Speckle-tracking global longitudinal strain predicts death and cardiovascular events in patients with systemic sclerosis.

Aims: Albeit often asymptomatic, heart involvement in systemic sclerosis (SSc) represents a negative prognostic factor, accounting for nearly one-fourth of all deaths. Global longitudinal strain (GLS) is accurate in detecting heart involvement in patients with SSc and no overt cardiac disease and allows early detection and longitudinal monitoring, but its association with clinical endpoints has not been tested so far. The primary outcome was the association between left and right GLS and mortality for all causes. The secondary outcome was the association between left and right GLS and hospitalizations. Methods and results: A prospective longitudinal study enrolling all consecutive patients with SSc without structural heart disease or previous cardiovascular event.A total of 164 patients were enrolled, of whom 19 (11.5%) died during follow-up and 48 (29.3%) were hospitalized. Both left (LV) and right ventricle (RV) GLS at enrolment were independently associated with an increased risk of death for all causes and hospitalizations. Patients with biventricular GLS impairment, respectively, had a 4.2-, 4.9-, and 13.9-fold increased risk of death when compared with patients with only LV, only RV, or no impairment (P < 0.001). The incidence of hospitalization in patients with biventricular GLS impairment was nearly four times higher when compared with patients with only LV or only RV impairment, and nine times higher when compared with normal biventricular GLS (P < 0.001). Conclusion: Biventricular GLS is associated with an increased risk of death and hospitalization in patients with SSc during a median of 3-year follow-up, acting as a reliable and accurate prognostic tool in everyday practice.

Adeno-Associated Virus Type 5 Infection via PDGFRα Is Associated With Interstitial Lung Disease in Systemic Sclerosis and Generates Composite Peptides and Epitopes Recognized by the Agonistic Immunoglobulins Present in Patients With Systemic Sclerosis.

OBJECTIVE: The etiopathogenesis of systemic sclerosis (SSc) is unknown. Platelet-derived growth factor receptors (PDGFRs) are overexpressed in patients with SSc. Because PDGFRα is targeted by the adeno-associated virus type 5 (AAV5), we investigated whether AAV5 forms a complex with PDGFRα exposing epitopes that may induce the immune responses to the virus-PDGFRα complex. METHODS: The binding of monomeric human PDGFRα to the AAV5 capsid was analyzed by in silico molecular docking, surface plasmon resonance (SPR), and genome editing of the PDGFRα locus. AAV5 was detected in SSc lungs by in situ hybridization, immunohistochemistry, confocal microscopy, and molecular analysis of bronchoalveolar lavage (BAL) fluid. Immune responses to AAV5 and PDGFRα were evaluated by SPR using SSc monoclonal anti-PDGFRα antibodies and immunoaffinity-purified anti-PDGFRα antibodies from sera of patients with SSc. RESULTS: AAV5 was detected in the BAL fluid of 41 of 66 patients with SSc with interstitial lung disease (62.1%) and in 17 of 66 controls (25.75%) (P < 0.001). In SSc lungs, AAV5 localized in type II pneumocytes and in interstitial cells. A molecular complex formed of spatially contiguous epitopes of the AAV5 capsid and of PDGFRα was identified and characterized. In silico molecular docking analysis and binding to the agonistic anti-PDGFRα antibodies identified spatially contiguous epitopes derived from PDGFRα and AAV5 that interacted with SSc agonistic antibodies to PDGFRα. These peptides were also able to bind total IgG isolated from patients with SSc, not from healthy controls. CONCLUSION: These data link AVV5 with the immune reactivity to endogenous antigens in SSc and provide a novel element in the pathogenesis of SSc.

Upadacitinib effectiveness and factors associated with minimal disease activity achievement in patients with psoriatic arthritis: preliminary data of a real-life multicenter study.

BACKGROUND: Upadacitinib (UPA) is a selective JAK inhibitor recently approved for the treatment of psoriatic arthritis (PsA). In this post-approval study, we aimed to evaluate the effectiveness and safety of UPA over 24 weeks and identify clinical predictors of response, in a multicentric cohort of patients affected by PsA. METHODS: One hundred and twenty-six patients with PsA treated with UPA were enrolled in 10 Italian centres. UPA effectiveness outcomes, such as the proportion of patients with MDA status, DAPSA remission, and low disease activity, ASDAS-CRP inactive and low disease activity, and change from baseline in DAPSA and ASDAS-CRP scores, were evaluated every 12 weeks until week 24. The proportion of DAPSA minor, moderate, and major improvement, and ASDAS clinically important improvement (CII) and major improvement (MI) were considered as well. All treatment-related adverse events were collected during the observation period. Clinical predictors of MDA response at week 24 were evaluated through multivariate analysis. RESULTS: At baseline, 124/126 (98%) and 54/126 (43%) patients showed peripheral and axial involvement, respectively; 110 (87%) patients were intolerant or resistant to biologic DMARDs.  At 24 weeks, MDA status, DAPSA remission, and ASDAS-CRP inactive disease were achieved in 47%, 23%, and 48% of patients, respectively. Minor, moderate, and major DAPSA improvement was observed in 67%, 39%, and 23%, respectively; while 65% and 35% achieved ASDAS-CRP CII and MI, respectively. The mean change from baseline was 15.9 ± 13.5 (p < 0.001) for DAPSA and 1.21 ± 0.97 (p < 0.001) for ASDAS-CRP. Thirteen patients (10%) discontinued UPA due to a lack of efficacy or non-serious adverse events. No serious adverse events were observed. Male gender (OR 2.54, 95% CI 1.03-6.25 p = 0.043), being naïve to biological DMARDs (OR 4.13, 95% CI 1.34-12.71, p = 0.013) and elevated baseline CRP (OR 2.49, 95% CI 1.02-6.12, p = 0.046) were associated with MDA response at week 24. CONCLUSIONS: This is one of the first real-life studies supporting the effectiveness of UPA and its safety profile in PsA patients. Furthermore, the study identifies predictors of MDA response to UPA treatment at 6 months.

The ATTRACT study: screening for the early identification of axial psoriatic arthritis in a cohort of Italian psoriatic patients.

OBJECTIVE: There is growing interest in the early identification of patients with axial psoriatic arthritis (axPsA). We aimed to evaluate whether a dermatology-based screening strategy could help to identify axPsA patients. METHODS: The dermatologist-centered screening (DCS) questionnaire was administrated by Dermatologists to consecutive patients fulfilling the inclusion criteria (1. age ≥ 18 years and 2. clinical diagnosis of psoriasis made by a dermatologist) to identify patients eligible (affirmative answers 1-3c of the DCS) for rheumatological evaluation. Clinical, laboratory, genetic, and imaging data were collected from all referred patients. RESULTS: Among the 365 patients screened, 265 fulfilled the inclusion criteria and 124/265 (46.8%) were eligible for rheumatological referral. Diagnosis of axPsA, with or without peripheral PsA (pPsA), was made in 36/124 (29.0%) patients; pPsA without axial involvement was found in 21/124 (16.9%) patients. Back pain at screening was recorded in 174 (66%) patients, with 158 (60%) reporting a back pain duration longer than 3 months, and 140 (53%) reporting back pain onset before the age of 45. Active inflammatory and/or structural post-inflammatory changes in the sacroiliac joints and/or spine were observed in all axPsA patients.Patients with PsA showed a numerically longer duration of back pain and higher CRP levels in comparison with patients with Pso without PsA. CONCLUSION: The DCS tool proved to be a valuable screening strategy for detecting and characterizing patients with axPsA in a real-life cohort of psoriasis patients in a dermatological setting and helped to identify a substantial number of patients affected by undiagnosed pPsA.

Skin Gene Expression Profiles in Systemic Sclerosis: From Clinical Stratification to Precision Medicine.

Systemic sclerosis, also known as scleroderma or SSc, is a condition characterized by significant heterogeneity in clinical presentation, disease progression, and response to treatment. Consequently, the design of clinical trials to successfully identify effective therapeutic interventions poses a major challenge. Recent advancements in skin molecular profiling technologies and stratification techniques have enabled the identification of patient subgroups that may be relevant for personalized treatment approaches. This narrative review aims at providing an overview of the current status of skin gene expression analysis using computational biology approaches and highlights the benefits of stratifying patients upon their skin gene signatures. Such stratification has the potential to lead toward a precision medicine approach in the management of SSc.

Screening and Analysis of Possible Drugs Binding to PDGFRα: A Molecular Modeling Study.

The platelet-derived growth factor receptor (PDGFR) is a membrane tyrosine kinase receptor involved in several metabolic pathways, not only physiological but also pathological, as in tumor progression, immune-mediated diseases, and viral diseases. Considering this macromolecule as a druggable target for modulation/inhibition of these conditions, the aim of this work was to find new ligands or new information to design novel effective drugs. We performed an initial interaction screening with the human intracellular PDGFRα of about 7200 drugs and natural compounds contained in 5 independent databases/libraries implemented in the MTiOpenScreen web server. After the selection of 27 compounds, a structural analysis of the obtained complexes was performed. Three-dimensional quantitative structure-activity relationship (3D-QSAR) and absorption, distribution, metabolism, excretion, and toxicity (ADMET) analyses were also performed to understand the physicochemical properties of identified compounds to increase affinity and selectivity for PDGFRα. Among these 27 compounds, the drugs Bafetinib, Radotinib, Flumatinib, and Imatinib showed higher affinity for this tyrosine kinase receptor, lying in the nanomolar order, while the natural products included in this group, such as curcumin, luteolin, and epigallocatechin gallate (EGCG), showed sub-micromolar affinities. Although experimental studies are mandatory to fully understand the mechanisms behind PDGFRα inhibitors, the structural information obtained through this study could provide useful insight into the future development of more effective and targeted treatments for PDGFRα-related diseases, such as cancer and fibrosis.

Real-life efficacy and safety of nintedanib in systemic sclerosis-interstitial lung disease: data from an Italian multicentre study.

INTRODUCTION: Nintedanib (NTD) has been shown to be effective in systemic sclerosis (SSc)-interstitial lung disease (ILD). Here we describe the efficacy and safety of NTD in a real-life setting. METHODS: Patients with SSc-ILD treated with NTD were retrospectively evaluated at 12 months prior to NTD introduction; at baseline and at 12 months after NTD introduction. The following parameters were recorded: SSc clinical features, NTD tolerability, pulmonary function tests and modified Rodnan skin score (mRSS). RESULTS: 90 patients with SSc-ILD (65% female, mean age 57.6±13.4 years, mean disease duration 8.8±7.6 years) were identified. The majority were positive for anti-topoisomerase I (75%) and 77 (85%) patients were on immunosuppressants. A significant decline in %predicted forced vital capacity (%pFVC) in the 12 months prior to NTD introduction was observed in 60%. At 12 months after NTD introduction, follow-up data were available for 40 (44%) patients and they showed a stabilisation in %pFVC (64±14 to 62±19, p=0.416). The percentage of patients with significant lung progression at 12 months was significantly lower compared with the previous 12 months (60% vs 17.5%, p=0.007). No significant mRSS change was observed. Gastrointestinal (GI) side effects were recorded in 35 (39%) patients. After a mean time of 3.6±3.1 months, NTD was maintained after dose adjustment in 23 (25%) patients. In nine (10%) patients, NTD was stopped after a median time of 4.5 (1-6) months. During the follow-up, four patients died. CONCLUSIONS: In a real-life clinical scenario, NTD, in combination with immunosuppressants, may stabilise lung function. GI side effects are frequent and NTD dose adjustment may be necessary to retain the drug in patients with SSc-ILD.

6 and 12 month outcomes in patients following COVID-19-related hospitalization: a prospective monocentric study.

The long-term consequences of COVID-19 in those who recover from acute infection requiring hospitalization have not been defined yet. In this study, we aim to describe the long-term symptoms and respiratory outcomes over 12 months in patients hospitalized for severe COVID-19. In this prospective cohort study, patients admitted to hospital for severe COVID-19 were prospectively followed up at 6 and 12 months after discharge from the Hospital of Fermo, Italy. Patients were interviewed for persisting symptoms and underwent physical examination, routine blood test, pulmonary function tests, chest high-resolution CT (HRCT), and 6 min walking test. A total of 64 patients were evaluated and participated in this study. The mean age of participants was 68 years, 41 (64%) were males, and the median body mass index (BMI) was 26 kg/m2. After 6 months, 36% of patients reported persistent dyspnea, 37.5% persistent fatigue, 30.6% hair loss, 14% arthralgia and 11% memory and attention deficits. The rate of these symptoms reduced at the 12 month follow-up. At least 50% of the patients reported anxiety and depression symptoms. At 6 months 57.4% of patients showed reduced DLCO and 21.3% reduced FVC% and improvement at 12 months was noted for FVC but not for DLCO and TLC. Persistent radiographic abnormalities, most commonly ground-glass opacities and interstitial changes, were observed at both timepoints in many patients. Long-term symptoms and pulmonary deficits are common in patients admitted for severe COVID-19. Further studies are needed to assess the clinical significance of long-term consequences of severe COVID-19.

PDGF/PDGFR: A Possible Molecular Target in Scleroderma Fibrosis.

Systemic sclerosis (SSc) is a clinically heterogeneous disorder of the connective tissue characterized by vascular alterations, immune/inflammatory manifestations, and organ fibrosis. SSc pathogenesis is complex and still poorly understood. Therefore, effective therapies are lacking and remain nonspecific and limited to disease symptoms. In the last few years, many molecular and cellular mediators of SSc fibrosis have been described, providing new potential options for targeted therapies. In this review: (i) we focused on the PDGF/PDGFR pathway as key signaling molecules in the development of tissue fibrosis; (ii) we highlighted the possible role of stimulatory anti-PDGFRα autoantibodies in the pathogenesis of SSc; (iii) we reported the most promising PDGF/PDGFR targeting therapies.

SARS-COV-2 Infection, Vaccination, and Immune-Mediated Diseases: Results of a Single-Center Retrospective Study.

Objectives: The relationship between infections or vaccine antigens and exacerbations or new onset of immune-mediated diseases (IMDs) has long been known. In this observational study, conducted during the COVID-19 pandemic, we evaluated the onset of clinical and laboratory immune manifestations related to COVID-19 or SARS-CoV-2 vaccination. Methods: Four groups of patients were evaluated: A) 584 COVID-19 inpatients hospitalized from March 2020 to June 2020 and from November 2020 to May 2021; B) 135 outpatients with previous SARS-CoV-2 infection, assessed within 6 months of recovery; C) outpatients with IMDs in remission and flared after SARS-COV-2 infection; D) outpatients with symptoms of probable immune-mediated origin after SARS-CoV-2 vaccination. Results: In cohort A we observed n. 28 (4.8%) arthralgia/myalgia, n. 2 (0.3%) arthritis, n. 3 (0.5%) pericarditis, n. 1 (0.2%) myocarditis, n. 11 (1.9%) thrombocytopenia or pancytopenia, and in the follow up cohort B we identified 9 (6.7%) cases of newly diagnosed IMDs after the recovery from COVID-19. In all cases, serological alterations were not observed.In cohort C we observed n.5 flares of pre-existing IMD after SARS-COV2 infection, and in the cohort D n. 13 IMD temporally close with SARS-CoV-2 vaccination in 8 healthy subjects (with clinical classifiable IMD-like presentation) and in 5 patients affected by an anamnestic IMD. Also in these latter cases, except in 2 healthy subjects, there were not found serological alterations specific of a classifiable IMD. Conclusions: This study suggests that the interplay between SARS-CoV-2 and the host may induce complex immune-mediated reactions, probably induced by the anti-spike antibodies, in healthy people and IMD patients without specific serological autoimmunity. Moreover, our data suggest that the anti-SARS-CoV-2 antibodies generated by the vaccination may cause in healthy subjects' clinical manifestations similar to well-definite IMDs. These findings support the hypothesis that SARS-Cov2 infection in COVID-19 induce an innate and adaptive immune response that may be both responsible of the symptoms correlated with the occurrence of the IMDs described in our study. And, in this context, the IMDs observed in healthy people in close temporal correlation with the vaccination suggest that the anti-Spike antibodies may play a key role in the induction of an abnormal and deregulated immune response.

Discharge from the emergency department and early hospital revaluation in patients with COVID-19 pneumonia: a prospective study.

OBJECTIVE: The national health systems are currently facing the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. We assessed the efficacy of outpatient management for patients with SARS-CoV-2 related pneumonia at risk of progression after discharge from the emergency department. METHODS: This was a single-center prospective study. We enrolled patients with confirmed SARS-CoV-2 pneumonia, without hypoxemic respiratory failure, and at least one of the following: age ≥ 65 years or the presence of relevant comorbidities or pneumonia extension > 25% on high resolution computed tomography. Patients with pneumonia extension > 50% were excluded. An ambulatory visit was performed after at least 48 hours, when patients were either discharged, admitted, or deferred for a further visit. As a control, we evaluated a comparable historical cohort of hospitalized patients. RESULTS: A total of 84 patients were enrolled (51 male patients; mean age, 62.8 years). Two-thirds of the patients had at least one comorbidity and 41.6% had a lung involvement > 25% on high resolution computed tomography; the mean duration of symptoms was 8.0 ± 3.0 days, and the mean PaO2/FiO2 ratio was 357.5 ± 38.6. At the end of the follow-up period, 69 patients had been discharged, and 15 were hospitalized (mean stay of 6 days). Older age and higher National Early Warning Score 2 were significant predictors of hospitalization at the first follow-up visit. One hospitalized patient died of septic shock. In the control group, the mean hospital stay was 8 days. CONCLUSION: Adopting a "discharge and early revaluation" strategy appears to be safe, feasible, and may optimize hospital resources during the SARS-CoV-2 pandemic.

Systemic Sclerosis: From Pathophysiology to Novel Therapeutic Approaches.

Systemic sclerosis (SSc) is a systemic, immune-mediated chronic disorder characterized by small vessel alterations and progressive fibrosis of the skin and internal organs. The combination of a predisposing genetic background and triggering factors that causes a persistent activation of immune system at microvascular and tissue level is thought to be the pathogenetic driver of SSc. Endothelial alterations with subsequent myofibroblast activation, excessive extracellular matrix (ECM) deposition, and unrestrained tissue fibrosis are the pathogenetic steps responsible for the clinical manifestations of this disease, which can be highly heterogeneous according to the different entity of each pathogenic step in individual subjects. Although substantial progress has been made in the management of SSc in recent years, disease-modifying therapies are still lacking. Several molecular pathways involved in SSc pathogenesis are currently under evaluation as possible therapeutic targets in clinical trials. These include drugs targeting fibrotic and metabolic pathways (e.g., TGF-ß, autotaxin/LPA, melanocortin, and mTOR), as well as molecules and cells involved in the persistent activation of the immune system (e.g., IL4/IL13, IL23, JAK/STAT, B cells, and plasma cells). In this review, we provide an overview of the most promising therapeutic targets that could improve the future clinical management of SSc.

Current Take on Systemic Sclerosis Patients' Vaccination Recommendations.

Systemic sclerosis (SSc) is a rare autoimmune inflammatory rheumatic disease. The prevalence of SSc ranges from 7 to 700 cases per million worldwide. Due to multiple organ involvement and constant inflammatory state, this group of patients presents an increased risk of infectious diseases. This paper aimed to gather the up-to-date evidence on vaccination strategies for patients with SSc and to be a useful tool for the prevention and management of infectious diseases. The authors conducted a scoping review in which each paragraph presents data on a specific vaccine's safety, immunogenicity, and efficacy. The work deals with the following topics: SARS-CoV-2, seasonal influenza, S. pneumoniae, HAV, HBV, HZV, N. meningitidis, H. influenzae, HPV, and diphtheria-tetanus-pertussis.

Inflammatory bowel disease manifestations in spondyloarthritis: considerations for the clinician.

INTRODUCTION: Spondyloarthropathies (SpA) are a group of inflammatory arthritis that can involve the spine and/or peripheral joints. Extra-articular manifestations, such as inflammatory bowel disease (IBD), are frequently observed within the clinical manifestations of SpA and are part of the SpA classification criteria. Evidence of IBD is observed in about 6-7% of SpA patients, and a silent, microscopic gut inflammation, could be present in up to 50% of patients. From a pathogenetic point of view, dysregulated microbiome and migration of T lymphocytes and other cells from gut to the joint ('gut-joint' axis) has been recognized, in the context of a common genetic background. AREAS COVERED: The aim of this paper is to narratively review the recent evidences on the epidemiology, classification, clinical findings, pathogenesis, diagnosis, and treatment of IBD in patients with SpA and to provide advices for both rheumatologist and gastroenterologist in the management of IBD in SpA. EXPERT OPINION: IBD manifestations in SpA frequently increase the burden of the disease and represent a clinical challenge, especially for the diagnosis, assessment, and treatment of patients affected by those conditions. New treatment strategies targeting both articular and intestinal manifestations are now available and may lead to a better outcome.

New Insights in Physical Therapy and Rehabilitation in Psoriatic Arthritis: A Review.

Psoriatic arthritis (PsA) is a complex, multiform and chronic inflammatory disease characterized by the association of psoriasis and arthritis with other musculoskeletal and extra-articular manifestations. The treatment of PsA is rapidly evolving due to the introduction of new biologic and small-molecule drugs, and the aim of treatment is to induce a condition of remission or low disease activity in all disease domains. However, unmet treatment needs still persist for those patients with impaired function, reduced quality of life or comorbidities. In this context, physical therapy and rehabilitation could provide additional benefits by reducing disease activity and improving function. Although a large number of studies have assessed the role of physical therapy and exercise in other forms of chronic inflammatory arthritis, such as axial spondyloarthritis and rheumatoid arthritis, evidence on their effect on persons with PsA is still lacking. However, some studies have reported the potential positive role of physical therapy on the different disease domains of PsA, in helping to improve disease activity, prevent or improve articular impairment, improve pain management and improve quality of life. Here, we review current evidence on physical therapy, exercise and rehabilitation in patients with PsA. In particular, we review the literature focusing on each domain, to provide evidence of efficacy and effectiveness of exercise and rehabilitation on skin, peripheral arthritis, axial involvement, dactylitis, enthesitis and comorbidities.

Diagnosis and management of leukocytoclastic vasculitis.

Leukocytoclastic vasculitis (LCV) is a histopathologic description of a common form of small vessel vasculitis (SVV), that can be found in various types of vasculitis affecting the skin and internal organs. The leading clinical presentation of LCV is palpable purpura and the diagnosis relies on histopathological examination, in which the inflammatory infiltrate is composed of neutrophils with fibrinoid necrosis and disintegration of nuclei into fragments ("leukocytoclasia"). Several medications can cause LCV, as well as infections, or malignancy. Among systemic diseases, the most frequently associated with LCV are ANCA-associated vasculitides, connective tissue diseases, cryoglobulinemic vasculitis, IgA vasculitis (formerly known as Henoch-Schonlein purpura) and hypocomplementemic urticarial vasculitis (HUV). When LCV is suspected, an extensive workout is usually necessary to determine whether the process is skin-limited, or expression of a systemic vasculitis or disease. A comprehensive history and detailed physical examination must be performed; platelet count, renal function and urinalysis, serological tests for hepatitis B and C viruses, autoantibodies (anti-nuclear antibodies and anti-neutrophil cytoplasmic antibodies), complement fractions and IgA staining in biopsy specimens are part of the usual workout of LCV. The treatment is mainly focused on symptom management, based on rest (avoiding standing or walking), low dose corticosteroids, colchicine or different unproven therapies, if skin-limited. When a medication is the cause, the prognosis is favorable and the discontinuation of the culprit drug is usually resolutive. Conversely, when a systemic vasculitis is the cause of LCV, higher doses of corticosteroids or immunosuppressive agents are required, according to the severity of organ involvement and the underlying associated disease.

Dual-energy computed tomography for the detection of sacroiliac joints bone marrow oedema in patients with axial spondyloarthritis.

OBJECTIVES: To investigate the diagnostic performance of dual-energy computed tomography (DECT) in detection bone marrow oedema (BME) in patients with sacroiliitis associated with axial spondyloarthritis (axial SpA). METHODS: Patients with axial SpA according to the ASAS criteria underwent DECT and 1.5-T magnetic resonance imaging (MRI). DECT was post-processed for generating virtual non-calcium (VNCa) images. The presence of abnormal bone marrow attenuation was scored on DECT VNCa images and MRI using a four-point classification system: 0-1 = absent or non-significant oedema, 2 = oedema present in a third of the articular surface, 3 = oedema present in 2/3 of the articular surface, 4 = diffuse oedema throughout the articular surface. Diagnostic accuracy values for BME were calculated for DECT images (quantitative assessment) by using receiver operating characteristic (ROC) curves analysis, applying MRI as gold standard. RESULTS: Eighty sacroiliac joints from 40 axial SpA patients were included for study analysis, and 36 sacroiliac joints (45%) were classified as having BME at MRI and compared to DECT. Sensitivity, specificity, and positive likelihood ratio (LR+) in the identification of BME at DECT were 90.0%, 92.8%, and 12.6 respectively. Negative LR was 0.11, positive predictive value 93.1%, and negative predictive value 89.7%. The area under the curve (AUC) was 0.953 in the differentiation of the presence of BME. A cut-off value of -1.6 HU (Youden's index = 0.828) yielded a sensitivity of 90.0% and specificity of 92.8%, with an LR+ of 12.6, in the detection of BME in the sacroiliac joints. CONCLUSIONS: DECT VNCa images had good diagnostic performance in the evaluation of the extent of BME in patients with sacroiliitis associated with axial SpA.

Safety of intermediate dose of low molecular weight heparin in COVID-19 patients.

Coagulopathy represents one of the most important determinants of morbidity and mortality in coronavirus disease-19 (COVID-19). Whether standard thromboprophylaxis is sufficient or higher doses are needed, especially in severe patients, is unknown. To evaluate the safety of intermediate dose regimens of low-weight molecular heparin (LWMH) in COVID-19 patients with pneumonia, particularly in older patients. We retrospectively evaluated 105 hospitalized patients (61 M, 44 F; mean age 73.7 years) treated with subcutaneous enoxaparin: 80 mg/day in normal weight and mild-to-moderate impair or normal renal function; 40 mg/day in severe chronic renal failure or low bodyweight (< 45 kg); 100 mg/day if bodyweight was higher than 100 kg. All the patients had radiologically confirmed pneumonia and 63.8% had severe COVID-19. None of the patients had fatal haemorrhage; two (1.9%) patients had a major bleeding event (one spontaneous hematoma and one gastrointestinal bleeding). Only 6.7% of patients needed transfusions of red blood cells. One thrombotic event (pulmonary embolism) was observed. When compared to younger patients, patients older than 85 years had a higher mortality (40% vs 13.3%), but not an increased risk of bleeding or need for blood transfusion. The use of an intermediate dose of LWMH appears to be feasible and data suggest safety in COVID-19 patients, although further studies are needed.