SPAG5 promotes proliferation and suppresses apoptosis in bladder urothelial carcinoma by upregulating Wnt3 via activating the AKT/mTOR pathway and predicts poorer survival.

Sperm-associated antigen 5 (SPAG5) is involved in various biological processes. However, the roles of SPAG5 in bladder urothelial carcinoma (BUC) are unknown. This study showed that upregulation of SPAG5 was detected frequently in primary BUC tissues, and was associated with significantly worse survival among the 112 patients that underwent radical cystectomy (RC). Up and downregulating the expression of SPAG5 enhanced or inhibited, respectively, the proliferation of BUC cells in vitro and in vivo, and suppressed or enhanced, respectively, apoptosis in vitro and in vivo. Moreover, SPAG5 increased the resistance of BUC cells to chemotherapy-induced apoptosis. Mechanistic investigations showed that SPAG5 promotes proliferation and suppresses apoptosis in BUC at least partially via upregulating Wnt3 through activating the AKT/mTOR signaling pathway. The importance of the SPAG5/AKT-mTOR/Wnt3 axis identified in BUC cell models was confirmed via immunohistochemical analysis of a cohort of human BUC specimens that underwent RC. Collectively, our data suggested that in patients with BUC who underwent RC, high SPAG5 expression is associated with poor survival. In addition, targeting SPAG5 might represent a novel therapeutic strategy to improve the survival of patients with BUC.

Comparison of pharmacodynamic effects of ticagrelor vs prasugrel in type 2 diabetes mellitus patients with coronary heart disease.

WHAT IS KNOWN AND OBJECTIVE: Patients with type 2 diabetes mellitus (T2DM) are at higher risk of thrombotic complications. Studies have indicated that patients with T2DM have impaired clopidogrel-induced antiplatelet effect. Ticagrelor and prasugrel are two latest generation P2Y12 inhibitors with advantageous platelet inhibitory profiles. However, the pharmacodynamic differences between the two drugs in patients with T2DM remain poorly explored. METHODS: This study, involving 140 patients with T2DM following percutaneous coronary intervention (PCI), evaluated the efficacy of aspirin upon concomitant use of prasugrel (10 mg/d) or ticagrelor (90 mg/d). Platelet reactivity was assessed by value of ADP-induced light transmittance aggregometry (LTA) and vasodilator-stimulated phosphoprotein phosphorylation-platelet reactivity index (VASP-PRI) at baseline, 7 and 30 days after randomized P2Y12 inhibitor treatment. RESULTS: The study showed a decreased platelet reactivity after use of P2Y12 inhibitors (both P < .001). On the basis of comparison between regimens, apart from the prasugrel group having a significantly higher LTA value at the 30-day time point (P = .043), there existed no significant differences in platelet reactivity at separate time points (all P > .05). As for intragroup measurements, when compared with 7-day and 30-day time points, similar platelet reactivity was documented in the ticagrelor group (both P > .05), but LTA tests showed a significant increase with time (days 7-30) in the prasugrel group (P = .050). WHAT IS NEW AND CONCLUSION: Although ticagrelor and prasugrel have similar platelet inhibitory effects in patients with T2DM, if a P2Y12 inhibitor is necessitated in patients with T2DM, ticagrelor might exert a more stable antiplatelet effect with 30-day short-term treatment.

SPREAD Italian Guidelines for stroke. Indications for carotid endarterectomy and stenting.

This multidisciplinary guideline provides an overview of the current evidence on the benefits obtained by endoarterectomy and stenting for the surgical treatment of patients with symptomatic and asymptomatic carotid stenosis. A hundred forty-six authors, 37 Italian scientific societies and two Italian patients' associations participated in drafting the Stroke Prevention and Educational Awareness Diffusion (SPREAD) document, which has become the national guideline for the prevention and treatment of stroke in Italy. For the surgical therapy section of this document, the main trials on carotid endoarterectomy and stenting were critically reviewed following The Scottish Intercollegiate Guideline Network Oxford Centre for Evidence-Based Medicine methodology in order to formulate recommendations and syntheses for these procedures. The final document was peer reviewed and approved by all the participants. Recommendations and syntheses are presented for the referral of patients to either carotid endoarterectomy or stenting on the basis of whether carotid stenosis is symptomatic or asymptomatic, on the presence of various risk factors such as degree of arterial narrowing, and on concomitant pathology (cardiopathy and acute stroke).

Eversion versus conventional carotid endarterectomy for preventing stroke.

BACKGROUND: Carotid endarterectomy is conventionally undertaken by a longitudinal arteriotomy. Eversion carotid endarterectomy (CEA), which employs a transverse arteriotomy and reimplantation of the carotid artery, is reported to be associated with low perioperative stroke and restenosis rates but an increased risk of complications associated with a distal intimal flap. OBJECTIVES: The objective of this review was to determine whether eversion CEA was safe and more effective than conventional CEA. The null-hypothesis was that there was no difference between the eversion and the conventional CEA techniques (performed either with primary closure or patch angioplasty). SEARCH STRATEGY: The reviewers searched MEDLINE and the Cochrane Stroke Group Trials Register (last searched: December 1999), and hand searched eight surgical journals and conference proceedings. Researchers were contacted to identify additional published and unpublished studies. SELECTION CRITERIA: All randomised trials comparing eversion to conventional techniques in patients undergoing carotid endarterectomy were examined in this review. Outcomes were stroke and death, carotid restenosis/occlusion and local complications. DATA COLLECTION AND ANALYSIS: Data were extracted independently by two reviewers to assess eligibility and describe trial characteristics, and by one reviewer for the meta-analyses. Discrepancies were resolved by discussion. When possible, unpublished data were obtained from investigators. MAIN RESULTS: Five trials were included for a total of 2465 patients and 2590 arteries. Three trials included bilateral carotid endarterectomies. In one trial, arteries rather than patients were randomised so that it was not clear how many patients had been randomised in each group, therefore, information on the risk of stroke and death from this study were considered in a separate analysis. There were no significant differences in the rate of perioperative stroke and/or death (1.7% vs 2.6%, odds ratio [OR] 0.44, 95% confidence interval [CI] 0.10-1.82) and stroke during follow-up (1.4% vs 1.7%, OR: 0.84, 95% CI: 0.43-1.64) between eversion and conventional CEA techniques. Eversion CEA was associated with a significantly lower rate of restenosis >50% during follow-up (2.5% vs 5.2%, OR: 0.48, 95% CI: 0.32 -0.72). However, there was no evidence that the eversion technique for CEA was associated with a lower rate of neurological events when compared to conventional CEA. There were no statistically significant differences in local complications between the eversion and conventional group. No data were available to define the cost-benefit of eversion CEA technique. REVIEWER'S CONCLUSIONS: Eversion CEA may be associated with low risk of arterial occlusion and restenosis. However, numbers are too small to definitively assess benefits or harms. Reduced restenosis rates did not appear to be associated with clinical benefit in terms of reduced stroke risk, either perioperatively or later. Until further evidence is available, the choice of the CEA technique should depend on the experience and familiarity of the individual surgeon.

Angiotensin-converting enzyme gene I/D polymorphism and carotid artery disease in renovascular hypertension.

There is evidence linking the activation of the renin-angiotensin system (RAS) with target organ damage in renovascular hypertension (RVH). A genetic association of the DD genotype of the angiotensin-converting enzyme (ACE) gene with cardiovascular complications has been found in various clinical conditions. The aim of our study was to determine whether the insertion/deletion (I/D) polymorphism of the ACE gene is associated with the high prevalence of target organ damage reported in RVH. A total of 65 atherosclerotic patients (age 68.2 +/- 5.2 years) with RVH and 49 atherosclerotic patients (age 68.0 +/- 6.3 years) with essential hypertension (EH) were sequentially enrolled when attending the outpatient clinic for specialist assessment of their vascular disorder. Cardiac, renal, and vascular involvement were assessed in both groups and blood was taken for genetic analysis. Patients with RVH had a higher prevalence of left ventricular hypertrophy (LVH), carotid artery disease, and albuminuria than those with EH. In RVH, but not in EH, the DD genotype was significantly associated with severe arterial disease. In RVH, carotid disease (lumen narrowing >60%) was present in 62% of DD patients versus 25% of the other genotypes (OR = 4.90, 95% CI: 1.70-14.13). Such an association was also present in peripheral vascular disease: 72.4% in DD patients versus 41.6% in the other genotypes (OR = 3.67, 95% CI = 1.29-10.36). Logistic regression analysis showed that the DD genotype was the strongest predictor of risk of severe carotid disease. We conclude that, in atherosclerotic RVH, there is an association of the severity of vascular disease with the DD genotype of the ACE gene.

ACE gene polymorphism and survival in atherosclerotic renovascular disease.

Renovascular disease (RVD) is an important cause of end-stage renal disease and is associated with a high mortality rate, mostly because of coexisting cardiovascular and cerebrovascular disease. The deletion (DD) polymorphism of the angiotensin-converting enzyme (ACE) gene has been described in association with severe vascular disease affecting major organs. To investigate whether DD genotype is a risk factor for mortality in RVD, we performed a follow-up study of 61 patients with this disease. Patients (age, 68.0 +/- 6.5 years) affected by atherosclerotic vascular disease were enrolled after angiographic demonstration of a renal artery stenosis. The average follow-up was 48.1 +/- 14.9 months. Genotype was insertion/deletion (I/D) in 30 patients, DD in 27 patients, and II in 4 patients. At enrollment, a complete assessment of heart, blood vessels, and renal function was performed. During the follow-up period, 13 patients died (9 DD, 4 ID) and 7 patients evolved into end-stage renal failure. The cumulative survival rate at 5 years was 45.4% +/- 13.4%. Factors associated with mortality were analyzed with Cox proportional hazard regression. The multivariate analysis showed that DD genotype, severe carotid disease, and smoking were independent predictors of mortality. The multivariate analysis of predictors of renal failure showed that the only significant association was found with baseline serum creatinine level of 265 micromol/L or greater. We conclude that the DD genotype of the ACE gene is a marker for mortality in RVD.

Survival of patients with renovascular disease and ACE inhibition.

AIM: Renovascular hypertension (RVH) is associated with a high prevalence of target organ damage and a high mortality. We have undertaken this follow-up study to assess the role played by comorbid conditions, and pharmacological treatment on survival, and on renal function in 64 patients with diffuse atherosclerotic vascular and renovascular disease (RVD). PATIENTS AND METHODS: The patients were followed for an average period of 37.3+/-20.4 months. RESULTS: At the end of the follow-up we found a cumulative survival at 5 years of 60%+/-10. Cerebrovascular and cardiovascular disease were responsible for 92% of deaths. A decrease in creatinine clearance >10 ml/min at 5 years was found in 65% of patients, 3 of whom ended in dialysis. Multivariate analysis of predictors of survival showed that treatment with angiotensin converting enzyme inhibitors (ACEi) was significantly associated with a favourable outcome (p = 0.019). Conversely, proteinuria had a negative effect. Renal survival was best predicted by the level of renal function at entry (p = 0.02), and was not influenced by pharmacological treatment. CONCLUSION: We conclude that ACEi exerts a beneficial effect on survival without affecting renal function in patients with RVD due to unilateral renal stenosis.

European multicentre experience with modular device (Medtronic Aneurx) for the endoluminal repair of infrarenal abdominal aortic aneurysms.

OBJECTIVE: Transfemoral endoluminal repair of AAA, introduced for the first time in the early 90's, has become a very promising alternative to conventional open repair and more and more centers are reporting satisfactory postoperative results in a high percentage of cases. Straight and bifurcated grafts represent the devices available on the market at present and aortic, as well as iliac aneurysmal lesions can be safely treated through a transfemoral approach. The possibility to indicate an endovascular AAA repair is related to the configuration (length and size) of the proximal and distal necks, tortuosity and calcification of the access arteries and to vascular and non-vascular comorbidities, which afflict the patients. The objective of our study was to evaluate the early and late postoperative results in a series of patients affected by infrarenal AAA, who underwent endoluminal repair. MATERIALS AND METHODS: From December 1996 to 31 October 1997 in 5 different European Centers, 100 Medtronic AneuRx bifurcated stent grafts were implanted for infrarenal abdominal aortic aneurysms. The diameter of the AAA varied from 33 to 77 mm (average 64 mm) and the mean age of the patients was 70.8 years (51-87 years). In one patient with a 33 mm diameter of the aneurysm, the surgical procedure was indicated because the size of the aneurysm had increased by 5 mm, compared to the previous control made 2 months before. In addition the aneurysm became symptomatic. There were 92 male and 8 female patients. The average time of the surgical procedure was 150 minutes (75-480 minutes) with an average blood loss of 570 ml (100-2,600 ml).

[The magnetic resonance imaging of abdominal aortic aneurysms]. / L'imaging con Risonanza Magnetica degli aneurismi dell'aorta addominale.

The diagnostic role of Magnetic Resonance Imaging (MRI) was investigated in the study of abdominal aortic aneurysms and compared with that of Computed Tomography (CT) and digital subtraction angiography (DSA). Magnetic Resonance angiography (MRA) was performed on 21 patients with radiologically proved abdominal aortic aneurysms, using a superconductive 1.5 T magnet (GE, Signa Advantage); the 2D TOF technique with gradient-echo sequences was used (SPGR: FA 45-60 degrees, TR/TE 33/7, ST 2 mm, 1 nex, 256 x 128 matrix, inferior presaturation and flow compensation). The images acquired on the axial plane were reconstructed according to MIP and rotated on the z-axis from +90 degrees to -90 degrees. In all cases SE 2D T1- and T2-weighted sequences were acquired on the axial plane. Twelve patients were examined with MRI, CT and DSA; 3 with MRI and CT; 2 with MRI and DSA and finally 4 with MRI only. The radiologic studies were then reviewed blind and the results of the different methods compared. In all cases MRI yielded similar information to CT and DSA as to aneurysm extent and size, vessel involvement, status of visceral, iliac and common femoral arteries and finally the conditions of perianeurysmatic tissues. The authors conclude that MRI is a useful and accurate technique for the preoperative examination of abdominal aortic aneurysm patients.

[Loco-regional fibrinolysis in peripheral arterial bypasses. Our experience]. / La fibrinolisi loco-regionale nei bypass arteriosi periferici. Nostra esperienza.

Thirty-one patients (29 males and 2 females) with 34 thrombosed grafts were treated by direct intra-arterial infusion of urokinase; the lesions were acute in 27 cases and chronic (2-4 months) in 4. Urokinase was infused in doses of 50,000 UI/h. Angiographic follow-up exams were performed every 12 hours. The infusion was stopped when lumen patency was re-established and there was no significant mural thrombus or peripheral embolus. Treatment usually lasted 4-72 hours (average: 18 hours). The hematological status was controlled by measuring plasma fibrinogen, coagulation time, partial thromboplastin time, prothrombin and antiplasmin time. Initial success rate was 76% (23 patients). Overall 1-year patency was 56% in 23 cases: 85% in the patients with correctable lesions by means of surgery or PTA, and 46% in the patients with non-correctable lesions. After the first period, patency remained high in the patients followed up to 5 years. Our experience confirms that lysis of a thrombosed graft is possible by the local infusion of a low-dose fibrinolytic agent and exhibits high success rate and low complication rate in acute and chronic obstructions.

[Gardner's syndrome and mediastinal sarcoma. Description of a clinical case and review of the literature]. / Sindrome di Gardner e sarcoma mediastinico. Descrizione di un caso clinico ed esame della letteratura.

The incidence of the colonic and rectal polyps cancerisation in patients with Gardner's syndrome is very high. In these patients, on the other hand, the extraintestinal tumours very rarely degenerative in cancer. A case of mediastinal sarcoma in a patient with Gardner's syndrome is reported.