Long-Term Survival in Patients Treated with Cardiac Resynchronization Therapy: A 3-Year Follow-Up Study from the InSync/InSync ICD Italian Registry

Background: Studies reporting the long-term survival of patients treated with cardiac resynchronization therapy (CRT) outside the realm of randomized controlled trials are still lacking. The aim of this study was to quantify the survival of patients treated with CRT in clinical practice and to investigate the long-term effects of CRT on clinical status and echocardiographic parameters.
Methods: The study population consisted of 317 consecutive patients with implanted CRT devices from eight Italian University/Teaching Hospitals. The patients were enrolled in a national observational registry and had a minimum follow-up of 2 years. A visit was performed in surviving patients and mortality data were obtained by hospital file review or direct telephone contact.
Results: During the study period, 83 (26%) patients died. The rate of all-cause mortality was significantly higher in ischemic than nonischemic patients (14% vs 8%, P = 0.002). Multivariate analysis showed that ischemic etiology (HR 1.72, CI 1.06–2.79; P = 0.028) and New York Heart Association (NYHA) class IV (HR 2.87, CI 1.24–6.64; P = 0.014) were the strongest predictors of all-cause mortality. The effects of CRT persisted at long-term follow-up (for at least 2 years) in terms of NYHA class improvement, increase of left ventricular ejection fraction, decrease of QRS duration (all P = 0.0001), and reduction of left ventricular end-diastolic and end-systolic diameters (P = 0.024 and P = 0.011, respectively).
Conclusions: During long-term (3 years) follow-up after CRT, total mortality rate was 10%/year. The outcome of ischemic patients was worse mainly due to a higher rate of death from progressive heart failure. Ischemic etiology along with NYHA class IV was identified as predictors of death. Benefits of CRT in terms of clinical function and echocardiographic parameters persisted at the time of long-term follow-up.     

Fourier Analysis in Patients with Different Pacing Modes

The purpose of this study was to evaluate the usefulness of phase analysis in detecting the altered activation sequence induced by different pacing modes. Radionuclide ventriculography and planar gated blood pool scintigraphy were performed at rest in 56 patients with different pacemakers. This method permitted us to localize the pacemaker impulse site in the right ventricle and its diffusion in the heart. In patients with VVI pacemaker, this technique showed an evident asynchronism of contraction and relaxation of each ventricle and the standard deviation of phase angle (sigma), calculated by computer, is greater during pacing than sinus rhythm for left (LV) and right (RV) ventricles (LV sigma: 17 degrees +/- 4 vs 11 degrees +/- 3, less than 0.001; RV sigma: 31 degrees +/- 7 vs 14 degrees +/- 4, P less than 0.001). In the patients with VVI rate responsive pacemakers, the LV sigma changed from 18.5 +/- 3 under pacing to 11 degrees +/- 3 in sinus rhythm, P less than 0.001, while the RV sigma changed from 30 degrees +/- 8 to 14 degrees +/- 4, P less than 0.001. Instead in the patients with DDD pacemakers, the LV sigma changed from 15.5 degrees +/- 2 under pacing to 11 degrees +/- 3 in sinus rhythm, P less than 0.05, while the RV sigma changed from 29.1 degrees +/- 6 to 14 degrees +/- 4, P less than 0.001.(ABSTRACT TRUNCATED AT 250 WORDS)     

Experience of maintenance infliximab therapy for refractory ulcerative colitis from six centres in England

Background  Infliximab is used for treatment of Crohn's disease and, following the Active Ulcerative Colitis Trials (ACT) 1 and 2, it has been used as rescue and maintenance therapy in moderate and severe ulcerative colitis (UC).
Aim  To report on English experience with maintenance infliximab in terms of response and colectomy rates and side-effect profile in UC.
Methods  A retrospective audit conducted by using a web-based questionnaire filled in by 12 gastroenterologists from six English centres.
Results  Of the 38 patients receiving induction with infliximab, 28 (73.6%) maintained an ongoing response (8-weekly infusions 5 mg/kg) for a mean duration of 16.8 months (range 4–59), with 21 (55.3%) being in remission. Three of 38 patients (7.9%) who also responded had a secondary loss of response after an average of 10 months (range 8–13); seven of 38 patients (18.4%) showed no response. The colectomy rate was seven of 38 (18.4%, five non-responders and two with secondary loss of response). Adverse effects occurred in five patients (13.2%). Two discontinued infliximab (alopecia, invasive breast cancer). The three less-severe adverse effects were acute and delayed-type hypersensitivity reactions and one persistent otitis media.
Conclusion  Our experience suggests acceptable response rates, colectomy rates and side-effect profile of maintenance therapy with infliximab in moderate and severe UC.     

The VITA Project: C677T mutation in the methylene-tetrahydrofolate reductase gene and risk of venous thromboembolism

We evaluated the hypothesis that a common polymorphism of the methylenetetrahydrofolate reductase gene (C677T), which results in increased levels of plasma homocysteine, may be a putative risk factor for venous thromboembolism (VT). Sixty-five cases of VT and 130 controls, both identified within the framework of an epidemiologic survey on thrombophilia, the Vicenza Thrombophilia and Arteriosclerosis (VITA) Project, were genotyped for the mutation. No increased risk of VT was found in carriers of the mutation. We conclude that screening for the C677T mutation of the methylenetetrahydrofolate reductase gene should not be recommended in unselected patients with VT.     

Longitudinal neuropsychological evaluation of HIV-infected intravenous drug users

The present study aimed to describe the cognitive status of a group of HIV-positive asymptomatic intravenous drug users (IVDU) and changes which occurred over a 12-month follow-up period. Forty-two HIV positive IVDU were selected and matched for age, sex, educational level and pattern of drug abuse with 39 seronegative IVDU controls. Baseline and follow-up evaluation included neuropsychological tests exploring attention, language, memory, logic and visuomotor abilities, biological markers and clinical parameters. About one-third of both seropositive and seronegative subjects showed at baseline slight cognitive deficits, ‘which did not change during the follow-up period.     

Liposomes as In-vivo Carriers for Citicoline: Effects on Rat Cerebral Post-ischaemic Reperfusion#

Abstract— Citicoline is a therapeutic agent widely used in the treatment of brain injury, for example in cerebrovascular disease or traumatic accidents. Unfortunately, the strong polar nature of this drug prevents it crossing the blood-brain barrier. In this paper, the possibility of efficiently trapping citicoline in liposomes to improve its therapeutic effects is reported. The citicoline-encapsulation efficiency, drug leakage and size analysis of various liposome systems were studied. The real therapeutic effectiveness of these citicoline liposome formulations was evaluated by biological assay. The effects of free and liposome encapsulated citicoline on survival rate of ischaemic reperfused male Wistar rats (80–100 g) were investigated. Of the phospholipid mixtures used in citicoline liposome formulation the best in terms of delivery and therapeutic effects was 1,2-dipalmitoyl-sn-glycero-phosphocholine:dipalmitoyl-dl -α-phosphatidyl-l -serine: cholesterol (7:4:7 molar ratio). This phospholipid mixture was also assayed for brain conjugated diene levels in rats, since this parameter is an index of lipid peroxidation in rat cerebral cortex during post-ischaemic reperfusion. A citicoline-loaded phospholipid mixture has produced an increase in rat survival rate of about 24% and a reduction in diene levels of 60%, compared to the free drug.