Asymptomatic peripheral artery disease and antiplatelet management.

Peripheral arterial disease (PAD) is a hallmark of generalized atherosclerosis. Depending on the specific diagnostic criteria that are being used, the prevalence of PAD may be as high as 30 % in the population of people 70 or more years old. Unfortunately, although PAD is prevalent and has many important consequences for patients, it is often under-detected and under-treated by primary care physicians. The aim of this review is to provide an overview of the available literature on epidemiology and antiplatelets management of PAD patients. In particular, we focus on the "hidden" side of PAD burden, the asymptomatic patients, who are at high risk of negative cardiovascular outcomes. Identification of such PAD patients is therefore an important clinical goal to reduce mortality and morbidity and reduce the social cost of atherosclerotic disease. Early screening of PAD and an evidence-based antithrombotic approach are also discussed as potential strategies to counteract the negative impact of such condition in general population, as well as, in patients with other cardiovascular diseases.

Real life use of prostacyclin analog (iloprost), a multi-centric survey data from the Scleroderma study group Emilia Romagna (Sclero-RER) and review of the literature.

BACKGROUND AND AIM: Iloprost is recommend worldwide for the treatment of RP and the healing of DUs. The aim of this study is to report the regimens of Iloprost administered in different rheumatological centers within the same regional Health System Methods: A questionnaire exploring different items related to the use of Iloprost was developed and reviewed by three expert rheumatologists. The questionnaire was distributed as an online survey to all local SSc referral centers in Emilia-Romagna (Italy). Data are reported as percentage or median with interquartile range (IQR), as appropriate. An updated review of world literature on this topic was also carried out. RESULTS: All the invited centers completed the survey. There were both local (8) and university hospitals (4). The majority (58%) had a rheumatologist as head physician. All centers used Iloprost: a single monthly administration was the most common treatment (75%). The cycle lasted 1 [IQR 1-2] days with a 0.5-2.0 ng/Kg/min dose according to the drug tolerance of the patients. There were overall 68 spots (beds, reclining armchair, or simple armchair); 2.0 [1.5-4.0] patients were able to receive Iloprost at the same time. University Hospitals had more physicians at their disposal than local hospitals but less paramedic personnel (respectively: 1.8 vs 1.2 physicians, 1.5 vs 2.1 nurses). CONCLUSIONS: These observations were in line with the majority of previous studies reporting different regimens, comparing similar (but not identical) dose and schedule administration, however, despite differences being at times substantial, no standard infusion method is yet available.

Pulmonary embolism and renal artery thrombosis in a patient with patent foramen ovale.

BACKGROUND AND AIM: Paradoxical embolism is a rare condition in which a thrombus migrates from the venous system to the arterial circulation, usually through a patent foramen ovale (PFO). Pulmonary embolism (PE) and isolated occlusion of one renal artery has been seldom reported. METHODS: We describe a case of a 47-year old white man with a one-month history of exertional dyspnea who was admitted to our hospital for  severe pain in the right lumbar region. RESULTS: A computed tomography showed  PE and a thrombotic occlusion of the right renal artery. A trans-thoracic echocardiogram documented a PFO with right to left shunt. Magnetic resonance imaging of the brain and venous compression ultrasonography of the lower extremities were normal. Therapeutic anticoagulation was started. CONCLUSIONS: Pulmonary embolism and thrombotic occlusion of one renal artery is a rare manifestation of paradoxical embolism. Exertional dyspnea is an atypical manifestation of PE and can delay the diagnosis.

Management of Sjögren's Syndrome: Present Issues and Future Perspectives.

In view of the new possibilities for the treatment of primary Sjögren's syndrome (pSS) given by the availability of new biotechnological agents targeting the various molecular and cellular actors of the pathological process of the disease, classification criteria aimed at selecting patients to be enrolled in therapeutic trials, and validated outcome measures to be used as response criteria to these new therapies, have been developed and validated in the last decades. Unfortunately, the therapeutic trials so far completed with these new treatments have yielded unsatisfactory or only partially positive results. The main issues that have been evoked to justify the poor results of the new therapeutic attempts are: (i) the extreme variability of the disease phenotypes of the patients enrolled in the trials, which are dependent on different underlying patterns of biological mechanisms, (ii) the fact that the disease has a long indolent course, and that most of the enrolled patients might already have irreversible clinical features. The advances in the research of new disease biomarkers that can better distinguish the different clinical phenotypes of patients and diagnose the disease in an earlier phase are also discussed.

Instruments for Outcome Evaluation of Specific Domains in Primary Sjögren's Syndrome.

Primary Sjögren's syndrome (pSS) is a systemic autoimmune disorder characterized by very heterogeneous features. The spectrum of this disorder may vary from benign but disabling symptoms such as dryness, due to lachrymal and salivary involvement, pain and fatigue, to systemic, potentially severe, manifestations that may involve any organ. In recent decades, the arrival of biotechnological therapy has offered new opportunities for the treatment of this-until now-orphan disease. Currently, the possible use of these new drugs in therapeutic trials has made it necessary to have reliable outcome measures to evaluate their efficacy in this disease. A great effort has been made in multicenter, often multinational, studies to develop and validate instruments capable of assessing the different disease-related features. The adoption in therapeutic trials of the newly developed outcome measures aimed at assessing systemic features and patient reported symptoms has often yielded disappointing results. These negative data have been ascribed, on the one hand, to the trial design not being completely appropriate, and, on the other hand, to the fact that a single instrument may be not sufficient to cover the great clinical heterogeneity of the disease features. There is now growing belief that composite end points that include instruments that are able to assess the various aspects of the disease may be more properly and successfully used in future therapeutic trials.

The Role of Interferons in the Pathogenesis of Sjögren's Syndrome and Future Therapeutic Perspectives.

There is a great deal of evidence pointing to interferons (IFNs) as being key cytokines in the pathogenesis of different systemic autoimmune diseases, including primary Sjögren's syndrome (pSS). In this disease, a large number of studies have shown that an overexpression of type I IFN, the 'so-called' type I IFN signature, is present in peripheral blood mononuclear cells, and that this finding is associated with the development of systemic extra-glandular manifestations, and a substantial production of autoantibodies and inflammatory cytokines. In contrast, the absence or a milder expression of type I IFN signature and low level of inflammatory cytokines characterizes patients with a different clinical phenotype, where the disease is limited to glandular involvement and often marked by the presence of widespread pain and depression. The role of type II (IFNγ) in this subset of pSS patients, together with the potentially related activation of completely different immunological and metabolic pathways, are emerging issues. Expression of both types of IFNs has also been shown in target tissues, namely in minor salivary glands where a predominance of type II IFN signature appeared to have a certain association with the development of lymphoma. In view of the role played by IFN overexpression in the development and progression of pSS, inhibition or modulation of IFN signaling has been regarded as a potential target for the therapeutic approach. A number of therapeutic compounds with variable mechanisms of action have been tested or are under consideration for the treatment of patients with pSS.

Taking care of systemic sclerosis patients during COVID-19 pandemic: rethink the clinical activity.

COVID-19 outbreak has quickly spread worldwide, causing a high pressure on the health-care system. In Italy, from March 8, 2020, all the deferrable clinical activities have been suspended to increase the health care offer for COVID-19 patients. The hospital organization has been modified also in order to assure non-COVID-19 patients assistance. The Scleroderma Unit of ASST Pini-CTO Hospital, in Milan, in the region mostly hit by SARS-CoV-2 in Italy, follows more than 600 patients affected by systemic sclerosis (SSc). Patients with SSc need a close follow-up with a regular screening of organ involvement and frequent intravenous treatments. All SSc patients have been educated about ministerial directives to limit COVID-19 spread. The organization of our Scleroderma Unit has been quickly rethought to assure SSc patients assistance in safety for them and for health-care workers during urgent visits or infusion therapies. Using electronic way of communication with frequent virtual contact and guarantying home deliveries of some therapies, we allowed a continuity of care also outside the Hospital.

Quantification of Ground Glass Opacities Can Be Useful to Describe Disease Activity in Systemic Sclerosis.

Interstitial lung disease (ILD) is the main cause of death in systemic sclerosis (SSc) patients. Usually, patients have lung involvement characterized by ground glass opacities (GGOs), but honeycombing (HC) is also possible. The Wells score is a semi-quantitative index, which is able to assess ILD by distinguishing its main components. The aim of this work is to evaluate the Wells score in relation to the disease activity (DA) index. We enrolled 40 consecutive SSc-ILD patients (26 diffuse cutaneous form, dcSSc, and 14 limited form, lcSSc). All patients were evaluated by the European Scleroderma Study Group (ESSG) index, high-resolution computed tomography, transthoracic echocardiogram, pulmonary function tests (PTSs), and nailfold videocapillaroscopy for the number of microhemorrhages (NEMO) score. In our study, the total extent of ILD (TE-ILD), fibrosis and GGOs correlated with dyspnea (p = 0.03, 0.01 and 0.01 respectively), but not with the ESSG index. Considering only the dcSSc patients, TE-ILD and GGOs correlated with the ESSG index (r = 0.5 p = 0.009), while fibrosis grade correlated with disease duration and systolic pulmonary artery pressure. In conclusion, our data suggest that GGO correlates with DA, while fibrosis may be a sign of disease damage. The quantification of pulmonary involvement using the Wells score can be a useful tool for assessing the appropriate treatment in SSc patients.

High NEMO score values in nailfold videocapillaroscopy are associated with the subsequent development of ischaemic digital ulcers in patients with systemic sclerosis.

BACKGROUND: Nailfold videocapillaroscopy (NVC) is a feasible method that allows the observation of the microvascular changes that mark the course of systemic sclerosis (SSc). In previous studies, we demonstrated that the NEMO score, i.e. the cumulative number of microhaemorrhages and microthromboses, is a good indicator of the steady-state level and overtime changes of disease activity (DA) in SSc. OBJECTIVES: To verify whether high NEMO scores, which mirror a very active microvascular derangement in the fingers, may be associated with the subsequent development of ischaemic digital ulcers (IDUs). METHODS: The NEMO score was assessed at baseline (T0) in 98 patients with SSc, all classified according to the ACR-EULAR criteria. Of them, 90 were females, 48 had the limited and 50 had the diffuse cutaneous variant of SSc. Afterwards, the patients were closely followed up for 2 years, and the appearance of new IDUs recorded at any time of the follow-up. The T0-NEMO score values of patients who developed IDUs were compared to those of patients who did not. A receiver operating curve (ROC) was constructed, and the area under the curve (AUC) calculated by plotting the sensitivity and 1-specificity of the different NEMO score values in predicting the subsequent development of IDUs. RESULTS: During the follow-up, 38 out of 98 patients developed one or more IDUs. The NEMO score at T0 was significantly higher in those who developed IDUs with respect to those who did not [median 14.5 (95% CI 11.0-21.5) and 4.5 (95% CI 4.0-6.0), respectively, p < 0.0001]. The ROC curve derived from different T0-NEMO score values had an AUC of 0.79 (95% CI 0.69-0.86, p < 0.0001). A NEMO score of ≥ 12 had a sensitivity of 83.3% (95% CI 71.5-91.7) and a specificity of 63.2% (95% CI 46.0-78.2), with positive (P) and negative (N) predictive (PV) values of 58.9% (95% CI 44.7-72.2) and 85.6% (71.8-94.4), respectively. A NEMO score of ≥ 16 had a sensitivity of 95.0% (95% CI 86.1-99.0) and a NPV of 93.4% (77.5-99.2). CONCLUSIONS: Being a valid tool to measure DA levels in SSc, the NEMO score also appears to be closely related to the subsequent development of IDUs in this disease.

Nailfold Videocapillaroscopy is a Useful Tool to Recognize Definite Forms of Systemic Sclerosis and Idiopathic Inflammatory Myositis in Interstitial Lung Disease Patients.

Nailfold videocapillaroscopy (NVC) is an easy tool used for the assessment of patients with Raynaud's phenomenon (RP) as possibly associated with systemic sclerosis (SSc). Recent insights have also highlighted its role in the diagnostic assessment of idiopathic inflammatory myopathies (IIMs). The aim of this study is to describe the diagnostic role of NVC in a series of 361 consecutive patients with interstitial lung disease (ILD). All the patients were assessed by clinical pulmonary and rheumatic examinations, blood exams, high-resolution computed tomography and NVC. NVC was considered positive only in the presence of avascular areas or giant capillaries, but also, the presence of bushy capillaries (BCs) was recorded. NVC was positive in 17.7% of ILD patients and in 78.1% of ILD patients associated with a diagnosis of connective tissue disease (CTD). In 25% of SSc-ILD patients, NVC proved necessary for a correct diagnosis. The presence of BCs and/or NVC positivity in ILD patients with normal levels of creatine phosphokinase is associated with amyopathic IIM, regardless the presence of RP. In conclusion, NVC is useful for the diagnostic assessment of incomplete forms of CTD and in amyopathic IIMs. NVC should be considered in the diagnostic assessment of ILD patients regardless of the presence of RP.

Patients with Interstitial Lung Disease Secondary to Autoimmune Diseases: How to Recognize Them?

The diagnostic assessment of patients with Interstitial Lung Disease (ILD) can be challenging due to the large number of possible causes. Moreover, the diagnostic approach can be limited by the severity of the disease, which may not allow invasive exams. To overcome this issue, the referral centers for ILD organized Multidisciplinary Teams (MDTs), including physicians and experts in complementary discipline, to discuss the management of doubtful cases of ILD. MDT is currently considered the gold standard for ILD diagnosis, but it is not often simple to organize and, furthermore, rheumatologists are still not always included. In fact, even if rheumatologic conditions represent a common cause of ILD, they are sometimes difficult to recognize, considering the variegated clinical features and their association with all possible radiographic patterns of ILD. The first objective of this review is to describe the clinical, laboratory, and instrumental tests that can drive a diagnosis toward a possible rheumatic disease. The secondary objective is to propose a set of first-line tests to perform in all patients in order to recognize any possible rheumatic conditions underlying ILD.

Impact of COVID-19 outbreak in an Italian cohort of patients with systemic sclerosis.

BACKGROUND: Mortality rate in patients infected by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) can be related to the presence of comorbidities like diabetes, cardiovascular and pulmonary diseases. On the contrary, few data exist on the impact of CoronaVirus Disease 2019 (COVID-19) on patients with rheumatic disorders, namely in those having pulmonary involvement and treated with immunosuppressive agents. The present survey is aimed at knowing the impact of COVID-19 in a cohort of patients with systemic sclerosis (SSc). METHODS: Telephone interviews were carried out during the COVID-19 outbreak in patients with SSc followed in a Rheumatic Disease Unit in Italy. Patients were asked for confirmed SARS-CoV-2 infection, symptoms suggestive of COVID-19, and modification of their therapy. RESULTS: A total number of 526 patients with SSc were contacted and interviewed. Of them, 270 and 256 had limited cutaneous and diffuse cutaneous SSc, respectively. Interstitial lung disease (ILD) was present in 45% of patients and most of them (68.2%) were treated with immunosuppressive therapy. Only two patients were hospitalized for COVID-19-related pneumonia, and one of them died despite invasive ventilator support. An additional 11 patients reported flu-like symptoms compatible with a mild form of COVID-19. Nobody modified the therapy during the COVID-19 outbreak. CONCLUSION: Despite the large prevalence of ILD and immunosuppressive therapies, which can be considered risk factors for the occurrence and severity of incidental viral infections, the impact of COVID-19, in terms of mortality rate and morbidity, does not appear particularly severe in this large cohort of patients with SSc. Possible mechanisms influencing this figure are discussed.

The Model for Early COvid-19 Recognition (MECOR) Score: A Proof-of-Concept for a Simple and Low-Cost Tool to Recognize a Possible Viral Etiology in Community-Acquired Pneumonia Patients during COVID-19 Outbreak.

This study aims to assess the peripheral blood cell count "signature" of Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) to discriminate promptly between COronaVIrus Disease 19 (COVID-19) and community-acquired pneumonia (CAP). We designed a retrospective case-control study, enrolling 525 patients (283 COVID-19 and 242 with CAP). All patients had a fever and at least one of the following signs: cough, chest pain, or dyspnea. We excluded patients treated with immunosuppressants, steroids, or affected by diseases known to modify blood cell count. COVID-19 patients showed a significant reduction in white blood cells (neutrophils, lymphocytes, monocytes, eosinophils) and platelets. We studied these parameters univariately, combined the significant ones in a multivariate model (AUROC 0.86, Nagelkerke PSEUDO-R2 0.5, Hosmer-Lemeshow p-value 0.9) and examined its discriminative performance in an internally-randomized validation cohort (AUROC 0.84). The cut-off selected according to Youden's Index (-0.13) showed a sensitivity of 84% and a specificity of 72% in the training cohort, and a sensitivity of 88% and a specificity of 73% in the validation cohort. In addition, we determined the probability of having COVID-19 pneumonia for each Model for possible Early COvid-19 Recognition (MECOR) Score value. In conclusion, our model could provide a simple, rapid, and cheap tool for prompt COVID-19 diagnostic triage in patients with CAP. The actual effectiveness should be evaluated in further, prospective studies also involving COVID-19 patients with negative nasopharyngeal swabs.

Interstitial Lung Disease in patients with Polymyalgia Rheumatica: A case series.

INTRODUCTION: Severe morning stiffness with painful involvement of the girdles are often referred by patients with Interstitial Lung Disease (ILD), but the association between ILD and Polymyalgia Rheumatica (PMR) is rarely reported. The purpose of the work is to describe a series of patients classified as having PMR with ILD. MATERIAL AND METHODS: We retrospectively enrolled patients with a diagnosis of PMR referred to our center during the previous year for respiratory symptoms. Data concerning clinical and serological manifestations suggesting Connective Tissue Disease (CTD), High-Resolution Chest Tomography (HRCT), and Pulmonary Function Tests (PFTs) were systematically collected in order to verify the diagnosis. RESULTS: Fifteen out of seventeen PMR patients had ILD. Ten patients had a confirmed diagnosis of PMR, while in five patients a CTD was discovered. Seven patients showed a severe restrictive pattern at PFTs requiring oxygen supplementation (five with PMR and two with CTD). In thirteen patients pulmonary symptoms started before or together with muscular symptoms. Regarding HRCT patterns, patients showed a Nonspecific Interstitial Pneumonia in nine cases, Usual Interstitial Pneumonia (UIP) and possible UIP in two and three cases, and a single case of Organizing Pneumonia and Combined Pulmonary Fibrosis and Emphysema Syndrome. CONCLUSIONS: Lung involvement should be evaluated in PMR patients, especially if asthenia is poorly responsive to low doses of steroids. In these cases, the diagnosis should be re-evaluated in depth, looking for a seronegative Rheumatoid Arthritis, a clinically amyopathic myositis or Interstitial Pneumonia with Autoimmune features.

Regional grafting of autologous adipose tissue is effective in inducing prompt healing of indolent digital ulcers in patients with systemic sclerosis: results of a monocentric randomized controlled study.

BACKGROUND: A randomized controlled trial (RCT) was performed to confirm preliminary uncontrolled data indicating that regional adipose tissue (AT) grafting (G) is effective in inducing ischemic digital ulcer (IDU) healing in patients with systemic sclerosis (SSc). PATIENTS AND METHODS: SSc patients with IDUs were randomized to be blindly treated with AT-G or a sham procedure (SP). AT-G consisted of injection, at the base of the finger with the IDU, of 0.5-1 ml AT after centrifugation of fat aspirate. The SP consisted of false liposuction and local injection of saline solution. The primary endpoint was to compare the cumulative prevalence of healed IDUs in the two groups within the following 8 weeks. RESULTS: AT-G and the SP were carried out in 25 and 13 patients, respectively. The two groups were comparable for age, gender, disease duration, and SSc subtypes. IDU healing was observed in 23/25 and 1/13 patients treated with AT-G and the SP, respectively (p < 0.0001). The 12 patients who received the unsuccessful SP underwent a rescue AT-G. In all of them, IDU healing was observed after 8 weeks of observation. It was noticeable that in the AT-G-treated patients a significant reduction of pain intensity (measured by visual analogue scale) was recorded after 4 and 8 weeks (p < 0.0001 in all cases). Similarly, a significant increase of capillary numbers in the affected finger was recorded by nailfold videocapillaroscopy after 4 and 8 weeks (p < 0.0001 in both cases). CONCLUSION: This RCT strongly confirms that AT-G is effective in inducing IDU healing in SSc patients. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03406988 . Registered retrospectively on 25 January 2018.

NEMO score in nailfold videocapillaroscopy is a good tool to assess both steady state levels and overtime changes of disease activity in patients with systemic sclerosis: a comparison with the proposed composite indices for this disease status entity.

BACKGROUND: In previous studies, we demonstrated that the NEMO score, i.e. the cumulative number of microhaemorrhages (MHEs) and microthromboses (MTs), observed in nailfold videocapillaroscopy was a good indicator of the steady state level of disease activity (DA) in patients with systemic sclerosis (SSc) when the European Scleroderma Study Group (EScSG) index was considered the gold standard. AIM OF THE STUDY: To verify whether the NEMO score could be (i) a valid tool to assess DA, even when the modified European Scleroderma Trials and Research (EUSTAR) index was considered to be the comparator, and (ii) a sensitive method to capture the DA overtime changes. PATIENTS AND METHODS: The NEMO score and the EScSG and EUSTAR indices were contemporarily assessed at baseline (T0) and after a follow-up of 4-56 months (T1) in 98 patients with SSc. The differences (Δ) between the T1 and T0 values of the NEMO score and the EScSG and EUSTAR indices were calculated and compared to each other. RESULTS: NEMO score values were very closely correlated with the corresponding values of the EScSG and EUSTAR indices both at T0 and T1 observations (p < 0.0001 in all cases with the exception of the correlation with EScSG values at T1 (p < 0.03)). The values of the two composite DA indices were also strictly related to each other in both T0 and T1 observations (p < 0.0001). Receiver operating characteristic (ROC) curve analysis showed the NEMO score had a good sensitivity and specificity in classifying patients with a predefined level of DA (scores ≥ 3.0 and ≥ 2.5 for the EScSG and EUSTAR indices, respectively, p < 0.0001 in both cases). Δ values of the NEMO score were significantly correlated with the corresponding values of both the EScSG and EUSTAR indices. Weighted Cohen's k level of agreement between Δ values of the NEMO score and those of the EScSG and EUSTAR indices was moderate (0.55 and 0.59, respectively). CONCLUSIONS: NEMO score proves to be a feasible, non-invasive, and valid tool to assess steady state levels and changes over time of DA in patients with SSc. Thus, it can represent an alternative or complementary method to measure this disease status entity in this disorder.

Gene Expression Profiles in Primary Sjögren's Syndrome With and Without Systemic Manifestations.

OBJECTIVE: To investigate the gene expression profile in patients with Sjögren's syndrome that is characterized by different clinical phenotypes. METHODS: RNA from peripheral blood mononuclear cells was purified in 8 patients with glandular features (GFs) and widespread pain (WP) and 11 with extraglandular manifestations (EGMs) and then was analyzed by hybridization on a human gene chip exploring more than 40,000 human genes. Differentially expressed genes (DEGs) in the two subgroups (ie, those with false discovery rate-corrected P values ≤ 0.01) with respect to 20 healthy controls have been submitted to functional classification using a Gene Ontology database and were mapped to define the networks of protein to protein interactions (PPIs). RESULTS: The enriched pathway analyses of DEGs and of the highly interconnected modules identified in the PPI networks showed that the pathological processes characterizing the two subgroups were substantially different. The predominant pathways in patients with EGMs are related to T- and B-cell activation, Toll-like receptor, interferon signaling, and apoptosis. Conversely, pathological processes related to pain transmission and modulation are preferentially operative in patients with GFs and WP. These data suggest that a neuroinflammatory pathway driven by cytokines and chemokines may play a central role in triggering WP features in this phenotype of patients. CONCLUSION: The present study supports the hypothesis that different biological pathways are operative in patients with primary Sjögren's syndrome with different clinical phenotypes. A better knowledge of these specific processes might help in tailoring more effective target therapies.

Clinical, serological and radiological features of a prospective cohort of Interstitial Pneumonia with Autoimmune Features (IPAF) patients.

BACKGROUND: The term Interstitial Pneumonia with Autoimmune Features (IPAF) describes patients with Interstitial Lung Diseases (ILDs) and clinical or serological features of autoimmune diseases insufficient to reach a specific classification of a Connective Tissue Disease (CTD). Currently, retrospective studies on IPAF patients have proven to be heterogeneous in general characteristics, outcomes and High-Resolution Computed Tomography (HRCT) pattern. This study aims to describe for the first time the clinical, serological and radiological features of a prospective cohort of IPAF patients. This cohort is then compared to a group of patients with Idiopathic Pulmonary Fibrosis (IPF). MATERIAL AND METHODS: From 626 consecutive ILD patients evaluated, 45 IPAF and a comparison cohort of 143 IPF patients were enrolled. All patients underwent clinical assessment with rheumatologic and respiratory evaluation, HRCT, Pulmonary Function Tests and Nailfold Videocapillaroscopy. RESULTS: The IPAF patients had a predominance of female gender (62.12%) with a median age of 66 years. The most common findings were: Nonspecific Interstitial Pneumonia (NSIP, 68.89%), Antinuclear Antibody positivity (17.77%) and Raynaud Phenomenon (31.11%). In comparison with IPF, IPAF patients showed younger age, better performances in Pulmonary Function Tests, less necessity of O2 support and predominance of female sex and NSIP pattern. DISCUSSION: This is the first report of a prospective cohort of IPAF patients. IPAF patients seem to have a less severe lung disease than IPF. IPAF criteria probably need to be revisited and validated, but their capacity to recruit patients with incomplete forms or early onset of CTD could be useful for further research.

The Role of Endothelial Progenitors in the Repair of Vascular Damage in Systemic Sclerosis.

Systemic sclerosis (SSc) is a connective tissue disease characterized by a complex pathological process where the main scenario is represented by progressive loss of microvascular bed, with the consequent progressive fibrotic changes in involved organ and tissues. Although most aspects of vascular injury in scleroderma are poorly understood, recent data suggest that the scleroderma impairment of neovascularization could be related to both angiogenesis and vasculogenesis failure. Particularly, compensatory angiogenesis does not occur normally in spite of an important increase in many angiogenic factors either in SSc skin or serum. Besides insufficient angiogenesis, the contribution of defective vasculogenesis to SSc vasculopathy has been extensively studied. Over the last decades, our understanding of the processes responsible for the formation of new vessels after tissue ischemia has increased. In the past, adult neovascularization was thought to depend mainly on angiogenesis (a process by which new vessels are formed by the proliferation and migration of mature endothelial cells). More recently, increased evidence suggests that stem cells mobilize from the bone marrow into the peripheral blood (PB), differentiate in circulating endothelial progenitors (EPCs), and home to site of ischemia to contribute to de novo vessel formation. Significant advances have been made in understanding the biology of EPCs, and molecular mechanisms regulating EPC function. Autologous EPCs now are becoming a novel treatment option for therapeutic vascularization and vascular repair, mainly in ischemic diseases. However, different diseases, such as cardiovascular diseases, diabetes, and peripheral artery ischemia are related to EPC dysfunction. Several studies have shown that EPCs can be detected in the PB of patients with SSc and are impaired in their function. Based on an online literature search (PubMed, EMBASE, and Web of Science, last updated December 2017) using keywords related to "endothelial progenitor cells" and "Systemic Sclerosis," "scleroderma vasculopathy," "angiogenesis," "vasculogenesis," this review gives an overview on the large body of data of current research in this issue, including controversies over the identity and functions of EPCs, their meaning as biomarker of SSc microangiopathy and their clinical potency.