Biomarkers in post-reperfusion syndrome after acute lower limb ischaemia

Ischaemia reperfusion (I/R) injury refers to tissue damage caused when blood supply returns to the tissue after a period of ischaemia. Matrix metalloproteinases (MMPs), neutrophil gelatinase-associated lipocalin (NGAL) and cytokines are biomarkers involved in several vascular complications. The aim of this study was to evaluate the role of MMPs, NGAL and inflammatory cytokines in I/R syndrome. We conducted an open label, multicentric, parallel group study, between January 2010 and December 2013. Patients with acute limb ischaemia were enrolled in this study and were divided into two groups: (i) those subjected to fasciotomy and (ii) those not subjected to fasciotomy, according to the onset of compartment syndrome. Plasma and tissue values of MMPs and NGAL as well as plasma cytokines were evaluated. MMPs, NGAL and cytokine levels were higher in patients with compartment syndrome. Biomarkers evaluated in this study may be used in the future as predictors of I/R injury severity and its possible evolution towards post-reperfusion syndrome

Prosthetic replacement of the infrahepatic inferior vena cava for leiomyosarcoma.

HYPOTHESIS: Resection of the infrahepatic inferior vena cava associated with prosthetic graft replacement for caval leiomyosarcoma is an acceptable procedure to obtain prolonged and good-quality survival. DESIGN: A consecutive sample clinical study with a mean follow-up of 40 months. SETTING: The surgical department of an academic tertiary center and an affiliated secondary care center. PATIENTS: Eleven patients, with a mean age of 51 years, who have primary leiomyosarcoma of the infrahepatic inferior vena cava. INTERVENTIONS: All of the patients underwent radical resection of the tumor en bloc with the affected segment of the vena cava. Reconstruction consisted of 10 cavocaval polytetrafluoroethylene grafts and 1 cavobiliac graft. An associated right nephrectomy was performed in 2 cases. The left renal vein was reimplanted in the graft in 3 cases. MAIN OUTCOME MEASURES: Cumulative disease-specific survival, disease-free survival, and graft patency rates expressed by standard life-table analysis. RESULTS: No patients died in the postoperative period. The cumulative (SE) disease-specific survival rate was 53% (21%) at 5 years. The cumulative (SE) disease-free survival rate was 44% (19%) at 5 years. The cumulative (SE) graft patency rate was 67% (22%) at 5 years. CONCLUSION: Radical resection followed by prosthetic graft reconstruction is a valuable method for treating primary leiomyosarcoma of the infrahepatic inferior vena cava

Carotid body paragangliomas and Matrix Metalloproteinases.

Background: The carotid body tumors (CBTs) are relatively rare neoplasms and may present into benign or life threatening malignant forms. Matrix metalloproteinases (MMPs) are often involved in vascular and cancer diseases. Objective of this study is to study the relationship between CBTs and MMPs. Methods: We performed a multicenter study on 14 patients with CBTs. All tumors were resected. For each patient, we evaluated the MMPs’ levels in both plasma (enzyme-linked immunosorbent assay [ELISA] test) and tissue samples (Western blot analysis). These MMPs’ plasma levels were compared with the MMPs’ plasma levels of healthy patients. Results: Eleven patients had benign CBTs, whereas 3 patients had malignant CBTs. ELISA findings revealed significant higher levels (P < 0.01) of MMP-1, -2, -3, -8, and -9 in patients with paraganglioma with respect to healthy patients. Patients with malignant CBTs showed significantly higher levels (P < 0.01) of MMP-1, -2, and -3 compared with patients with benign CBTs. Conclusions: Because this is an exploratory study, the experience on this casuistry showed that MMPs’ evaluation may help clinicians and surgeons to formulate a more rapid and clear diagnosis on CBTs’ behavior. However, other studies on a large group of patients may be useful to validate these observations

The role of matrix metalloproteinases and neutrophil gelatinase-associated lipocalin in central and peripheral arterial aneurysms

Introduction. An association between arterial aneurysms and matrix metalloproteinases (MMPs) has been described previously. MMPs regulate extracellular structural proteins and tissue remodeling. Neutrophil gelatinase-associated lipocalin (NGAL) is involved in the regulation ofMMPactivity. The aim of this work was to study the relationship between the levels of MMPs and NGAL and arterial aneurysms. Methods. In a multicenter, open-label, parallel groups, prospective study, patients with aneurysmal disease were divided into 2 groups: Group I (with ruptured aneurysm) and group II (with nonruptured aneurysm). Healthy volunteer patients were also enrolled and represented the control group (group III). Results. We enrolled 307 patients (107 in group I and 200 in group II) with arterial aneurysm: 49 popliteal, 31 common femoral, 2 superficial femoral, 29 common iliac artery, 3 common carotid, and 193 abdominal aorta. Finally, 11 healthy volunteer patients (9 males and 2 females; age range, 40–70 years; median 56) were enrolled in group III. Enzyme-linked immunosorbent assay and Western blot analysis revealed greater levels of immunoreactive MMP-9 and NGAL in all patients with ruptured aneurysms, both central and peripheral aneurysms, and in the aneurismal vessels. Conclusion. These results provide potentially important insights to the understanding of the natural history of arterial aneurysms. MMPs and NGAL play a role in development of arterial aneurysms and may represent molecular markers for the prevention of aneurysmal rupture

Resection of carotid body tumors reduces arterial blood pressure. An understimated neuroendocrine syndrome

ntroduction: Carotid Body Tumors (CBTs) are Paragangliomas (PGLs) located in the head and neck region which usually do not cause overt neuroendocrine symptoms and hypertension. Matrix Metal- loproteinases (MMPs) have shown a strong correlation between CBTs and their clinical behavior. Aim of this study is to analyze the relationship between changes in arterial blood pressure and metal- loproteinases levels after surgical resection of CBTs. Methods: We performed a multicenter clinical study on 17 patients with benign and malignant CBTs (5 males; 12 females). Tumors were completely resected and biopsies, obtained at the time of surgery, were lysed for Western blot analysis to determine MMPs levels in tissues. An enzyme-linked immune sorbent assay (ELISA) kit was used to determine the concentration of MMPs in plasma fluid. Blood pressure values were measured at admission and at 10 days after surgery. Results: At the time of the admission, blood pressure values were higher in patients with CBTs respect to control patients; moreover in patients with malignant CBTs blood pressure values were higher (P < 0.01) respect to patients with benign CBTs. 10 days after the surgery, we documented a significant decrease (P < 0.01) in blood pressure values and in MMPs levels in all patients with CBTs. Conclusion: These results suggest that, despite the CTBs are considered non-functional tumors, an “underestimated” neuroendocrine activity on arterial blood pressure may be detecte

Effects of a new nutraceutical substance on clinical and molecular parameters in patients with chronic venous ulceration.

Pathophysiological events involved in the onset of chronic venous ulceration (CVU) are inflammation, activation of polymorphonucleates (PMNs) and secretion of proteases such as matrix metalloproteinases (MMPs), which degrade extracellular matrix (ECM) that is a support for vascular and tissutal wall. MMPs, neutrophil gelatinase-associated lipocalin (NGAL) and inflammatory cytokines are overexpressed in CVUs and they could play a central role in pathophysiological mechanisms of skin lesion and delayed wound healing. Bioflavonoids, such as diosmin and other compounds, appear to have several provessel function activities including anti-inflammatory, antioxidant and phlebotonic effects and are widely used in the treatment of chronic venous disease (CVD)-related problems. In this article, we evaluated the effects of Axaven®, a new nutraceutical on both clinical and molecular parameters in patients with CVUs. During the study period, 83 patients with CVUs of both sexes were enrolled and divided into two groups: group A (treated group): 25 females and 19 males (median age is 67⋅7 years) received standard treatment (compression therapy and surgical correction of superficial venous incompetence) + Axaven® once a day for 8 months as adjunctive treatment. Group B (control group): 24 females and 15 males (median age is 65⋅2 years) were treated only with basic treatment according to their clinical conditions. In our study, the administration of Axaven® in patients with CVUs was able to decrease inflammatory cytokines, MMPs and NGAL, inducing an improvement of both symptoms with an increase of the speed of wound healing