Mesoglycan: Clinical Evidences for Use in Vascular Diseases

Vascular glycosaminoglycans (GAG) are essential components of the endothelium and vessel wall and have been shown to be involved in several biologic functions. Mesoglycan, a natural GAG preparation, is a polysaccharide complex rich in sulphur radicals with strong negative electric charge. It is extracted from porcine intestinal mucosa and is composed of heparan sulfate, dermatan sulfate, electrophoretically slow-moving heparin, and variable and minimal quantities of chondroitin sulfate. Data on antithrombotic and profibrinolytic activities of the drug show that mesoglycan, although not indicated in the treatment of acute arterial or venous thrombosis because of the low antithrombotic effect, may be useful in the management of vascular diseases, when combined with antithrombotics in the case of disease of cerebral vasculature, and with antithrombotics and vasodilator drugs in the case of chronic peripheral arterial disease. The protective effect of mesoglycan in patients with venous thrombosis and the absence of side effects, support the use of GAG in patients with chronic venous insufficiency and persistent venous ulcers, in association with compression therapy (zinc bandages, multiple layer bandages, etc.), elastic compression stockings, and local care, and in the prevention of recurrences in patients with previous DVT following the standard course of oral anticoagulation treatment

Unilateral Post-Chemotherapy Robot-Assisted Retroperitoneal Lymph Node Dissection for Stage II Non-Seminomatous Germ Cell Tumors: Sexual and Reproductive Outcomes

: We aimed to report sexual and reproductive outcomes following post-chemotherapy robot-assisted retroperitoneal unilateral lymph node dissection (PC-rRPLND) for non-seminomatous germ cell tumors (NSGCTs) at a high-volume cancer center. We collected records regarding sexual and reproductive outcomes of patients undergoing unilateral PC-rRPLND for stage II NSGCTs from January 2018 to November 2021. Preoperative and postoperative (at 12 months) ejaculatory function as well as erectile function, based on the International Index of Erectile Function-5 (IIEF-5) and Erection Hardness Score (EHS), were assessed. Only patients with a pre-operative IIEF-5 of ≥22 and EHS of ≥3 were included in this analysis. Overall, 22 patients undergoing unilateral PC-rRPLND met the inclusion criteria. Of these, seven (31.8%) patients presented an andrological disorder of any type after PC-rRPLND. Specifically, retrograde ejaculation was present in three (13.6%) patients and hypospermia was present in one (4.5%) patient. Moreover, three (13.6%) patients yielded erectile dysfunction (IIEF-5 < 22 and/or EHS < 3). Lastly, two (9.1%) succeeded in naturally conceiving a child after PC-rRPLND. Retrograde ejaculation is confirmed to be one of the most common complications of PC-rRPLND. Moreover, a non-negligible number of patients experience erectile dysfunction

The Italian Draft Law on the \u2018Provisions Concerning the Safeguarding of the Intangible Cultural Heritage\u2019

Intangible cultural heritage in Italy is still in need of a unified approach, capable of providing reliable criteria for identifying its assets and for indicating timescales and means by which they should be safeguarded. In the continued absence of up-to-date, ad hoc state legislation (since the content of those laws which do implement international Conventions is too generic in nature to be sufficiently effective), the Regions have proceeded to act in a somewhat scattered manner, giving rise to an extremely fragmented and very disorderly regulatory framework. The draft law N. 4486, "Provisions Concerning the Safeguarding of the Intangible Cultural Heritage", presented on 12th May 2017 at the Chamber of Deputies of the Italian Republic - as the result of the work of an interdisciplinary and inter-university research team coordinated by Marco Giampieretti, who has drafted the final text with the collaboration of Simona Pinton - seeks to fill the serious void that exists in Italian legal system by aligning it to the principles of international and European law, by redirecting the relevant State and Regional legislation, and by satisfying the fundamental requirements of the national community

Treatment of hemophilia: a review of current advances and ongoing issues

Replacement of the congenitally deficient factor VIII or IX through plasma-derived or recombinant concentrates is the mainstay of treatment for hemophilia. Concentrate infusions when hemorrhages occur typically in joint and muscles (on-demand treatment) is able to resolve bleeding, but does not prevent the progressive joint deterioration leading to crippling hemophilic arthropathy. Therefore, primary prophylaxis, ie, regular infusion of concentrates started after the first joint bleed and/or before the age of two years, is now recognized as first-line treatment in children with severe hemophilia. Secondary prophylaxis, whenever started, aims to avoid (or delay) the progression of arthropathy and improve patient quality of life. Interestingly, recent data suggest a role for early prophylaxis also in preventing development of inhibitors, the most serious complication of treatment in hemophilia, in which multiple genetic and environmental factors may be involved. Treatment of bleeds in patients with inhibitors requires bypassing agents (activated prothrombin complex concentrates, recombinant factor VIIa). However, eradication of inhibitors by induction of immune tolerance should be the first choice for patients with recent onset inhibitors. The wide availability of safe factor concentrates and programs for comprehensive care has now resulted in highly satisfactory treatment of hemophilia patients in developed countries. Unfortunately, this is not true for more than two-thirds of persons with hemophilia, who live in developing countries

Perioperative outcomes of patients undergoing urological elective surgery during the covid-19 pandemic: A national overview across 28 italian institutions

Introduction: The aim of this study was to assess the safety of elective urological surgery performed during the pandemic by estimating the prevalence of COVID-19-like symptoms in the postoperative period and its correlation with perioperative and clinical factors. Material and methods: In this multicenter, observational study we recorded clinical, surgical and postoperative data of consecutive patients undergoing elective urological surgery in 28 different institutions across Italy during initial stage of the COVID-19 pandemic (between February 24 and March 30, 2020, inclusive). Results: A total of 1943 patients were enrolled. In 12%, 7.1%, 21.3%, 56.7% and 2.6% of cases an open, laparoscopic, robotic, endoscopic or percutaneous surgical approach was performed, respectively. Overall, 166 (8.5%) postoperative complications were registered, 77 (3.9%) surgical and 89 (4.6%) medical. Twenty-eight (1.4%) patients were readmitted to hospital after discharge and 13 (0.7%) died. In the 30 days following discharge, fever and respiratory symptoms were recorded in 101 (5.2%) and 60 (3.1%) patients. At multivariable analysis, not performing nasopharyngeal swab at hospital admission (HR 2.3; CI 95% 1.01-5.19; p = 0.04) was independently associated with risk of developing postoperative medical complications. Number of patients in the facility was confirmed as an independent predictor of experiencing postoperative respiratory symptoms (p = 0.047, HR:1.12; CI95% 1.00-1.05), while COVID-19-free type of hospitalization facility was a strong independent protective factor (p = 0.02, HR:0.23, CI95% 0.07-0.79). Conclusions: Performing elective surgery during the COVID-19 pandemic does not seem to affect perioperative outcomes as long as proper preventive measures are adopted, including nasopharyngeal swab before hospital admission and hospitalization in dedicated COVID-19-free facilities

Rate and predictors of thromboprophylaxis in internal medicine wards: Results from the AURELIO study

Background: Randomized controlled trials suggest that prophylactic doses of anticoagulants effectively prevent venous thromboembolism (VTE) in hospitalized medical patients with high thromboembolic risk. However, no prospective studies exist regarding the real-world prevalence of prophylactic anticoagulant use. This prospective study aimed to determine the rate and predictors of thromboprophylaxis in an unselected population of patients hospitalized in medical departments. Methods: We conducted a multicenter prospective observational study (AURELIO - rAte of venous thrombosis in acutely iLl patIents hOspitalized) to assess the rate of deep vein thrombosis (DVT) in unselected acutely ill patients hospitalized in medical wards using compression ultrasound (CUS) at admission and discharge. Additionally, we evaluated the rate of pharmacological thromboprophylaxis administration in this population and analyzed the thrombotic risk by assessing RAMs (Risk Assessment Models) such as the IMPROVE-VTE and PADUA scores following the clinician's decision to administer thromboprophylaxis. Patients with IMPROVE-VTE scores ≥3 and/or PADUA scores ≥4 were classified as high thrombotic risk; those with IMPROVE-VTE scores &lt;3 and/or PADUA scores &lt;4 were classified as low risk. Results: We recruited 2371 patients (1233 males [52&nbsp;%] and 1138 females [48&nbsp;%]; mean age 72&nbsp;±&nbsp;16&nbsp;years). The median length of hospitalization was 13&nbsp;±&nbsp;12&nbsp;days. Overall, 442/2371 (18.6&nbsp;%) patients received prophylactic parenteral anticoagulants (subcutaneous low weight molecular heparin or fondaparinux once daily) at admission. Assessing the thrombotic risk of the population recruited 1016 (42.9&nbsp;%) patients were classified as high risk and 1354 (57.1&nbsp;%) were low risk. Among high-risk patients, 339/1016 (33.4&nbsp;%) received anticoagulant prophylaxis compared to 103/1354 (7.6&nbsp;%) low-risk patients. During hospitalization, 9 patients developed DVT, comprising 7 asymptomatic and 2 symptomatic cases of proximal DVT. Of these, 3 patients were on anticoagulant prophylaxis, while 6 were not. Among the high-risk population, 7 out of 1016 patients (0.7&nbsp;%) experienced proximal DVT during hospitalization, with 2 out of these 7 (28&nbsp;%) receiving anticoagulant thromboprophylaxis. In the low-risk population, 2 out of 1354 patients (0.2&nbsp;%) developed DVT, with 1 out of these 2 (50&nbsp;%) receiving anticoagulant thromboprophylaxis. Age, heart or respiratory failure, pneumonia, active neoplasia, previous VTE, reduced mobility, and absence of kidney failure were more frequent in patients receiving prophylaxis. Multivariable logistic regression identified age (RR 1.010; CI 95&nbsp;% 1002-1019; p&nbsp;=&nbsp;0.015), heart/respiratory failure (RR 1.609; CI 95&nbsp;% 1248-2075; p&nbsp;&lt;&nbsp;0.0001), active neoplasia (RR 2.041; CI 95&nbsp;% 1222-2141; p&nbsp;&lt;&nbsp;0.0001), pneumonia (RR 1.618; CI 95&nbsp;% 1557-2676; p&nbsp;&lt;&nbsp;0.0001), previous VTE (RR 1.954; CI 95&nbsp;% 1222-3125; p&nbsp;&lt;&nbsp;0.0001), and reduced mobility (RR 4.674; CI 95&nbsp;% 3700-5905; p&nbsp;&lt;&nbsp;0.0001) as independent predictors of thromboprophylaxis. Conclusions: This study, conducted without pre-established thromboembolic risk scores, offers a comprehensive view of venous thromboembolism prophylaxis in medical patients with acute conditions hospitalized in internal medicine departments. It reveals that advanced age, heart or respiratory failure, active cancer, pneumonia, previous VTE, and reduced mobility are predictors that may influence the decision to administer thromboprophylaxis in these patients

Neutrophil-lymphocyte ratio is associated with worse outcomes in patients with cirrhosis: insights from the PRO-LIVER Registry

Background: Liver cirrhosis (LC) is a leading global cause of morbidity and mortality, with inflammation playing a key role in disease progression and clinical complications of LC. The Neutrophil/Lymphocyte Ratio (NLR), a readily available marker of systemic inflammation, has been linked to short-term adverse outcomes in LC, but data on long-term follow-up are limited. This study aimed to investigate the relationship between NLR and long-term all-cause mortality in an unselected cohort of LC patients. Methods: Data were gathered from the Italian multicenter observational study "PRO-LIVER". Patients with available data to calculate NLR at baseline were included. Baseline clinical determinants of NLR and the association of NRL with all-cause mortality at 2-year follow-up were evaluated. Results: From the overall cohort (n = 753), 506 patients with LC (31% female, mean age 64.8 ± 11.9 years) were included in the analysis. Median value of NLR was 2.42 (Interquartile Range [IQR]: 1.61-3.52). At baseline, patients with NLR ≥ 2.42 were more likely to have Child-Pugh B or C, hepatocellular carcinoma (HCC), or portal vein thrombosis (PVT). After a median follow-up of 21 months, 129 patients died: 44 (17%) with NLR &lt; 2.42 and 85 (34%) with NLR ≥ 2.42 (p &lt; 0.001). At multiple-adjusted Cox regression analysis, NLR ≥ 2.42 was independently associated with all-cause mortality (HR: 1.65; 95% CI: 1.12-2.44; p = 0.012), along with age, Child-Pugh C class, HCC and PVT. Conclusions: NLR is associated with long-term all-cause mortality in LC. NLR may serve as a potentially easily available tool to aid risk refinement in LC

Serum Albumin Is Inversely Associated With Portal Vein Thrombosis in Cirrhosis

We analyzed whether serum albumin is independently associated with portal vein thrombosis (PVT) in liver cirrhosis (LC) and if a biologic plausibility exists. This study was divided into three parts. In part 1 (retrospective analysis), 753 consecutive patients with LC with ultrasound-detected PVT were retrospectively analyzed. In part 2, 112 patients with LC and 56 matched controls were entered in the cross-sectional study. In part 3, 5 patients with cirrhosis were entered in the in vivo study and 4 healthy subjects (HSs) were entered in the in vitro study to explore if albumin may affect platelet activation by modulating oxidative stress. In the 753 patients with LC, the prevalence of PVT was 16.7%; logistic analysis showed that only age (odds ratio [OR], 1.024; P = 0.012) and serum albumin (OR, -0.422; P = 0.0001) significantly predicted patients with PVT. Analyzing the 112 patients with LC and controls, soluble clusters of differentiation (CD)40-ligand (P = 0.0238), soluble Nox2-derived peptide (sNox2-dp; P &lt; 0.0001), and urinary excretion of isoprostanes (P = 0.0078) were higher in patients with LC. In LC, albumin was correlated with sCD4OL (Spearman's rank correlation coefficient [r(s)], -0.33; P &lt; 0.001), sNox2-dp (r(s), -0.57; P &lt; 0.0001), and urinary excretion of isoprostanes (r(s), -0.48; P &lt; 0.0001) levels. The in vivo study showed a progressive decrease in platelet aggregation, sNox2-dp, and urinary 8-iso prostaglandin F2 alpha-III formation 2 hours and 3 days after albumin infusion. Finally, platelet aggregation, sNox2-dp, and isoprostane formation significantly decreased in platelets from HSs incubated with scalar concentrations of albumin. Conclusion: Low serum albumin in LC is associated with PVT, suggesting that albumin could be a modulator of the hemostatic system through interference with mechanisms regulating platelet activation

Use of heparin preparations in older patients

Thrombotic events are a major cause of morbidity in the elderly and are a growing concern in the medical community as the population ages. A shift to a procoagulant state occurs with aging, and aging itself is a risk factor for arterial and venous thrombosis. Unfractionated heparin (UFH) is a heterogeneous mixture of glycosaminoglycans that binds to antithrombin via a pentasaccharide, and catalyzes the inactivation of thrombin and other clotting factors. Different factors affect drug levels and drug sensitivity in older people. Alteration in drug kinetics and toxicity, coagulation factors, and changes in body composition as well as weight due to aging can affect anticoagulant therapy. A careful evaluation of renal function and poly-pharmacotherapy appears to be mandatory before therapy with LMWH is started in older patients. UFH and low molecular weight heparin(LMWH) are as effective in older individuals as in younger ones to prevent and treat thrombosis. However, they are associated with a higher risk of bleeding in older individuals, especially in those with kidney insufficiency. © 2005 Copyright © 2005 Elsevier B.V. All rights reserved.