Minor head injury in anticoagulated patients: Outcomes and analysis of clinical predictors. A prospective study.

BACKGROUND: The optimal management of patients taking oral anticoagulants who experience minor head injury (MHI) is unclear. The availability of validated protocols and reliable predictors of prognosis would be of great benefit. We investigated clinical factors as predictors of clinical outcomes and intracranial injury (ICI). METHODS: We conducted a single-cohort, prospective, observational study in an ED. Our structured clinical pathway included a first head CT scan, 24 h observation and a second CT scan. The primary outcome was the occurrence of MHI-related death or re-admission to ED at day +30. The secondary outcome was the rate of delayed ICI (dICI), defined as second positive CT scan after a first negative CT scan. We assessed some clinical predictors derived from guidelines and clinical prediction rules as potential risk factors for the outcomes. RESULTS: 450 patients with a negative first CT scan who underwent a second CT scan composed our 'study population'. The rate of the primary outcome was 4%. The rate of the secondary outcome was 4.7%. Upon univariate and multivariate analysis no statistically significant predictors for the outcomes were found. CONCLUSIONS: Previous retrospective studies showed a lot of negative predictive factors for anticoagulated patients suffering a minor head injury. In our prospective study no clinical factors emerged as predictors of poor clinical outcomes and dICI. So, even if we confirmed a low rate of adverse outcomes, the best management of these patients in ED remains not so clear and future trials are needed.

Tocilizumab in COVID-19 interstitial pneumonia.

BACKGROUND: Published reports on tocilizumab in COVID-19 pneumonitis show conflicting results due to weak designs or heterogeneity in critical methodological issues. METHODS: This open-label trial, structured according to Simon's optimal design, aims to identify factors predicting which patients could benefit from anti-IL6 strategies and to enhance the design of unequivocal and reliable future randomized trials. A total of 46 patients with COVID-19 pneumonia needing of oxygen therapy to maintain SO2 > 93% and with recent worsening of lung function received a single infusion of tocilizumab. Clinical and biological markers were measured to test their predictive values. Primary end point was early and sustained clinical response. RESULTS: Twenty-one patients fulfilled pre-defined response criteria. Lower levels of IL-6 at 24 h after tocilizumab infusion (P = 0.049) and higher baseline values of PaO2/FiO2 (P = 0.008) predicted a favourable response. CONCLUSIONS: Objective clinical response rate overcame the pre-defined threshold of 30%. Efficacy of tocilizumab to improve respiratory function in patients selected according to our inclusion criteria warrants investigations in randomized trials.

Recommendations for the management of biofilm: a consensus document.

The potential impact of biofilm on healing in acute and chronic wounds is one of the most controversial current issues in wound care. A significant amount of laboratory-based research has been carried out on this topic, however, in 2013 the European Wound Management Association (EWMA) pointed out the lack of guidance for managing biofilms in clinical practice and solicited the need for guidelines and further clinical research. In response to this challenge, the Italian Nursing Wound Healing Society (AISLeC) initiated a project which aimed to achieve consensus among a multidisciplinary and multiprofessional international panel of experts to identify what could be considered part of 'good clinical practice' with respect to the recognition and management of biofilms in acute and chronic wounds. The group followed a systematic approach, developed by the GRADE working group, to define relevant questions and clinical recommendations raised in clinical practice. An independent librarian retrieved and screened approximately 2000 pertinent published papers to produce tables of levels of evidence. After a smaller focus group had a multistep structured discussion, and a formal voting process had been completed, ten therapeutic interventions were identified as being strongly recommendable for clinical practice, while another four recommendations were graded as being 'weak'. The panel subsequently formulated a preliminary statement (although with a weak grade of agreement): 'provided that other causes that prevent optimal wound healing have been ruled out, chronic wounds are chronically infected'. All members of the panel agreed that there is a paucity of reliable, well-conducted clinical trials which have produced clear evidence related to the effects of biofilm presence. In the meantime it was agreed that expert-based guidelines were needed to be developed for the recognition and management of biofilms in wounds and for the best design of future clinical trials. This is a fundamental and urgent task for both laboratory-based scientists and clinicians.

Psychometric properties of an index of three patient reported outcome (PRO) measures, termed the CLinical ARthritis Activity (PRO-CLARA) in patients with rheumatoid arthritis. The NEW INDICES study.

OBJECTIVES: To evaluate the psychometric properties of an index based on 3 patient reported outcomes measures, termed PRO-CLinical ARthritis Activity (PRO-CLARA), in order to facilitate rapid and easy rheumatoid arthritis (RA) activity assessment in daily routine. METHODS: 196 patients partially or not responding to disease modifying anti-rheumatic drugs (DMARDs), consented to participate in a multicentre cross-sectional study. For the evaluation of the psychometric properties of the PRO-CLARA, this population has been compared to another cohort of 247 outpatients with RA who were participating in a long-term observational study and who satisfying minimal disease activity and remission definitions. All patients completed the PRO-CLARA, combining patient's physical function, self-administered tender joint count and perception of global health status into a single measure of disease activity. Additional comparator composite indices were analysed. Internal consistency was assessed with Cronbach's alpha coefficient. A confirmatory factor analysis was carried out to test factor structure. Concurrent validity was analyzed using Spearman's correlations and cross-tabulations. Discriminant validity to distinguish patients with active and non-active disease was assessed with receiver operating characteristic (ROC) curve analysis. For agreement analysis, kappa statistics were calculated. RESULTS: In testing for internal consistency, we found that Cronbach's alpha for the PRO-CLARA was 0.893, indicating high reliability. PRO-CLARA proved to be significantly correlated to established RA activity assessment tools. The area under ROC curve of the PRO-CLARA gives identical results to those provided by other comparator indices. CONCLUSIONS: The study showed satisfactory psychometric properties of the PRO-CLARA.

Consolidation therapy for adult acute myeloid leukemia: a systematic analysis according to evidence based medicine.

Post-remission therapy in acute myeloid leukemia (AML) remains problematic. It has been demonstrated that younger patients can maintain longer complete remissions (CR) with aggressive post-remission therapies after induction treatment: allogeneic (allo), autologous (auto) stem cell transplantation (SCT), or intensive chemotherapy (ICC). The purpose of our study was to identify the most important randomized and controlled studies comparing these three therapeutic options, in order to draw conclusions and possible suggestions for post-remission therapy of AML, according to the evidence based medicine (EBM) rules. We performed an exhaustive analysis of the literature, searching either in electronic databases or among the references of the identified articles (hand searching). We searched the MEDLINE computer database for reports from 1985 through January 2005 and selected for analysis the clinical trials conducted over adults affected by newly diagnosed AML aged less than 65 years. The study design had to satisfy strict methodological criteria and must consider global mortality and/or disease free survival as primary outcomes. Overall we found 7750 papers; by using the limits "clinical trial" as publication type, "all adults 19+ years", we were able to select 344 papers. Among these, a further selection was made, based on two main clinical queries: 1) is auto-SCT superior to ICC/no other therapy in improving DFS and/or OS in adult AML patients in first CR? 2) is allo-SCT superior to auto-SCT/other therapeutic options in improving DFS and/or OS in adult AML patients in first CR? Concerning the first query, a possible advantage of auto-SCT over ICC was not clearly supported by data from clinical trials; there is no evidence that auto-SCT is superior in terms of OS to chemotherapy. Nevertheless, the reported TRM has been significantly reduced within the past years. Thus, the percentage of patients suitable for auto-SCT in CR has increased. Moreover, the scarce data concerning the comparison between auto-SCT and chemotherapy in different subsets of patients are unable to suggest a differentiated approach in patients with high-risk, standard-risk or low-risk AML. Data from the literature show that patients with unfavorable risk disease are more often addressed to allo-SCT and patients with low-risk disease receive more often intensive consolidation chemotherapy. Concerning the second query, interpretation of data from the main prospective studies about the role of allo-SCT in previously untreated AML is not easy. The first problem is the lack of real randomized clinical trials; in fact, according to the reported studies, AML patients generally receive allo-SCT on the basis of donor availability (the so called "genetic randomization"). The second problem is the frequent absence of intention to treat analysis. Despite methodological limitations, it was possible to compare allo-SCT with auto-SCT on a donor versus no-donor analysis and within risk groups. No overall benefit of allo-grafting on survival was demonstrated by any trial. In conclusion, the EBM approach highlighted the limitations observed in the published studies concerning consolidation therapy in AML; some suggestions, emerging from non-randomized, as well as randomized studies, are adequate, but not conclusive. This point, coupled with the intrinsic complexity to study AML biological heterogeneity, is probably a major obstacle to draw conclusive evidences for consolidation therapy in AML. These observations should plan to address new randomized studies on AML therapy; however, due to the emergence of genetic subgroups and new drugs targeting specific abnormalities, these trials should probably be designed directly focusing on the single entities. In this way, the cure of AML could eventually become the cure of each specific AML subset with its peculiar biological, molecular and prognostic features.

Hand surgery in rheumatoid arthritis: state of the art and suggestions for research.

OBJECTIVE: The role of surgery in the clinical management of patients with rheumatoid arthritis (RA)-associated hand dysfunction is still a subject of controversy. The efficacy of surgery in RA-associated hand dysfunction is assessed through an exhaustive review of published studies. METHODS: A high-sensitivity search strategy was used to identify in MedLine and CENTRAL original studies related to hand and wrist surgery in RA patients. We selected articles including at least two adult RA patients which evaluated clinical outcomes through an observational or experimental design. Eligible studies were evaluated by standardized criteria. Two investigators independently used a pre-defined form to extract data about patient population, intervention, follow-up and clinical outcomes. Disagreements were discussed and resolved. RESULTS: One hundred and ninety-six papers met inclusion criteria. Only five were randomized trials, while most studies followed an observational design, often of poor quality. As such, we could not pool data for statistical analysis; however, we were still able to provide a best evidence synthesis. A positive trend suggesting the efficacy of total carpal arthrodesis and metacarpophalangeal arthroplasty in reducing pain and improving function seemed to emerge from the published studies. CONCLUSIONS: Despite recent advances in medical treatment, surgery still plays a role in the clinical management of RA-associated hand dysfunction. However, the majority of the available studies showed methodological flaws that prevented a clear definition of both surgical indications and criteria for choosing any specific procedure. Suggestions for further investigations are also provided.

Are behaviour and motor performances of rheumatoid arthritis patients influenced by subclinical cognitive impairments? A clinical and neuroimaging study.

OBJECTIVE: To determine whether some behavioural manifestations and poor motor performances in patients affected by rheumatoid arthritis (RA) are due to subclinical cognitive defects. METHODS: We performed a psychometric assessment of 30 patients affected by RA exploring several cognitive domains such as memory, visual-spatial integration, motor planning, mental flexibility, relating performances with morphological and functional neuroimaging (MRI and SPECT). We also related the cognitive data with the Ritchie and Lee indexes and other clinical parameters. RESULTS: We found an impairment in visual-spatial tasks in 71% of patients with a high correlation to activity and disease severity as expressed by the Ritchie and Lee indexes (p < 0.005; p < 0.01). Furthermore, we detected in 38% of patients some difficulties in mental flexibility related to the Lee Index (p < 0.05). These poor performances are related to hypoperfusion of the frontal and parietal lobes as detected by brain SPECT; this finding is more evident in patients with brain white matter alterations on MRI. CONCLUSIONS: Our data allow us to hypothesize that manual dexterity could be due to a disconnection between subcortical white matter and parietal-frontal lobes because of microangiopathy; furthermore, a chronic reduction in sensorial stimuli by impaired joints could lead to produce an alteration in motor planning cognitive processes.

[Research and evaluation of Internet resources for the practice and teaching of nursing]. / Ricerca e valutazione delle risorse Internet per la pratica e l'insegnamento della professione infermieristica.

Recent changes in the Italian health care system are causing a complex redefinition of the traditional principles of nursing. Among the new principles that are being proposed, the implementation of a clinical practice based on the evidence generated by the medical research community appears to be prominent. However, objective time constraints in finding and evaluating the available information have often hampered the achievement of this highly desirable goal. In this perspective, exploitation of the intrinsic quickness of the internet-based information retrieval systems has the potential to effectively circumvent the problem. To provide nurses with a proper training in a timely search and evaluation of on-line data, we have designed and developed a guide to those websites providing clinical information. This guide consists of (1) reviews of existing websites, and (2) proposal of a standardized model for selection, evaluation, and description of existing and newly appearing websites. We believe that this guide might increase the capability of nurses to effectively exploit the medical and scientific information resources available on the net.

Expression and production of the long pentraxin PTX3 in rheumatoid arthritis (RA).

PTX3 is a secreted molecule which consists of a C-terminal domain similar to classical pentraxins (e.g. C-reactive protein (CRP)) and of an unrelated N-terminal domain. Unlike the classical pentraxins, the long pentraxin PTX3 is expressed in response to IL-1beta and tumour necrosis factor-alpha (TNF-alpha), but not to IL-6, in various cell types. The present study was designed to investigate the expression of PTX3 in RA. Dissociated RA and osteoarthritis (OA) type B synoviocytes were cultured in the presence and in the absence of inflammatory cytokines. PTX3 mRNA expression in synoviocytes was evaluated by Northern analysis. PTX3 protein levels in synovial cell cultures and synovial fluid were estimated by ELISA, and PTX3 distribution in synovial tissues by immunohistochemical techniques. OA synoviocytes were induced to express high levels of PTX3 mRNA by TNF-alpha, but not by other cytokines including IL-1beta and IL-6. RA synoviocytes, unlike OA synoviocytes, constitutively expressed high levels of PTX3 in the absence of deliberate stimulation. The constitutive expression of PTX3 in RA synoviocytes was not modified by anti-TNF-alpha antibodies, IL-1 receptor antagonist or a combination of the two agents. In contrast, interferon-gamma and transforming growth factor-beta inhibited PTX3 constitutive expression in RA synoviocytes. The joint fluid from RA patients contained higher levels of immunoreactive PTX3 than controls and the synovial tissue contained endothelial cells and synoviocytes positive for PTX3 by immunohistochemistry. In conclusion, PTX3 may play a role in inflammatory circuits of RA, and its relevance as a marker of disease activity deserves further study.

[Nailfold capillary microscopy in patients with antiphospholipid syndrome]. / La capillaroscopia periungueale in pazienti con sindrome da immunità anti fosfolipidica.

In this paper we tried to define the capillaroscopic pattern of anti phospholipid syndrome able to differentiate between the primary (PAPS) and the systemic lupus erythematosus-associated form (SLE-APS) and to be a predictive marker of thrombotic manifestations. Eight PAPS and five SLE-APS patients were studied. In each patient the evaluation was based on anti cardiolipin antibody levels, nailfold capillaroscopy, retinal fluorangiography and transcranial doppler sonography. Statistical analysis has been performed using chi 2 analysis. Morphological alterations of capillary loops, venular visibility and sludging of blood were often observed in both groups. While we found in higher prevalence a variability of capillary loop length in PAPS patients, the SLE-APL group significantly differed for the presence of microhaemorrhages (p < 0.001). When we evaluated the clinical history, a marked microcirculatory damage was related with the occurrence of thrombotic manifestations in the PAPS patients. Anti cardiolipin antibody levels, retinal fluorangiography and transcranial doppler sonography did not correlate with clinical history in either group. In conclusion, nailfold capillaroscopy can be usefully employed in the differentiation between primary and SLE-associated anti phospholipid syndrome, and it can help to identify the patients at higher risk of thrombotic disease.

[Neuro-SLE. Models of its clinical expression]. / Neuro-LES. Modelli di espressione clinica.

In this paper we considered different models concerning the clinical expression of neuropsychiatric involvement in course of systemic lupus erythematosus (SLE). These models describe pathological conditions as multifocal cerebropathy, transverse myelitis, peripheral neuropathy and panic attacks. We have chosen these cases as clinical example of different pathogenic mechanisms responsible of CNS-lupus, as hypercoagulation due to antiphospholipid syndrome, immune-complex vasculitis, complement-mediated autoantibody damage and antibody-induced cytotoxicity. The prevalence of neuropsychiatric manifestations in 122 SLE patients is also reported. Finally, the paper reports some guidelines about diagnostic and therapeutic behaviour in course of CNS-lupus.

Terminal complement complex in synovial tissue from patients affected by rheumatoid arthritis, osteoarthritis and acute joint trauma.

The C5b-9 complex (Terminal Complement Complex-TCC) is the final product of the terminal complement pathway. In this study, using the monoclonal antibody MCaE11 (specific for a C9 neoantigen) and an immunohistochemical technique, we examined the TCC deposits in synovial tissues from 4 patients affected by rheumatoid arthritis (RA) and 6 patients affected by osteoarthritis (OA). Synovial tissues from 8 patients affected by acute joint trauma were examined as controls. Furthermore, plasma TCC levels were measured in 44 RA patients and 51 controls, using the above mentioned antibody and a sandwich ELISA. Eight synovial fluids were also included in this study. Abundant TCC deposits were detected in the cytoplasm of the synovial lining cells and of large stromal mononuclear cells in all the RA and in 3 out of 6 OA synovial tissues characterized by histological signs of inflammation. No TCC deposits were found in non-inflamed synovial tissues from patients with joint trauma. In agreement with previous observations, the TCC plasma levels found were significantly higher in RA patients than in controls, but no difference was seen between patients with active and non-active disease. The mean TCC level was significantly higher in the synovial fluid than in the plasma, but no correlation emerged between these two series of values. This study shows that: a) the plasma level of TCCs cannot serve as an indicator of disease activity in RA; b) the TCC deposits in synovial tissue correlate well with the extent of inflammatory synovitis, irrespective of whether the synovitis is rheumatoid or osteoarthritic in nature.

MR imaging of rheumatoid hand lesions: comparison with conventional radiology in 31 patients.

The purpose of this study was to evaluate the diagnostic accuracy of magnetic resonance imaging (MRI) in rheumatoid arthritis (RA) by comparing MRI with conventional radiology (CR) findings and by correlating these findings with the clinical and serological profile of the disease. The hands of 31 patients (24 females, 7 males) affected by classical RA were studied using a Magnetom 1.0 T tomograph. Coronal, axial, and/or sagittal SE T1 and GE (FLASH 2D FL: 70 degrees-15 degrees) images were obtained in all patients. Moreover, in 7 patients the MRI study was performed after i.v. injection of Gd DTPA contrast medium (0.2 mM/kg). Ten healthy volunteers were also studied as controls. In all patients a conventional radiological study was performed as well as a clinical and serological investigation. Two blinded observers evaluated the MRI and CR findings and checked 15 elementary pathological lesions, assigning an MRI and a CR score to each patient. MRI provided higher accuracy than CR in detecting rheumatoid soft tissue changes and minimal skeletal lesions, while the opposite was true for severe skeletal lesions. No correlations emerged between the MRI/CR findings and clinical and serological data. This study suggests that MRI and CR are complementary techniques in the evaluation of the anatomical changes in RA.

Low number of complement C3b/C4b receptors (CR1) on erythrocytes from patients with essential mixed cryoglobulinemia, systemic lupus erythematosus and rheumatoid arthritis: relationship with disease activity, anticardiolipin antibodies, complement activation and therapy.

Our aim was to assess whether the amount of complement C3b/C4b receptors (CR1) on erythrocytes shows a correlation to disease activity in various connective tissue diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and essential mixed cryoglobulinemia (EMC). Using an anti-CR1 monoclonal antibody, 26 patients with SLE, 34 with RA and 22 patients with EMC were investigated for erythrocyte CR1 expression. The control group consisted of 30 healthy individuals. The mean number of CR1/erythrocyte in the control group was 568 +/- 197 (range 174-1060), significantly higher than studied (EMC:379 +/- 248; p = 0.0005;SLE 147 +/- 56, p less than 0.0001; RA 298 +/- 177, p less than 0.0001). In patients with RA and in SLE, but not in patients with EMC, the number of CR1 numbers and anticardiolipin antibody (aCl) titers (r2 = 0.493; p = 0.034). A statistically significant correlation between CR1 numbers and CH50 values was found in patients with SLE, while in 3 patients with RA 4 months of therapy with cyclosporine A led to a further 30% reduction in CR1 number. Our conclusions are that (a) the decreased expression of erythrocyte CR1 is apparently a common feature of patients with various connective tissue diseases; (b) several acquired factors such as disease activity, complement activation, aCl and drugs may contribute to the loss of CR1 from erythrocytes; (c) in patients with RA and SLE, but not in patients with EMC, CR1 enumeration on erythrocytes may serve as a variable for clinical monitoring.

5-Methylcytosine content of DNA in blood, synovial mononuclear cells and synovial tissue from patients affected by autoimmune rheumatic diseases.

The percentage of 5-methylcytosine (m5Cyt) has been determined in peripheral blood, synovial mononuclear cells and synovial tissue from patients affected by various rheumatic autoimmune diseases. The determination was performed by reversed-phase high-performance liquid chromatography. Fifteen controls were compared to twenty-one patients affected by rheumatoid arthritis and to nine patients affected by systemic lupus erythematosus. The mean percentage of m5Cyt in normal individuals was significantly higher than in the rheumatoid arthritis and systemic lupus erythematosus patients. In addition, patients with active disease showed lower values than patients in remission. This finding is in agreement with the hypothesis that DNA hypomethylation may play a role in the pathogenesis of the autoimmune diseases, resulting in altered oncogene expression. Therapy with cyclosporin A led to a decrease in the percentage of m5Cyt in three rheumatoid arthritis patients, but a rebound was observed when the cyclosporin A was suspended. The percentage of m5Cyt in the DNA of synovial tissue from four rheumatoid arthritis patients and five patients with osteoarthritis was similar; this observation confirms that, in addition to disease-specific and disease activity-specific variations, the percentage of m5Cyt may also show tissue-specific variations.

Tenoxicam and ketoprofen level monitoring with high performance liquid chromatography in patients affected by rheumatoid arthritis.

A new reversed-phase high-performance liquid chromatography (HPLC) technique was employed in order to monitor the plasma Tenoxicam (TNX) levels in 13 patients affected by rheumatoid arthritis who were participating in a short-term, controlled, randomized, double-blind TNX (20 mg once a day) vs Ketoprofen (KPF) study. The HPLC method described by Sutterwhite was used to measure the KPF levels in plasma samples from 10 rheumatoid patients assigned to the treatment with this drug (100 mg twice a day). The mean (+/- 1 SD) steady-state plasma TNX concentration was 11.138 +/- 3.55 micrograms/ml. Twelve out of 13 patients had a drug level within the steady-state range and 8 out of these 12 patients showed clinical improvement. A synovial fluid TNX concentration slightly lower than plasma levels (11.04 vs 13.58 micrograms/ml), and TNX synovial tissue levels remarkably lower than plasma levels (1.02 vs 3.5 and 0.85 vs 4.1 micrograms/ml) were observed in three further rheumatoid patients. The mean plasma concentration of KPF (+/- 1 SD) was 3.23 +/- 2.68 micrograms/ml and only two patients showed drug levels within the therapeutic range. In some cases the lack of compliance with the treatment regimen was proved in both groups, and an explanation for the poor efficacy of the drug was provided. A positive clinical result was reached in some of the patients with low drug plasma levels, in both the TNX and KPF groups. Gastrointestinal side-effects were observed in 4 patients from both groups, 2 within the therapeutic range and 2 below. This finding confirms that several variables, in addition to the plasma drug concentration, condition the efficacy and side-effects of an NSAID.

Interleukin-2, soluble interleukin-2 receptor and tumor necrosis factor in sera from patients with rheumatoid arthritis.

Interleukin-2 (IL-2), soluble interleukin-2 receptor (IL-2R) and tumor necrosis factor (TNF) have been measured in sera from 47 patients affected by classic rheumatoid arthritis (RA) using an enzyme-linked immunosorbent assay. The patients were divided into 4 groups as follows: group A, 18 patients with inactive disease; group B, 19 patients with active disease under treatment with non-steroidal antiinflammatory drugs (NSAID) and second-line drugs; group C, 5 patients with active disease under treatment with NSAID and cyclosporine A (CSA) for at least 4 months; group D, 5 patients in the same condition as patients of group C, but treated with azathioprine (AZA) instead of CSA. IL-2 was undetectable in all patients except two, both characterized by active disease. Soluble IL-2R levels were above the upper limit of the normal range in most of the patients studied, but the mean value ( +/- 1 SD) was significantly higher in patients of group B (1,288 +/- 421 U/ml) than in patients of group A (686 +/- 205 U/ml) and group C (842 +/- 414 U/ml). In two patients affected by active RA treated with pulse methylprednisolone therapy (1 g/day for 3 alternate days) the values of soluble IL-2R dropped from 948 to 662 U/ml and from 660 to 518 U/ml, respectively. No statistically significant correlation was observed between the serum level of IL-2R and the RF titre or percentage of C1q-binding activity, respectively. TNF was found within the normal range in all patients except one, who was characterized by active arthritis, high number of rheumatoid skin nodules and extremely high RF titre.(ABSTRACT TRUNCATED AT 250 WORDS)