Deregulated Chromatin Remodeling in the Pathobiology of Brain Tumors

Brain tumors encompass a heterogeneous group of malignant tumors with variable histopathology, aggressiveness, clinical outcome and prognosis. Current gene expression profiling studies indicate interplay of genetic and epigenetic alterations in their pathobiology. A central molecular event underlying epigenetics is the alteration of chromatin structure by post-translational modifications of DNA and histones as well as nucleosome repositioning. Dynamic remodeling of the fundamental nucleosomal structure of chromatin or covalent histone marks located in core histones regulate main cellular processes including DNA methylation, replication, DNA-damage repair as well as gene expression. Deregulation of these processes has been linked to tumor suppressor gene silencing, cancer initiation and progression. The reversible nature of deregulated chromatin structure by DNA methylation and histone deacetylation inhibitors, leading to re-expression of tumor suppressor genes, makes chromatin-remodeling pathways as promising therapeutic targets. In fact, a considerable number of these inhibitors are being tested today either alone or in combination with other agents or conventional treatments in the management of brain tumors with considerable success. In this review, we focus on the mechanisms underpinning deregulated chromatin remodeling in brain tumors, discuss their potential clinical implications and highlight the advances toward new therapeutic strategies.     

Adverse drug and device reactions in the oral cavity: Surveillance and reporting

BackgroundAccording to the U.S. Centers for Disease Control and Prevention, 48 percent of Americans (roughly 144 million people) used at least one prescribed medication in the preceding month; 11 percent used five or more. The authors describe the U.S. Food and Drug Administration's (FDA's) MedWatch program, the safety surveillance system for drugs and devices in the United States, and the dentist's role with regard to voluntary reporting of adverse effects (AEs). They also identify the most frequent AEs in the oral cavity as reported in the FDA Adverse Event Reporting System (FAERS).MethodsThe authors reviewed the literature regarding MedWatch, and they mined data in the FAERS public database for the 100 most commonly prescribed medications and their associated AEs.ResultsPharyngitis was the most common AE. Cough, dysgeusia and dysphagia also were common.ConclusionThe MedWatch program and its related databases contain useful information about AEs of pharmaceuticals and devices manifested in the oral cavity. Increased participation in the reporting of suspected adverse reactions will improve the national surveillance system and ultimately will protect patients' safety.Practical ImplicationsAs pharmaceutical consumption increases exponentially for a growing segment of the population, and as innovation in dental technology and devices flourishes, dentists have a distinct role in safeguarding patients' well-being. Promptly reporting AEs in the oral cavity improves quality of care and protects patients' well-being.     

Estimated low risk of rupture of small-sized unruptured intracranial aneurysms (UIAs) in relation to intracranial aneurysms in patients with subarachnoid haemorrhage

Objective

International guidelines for the management of unruptured intracranial aneurysms (UIAs) recommend observation in aneurysms <10 mm due to the estimated low risk of rupture. The aim of our study was analyse the data of recently treated patients with ruptured cerebral aneurysms with the special focus on size and configuration in view of the frequency scale in a daily routine setting.

Methods

We reviewed the data of all patients with aneurysmal subarachnoid haemorrhage (SAH) during the last 24 months at our institution. Configuration and size of the aneurysms were measured. Clinical data were collected using the following classifications for analysis: Hunt and Hess (H&H), modified Rankin Scale (mRS) and Fisher classification.

Results

Data of 135 patients with aneurysmal SAH (98 women, 37 men; ratio 2.6:1) were analysed. Analysis showed that 19 aneurysms (14 %) were >10 mm (mean size, 19.2 mm) and 116 aneurysms (85.9 %) <10 mm (mean size, 6.2 mm). In total, 112 were categorised as berry-like configured aneurysms (n?=?113 <10 mm, n?=?3 >10 mm), 18 as multi-lobar (n?=?16 <10 mm, n?=?2 >10 mm) and 5 as fusiform (n?=?4 <10 mm, n?=?1, >10 mm).

Conclusion

Since the results of our study showed that the majority of the aneurysms are <10 mm (mean, 6.2 mm), it is justified to challenge the recommendations of the international guidelines in a daily routine setting. We believe that the published data are not convincing enough to play a guidance role in daily routine. Due to improving surgical and endovascular techniques with satisfying results and the high number of ruptured small aneurysms, we believe a change in attitude in management of small-sized aneurysms is needed. Further diagnostic models are needed to determine the risk of rupture of intracranial aneurysms properly to obtain adequate treatment for UIAs.     

Successful surgical treatment of refractory amiodarone-induced thyrotoxicosis causing tachycardiomyopathy

Amiodarone is a well-established pharmacologic therapy used for several types of tachyarrhythmia. However, it is associated with potential adverse effects on thyroid function due to its high iodine concentration. Amiodaroneinduced thyrotoxicosis (AIT) is considered a difficult diagnostic problem that requires careful therapeutic strategy in order to balance the cardiologic and endocrine dysfunction associated with this condition. Herein, we report the case of a 52-year-old male patient who suffered from tachyarrhythmia due to paroxysmal atrial fibrillation. The patient had experienced recurring episodes of atrial fibrillation despite medical therapy with propafenone, sotalol and pulmonary vein isolation with catheter ablation. Amiodarone was subsequently administered, and temporary control of the arrhythmia was achieved. Six months after amiodarone treatment, the patient presented with uncontrollable tachycardia leading to heart failure, a condition known as tachycardiomyopathy. The thyroid function was assessed, and amiodarone-induced thyrotoxicosis was diagnosed. Unfortunately, AIT was refractory to treatment with carbimazole and cortisone and a surgical approach was decided. The patient eventually underwent a total thyroidectomy with complete control of the underlying arrhythmia, without the necessity for β-blockers. Heart failure was reversed and the patient has resumed his normal daily activities.     

Current concepts and controversies on adolescent idiopathic scoliosis: Part II

A new era in the surgical treatment of adolescent idiopathic scoliosis (AIS) opened with the introduction of pedicle screw instrumentation, which provides 3-column vertebral fixation and allows major deformity correction on the coronal, sagittal, and axial planes. A steep learning curve can be expected for spinal surgeons to become familiar with pedicle screw placement and correction techniques. Potential complications including injury to adjacent neural, vascular, and visceral structures can occur due to screw misplacement or pull-out during correction maneuvers. These major complications are better recognized as pedicle screw techniques become more popular and may result in serious morbidity and mortality. Extensive laboratory and clinical training is mandatory before pedicle screw techniques in scoliosis surgery are put to practice. Wider application, especially in developing countries, is limited by the high cost of implants. Refined correction techniques are currently developed and these utilize a lesser number of pedicle anchors which are strategically positioned to allow optimum deformity correction while reducing the neurological risk, surgical time, and blood loss, as well as instrumentation cost. Such techniques can be particularly attractive at a time when cost has major implications on provision of health care as they can make scoliosis treatment available to a wider population of patients. Pedicle screw techniques are currently considered the gold standard for scoliosis correction due to their documented superior biomechanical properties and ability to produce improved clinical outcomes as reflected by health-related quality-of-life questionnaires. Ongoing research promises further advances with the future of AIS treatment incorporating genetic counseling and possibly fusionless techniques.     

A national registry of haemoglobinopathies in Greece: deducted demographics, trends in mortality and affected births

Haemoglobinopathies are the most common hereditary disorders in Greece. Although there is a successful national prevention program, established 35 years ago, there is lack of an official registry and collection of epidemiological data for haemoglobinopathies. This paper reports the results of the first National Registry for Haemoglobinopathies in Greece (NRHG), recently organized by the Greek Society of Haematology. NRHG records all patients affected by thalassaemia major (TM), thalassaemia intermedia (TI), "H" Haemoglobinopathy (HH) and sickle cell disease (SCD). Moreover, data about the annual rate of new affected births along with deaths, between 2000 and 2010, are reported. A total of 4,506 patients are registered all over the country while the number of affected newborns was significantly decreased during the last 3 years. Main causes for still having affected births are: (1) lack of medical care due to financial reasons or low educational level; (2) unawareness of time limitations for prenatal diagnosis (PD); due either to obstetricians' malpractice or to delayed demand of medical care of couples at risk; and (3) religious, social or bioethical reasons. Cardiac and liver disorders consist main causes for deaths while life expectancy of patients lengthened after 2005 (p < 0.01). The NRHG of patients affected by haemoglobinopathies in Greece provides useful data about the haemoglobinopathies in the Greek population and confirms the efficacy of the National Thalassaemia Prevention Program on impressively decreasing the incidence of TM and sickle cell syndromes.     

Pathophysiology and pathogenesis of post-resuscitation myocardial stunning

The prognosis for cardiac arrest victims remains dismal, as only 17% survives to hospital discharge. Post-resuscitation myocardial stunning is the mechanical dysfunction that persists after the restoration of spontaneous circulation. Our knowledge regarding myocardial stunning has grown dramatically over the years, and several hypotheses have been proposed in order to explain its pathophysiology; however, the interrelationships among various mechanisms remain unclear. This review deals primarily with the basic aspects of the pathophysiology of post-resuscitation myocardial stunning. Given the large number of relevant studies and the fragmented information, an effort was made to summarize current knowledge in order to present a comprehensive pathophysiological mechanism. In this review, the pathophysiological disturbances occurring from the onset of cardiac arrest until the restoration of spontaneous circulation are addressed. Then, the pathophysiology of myocardial stunning during the post-resuscitation period is critically reviewed in 4 parts, the immediate, the early, the intermediate, and the recovery post-arrest phase. This article covers a huge gap in the existing literature regarding the pathophysiology of post-resuscitation period and provides a better understanding of the pathophysiology and pathogenesis of post-resuscitation myocardial stunning.