bluuebunny/crossref_metadata_2025 huggingface dataset:
The Story of NAIMIT – A Framework 7 Project on Type 1 Diabetes
Authors: Mathieu Chantal , Overbergh Lut ,   Head of Endocrinology,   Senior Researcher, NAIMIT Consortium, Laboratory of Clinical and Experimental Endocrinology, KU Leuven, Leuven, Belgium
Published: June 2015

NAIMIT (acronym for Natural Immune Modulation for Intervention in Type 1 Diabetes) is a large-scale collaborative programme of the 7th framework from the European Commission. The aim of the consortium is to bring together a group of leading European researchers spanning the field from genetics, through pancreatic beta-cell, dendritic cells and T-cell biology, towards clinical interventions. The ultimate goal is to develop novel and personalised interventional therapies in recent-onset type 1 diabetic patients, with minimal immune system interference, leading to beta-cell protection and restoration, based on a solid understanding of the disease pathogenesis, enabling experimental findings to be adopted for clinical applications.
Skin Autofluorescence – A Non-invasive Measurement for Assessing Cardiovascular Risk and Risk of Diabetes
Authors: Stirban Alin , Heinemann Lutz ,   Director Endocrinology and Diabetes Complications,   Senior Scientific Consultant, Profil, Neuss, Germany
Published: June 2015

The results of the Diabetes Control and Complications Trial-Epidemiology of Diabetes Interventions and Complications (DCCT-EDIC) study have strengthened the ‘glycaemic memory’ concept, postulating that the quality of metabolic control over several years predicts the development of diabetic complications. To mirror long-term metabolic control, the degree of glycated haemoglobin (HbA1c) might not represent the optimal biomarker. Other substances with a longer persistence, like the so-called advanced glycation end-products (AGEs), which probably form the substrate of the glycaemic memory, might perform better. Newly developed methods such as the assessment of skin autofluorescence (SAF), enable fast, uncomplicated and non-invasive AGEs assessment. SAF was validated for diabetes screening and shows a good predictive value for the development of diabetic and cardiovascular complications. This article deals with the theoretical background and with available clinical data on this new variable.
Effectiveness of the Dexamethasone Intravitreal Implant for Treatment of Patients with Diabetic Macular Oedema
Authors: Medeiros Marco Dutra , Alkabes Micol , Nucci Paolo ,   Consultant Ophthalmologist – Vitreoretinal Surgeon, Central Lisbon Hospital Center, NOVA Medical School, Universidade NOVA de Lisboa, Lisbon, Portugal,   Consultant Ophthalmologist – Vitreoretinal Surgeon, University Eye Clinic, San Giuseppe Hospital, University of Milan, Milan, Italy,   Professor of Ophthalmology, University Eye Clinic, San Giuseppe Hospital, University of Milan, Milan, Italy
Published: June 2015

Diabetic macular oedema (DMO) is a leading cause of vision loss in the working-age population worldwide. Corticosteroid drugs have been demonstrated to inhibit the expression of both the vascular endothelial growth factor (VEGF) gene and other anti-inflammatory mediators, such as prostaglandins. Triamcinolone, fluocinolone and dexamethasone are the main steroids that have been studied for the treatment of macular oedema. Over the last few years, several studies have suggested an important role for dexamethasone in the management of DMO. The dexamethasone intravitreal implant (DEX implant) (Ozurdex®; Allergan, Inc., Irvine, CA) is a novel approach approved by the US Food and Drug Administration (FDA) and by the EU for the intravitreal treatment of macular oedema after branch or central retinal vein occlusion, and for the treatment of non-infectious uveitis affecting the posterior segment of the eye. We reviewed manuscripts that had investigated the pharmacokinetics, efficacy and safety of the DEX implant regarding DMO treatment.
Glucose Control and Cardiovascular Outcomes in Clinical Trials of Sodium Glucose Co-transporter 2 Inhibitor Treatments in Type 2 Diabetes
Authors: Oliveros Rene A , Pham Son V , Bailey Steven R , Chilton Robert J ,   Assistant Professor and Director, Cardiac Care Unit, Audie L Murphy VA Hospital, University of Texas Health Science Center at San Antonio,   Assistant Professor and Chief of Cardiology, Audie L Murphy VA Hospital, University of Texas Health Science Center at San Antonio,   Professor and Chief, Division of Cardiology, University of Texas Health Science Center at San Antonio,   Professor and Director, Catherization Lab, Audie L Murphy VA Hospital, University of Texas Health Science Center at San Antonio, San Antonio, Texas, US
Published: June 2015

Currently available medications for the treatment of type 2 diabetes have limitations, and many patients do not achieve glycaemic control. Recently, a new approach has emerged using sodium glucose co-transporter 2 (SGLT2) inhibitors that decrease glucose reabsorption in the kidneys, increasing urinary glucose excretion. These agents offer the potential to improve glycaemic control independently of insulin pathways while avoiding hypoglycaemia. Two drugs of this class, canagliflozin and dapagliflozin, have been approved by the US Food and Drug Administration (FDA); another, empagliflozin, has been filed for regulatory approval and several others are in advanced development. These drugs have been shown to effectively reduce blood glucose, fasting plasma glucose and glycated haemoglobin (HbA1C) levels in phase III clinical trials when used as monotherapy and as add-on therapy to other diabetes medications, including insulin. Another advantage of the SGLT2 inhibitors over existing treatments is the improvement in cardiovascular risk factors, particularly in terms of reductions in blood pressure and body weight. SGLT2 inhibitors have been generally well tolerated. While more long-term safety data are required to elucidate the benefit–risk profile of SGLT2 inhibitors, the rationale for their use in type 2 diabetes therapy is strong.
Management of Type 2 Diabetes – Methods for Addition of Prandial to Basal Insulin
Authors: Rodbard Helena W , Karolicki Boris ,   Medical Director, Endocrine and Metabolic Consultants, Rockville, Maryland, US,   Medical Director, Novo Nordisk Inc., Princeton, New Jersey, US
Published: June 2015

As glycaemic control deteriorates with the progression of type 2 diabetes, treatment guidelines advocate starting basal insulin therapy, and then progressing to a basal–bolus regimen as needed. Nevertheless, although timely intensification of therapy is important to minimise the risk of diabetic complications, considerable clinical inertia exists, not only in the initiation of insulin but also in the progression to multiple-dose insulin regimens. One barrier has been the lack of guidance about how to make the transition from basal-only to basal–bolus insulin therapy. In this review, we discuss how data from the recent FullSTEP study, along with other randomised studies, will help to bridge this gap. Prandial boluses can be added to basal insulin in a stepwise manner, using a straightforward, patient-led dose titration approach and simple estimation of which meal to add the initial prandial bolus to. Reducing the complexity of progression to multiple-dose insulin regimens and empowering patients will lessen the burden on clinicians, improve treatment satisfaction and facilitate timely implementation of treatment guidelines.
Energy Flux and its Role in Obesity and Metabolic Disease
Authors: Hand Gregory A , Blair Steven N ,   Professor, Department of Exercise Science,   Professor, Department of Exercise Science,   Department of Epidemiology and Biostatistics, University of South Carolina, Columbia, South Carolina, US
Published: June 2015

In order to reverse the global obesity pandemic, there is a need for an enhanced understanding of the energy dynamics that underlie the problem. To maintain a stable body weight, energy intake must, over time, match or equal energy expenditure, a concept known as energy balance. Obesity results from a positive state of energy balance (i.e. when energy intake exceeds energy expenditure). However, recent research suggests that strategies to combat obesity should focus on energy flux (the amount of calories going through a system), rather than energy balance alone. In other words, it is easier to maintain weight loss at higher levels of physical activity. Recent findings suggest that a high energy flux, maintained by increasing energy expenditure, can improve an individual’s metabolic profile without changing weight. Further understanding of this concept may help in the design of interventions to achieve and maintain a healthy weight.
What is Causing the Worldwide Rise in Body Weight?
Authors: Shook Robin P , Blair Steven N , Duperly John , Hand Gregory A , Matsudo Sandra M , Slavin Joanne L ,   Postdoctoral Researcher, Department of Exercise Science, Arnold School of Public Health, University of South Carolina, Columbia, South Carolina, US,   Professor, Departments of Exercise Science, Epidemiology, and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, South Carolina, US,   Associate Professor, Department of Internal Medicine, Universidad de los Andes Medical School, Bogotá, Colombia,   Professor, Department of Exercise Science, Arnold School of Public Health, University of South Carolina, Columbia, South Carolina, US,   Professor and Director General, Agita São Paulo Program-Studies Center, Physical Fitness Research Center for São Caetano do Sul, São Caetano do Sul, São Paulo, Brazil,   Professor, Department of Food Science and Nutrition, University of Minnesota, St Paul, Minnesota, US
Published: June 2015

The worldwide rise in body weight has reached epidemic proportions and this has serious public health consequences. Despite the universal recognition of this problem, its causes are still debated: some attribute it to excess caloric intake; others blame a lack of physical activity (PA); some implicate specific changes to micro- and macro-nutrients. During the past century, government health agencies have developed guidance on healthy eating. These, along with advances in agriculture and food manufacturing, have largely eliminated nutrient deficiencies and helped reduce the consumption of fat. Over the past 60 years, however, technological advances and shifts in the types of occupations prominent in industrialised as well as developing countries have resulted in well-documented decreases in energy expenditure. Energy intake must be balanced with energy expenditure in order to prevent weight gain, and there is increasing evidence that this balance must be at a relatively high level of energy flux. A programme that was started in São Paulo in 1996 known as ‘Agita’ has sought to motivate populations to engage in small amounts of physical exercise daily to tackle growing obesity levels. This multi-agency initiative is one example of how to successfully increase exercise within a community and scale both within (e.g. all states in Brazil) and across many nations. Reducing caloric intake in whole populations is challenging especially at relatively low levels of energy expenditure, and evidence suggests that there is a critical energy flux threshold for regulating intake to achieve energy balance. Increasing PA, however, may be more achievable than reducing intake. Activity raises caloric expenditure and can offset excess intake. The implementation of programmes to achieve greater PA is therefore vital if the worldwide rise in body weight is to be halted, while we also need to implement programmes to help people eat smarter.
Multikinase Inhibitors for the Treatment of Progressive, Metastatic Medullary Thyroid Cancer – An Evolving Paradigm
Authors: Jarzab Barbara , Krajewska Jolanta ,   Head of Nuclear Medicine and Endocrine Oncology Department,   Research Assistant, Nuclear Medicine and Endocrine Oncology Department, M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland
Published: June 2015

Medullary thyroid cancer (MTC) is an uncommon type of thyroid cancer, representing around 4 % of the all thyroid cancers, and is a challenging malignancy. So far, surgery has been the only curative treatment and until recently there have been no effective medications. Within the past 5 years, multi-targeted kinase inhibitors have emerged that have shown convincing efficacy against such tumours. These drugs have changed the landscape in MTC treatment by providing effective medication for the first time. The modes of action of these drugs differ, but most target RET, a tyrosine kinase shown to play an important role in the pathobiology of MTC, as well as other receptors including vascular endothelial growth factor receptors (VEGFRs), epidermal growth factor receptor (EGFR) and the hepatocyte growth factor receptor MET. Two agents in this class, vandetanib and cabozantinib, have demonstrated efficacy and safety in phase III trials and have consequently received regulatory approval. Other therapies for MTC treatment, including some with similar modes of action, are also in early development.
The Use of Denosumab in a Nonagenarian with Primary Hyperparathyroidism
Authors: Shalaby Tamer , Anandappa Samantha , Sivappriyan Siva , Kumar Jesse ,   Registrar in Acute Medicine and Endocrinology,   CT1 Endocrinology,   Consultant Endocrinologist, Maidstone Hospital, Maidstone, Kent, UK,   Consultant Endocrinologist, Maidstone Hospital, Maidstone, Kent, UK
Published: June 2015

Denosumab is a monoclonal antibody which is currently licensed in the UK drug market for the prevention of skeletal-related events secondary to malignancy (excluding myeloma). This monoclonal antibody is a 6 monthly subcutaneous injection that works by lowering calcium levels. When used in a 90 year old patient with primary hyperparathyroidism it demonstrated a dramatic reduction in the calcium level which had proven difficult to reduce by bisphosphonates and who was not a candidate for surgical intervention.
Primary Hyperparathyroidism Focused on Molecular Pathogenesis
Authors: Gómez Sáez José Manuel ,   Researcher, Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Hospital Universitario de Bellvitge, L´Hospitalet de Llobregat, Barcelona, Spain
Published: June 2015

Primary hyperparathyroidism (PHPT) is a common cause of hypercalcaemia. The most common lesion found in patients is the solitary benign parathyroid adenoma. Multiple parathyroid adenomas have also been reported. Parathyroid carcinomas are an uncommon cause of PHPT. In 15% of patients, all four parathyroid glands are involved and it may be associated with a familial hereditary syndrome, such as multiple endocrine neoplasia, types 1, 2A and 4. PHPT jaw tumour syndrome is associated with fibromas in the mandible and tumours can also be present in the kidneys and the uterus. No predisposing germline DNA variants in parathyroid adenomas have been demonstrated and only a few clonally altered genes that drive parathyroid tumorigenesis have been identified. Frequently parathyroid adenomas haveHRPT2gene mutations that are likely to be of pathogenetic importance. Mutations in theMEN1gene (localised to 11q13) are responsible for multiple endocrine neoplasia 1. Multiple endocrine neoplasia 2A, which can be associated with medullary thyroid cancer, is due to a germline mutation of theRETproto-oncogene located on chromosome 10. In MEN1-like negative patients some of the germline mutations in this new susceptibility gene were due to gene CDKN1B (12p13). This new syndrome was classified as multiple endocrine neoplasia 4. In PHPT jaw tumour syndrome,HRPT2, the gene on the long arm of chromosome 1, is responsible for the syndrome. It is suggested to perform genetic testing in patients with PHPT below the age of 30 years, but at any age in patients presenting with multigland parathyroid disease.
Impairment of Arterial Compliance in Cushing’s Syndrome
Authors: Bassareo Pier Paolo , Zedda Angela Maria , Mercuro Giuseppe ,   Chief of the Section of Paediatric Cardiology, Department of Medical Sciences ‘M Aresu’, University of Cagliari, Cagliari, Italy,   Specialist Registrar in Cardiology, Department of Medical Sciences ‘M Aresu’, University of Cagliari, Cagliari, Italy,   Professor of Cardiology, Department of Medical Sciences ‘M Aresu’, University of Cagliari, Cagliari, Italy and Medical Director of the Cardiology and Angiology Unit, University Hospital of Cagliari, Italy
Published: June 2015

Arterial stiffness may be useful for stratifying cardiovascular risk in individuals suffering from a number of pathologies, such as hypertension, diabetes, obesity, dyslipidaemia and coronary artery disease. Cushing’s syndrome is underpinned by a complex metabolic syndrome, which is potentially implicated in the onset of blood vessel alterations and the increase in arterial wall stiffness. The aim of this paper was to perform a review about the most important studies conducted in order to evaluate the arterial distensibility profile of subjects affected by Cushing’s syndrome. Increased arterial stiffness may persist even after successful cure of this disease. It is therefore of fundamental importance to identify the presence of early vascular alterations in these patients, in order to commence their treatment and thus attempt to prevent the subsequent onset of adverse cardiovascular events.
Equivalent Recombinant Human Insulin Preparations and their Place in Therapy
Authors: Sandow Juergen , Landgraf Wolfgang , Becker Reinhard , Seipke Gerhard ,   Professor, Centre of Pharmacology, Johann-Wolfgang-Goethe University, Frankfurt-Main, Germany,   Medical Affairs Diabetes Division,   Clinical Pharmacology Diabetes Division,   Chemistry and Biotechnology Development, Sanofi-Aventis, Frankfurt, Germany
Published: June 2015

Recombinant human insulin was one of the first products of biotechnology. It was developed in response to the need for a consistent and sufficient worldwide supply. Recombinant human insulin replaced the animal insulins and semisynthetic insulins obtained by modification of animal insulins. Bioequivalence studies were required for regulatory approval. Three reference products were independently established during these procedures: Humulin® (Eli Lilly and Co), Novolin® (NovoNordisk) and Insuman® (Sanofi). Numerous brand names have been used during the commercial development of recombinant human insulin formulations. In this review, three current brand names are used for consistent identification. Human insulin for Humulin and Insuman are produced by fermentation in bacteria (Escherichia coli) and for Novolin in yeast (Saccharomyces cerevisiae). The bioequivalence of recombinant human insulin products was investigated in euglycaemic clamp studies. An overview of such bioequivalence studies is provided here. This paper will consider the relevance of human insulin formulations today and their place in therapy.
Worldwide Coverage of Newborn Screening for Congenital Hypothyroidism— A Public Health Challenge
Authors: LaFranchi, MD Stephen H ,   Professor of Pediatrics, Division of Endocrinology, Oregon Health & Science University, Portland, Oregon, US
Published: June 2015

Despite the fact that programs began detecting neonates with congenital hypothyroidism (CH) over 40 years ago, at present only 30 % of the world birth population (approximately 127 million) undergoes screening for this disorder. The estimated cost of detection by screening, $15,400 compares with a lifetime expense of $1,296,000 in developed countries. The annual cost of the 30,000 CH cases not identified and treated early is approximately $40 billion dollars. Increasing the coverage of newborn screening worldwide remains a significant public health challenge.
Validation and Multicenter Clinical Experience of the Afirma® Gene Expression Classifier
Authors: Angell Trevor E , Alexander Erik K ,   Associate Physician, Brigham and Women’s Hospital; Instructor in Medicine, Harvard Medical School, US,   Chief, Thyroid Section, Brigham & Women’s Hospital; Associate Professor of Medicine, Harvard Medical School, US
Published: June 2015

The current assessment of clinically relevant thyroid nodules is imprecise and nonspecific, primarily due to the presence of indeterminate cytology. This cytologic category implies a low but clinically important risk for thyroid cancer, historically prompting consideration for diagnostic thyroidectomy in most patients. Over the last 5 years, novel molecular testing options have become available and appear able to modify preoperative thyroid cancer risk and better inform clinical decisions. The Afirma® gene expression classifier (GEC) measures messenger RNA (mRNA) expression patterns in fine-needle aspiration (FNA) tissue and seeks to identify a benign signature despite indeterminate cytology. When detected, the cancer risk is low and allows for prevention of unnecessary surgeries. The results of a large, multicenter, blinded validation trial of the Afirma GEC demonstrated the test’s high negative predictive value. Subsequent independent studies of the Afirma GEC in clinical use have documented the influence these results have on preoperative management recommendations. This review summarizes the current data regarding the Afirma GEC, including the original validation trial and recent multicenter clinical experience.
Diagnosis and Management of Acromegaly in 2014 (Update from 2012)
Authors: Katznelson, MD Laurence ,   Professor of Medicine and Neurosurgery, Stanford University, California, US
Published: June 2015

In this update to the 2012 summary, the current diagnostic and therapeutic approaches to acromegaly are reviewed. The goals of therapy are to control excess growth hormone (GH) secretion and tumor growth, and to limit, if not reverse, the long-term medical consequences and risk for premature mortality associated with acromegaly. Surgery is the preferred primary therapeutic option because it can lead to rapid reductions in GH levels and prevent mass effects from local tumor growth. Use of a somatostatin receptor ligand (SRL) preoperatively to improve surgical outcomes has not been substantiated. Medical therapy, including SRLs, dopamine agonists, and the GH receptor antagonist pegvisomant, is used most often in an adjuvant, secondary role for patients in whom surgery has been unsuccessful. Radiation therapy is most commonly recommended in the setting of failed surgery and lack of adequate control with medical therapy. A role of primary medical therapy forde novopatients has been proposed, particularly with SRLs. Using a multimodality approach, successful management of the disease and associated consequences should be achieved in the majority of subjects.
Insulin Glulisine in Pregnancy – Experience from Clinical Trials and Post-marketing Surveillance
Authors: Doder Zoran , Vanechanos Demi , Oster Manfred , Landgraf Wolfgang , Lin Stephen ,   Global Pharmacovigilance & Epidemiology, Sanofi, Bridgewater, New Jersey, US,   Global Pharmacovigilance & Epidemiology, Sanofi, Bridgewater, New Jersey, US,   Global Pharmacovigilance & Epidemiology, Sanofi, Bridgewater, New Jersey, US,   Medical Affairs, Diabetes Division, Sanofi-Aventis, Frankfurt, Germany,   Global Pharmacovigilance & Epidemiology, Sanofi, Bridgewater, New Jersey, US
Published: June 2015

Pregnancies complicated by gestational diabetes or pre-existing type 1 or type 2 diabetes mellitus are associated with a higher rate of adverse outcomes compared with pregnancies in the background population. These outcomes include miscarriage, pre-term delivery, pre-eclampsia, perinatal mortality and congenital malformations. Insulin glulisine (ApidraR, Sanofi) is a rapid-acting insulin analogue indicated for the treatment of adults, adolescents and children 6 years or older with diabetes mellitus where treatment with insulin is required. Here, all post-marketing and clinical trials safety data with insulin glulisine in pregnancy available to Sanofi up to June 2014 are summarised together with the findings of a comprehensive literature search. Cumulatively, a total of 303 pregnancy exposures to insulin glulisine were received. Of these 303 pregnancy exposures, there were 116 live births, 12 spontaneous abortions, two late foetal intra-uterine deaths (>28 weeks), three elective abortions and 170 cases without a known pregnancy outcome. There were six cases of congenital malformations; of these, there were five live births; in the other case a live birth was not confirmed. The congenital malformations reported to date do not reveal a pattern of defects. In conclusion, the evidence to date does not suggest a causal association between insulin glulisine and an increased risk of pregnancy complications or congenital malformations.
GLP-1 Receptor Agonists in Type 2 Diabetes and Beyond – New Insights 2015
Authors: Gallwitz Baptist ,   Deputy Chief, Department of Medicine IV; Head of the Outpatient Clinic for Diabetes and Endocrinology, Eberhard Karls University, Germany
Published: June 2015

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) were introduced for type 2 diabetes therapy nearly 10 years ago, among them short-acting compounds on the basis of the GLP-1-like peptide exendin-4 (exenatide and lixisenatide) and a long-acting GLP-1 RA based on the human GLP-1 sequence (liraglutide). Recently, two novel long-acting GLP-1 RAs on the basis of human GLP-1 sequence, for onceweekly application, have been approved for therapy of type 2 diabetes. Additionally, liraglutide has been approved for treatment of obesity at a higher dose than that used for diabetes therapy. This mini-review gives a short overview of the novel long-acting GLP-1 RAs albiglutide and dulaglutide and also reviews the studies of liraglutide in treatment of obesity leading to its approval for this use. These studies were largely presented at the annual meeting of the European Association for the Study of Diabetes (EASD) in fall 2014.
Early Vascular Ageing – A Concept in Development
Authors: Nilsson Peter M ,   Professor, Lund University, Malmö, Sweden
Published: June 2015

Cardiovascular disease (CVD) is a prevalent condition in the elderly, often associated with metabolic disturbance and type 2 diabetes. For a number of years, research dedicated to understand atherosclerosis dominated, and for many good reasons, this pathophysiological process being proximal to the CVD events. In recent years, research has been devoted to an earlier stage of vascular pathology named arteriosclerosis (arterial stiffness) and the new concept of early vascular ageing (EVA), developed by a group of mostly European researchers. This overview describes recent developments in research dedicated to EVA and new emerging aspects found in studies of families at high cardiovascular risk. There are new aspects related to genetics, telomere biology and the role of gut microbiota. However, there is still no unifying definition available of EVA and no direct treatment, but rather only recommendations for conventional cardiovascular risk factor control. New interventions are being developed – not only new antihypertensive drugs, but also new drugs for vascular protection – the selective angiotensin-II (AT2) agonist Compound 21 (C21). Human studies are eagerly awaited. Even new functional food products could have the potential to positively influence cardiometabolic regulation, to be confirmed.
Which One to Endorse Among the Multitude of Lipid Guidelines?
Authors: Sonmez Alper ,   Associate Professor in Medicine, Gulhane Military Medical Academy, School of Medicine, Department of Endocrinology and Metabolism, Ankara, Turkey
Published: June 2015

Dyslipidemia is the major risk factor for atherosclerotic cardiovascular diseases. A multitude of lipid guidelines exist, with several controversies, and the best approach in dyslipidemia management is not clear. The tools and lipoproteins used for risk assessment, whether to use a treatment target and implementing drugs other than statins are all controversial points. Until the time for the publication of an agreeable lipid guideline, physicians should choose their way by considering the advantages and disadvantages of the existing guidelines.
Cushing’s Disease – Quality of Life, Recurrence and Long-term Morbidity
Authors: Huguet Isabel , Ntali Georgia , Grossman Ashley , Karavitaki Niki ,   Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Headington, UK,   Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Headington, UK,   Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Headington, UK,   Centre for Endocrinology, Diabetes and Metabolism, School of Clinical and Experimental Medicine, University of Birmingham, UK
Published: June 2015

Cushing’s disease (CD) is a rare disorder caused by an adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma. Chronic exposure to hypercortisolism leads to significant morbidities, which may be only partially reversible after remission of the disease, as well as to impairment of the health-related quality of life (HRQoL) and an increase in mortality. Transsphenoidal surgery (TSS) is the treatment of choice, and recurrence rates vary widely, confirming the need for lifelong follow-up. This review summarises the studies performed on HRQoL, recurrence rates and morbidities in patients who have CD.
Current Challenges in the Management of Prolactinomas
Authors: Maiter Dominique ,   Head, Division of Endocrinology; Professor of Medicine, Department of Endocrinology and Nutrition Cliniques Universitaires Saint-Luc, Université catholique de Louvain, Brussels, Belgium
Published: June 2015

Although the diagnosis of prolactinoma is often straightforward and the treatment strategy has been well defined in recent guidelines, several challenging issues persist in their management. The differential diagnosis of a large pituitary tumour with moderately elevated prolactin (PRL) concentrations is sometimes difficult, and prolonged treatment with a dopamine agonist may be inappropriate when the diagnosis of a prolactinoma is not sufficiently well substantiated. Also, timely withdrawal of dopamine agonist treatment and the remaining indications of transsphenoidal surgery are still matters of debate. Last but not least, the management of resistant or aggressive prolactinomas remains a challenge for the clinician, especially when they occur in young patients
Sarcopenia in Endocrine Disorders – The Iceberg or Its Tip?
Authors: Minetto Marco A , Ghigo Ezio ,   Post-doc fellow,   Professor of Endocrinology; Director of the School of Medicine, University of Turin, Turin, Italy
Published: June 2015

Endocrine myopathies represent disorders of the musculoskeletal system that significantly impair the state of health. Sarcopenia is their pathophysiological common denominator. Recent reports have shown that endocrine disorders, even when subclinical, may also be associated with tendinopathies. It may thus be suggested that both hormones and hormonal disorders have complex actions on the musculoskeletal system and that musculoskeletal endocrinology represents a fascinating research area still awaiting exploration.
Assessing Osteoporosis in the Young Adult
Authors: Choong Wong Sze , Gallacher Stephen , Ahmed Syed Faisal ,   Honorary Consultant Paediatric Endocrinology, Developmental Endocrinology Research Group, School of Medicine, University of Glasgow, Glasgow,   Consultant Physician and Endocrinologist, Diabetes Centre, Southern General Hospital, Glasgow,   Consultant Paediatric Endocrinologist, Developmental Endocrinology Research Group, School of Medicine, University of Glasgow, Glasgow, UK
Published: June 2015

Osteoporosis in the young adult is a relatively rare phenomenon, and its diagnosis needs careful assessment of the affected person. The emphasis in the assessment of bone health is gradually shifting from a simple quantitative assessment of bone mineral density to one that includes bone quality. This may be particularly important in the young adult, where the aetiological cause of osteoporosis may be a primary genetic condition or secondary to another chronic condition.
Central Precocious Puberty – Management and Long-term Outcomes
Authors: Léger Juliane ,   Assistance Publique-Hôpitaux de Paris, Hôpital Robert Debré, Service d’Endocrinologie Diabétologie Pédiatrique, Centre de Référence des Maladies Endocriniennes Rares de la Croissance, F-75019 Paris, France,   Université Paris Diderot, Sorbonne Paris Cité, F-75019 Paris, France,   Institut National de la Santé et de la Recherche Médicale (Inserm), Unité 1141, DHU Protect, F-75019 Paris, France
Published: June 2015

Central precocious puberty (CPP) results from premature re-activation of the gonadotropic axis. CPP is much more common in girls than in boys and is idiopathic in most cases. In boys, precocious puberty is more likely to be linked to hypothalamic lesions (≈40%). Recent studies have implicated the inactivation ofMKRN3gene in ‘idiopathic’ CPP. Gonadotropin-releasing hormone agonists are the standard treatment for progressive CPP.
Why Early Diagnosis Is Better for Alzheimer’s Patients
Authors: Voisin Thierry , Sourdet Sandrine , Delrieu Julien , Vellas Bruno ,   Alzheimer’s Disease Clinical Research Centre, Gerontopôle, Toulouse University Hospital,   INSERM U 558, Toulouse,   Alzheimer’s Disease Clinical Research Centre, Gerontopôle, Toulouse University Hospital,   INSERM U 558, Toulouse,   Alzheimer’s Disease Clinical Research Centre, Gerontopôle, Toulouse University Hospital,   INSERM U 558, Toulouse,   Alzheimer’s Disease Clinical Research Centre, Gerontopôle, Toulouse University Hospital,   INSERM U 558, Toulouse
Published: June 2015

Alzheimer’s disease (AD) is the most common cause of dementia. AD progression leads to a significant deterioration in cognitive function, resulting in a significant impact not only on patient quality of life but also on the quality of life of family members/care-givers. Some physicians do not feel that diagnosing AD is necessary due to the absence of any cure and the stress related to diagnosis. Nevertheless, it is important to diagnose AD as early as possible. Early diagnosis of AD allows the patient to be more involved in treatment planning, since at this stage the patient’s cognitive function will be near normal. Many forms of the disease do not progress rapidly, and early diagnosis and treatment will allow a good quality of life for the patient, family members and care-givers. The general practitioner has a special role in detecting and following up patients diagnosed with AD.
Are Biomarkers Valid as Surrogates for Treatment Effects in Alzheimer’s Disease?
Authors: Scheltens Philip ,   Professor, and Director, Alzheimer Centre, VU Medical Centre
Published: June 2015

Diagnosis of Alzheimer’s disease (AD), the most common form of dementia, involves neuropsychological testing, limited laboratory tests and brain imaging. Current therapeutic options for AD are symptomatic treatments that target dysfunctional neurotransmitters associated with the disorder. Recent research has focused on therapeutic strategies that inhibit the production and aggregation of amyloid beta protein (Aβ) in plaques and increase its clearance from the brain. Such strategies are likely to be most effective at pre-clinical stages of the disease, before widespread synaptic and neuronal loss occurs. Thus, there is a need for biomarkers that predict disease course and outcome and monitor disease progression and treatment efficacy. The development of such biomarkers for AD is critical to translating the efficacy of new therapies.
Non-motor Symptoms in Parkinson’s Disease
Authors: Antonini Angelo ,   Physician, Parkinson Institute, Milan, Medical Co-ordinator for Information Technology and Clinical Research, Department of Neuroscience, Hospital ‘Istituti Clinici di Perfezionamento’, Milan, and Professor of Neurology, University of Milan-Bicocca
Published: June 2015

Parkinson’s disease (PD) is the second most common neurodegenerative disorder after Alzheimer’s disease and is responsible for significant morbidity and costs. Non-motor manifestations of PD can be as disabling as the classic motor symptoms. Moreover, medications used to treat PD motor symptoms may have variable effects on these non-motor domains.
Apomorphine in the Treatment of Parkinson’s Disease
Authors: Katzenschlager Regina ,   Consultant Neurologist, Department of Neurology, Danube Hospital, Social Medical Centre East, Vienna
Published: June 2015

The majority of patients with Parkinson’s disease (PD) develop motor fluctuations and dyskinesias as their condition progresses. In patients where adjustments of oral (or transdermal) treatment options can no longer adequately control these motor complications, further options include deep-brain stimulation for a minority of selected patients, intrajejunal levodopa (L-dopa) application via a pump or apomorphine infusion therapy. The dopamine agonist apomorphine provides relief from off periods when administered as a subcutaneous injection. When applied continuously via a portable pump system, oral medication can often be reduced considerably and dyskinesias improve in many patients.
Redressing the Balance in Parkinson’s Disease Management with a Greater Focus on Non-motor Symptoms and Care-giver Health
Authors: Lindvall Susanna , Lökk Johan , Wainwright Michael ,   Vice President, European Parkinson’s Disease Association (EPDA),   Senior Lecturer, Institute of Neurobiology, Care Sciences and Society, Karolinska Institute,   Medical Writer, Uppsala Science Park
Published: June 2015

A more widespread use of questionnaires and scales such as non-motor symptoms (NMS)-Quest and the non-motor symptoms scale (NMSS) has confirmed that NMS, such as sleeping difficulties and speech problems, are at least as troublesome for Parkinson’s disease patients as the major motor symptoms. These NMS can have a profound negative effect on patient quality of life and on the health of the person providing care. This fact is now receiving more attention in clinical practice and measures are being taken to improve the recognition and treatment of NMS, and to provide better support for care-givers. As our knowledge base of NMS expands, we are increasingly finding that some of them, e.g. olfactory deficit and rapid eye movement (REM) sleep behaviour disorder, also occur early in Parkinson’s disease, possibly pre-dating a diagnosis based on motor signs alone.
Population-based Studies on the Clinical Progression of Motor and Non-motor Features in Parkinson’s Disease
Authors: Alves Guido , Larsen Jan Petter ,   Norwegian Centre for Movement Disorders, and Department of Neurology, Stavanger University Hospital,   Norwegian Centre for Movement Disorders, and Department of Neurology, Stavanger University Hospital
Published: June 2015

Although Parkinson’s disease (PD) is a movement disorder in which tremor, rigidity and bradykinesia constitute the cardinal signs of the disease, it is increasingly recognised to be associated with a wide range of motor and non-motor features. Population-based studies demonstrate that the motor course in PD is generally slowly progressive, with average annual progression rates of ≤3%. However, there is remarkable inter-individual variation in the clinical course of PD, with advanced age and predominant postural instability and gait difficulties being major risk factors for more rapid motor and cognitive decline. Around 20–40% of patients exhibit subtle cognitive deficits at diagnosis. These usually worsen over time and progress into dementia, which approximately 80% of PD subjects develop during the course of their disease. Population-based studies indicate rather high frequencies of other non-motor symptoms in moderate to advanced stages, such as depression, fatigue, apathy, sleep disorders and autonomic dysfunction, although prevalence rates often are lower than those observed in clinic-based studies. However, as several population-based studies were cross-sectional, uncontrolled and did not use currently accepted rating scales or diagnostic criteria, the relative risk and clinical course of many disease-related features remain unclear in the general PD population. Further population-based studies are warranted in order to extend current knowledge on the clinical course in representative PD cohorts.
Genetic Susceptibility to Primary Intracerebral Haemorrhage
Authors: Dardiotis Efthimios , Dardiotis Efthimios , Xiromerisiou Georgia , Paterakis Konstantinos , Fountas Kostas , Hadjigeorgiou Georgios M ,   Laboratory of Neurogenetics, Department of Neurology, University of Thessaly, University Hospital of Larissa,   Institute of Biomedical Research and Technology, CERETETH, Larissa,   Laboratory of Neurogenetics, Department of Neurology, University of Thessaly, University Hospital of Larissa,   Institute of Biomedical Research and Technology, CERETETH, Larissa,   Laboratory of Neurogenetics, Department of Neurology, University of Thessaly, University Hospital of Larissa,   Institute of Biomedical Research and Technology, CERETETH, Larissa,   Department of Neurosurgery, University of Thessaly, University Hospital of Larissa,   Department of Neurosurgery, University of Thessaly, University Hospital of Larissa,   Laboratory of Neurogenetics, Department of Neurology, University of Thessaly, University Hospital of Larissa,   Institute of Biomedical Research and Technology, CERETETH, Larissa
Published: June 2015

Primary intracerebral haemorrhage (PICH) originates from the spontaneous rupture of cerebral arteries as a result of chronic degenerative alterations. Although the aetiology of PICH has not been fully elucidated, it may be the result of an interaction between genetic and environmental risk factors. Several genetic association studies have been conducted in patients with PICH with both positive and negative results. Most of them investigated the role of mutations in genes affecting the lipid metabolism, the coagulation processes, the inflammation and the regulation of blood pressure. In this article we briefly discuss the majority of these studies reporting the susceptibility genes that have been implicated in PICH.
Measurement of Optic Nerve Sheath Diameter for the Assessment of Risk of Raised Intracranial Pressure
Authors: Geeraerts Thomas , Menon David K , Benhamou Dan ,   AP-HP, University of Paris – South, Department of Anaesthesia and Critical Care, University Hospital Bicêtre,   Department of Anaesthesia, Addenbrooke’s Hospital and University of Cambridge,   Department of Anaesthesia, Addenbrooke’s Hospital and University of Cambridge,   AP-HP, University of Paris – South, Department of Anaesthesia and Critical Care, University Hospital Bicêtre
Published: June 2015

Raised intracranial pressure (ICP) is associated with poor outcome after brain injury, but is difficult to detect without invasive devices. As a part of the central nervous system, the optic nerve is surrounded by a dural sheath, and the subarachnoid space surrounding the optic nerve is subject to the same pressure changes as the intracranial compartment. Distension of the optic nerve sheath reflects an increase in cerebrospinal fluid (CSF) pressure and can be used to estimate the risk of raised ICP. Ocular sonography or brain magnetic resonance imaging (MRI) enables valid measurement of the distension of the dural sheath surrounding the optic nerve. An optic nerve sheath diameter greater than 5.8mm is likely to be associated with raised ICP. This non-invasive estimate of ICP may detect patients at risk, help make decisions regarding the placement of invasive ICP devices and allow the selection of patients for transfer to specialist centres.
The SH2D2A Gene -Contributions to Our Future Understanding of Multiple Sclerosis
Authors: Spurkland Anne , Sørensen Per Soelberg ,   Professor, Institute of Basal Medical Sciences, University of Oslo,   Professor of Neurology, Danish Multiple Sclerosis Research Centre, Department of Neurology, Copenhagen University Hospital, Rigshospitalet
Published: June 2015

TheSH2D2Agene encodes the T-cell-specific adapter protein (TSAd), which is involved in multiple signalling pathways, including those of the T-cell receptor, the vascular growth factor receptor 2 and the chemokine receptor CXCR4.SH2D2Ais preferentially expressed in activated T cells, natural killer (NK) cells and endothelial cells. A major function of TSAd seems to be to modulate Src kinase activity within the cell. TheSH2D2Agene as well as its gene region have been implicated in genetic susceptibility to autoimmune disease in both humans and mice. In this article, the current status of knowledge of theSH2D2Agene and its implications for our future understanding of multiple sclerosis are discussed.
Chronic Inflammatory Demyelinating Polyradiculoneuropathy - An Overview of Intravenous Immunoglobulin Therapy
Authors: Bril Vera ,   Division of Neurology, University Health Network, Toronto
Published: June 2015

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a significant source of disability, and early diagnosis and immunomodulatory therapy administration are critical to minimise disease progression and axonal degeneration. Intravenous immunoglobulin (IVIg) therapy is considered to be a first-line treatment for CIDP. Comparative short- and long-term data of IVIg versus corticosteroids in CIDP patients are limited. Of the five published placebo-controlled studies in CIDP, four reported only on short-term improvements in disability (≤6 weeks). However, the IGIV CIDP Efficacy (ICE) study, the largest randomised, placebo-controlled CIDP study published to date (n=117), reported significant improvements in disability, functional impairment and quality of life with IVIg (Gamunex®) 1g/kg maintenance therapy every three weeks for up to 48 weeks. Furthermore, long-term IVIg administration was safe and well tolerated, particularly given the short duration of the infusions. Data suggest that a long-term scheduled maintenance regimen of IVIg in appropriate patients may provide substantial benefit and reduce the risk of CIDP relapse.
Seizure Semiology, Neurotransmitter Receptors and Cellular-stress Responses in Pentylenetetrazole Models of Epilepsy
Authors: Bidmon Hans-J , Speckmann Erwin-J , Zilles Karl J ,   C & O Vogt Institute for Brain Research, Heinrich Heine University, Düsseldorf,   Institute of Physiology I, Westfälische Wilhelms University, Münster,   C & O Vogt Institute for Brain Research, Heinrich Heine University, Düsseldorf,   Institute for Neuroscience and Medicine INM2, Research Centre, Jülich,   Jülich Aachen Research Alliance, Research Centre
Published: June 2015

Ongoing research has elucidated a large variety of genes, proteins and enzyme products that are affected in epilepsy. Despite the pharmacological advances achieved by the development of antiepileptic drugs, numerous patients become pharmacoresistant. Therefore, animal models addressing these complex interactions among compensatory gene-expression cascades and consecutive molecular mechanisms are still a necessity for research-based gene and pharmacotherapy. In this article, we focus on pentylenetetrazole models to study the consequences of tonic–clonic seizures. We address two complex and closely linked aspects: alterations in neurotransmission and oxidative-stress responses. Reviewing just these two aspects highlights the need for a more standardised use of animal models and methods to allow a better integration of data from different lines of research. The latter will be most applicable for the understanding of complex disease-related interactions of gene networks, proteins and enzyme products and timely, research-based development of future therapeutic options.