Treatment of type B aortic dissection: endoluminal repair or conventional medical therapy?

OBJECTIVE: To evaluate the mid-term results of endovascular stent-grafting for type B aortic dissection, in comparison with those of standard medical therapy in uncomplicated cases. METHODS: Between January 1999 and 2004, among 56 patients (mean age 59.5+/-11.5 years) with type B aortic dissection, hypotensive medical therapy was the only treatment in 28 uncomplicated cases, (group A), while stent-graft implantation was performed in 28 patients with uncontrolled hypertension, persistent pain or evidence of dissection progression or complication (group B). In 14 cases (50%) the procedure was performed in an acute setting. Stent-grafting procedures were monitored with intraoperative trans-esophageal echocardiography and cine-angiography. CT scan and trans-esophageal echocardiography were performed before hospital discharge, at 6 and 12 months and then yearly. RESULTS: Follow-up (range 1-61 months, average 18.1+/-16.9 months) was 100% complete. In-hospital mortality was 10.7% (three patients, all belonging to Group B; P=0.24). No spinal cord injuries were observed. Early endoleak occurred in one patient (3.5%). Mid-term mortality was lower in Group B, although the difference was not significant (10.7 versus 14.3% in Group A, P=0.71). Follow-up CT scans evidenced complete thrombosis of the false lumen in 75% cases in Group B, 10.7% in Group A (P=0.0001), and an aneurismal dilatation of the descending aorta in 3.5% cases in Group B, 28.5% in Group A (P=0.02). CONCLUSIONS: Although with still considerable early mortality, endovascular stent-graft implantation is an effective option for the treatment of complicated type B aortic dissection. Endovascular treatment achieved a better mid-term fate of the descending thoracic aorta than medical therapy alone, even in patients with worse preoperative conditions.     

Effects of atorvastatin on arterial endothelial function in coronary bypass surgery

Objective: Endothelial dysfunction represents a critical early component of organ injury following cardiopulmonary bypass. Recent studies demonstrate that the treatment with atorvastatin is associated with a significant improvement of endothelial function independently of its efficacy on cholesterol levels. Therefore, we investigated the effects of preoperative atorvastatin treatment on endothelium function after coronary surgery. Methods: Forty patients undergoing coronary surgery were randomized to treatment with atorvastatin (20 mg/die; N = 20) or placebo (N = 20) 3 weeks before surgery. Twenty normal patients served as control group. The flow-mediated dilations (FMD) of the brachial artery after both reactive hyperemia (endothelium dependent) and nitroglycerin administration (endothelium independent) were evaluated at baseline, at 48 h, and 5 days postoperatively. Results: At baseline, the endothelium-dependent FMD was significantly attenuated in coronary versus normal patients (normal 10.3 ± 1.8% vs coronary 4.1 ± 1.6%, p < 0.01). At 48 h postoperatively all patients exhibited a reduced FMD compared with baseline values: the endothelium-dependent dilatation showed a drop of 60.1 + 15% in the patients of the placebo group compared with 45.8 + 16.6% (p < 0.05) those in the atorvastatin group. At the univariate analysis, no significant correlation was found between serum levels of either total cholesterol or HDL cholesterol and FMD. The nitroglycerin-induced dilation was not significantly influenced by extracorporeal circulation as well as by atorvastatin treatment. Conclusions: The endothelial dysfunction following cardiopulmonary bypass is improved by the treatment with atorvastatin, by a mechanism unrelated to the drug efficacy of controlling serum cholesterol levels.     

Multidimensional analysis of the symptoms of chronic bronchitis and emphysema

Subjective symptoms and experiences were explored within a group of 146 severe, chronic bronchitis and emphysema patients. Eighty-nine symptoms and experiences, derived from initial interviews with 29 patients, were rated according to the frequency of occurrence during breathing difficulties. Key cluster analyses were used to derive a Bronchitis-Emphysema Symptom Checklist (BESC) measuring 11 symptom categories: Helplessness-Hopelessness, Decathexis, Fatigue, Poor Memory, Peripheral-Sensory Complaints, Dyspnea, Congestion, Sleep Difficulties, Irritability, Anxiety, and Alienation. The BESC symptom categories are highly reliable and the relationships among categories are stable across two subgroups of patients. The BESC provides one way to describe how patients cope with and experience chronic bronchitis and emphysema.     

Induction of immune tolerance in patients with hemophilia A and inhibitors treated with porcine VIIIC by home therapy

Home therapy with porcine factor VIIIC was safe and effective when administered to five hemophilic patients over periods of 8 1/2, 6, 4, 3 1/2, and 2 years. No significant transfusion reactions occurred. Before treatment with porcine factor VIIIC, all five had high-level, high- responding anti-human VIIIC inhibitors initially lacking anti-porcine factor VIIIC activity. Although specific anti-porcine VIIIC inhibitors arose in all patients, these were generally transient, and only one patient became refractory to treatment. We believe that porcine factor VIIIC is the treatment of choice in patients whose inhibitors do not cross-react. All five patients lost their original anti-human VIIIC inhibitors after starting treatment with porcine VIIIC, permitting the reintroduction of human VIIIC in three of them. There has been no recurrence of anti-human VIIIC inhibitor activity during 2 to 3 years of regular treatment with human VIIIC in these patients. This suggests that tolerance to human VIIIC has arisen as a result of treatment with porcine VIIIC. Porcine VIIIC may have a role in the desensitization of some factor VIIIC inhibitor patients.     

Contrast-enhanced gray-scale harmonic ultrasound in the efficacy assessment of ablation treatments for hepatocellular carcinoma.

BACKGROUND: The aim of this study was to compare contrast-enhanced gray-scale harmonic ultrasound with multiphasic spiral computed tomography in the assessment of treatment efficacy of non-surgically treated HCC. METHODS: We studied 56 HCCs treated by percutaneous ethanol injection (31 cases), radiofrequency ablation (three cases), trans-arterial chemoembolization (12 cases), and combined treatment (10 cases). The efficacy of therapies was blindly assessed by multiphasic computed tomography and gray-scale harmonic ultrasound with a second-generation contrast agent (sulfur hexafluoride). RESULTS: On computed tomography 30 tumors (53.6%) showed complete necrosis, while 26 lesions (45.4%) were still viable. On contrast-enhanced ultrasound examination 33/56 nodules (58.9%) had no contrast enhancement in the arterial phase, while 23/56 lesions (41.1%) were still vascularized. All the nodules assessed as completely necrotic on computed tomography did not show arterial enhancement on contrast-enhanced ultrasound and diagnostic agreement was found in 53/56 cases (94.6%) (P<0.001). Contrast-enhanced ultrasound demonstrated relative sensitivity and specificity of 87.0% and 98.4%. CONCLUSIONS: Contrast-enhanced harmonic ultrasound is promising in the efficacy evaluation of ablation treatments for HCC. Nodules vascularized in the arterial phase on contrast harmonic ultrasound should be considered still viable and addressed to additional treatment without further evaluation.     

Locus assignment of two alpha-globin structural mutants from the Caribbean basin: alpha Fort de France (alpha 45 Arg) and alpha Spanish Town (alpha 27 Val)

Two alpha-globin structural mutants were mapped to their encoding loci by in vitro translation of hybrid-selected alpha 1- and alpha 2-globin mRNA. The more highly expressed mutant, alpha Spanish Town (alpha 27Val), is encoded at the alpha 2 locus and the less expressed mutant, alpha Fort de France (alpha 45Arg), is encoded at the alpha 1 locus. These results further define the distribution of alpha-globin structural mutations within the alpha-globin gene cluster and substantiate the dominant role of the alpha 2-globin locus in alpha- globin expression.     

Simvastatin attenuates the endothelial pro-thrombotic shift in saphenous vein grafts induced by Advanced glycation endproducts

Background

Advanced glycation endproducts (AGEs) and its receptors (RAGEs) are heterogeneous signaling proteins associated to diabetes and responsible of endothelial alterations leading to atherosclerosis progression and graft failure. The aim of this study was to investigate the role of statin in reducing AGEs related endothelial damage.

Methods

Endothelial cell(EC) obtained from leftovers of saphenous vein grafts of non-diabetic patients were incubated with AGEs (2 and 20 μM) and subsequently treated with Simvastatin. Neutrophils (PNM) adherence, ROS production and RAGE and peroxisome proliferator-activated receptors-gamma (PPAR-γ) expression were analyzed. As clinical validation of the in vitro findings, ECs of diabetic patients in optimized glycaemic control administered with a 3 weeks Simvastatin regimen were similarly processed.

Results

Simvastatin blunted the rise in PMN adhesion and ROS generation following stimulation of saphenous vein EC culture with AGEs in vitro. This effect was time dependent and was associated to an increase in PPAR-γ induction paralleled by a decrease in RAGEs expression. Parallely, data from diabetic patients administered with Simvastatin showed a similar significant reduction in PNM adhesion and ROS generation. Simvastatin treatment significantly decreased RAGEs expression in ECs from diabetic patients and determined a slight increase in PPAR-γ expression but the latter failed to reach statistical significance. Interference in the function of these two crucial pathways might be at the root of the statin antinflammatory and antithrombotic effect in the context of AGEs-associated damage.

Conclusions

Despite the recently raised warning on the use of statins in the diabetic population, this study elucidates their cornerstone position in endothelial homeostasis of saphenous grafts in patients with controlled diabetes.