Hematologic responses to deferasirox therapy in transfusion-dependent patients with myelodysplastic syndromes

Background

Reductions in transfusion requirements/improvements in hematologic parameters have been associated with iron chelation therapy in transfusion-dependent patients, including those with myelodysplastic syndromes; data on there reductions/improvements have been limited to case reports and small studies.

Design and Methods

To explore this observation in a large population of patients, we report a post-hoc analysis evaluating hematologic response to deferasirox in a cohort of iron-overloaded patients with myelodysplastic syndromes enrolled in the Evaluation of Patients’ Iron Chelation with Exjade^® (EPIC) study using International Working Group 2006 criteria.

Results

Two-hundred and forty-seven, 100 and 50 patients without concomitant medication for myelodysplastic syndromes were eligible for analysis of erythroid, platelet and neutrophil responses, respectively. Erythroid, platelet and neutrophil responses were observed in 21.5% (53/247), 13.0% (13/100) and 22.0% (11/50) of the patients after a median of 109, 169 and 226 days, respectively. Median serum ferritin reductions were greater in hematologic responders compared with non-responders at end of study, although these differences were not statistically significant. A reduction in labile plasma iron to less than 0.4 μmol/L was observed from week 12 onwards; this change did not differ between hematologic responders and non-responders.

Conclusions

This analysis suggests that deferasirox treatment for up to 1 year could lead to improvement in hematologic parameters in some patients with myelodysplastic syndromes.     

Safety in the Use of Dexmedetomidine (Precedex) for Deep Brain Stimulation Surgery: Our Experience in 23 Randomized Patients

Objective: Evaluation of safety and efficacy of dexmedetomidine in deep brain stimulation (DBS) surgery. Materials and Methods: A cohort of 23 patients, candidates for DBS for Parkinson's disease, Tourette syndrome, or obsessive‐compulsive disorder, was randomized in two groups: dexmedetomidine group and control group. Standard anesthesiologic parameters were recorded and analyzed, together with the need for other medications. A ten‐degree scale (visual analog scale) assessing patient discomfort during DBS also was recorded at the end of surgery. Results: The results demonstrated good stability of intraoperative monitoring: no respiratory depression and good overall cooperation with the neurologist, while no side‐effects were recorded. Conclusions: Our conclusion is that dexmedetomidine should be considered as a valuable option for sedation in poorly collaborating patients undergoing DBS surgery.     

Genetic variation in the neuropeptide y gene promoter is associated with increased risk of tobacco smoking

Background: Neuropeptide Y (NPY) is a strong candidate gene regarding the pathophysiology of tobacco dependence. It has been associated with various addictive and psychiatric disorders, and closely interacts with the brain reward system. The aim of the present study was to test for association between a functional genetic variant in the NP-Y promoter gene (SNP rs16147) and tobacco smoking. Methods: In a population-based case-control multicenter study designed for tobacco addiction research, a total of 550 Caucasian current smokers, and 544 never-smokers were genotyped for SNP rs16147 and behaviorally characterized with the State-Trait Anxiety Inventory (STAI). Results: Subjects with TT genotype of the SNP rs16147 were significantly more frequently smokers than never-smokers (p = 0.046). In addition, TT genotype exhibited increased state anxiety scores compared to carriers of the C allele (p = 0.037). Conclusions: Our results provide evidence for an involvement of the functionally relevant SNP rs16147 in the pathophysiology of tobacco dependence. Further studies are needed to confirm our findings.     

Combination or sequencing strategies to improve the outcome of metastatic renal cell carcinoma patients: a critical review

The introduction of novel anti-angiogenic therapies has greatly improved the outcome of patients with metastatic renal cell carcinoma (mRCC). The use of these therapies in combination or sequentially is proposed to provide greater efficacy. We have reviewed completed and ongoing clinical trials in mRCC that have reported efficacy and/or safety data of novel therapies used in combination or sequentially. Bevacizumab appears to be a useful partner when combined with interferon (IFN), while controversial results have been reported when combined with temsirolimus and everolimus. Other combinations appear to have unacceptable tolerability or require dose or schedule optimization. Sequencing data provide a clear indication that multiple lines of treatment may extend survival. The 'ideal' sequence, however, is still unknown. In conclusion, novel therapies used in combination or sequentially have potential to provide optimised treatment and patient outcomes in mRCC. The results from ongoing/planned trials are expected to help shape future therapy.     

The role of Doppler ultrasound in rheumatic diseases

The use of Doppler techniques, including power, colour and spectral Doppler, has greatly increased in rheumatology in recent years. This is due to the ability of Doppler US (DUS) to detect pathological vascularization within joints and periarticular soft tissues, thereby demonstrating the presence of active inflammation, which has been reported to be correlated with the local neo-angiogenesis. In synovitis, DUS showed a high correlation with histological and MRI findings, thus it is considered a valid tool to detect pathological synovial vascularization. Moreover, it is more sensitive than clinical examination in detecting active joint inflammation and in the evaluation of response to treatment. In addition, DUS may be considered as a reference imaging modality in the assessment of enthesitis, MRI being not sensitive and histology not feasible. Moreover, it has been demonstrated to be able to detect changes in asymptomatic enthesis. In conclusion, DUS is a useful and sensitive tool in the evaluation and monitoring of active inflammation. Its widespread use in clinical rheumatological practice is recommended. The aim of this article is to review the current literature about the role of DUS in rheumatic diseases, analysing its validity, reliability and feasibility.     

猪精子细胞中胰岛素诱导产生的一氧化氮自由基促进精子获能

近期,胰岛素被证实具有诱导猪精子获能的能力。在不同的哺乳动物中,精子获能被认为与一氧化氮信号通路相关;因此,本研究使用荧光激活细胞分选技术探究经胰岛素处理的猪精子中一氧化氮水平。在同一样本中,用金霉素染色、蛋白质酪氨酸磷酸化模式和顶体状态来评估精子获能。结果显示经胰岛素处理的精子内一氧化氮水平及三种评价精子获能的指标均有显著提高;相反,用一氧化氮合成酶抑制剂（N-硝基-L-精氨酸甲酯）或抗胰岛素受体β抗体预处理的精子中胰岛素相关的作用全被逆转。这些结果表明胰岛素具有增强猪精子细胞内一氧化氮浓聚的能力并且提示胰岛素可能通过一氧化氮促进精子获能。     

Pathological gambling in Parkinson's disease: Subthalamic oscillations during economics decisions

Pathological gambling develops in up to 8% of patients with Parkinson's disease. Although the pathophysiology of gambling remains unclear, several findings argue for a dysfunction in the basal ganglia circuits. To clarify the role of the subthalamic nucleus in pathological gambling, we studied its activity during economics decisions. We analyzed local field potentials recorded from deep brain stimulation electrodes in the subthalamic nucleus while parkinsonian patients with (n = 8) and without (n = 9) pathological gambling engaged in an economics decision‐making task comprising conflictual trials (involving possible risk‐taking) and non conflictual trials. In all parkinsonian patients, subthalamic low frequencies (2–12 Hz) increased during economics decisions. Whereas, in patients without gambling, low‐frequency oscillations exhibited a similar pattern during conflictual and non conflictual stimuli, in those with gambling, low‐frequency activity increased significantly more during conflictual than during non conflictual stimuli. The specific low‐frequency oscillatory pattern recorded in patients with Parkinson's disease who gamble could reflect a subthalamic dysfunction that makes their decisional threshold highly sensitive to risky options. When parkinsonian patients process stimuli related to an economics task, low‐frequency subthalamic activity increases. This task‐related change suggests that the cognitive‐affective system that drives economics decisional processes includes the subthalamic nucleus. The specific subthalamic neuronal activity during conflictual decisions in patients with pathological gambling supports the idea that the subthalamic nucleus is involved in behavioral strategies and in the pathophysiology of gambling. © 2013 International Parkinson and Movement Disorder Society