Rheumatoid arthritis (RA) is a chronic inflammatory disease that carries high social and economic costs and can lead to permanent disability. RA pathogenesis has not been completely elucidated yet. ...Extracellular vesicles (EVs) are membrane-contained vesicles released by cells playing a role in cell-to-cell communication and they could be involved in different diseases. Evidence on the involvement of EVs in RA is currently inconclusive. Therefore, a systematic review on the role of EVs in RA was performed in order to explore this relationship. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The research was conducted on PubMed, Scopus, and Embase up to March 5, 2020: 41 studies were analyzed out of 674 screened. The total plasmatic and synovial fluid (SF) EV number seems increased in RA as compared with healthy controls. Both RA plasma and SF contained EVs subpopulations of heterogenous origin, especially derived from platelets and immune system cells. No univocal evidence emerged on miRNA expression and EV content profile within RA patients. EVs showed to enhance pro-inflammatory pathways, such as cytokines and chemokine release and TNF blockade seemed to revert this effect. Our work highlights the requirement to standardize study methodologies in order to make results comparable and draw conclusions that remain, at present, unclear.
Vascular thrombosis and pregnancy morbidity represent the clinical manifestations of antiphospholipid syndrome (APS), which is serologically characterized by the persistent positivity of ...antiphospholipid antibodies (aPL). Antiplatelet and anticoagulant agents currently provide the mainstay of APS treatment. However, the debate is still open: controversies involve the intensity and the duration of anticoagulation and the treatment of stroke and refractory cases. Unfortunately, the literature cannot provide definite answers to these controversial issues as it is flawed by many limitations, mainly due to the recruitment of patients not fulfilling laboratory and clinical criteria for APS. The recommended therapeutic management of different aPL-related clinical manifestations is hereby presented, with a critical appraisal of the evidence supporting such approaches. Cutting edge therapeutic strategies are also discussed, presenting the pioneer reports about the efficacy of novel pharmacological agents in APS. Thanks to a better understanding of aPL pathogenic mechanisms, new therapeutic targets will soon be explored. Much work is still to be done to unravel the most controversial issues about APS management: future studies are warranted to define the optimal management according to aPL risk profile and to assess the impact of a strict control of cardiovascular risk factors on disease control.
To our knowledge, no studies so far have investigated the role of pizza and its ingredients in modulating disease activity in rheumatoid arthritis (RA). We assessed this question via a recent ...cross-sectional study including 365 participants from Italy, the birthplace of pizza. Multiple robust linear and logistic regression models were fitted with the tertile consumption categories of each available pizza-related food item/group (i.e., pizza, refined grains, mozzarella cheese, and olive oil) as independent variables, and each available RA activity measure (i.e., the Disease Activity Score on 28 joints with C-reactive protein (DAS28-CRP), and the Simplified Disease Activity Index (SDAI)) as the dependent variable. Stratified analyses were carried out according to the disease severity or duration. Participants eating half a pizza >1 time/week (vs. ≤2 times/month) reported beneficial effects on disease activity, with the significant reductions of ~70% (overall analysis), and 80% (the more severe stratum), and the significant beta coefficients of -0.70 for the DAS28-CRP, and -3.6 for the SDAI (overall analysis) and of -1.10 and -5.30 (in long-standing and more severe RA, respectively). Among the pizza-related food items/groups, mozzarella cheese and olive oil showed beneficial effects, especially in the more severe stratum. Future cohort studies are needed to confirm this beneficial effect of pizza and related food items/groups on RA disease activity.
To our knowledge, no studies have investigated the relationship between a posteriori dietary patterns (DPs)-representing current dietary behavior-and disease activity in patients with rheumatoid ...arthritis (RA). We analyzed data from a recent Italian cross-sectional study including 365 RA patients (median age: 58.46 years, 78.63% females). Prevalent DPs were identified through principal component factor analysis on 33 nutrients. RA activity was measured according to the Disease Activity Score on 28 joints (DAS28) and the Simplified Disease Activity Index (SDAI). Single DPs were related to disease activity through linear and logistic regression models, adjusted for the remaining DPs and confounders. We identified five DPs (~80% variance explained). Among them, Vegetable unsaturated fatty acids (VUFA) and Animal unsaturated fatty acids (AUFA) DPs were inversely related to DAS28 in the overall analysis, and in the more severe or long-standing RA subgroups; the highest score reductions (VUFA: 0.81, AUFA: 0.71) were reached for the long-standing RA. The SDAI was inversely related with these DPs in subgroups only. This Italian study shows that scoring high on DPs based on unsaturated fats from either source provides independent beneficial effects of clinical relevance on RA disease activity, thus strengthening evidence on the topic.
To assess the efficacy of belimumab in joint and skin manifestations in a nationwide cohort of patients with SLE.
All patients with skin and joint involvement enrolled in the BeRLiSS cohort were ...considered. Belimumab (intravenous, 10 mg/kg) effectiveness in joint and skin manifestations was assessed by DAS28 and CLASI, respectively. Attainment and predictors of DAS28 remission (<2.6) and LDA (≥2.6, ≤3.2), CLASI = 0, 1, and improvement in DAS28 and CLASI indices ≥20%, ≥50%, and ≥70% were evaluated at 6, 12, 24, and 36 months.
DAS28 < 2.6 was achieved by 46%, 57%, and 71% of patients at 6, 12, and 24 months, respectively. CLASI = 0 was achieved by 36%, 48%, and 62% of patients at 6, 12, and 24 months, respectively. Belimumab showed a glucocorticoid-sparing effect, being glucocorticoid-free at 8.5%, 15.4%, 25.6%, and 31.6% of patients at 6, 12, 24, and 36 months, respectively. Patients achieving DAS-LDA and CLASI-50 at 6 months had a higher probability of remission at 12 months compared with those who did not (
= 0.034 and
= 0.028, respectively).
Belimumab led to clinical improvement in a significant proportion of patients with joint or skin involvement in a real-life setting and was associated with a glucocorticoid-sparing effect. A significant proportion of patients with a partial response at 6 months achieved remission later on during follow-up.
OBJECTIVESThe presented study aimed to explore the presence and the self-identification of depressive symptoms among patients with rheumatic musculoskeletal diseases (RMDs) through the use of the ...Patient Health Questionnaire (PHQ-9).
METHODSBetween June and October 2019, patients from the regional association for people with RMDs in Lombardy, Italy (ALOMAR), were invited to participate in a cross-sectional online survey. Participants completed PHQ-9 along with a survey about their perception of depressive symptoms. Patients were stratified according to PHQ-9 score as followsnot depressed (<4), subclinical or mild depression (5–9), moderate depression (10–14), moderately severe depression (10–14), and severe depression (20–27). Descriptive statistics and analyses of variance were used to explore data.
RESULTSOf the 192 RMD patients who completed PHQ-9, 35 (18.2%) were not depressed, 68 (35.4%) had subclinical or mild depression, 42 (21.9%) had moderate depression, 30 (15.6%) had moderately severe depression, and 17 (8.9%) had severe depression. Contrary to the above findings, only 16 respondents (8.3%) reported that they experienced depressive symptoms, and only 7 of the 16 were being followed by a psychiatrist. Respondents with higher PHQ-9 scores tended to have concomitant fibromyalgia, to be younger, and to be overweight.
CONCLUSIONSThe current results indicate the overall burden of depressive symptoms in RMD patients. While clinical depression (PHQ-9 >10) was detected in 41.2% of respondents, only 8.3% reported that they experience depressive symptoms. Routine screening of RMD patients for depression is therefore critical.
Objective
To investigate predictors of response, remission, low disease activity, damage, and drug discontinuation in patients with systemic lupus erythematosus (SLE) who were treated with belimumab.
...Methods
In this retrospective study of a multicenter cohort of SLE patients who received intravenous belimumab, the proportion of patients who achieved remission, low disease activity, and treatment response according to the SLE Responder Index 4 (SRI‐4) was determined, and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) was used to score disease damage yearly over the follow‐up. Predictors of outcomes were analyzed by multivariate logistic regression with the results expressed as odds ratios (ORs) and 95% confidence intervals (95% CIs).
Results
The study included 466 patients with active SLE from 24 Italian centers, with a median follow‐up period of 18 months (range 1–60 months). An SRI‐4 response was achieved by 49.2%, 61.3%, 69.7%, 69.6%, and 66.7% of patients at 6, 12, 24, 36, and 48 months, respectively. Baseline predictors of response at 6 months included a score of ≥10 on the SLE Disease Activity Index 2000 (SLEDAI‐2K) (OR 3.14 95% CI 2.033–4.860) and a disease duration of ≤2 years (OR 1.94 95% CI 1.078‐3.473). Baseline predictors of response at 12 months included a score of ≥10 on the SLEDAI‐2K (OR 3.48 95% CI 2.004–6.025) and an SDI score of 0 (OR 1.74 95% CI 1.036–2.923). Baseline predictors of response at 24 months included a score of ≥10 on the SLEDAI‐2K (OR 4.25 95% CI 2.018–8.940) and a disease duration of ≤2 years (OR 3.79 95% CI 1.039–13.52). Baseline predictors of response at 36 months included a score of ≥10 on the SLEDAI‐2K (OR 14.59 95% CI 3.54–59.79) and baseline status of current smoker (OR 0.19 95% CI 0.039–0.69). Patients who were in remission for ≥25% of the follow‐up period (44.3%) or who had low disease activity for ≥50% of the follow‐up period (66.1%) accrued significantly less damage (P = 0.046 and P = 0.007). A baseline SDI score of 0 was an independent predictor of achieving low disease activity in ≥50% of the follow‐up period and remission in ≥25% of the follow‐up period. Our findings suggest that the lower the baseline damage, the greater the probability of achieving remission over the course of ≥25% of the follow‐up. Further, there was a negative association between the number of flares reported prior to belimumab initiation and the frequency of belimumab discontinuation due to inefficacy (P = 0.009).
Conclusion
In patients with active SLE and low damage at baseline, treatment with belimumab early in the disease may lead to favorable outcomes in a real‐life setting.
Objective
The research approach on rheumatic musculoskeletal diseases (RMDs) is challenging and patient involvement is an emerging issue to obtain relevant information to research. Despite growing ...interest in non‐pharmacologic aspects of clinical research in RMDs, the patients’ perspectives are currently poorly explored.
Methods
A cross‐sectional no‐profit online survey was devised to identify and rank the priorities for clinical research in RMDs according to patients’ perspectives. Patients were asked to rate the following topics: food/nutrition, air pollution, smoking, work activity, social participation, physical activity, emotional well‐being/stress, alternative medicine, and patient‐physician relationship. The survey was disseminated by ALOMAR (Lombard Association for Rheumatic Diseases) between June and October 2019.
Results
Two hundred RMD patients completed the survey. The topic most rated 188 (94%) was the doctor‐patient relationship, considered very or extremely important. Other topics rated as follows: psychological well‐being 185 (92.5%), physical activity 155 (77.5%), nutrition, eating habits 150 (75%), alternative therapies 144 (72%), work activity 144 (72%), environmental pollution 134 (67%), social life 121 (60.5%) and cigarette smoke 119 (59.5%). The topics considered relevant were perceived to be able to influence disease symptoms. Environmental pollution and smoking were considered the most important for RMD prevention in 43.3% and 48.7% respectively.
Conclusions
This survey highlights the relevance of several unmet needs and indicates that active patient involvement is essential to design successful translational studies and improve clinical outcomes.
Objective
Hip involvement in juvenile idiopathic arthritis (JIA) is one of most important causes of pain and disability. Total hip arthroplasty (THA) is considered the standard when medical ...approaches fail to relieve pain. However, THA is problematic for many reasons. As current literature lacks studies valuating medical management of osteoarthritis (OA) secondary to JIA, we assessed the long-term pain relief effect of US-guided intra-articular viscosupplementation in hip osteoarthritis secondary to JIA versus primary OA under different etiological conditions.
Methods
Patients in both groups received intra-articular Hylan G-F 20 2 ml once a month for 3 consecutive months and every 6 months for 2 years as maintenance. Effectiveness (VAS and WOMAC), NSAID/analgesic consumption, tolerability, withdrawals and reason for discontinuation were collected at each time point. An inverse probability weighting was used to balance the two groups.
Results
We retrospectively retrieved data of 14 JIA patients and 26 primary OA. Weighting successfully accounted for differences between the disease groups supporting the results. Viscosupplementation led to an early and significant improvement of pain and function and concomitant decrease in NSAIDs consumption, while the response diverged over 1 year with loss of benefits in JIA. The worst outcome was observed in active JIA.
Conclusions
Duration of symptom relief after intra-articular injection of hyaluronic acid depends on the nature of arthritis. Multiple courses of viscosupplementation are required to maintain low-dose NSAIDs consumption in patients responsive to treatment while shortening the time between consecutive injections might provide persistent positive results in patients suffering from JIA.
Belimumab was recently approved for treatment of lupus glomerulonephritis (LN).
To evaluate renal response and its predictors in LN patients receiving belimumab in real-life.
We considered all ...patients fulfilling the SLEDAI-2K renal items and/or having estimated glomerular filtration rate (eGFR)≤60 ml/min/1.73 m2, with positive anti-dsDNA and/or low C3/C4 enrolled in the multicentre Italian lupus cohort BeRLiSS (BElimumab in Real LIfe Setting Study), treated with monthly IV Belimumab 10 mg/kg over standard treatment. Primary efficacy renal response (PERR), defined as proteinuria ≤0.7 g/24 h, eGFR≥60 ml/min/1.73 m2 without rescue therapy, was considered as primary outcome. Complete renal response (CRR; proteinuria <0.5 g/24 h, eGFR≥90 ml/min/1.73 m2) was considered as secondary outcome. Prevalence and predictors of PERR were evaluated at 6, 12, 24 months by multivariate logistic regression.
Among the 466 SLE patients of BeRLiSS, 91 fulfilled the inclusion criteria, 79 females, median age 41.0 (33.0–47.0) years, median follow-up 22.0 (12.0–36.0) months. Sixty-four (70.3%) achieved PERR, of whom 38.4% reached CRR. Among patients achieving PERR at 6 months, 86.7% maintained response throughout the follow-up. At multivariable analysis, hypertension (OR 95%CI: 0.28 0.09–0.89, p = 0.032), high baseline serum creatinine (0.97 0.95–0.99, p = 0.01) and high baseline proteinuria (0.37, 0.19–0.74, p = 0.005) negatively predicted PERR. Positive predictors of PERR at 12 and 24 months were baseline anti-Sm positivity (OR 95%CI: 6.2 1.21–31.7, p = 0.029; 19.8 2.01–186.7, p = 0.009, respectively) and having achieved PERR at 6 months (14.4 3.28–63.6; 11.7 2.7–48.7, p = 0.001 for both).
Add-on therapy with belimumab led to durable renal response in patients with LN in a real-life setting.
•Belimumab is effective and safe as add-on therapy in LN in real-life.•Higher baseline proteinuria hampers response and favors belimumab discontinuation.•Early achievement of renal response upon belimumab heralds response durability.
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