bluuebunny/crossref_metadata_2025 huggingface dataset:
Innovations in Headache Management - Recent Advances and Future Perspectives
Authors: Nagy Abraham J , Rapoport Alan M ,   Neurologist, Nevada Headache institute. Las Vegas, Nevada, US,   Clinical Professor of Neurology, David Geffen School of Medicine, University of California, Los Angeles, California, US
Published: October 2015

Since the advent of triptans over two decades ago, progress on new therapeutics for headache management has seemingly slowed as few new lines of care have become available. with major advances in the understanding of headache disorder neurobiology, new therapies are on the horizon. This article will review novel delivery systems of familiar medications and new lines of care with unique therapeutic targets. Promising new therapies like calcitonin gene-related peptide (CGRP) receptor antagonists and 5-hydroxytrypamine (5-HT) 1F receptor agonists are in late-stage development. One neurotoxin has recently been approved for the prevention of chronic migraine. Neuromodulation techniques have rapidly advanced over the last few years. Several new drug targets such as nitric oxide synthase, gap junction modulators, glutamate receptor antagonists, orexin antagonists, transient receptor potential vanilloid 1 (TRPV1) receptor modulators, prostanoid receptors antagonists and pituitary adenylate cyclase 1 (PAC1) receptor antagonists await development. The therapies in the coming decade show great promise for distinctly advancing headache management.
Update on Levodopa/Carbidopa Intestinal Gel Infusion
Authors: Nyholm Dag ,   Associate Professor, Department of Neuroscience, Neurology, Uppsala University, Uppsala, Sweden
Published: October 2015

Recent data on levodopa/carbidopa intestinal gel (LCIG) infusion are discussed in this article. LCIG infusion provides improvements in ‘off’ time and dyskinesia via continuous dopaminergic stimulation (CDS). In the long-term, LCIG infusion appears to maintain efficacy without the need to increase dosages. The growing number of publications on LCIG infusion shows the increasing experience and interest in this therapy. The new data demonstrate the effects of using LCIG infusion in combination with catechol-O-methyl transferase inhibitors, and technical improvements to the pump system (e.g., to the tubing). Despite the invasive nature of LCIG infusion, nearly all patients would recommend this treatment. Furthermore, a number of larger-scale studies on this particular CDS therapy are in progress.
Beyond Motor Symptoms – Impact of Continuous Dopaminergic Stimulation on Non-motor and Social Aspects of Advanced Parkinson’s Disease
Authors: Pickut Barbara ,   Neurologist, Department of Neurology, University Hospital Antwerp (UZA), Edegem, Belgium
Published: October 2015

Two patient cases are presented here that illustrate the benefits of continuous dopaminergic stimulation on the non-motor symptoms of Parkinson’s disease. In both cases, levodopa/carbidopa intestinal gel infusion therapy led to improvements in anxiety, depression, concentration, urge incontinence, sexual function, sleep, vivid dreams and rapid eye movement sleep behaviour disorder, pain, sweating and feelings of self-assuredness. Such improvements have an impact on patients’ quality of life and can help their social functioning.
Managing for the Long-term – Strategies for Initiating and Maintaining Successful Continuous Dopaminergic Stimulation Treatment
Authors: Henriksen Tove , Odin Per , Volkmann Jens , Antonini Angelo ,   Consultant, Movement Disorder Clinic, Bispebjerg Hospital, University Hospital of Copenhagen, Denmark,   Chairman, Department of Neurology, Klinikum-Bremerhaven, Bremerhaven, Germany and Professor, Department of Neurology, Lund University Hospital, Lund, Sweden,   Chairman, Department of Neurology, University Hospital Würzburg, Germany,   Director, Parkinson Unit, IRCCS San Camillo, Venice, and University of Padua, Padua, Italy
Published: October 2015

There are many factors that may influence treatment choice in patients with Parkinson’s disease. While ‘inclusion’ criteria include the clinical need for short- and long-term improvement, there are some well defined contraindications to continuous dopaminergic stimulation (CDS) therapies, such as age, cognitive impairment, psychosis or severe orthostatic hypotension. These contraindications vary between CDS therapies and can help guide the choice of treatment. Patient preferences and the practicalities of the treatment modality also play an important part in the decision-making process. Treatment selection algorithms have been developed and presented, but they require refining and need to be expanded to include guidance on management decisions – for example, when initial CDS therapy fails. While more trial data are gathered and as management algorithms evolve, case studies continue to provide important information on practical aspects of CDS therapies.
Two Decades of Evolving Care with Pump Therapies – What have we Learned?
Authors: Lees Andrew ,   Director, Reta Lila Weston Institute of Neurological Studies, Institute of Neurology, University College London, London, UK
Published: October 2015

Since the discovery that the gold standard treatment in Parkinson’s disease (PD), oral levodopa, contributes to motor fluctuations, the treatment strategy of delivering dopaminergic drugs in a continuous manner has been investigated. Motor fluctuations are believed to be the result of a combination of progressive denervation of the striatum with advancing disease and erratic gastric emptying with oral levodopa, which leads to peaks and troughs in plasma levodopa concentration and thus pulsatile stimulation of dopaminergic neurons. Methods have been developed to provide continuous dopaminergic stimulation, such as the delivery of apomorphine by subcutaneous infusion and levodopa/carbidopa by intestinal gel infusion. These therapies have been shown to significantly reduce ‘off’ time and improve motor fluctuations, and therefore have been a major advance in the management of PD.
Critical Features in the Development of Exercise-based Interventions for People with Huntington's Disease
Authors: Quinn Lori , Rosser Anne , Busse Monica ,   Senior Research Fellow, School of Healthcare Studies, Cardiff University, UK,   Professor of Clinical Neuroscience and Honorary Consultant Neurologist, University Hospital of Wales, Cardiff, UK; Co-director, Brain Repair Group, Cardiff University, UK,   Senior Lecturer, School of Healthcare Studies, Cardiff University, UK
Published: October 2015

Exercise and physical therapies are increasingly being considered as a lifestyle intervention in people with Huntington's disease (HD). In addition to possible effects on motor function, there may be benefits in mood, behaviour and cognition from early in the disease. Certainly exercise may also infer general health benefits and there are recent suggestions that exercise may indeed potentiate disease modification. This review provides an overview of a strategic approach to the development and evaluation of complex exercise interventions in this neurodegenerative disease with a view to informing future clinical trials.
Magnetic Resonance Imaging Techniques in the Evaluation of Stroke and Neurovascular Disease
Authors: Essig Marco , Tanenbaum Lawrence ,   Professor of Radiology, Department of Neuroradiology, University Hospital Erlangen, Germany,   Associate Professor of Radiology, Department of Radiology, Mount Sinai Hospital, New York, US
Published: October 2015

Early intervention remains vital in the management of acute stroke. The goals of imaging techniques are to establish a diagnosis as early as possible and to obtain accurate information about the intracranial vasculature and brain perfusion to guide therapeutic decisionmaking. Magnetic resonance imaging (MRI) and contrast-enhanced magnetic resonance angiography (CE-MRA) are valuable techniques in the evaluation of acute stroke and can provide diagnostic information on the underlying pathophysiological changes. Gadolinium-based contrast agents (GBCAs) facilitate the diagnosis of ischaemic stroke by accentuating abnormal flow kinetics and the diagnosis of nonischaemic stroke by assisting in the detection and characterisation of intracranial aneurysms and arteriovenous malformations (AVMs). Contrast agents may also be employed in the characterisation of vascular atherosclerotic plaque. Gadobutrol (Gadovist®, Gadavist®) is a high relaxivity contrast agent which combines an excellent safety profile and proven high efficacy. As the only high concentration contrast media it allows to inject at a small and compact bolus, which has a direct impact on the performance of MRA or perfusion MRI procedure.
Amyotrophic Lateral Sclerosis – Clinical Features, Pathophysiology and Management
Authors: Coupé Christophe , Gordon Paul H ,   Clinician Psychologist,   Visiting Neurologist and Researcher, Centre référent maladie rare SLA, Département des Maladies du Système Nerveux, Hôpital de la Pitié-Salpêtrière, Paris, France
Published: October 2015

Amyotrophic lateral sclerosis (ALS), first described by Jean-Martin Charcot 145 years ago, is an age-related neurodegenerative disorder that leads to destruction of motor neurons. The disease begins focally in the central nervous system then spreads inexorably. The clinical diagnosis, defined by progressive upper and lower motor neuron findings, is confirmed by electromyogram. Additional testing excludes other conditions. The disease is heterogeneous, but most patients die of progressive weakness and respiratory failure less than 3 years from symptom onset. Like other neurodegenerative diseases, ALS is thought to have genetic and environmental causes. Five to 10 % of cases are inherited. Genetic factors, age, tobacco use and athleticism may contribute to sporadic ALS, but major causes are unidentified for most patients. Complex pathophysiological processes, including mitochondrial dysfunction, aggregation of misfolded protein, oxidative stress, excitotoxicity, inflammation and apoptosis, involve both motor neurons and surrounding glial cells. There is clinical and pathological overlap with other neurodegenerative diseases, particularly frontotemporal dementia. One medication, riluzole, which was approved in 1996, prolongs survival by several months. Numerous ensuing clinical trials have been negative. Researchers currently aim to slow disease progression by targeting known pathophysiological pathways. Approaches under examination are directed at muscle protein, energetic balance, cell replacement and protein aggregation. Until the causes and more robust neuroprotective agents are identified, symptomatic therapies can help improve expectancy and quality of life. Palliative care ensures dignity in advanced stages.
Intra-operative Imaging for Brain Tumour Resection in Paediatric Patients
Authors: Parks Christopher , Avula Shivaram , Abernethy Laurence J , Wright Elizabeth J , Mallucci Conor L ,   Consultant Paediatric Neurosurgeon,   Consultant Paediatric Neuroradiologist,   Consultant Paediatric Neuroradiologist,   Consultant Paediatric Anaesthetist, Alder Hey Children’s NHS Foundation Trust, Liverpool, UK,   Consultant Paediatric Neurosurgeon
Published: October 2015

There is currently significant investment by healthcare providers into intra-operative magnetic resonance imaging (ioMRI). It is an expensive technology, but due to its proven benefit in tumour resection it is becoming the gold standard of care in brain tumour resection. Alder Hey Hospital has routinely used this technology since 2009. In our department, ioMRI has been used in approximately 130 cases. These consist predominantly of resective tumour cases but also include biopsies, epilepsy surgery and other complex cases. In tumour resections 32 % had further resection following ioMRI under the same anaesthetic. Unnecessary early return to theatre has been reduced from 14 % prior to the use of ioMRI to 0 % within 6 months of surgery. The adoption of this technology as an adjunct to paediatric neurosurgery has led to a significant improvement in the service delivered. It is possible that the application of advanced MRI techniques will improve this even further.
Clinical, Biochemical and Imaging Parameters that may be Predictive of High Disease Activity, Rapid Progression or Increased Disability in Multiple Sclerosis
Authors: Svenningsson Anders , Hendin Barry A ,   Associate Professor of Neurology, Department of Neurology, Umeå University Hospital, Umeå, Sweden,   Clinical Professor of Neurology, University of Arizona Medical School, Phoenix, Arizona, US
Published: October 2015

Increased ability to predict disease course and response to disease-modifying therapies in multiple sclerosis (MS) would optimise treatment outcomes by guiding selection of patients for a particular therapeutic intervention. Several factors affecting disease progression have been identified, including individual characteristics such as age at onset and race onset of symptoms, early disease outcomes and radiological measures. While studies of magnetic resonance imaging (MRI) prognostic indicators have given mixed results, advances in technology are increasing the predictive power of MRI, and new techniques and outcome measures are providing alternative means of predicting disease course and response to treatment. The search for a predictive biomarker is an area of active research but studies remain poorly validated. Potential biomarkers include neurofilament proteins, microRNAs, gene expression and antibodies. Since it is unlikely that a single factor may predict disease course, a number of composite scoring systems have been proposed, but none have yet received widespread acceptance. However, it seems likely that in the future, a combination of MRI and biochemical biomarkers will provide a foundation for therapeutic decision-marking in MS allowing an individualised approach.
Hidden Disabilities in Multiple Sclerosis  The impact of Multiple Sclerosis on Patients and their Caregivers
Authors: Giovannoni Gavin , Fole John F , Brandes David W ,   Professor of Neurology, Queen Mary University of London, Blizard institute, Barts and The London School of Medicine and Dentistry, London, UK,   Neurologist and Director, Rocky Mountain Multiple Sclerosis Clinic, Salt Lake City, Utah, US,   Neurologist, Hope Neurology, Knoxville, Tennessee, US
Published: October 2015

Multiple sclerosis (MS) is a heterogeneous condition that presents with a large variety of symptoms. While motor functions including coordination, gait and walking ability are clearly visible to clinicians, including MS specialists. These are sometimes termed hidden disabilities and are often overlooked because patients do not mention them in consultations, either because they are embarrassed, do not want to disappoint their family and therefore do not mention the symptoms, or they have not linked the symptoms to their disease. Hidden disabilities in MS include cognition and memory impairment, depression, anxiety and pseudobulbar affect, pain, fatigue, sleep disorders, bowel, bladder and sexual dysfunctions, osteopenia and osteoporosis. These disabilities are associated with a reduced quality of life in patients, their families and caregivers, and affect the ability of patients to function in everyday life. Pharmacological treatments and other interventions are available to manage these symptoms; however, the effectiveness of these interventions in MS is variable. There is need for greater recognition and further research into therapeutic options to reduce the burden of hidden disabilities in MS.
Breakthrough Disease in Multiple Sclerosis  The Problem and Treatment Options
Authors: Fox Edward J , Havrdova Eva ,   Clinical Assistant Professor, University of Texas Medical Branch, MS Clinic of Central Texas, Central Texas Neurology Consultants, Round Rock, Texas, US,   Head, MS Centre and Professor, Department of Neurology, First medical Faculty, Charles University in Prague, Prague, Czech Republic
Published: October 2015

Early intervention with a disease-modifying therapy (DMT) is the most effective strategy for achieving disease control of relapsingremitting multiple sclerosis (RRMS). However, current DMTs for RRMS are only partially effective in reducing disease activity, and approximately two-thirds of patients experience breakthrough disease. Breakthrough disease is characterised as an unacceptable degree of clinical or imaging evidence of disease activity, or progression, despite treatment. No validated definition of what constitutes unacceptable disease activity, or progression, despite treatment. No validated definition of what constitutes unacceptable disease activity currently exists and identification of the condition remains challenging. Given the heterogeneous nature of MS, standard protocols will not be applicable to everyone. Managment of breakthrough disease should be tailored to the individual, involving close monitoring of both clinical and magnetic resonance imaging parameters. Treatment options include increasing the dose, switching to another first-line therapy, escalation to a second-line therapy and the addition of other agents as combination therapy. There is a lack of evidence-based data to justify such approaches, but given the limited window of opportunity to derive the maximum benefit from DMTs, treatment modification where indicated is crucial. Various algorithms for the identification and treatment of breakthrough disease are discussed, and new and emerging therapies reviewed.
Effect of Therapeutic Interventions on Health-related Quality of Life in Parkinson’s Disease
Authors: Reichmann Heinz , Martin Pablo Martínez , Stocchi Fabrizio ,   Professor of Neurology and Chairman, Department of Neurology, University of Dresden Medical School, Dresden, Germany,   Neurologist, Tenured Scientist of the Public Boards of Research, and Head of the Neuroepidemiology Section, National Centre of Epidemiology and CIBERNED, Carlos III Institute of Health, Madrid, Spain,   Professor of Neurology and Director, Parkinson’s Disease and Movement Disorders Research Centre, Institute for Research and Medical Care, IRCCS San Raffaele, Rome, Italy
Published: October 2015

Health-related quality of life (HRQoL) used to be considered a secondary parameter in clinical trials of Parkinson’s disease (PD) and in routine clinical practice, but is now increasingly recognised as an important measure of patient status. A number of studies have shown that the severity of PD is strongly associated with poor HRQoL scores and that measuring HRQoL domains provides a valuable assessment of overall patient status. Current guidelines from the Movement Disorder Society Task Force and the European Parkinson’s Disease Association recommend the use of HRQoL measures in the diagnosis and monitoring of patients. The European Medicines Agency PD Guidelines, however, do not yet recommend the use of such indirect endpoints in clinical trials. A series of phase III and post-marketing studies evaluating the selective monoamine oxidase type B inhibitor, rasagiline in PD, including between 404 and 1,176 patients, showed that treatment with rasagiline leads to significant improvements in HRQoL parameters such as the Parkinson’s Disease Quality of Life questionnaire (PDQUALIF), the 39-Item Parkinson’s Disease Questionnaire (PDQ-39), the PDQ-8 and other HRQoL-related parameters. Other clinical trials have shown significant improvements in parameters including: Short-Form-36, EuroQuol 5D, PDQUALIF, PDQ-39 and HRQoL-related parameters in PD patients treated with dopamine agonists, selegiline, tocopherol or levodopa/carbidopa/entacapone or levodopa/carbidopa combinations. Experience gained with these instruments is likely to increase the attention paid to HRQoL in PD assessment and could improve diagnosis and monitoring of PD and may ultimately improve patient outcomes.
Emerging Role of Safinamide in Parkinson’s Disease Therapy
Authors: Kulisevsky Jaime ,   Movement Disorders Unit, Neurology Department, Sant Pau Hospital, Autonomous University of Barcelona, Barcelona, Spain; Estudis de Ciències de la Salut, Universitat Oberta de Catalunya (UOC), Barcelona, Spain; CIBERNED, Instituto de Salud Carlos III, Madrid, Spain
Published: October 2015

Parkinson’s disease is associated with motor complications, especially dyskinesias, which limit dopaminergic replacement therapy. Safinamide is a water-soluble, orally active a-aminoamide derivative that modulates dopaminergic and glutamatergic neurotransmission with a unique dual mechanism of action. It improves motor symptoms, motor complications, quality of life and ‘on’ and ‘off’ time even in combination with other Parkinson’s disease (PD) medications, such as dopamine agonists and levodopa (LD). Safinamide reduces ‘off’ time and extends ‘on’ time without troublesome dyskinesia. Furthermore, safinamide maintains its effects after long-term treatment and has a favourable pharmacokinetic and side-effect profile. It therefore has the potential to become an important drug in PD management. This review will summarise data from animals, healthy human subjects and patients with PD on the long-term efficacy and safety of safinamide.
Advances in Atrial Fibrillation-related Stroke Prevention
Authors: Amarenco Pierre , Hacke Werner , Norrving Bo , Rost Natalia ,   Professor and Chairman, Department of Neurology and Stroke Centre, Bichat Hospital, Paris, France,   Professor and Chairman, Department of Neurology, University of Heidelberg, Germany,   Professor, Department of Clinical Neuroscience, Lund University Hospital, Lund, Sweden,   Director, Acute Stroke Services, Massachusetts General Hospital and Associate Professor of Neurology, Harvard Medical School, Massachusetts, US
Published: October 2015

In patients with atrial fibrillation (AF) the risk of stroke is substantially increased, especially in those who are elderly (over 75 years) or have risk factors such as previous stroke, heart failure or hypertension. Stroke outcomes are also generally much worse in those with AF. Current guidelines indicate that any patient with AF and risk factors for stroke should receive anticoagulant therapy to limit their stroke risk. Despite these established recommendations, only 50 % of patients at risk receive anticoagulation with a vitamin K antagonist (VKA) and only 50 % of those are within the therapeutic range, indicating lack of adherence to the guidelines. Withholding anticoagulant therapy is mainly left to an individual physician’s choice, as shown in the ongoing GARFIELD registry of AF stroke prevention practice. Many physicians fear the risk of intracranial haemorrhage (ICH) for which outcomes remain poor. Recent clinical studies have shown that the non-VKA oral anticoagulants (NOACs) (apixaban, rivaroxaban, dabigatran and edoxaban) significantly reduce the risk of ICH and other bleeding events, while having non-inferior stroke prevention to warfarin. Use of these drugs, limiting exposure to aspirin and alcohol and controlling blood pressure have been shown to minimise ICH risk in large clinical trials and meta-analyses. Recent data from the Effective aNticoaGulation with factor xA next GEneration in Atrial Fibrillation (ENGAGE AF)-TIMI 48 study showed that the factor Xa inhibitor edoxaban was non-inferior to well-managed warfarin for reducing all stroke risk, and significantly reduced haemorrhagic stroke, major bleeding, ICH and death. These findings further support the case for using NOAC therapy for stroke prevention in patients with AF and risk factors for stroke.
Breaking the Barriers  A European Employment Pact for Multiple Sclerosis
Authors: Rogan Emma , Kasilingam Elisabeth , Berbece Claudiu ,   EMSP Project Coordinator,   EMSP Programme Manager,   EMSP Communications Coordinator, EMSP aisbl, European Multiple Sclerosis Platform, Brussels, Belgium
Published: October 2015

In March this year, the European Multiple Sclerosis Platform (EMSP) launched its European Employment Pact for people with multiple sclerosis (MS) and other neurodegenerative conditions. A call to action for the Pact will follow in May. EMSP is inviting all relevant stakeholders, from businesses to decision-makers, to pledge support. People who are highly educated and skilled are edged out of the workplace by inadequate ‘return to work’ policies, lack of understanding and prejudice. EMSP considers this unacceptable.
Hunter Syndrome (Mucopolysaccharidosis II) – The Signs and Symptoms a Neurologist Needs to Know
Authors: Amartino Hernan ,   Head of Child Neurology Department, Hospital Universitario Austral, Buenos Aires, Argentina
Published: October 2015

Hunter syndrome (mucopolysaccharidosis II) is a rare X-linked lysosomal storage disease caused by deficiency of the enzyme iduronate-2-sulfatase. The condition is one of a group of disorders, the mucopolysaccharidoses, which all result in accumulation of glycosaminoglycans. Hunter syndrome is a chronic progressive disorder whose clinical manifestations vary widely in severity and involve multiple organs and tissues. In addition to developing somatic symptoms, patients having the neuronopathic form of the disease also display developmental delay and cognitive impairment in early childhood that progressively worsens and that is severely life-limiting. Patients are at risk of developing secondary neurological manifestations, including hydrocephalus, vision and hearing loss, carpal tunnel syndrome and spinal cord compression. Common findings from brain magnetic resonance imaging (MRI) scans and at autopsy include neurodegenerative changes in white matter, the corpus callosum and basal ganglia; enlargement of periventricular spaces; ventriculomegaly; closed cephaloceles; and tissue atrophy. Though at present there is no specific treatment for the neurodegenerative aspects of the disease, hydrocephalus, carpal tunnel syndrome and spinal cord compression can be managed surgically. Patients who have Hunter syndrome should receive coordinated care from a multidisciplinary team: in light of the extensive neurological symptoms of the disease, neurologists play an important role in the diagnosis and management of this condition.
Identification and Functional Characterisation of von Willebrand Disease
Authors: Favaloro Emmanuel J ,   Professor, Department of Haematology, Institute of Clinical Pathology and Medical Research, Westmead Hospital, New South Wales
Published: October 2015

The identification and functional characterisation of von Willebrand disease (VWD) is challenging due to clinical uncertainty and limitations in test processes and panels used by laboratories, and because the classification scheme does not always permit unequivocal assignment of subtype. This article reviews contemporary alternatives to classic diagnostic approaches, including the incorporation of extended core test panels inclusive of the collagen-binding assay and the potential for desmopressin (DDAVP) challenge not only to provide therapeutic information but also to assist the better characterisation of individuals with defects or deficiencies in von Willebrand factor (VWF). Supplementary assays such as the PFA-100® and the VWF propeptide assay following DDAVP challenge are also worth considering.
Capturing Alloreactivity in Multiple Myeloma
Authors: Cook Gordon ,   Director, Blood and Marrow Transplantation Programme, Leeds Teaching Hospitals Trust, and Consultant Haematologist and Honorary Senior Lecturer, University of Leeds
Published: October 2015

Allogeneic stem cell transplantation (alloSCT) has been utilised in the management of both malignant and non-malignant haematological disorders for several decades and has established its role in producing long-term remissions. In the context of multiple myeloma (MM), compared with conventional therapies alloSCT induces the highest rate of remissions, resulting in long-term disease-free survival in over 30% of patients. However, it is associated with the highest rate of treatment-related mortality of all the interventions for MM. Following the introduction of new biological agents for the management of MM, the question of what role alloSCT has in MM is raised. This article aims to review where we are with alloSCT in MM, drawing from our experience thus far to plan the future role of alloSCT if we are to capitalise on a potential donor antimyeloma immune therapeutic effect.
Managing Anthracycline Extravasations and Protecting Tissue
Authors: Wengström Yvonne ,   Professor of Cancer Care, and Deputy Director, Research and Development, Cancer Care Research Centre, University of Stirling
Published: October 2015

Accidental leakage of a chemotherapy drug from the vein into the surrounding tissue can lead to severe and permanent disability. The degree of injury associated with an extravasation can range from a very mild skin reaction to severe necrosis, the severity of which relates to whether a drug binds to the DNA of the cell or not. The management of extravasations remains largely based on anecdotes of effective interventions that are based mostly on case studies, and healthcare professionals face the challenge of determining best practice based on a meagre body of evidence. However, recent advances in extravasation treatment are improving patient outcomes: the incidence of tissue necrosis can now be significantly reduced and, in some cases, prevented.
The German Breast Group – Healing Through Innovation, Competence and Partnership
Authors: Linder Mattea , Loibl Sibylle , Minckwitz Gunter von ,   Medical Research Fellow,   Department Leader, Medicine and Research,   Managing Director, German Breast Group Research Institute
Published: October 2015

The German Breast Group (GBG) is the leading breast cancer study group in Germany, conducting clinical trials in the adjuvant, neoadjuvant, preventative and palliative settings. One focus of the GBG is neoadjuvant studies, which have a long and successful history in Germany. The aim of neoadjuvant studies is to improve operability and to gain more information about the tumour itself in terms of the chemotherapy (invivo) as well as regarding the biology in general. However, preventative, palliative and adjuvant studies are also important components of the GBG. This article is an overview of the structure and working practice of the GBG and gives a sample of trials currently being led by the GBG.
The Epidemiology of Childhood Cancers
Authors: McNally Richard JQ ,   Director, Northern Region Young Persons’ Malignant Disease Registry, Institute of Health and Society, Newcastle University
Published: October 2015

In this article, the recent epidemiological literature on childhood cancer is reviewed. This includes findings from descriptive, case-control and cohort studies. The aetiology of most childhood cancers is unclear. Both genetic and environmental factors are likely to contribute. Increasing incidence, findings of clustering and seasonality in the incidence of certain cancers support a role for environmental agents in aetiology. The evidence concerning putative risk factors is considered and suggests that the aetiology is likely to be multifactorial and involve a number of different agents. These include infections, ionising radiation, certain chemical exposures, parental smoking, parental alcohol consumption and hair dyes. Conversely, breastfeeding and certain dietary supplements may convey protection. Recent findings regarding electromagnetic fields suggest that this factor is not likely to have a major role in aetiology.
Assessment of Thrombin Generation
Authors: Adams Murray J ,   Senior Lecturer in Haematology, School of Human Life Sciences, University of Tasmania
Published: October 2015

Thrombin plays a central role in haemostasis through both procoagulant and anticoagulant functions. Although measurement of thrombin generation in the laboratory has been possible for many years, recent advances in understanding a wider scope of physiological roles of thrombin as well as improvements in technology have resulted in methods that are less technically demanding and more reproducible. Consequently, thrombin-generation assays continue to be evaluated as a potentially useful laboratory method for determining haemostatic abnormalities, including both bleeding and thrombotic conditions, and for monitoring anticoagulant therapy. Despite these advances limitations still remain, including lack of standardisation between methods and the reporting of few large, well-designed studies, although this is likely to change in the next few years.
The Spectrum of T-cell and Natural Killer – Large Granular Lymphocytic Proliferations
Authors: Matutes Estella ,   Honorary Consultant Haematologist, Royal Marsden Hospital, and Reader, Institute of Cancer Research, London
Published: October 2015

Large granular lymphocyte (LGL) disorders comprise a spectrum of conditions that result from the expansion of a T cell or natural killer (NK) cell with a distinct morphology. The World Health Organization (WHO) considers T-cell LGL leukaemia as a distinct entity and chronic lymphoproliferative disorders (CLD) of NK cells as a provisional category. Patients are asymptomatic or manifest cytopenia, splenomegaly and autoimmune phenomena. Morphology, immunophenotype and molecular analysis are important diagnostic investigations. Most T-cell LGL leukaemias are T-cell receptor (TCR)-〈β+ LGL expansions displaying a CD8+ CD4- CD57+ or rarely a CD4+CD8±dim phenotype; a minority are clonal expansions of TCRγδ+LGL. NK LGL proliferations are CD3-, TCR-, CD16+, CD56+ with variable expression of T-cell non-specific markers. Expression of cytotoxic antigens T1A-1, granzymes and perforins are seen in both diseases. The pathogenesis is unknown. It is postulated that these disorders result from an expansion of a terminal memory-activated cytotoxic lymphocyte or an NK cell due to persistent antigenic stimulation with failure to undergo activation-induced cell death as a consequence of an impaired apoptotic pathway. Gene profiling has shown dysregulation of genes involved in apoptosis. The course is chronic, and transformation or aggressive disease is rare. Treatment strategies comprise immunomodulatory agents, purine analogues and antibody therapy.
Balancing the Efficacy and Tolerability of First-line Treatment in Elderly Myeloma Patients
Authors: Magarotto Valeria , Palumbo Antonio ,   Resident, Department of Haematology,   Chief, Myeloma Unit, Department of Oncology, Section of Haematology, University of Turin
Published: October 2015

Multiple myeloma (MM) is the second most frequent malignancy of the blood. It is more common among the elderly population, with <28% of patients 65–74 years of age and 37% >75 years of age. Before the introduction of novel agents, melphalan and prednisone (MP) was the best treatment for patients not eligible for autologous stem cell transplantation (ASCT). Steroids provide other options but with a higher toxicity, especially in elderly patients. Currently, the association of thalidomide with MP (MPT) represents the gold standard of treatment for patients ineligible for ASCT. Bortezomib and lenalidomide associated with MP provided effective and safe alternatives. High-dose dexamethasone combined with the new drugs is effective, but very toxic for elderly patients. Trials that combine low-dose dexamethasone with thalidomide, lenalidomide and bortezomib plus other agents such as doxorubicin and cyclophosphamide are ongoing. The role of transplantation is controversial in myeloma patients >65 years of age because elderly patients are fragile and the choice of therapy must take into account the likelihood of co-morbidities. Reducing the dose of the standard drug – eventually prolonging the duration of the treatment and administering prophylaxis – allows effective treatment of MM, without important or life-threatening toxicities.
Worldwide Use of Internet-based Survivorship Care Plans
Authors: Hill-Kayser Christine , Vachani Carolyn , Hampshire Margaret K , Metz James M ,   Assistant Professor, Department of Radiation Oncology,   Oncology Advanced Practice Nurse, Abramson Cancer Center,   Managing Editor, OncoLink, Abramson Cancer Center,   Associate Professor, and Vice Chair, Clinical Division, Department of Radiation Oncology and Associate Director, Clinical Services and Programs, Abramson Cancer Center, University of Pennsylvania School of Medicine
Published: October 2015

Over the past decade, the world has demonstrated an increased interest in and awareness of the unique needs of cancer survivors. Survivorship care plans are a communication tool intended to provide guidelines for the healthcare of survivors as they complete active cancer care, and for the duration of their lives. The Internet represents a unique way to communicate with cancer survivors, and data from several groups indicate that increasing numbers of survivors both desire information about their care and seek this information on the Internet. A handful of US-based groups have developed Internet-based tools for the creation of survivorship care plans. The first of these, the LIVESTRONG Care Plan (www.livestrongcareplan.org), is available via theOncoLinkcancer information website based at the University of Pennsylvania. Data from the first three years since the launch of this tool demonstrate increasing use by survivors from nearly every continent, with international users accounting for 16% of total users. Data from these users also demonstrate wide variability with regard to receipt of previous survivorship information and treatment summaries based on location of residence. This variation emphasises the vital role that Internet-based survivorship care plans may continue to play in the care of survivors worldwide.
Efficacy and Safety of Radioiodine in the Treatment of Disseminated Differentiated Thyroid Cancer in Children
Authors: Handkiewicz-Junak Daria , Kropinska Aleksandra ,   Assistant Professor and Head, Nuclear Medicine Unit,   Doctor, Department of Nuclear Medicine and Endocrine Oncology, Maria Skolowska  Curie Memorial Cancer Center and Institute of Oncology
Published: October 2015

Paediatric thyroid cancer is a rare disease, with well under 15% of all differentiated thyroid cancers (DTC) being diagnosed in childhood. Although DTC in paediatric patients frequently presents with metastases (6080% nodal and 1020% distant), the presence of metastases does not seem to negatively affect overall survival. The indolent nature of this disease together with its low incidence makes it difficult to determine optimum treatment strategies, which usually include surgery, radioiodine and thyroid hormone therapy. Although there is almost unequivocal agreement that total or near-total thyreoidectomy should be the initial treatment in childhood DTC, there are still many controversies about radioiodine application. This article discusses the key aspects of radioiodine treatment in DTC in children, with the emphasis on its benefits.
Maintenance Chemotherapy for Advanced Non-small-cell Lung Cancer
Authors: Gadgeel Shirish M ,   Associate Professor, Division of Hematology/Oncology, Department of Medicine, Barbara Ann Karmanos Cancer Institute, Wayne State University
Published: October 2015

Platinum-based combination chemotherapy, the current standard of care, enables modest improvements in survival and quality of life in patients with advanced non-small-cell lung cancer (NSCLC). In recent years, maintenance therapy in the form of either extended therapy or therapy with a different drug in patients deriving clinical benefit from initial treatment has been investigated. Extension of initial chemotherapy has shown improvements in time to tumour progression, but has not led to improved survival. Extension of chemotherapy is also associated with cumulative toxicities. Targeted agents such as bevacizumab and cetuximab can be extended until progression. However, the clinical benefits of continuing these agents until progression are unclear. Recently, a strategy of initiating treatment with a different drug following initial therapy has shown significant improvements in both progression-free survival and overall survival. Even though the applicability of this maintenance strategy may be limited to select patients, these data have established maintenance chemotherapy as a therapeutic option for advanced NSCLC patients.
The Newly Diagnosed Myeloma Patient – Therapeutic Approaches
Authors: San-Miguel Jesús ,   Professor of Medicine, and Head, Haematology Department, University Hospital of Salamanca
Published: October 2015

The outcome for myeloma patients has significantly improved over the last decade, mainly due to the introduction of new drugs with a singular mechanism of action such as thalidomide and lenalidomide (revlimid), both immunomodulatory drugs (IMIDs), and the proteasome inhibitor bortezomib (velcade). In newly diagnosed young patients, induction regimens such as bortezomib–thalidomide or lenalidomide plus dexamethasone will replace vincristine, doxorubicin and dexamethasone (VAD), followed by high-dose melphalan. Maintenance with IMIDs may represent the new standard of care for young multiple myeloma (MM) patients. This approach is being challenged by continuous treatment with novel agents and the postponement of a transplant until relapse. Allogeneic transplant should be conducted within the context of clinical trials. In elderly patients or non-transplant candidates, new regimens based on melphalan–prednisone plus thalidomide, velcade or lenalidomide have become new standards. The reduction of side effects while maintaining efficacy of treatment is most important in the elderly population.
Cetuximab in the Treatment of Locally Advanced Head and Neck Cancer
Authors: Knecht Rainald ,   Chairman, Ear, Nose and Throat Department and Clinic, University Medical Center Hamburg-Eppendorf
Published: October 2015

Locally advanced squamous cell cancer of the head and neck (LA SCCHN) includes various cancers of the oral cavity, pharynx and larynx that have spread from the primary site but have not metastasised. Due to poor public awareness of SCCHN and its symptoms, about 5070% of cases are diagnosed only when the disease has become locally advanced; prognosis by this time is poorer than during earlier stages. Combinations of chemotherapy with radiotherapy have produced greater efficacy in treating LA SCCHN over radiotherapy alone in various clinical trials, but this approach increases the incidence of toxicities. An alternative therapeutic approach is to use the monoclonal antibody cetuximab (Erbitux®). Cetuximab targets epidermal growth factor receptor (EGFR), which is overexpressed in LA SCCHN, and this overexpression of EGFR is associated with poor prognosis. A number of recent phase II and III clinical trials have demonstrated that cetuximab is an effective and safe treatment for LA SCCHN. One large phase III clinical trial demonstrated that the addition of cetuximab to radiotherapy in patients with LA SCCHN provides substantial efficacy and quality of life benefits, including improvements in overall survival, disease-free survival, response rate and European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 parameters, without markedly affecting safety and tolerability. Other, smaller phase II studies in patient populations having either resectable or non-resectable tumours have demonstrated the benefits of adding cetuximab to other chemotherapy/radiotherapy regimens for LA SCCHN. Cetuximab is currently the only targeted biological therapy approved for use in combination with radiation therapy for LA SCCHN. In conclusion, cetuximab represents a significant advance in the treatment of LA SCCHN. Furthermore, based on the data from the large phase III trial, the most recent European Society for Medical Oncology (ESMO) guidelines recommend the use of cetuximab in combination with radiotherapy in LA SCCHN.
Breast Magnetic Resonance Imaging of Multicentric, Multifocal and Bilateral Cancer — A Case-based Review
Authors: Dueñas Virginia Pérez , Gopegui Andreu María Ruíz de , Hodge Sara Morón , Manrique Asunción Suárez ,   Radiology Consultant, Department of Radiology, Hospital Universitario Madrid Sanchinarro,   Radiology Consultant, Department of Radiology, Hospital Infanta Elena, Hospital Universitario La Paz,   Doctor, Hospital Universitario La Paz,   Pathology Consultant, Hospital Universitario La Paz
Published: October 2015

Multifocal or multicentric breast cancer can be difficult to detect on mammography or ultrasound, particularly in patients with dense breast tissue. A multimodality approach that includes breast magnetic resonance imaging (MRI) is indicated, particularly when conservative surgery is being considered as it is the most sensitive technique for identifying additional sites of disease. However, its influence on recurrence and survival rates has yet not been clearly established, and false-positive cases may lead to more aggressive management and treatment. Radiologists should therefore be aware of relevant breast MRI findings. Infiltrating carcinomas, contralateral unsuspected carcinomas, occult carcinomas, false-positive cases and post-chemotherapy changes. Several cases of multiple-site breast carcinomas and their corresponding mammographic, ultrasound and MRI features have been reviewed for this article, in which the definition and differences between multifocal, multicentric and contralateral breast carcinoma are explained and the most relevant imaging findings on MRI are illustrated and correlated with mammogram and ultrasound findings. Finally, the role of breast MRI in the pre-operative assessment of breast cancer is discussed.
Inflammation and Thrombosis — Brothers in Arms
Authors: Faioni Elena M , Cattaneo Marco ,   Senior Researcher, Internal Medicine, Department of Medicine, Surgery and Dentistry, University of Milan,   Professor, Internal Medicine, University of Milan, and Director of Medicine III, San Paolo Hospital, Milan
Published: October 2015

Several interactions occur between inflammation and thrombosis that become more apparent with ageing. It is a two-way process: inflammation promotes aggregation and coagulation, while activated platelets and coagulation factors or peptides promote inflammation by several mechanisms. Recent evidence points to the role played by platelets and possibly coagulation factors in the regulation of innate immunity. Physiological anticoagulant pathways also have anti-inflammatory properties. This strong interdependence has an evolutionary origin. Current viewpoints are that inflammation, and thus coagulation, have a role in ageing. ‘Inflamm-ageing’ is a neologism that denotes a low-grade inflammation that accompanies healthy ageing, but can evolve towards excessive inflammation and clotting. It can thus be associated with thrombosis and early death. These fascinating pathophysiological discoveries provide novel targets for the development of new, potentially efficacious antithrombotic drugs.