CORRELATION BETWEEN NAILFOLD VIDEOCAPILLAROSCOPY PATTERNS, LEFT VENTRICLE DYSFUNCTION AND PULMONARY DISEASE IN SYSTEMIC SCLEROSIS,

Background: Systemic Sclerosis (SSc) is a multisystem connective disease characterized by a microvascular damage, which leads to systemic fibrosis, immune dysregulation and progressive involvement of internal organs [1]. According to the classification of the morphological aspects, into the scleroderma pattern proposed by Cutolo et al. are described the early, active and late patterns. Objectives: The aim of our study is thus to report a correlation between specific nailfold videocapillaroscopy pattern and internal organ involvement. Methods: All enrolled patients were diagnosed for SSc, according to the American College of Rheumatology criteria and underwent an echocardiographic examination and a nailfold videocapillaroscopy. Myocardial function parameters considered were: global contractility (computed with the Simpson method), linear contractility (computed through the MAPSE) [2], diastolic dysfunction (through the analysis of the trans-mitral flow) [3]; whilst those of lung damage were: PAPs and the evaluation of the right ventricle contractility through the TAPSE [4]. Statistics were performed with SPSS 20 software, by using the Mann Whitney U Test and the Fisher Test. Results: We enrolled 27 patients, of which 16 showing “active pattern” and 11 “early pattern”, compared to a group of 21 healthy controls. Of the 11 patients belonging to the “early” group, 1 resulted affected by diastolic dysfunction, whilst 3 had pulmonary hypertension, defined by PAPs ≥40 mmHg [4] (early vs controls; p=0.03). In the 16 patients of the “active” group. instead, 5 were found to have a diastolic dysfunction (active vs controls; p=0.01) and 6 pulmonary hypertension (active vs controls; p=0.003). In the group with “active” pattern we also observed a reduction in TAPSE compared to the control group (2,0 ± 0,2 vs 2,2 ± 0,2; p=0,025) and compared to the group with early pattern (2,0 ± 0,2 vs 2,2 ± 0,3; p=0,07). No presence of modifications in the global contractility emerged; however, we observed a progressive reduction of the MAPSE (controls 1.76 ± 0,08; early 1.57 ± 0,04; active 1.49 ± 0,12), which resulted statistically significant among the different comparisons (controls vs early p=0.001; controls vs active p=0.0001; early vs active p=0.04). Conclusion: The analyses showed a strict correlation between the severity of the microvascoular alterations, reported by nailfold videocapilloroscopy, and the severity of the cardiopulmonary damage, expressed by an increase in the percentage of pulmonary hypertension, diastolic dysfunction and a progressive reduction of MAPSE and TAPSE. Abstract AB1155 Table 1 early vs controls EARLY CONTROLS P PAPs 32,3 ± 5,4 22,6 ± 6,7 0,0001 TAPSE 2,2 ± 0,3 2,2 ± 0,2 NS MAPSE 1,57 ± 0,04 1,76 ± 0,08 0,0001 EF 65 ± 4 64 ± 2,7 NS E/A 1,34 ± 0,2 1,38 ± 0,19 NS DECT 148 ± 23 163 ± 27 NS Diastolic dysfunction 1(11) 0(21) 0,3 Pulmonary hypertension 3(11) 0(21) 0,03 Abstract AB1155 Table 2 active vs controls ACTIVE CONTROLS P PAPs 34 ± 7,8 22,6 ± 6,7 0,0001 TAPSE 2,0 ± 0,2 2,2 ± 0,2 0,025 MAPSE 1,49 ± 0,12 1,76 ± 0,08 0,0001 EF 65 ± 4 64 ± 2,7 NS E/A 1,34 ± 0,4 1,38 ± 0,19 NS DECT 157 ± 24 163 ± 27 NS Diastolic dysfunction 5(16) 0(21) 0,01 Pulmonary hypertension 6(16) 0(21) 0,003 REFERENCES: [1] LeRoy EC. Systemic sclerosis. A vascular perspective. Rheum Dis Clin North Am. [2] Ibadete Bytci, Left atrial change in early stages of heart failure with preserved ejection fraction. Echocardiography [3] Sherif F. Recommendations for the Evaluation of Left Ventricular Diastolic Function by Echocardiography. Journal of the American Society of Echocardiography [4] Luke S. Howard, Echocardiographic assessment of pulmonary hypertension: standard operating procedure. European Respiratory Revie

Metformin: A Potential Therapeutic Tool for Rheumatologists

Metformin is an oral antihyperglycemic drug widely used to treat type 2 diabetes, acting via indirect activation of 5′ Adenosine Monophosphate-activated Protein Kinase (AMPK). Actually, evidence has accumulated of an intriguing anti-inflammatory activity, mainly mediated by AMPK through a variety of mechanisms such as the inhibition of cytokine-stimulated Nuclear Factor-κB (NF-κB) and the downregulation of the Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) signaling pathways. Moreover, AMPK plays an important role in the modulation of T lymphocytes and other pivotal cells of the innate immune system. The current understanding of these AMPK effects provides a strong rationale for metformin repurposing in the management of autoimmune and inflammatory conditions. Several studies demonstrated metformin’s beneficial effects on both animal and human rheumatologic diseases, especially on rheumatoid arthritis. Unfortunately, even though data are large and remarkable, they almost exclusively come from experimental investigations with only a few from clinical trials. The lack of support from prospective placebo-controlled trials does not allow metformin to enter the therapeutic repertoire of rheumatologists. However, a large proportion of rheumatologic patients can currently benefit from metformin, such as those with concomitant obesity and type 2 diabetes, two conditions strongly associated with rheumatoid arthritis, osteoarthritis, and gout, as well as those with diabetes secondary to steroid therapy

Coronary Microvascular Dysfunction in Diabetes Mellitus: Pathogenetic Mechanisms and Potential Therapeutic Options

Diabetic patients are frequently affected by coronary microvascular dysfunction (CMD), a condition consisting of a combination of altered vasomotion and long-term structural change to coronary arterioles leading to impaired regulation of blood flow in response to changing cardiomyocyte oxygen requirements. The pathogenesis of this microvascular complication is complex and not completely known, involving several alterations among which hyperglycemia and insulin resistance play particularly central roles leading to oxidative stress, inflammatory activation and altered barrier function of endothelium. CMD significantly contributes to cardiac events such as angina or infarction without obstructive coronary artery disease, as well as heart failure, especially the phenotype associated with preserved ejection fraction, which greatly impact cardiovascular (CV) prognosis. To date, no treatments specifically target this vascular damage, but recent experimental studies and some clinical investigations have produced data in favor of potential beneficial effects on coronary micro vessels caused by two classes of glucose-lowering drugs: glucagon-like peptide 1 (GLP-1)-based therapy and inhibitors of sodium-glucose cotransporter-2 (SGLT2). The purpose of this review is to describe pathophysiological mechanisms, clinical manifestations of CMD with particular reference to diabetes, and to summarize the protective effects of antidiabetic drugs on the myocardial microvascular compartment

Remdesivir plus dexamethasone versus dexamethasone alone for the treatment of COVID-19 patients requiring supplemental O2 therapy: a prospective controlled non-randomized study

Background: Remdesivir is an antiviral used to treat COVID-19 which improves some clinical outcomes. Dexamethasone has been shown to be effective in reducing mortality. It has been hypothesized that combination of these two drugs can improve mortality. We evaluated the effect of combination on mortality of COVID-19 patients requiring O2 therapy. Methods: A prospective quasi-experimental study, including two independent, sequential controlled cohorts, one received remdesivir-dexamethasone and the other dexamethasone alone, was designed. All COVID-19 patients requiring supplemental O2 therapy were enrolled consecutively. The sample size to power mortality was a priori calculated. The primary endpoints were 30-day mortality and viral clearance differences. Secondary endpoints were differences in hospitalization times, improvement in respiratory failure (PO2/FiO2) and inflammatory indices (fibrinogen, CRP, neutrophil/lymphocyte ratio, D-Dimer). Kaplan-Meier curves and the log-rank test were used to evaluate significant differences in mortality between groups. Results: 151 COVID-19 patients were enrolled (remdesivir/dexamethasone group, 76 and dexamethasone alone,75). No differences in demographic, clinical and laboratory characteristics were observed between the two groups at baseline. Faster viral clearance occurred in the remdesivir/dexamethasone group compared to dexamethasone alone (median 6 vs 16 days; p<0.001). 30-days mortality in the remdesivir/dexamethasone group was 1.3%, while in dexamethasone alone was 16% (p<0.005). In the remdesivir/dexamethasone group compared to dexamethasone alone there was a reduction in hospitalization days (p<0.0001) and a faster improvement in both respiratory function and inflammatory markers. Conclusions: Remdesivir/dexamethasone treatment is associated with significant reduction in mortality, length of hospitalization, and faster SARS-CoV-2 clearance, compared to dexamethasone alone

Gender Differences in the Pathogenesis and Risk Factors of Hepatocellular Carcinoma

Simple Summary Significant gender disparities have been highlighted in the incidence, aggressiveness, and prognosis of HCC. A different epidemiological distribution of the risk factors of liver damage and, above all, the actions of sex hormones are at the basis of these differences. Accurate knowledge of gender disparities in HCC would lead to adequate surveillance strategies and the potential implementation of current treatment schemes. Several chronic liver diseases are characterized by a clear gender disparity. Among them, hepatocellular carcinoma (HCC) shows significantly higher incidence rates in men than in women. The different epidemiological distribution of risk factors for liver disease and HCC only partially accounts for these gender differences. In fact, the liver is an organ with recognized sexual dysmorphism and is extremely sensitive to the action of androgens and estrogens. Sex hormones act by modulating the risk of developing HCC and influencing its aggressiveness, response to treatments, and prognosis. Furthermore, androgens and estrogens are able to modulate the action of other factors and cofactors of liver damage (e.g., chronic HBV infection, obesity), significantly influencing their carcinogenic power. The purpose of this review is to examine the factors related to the different gender distribution in the incidence of HCC as well as the pathophysiological mechanisms involved, with particular reference to the central role played by sex hormones