Evaluation of acute cardiovascular effects of immediate-release methylphenidate in children and adolescents with attention-deficit hyperactivity disorder

Attention-deficit hyperactivity disorder is a frequent condition in children and often extends into adulthood. Use of immediate-release methylphenidate (MPH) has raised concerns about potential cardiovascular adverse effects within a few hours after administration. This study was carried out to investigate acute effects of MPH on electrocardiogram (ECG) in a pediatric population. A total of 54 consecutive patients with attention-deficit hyperactivity disorder (51 males and 3 females; mean age =12.14±2.6 years, range 6–19 years), receiving a new prescription of MPH, underwent a standard ECG 2 hours before and after the administration of MPH 10 mg per os. Basal and posttreatment ECG parameters, including mean QT (QT interval when corrected for heart rate [QTc]), QTc dispersion (QTd) interval duration, T-peak to T-end (TpTe) intervals, and TpTe/QT ratio were compared. Significant modifications of both QTc and QTd values were not found after drug administration. QTd fluctuated slightly from 25.7±9.3 milliseconds to 25.1±8.4 milliseconds; QTc varied from 407.6±12.4 milliseconds to 409.8±12.7 milliseconds. A significant variation in blood pressure (systolic blood pressure 105.4±10.3 vs 109.6±11.5; P<0.05; diastolic blood pressure 59.2±7.1 vs 63.1±7.9; P<0.05) was observed, but all the data were within normal range. Heart rate moved from 80.5±15.5 bpm to 87.7±18.8 bpm. No change in TpTe values was found, but a statistically significant increase in TpTe/QTc intervals was found with respect to basal values (0.207±0.02 milliseconds vs 0.214±0.02 milliseconds; P<0.01). The findings of this study show no significant changes in ECG parameters. TpTe values can be an additional parameter to evaluate borderline cases

Potential clinical role of telomere length in human glioblastoma

Glioblastoma Multiforme (GBM) is the most common and lethal of human primary central nervous system (CNS) tumors. Due to the tumour’s intrinsic clinical and molecular heterogeneity, choice of initial treatment, prediction of survival, stratification of patients, prediction and monitoring of response to therapy, represent some of the greatest challenges in the management of GBM patients. Patients, despite optimal surgery, radiation and chemotherapy, still have a median survival of 14-16 months. A reason for this dismal prognosis is because of the relative inaccuracy of current prognostic markers, so far based on clinical or pathological variables. Molecular markers that effectively predict response to therapy and survival outcomes are limited. Consequently, there is a strong need to develop novel and independent markers of prognosis. Ideal biomarkers for solid tumors would serve one or more important functions. Telomeres, guanine-rich tandem DNA repeats of the chromosomal end, provide chromosomal stability, regulates important cellular processes, and seem to be implicated in human carcinogenesis. Recently, telomeres have been shown either to be associated with clinical markers of disease progression or to be independent markers of cancer prognosis in solid tumours, including GBM. Nevertheless, a corresponding comprehensive discussion of these promising developments in brain tumours has not yet been available in the literature. Therefore, here we reviewed studies focused on the assessment of telomeric length in brain tumours with the aim to emphasized those findings indicating a potential clinical role of telomeres in GBM. With the aim to enhance the awareness of the potential clinical role of telomeres’ length information in GBM, using a southern blot analysis, telomeric length in excised tumour samples was analyzed. Moreover, an attempt to correlated telomere length with patients’ overall survival, was also performed. The findings here reviewed shows some contradictory results, due to different tissues used as controls, but mainly to cellular and molecular heterogeneity in GBMs that drive molecular mechanisms controlling telomere length, included telomerase and Alternative Lengthening of Telomeres (ALT), through multiple mechanisms. However, overall these studies, including our own, are consistent with the hypothesis that GBMs’ telomeres were always shorter when compared with Normal Brain Tissue (NBT), and together with higher telomerase activity seem to be associated with malignancy and poor outcome; while tumours with ALT phenotype have longer telomeres, “less malignant” behaviour and better prognosis. We conclude that, although not entirely consistent in the type of telomere alteration, i.e., attrition vs. elongation, and unclear on the underlying mechanisms, multiple studies in brain tumours have shown that Translational Medicine @ UniSa, - ISSN 2239-9747 2011, 1(1): 243-270 245 Università degli Studi di Salerno telomere dysfunctions are associated with parameters of clinical outcome in patients with GBMs and therefore will be part of novel risk assessment and prognostic modalities for patients with these still dismal disease

[Disease activity assessment in large vessel vasculitis]

Disease activity assessment in large vessel vasculitis (LVV) is often challenging for physicians. In this study, we compared the assessment of disease activity based on inflammatory markers, clinical indices (Indian Takayasu Activity Score [ITAS] and the Kerr/National Institute of Health indices [Kerr/NIH]), and 18F-Fluorodesossiglucose (FGD) vascular uptake at positron emission tomography (Pet). We found that Pet results did not statistically correlate with the clinical indices ITAS and Kerr/NIH, because FDG uptake was increased (grade>2 on a 0-3 scale in at least one evaluated vascular segment) in many patients with inactive disease according to clinical and laboratory parameters (i.e., negative ITAS and Kerr/NIH indices as well as normal erythrocyte sedimentation rate (ESR) and C-reactive protein (PCR)). Similarly, interleukin- 6 and its soluble receptor did not statistically correlate with disease activity. In contrast, clinical indices showed a significant correlation between each other and with inflammatory markers (VES and PCR). These data suggest that while clinical indices and inflammatory markers may be useful to assess disease activity, Pet may be more sensitive

Consensus statement from the international consensus meeting on post-traumatic cranioplasty

Abstract: Background: Due to the lack of high-quality evidence which has hindered the development of evidence-based guidelines, there is a need to provide general guidance on cranioplasty (CP) following traumatic brain injury (TBI), as well as identify areas of ongoing uncertainty via a consensus-based approach. Methods: The international consensus meeting on post-traumatic CP was held during the International Conference on Recent Advances in Neurotraumatology (ICRAN), in Naples, Italy, in June 2018. This meeting was endorsed by the Neurotrauma Committee of the World Federation of Neurosurgical Societies (WFNS), the NIHR Global Health Research Group on Neurotrauma, and several other neurotrauma organizations. Discussions and voting were organized around 5 pre-specified themes: (1) indications and technique, (2) materials, (3) timing, (4) hydrocephalus, and (5) paediatric CP. Results: The participants discussed published evidence on each topic and proposed consensus statements, which were subject to ratification using anonymous real-time voting. Statements required an agreement threshold of more than 70% for inclusion in the final recommendations. Conclusions: This document is the first set of practical consensus-based clinical recommendations on post-traumatic CP, focusing on timing, materials, complications, and surgical procedures. Future research directions are also presented