular manifestations in prepuberal years (median 10 years), and with the appearance of skin manifestations in the following year. In the CNO group there were no gender differences, with a median age at disease onset of 9.2 years. A statistically significant difference was found between the 3 groups in terms of sex (p< 0.0001), and between acne-HS-PG and PPP-PV and acne-Hs-PG and CNO for the age at disease onset (p< 0.0001) (Figure 1A). Moreover, a different osteoarticular involvement was evident in the 3 groups: all patients showed typical metaphyseal involvement, even if it was prevalent in the CNO group (86%, p=0.04), while an axial pattern (sterno-clavicular-spine-sacroiliacs) was more frequently present in the acne-HS-PG group (p<0.01), and a mandibular involvement in the PPP-PV group (p<0.01) (Figure 1b). The 3 groups presented also a different response to treatments: in the CNO group, NSAIDs, methotrexate and salazopyrin were more frequently used (p<0.05), and were efficacious in about 40% of patients, while 36% required bisphosphonates (BP), and 28% a biologic therapy. Similarly, in the PPP-PV group 30% of patients responded to NSAIDs alone, 30% to BP while 30% required the addition of a biological therapy. The skin responded well to the topical therapies or to DMARDs. In the acne-HS-PG group instead, there was a prevalent use of systemic steroids (50% of patients, p<0.05) and biological therapies (81% of patients, p<0.05). Among these, the combination Adalimumab/methotrexate was the more efficacious, with a remission achieved in 53% of patients. The skin resulted particularly difficult to treat in all the patients and was the cause of a therapy cycling.Conclusion:This study confirms the presence of 2 different disease clusters in pSAPHO based on the skin manifestations: an acne-HS-PG group characterized by a male predominance with puberal disease onset with skin manifestations particularly refractory to treatments, and a PPP-PV group characterized by female predominance with prepuberal disease onset with osteoarticular manifestations. These findings warrant a different therapeutical approach based on skin manifestations, and highlight the need of a new disease classification.REFERENCES:[1] Matucci-Cerinic C, et al. Semin Arthritis Rheum. 2023 Dec;63:152277.Figure 1.Acknowledgements:NIL.Disclosure of Interests:Caterina Matucci-Cerinic: None declared, Anna Attico: None declared, Clara Malattia: None declared, Alessandro Consolaro: None declared, Silvia Rosina: None declared, Luciana Breda: None declared, Saverio La Bella: None declared, Marco Cattalini: None declared, Francesca Ricci: None declared, Giovanni Conti: None declared, Adele Civino: None declared, Francesco Licciardi: None declared, Letizia Baldini: None declared, Antonella Insalaco: None declared, Francesco La Torre: None declared, Serena Pastore: None declared, Giovanni Filocamo: None declared, Gisella Beatrice Beretta: None declared, Gabriele Simonini: None declared, edoardo marrani: None declared, Angela Pistorio: None declared, Stefano Volpi SOBI, Roberta Caorsi: None declared, Nicolino Ruperto Abbvie, Aclaris, Amgen, AstraZeneca, Aurinia, BMS, Boehringer Ingelheim, Eli Lilly, Galapagos, Guidepoint, Janssen, Novartis, Pfizer, Sanofi., Abbvie, Aclaris, Amgen, AstraZeneca, Aurinia, BMS, Boehringer Ingelheim, Eli Lilly, Galapagos, Guidepoint, Janssen, Novartis, Pfizer, Sanofi., Gianmaria Viglizzo: None declared, Marco Gattorno Novartis, SOBI.

BackgroundSystemic juvenile idiopathic arthritis (sJIA) accounts up to 15 % of all patients with JIA and is distinct from the other disease categories due to the association of articular and extraarticular manifestations. The systemic Juvenile Arthritis Disease Activity Score (sJADAS) is a composite disease activity score validated specifically for use in sJIA that includes, beside the four components of the original JADAS, a fifth item aimed to quantify the burden of systemic features. The interpretation of scores on sJADAS requires criteria that identify the states of disease activity. These criteria can be used to monitor the disease course over time and to define therapeutic targets.ObjectivesTo compare the clinical and laboratory data of each disease activity state in patients enrolled in the multinational study aimed to define the sJADAS cutoffs.MethodsData were extracted from a multinational cross-sectional dataset that included patients diagnosed as sJIA by ILAR criteria, recruited between February 2022 and November 2022. At study visit, each patient was categorized subjectively by the caring physician into one of the following disease activity states: inactive disease (ID), low (or minimal) disease activity (LDA), moderate disease activity (MDA), or high disease activity (HDA). Study data was collected through a standard case report form and entered into an electronic database.ResultsA total of 231 patients were enrolled in 29 centers in 12 countries. The mean age at diagnosis was 5.63 years. 87 patients (37.7%) were judged as having ID, 39 (16.9%) LDA, 46 (19.9%) MDA and 59 (25.5%) HDA. The comparison of the main clinical and laboratory features across patients with the four disease activity states is shown in the Table 1. Overall, the presence of extraarticular manifestations was more common in patients with MDA and HDA (P<0.00001), whereas fever, rash, hepatosplenomegaly, and lymphadenopathy were more frequent in HDA patients (<0.00001). The count of active joints increased progressively from ID to HDA (p<0.00001). The mean values of physician global assessment of disease activity and systemic manifestations, as well as the mean values of acute phase reactants, were highest in patients with HDA, with gradual decrease from MDA to LDA to ID.ConclusionThis preliminary analysis of the study data indicates that the subjective assessment of disease state by the caring physicians led to discriminate reliably patients with different level of disease activity. This evaluation will, then, serve well as reference for the subsequent analyses aimed to identify the cutoffs for the main disease activity states in sJIA.Reference[1]Tibaldi J, Pistorio A, Aldera E, et al. Development and initial validation of a composite disease activity score for systemic juvenile idiopathic arthritis. Rheumatology (Oxford). 2020 Nov 1;59(11):3505-3514.Table 1.Comparison of clinical and laboratory features across disease activity states (n = 231). ID=inactive disease; LDA= low (or minimal) disease activity; MDA=moderate disease activity; HDA=high disease activity; MD global VAS=physician global assessment of disease activity; MD systemic VAS= physician global assessment of systemic disease activity; ESR= erythrocyte sedimentation rate; CRP= C-reactive protein; NAJ=Number of active joints.IDLDAMDAHDANumber of patients (n, %)87 (37.7)39 (16.9)46 (19.9)59 (25.5)Age at onset, years (mean, SD)6.17 (4.24)5.44 (3.06)5.11 (3.42)5.36 (4.06)MD global VAS (mean, SD)1.08 (2.64)2.5 (2.59)5.03 (2.59)6.61 (2.91)MD systemic VAS (mean, SD)0.06 (0.23)0.88 (1.13)3.08 (2.69)7.52 (2.17)Systemic features (n,%)1 (1.1)7 (17.9)22 (47.8)56 (94.9)• Fever0 (0)0 (0)19 (41.3)55 (93.2)• Rash0 (0)4 (10.3)9 (19.6)29 (49.2)• Hepatomegaly0 (00 (0)2 (4.3)21 (35.6)• Splenomegaly0 (0)1 (2.6)4 (8.7)14 (23.7)• Lymphadenopathy1 (1.1)2 (5.1)5 (10.9)20 (33.9)• Serositis0 (0)0 (0)4 (8.7)9 (15.3)ESR, mm/h (mean, SD)8.46 (7.63)16.26 (14.43)46.11 (34.53)66.85 (32.4)CRP, mg/dl (mean, SD)0.39 (0.85)0.88 (1.93)5.17 (7.03)7.89 (6.06)NAJ > 1 (%)1 (1.1)13 (33.3)34 (73.9)53 (89.8)AcknowledgementsThis work was partially supported by the Fundación Española de Reumatología (FER).Disclosure of InterestsAna Isabel Rebollo Giménez: None declared, Yulia Vyzhga: None declared, Luca Carlini: None declared, Silvia Rosina: None declared, Elisa Patrone: None declared, Maria Katsikas: None declared, Claudia Saad-Magalhaes: None declared, Dalia El-Ghoneimy: None declared, Yasser El Miedany: None declared, Raju Khubchandani: None declared, Priyankar Pal: None declared, Gabriele Simonini Grant/research support from: educational grants from Abbvie, Sobi, Novartis, Giovanni Filocamo Consultant of: consultancies from Sobi and Novartis, Maurizio Gattinara: None declared, Fabrizio De Benedetti: None declared, Davide Montin: None declared, Adele Civino: None declared, Motasem O. Alsuweiti: None declared, Valda Stanevicha: None declared, Vyacheslav Chasnyk: None declared, Ekaterina Alexeeva Speakers bureau: speakers bureaus for Roche, Novartis and Pfizer., Grant/research support from: research grants from Roche, Pfizer, Centocor, Eli Lilly, AbbVie, Bristol-Myers Squibb, MSD, Sanofi, Amgen and Novartis., SULAIMAN AL-MAYOUF Speakers bureau: speaker fees from Sobi and Novartis, Soamarat Vilaiyuk: None declared, Angelo Ravelli Speakers bureau: from:Abbvie, Angelini, Pfizer, Novartis, BMS, Reckitt Benckiser, Sobi, Alexion, Roche.

BackgroundChronic parenchymal lung disease (LD) is a new emerging severe life-threatening complication of sJIA. The number of sJIA patients with LD is apparently increasing and interestingly they are reported more frequently in North America. Data regarding frequency and features of sJIA-LD in Europe are not available.ObjectivesTo evaluate the burden of sJIA-LD in Europe.MethodsPatients with diagnosis of sJIA with LD, including pulmonary alveolar proteinosis (PAP), interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH), followed in European paediatric rheumatology centres were identified through a survey sent to the members of the MAS/SJIA Working Party.ResultsData from 34 sJIA-LD patients, diagnosed in 15 European paediatric rheumatology centres between 2007 and 2022, were collected. 33 patients were Caucasian and 1 was African-American; 21 were female. The median age at sJIA onset was 6 years and LD occurred after a median time of 2 years. 19 patients had a chronic persistent sJIA course, 14 had a polycyclic course and only 1 patient had a monocyclic course; 29 (85%) had active sJIA at time of LD diagnosis. During the disease course, 28 (82%) patients developed MAS, 12 (35%) of whom had MAS at sJIA onset and 19 (56%) had full-blown MAS at time of LD diagnosis; 23 (68%) patients had >1 MAS episode. 28 (82 %) patients were treated with at least one IL-1 or IL-6 inhibitor before LD diagnosis: 15 with canakinumab, 24 with anakinra and 13 with tocilizumab; 13 (38%) patients experienced drug adverse reaction to a cytokine inhibitor: 9 to tocilizumab and 4 to anakinra. 24 (70%) patients developed ILD, 6 (18%) PAP and 4 (12%) PAH. 15 (44%) patients presented acute digital clubbing; 16 (47%) patients developed hypoxia and 9 (26%) developed pulmonary hypertension. A chest CT scan was performed in all patients with evidence of septal thickening, peri-bronchovascular thickening and ground glass opacities in the majority of patients (26, 18 and 18 respectively). In 17 patients a bronchoalveolar lavage was performed and 12 underwent a lung biopsy. The histopathological pattern was alveolar proteinosis in 5 patients, endogenous lipoid pneumonia in 3, vasculitis in 1 and fibrosis in 1. Half of the patients (17) required ICU admission and 6 (18%) died. All the patients were treated with glucocorticoids (GCs) at time of diagnosis, and 26 received IL-1 or IL-6 inhibitor after the diagnosis (13 canakinumab, 20 anakinra, 14 tocilizumab).ConclusionLung involvement is an emerging life-threatening complication of sJIA and patients are also diagnosed in Europe. Prompt recognition is crucial and new therapeutic strategies are needed to reduce the risk and improve the outcome of this complication.References[1]Saper VE et al. Emergent high fatality lung disease in systemic juvenile arthritis. Ann Rheum Dis. 2019 Dec;78(12):1722-1731.[2]Schulert GS et al. Systemic Juvenile Idiopathic Arthritis-Associated Lung Disease: Characterization and Risk Factors. Arthritis Rheumatol. 2019 Nov;71(11):1943-1954.AcknowledgementsMAS/sJIA working party of Pediatric Rheumatology European Society.Disclosure of InterestsClaudia Bracaglia Speakers bureau: SOBI, Novartis, Consultant of: SOBI, Francesca Minoia Consultant of: SOBI, christoph kessel Speakers bureau: SOBI, Consultant of: Novartis, Grant/research support from: Novartis, Sebastian Vastert: None declared, Manuela Pardeo Consultant of: SOBI, Alessia Arduini: None declared, Özge Basaran: None declared, Nural Kiper: None declared, Mikhail Kostik: None declared, Mia Glerup: None declared, Sarka Fingerhutova: None declared, Roberta Caorsi Consultant of: SOBI, Novartis, AnnaCarin Horne: None declared, Giovanni Filocamo Consultant of: SOBI, Helmut Wittkowski: None declared, Marija Jelusic: None declared, Jordi Anton Speakers bureau: SOBI, Novimmune, Novartis, GSK, Pfizer., Consultant of: SOBI, Novimmune, Novartis, Pfizer, GSK, Grant/research support from: SOBI, Novimmune, Novartis, Abbvie, Pfizer, GSK, Roche, Amgen, Lilly, BMS, Sanofi, Samira Khaldi-Plassart: None declared, alexandre belot Consultant of: SOBI, Novartis, Roche, Pfizer., Gerd Horneff Speakers bureau: Abbvie, Chugai, Lilly, Sanofi, Novartis, Pfizer, Grant/research support from: MSD, Novartis, Roche, Seraina Palmer Sarott: None declared, Elvira Cannizzaro: None declared, Pavla Doležalová: None declared, Angelo Ravelli: None declared, Seza Ozen Speakers bureau: SOBI, Novartis, Consultant of: SOBI, Novartis, Fabrizio De Benedetti Consultant of: Abbvie, SOBI, Novimmune, Novartis, Roche, Pfizer.

The Lupus Foundation of America (LFA) convened an international working group to obtain a consensus definition of disease flare in lupus. With help from the Paediatric Rheumatology International Trials Organization (PRINTO), two web-based Delphi surveys of physicians were conducted. Subsequently, the LFA held a second consensus conference followed by a third Delphi survey to reach a community-wide agreement for flare definition. Sixty-nine of the 120 (57.5%) polled physicians responded to the first survey. Fifty-nine of the responses were available to draft 12 preliminary statements, which were circulated in the second survey. Eighty-seven of 118 (74%) physicians completed the second survey, with an agreement of 70% for 9/12 (75%) statements. During the second conference, three alternative flare definitions were consolidated and sent back to the international community. One hundred and sixteen of 146 (79.5%) responded, with agreement by 71/116 (61%) for the following definition: “A flare is a measurable increase in disease activity in one or more organ systems involving new or worse clinical signs and symptoms and/or laboratory measurements. It must be considered clinically significant by the assessor and usually there would be at least consideration of a change or an increase in treatment.” The LFA proposes this definition for lupus flare on the basis of its high face validity.

Background Juvenile idiopathic arthritis (JIA) is the most common pediatric chronic rheumatic disease, which requires constant follow-up over the years, due to relapses during its progression. To maintain a good quality of life, it is important to limit admissions as far as possible. With the development of a Diagnostic Therapeutic Assistance Pathway (DTAP), we aim to select patients with suitable clinical conditions to be moved from routine hospital management to day care or outpatient treatment, evaluating the number of patients to whom this would apply. Methods Monocentric study regarding admissions for JIA between 2014 and 2016 in a Pediatric Unit of a university hospital in Milan. Through an analysis of the medical records, relevant information was extracted and collected in a Microsoft™ Excel database; starting from the data collected during the first year, a DTAP was prepared for patients with active arthritis and appropriate clinical conditions. Results The study includes data from 223 JIA hospitalization cases involving 127 patients. Applying DTAP criteria, 32% patients would have avoided admissions and 23% would have been admitted less frequently. The data concerning the activities of the Unit for JIA patients showed a relevant drop in the number of hospitalizations since 2015, from 89 in 2014 to 66 and 68 in 2015 and 2016 respectively. Conclusion The opportunity offered by DTAP, has suggested feasible changes in hospitalization management and it’s use would promote the possibility of treating the children without hospitalization, or minimizing it. In conclusion DTAP application is a priority for the continuous improvement of clinical practice and quality of life for patients and their families.

BackgroundUltrasound (US) is a powerful tool for the assessment of joint disease in children with juvenile idiopathic arthritis (JIA) and it may provide additional information about disease activity and response to therapy in JIA patients. In 2009, the first composite disease activity score for JIA, named the Juvenile Arthritis Disease Activity Score (JADAS), was published (1). This tool includes the following 4 variables: 1) physician global assessment of overall disease activity (PG); 2) parent/patient global assessment of well being (WB); 3) count of joints with active arthritis; and 4) ESR, normalised to a 0–10 scale. The correlation between US findings and the principal variables of disease activity in JIA remains to be established.ObjectivesTo evaluate the correlation between US findings and the parent's assessment of pain and WB, the PG and ESR.MethodsBefore the study visit, parents of children with JIA were asked to complete the Juvenile Arthritis Multidimensional Assessment Report (JAMAR), which includes a standardized assessment of pain and WB on a 21-numbered circle visual analog scales (VAS), and several other parent centered JIA outcome measures. At study visit, a pediatric rheumatologist, who was unaware of parent's reports, performed a formal joint assessment and scored the PG on 21-numbered circle VAS. After the visit, a pediatric radiologist with almost 10 years of experience in US assessment in JIA, valuated independently the presence of synovial hypertrophy/effusion (gray scale US - GSUS) and Power Doppler (PDUS) in metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints, knees and ankles, and quantified each US feature on a 0-3 semiquantitative scale. In each patient, the Juvenile Arthritis Disease Activity Score (JADAS) 10 was calculated. The correlations between parent pain and WB, PG and ESR were assessed using Spearman's rank correlation. Correlations were considered high if 0.7, moderate if 0.4–0.7, and low if <0.4ResultsThe JAMAR was completed by parents of 28 unselected patients, 17 with persistent oligoarthritis, 4 with extended oligoarthritis, 6 with rheumatoid factor-negative polyarthritis, 1 with systemic arthritis; aged between 5 months and 21 years. The median (range) of JADAS 10 was 13 (0-30.8).The table shows the correlation between US score with the variables considered.US Gray scaleUSGS - elbowUSGS - wristUSGS - MCPUSGS - PIPUSGS - kneeUSGS - ankleVAS WB0,440,420,520,550,220,20VAS pain0,540,430,500,560,220,13VAS GA0,390,280,330,430,280,00ESR0,310,450,420,550,380,38US Power DopplerUSPD - elbowUSPD - wristUSPD - MCPUSPD - PIPUSPD - kneeUSPD - ankleVAS WB0,500,400,520,450,110,18VAS pain0,560,340,530,410,090,16VAS GA0,510,330,480,480,200,01ESR0,370,490,380,400,210,17ConclusionsThe results show, for upper extremities, moderate correlation between US findings and the measures of clinical assessment, and low correlation for knee and ankle, evidencing a major agreement of US with clinical variables in the assessment of disease activity in upper extremities compared with lowers. As expected, the correlation with ESR was overall lower.ReferencesConsolaro A, Ruperto N, Bazso A et al.: Development and validation of a composite disease activity score for juvenile idiopathic arthritis. Arthritis Rheum 2009; 61: 658-66.Disclosure of InterestNone declared

BackgroundAssessment of disease activity is a fundamental component of the clinical evaluation of children with Juvenile Idiopathic Arthritis (JIA) and the first composite disease activity score for JIA, the Juvenile Arthritis Disease Activity Score (JADAS), was reported.[1] Ultrasound (US) is a powerful tool for the assessment of joint disease and has been shown to be more accurate than clinical examination in detecting synovitis. However, the validity of Gray Scale US (GSUS) and Power Doppler US (PDUS) techniques for evaluating inflammatory activity in affected joints needs to be defined.ObjectivesTo develop and to investigate the construct validity of a composite disease activity index for JIA that includes US findings of synovitis compared with cJADAS in assessing joint inflammation.MethodsBefore the study visit, parents of children with JIA were asked to complete the Juvenile Arthritis Multidimensional Assessment Report (JAMAR), which includes a standardized assessment of pain and WB on a 21-numbered circle visual analog scales (VAS), and several other parent centered JIA outcome measures. At study visit, a pediatric rheumatologist, who was unaware of parent's reports, performed a formal joint assessment and scored the physician's global assessment (PG) on 21-numbered circle VAS. After the visit, a pediatric radiologist with almost 10 years of experience in US assessment in JIA, evaluated independently the presence or the absence of synovial hypertrophy/effusion (GSUS), and PDUS in elbows, wrists, metacarpophalangeal and interphalangeal joints, knees and ankles. The joints with hypertrophy/effusion at GSUS and positivity for PDUS was defined GSUS and PDUS active joints respectively. In each patient, the GSUS and the PDUS JADAS -10 were calculated as the sum of the scores of GSUS active joints and PDUS active joints to a maximum of 10 respectively, the parent WB, and the PG, which yields a global score between 0 to 30. The correlation between the number of active joints defined clinically, GSUS and PDUS active joints, the GSUS and PDUS JADAS-10 and the clinical JADAS-10 (2) was assessed using Spearman's rank correlation. Correlations were considered high if 0.7, moderate if 0.4–0.7, and low if <0.4.ResultsThe JAMAR was completed by parents of 28 unselected patients, 17 with persistent oligoarthritis, 4 with extended oligoarthritis, 6 with rheumatoid factor-negative polyarthritis, 1 with systemic arthritis; aged between 5 months and 21 years. The median (range) of cJADAS-10 (2) was 12.25 (0-26.5). The table shows the correlation between the the active joint count and the cJADAS 10 with the variables considered.Table 1Active joint count (up to 10)cJADAS10cJADAS100,71GSUS active (up to 10)0,660,61PDUS active (up to 10)0,650,80GSUS JADAS 100,560,92PDUS JADAS 100,510,92ConclusionsThe preliminary results of the construct validity of a composite disease activity score for JIA that encompasses ultrasound findings of synovitis, evidenced high correlation between the clinical JADAS 10 and US JADAS 10, both for GSUS and PDUS. The correlation between the active joint count defined clinically with the active joints evidenced by US was moderate.ReferencesConsolaro A et al. Development and validation of a composite disease activity score for juvenile idiopathic arthritis. Arthritis Rheum. 2009Consolaro A, et al. Arthritis Care Res 2014Disclosure of InterestNone declared

Histone deacetylases (HDACs) are a family of enzymes involved in the regulation of gene expression, DNA repair, and stress response. These processes often are altered in tumors, and HDAC inhibitors have had pronounced antitumor activity with promising results in clinical trials. Here, we report the crystal structure of human HDAC8 in complex with a hydroxamic acid inhibitor. Such a structure of a eukaryotic zinc-dependent HDAC has not be described previously. Similar to bacterial HDAC-like protein, HDAC8 folds in a single α/β domain. The inhibitor and the zinc-binding sites are similar in both proteins. However, significant differences are observed in the length and structure of the loops surrounding the active site, including the presence of two potassium ions in HDAC8 structure, one of which interacts with key catalytic residues. CD data suggest a direct role of potassium in the fold stabilization of HDAC8. Knockdown of HDAC8 by RNA interference inhibits growth of human lung, colon, and cervical cancer cell lines, highlighting the importance of this HDAC subtype for tumor cell proliferation. Our findings open the way for the design and development of selective inhibitors of HDAC8 as possible antitumor agents.

We discovered that the hepatitis C virus (HCV) envelope glycoprotein E2 binds to human hepatoma cell lines independently of the previously proposed HCV receptor CD81. Comparative binding studies using recombinant E2 from the most prevalent 1a and 1b genotypes revealed that E2 recognition by hepatoma cells is independent from the viral isolate, while E2–CD81 interaction is isolate specific. Binding of soluble E2 to human hepatoma cells was impaired by deletion of the hypervariable region 1 (HVR1), but the wild‐type phenotype was recovered by introducing a compensatory mutation reported previously to rescue infectivity of an HVR1‐deleted HCV infectious clone. We have identified the receptor responsible for E2 binding to human hepatic cells as the human scavenger receptor class B type I (SR‐BI). E2–SR‐BI interaction is very selective since neither mouse SR‐BI nor the closely related human scavenger receptor CD36, were able to bind E2. Finally, E2 recognition by SR‐BI was competed out in an isolate‐specific manner both on the hepatoma cell line and on the human SR‐BI‐transfected cell line by an anti‐HVR1 monoclonal antibody.

The ankle is one of the most commonly affected sites in juvenile idiopathic arthritis (JIA). This region has a complex anatomical structure owing to the presence of multiple joint recesses and surrounding tendons. While the prognostic value of ultrasound (US)-detected arthritis has been investigated in recent studies, the role of tenosynovitis in JIA remains still unexplored. To investigate: 1) US features of ankle involvement in JIA at disease onset; 2) the predictive value of US-detected tenosynovitis in ankles with clinically active disease of children with new-onset JIA. The clinical charts of all consecutive patients with new-onset JIA between May 2018 and January 2020 at study centres (Policlinico and G.Pini Hospitals of Milan) and with clinically active ankle disease among the joints affected were reviewed retrospectively. Data on ankle US assessment were retrieved and patients were then stratified as follows: 1) patients with detection on US of isolated arthritis in at least one of the joint recesses of the ankle region; 2) patients with detection on US of tenosynovitis in at least one of the tendon compartments of the ankle irrespective of the presence of concomitant arthritis. For each of these two categories, estimation of patients who were able to achieve clinical disease remission at 12 months since disease onset was evaluated. Twenty-seven new-onset JIA patients were found to have clinical involvement of the ankle among the joints affected. Nine of them (33.3%) showed on US isolated arthritis of the ankle, whereas US-detected tenosynovitis was found in 18 (66.7%) patients. The amount of patients who were able to achieve disease remission at 12-months was the same (66.7%) for both patients with and without US-detected tenosynovitis in the ankle (12/18 and 6/9 patients, respectively). In patients with US-detected tenosynovitis and clinical disease remission at 12 months, the lateral tendon compartment (LTC) was the tendon site more frequently affected by pathology (75.0%). Patients with US-detected tenosynovitis that did not achieve clinical disease remission at follow-up had the highest frequency of tendon pathology on US in the medial tendon compartment (MTC) (83.3%). The anterior tendon compartment was the less frequently affected tendon compartment of the ankle in all patients (33.3% in both patients with and without clinical remission of disease at the 12-months follow-up visit). US-detected tenosynovitis of the ankle is a common finding in patients with new-onset JIA with clinically ankle disease activity and is more frequent than the detection on US of isolated arthritis. The MTC and LTC are the tendon compartments more commonly affected on US. The detection on US of tenosynovitis at disease onset in ankles with clinical disease activity did not seem to affect the change to achieve the overall clinical disease remission compared to patients without tendon pathology but with joint disease in the ankle region. None declared