Kinetics of response to iloprost evaluated by laser speckle contrast analysis in systemic sclerosis.

OBJECTIVE: Iloprost (ILO) is recommended for the treatment of systemic sclerosis (SSc) microangiopathy, but there is no common consensus on its optimal dosage. The aim of this study is to evaluate the kinetics of response to ILO administered in a daily outpatient scheme in SSc subjects using laser speckle contrast analysis (LASCA). METHOD: Adult SSc patients in stable therapy with ILO administered for 6 h for 2 consecutive days every 4 weeks were enrolled. Peripheral finger perfusion was assessed by LASCA. Each patient underwent five LASCA evaluations: before and after each day of ILO (D1pre, D1post, D2pre, and D2post) and after 4 weeks (D30). RESULTS: Twenty-seven SSc patients (77.8% female, mean age 61.5 years) were enrolled. LASCA showed an increase in perfusion at the end of each ILO course, but on the second day (both D1pre vs D2pre and D2pre vs D2post) the increase was no longer significant in half of the fingers. Moreover, compared to D1post, at the beginning of the second ILO day most of the fingers had already shown a significant reduction in perfusion. After 1 month, there were no statistically significant differences between the perfusion values of D1pre and D30. CONCLUSION: This LASCA study highlights the transience of the vasoactive effect of ILO, with a perfusion benefit that is completely lost after 1 month. The brevity of the perfusion effect of ILO and the use of LASCA are elements to consider in the design of future SSc trials to determine the optimal ILO dosage.

Evaluation of risk factors and biomarkers related to arterial and venous thrombotic events in idiopathic inflammatory myopathies.

Objectives: This study aimed to assess the contribution of traditional/disease-related risk factors and biomarkers linked to arterial and venous thrombotic events (TEs) in patients with idiopathic inflammatory myopathies (IIMs).Method: The occurrence of arterial and/or venous TEs at the time of or after IIM diagnosis was retrospectively evaluated in a cohort of 253 patients with IIMs, resulting in a final population of 246 IIM patients, 51 with reported TE (cases) and 195 without a history of TE (comparators). Information on disease characteristics and traditional risk factors for arterial and venous TE (essential hypertension, diabetes, dyslipidaemia, smoking, malignancy) was retrieved. Serum levels of anti-phospholipid antibodies (aPLs) and adhesion molecules were analysed at the time of IIM diagnosis and at the time of the TE in cases.Results: One in five IIM patients (21%) had experienced a TE, arterial TE in 22 and venous TE in 29 patients, with a peak prevalence within 5 years after diagnosis. Among traditional/disease-related risk factors, only older age was associated with both arterial and venous TEs, after adjusting for other covariates. Low serum levels of e-selectin were associated with higher odds of developing a TE, without specific association with either arterial or venous TEs. Only 6% of IIM patients had aPLs, with no significant difference between cases and comparators.Conclusions: An increased risk of both venous and arterial TEs should be considered in IIM patients, particularly close to diagnosis and in elderly people. Low serum levels of e-selectin may predict TE in IIM patients, but the underlying biological mechanism is not known.

Prostanoids in scleroderma microangiopathy: clinical and pharmacoeconomic comparison between two intravenous regimens.

Objectives: Intravenous iloprost (ILO) has widely demonstrated its effectiveness and safety in systemic sclerosis (SSc) patients. Unfortunately, there is no clear consent about dosage, duration, frequency, and infusion modality. The aim of this study was to compare two different therapeutic schemes in the same cohort of consecutive SSc subjects, evaluating differences in terms of effectiveness [digital ulcer (DU) outcome], safety, and direct healthcare costs.Method: This was a retrospective observational study of 47 patients classified with SSc treated with intravenous ILO for severe Raynaud's phenomenon and/or DUs. Two regimens were compared: a continuous inpatient scheme and a daily outpatient scheme. Demographics and clinical data, concomitant therapies, adverse events, and data on resource use and costs were collected.Results: The number of DUs rose slightly with the switch from the continuous to the daily scheme (0.61 ± 1.2 vs 1.1 ± 1.7). Moreover, in the daily scheme there was an increase in the number of therapeutic cycles (2.4 ± 0.7 vs 4.71 ± 1.4, p < 0.001) and an increase in patients treated with other vasoactive drugs. There was a reduction in ILO tolerability and more than half of the patients suspended the treatment. Five patients required hospitalization for severe and refractory DUs in the daily scheme. Moreover, the costs of the two treatments were comparable [median 7174 (range 2748-18 524) EUR vs 6284 (3232-22 706) EUR, p = 0.712].Conclusion: Treatment with a daily scheme of ILO is characterized by worse tolerability and a higher dropout rate compared to a low-flow regimen, with similar costs. We suggest that a low-flow continuous therapeutic scheme is preferable in SSc patients.

Histopathology of the muscle in rheumatic diseases.

The presence of muscular symptoms is common in rheumatological clinical practice, but often the differential diagnosis between muscular involvement in connective tissue diseases, vasculitis and drug-induced myopathy may be difficult. In addition to clinical assessment, laboratory analysis and instrumental examinations, muscle biopsy may help to clarify the diagnosis in patients with muscular involvement. The purpose of this review is to provide a critical analysis of the current medical literature on muscular histopathology, to help clinicians to identify when to perform muscular biopsy and to provide a practical guide to a better understanding of the pathology report. Moreover, we provide an overview of the muscular involvement and the most common histopathological findings in rheumatic diseases.

The use of rituximab in idiopathic inflammatory myopathies: description of a monocentric cohort and review of the literature.

Rituximab (RTX), a chimeric monoclonal antibody targeted against CD20, has been used to treat refractory inflammatory myopathies (IIM). The primary objective of this study was to retrospectively assess the efficacy of RTX in reducing disease activity in patients with IIM refractory to conventional therapy. Secondary aim was the evaluation of adverse events (AE) during the treatment period. We examined 26 patients with a diagnosis of IIM, referred to our Rheumatology Unit and treated with RTX for active refractory disease. Patients were treated with RTX 1000 mg i.v., twice, with a 2-week interval. RTX treatment was associated with a significant reduction of creatine kinase (p=0.001) after six months compared to the baseline, an improved muscular strength measured with MMT8 (p<0.001) and a reduction of the extramuscular activity of the disease measured with MYOACT (p<0.001). In particular, RTX improved DM skin rash, arthritis and pulmonary manifestations. Autoantibody positivity (in particular antisynthetase, anti- SRP and antiRo/SSA), and a disease duration <36 months at the moment of the treatment are associated with a better response rate. Treatment with RTX was also associated with a reduction of the mean daily dose of steroids needed to control disease activity (p=0.002). Our results have confirmed that RTX is efficacious in the treatment of refractory IIM. Ad hoc controlled trials are needed to better clarify the specific subset of patients who may better respond to the treatment and the optimal therapeutic schedule.

Post-occlusive reactive hyperaemia (POHR) in systemic sclerosis: very early disease (VEDOSS) represents a separate entity compared to established disease.

OBJECTIVES: Vascular involvement is a key feature of systemic sclerosis (SSc). Vascular changes are central to the pathogenesis of the disease and the assessment of vascular involvement has a prognostic value. This assessment therefore has a pivotal role in the management of SSc patients. The aim of our study was to evaluate post-occlusive reactive hyperaemia (PORH) in consecutive SSc patients and to test whether a PORH test might be a useful tool for the early diagnosis of SSc. METHOD: Between April 2011 and April 2015, 60 consecutive SSc patients (mean age 56 ± 15 years, females:males = 18:1) were enrolled in the study. The patients were divided into those with full-blown SSc (n = 50) and those with very early diagnosis of SSc (VEDOSS) (n = 10) according to the literature. Laser speckle contrast analysis (LASCA) was used to assess PORH. RESULTS: A statistically significant difference was detected in the post-ischaemic hyperaemic peak flow between VEDOSS and established SSc (424% vs. 137%, p = 0.0011). PORH peak flow decreased according to the capillaroscopic pattern (early = 419%, active = 163%, late = 145%, p = 0.0027). Moreover, a correlation between capillary density and peak flow was revealed (rho = 0.33, p < 0.01). CONCLUSIONS: These data show a different pattern of vascular involvement in VEDOSS compared to established disease that mirrors capillaroscopic changes. Functional features of very early and established disease seem to be the physiological counterpart of abnormalities detected by capillaroscopy. The POHR test might be a useful aid for further characterization of vascular involvement in SSc. In particular, blunted POHR might prove a tool to separate pre-clinical from full-blown SSc.

Real-Time PCR and Droplet Digital PCR: two techniques for detection of the JAK2(V617F) mutation in Philadelphia-negative chronic myeloproliferative neoplasms.

INTRODUCTION: Philadelphia-negative chronic myeloproliferative neoplasms (MPNs) are clonal disorders that present JAK2(V617F) mutation in 50-95% of cases. The main objective of this study was the comparison of two PCR methods, real-time (qPCR) and droplet digital PCR (DD-PCR) for detection of the JAK2(V617F) mutation, to assess analytic sensitivity, specificity, and feasibility of the two methods. METHODS: Ninety-nine patients with MPN of 225 presenting the JAK2(V617F) mutation by qPCR have been evaluated by DD-PCR also. RESULTS: We demonstrated an absolute concordance in terms of specificity between the two methods, DD-PCR showing a higher sensitivity (half a log higher than qPCR). As expected, a progressive increase of mutant allele burden was observed from essential thrombocythemia (ET) to polycythemia vera (PV) and primary myelofibrosis (PMF) to secondary myelofibrosis (SMF). CONCLUSION: In conclusion, our study showed that DD-PCR could represent a new and promising technological evolution for detection of JAK2 mutation in MPNs.

Systemic sclerosis: a critical digest of the recent literature.

Systemic sclerosis is a complex disease characterised by chronic multisystem involvement of internal organs; every year many studies are published on the diagnosis, pathogenesis and treatment of the disease. In this article, we provide a critical analysis of the recent literature on systemic sclerosis, with particular focus on the most relevant studies published over the last two years.

Otologic symptoms in temporomandibular disorders patients: is there evidence of an association-relationship?

Several studies in the literature investigated the association between temporomandibular disorders (TMD) and otogenous symptoms, like vertigo, tinnitus, otalgia and muffling, although the question of the existence of a cause-effect relationship is still controversial. Epidemiological findings showed that the prevalence of ear symptomatology in the general population is variable from 10% to 31%, and increases up to 85% in TMD patients. Based on these data, many attempts have been performed to describe the physiopathological interactions between aural symptoms and TMD, as a strict anatomical link exists between the structures of the ear and those of the stomatognathic system. Unfortunately, methodological weaknesses of most studies are evident so that the comparison of results is often difficult. Considering these premises, the present study critically reviewed the literature on this debated issue, discussing the main etiopathogenetic hypotheses, the features of ear symptomatology in TMD patients and its relationship with TMD treatment in order to present current suggestions about the relationship between aural and TMD symptoms. Suggestions for future researches have been also presented, since a full understanding of this plausible interaction will be an important factor in diagnosis making and treatment planning for both pathologies.

Clear experimental evidence for p-wave attachment-threshold behavior in electron attachment to chlorine molecules.

Using the laser photoelectron attachment method and chlorine molecules in a seeded supersonic beam, we have measured the energy dependence of the cross section for dissociative electron attachment (DA; Cl- formation) over the range 0-195 meV with an energy width of about 1 meV. Our data provide the first clear experimental evidence for p-wave behavior of a DA cross section near zero energy and are in good overall agreement with recent theoretical predictions.