Cryoballoon ablation of atrial fibrillation is effectively feasible without previous imaging of pulmonary vein anatomy: insights from the 1STOP project.

BACKGROUND: Pulmonary vein isolation by cryoablation (PVI-C) is a standard therapy for the treatment of atrial fibrillation (AF); however, PVI-C can become a challenging procedure due to the anatomy of the left atrium and pulmonary veins (PVs). Importantly, the utility of imaging before the procedure is still unknown regarding the long-term clinical outcomes following PVI-C. The aim of the analysis is to evaluate the impact of imaging before PVI-C on procedural data and AF recurrence. METHODS: Patients with paroxysmal AF underwent an index PVI-C. Data were collected prospectively in the framework of 1STOP ClinicalService® project. Patients were divided into two groups according to the utilization of pre-procedural imaging of PV anatomy (via CT or MRI) or the non-usage of pre-procedural imaging. RESULTS: Out of 912 patients, 461 (50.5%) were evaluated with CT or MRI before the PVI-C and denoted as the imaging group. Accordingly, 451 (49.5%) patients had no pre-procedural imaging and were categorized as the no imaging group. Patient baseline characteristics were comparable between the two cohorts, but the ablation centers that comprised the imaging group had fewer PVI-C cases per year than the no imaging group (p < 0.001). The procedure, fluoroscopy, and left atrial dwell times were significantly shorter in the no imaging cohort (p < 0.001). The rates of complications were significantly greater in the imaging group compared to the no imaging group (6.9% vs. 2.7%; p = 0.003); this difference was attributed to differences in transient diaphragmatic paralysis. The 12-month freedom from AF was 76.2% in the imaging group and 80.0% in the no imaging group (p = 0.390). CONCLUSIONS: In our analysis, PVI-C was effective regardless of the availability of imaging data on PV anatomy.

Long-term survival, prevalence, and cure of cancer: a population-based estimation for 818 902 Italian patients and 26 cancer types.

BACKGROUND: Persons living after a cancer diagnosis represent 4% of the whole population in high-income countries. The aim of the study was to provide estimates of indicators of long-term survival and cure for 26 cancer types, presently lacking. PATIENTS AND METHODS: Data on 818 902 Italian cancer patients diagnosed at age 15-74 years in 1985-2005 were included. Proportions of patients with the same death rates of the general population (cure fractions) and those of prevalent patients who were not at risk of dying as a result of cancer (cure prevalence) were calculated, using validated mixture cure models, by cancer type, sex, and age group. We also estimated complete prevalence, conditional relative survival (CRS), time to reach 5- and 10-year CRS >95%, and proportion of patients living longer than those thresholds. RESULTS: The cure fractions ranged from >90% for patients aged <45 years with thyroid and testis cancers to <10% for liver and pancreatic cancers of all ages. Five- or 10-year CRS >95% were both reached in <10 years by patients with cancers of the stomach, colon-rectum, pancreas, corpus and cervix uteri, brain, and Hodgkin lymphoma. For breast cancer patients, 5- and 10-year CRSs reached >95% after 19 and 25 years, respectively, and in 15 and 18 years for prostate cancer patients. Five-year CRS remained <95% for >25 years after cancer diagnosis in patients with liver and larynx cancers, non-Hodgkin lymphoma, myeloma, and leukaemia. Overall, the cure prevalence was 67% for men and 77% for women. Therefore, 21% of male and 31% of female patients had already reached 5-year CRS >95%, whereas 18% and 25% had reached 10-year CRS >95%. CONCLUSIONS: A quarter of Italian cancer patients can be considered cured. This observation has a high potential impact on health planning, clinical practice, and patients' perspective.

Molecular systematics of the Simulium jenningsi species group (Diptera: Simuliidae), with three new fast-evolving nuclear genes for phylogenetic inference.

A molecular phylogeny was inferred for the 22 nominal species of black flies in the Simulium jenningsi species group, which includes major pests of humans and livestock in North America. Females are structurally monomorphic, presenting a problem for identification of the pests. For each species, we sequenced approximately two kilobases from the mitochondrial genome (ND2, Cox I, proximal one-half of Cox II) and about six kilobases from the nuclear genome (ca. 2 kilobases each from 3 rapidly evolving nuclear genes: big zinc finger [BZF], "5-intron gene" [5intG], and elongation complex protein 1 [ECP1]) and analyzed them phylogenetically using maximum likelihood and Bayesian methods. The three nuclear loci have not previously been used in phylogenetic studies. The mitochondrial region recovered 6 group members as monophyletic. BZF, 5intG, and ECP1 sequences each permitted identification of 13 species and recovered the S. fibrinflatum and S. taxodium subgroups. Simulium aranti Stone and Snoddy and S. luggeri Nicholson and Mickel were consistently recovered at the base of the group. Simulium ozarkense Moulton and Adler, S. dixiense Stone and Snoddy, S. krebsorum Moulton and Adler, and S. haysi Stone and Snoddy branched off before two well-supported sister groups of the remaining species. This remainder consisted of species occupying slow, sandy lowland streams-S. definitum Moulton and Adler, S. jonesi Stone and Snoddy, and the S. taxodium subgroup (S. taxodium Snoddy and Beshear, S. chlorum Moulton and Adler, S. confusum Moulton and Adler, and S. lakei Snoddy)-as sister to two clades of species inhabiting swift, rocky upland streams-the S. fibrinflatum subgroup (S. fibrinflatum Twinn, S. notiale Stone and Snoddy, and S. snowi Stone and Snoddy) and a clade comprised of S. anchistinum Moulton and Adler, S. jenningsi Malloch, and S. nyssa Stone and Snoddy, plus species having cocoons without anterolateral apertures (S. infenestrum Moulton and Adler, S. podostemi Snoddy, S. penobscotense Snoddy and Bauer, and S. remissum Moulton and Adler). Simulium snowi Stone and Snoddy is here considered a synonym of S. notiale Stone and Snoddy. Trees inferred from BZF and 5intG were largely concordant with those from ECP1, but slightly less resolved. Combining mitochondrial and nuclear data sets did not greatly improve the performance of the ECP1 data set alone. We, therefore, propose ECP1 as the gold standard for identification of members of the S. jenningsi group. Maximum likelihood analysis of combined sequences from all three nuclear genes, with three morphological constraints imposed, yielded a tree proposed as the best hypothesis of relationships among group members, based on all available data.

[Ectopic breast fibroadenoma. Case report]. / Fibroadenoma in mammella ectopica. Case report.

Among the rare anomalies of the breast development, polythelia is the most common, between 1% and 5% of women and men present supernumerary nipples. Polymastia, usually presenting as ectopic breast tissue without areola-nipple complex, is seen mostly along the milk line, extending from the axilla to the pubic region. Ectopic breast tissue is functionally analogous to mammary gland and it is subjected to the same alterations and diseases, whether benign or malignant, that affect normal breast tissue. We report the case of a 21 years-old female evaluated by the medical staff after founding a solid nodular mass by suspect axillary lymphadenopathy. Differential diagnosis with lymphoma is the major problem in these cases. The mass was removed and the intraoperative histological examination showed fibroadenoma in axillary supernumerary breast. Presence of ectopic breast tissue is a rare condition; development of benign mass or malignant degeneration is possible, but it is very unusual. In case of polymastia diagnosis is simple; in case of isolated nodule, without local inflammation or infection, there are greater difficulties. Ultrasonography is diagnostic in case of breast fibroadenoma, but it might be inadequate in ectopic localizations owing to the shortage of mammary tissue around the mass. Preoperative diagnosis is important to plan an adequate surgical treatment; lumpectomy is indicated in case of benign tissue; in case of malignancy, therapy is based on the standard treatment used for breast cancer (surgery, chemotherapy and radiation therapy).

Sarcomatoid anaplastic carcinoma of the small bowel in cardiac transplant bearer.

Sarcomatoid carcinoma is a rare form of primitive carcinoma of the small bowel; it is considered a variant of adenocarcinoma, histologically characterized by a typical biphasic pattern with epithelial- and mesenchymal-like cells. Twenty-one cases have been described in the literature, presenting as small bowel obstructions (twenty cases) or superior vena cava syndrome (one case). The authors report the case of a 56 year-old man on immunosuppressive therapy for a heart transplant, who underwent surgery after a history of repeated episodes of melena, anemization and bowel obstruction. The operation brought to light an intraluminal occlusive mass in the distal ileum, associated with other intraluminal neoplasms of different sizes throughout the small bowel. No evidence of mesenteric adenopathies or hepatic metastases were found. Histological examination and immunohistochemical stain showed an anaplastic sarcomatoid carcinoma. The tumor cells showed strong positivity for cytokeratin and vimentin, and negativity for CD117 and CD34, as well as for all other characteristic markers of mesenchymal tumors. Early diagnosis is usually very difficult, due to the lack of any stereotyped clinical expression and the difficult to study the small bowel. Small-bowel barium follow-through or video capsule endoscopy can be helpful. In most cases, an emergency surgical operation is performed without a clear preoperative diagnosis. The case report is completed by a review of the literature.

Determinants of efficacy of atrial pacing in preventing atrial fibrillation recurrences.

INTRODUCTION: Several studies have shown that single or dual site atrial pacing is effective in reducing the frequency of recurrent atrial fibrillation (AF) in selected patients. However, it is still unclear what the best predictors are of long-term efficacy of atrial pacing. METHODS AND RESULTS: Forty-seven patients with paroxysmal AF requiring demand pacing underwent electrophysiologic study and dual chamber pacemaker implant. After 4 months of follow-up, patients were divided into two groups according to the presence (group 1) or absence (group 2) of symptomatic AF recurrences. Atrial pacing markedly reduced AF recurrences in all patients. Twenty-four patients were free of arrhythmia. The basal state conduction times (CTs) and the incremental conduction times (ICTs), during programmed electric stimulation between the high right atrium (HRA) and the coronary sinus ostium (CSos), but not between the HRA and the His-bundle region, were significantly longer in group 1. There was no statistical difference in the effective refractory period (ERP) recorded at the HRA, the low right atrium (LRA), and the CSos between the two groups, whereas the differences between the greatest and least recorded ERPs measured from the HRA, LRA, and CSos (deltaERP) were significantly greater in group 1 patients. Two parameters were selected by discriminant multivariate analysis, namely deltaCTos (ICT-CT between HRA and CSos) and deltaERP. The first had a greater relative importance in predicting AF recurrence (r2 = 0.33 and r2 = 0.1, respectively). CONCLUSION: Single site atrial pacing is effective in reducing AF recurrences, with decreasing efficacy in patients with greater right atrial conduction delay and wider refractoriness dispersion.

Feasibility and safety of two French electrode catheters in the performance of electrophysiological studies.

UNLABELLED: The aim of this study was to analyze prospectively the feasibility and safety of using 2 Fr versus 6 Fr standard electrode catheters for diagnostic electrophysiological study. METHODS: Two hundred and five consecutive patients were randomized to receive the 6 Fr approach (3 quadripolar, 6 Fr, electrode catheters inserted through the left or right femoral vein and placed in the high right atrium, right ventricular apex, and His bundle area) or the 2 Fr approach (3 quadripolar, 2 Fr, electrode catheters inserted through a single, 7 Fr, triple lumen, guiding catheter and positioned at the same sites as the 6 Fr approach). RESULTS: Introduction time was shorter in the 2 Fr group (133.3 +/- 65 s, range 87-669 s) than in the 6 Fr group (242.8 +/- 91.8 s, range 168-1024 s, P < 0.001). The overall fluoroscopy time was longer in the 2 Fr group (141.2 +/- 40.1 s, range 78-312 s) than in the 6 Fr group (126.4 +/- 39.7 s, range 58-341 s, P = 0.009). However in the last 100 patients there was no more difference between the two groups (137.6 +/- 28.2 s vs 128.4 +/- 23.2 s, P = 0.07). There was no significant difference between 2 Fr and 6 Fr groups in the mean atrial (5.9 +/- 2.2 mV, range 2.2-11.3 mV, vs 6.1 +/- 2.3 mV, range 2.4-12.4 mV, P = 0.57) and ventricular (5.6 +/- 2.1 mV, range 1.9-9.7 mV, vs 5.7 +/- 2.2 mV, range 2.3-10.5 mV, P = 0.66) activation potential amplitudes recorded during sinus rhythm, or in the rate of stable His bundle potential recording (P = 0.3), and catheter dislodgment (P = 0.54). The overall number of complications was significantly higher in the 6 Fr group than in the 2 Fr group (29 vs 5, P = 0.001), as well as the number of entry site related complications (3 vs 12, P = 0.02) and catheter manipulation related complications (2 vs 17, P < 0.001). CONCLUSIONS: The results of this study show that the use of 2 Fr electrode catheters reduces the rates of entry site and catheter manipulation related complications during EPS. Despite their small size, these catheters allow quick and precise positioning of the electrode.

[Computerized follow-up cards for ambulatory patients with implanted pacemaker or defibrillator]. / La carta sanitaria informatizzata nella gestione ambulatoriale del paziente con pacemaker o defibrillatore impiantabile.

The follow up of pacemaker and defibrillator dependent patients has a significant role for both the evaluation of pacing effectiveness and check of hemodynamic advantages about patient's quality of life. The bulky paper archives are often inaccurate, hampering the consultation. At present the paper card is the only document which can be utilized to record some data concerning the implant and patient clinical story. Therefore, there is the necessity for a card that can include all patient's data, and the implant and programming pacemaker/defibrillator data during follow up. This new pacemaker card has portable file or data-base including shared data with safety mechanism, which can be utilized in several controls by different users (physicians, hospital ward, primary care units, insurance companies). The pacemaker card includes a chip that permits to store a considerable amount of data; it can be update in every further medical control, in observance of laws. The card Chip Operating System (C.O.S.) consists of a microchip with a memory completely managed by the operating system inside the chip itself. The card can be read by means of a GCR-200 modem linked with a PC IBM-compatible computer and the data can be updated during the follow up. The pacemaker-defibrillator card will appear immediately on screen, and it can be printed, updated and/or modified by a Microsoft Windows operating programme. With this pacemaker card we are able to ensure serviceable medical work, particularly in terms of cost/benefit ratio giving to patient more and more reasoning and safe service.

1,2,3-Triazolo [4,5-d] pyridazines--V. Preparation and adenosine receptor binding of new 4-amino derivatives.

This paper reports the continuation of studies on the 4-aminosubstituted 1,2,3-triazolo [4,5-d] pyridazine derivatives which had shown binding affinity towards A1-adenosine receptors. 1-Benzyl derivatives bearing new amines and new 1-(substituted benzyl) derivatives were prepared and tested. The biological results showed that some compounds possessed high affinity (approximately 30-70 nM) and good selectivity toward the A1-adenosine receptors. Further information about structure-biological activity relationships was aquired.

Role of catheter-induced mechanical trauma in localization of target sites of radiofrequency ablation in automatic atrial tachycardia.

OBJECTIVES: We compared the efficacy of two different mapping techniques in identifying the ablation site for atrial tachycardia. Moreover, we evaluated the additive positive predictive value of mechanical interruption of atrial tachycardia to reduce the number of ineffective radiofrequency applications. BACKGROUND: Radiofrequency catheter ablation has been suggested as a highly effective technique to treat drug-resistant atrial tachycardia. However, irrespective of the mapping technique utilized, success was most often achieved with a large number of radiofrequency applications. METHODS: Forty-five patients with atrial tachycardia underwent radiofrequency catheter ablation. Mapping techniques included identification of earliest atrial activation and pace-mapping concordant sequence. RESULTS: Atrial tachycardia was successfully treated in 42 (93.3%) of 45 patients with a mean of 3.9 radiofrequency pulses/patient. An interval between the onset of the intracavitary atrial deflection and the onset of the P wave during atrial tachycardia (AP interval) > or = 30 ms (p < 0.001) and pace-mapping concordant sequence (p = 0.01) were all significant predictors of outcome. An AP interval > or = 30 ms and a pace-mapping concordant sequence were highly sensitive (92.8%, 95% confidence interval [CI] 80.5% to 98.5%; 85.7%, 95% CI 71.5% to 94.6%, respectively) but less specific (47.8%, 95% CI 37.9% to 58.2%, 36.8%, 95% CI 27.6% to 47.2%, respectively) in identifying the site of ablation. By using atrial tachycardia mechanical interruption combined with the AP interval >30 ms or the pace-mapping concordant sequence, we obtained a specifically of 76.5% (95% CI 66.4% to 84.0%) and 73.5% (95% CI 63.2% to 81.4%), respectively, and a positive predictive value of 49.2% and 44.6%, respectively. CONCLUSIONS: An AP interval > or = 30 ms and a pace-mapping concordant sequence were reliable mapping features for predicting the outcome of the ablation procedure. Mechanical interruption of atrial tachycardia improved the specificity and positive predictive value of these two mapping techniques.

1,2,3-triazolo[1.5-a]quinazolines: synthesis, benzodiazepine receptor binding and theoretical calculations.

This paper reports the synthesis of 3-substituted-1,2,3-triazolo[1,5-a]quinazolin-5-ones prepared by 1,3-dipolar cycloaddition reaction of 2-azidobenzoic acid to methylenic compounds activated by a cyano group. The new derivatives were submitted to benzodiazepine receptor binding assays: the results indicated an interesting receptorial affinity of the 1,2,3-triazolo[1,5-a]quinazoline ring. On the basis of the biological results, theoretical calculations were performed, which suggested useful structural modifications.

[Radiofrequency catheter ablation of atrial tachycardia: technique, results and follow-up]. / Ablazione transcatetere mediante radiofrequenza di tachicardia atriale: tecnica, risultati e follow-up.

BACKGROUND: Recently radiofrequency (RF) catheter ablation (CA) of atrial tachycardia (AT) showed to be highly effective with a low incidence of compliance. Aim of our study was to report the results and follow-up of RFCA of drug-refractory AT in 59 consecutive patients (pts). METHODS: Two mapping techniques were used to localize the ablation site of AT: the earliest atrial activation and the pace-mapping. Traumatic interruption of AT was used to verify the ablation site identified by the previous procedures. Moreover we evaluated the sensitivity, specificity and the positive predictive value of the three mapping techniques. RESULTS: AT was successfully treated in 55/59 (93.2%) pts with a mean of 4.0 +/- 3.8 (range 1-16) RF pulses for patient. The mean procedure time was 185.2 +/- 48.5 min with a mean rx-time of 41.5 +/- 21.3 min. An interval between the onset of the intracavitary atrial deflection and the onset of the P-wave, during atrial tachycardia, (AP interval) > or = 30 ms and pace-mapping concordant sequence were highly sensitive (90.9% and 89.1%) but less specific (49.2% and 33.9%) in identifying the site of ablation. By using atrial tachycardia traumatic interruption combined with the AP interval > 30 ms or the pace-mapping concordant sequence we obtained a specificity of 78.7% and 77.0% respectively and a positive predictive value of 48.0% and 46.8% respectively. Four recurrences (7.3%) were observed during a mean follow-up of 23.4 +/- 13.3 months. In the 22 (37.3%) pts with dilated cardiomyopathy, chest Xr and echocardiography showed a significant decrease of cardiothoracic index (0.56 +/- 0.08 pre ablation, 0.43 +/- 0.07 post ablation, p < 0.001) and end-diastolic diameter (64 +/- 8 mm pre ablation, 52 +/- 8 mm post ablation, p < 0.001) and a significant improvement of left ventricular ejection fraction (37 +/- 9% pre ablation, 48 +/- 11% post ablation, p < 0.05). CONCLUSION: The RFCA of AT was effective and safe. Moreover we observed a hemodynamic improvement in patients with reduced ejection fraction and increased cardiac volumes. An AP interval > or = 30 ms and the pace-mapping concordant sequence were reliable features to predict the outcome of the ablation procedure. Traumatic ablation of atrial tachycardia improved the specificity and the positive predictive value of these two mapping techniques and was able to predict the response to radiofrequency with a high specificity.

Structure-activity relationships in a series of 8-substituted xanthines as bronchodilator and A1-adenosine receptor antagonists.

Four new derivatives of 8-piperazine ethyl xanthine were synthesized and their bronchospasmolytic activity and A1-adenosine affinity were studied. Their relaxant action in the tracheal muscle was lower than that of theophylline and that of theophylline derivatives substituted at the 7-position. Only compound 9, where the methyl group in the 1-position of the theophylline was substituted by an isobutyl group, shows a good affinity towards the A1-adenosine receptor.

Synthesis of 3-(2'-furoyl)indole derivatives as potential new ligands at the benzodiazepine receptor, structurally more restrained analogues of indoleglyoxylylamides.

A number of furoylindoles were synthesized with the aim of obtaining structurally more restrained analogues of the previously described indoleglyoxylylamides, which are high affinity ligands at the benzodiazepine receptor. In these new compounds, the oxygen atom of the oxalyl CO(2) is inserted into the rigid furan ring. However, unlike the glyoxylylamides, they proved to be incapable of interacting with the benzodiazepine receptor. To rationalize these results, molecular electrostatic potentials were calculated; these indicated a positive electrostatic potential region for the furan oxygen, which thus prevents the formation of a hydrogen bond necessary for interaction with the receptor. Nevertheless, these findings confirmed that the CO(2) of the indoleglyoxylylamide derivatives represents one of the principal points of interaction with the receptor site for these kinds of ligands, as previously hypothesized by us.

1,2,3-triazole[4,5-d]pyridazines--IV. Preparation and adenosine receptor binding of new 4 and/or 7 aminoderivatives.

This paper reports the continuation of the studies on the 4-aminosubstituted 1,2,3-triazole[4,5-d]pyridazine derivatives which had shown binding affinity towards adenosine receptors. Biological results confirmed the greater activity of a benzyl substituent in the 1 position and the receptorial stereoselectivity related to the higher and more selective A1 affinity of the 4-D(+)-alpha-methylbenzylamino enantiomer 1b. The 4-phenylhydrazino substituent has shown an interesting binding activity about equipotent towards A1 and A2 receptorial sites. A surprisingly elevated A1 affinity (Ki = 7 nM), 440 fold higher than A2 affinity, is presented by compound 1d, bearing a m-toluidino substituent.

N-(indol-3-ylglyoxylyl)amino acid ester derivatives. Synthesis and interaction properties at the benzodiazepine receptor.

Several N-(indol-3-ylglyoxylyl)alanine and glycine ester derivatives were prepared to evaluate the influence of the ester group size both on affinity and on activity at the benzodiazepine receptor. Moreover, indol-3-ylglyoxylic acid esters, closely related to 3-alkoxy-beta-carbolines, were synthesized and tested in vitro on the benzodiazepine receptor.