Home Monitoring in Patients with Implantable Cardiac Devices: Is There a Potential Reduction of Stroke Risk? Results from a Computer Model Tested Through Monte Carlo Simulations

Introduction: Patients with pacemakers and implantable defibrillators (ICD) may experience asymptomatic atrial fibrillation (AF), detected with a delay depending on the in-person follow-up schedule. Home monitoring (HM) remote control with automatic alerts for AF may drive early anticoagulation, potentially reducing stroke risk.
Methods and Results: A sample of 136 pacemaker (103) and ICD (33) patients with or without cardiac resynchronization therapy not taking anticoagulation at implant were monitored remotely with HM. Upon HM alerts for AF, patients were recalled to update therapy. Two-year data were entered in a computer Monte Carlo model, simulating 4,000 virtual subjects with the same AF and CHADS₂ stroke risk distribution of our real population. Simulations reproduced a 2-year follow-up. Two thousand subjects were supposed to be followed with HM (HM group) and 2,000 with standard in-person follow-up (SF group) at 3, 6, 9, or 12 months.
Two-year Kaplan-Meier cumulative probability of ≥24-hour AF was 15.6% (95%CI 8.5–23.3%); the AF-related symptom rate was 27% and the median CHADS₂ score was 2. As a result of simulations, stroke incidence in case of AF was 2.3 ± 1.1% in the HM group and 2.4 ± 1.1%, 2.5 ± 1.2%, 2.7 ± 1.2%, and 2.9 ± 1.3% in the SF group with 3-, 6-, 9-, and 12-month follow-up programs, with odds ratios of 0.97 (95%CI 0.93–1.01), 0.91 (0.88–0.95), 0.87 (0.84–0.90), and 0.82 (0.79–0.85) (HM better if odds ratios <1), respectively.
Conclusions: Daily HM potentially reduces the stroke risk by 9% to 18% with respect to SF with intervisit intervals of 6 to 12 months.     

Multigenetic lesions in infant acute leukaemias: correlations with ALL-1 gene status

The large majority of childhood B-precursor cell acute lymphoblastic leukaemia cases present IgH and TCRδ gene rearrangements. These rearrangements have been widely used as specific markers for monitoring minimal residual disease. However, their prognostic value still remains unclear. In order to determine whether IgH and TCRδ gene rearrangements have any influence on relapse and event-free survival (EFS), we analysed the clinical impact of these genetic characteristics in 51 B-precursor acute lymphoblastic leukaemia patients. 46/51 patients (90.2%) showed IgH gene rearrangements by Southern blot and/or polymerase chain reaction (PCR) analysis. No statistically significant associations were found between IgH gene rearrangement pattern and age, sex, WBC count, immunophenotype, risk factor, relapse or EFS. 27/41 patients (66%) showed Vδ₂Dδ₃ recombination by Southern blot and/or PCR analysis. At a median follow-up of 53 months the estimated 5-year EFS probability was 78 ± 3% for the whole group. The EFS probability among patients with a Vδ₂Dδ₃ recombination pattern in the TCRδ locus was 90 ± 3%, whereas for patients without Vδ₂Dδ₃ recombination was 39 ± 13% ( P  < 0.005).
IgH rearrangement patterns do not appear to influence relapse or EFS probability. However, TCRδ gene rearrangement patterns have a relevant impact on the relapse rate and the EFS probability. Patients with Vδ₂Dδ₃ recombination have better clinical outcome than patients without this recombination, independent of any other prognostic factors.     

Effect of inhaled histamine on occlusion pressure and breathing pattern in asthmatic patients

In animals, histamine inhalation is known to increase either respiratory frequency or respiratory drive by stimulation of airway vagal sensitive endings. However, it is not well known whether these changes are concomitant in man. In order to elucidate this point, we carried out the present investigation in thirty-five asthmatic patients who underwent bronchial provocation test by progressively doubling the dose of inhaled histamine. Bronchial reactivity to histamine allowed two populations of patients to be defined: group I with moderate and group II with mild, increased reactivity. In the twenty-three group I patients, neuromuscular inspiratory drive, assessed by mouth occlusion pressure (P_0.1), was found to be significantly increased while no significant changes in breathing pattern were noted. In the twelve group II patients histamine did not modify P_0.1 or breathing pattern. However, we were able to separate in group I a sub-group of ten patients, as with atopic asthma, in which histamine-induced increase in P_0.1 was paralleled by rapid and shallow breathing (RSB). Changes in P_0.1 and breathing pattern did not depend on baseline airway calibre. In group I, after bronchoconstriction had been reversed by inhaling a β₂-agonist bronchodilator agent (fenoterol), P_0.1 decreased significantly and RSB was found to be reversed; however, these changes were not interrelated. We concluded that: (i) in asthmatics, histamine-induced increase in P_0.1 is not necessarily paralleled by, nor related with, change in breathing pattern and (ii) in atopics a 'sensitization' of vagal receptors could account for the concomitance of enhanced P_0.1 with RSB.     

Study of Antisperm Antibodies Bound to the Sperm Cell Surface and Their Relationship to Circulating ASA

PROBLEM : Direct and indirect tests for antisperm antibody (ASA) detection are commonly used in laboratories for the diagnosis of male immunological infertility. Even though the two kinds of tests study the same immunological phenomena, frequently no perfect correlation is found even on large series of patients and with precise statistical models. The aim of the present investigation was to try to establish whether biological models can explain the antibody test results and if a predictive threshold can be established for expected positivity/negativity. METHOD : The data relate to 667 patients, who were screened using the Direct Immunobead test (d-IBT) for ASA bound to the sperm surface and with the gelatin and tray agglutination test (GAT and TAT) in sera for circulating ASA. Correlations were studied and cases of no correlation were further analyzed. RESULTS : The number of patients with a clinically significant positivity to d-IBT (binding percentage ≥ 20%) was 134 (20.1 % of total patients). The analysis of the results of direct and indirect tests shows that the discordances are due to differences in the Ig class of immunization or to the site of epitopes involved. In fact, as far the Ig class is concerned, if d-IBT shows a prevalent or exclusive IgG or IgA positivity, this results in a poor correlation between binding percentage to d-IBT and GAT-TAT titers. If both the Ig classes are involved, the level of positivity of the two kinds of test are strictly related. As far as the site of Ag-Ab reaction on the sperm surface is concerned, the wide immunization involving all the surface sperm antigens (mixed), shown by d-IBT, is related to higher indirect test titers. CONCLUSION : Local and systemic antisperm immunizations are strictly related and a predictive threshold of expectation can be established to explain even apparently discordant direct and indirect results.