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    Synovial inflammation and associated intra-articular pathology in a cohort of patients undergoing anterior cruciate ligament reconstruction for traumatic rupture

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    Purpose: Previous epidemiologic studies have established that there is a strong relationship between anterior cruciate ligament (ACL) disruption and the risk for subsequent development of osteoarthritis (OA). Though not normally considered a classical inflammatory arthropathy, OA is often associated with low-grade synovitis. In patients with OA, synovial inflammation is one factor associated with risk of progression of structural joint deterioration and symptoms. The aims of the study were to characterize the histopathological features and chemokine profile of the synovium in patients undergoing ACL reconstruction after traumatic ACL rupture and to determine the relationship between the synovial characteristics and meniscal and/or cartilage abnormalities. Materials and Methods: The study was conducted in the context of the ACL registry at the Hospital for Special Surgery (HSS), New York, USA, which maintains extensive records of preclinical, intraoperative and post-operative data for 1200 patients who have undergone ACL reconstruction for traumatic ACL rupture. Synovial biopsies were collected from 40 patients during arthroscopic surgery and processed for histology and RNA extraction. Synovial features of inflammation and degeneration were assessed using a combination histological synovial scoring system developed at HSS in which the following six features were graded: perivascular mononuclear cell infiltration, detritus, mucoid change, fibrosis, increased vascularity and hyperplasia of the synovial lining layer, leading to a total combined maximal score of 15. The following clinical data were also collected: age, sex, body mass index (BMI), date of injury, time to surgery and the intraoperative presence or absence of meniscal and/or cartilage abnormalities. Total RNA extracts were prepared from the suprapatellar synovial samples and the levels of mRNA for four chemokines (IL-8, CCL19, CCL21, and CCL5) and one chemokine receptor (CCR7), shown previously to be associated with synovial inflammation in patients undergoing meniscectomy by microarray pathway analysis (C Scanzello, Arthritis Rheum 2011) [1], were measured by real-time qPCR. Results: Of the 40 patients undergoing synovial biopsy and analysis, 19 were female and 21 male, with median ages of 20 and 36, respectively. 85% of the patients exhibited histological evidence of synovial inflammation or degeneration in the suprapatellar area: 44.1% of patients scored 1 or 2, 44.1% scored 3 or 4, 5.8% scored 5 or 6, and 5.8% scored 7 or 8. Arthroscopically, meniscal abnormalities (mostly tears) were observed in 19/40 patients (47%), and cartilage defects were observed in 16/40 patients (40%). No association was observed between the body mass index (BMI), date of injury, time to surgery, and frequency of cartilage defects or meniscal pathology. The patients were divided in two groups based on age: 19 of patients older than 30 years and 21 patients younger than 30 years. Meniscal tears were associated with synovial inflammation in patients older than 30 years. We selected 16 synovial suprapatellar biopsies from patients > 30 years for qPCR analysis, 8 from patients without synovial inflammation (grade 0-2) and 8 with synovial inflammation (grade 3-8). The levels of CCL5 and CCL19 mRNA were significantly upregulated in biopsy specimens exhibiting inflammation with associated fold-changes of 2.7 (P=0.0426) and 4.7 (P=0.0289), respectively. Conclusions: In our study, we observed a high percentage of low-grade synovitis (85%), meniscal tear (47%), and/or cartilage defects (40%) in patients undergoing ACL reconstruction for traumatic ACL rupture. In a cohort of patients > 30-years-old, the presence of synovitis correlated with evidence of a meniscal tear, suggesting a relationship between these two pathologic processes. Preliminary analysis of mRNA expression patterns in this group of patients confirmed the upregulation of CCL5 and CCL19. This is in agreement with previously published data [1]. These two chemokines may play an important contributory role in the pathophysiology of OA particularly in those patients having synovial inflammationScopo dello studio: I dati riportati in lettura evidenziano una stretta correlazione tra la rottura del legamento crociato anteriore (LCA) e il rischio di sviluppare osteoartrosi (OA). Benché non sia considerata una classica artropatia infiammatoria, l’OA è spesso associata alla presenza di sinovite di basso grado. Nei pazienti affetti da OA, l’infiammazione sinoviale viene considerata un fattore di rischio correlato con l’attività di malattia e con la progressione del danno articolare. Lo scopo dello studio consiste nel caratterizzare la sinovite dei pazienti sottoposti a ricostruzione del LCA post rottura traumatica e nell’identificare la correlazione tra la presenza d’infiammazione sinoviale e la coesistenza di lesioni meniscali e cartilaginee. Materiali e Metodi: Lo studio è stato condotto presso l’Hospital for Special Surgery (HSS) di New York, USA, utilizzando il registro per il LCA, che raccoglie i dati clinici, preoperatori ed intraoperatori, di 1200 pazienti sottoposti a ricostruzione del LCA in seguito a rottura traumatica. Su 40 pazienti sono state eseguite biopsie sinoviali in corso di artroscopia ed i campioni raccolti sono stati sottoposti ad istologia e ad estrazione di RNA. La presenza d’infiammazione sinoviale è stata valutata mediante l’utilizzo di uno score istologico composito messo a punto all’HSS. Tale score prende in considerazione la presenza dei seguenti parametri istologici per un punteggio complessivo massimo di 15: infiltrazione perivascolare di cellule mononucleate, detriti, cambiamenti mucoidi, fibrosi, incremento della vascolarizzazione ed iperplasia della membrana sinoviale. Sono stati inoltre raccolti i seguenti dati clinici: età, sesso, indice di massa corporea (BMI), data del trauma, data dell’intervento chirurgico e riscontro intraoperatorio di lesioni meniscali e/o cartilaginee. I livelli di mRNA di 4 chemochine (IL-8, CCL19, CCL21, and CCL5) e di un recettore per le chemochine (CCR7) sono stati misurati sulla sinovia sovrapatellare, tramite real time qPCR. Tali chemochine sono risultate precedentemente associate all’infiammazione sinoviale nei pazienti sottoposti a meniscectomia in uno studio condotto tramite microarray analisi (C Scanzello, Arthritis Rheum 2011) [1]. Risultati: Dei 40 pazienti sottoposti a biopsia sinoviale, 19 sono femmine e 21 maschi, con un’età mediana rispettivamente di 20 e 36 anni. L’85% dei pazienti analizzati presenta segni istologici d’infiammazione sinoviale a livello sovrapatellare: il 44.1% dei pazienti ha uno score tra 1 e 2, il 44.1% uno score tra 3 e 4, il 5.8% score tra 5 e 6, e il 5.8% uno score tra 7 e 8. Durante l’artroscopia si sono riscontrate lesioni meniscali in19/40 pazienti (47%) e cartilaginee in 16/40 pazienti (40%). Non si sono identificate correlazioni tra grado d’infiammazione sinoviale e BMI, data del trauma, data dell’intervento e frequenza delle lesioni meniscali e cartilaginee. A seconda dell’età si è suddiviso i pazienti in due gruppi: 19 pazienti hanno un’età superiore a 30 anni e 21 un’età inferiore ai 30 anni. La presenza di lesioni meniscali è associata all’infiammazione sinoviale nei pazienti con età > 30 anni. Tra le biopsie sinoviali sovrapatellari eseguite su pazienti con età > 30 anni, se ne sono selezionate 16 da sottoporre a qPCR analisi: 8 biopsie provenienti da pazienti senza segni d’infiammazione sinoviale (grado 0-2) e 8 provenienti da pazienti con infiammazione sinoviale (grado 3-8). I livelli di mRNA di CCL5 e CCL19 risultano significativamente più elevati nei pazienti con infiammazione sinoviale di 2.7 (p = 0.0426) e di 4.7 volte (p =0.0289) rispettivamente. Conclusioni: Nel nostro studio, i pazienti sottoposti a ricostruzione del LCA per rottura traumatica presentano un’alta percentuale di sinovite di basso grado (85%), lesioni meniscali (47%) e difetti cartilaginei (40%). Nel gruppo di pazienti con età > 30 anni, la presenza di sinovite si correla con il riscontro di lesioni meniscali suggerendo una possibile relazione tra i due processi patologici. L’analisi dell’espressione dell’mRNA in questo gruppo di pazienti, ha confermato un incremento di CCL5 and CCL19, in accordo con quanto riportato in letteratura [1]. Queste due chemochine potrebbero avere un ruolo chiave nella patofisiologia dell’OA, in particolar modo nei pazienti con infiammazione sinovial

    Rheumatoid arthritis is the major risk factor for septic arthritis in rheumatological settings

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    Septic arthritis (SA) is a clinical emergency with considerable morbidity and mortality that can lead to rapid joint destruction and irreversible functional loss. The reported incidence varies from 2-5 cases/100,000 person-years in the general population to 70 cases/100,000 person-years among patients with rheumatoid arthritis. In fact, individuals with rheumatoid arthritis are at particular risk for developing SA. This may be due to several reasons: joint disease predisposes to bacterial joint colonization and RA itself and its treatment with corticosteroids, disease-modifying antirheumatic drugs (DMARDs) and biological therapies may decrease the immune function required for protection from pathogens. Steroids and DMARDs seem to affect the leukocyte synovial count; indeed, RA patients with SA have a leukocyte count in synovial fluid (SF) lower than patients with SA without underlying rheumatic diseases. The diagnosis of SA in RA patients can be difficult because the development of a hot painful joint is often confused with a relapse of the underlying joint disease leading to delay in diagnosis. For this reason the microscopic analysis and culture of synovial fluid are crucial to exclude septic arthritis

    Erosive Hand Osteoarthritis: Recent Advances and Future Treatments

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    Purpose of the Review: Erosive hand osteoarthritis (EHOA) is an aggressive form of hand osteoarthritis that leads to significant disability, and recent data suggests that it is increasing in prevalence. This review provides an update of our current understanding of epidemiology, genetic associations, biomarkers, pathogenesis, and treatment of EHOA, with particular focus on studies published within the last 5 years. Recent Findings: New studies of EHOA have identified new genetic loci associated with disease, including variants in genes involved in inflammation and bone remodeling. Preclinical studies implicate pathways of innate immunity, including some that may be causal in the condition. Recent novel studies showed that inflammatory features identified by ultrasound and MRI are associated with development of erosive lesions over time on conventional radiography. In the future, these imaging modalities may be useful in identifying patients at risk of adverse outcomes. Summary: Promising new findings in genetics, biomarkers, and treatment targets will hopefully allow for future therapeutic options for this debilitating condition

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis

    Dispelling the Myths Behind First-author Citation Counts

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    We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more sophisticated methods
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