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Introduction: Psoriatic arthritis (PsA) is a chronic, progressive inflammatory joint disease that is associated with higher prevalence of depression. There is limited literature about the impact of depression, particularly regarding the response to therapy., Methods: A retrospective cohort study with PsA patients that started their first biologic disease-modifying antirheumatic drugs (bDMARD) was conducted. In the majority of cases, a cutoff score of ≥ 8 in Hospital Anxiety and Depression Scale (HADS) was used to define cases of depression. In cases where patients did not complete the questionnaire, a previous diagnosis made by a psychiatrist was used to establish the presence of depression. Response to therapy 12 months after the start of bDMARD was evaluated and the switch rate to another bDMARD due to inefficacy was assessed at month 12., Results: A total of 129 patients (66 females, 51.2%; mean age of 47.7 ± 11.0 years and mean disease duration of 10.0 ± 7.7 years) with PsA were included. Thirty-two (24.8%) patients had depression. Patients with depression and peripheral involvement had a significantly lower ACR20/50/70 responses (p = 0.001, p = 0.002, and p = 0.001 respectively) after 12 months of therapy and a significantly worse EULAR response (p = 0.002). Furthermore, patients with depression and axial involvement had a significantly worse response based on ASDAS response criteria (p = 0.031). Switch due to ineffectiveness in the first 12 months was significantly higher in patients with depression (p = 0.002)., Conclusion: Depression in PsA is a frequent yet often understudied comorbidity. The causal relationship between depression and PsA is difficult to decrypt and further research is needed. Recognition of depressive symptoms is crucial and a multidisciplinary approach should be provided to individuals with this comorbidity. Key Points • Depression in PsA is a frequent yet often understudied comorbidity. In our study, the prevalence of depression was 24.8%. • Depression in PsA seems to be associated to lower response to therapy and higher discontinuation rates of bDMARD. • Recognition of depressive symptoms is crucial and a multidisciplinary approach should be provided to individuals with this comorbidity., (© 2023. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Introduction and Hypothesis: Urinary incontinence (UI) affects approximately 50% of adult women worldwide and is associated with declining sexual function (SF). Energy-based devices emerged as a minimally invasive alternative treatment. Nevertheless, their effect on sexuality is uncertain. We hypothesize that the UI energy treatment can lead to sexual function improvement., Methods: A search was performed in PubMed, Cochrane Library, Web of Science, Embase, and Scopus for randomized clinical trials (RCTs) and nonrandomized studies of intervention, which treated incontinent women using energy, with UI and sexual function (SF) as outcomes. Severe comorbidities, pelvic organ prolapse (POP)> grade 2, and use of medication to treat UI or that affects SF were excluded. Quality assessment and meta-analysis were performed., Results: From 322 articles, 11 RCTs were included for qualitative analysis. UI symptoms improved in all studies. Regarding SF, RCT with premenopausal women showed improvement in SF in the Er:Yag group (Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire-12 and Female Sexual Function Index). A prospective study showed improvement in SF independent of the grade of SUI. RF showed benefits for SF but was not superior to pelvic floor muscle training. One nonrandomized study of intervention with a High-Intensity Focused Electromagnetic Field showed significant improvement of SF in the Golombok Rust Inventory of Sexual Satisfaction total score, a decline in pain and dissatisfaction domains. Meta-analysis with 4 RCTs and 2 nonrandomized studies found no difference between groups (0.26 (95% CI -0.67 to 1.20, and -0.74 (95% CI -3.78 to 2.30) respectively)., Conclusions: This meta-analysis did not confirm that energy equipment improved the SF of women with UI., (© 2023. The International Urogynecological Association.)

The inflammasomes are a family of recently described multi-protein cytoplasmic sensors that orchestrate the inflammatory response and participate in a variety of inflammatory conditions. We hypothesized that the activation of pyrin domain‑containing protein 3 (NLRP3) inflammasome by granulosa cells (hGCs) may be activated in women with endometriosis and influence oocyte maturation and IVF outcomes. We performed a cross-sectional study to investigate the NLRP3 inflammasome status in follicular fluid (FF) and in hGCs from 44 women undergoing controlled ovarian stimulation for IVF/ICSI. Study subjects were divided into two groups according to the infertility etiology: group with tubal or male factor (control, n = 22) vs. group with endometriosis (n = 22). The FF IL-1beta and IL-18 levels in the endometriosis group were significantly higher than those in the non-endometriosis group, i.e., 5010 pg/mL and 2738 pg/mL, respectively (p < 0.05). No correlation was found between clinical pregnancy and live birth rate and analyzed inflammasome component levels (p > 0.05). In addition, the hGCs from endometriosis women demonstrated high expression of NLRP3 inflammasome at both protein and mRNA levels. Higher expression of inflammasome components within the ovary compartment may result from the exaggerated inflammatory state associated with endometriosis and thus impact the fertility of these women., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Neuromyelitis optica spectrum disorder (NMOSD) is associated with a reduced health-related quality of life (HRQoL). The purpose of this study was to describe the impact of NMOSD on HRQoL from the patients' perspective and its relationship with other disease factors., Methods: An observational, cross-sectional study was conducted at 13 neuroimmunology clinics in Spain. Patients with NMOSD diagnosis (2015 Wingerchuk criteria) were included. The 29-item Multiple Sclerosis Impact Scale (MSIS-29) was used to assess the HRQoL. Different questionnaires were used to measure symptom severity, stigma, mood disorders, pain, fatigue, and difficulties in the workplace. Factors that impact HRQoL were identified by Spearman's correlation and multivariate linear regression analysis., Results: Seventy-one patients were included (mean age 47.4 ± 14.9 years, 80.3% female, mean time since disease onset 9.9 ± 8.1 years). The median Expanded Disability Status Scale score was 3.0 (1.5-4.5). The mean (± SD) physical and psychological MSIS-29 sub-scores were 41.9 ± 16.8 and 20.9 ± 8.3, respectively. Fatigue and body pain were the most prevalent symptoms. Depressive symptoms were found in 44.3% (n = 31) of patients. The physical MSIS-29 dimension showed the highest correlation with symptom severity (ρ = 0.85584, p < 0.0001), whereas the highest correlations for psychological MSIS-29 dimension were pain, MSIS-29 physical dimension, and depression (ρ = 0.76487, 0.72779, 0.71380; p < 0.0001, respectively). Pain was a predictor of both dimensions of MSIS-29., Conclusion: Fatigue, pain, and depressive symptoms are frequent problems among patients with NMOSD, impacting on their quality of life. Assessment of patient-oriented outcomes may be useful to achieve a holistic approach, allowing early specific interventions., (© 2022. The Author(s).)

The objective of this study is to describe the possible prognostic impact of smoking habit on adult-onset Still's disease (AOSD) patients, by the assessment of clinical characteristics, life-threatening complications occurrence, and mortality in smokers than non-smokers. A multicentre retrospective study of prospectively followed-up AOSD patients included in Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale (GIRRCS) cohort was conducted. Out of 185 AOSD assessed patients, 45 smokers were identified. These showed a higher frequency of pericarditis (35.5% vs 16.4%, p = 0.011), pleuritis (33.3% vs 14.3%, p = 0.008), and abdominal pain (17.7% vs 6.4%, p = 0.035). Furthermore, smokers showed higher values of systemic score (6.4 ± 2.2 vs 5.4 ± 1.8, p = 0.004), an increased rate of macrophage activation syndrome (MAS) (28.9% vs 6.4%, p < 0.0001) and of parenchymal lung disease (17.7% vs 12.6%, p = 0.035). Although not significant, these patients more frequently experienced a poor prognosis (13.3% vs 4.3%, p = 0.074). Smoking habit predicted MAS occurrence in both univariate (HR: 5.98, 95% CI: 2.45-14.57, p < 0.0001) and multivariate regression models (HR: 6.21, 95% CI: 2.46-15.70, p < 0.0001). Smokers had a significant higher risk of parenchymal lung disease in both univariate (HR: 3.97, 95% CI: 1.43-11.02, p = 0.008) and multivariate regression models (HR: 3.90, 95% CI: 1.36-11.23, p = 0.012). Smoking habit also increased the risk of mortality in univariate regression model (HR: 4.25, 95% CI: 1.33-13.55, p = 0.015). Smoking habit resulted to be a negative prognostic factor on AOSD patients. Smokers were characterised by a higher frequency of serositis and higher values of systemic score. Additionally, these patients were more frequently burdened by MAS and parenchymal lung disease associated with a poor prognosis. Key points • Smoking habit resulted to be a negative prognostic factor on AOSD. • Smokers were characterised by an increased frequency of serositis and higher values of systemic score. • Cigarette exposure was associated with MAS and parenchymal lung disease in AOSD., (© 2021. International League of Associations for Rheumatology (ILAR).)

Objectives: To determine the effectiveness of golimumab (GLM) in improving joint, periarticular structures and cutaneous manifestations in patients with moderate to severe psoriatic arthritis (PsA) with cutaneous psoriasis in different real-life clinical settings and 48-month drug survival., Methods: Clinical and laboratory records were collected from PsA patients treated with GLM at baseline (T0) and after 6, 12, 24, 36, and 48 months of treatment. Comparisons were performed using a paired t-test or Wilcoxon test. Drug survival rates were analyzed using Kaplan-Meier estimates. p value < 0.05 was considered statistically significant., Results: Data from 105 patients were collected. PsO occurred in 80% of patients and enthesitis in 78%, peripheral and axial arthritis in 63.8% and 35.3%, respectively, while erosions in 36.2%. The main comorbidities were cardiovascular diseases (31.4%) and metabolic syndrome (MetS) (19%). A statistically significant improvement in articular and cutaneous psoriasis was registered at T48 of GLM-therapy in clinical (DAPSA p < 0.0001; PASI p < 0.01; BASDAI p < 0.0001) and laboratory (CRP < 0.05) indexes. Gender (p = 0.652), BMI (p = 0.655), smoking habit (p = 0.466), and line of treatment (p = 0.208) did not affect treatment efficacy nor persistence. At T48, 42% of patients discontinued GLM: the most frequent reason was an insufficient response or loss of efficacy (28.6%)., Conclusion: A 48-month GLM high drug persistence of PsA patients was observed in real-life, in patients presenting high disease activity, elevated prevalence of comorbidities, and more than one line of treatment at baseline. Patients' characteristics as gender, smoke, BMI, different lines of treatment, and concomitant methotrexate treatment affected treatment persistence, making GLM effective and safe in moderate-severe PsA in a long-term real-life setting. Key Points • Golimumab was effective in psoriatic arthritis, including both musculoskeletal and cutaneous manifestations. • Golimumab effectiveness and drug survival were not affected by comorbidities and patient-related characteristics. • The 4-year drug survival curves confirm the efficacy and safety of golimumab in psoriatic arthritis patients in a real-life setting., (© 2021. The Author(s).)

Despite the increasing evidence of the benefit of corticosteroids for the treatment of moderate-severe coronavirus disease 2019 (COVID-19) patients, no data are available about the potential role of high doses of steroids for these patients. We evaluated the mortality, the risk of need for mechanical ventilation (MV), or death and the risk of developing a severe acute respiratory distress syndrome (ARDS) between high (HD) and standard doses (SD) among patients with a severe COVID-19. All consecutive confirmed COVID-19 patients admitted to a single center were selected, including those treated with steroids and an ARDS. Patients were allocated to the HD (≥ 250 mg/day of methylprednisolone) of corticosteroids or the SD (≤ 1.5 mg/kg/day of methylprednisolone) at discretion of treating physician. Five hundred seventy-three patients were included: 428 (74.7%) men, with a median (IQR) age of 64 (54-73) years. In the HD group, a worse baseline respiratory situation was observed and male gender, older age, and comorbidities were significantly more common. After adjusting by baseline characteristics, HDs were associated with a higher mortality than SD (adjusted OR 2.46, 95% CI 1.59-3.81, p < 0.001) and with an increased risk of needing MV or death (adjusted OR 2.35, p = 0.001). Conversely, the risk of developing a severe ARDS was similar between groups. Interaction analysis showed that HD increased mortality exclusively in elderly patients. Our real-world experience advises against exceeding 1-1.5 mg/kg/day of corticosteroids for severe COVID-19 with an ARDS, especially in older subjects. This reinforces the rationale of modulating rather than suppressing immune responses in these patients.

Immunosuppression (IS) and autoimmune disease (AD) are prevalent in patients with severe coronavirus disease 2019 (COVID-19), but their impact on its clinical course is unknown. We investigated relationships between IS, AD, and outcomes in patients hospitalized with COVID-19. Data on consecutive admissions for COVID-19 were extracted retrospectively from medical records. Patients were assigned to one of four cohorts, according to whether or not they had an AD (AD and NAD) or were immunosuppressed (IS and NIS). The primary endpoint was development of severe acute respiratory distress syndrome (ARDS); secondary endpoints included death, and a composite of mechanical ventilation (MV) or death. A total of 789 patients were included: 569 (72.1%) male, 76 (9.6%) with an AD, and 63 (8.0%) with IS. Relative to the NIS-NAD cohort, patients in the IS-AD cohort had a significantly reduced risk of severe ARDS (adjusted hazard ratio [aHR] 0.42; 95% confidence interval [CI] 0.23-0.80; p = 0.008). No significant relationships between IS or AD status and either death or the composite of MV and death were identified, although a trend towards higher mortality was identified in the IS-NAD cohort (aHR vs NIS-NAD 1.71; 95% CI 0.94-3.12; p = 0.081). Patients in this cohort also had higher median serum levels of interleukin-6 compared with IS-AD patients (98.2 vs 21.6 pg/mL; p = 0.0328) and NIS-NAD patients (29.1 pg/mL; p = 0.0057). In conclusion, among patients hospitalized with COVID-19, those receiving immunosuppressive treatment for an AD may have a reduced risk of developing severe ARDS.

Objective: To assess the effectiveness of steroid injection (local treatment, LT) into the digital flexor tendon sheath of dactylitis in psoriatic arthritis (PsA) patients as compared with systemic treatment (ST)., Methods: Forty-six PsA patients with a total of 73 dactylitic fingers were assessed in an observational, multicentre, prospective study by the Leeds Dactylitis Index basic (LDI-b) score and evaluated for local pain (visual analogue scale-VAS pain) and functional impairment (VAS-FI). Steroid injection was proposed to all patients. Patients refusing LT were treated with oral NSAIDs. Both the groups continued baseline csDMARDs and/or corticosteroids therapy. The clinical outcomes were measured at baseline, 1 month (T1) and 3 months (T3)., Results: The reduction of VAS-pain, VAS-FI and LDI-b values was statistically significant higher in the LT group (24 patients, 38 dactylitic fingers) as compared with the ST group (22 patients, 35 dactylitic fingers), both at T1 (p < 0.001, p < 0.001 and p = 0.008, respectively) and at T3 (p < 0.001, p < 0.001 and p < 0.001, respectively). A clinically meaningful treatment response (defined as a contemporary reduction of at least 5 points in VAS-pain and VAS-FI or as values of VAS-pain and VAS-FI were both ≤ 2) was observed at T1 in 33 (87%) digits in LT group and in 6 (17%) digits in ST group (p < 0.001). At T3, clinical response improved significantly in both the groups, with significant difference (94% vs 31%, p < 0.001)., Conclusions: For the first time, we show the effectiveness of steroid injection into the digital flexor tendon sheath in improving clinical aspects of hand psoriatic dactylitis. Key Points • Therapy with steroid injection (local treatment, LT), into the digital flexor tendon sheath for the treatment of active dactylitis in psoriatic arthritis patients, is more effective when compared with systemic treatment (ST) alone. • The reduction of VAS-pain, VAS-functional impairment (VAS-FI) and Leeds Dactylitis Index basic values was statistically significant higher in the LT group as compared with the ST group, both at T1and at T3. • A clinically meaningful response was observed at T1 in 87% of digits of patients treated with steroid injection and in 17% of digits of the systemic treatment group (p < 0.001). At T3, clinical response improved significantly in both the groups, with significant difference. • For the first time, findings from this study show that the use of steroid injections into the digital flexor tendon sheath for psoriatic dactylitis could be an effective and safe first-line therapy for psoriatic dactylitis.

SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) syndrome is a poorly known disease with cutaneous and osteo-articular manifestations requiring a multidisciplinary care. The aim of this study was to review the case reports that have described oral manifestations in patients suffering for this syndrome. A systematic review of case reports was performed on PubMed and Science Direct on January 2020 among all the articles dealing with the disease. In vitro, preclinical, and clinical studies have not been included to select only the case reports. Eighteen articles, published between 1999 and 2019, were included. All the patients presented mandibular osteomyelitis or sclerosis, associated with various other symptoms such as trismus, temporomandibular joint arthritis, or dysphagia. The data highlight the high variability in the disease's manifestations between people and also in the treatments applied. Knowing the orofacial signs of the SAPHO syndrome, the dental surgeon has a crucial role in the diagnosis procedure and must take place in the multidisciplinary medical team involved in the patient following. Some care adaptations are needed for oral interventions in these patients, depending on their treatments and their handicap. Key Points • Orofacial manifestations of SAPHO syndrome mainly occur on the mandible. • In cases of mandible sclerosis, decorticalization surgeries may be performed. • Oral care are encouraged, especially the preventive treatments to limit the necessity of surgeries. • The complexity in the management of patients suffering for a SAPHO syndrome concerns the oral manifestations, the patient general health and the treatments he has to take every day.

Introduction: Biologic disease-modifying antirheumatic drugs (bDMARDs) play a pivotal role in the treatment of psoriatic arthritis (PsA). Despite this, their discontinuation due to inefficacy or adverse events is often observed. The aims of this study are to describe retention rates and treatment trends of anti-TNFα, anti-IL17, and anti-IL12/23R agents in patients with PsA and to identify factors associated with bDMARDs discontinuation in a real-world clinical setting., Methods: A retrospective cohort study based on the analysis of the three Italian prescription cohorts of patients with PsA has been performed. Survival analysis was performed using Kaplan-Meier curves and Cox proportional-hazards model., Results: During the follow up, which lasted 25.5 (12-60) months, 68 patients discontinued a bDMARD: 13 for primary failure, 12 for secondary failure, 15 for adverse events, 5 for remission, 12 because of lost at follow-up, and 11 for other causes. Cox proportional-hazards demonstrated that a shorter disease duration (HR 0.994991, 95% CI 0.9910336-0.9989647, p = 0.014) and first-line bDMARD (HR 0.5090986, 95% CI 0.3073519-0.8432722, p = 0.009) have a protective role on bDMARD retention rate, while the multivariable analysis failed in demonstrating an independent protective role of male sex on drug retention rate (p = 0.083). No significant differences in retention rate have been found regarding biologic drugs, combination therapy or monotherapy, and class of bDMARD (anti-TNFα or anti-pIL12/23R and anti-IL-17)., Conclusions: This study shows that a shorter disease duration and treatment with a first-line bDMARD are predictors of bDMARDs retention rate, further highlighting the importance of early diagnosis of PsA. Key Points • No significant difference in retention among patients treated with anti-IL17A, anti-IL12/23R, and anti-TNFα agents has been demonstrated. • A shorter disease duration and first-line bDMARD treatment are associated with persistence in biologic treatment.

The city of Rio Grande, located on the right bank of the Patos Estuary, has been severely contaminated by mercury (Hg) due to anthropogenic activities that chiefly began in the eighteenth century. To investigate the natural mercury distribution along the salinity gradient in the estuary, three sediment cores were collected from a region of the estuary that has experienced less anthropogenic impacts, namely its left bank. Our study demonstrates that accumulation of Hg and formation of metal sulfide minerals take place in fine grain sediment horizons within the sampled sediment cores. Mercury immobilization in these sediments occurs via binding to organic matter coatings on fine grain sediment particles, as well as by incorporation into and/or co-precipitation with iron sulfide minerals. The grain size controls over Hg accumulation and sulfide mineral formation were statistically demonstrated using principal component analysis. Different fine particulate sediment deposition patterns occurred at each sampling location, which is attributed to the consequence of hydrological changes in the estuary resulting from navigation infrastructure reforms performed over the past 200 years in the local port (e.g., dredging) and its surroundings. We suggest that the port building and maintenance activities have influenced Hg distributions in the estuarine sediments.

Objective: Despite diffuse digital swelling, dactylitis may sometimes be asymptomatic. The objective of this study was to compare the clinical and ultrasonographic features of symptomatic with asymptomatic psoriatic arthritis (PsA) dactylitis., Methods: One hundred and twenty-five hand dactylitis were evaluated in a multicenter cross-sectional study for the presence of pain, subjective functional limitation, and tenderness (4-points scale) with the calculation of a Leeds Dactylitis Index (LDI) score. Fingers were subsequently investigated using high-frequency ultrasound (US) both in gray-scale (GS) and power Doppler (PD), for the presence and grading of flexor tenosynovitis, soft tissue edema, subcutaneous PD signal (PDUS), extensor tendon involvement, and joints synovitis. Clinical and US characteristics of symptomatic dactylitic fingers were compared with the asymptomatic dactylitic ones., Results: Symptomatic fingers (n = 80) had a significantly lower dactylitis duration compared to asymptomatic fingers (n = 36) (p < 0.001). Values of LDI, patient VAS-pain, and VAS-functional score were significantly higher in fingers with symptomatic dactylitis (p < 0.001 and p = 0.010, respectively). Symptomatic dactylitis had a higher prevalence of flexor tenosynovitis of grade > 2, soft tissue edema and subcutaneous PDUS signal (p < 0.001). Asymptomatic dactylitis showed a greater prevalence of joint synovitis (both in GS and in PD) than symptomatic dactylitis (p < 0.001)., Conclusions: Digital tenderness and pain are linked to US tenosynovitis of grade > 2 and extra synovial abnormalities and conversely asymptomatic dactylitis is associated with joint-based synovitis.Key Points• Digital tenderness and local pain in psoriatic arthritis dactylitis are strongly associated with flexor tenosynovitis of grade> 2, soft tissue edema, and subcutaneous PD signal.• In psoriatic arthritis, asymptomatic dactylitis showed a greater prevalence of joint synovitis than symptomatic dactylitis.• In psoriatic arthritis, ultrasound inflammatory abnormalities are present in about 70% of cold dactylitis which is linked for disease chronicity.• In psoriatic arthritis, the flexor tendon and adjacent soft tissues play a significant role in symptomatic dactylitis.

Patients with psoriatic arthritis (PsA) have an increased prevalence of obesity, but mechanisms underlying this association remain unknown and it is unclear if obesity is the cause or effect of PsA. For PsA patients, comorbid obesity may influence their clinical response to systemic treatment, and especially targeted immunomodulators such as anti-tumor necrosis factor (TNF)α. Weight gain has also been associated with anti-TNFα treatment. Consequently, modification of the therapeutic approach may be needed for patients with an inadequate response to TNFα inhibitors. In recent years, interleukin (IL)-12/IL-23 inhibitors have entered clinical practice as a new class of drug for the treatment of PsA, with some data suggesting a lower effect of body weight on their effectiveness. Recent findings demonstrate effective and sustained responses in patients with PsA to ustekinumab, an IL-12/IL-23 inhibitor. This narrative review critically discusses the link between PsA, obesity, and response to therapy. The current role of ustekinumab in this setting is also discussed.

Objective: Adipokines have been considered in the pathogenesis of the inflammatory processes of psoriatic arthritis (PsA). The main aim of the current study is to investigate possible differences and correlations between adipokines and clinical expression in PsA patients with and without clinical evident psoriasis., Methods: Serum levels of TNF-α, IL-6, leptin, resistin, visfatin, and ghrelin were measured in 80 consecutive PsA patients, 42 PsA patients with clinically evident psoriasis (group 1) and 38 PsA patients sine psoriasis (group 2), fulfilling the CASPAR criteria., Results: Patients of the two groups were not significantly different for levels of TNF-α, IL-6, leptin, resistin, visfatin, and ghrelin. In the entire cohort, a positive association has been shown between leptin levels and female gender (β = 0.3, p = 0.001), BMI (β = 0.8, p < 0.0001), tender joint count (β = 0.23, p = 0.05), and patient pain-VAS score (β = 0.4, p = 0.049). In group 1, serum concentration of leptin was associated with female gender (β = 0.41, p < 0.0001) and BMI (β = 0.6, p = 0.012), whereas in group 2, a positive association was shown between leptin levels and BMI (β = 0.7, p = 0.003) and CRP (β = 0.35, p = 0.012). With regard to resistin, in the multivariate model, only the association between resistin and IL-6 was found (β = 0.33, p = 0.002). The association between resistin and IL-6 was confirmed in group 1 (β = 0.46, p = 0.004) but not in group 2., Conclusions: Until today, the present study represents the first investigating difference in the adipokine pattern between PsA patients with psoriasis and sine psoriasis. We report a strict interplay between leptin, female gender, BMI, and inflammatory activity in overall PsA patients. In PsA patients with clinical evident psoriasis, leptin was associated with female gender and BMI, and a close association between resistin and IL-6 was found. Further, a positive association between leptin levels and BMI and CRP was found in PsA sine psoriasis patients. Further studies are also advocated for clarifying the possible role of these adipokines as laboratory findings or as disease mediators in addressing the different phenotypes of the disease. Key Points •Levels of TNF-α, IL-6, leptin, resistin, visfatin, and ghrelin did not differ between PsA patients with clinical evident psoriasis and PsA sine psoriasis. •There is a strict interplay between leptin, female gender, BMI, and inflammatory activity in PsA. •There is a close association between resistin and IL-6 in PsA patients with clinical evident psoriasis.

The increased cardiovascular (CV) risk is one of the major challenges in the management of patients with psoriatic arthritis (PsA). Recently, EULAR suggested to adapt the already available CV risk algorithms with a 1.5 multiplication factor in all the patients with rheumatoid arthritis (RA), but it is still uncertain if this adaptation could also be applied to patients with PsA. This study aims to evaluate the performance and calibration of the CV risk algorithm ASSIGN and its adaptations for RA (ASSIGN-RA) and according to EULAR recommendations in a cohort of patients with PsA (ASSIGN*1.5). Prospectively, collected data from two Italian cohorts has been analyzed. The discriminatory ability for CV risk prediction was assessed using the areas under the ROC curves. Calibration between predicted and observed events was assessed by Hosmer-Lemeshow (HL) test and calibration plots. For each algorithm, sensitivity and specificity were calculated for low- to high-risk cut-off (20%). One hundred fifty-five patients were enrolled with an observation of 1550 patient/years. Area under the ROC were 0.8179 (95% CI 0.72014 to 0.91558) for ASSIGN, 0.8160 (95% CI 0.71661 to 0.91529) for ASSIGN-RA, and 0.8179 (95% CI 0.72014 to 0.91558) for ASSIGN*1.5. HL tests did not demonstrate poor model fit for none of the algorithms. Discriminative ability and calibration were not improved by adaptation of the algorithms according to EULAR recommendations. Up to 20% of CV events occurred in patients at "low risk". No difference in performance has been observed between ASSIGN, Progetto CUORE, and QRISK2. ASSIGN could represent a useful tool in predicting CV risk in patients with PsA. Adaptation for RA or according to EULAR recommendations did not show any further improvement in performance and calibration.

Objectives: To explore the link between ultrasonographic features of dactylitis in psoriatic arthritis (PsA) and symptoms, digital tenderness and duration of dactylitis., Methods: Forty-eight cases of PsA dactylitis were investigated using high frequency ultrasound (US) both in grey scale (GS) and Power Doppler (PD), evaluating the presence and the degree of flexor tenosynovitis, peri-tendinous oedema, subcutaneous PD, extensor tendon involvement, GS synovitis and intra-articular PD signal (PDS) of the involved digits. Patients were compared according to the presence of local pain and digital tenderness, the duration of dactylitis and the concomitant treatment., Results: The presence of pain/tenderness was positively associated with US GS flexor tenosynovitis of grade > 2 (p < 0.001), PD-flexor tenosynovitis (p < 0.001), peri-tendinous oedema (p < 0.001) and subcutaneous PDS (p < 0.001); moreover, it was negatively associated with GS synovitis (p < 0.001) and intra-articular PD (p < 0.001). The same positive and negative association with US findings were found comparing patients with duration of dactylitis shorter or longer than the median (24 weeks) (p < 0.001 for all comparisons)., Conclusions: Pain and digital tenderness are linked to dactylitis duration and earlier lesions are associated with extra synovial inflammatory changes. These findings suggest a hitherto unappreciated extra synovial basis for symptoms in PsA dactylitis.

Objective: To compare the performance of different knee osteoarthritis (OA) classification criteria in a subsample of subjects of ELSA-Brasil Musculoskeletal cohort (ELSA-Brasil MSK) in comparison with the clinical-radiographic evaluation of an experienced rheumatologist., Method: A cross-sectional study of the diagnostic accuracy of different knee OA classification criteria: radiographic OA, symptomatic OA, clinical and clinical-radiographic criteria of the American College of Rheumatology (ACR), and the definition proposed by the National Institute for Health and Care Excellence (NICE), UK. The study also evaluated some alternative definitions of OA including a combination of criteria. In total, 250 subjects participated. Only one knee per subject was included. When both or none of the knees were affected, one knee was randomly selected for analysis. OA prevalence, sensitivity, specificity, positive and negative predictive values, and accuracy were presented (CI 95%; α = 5%)., Results: The mean age was 56.1 years (SD = 8.7), 48.8% female, and 39.2% presented knee OA according to the rheumatologist. The sensitivity and the specificity of radiographic OA were 51% and 96.7%, respectively, while the NICE definition showed 57.0% and 76.3%, respectively. The other OA criteria showed good levels of specificity, but the levels of sensitivity were below 30%. Considering NICE and/or X-ray result in combination, the sensitivity increased (73.4%), while the specificity reduced slightly (73.0%) in relation to the original NICE definition., Conclusions: Radiographic OA showed the best performance, followed by NICE definition, especially in combination with X-ray results.

Autoimmune diseases and autoinflammatory diseases have a number of similar etiopathogenetic and clinical characteristics, including genetic predisposition and recurrent systemic inflammatory flares. The first phase of ADs involves innate immunity: by means of TLRs, autoantigen presentation, B and T cell recruitment and autoantibody synthesis. The second phase involves adaptive immunity, a self-sustaining process in which immune complexes containing nucleic acids and autoantibodies activate self-directed inflammation. The link between autoimmunity and autoinflammation is IL-1ß, which is crucial in connecting the innate immune response due to NLR activation and the adaptive immune responses of T and B cells. In conclusion, although ADs are still considered adaptive immunity-mediated disorders, there is increasing evidence that innate immunity and inflammasomes are also involved. The aim of this review is to highlight the link between the innate and adaptive immune mechanisms involved in autoimmune diseases.

The aim of this study was to evaluate the prevalence of MetS and its components and the level of serum uric acid in patients with PsA and in those with PsA sine psoriasis. A secondary aim of the study was to investigate on correlations of MetS in all study population. Consecutive PsA patients underwent assessment of disease activity and metabolic parameters. Blood samples were collected after 12 h of overnight fasting and analyzed for glucose, lipid profile, serum uric acid, and acute-phase reactants. The NCEP-ACT III criteria were used to identify subjects with MetS. Forty-two patients (52.5%) were classified as having PsA with clinically evident psoriasis (group 1) and 38 (47.5%) as having PsA sine psoriasis (group 2). Group 1, when compared to group 2, showed a significant increase for the frequency of MetS (p = 0.006) and for mean values of diastolic blood pressure (p = 0.0116) and of serum uric acid (p = 0.04). We then aimed at defining determinants of MetS in the entire study population. In the multivariate analysis, three variables reached statistical significance: presence of psoriasis (OR 0.14; p = 0.01), increase of one unit of BMI (OR 1.26; p = 0.001), and smoking habit (OR 5.93; p = 0.02). In our study, the occurrence of MetS and mean levels of serum uric acid were higher in PsA patients with clinical evident psoriasis compared to sine psoriasis PsA. The results also show the potential role of BMI, psoriasis, and smoking as important determinants in the development of MetS in PsA patients.

The current prospective observational study aimed to evaluate the long-term (24 months), real-life effectiveness of ustekinumab in psoriatic arthritis (PsA). Consecutive patients with moderate-severe PsA and active psoriasis who begun ustekinumab treatment were evaluated prospectively (January 2015-March 2017). Clinimetric scores and biochemical values were assessed at baseline (T0), at 6 (T6), 12 (T12), and 24 (T24) months. Friedman test and generalized linear models were used to compare variables over time. Regression analysis to identify determinants of minimal disease activity (MDA) at T6 and of treatment discontinuation was conducted. Sixty-five patients (43.1% men; age 49.4 ± 11.6 years) were enrolled; ustekinumab was prescribed as a first (20%), second (33.8%), third (26.5%), fourth (15.4%), or fifth (4.6%) line biological therapy. Significant decrease in tender/swollen joints, Visual Analogue Scale of pain (VASp) and general health (VASgh), Disease Activity in PsA (DAPSA), Psoriasis Area Severity Index (PASI), Leeds Enthesitis Index (LEI), Health Assessment Questionnaire modified for spondyloarthritis (HAQ-S), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) was achieved. MDA was reached by 30.7, 47.0, and 34.0% of patients respectively at T6, T12, and T24. In multivariable models, mono-oligoarthritis was independently associated to MDA at T6 (OR 9.02; 95% CI 1.41, 57.71), while baseline CRP (OR 1.12; 95% CI 1.00, 1.26) and LEI (OR 0.50; 95% CI 0.25, 0.97) to ustekinumab discontinuation. More patients used disease-modifying antirheumatic drugs at T0 (35.3%) than at T24 (8.5%). Only nine episodes of infection and no serious adverse events were registered. In a real-life clinical setting, ustekinumab was safe and effective in PsA. Comedication tapering was often possible.

Psoriatic arthritis (PsA) is an inflammatory arthropathy, associated with skin and/or nail psoriasis. Real world data on efficacy and safety of TNF-α blockers in the elderly with PsA are lacking. The aim of this study was to evaluate the effectiveness, through the achievement of minimal disease activity (MDA), drug discontinuation rate, and safety in elderly patients with PsA on TNF-α blockers. A multicenter, observational study was carried out in four Italian centers. The assessment of disease activity and safety were performed at the start of anti-TNF-α (T0), at 6 months (T6) and at 12 months (T12). A total of 145 PsA patients were included in the study. At baseline 68 (46.9%) patients were on etanercept, 60 (41.3%) on adalimumab, 11 (7.6%) on golimumab, and 6 (4.1%) on infliximab. All the variables concerning PsA activity showed a statistically significant improvement when comparing T6 and T12 with T0. After 6 and 12 months of therapy, respectively, 31 (22.6%) and 71 (51.8%) patients achieved MDA (p < 0.001). The drug discontinuation rate was 5.5% with a mean of 6.8 months (range 2-10 months), and it was due to lack of efficacy, adverse events, and lost to follow-up. Nine patients (6.2%) reported the onset of mild infections resolved with antimicrobial specific oral regimen without therapy interruption. TNF-α blockers are effective in the achievement of a low disease status and safe in elderly patients with PsA. Therefore, age should not be considered a limitation to their use.

Psoriatic arthritis (PsA) is a chronic inflammatory joint disease affecting around 40% of psoriasis patients. Minimal disease activity (MDA) criteria have been proposed to identify a state of low disease activity, one of the principal goals of treatment for psoriatic disease. This study investigated treatment with ustekinumab (UST) in the context of a real-world setting. Thirty-four PsA patients who had failure or inadequate response to conventional synthetic disease-modifying antirheumatic drugs or to anti-tumour necrosis factor alpha were enrolled. Demographic and clinical features, MDA criteria, and the impact of psoriatic skin manifestations on patients' quality of life (QoL) using the dermatology life quality index (DLQI) questionnaire were evaluated at baseline and after 24-week treatment. Adverse events were recorded. At week 24, 70.5% of patients (n = 24) achieved MDA. A sub-analysis of dermatological indices of the MDA criteria showed that the psoriasis area severity index score was significantly improved and body surface area was significantly decreased at 24 weeks compared with that at baseline (both p < 0.001). For the rheumatologic indexes, tender joint count, swollen joint count, and tender entheseal points were all significantly improved at 24 weeks of therapy (all p < 0.01 vs. baseline). Mean DLQI value decreased approximately fourfold, and there were no safety concerns. The achievement of MDA as well as the significant improvement in DLQI and lack of adverse events in the context of a real-life setting shown here confirms the efficacy and safety of UST in PsA.

Introduction and Hypothesis: The objective was to determine the prevalence of urinary incontinence (UI) and factors associated in a sample of Brazilian middle-aged women., Methods: A cross-sectional study was conducted between September 2012 and June 2013 with 749 women. UI was defined as any complaint of involuntary loss of urine. The independent variables were sociodemographic data and health-related habits and problems. Statistical analysis was carried out using Chi-squared test and Poisson regression., Results: The mean age was 52.5 (±4.4) years. The prevalence of UI was 23.6 %. Of these, 48 (6.4 %) had stress urinary incontinence, 59 (7.8 %) urinary urgency, and 70 (9.5 %) had mixed urinary incontinence. In the final statistical model, self-perception of health as fair/poor/very poor (PR: 1.90; 95 % CI, 1.45-2.49; P < 0.001), ≥1 vaginal deliveries (PR: 1.84; 95 % CI, 1.35-2.50; P < 0.001), higher body mass index (PR: 1.04; 95 % CI, 1.02-1.06; P = 0.001), vaginal dryness (PR: 1.60; 95 % CI, 1.23-2.08; P = 0.001), current or previous hormone therapy (PR: 1.38; 95 % CI, 1.06-1.81; P = 0.019), pre-/perimenopause (PR: 1.42; 95 % CI, 1.06-1.91; P = 0.021), and previous hysterectomy (PR: 1.41; 95 % CI, 1.03-1.92; P = 0.031) were associated with a greater prevalence of UI. Current or previous use of soy products to treat menopausal symptoms was associated with a lower prevalence of UI (PR: 0.43; 95 % CI, 0.24-0.78; P = 0.006)., Conclusions: Several factors are associated with UI in middle-aged Brazilian women. The results highlight the importance of carrying out interventions aimed at reducing modifiable factors.

To develop quantitative imaging biomarkers of synovial tissue perfusion by pixel-based contrast-enhanced ultrasound (CEUS), we studied the relationship between CEUS synovial vascular perfusion and the frequencies of pathogenic T helper (Th)-17 cells in psoriatic arthritis (PsA) joints. Eight consecutive patients with PsA were enrolled in this study. Gray scale CEUS evaluation was performed on the same joint immediately after joint aspiration, by automatic assessment perfusion data, using a new quantification approach of pixel-based analysis and the gamma-variate model. The set of perfusional parameters considered by the time intensity curve includes the maximum value (peak) of the signal intensity curve, the blood volume index or area under the curve, (BVI, AUC) and the contrast mean transit time (MTT). The direct ex vivo analysis of the frequencies of SF IL17A-F + CD161 + IL23 + CD4 + T cells subsets were quantified by fluorescence-activated cell sorter (FACS). In cross-sectional analyses, when tested for multiple comparison setting, a false discovery rate at 10%, a common pattern of correlations between CEUS Peak, AUC (BVI) and MTT parameters with the IL17A-F + IL23 + - IL17A-F + CD161 + - and IL17A-F + CD161 + IL23 + CD4 + T cells subsets, as well as lack of correlation between both peak and AUC values and both CD4 + T and CD4 + IL23 + T cells, was observed. The pixel-based CEUS assessment is a truly measure synovial inflammation, as a useful tool to develop quantitative imaging biomarker for monitoring target therapeutics in PsA.

Psoriasis frequency ranges from 1 to 3 % in white population, and arthritis occurs in 10-40 % of psoriasis patients, representing a relevant health issue. Psoriatic arthritis (PsA) is an inflammatory arthropathy, associated with psoriasis, in which ocular-, intestinal-, metabolic-, and cardiovascular-related manifestations can variably coexist. In order to favor early PsA and psoriasis diagnosis, it is crucial to rule out other conditions that can resemble the disease and delay appropriate therapeutic approach. Therefore, the aim of this review is to focus on PsA and psoriasis differential diagnosis.

Psoriatic arthritis (PsA) is an inflammatory rheumatic disorder occurring in patients with psoriasis. Several studies have shown an association between Psa and traditional atherosclerotic risk factors. We evaluated the relationship between small dense low-density lipoproteins particles (sd-LDL) a risk marker for atherosclerosis, sub-clinical atherosclerosis and PsA in a group of 50 patients with PsA and in 100 controls. Cholesterol, high-density lipoproteins (HDL), low-density lipoproteins (LDL), triglycerides, insulin, homeostasis model assessment (HOMA), Apo B, and sd-LDL have been measured. LDL particle separation was performed and seven LDL subfractions were obtained, LDL score (percentage of sd-LDL) and mean LDL particle size were calculated. PsA patients and control group differ significantly (p < 0.001) in triglycerides values (119.3 ± 52.0 vs 90.7 ± 40.7 mg/dL), Apo B (1.1 ± 0.2 vs 0.9 ± 0.1 g/L), insulin (8.9 ± 4.9 vs 5.8 ± 3.2 mU/L), HOMA (2.2 ± 1.7 vs 1.3 ± 0.8), BMI (27.7 ± 3.3 vs 25.8 ± 3.8). LDL score is significantly higher in PsA as compared to control (9.0 ± 10.7 vs 2.9 ± 4.7 mg/dL); and mean LDL size is significantly lower in PsA than control (268.1 ± 4.6 vs 271.2 ± 2.7 Å). These differences were confirmed when stratifying PsA patients for treatment and for disease activity. LDL score and LDL diameter significantly were correlated with the carotid IMT in patients with PsA. These findings show a novel relationship between LDL score and mean LDL size with PsA diagnosis and with sub-clinical atherosclerosis. Sd-LDL gives potentially useful information in the risk assessment for atherosclerotic disease in PsA patients.

Activated sludge systems are prone to be affected by foaming occurrences causing the sludge to rise in the reactor and affecting the wastewater treatment plant (WWTP) performance. Nonetheless, there is currently a knowledge gap hindering the development of foaming events prediction tools that may be fulfilled by the quantitative monitoring of AS systems biota and sludge characteristics. As such, the present study focuses on the assessment of foaming events in full-scale WWTPs, by quantitative protozoa, metazoa, filamentous bacteria, and sludge characteristics analysis, further used to enlighten the inner relationships between these parameters. In the current study, a conventional activated sludge system (CAS) and an oxidation ditch (OD) were surveyed throughout a period of 2 and 3 months, respectively, regarding their biota and sludge characteristics. The biota community was monitored by microscopic observation, and a new filamentous bacteria index was developed to quantify their occurrence. Sludge characteristics (aggregated and filamentous biomass contents and aggregate size) were determined by quantitative image analysis (QIA). The obtained data was then processed by principal components analysis (PCA), cross-correlation analysis, and decision trees to assess the foaming occurrences, and enlighten the inner relationships. It was found that such events were best assessed by the combined use of the relative abundance of testate amoeba and nocardioform filamentous index, presenting a 92.9 % success rate for overall foaming events, and 87.5 and 100 %, respectively, for persistent and mild events.

Adult-onset Still's disease (AOSD) is a systemic inflammatory condition of unknown aetiology characterized by typical episodes of spiking fever, evanescent rash, arthralgia, leukocytosis and hyperferritinemia. Given the lack of data in Italian series, we promote a multicentric data collection to characterize the clinical phenotype of Italian patients with AOSD. Data from 245 subjects diagnosed with AOSD were collected by 15 centres between March and May 2013. The diagnosis was made following Yamaguchi's criteria. Data regarding clinical manifestations, laboratory features, disease course and treatments were reported and compared with those presented in other published series of different ethnicity. The most frequent features were the following: arthritis (93 %), pyrexia (92.6 %), leukocytosis (89 %), negative ANA (90.4 %) and neutrophilia (82 %). As compared to other North American, North European, Middle Eastern and Far Eastern cohorts, Italian data show differences in clinical and laboratory findings. Regarding the treatments, in 21.9 % of cases, corticosteroids and traditional DMARDs have not been able to control the disease while biologics have been shown to be effective in 48 to 58 patients. This retrospective work summarizes the largest Italian multicentre series of AOSD patients and presents clinical and laboratory features that appear to be influenced by the ethnicity of the affected subjects.

Immune system responses in fish are considered as suitable and sensitive biomarkers for monitoring aquatic pollution. However, a clear knowledge gap persists in the literture on the immunotoxic potential of engineered nanoparticles toward aquatic organisms such as fish. Employing major enzymatic- (glutathione reductase, GR; glutathione peroxidase, GPX; glutathione sulfo-transferase, GST; catalase, CAT) and thiol- (non-protein thiols, NP-SH; total glutathione, TGSH)-based defense biomarkers, this study assessed the response of phagocytes isolated from peritoneum (P-phagocytes), gill (G-phagocytes), head kidney (HK-phagocytes), and spleen (S-phagocytes) of European eel (Anguilla anguilla L.) to silica-coated magnetite particles (Fe3O4@SiO2/SiDTC, hereafter called IONP; size range: 82 ± 21 to 100 ± 30 nm; 2.5 mg L(-1)) alone and IONP and mercury (Hg; 50 μg L(-1)) concomitant exposures. Responses of previous biomarkers were studied in P-phagocytes, G-phagocytes, HK-phagocytes, and S-phagocytes collected during 0, 2, 4, 8, 16, 24, 48, and 72 h of exposures. Contingent to hour of exposure to IONP, Hg, and IONP + Hg GST, GPX, CAT, NP-SH, and TGSH exhibited their differential responses in all the phagocytic cells considered. In particular, under IONP exposure, the potential occurrence of the GSH-independent antioxidant defense was indicated by the observed herein inhibition in the enzymatic- and thiol-based defense in A. anguilla phagocytes. In contrast, the response of P-, G-, HK-, and S-phagocytes to the increasing Hg exposure period reflected an increased detoxification activity. Notably, the occurrence of an antagonism between IONP and Hg was depicted during late hours (72 h) under IONP + Hg concomitant exposure, where elevations in the defense biomarkers were depicted. Overall, the P-, G-, HK-, and S-phagocytic cells exhibited a differential induction in the studied enzymes and thiols to counteract impacts of IONP, Hg, and IONP + Hg concomitant exposures. Future studies on the fish immunotoxicity responses to IONP exposure in multi-pollution conditions can be benefited with the major outcomes of the present study.

To evaluate the impact of anti-TNF-α therapy on the body weight of rheumatoid arthritis (RA) patients following 24 months of treatment. Data were collected on all RA patients included in the Veneto Region's Registry of Biological Therapy from January 2007 to July 2012. Inclusion criteria were: start of monotherapy with adalimumab, etanercept, or methotrexate, no previous use of biologic therapy, and at least 24 months of treatment. At baseline, 12, and 24 months, each patient completed a questionnaire about physical activity, smoking, alcohol, and food habits. One hundred and thirty-one RA patients in monotherapy with etanercept (n = 47), adalimumab (n = 44), and methotrexate (n = 40) were enrolled for this study. After 24 months of therapy, there was an increase of weight only in patients treated with anti-TNF-α. Patients on etanercept and adalimumab therapy showed a risk to gain weight six times greater compared to those on methotrexate therapy. The results of present study show that the use of anti-TNF-α in RA patients can be associated to a significant increase of body weight. This increase is not shown in patients under treatment with methotrexate. A more careful evaluation of weight changes needs to be considered in RA patients under anti-TNF-α treatment.

The association between radiographic osteoarthritis (OA) and symptoms is inconsistent and variable according to each joint. The purpose of this study is to understand the relation between radiographic OA features, pain, function and quality of life, in knee and hip joints. A cross-sectional study was performed using information from EPIPorto cohort. Data was obtained by interview using a structured questionnaire on social, demographic, behavioural and clinical data. Pain was assessed using a pain frequency score (regarding ever having knee pain, pain in the last year, in the last 6 months and in the last month). Quality of life was evaluated with Short Form 36 (SF-36) and function disability with the Lequesne knee and hip indexes. Radiographic knees and hips were classified using the Kellgren-Lawrence score (KL 0-4). Linear regression and proportional odds ratios estimated the association between radiographic features, pain, function and quality of life. In our study, symptomatic OA (KL ≥ 2 plus joint pain) was 26.0 % in knee and 7.0 % hip joints. In knee, the increase on radiographic score increased the odds to have a higher pain frequency score [1.58 (95 % CI = 1.27, 1.97)] and was associated [adjusted β (95 % CI)] with worst general health [-3.05 (-5.00, -1.09)], physical function [-4.92 (-7.03, -2.80)], role-physical [-4.10 (-8.08, -0.11)], bodily pain [-2.96 (-5.45, -0.48)] and limitations in activities of daily living [0.48 (0.08, 0.89)]. Regarding hip, no significant associations were found between the severity of radiographic lesions and these measures. Radiographic lesions in knee were associated with higher complaints, as far as pain and functional limitations are concerned, compared with hip.

The pediatric syndrome characterized by periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) and adult Behçet's disease share some clinical manifestations and are both polygenic autoinflammatory disorders with interleukin-1β showing to play a pivotal role. However, the diagnosis is mostly clinical and we hypothesize that specific criteria may be addressed differently by different physicians. To determine the diagnostic variability, we compared the answers of 80 patients with a definite diagnosis of Behçet's disease (age 42.1 ± 13.7 years) obtained by separate telephone interviews conducted by a rheumatologist, a pediatrician, and an internist working largely in the field of autoinflammatory disorders. Questions were related to the age of symptom onset, the occurrence of recurrent fevers during childhood, and the association with oral aphthosis, cervical adenitis and/or pharyngitis, previous treatments, possible growth impairment, the time lapse between PFAPA-like symptoms and the onset of Behçet's disease, and the occurrence of Behçet-related manifestation during childhood. The rheumatologist identified 30 % of patients with Behçet's disease fulfilling PFAPA syndrome diagnostic criteria, compared to the pediatrician and the internist identifying 10 and 7.5 %, respectively. Most of the patients suffered from recurrent oral aphthosis in childhood also without fever (50, 39, and 48 % with each interviewer), yet no patient fulfilled the Behçet's disease diagnostic criteria. Our data suggest that physician awareness and expertise are central to the diagnosis of autoinflammatory disorders through an accurate collection of the medical history.

Unlabelled: The risks of fracture were calculated in 402 postmenopausal Brazilian women by FRAX with or without the inclusion of bone densitometry values. The correlation between the risk of major osteoporosis fracture or hip fracture calculated by FRAX with or without BMD was similar in this population, 0.76 and 0.64, respectively., Objective: The objective of this study is to evaluate the degree of agreement between the 10-year fracture risk in postmenopausal Brazilian women, calculated using the WHO Fracture Risk Assessment Tool (FRAX)-Brazil, with and without the inclusion of bone mineral density (BMD) values., Methods: A cross-sectional study was conducted with 402 postmenopausal women (≥40 years) who had undergone bone densitometry prior to initiating any pharmacological treatment for osteopenia or osteoporosis. The risks of a major osteoporosis fracture or hip fracture were calculated according to FRAX-Brazil either using clinical risk factors alone or with the inclusion of BMD value. The tests used were intraclass correlation coefficient, Mann-Whitney test, and univariate linear regression analysis., Results: When the patients were classified according to the cutoff point defined as determining a high risk of a major osteoporosis fracture (≥20 %), 0.75 % were defined as high risk when BMD values were included and 1 % when they were not. With respect to the hip, 5.22 % were defined as having a high risk of fracture (≥3 %) when BMD values were included and 11.44 % when they were not. Intraclass correlation coefficient between the FRAX-Brazil assessed risk with and without the inclusion of BMD values was 0.76 (95 % CI 0.716-0.799) for a major osteoporosis fracture and 0.64 (95 %CI 0.583-0.698) for a hip fracture., Conclusion: The correlation found for the FRAX-Brazil score obtained with and without the inclusion of BMD values was good for the risk of a major osteoporosis fracture and moderate for the risk of a hip fracture. The fracture risk calculated was similar in this population irrespective of whether or not BMD values were included in the algorithm.

The purpose of the study was to assess the relationship of the continuous mode contrast-enhanced harmonic ultrasound (CEUS) imaging with the histopathological and immunohistochemical (IHC) quantitative estimation of microvascular proliferation on synovial samples of patients affected by sustained psoriatic arthritis (PsA). A dedicated linear transducer was used in conjunction with a specific continuous mode contrast enhanced harmonic imaging technology with a second-generation sulfur hexafluoride-filled microbubbles C-agent. The examination was carried out within 1 week before arthroscopic biopsies in 32 active joints. Perfusional parameters were analyzed including regional blood flow (RBF); peak (PEAK) of the C-signal intensity, proportional to the regional blood volume (RBV); beta (β) perfusion frequency; slope (S), representing the inclination of the tangent in the origin; and the refilling time (RT), the reverse of beta. Arthroscopic synovial biopsies were targeted in the hypervascularity areas, as in the same knee recesses assessed by CEUS; the synovial cell infiltrate and vascularity (vessel density) was evaluated by IHC staining of CD45 (mononuclear cell) and CD31, CD105 (endothelial cell) markers, measured by computer-assisted morphometric analysis. In the CEUS area examined, the corresponding time-intensity curves demonstrated a slow rise time. Synovial histology showed slight increased layer lining thickness, perivascular lymphomonocyte cell infiltration, and microvascular remodeling, with marked vessel wall thickening with reduction of the vascular lumen. A significant correlation was found between RT and CD31+ as PEAK and CD105+ vessel density; RT was inversely correlated to RBF, PEAK, S, and β. The study demonstrated the association of the CEUS perfusion kinetics with the histopathological quantitative and morphologic estimation of synovial microvascular proliferation, suggesting that a CEUS imaging represents a reliable tool for the estimate of the synovial hypervascularity in PsA.

Vogt-Koyanagi-Harada disease (VKHD) is a multisystemic disorder characterized by granulomatous panuveitis variably combined with T cell-mediated neurologic and cutaneous manifestations. Early and aggressive treatment with systemic corticosteroids is the mainstay of treatment for VKHD. Additional use of immunosuppressants, intravenous immunoglobulins, and tumor necrosis factor-alpha inhibitors can help the most severely affected patients and work as corticosteroid-sparing agents. We report the case of a young woman with relapsing and multiresistant VKHD who demonstrated a stable remission of both uveitis and high-frequency hearing loss following rituximab intravenous administration (1 g. twice, 2 weeks apart, and 6 months later). A complete clinical response was observed 1 month since the first infusion, and no ocular relapses were recorded during the following year; in addition, audiometry showed a high-frequency hearing recovery in the right ear. Further observational studies are required to define the role of CD20 inhibition in the management of VKHD.

The objective of the study was to quantify the transcriptional profile, as the main T cell lineage-transcription factors on synovial fluid (SF) T cells, in relation to SF cytokines and T cell frequencies (%) of psoriatic arthritis (PsA) patients. Reverse phase protein array was employed to identify interleukin (IL)-23Rp19-, FOXP3- and related orphan receptor gamma T (RORγt)- protein and Janus associated tyrosine kinases 1 (JAK1), signal transducer and activator and transcription 1 (STAT1), STAT3 and STAT5 phosphoproteins in total T cell lysates from SF of PsA patients. IL-1β, IL-2, IL-6, IL-21 and interferon (INF)-γ were measured using a multiplex bead immunoassay in SF from PsA patients and peripheral blood (PB) from healthy controls (HC). Frequencies of CD4(+)CD25(-), CD4(+)CD25(high) FOXP3(+) and CD4(+)CD25(high) CD127(low) Treg, and either mean fluorescence intensity (MFI) of FOXP3(+) on CD4(+) Treg or MFI of classic IL-6 receptor (IL-6R) α expression on CD4(+)CD25(-) helper/effector T cells (Th/eff) and Treg cells, were quantified in SF of PsA patients and in PB from HC by flow cytometry (FC). In PsA SF samples, IL-2, IL-21 and IFN-γ were not detectable, whereas IL-6 and IL-1β levels were higher than in SF of non-inflammatory osteoarthritis patients. Higher levels of IL-23R-, FOXP3- and RORγt proteins and JAK1, STAT1, STAT3 and STAT5 were found in total T cells from SF of PsA patients compared with PB from HC. Direct correlations between JAK1 Y1022/Y1023 and STAT5 Y694, and STAT3 Y705 and IL6, were found in SF of PsA patients. Increased proportion of CD4(+)CD25(high) FOXP3(+) and CD4(+)CD25(high) CD127(low) Treg cells and brighter MFI of IL-6Rα were observed both on CD4(+)CD25(high)- and CD4(+)CD25(-) T cells in PsA SF. The study showed a distinctive JAK1/STAT3/STAT5 transcriptional network on T cells in the joint microenvironment, outlining the interplay of IL-6, IL-23, IL-1β and γC cytokines in the polarization and plasticity of Th17 and Treg cells, which might participate in the perpetuation of joint inflammation in PsA patients.

Vogt-Koyanagi-Harada disease (VKHD) is a multisystemic disorder characterized by granulomatous panuveitis with exudative retinal detachments, often associated with neurologic and cutaneous manifestations. Therapy relies mainly on the use of corticosteroids, administrated as oral or intravenous high-dose pulses, and immunosuppressants. However, since macular edema and retinal detachment can often be refractory to systemic therapies, intravitreal triamcinolone acetate has been used successfully. Herein, we report the first case of refractory bilateral panuveitis in a young patient with VKHD successfully treated with dexamethasone intravitreal implant.

The study aimed to assess the genotoxic potential of silica-coated iron oxide nanoparticle functionalized with dithiocarbamate groups (IONP, 100 nm) in vitro exposure alone or its interference with mercury (Hg) co-exposure in the blood of European eel (Anguilla anguilla L.) by evaluating 8-hydroxy-2'-deoxyguanosine (8-OHdG), lipid peroxidation (LPO), and erythrocytic nuclear abnormalities (ENA). Four groups were made: (i) 2 × 10(6) erythrocytes + Roswell Park Memorial Institute-1640 (RPMI-1640) (control), (ii) 2 × 10(6) erythrocytes + IONP (2.5 mg L(-1)), (iii) 2 × 10(6) erythrocytes + Hg (50 μg L(-1)), and (iv) 2 × 10(6) erythrocytes + IONP + Hg. Blood plasma was also processed following the previous exposure conditions. Samplings were performed at 0, 2, 4, 8, 16, 24, 48, and 72 h of exposure. The results revealed significant ENA increases at both early (2, 4, 8) and late (16, 24, 48, 72) hours of exposure to IONP alone. However, IONP exposure combined with Hg co-exposure revealed no ENA increase at 2 h, suggesting that IONP-Hg complex formation is efficient to eliminate the DNA damage induced by individual exposure to IONP or Hg at early hours. Hence, the initial occurrence of antagonism between IONP and Hg was perceptible; however, at late hours of exposure, IONP was unable to mitigate the mercury-accrued negative impacts. Plasma exposure to IONP alone displayed a significant increase in 8-OHdG levels at 2 and 48 h of exposure. However, IONP in combination with Hg co-exposure revealed an increase in 8-OHdG levels at all the exposure length (except 16 h), suggesting that both IONP and Hg independently oxidized DNA. In addition, an additive effect on 8-OHdG levels at both early and late hours, and on LPO only at late hours (except 24 h), suggested that DNA is more susceptible to peroxidative damage than lipid.

Unlabelled: A cross-sectional study was conducted with the purpose of evaluating bone mineral density in HIV seropositive and seronegative climacteric women. HIV infection was negatively associated with bone mineral density in the lumbar spine, Purpose: To assess bone mineral density (BMD) and its associated factors in HIV seropositive and seronegative climacteric women, Methods: A cross-sectional study with 537 women (273 HIV seropositive and 264 HIV seronegative) aged between 40 and 60 years old receiving follow-up care at two hospitals in Brazil. A questionnaire on clinical and sociodemographic characteristics was completed. Laboratory tests were performed, and BMD was measured at the lumbar spine and hip. Statistical analysis was carried out by Yates and Pearson chi-squared tests, Mann-Whitney test, and multiple linear regression., Results: The mean age was 47.7 years in HIV-seropositive women, and 75 % had nadir CD4 above 200, and 77.8 % had viral load below the detection limit. The mean age in the HIV-seronegative women was 49.8 years. The prevalence of low spinal BMD was 14.6 % in the HIV-seropositive and 4.6 % in the HIV-seronegative women (p < 0.01). The prevalence of low BMD at the femoral neck was 5.6 % in HIV-seropositive and 3.3 % in the HIV-seronegative women (p = 0.38). Multiple analyses showed that the factors associated with lower BMD at the spine were being postmenopausal and being HIV-seropositive. Being overweight was associated with a higher BMD. At the femoral neck, factors associated with lower BMD were being postmenopausal and being white. Being overweight and having a greater number of pregnancies were associated with higher BMD CONCLUSIONS: HIV-seropositive women on long-term antiretroviral treatment and in good immunological conditions exhibited low BMD in the spine (L1-L4). However, BMD in the femoral neck was similar to non-infected women.

Autoinflammatory disorders (AIDs) are a novel class of diseases elicited by mutations in genes regulating the homeostasis of innate immune complexes, named inflammasomes, which lead to uncontrolled oversecretion of the proinflammatory cytokine interleukin-1β. Protean inflammatory symptoms are variably associated with periodic fever, depicting multiple specific conditions. Childhood is usually the lifetime in which most hereditary AIDs start, though still a relevant number of patients may experience a delayed disease onset and receive a definite diagnosis during adulthood. As a major referral laboratory for patients with recurrent fevers, we have tested samples from 787 patients in the period September 2007-March 2014, with a total of 1,328 AID-related genes evaluated and a gene/patient ratio of 1.69. In this report, we describe our experience in the clinical approach to AIDs, highlight the most striking differences between child and adult-onset AIDs, and shed an eye-opening insight into their diagnostic process.