Predictive factors of stroke in patients undergoing coronary bypass grafting: statins are protective.

BACKGROUND: Despite major improvement in surgical techniques and intensive care management, stroke remains one of the most devastating complications of coronary artery bypass grafting (CABG). We aimed to determine factors predicting the occurrence of stroke during CABG. A special interest was focused on preoperative therapies. METHODS: We prospectively enrolled 810 consecutive candidates for CABG alone in a specific database, including all pre- and perioperative data (history, clinical, therapeutic, cardiac catheterization, surgical and intensive care data). Univariate tests and then multiple logistic regression analysis were used to determine independent predictive factors. RESULTS: During the first postoperative month, stroke occurred in 11 cases and transient ischemic attack (TIA) in 4 additive cases (cumulative rate: 1.85%). After the multivariate analysis, the following factors remained significant (p<0.05) in the predictive model, with corresponding odds ratios between brackets: redo cardiac surgery (7.45), unstable cardiac status (4.74), past history of cerebrovascular disease (4.14), past history of peripheral arterial disease (3.55), whereas the presence of preoperative statins was protective (0.24, 95% IC: 0.07-0.78). The addition of perioperative data (aortic calcification, postoperative arrhythmia, on/off-pump surgery) did not change the final predictive model. CONCLUSION: To our knowledge, this is the first real-world observational report highlighting the interest of statins for the prevention of stroke in the very special situation of CABG. Even though according to randomized trials coronary patients have a benefit from these drugs, a special level of interest should be directed towards those presenting the above-mentioned risk factors.     

Surgical management of bile duct injuries following laparoscopic cholecystectomy: analysis and follow-up of 28 cases

BACKGROUND: Biliary tract lesions pose a dreaded complication of laparoscopic cholecystectomy. In a retrospective study we analyzed the clinical presentation, diagnostic and therapeutic management and outcome of 28 patients presenting with iatrogenic bile duct injuries. PATIENTS AND METHODS: Between 1994 and 2001 we treated 28 patients with bile duct lesions following laparoscopic cholecystectomy at our center. Operation notes and charts of all patients were reviewed systematically. A follow-up examination of each patient was performed after a median of 12 months (range 1-90). RESULTS: Twenty-two patients presented with major circumferential bile duct defect lesions. Less severe injuries (n=6) were two minor bile leaks, one bile duct stricture and three tangential lesions. Twenty-six patients were referred to our institution within 16 days (range 0-226 days). Six patients were treated by nonsurgical procedures: endoscopic stenting in four and percutaneous intervention in two. In one of the remaining patients a cystic duct leak was closed via laparotomy, and in 21 a hepaticojejunostomy was performed. Reconstruction of a hepaticojenunostomy was performed in two of these patients. Patients were dismissed from the hospital after a median of 13 days (range 4-156). Four patients presenting with generalized biliary peritonitis required prolonged intensive care. One or more episodes of cholangitis were seen in five patients during follow-up examinations. CONCLUSIONS: Major iatrogenic bile duct injuries are associated with high morbidity and prolonged hospitalization. Interdisciplinary cooperation and early referral to an experienced center is crucial in the management of patients suffering from this affliction. Cholangitis is a marked problem in the follow-up.     

EFNS Guidelines on diagnosis and treatment of brain metastases: report of an EFNS Task Force

The objectives have been to establish evidence-based guidelines and identify controversies regarding the management of patients with brain metastases. The collection of scientific data was obtained by consulting the Cochrane Library, bibliographic databases, overview papers and previous guidelines from scientific societies and organizations. A tissue diagnosis is necessary when the primary tumor is unknown or the aspect on computed tomography/magnetic resonance imaging is atypical. Dexamethasone is the corticosteroid of choice for cerebral edema. Anticonvulsants should not be prescribed prophylactically. Surgery should be considered in patients with up to three brain metastases, being effective in prolonging survival when the systemic disease is absent/controlled and the performance status is high. Stereotactic radiosurgery should be considered in patients with metastases of 3–3.5 cm of maximum diameter. Whole-brain radiotherapy (WBRT) after surgery or radiosurgery is debated: in case of absent/controlled systemic cancer and Karnofsky Performance score of 70 or more, one can either withhold initial WBRT or deliver early WBRT with conventional fractionation to avoid late neurotoxicity. WBRT alone is the treatment of choice for patients with single or multiple brain metastases not amenable to surgery or radiosurgery. Chemotherapy may be the initial treatment for patients with brain metastases from chemosensitive tumors.     

Deregulation of cell proliferation by polycyclic aromatic hydrocarbons in human breast carcinoma MCF-7 cells reflects both genotoxic and nongenotoxic events.

Polycyclic aromatic hydrocarbons (PAHs), such as benzo[a]pyrene (BaP), are carcinogens suggested to be involved in development of human cancer. Several recent studies have reported that PAHs can activate estrogen receptors (ER), either directly or indirectly by producing estrogenic metabolites. We hypothesized that the activation of ER by PAHs or their metabolites could induce cell proliferation in estrogen-sensitive cells. In the present study, we found that two PAHs, benz[a]anthracene (BaA) and BaP, can stimulate proliferation of human breast carcinoma MCF-7 cells at concentrations 100 nM and higher. This effect was ER-dependent, because it was blocked by the pure antiestrogen ICI 182,780. Although both PAHs partially inhibited S-phase entry and DNA synthesis induced by 17beta-estradiol, they stimulated S-phase entry when applied to MCF-7 cells synchronized by serum deprivation. This was in contrast with model antiestrogenic aryl hydrocarbon receptor ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin, which fully suppressed S-phase entry. BaP, which is a strong mutagen, was found to induce p53 tumor suppressor expression, a partial S-phase arrest and at higher concentrations also cell death. Pifithrin-alpha, a synthetic inhibitor of p53 activity, abolished both S-phase arrest and apoptosis induced by genotoxic PAHs, and it potentiated the proliferative effect of BaP. Thus, both genotoxic and nongenotoxic events seem to interact in the effects of BaP on cell proliferation. Taken together, our data indicate that both BaA and BaP can stimulate cell proliferation through activation of ER. The proliferative effects of these carcinogenic compounds might contribute to tumor promotion in estrogen-sensitive tissues.     

Carotid intima-media thickness as predictor of secondary events after coronary angioplasty.

AIM: Subjects with symptomatic or asymptomatic peripheral arterial or cerebro-vascular disease have an increased risk of death or cardiovascular event. The aim of this study was to determine whether intima-media thickening of the common carotid artery and/or a low ankle brachial index (ABI) are related with an increased risk of cardio-vascular event after percutaneous coronary angioplasty (PTCA). METHODS: One hundred and thirteen consecutive, patients (88 males, 25 females, mean age: 62 years) undergoing PTCA were included. Intima media thickness (IMT) of the common carotid artery and ABI were measured within the 2 days following the PTCA. Subjects were followed up for 10.2 +/- 4 months. The end-point was a composite criterion associating death, non fatal acute myocardial infarction, recurrence or worsening of angina pectoris, hospitalisation for heart failure, new positive exercise stress testing. RESULTS: In the follow-up study a common carotid IMT >0.7 mm was a predictor of event (p=0.03) in the univariate analysis. The other risk factors were unstable angina (p=0.001) and PTCA on the left descending coronary artery (p<0.05). We did not find any relation between the end-point and ABI or presence of atheroma on the common femoral artery. In the logistic regression analysis unstable angina was associated with a 3.14 fold increased risk (IC 95%: 1.51-6.4, p=0.002), subjects without HMG-CoA inhibitors drugs at the inclusion had also an increased risk of 2.5 (IC 95%:1.09-5.75, p=0.02). CONCLUSION: This study suggest that CCA-IMT is associated with an increased risk of cardiac events after PTCA. The measurement of subclinical disease could be useful for identifying high-risk patients.     

Neuroimmune interactions in the airways: Implications for asthma, allergy, and other inflammatory airway diseases

Recent evidence suggests that several bioactive polypeptides, among them substance P, neurokinin A, and calcitonin gene-related peptide, are contained in tracheobronchial C-fibers. These peptides can be released from the lung by irritant chemicals or local inflammatory mediators like histamine or bradykinin. Substance P mimicks the increase in vascular permeability caused by vagal nerve stimulation and neurokinin A mimicks noncholinergic bronchoconstriction by vagal nerve stimulation. Calcitonin gene-related peptide displays vasodilator activity. Experiments carried out with sensitized guinea pigs showed a contribution of tracheobronchial C-fibers to the anaphylactic response. Additionally, capsaicin, which in high concentration selectively blocks sensory C-fibers, was found to be effective in treatment of hyperreactive rhinopathy (vasomotor rhinitis). It is concluded that peptide mediators released from tracheobronchial C-fibers may contribute to the pathophysiology of various allergic or inflammatory airway diseases.     

Kidney transplantation in patients with Wilms' tumor.

We report our experience of renal transplantation in three patients treated for Wilms' tumor (with lung metastasis in two of them), and review 26 previously reported cases in order to define the current indications of transplantation in this setting. Our patients, aged 5-12 years, were transplanted 13-95 months after completion of Wilms' tumor treatment. All three are alive and tumor-free, two with a functioning graft 20 and 97 months after transplantation. Two findings emerge from the review of the literature. First, posttransplant mortality is influenced by the delay between completion of tumor treatment and transplantation. Mortality reaches 79% when that delay is less than one year but falls to 27% when that delay exceeds one year. Second, the prognostic value of pretransplant metastasis depends on its location. All four patients with pretransplant abdominal metastasis died with active metastatic disease. By contrast, of three patients treated before transplantation for metastasis confined to the lung, two are alive and tumor free. We conclude that renal transplantation should be offered to patients successfully treated for Wilms' tumor for at least one year, even if the disease has been complicated by pulmonary metastasis. Several long-term survivors attest that the disease can be cured even under maintenance immunosuppression.