New film‐coated tablet formulation of deferasirox is well tolerated in patients with thalassemia or lower‐risk MDS: Results of the randomized,phase II ECLIPSE study

Once‐daily deferasirox dispersible tablets (DT) have a well‐defined safety and efficacy profile and, compared with parenteral deferoxamine, provide greater patient adherence, satisfaction, and quality of life. However, barriers still exist to optimal adherence, including gastrointestinal tolerability and palatability, leading to development of a new film‐coated tablet (FCT) formulation that can be swallowed with a light meal, without the need to disperse into a suspension prior to consumption. The randomized, open‐label, phase II ECLIPSE study evaluated the safety of deferasirox DT and FCT formulations over 24 weeks in chelation‐naïve or pre‐treated patients aged ≥10 years, with transfusion‐dependent thalassemia or IPSS‐R very‐low‐, low‐, or intermediate‐risk myelodysplastic syndromes. One hundred seventy‐three patients were randomized 1:1 to DT (n = 86) or FCT (n = 87). Adverse events (overall), consistent with the known deferasirox safety profile, were reported in similar proportions of patients for each formulation (DT 89.5%; FCT 89.7%), with a lower frequency of severe events observed in patients receiving FCT (19.5% vs. 25.6% DT). Laboratory parameters (serum creatinine, creatinine clearance, alanine aminotransferase, aspartate aminotransferase and urine protein/creatinine ratio) generally remained stable throughout the study. Patient‐reported outcomes showed greater adherence and satisfaction, better palatability and fewer concerns with FCT than DT. Treatment compliance by pill count was higher with FCT (92.9%) than with DT (85.3%). This analysis suggests deferasirox FCT offers an improved formulation with enhanced patient satisfaction, which may improve adherence, thereby reducing frequency and severity of iron overload‐related complications.     

Epidemiological study of tick-borne encephalitis virus in northern Greece

Serum samples from 921 apparently healthy individuals living in different prefectures of Northern Greece were investigated for the presence of antibodies against tick-borne encephalitis (TBE) virus. In addition, serum and cerebrospinal fluid samples of 302 patients with central nervous system (CNS) infection were tested for the presence of specific IgG and IgM antibodies and TBE virus RNA. Two percent of the general population was found to have antibodies to the virus, with no significant differences among the age groups. Most of the seropositive individuals were male farmers, while seroprevalence varied among different prefectures (0%-5.8%). TBE was not confirmed by laboratory findings in any of the patients with CNS infection. Results of this study revealed that a flavivirus of the TBE serocomplex is circulating in Greece, yet is not a major public health problem.     

Radiofrequency Ablation in Older Children and Adolescents by an Adult Electrophysiology Team

Background: Radiofrequency (RF) catheter ablation has been widely and successfully employed to cure adult patients of a variety of arrhythmias. Only a few centers have a pediatric electrophysiology (EP) service available and have presented similar results in children. The aim of this study was to investigate the efficacy and safety of RF ablation in pediatric patients performed by an adult EP team.Patients and Methods. The study group included 33 consecutive pediatric patients, aged 7–18 years (mean 14.1±3.1), with symptomatic supraventricular tachyarrhythmias, who underwent RF ablation during the last 3 years. All but two patients underwent a full EP study during the same session. Procedures were performed in all but five patients with use of local anesthesia and deep or light sedation. The left heart was approached with use of transaortic (n = 3) or transseptal (n = 7) techniques. RF ablation was performed for manifest (n = 11) or concealed (n = 9) (9 left, 4 anteroseptal, 3 midseptal, and 4 posteroseptal) or right atriofascicular (Mahaim) (n = 1) accessory pathways in 19 patients, 12 slow AV nodal pathways and 2 atrial tachycardia foci in the other 14 patients.Results. RF ablation was successful in all patients (100%) with 1–27 RF applications (mean: 10±7). There was one complication in a patient with 2 accessory pathways; after RF ablation of a posteroseptal accessory pathway, complete heart block occurred during successful ablation of a second midseptal accessory pathway. Fluoroscopy time averaged 35±23 min and procedure duration 2.8±1.4 hours. During long-term follow-up of 19±10 months, there was one AV nodal tachycardia recurrence at 2.5 months, successfully treated with repeat RF ablation.Conclusion. RF ablation in pediatric patients performed by an adult EP team is efficacious and safe offering cure of symptomatic cardiac tachyarrhythmias in this patient population.     

Abnormal signal-averaged electrocardiograms in patients with incomplete right bundle-branch block

Background and hypothesis: A hypothesis was formulated that regional delayed activation of the right ventricle, as seen in incomplete right bundle-branch (IRBBB) aberrancy, may simulate late potential activity and may be responsible for abnormal signal-averaged electrocardiograms (SAECGs). No previous studies have specifically addressed this issue in this particular group of patients (with IRBBB). Therefore, the aim of the present study was to investigate the incidence of abnormal SAECGs in patients with IRBBB. If this were confirmed, our purpose would further be to investigate ways of reducing the false positive results. Methods: The study group included 53 patients (28 men and 25 women), aged 53 ± 13 years, with no history of previous myocardial infarction or ventricular tachycardia and who had an electrocardiogram (ECG) showing IRBBB. An SAECG was also performed in a control group of 19 age-matched individuals with a normal ECG. Time domain analysis was performed using a band pass filter of 40–250 Hz. The following parameters were considered normal: filtered QRS duration (QRSD) < 114 ms, root mean square of the voltage of the last 40 ms of the QRS complex (RMS) > 20 μV, and the duration of the low amplitude signal (< 40 μV) at the terminal portion of the QRS (LAS) < 38 ms. An SAECG was considered abnormal if any two of these criteria were abnormal. Results: The mean values of the SAECG parameters were: QRSD 101 ± 11 ms, RMS 32 ± 20 μV, LAS 32 ± 12 ms, and noise 0.29 ± 0.13 μV. Abnormal SAECGs with at least two criteria satisfied were present in 16 of 53 (30%) patients compared with 0 (0%) of 19 individuals in the control group (p = 0.02). Abnormal values included the combination of RMS and LAS in 12 patients and all three parameters in 4 patients. However, if the definition of late potentials were limited to the combination of abnormal QRSD and either RMS or LAS values, the incidence of false positive results (4 patients) (7.5%) would be significantly decreased (p = 0.007). At 21 months of follow-up, no arrhythmic events occurred. Conclusions: Delayed terminal conduction observed in IRBBB may cause a high incidence of false positive late potentials on SAECGs. Based on this study, we propose that this can be largely remedied if the optimal criteria for the presence of late potentials in patients with IRBBB always include the combination of QRSD and either RMS or LAS.     

Association of leptin -2548G/A and leptin receptor Q223R polymorphisms with increased risk for oral cancer

Purpose  We investigated the possible association of DNA polymorphisms −2548G/A and Q223R in the leptin (LEP) and leptin receptor (LEPR) genes, respectively, which both affect the amount of circulating cytokine-type hormone leptin, with risk for development of oral cancer. Methods  Polymerase chain reaction-based restriction analysis was performed in DNA samples of 150 patients with oral squamous cell carcinoma (OSCC) and 152 healthy control subjects of equivalent gender, age, and ethnicity (Greeks and Germans). Results  Compared to controls, the homozygous high gene expression genotype A/A of the LEP −2548G/A polymorphism was significantly increased in the subgroups of patients with advanced cancer stages (P = 0.0001; OR 9.0, 95% CI 2.62–30.89), with a positive family history of cancer (P = 0.0346; OR 3.55, 95% CI 1.15–11.01), without tobacco abuse (P = 0.0051; OR 9.69, 95% CI 1.03–91.24), and without alcohol abuse (P = 0.0472; OR 2.16, 95% CI 0.87–5.37). The homozygous low-leptin-binding genotype G/G of the LEPR Q223R polymorphism was strongly associated with an increased risk for OSCC for all patients (P = 0.0028; OR 4.11, 95% CI 1.30–12.97) as well for most of the patient subgroups. Conclusions  The above findings are consistent with the growth-promoting role of leptin in cancer and its induction effect on angiogenesis and metastasis. This is the first study indicating the association of these LEP and LEPR gene polymorphisms with increased risk for OSCC.     

Current approach to iron chelation in children

Transfusion‐dependent children, mostly with thalassaemia major, but also and occasionally to a more significant degree, with inherited bone marrow failures, can develop severe iron overload in early life. Moreover, chronic conditions associated with ineffective erythropoiesis, such as non‐transfusion‐dependent thalassaemia (NTDT), may lead to iron overload through increased gut absorption of iron starting in childhood. Currently, the goal of iron chelation has shifted from treating iron overload to preventing iron accumulation and iron‐induced end‐organ complications, in order to achieve a normal pattern of complication‐free survival and of quality of life. New chelation options increase the likelihood of achieving these goals. Timely initiation, close monitoring and continuous adjustment are the cornerstones of optimal chelation therapy in children, who have a higher transfusional requirements compared to adults in order to reach haemoglobin levels adequate for normal growth and development. Despite increased knowledge, there are still uncertainties about the level of body iron at which iron chelation therapy should be started and about the appropriate degree of iron stores’ depletion.     

Increased response of diastolic blood pressure to exercise in patients with coronary artery disease: an index of latent ventricular dysfunction?

OBJECTIVE--To determine whether an abnormal response of diastolic blood pressure during treadmill exercise stress testing correlated with the number of obstructed vessels and with left ventricular systolic function in patients with coronary artery disease. DESIGN--Diastolic blood pressure was measured invasively during exercise stress testing and coronary angiograms and left ventriculograms were obtained at rest in patients with coronary artery disease. The abnormal (> or = 15 mm Hg) diastolic blood pressure response was compared with the number of obstructed coronary arteries and with left ventricular systolic function. SETTING--Two tertiary referral centres. PATIENTS--50 consecutive patients (mean age 57 years) with coronary artery disease. MAIN OUTCOME MEASURES--The increase in diastolic blood pressure during exercise and its correlation with the appearance and disappearance of ST segment deviation, resting left ventricular systolic function, and the number of obstructed coronary arteries. RESULTS--Group 1: 10 (20%) patients (three with one, four with two, and three with three vessel coronary artery disease) (mean (SD) age 54.7 (12) years) had an abnormal diastolic blood pressure response that appeared 1.2 (0.3) min before ST segment deviation and became normal 0.9 (0.3) min after the ST segment returned to normal. Group 2: 40 (80%) patients (12 with one, 16 with two, and 12 with three vessel coronary arteries disease) (aged 56.8 (8.2) years) had a normal diastolic blood pressure response to stress testing. The ejection fraction (46.3 (5)%) and cardiac index (2.6 (0.1) 1/min/m2) in group 1 were less than in group 2 (61.6 (4.2)% and 3.8 (0.3) 1/min/m2 respectively, p < or = 0.001). The end systolic volume was greater in group 1 than in group 2: 38.7 (0.7 ml/m2 v 28.2 (2.1) ml/m2, p < or = 0.001. CONCLUSION--In patients with coronary artery disease an abnormal increase in diastolic blood pressure during exercise stress testing correlated well with left ventricular systolic function at rest but not with the number of obstructed coronary arteries. The abnormal response of diastolic blood pressure probably reflects deterioration of myocardial function.     

Correction for Heart Rate Is Not Necessary for QT Dispersion in Individuals without Structural Heart Disease and Patients with Ventricular Tachycardia

Background: It remains controversial whether QT dispersion should be corrected for heart rate, especially when the limitations of rate correction formulae are considered. We investigated whether incremental atrial pacing affects QT dispersion and the rate‐corrected values according to Bazett's formula in individuals without structural heart disease and in patients with history of sustained ventricular tachycardia. Methods: We studied 32 individuals without structural heart disease (group A), and 16 patients with a history of sustained ventricular tachycardia (group B). QT dispersion and corrected for heart rate QT dispersion using Bazett's formula (QTc dispersion) were calculated in sinus rhythm, and during continuous right atrial pacing for one minute at 100 and 120 beats/min. Results: Interobserver variability was not significant (P ≧ 0.10). QT dispersion did not differ at rest between groups A and B and did not change significantly from baseline at any heart rate in both groups. However, QTc dispersion increased significantly with atrial pacing in a similar manner in group A and group B (42 ± 19 ms at rest vs 53 ± 23 ms at 120 beats/min, P < 0.001 for group A, 39 ± 16 ms at rest vs 60 ± 19 ms at 120 beats/min, P < 0.001 for group B). Conclusions: We conclude that QT dispersion remains unchanged during atrial pacing at heart rates up to 120 beats/min in both individuals without structural heart disease and in patients with a history of sustained ventricular tachycardia. Correction by Bazett's formula results in prolongation of QTc dispersion, yielding values which may be misleading. A.N.E. 2002;7(1):47–52     

First Report of Tirofiban-Induced Anemia (Found in Combination with Severe Thrombocytopenia)

We describe the case of a 58-year-old man who developed acute severe anemia and thrombocytopenia after the administration of tirofiban following coronary artery angioplasty. The intravenous administration of IgG immunoglobulin completely resolved both the anemia and the thrombocytopenia. Although thrombocytopenia has been reported as a sequela to the use of tirofiban, there has been no prior report of a link between tirofiban use and anemia. Our successful resolution of both the anemia and the thrombocytopenia with immunoglobulin supports the theory that these severe sequelae of tirofiban are of autoimmune origin.Key words: Anemia, platelet aggregation inhibitors, platelet glycoprotein GPIIb/IIIa complex/drug effects, thrombocytopenia, tirofibanGlycoprotein IIb/IIIa receptor antagonists have been routinely used in the treatment of acute coronary syndromes and after percutaneous coronary interventions.¹ These drugs induce thrombocytopenia in approximately 2% to 5% of patients.² Thrombocytopenia is rapid in onset and is thought to be antibody mediated. Abciximab has been associated with a higher incidence of thrombocytopenia than has eptifibatide or tirofiban.^3–5 Severe thrombocytopenia (platelet count, <50 × 10³/μL) has occurred in 0.2% to 0.5% of patients in clinical trials.⁶ Here, we report a case of combined acute thrombocytopenia and anemia after tirofiban treatment in a patient who underwent elective percutaneous coronary angioplasty.