Deferasirox effectively reduces iron overload in non-transfusion-dependent thalassemia (NTDT) patients: 1-year extension results from the THALASSA study

Patients with non-transfusion-dependent thalassemia (NTDT) often develop iron overload that requires chelation to levels below the threshold associated with complications. This can take several years in patients with high iron burden, highlighting the value of long-term chelation data. Here, we report the 1-year extension of the THALASSA trial assessing deferasirox in NTDT; patients continued with deferasirox or crossed from placebo to deferasirox. Of 133 patients entering extension, 130 completed. Liver iron concentration (LIC) continued to decrease with deferasirox over 2 years; mean change was ?7.14 mg Fe/g dry weight (dw) (mean dose 9.8?±?3.6 mg/kg/day). In patients originally randomized to placebo, whose LIC had increased by the end of the core study, LIC decreased in the extension with deferasirox with a mean change of ?6.66 mg Fe/g dw (baseline to month 24; mean dose in extension 13.7?±?4.6 mg/kg/day). Of 166 patients enrolled, 64 (38.6 %) and 24 (14.5 %) patients achieved LIC <5 and <3 mg Fe/g dw by the end of the study, respectively. Mean LIC reduction was greatest in patients with the highest pretreatment LIC. Deferasirox progressively decreases iron overload over 2 years in NTDT patients with both low and high LIC. Safety profile of deferasirox over 2 years was consistent with that in the core study.     

Physical activity is associated with bone geometry of premenarcheal girls in a dose-dependent manner

ObjectiveTo determine the relationship between habitual physical activity (PA) level and peripheral qualitative computed tomography-determined quantitative tibia characteristics of premenarcheal girls.MethodsPremenarcheal girls matched for age (10–13 years), bone age and maturity level were assigned into: a) low PA group (LPA, n = 25), b) moderate PA group (MPA, n = 17), and c) high PA group (HPA, n = 18). Participants’ daily dietary intake, tibia’s geometry and serum levels of calcium and vitamin D were assessed.ResultsPremenarcheal girls demonstrating HPA exhibited greater pericortical thickness, cross-sectional area (CSA) and bone mineral content (BMC) (p < .001) in cortical bone, greater BMC, volumetric bone density (vBMD) and polar stress strength index (SSIp) in trabecular bone (p < 0.001–0.05) and greater total BMC (p < .05) and vBMD (p < .01) when compared to their physically inactive or moderately active counterparts. MPA exhibited greater values of cortical BMC (p < .01) and SSIp (p < .05) than LPA. Partial correlation analysis (adjusted for BMI) revealed modest associations between PA score and bone geometry parameters (r = 0.36–0.49, p < .05) at 38% of tibia length.ConclusionsHabitual PA affects geometry of both cortical and trabecular areas of a long bone of premenarcheal girls in a dose-dependent manner. Specifically, PA increases both the density and size of cortical bone but only the density of trabecular bone during preadolescence. Given the importance of peak bone mass for future fracture risk, high levels of PA during childhood could be a major target for public health interventions aimed at optimising bone health in prepubertal children when the greatest bone gains occur.     

Total arterial compliance,estimated by a novel method,is better related to left ventricular mass compared to aortic pulse wave velocity: The SAFAR study

Aim: The investigation of the association between total arterial compliance (C_T)—estimated by a novel technique—with left ventricular mass (LVM) and hypertrophy (LVH). Our hypothesis was that C_T may be better related to LVM compared to the gold-standard regional aortic stiffness. Within the frame of the ongoing cross-sectional study “SAFAR,” 226 subjects with established hypertension or with suspected hypertension underwent blood pressure (BP) assessment, carotid-to-femoral pulse wave velocity (cf-PWV), and echocardiographic measurement of LVM. LVM index (LVMI) was calculated by the ratio of LVM to body surface area. C_T was estimated by a previously proposed and validated formula: C_T = 36.7 /cf-PWV² [ml/mmHg]. LVMI was related to age (r = 0.207, p = 0.002), systolic BP (r = 0.248, p < 0.001), diastolic BP (r = 0.139, p = 0.04), mean BP (r = 0.212, p = 0.002), pulse pressure (r = 0.212, p = 0.002), heart rate (r = ?0.172, p = 0.011), cf-PWV (r = 0.268, p < 0.001), and C_T (r = ?0.317, p < 0.001). The highest correlation was observed for C_T that was significantly stronger than the respective correlation of cf-PWV (p < 0.001). In multivariate analysis, C_T was a stronger determinant, compared to cf-PWV, of LVMI and LVH. It remains to be further explored whether C_T has also a superior prognostic value beyond and above local or regional (segmental) estimates of pulse wave velocity.     

Cortical interactions during the experience of auditory verbal hallucinations

Auditory verbal hallucinations (AVHs), the perception of voices in the absence of auditory stimuli, are common and distressing symptoms reported by 50%-80% of patients with schizophrenia. However, the results in a number of imaging and electrophysiological studies on the origins of AVH are not consistent, and the underlying pathophysiology remains unclear. The authors enrolled a group of schizophrenia patients and normal-control subjects, age 18-45 years. Two patient groups participated in the study; 1) a group of 8 patients with drug-resistant spontaneous AVHs; and 2) a group of 7 patients whose AVHs were successfully controlled with neuroleptic medication; along with 16 normal-control subjects. The entire sample had EEG recording done, with the AVH group told to press a button when they experienced a hallucination, and the other two groups randomly told when to press the button. In the AVH group, hallucinations were longer in the "eyes-closed" than "eyes-open" condition. There was spreading phase-coupling in the AVH group, intra- and inter-hemispherically, at left and right frontal and temporal areas, under both eyes-closed and eyes-open condition, during the experience of AVH. There was a statistically significant increase of α-band frequency-specific synchrony maximum values in the AVH group. AVHs are considered to be complex features, and, as such, they reflect abnormal functional connectivity in multiple related regions in both intra- and inter-hemispherical brain sites, primarily defined by phase-integration.