PURPOSE: The purpose of the trial was to quantify and compare the efficacy of two different sequences of burst anti-tachycardia pacing (ATP) strategies for the termination of fast ventricular tachycardia. METHODS: The trial was prospective, multicenter, parallel and randomized, enrolling patients with an indication for implantable cardioverter-defibrillator implantation. RESULTS: From February 2004, 925 patients were randomized and followed-up for 12 months. Eight pulses ATP terminated 64% of episodes vs. 70% in the 15-pulse group (p = 0.504). Fifteen pulses proved significantly better in patients without a previous history of heart failure (p = 0.014) and in patients with LVEF >/= 40%(p = 0.016). No significant differences between groups were observed with regard to syncope/near-syncope occurrence. CONCLUSION: In the general population, 15-pulse ATP is as effective and safe as eight-pulse ATP. The efficacy of ATP on fast ventricular arrhythmias confirmed once more the striking importance of careful device programming in order to reduce painful shocks.

A specific neuronal vulnerability to amyloid protein toxicity may account for brain susceptibility to protein misfolding diseases. To investigate this issue, we compared the effects induced by oligomers from salmon calcitonin (sCTOs), a neurotoxic amyloid protein, on cells of different histogenesis: mature and immature primary hippocampal neurons, primary astrocytes, MG63 osteoblasts and NIH-3T3 fibroblasts. In mature neurons, sCTOs increased apoptosis and induced neuritic and synaptic damages similar to those caused by amyloid beta oligomers. Immature neurons and the other cell types showed no cytotoxicity. CTOs caused cytosolic Ca(2+) rise in mature, but not in immature neurons and the other cell types. Comparison of plasma membrane lipid composition showed that mature neurons had the highest content in lipid rafts, suggesting a key role for them in neuronal vulnerability to sCTOs. Consistently, depletion in gangliosides protected against sCTO toxicity. We hypothesize that the high content in lipid rafts makes mature neurons especially vulnerable to amyloid proteins, as compared to other cell types; this may help explain why the brain is a target organ for amyloid-related diseases.

Abstract Different pathogens cause different outcomes for patients with sepsis. They influence intensive care unit (ICU) mortality, ICU length of stay (ICU LOS) and the need for mechanical ventilation (MV). We undertook a retrospective data-based analysis over a 6-y period. Seventy-eight patients with methicillin-sensitive Staphylococcus aureus (MSSA) and 74 patients with Escherichia coli (EC) sepsis were included in the study. ICU mortality for the MSSA group was 32 (41.0%) vs 26 (35.1%) for the EC group (p = 0.506; OR 1.28, 95% CI 0.67-2.48). There was no significant difference in ICU LOS (MSSA group: median 7.5, interquartile range (IQR) 4-14 days and EC: median 5, IQR 3-13.5 days; p = 0.214). Need for MV in the MSSA group was present in 45 (57.7%) patients vs 43 (58.1%) in the EC group. Univariate analysis did not show that MSSA was independently associated with ICU mortality (p = 0.506). Logistic regression analysis showed that after adjustment for APACHE II, the chance of ICU death doubled in the MSSA group (odds ratio 2.166; 95% confidence interval 1.004-4.858). The odds for ICU admission were 8 times higher in MSSA patients. MSSA sepsis should be considered as an independent factor for ICU mortality after adjustment for APACHE II.

Aims Although an organizational model for syncope management facilities was proposed in the 2004 guidelines of the European Society of Cardiology (ESC), its implementation in clinical practice and its effectiveness are largely unknown. Methods and results This prospective study enrolled 941 consecutive patients referred to the Syncope Units of nine general hospitals from 15 March 2008 to 15 September 2008. A median of 15 patients per month were examined in each unit, but the five older units had a two-fold higher volume of activity than the four newer ones (instituted <1 year before): 23 vs. 12, P = 0.02. These figures give an estimated volume of 163 and 60 patients per 100 000 inhabitants per year, respectively. Referrals: 60% from out-of-hospital services, 11% immediate and 13% delayed referrals from the Emergency Department, and 16% hospitalized patients. A diagnosis was established on initial evaluation in 191 (21%) patients and early by means of 2.9 +/- 1.6 tests in 541 (61%) patients. A likely reflex cause was established in 67%, orthostatic hypotension in 4%, cardiac in 6% and non-syncopal in 5% of the cases. The cause of syncope remained unexplained in 159 (18%) patients, despite a mean of 3.5 +/- 1.8 tests per patient. These latter patients were older, more frequently had structural heart disease or electrocardiographic abnormalities, unpredictable onset of syncope due to the lack of prodromes, and higher OESIL and EGSIS risk scores than the other groups of patients. The mean costs of diagnostic evaluation was euro209 per outpatient and euro1073 per inpatient. The median cost of hospital stay was euro2990 per patient. Conclusion We documented the current practice of syncope management in specialized facilities that have adopted the management model proposed by the ESC. The results are useful for those who wish to replicate this model in other hospitals. Syncope remains unexplained during in-hospital evaluation in more complex cases at higher risk.

PURPOSE: We investigated the relationship among esophageal warming, pain perception, and the site of radiofrequency (RF) delivery in the left atrium (LA) during the course of catheter ablation of atrial fibrillation. Such a procedure in awake patients is often linked to the development of visceral pain and esophageal warming. As a consequence, potentially dangerous complications have been described. METHODS: Twenty patients undergoing RF ablation in the LA were studied. An esophageal probe (EP) capable of measuring endoesophageal temperature (ET) was positioned before starting the procedure. The relative position of the EP and the tip of the ablator were evaluated through fluoroscopy imaging before starting each RF delivery, during which the highest value of the temperature was collected. After RF withdrawal, the patients were asked to define the intensity of the experienced pain by using a score index ranging from 0 (no pain) to 4 (pain requiring immediate RF interruption). RESULTS: The mean ET value during ablation was 39.59 +/- 4.71 degrees C. The EP proximity to the ablator's tip showed a high correlation with the development of the highest ET values (Spearman's rank correlation coefficient r = 0.49, confidence interval (CI) 0.55-0.41). Moreover, the highest values of pain intensity were reported when the RF was delivered to the atrial zones close to the EP projection (r = 0.50, CI 0.55-0.42) and when the highest ET levels were reached (r = 0.38, CI 0.30-0.45). CONCLUSIONS: Pain perception in LA ablation is significantly related to esophageal warming and is higher when the RF is delivered near the esophagus. It seems advisable to perform ET monitoring in sedated patients to avoid short- and long-term jeopardizing of the esophageal wall.

Intrathoracic extramedullary hematopoiesis (EMH), the formation of apparently normal blood cells outside the confines of the bone marrow, is an uncommon but well-defined entity. It is usually associated with hematologic disorders and located in the lower paravertebral sulci or rarely in the pleura. We report a case of EMH, which presented in a patient without hematologic disorders and was manifested as an anterior mediastinal mass. The first interesting aspect of our case was that EMH occurred in a patient with normal laboratory findings and no past medical history of anemia. The second remarkable characteristic was that EMH manifested as an anterior mediastinal mass, mimicking a neoplastic lesion. Definitive diagnosis of EMH was established by a video-assisted thoracoscopic surgical biopsy. In light of this diagnosis, no further surgical procedure was carried out.

Background:Some implantable cardioverter defibrillators (ICD) are able to monitor intrathoracic impedance to detect pulmonary fluid overload. This is achieved by measuring impedance between the ICD case and the right ventricular (RV) lead. We hypothesized that the measured impedance would rise with improvement in left ventricular (LV) volumes during cardiac resynchronization therapy (CRT), and that such impedance changes would be more apparent when measured with an alternative pacing vector. Methods:We analyzed echocardiographic and impedance data from heart failure patients implanted with a CRT-ICD capable of intrathoracic impedance measurement for fluid accumulation diagnosis, and LV pacing impedance recording for lead integrity monitoring. Results:In 127 out of 170 patients that received de novo CRT implantation, the LV end-systolic volume (LVESV) decreased at 6-month follow-up (LVESV at 6 month-LVESV at baseline <0: group A). For the remaining 43 patients (group B) the change was >/=0. Despite comparable values at baseline (P = 0.262), the impedances of groups A and B gradually diverged soon after the implant, resulting in significant difference between the two groups at the 6-month visit (P = 0.001). The changes in LV dimensions produced larger differences between groups in the impedance measured between the LV and the RV leads (P < 0.001). The regression analysis demonstrated an inverse correlation between paired changes of volume and intrathoracic impedance. Higher correlation coefficient was obtained using the LV-to-RV measurement vector (r =-0.635, P < 0.001). Conclusions:The changes in ICD-measured impedance seem associated with the LV volume changes induced by CRT. Specifically, the LV-to-RV impedance estimations seem to better correlate with paired changes of ventricular volumes.(PACE 2009; 1-10).

A 48-year-old man with an episode of syncope and family history of sudden cardiac death was evaluated. The ECG showed negative T waves from V1 to V3 with evidence of epsilon-wave. Magnetic resonance imaging showed replacement with fibrofatty tissue in midapical regions of free wall of the right ventricle with dyskinesia. Transthoracic echocardiography revealed only mild enlargement of the middle right ventricular cavity. A programmed ventricular stimulation induced only an unsustained monomorphic ventricular tachycardia. Intracardiac echocardiography showed mild right ventricular enlargement and outflow dilatation (26 mm), microaneurysms with systolic bulging along the apical segment of the right ventricle. Bipolar voltage mapping, performed by the Carto system, detected a circumscribed low potential (<1.5 mV) area at the same level of the right ventricular apex. Cardiovascular imaging improves the detection of abnormal myocardial areas. Further studies are warranted to support this hypothesis.

BACKGROUND: The goal of our study was to molecularly dissect mesothelioma tumour pathways by mean of microarray technologies in order to identify new tumour biomarkers that could be used as early diagnostic markers and possibly as specific molecular therapeutic targets. METHODOLOGY: We performed Affymetrix HGU133A plus 2.0 microarray analysis, containing probes for about 39,000 human transcripts, comparing 9 human pleural mesotheliomas with 4 normal pleural specimens. Stringent statistical feature selection detected a set of differentially expressed genes that have been further evaluated to identify potential biomarkers to be used in early diagnostics. Selected genes were confirmed by RT-PCR. As reported by other mesothelioma profiling studies, most of genes are involved in G2/M transition. Our list contains several genes previously described as prognostic classifier. Furthermore, we found novel genes, never associated before to mesotheliom that could be involved in tumour progression. Notable is the identification of MMP-14, a member of matrix metalloproteinase family. In a cohort of 70 mesothelioma patients, we found by a multivariate Cox regression analysis, that the only parameter influencing overall survival was expression of MMP14. The calculated relative risk of death in MM patients with low MMP14 expression was significantly lower than patients with high MMp14 expression (P = 0.002). CONCLUSIONS: Based on the results provided, this molecule could be viewed as a new and effective therapeutic target to test for the cure of mesothelioma.