OBJECTIVE:To assess the feasibility of a new device for telemonitoring vital parameters during iloprost infusion.MATERIALS AND METHODS:In a pilot study, patients with systemic sclerosis received iloprost infusion while being telemonitored with Umana T1 Heart Monitor, within the hospital, under the supervision of family/community nurses and rheumatologists. Patients were administered a questionnaire to obtain information on satisfaction, practicability, and compliance with the new monitoring device.RESULTS:Data recorded by the device for blood pressure, heart rate, and oximetry were concordant with those registered directly by nurses. Most patients found the device useful and thought it could be used at home, even while working.CONCLUSIONS:Umana Heart Monitor T1 could be a valuable aid in at-home iloprost therapy in patients with systemic sclerosis.

Background Interstitial lung disease (ILD) is a common manifestation of systemic sclerosis and other Rheumatic Diseases, and is one of the major causes of mortality. Nintedanib, a tyrosine kinase inhibitor, has been shown to have antifibrotic and anti-inflammatory effects in preclinical models of systemic sclerosis and ILD. Objectives To evaluate efficacy and safety of Nintedanib in pulmonary fibrosis secondary to Connective Tissue Disease. Methods Ten patients with pulmonary fibrosis secondary to Connective Tissue Disease treated with Nintedanib were monitored at baseline, 6 and/or 12 months, with clinical assessment, chest CT scan and/or pulmonary function testing (PFT) with assessment of the diffusing capacity for CO (DLCO). 8/10 patients had a diagnosis of Progressive Systemic Sclerosis, while the remaining ones had Polydermatomyositis and Mixed Connectivitis. All patients were dyspnoic at baseline and presented with dry cough. All patients had pulmonary fibrosis according to high-resolution chest CT scan. All patients had been treated with at least one csDMARD or bDMARD (cyclophosphamide, azathioprine, cyclosporine, rituximab, tocilizumab), prior to receiving nintedanib. At baseline 2/10 patients were treated with Nintedanib monotherapy, 7/10 were in combination therapy with Mycophenolate, 1 patient received a combination therapy with cyclosporine. Results Compared to baseline values, 4/7 patients showed stationarity of the respiratory function parameters (DLCO), in 2/7 patients it was observed a significant improvement of the DLCO (with a change of 15%) while in only 1 patient there was a worsening over time. FVC remained stable over time except in 1 patient who got a significant improvement. In 5/9 patients cough improved (unchanged in the rest of patients). Dyspnea (NYHA scale) improved in 6/9 patients, remained stationary in 2/6 patients and became worse in 1 patient. 8/9 patients had a stable chest CT at 6 and / or 12 months, while only 1 patient witnessed a further worsening of the fibrosis. 50% of the patients showed good gastrointestinal tolerance to the full dose of nintedaninb. The other half had the dose reduced in order to improve gastrointestinal symptoms. Conclusion Our data show that patients with ILD associated with Rheumatic Diseases treated with nintedanib had a clinical benefit over dyspnea and cough symptoms and a stabilization of radiological findings 12 months after starting the treatment. Also, respiratory function parameters remained stable over time. Gastrointestinal adverse events, including diarrhea, were common in these patients, but therapeutic dose adjustment led to fast symptoms resolution and good tolerance. References [1]Kristin B Highland, Oliver Distler, Masataka Kuwana, Yannick Allanore, Shervin Assassi, Arata Azuma, Arnaud Bourdin, Christopher P Denton, Jörg H W Distler, Anna Maria Hoffmann-Vold, Dinesh Khanna, Maureen D Mayes, Ganesh Raghu, Madelon C Vonk, Martina Gahlemann, Emmanuelle Clerisme-Beaty, Mannaig Girard, Susanne Stowasser, Donald Zoz, Toby M Maher, SENSCIS trial investigators. Efficacy and safety of nintedanib in patients with systemic sclerosis-associated interstitial lung disease treated with mycophenolate: a subgroup analysis of the SENSCIS trial. Lancet Respir Med. 2021 Jan;9(1):96-106. [2]Oliver Distler, Kristin B Highland, Martina Gahlemann, Arata Azuma, Aryeh Fischer, Maureen D Mayes, Ganesh Raghu, Wiebke Sauter, Mannaig Girard, Margarida Alves, Emmanuelle Clerisme-Beaty, Susanne Stowasser, Kay Tetzlaff, Masataka Kuwana, Toby M Maher, SENSCIS Trial Investigators. Nintedanib for Systemic Sclerosis-Associated Interstitial Lung Disease. N Engl J Med. 2019 Jun 27;380(26):2518-2528. Disclosure of Interests None declared

Objective: To compare Routine Assessment of Patient Index Data 3 (RAPID3) on a Multidimensional Health Assessment Questionnaire (MDHAQ) with the Western Ontario and Mc-Master Universities Osteoarthritis Index (WOMAC) in patients with knee osteoarthritis and to evaluate its reliability. Methods: Consecutive patients with symptomatic knee osteoarthritis (VAS >50 mm) based on ACR Classification criteria were enrolled. A radiological Kellgren-Lawrence index 1–2 was required. Correlation between indices was estimated with Spearman's Rho. A General Linear Model (GLM) was used to estimate the effect size between indices. Reliability analysis was assessed finally using coefficients of IntraClass Correlation. Results: 221 patients were enrolled and completed WOMAC and MDHAQ-RAPID3 questionnaires during the period 2009–2013. RAPID 3 mean value was 5.7 ± 1.3 in patients with knee OA. Kurtosis −0.287 ± 0.211, skewness −0.61 ± 0.12. The ceiling/floor effect, % of responses that are coded at the maximum/minimum value, ranged <10%. WOMAC total score was 57.2 ± 13.4. Spearman's rho index was 0.84. Using a General Linear Model (GLM) to estimate the proportion of variation of WOMAC explained by RAPID 3 we found an effect size of 0.82 (p < 0.01). Coefficients of IntraClass Correlation between mean values of WOMAC and RAPID3 was 0.812, F test with P = 0.001. Conclusion: RAPID3 scores provide similar quantitative information to WOMAC in patients with knee osteoarthritis.

Osteoporosis is a major health concern that is associated with an increased risk of first and subsequent bone fractures. Untreated osteoporosis results in considerable morbidity. Currently, bisphosphonates are the mainstay of treatment for osteoporosis and the aim of this study was to assess the effects of intravenous (IV) and intramuscular (IM) neridronate (NE) on femoral/lumbar bone mineral density (BMD) and to fracture the risk in patients with postmenopausal osteoporosis. Data were collected on age, weight, body mass index, physical activity, smoking, height loss, history of falls, total hip and lumbar BMD, and creatinine clearance. Inclusion criteria were a lumbar or femoral BMD T score < 2.5; Exclusion criteria were secondary osteoporosis, previous osteoporotic fracture, prior bisphosphonates or osteoporosis medications other than calcium or colecalciferol, presence of any concomitant skeletal metabolic disease. METHODS: 164 patients (mean age 64±2.7 years) with postmenopausal osteoporosis confirmed with a lumbar and femoral DEXA BMD scan received NE IV 100mg every 8 weeks for 18 months and subsequently IM NE 25 mg every 4 weeks for 18 months. All patients had gastric or esophageal conditions that contraindicated treatment with oral bisphosphonates (BPs). All subjects received daily calcium 1 g and vitamin D 800 UI. Lumbar and femoral DEXA BMD scans were performed at baseline, 18 months and 36 months. RESULTS: After 18 months of IV therapy mean ±SD lumbar BMD was significantly increased (baseline -2.8±1.2 vs 18 months -2.6±1.4; p<0.01). Mean ±SD femoral neck BMD was also improved (baseline -2.15±1.1 vs 18 months -2.01±0.5; p<0.05). After an additional 18 months of IM NE the mean ±SD BMD values were lumbar -1.89±0.8 and femur -1.49±1.48; p< 0.01 vs. baseline. CONCLUSION: The results of this study confirm the role of NE in the treatment of postmenopausal osteoporosis and indicate the potential usefulness of intramuscular administration in the treatment of these patients. *Rheumatology Unit Fornaroli Hospital Magenta 20013 Italy Correspondence to Alfredomaria Lurati (e-mail: alfredomaria.lurati@pec.it).

Background RAPID3 (routine assessment of patient index data) is an arithmetic composite index of three Core Data Set, patient self-report, measures: physical function (0-3 converted to 0-10), pain (0-10), and patient global estimate (0-10) for a total of 0-30. It can be completed in the waiting room and can be calculated in only few seconds. Objectives Aim of this study was to compare RAPID3 with the Western Ontario and Mc-Master Universities Osteoarthritis Index (WOMAC) in patients with knee or hip osteoarthritis (OA) Methods patients with symptomatic knee or hip osteoarthritis as main rheumatologic diagnosis (VAS pain > 50 on a visual scale 0-100mm) according to the ACR (American College of Rheumatology) criteria and with stage 2 or 3 according to the Kellgren-Lawrence radiographic criteria were eligible. All subjects were clinically evaluated individually by an experienced rheumatologist and were asked to complete the self-report questionnaires (the original version of the WOMAC for hip or knee osteoarthritis and the RAPID3). There was no specific order in which the tests were completed; rather, each participant selected the order. Agreement between WOMAC and RAPID3 scores was estimated with rho Spearman correlation statistic. Cronbach’s alpha also was determined to evaluate the internal consistency of RAPID3 items Results 218 patients (63 males, 155 females) with hip (n=93) or knee (n=125) osteoarthritis were enrolled in daily practice clinical care during 2010-2012. Mean age (±SD) was 62±7.4 years old. Mean score was 58±8.1 for WOMAC and 7.2±1.5 for RAPID3. RAPID3 and WOMAC have shown a global correlation rho index of 0.78 (p 0.05). The Spearman’s rho was 0.78 for hip osteoarthritis (p Conclusions Up to date there’s not literature about the use of RAPID3 in patients with OA. In our study we found a strong correlation between RAPID3 and WOMAC in patients with either hip and knee OA. RAPID3 provide informative quantitative data for patient status from one visit to the next comparable to other self-reported questionnaire as WOMAC in a time sparing manner Disclosure of Interest None Declared

Lurati A, Bertani L, Marrazza M, Re KA, Bompane D, Scarpellini M. Biologics: Targets and Therapy. 2012;6:83–87.On page 87, the disclosure was listed as ‘The authors report no conflicts of interest in this work.’ in error. The correct disclosure should be ‘An unrestricted publication grant was provided by Roche S.p.A. The authors have no other conflicts of interest to report.’Read the original article

Objectives To report side effects seen in a clinical cohort of patients >65 years old with Rheumatoid Arthritis treated with Etanercept and to compare the SEs rate with patients ≤ 65 years old. Methods All patients with RA that started Etanercept from November 2005 to November 2006 and referring to our Rheumatology Unit until November 2011 were included in this study and prospectively followed to collect side effects related to therapy (Group A patients ≤ 65 years old, group B > 65 years old). All SEs observed during 5 years, primarily infective adverse event (IAE) and Serious adverse event (SAE), were collected. Data were analyzed with Mantel Cox survival analysis Results Eighty two patients were enrolled in this study from November 2005 to November 2006 and followed until November 2011: 31 (28 females, 3 males) aged ≤ 65 years (Group A), 52 (40 females, 11 males) aged > 65 years (Group B). In the patients > 65 years old the safety profile of Etanercept was similar than in patients ≤ 65 years old (p>0.05) and the survival curves between the groups were similar (p>0.05). Rates of infection were comparable across the groups (p>0.05). Urinary tract infections and upper respiratory tract infections (including nasopharyngitis) were the most frequently reported IAEs. Also rates of SAEs were comparable in the two groups (p>0.05) (Tab. 1) Mean survival time before that a first AE related to therapy with Etanercept was recorded was 29.6 months ±2.42 in the Group A, 31.3± 2.6 in the Group B. Median survival time was 31.7 months in the Group A and 34.4 in the Group B, (p>0.05). No significant correlation has been found between the survival time until the first adverse event and the age (p=0.63). Mean survival time before definitive therapy suspension with Etanercept due to SAEs was 46.2 months ±2.99 in the ≤ 65 years old group and 47.7± 4.1 in the elderly group (p>0.05). No significant correlation has been found between therapy duration when SAE occurred and the age used as a covariate in the Mantel Cox equation (p=0.728). Finally, a retention rate of 64.7 % at 5 years in the group <65 years old and 63.0 % in the ≥ 65 years old group was observed Conclusions In our experience, anti-TNFα agent Etanercept has been safe in elderly patients; the risk of SEs (primarily IAE and SAE) in these patients was no greater than in subjects aged ≤ 65 years. However, such inhibitors are associated with various and numerous SEs, elderly patients with RA should be carefully monitored. Disclosure of Interest None Declared

Background There is increasing evidence for the use of intra-articular hyaluronic acid in the treatment of hip osteoarthritis (OA) using ultrasound-guided injections. More over, two-dimensional and more recently 3D ultrasonography is useful in detecting articular abnormalities in osteoarthritis. Objectives Primary objective of our study was to assess the efficacy in pain relieving of ultrasound guided hip injections in patients with hip osteoarthritis. Secondary objective was to establish a correlation between a global score of structural damage based on 2D and 3D ultrasound images and response to treatment. Methods patients with hip OA according to ACR criteria, grade 1 to 3 according to Kellgren and Lawrence were considerate eligible. Esaote Mylab 25 with 3D BL433 5-12 MHz probe was used. All subjects enrolled were treated with a course of three intra-articular jaluronic acid injections (800.000-1170000 dalton m.w.) 1 week apart and were followed every 3 months for a 6-months period after the last injection. The injections were performed under US guidance with an antero-superior approach according to the Magenta School’s method. Treatment efficacy was assessed through visual analogue scale (VAS) pain quantification (at baseline, at last injection and after 3 and 6 month). Additionally, 2D (longitudinal and transverse views) and 3D (longitudinal, transverse and coronal views) ultrasound images were collected and scored according to Qvistgaard method based on 4 items (osteophyte score 0-3, femoral head score 0-3, fluid score 0-2 and synovial profile score 0-2) and also through a global score derived from the sum of single item score. Results Eleven patients (8 females and 3 males; age 47-83 years) were enrolled in this study. At 6 months after the injections course we observed a reduction in the pain VAS versus baseline mean values from 76.4 to 33.5 (p<0.05). Global Qvistgaard score was 4.2±0.8 and 5.1±0.2 (mean ± SD) using 2D and 3D views respectively. The VAS scores at baseline, 3 months and 6 months were significantly related to Qvistgaard scores (r =0.33 for 2D score and 0.64 for 3Dscore respectively, p<0.05). A linear regression model confirmed the role of radiological score as predictive of clinical response in terms of VAS Conclusions our data confirm the efficacy of intra-articular medium m.w. hyaluronic acid in the treatment of hip OA, with a clinical improvement in pain for at least 6 months post injections course. Furthermore, our study suggests a correlation between echographic findings and clinical response, especially using 3D views. References Qvistgaard E et al.Intra-articular treatment of hip OA: a randomized trial of hyaluronic acid, corticosteroid, and isotonic saline. Osteoarthritis Cartilage 2006;14(2):163-70 Disclosure of Interest None Declared

In clinical practice it is possible to find patients with clinical signs suggestive of anti-phospholipid syndrome (APS) who are persistently negative for the routinely used anti-phospholipid antibodies (aPL). Therefore, the term proposed for these cases was seronegative APS (SN-APS). We investigated the clinical usefulness of thin-layer chromatography (TLC) immunostaining in detecting serum aPL in patients presenting clinical features of SN-APS. Sera from 36 patients with SN-APS, 19 patients with APS, 18 patients with systemic lupus erythematosus (SLE), 20 anti-hepatitis C virus (HCV)-positive subjects and 32 healthy controls were examined for aPL using TLC immunostaining. Anti-beta 2-glycoprotein-I, anti-annexin II, anti-annexin V and anti-prothrombin antibodies were tested by enzyme-linked immunosorbent assays (ELISA). Eahy926, a human-derived endothelial cell line, was incubated with immunoglobulin (Ig)G fraction from SN-APS patients and analysis of phospho-interleukin (IL)-1 receptor-associated kinase (IRAK) and phospho-nuclear factor (NF)-B was performed by Western blot, vascular cell adhesion molecule 1 (VCAM-1) expression by cytofluorimetric analysis and supernatants tissue factor (TF) levels by ELISA. TLC immunostaining showed aPL in 58.3% of SN-APS patients: anti-cardiolipin in 47.2%, anti-lyso(bis)phosphatidic acid in 41.7% and anti-phosphatidylethanolamine in 30.5%. Six of 36 patients showed anti-annexin II. Incubation of Eahy926 cells with IgG from SN-APS induced IRAK phosphorylation, NF-B activation, VCAM-1 surface expression and TF cell release. TLC immunostaining could identify the presence of aPL in patients with SN-APS. Moreover, the results suggest the proinflammatory and procoagulant effects in vitro of these antibodies.

Purpose: The relationship between antiCD20 therapy with rituximab and the lymphocytes phenotype in patients with rheumatoid arthritis was investigated, with an attempt to establish a relationship between commonly used clinical activity indices and variations in leukocyte count, in particular natural killer (NK) lymphocytes.Methods: Patients with seropositive (cyclic citrullinated peptides and rheumatoid factor -positive) rheumatoid arthritis (according to the American College of Rheumatology 1987 criteria) refractory to conventional and antitumor necrosis factor-alpha agents who were subsequently treated with rituximab, a chimeric monoclonal antibody directed against CD20, were enrolled between January 2009 and September 2009. All subjects were treated with rituximab standard rheumatologic dose of 1.0 g on days 1 and 15 every 6 months for at least 2 years. A clinical evaluation was performed at baseline and subsequently every 3 months thereafter. At each assessment activated NK (CD56+/CD16+/CD54bright) cell count was collected and disease activity was assessed using Disease Activity Score in 28 Joints and the Simplified Disease Activity Index (SDAI).Results: Thirty-four patients were enrolled (mean age +/- standard deviation: 54.8 +/- 12.8 years). Basal SDAI was 21.75 +/- 5.4 and NK cell count mean value was 157.6 +/- 90. After 24 months, SDAI was 14 +/- 1.2 and NK cell count mean value was 301.7 +/- 21 (P, 0.05). An inverted correlation between SDAI and NK count was observed at 3 months (r =-0.36, P, 0.05), 6 months (r =-0.48, P, 0.45), 9 months (r =-0.47, P, 0.05), 12 months (r =-0.41, P, 0.01), 15 months (r =-0.58, P, 0.05), 18 months (r =-0.53, P, 0.05), 21 months (r =-0.68, P, 0.05), and 24 months (r =-0.61, P, 0.05). A linear regression model between all variables collected and SDAI/Disease Activity Score in 28 Joints at 6 months and 12 months confirmed a significant relationship between SDAI/Disease Activity Score in 28 Joints and NK cell count.Conclusion: The data confirm the clinical efficacy of rituximab and suggests the use of NK cells as a predictor of clinical response in patients with rheumatoid arthritis.

Autoimmune diseases ( AD) occur frequently in women during their childbearing years and may influence pregnancy outcome and neonatal health. Patients with systemic lupus erythematosus (SLE) can experience a disease flare-up during pregnancy with potential negative effects on the product of conceptus, especially if the disease is active. Recurrent pregnancy loss is now considered as a treatable clinical condition associated with the presence of circulating antiphospholipid antibodies (aPL). The neonatal lupus syndromes (NLS), caused by the transplacental passage of maternal IgG anti-Ro/SS-A and anti-La/SS-B antibodies to the fetus, carry significant morbidity and mortality in case of cardiac manifestations. Immunosuppressive agents are often administered during pregnancy in order to control maternal disease and to ensure a better pregnancy outcome. Nowadays, owing to our increasing knowledge of the disease pathophysiological mechanisms and the development of combined medical-obstetric clinics, pregnancy outcome in patients with AD has notably improved.

Systemic lupus erythematosus is a protean disease which may present manifestations that resemble other diseases posing serious problems of differential diagnosis. Visceral leishmaniasis is a parasitic infection, endemic in 88 countries, whose hallmarks may mimic a lupus flare. Fever, pancytopenia, splenomegaly, hypergammaglobulinemia, production of autoantibodies and complement consumption are some of the overlapping features between the two diseases. Thus, extra attention must be paid to patients with lupus who present with the mentioned symptoms. Diagnosis of visceral leishmaniasis relies on the detection of leishmania antibodies, on the presence of amastigotes in bone marrow aspirates, biopsies and cultures of the parasite. Treatment is based on the use of i.v. liposomal amphotericin B. The missed recognition of a leishmania infection in a lupus patient may lead to death, since both the omission of a specific anti-parasite treatment and the increase of the immunosuppressive therapy, in the conviction of a lupus flare, accelerate a fatal outcome. In this paper we present a case of visceral leishmaniasis occurring in a lupus patient. The clinical and laboratory features that overlap in the two diseases and the current literature on the topic were discussed.

The pathogenesis of Rheumatoid Arthritis (RA) is still largely unknown. From the seminal experimental studies, suggesting a multifactorial mechanism leaded by an antigen specific activation, the direct role of innate immunity in the disease progression has been recently emphasized. In the natural history of RA, characterized by the three phases of the induction, maintenance and tissue destruction, innate immunity seems to be the central player. On the other hands the recent advances about the molecules involved in the T lymphocyte activation, the T cell role in the mechanism of erosion, and the studies about chemochines in the homing and angiogenesis processes support the theory of an antigen specific activation of the adaptive immune system. Therefore, during RA, the pathogenesis of sinovitis and erosions comes from independent pathways involving either innate and adaptive immunity resulting in the final induction of the articular damage.