Retention rate of abatacept in rheumatoid arthritis patients in a real-life setting: results from a monocentric cohort.

OBJECTIVE: Data from trials demonstrated that abatacept (ABA) has a good safety and efficacy profile in treating rheumatoid arthritis. We have studied the retention rate of ABA in a real-life cohort of patients with rheumatoid arthritis. METHODS: This is a monocentric, retrospective study including patients with rheumatoid arthritis classified by the American College of Rheumatology/European League Against Rheumatism 2010 criteria who started treatment with ABA. The Kaplan-Meier method was applied to evaluate the ABA retention rate. RESULTS: This analysis was conducted on 161 patients [male/female 21/140, median age 65 years, interquartile range (IQR) 18.7, median disease duration 169 months, IQR 144.0]. 111 patients (68.9%) received ABA subcutaneously. ABA was associated with methotrexate in 61.9% of patients and was the first biological disease-modifying antirheumatic drug in 41%. We observed a median ABA survival of 66 months [95% confidence interval (CI) 57.3-74.7], with a retention rate of 88% at 6 months and 50.9% at 5 years. Drug survival was significantly higher in patients treated with ABA subcutaneously and in male patients (p=0.039 and p=0.018, respectively). Adjusted for main confounders, female gender was the main predictor of withdrawal (hazard ratio 5.1, 95% CI 1.2-21.3). CONCLUSIONS: Our study shows that better survival is associated with subcutaneous administration and male gender, confirming ABA effectiveness.

Anti-tumor necrosis factor α: originators versus biosimilars, comparison in clinical response assessment in a multicenter cohort of patients with inflammatory arthropathies.

OBJECTIVE: To compare etanercept and adalimumab biosimilars (SB4 and ABP501) and respective bioriginators in terms of safety and efficacy in a real-life contest. METHODS: We consequently enrolled patients affected by rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis, treated with SB4, and ABP501, or with corresponding originators, belonging to the main biological prescribing centers in the Lazio region (Italy), from 2017 to 2020. Data were collected at recruitment and after 4, 8, 12, and 24 months of therapy. RESULTS: The multicenter cohort was composed by 455 patients treated with biosimilars [SB4/ABP501 276/179; female/male 307/146; biologic disease-modifying anti-rheumatic drug (b-DMARD) naïve 56%, median age/ interquartile range 55/46-65 years] and 436 treated with originators (etanercept/adalimumab 186/259, female/ male 279/157, b-DMARD naïve 67,2%, median age/interquartile range 53/43-62 years). No differences were found about safety, but the biosimilar group presented more discontinuations due to inefficacy (p<0.001). Female gender, being a smoker, and being b-DMARD naïve were predictive factors of reduced drug survival (p=0.05, p=0.046, p=0.001 respectively). The retention rate at 24 months was 81.1% for bioriginators and 76.5% for biosimilars (median retention time of 20.7 and 18.9 months, respectively) (p=0.002). Patients with remission/low disease activity achievement at 4 months showed a cumulative survival of 90% to biosimilar therapy until 24 months (p=0.001); early adverse reactions instead represented a cause of subsequent drug discontinuation (p=0.001). CONCLUSIONS: Real-life data demonstrated a similar safety profile between biosimilars and originators, but a reduced biosimilar retention rate at 24 months. Biosimilars could be considered a valid, safe, and less expensive alternative to originators, allowing access to treatments for a wider patient population.

Porphyromonas gingivalis in the tongue biofilm is associated with clinical outcome in rheumatoid arthritis patients.

Several studies have suggested a link between human microbiome and rheumatoid arthritis (RA) development. Porphyromonas gingivalis seems involved in RA initiation and progression, as supported by the high occurrence of periodontitis. In this case-control study, we analysed tongue P. gingivalis presence and quantification in a large healthy and RA cohort. We enrolled 143 RA patients [male/female (M/F) 32/111, mean ± standard deviation (s.d.), age 57·5 ± 19·8 years, mean ± s.d. disease duration 155·9 ± 114·7 months); 36 periodontitis patients (M/F 11/25, mean ± s.d., age 56 ± 9·9 years, mean ± s.d. disease duration 25·5 ± 20·9 months); and 57 patients (M/F 12/45, mean ± s.d., age 61·4 ± 10·9 years, mean ± s.d. disease duration 62·3 ± 66·9 months) with knee osteoarthritis or fibromyalgia. All subjects underwent a standard cytological swab to identify the rate of P. gingivalis/total bacteria by using quantitative real-time polymerase chain reaction. The prevalence of P. gingivalis resulted similarly in RA and periodontitis patients (48·9 versus 52·7%, P = not significant). Moreover, the prevalence of this pathogen was significantly higher in RA and periodontitis patients in comparison with control subjects (P = 0·01 and P = 0·003, respectively). We found a significant correlation between P. gingivalis rate in total bacteria genomes and disease activity score in 28 joints (DAS28) (erythrocyte sedimentation rate) (r = 0·4, P = 0·01). RA patients in remission showed a significantly lower prevalence of P. gingivalis in comparison with non-remission (P = 0·02). We demonstrated a significant association between the percentage of P. gingivalis on the total tongue biofilm and RA disease activity (DAS28), suggesting that the oral cavity microbiological status could play a role in the pathogenic mechanisms of inflammation, leading to more active disease.

Distribution of interleukin-10 family cytokines in serum and synovial fluid of patients with inflammatory arthritis reveals different contribution to systemic and joint inflammation.

Evidence exists that interleukin (IL)-10 family cytokines may be involved in the pathogenesis of rheumatoid arthritis (RA). We sought to determine whether or not these cytokines are involved in psoriatic arthritis (PsA). We conducted a prospective study on patients with PsA, RA and osteoarthritis (OA); healthy controls (HC) were also included. We analysed IL-20, IL-24 and IL-19 serum and synovial fluid (SF) levels and change of serum levels following treatment with biological agents. IL-20 serum levels were increased in PsA and RA compared with OA patients and HC and with matched SF levels. IL-24 serum levels in PsA, RA and OA patients were higher than those in HC and also with respect to matched SF in PsA. IL-19 serum levels were higher in HC and OA compared with PsA and RA patients; IL-19 SF levels were higher in PsA and RA compared with OA patients, and in PsA compared with RA patients. PsA and RA patients showed a reduction of IL-19 serum levels after biological treatment. Therefore, IL-19 seems to be involved mainly in the joint inflammation, whereas IL-20 and IL-24 appear to participate mainly in the systemic responses. These findings may further the comprehension of the contribution of these cytokines to the inflammatory response involved in chronic arthritis, as well as to the development of novel therapeutic strategies.

Anti-carbamylated protein antibodies in unaffected first-degree relatives of rheumatoid arthritis patients: lack of correlation with anti-cyclic citrullinated protein antibodies and rheumatoid factor.

OBJECTIVES: To investigate the prevalence of anti-carbamylated protein antibodies (anti-CarP) in the healthy first-degree relatives (HFDRs) of patients with rheumatoid arthritis (RA). METHODS: We enrolled 141 HFDRs of 63 patients with RA diagnosed accordingly to the 2010 ACR/EULAR criteria. Fifty-six normal healthy subjects (NHS), sex- and age-matched, served as controls. Anti-CarP IgG, anti-cyclic citrullinated peptide antibody (anti-CCP) IgG and rheumatoid factors (RF) isotypes (IgG, IgA, IgM) were assessed by solid-phase ELISA. RESULTS: Anti-CarP were detectable in 13 HFDRs (9.2%), anti-CCP in 9 (6.3%), IgG-RF in 10 (7%), IgA-RF in 17 (12%), and IgM-RF in 13 (9.2%) HFDRs. Twenty-nine (46%) RA patients were positive for anti-CarP, 31 (49.2%) for anti-CCP, and 34 (53.9%) for RF. One NHS (1.7%) resulted positive for anti-CarP, none for anti-CCP and RF. Anti-CarP showed significantly higher serum levels in RA and HFDRs than in NHS (p<0.0001 and p=0.0012, respectively). A significant correlation between anti-CCP and RF were found among RA patients (p=0.0002), whereas no correlations were reported between autoantibodies tested in the HFDRs. CONCLUSIONS: Anti-CarP can be found in the sera of HFDRs of RA patients and their prevalence is significantly higher than in NHS. No correlation of anti-CarP with anti-CCP and RF antibodies in RA HFDRs was found.

Pain in rheumatoid arthritis: a critical review.

Patients with rheumatoid arthritis (RA) are frequently afflicted by pain, which may be caused by joint inflammation (leading to structural joint damage) or secondary osteoarthritis, and may be increased by central sensitisation. Non-inflammatory pain may also confuse the assessment of disease activity, and so the aim of treatment is not only to combat inflammatory disease, but also relieve painful symptoms. In order to ensure effective treatment stratification, it is necessary to record a patients medical history in detail, perform a physical examination, and objectively assess synovitis and joint damage. The management of pain requires various approaches that include pharmacological analgesia and biological and non-biological treatments. Although joint replacement surgery can significantly improve RA-related pain, it may only be available to patients with the most severe advanced disease.

Chronic widespread pain in spondyloarthritis.

The pain associated with spondyloarthritis (SpA) can be intense, persistent and disabling. It frequently has a multifactorial, simultaneously central and peripheral origin, and may be due to currently active inflammation, or joint damage and tissue destruction arising from a previous inflammatory condition. Inflammatory pain symptoms can be reduced by non-steroidal anti-inflammatory drugs, but many patients continue to experience moderate pain due to alterations in the mechanisms that regulate central pain, as in the case of the chronic widespread pain (CWP) that characterises fibromyalgia (FM). The importance of distinguishing SpA and FM is underlined by the fact that SpA is currently treated with costly drugs such as tumour necrosis factor (TNF) inhibitors, and direct costs are higher in patients with concomitant CWP or FM than in those with FM or SpA alone. Optimal treatment needs to take into account symptoms such as fatigue, mood, sleep, and the overall quality of life, and is based on the use of tricyclic antidepressants or selective serotonin reuptake inhibitors such as fluoxetine, rather than adjustments in the dose of anti-TNF agents or disease-modifying drugs.

Pain and systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by heterogeneous clinical manifestations involving virtually the entire body. The pain in SLE can have different causes. The SLE classification criteria include mainly the musculoskeletal manifestations of pain, which are commonly reported as initial symptoms of SLE, such as arthralgia, arthritis and/or myalgia. Chronic widespread pain, which is typical of fibromyalgia (FM), is frequently associated with SLE. The aim of this review is to describe widespread pain and fatigue in SLE, and the association of SLE and FM. Although secondary FM is not correlated with the disease activity, it may interfere with the daily activities of SLE patients. Therefore it is necessary to identify its symptoms and treat them promptly to improve the quality of life of patients. In conclusion, it is essential to identify the origin of pain in SLE in order to avoid dangerous over-treatment in patients with co-existing widespread pain and FM.

Role of micronutrients in the symptoms of fibromyalgia: a review of the literature and analysis of an Italian female sample.

OBJECTIVE: Fibromyalgia (FM) is a multifactorial disease characterized principally by chronic, widespread pain impairing a patient's quality of life. The management of FM requires a multidisciplinary approach that combines pharmacological and non-pharmacological strategies. Growing evidence suggests a potential beneficial role of micronutrients such as minerals and vitamins. Overall, the role of these supplements remains controversial, but clinical trials on vitamin D, vitamin B12, magnesium, and iron supplementation seem to provide promising results. The aim of this study was to investigate their role in an Italian female sample. SUBJECTS AND METHODS: An exploratory cross-sectional study was done to assess the association of selected micronutrients with symptoms of FM by using the Fibromyalgia Impact Questionnaire (FIQ) in twenty consecutive female patients with FM. A literature review was also conducted. RESULTS: FIQ results revealed that vitamin D and magnesium deficiency appear to play a role in FM symptoms, mainly in physical function and stiffness. From the literature review, only two studies investigating the role of micronutrients in FM were retrieved. CONCLUSIONS: Screening for micronutrient deficiencies in FM patients and supplementing them when levels are low might help counteract FM symptoms.

Effect of therapeutic inhibition of TNF on circulating endothelial progenitor cells in patients with rheumatoid arthritis.

Endothelial dysfunction has been detected in RA patients and seems to be reversed by control of inflammation. Low circulating endothelial progenitor cells (EPCs) have been described in many conditions associated with increased cardiovascular risk, including RA. The aim of this study was to investigate the effect of inhibition of TNF on EPCs in RA patients. Seventeen patients with moderate-severe RA and 12 sex and age-matched controls were evaluated. Endothelial biomarkers were tested at baseline and after 3 months. EPCs were identified from peripheral blood mononuclear cells by cytofluorimetry using anti-CD34 and anti-vascular endothelial growth factor-receptor 2. Asymmetric dimethylarginine (ADMA) was tested by ELISA and flow-mediated dilatation (FMD) by ultrasonography. Circulating EPCs were significantly lower in RA patients than in controls (P = 0.001). After 3 months EPCs increased significantly (P = 0.0006) while ADMA levels significantly decreased (P = 0.001). An inverse correlation between mean increase in EPCs number and mean decrease of DAS28 after treatment was observed (r = -0.56, P = 0.04). EPCs inversely correlated with ADMA (r = -0.41, P = 0.022). No improvement of FMD was detected. Short-term treatment with anti-TNF was able to increase circulating EPCs concurrently with a proportional decrease of disease activity suggesting that therapeutic intervention aimed at suppressing the inflammatory process might positively affect the endothelial function.

Fibromyalgia and arthritides.

Fibromyalgia (FM) is a chronic pain syndrome that affects at least 2% of the adult population. It is characterised by widespread pain, fatigue, sleep alterations and distress, and emerging evidence suggests a central nervous system (CNS) malfunction that increases pain transmission and perception. FM is often associated with other diseases that act as confounding and aggravating factors, such as rheumatoid arthritis (RA), spondyloarthritides (SpA), osteoarthritis (OA) and thyroid disease. Mechanism-based FM management should consider both peripheral and central pain, including effects due to cerebral input and that come from the descending inhibitory pathways. Rheumatologists should be able to distinguish primary and secondary FM, and need new guidelines and instruments to avoid making mistakes, bearing in mind that the diffuse pain of arthritides compromises the patients' quality of life.

Preliminary identification of key clinical domains for outcome evaluation in fibromyalgia using the Delphi method: the Italian experience.

OBJECTIVE: Fibromyalgia (FM) is a complex syndrome that, in Italy, affects at least 2% of the adult population. It is characterized by chronic widespread musculoskeletal pain often accompanied by multiple other symptoms. The aim of this study was to identify a set of clinical domains for FM considered relevant by both clinicians and patients using a consensus process. METHODS: Consensus was achieved using the Delphi method based on questionnaires and systematic, controlled opinion feedback. The Delphi exercise involved a panel of 252 rheumatologists and 86 patients with FM as defined by the American College of Rheumatology criteria. All of the patients and clinicians were asked to rank the relative different domains of FM in order of priority. The content validity index (CVI) was used to establish the percentage agreement. The importance of each item was ranked on a 0-3 Likert scale. The frequency, mean relevance scores, and frequency importance product were also calculated. RESULTS: The Delphi exercise showed that the domains ranked highest by patients were similar to those of the clinicians, with the exception of tender point intensity (considered relevant by the clinicians but not by the patients) and environmental sensitivity (considered important by the patients but not by the clinicians). A final 8-item model was developed which was considered to demonstrate adequate validity. CONCLUSIONS: The Delphi exercises identified and ranked relevant key clinical domains that need to be assessed in FM research. On the basis of these results, a new patient-reported composite outcome index can be developed and used in clinical trials.

Misdiagnosis in fibromyalgia: a multicentre study.

BACKGROUND: Fibromyalgia (FM) is the second most common cause of visits to rheumatologists after osteoarthritis, and may be difficult to diagnose in many patients. It is associated with various rheumatic disorders such as rheumatoid arthritis, spondyloarthropathies (SpA) and connective tissue disease (CTD), and a late diagnosis or misdiagnosis is a common and underestimated problem. OBJECTIVES: The aim of this study was to investigate the 'underdiagnosis' of FM, and which rheumatic diseases tend to be confused with it. METHODS: The following data were collected at baseline: symptoms, disease duration, physical examination findings, previous and current investigations and management, laboratory tests, tender point count, tender and swollen joint counts, and spinal pain. The clinimetric evaluation included the Fibromyalgia Impact Questionnaire (FIQ) and Fibromyalgia Assessment Status (FAS). RESULTS: The study population consisted of 427 outpatients (418 females and 9 males; mean age 49.3 years; mean disease duration 8.5 years). Fifty-seven patients (13.3%) had been previously misdiagnosed as having other musculoskeletal disorders (MSDs); 370 patients had been previous correctly diagnosed as having FM, or were diagnosed as having it during the course of the study. The FM and MSD groups were comparable in terms of demographic data and referral patterns. Disease duration was longer and the erythrocyte sedimentation rate was higher in the MSD patients, who also had less severe FIQ and lower pain visual analogue scale scores. Moreover, the FIQ and FAS scores correlated in the MS group. CONCLUSIONS: The findings of this study suggest that, although FM is a wellknown clinical entity, differential diagnosis with SpA, CTD and inflammatory arthritis can still be a challenge for rheumatologists and general practitioners.

Psychometric properties of the Fibromyalgia Assessment Status (FAS) index: a national web-based study of fibromyalgia.

Fibromyalgia (FM) is a generalized chronic pain condition that is often accompanied by symptoms such as fatigue, sleep disturbances, psychological and cognitive alterations, headache, migraine, variable bowel habits, diffuse abdominal pain, and urinary frequency. Its key assessment domains include pain, fatigue, disturbed sleep, physical and emotional functioning, and patient global satisfaction and health-related quality of life (HRQL). A number of evaluation measures have been adapted from the fields of rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis, and others such as the Fibromyalgia Assessment Status (FAS) index and the Fibromyalgia Impact Questionnaire (FIQ) have been specifically developed. The aim of this study was to assess the impact of FM on HRQL by comparing the performance of the FAS index, the FIQ and the Health Assessment Questionnaire [HAQ] in 541 female and 31 male FM patients (mean age 50 years; mean disease duration 7.7 years) entered in the database of a web-based survey registry developed by the Italian Fibromyalgia Network (IFINET). Tests of convergent validity showed that the FAS index and FIQ significantly correlated with each other (rho=0.608, p<0.0001), but there were also significant correlations between the FAS index and other clinical measures of disability, including the HAQ (rho=0.423, p<0.0001), anxiety (rho=0.138, p=0.0009), depression (rho=0.174, p<0.0001) and, especially, the number of comorbidities (rho=0.147, p=0.0004). The FAS index revealed a statistically significant difference between males and females (p=0.048), analysed using the Mann-Whitney U-test for all pair wise comparisons. The FAS index is a valid three-item instrument (pain, fatigue and sleep disturbances) that performs at least as well as the FIQ in FM patients, and is simpler to administer and score. Both questionnaires may be useful when screening FM patients, with the choice of the most appropriate instrument depending on the setting.

Domestic violence detection amid the COVID-19 pandemic: the value of the WHO questionnaire in emergency medicine.

BACKGROUND: Gender-based violence affects 35-45% of women worldwide, mostly coming from domestic violence. A good screening procedure in clinical practice is useful, but WHO does not advise universal screening, recommending further research. AIM: (i) To report the frequency of domestic violence cases among admissions to the Emergency Room of a major Italian Hospital in 2020, including during complete 'Lockdown' period; (ii) to document acute and chronic health effects of domestic violence and (iii) to asses usefulness of the WHO screening as a tool for uncovering cases which would otherwise remain hidden. DESIGN AND METHODS: A database containing all the information recorded for each of 19 160 patients in the Emergency Room was constructed by a keyword search ('violence', 'assault', 'trauma') to filter the data and retrieve cases of violence in the period between 1 January and 2 June 2020. The self-administered questionnaire of the WHO Multi-country Study on Women's Health and Domestic Violence against Women was used in women referred to the emergency room for any cause, excluding trauma. RESULTS: A recent history of domestic violence was disclosed by 22.67%, after completing the WHO questionnaire. Of those not participating in the survey, diagnosis of domestic violence was only 0.6% (128/19 160). CONCLUSION: Power of detection of domestic violence by the WHO questionnaire is very high, while the frequency of occurrence of these events in this population was considerable. Seemingly, it elicits the responsiveness to the topic of the volunteer interviewees. Its use should be firmly recommended, reasonably, while Covid-19 pandemic is affecting health, rights and response.

Exploratory data analysis on the effects of non pharmacological treatment for knee osteoarthritis.

OBJECTIVES: Osteoarthritis (OA) is a chronic rheumatic disease characterized by progressive cartilage destruction mediated by cytokines and other molecules. Chondrocyte activity and metabolism have attracted interest as targets of drug intervention, and spa-therapy can influence the serum levels of several cytokines. We investigated the effects of spa-therapy on clinical and ultrasonographic (US) findings and serum levels of cartilage oligomeric matrix protein (COMP) and several cytokines, chemokines, and growth factors in a prospective cohort of patients with symptomatic knee OA. METHODS: Patients (n=53) with primary symptomatic knee OA were treated for 12 consecutive days with locally applied mud-packs. Assessments were made at baseline, immediately after completion of the treatment cycle, and 6 and 12 months after completion of treatment. They included visual analogue scale (VAS) ratings of pain, the Lequesne algofunctional index for knee OA, and US with calculation of a semiquantitative score that expressed the severity of the local inflammatory process. Serum levels of 27 cytokines (including interferon--inducible protein-10 [IP-10]), chemokines, and growth factors were measured with multiplex bead-based immunoassays, and COMP levels were determined by ELISA. RESULTS: US scores, VAS pain ratings, and Lequesne indexes indicated significant improvement after spa-therapy and at the 6- and 12-month follow-ups. Serum IP-10 levels also dropped significantly (p=0.0035), and this reduction was positively correlated with improvement of the Lequesne index (p=0.031). CONCLUSIONS: In patients with knee OA, spa-therapy can modulate serum levels of proinflammatory cytokines/chemokines and produce improvements in joint pain and function that persists for up to 1 year.

Fatigue in Sjogren's syndrome: relationship with fibromyalgia, clinical and biologic features.

More than two third of patients with primary Sjögren's syndrome (SS) report fatigue. Despite its clinical relevance, only a few studies have examined the relationship of fatigue with the presence of an overlapping Fibromyalgia (FM) and other clinical and biological variables. The aim of this study was to assess the relationship between fatigue and SS disease activity and damage, FM, widespread pain, and mood disorders; finally, the possible correlation between fatigue and a panel of cytokines likely to drive the immunopathological process of the disease has been examined. Thirty-five female patients with primary SS were consecutively enrolled; for each patient the Sjögren's Syndrome Disease Damage Index (SSDDI) and the Sjögren's Syndrome Disease Activity Index (SSDAI) were calculated. Patients rated pain, fatigue and disease activity using a 100-mm VAS and completed Health Assessment Questionnaire (HAQ), the Zung depression (ZSDS) and anxiety scales (ZSAS). 30/35 patients (85.7%) felt unduly tired and the same percentage of patients suffered with pain in more than one area of the body. 7 patients satisfied ACR criteria for FM, representing 20% of the whole cohort and 23% of SS patients with fatigue. No differences were found in disease duration, SSDDI, SSDAI, ZSDS and ZSAS among SS patient with or without FM. In the whole group, fatigue VAS correlated with HAQ, ZSAS, ZSDS and pain VAS but not with age, disease duration, presence and severity of arthritis, SSDDI, SSDAI, or cytokines. In conclusion, an overlapping FM can contribute to, but does not entirely account for fatigue in Italian patients with primary SS.

Pharmacological treatment of fibromyalgia.

Fibromyalgia (FM) is a common syndrome characterised by widespread pain and at least 11/18 painful tender points that requires multimodal pharmacological treatment also combined with non-pharmacological therapy. Various drugs currently are available to control the complex and different symptoms reported by patients. Only three drugs (duloxetine, milnacipram, pregabalin) are approved by the American Food and Drug Administration (FDA) and none by the European Medicines Agency (EMEA), consequently, off-label use is habitual in Europe. Most of the drugs improve only one or two symptoms; no drug capable of overall symptom control is yet available. Furthermore, different classes of drugs with different mechanisms of action are used off-label, including tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), opioids, non-steroidal anti-inflammatory drugs (NSAIDs), growth hormone, corticosteroids and sedative hypnotics. As no single drug fully manages FM symptoms, multicomponent therapy should be used from the beginning. Various pharmacological treatments have been used to treat FM with inconclusive results, and gradually increasing low doses is suggested in order to maximise efficacy. The best treatment should be individualised and combined with patient education and non-pharmacological therapy.

Computed tomography and thymoma: distinctive findings in invasive and noninvasive thymoma and predictive features of recurrence.

PURPOSE: Our goal was to assess the computed tomography (CT) imaging findings of thymoma and to correlate these features with Masaoka staging system and prognosis. MATERIALS AND METHODS: CT findings of thymoma were analysed in 58 patients who had undergone surgery between January 2002 and September 2007. All cases were classified according to the Masaoka staging system. The presence of various CT findings was correlated with tumour invasiveness and recurrence. In statistical analysis, a p value <0.05 was interpreted as significant. RESULTS: The study found 26 noninvasive thymomas and 32 invasive thymomas. Invasive thymomas were more likely to be greater in size (p<0.01), with lobulated or irregular contours (p<0.02), a necrotic or cystic component (p<0.04), foci of calcification (p<0.05) and heterogeneous contrast enhancement (p<0.01) than were noninvasive thymomas. Disease progression developed in nine of 58 patients. Tumour recurrence and metastasis correlated with greater size (p<0.04), lobulated or irregular contours (p<0.01), complete mediastinal fat obliteration (p<0.01), great vessel invasion (p<0.01) and pleural implants (p<0.02). CONCLUSIONS: CT is useful in differentiating invasive from noninvasive thymomas and plays an important role in evaluating and treating these patients for multimodal therapy with neoadjuvant approaches. Moreover, CT findings may serve as predictors of postoperative recurrence or metastasis.

Autonomic dysfunction and neuropeptide Y in fibromyalgia.

OBJECTIVES: Fibromyalgia (FM) is a syndrome associated with widespread pain and various other signs and symptoms. Several of these multisystem features could be explained on the basis of autonomic nervous system (ANS) dysfunction. METHODS: The aim of the present study was to evaluate ANS dysfunction in FM based on time-domain heart rate variability (HRV) analysis and serum neuropeptide Y (NPY) levels in 51 patients with FM, 25 patients with systemic sclerosis (SSc), and 15 healthy controls (NHS). RESULTS: Compared with the SSc and NHS groups, the FM group had significantly higher NPY levels, and in the FM subgroup subjected to HRV analysis (25/51 patients, 49%), certain HRV indices were significantly reduced. In this subgroup, NPY was significantly correlated with the SDANN index and the NN50, but neither NPY or HRV parameters showed any significant correlation with clinical aspects of the FM. CONCLUSION: These findings suggest that autonomic dysfunction and NPY are crucial elements in the pathophysiology of FM. Additional studies are necessary to define the complex roles played by NPY and ANS in modulating pain and immunological functions of different diseases.